Shades of Blue: A Case Series of Acquired Methemoglobinemia.

Acquired methemoglobinemia (MetHb) is a rare but potentially life-threatening condition that has varied etiology, usually toxin- or drug-induced. We had five cases of acquired methemoglobinemia during six months. Their presentation varied from an asymptomatic state to respiratory distress. The presence of cyanosis and low oxygen saturation (SpO2), despite normal partial pressure of oxygen (PaO2) and chocolate brown-colored blood, were diagnostic clues present in all cases. A high level of methemoglobinemia was detected on arterial blood gas (ABG), confirming the diagnosis. Methylene blue was used as an antidote along with supportive care in symptomatic cases. All these cases of methemoglobinemia recovered completely. A high index of suspicion for methemoglobinemia should be maintained in cases presenting with persistent hypoxia or cyanosis despite normal PaO2.

Uncovering the Unusual: A Case of Mixed Connective Tissue Disease With Rare Presentation, Atypical Complications, and Therapeutic Dilemmas.

Mixed connective tissue disease (MCTD) is an overlap syndrome characterized by features of systemic lupus erythematosus, scleroderma, and polymyositis, along with the presence of the U1RNP antibody. A 46-year-old female patient presented with severe anemia, cough, and breathlessness, and was diagnosed with cold agglutinin disease, a type of autoimmune hemolytic anemia (AIHA). Autoimmune workup revealed MCTD by positive antinuclear and U1RNP antibodies. She had bilateral miliary mottling on X-ray and a tree-in-bud appearance on high-resolution computed tomography of the thorax, which were suggestive of pulmonary tuberculosis. Standard therapy with steroids was not advisable. She was subsequently started on anti-tuberculosis treatment (anti-Koch's therapy), followed by steroid therapy and immunosuppressive therapy after three weeks. The patient responded well to treatment, but after two months, she developed cytomegalovirus (CMV) retinitis. Adult-onset CMV disease may occur as a result of primary infection, reinfection, or activation of a latent infection. Although not directly related, it can occur as an atypical association in the setting of immunosuppressive therapy. Morbidity and mortality are significantly increased in this population secondary to infectious potentiation: immunosuppression causes infections, and infections cause AIHA. The management of MCTD and secondary AIHA and immunosuppression poses a therapeutic challenge.

Effect of Ramipril on Cardiac Autonomic Neuropathy in Patients With Type II Diabetes Mellitus.

Background Cardiovascular autonomic neuropathy (CAN), an important form of DAN is caused by the impairment of the autonomic nerve fibers that innervate the heart and blood vessels and leads to abnormalities in cardiovascular dynamics. The earliest finding of CAN, even at the subclinical stage, is a decrease in heart rate variability (HRV). Objective The objective is to assess the effect of ramipril 2.5mg once daily on cardiac autonomic neuropathy in type II DM patients as an add-on to a standard antidiabetic regimen for a duration of 12 months. Materials and methods A prospective, open-label, randomized, parallel-group study was conducted on type II DM with autonomic dysfunction. Patients in Group A received tablet ramipril 2.5mg daily along with the standard antidiabetic regimen which consist of Tab Metformin 500mg twice a day and Tab Vildagliptin 50mg twice a day and group B received only the standard antidiabetic regimen for 12 months. Results Among 26 patients with CAN, 18 patients completed the study. After one year in group A, Delta HR value increases from 9.77±1.71 to 21.44±8.44 and the E:I ratio (ratio of the longest R-R interval during expiration and shortest R-R interval during inspiration) improved from 1.23±0.35 to 1.29±0.23 signifying significant improvement in parasympathetic tone. Results of the postural test showed significant improvement in SBP. Analysis of HRV by time domain method showed that the standard deviation of RR (SDRR) interval and Standard deviation of differences between adjacent RR interval (SDSD) value increased significantly in group A. Analysis of HRV frequency domain indices showed that LFP:HFP ratio improved after treatment in ramipril group indicating improvement in sympatho-vagal balance. Conclusion Ramipril improves parasympathetic component more as compared to sympathetic component of DCAN in type II DM. Ramipril could be a promising option having favorable long-term outcomes in diabetic patients especially when treatment begins at subclinical stage.

Predictors of Mortality among Patients Hospitalized with COVID-19 during the First Wave in India: A Multisite Case-Control Study.

Severe acute respiratory syndrome coronavirus 2 disease (COVID-19) has caused more than 6 million deaths globally. Understanding predictors of mortality will help in prioritizing patient care and preventive approaches. This was a multicentric, unmatched, hospital-based case-control study conducted in nine teaching hospitals in India. Cases were microbiologically confirmed COVID-19 patients who died in the hospital during the period of study and controls were microbiologically confirmed COVID-19 patients who were discharged from the same hospital after recovery. Cases were recruited sequentially from March 2020 until December-March 2021. All information regarding cases and controls was extracted retrospectively from the medical records of patients by trained physicians. Univariable and multivariable logistic regression was done to assess the association between various predictor variables and deaths due to COVID-19. A total of 2,431 patients (1,137 cases and 1,294 controls) were included in the study. The mean age of patients was 52.8 years (SD: 16.5 years), and 32.1% were females. Breathlessness was the most common symptom at the time of admission (53.2%). Increasing age (adjusted odds ratio [aOR]: 46-59 years, 3.4 [95% CI: 1.5-7.7]; 60-74 years, 4.1 [95% CI: 1.7-9.5]; and ≥ 75 years, 11.0 [95% CI: 4.0-30.6]); preexisting diabetes mellitus (aOR: 1.9 [95% CI: 1.2-2.9]); malignancy (aOR: 3.1 [95% CI: 1.3-7.8]); pulmonary tuberculosis (aOR: 3.3 [95% CI: 1.2-8.8]); breathlessness at the time of admission (aOR: 2.2 [95% CI: 1.4-3.5]); high quick Sequential Organ Failure Assessment score at the time of admission (aOR: 5.6 [95% CI: 2.7-11.4]); and oxygen saturation < 94% at the time of admission (aOR: 2.5 [95% CI: 1.6-3.9]) were associated with mortality due to COVID-19. These results can be used to prioritize patients who are at increased risk of death and to rationalize therapy to reduce mortality due to COVID-19.

An Assessment of the Utility of Serum Fructosamine in the Diagnosis and Monitoring of Diabetes Mellitus.

BACKGROUND: Fructosamine (FA) has gained importance as a new biomarker for hyperglycemia in the past decade and may be of indispensable use in certain conditions where hemoglobin A1c (HbA1c) falls short of utility such as disorders of red blood cells, patients with rapid glycemic excursions requiring more short-term monitoring, pregnancy, chronic kidney disease, etc. Methods: The present study was a hospital-based observational cross-sectional study conducted in the Department of Biochemistry, All India Institute of Medical Sciences (AIIMS), Nagpur, India. Serum HbA1c, FA, albumin-corrected fructosamine (AlbF), total protein-corrected FA (PrF), hemoglobin (Hb), and hematocrit (Hct) were estimated in 32 controls (Group I) and 32 cases of diabetes mellitus (DM) (Group II). The clinical data and lab results were presented as mean±SD/±standard error (SE) of the mean. Student's t-test and ANOVA were used to compare various parameters between the groups. Pearson correlation analysis was performed to assess the correlation between different diagnostic parameters. The receiver operating characteristic (ROC) curve was plotted to assess the diagnostic significance and cut-off value for FA, AlbF, and PrF. RESULTS: The controls and cases were matched for age and gender distribution. Serum HbA1c (p<0.0001), serum FA (p<0.0001), fasting blood sugar (p=0.001), postprandial blood sugar (p<0.0001), random blood sugar (p=0.001), hematocrit (p=0.002), AlbF (p<0.0001), and PrF (p<0.0001) were found to be significantly higher in known diabetic subjects compared to controls. The case group was further subdivided into pre-diabetic and diabetic groups. On correlation analysis of HbA1c with various parameters, a moderate correlation of HbA1c was noted with FA (r=0.522, p<0.0001) and AlbF (r=0.375, p=0.002) in all subjects. Additionally, a moderate correlation of FA (r=0.479, p=0.033), AlbF (r=0.444, p=0.050), and PrF (r=0.441, p=0.065) with HbA1c was also found in subjects with diabetic range glycemia. No such correlation was noted in the pre-diabetic group. No significant correlation was noted between FA and its corrected values in any range of glycemia. None of the parameters assessing glycemia were found to be significantly affected by hemoglobin status. On ROC curve analysis, HbA1c was found to be the best parameter (area under the curve (AUC) =83%, p<0.0001) followed by AlbF (AUC= 80.5%, p<0.0001) and uncorrected FA (AUC=80.5%, p<0.0001) to diagnose DM. CONCLUSION: Serum FA should be considered a valid diagnostic biomarker and of indispensable use in special populations where HbA1c falls short of utility such as patients with red blood cell disorders or those showing rapid glycemic excursions such as those on corticosteroid therapy or insulin therapy, etc. It exhibits additional advantages over HbA1c with respect to lower reagent cost and easy automation on any conventional laboratory instruments based on simple colorimetry.

Association of vitamin D with the severity of disease and mortality in COVID-19: Prospective study in central India.

Background: Many factors have been proposed to be associated with the severity of disease and mortality in COVID-19. Vitamin D had recently been reviewed as one of these factors. Aim and Objectives: To evaluate the association between Vitamin D and the disease severity and mortality in COVID-19. Materials and Methods: After approval from Institutional Ethics Committee, this prospective cohort study was carried out in selected tertiary care teaching medical institutes of Central India. Participants were COVID-19 patients of the age group of 18 years and above admitted during the study period. They were categorized into four groups as asymptomatic (Group A), mild (Group B), moderate (Group C), and severe (Group D) based on clinical symptoms, respiratory rate, oxygen saturation, and chest imaging. Serum level of Vitamin 25(OH) D was measured using chemiluminescent immunoassay. The outcome of the disease was classified as recovery and death during hospitalization. The association of sociodemographic and medical characteristics with treatment outcome was studied using an appropriate statistical test. A full logistic regression model was built for the assessment of the relationship between treatment outcomes with Vitamin D level. Further, one receiver operating characteristic curve was developed to examine the prognostic significance of Vitamin D levels in COVID-19 patients. Results: Out of 748 enrolled patients, 44 (5.88%), had severe disease (Group D). A total of 721 cases (96.39%) recovered and were discharged, whereas 27 (3.61%) died during hospitalization. Mean Vitamin D level was found to be significantly different in discharged patients compared to those who were deceased. Increasing age-adjusted odds ratio (AOR) (95% confidence interval [CI]=1.07 [1.02-1.12]), known hypertension AOR (95%CI) = 3.38 (1.13-10.08), and diabetes mellitus AOR (95%CI) =28.5 (6.04-134.13) were found to be significant predictors of death among COVID-19 patients. Increasing Vitamin D level was found to be protective against COVID-19-related death (AOR (95% CI = 0.87 [0.80-0.94]). Conclusion: Vitamin D was significantly associated with the disease severity and mortality in COVID-19.

Résumé Contexte: Il a été proposé que de nombreux facteurs soient associés à la gravité de la maladie et de la mortalité dans le Covid - 19. La vitamine D avait récemment été examinée comme l'un de ces facteurs. Objectif et objectifs: évaluer l'association entre la vitamine D et la gravité de la maladie et la mortalité dans le Covid-19. Matériel et méthodes: Après l'approbation du comité d'éthique institutionnel, cette étude de cohorte prospective a été réalisée dans des instituts médicaux d'enseignement des soins tertiaires de l'Inde centrale. Les participants étaient des patients Covid-19 du groupe d'âge de 18 ans et plus admis au cours de la période d'étude. Ils ont été classés en quatre groupes comme asymptomatiques (groupe A), légers (groupe B), modérés (groupe C) et sévères (groupe D) sur la base des symptômes cliniques, de la fréquence respiratoire, de la saturation en oxygène et de l'imagerie thoracique. Niveau sérique de la vitamine 25 (OH) DWAS mesuré en utilisant l'immunodosage chimioluminescent. L'issue de la maladie a été classée comme récupération et décès pendant l'hospitalisation. L'association des caractéristiques sociodémographiques et médicales avec les résultats du traitement a été étudiée à l'aide d'un test statistique approprié. Un modèle de régression logistique complet a été construit pour l'évaluation de la relation entre les résultats du traitement au niveau de la vitamine D. De plus, une courbe caractéristique de fonctionnement du récepteur a été développée pour examiner la signification pronostique des niveaux de vitamine D chez les patients COVID-19. Résultats: Sur 748 patients inscrits, 44 (5,88%), avaient une maladie grave (groupe D). Un total de 721 cas (96,39%) ont récupéré et ont été libérés, tandis que 27 (3,61%) sont décédés pendant l'hospitalisation. Le niveau moyen de la vitamine D s'est révélé significativement différent chez les patients libérés par rapport à ceux qui ont été décédés. Augmentation du rapport de cotes ajusté à l'âge (AOR) (intervalle de confiance à 95% [IC] = 1,07 [1,02­1,12]), hypertension connue AOR (IC à 95%) = 3,38 (1,13­10,08) et diabète mellite aor (IC 95% ) = 28,5 (6,04­134.13) se sont révélés être des prédicteurs significatifs de la mort chez les patients COVID-19. L'augmentation du niveau de vitamine D s'est avérée protectrice contre la mort liée au Covid - 19 (AOR (IC à 95% = 0,87 [0,80­0,94]). Conclusion: La vitamine D était significativement associée à la gravité de la maladie et à la mortalité dans le Covid - 19. Mots clés: Covid - 19, tempête de cytokines, mortalité, gravité, vitamine D.

Association of COVID-19 Real-Time Reverse Transcription-Polymerase Chain Reaction (RT-PCR) Cycle Threshold Value With Surrogate Markers of Disease Severity.

Introduction The cycle threshold (Ct) value in real-time reverse transcription-polymerase chain reaction (RT-PCR) serves as a criterion to diagnose coronavirus disease 2019 (COVID-19) and is inversely proportional to viral load. Levels of inflammatory markers such as aspartate aminotransferase (AST), ferritin, D-dimer, high sensitivity C-reactive protein (hs-CRP), and lactate dehydrogenase (LDH) are used as quantitative measures of COVID-19 severity. We examined the association between these markers and Ct values. Methodology This retrospective data analysis included 400 patients with positive RT-PCR results for COVID-19 who were admitted to a tertiary care hospital. Clinical and biochemical data were accessed from the hospital information management system. Associations of clinical parameters and markers of disease severity (e.g., polymorph, AST, hs-CRP, D-dimer, LDH, and ferritin levels) with Ct values were assessed. Observations LDH, ferritin, D-dimer, and hs-CRP were found to be significantly higher in moderate and severe groups than in the mild COVID-19 group. AST, ferritin, and hs-CRP levels were also significantly higher in severe COVID-19 subjects, compared to moderate COVID-19 subjects. Ct values for the E (envelop) gene and ORF (open reading frame) 1b gene were found to be significantly higher in those with severe COVID-19. Polymorph counts in subjects with Ct values of 25 or higher were significantly increased, compared to those with Ct values under 30. LDH, D-dimer, and hs-CRP levels in subjects with Ct values over 30 were significantly lower than for those with Ct values under 30. Ferritin was the best independent predictor of non-survival in study subjects, with an area under the curve (AUC) of 85.5% (95% confidence interval = 73.2-95.9). The Ct value for the E gene had an AUC of 75.1%, and the ORF1b gene had an AUC of 64.5%. However, no significant correlation was detected between any parameter and Ct value. Conclusion Polymorph, LDH, ferritin, D-dimer, and hs-CRP levels were significantly elevated in subjects with low E gene Ct values. Also, these subjects were at risk of severe disease and fatality. Ct values for the E gene thus could serve as an early indicator for patients at risk of severe disease and death.

Neutrophil-to-Lymphocyte Ratio as a Predictor of Disease Severity and Mortality in Coronavirus Disease 2019: Prospective Study From Central India.

BACKGROUND: Clinical presentation of coronavirus disease 2019 (COVID-19) varies from an asymptomatic state to severe disease characterized by acute respiratory distress syndrome, respiratory failure, thrombosis, and multi-organ dysfunction syndrome. The neutrophil-to-lymphocyte ratio (NLR) has been reviewed as one of the laboratory factors that have been proposed to predict the severity of disease and mortality in COVID-19 pandemic. AIM AND OBJECTIVES: To evaluate the association between NLR and the disease severity and mortality in COVID-19. MATERIALS AND METHODS: After approval from Institutional Ethics Committee, this prospective cohort study was carried out in a tertiary-care teaching medical institute of Central India. COVID-19 patients of the age group 18 years and above admitted during the study period were included. Cases were categorized into four groups as asymptomatic (Group A), mild (Group B), moderate (Group C), and severe (Group D) based on clinical symptoms, respiratory rate, oxygen saturation, and chest imaging. NLR was calculated by doing a complete blood count at the time of hospitalization by the Mindray BC-6000 auto hematology analyzer. The outcome of the disease was classified as recovery and death during hospitalization. Receiver operating characteristic (ROC) curve analysis was used to assess the ability of NLR at admission to predict severe COVID-19 or mortality. Ordinal regression analysis was used to assess the impact of NLR on disease severity and mortality. RESULTS: Mean NLR was significantly higher in the severe COVID-19 group as compared to the mild/moderate group and in deceased as compared to discharged cases. ROC curve analysis revealed NLR to be an excellent predictor of disease severity as well as a prognostic parameter for risk of death. NLR was found to be a significant independent positive predictor for contracting the severe disease (Odd's ratio 1.396, 95% CI=1.112-1.753, p=0.004) and mortality (Odd's ratio 1.276, 95% CI=1.085-1.499, p=0.003). CONCLUSION: High NLR was significantly associated with the disease severity and mortality in COVID-19.

The study of serum hsCRP, ferritin, IL-6 and plasma D-dimer in COVID-19: a retrospective study.

OBJECTIVES: The cut off values for serum high sensitivity C-reactive protein (hsCRP), ferritin, interleukin 6 (IL-6) and plasma D-dimer could be of profound help in detecting COVID-19 patients at risk of adverse outcomes. Therefore, the aim of the present study is to determine the cut off values of the serum hsCRP, ferritin, IL-6 and plasma D-dimer in predicting mortality in COVID-19 patients. METHODS: Four hundred RT-PCR confirmed cases of COVID-19 were sub divided into two groups based on their outcome during hospitalisation. Group I consisted of survivors and Group II consisted of non-survivors. The survivors were further divided into three sub-groups: mild, moderate and severe based on the severity of infection. The laboratory data of serum hsCRP, ferritin, IL-6 and plasma D-dimer for all these patients was retrieved from the Medical Record Section of the Hospital. RESULTS: Mean serum hsCRP, ferritin, IL-6 and plasma D-dimer levels were significantly higher in non-survivors as compared to survivors of COVID-19. The levels of these biomarkers correlated with the severity of COVID-19 illness. ROC curve analysis revealed that plasma D-dimer is having a better predictive value as compared to other parameters in predicting mortality in COVID-19. CONCLUSIONS: The serum hsCRP, ferritin, IL-6 and plasma D-dimer levels could be used in risk stratification of COVID-19 patients. The optimum cut off given by the current study could be considered in predicting adverse outcome in these patients. Amongst the many studied biomarkers, plasma D-dimer might be the best early biomarker to predict mortality in COVID-19 patients.

Symptomatology and Relationship Between Symptoms and Duration Among COVID-19 Patients in a COVID-19 Care Hospital in Central India.

The COVID-19 pandemic has affected the world population across the globe. India has the second largest number of cases and the third largest number of deaths due to COVID-19 in the world. There have been close to 4.4 lakh deaths due to COVID-19 in India alone. The second wave in India has led to devastating consequences, particularly among the young population. The initial clinical symptoms of COVID-19 are similar to all types of viral pneumonia, with varying degrees of severity. The cases' clinical manifestations include fever, nonproductive cough, dyspnea, myalgia, and fatigue. This study was undertaken with the purpose of identifying the relationship between the symptoms and duration in COVID-19-affected patients. The common presenting symptoms were fever (44.5%), sore throat (38.7%), and cough (36.12%). Most of the cases presented with a combination of fever with cough (35%) and fever with sore throat (33%). The duration of symptoms varied from one to 17 days with a mean of 5.75 days. Despite vaccination being started, the risk of the imminent third wave in the country is existential. Mutations in the coronavirus pose a threat to the vulnerable population. It is important to identify the combination of symptoms most predictive of COVID-19 to help guide recommendations for self-isolation, testing, and preventing further spread of the disease. Further studies using these models can yield better results in surveillance and containing this infectious disease.