Glioma nanotherapy: Unleashing the synergy of dual-loaded DIM and TMZ.

Glioblastoma multiforme (GBM) is a highly aggressive form of primary brain tumor in adults, which unfortunately has an abysmal prognosis and poor survival rates. The reason behind the poor success rate of several FDA-approved drug is mainly attributed to insufficient drug distribution to the tumor site across the blood-brain barrier (BBB) and induction of resistance. In this study, we have developed a novel nanotherapeutic approach to achieve our goal. PLGA-based nanoencapsulation of both Temozolomide (TMZ) and EGFR inhibitor 3,3'-diindoyl methane (DIM) in a combinatorial approach enhances the delivery of them together. Their synergistic mode of actions, significantly enhances the cytotoxic effect of TMZ in vitro and in vivo. Moreover, the dual-loaded nanoformulation works more efficiently on DNA damage and apoptosis, resulting in a several-fold reduction in tumor burden in vivo, systemic drug toxicity, and increased survival. These findings suggest the preclinical potential of this new treatment strategy.

Easily injectable gelatin-nonanal hydrogel for endoscopic resectioning of gastrointestinal polyps.

The use of submucosal injection is crucial for satisfactory submucosal elevation in the early resection of flat polyps originating from the gastrointestinal tract (GIT). Injectable hydrogels derived from natural polypeptides are attractive candidates due to their excellent biocompatibility and easy gelation properties. However, most of the reported hydrogels are not the class of catheter delivery materials due to quick gelation, high inherent viscosity, and injection clogging. This study presents a novel injectable shear-thinning hydrogel platform of small molecules (nonanal) modified gelatin polymer, which offers a promising submucosal injection for effective removal of polyps from GIT. Physicochemical characterizations of hydrogel demonstrate the suitable features as an effective submucosal injection, including shear thinning property, self-assembly, methylene blue dye encapsulation, flow behavior, stability, syringeability (18 G, 21 G, and 24 G needles) and fibrous morphology. Ex vivo investigations of developed submucosal formulation on goat intestines demonstrate the enhanced visibility of cushions and the ability to produce stable, long-lasting cushions of about 8.07 mm up to ∼60 min of submucosal injection. The rapid blood clotting behavior of hydrogel was observed in about 120 s without compromising hemocompatibility with the hemolysis of about 3.77 % only. In vitro biocompatibility of the hydrogel was also verified using the HepG2 and nHDF cells. In vivo study depicts desirable biocompatibility, a non-toxic organ profile, and optimal cushion height in mice models. Studies established the foundation of novel submucosal fluid to improve the therapeutic outcomes of early resection for gastrointestinal polyps.

GBM immunotherapy: Exploring molecular and clinical frontiers.

GBM is the most common, aggressive, and intracranial primary brain tumor; it originates from the glial progenitor cells, has poor overall survival (OS), and has limited treatment options. In this decade, GBM immunotherapy is in trend and preferred over several conventional therapies, due to their better patient survival outcome. This review explores the clinical trials of several immunotherapeutic approaches (immune checkpoint blockers (ICBs), CAR T-cell therapy, cancer vaccines, and adoptive cell therapy) with their efficacy and safety. Despite significant progress, several challenges (viz., immunosuppressive microenvironment, heterogeneity, and blood-brain barrier (BBB)) were experienced that hamper their immunotherapeutic potential. Furthermore, these challenges were clinically studied to be resolved by multiple combinatorial approaches, discussed in the later part of the review. Thus, this review suggests the clinical use and potential of immunotherapy in GBM and provides the holistic recent knowledge and future perspectives.

E3 ubiquitin ligases and deubiquitinases in colorectal cancer: Emerging molecular insights and therapeutic opportunities.

Colorectal cancer (CRC) presents ongoing challenges due to limited treatment effectiveness and a discouraging prognosis, underscoring the need for ground-breaking therapeutic approaches. This review delves into the pivotal role of E3 ubiquitin ligases and deubiquitinases (DUBs), underscoring their role as crucial regulators for tumor suppression and oncogenesis in CRC. We spotlight the diverse impact of E3 ligases and DUBs on CRC's biological processes and their remarkable versatility. We closely examine their specific influence on vital signaling pathways, particularly Wnt/ß-catenin and NF-κB. Understanding these regulatory mechanisms is crucial for unravelling the complexities of CRC progression. Importantly, we explore the untapped potential of E3 ligases and DUBs as novel CRC treatment targets, discussing aspects that may guide more effective therapeutic strategies. In conclusion, our concise review illuminates the E3 ubiquitin ligases and deubiquitinases pivotal role in CRC, offering insights to inspire innovative approaches for transforming the treatment landscape in CRC.

Comparative Profiles of the WATCHMAN™ and Amplatzer™ Cardiac Plug/Amplatzer™ Amulet™ Devices for Left Atrial Appendage Closure in Non-valvular Atrial Fibrillation: A Comprehensive Systematic Review and Meta-analysis.

Atrial fibrillation (AF) is a prevalent cardiac arrhythmia marked by irregular and frequent tachycardic rhythms in the atria, affecting 1%-2% of the general population. The WATCHMAN™ device from Boston Scientific (Marlborough, MA, USA) and the Amplatzer™ Amulet™ device from Abbott (Chicago, IL, USA) are two devices used globally for left atrial appendage closure (LAAC) in non-valvular AF. A systematic search was conducted in PubMed, the Cochrane Library, and Elsevier's ScienceDirect literature databases to identify studies comparing the WATCHMAN™ procedure with Amulet™ device implantation for LAAC in patients with AF. The analyses were conducted using the random-effects model. A total of 20 studies were identified, with 18 falling into the category of observational studies and 2 being randomized controlled trials. A total of 6310 participants were included in this meta-analysis, with 3198 individuals (50.68%) assigned to the WATCHMAN™ procedure group and 3112 individuals (49.32%) allocated to the Amplatzer™ Cardiac Plug (ACP) group. The analysis revealed a higher risk of stroke associated with the WATCHMAN™ technique (relative risk [RR], 1.14), albeit without statistical significance. Conversely, the WATCHMAN™ approach led to a significantly lower risk of cardiac death (RR, 0.44; P = .04). Notably, the risks of all-cause mortality (RR, 0.89; 95% confidence interval [CI], 0.73-1.08; I 2 = 0%; P = .25) and major bleeding (RR, 0.93; 95% CI, 0.65-1.33; I 2 = 31%; P = .70) were clinically reduced with the WATCHMAN™ procedure, although statistical significance was not achieved. Compared to Amulet™ device implantation, WATCHMAN™ device implantation decreased the risk of cardiac mortality, while the risks of stroke, systemic embolism, all-cause mortality, and major bleeding were not statistically significant.

Reversible kink instability drives ultrafast jumping in nematodes and soft robots.

Entomopathogenic nematodes (EPNs) exhibit a bending-elastic instability, or kink, before becoming airborne, a feature hypothesized but not proven to enhance jumping performance. Here, we provide the evidence that this kink is crucial for improving launch performance. We demonstrate that EPNs actively modulate their aspect ratio, forming a liquid-latched closed loop over a slow timescale O (1 s), then rapidly open it O (10 µs), achieving heights of 20 body lengths (BL) and generating ∼ 10 4 W/Kg of power. Using jumping nematodes, a bio-inspired Soft Jumping Model (SoftJM), and computational simulations, we explore the mechanisms and implications of this kink. EPNs control their takeoff direction by adjusting their head position and center of mass, a mechanism verified through phase maps of jump directions in simulations and SoftJM experiments. Our findings reveal that the reversible kink instability at the point of highest curvature on the ventral side enhances energy storage using the nematode's limited muscular force. We investigated the impact of aspect ratio on kink instability and jumping performance using SoftJM, and quantified EPN cuticle stiffness with AFM, comparing it with C. elegans . This led to a stiffness-modified SoftJM design with a carbon fiber backbone, achieving jumps of ∼25 BL. Our study reveals how harnessing kink instabilities, a typical failure mode, enables bidirectional jumps in soft robots on complex substrates like sand, offering a novel approach for designing limbless robots for controlled jumping, locomotion, and even planetary exploration.

A paper-based point-of-care device for the detection of cysteine using gold nanoparticles from whole blood.

We present a colorimetric probe based on polyvinylpyrrolidone-capped gold nanoparticles (PVP-AuNPs) that is sensitive and selective for cysteine (Cys). A microfluidic paper-based analytical device (µ-PAD) with embedded dried PVP-AuNPs at the polyethersulfone (PES) paper surface is used for Cys detection. When thiol molecules attach to PVP-AuNPs in the presence of Cys, they clump together, and this causes the solution's color to shift from red to blue within 5 minutes. The device is capable of detecting Cys levels between 1.0 µM and 50.0 µM with a limit of detection (LOD) of 0.2 µM under optimized conditions. The stability of the µ-PAD was tested for 100 days, demonstrating re-dispersibility to detect Cys levels in blood. Dried PVP-AuNP-µPADs were integrated with blood plasma separation modules for point-of-care (POC) Cys detection. Consequently, the device shows potential as a self-sustaining, quantification platform with a recovery percentage ranging from 98.44 to 111.9 in clinical samples.

Composition and interaction of maternal microbiota with immune mediators during pregnancy and their outcome: A narrative review.

The connection between maternal microbiota and infant health has been greatly garnered interest for therapeutic purposes. The early resident microbiota perpetually exhibits much more flexibility as compared to that of the adults, and therefore, constant need of understanding the infant as well as maternal microbiota and their implications however has increased. In this review, we focus mainly on the diversity of overall maternal microbiota including the gut, vaginal, colostrum microbiota and how inflammatory markers fluctuate throughout the normal pregnancy as well in pregnancy with complications. The maternal body undergoes a cascade of physiological changes including hormonal, immunological and metabolic events to support the fetal development. These changes at the time of pregnancy have been correlated with alteration in the composition and diversity of maternal microbiota. Along with alteration in microbiome, the levels of circulatory cytokines fluctuate by complex network of inflammation, in order to prevent the fetal allograft throughout the pregnancy. The dynamic relationship of gut microbiota with the host and its immune system allows one to have greater insights of their role in pregnancy and newborn's health. Emerging evidence suggests that the vertical transmission of bacterial community from mother to newborn may begin in-utero which contributes in developing the immune system and infant gut microbiota.

Head-to-head comparison of [18F]-Flortaucipir, [18F]-MK-6240 and [18F]-PI-2620 postmortem binding across the spectrum of neurodegenerative diseases.

We and others have shown that [18F]-Flortaucipir, the most validated tau PET tracer thus far, binds with strong affinity to tau aggregates in Alzheimer's (AD) but has relatively low affinity for tau aggregates in non-AD tauopathies and exhibits off-target binding to neuromelanin- and melanin-containing cells, and to hemorrhages. Several second-generation tau tracers have been subsequently developed. [18F]-MK-6240 and [18F]-PI-2620 are the two that have garnered most attention. Our recent data indicated that the binding pattern of [18F]-MK-6240 closely parallels that of [18F]-Flortaucipir. The present study aimed at the direct comparison of the autoradiographic binding properties and off-target profile of [18F]-Flortaucipir, [18F]-MK-6240 and [18F]-PI-2620 in human tissue specimens, and their potential binding to monoamine oxidases (MAO). Phosphor-screen and high resolution autoradiographic patterns of the three tracers were studied in the same postmortem tissue material from AD and non-AD tauopathies, cerebral amyloid angiopathy, synucleopathies, transactive response DNA-binding protein 43 (TDP-43)-frontotemporal lobe degeneration and controls. Our results show that the three tracers show nearly identical autoradiographic binding profiles. They all strongly bind to neurofibrillary tangles in AD but do not seem to bind to a significant extent to tau aggregates in non-AD tauopathies pointing to their limited utility for the in vivo detection of non-AD tau lesions. None of them binds to lesions containing ß-amyloid, α-synuclein or TDP-43 but they all show strong off-target binding to neuromelanin and melanin-containing cells, as well as weaker binding to areas of hemorrhage. The autoradiographic binding signals of the three tracers are only weakly displaced by competing concentrations of selective MAO-B inhibitor deprenyl but not by MAO-A inhibitor clorgyline suggesting that MAO enzymes do not appear to be a significant binding target of any of them. These findings provide relevant insights for the correct interpretation of the in vivo behavior of these three tau PET tracers.

Air-to-land transitions: from wingless animals and plant seeds to shuttlecocks and bio-inspired robots.

Recent observations of wingless animals, including jumping nematodes, springtails, insects, and wingless vertebrates like geckos, snakes, and salamanders, have shown that their adaptations and body morphing are essential for rapid self-righting and controlled landing. These skills can reduce the risk of physical damage during collision, minimize recoil during landing, and allow for a quick escape response to minimize predation risk. The size, mass distribution, and speed of an animal determine its self-righting method, with larger animals depending on the conservation of angular momentum and smaller animals primarily using aerodynamic forces. Many animals falling through the air, from nematodes to salamanders, adopt a skydiving posture while descending. Similarly, plant seeds such as dandelions and samaras are able to turn upright in mid-air using aerodynamic forces and produce high decelerations. These aerial capabilities allow for a wide dispersal range, low-impact collisions, and effective landing and settling. Recently, small robots that can right themselves for controlled landings have been designed based on principles of aerial maneuvering in animals. Further research into the effects of unsteady flows on self-righting and landing in small arthropods, particularly those exhibiting explosive catapulting, could reveal how morphological features, flow dynamics, and physical mechanisms contribute to effective mid-air control. More broadly, studying apterygote (wingless insects) landing could also provide insight into the origin of insect flight. These research efforts have the potential to lead to the bio-inspired design of aerial micro-vehicles, sports projectiles, parachutes, and impulsive robots that can land upright in unsteady flow conditions.

Targeting PD-1/PD-L1 in cancer immunotherapy: An effective strategy for treatment of triple-negative breast cancer (TNBC) patients.

Maintaining the balance between eliciting immune responses against foreign proteins and tolerating self-proteins is crucial for maintenance of homeostasis. The functions of programmed death protein 1 (PD-1) and its ligand programmed death ligand 1 (PD-L1) are to inhibit immune responses so that over-reacting immune cells does not cause any damage to its own body cells. However, cancer cells hijack this mechanism to attenuate immune cells functions and create an immunosuppressive environment that fuel their continuous growth and proliferation. Over the past few years' rapid development in cancer immunotherapy has opened a new avenue in cancer treatment. Blockade of PD-1 and PD-L1 has become a potential strategy that rescue the functions of immune cells to fight against cancer with high efficacy. Initially, immune checkpoint monotherapies were not very successful, making breast cancer less immunogenic. Although, recent reports support the presence of tumor infiltrating lymphocytes (TILs) in breast cancer that make it favorable for PD-1/PD-L1 mediated immunotherapy, which is effective in PD-L1 positive patients. Recently, anti-PD-1 (pembrolizumab) and anti-PD-L1 (atezolizumab) gets FDA approval for breast cancer treatment and make PD-1/PD-L1 immunotherapy is meaningful for further research. Likewise, this article gathered understanding of PD-1 and PD-L1 in recent years, their signaling networks, interaction with other molecules, regulations of their expressions and functions in both normal and tumor tissue microenvironments are crucial to find and design therapeutic agents that block this pathway and improve the treatment efficacy. Additionally, authors collected and highlighted most of the important clinical trial reports on monotherapy and combination therapy.

COVID-19 therapeutics: Clinical application of repurposed drugs and futuristic strategies for target-based drug discovery.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes the complicated disease COVID-19. Clinicians are continuously facing huge problems in the treatment of patients, as COVID-19-specific drugs are not available, hence the principle of drug repurposing serves as a one-and-only hope. Globally, the repurposing of many drugs is underway; few of them are already approved by the regulatory bodies for their clinical use and most of them are in different phases of clinical trials. Here in this review, our main aim is to discuss in detail the up-to-date information on the target-based pharmacological classification of repurposed drugs, the potential mechanism of actions, and the current clinical trial status of various drugs which are under repurposing since early 2020. At last, we briefly proposed the probable pharmacological and therapeutic drug targets that may be preferred as a futuristic drug discovery approach in the development of effective medicines.

Prevalence and etiology of Helicobacter pylori infection in dyspepsia patients: a hospital-based cross-sectional study.

Helicobacter pylori infection is seropositive in ~50% of people globally. Therefore, this study was conducted to evaluate its prevalence in dyspepsia patients. Methods: A cross-sectional study was conducted at Jinnah Postgraduate Medical Centre (JPMC) from January to June 2022 to find out the prevalence and risk factors of H. pylori in dyspepsia patients. A prevalidated questionnaire was used to collect the data from 180 patients. This study adheres to the principles outlined in the Helsinki Declaration. The χ 2-test was applied, and the odds ratio and 95% CI were calculated to find the association of H. pylori with the risk factors. Results: A total of 180 patients were enrolled in this study, of whom, 73 (40.6%) patients were male and 107 (59.4%) were female. In seropositive H. pylori patients, 80 (60.6%) patients had nausea or vomiting, 110 (83.3%) patients were found to have flatulence, 128 (97.7%) patients were experiencing frequent burping, and 114 (86.4%) patients were having epigastric pain. The household member greater than 4, smoking, rural area residence, NSAIDs consumption, BMI greater than 25, O+ blood group, and Rhesus positive status were significantly associated with H. pylori with a P value of less than 0.05. Conclusion: This study concludes that the prevalence of H. pylori in our population is high, and the risk factors identified are lower class, BMI greater than 25, smoking, O+ blood group, NSAID consumption, rural area residence, household member greater than 4, Rhesus positive status, and the symptoms of nausea or vomiting, frequent burping, epigastric pain, and flatulence. Patients with an increased number of risk factors should be taken into consideration for an appropriate checkup.

COVID-19: Clinical status of vaccine development to date.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-induced COVID-19 is a complicated disease. Clinicians are continuously facing difficulties to treat infected patients using the principle of repurposing of drugs as no specific drugs are available to treat COVID-19. To minimize the severity and mortality, global vaccination is the only hope as a potential preventive measure. After a year-long global research and clinical struggle, 165 vaccine candidates have been developed and some are currently still in the pipeline. A total of 28 candidate vaccines have been approved for use and the remainder are in different phases of clinical trials. In this comprehensive report, the authors aim to demonstrate, classify and provide up-to-date clinical trial status of all the vaccines discovered to date and specifically focus on the approved candidates. Finally, the authors specifically focused on the vaccination of different types of medically distinct populations.

Insulin Resistance and Coronary Artery Disease: Untangling the Web of Endocrine-Cardiac Connections.

The relationship between insulin resistance and coronary artery disease (CAD) is a crucial study area in understanding the complex connection between metabolic dysregulation and cardiovascular morbidity. This scholarly investigation examines the intricate relationship between insulin resistance, a key characteristic of metabolic syndrome, and CAD development. The goal is to understand the detailed molecular and physiological connections that underlie the dangerous connection between the endocrine and cardiac systems. The recognition of insulin resistance as a key player in cardiovascular disease highlights the need to study the complex relationships between insulin signaling pathways and the development of atherosclerosis. This research analyzes the molecular processes by which insulin resistance leads to disruptions in lipid metabolism, inflammatory reactions, and malfunction of the blood vessel's inner lining. These processes create an environment that promotes the development and advancement of CAD. As we begin this scientific exploration, it becomes clear that insulin resistance acts as a metabolic indicator and a potent mediator of endothelial dysfunction, oxidative stress, and systemic inflammation. The complex interaction between insulin-sensitive tissues and the vascular endothelium plays a crucial role in defining the pathophysiological landscape of CAD. Furthermore, this discussion highlights the mutual interaction between the endocrine and cardiac systems, where CAD produced by myocardial ischemia worsens insulin resistance through complex molecular pathways. Discovering new therapeutic targets that disrupt the harmful cycle between insulin resistance and the development of CAD shows potential for creating specific therapies to reduce cardiovascular risk in people with insulin resistance. This study aims to clarify the complexities of the connection between the endocrine system and the heart, establishing the basis for a thorough comprehension of how insulin resistance contributes to the development and advancement of CAD.

Impact of recent climate change on corn, rice, and wheat in southeastern USA.

Climate change and its impact on agriculture productivity vary among crops and regions. The southeastern United States (SE-US) is agro-ecologically diversified, economically dependent on agriculture, and mostly overlooked by agroclimatic researchers. The objective of this study was to compute the effect of climatic variables; daily maximum temperature (Tmax), daily minimum temperature (Tmin), and rainfall on the yield of major cereal crops i.e., corn (Zea mays L.), rice (Oryza sativa L.), and wheat (Triticum aestivum L.) in SE-US. A fixed-effect model (panel data approach) was used by applying the production function on panel data from 1980 to 2020 from 11 SE-US states. An asymmetrical warming pattern was observed, where nocturnal warming was 105.90%, 106.30%, and 32.14%, higher than the diurnal warming during corn, rice, and wheat growing seasons, respectively. Additionally, a shift in rainfall was noticed ranging from 19.2 to 37.2 mm over different growing seasons. Rainfall significantly reduced wheat yield, while, it had no effect on corn and rice yields. The Tmax and Tmin had no significant effect on wheat yield. A 1 °C rise in Tmax significantly decreased corn (- 34%) and rice (- 8.30%) yield which was offset by a 1 °C increase in Tmin increasing corn (47%) and rice (22.40%) yield. Conclusively, overall temperature change of 1 °C in the SE-US significantly improved corn yield by 13%, rice yield by 14.10%, and had no effect on wheat yield.

Chaperone-assisted E3 ligase CHIP: A double agent in cancer.

The carboxy-terminus of Hsp70-interacting protein (CHIP) is a ubiquitin ligase and co-chaperone belonging to Ubox family that plays a crucial role in the maintenance of cellular homeostasis by switching the equilibrium of the folding-refolding mechanism towards the proteasomal or lysosomal degradation pathway. It links molecular chaperones viz. HSC70, HSP70 and HSP90 with ubiquitin proteasome system (UPS), acting as a quality control system. CHIP contains charged domain in between N-terminal tetratricopeptide repeat (TPR) and C-terminal Ubox domain. TPR domain interacts with the aberrant client proteins via chaperones while Ubox domain facilitates the ubiquitin transfer to the client proteins for ubiquitination. Thus, CHIP is a classic molecule that executes ubiquitination for degradation of client proteins. Further, CHIP has been found to be indulged in cellular differentiation, proliferation, metastasis and tumorigenesis. Additionally, CHIP can play its dual role as a tumor suppressor as well as an oncogene in numerous malignancies, thus acting as a double agent. Here, in this review, we have reported almost all substrates of CHIP established till date and classified them according to the hallmarks of cancer. In addition, we discussed about its architectural alignment, tissue specific expression, sub-cellular localization, folding-refolding mechanisms of client proteins, E4 ligase activity, normal physiological roles, as well as involvement in various diseases and tumor biology. Further, we aim to discuss its importance in HSP90 inhibitors mediated cancer therapy. Thus, this report concludes that CHIP may be a promising and worthy drug target towards pharmaceutical industry for drug development.

Long-Term Symptoms of COVID-19: One-Year Follow-Up Study.

INTRODUCTION:  Persistent and prolonged symptoms, termed as long COVID (coronavirus disease), have been reported in several patients who recovered from the acute phase at different intervals. However, there has been largely unclear data regarding the full range of long-term sequelae of coronavirus disease 2019 (COVID-19) patients. This study aims to evaluate the prevalence of long COVID syndrome. METHODS: A long-term research was conducted in the COVID-19 unit of a tertiary care hospital in Pakistan from July 2020 to December 2021 in which 2,000 patients who had recovered from COVID-19 and had been discharged were included in the study. Symptoms were noted at the time of discharge and at follow-up after 12 months. Data were analyzed using Statistical Package for the Social Sciences (SPSS) v. 22.0 (IBM Corporation, Armonk, New York, United States). RESULTS: The mean age of the participants was 43 ± 10 years, 801 (53.8%) males and 688 (46.2%) females. At the time of discharge, the most common symptom was fatigue (26.93%), followed by dyspnea (20.34%) and muscle pain (8.86%). The most common symptom on follow-up was fatigue (6.78%). CONCLUSION: We strongly emphasize discussing and exploring further knowledge on the post-infection syndrome, with an aim to bring healthcare professionals' attention to the importance of handling COVID patients, their counseling, warning for alarming signs, and a long-term follow-up with necessary investigations and treatment.

Helmet NIV in Acute Hypoxemic Respiratory Failure due to COVID-19: Change in PaO2/FiO2 Ratio a Predictor of Success.

In acute respiratory failure due to severe coronavirus disease 2019 (COVID-19) pneumonia, mechanical ventilation remains challenging and may result in high mortality. The use of noninvasive ventilation (NIV) may delay required invasive ventilation, increase adverse outcomes, and have a potential aerosol risk to caregivers. Data of 30 patients were collected from patient files and analyzed. Twenty-one (70%) patients were weaned successfully after helmet-NIV support (NIV success group), and invasive mechanical ventilation was required in 9 (30%) patients (NIV failure group) of which 8 (26.7%) patients died. In NIV success vs failure patients, the mean baseline PaO2/FiO2 ratio (PFR) (147.2 ± 57.9 vs 156.8 ± 59.0 mm Hg; p = 0.683) and PFR before initiation of helmet (132.3 ± 46.9 vs 121.6 ± 32.7 mm Hg; p = 0.541) were comparable. The NIV success group demonstrated a progressive improvement in PFR in comparison with the failure group at 2 hours (158.8 ± 56.1 vs 118.7 ± 40.7 mm Hg; p = 0.063) and 24 hours (PFR-24) (204.4 ± 94.3 vs 121.3 ± 32.6; p = 0.016). As predictor variables, PFR-24 and change (delta) in PFR at 24 hours from baseline or helmet initiation (dPFR-24) were significantly associated with NIV success in univariate analysis but similar significance could not be reflected in multivariate analysis perhaps due to a small sample size of the study. The PFR-24 cutoff of 161 mm Hg and dPFR-24 cutoff of -1.44 mm Hg discriminate NIV success and failure groups with the area under curve (confidence interval) of 0.78 (0.62-0.95); p = 0.015 and 0.74 (0.55-0.93); p = 0.039, respectively. Helmet interface NIV may be a safe and effective tool for the management of patients with severe COVID-19 pneumonia with acute respiratory failure. More studies are needed to further evaluate the role of helmet NIV especially in patients with initial PFR <150 mm Hg to define PFR/dPFR cutoff at the earliest time point for prediction of helmet-NIV success. How to cite this article Jha OK, Kumar S, Mehra S, Sircar M, Gupta R. Helmet NIV in Acute Hypoxemic Respiratory Failure due to COVID-19: Change in PaO2/FiO2 Ratio a Predictor of Success. Indian J Crit Care Med 2021;25(10):1137-1146.