Cytomegalovirus Reactivation as a Risk Factor for All-Cause Mortality in Children Undergoing Hematopoietic Stem Cell Transplantation: Experience Over Two Decades from a Tertiary Referral Center in India.

The aim of the study was to analyse the burden of cytomegalovirus (CMV) disease in children undergoing hematopoietic stem cell transplantation (HSCT) and its correlation with all-cause mortality. We performed a retrospective study in children up to 18 years of age who underwent allogeneic HSCT between February 2002 to December 2021 in the pediatric blood and marrow transplantation unit. A total of 1035 patients were included where five hundred forty-three (52.4%) patients underwent matched family donor (MFD) HSCT, 213 (20.5%) underwent matched unrelated donor (MUD) HSCT; 279 (26.9%) underwent haploidentical HSCT (T cell replete in 213 and T cell depleted in 66 patients). CMV reactivation was documented in 258 (24.9% patients). CMV was seen in 39 (7.2%) MFD, 77 (36.1%) MUD, 106 T cell replete (49.7%) and 36 T cell depleted (54.5%) transplants. CMV reactivation was predominantly documented in those where donor and recipient were positive (D + /R +) for CMV serostatus (77%)) prior to HSCT. Overall mortality rate was significantly higher in the CMV positive group (103/258, 39.9%), as compared to the CMV negative group (152/777, 19.6%) (p value = 0.0001). CMV was the direct cause of death in 13/1035 children (1.2%). GvHD as a cause of death was found to be significantly higher among those with CMV (n = 32) as compared to those without CMV (n = 14) (35.6 versus 9%, p value = 0.0001). The incidence of CMV reactivation was noted in 25% of HSCT recipients, and predominantly in haploidentical HSCTs. CMV reactivation was shown to significantly impact all-cause mortality and there was a significantly increased risk of mortality due to GvHD among those with CMV reactivation.

Are we dealing with melioidosis under the mask of tuberculosis? - A case series.

Melioidosis is prevalent in South-East Asia. India is now become endemic to melioidosis. Melioidosis mimicks Tuberculosis (TB) and is often overlooked clinically. The spectrum of disease ranges from acute pulmonary infection to focal infection and septicemia. We report three cases of melioidosis, which was primarily suspected to be tuberculosis due to similarities in the clinical features. All patients were male and had risk factors such as type 2 diabetes mellitus as well as other risk factors such as chronic obstructive pulmonary disease (COPD), systemic hypertension, glucocorticoid therapy etc. All three patient samples were culture negative as well as negative for tests performed for the detection of tuberculosis. Conventional nested PCR targeting 251bp of 16S-23S spacer region of B. pseudomallei. was performed among individuals suspected to have extrapulmonary Tuberculosis. The presence of 251 bp was considered positive for B. pseudomallei. All three patients were treated with third generation cephalosporin and recovered due to timely diagnosis. Patients suspected for tuberculosis should be screened for B. pseudomallei, especially when AFB smear and MTB GeneXpert are negative. Often clinical samples may be culture negative for B. pseudomallei as patients are treated with antibiotics, therefore it is worthwhile performing PCR for B. pseudomallei to rule in a diagnosis of melioidosis and initiate appropriate antibiotics.

Evaluation of Characteristics and Outcomes of COVID-19 Between First Wave and Second Wave: Study From a Tertiary Cancer Care Centre, Delhi, India.

Background and objectives The second wave of coronavirus disease-19 (COVID-19) had several severe consequences in the form of rising cases, deaths, and overwhelming health infrastructure in India. However, the similarities and differences between the characteristics of the first and second waves have yet to be explained. The objectives of the study were to compare the incidence, clinical management, and mortality rates between two waves. Methods The COVID-19 data collated from Rajiv Gandhi Cancer Institute and Research Centre, Delhi between the first wave (1 April 2020 to 27 February 2021) and second wave (1 March 2021 to 30 June 2021) were evaluated in terms of incidence, the clinical course of the disease, and mortality rates. Results The number of subjects hospitalized in the first and second waves was 289 and 564, respectively. Compared to the first wave, the proportion of patients with severe disease was higher (9.7% vs. 37.8%). Several parameters such as age group, grade of disease, the reason for hospitalization, values of peripheral oxygen saturation, type of respiratory support, response to therapy, vital status, and others show statistically significant differences between the two waves (P<0.001). The mortality rate in the second wave was significantly higher (20.2% vs. 2.4%, P<0.001) than in the first wave. Interpretation and conclusions The clinical course and outcomes of COVID-19 significantly differ between the first and second waves. There is a higher incidence of hospitalized patients (66.1% vs. 33.9%) with drastically increased case fatality rate in the second wave. Disease severity in the first wave is four times lower than in the second wave. The second wave was quite devastating, which led to the shortage of critical care facilities and the loss of a significant number of lives.

COVID-19-Associated Pulmonary Mucormycosis.

COVID-19-associated mucormycosis (CAM) emerged as an epidemic in certain parts of the world amidst the global COVID-19 pandemic. While rhino-orbital mucormycosis was well reported during the pandemic, in the absence of routine diagnostic facilities including lower airway sampling, pulmonary mucormycosis was probably under-recognized. In this review, we have focused on the epidemiology and management of COVID-19-associated pulmonary mucormycosis (CAPM). CAPM is a deadly disease and mortality can be as high as 80% in the absence of early clinical suspicion and treatment. While histopathological examination of tissue for angio-invasion and cultures have remained gold standard for diagnosis, there is an increasing interest in molecular and serological methods to facilitate diagnosis in critically ill patients and often, immune-suppressed hosts who cannot readily undergo invasive sampling. Combined medical and surgical treatment offers more promise than standalone medical therapy. Maintaining adequate glycemic control and prudent use of steroids which can be a double-edged sword in COVID-19 patients are the key preventative measures. We would like to emphasize the urgent need for the development and validation of reliable biomarkers and molecular diagnostics to facilitate early diagnosis.

Lung Cancer in Non-Smokers: Clinicopathological and Survival Differences from Smokers.

Background Lung cancer in non-smokers is a clinically distinct entity based on unique epidemiology, clinicopathology, genetics, treatment response, and outcome. Data from Indian centres are scarce. The objective of this study was to compare the frequency, clinical characteristics, driver mutations, and survival of non-smoking and smoking lung cancer patients treated at a tertiary cancer centre in North India. Methodology Two years of data on 724 consecutive lung cancer patients were assessed. Clinical, demographics, smoking history, and EGFR and ALK mutation test results were collected. Descriptive and inferential statistics were applied. Survival analysis was performed using the Kaplan-Meier method. Results Non-smokers comprised 40.9% of the study sample. Non-smokers were more likely than smokers to experience disease onset at a younger age (P = 0.004) and metastasis (P < 0.001). The tumor histology showed significant differences (P < 0.001), with non-smokers more likely to be diagnosed with adenocarcinoma (77.4%), while squamous and small cell histologies were commonly found among smokers (37.6% and 13.8%, respectively). The EGFR mutation and ALK rearrangement rates in the cohort were 23.3% and 10.1%, respectively, and were more frequent in non-smoking patients. Overall, 10-year survival was 7%, with a significantly better survival rate of non-smokers than smokers (median survival time of 15.13 vs 10.17 months; P = 0.012). Conclusions About four out of 10 patients diagnosed with lung cancer at our centre were non-smokers. They were more often young, diagnosed at an advanced stage, with predominantly adenocarcinoma histology, and had a threefold higher frequency of EGFR mutations than smokers. In our cohort, non-smokers appear to be a targetable group with better survival than smokers.

Autoptic identification of disseminated mucormycosis in a young male presenting with cerebrovascular event, multi-organ dysfunction and COVID-19 infection.

Among the secondary fungal infections in Coronavirus-19 (COVID-19) infection, Aspergillosis has been reported more often than Mucormycosis. Disseminated mucormycosis is almost always a disease of severely immunosuppressed hosts. We report a young obese Asian male who was admitted with an acute anterior cerebral artery (ACA) territory infarct and severe COVID-19 pneumonitis to the intensive care unit (ICU). He had a complicated stay with recurrent episodes of vasoplegic shock and multi-organ dysfunction. At autopsy, he was confirmed to have disseminated mucormycosis. We believe this to be the first documented case of disseminated mucormycosis in an immunocompetent host with COVID-19 infection. The lack of sensitive non-invasive modalities and biomarkers to diagnose mucormycosis, along with the extremely high mortality in untreated cases, present a unique challenge to clinicians dealing with critically ill patients with COVID-19.

COVID-19 mortality in cancer patients: a report from a tertiary cancer centre in India.

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.

Clinical and Genetic Spectrum of a Large Cohort of Patients With Leukocyte Adhesion Deficiency Type 1 and 3: A Multicentric Study From India.

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 ITGß2 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 ITGß2 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.

Clinical, Immunological, and Molecular Findings in 57 Patients With Severe Combined Immunodeficiency (SCID) From India.

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).

Vitamin D Deficiency as a Factor Influencing Asthma Control in Children.

OBJECTIVE: To study the association between asthma control and serum 25OH Vitamin D levels in children with moderate persistent asthma on preventer therapy. METHODS: Children aged 6-18 years, with moderate persistent asthma, on preventer therapy for ≥2 months were included. Control was categorized as good, partial or poor as per GINA guidelines. Serum 25 (OH) Vitamin D levels were measured and their relationship with the level of control was studied. RESULTS: Out of 50 children enrolled, 22 had well-controlled asthma, and 21 had partially controlled asthma. Vitamin D was deficient in 30 children and insufficient in 18 children. Children with vitamin D deficiency had significantly less well-controlled asthma as compared to those with insufficient or sufficient levels of 25 (OH) vitamin D (13.3% vs 88.9% vs 100%). CONCLUSIONS: Vitamin D deficiency is associated with suboptimal asthma control.

Streptococcal Toxic Shock syndrome.

Streptococcal Toxic Shock syndrome (STSS) is a serious complication caused by exotoxins of Group A Streptococcus (GAS). It presents with fulminant shock and rash, is rapidly progressive with Multi-Organ Dysfunction Syndrome (MODS) and requires aggressive therapy with fluids, antibiotics and source control.

Heterogeneous photocatalytic degradation of methanol over uranyl-anchored nanoporous MCM-41 and MCM-48.

The vapor-phase photodegradation of methanol to carbon dioxide was carried out over uranyl-anchored nanoporous MCM-41 and MCM-48 hosts (designated as UO2(2+)/MCM-41 and UO2(2+)/MCM-48, respectively) under simulated light and ambient conditions. Preliminary results indicate that the photoactivity of the latter is considerably decreased as compared to the former due to the presence of a smaller fraction of photoactive uranyl (UO2(2+)) ions in UO2(2+)/MCM-48.