Clinical and Immunological Features, Genetic Variants, and Outcomes of Patients with CD40 Deficiency.

PURPOSE: Inherited deficiencies of CD40 and CD40 ligand (CD40L) reflect the crucial immunological functions of CD40-CD40L interaction/signaling. Although numerous studies have provided a detailed description of CD40L deficiency, reports of CD40 deficiency are scarce. Herein, we describe the characteristics of all reported patients with CD40 deficiency. METHODS: The PubMed, Embase and Web of Science databases were searched for relevant literature published till 7th August 2023. Study deduplication and identification of relevant reports was performed using the online PICO Portal. The data were extracted using a pre-designed data extraction form and the SPSS software was used for analysis. RESULTS: Systematic literature review revealed 40 unique patients with CD40 deficiency. Respiratory tract and gastrointestinal infections were the predominant clinical manifestations (observed in 93% and 57% patients, respectively). Sclerosing cholangitis has been reported in nearly one-third of patients. Cryptosporidium sp. (29%) and Pneumocystis jirovecii (21%) were the most common microbes identified. Very low to undetectable IgG levels and severely reduced/absent switch memory B cells were observed in all patients tested/reported. Elevated IgM levels were observed in 69% patients. Overall, splice-site and missense variants were the most common (36% and 32%, respectively) molecular defects identified. All patients were managed with immunoglobulin replacement therapy and antimicrobial prophylaxis was utilized in a subset. Hematopoietic stem cell transplantation (HSCT) has been performed in 45% patients (curative outcome observed in 73% of these patients). Overall, a fatal outcome was reported in 21% patients. CONCLUSIONS: We provide a comprehensive description of all important aspects of CD40 deficiency. HSCT is a promising curative treatment option for CD40 deficiency.

Basic Investigations in Pediatric Rheumatology.

The spectrum of pediatric rheumatological disorders is diverse and they are important differential diagnoses in a variety of clinical scenarios. Basic investigations not only provide supporting evidence for the diagnosis of a rheumatological illness but also help in exclusion of other diseases as well as for monitoring the activity of disease. Among these, complete blood count, biochemical assays including tests for inflammatory response, urine analysis, and various autoantibodies are often used. In addition, depending on the clinical features, imaging and tissue biopsies are used to confirm the diagnosis.

Long-Term Outcomes of Autologous Hematopoietic Stem Cell Transplant (HSCT) for Multiple Myeloma: While New Horizons Emerge, It Is Still Only a Silver Lining for Resource-Constrained Settings.

Background Significant hurdles impede the optimal implementation of hematopoietic stem cell transplantation (HSCT) in low-middle income countries (LMICs). Herein, we highlight the challenges faced in LMICs while performing HSCT and report the long-term outcomes of patients with newly diagnosed multiple myeloma (MM) who underwent autologous HSCT (AHSCT) at our center. Besides, we provide a comprehensive review of studies reporting long-term outcomes of AHSCT in MM from the Indian subcontinent. Methodology This study was conducted at the State Cancer Institute, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, India. Case records of all patients with MM who received AHSCT from December 2010 to July 2018 were reviewed retrospectively. A non-systematic literature search was performed using PubMed and Google Scholar databases. Data regarding clinicopathological parameters and long-term follow-up were extracted from relevant studies and for patients included in our study. Results At our center, 47 patients (median age 52.0 years) with MM underwent AHSCT. Majority of patients had stage III disease (ISS) and median time to transplant was 11.5 months. The five-year progression free survival (PFS) and overall survival (OS) were 59.1% and 81.2%, respectively. Studies from the Indian subcontinent have observed a five-year OS of ~50% to ~85%. However, a greater variability in the five-year PFS has been reported, ranging from ~20% to ~75%. The median time to transplant has ranged from seven to 17 months (indicating time delays) with median CD34 cell counts of 2.7-6.3×106 cells/kg (lower than developed countries). Conclusions Despite significant resource limitations in LMICs, AHSCT is increasingly been performed in MM with encouraging long-term outcomes.

Vascular dysfunction in juvenile idiopathic arthritis: a systematic review and meta-analysis.

We performed a systematic review and meta-analysis of studies evaluating vascular function in patients with JIA. Relevant literature published from 1st January 1965 to 1st March 2022 was searched systematically utilizing PubMed, Web of Science, and Embase databases. Observational studies were included-patients with JIA (classified according to the International League of Associations for Rheumatology criteria) were included as cases (study population) and age/sex-matched healthy participants as controls (comparator group). Outcome measures were differences in non-invasive parameters of vascular function. Online Population, Intervention, Comparison, Outcomes Portal was used for deduplication of studies and data extraction. Review Manager, Comprehensive Meta-analysis, and Meta-Essential softwares were used for data synthesis/analysis (encompassing data pooling and evaluation of heterogeneity and publication bias). Newcastle-Ottawa Scale and GRADEpro GDT software were utilized to assess study quality and certainty of evidence, respectively. Of 338 citations, 17 observational studies with 1423 participants (cases = 757, controls = 666) were included. Carotid intima-media thickness (CIMT) was higher [mean difference (MD) 0.02 mm {95% confidence interval (CI) 0.01-0.04}, p = 0.0006, I2 = 69%] in patients with JIA. Besides, decreased flow-mediated dilatation (FMD) [MD - 2.18% {95%CI - 3.69- - 0.68}, p = 0.004, I2 = 73%] was also observed. Results of studies assessing pulse wave velocity or arterial stiffness could not be pooled due to significant methodological variations. A 'very low' certainty of evidence suggests the presence of vascular dysfunction in JIA. Future longitudinal studies are required to determine whether altered CIMT and FMD in patients with JIA translate to an enhanced risk of (adverse) clinical cardiovascular events. PROSPERO (CRD42022323752).