DIBH reduces right coronary artery and lung radiation dose in right breast cancer loco-regional radiotherapy.

To determine whether deep inspiratory breath-hold (DIBH) reduces dose to organs-at-risk (OAR), in particular the right coronary artery (RCA), in women with breast cancer requiring right-sided post-mastectomy radiotherapy (PMRT) including internal mammary chain (+IMC) radiotherapy (RT). Fourteen consecutive women requiring right-sided PMRT + IMC were retrospectively identified. Nodal delineation was in accordance with European Society for Radiology and Oncology (ESTRO) guidelines and tangential chest wall fields marked. Patients were planned with Anisotropic Analytical Algorithm using free-breathing (FB) and DIBH datasets. Dose was calculated using Acuros External Beam algorithm. FB and DIBH dose comparisons were analyzed for heart, RCA and right lung, as were chest wall and IMC planning target volumes (PTVs). DIBH vs FB resulted in median decreases of: the RCA mean dose by 0.6Gray (Gy) (interquartile range (IQR) 0.1, 1.9) (p = 0.002), RCA max dose by 1.8Gy (IQR 0.8, 6.1) (p = 0.002), and V5Gy by 2.9% (IQR 0.0, 37.2) (p = 0.016). RCA data indicated no statistically significant dosimetric reduction ≥10Gy. A median reduction of 1.7Gy (c -0.0, 7.1) (p = 0.019) in maximum heart dose was recorded with DIBH vs FB; no significant difference was observed in other heart and left anterior descending coronary artery parameters. The median reduction in right lung mean dose was 2.8Gy for DIBH vs FB plans (IQR 1.6, 3.6) (p = 0.001); significant median reductions of V5Gy, V20Gy, and V30Gy were all achieved with DIBH. Chest wall PTV coverage did not significantly differ between DIBH and FB plans; IMC dosimetric coverage improved with use of DIBH (V47.5Gy, V45Gy, V42Gy). DIBH reduced OAR dose in right-sided PMRT + IMC patients. A novel finding was that DIBH decreased RCA dose. Heart and right lung dose were also decreased with DIBH, whilst optimally dosed PTVs were maintained.

A simplified algorithm to evaluate the risk of submucosal invasive cancer in large (≥20 mm) nonpedunculated colonic polyps.

BACKGROUND: Recognition of submucosal invasive cancer (SMIC) in large (≥20 mm) nonpedunculated colonic polyps (LNPCPs) informs selection of the optimal resection strategy. LNPCP location, morphology, and size influence the risk of SMIC; however, currently no meaningful application of this information has simplified the process to make it accessible and broadly applicable. We developed a decision-making algorithm to simplify the identification of LNPCP subtypes with increased risk of potential SMIC. METHODS: Patients referred for LNPCP resection from September 2008 to November 2022 were enrolled. LNPCPs with SMIC were identified from endoscopic resection specimens, lesion biopsies, or surgical outcomes. Decision tree analysis of lesion characteristics identified in multivariable analysis was used to create a hierarchical classification of SMIC prevalence. RESULTS: 2451 LNPCPs were analyzed: 1289 (52.6%) were flat, 1043 (42.6%) nodular, and 118 (4.8%) depressed. SMIC was confirmed in 273 of the LNPCPs (11.1%). It was associated with depressed and nodular vs. flat morphology (odds ratios [ORs] 35.7 [95%CI 22.6-56.5] and 3.5 [95%CI 2.6-4.9], respectively; P<0.001); rectosigmoid vs. proximal location (OR 3.2 [95%CI 2.5-4.1]; P<0.001); nongranular vs. granular appearance (OR 2.4 [95%CI 1.9-3.1]; P<0.001); and size (OR 1.12 per 10-mm increase [95%CI 1.05-1.19]; P<0.001). Decision tree analysis targeting SMIC identified eight terminal nodes: SMIC prevalence was 62% in depressed LNPCPs, 19% in nodular rectosigmoid LNPCPs, and 20% in nodular proximal colon nongranular LNPCPs. CONCLUSIONS: This decision-making algorithm simplifies identification of LNPCPs with an increased risk of potential SMIC. When combined with surface optical evaluation, it facilitates accurate lesion characterization and resection choices.

Left atrial shape as a marker of atrial myopathy in embolic stroke of undetermined source.

AIMS: Embolic Stroke of Undetermined Source (ESUS) results in significant morbidity. A left atrial (LA) myopathy is implicated in a proportion of these patients. We hypothesized that LA shape varies by cause of stroke (cardioembolic versus ESUS). METHODS AND RESULTS: 236 ischemic stroke, atrial fibrillation (AF) patients and controls were recruited prospectively. AF was classified as paroxysmal (PAF) or persistent AF (PersAF). Stroke patients comprised cardioembolic stroke (CE) secondary to AF and ESUS. There were 81 AF (47 PAF, 34 PersAF), 50 ESUS, 57 CE patients (subdivided into CE with PAF (CEpaf) and CE with PersAF (CEpers) and 48 controls. Echocardiographic parameters including LA volume, function, and shape/sphericity (3D LA-sphericity and 2D-derived LA-circularity, ellipticity, sphericity and eccentricity indices) were evaluated. Increased LA volume and sphericity with LA dysfunction was present in CE, AF and ESUS groups compared to controls. K-means cluster analysis demonstrated a spectrum of LA myopathy with controls at the lowest and CEpers and PersAF at the upper extremes, with ESUS, PAF and CEpaf being similar and falling between these extremes. After adjusting for age, sex and left ventricular (LV) and LA parameters, LA sphericity markers differentiated ESUS from controls (p < 0.01). CONCLUSIONS: Alterations in LA shape are present in ESUS, AF and CE patients, particularly increased spherical remodelling. The novel markers of LA sphericity proposed may identify LA myopathy in ESUS patients and potentially guide management for secondary prevention.

When less is more: lower esophageal sphincter-preserving peroral endoscopic myotomy is effective for non-achalasia esophageal motility disorders.

BACKGROUND: Non-achalasia esophageal motility disorders (NAEMDs), encompassing distal esophageal spasm (DES) and hypercontractile esophagus (HCE), are rare conditions. Peroral endoscopic myotomy (POEM) is a promising treatment option. In NAEMDs, unlike with achalasia, the lower esophageal sphincter (LES) functions normally, suggesting the potential of LES preservation during POEM. METHODS: This retrospective two-center observational study focused on patients undergoing LES-preserving POEM (LES-POEM) for NAEMD. Eckardt scores were assessed pre-POEM and at 6, 12, and 24 months post-POEM, with follow-up endoscopy at 6 months to evaluate for reflux esophagitis. Clinical success, defined as an Eckardt score ≤3, served as the primary outcome. RESULTS: 227 patients were recruited over 84 months until May 2021. Of these, 16 underwent LES-POEM for an NAEMD (9 with HCE and 7 with DES). The median pre-POEM Eckardt score was 6.0 (interquartile range [IQR] 5.0-7.0), which decreased to 1.0 (IQR 0.0-1.8; P<0.001) 6 months post-POEM. This was sustained at 24 months, with an Eckardt score of 1.0 (IQR 0.0-1.8; P<0.001). Two patients (12.5%) developed Los Angeles grade A or B esophagitis. CONCLUSIONS: LES-POEM for NAEMD demonstrates favorable clinical outcomes, with infrequent esophagitis and reintervention for LES dysfunction rarely required.

Influence of standard modifiable risk factors on ventricular tachycardia after myocardial infarction.

Background: Inducible ventricular tachycardia (VT) at electrophysiology study (EPS) predicts sudden cardiac death because of ventricular tachyarrhythmia, the single greatest cause of death within 2 years after myocardial infarction (MI). Objectives: We aimed to assess the association between standard modifiable risk factors (SMuRFs) and inducible VT at EPS early after MI. Methods: Consecutive patients with left ventricle ejection fraction ≤40% on days 3-5 after ST elevation MI (STEMI) who underwent EPS were prospectively recruited. Positive EPS was defined as induced sustained monomorphic VT cycle length ≥200 ms for ≥10 s or shorter if hemodynamically compromised. The primary outcome was inducibility of VT at EPS, and the secondary outcome was all-cause mortality on follow-up. Results: In 410 eligible patients undergoing EPS soon (median of 9 days) after STEMI, 126 had inducible VT. Ex-smokers experienced an increased risk of inducible VT [multivariable logistic regression adjusted odds ratio (OR) 2.0, p = 0.033] compared with current or never-smokers, with comparable risk. The presence of any SMuRFs apart from being a current smoker conferred an increased risk of inducible VT (adjusted OR 1.9, p = 0.043). Neither the number of SMuRFs nor the presence of any SMuRFs was associated with mortality at a median follow-up of 5.4 years. Conclusions: In patients with recent STEMI and impaired left ventricular function, the presence of any SMuRFs, apart from being a current smoker, conferred an increased risk of inducible VT at EPS. These results highlight the need to modify SMuRFs in this high-risk subset of patients.

Improving efficiency of fitting Cox proportional hazards models for time-to-event outcomes in genome-wide association studies (GWAS).

Summary: Technologies identifying single nucleotide polymorphisms (SNPs) in DNA sequencing yield an avalanche of data requiring analysis and interpretation. Standard methods may require many weeks of processing time. The use of statistical methods requiring data sorting, matrix inversions of a high-dimension and replication in subsets of the data on multiple outcomes exacerbate these times.A method which reduces the computational time in problems with time-to-event outcomes and hundreds of thousands/millions of SNPs using Cox-Snell residuals after fitting the Cox proportional hazards model (PH) to a fixed set of concomitant variables is proposed. This yields coefficients for SNP effect from a Cox-Snell adjusted Poisson model and shows a high concordance to the adjusted PH model.The method is illustrated with a sample of 10 000 SNPs from a genome-wide association study in a diabetic population. The gain in processing efficiency using the proposed method based on Poisson modelling can be as high as 62%. This could result in saving of over three weeks processing time if 5 million SNPs require analysis. The method involves only a single predictor variable (SNP), offering a simpler, computationally more stable approach to examining and identifying SNP patterns associated with the outcome(s) allowing for a faster development of genetic signatures. Use of deviance residuals from the PH model to screen SNPs demonstrates a large discordance rate at a 0.2% threshold of concordance. This rate is 15 times larger than that based on the Cox-Snell residuals from the Cox-Snell adjusted Poisson model. Availability and implementation: The method is simple to implement as the procedures are available in most statistical packges. The approach involves obtaining Cox-Snell residuals from a PH model, to a binary time-to-event outcome, for factors which need to be common when assessing each SNP. Each SNP is then fitted as a predictor to the outcome of interest using a Poisson model with the Cox-Snell as the exposure variable.

Impact of oral/dental disease burden on postoperative infective complications: a prospective cohort study.

OBJECTIVES: This prospective cohort study aimed to assess the association between dental disease burden and postoperative infective complications (POICs) in patients undergoing major surgical procedures under general anaesthesia. METHODS: Pre-surgical dental assessment was undertaken on patients planned for major surgery. Demographic and surgical variables including putative risk factors for POICs and POIC status were documented. The univariable association between POIC status and each factor was examined. Those variables associated at P value ≤ 0.2 were candidates for inclusion in multiple logistic regression models. Backward stepwise variable selection was used to identify the independent predictors for POIC in the best fitting logistic regression model. The area under the receiver operating curve (AUC) was used to quantify the model's global classification performance. RESULTS: Among the 285 patients, 49 patients (17.2%) had POICs. The independent predictors for POIC were expected length of hospital stay (4-6 days; odds ratio [OR] = 4.80, 95% confidence internal [CI]: 1.30-17.70, P = 0.018, 7-9 days; OR = 5.42, 95% CI: 1.51-19.41, P = 0.009, ≥ 10 days; OR = 28.80, 95% CI: 4.12-201.18, P < 0.001), four or more decayed teeth (OR = 6.03, 95% CI: 2.28-15.94, P < 0.001) and visible tongue plaque (OR = 3.21, 95% CI: 1.54-6.70, P = 0.002). The AUC was 0.78 (95% CI: 0.71-0.85) indicating good discrimination. A simple screening tool for POIC was developed. CONCLUSIONS/CLINICAL RELEVANCE: In addition to systemic/surgical factors, this study identified clinically detected decayed teeth and visible tongue plaque as independent predictors for POICs. Preoperative dental assessment/care might be beneficial to assess risk for POICs and improve postoperative outcomes.

Optimizing electrophysiology studies to prevent sudden cardiac death after myocardial infarction.

AIMS: This study assessed associations of minimum final extrastimulus coupling interval utilized within electrophysiology study (EPS) after myocardial infarction (MI) and possible site of origin of induced ventricular tachycardia (VT) with long-term occurrence of spontaneous ventricular tachyarrhythmia and long-term survival. METHODS AND RESULTS: This prospective study recruited consecutive patients with left ventricular ejection fraction (LVEF) ≤ 40% who underwent EPS days 3-5 after MI between 2004 and 2017. Positive EPS was defined as sustained monomorphic VT cycle length ≥200 ms for ≥10 s or shorter duration if haemodynamic compromise occurred. Each of the four extrastimuli was shortened by 10 ms at a time, until it failed to capture the ventricle (ventricular refractoriness) or induced ventricular tachyarrhythmia. Outcomes included spontaneous ventricular tachyarrhythmia occurrence and all-cause mortality. Shorter coupling interval length of final extrastimulus that induced VT was associated with higher risk of spontaneous ventricular tachyarrhythmia (P < 0.001). Significantly higher rates of spontaneous ventricular tachyarrhythmia (65.2% vs. 23.2%; P < 0.001) were observed for final coupling interval at EPS <200 ms vs. >200 ms. Right bundle branch block (RBBB) morphology of induced VT, with possible site of origin from the left ventricle, was associated with all-cause mortality [hazard ratio (HR) 3.2, P = 0.044] and a composite of spontaneous ventricular tachyarrhythmia recurrence or mortality (HR 1.8, P = 0.043). CONCLUSION: Ventricular tachycardia induced with shorter coupling intervals was associated with higher risk of spontaneous ventricular tachyarrhythymia on follow-up, indicating that the final extrastimulus coupling interval at EPS early after MI should be determined by ventricular refractoriness. Induced VT with possible origin from left ventricle was associated with increased risk of spontaneous ventricular tachyarrhythmia recurrence or death.

Cardiac "hypertrophy" phenotyping: differentiating aetiologies with increased left ventricular wall thickness on echocardiography.

Aims: Differentiating phenotypes of cardiac "hypertrophy" characterised by increased wall thickness on echocardiography is essential for management and prognostication. Transthoracic echocardiography is the most commonly used screening test for this purpose. We sought to identify echocardiographic markers that distinguish infiltrative and storage disorders that present with increased left ventricular (LV) wall thickness, namely, cardiac amyloidosis (CA) and Anderson-Fabry disease (AFD), from hypertensive heart disease (HHT). Methods: Patients were retrospectively recruited from Westmead Hospital, Sydney, and Princess Alexandra Hospital, Brisbane. LV structural, systolic, and diastolic function parameters, as well as global (LVGLS) and segmental longitudinal strains, were assessed. Previously reported echocardiographic parameters including relative apical sparing ratio (RAS), LV ejection fraction-to-strain ratio (EFSR), mass-to-strain ratio (MSR) and amyloidosis index (AMYLI) score (relative wall thickness × E/e') were evaluated. Results: A total of 209 patients {120 CA [58 transthyretin amyloidosis (ATTR) and 62 light-chain (AL) amyloidosis], 31 AFD and 58 HHT patients; mean age 64.1 ± 13.7 years, 75% male} comprised the study cohort. Echocardiographic measurements differed across the three groups, The LV mass index was higher in both CA {median 126.6 [interquartile range (IQR) 106.4-157.9 g/m2]} and AFD [median 134 (IQR 108.8-152.2 g/m2)] vs. HHT [median 92.7 (IQR 79.6-102.3 g/m2), p < 0.05]. LVGLS was lowest in CA [median 12.29 (IQR 10.33-15.56%)] followed by AFD [median 16.92 (IQR 14.14-18.78%)] then HHT [median 18.56 (IQR 17.51-19.97%), p < 0.05]. Diastolic function measurements including average e' and E/e' were most impaired in CA and least impaired in AFD. Indexed left atrial volume was highest in CA. EFSR and MSR differentiated secondary (CA + AFD) from HHT [receiver operating curve-area under the curve (ROC-AUC) of 0.80 and 0.91, respectively]. RAS and AMYLI score differentiated CA from AFD (ROC-AUC of 0.79 and 0.80, respectively). A linear discriminant analysis with stepwise variable selection using linear combinations of LV mass index, average e', LVGLS and basal strain correctly classified 79% of all cases. Conclusion: Simple echocardiographic parameters differentiate between different "hypertrophic" cardiac phenotypes. These have potential utility as a screening tool to guide further confirmatory testing.

A novel tool for case selection in endoscopic mucosal resection training.

BACKGROUND: As endoscopic mucosal resection (EMR) of large (≥ 20 mm) adenomatous nonpedunculated colonic polyps (LNPCPs) becomes widely practiced outside expert centers, appropriate training is necessary to avoid failed resection and inappropriate surgical referral. No EMR-specific tool guides case selection for endoscopists learning EMR. This study aimed to develop an EMR case selection score (EMR-CSS) to identify potentially challenging lesions for "EMR-naïve" endoscopists developing competency. METHODS: Consecutive EMRs were recruited from a single center over 130 months. Lesion characteristics, intraprocedural data, and adverse events were recorded. Challenging lesions with intraprocedural bleeding (IPB), intraprocedural perforation (IPP), or unsuccessful resection were identified and predictive variables identified. Significant variables were used to form a numerical score and receiver operating characteristic curves were used to generate cutoff values. RESULTS: Of 1993 LNPCPs, 286 (14.4 %) were in challenging locations (anorectal junction, ileocecal valve, or appendiceal orifice), 368 (18.5 %) procedures were complicated by IPB and 77 (3.9 %) by IPP; 110 (5.5 %) procedures were unsuccessful. The composite end point of IPB, IPP, or unsuccessful EMR was present in 526 cases (26.4 %). Lesion size, challenging location, and sessile morphology were predictive of the composite outcome. A six-point score was generated with a cutoff value of 2 demonstrating 81 % sensitivity across the training and validation cohorts. CONCLUSIONS: The EMR-CSS is a novel case selection tool for conventional EMR training, which identifies a subset of adenomatous LNPCPs that can be successfully and safely attempted in early EMR training.

Clostridioides difficile Infection: Clinical Practice and Health Outcomes in 6 Large Tertiary Hospitals in Eastern Australia.

Background: Clostridioides difficile infection (CDI) is associated with significant morbidity and mortality in both healthcare and community settings. We aimed to define the predisposing factors, risks for severe disease, and mortality determinants of CDI in eastern Australia over a 1-year period. Methods: This is an observational retrospective study of CDI in hospitalized patients aged ≥18 years in 6 tertiary institutions from 1 January 2016 to 31 December 2016. Patients were identified through laboratory databases and medical records of participating institutions. Clinical, imaging, and laboratory data were input into an electronic database hosted at a central site. Results: A total of 578 patients (578 CDI episodes) were included. Median age was 65 (range, 18-99) years and 48.2% were male. Hospital-onset CDI occurred in 64.0%. Recent antimicrobial use (41.9%) and proton pump inhibitor use (35.8%) were common. Significant risk factors for severe CDI were age <65 years (P < .001), malignancy within the last 5 years (P < .001), and surgery within the previous 30 days (P < .001). Significant risk factors for first recurrence included severe CDI (P = .03) and inflammatory bowel disease (P = .04). Metronidazole was the most common regimen for first episodes of CDI with 65.2% being concordant with Australian treatment guidelines overall. Determinants for death at 60 days included age ≥65 years (P = .01), severe CDI (P < .001), and antibiotic use within the prior 30 days (P = .02). Of those who received metronidazole as first-line therapy, 10.1% died in the 60-day follow-up period, compared to 9.8% of those who received vancomycin (P = .86). Conclusions: Patients who experience CDI are vulnerable and require early diagnosis, clinical surveillance, and effective therapy to prevent complications and improve outcomes.

Elevated Hepatic Steatosis Index is Associated with the Development of Adverse Maternal, but Not Adverse Neonatal, Outcomes: A Retrospective Cohort Study.

Objective: To determine whether an elevated hepatic steatosis index (HSI), a non-invasive test for possible metabolic dysfunction-associated fatty liver disease (MAFLD), is associated with the development of adverse pregnancy outcomes. Material and Methods: A retrospective cohort study was conducted on adult women with singleton pregnancies who delivered at two tertiary hospitals from August 2014 to December 2017. Aspartate aminotransaminase (AST) and alanine aminotransaminase (ALT) levels obtained 12 months pre-gravid, or during pregnancy but prior to screening for gestational diabetes mellitus (GDM), were extracted and linked with oral glucose tolerance test results. The HSI was calculated using the following equation: 8 × (ALT/AST ratio) + BMI (+2 if female; +2 if diabetes mellitus present) and considered elevated if >36. Multiple logistic regression analysis was used to quantify the association between elevated HSI and each composite adverse pregnancy outcome after adjusting for independent maternal risk factors. Results: Over 40-months, 11929 women were eligible and of these, 1885 had liver enzymes collected. Women with an elevated HSI (>36) were more likely multiparous and overweight/obese compared to those women with a non-elevated HSI (≤36). Elevated HSI was significantly associated with a composite of adverse maternal outcomes (adjusted odds ratio (aOR) 1.55 95% CI 1.11-2.17, p=0.01), although a non-significant increased risk of a composite of adverse neonatal outcomes occurred after multivariable adjustment (aOR 1.17, 95% CI 0.94-1.45, p=0.17). Conclusion: Over and above known maternal risk factors, women with elevated HSI were more likely to develop adverse maternal, but not adverse neonatal outcomes.

The Surface Morphology of Large Nonpedunculated Colonic Polyps Predicts Synchronous Large Lesions.

BACKGROUND & AIMS: Large (≥20 mm) nonpedunculated colorectal polyps (LNPCPs) may have synchronous LNPCPs in up to 18% of cases. The nature of this relationship has not been investigated. We aimed to examine the relationship between individual LNPCP characteristics and synchronous colonic LNPCPs. METHODS: Consecutive patients referred for resection of LNPCPs over 130 months until March 2022 were enrolled. Serrated lesions and mixed granularity LNPCPs were excluded from analysis. Patients with multiple LNPCPs resected were identified, and the largest was labelled as dominant. The primary outcome was the identification of individual lesion characteristics associated with the presence of synchronous LNPCPs. RESULTS: There were 3149 of 3381 patients (93.1%) who had a single LNPCP. In 232 (6.9%) a synchronous lesion was detected. Solitary lesions had a median size of 35 mm with a predominant Paris 0-IIa morphology (42.9%) and right colon location (59.5%). In patients with ≥2 LNPCPs, the dominant lesion had a median size of 40 mm, Paris 0-IIa (47.6%) morphology, and right colon location (65.9%). In this group, 35.8% of dominant LNPCPs were non-granular compared with 18.7% in the solitary LNPCP cohort. Non-granular (NG)-LNPCPs were more likely to demonstrate synchronous disease, with left colon NG-LNPCPs demonstrating greater risk (odds ratio, 4.78; 95% confidence interval, 2.95-7.73) than right colon NG-LNPCPs (odds ratio, 1.99; 95% confidence interval, 1.39-2.86). CONCLUSIONS: We found that 6.9% of LNPCPs have synchronous disease, with NG-LNPCPs demonstrating a greater than 4-fold increased risk. With post-colonoscopy interval cancers exceeding 5%, endoscopists must be cognizant of an individual's LNPCP phenotype when examining the colon at both index procedure and surveillance. CLINICALTRIALS: gov, NCT01368289; NCT02000141; NCT02198729.

Clinical and neurophysiological biomarkers of disease progression in amyotrophic lateral sclerosis.

INTRODUCTION/AIMS: Rate of disease progression (ΔFS), measured as change in the revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) and body mass index (BMI), are predictors of survival in amyotrophic lateral sclerosis (ALS). Our aim in this study was to assess the utility of these clinical biomarkers along with neurophysiological measures, such as the split hand index (SI), in monitoring disease progression. METHODS: Clinical trial data were collected from 107 patients recruited into the Tecfidera in ALS trial. The prognostic utility of clinical and neurophysiological measures, including ΔFS, BMI, SI, and neurophysiological index (NPI), were assessed cross-sectionally and longitudinally (40 weeks). The outcome measures of disease severity and progression included: (i) ALSFRS-R score; (ii) Medical Research Council (MRC) score; and (iii) forced vital capacity and sniff nasal inspiratory pressure. RESULTS: Fast-progressor ALS patients (ΔFS ≥1.1) exhibited significantly lower ALSFRS-R and total MRC scores at baseline. A baseline ΔFS score ≥1.1 was associated with a greater reduction in ALSFRS-R (P = .002) and MRC (P = .002) scores over 40 weeks. Baseline BMI <25 was also associated with faster reduction of ALSFRS-R and MRC scores. SI and NPI were associated with disease severity at baseline, but not with subsequent rate of disease progression. DISCUSSION: Implementation of the assessed clinical and neurophysiological biomarkers may assist in patient management and stratification into clinical trials.

The prevalence of metabolic dysfunction-associated fatty liver disease and its association on adverse pregnancy outcomes in women with gestational diabetes mellitus.

AIMS: To determine the prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) and its association on adverse pregnancy outcomes in women with gestational diabetes mellitus (GDM). METHODS: 380 women with GDM had a FibroScan® performed between 24 and 32 weeks. A Controlled Attenuation Parameter (CAP) ≥ 233.5 dB/m signified MAFLD. Gestational hypertension, pre-eclampsia and eclampsia contributed to a composite of adverse maternal outcomes. A composite of adverse neonatal outcomes included pre-term birth, hypoglycaemia, small/large-for-gestational age and admission to neonatal high dependency. Multiple logistic regression was used to determine independent associations with MAFLD. RESULTS: 147 (38.7 %) women had MAFLD. Higher pre-pregnancy BMI (median 28.4, IQR 24.7-33.0 kg/m2 vs median 24.0, IQR 21.7-26.5 kg/m2, p < 0.01) and rates of insulin therapy (62.2 % vs 40.7 %, p < 0.01) occurred in MAFLD over non-MAFLD women. MAFLD was independently associated with obesity (aOR 4.73 [95 % CI 2.53-8.86]) and insulin therapy (aOR 1.79 [95 % CI 1.12-2.85]). MAFLD and non-MAFLD women had comparable rates of adverse maternal (7.7 % vs 9.5 %, p = 0.56) and neonatal outcomes (75.4 % vs 68.8 %, p = 0.18). CONCLUSIONS: Within this GDM cohort, almost 40% had FibroScan®-detected MAFLD in mid-to-late gestation. MAFLD was not associated with worse pregnancy outcomes.

Asian Ethnicity and Femoral Geometry in Atypical Femur Fractures: Independent or Interdependent Risk Factors?

The earliest reports of atypical femur fractures (AFF) emerged from Asia. In the West, epidemiologic studies report a greater incidence of AFFs among subjects of Asian background. Asian ethnicity is an established risk factor for AFF, but clear mechanisms to explain this risk and implications for the general development of AFF are open questions. Ethno-specific differences in bisphosphonate action and femoral geometry have been proposed as hypotheses. In a retrospective cohort of 163 female patients presenting with AFFs or typical femur fractures (TFF), relative contributions of Asian ethnicity, proximal femoral geometry, and bisphosphonate use in AFF status were examined. There was a fourfold higher proportion of Asian subjects in the AFF compared with TFF groups (31.6%, 30/95 versus 7.4%, 5/68). Asian subjects had smaller femurs in femoral head, neck, and axial dimensions. A multiple logistic regression model for AFF status was fitted adding Asian ethnicity to three previously reported independent predictors of AFF including femoral geometry, which together comprise the Sydney AFF Score (age ≤80 years, femoral neck width <37 mm than non-Asian, lateral cortical width at lesser trochanter ≥5 mm). Asian ethnicity was a robust independent predictor of AFF, imparting sevenfold increase in the odds of AFF after adjusting for all three variables (95% confidence interval [CI] 2.2-23.2, p = 0.001) or for overall AFF score (95% CI 2.2-22.3 p = 0.001). Overall Asian subjects had higher rates of bisphosphonate use than non-Asian subjects (67.6% versus 47.2%, p = 0.034). Among AFF bisphosphonate users, Asian subjects had lower AFF scores than non-Asians (Sydney AFF Score ≤1, 45.5% Asian subjects versus 22.2% non-Asian subjects, p = 0.05). Asian ethnicity is a strong independent risk factor for AFF, unaccounted for by ethno-specific differences in proximal femoral geometry. Bisphosphonate use may be associated with a greater predisposition for AFF in Asian subjects compared with non-Asian subjects. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Comparison of the morphology and histopathology of large nonpedunculated colorectal polyps in the rectum and colon: implications for endoscopic treatment.

BACKGROUND AND AIMS: The risk of cancer in large nonpedunculated colorectal polyps ≥20 mm (LNPCPs) in the rectum relative to the remainder of the colon is unknown. We aimed to describe differences between rectal and colonic LNPCPs to better inform treatment decisions. METHODS: Patients with LNPCPs referred to tertiary centers for endoscopic resection within a prospective, multicenter, observational cohort were evaluated. Data recorded were participant demographics, LNPCP location, morphology, resection modality, and histopathologic data. Multiple logistic regression analysis was used to identify those variables independently associated with rectal versus nonrectal location in the colon. RESULTS: Patients with LNPCPs referred for endoscopic resection between July 2008 and July 2021 were included. Rectal LNPCPs (n = 618) were larger (median size, 40 mm vs 30 mm; P < .001) and more likely to be granular (79% vs 50%, P < .001) with a nodular component (53% vs 17%, P < .001) compared with nonrectal LNPCPs (n = 2787). Rectal LNPCPs were more likely to have tubulovillous histopathology (72% vs 47%, P < .001) and contain cancer (15% vs 6%, P < .001). After adjusting for the other features independently associated with location, cancer was more common in the rectum compared with the colon (odds ratio, 1.77; 95% confidence interval, 1.25-2.53). CONCLUSIONS: This study suggests that compared with LNPCPs in the rest of the colon, rectal LNPCPs are more likely to be larger and contain more advanced pathology. These findings have implications for curative endoscopic resection techniques particularly where early cancer is present. (Clinical trial registration numbers: NCT01368289 and NCT02000141.).

A retrospective cohort study of three wound catheter infusion analgesia regimes after midline laparotomy.

BACKGROUND: Local anesthetic wound infusion catheters are increasingly used postmidline laparotomy to reduce pain and opioid use, however there is little evidence to support any particular infusion regime. METHODS: A retrospective cohort study was undertaken of patients after midline laparotomy who had bilateral local anesthetic wound infusion catheters surgically placed. Patients were recruited into 3 cohorts: ropivacaine 0.2% 5-8 mL/hour continuous wound infusion, 10 mL programmed intermittent bolus 2 hourly, 20 mL programmed intermittent bolus 4 hourly. The primary outcome was the maximum daily Numerical Rating Pain Score with movement (dynamic pain score) recorded during first 96 hours postprocedure. Secondary outcomes included the maximum daily resting pain score and opioid utilization. RESULTS: In three cohorts of 70 patients (n=210), the maximum daily dynamic pain score in the intermittent bolus 2-hourly and 4-hourly cohorts was lower when compared with the continuous infusion group over the first 4 postoperative days. The mean difference in maximum daily pain score with respect to the continuous infusion regime was 0.8 (95% CI 0.2 to 1.4) for the intermittent bolus 2-hourly group and 0.6 (95% CI 0.0 to 1.2) for the 4-hourly group. Generalized estimating equation modeling indicates the reduction in dynamic pain score is greatest with the intermittent bolus 2-hourly regime over the first 72 hours postprocedure. The 2-hourly intermittent bolus regime was also associated with lower opioid utilization and local anesthetic exposure. CONCLUSIONS: Intermittent wound infusion catheter infusion regimes were associated with lower maximum daily dynamic pain scores, although the magnitude of this change may be of limited clinical significance.