Long-Lasting Insecticidal Net Coverage and Utilization in Burla Town of Sambalpur District: A Cross-Sectional Study.

Background Vector-borne diseases continue to significantly contribute to mortality and morbidity, especially in developing nations. Vector management is a key pillar in combating these diseases, and long-lasting insecticidal nets (LLINs) are cost-effective tools. The Government of India, under the National Vector Borne Disease Control Programme (NVBDCP), has distributed LLINs for free to increase coverage and utilization. This study aims to estimate the coverage and utilization of LLINs in Burla town. Method This cross-sectional study was conducted from October to December 2022 in Burla town of Sambalpur in Odisha, India. The estimated sample size was 510 households, assuming 50% coverage. Multi-stage cluster sampling was adopted to select the Anganwadi centers and households. A pretested questionnaire was utilized for data collection by trained personnel through Epicollect5 (Centre for Genomic Pathogen Surveillance, Oxford, UK). Logistic regression was used to identify predictors for LLIN usage. Results The survey covered 516 households with 2,541 individuals and 1,165 nets. Household-level coverage was 94.2%, and regular utilization was 45.74%. Skin reactions (35.7%) were the most common reason for non-usage, followed by low mosquito density (12%). Logistic regression showed that the number of rooms (adjusted odds ratio (AOR) = 0.663, p = 0.012), number of bed nets (AOR = 2.757, p < 0.001), knowledge of malaria (AOR = 2.92, p = 0.04), adopting other measures for mosquito control (AOR = 0.295, p < 0.001), and washing the net (AOR = 1.92, p = 0.028) significantly predicted sleeping under mosquito net. Conclusion Our study has depicted high coverage of LLINs in Burla town, but utilization needs further improvement. Counseling regarding proper use can decrease the skin reactions responsible for non-usage. Regular health education programs are required to emphasize the benefits of LLIN use, along with regular monitoring and supervision.

The Pattern of Health-Seeking Behavior among Juang Tribe- A Particularly Vulnerable Tribal Group of Odisha, India.

Introduction: Social and economic position, environment, access to healthcare, ethos, and worldview are all important determinants of people's health-seeking behavior. Tribal communities in India oscillate between their emic rationale for the cause and treatment of health concerns on the one hand and affordable modern methods on the other. The present article is based on a study conducted among the Junag tribe of Odisha to understand their acceptance and preference for traditional or modern healthcare systems and the reasons for these choices. Material and Methods: Purposive sampling, a pre-structured schedule, an observation approach, case studies, and interviews with community members have been used to gather the primary data used in the study. Result: The study identified a diverse pattern of health-seeking behavior. From the four villages, 70% of respondents combined into cluster-1 preferred the traditional healthcare system, mostly for geographical and cultural reasons, as opposed to 95% of respondents from the villages in cluster-2, who preferred modern healthcare services because they were more easily accessible and involved modern healthcare providers. Conclusion: In this research work, it has been found that the Juang tribe is in a transitional phase and uses a hybrid approach to health seeking. Moreover, it has also been discovered that important variables including cultural attitudes and the affordability of contemporary healthcare services have influenced people's decisions toward healthcare systems.

Pneumothorax in Acute Neurologically Ill COVID-19 Positive Patients: A Brief Report.

Background: Pneumothorax is reported as a complication of coronavirus disease-2019 (COVID-19). The present report describes the incidence, clinical characteristics, and outcomes of pneumothorax in acute neurologically ill COVID-19 positive patients admitted to the COVID-19 neuro-intensive care unit (CNICU). Methods: In this retrospective study, pneumothorax was identified by reviewing chest radiographs of acute neurologically ill patients with and without associated COVID-19 admitted to the CNICU and non-COVID-19 NICU, respectively, from July to November 2020. The clinico-epidemiological characteristics of acute neurologically ill COVID-19 positive patients with pneumothorax are described. Results: The incidence of pneumothorax was 17% (8/47) in acute neurologically ill COVID-19 positive patients in the CNICU and 14.6% (6/41) in patients who received mechanical ventilation (MV). In contrast, the incidence of pneumothorax in acute neurologically ill non-COVID-19 patients admitted to the NICU was 3.7% (7/188) and 0.69% (1/143) in patients receiving MV. Conclusion: In our study, the incidence of pneumothorax was higher in patients with concomitant neurological and COVID-19 diseases than in acute neurologically ill non-COVID-19 patients managed during the same period in the ICUs.

Case report: Blotchy skin in a puffy neonate: is there a new association?

Introduction: Purpura fulminans in the neonatal population is a rare but potentially life-threatening condition complicated by thrombosis, resultant vital organ necrosis, and gangrene of the extremities. Considering the rapid evolution of the pathogenetic mechanism, an index of suspicion, early identification, and prompt intervention are imperative for improved outcomes. The majority of purpura fulminans cases have an infectious etiology, but it is essential to consider other congenital and acquired causes. Case description: We present a clinical case of a female neonate to emphasize the correlation between purpura fulminans, congenital chylothorax, involvement of the PAK2 gene, and the occurrence of retinal detachment in both eyes. After draining the congenital chylothorax, the neonate developed purpura fulminans due to a loss of protein C, S, and antithrombin factors, previously not reported in the literature. The purpuric lesions resolved after the administration of fresh frozen plasma. Subsequently, no recurring purpura fulminans lesions were noted following the normalization of the antithrombotic factor levels in the serum. Subsequently, the child also developed retinal detachment in both eyes.

H-atom site exchange in an iridium trans-dihydrogen/hydride complex, trans-[Ir(H)(η2-H2)(iPr)4(POCOP)(DMAP)].

Treatment of trans-[Ir(H)(N)2(iPr)4(POCOP)(DMAP)][BAr4f] (2) with H2 (1 bar) under ambient conditions (298 K) results in the formation of a trans-[Ir(H)(η2-H2)(iPr)4(POCOP)(DMAP)][BAr4f] (3) complex. Complex 3 exhibits H-atom site exchange between the bound H2 and the hydride ligands which are mutually trans to one another. A plausible mechanism of this exchange involves metal-ligand cooperativity as studied by computations.

Comparison of Four Risk of Malignancy Indices for Preoperative Evaluation of Ovarian Masses: A Prospective Observational Study.

BACKGROUND: Ovarian cancer imposes a significant health burden worldwide. Although various tumor markers are available to diagnose ovarian cancer, low-resource countries like India require a humble marker or index. The Risk of Malignancy Index (RMI) has been found to be a simple yet promising tool that can be used for this purpose. In this study, we attempted to validate various RMIs with the help of menopausal status, ultrasonogram score, cancer antigen (CA) 125 value and compare all four RMIs, which would be useful to differentiate benign and malignant ovarian masses. This could be an essential tool, especially in low-resource settings. METHOD: This prospective study was conducted at Kalinga Institute of Medical Sciences in Odisha, India, from September 2020 to September 2022 involving 191 patients with ovarian mass with histopathology, which was deemed the "gold standard" diagnostic tool. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of RMI 1, 2, 3, and 4 were calculated and compared.  Results: Out of 191 patients, 32 (16%) had malignancy and 159 (83.2%) had benign pathology. It was apparent that RMI 4 was a better tool for the initial assessment of patients with ovarian masses with a sensitivity of 80.6%, specificity of 96.2%, PPV of 81%, NPV of 96% at a cutoff of 334, and an area under the curve value of 0.939. CONCLUSION: RMI 4 followed by RMI 3 were relatively better indices than RMI 1 and RMI 2 for identifying benign and malignant ovarian masses. RMI 4 was a valuable and applicable method in diagnosing pelvic masses with a high risk of malignancy.

Neurodevelopmental Outcomes of Preterm Infants Born <29 Weeks with Bronchopulmonary Dysplasia-Associated Pulmonary Hypertension: A Multicenter Study.

OBJECTIVE: This study aimed to determine neurodevelopmental outcomes of preterm infants born at <29 weeks' gestational age (GA) with bronchopulmonary dysplasia and pulmonary hypertension (BPD-PH) at 18 to 24 months' corrected age (CA). STUDY DESIGN: In this retrospective cohort study, preterm infants born at <29 weeks' GA between January 2016 and December 2019, admitted to level 3 neonatal intensive care units, who developed BPD and were evaluated at 18 to 24 months' CA in the neonatal follow-up clinics were included. We compared demographic characteristics and neurodevelopmental outcomes between the two groups: Group I: BPD with PH and Group II: BPD with no PH, using univariate and multivariate regression models. The primary outcome was a composite of death or neurodevelopmental impairment (NDI). NDI was defined as any Bayley-III score < 85 on one or more of the cognitive, motor, or language composite scores. RESULTS: Of 366 eligible infants, 116 (Group I [BPD-PH] =7, Group II [BPD with no PH] = 109) were lost to follow-up. Of the remaining 250 infants, 51 in Group I and 199 in Group II were followed at 18 to 24 months' CA. Group I and Group II had median (interquartile range [IQR]) birthweights of 705 (325) and 815 g (317; p = 0.003) and median GAs (IQR) were 25 (2) and 26 weeks (2; p = 0.015) respectively. Infants in the BPD-PH group (Group I) were more likely to have mortality or NDI (adjusted odds ratio: 3.82; bootstrap 95% confidence interval; 1.44-40.87). CONCLUSION: BPD-PH in infants born at <29 weeks' GA is associated with increased odds of the composite outcome of death or NDI at 18 to 24 months' CA. KEY POINTS: · Long-term neurodevelopmental follow-up of preterm infants born <29 weeks' GA.. · Association of neurodevelopmental outcomes with BPD-associated PH.. · Need for longitudinal follow-up of children with BPD-associated PH..

CLU (clusterin) promotes mitophagic degradation of MSX2 through an AKT-DNM1L/Drp1 axis to maintain SOX2-mediated stemness in oral cancer stem cells.

Mitophagy regulates cancer stem cell (CSC) populations affecting tumorigenicity and malignancy in various cancer types. Here, we report that cisplatin treatment led to the activation of higher mitophagy through regulating CLU (clusterin) levels in oral CSCs. Moreover, both the gain-of-function and loss-of-function of CLU indicated its mitophagy-specific role in clearing damaged mitochondria. CLU also regulates mitochondrial fission by activating the Ser/Thr kinase AKT, which triggered phosphorylation of DNM1L/Drp1 at the serine 616 residue initiating mitochondrial fission. More importantly, we also demonstrated that CLU-mediated mitophagy positively regulates oral CSCs through mitophagic degradation of MSX2 (msh homeobox 2), preventing its nuclear translocation from suppressing SOX2 activity and subsequent inhibition of cancer stemness and self-renewal ability. However, CLU knockdown disturbed mitochondrial metabolism generating excessive mitochondrial superoxide, which improves the sensitivity to cisplatin in oral CSCs. Notably, our results showed that CLU-mediated cytoprotection relies on SOX2 expression. SOX2 inhibition through genetic (shSOX2) and pharmacological (KRX-0401) strategies reverses CLU-mediated cytoprotection, sensitizing oral CSCs toward cisplatin-mediated cell death.

Envelope Glycoprotein based multi-epitope vaccine against a co-infection of Human Herpesvirus 5 and Human Herpesvirus 6 using in silico strategies.

The Human Betaherpesviruses HHV-5 and HHV-6 are quite inimical in immunocompromised hosts individually. A co-infection of both has been surmised to be far more disastrous. This can be attributed to a synergetic effect of their combined pathologies. While there have been attempts to develop a vaccine against each virus, no efforts were made to contrive an effective prophylaxis for the highly detrimental co-infection. In this study, an ensemble of viral envelope glycoproteins from both the viruses was utilized to design a multi-epitope vaccine using immunoinformatics tools. A collection of bacterial protein toll-like receptor agonists (BPTAs) was screened to identify a highly immunogenic adjuvant for the vaccine construct. The constructed vaccine was analysed using an array of methodologies ranging from World population coverage analysis to Immune simulation, whose results indicate high vaccine efficacy and stability. Furthermore, codon optimization and in silico cloning analysis were performed to check for efficient expression in a bacterial system. Collectively, these findings demonstrate the potential of the constructed vaccine to elicit an immune response against HHV-5 and HHV-6, thus supporting the viability of in vitro and in vivo studies.

Fetomaternal Outcomes in Women Affected With Preterm Premature Rupture of Membranes: An Observational Study From a Tertiary Care Center in Eastern India.

INTRODUCTION: Preterm premature rupture of membranes (PPROM) is the spontaneous rupture of the fetal membranes before the completion of 37 weeks of pregnancy. PPROM occurs in 3% of pregnancies. METHODOLOGY: This prospective observational study was conducted between September 2019 and March 2021, involving 150 antenatal patients attending our outpatient department or labor room. All pregnant women with a singleton pregnancy between 28 and 37 weeks of gestational age with PPROM were included in our study. RESULTS: A total of 44% of women were admitted to the hospital within 6-11 hours of the onset of PPROM, while 34% of women were admitted within five hours and 15.33% were admitted within 12-23 hours of the onset of PPROM. The most common organisms isolated in high vaginal swabs were Enterococcus faecalis (18%), Escherichia coli (12%), Staphylococcus aureus (12.66%), Staphylococcus haemolyticus (6.66%), and Candida albicans (4.66%). Around 74.66% of women were delivered within 24 hours of the onset of PPROM, whereas only 2.6% of patients were delivered after 72 hours and the rest 34% were delivered between 25 and 72 hours. Of our study subjects, 10% were febrile, 4% were having urinary tract infections, 2.5% had postpartum hemorrhage, and 2% had chorioamnionitis. As far as neonatal morbidity and mortality are concerned, birth asphyxia and jaundice were seen in 12% of patients each, whereas septicemia was found in 4% of study subjects. CONCLUSION: Owing to the association of higher maternal and perinatal morbidity and mortality, cases, especially in the early PPROM group, should be strictly monitored for clinical and laboratory signs of chorioamnionitis while opting for conservative management.

Neonatal Joubert Syndrome With Renal Involvement and Respiratory Distress.

Joubert syndrome (JS) is a rare autosomal recessive neurodevelopmental disorder with characteristic clinical presentation of hyperpnea-apnea spells, hypotonia, dysmorphic facies, and nystagmus and imaging features of molar tooth sign and cerebellar vermian hypoplasia-dysplasia. Early diagnosis is needed for timely management and favorable outcome. We present a case of neonatal JS with renal involvement presenting with respiratory distress and highlight the characteristic clinical and imaging findings. On examination, the baby had low set ears, a large protruding tongue, hypertelorism, and a depressed nasal bridge. Ultrasonography (USG) abdomen showed echogenic kidneys with cortical and medullary cysts. Magnetic Resonance Imaging (MRI) brain showed classical molar tooth sign, vermian hypoplasia-dysplasia, and thinning of the corpus callosum.

Metabolomics of Multimorbidity: Could It Be the Quo Vadis?

Multimorbidity, the simultaneous presence of two or more chronic diseases, affects the health care to a great extent. Its association with health care cost, more disability, and poor quality of life makes it a major public health risk. The matter of worry is that management of a multimorbid condition is complicated by the fact that multiple types of treatment may be required to treat different diseases at a time, and the interaction between some of the therapies can be detrimental. Understanding the causal factors of simultaneously occurring disease conditions and investigating the connected pathways involved in the whole process may resolve the complication. When different disease conditions present in an individual share common responsible factors, treatment strategies targeting at those common causes will certainly reduce the chance of development of multimorbidity occurring because of those factors. Metabolomics that can dig out the underlying metabolites/molecules of a medical condition is believed to be an effective technique for identification of biomarkers and intervention of effective treatment strategies for multiple diseases. We hypothesize that understanding the metabolic profile may shed light on targeting the common culprit for different/similar chronic diseases ultimately making the treatment strategy more effective with a combinatorial effect.

Urinary MMP-7: A Predictive, Noninvasive Early Marker for Chronic Kidney Disease Development in Patients with Hypertension.

OBJECTIVE: Upregulation of matrix metalloproteinase-7 (MMP-7) is associated with hypertension and kidney fibrosis, which can progress to chronic kidney disease (CKD). Currently, kidney fibrosis is only detectable by an invasive procedure. Therefore, we set out to determine whether MMP-7 can act as a noninvasive biomarker in patients with hypertension to enable early detection of kidney fibrosis. MATERIALS AND METHODS: Diagnosed patients with hypertension and control patients were sampled. We diagnosed CKD using clinical and laboratory parameters. Serum urea, creatinine, urinary microalbumin, the albumin-to-creatinine ratio, and urinary MMP-7 were analyzed. RESULTS: The 195 patients with hypertension had significantly elevated MMP-7. Of these patients, 166 had MMP-7 >25.8 µg/L, whereas only 29 had MMP-7 <25.8 µg/L. Thirty-two patients with hypertension showed features of CKD, all of whom had urinary MMP-7 >25.8 µg/L. However, the urinary MMP-7 level did not differ with the severity of CKD or with the duration of hypertension. CONCLUSION: Elevated urinary MMP-7 can be a potential noninvasive, early indicator in patients with hypertension progressing to CKD, thus enabling early therapeutic intervention.

A robust dual interval type-2 fuzzy lead-lag based UPFC for stability enhancement using Harris Hawks Optimization.

A Harris Hawks Optimization (HHO)tuned dual interval type-2 fuzzy lead-lag (Dual-IT2FLL) based unified power flow controller (UPFC) is proposed to minimize oscillations in single and multimachine power systems. The proposed damping controller coordinates between the modulation index (MI) and phase angle of series and shunt converters of UPFC simultaneously and is designed using speed deviation, a remote input signal for stability improvement. The performance of the proposed controller is verified through nonlinear time and frequency domain simulations under different operating conditions. The graphical simulations and validations using OPAL-RT OP5600 are presented to access the stability performance. Comparison based on different performance indices (PIs), like mean, standard deviation, overshoots and settling time are also considered to prove the better performance of the proposed HHO tuned dual-IT2FLL based UPFC over others under different operating conditions.

Clinical biomarkers in soft tissue sarcoma A comprehensive review of current soft tissue sarcoma biomarkers.

Soft tissue sarcomas (STS) are a heterogeneous group of tumors that arise from mesenchymal tissue. Investigation at the molecular level has been challenging due to the rarity of STS and the number of histologic subtypes. However, recent research has provided new insight into potential genomic, proteomic, and immunological biomarkers of STS. The identification of biomarkers can improve diagnosis, prognosis, and prediction of recurrence and treatment response. This review provides an understanding of biomarkers, discussing the current status of biomarker research in STS.

Autophagy-modulating phytochemicals in cancer therapeutics: Current evidences and future perspectives.

Autophagy is an intracellular catabolic self-cannibalism that eliminates dysfunctional cytoplasmic cargos by the fusion of cargo-containing autophagosomes with lysosomes to maintain cyto-homeostasis. Autophagy sustains a dynamic interlink between cytoprotective and cytostatic function during malignant transformation in a context-dependent manner. The antioxidant and immunomodulatory phyto-products govern autophagy and autophagy-associated signaling pathways to combat cellular incompetence during malignant transformation. Moreover, in a close cellular signaling circuit, autophagy regulates aberrant epigenetic modulation and inflammation, which limits tumor metastasis. Thus, manipulating autophagy for induction of cell death and associated regulatory phenomena will embark on a new strategy for tumor suppression with wide therapeutic implications. Despite the prodigious availability of lead pharmacophores in nature, the central autophagy regulating entities, their explicit target, as well as pre-clinical and clinical assessment remains a major question to be answered. In addition to this, the stage-specific regulation of autophagy and mode of action with natural products in regulating the key autophagic molecules, control of tumor-specific pathways in relation to modulation of autophagic network specify therapeutic target in caner. Moreover, the molecular pathway specificity and enhanced efficacy of the pre-existing chemotherapeutic agents in co-treatment with these phytochemicals hold high prevalence for target specific cancer therapeutics. Hence, the multi-specific role of phytochemicals in a cellular and tumor context dependent manner raises immense curiosity for investigating of novel therapeutic avenues. In this perspective, this review discusses about diverse implicit mechanisms deployed by the bioactive compounds in diagnosis and therapeutics approach during cancer progression with special insight into autophagic regulation.

Clinical Characteristics and Outcomes of Critically Ill Neurological Patients with COVID-19 Infection in Neuro-intensive Care Unit: A Retrospective Study.

BACKGROUND: There are insufficient data about clinical outcomes in critically ill neurological patients with concomitant coronavirus disease (COVID-19). This study describes the clinical characteristics, predictors of mortality, and clinical outcomes in COVID-19-positive neurological patients managed in a dedicated COVID-19 neurointensive care unit (CNICU). METHODS: This single-center, retrospective cohort study was conducted in critically ill neurological and neurosurgical patients with concomitant COVID-19 infection admitted to the CNICU at the National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, from July to November 2020. Patients' demographic, clinical, laboratory, imaging, treatment, and outcome data were retrieved from the manual and electronic medical records. Predictors of mortality and neurological outcome were identified using logistic regression. RESULTS: During the study period, 50 COVID-19-positive neurological patients were admitted to the CNICU. Six patients were excluded from the analysis as they were managed in the CNICU for <24 hours. A poor outcome, defined as death or motor Glasgow Coma Scale <5 at hospital discharge, was observed in 34 of 44 patients (77.27%) with inhospital mortality in 26 of 44 patients (59%). Worst modified sequential organ failure assessment (MSOFA) score, lactate dehydrogenase maximum levels (LDHmax), and lymphocyte count were predictors of inhospital mortality with an odds ratio (OR) of 1.88, 1.01, and 0.87, respectively, whereas worst MSOFA and LDHmax levels were predictors for poor neurological outcome with OR of 1.99 and 1.01, respectively. CONCLUSIONS: Mortality is high in neurological patients with concomitant COVID-19 infection. Elevated inflammatory markers of COVID-19 suggest the role of systemic inflammation on clinical outcomes. Predictors of mortality and poor outcome were higher MSOFA score and elevated LDH levels. Additionally, lymphopenia was associated with mortality. HOW TO CITE THIS ARTICLE: Surve RM, Mishra RK, Malla SR, Kamath S, Chakrabarti DR, Kulanthaivelu K, et al. Clinical Characteristics and Outcomes of Critically Ill Neurological Patients with COVID-19 Infection in Neuro-intensive Care Unit: A Retrospective Study. Indian J Crit Care Med 2021;25(10):1126-1132.

IgG Immune Complexes Inhibit Naïve T Cell Proliferation and Suppress Effector Function in Cytotoxic T Cells.

Elevated levels of circulating immune complexes are associated with autoimmunity and with worse prognoses in cancer. Here, we examined the effects of well-defined, soluble immune complexes (ICs) on human peripheral T cells. We demonstrate that IgG-ICs inhibit the proliferation and differentiation of a subset of naïve T cells but stimulate the division of another naïve-like T cell subset. Phenotypic analysis by multi-parameter flow cytometry and RNA-Seq were used to characterize the inhibited and stimulated T cells revealing that the inhibited subset presented immature features resembling those of recent thymic emigrants and non-activated naïve T cells, whereas the stimulated subset exhibited transcriptional features indicative of a more differentiated, early memory progenitor with a naïve-like phenotype. Furthermore, we show that while IgG1-ICs do not profoundly inhibit the proliferation of memory T cells, IgG1-ICs suppress the production of granzyme-ß and perforin in cytotoxic memory T cells. Our findings reveal how ICs can link humoral immunity and T cell function.

Passiflora edulis (var. Flavicarpa) Juice Supplementation Mitigates Isoproterenol-induced Myocardial Infarction in Rats.

The common reason for mortality globally is myocardial infarction. The study aimed to evaluate Passiflora edulis (PE) fruit juice potential in the experimental isoproterenol (ISO) treated rat model to manage myocardial injury. ISO (20 mg/100 g body weight) treated rats showed a significant increment in serum marker enzymes lactate dehydrogenase (LDH) and creatinine kinase (CK), serum glutamate pyruvate transaminase (SGPT), serum glutamate oxaloacetate transaminase (SGOT), serum alkaline phosphatase (ALP) and serum acid phosphatase (ACP) activity. Besides, phosphorus and calcium, serum cholesterol, and triglyceride levels (TG) were high in ISO groups. A significant decline in antioxidant activity and histopathological alteration was observed in ISO treated groups. PE juice pre-treatment (2 ml/kg) for 28 days and ISO treatment on the 29th and 30th days showed a protective effect on distorted biochemical and histopathologic parameters compared with reference drug metoprolol. These findings indicate the cardioprotective effect of PE juice on ISO-induced myocardial infracted rats.

Ethnic Differences in the Smoking-related Risk of Inflammatory Bowel Disease: A Systematic Review and Meta-analysis.

BACKGROUND AND AIMS: The association between smoking and inflammatory bowel disease [IBD] relies on old meta-analyses including exclusively non-Jewish White populations. Uncertainty persists regarding the role of smoking in other ethnicities. METHODS: We systematically searched Medline/PubMed, Embase, and Scopus for studies examining tobacco smoking and the risk of developing IBD, ie, Crohn's disease [CD] or ulcerative colitis [UC]. Two authors independently extracted study data and assessed each study's risk of bias. We examined heterogeneity and small-study effect, and calculated summary estimates using random-effects models. Stratified analyses and meta-regression were employed to study the association between study-level characteristics and effect estimates. The strength of epidemiological evidence was assessed through prespecified criteria. RESULTS: We synthesised 57 studies examining the smoking-related risk of developing CD and UC. Non-Jewish White smokers were at increased risk of CD (29 studies; relative risk [RR]: 1.95, 95% confidence interval [CI]: 1.69‒2.24; moderate evidence). No association was observed in Asian, Jewish. and Latin-American populations [11 studies; RR: 0.97; 95% CI: 0.83-1.13], with no evidence of heterogeneity across these ethnicities. Smokers were at reduced risk of UC [51 studies; RR: 0.55, 95% CI: 0.48-0.64; weak evidence] irrespectively of ethnicity; however, cohort studies, large studies, and those recently published showed attenuated associations. CONCLUSIONS: This meta-analysis did not identify any increased risk of CD in smokers in ethnicities other than non-Jewish Whites, and confirmed the protective effect of smoking on UC occurrence. Future research should characterise the genetic background of CD patients across different ethnicities to improve our understanding of the role of smoking in CD pathogenesis.