Efficacy of off-label topical treatments for the management of androgenetic alopecia: a review

Androgenetic alopecia (AGA) is characterized by non-scarring follicle miniaturization. Despite the success of approved therapies, commonly reported side effects and the need for continual use has led to the investigation of alternative therapies. The aim of this paper is to critically review the success of off-label, topical monotherapies for treatment of AGA in men. A literature search was conducted to obtain randomized, controlled and blinded studies that investigated off-label, topical, monotherapies in male patients. Hair density, hair diameter and hair growth were used to evaluate treatment success. Fourteen off-label topical therapies were investigated among the 16 studies that met inclusion criteria. Nine off-label therapies were reported to produce a significantly greater improvement in hair restoration parameters (e.g. mean change from hair count and hair diameter) as compared to placebo (p < 0.05 for all treatments). In two studies, procyanidin oligomers exhibited greater efficacy over vehicle with response to mean change in hair density (hairs/cm2) (ps < 0.0001 at Week 24). In conclusion, prostaglandin analogs and polyphenols, such as latanoprost and procyanidin oligomers, can improve hair restoration parameters in male AGA patients, possibly through targeting mechanisms proposed in the etiology of AGA. The current evidence suggests short-term (24 weeks) use may provide benefit for hair loss patients; however, long-term efficacy and safety data are required

Blood and islet phenotypes indicate immunological heterogeneity in type 1 diabetes

This is an author-created, uncopyedited electronic version of an article accepted for publication in Diabetes. The American Diabetes Association (ADA), publisher of Diabetes, is not responsible for any errors or omissions in this version of the manuscript or any version derived from it by third parties. The definitive publisher-authenticated version is available in Diabetes in print and online at http://diabetes.diabetesjournals.orgThe erratum to this article is available in ORE at http://hdl.handle.net/10871/40335Studies in type 1 diabetes indicate potential disease heterogeneity, notably in the rate of β-cell loss, responsiveness to immunotherapies, and, in limited studies, islet pathology. We sought evidence for different immunological phenotypes using two approaches. First, we defined blood autoimmune response phenotypes by combinatorial, multiparameter analysis of autoantibodies and autoreactive T-cell responses in 33 children/adolescents with newly diagnosed diabetes. Multidimensional cluster analysis showed two equal-sized patient agglomerations characterized by proinflammatory (interferon-γ-positive, multiautoantibody-positive) and partially regulated (interleukin-10-positive, pauci-autoantibody-positive) responses. Multiautoantibody-positive nondiabetic siblings at high risk of disease progression showed similar clustering. Additionally, pancreas samples obtained post mortem from a separate cohort of 21 children/adolescents with recently diagnosed type 1 diabetes were examined immunohistologically. This revealed two distinct types of insulitic lesions distinguishable by the degree of cellular infiltrate and presence of B cells that we termed "hyper-immune CD20Hi" and "pauci-immune CD20Lo." Of note, subjects had only one infiltration phenotype and were partitioned by this into two equal-sized groups that differed significantly by age at diagnosis, with hyper-immune CD20Hi subjects being 5 years younger. These data indicate potentially related islet and blood autoimmune response phenotypes that coincide with and precede disease. We conclude that different immunopathological processes (endotypes) may underlie type 1 diabetes, carrying important implications for treatment and prevention strategies.JDRFNational Institute for Health Research (NIHR) Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust and King’s College LondonEuropean Union (EU FP7) award - Persistent Virus Infection in Diabetes Network Study Group (PEVNET)EU FP7 Large-Scale Focused Collaborative Research Project on Natural Immunomodulators as Novel Immunotherapies for Type 1 Diabetes (NAIMIT)EU FP7 Large-Scale Focused Collaborative Research Project on β-cell preservation through antigen-specific immunotherapy in Type 1 Diabetes: Enhanced Epidermal Antigen Delivery Systems (EE-ASI)National Institutes of Health (NIH)National Institute of Diabetes and Digestive and Kidney DiseasesNational Institute of Allergy and Infectious DiseasesEunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNational Center for Research ResourcesGeneral Clinical Research CenterAmerican Diabetes Association (ADA

Resectability and Ablatability Criteria for the Treatment of Liver Only Colorectal Metastases:Multidisciplinary Consensus Document from the COLLISION Trial Group

The guidelines for metastatic colorectal cancer crudely state that the best local treatment should be selected from a 'toolbox' of techniques according to patient- and treatment-related factors. We created an interdisciplinary, consensus-based algorithm with specific resectability and ablatability criteria for the treatment of colorectal liver metastases (CRLM). To pursue consensus, members of the multidisciplinary COLLISION and COLDFIRE trial expert panel employed the RAND appropriateness method (RAM). Statements regarding patient, disease, tumor and treatment characteristics were categorized as appropriate, equipoise or inappropriate. Patients with ECOG≤2, ASA≤3 and Charlson comorbidity index ≤8 should be considered fit for curative-intent local therapy. When easily resectable and/or ablatable (stage IVa), (neo)adjuvant systemic therapy is not indicated. When requiring major hepatectomy (stage IVb), neo-adjuvant systemic therapy is appropriate for early metachronous disease and to reduce procedural risk. To downstage patients (stage IVc), downsizing induction systemic therapy and/or future remnant augmentation is advised. Disease can only be deemed permanently unsuitable for local therapy if downstaging failed (stage IVd). Liver resection remains the gold standard. Thermal ablation is reserved for unresectable CRLM, deep-seated resectable CRLM and can be considered when patients are in poor health. Irreversible electroporation and stereotactic body radiotherapy can be considered for unresectable perihilar and perivascular CRLM 0-5cm. This consensus document provides per-patient and per-tumor resectability and ablatability criteria for the treatment of CRLM. These criteria are intended to aid tumor board discussions, improve consistency when designing prospective trials and advance intersociety communications. Areas where consensus is lacking warrant future comparative studies.</p

Update on current approaches to diagnosis and treatment of onychomycosis

Introduction: Onychomycosis is a chronic fungal infection of the nail bed, matrix or plate. It accounts for roughly 50% of all nail disease. As the prevalence of onychomycosis is increasing, a critical review of diagnostic techniques and treatment options is required. Areas covered: This review discusses the current diagnostic techniques associated with diagnosing onychomycosis, such as microscopy, culture, periodic acid Schiff stain (PAS) and polymerase chain reaction (PCR). Oral and topical therapies are also discussed, as well as, the utility of device-based treatments and combination therapy. Expert commentary: Culture for the diagnosis of onychomycosis is the gold standard; however, PCR is more sensitive and should be considered. In general, topical treatments are recommended for mild to moderate disease and oral treatments should be considered for moderate to severe disease. Combination therapy and device-based treatments may enhance cure rates, further study is required

Image quality and subject experience of quiet T1-weighted 7-T brain imaging using a silent gradient coil

OBJECTIVES: Acoustic noise in magnetic resonance imaging (MRI) negatively impacts patients. We assessed a silent gradient coil switched at 20 kHz combined with a T1-weighted magnetisation prepared rapid gradient-echo (MPRAGE) sequence at 7 T. METHODS: Five healthy subjects (21-29 years; three females) without previous 7-T MRI experience underwent both a quiet MPRAGE (Q-MPRAGE) and conventional MPRAGE (C-MPRAGE) sequence twice. Image quality was assessed quantitatively, and qualitatively by two neuroradiologists. Sound level was measured objectively and rated subjectively on a 0 to 10 scale by all subjects immediately following each sequence and after the whole examination (delayed). All subjects also reported comfort level, overall experience and willingness to undergo the sequence again. RESULTS: Compared to C-MPRAGE, Q-MPRAGE showed higher signal-to-noise ratio (10%; p = 0.012) and lower contrast-to-noise ratio (20%; p < 0.001) as well as acceptable to good image quality. Q-MPRAGE produced 27 dB lower sound level (76 versus 103 dB). Subjects reported lower sound level for Q-MPRAGE both immediate (4.4 ± 1.4 versus 6.4 ± 1.3; p = 0.007) and delayed (4.6 ± 1.4 versus 6.3 ± 1.3; p = 0.005), while they rated comfort level (7.4 ± 1.0 versus 6.1 ± 1.7; p = 0.016) and overall experience (7.6 ± 1.0 versus 6.0 ± 0.9; p = 0.005) higher. Willingness to undergo the sequence again was also higher, however not significantly (8.1 ± 1.0 versus 7.2 ± 1.3; p = 0.066). CONCLUSION: Q-MPRAGE using a silent gradient coil reduced sound level by 27 dB compared to C-MPRAGE at 7 T while featuring acceptable-to-good image quality and a quieter and more pleasant subject experience

Predicting food allergy: The value of patient history reinforced

BACKGROUND: EAACI guidelines emphasize the importance of patient history in diagnosing food allergy (FA) and the need for studies investigating its value using standardized allergy-focused questionnaires. OBJECTIVE: To determine the contribution of reaction characteristics, allergic comorbidities and demographics to prediction of FA in individuals experiencing food-related adverse reactions. METHODS: Adult and school-age participants in the standardized EuroPrevall population surveys, with self-reported FA, were included. Penalized multivariable regression was used to assess the association of patient history determinants with "probable" FA, defined as a food-specific case history supported by relevant IgE sensitization. RESULTS: In adults (N = 844), reproducibility of reaction (OR 1.35 [95% CI 1.29-1.41]), oral allergy symptoms (OAS) (4.46 [4.19-4.75]), allergic rhinitis (AR) comorbidity (2.82 [2.68-2.95]), asthma comorbidity (1.38 [1.30-1.46]) and male sex (1.50 [1.41-1.59]) were positively associated with probable FA. Gastrointestinal symptoms (0.88 [0.85-0.91]) made probable FA less likely. The AUC of a model combining all selected predictors was 0.85 after cross-validation. In children (N = 670), OAS (2.26 [2.09-2.44]) and AR comorbidity (1.47 [CI 1.39-1.55]) contributed most to prediction of probable FA, with a combined cross-validation-based AUC of 0.73. When focusing on plant foods, the dominant source of FA in adults, the pediatric model also included gastrointestinal symptoms (inverse association), and the AUC increased to 0.81. CONCLUSIONS: In both adults and school-age children from the general population, reporting of OAS and of AR comorbidity appear to be the strongest predictors of probable FA. Patient history particularly allows for good discrimination between presence and absence of probable plant FA

Field entomology data from Ethiopian trachoma population survey and laboratory transmission experiments for Musca sorbens and Chlamydia trachomatis

A population-based survey of 247 households was conducted in Shashemane district, Oromia Region, Ethiopia, between April and June 2018. Households were positively selected to include at least one child aged 1–9 years, resident on the day of enumeration. These datasets contain entomology from this survey; including fly-eye contact data, fly positivity for Chlamydia trachomatis and other entomological data (fly species, sex). Experiments were also conducted in the London School of Hygiene & Tropical Medicine to investigate transmission of Chlamydia trachomatis by Musca sorbens, those data are reported here

Identification of a novel recurrent 1q42.2-1qter deletion in high risk MYCN single copy 11q deleted neuroblastomas

Neuroblastoma is an aggressive embryonal tumor that accounts for ~15% of childhood cancer deaths. Hitherto, despite the availability of comprehensive genomic data on DNA copy number changes in neuroblastoma, relatively little is known about the genes driving neuroblastoma tumorigenesis. In this study, high resolution array comparative genome hybridization (CGH) was performed on 188 primary neuroblastoma tumors and 33 neuroblastoma cell lines to search for previously undetected recurrent DNA copy number gains and losses. A new recurrent distal chromosome 1q deletion (del(1)(q42.2qter)) was detected in seven cases. Further analysis of available array CGH datasets revealed 13 additional similar distal 1q deletions. The majority of all detected 1q deletions was found in high risk 11q deleted tumors without MYCN amplification (Fisher exact test p 5 5.61 3 1025). Using ultra-high resolution (~115 bp resolution) custom arrays covering the breakpoints on 1q for 11 samples, clustering of nine breakpoints was observed within a 12.5-kb region, of which eight were found in a 7-kb copy number variable region, whereas the remaining two breakpoints were colocated 1.4-Mb proximal. The commonly deleted region contains one miRNA (hsa-mir-1537), four transcribed ultra conserved region elements (uc.43-uc.46) and 130 protein coding genes including at least two bona fide tumor suppressor genes, EGLN1 (or PHD2) and FH. This finding further contributes to the delineation of the genomic profile of aggressive neuroblastoma, offers perspectives for the identification of genes contributing to the disease phenotype and may be relevant in the light of assessment of response to new molecular treatments