Molecular Taxonomy of Myelodysplastic Syndromes and its Clinical Implications.

Myelodysplastic syndromes/neoplasms (MDS) are clonal hematologic disorders characterized by morphologic abnormalities of myeloid cells and peripheral cytopenias. While genetic abnormalities underlie the pathogenesis of these disorders and their heterogeneity, current classifications of MDS rely predominantly on morphology. We performed genomic profiling of 3,233 patients with MDS or related disorders to delineate molecular subtypes and define their clinical implications. Gene mutations, copy-number alterations (CNAs), and copy-neutral loss of heterozygosity (cnLOH) were derived from targeted sequencing of a 152-gene panel, with abnormalities identified in 91, 43, and 11% of patients, respectively. We characterized 16 molecular groups, encompassing 86% of patients, using information from 21 genes, 6 cytogenetic events, and LOH at the TP53 and TET2 loci. Two residual groups defined by negative findings (molecularly not-otherwise specified, absence of recurrent drivers) comprised 14% of patients. The groups varied in size from 0.5% to 14% of patients and were associated with distinct clinical phenotypes and outcomes. The median bone marrow blast percentage across groups ranged from 1.5 to 10%, and the median overall survival from 0.9 to 8.2 years. We validated 5 well-characterized entities, added further evidence to support 3 previously reported subsets, and described 8 novel groups. The prognostic influence of bone marrow blasts depended on the genetic subtypes. Within genetic subgroups, therapy-related MDS and myelodysplastic/myeloproliferative neoplasms (MDS/MPN) had comparable clinical and outcome profiles to primary MDS. In conclusion, genetically-derived subgroups of MDS are clinically relevant and may inform future classification schemas and translational therapeutic research.

Molecular and clinical presentation of UBA1-mutated myelodysplastic syndromes.

Mutations in UBA1, which are disease-defining for VEXAS syndrome, have been reported in patients diagnosed with myelodysplastic syndromes (MDS). Here, we define the prevalence and clinical associations of UBA1 mutations in a representative cohort of patients with MDS. Digital droplet PCR profiling of a selected cohort of 375 male patients lacking MDS disease-defining mutations or established WHO disease classification identified 28 patients (7%) with UBA1 p.M41T/V/L mutations. Using targeted sequencing of UBA1 in a representative MDS cohort (n=2,027), we identified an additional 27 variants in 26 patients (1%), which we classified as likely/pathogenic (n=12) and unknown significance (n=15). Among the total 40 patients with likely/pathogenic variants (2%), all were male and 63% were classified by WHO2016 as MDS-MLD/SLD. Patients had a median of one additional myeloid gene mutation, often in TET2 (n=12), DNMT3A (n=10), ASXL1 (n=3), or SF3B1 (n=3). Retrospective clinical review where possible showed that 83% (28/34) UBA1-mutant cases had VEXAS-associated diagnoses or inflammatory clinical presentation. The prevalence of UBA1-mutations in MDS patients argues for systematic screening for UBA1 in the management of MDS.

Refining risk stratification in paediatric B-acute lymphoblastic leukaemia: Combining IKZF1plus and Day 15 MRD positivity.

This study investigates the potential utility of IKZF1 deletion as an additional high-risk marker for paediatric acute lymphoblastic leukaemia (ALL). The prognostic impact of IKZF1 status, in conjunction with minimal/measurable residual disease (MRD), was evaluated within the MRD-guided TPOG-ALL-2013 protocol using 412 newly diagnosed B-ALL patients aged 1-18. IKZF1 status was determined using multiplex ligation-dependent probe amplification. IKZF1 deletions, when co-occurring with CDKN2A, CDKN2B, PAX5 or PAR1 region deletions in the absence of ERG deletions, were termed IKZF1plus. Both IKZF1 deletion (14.6%) and IKZF1plus (7.8%) independently predicted poorer outcomes in B-ALL. IKZF1plus was observed in 4.1% of Philadelphia-negative ALL, with a significantly lower 5-year event-free survival (53.9%) compared to IKZF1 deletion alone (83.8%) and wild-type IKZF1 (91.3%) (p < 0.0001). Among patients with Day 15 MRD ≥0.01%, provisional high-risk patients with IKZF1plus exhibited the worst outcomes in event-free survival (42.0%), relapse-free survival (48.0%) and overall survival (72.7%) compared to other groups (p < 0.0001). Integration of IKZF1plus and positive Day 15 MRD identified a subgroup of Philadelphia-negative B-ALL with a 50% risk of relapse. This study highlights the importance of assessing IKZF1plus alongside Day 15 MRD positivity to identify patients at increased risk of adverse outcomes, potentially minimizing overtreatment.

Systematic Reviews and Meta-analyses of the Procedure-specific Risks of Thrombosis and Bleeding in General Abdominal, Colorectal, Upper Gastrointestinal, and Hepatopancreatobiliary Surgery.

OBJECTIVE: To provide procedure-specific estimates of symptomatic venous thromboembolism (VTE) and major bleeding after abdominal surgery. BACKGROUND: The use of pharmacological thromboprophylaxis represents a trade-off that depends on VTE and bleeding risks that vary between procedures; their magnitude remains uncertain. METHODS: We identified observational studies reporting procedure-specific risks of symptomatic VTE or major bleeding after abdominal surgery, adjusted the reported estimates for thromboprophylaxis and length of follow-up, and estimated cumulative incidence at 4 weeks postsurgery, stratified by VTE risk groups, and rated evidence certainty. RESULTS: After eligibility screening, 285 studies (8,048,635 patients) reporting on 40 general abdominal, 36 colorectal, 15 upper gastrointestinal, and 24 hepatopancreatobiliary surgery procedures proved eligible. Evidence certainty proved generally moderate or low for VTE and low or very low for bleeding requiring reintervention. The risk of VTE varied substantially among procedures: in general abdominal surgery from a median of <0.1% in laparoscopic cholecystectomy to a median of 3.7% in open small bowel resection, in colorectal from 0.3% in minimally invasive sigmoid colectomy to 10.0% in emergency open total proctocolectomy, and in upper gastrointestinal/hepatopancreatobiliary from 0.2% in laparoscopic sleeve gastrectomy to 6.8% in open distal pancreatectomy for cancer. CONCLUSIONS: VTE thromboprophylaxis provides net benefit through VTE reduction with a small increase in bleeding in some procedures (eg, open colectomy and open pancreaticoduodenectomy), whereas the opposite is true in others (eg, laparoscopic cholecystectomy and elective groin hernia repairs). In many procedures, thromboembolism and bleeding risks are similar, and decisions depend on individual risk prediction and values and preferences regarding VTE and bleeding.

Low- or standard-dose edoxaban versus antiplatelet therapy for leaflet thrombus and cerebral thromboembolism after TAVR: A prespecified analysis of randomized ADAPT-TAVR trial.

BACKGROUND: The risks of leaflet thrombosis and the associated cerebral thromboembolism are unknown according to different anticoagulation dosing after transcatheter aortic valve replacement (TAVR). The aim was to evaluate the incidence of leaflet thrombosis and cerebral thromboembolism between low-dose (30 mg) or standard-dose (60 mg) edoxaban and dual antiplatelet therapy (DAPT) after TAVR. METHODS: In this prespecified subgroup analysis of the ADAPT-TAVR trial, the primary endpoint was the incidence of leaflet thrombosis on 4-dimensional computed tomography at 6-months. Key secondary endpoints were new cerebral lesions on brain magnetic resonance imaging and neurological and neurocognitive dysfunction. RESULTS: Of 229 patients enrolled in this study, 118 patients were DAPT group and 111 were edoxaban group (43 [39.1%] 60 mg vs 68 [61.3%] 30 mg). There was a significantly lower incidence of leaflet thrombosis in the standard-dose edoxaban group than in the DAPT group (2.4% vs 18.3%; odds ratio [OR] 0.11; 95% confidence interval [CI], 0.01-0.55; P = .03). However, no significant difference was observed between low-dose edoxaban and DAPT (15.0% vs 18.3%; OR 0.79; 95% CI, 0.32-1.81; P = .58). Irrespective of different antithrombotic regiments, the percentages of patients with new cerebral lesions on brain MRI and worsening neurological or neurocognitive function were not significantly different. CONCLUSIONS: In patients without an indication for anticoagulation after TAVR, the incidence of leaflet thrombosis was significantly lower with standard-dose edoxaban but not with low-dose edoxaban, as compared with DAPT. However, this differential effect of edoxaban on leaflet thrombosis was not associated with a reduction of new cerebral thromboembolism and neurological dysfunction.

Assessment of guidelines for bariatric and metabolic surgery: a systematic review and evaluation using appraisal of guidelines for research and evaluation II (AGREE II).

BACKGROUND: In recent years, multiple guidelines on bariatric and metabolic surgery were published, however, their quality remains unknown, leaving providers with uncertainty when using them to make perioperative decisions. This study aims to evaluate the quality of existing guidelines for perioperative bariatric surgery care. METHODS: A comprehensive search of MEDLINE and EMBASE were conducted from January 2010 to October 2022 for bariatric clinical practice guidelines. Guideline evaluation was carried out using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) framework. RESULTS: The initial search yielded 1483 citations, of which, 26 were included in final analysis. The overall median domain scores for guidelines were: (1) scope and purpose: 87.5% (IQR: 57-94%), (2) stakeholder involvement: 49% (IQR: 40-64%), (3) rigor of development: 42.5% (IQR: 22-68%), (4) clarity of presentation: 85% (IQR: 81-90%), (5) applicability: 6% (IQR: 3-16%), (6) editorial independence: 50% (IQR: 48-67%), (7) overall impressions: 48% (IQR: 33-67%). Only six guidelines achieved an overall score >70%. CONCLUSIONS: Bariatric surgery guidelines effectively outlined their aim and presented recommendations. However, many did not adequately seek patient input, state search criteria, use evidence rating tools, and consider resource implications. Future guidelines should reference the AGREE II framework in study design.

Diverse geotropic responses in the orchid family.

In epiphytes, aerial roots are important to combat water-deficient, nutrient-poor, and high-irradiance microhabitats. However, whether aerial roots can respond to gravity and whether auxin plays a role in regulating aerial root development remain open-ended questions. Here, we investigated the gravitropic response of the epiphytic orchid Phalaenopsis aphrodite. Our data showed that aerial roots of P. aphrodite failed to respond to gravity, and this was correlated with a lack of starch granules/statolith sedimentation in the roots and the absence of the auxin efflux carrier PIN2 gene. Using an established auxin reporter, we discovered that auxin maximum was absent in the quiescent center of aerial roots of P. aphrodite. Also, gravity failed to trigger auxin redistribution in the root caps. Hence, loss of gravity sensing and gravity-dependent auxin redistribution may be the genetic factors contributing to aerial root development. Moreover, the architectural and functional innovations that achieve fast gravitropism in the flowering plants appear to be lost in both terrestrial and epiphytic orchids, but are present in the early diverged orchid subfamilies. Taken together, our findings provide physiological and molecular evidence to support the notion that epiphytic orchids lack gravitropism and suggest diverse geotropic responses in the orchid family.

Assessing the robustness of positive vascular surgery randomized controlled trials using their fragility index.

OBJECTIVE: The fragility index (FI) measures the robustness of statistically significant findings in randomized controlled trials (RCTs) by quantifying the minimum number of event conversions required to reverse a dichotomous outcome's statistical significance. In vascular surgery, many clinical guidelines and critical decision-making points are informed by a handful of key RCTs, especially regarding open surgical versus endovascular treatment. The objective of this study is to evaluate the FI of RCTs with statistically significant primary outcomes that compared open vs endovascular surgery in vascular surgery. METHODS: In this meta-epidemiological study and systematic review, MEDLINE, Embase, and CENTRAL were searched for RCTs comparing open versus endovascular treatments for abdominal aortic aneurysms, carotid artery stenosis, and peripheral arterial disease to December 2022. RCTs with statistically significant primary outcomes were included. Data screening and extraction were conducted in duplicate. The FI was calculated by adding an event to the group with the smaller number of events while subtracting a nonevent to the same group until Fisher's exact test produced a nonstatistically significant result. The primary outcome was the FI and proportion of outcomes where the loss to follow-up was greater than the FI. The secondary outcomes assessed the relationship of the FI to disease state, presence of commercial funding, and study design. RESULTS: Overall, 5133 articles were captured in the initial search with 21 RCTs reporting 23 different primary outcomes being included in the final analysis. The median FI (first quartile, third quartile) was 3 (3, 20) with 16 outcomes (70%) reporting a loss to follow-up greater than its FI. Mann-Whitney U test revealed that commercially funded RCTs and composite outcomes had greater FIs (median, 20.0 [5.5, 24.5] vs median, 3.0 [2.0, 5.5], P = .035; median, 21 [8, 38] vs median, 3.0 [2.0, 8.5], P = .01, respectively). The FI did not vary between disease states (P = .285) or between index and follow-up trials (P = .147). There were significant correlations between the FI and P values (Pearson r = 0.90; 95% confidence interval, 0.77-0.96), and the number of events (r = 0.82; 95% confidence interval, 0.48-0.97). CONCLUSIONS: A small number of event conversions (median, 3) are needed to alter the statistical significance of primary outcomes in vascular surgery RCTs evaluating open surgical and endovascular treatments. Most studies had loss to follow-up greater than its FI, which can call into question trial results, and commercially funded studies had a greater FI. The FI and these findings should be considered in future trial design in vascular surgery.

Mode of carbon gain and fungal associations of Neuwiedia malipoensis within the evolutionary early diverging orchid subfamily Apostasioideae.

BACKGROUND AND AIMS: The earliest diverging orchid lineage Apostasioideae consists only of two genera: Apostasia and Neuwiedia. Previous report of Apostasia nipponica indicated a symbiotic association with an ectomycorrhiza-forming Ceratobasidiaceae clade and partial utilization of fungal carbon during the adult stage. However, the trophic strategy of Neuwiedia throughout its development remains unidentified. To further improve our understanding of mycoheterotrophy in the Apostasioideae, this study focused on Neuwiedia malipoensis examining both the mycorrhizal association and the physiological ecology of this orchid species across various development stages. METHODS: We identified the major mycorrhizal fungi of N. malipoensis protocorm, leafy seedling and adult stages using molecular barcoding. To reveal nutritional resources utilized by N. malipoensis, we compared stable isotope natural abundance (δ13C, δ15N, δ2H, δ18O) of different developmental stages to autotrophic reference plants. KEY RESULTS: Protocorms exhibited an association with saprotrophic Ceratobasidiaceae rather than ectomycorrhiza-forming Ceratobasidiaceae and 13C signature was characteristic of their fully mycoheterotrophic nutrition.Seedlings and adults predominantly associated with saprotrophic fungi belonging to the Tulasnellaceae. While 13C and 2H stable isotope data revealed partial mycoheterotrophy of seedlings, it is unclear to what extent the fungal carbon supply is reduced in adult N. malipoensis. However, the 15N enrichment of mature N. malipoensis suggests partially mycoheterotrophic nutrition.Our data indicated a transition in mycorrhizal partners during ontogenetic development with decreasing dependency of N. malipoensis on fungal nitrogen and carbon. CONCLUSIONS: The divergence in mycorrhizal partners between N. malipoensis and A. nipponica indicates different resource acquisition strategies and allows for various habitat options in the earliest diverging orchid lineage Apostasioideae. While A. nipponica relies on the heterotrophic C gain from its ectomycorrhizal fungal partner and thus on forest habitats, N. malipoensis rather relies on own photosynthetic C gain as adult allowing it to establish in habitats as widely distributed as those where Rhizoctonia fungi occur.

Plasma fatty acid esters of hydroxy fatty acids and surrogate fatty acid esters of hydroxy fatty acids hydrolysis activity in children with or without obesity and in adults with or without coronary artery disease.

AIM: Fatty acid esters of hydroxy fatty acids (FAHFA) are a class of bioactive lipids with anti-inflammatory, antidiabetic and cardioprotective properties. FAHFA hydrolysis into its fatty acid (FA) and hydroxy fatty acid (HFA) constituents can affect the bioavailability of FAHFA and its subsequent biological effects. We aimed to investigate FAHFA levels and FAHFA hydrolysis activity in children with or without obesity, and in adults with or without coronary artery disease (CAD). MATERIALS AND METHODS: Our study cohort included 20 children without obesity, 40 children with obesity, 10 adults without CAD and 28 adults with CAD. We quantitated plasma levels of four families of FAHFA [palmitic acid hydroxy stearic acid (PAHSA), palmitoleic acid hydroxy stearic acid (POHSA), oleic acid hydroxy stearic acid (OAHSA), stearic acid hydroxy stearic acid] and their corresponding FA and HFA constituents using liquid chromatography-tandem mass spectrometry analysis. Surrogate FAHFA hydrolysis activity was estimated as the FA/FAHFA or HFA/FAHFA ratio. RESULTS: Children with obesity had lower plasma PAHSA (p = .001), OAHSA (p = .006) and total FAHFA (p = .011) levels, and higher surrogate FAHFA hydrolysis activity represented by PA/PAHSA (p = .040) and HSA/OAHSA (p = .025) compared with children without obesity. Adults with CAD and a history of myocardial infarction (MI) had lower POHSA levels (p = .026) and higher PA/PAHSA (p = .041), POA/POHSA (p = .003) and HSA/POHSA (p = .038) compared with those without MI. CONCLUSION: Altered FAHFA metabolism is associated with obesity and MI, and inhibition of FAHFA hydrolysis should be studied further as a possible therapeutic strategy in obesity and MI.

The cross-sectional and prospective associations of parental practices and environmental factors with 24-hour movement behaviours among school-aged Asian children.

BACKGROUND: Parental practices and neighbourhood environmental factors may influence children's movement behaviours. We aimed to investigate the cross-sectional and prospective associations of parental practices and neighbourhood environmental factors with accelerometer-measured 24-hour movement behaviours (24 h-MBs) among school-aged children in Singapore. METHODS: The Growing Up in Singapore Towards healthy Outcomes (GUSTO) study collected information on dimensions of parental practices and neighbourhood environment at age 5.5 years. Confirmatory factor analyses were performed to generate latent variables and used to compute overall parental practices [involvement in PA + support for PA + control of screen viewing context] and environmental scores [facilities for active play + active mobility facilitators + barriers*-1]. Children wore an accelerometer on their non-dominant wrist for seven consecutive days at ages 5.5 and 8 years. The R-package GGIR 2.6 was used to derive moderate-to-vigorous-intensity physical activity (MVPA), light-intensity physical activity (LPA), inactivity, and total-sleep (napping+night sleep) minutes per day. Associations were determined using compositional data analysis with multivariate linear regression models, taking into account potential confounders. RESULTS: Among 425 children (48% girls, 59% Chinese), higher parental involvement in PA, parental support for PA and overall parental practices were associated with 24 h-MBs at ages 5.5 and 8 years, specifically with greater time spent in MVPA and less time being inactive relative to the remaining movement behaviours. The corresponding mean changes in the overall 24 h-MB for increasing parental practices from lowest to highest scores (- 2 to + 2 z-scores) indicated potential increases of up to 15-minutes in MVPA, 20-minutes in LPA, 5-minutes in sleep duration, and a reduction of 40-minutes in inactivity at age 5.5 years. At age 8 years, this could translate to approximately 15-minutes more of MVPA, 20-minutes more of LPA, a 20-minute reduction in sleep duration, and a 20-minute reduction in inactivity. Parental control of screen viewing contexts and neighbourhood environmental factors were not associated with 24 h-MBs. CONCLUSIONS: Parental practices but not environmental factors were associated with higher MVPA and lower inactivity among Singaporean children, even at a later age. Further research may provide insights that support development of targeted public health strategies to promote healthier movement behaviours among children. STUDY REGISTRATION: This study was registered on 4th August 2010 and is available online at ClinicalTrials.gov: NCT01174875.

Fragility of Statistically Significant Outcomes in Colonic Diverticular Disease Randomized Trials: A Systematic Review.

BACKGROUND: The p value has been criticized as an oversimplified determination of whether a treatment effect exists. One alternative is the fragility index. It is a representation of the minimum number of nonevents that would need to be converted to events to increase the p value above 0.05. OBJECTIVE: To determine the fragility index of randomized controlled trials assessing the efficacy of interventions for patients with diverticular disease since 2010 to assess the robustness of current evidence. DESIGN: MEDLINE, Embase, and Cochrane Central Register of Controlled Trials were searched from inception to August 2022. SETTINGS: Articles were eligible for inclusion if they were randomized trials conducted between 2010 and 2022 with parallel, superiority designs evaluating interventions in patients with diverticular disease. Only randomized trials with dichotomous primary outcomes with an associated p value of <0.05 were considered for inclusion. PARTICIPANTS: Any surgical or medical intervention for patients with diverticular disease. MAIN OUTCOME MEASURES: The fragility index was determined by adding events and subtracting nonevents from the groups with the smaller number of events. Events were added until the p value exceeded 0.05. The smallest number of events required was considered the fragility index. RESULTS: After screening 1271 citations, 15 randomized trials met the inclusion criteria. Nine of the studies evaluated surgical interventions and 6 evaluated medical interventions. The mean number of patients randomly assigned and lost to follow-up per randomized controlled trial was 92 (SD 35.3) and 9 (SD 11.4), respectively. The median fragility index was 1 (range, 0-5). The fragility indices for the included studies did not correlate significantly with any study characteristics. LIMITATIONS: Small sample, heterogeneity, and lack of inclusion of studies with continuous outcomes. CONCLUSIONS: The randomized trials evaluating surgical and medical interventions for diverticular disease are not robust. Changing a single-outcome event in most studies was sufficient to make a statistically significant study finding not significant. See Video Abstract . FRAGILIDAD DE LOS RESULTADOS ESTADSTICAMENTE SIGNIFICATIVOS EN ENSAYOS ALEATORIOS DE ENFERMEDAD DIVERTICULAR DEL COLON UNA REVISIN SISTEMTICA: ANTECEDENTES:El valor p ha sido criticado por una determinación demasiado simplificada de si existe un efecto del tratamiento. Una alternativa es el Índice de Fragilidad. Es una representación del número mínimo de no eventos que deberían convertirse en eventos para aumentar el valor p por encima de 0,05.OBJETIVO:Determinar el IF de ensayos controlados aleatorios que evalúan la eficacia de las intervenciones para pacientes con enfermedad diverticular desde 2010 para evaluar la solidez de la evidencia actual.FUENTES DE DATOS:Se realizaron búsquedas en MEDLINE, Embase y CENTRAL desde el inicio hasta agosto de 2022.SELECCIÓN DE ESTUDIOS:Los artículos eran elegibles para su inclusión si eran ensayos aleatorizados realizados entre 2010 y 2022 con diseños paralelos de superioridad que evaluaran intervenciones en pacientes con enfermedad diverticular. Sólo se consideraron para su inclusión los ensayos aleatorizados con resultados primarios dicotómicos con un valor de p asociado menor que 0,05.INTERVENCIÓNES:Cualquier intervención quirúrgica o médica para pacientes con enfermedad diverticular.PRINCIPALES MEDIDAS DE VALORACIÓN:El índice de fragilidad se determinó sumando eventos y restando no eventos de los grupos con el menor número de eventos. Se agregaron eventos hasta que el valor p superó 0,05. El menor número de eventos requeridos se consideró índice de fragilidad.RESULTADOS:Después de examinar 1271 citas, 15 ensayos aleatorios cumplieron los criterios de inclusión. Nueve de los estudios evaluaron intervenciones quirúrgicas y seis evaluaron intervenciones médicas. El número medio de pacientes aleatorizados y perdidos durante el seguimiento por ECA fue 92 (DE 35,3) y 9 (DE 11,4), respectivamente. La mediana del índice de fragilidad fue 1 (rango: 0-5). Los índices de fragilidad de los estudios incluidos no se correlacionaron significativamente con ninguna característica del estudio.LIMITACIONES:Muestra pequeña, heterogeneidad y falta de inclusión de estudios con resultados continuos.CONCLUSIONES:Los ensayos aleatorios que evalúan las intervenciones quirúrgicas y médicas para la enfermedad diverticular no son sólidos. Cambiar un solo evento de resultado en la mayoría de los estudios fue suficiente para que un hallazgo estadísticamente significativo del estudio no fuera significativo. (Traducción- Dr. Ingrid Melo ).

Assessing the Modified Frailty Index and Post-Operative Outcomes in Adhesive Small Bowel Obstruction: A Retrospective Cohort Study.

INTRODUCTION: Studies identifying predictors of postoperative outcomes in adhesive small bowel obstruction are limited. This study investigates the efficacy of the modified frailty index (mFI)to predict postoperative morbidity and mortality among patients undergoing surgery for adhesive small bowel obstruction. METHODS: A multicentre retrospective cohort study including patients undergoing surgery for adhesive small bowel obstruction after failed trial of nonoperative management between January 2015 and December 2020 was performed. Impact of frailty status using the mFI, stratified as frail (≥0.27) and robust (<0.27), on postoperative morbidity, mortality, length of stay, and discharge destination was evaluated using multiple logistic regression. RESULTS: Ninety-two robust patients (mean age 62.4 y, 68% female) and 41 frail patients (mean age 81.7 y, 63% female) were included. On simple stratification, frail patients had significantly increased 30-d morbidity (overall morbidity 80% versus 49%) and need for higher level of care on discharge (41% versus 9%). However, on multiple regression, functional dependence but not the mFI, was independently associated with worse 30-d overall morbidity (odds ratio [OR] 3.97, confidence interval [CI] 1.29-12.19) and lower likelihood of returning to preoperative disposition (OR 0.21, CI 0.05-0.91). The delay in operation beyond 5 d was independently associated with worse 30-d outcomes including overall morbidity and mortality (OR 7.54, CI 2.13-26.73) and decreased return to preoperative disposition (OR 0.14, CI 0.04-0.56). CONCLUSIONS: The mFI, although promising, was not independently predictive of outcomes following surgery for adhesive small bowel obstruction. Further adequately powered studies are required.

Short-term postoperative outcomes for obese versus non-obese inflammatory bowel disease patients undergoing bowel resection: a propensity score matched analysis.

PURPOSE: Up to 40% of patients with inflammatory bowel disease (IBD) are obese. Obesity is a well-known risk factor for increased perioperative morbidity, but this risk has never been quantified in IBD patients undergoing abdominal surgery using the United States National Inpatient Sample (NIS) database. This study aims to compare postoperative morbidity between obese and non-obese patients undergoing bowel resection for IBD using recent NIS data. METHODS: Adult patients who underwent bowel resection for IBD from 2015 to 2019 were identified in the NIS using ICD-10-CM coding. Patients were stratified into obese (BMI > 30 kg/m2) and non-obese groups, then propensity score matched (PSM) for demographic, operative, and hospital characteristics. The primary outcome was postoperative in-hospital morbidity. Secondary outcomes included postoperative in-hospital mortality, system-specific postoperative complications, total admission healthcare costs, and length of stay (LOS). Univariable and multivariable regressions were utilized. RESULTS: Overall, 6601 non-obese patients and 671 obese patients were identified. The PSM cohort included 659 patients per group. Obese patients had significantly increased odds of experiencing postoperative in-hospital morbidity (aOR 1.50, 95% CI 1.10-2.03, p = 0.010) compared to non-obese patients. Specifically, obese patients experienced increased gastrointestinal complications (aOR 1.49, 95% CI 1.00-2.24, p = 0.050), and genitourinary complications (aOR 1.71, 95% CI 1.12-2.61, p = 0.013). There were no differences in total admission healthcare costs (MD - $2256.32, 95% CI - 19,144.54-14,631.9, p = 0.79) or LOS (MD 0.16 days, 95% CI - 0.93-1.27, p = 0.77). CONCLUSIONS: Obese IBD patients are at greater risk of postoperative in-hospital morbidity than non-obese IBD patients. This supports targeted preoperative weight loss protocols for IBD patients to optimize surgical outcomes.

Frailty in inflammatory bowel disease: analysis of the National Inpatient Sample 2015-2019.

AIM: Preoperative frailty has been associated with adverse postoperative outcomes in various populations, but of its use in patients with inflammatory bowel disease (IBD) remains sparse. The present study aimed to characterize the impact of frailty, as measured by the modified frailty index (mFI), on postoperative clinical and resource utilization outcomes in patients with IBD. METHODS: This retrospective population-based cohort study assessed patients from the National Inpatient Sample database from 1 September 2015 to 31 December 2019. Corresponding International Classification of Diseases 10th Revision Clinical Modification codes were used to identify adult patients (>18 years of age) with IBD, undergoing either small bowel resection, colectomy or proctectomy. Patient demographics and institutional data were collected for each patient to calculate the 11-point mFI. Patients were categorized as either frail or robust using a cut-off of 0.27. Primary outcomes were postoperative in-hospital morbidity and mortality, whilst secondary outcomes included system-specific morbidity, length of stay, in-hospital healthcare costs and discharge disposition. Logistic and linear regression models were used for primary and secondary outcomes. RESULTS: Overall, 7144 patients with IBD undergoing small bowel resection, colectomy or proctectomy were identified, 337 of whom were classified as frail (i.e., mFI < 0.27). Frail patients were more likely to be women, older, have lower income and a greater number of comorbidities. After adjusting for relevant covariates, frail patients were at greater odds of in-hospital mortality (adjusted odds ratio [aOR] 5.42, 95% CI 2.31-12.77, P < 0.001), overall morbidity (aOR 1.72, 95% CI 1.30-2.28, P < 0.001), increased length of stay (adjusted mean difference 1.3 days, 95% CI 0.09-2.50, P = 0.035) and less likely to be discharged to home (aOR 0.59, 95% CI 0.45-0.77, P < 0.001) compared to their robust counterparts. CONCLUSIONS: Frail IBD patients are at greater risk of postoperative mortality and morbidity, and reduced likelihood of discharge to home, following surgery. This has implications for clinicians designing care pathways for IBD patients following surgery.

The impact of operative approach for obese colorectal cancer patients: analysis of the National Inpatient Sample 2015-2019.

AIM: Obesity is a well-established risk factor for the development of colorectal cancer. As such, patients undergoing surgery for colorectal cancer have increasingly higher body mass indices (BMIs). The advances in minimally invasive surgical techniques in recent years have helped surgeons circumvent some of the challenges associated with operating in the setting of obesity. While previous studies suggest that laparoscopy improves outcomes compared with open surgery in obese patients, this has never been established at the population level. Therefore, we designed a retrospective database study using the National Inpatient Sample (NIS) with the aim of comparing laparoscopic with open approaches for obese patients undergoing surgery for colorectal cancer. METHOD: A retrospective analysis of the NIS from 2015 to 2019 was conducted including patients with a BMI of greater than 30 kg/m2 undergoing surgery for colorectal cancer. The primary outcomes were postoperative in-hospital morbidity and mortality. Secondary outcomes included postoperative system-specific complications, total admission healthcare cost and length of stay (LOS). Multivariable logistic and linear regressions were utilized to compare the two operative approaches. RESULTS: A total of 4742 patients underwent open surgery and 3231 underwent laparoscopic surgery. We observed a significant decrease in overall postoperative morbidity [17.5% vs. 31.4%, adjusted odds ratio (aOR) 0.56, 95% confidence interval (CI) 0.50-0.64; p < 0.001], gastrointestinal morbidity (8.1% vs. 14.5%, aOR 0.59, 95% CI 0.50-0.69; p < 0.001) and genitourinary morbidity (10.1% vs. 18.6%, aOR 0.61, 95% CI 0.52-0.70; p < 0.001) with the use of laparoscopy. Postoperative LOS was 1.7 days shorter (95% CI 1.5-2.0, p < 0.001) and cost of admission was decreased by $9106 (95% CI $4638-$13 573, p < 0.001) with laparoscopy. CONCLUSION: Laparoscopic surgery for obese patients with colorectal cancer is associated with significantly decreased postoperative morbidity and improved healthcare resource utilization compared with open surgery. Laparoscopic approaches should be relied upon whenever feasible for these patients.

Financial toxicity among patients undergoing resectional surgery for inflammatory bowel disease in the United States.

AIM: Financial toxicity describes the financial burden and distress that patients experience due to medical treatment. Financial toxicity has yet to be characterized among patients with inflammatory bowel disease (IBD) undergoing surgical management of their disease. This study investigated the risk of financial toxicity associated with undergoing surgery for IBD. METHODS: This study used a retrospective analysis using the National Inpatient Sample from 2015 to 2019. Adult patients who underwent IBD-related surgery were identified using the International Classification of Diseases (10th Revision) diagnostic and procedure codes and stratified into privately insured and uninsured groups. The primary outcome was risk of financial toxicity, defined as hospital admission charges that constituted 40% or more of patient's post-subsistence income. Secondary outcomes included total hospital admission cost and predictors of financial toxicity. RESULTS: The analytical cohort consisted of 6412 privately insured and 3694 uninsured patients. Overall median hospital charges were $21 628 (interquartile range $14 758-$35 386). Risk of financial toxicity was 86.5% among uninsured patients and 0% among insured patients. Predictors of financial toxicity included emergency admission, being in the lowest residential income quartile and having ulcerative colitis (compared to Crohn's disease). Additional predictors were being of Black race or male sex. CONCLUSION: Financial toxicity is a serious consequence of IBD-related surgery among uninsured patients. Given the pervasive nature of this consequence, future steps to support uninsured patients receiving surgery, in particular emergency surgery, related to their IBD are needed to protect this group from financial risk.

Evaluating frailty using the modified frailty index for colonic diverticular disease surgery: analysis of the national inpatient sample 2015-2019.

BACKGROUND: Frailty has been associated with increased postoperative mortality and morbidity; however, the use of the modified frailty index (mFI-11) to assess patients undergoing surgery for diverticular disease has not been widely assessed. This paper aims to examine frailty, evaluated by mFI-11, to assess postoperative morbidity and mortality among patients undergoing operative intervention for colonic diverticular disease. METHODS: We used data from the Healthcare Cost and Utilization Project National Inpatient Sample (October 1, 2015-December 31, 2019). ICD-10-CM codes were utilized to identify a cohort of adult patients with a primary admission diagnosis of diverticulitis. mFI-11 items were adapted to correspond with ICD-10-CM codes. Patients were stratified into robust (mFI < 0.27) and frail (mFI ≥ 0.27) groups. Primary outcomes were in-hospital postoperative morbidity and mortality. Secondary outcomes included system-specific postoperative complications, length of stay (LOS), total admission cost, and discharge disposition. Multivariable regression models were fit. RESULTS: Of the 26,826 patients, there were 24,194 patients with mFI-11 < 0.27 (i.e., robust) and 2,632 patients with mFI-11 ≥ 0.27 (i.e., frail). Adjusted analysis showed significant increases in postoperative mortality (aOR 2.16, 95% CI 1.38-3.38, p = 0.001) and overall postoperative morbidity (aOR 1.84, 95% CI 1.65-2.06, p < 0.001). LOS was higher in the frail group (MD 1.78 days, 95% CI 1.46-2.11, p < 0.001) as well as total cost (MD $25,495.19, 95% CI $19,851.63-$31,138.75, p < 0.001). CONCLUSION: In the elective setting, a high mFI-11 (i.e., presence of the variables comprising the index) could alert clinicians to the possibility of implementing preoperative optimization strategies. In the emergent setting, a high mFI-11 may help guide prognostication for these vulnerable patients.

LONGITUDINAL CHANGES IN CHOROIDAL THICKNESS IN CHILDREN WITH A HISTORY OF PREMATURITY: An 18-Month Prospective Cohort Study.

PURPOSE: To evaluate choroidal changes over time in school-age children with a history of prematurity. METHODS: A study of 416 eyes of 208 eligible participants, including 88, 190, 36, 56, and 46 eyes in the full-term control, preterm, spontaneously regressed retinopathy of prematurity, intravitreal bevacizumab (injection of bevacizumab)-treated retinopathy of prematurity, and laser-treated retinopathy of prematurity groups, respectively, were enrolled in this study. The choroidal thickness was measured 4 times at 6-month intervals using optical coherence tomography. RESULTS: Of all the groups, the laser-treated children had the thinnest choroid compared with full-term children (-52.3 µ m, P = 0.04). Preterm children exhibited greater attenuation in choroidal thickness over time than did full-term children (-6.3 ± 26.9 and -1.1 ± 12.8 µ m/year, P = 0.03), whereas no difference was observed between injection of bevacizumab and laser treatments (-4.6 ± 18.9 and -2.0 ± 15.7 µ m/year, P = 0.46). In all groups, the changes in axial length were negatively associated with the changes in choroidal thickness (all P < 0.05). CONCLUSION: A greater attenuation in choroid thickness over time was observed in preterm children than in full-term children, but this attenuation did not differ between injection of bevacizumab and laser treatments. Axial elongation was associated with choroidal thinning in school-age children.

YouTube as a source of education in perioperative anesthesia for patients and trainees: a systematic review.

BACKGROUND: Online video sharing platforms like YouTube (Google LLC, San Bruno, CA, USA) have become a substantial source of health information. We sought to conduct a systematic review of studies assessing the overall quality of perioperative anesthesia videos on YouTube. METHODS: We searched Embase, MEDLINE, and Ovid for articles published from database inception to 1 May 2023. We included primary studies evaluating YouTube videos as a source of information regarding perioperative anesthesia. We excluded studies not published in English and studies assessing acute or chronic pain. Studies were screened and data were extracted in duplicate by two reviewers. We appraised the quality of studies according to the social media framework published in the literature. We used descriptive statistics to report the results using mean, standard deviation, range, and n/total N (%). RESULTS: Among 8,908 citations, we identified 14 studies that examined 796 videos with 59.7 hr of content and 47.5 million views. Among the 14 studies that evaluated the video content quality, 17 different quality assessment tools were used, only three of which were externally validated (Global Quality Score, modified DISCERN score, and JAMA score). Per global assessment rating of video quality, 11/13 (85%) studies concluded the overall video quality as poor. CONCLUSIONS: Overall, the educational content quality of YouTube videos evaluated in the literature accessible as an educational resource regarding perioperative anesthesia was poor. While these videos are in demand, their impact on patient and trainee education remains unclear. A standardized methodology for evaluating online videos is merited to improve future reporting. A peer-reviewed approach to online open-access videos is needed to support patient and trainee education in anesthesia. STUDY REGISTRATION: Open Science Framework ( https://osf.io/ajse9 ); first posted, 1 May 2023.

RéSUMé: CONTEXTE: Les plateformes de partage de vidéos en ligne comme YouTube (Google LLC, San Bruno, CA, États-Unis) sont devenues une source importante d'informations sur la santé. Nous avons cherché à réaliser une revue systématique des études évaluant la qualité globale des vidéos d'anesthésie périopératoire sur YouTube. MéTHODE: Nous avons recherché des articles dans Embase, MEDLINE et Ovid publiés depuis la création de ces bases de données jusqu'au 1er mai 2023. Nous avons inclus des études primaires évaluant les vidéos YouTube comme source d'information sur l'anesthésie périopératoire. Nous avons exclu les études publiées dans une langue autre que l'anglais et les études évaluant la douleur aiguë ou chronique. Les études ont été examinées et les données ont été extraites en double par deux personnes. Nous avons évalué la qualité des études selon le cadre des médias sociaux publié dans la littérature. Nous avons utilisé des statistiques descriptives pour rapporter les résultats en utilisant la moyenne, l'écart type, la plage et n/total N (%). RéSULTATS: Parmi 8908 citations, nous avons identifié 14 études qui ont examiné 796 vidéos avec 59,7 heures de contenu et 47,5 millions de vues. Parmi les 14 études qui ont évalué la qualité du contenu vidéo, 17 outils d'évaluation de la qualité différents ont été utilisés, dont seulement trois ont été validés en externe (Score Global Quality, score DISCERN modifié et score JAMA). Selon l'évaluation globale de la qualité des vidéos, 11 études sur 13 (85 %) ont conclu que la qualité globale des vidéos était médiocre. CONCLUSION: Dans l'ensemble, la qualité du contenu éducatif des vidéos YouTube évaluées dans la littérature accessible en tant que ressource éducative concernant l'anesthésie périopératoire était médiocre. Bien que ces vidéos soient très demandées, leur impact sur la formation de la patientèle et des stagiaires reste incertain. Une méthodologie normalisée d'évaluation des vidéos en ligne est nécessaire pour améliorer les évaluations futures. Une approche évaluée par les pairs pour les vidéos en libre accès en ligne est nécessaire pour soutenir la formation de la patientèle et des stagiaires en anesthésie. ENREGISTREMENT DE L'éTUDE: Open Science Framework ( https://osf.io/ajse9 ); première publication le 1er mai 2023.