Nevin Manimala

Anatol J Cardiol. 2023 Nov 14. doi: 10.14744/AnatolJCardiol.2023.3373. Online ahead of print.

ABSTRACT

BACKGROUND: A novel risk prediction model appears to be urgently required to improve the assessment of thrombotic risk in overweight patients with nonvalvular atrial fibrillation (NVAF). We developed a novel body mass index (BMI)-based thromboembolic risk score (namely AB2S score) for these patients.

METHODS: A total of 952 overweight patients with NVAF were retrospectively enrolled in this study with a 12-month follow-up. The primary endpoint was 1-year systemic thromboembolism and the time to thrombosis (TTT). The candidate risk variables identified by logistic regression analysis were included in the final nomogram model to construct AB2S score. The measures of model fit were evaluated using area under the curve (AUC), C-statistic, and calibration curve. The performance comparison of the AB2S score to the CHADS2 and CHA2DS2-VASc score was performed in terms of the AUC and decision analysis curve (DAC).

RESULTS: The AB2S score was constructed using 7 candidate risk variables, including a 3-category BMI (25 to 30, 30 to 34, or ≥35 kg/m2). It yielded a c-index of 0.885 (95% CI, 0.814-0.954) and an AUC of 0.885 (95% CI, 0.815-0.955) for predicting 1-year systemic thromboembolism in patients with NVAF. Compared to the CHADS2 score and CHA2DS2-VASc score, the AB2S score had greater AUC and DAC values in predicting the thromboembolic risk and better risk stratification in TTT (P <.0001, P =.082, respectively).

CONCLUSION: Our results highlighted the importance of a BMI-based AB2S score in determining systemic thromboembolism risk in overweight patients with NVAF, which may aid in decision-making for these patients to balance the effectiveness of anticoagulation from the underlying thrombotic risk.

PMID:37961898 | DOI:10.14744/AnatolJCardiol.2023.3373

J R Soc Med. 2023 Oct;116(10):343-350. doi: 10.1177/01410768231203922.

NO ABSTRACT

PMID:37961883 | DOI:10.1177/01410768231203922

Curr Med Res Opin. 2023 Nov 14:1-20. doi: 10.1080/03007995.2023.2283204. Online ahead of print.

ABSTRACT

OBJECTIVES: Ureteral injuries (UIs) during surgical procedures can have serious consequences for patients. Although UIs can result in substantial clinical burden, few studies report the impact of these injuries on payer reimbursement and patient cost-sharing. This retrospective study evaluated 30-day, 90-day, and 1-year healthcare resource utilization for patients with UIs and estimated patient and payer costs.

METHODS: Patients aged ≥ 12 years who underwent abdominopelvic surgery from January 2016 to December 2018 were identified in a United States claims database. Patients were followed for 1 year to estimate all-cause healthcare visits and costs for patients and payers. Surgeries resulting in UIs within 30 days from the surgery date were matched to surgeries without UIs to estimate UI-attributable visits and costs.

RESULTS: Five hundred twenty-two patients with UIs were included. Almost a third (29.9%) of patients with UIs had outpatient surgery. Patients with UIs had slightly more healthcare visits, and a 15.3% higher 30-day hospital readmission rate than patients without UIs. Patient costs due to UIs were not statistically significant, but annual payer costs attributable to UIs were $38,859 [95% CI: 28,142-49,576], largely driven by inpatient costs.

CONCLUSIONS: UIs add substantial cost for payers and result in more healthcare visits for patients. These findings highlight the importance of including inpatient and outpatient settings for UI prevention. Although UIs are rare, the associated patient and payer burdens are high; thus, protocols or techniques are needed to recognize and avert UIs, as current guideline recommendations are lacking.

PMID:37961772 | DOI:10.1080/03007995.2023.2283204

Acta Cardiol. 2023 Nov 14:1-11. doi: 10.1080/00015385.2023.2277624. Online ahead of print.

ABSTRACT

BACKGROUND: Cardiac resynchronisation therapy (CRT) can be necessary in patients with chronic heart failure, who have already been provided with transvenous cardiac implantable electrical devices. Upgrade procedures revealed controversial results, while long-term outcomes regarding underlying Ischaemic- (ICM) or Non-Ischaemic heart disease (NICM) have yet to be described.

METHODS: The Mannheim Cardiac Resynchronisation Therapy Registry (MARACANA) was designed as a retrospective observational single-centre registry, including all CRT implantations from 2013-2021 (n = 459). CRT upgrades (n = 136) were retrospectively grouped to either ICM (n = 84) or NICM (n = 52) and compared for New York Heart Association classification (NYHA), paced QRS-width, left ventricular ejection fraction (LVEF), tricuspid annular plane systolic excursion (TAPSE) and other heart failure modification aspects in the long-term (59.3 ± 5 months).

RESULTS: Baseline-characteristics including paced QRS-width, upgrade indications or NYHA-classification were comparable for both groups (group comparison p>.05). The CRT upgrade improved NYHA (ICM: 2.98 ± 0.4 to 2.29 ± 0.7, NICM: 2.94 ± 0.5 to 2.08 ± 0.5) and the LVEF (ICM: 27.2 ± 6.6 to 38.25 ± 8.8, NICM: 30.2 ± 9.4 to 38.7 ± 13.8%) after five years, irrespective of underlying heart disease (each group p < .05, group comparison p>.05). Only ICM revealed significant improvements in TAPSE (15.9 ± 4.1 to 18.9 ± 4.1 mm) and narrowing of the paced QRS-width (185.4 ± 29 to 147.2 ± 16.3 ms) after five years (each p < .05).

CONCLUSIONS: Upgrade to CRT might improve heart failure symptoms and left-ventricular systolic function in the long-term, irrespective of underlying ischaemic or non-ischaemic heart disease.

PMID:37961770 | DOI:10.1080/00015385.2023.2277624

ArXiv. 2023 Nov 2:arXiv:2311.01625v1. Preprint.

ABSTRACT

Persistent homology (PH) characterizes the shape of brain networks through the persistence features. Group comparison of persistence features from brain networks can be challenging as they are inherently heterogeneous. A recent scale-space representation of persistence diagram (PD) through heat diffusion reparameterizes using the finite number of Fourier coefficients with respect to the Laplace-Beltrami (LB) eigenfunction expansion of the domain, which provides a powerful vectorized algebraic representation for group comparisons of PDs. In this study, we advance a transposition-based permutation test for comparing multiple groups of PDs through the heat-diffusion estimates of the PDs. We evaluate the empirical performance of the spectral transposition test in capturing within- and between-group similarity and dissimilarity with respect to statistical variation of topological noise and hole location. We also illustrate how the method extends naturally into a clustering scheme by subtyping individuals with post-stroke aphasia through the PDs of their resting-state functional brain networks.

PMID:37961747 | PMC:PMC10635302

ArXiv. 2023 Oct 31:arXiv:2311.00085v1. Preprint.

ABSTRACT

Cells that collide with each other repolarize away from contact, in a process called contact inhibition of locomotion (CIL), which is necessary for correct development of the embryo. CIL can occur even when cells make a micron-scale contact with a neighbor – much smaller than their size. How precisely can a cell sense cell-cell contact and repolarize in the correct direction? What factors control whether a cell recognizes it has contacted a neighbor? We propose a theoretical model for the limits of CIL where cells recognize the presence of another cell by binding the protein ephrin with the Eph receptor. This recognition is made difficult by the presence of interfering ligands that bind nonspecifically. Both theoretical predictions and simulation results show that it becomes more difficult to sense cell-cell contact when it is difficult to distinguish ephrin from the interfering ligands, or when there are more interfering ligands, or when the contact width decreases. However, the error of estimating contact position remains almost constant when the contact width changes. This happens because the cell gains spatial information largely from the boundaries of cell-cell contact. We study using statistical decision theory the likelihood of a false positive CIL event in the absence of cell-cell contact, and the likelihood of a false negative where CIL does not occur when another cell is present. Our results suggest that the cell is more likely to make incorrect decisions when the contact width is very small or so large that it nears the cell’s perimeter. However, in general, we find that cells have the ability to make reasonably reliable CIL decisions even for very narrow (micron-scale) contacts, even if the concentration of interfering ligands is ten times that of the correct ligands.

PMID:37961746 | PMC:PMC10635320

ArXiv. 2023 Oct 31:arXiv:2310.20527v1. Preprint.

ABSTRACT

PURPOSE: To study the effect of proton linear energy transfer (LET) on rib fracture in breast cancer patients treated with pencil-beam scanning proton therapy (PBS) using a novel tool of dose-LET volume histogram (DLVH).

METHODS: From a prospective registry of patients treated with post-mastectomy proton therapy to the chest wall and regional lymph nodes for breast cancer between 2015 and 2020, we retrospectively identified rib fracture cases detected after completing treatment. Contemporaneously treated control patients that did not develop rib fracture were matched to patients 2:1 considering prescription dose, boost location, reconstruction status, laterality, chest wall thickness, and treatment year. The DLVH index, V(d, l), defined as volume(V) of the structure with at least dose(d) and LET(l), was calculated. DLVH plots between the fracture and control group were compared. Conditional logistic regression (CLR) model was used to establish the relation of V(d, l) and the observed fracture at each combination of d and l. The p-value derived from CLR model shows the statistical difference between fracture patients and the matched control group. Using the 2D p-value map, the DLVH features associated with the patient outcomes were extracted.

RESULTS: Seven rib fracture patients were identified, and fourteen matched patients were selected for the control group. The median time from the completion of proton therapy to rib fracture diagnosis was 12 months (range 5 to 14 months). Two patients had grade 2 symptomatic rib fracture while the remaining 5 were grade 1 incidentally detected on imaging. The derived p-value map demonstrated larger V(0-36 Gy[RBE], 4.0-5.0 keV/um) in patients experiencing fracture (p<0.1).

CONCLUSIONS: In breast cancer patients receiving PBS, a larger volume of chest wall receiving moderate dose and high LET may result in increased risk of rib fracture.

PMID:37961731 | PMC:PMC10635309

bioRxiv. 2023 Oct 27:2023.10.27.564319. doi: 10.1101/2023.10.27.564319. Preprint.

ABSTRACT

Since the first Genome-Wide Association Studies (GWAS), thousands of variant-trait associations have been discovered. However, the sample size required to detect additional variants using standard univariate association screening is increasingly prohibitive. Multi-trait GWAS offers a relevant alternative: it can improve statistical power and lead to new insights about gene function and the joint genetic architecture of human phenotypes. Although many methodological hurdles of multi-trait testing have been discussed, the strategy to select trait, among overwhelming possibilities, has been overlooked. In this study, we conducted extensive multi-trait tests using JASS (Joint Analysis of Summary Statistics) and assessed which genetic features of the analysed sets were associated with anincreased detection of variants as compared to univariate screening. Our analyses identified multiple factors associated with the gain in the association detection in multi-trait tests. Together, these factors of the analysed sets are predictive of the gain of the multi-trait test (Pearson’s ρ equal to 0.43 between the observed and predicted gain, P < 1.6 × 10 ^-60 ). Applying an alternative multi-trait approach (MTAG, multi-trait analysis of GWAS), we found that in most scenarios but particularly those with larger numbers of traits, JASS outperformed MTAG. Finally, we benchmark several strategies to select set of traits including the prevalent strategy of selecting clinically similar traits, which systematically underperformed selecting clinically heterogenous traits or selecting sets that issued from our data-driven models. This work provides a unique picture of the determinant of multi-trait GWAS statistical power and outline practical strategies for multi-trait testing.

PMID:37961722 | PMC:PMC10634875 | DOI:10.1101/2023.10.27.564319

Res Sq. 2023 Nov 1:rs.3.rs-3496738. doi: 10.21203/rs.3.rs-3496738/v1. Preprint.

ABSTRACT

Background: Recent decades have seen an exponential rise in global obesity prevalence, with rates nearly doubling in a span of forty years. A comprehensive knowledge base regarding the systemic effects of obesity is required to create new preventative and therapeutic agents effective at combating the current obesity epidemic. Previous studies of diet-induced obesity utilizing mouse models have demonstrated a difference in bodyweight gain by sex. In such studies, female mice gained significantly less weight than male mice when given the same high fat (HF) diet, indicating a resistance to diet-induced obesity. Research has also shown sex differences in gut microbiome composition between males and females, indicated to be in part a result of sex hormones. Understanding metabolic differences between sexes could assist in the development of new measures for obesity prevention and treatment. This study aimed to characterize sex differences in weight gain, plasma lipid profiles, fecal microbiota composition, and fecal short chain fatty acid levels. We hypothesized a role for the gut microbiome in these sex differences that would be normalized following microbiome depletion. Methods: A mouse model was used to study these effects. Mice were divided into treatment groups by sex, diet, and presence/absence of an antibiotic cocktail to deplete genera in the gut microbiome. We hypothesized that sex differences would be present both in bodyweight gain and systemic measures of obesity, including hormone and circulating free fatty acid levels. Results: We determined statistically significant differences for sex and/or treatment for the outcome measures. We confirm previous findings in which male mice gained significantly more weight than female mice fed the same high fat diet. However, sex differences persisted following antibiotic administration for microbiome depletion. Conclusions: We conclude that sex differences in the gut microbiome may contribute to sex differences in obesity, but they do not explain all of the differences.

PMID:37961721 | PMC:PMC10635401 | DOI:10.21203/rs.3.rs-3496738/v1

medRxiv. 2023 Oct 23:2023.10.23.23297392. doi: 10.1101/2023.10.23.23297392. Preprint.

ABSTRACT

BACKGROUND: Postpartum Depression (PPD) is a major health challenge with potentially devastating maternal and physical health outcomes. Development of diabetes mellitus has been hypothesized as one the potential adverse effects of PPD among mothers in the postpartum period but this association has not been adequately studied. This study aimed at determining prevalence of postpartum depression and its association with diabetes mellitus among mothers in Mbarara District, southwestern Uganda.

METHODS: This was a facility based cross sectional study of 309 mothers between 6 ^th week to 6 ^th month after childbirth. Using proportionate stratified consecutive sampling, mothers were enrolled from postnatal clinics of two health facilities, Mbarara Regional Referral Hospital and Bwizibwera Health center IV. PPD was diagnosed using the Mini-International Neuropsychiatric Interview (MINI 7.0.2) for the Diagnostic and Statistical Manual of Mental Disorders, 5 ^th Edition (DSM-5). Diabetes mellitus was diagnosed by measuring Hemoglobin A1c (HbA1c). Logistic regression was used to determine the association of PPD and diabetes mellitus among mothers.

RESULTS: The study established that PPD prevalence among mothers of 6 ^th weeks to 6 ^th months postpartum period in Mbarara was 40.5% (95% CI: 35.1-45.1%). A statistically significant association between postpartum depression and diabetes mellitus in mothers between 6 weeks and 6 months postpartum was established. The prevalence of diabetes mellitus among mothers with PPD was 28% compared to 13.6% among mothers without PPD Mothers with PPD had 3 times higher odds of being newly diagnosed with diabetes between 6 weeks and 6 months postpartum as compared to those without PPD during the same period (aOR=3.0, 95% CI: 1.62-5.74, p=0.001).

CONCLUSION AND RECOMMENDATIONS: Postpartum women within 6 ^th weeks to 6 ^th months have higher risks of developing diabetes mellitus. Research is needed to determine if targeted diabetes mellitus screening, prevention interventions and management will help reduce the burden.

PMID:37961709 | PMC:PMC10635159 | DOI:10.1101/2023.10.23.23297392