Lack of an association between alopecia areata and visceral or hematopoietic cancers

To the Editor: Alopecia areata (AA) is a polygenic, patchy nonscarring hair loss that presents on the scalp and body that drastically affects patients' quality of life.1 The pathogenesis of AA remains elusive, though T-lymphocyte–mediated inflammation and various environmental stressors play a role. The association between AA and various autoimmune diseases has been explored in several studies.1 Recently, studies found lower rates of nonmelanoma skin cancers and a trend toward decreased melanoma among AA patients.

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Recurrence of genital aphthosis in girls: A retrospective analysis

To the Editor: Genital aphthosis in girls is a rare, underrecognized condition characterized by genital ulceration after an acute systemic illness.1,2 The aphthae often are associated with severe dysuria and emotional distress in this young, adolescent population. We sought to identify disease recurrence by reviewing clinical records from January 1997 through August 2015. Institutional review board approval was obtained (IRB# 15-008638, December 2015).

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Prevalence of pediatric alopecia areata among 572,617 dermatology patients

To the Editor: The authors initiated this retrospective analysis to evaluate the prevalence, age, and sex of pediatric patients with alopecia areata (AA) and the impact that pediatric AA has on a typical dermatology practice. Billing data from Leavitt Medical Associates of Florida, doing business under the name Advanced Dermatology and Cosmetic Surgery, was collected from offices throughout Florida and Ohio, and 572,617 dermatology patients were identified. The study population included 71,951 pediatric patients (1-17 years of age): 33,800 boys and 37,791 girls.

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Spectrum of orocutaneous disease associations

The oral cavity and cutaneous organ systems share a close embryologic origin. Therefore, there are numerous dermatologic conditions presenting with concomitant oral findings of which the dermatologist must be aware. The second article in this continuing medical education series reviews inflammatory orocutaneous conditions and a number of genodermatoses. It is essential for dermatologists to be familiar with oral cavity manifestations associated with dermatologic diseases for prompt diagnosis, management, and appropriate referral to stomatology and dentistry.

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Onychophagia and onychotillomania can be effectively managed

To the Editor: We greatly appreciate the commentary by Lipner and Scher.1 We agree that our patients would benefit from prompt treatment to reduce shame and prevent irreversible nail damage. Herein, we present our clinical pearls using pharmacotherapy, stimulus control, habit-reversal training (HRT), and cognitive behavioral and aversion therapy. We often combine psychotherapies such as HRT and stimulus control. Six or more sessions are typically required. We have treated several cases of onychophagia and onychotillomania with N-acetylcysteine 1200-2400 mg/day.

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October iotaderma (#284)

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Comment on “Psychocutaneous disease: Clinical perspectives”

To the Editor: Kuhn et al1 are to be commended for writing this informative review on psychocutaneous disease. In this manuscript, they delineate common psychiatric conditions with skin manifestations including delusional, factitious, obsessive-compulsive, and eating disorders; psychogenic pruritus; cutaneous sensory (pain) syndromes; posttraumatic stress disorder; and sleep-wake disorders. They appropriately describe the important role fingernails play in removing organisms during delusional infestations and describe patients with factitious skin disorder creating well-demarcated geometric erosions.

http://ift.tt/2yb9kaY

Smoke-evacuating cautery pencils for dermatologic surgery

Potential health risks may exist related to particulates and volatile chemicals in electrosurgical smoke.1 Although particulate matter is effectively filtered by specialized masks such as N-95 masks, volatile chemicals are not.1 Standard surgical masks provide no protection. Further, handheld smoke evacuation with stand-alone units requires an assistant to carefully follow the motions of the surgeon while reliably holding the evacuation tube at the correct distance from the cautery tip (≤2 in)2 without compromising the visual field.

http://ift.tt/2wMxiI0

Recurrence, evolution, and re-excision of moderately dysplastic nevi

To the Editor: I read with great interest the fascinating and valuable article by Hiscox et al on recurrence of moderately dysplastic nevi (MDN).1 The authors argue that their findings "support the conclusion of the Pigmented Lesion Subcommittee that incompletely excised MDN do not require re-excision." While the authors' study indeed adds to the literature, and supports the findings of another recent study2 assessing a similar clinical question, several important caveats should be noted.

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CME examination

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Approach to moderately dysplastic nevi with positive histologic margins

To the Editor: We are grateful to Dr Kantor for his thoughtful and detailed review of our paper.1 Our goal was to contribute to the literature regarding moderate dysplastic nevi (DN), and we showed that 147 such nevi with positive histologic margins showed a recurrence rate of only 4%.2 We agree that larger studies are needed and are grateful that they are underway. Dr Kantor is correct in pointing out that the majority of these moderate DNs were biopsied with the intent to excise, and we agree that our data are not applicable to partially sampled lesions because partial sampling was not the goal of our study.

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Oral tofacitinib monotherapy in Korean patients with refractory moderate-to-severe alopecia areata: A case series

To the Editor: Recent reports document successful treatment of alopecia areata (AA) with tofacitinib.1-5 However, long-term data using tofacitinib monotherapy is still sparse, and we are unaware of the quality of treatment in persons of Asian decent. We report the results of extended tofacitinib monotherapy in adult Korean patients with moderate-to-severe AA.

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Histopathologic features of melanoma in difficult-to-diagnose lesions: A case-control study; methodological issues

To the Editor: We read with great interest the article authored by Gonzalez et al that was published in the Journal of the American Academy of Dermatology in 2017.1 The authors aimed to measure the accuracy of histopathologic features in difficult-to diagnose melanocytic tumors and the interobserver agreement of those features. They constructed a prediction model and found that asymmetry, single-cell melanocytosis, solar elastosis, pagetoid melanocytosis, and broad surface diameter were the most predictive factors of outcome studied.

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Iotaderma #285

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Reply to: “Histopathologic features of melanoma in difficult-to-diagnose lesions: A case-control study; methodological issues”

To the Editor: I thank Drs Ayubi and Safiri1 for their comments regarding our recent article on the accuracy of different histopathologic features of melanoma in difficult-to-diagnose melanocytic neoplasms.2 I would like to emphasize that this was an exploratory hypothesis-generating research project designed to identify which histopathologic attributes were most likely to be of value in designing a diagnostic algorithm for the difficult melanocytic neoplasm. Ayubi and Safiri recommend (1) additional validation studies and (2) better demonstration of temporality between independent and dependent variables.

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Frequent skin examinations in patients with actinic keratoses: Ethical, financial, and moral implications

In many disputes, the 2 parties in disagreement can "meet each other halfway" and reach a pragmatic solution that may not be perfect but is acceptable to both. When disagreements occur in the context of the physician-patient relationship, there are inevitably ethical issues or principles to be considered in arriving at a solution. In addition, the competing interests of others may need to be considered.

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Mitigation or prevention of mild hair dye contact dermatitis after pretreatment with clobetasol foam

Nearly 40% of commercial hair dye users develop allergic contact dermatitis (ACD).1 Weak ACD reactions might be augmented with repeated exposure.2 Thus, stopping the cycle early might not only mitigate symptoms but also prevent progression.

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CME examination

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Editorial Board

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Folate and phototherapy: What should we inform our patients?

Ultraviolet (UV) degradation of folate has been studied in vitro and in vivo, but comprehensive reviews of the subject and recommendations for supplementing folate are lacking, especially for women of childbearing age, in whom decreases in folate predisposes newborns to neural tube defects.

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Effect of a high-cholesterol diet on lipoprotein metabolism and xanthoma formation in rabbits

Summary

Background

Xanthelasma is the most common type of cutaneous xanthoma and often occurs on the eyelids. Xanthoma has been reported to be highly correlated with abnormal lipoprotein metabolism.

Aims

In this study, we wanted to investigate the effects of a high-cholesterol diet on xanthoma formation and lipoprotein metabolism in rabbits.

Methods

In animals fed with high-cholesterol diet, deteced plasma lipid [ie, total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (L-DLC)] levels and pathology of xanthoma.

Results

Plasma lipid levels were dramatically elevated within 8 weeks. In addition, high dietary cholesterol promoted xanthoma formation on the napex. Microscopic examination showed that foam cells laden with cholesterol deposits accumulated around the dermal capillaries and cutaneous appendages within the skin of the napex.

Conclusion

These findings indicate a critical role for a high-cholesterol diet in the dysregulation of lipoprotein metabolism and the development of xanthoma in rabbits. The results suggest that abnormal lipid metabolism may increase the occurrence of xanthoma.

http://ift.tt/2kEvYW5

The preadolescent acne microbiome: A prospective, randomized, pilot study investigating characterization and effects of acne therapy

Abstract

Background/Objectives

Acne, a common pediatric disease, tends to be more comedonal in preadolescents, whereas older individuals are more likely to have inflammatory lesions in addition to comedones. Thus the microbiome of preadolescents may be different. In this pilot study we aimed to characterize the preadolescent acne microbiome, compare the microbiome in preadolescents with and without acne, and investigate changes in the microbiome after topical treatment with benzoyl peroxide or a retinoid in a small cohort of preadolescents.

Methods

Participants were 7-10 years of age with (intervention group) or without (control group) acne and were recruited during routine outpatient dermatology visits. Baseline questionnaires, physical examination, and pore strip application were performed for all participants. Intervention group participants were randomized to receive topical therapy with benzoyl peroxide 5% gel or cream or tretinoin 0.025% cream. Participants with acne were followed up 8-10 weeks later and pore strip application was repeated.

Results

Preadolescents with acne were colonized with a greater diversity of cutaneous bacteria than controls and the most commonly identified bacterium was Streptococcus. The number of bacterial species and phylogenetic diversity decreased after treatment with benzoyl peroxide and tretinoin.

Conclusion

The predominant bacteria in microbiome studies of adult acne is Propionibacterium, whereas in this pediatric population we saw a lot of Streptococcus bacteria. After treatment, the microbiomes of intervention group participants more closely resembled those of control group participants.

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Pediatric keloids: A 6-year retrospective review

Abstract

Background/Objectives

Keloids are reportedly rare at the extremes of life. We sought to describe the epidemiology of pediatric keloids seen at the plastic surgery outpatient department of the University College Hospital, Ibadan.

Methods

We retrospectively reviewed all children younger than 19 years who presented with nonburn keloids between 2008 and 2014. Data were obtained on age; duration, size, and location of the keloid; family history; mode of treatment; and outcome. Outcome variables were recurrence and wound complications. Data were analyzed using the Pearson chi-square test for discreet variables and the independent-sample t test for continuous variables. P < .05 was taken as statistically significant.

Results

Within the review period, 304 patients presented with keloids, of whom 40 (13.1%) were younger than 19 years. There was a female preponderance (n = 23, 57.5%). The mean age at onset of the keloid was 9.3 years (range 3 months-18 years). Thirty (75%) patients had keloids in the head and neck region. Keloids were sporadic in 31 (77.5%) patients. Nineteen (47.5%) patients had multimodal treatment for keloid. The recurrence rate was 20%. Recurrence was significantly associated with the size of the lesion (P = .003).

Conclusion

Keloids during childhood are not rare. More attention should be paid to the management of keloids in this age group.

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Agminated segmental plaque-type blue nevus associated with hypertrichosis and soft tissue hypertrophy: Report of a case and review of the literature

Abstract

Blue nevi are common skin neoplasms that typically present as asymptomatic solitary papules, although they may rarely occur in an agminated configuration. We describe a case of agminated blue nevus in a segmental facial distribution associated with soft tissue hypertrophy and hypertrichosis in a 16-year-old boy and present a review of the literature. Although they are generally considered to be benign, concurrent soft tissue changes occurring within an agminated blue nevus should be investigated thoroughly to exclude alternate diagnoses.

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Perineal groove in female infants: A case series and literature review

Abstract

Background

Perineal groove is a rare congenital malformation that is unknown to many clinicians and is often misdiagnosed. Although it may be self-resolving during childhood, this nonepithelized mucous membrane can pose the risk of local irritation and infection, particularly urinary tract infection.

Methods

A retrospective study of female infants diagnosed with a perineal groove was performed, demographic characteristics and clinical features were analyzed, and a photographic review was conducted.

Results

Five patients with perineal groove were observed in our clinic in 2015-16. The mean age was 14 months. None had symptoms, and no treatment was required. During follow-up of 1 year, all remained asymptomatic.

Conclusions

Our retrospective review suggests that perineal groove may be an underdiagnosed condition. Most cases resolve spontaneously, but confusion in diagnosis may lead to misdiagnosis or misinterpretation of sexual abuse and unnecessary treatments.

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Cold agglutinins in a patient undergoing normothermic cardiac operation with warm cardioplegia

Cold agglutinins are autoantibodies that agglutinate red blood cells at low temperatures, leading to haemagglutination and haemolysis. They are generally of no clinical significance. However, when people with cold agglutinins undergo cardiac operation with hypothermia and cold cardioplegia, they can experience complications. Thus, different perioperative management is required for such patients. We describe a 74-year-old man with cold agglutinins incidentally detected on the preoperative screening test. He had never experienced any complications or developed a haematological disease. Since cold agglutinins were incidentally detected on the preoperative test, a special strategy was used to manage the temperature of cardiopulmonary bypass (CPB) and cardioplegia. He successfully underwent normothermic cardiac operation with warm cardioplegia. A continuous retrograde hyperkalaemic infusion and intermittent antegrade infusion of warm cardioplegia with normothermic CPB is one of the best methods to avoid hypothermia and excessive activity and metabolism of the heart, and to provide a suitable operative field.

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Use of a dynamic gait trainer for a child with thoracic level spinal cord injury

Paediatric spinal cord injury (SCI) can result in permanent mobility impairment with consequences for activity, participation and quality of life. This case documents the effect of an overground supported stepping intervention using a dynamic gait trainer. To our knowledge, there are no published studies on this intervention for children with SCI and similar interventions have only been reported in children at American Spinal Injury Association Impairment Scale (AIS) levels B and C.

A child with a T10 (thoracic level, vertebra 10), AIS level A injury, sustained at 2 years of age, continued to make gains in all areas including participation, activity, body structure and function over the following 4 years. Use of a dynamic gait trainer improved the participant's ability to be active and participate despite lack of further neuromuscular recovery. This novel approach with a commonly available device allowed the child to be active and participate in the absence of neural recovery.

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Early sonographic detection of a succenturiate placenta after IVF in a 42-year-old woman with multiple comorbidities

We present a case of a 42-year-old woman with a pregnancy resulting from in vitro fertilisation and a medical history including two spontaneous abortions, hypercoagulable state and other comorbidities. At 13 4/7 weeks' gestation, during research ultrasonography, the patient was noted to have an anterior succenturiate placental lobe. Following an episode of vaginal bleeding at 21 6/7 weeks, she was diagnosed with a low-lying posterior placental lobe. Velamentous cord insertion, placenta previa and vasa previa were excluded at that time. After elective induction for advanced maternal age at 39 0/7 weeks, arrest of labour and chorioamnionitis resulted in a primary low transverse caesarean section and delivery of a healthy girl at 39 3/7 weeks. Gross examination of the placenta showed an irregular, singleton placenta with an attached succenturiate lobe and a marginally inserting umbilical cord. Both lobes were connected by two vessels.

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Knotted urethral catheter: an unusual complication in adults

Knotting of feeding tubes or urinary catheters has been reported as a rare complication in paediatrics when draining the bladder. This is caused by inserting thin flexible tubes too far in, allowing it to coil. We present a case of a 70-year-old woman who was catheterised during a routine spinal surgery, and the catheter coiled and balloon failed to deflate requiring a cystostopic approach to puncture the balloon and remove it. Awareness of this complication in female catheterisation and education on length of catheter insertion is important to avoid this.

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Metastatic primary seminal vesicle adenocarcinoma: management of a rare tumour with multiagent chemotherapy and hormonal therapy

Primary seminal vesicle adenocarcinoma is one of the rarest genitourinary cancers. The pathogenesis is unknown and clinical manifestations are protean. There is no defined treatment for this disease and various combinations of surgery, chemotherapy, radiation therapy and hormonal therapy have been used in the past. Here, we have reported a primary seminal vesicle adenocarcinoma with hepatic metastases, managed with multiagent chemotherapy (oxaliplatin and 5-fluorouracil based) and androgen ablation (with triptorelin). The key to management of such a case is early diagnosis and multimodal treatment. The reported survival rate continues to be poor even for a localised disease. A consolidated follow-up protocol ensures early diagnosis of recurrent or metastatic disease so that second-line therapy can be started.

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Double PCL sign on sagittal MRI of the knee

Description

A 24-year-old male presented with left knee pain and swelling after a fall six weeks earlier playing football. Clinical examination revealed an antalgic gait and a moderate left knee effusion with tenderness along the medial joint line. Anterior drawer and Lachman tests were positive, suggesting an anterior cruciate ligament (ACL) injury. An MRI scan performed shortly after the injury revealed a large joint effusion and significant acute bone oedema involving the medial tibial condyle. While the posterior cruciate ligament (PCL) was intact, the ACL was elongated and suspicious for an intrasubstance tear. A bucket-handle tear of the medial meniscus was observed with the free fragment seen within the intercondylar notch. This gave rise to the double PCL sign on sagittal view. The patient underwent arthroscopic ACL reconstruction with a hamstring graft, and the medial meniscus was excised as it was unrepairable.

The 'double PCL' sign refers to the...

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Fulminant Bacillus cereus septicaemia with multiple organ ischaemic/haemorrhagic complications in a patient undergoing chemotherapy for acute myelogenous leukaemia

Bacillus cereus is a Gram-positive spore-forming rod widely found in the environment and is thought to be a frequent source of contamination. This micro-organism is reportedly a significant pathogenic agent among immunocompromised individuals. Furthermore, multiple cases of fulminant septicaemia have been reported among individuals receiving chemotherapy for acute myelogenous leukaemia. In some cases, B. cereus septicaemia was associated with multiple haemorrhages. We, herein, describe a patient with an extremely acute course of B. cereus septicaemia characterised by haemorrhage and infarction of multiple organs, which led to his death. Our findings suggest that delayed treatment of B. cereus in patients with haematologic malignancies undergoing chemotherapy may result in extremely poor outcomes; thus, immediate empirical treatment with vancomycin should be considered.

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Juvenile elastoma without germline mutations in LEMD3 gene: A case of Buschke-Ollendorff syndrome?

Abstract

We report the case of a 6-year-old Caucasian girl with clinical and histopathologic features of Buschke-Ollendorff syndrome. Histologic examination of skin lesions showed thick, curly, elastic fibers in the derma. Bone lesions compatible with Buschke-Ollendorff syndrome were found in the girl's mother. Mutations in LEMD3 are pathogenic for Buschke-Ollendorff syndrome. Analysis of all exons and exon-intron junctions of LEMD3 did not reveal any germline mutations.

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Erythrokeratoderma - a manifestation associated with multiple types of ichthyoses with different gene defects

Erythrokeratoderma (OMIM #133200) refers to a group of closely related disorders of cornification manifesting with hyperkeratotic, often transient and migratory, erythematous figurate plaques with sharply demarcated borders that typically develop in early childhood with or without palmoplantar involvement.¹ Erythrokeratodermas have been historically classified into the two main categories: (a) erythrokeratodermia variabilis et progressiva (EKVP, also known as erythrokeratoderma figurata variabilis and Mendes da Costa disease), and (b) progressive symmetric erythrokeratoderma (PSEK, also known as Gottron syndrome).

This article is protected by copyright. All rights reserved.

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The optimal regimen of brentuximab vedotin for CD30+ cutaneous lymphoma: Are we there yet?

Brentuximab vedotin (BV) is an anti-CD30 antibody–drug conjugate that is approved for refractory Hodgkin lymphoma and systemic anaplastic large-cell lymphoma. In the ALCANZA trial, the proportion of CD30+ cutaneous T-cell lymphoma (CTCL) patients achieving an objective response lasting at least 4 months was 56.3% with BV versus 12.5% with conventional therapy (oral methotrexate or bexarotene), and progression-free survival, complete response rate and improvement in symptom burden were significantly improved.¹ As in previous studies, 1.8 mg/kg dose was administered every 3 weeks in this study.^1,2 We routinely use this regimen that has been well studied in clinical trials, starting with 1.8 mg/kg and decrease to 1.2 mg/kg if needed. The safety profile for BV is similar to conventional therapies and although peripheral neuropathy occurs in 67%, it usually resolves or improves after cessation or completion of treatment.¹

This article is protected by copyright. All rights reserved.

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Identifying eustachian tube dysfunction prior to hyperbaric oxygen therapy: Who is at risk for intolerance?

Determine whether specific risk factors, symptoms and clinical examination findings are associated with hyperbaric oxygen therapy (HBOT) intolerance and subsequent tympanotomy tube placement.

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Adjuvant Ipilimumab in Melanoma: Future in Doubt

This hugely expensive regimen has now been eclipsed by the checkpoint inhibitor nivolumab, placing the future of adjuvant ipilimumab under question, argues one expert.
Medscape Medical News

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What to Tell Patients About Tattoo Ink

Dr Arefa Cassoobhoy highlights one of the week's important news stories for primary care.
Medscape Internal Medicine

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Correction: Cutting Edge: Helminth Coinfection Blocks Effector Differentiation of CD8 T Cells through Alternate Host Th2- and IL-10-Mediated Responses [CORRECTIONS]

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Correction: PRMT5-Selective Inhibitors Suppress Inflammatory T Cell Responses and Experimental Autoimmune Encephalomyelitis [CORRECTIONS]

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New Methods To Analyze B Cell Immune Responses to Thymus-Dependent Antigen Sheep Red Blood Cells [NOVEL IMMUNOLOGICAL METHODS]

B cells contribute critically to an effective immune response by producing Ag-specific Abs. During the immune response to so-called "thymus-dependent Ags," activated B cells seek T cell help and form germinal centers. In contrast, thymus-independent Ags generally do not induce germinal center formation. In the germinal center, B cells undergo somatic hypermutation, affinity-based clonal expansion, and differentiation to produce plasma cells and memory B cells. Valuable insight into these processes has been gained by using model hapten–carrier complexes or SRBCs. SRBCs induce robust germinal center formation in mice. Therefore, this Ag is commonly used to study germinal center responses. In contrast to haptenated Ags, thus far it has been difficult to measure the titer of Ag-specific Abs or the expansion of Ag-specific B cells after immunization with SRBCs. We have developed new, simple methods to access these parameters, thus providing new tools to study germinal center and Ab responses.

http://ift.tt/2gaZdyu

Learning the High-Dimensional Immunogenomic Features That Predict Public and Private Antibody Repertoires [SYSTEMS IMMUNOLOGY]

Recent studies have revealed that immune repertoires contain a substantial fraction of public clones, which may be defined as Ab or TCR clonal sequences shared across individuals. It has remained unclear whether public clones possess predictable sequence features that differentiate them from private clones, which are believed to be generated largely stochastically. This knowledge gap represents a lack of insight into the shaping of immune repertoire diversity. Leveraging a machine learning approach capable of capturing the high-dimensional compositional information of each clonal sequence (defined by CDR3), we detected predictive public clone and private clone–specific immunogenomic differences concentrated in CDR3's N1–D–N2 region, which allowed the prediction of public and private status with 80% accuracy in humans and mice. Our results unexpectedly demonstrate that public, as well as private, clones possess predictable high-dimensional immunogenomic features. Our support vector machine model could be trained effectively on large published datasets (3 million clonal sequences) and was sufficiently robust for public clone prediction across individuals and studies prepared with different library preparation and high-throughput sequencing protocols. In summary, we have uncovered the existence of high-dimensional immunogenomic rules that shape immune repertoire diversity in a predictable fashion. Our approach may pave the way for the construction of a comprehensive atlas of public mouse and human immune repertoires with potential applications in rational vaccine design and immunotherapeutics.

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Microbial-Derived Butyrate Promotes Epithelial Barrier Function through IL-10 Receptor-Dependent Repression of Claudin-2 [MUCOSAL IMMUNOLOGY]

Commensal interactions between the enteric microbiota and distal intestine play important roles in regulating human health. Short-chain fatty acids (SCFAs), such as butyrate, produced through anaerobic microbial metabolism represent a major energy source for the host colonic epithelium and enhance epithelial barrier function through unclear mechanisms. Separate studies revealed that the epithelial anti-inflammatory IL-10 receptor α subunit (IL-10RA) is also important for barrier formation. Based on these findings, we examined if SCFAs promote epithelial barrier through IL-10RA–dependent mechanisms. Using human intestinal epithelial cells (IECs), we discovered that SCFAs, particularly butyrate, enhanced IEC barrier formation, induced IL-10RA mRNA, IL-10RA protein, and transactivation through activated Stat3 and HDAC inhibition. Loss and gain of IL-10RA expression directly correlates with IEC barrier formation and butyrate represses permeability-promoting claudin-2 tight-junction protein expression through an IL-10RA–dependent mechanism. Our findings provide a novel mechanism by which microbial-derived butyrate promotes barrier through IL-10RA–dependent repression of claudin-2.

http://ift.tt/2gaZf9A

HVEM Imprints Memory Potential on Effector CD8 T Cells Required for Protective Mucosal Immunity [MUCOSAL IMMUNOLOGY]

Mucosal immunity to reinfection with a highly virulent virus requires the accumulation and persistence of memory CD8 T cells at the site of primary infection. These cells may derive from memory precursor effector cells (MPECs), which are distinct from short-lived effector cells that provide acute protection but are often destined to die. Using respiratory virus infection, we show that herpes virus entry mediator (HVEM; TNFRSF14), a member of the TNF receptor superfamily, provides key signals for MPEC persistence. HVEM-deficient CD8 T cells expanded normally but were skewed away from MPECs with resultant poor development of circulating and lung-resident memory cells. HVEM was selectively expressed on MPECs whereas MPECs deficient in HVEM failed to survive in adoptive transfer recipients. As a consequence, HVEM-deficient recipients failed to afford protection against respiratory reinfection with influenza virus. HVEM therefore represents a critical signal for MPECs and development of protective mucosal CD8 T cell memory.

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The Orphan Nuclear Receptor NR4A3 Is Involved in the Function of Dendritic Cells [MOLECULAR AND STRUCTURAL IMMUNOLOGY]

NR4A3/NOR1 belongs to the NR4A subfamily of the nuclear hormone receptor superfamily, which is activated in a ligand-independent manner. To examine the role of NR4A3 in gene expression of dendritic cells (DCs), we introduced NR4A3 small interfering RNA (siRNA) into bone marrow–derived DCs and determined the expression levels of mRNA and proteins of cytokines, cell surface molecules, NF-B signaling–related proteins, and transcription factors. The expression level of NR4A3 was markedly upregulated by TLR-mediated stimulation in DCs. NR4A3 knockdown significantly suppressed LPS, CpG, or poly(I:C)-mediated upregulation of CD80, CD86, IL-10, IL-6, and IL-12. Proliferation and IL-2 production levels of T cells cocultured with NR4A3 knocked-down DCs were significantly lower than that of T cells cocultured with control DCs. Furthermore, the expression of IKKβ, IRF4, and IRF8 was significantly decreased in NR4A3 siRNA-introduced bone marrow–derived DCs. The knockdown experiments using siRNAs for IKKβ, IRF4, and/or IRF8 indicated that LPS-induced upregulation of IL-10 and IL-6 was reduced in IKKβ knocked-down cells, and that the upregulation of IL-12 was suppressed by the knockdown of IRF4 and IRF8. Taken together, these results indicate that NR4A3 is involved in TLR-mediated activation and gene expression of DCs.

http://ift.tt/2gaZjWS

The Neurobeachin-like 2 Protein Regulates Mast Cell Homeostasis [MOLECULAR AND STRUCTURAL IMMUNOLOGY]

The neurobeachin-like 2 protein (Nbeal2) belongs to the family of beige and Chediak–Higashi (BEACH) domain proteins. Loss-of-function mutations in the human NBEAL2 gene or Nbeal2 deficiency in mice cause gray platelet syndrome, a bleeding disorder characterized by macrothrombocytopenia, splenomegaly, and paucity of α-granules in megakaryocytes and platelets. We found that in mast cells, Nbeal2 regulates the activation of the Shp1-STAT5 signaling axis and the composition of the c-Kit/STAT signalosome. Furthermore, Nbeal2 mediates granule formation and restricts the expression of the transcription factors, IRF8, GATA2, and MITF as well as of the cell-cycle inhibitor p27, which are essential for mast cell differentiation, proliferation, and cytokine production. These data demonstrate the relevance of Nbeal2 in mast cells above and beyond granule biosynthesis.

http://ift.tt/2i1oOdu

Anti-Inflammatory Role of Langerhans Cells and Apoptotic Keratinocytes in Ultraviolet-B-Induced Cutaneous Inflammation [INNATE IMMUNITY AND INFLAMMATION]

UV radiation, particularly UVB, is the major risk factor for the induction of skin cancer, and it induces skin inflammation and immunosuppression. Although reports documented that Langerhans cells (LCs) play various roles in photobiology, little is known about whether they contribute to UVB-induced cutaneous inflammation. Recently, the anti-inflammatory effect of apoptotic cells was noted. This study focuses on the roles of LCs and apoptotic cells in UVB-induced cutaneous inflammation. We show that LCs are essential for resolution of UVB-induced cutaneous inflammation. Administration of quinolyl-valyl-O-methylaspartyl-[2,6-difluophenoxy]-methyl ketone, a broad-spectrum caspase inhibitor with potent antiapoptotic properties, inhibited the formation of UVB-induced apoptotic cells and aggravated UVB-induced cutaneous inflammation in wild-type mice. In contrast, exacerbation of UVB-induced cutaneous inflammation following quinolyl-valyl-O-methylaspartyl-[2,6-difluophenoxy]-methyl ketone administration was not observed in LC-depleted mice. These results suggest that the interaction between LCs and apoptotic cells is critical for resolution of UVB-induced cutaneous inflammation. Interestingly, UVB-induced apoptotic keratinocytes were increased in LC-depleted mice. In addition, we revealed that UVB-induced apoptotic keratinocytes were phagocytosed by LCs ex vivo and that prolongation of UVB-induced cutaneous inflammation following treatment with Cytochalasin D, an inhibitor of phagocytosis, was partially attenuated in LC-depleted mice. Collectively, our findings demonstrate that the interaction between LCs and apoptotic cells, possibly via LC-mediated phagocytosis of apoptotic keratinocytes, has an essential anti-inflammatory role in the resolution of UVB-induced cutaneous inflammation.

http://ift.tt/2gaYRYG

Activated Protein C Attenuates Severe Inflammation by Targeting VLA-3high Neutrophil Subpopulation in Mice [INNATE IMMUNITY AND INFLAMMATION]

The host injury involved in multiorgan system failure during severe inflammation is mediated, in part, by massive infiltration and sequestration of hyperactive neutrophils in the visceral organ. A recombinant form of human activated protein C (rhAPC) has shown cytoprotective and anti-inflammatory functions in some clinical and animal studies, but the direct mechanism is not fully understood. Recently, we reported that, during endotoxemia and severe polymicrobial peritonitis, integrin VLA-3 (CD49c/CD29) is specifically upregulated on hyperinflammatory neutrophils and that targeting the VLA-3^high neutrophil subpopulation improved survival in mice. In this article, we report that rhAPC binds to human neutrophils via integrin VLA-3 (CD49c/CD29) with a higher affinity compared with other Arg-Gly-Asp binding integrins. Similarly, there is preferential binding of activated protein C (PC) to Gr1^highCD11b^highVLA-3^high cells isolated from the bone marrow of septic mice. Furthermore, specific binding of rhAPC to human neutrophils via VLA-3 was inhibited by an antagonistic peptide (LXY2). In addition, genetically modified mutant activated PC, with a high affinity for VLA-3, shows significantly improved binding to neutrophils compared with wild-type activated PC and significantly reduced neutrophil infiltration into the lungs of septic mice. These data indicate that variants of activated PC have a stronger affinity for integrin VLA-3, which reveals novel therapeutic possibilities.

http://ift.tt/2i01ahJ

IL-17A Produced by Innate Lymphoid Cells Is Essential for Intestinal Ischemia-Reperfusion Injury [INNATE IMMUNITY AND INFLAMMATION]

Ischemia-reperfusion (IR) injury to the small intestine following clamping of the superior mesenteric artery results in an intense local inflammatory response that is characterized by villous damage and neutrophil infiltration. IL-17A, a cytokine produced by a variety of cells in response to inflammatory cytokines released following tissue injury, has been implicated in IR injury. Using Il17a^–/–, Il23r^–/–, and Rorc^–/– mice and administration of anti–IL-17A and anti–IL-23 neutralizing Abs to wild-type mice, we demonstrate that intestinal IR injury depends on IL-17A and that IL-17A is downstream of the binding of autoantibody to ischemia-conditioned tissues and subsequent complement activation. Using bone marrow chimeras, we demonstrate that the IL-17A required for intestinal IR injury is derived from hematopoietic cells. Finally, by transferring autoantibody-rich sera into Rag2c^–/– and Rag2^–/– mice, we demonstrate that innate lymphoid cells are the main producers of IL-17A in intestinal IR injury. We propose that local production of IL-17A by innate lymphoid cells is crucial for the development of intestinal IR injury and may provide a therapeutic target for clinical exploitation.

http://ift.tt/2gaZqBM

Cyclodextrin Reduces Cholesterol Crystal-Induced Inflammation by Modulating Complement Activation [INNATE IMMUNITY AND INFLAMMATION]

Cholesterol crystals (CC) are abundant in atherosclerotic plaques and promote inflammatory responses via the complement system and inflammasome activation. Cyclic oligosaccharide 2-hydroxypropyl-β-cyclodextrin (BCD) is a compound that solubilizes lipophilic substances. Recently we have shown that BCD has an anti-inflammatory effect on CC via suppression of the inflammasome and liver X receptor activation. The putative effects of BCD on CC-induced complement activation remain unknown. In this study, we found that BCD bound to CC and reduced deposition of Igs, pattern recognition molecules, and complement factors on CC in human plasma. Furthermore, BCD decreased complement activation as measured by terminal complement complex and lowered the expression of complement receptors on monocytes in whole blood in response to CC exposure. In line with this, BCD also reduced reactive oxygen species formation caused by CC in whole blood. Furthermore, BCD attenuated the CC-induced proinflammatory cytokine responses (e.g., IL-1α, MIP-1α, TNF, IL-6, and IL-8) as well as regulated a range of CC-induced genes in human PBMC. BCD also regulated complement-related genes in human carotid plaques treated ex vivo. Formation of terminal complement complex on other complement-activating structures such as monosodium urate crystals and zymosan was not affected by BCD. These data demonstrate that BCD inhibits CC-induced inflammatory responses, which may be explained by BCD-mediated attenuation of complement activation. Thus, these findings support the potential for using BCD in treatment of atherosclerosis.

http://ift.tt/2i01cpR

Viral Infection Sensitizes Human Fetal Membranes to Bacterial Lipopolysaccharide by MERTK Inhibition and Inflammasome Activation [INNATE IMMUNITY AND INFLAMMATION]

Chorioamnionitis, premature rupture of fetal membranes (FMs), and subsequent preterm birth are associated with local infection and inflammation, particularly IL-1β production. Although bacterial infections are commonly identified, other microorganisms may play a role in the pathogenesis. Because viral pandemics, such as influenza, Ebola, and Zika, are becoming more common, and pregnant women are at increased risk for associated complications, this study evaluated the impact that viral infection had on human FM innate immune responses. This study shows that a herpes viral infection of FMs sensitizes the tissue to low levels of bacterial LPS, giving rise to an exaggerated IL-1β response. Using an ex vivo human FM explant system and an in vivo mouse model of pregnancy, we report that the mechanism by which this aggravated inflammation arises is through the inhibition of the TAM receptor, MERTK, and activation of the inflammasome. The TAM receptor ligand, growth arrest specific 6, re-establishes the normal FM response to LPS by restoring and augmenting TAM receptor and ligand expression, as well as by preventing the exacerbated IL-1β processing and secretion. These findings indicate a novel mechanism by which viruses alter normal FM immune responses to bacteria, potentially giving rise to adverse pregnancy outcomes.

http://ift.tt/2g8j5SM

Maternal Pregravid Obesity Remodels the DNA Methylation Landscape of Cord Blood Monocytes Disrupting Their Inflammatory Program [IMMUNE REGULATION]

Prepregnancy maternal obesity is associated with adverse outcomes for the offspring, including increased incidence of neonatal bacterial sepsis and necrotizing enterocolitis. We recently reported that umbilical cord blood (UCB) monocytes from babies born to obese mothers generate a reduced IL-6/TNF-α response to TLR 1/2 and 4 ligands compared to those collected from lean mothers. These observations suggest altered development of the offspring's immune system, which in turn results in dysregulated function. We therefore investigated transcriptional and epigenetic differences within UCB monocytes stratified by prepregnancy maternal body mass index. We show that UCB monocytes from babies born to obese mothers generate a dampened response to LPS stimulation compared with those born to lean mothers, at the level of secreted immune mediators and transcription. Because gene expression profiles of resting UCB monocytes from both groups were comparable, we next investigated the role of epigenetic differences. Indeed, we detected stark differences in methylation levels within promoters and regulatory regions of genes involved in TLR signaling in resting UCB monocytes. Interestingly, the DNA methylation status of resting cells was highly predictive of transcriptional changes post-LPS stimulation, suggesting that cytosine methylation is one of the dominant mechanisms driving functional inadequacy in UCB monocytes obtained from babies born to obese mothers. These data highlight a potentially critical role of maternal pregravid obesity-associated epigenetic changes in influencing the function of an offspring's monocytes at birth. These findings further our understanding of mechanisms that explain the increased risk of infection in neonates born to mothers with high prepregnancy body mass index.

http://ift.tt/2gcH7vT

A Chlamydia-Specific TCR-Transgenic Mouse Demonstrates Th1 Polyfunctionality with Enhanced Effector Function [INFECTIOUS DISEASE AND HOST RESPONSE]

Chlamydia is responsible for millions of new infections annually, and current efforts focus on understanding cellular immunity for targeted vaccine development. The Chlamydia-specific CD4 T cell response is characterized by the production of IFN-, and polyfunctional Th1 responses are associated with enhanced protection. A major limitation in studying these responses is the paucity of tools available for detection, quantification, and characterization of polyfunctional Ag-specific T cells. We addressed this problem by developing a TCR-transgenic (Tg) mouse with CD4 T cells that respond to a common Ag in Chlamydia muridarum and Chlamydia trachomatis. Using an adoptive-transfer approach, we show that naive Tg CD4 T cells become activated, proliferate, migrate to the infected tissue, and acquire a polyfunctional Th1 phenotype in infected mice. Polyfunctional Tg Th1 effectors demonstrated enhanced IFN- production compared with polyclonal cells, protected immune-deficient mice against lethality, mediated bacterial clearance, and orchestrated an anamnestic response. Adoptive transfer of Chlamydia-specific CD4 TCR-Tg T cells with polyfunctional capacity offers a powerful approach for analysis of protective effector and memory responses against chlamydial infection and demonstrates that an effective monoclonal CD4 T cell response may successfully guide subunit vaccination strategies.

http://ift.tt/2gaS2Gi

T Cells Regulate Peripheral Naive Mature B Cell Survival by Cell-Cell Contact Mediated through SLAMF6 and SAP [IMMUNE REGULATION]

The control of lymphoid homeostasis is the result of a very fine balance between lymphocyte production, proliferation, and apoptosis. In this study, we focused on the role of T cells in the maintenance/survival of the mature naive peripheral B cell population. We show that naive B and T cells interact via the signaling lymphocyte activation molecule (SLAM) family receptor, SLAMF6. This interaction induces cell type–specific signals in both cell types, mediated by the SLAM-associated protein (SAP) family of adaptors. This signaling results in an upregulation of the expression of the cytokine migration inhibitory factor in the T cells and augmented expression of its receptor CD74 on the B cell counterparts, consequently enhancing B cell survival. Furthermore, in X-linked lymphoproliferative disease patients, SAP deficiency reduces CD74 expression, resulting in the perturbation of B cell maintenance from the naive stage. Thus, naive T cells regulate B cell survival in a SLAMF6- and SAP-dependent manner.

http://ift.tt/2hZP9Zv

An Anti-Inflammatory Role for NLRP10 in Murine Cutaneous Leishmaniasis [INFECTIOUS DISEASE AND HOST RESPONSE]

The role of the nucleotide-binding domain and leucine-rich repeat containing receptor NLRP10 in disease is incompletely understood. Using three mouse strains lacking the gene encoding NLRP10, only one of which had a coincidental mutation in DOCK8, we documented a role for NLRP10 as a suppressor of the cutaneous inflammatory response to Leishmania major infection. There was no evidence that the enhanced local inflammation was due to enhanced inflammasome activity. NLRP10/DOCK8-deficient mice harbored lower parasite burdens at the cutaneous site of inoculation compared with wild-type controls, whereas NLRP10-deficient mice and controls had similar parasite loads, suggesting that DOCK8 promotes local growth of parasites in the skin, whereas NLRP10 does not. NLRP10-deficient mice developed vigorous adaptive immune responses, indicating that there was not a global defect in the development of Ag-specific cytokine production. Bone marrow chimeras showed that the anti-inflammatory role of NLRP10 was mediated by NLRP10 expressed in resident cells in the skin rather than by bone marrow–derived cells. These data suggest a novel role for NLRP10 in the resolution of local inflammatory responses during L. major infection.

http://ift.tt/2gaYVaS

Grb2-Mediated Recruitment of USP9X to LAT Enhances Themis Stability following Thymic Selection [IMMUNE SYSTEM DEVELOPMENT]

Themis is a new component of the TCR signaling machinery that plays a critical role during T cell development. The positive selection of immature CD4⁺CD8⁺ double-positive thymocytes and their commitment to the CD4⁺CD8^– single-positive stage are impaired in Themis^–/– mice, suggesting that Themis might be important to sustain TCR signals during these key developmental processes. However, the analysis of Themis mRNA levels revealed that Themis gene expression is rapidly extinguished during positive selection. We show in this article that Themis protein expression is increased in double-positive thymocytes undergoing positive selection and is sustained in immature single-positive thymocytes, despite the strong decrease in Themis mRNA levels in these subsets. We found that Themis stability is controlled by the ubiquitin-specific protease USP9X, which removes ubiquitin K48-linked chains on Themis following TCR engagement. Biochemical analyses indicate that USP9X binds directly to the N-terminal CABIT domain of Themis and indirectly to the adaptor protein Grb2, with the latter interaction enabling recruitment of Themis/USP9X complexes to LAT, thereby sustaining Themis expression following positive selection. Together, these data suggest that TCR-mediated signals enhance Themis stability upon T cell development and identify USP9X as a key regulator of Themis protein turnover.

http://ift.tt/2ga7HGe

NKG2D Signaling between Human NK Cells Enhances TACE-Mediated TNF-{alpha} Release [INNATE IMMUNITY AND INFLAMMATION]

NK group 2 member D (NKG2D) is a strong NK cell–activating receptor, with engagement by ligands triggering granule release and cytokine production. The function of NKG2D signaling in NK cells has largely been studied in the context of engagement of the receptor by ligands expressed on the surface of target cells. We report that upon activation with IL-12, IL-15, and IL-18 human NK cells express NKG2D ligands of the UL16 binding protein family on the cell surface. NKG2D-ligand interaction between cytokine-stimulated NK cells increases the activity of the metalloprotease TNF-α–converting enzyme. This enhanced TNF-α–converting enzyme activity significantly increases the release of TNF-α and UL16 binding protein from the surface of the NK cells. These results demonstrate that NKG2D signaling is critical for maximal TNF-α release by NK cells. Further, they demonstrate a role for NKG2D-ligand interaction via homotypic NK cell contact in NK cell effector function.

http://ift.tt/2g916LZ

IL-4/IL-13 Signaling Inhibits the Potential of Early Thymic Progenitors To Commit to the T Cell Lineage [IMMUNE SYSTEM DEVELOPMENT]

Early thymic progenitors (ETPs) are endowed with diverse potencies and can give rise to myeloid and lymphoid lineage progenitors. How the thymic environment guides ETP commitment and maturation toward a specific lineage remains obscure. We have previously shown that ETPs expressing the heteroreceptor (HR) comprising IL-4Rα and IL-13Rα1 give rise to myeloid cells but not T cells. In this article, we show that signaling through the HR inhibits ETP maturation to the T cell lineage but enacts commitment toward the myeloid cells. Indeed, HR⁺ ETPs, but not HR^– ETPs, exhibit activated STAT6 transcription factor, which parallels with downregulation of Notch1, a critical factor for T cell development. Meanwhile, the myeloid-specific transcription factor C/EBPα, usually under the control of Notch1, is upregulated. Furthermore, in vivo inhibition of STAT6 phosphorylation restores Notch1 expression in HR⁺ ETPs, which regain T lineage potential. In addition, upon stimulation with IL-4 or IL-13, HR^– ETPs expressing virally transduced HR also exhibit STAT6 phosphorylation and downregulation of Notch1, leading to inhibition of lymphoid, but not myeloid, lineage potential. These observations indicate that environmental cytokines play a role in conditioning ETP lineage choice, which would impact T cell development.

http://ift.tt/2hZP8Vr

Knowledge and care seeking practices for ear infections among parents of under five children in Kigali, Rwanda: a cross-sectional study

Infections affecting the middle ear are a common childhood occurrence. Some cases may present with ear discharge through a tympanic membrane perforation which may heal spontaneously. However, up to 5% or more ...

http://ift.tt/2guLejX

Two case reports of desensitization in patients with hypersensitivity to iron

Iron deficiency anemia is a disease that can significantly compromise a patient's quality of life. Desensitization is a safe and effective treatment option for iron-deficient anemic patients who require intrav...

http://ift.tt/2zdukOD

The Efficacy of Peripheral Opioid Antagonists in Opioid-Induced Constipation and Postoperative Ileus: A Systematic Review of the Literature.

Opioid-induced constipation has a negative impact on quality of life for patients with chronic pain and can affect more than a third of patients. A related but separate entity is postoperative ileus, which is an abnormal pattern of gastrointestinal motility after surgery. Nonselective [mu]-opioid receptor antagonists reverse constipation and opioid-induced ileus but cross the blood-brain barrier and may reverse analgesia. Peripherally acting [mu]-opioid receptor antagonists target the [mu]-opioid receptor without reversing analgesia. Three such agents are US Food and Drug Administration approved. We reviewed the literature for randomized controlled trials that studied the efficacy of alvimopan, methylnaltrexone, and naloxegol in treating either opioid-induced constipation or postoperative ileus. Peripherally acting [mu]-opioid receptor antagonists may be effective in treating both opioid-induced bowel dysfunction and postoperative ileus, but definitive conclusions are not possible because of study inconsistency and the relatively low quality of evidence. Comparisons of agents are difficult because of heterogeneous end points and no head-to-head studies. Copyright (C) 2017 by American Society of Regional Anesthesia and Pain Medicine.

http://ift.tt/2kDAmEN

Bleeding and Neurologic Complications in 58,000 Interventional Pain Procedures.

Background and Objectives: Interventional pain procedures are commonly performed on patients receiving antiplatelet therapy. However, there is limited evidence to support or refute the safety of this practice. The goal of this investigation was to assess the rate of bleeding complications in a large cohort of patients undergoing intermediate- and low-risk pain procedures, with a specific focus on antiplatelet and anticoagulant medication use and baseline coagulation abnormalities. Methods: This is a retrospective cohort study of adult patients undergoing low- and intermediate-risk pain procedures from 2005 through 2014 by the division of pain medicine at a single academic tertiary care center. Baseline characteristics, antiplatelet and anticoagulant medication use, coagulation parameters, and procedural details were extracted from the electronic medical record. The primary outcome was a bleeding-related complication requiring emergency medicine, neurology, or neurosurgical evaluation within 31 days. The secondary outcome was the presence or absence of a periprocedural red blood cell transfusion occurring within 72 hours of needle placement. Results: A total of 58,066 procedures were performed on 24,590 unique patients. Preprocedural aspirin or nonsteroidal anti-inflammatory drug therapy was present for 17,825 procedures (30.7%). Sixteen procedures were associated with perioperative red blood cell transfusion (0.03%), with no difference based on preprocedural nonsteroidal anti-inflammatory drug, including aspirin, or other anticoagulation use (P = 0.107). Five patients (0.009%) had a neurologic complication requiring further evaluation, of which 2 were likely related to procedural bleeding. Conclusions: Bleeding complications are rare in patients undergoing low- or intermediate-risk pain procedures even in the presence of antiplatelet medications. This is consistent with recently released guidelines. Copyright (C) 2017 by American Society of Regional Anesthesia and Pain Medicine.

http://ift.tt/2xwfiGz

Pectoral Fascial (PECS) I and II Blocks as Rescue Analgesia in a Patient Undergoing Minimally Invasive Cardiac Surgery.

Introduction: Patients undergoing minimally invasive cardiac surgery have the potential for significant pain from the thoracotomy site. We report the successful use of pectoral nerve block types I and II (Pecs I and II) as rescue analgesia in a patient undergoing minimally invasive mitral valve repair. Case Report: In this case, a 78-year-old man, with no history of chronic pain, underwent mitral valve repair via right anterior thoracotomy for severe mitral regurgitation. After extubation, he complained of 10/10 pain at the incision site that was minimally responsive to intravenous opioids. He required supplemental oxygen because of poor pulmonary mechanics, with shallow breathing and splinting due to pain, and subsequent intensive care unit readmission. Ultrasound-guided Pecs I and II blocks were performed on the right side with 30 mL of 0.2% ropivacaine with 1:400,000 epinephrine. The blocks resulted in near-complete chest wall analgesia and improved pulmonary mechanics for approximately 24 hours. After the single-injection blocks regressed, a second set of blocks was performed with 266 mg of liposomal bupivacaine mixed with bupivacaine. This second set of blocks provided extended analgesia for an additional 48 hours. The patient was weaned rapidly from supplemental oxygen after the blocks because of improved analgesia. Conclusions: Pectoral nerve blocks have been described in the setting of breast surgery to provide chest wall analgesia. We report the first successful use of Pecs blocks to provide effective chest wall analgesia for a patient undergoing minimally invasive cardiac surgery with thoracotomy. We believe that these blocks may provide an important nonopioid option for the management of pain during recovery from minimally invasive cardiac surgery. Copyright (C) 2017 by American Society of Regional Anesthesia and Pain Medicine.

http://ift.tt/2xvfZzH

A history into genetic and epigenetic evolution of food tolerance: how humanity rapidly evolved by drinking milk and eating wheat.

Purpose of review: Human exposure to wheat and milk is almost global worldwide. Yet the introduction of milk and wheat is very recent (5000-10 000 years) when compared to the human evolution. The last 4 decades have seen a rise in food allergy and food intolerance to milk and wheat. Often described as plurifactorial, the cause of allergic diseases is the result from an interplay between genetic predisposition and epigenetic in the context of environmental changes. Recent findings: Genetic and epigenetic understanding and their contribution to allergy or other antigen-driven diseases have considerably advanced in the last few years. Yet, environmental factors are also quite difficult to identify and associate with disease risk. Can we rethink our old findings and learn from human history and recent genetic studies? Summary: More than one million years separate Homo habilis to today's mankind, more than 1 million years to develop abilities to obtain food by foraging in diverse environments. One million year to adjust and fine-tune our genetic code and adapt; and only 1% of this time, 10 000 years, to face the three biggest revolutions of the human kind: the agricultural revolution, the industrial revolution and the postindustrial revolution. With big and rapid environmental changes come adaptation but with no time for fine-tuning. Today tolerance and adverse reactions to food may be a testimony of adaptation successes and mistakes. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Perioperative point of care ultrasound in ambulatory anesthesia: thinking beyond nerve blocks.

Purpose of review: Ultrasound has become readily available in the perioperative area. In this review, we aim to bring forth some uses of ultrasound beyond that in regional anesthesia. Recent findings: Critical care and emergency physicians have embraced ultrasound in their respective fields. We as anesthesiologists and practitioners of acute care medicine are not immune to this penetration. There is been a lot of recent literature on the various uses of perioperative point of care ultrasound. Our review summarizes the recent data and provides the reader with an overall idea of the uses of ultrasound in the perioperative arena. Summary: Focus towards improving patient outcomes is the goal of all physicians and point of care ultrasound is one modality that can help us manage some common conditions in the perioperative period. Perioperative point of care ultrasound training may soon become a prerequisite for an anesthesiology residency. Copyright (C) 2017 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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Is Pterygopalatine Fossa Injection with Adrenaline an Effective Technique for Better Surgical Field in Fess?

Abstract

Functional endoscopic sinus surgery (FESS) is one of most common surgeries in otorhinolaryngology practice. It is done in the narrow confines of the nasal cavity. Bleeding into the surgical field is a major problem faced by endoscopic surgeons. To assess the effectiveness of pterygopalatine fossa infiltration with lignocaine and adrenaline in controlling surgical field bleeding during endoscopic sinus surgery. A randomized blinded study was done among 68 patients who underwent FESS. Infiltration with 2% lignocaine with 1:80,000 adrenaline was given only on one side and the surgeon was blinded as to which side was infiltrated and he was asked to assess the surgical field using a standard scale. There was statistical significant improvement in surgical field on the infiltrated side (p = 0.001) with almost 25–30% improvement in surgical field on the infiltrated side. The surgical field bleeding also varied with the blood pressure with a positive correlation. There were no complications associated with the procedure. Pterygopalatine fossa infiltration with lignocaine and adrenaline is an effective technique in reducing surgical field bleeding during FESS. It can be combined with nasal decongestion or hypotensive anaesthesia for an optimum surgical field.

http://ift.tt/2wMMjJU

Is Pterygopalatine Fossa Injection with Adrenaline an Effective Technique for Better Surgical Field in Fess?

Abstract

Functional endoscopic sinus surgery (FESS) is one of most common surgeries in otorhinolaryngology practice. It is done in the narrow confines of the nasal cavity. Bleeding into the surgical field is a major problem faced by endoscopic surgeons. To assess the effectiveness of pterygopalatine fossa infiltration with lignocaine and adrenaline in controlling surgical field bleeding during endoscopic sinus surgery. A randomized blinded study was done among 68 patients who underwent FESS. Infiltration with 2% lignocaine with 1:80,000 adrenaline was given only on one side and the surgeon was blinded as to which side was infiltrated and he was asked to assess the surgical field using a standard scale. There was statistical significant improvement in surgical field on the infiltrated side (p = 0.001) with almost 25–30% improvement in surgical field on the infiltrated side. The surgical field bleeding also varied with the blood pressure with a positive correlation. There were no complications associated with the procedure. Pterygopalatine fossa infiltration with lignocaine and adrenaline is an effective technique in reducing surgical field bleeding during FESS. It can be combined with nasal decongestion or hypotensive anaesthesia for an optimum surgical field.

http://ift.tt/2wMMjJU

Dendrimers, Carotenoids, and Monoclonal Antibodies

Monoclonal Antibodies in Immunodiagnosis and Immunotherapy , Vol. 0, No. 0.


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Early-life environmental exposures interact with genetic susceptibility variants in pediatric patients with eosinophilic esophagitis

Publication date: Available online 10 October 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Elizabeth T. Jensen, Jonathan T. Kuhl, Lisa J. Martin, Carl D. Langefeld, Evan S. Dellon, Marc E. Rothenberg
BackgroundAlthough eosinophilic esophagitis (EoE) is associated with certain gene variants, the rapidly increasing incidence of EoE suggests that environmental factors contribute to disease development.ObjectiveWe tested for gene-environment interaction between EoE-predisposing polymorphisms (within TSLP, LOC283710/KLF13, CAPN14, CCL26, and TGFB) and implicated early-life factors (antibiotic use in infancy, cesarean delivery, breast-feeding, neonatal intensive care unit [NICU] admission, and absence of pets in the home).MethodsWe conducted a case-control study using hospital-based cases (n = 127) and control subjects representative of the hospital catchment area (n = 121). We computed case-only interaction tests and in secondary analyses evaluated the combined and independent effects of genotype and environmental factors on the risk of EoE.ResultsCase-only analyses identified interactions between rs6736278 (CAPN14) and breast-feeding (P = .02) and rs17815905 (LOC283710/KLF13) and NICU admission (P = .02) but not with any of the factors examined. Case-control analyses suggested that disease risk might be modifiable in subjects with certain gene variants. In particular, breast-feeding in those with the susceptibility gene variant at rs6736278 (CAPN14) reduced the risk of EoE (adjusted odds ratio, 0.08; 95% CI, 0.01-0.59). Admission to the NICU in those without the susceptibility gene variant at rs17815905 (LOC283710/KLF13) significantly increased the risk of having disease (adjusted odds ratio, 4.83; 95% CI, 1.49-15.66).ConclusionsThe interplay of gene (CAPN14 and LOC283710/KLF13) and early-life environment factors (breast-feeding and NICU admission) might contribute to EoE susceptibility.



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Overexpression of constitutively active MAP3K7 in ameloblasts causes enamel defects of mouse teeth

Publication date: December 2017
Source:Archives of Oral Biology, Volume 84
Author(s): Zhao Jinping, Chu Qing, Song Wenying, Yang Chunyan, Xiang Lili, Shi Yao, Wang Yumin, Xu Zhenzhen, Zhang Li, Gao Yuguang
ObjectiveCompelling evidence suggests that mitogen-activated protein kinases (Mapks) play an important role in amelogenesis. However, the role of transforming growth factor (TGF)-β-activating kinase 1 (Tak1, Map3k7), which is a known upstream kinase of Mapks, during amelogenesis remains to be determined. The aim of this study was to investigate the possible involvement of Map3k7 in amelogenesis.DesignWe generated transgenic mice that produced constitutively active human MAP3K7 (caMAP3K7) under the control of amelogenin (Amelx) gene promoter. Radiography and micro-computed tomography (μCT) analysis was used to detect the radio-opacity and density of the teeth. The enamel microstructure was observed with a scanning electron microscope. Histological analysis was used to observe the adhesion between ameloblasts and residual organic matrix of the enamel. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to analyze the expression of enamel matrix protein.ResultsThe enamel of mandibular molars in caMAP3K7-overexpressing mice displayed pigmentation and a highly irregular structure compared with the wild type littermates. Teeth of transgenic animals underwent rapid attrition due to the brittleness of the enamel layer. The microstructure of enamel, normally a highly ordered arrangement of hydroxyapatite crystals, was completely disorganized. The gross histological appearances of ameloblasts and supporting cellular structures, as well as the expression of the enamel protein amelotin (Amtn) were altered by the overexpression of caMAP3K7.ConclusionsOur data demonstrated that protein expression, processing and secretion occurred abnormally in transgenic mice overexpressing caMAP3K7. The overexpression of caMAP3K7 had a profound effect on enamel structure by disrupting the orderly growth of enamel prisms.



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Baseline lab parameters predicting clinical outcome in melanoma patients treated with ipilimumab - a single center analysis

Abstract

Background

Overall response rates (ORR) for ipilimumab in advanced melanoma are only about 10%. Hence, it is important to explore biomarkers predicting ipilimumab responders.

Objective

We aimed to explore biomarkers in order to predict therapy outcome in melanoma patients who have undergone standard ipilimumab therapy in a real-world setting.

Methods

Databases of cutaneous melanoma patients (n = 52) who had received ipilimumab were reviewed and data collected on patient characteristics and diverse lab parameters. We performed univariate and multivariate statistics including logistic regression analysis and Cox proportional-hazards regression.

Results

Baseline leukocytes, lymphocytes, eosinophils, thrombocytes, neutrophil/lymphocyte ratio, thrombocytes/lymphocyte ratio, eosinophil/lymphocyte ratio, and serum vitamin D levels were not significantly associated with ORR, progression-free survival (PFS) and melanoma-specific survival (MSS). Multivariate analysis confirmed anti PD-1 pre-treatment as significant predictor for ORR following ipilimumab therapy. Low LDH levels and more than 2 ipilimumab cycles turned out to be significant independent predictors for prolonged PFS. Low S100B levels and anti-PD-1 treatment before or after ipilimumab were significant independent predictors for improved MSS. All aforementioned parameters and fecal calprotectin did not turn out to be predictors for ipilimumab-induced autoimmune-related adverse events and autoimmune colitis, respectively.

Conclusions

Low serum LDH before ipilimumab treatment is an independent predictor for improved PFS. Furthermore, low serum S100B is an independent predictor for MSS. The number of ipilimumab cycles (> 2) is significantly associated with prolonged PFS. Pre-treatment calprotectin does not predict the occurrence of autoimmune colitis under ipilimumab therapy.

This article is protected by copyright. All rights reserved.

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Most Common Dermatology Diagnoses to the Emergency Department in the Pediatric population

Abstract

Skin related complaints are a top 10 reason for pediatric presentation to the ED. Older studies and those conducted outside of the US demonstrate wide variability in the frequency of pediatric presentations to the ED for skin complaints, ranging from 4-40% of visits.¹ One study found urticaria to be the most frequent PED dermatological diagnosis, while others found viral exanthema and contact dermatitis to be the most common diagnoses.

This article is protected by copyright. All rights reserved.

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State-of-the-art immunogenicity evaluation in phase 3 confirmatory study (EGALITY) with etanercept biosimilar GP2015

Abstract

Immunogenicity is an important aspect of all biologics. Switching between biological products has triggered intensive discussion on the interchangeability of a biosimilar with its reference medicine, with the main focus being immunogenicity and different perspectives within Europe¹ and the United States.² Given that immunogenicity assay validation and performance characteristics differ from assay to assay, the immunogenicity assay parameters discussed here enable the interpretation of the immunogenicity results.

This article is protected by copyright. All rights reserved.

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More about Molluscum pendulum/acrochordons in Tuberous Sclerosis Complex

Abstract

I thank Dr Baykal for his interest in our recent work about the clinical relevance of molluscum pendulum/acrochordons in patients with tuberous sclerosis complex (TSC) (1).He confirms and expands our own findings (2). He correctly insists that MP are not only located on the (posterior) neck, as was also the case in 2 of the 4 patients with TSC and MP that we reported. More widespread involvement, especially of the lateral and anterior aspect of the neck and the upper back, were frequent in the patients he reports.

This article is protected by copyright. All rights reserved.

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A cross-sectional study of the perceptions about triggering factors in acne patients

Abstract

Acne is a common, inflammatory skin disease of the pilosebaceous unit.¹ Patients often have misconceptions about factors exacerbating acne that may influence their treatment seeking behavior. We conducted a cross-sectional study to investigate the perceptions of patients with acne about triggering factors, and how they may differ among adults and adolescents.

This article is protected by copyright. All rights reserved.

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Percutaneous endoscopic gastrostomy feeding of locally advanced oro-pharygo-laryngeal cancer patients

Publication date: November 2017
Source:Oral Oncology, Volume 74
Author(s): Pyrros Papakostas, Georgia Tsaousi, George Stavrou, Dimitrios Rachovitsas, Gavriil Tsiropoulos, Constantina Rova, Ioannis Konstantinidis, Antonios Michalopoulos, Vasilios Grosomanidis, Katerina Kotzampassi
ObjectivesHead and neck cancer patients commonly suffer from severe malnutrition at the time of tentative diagnosis. Percutaneous Endoscopic Gastrostomy [PEG] feeding is now considered as an efficient tool to reduce nutritional deterioration alongside concurrent treatment. We undertook the challenge to retrospectively evaluate the impact of a commercial, disease-specific, feeding formula [Supportan, Fresenius Kabi, Hellas] versus blenderized family food on nutritional outcome.Materials and methodsThis is a retrospective analysis of prospectively collected nutritional and anthropometric data at the time of PEG placement, at the 8th week [after treatment termination] and at 8 months [6mo of recovery from treatment]. All patients were prescribed a commercial feeding formula.ResultsThe final dataset included 212 patients: 112 received the commercial formula, 69 voluntarily decided to switch into blenderized-tube-feeding, and 31 were prescribed to receive a home-made formula of standard ingredients. The commercial formula seemed to help patients to fight the catabolism of concurrent treatment, since, at the 8mo assessment, both Body Mass index and Fat Free Mass had almost recovered to the values at the time of first diagnosis. Neither group on blenderized or home-made formulas exhibited nutritional improvement, but experienced a significant deterioration throughout the study period, with the home-made formula group being the worst.ConclusionThese findings clearly indicate that home-made and blenderized foods do not adequately support the nutritional requirements of patients with HNC scheduled to receive concurrent CRT treatment.



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Characteristics of the Metabolic Syndrome in the Patients of IBERICAN Study (Identification of the Spanish Population at Cardiovascular and Renal Risk)

Metabolic Syndrome and Related Disorders , Vol. 0, No. 0.


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An exploratory, prospective, open-label trial of ingenol mebutate gel 0.05% for the treatment of external anogenital warts

Abstract

Background

Anogenital warts (AGW) can cause physical discomfort and decreased quality of life. Recent case reports suggest that ingenol mebutate gel might be an effective treatment of AGW.

Objective

To explore primarily the safety, and secondarily the efficacy of ingenol mebutate gel 0.05% in patients with AGW.

Methods

This was an exploratory, open-label, 1-arm trial of ingenol mebutate gel 0.05% administered up to 3 times to patients with AGW. Safety was assessed by occurrence and severity of local skin reactions (LSRs) and treatment-related adverse events (AEs). Efficacy was assessed by complete clearance and reduction in AGW count 14 days after last treatment, and recurrence 12 weeks after clearance.

Results

Of 41 patients enrolled, 40 received treatment and 26 completed the trial. Patients had a median AGW count of 11.0 and AGW duration of 3.0 years at baseline. All patients experienced transient LSRs following treatment with a maximum composite LSR score of 7.5 (on a scale from 0–18). 93% of patients reported treatment-related AEs, most frequently pain (85%) and procedural complications (35%) due to smearing of the gel. 78% of patients took mild analgesics for the pain, typically for 1-2 days following treatment. The majority of AEs were of moderate to severe intensity.

17/39 patients (43.6%) had complete clearance 14 days after last treatment, and AGW count was reduced by 90.9%. There was a tendency towards lower clearance rate in patients with longer duration of AGW. 14/8 patients (57.1%) had AGW recurrence 12 weeks after clearance.

Conclusion

Ingenol mebutate gel was associated with a high number of AEs and withdrawals due to painful local and adjacent skin reactions. Furthermore, it showed promising efficacy in reducing AGW despite a difficult-to-treat population. Optimisation of the formulation is warranted to improve the safety profile of the treatment.

This article is protected by copyright. All rights reserved.

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Time required for a standard sunscreen to become effective following application: a UV photography study

Abstract

Sunscreens are recommended that it should be applied generously (2 mg cm⁻²) half an hour before exposure and reapplied every 2 hours^1,2. It is not, however, always easy to apply in normal life (e.g., children doing outdoor activities at school or beachgoers who have to travel some distance to get to the sea) and in addition, sunscreen can be rubbed off or displaced by friction from clothing during the wait time and lose efficacy.The aim of this study was to determine the time needed for a sunscreen to offer optimal protection from the moment of application.

This article is protected by copyright. All rights reserved.

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Endoscopic versus microscopic approach in attic cholesteatoma surgery

Publication date: Available online 10 October 2017
Source:American Journal of Otolaryngology
Author(s): Giuseppe Magliulo, Giannicola Iannella
PurposeCompare the outcomes of primary exclusive endoscopic ear surgery with those of the microscopic ear surgery in a group of patients affected by attic cholesteatoma.Materials and methodsEighty patients suffered from attic cholesteatoma. Forty patients surgical treated with endoscopic ear surgery and forty patients surgical treated with microscopic ear surgery.ResultsNo statistical differences were found in the parameters analysed (frequency of facial nerve dehiscence, age, disease duration, site of dehiscence) between the endoscopic and microscopic groups indicating a homogeneous selection thus providing a good comparison of the outcomes between the two groups. None of the patients in our survey developed postoperative iatrogenic facial palsy. Graft success rate was 100% in both groups.The overall operation time of endoscopic ear surgery presented a mean value of 87.8min, while in the group of patients treated via microscopic ear surgery a lower mean value of 69.9min was reported.The average healing time was 36.3days for the endoscopic subgroup and 47.8days for the microscopic subgroup.ConclusionThe surgical outcomes of endoscopic ear surgery are comparable to those of the conventional approach in terms postoperative air-conduction, graft success rate and taste sensation. The analysis of postoperative pain and healing times showed better results for EES.The mean operative times of endoscopic ear surgery gradually shortened as the surgeons gained expertise in performing one-hand surgery.



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Outcome of spray cryotherapy plus functional endoscopic sinus surgery on management of healing in nasal polyposis

Publication date: Available online 10 October 2017
Source:American Journal of Otolaryngology
Author(s): Ahmad Rezaeian
BackgroundNasal Polyposis is a benign tumor in nasal or paranasal mucosa, which confronts difficulties in management of healing after treatments with surgery. The aim of this study was to evaluate the effects of Spray Cryotherapy (SCT) on management of healing in patients with nasal polyposis who undergone functional endoscopic sinus surgery.MethodsIn this prospective, clinical trial study, we investigated on 40 patients with nasal polyposis that had indication for functional endoscopic sinus surgery. Patients were divided randomly into two parallel group; cryotherapy (with SCT) and placebo (without SCT). Evaluation of healing after surgery was evaluated with Lund-Mackay and The Sino-nasal outcome test (SNOT-22)-22 scores.ResultPostoperatively, Lund-Mackay and SNOT-22 scores were significantly decreased in both groups, however these scores were significantly lower in cryotherapy group in comparison with placebo group. Also there were no reported serious side effects in both groups.ConclusionIn this paper, we concluded that usage of SCT is an effective and safe method on management of healing and develops recovery rates in patients with nasal polyposis undergoing functional endoscopic sinus surgery.



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Payer database and geospatial analysis to evaluate practice patterns in treating allergy in North Carolina

Publication date: Available online 10 October 2017
Source:American Journal of Otolaryngology
Author(s): Matthew G. Crowson, Kristine Schulz, Alex Ulvila, David L. Witsell
ObjectiveThe objective of this study was to characterize the delivery of allergy care in North Carolina using a large payer charge database and visualization techniques.Study designGeospatial database analysis.SettingNorth Carolina State claims database.Subjects & methodsMedical data from the 2013 FAIR Health National Private Insurance Claims (FH NPIC) database for North Carolina was mined for CPT codes and charges for allergy testing, and for the preparation and provision of allergen immunotherapy. Provider and patient variables were analyzed. Analyses were performed to compare differences in allergy care delivery. A visualization strategy complemented the analytic approach.Results162,037 CPT charge entries were analyzed. Allergy-immunology specialists were the most common provider specialty to perform allergy immunotherapy treatments (68.9%, p<0.05). Among other specialties, there were no significant differences between specialists performing immunotherapy when comparing otolaryngology, family practice, and internal medicine (16.3%; 4.6%; 2.6%; p>0.05). Providers with an M.D. degree were the most common provider type. The three most commonly treated diagnoses were allergic rhinitis variants. Females were more likely to receive allergy treatments versus males (55.9% vs. 51.5%; p<0.001), and were more likely to receive allergy testing (65.3% vs. 34.7%: p<0.005). Internal medicine providers charged higher than any other specialist type (p<0.05) for allergy immunotherapy.ConclusionsUsing a large payer database coupled with visualization techniques was an efficient approach to characterizing the state-wide provision patterns of allergy diagnostic and therapy services in North Carolina. This first tier approach to efficiently exploring questions and describing populations is valuable.



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Landmarks for the preservation of the middle temporal artery during mastoid surgery: Cadaveric dissection study

Publication date: Available online 9 October 2017
Source:American Journal of Otolaryngology
Author(s): Pedram Daraei, Douglas E. Mattox
ImportanceThe middle temporal artery flap is a vascularized periosteal flap that is highly useful for otologic reconstruction including the middle cranial fossa, mastoidectomy defect, and external auditory canal. The course of the artery is close to the external auditory canal and is easily injured during preliminary exposure and elevation of flaps.ObjectivesTo describe the course of the middle temporal artery in relation to the external auditory canal and the superficial temporal artery in order to enhance preservation and use in otologic reconstruction.DesignDissection of preserved, injected cadaveric temporal bones.SettingAnatomical laboratory.ParticipantsSeven cadaveric temporal bones.InterventionTemporal bones were dissected in a planar manner to identify the middle temporal artery along the squamous temporal bone to its origin. The superior border of the external auditory canal was divided, horizontally, into thirds to create three measurement points. Distances between the middle temporal artery and the bony portion of the external auditory canal were then determined.Main outcomes and measuresHorizontal diameter of the external auditory canal, distance from the superior-most border of the external auditory canal to the middle temporal artery, various patterns of the middle temporal artery.ResultsThe middle temporal artery branched from the superficial temporal artery in all specimens. Mean horizontal diameter of the external auditory canal was 9.97mm. Mean distances between the bony portion of the external auditory canal and middle temporal artery for the first, second, and third points along the horizontal diameter of the external auditory canal were 1.57, 2.96, and 4.02mm, respectively. In at least one specimen, the artery dipped into the external auditory canal.Conclusions and relevanceThe middle temporal artery runs closest to the external auditory canal at the anterosuperior border. To preserve the middle temporal artery for use in reconstruction after otologic surgery, the surgeon should avoid dissection superior to the external auditory canal until the artery is positively identified.



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The role of explorative tympanotomy in patients with sudden sensorineural hearing loss with and without perilymphatic fistula

Publication date: Available online 9 October 2017
Source:American Journal of Otolaryngology
Author(s): N.K. Prenzler, B. Schwab, D.M. Kaplan, S. El-Saied
PurposeThe purpose of this study was to describe the role of explorative tympanotomy in patients with Profound Sudden Sensorineural Hearing Loss (SSNHL) without clinical evidence of perilymphatic or labyrinthine fistula and to compare intraoperative findings with the postoperative hearing outcome.Study designRetrospective study of all patients diagnosed with SSNHL who underwent explorative tympanotomy between 2002 and 2005.SettingsTertiary care university-affiliated hospital.Subjects and methodsEighty-two patients were diagnosed with unilateral profound SSNHL and underwent tympanotomy with sealing of the round and oval windows. Values of pure tone audiograms and percentage hearing loss of patients with and without intraoperative diagnosed perilymphatic fistula (PLF) were compared and analyzed.ResultsPLF was diagnosed in 28% cases intraoperatively. In most cases, hearing improved significantly after surgery. Interestingly, patients with PLF had a 2.4 times greater decrease of percentage hearing loss compared to patients without PLF.ConclusionsExplorative tympanotomy seems to be useful in patients with profound SSNHL. Patients with PLF benefit more from the surgical procedure and have better outcome than patients without PLF.



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Identifying eustachian tube dysfunction prior to hyperbaric oxygen therapy: Who is at risk for intolerance?

Publication date: Available online 10 October 2017
Source:American Journal of Otolaryngology
Author(s): Jason E. Cohn, Michael Pfeiffer, Niki Patel, Robert T. Sataloff, Brian J. McKinnon
PurposeDetermine whether specific risk factors, symptoms and clinical examination findings are associated with hyperbaric oxygen therapy (HBOT) intolerance and subsequent tympanotomy tube placement.Materials and methodsA retrospective case series with chart review was conducted from 2007 to 2016 of patients undergoing HBOT clearance at a tertiary care university hospital in an urban city. Eighty-one (n=81) patient charts were reviewed for risk factors, symptoms and clinical examination findings related to HBOT eustachian tube dysfunction and middle ear barotrauma. Relative risk was calculated for each variable to determine risk for HBOT intolerance and need for tympanotomy tube placement. Risk factor, symptom, physical examination and HBOT susceptibility scores were calculated for each patient.ResultsMean risk factor, clinical and HBOT complication susceptibility scores were significantly higher in patients who did not tolerate HBOT compared to patients who tolerated HBOT. Patients reporting a history of otitis media, tinnitus, and prior ear surgery were at a higher risk for HBOT intolerance. Patients reporting a history of pressure intolerance and prior ear surgery were more likely to undergo tympanotomy tube placement. Patients noted to have otologic findings prior to HBOT were at a higher risk for both HBOT intolerance and tympanotomy tube placement.ConclusionsA thorough otolaryngological evaluation can potentially predict and identify patients at risk for HBOT intolerance and tympanotomy tube placement.



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TPF+CCRT vs.CCRT+PF in Locoregionally Advanced Nasopharyngeal Carcinoma

Condition:   Nasopharyngeal Carcinoma
Intervention:   Drug: Induction Chemotherapy（TPF） Followed by Chemoradiotherapy VS Concurrent Chemoradiotherapy Followed by Adjuvant Chemotherapy (PF) in Patients With Locoregionally Advanced NPC
Sponsor:   Sun Yat-sen University
Not yet recruiting

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Depression und Angst

Zusammenfassung

Hintergrund

Es existieren nur wenige Daten zur Prävalenz psychischer Erkrankungen als Komorbiditäten bei HNO-Patienten. Ziel der Untersuchung war es, das Auftreten von 2 der häufigsten psychischen Störungen, der Depression und der Angst, bei Patienten einer ambulanten HNO-Praxis zu prüfen.

Material und Methoden

Während eines 2‑wöchigen Zeitraums wurden 101 konsekutive Patienten mithilfe des Beck-Depressions-Inventars (BDI-II) und des Beck-Angst-Inventars (BAI) im Sinne einer Screeninguntersuchung befragt.

Ergebnisse

Von 97 ausgewerteten Tests wiesen 38 % Hinweise auf das Vorliegen einer psychogenen Problematik bzw. Komorbidität auf. Dabei betrug der Anteil von mittelschweren und schweren depressiven Syndromen, Angststörungen und kombinierten Störungen 11,3 %. Signifikante Unterschiede im Auftreten auffälliger Testergebnisse zwischen den Geschlechtern bzw. bei akuten und chronischen HNO-Erkrankungen fanden sich nicht. Patienten mit cochleovestibulären Erkrankungen wiesen in der vorliegenden Untersuchungsgruppe den höchsten Anteil pathologischer Testergebnisse auf. Erstaunlich hoch war die Zahl im Test auffälliger Patienten mit Bagatellerkrankungen und -störungen sowie chronischen Belüftungsproblemen der Nase und der Nasennebenhöhlen.

Schlussfolgerungen

Für die HNO-Praxis gibt das Wissen um die nennenswerte Prävalenz psychischer Komorbiditäten dem Behandler wichtige Hinweise. Die Testverfahren BDI II und BAI haben sich als gute und einfach anwendbare Hilfsmittel erwiesen.

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Calcium channel blockers for lung function improvement in asthma

Publication date: Available online 9 October 2017
Source:Annals of Allergy, Asthma & Immunology
Author(s): Kam Yu Chiu, Jian Guo Li, Ying Lin
BackgroundFor decades, calcium channel blockers (CCBs) have been believed to play a role in asthma treatment. However, the clinical efficacy of CCBs for lung function improvement in patients with asthma has not been qualitatively evaluated.ObjectiveTo assess the effect of CCBs vs placebo on lung function test results in adults with asthma.MethodsVarious databases were systematically searched to identify all randomized clinical trials with adults with asthma. We aimed to assess the influence of CCBs on forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), peak expiratory flow rate (PEFR), and provocative concentration of bronchoconstrictive agents causing a 20% decrease in FEV1 (PC20) compared with a placebo. All effect estimates were pooled by the generic inverse variance method with random-effects meta-analysis. Subgroup analysis, sensitivity analysis, and heterogeneity investigation were performed.ResultsThirty eligible articles with 301 patients were included in this meta-analysis. Our results revealed that in a standard exercise test CCBs could produce a mean maximal percentage decrease in FEV1 of 11.56% (95% confidence interval, 8.97%–14.16%; P < .001) and an increase in postdose FEV1 by 80 mL (95% confidence interval, 0.02–0.15 mL; P = .01). However, there was no statistical significance for CCBs in postdose FVC, PEFR, or PC20 of histamine and methacholine.ConclusionCCBs may be beneficial for lung function improvement in asthma, especially in exercise-induced asthma. However, there is a lack of evidence for CCBs protecting asthma patients from chemical irritation.



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Characterization of arthralgia induced by PD-1 antibody treatment in patients with metastasized cutaneous malignancies

Abstract

Background

PD-1 antibodies (PD1ab) are increasingly used in metastatic melanoma and other malignancies. Arthralgia is an underestimated side effect of PD-1 antibody treatment with unknown cause. Our aim was to characterize PD1ab-induced arthralgia.

Patients and methods

We retrospectively included patients with metastatic cutaneous malignancies treated with pembrolizumab or nivolumab ± ipilimumab at the National Center for Tumor Diseases (Heidelberg) between 01/2013 and 09/2016. Arthralgia was characterized by laboratory diagnostics, imaging, and if indicated, rheumatologic consultation.

Results

26 of 195 patients (13.3%) developed arthralgia. The median onset of symptoms was 100 days (7–780 days). Most frequently, arthralgia involved large joints (shoulders, knees) in a predominantly symmetrical pattern. Only two patients were seropositive for rheumatoid factor and/or anti-citrullinated protein antibodies. Ten patients developed the clinical picture of arthritis, with seven of them showing synovitis in MRI or PET/CT. Five patients showed inflammation in joints pre-damaged by osteoarthritis. In 11 patients arthralgia could not be specified. The majority of patients was satisfactorily treated with non-steroidal anti-inflammatory drugs (NSAIDs), 23.1% required additional low-dose corticosteroids and only 7.6% of our patients received further immunosuppressive treatment. Patients with arthralgia showed a better treatment response and improved PFS and OS.

Conclusion

Arthralgia is frequent during PD1ab treatment. The clinical picture varies between synovitis of predominantly large joints, progressive osteoarthritis and arthralgia without evident joint damage. Vast majority of cases can be satisfactorily managed by NSAID and/or low-dose corticosteroids.

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Influence of deep neuromuscular block on the surgeonś assessment of surgical conditions during laparotomy: a randomized controlled double blinded trial with rocuronium and sugammadex

British Journal of Anaesthesia, 2017; 119(3): 435–42, DOI 10.1093/bja/aex241

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Gastric emptying for liquids of different compositions in children

Abstract

Background

Pre-operative fasting balances safety against patient discomfort. We compared the gastric emptying profiles of a novel clear, high protein drink against a "traditional" clear and a non-clear fluid.

Methods

We conducted a prospective cross-sectional study with 48 healthy volunteers, eight to 14 yr of age, fasted overnight and without risk factors for abnormal gastrointestinal motility. Subjects were randomized in equal ratio to ingest 296 ml of apple juice, 2% milk or Ensure Clear. The gastric antrum was seen by ultrasound in the right lateral decubitus position at baseline, after ingestion, then every 30 min thereafter until return to baseline or six h. Gastric antral cross-sectional area was measured independently by two anaesthetists, and compared between drinks.

Results

Gastric emptying differed between apple juice, 2% milk and Ensure Clear by analysis of co-variance (P<0.0001), and was faster in males than females (P<0.01). The terminal phase however was similar using interval-censored time to gastric emptying in a survival model (P=0.17) or by comparing proportions with empty stomach vs not empty at 90 min (P=1.0), 120 min (P=0.32), 150 min (P=0.11), 180 min (P=0.76) or 210 min (P=1.0).

Conclusions

Despite early differences, clearance from the stomach of apple juice, 2% milk or Ensure Clear is similar at the terminal phase, which is the period of greatest relevance to preoperative fasting recommendations. The stomach is essentially clear by 3-3.5 h for all three drinks studied. The differentiation between liquids in current guidelines is not supported by this study.

Clinical trial registration

clinicaltrials.gov NCT02938065 http://ift.tt/2yd7RDh.

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Overuse of preoperative laboratory coagulation testing and ABO blood typing: a French national study

Abstract

Background

Following publication of guidelines on routine preoperative tests, the French Society of Anaesthesiology and Intensive Care (SFAR), in association with French national public health insurance, conducted a survey to evaluate adherence to guidelines and the economic consequences.

Methods

Using the French Hospital Discharge Database and National Health Insurance Information system, tests performed during the 30 days before surgery were analysed for two situations: (1) standard laboratory coagulation tests and ABO blood typing in children able to walk and scheduled for tonsillectomy/adenoidectomy; and (2) ABO blood typing in adults before laparoscopic cholecystectomy, thyroidectomy, lumbar discectomy or breast surgery. Guidelines do not recommend any preoperative tests in these settings.

Results

Between 2013 and 2015, a coagulation test was performed in 49% of the 241 017 children who underwent tonsillectomy and 39% of the 133 790 children who underwent adenoidectomy. A similar pattern was observed for ABO blood typing although re-operation rates for bleeding on the first postoperative day were very low (0.12–0.31% for tonsillectomy and 0.01–0.02% for adenoidectomy). Between 2012 and 2015, ABO blood typing was performed in 32–45% of the 1 114 082 patients who underwent one of the four selected procedures. The transfusion rate was very low (0.02–0.31%). The mean cost for the four procedures over the 4 yr period was €5 310 000 (sd €325 000).

Conclusions

Standard laboratory coagulation tests and ABO blood typing are still routinely prescribed before surgery and anaesthesia despite current guidelines. This over-prescription represents a high and unnecessary cost, and should therefore be addressed.

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Death or near-death in patients with obstructive sleep apnoea: a compendium of case reports of critical complications

Abstract

The care of surgical patients with obstructive sleep apnoea (OSA) invokes concerns with safety and liability because of the risk that exists for perioperative death or near-death. The purpose of this review is to analyse the available literature to identify risk factors for perioperative critical complications in patients with OSA. Literature reports were screened for life threatening complications and deaths in surgical patients with OSA. The critical complications were sub-grouped as death/near-death events (death and anoxic brain damage) vs critical respiratory events (CRE)/other events and analysed for various risk factors. Both univariate and multivariate analyses were conducted to identify the potential risk factors.In total, 15 case reports and two medico-legal reports, comprising of 60 total patients with OSA were included in our analysis. Overall, there were 43 deaths or near-death events and 12 critical respiratory events and five other life threatening events. Ten patients (17%) with OSA were undiagnosed before surgery. Only 31% (11/35) were on preoperative continuous positive airway pressure (CPAP), with 36% (4/11) of them continuing CPAP in the postoperative period. The majority of them received a morphine equivalent daily dose less than 10 mg. Eighty percent of the events occurred in the first 24 h and 67% occurred on the general hospital ward.Patients with OSA are at risk of critical complications including death during the initial 24 h after surgery. Morbid obesity, male sex, undiagnosed OSA, partially treated/untreated OSA, opioids, sedatives, and lack of monitoring are risk factors for death or near-death events.

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Successful treatment of community-acquired methicillin-resistant Staphylococcus aureus purulent myopericarditis

A previously healthy 48-year-old active duty man, who had been treated for an elbow abscess 3 weeks earlier, presented to an emergency department in Bahrain with tachycardia, pericardial friction rub and jugular venous distention. Cardiac tamponade was confirmed on transthoracic echocardiogram and he was taken for emergent pericardiocentesis. Pericardial fluid cultures grew community-acquired methicillin-resistant Staphylococcus aureus. Despite ongoing treatment with intravenous vancomycin, he developed a recurrent fibrinous pericardial effusion and constrictive pericarditis requiring pericardiectomy. Though he initially did well postoperatively, he developed drug reaction with eosinophilia and systemic symptoms syndrome in response to vancomycin. He was transitioned to ceftaroline and started on high-dose steroids. He recovered during a week-long admission and was discharged home. Several weeks later at follow-up he was doing well and had resumed moderate intensity exercise.

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Unusual complications from amitriptyline intoxication

Althoughtricyclic antidepressants(TCAs) are frequently prescribed to patients with depression, these drugs can also be misused. A 21-year-old comatose patient was referred to our hospital presenting with ventricular tachycardia. Despite initial treatment including intravascular lipid emulsion, ventricular fibrillation occurred soon after arrival. Venoarterial extracorporeal membrane oxygenation and therapeutic hypothermia were administered. Refractory arrhythmia disappeared on the next day. A high concentration of amitriptyline was identified in his blood samples on arrival. Mechanical bowel obstruction followed after abdominal compartment syndrome caused by anticholinergic effects, and refractory seizure occurred due to TCA intoxication. Although seizure was brought under control with anticonvulsant agents, his Glasgow Coma Scale did not recover to the full score. MRI presented irreversible damage to the bilateral frontal lobe and insula. Amitriptyline has the potential to cause unusual serious complications, such as abdominal compartment syndrome, irreversible central nervous system disability and lethal arrhythmia.

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