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The Intersection of Sleep and Hair Loss: A Systematic Review
No full textSleep disturbance is increasingly recognized as a modifier of dermatologic disease, yet its role in hair loss remains underexplored. Hair loss disorders, including alopecia areata (AA), androgenetic alopecia (AGA), telogen effluvium (TE), and scarring alopecias, carry substantial psychosocial burden and involve neuroendocrine and immune pathways sensitive to sleep quality.
To systematically evaluate associations between sleep disturbances and hair loss across major hair loss subtypes, define shared and subtype-specific mechanisms, and highlight insights relevant to counseling, symptom monitoring, and dermatologic management.
A Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA)-guided systematic review of PubMed and Scopus identified 291 studies examining sleep disturbances in hair loss. After duplicate removal and screening by two independent reviewers, 29 studies were included. Extracted data included study design, level of evidence, hair loss subtype, sleep measures, mechanisms, and psychosocial correlates.
Overall evidence quality was low to moderate (1 level II, 11 level III, 14 level IV, and 3 level V), with cross-sectional studies predominating (n = 15). AA was most represented (n = 14), followed by AGA (n = 11), TE (n = 3), lichen planopilaris (LPP) (n = 1), and traction alopecia (n = 1). Sleep disturbance was consistently elevated across AA, AGA, TE, and LPP populations, commonly assessed by the PSQI. Mechanistic themes varied by subtype: cytokine activation, hypothalamic-pituitary-adrenal axis dysregulation, and altered clock-genes in AA; circadian misalignment, obstructive sleep apnea-related hypoxia, and hormonal imbalance in AGA; neurogenic inflammation and substance-P pathways in TE; and chronic pruritus and pain in LPP. Psychosocial distress amplified sleep disruption in most subtypes.
Across hair loss disorders, sleep disturbance emerges as a biologically plausible and clinically relevant contributor to disease burden. Although most evidence is observational, converging mechanistic and psychosocial data support a bidirectional relationship between sleep quality and hair loss. Incorporating brief sleep assessments into hair loss care and considering sleep-targeted interventions may improve disease stability and patient well-being. Longitudinal and mechanistic studies are needed to clarify causality and identify therapeutic targets
392. Favorable Adherence and Safety of Twice-Yearly Subcutaneous Lenacapavir for PrEP Among PURPOSE 2 Participants Who Used Substances
No full textBackground Cisgender men and gender-diverse individuals with a high likelihood of HIV acquisition are disproportionately affected by substance use, which can affect HIV pre-exposure prophylaxis (PrEP) adherence. Twice-yearly subcutaneous (SC) lenacapavir (LEN) showed high efficacy and safety for PrEP in PURPOSE 2 (NCT04925752). We investigated the impact of substance use on LEN adherence and safety in PURPOSE 2. As LEN is an inhibitor of CYP3A, an enzyme involved in fentanyl metabolism, we developed a physiologically based pharmacokinetic (PBPK) model to evaluate this potential drug–drug interaction. Methods Substance use was defined as any self-reported drug use, stimulant use, and opioid use in the 12 weeks prior to baseline, and/or binge drinking (≥ 6 drinks on 1 occasion). Adherence (on-time injections) and safety (adverse events [AEs]) through the primary analysis were compared across participants reporting different types of substance use and those reporting no substance use. Prior in vitro, clinical, and published fentanyl PK data were used to develop a PBPK model to evaluate the impact of LEN on fentanyl concentrations. Results Of 2183 participants randomized to LEN, 767/2061 (37.2%) reported any drug use, 17/2092 (0.8%) injected drugs, 409/2058 (19.9%) used stimulants, 33/2086 (1.6%) used opioids, and 841/2074 (40.5%) had monthly or more binge-drinking episodes at baseline. LEN adherence was high and comparable across substance use types and to participants who did not report substance use (Figure). No substance use–related overdoses or study drug-related serious AEs were reported, and overall incidence of AEs was similar across groups (Table). The most common AEs (excluding injection-site reactions) were gonococcal, chlamydia, and upper respiratory tract infections. PBPK modeling indicated no clinically significant elevations in fentanyl PK with concomitant LEN. Conclusion In PURPOSE 2, a population with high rates of substance use, there was high adherence to twice-yearly SC LEN for PrEP and a favorable safety profile among participants who used drugs and alcohol. There were no substance use–related overdoses and no clinically significant impact of LEN on fentanyl concentrations was found. These data support twice-yearly SC LEN to prevent HIV in people who use substances. Disclosures Allison Agwu, MD, ScM, Gilead Biosciences: Grant/Research Support|Gilead Biosciences: Site PI of multi-site project & investigator-initiated grant (funds to institution) Jill Blumenthal, MD MAS, Clinical Care Options: speaking fees|Gilead Biosciences: Advisor/Consultant|Gilead Biosciences: Grant/Research Suppor
Recurrent Respiratory Papillomatosis Foundation Position Statement on the Management of Adults With RRP
No full textWith regulatory approval of HPV-specific immunotherapy for recurrent respiratory papillomatosis (RRP) and growing experience with systemic bevacizumab, a management algorithm incorporating these medical treatments is warranted.
RRP Foundation (RRPF) Key Opinion Leaders offer a proposed management algorithm for adults with RRP considering published literature and commercial drug availability.
Preventative HPV vaccination should be considered for all patients. Determination of HPV type and pulmonary imaging are important for contemporary RRP patient care and assist in decision making. Risks and benefits of papilloma debulking as needed versus medical management of RRP must be deliberated on a patient case-by-case basis. HPV-specific immunotherapy that induces an HPV-specific T cell response to target the underlying HPV infection that is the cause of RRP is safe, offers the possibility of durable disease control following a short treatment course and is the recommended first-line medical treatment for patients who wish to avoid the risks of repeat procedural management. Papilloma disease control with systemic bevacizumab, which carries defined risks and must be continued for clinical benefit is the recommended second-line medical treatment for patients who do not achieve a complete response with immunotherapy and wish to continue medical management. For patients who elect to be treated with debulking procedures as needed, use of locally-administered adjuvant should be considered.
This proposed management algorithm from the RRPF serves as a contemporary resource and information guide for adult patients with RRP and their physicians considering treatment options
Acquired Progressive Kinking of the Hair: A Narrative Review of the Androgen‐Dependent Phenotype
No full textAcquired progressive kinking of the hair (APKH) is an underrecognized hair disorder characterized by a gradual change in hair texture, often manifesting as increased curliness, frizziness, and darkening of the shafts. While various systemic triggers and congenital conditions can induce similar phenotypes, a subset of cases—particularly those involving the frontal and temporal scalp in young males—appears to be linked to androgen‐mediated mechanisms. This narrative review focuses on the androgen‐dependent phenotype of APKH, integrating clinical, trichoscopic, and histopathological findings and presenting a representative case. We also propose a conceptual framework for distinguishing between androgen‐dependent and non–androgen‐dependent subtypes. A detailed analysis of all published cases meeting criteria for androgen‐sensitive APKH is provided, highlighting patterns of progression, diagnostic clues, and therapeutic implications. Recognizing this presentation as a potential early manifestation of androgenetic alopecia may inform clinical decisions and prompt timely intervention
A phase 1 trial of the oncolytic virus SVV-001 in combination with nivolumab and ipilimumab in patients with poorly differentiated neuroendocrine carcinomas or well-differentiated grade 3 neuroendocrine tumors
No full textTPS650 Background: High-grade neuroendocrine neoplasms (NENs), including poorly differentiated neuroendocrine carcinomas (NECs) and well-differentiated grade 3 neuroendocrine tumors (NETs), are aggressive malignancies with limited effective treatment options. Immune checkpoint inhibitors (ICIs) have demonstrated limited clinical activity in these tumors. Seneca Valley Virus (SVV-001) is a novel oncolytic RNA virus that has shown synergistic activity with ICIs in preclinical models. Additionally, SVV-001 has been observed to reverse checkpoint inhibitor resistance in vivo, supporting its evaluation in combination with nivolumab and ipilimumab. Methods: This is an investigator-initiated, phase 1, dose-escalation and cohort-expansion study evaluating intratumoral SVV-001 in combination with nivolumab and ipilimumab in patients with histologically confirmed poorly differentiated NEC or well-differentiated grade 3 NET. The trial was activated in March 2025, with patient enrollment currently ongoing and a target of up to 36 patients. A standard 3+3 dose-escalation design is being employed to determine the recommended phase 2 dose (RP2D). Following dose escalation, an expansion cohort will further evaluate safety and preliminary signals of activity. Tumor endothelial marker 8 (TEM8), a potential biomarker of SVV-001 sensitivity, will be assessed as part of correlative studies. Clinical trial information: NCT06889493
Impacts of Distress Intolerance and Anxiety Sensitivity on the Maintenance and Treatment of Youth Misophonia
No full textThis study was registered on ClinicalTrials. gov (NCT04365543)
An Investigation of Inhibitory Control as a Mechanism Differentiating Tonic and Phasic Irritability
No full textPhasic and tonic irritability are highly correlated clinical constructs yet differentially associated with developmental trajectories and treatment response. However, limited research has identified their shared and unique underlying behavioral mechanisms. In a sample of youths enriched for irritability (N = 141, age range 7-18, age M[SD] = 12.60[2.54], 48.23% female), we investigated whether inhibitory control is differentially associated with phasic versus tonic irritability. Replicating prior work, tonic and phasic irritability were estimated via independent confirmatory factor analyses (CFAs) using items and/or subscales from multi-informant questionnaires. A latent factor of inhibitory control was extracted from four behavioral tasks. Initial multiple linear regression analysis found that phasic, not tonic, irritability was significantly associated with impaired inhibitory control. However, results were no longer significant after accounting for shared associations with age. In addition, when adding commonly co-occurring symptoms such as attention-deficit/hyperactivity disorder (ADHD) symptoms and oppositionality, age and ADHD were significant predictors of inhibitory control, but phasic irritability was not. Results suggest that inhibitory control alone may not be a salient mechanism for disambiguating phasic and tonic irritability. Future work leveraging longitudinal methods and consideration of other potential contextual factors is needed
Influence of Intraocular Pressure on Clinical Decision-Making in Glaucoma Management
No full textUnderstanding of intraocular pressure (IOP) as a continuous risk factor for glaucoma has evolved over time, and IOP reduction is widely acknowledged as the mainstay of treatment. However, the impact of specific IOP levels on clinical decision-making remains an underexplored topic.
To assess how IOP levels influence the decision to initiate or escalate glaucoma therapy in clinical practice.
In this retrospective, multicenter cohort study, the Sight Outcomes Research Collaborative (SOURCE) ophthalmology data repository was used to identify clinic encounters between October 2009 and January 2022 for patients with glaucoma with IOPs ranging from 12 mm Hg to 25 mm Hg. Data analysis was performed from July 2024 to September 2025.
The primary outcome was whether IOP-lowering therapy was initiated or escalated after each clinic encounter, defined as a new prescription for IOP-lowering medication within 1 week of the encounter, laser treatment within 4 weeks, or glaucoma surgery within 8 weeks. The rate of treatment initiation at different IOP levels was measured, and then mixed-effects logistic regression was used to model the odds of treatment initiation at specific indicator IOP levels.
This analysis included 1 866 801 clinic encounters from 184 504 eyes of 94 232 unique patients across 7 sites in SOURCE. Mean (SD) patient age was 69.5 (10.8) years, and of the total clinic encounters, 1 084 827 (58.1%) included female patients. The rate of IOP-lowering treatment increased with higher IOP levels, with the largest acceleration in treatment rate at IOPs of 22 mm Hg or higher. With mixed-effects logistic regression modeling, an indicator IOP of 22 mm Hg had a greater effect on treatment initiation (odds ratio, 1.11; 95% CI, 1.08-1.14) compared with lower indicator IOPs.
In this cohort study, while clinicians seem to generally use IOP as a continuous risk factor in their treatment patterns, with higher rates of glaucoma therapy at increasing IOP levels, these findings suggest that the historical IOP cutoff of 22 mm Hg may still influence clinician decision-making in glaucoma management. Improved clinical decision support may be useful to assist clinicians with using IOP as a continuous risk factor in their decision-making
Revisiting the INSPIRE trial: antibody profiling reveals high prevalence of occult autoimmunity
No full textIn the INSPIRE trial, patients diagnosed with Idiopathic Pulmonary Fibrosis (IPF) failed to demonstrate improved survival after treatment with IFN-gamma-1β. This outcome became the impetus to develop more personalized approaches to the diagnosis, classification, and management of pulmonary fibrosis.
The present study was designed to assess autoantibody profiles in a randomly selected group of INSPIRE trial participants in order to better define IPF on a molecular diagnostic level and define subsets with potentially different underlying disease processes.
We performed conventional, gel-based protein and RNA immunoprecipitation (IP) on 483 plasma specimens derived from patients enrolled in both the treatment and placebo arms of INSPIRE. Tandem immunoprecipitation and mass spectrometry proteomics (IP-to-MS) of selected specimens was used to confirm conventional IP interpretation and to identify unknown autoantigens.
Based on conventional IP approaches, approximately 30% of trial participants had evidence of autoimmune disease-specific autoantibodies and another ~ 10% had evidence of autoantibodies of unknown specificity. IP-to-MS revealed additional autoantigens, including Annexin 11.
IP analyses demonstrated an unexpectedly high prevalence of autoantibodies potentially indicative of underlying connective tissue disease-associated ILD, underscoring the importance of classification schemes incorporating unbiased autoantibody profiling