Quantitative comparison of cell-cell detachment force in different experimental setups.

We compare three different setups for measuring cell-cell adhesion. We show that the measured strength depends on the type of setup that is used. For identical cells different assays measure different detachment forces. This can be understood from the fact that cell-cell detachment is a global property of the system. We also analyse the role of external force and line tension on contact angle and cell-cell detachment. Comparison with the experiments suggest that viscous forces play an important role in the process. We dedicate this article to Fyl Pincus who for many of us is an example to be followed not only for outstanding science but also for a marvelous human behavior.

Unilateral Traumatic Adrenal Hemorrhage with Shock.

Trauma to the adrenal glands is very rare. The variation in clinical manifestations is marked and markers for its diagnosis being limited, makes it tough to be diagnosed. Computed tomography remains the gold standard for detecting this injury. Prompt recognition and the potential for mortality with adrenal insufficiency can provide the best guidance for the treatment and care of the severely injured. We present a case of a 33-year-old trauma patient who was not responding to the management of his shock. He was finally found to have a right adrenal haemorrhage leading to adrenal crisis. The patient was resuscitated in the Emergency Department but succumbed 10 days post admission.

National Early Warning Score 2 is superior to quick Sequential Organ Failure Assessment in predicting mortality in sepsis patients presenting to the emergency department in India: A prospective observational study.

Background: High in-hospital mortality in sepsis patients remains challenging for clinicians worldwide. Early recognition, prognostication, and aggressive management are essential for treating septic patients. Many scores have been formulated to guide clinicians to predict the early deterioration of such patients. Our objective was to compare predictive values of quick Sequential Organ Failure Assessment (qSOFA) and National Early Warning Score 2 (NEWS2) with respect to in-hospital mortality. Methods: This prospective observational study was conducted in a tertiary care center in India. Adults with suspected infection with at least two Systemic Inflammatory Response Syndrome criteria presenting to the emergency department (ED) were enrolled. NEWS2 and qSOFA scores were calculated, and patients were followed until their primary outcome of mortality or hospital discharge. The diagnostic accuracy of qSOFA and NEWS2 for predicting mortality was analyzed. Results: Three hundred and seventy-three patients were enrolled. Overall mortality was 35.12%. A majority of patients had LOS between 2 and 6 days (43.70%). NEWS2 had higher area under curve at 0.781 (95% confidence interval [CI] (0.59, 0.97)) than qSOFA at 0.729 (95% CI [0.51, 0.94]), with P < 0.001. Sensitivity, specificity, and diagnostic efficiency to predict mortality by NEWS2 were 83.21% (95% CI [83.17%, 83.24%]); 57.44% (95% CI [57.39%, 57.49%]); and 66.48% (95% CI [66.43%, 66.53%]), respectively. qSOFA score had sensitivity, specificity, and diagnostic efficiency to predict mortality of 77.10% (95% CI [77.06%, 77.14%]); 42.98% (95% CI [42.92%, 43.03%]); and 54.95% (95% CI [54.90%, 55.00%]), respectively. Conclusion: NEWS2 is superior to qSOFA in predicting in-hospital mortality for sepsis patients presenting to the ED in India.

Volume regulation in adhered cells: Roles of surface tension and cell swelling.

The volume of adhered cells has been shown experimentally to decrease during spreading. This effect can be understood from the pump-leak model, which we have extended to include mechano-sensitive ion transporters. We identify a novel effect that has important consequences on cellular volume loss: cells that are swollen due to a modulation of ion transport rates are more susceptible to volume loss in response to a tension increase. This effect explains in a plausible manner the discrepancies between three recent, independent experiments on adhered cells, between which both the magnitude of the volume change and its dynamics varied substantially. We suggest that starved and synchronized cells in two of the experiments were in a swollen state and, consequently, exhibited a large volume loss at steady state. Nonswollen cells, for which there is a very small steady-state volume decrease, are still predicted to transiently lose volume during spreading due to a relaxing viscoelastic tension that is large compared with the steady-state tension. We elucidate the roles of cell swelling and surface tension in cellular volume regulation and discuss their possible microscopic origins.

Rapid Thrombolysis Protocol: Results from a Before-and-after Study.

Objective: Intravenous thrombolysis within 4.5 hours from time of onset has proven benefit in stroke. Universal standard for the door-to-needle (DTN) time is within 60 minutes from the time of arrival of patients to the emergency department. Our rapid thrombolysis protocol (RTPr) was developed with an aim to reduce the DTN time to a minimum by modifying our stroke post-intervention processes. Materials and methods: This before-and-after study was conducted at a single center on patients who received intravenous thrombolysis in the emergency department. Consecutive patients who were thrombolysed using our RTPr (post-intervention group) were compared to the pre-intervention group who were thrombolysed before the implementation of the protocol. The primary outcomes were DTN time, time to recovery, and modified ranking score (mRS) on discharge. Secondary outcomes were mortality, symptomatic intracerebral hemorrhage, and hospital and intensive care unit length of stay. Results: Seventy-four patients were enrolled in each group. Mean DTN time in pre- and post-intervention group was 56.15 minutes (95% CI 49.98-62.31) and 34.91 minutes (95% CI 29.64-40.17) (p <0.001), respectively. In pre-intervention and post-intervention groups, 43.24% (95% CI 32.57-54.59) and 41.89% (95% CI 31.32-53.26) patients, respectively, showed neurological recovery in 24 hours. About 36.49% (95% CI 26.44-47.87) in pre-intervention group and 54.05% (95% CI 42.78-64.93) in post-intervention group had discharge mRS 0-2. Conclusion: The RTPr can be adapted by clinicians and hospitals to bring down the DTN times and improve outcomes for stroke patients. How to cite this article: Verma A, Sarda S, Jaiswal S, Batra A, Haldar M, Sheikh WR, et al. Rapid Thrombolysis Protocol: Results from a Before-and-after Study. Indian J Crit Care Med 2022;26(5):549-554.

A mechano-osmotic feedback couples cell volume to the rate of cell deformation.

Mechanics has been a central focus of physical biology in the past decade. In comparison, how cells manage their size is less understood. Here, we show that a parameter central to both the physics and the physiology of the cell, its volume, depends on a mechano-osmotic coupling. We found that cells change their volume depending on the rate at which they change shape, when they spontaneously spread or when they are externally deformed. Cells undergo slow deformation at constant volume, while fast deformation leads to volume loss. We propose a mechanosensitive pump and leak model to explain this phenomenon. Our model and experiments suggest that volume modulation depends on the state of the actin cortex and the coupling of ion fluxes to membrane tension. This mechano-osmotic coupling defines a membrane tension homeostasis module constantly at work in cells, causing volume fluctuations associated with fast cell shape changes, with potential consequences on cellular physiology.

Increased Length of Stay of Critically Ill Patients in the Emergency Department Associated with Higher In-hospital Mortality.

OBJECTIVES: Emergency department (ED) length of stay (LOS) is defined as the time a patient is registered to the time the patient is shifted to a hospital bed or discharged. Increasing demand for quality emergency care has resulted in increased wait times due to demand and supply mismatch. It is perceived that longer LOS in the ED of critical patients leads to poor outcomes. Our goal was to study the impact of LOS in the ED on the patients who required critical care admissions. METHODS: This was a retrospective study conducted in the ED of a tertiary center. Data were collected using electronic health records (EHR) for patients admitted to the intensive care units (ICUs). Patient's LOS in ED was divided into 0-4, 4-8, 8-12, 12-24, and >24 hours. ED LOS was calculated from the registration time to the time patient was handed over in the ICU. Patients were divided into four categories (1-4) based on their criticality. LOS in ED, mortality, and total hospital LOS were analyzed in the study. RESULTS: Three thousand four hundred and twenty-nine patients were enrolled in the study. Mean age was 62.69 years (95% CI 62.11-63.26). A total of 42.09% (95% CI 40.5-43.8) were Category 1 patients. Overall mortality rate was 52.46% (95% CI 50.79-54.13). LOS of 48.15% (95% CI 46.54-49.88) patients in the ED was between 0 and 4 hours, 19.90% (95% CI 18.62-21.29) between 4 and 8 hours, 8.21% (95% CI 7.35-9.19) between 8 and 12 hours, 15.50% (95% CI 14.34-16.77) between 12 and 24 hours, and 8.13% (95% CI 7.27-9.10) >24 hours. Mortality for LOS of 0-4 hours was 51.30% (95% CI 48.89-53.70), 54.03% (95% CI 50.28-57.73) for 4-8 hours, 48.94% (95% CI 43.16-54.75) for 8-12 hours, 51.50% (95% CI 47.26-55.72) for 12-24 hours, and 60.57% (95% CI 54.73-66.13) for >24 hours. CONCLUSION: We concluded that the longer the critically ill patients are boarded in the ED, the higher is the chance for mortality. Processes should be implemented to ease the throughput from the ED. HOW TO CITE THIS ARTICLE: Verma A, Shishodia S, Jaiswal S, Sheikh WR, Haldar M, Vishen A, et al. Increased Length of Stay of Critically Ill Patients in the Emergency Department Associated with Higher In-hospital Mortality. Indian J Crit Care Med 2021;25(11):1221-1225.

Optimizing energetic cost of uncertainty in a driven system with and without feedback.

Many biological functions require dynamics to be necessarily driven out of equilibrium. In contrast, in various contexts, a nonequilibrium dynamics at fast timescales can be described by an effective equilibrium dynamics at a slower timescale. In this work, we study two different aspects: (i) the energy-efficiency tradeoff for a specific nonequilibrium linear dynamics of two variables with feedback and (ii) the cost of effective parameters in a coarse-grained theory as given by the "hidden" dissipation and entropy production rate in the effective equilibrium limit of the dynamics. To meaningfully discuss the tradeoff between energy consumption and the efficiency of the desired function, a one-to-one mapping between function(s) and energy input is required. The function considered in this work is the variance of one of the variables. We get a one-to-one mapping by considering the minimum variance obtained for a fixed entropy production rate and vice versa. We find that this minimum achievable variance is a monotonically decreasing function of the given entropy production rate. When there is a timescale separation, in the effective equilibrium limit, the cost of the effective potential and temperature is the associated "hidden" entropy production rate.

Reply to in Response to Guidewire Entrapped in the Right Ventricle.

How to cite this article: Verma A, Jaiswal S, Vishen A, Sheikh WR, Haldar M, Ahuja R, et al. Reply to in Response to Guidewire Entrapped in the Right Ventricle. Indian J Crit Care Med 2020;24(7):608.

Comparison of the time to successful endotracheal intubation using the Macintosh laryngoscope or KingVision video laryngoscope in the emergency department: A prospective observational study.

OBJECTIVE: Intubation is a skill that must be mastered by the emergency physician (EP). Today, we have a host of video laryngoscopes which have been developed to make intubations easier and faster. It may seem that in a busy emergency department (ED), a video laryngoscope (VL) in the hands of an EP would help him intubate patients faster compared to the traditional direct laryngoscope (DL). Our goal was to compare the time taken to successfully intubate patients coming in ED using King Vision VL (KVVL) and DL. MATERIALS AND METHODS: This was a prospective observational study on patients coming to the ED requiring emergent intubation. They were allocated one to one alternatively into two groups - KVVL and DL. Accordingly, KVVL or DL intubations were carried out by the EPs. Time taken to intubate, first-pass success, and crossover between laryngoscopes were recorded. RESULTS: A total of 350 patients were enrolled in the study. Overall, mean time to intubate patients using the DL was 15.85 s (95% confidence interval [CI] 14.05-17.65), while the meantime with KVVL was 13.75 s (95% CI 12.32-15.18) (P = 0.084). The overall first-pass success rates with DL and KVVL were 89.94% and 85.16%, respectively (P = 0.076). A total of 7.43% (95% CI 5.12-10.66) patients had crossover between laryngoscopes. CONCLUSION: We found the KVVL to have a similar performance to the DL in terms of time for intubations and ease in difficult airways. We consider the KVVL a useful device for EDs to equip themselves with.

Guidewire Entrapped in the Right Ventricle: A Rare Complication of Hemodialysis Catheter Insertion.

How to cite this article: Verma A, Chitransh V, Jaiswal S, Vishen A, Sheikh WR, Haldar M, et al. Guidewire Entrapped in the Right Ventricle: A Rare Complication of Hemodialysis Catheter Insertion. Indian J Crit Care Med 2020;24(1):80-81.

Ketamine Use allows Noninvasive Ventilation in Distressed Patients with Acute Decompensated Heart Failure.

Acute decompensated heart failure (ADHF) is responsible for a heavy clinical load on busy emergency departments (EDs) across the globe and especially in India. ADHF patients may present with severe respiratory distress, dyspnea, hypoxia, and high and low blood pressures. Managing the airway of such patients can at times be challenging. Nasal cannulae, face mask, and noninvasive positive pressure ventilation (NIPPV) are the cornerstones of providing oxygenation and ventilation to such patients while some extreme cases may require endotracheal intubation and mechanical ventilation. An elderly female in severe respiratory distress and altered sensorium presented to our ED and had to be administered ketamine to facilitate proper NIPPV and avoid mechanical ventilation. She was weaned off the NIPPV in the ED itself over the next four hours. There are some case reports of using ketamine for NIPPV in asthma exacerbations, but none for the use in ADHF. Avoiding invasive mechanical ventilation via endotracheal intubation should be a constant goal and the last resort. How to cite this article: Verma A, Snehy A, et al. Ketamine Use Allows Noninvasive Ventilation in Distressed Patients with Acute Decompensated Heart Failure. Indian J Crit Care Med 2019;23(4): 191-192.

Breakdown of effective temperature, power law interactions, and self-propulsion in a momentum-conserving active fluid.

The simplest extensions of single-particle dynamics in a momentum-conserving active fluid-an active suspension of two colloidal particles or a single particle confined by a wall-exhibit strong departures from Boltzmann behavior, resulting in either a breakdown of an effective temperature description or a steady state with nonzero-entropy production rate. This is a consequence of hydrodynamic interactions that introduce multiplicative noise in the stochastic description of particle positions. This results in fluctuation-induced interactions that depend on distance as a power law. We find that the dynamics of activated colloids in a passive fluid, with stochastic forcing localized on the particle, is different from that of passive colloids in an active fluctuating fluid.

Mechanochemical feedback control of dynamin independent endocytosis modulates membrane tension in adherent cells.

Plasma membrane tension regulates many key cellular processes. It is modulated by, and can modulate, membrane trafficking. However, the cellular pathway(s) involved in this interplay is poorly understood. Here we find that, among a number of endocytic processes operating simultaneously at the cell surface, a dynamin independent pathway, the CLIC/GEEC (CG) pathway, is rapidly and specifically upregulated upon a sudden reduction of tension. Moreover, inhibition (activation) of the CG pathway results in lower (higher) membrane tension. However, alteration in membrane tension does not directly modulate CG endocytosis. This requires vinculin, a mechano-transducer recruited to focal adhesion in adherent cells. Vinculin acts by controlling the levels of a key regulator of the CG pathway, GBF1, at the plasma membrane. Thus, the CG pathway directly regulates membrane tension and is in turn controlled via a mechano-chemical feedback inhibition, potentially leading to homeostatic regulation of membrane tension in adherent cells.

Soft inclusion in a confined fluctuating active gel.

We study stochastic dynamics of a point and extended inclusion within a one-dimensional confined active viscoelastic gel. We show that the dynamics of a point inclusion can be described by a Langevin equation with a confining potential and multiplicative noise. Using a systematic adiabatic elimination over the fast variables, we arrive at an overdamped equation with a proper definition of the multiplicative noise. To highlight various features and to appeal to different biological contexts, we treat the inclusion in turn as a rigid extended element, an elastic element, and a viscoelastic (Kelvin-Voigt) element. The dynamics for the shape and position of the extended inclusion can be described by coupled Langevin equations. Deriving exact expressions for the corresponding steady-state probability distributions, we find that the active noise induces an attraction to the edges of the confining domain. In the presence of a competing centering force, we find that the shape of the probability distribution exhibits a sharp transition upon varying the amplitude of the active noise. Our results could help understanding the positioning and deformability of biological inclusions, e.g., organelles in cells, or nucleus and cells within tissues.