Serum Adipokines as Biomarkers for Surveillance of Metabolic Syndrome in Childhood Acute Lymphoblastic Leukemia Survivors in Low Middle-Income Countries.

BACKGROUND: Serum adipokines (leptin and adiponectin) are dysregulated before the onset of metabolic syndrome and hence may be useful biomarkers for screening of cardiometabolic late effects in childhood Acute Lymphoblastic Leukemia (cALL) survivors. METHODS: We compared serum adipokine levels between 40 cALL survivors (aged 10-18 years, >2 years from treatment completion) with similar controls. A multivariable logistic regression analysis was then done to assess the association of metabolic syndrome in cALL survivors with variables including adipokines and other metabolic parameters, demographic and treatment details, and Dual-energy X-ray absorptiometry scan-derived variables. RESULTS: Compared to controls, cALL survivors had a higher prevalence of metabolic syndrome (8/40 vs. 2/40, P = .044) and central obesity (11/40 vs. 4/40, P = 0.042). Median Serum Leptin (7.39 vs. 4.23 ng/ml, P = 0.207) levels and derived Leptin-Adiponectin Ratio (1.44 vs. 0.80, P = 0.598), were higher but not statistically different in our survivors compared to controls; Adiponectin levels were similar (6.07 vs. 5.01 µg/ml, P = 0.283). In the cALL survivors, overweight/obesity (odds ratio [OR] 21.9, P = 0.020) or higher Leptin levels (OR 1.11, P = 0.047), were independently associated with metabolic syndrome. CONCLUSIONS: Serum Leptin, independently predictive of metabolic syndrome in our cALL survivors, may be tested in larger studies to assess its utility in surveillance and initiation of early preventive measures.

Emerging and traditional 5-α reductase inhibitors and androgen receptor antagonists for male androgenetic alopecia.

INTRODUCTION: Androgenetic alopecia (AGA) is the most prevalent cause of male hair loss, often requiring medical and/or surgical intervention. The US FDA has approved topical minoxidil and oral finasteride for male AGA treatment. However, some AGA patients fail to respond satisfactorily to these FDA-approved treatments and/or may experience side effects, based on their individual profiles. To mitigate the shortcomings of these treatments, researchers are now exploring alternative treatments such as newer 5-α reductase inhibitors (5-ARIs) and androgen receptor antagonists (ARAs). AREAS COVERED: This article reviews the safety and effectiveness of well-known 5-α reductase inhibitors (5-ARIs) like finasteride and dutasteride, as well as the newer 5-ARIs, emerging androgen receptor antagonists (ARAs), and natural products such as saw palmetto and pumpkin seed oil in the treatment of male AGA. EXPERT OPINION: Although several newer 5-ARIs, ARAs, and natural products have exhibited promise in clinical trials, additional research is essential to confirm their safety and efficacy in treating male AGA. Until additional evidence is available for these agents, the preferred treatment choices for male AGA are the FDA-approved treatments, topical minoxidil, and oral finasteride.

Outcome of Open Repair of Thoracoabdominal Aortic Aneurysm in Takayasu Arteritis: A Retrospective Analysis.

BACKGROUND: Takayasu Arteritis (TA) is an immune mediated arteritis causing inflammation of the aorta and its branches, which can result in aortic aneurysms. Our aim is to describe the outcome of surgical management in these patients who presented with Thoracoabdominal aortic aneurysm (TAAA). METHODS: Between 2003 and 2023, 40 TA patients with TAAA underwent operative repair. RESULTS: There were 24 females and 16 males, in the age group of 19-53 years, with hypertension in 20 patients. Raised Erythrocyte sedimentation Rate was present in 13 patients. According to Crawford classification, there were 2 patients with type I, 2 with type II, 17 with type III, 12 patients with type IV and 7 with type V aneurysm. Multiple steno-occlusive lesions of aortic branches were present in 21 patients, with majority affecting the renal artery. Femoral Artery Femoral Vein Partial cardiopulmonary bypass was used for types I, II, III and V. Separate bypass to visceral branches was done in eight patients, of whom five had multiple bypasses and three patients only had renal bypass. Twelve patients underwent reimplantation of branches, out of which nine had multiple vessel reimplantation. Four patients underwent staged repair of the aneurysm, which included visceral debranching in the first day, followed by repair of the aneurysm in the next day. In the immediate postoperative period, ten patients developed acute kidney injury and two required dialysis. Other morbidities included acute respiratory distress syndrome (ARDS), spinal cord dysfunction, bleeding, and wound complications. Three patients expired in the immediate postoperative period. Mean duration of intensive care unit stay was 4.1 days and hospital stay was 12.7 days. Comparison of disease activity with morbidity and mortality was statistically insignificant. Patients were on follow-up for a range of 6 months to 14 years and median follow-up of 25 months. Over this time period four patients expired and four developed anastomotic pseudoaneurysm requiring intervention. On comparing the disease activity at the time of surgery with the long-term arteritis related complications that required intervention, the P value was 0.653 and hence statistically not significant. The 10-year survival rate is 84.4%. CONCLUSIONS: Surgical repair has good and satisfactory outcome, with low early and late mortality rates. Progression of disease can occur at any stage of the disease, hence indicating the need for long term follow-up and frequent imaging.

Global prevalence of onychomycosis in general and special populations: An updated perspective.

BACKGROUND: Onychomycosis is a chronic nail disorder commonly seen by healthcare providers; toenail involvement in particular presents a treatment challenge. OBJECTIVE: To provide an updated estimate on the prevalence of toenail onychomycosis. METHODS: We conducted a literature search using PubMed, Embase and Web of Science. Studies reporting mycology-confirmed diagnoses were included and stratified into (a) populations-based studies, and studies that included (b) clinically un-suspected and (c) clinically suspected patients. RESULTS: A total of 108 studies were included. Based on studies that examined clinically un-suspected patients (i.e., with or without clinical features suggestive of onychomycosis), the pooled prevalence rate of toenail onychomycosis caused by dermatophytes was 4% (95% CI: 3-5) among the general population; special populations with a heightened risk include knee osteoarthritis patients (RR: 14.6 [95% CI: 13.0-16.5]), chronic venous disease patients (RR: 5.6 [95% CI: 3.7-8.1]), renal transplant patients (RR: 4.7 [95% CI: 3.3-6.5]), geriatric patients (RR: 4.7 [95% CI: 4.4-4.9]), HIV-positive patients (RR: 3.7 [95% CI: 2.9-4.7]), lupus erythematosus patients (RR: 3.1 [95% CI: 1.2-6.3]), diabetic patients (RR: 2.8 [95% CI: 2.4-3.3]) and hemodialysis patients (RR: 2.8 [95% CI: 1.9-4.0]). The prevalence of onychomycosis in clinically suspected patients was significantly higher likely due to sampling bias. A high degree of variability was found in a limited number of population-based studies indicating that certain pockets of the population may be more predisposed to onychomycosis. The diagnosis of non-dermatophyte mould onychomycosis requires repeat sampling to rule out contaminants or commensal organisms; a significant difference was found between studies that performed single sampling versus repeat sampling. The advent of PCR diagnosis results in improved detection rates for dermatophytes compared to culture. CONCLUSION: Onychomycosis is an underrecognized healthcare burden. Further population-based studies using standardized PCR methods are warranted.

Treatment of onychomycosis in an era of antifungal resistance: Role for antifungal stewardship and topical antifungal agents.

A growing body of literature has marked the emergence and spread of antifungal resistance among species of Trichophyton, the most prevalent cause of toenail and fingernail onychomycosis in the United States and Europe. We review published data on rates of oral antifungal resistance among Trichophyton species; causes of antifungal resistance and methods to counteract it; and in vitro data on the role of topical antifungals in the treatment of onychomycosis. Antifungal resistance among species of Trichophyton against terbinafine and itraconazole-the two most common oral treatments for onychomycosis and other superficial fungal infections caused by dermatophytes-has been detected around the globe. Fungal adaptations, patient characteristics (e.g., immunocompromised status; drug-drug interactions), and empirical diagnostic and treatment patterns may contribute to reduced antifungal efficacy and the development of antifungal resistance. Antifungal stewardship efforts aim to ensure proper antifungal use to limit antifungal resistance and improve clinical outcomes. In the treatment of onychomycosis, critical aspects of antifungal stewardship include proper identification of the fungal infection prior to initiation of treatment and improvements in physician and patient education. Topical ciclopirox, efinaconazole and tavaborole, delivered either alone or in combination with oral antifungals, have demonstrated efficacy in vitro against susceptible and/or resistant isolates of Trichophyton species, with low potential for development of antifungal resistance. Additional real-world long-term data are needed to monitor global rates of antifungal resistance and assess the efficacy of oral and topical antifungals, alone or in combination, in counteracting antifungal resistance in the treatment of onychomycosis.

Potential emergence of terbinafine resistance by squalene epoxidase gene mutations: An 18-month cohort study of onychomycosis patients in the United States.

BACKGROUND: There is a concerning rise in antifungal-resistant dermatophytosis globally, with resistance to terbinafine conferred by point mutations in the squalene epoxidase (SQLE) gene. OBJECTIVES: Report changes in the prevalence and profile of SQLE mutations in onychomycosis patients in the United States. METHODS: A longitudinal cohort study of toenail samples was collected from suspected onychomycosis patients over an 18-month period from 2022 to 2023. Samples were submitted from across the United States and subjected to multiplex real-time polymerase chain reactions for dermatophyte detection, with further screening of SQLE mutations at four known hotspots (393Leu, 397Phe, 415Phe and 440His). RESULTS: A total of 62,056 samples were submitted (mean age: 57.5 years; female: 60.4%). Dermatophytes were detected in 38.5% of samples, primarily Trichophyton rubrum complex (83.6%) and T. mentagrophytes complex (10.7%). A survey of SQLE mutations was carried out in 22,610 dermatophyte samples; there was a significant increase in the prevalence of SQLE mutations between the first quarter of 2022 and the second quarter of 2023 (29.0 to 61.9 per 1000 persons). The Phe397Leu substitution was the predominant mutation; Phe415Ser and His440Tyr have also emerged which were previously reported as minor mutations in skin samples. The temporal change in mutation rates can be primarily attributed to the Phe415Ser substitution. Samples from elderly patients (>70 years) are more likely to be infected with the T. mentagrophytes complex including strains harbouring the Phe415Ser substitution. CONCLUSION: The prevalence of SQLE mutations among onychomycosis patients with Trichophyton infections may be underestimated. Older individuals may have a higher risk.

A comprehensive review of nondermatophyte mould onychomycosis: Epidemiology, diagnosis and management.

Nondermatophyte moulds (NDMs) are widely distributed and can be detected in association with mycotic nails; however, sometimes it can be challenging to establish the role of NDMs in the pathogenesis of onychomycosis (i.e. causative vs. contaminant). In studies where the ongoing invasive presence of NDMs is confirmed through repeat cultures, the global prevalence of NDMs in onychomycosis patients is estimated at 6.9% with the 3 most common genus being: Aspergillus, Scopulariopsis and Fusarium. NDM onychomycosis can, in many cases, appear clinically indistinguishable from dermatophyte onychomycosis. Clinical features suggestive of NDMs include proximal subungual onychomycosis with paronychia associated with Aspergillus spp., Fusarium spp. and Scopulariopsis brevicaulis, as well as superficial white onychomycosis in a deep and diffused pattern associated with Aspergillus and Fusarium. Longitudinal streaks seen in patients with distal and lateral onychomycosis may serve as an additional indicator. For diagnosis, light microscopic examination should demonstrate fungal filaments consistent with an NDM with at least two independent isolations in the absence of a dermatophyte; the advent of molecular testing combined with histological assessment may serve as an alternative with improved sensitivity and turnover time. In most instances, antifungal susceptibility testing has limited value. Information on effective treatments for NDM onychomycosis is relatively scarce, unlike the situation in the study of dermatophyte onychomycosis. Terbinafine and itraconazole therapy (continuous and pulsed) appear effective to varying extents for treating onychomycosis caused by Aspergillus, Fusarium or Scopulariopsis. There is scant literature on oral treatments for Neoscytalidium.

Mapping the Global Spread of T. indotineae: An Update on Antifungal Resistance, Mutations, and Strategies for Effective Management.

INTRODUCTION: The global spread of Trichophyton indotineae presents a pressing challenge in dermatophytosis management. This systematic review explores the current landscape of T. indotineae infections, emphasizing resistance patterns, susceptibility testing, mutational analysis, and management strategies. METHODS: A literature search was conducted in November 2023 using Embase, PubMed, Scopus, and Web of Science databases. Inclusion criteria covered clinical trials, observational studies, case series, or case reports with T. indotineae diagnosis through molecular methods. Reports on resistance mechanisms, antifungal susceptibility testing, and management were used for data extraction. RESULTS AND DISCUSSION: A total of 1148 articles were identified through the systematic search process, with 45 meeting the inclusion criteria. The global spread of T. indotineae is evident, with cases reported in numerous new countries in 2023. Tentative epidemiological cut-off values (ECOFFs) suggested by several groups provide insights into the likelihood of clinical resistance. The presence of specific mutations, particularly Phe397Leu, correlate with higher minimum inhibitory concentrations (MICs), indicating potential clinical resistance. Azole resistance has also been reported and investigated in T. indotineae, and is a growing concern. Nevertheless, itraconazole continues to be an alternative therapy. Recommendations for management include oral or combination therapies and individualized approaches based on mutational analysis and susceptibility testing. CONCLUSION: Trichophyton indotineae poses a complex clinical scenario, necessitating enhanced surveillance, improved diagnostics, and cautious antifungal use. The absence of established clinical breakpoints for dermatophytes underscores the need for further research in this challenging field.

Safety of Procalcitonin Guided Early Discontinuation of Antibiotic Therapy among Children Receiving Cancer Chemotherapy and Having Low-Risk Febrile Neutropenia: A Randomized Feasibility Trial (ProFenC Study).

In low-risk febrile neutropenia (LR-FN), the safety of early discontinuation of empiric antibiotics without marrow recovery is not well established. This study aimed to evaluate the safety of procalcitonin (PCT) guided early discontinuation of antibiotics in LR-FN. In this trial, children with LR-FN with an afebrile period of at least 24 h, sterile blood culture, and negative/normalized PCT were randomized at 72 h of starting antibiotics into two groups: intervention arm and standard arm. The antibiotics were stopped in the intervention arm regardless of absolute neutrophil count (ANC), while in the standard arm, antibiotics were continued for at least 7 days or until recovery of ANC (>500/mm3). The primary objective was to determine the treatment failure rates, and the secondary objective was to compare the duration of antibiotics and all-cause mortality between the two arms. A total of 46 children with LR-FN were randomized to either the intervention arm (n = 23) or the standard arm (n = 23). Treatment failure was observed in 2/23 (8.7%) of patients in the intervention arm compared to 1/23 (4.3%) in the standard arm [RR: 2 (95% CI: 0.19-20.6); p = 0.55]. The median duration of antibiotics in the intervention arm and standard arm were 3 days vs 7 days (P= <0.001). There was no mortality in this study. PCT-guided early discontinuation of empirical antibiotics in LR-FN is feasible. There was no significant difference observed in treatment failure between the early discontinuation of antibiotics vs standard therapy. The total duration of antibiotic exposure was significantly lesser in the discontinuation arm. Further, larger multicenter studies are needed to confirm the finding of this study.

Concepts, Terminology, and Innovations in Follicular Unit Excision Hair Restoration Surgery.

Follicular unit excision (FUE) has emerged as the preferred method for hair transplants. Standardized terms and definitions established by members of the International Society of Hair Restoration Surgery and prominent hair restoration surgeons have become the standard, enabling effective knowledge sharing. This chapter provides an overview of the terminology relating to the field.The historical evolution of FUE and its pivotal role in modern hair transplantation is summarized. Anatomical terminology and graft-related definitions follow, providing insights into the scalp's complex structures and graft characteristics. The subsequent sections detail the terminology associated with graft excision and extraction, shedding light on the precise techniques and procedures employed. An exploration of various FUE techniques and the evolving landscape of FUE devices underscores the continual refinement of hair restoration practices. The chapter proceeds to discuss the "safe'" scalp donor zones, donor assessment terminology, and elements in identifying the optimal donor area for a successful FUE procedure. Additionally, punch dynamics and technique characteristics are examined, emphasizing their pivotal role in achieving superior FUE outcomes. The chapter concludes by discussing the classification of punches and graft evaluation terms, offering insights into the tools, and criteria used to assess graft quality and viability.

Relative impact of traditional vs. newer oral antifungals for dermatophyte toenail onychomycosis: a network meta-analysis study.

BACKGROUND: There is a paucity of evidence regarding the relative therapeutic efficacy of treatments for onychomycosis. OBJECTIVES: We determined the relative efficacy of monotherapies for dermatophyte toenail onychomycosis with Bayesian network meta-analyses (NMAs). METHODS: We searched PubMed, Scopus, EMBASE (Ovid) and CINAHL to identify studies that investigated the efficacy of monotherapy with oral antifungals for dermatophyte toenail onychomycosis in adults. In this paper, 'regimen' corresponds to a given agent and its dosage. The relative effects and surface under the cumulative ranking curve (SUCRA) values of the various regimens were estimated; evidence quality was assessed at the study level and across networks. RESULTS: Data from 21 studies were used. Our two efficacy-related endpoints were: (i) mycological and (ii) complete cure at 1 year; safety--related endpoints were: (i) 1-year count of any adverse event (AE), (ii) 1-year odds of discontinuation due to any AE, (iii) 1-year odds of discontinuation due to liver issues. Thirty-five regimens were identified; the newer agents among these included posaconazole and oteseconazole. We compared the efficacy of newer regimens with traditional ones like 'terbinafine 250 mg daily for 12 weeks' and 'itraconazole 200 mg daily for 12 weeks. We found that an agent's dosage was associated with its efficacy; for example, the 1-year odds of mycological cure with terbinafine 250 mg daily for 24 weeks (SUCRA = 92.4%) were significantly greater than those of terbinafine 250 mg daily for 12 weeks (SUCRA = 66.3%) (odds ratio 2.62, 95% credible interval 1.57-4.54). We also found that booster regimens can increase efficacy. Our results showed that some triazoles could be more effective than terbinafine. CONCLUSIONS: This is the first NMA study of monotherapeutic antifungals - and their various dosages - for dermatophyte toenail onychomycosis. Our findings could provide guidance for the selection of the most appropriate antifungal agent, especially amid the growing concerns about terbinafine resistance.

Efficacy and safety of zinc in the prevention of oral mucositis in children with cancer receiving intensified chemotherapy: A randomized double-blind placebo-controlled trial.

BACKGROUND AND AIMS: A limited number of safe and effective preventive options for oral mucositis (OM) are available. This randomized, double-blind, placebo-controlled trial aimed to evaluate the efficacy and safety of zinc in preventing OM in children with cancer receiving intensified chemotherapy. METHODS: Children aged 3-18 years were randomized to receive oral zinc at 1 mg/kg/dose daily for 14 days or a placebo at the same doses and schedule. The primary outcome of this study was to determine the effect of oral zinc in the prevention of OM, and secondary outcomes included any adverse effect of oral zinc, the severity and duration of OM, and the need for hospitalizations. RESULTS: A total of 90 children were randomized to either the oral zinc (n = 44) or placebo group (n = 46). The incidence of OM in the zinc group was 20.5%, while that in the placebo group was 19.6% (p = .91; risk ratio: 1.04, 95% CI 0.45-2.30). There were no significant adverse events of the drug observed. There were no significant differences between the two groups in the severity (p = .79), the mean time of onset (p = .09), the mean duration of OM (p = .18), and the need for hospitalizations (p = 1.0). CONCLUSIONS: Among children on cancer chemotherapy, there was no decrease in the incidence of OM observed with oral zinc at a dose of 1 mg/kg/day. No significant adverse events were observed with administering oral zinc. Further research is warranted to test higher doses of oral zinc with longer duration for a clinically significant effect.

Sarcocystis cruzi (Hasselmann, 1923) Wenyon, 1926: redescription, molecular characterization and deposition of life cycle stages specimens in the Smithsonian Museum.

Currently, 7 named Sarcocystis species infect cattle: Sarcocystis hirsuta, S. cruzi, S. hominis, S. bovifelis, S. heydorni, S. bovini and S. rommeli; other, unnamed species also infect cattle. Of these parasites of cattle, a complete life cycle description is known only for S. cruzi, the most pathogenic species in cattle. The life cycle of S. cruzi was completed experimentally in 1982, before related parasite species were structurally characterized, and before the advent of molecular diagnostics; to our knowledge, no archived frozen tissues from the cattle employed in the original descriptions remain for DNA characterization. Here, we isolated DNA from a paraffin-embedded kidney of a calf experimentally infected with S. cruzi in 1980; we then sequenced portions of 18S rRNA, 28S rRNA, COX1 and Acetyl CoA genes and verified that each shares 99­100% similarity to other available isolates attributed to S. cruzi from naturally infected cattle. We also reevaluated histological sections of tissues of calves experimentally infected with S. cruzi in the original description, exploiting improvements in photographic technology to render clearer morphological detail. Finally, we reviewed all available studies of the life cycle of S. cruzi, noting that S. cruzi was transmitted between bison (Bison bison) and cattle (Bos taurus) and that the strain of parasite derived from bison appeared more pathogenic than the cattle strain. Based on these newfound molecular, morphological and physiological data, we thereby redescribed S. cruzi and deposited reference material in the Smithsonian Museum for posterity.

Effect of Imatinib Mesylate on Growth in Pediatric Chronic Myeloid Leukemia: A Systematic Review and Meta-analysis.

The outcomes of pediatric chronic myeloid leukemia (CML) have improved with the use of imatinib mesylate (IM). Multiple reports of growth deceleration with IM have raised concerns, necessitating careful monitoring and evaluation in children with CML. We systematically searched the databases of PubMed, EMBASE, Scopus, CENTRAL, and conferences-abstracts, reporting the effect of IM on growth among children with CML, and published in the English language from inception till March 2022. For observational studies, the modified Newcastle Ottawa Scale was used to assess the risk of bias. Pooled estimates were derived using a random-effects meta-analysis, and heterogeneity was assessed using Cochrane Q statistic test of heterogeneity and I2 statistic. Of the 757 studies identified through electronic search, 15 (n=265) were included in the final analysis. Six studies (n=178) were included in the meta-analysis of the primary outcome. There was a significant deleterious effect of IM on height-standardized mean difference (SMD): -0.52 (95% CI: -0.76; -0.28) ( I2 =13%). The adverse effect of IM on height was significant among studies with a follow-up period <3 years [SMD: -0.66 (95% CI: -0.93, -0.40), I2 =0%, P =0.59] but not in studies with follow-up period ≥3 years [SMD: -0.26 (95% CI: -0.63, 0.11), I2 =0, P =0.44], indicating that the effect of IM on height is a short-term effect. The effect of IM on height was not dependent upon pubertal status at the initiation of therapy. Prospective studies with adequate sample size are required to confirm the findings of the effect of IM on height in children with CML.

Efficacy and Safety of Olanzapine for the Prevention of Chemotherapy-induced Nausea and Vomiting in Children: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

Chemotherapy-induced nausea and vomiting (CINV) remain the most distressing event in patients receiving highly emetogenic chemotherapy (HEC) and moderately emetogenic chemotherapy (MEC). This meta-analysis was conducted to evaluate the efficacy and safety of olanzapine containing regimen in preventing CINV in children on HEC and MEC. We searched PubMed, Embase, and Cochrane central register of controlled trials electronic databases to identify randomized clinical trials that compared 2 groups who either got olanzapine (olanzapine group) or placebo/no olanzapine (control group) for the prevention of CINV in children. The primary outcome was to determine the efficacy of olanzapine (complete response). The secondary outcomes were nausea control, the need for rescue medications, and adverse events of olanzapine. Three randomized clinical trials (n=394 patients) were included in this meta-analysis (olanzapine group, n=194, and placebo/control group, n=200). The pooled analysis of this meta-analysis found that olanzapine had a higher complete response in all phases of emesis in the HEC group and only in the acute phase in HEC/MEC groups compared with the control group. Olanzapine had higher nausea control in all phases of HEC but no nausea control in HEC/MEC. Olanzapine also reduced the need for rescue medications. A significant number of patients in the olanzapine group experienced somnolence (grades 1 and 2), but none of the participants discontinued the study due to side effects. In conclusion, this meta-analysis showed that olanzapine significantly prevented CINV in HEC. There was also a lesser need for rescue medications in the olanzapine group. Somnolence was higher in the olanzapine group, but it was clinically insignificant.

Factors Associated With Musculoskeletal Pain Among Hair Transplant Surgeons: Analyses of Survey Data and Review of the Literature.

BACKGROUND: The prevalence of work-related musculoskeletal disorders (WRMD) is increasing among all surgical specialties. OBJECTIVE: Results of a cross-sectional survey of hair transplant surgeons were analyzed, with the aims to (1) determine the prevalence of WRMD, (2) assess risk factors associated with musculoskeletal (MSK) symptoms, and (3) identify mitigation measures. MATERIALS AND METHODS: A survey pertaining to demographics, MSK-related symptoms and its impacts, and pain mitigation measures taken, if any, were distributed to 834 hair transplant surgeons. Risk factors associated with pain severity were assessed using linear regression. RESULTS: Overall, 78.5% (73 of 93) respondents had experienced pain when performing surgery. Musculoskeletal symptoms were most severe in the neck, followed by upper/lower back, and extremities. Number of grafts performed per session of follicular unit extraction positively correlated with pain severity; female surgeons and surgeons aged >71 years were at higher risk. A majority expressed concern that WRMD may limit their career and agreed to a need for improved workplace education. Strength training and ergonomic improvements of surgical procedure were not commonly adopted. CONCLUSION: In sum, WRMD can be debilitating in health care professionals. Workplace ergonomic adjustments and physical exercise programs may be warranted to better mitigate MSK symptoms.

Combatting antifungal resistance: Paradigm shift in the diagnosis and management of onychomycosis and dermatomycosis.

Antifungal resistance has become prevalent worldwide. Understanding the factors involved in spread of resistance allows the formulation of strategies to slow resistance development and likewise identify solutions for the treatment of highly recalcitrant fungal infections. To investigate the recent explosion of resistant strains, a literature review was performed focusing on four main areas: mechanisms of resistance to antifungal agents, diagnosis of superficial fungal infections, management, and stewardship. The use of traditional diagnostic tools such as culture, KOH analysis and minimum inhibitory concentration values on treatment were investigated and compared to the newer techniques such as molecular methods including whole genome sequencing, and polymerase chain reaction. The management of terbinafine-resistant strains is discussed. We have emphasized the need for antifungal stewardship including increasing surveillance for resistant infection.

Systematic review of newer agents for the management of alopecia areata in adults: Janus kinase inhibitors, biologics and phosphodiesterase-4 inhibitors.

Management options for moderate-to-severe alopecia areata (AA) are limited owing to a lack of safe and effective treatments suitable for long-term use. However, newer agents have the potential to induce and maintain hair regrowth in patients with a better side-effects profile compared to systemic steroids or conventional systemic agents. In this article, we conducted a systematic review of newer agents, including Janus kinase (JAK) inhibitors, biologics and phosphodiesterase-4 (PDE-4) inhibitors, for the treatment of AA in adult patients evaluated in randomized controlled trials (RCTs) using the Severity of Alopecia Tool score. A literature search was performed on PubMed and ClinicalTrials.gov, which identified 106 items with 12 RCTs eligible for review. Information regarding the treatment regimen, duration, endpoints, efficacy and adverse events were extracted; product monograph information was also summarized for approved agents with or without indications for AA. Overall, current data suggest the oral JAK inhibitors (baricitinib, ritlecitinib, deuruxolitinib, brepocitinib) as a promising new class of agents that can induce significant hair regrowth, with mild to moderate adverse effects. Baricitinib recently received US FDA approval for the treatment of severe AA, while ritlecitinib and deuruxolitinib have received the breakthrough therapy designation for AA. In contrast, PDE-4 inhibitors (apremilast) and the biologics (dupilumab, secukinumab and aldesleukin) appear to have limited efficacy thus far. Results from ongoing and future long-term studies could shed light on the utility of the newer agents in altering the progression of AA.

Strategies for the enhancement of nail plate permeation of drugs to treat onychomycosis.

Onychomycosis is caused by dermatophytes, non-dermatophytes and yeasts. It has a global prevalence of 5.5%, requires long treatment periods, and has high relapse rates following therapy. Oral antifungals are generally the most common treatment. While effective, they have limitations such as drug-drug interactions, hepatotoxicity and adverse side effects; thus, they cannot be used in several populations. Topical antifungals do not have the safety limitations but are typically not as effective. The primary challenge of topical treatment is the permeation of drug molecules across the nail plate barrier, which is a highly cross-linked keratin network. The use of drugs and formulations with favourable characteristics such as small size, absence of lipophilicity, hydrophilic nature, hydrating properties and appropriate pH can greatly improve permeation. Here, we review physical, nanoparticle-based, formulation-based, mechanical and chemical drug delivery strategies to improve the permeation of drugs across the nail plate.

Efficacy and safety of vemurafenib in Langerhans cell histiocytosis (LCH): A systematic review and meta-analysis.

Almost half of the patients with Langerhans cell histiocytosis (LCH) are refractory to primary induction chemotherapy or undergo reactivation. The ideal treatment modality for refractory/relapsed LCH is yet not evidenced. This review aimed to determine the efficacy and safety of vemurafenib (a BRAF pathway inhibitor) in LCH, particularly the refractory/relapsed cases. The literature search was conducted using PubMed, Embase, CENTRAL, and abstracts published in the SIOP meetings. Studies that described the outcome of patients of LCH being treated with vemurafenib, alone or in combination, were included. A total of 416 studies were screened, and after applying exclusion criteria, 22 studies (n = 107) were included in the final analysis. The first-line therapy was prednisolone plus vinblastine for most patients (n = 92, 86%), and vemurafenib was started upfront in 3 patients (3%). The median time to first clinical response with vemurafenib was one week. The median time to best response was 5.25 months. Out of 107 patients, 62 patients (58%) had ultimately no active disease (NAD) while 39 (36%) had active disease better (ADB), making the overall response rate (ORR) of 101/107, ie, 94.4% (CI 0.88; 0.98). The main adverse effects of vemurafenib were rash or photosensitivity (47%) and other cutaneous adverse events (15%). Vemurafenib is highly efficacious and safe in the treatment of refractory LCH; however, the timing of its commencement and duration of therapy is yet to be established. Larger prospective collaborative trials are needed to answer the appropriate treatment duration and effective maintenance therapy approach.