Autopsy findings of COVID-19 in children: a systematic review and meta-analysis.

Clinical features of COVID-19 range from mild respiratory symptoms to fatal outcomes. Autopsy findings are important for understanding COVID-19-related pathophysiology and clinical manifestations. This systematic study aims to evaluate autopsy findings in paediatric cases. We searched PubMed, EMBASE, and Cochrane Database Reviews. We included studies that reported autopsy findings in children with COVID-19. A total of 11 studies (24 subjects) were included. The mean age of patients was 5.9 ± 5.7 years. Grossly, there was pericardial and pleural effusion, hepatosplenomegaly, cardiomegaly, heavy soft lung, enlarged kidney, and enlarged brain. The autopsy findings of the lungs were diffuse alveolar damage (78.3%), fibrin thrombi (43.5%), haemorrhage (30.4%), pneumonia (26%), congestion and oedema (26%), angiomatoid pattern (17.4%), and alveolar megakaryocytes (17.4%). The heart showed interstitial oedema (80%), myocardial foci of band necrosis (60%), fibrin microthrombi (60%), interstitial and perivascular inflammation (40%), and pancarditis (30%). The liver showed centrilobular congestion (60%), micro/macrovesicular steatosis (30%), and arterial/venous thrombi (20%). The kidney showed acute tubular necrosis (75%), congestion (62.5%), fibrin thrombi in glomerular capillaries (37.5%), and nephrocalcinosis, mesangial cell hyperplasia, tubular hyaline/granular casts (25% each). The spleen showed splenitis (71.4%), haemorrhage (71.4%), lymphoid hypoplasia (57.1%), and haemophagocytosis (28.6%). The brain revealed oedema (87.5%), congestion (75%), reactive microglia (62.5%), neuronal ischaemic necrosis (62.5%), meningoencephalitis (37.5%), and fibrin thrombi (25%). SARS-CoV-2 and CD68 were positive by immunohistochemistry in 85.7% and 33.3% cases, respectively. Autopsy findings of COVID-19 in children are variable in all important organs. It may help in better understanding the pathogenesis of SARS-CoV-2.

Anti-IgE therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis.

BACKGROUND: Cystic fibrosis is an autosomal recessive multisystem disorder with an approximate prevalence of 1 in 3500 live births. Allergic bronchopulmonary aspergillosis is a lung disease caused by aspergillus-induced hypersensitivity with a prevalence of 2% to 15% in people with cystic fibrosis. The mainstay of treatment includes corticosteroids and itraconazole. The treatment with corticosteroids for prolonged periods of time, or repeatedly for exacerbations of allergic bronchopulmonary aspergillosis, may lead to many adverse effects. The monoclonal anti-IgE antibody, omalizumab, has improved asthma control in severely allergic asthmatics. The drug is given as a subcutaneous injection every two to four weeks. Since allergic bronchopulmonary aspergillosis is also a condition resulting from hypersensitivity to specific allergens, as in asthma, it may be a candidate for therapy using anti-IgE antibodies. Therefore, anti-IgE therapy, using agents like omalizumab, may be a potential therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis. This is an updated version of the review. OBJECTIVES: To evaluate the efficacy and adverse effects of anti-IgE therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews. Last search: 09 September 2021. We searched two ongoing trial registries (Clinicaltrials.gov and the WHO trials platform). Date of latest search: 16 August 2021. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials comparing anti-IgE therapy to placebo or other therapies for allergic bronchopulmonary aspergillosis in people with cystic fibrosis. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed the risk of bias in the included study. They planned to perform data analysis using Review Manager. MAIN RESULTS: Only one study enrolling 14 participants was eligible for inclusion in the review. The double-blind study compared a daily dose of 600 mg omalizumab or placebo along with twice daily itraconazole and oral corticosteroids, with a maximum daily dose of 400 mg. Treatment lasted six months but the study was terminated prematurely and complete data were not available. We contacted the study investigator and were told that the study was terminated due to the inability to recruit participants into the study despite all reasonable attempts. One or more serious side effects were encountered in six out of nine (66.67%) and one out of five (20%) participants in omalizumab group and placebo group respectively. AUTHORS' CONCLUSIONS: There is lack of evidence for the efficacy and safety of anti-IgE (omalizumab) therapy in people with cystic fibrosis and allergic bronchopulmonary aspergillosis. There is a need for large prospective randomized controlled studies of anti-IgE therapy in people with cystic fibrosis and allergic bronchopulmonary aspergillosis with both clinical and laboratory outcome measures such as steroid requirement, allergic bronchopulmonary aspergillosis exacerbations and lung function.

Anti-IgE therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis.

BACKGROUND: Cystic fibrosis is an autosomal recessive multisystem disorder with an approximate prevalence of 1 in 3500 live births. Allergic bronchopulmonary aspergillosis is a lung disease caused by aspergillus-induced hypersensitivity with a prevalence of 2% to 15% in people with cystic fibrosis. The mainstay of treatment includes corticosteroids and itraconazole. The treatment with corticosteroids for prolonged periods of time, or repeatedly for exacerbations of allergic bronchopulmonary aspergillosis, may lead to many adverse effects. The monoclonal anti-IgE antibody, omalizumab, has improved asthma control in severely allergic asthmatics. The drug is given as a subcutaneous injection every two to four weeks. Since allergic bronchopulmonary aspergillosis is also a condition resulting from hypersensitivity to specific allergens, as in asthma, it may be a candidate for therapy using anti-IgE antibodies. Therefore, anti-IgE therapy, using agents like omalizumab, may be a potential therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis. This is an updated version of the review. OBJECTIVES: To evaluate the efficacy and adverse effects of anti-IgE therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews. Last search: 29 September 2017.We searched two ongoing trial registries (Clinicaltrials.gov and the WHO trials platform). Date of latest search: 24 January 2018. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials comparing anti-IgE therapy to placebo or other therapies for allergic bronchopulmonary aspergillosis in people with cystic fibrosis. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed the risk of bias in the included study. They planned to perform data analysis using Review Manager. MAIN RESULTS: Only one study enrolling 14 participants was eligible for inclusion in the review. The double-blind study compared a daily dose of 600 mg omalizumab or placebo along with twice daily itraconazole and oral corticosteroids, with a maximum daily dose of 400 mg. Treatment lasted six months but the study was terminated prematurely and complete data were not available. We contacted the study investigator and were told that the study was terminated due to the inability to recruit participants into the study despite all reasonable attempts. One or more serious side effects were encountered in six out of nine (66.67%) and one out of five (20%) participants in omalizumab group and placebo group respectively. AUTHORS' CONCLUSIONS: There is lack of evidence for the efficacy and safety of anti-IgE (omalizumab) therapy in people with cystic fibrosis and allergic bronchopulmonary aspergillosis. There is a need for large prospective randomized controlled studies of anti-IgE therapy in people with cystic fibrosis and allergic bronchopulmonary aspergillosis with both clinical and laboratory outcome measures such as steroid requirement, allergic bronchopulmonary aspergillosis exacerbations and lung function.

Anti-IgE therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis.

BACKGROUND: Cystic fibrosis is an autosomal recessive multisystem disorder with an approximate prevalence of 1 in 3500 live births. Allergic bronchopulmonary aspergillosis is a lung disease caused by aspergillus-induced hypersensitivity with a prevalence of 2% to 15% in people with cystic fibrosis. The mainstay of treatment includes corticosteroids and itraconazole. The treatment with corticosteroids for prolonged periods of time, or repeatedly for exacerbations of allergic bronchopulmonary aspergillosis, may lead to many adverse effects. The monoclonal anti-IgE antibody, omalizumab, has improved asthma control in severely allergic asthmatics. The drug is given as a subcutaneous injection every two to four weeks. Since allergic bronchopulmonary aspergillosis is also a condition resulting from hypersensitivity to specific allergens, as in asthma, it may be a candidate for therapy using anti-IgE antibodies. Therefore, anti-IgE therapy, using agents like omalizumab, may be a potential therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis. This is an updated version of the review. OBJECTIVES: To evaluate the efficacy and adverse effects of anti-IgE therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews. Last search: 27 July 2015.We searched the ongoing trial registry clinicaltrials.gov for any ongoing trials. Latest search for clinicaltrials.gov: 23 October 2015. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials comparing anti-IgE therapy to placebo or other therapies for allergic bronchopulmonary aspergillosis in people with cystic fibrosis. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed the risk of bias in the included study. They planned to perform data analysis using Review Manager. MAIN RESULTS: Only one study enrolling 14 participants was eligible for inclusion in the review. The double-blind study compared a daily dose of 600 mg omalizumab or placebo along with twice daily itraconazole and oral corticosteroids, with a maximum daily dose of 400 mg. Treatment lasted six months but the study was terminated prematurely and complete data were not available. We contacted the study investigator and were told that the study was terminated due to the inability to recruit participants into the study despite all reasonable attempts. One or more serious side effects were encountered in six out of nine (66.67%) and one out of five (20%) participants in omalizumab group and placebo group respectively. AUTHORS' CONCLUSIONS: There is lack of evidence for the efficacy and safety of anti-IgE (omalizumab) therapy in people with cystic fibrosis and allergic bronchopulmonary aspergillosis. There is a need for large prospective randomized controlled studies of anti-IgE therapy in people with cystic fibrosis and allergic bronchopulmonary aspergillosis with both clinical and laboratory outcome measures such as steroid requirement, allergic bronchopulmonary aspergillosis exacerbations and lung function.

Levalbuterol versus albuterol for acute asthma: a systematic review and meta-analysis.

BACKGROUND: Conventional albuterol is a racemic mixture of (S)-albuterol and (R)-albuterol (levalbuterol). Levalbuterol is therapeutically active component of albuterol whereas (S)-albuterol is considered inert with some unwanted effects. OBJECTIVES: To evaluate efficacy and safety of levalbuterol versus albuterol in acute asthma. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Pubmed and Cochrane databases. TRIAL ELIGIBILITY CRITERIA, PARTICIPANTS, AND INTERVENTIONS: Randomized control trials comparing levalbuterol versus albuterol for acute asthma in all age groups. DATA EXTRACTION AND RESULT SYNTHESIS: Two authors extracted data independently. Meta-analyses were performed using Review Manager Software. RESULTS: Seven trials including a total of 1625 participants fulfilled the eligibility criteria. Respiratory rate, oxygen saturation, and percentage change in FEV1 and clinical asthma score were not significantly different between the groups with mean difference (95% CI) of 0.35 (-0.81, 1.51), -0.29 (-0.68, 0.10), -28.3 (-59.95, 3.33) and -1.01 (-5.30, 3.28) respectively. There were no significant differences in side effects between groups. LIMITATIONS: Data were not available for two probable eligible trials. A few assumptions and some calculated values were used for meta-analysis. CONCLUSIONS: Levalbuterol was not superior to albuterol regarding efficacy and safety in subjects with acute asthma. We suggest that levalbuterol should not be used over albuterol for acute asthma.

Anti-IgE therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis.

BACKGROUND: Cystic fibrosis is an autosomal recessive multisystem disorder with an approximate prevalence of 1 in 3500 live births. Allergic bronchopulmonary aspergillosis is a lung disease caused by aspergillus-induced hypersensitivity with a prevalence of 2% to 15% in people with cystic fibrosis. The mainstay of treatment includes corticosteroids and itraconazole. The treatment with corticosteroids for prolonged periods of time, or repeatedly for exacerbations of allergic bronchopulmonary aspergillosis, may lead to many adverse effects. The monoclonal anti-IgE antibody, omalizumab, has improved asthma control in severely allergic asthmatics. The drug is given as a subcutaneous injection every two to four weeks. Since allergic bronchopulmonary aspergillosis is also a condition resulting from hypersensitivity to specific allergens, as in asthma, it may be a candidate for therapy using anti-IgE antibodies. Therefore, anti-IgE therapy, using agents like omalizumab, may be a potential therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis. OBJECTIVES: To evaluate the efficacy and adverse effects of anti-IgE therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews. Last search: 21 January 2013.We searched the ongoing trial registry clinicaltrials.gov for any ongoing trials. Latest search for clinicaltrials.gov: 22 February 2013. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials comparing anti-IgE therapy to placebo or other therapies for allergic bronchopulmonary aspergillosis in people with cystic fibrosis. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed the risk of bias in the included study. They planned to perform data analysis using Review Manager 5.1. MAIN RESULTS: Only one trial enrolling 14 patients was eligible for inclusion in the review. The study was terminated prematurely and complete data were not available. We contacted the study investigator and were told that the study was terminated due to the inability to recruit patients into the study despite all reasonable attempts. One or more serious side effects were encountered in six out of nine (66.67%) and one out of five (20%) patients in omalizumab group and placebo group respectively. AUTHORS' CONCLUSIONS: There is lack of evidence for the efficacy and safety of anti-IgE (omalizumab) therapy in patients with cystic fibrosis and allergic bronchopulmonary aspergillosis. There is a need for large prospective randomized controlled trials of anti-IgE therapy in people with cystic fibrosis and allergic bronchopulmonary aspergillosis with both clinical and laboratory outcome measures such as steroid requirement, allergic bronchopulmonary aspergillosis exacerbations and lung function.

UNVEILING THE REALITIES OF ANAL MELANOMA CARE IN A RESOURCE-CONSTRAINED SETTING.

A 50-year-old lady presented with complaints of a progressively increasing anal mass and occasional bleeding per rectum for the past 4 months. Examination revealed an ulcero-proliferative growth in the anal canal, whose biopsy was suggestive of malignant melanoma. Inguinal lymph nodes, though enlarged, did not show evidence of malignant deposits on FNAC. Radiological investigations revealed a T3 lesion with no evidence of nodal metastasis. She underwent local excision of the mass with uneventful intraoperative and postoperative periods. The purpose of this report is to highlight the formidable challenges encountered in diagnosing this rare tumour, with potential implications for misdiagnosis, particularly within a resource-poor setting. This case highlights the importance of resource-appropriate approaches and surgical options available in a tertiary care hospital in North India.

Morphological markers of chromosomal instability in bone marrow aspiration and trephine biopsy of acute leukemia and myelodysplastic syndrome.

The role of chromosomal instability (CI) in oncogenesis is very well described in solid tumours, but there are a lack of studies on haematology malignancy, especially with multiple morphological markers. The study aims to analyze seven morphological markers of CI- chromatin bridges (CB), multipolar mitosis (MPM), nuclear budding (NB), micronuclei (MN), nuclear heterogeneity (NH), laggards, chromatin strings (CS) in bone marrow aspirate (BMA) and biopsy of acute leukaemia (AL), and myelodysplastic syndrome (MDS). It is a retrospective cross-sectional analytical study where BMA and biopsy were reviewed for CI markers. We compared CI markers in five categories. CI markers were further correlated with clinical manifestations and outcomes of patients. The study included 54 samples of 37 patients. Overall, the median (IQR) of markers were as follows: MN 3.5 (1,7), NB 5 (1,18), MPM 1 (0,4), CB 1(0,2), Laggards 0 (0,1), and CS 2.5 (0,6). NH was noted in 65.4% of samples. All CI markers except laggards were significantly increased in B-ALL, AML, and MDS compared to other categories. Many CI markers were significantly raised with a few clinical features. The MN, MPM, Laggard, and NH markers were significantly increased in the dead patients compared to those who survived. The study, one of the first to analyze multiple CI markers, revealed that the CI markers were significantly increased in AL and MDS patients and significantly associated with clinical manifestations and outcomes. Morphology markers of CI are valuable and cost-effective in diagnostic strategy, type of malignancies, and assessing prognosis.

Fine-needle aspiration cytology finding uric acid crystals produced by Aspergillus.

Uric acid is a metabolic product of nucleic acid and protein. Hyperuricemia results from failure or lack of urate oxidase. We present a case of a 61-year-old man with a painless forearm swelling, from which uric acid crystals were found on cytology. There were also septate fungal hyphae with morphology of Aspergillus, which has the source of the uric acid. Serum uric acid levels in our patient were normal.

Indian scenario of IgA nephropathy: a systematic review and meta-analysis.

BACKGROUND: IgA nephropathy (IgAN) is most common primary glomerulopathy. There are variations in prevalence of IgAN and its clinical features in different studies from India. AIM: To summarize overall scenario of IgAN in India. METHODS: In this systematic review, studies related to IgAN and related renal disease were included. Data searched were PubMed, EMBASE, Google scholar, and Cochrane Database from inception to 31st January 2019. RESULTS: Total 49 studies (N=2480) were included: 21 studies (N=2309) of primary IgAN; 19 studies (N=21) of Secondary IgAN; four studies (N=133) of IgA vasculitis nephropathy (IgAVN); and five studies (N=17) of IgA dominant nephropathy (IgADN). Prevalence of IgAN was 16.5% in India. Age of affected persons was ranging from 27.2±16.7 to 48.6±21.3 years . Male female ratio was 1.8:1. Clinical features of Primary IgAN, IgAVN, IgADN & Secondary IgAN were microscopic hematuria (49.6%, 44.4%, 15.6% & 59.5%), macroscopic hematuria (5.1%, 0.4%,40.9%,& 35.7%), Subnephrotic proteinuria (42.1%, 29.4%, 23.2%, & 52.3%), nephrotic proteinuria (16.0%, 4.4%, 76.8%,& 47.6%), and hypertension (25.8%,18.3%, 35.5%,& 47.6%).. The 24 hours proteinuria was ranging from 2.6±1.5 to 4.7±2.3 gm/day and serum creatinine (mg/dl) was ranging from 0.9±0 to 3.5±3.9 mg/dl. Histolomorphologically, all type of IgAN showed mesangial hypercellularity and Immunofluorescence revealed IgA deposition.. CONCLUSION: The overall prevalence of primary IgAN in India was 16.5%. The subnephrotic proteinuria and microscopic hematuria were common clinical features.

Amelanotic melanoma recurrence diagnosed by fine-needle aspiration cytology: A case report.

Amelanotic melanoma is a variant of malignant melanoma. Amelanotic melanoma has similar morphology of a wide variety of epithelial and non-epithelial malignant tumours, variable cytomorphology of melanoma has been described on exfoliative and fine-needle aspiration cytology (FNAC). Aim of index study to describe FNAC of a rare case of recurrent amelanotic melanoma of right lateral knee swelling. Case: A 37-year-old male presented right lateral knee multi-nodular swelling last for 1 month with history of similar swelling 6 months back and operated. Histologically it was reported amelanotic malignant melanoma. FNAC revealed mordantly pleomorphic malignant cells predominantly plasmacytoid, plump shaped, prominent single to multiple nucleoli along with bi-nucleated and multi-nucleated tumour giant cells were also noted. Histology and immunohistochemistry (IHC) slides were reviewed and confirm the diagnosis. Concluded amelanotic melanoma has highly varied cytomorphology with multiple differential diagnosis and IHC markers are of great value for final diagnosis of it.

Vitamin D and asthma in children: A systematic review and meta-analysis of observational studies.

There is growing literature suggesting a link between Vitamin D deficiency and asthma in children, but systematic reviews are lacking. The aim of this study is to evaluate the prevalence of Vitamin D deficiency in asthmatic children and to assess the correlations of Vitamin D levels with asthma incidence, asthma control, and lung functions. PubMed, EMBASE, and Cochrane Library were searched for observational studies on asthma and Vitamin D. Two authors independently extracted data. Meta-analysis was performed using the Review Manager Software. A total of 23 (11 case-control, 5 cohort, and 7 cross-sectional) studies enrolling 13,160 participants were included in the review. Overall, Vitamin D deficiency and insufficiency were prevalent in 28.5% and 26.7% children with asthma, respectively. The mean 25-hydroxyvitamin D (25(OH)D) levels (10 studies) were significantly lower in asthmatic children as compared to nonasthmatic children with a mean difference of -9.41 (95% confidence interval [CI] -16.57, -2.25). The odds ratio of Vitamin D deficiency (eight case-control studies) was significantly higher among asthmatic children as compared to nonasthmatic children (odds ratio 3.41; 95% CI 2.04, 5.69). Correlations between Vitamin D levels and incidence of asthma, lung functions, and control of asthma had mixed results. To conclude, asthmatic children had lower 25(OH)D levels as compared to nonasthmatic children, but the correlations between 25(OH)D and asthma incidence, asthma control, and lung functions were varied. Well-designed randomized controlled trials are required to determine if children with asthma can benefit from Vitamin D supplementation.

Cost analysis and benefits of opt-out HIV testing at a tertiary care centre in northern India.

Currently, in India, the National AIDS Control Organization does not recommend HIV screening for all patients attending health care facilities. The objective of study was to evaluate cost and benefits of opt-out HIV testing at a tertiary care hospital from India. This is a retrospective cohort study of patients who had undergone HIV testing. The cost for HIV testing and cost per HIV-infected patient were determined. A total of 6512 patients (66.4% men and 905 patients younger than 14 years) with mean (SD) age of 30.3 (20.7) years were tested for HIV infection during the study period. Overall, 137 (2.1%) patients tested positive for HIV infection. Total cost for performing HIV tests during study period was Indian Rupees (INR) 649,319 (US dollar [USD] 11805.8). The estimated cost per person tested was INR 99.71 (USD1.8) and cost per HIV-infected patient identified and referred to the antiretroviral therapy centre was INR 4739.55 (USD86.2). We determined a 2.1% period prevalence estimate for HIV infection. Based on cost per HIV-infected patient identified and referred to the antiretroviral therapy centre and the burden of HIV infection, it may be cost effective to perform routine opt-out screening for HIV infection in all patients attending health care facilities in developing countries like India.

Severe and complicated Plasmodium vivax malaria in children.

Plasmodium vivax, thought to be benign until recently, has been associated with severe malaria and its complications. This retrospective study describes severe and complicated P. vivax malaria in children. It affected almost all of the organ systems and the most commonly found complications were thrombocytopenia and severe anaemia. All children with malaria, including malaria caused by P. vivax, should be monitored for such complications.