Nevin Manimala

Braz J Cardiovasc Surg. 2025 Feb 12;40(1):e20240088. doi: 10.21470/1678-9741-2024-0088.

ABSTRACT

OBJECTIVER: The aim of this study was to determine the clinical outcomes of patients with acute type A aortic dissection comparing proximal aortic repair vs. total arch replacement.

METHODS: This was a retrospective cohort study. We included all acute type A aortic dissection procedures from January 2002 to November 2022. Groups were defined according to the extent of aortic replacement (hemiarch repair vs. total arch replacement). We collected data from pre, intra, and postoperative variables. Our main endpoints were stroke rate, spinal cord injury, and in-hospital mortality. We performed a statistical analysis for between-group comparisons according to the nature and distribution of variables. Bivariate analyses were done using the Mann-Whitney U test and for categorical variables, the Chi-square test or Fisher’s exact test. Significance was established at alpha level of 0.05.

RESULTS: We identified 107 acute type A aortic dissection procedures (69 hemiarch repairs vs. 38 total arch replacements). There were no differences in postoperative outcomes such as surgical site infection or acute kidney injury. Bleeding reoperation was more frequent in the hemiarch group (30% vs. 11 %). We did not find statistically significant differences in stroke rate, spinal cord injury, or in-hospital mortality.

CONCLUSION: Acute type A aortic dissection treatment is still a challenge. Total arch replacement does not increase the risk of major early postoperative complications in comparison to hemiarch repair. The extended repair seems to provide benefits such as a lower risk of reoperation. Total arch replacement should be performed in selected patients, as it may improve long-term outcomes.

PMID:39937874 | DOI:10.21470/1678-9741-2024-0088

PLoS One. 2025 Feb 12;20(2):e0317679. doi: 10.1371/journal.pone.0317679. eCollection 2025.

ABSTRACT

Inspiratory muscle weakness may affect exercise tolerance; however, the relationship between inspiratory muscle strength and the 6-minute walk distance (6MWD) in patients with acute heart failure (AHF) is unknown. This study aimed to quantitatively investigate the association between inspiratory muscle strength at the start of cardiac rehabilitation (CR) and 6MWD at discharge in patients with AHF. This single-center, retrospective, observational study enrolled 275 patients with AHF who underwent CR. Patients unable to walk before admission, with isometric knee extensor strength/weight (%IKES) < 0.3 kgf/kg at the start of CR, or unable to undergo examination were excluded. Maximum inspiratory mouth pressure (PI-max) was used as an indicator of inspiratory muscle strength and was measured at the start of CR. The measured PI-max was divided by the predicted value and used for analysis (%PI-max). The primary outcome was 6MWD, an indicator of exercise tolerance, and was measured at discharge. Statistical analysis was performed using multiple regression analysis, with 6MWD at discharge as the dependent variable and %PI-max at the start of CR as the independent variable. Covariates were age, New York Heart Association class, physical frailty, and %IKES at the start of CR. The final analysis included 94 patients (median age 83.0 years, 57.5% male). Multiple regression analysis showed that %PI-max at the start of CR was significantly associated with 6MWD at discharge even after adjustment for covariates (β = 0.223, 95% confidence interval: 0.063-0.382, p = 0.007). PI-max was a factor associated with 6MWD at discharge in patients with AHF. In conclusion, increased inspiratory muscle strength may contribute to improved 6MWD in patients with AHF.

PMID:39937872 | DOI:10.1371/journal.pone.0317679

Mutagenesis. 2025 Feb 12:geae029. doi: 10.1093/mutage/geae029. Online ahead of print.

ABSTRACT

DNA damage is a common event in cells, resulting from both internal and external factors. The maintenance of genomic integrity is vital for cellular function and physiological processes. The inadequate repair of DNA damage results in the genomic instability, which has been associated with the development and progression of various human diseases. Accumulation of DNA damage can lead to multiple diseases, such as neurodegenerative disorders, cancers, immune deficiencies, infertility and aging. This comprehensive review delves the impact of alterations in DNA damage response genes (DDR) and tries to elucidate how and to what extent the same traits modulate diverse major human diseases, such as cancer, neurodegenerative diseases, and immunological disorders. DDR is apparently the trait connecting important complex disorders in humans. However, the pathogenesis of the above disorders and diseases are different and leading to the divergent consequences. It is important to discover the switch(es) that direct further the pathogenic process either to proliferative, or degenerative diseases. Our understanding the influence of DNA damage on diverse human disorders may enable a development of the strategies to prevent, diagnose, and treat these diseases. In our article, we analysed publicly available GWAS summary statistics from the NHGRI-EBI GWAS Catalog and identified 12,009 single nucleotide polymorphisms (SNPs) associated with cancer. Among these, 119 SNPs were found in DDR pathways, exhibiting significant p-values. Additionally, we identified 44 SNPs linked to various cancer types and neurodegenerative diseases (NDDs), including four located in DDR-related genes: ATM, CUX2, and WNT3. Furthermore, 402 SNPs were associated with both cancer and immunological disorders, with two found in DDR gene RAD51B. This highlights the versatility of the DDR pathway in multifactorial diseases. However, the specific mechanisms that regulate DDR to initiate distinct pathogenic processes remain to be elucidated.

PMID:39937585 | DOI:10.1093/mutage/geae029

Cancer. 2025 Feb 15;131(4):e35725. doi: 10.1002/cncr.35725.

ABSTRACT

BACKGROUND: Previous estimates of the number of cancers attributable to physical inactivity in the United States have typically focused on only three malignancies (colon, endometrial, and postmenopausal breast cancer). Contemporary epidemiologic evidence suggests that physical inactivity could contribute to up to 15 types of cancer, and a dose-response effect has been demonstrated for 13 of these. This study estimated the number of cancers diagnosed in the United States in 2015 due to physical inactivity for these 13 sites.

METHODS: Data from the 2005 National Health Interview Survey were used to estimate physical activity prevalence and, with the assumption of a 10-year latency period, 2015 cancer incidence data from the National Program of Cancer Registries and Surveillance, Epidemiology, and End Results Incidence US Cancer Statistics Public Use Database.

RESULTS: The potential impact fraction was estimated to be 4.1%, which meant that 30,951 of 761,625 incident cancers at the 13 sites could have been prevented in the United States in 2015 if adults had increased physical activity by one category in 2005 (approximately 7.5 additional metabolic equivalent task hours per week [MET-h/week]). Theoretically, 85,415 of 761,625 incident cancers at the 13 sites (population attributable fraction, 11.2%) could have been prevented if all adults had achieved the highest level of physical activity (>30 MET-h/week).

CONCLUSIONS: When estimates are based on updated epidemiologic evidence regarding physical inactivity and cancer risk, substantially more cancers are attributable to physical inactivity than previously reported. A greater focus on physical activity promotion is warranted for cancer control in the United States.

PMID:39937584 | DOI:10.1002/cncr.35725

Lymphat Res Biol. 2025 Feb 12. doi: 10.1089/lrb.2024.0006. Online ahead of print.

ABSTRACT

Background: Female genital lymphedema (FGL) is a challenging disease, and appropriate preoperative evaluation is crucial before surgical treatments. Computed tomography (CT) is expected useful for FGL evaluation, but little is known. This study aimed to clarify characteristic CT findings of FGL with a case report of CT findings-guided lymphaticovenous anastomosis (LVA). Methods: Medical charts of secondary lower extremity lymphedema patients who underwent CT and indocyanine green (ICG) lymphography were reviewed. Genital regions with dermal backflow patterns on ICG lymphography were diagnosed as FGL. Prevalence of characteristic CT findings of lymphedema was compared between genitalia regions with and without FGL. A case of genital lymphedema treated with LVA under the guidance of CT findings was presented. Results: A total of 51 patients (32 with FGL, and 19 without FGL) were included in this study. Genital ICG included stages 0/I/II/III/IV/V in 19 (37.3%)/5 (9.8%)/11 (21.6%)/9 (17.6%)/7 (13.7%)/0 (0%) cases, respectively. Characteristic CT findings included thick skin in 14 (27.5%), thick fascia in 17 (33.3%), high density of the superficial fat in 11 (21.6%), high density of the deep fat in 13 (25.5%), fluid collection in 8 (15.7%), detectable inguinal lymph node in 42 (82.4%), and honeycomb appearance in 7 regions (13.7%). Between genital regions with and without FGL, there were statistically significant differences in all the characteristic CT findings (p < 0.05). Conclusions: Characteristic CT findings of secondary FGL were identified. Preoperative CT evaluation may be useful for selecting appropriate LVA sites for optimal results.

PMID:39937577 | DOI:10.1089/lrb.2024.0006

J Surg Res. 2025 Jan;305:237-245. doi: 10.1016/j.jss.2024.11.031. Epub 2024 Dec 27.

ABSTRACT

INTRODUCTION: This study aimed to compare the outcomes of three-dimensional (3D) image-guided video-assisted thoracic surgery (VATS) segmentectomy performed with and without preoperative localization for the resection of small pulmonary nodules.

METHOD: Between July 2015 and December 2022, 439 patients who underwent 3D image-guided VATS segmentectomy for early-stage lung cancer were enrolled. Based on whether preoperative localization was performed, the patients were divided into two groups as follows: the localization (n = 96) and nonlocalization groups (n = 343). The primary endpoints were the resection success rate and surgical margins.

RESULTS: Resection was successfully performed in 95 (99.0%) and 340 (99.1%) patients in the localization and nonlocalization groups, respectively (P = 1.000). One and three patients in the localization and nonlocalization groups, respectively, required conversion to extended segmentectomy due to inadequate surgical margins. The median surgical margins were 20 (range, 14-30) mm and 22 (range, 14-30) mm in the localization and nonlocalization groups, respectively (P = 0.410). However, overall complications were significantly more frequent in the localization group (9.4%) than in the nonlocalization group (4.1%; P = 0.040). This result was further supported by findings from multivariate logistic regression analysis. A subgroup analysis of high-risk small pulmonary nodules indicated no statistically significant differences between the groups concerning the primary endpoints.

CONCLUSIONS: 3D image-guided VATS segmentectomy performed with and without preoperative localization had comparable resection success rates and surgical margins. However, the procedure without preoperative localization was associated with fewer postoperative complications.

PMID:39937556 | DOI:10.1016/j.jss.2024.11.031

J Surg Res. 2025 Jan;305:231-236. doi: 10.1016/j.jss.2024.11.040. Epub 2024 Dec 27.

ABSTRACT

INTRODUCTION: Operative selection in metabolic surgery is a complex, collaborative process between patient and surgeon, considering factors such as risk, cost, desired weight loss, and resolution of associated comorbidities. This study aimed to explore the association of patient demographics and body mass index on operative selection.

MATERIALS AND METHODS: Retrospective review of 388 patient surveys prior to initial surgical visit (2020-2023) was conducted at a single institution. Patient demographics as well as operation preference prior to the initial visit and procedure ultimately performed were evaluated. Categorical variables were summarized as frequency and percentage and compared using chi-square tests. Continuous measures were summarized as means and standard deviations and compared using analysis of variance. Proceeding with the originally preferred procedure was modeled using multivariable logistic regression.

RESULTS: Prior to the initial visit, 62.1% of patients indicated preference toward sleeve gastrectomy, while 14.9% indicated preference toward Roux-en-Y gastric bypass. Notably, initial patient preferences aligned with the actual procedure, with 69.3% of sleeve gastrectomy-desiring patients and 62.1% of Roux-en-Y gastric bypass-desiring patients receiving their preferred operation. Factors associated with actual procedure performed included male sex (OR 3.27 [1.04, 10.26]) and presence of preoperative sleep apnea (OR 0.41 [0.20,0.81]) and hypertension (OR 0.46 [0.22,0.96]). Other factors that showed an association with preference, but were not statistically significant, included body mass index.

CONCLUSIONS: Patients’ comorbidities and sex are associated with the likelihood of undergoing the preferred operation procedure. However, most patients underwent their preferred procedure, highlighting the importance of patients’ selection.

PMID:39937555 | DOI:10.1016/j.jss.2024.11.040

JAMA Dermatol. 2025 Feb 12. doi: 10.1001/jamadermatol.2024.6434. Online ahead of print.

ABSTRACT

IMPORTANCE: Frontal fibrosing alopecia (FFA) is an inflammatory and scarring form of hair loss of increasing prevalence that most commonly affects women. An improved understanding of the genetic basis of FFA will support the identification of pathogenic mechanisms and therapeutic targets.

OBJECTIVE: To identify novel genomic loci at which common genetic variation affects FFA susceptibility and assess nonadditive effects on genetic risk between susceptibility loci.

DESIGN, SETTING, AND PARTICIPANTS: Four genome-wide association studies were combined using an SE-weighted meta-analysis. Within the major histocompatibility complex (MHC) locus, stepwise conditional analysis was undertaken to determine independently associated classical MHC class I alleles. Statistical tests for epistatic interaction were performed between risk alleles at the MHC and endoplasmic reticulum aminopeptidase 1 (ERAP1) loci.

MAIN OUTCOMES AND MEASURES: Genome-wide significant locus associated with FFA and nonadditive effects on genetic risk between susceptibility loci.

RESULTS: Of 6668 included patients, there were 1585 European female individuals with FFA and 5083 controls. Genome-wide significant associations were identified at 4 genomic loci, including a novel susceptibility locus at 5q15, and the association signal could be fine-mapped to a single nucleotide substitution (rs10045403) in the 5′ untranslated region of ERAP1 (rs10045403; odds ratio, 1.30; 95% CI, 1.19-1.43; P = 3.6 × 10-8). Within the MHC, FFA risk was statistically independently associated with HLA-A*11:01, HLA-A*33:01, HLA-B*07:02, and HLA-B*35:01. FFA risk was affected by genetic variation at the ERAP1 locus only in individuals who carried at least 1 of the MHC class I risk alleles.

CONCLUSIONS AND RELEVANCE: In this genome-wide meta-analysis, a supra-additive effect of genetic variation was found that affected peptide trimming and antigen presentation on FFA susceptibility. Patients with FFA may benefit from emerging therapeutic approaches that modulate ERAP-mediated processes.

PMID:39937552 | DOI:10.1001/jamadermatol.2024.6434

JAMA Psychiatry. 2025 Feb 12. doi: 10.1001/jamapsychiatry.2024.4534. Online ahead of print.

ABSTRACT

IMPORTANCE: Identifying anatomy causally involved in psychosis could inform therapeutic neuromodulation targets for schizophrenia.

OBJECTIVE: To assess whether lesions that cause secondary psychosis have functional connections to a common brain circuit.

DESIGN, SETTING, AND PARTICIPANTS: This case-control study mapped functional connections of published cases of lesions causing secondary psychosis compared with control lesions unassociated with psychosis. Published cases of lesion-induced psychosis were analyzed in a computational laboratory. Participants had documented brain lesions associated with new-onset psychotic symptoms without a history of psychosis. Control cases included 1156 patients with lesions not associated with psychosis. Generalizability across lesional datasets was assessed using an independent cohort of 181 patients with brain lesions who subsequently underwent neurobehavioral testing. Data were analyzed from June 2022 to April 2024.

EXPOSURES: Lesions causing secondary psychosis.

MAIN OUTCOMES AND MEASURES: Psychosis or no psychosis.

RESULTS: A total of 153 lesions from published cases were determined to be causal of psychosis, 42 of which were described as schizophrenia or schizophrenia-like (71 [46%] patients were male, 82 [54%] female; mean [SD] age, 50.0 [20.8] years). Lesions that caused secondary psychosis mapped to a common brain circuit defined by functional connectivity to the posterior subiculum of the hippocampus (84% functional overlap, family-wise error [FWE] rate corrected P < 5 × 10-5). At a lower statistical threshold (>75% overlap, FWE-corrected P < 5 × 10-4), this circuit included the ventral tegmental area, retrosplenial cortex, lobule IX and dentate nucleus of the cerebellum, and the mediodorsal and midline nuclei of the thalamus. This circuit was consistent when derived from schizophrenia-like cases (spatial r = 0.98). We repeated these analyses after excluding lesions intersecting the hippocampus (n = 47) and found a consistent functional connectivity profile (spatial r = 0.98) with the posterior subiculum remaining the center of connectivity (>75% overlap, FWE-corrected P < 5 × 10-5), demonstrating a circuit-level effect. In an independent observational cohort of patients with penetrating head trauma (n = 181), lesions associated with symptoms of psychosis exhibited significantly similar connectivity profiles to the lesion-derived psychosis circuit (suspiciousness, P = .03; unusual thought content, P = .046). Voxels in the rostromedial prefrontal cortex are highly correlated with this psychosis circuit (spatial r = 0.82), suggesting the rostromedial prefrontal cortex as a promising transcranial magnetic stimulation target for psychosis.

CONCLUSIONS AND RELEVANCE: Lesions that cause secondary psychosis affect a common brain circuit in the hippocampus. These results can help inform therapeutic neuromodulation targeting.

PMID:39937525 | DOI:10.1001/jamapsychiatry.2024.4534

JAMA Netw Open. 2025 Feb 3;8(2):e2457666. doi: 10.1001/jamanetworkopen.2024.57666.

ABSTRACT

IMPORTANCE: Dust storms are projected to increase with climate change. The short-term health outcomes associated with dust storms in the US are not well characterized, especially for morbidity outcomes.

OBJECTIVE: To estimate associations between dust storms and diagnosis-specific emergency department (ED) visits during 2005 to 2018.

DESIGN, SETTING, AND PARTICIPANTS: In this cross-sectional study using a time-stratified case-crossover design, short-term associations between dust storms and ED visits were estimated at the zip code level using conditional Poisson analysis with adjustment for meteorology and within-month trends. Same-day dust storm events and storm events within a lag period of up to 7 days were considered. State-wide patient-level ED visit records acquired from 3 state health departments (Arizona, California, and Utah) were analyzed. Data were analyzed between April 21 and November 12, 2024.

EXPOSURES: Dust storm events were reported by the US National Weather Service and assigned to each patient zip code that had at least a 5% areal overlap with the National Weather Service forecast zone.

MAIN OUTCOMES AND MEASURES: Patient-level ED visits for asthma, chronic obstructive pulmonary disease, culture-negative pneumonia, congestive heart failure (CHF), cerebrovascular disease, ischemic heart disease, and visits due to motor vehicle accidents.

RESULTS: The analysis included 33 500 ED visits among the outcomes of interest (5717 children aged 0-17 years [17.1%] and 11 150 adults aged >65 years [33.3%]; 17 394 male [51.9%] and 16 104 female [48.1%]; 2829 Black [8.4%] and 22 537 White [67.2%]; 9256 Hispanic [27.6%]) and 206 dust-impacted zip codes. The strongest associations between dust storms and ED visits were found for asthma (lag 0-2 relative risk [RR], 1.06; 95% CI, 1.01-1.11; P = .03), culture-negative pneumonia (lag 0-7 RR, 1.06; 95% CI, 1.02-1.10; P = .002), CHF (lag 0-7 RR, 1.06; 95% CI, 1.01-1.10; P = .01), and motor vehicle accidents (lag 0 RR, 1.13; 95% CI, 1.04-1.23; P = .003). Associations of dust storm exposure with ischemic heart disease were mostly protective (eg, lag 0-2 RR, 0.89; 95% CI, 0.84-0.95; P < .001). Associations of dust storm exposure with risk of ED visits for CHF and motor vehicle accidents were robust against adjustment for ambient ozone (eg, CHF: RR, 1.08; 95% CI, 1.03-1.13; P = .003) and nitrogen dioxide (eg, CHF: RR, 1.08; 95% CI, 1.03-1.13; P = .003) air pollution.

CONCLUSIONS AND RELEVANCE: In this study, dust storms were positively associated with ED visits for asthma, pneumonia, heart failure, and motor vehicle accidents. These findings contribute to our understanding of the association of dust storms with morbidity in the US and potential outcomes under a changing climate.

PMID:39937479 | DOI:10.1001/jamanetworkopen.2024.57666