Comprehensive analytics for virus-cell and cell-cell multinucleation system.

Cell-fusion mediated generation of multinucleated syncytia represent critical feature during viral infection and in development. Efficiency of syncytia formation is usually illustrated as fusion efficiency under given condition by quantifying total number of nuclei in syncytia normalized to total number of nuclei (both within syncytia and unfused cell nuclei) in unit field of view. However heterogeneity in multinucleated syncytia sizes poses challenge in quantification of cell-fusion multinucleation under diverse conditions. Taking in-vitro SARS-CoV-2 spike-protein variants mediated virus-cell fusion model and placenta trophoblast syncytialization as cell-cell fusion model; herein we emphasize wide application of simple unbiased detailed measure of virus-cell and cell-cell multinucleation using experiential cumulative distribution function (CDF) and fusion number events (FNE) approaches illustrating comprehensive metrics for syncytia interpretation.

Prevalence, Predictors, and Prognosis of Serious Infections in Takayasu Arteritis: A Cohort Study.

OBJECTIVE: To describe the incidence, risk factors, and outcomes associated with serious infections in patients with Takayasu arteritis (TA). METHODS: Serious infections, defined as infections resulting in hospitalization or death or unusual infections like tuberculosis, were identified from a cohort of patients with TA. Corticosteroid and disease-modifying antirheumatic drug (DMARD) use at the time of serious infection was noted. Demographic characteristics, clinical presentation, angiography, and disease activity at presentation, and the use of DMARDs during follow-up were compared between patients with TA with or without serious infections. Mortality in patients with TA who developed serious infections was compared to those who did not using hazard ratios (HR; with 95% CI). RESULTS: Of 238 patients with TA, 38 (16%) had developed serious infections (50 episodes, multiple episodes in 8; 3 episodes resulted in death). Among the 38 initial episodes, 11/38 occurred in those not on corticosteroids and 14/38 in those not on DMARDs. Pneumonia (n = 19) was the most common infection, followed by tuberculosis (n = 12). Patients with TA who developed serious infections vs those who did not had higher disease activity at presentation (active disease 97.4% vs 69.5%, mean Indian Takayasu Arteritis Activity Score 2010 12.7 (SD 7.3) vs 10.2 (SD 7.0), mean Disease Extent Index in Takayasu Arteritis 11.2 (SD 6.1) vs 8.8 (SD 6.1) and were more frequently initiated on corticosteroids or DMARDs. HRs calculated using exponential parametric regression survival-time model revealed increased mortality rate in patients with TA who developed serious infections (HR 5.52, 95% CI 1.75-17.39). CONCLUSION: Serious infections, which occurred in the absence of immunosuppressive treatment in approximately one-fifth of patients with TA, were associated with increased mortality in patients with TA.

Physiological and Anesthetic Considerations of Safe and Optimal Pneumoperitoneal Pressures for Laparoscopic Surgeries in Children.

Context: In the era of minimally invasive surgeries, pediatric laparoscopic surgeries are now becoming the standard of care. Aim: In this study, we aim to determine the safe and optimal pneumoperitoneal pressures (PPs) for laparoscopic surgery in children aged 1-5 years, along with the technical ease for the surgeon. Settings and Design: Prospective, randomized, single-blinded study was conducted at SGPGI Lucknow. Materials and Methods: Children aged 1-5 years were randomized into Group I (n = 24): PP = 6-8 mmHg and Group II: (PP) = 9-10 mmHg. Hemodynamic, ventilatory, and blood gas changes were measured before CO2 insufflation (T0), 20 min after insufflation (T1), before desufflation (T2), and 10 min after desufflation (T3). Surgeon's technical ease of surgery, postoperative pain, the requirement of rescue analgesia, time to resume feeding, and complications were recorded and analyzed. Statistical Analysis Used: Paired t-test, Mann-Whitney test, and Wilcoxon signed-rank test were used for nonparametric/parametric data. Chi-square/Fisher's test was used for nominal data. Results: Partial pressure of CO2 (PaCO2) was significantly higher in Group II at T1, T2, and T3, requiring frequent changes in ventilatory settings. Postoperative pain scores were higher in Group II at 1, 6, and 12 h, requiring rescue analgesia. Surgeon's scores and hemodynamics were similar in both groups. Conclusions: Higher PP in Group II caused significant changes in PaCO2, end-tidal CO2, and postoperative pain requiring rescue analgesia, but blood gas changes were clinically insignificant and there were no significant changes in hemodynamic parameters. Since the surgeon's ease of performing surgery was similar in both groups, we recommend that laparoscopy in children aged 1-5 years can be started with lower PPs of 6-8 mmHg, which can be increased if needed based on the surgeon's comfort and the patient's body habitus.

Incidence of Different Characters of Neuropathic Pain in Cancer Patients Coming to Tertiary Care Centre in North India Over A Period of 1 Year - An Observational Study.

Objectives: Pain is classified as nociceptive, neuropathic, or nociplastic. Neuropathic pain presents as variable phenotypes (characters) based on specific aetiology and pathophysiology. This study aimed to find out among cancer patients the incidence of different phenotypes of neuropathic pain and form specific phenotypic clusters based on the underlying neurophysiology and association of sensory profile with various organ systems - A prospective observational study. Materials and methods: The Institutional Ethical Committee clearance (IEC code: 2020-49-MD-EXP-15) https://ctri.nic.in/Clinicaltrials/showallp.php?mid1=44886&EncHid=88651.15716&userName=CTRI/2020/09/027964 approval was obtained. After written and informed consent, patients of age group 18-80 years, registering in the pain and palliative outpatient department or radiotherapy department with complaints of pain and not taking any anti-neuropathic pain medications, were enrolled. They were assessed using Leeds assessment of neuropathic symptoms and signs (LANSS) pain score, and a score of >12 was eligible for assessment of neuropathic pain phenotypes. Results: Out of 210 cancer patients complaining of pain, a neuropathic component with LANSS >12 was found in 73 (34.76%). The most predominant phenotypes, allodynia> tingling> pricking = burning, were found in 72.60%, 56.16%, and 43.84% of patients, respectively. Phenotypes were clustered into Nodes 1 and 2 based on clinically significant separation of phenotypes. Node 1 had neuropathic pain of spontaneous origin found predominantly in gastrointestinal tract (GIT) and genitourinary tract (GUT) cancers. Node 2 had stimulus-evoked negative and positive characters which occurred in head and neck, thoracic, and spinal metastatic cancers. Conclusion: Careful patient assessment reveals the incidence of neuropathic pain in 34.76%; allodynia and tingling astable the most prominent phenotypes. Broadly, sensory characters were clustered into spontaneous and stimulus-evoked sensations with GIT and GUT cancers presenting with Node 1 symptoms.

Increased mortality rate in Takayasu arteritis is largely driven by cardiovascular disease-a cohort study.

OBJECTIVES: To analyze the risk, causes, and predictors of mortality in Takayasu arteritis (TAK). METHODS: Survival was assessed in a cohort of patients with TAK using Kaplan-Meier curves. Age- and sex-standardized mortality ratio (SMR = observed: expected deaths) for TAK were calculated by applying age- and sex-specific mortality rates for the local population to calculate expected deaths. Hazard ratios (HR with 95%CI) for predictors of mortality based on demographic characteristics, presenting features, baseline angiographic involvement, disease activity, number of immunosuppressive medications used, procedures related to TAK, and any serious infection were calculated using Cox regression or exponential parametric regression models. RESULTS: Among 224 patients with TAK (159 females, mean follow-up duration 44.36 months), survival at 1, 2, 5, and 10 years was 97.34%, 96.05%, 93.93%, and 89.23%, respectively. Twelve deaths were observed, most of which were due to cardiovascular disease (heart failure, myocardial infarction, stroke). Mortality risk was significantly higher with TAK (SMR 17.29, 95%CI 8.95-30.11) than the general population. Earlier age at disease onset (HR 0.90, 95%CI 0.83-0.98; or pediatric-onset vs adult-onset disease, HR 5.51, 95%CI 1.57-19.32), higher disease activity scores (ITAS2010: HR 1.15, 95%CI 1.05-1.25, DEI.TAK: HR 1.18, 95%CI 1.08-1.29), any serious infections (HR 5.43, 95%CI 1.72-17.12), heart failure (HR 7.83, 95%CI 2.17-28.16), or coeliac trunk involvement at baseline (HR 4.01, 95%CI 1.26-12.75) were associated with elevated mortality risk. CONCLUSION: Patients with TAK had an elevated risk of mortality as compared with the general population. Cardiovascular disease was the leading cause of death in TAK.

Paediatric-onset Takayasu's arteritis associates with worse survival than adult-onset Takayasu's arteritis. A matched retrospective cohort study.

OBJECTIVES: A subset of Takayasu's arteritis (TAK) begins in the paediatric age group (≤18 years). Differences in prognosis between paediatric-onset and adult-onset TAK are unclear. We compared the differences in the presentation and survival between paediatric-onset and adult-onset TAK in our cohort of TAK. METHODS: From a retrospective cohort of TAK, clinical presentation, angiographic features, treatments received, disease activity, and survival were compared between paediatric-onset and adult-onset TAK. Multivariable-adjusted logistic regression models were used to compute adjusted odds ratio (aOR) with 95% confidence intervals (95%CI) for paediatric-onset vs. adult-onset TAK. Hazard ratios (HR, with 95%CI) for mortality with paediatric-onset vs adult-onset TAK (crude, adjusted for prognostic covariates or differences in presentation) and propensity score-matched survival analyses were estimated. RESULTS: Among 56 paediatric-onset and 135 adult-onset TAK, chest pain (aOR 3.21, 95%CI 1.06-9.74), heart failure (aOR 3.16, 95%CI 1.05-9.53), headache (aOR 2.60, 95%CI 1.01-6.74), ascending aorta (aOR 3.02, 95%CI 1.04-8.80) and left renal artery involvement (aOR 2.45, 95%CI 1.04-5.80) were more frequent in paediatric-onset TAK. Despite similar longitudinal patterns of disease activity and glucocorticoid or disease-modifying antirheumatic drug (DMARD) use, mortality was higher for paediatric-onset TAK (HR, unadjusted 6.13, 95%CI 1.51-24.91; adjusted for prognostic covariates gender, diagnostic delay, baseline disease activity, number of conventional and biologic/targeted synthetic DMARDs used, 4.97, 95%CI 1.20-20.58; adjusted for differences between groups 5.54, 95%CI 1.22-25.09; after propensity-score matching for prognostic covariates, 54 pairs, log-rank p-value 0.026). CONCLUSIONS: Considering the greater mortality risk, greater vigilance is required while managing paediatric-onset TAK.

Analysis of cellular and cell free mitochondrial DNA content and reactive oxygen species levels in maternal blood during normal pregnancy: a pilot study.

BACKGROUND: Alterations in mitochondrial signatures such as mitochondrial DNA (mtDNA) content in maternal blood have been linked to pregnancy-related complications. However, changes in maternal mtDNA content, their distribution and associated signaling during normal pregnancies are not clear; which could suggest their physiological role in maternal adaptation to pregnancy related changes and a reference threshold. THE AIM OF THIS STUDY: to assess the distribution of mtDNA in peripheral blood and their association with circulatory ROS levels across different trimesters of healthy pregnancy. METHODS: In this pilot cross sectional study, blood samples of normal pregnant women from each trimester (total = 60) and age-matched non-pregnant (NP) women as control group (n = 20) were analyzed for a) the relative distribution of mtDNA content in cellular and cell free (plasma) fractions using relative quantitative polymerase chain reaction (qPCR) and b) the levels of circulating reactive oxygen species (ROS) by measurement of plasma H2O2. The results were compared between pregnant and NP groups and within trimesters for significant differences, and were also analyzed for their correlation between groups using statistical methods. RESULTS: While, we observed a significant decline in cellular mtDNA; plasma mtDNA was significant increased across all trimesters compared to NP. However, from comparisons within trimesters; only cellular mtDNA content in 3rd trimester was significantly reduced compared to 1st trimester, and plasma mtDNA did not differ significantly among different trimesters. A significantly higher level of plasma H2O2 was also observed during 3rd trimester compared to NP and to 1st trimester. Correlation analysis showed that, while cellular mtDNA content was negatively correlated to plasma mtDNA and to plasma H2O2 levels; plasma mtDNA was positively correlated with plasma H2O2 content. CONCLUSIONS: This study suggested that normal pregnancy is associated with an opposing trend of reduced cellular mtDNA with increased circulatory mtDNA and H2O2 levels, which may contribute to maternal adaptation, required during different stages of pregnancy. Estimation of mtDNA distribution and ROS level in maternal blood could show mitochondrial functionality during normal pregnancy, and could be exploited to identify their prognostic/ diagnostic potential in pregnancy complications.

Quantitative assessment of brainstem distortion in vestibular schwannoma and its implication in occurrence of hydrocephalus.

PURPOSE: Anatomical distortion directly affects the clinical status of patients with vestibular schwannomas (VSs). It may vary for a given tumor size due to variability in posterior fossa anatomy. We aimed to quantitatively assess brainstem distortion (BSD) and review its role in occurrence of hydrocephalus associated with VSs. METHODS: Sixty-six patients with small (<3 cm, n= 8; 12.1%); large (3-4 cm; n= 26; 39.4%) and giant (>4 cm; n= 32; 48.5%) VSs were included. Cystic VSs were excluded. Tumor size, tumor-extent, linear displacement (LD; distance between line bisecting pons (line 1) and posterior fossa midline (line 2)) and angular distortion (AD; angle subtended between lines 1 and 2) in axial-T2-MRI section through pons, and their effect on hydrocephalus were assessed. RESULTS: Significant BSD occurred in a younger age (p value = .004/.003), larger-sized tumor (p value = .001/.002), hydrocephalus (p value = .001/.001), trigeminal (V) nerve palsy (p value = .004/.003) and long tract signs (p value = .001/.034). Tumors crossing midline had significant association with hydrocephalus (p value = .003). LD increased progressively even for 4-5 cm-sized tumors while AD stabilized. Receiver operating characteristic (ROC) curve revealed that diagnostic accuracy of LD (area under the ROC curve (AUROC): 78.9% (95% CI: 67.2%, 90.5%, p < .001)), AD (AUROC:77.6% (95% CI:65.8%, 89.5%, p < .001)) and LD × AD (AUROC:80.3% (95% CI: 69.2%, 91.2%, p < .001)) for predicting occurrence of hydrocephalus was better than tumor size (AUROC: 66.7% (95% CI: 53.5%, 79.9%, p < .05). Cut-off values of LD and AD for predicting occurrence of hydrocephalus were 6.25 mm and 14.6°, respectively. Hydrocephalus was significantly more when both LD was greater than  6.25 mm and AD was greater than 14.5° (p value = .034). The role of LD and AD in influencing hydrocephalus was greater than categorization based on tumor size (Spearman's correlation coefficient: 0.535 and 0.248, respectively). Hydrocephalus occurred at a lesser cut-off value of LD and AD when compared to long tract signs. CONCLUSIONS: LD and AD values in VSs have a significantly greater influence in the development of hydrocephalus compared to tumor size, and may aid, more reliably, in the prediction of hydrocephalus.

Impact of COVID-19 pandemic on cancer surgery: Patient's perspective.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has impacted cancer care globally. The aim of this study is to analyze the impact of COVID-19 on cancer healthcare from the perspective of patients with cancer. METHODS: A cross-sectional survey was conducted between June 19, 2020, to August 7, 2020, using a questionnaire designed by patients awaiting cancer surgery. We examined the impact of COVID-19 on five domains (financial status, healthcare access, stress, anxiety, and depression) and their relationship with various patient-related variables. Factors likely to determine the influence of COVID-19 on patient care were analyzed. RESULTS: A significant adverse impact was noted in all five domains (p = < 0.05), with the maximal impact felt in the domain of financial status followed by healthcare access. Patients with income levels of INR < 35 K (adjusted odds ratio [AOR] = 1.61, p < 0.05), and 35K- 100 K (AOR = 1.96, p < 0.05), married patients (AOR = 3.30, p < 0.05), and rural patients (AOR = 2.82, p < 0.05) experienced the most adverse COVID-19-related impact. CONCLUSION: Delivering quality cancer care in low to middle-income countries is a challenge even in normal times. During this pandemic, deficiencies in this fragile healthcare delivery system were exacerbated. Identification of vulnerable groups of patients and strategic utilization of available resources becomes even more important during global catastrophes, such as the current COVID-19 pandemic. Further work is required in these avenues to not only address the current pandemic but also any potential future crises.

Should serial monitoring of procalcitonin be done routinely in critically ill patients of ICU: A systematic review and meta-analysis.

Sepsis is a life-threatening condition with dysregulated host response to infection. It is a major determinant of mortality in the intensive care unit (ICU). Procalcitonin (PCT) is widely investigated for prognosis in patients with sepsis. Most of the studies have cited that elevated PCT concentrations and PCT non-clearance are associated with poor outcomes in patients with sepsis and some studies have cited as having no additional benefit. Most of the studies have evaluated single PCT measurement and correlated with prognosis and outcome in septic patients. Limited literature is there about serial PCT levels and its impact on the outcome of patients with sepsis. We searched literature through PubMed, Embase, Web of Knowledge, and the Cochrane Library from 2007 to 2017 and present a systematic review and meta-analysis of studies evaluating the utility of serial measurement of PCT for prognosis in critically ill patients. Articles that assessed PCT non-clearance as a marker of mortality data were included. The primary objective of this meta-analysis was to pool the results of all the available studies on serial PCT non-clearance as a mortality predictor and formulate overall area under receiver operating curve (AUROC). To find out the overall proportion of mortality in PCT non-clearance was our secondary objective. To detect the mortality using PCT non-clearance, ROC curve analysis was done. Area under curve (AUC) of the studies was varying between 0.52 and 0.86. Overall AUC was observed 0.711 (95% confidence interval (CI): 0.662-0.760) under fixed effect model and 0.708 (95% CI: 0.648-0.769) under random effect model. There was moderate variation among the studies, i.e., I2 50.80% (95% CI: 0.00-80.42%). The overall proportion of mortality was 37.54% with much heterogeneity (I2 88.24%) among the studies. PCT non-clearance is a fair predictor of mortality. Further studies are needed to define optimal cut off point for PCT non-clearance in ICU patients with sepsis.

Comparative evaluation of success of ultrasound-guided internal jugular vein cannulation using needle with guard: A randomized, controlled study.

BACKGROUND AND AIMS: We devised a guard which can be slid and fixed over the central venous puncture needle at a desired length (measured through ultrasound) preventing the needle from penetrating deeper into the skin beyond this guard. This randomized, single blinded, controlled study was designed to evaluate the success of ultrasound guided internal jugular vein (IJV) cannulation using measured guided needle with guard in terms of success and occurrence of complications. MATERIAL AND METHODS: After ethical approval and written informed consent from the patients ultrasound-guided right-sided IJV cannulation was done with a conventional puncture needle (length of 6.4 cm) in the control group (n = 210) and with a conventional puncture needle with a guard fixed proximal to the bevel at a distance equal to the distance between the skin entry point and the midpoint of IJV measured with the help of USG in the study group (n = 210). The primary outcome studied was the number of attempts for successful cannulation. The secondary outcomes studied were complications and ease of cannulation. RESULTS: 419 patients were randomized into control (n = 209) and study groups (210). Successful IJV cannulation in the first attempt (primary endpoint) in the study group was significantly higher compared to the control group (98.6 vs. 85.7%, P = 0.007). Posterior venous wall puncture was reduced in the study group, that is, 0.5% (1/210) compared to control group, that is, 8.61% (18/209) (P = 0.001). Common carotid artery puncture was 7.18% (15/209) in control group and 0% (0/210) in study group (P = 0.001). Operators rated better ease in study group (P < 0.001). CONCLUSIONS: The use of measured guided needle with guard significantly improved the accuracy, success and ease of USG guided IJV cannulation and decreased complications.

Deletion of insulin receptor in the proximal tubule and fasting augment albumin excretion.

The contribution of proximal tubules (PT) to albumin uptake is now well recognized, however, its regulation is understudied area. There are reports suggesting that insulin resistance is associated with the development of albuminuria in nondiabetic individuals. We have previously reported reduced insulin receptor (IR) expression in renal-tubular-epithelial cells, including PT in various models of insulin resistance. However, the effect of a physiological fall in insulin levels and the role for IR in PT in tubular albumin uptake is not clear. To address these gaps in our understanding, we estimated urine excretion and renal uptake of albumin in fasted and fed C57Bl/6 mice injected with fluorescein isothiocyanate (FITC)-albumin (5 µg/mL/kg body weight, intraperitoneal, n = 6 per group). In addition, we compared spot urine analysis from 33 clinically healthy humans after overnight fasting (when insulin levels are lower than in the fed state) and then at 2 hours after 75 g oral glucose challenge (postprandial). Fasted mice had attenuated renal uptake of FITC-albumin and higher excretion in urine, relative to fed mice ( P = 0.04). Moreover, a significant drop in urine albumin-to-creatinine ratio (ACR) and urine albumin concentration (UAC) was observed in the postprandial state in these subjects ( P = 0.001 and P = 0.017, for ACR and UAC, respectively). The drop was negatively associated with postprandial blood glucose levels (ρ = -0.36, P = 0.03 for ΔUAC and ρ = -0.34, P = 0.05 for ΔACR). To test the role of IR in PT, we analyzed 24-hour urine albumin excretion in male mice with targeted deletion of IR from PT (insulin receptor knockout [IRKO]) and their wild-type (WT) littermates ( n = 7 per group). IRKO mice had significantly higher 24-hour urine albumin excretion relative to WT. Moreover, kidneys from KO mice revealed reduced expression of megalin and cubulin proteins in the PT relative to the WT. We also demonstrated insulin (100 nM) induced albumin internalization in human proximal tubule cells (hPT) and this effect of insulin was attenuated in hydroxy-2-naphthalenylmethylphosphonic acid (100 µM), a tyrosine kinase inhibitor, pretreated hPT. Our findings revealed albumin excretion was attenuated by glucose administration to fasting individuals implying a regulatory role for insulin in PT albumin reabsorption. Thus albuminuria associated with insulin resistance/diabetes may relate not only to glomerular dysfunction but also to impairment in insulin-mediated reabsorption.

Effect of Prone Positioning on Intraocular Pressure in Patients With Acute Respiratory Distress Syndrome.

OBJECTIVES: To evaluate the effect of prolonged duration of prone position (with head laterally rotated) on intraocular pressure in acute respiratory distress syndrome patients. DESIGN: Prospective observational study. SETTING: University hospital ICU. PATIENTS: Twenty-five acute respiratory distress syndrome patients, age 60 years (51-67 yr), Sequential Organ Failure Assessment score 10 (10-12), PaO2/FIO2 ratio of 90 (65-120), and all in septic shock. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Intraocular pressure (in mm Hg) measured by hand-held applanation tonometer, at different time points. Before prone (in both eyes): at 30-45° head-end elevation position (THE pre-prone), in supine position just before turning prone (Tsupine pre-prone); during prone (in nondependent eye): at 10 minutes (T10 prone), 30 minutes (T30 prone), and at just before end of prone session (Tend-prone). After end of prone session (both eyes): at 5 minutes (T5 supine post-prone), 10 minutes (T10 HE post-prone), 15 minutes (T15 HE post-prone), and 30 minutes (T30 HE post-prone). Median duration of prone position was 14 hours (12-18 hr). Median intraocular pressure increased significantly (p ≤ 0.001) in both eyes. In dependent eye, from 15 (12-19) at THE pre-prone to 24, 21, 19, and 16 at T5 supine post-prone, T10 HE post-prone, T15 HE post-prone, and T30 HE post-prone respectively, whereas in nondependent eye from 14 (12-18.5) at THE pre-prone to 23, 25, 32, 25, 22, 20, and 17 at T10 prone, T30 prone, Tend-prone, T5 supine post-prone, T10 HE post-prone, T15 HE post-prone, and T30 HE post-prone respectively. Bland-Altman plot analysis showed significant linear relationship (r = 0.789; p ≤ 0.001) with good agreement between rise in mean intraocular pressure of the both eyes (dependent eye and nondependent eye) with their paired differences after the end of different duration of prone session (T5 supine post-prone). CONCLUSIONS: There is significant increase in intraocular pressure due to prone positioning among acute respiratory distress syndrome patients. Intraocular pressure increases as early as 10 minutes after proning, with increasing trend during prone position, which persisted even at 30 minutes after the end of post prone session although with decreasing trend.

Early pH Change Predicts Intensive Care Unit Mortality.

AIM OF THE STUDY: Metabolic acidosis is associated with increased mortality in critically ill patients. We hypothesized that early correction of acidosis of presumed metabolic origin results in improved outcomes. PATIENTS AND METHODS: We conducted a prospective, observational study from February 2015 to June 2016 in a 12 bed mixed intensive care unit (ICU) of a 1000 bed tertiary care hospital in the north of India. ICU patients aged above 18 years with an admission pH ≥7.0 to <7.35 of presumed metabolic origin were included. Arterial blood gas parameters including pH, PaO2, PaCO2, HCO3 -, Na+, K+, Cl-, anion gap (AG), base excess, and lactate at 0, 6, and 24 h along with other standard laboratory investigations were recorded. The primary outcome was to assess the impact of early pH changes on mortality at day 28 of ICU. RESULTS: A total of 104 patients with 60.6% males and 91.3% medical patients were included in the study. Sepsis of lung origin (60.6%) was the predominant etiology. By day 28, 68 (65.4%) patients had died. Median age was 49.5 years, weight 61.7 kg, Sequential Organ Failure Assessment, and Acute Physiologic and Chronic Health Evaluation II scores were 16 and 12, respectively. Nonsurvivors had a higher vasopressor index (P < 0.01), lactate and central venous oxygen saturation (P < 0.05), and lower pH (P < 0.05). A pH correction/change of ≥1.16% during the first 24 h had the best receiver operating characteristic for predicting survival at day 28, with area under the curve (95% confidence interval, 0.72 [0.62-0.82], P < 0.05) compared to HCO3 -, BE, lactate, and AG. CONCLUSIONS: Metabolic acidosis is associated with higher mortality in ICU. The rate of change in pH may better predict ICU mortality than other metabolic indices.

Comparison of Hemodynamic Monitoring between Transesophageal Doppler and Ultrasonography-Guided Inferior Vena Cava Distensibility in Supine versus Prone Position: A Pilot Study.

INTRODUCTION: Lung-protective ventilation strategy and prone positioning are the strategies practiced to manage patients suffering from acute respiratory distress syndrome (ARDS). Inferior Vena Cava Distensibility (dIVC) Index has been used for predicting fluid responsiveness (FR) in supine position. We conducted this study to observe the utility of dIVC in prone position in ARDS patients and compare it with esophageal Doppler (ED) parameters. MATERIALS AND METHODS: After ethical clearance, a prospective observational pilot study was conducted in a 12-bedded tertiary care hospital. Adult ARDS patients who were treated with prone ventilation were included. Informed consent was taken from the relatives. IVC was visualized through right lateral approach both in supine and prone positions. We compared IVC distensibility and ED parameters, first in 45° head up and then in prone. FR was defined as an increase in the stroke volume of ≥15% as measured by ED. The patients with dIVC >18% were assumed to be fluid responsive. Statistical analysis was done using SPSS software version 20. RESULTS: Twenty-five patients met the inclusion criteria. ARDS was (mean P/F ratio 116.64 ± 44.76) mostly due to pulmonary etiology. Out of 25 patients, 10 patients were fluid responsive based on dIVC (cutoff >18%) in supine position. When compared to ED values after passive leg raising, dIVC had a sensitivity and specificity of 77.78% and 81.25%, respectively, in predicting FR with a moderate-to-absolute agreement between the two methods. IVC distensibility showed statistically significant negative correlation with corrected flow time (FTc) values both in supine and in prone positions. CONCLUSION: IVC variability can be observed in acute respiratory distress syndrome patients in prone position. Inferior Vena Cava Distensibility correlates with flow time in both the positions.

Correlation of Neutrophil CD64 with Clinical Profile and Outcome of Sepsis Patients during Intensive Care Unit Stay.

INTRODUCTION: Neutrophil CD64 (nCD64) has been found to identify sepsis from nonseptic patients. It is also reported to be a predictor of survival and severity of sepsis. The goal of this study was to correlate serial nCD64 with Intensive Care Unit (ICU) outcome and severity of sepsis. MATERIALS AND METHODS: A prospective observational study was conducted in 12-bedded critical care unit of a tertiary care center. Adult patients with sepsis were included in this study. Demographics, illness severity scores, clinical parameters, laboratory data, and 28-day outcome were recorded. Serial nCD64 analysis was done (on days 0, 4, and 8) in consecutive patients. RESULTS: Fifty-one consecutive patients were included in the study. Median Acute Physiology and Chronic Health Evaluation II was 16 (12-20) and mean Sequential Organ Failure Assessment was 9 (8-10). Compared to survivors, nonsurvivors had higher nCD64 on day 8 (P = 0.001). nCD64 was higher in the septic shock group compared to sepsis group on days 0 and 8 (P < 0.05). Survivors showed improving trend of nCD64 over time while nonsurvivors did not. This trend was similar in the presence or absence of septic shock. nCD64 count was a good predictor of the septic shock on day 0 (area under the curve [AUC] = 0.747, P = 0.010) and moderate predictor at day 8 (AUC = 0.679, P = 0.028). CONCLUSION: Monitoring serial nCD64 during ICU stay may be helpful in determining the clinical course of septic patients.

Dexmedetomidine for prevention of early postoperative catheter-related bladder discomfort in voluntary kidney donors: Prospective, randomized, double-blind, placebo-controlled trial.

BACKGROUND AND AIMS: Catheter-related bladder discomfort (CRBD) has started to gain recognition as a problem in early postoperative care. Dexmedetomidine reduces bladder contractility via M3 muscarinic receptor antagonism and α-2 receptor agonism, apart from its concomitant therapeutic benefits, such as sedation and sympatholysis, in a postoperative period. We, therefore, evaluated the efficacy of dexmedetomidine in reducing incidence and severity of CRBD. MATERIAL AND METHODS: This prospective, randomized, double-blind, placebo-controlled trial done on 110 voluntary kidney donors for live related kidney transplantations were planned for laparoscopic donor nephrectomy. The donors were of ages 18-60 years, American Society of Anesthesiologists physical status I and II of either sex. The control group received 20 ml normal saline (NS) intravenous (IV) infusion over 15 min, whereas the dexmedetomidine group received dexmedetomidine 1 µg/kg made in 20 ml NS as IV infusion over 15 min. The incidence and severity of CRBD were recorded as primary endpoints up to 12 h in early postoperative period. The incidence of bladder discomfort was analysed by Fisher's exact test and severity of bladder discomfort by Mann Whitney U test. RESULTS: The incidence of CRBD on arrival at postoperative care unit was 18% in dexmedetomidine group compared to 42% in control group (P < 0.05). The incidence and severity of CRBD reduced in dexmedetomidine group at 0, 2, and 4 h compared with control group (P < 0.05). CONCLUSIONS: Dexmedetomidine 1 µg/kg administered IV to patients 30 min before extubation reduces the incidence and severity of CRBD in early postoperative settings with no adverse effects.

Poorly differentiated thyroid cancer: Clinical, pathological, mutational, and outcome analysis.

INTRODUCTION: Poorly differentiated thyroid cancer (PDTC) remains a challenge not only for pathologists and surgeons because of the difficulties associated with the diagnostic process and the compelling need for difficult thyroidectomy, but it is also of high clinical relevance because it is responsible for mortality in non-anaplastic follicular cell-derived thyroid cancer. MATERIALS AND METHODS: Cases of PDTC within a 30-year period were reviewed by two independent pathologists. Histological features like atypical mitosis, necrosis, capsular, and vascular invasion were studied. Mutation analysis was done for BRAF, RET/PTC, RAS, and PI3KCA, and P53 was performed using immunohistochemistry. RESULTS: There were 39 patients with a median age of 53 years; 14 patients were more than 55 years of age. At presentation, 38.4% had compressive features and the median tumor size was 9 cm. At presentation, 67.7% had an extrathyroidal extension (ETE). R0 resection was achieved in 41%, with 12 cases resulting in a difficult thyroidectomy. Necrosis was seen in 65.7% and mitosis in 73.3% with well-differentiated components in 41%. The commonest mutation was RAS (23.1%). Survival was higher in the operable group (54.26, 95% confidence interval [CI]: 30.83-77.70 vs. 20.25, 95% CI: 0-54.07) months, respectively; however, 10-year survival was only 5% and only the tumor size and presence of mitosis were independent risk factors. CONCLUSION: PDTC presents with worrisome features like large size, ETE, and rapid growth. Aggressive surgical resection with extended/radical thyroidectomy may result in better loco-regional control and improved survival. RAS was the frequent mutation detected. It is worthwhile to identify prognostic factors that can predict the course of PDTC.

Significance of histopathological features in the diagnosis of Budd-Chiari syndrome on liver biopsies.

Background: Budd-Chiari syndrome (BCS) requires a constellation of clinical, imaging, and histological findings for diagnosis. Liver biopsy serves as a tool for confirming the diagnosis, even though the histological characteristics are not pathognomonic. Aims: To determine which constellation of morphologic findings could aid in establishing a diagnosis of BCS in clinically suspected cases. Materials and Methods: A 5-year retrospective observational study was conducted. The clinical, laboratory, and histological findings of liver biopsies in patients with a clinical diagnosis of BCS were studied. Cases were segregated into two groups on the basis of the number of histological features present. A scoring system was then devised to assess the efficacy of the histological findings in diagnosing BCS. Statistical Analysis Used: The continuous variables were compared using the Mann-Whitney U-test, and categorical variables were compared using the Fisher-exact test. Results: The common histopathological findings were the presence of red blood cells in the space of disse (100%), peri-portal fibrosis (97.1%), sinusoidal dilation (97.1%), portal inflammation (67.6%), centrilobular necrosis (61.8%) and pericellular/sinusoidal fibrosis (61.8%). Comparison between the two groups showed that centrilobular necrosis, lobular inflammation, portal inflammation, central vein fibrosis, and pericellular/sinusoidal fibrosis were significant parameters. No correlation was found between the clinical and laboratory parameters and the two groups. Conclusions: The liver biopsy features in BCS are often nonspecific, and no single feature in isolation is characteristic. A constellation of features (centrilobular necrosis, lobular inflammation, portal inflammation, central vein fibrosis, and pericellular/sinusoidal fibrosis), when present together, indicate the possibility of BCS.

Impact of COVID-19 Pandemic on People with Locomotor Disability in North India: A Cross-Sectional Analysis.

OBJECTIVE: To assess, analyse, and infer the impact of the coronavirus disease 2019 (COVID-19) pandemic on people living with locomotor disability in North India. METHODS: Patients with locomotor disabilities who met the inclusion criteria received a questionnaire that had already undergone testing and validation. It covered topics highlighting the effect of the pandemic on general health, financial burden, psychological and mental health, social life and behaviour, disability and comorbidity management, transportation, and healthcare accessibility during the pandemic. In order to gauge the pandemic's effects on the population of people with locomotor disabilities, the answers to the questions were collected and analyzed. RESULTS: The COVID-19 pandemic has adversely affected people living with locomotor disability, ranging from loss of wages and financial crisis to anxiety, depression and lack of sleep. People with disabilities had limited reach to health and community services that were vital for them, including basic life and functional needs, besides risks of mistreatment and other psychological consequences. CONCLUSION: This analysis suggests that the root cause of pandemic disparities is the lack of disability-inclusive planning and, more significantly, the pre-existing socioeconomic disparities and challenges that disabled people have been experiencing for a long time. We suggest that unambiguous public health and policy responses should be incorporated, and health, social participation, and socioeconomic disparity causes for disabled people should be addressed in tandem.