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Introduction Alopecia areata (AA) is an autoimmune disease that causes scalp, face, and/or body hair loss. Recently, oral treatments with kinases inhibition became the first approved therapies for severe AA. An understanding of the use and effectiveness of traditional therapies in real-world treatment settings is needed to guide integration of novel therapies into the treatment paradigm. This study aimed to describe traditional treatment patterns, dermatologists’ reasons for therapy choice, and dermatologists’ satisfaction with disease control among patients with AA. Methods Data were drawn from the 2021–2022 Adelphi Real World AA Disease Specific Programme™, a cross-sectional survey of dermatologists and adult patients with AA, conducted in France, Germany, Italy, Spain, and the UK. For each patient, using data from patient consultation and medical records, dermatologists reported % scalp hair loss (SHL), characteristics of current and prior AA therapies, and satisfaction with disease control. Results Overall, 239 dermatologists provided data for 1720 patients with AA. Mean (SD) patient age was 35.8 (11.6) years, and 51% were male. Based on dermatologist perception, among patients with ≤ 10% SHL, 74% were experiencing mild AA, while ≥ 95% of patients with ≥ 50% SHL were experiencing severe/very severe AA. In patients with ≥ 50% SHL, the most common therapies received included systemic immunosuppressants (31%), topical corticosteroids (24%), and oral corticosteroids (24%). Among all patients who had switched therapies, 49%, 26%, and 24% switched because of worsening AA, lack of initial efficacy with prior treatment, and loss of response over time, respectively. Among those with SHL ≥ 50%, dermatologists reported satisfaction with current therapy in < 30% of patients. Conclusion Dermatologists reported low satisfaction with traditional AA therapies used in patients with extensive SHL, with some patients discontinuing treatment because of worsening disease. This suggests more effective treatments are needed for patients with severe AA.

Background The Severity of Alopecia Tool (SALT) is a clinician‐reported outcome measure of scalp hair loss in alopecia areata (AA). Objectives To characterise the magnitudes of change in SALT scores corresponding to meaningful treatment benefits from the patient's perspective. Methods Anchor‐based methods for the estimation of meaningful within‐patient change thresholds were applied to pooled data from a randomised, double‐blind trial of ritlecitinib. Anchors included a patient‐reported measure of change in AA severity, the Patient Global Impression of Change (PGI‐C) and three items comprising the Patient Satisfaction with Hair Growth (P‐Sat) questionnaire. After reviewing Pearson correlations between change‐from‐baseline SALT scores and each anchor to confirm adequate association, potential thresholds were computed as mean change‐from‐baseline SALT scores among patients who reported moderate improvement on the PGI‐C and/or moderate satisfaction on each of three P‐Sat items at week 24. Results Six hundred and fifty participants (86% adults, 14% adolescents) had mean (standard deviation) SALT scores of 90.6 (14.3) at baseline, suggesting a sample with primarily severe AA. Correlations between SALT change‐from‐baseline scores and the patient‐reported items supported their use as anchors. Estimates based on patients reporting moderate improvement in AA (n = 102) on the PGI‐C and those reporting moderate satisfaction on the P‐Sat item related to the amount of hair growth at week 24 (n = 122) were −42.2 (26.1) and −43.1 (26.8), respectively. Supportive estimates based on the remaining P‐Sat items were similar in magnitude. Conclusions Among patients with severe AA, SALT change‐from‐baseline scores of 42 or 43 represent meaningful improvements. While the achievement of low SALT scores of ≤10–≤20 have been used to characterise efficacy in clinical trials, the amount of change required to meet this endpoint far exceeds the estimates in this study. The treatment goals of individual patients must be considered when evaluating benefit in both clinical trials and clinical practice. Applying anchor‐based methods, we used pooled data from a randomised, double‐blind trial of ritlecitinib to estimate meaningful within‐patient change thresholds for the Severity of Alopecia Tool (SALT), a clinician‐reported measure of scalp hair loss in alopecia areata (AA). Based on patients reporting moderate improvement in AA on the Patient Global Impression of Change and reporting moderate satisfaction on the Patient Satisfaction with Hair Growth at Week 24, estimates of meaningful SALT change from baseline scores were 42 and 43, respectively.

Reversible axonal swelling and brainstem auditory evoked potential (BAEP) changes were observed in standard chronic (9‐month) toxicology studies in dogs treated with ritlecitinib, an oral Janus kinase 3/tyrosine kinase expressed in hepatocellular carcinoma family kinase inhibitor, at exposures higher than the approved 50‐mg human dose. To evaluate the clinical relevance of the dog toxicity finding, this phase 2a, double‐blind study assessed BAEP changes and intraepidermal nerve fiber (IENF) histology in adults with alopecia areata treated with ritlecitinib. Patients were randomized to receive oral ritlecitinib 50 mg once daily (QD) with a 4‐week loading dose of 200 mg QD or placebo for 9 months (placebo‐controlled phase); they then entered the active‐therapy extension and received ritlecitinib 50 mg QD (with a 4‐week loading dose of 200 mg in patients switching from placebo). Among the 71 patients, no notable mean differences in change from baseline (CFB) in Waves I–V interwave latency (primary outcome) or Wave V amplitude on BAEP at a stimulus intensity of 80 dB nHL were observed in the ritlecitinib or placebo group at Month 9, with no notable differences in interwave latency or Wave V amplitude between groups. The CFB in mean or median IENF density and in percentage of IENFs with axonal swellings was minimal and similar between groups at Month 9. Ritlecitinib treatment was also not associated with an imbalanced incidence of neurological and audiological adverse events. These results provide evidence that the BAEP and axonal swelling finding in dogs are not clinically relevant in humans. Results of this placebo‐controlled study, which assessed the neurological and neuroaudiological effects of ritlecitinib in adults with alopecia areata, provide evidence that the brainstem auditory evoked potential (BAEP) changes and axonal swelling finding in standard chronic toxicology studies in dogs are not clinically relevant in humans.

Sentinel lymph node biopsy (SLNB) allows early detection of metastases, thereby enabling early treatment in melanoma patients likely to benefit from adjuvant therapies. This prospective study analyzes the possible benefits of additional ultrasound (US) and fine needle aspiration cytology (FNAC) of sentinel nodes (SN) prior to SLNB. Over a 2-year period 127 melanoma patients with 151 SN were scheduled for SLNB. All SN were initially identified with lymphoscintigraphy, then identified and evaluated by US and the cells aspirated for cytology (FNAC). US findings and FNAC results were compared to surgical findings. Of 127 patients, 114 had one SN each, 12 had two, and one had three. In vivo US achieved a sensitivity of 79% (95% CI: 62-91%) and a specificity of 72% (95% CI: 62-81%). FNAC showed a sensitivity of 59% (95% CI: 41-76%) and a specificity of 100% (95% CI: 95-100%). The combination of these two in vivo methods achieved an overall sensitivity of 82% (95% CI: 65-93%) and an overall specificity of 72% [95% CI: 62-81%]. Combined US and FNAC provides important information prior to SLNB in that both procedures identify metastases in the lymph nodes (sensitivity > 80%). Patients with positive FNAC may proceed directly to complete lymph node dissection (cLND) instead of having initial SLNB. Thus, combined US and FNAC may prevent unnecessary anesthesia and surgical management as well reduce costs. In our study 16% (19/121) fewer SLNB procedures were carried out, subsequently replaced by cLND. For patients with a negative combination of in vivo US and FNAC, SLNB remains the best diagnostic option.

Ultrasound-guided fine-needle aspiration cytology is an evolving method for quick diagnosis of the presence or absence of tumor in lymph nodes in malignant melanoma patients. New criteria for suspicion have greatly improved sensitivity and thus the clinical utility of ultrasound-guided fine-needle aspiration cytology. An earlier diagnosis of the presence of metastasis may lead to earlier surgical and systemic treatments and therefore an improvement of outcome in terms of relapse-free and even overall survival.

Specialized medical centers perform high-resolution ultrasound of lymph nodes in melanoma patients to detect metastases early. Ultrasound represents a highly effective method for the discrimination of lymph node and soft-tissue metastases from other space-occupying lesions. Frequent follow-up examinations with ultrasound provide early detection of tumor recurrences and seem to lead to a prolonged overall survival. The ultrasound findings are validated by fine-needle aspiration cytology. Depicted and verified metastases should be removed as soon as possible. The authors recommend the performance of ultrasound before every sentinel lymph node dissection to avoid unnecessary operations.

We present a systematic treatment of the initial conditions and evolution of cosmological perturbations in a universe containing photons, baryons, neutrinos, cold dark matter, and a scalar quintessence field. By formulating the evolution in terms of a differential equation involving a matrix acting on a vector comprised of the perturbation variables, we can use the familiar language of eigenvalues and eigenvectors. As the largest eigenvalue of the evolution matrix is fourfold degenerate, it follows that there are four dominant modes with non-diverging gravitational potential at early times, corresponding to adiabatic, cold dark matter isocurvature, baryon isocurvature and neutrino isocurvature perturbations. We conclude that quintessence does not lead to an additional independent mode.

We determine the influence of a variation of the fundamental ``constants'' on the predicted helium abundance in Big Bang Nucleosynthesis. The analytic estimate is performed in two parts: the first step determines the dependence of the helium abundance on the nuclear physics parameters, while the second step relates those parameters to the fundamental couplings of particle physics. This procedure can incorporate in a flexible way the time variation of several couplings within a grand unified theory while keeping the nuclear physics computation separate from any model-dependent assumptions.

We present a systematic treatment of the initial conditions and evolution of cosmological perturbations in a universe containing photons, baryons, neutrinos, cold dark matter, and a scalar quintessence field. By formulating the evolution in terms of a differential equation involving a matrix acting on a vector comprised of the perturbation variables, we can use the familiar language of eigenvalues and eigenvectors. As the largest eigenvalue of the evolution matrix is fourfold degenerate, it follows that there are four dominant modes with non-diverging gravitational potential at early times, corresponding to adiabatic, cold dark matter isocurvature, baryon isocurvature and neutrino isocurvature perturbations. We conclude that quintessence does not lead to an additional independent mode.