Changing Phenotypes and Clinical Outcomes Over Time in Microscopic Polyangiitis

Introduction: Diagnosis and management of microscopic polyangiitis (MPA) have evolved considerably over the past decades, but it is unknown whether clinical and histological presentation and patient and renal outcomes have changed accordingly. Methods: We compared clinical and histopathological characteristic at diagnosis, risk of death, end-stage kidney disease (ESKD), and relapse rate in patients diagnosed with MPA between 1980 and 2022, after grouping them in 2 periods (p): p1980–2001 and p2002–2022. We compared the mortality rate between the 2 periods using Kaplan-Meier estimator and Cox-regression, and competing risks of ESKD and death using the Aalen–Johansen estimator, Fine-Gray multiple regression, and multistate models. Results: Out of 187 patients, 77 were in p1980–2001 and 110 in p2002 to 2022. Patients in p2002 to 2022 were older (66.2 ± 14.0 SD vs. 57.7 ± 15.8; P < 0.001), had a better kidney function (estimated glomerular filtration rate [eGFR] 25.9 ± 24.8 vs. 21.5 ± 28.2 ml/min per 1.73 m2; P = 0.011) and a lower prevalence of the Berden sclerotic class (5.9 vs. 20.9%; P = 0.011). Despite a similar crude and adjusted patient survival, the risk of ESKD decreased during p2002 to 2022 (subdistribution hazard ratio [HR] 0.30, 95% confidence interval [CI]: 0.16–0.57; P < 0.001). The results remained significant after accounting for death after ESKD and after adjusting for potential confounders (HR 0.33 [95% CI: 0.18–0.63; P < 0.001]). The risk of relapse was numerically higher during p2002 to 2022 (subdistribution-HR 1.64 [95% CI: 0.95–2.83; P = 0.075]). Conclusion: MPA kidney involvement has become less severe over the past decades, leading to a reduced risk of ESKD and a higher relapse rate, despite a comparable risk of death

Transplacental injection of somite-derived cells in mdx mouse embryos for the correction of dystrophin deficiency

Duchenne muscular dystrophy (DMD) is a lethal recessive disease caused by the absence of dystrophin in skeletal muscle, heart and other tissues. No cure is available at present for DMD. Here we describe a new strategy for the correction of dystrophin deficiency based on the transplantation of normal somite-derived cells into mdx mouse embryos. Somite-derived cells were isolated from E11.5 transgenic mouse embryos expressing the LacZ gene under the control of the muscle-specific desmin promoter and injected into the uterine circulation of pregnant mdx mice at gestational days E11.5-E17. Approximately 30% of the injected mdx embryos survived the procedure. Donor somite-derived cells were able to cross the placenta and migrate into host embryonic tissues. The pattern of donor cell distribution in host tissues depended on the gestational age of the transplanted embryos. Cells were found in hindlimb muscles, diaphragm, heart and ribs in E11.5 treated embryos and in the skull, ribs, vertebrae and lung of E15-E17 treated embryos. Normal dystrophin transcripts were detected in muscle and bone by RT-PCR. Histochemical analysis showed co-localization of LacZ and dystrophin expression in 5% of soleus and quadriceps muscle fibres and in 4% of heart myocytes of two of seven 8-week-old treated mdx mice

Paget disease of the vulva an analysis of 24 cases

Paget's disease can arise in the breast (mammary Paget disease) or in other locations (extramammary Paget disease) such as anogenital skin in both males and females (Paget disease of the vulva [PDV]). Underlying adenocarcinoma can be found in some cases. This study aims to report clinical aspects, surgical procedures, outcomes, and recurrences of patients with PDV.A retrospective chart review was conducted on patients with pathologically confirmed diagnosis of PDV managed at the Department of Obstetrics and Gynecology, University of Bari, and the "Giovanni Paolo II" National Cancer Institute in Bari, between 1998 and 2018.Records of 24 cases of PDV were examined. Median age of the patients at diagnosis was 69.3 (range 38-84), diagnosis of synchronous cancer was made in 2 cases and in 2 other cases of metachronous disease. Three patients had previously been diagnosed with other oncological diseases. All patients underwent surgery including wide local excision (6), simple vulvectomy (8), and extended vulvectomy (10). Lymphadenectomy was performed in 2 cases and reconstructions with advancement flaps in 7 cases. Four patients were found to have invasive disease and 1 had inguinal node involvement. Positive margins were found in 11 patients. Wound dehiscence and urethral stenosis were found in 4 and 1 case each. Eight recurrences (33.33%) were observed, regardless of positive surgical margins.PDV has a low rate of malignancy but a high rate of recurrence. It should be diagnosed early to avoid repeated surgery and to reduce symptoms and morbidity

Risk Factors for Retinal Detachment: A Case-Control Study

Objective:The aim of this study was to investigate risk factors for retinal detachment or tear (RD/T), and follow up two studies that found increased risk from work-related heavy lifting.Methods:We conducted a case-control study including 200 cases of RD/T and 415 controls. Participants completed a questionnaire covering general health, vision, and physical exertion. Multiple logistic regression and propensity score matching was used to control confounding and estimate independent effects.Results:RD/T risk was increased by one lifting measure: current regular lifting of more than 30lbs (>13.6kg). In the population aged less than 65 years, the odds ratio comparing those with/without heavy lifting was 1.81, 95% confidence interval=1.08 to 3.04.Conclusion:Occupational heavy lifting may represent a risk factor for RD/T, but further research is needed in populations with frequent heavy physical exertion to more precisely quantify the risk