Left or right? An Australian study of the laterality of skin cancers

http://bit.ly/2G9we8H

Diagnosis and treatment choices of suspected benign paroxysmal positional vertigo: current approach of general practitioners, neurologists, and ENT physicians

Abstract

Purpose

Benign paroxysmal positional vertigo (BPPV) is a frequently underdiagnosed cause of vertigo, potentially due to the underuse of diagnostic and therapeutic canalith repositioning procedures (CRPs). We aimed to investigate self-reported use of the diagnostic and therapeutic approach to BPPV patients by Lithuanian neurologists, ear, nose, and throat (ENT) physicians, and general practitioners (GPs), and to explore potential reasons for the underuse of the maneuvers.

Methods

Neurologists, ENT physicians, and GPs were invited to complete a written questionnaire focused on diagnostic and therapeutic practices related to BPPV. Between-group differences and associations between responses were analyzed statistically.

Results

In total, 97 neurologists, 85 ENT physicians and 142 GPs (21.1%, 26.8%, and 5.7%, respectively, of all corresponding licensed Lithuanian physicians) completed the questionnaire. 24% of neurologists, 33% ENT physicians and 50% GPs do not perform diagnostic maneuvers for patients with suspected BPPV, and 28%, 61%, and 84%, respectively, do not perform CRPs. Years of clinical experience was a negative predictor of CRP performance [OR 0.97 (95% CI 0.95–0.99), p = 0.001]. Frequent reasons for not performing CRPs were time taken for the procedure, fear of provoking symptoms, and lack of knowledge. All physicians frequently ordered additional imaging or consultations for suspected BPPV and reported prescribing a range of medications.

Conclusions

A significant proportion of Lithuanian neurologists, ENT physicians, and GPs do not employ diagnostic maneuvers and CRPs for BPPV patients, contrary to established guidelines. Lack of expertise and time available is a common culprit that leads to unnecessary drug prescribing and investigation.

http://bit.ly/2G93cpY

Eosinophilic infiltration: an under‐reported histological finding in urticarial vasculitis

Abstract

Background

Urticarial vasculitis (UV) is a clinicopathologic entity in which skin lesions resemble urticaria clinically but last more than 24 hours and resolve with residual purpura. In this study, we evaluated distinguishing histological features of UV from common urticaria to differentiate between these two entities.

Methods

During 1 year, 55 urticaria and 245 UV samples were assessed. The selection criteria for UV included: (1) samples that the histological diagnosis was confirmed by two independent dermatopathologists, (2) the histological diagnosis of UV was inconsistent with the first clinical impression and lesion characteristics.

Results

Of our 245 UV patients, 96% had endothelial swelling, 18% had red blood cell (RBC) extravasation, neutrophilic infiltration was seen in 46.7%, and perivascular, interstitial, and perineural eosinophilic infiltration in 198 (81.8%), 181 (74.2%), and 118 (48.1%), respectively. Among different histological findings, endothelial cell swelling as well as neutrophil around vessels and eosinophilic infiltrations were statistically different between two groups (P‐value ˂ 0.001). Both urticaria and UV samples showed a predominantly lymphocytic infiltration more than 10 cells per high power field (HPF) (98.2% of urticaria, 98.8% of UV), and only two patients (0.8%) with UV had predominant neutrophilic infiltration (more than 10 cells/HPF).

Conclusion

We have found that both urticaria and UV showed a predominantly lymphocytic infiltration along with RBC extravasation, endothelial cell swelling, and fibrin deposition in UV. Moreover, significant perineural, perivascular, and interstitial infiltration of eosinophil in UV lesions compared to urticaria was another point that indicates special contribution of these cells in UV pathogenesis.

http://bit.ly/2G8M7wk

Platelet‐rich plasma and microneedling improves hair growth in patients ofandrogenetic alopecia when used as an adjuvant to minoxidil

Summary

Background

Platelet‐rich plasma (PRP) is a popular procedure for the treatment of androgenetic alopecia (AGA).

Aim

To ascertain the role of minoxidil 5% lotion alone versus minoxidil 5% lotion and PRP versus minoxidil 5% lotion, PRP with microneedling in AGA.

Material and methods

Ninety‐three AGA patients with Hamilton‐Norwood score 1‐5 were grouped into three groups A, B, and C. Patients in group A (control group) were treated with minoxidil 5% lotion twice daily (n = 31), whereas patients in group B underwent treatment with minoxidil 5% lotion twice daily and PRP (n = 31), and group C patients received minoxidil 5% lotion twice daily, PRP, and microneedling (n = 31). Baseline and post‐treatment photographs were taken along with dermoscopic evaluation. Selection of the dermoscopic variables included in the evaluation process was based on the published literature and dermoscopists' expertise and experience. Hair pull test was performed before and during follow‐up.

Results

Post‐treatment, hair pull test was negative in 27 patients (87.1%, P < 0.01) of group C, 20 patients (64.5%, P < 0.05) of group B, and 15 patients (48.4%) of group A. Hair growth was better appreciated in group C (26/31) compared to groups B (17/31)and A (10/31).The patients' self‐satisfaction score on a Likert scale was more than seven (high satisfaction) in 24/31 patients in group C. There was a statistically significant difference between three groups in terms of hair pull test, terminal‐to‐vellus hair ratio, and patient satisfaction score as determined by one‐way ANOVA.

Conclusion

PRP with microneedling is better in comparison with PRP alone or minoxidil monotherapy in patients with AGA.

http://bit.ly/2HDJ3KL

Acute blue finger syndrome: a rare benign cause of acute digit discolouration

Acute blue finger syndrome is a rare benign condition that mimics digital ischaemia. We discuss the case of a 32-year-old woman who presented with a 6hour history of blue discolouration of the middle finger of the right hand, associated with pain and swelling. There was no history of trauma and this was the first time that the patient had experienced these symptoms. Examination found blue discolouration of the digit primarily on the volar aspect with associated swelling. All investigations, including blood tests, X-rays and Doppler scanning, were normal. The symptoms resolved spontaneously within 48 hours. There were no recurrent episodes or long-term sequelae. Patients presenting with an acutely blue finger need rapid assessment to exclude digit ischaemia. Knowledge of this rare benign condition may prevent unnecessary distress, invasive investigations and potentially harmful treatment of a healthy patient.

http://bit.ly/2CS80N6

Examination under anaesthesia of the rectum for removal of gallstones

http://bit.ly/2RXWGcH

Rare case with plethora of upper urinary tract anomalies associated with pelviureteric junction obstruction: a surgical challenge managed with robot assistance

The genitourinary system for reasons unknown is more likely to have birth defects than any other system. The anomaly of collecting system draining the kidney represent mystifying subset of congenital anomalies. Pelviureteric junction obstruction (PUJO) is most common. Chronic obstruction can lead to stasis, urinary infection and stone formation in PUJO. Extrarenal calyces, which is characterised by presence of calyces and renal pelvis outside the renal parenchyma is one of the rare anomalies seen among the collecting system right gonadal vein drains into inferior vena cava. Its altered drainage into right renal vein is rarely seen and reported. Glut of these multiple anomalies in a single case is an extremely rare event. We hereby discuss a case of 40-year-old male patient with combination of all these anomalies and discuss the embryology, presentation and management.

http://bit.ly/2CTrJMt

Primary Ewing sarcoma of the kidney

Primary Ewing sarcoma (ES) or primitive neuroectodermal tumour (PNET) is a rare tumour in adults and primary renal involvement is extremely rare. Patients with renal ES or PNET respond to and would benefit from conventional ES treatment according to ES study protocols. Here, we report a case of a young woman, presenting with right flank pain and haematuria. After ultrasound and CT evaluation, a right middle pole renal mass was detected. The patient underwent radical right nephrectomy, and a grade 4 ES with peritoneal involvement was documented. Subsequently, the patient underwent adjuvant chemotherapy for 5 months. Follow-up 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT scan demonstrated bilateral cervical, hilar, mediastinal and retroperitoneal FDG-avid adenopathies associated with mild right-sided pleural effusion with no metabolic activity, signifying the role of PET/CT scan in tumour restaging.

http://bit.ly/2RU0Lyh

Ileal conduit volvulus: rare complication of urinary diversion

Ileal conduit volvulus is a rare complication of urinary diversion. It has been suggested that various factors including prolonged length of the ileal segment, lack of fixation of the conduit to the peritoneum and failure to close the incised mesentery predispose patients to this complication. We present the case of a 76-year-old man who presented to hospital with severe abdominal pain and oliguria secondary to a volvulus of his ileal conduit. Investigations revealed early acute kidney injury as a result of urinary obstruction which was evident on abdominal CT. The patient subsequently underwent operative repair of the volvulus. Symptoms resolved following the procedure, kidney function improved and the patient was discharged without complication.

http://bit.ly/2CRvLVj

Incidental detection of asymptomatic pneumothorax resulting in a diagnosis of Birt-Hogg-Dube syndrome

http://bit.ly/2RXWydd

Peroneal artery entrapment syndrome (PRAES): a rare cause of ischaemic toes

A 75-year-old man presenting with intermittent discolouration of his left toes was referred to vascular surgery with suspicion of embolic vascular disease. A contrast-enhanced MR angiogram was performed which revealed bilateral dominant peroneal arteries (PRAs). There was evidence of short atherosclerotic stenosis directly at the point where the left PRA passes through the tibiofibular interosseous membrane which we postulate to be the source of the emboli. We present what is believed to be the first reported case of PRA entrapment complicated by distal toe emboli.

http://bit.ly/2CQlMQc

Behavioural changes as the first manifestation of a silent frontal lobe stroke

A 67-year-old man was admitted to our hospital after his relatives found him to have severe personality and behavioural changes. His behaviour was inappropriate and uninhibited. The patient reported no symptoms and he showed poor insight into his own behaviour. Neuroimaging showed an orbitofrontal lesion, due to an infarction of the anterior cerebral artery. The patient was diagnosed with frontal lobe syndrome.

http://bit.ly/2RXWvy3

Double axillary vein variation diagnosed with ultrasound guidance during infraclavicular nerve block intervention

The use of ultrasound guidance increases the safety of peripheral block interventions by allowing anaesthesiologists to simultaneously see the position of block needle, the targeted nerves and surrounding vessels. In this report, we represented three patients diagnosed with double axillary vein variation with ultrasound guidance during infraclavicular nerve block intervention. The patients were scheduled for different types of upper limb surgeries. All patients received infraclavicular nerve block for anaesthetic management. A double axillary vein variation was diagnosed with ultrasound during block interventions. Hydro-location technique was used in all cases and the procedures were completed uneventfully. In the current literature, there is limited number of reports concerning double axillary vein variation. Detailed knowledge of the axillary anatomy is important to avoid complications such as intravascular injection during peripheral nerve block interventions. The use of ultrasound guidance and hydro-location technique should be considered for nerve blocks, especially in the axillary area.

http://bit.ly/2CPtA4D

Pseudomonas meningoencephalitis masquerading as a stroke in a patient on tocilizumab

A previously high-functioning woman presents with clinical and CT features of a subacute ischaemic stroke. Her medical history is relevant for refractory giant cell arteritis on long-term high-dose prednisolone and recent commencement of tocilizumab (interleukin-6 monoclonal antibody). The potential for stroke mimic is considered and a magnetic resonance brain scan is requested. She rapidly deteriorates within 24 hours of admission and unexpectantly dies. An autopsy reveals that she has bilateral pulmonary emboli with lower limb deep vein thrombosis and Pseudomonas meningoencephalitis with frank pus on the brain. We discuss the potential risks of immunosuppression and the role of imaging in the diagnosis of stroke.

http://bit.ly/2RRIeCZ

Intestinal obstruction caused by small bowel adenocarcinoma misdiagnosed as psychogenic disorder

We describe a case of intestinal obstruction caused by a small bowel adenocarcinoma misdiagnosed as psychogenic disorder. A woman in her 40s was admitted to Nagoya City University Hospital with fatigue, anorexia, nausea and vomiting. CT, oesophagogastroduodenoscopy and colonoscopy revealed no signs of organic abnormality in her gastrointestinal tract. As the patient had previously been diagnosed with and treated for depression, her symptoms were suspected to be due to psychogenic disorder. Therefore, she was diagnosed with severe depression and was administered antidepressant agents. Despite intense psychiatric treatment, her symptoms worsened and she was later diagnosed with ileus due to adenocarcinoma in the jejunum. After drainage by insertion of a transnasal decompression tube, a partial jejunum resection was performed. After the resection, the patient's symptoms including fatigue and depression resolved without the use of antidepressant agents.

http://bit.ly/2CPLoNi

Simultaneous presentation of thyroid storm and diabetic ketoacidosis in a previously healthy 21-year-old man

A 21-year-old young man with no history of diabetes or thyroid disease presented to the emergency department with simultaneous thyroid storm and diabetic ketoacidosis. Notable findings on admission were a ventricular rate of 235 beats/min, tachypnoea, tremors, polydipsia and a lack of fever. Due to the unusual constellation of symptoms, diagnosis was only possible after initial laboratory results came back. While the lack of fever is unusual in thyroid storm, diabetic ketoacidosis has previously been reported to suppress fever, and this case supports the occurrence of this phenomenon. This case was highly unusual because the patient had not previously been diagnosed with either type 1 diabetes or Graves' disease.

http://bit.ly/2RRMm5M

Rectal bleeding caused by a syphilitic inflammatory mass

A 47-year-old man presented with fatigue, decrease appetite, abdominal pain and rectal bleeding. His colonoscopy revealed a single, firm, raised, centrally ulcerated mass at the anorectal junction. During this same admission, he was diagnosed with HIV and syphilis, found to have multiple hepatic lesions and positive cerebrospinal fluidvenereal disease research laboratory test (VDRL). Biopsies from both the hepatic lesions and rectal ulcer showed spirochaetes by immunostaining. The initial presentation was felt to be secondary to a rectal inflammatory mass caused by syphilis.

http://bit.ly/2CP5qHJ

Hypocalcaemia and hyponatraemia masquerading the diagnosis of Gitelman syndrome

Gitelman syndrome is the most common renal tubulopathy, recently exhibiting a dramatic rise of incidence in Asia.

A 50-year-old woman presented with vomiting, fatigue and quadriparesis. Physical examination revealed a positive Trousseau sign , hypotonia and areflexia.

Suspecting hypocalcaemia, she was given intravenous 10% calcium gluconate (10 mL administered slowly over 10 min) but her manifestations persisted. An exhaustive laboratory work up revealed the diagnosis of Gitelman syndrome.

The peculiarity of this case however, is entailed in its coexistence with hypocalcaemia and hyponatraemia. In addition, the age of primary presentation being 50 years further culminates its atypicality.

Multiple electrolyte imbalances were corrected by oral and intravenous supplementation and a high sodium-potassium diet was advocated. Administration of spironolactone imposed a pitfall in the management of our patient due to exacerbation of pre-existing hyponatraemia.

On follow-up, her electrolyte profile was stable and corresponding symptoms were alleviated.

http://bit.ly/2RSmzdG

Aortitis and pachymeningitis: an unusual combination in granulomatosis with polyangiitis (myeloperoxidase-associated vasculitis)

Aortitis and pachymeningitis are uncommon manifestations of the antineutrophil cytoplasmic antibody-associated vasculitides, a group of systemic autoimmune diseases mainly affecting small vessels. We present a case of a 71-year-old woman with a remote history of idiopathic chronic granulomatous pachymeningitis complicated with aortic thickening due to autoimmune aortitis.

http://bit.ly/2CTQR5u

Hepatitis in patients with syphilis: an overlooked association

We present the case of a patient who sought treatment for fever and a maculopapular rash involving the trunk, limbs, palms and soles. The patient also presented with hepatomegaly and elevated levels of liver enzymes (with a higher increase of alkaline phosphatase). With the proposal of early syphilitic hepatitis, during the stage of secondary syphilis, a venereal disease research laboratory and Treponema pallidum haemagglutination tests were requested, which confirmed the diagnosis. All altered parameters improved with antibiotic treatment for secondary syphilis. Syphilitic hepatitis is an often overlooked presentation of syphilis and should be considered as a differential diagnosis in patients with elevated levels of liver enzymes and risk factors for syphilis.

http://bit.ly/2RXztXW

Actinomycosis of the omentum with invasion of the abdominal wall, small bowel and transverse colon mimicking malignancy

We report the case of a 59-year-old Russian man who presented with a painless, slow-growing, epigastric mass. CT revealed a large heterogeneous mass within the omentum infiltrating into adjacent tissues. During diagnostic laparoscopy, the omental mass was noted to be firm, raising the suspicion of malignancy. Surgical en-bloc resection of the mass, including the posterior rectus sheath, transverse colon and small bowel, was performed with primary anastomoses at laparotomy. Histological examination was inconsistent with malignancy and revealed the mass to be actinomycosis, confirmed by microscopy and gram staining. Surgical resection was followed by an 8-week course of penicillin and doxycycline antibiotic therapy. This treatment resulted in full clinical and radiological recovery with no complications. Although the clinical and radiological findings, in this case, were highly suspicious of malignancy, abdominal actinomycosis should be considered a differential diagnosis in patients with infiltrative abdominal masses and mild constitutional symptoms.

http://bit.ly/2CM1jfe

Largest giant juvenile fibroadenoma of the breast

Juvenile giant fibroadenoma is a rare benign tumour of the breast accounting for 0.5% of all fibroadenomas. The presentation can be very dramatic and may result in breast deformity and may mimic a rare malignant tumour. It is indeed a great challenge to provide the best treatment for these patients in terms of clinical and psychological care. Meticulous surgical planning is required to ensure a fine balance between adequate resection and the best cosmetic outcome for a developing breast. Every effort should be made to preserve the developing breast irrespective of the size of the tumour as it is in this case. We report the world's largest juvenile fibroadenoma of the breast in a 16-year-old girl who presented to our hospital with a 28x25 cm mass on her left breast in which breast conservation was done. A detailed literature search and management of these lesions are discussed.

http://bit.ly/2RXW86D

Very rare case of synchronous volvulus of the sigmoid colon and caecum causing large-bowel obstruction

Large-bowel obstruction caused by volvulus is potentially life threatening if not managed promptly. Sigmoid colon is the most common site of volvulus followed by caecum. Synchronous double colonic volvulus is an exceedingly rare entity, with only five cases published previously. We present the case of a 77-year-old man with a synchronous sigmoid and caecal volvulus. He underwent total colectomy with ileostomy formation with a view to reverse the ileostomy at a later date.

http://bit.ly/2CQrzFt

Nodular scleritis with strongly positive serum rheumatoid factor: forme fruste rheumatoid arthritis sans arthritis

http://bit.ly/2RTSRoM

Even Short-Term Telmisartan Treatment Ameliorated Insulin Resistance But Had No Influence on Serum Adiponectin and Tumor Necrosis Factor-Alpha Levels in Hypertensive Patients with Metabolic Syndrome

Metabolic Syndrome and Related Disorders, Ahead of Print.


http://bit.ly/2D13mMX

A Guide to Yellow Oral Mucosal Entities: Etiology and Pathology

Abstract

When faced with an uncertain clinical pathosis in the oral cavity, identifying the color of the mucosal lesion helps to narrow down a differential diagnosis. Although less common than red and white lesions, yellow lesions encompass a small group of distinct mucosal pathologic entities. Adipose tissue, lymphoid tissue, and sebaceous glands are naturally occurring yellow constituents of the oral cavity and become apparent with associated developmental or neoplastic lesions. Reactive and inflammatory lesions can create a yellow hue due to purulence, necrosis, and calcification. Some systemic diseases are known to deposit yellow bi-products such as amyloid or bilirubin into the oral mucosa of an affected person, and while not always yellow, unusual entities like verruciform xanthoma and granular cell tumor fall under the umbrella of yellow lesions given their occasional propensity to demonstration the color. This chapter aims to explore the unique group that is yellow lesions presenting in the oral mucosa.

http://bit.ly/2TfsKp2

Tongue Lumps and Bumps: Histopathological Dilemmas and Clues for Diagnosis

Abstract

Exophytic lesions of the tongue encompass a diverse spectrum of entities. These are most commonly reactive, arising in response to local trauma but can also be neoplastic of epithelial, mesenchymal or miscellaneous origin. In most cases, the microscopic examination is likely to provide a straightforward diagnosis. However, some cases can still raise microscopic diagnostic dilemmas, such as conditions that mimic malignancies, benign tumors with overlapping features and anecdotal lesions. A series of "lumps and bumps" of the tongue are presented together with suggested clues that can assist in reaching a correct diagnosis, emphasizing the importance of the clinico-pathological correlations.

http://bit.ly/2G7qH2u

A Rainbow of Colors and Spectrum of Textures: An Approach to Oral Mucosal Entities

http://bit.ly/2FZ9zNl

HPV-Related Papillary Lesions of the Oral Mucosa: A Review

Abstract

Human papillomaviruses (HPVs) are causative of a group of clinically papillary lesions. The HPV-related lesions of the oral cavity include squamous papilloma, condyloma acuminatum, verruca vulgaris, and multifocal epithelial hyperplasia. Benign entities, such as verruciform xanthoma or giant cell fibroma, as well as malignancies, such as papillary squamous cell carcinoma and verrucous carcinoma, may be considered in the clinical and/or histologic differential diagnoses of these lesions. Mechanisms of infection, epidemiology, clinical presentations, histologic features, and differential diagnoses of the HPV-related oral pathologies are discussed. Current concepts of viral transmission, especially as pertaining to lesions in pediatric patients, and the impacts of HPV vaccination are reviewed.

http://bit.ly/2FYoPtE

Candidiasis: Red and White Manifestations in the Oral Cavity

Abstract

Candidiasis is a very common malady in the head neck region. This review will concentrate on intraoral, pharyngeal and perioral manifestations and treatment. A history of the origins associated with candidiasis will be introduced. In addition, oral conditions associated with candidiasis will be mentioned and considered. The various forms of oral and maxillofacial candidiasis will be reviewed to include pseudomembranous, acute, chronic, median rhomboid glossitis, perioral dermatitis, and angular cheilitis. At the end of this review the clinician will be better able to diagnose and especially treat candidal overgrowth of the oral facial region. Of particular interest to the clinician are the various treatment modalities with appropriate considerations for side effects.

http://bit.ly/2G7qMmO

Non-HPV Papillary Lesions of the Oral Mucosa: Clinical and Histopathologic Features of Reactive and Neoplastic Conditions

Abstract

Excluding human papillomavirus (HPV)-driven conditions, oral papillary lesions consist of a variety of reactive and neoplastic conditions and, on occasion, can herald internal malignancy or be part of a syndrome. The objectives of this paper are to review the clinical and histopathological features of the most commonly encountered non-HPV papillary conditions of the oral mucosa. These include normal anatomic structures (retrocuspid papillae, lingual tonsils), reactive lesions (hairy tongue, inflammatory papillary hyperplasia), neoplastic lesions (giant cell fibroma), lesions of unknown pathogenesis (verruciform xanthoma, spongiotic gingival hyperplasia) and others associated with syndromes (for instance Cowden syndrome) or representing paraneoplastic conditions (malignant acanthosis nigricans). Common questions regarding differential diagnosis, management, and diagnostic pitfalls are addressed, stressing the importance of clinico-pathologic correlation and collaboration.

http://bit.ly/2FUqLDk

Lumps and Bumps of the Gingiva: A Pathological Miscellany

Abstract

Lesions of the gingivae are amongst the commonest lesions seen in patients and the vast majority are reactive hyperplasias, related to a number of chronic irritant stimuli. However, there are a number of entities that have a predilection for the gingivae, which are much less common in other parts of the oral cavity. The purpose of this paper is to discuss the clinical and histological differential diagnoses when presented with a lump on the gingivae, including the approach to diagnosis and diagnostic pitfalls.

http://bit.ly/2FWagql

Erythematous and Vascular Oral Mucosal Lesions: A Clinicopathologic Review of Red Entities

Abstract

Erythematous lesions of the oral mucosa are common and can reflect a variety of conditions, ranging from benign reactive or immunologically-mediated disorders to malignant disease. Together with vascular abnormalities, which can vary from reddish to bluish-purple in color, the differential diagnosis for erythematous oral mucosal change is quite diverse. This review focuses on salient clinical features and histopathologic findings of selected conditions which clinically present as red or vascular-like oral mucosal alterations, including oral vascular malformations and neoplasms, pyogenic granuloma, localized juvenile spongiotic gingival hyperplasia, denture stomatitis, benign migratory glossitis (geographic tongue), orofacial granulomatosis, granulomatosis with polyangiitis (Wegener granulomatosis), megaloblastic anemia, and erythroplakia. Recognition of the characteristic clinical features of these conditions, in conjunction with thorough patient history, will allow clinicians to narrow the differential diagnosis and guide appropriate clinical decision making, including the need for tissue biopsy, in order to complete the diagnostic process and initiate optimal patient care.

http://bit.ly/2G7qUmo

Black and Brown Oro-facial Mucocutaneous Neoplasms

Abstract

Black and brown-colored mucocutaneous lesions present a differential diagnostic challenge, with malignant melanoma being the primary clinical concern. The vast majority of pigmented lesions in the head and neck region are the result of benign, reactive factors such as post-inflammatory melanosis. However, it is not uncommon to discover a range of muco-cutaneous black and brown neoplasms in the oro-facial area. The majority of black/brown pigmented neoplasms are melanocytic in origin; these are neoplasms of neural crest derivation. Melanocytic nevi are a diverse group of benign neoplasms that are the result of specific oncogenic mutations. They are common on cutaneous surfaces but can manifest in mucosal sites. Currently, nevi are classified based on clinical and histological criteria. The most common cutaneous and oral mucosal nevus is the acquired melanocytic nevus; nevi do not pose an increased risk for the development of malignant melanoma. Emerging information on specific genetic differences supports the notion of biologically distinct nevi. This article will review the classic clinical and microscopic features of nevi commonly found in the head and neck region, and discuss emerging concepts in nevus pathogenesis and taxonomy. Melanoma is a malignant melanocytic neoplasm and is a result of cumulative genetic deregulation. The etiology of malignant melanoma (MM) is multifactorial and includes underlying genetic susceptibility, UV radiation, skin-type, and race. The majority of MM occurs on cutaneous surfaces and less commonly on mucosal and extra-cutaneous visceral organs. Regardless of location, MM exhibits clinical-pathological features that relate to horizontal or vertical tumor spread. Cutaneous and mucosal MM typically present as asymmetrical, irregularly bordered, large (> 0.5 cm), heterogeneous brown-black lesions with foci of erythema, atrophy or ulceration. As with melanocytic nevi, advances in melanomagenesis research have revealed primary oncogenic BRAF and NRAS mutations associated with cutaneous MM. Unlike their cutaneous counterparts, mucosal melanomas exhibit primary oncogenic alterations in c-KIT and other genes. This article will discuss the role of specific primary oncogenic and secondary/tertiary genetic defects in differential clinical presentation, anatomic distribution, future classification changes, and targeted therapy of melanoma. The clinical and microscopic features of mucosal melanomas and a summary of management guidelines will be discussed. Additionally, this article will cover the salient features of melanocytic neuroectodermal tumor of infancy, a neoplastic entity that can involve the oro-facial region, and the clinical-pathological features of selected, commonly occurring pigmented ectodermally-derived neoplasms that are often part of the clinical differential diagnosis of black–brown pigmented lesions.

http://bit.ly/2G6YR6q

A Guide to Yellow Oral Mucosal Entities: Etiology and Pathology

Abstract

When faced with an uncertain clinical pathosis in the oral cavity, identifying the color of the mucosal lesion helps to narrow down a differential diagnosis. Although less common than red and white lesions, yellow lesions encompass a small group of distinct mucosal pathologic entities. Adipose tissue, lymphoid tissue, and sebaceous glands are naturally occurring yellow constituents of the oral cavity and become apparent with associated developmental or neoplastic lesions. Reactive and inflammatory lesions can create a yellow hue due to purulence, necrosis, and calcification. Some systemic diseases are known to deposit yellow bi-products such as amyloid or bilirubin into the oral mucosa of an affected person, and while not always yellow, unusual entities like verruciform xanthoma and granular cell tumor fall under the umbrella of yellow lesions given their occasional propensity to demonstration the color. This chapter aims to explore the unique group that is yellow lesions presenting in the oral mucosa.

http://bit.ly/2TfsKp2

Black and Brown Oro-facial Mucocutaneous Neoplasms

Abstract

Black and brown-colored mucocutaneous lesions present a differential diagnostic challenge, with malignant melanoma being the primary clinical concern. The vast majority of pigmented lesions in the head and neck region are the result of benign, reactive factors such as post-inflammatory melanosis. However, it is not uncommon to discover a range of muco-cutaneous black and brown neoplasms in the oro-facial area. The majority of black/brown pigmented neoplasms are melanocytic in origin; these are neoplasms of neural crest derivation. Melanocytic nevi are a diverse group of benign neoplasms that are the result of specific oncogenic mutations. They are common on cutaneous surfaces but can manifest in mucosal sites. Currently, nevi are classified based on clinical and histological criteria. The most common cutaneous and oral mucosal nevus is the acquired melanocytic nevus; nevi do not pose an increased risk for the development of malignant melanoma. Emerging information on specific genetic differences supports the notion of biologically distinct nevi. This article will review the classic clinical and microscopic features of nevi commonly found in the head and neck region, and discuss emerging concepts in nevus pathogenesis and taxonomy. Melanoma is a malignant melanocytic neoplasm and is a result of cumulative genetic deregulation. The etiology of malignant melanoma (MM) is multifactorial and includes underlying genetic susceptibility, UV radiation, skin-type, and race. The majority of MM occurs on cutaneous surfaces and less commonly on mucosal and extra-cutaneous visceral organs. Regardless of location, MM exhibits clinical-pathological features that relate to horizontal or vertical tumor spread. Cutaneous and mucosal MM typically present as asymmetrical, irregularly bordered, large (> 0.5 cm), heterogeneous brown-black lesions with foci of erythema, atrophy or ulceration. As with melanocytic nevi, advances in melanomagenesis research have revealed primary oncogenic BRAF and NRAS mutations associated with cutaneous MM. Unlike their cutaneous counterparts, mucosal melanomas exhibit primary oncogenic alterations in c-KIT and other genes. This article will discuss the role of specific primary oncogenic and secondary/tertiary genetic defects in differential clinical presentation, anatomic distribution, future classification changes, and targeted therapy of melanoma. The clinical and microscopic features of mucosal melanomas and a summary of management guidelines will be discussed. Additionally, this article will cover the salient features of melanocytic neuroectodermal tumor of infancy, a neoplastic entity that can involve the oro-facial region, and the clinical-pathological features of selected, commonly occurring pigmented ectodermally-derived neoplasms that are often part of the clinical differential diagnosis of black–brown pigmented lesions.

http://bit.ly/2G6YR6q

HPV-Related Papillary Lesions of the Oral Mucosa: A Review

Abstract

Human papillomaviruses (HPVs) are causative of a group of clinically papillary lesions. The HPV-related lesions of the oral cavity include squamous papilloma, condyloma acuminatum, verruca vulgaris, and multifocal epithelial hyperplasia. Benign entities, such as verruciform xanthoma or giant cell fibroma, as well as malignancies, such as papillary squamous cell carcinoma and verrucous carcinoma, may be considered in the clinical and/or histologic differential diagnoses of these lesions. Mechanisms of infection, epidemiology, clinical presentations, histologic features, and differential diagnoses of the HPV-related oral pathologies are discussed. Current concepts of viral transmission, especially as pertaining to lesions in pediatric patients, and the impacts of HPV vaccination are reviewed.

http://bit.ly/2FYoPtE

Candidiasis: Red and White Manifestations in the Oral Cavity

Abstract

Candidiasis is a very common malady in the head neck region. This review will concentrate on intraoral, pharyngeal and perioral manifestations and treatment. A history of the origins associated with candidiasis will be introduced. In addition, oral conditions associated with candidiasis will be mentioned and considered. The various forms of oral and maxillofacial candidiasis will be reviewed to include pseudomembranous, acute, chronic, median rhomboid glossitis, perioral dermatitis, and angular cheilitis. At the end of this review the clinician will be better able to diagnose and especially treat candidal overgrowth of the oral facial region. Of particular interest to the clinician are the various treatment modalities with appropriate considerations for side effects.

http://bit.ly/2G7qMmO

Non-HPV Papillary Lesions of the Oral Mucosa: Clinical and Histopathologic Features of Reactive and Neoplastic Conditions

Abstract

Excluding human papillomavirus (HPV)-driven conditions, oral papillary lesions consist of a variety of reactive and neoplastic conditions and, on occasion, can herald internal malignancy or be part of a syndrome. The objectives of this paper are to review the clinical and histopathological features of the most commonly encountered non-HPV papillary conditions of the oral mucosa. These include normal anatomic structures (retrocuspid papillae, lingual tonsils), reactive lesions (hairy tongue, inflammatory papillary hyperplasia), neoplastic lesions (giant cell fibroma), lesions of unknown pathogenesis (verruciform xanthoma, spongiotic gingival hyperplasia) and others associated with syndromes (for instance Cowden syndrome) or representing paraneoplastic conditions (malignant acanthosis nigricans). Common questions regarding differential diagnosis, management, and diagnostic pitfalls are addressed, stressing the importance of clinico-pathologic correlation and collaboration.

http://bit.ly/2FUqLDk

Tongue Lumps and Bumps: Histopathological Dilemmas and Clues for Diagnosis

Abstract

Exophytic lesions of the tongue encompass a diverse spectrum of entities. These are most commonly reactive, arising in response to local trauma but can also be neoplastic of epithelial, mesenchymal or miscellaneous origin. In most cases, the microscopic examination is likely to provide a straightforward diagnosis. However, some cases can still raise microscopic diagnostic dilemmas, such as conditions that mimic malignancies, benign tumors with overlapping features and anecdotal lesions. A series of "lumps and bumps" of the tongue are presented together with suggested clues that can assist in reaching a correct diagnosis, emphasizing the importance of the clinico-pathological correlations.

http://bit.ly/2G7qH2u

Lumps and Bumps of the Gingiva: A Pathological Miscellany

Abstract

Lesions of the gingivae are amongst the commonest lesions seen in patients and the vast majority are reactive hyperplasias, related to a number of chronic irritant stimuli. However, there are a number of entities that have a predilection for the gingivae, which are much less common in other parts of the oral cavity. The purpose of this paper is to discuss the clinical and histological differential diagnoses when presented with a lump on the gingivae, including the approach to diagnosis and diagnostic pitfalls.

http://bit.ly/2FWagql

Influence of the Maillard Reaction on the Allergenicity of Food Proteins and the Development of Allergic Inflammation

Abstract

Purpose of Review

The Maillard reaction (MR) is a non-enzymatic reaction between reducing sugars and compounds with free amino groups such as proteins and takes place during thermal processing and storage of foods. This review aims to discuss potential effects of dietary MR products on the pathological mechanisms of allergic diseases.

Recent Findings

Since the MR leads to modification of proteins with various types of glycation structures, the impact of the MR on the immunogenicity and potential allergenicity of food proteins in many allergenic foods has been assessed. In addition, recent studies have suggested that the MR products, in particular "advanced glycation end products (AGEs)," contained in the diet may be involved in the development of chronic inflammation by acting as inflammatory components and affecting the gut microbiome.

Summary

This review found that the biological, immunological, and allergic properties of dietary MR products are diverse due to the complexity of the MR.

http://bit.ly/2B7oCAp

Next-Generation Approaches for the Treatment of Food Allergy

Abstract

Purpose of Review

IgE-mediated food allergies are an increasing health concern, and current management includes food avoidance and use of emergency medications. Effective treatment of food allergy is highly desirable. Next generation approaches for the treatment of food allergy aim to improve both safety and efficacy, potentially including long-term tolerance.

Recent Findings

Oral immunotherapy (OIT) and epicutaneous immunotherapy (EPIT) will likely be integrated into clinical practice as part of food allergy management in the near future. Newer approaches, such as sublingual immunotherapy (SLIT), modified proteins, lysosomal-associated membrane protein DNA (LAMP DNA) vaccines, and the use of immunomodulatory agents, are early in development and depending on results, could also become important treatment options.

Summary

This is a review of novel approaches to the treatment of food allergy that are currently under investigation, including the use of SLIT, modified proteins, probiotics, Chinese herbal supplements, biologic therapies, and DNA vaccines, as well as a summary of the current status of OIT and EPIT.

http://bit.ly/2Tgz53j

Susceptibility of mecillinam in Enterobacterales - results from a prospective in vitro study [Susceptibility]

The activity of mecillinam was assessed in Enterobacterales (n=420) isolated from urines in 2016/2017. Mecillinam susceptibility was 97.4% in E. coli (294/302), 89.7% in Klebsiella spp. (52/58) and 93.3 % in Proteus mirabilis (28/30). Among ESBL producers 95.2% (99/104) were mecillinam susceptible, including two OXA-48-producing K. pneumoniae. In Enterobacter spp. and Citrobacter spp., minimal inhibitory concentration were low (MIC₅₀=0.5 mg/L). In conclusion, the activity of mecillinam was high in Enterobacterales, even among multidrug-resistant isolates.

http://bit.ly/2B4jGfl

In vitro activity of a novel antifungal compound, MYC-053, against clinically significant antifungal-resistant strains of Candida glabrata, Candida auris, Cryptococcus neoformans, and Pneumocystis spp. [Experimental Therapeutics]

An urgent need exists for new antifungal compounds to treat fungal infections in immunocompromised patients. The aim of the current study was to investigate the potency of a novel antifungal compound, MYC-053, against the emerging yeast and yeast-like pathogens Candida glabrata, Candida auris, Cryptococcus neoformans, and Pneumocystis spp. MYC-053 was equally effective against the susceptible control strains, clinical isolates, and resistant strains, with the minimum inhibitory concentrations (MIC) of 0.125–4.0 μg/mL. Notably, unlike other antifungals such as azoles, polyenes and echinocandins, MYC-053 was effective against Pneumocystis isolates, therefore being the only synthetic antifungal that may potentially be used against Pneumocistis spp., Candida spp., and Cryptococcus spp.

MYC-053 was highly effective against preformed 48-h-old C. glabrata and C. neoformans biofilms, with the minimal biofilm eradication concentrations equal to 1–4 times MIC. Together, these data indicated that MYC-053 may be developed into a promising antifungal agent for the treatment and prevention of invasive fungal infections caused by yeasts and yeast-like fungi.

http://bit.ly/2TkEsP8

Y229W substitution in NDM-1/L209F variant restores the hydrolytic activity of the enzyme towards penicillins, cephalosporins and carbapenems: kinetic profile and molecular dynamic studies [Mechanisms of Resistance]

NDM-1 enzyme is the most common metallo-β-lactamase identified in many Gram-negative bacteria causing severe nosocomial infections. The aim of this study was to focus the attention on non-active site residues, L209 and Y229, of NDM-1 and to investigate their role in the catalytic mechanism. Specifically, the effect of Y229W substitution in L209F variant was evaluated by antimicrobial susceptibility testing, kinetic and molecular dynamic (MD) studies. The Y229W single mutant and L209F/Y229W double mutant were generated by site-directed mutagenesis. The K_m, k_cat and k_cat/K_m kinetic constants, calculated for the two mutants, were compared with those of NDM-1 and L209F variants. Compared to L209F single mutant, L209F/Y229W mutant showed a remarkable increase of k_cat values of 100-, 240-, 250- and 420-fold for imipenem, meropenem, benzylpenicillin and cefepime, respectively. In L209F/Y229W enzyme we observed a remarkable increase of k_cat/K_m of 370-, 140- and 80-fold for cefepime, meropenem and cefazolin, respectively. The same behavior was stated by antimicrobial susceptibility test. MD simulations were carried out on both L209F and L209F/Y229W enzymes complexed with benzylpenicillin focusing the attention on the overall mechanical features and on the differences between the two systems. With respect to L209F variant, the L209F/Y229W double mutant showed a mechanical stabilization of Loop 10 and N-terminal region but a destabilization of C-terminal and 149-154 regions. The epistatic effect of Y229W mutation jointly with stabilization of Loop 10 lead to a better catalytic efficiency of β-lactams. NDM numbering is used in order to facilitate the comparison with other NDM-1 studies.

http://bit.ly/2BbaMwL

Predicting Antibiotic Resistance in Gram-negative Bacilli from Resistance Genes [Mechanisms of Resistance]

We developed a rapid high throughput polymerase chain reaction (PCR) test and evaluated highly antibiotic-resistant clinical isolates of Escherichia coli (n=2919), Klebsiella pneumoniae (1974), Proteus mirabilis (1150) and Pseudomonas aeruginosa (1484) for several antibiotic resistance genes for comparison with phenotypic resistance across penicillins, cephalosporins, carbapenems, aminoglycosides, trimethoprim-sulfamethoxazole, fluoroquinolones and macrolides. The isolates originated from hospitals in North America (34%), Europe (23%), Asia (13%), South America (12%), Africa (7%), Oceania (1%) or unknown (9%). We developed statistical methods to predict phenotypic resistance from resistance genes for 49 antibiotic/organism combinations, including gentamicin, tobramycin, ciprofloxacin, levofloxacin, trimethoprim/sulfamethoxazole, ertapenem, imipenem, cefazolin, cefepime, cefotaxime, ceftazidime, ceftriaxone, ampicillin and aztreonam. Average positive predictive values for genotypic prediction of phenotypic resistance was E. coli (91%), K. pneumoniae (93%), P. mirabilis (87%) and P. aeruginosa (92%) across the various antibiotics for this highly resistant cohort of bacterial isolates.

http://bit.ly/2TfowxG

Updated Prevalence of mcr-like Genes among Escherichia coli and Klebsiella pneumoniae in SENTRY Program and Characterization of mcr-1.11 Variant [Letters]

Increased prevalence of infections caused by Gram-negative pathogens that are multidrug resistant has prompted the reconsideration of polymyxins as therapeutic options....

http://bit.ly/2BbSk7f

Src Family Kinase Inhibitors Block Translation of Alphavirus Subgenomic mRNAs [Antiviral Agents]

Alphaviruses are arthropod-transmitted RNA viruses that can cause arthralgia, myalgia, and encephalitis in humans. Since the role of cellular kinases in alphavirus replication is unknown, we profiled kinetic changes in host kinase abundance and phosphorylation following chikungunya virus (CHIKV) infection of fibroblasts. Based upon the results of this study, we treated CHIKV infected cells with kinase inhibitors targeting the SFK-PI3K-AKT-mTORC signaling pathways. Treatment of cells with Src Family Kinase (SFK) inhibitors blocked the replication of CHIKV, as well as multiple other alphaviruses including Mayaro virus, o'nyong-nyong virus, Ross River virus, and Venezuelan equine encephalitis virus. Dissecting the effect of SFK inhibition on alphavirus replication, we found that viral structural protein levels were significantly reduced, but synthesis of viral genomic and subgenomic RNAs was unaffected. By measuring the association of viral RNA with polyribosomes we found that the SFK inhibitor dasatinib blocks alphavirus subgenomic RNA translation. Our results demonstrate a role for SFK signaling in alphavirus subgenomic RNA translation and replication. Targeting host factors involved in alphavirus replication represents an innovative, perhaps paradigm-shifting strategy for exploring replication of CHIKV and other alphaviruses, while promoting antiviral therapeutic development.

http://bit.ly/2Tg4vGZ

Large-Scale Identification of AbaR-Type Genomic Islands in Acinetobacter baumannii Reveals Diverse Insertion Sites and Clonal Lineage-Specific Antimicrobial Resistance Gene Profiles [Mechanisms of Resistance]

AbaR-type genomic islands (AbaRs) are important elements responsible for antimicrobial resistance in Acinetobacter baumannii. This study performed a large-scale identification of AbaRs to understand their distribution and compositions of antimicrobial resistance genes. We identified 2.89-kb left-end and 1.87-kb right-end conserved sequences (CSs) and developed a bioinformatics approach to identify AbaRs using the CSs as signatures in 3148 publicly available genomes. AbaRs were prevalent in A. baumannii, as being found in 2091 genomes. They were sparse in other Acinetobacter species and confined only to this genus. Results from 111 complete genomes showed that over 85% AbaRs resided on chromosomes. The external flanks adjacent to the inverted repeats available in all identified CSs were mapped to an AbaR-free chromosome or search in the NCBI database for empty loci to define insertion sites. Surprisingly, 84 insertion sites were revealed with diverse origins, including 51 scattered on the chromosome, 20 plasmid-borne, 12 locating on prophages, transposons, ISAba1, complex AbaRs and genomic islands of other type, and one uncharacterised, and some were strongly associated with clonal lineages. Finally, we found 994 antimicrobial resistance genes covering 28 unique ones from 70.9% (299/422) intact AbaRs currently available. The resistance gene profiles displayed an apparent clonal lineage-specific pattern, highlighting the distinct features of AbaRs in global clones (GCs) 1 and 2. The tet(B) was highly specific to the AbaRs in GC2. In conclusion, AbaRs have diverse insertion sites on the chromosome and mobile genetic elements and display distinct antimicrobial resistance gene profiles in different clonal lineages.

http://bit.ly/2B7MyDK

Population pharmacokinetics with Monte Carlo simulations of gentamicin in an adult severely ill sub-Saharan African patient population [Pharmacology]

In sub-Saharan Africa (SSA), gentamicin is commonly used for severe infections in non-ICU settings, but pharmacokinetic and pharmacodynamic data for this specific population are lacking. We performed a population pharmacokinetic study in an adult Mozambican non-ICU hospital population (n=48) treated with gentamicin and developed a pharmacokinetic model using non-linear mixed effect modeling. Simulations showed that non-ICU SSA patient populations may be at substantial risk for underexposure to gentamicin during routine once-daily dosing.

http://bit.ly/2Tg4t1P

A Combination Antibiogram Evaluation for Pseudomonas aeruginosa in Respiratory and Blood Sources from ICU and Non-ICU Settings in US Hospitals [Susceptibility]

Background: Pseudomonas aeruginosa (PsA) is an important pathogen associated with significant morbidity and mortality. US guidelines for hospital-acquired and ventilator-associated pneumonia recommend the use of two antipseudomonal drugs for high-risk patients to ensure ≥95% of patients receive active empiric therapy. We evaluated the utility of combination antibiograms in identifying optimal PsA drug regimens.

Methods: We conducted a retrospective cross-sectional analysis of antimicrobial susceptibility of all non-duplicate PsA blood and respiratory isolates collected between October 1, 2016 and September 30, 2017 from 304 US hospitals in the BD Insights Research Database. Combination antibiograms were used to determine in vitro antimicrobial susceptibility rates for potential PsA combination regimens consisting of a backbone antibiotic (extended-spectrum cephalosporin, carbapenem, or piperacillin/tazobactam) plus an aminoglycoside or fluoroquinolone.

Results: Single agent susceptibility rates for the 11,701 non-duplicate PsA isolates ranged from 72.7% for fluoroquinolones to 85.0% for piperacillin/tazobactam. Susceptibility rates were higher for blood versus respiratory isolates (P < 0.05). Antibiotic combinations resulted in increased susceptibility rates, but did not achieve the goal of 95% antibiotic coverage. Adding an aminoglycoside resulted in higher susceptibility rates than adding a fluoroquinolone; piperacillin/tazobactam plus an aminoglycoside had the highest susceptibility rate (93.3%). Intensive care unit (ICU) isolates generally had lower susceptibility rates than non-ICU isolates.

Conclusions: Commonly-used antipseudomonal drugs, either alone or in combination, do not achieve 95% coverage against US hospital PsA isolates, suggesting that new drugs are needed to attain this goal. Local institutional use of combination antibiograms has the potential to optimize empiric therapy of difficult-to-treat pathogens.

http://bit.ly/2B9tsND

Emergence of Neisseria gonorrhoeae Strains Harboring a Novel Combination of Azithromycin-attenuator Mutations. [Susceptibility]

The nimbleness of N. gonorrhoeae to evade the effect of antibiotics has perpetuated the fight against antibiotic-resistant gonorrhea for more than 80 years. The ability to develop resistance to antibiotics is attributable to its indiscriminate nature in accepting and integrating exogenous DNA into its genome. Here, we provide data demonstrating a novel combination of the 23S rRNA A2059G mutation with a mosaic-mtr locus haplotype in fourteen N. gonorrhoeae isolates with high-level azithromycin MICs (≥ 256 μg/ml), a combination that may confer more fitness than previously identified isolates with high-level azithromycin resistance. To our knowledge, this is the first description of N. gonorrhoeae strains harboring this novel combination of resistance determinants. These strains were isolated at two independent jurisdictions participating in the Gonococcal Isolate Surveillance Project (GISP) and in the Strengthening the U.S. Response to Resistant Gonorrhea (SURRG) project. The data suggest that N. gonorrhoeae's genome continues to shuffle its genetic material. These findings further illuminate the genomic plasticity of N. gonorrhoeae, which allows this pathogen to develop mutations to escape the inhibitory effects of antibiotics.

http://bit.ly/2Tg4nHv

The anthelmintic drug niclosamide synergizes with colistin and reverses colistin resistance in Gram-negative bacilli. [Susceptibility]

There is an urgent need for new therapies to overcome antimicrobial resistance especially in Gram-negative bacilli (GNB). Repurposing old FDA-approved drugs as complimentary agents to existing antibiotics in a synergistic combination presents an attractive strategy. Herein, we demonstrate that the anthelmintic drug niclosamide selectively synergized with the lipopeptide antibiotic colistin against colistin-susceptible but more importantly against colistin-resistant GNB, including clinical isolates that harbor the mcr-1 gene. Breakpoints for colistin susceptibility in resistant Gram-negative bacilli were reached in the presence of 1 μg/mL (3 μM) niclosamide. Reversal of colistin-resistance was also observed in combinations of niclosamide and polymyxin B. Enhanced bacterial killing was evident for the combination, in comparison to colistin monotherapy, against resistant Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, Escherichia coli and Enterobacter cloacae. Accumulating evidence in the literature along with our results strongly suggest the potential for the combination of niclosamide and colistin to treat colistin-resistant Gram-negative bacillary infections. Our finding is significant since colistin is an antibiotic of last resort for multidrug-resistant Gram-negative bacterial infections that are non-responsive to conventional treatments. With the recent global dissemination of plasmid-encoded colistin resistance, addition of niclosamide to colistin therapy may hold the key to overcome colistin resistance.

http://bit.ly/2B8gijD

A Small Molecule Inhibitor of Trans-Translation Synergistically Interacts with Cathelicidin Antimicrobial Peptides to Impair Survival of Staphylococcus aureus [Experimental Therapeutics]

Staphylococcus aureus is a leading cause of infection in the US and, due to the rapid development of resistance, new antibiotics are constantly needed. Trans-translation is a particularly promising antibiotic target because it is conserved in many bacterial species, is critical to bacterial survival, and is unique among prokaryotes. We have investigated the potential of KKL-40, a small molecule inhibitor of trans-translation, and find that it inhibits both methicillin-susceptible and methicillin-resistant strains of S. aureus. KKL-40 is also effective against Gram-positive pathogens including a vancomycin-resistant strain of Enterococcus faecalis, Bacillus subtilis and Streptococcus pyogenes, although its performance with Gram-negatives is mixed. KKL-40 synergistically interacts with the human antimicrobial peptide LL-37, a member of the cathelicidin family, to inhibit S. aureus but not other antibiotics tested including daptomycin, kanamycin or erythromycin. KKL-40 is not cytotoxic to HeLa cells at concentrations that are 100-fold greater than the effective MIC. We also find that S. aureus develops minimal resistance to KKL-40 even after multi-day passage in sub-lethal concentrations. Therefore, trans-translation inhibitors could be a particularly promising drug target against S. aureus, not only because of their ability to inhibit bacterial growth, but also because of their potential to simultaneously render S. aureus more susceptible to host antimicrobial peptides.

http://bit.ly/2TkErL4

Comment on: ‘Treatment of psoriasis with ustekinumab in a patient with HIV‐related Kaposi sarcoma’

Abstract

We read with great interest the recent article by Wang et al.¹ reporting on a psoriatic patient co‐affected by HIV‐related Kaposi's sarcoma (KS), whose poorly controlled psoriasis was successfully treated with ustekinumab, a fully monoclonal antibody that targets the common p40 subunit shared by interleukins (IL)‐12 and IL‐23. Interestingly, despite the evidences supporting the role of IL‐12 in inhibiting tumorigenesis,² the authors reported no KS progression after a 16‐month follow‐up.

This article is protected by copyright. All rights reserved.

http://bit.ly/2TltEjC

Vulvar squamous cell carcinoma: a clinico‐dermoscopic correlation

Abstract

Squamous cell carcinoma (SCC) is the most common malignant vulvar tumor.1 It primarily affects post‐menopausal women; its precursor lesions are vulvar intraepithelial neoplasia (VIN), in particular the "differentiated" subtype, and/or human papillomavirus (HPV) infection.1 The final diagnosis of vulvar SCC is made by histopathology, which is similar to that of SCC affecting other body areas, distinguishing between well differentiated forms and poorly differentiated tumors.

This article is protected by copyright. All rights reserved.

http://bit.ly/2BaxOEa

Liquid chromatography–mass spectrometry is effective for Analysis of Ergosterol in Fungus Infected Nails

Abstract

Background

The identification of onychomycosis is mainly based on clinical diagnosis with auxiliary diagnostic methods such as KOH microscopy, PAS staining, or mold culture. However, they are limited by the sensitivity and specificity of each type of method. Therefore, our aim is to develop a new test method using the common end product – ergosterol – test to see if it can be used as a new diagnostic tool.

Materials and Methods

We collected consecutive data from 20 subjects with nail problems. After the clinical diagnosis, the subjects received a KOH microscopy test and the extraction of specimens for the mass spectrometer test to check for the presence of ergosterol.

Results

Among the 20 cases collected, seven came out positive by the mass spectrometry test. Four of them were suspected as onychomycosis, whereas one of the remaining three subjects was presumed to be dry nail and the other two as onycholysis. It is obvious that it is easier for the mass spectrometer test to find composites.

Conversely, among the five clinically diagnosed onychomycosis, four came out positive by mass spectrometer whereas the other one was detected negative by KOH and mass spectrometer. Three other subjects were positive with KOH test with mass spectrometer test also resulting to be positive.

Conclusion

The detection of the presence of ergosterol by a mass spectrometer is one of the good tools for confirming onychomycosis. However, there is a need to conduct studies to verify the sensitivity and specificity of the mass spectrometer method.

This article is protected by copyright. All rights reserved.

http://bit.ly/2Tird1p

Eccrine Porocarcinoma in a patient with Schöpf–Schulz–Passarge syndrome

Abstract

Histological analysis of the lesion proved to be challenging. An initial punch biopsy showed an ulcerated tumour comprised of islands of monomorphic cells with duct formation pushed deep into the dermis, and a lace‐like pattern of infiltration. At this point a diagnosis of eccrine porocarcinoma was favoured over poroma due to the presence of desmoplastic response and focal infiltrative growth pattern.

This article is protected by copyright. All rights reserved.

http://bit.ly/2B8bmLD

A retrospective review of twelve patients with trichotillomania treated in a psychodermatology service

Summary

Trichotillomania is a condition characterised by the pulling of hair from anywhere on the body and is classified as an obsessive‐compulsive and related disorder. Patients with hair disorders are commonly referred to psychodermatology services, and can represent a management challenge. Few publications exist that report outcomes for patients with trichotillomania in real clinical practice. We report twelve such patients seen within our own psychodermatology service, who were managed using a variety of treatment strategies. The rate of defaulting of appointments was high, but improvements were seen in patients engaging with services.

This article is protected by copyright. All rights reserved.

http://bit.ly/2Tpc8vb

Lower limb cellulitis: low diagnostic accuracy and underdiagnosis of risk factors

Abstract

Accurate diagnosis and recognition of predisposing factors has been shown to be challenging in lower limb cellulitis. Assessment of 1746 consecutive cellulitis patients presenting to a UK university hospital showed increasing overdiagnosis with only 31.9% of referred patients with confirmed lower‐limb cellulitis between 2015‐2018. Recognition of at least one predisposing factor increased from 61% to 89% following introduction of more specific screening questions. This identified a need for better primary care dermatology education and the benefit of a proforma with specific screening questions for reversible predisposing factors for lower limb cellulitis.

This article is protected by copyright. All rights reserved.

http://bit.ly/2Bal1Bq

Effects of Musical Training and Hearing Loss on Fundamental Frequency Discrimination and Temporal Fine Structure Processing: Psychophysics and Modeling

Abstract

Several studies have shown that musical training leads to improved fundamental frequency (F₀) discrimination for young listeners with normal hearing (NH). It is unclear whether a comparable effect of musical training occurs for listeners whose sensory encoding of F₀ is degraded. To address this question, the effect of musical training was investigated for three groups of listeners (young NH, older NH, and older listeners with hearing impairment, HI). In a first experiment, F₀ discrimination was investigated using complex tones that differed in harmonic content and phase configuration (sine, positive, or negative Schroeder). Musical training was associated with significantly better F₀ discrimination of complex tones containing low-numbered harmonics for all groups of listeners. Part of this effect was caused by the fact that musicians were more robust than non-musicians to harmonic roving. Despite the benefit relative to their non-musicians counterparts, the older musicians, with or without HI, performed worse than the young musicians. In a second experiment, binaural sensitivity to temporal fine structure (TFS) cues was assessed for the same listeners by estimating the highest frequency at which an interaural phase difference was perceived. Performance was better for musicians for all groups of listeners and the use of TFS cues was degraded for the two older groups of listeners. These findings suggest that musical training is associated with an enhancement of both TFS cues encoding and F₀ discrimination in young and older listeners with or without HI, although the musicians' benefit decreased with increasing hearing loss. Additionally, models of the auditory periphery and midbrain were used to examine the effect of HI on F₀ encoding. The model predictions reflected the worsening in F₀ discrimination with increasing HI and accounted for up to 80 % of the variance in the data.

http://bit.ly/2SdY0au

“To Biologic or Not to Biologic?: The Question of Cost-Effectiveness”

As of 2018, the FDA had approved five biologics for the treatment of asthma – omalizumab, mepolizumab, reslizumab, benralizumab, and dupilumab. All five of these biologics are designated for the treatment of severe asthma in patients with a TH2-driven phenotype, either allergic or eosinophilic. In clinical trials, biologics have demonstrated efficacy to decrease the frequency of asthma exacerbations, unplanned health utilization including ED visits and hospitalizations, and chronic oral steroid use in severe asthmatic patients1.

http://bit.ly/2sRvUnp

Economic burden of food allergy- A systematic review

Food allergy (FA) is a life-threatening condition that is a growing health concern worldwide. Currently in the United States, 8% of children have a parent-reported FA.1 Much of the epidemiological work on FA has focused primarily on children; however, recent estimates have found that 10.8% of adults in the US have a self-reported FA.2 Furthermore, numerous studies have estimated the prevalence of FA in children from countries across Europe including France (6.7%),3 Greece (5.2%),4 and Sweden (6.8%).

http://bit.ly/2MDDFpX

Effects of Musical Training and Hearing Loss on Fundamental Frequency Discrimination and Temporal Fine Structure Processing: Psychophysics and Modeling

Abstract

Several studies have shown that musical training leads to improved fundamental frequency (F₀) discrimination for young listeners with normal hearing (NH). It is unclear whether a comparable effect of musical training occurs for listeners whose sensory encoding of F₀ is degraded. To address this question, the effect of musical training was investigated for three groups of listeners (young NH, older NH, and older listeners with hearing impairment, HI). In a first experiment, F₀ discrimination was investigated using complex tones that differed in harmonic content and phase configuration (sine, positive, or negative Schroeder). Musical training was associated with significantly better F₀ discrimination of complex tones containing low-numbered harmonics for all groups of listeners. Part of this effect was caused by the fact that musicians were more robust than non-musicians to harmonic roving. Despite the benefit relative to their non-musicians counterparts, the older musicians, with or without HI, performed worse than the young musicians. In a second experiment, binaural sensitivity to temporal fine structure (TFS) cues was assessed for the same listeners by estimating the highest frequency at which an interaural phase difference was perceived. Performance was better for musicians for all groups of listeners and the use of TFS cues was degraded for the two older groups of listeners. These findings suggest that musical training is associated with an enhancement of both TFS cues encoding and F₀ discrimination in young and older listeners with or without HI, although the musicians' benefit decreased with increasing hearing loss. Additionally, models of the auditory periphery and midbrain were used to examine the effect of HI on F₀ encoding. The model predictions reflected the worsening in F₀ discrimination with increasing HI and accounted for up to 80 % of the variance in the data.

http://bit.ly/2SdY0au

Telementoring and Smart-Phone-Based Answering Systems to Optimize Dermatology Resident Dermoscopy Education

http://bit.ly/2HzOoD6

Predictors of time to relapse following ustekinumab withdrawal in patients with psoriasis who had responded to therapy: An eight-year multicenter study

1. The vast majority of patients with psoriasis flared after stopping ustekinumab treatment. Treatment response, patient characteristics and use of immunosuppressants after cessation of ustekinumab were predictors of time to relapse while off ustekinumab.2. Given high rates of psoriasis relapse, withdrawal of ustekinumab cannot be recommended.

http://bit.ly/2S7vPtZ

“A Reliability Study Using Network-Oriented Research Assistant (NORA®) to Evaluate the Use of Digital Photographs in the Assessment of Atopic Dermatitis”

http://bit.ly/2HyXq37

Patient Satisfaction with the Veteran’s Administration Teledermatology Service

This study adds to the limited fund of knowledge regarding patient attitudes towards and satisfaction with teledermatology services. Patients who struggle with access to advanced dermatologic care should be encouraged to consider teledermatology, as they are highly satisfied across multiple consult outcomes.

http://bit.ly/2S7HKYI

Role of imaging in low grade cutaneous B-cell lymphoma presenting in the skin

•Whole body imaging is the current standard of care as part of staging work-up for all patients presenting with skin lesion(s) of B-cell lymphomas, however the incidence of extracutaneous involvement in indolent cutaneous B-cell lymphoma is unknown. Imaging is effective in identifying the small subset of patients with systemic involvement at staging. After negative initial staging, primary cutaneous marginal zone lymphoma patients may be followed clinically without routine imaging.

http://bit.ly/2HzkPBh

Risk Factors for Keratinocyte Carcinoma Skin Cancer In Nonwhite Individuals: A Retrospective Analysis

The presence of a single skin cancer lesion in a nonwhite individual may be associated with greater morbidity and mortality than in a White patient. Emphasize skin examination and increased vigilance of sun-protected areas in nonwhite patients, particularly the anogenital area, and counsel all patients on smoking cessation.

http://bit.ly/2S7vvvh

Patient-Reported Outcomes are Important Elements of Psoriasis Treatment Decision Making: A Discrete Choice Experiment Survey of Dermatologists in the United States

•Physician-evaluated measures of psoriasis severity are the primary assessments in psoriasis trials; however, U.S. dermatologists also consider patient-reported outcome (PRO) data when selecting a biologic for moderate-to-severe psoriasis patients PRO evaluations should be integrated into psoriasis clinical trials to obtain the information needed to facilitate treatment decision making

http://bit.ly/2HBhKRj

Treatment of Morphea With Hydroxychloroquine: A Retrospective Review of 84 Patients at Mayo Clinic, 1996-2013

Data are sparse on the efficacy of hydroxychloroquine as therapy for morphea. Of our 84 patients, 81% had a complete response or a partial response greater than 50% to hydroxychloroquine. Hydroxychloroquine should be considered a treatment option for morphea.

http://bit.ly/2SgbWRi

Fractionated de-volumizing Keloid tissue - The ‘pop’ method- A novel technique to facilitate administration of intralesional corticosteroid in difficult keloids

http://bit.ly/2HD5i3E

Treatment and survival of Merkel cell carcinoma since 1993: a population-based cohort study in the Netherlands

•Merkel cell carcinoma (MCC) is a potentially lethal skin-cancer with a rapidly increasing incidence in the Netherlands. The 5-year survival of 63% did not improve over time and is worse for males, elderly and advanced disease. Our results emphasise need for implementation of new therapies and research in this field.

http://bit.ly/2S7T1IB

Age as key factor for pattern, timing and extent of distant metastasis in patients with cutaneous melanoma. A study of the German Central Malignant Melanoma Registry

•Older age correlates with better response to immunotherapy in stage IV melanoma patients but the impact of aging on distant metastasis is unclear. This study found an inverse relationship between age at diagnosis and the number of metastatic sites; these findings may have implications for optimizing outcomes of melanoma patients.

http://bit.ly/2HCW6MN

Corrigendum to 'Injection technique in neurotoxins and fillers: Indications, products, and outcomes' [J Am Acad Dermatol 79 (2018) 423–435]

http://bit.ly/2S7vuHJ

Factors associated with suicidal ideation risk in head and neck cancer: A longitudinal study

Objectives/Hypothesis

The risk factors associated with suicidal ideation among patients with head and neck cancer (HNC) have rarely been investigated. Thus, this study proposed an effective screening model to facilitate the identification of patients with HNC who are at risk of committing suicide.

Study Design

Retrospective longitudinal study.

Methods

We recruited 286 inpatients with HNC who were referred to the psychiatry department for an emotional distress assessment during cancer treatment. Sociodemographic and clinical factors, as well as Distress Thermometer (DT) scoring, were gathered and analyzed using multivariate logistic regression.

Results

Among the patients, 27 (9.4%) were recognized as having suicidal ideation. A logistic regression analysis revealed five significant indicators associated with suicidal ideation, namely depression (odds ratio [OR]: 42.83), dysphoria (OR: 8.06), hypopharyngeal cancer (OR: 4.61), cancer history (OR: 4.53), and average DT scores (OR: 1.84). Based on the receiver operating characteristic and logistic regression, the model can predict suicidal ideation with 93.4% accuracy (area under the curve value).

Conclusions

Our findings provide strong evidence that patients with depression, hypopharyngeal cancer, higher DT scores, and previous cancer history can be quickly screened for suicidal ideation, which may help to prevent suicide events in patients with HNC.

Level of Evidence

3b Laryngoscope, 2019

http://bit.ly/2TgGQ9u

EMS quality improvement through clinical specialty teams

Harness a passion for care to identify improvement opportunities in clinical specialty areas and propose change

http://bit.ly/2B5P1ys

A case of dermatomyositis with the anti‐signal recognition particle antibody that was successfully treated with prednisolone and intravenous immunoglobulin therapy

http://bit.ly/2B6kj8w

Development of a standardized evaluation of endobuccal adverse events induced by repeated tongue protrusion with both a dedicated questionnaire and an endobuccal examination

Abstract

Introduction

A new approach to treat obstructive sleep apnea (OSA) is upper airway stimulation therapy (UAS). Electrical pulses applied to the hypoglossal nerve induce tongue protrusion, increase airway patency and decrease the frequency of apneic and hypopneic events. Thus, the main objective of this study was to design a standardized evaluation of endobuccal adverse events induced by repeated tongue protrusion with both a dedicated questionnaire and an endobuccal examination.

Method

This study has designed the Tongue Adverse Event and Satisfaction Questionnaire (TAESQ) and an endobuccal examinations divided into an endobuccal lesion examination (ELE) and an endobuccal risk factor examination (ERFE). Evaluations were conducted at month 6 post-implantation.

Results

The study population after implantation of UAS device consisted of ten Caucasian males with a mean age of 51.9 ± 11.8 years, and a mean BMI of 28.6 ± 3.3. The AHI of the ten participants ranged from 46.7 ± 12.2/h at baseline to 14.5 ± 8.9/h with the Inspire therapy at the 6-month follow-up. The TAESQ revealed pain (30%), followed by less tongue sensitivity (20%) and tongue weakness (10%). The ELE did not reveal any lesions. The ERFE revealed that some participants had tissue and dental risk factors but not associated to more adverse events.

Conclusion

The TAESQ, ELE and ERFE have been designed and studied on a small number of participants. These evaluations could systematically be included in the care pathway of patients treated by UAS to better investigate tongue discomfort and tongue lesion for patients treated with this technology.

http://bit.ly/2GbmdYT

Gender, prick test size and rAra h 2 sIgE level may predict the eliciting dose in patients with peanut allergy: evidence from the Mirabel survey

Abstract

Background

Peanut allergy management is based on active avoidance and access to emergency treatment including self‐injectable adrenaline. Knowing the dose at which a patient is likely to react is crucial for risk assessment and could significantly improve management by integrating a personalized approach.

Objective

To develop a threshold dose distribution curve model from routinely collected data.

Methods

The MIRABEL survey is an observational study of 785 patients with peanut allergy/sensitization conducted in France, Belgium and Luxemburg. The current analysis included the 238 participants for whom medical and oral food challenge data were available. Several statistical models (Kaplan‐Meier, Cox model, Weibull and Lognormal with predictive factors, basic Weibull and Lognormal) were compared to select the best model and predictive factor combination associated with the threshold doses. Inferences were made with a Bayesian approach.

Results

Patients were mainly children (mean age: 9 years [IQR: 6‐11]; 87% < 16 years) and males (62%). Median Ara h2 s IgE was of 8kUA/L [IQR: 1‐55] and median skin prick test size of 10 mm [IQR: 7‐13]. OFC was positive in 204 patients (86%). The median threshold dose was of 67 mg of peanut protein [IQR: 16‐244]. The dose at which 1% of the patients are likely to react with objective symptoms was 0.26 [0.03; 2.24] mg of peanut protein. Gender, size of the skin prick test (SPT) and Ara h 2 specific IgE level had a significant impact on the threshold dose distribution curve. The Cox model was the most effective to predict threshold doses with this combination of factors. Girls react to lower doses than boys with a beta coefficient associated to the risk and a 95% credible interval of 0.44 [0.04; 0.77]. The higher the size of the SPT and the Ara h 2 specific IgE level are, the higher the risk of reacting to a small amount of peanut, with beta coefficients associated to the risk and 95% credible intervals of 0.05 [0.02; 0.08] and 0.01 [0.01; 0.02] respectively.

Conclusion and clinical relevance

according to the model, routinely collected data could be used to estimate the threshold dose. The consequences could be the identification of high‐risk patients who are susceptible to react to small amounts of peanut and a personalized management of peanut allergy integrating the risk of allergic reaction. Limitations of this study are that assessors of OFC outcome were aware of SPT and Arah2 results, and a further validation study is required to confirm the predictive value of these parameters.

This article is protected by copyright. All rights reserved.

http://bit.ly/2BaDMEO

Behandlungsstrategien beim Oropharynxkarzinom

Abstract

Hintergrund

Das Oropharynxkarzinom (OPSCC) stellt aufgrund seiner weltweiten Inzidenzzunahme und der Assoziation mit dem humanen Papillomavirus HPV-16, aber auch chronischem Tabak‑/Alkoholkonsum eine genetisch heterogene Tumorgruppe mit hoher prognostischer Diversität dar.

Ziel

Die Übersichtsarbeit versucht, die aktuelle Sicht der Therapie und Prävention des OPSCC in Hinblick auf die Assoziation mit HPV16 darzustellen.

Material und Methoden

Die Übersicht erfolgt auf der Basis der aktuellen relevanten Literatur sowie der derzeit laufenden Studien.

Ergebnisse und Diskussion

Das OPSCC stellt sich als sehr komplexe, genetisch heterogene und daher detailliert anzusehende Gruppe von Kopf-Hals-Tumoren dar. Die derzeit widersprüchliche Studienlage, die auf dem Boden retrospektiver Daten aktuelle TNM-Klassifikation („8th Edition") und die abzuwartenden prospektiven Daten zur Therapiedeintensivierung ermahnen aktuell eher zu einer konservativen Therapiebetrachtung. Durch die aktuellen Impfempfehlungen ist jetzt auch die HPV-Impfung für Jungen analog zu den Mädchen in Deutschland zugelassen.

http://bit.ly/2G7MdE7

Humane Papillomaviren und das Oropharynxkarzinom

Zusammenfassung

Hintergrund

Das humane Papillomavirus (HPV) gehört zur Familie der Papillomaviren. Basierend auf dem karzinogenen Potenzial der Viren erfolgt die Einteilung in Niedrig- und Hochrisikotypen. Niedrigrisikotypen sind verantwortlich für genitale Papillome und die rekurrierende respiratorische Papillomatose, während HPV-Hochrisikotypen weltweit 5 % der Karzinome induzieren. HPV gilt als sexuell übertragbare Erkrankung und ist, neben der Entstehung anogenitaler Karzinome, im Kopf-Hals-Bereich für die Pathogenese des HPV-assoziierten Oropharynxkarzinoms (OPSCC) verantwortlich.

Methoden

Diese Arbeit basiert auf einer selektiven Literaturrecherche in der Datenbank PubMed zum Thema HPV-assoziierte OPSCC.

Ergebnisse

Die Inzidenz dieser vorrangig in der Tonsille sowie im Zugengrund lokalisierten HPV-assoziierten Kopf-Hals-Karzinome steigt. Aufgrund der virusgetriebenen Karzinogenese unterscheiden sich HPV-assoziierte OPSCC hinsichtlich genetischer und molekularbiologischer Aspekte von den noxenassoziierten OPSCC und weisen im Vergleich eine signifikant verbesserte Prognose auf. Der Nachweis einer HPV-Assoziation erfolgt u. a. über den immunhistochemischen Nachweis einer Überexpression des Surrogatmarkers p16, welcher seit 2017 in der 8. Auflage der TNM-Klassifikation maligner Tumoren berücksichtigt wird. Bisher wird bei der Wahl der Therapie nicht aufgrund des HPV-Status unterschieden, welches in beiden Entitäten zu einer hohen Nebenwirkungsrate führt.

Schlussfolgerung

Um zukünftig eine Therapiedeeskalation bestimmter Patientengruppen zu ermöglichen, wurden prognostische Modelle zur Risikostratifizierung entwickelt. Zur Überwachung des Krankheitsverlaufs sowie der frühzeitigen Detektion eines Therapieversagens werden aktuell Screeningmethoden wie die Flüssigbiopsie auf ihre Validität geprüft. Die HPV-Impfung, welche der primären Prophylaxe einer Tumorentstehung dient, wird für Mädchen sowie seit kurzem auch für Jungen im Alter von 9 bis 14 Jahren von der Ständigen Impfkommission (STIKO) empfohlen.

http://bit.ly/2FTii3l

Teaching communication skills to OTL-HNS residents: multisource feedback and simulated scenarios

Effective communication has been linked to a reduction in adverse events and improved patient compliance. Currently in Otolaryngology – Head and Neck Surgery (OTL-HNS) residency programs, there is limited expl...

http://bit.ly/2HyDg9m

Skeletal open bite with amelogenesis imperfecta treated with compression osteogenesis: a case report

Abstract

Background

We successfully treated a 37-year-old male who had skeletal open bite with severe amelogenesis imperfecta (AI) with orthodontics, compression osteogenesis, and prosthodontics.

Case presentation

The patient was diagnosed with severe anterior open bite caused by severe AI. Corticotomy was performed on both buccal and palatal sides of the molar regions, and anchor plates were placed onto the bilateral zygomatic buttress and the center of the hard palate. After corticotomy, posterior maxillary segments were moved 3.5 mm superiorly to correct skeletal open bite with elastic chains. After 8-month, overbite had decreased by 2.0 mm. After further 5 months of prosthodontic preparation, orthodontic appliances were removed, and provisional crowns were set on all teeth. The anterior open bite was corrected, and ideal occlusion with a Class I molar relationship was achieved. The upper first molars were intruded 3.5 mm, resulting in 3.0^o counter-clockwise rotation of the mandible. The total active treatment period was 16 months. Acceptable occlusion with a good facial profile was well maintained throughout the 8-year retention period.

Conclusions

Our results indicate long-term stability after interdisciplinary treatment combining orthodontics, oral surgery, and prosthodontics in a patient with severe anterior open bite and AI.

http://bit.ly/2RV4ZG8

Teaching communication skills to OTL-HNS residents: multisource feedback and simulated scenarios

Abstract

Background

Effective communication has been linked to a reduction in adverse events and improved patient compliance. Currently in Otolaryngology – Head and Neck Surgery (OTL-HNS) residency programs, there is limited explicit teaching of communication skills. Our objective was to implement an educational program on communication skills for residents using multisource assessment in several simulation-based contexts throughout residency.

Methods

For three consecutive years, OTL-HNS residents were recruited to participate in a total of nine simulation-based clinical scenarios in which communication skills could be honed. This educational program was designed to provide instruction and practice of challenging ethics scenarios, with communication efficacy as a secondary goal. To facilitate this goal, a multisource assessment was paired with a debriefing process that involved attending staff, observing and participating residents, standardized patients, and invited content experts.

Results

Seventeen residents completed the curriculum for at least two consecutive years from 2009 to 2011. The internal-consistency reliability of the scenarios ranged from 0.88 to 0.96. The intraclass correlation was 0.19, as expected in this context. There was no statistical difference in the mean ratings of performance across post-graduate year (PGY) level (p = 0.201). Results from the random-intercept regression indicated that, on average, a learner's mean rating at baseline was 3.6/5 and increased significantly by 0.25 points per year (p < 0.05) as assessed by OTL-HNS staff members and peers. No significant improvement across time was found for ratings by non-medical assessors.

Conclusion

Implementing an educational program focused on communication skills using a multisource assessment in various contexts has shown to be potentially effective at our institution, and resulted for yearly improvement and consolidation of performance of OTL-HNS residents as judged by faculty and residents. The inclusion of a multisource assessment in the simulation curriculum is key to allow for the representation of different perspectives on communication skills, for both the assessment and the debriefing process. Future studies are needed to explore the possibility of fully integrating this educational program into residence training in order to support deliberate communication skills teaching.

http://bit.ly/2FXjin8

The effect of anti-CTLA4 treatment on peripheral and intra-tumoral T cells in patients with hepatocellular carcinoma

Abstract

Background

Checkpoint inhibitors have recently been approved for the treatment of patients with hepatocellular carcinoma (HCC). However, biomarkers, which will help identify patients responding to therapy, are missing. We recently tested the combination of anti-CTLA4 treatment (tremelimumab) with loco-regional therapy in patients with HCC and reported a partial response rate of 26%.

Methods

Here, we report updated survival analyses and results from our immune monitoring studies on peripheral blood mononuclear cells (PBMCs) and tumors from these patients.

Results

Tremelimumab therapy increased CD4⁺-HLA-DR⁺, CD4⁺PD-1⁺, CD8⁺HLA-DR⁺, CD8⁺PD-1⁺, CD4⁺ICOS⁺ and CD8⁺ICOS⁺ T cells in the peripheral blood of the treated patients. Patients with higher CD4⁺PD1⁺ cell frequency at baseline were more likely to respond to tremelimumab therapy. PD-1 expression was increased on alpha fetal protein (AFP) and survivin-specific CD8 T cells upon tremelimumab treatment. An increase of tumor infiltrating CD3⁺ T cells were also seen in these patients. Immunosequencing of longitudinal PBMC showed that one cycle of tremelimumab significantly decreased peripheral clonality, while no additional effects were seen after loco-regional therapy.

Conclusion

In summary, we observed a clear activation of T cell responses in HCC patients treated with tremelimumab and identified potential biomarkers which will help identify patients responding to immunotherapy with anti-CTLA4.

http://bit.ly/2MDAxdu

Vilnius Declaration on chronic respiratory diseases: multisectoral care pathways embedding guided self-management, mHealth and air pollution in chronic respiratory diseases

Over 1 billion people suffer from chronic respiratory diseases such as asthma, COPD, rhinitis and rhinosinusitis. They cause an enormous burden and are considered as major non-communicable diseases. Many patie...

http://bit.ly/2TkmMTB

Recurrent apocrine hidrocystoma of the external auditory canal

Publication date: Available online 28 January 2019

Source: American Journal of Otolaryngology

Author(s): Jack Birkenbeuel, Khodayar Goshtasbi, Hossein Mahboubi, Hamid R. Djalilian

http://bit.ly/2Wq182j

Prospective evaluation of pretreatment and intratreatment FDG PET‐CT SUV stability in primary head and neck cancer

Abstract

Purpose

To evaluate standardized uptake value (SUV) stability on pretreatment and intratreatment 18‐fluorodeoxyglucose (FDG) positron emission tomography‐computed tomography (PET‐CT) in patients undergoing definitive CRT for head and neck cancer (HNC).

Methods

Primary tumor and nodal volumes of interest (VOIs) from HNC patients were contoured on the pretreatment and intratreatment PET‐CT by two independent observers. SUV stability was measured with intersection calculations (DICE, overlap fraction, center to center) between the VOIs at threshold levels of 50%, 60%, 70%, 80%, and 90% of the SUV maximum.

Results

The mean calculated DICE of the 50%, 60%, 70%, 80%, 90% SUV threshold was 0.53, 0.48, 0.41, 0.28, and 0.12, respectively. The mean calculated overlap fraction was 0.71, 0.65, 0.58, 0.43, and 0.2, respectively. Center‐center difference demonstrates spatial variability of 7.8, 8.2, 8.6, 9.5, and 11.2 mm for these SUV subvolumes of interest.

Conclusions

HNC subvolumes defined by SUV thresholding technique in FDG PET‐CT imaging do not remain physically stable during (chemo)RT.

Highlights

All pretreatment and intratreatment SUV thresholds (50%‐90%) overlap indexes are low during the course of (chemo)radiation.

Pretreatment and intratreatment center to center variation further corroborates that all FDG threshold volumes do not remain stable during treatment.

No difference in SUV threshold stability was seen between p16 positive and negative tumors.

http://bit.ly/2DDR8eE

Adipose‐derived stem cells attenuate atopic dermatitis‐like skin lesions in NC/Nga mice

Abstract

There is an unmet need in novel therapeutics for atopic dermatitis (AD). We examined the effects of autologous adipose‐derived stem cells (ADSCs) on AD‐like skin lesions induced by the application of 2,4‐dinitrochlorobenzene (DNCB) in NC/Nga mice. Autologous ADSCs and ADSC‐conditioned medium (ADSC‐CM) were injected intralesionally three times. Clinical severity and histopathologic findings were compared in sham naïve control, saline‐treated, ADSC‐treated, ADSC‐CM‐treated, and 2.5% cortisone lotion‐applied animals. The severity index, skin thickness, mast cell number, as well as expression levels of thymic stromal lymphopoietin, CD45, chemoattractant receptor‐homologous molecule, chemokine ligand 9, and chemokine ligand 20 were significantly lower in mice treated with ADSC, ADSC‐CM, or 2.5% cortisone lotion.

Tissue levels of interferon‐ γ as well as serum levels of interleukin‐33 and immunoglobulin E levels were also decreased in those groups. We conclude that autologous ADSCs improved DNCB‐induced AD‐like skin lesions in NC/Nga mice by reducing inflammation associated with Th2 immune response and interferon‐γ.

This article is protected by copyright. All rights reserved.

http://bit.ly/2DFFmk1

Parental Expectation and Perception of CI Benefits in Their Implanted Wards

Abstract

Parents of implanted children develop a set of expectations prior to implantation about future performance and outcomes of their child. This set of expectations has an important impact on post-implant satisfaction levels. The position of the parent in the household makes them uniquely placed to assess the impact of implantation in the context within which the child grows up. There is strong need to find out expectations of parents from CI outcomes in implanted children. The functional benefits of CI may be measured by administering the parental perception of CI benefits in their implanted wards. The primary aim of the study was to find out different expectations of CI outcomes in parents of CI users and the perception of CI outcomes in the parents of CI users. Secondary aim was to find out the most important concerns of parents towards their implanted children. Twenty families with a child implanted for duration of more than 2 years were selected for the study. Two questionnaires (1) Parent Expectations Questionnaire for Cochlear Implants (Nemours children clinic) and (2) Parents and their cochlear implanted child Questionnaire (O'Neill Int J Pediatr Otorhinolaryngol 68: 149–160 2004) were administered on these parents. Results were analyzed qualitatively. Parents expected their implanted children to use the telephone, to be able to detect soft sounds, to listen in crowds, to be able to easily understand others, and to show improvement in communication skills. The quality of speech, process of implantation, to take time off for the appointments at the implant centre and making decision to proceed with implantation were main concerns of the parents. Parents have a high expectation from their implanted children in all domains of life i.e. communication abilities, social and academic skills. Parents have high positive views about the outcomes of the CI. However there are areas which need attention for a positive outcome from the point of view of parents of implanted children.

http://bit.ly/2sRpzs0

Obstructive sleep apnea in children and adolescents with and without obesity

Abstract

Purpose

To investigate the prevalence of obstructive sleep apnea (OSA) in children referred for obesity treatment, and to compare the prevalence with that of a normal-weight group. Moreover, we examined the association between Body Mass Index Standard Deviation Score (BMI SDS) and the Apnea–Hypopnea Index (AHI).

Methods

This cross-sectional study included 139 children aged 7–18 years with overweight/obesity (BMI SDS >1.28) recruited from an obesity treatment clinic. The normal-weight group consisted of 33 children (BMI SDS ≤ 1.28) aged 7–18 years recruited from schools. Sleep examinations were performed using a type 3 portable sleep monitor (Nox T3). OSA was defined as AHI ≥ 2. Height and weight were measured and the tonsillar size was clinically estimated using the Brodsky scale.

Results

The OSA prevalence was 44.6% in children with overweight/obesity compared with 9.1% in the normal-weight group (p = 0.0002), and the relative risk of OSA was 4.9 (95% CI 1.6–14.7). In a logistic regression, a one-unit increase in the BMI SDS increased the odds of having OSA by a factor of 1.92 independent of age, sex, tonsillar hypertrophy, and asthma (95% CI 1.33–2.76, p = 0.0005). A generalized linear regression adjusted for the same variables revealed an association between BMI SDS and AHI (a one-unit increase in the BMI SDS equaled an average increase in the AHI of 35% (95% CI 19–53%, p < 0.0001)).

Conclusions

In this study, children with overweight/obesity had a significantly higher prevalence of OSA compared with a normal-weight group. Increased BMI SDS was associated with increased AHI.

http://bit.ly/2FUkrfj

Parental Expectation and Perception of CI Benefits in Their Implanted Wards

Abstract

Parents of implanted children develop a set of expectations prior to implantation about future performance and outcomes of their child. This set of expectations has an important impact on post-implant satisfaction levels. The position of the parent in the household makes them uniquely placed to assess the impact of implantation in the context within which the child grows up. There is strong need to find out expectations of parents from CI outcomes in implanted children. The functional benefits of CI may be measured by administering the parental perception of CI benefits in their implanted wards. The primary aim of the study was to find out different expectations of CI outcomes in parents of CI users and the perception of CI outcomes in the parents of CI users. Secondary aim was to find out the most important concerns of parents towards their implanted children. Twenty families with a child implanted for duration of more than 2 years were selected for the study. Two questionnaires (1) Parent Expectations Questionnaire for Cochlear Implants (Nemours children clinic) and (2) Parents and their cochlear implanted child Questionnaire (O'Neill Int J Pediatr Otorhinolaryngol 68: 149–160 2004) were administered on these parents. Results were analyzed qualitatively. Parents expected their implanted children to use the telephone, to be able to detect soft sounds, to listen in crowds, to be able to easily understand others, and to show improvement in communication skills. The quality of speech, process of implantation, to take time off for the appointments at the implant centre and making decision to proceed with implantation were main concerns of the parents. Parents have a high expectation from their implanted children in all domains of life i.e. communication abilities, social and academic skills. Parents have high positive views about the outcomes of the CI. However there are areas which need attention for a positive outcome from the point of view of parents of implanted children.

http://bit.ly/2sRpzs0

Honeypot boulevard: understanding malicious activity via decoy accounts

Onaolapo, JO; (2019) Honeypot boulevard: understanding malicious activity via decoy accounts. Doctoral thesis (Ph.D), UCL (University College London). Green open access

http://bit.ly/2FTaVsD

Comparison of the oral microbiome of patients with generalized aggressive periodontitis and periodontitis-free subjects

Publication date: Available online 28 January 2019

Source: Archives of Oral Biology

Author(s): Susanne Schulz, Martin Porsch, Ivo Grosse, Katrin Hoffmann, Hans-Günter Schaller, Stefan Reichert

Abstract

Objective

The primary objectives of the study were to assess differences in complex subgingival bacterial composition between periodontitis-free persons and patients with generalized aggressive periodontitis (gAgP).

Background

The composition of the oral microbiota plays an important role for both oral and systemic diseases. However, the complex nature of the oral microbiome and its homeostasis is still poorly understood.

Material and methods

We compared the microbiome of 13 periodontitis-free persons to 13 patients with gAgP. The 16S rRNA genes were amplified, targeting the V3/V4 region using the MiSeq platform.

Results

In total, 1713 different bacterial species were mapped according to the Greengenes database. Using the Shannon index, no significant differences in alpha diversity were found between the two study groups. In principal component and linear discriminant analyses, disease-specific differences in beta diversity of the microbiome composition were evaluated. Bacteroidetes, Spirochaetes, and Synergistetes were more abundant in gAgP whereas Proteobacteria, Firmicutes, and Actinobacteria were associated with a healthy periodontium. At the bacterial species level, we showed that Porphyromonas gingivalis is the strongest indicator of gAgP. Treponema denticola and Tanerella forsythia of the "red complex" as well as Filifactor alocis were among the ten best biomarkers for gAgP.

Conclusions

These results broaden our knowledge of disease-specific differences in the microbial community associated with generalized AgP. A more complex view of the composition of the oral microbiome describes the etiology of generalized AgP in more detail. These results could help to individually adapt periodontal therapy in these patients.

http://bit.ly/2sQ1VvT

Perspektiven der Genomeditierung in der Hals-Nasen-Ohren-Heilkunde

Zusammenfassung

Hintergrund

Die Fortschritte in der DNA-Sequenzierung ermöglichen die genetischen Auslöser von Erkrankungen zu identifizieren. Zudem ist es heute möglich, mit „CRISPR-Cas9" („clustered regularly-interspaced short palindromic repeats und crispr-associated protein 9") genomische DNA-Sequenzen präzise und mit hoher Effizienz zu editieren. In kürzlich veröffentlichten präklinischen Studien wurde diese Technologie bereits für mögliche therapeutische Anwendungen evaluiert. Da auch in der HNO-Heilkunde viele Erkrankungen genetische Ursachen haben, birgt diese neue Technologie Chancen für neue Therapien.

Fragestellung

In diesem Übersichtsartikel erklären wir, wie die Genomeditierung als Therapieansatz genutzt werden könnte, und stellen dar, welche Erfolge in diesen Bereich bereits erreicht wurden und welche Herausforderungen auf dem Weg zur therapeutischen Nutzung bestehen.

Material und Methoden

Die Strategien zum Targeting von Genmutationen wurden anhand von Genomsequenzierungsdaten aus Online-Datenbanken und der Literatur entwickelt.

Ergebnisse

Kürzlich veröffentlichte Forschung an Tiermodellen hat gezeigt, dass die Genomeditierung erfolgreich für die Behandlung genetischer Erkrankungen benutzt werden kann. Dabei wurde z. B. in einer präklinischen Studie an Mäusen dominant-autosomaler Hörverlust erfolgreich mit CRISPR-Cas9 behandelt. Gleichermaßen könnten ähnliche Strategien auch für die Therapie von Kopf-Hals-Tumoren genutzt werden. Die größte Herausforderung scheint die Entwicklung eines Systems für die effiziente und sichere Applikation der therapeutischen Moleküle in den Zielgeweben der Patienten zu sein.

Schussfolgerungen

In der Theorie kann die Genomeditierung für mutationsspezifische genetische Therapien in der HNO genutzt werden. Jedoch müssen noch viele technologische Hürden auf dem Weg zur klinischen Anwendung überwunden werden.

http://bit.ly/2G2cL9Q

A serious thrombotic event in a patient with immune thrombocytopenia requiring intravenous immunoglobulin: a case report

Immune thrombocytopenia is an acquired autoimmune disease. Recently, there has been evidence of thrombotic risk in patients with immune thrombocytopenia, but the mechanism is still inconclusive. Intravenous im...

http://bit.ly/2RkMKoq

The global incidence and prevalence of anaphylaxis in children in the general population: a systematic review

Abstract

Background

Despite an increasing number of publications from individual countries and regions, there is still no systematic review of the global epidemiology of anaphylaxis in the general paediatric population.

Methods

We conducted a systematic review, using a protocol registered and published with the international prospective register of systematic reviews (PROSPERO). Results were reported following PRISMA guidelines. The search strategy was designed in Medline (ovid) and modified for Embase (ovid) and PubMed. Papers were screened by two independent reviewers following selection and exclusion criteria. Data extraction and risk of bias assessment were completed by the same two reviewers. Studies in adults only or those that did not report data in children separately were excluded.

Results

A final total of 59 articles were included. Of these, 5 reported cumulative incidence, 39 reported incidence rate and 17 reported prevalence data. The incidence of anaphylaxis in children worldwide varied widely, ranging from 1 to 761 per 100,000 person‐years for total anaphylaxis and 1 to 77 per 100,000 person‐years for food‐induced anaphylaxis. The definition of anaphylaxis from NIAID/FAAN was the most commonly used. Gender and ethnicity were demographic risk factors associated with anaphylaxis in children. Increasing total or food‐induced anaphylaxis incidence over time were reported by 19 studies.

Conclusion

The reported incidence of anaphylaxis in children varied widely. Studies in developing countries are underrepresented. To accurately compare anaphylaxis incidence between countries and investigate the time trends, further studies using a standardised definition across different countries are required.

This article is protected by copyright. All rights reserved.

http://bit.ly/2SdEhYG