Profile of 208 patients with inborn errors of immunity at a tertiary care center in South India.

Primary immune deficiencies or inborn errors of immunity (IEI) are a heterogeneous group of disorders that predispose affected individuals to infections, allergy, autoimmunity, autoinflammation and malignancies. IEIs are increasingly being recognized in the Indian subcontinent. Two hundred and eight patients diagnosed with an IEI during February 2017 to November 2021 at a tertiary care center in South India were included in the study. The clinical features, laboratory findings including microbiologic and genetic data, and treatment and outcome details were analyzed. The diagnosis of IEI was confirmed in a total of 208 patients (198 kindreds) based on relevant immunological tests and/or genetic tests. The male-to-female ratio was 1.8:1. Of the 208 patients, 72 (34.6%) were < 1 yr, 112 (53.8%) were 1-18 years, and 24 (11.5%) were above 18 years. The most common IEI in our cohort was SCID (17.7%) followed by CGD (12.9%) and CVID (9.1%). We also had a significant proportion of patients with DOCK8 deficiency (7.2%), LAD (6.2%) and six patients (2.8%) with autoinflammatory diseases. Autoimmunity was noted in forty-six (22%) patients. Molecular testing was performed in 152 patients by exome sequencing on the NGS platform, and a genetic variant was reported in 132 cases. Twenty-nine children underwent 34 HSCT, and 135 patients remain on supportive therapy such as immunoglobulin replacement and/or antimicrobial prophylaxis. Fifty-nine (28.3%) patients died during the study period, and infections were the predominant cause of mortality. Seven families underwent prenatal testing in the subsequent pregnancy. We describe the profile of 208 patients with IEI, and to the best of our knowledge, this represents the largest data on IEI from the Indian subcontinent reported so far.

What you see may not be what you get! Simulate towards effective planning of pediatric intensive care unit.

Aims and objectives: This study aimed to describe the application of low-cost inter-professional simulation over 4 phases in identifying structural and design issues, latent safety threats as well as test systems, processes, including facilitated team training during the design of a new pediatric intensive care unit (PICU). Materials and methods: The four-phase inter-professional simulation sessions involving clinical and non-clinical teams were conducted over a 3-month period in a corporate hospital during the designing of a new PICU. Low-cost resources, such as floor tapes, low-tech manikins, reused sterilized consumables, and actual patient beds and equipment, were used for the in situ simulation sessions. A plus-delta method of debriefing was done, and changes agreed on consensus were implemented after each simulated session. Results: There were 10 simulation sessions conducted over 4 phases during the 3-month period of designing the PICU. The participants included 10 doctors from PICU and adult critical care, 25 critical care nurses, 12 members from the project team, and 2 hospital administrators in various combinations. The first phase led to the re-design of workspace and clinical areas for better space utilization. The second phase required further revision to facilitate better mobility and facilities. In the third phase, the number of beds was reduced to 6 beds following the simulated drills involving the actual placement of patient cots and equipment. The fourth phase had thematic 5 simulated exercises involving the newly recruited clinical teams that enabled the identification of systems and process issues. Cognitive aids and video orientation of the setup, team training, and human factors training were addressed, and the unit was open for patient care in a week. Conclusion: A phased inter-professional simulation exercise with low-cost resources can enable the identification of structural challenges, design issues, latent safety threats, test systems, processes, patient flow, and facilitated team training during the design of a new PICU. Further studies are needed to understand the generalization of the study findings into designing PICU.

Clinical, Immunological, and Molecular Profile of Chronic Granulomatous Disease: A Multi-Centric Study of 236 Patients From India.

Background: Chronic granulomatous disease (CGD) is an inherited defect in phagocytic respiratory burst that results in severe and life-threatening infections in affected children. Single center studies from India have shown that proportion of autosomal recessive (AR) CGD is more than that reported from the West. Further, affected patients have high mortality rates due to late referrals and difficulties in accessing appropriate treatment. However, there is lack of multicentric collaborative data on CGD from India. Objective: To describe infection patterns, immunological, and molecular features of CGD from multiple centers in India. Methods: A detailed proforma that included clinical and laboratory details was prepared and sent to multiple centers in India that are involved in the care and management of patients with inborn errors of immunity. Twelve centers have provided data which were later pooled together and analyzed. Results: Of the 236 patients analyzed in our study, X-linked and AR-CGD was seen in 77 and 97, respectively. Male female ratio was 172:64. Median age at onset of symptoms and diagnosis was 8 and 24 months, respectively. Common infections documented include pneumonia (71.6%), lymphadenitis (31.6%), skin and subcutaneous abscess (23.7%), blood-stream infection (13.6%), osteomyelitis (8.6%), liver abscess (7.2%), lung abscess (2.9%), meningoencephalitis (2.5%), splenic abscess (1.7%), and brain abscess (0.9%). Forty-four patients (18.6%) had evidence of mycobacterial infection. Results of molecular assay were available for 141 patients (59.7%)-CYBB (44.7%) gene defect was most common, followed by NCF1 (31.9%), NCF2 (14.9%), and CYBA (8.5%). While CYBA variants were documented only in Southern and Western parts of India, a common dinucleotide deletion in NCF2 (c.835_836delAC) was noted only in North Indian population. Of the 174 patients with available outcome data, 67 (38.5%) had expired. Hematopoietic stem cell transplantation was carried out in 23 patients, and 12 are doing well on follow-up. Conclusions: In India, proportion of patients with AR-CGD is higher as compared to Western cohorts, though regional differences in types of AR-CGD exist. Clinical profile and mortality rates are similar in both X-linked and AR-CGD. However, this may be a reflection of the fact that milder forms of AR-CGD are probably being missed.