Study of Glycemic Variability in Well-controlled Type 2 Diabetic Patients Using Continuous Glucose Monitoring System.

INTRODUCTION: The world has changed tremendously for patients suffering from diabetes mellitus with the development of cutting-edge technologies like continuous glucose monitoring and flash glucose monitoring systems. Now, the details of constant fluctuations of glucose in their blood can be monitored not only by medical professionals but also by patients, and this is called glycemic variability (GV). Traditional metrics of glycemic control measurement, such as glycated hemoglobin (HbA1c), fail to reflect various short-term glycemic changes like postprandial hyperglycemia and hypoglycemic episodes, paving the way to the occurrence of various diabetic complications even in asymptomatic, well-controlled diabetic patients. This need for advanced management of diabetes and effective monitoring of these swings in blood glucose can be met by using a continuous glucose monitoring system (CGMS). AIM AND OBJECTIVE: To evaluate the extent of GV in well-controlled type 2 diabetes mellitus (T2DM) patients using a flash CGMS and to assess the correlation between GV and HbA1c. MATERIALS AND METHODS: A hospital-based prospective observational study was carried out from May 2020 to Oct 2021 at the Department of Medicine, SMS Hospital, Jaipur, Rajasthan (India), after approval from the Ethics Committee of the institution. A total of 30 patients with well-controlled T2DM (HbA1c was ≥6.5, but ≤7.5) were included in the study using simple random techniques after written informed consent from patients. Patients were studied for glycemic excursions over a period of 7 days by using FreeStyle® Libre Pro™, which is a flash glucose monitoring system. The CGM sensor was attached to the left upper arm of the patient on day 0 and removed on day 7. The data recorded in the sensor was then retrieved using pre-installed computer software and analyzed using standard CGM metrics like standard deviation (SD), percentage coefficient of variation (%CV), time above range (TAR), time below range (TBR), and time in range (TIR), out of which %CV was used to quantify GV. %CV has been used to cluster patients into four cohorts from best to worst, namely: best/low CV ≤ 10%, intermediate CV from 10 to 20%, high CV from 20 to 30%, and very high CV of >30%. Scatterplots are used to establish correlations between various parameters. RESULT: Data from a total of 30 patients were analyzed using CGMS and thus used for calculating standard CGM metrics; glucose readings every 15 minutes were recorded consecutively for 7-day periods, making it a total of 672 readings for each patient. Interpreting the CGM data of all 30 patients, the following results were found: the mean blood glucose of all cases is 134.925 ± 22.323 mg/dL, the mean SD of blood glucose of all cases is 35.348 ± 9.388 mg/dL, the mean of %CV of all cases is 26.376 ± 6.193%. CGM parameters of time are used in the form of percentages, and the following results were found: the mean of TAR, TBR, and TIR is 14.425 ± 13.211, 5.771 ± 6.808, and 82.594 ± 12.888%, respectively. Clustering the patients into cohorts, the proportion of patients exhibiting best/low %CV (10%) is 0, intermediate %CV (10-20%) is 16.67% (five out of 30 patients), high %CV (20-30%) is 50% (15 out of 30 patients) and very high %CV (>30%) is 33.33% (10 out of 30 patients). Also, there is no significant correlation found between HbA1c and %CV (ρ = 0.076, p-value = 0.690); a significant negative correlation was found between %CV and TIR (ρ = -0.604, p < 0.001S); a positive correlation of %CV with TAR and TBR is significant (ρ = 0.816, p-value of <0.001). CONCLUSION: Using a flash CGMS device and considering %CV as the parameter and primary measure of GV, the study demonstrated the overall instability of a person's glycemic control, making note of unrecognized events of hypoglycemia and hyperglycemia in asymptomatic well-controlled T2DM patients, revealing the overall volatile glycemic control. The most important finding of this study is that even those diabetics who are considered well-controlled experience a great degree of GV as assessed by CGM-derived metrics. This study also demonstrated that there is no significant correlation between HbA1c and GV, suggesting that patients may not have optimal control of their diabetes despite having "normal HbA1c" values; hence, GV can be considered an HbA1c-independent danger factor, having more harmful effects than sustained hyperglycemia in the growth of diabetic complications. So, by using CGM-derived metrics, the measurement of GV has the potential to complement HbA1c data. In this manner, a more comprehensive assessment of glycemic excursions can be provided for better treatment decisions, thereby facilitating optimal glycemic control, which is essential for reducing overall complications and promoting good quality of life.

A Study of Relationships between the HbA1c Level and Inflammatory Markers, Neutrophil-to-Lymphocyte Ratio, and Monocyte-to-Lymphocyte Ratio in Controlled and Uncontrolled Type 2 Diabetes Mellitus.

AIM AND OBJECTIVE: To assess the relationship between glycated hemoglobin (HbA1c) with inflammatory markers, neutrophil-to-lymphocytes ratio (NLR), and monocyte-to-lymphocytes ratio (MLR) in controlled and uncontrolled type 2 diabetes patients. MATERIALS AND METHODS: This was a hospital-based cross-sectional study conducted at the Department of Medicine, SMS Hospital, and an attached group of hospitals (Jaipur, Rajasthan, India) after informed consent from the Ethics Committee of the institute. After obtaining informed consent from patients who met the inclusion and exclusion criteria, 200 diabetic patients were included in the study using the simple randomization method. Following a detailed history and diagnosis, vital demographic information, and blood tests were collected from patients via a predesigned preliminary questionnaire. The following blood tests were collected: white blood cell (WBC), Hb, hematocrit (HCT), red cell distribution width (RDW), neutrophils, lymphocytes, HbA1c, blood glucose, NLR ratio, and MLR ratio. Data were entered and analyzed using Statistical Package for the Social Sciences version 22. RESULTS: The mean age of patients with controlled diabetes mellitus was 54.10 years, while that of patients with uncontrolled diabetes mellitus was 55.3 years. Glycemic control was more in the age group of 51-60 years. Around 54% of males and 46% of females were included in the present study, and no association was found between the two genders with poor and good glycemic control. Around 63.29% of participants with uncontrolled diabetes have an increased NLR, and 61.39% of participants with uncontrolled diabetes have an increased MLR. A strong association was found between the NLR and MLR with the glycemic control. CONCLUSION: Uncontrolled diabetes mellitus had a positive association with inflammatory markers, that is, NLR and MLR. STATEMENT OF SIGNIFICANCE: Diabetes mellitus is the most common metabolic disorder in Asian countries. It leads to many acute and chronic complications in uncontrolled diabetes. Markers like the NLR ratio and MLR ratio are inexpensive and easily available for blood investigation. Hence, these markers are quite useful in differentiating controlled and uncontrolled diabetes and, therefore, useful in predicting blood sugar control in type 2 diabetes mellitus.

Prevalence of co-existent COVID-19-associated pulmonary aspergillosis (CAPA) and its impact on early mortality in patients with COVID-19-associated pulmonary mucormycosis (CAPM).

BACKGROUND: Data on mixed mould infection with COVID-19-associated pulmonary aspergillosis (CAPA) and COVID-19-associated pulmonary mucormycosis (CAPM) are sparse. OBJECTIVES: To ascertain the prevalence of co-existent CAPA in CAPM (mixed mould infection) and whether mixed mould infection is associated with early mortality (≤7 days of diagnosis). METHODS: We retrospectively analysed the data collected from 25 centres across India on COVID-19-associated mucormycosis. We included only CAPM and excluded subjects with disseminated or rhino-orbital mucormycosis. We defined co-existent CAPA if a respiratory specimen showed septate hyphae on smear, histopathology or culture grew Aspergillus spp. We also compare the demography, predisposing factors, severity of COVID-19, and management of CAPM patients with and without CAPA. Using a case-control design, we assess whether mixed mould infection (primary exposure) were associated with early mortality in CAPM. RESULTS: We included 105 patients with CAPM. The prevalence of mixed mould infection was 20% (21/105). Patients with mixed mould infection experienced early mortality (9/21 [42.9%] vs. 15/84 [17.9%]; p = 0.02) and poorer survival at 6 weeks (7/21 [33.3] vs. 46/77 [59.7%]; p = 0.03) than CAPM alone. On imaging, consolidation was more commonly encountered with mixed mould infections than CAPM. Co-existent CAPA (odds ratio [95% confidence interval], 19.1 [2.62-139.1]) was independently associated with early mortality in CAPM after adjusting for hypoxemia during COVID-19 and other factors. CONCLUSION: Coinfection of CAPA and CAPM was not uncommon in our CAPM patients and portends a worse prognosis. Prospective studies from different countries are required to know the impact of mixed mould infection.

Revised ISHAM-ABPA working group clinical practice guidelines for diagnosing, classifying and treating allergic bronchopulmonary aspergillosis/mycoses.

BACKGROUND: The International Society for Human and Animal Mycology (ISHAM) working group proposed recommendations for managing allergic bronchopulmonary aspergillosis (ABPA) a decade ago. There is a need to update these recommendations due to advances in diagnostics and therapeutics. METHODS: An international expert group was convened to develop guidelines for managing ABPA (caused by Aspergillus spp.) and allergic bronchopulmonary mycosis (ABPM; caused by fungi other than Aspergillus spp.) in adults and children using a modified Delphi method (two online rounds and one in-person meeting). We defined consensus as ≥70% agreement or disagreement. The terms "recommend" and "suggest" are used when the consensus was ≥70% and <70%, respectively. RESULTS: We recommend screening for A. fumigatus sensitisation using fungus-specific IgE in all newly diagnosed asthmatic adults at tertiary care but only difficult-to-treat asthmatic children. We recommend diagnosing ABPA in those with predisposing conditions or compatible clinico-radiological presentation, with a mandatory demonstration of fungal sensitisation and serum total IgE ≥500 IU·mL-1 and two of the following: fungal-specific IgG, peripheral blood eosinophilia or suggestive imaging. ABPM is considered in those with an ABPA-like presentation but normal A. fumigatus-IgE. Additionally, diagnosing ABPM requires repeated growth of the causative fungus from sputum. We do not routinely recommend treating asymptomatic ABPA patients. We recommend oral prednisolone or itraconazole monotherapy for treating acute ABPA (newly diagnosed or exacerbation), with prednisolone and itraconazole combination only for treating recurrent ABPA exacerbations. We have devised an objective multidimensional criterion to assess treatment response. CONCLUSION: We have framed consensus guidelines for diagnosing, classifying and treating ABPA/M for patient care and research.

Risk factors, mortality, and predictors of survival in COVID-19-associated pulmonary mucormycosis: a multicentre retrospective study from India.

OBJECTIVES: To compare COVID-19-associated pulmonary mucormycosis (CAPM) with COVID-19-associated rhino-orbital mucormycosis (CAROM), ascertain factors associated with CAPM among patients with COVID-19, and identify factors associated with 12-week mortality in CAPM. METHODS: We performed a retrospective multicentre cohort study. All study participants had COVID-19. We enrolled CAPM, CAROM, and COVID-19 subjects without mucormycosis (controls; age-matched). We collected information on demography, predisposing factors, and details of COVID-19 illness. Univariable analysis was used to compare CAPM and CAROM. We used multivariable logistic regression to evaluate factors associated with CAPM (with hypoxemia during COVID-19 as the primary exposure) and at 12-week mortality. RESULTS: We included 1724 cases (CAPM [n = 122], CAROM [n = 1602]) and 3911 controls. Male sex, renal transplantation, multimorbidity, neutrophil-lymphocyte ratio, intensive care admission, and cumulative glucocorticoid dose for COVID-19 were significantly higher in CAPM than in CAROM. On multivariable analysis, COVID-19-related hypoxemia (aOR, 2.384; 95% CI, 1.209-4.700), male sex, rural residence, diabetes mellitus, serum C-reactive protein, glucocorticoid, and zinc use during COVID-19 were independently associated with CAPM. CAPM reported a higher 12-week mortality than CAROM (56 of the 107 [52.3%] vs. 413 of the 1356 [30.5%]; p = 0.0001). Hypoxemia during COVID-19 (aOR [95% CI], 3.70 [1.34-10.25]) and Aspergillus co-infection (aOR [95% CI], 5.40 [1.23-23.64]) were independently associated with mortality in CAPM, whereas surgery was associated with better survival. DISCUSSION: CAPM is a distinct entity with a higher mortality than CAROM. Hypoxemia during COVID-19 illness is associated with CAPM. COVID-19 hypoxemia and Aspergillus co-infection were associated with higher mortality in CAPM.

Impact of HRCT pattern on six-minute walk test in patients with interstitial lung disease-An observational study.

Background: Forced vital capacity (FVC) and six-minute walk distance (6MWD) are robust markers in interstitial lung diseases (ILD) to assess severity and prognosis. It is unknown whether high-resolution computed tomography pattern has any independent effect on the exercise capacity in ILD. We compared six-minute walk test (6MWT) parameters between usual interstitial pneumonia (UIP) and non-UIP ILD after adjusting for FVC. Methods: Data from a tertiary care ILD clinic were retrospectively analysed. Based on HRCT, patients were classified as UIP and non-UIP. 6MWT parameters and FVC were recorded for enrolled patients. 6MWD, distance-saturation product (DSP) and exertional desaturation were compared between UIP and non-UIP, using analysis of covariance (ANCOVA), with per cent predicted FVC as covariate. Patients were grouped as mild (≥70%), moderate (51%-69%) and severe (≤50%) based on FVC severity. Results: Out of 169 patients enrolled, only patients with all three data points: spirometry, 6MWT and HRCT were included in the analysis (n = 139). UIP group comprised 56 (40.3%), while non-UIP group had 83 (59.7%) patients. More females and lesser smokers were present in non-UIP group. Mean predicted FVC% was similar between the two HRCT groups (P = 0.611) and had a statistically significant, though very weak to weak correlation with 6MWT parameters {6MWD (r = 0.138); pred 6MWD% (r = 0.170); desaturation (r = -0.227); DSP index (r = 0.166)}. Analysis of covariance showed no statistically significant difference in the 6MWT parameters between UIP and non-UIP groups for similar FVC levels. Conclusion: For a similar level of lung function, exercise capacity was similar for patients with UIP and non-UIP pattern ILD.

Utility and timing of the respiratory rate-oxygenation index in the prediction of high-flow oxygen therapy failure in acute hypoxemic respiratory failure of infective etiology: a prospective observational study.

During and following the COVID-19 pandemic, the world has witnessed a surge in high-flow oxygen therapy (HFOT) use. The ability to provide high oxygenation levels with remarkable comfort levels has been the grounds for the same. Despite the advantages, delays in intubation leading to poor overall outcomes have been noticed in subgroups of patients on HFOT. The respiratory rate-oxygenation (ROX) index has been proposed to be a useful indicator to predict HFOT success. In this study, we have examined the utility of the ROX index prospectively in cases of acute hypoxemic respiratory failure (AHRF) due to infective etiologies. A total of 70 participants were screened, and 55 were recruited for the study. The majority of participants were males (56.4%), with diabetes mellitus being the most common comorbidity (29.1%). The mean age of the study subjects was 46.27±15.6 years. COVID-19 (70.9%) was the most common etiology for AHRF, followed by scrub typhus (21.8%). 19 (34.5%) experienced HFOT failure, and 9 (16.4%) subjects died during the study period. Demographic characteristics did not differ between either of the two groups (HFOT success versus failure and survived group versus expired group). The ROX index was significantly different between the HFOT success versus failure group at baseline, 2, 4, 6, 12, and 24 hours. The best cut-offs of the ROX index at baseline and 2 hours were 4.4 (sensitivity 91.7%, specificity 86.7%) and 4.3 (sensitivity 94.4% and specificity 86.7%), respectively. The ROX index was found to be an efficient tool in predicting HFOT failure in cases of AHRF with infective etiology.

To Estimate the Prevalence of Obesity and High Blood Pressure among Undergraduate Students at a University Medical Institution in North India.

Background: Hypertension is a major public health issue in India. Early detection and management of high blood pressure (BP) is crucial, especially among young adults. This study aimed to estimate the prevalence of obesity and hypertension among undergraduate medical students. Materials and methods: A cross-sectional study was conducted among 450 first year undergraduate medical students aged 18-25 years in S.M.S. Medical and Hospital Jaipur, Rajasthan after clearance from institutional ethics committee and written consent from participants. Anthropometric measurements like height, weight, BMI, waist circumference, hip circumference and blood pressure were recorded. Hypertension was defined as per JNC VIII guidelines. Data was analyzed using appropriate statistical tests. Results: Overall, 15.56% students were hypertensive and 40.67% were prehypertensive. Hypertension was more prevalent in males (18.83%) compared to females (12.33%) (p = 0.002). Overweight/obesity was present in 29.33% students, more common in males (37.67%) than females (21.15%) (p < 0.001). Obese students had higher rates of prehypertension (47%) and hypertension (28.8%). Abnormal waist-hip ratio and waist-stature ratio were significantly associated with hypertension (p < 0.001). Conclusion: Overweight/obesity and hypertension are highly prevalent among undergraduate medical students, especially males. Unhealthy lifestyles and risk factors need to be addressed to prevent long term morbidity. Routine screening and health promotion activities should be conducted for this high risk group. How to cite this article: Sharda K, Saxena P, Yadav SK, et al. To Estimate the Prevalence of Obesity and High Blood Pressure among Undergraduate Students at a University Medical Institution in North India. J Assoc Physicians India 2023;71(11):30-35.

Destabilizers of the thymidylate synthase homodimer accelerate its proteasomal degradation and inhibit cancer growth.

Drugs that target human thymidylate synthase (hTS), a dimeric enzyme, are widely used in anticancer therapy. However, treatment with classical substrate-site-directed TS inhibitors induces over-expression of this protein and development of drug resistance. We thus pursued an alternative strategy that led us to the discovery of TS-dimer destabilizers. These compounds bind at the monomer-monomer interface and shift the dimerization equilibrium of both the recombinant and the intracellular protein toward the inactive monomers. A structural, spectroscopic, and kinetic investigation has provided evidence and quantitative information on the effects of the interaction of these small molecules with hTS. Focusing on the best among them, E7, we have shown that it inhibits hTS in cancer cells and accelerates its proteasomal degradation, thus causing a decrease in the enzyme intracellular level. E7 also showed a superior anticancer profile to fluorouracil in a mouse model of human pancreatic and ovarian cancer. Thus, over sixty years after the discovery of the first TS prodrug inhibitor, fluorouracil, E7 breaks the link between TS inhibition and enhanced expression in response, providing a strategy to fight drug-resistant cancers.

A Delphi consensus statement for the management of post-COVID interstitial lung disease.

INTRODUCTION: As millions of people worldwide recover from COVID-19, a substantial proportion continue to have persistent symptoms, pulmonary function abnormalities, and radiological findings suggestive of post-COVID interstitial lung disease (ILD). To date, there is limited scientific evidence on the management of post-COVID ILD, necessitating a consensus-based approach. AREAS COVERED: A panel of experts in pulmonology and thoracic radiology was constituted. Key questions regarding the management of post-COVID ILD were identified. A search was performed on PubMed and EMBASE and updated till 1 March 2022. The relevant literature regarding the epidemiology, pathophysiology, diagnosis and treatment of post-COVID ILD was summarized. Subsequently, suggestions regarding the management of these patients were framed, and a consensus was obtained using the Delphi approach. Those suggestions which were approved by over 80% of the panelists were accepted. The final document was approved by all panel members. EXPERT OPINION: Dedicated facilities should be established for the care of patients with post-COVID ILD. Symptom screening, pulmonary function testing, and thoracic imaging have a role in the diagnosis. The pharmacologic and non-pharmacologic options for the management of post-COVID ILD are discussed. Further research into the pathophysiology and management of post-COVID ILD will improve our understanding of this condition.

Assessment of Six-Minute Walk Test Among Discharge-Ready Severe COVID-19 Patients: A Cross-Sectional Study.

Background Among patients hospitalized for severe pneumonia due to coronavirus disease (COVID-19), clinical stability and normal resting peripheral oxygen saturation (SpO2) levels are widely used as a discharge criterion after recovery. It is unknown whether a test to assess the functional exercise capacity, like a six-minute walk test (6MWT), can add to the appropriateness of discharge criteria. Methods A cross-sectional study was conducted at a tertiary care COVID-19 hospital in India from 01st to 31st May 2021. All patients considered fit for discharge after recovery from "severe" COVID-19 pneumonia were subjected to 6MWT. Fitness for discharge was assessed by clinical stability and resting SpO2 above 93% for three consecutive days. Patients were considered to have failed the 6MWT if there was ≥4% fall in SpO2 or if they could not complete the test. Serum samples were analyzed for levels of C-reactive protein (CRP), interleukin-6 (IL-6), and lactate dehydrogenase (LDH) at the time of discharge. Results Fifty-three discharge-ready patients with a mean age of 54.54 ± 14.35 years with a male preponderance (60.38%) were analyzed. Thirty-three (62.26%) patients failed the 6MWT with a median six-minute walk distance (6MWD) of 270 m (60-360). A total of 45 (84.91%) patients had a fall in SpO2 during the test. The median change in SpO2 (∆SpO2) was 5% ranging from -6% to 8%. Serum LDH was significantly higher among patients who failed the 6MWT with a median LDH of 334 IU/L (38.96-2339) versus 261 IU/L (49.2-494) (p = 0.02). The difference was not significant for CRP or IL-6. There was no statistically significant correlation between the inflammatory markers with either 6MWD or (∆SpO2). Conclusion Two-thirds of the patients considered fit for discharge after recovery from severe COVID-19 pneumonia failed 6MWT, implying reduced functional exercise capacity and exertional hypoxia. Serum LDH levels were higher in these patients but not in other inflammatory markers. None of the inflammatory markers at discharge correlated with 6MWD or ∆SpO2 of 6MWT.

Relationship of Computed Tomography Severity Score With Patient Characteristics and Survival in Hypoxemic COVID-19 Patients.

Background Computed tomography (CT) scans and CT severity scores (CTSS) are widely used to assess the severity and prognosis in coronavirus disease 2019 (COVID-19). CTSS has performed well as a predictor in differentiating severe from non-severe cases. However, it is not known if CTSS performs similarly in hospitalized severe cases with hypoxia at admission. Methods We conducted a retrospective comparative study at a COVID-care center from Western India between 25th April and 31st May 2021, enrolling all consecutive severe COVID-19 patients with hypoxemia (peripheral oxygen saturation < 94%). Neutrophil-lymphocyte ratio (NLR), C-reactive protein (CRP), interleukin-6 (IL-6), lactate dehydrogenase (LDH), D-dimer, ferritin, and CT thorax were done within 24h of admission before being initiated on any anti-COVID-19 therapy. CTSS was calculated by visual assessment and categorized into three severity categories and was correlated with laboratory markers and overall survival (OS). Statistical analysis was done using John's Macintosh Project (JMP) 15.0.0 ver. 3.0.0 (Cary, North Carolina). Results The median age of the study population (n-298) was 59 years (24-95) with a male preponderance (61.41%, n=183). The 15 and 30-day survivals were 67.64% and 59.90%, respectively. CTSS did not correlate with age, gender, time from vaccination, symptoms, or comorbidities but had a significant though weak correlation with LDH (p=0.009), D-dimer (p=0.006), and NLR (p=0.019). Comparing demographic and laboratory aspects using CT severity categories, only NLR (p=0.0146) and D-dimer (p=0.0006) had significant differences. The 15d-OS of mild, moderate, and severe CT categories were 88.62%, 70.39%, and 52.62%, respectively, while 30d-OS of three categories were 59.08%, 63.96%, and 49.12%, respectively. Conclusion Among hospitalized severe COVID-19 patients with hypoxemia at admission, CT severity categories correlate well with outcomes but not inflammatory markers at admission.

Definition, diagnosis, and management of COVID-19-associated pulmonary mucormycosis: Delphi consensus statement from the Fungal Infection Study Forum and Academy of Pulmonary Sciences, India.

COVID-19-associated pulmonary mucormycosis (CAPM) remains an underdiagnosed entity. Using a modified Delphi method, we have formulated a consensus statement for the diagnosis and management of CAPM. We selected 26 experts from various disciplines who are involved in managing CAPM. Three rounds of the Delphi process were held to reach consensus (≥70% agreement or disagreement) or dissensus. A consensus was achieved for 84 of the 89 statements. Pulmonary mucormycosis occurring within 3 months of COVID-19 diagnosis was labelled CAPM and classified further as proven, probable, and possible. We recommend flexible bronchoscopy to enable early diagnosis. The experts proposed definitions to categorise dual infections with aspergillosis and mucormycosis in patients with COVID-19. We recommend liposomal amphotericin B (5 mg/kg per day) and early surgery as central to the management of mucormycosis in patients with COVID-19. We recommend response assessment at 4-6 weeks using clinical and imaging parameters. Posaconazole or isavuconazole was recommended as maintenance therapy following initial response, but no consensus was reached for the duration of treatment. In patients with stable or progressive disease, the experts recommended salvage therapy with posaconazole or isavuconazole. CAPM is a rare but under-reported complication of COVID-19. Although we have proposed recommendations for defining, diagnosing, and managing CAPM, more extensive research is required.

A Case Series on Neuropathogenic Nature of an Ancient Disease ----Tuberculosis.

Tuberculosis is one of the oldest diseases known to affect humans and the top cause of infectious death worldwide caused by M. tuberculosis complex. Tuberculosis may be pulmonary, extra-pulmonary or both. Nervous system tuberculosis is relatively rare and has protean nature of symptoms so poses diagnostic difficulty. Neurological manifestations of tuberculosis includes 1) intracranial 2) spinal 3) peripheral nerve tuberculosis. Central nervous system tuberculosis accounts about 5% of extra pulmonary cases and 1% all tuberculosis. MATERIAL: Here we are presenting the series of 10 cases which have wide variety of neuropathogenic nature of tuberculosis. OBSERVATION: Here we are presenting the series of 10 cases which have wide variety of neuropathogenic nature of tuberculosis. These includes 1) Tubercular cortical vein thrombosis -patient who is a known case of pulmonary tuberculosis presented with severe headache, seizure and altered behavior, MRI brain shows cortical vein thrombosis and normal coagulation profile (Review of literature shows only 4 cases). 2)Tubercular myelitis/ arachnoiditis-presented with low backache and bilateral lower limb weakness,CSF panel and MRI L S spine shows tubercular arachnoiditis/myelitis. 3)Tubercular peripheral neuropathy; patient who is a non- diabetic presented with pain abdomen and bilateral lower limb tingling and numbness with no past history of treatment with anti-tubercular drug, CECT abdomen shows ileocecal tuberculosis and NCS study shows sensory affection of lower limb nerve. 4)Tuberculoma-patient presented with severe headache, seizure and altered behavior, MRI brain shows tuberculoma. 5) and 6) are tubercular vascular infarct in 1 of these 2 cases patient was having multiple necrotic foci and few foci of cavitation in left hilar region which is extending into left inferior pulmonary vein and even reaching upto left atrium. 7) and 8) cases are pott's spine who presented with low backache. 9) and 10) are tubercular meningitis and tubercular meningitis with hydrocephalus respectively. These patients were treated according to their diagnosis and for focal neurological deficit physiotherapy was advised. Except a case of septic foci emboli from left atrium which shows moderate recovery rest all cases shows good recovery at discharge. CONCLUSION: There is paucity of literature on neuropathogenic nature of tuberculosis. In this case series we are presenting the series of 10 cases of tubercular nervous system manifestations so that it will helps to diagnose the disease as early as possible and allows us to initiate the prompt treatment so that we can mitigate the significant morbidity and mortality among survivors of nervous system tubercular disease.

Type 1 Renal Tubular Acidosis with Hypokalemic Quadriparesis in Sjogren Syndrome.

Sjogren syndrome is an autoimmune disease characterised by lymphocytic infiltration and inflammation of the exocrine glands resulting in decreased secretion of involved glands which manifests mostly as dry eye and dry mouth. The prevalence of the disease is reported to be about 10.3 per 10,000 population. It is more common in females with a male: female ratio of 16:1. Extra glandular manifestations are seen in up to 1/3rd of the cases. Renal involvement is seen in 4.9% of patients with Sjogren syndrome. MATERIAL: Here we present three cases of Sjogren Syndrome who presented to our hospital with hypokalaemic quadriparesis. OBSERVATION: On evaluation all three of the patients were found to have renal tubular acidosis type 1. None of these patients had any symptom of Sjogren syndrome before the onset of quadriparesis. All of these patients had acute onset progressive areflexic quadriparesis with involvement of facial muscles and drooping of eyelids without sensory or bladder bowel involvement. One of these patients had respiratory muscle paralysis severe enough to mandate mechanical ventilation. Arterial Blood Gas analysis and urine electrolyte analysis were suggestive of type 1 renal tubular acidosis. ANA positive in 2 of the 3 patients. Anti-SSA & anti-SSB antibodies were positive in all three patients. Supportive measures and IV fluid and electrolyte correction was done. There was complete recovery of power in all three patients and were discharged on oral medications.Renal Tubular Acidosis is characterised by inability of the nephrons to maintain physiologic acid base balance. This usually results from a defect in the tubular transport mechanisms. Distal Renal tubular acidosis (as in these patients) is further defined by an alkalotic urinary pH(>5.5) and profound hypokalemia due to impairment in H+ secretion in ditstal tubular alpha-intercalated cells. Owing to this imbalance of ionic transport in distal tubules there can be nephrocalcinosis, nephrolithiasis, rickets and severe muscle weakness. Sjogren syndrome is one of the etiologies leading to development of T1RTA.T1RTA can be the presenting feature of Sjogren Syndrome. CONCLUSION: Though a rare manifestation of the disease if can be the presenting symptom. Work up for RTA (ABG, urine electrolytes, Urine PH and osmolarity etc) in patients with hypokalaemic paresis can help establish the etiological diagnosis(ANA, anti-SSA,anti-SSB) and help prevent future relapses of the disease.

Evaluation of Simpler Criteria for Diagnosing Allergic Bronchopulmonary Aspergillosis Complicating Asthma.

Background: The modified International Society for Human and Animal Mycology (ISHAM) allergic bronchopulmonary aspergillosis (ABPA) working group (AWG) criteria lists up to five components for diagnosing ABPA in asthmatics. Whether eliminating specific components of the existing criteria would have the same diagnostic utility as the original remains unknown. Objective: To evaluate the performance of several simplified criteria for diagnosing ABPA. Methods: We compared the performance of seven new criteria (after excluding or modifying one or more of the components of the ISHAM-AWG criteria) with the modified ISHAM-AWG criteria in asthmatic subjects using latent class analysis (LCA). We also tested the performance of the newer criteria using accuracy measures against a multidisciplinary team (MDT) diagnosis of ABPA. We considered the diagnostic accuracy of the newer criteria to be acceptable if the correct classification and false-negative rates were >95% and <5%, respectively, on an MDT evaluation. Results: We analyzed data from 543 asthmatic subjects (58.8% women; mean age, 36.8 years). Using LCA, the sensitivity of the A.fumigatus-specific IgE-based criteria ranged from 92-99%, while the specificity varied between 92% and 100%. The MDT diagnosed ABPA in 106 (19.5%) subjects. Using MDT as the reference standard, the correct classification and false-negative rates were >95% for three of the seven and <5% for four of the seven newer criteria. Conclusions: We found several of the newly developed criteria to perform, like the modified ISHAM-AWG criteria, for diagnosing ABPA complicating asthma. A prospective study in current clinical algorithms is required for validating our observations.