Retrospective review of growth in pediatric intestinal failure after weaning from parenteral nutrition.

BACKGROUND: Growth outcomes in children with intestinal failure (IF) after weaning from parenteral nutrition (PN) may be modified by primary diagnosis and interventions aimed at achieving enteral tolerance. We evaluated growth after weaning by diagnosis and intestinal transplant status and during treatment with the glucagon-like peptide-2 analog teduglutide. METHODS: A two-center retrospective review was conducted on children diagnosed with IF at age <12 months. The z scores for weight and length/height were examined up to 5 years after PN weaning and in children who received teduglutide for >6 months. Data were reported as median and interquartile range (IQR). RESULTS: A total of 362 children (58% male and 72% White) were reviewed; 41% (n = 150) weaned from PN at age 1.5 years (IQR = 0.96-3). Weight and length/height data were available for 144 children; 46 received an intestinal transplant. Median weight and length/height z scores at weaning were -1.15 (IQR = -2.09 to -0.39) and -1.89 (IQR = -2.9 to -1.02), respectively. In those not transplanted, z scores remained stable (± 0.5 change). Children with small bowel atresia experienced accelerated linear growth (> +0.5 change) beginning in year 3. Most children transplanted experienced growth acceleration beginning in year 2. Fourteen children received teduglutide (median = 840 [IQR = 425-1530] days), and growth remained stable throughout treatment. Five were weaned from PN within 1 year. CONCLUSION: We observed stable growth with limited catch-up after PN weaning, with minimal variation by diagnosis, and during teduglutide therapy. Children who received an intestinal transplant experienced acceleration in weight and linear growth after weaning.

Redescription of Dracovermis occidentalis (Digenea: Liolopidae) infecting American alligator, Alligator mississippiensis from the Bon-Secour River (Mobile-Tensaw River Delta, Alabama, USA) and a revised phylogeny for Liolopidae.

We examined several American alligators, Alligator mississippiensis (Daudin, 1802) (Crocodilia: Alligatoridae) from Louisiana, Alabama, and South Carolina in August 2022. The intestine of one alligator from Alabama was infected by Dracovermis occidentalis Brooks and Overstreet, 1978 (Platyhelminthes: Digenea: Liolopidae Odhner, 1912), a seldom collected and incompletely described trematode that lacks a representative nucleotide sequence. Liolopidae comprises 5 genera and 15 species: Liolope spp. infect giant salamanders; Helicotrema spp. infect turtles and lizards; Harmotrema spp. infect snakes; Paraharmotrema spp. infect turtles; and Dracovermis spp. infect crocodilians. Based on our study of the newly collected specimens and the holotype of D. occidentalis, we redescribe D. occidentalis, correct errors in its original description, and provide an updated phylogeny for Liolopidae that, for the first time, includes Dracovermis Brooks and Overstreet, 1978. Our specimens were identified as D. occidentalis by having testes in the posterior 1/3 of the body, a pretesticular cirrus sac, a spined and eversible cirrus, a bipartite seminal vesicle, and a post-acetabular vitellarium. A phylogenetic analysis of the D1-D3 domains of the nuclear large subunit ribosomal DNA (28S) recovered Liolopidae as monophyletic; however, low taxon sampling in the group precludes hypothesis-testing about liolopid-vertebrate cophyly. This is the first collection for morphological study of the type species for Dracovermis since the genus was proposed 46 years ago, the first record of a liolopid from Alabama, and the first phylogenetic analysis that includes Dracovermis.

Effects of Therapeutically Approved Individual Bile Acids on The Development of Metabolic Dysfunction-Associated Steatohepatitis a Low Bile Acid Mouse Model.

Bile acid (BA) signaling dysregulation is an important etiology for the development of Metabolic Dysfunction-associated Steatotic Liver Disease (MASLD). As diverse signaling molecules synthesized in the liver by pathways initiated with CYP7A1 and CYP27A1, BAs are endogenous modulators of farnesoid x receptor (FXR). FXR activation is crucial in maintaining BA homeostasis, regulating lipid metabolism, and suppressing inflammation. Additionally, BAs interact with membrane receptors and gut microbiota to regulate energy expenditure and intestinal health. Complex modulation of BAs in vivo and the lack of suitable animal models impede our understanding of the functions of individual BAs, especially during MASLD development. Previously, we determined that acute feeding of individual BAs differentially affects lipid, inflammation, and oxidative stress pathways in a low-BA mouse model, Cyp7a1/Cyp27a1 double knockout (DKO) mice. Currently, we investigated to what degree that cholic acid (CA), deoxycholic acid (DCA) or ursodeoxycholic acid (UDCA) at physiological concentrations impact MASLD development in DKO mice. The results showed that these three BAs varied in ability to activate hepatic and intestinal FXR, disrupt lipid homeostasis, and modulate inflammation and fibrosis. Additionally, UDCA activated intestinal FXR in these low-BA mice. Significant alterations in lipid uptake and metabolism in DKO mice following CA and DCA feeding indicate differences in cholesterol and lipid handling across genotypes. Overall, the DKO were less susceptible to weight gain, but more susceptible to MASH diet induced inflammation and fibrosis on CA and DCA supplement, while WT mice were more vulnerable to CA-induced fibrosis on control diet.

Lactated Ringers, albumin and mannitol as priming during cardiopulmonary bypass reduces pulmonary edema in rats compared with hydroxyethyl starch.

BACKGROUND: Endothelial disorders with edema formation and microcirculatory perfusion disturbances are common in cardiac surgery with cardiopulmonary bypass (CPB) and contribute to disturbed tissue oxygenation resulting in organ dysfunction. Albumin is protective for the endothelium and could be a useful additive to CPB circuit priming. Therefore, this study aimed to compare organ edema and microcirculatory perfusion in rats on CPB primed with lactated Ringers, albumin and mannitol (LR/albumin/mannitol) compared to 6% hydroxyethyl starch (HES). RESULTS: Male rats were subjected to 75 min of CPB primed with either LR/albumin/mannitol or with 6% HES. Renal and lung edema were determined by wet/dry weight ratio. Pulmonary wet/dry weight ratio was lower in rats on CPB primed with LR/albumin/mannitol compared to HES (4.77 [4.44-5.25] vs. 5.33 [5.06-6.33], p = 0.032), whereas renal wet/dry weight ratio did not differ between groups (4.57 [4.41-4.75] vs. 4.51 [4.47-4.73], p = 0.813). Cremaster microcirculatory perfusion was assessed before, during and after CPB with intravital microscopy. CPB immediately impaired microcirculatory perfusion compared to baseline (LR/albumin/mannitol: 2 [1-7] vs. 14 [12-16] vessels per recording, p = 0.008; HES: 4 [2-6] vs. 12 [10-13] vessels per recording, p = 0.037), which persisted after weaning from CPB without differences between groups (LR/albumin/mannitol: 5 [1-9] vs. HES: 1 [0-4], p = 0.926). In addition, rats on CPB primed with LR/albumin/mannitol required less fluids to reach sufficient flow rates (0.5 [0.0-5.0] mL vs. 9 [4.5-10.0], p < 0.001) and phenylephrine (20 [0-40] µg vs. 90 [40-200], p = 0.004). Circulating markers for inflammation (interleukin 6 and 10), adhesion (ICAM-1), glycocalyx shedding (syndecan-1) and renal injury (NGAL) were determined by ELISA or Luminex. Circulating interleukin-6 (16 [13-25] vs. 33 [24-51] ng/mL, p = 0.006), interleukin-10 (434 [295-782] vs. 2120 [1309-3408] pg/ml, p < 0.0001), syndecan-1 (5 [3-7] vs. 15 [11-16] ng/mL, p < 0.001) and NGAL (555 [375-1078] vs. 2200 [835-3671] ng/mL, p = 0.008) were lower in rats on CPB primed with LR/albumin/mannitol compared to HES. CONCLUSION: CPB priming with LR, albumin and mannitol resulted in less pulmonary edema, renal injury, inflammation and glycocalyx degradation compared to 6% HES. Furthermore, it enhanced hemodynamic stability compared with HES. Further research is needed to explore the specific role of albumin as a beneficial additive in CPB priming.

Resolved ALMA observations of water in the inner astronomical units of the HL Tau disk.

The water molecule is a key ingredient in the formation of planetary systems, with the water snowline being a favourable location for the growth of massive planetary cores. Here we present Atacama Large Millimeter/submillimeter Array data of the ringed protoplanetary disk orbiting the young star HL Tauri that show centrally peaked, bright emission arising from three distinct transitions of the main water isotopologue ( H 2 16 O ). The spatially and spectrally resolved water content probes gas in a thermal range down to the water sublimation temperature. Our analysis implies a stringent lower limit of 3.7 Earth oceans of water vapour available within the inner 17 astronomical units of the system. We show that our observations are limited to probing the water content in the atmosphere of the disk, due to the high dust column density and absorption, and indicate that the main water isotopologue is the best tracer to spatially resolve water vapour in protoplanetary disks.

Comparative immune profiling in survivors of the 2023 Nipah outbreak in Kerala state, India.

Immune profiling of Nipah virus (NiV) infection survivors is essential for advancing our understanding of NiV pathogenesis, improving diagnostic and therapeutic strategies, and guiding public health efforts to prevent future outbreaks. There is currently limited data available on the immune response to NiV infection. We aimed to elucidate the specific immune mechanisms involved in protection against NiV infection by analyzing the immune profiles of survivors of the Nipah outbreak in Kerala, India 2023. Immune cell populations were quantified and compared between survivors (up to 4 months post onset day of illness) and healthy controls. Statistical analysis was performed to explore associations between immune profiles and clinical outcomes. Immune signatures common to all three cases were: a heretofore undescribed persistent lymphopenia including the CD4+ Treg compartment with the relative expansion of memory Tregs; trends indicative of global leukopenic modulation were observed in monocytes and granulocytes including an expansion of putatively immunosuppressive low-density granulocytes described recently in the context of severe COVID-19; altered mucosal homing with respect to integrin beta-7 (ITGB7) expressing subsets; increased mobilization of activated T-cells (CD4+ and CD8+) and plasmablasts in the early phase of infection. Comparative analysis based on clinical presentation and outcome yielded lower initial viremia, increased activated T-cell responses, expanded plasmablasts, and restoration of ITGB7 expressing CD8+ T-cells as possible protective signatures. This longitudinal study delineates putative protective signatures associated with milder NiV disease. It emphasizes the need for the development of immunotherapeutic interventions such as monoclonal antibodies to blunt early viremia and ameliorate pathogenesis.

Promoting Independence Through Quality Dementia Care at Home (PITCH): An Australian Stepped-Wedge Cluster Randomised Controlled Trial Evaluating a Dementia Training Program for Home Care Workers.

OBJECTIVES: The primary aim of this pragmatic stepped-wedge cluster RCT was to determine the efficacy of a co-designed dementia specialist training program (the PITCH program) for home care workers (HCWs) to improve their confidence and knowledge when providing care for clients living with dementia. METHODS: HCWs who provided care to clients with dementia were recruited from seven home care service provider organisations in Australia between July 2019 and May 2022, and randomised into one of 18 clusters. The primary outcome was HCW's sense of self-competence in providing care services to people living with dementia at 6 months post PITCH training measured by the Sense of Competence in Dementia Care Staff (SCIDS) Scale. RESULTS: Two hundred and thirteen HCWS completed baseline assessment and almost half (48.4%) completed all three study assessments. HCWs in clusters that received PITCH training had significantly higher sense of competence (measured by SCIDS) than those who had not received PITCH training. Post hoc analysis revealed that face-to-face PITCH training consistently resulted in improvements in the HCWs sense of competence, dementia attitudes and knowledge when compared to online training and when compared to no training. PITCH training had no effect on the sense of strain HCWs felt in delivering dementia care. CONCLUSIONS: Given the majority of care for people living with dementia is provided at home by family carers supported by HCWs, it is essential that HCWs receive training that improves their skills in dementia care. This study is an important step towards better care at home for people living with dementia.

Does attachment anxiety mediate the persistence of anxiety and depressive symptoms from adolescence to early adulthood?

OBJECTIVES: Depression and anxiety often emerge in adolescence and persist into early adulthood. Developing a greater understanding of the factors that influence their persistence may inform psychological interventions. Their association with an insecure attachment style is well established although the mediating role of attachment anxiety in the persistence of depression and anxiety over time has not been examined. This study aimed to examine if anxious attachment mediated depression and anxiety from adolescence to early adulthood. METHODS: Data from 3,436 participants in a longitudinal birth cohort study were examined. At 14-years and 21-years, participants completed the Achenbach Youth Self Report (YSR) and the Achenbach Young Adult Self-Report (YASR) respectively. At 21-years, participants completed the Attachment Style Questionnaire (ASQ). Attachment anxiety as a mediator for the persistence of anxiety/depressive symptoms from 14- to 21-years was examined. RESULTS: Attachment anxiety accounted for approximately 60% of the persistence of anxiety and depressive symptoms at 14- and 21- years after adjusting for covariates. Results were similar when stratifying by males and females. CONCLUSIONS: Attachment anxiety significantly contributes to the persistence of anxiety and depressive symptoms from adolescence into early adulthood for both males and females. Incorporating interventions that address attachment anxiety in adolescents may improve the response to therapy for anxiety and depression.

Development of a New Tool to Combine the Promotion of Patient Mobility With Safe Patient Handling Equipment: The Johns Hopkins Safe Patient Handling Mobility (JH-SPHM) Guide.

BACKGROUND: Promoting safe patient mobility for providers and patients is a safety priority in the hospital setting. Safe patient handling equipment aids safe mobility but can also deter active movement by the patient if used inappropriately. Nurses need guidance to choose equipment that ensures their safety and that of the patients while promoting active mobility and preventing workplace-related injury. METHODS: Using a modified Delphi approach with a diverse group of experts, we created the Johns Hopkins Safe Patient Handling Mobility (JH-SPHM) Guide. This diverse group of 10 experts consisted of nurses, nurse leaders, physical and occupational therapists, safe patient handling committee representatives, and a fall prevention committee leader. The application of the tool was then tested in the hospital environment by two physical therapists. FINDINGS: Consensus was reached for safe patient handling (SPH) equipment recommendations at each level of the Johns Hopkins Mobility Goal Calculator (JH-Mobility Goal Calculator). Expert SPH equipment recommendations were then added to JH-Mobility Goal Calculator levels to create the JH-Safe Patient Handling Mobility Guide. JH-Safe Patient Handling Mobility Guide equipment suggestions were compared with equipment recommendations from physical therapists revealing strong agreement (n = 125, 88%). CONCLUSION: The newly created JH-Safe Patient Handling Mobility Guide provides appropriate safe patient-handling equipment recommendations to help accomplish patients' daily mobility goals. APPLICATIONS TO PRACTICE: The Johns Hopkins Safe Patient Handling Mobility Guide simultaneously facilitates patient mobility and optimizes safety for nursing staff through recommendations for safe patient-handling equipment for use with hospitalized patients.

Racial and Ethnic Differences in Emotional Reactions to the Flint Water Crisis among Michigan Women in Communities Outside of Flint.

Objective: To determine whether Black women in Michigan communities outside of Flint were more likely than women in other racial and ethnic groups to report negative emotional reactions to the Flint Water Crisis, an ongoing public health disaster that has been widely attributed to anti-Black structural racism. Methods: Data were from a 2020 survey of Michigan women aged 18-45 in communities outside of Flint (N=888). We used logistic regression models to examine racial and ethnic differences in the odds of negative emotional reactions to the Flint Water Crisis. Results: Compared with Black women, White women had lower odds of feeling scared (odds ratio [OR]=0.58; 95% CI, 0.40-0.84), hopeless (OR=0.53; 95% CI, 0.38-0.74), tired (OR=0.45; 95% CI, 0.32-0.64), and numb (OR=0.52; 95% CI, 0.35-0.75) when thinking about the water crisis. There were no differences between Black and Hispanic women, whereas women of other races or ethnicities had lower odds than Black women of feeling numb (OR=0.32; 95% CI, 0.14-0.72). Conclusions: The Flint Water Crisis was a racialized stressor, with potential implications for mental health inequities among Michigan women who were not directly affected by the crisis.

MICOS Complex Loss Governs Age-Associated Murine Mitochondrial Architecture and Metabolism in the Liver, While Sam50 Dictates Diet Changes.

The liver, the largest internal organ and a metabolic hub, undergoes significant declines due to aging, affecting mitochondrial function and increasing the risk of systemic liver diseases. How the mitochondrial three-dimensional (3D) structure changes in the liver across aging, and the biological mechanisms regulating such changes confers remain unclear. In this study, we employed Serial Block Face-Scanning Electron Microscopy (SBF-SEM) to achieve high-resolution 3D reconstructions of murine liver mitochondria to observe diverse phenotypes and structural alterations that occur with age, marked by a reduction in size and complexity. We also show concomitant metabolomic and lipidomic changes in aged samples. Aged human samples reflected altered disease risk. To find potential regulators of this change, we examined the Mitochondrial Contact Site and Cristae Organizing System (MICOS) complex, which plays a crucial role in maintaining mitochondrial architecture. We observe that the MICOS complex is lost during aging, but not Sam50. Sam50 is a component of the sorting and assembly machinery (SAM) complex that acts in tandem with the MICOS complex to modulate cristae morphology. In murine models subjected to a high-fat diet, there is a marked depletion of the mitochondrial protein SAM50. This reduction in Sam50 expression may heighten the susceptibility to liver disease, as our human biobank studies corroborate that Sam50 plays a genetically regulated role in the predisposition to multiple liver diseases. We further show that changes in mitochondrial calcium dysregulation and oxidative stress accompany the disruption of the MICOS complex. Together, we establish that a decrease in mitochondrial complexity and dysregulated metabolism occur with murine liver aging. While these changes are partially be regulated by age-related loss of the MICOS complex, the confluence of a murine high-fat diet can also cause loss of Sam50, which contributes to liver diseases. In summary, our study reveals potential regulators that affect age-related changes in mitochondrial structure and metabolism, which can be targeted in future therapeutic techniques.

Hotspot Exon 15 Mutations in BRAF Are Uncommon in Feline Tumours.

BRAF is one of multiple RAF proteins responsible for the activation of the MAPK cell signalling cascade involved in cell growth, differentiation, and survival. A hotspot BRAFV600E mutation, in exon 15, was determined to be a driver in 100% hairy cell leukaemias, 50%-60% of human melanomas, 30%-50% of human thyroid carcinomas and 10%-20% of human colorectal carcinomas. The orthologous BRAFV595E mutation was seen in 67% and 80% of canine bladder transitional cell carcinomas and prostatic adenocarcinomas, respectively. Since veterinary and human cancers exploit similar pathways and BRAF is highly conserved across species, BRAF can be expected to be a driver in a feline cancer. Primers were developed to amplify exon 15 of feline BRAF. One hundred ninety-six feline tumours were analysed. Sanger sequencing of the 211 bp PCR amplicon was done. A BRAF mutation was found in one tumour, a cutaneous melanoma. The mutation was a BRAFV597E mutation, orthologous to the canine and human hotspot mutations. A common synonymous variant, BRAFT586T, was seen in 23% (47/196) of tumours. This variant was suspected to be a single nucleotide polymorphism. BRAF was not frequently mutated in common feline tumours or in tumour types that frequently harbour BRAF mutations in human and canine cancers. As is seen in canine cancer genomics, the mutational profile in feline tumours may not parallel the histologic equivalent in human oncology.

Prescribing patterns and medications costs in patients on maintenance hemodialysis and peritoneal dialysis.

BACKGROUND AND HYPOTHESIS: Polypharmacy is a significant clinical issue for patients on dialysis but has been incompletely studied. We investigated the prevalence and costs of polypharmacy in a population-based cohort of participants treated with hemodialysis (HD) or peritoneal dialysis (PD). METHODS: We studied adults aged ≥ 20 years in Alberta, Canada receiving maintenance HD or PD as of March 31, 2019. We characterized participants as users of 0-29 drug categories of interest and those aged ≥ 65 as users/non-users of potentially inappropriate medications (PIM). We calculated the number of drug categories, daily pill burden, total annual cost, and annual cost per participant, and compared this to an age- and sex-matched cohort from the general Alberta population. RESULTS: Among 2 248 participants (mean age 63 years; 39% female) on HD (n = 1 781) or PD (n = 467), the median number of prescribed drug categories was 6 [interquartile range (IQR) 4, 8]; median daily pill burden was 8.0 (IQR 4.6, 12.6) pills/day, with 5% prescribed ≥ 21.7 pills/day, and 16.5% prescribed ≥ 15 pills/day. Twelve % were prescribed at least one drug that is contraindicated in kidney failure. The median annual per participant cost was ${\$}$3,831, totaling approximately ${\$}$11.6 million annually for all participants. When restricting to the 1 063 participants aged ≥ 65, the median number of PIM categories was 2 (IQR 1, 2), with a median PIM pill burden of 1.2 pills/day (IQR 0.5, 2.4). Compared to PD participants, HD participants had similar daily pill burden, higher use of PIM, and higher annual per participant cost. Pill burden and associated costs for participants on dialysis were more than 3-fold and 10-fold higher, respectively, compared to the matched participants from the general population. CONCLUSION: Participants on dialysis have markedly higher use of prescription medications and associated costs than the general population. Effective methods to de-prescribe in the dialysis population are needed.

Characterization of the zebrafish gabra1sa43718/sa43718 germline loss of function allele confirms a function for Gabra1 in motility and nervous system development.

Mutation of the GABRA1 gene is associated with neurodevelopmental defects and epilepsy. GABRA1 encodes for the α1 subunit of the γ-aminobutyric acid type A receptor (GABAAR), which regulates the fast inhibitory impulses of the nervous system. Multiple model systems have been developed to understand the function of GABRA1, but these models have produced complex and, at times, incongruent data. Thus, additional model systems are required to validate and substantiate previous results. We sought to provide initial phenotypic analysis of a novel germline mutant allele. Our analysis provides a solid foundation for the future use of this allele to characterize gabra1 functionally and pharmacologically using zebrafish. We investigated the behavioral swim patterns associated with a nonsense mutation of the zebrafish gabra1 (sa43718 allele) gene. The sa43718 allele causes a decrease in gabra1 mRNA expression, which is associated with light induced hypermotility, one phenotype previously associated with seizure like behavior in zebrafish. Mutation of gabra1 was accompanied by decreased mRNA expression of gabra2, gabra3, and gabra5, indicating a reduction in the expression of additional α sub-units of the GABAAR. Although multiple sub-units were decreased, larvae continued to respond to pentylenetetrazole (PTZ), indicating that a residual GABAAR exists in the sa43718 allele. Proteomics analysis demonstrated that mutation of gabra1 is associated with abnormal expression of proteins that regulate synaptic vesicle fusion, vesicle transport, synapse development, and mitochondrial protein complexes. These data support previous studies performed in a zebrafish nonsense allele created by CRISPR/Cas9 and validate that loss of function mutations in the gabra1 gene result in seizure-like phenotypes with abnormal development of the GABA synapse. Our results add to the existing body of knowledge as to the function of GABRA1 during development and validate that zebrafish can be used to provide complete functional characterization of the gene.

Ethylene Oxide in Southeastern Louisiana's Petrochemical Corridor: High Spatial Resolution Mobile Monitoring during HAP-MAP.

Ethylene oxide ("EtO") is an industrially made volatile organic compound and a known human carcinogen. There are few reliable reports of ambient EtO concentrations around production and end-use facilities, however, despite major exposure concerns. We present in situ, fast (1 Hz), sensitive EtO measurements made during February 2023 across the southeastern Louisiana industrial corridor. We aggregated mobile data at 500 m spatial resolution and reported average mixing ratios for 75 km of the corridor. Mean and median aggregated values were 31.4 and 23.3 ppt, respectively, and a majority (75%) of 500 m grid cells were above 10.9 ppt, the lifetime exposure concentration corresponding to 100-in-one million excess cancer risk (1 × 10-4). A small subset (3.3%) were above 109 ppt (1000-in-one million cancer risk, 1 × 10-3); these tended to be near EtO-emitting facilities, though we observed plumes over 10 km from the nearest facilities. Many plumes were highly correlated with other measured gases, indicating potential emission sources, and a subset was measured simultaneously with a second commercial analyzer, showing good agreement. We estimated EtO for 13 census tracts, all of which were higher than EPA estimates (median difference of 21.3 ppt). Our findings provide important information about EtO concentrations and potential exposure risks in a key industrial region and advance the application of EtO analytical methods for ambient sampling and mobile monitoring for air toxics.

Impact of commissural calcification on clinical outcome of percutaneous balloon mitral valvuloplasty; a retrospective cohort study of 876 patients.

BACKGROUND: Percutaneous balloon mitral valvuloplasty (PBMV) is the ACC/AHA class I recommendation for treating symptomatic rheumatic mitral stenosis with suitable valve morphology, less than moderate MR and absence of left atrium clot. The mitral valve restenosis and significant mitral regurgitation (MR) are known adverse outcomes of PBMV. This study aimed to evaluate the outcomes of PBMV in patients with severe mitral stenosis and the effect of Commissural Calcification (CC) on the outcomes. METHODS: In this single-center retrospective cohort study, 876 patients who underwent PBMV were categorized into three groups based on their Wilkins score (Group I: score ≤ 8, Group II: score 9-10, and Group III: score 11-12). Patients were evaluated before, early after PBMV and at 6- and 24-month follow-ups. Main clinical outcomes were defined as significant restenosis and or symptomatic significant MR (moderate to severe and severe MR) or candidate for mitral valve replacement (MVR). The outcomes were compared between patients with and without CC. RESULTS: A total of 876 patients with mean age 46.4 ± 12.3 years (81.0% females) were categorized based on Wilkins score. 333 (38.0%) were in Group I, 501 (57.2%) were in Group II, and 42 (4.8%) were in Group III. CC was present in 175 (20.0%) of the patients, among whom 95 (54.3%) had calcification of the anterolateral commissure, 64 (36.6%) had calcification of the posteromedial commissure, and in 16 (9.1%) patients both commissures were calcified. There was a significant difference in Wilkins score between patients with and without CC (P < 0.001). CC was associated with higher odds of significant symptomatic MR at early and mid-term follow up (OR: 1.69, 95%CI 1.19-2.41, P = 0.003; and OR: 3.90, 95%CI 2.61-5.83, P < 0.001, respectively), but not with restenosis (P = 0.128). Wilkins Groups II and III did not show higher odds of significant symptomatic MR compared to Group I at early (II: P = 0.784; III: P = 0.098) and mid-term follow up (II: P = 0.216; III: P = 0.227). Patients in Wilkins Group II had higher odds of restenosis compared to Group I (OR: 2.96,95%CI: 1.35-6.27, P = 0.007). CONCLUSION: Commissural calcification (CC) is an independent predictor of the significant symptomatic MR (an important determinant of adverse outcome) following PBMV in the early and mid-term follow-up. Mitral valve restenosis occurs more in patients with higher Wilkins score compared to group I with score ≤ 8. Combined Wilkins score and CC should be considered for patient suitability for PBMV.