Efficacy and safety of ritlecitinib in adults and adolescents with alopecia areata: a randomised, double-blind, multicentre, phase 2b-3 trial.

BACKGROUND: Alopecia areata is characterised by non-scarring loss of scalp, face, or body hair. We investigated the efficacy and safety of ritlecitinib, an oral, selective dual JAK3/TEC family kinase inhibitor, in patients with alopecia areata. METHODS: In this randomised, double-blind, multicentre, phase 2b-3 trial done at 118 sites in 18 countries, patients aged 12 years and older with alopecia areata and at least 50% scalp hair loss were randomly assigned to oral ritlecitinib or placebo once-daily for 24 weeks, with or without a 4-week loading dose (50 mg, 30 mg, 10 mg, 200 mg loading dose followed by 50 mg, or 200 mg loading dose followed by 30 mg), followed by a 24-week extension period during which ritlecitinib groups continued their assigned doses and patients initially assigned to placebo switched to ritlecitinib 50 mg or 200 mg loading dose followed by 50 mg. Randomisation was done by use of an interactive response system and was stratified by baseline disease severity and age. The sponsor, patients, and investigators were masked to treatment, and all patients received the same number of tablets to maintain masking. The primary endpoint was Severity of Alopecia Tool (SALT) score 20 or less at week 24. The primary endpoint was assessed in all assigned patients, regardless of whether they received treatment. This study was registered with ClinicalTrials.gov, NCT03732807. FINDINGS: Between Dec 3, 2018, and June 24, 2021, 1097 patients were screened and 718 were randomly assigned to receive ritlecitinib 200 mg + 50 mg (n=132), 200 mg + 30 mg (n=130), 50 mg (n=130), 30 mg (n=132), 10 mg (n=63), placebo to 50 mg (n=66), or placebo to 200 mg + 50 mg (n=65). 446 (62%) of 718 patients were female and 272 (38%) were male. 488 (68%) were White, 186 (26%) were Asian, and 27 (4%) were Black or African American. Of 718 patients randomly assigned, 104 patients discontinued treatment (34 withdrew, 19 adverse events [AEs], 12 physician decision, 12 lack of efficacy, 13 lost to follow up, five rolled over to long-term study transfer, four pregnancies, two protocol deviations, one declined to attend follow-up due to COVID-19, one attended last visit very late due to COVID-19, and one non-compliance). At week 24, 38 (31%) of 124 patients in the ritlecitinib 200 mg + 50 mg group, 27 (22%) of 121 patients in the 200 mg + 30 mg group, 29 (23%) of 124 patients in the 50 mg group, 17 (14%) of 119 patients in the 30 mg group, and two (2%) of 130 patients in the placebo group had a response based on SALT score 20 or less. The difference in response rate based on SALT score 20 or less between the placebo and the ritlecitinib 200 mg + 50 mg group was 29·1% (95% CI 21·2-37·9; p<0·0001), 20·8% (13·7-29·2; p<0·0001) for the 200 mg + 30 mg group, 21·9% (14·7-30·2; p<0·0001) for the 50 mg group, and 12·8% (6·7-20·4; p=0·0002) for the 30 mg group. Up to week 48 and including the follow-up period, AEs had been reported in 108 (82%) of 131 patients in the ritlecitinib 200 mg + 50 mg group, 105 (81%) of 129 patients in the 200 mg + 30 mg group, 110 (85%) of 130 patients in the 50 mg group, 106 (80%) of 132 patients in the 30 mg group, 47 (76%) of 62 patients in the 10 mg group, 54 (83%) of 65 patients placebo to ritlecitinib 200 mg + 50 mg in the extension period, and 57 (86%) of 66 patients in the placebo to 50 mg group. The incidence of each AE was similar between groups, and there were no deaths. INTERPRETATION: Ritlecitinib was effective and well tolerated in patients aged 12 years and older with alopecia areata. Ritlecitinib might be a suitable treatment option for alopecia areata in patients who are candidates for systemic therapy. FUNDING: Pfizer.

Patient-Reported Satisfaction With Hair Regrowth in a Study of Ritlecitinib in Alopecia Areata: Results From ALLEGRO-2b/3.

INTRODUCTION: Patients with alopecia areata (AA) report high levels of dissatisfaction with commonly used treatments. Patient-reported outcomes are essential to understanding patients' experiences with AA treatments. The objective of this study was to evaluate patient-reported satisfaction with hair growth among patients with AA receiving ritlecitinib or placebo and the correlation between clinician-assessed efficacy and patient-reported satisfaction. METHODS: In the ALLEGRO-2b/3 (NCT03732807) trial, patients with AA and ≥50% scalp hair loss were randomized to daily ritlecitinib or placebo for 24 weeks, with a 24-week extension of continued ritlecitinib or switch from placebo to ritlecitinib. The Patient Satisfaction with Hair Growth (P-Sat) measure evaluated patients' satisfaction with hair growth in 3 domains: amount, quality, and overall satisfaction with hair growth. The pre-specified analysis evaluated the proportion of patients who were slightly, moderately, or very satisfied with hair growth. Several post-hoc analyses assessed the proportion of patients who were moderately/very satisfied and moderately/very dissatisfied and calculated polyserial correlations between change from baseline (CFB) in Severity of Alopecia Tool (SALT) and P-Sat scores at Weeks 24 and 48. RESULTS: At Week 24, the proportion of patients (N=718) reporting satisfaction (slightly, moderately, or very satisfied) overall with their hair growth ranged from 36.4% in the ritlecitinib 10-mg group (evaluated for dose ranging only) to 67.5% in the 200/50-mg group vs 22.6% in the placebo groups. In patients randomized to ritlecitinib, the proportion who were satisfied increased or was maintained at Week 48. A substantially greater proportion of placebo patients who switched to ritlecitinib reported satisfaction at Week 48 than at Week 24. Similar results were observed for patient satisfaction with the amount and quality of hair growth. In the post hoc analyses defining satisfaction as moderately/very satisfied and dissatisfaction as moderately/very dissatisfied, the benefit of ritlecitinib was also observed. All P-Sat domain scores strongly correlated with CFB-SALT scores at Weeks 24 (range 0.73-0.76; P<0.05) and 48 (0.74-0.77; P<0.05). CONCLUSIONS: Patients receiving active ritlecitinib doses reported favorable results vs placebo in satisfaction with hair growth up to Week 48. High concordance was observed between improvement in scalp hair growth evaluated by clinicians and patient-reported satisfaction. TRIAL REGISTRATION: Clinicaltrials.gov NCT0373280.

Allergen desensitization reduces the severity of relapsed alopecia areata in dust-mite allergic patients.

Atopy may be a facilitating factor in some alopecia areata (AA) patients with early disease onset and more severe/extensive AA. The underlying immune mechanisms are unknown, but allergen responses may support a pro-inflammatory environment that indirectly promotes AA. To investigate the long-term effect of allergen immunotherapy (AIT) against house dust mite (HDM) allergy on disease severity and prognosis for AA patients. An observational comparative effectiveness study was conducted on 69 AA patients with HDM allergy. 34 patients received conventional/traditional AA treatment (TrAA) plus AIT (AIT-TrAA), and 35 patients received TrAA alone. Serum total immunoglobulin E (tIgE), HDM specific IgE (sIgE), HDM specific IgG4 (sIgG4) and cytokines (IL-4, IL-5, IL-10, IL-12, IL-13, IL-33, IFNγ) were quantified in these patients, together with 58 non-allergic AA patients and 40 healthy controls. At the end of the 3-year desensitization course, the AIT-TrAA group presented with lower SALT scores than the TrAA group, especially in non-alopecia totalis/universalis (AT/U) patients and pre-adolescent AT/U patients (age ≤ 14). In patients with elevated tIgE levels before AIT, a decrease in tIgE was correlated to reduced extent of AA on completion of the AIT course. After desensitization, elevation of IL-5 and decrease of IL-33 were observed in HDM allergic-AA patients. Desensitization to HDM in allergic AA patients reduces the severity of relapse-related hair loss over the 3-year AIT treatment course, possibly via opposing Th2 dominance. This adjunctive treatment may help reduce disease severity and curtail the disease process in allergic patients with AA.

Short- and long-term outcomes of laparoscopic or robotic radical gastrectomy based on preoperative perigastric artery CTA surgical decision-making: a high-volume center retrospective study with propensity score matching.

BACKGROUND: Some studies have demonstrated the short-term recovery course for patients who underwent laparoscopic gastrectomy according to preoperative computed tomography angiography (CTA) assessment. However, reports of the long-term oncological outcomes are still limited. METHODS: The data of 988 consecutive patients who underwent laparoscopic or robotic radical gastrectomy between January 2014 and September 2018 were analyzed retrospectively at our center, and propensity score matching was used to eliminate bias. Study cohorts were divided into the CTA group (n = 498) and the non-CTA group (n = 490) depending on whether preoperative CTA was available. The primary and secondary endpoints were the 3-year overall survival (OS) and disease-free survival (DFS) rates and the intraoperative course and short-term outcomes, respectively. RESULTS: 431 patients were included in each group after PSM. Compared with the non-CTA group, the CTA group had more harvested lymph nodes and less operative time, blood loss, intraoperative vascular injury and total cost, especially in the subgroup analysis with BMI ≥ 25 kg/m2 patients. There was no difference in the 3 year OS and DFS between the CTA group and the non-CTA group. When further stratified by BMI < 25 or ≥ 25 kg/m2, the 3-year OS and DFS were significantly higher in the CTA group than in the non-CTA group in terms of BMI ≥ 25 kg/m2. CONCLUSIONS: Laparoscopic or robotic radical gastrectomy based on preoperative perigastric artery CTA surgical decision-making has the possibility of improving short-term outcomes. However, there is no difference in the long-term prognosis, except for a subgroup of patients with BMI ≥ 25 kg/m2.

Comparison of short- and long-term outcomes between laparoscopic and open gastrectomy for locally advanced gastric cancer following neoadjuvant chemotherapy: a propensity score matching analysis.

BACKGROUND: This study was performed to evaluate the safety and efficacy of laparoscopic gastrectomy (LG) in patients with locally advanced gastric cancer (LAGC) who received neoadjuvant chemotherapy (NACT). METHODS: We retrospectively analyzed patients who underwent gastrectomy for LAGC (cT2-4aN+M0) after NACT from January 2015 to December 2019. The patients were divided into a LG group and an open gastrectomy (OG) group. The short- and long-term outcomes in both groups were examined following propensity score matching. RESULTS: We retrospectively reviewed 288 patients with LAGC who underwent gastrectomy following NACT. Of these 288 patients, 218 were enrolled; after 1:1 propensity score matching, each group comprised 81 patients. The LG group had significantly lower estimated blood loss than the OG group [80 (50-110) vs. 280 (210-320) mL, P < 0.001) but a longer operation time [205 (186.5-222.5) vs. 182 (170-190) min, P < 0.001], a lower postoperative complication rate (24.7% vs. 42.0%, P = 0.002), and a shorter postoperative hospitalization period [8 (7-10) vs. 10 (8-11.5) days, P = 0.001]. Subgroup analysis revealed that patients who underwent laparoscopic distal gastrectomy had a lower rate of postoperative complications than patients in the OG group (18.8% vs. 38.6%, P = 0.034); however, such a pattern was not seen in patients who underwent total gastrectomy (32.3% vs. 45.9%, P = 0.251). The 3-year matched cohort analysis showed no significant difference in overall survival or recurrence-free survival (log-rank P = 0.816 and P = 0.726, respectively) (71.3% and 65.0% in OG vs. 69.1% and 61.7% in LG, respectively). CONCLUSION: In the short term, LG following NACT is safer and more effective than OG. However, the long-term results are comparable.

Allergy promotes alopecia areata in a subset of patients.

In this commentary, we focus on allergy as a facilitating factor in the pathogenesis of alopecia areata (AA). From previous studies on AA, it is well known that subsets of patients can have one or more of; seasonal relapse, comorbid atopic rhinitis, asthma and dermatitis, lesion infiltrating eosinophils and plasma cells, high levels of total IgE, specific IgE for house dust mites (HDMs), and/or disrupted skin barrier function by the evaluation of filaggrin. Allergy and AA share a similar genetic background; both contributing to an immune reaction imbalance. Furthermore, adjunctive treatment with antihistamines, or desensitization for HDM, can reduce the severity of alopecia in atopic AA patients. Therefore, allergies may contribute to the onset and relapse of AA. Identification of an allergic or atopic immune component in AA patient subsets may indicate adjunctive treatment intervention measures against allergies should be taken which may improve the success of conventional AA treatment.

Sequential cyclic changes of hair roots revealed by dermoscopy demonstrate a progressive mechanism of diffuse alopecia areata over time.

BACKGROUND: Diffuse alopecia areata (DAA) often leads to a complete hair shedding within a few months. OBJECTIVE: To explore features and mechanisms underlying DAA. MATERIALS AND METHODS: Scalp and hair root dermoscopy were conducted on 23 DAA patients throughout the disease process, 20 patchy Alopecia areata patients, 23 acute telogen effluvium (ATE) patients and 10 normal controls. Histopathology was also evaluated. RESULTS: We found almost all hair roots were anagen in early stage DAA in 18 patients (18/23, 78.3%) within the first 4-8 weeks after hair loss onset. Anagen effluvium (~4 weeks) was followed by catagen (~4 weeks) and then telogen/exogen (~8 weeks) effluvium with overlap. Hair root and proximal hair shaft depigmentation was more prominent in later DAA disease stages. Black dots, exclamation mark hairs and inconsistent thickness of hair shafts were found more often in early than later DAA (Ps < 0.01). Early DAA histopathology revealed more prominent inflammation and hair follicle regression than that observed in the later stages. Patchy alopecia areata patients showed mixed anagen, catagen and telogen hair roots while ATE patients showed increased exogen and mildly decreased hair root pigmentation. CONCLUSION: Sequential cyclic staging of shed hairs in DAA indicates the insult may be hair-cycle specific. We suggest that DAA is initially an anagen effluvium disease involving an intense inflammatory insult, later progressing to a brief catagen effluvium, and then to telogen effluvium with premature exogen, in later stages of DAA.

Serum level of IL-4 predicts response to topical immunotherapy with diphenylcyclopropenone in alopecia areata.

BACKGROUND: This study investigated predictors of response to topical diphenylyclopropenone (DPCP) immunotherapy in patients with alopecia areata (AA). OBJECTIVE: To identify predictors of response, or resistance, to treatment for AA through clinical observations and serum tests. METHODS: Eighty four AA patients were treated with DPCP. Serum cytokine levels were measured in 33 AA patients pre- and post-treatment, and in 18 healthy controls, using ELISA assays. RESULTS: Of patients, 56.1% responded to DPCP with satisfactory hair regrowth; the response rate was negatively correlated with hair loss extent. Before DPCP treatment, higher serum IFN-γ and IL-12 cytokine levels were observed in AA patients compared to healthy controls. Non-responders to DPCP had significantly elevated serum IL-4 pre-treatment (3.07 fold higher) and lower IL-12 levels compared with responders. After DPCP treatment, non-responders had persistently high IL-4, increased IL-12, negligible decrease in IFN-γ and decreased IL-10. Post-treatment DPCP responders exhibited significantly decreased IFN-γ and IL-12, and increased IL-4 and IL-10. Development of adverse side-effects was significantly associated with higher pre-treatment serum IgE levels. LIMITATIONS: A small number of subjects were evaluated. CONCLUSIONS: Potentially, elevated pre-treatment serum levels of IL-4 and IL-12 can be used as unfavorable and favorable predictors of DPCP therapeutic effect, respectively. In addition, pre-treatment elevated serum total IgE may predict increased risk for severe adverse side-effects to DPCP application. Whether serum cytokine expression levels can be used as predictors of response to other forms of treatment is unknown, but it may warrant investigation in the development of personalized treatments for AA.

Evaluation of low impact development approach for mitigating flood inundation at a watershed scale in China.

Low impact development (LID) has attracted growing attention as an important approach for urban flood mitigation. Most studies evaluating LID performance for mitigating floods focus on the changes of peak flow and runoff volume. This paper assessed the performance of LID practices for mitigating flood inundation hazards as retrofitting technologies in an urbanized watershed in Nanjing, China. The findings indicate that LID practices are effective for flood inundation mitigation at the watershed scale, and especially for reducing inundated areas with a high flood hazard risk. Various scenarios of LID implementation levels can reduce total inundated areas by 2%-17% and areas with a high flood hazard level by 6%-80%. Permeable pavement shows better performance than rainwater harvesting against mitigating urban waterlogging. The most efficient scenario is combined rainwater harvesting on rooftops with a cistern capacity of 78.5 mm and permeable pavement installed on 75% of non-busy roads and other impervious surfaces. Inundation modeling is an effective approach to obtaining the information necessary to guide decision-making for designing LID practices at watershed scales.

Trends in culprit drugs and clinical entities in cutaneous adverse drug reactions: a retrospective study.

PURPOSE: Morbidity due to cutaneous adverse drug reactions (CADRs) is quite common. The specific culprit drugs change over time and clinicians must be kept informed with updated knowledge, thus preventing potential CADRs. This retrospective study is a survey of CADRs encountered in a hospital-based population in Southern China during three time intervals, from 1984 to 2015. MATERIALS AND METHODS: The clinical records were review of 306 patients with CADRs who were admitted to our hospital from 2011 to 2015. These data were compared with patients visiting our hospital during 1984-1994 and 2003-2010. RESULTS: From 2011 to 2015, the most common CADRs were exanthematous reactions (40.8%) and Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN; 17.0%). There were eight cases (2.6%) of CADRs related to targeted therapy in oncology. In the 205 CADR cases that were due to single medications, the most common offending drugs were allopurinol (21.5%), cephalosporins (10.7%) and carbamazepine (10.2%). The percentages of CADR cases due to allopurinol, carbamazepine, or epidermal growth factor receptor inhibitors were significantly higher from 2011 to 2015 compared with 1984-1994 or 2003-2010. The rate of SJS/TEN occurrence was significantly higher in the two recent periods compared with 1984-1994. CONCLUSIONS: Changes in drug prescriptions are a major factor that affects the CADRs seen in clinical records. Newer drugs can be culpable for CADRs, and more CADRs are now documented with increased severity at clinical presentation. Reliable screening tests for specific drugs are urgently required to eliminate possible fatalities.

Serum IFN-γ-inducible chemokines CXCL9 and CXCL10 are elevated in non-immediate drug hypersensitivity reactions.

BACKGROUND: The recruitment to the skin of drug-responsive T cells is responsible for the inflammatory profiles of non-immediate drug hypersensitivity reactions (niDHRs). Maculopapular exanthema (MPE) and Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) have quite distinct T cell infiltrating patterns. OBJECTIVE: To investigate serum levels of CXCL9, CXCL10 and IFN-γ in patients with niDHRs, including MPE and SJS/TEN, to evaluate correlations between the cytokines, and to determine whether the inflammatory factors correlate with clinical severity in patients with SJS/TEN. METHOD: Twenty-four patients with SJS/TEN, 24 patients with MPE, and 24 healthy donors with good tolerance to the drugs involved in the drug reactions were recruited into the study. The modified severity-of-illness score for TEN (SCORTEN) and detachment of body surface area (dBSA) were used to assess the clinical severity of SJS/TEN. Serum levels of CXCL9, CXCL10 and IFN-? were determined by ELISA. RESULTS: The niDHRs group, SJS/TEN and MPE subgroups all exhibited significantly higher levels of CXCL9, CXCL10 and IFN-γ compared with the control group (P < 0.001). Serum IFN-γ levels were positively correlated with CXCL9 levels and CXCL10 levels in patients with niDHRs (rs = 0.576, rs = 0.449, P < 0.05). None of the levels of CXCL9, CXCL10 and IFN-γ had any correlation with modified SCOTEN index or dBSA in SJS/TEN group. CONCLUSIONS: The results suggest Th1 cytokine IFN-γ and chemokines CXCL9 and CXCL10 may play roles in the pathogenesis of niDHRs.

Embryo transfer by reproductive endocrinology fellows vs attending physicians: are live birth rates comparable?

OBJECTIVE: To compare live birth rates following ultrasound-guided embryo transfer (ET) by reproductive endocrinology and infertility fellows versus attending physicians. STUDY DESIGN: Women who underwent their first day-3, fresh, nondonor ET between Oct. 1, 2005, and April 1, 2011, at our academic center were included in this retrospective cohort study. Embryos were designated high quality if they had 8 cells, less than 10% fragmentation, and no asymmetry. ET was performed with the afterload technique under ultrasound guidance. Categorical variables were evaluated with the χ(2) test and continuous variables with the Student t test. Logistic regression was performed to assess the relationship between ET physician and live birth rate while adjusting for potential confounders. RESULTS: Seven hundred sixty women underwent ET by an attending physician, and 104 by a fellow. Baseline characteristics were similar between the groups. The live birth rate was 31% following ET by an attending physician, compared with 34% following ET by a fellow (P = .65). Logistic regression adjusting for potential confounders demonstrated no significant association between ET physician and live birth rate. CONCLUSION: This retrospective study demonstrated no significant difference in live birth rates following ultrasound-guided ET by fellows vs attending physicians at our institution. These data suggest that academic practices using the afterload method and ultrasound guidance can train fellows to perform ET without compromising success rates.

Chemokine expression in diverse nonimmediate drug hypersensitivity reactions: focus on thymus activation-regulated chemokine, cutaneous T-cell-attracting chemokine, and interleukin-10.

BACKGROUND: Skin infiltration of different types of T lymphocytes is responsible for inflammatory profiles of nonimmediate drug hypersensitivity reactions (niDHRs). Important chemokines attracting skin-specific homing T cells include thymus activation-regulated chemokine (TARC) and cutaneous T-cell-attracting chemokine (CTACK). Interleukin-10 (IL-10) is a potent chemokine attracting CD8(+) T cells. OBJECTIVE: To investigate serum levels of TARC, CTACK, and IL-10 in patients with niDHRs and evaluate the correlation among these 3 chemokines. METHODS: Forty patients, including 19 patients with Stevens-Johnson syndrome and toxic epidermal necrolysis and 21 patients with maculopapular exanthema, and 21 healthy donors were recruited into the study. Clinical data of patients were obtained. Serum TARC, CTACK, and IL-10 levels were determined by enzyme-linked immunosorbent assay. RESULTS: Serum levels of TARC, CTACK, and IL-10 were significantly elevated in patients with niDHRs compared with those in normal controls (P < .05, P < .001, P < .001, respectively). The CTACK and IL-10 levels were significantly higher (P < .05, P < .001) in patients with Stevens-Johnson syndrome and toxic epidermal necrolysis than in normal controls. Patients with maculopapular exanthema exhibited higher levels of TARC, CTACK, and IL-10 compared with normal controls (P < .001, P < .001, P < .05). Serum CTACK levels were positively correlated with TARC levels in all 40 patients (rs = 0.3422, P < .05). Serum CTACK levels positively correlated with detachment of body surface area in patients with Stevens-Johnson syndrome and toxic epidermal necrolysis (rs = 0.510, P < .05). CONCLUSION: These results support a role for TARC, CTACK, and IL-10 in the pathogenesis of niDHRs for their chemotactic ability to attract different T-cell subtypes and different functional severities in niDHRs.

Early stage alopecia areata is associated with inflammation in the upper dermis and damage to the hair follicle infundibulum.

BACKGROUND/OBJECTIVES: Alopecia areata (AA) is a non-scarring inflammatory hair loss disease. We investigated the early pathological changes of AA to identify possible factors participating in its pathogenesis. METHODS: Clinical, laboratory and pathological features of 87 AA patients were investigated. RESULTS: Anti-nuclear antibody was found in 11 of 85 patients tested (13%), with a higher percentage in women (21%) than men (5%) (P = 0.026). In early AA lesions, inflammatory infiltration in the upper dermis and epithelial cell damage of the hair follicle infundibulum, just above the sebaceous gland, was observed. Liquefaction and disarrangement of peripheral infundibular epithelial cells coexisted with T-lymphocytic invasion and regression of the lower follicle. The latter findings positively correlated with the presence of eosinophils and perivascular mononuclear cell infiltration in the upper dermis. Eosinophilic infiltration was found in 35 patients (40%) and was positively correlated to elevated serum IgE levels (r = 0.21, P = 0.044), a more severe perivascular lymphocytic inflammation in the upper dermis (r = 0.24, P = 0.026), as well as a prominent swarm of bees-like peri-follicular infiltration (r = 0.41, P < 0.001). Mast cells were abundant in the upper dermis, especially around blood vessels, and positively correlated with eosinophil presence (r = 0.30, P = 0.027). CONCLUSION: Damage to the hair follicle infundibulum in the upper dermis might be an important component of early changes in AA lesions, possibly caused by lymphocyte cell infiltration in the same area. AA may involve damage of the upper hair follicle as well as the bulb, possibly involving hypersensitivity and autoimmunity.

Hair repigmentation and regrowth in a dupilumab-treated paediatric patient with alopecia areata and atopic dermatitis: a case report.

Alopecia areata (AA) is a chronic inflammatory disease mainly involving Th1 immunoreaction, but Th2 is also involved. A 9-year-old girl presented to our clinic with severe alopecia for 2 months and pruritus-related rashes for 8 years. She was diagnosed with AA and atopic dermatitis (AD), and the Severity of Alopecia Tool (SALT) score was 98. She used a 0.05% halometasone cream (occlusive dressing) topically applied overnight (6 days weekly) for 10 months. After 2 months of treatment, she had regrowth of both black and white hair. However, relapse occurred and she gradually lost all black terminal hair, but white terminal hair remained, with a SALT score of 70. Continuous topical occlusion resulted in white hair regrowth with a SALT score of 20 at the end of month 10. Dupilumab was initially prescribed as a 600-mg subcutaneous injection and maintained at 300 mg every 4 weeks thereafter. Hair repigmentation (10% of whole hair density) started, with black hair shaft appearing at the proximal end in parietal-occipital and occipital areas after three injections at week 12 of dupilumab therapy, with a SALT score of 10. After seven injections at week 28, the percentage of black hair shaft reached up to 90, and she regained her black hair and the pigmented section of hair shaft continued to grow longer at the rate of normal hair growth. Nevertheless, 4 months after termination of dupilumab therapy, the black terminal hair began to fall off, and white vellus hair gradually regrew on the scalp, with a SALT score of 80. Dupilumab induces hair regrowth and repigmentation of white terminal hair without disturbing the anagen phase of hair follicles. Therefore, melanocytes in AA may be a potential target of Th2-related factors. Persistent regrowth of white hair may be used as a signal of Th2 dominance in AA management.

Intraoperative performance and outcomes of robotic and laparoscopic total gastrectomy for gastric cancer: A high-volume center retrospective propensity score matching study.

BACKGROUND: Studies on robotic total gastrectomy (RTG) are currently limited. This study aimed to compare the intraoperative performance as well as short- and long-term outcomes of RTG and laparoscopic total gastrectomy (LTG). METHODS: A total of 969 patients underwent robotic (n = 161) or laparoscopic (n = 636) total gastrectomy between October 2014 and October 2021. The two groups of patients were matched 1:3 using the propensity score matching (PSM) method. The intraoperative performance as well as short- and long-term outcomes of the robotic (n = 147) and the laparoscopic (n = 371) groups were compared. RESULTS: After matching, the estimated intraoperative blood loss was lower (80.51 ± 68.77 vs. 89.89 ± 66.12, p = 0.008), and the total number of lymph node dissections was higher (34.74 ± 12.44 vs. 29.83 ± 12.22, p < 0.001) in the RTG group compared with the LTG group. More lymph node dissections at the upper edge of the pancreas were performed in the RTG group than in the LTG (12.59 ± 4.18 vs. 10.33 ± 4.58, p = 0.001). Additionally, postoperative recovery indicators and laboratory data were greater in the RTG group than those in the LTG group, while postoperative complications were comparable between the two groups (19.0% vs. 18.9%, p = 0.962). For overweight or obese patients with body mass indexes (BMIs) ≥25, certain clinical outcomes of the RTG remained advantageous, and no significant differences in three-year overall survival (OS) or relapse-free survival (RFS) were observed. CONCLUSIONS: Robotic total gastrectomy demonstrated better intraoperative performance, could improve the short-term clinical outcomes of patients, and was more conducive to patient recovery. However, the long-term efficacies of the two approaches were similar. Robotic surgical systems may reduce surgical stress responses in patients, allowing them to receive postoperative chemotherapy sooner.

A plain language summary on ritlecitinib treatment for adults and adolescents with alopecia areata.

WHAT IS THIS SUMMARY ABOUT?: This is a summary of the results of the ALLEGRO phase 2b/3 clinical trial, originally published in The Lancet. ALLEGRO-2b/3 looked at how well and safely the study medicine, ritlecitinib, works in treating people with alopecia areata ('AA' for short). The immune system protects your body from outside invaders such as bacteria and viruses. AA is an autoimmune disease, meaning a disease in which one's immune system attacks healthy cells of the body by mistake. In AA, the immune system attacks hair follicles, causing hair to fall out. AA causes hair loss ranging from small bald patches to complete hair loss on the scalp, face, and/or body. Ritlecitinib is a medicine taken as a pill every day, by mouth, that is approved for the treatment of severe AA. It blocks processes that are known to play a role in causing hair loss in patients with AA. WHAT WERE THE RESULTS OF THE STUDY?: Adults and adolescents (12 years and older) took part in the ALLEGRO-2b/3 study. They either took ritlecitinib for 48 weeks or took a placebo (a pill with no medicine) for 24 weeks. Participants taking placebo later switched to taking ritlecitinib for 24 weeks. The study showed that participants taking ritlecitinib had more hair regrowth on their scalp after 24 weeks than those taking the placebo. Hair regrowth was also seen on the eyebrows and eyelashes in participants taking ritlecitinib. Hair regrowth continued to improve to week 48 with continued ritlecitinib treatment. In addition, more participants taking ritlecitinib reported that their AA had 'moderately' or 'greatly' improved after 24 weeks than those taking the placebo. Similar numbers of participants taking ritlecitinib or placebo had side effects after 24 weeks. Most side effects were mild or moderate. WHAT DO THE RESULTS OF THE STUDY MEAN?: Ritlecitinib was an effective and well-tolerated treatment over 48 weeks for people with AA. Clinical Trial Registration: NCT03732807 (phase 2b/3 ALLEGRO study).

Prenatal alcohol exposure alters the course and severity of adjuvant-induced arthritis in female rats.

Prenatal alcohol exposure (PAE) has adverse effects on the development of numerous physiological systems, including the hypothalamic-pituitary-adrenal (HPA) axis and the immune system. HPA hyper-responsiveness and impairments in immune competence have been demonstrated. The present study investigated immune function in PAE females utilizing an adjuvant-induced arthritis (AA) model, widely used as a model of human rheumatoid arthritis. Given the effects of PAE on HPA and immune function, and the known interaction between HPA and immune systems in arthritis, we hypothesized that PAE females would have heightened autoimmune responses, resulting in increased severity of arthritis, compared to controls, and that altered HPA activity might play a role in the immune system changes observed. The data demonstrate, for the first time, an adverse effect of PAE on the course and severity of AA in adulthood, indicating an important long-term alteration in functional immune status. Although overall, across prenatal treatments, adjuvant-injected animals gained less weight, and exhibited decreased thymus and increased adrenal weights, and increased basal levels of corticosterone and adrenocorticotropin, PAE females had a more prolonged course of disease and greater severity of inflammation compared to controls. In addition, PAE females exhibited blunted lymphocyte proliferative responses to concanavalin A and a greater increase in basal ACTH levels compared to controls during the induction phase, before any clinical signs of disease were apparent. These data suggest that prenatal alcohol exposure has both direct and indirect effects on inflammatory processes, altering both immune and HPA function, and likely, the normal interactions between these systems.

Sperm chromatin integrity may predict future fertility for unexplained recurrent spontaneous abortion patients.

The pathogenesis of recurrent spontaneous abortion (RSA) is multi-factorial, complex and poorly understood. In the present study, semen parameters, including sperm chromatin integrity, sperm concentration, sperm motility and sperm morphology, were compared between 111 men whose partners had a history of unexplained RSA (RSA group) and 30 healthy fertile men (control group). The RSA group was further separated into three subgroups, depending on their reproductive outcome during the 12 months after they were enrolled in the study: the pregnancy subgroup consisted of 43 men whose partners achieved a successful pregnancy up to at least the 24th week of gestation; the abortion subgroup included 31 men whose partners experienced further abortions; and the infertile subgroup had 37 men whose partners did not have any positive pregnancy test after regular, unprotected intercourse. Significantly lower proportion of sperm with normal morphology was found in the abortion subgroup (14.7 ± 4.3%) than in the control group (17.5 ± 5.0%). Sperm concentrations were significantly lower in the infertile subgroup (55.7 ± 24.1%) than in the controls (68.6 ± 27.8%). The rates of abnormal sperm chromatin integrity were significantly higher in the abortion (16.7 ± 7.7%) and infertile (16.3 ± 6.6%) subgroups, compared to the control group (13.0 ± 4.4%). Logistic regression analysis showed that the subsequent reproductive outcome of the 111 RSA patients was negatively correlated to the rates of abnormal sperm chromatin integrity. In conclusion, sperm chromatin integrity, sperm morphology, and sperm concentration were associated with future reproductive outcome of RSA patients. The sperm chromatin integrity was a significant predictor for future abortion and infertility.

Effect of perioperative probiotic supplements on postoperative short-term outcomes in gastric cancer patients receiving neoadjuvant chemotherapy: A double-blind, randomized controlled trial.

OBJECTIVES: Surgery can significantly improve the prognosis of patients with gastric cancer. However, some patients are at a later stage at diagnosis and need to receive neoadjuvant chemotherapy (NACT). Previous studies have shown that NACT may lead to more postoperative complications. Probiotics have the potential to reduce postoperative complications and infections, but no similar clinical trials have been conducted in patients with gastric cancer receiving NACT. The aim of this study was to investigate the effect of probiotics on postoperative infections and other short-term outcomes in patients with gastric cancer receiving NACT. METHODS: This was a randomized, double-blind, controlled trial. All patients who underwent minimally invasive surgery after NACT were included and randomized into a probiotic group (PG; n = 33) or a control group (CG; n = 33). Postoperative infectious complications, recovery of gastrointestinal function, postoperative hospital stay, medical costs, time to initiate adjuvant chemotherapy, 30-d readmission and mortality, and common laboratory inflammatory indexes were observed. RESULTS: PG patients had significantly fewer postoperative infections (P = 0.027). Time to first flatus and bowel movement was quicker (P = 0.001 and P < 0.001, respectively) and inflammatory indexes were lower in the PG patients. Postoperative hospital length of stay was shorter in the PG than in the CG (P = 0.001). Due to fewer postoperative infections and faster recovery, adjuvant chemotherapy was initiated earlier in PG patients (P < 0.001). CONCLUSIONS: Perioperative probiotic supplements can reduce postoperative infection, improve short-term clinical outcomes, and reduce the level of common inflammatory indicators in patients with gastric cancer receiving NACT. Patients in the PG started adjuvant chemotherapy earlier than CG patients.