Αρχειοθήκη ιστολογίου

Πέμπτη 21 Φεβρουαρίου 2019

The neuroplastic effect of olfactory training to the recovery of olfactory system in mouse model

Background

Several studies have reported the benefits of olfactory training (OT) in the olfactory nervous system of mouse models. Therefore, in this study we performed next‐generation sequencing to evaluate the effects of OT on mRNA sequencing in the olfactory area.

Methods

Mice in each group were administered 300 mg of 3‐methylindole per kilogram of mouse weight. The olfactory function was evaluated by a food‐finding test once a week. The olfactory neuroepithelium was harvested for histologic examination and protein analysis. Subsequently, data analysis, gene ontology and pathway analysis, quantitative real‐time polymerase chain reaction of mRNA, and Western blot analysis were conducted.

Results

Mice were divided into 4 groups according to treatment. Control, anosmia, training, and steroid group mice resumed food finding. Olfactory Maker Protein, olfr1507, ADCY3, and GNAL mRNA expression was higher in the olfactory neuroepithelium of OT than anosmia group mice. In total, 26,364 mRNAs were analyzed. Comparison of the results of OT vs anosmia revealed that ADCY8,10, GFAP, NGF, NGFR, GFAP, and BDNF mRNAs were upregulated in the gene ontology.

Conclusion

OT improved olfactory function, as indicated by the food‐finding test. OT improved the olfactory recovery time to stimulate olfactory nerve regeneration. OT may initially stimulate the olfactory receptor, followed by neurogenesis. Steroid therapy and OT operated under completely different mechanisms in the upregulated gene study. These results indicate that OT may be one of the future modalities for treating olfactory impairment.



https://ift.tt/2Eq6C6t

Clinical Guidelines on Chronic Rhinosinusitis in Children

Abstract

Purpose of Review

Pediatric chronic rhinosinusitis (CRS) is a prevalent problem that can elude diagnosis. In addition, given the burgeoning interest in pediatric sinonasal disease, treatment modalities are constantly evolving.

Recent Findings

The diagnosis of pediatric CRS is primarily based on clinical history and signs supported by objective findings (i.e., nasal endoscopy and/or computed tomography (CT) imaging). Cultures are indicated in patients who have not responded to medical therapy or have significant comorbidities. Nasal saline irrigation, nasal saline spray, and oral antibiotics are currently recommended for initial medical management. In children with CRS who have failed medical therapy, a stepwise approach to surgical intervention can lead to significant improvements in quality of life.

Summary

This review provides an overview of the current guidelines and recent literature regarding the diagnosis, microbiology, and treatment options of CRS in the pediatric population.



https://ift.tt/2Xg5CJo

Precision Medicine in Rhinosinusitis

Abstract

Purpose of Review

Our scope is the presentation of research and clinical progresses in relation to precision medicine that are expected to alter our clinical practice in relation to chronic rhinosinusitis (CRS). Current knowledge on phenotypes and endotypes, biomarkers, and clinical markers for diagnosis, medical and surgical therapy, and prognosis is presented as well as the role of precision medicine in United Airway Disease and SCUAD (severe-uncontrolled chronic upper airway inflammation).

Recent Findings

Current technological progresses, mostly in relation to molecular biology and information technology, have permitted more detailed pathophysiological assessments and multidimensional approaches in airways diseases. Based on the concept of united airways diseases, new classification schemes, called endotypes, have been proposed for CRS. In addition, novel biological treatments that have been introduced for the treatment of asthma show great promise as well for severe uncontrolled cases of CRS with nasal polyps. Central to this approach are new biomarkers that are being examined in relation to complex bio-clinical traits of CRS.

Summary

As this narrative review of the aforementioned precision medicine initiatives in relation to CRS advances, a modification of current practice is expected not only for severe chronic upper airways diseases in tertiary centers but also for milder and more common cases that are being encountered in the community.



https://ift.tt/2GWGIc3

Hypoallergenic Proteins for the Treatment of Food Allergy

Abstract

Purpose of Review

Food allergy is a growing health problem worldwide that impacts millions of individuals. Current treatment options are limited and strict dietary avoidance remains the standard of care. Immunotherapy using whole, native allergens is under active clinical investigation but harbors the risk of severe side effects including anaphylaxis. Newer food-specific therapies with hypoallergenic proteins may potentially offer safer treatment alternatives, and this review seeks to investigate the evidence supporting the use of these modalities.

Recent Findings

The utilization of different methods to alter allergen structure and IgE binding leads to reduced allergenicity and decreases the risk for systemic reactions, making the use of potential therapies including extensively heated egg/milk, peptide immunotherapy, recombinant allergen immunotherapy, and DNA vaccines safe and possibly efficacious forms of treatment in food allergy. However, for the majority of these treatment modalities, limited data currently exists looking at the safety and efficacy in human subjects with food allergy.

Summary

This review provides a comprehensive overview of the current evidence examining the safety and efficacy of hypoallergenic proteins in the treatment of food allergies.



https://ift.tt/2BNKIbr

Clinical Guidelines on Chronic Rhinosinusitis in Children

Abstract

Purpose of Review

Pediatric chronic rhinosinusitis (CRS) is a prevalent problem that can elude diagnosis. In addition, given the burgeoning interest in pediatric sinonasal disease, treatment modalities are constantly evolving.

Recent Findings

The diagnosis of pediatric CRS is primarily based on clinical history and signs supported by objective findings (i.e., nasal endoscopy and/or computed tomography (CT) imaging). Cultures are indicated in patients who have not responded to medical therapy or have significant comorbidities. Nasal saline irrigation, nasal saline spray, and oral antibiotics are currently recommended for initial medical management. In children with CRS who have failed medical therapy, a stepwise approach to surgical intervention can lead to significant improvements in quality of life.

Summary

This review provides an overview of the current guidelines and recent literature regarding the diagnosis, microbiology, and treatment options of CRS in the pediatric population.



https://ift.tt/2Xg5CJo

Multimorbidities of Pediatric Allergic Rhinitis

Abstract

Purpose of Review

Most children and adolescents with allergic rhinitis (AR) present extra-nasal multimorbid conditions, including conjunctivitis, asthma, atopic dermatitis, rhinosinusitis, or seromucous otitis. Additionally, they may present nasal obstructive disorders, such as septal deformity, turbinate enlargement, and adenoidal hyperplasia, which worsen nasal symptoms, especially nasal obstruction. This is a narrative review on the current state of the concomitant presence of AR and one or more multimorbidities.

Recent Findings

The presence of AR and one or more accompanying multimorbidities is associated to a higher severity and duration of the disease, a negative impact on quality of life, with worse control and lack of improvement with medical treatment. Therefore, AR needs to be managed with a multidisciplinary collaborative approach.

Summary

Pediatric AR needs to be considered in the context of a systemic disease, which requires a coordinated therapeutic strategy.



https://ift.tt/2txq4rq

Hypoallergenic Proteins for the Treatment of Food Allergy

Abstract

Purpose of Review

Food allergy is a growing health problem worldwide that impacts millions of individuals. Current treatment options are limited and strict dietary avoidance remains the standard of care. Immunotherapy using whole, native allergens is under active clinical investigation but harbors the risk of severe side effects including anaphylaxis. Newer food-specific therapies with hypoallergenic proteins may potentially offer safer treatment alternatives, and this review seeks to investigate the evidence supporting the use of these modalities.

Recent Findings

The utilization of different methods to alter allergen structure and IgE binding leads to reduced allergenicity and decreases the risk for systemic reactions, making the use of potential therapies including extensively heated egg/milk, peptide immunotherapy, recombinant allergen immunotherapy, and DNA vaccines safe and possibly efficacious forms of treatment in food allergy. However, for the majority of these treatment modalities, limited data currently exists looking at the safety and efficacy in human subjects with food allergy.

Summary

This review provides a comprehensive overview of the current evidence examining the safety and efficacy of hypoallergenic proteins in the treatment of food allergies.



https://ift.tt/2BNKIbr

Giant cell tumour of the scapula treated by partial scapulectomy

Giant cell tumour is a benign, but locally aggressive tumour. It most commonly affects the epiphysial-metaphyseal region of long bones, but rarely in flat bones. We present you a case of 26-year-old man with a large giant cell tumour of the inferior angle of the scapula. The patient was treated with partial scapulectomy with complete resection of tumour. There was excellent retention of shoulder function postoperatively.



https://ift.tt/2XeLdnT

Neurosyphilis presenting as cranial nerve palsy, an entity which is easy to miss

Neurosyphilis is a rare disease that until the 2000s was almost eradicated due to population awareness of HIV and efficient treatment. Since then, the prevalence of the entity is rising due to risk-associated behaviour such as unprotected intercourse. Neurosyphilis is still a difficult entity to diagnose especially when combined with acute HIV infection which can influence the usual clinical course of disease. In rare occasions, both acute HIV and early syphilis infection can present as mono or multiple cranial nerve palsies. This case demonstrates a rare manifestation of misdiagnosed early syphilis infection combined with acute HIV infection in a 34-year-old man with prior history of unprotected sex with men.



https://ift.tt/2Xh32mp

Resistant dermatomyositis in a rural indigenous Maya woman

A 28-year-old indigenous Guatemalan woman presented with 7 months of progressive weakness and numerous dermatological findings. She initially sought care within the free government-run health system and was treated with oral steroids for presumed dermatomyositis. Her symptoms progressed, including severe dysphagia, hypophonia and weakness preventing sitting. She was lost to follow-up in the public system due to financial and cultural barriers. A non-governmental organisation tailored to the needs of Maya patients provided home intravenous pulse dose methylprednisolone in the absence of first-line biologicals. With longitudinal home-based care, she achieved symptom free recovery. The rising burden of chronic non-communicable diseases highlights shortcomings in health systems evident in this case, including lack of provider capacity, limited infrastructure to test for and treat rare diseases and poor continuity of care. We provide potential solutions to help care delivery in low-resource settings adapt to the demans of chronic disease control with particular attention to social determinants of health.



https://ift.tt/2SlrLSI

Bilateral acute non-obstructive pyelonephritis presenting as acute kidney injury requiring haemodialysis

A 54-year-old female patient with hypothyroidism and diabetes mellitus type 2 was brought to emergency room by the family members for acute change in mental status. The laboratory evaluation demonstrated findings consistent with acute renal failure (normal renal function 3 months prior to presentation). She was initiated on hemodialysis due to lack of improvement in renal function. Urine culture done prior to initiation of antibiotics was positive for Escherichia coli, which was later confirmed by renal biopsy. Extensive workup for the cause of renal failure including for connective tissue disease, plasmacytoma, obstruction was negative. She was treated with 6 week course of antibiotics with eventual recovery of her renal function in 4 months.



https://ift.tt/2XfFYUW

Unknown primary Merkel cell carcinoma with cutaneous spread

The authors present the case of a woman in the seventh decade of life with medical history of: left nephrectomy for renal tuberculosis and non-Hodgkin's lymphoma treated with chemotherapy (QT) and radiotherapy. She presented with a 2-month history of non-tender, left inguinal lymph node enlargement. Positron Emission Tomography (PET)—CT —scanshowed hypermetabolic inguinal and retroperitoneal lymphadenopathies, no primary tumour. On the second dermatological examination a pink, 2 cm plaque on the anterior left knee was noted. The histopathological analysis revealed Merkel cell carcinoma. The patient underwent two lines of systemic QT, with life-threatening toxicities limiting treatment. Followed overwhelming disease progression with lymphoedema and numerous skin metastases in the left lower limb. The patient received palliative care until death. The rare incidence of such neoplasia and its uncommon clinical presentation justifies reporting this case and highlights the importance of multidisciplinary teams in the management of cancer patients.



https://ift.tt/2SjNQBc

Use of home telemedicine for critical illness rehabilitation: an Indian success story

One-fifth of healthcare beneficiaries in developed nations get discharged from hospitals to physician supervised skilled nursing care facilities. In low-income and middle-income countries like India, postdischarge skilled nursing facilities are at a very nascent stage and largely underequipped in terms of infrastructure, skilled nursing and physician staff to manage complicated patients. Hence the responsibility of management of such patients lies largely with their families. We present a case where a 26-year-old man with Duchenne Muscular Dystrophy who became ventilator dependent following major surgeries was weaned off his ventilator and rehabilitated back to his prehospital state. This was done at his home with visiting nurses and rehabilitation services under telemedicine supervision by a critical care specialist. Use of telemedicine services could be a viable and cost-effective option to ensure adherence to evidence-based medicine and standardisation of care in resource limited countries such as India.



https://ift.tt/2Sj48u9

Brentuximab vedotin in combination with sequential procarbazine, cyclophosphamide and prednisolone for the management of Hodgkins lymphoma-associated vanishing bile duct syndrome (VBDS) with severe obstructive liver failure

We present a novel treatment protocol that was successful in the management of Hodgkin's-associated vanishing bile duct syndrome, a rare but serious complication of Hodgkin's lymphoma. We believe that publication of this treatment protocol and the rationale for its development will be of interest to anyone faced with treating this challenging condition.



https://ift.tt/2Xc3GSd

Iatrogenic adrenal suppression following caudal epidural and facet joint injection

Caudal epidural injections and facet joint injections using steroids and local anaesthetic are widely used methods of pain control in patients suffering from radicular leg pain. In the vast majority of cases this is low risk. We present an interesting case of a patient who suffered from symptomatic adrenal suppression following a caudal epidural injection, and thus wish to draw this rare but significant complication to the attention of orthopaedic practitioners.



https://ift.tt/2SjbD45

Scrotal necrosis and no Fourniers in sight: a rare case of juvenile gangrenous vasculitis

Juvenile gangrenous vasculitis of the scrotum is a rare entity, of which to our knowledge we describe the first documented case in the UK. It follows a typical disease course, demonstrated by an 18-year-old male who presented with three necrotic scrotal lesions; proceeded by 3 days of fever, pharyngitis and lethargy. Previous cases have been managed successfully with systemic steroids. On this occasion, surgical debridement was made of the necrotic areas under antibiotic cover and complete resolution was achieved with excellent wound healing and no evidence of recurrence. This case report discusses the importance of disease recognition and the merits of surgical management. We also add to the debate as to whether this disease is a variation of pyoderma gangrenosum or a distinct entity itself within the pantheon of scrotal gangrene.



https://ift.tt/2XdBuOK

Drug-induced paraspinal myositis mimicking acute bilateral sciatica

Although cocaine induced myopathy and myotoxicity are described in the literature, we report a rare case of cocaine induced paraspinal myositis presenting with acute sciatic symptoms. A 35-year-old man presented with acute left-sided sciatica and was discharged from the emergency department (ED). He subsequently attended ED the following day in severe pain and bilateral sciatic symptoms, but denied symptoms of neurogenic bowel/bladder disturbance. Clinical examination was limited by severe pain: focal midline lumbar tenderness was elicited on palpation, per rectal and limb examinations were within normal limits with no significant neurological deficit. He was admitted for observation and pain management. His blood tests revealed a leucocyte count of 21.5x109/L, C reactive protein of 89 mg/L and deranged renal function with creatinine of 293 μmol/L. An urgent lumbar spine MRI was arranged to rule out a discitis or epidural abscess. Lumbar MRI did not demonstrate any features of discitis but non-specific appearances of paraspinal inflammation raised the suspicion of a paraspinal myositis. Creatinekinase (CK) was found to be 66329 IU/L and a detailed history revealed he was a cocaine user. Paraspinal muscle biopsy confirmed histological features compatible with myositis. Other serological tests were negative, including anti-GBM, ANCA, ANA, Rheumatoid factor, Hep B, Hep C, myositis specific ENA, Treponema pallidum, Borrelia burgdorferi, Rickettsia, Leptospira, EBV and CMV. There was good clinical response to treatment with prednisolone 20 mg OD with an improvement in renal function, CK levels and CRP. He had resumed normal activities and return to work at 6-week follow-up. A detailed social history including substance misuse is important in patients presenting to the ED—especially in cases of severe musculoskeletal pain with no obvious localising features. Drug induced myotoxicity, although rare, can result in symptomatic patients with severe renal failure.



https://ift.tt/2SfXip7

Retained tooth in the nasal cavity: a rare cause of nasal congestion

A 59-year-old man presented with unilateral nasal congestion and discharge. Clinical examination revealed a mass in the floor of the nasal cavity. Sinus CT indicated a retained tooth or a dermoid cyst. It was removed by endoscopic surgery. Histology confirmed the diagnosis of a retained tooth. At follow-up, the patient reported no nasal symptoms. A retained nasal tooth is rare, and the symptoms are variable. It can resemble other diseases such as chronic rhinosinusitis. Surgical removal is recommended to confirm the diagnosis and eliminate symptoms.



https://ift.tt/2XhuekX

Abdominal mass causing acute kidney injury as a manifestation of acute myeloid leukaemia



https://ift.tt/2SjblKP

'Acute-angled bevel sign to assess donor lenticule orientation in ultra-thin descemet stripping automated endothelial keratoplasty

A 6.5-year-old boy with congenital hereditary endothelial dystrophy underwent clear corneal ultra-thin descemet stripping automated endothelial keratoplasty (DSAEK). After graft insertion, it was difficult to assess graft orientation due to hazy cornea. Intraoperative optical coherence tomography (iOCT) showed a well-attached graft and the bevelled edge of donor lenticule made an acute angle with the overlying stroma. Postoperative anterior segment OCT confirmed the presence of acute-angled bevel sign. A wetlab experiment was performed with experimental corneoscleral tissues to confirm the findings. Donor lenticule was injected in the artificial chamber with stromal-side up as well as stromal side-down. 'Acute-angled bevel sign' was observed on iOCT in the experimental cases with stromal-side up. In inverse graft, the acute-angled bevel was not observed, instead the configuration was obtuse angled. Identifying the 'acute-angled bevel sign' on iOCT confirms correct graft orientation after unfolding and is extremely useful for hazy corneas and ultrathin DSAEK lenticules.



https://ift.tt/2Xh31yR

Ewings sarcoma in maxilla

Ewing sarcoma is a lesion of bone, described in small round cell neoplasm. This tumour resembles primitive neuroectodermal tumour both clinically and histologically. Major difference between these two is that the former arises in the bone and the later in soft tissue. It appears most frequently in males at the age range of of 5–25 years, 80% of which occurs within first two decades of life. Males are more commonly affected than females. Present paper reported with a case report of male patient with 24-year-old showing Ewing's sarcoma of right maxilla.



https://ift.tt/2XhwMzF

Retinal and choroidal circulation determined by optical coherence tomography angiography in patient with amyloidosis

A 43-year-old woman who was diagnosed with the cryopyrine-associated periodic syndrome (CAPS) with severe renal failure and heart failure due to amyloid accumulation was examined by swept source optical cohernce tomography (OCT) (SS-OCT; DRI-OCT, Topcon, Tokyo, Japan) and optical coherence tomography angiography (OCTA) (RTVue XR Avanti, Optovue, Fremont, CA). Her best-corrected visual acuity was 20/40 OD and 20/25 OS. A hyporeflective band of about 100 µm thickness was seen just inferior to the retinal pigment epithelium in the cross-sectional SS-OCT images, but the deeper choroidal structures were clearly visible. In the OCTA images, the density of the retinal capillaries in the superficial and deep capillary plexus slabs were reduced, and no signals of the choroidal capillary slab was detected after removing the projection artefacts. The accumulation of amyloid can cause a reduction of both the retinal and choroidal capillary circulations although the circulation in the larger vessels are preserved.



https://ift.tt/2SlryyU

Melanotan-induced priapism: a hard-earned tan

Melanocortin analogues, such as melanotan, are illegally used for artificial tanning. They have also been suggested as possible therapeutic agents in the treatment of erectile dysfunction. This case study presents a patient attending the accident and emergency department, in a tertiary urology centre, with acute priapism after abdominal subcutaneous injection of melanotan. The priapism was diagnosed as 'low-flow' and managed with cavernosal aspiration, irrigation and subsequent intracavernosal injection of phenylephrine. The patient avoided requiring surgical shunting but had not yet recovered erectile function at 4-week follow-up. Acute priapism is an unreported side effect of melanocortin analogue use and this case report presents a patient managed without surgical intervention. Future therapeutic application of these agents will need to take this potential life altering complication into consideration.



https://ift.tt/2XdBtKG

Clinical Infectious Diseases

The Association of Antibiotic Stewardship With Fluoroquinolone Prescribing in Michigan Hospitals: A Multi-hospital Cohort Study
Abstract
Background
Fluoroquinolones increase the risk of Clostridioides difficile infection and antibiotic resistance. Hospitals often use pre-prescription approval or prospective audit and feedback to target fluoroquinolone prescribing. Whether these strategies impact aggregate fluoroquinolone use is unknown.
Methods
This study is a 48-hospital, retrospective cohort of general-care, medical patients hospitalized with pneumonia or positive urine culture between December 2015–September 2017. Hospitals were surveyed on their use of pre-prescription approval and/or prospective audit and feedback to target fluoroquinolone prescribing during hospitalization (fluoroquinolone stewardship). After controlling for hospital clustering and patient factors, aggregate (inpatient and post-discharge) fluoroquinolone (ciprofloxacin, levofloxacin, moxifloxacin) exposure was compared between hospitals with and without fluoroquinolone stewardship.
Results
There were 11 748 patients (6820 pneumonia; 4928 positive urine culture) included at 48 hospitals. All hospitals responded to the survey: 29.2% (14/48) reported using pre-prescription approval and/or prospective audit and feedback to target fluoroquinolone prescribing. After adjustment, fluoroquinolone stewardship was associated with fewer patients receiving a fluoroquinolone (37.1% vs 48.2%; P = .01) and fewer fluoroquinolone treatment days per 1000 patients (2282 vs 3096 days/1000 patients; P = .01), driven by lower inpatient prescribing. However, most (66.6%) fluoroquinolone treatment days occurred after discharge, and hospitals with fluoroquinolone stewardship had twice as many new fluoroquinolone starts after discharge as hospitals without (15.6% vs 8.4%; P = .003).
Conclusions
Hospital-based stewardship interventions targeting fluoroquinolone prescribing were associated with less fluoroquinolone prescribing during hospitalization, but not at discharge. To limit aggregate fluoroquinolone exposure, stewardship programs should target both inpatient and discharge prescribing.


Prevalence, Predictors, and Successful Treatment Outcomes of Xpert MTB/RIF–identified Rifampicin-resistant Tuberculosis in Post-conflict Eastern Democratic Republic of the Congo, 2012–2017: A Retrospective Province-Wide Cohort Study
Abstract
Background
Multidrug-resistant tuberculosis (MDR-TB) jeopardizes global TB control. The prevalence and predictors of Rifampicin-resistant (RR) TB, a proxy for MDR-TB, and the treatment outcomes with standard and shortened regimens have not been assessed in post-conflict regions, such as the South Kivu province in the eastern Democratic Republic of the Congo (DRC). We aimed to fill this knowledge gap and to inform the DRC National TB Program.
Methods
of adults and children evaluated for pulmonary TB by sputum smear microscopy and Xpert MTB/RIF (Xpert) from February 2012 to June 2017. Multivariable logistic regression, Kaplan–Meier estimates, and multivariable Cox regression were used to assess independent predictors of RR-TB and treatment failure/death.
Results
Of 1535 patients Xpert-positive for TB, 11% had RR-TB. Independent predictors of RR-TB were a positive sputum smear (adjusted odds ratio [aOR] 2.42, 95% confidence interval [CI] 1.63–3.59), retreatment of TB (aOR 4.92, 95% CI 2.31–10.45), and one or more prior TB episodes (aOR 1.77 per episode, 95% CI 1.01–3.10). Over 45% of RR-TB patients had no prior TB history or treatment. The median time from Xpert diagnosis to RR-TB treatment initiation was 12 days (interquartile range 3–60.2). Cures were achieved in 30/36 (83%) and 84/114 (74%) of patients on 9- vs 20/24-month MDR-TB regimens, respectively (P = .06). Predictors of treatment failure/death were the absence of directly observed therapy (DOT; adjusted hazard ratio [aHR] 2.77, 95% CI 1.2–6.66) and any serious adverse drug event (aHR 4.28, 95% CI 1.88–9.71).
Conclusions
Favorable RR-TB cure rates are achievable in this post-conflict setting with a high RR-TB prevalence. An expanded Xpert scale-up; the prompt initiation of shorter, safer, highly effective MDR-TB regimens; and treatment adherence support are critically needed to optimize outcomes.


The Association of Antibiotic Stewardship With Fluoroquinolone Prescribing in Michigan Hospitals: A Multi-hospital Cohort Study
Abstract
Background
Fluoroquinolones increase the risk of Clostridioides difficile infection and antibiotic resistance. Hospitals often use pre-prescription approval or prospective audit and feedback to target fluoroquinolone prescribing. Whether these strategies impact aggregate fluoroquinolone use is unknown.
Methods
This study is a 48-hospital, retrospective cohort of general-care, medical patients hospitalized with pneumonia or positive urine culture between December 2015–September 2017. Hospitals were surveyed on their use of pre-prescription approval and/or prospective audit and feedback to target fluoroquinolone prescribing during hospitalization (fluoroquinolone stewardship). After controlling for hospital clustering and patient factors, aggregate (inpatient and post-discharge) fluoroquinolone (ciprofloxacin, levofloxacin, moxifloxacin) exposure was compared between hospitals with and without fluoroquinolone stewardship.
Results
There were 11 748 patients (6820 pneumonia; 4928 positive urine culture) included at 48 hospitals. All hospitals responded to the survey: 29.2% (14/48) reported using pre-prescription approval and/or prospective audit and feedback to target fluoroquinolone prescribing. After adjustment, fluoroquinolone stewardship was associated with fewer patients receiving a fluoroquinolone (37.1% vs 48.2%; P = .01) and fewer fluoroquinolone treatment days per 1000 patients (2282 vs 3096 days/1000 patients; P = .01), driven by lower inpatient prescribing. However, most (66.6%) fluoroquinolone treatment days occurred after discharge, and hospitals with fluoroquinolone stewardship had twice as many new fluoroquinolone starts after discharge as hospitals without (15.6% vs 8.4%; P = .003).
Conclusions
Hospital-based stewardship interventions targeting fluoroquinolone prescribing were associated with less fluoroquinolone prescribing during hospitalization, but not at discharge. To limit aggregate fluoroquinolone exposure, stewardship programs should target both inpatient and discharge prescribing.


Prevalence, Predictors, and Successful Treatment Outcomes of Xpert MTB/RIF–identified Rifampicin-resistant Tuberculosis in Post-conflict Eastern Democratic Republic of the Congo, 2012–2017: A Retrospective Province-Wide Cohort Study
Abstract
Background
Multidrug-resistant tuberculosis (MDR-TB) jeopardizes global TB control. The prevalence and predictors of Rifampicin-resistant (RR) TB, a proxy for MDR-TB, and the treatment outcomes with standard and shortened regimens have not been assessed in post-conflict regions, such as the South Kivu province in the eastern Democratic Republic of the Congo (DRC). We aimed to fill this knowledge gap and to inform the DRC National TB Program.
Methods
of adults and children evaluated for pulmonary TB by sputum smear microscopy and Xpert MTB/RIF (Xpert) from February 2012 to June 2017. Multivariable logistic regression, Kaplan–Meier estimates, and multivariable Cox regression were used to assess independent predictors of RR-TB and treatment failure/death.
Results
Of 1535 patients Xpert-positive for TB, 11% had RR-TB. Independent predictors of RR-TB were a positive sputum smear (adjusted odds ratio [aOR] 2.42, 95% confidence interval [CI] 1.63–3.59), retreatment of TB (aOR 4.92, 95% CI 2.31–10.45), and one or more prior TB episodes (aOR 1.77 per episode, 95% CI 1.01–3.10). Over 45% of RR-TB patients had no prior TB history or treatment. The median time from Xpert diagnosis to RR-TB treatment initiation was 12 days (interquartile range 3–60.2). Cures were achieved in 30/36 (83%) and 84/114 (74%) of patients on 9- vs 20/24-month MDR-TB regimens, respectively (P = .06). Predictors of treatment failure/death were the absence of directly observed therapy (DOT; adjusted hazard ratio [aHR] 2.77, 95% CI 1.2–6.66) and any serious adverse drug event (aHR 4.28, 95% CI 1.88–9.71).
Conclusions
Favorable RR-TB cure rates are achievable in this post-conflict setting with a high RR-TB prevalence. An expanded Xpert scale-up; the prompt initiation of shorter, safer, highly effective MDR-TB regimens; and treatment adherence support are critically needed to optimize outcomes.


Glycocalyx Breakdown is Associated with Severe Disease and Fatal Outcome in Plasmodium falciparum Malaria
Abstract
Background
Interactions between the endothelium and infected erythrocytes, microvascular dysfunction and parasite sequestration play major roles in the pathogenesis of severe falciparum malaria. The glycocalyx is a carbohydrate-rich layer lining the endothelium mediating NO production and vascular homeostasis. The role of the glycocalyx in falciparum malaria and the association with disease severity is not known.
Methods
We prospectively enrolled Indonesian inpatients (≥18 years old) with severe (SM) or moderately-severe (MSM) falciparum malaria and healthy controls (HCs). Glycocalyx breakdown products were measured in enrolment samples of urine (glycosaminoglycans; dimethylmethylene blue [GAG-DMMB] and liquid chromatography-tandem mass spectrometry [GAG-MS] assays) and plasma (syndecan-1; ELISA), and related to vascular NO bioavailability (reactive hyperemia-peripheral arterial tonometry).
Results
A total of 129 subjects (SM=43, MSM=57, HC=29) were recruited. Syndecan-1 (µg/ml), GAG-DMMB and GAG-MS (g/mol creatinine) were increased in SM [median (range) 332.4 (85-3-1913), 3.16 (0.04-27.9) and 4.73 (2.02-27.13)] compared to MSM [99.1 (19.9-767.6), 1.28 (0.03-9.3) and 4.44 (1.19-13.87)], and HCs [48.9 (32.3-88.3), 0.11 (0.02-1.9) and 2.55 (0.73-10.19)]; P<0.001. In SM, GAG-DMMB and GAG-MS were increased in non-survivors (n=3) [median (IQR): 6.72 (3.80-27.87) and 12.15 (7.88-17.20)] compared to survivors n=39 [(3.10 (0.46-4.5) and 4.64 (2.02-15.20)]; P=0.03. Glycocalyx degradation was associated with parasite biomass in MSM (r=0.31, P=0.03 [syndecan-1]; r=0.48 [GAG-DMMB] and r=0.43 [GAG-MS], P<0.001), and SM patients (r=0.29, P=0.04, r=0.47; P=0.002 and r=0.33, P=0.04), and inversely associated with endothelial NO bioavailability.
Conclusions
Increased endothelial glycocalyx breakdown is associated with impaired vascular NO, severe disease and fatal outcome in adults with falciparum malaria, likely contributing to pathogenesis.


Impact of rotavirus vaccine introduction in children less than 2 years of age presenting for medical care with diarrhea in rural Matlab, Bangladesh
Abstract
Background
Following the conclusion of a Rotarix vaccine (HRV) cluster-randomized controlled trial (CRT) in Matlab, Bangladesh, HRV was included in Matlab's routine immunization program. We describe the population-level impact of programmatic rotavirus vaccination in Bangladesh in children <2 years of age
Methods
Interrupted time series were used to estimate the impact of HRVintroduction. Diarrheal surveillance collected between 2000 and 2014 within the two service delivery areas (icddr,b service area [ISA] and government service area [GSA]) of the Matlab Health and Demographic Surveillance System administered by icddr,b was used. Age-group specific incidence rates were calculated for both rotavirus-positive (RV+) and rotavirus-negative (RV-) diarrhea of any severity presenting to the hospital. Two models were used to assess impact within each service area: Model 1 used the pre-vaccine time period in all villages (HRV- and control-only) and Model 2 combined the pre-vaccine time period and the CRT time period using outcomes from control-only villages.
Results
Both models demonstrated a downward trend in RV+ diarrheal incidence in the ISA villages during 3.5 years of routine HRV use, though only Model 2 was statistically significant. Significant impact of HRV on RV+ diarrhea incidence in GSA villages was not observed in either model. Differences in population-level impact between the two delivery areas may be due to varied rotavirus vaccine coverage and presentation rate to the hospital.
Conclusions
This study provides initial evidence of the population-level impact of rotavirus vaccines in children <2 years of age in Matlab, Bangladesh. Further studies of rotavirus vaccine impact after nationwide introduction in Bangladesh are needed.


Transmission-blocking effects of primaquine and methylene blue suggest P. falciparum gametocyte sterilisation rather than effects on sex ratio
Abstract
Gametocyte density and sex-ratio can predict the proportion of mosquitoes that become infected after feeding on blood of patients receiving non-gametocytocidal drugs. Because primaquine and methylene blue sterilize gametocytes before affecting their density and sex-ratio, mosquito feeding experiments are required to demonstrate their early transmission-blocking effects.


Principal Controversies in Vaccine Safety in the United States
Abstract
Concerns about vaccine safety can lead to decreased acceptance of vaccines and resurgence of vaccine-preventable diseases. We summarize the key evidence on some of the main current vaccine safety controversies in the United States, including: 1) MMR vaccine and autism; 2) thimerosal, a mercury-based vaccine preservative, and the risk of neurodevelopmental disorders; 3) vaccine-induced Guillain-Barré Syndrome (GBS); 4) vaccine-induced autoimmune diseases; 5) safety of HPV vaccine; 6) aluminum adjuvant-induced autoimmune diseases and other disorders; and 7) too many vaccines given early in life predisposing children to health and developmental problems. A possible small increased risk of GBS following influenza vaccination has been identified, but the magnitude of the increase is less than the risk of GBS following influenza infection. Otherwise, the biological and epidemiologic evidence does not support any of the reviewed vaccine safety concerns.


Insertion as resistance mechanism against integrase inhibitors in several retroviruses


Birth Cohort Studies Assessing Norovirus Infection and Immunity in Young Children: A Review
Abstract
Globally, noroviruses are among the foremost causes of acute diarrheal disease, yet there are many unanswered questions on norovirus immunity, particularly following natural infection in young children during the first 2 years of life when the disease burden is highest. We conducted a literature review on birth cohort studies assessing norovirus infections in children from birth to early childhood. Data on infection, immunity, and risk factors are summarized from 10 community-based birth cohort studies conducted in low- and middle-income countries. Up to 90% of children experienced atleast one norovirus infection and up to 70% experienced norovirus-associated diarrhea, most often affecting children 6 months of age and older. Data from these studies help to fill critical knowledge gaps for vaccine development, yet study design and methodological differences limit comparison between studies, particularly for immunity and risk factors for disease. Considerations for conducting future birth cohort studies on norovirus are discussed.


In the Literature


Saddle Nose Deformity in an Immunosuppressed Patient


Cover


News


Ebola's Curse: 2013–2016 Outbreak in West Africa
By OldstoneMichael and OldstoneMadeleine. Elsevier, 2017. 126 pp. $89.95 (hardcover). ISBN: 9780128138885.

Cost-effectiveness and Cost-utility of the Adherence Improving Self-management Strategy in Human Immunodeficiency Virus Care: A Trial-based Economic Evaluation
Abstract
Background
Several promising human immunodeficiency virus (HIV) treatment adherence interventions have been identified, but data about their cost-effectiveness are lacking. This study examines the trial-based cost-effectiveness and cost-utility of the proven-effective Adherence Improving Self-Management Strategy (AIMS), from a societal perspective, with a 15-month time horizon.
Methods
Treatment-naive and treatment-experienced patients at risk for viral rebound were randomized to treatment as usual (TAU) or AIMS in a multicenter randomized controlled trial in the Netherlands. AIMS is a nurse-led, 1-on-1 self-management intervention incorporating feedback from electronic medication monitors, delivered during routine clinical visits. Main outcomes were costs per reduction in log10 viral load, treatment failure (2 consecutive detectable viral loads), and quality-adjusted life-years (QALYs).
Results
Two hundred twenty-three patients were randomized. From a societal perspective, AIMS was slightly more expensive than TAU but also more effective, resulting in an incremental cost-effectiveness ratio (ICER) of €549 per reduction in log10 viral load and €1659 per percentage decrease in treatment failure. In terms of QALYs, AIMS resulted in higher costs but more QALYs compared to TAU, which resulted in an ICER of €27759 per QALY gained. From a healthcare perspective, AIMS dominated TAU. Additional sensitivity analyses addressing key limitations of the base case analyses also suggested that AIMS dominates TAU.
Conclusions
Base case analyses suggests that over a period of 15 months, AIMS may be costlier, but also more effective than TAU. All additional analyses suggest that AIMS is cheaper and more effective than TAU. This trial-based economic evaluation confirms and complements a model-based economic evaluation with a lifetime horizon showing that AIMS is cost-effective.
Clinical Trials Registration
NCT01429142


First Human Case of Metacestode Infection Caused by Versteria sp. in a Kidney Transplant Recipient
Abstract
Cestodes are emerging agents of severe opportunistic infections among immunocompromised patients. We describe the first case of human infection, with the recently-proposed genus Versteria causing an invasive, tumor-like hepatic infection with regional and distant extension in a 53-year-old female kidney transplant recipient from Atlantic Canada.


Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate is Non-inferior to Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate in Treatment-naive Adults With Human Immunodeficiency Virus–1 Infection: Week 48 Results of the DRIVE-AHEAD Trial
Abstract
Background
Doravirine (DOR), a novel non-nucleoside reverse-transcriptase inhibitor (NNRTI), is active against wild-type Human Immunodeficiency Virus (HIV)-1 and the most common NNRTI-resistant variants, and has a favorable and unique in vitro resistance profile.
Methods
DRIVE-AHEAD is a phase 3, double-blind, non-inferiority trial. Antiretroviral treatment–naive adults with ≥1000 HIV-1 RNA copies/mL were randomized (1:1) to once-daily, fixed-dose DOR at 100 mg, lamivudine at 300 mg, and tenofovir disoproxil fumarate (TDF) at 300 mg (DOR/3TC/TDF) or to efavirenz at 600 mg, emtricitabine at 200 mg, and TDF at 300 mg (EFV/FTC/TDF) for 96 weeks. The primary efficacy endpoint was the proportion of participants with <50 HIV-1 RNA copies/mL at week 48 (Food and Drug Administration snapshot approach; non-inferiority margin 10%).
Results
Of the 734 participants randomized, 728 were treated (364 per group) and included in the analyses. At week 48, 84.3% (307/364) of DOR/3TC/TDF recipients and 80.8% (294/364) of EFV/FTC/TDF recipients achieved <50 HIV-1 RNA copies/mL (difference 3.5%, 95% CI, -2.0, 9.0). DOR/3TC/TDF recipients had significantly lower rates of dizziness (8.8% vs 37.1%), sleep disorders/disturbances (12.1% vs 25.2%), and altered sensorium (4.4% vs 8.2%) than EFV/FTC/TDF recipients. Mean changes in fasting low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) (-3.83 vs +13.26 mg/dL) were significantly different between DOR/3TC/TDF and EFV/FTC/TDF (−1.6 vs +8.7 mg/dL and −3.8 vs +13.3 mg/dL, respectively).
Conclusions
In HIV-1 treatment-naive adults, DOR/3TC/TDF demonstrated non-inferior efficacy to EFV/FTC/TDF at week 48 and was well tolerated, with significantly fewer neuropsychiatric events and minimal changes in LDL-C and non–HDL-C compared with EFV/FTC/TDF.
Clinical Trials Registration
NCT02403674


A 44-Year-Old Female With Overwhelming Sepsis
sepsisaspleniaRPSA geneHowell-Jolly bodiesStreptococcus pneumonia

Concurrent Seroprevalence of Antibodies to Toxoplasma gondii and Toxocara Species in the United States, 2011–2014
To the Editor—We report supplemental findings incorporating Toxoplasma gondii serology results from our study of risk factors for Toxocara seropositivity in the United States [1] using stored serum samples collected from the National Health and Nutrition Examination Survey (NHANES), 2011–2014. Whereas T. gondii is a protozoan parasite and Toxocara is an intestinal nematode, both share ingestion of contaminated soil as means of exposure in humans. Both parasites can contaminate soil when environmentally resistant T. gondii oocysts or Toxocara cati eggs are shed in the feces of infected cats [23].





Hepatitis C Guidance 2018 Update: AASLD-IDSA Recommendations for Testing, Managing, and Treating Hepatitis C Virus Infection
Abstract
Recognizing the importance of timely guidance regarding the rapidly evolving field of hepatitis C management, the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) developed a web-based process for the expeditious formulation and dissemination of evidence-based recommendations. Launched in 2014, the hepatitis C virus (HCV) guidance website undergoes periodic updates as necessitated by availability of new therapeutic agents and/or research data. A major update was released electronically in September 2017, prompted primarily by approval of new direct-acting antiviral agents and expansion of the guidance's scope. This update summarizes the latest release of the HCV guidance and focuses on new or amended recommendations since the previous September 2015 print publication. The recommendations herein were developed by volunteer hepatology and infectious disease experts representing AASLD and IDSA and have been peer reviewed and approved by each society's governing board.


Functional Improvements Utilizing the Short Physical Performance Battery (SPPB) in the Elderly after Epidural Steroid Injections

Abstract

Purpose of Review

The treatment of debilitating pain and loss of function secondary to lumbar stenosis is in high demand with the aging patient population. Options, including epidural steroid injections (ESIs) and medication therapy, are limited and it is unclear if they provide any functional improvements. In this prospective study, we evaluate functional outcomes in older adults with symptomatic lumbar stenosis treated with ESIs compared to those managed with medications by introducing the Short Physical Performance Battery (SPPB). Our study was IRB-approved and included 16 patients, 68 to 83 years old, with symptomatic back and radicular leg pain secondary to lumbar stenosis. Patients could elect to undergo a lumbar ESI (n = 11) or be treated via medication management (n = 5). Numeric pain score, SPPB score, and adverse events were measured and compared at baseline and a 1-month follow-up visit.

Recent Findings

Statistically significant improvements were observed from baseline compared to the 1-month follow-up for total SPPB score in the injection group. Similar improvements in the injection group were observed for pain scores and the SPPB subcomponents such as the 4-m walk test, chair stand time, and balance score. Comparatively, no statistically significant improvements were observed in the medication group.

Summary

Lumbar ESIs improved objective physical capacity parameters and pain scores in elderly patients with symptomatic lumbar stenosis compared to medication management. In addition, the SPPB is an easy-to-use tool to measure changes in physical function in older adults and could easily be integrated into an outpatient pain clinic.



https://ift.tt/2BNUOsL

Perioperative Considerations in the Management of Anticoagulation Therapy for Patients Undergoing Surgery

Abstract

Purpose of Review

As ambulatory surgery has become increasingly more common, the appropriate management of anticoagulation therapy in patients undergoing invasive procedures has become progressively more relevant to healthcare professionals. The purpose of this literature review is to provide an overview of current common anaticoagulants and their pharmacological properties and to evaluate recent relevant literature and bridging therapy and provide recommendations on risk-guided therapy.

Recent Findings

With the development of new drugs and the advancing study and practice of anticoagulation use, clinicians must keep up-to-date on the optimal management of patients requiring anticoagulation. NOACs and warfarin continue to be the mainstays of treatment, with varying timelines regarding when to hold administration of the different agents within the perioperative period.

Summary

There are numerous factors that are considered in patients with multiple comorbidities including the risk for stroke on long-term anticoagulation and risk for thromboembolism, particularly in the perioperative setting when certain medication regimens may be altered and/or briefly held. There is ongoing investigation whether certain NOACs have more efficacy or greater safety profiles, depending on the degree of surgical intervention.



https://ift.tt/2U2w6Mq

Expression of Wnt‐1 and TSLC1 in condyloma acuminatum

Summary

Background

Despite its high contagiousness, high recurrence rate and potential for malignant transformation, effective treatments for condyloma acuminatum (CA) have not yet been developed. Accordingly, it is necessary to clarify the mechanisms underlying CA development.

Aim

To investigate the expression and significance of the proteins Wnt‐1 and TSLC1 in patients with CA and in normal foreskin controls.

Methods

Wnt‐1 and TSLC1 were assessed by immunohistochemistry in 45 patients with CA.

Results

Positive expression rates of Wnt‐1 and TSLC1 were 82.22% (37/45) and 37.78% (17/45), respectively, in CA tissues, and 29.17% (7/24) and 91.67% (22/24), respectively, in normal foreskin controls. Wnt‐1 expression intensity in CA was markedly higher (positive to strongly positive) than that in normal controls (negative to weakly positive), whereas TSLC1 expression intensity ranged from weakly positive to positive in CA, and nearly strongly positive in the normal control group. The differences in the positive expression rate and expression intensity of Wnt‐1 and TSLC1 between the two groups were statistically significant (< 0.05). In addition, Wnt‐1 and TSLC1 were negatively correlated. (r = −0.336, P < 0.05).

Conclusions

Overexpression of Wnt‐1 and low expression of TSLC1 may be associated with the growth of CA. These findings may provide a basis for the development of therapies to prevent recurrence or malignant transformation of CA.



https://ift.tt/2GEn2ug

Nail cosmetics: a dermatological perspective

Summary

Nail cosmetics are used by millions worldwide and the variety of products available is expanding. They are relatively safe, but complications can occur, and patients experiencing complications may present to dermatologists. The physical processes can cause nail thinning and onycholysis, poor technique can promote infection, and consumers may develop allergic contact dermatitis. Ultraviolet nail lamps are widely used for curing gel nails, but their use is unregulated and they are readily accessible in salons or for home use. There is concern about potential carcinogenesis; however, the risk is negligible and can be further reduced with the use of sunscreen. Despite the potential complications, nail cosmetics may be a useful adjunct in treating nail disorders. Familiarity with the procedures will enable the dermatologist to recognize problems and advise on safe use.



https://ift.tt/2NlzuiN

The efficacy of combined diluted calcium hydroxylapatite‐based filler and an energy‐based device in the treatment of facial atrophic acne scars

Abstract

Background and Objectives

Treatment options for atrophic acne scars include the use of various energy‐based devices (EBDs) and dermal fillers.

Aim

To evaluate the level of improvement and safety of four treatment modalities for atrophic acne scars employed in our center.

Methods

We reviewed the medical records of all acne scar patients treated between 2013‐2016 with one of four treatment modalities: ablative fractional CO2 laser (FACL), the radiofrequency (RF) bipolar device, the 1540 nm non‐ablative fractional laser (NAFL), and the injection of diluted calcium hydroxylapatite (CaHA). The EBDs were used as monotherapy or in combination with diluted CaHA. Two non‐involved dermatologists and the patients evaluated the aesthetic improvement achieved following the various modalities. The patients also rated their satisfaction, numbered the days of post‐treatment downtime, and reported any adverse effects.

Results

In total, 352 patients (mean age 28.7±8.7, 65.6% females) were treated for acne scars. The integrated mean dermatologists' and patients' GAS scores were the highest for the patients treated with the combined FACL‐CaHA modality at separate sessions (P < 0.001). Patients treated with FACL reported more side effects and longer downtime and duration of erythema.

Conclusions

The combination of a diluted CaHA‐based filler injection followed by fractional ablative CO2 laser in separate treatment sessions yielded better aesthetic improvement compared to the other tested modalities.

This article is protected by copyright. All rights reserved.



https://ift.tt/2GDtlxZ

Precision Medicine in Rhinosinusitis

Abstract

Purpose of Review

Our scope is the presentation of research and clinical progresses in relation to precision medicine that are expected to alter our clinical practice in relation to chronic rhinosinusitis (CRS). Current knowledge on phenotypes and endotypes, biomarkers, and clinical markers for diagnosis, medical and surgical therapy, and prognosis is presented as well as the role of precision medicine in United Airway Disease and SCUAD (severe-uncontrolled chronic upper airway inflammation).

Recent Findings

Current technological progresses, mostly in relation to molecular biology and information technology, have permitted more detailed pathophysiological assessments and multidimensional approaches in airways diseases. Based on the concept of united airways diseases, new classification schemes, called endotypes, have been proposed for CRS. In addition, novel biological treatments that have been introduced for the treatment of asthma show great promise as well for severe uncontrolled cases of CRS with nasal polyps. Central to this approach are new biomarkers that are being examined in relation to complex bio-clinical traits of CRS.

Summary

As this narrative review of the aforementioned precision medicine initiatives in relation to CRS advances, a modification of current practice is expected not only for severe chronic upper airways diseases in tertiary centers but also for milder and more common cases that are being encountered in the community.



https://ift.tt/2GWGIc3

Multimorbidities of Pediatric Allergic Rhinitis

Abstract

Purpose of Review

Most children and adolescents with allergic rhinitis (AR) present extra-nasal multimorbid conditions, including conjunctivitis, asthma, atopic dermatitis, rhinosinusitis, or seromucous otitis. Additionally, they may present nasal obstructive disorders, such as septal deformity, turbinate enlargement, and adenoidal hyperplasia, which worsen nasal symptoms, especially nasal obstruction. This is a narrative review on the current state of the concomitant presence of AR and one or more multimorbidities.

Recent Findings

The presence of AR and one or more accompanying multimorbidities is associated to a higher severity and duration of the disease, a negative impact on quality of life, with worse control and lack of improvement with medical treatment. Therefore, AR needs to be managed with a multidisciplinary collaborative approach.

Summary

Pediatric AR needs to be considered in the context of a systemic disease, which requires a coordinated therapeutic strategy.



https://ift.tt/2txq4rq

Pediatric Drug Hypersensitivity

Abstract

Purpose of Review

Pediatric drug hypersensitivity is a rapidly evolving field. The purpose of this paper is to review the current state of pediatric drug hypersensitivity and highlight new developments in diagnosis and management.

Recent Findings

This paper will discuss the safety and use of risk stratification to proceed directly to oral challenge without prior skin testing for β-lactam reactions. We review unique aspects of pediatric drug challenges and desensitizations.

Summary

It is important to accurately diagnose pediatric drug hypersensitivity reactions through a detailed history, physical examination, and available diagnostic testing. Understanding of the underlying mechanism leads to appropriate classification which is necessary to direct management. The decision to perform drug challenge, desensitization, or recommend avoidance of a medication can have a significant impact on a patient's treatment. Utilization of weight-based dose and infusion rate adjustments for current drug challenge and desensitization protocols optimize success.



https://ift.tt/2NlbgFF

Surgery is not the only determinant of an outcome in patients with hypopharyngeal carcinoma

Abstract

Background

The aim of this study was to evaluate the outcomes in patients treated for hypopharyngeal carcinoma in a single‐center and the importance of considering how patient factors influence outcomes.

Methods

A retrospective review was conducted on patients who were seen at the Prince of Wales Hospital from 1968 to 2015. Kaplan‐Meier and Cox regression analyses were performed for each patient and treatment factor to investigate outcomes of local control, cancer‐specific survival (CSS), and ultimate local control.

Results

Three hundred thirty patients were analyzed. Significant multivariate predictors for improved local control and CSS were fitness for surgery, cancer operability, surgery with adjuvant radiotherapy, no treatment interruptions (P < .05). Five‐year local control (84%), CSS (50%), and ultimate local control (84%) rates were significantly higher in patients treated surgically with adjuvant radiotherapy, compared to single modality treatment (P < .05).

Conclusion

Patient factors influence the outcomes experienced by patients with hypopharyngeal carcinoma.



https://ift.tt/2ty157i

Pediatric Drug Hypersensitivity

Abstract

Purpose of Review

Pediatric drug hypersensitivity is a rapidly evolving field. The purpose of this paper is to review the current state of pediatric drug hypersensitivity and highlight new developments in diagnosis and management.

Recent Findings

This paper will discuss the safety and use of risk stratification to proceed directly to oral challenge without prior skin testing for β-lactam reactions. We review unique aspects of pediatric drug challenges and desensitizations.

Summary

It is important to accurately diagnose pediatric drug hypersensitivity reactions through a detailed history, physical examination, and available diagnostic testing. Understanding of the underlying mechanism leads to appropriate classification which is necessary to direct management. The decision to perform drug challenge, desensitization, or recommend avoidance of a medication can have a significant impact on a patient's treatment. Utilization of weight-based dose and infusion rate adjustments for current drug challenge and desensitization protocols optimize success.



https://ift.tt/2NlbgFF

Dupilumab provides important clinical benefits to patients with atopic dermatitis who do not achieve clear or almost clear skin according to the Investigator's Global Assessment: a pooled analysis of data from 2 phase III trials

Summary

Background

In the US, an Investigator's Global Assessment (IGA) score of ≤ 1 (clear/almost clear skin) has been the regulatory outcome standard measure for registration clinical trials in atopic dermatitis (AD), including those supporting the recent approval of dupilumab.

Objective

To evaluate the treatment effect of dupilumab in patients with IGA>1 at the end of treatment, using other validated outcome measures for AD signs, symptoms and quality of life.

Methods

LIBERTY AD SOLO 1 and 2 were two 16‐week, randomized, double‐blind trials enrolling adult patients with moderate‐to‐severe AD (IGA≥3) inadequately controlled with topical treatment. We performed a post‐hoc analysis in patients receiving dupilumab 300 mg every 2 weeks (q2w) or placebo. Outcome measures in patients with IGA>1 included Eczema Area and Severity Index (EASI), pruritus Numerical Rating Scale (NRS), affected Body Surface Area (BSA), Patient‐Oriented Eczema Measure (POEM), and Dermatology Life Quality Index (DLQI).

Results

At Week 16, 278/449 dupilumab q2w‐treated patients (median age 36·0 years) and 396/443 placebo‐treated patients had IGA>1. Among patients with IGA>1 at Week 16, dupilumab significantly improved several outcome measures compared with placebo: EASI (–48·9% vs. –11·3%, P<0·001), pruritus NRS (–35·2% vs. –9·1%, P < 0·001), BSA affected (–23·1% vs. –4·5%, P<0·001), POEM score ≥ 4‐point improvement (57·4% vs. 21·0%, P<0·001), and DLQI score ≥ 4‐point improvement (59·3% vs. 24·4%, P<0·001).

Conclusions

In patients with IGA>1 at Week 16, dupilumab induced statistically significant benefits in multiple validated outcome measures versus placebo. The IGA≤1 endpoint significantly underestimates clinically relevant dupilumab treatment effects.

This article is protected by copyright. All rights reserved.



https://ift.tt/2Emc2z2

Living with vulval lichen sclerosus: a systematic review

Abstract

Lichen sclerosus (LS) is an under‐researched disorder, particularly from the perspective of individuals who have the condition. A recent James Lind Alliance Priority Setting Partnership identified uncertainties in many aspects of the condition, including its impact on quality of life which was ranked within the 'Top 10' future research priorities.1,2 We set out to systematically review the qualitative literature exploring the lived experience of vulval LS (for the full protocol see PROSPERO ID:CRD42018106947)

This article is protected by copyright. All rights reserved.



https://ift.tt/2VaHvK8

Chemoradiotherapy could improve overall survival of patients with stage IV cutaneous squamous cell carcinoma: analysis of 34 cases

Abstract

Cutaneous squamous cell carcinoma (cSCC) is the second most common non‐melanoma skin cancer, comprising approximately 20% of all skin malignancies1. The prognoses of patients with unresectable disease, such as locally advanced tumour or distant metastases, are known to be relatively poor due to lack of effective standardized systemic therapies2,3. When surgery is not feasible, non‐surgical approaches such as chemotherapy, radiation therapy (RT), and chemoradiotherapy (CRT; chemotherapy with radiation), are considered as alternative treatments2.

This article is protected by copyright. All rights reserved.



https://ift.tt/2T7jpmi

Serum cytokeratin 19 fragment 21‐1 and carcinoembryonic antigen combination assay as a biomarker of tumour progression and treatment response in extramammary Paget's disease

Summary

Background

Extramammary Paget's disease (EMPD) is a rare intraepithelial adenocarcinoma affecting the genitals and axillary regions. As metastasis of these tumours is itself rare, solid disease management strategies have not been established. Serum carcinoembryonic antigen (CEA) and cytokeratin 19 fragment 21‐1 (CYFRA 21‐1) levels have been identified as candidate biomarkers for tumour progression in EMPD; however, neither the accuracy of, nor correlation between, these markers have been examined in EMPD patients.

Methods

Serum CEA and CYFRA 21‐1 levels were examined in 30 EMPD patients treated at Keio University Hospital, and compared against clinical information retrospectively. Both assays were performed at the time of diagnosis, during the postoperative observation period, and following systemic treatment in those with confirmed metastasis. Serum levels were then correlated with tumour progression status and treatment responses.

Results

Normal levels for both assays were observed in all 11 primary localised patients (100%). In metastatic patients, the CEA positivity rate was 78·9% (15/19 patients) and 63·1% (11/19 patients) for CYFRA 21‐1. Changes in CEA and CYFRA 21‐1 levels were statistically independent; however, using a combined view, elevated levels of either marker improved the positivity rate to 94·8% (18/19 patients). Use of both markers also correlated well with the treatment responses.

Conclusions

The combination of CEA and CYFRA 21‐1 is useful for predicting metastasis and treatment response in EMPD patients, especially in those who only have elevation of a single marker.

This article is protected by copyright. All rights reserved.



https://ift.tt/2IsWei0

Spindle cell liposarcoma with a TRIO-TERT fusion transcript

Abstract

Conventional well-differentiated, dedifferentiated, and myxoid liposarcomas have long been known to harbor numerous typical genetic alterations that allow for diagnosis of these tumors. These include MDM2 and CDK4 amplification in well-differentiated and dedifferentiated liposarcomas as well as FUS-DDIT3 rearrangements in myxoid liposarcoma. More recently, in-frame TRIO-TERT fusion genes have been described in a subset of non-translocation-related sarcomas including myxofibrosarcoma, dedifferentiated liposarcoma, undifferentiated pleomorphic sarcoma, pleomorphic rhabdomyosarcoma, and leiomyosarcoma. These genetic rearrangements lead to TERT mRNA expression levels hundreds of times higher than normal, causing increased telomerase activation in these tumors. Herein, we describe an unusual case of a liposarcoma with spindle cell features and a TRIO-TERT fusion transcript identified through next-generation sequencing.



https://ift.tt/2V70m8Q

Whatever Happened to Local Otolaryngology Societies?

This essay describes the importance of, and decline of membership in, specialty medical societies.

https://ift.tt/2PoHvmH

An Indolent Middle Ear Mass

A woman in her 30s with a 1-year history of left ear fullness presented with left-sided hearing that improved temporarily with autoinsufflation. What is your diagnosis?

https://ift.tt/2KHySD0

February Issue Highlights



https://ift.tt/2X9MVH8

Publication Bias and Systematic Reviews in Top-Ranked Otolaryngology Journals

This study analyzes whether 324 systematic reviews that contain at least 1 meta-analysis with 10 or more primary studies published in top otolaryngology journals that do not evaluate for publication bias show evidence of such bias.

https://ift.tt/2PmNh8o

Error in Figure Labels

In the article titled "Is It Time to Rethink the Approach to Internal Nasal Valve Stenosis?," the 2 Figure labels (a and b) were transposed so that the labels corresponded to the incorrect descriptions in the Figure caption. The Figure has been corrected online.

https://ift.tt/2Xq6Fqi

Association of Treatment Delays With Survival for Patients With Head and Neck Cancer

This systematic review synthesizes information about the association between delays in the delivery of care for head and neck cancer and oncologic outcomes.

https://ift.tt/2yKZ8Yq

Labels Reversed in Figure 1

In the Original Investigation titled "Association of Adjuvant Radiation Therapy With Survival in Patients With Advanced Cutaneous Squamous Cell Carcinoma of the Head and Neck" by Harris et al, the labels in Figure 1 were reversed. This article has been corrected online.

https://ift.tt/2Xgs19y

Pretreatment Hearing Level—Another Prognostic Factor in Sudden Sensorineural Hearing Loss—Reply

In Reply We thank Dr Wu and colleagues for their interest and comments on our research. Various factors may affect hearing recovery after SSHL, such as age, degree of hearing loss, type of hearing loss, interval from onset of symptoms to treatment, tinnitus, type 2 diabetes, cardiovascular disease, and the presence of vertigo. We were unable to include the hearing level at onset into our analyses owing to the lack of corresponding data in the included studies. Moreover, only 1 of the included studies assessed the possible association between the presence of vertigo and hearing recovery in patients with severe sudden sensorineural hearing loss (≥60 dB). We also think that the opinion by Dr Wu et al that the presence of vertigo is significantly correlated only with hearing recovery in the group with profound SSHL may have implications for the understanding of the mechanisms of SSHL with vertigo, but we were unable to retrieve the raw data. At present, the pathogenesis, clinical manifestations, optimal treatments, and prognostic factors of SSHL are not clear. We are in the process of validating the occurrence of vertigo and its possible role in SSHL. A complete analysis of this role will require more unbiased studies with prospectively gathered data in a large sample size to estimate the precise association of vertigo with the clinical manifestation and prognosis of SSHL.

https://ift.tt/2zNmYTN

Traumatic Lower Lip Myiasis

This is the report of a case of a homeless man in his 50s who presented with traumatic lower lip myiasis.

https://ift.tt/2Xhbzpx

Anemia and 30-Day Morbidity and Mortality After Thyroidectomy in Thyroid Cancer Treatment

This cross-sectional cohort study uses the American College of Surgeons National Surgical Quality Improvement Program database to evaluate whether an association exists between preoperative anemia and postoperative 30-day morbidity and mortality outcomes following thyroidectomy in adult patients with thyroid cancer.

https://ift.tt/2BHhDyL

Aspiration in Infants With Laryngomalacia and Respiratory and Feeding Difficulties

This study evaluates the medical records of infants with laryngomalacia and associated breathing and feeding difficulties to determine the prevalence of aspiration among this pediatric patient population.

https://ift.tt/2Xk66ho

Secondary Endolymphatic Hydrops Associated With Spontaneous Intracranial Hypotension

This case report describes a woman in her 40s who presented with spontaneous intracranial hypotension associated with cerebrospinal fluid leakage.

https://ift.tt/2zfO6dV

Silent Aspiration in Laryngomalacia?

Laryngomalacia is the most common laryngeal anomaly in infants, with a presentation of inspiratory stridor being nearly ubiquitous. In addition, young children with laryngomalacia can demonstrate feeding difficulty, dysphagia, aspiration, failure to thrive, apnea, cyanosis, and/or obstructive sleep apnea. Managing the balancing act between sucking, breathing, and swallowing is anticipated to carry additional challenge in infants with airway abnormalities, potentially leading to dysphagia, aspiration, and feeding difficulties. Somewhat unsurprisingly, infants with laryngomalacia may cough and choke during feeding, take their feeds slowly, or develop a worsening of their stridor during feeding. The association between laryngomalacia and feeding disorders is further strengthened by a biological gradient relationship, with more severe laryngomalacia cases shown to be more likely to have symptoms of feeding difficulty. In addition to dyscoordination, other proposed causes for feeding challenges in patients with laryngomalacia include decreased laryngeal sensation secondary to acid reflux and an alteration in the sensorimotor integrative function of the larynx. The association between acid reflux and laryngomalacia is well established, although evidence is lacking for causality or even direction of causality (ie, which is the chicken and which is the egg). Sensorimotor impairment in laryngomalacia is evidenced by the finding that children with laryngomalacia have higher rates of neurologic abnormalities such as hypotonia, central apneas and developmental disorders, and histopathologic nerve differences in their laryngeal mucosa.

https://ift.tt/2XgrSD2

JAMA Otolaryngology–Head & Neck Surgery

Mission Statement:JAMA Otolaryngology–Head & Neck Surgery provides timely information for physicians and scientists concerned with diseases of the head and neck. Given the diversity of structure and function based in this anatomic region, JAMA Otolaryngology–Head & Neck Surgery publishes clinical, translational, and population health research from an array of disciplines. We place a high priority on strong study designs that accurately identify etiologies, evaluate diagnostic strategies, and distinguish among treatment options and outcomes. Our objectives are to (1) publish original contributions that will enhance the clinician's understanding of otolaryngologic disorders, benefit the care of our patients, and stimulate research in our field; (2) forecast important advances within otolaryngology—head and neck surgery, particularly as they relate to the prevention, diagnosis, and treatment of disease through clinical and translational research, including that of the human genome and novel imaging techniques; (3) address questions of clinical outcomes and cost-effectiveness that result from clinical intervention, which grow in importance as health care providers are increasingly challenged to provide evidence of enhanced survival and quality of life; (4) provide expert reviews of topics that keep our readers current with true advances and also to provide a valuable educational resource for trainees in the several disciplines that treat patients with diseases of the head and neck; (5) serve as a forum for the concerns of otolaryngologists such as socioeconomic, legal, ethical, and medical issues; (6) provide helpful critiques that enable contributing authors to improve their submissions. We encourage a concise presentation of information and employ an abstract format that efficiently assesses validity and relevance from a clinical perspective. This approach promotes succinct yet complete presentation for our readers and electronic information resources. We believe this approach typifies the commitment of JAMA Otolaryngology–Head & Neck Surgery to providing important information that is easily interpreted by its diverse readership.

https://ift.tt/2ShQFTi

Drug-Induced Sleep Endoscopy Findings in Supine vs Nonsupine Body Positions in Obstructive Sleep Apnea

This cross-sectional study examines drug-induced sleep endoscopy findings in the supine vs nonsupine body positions in positional and nonpositional obstructive sleep apnea using VOTE classification criteria.

https://ift.tt/2PUTJUt

Association of Audiometric Age-Related Hearing Loss With Depressive Symptoms in Hispanic Individuals

This multicenter, cross-sectional study uses Community Health Study/Study of Latinos data collected from 4 US communities to assess whether an association exists between age-related, audiometrically measured hearing loss and clinically relevant depressive symptoms in Hispanic adults 50 years or older.

https://ift.tt/2zOweqJ

Adjuvant Radiation Therapy in Patients With Advanced CSCC of the Head and Neck

This study examines the association of adjuvant radiation therapy vs surgery alone with survival in patients with advanced cutaneous squamous cell carcinoma and assesses which patients benefit the most from addition of adjuvant therapy to surgical treatment.

https://ift.tt/2UXy6X6

Pretreatment Hearing Level—Another Prognostic Factor in Sudden Sensorineural Hearing Loss

To the Editor We read with great interest the article titled "Association of Vertigo With Hearing Outcomes in Patients With Sudden Sensorineural Hearing Loss: A Systematic Review and Meta-analysis" by Yu et al. The authors concluded that vertigo may be negatively associated with hearing recovery in patients with sudden sensorineural hearing loss (SSHL).

https://ift.tt/2PoLJdO

Variation in the Quality of US Head and Neck Cancer Care

This evaluation of quality metrics uses data from the National Cancer Database to summarize hospital-level overall quality of care for patients with head and neck cancer in the United States.

https://ift.tt/2UXy3KU

Anterior Nasal Cavity Mass in a Neonate

A newborn twin girl was evaluated for a left-sided nasal mass causing nasal obstruction and difficulty breathing; physical examination showed a firm, pedunculated polypoid mass in the anterior nasal cavity at the vestibule with no fluid in the mass. What is your diagnosis?

https://ift.tt/2zJiyNS

Clinical management for T1 and T2 external auditory canal cancer

The purpose of this study was to clarify the impact of superficial parotidectomy and postoperative radiotherapy (PORT) for the surgical treatment of early stage squamous cell carcinoma (SCC) in external auditory canal (EAC).

https://ift.tt/2TWw6NU

Oral administration of an herbal medicine to prevent progressive hearing loss in a mouse model of diabetes

Tsumura Suzuki Obese Diabetes (TSOD) mice exhibit early age-associated hearing loss. Histopathological analysis of these mice shows narrowing of capillaries in the stria vascularis and chronic reduction of blood flow in the cochlea. In this study, we investigated the effect of oral administration of a herbal medicine or calorie restriction on hearing in TSOD mice.

https://ift.tt/2BMva7M

Mobile Teledermatology for Melanoma Detection. Assessment of Validity in the Framework of a Population-based Skin Cancer Awareness Campaign in Northern Italy



https://ift.tt/2E0XnIl

Visual perception, cognition and error in dermatologic diagnosis, Part 2 of 2

Diagnostic error in dermatology is a large practice gap that has received little attention. Diagnosis in dermatology relies heavily on a heuristic approach responsible for our perception of clinical findings. In order to improve our diagnostic accuracy, a better understanding of the strengths and limitations of heuristics (cognitive short cuts) used in dermatology is essential. Numerous methods have been proposed to improve diagnostic accuracy, including brain training, reducing cognitive load, getting feedback and second opinions.

https://ift.tt/2GUG8LT

Cutaneous presentations of omphalomesenteric duct remnant: a systematic review of the literature

Disorders of the umbilicus are commonly seen in infancy including: hernias, infections, anomalies, granulomas and malignancies. Meticulous inspection of the umbilicus at birth may reveal a persisting embryonic remnant such as omphalomesenteric duct (OMD), manifested by a variety of cutaneous signs such as: an umbilical mass, granulation tissue or discharge.

https://ift.tt/2GUGceB

Characterization of chronic urticaria and associated conditions in a large population of adolescents

Although chronic spontaneous urticaria (CSU) affects all age groups, data regarding CSU in adolescents is scarce.

https://ift.tt/2SPQZxG

CME article part 1: Visual perception, cognition and error in dermatologic diagnosis

Dermatologic diagnosis relies on vision primarily and auditory and verbal input secondarily. Accurate dermatologic diagnosis is predicated on 1) seeing and perceiving a skin finding, 2) categorizing and naming the finding correctly, and 3) comparing the visual data and data obtained from the totality of the clinical encounter (i.e., from other sensory modalities) with one's working mental database of dermatologic diagnoses. The baseline assumption – which is false - is that a dermatologist is expert at each of the aforementioned steps and transitions sequentially between them seamlessly in an error-free fashion.

https://ift.tt/2twPd5F

Prison malpractice litigation involving dermatologists: A cross-sectional analysis of dermatologic medical malpractice cases involving incarcerated patients from 1970-2018



https://ift.tt/2twP9mr

Use of 5-0 Fast Absorbing Gut vs 6-0 Fast Absorbing Gut During Cutaneous Wound Closure on the Head and Neck: A Randomized Evaluator-Blinded Split-Wound Comparative Effectiveness Trial

Absorbable suture material (Fast Absorbing Gut (FG)) is often employed for patient convenience, however, the optimal diameter of FG sutures is debatable.

https://ift.tt/2GWn93B

Inflammatory dietary pattern and incident psoriasis, psoriatic arthritis, and atopic dermatitis in women: a cohort study

Diet is a modulator of inflammation and may impact inflammatory skin diseases.

https://ift.tt/2GBrycR

Radiation-induced morphea: association with autoimmune comorbidities, severity, and response to therapy



https://ift.tt/2tBHV0h

Laboratory Monitoring Requirements During Mycophenolate Mofetil Therapy for Dermatologic Conditions: A Single Institution Retrospective Chart Review



https://ift.tt/2GUG1Qt

The use of forceps for creating sustained pressure for slit skin smear



https://ift.tt/2tA6DOA

“More efficacious extraction of the molluscum body by supplanting needle with an angled forceps ”



https://ift.tt/2GUFZIl

A technique to cleanse follicular grafts



https://ift.tt/2twP1Dt

Understanding Error Rates in Software Engineering: Conceptual, Empirical, and Experimental Approaches

Abstract

Software-intensive systems are ubiquitous in the industrialized world. The reliability of software has implications for how we understand scientific knowledge produced using software-intensive systems and for our understanding of the ethical and political status of technology. The reliability of a software system is largely determined by the distribution of errors and by the consequences of those errors in the usage of that system. We select a taxonomy of software error types from the literature on empirically observed software errors and compare that taxonomy to Giuseppe Primiero's Minds and Machines 24: 249–273, (2014) taxonomy of error in information systems. Because Primiero's taxonomy is articulated in terms of a coherent, explicit model of computation and is more fine-grained than the empirical taxonomy we select, we might expect Primiero's taxonomy to provide insights into how to reduce the frequency of software error better than the empirical taxonomy. Whether using one software error taxonomy can help to reduce the frequency of software errors better than another taxonomy is ultimately an empirical question.



https://ift.tt/2IpkgdQ

Kopf-Hals-Tumoren erfordern ein individuelles und interdisziplinäres Behandlungskonzept



https://ift.tt/2XiuXCf

Lacrimal Duct Obstruction in a Teenager

A teenaged girl with chronic sinusitis and a history of osseous lesions in the upper and lower jaws presented with epiphora, purulent drainage, and jaw pain. What is your diagnosis?

https://ift.tt/2BMjKRz

Vertebral Bodies, Anterior Erosion, and Compression by Tracheostomy Canula

This case report describes a man in his late teens with scoliosis, muscular dystrophy, and severe osteoporosis who presented with a 3-month history of tracheal discomfort and light bleeding during tracheal aspiration.

https://ift.tt/2BOBFHk

Evaluation of a Preoperative Risk Index for Patients Undergoing Head and Neck Cancer Surgery

This cohort study evaluates a preoperative adverse event risk index in patients from the ACS NSQIP database who underwent surgery for head and neck cancer between 2006 and 2016.

https://ift.tt/2U0RtOe

Comparison of the Financial Burden of Survivors of Head and Neck Cancer With Other Cancer Survivors

This analysis of US nationally representative survey data assessed the financial burdens of patients with head and neck cancer compared with patients with other types of cancer.

https://ift.tt/2U0RotU

Eosinophilic Esophagitis—A Primer for Otolaryngologists

This narrative review discusses common presenting symptoms, associated otorhinolaryngology symptoms, diagnostic workup, endoscopic features, and treatment of eosinophilic esophagitis for the general otolaryngologist.

https://ift.tt/2BGtixp

Head and Neck Cancer Compared With Other Cancers—Does the Great Equalizer Equalize Equally?

When Andrew Lo, PhD, of the Massachusetts Institute of Technology Sloan School of Management stated, "Cancer is the great equalizer. Everyone is affected by it either themselves or through loved ones," we might infer that the experience of this very human tragedy would cut through factors that can be divisive, such as race, sex, educational status, and socioeconomic status. The implication is that before cancer we are all equal, regardless of such factors. However, the recent work by Massa et al indicates that this may not be the case.

https://ift.tt/2U0RlOK

The International Society of Urological Pathology Education web—a web-based system for training and testing of pathologists

Abstract

Pathology training resources remain scarce in many parts of the world. With rapid economic development comes the need to educate new pathologists to meet the medical care demands. Our aim was to set up a cost-effective system for training and testing the diagnostic skills of pathologists. Pathologists in nine countries in Asia and South America were invited by the International Society of Urological Pathology (ISUP) to participate in a prostate pathology education course combining image-based tests with lectures and on-line tutorials. The tests and tutorials are available free of charge at the ISUP education website www.edu.isupweb.org. A total of 603 pathologists registered on the website. Of these, 224 completed pre- and post-lecture assessments (tests 1 and 2). Replies were classified as correct/acceptable, when a lesion was accurately classified into clinically relevant categories (benign, cancer, high-grade prostatic intraepithelial neoplasia, intraductal carcinoma of the prostate). The rate of correct/acceptable replies increased from 60.7 to 72.3% in Tests 1 and 2, respectively. In Test 1, pathologists from upper middle, lower middle, and low resource countries gave a correct/acceptable diagnosis in 65.8%, 61.0%, and 47.4%, respectively. Their results improved in Test 2 to 76.4%, 72.5%, and 62.8%, respectively. The greatest improvement in diagnostic ability was achieved in pathologists from the low resource group of countries. The use of web-based testing and training, combined with lectures, is an efficient method for improving diagnostic skills of pathologists in low to middle resource countries.



https://ift.tt/2BK68q0

A Study of XmAb®22841 Monotherapy & in Combination w/ Pembrolizumab in Subjects w/ Selected Advanced Solid Tumors

Conditions:   Melanoma;   Cervical Carcinoma;   Pancreatic Carcinoma;   Triple Negative Breast Cancer;   Hepatocellular Carcinoma;   Urothelial Carcinoma;   Squamous Cell Carcinoma of the Head and Neck;   Nasopharyngeal Carcinoma;   Renal Cell Carcinoma;   Colorectal Carcinoma;   Endometrial Carcinoma;   Non-small Cell Lung Carcinoma;   Small Cell Lung Carcinoma;   Gastric or Gastroesophageal Junction Adenocarcinoma;   Advanced or Metastatic Solid Tumors
Interventions:   Biological: XmAb®22841;   Biological: Pembrolizumab (Keytruda®)
Sponsors:   Xencor, Inc.;   ICON plc
Not yet recruiting

https://ift.tt/2tyouFQ

Multiparametric Magnetic Resonance Imaging Versus Fine Needle Aspiration Cytology for Parotid Gland Neoplasms

Conditions:   Parotid Neoplasm;   Parotid Cancer
Interventions:   Diagnostic Test: Multiparametric Magnetic Resonance Imaging;   Diagnostic Test: Fine Needle Aspiration Cytology;   Diagnostic Test: Clinical Evaluation;   Diagnostic Test: Final Histopathological Diagnosis
Sponsor:   Davide Di Santo
Recruiting

https://ift.tt/2H1OIbV

Good Chore Ideas Your Child Can Handle

As a parent, we've probably all had trouble coming up with good chore ideas that are helpful and fun, instead of a struggle. It can often be very difficult to get our children to do chores without whining. But it's not impossible! In this video, Dr. Katherine Rivera shares some tips about age-appropriate chores for children. Watch to learn how you can turn chore time into family time.

The post Good Chore Ideas Your Child Can Handle appeared first on ChildrensMD.



https://ift.tt/2DYsC6O

Benefits of 1-Year Lifestyle Modification Program on Exercise Capacity and Diastolic Function Among Coronary Artery Disease Men With and Without Type 2 Diabetes

Metabolic Syndrome and Related Disorders, Ahead of Print.


https://ift.tt/2GCgnAK

Pneumocephalus and pneumoventricle

CASE REPORT
Year : 2019  |  Volume : 14  |  Issue : 1  |  Page : 325-328

Delayed pneumoventricle following endonasal cerebrospinal fluid rhinorrhea repair with thecoperitoneal shunt


Department of Neurosurgery, Achanta Lakshmipathi Neurosurgical Centre, Voluntary Health Services Hospital, Chennai, Tamil Nadu, India

Date of Web Publication21-Feb-2019

    

Correspondence Address:
Dr. Shyam Sundar Krishnan
Department of Neurosurgery, Achantha Lakshmipathy Neurosurgical Centre, Voluntary Health Services, TTTI Post, Taramani, Chennai - 600 113, Tamil Nadu 
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ajns.AJNS_224_18

Rights and Permissions
  Abstract 


Pneumocephalus and pneumoventricle are well-documented in neurosurgical practice. Although both are common posttraumatic sequelae, iatrogenic causes are also well recognized. Iatrogenic causes may be seen after intracranial surgical procedures or cerebrospinal fluid (CSF) diversion procedures. Small amount of pneumoventricle postshunt procedure is usually a self-limiting condition. Rarely, the patient may develop tension pneumoventricle which requires emergency intervention. The occurrence of delayed tension pneumoventricle/pneumatocele following surgery for CSF rhinorrhea with CSF diversion procedures is very rare. We report one case of late presentation of delayed tension pneumoventricle with temporal pneumatocele in a patient who underwent transnasal endoscopic repair of CSF fistula followed by thecoperitoneal shunt. This condition is potentially lethal that requires prompt recognition and surgical treatment.

Keywords: Cerebrospinal fluid rhinorrhea, pneumatocele, pneumocephalus, tension pneumoventricle, thecoperitoneal shunt


How to cite this article:
Krishnan SS, Manuel A, Vasudevan MC. Delayed pneumoventricle following endonasal cerebrospinal fluid rhinorrhea repair with thecoperitoneal shunt. Asian J Neurosurg 2019;14:325-8

How to cite this URL:
Krishnan SS, Manuel A, Vasudevan MC. Delayed pneumoventricle following endonasal cerebrospinal fluid rhinorrhea repair with thecoperitoneal shunt. Asian J Neurosurg [serial online] 2019 [cited 2019 Feb 21];14:325-8. Available from: http://www.asianjns.org/text.asp?2019/14/1/325/250010




  Introduction Top


The occurrence of pneumoventricle as a delayed complication of cerebrospinal fluid (CSF), rhinorrhea repair with thecoperitoneal shunt is a rare presentation. Tension pneumocephalus is a known and common entity as compared to tension pneumoventricle. The presence of pneumatocele in the temporal lobe in association with the above condition makes it a unique clinical presentation.


  Case Report Top


This 48-year-old female presented with complaints of CSF rhinorrhea since 2 months. There was no history or clinical finding suggestive of trauma or meningitis. Her neurological examination otherwise was unremarkable. Computed tomography (CT) face/skull base followed by magnetic resonance imaging (MRI) brain and diagnostic nasal endoscopy were done which showed the defect in the cribriform plate and left a lateral wall of the sphenoid sinus [Figure 1]. Lumbar puncture done showed the CSF opening pressure of 35 cm of water and no evidence of infection.
Figure 1: Magnetic resonance images of the patient showing cerebrospinal fluid fistula in cribriform plate (short arrow) and lateral wall of sphenoid sinus (long arrow) and computed tomography paranasal sinuses bone window showing defect (long arrow) in the sphenoid bone with cerebrospinal fluid filling into the left sphenoid sinus (long arrow)

Click here to view


She underwent transnasal endoscopic repair of CSF fistula along with placement of thecoperitoneal shunt with no anti-siphon device. The bath-plug technique was used to seal the defects by introducing a fat plug with a specifically secured vicryl suture into the intradural space, followed by applying traction on the suture to seal the defect much like a bathplug seals a bath. Rectus abdominis fascia graft was harvested from the same abdominal wound used for shunt placement. The defect was further reinforced by fascia, fat and surgical, and fibrin sealant. It was decided to place thecoperitoneal shunt as the CSF opening pressure was very high to prevent the recurrent CSF leak. Postoperatively, she was symptom-free and discharged to home.

After 1 month, she presented with memory disturbances, multiple episodes of vomiting and headache. There was no recurrence of CSF rhinorrhea or postnasal drip. MRI brain showed pneumoventricle with right temporal pneumatocele [Figure 2]. Diagnostic endoscopy was done which showed dislodged fascia graft. She underwent emergency repacking of the CSF fistula with the removal of thecoperitoneal shunt and aspiration of pneumoventricle underwater seal which was under high pressure. Fasica graft was repositioned to cover the defect after sealing it with fat using the bath-plug technique as in the previous surgery. Fat and fascia packing was reinforced with a pedicled Hadad flap and fibrin sealant. She improved in her symptoms postoperatively. Postoperative CT brain showed good resolution of pneumoventricle with reduced size of ventricular system [Figure 3]. She remained symptom free at 6-month follow-up.
Figure 2: Magnetic resonance imaging brain showing pneumatocele (long arrow) in the right temporal lobe and pneumoventricle (short arrow)

Click here to view
Figure 3: Postoperative computed tomography brain showing good resolution of tension pneumoventricle and right temporal pneumatocele

Click here to view



  Discussion Top


Pneumocephalus is defined as the presence of air in the intracranial compartment due to communication between intracranial and extracranial compartments.[1],[2],[3] Tension pneumocephalus is a rarer form of pneumocephalus in which the air is under high pressure.[1],[2],[4],[5],[6],[7]Pneumocephalus occur most commonly in head injuries.[1],[2],[3] Intra- and post-operative pneumocephalus/pneumoventricle is well-documented, especially, in sitting position surgeries, nitrous oxide anesthesia, and CSF diversion surgeries.[1],[2],[3] Other conditions causing pneumocephalus are CNS infections caused by gas-producing organisms, congenital neurenteric cysts, and postradiotherapy for nasopharyngeal carcinoma.[1],[2],[4],[5],[6],[7] Small amounts of pneumoventricle alone are common after shunt surgeries, ventricular tumor surgeries.[1],[2],[3],[8] Sometimes, wound breakdown following the shunt surgeries may cause influx of air peritubally and cause pneumoventricle.[9] Delayed tension pneumoventricle is an extremely rare complication and <50 cases have been described in the literature.[1]Pneumocephalus/pneumoventricle is usually benign which does not require any treatment, and it decreases at a rate of 25% per week.[4],[9],[10],[11],[12]

Two different mechanisms have been proposed in the development of delayed tension pneumoventricle/pneumocephalus.[1],[2],[3],[13],[14]

  1. Dandy's theory of ball valve mechanism: one-way ball valve mechanism causing air to flow into the skull through dural defect where the exit is prevented by brain or meninges sealing the leak site
  2. Horowitz inverted soda-bottle effect: negative pressure develops inside the cranial cavity as a result of excessive loss of CSF. This drop in intracranial pressure (ICP) causes air to flow from the extra to the intracranial space across the pressure gradient.


In our case, the patient presented with spontaneous CSF rhinorrhea and was treated by endoscopic skull base defect repair with thecoperitoneal shunt placement. CSF rhinorrhea can be due to traumatic or nontraumatic causes. Traumatic can be either due to head injuries causing skull base fractures or due to iatrogenic causes. Spontaneous leaks could be associated with or without raised ICP. High-pressure leaks could account up to 45% of the nontraumatic CSF rhinorrhea.[15] Sustained increase in ICP causes bony erosion and creation of an osteodural defect in pneumatized parts of the skull base such as cribriform plate, craniopharyngeal canal, sella, and spheno-occipital synchondrosis leading to CSF leak.[7],[15] CSF leaks in these cases have been postulated to represent a manifestation of benign intracranial hypertension or pseudotumor cerebri.[16],[17],[18],[19] In our case also CSF leak was associated with raised ICP with no evidence of trauma or infection. This could be an underlying benign ICP with or without congenital defect.

Normal pressure leaks represent 55% of the nontraumatic cases of the CSF rhinorrhea.[20],[21] It is hypothesized that the spontaneous leak is due to point erosions in the skull base which occur in normal person as a result of physiologic alterations in CSF pressure with transient increase in ICP up to 80 mm of water lasting for few seconds.[15] Other nontraumatic causes of CSF leak include congenital skull base defects, erosion of the skull base by tumors, infection, mucocele, and following radiation.

CSF diversion in patients with long-standing raised ICP may result in the pneumoventricle by air aspiration through a preexisting congenital or iatrogenic skull base erosion/fistula.[3] These fistulous sites/erosion points are plugged by scarred meninges or gliotic brain which open up due to a drop in ICP causing inward flow of air. This air is prevented from escaping by temporarily resealing of meningeal cicatrix and this cycle repeatedly happens, resulting in tension pneumoventricle (ball valve mechanism). Shunts by their siphon effect can create significant negative ICP drop which ranges from −30 to −155 mm of water, and sometimes as low as −440 mm of water.[2],[5] Pneumatocele is located close to the site of fistulae and more common in the temporal lobe. In our case also there might have been a sustained negative pressure caused by the thecoperitoneal shunt without anti-siphon device.

Pneumoventricle presents usually with symptoms and signs of raised ICP such as a recurrent headache with vomiting, impairment of consciousness, seizures, memory disturbances, and gait disturbance. Sometimes, patients present with acute or chronic meningitis. Intracranial splashing sounds called "bruit hydroaerique" are characteristic in some patients. Similarly, our patient also presented with memory disturbances and cognitive impairment during the second presentation.

The delay from CSF shunting to the development of pneumocephalus may vary from a week up to 5 years.[7],[22] The usage of high-pressure shunts and antisiphon devices have been recommended by some authors to prevent this complication.[1],[2],[23] Our routine policy is to place Chhabra standard adult thecoperitoneal shunt with no anti-siphon device. However, anti-siphon device has advantages of preventing over-drainage of CSF, and the reservoir gives access to check the patency of the shunt system. We have seen an increased risk of shunt obstruction with anti-siphon device. We had 42 cases who underwent Lumbar-peritoneal (LP) shunts without anti-siphon device in the past 5 years and none of them presented with shunt obstruction or shunt-related morbidity other than shunt migration (five patients) and abdominal pseudocyst (two patients). Programmable shunt provides the benefit of adjusting the pressure setting according to the ventricular pressure. We routinely do not use programmable LP shunts as ours is a resource-limited center with most of the patients coming from low-socioeconomic strata.

Prevention of infection, treatment of raised ICP, aspiration of pneumoventricle, closure of fistula, and removal of shunt tube are the keys to successful management of tension pneumoventricle secondary to CSF fistula.[23] Broad-spectrum antibiotics are used after shunt removal, but its prophylactic usage is debated.[1],[5],[23] Removal of the shunt tube relieves the sustained negative pressure which may cause recurrent pneumoventricle/pneumocephalus. Postshunt removal a temporary CSF diversion is preferred by some authors, especially, if the infection is doubted clinically or confirmed.[1],[2],[23]

In our case, as there was dislodgement of fat-fascia graft, repacking was done followed by aspiration of pneumoventricle underwater seal and thecoperitoneal shunt was removed. We feel the tension pneumoventricle caused air to dissect into the right temporal lobe region under pressure forming the temporal pneumatocele. The shunt was removed to alleviate negative pressure gradient as it was nonprogrammable shunt with no anti-siphon device. The patient had complete resolution of symptoms after the procedure. This makes us think that we should probably reconsider the usage of anti-siphon device and also a pedicled flap to repair the skull base defects. A programmable valve may be the best choice in financially affordable patients. In patients with normal/moderately high ICP (25 cm of water), a temporary lumbar drain can be considered for few days until the defects heal thus preventing the recurrent CSF leaks.


  Conclusion Top


Although it is a rare entity, tension pneumoventricle should be considered in patients who have undergone CSF diversion procedures along with anterior skull base repair. Sometimes, it can occur as a delayed complication which may lead to acute neurological deterioration and sudden death. Hence, prompt diagnosis is necessary for timely intervention and prevention.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Tuǧcu B, Tanriverdi O, Günaldi O, Baydin S, Postalci LS, Akdemir H, et al. Delayed intraventricular tension pneumocephalus due to scalp-ventricle fistula: A very rare complication of shunt surgery. Turk Neurosurg 2009;19:276-80.  Back to cited text no. 1
    
2.
Ruge JR, Cerullo LJ, McLone DG. Pneumocephalus in patients with CSF shunts. J Neurosurg 1985;63:532-6.  Back to cited text no. 2
    
3.
Horton DD, Pollay M, Reynolds AF Jr. Intraventricular pneumocephalus secondary to subcutaneous emphysema: A case report. Neurosurgery 1984;15:557-8.  Back to cited text no. 3
    
4.
Perrin RG, Bernstein M. Tension pneumoventricle after placement of a ventriculoperitoneal shunt: A novel treatment strategy. Case report. J Neurosurg 2005;102:386-8.  Back to cited text no. 4
    
5.
Jimenez-Jimenez E, Martí SS, Villas MV. Tension pneumocephalus related to radiotherapy for nasopharyngeal carcinoma. Case Rep Oncol Med 2014;2014:327380.  Back to cited text no. 5
    
6.
Aoyama I, Kondo A, Nin K, Shimotake K. Pneumocephalus associated with benign brain tumor: Report of two cases. Surg Neurol 1991;36:32-6.  Back to cited text no. 6
    
7.
Kawajiri K, Matsuoka Y, Hayazaki K. Brain tumors complicated by pneumocephalus following cerebrospinal fluid shunting – Two case reports. Neurol Med Chir (Tokyo) 1994;34:10-4.  Back to cited text no. 7
    
8.
Gönül E, Izci Y, Sali A, Baysefer A, Timurkaynak E. Subdural and intraventricular traumatic tension pneumocephalus: Case report. Minim Invasive Neurosurg 2000;43:98-101.  Back to cited text no. 8
    
9.
Garg N, Devi I, Dua R, Arivazhagan A. Tension pneumoventricle following exposure of shunt chamber. Br J Neurosurg 2008;22:121-2.  Back to cited text no. 9
    
10.
Radhziah S, Lee CK, Ng I. Tension pneumoventricle. J Clin Neurosci 2006;13:881-3.  Back to cited text no. 10
    
11.
Ruiz-Juretschke F, Mateo-Sierra O, Iza-Vallejo B, Carrillo-Yagüe R. Intraventricular tension pneumocephalus after transsphenoidal surgery: A case report and literature review. Neurocirugia (Astur) 2007;18:134-7.  Back to cited text no. 11
    
12.
Satapathy GC, Dash HH. Tension pneumocephalus after neurosurgery in the supine position. Br J Anaesth 2000;84:115-7.  Back to cited text no. 12
    
13.
Little JR, MacCarty CS. Tension pneumocephalus after insertion of ventriculoperitoneal shunt for aqueductal stenosis. J Neurosurg 1976;44:383-5.  Back to cited text no. 13
    
14.
Rizzoli HV, Hayes GJ, Steelman HF. Rhinorrhea and pneumocephalus; surgical treatment. J Neurosurg 1954;11:277-83.  Back to cited text no. 14
    
15.
Yadav YR, Parihar V, Janakiram N, Pande S, Bajaj J, Namdev H, et al. Endoscopic management of cerebrospinal fluid rhinorrhea. Asian J Neurosurg 2016;11:183-93.  Back to cited text no. 15
  [Full text]  
16.
Schlosser RJ, Woodworth BA, Wilensky EM, Grady MS, Bolger WE. Spontaneous cerebrospinal fluid leaks: A variant of benign intracranial hypertension. Ann Otol Rhinol Laryngol 2006;115:495-500.  Back to cited text no. 16
    
17.
Owler BK, Allan R, Parker G, Besser M. Pseudotumour cerebri, CSF rhinorrhoea and the role of venous sinus stenting in treatment. Br J Neurosurg 2003;17:79-83.  Back to cited text no. 17
    
18.
Al-Sebeih K, Karagiozov K, Elbeltagi A, Al-Qattan F. Non-traumatic cerebrospinal fluid rhinorrhea: Diagnosis and management. Ann Saudi Med 2004;24:453-8.  Back to cited text no. 18
    
19.
Schlosser RJ, Bolger WE. Spontaneous nasal cerebrospinal fluid leaks and empty sella syndrome: A clinical association. Am J Rhinol 2003;17:91-6.  Back to cited text no. 19
    
20.
Lopatin AS, Kapitanov DN, Potapov AA. Endonasal endoscopic repair of spontaneous cerebrospinal fluid leaks. Arch Otolaryngol Head Neck Surg 2003;129:859-63.  Back to cited text no. 20
    
21.
Banks CA, Palmer JN, Chiu AG, O'Malley BW Jr., Woodworth BA, Kennedy DW, et al. Endoscopic closure of CSF rhinorrhea: 193 cases over 21 years. Otolaryngol Head Neck Surg 2009;140:826-33.  Back to cited text no. 21
    
22.
Davis DH, Laws ER Jr., McDonald TJ, Salassa JR, Phillips LH 2nd. Intraventricular tension pneumocephalus as a complication of paranasal sinus surgery: Case report. Neurosurgery 1981;8:574-6.  Back to cited text no. 22
    
23.
Sasani M, Ozer FA, Oktenoglu T, Tokatli I, Sarioglu AC. Delayed and isolated intraventricular tension pneumocephalus after shunting for normal pressure hydrocephalus. Neurol India 2007;55:81-2.  Back to cited text no. 23
[PUBMED]  [Full text]  


    Figures

  [Figure 1][Figure 2][Figure 3]