Clinical and Genetic Spectrum of Inborn Errors of Immunity in a Tertiary Care Center in Southern India

Objectives To study the incidence, clinical manifestations, and genetic spectrum of primary immunodefciency diseases (PID)/inborn errors of immunity (IEI) in a tertiary care hospital in Southern India. Methods A retrospective analysis of all patients with a clinical suspicion of PID/IEI seen at a tertiary care hospital was performed. All patients had at least one or more warning signs of PID. Serum immunoglobulin levels and other targeted investigations were performed as warranted by the clinical presentation. All families with suspected PID were counseled and ofered genetic testing. Results A total of 225 children were evaluated for PID during the study period of 6 y. Fifty-six of them did not meet the European Society of Immunodefciencies (ESID) criteria (working defnition of clinical diagnosis) and were excluded. An IEI was found in 30/49 (61.2%) patients. The most frequent reason for referral was recurrent/unusual or serious infections (28%), or cytopenia (16%). Group IV diseases of immune dysregulation was the most common category (19%), followed by group III predominant antibody defciencies in 23/163 (14%), as per the International Union of Immunological Societies (IUIS) classifcation. Conclusions This study highlights the heterogeneity of the present cohort, the underuse of genetic tests, and eforts to provide optimal care for children with possible IEI in this center.

De novo double-hit B-cell precursor leukemia/lymphoma - an unusual presentation as peritoneal lymphomatosis

Peritoneal lymphomatosis (PL) is a rare presentation of extranodal precursor leukemia/lymphoma. The presentation is often non-specific, leading to delayed diagnosis and treatment. In this case, though the preliminary diagnosis was established on ascitic fluid cytology, the disease progressed rapidly, leading to demise before initiating chemotherapy. Immunophenotyping and molecular studies, performed later, established a diagnosis of de novo B-cell precursor leukemia/lymphoma with MYC, BCL2 rearrangements (Double-hit lymphoma). MYC, BCL2 rearrangements are rarely reported in precursor B-lymphoma/leukemia which carry dismal prognosis. In this report, we illustrate autopsy findings of PL in an elderly gentleman who presented with ascites for evaluation.

Multisystemic Pediatric Langerhans cell histiocytosis: a comprehensive clinico-pathological and BRAF V600E mutation study at autopsy

Langerhans cell histiocytosis (LCH), a disorder of antigen-presenting cells, is the commonest disorder of the mononuclear phagocytic system. Diagnosis is always challenging due to heterogeneous clinical presentation. However, with the evolution and better understanding of its biology, many of these children are being diagnosed early and offered appropriate therapy. Despite these advances, in developing countries, an early diagnosis is still challenging due to resource constraints for specialized tests. As a result, many patients succumb to their disease. Autopsy data on LCH is notably lacking in the literature. We sought to analyze the clinical (including mutational) and morphologic features at autopsy in six proven cases of LCH. This study includes a detailed clinico-pathological and mutational analysis of 6 proven cases of LCH. Presence of BRAF V600E mutation was assessed by both Real Time PCR and Sanger sequencing. A varied spectrum of organ involvement was noted with some rare and novel morphological findings, like nodular bronchiolocentric infiltration of LCH cells, lymphovascular emboli of LCH cells, and paucity of eosinophils within the infiltrate; these features have not been described earlier. Surprisingly, all cases were negative for BRAF V600E mutation on both RQ-PCR and Sanger sequencing. The present study is perhaps the first autopsy series on LCH. This extensive autopsy analysis represents a correlation of pathological features with clinical symptoms which provides clues for a timely diagnosis and appropriate therapeutic intervention. Also, our findings hint at the low frequency of BRAF V600E mutation in our LCH patients.

Hepatic and Cardiac Iron-load in Children on Long-term Chelation with Deferiprone for Thalassemia Major

Objective: To evaluate the efficacy of prolonged deferiprone monotherapy in patients with ?-thalassemia major. Methods: This cross-sectional study included 40 patients (age range 9 to38 years) with thalassemia major receiving deferiprone for ?5 years. Serum ferritin, andmyocardial iron concentration (MIC) and liver iron concentration (LIC) assessed by T2*MRIwere recorded. Results: The patients were receiving deferiprone for a mean (SD) duration of12.1 (4.7) years. The median (IQR) dose of deferiprone was 85 (74.3, 95) mg/kg/day. TheMIC was normal or had a mild, moderate or severe elevation in 29 (72.5%), 3 (7.5%), 3(7.5%), and 5 (12.5%) patients. The LIC was normal or had a mild, moderate or severeelevation in 2 (5%), 4 (10%), 11 (27.5%) and 23 (57.5%) patients. Conclusions: The majorityof patients receiving deferiprone had a moderate/severe hepatic but normal cardiac iron load.Prolonged deferiprone monotherapy was suboptimal for hepatic iron load in the majority.

Strategic planning and designing of a hospital disaster manual in a tertiary care, teaching, research and referral institute in India / 世界急诊医学杂志（英文）

BACKGROUND:As per the "Disaster Management Act, 2005" of India, it is mandatory for government hospitals in India to prepare a disaster plan. This study aimed to prepare a disaster manual of a 1900 bed tertiary care hospital, in consultation and involvement of all concerned stakeholders. METHODS:A committee of members from hospital administration, clinical, diagnostic and supportive departments worked on an initial document prepared according to the Act and gave their inputs to frame a final disaster manual. RESULTS:The prepared departmental standard operating procedures involved 116 people (doctors and paramedical staff), and were then synchronized, in 12 committee meetings, to produce the final hospital disaster manual. CONCLUSIONS:The present disaster manual is one of the few comprehensive plans prepared by the stakeholders of a government hospital in India, who themselves form a part of the disaster response team. It also helped in co-ordinated conduction of mock drills.

The H1N1 influenza pandemic: need for solutions to ethical problems.

The rapid spread of the novel influenza virus of H1N1 swine origin led to widespread fear, panic and unrest among the public and healthcare personnel. The pandemic not only tested the world’s health preparedness, but also brought up new ethical issues which need to be addressed as soon as possible. This article highlights these issues and suggests ethical answers to the same. The main areas that require attention are the distribution of scarce resources, prioritisation of antiviral drugs and vaccines, obligations of healthcare workers, and adequate dissemination and proper communication of information related to the pandemic. It is of great importance to plan in advance how to confront these issues in an ethical manner. This is possible only if a comprehensive contingency plan is prepared with the involvement of and in consultation with all the stakeholders concerned.

Neonatal cytomegalovirus infection: diagnostic modalities available for early disease detection.

CMV is a ubiquitous virus. In India, there is high seroendemicity with almost 99% adults showing IgG antibodies. Infection or re-activation becomes important in immunocompromised host (Transplant recipients, Cancer therapy patients and patients with HIV/AIDS). Neonates form a distinctive high risk population for congenital CMV infection and suffer disastrous sequlae of the same. Neonatal infections may be congenital in nature or may be acquired after birth during first month of life via infected breast milk or due to exposure to high risk blood products. The risk for transmission of the virus to the fetus is higher in primary infected mothers than in mothers with reactivated disease. Primary CMV infections are reported in 1-4% of seronegative women during pregnancy and the risk for viral transmission to fetus is 30-40%. Reactivation of a CMV infection during pregnancy is reported in 10-30% of seropositive women and the risk of transmitting the virus is about 1-3%. The adverse outcome of congenital neonatal CMV infection includes- microcephaly (70%), intellectual impairment (60%), sensineural hearing loss (35%), choriorenitis (22%), hepatosplenomegaly (70%), jaundice (68%), thrombocytopenia (65%), low birth weight (65%), pneumonitis (2-5%) and congenital heart disease (<5%). About 5-10% of congenitally infected asymptomatic infants will have neurological problems later in life the most common of which is unilateral or bilateral sensory neural hearing loss. All immunocompromised hosts, including pre-term neonates, mount weak antibody responses (IgM), making serological detection of CMV infection in them, fallacious. Thus, it is imperative to use antigen detection methods such as quantitative PCR or PP65 Antigenaemia assays to detect CMV infection in immunocompromised host. Sakhuja et al and Minz et al have demonstrated that PP65 Antigenaemia assay is very good for diagnosing CMV disease in renal transplant recipients. The present review tends to highlight the role of newer diagnostic modalities in early CMV infection detection in neonatal population.

Acute leukemia/myelodysplastic syndrome as a sequelae of carcinoma breast: a report of five cases from north India.

A second malignant neoplasm has been found to be more frequent than might be expected from the general population rates. Therapy-related myelodysplastic syndrome and acute leukemia are dreaded long-term complications of five cases of hematological malignancies following treatment for successful breast cancer therapy (therapeutic drugs or radiotherapy). We encountered carcinoma from north India over a 7-year period from 1999 to 2005. The patients presented 2-5 years after treatment of breast carcinoma. Three patients underwent surgery and received chemoradiotherapy. One patient received chemotherapy after surgery. One patient underwent only surgery and after 3 years presented with acute myeloid leukemia and bone marrow metastasis of carcinoma of the breast. At the time of presentation, all the patients had either bicytopenia or pancytopenia. A close follow-up with complete blood cell counts of the patients who previously had carcinoma of the breast is suggested for early detection of hematological abnormalities. However, the poor prognosis, limited financial resources and poor health insurance coverage results in few patients and their family members opting for treatment.