Healthcare resource utilization of patients with warm autoimmune hemolytic anemia initiating first line therapy of oral corticosteroids with or without rituximab.

This retrospective cohort study described real-world treatment patterns and healthcare resource utilization (HCRU) of patients with warm autoimmune hemolytic anemia (wAIHA) initiating treatment with first-line (1L) oral corticosteroids (OCS) + rituximab (R) compared to 1L OCS. Patients with a wAIHA diagnosis code (D59.11) between 8/2020-3/2022 were identified using US pharmacy and medical claims databases. Patients initiating 1L OCS ± R were identified (date of initiation = 'index date') with a 1-year pre-index period and a variable (minimum 1-year) follow-up period. The final sample comprised 77 1L OCS + R patients and 400 1L OCS patients (~ 60% female, mean age > 64 years). Over the 1-year follow-up, HCRU was higher in the OCS + R cohort with higher mean number of physician office visits (22.9 and 14.4; p < 0.01), including hematology/oncology office visits, and higher utilization of rescue therapy (59.7% and 33.3%; p < 0.01), driven by higher use of injectable corticosteroids. Patients in OCS + R and OCS groups completed 1L therapy after a similar mean duration of 103.5 and 134.6 days, respectively (p = 0.24). In the majority of patients, second-line (2L) therapy was initiated at a similar timepoint: 66.2% OCS + R and 72.0% OCS cohorts (p = 0.31) initiated 2L in a mean of 218.3 and 203.2 days (p = 0.76) after the end of 1L treatment, respectively. The addition of rituximab in 1L did not extend the remission period, with most patients in both cohorts initiating 2L therapy within less than 1 year of completing 1L treatment. 1L OCS + R patients also had substantial HCRU burden. More effective novel therapies are needed to address the high unmet need in wAIHA.

Results of a phase 2 trial of an oral CXCR4 antagonist, mavorixafor, for treatment of WHIM syndrome.

Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome is a rare primary immunodeficiency caused by gain-of-function mutations in the CXCR4 gene. We report the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of mavorixafor from a phase 2 open-label dose-escalation and extension study in 8 adult patients with genetically confirmed WHIM syndrome. Mavorixafor is an oral small molecule selective antagonist of the CXCR4 receptor that increases mobilization and trafficking of white blood cells from the bone marrow. Patients received escalating doses of mavorixafor, up to 400 mg once daily. Five patients continued on the extension study for up to 28.6 months. Mavorixafor was well tolerated with no treatment-related serious adverse events. At a median follow-up of 16.5 months, we observed dose-dependent increases in absolute neutrophil count (ANC) and absolute lymphocyte count (ALC). At doses ≥300 mg/d, ANC was maintained at >500 cells per microliter for a median of 12.6 hours, and ALC was maintained at >1000 cells per microliter for up to 16.9 hours. Continued follow-up on the extension study resulted in a yearly infection rate that decreased from 4.63 events (95% confidence interval, 3.3-6.3) in the 12 months prior to the trial to 2.27 events (95% confidence interval, 1.4-3.5) for patients on effective doses. We observed an average 75% reduction in the number of cutaneous warts. This study demonstrates that mavorixafor, 400 mg once daily, mobilizes neutrophil and lymphocytes in adult patients with WHIM syndrome and provides preliminary evidence of clinical benefit for patients on long-term therapy. The trial was registered at www.clinicaltrials.gov as #NCT03005327.

Potential anti-inflammatory effect of dapagliflozin in HCHF diet- induced fatty liver degeneration through inhibition of TNF-α, IL-1ß, and IL-18 in rat liver.

Non-alcoholic fatty liver (NAFLD) is accompanied by an increased expression of oxidative stress parameters, in addition to the inflammatory cytokines; tumor necrosis factor alpha (TNF-α), interleukin type 1beta (IL-1ß), and interleukin type 18 (IL-18). The aim of this study is to investigate the effect of dapagliflizon (DAPA) on high carbohydrate-high fat (HCHF) diet-induced expression of inflammatory cytokines in rat liver. NAFLD was induced by feeding the rats HCHF diet (consist of animal fat tallow and standard show pellets) and the consumption of fructose in drinking water (10%) for 12 or 18 weeks. The oral administration of DAPA (1 mg/kg/day) from 13th week to 18th week significantly improved NAFLD as indicated by a significant reduction in liver aminotransferases in addition to a significant decrease of serum MDA, cholesterol, triglyceride and LDL-cholesterol with concomitant significant elevation of HDL-cholesterol. DAPA-treated animals showed a significant reduction of liver homogenate content of TNF-α, IL-1ß, and IL-18. These results indicate that the administration of DAPA may be beneficial against HCHF diet-induced NAFLD. Histopathological examination of liver specimens supported the conclusion that DAPA improves steatohepatitis induced by HCHF diet.

[Plastic Surgical Correction of Buried Penis]. / Plastisch-chirurgische Korrektur des "Buried Penis".

A "buried penis" causes functional problems and embarrassment. In the past, this complex condition was only seen in extremely overweight patients or as a result of severe inflammations in this region. More recently, this problem has also been observed in patients with massive weight loss following bariatric surgery. In these patients there is an abundance of extremely flaccid skin in the suprapubic region, which covers the penis and causes it to "disappear". This leads to balanitis and, in turn, further retraction of the penis. The only solution to this condition is a sophisticated surgical approach in 3 phases: At first, suprapubic tissues must be lifted. Secondly, the penis must be completely denuded and debrided and the correct penopubic/penoscrotal angles must be reconstructed. The last phase includes a strainless coverage of the remaining defect of the penis. This condition has not been widely described in the literature. The general incidence and prevalence in the postbariatric population is unknown, probably due to patients' embarrassment and lack of knowledge on the physicians' end. Nevertheless, the buried penis can be successfully exposed through careful, structured surgical treatment and an interdisciplinary approach between plastic surgeons and urologists.