Efficacy of Acupuncture and Moxibustion in Alopecia: A Narrative Review.

Acupuncture is the practice of applying needles to target specific pressures points in the body. Since originating in China, acupuncture has been practiced for thousands of years to treat numerous conditions including chronic pain and mood disorders. Alopecia is a common dermatologic condition associated with psychological distress and decreased quality of life. Although it remains underexplored in western medicine, recent evidence suggests that acupuncture may be efficacious in the treatment of alopecia. In this review, we discuss the available evidence describing the efficacy of acupuncture or moxibustion alone (ACU) and in combination with other traditional and alternative interventions (ACU + TRAD) for hair loss. Additionally, the proposed physiologic mechanisms, targeted acupuncture points, and the benefits and barriers to treatment will be further described. An exploratory search using PubMed, EMBASE and Scopus databases was performed for studies that evaluated the effect of acupuncture and moxibustion on alopecia. In these studies, both ACU and ACU + TRAD were efficacious for numerous etiologies of hair loss including alopecia areata, androgenetic alopecia, and seborrheic alopecia. Given their ability to modulate the immune system, as well as neuronal networks associated with emotional cognition, the most frequently targeted acupoints were ST 36, GV 20, and LR 3. The proposed mechanistic effect is dependent upon disease etiology and is theorized to be twofold: reduction of inflammation and decrease in testosterone levels. The limited side effect profile of acupuncture makes it an advantageous treatment option, however, factors including cost, time, limited access, and aversion to needles may serve as barriers to treatment.

Association between nailfold capillaroscopy abnormalities and autoimmune disease in pediatric populations.

OBJECTIVE: Time to diagnosis of autoimmune disease in pediatric populations can take years but nailfold capillaroscopy (NFC) may identify early signs of autoimmune disease. The aim of this study is to assess the association between nailfold capillary abnormalities and autoimmune disease in children. METHODS: A systematic search of PubMed, EMBASE, and Scopus was performed to identify all studies published before March 17, 2021. Observational studies reporting NFC outcomes in children with autoimmune disease and healthy controls (HC) were eligible for inclusion. Odds ratios (OR) and 95% confidence intervals (CI) were pooled using a random-effects meta-analytical model. RESULTS: Nine of 3665 studies reporting on 641 patients (398 subjects, 243 controls) were included. Pediatric patients with autoimmune disease were 9.88 (95% CI 3.16-30.87, I2  = 80.1%) times more likely to have abnormal nailfold capillaries than HC. Of the capillaroscopic features, dilated capillaries (OR 27.90, 95% CI 2.17-349.05, I2  = 59.9%) were the most likely abnormality observed on NFC. This was followed by the likelihood of reduced capillary density (<7 capillaries/mm) (OR 19.91, 95% CI 3.79-105.52, I2  = 0%), giant capillaries (OR 12.87, 95% CI 2.38-69.45, I2  = 0%), hemorrhages (OR 13.89, 95% CI 5.34-36.16, I2  = 0%), and avascularity (OR 10.38, 95% CI 2.20-49.04, I2  = 0%). CONCLUSIONS: Children with autoimmune disease are significantly more likely to have nailfold capillary abnormalities. NFC may be useful in identifying early signs of underlying rheumatic disease and potentially decrease the time to diagnosis for this patient population.

Effect of Medical Therapy in Allergic Rhinitis: A Systematic Review and Meta-Analysis.

BACKGROUND: Intranasal corticosteroids (INCS), oral antihistamines (POAH), and allergen-specific immunotherapy (ASIT) are widely used in the treatment of allergic rhinitis (AR); however, appraisal of treatment effect has been heterogenous, and few studies have interpreted these outcomes in context with measures of nasal airflow. OBJECTIVE: To provide a systematic review and meta-analysis of randomized placebo-controlled trials for common therapy classes for AR to assess standardized treatment effect on validated patient-reported outcomes and physiologic measures of airflow. METHODS: A systematic search was performed in PubMed, Scopus, OVID, and Cochrane library databases to identify randomized controlled trials meeting inclusion criteria. Treatment effects of INCS, POAH, and ASIT on total nasal symptom score (TNSS), visual analog scale (VAS), Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), and peak nasal inspiratory flow (PNIF) were analyzed by meta-analysis. RESULTS: Twenty-two studies with 4673 AR patients were identified, with 5 INCS, 8 POAH, and 9 ASIT trials. INCS improved TNSS (mean difference [MD] 0.90; P = .002) and PNIF (MD 13.31 L/min [P = .0007]. POAH improved quality of life assessed by RQLQ [MD 0.36; P < .001], but no improvement was found in PNIF. ASIT improved RQLQ [MD 0.65; P < .001], with a trend toward improvement in TNSS. CONCLUSION: Overall, INCS resulted in a clinically and statistically meaningful improvement in symptom scores and physiologic measures in AR. POAH and ASIT both improved symptom scores and quality of life, but their impacts upon nasal airflow are uncertain. There is a lack of studies assessing the effect of INCS on quality of life and the effect of POAH on symptom severity, particularly for mild AR. Future studies should assess the effect of treatment for each of these patient-reported measures.

Impact of Treatment for Nasal Cavity Disorders on Sleep Quality: Systematic Review and Meta-analysis.

OBJECTIVE: To determine the impact of treatment for patients with nasal obstruction secondary to allergic rhinitis (AR) and nasal septal deviation (NSD) on sleep quality. DATA SOURCES: Primary studies were identified though PubMed, Scopus, Cochrane Library, and Web of Science. REVIEW METHODS: A systematic review was performed by querying databases for articles published through August 2020. Studies were included that reported on objective sleep parameters (apnea-hypopnea index) and sinonasal and sleep-specific patient-reported outcome measures: Rhinoconjunctivitis Quality of Life Questionnaire, Nasal Obstruction Symptom Evaluation, Epworth Sleepiness Scale (EpSS), and Pittsburgh Sleep Quality Index (PSQI). RESULTS: The database search yielded 1414 unique articles, of which 28 AR and 7 NSD studies were utilized for meta-analysis. A total of 9037 patients (8515 with AR, 522 with NSD) were identified with a mean age of 35.0 years (35.3 for AR, 34.0 for NSD). Treatment for AR and NSD significantly improved subjective sleep quality. For AR, the EpSS mean difference was -1.5 (95% CI, -2.4 to -0.5; P = .002) and for the PSQI, -1.7 (95% CI, -2.1 to -1.2; P < .00001). For NSD, the EpSS mean difference was -3.2 (95% CI, -4.2 to -2.2; P < .00001) and for the PSQI, -3.4 (95% CI, -6.1 to -0.6; P = .02). CONCLUSION: Subjective sleep quality significantly improved following treatment for AR and NSD. There were insufficient data to demonstrate that objective metrics of sleep quality similarly improved.

Eosinophils and melanoma: Implications for immunotherapy.

New therapies such as immune checkpoint blockers (ICB) have offered extended survival to patients affected by advanced melanoma. However, ICBs have demonstrated debilitating side effects on the joints, liver, lungs, skin, and gut. Several biomarkers have been identified for their role in predicting which patients better tolerate ICBs. Still, these biomarkers are limited by immunologic and genetic heterogeneity and the complexity of translation into clinical practice. Recent observational studies have suggested eosinophil counts, and serum levels of eosinophil cationic protein are significantly associated with prolonged survival in advanced-stage melanoma. It is likely that eosinophils thereby modulate treatment response through mechanisms yet to be explored. Here, we review the functionality of eosinophils, their oncogenic role in melanoma and discuss how these mechanisms may influence patient response to ICBs and their implications in clinical practice.

Emerging Developments in Management of Melanoma During the COVID-19 Era.

In March 2020, the designation of the COVID-19 outbreak as a worldwide pandemic marked the beginning of an unprecedented era in modern medicine. Facing the possibility of resource precincts and healthcare rationing, leading dermatological and cancer societies acted expeditiously to adapt their guidelines to these contingencies. Melanoma is a lethal and aggressive skin cancer necessitating a multidisciplinary approach to management and is associated with significant healthcare and economic cost in later stages of disease. In revisiting how the pandemic transformed guidelines from diagnosis and surveillance to surgical and systemic management of melanoma, we appraise the evidence behind these decisions and their enduring implications.

Immune Checkpoint Inhibitors for Advanced Cutaneous Squamous Cell Carcinoma: A Systematic Review with Meta-Analysis.

BACKGROUND: Results of early trials led to FDA approval of immune checkpoint inhibitors (ICIs) for advanced and recurrent/metastatic (R/M) cutaneous squamous cell carcinoma (CSCC). Updated data from these trials are pending and extent of survival outcomes is undetermined. OBJECTIVE: The aim of this study was to assess the efficacy of ICIs in advanced CSCC, comprising locally advanced (LA), locoregionally advanced (LR), and recurrent or metastatic (R/M) disease. PATIENTS AND METHODS: A systematic review of four databases (PubMed, Scopus, OVID, Cochrane) and meta-analysis of proportions was performed. Phase I and II prospective clinical trials were included. RESULTS: Six trials evaluating cemiplimab (n = 3) and pembrolizumab (n = 3) were eligible for inclusion. Overall survival (OS) was not reached at data-cutoff. Pooled analysis of 392 patients demonstrated that ICIs conferred an objective response rate (ORR) of 42.43% (95% CI 37.53-47.45) and disease control rate (DCR) of 58.05% (95% CI 53.04-62.95). Patients with LR or distant metastatic lesions achieved equivalent ORRs and DCRs. Duration of response (DOR) was not reached in all trials and 92% of all responders continued to have therapeutic response at data cut-off. Tolerability was favorable, with only 27.12% (95% CI 10.89-47.38) of patients experiencing grade ≥ 3 adverse events. CONCLUSION: Surgical treatment of CSCC remains the guideline-based standard of care for curative intent of local, LA, and LR disease. ICIs demonstrate promising results for LA, LR, and R/M CSCC not amenable to surgery. Endpoints assessing survival and durability of response have not been reached, warranting additional trials exploring neoadjuvant or adjuvant therapy in combination with local treatment.

Systematic review of measures of disease severity in rhinitis.

BACKGROUND: Rhinologists often encounter a broad spectrum of allergic rhinitis (AR) and nonallergic rhinitis (NAR) patients, who can be variably classified based upon timing and severity of disease. Our understanding of the varied quality of life (QOL) impact in different classifications of rhinitis is limited. Thus a more comprehensive understanding of the impact of rhinitis upon our patients, as measured by both patient reported outcome measures (PROMs) and clinical physiologic measures, as well as unique factors associated with disease severity is needed. METHODS: A systematic search of databases was performed to identify AR and NAR studies reporting Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), total nasal symptom score (TNSS), or visual analogue scale (VAS) scores, and physiologic measures including peak nasal inspiratory flow (PNIF) and nasal airflow. Relationships between PROMs, physiologic measures, and associated factors (e.g., allergic status, disease duration) were assessed by weighted correlations and meta-regressions. RESULTS: A total of 171 studies reporting on 33,843 patients were included. Symptoms were more severe in AR than NAR on VAS (p < 0.001). Classification based upon Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines demonstrated differences in PROM severity. There was no significant correlation between PROMs and demographic factors, comorbidities, or physiologic measures. Meta-regression identified a correlation between worse RQLQ scores and shorter disease duration (r = -0.4, p < 0.001). CONCLUSION: Rhinitic patients have more severe impact upon QOL in the presence of allergy with variable impact upon specific symptom subdomains. PROMs do not correlate with common demographic factors, comorbidities, or physiologic measures of nasal airflow.

Rhinologic disease and its impact on sleep: a systematic review.

BACKGROUND: Rhinologic disease can be responsible for systemic symptoms affecting mood, cognition, and sleep. It is unclear whether sleep disturbance in specific rhinologic disorders (chronic rhinosinusitis [CRS], rhinitis, and nasal septal deviation [NSD]) is an obstructive phenomenon or due to other mechanisms. In this review we examine the impact of CRS, rhinitis, and NSD on objective and subjective sleep outcome metrics and draw comparisons to normal controls and patients with known obstructive sleep apnea (OSA). METHODS: A systematic review of 4 databases (PubMed, Scopus, Cochrane Library, and Web of Science) was performed. Studies reporting on objective (apnea-hypopnea index [AHI], respiratory disturbance index [RDI], oxygen nadir) and subjective (Epworth Sleepiness Scale [EpSS], Pittsburgh Sleep Quality Index [PSQI], Fatigue Severity Scale [FSS]) sleep parameters and disease-specific patient-reported outcome measures (PROMs; 22-item Sino-Nasal Outcome Test [SNOT-22], Rhinoconjunctivitis Quality of Life Questionnaire [RQLQ], Nasal Obstruction Symptom Evaluation [NOSE]) were included. RESULTS: The database search yielded 1414 unique articles, of which 103 were included for analysis. Baseline PROMs were at the high end of normal to abnormal for all 3 conditions: EpSS: CRS (9.8 ± 4.0), rhinitis (9.7 ± 4.3), and NSD (8.9 ± 4.6); and PSQI: CRS (11.0 ± 4.5), rhinitis (6.1 ± 3.7), and NSD (8.6 ± 3.5). Objective measures demonstrated a mild to moderate OSA in the studied diseases: AHI: CRS (10.4 ± 11.5), rhinitis (8.6 ± 8.8), and NSD (13.0 ± 6.9). There were significant differences when compared with reported norms in all measured outcomes (p < 0.001). CONCLUSION: Sleep quality is impacted by rhinologic (CRS, rhinitis, NSD) disease. There is likely a mild obstructive component contributing to poor sleep, but other contributing factors may be involved.

Kidney epithelial targeted mitochondrial transcription factor A deficiency results in progressive mitochondrial depletion associated with severe cystic disease.

Abnormal mitochondrial function is a well-recognized feature of acute and chronic kidney diseases. To gain insight into the role of mitochondria in kidney homeostasis and pathogenesis, we targeted mitochondrial transcription factor A (TFAM), a protein required for mitochondrial DNA replication and transcription that plays a critical part in the maintenance of mitochondrial mass and function. To examine the consequences of disrupted mitochondrial function in kidney epithelial cells, we inactivated TFAM in sine oculis-related homeobox 2-expressing kidney progenitor cells. TFAM deficiency resulted in significantly decreased mitochondrial gene expression, mitochondrial depletion, inhibition of nephron maturation and the development of severe postnatal cystic disease, which resulted in premature death. This was associated with abnormal mitochondrial morphology, a reduction in oxygen consumption and increased glycolytic flux. Furthermore, we found that TFAM expression was reduced in murine and human polycystic kidneys, which was accompanied by mitochondrial depletion. Thus, our data suggest that dysregulation of TFAM expression and mitochondrial depletion are molecular features of kidney cystic disease that may contribute to its pathogenesis.