Utility of Itraconazole in Combination with Liposomal Amphotericin B in Rhizopus oryzae Associated Mucormycosis-An Exploratory Study.

BACKGROUND: During the COVID-19 pandemic-associated mucor epidemic, acute antifungal drug shortage necessitated the exploration of other antifungals based on culture sensitivity. Itraconazole is a cheap, safe, and effective antifungal in sensitive cases. METHODOLOGY: We enrolled itraconazole-sensitive COVID-19-associated mucormycosis during the mucormycosis pandemic. After the intensive phase course of liposomal amphotericin B, Itraconazole was offered in susceptible cases during the maintenance phase along with standard of care. These patients were clinically and radiologically followed for 6 months. RESULTS: We enrolled 14 patients (Male: Female-11:3) of Rhino-orbito-cerebral mucormycosis (ROCM) which included 12 diabetics. All patients had facial swelling, orbital swelling, visual impairment, and headache. MRI showed involvement of bilateral sinus (10/14), orbital extension (13/14), cavernous sinus (5/14), cerebral part of the internal carotid artery (3/14), and brain infarcts (4/14). All 14 patients showed sensitivity to Itraconazole with 12 having minimum inhibitory concentration (MIC) ≤ 1 µg/ml and 2 having MIC ≤ 2 µg/ml. Follow-up at 6 months showed clinical improvement in the majority (11/14) and radiological improvement in six out of seven scanned patients. CONCLUSION: Our study shows the potential therapeutic role of oral Itraconazole in ROCM.

T-cell dysfunction as a potential contributing factor in post-COVID-19 mucormycosis.

BACKGROUND: The second wave of COVID-19 in India was followed by large number of mucormycosis cases. Indiscriminate use of immunosuppressive drugs, underlying diseases such as diabetes, cancers, or autoimmune diseases was thought to be the cause. However, the mortality was not as high as that seen in non-COVID mucormycosis. OBJECTIVE: To study the detailed characteristics of T-cells for evaluating the underlying differences in the T-cell immune dysfunction in post-COVID and non-COVID mucor patients. MATERIAL AND METHOD: The study included histopathologically confirmed cases of mucor (13 post-COVID, 13 non-COVID) and 15 healthy individuals (HI). Expression of T-cell activation (CD44, HLADR, CD69, CD38) and exhaustion (CTLA, PD-1, LAG-3 and TIM-3) markers was evaluated by flow cytometry. RESULTS: All cases showed significant depletion of T-cells compared to HI. Both post-COVID and non-COVID groups showed increased activation and exhaustion as compared to HI. Non-COVID mucor group showed significant activation of CD4+ T cells for HLADR and CD38 (p = .025, p = .054) and marked T-cell exhaustion in form of expression of LAG-3 on both CD4+ T and CD8+ T cells in comparison with post-COVID patients (p = .011, p = .036). Additionally, co-expression of PD-1 & LAG-3 and LAG-3 & TIM-3 on CD8+ T cells was statistically significant in non-COVID mucor patients (p = .016, p = .027). CONCLUSION: Immunosuppression in non-COVID mucor showed pronounced exhaustion of T-cells in comparison to post-COVID mucor cases implicating T-cell immune dysfunction is much more severe in non-COVID mucor which are in a state of continuous activation followed by extreme exhaustion leading to poorer outcome.

DABCO-based chiral ionic liquids as recoverable and reusable organocatalyst for asymmetric Diels-Alder reaction.

New DABCO-based chiral ionic liquids were synthesized and evaluated in asymmetric Diels-Alder reaction of cyclopentadiene with α,ß-unsaturated aldehydes or 4-phenyl-3-buten-2-one. Chiral ionic liquid of modified MacMillan catalyst having a DABCO cation and hexafluorophosphate anion acts as organocatalyst (5 mol%) for the Diels-Alder reaction of crotonaldehyde and cyclopentadiene producing 98% of the product and 87% ee (endo) in CH3 CN/H2 O (95/5) at 25°C in 2 h. The scope and limitations of the catalysis were also studied by using cyclopentadiene and α,ß-unsaturated aldehydes, and the Diels-Alder products were obtained in 18%-92% yields with 68%-93% ee. The catalyst was recycled and reused up to 6 cycles with a slight drop in ee and conversion of the product.

Cytomegalovirus Coinfection in Critically Ill Patients with Novel Coronavirus-2019 Disease: Pathogens or Spectators?

Coronavirus disease-2019 (COVID-19) pandemic is raging all over the world. As we are delving more into management of COVID-19, certain new challenges are emerging. One of these is emergence or reactivation of viral infections belonging to Herpesviridae family, especially cytomegalovirus (CMV). Although we have come across the threat of fungal and resistant bacterial infections, experience regarding reactivation or coinfection with concomitant viral infections like CMV during the COVID pandemic is still limited. Whether CMV is a bystander or pathogen is difficult to say categorically and needs further research. In this case series, we intend to describe three patients of COVID-19 with CMV coinfections. To our knowledge, this is the first case series from India. How to cite this article: Siddiqui SS, Chatterjee S, Yadav A, Rai N, Agrawal A, Gurjar M, et al. Cytomegalovirus Coinfection in Critically Ill Patients with Novel Coronavirus-2019 Disease: Pathogens or Spectators? Indian J Crit Care Med 2022;26(3):376-380.

Mortality among adult hospitalized patients during the first wave and second wave of COVID-19 pandemic at a tertiary care center in India.

The similarities and differences between the mortality patterns of the two waves in India remain largely unknown. This was a retrospective study of medical records conducted in the COVID data center of our hospital This study analyzed data of patients who died in the month of August, 2020 to October 2020 (one month before and after the peak of first wave i.e., 16th September, 2020) and April 2021 to June 2021 (one month before and after the peak of second wave i.e., 6th May, 2021), corresponding to an equal part of the pandemic during first (2020) and second (2021) wave. Out of 1893 patients in the study, 764 patients were admitted during the first wave and 1129 patients during the second wave of pandemic. In total, 420 patients died during the entire study period. Of those, 147 (35%) deaths occurred during the first wave and 273 (65%) during the second wave, reflecting a case fatality rate (CFR) of 19.2% during the first wave and a CFR of 24.18%. There were no significant differences in the age group, gender, presenting complaints, duration of stay and comorbidities. However, the deceased COVID-19 patients had an increase in case fatality rate, average duration of symptoms from onset to hospital admission (DOSHA) and a major shift from MODS to ARDS being the cause of death during the second wave of pandemic. This study demonstrates increased CFR, average DOSHA and a paradigm shift to ARDS as cause of mortality during the second peak of the pandemic. It is necessary to remain vigilant of newer COVID-19 variants of concern, follow COVID-19 appropriate behaviors and keep emphasizing on care of high-risk groups including patients with comorbidities and elderly population to prevent mortality.

Chiral Imidazolidin-4-one with catalytic amount of Dicationic ionic liquid act as a recoverable and reusable Organocatalyst for asymmetric Diels-Alder reaction.

Imidazolidin-4-one is used as a recoverable organocatalyst for the asymmetric Diels-Alder reaction in the presence of catalytic amount of dicationic ionic liquid and trifluoroacetic acid as a co-catalyst. The Diels-Alder reaction between model substrate cyclopentadiene and crotonaldehyde gave the product in 95% conversion and 87% ee of the endo-product. The catalyst was shown better reusability when the 20 mol% of dicationic ionic liquid was used and catalyst was reused upto 5 cycles, conversion remains upto 3 recycles but ee of endo-9 was slightly droped.

Swelling and infusion of tea in tea bags.

The present study deals with swelling and infusion kinetics of tea granules in tea bags. The swelling and infusion kinetics of tea bags differing in tea loading and tea bag shapes were compared with loose tea. Increment in temperature and dipping frequency of tea bag in hot water increased the infusion kinetics of tea bags. Reduction in particle size enhanced the swelling and infusion kinetics of tea in a tea bag. The effects of tea particle size, tea bag dipping rate, loading of tea granules in tea bag and tea bag shapes on infusion kinetics were investigated. Increase in tea loading in tea bags resulted in reduced infusion kinetics. Double chambered tea bag showed the highest swelling (30%) and infusion kinetics (8.30% Gallic acid equivalence) while single chambered tea bags showed the lowest kinetics, amongst the various bags studied. The swelling and infusion kinetics of loose tea was always faster and higher than that of tea bags. It was found that overall effect of percentage filling of tea granules and height of tea bed in a tea bag affects tea infusion kinetics the most. Weibull model was found to be in good agreement with the swelling data.

Swelling kinetics of tea in hot water.

In this study, the swelling kinetics of individual tea particles as well as bed of tea granules were investigated for different types of teas. The swelling experiments involved image analysis and volume measurements of tea particles. Each individual particle shows different swelling characteristics. Separating funnels and cylindrical columns of varying sizes were used to study the changes in volume of tea bed. Swelling in separating funnel was observed to be more than that in column. The effect of temperature, particle size, bed height and vessel diameter were investigated. The extent as well as the rate of swelling is found to increase with rise in temperature (60 to 80 °C) and reduction in particle size. A decrease in swelling is observed with increase in bed height as well as decrease in vessel diameter and vice a versa. About 70 to 75 % swelling occurs in the first 40 to 45 s. Two empirical models viz. Weibull and Peleg were used to fit the experimental data. The rate parameters obtained for a sample T5 at different temperatures were in the range of 0.012 to 0.016. The volume changes of all the teas were compared with their elution behavior, by measuring the absorbance of a diluted sample of brew at 272 nm. The activation energies for the process of tea swelling calculated for T1 (1.2 mm), T5 (2.2 mm) and T5 (0.72 mm) were 14.156, 8.37 and 13.42 kJ/mol respectively.

Targeting the Wnt/ß-catenin cascade in osteosarcoma: The potential of ncRNAs as biomarkers and therapeutics.

Osteosarcoma (OS) is a bone cancer which stems from several sources and presents with diverse clinical features, making evaluation and treatment difficult. Chemotherapy tolerance and restricted treatment regimens hinder progress in survival rates, requiring new and creative therapeutic strategies. The Wnt/ß-catenin system has been recognised as an essential driver of OS development, providing potential avenues for therapy. Non-coding RNAs (ncRNAs), such as circular RNAs (circRNAs), long non-coding RNAs (lncRNAs), and microRNAs (miRNAs), are essential in modulating the Wnt/ß-catenin cascade in OS. MiRNAs control the system by targeting vital elements, while lncRNAs and circRNAs interact with system genes, impacting OS growth and advancement. This paper thoroughly analyses the intricate interplay between ncRNAs and the Wnt/ß-catenin cascade in OS. We examine how uncontrolled levels of miRNAs, lncRNAs, and circRNAs lead to an abnormal Wnt/ß-catenin network, which elevates the development, spread, and susceptibility to the treatment of OS. We emphasise the potential of ncRNAs as diagnostic indicators and avenues for treatment in OS care. The review offers valuable insights for academics and clinicians studying OS aetiology and creating new treatment techniques for the ncRNA-Wnt/ß-catenin cascade. Utilising the oversight roles of ncRNAs in the Wnt/ß-catenin system shows potential for enhancing the outcomes of patients and progressing precision medicine in OS therapy.

Humoral and cellular immune response in patients of liver cirrhosis and immunocompetent recipient of ChAdOx1nCoV-19 Vaccine (Covishield).

Despite the effectiveness of COVID-19 vaccination in reducing the severity of the disease, the demand for booster is increasing in vulnerable populations like elderly and immunocompromised individuals especially with each new wave of COVID-19 in different countries. There is limited data on the sustained immunity against COVID-19 in patients with liver cirrhosis. The study was aimed to compare the T cell and humoral immune response after 1 year of ChAdOx1nCoV-19 Vaccine in patients with liver cirrhosis and healthy health care workers (HCW). This was a prospective observational study including 36 HCW, 19 liver cirrhosis patients and 10 unvaccinated individuals. Anti-SARS-CoV-2S antibody, neutralizing antibody and memory T cell subsets were evaluated by ELISA and flow cytometry, respectively, in all three groups after 1 year of initial vaccination. Compared to HCW and unvaccinated individuals, liver cirrhosis patients had significantly depleted T cells, although CD4:CD8 + T cell ratio was normal. Both cirrhotic patients and HCW developed memory T cell subset [effector memory RA (P = 0.141, P < 0.001), effector memory (P < 0.001, P < 0.001), central memory (P < 0.001, P < 0.01), stem cell memory (P = 0.009, P = 0.08) and naïve (P < 0.001, P = 0.02)] compared to unvaccinated unexposed individuals of CD4 + T and CD8 + T, respectively. However, among HCW and cirrhotic group no difference was noted on central memory and stem cell memory cells on T cells. Patients with liver cirrhosis developed comparable memory T cells after vaccination which can evoke sustainable immune response on reinfection. Therefore, additional vaccine doses may not be necessary for cirrhosis patients.

Prevalence of High and Moderate Risk of Liver Fibrosis Among Patients With Diabetes at a Noncommunicable Diseases (NCD) Clinic in a Primary Healthcare Center in Northern India.

Background Diabetes is a known entity that contributes to increased incidence and progress of liver fibrosis. Despite the integration of nonalcoholic fatty liver disease (NAFLD) into the NP-NCD program (National Programme for Prevention and Control of Cancer, Diabetes, Cardiovascular Diseases, and Stroke [NPCDCS]), screening individuals in primary healthcare settings for liver fibrosis remains uncommon. The objective of this study was to determine the prevalence of the risk of liver fibrosis in individuals with diabetes. Methodology The secondary data analysis was conducted among patients with diabetes attending the noncommunicable diseases (NCD) clinic at the Primary Health Center (PHC) Najafgarh, Delhi, from January 2023 to June 2023. We used the Fibrosis-4 (FIB-4) score to assess the risk of liver fibrosis. The data analysis was carried out using Stata 17.0 software (StataCorp, College Station, TX). Results Out of 394 individuals screened, 158 (39.5%) were male and 236 (60.5%) were female. Among the study participants, 64.9% (95% confidence interval [CI] 60.0%-69.7%) were of low risk, 30.5% (95% CI 25.9%-35.3%) were of intermediate risk, and 4.6% (95% CI 2.7%-7.1%) were of high risk of developing liver fibrosis based on FIB-4 scoring. The increased risk was associated with increased age, duration of diabetes, and dyslipidemia. Conclusions The prevalence of high risk of liver fibrosis among patients with diabetes was 4.6% (95% CI 2.7%-7.1%), whereas an intermediate risk of developing liver fibrosis was observed in 30.5%. The study advocates integrating these screening tools into primary healthcare settings, alleviating the strain on larger healthcare facilities. It also underscores the importance of early detection and management of liver fibrosis in patients with diabetes.

Study of Hemato-morphological Features in Neuroblastoma Infiltrating Marrow.

Objective Neuroblastoma typically affects children within the first 5 years of life and accounts for 10% of all pediatric malignancies. Neuroblastoma at onset may manifest as a localized or metastatic illness. The aim of this study was to identify hematomorphological features in neuroblastoma infiltrating marrow as well as to ascertain the prevalence of bone marrow infiltration in neuroblastoma. Materials and Methods This retrospective study included newly diagnosed 79 cases of neuroblastoma, which were referred for bone marrow examination for the staging of the disease. Medical records were retrieved to acquire hematomorphological findings of peripheral blood and bone marrow smears. Statistical Package for Social Sciences, IBM Inc., USA, version 21.0 was used to analyze the data. Results The interquartile age range of neuroblastoma cases was 24.0 to 72.0 months (median = 48 months) with a male to female ratio of 2.7:1. Also, 55.6% (44/79) of cases in the study population showed evidence of marrow infiltration. The bone marrow infiltration was significantly linked to thrombocytopenia ( p = 0.043) and nucleated red blood cells ( p = 0.003) in peripheral blood. The bone marrow smears of cases with infiltration showed a significant shift to the left in the myeloid series ( p = 0.001) and an increased number of erythroid cells ( p = 0.001). Conclusion For neuroblastoma patients, a diligent, exhaustive search for infiltrating cells in bone marrow is advised if thrombocytopenia or nucleated red blood cells are identified on a peripheral blood smear and bone marrow smears showed myeloid left shift with an increased number of erythroid cells.

Utility of bone marrow examination in retinoblastoma and their correlation with hematological features.

Retinoblastoma makes up about 3% of all childhood malignancies. The frequency of metastatic retinoblastoma ranges from 4.8 to 11%. Assessing the bone marrow status of newly diagnosed patients is crucial because of the advantages of autologous bone marrow transplants for high-risk patients. This study aimed to determine the utility of bone marrow examination in cases of retinoblastoma and its correlation with hematological findings. This retrospective study was conducted at the Department of Pathology, King George's Medical University, Lucknow, India. A total of 34 cases of retinoblastoma with bone marrow examination were included in the study. Bone marrow infiltration was present in 17.65% (6/34) cases of retinoblastoma. Bone marrow aspirate myelogram showed that marrow metastasis in retinoblastoma was significantly linked with a reduced percentage of total myeloid cells (p=0.001) and segmented cells (p=0.006). The present study demonstrated that 15% (3/20) of retinoblastoma patients previously classified as nonmetastatic before bone marrow examination (stages I to III based on histology, imaging, and bone scan) had bone marrow metastases following bone marrow examination and were upgraded to stage IV. To conclude, a diligent and exhaustive search for metastatic cells in bone marrow is advised if the myelogram shows a reduced percentage of total myeloid and segmented cells. All stage II and stage III cases of retinoblastoma must undergo bone marrow examination for early metastasis detection, as it may result in an upgrade to stage IV disease, impacting the prognosis and necessitating distinct treatment modalities.

Early and Effective Diagnosis of Sepsis Using Flow Cytometry.

Objective Sepsis is a major global health issue due to its high death and morbidity rates. To avoid the negative effects of sepsis and decrease mortality, it is vital to diagnose and treat it as soon as possible. Blood cultures can take up to 2 days to give result, and they are not always reliable. According to recent studies, neutrophil CD64 expression might be a sensitive and specific option for assessing sepsis. This study aimed to evaluate the diagnostic performance of a flow cytometry analysis for the expression of neutrophil CD64 in sepsis and its comparison with other standard tests in a tertiary care center. Materials and Methods Prospective analysis on 40 blood samples from suspected sepsis patients admitted to intensive care units with criteria for the systemic inflammatory response syndrome on presentation was performed for expression of neutrophil CD64, C-reactive protein, procalcitonin, and complete blood count. Ten healthy volunteers were also enrolled in this prospective study. The laboratory results were compared in different groups. Results The neutrophil CD64 had the highest diagnostic value to differentiate between patients of sepsis and nonsepsis groups with a sensitivity of 100% (95% confidence interval [CI]: 77.19-100%) and 100% (95% CI: 55.32-86.83%); specificity of 90.00% (95% CI: 59.58-99.49%) and 87.24% (95% CI: 66.69-99.61%); and likelihood ratio of 10.00 and 7.84, respectively. Conclusion The neutrophil CD64 expression provides a more sensitive, specific, and novel marker for the early detection of sepsis in critically ill patients.

Interleukin-6 and interleukin-8 levels in children with aplastic anemia and its correlation with disease severity and response to immunosuppressive therapy.

Background: Aplastic anemia (AA) is an uncommon condition characterized by pancytopenia and hypocellular bone marrow. Interleukin (IL)-6 and IL-8 have been shown to inhibit myelopoiesis and are major mediators of tissue damage. The primary goal of this study was to determine the IL-6 and IL-8 levels in children with AA, as well as their relationship to illness severity and immunosuppressive medication response. Materials and Methods: The IL-6 and IL-8 levels were tested in 50 children aged 3-18 years who had AA. As controls, 50 healthy age and sex matched individuals were used. A sandwich enzyme-linked immunosorbent assay kit (solid-phase) was used to measure IL-6 and IL-8 levels quantitatively. The concentrations of IL-6 and IL-8 in pg/mL were used to represent the results. Immunosuppressive medication was given to the patients in accordance with the British Committee for Standards in Haematology Guidelines 2009. Results: The patients' average age was 11.3 ± 3.7 years. Patients with AA had significantly higher IL-6 and IL-8 levels than controls (278.88 ± 216.03 vs. 4.51 ± 3.26; P < 0.001) and (120.28 ± 94.98 vs. 1.79 ± 0.78; P < 0.001), respectively. The IL-6 and IL-8 levels were also investigated with respect to AA severity, with statistically significant differences (P < 0.01) between different grading strata. Patients with very severe AA (VSAA) had the highest IL-6 levels (499.52 ± 66.19), followed by severe AA (SAA) (201.28 ± 157.77) and non-SAA (NSAA) (22.62 ± 14.63). For IL-8 levels, a similar trend (P < 0.01) was detected, with values of 209.81 ± 38.85, 92.12 ± 78.0, and 9.29 ± 10.68 for VSAA, SAA, and NSAA, respectively. After 6 months of immunosuppressive treatment (IST), mean levels of IL-6 and IL-8 in responders and nonresponders were again assessed. The mean IL-6 level in the responders' group (46.50 ± 45.41) was significantly lower, when compared to the nonresponders' group (145.76 ± 116.32) (P < 0.001). Similarly, the mean IL-8 level in the responder's group (33.57 ± 27.14) was significantly lower, compared to the nonresponder's group (97.49 ± 69.00) (P < 0.001). Conclusions: Children with AA had higher IL-6 and IL-8 levels than normal age- and sex-matched controls. Increased levels were linked to the severity of the condition, suggesting that IL may have a role in AA. IL levels can be monitored in AA patients during IST, which can assist in predicting response to IST.

Résumé Contexte: L'anémie aplastique (AA) est une affection peu fréquente caractérisée par une pancytopénie et une moelle osseuse hypocellulaire. Il a été démontré que l'interleukine (IL)-6 et l'IL-8 inhibent la myélopoïèse et sont des médiateurs majeurs des lésions tissulaires. L'objectif principal de cette étude était de déterminer les niveaux d'IL-6 et d'IL-8 chez les enfants atteints d'AA, ainsi que leur relation avec la gravité de la maladie et la réponse aux médicaments immunosuppresseurs. Matériel et méthodes: Les niveaux d'IL-6 et d'IL-8 ont été testés chez 50 enfants âgés de 3 à 18 ans atteints d'AA. 50 témoins sains appariés par l'âge et le sexe ont été utilisés. Un kit de dosage immuno-enzymatique en sandwich (phase solide) a été utilisé pour mesurer quantitativement les niveaux d'IL-6 et d'IL-8. de manière quantitative. Les concentrations d'IL-6 et d'IL-8 en pg/mL ont été utilisées pour représenter les résultats. Des médicaments immunosuppresseurs ont été administrés aux patients conformément aux directives 2009 du British Committee for Standards in Haematology. Résultats: L'âge moyen des patients était de 11,3 ± 3,7 ans. Les patients atteints d'AA présentaient des taux d'IL-6 et d'IL-8 significativement plus élevés que les témoins (278,88 ± 216,03 contre 4,51 ± 3,26 ; P < 0,001) et (120,28 ± 94,98 contre 1,79 ± 0,78 ; P < 0,001), respectivement. Les taux d'IL-6 et d'IL-8 ont également été étudiés en fonction de la gravité de l'AA, avec des différences statistiquement significatives (P < 0,01) entre les différentes strates de classement. Les patients présentant une AA très sévère (VSAA) avaient les taux d'IL-6 les plus élevés (499,52 ± 66,19), suivis par les patients atteints d'AA sévère (SAA) (201,28 ± 157,77) et les patients non-SAA (NSAA) (22,62 ± 14,63). Pour les niveaux d'IL-8, une tendance similaire (P < 0,01) a été détectée, avec des valeurs de 209,81 ± 38,85, 92,12 ± 78,0, et 9,29 ± 10,68 pour les VSAA, SAA et NSAA, respectivement. Après 6 mois de traitement immunosuppresseur traitement immunosuppresseur (IST), les niveaux moyens d'IL-6 et d'IL-8 chez les répondeurs et les non-répondeurs ont été à nouveau évalués. Le taux moyen d'IL-6 dans le groupe des répondeurs (46,50 ± 45,41) était significativement plus faible, par rapport au groupe des non-répondeurs (145,76 ± 116,32) (P < 0,001). De même, le niveau moyen d'IL-8 dans le groupe des répondeurs (33,57 ± 27,14) était significativement plus faible que dans le groupe des non-répondeurs (97,49 ± 69,00) (P < 0,001). Conclusions: Les enfants atteints d'AA présentaient des niveaux d'IL-6 et d'IL-8 plus élevés que les témoins normaux appariés selon l'âge et le sexe. L'augmentation des taux était liée à la gravité de l'affection, suggérant que l'IL pourrait jouer un rôle dans l'AA. Les niveaux d'IL peuvent être surveillés chez les patients atteints d'AA pendant l'IST, ce qui peut aider à prédire la réponse à l'IST. Mots-clés: Anémie aplastique, traitement immunosuppresseur, interleukine-6, interleukine-8.

Severe COVID-19-associated hyperinflammatory syndrome versus classic hemophagocytic lymphohistiocytosis: similarities, differences, and the way forward.

The hyperinflammatory immune response in severe COVID-19 infection shares features with secondary hemophagocytic lymphohistiocytosis (sHLH) in the form of fever, cytopenia, elevated inflammatory markers, and high mortality. There are contrasting opinions regarding utility of HLH 2004 or HScore in the diagnosis of severe COVID-19-related hyperinflammatory syndrome (COVID-HIS). This was a retrospective study of 47 patients of severe COVID-19 infection, suspected to have COVID-HIS and 22 patients of sHLH to other illnesses, to evaluate the diagnostic utility and limitations of HLH 2004 and/or HScore in context to COVID-HIS and to also evaluate the utility of Temple criteria for predicting severity and outcome in COVID-HIS. Clinical findings, hematological, and biochemical parameters along with the predictor of mortality were compared between two groups. Only 6.4% (3/47) of cases fulfilled ≥5/8 HLH 2004 criteria and only 40.52% (19/47) of patients showed HScore >169 in COVID-HIS group. 65.9% (31/47) satisfied the Temple criteria in COVID-HIS as compared with 40.9% (9/22) in the non-COVID group (p = 0.04). Serum ferritin (p = 0.02), lactate dehydrogenase (p = 0.02), direct bilirubin (p = 0.02), and C-reactive protein (p = 0.03) were associated with mortality in COVID-HIS. Both HScore and HLH-2004 criteria perform poorly for identifying COVID-HIS. Presence of bone marrow hemophagocytosis may help to identify about one-third of COVID-HIS missed by the Temple Criteria.

A simple protocol for determination of enantiopurity of amines using BINOL derivatives as chiral solvating agents via 1H- and 19F-NMR spectroscopic analysis.

A rapid and simple protocol for the determination of enantiopurity of primary and secondary amines was developed by using (S)-BINOL/(S)-BINOL derivatives/(R)-1,1'-binaphthyl-2,2'-diyl hydrogenphosphate as chiral solvating agents via 1H- and 19F-NMR spectroscopic analysis. In this protocol, the analyte and chiral solvating agent were directly mixed in an NMR tube in chloroform-d and after shaking for 30 seconds the 1H- and 19F-NMR spectra were recorded, which affords well-resolved resonance peaks for both the enantiomers present in an analyte. The enantiomeric excess of 1,2-diphenylethylenediamine was determined and linear relationship with coefficient of R 2 = 0.9995 was observed. The binding constant and associated ΔG values were also calculated for diastereomeric complexes formed between both the enantiomers of analyte 5 with CSA (S)-3a by using UV-visible spectroscopy.

Reed Sternberg-Like Cells in Non-Hodgkin Lymphoma: A Diagnostic Challenge.

Reed-Sternberg cells are distinguishing features of classical Hodgkin lymphoma. However, they are seen infrequently, in both B and T cells Non-Hodgkin lymphomas with a comparable morphology and immunophenotype. These cells are known as Reed-Sternberg-like cells. The characteristic background milieu of classical Hodgkin lymphoma is typically not present in Non-Hodgkin lymphomas, and Reed-Sternberg-like cells are typically present as dispersed cells or in tiny clusters. They are positive for CD30, show variable expression of B cell lineage markers and are negative for CD45/LCA in Non-Hodgkin lymphomas. Reed-Sternberg-like cells have phenotypes that are remarkably similar to those of conventional Reed-Sternberg cells. In this interesting case report, we discuss a case of disseminated B-cell Non-Hodgkin lymphoma with Reed-Sternberg-like cells that presented as a diagnostic challenge. It is essential to distinguish between classical Hodgkin lymphoma and Non-Hodgkin lymphomas due to distinct therapy protocols and prognosis. The presence of large CD30 positive Reed-Sternberg like cells may mimic Hodgkin's Lymphoma. However, monomorphic background population with CD20 positivity should always raise the suspicious of B-cell Non-Hodgkin lymphoma. Immunohistochemical detection of a panel of targets should always be applied to correctly diagnose these rare cases of B-cell Non-Hodgkin lymphoma with Reed-Sternberg like cells.

Placental Growth Factor in First Trimester of Pregnancy for Prediction of Maternal and Perinatal Adverse Outcomes.

Purpose of the study: Placental growth factor (PLGF) is an angiogenic factor in pregnancy. To find out correlation of plasma levels of placental growth factor in first trimester of pregnancy in Indian women who develop maternal and perinatal adverse outcomes was the aim of the study. Methods: A prospective longitudinal noninterventional study was done in the department of Obstetrics and Gynecology after obtaining ethics approval. After enrolling patients in the first trimester (11 weeks to 13 weeks 6 days), a questionnaire was filled for demographic characteristics. Uterine artery doppler was done for every patient and blood sample (5 ml) was taken by venu puncture of median cubital vein. Serum levels of PLGF were measured by enzyme linked immunosorbent assay using Thermo Scientific Pierce Human PLGF kit (Thermo Fisher Scientific, Inc., Waltham, MA, USA). Patients were followed for their whole antenatal period and delivery outcomes. Results: Incidence of preeclampsia in our study was 9.3% (15/161) and fetal growth restriction (FGR) was 19.8% (32/161). Neither BMI nor nulliparity was found to have statistically significant correlation with development of preeclampsia. However, history of preeclampsia was found to be significant risk factor for prediction of preeclampsia (p value < 0.04). Plasma levels of PLGF were significantly lower in preeclampsia and FGR group and this difference was statistically significant (p value < 0.04). 7.5% still born occurred in complicated group and 10% needed NNU/NICU admission in this group. Conclusion: Measuring PLGF levels in first trimester of pregnancy can help in prediction of preeclampsia and FGR.

Serum Tumor Necrosis Factor-Alpha Levels in Acute Leukemia and Its Prognostic Significance.

Introduction Tumor necrosis factor-alpha (TNF-α) is a pleiotropic cytokine that facilitates malignant cells in immune evasion, survival, and treatment resistance by generating a favorable milieu for them. It is shown to be ectopically produced by malignant/leukemic and immune cells in the tumor microenvironment, providing a tumor-supportive environment and playing an important part in the establishment and progression of malignant cells. It is linked to hyperleukocytosis, high blast count, and poor clinical outcomes in acute leukemia (AL). Considering the varied role and different expression patterns of tumor necrosis factor-alpha in acute leukemia and its clinical relevance, the present study was planned to monitor the level of tumor necrosis factor-alpha in patients with acute leukemia and its correlation with disease outcome. The aim of this study was to monitor the level of tumor necrosis factor-alpha in patients with acute leukemia at the time of diagnosis and after induction chemotherapy. Material and methods The study included cases classified as acute leukemia based on morphological examination, bone marrow analysis, and flow cytometry. In all patients with acute leukemia (n = 90) and controls (n = 10), the serum tumor necrosis factor-alpha level was measured using a Diaclone Human ELISA kit (Diaclone, Besancon, France) (solid phase sandwich ELISA) at diagnosis and after induction chemotherapy. Results Tumor necrosis factor-alpha levels were substantially higher in T-acute lymphoblastic leukemia (T-ALL) cases, followed by acute myeloid leukemia (AML) and B-acute lymphoblastic leukemia (B-ALL), at the time of diagnosis, compared to the control. A significant reduction in serum tumor necrosis factor-alpha level was seen in patients with acute leukemia after induction phase chemotherapy (P < 0.05). Tumor necrosis factor-alpha levels were considerably reduced (P < 0.001) in the majority of acute leukemia cases after the induction phase, while high tumor necrosis factor-alpha levels were positively correlated with incomplete remission status in the remaining cases. Conclusion Tumor necrosis factor-alpha is involved in the progression of acute leukemia and its relapse. High levels of tumor necrosis factor-alpha are linked to leukocytosis, high blast counts, and worse survival in patients with acute leukemia. Monitoring of tumor necrosis factor-alpha may be helpful in patients with acute leukemia in view of available antitumor necrosis factor-alpha therapy.