Microbial exposure during early human development primes fetal immune cells.

The human fetal immune system begins to develop early during gestation; however, factors responsible for fetal immune-priming remain elusive. We explored potential exposure to microbial agents in utero and their contribution toward activation of memory T cells in fetal tissues. We profiled microbes across fetal organs using 16S rRNA gene sequencing and detected low but consistent microbial signal in fetal gut, skin, placenta, and lungs in the 2nd trimester of gestation. We identified several live bacterial strains including Staphylococcus and Lactobacillus in fetal tissues, which induced in vitro activation of memory T cells in fetal mesenteric lymph node, supporting the role of microbial exposure in fetal immune-priming. Finally, using SEM and RNA-ISH, we visualized discrete localization of bacteria-like structures and eubacterial-RNA within 14th weeks fetal gut lumen. These findings indicate selective presence of live microbes in fetal organs during the 2nd trimester of gestation and have broader implications toward the establishment of immune competency and priming before birth.

Onco-fetal Reprogramming of Endothelial Cells Drives Immunosuppressive Macrophages in Hepatocellular Carcinoma.

We employed scRNA sequencing to extensively characterize the cellular landscape of human liver from development to disease. Analysis of ∼212,000 cells representing human fetal, hepatocellular carcinoma (HCC), and mouse liver revealed remarkable fetal-like reprogramming of the tumor microenvironment. Specifically, the HCC ecosystem displayed features reminiscent of fetal development, including re-emergence of fetal-associated endothelial cells (PLVAP/VEGFR2) and fetal-like (FOLR2) tumor-associated macrophages. In a cross-species comparative analysis, we discovered remarkable similarity between mouse embryonic, fetal-liver, and tumor macrophages. Spatial transcriptomics further revealed a shared onco-fetal ecosystem between fetal liver and HCC. Furthermore, gene regulatory analysis, spatial transcriptomics, and in vitro functional assays implicated VEGF and NOTCH signaling in maintaining onco-fetal ecosystem. Taken together, we report a shared immunosuppressive onco-fetal ecosystem in fetal liver and HCC. Our results unravel a previously unexplored onco-fetal reprogramming of the tumor ecosystem, provide novel targets for therapeutic interventions in HCC, and open avenues for identifying similar paradigms in other cancers and disease.

Cross-tissue single-cell landscape of human monocytes and macrophages in health and disease.

Mononuclear phagocytes (MNPs) encompass dendritic cells, monocytes, and macrophages (MoMac), which exhibit antimicrobial, homeostatic, and immunoregulatory functions. We integrated 178,651 MNPs from 13 tissues across 41 datasets to generate a MNP single-cell RNA compendium (MNP-VERSE), a publicly available tool to map MNPs and define conserved gene signatures of MNP populations. Next, we generated a MoMac-focused compendium that revealed an array of specialized cell subsets widely distributed across multiple tissues. Specific pathological forms were expanded in cancer and inflammation. All neoplastic tissues contained conserved tumor-associated macrophage populations. In particular, we focused on IL4I1+CD274(PD-L1)+IDO1+ macrophages, which accumulated in the tumor periphery in a T cell-dependent manner via interferon-γ (IFN-γ) and CD40/CD40L-induced maturation from IFN-primed monocytes. IL4I1_Macs exhibited immunosuppressive characteristics through tryptophan degradation and promoted the entry of regulatory T cell into tumors. This integrated analysis provides a robust online-available platform for uniform annotation and dissection of specific macrophage functions in healthy and pathological states.

A subset of Kupffer cells regulates metabolism through the expression of CD36.

Tissue macrophages are immune cells whose phenotypes and functions are dictated by origin and niches. However, tissues are complex environments, and macrophage heterogeneity within the same organ has been overlooked so far. Here, we used high-dimensional approaches to characterize macrophage populations in the murine liver. We identified two distinct populations among embryonically derived Kupffer cells (KCs) sharing a core signature while differentially expressing numerous genes and proteins: a major CD206loESAM- population (KC1) and a minor CD206hiESAM+ population (KC2). KC2 expressed genes involved in metabolic processes, including fatty acid metabolism both in steady-state and in diet-induced obesity and hepatic steatosis. Functional characterization by depletion of KC2 or targeted silencing of the fatty acid transporter Cd36 highlighted a crucial contribution of KC2 in the liver oxidative stress associated with obesity. In summary, our study reveals that KCs are more heterogeneous than anticipated, notably describing a subpopulation wired with metabolic functions.

Advances in cellular and tissue-based imaging techniques for sarcoid granulomas.

Sarcoidosis embodies a complex inflammatory disorder spanning multiple systems, with its origin remaining elusive. It manifests as the infiltration of inflammatory cells that coalesce into distinctive noncaseous granulomas within afflicted organs. Unraveling this disease necessitates the utilization of cellular or tissue-based imaging methods to both visualize and characterize the biochemistry of these sarcoid granulomas. Although hematoxylin and eosin stain, standard in routine use alongside cytological stains have found utility in diagnosis within clinical contexts, special stains such as Masson's trichrome, reticulin, methenamine silver, and Ziehl-Neelsen provide additional varied perspectives of sarcoid granuloma imaging. Immunohistochemistry aids in pinpointing specific proteins and gene expressions further characterizing these granulomas. Finally, recent advances in spatial transcriptomics promise to divulge profound insights into their spatial orientation and three-dimensional (3-D) molecular mapping. This review focuses on a range of preexisting imaging methods employed for visualizing sarcoid granulomas at the cellular level while also exploring the potential of the latest cutting-edge approaches like spatial transcriptomics and matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI), with the overarching goal of shedding light on the trajectory of sarcoidosis research.

Lipoplexes' Structure, Preparation, and Role in Managing Different Diseases.

Lipid-based vectors are becoming promising alternatives to traditional therapies over the last 2 decades specially for managing life-threatening diseases like cancer. Cationic lipids are the most prevalent non-viral vectors utilized in gene delivery. The increasing number of clinical trials about lipoplex-based gene therapy demonstrates their potential as well-established technology that can provide robust gene transfection. In this regard, this review will summarize this important point. These vectors however have a modest transfection efficiency. This limitation can be partly addressed by using functional lipids that provide a plethora of options for investigating nucleic acid-lipid interactions as well as in vitro and in vivo nucleic acid delivery for biomedical applications. Despite their lower gene transfer efficiency, lipid-based vectors such as lipoplexes have several advantages over viral ones: they are less toxic and immunogenic, can be targeted, and are simple to produce on a large scale. Researchers are actively investigating the parameters that are essential for an effective lipoplex delivery method. These include factors that influence the structure, stability, internalization, and transfection of the lipoplex. Thorough understanding of the design principles will enable synthesis of customized lipoplex formulations for life-saving therapy.

Investigating the dynamic nature of landslide susceptibility in the Indian Himalayan region.

Landslide susceptibility zonation (LSZ) mapping is used to delineate areas prone to landslides and is critical for effective landslide hazard management. The existing methodologies for generating such maps tend to neglect the influence of dynamic environmental variables on landslide occurrences, which may lead to obsolete and erroneous estimates of landslide susceptibility (LS) for a concerned area. Although recent studies have started to report the effects of Land Use/ Land Cover (LULC) variation on LSZ mapping, variations in other dynamic variables like rainfall, soil moisture, and evapotranspiration apart from LULC may also influence slope stability in mountainous regions. The present study investigates the impact of variations in these four variables on the LS distribution, of a selected Indian Himalayan region between 2017 and 2021. Random Forest (RF) susceptibility models are utilized for evaluating the LS for the selected years and geospatial technologies are employed for LS change detection. The results indicate up to 19% variations in the spatial extent for some of the zones of the generated LSZ maps. The research findings of this study are crucial since they reveal the impact of dynamic behavior on LS, which has not been previously documented in the literature.

Comparison of Oxygen Delivery Devices in Postoperative Patients with Hypoxemia: An Open-labeled Randomized Controlled Study.

Background: Acute hypoxemic respiratory failure is among the more commonly occurring complications in postoperative patients. Supplemental oxygen and addressing the primary etiology form the basis of its treatment. Materials and methods: We conducted an open-labeled randomized control trial with 90 adult patients and compared three oxygen delivery vehicles (ODV), i.e., noninvasive ventilation (NIV), high-flow nasal cannula (HFNC), and venturi mask (VM) in postoperative hypoxemic patients. The primary outcome variable was a change in the P/F ratio after 2 hours of use of ODV. Results: It was observed that the change in P/F ratio after 2 hours was similar in all three ODV groups (p = 0.274). The mean values of the post-ODV P/F ratio were comparable with the pre-ODV P/F ratio in all three modalities. The P/F ratio after HFNC was 358.08 ± 117.95; after NIV was 357.60 ± 220.67; and after VM was 355.47 ± 101.90 (p = 0.997). Conclusion: Among HFNC, NIV, and VM, none of the devices proved superior to the other for use in postoperative hypoxemia. How to cite this article: Mishra S, Kothari N, Sharma A, Goyal S, Rathod D, Meshram T, et al. Comparison of Oxygen Delivery Devices in Postoperative Patients with Hypoxemia: An Open-labeled Randomized Controlled Study. Indian J Crit Care Med 2024;28(3):294-298.

Comparison of midpoint transverse process to pleura (MTP) block and erector spinae plane block (ESP) for postoperative analgesia in modified radical mastectomy patients: A double-blinded, randomized control trial.

Background and Aims: Modified radical mastectomy (MRM) is associated with moderate severity of postoperative pain. Besides intravenous (IV) analgesics, various nerve blocks are being described for pain relief of MRM patients. We compared erector spinae plane (ESP) block with midpoint transverse process to pleura (MTP) block in these patients for postoperative analgesia. Material and Methods: After receiving ethical committee approval from the institutional ethics committee (AIIMS, Jodhpur) and written informed consent from study participants, 66 patients who were assigned American Society of Anesthesiologists (ASA) physical status I and II, aged 18-75 years, and were scheduled to undergo MRM were enrolled and randomly allocated into two groups. Unilateral block was given before surgery at T3 or T4 level and with 15 ml of 0.5% ropivacaine in both the groups. Infusion of 0.5% ropivacaine (Neon laboratories limited, Mumbai, India) and 0.2% ropivacaine at a rate of 5 ml/h was maintained intraoperatively and postoperatively, respectively. Pain was assessed using the Visual Analogue Scale (VAS) for the next 24 hours. The total number of patients needing rescue analgesia, the total amount of rescue analgesics consumed in the next 24 hours, and patient satisfaction score were also compared between groups. Results: Demographics and baseline vitals were comparable in the groups. On comparing VAS scores in both the groups during rest and movement at different time intervals, there was no difference in pain scores during the initial two hours. From the third hour, there was a statistically significant difference (P < 0.001) in pain VAS scores in both groups. The ESP group had lower VAS scores compared to the MTP group when followed for the next 24 hours. There was a statistically significant difference in patient satisfaction. Conclusion: ESP block is more efficacious when compared to MTP block for postoperative analgesia in MRM patients.

Immunosuppressive mechanisms of oncofetal reprogramming in the tumor microenvironment: implications in immunotherapy response.

Both fetal and tumor tissue microenvironments display immunosuppressive features characterized by the presence of specific immunomodulatory stromal and immune cell populations. Recently, we discovered shared microenvironments between hepatocellular carcinoma (HCC) and fetal tissues and described this phenomenon as an oncofetal ecosystem. This ecosystem includes fetal-like immune (macrophage) and stromal (endothelial) cells within the tumor microenvironment (TME). This discovery highlights reciprocal interactions between fetal-like macrophages and T cells which result in the orchestration of an immunosuppressive TME. Importantly, VEGF-A protein expression by tumor cells and fetal-like macrophages plays an important role in oncofetal reprogramming of the TME in HCCs. Interestingly, recent clinical data indicate that blocking VEGF-A or CTLA4 alongside PD-L1 is effective in treating advanced HCC. Consequently, some immunotherapies may target and rely on oncofetal cells for clinical responsiveness. This understanding provides exciting opportunities to utilize oncofetal niche characteristics as biomarkers of immunotherapy response in HCC and might also have validity for predicting responses to immunotherapy in other cancers. In this review, we explore the immunosuppressive mechanisms and interactions of oncofetal cells in the TME of HCC and their potential implications for immunotherapy response.

Plasmodium falciparum infection and disease in infancy associated with increased risk of malaria and anaemia in childhood.

BACKGROUND: Infants under 6 months of age are often excluded from malaria surveillance and observational studies. The impact of malaria during early infancy on health later in childhood remains unknown. METHODS: Infants from two birth cohorts in Malawi were monitored at quarterly intervals and whenever they were ill from birth through 24 months for Plasmodium falciparum infections and clinical malaria. Poisson regression and linear mixed effects models measured the effect of exposure to malaria in infancy on subsequent malaria incidence, weight-for-age z-scores (WAZ), and haemoglobin concentrations after 6 months. RESULTS: Infants with at least one P. falciparum infection during their first 6 months had increased incidence ratio (IRR) of P. falciparum infection (IRR = 1.27, 95% CI, 1.06-1.52) and clinical malaria (IRR = 2.37, 95% CI, 2.02-2.80) compared to infants without infection. Infants with clinical malaria had increased risk of P. falciparum infection incidence between 6 and 24 months (IRR = 1.64, 95% CI, 1.38-1.94) and clinical malaria (IRR = 1.85, 95% CI, 1.48-2.32). Exposure to malaria was associated with lower WAZ over time (p = 0.02) and lower haemoglobin levels than unexposed infants at every time interval (p = 0.02). CONCLUSIONS: Infants experiencing malaria infection or clinical malaria are at increased risk of subsequent infection and disease, have poorer growth, and lower haemoglobin concentrations.

Na2ZrFe(PO4)3─A Rhombohedral NASICON-Structured Material: Synthesis, Structure and Na-Intercalation Behavior.

A NASICON-structured earth-abundant mixed transition metal (TM) containing Na-TM-phosphate, viz., Na2ZrFe(PO4)3, has been prepared via a sol-gel route using a low-cost Fe3+-based precursor. The as-prepared material crystallizes in the desired rhombohedral NASICON structure (space group: R3̅c) at room temperature. Synchrotron X-ray diffraction (XRD), transmission electron microscopy, X-ray absorption spectroscopy, etc., have been performed to determine the crystal structure, associated details, composition, and electronic structures. In light of the structural features, as one of the possible functionalities of Na2FeZr(PO4)3, Na-intercalation/deintercalation has been examined, which indicates the occurrence of reversible electrochemical Na-insertion/extraction via Fe2+/Fe3+ redox at an average potential of ∼2.5 V. The electrochemical data and direct evidences from operando synchrotron XRD indicate that the rhombohedral structure is preserved during Na-insertion/extraction, albeit within a certain range of Na-content (i.e., ∼2-3 p.f.u.), beyond which rhombohedral → monoclinic transformation takes place. Within this range, Na-insertion/extraction takes place via solid-solution pathway, resulting in outstanding cyclic stability, higher Na-diffusivity, and good rate-capability. To the best of the authors' knowledge, this represents the first in-depth structural, compositional, and electrochemical studies with Na2ZrFe(PO4)3, along with the interplay between those, which provide insights into the design of similar low-cost materials for various applications, including sustainable electrochemical energy storage systems.

SpDamID: Marking DNA Bound by Protein Complexes Identifies Notch-Dimer Responsive Enhancers.

We developed Split DamID (SpDamID), a protein complementation version of DamID, to mark genomic DNA bound in vivo by interacting or juxtapositioned transcription factors. Inactive halves of DAM (DNA adenine methyltransferase) were fused to protein pairs to be queried. Either direct interaction between proteins or proximity enabled DAM reconstitution and methylation of adenine in GATC. Inducible SpDamID was used to analyze Notch-mediated transcriptional activation. We demonstrate that Notch complexes label RBP sites broadly across the genome and show that a subset of these complexes that recruit MAML and p300 undergo changes in chromatin accessibility in response to Notch signaling. SpDamID differentiates between monomeric and dimeric binding, thereby allowing for identification of half-site motifs used by Notch dimers. Motif enrichment of Notch enhancers coupled with SpDamID reveals co-targeting of regulatory sequences by Notch and Runx1. SpDamID represents a sensitive and powerful tool that enables dynamic analysis of combinatorial protein-DNA transactions at a genome-wide level.

Validation study of new clinical scoring - "Apollo Clinical Scoring system" for bladder pain syndrome/interstitial cystitis and comparison of outcome with standard "O'Leary-Sant score".

AIM: Validation of the recently published newer clinical scoring system for bladder pain syndrome/interstitial cystitis and comparison of the results with the pre-existing standard O'Leary-Sant score. INTRODUCTION: The symptoms are our primary guide to disease severity analysis, treatment, and response monitoring. The combined ICSI/ICPI (O'Leary-Sant Interstitial Cystitis Symptom and Problem Index) consist of a four-item symptom and problem index focusing on urgency, frequency, nocturia, and pain. A new scale, assigning more weight to pain and nocturia and adding the domains of sexual dysfunction and psychological impact, has been published by one of the authors (El Khoudary et al. J Women's Health 2002. 18:1361-1368; 7). MATERIAL AND METHODS: This is a prospective study conducted to validate a newer clinical scoring system, namedht e 'Apollo Clinical Scoring' (ACS) system for patients with bladder pain syndrome/ interstitial cystitis (BPS/IC), and to compare its outcome with the simultaneously applied standard O'Leary-Sant (OLS) score. Thirty-five patients of BPS/IC diagnosed using the ESSIC definition were enrolled in the study and followed for 6 months. Intraclass correlation coefficient (ICC) for test-retest reliability, and Cronbach's α for measure of internal consistency, were applied to both scoring systems. RESULTS: Intraclass correlation coefficient for ACS was 0.715 and for OLS was 0.689. Cronbach's α for ACS was 0.736 and for OLS was 0.698. CONCLUSION: The present study suggests that the recently devised Apollo Clinical Scoring (ACS) system for patients of BPS/IC is internally consistent and a reliable scoring system. When compared with OLS in parallel setting, the newer ACS appeared to be marginally better.

Chronic Inflammation's Transformation to Cancer: A Nanotherapeutic Paradigm.

The body's normal immune response against any invading pathogen that causes infection in the body results in inflammation. The sudden transformation in inflammation leads to the rise of inflammatory diseases such as chronic inflammatory bowel disease, autoimmune disorders, and colorectal cancer (different types of cancer develop at the site of chronic infection and inflammation). Inflammation results in two ways: short-term inflammation i.e., non-specific, involves the action of various immune cells; the other results in long-term reactions lasting for months or years. It is specific and causes angiogenesis, fibrosis, tissue destruction, and cancer progression at the site of inflammation. Cancer progression relies on the interaction between the host microenvironment and tumor cells along with the inflammatory responses, fibroblast, and vascular cells. The two pathways that have been identified connecting inflammation and cancer are the extrinsic and intrinsic pathways. Both have their own specific role in linking inflammation to cancer, involving various transcription factors such as Nuclear factor kappa B, Activator of transcription, Single transducer, and Hypoxia-inducible factor, which in turn regulates the inflammatory responses via Soluble mediators cytokines (such as Interleukin-6, Hematopoietin-1/Erythropoietin, and tumor necrosis factor), chemokines (such as Cyclooxygenase-2, C-X-C Motif chemokines ligand-8, and IL-8), inflammatory cells, cellular components (such as suppressor cells derived from myeloid, tumor-associated macrophage, and acidophils), and promotes tumorigenesis. The treatment of these chronic inflammatory diseases is challenging and needs early detection and diagnosis. Nanotechnology is a booming field nowadays for its rapid action and easy penetration inside the infected destined cells. Nanoparticles are widely classified into different categories based on their different factors and properties such as size, shape, cytotoxicity, and others. Nanoparticles emerged as excellent with highly progressive medical inventions to cure diseases such as cancer, inflammatory diseases, and others. Nanoparticles have shown higher binding capacity with the biomolecules in inflammation reduction and lowers the oxidative stress inside tissue/cells. In this review, we have overall discussed inflammatory pathways that link inflammation to cancer, major inflammatory diseases, and the potent action of nanoparticles in chronic inflammation-related diseases.

Delayed Compression Paralysis Following an Iliopsoas Hematoma 30 Days After Saw-Scaled Viper (Echis carinatus sochureki) Envenoming: A Case Report.

Snakebite envenoming is a neglected tropical disease disproportionately affecting the rural and marginalized population in low-middle-income countries. The saw-scaled viper (Echis carinatus) is a clinically important snake that causes serious morbidity and mortality in the Indian subcontinent. Even though it is within the so-called big-four snakes against which polyvalent antivenom is available throughout India, reports of antivenom ineffectiveness are emerging in saw-scaled viper envenoming, especially around Jodhpur, Rajasthan, India. This case report highlights a patient with saw-scaled viper envenoming with an ineffective antivenom response complicated by acute kidney injury as well as local and systemic bleeding complications, which subsequently resulted in a pelvic hematoma that compressed the lumbosacral nerves, causing lower-limb weakness and sensory deficits. He was successfully managed with hematoma aspiration and supportive care. This case brings into focus the challenges of managing saw-scaled viper envenoming in this region with antivenom ineffectiveness, resulting in delayed and significant coagulopathy and its complications leading to prolonged hospital stay and morbidity. Our report spotlights less emphasized aspects of long-term morbidity in snakebite survivors, such as loss of working days and productivity. We also highlight the need for an organized system of long-term follow-up of snakebite survivors to screen for possible complications and manage them early.

The Effect of Intermittent Preventive Treatment of Malaria During Pregnancy and Placental Malaria on Infant Risk of Malaria.

BACKGROUND: Intermittent preventive treatment of malaria during pregnancy (IPTp) with dihydroartemisinin-piperaquine (DP) provides greater protection from placental malaria than sulfadoxine-pyrimethamine (SP). Some studies suggest placental malaria alters risk of malaria infection in infants, but few have quantified the effect of IPTp on infant susceptibility to malaria. METHODS: Infants born to women enrolled in a randomized clinical trial comparing IPTp-SP and IPTp-DP in Malawi were followed from birth to 24 months to assess effect of IPTp and placental malaria on time to first malaria episode and Plasmodium falciparum incidence. RESULTS: In total, 192 infants born to mothers randomized to IPTp-SP and 195 randomized to IPTp-DP were enrolled. Infants in IPTp exposure groups did not differ significantly regarding incidence of clinical malaria (incidence rate ratio [IRR], 1.03; 95% confidence interval [CI], .58-1.86) or incidence of infection (IRR, 1.18; 95% CI, .92-1.55). Placental malaria exposure was not associated with incidence of clinical malaria (IRR, 1.03; 95% CI, .66-1.59) or infection (IRR, 1.15; 95% CI, .88-1.50). Infant sex, season of birth, and maternal gravidity did not confound results. CONCLUSIONS: We did not find evidence that IPTp regimen or placental malaria exposure influenced risk of malaria during infancy in this population. Clinical Trials Registration. NCT03009526.

Plasmodium falciparum in Aotus nancymaae: A New Model for Placental Malaria.

Plasmodium falciparum-infected erythrocytes that display the variant surface antigen VAR2CSA bind chondroitin sulfate A (CSA) to sequester in placental intervillous spaces, causing severe sequelae for mother and offspring. Here, we establish a placental malaria (PM) monkey model. Pregnant Aotus infected with CSA-binding P. falciparum CS2 parasites during the third trimester developed pronounced sequestration of late-stage parasites in placental intervillous spaces that express VAR2CSA and bind specifically to CSA. Similar to immune multigravid women, a monkey infected with P. falciparum CS2 parasites over successive pregnancies acquired antibodies against VAR2CSA, with potent functional activity that was boosted upon subsequent pregnancy infections. Aotus also developed functional antibodies after multiple acute PM episodes and subsequent VAR2CSA immunization. In summary, P. falciparum infections in pregnant Aotus monkeys recapitulate all the prominent features of human PM infection and immunity, and this model can be useful for basic mechanistic studies and preclinical studies to qualify candidate PM vaccines. Clinical Trials Registration: NCT02471378.

Author Reply: Comparison of Norepinephrine and Terlipressin vs Norepinephrine Alone for Management of Septic Shock: A Randomized Control Study.

How to cite this article: Sahoo P, Kothari N, Sharma A, Goyal S. Author Reply: Comparison of Norepinephrine and Terlipressin vs Norepinephrine Alone for Management of Septic Shock: A Randomized Control Study. Indian J Crit Care Med 2023;27(8):603-604.

Comparison of Diagnostic Accuracy of Presepsin and Procalcitonin for Sepsis in Critically Ill Patients: A Prospective Observational Study.

Objective: Early diagnosis of sepsis is crucial to institute appropriate therapy and then to avert a possible negative outcome. We planned this study to evaluate the diagnostic value of presepsin, its sensitivity and specificity for diagnosing sepsis in critically ill patients, and its ability to prognosticate the outcome of sepsis. Methods: In this prospective observational study, adult patients admitted to the intensive care unit (ICU) at our institute were screened, and those with features suggestive of sepsis were recruited into the study. Procalcitonin (PCT) and presepsin were assessed on the day of admission and day 7 of the ICU stay, apart from routine investigations. Patients were followed for outcome in terms of mortality till 28 days. Results: The study comprised 82 patients who satisfied the inclusion criteria. Presepsin sensitivity for sepsis diagnosis was determined to be 78%, while that of PCT was determined to be 69%. This gave a combined sensitivity of presepsin and PCT of 93% when used in parallel for the diagnosis of sepsis. Conclusion: A combination of PCT and presepsin provides higher sensitivity and can be used to screen for sepsis in the ICU. How to cite this article: Roy S, Kothari N, Sharma A, Goyal S, Sankanagoudar S, Bhatia PK, et al. Comparison of Diagnostic Accuracy of Presepsin and Procalcitonin for Sepsis in Critically Ill Patients: A Prospective Observational Study. Indian J Crit Care Med 2023;27(4):289-293.