IntroductionTo assess the incidence and risk factors for breakthrough COVID-19 infection in a vaccinated cohort of patients with autoimmune rheumatic diseases (AIRDs) and determine whether antibodies to receptor binding domain of spike protein (anti-RBD) serve as a reliable predictor of susceptibility to such infections.MethodsPatients with AIRDs who had completed two doses of SARS-CoV2 vaccines were included and anti-RBD antibodies were determined 4–6 weeks post the second vaccine dose and stratified into good responders (GR) (>212 IU), inadequate responders (IR) (0.8–212 IU) and non-responders (NR) (<0.8 IU). Patients who had completed a minimum of 8 weeks interval after the second dose of vaccine were followed up every 2 months to identify breakthrough infections. All sero converted patients who had contact with COVID-19 were also analysed for neutralising antibodies.ResultsWe studied 630 patients of AIRDs (mean age 55.2 (±11.6) years, male to female ratio of 1:5.2). The majority of patients had received AZD1222 (495, 78.6%) while the remaining received the BBV152 vaccine. The mean antibody titre was 854.1 (±951.9), and 380 (60.3%) were GR, 143 (22.7%) IR and 107 (16.9%) NR.Breakthrough infections occurred in 47 patients (7.4%) at a mean follow-up of 147.3 (±53.7) days and were proportionately highest in the NR group (19; 17.75%), followed by the IR group (13; 9.09%) and least in the GR group (15; 3.95%). On log-rank analysis, antibody response (p<0.00001), vaccine(p=0.003) and mycophenolate mofetil (p=0.007) were significant predictors of breakthrough infections. On multivariate Cox regression, only NR were significantly associated with breakthrough infections (HR: 3.6, 95% CI 1.58 to 8.0, p=0.002). In sero converted patients with contact with COVID-19, neutralisation levels were different between those who developed and did not develop an infection.ConclusionBreakthrough infections occurred in 7.4% of patients and were associated with seronegativity following vaccination. This provides a basis for exploring postvaccination antibody titres as a biomarker in patients with AIRD.

Context.— Female adnexal tumor of probable Wolffian origin (FATWO) is an extremely rare gynecologic neoplasm of low malignant potential. Fewer than 90 cases of this entity have been described in the English-language literature. It is presumed to be derived from mesonephric (Wolffian) duct remnants in the upper female genital tract. We provide a literature review to increase awareness of this extremely uncommon entity. Objectives.— To review the clinical and pathologic findings of FATWO and to discuss common entities in the differential diagnosis. Data Sources.— The study involved PubMed (National Center for Biotechnology Information, Bethesda, Maryland) searches, including multiple review articles, case reports, retrospective studies, selected book chapters, and University of Mississippi Medical Center cases. Conclusions.— FATWO can affect patients from a wide age range and present with a nonspecific clinical presentation. It typically presents as solid tumors with occasional nodular, lobulated, or cystic appearances. FATWO can show a variety of histologic patterns which may result in diagnostic difficulties for pathologists. There is no single specific immunohistochemical stain for FATWO, and the pathogenesis and molecular alterations are not yet well understood. Although it is generally considered a benign entity, recurrent and metastatic cases have been reported. There are no current recommendations regarding the optimal clinical management of FATWO.

The purpose of this report was to compile relevant technical information on various alternative strategies that can be used as feasible approaches in the development of solid dispersions. The technologies discussed in the report are spray coating on sugar beads with a fluidized bed coating system, hot melt extrusion, direct capsule filling, electrostatic spinning, surface active carriers, and supercritical fluid technology. The focus is on basic principles, the equipment involved, and the relevant scale-up work. These technologies have been found to eliminate several drawbacks posed by the conventional methods of manufacturing of solid dispersions such as laborious preparation methods, reproducibility, scaling up of manufacturing processes, stability of drug, and vehicle.

BackgroundAutoimmune hemolytic anemia (AIHA) is a less recognized, potentially fatal condition. There is a scarcity of data on clinicoserological characteristics and response to therapy concerning this disease from South India.MethodsData for 33 patients with primary AIHA recorded from July 2009 to June 2015 were retrospectively analyzed for clinical presentation, response to frontline therapy, durability of response, time to next treatment (TTNT), and response to second-line agents.ResultsThe median follow-up period was 50 months. Among 33 patients, 48% of the cases were warm autoimmune hemolytic anemia (WAIHA), 46% were cold agglutinin disease (CAD), and 6% were atypical. Three-fourth of patients had severe anemia (<8 g/dL hemoglobin [Hb]) at onset; younger patients (age <40 yr) had more severe anemia. All of the patients who required treatment received oral prednisolone at 1.5 mg/kg/d as a frontline therapy, and the response rate was 90% (62% complete response [CR] and 28% partial response [PR]). The overall response to corticosteroids in WAIHA and CAD was 87% and 92%, respectively. The median corticosteroid duration was 14 months, and 50% of the patients required second-line agents. Fourteen patients received azathioprine as a second-line agent, and 11 of these patients responded well, with half of them not requiring a third agent. Four patients developed severe infections (pneumonia, sepsis, and soft tissue abscess) and two had life-threatening venous thrombosis. One case of death was recorded.ConclusionAIHA is a heterogeneous disease that requires care by physicians experienced in treating these patients.

No abstract

The treatment of genetic diseases using therapeutic gene transfer is considered to be a significant development. This development has brought with it certain limitations, and the process of overcoming these barriers has seen a drastic change in gene delivery. Many metal ions such as Mg2+, Mn2+, Ba2+ and, most importantly, Ca2+ have been demonstrated to have significant roles in gene delivery. Recently, calcium phosphate alone, or in combination with viral and nonviral vectors, was found to exert a positive effect on gene transfer when incorporated in the colloidal particulate system, which is an advancing approach to gene delivery. This review elaborates on various successful methods of using calcium in gene delivery.

Cancer chemotherapeutic agents are often administered systemically. Following systemic administration, numerous biological factors associated with the tumours influence the delivery of the drugs to the tumours. These factors have been extensively studied for the last 2 decades. The influence of these biological factors has brought about a drastic change in the design of drug delivery systems to solid tumours. This review discusses the various biological factors influencing drug delivery to tumours and the subsequent development of injectable delivery systems (i.e., lipid-based nanoparticles (SLNs)) for adequate delivery of drug to solid tumours.

Reduced IGF-I is associated with low bone mass in humans and mice. C3H/He/J (C3H) mice have higher skeletal IGF-I and greater bone mass than C57BL/6J (B6). We hypothesized that strain-related genotypic differences in Igf1 affected skeletal function. The Igf1 coding region is nonpolymorphic, but its 3' untranslated region (UTR) is polymorphic between C3H and B6. Luciferase-Igf1 3' UTR reporter constructs showed that these polymorphic regions did not affect UTR function. IGF-I splice variants give rise to a common mature IGF-I peptide, but different E peptides. We identified two splice products, exon 4+6 (Ea) and exon 4+5+6 (Eb, mechano-growth factor) and found that their abundance was unchanged during osteoblastic differentiation. The Igf1 3' UTR encoded by exon 6 contains alternative polyadenylation sites. Proximal site use produces a short 3' UTR of approximately 195 bases, whereas distal site usage results in an approximately 6300-base UTR. Although Igf1 mRNA levels did not change during osteoblastic differentiation, distal polyadenylation site usage was increased in B6 cells but not in C3H. The resulting long Igf1 RNA isoform is less stable and has decreased translation efficiency, which may be one mechanism contributing to decreased IGF-I in B6 vs. C3H mice. Although the long UTR contains a conserved [GU](18) repeat, which is a positive regulator of UTR activity, it is also targeted by negative regulators, miR-29 and miR-365. These microRNAs are increased in B6 and C3H cells during osteoblastic differentiation. Differential expression of the long Igf1 3' UTR isoform may be a possible mechanism for enhanced IGF-I regulation in B6 vs. C3H mice.