Efficacy and safety of deuruxolitinib, an oral selective Janus kinase inhibitor, in adults with alopecia areata: Results from the Phase 3 randomized, controlled trial (THRIVE-AA1).

BACKGROUND: Alopecia areata (AA) is a hair loss disorder that can seriously impact quality of life. Janus kinase (JAK) inhibitors, including deuruxolitinib, have previously demonstrated significant hair regrowth in AA. OBJECTIVE: The Phase 3 THRIVE-AA1 randomized, double-blinded, placebo-controlled trial (NCT04518995) evaluated safety and efficacy of the oral JAK1/JAK2 inhibitor deuruxolitinib in adult patients with AA. METHODS: Patients aged 18-65 years with ≥50% hair loss were randomized to deuruxolitinib 8 mg BID, deuruxolitinib 12 mg BID, or placebo for 24 weeks. The primary endpoint was percentage of patients achieving Severity of Alopecia Tool (SALT) score ≤20. A key secondary endpoint was percentage of satisfaction of hair patient-reported outcome (SPRO) responders. RESULTS: Significantly higher proportions of patients taking deuruxolitinib met the primary endpoint (8 mg 29.6%; 12 mg 41.5% versus placebo 0.8%). Both deuruxolitinib doses achieved significant improvements in all secondary endpoints versus placebo, including SPRO (8 mg 42.1%; 12 mg 53.0% versus placebo 4.7%). Most treatment-emergent adverse events were mild or moderate, consistent with other oral JAK inhibitors. LIMITATIONS: Further studies are required to understand longer-term safety, efficacy, and impact of treatment cessation. CONCLUSION: Both doses of deuruxolitinib were effective for hair regrowth. Patient satisfaction aligned with hair growth.

Lax Uterosacral Ligament and Urge Urinary Incontinence: MRI Findings in Symptomatic Patients Versus Healthy Volunteers.

INTRODUCTION AND HYPOTHESIS: The objective was to explore the association between urge urinary incontinence (UUI) and lax uterosacral ligaments (USL) using MRI. METHODS: Sixty-seven female participants were recruited prospectively: 41 continent volunteers (control group) and 26 patients with UUI. Static proton density- and T2-weighted turbo spin echo sequences of MR images were used. A radiologist employed a standardized grid system to record structural observations of the USLs on sequentially numbered axial MR images and then applied a four-point grading scale to assess ligament visibility. MR images were interpreted by a radiologist and a urologist, and then validated by an expert radiologist. RESULTS: The comparison between the mean length of uterosacral ligaments in the control and UUI groups was highly statistically significant (p < 0.001). The mean length of the right USL was 38 ± 11 mm, and the left USL was 35 ± 12 mm in the UUI group. In the control group, the mean length of the USL was 22 ± 9 mm on the right side and 18 ± 9 mm on the left side, along their craniocaudal extent. The highest inter-observer agreement was on the level of origin and insertion (image numbers), whereas the lowest agreement was on the anatomical site of origin and insertion of the USL in both the control and UUI groups. CONCLUSIONS: The average length of USLs in patients with UUI is significantly longer than that in healthy continent women, indicating laxity. Our findings support the relationship between the laxity of the USL and UUI symptoms and have therapeutic implications.

The burden of alopecia areata: A scoping review focusing on quality of life, mental health and work productivity.

Alopecia areata (AA) is a common inflammatory autoimmune disease of the hair which can have a significant negative impact on quality of life (QoL), mental health and productivity. The aim of this scoping review is to elucidate the burden of AA focusing on these three realms. Inclusion criteria included all original manuscripts with no restriction on study type or statistical method written in English (or having an English abstract). For QoL 40 articles were included, 85 for psychiatric comorbidities, and 9 for work/school absenteeism/presenteeism mostly consisting of cross-sectional and observational cohort studies. QoL impairment was detected in over 75% of patients and up to one-third reported extremely severe QoL impairments. Specific QoL dimensions with the greatest impact were embarrassment, social functioning, as well as shopping and/or housework. Cross-sectional studies assessing the psychological burden of adult patients with AA found that the presence of signs of anxiety and/or depression ranged from 30% to 68% and affected all age groups. Rates of work absenteeism and unemployment were significantly higher in AA patients compared to healthy controls. Up to 62% reported making major life decisions including relationships, education and career based on their AA. Additionally, the extensive camouflage techniques and time lost from work led to a strong financial burden for patients and the numerous physician visits added to the healthcare costs. The overall impact of AA stretches much further than simply being an aesthetic concern and can negatively impact every part of an individual's life. An individualized approach and effective treatments will help reduce the psychosocial consequences and distress and return patients to their normal state of health.

Systematic Review on the Efficacy and Safety of Oral Janus Kinase Inhibitors for the Treatment of Atopic Dermatitis.

Background: Atopic dermatitis is a chronic, relapsing and remitting disease that can be difficult to treat despite a recently approved biologic therapy targeting IL-4/IL-13 receptor. Oral janus kinase inhibitors (JAKi) represent a novel therapeutic class of targeted therapy to treat moderate-to-severe atopic dermatitis (AD). Objective: To review the efficacy, safety, and pharmacokinetic characteristics of oral JAKi in the treatment of AD. Methods: A PRISMA systematic review was conducted using MEDLINE, EMBASE (Ovid), and PubMed databases for studies assessing the efficacy, safety, and/or pharmacokinetic properties of oral forms of JAKi in the treatment of AD in pediatric or adult populations from inception to June 2021. Results: 496 papers were reviewed. Of 28 articles that underwent full text screening, 11 met our inclusion criteria for final qualitative review. Four studies examined abrocitinib; three studies examined baricitinib; three examined upadacitinib and one examined gusacitinib (ASN002). Significant clinical efficacy and a reassuring safety profile was reported for all JAKi agents reviewed. Rapid symptom control was reported for abrocitinib, baricitinib and upadacitinib. Limitations: Given the relatively limited evidence for each JAKi and the differences in patient eligibility criteria between studies, the data was not deemed suitable for a meta-analysis at this time. Conclusion: Given their ability to achieve rapid symptom control with a reassuring safety profile, we recommend considering the use of JAKi as a reliable systemic treatment option for adult patients with moderate-to-severe AD, who are unresponsive to topical or skin directed treatments.

The diagnostic utility of combined diffusion-weighted imaging and conventional magnetic resonance imaging for detection and localization of non palpable undescended testes.

INTRODUCTION: We aimed to evaluate the diagnostic performance of combined diffusion weighted imaging (DWI) and conventional magnetic resonance imaging (MRI), including fat-suppression T2WI for identification and localization of non palpable undescended testes (UDTs). METHODS: This prospective study included 40 consecutive patients, with 47 non-palpable undescended testes (unilateral in 33 cases and bilateral in seven cases). Their age ranged from 5 months to 18 years, mean = 7.5 ± 5.9 years. MRI examinations included T1WI, T2WI, fat-suppression T2WI and DWI at b value of 50, 400 and 800 s/mm(2) . All patients underwent laparoscopic exploration. RESULTS: According to the laparoscopy findings, the final diagnoses of the location of UDTs were: intra-canalicular (n = 18, 38%), low intra-abdominal (n = 6, 13%), high intra-abdominal (n = 5, 11%). Absent or vanishing testes were detected in 18 cases (38%). The diagnostic accuracy, sensitivity, specificity of combined DWI and conventional MRI were 95.7%, 93.5% and 100% respectively. CONCLUSION: Combined DWI and MRI showed a greater performance compared to conventional MRI alone for identification of non-palpable UDTs. Based on our findings, we can obviate the need for diagnostic laparoscopy in patients who had preoperative detection of inguinal testes or nubbins. However, laparoscopy is still needed to confirm an absent rather than undetected non-viable abdominal testes.

Detection of Barrett's esophagus after endoscopic healing of erosive esophagitis.

BACKGROUND: The presence of erosive esophagitis (EE) in patients presenting for upper endoscopy may prevent the detection of underlying Barrett's esophagus (BE) in the distal esophagus. AIM: To prospectively determine the proportion of patients detected with BE upon repeat endoscopy after healing of EE. METHODS: Patients with endoscopically confirmed EE without BE were treated with standard doses of acid suppression therapy and a repeat endoscopy was performed to assess the presence of BE. If columnar mucosa was visualized in the distal esophagus, targeted biopsies were obtained and all biopsies were evaluated for the presence of intestinal metaplasia. BE was defined as columnar mucosa in the distal esophagus with intestinal metaplasia on biopsy. RESULTS: A total of 172 patients with reflux symptoms were diagnosed with EE without BE on initial endoscopy. They were treated with standard doses of proton pump inhibitor therapy, and after a mean duration of 11 wk (range 8-16 wk), a repeat endoscopy was performed to confirm healing of EE and to document the presence of BE. On repeat endoscopy, EE was completely healed in 116 patients (67%), and of those, BE was suspected in 32 patients (i.e., columnar-lined distal esophagus) and was confirmed in 16 patients (13.8%). In the 56 patients with persistent EE on repeat endoscopy, columnar mucosa in areas of previously healed esophagitis was visualized in 8 and confirmed in 5 patients (8.9% of nonhealed cases). Overall, 21 (12%) patients were confirmed with BE on repeat endoscopy; all men, mean age 61 yr with a median BE length of 0.5 cm (range 0.5-5 cm, interquartile range 0.5 cm). The majority of these patients (N = 19) had short segment Barrett's esophagus (SSBE) (i.e., length <3 cm). CONCLUSIONS: In patients with EE undergoing treatment with acid suppressive therapy, BE (mainly SSBE) is detected in approximately 12% of patients on repeat endoscopy. Patients with reflux symptoms undergoing endoscopy for the detection of BE (i.e., screening) should be treated with acid suppressive therapy prior to endoscopy to enhance the yield of BE. Alternatively, if the goal is to document BE and if EE is found at the initial endoscopy, then repeat endoscopy may be considered after acid suppressive therapy.

Angiolymphoid hyperplasia with eosinophilia: a classic clinical presentation with histologic features of angiosarcoma.

BACKGROUND: Angiolymphoid hyperplasia with eosinophilia (ALHE) is a rare disease manifested by the proliferation of morphologically distinct endothelial cells. OBJECTIVE: To illustrate by a case report the clinical and varied histopathologic findings of ALHE. METHODS: A 29-year-old woman presented with a clinical picture of ALHE but had several histologic features of angiosarcoma. RESULTS: Management of this patient included repeat biopsies of the lesions, excision of the involved areas, careful histologic examination of the entire specimen, and appropriate follow-up. CONCLUSION: ALHE may present with various histologic features. Knowledge of the spectrum of benign and malignant vascular neoplasms helps manage these challenging cases.