Background Cancer patients, especially those receiving cytotoxic therapy, are assumed to have a higher probability of death from COVID-19. We have conducted this study to identify the Case Fatality Rate (CFR) in cancer patients with COVID-19 and have explored the relationship of various clinical factors to mortality in our patient cohort. Methods All confirmed cancer cases presented to the hospital from June 8 to August 20, 2020, and developed symptoms/radiological features suspicious of COVID-19 were tested by Real-time polymerase chain reaction assay and/or cartridge-based nucleic acid amplification test from a combination of naso-oropharyngeal swab for SARS-CoV-2. Clinical data, treatment details, and outcomes were assessed from the medical records. Results Of the total 3,101 cancer patients admitted to the hospital, 1,088 patients were tested and 186 patients were positive for SARS-CoV-2. The CFR in the cohort was 27/186 (14.52%). Univariate analysis showed that the risk of death was significantly associated with the presence of any comorbidity (OR: 2.68; (95% CI [1.13–6.32]); P = 0.025), multiple comorbidities (OR: 3.01; (95% CI [1.02–9.07]); P = 0.047 for multiple vs. single), and the severity of COVID-19 presentation (OR: 27.48; (95% CI [5.34–141.49]); P < 0.001 for severe vs. not severe symptoms). Among all comorbidities, diabetes (OR: 3.31; (95% CI [1.35–8.09]); P = 0.009) and cardiovascular diseases (OR: 3.77; (95% CI [1.02–13.91]); P = 0.046) were significant risk factors for death. Anticancer treatments including chemotherapy, surgery, radiotherapy, targeted therapy, and immunotherapy administered within a month before the onset of COVID-19 symptoms had no significant effect on mortality. Conclusion To the best of our knowledge, this is the first study from India reporting the CFR, clinical associations, and risk factors for mortality in SARS-CoV-2 infected cancer patients. Our study shows that the frequency of COVID-19 in cancer patients is high. Recent anticancer therapies are not associated with mortality. Pre-existing comorbidities, especially diabetes, multiple comorbidities, and severe symptoms at presentation are significantly linked with COVID-19 related death in the cohort.
Tuberculosis and P. carinii are the most common nonpyogenic infections in the first year after transplantation in developing countries. An aggressive search for tubercle bacilli should be made using bronchoscopy and examination of BAL fluid in patients not responding to a short trial of antibiotics. A four-drug regime without rifampicin given for 18 months is effective for pulmonary tuberculosis in patients on cyclosporine. We recommend routine prophylactic use of one single-strength tablet of cotrimoxazole daily for at least six months after transplantation.
Severe combined immunodeficiency (SCID) represents one of the most severe forms of primary immunodeficiency (PID) disorders characterized by impaired cellular and humoral immune responses. Here, we report the clinical, immunological, and molecular findings in 57 patients diagnosed with SCID from India. Majority of our patients (89%) presented within 6 months of age. The most common clinical manifestations observed were recurrent pneumonia (66%), failure to thrive (60%), chronic diarrhea (35%), gastrointestinal infection (21%), and oral candidiasis (21%). Hematopoietic Stem Cell Transplantation (HSCT) is the only curative therapy available for treating these patients. Four patients underwent HSCT in our cohort but had a poor survival outcome. Lymphopenia (absolute lymphocyte counts/μL <2,500) was noted in 63% of the patients. Based on immunophenotypic pattern, majority of the cases were T−B− SCID (39%) followed by T−B+ SCID (28%). MHC class II deficiency accounted for 10.5% of our patient group. A total of 49 patients were molecularly characterized in this study and 32 novel variants were identified in our cohort. The spectrum of genetic defects in our cohort revealed a wide genetic heterogeneity with the major genetic cause being RAG1/2 gene defect (n = 12) followed by IL2RG (n = 9) and JAK3 defects (n = 9). Rare forms of SCID like Purine nucleoside phosphorylase (PNP) deficiency, reticular dysgenesis, DNA-Protein Kinase (DNA-PKcs) deficiency, six cases of MHC class II deficiency and two ZAP70 deficiency were also identified in our cohort. Fourteen percent of the defects still remained uncharacterized despite the application of next generation sequencing. With the exception of MHC class II deficiency and ZAP70 deficiency, all SCID patients had extremely low T cell receptor excision (TRECs) (<18 copies/μL).
Leukocyte adhesion deficiency (LAD) syndrome is a group of inborn errors of immunity characterized by a defect in the cascade of the activation and adhesion leading to the failure of leukocyte to migrate to the site of tissue injury. Three different types of LAD have been described. The most common subtype is LAD type 1 (LAD1) caused due to defects in the ITGβ2 gene. LAD type 2 (LAD2) is caused by mutations in the SLC35C1 gene leading to a generalized loss of expression of fucosylated glycans on the cell surface and LAD type 3 (LAD3) is caused by mutations in the FERMT3 gene resulting in platelet function defects along with immunodeficiency. There is a paucity of data available from India on LAD syndromes. The present study is a retrospective analysis of patients with LAD collated from 28 different centers across India. For LAD1, the diagnosis was based on clinical features and flow cytometric expression of CD18 on peripheral blood leukocytes and molecular confirmation by Sanger sequencing. For patients with LAD3 diagnosis was largely based on clinical manifestations and identification of the pathogenic mutation in the FERMT3 gene by next-generation Sequencing. Of the total 132 cases diagnosed with LAD, 127 were LAD1 and 5 were LAD3. The majority of our patients (83%) had CD18 expression less than 2% on neutrophils (LAD1°) and presented within the first three months of life with omphalitis, skin and soft tissue infections, delayed umbilical cord detachment, otitis media, and sepsis. The patients with CD18 expression of more than 30% (LAD1+) presented later in life with skin ulcers being the commonest manifestation. Bleeding manifestations were common in patients with LAD3. Persistent neutrophilic leukocytosis was the characteristic finding in all patients. 35 novel mutations were detected in the ITGβ2 gene, and 4 novel mutations were detected in the FERMT3 gene. The study thus presents one of the largest cohorts of patients from India with LAD, focusing on clinical features, immunological characteristics, and molecular spectrum.
MTX 25mg is an effective dose as monotherapy for the treatment of severe psoriasis, whereas the 10mg dose is slow to act and less effective, but has a less severe side-effect profile.
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