Intermediate Risk Research Articles

Rationale of restaging transurethral resection of bladder tumor in patients with nonmuscle invasive bladder cancer in the current era

Background: We present retrospective data of patients with nonmuscle invasive bladder cancer (NMIBC) who underwent restaging transurethral resection of bladder tumor (Re-TURBT) at a tertiary care center. Materials and Methods: Records of all NMIBC patients undergoing Re-TURBT between March 2021 and September 2023 were retrospectively analyzed. Patients were risk stratified based on TURBT pathology. Re-TURBT was performed between 4 and 6 weeks. Adverse features such as number, size, and appearance were noted. Patients with persistent disease at Re-TURBT were counseled for early cystectomy with urinary diversion or intravesical Bacillus Calmette–Guerin (BCG). In case of disease upstaging, patients were counseled for radical cystectomy. Results: Thirty-eight NMIBC patients (30 males and 8 females) underwent Re-TURBT. Six patients had residual/persistent disease at 6 weeks, all high risk and high grade (HG, P value not significant, P = 0.31). There was no association with number and appearance of tumors with residual/persistence at 6 weeks. The mean lesion size on imaging in cases with and without residual disease was 3.32 ± 0.86 versus 3.39 ± 0.92 cm, respectively, P value not significant (0.868). There was no residual disease in the low-grade (LG) pT1 group, but HG pTa and pT1 (n = 3) had residual disease. Four HG pT1 patients opted for early cystectomy. Two patients each had pT0 and two pT2. At 3 months of follow-up, urethral strictures were seen both in high risk and intermediate risk. Among four patients who had stricture, meatal stenosis was common (50%, n = 2). Two patients had long-segment stricture requiring perineal urethrostomy with stage I Johannsen repair. All HG pT1 lesion patients eventually underwent cystectomy (3 were under staged and two treated completely with TURBT, one with TURBT + BCG and one patient progressed to metastasis). Conclusion: Re-TURBT is essential for the management of HG pTa and HG pT1 lesions for accurate staging and treatment of residual disease. However, LG pT1 patients can safely be excluded from Re-TURBT.

Prospective Evaluation of Supplemental External Beam Radiation Therapy With Palladium-103 Prostate Brachytherapy: Long-Term Results of the 44/20/0 Trials

PurposeThe 44/20 and 20/0 randomized trials evaluated whether different external beam radiation therapy (EBRT) dosing regimens prior to brachytherapy impacted biochemical failure (BF). We report long-term outcomes of both trials, and evaluate whether biological equivalent dose (BED) was associated with reduced BF in the combined trial cohort. Materials/methodsBoth trials enrolled patients with clinical T1c-T2b, Gleason score 7-9 and/or a pre-treatment prostate-specific antigen (PSA) 10-20 ng/ml disease. The 44/20 trial randomized patients to 44Gy EBRT with 90Gy palladium (Pd)-103 versus 20Gy EBRT with 115Gy Pd-103. The subsequent 20/0 trial randomized patients to the 20Gy arm versus monotherapeutic 125Gy Pd-103. For each trial, univariate Fine-Gray analysis evaluated whether treatment arm was associated with BF for the entire cohort and the unfavorable intermediate risk (UIR) subgroup. For the combined trial cohort, multivariate Fine-Gray analysis evaluated whether BED was associated with BF, while adjusting for clinical factors. ResultsThere were 247 analyzable patients in the 44/20 trial. At a median follow-up of 13.7 years, there were no differences in BF for the entire cohort (sub-distribution hazard ratio (sHR) 0.99; 95% CI: 0.43, 2.276; p = 0.97) or the UIR subgroup (sHR 0.72; 95% CI: 0.25, 2.08; p = 0.55). There were 383 analyzable patients in the 20/0 trial. At a median follow-up of 10.4 years, there were no differences in BF for the entire cohort (sHR 0.42; 95% CI: 0.13-1.80; p = 0.15) or the UIR subgroup (sHR 0.81; 95% CI: 0.16-4.03; p = 0.80). For the combined cohort (630 patients), BED was not associated with BF (1.00; 95% CI: 0.98-1.02; p = 0.88) on multivariate analyses, while adjusting for androgen deprivation therapy utilization, 4-tiered National Comprehensive Cancer Network category, and year of treatment. ConclusionsBrachytherapy monotherapy should be a standard-of-care treatment for clinically localized, intermediate risk prostate cancer, including UIR disease.

The age-adjusted Charlson comorbidity index in acetabular fracture in geriatric acetabular fractures

ObjectiveThis study aimed to analyze factors of comorbidity in older patients with acetabular fracture to know the role of disease in the treatment of this population. MethodsDesign: retrospective cohort study. SettingSingle Level 2 Trauma Center. Patient selection criteriaA prospective database of acetabular fractures in patients over 55 years between January 2011 and January 2021 was studied. The exclusion criteria were age, pathological fracture, associated pelvic or hip fracture, follow-up of less than one year, and not having a computed tomography. Outcome measures and comparisonsPatients were categorised as low (0–2), intermediate (3–4) or high (≥5) risk according to the age-adjusted Charlson comorbidity index (ACCI). The primary outcomes were risk of complications, number of complications and mortality at one year according to the ACCI scale. The difference between the pre-fracture Clinical Frailty Scale (CFS) and the one-year follow-up was also analysed. Descriptive and multivariable regression analyses were performed and ROC curves were constructed. ResultsA total of 119 patients with acetabular fracture were collected. Ninety-eight out of those met inclusion criteria for our study. In regard to ACCI groups, 22% were low-risk, 26% were intermediate-risk, and 52% were high-risk. Statistically significant differences were found according to age, sex, mechanism of injury, treatment type, surgical treatment type, Clinical Frailty Scale (CFS) score, readmissions, complications, and mortality. ROC curves showed an association between ACCI and CFS in terms of complications and mortality, with the exception of unadjusted Charlson comorbidity index. On the multivariable regression analysis, associations were found between ACCI and presence of complications (OR 1.37, 95% CI 1.06–1.77, p=0.015) and mortality (OR 1.32, 95% CI 1.04–1.67, p=0.025) and between CFS and complications (OR 2.01, 95% CI 1.30–3.11, p=0.001) and mortality (OR 1.59, 95% CI 1.08–2.35, p=0.019). No statistical correlation was established between ASA and complications or mortality. ConclusionPresurgical ACCI and CFS scales may serve as a risk assessment method in treatment decision-making for patients with acetabular fracture. An association is observed between patients with a pre-fracture ACCI score ≥5 (high-risk) and a pre-fracture CFS score >4 (mild frailty) and mortality and complications at one year.

A Decade of Contrast-enhanced Mammography: Expanding Screening to Women at Intermediate or High Risk for Breast Cancer.

A Decade of Contrast-enhanced Mammography: Expanding Screening to Women at Intermediate or High Risk for Breast Cancer.

Predictive utility of a combination of the modified caprini risk assessment score and D-dimer for the evaluation and management of lower extremity venous thrombosis after lung cancer surgery

ObjectiveThe objective of this study was to examine the utility of a combination of the modified Caprini score and D-dimer levels for the evaluation and management of lower extremity venous thrombosis following lung cancer surgery. The purpose was to offer insights for developing clinical intervention programs.MethodsThe study sample consisted of 224 patients who underwent surgery for lung cancer at the First Central Hospital of Baoding City. General patient data and D-dimer levels on the first day post-surgery were collected. The modified Caprini risk assessment score was calculated. All patients underwent ultrasonography of the lower limb veins before and after surgery to identify venous thrombosis in the lower limb veins. Differences in lower extremity venous thrombosis and D-dimer levels among patients in various modified Caprini score groups were compared and analyzed.ResultsBased on the modified Caprini risk assessment score, all patients were categorized into three groups: the low-risk, medium-risk, and high-risk groups. The groups did not differ significantly in terms of age, but the differences in the rates of lower extremity venous thrombosis in the low, intermediate, and high-risk Caprini risk groups (16.5%, 19.2%, and 37.1%, respectively) were statistically significant. Out of the total 224 patients, 47 (21%) were diagnosed with venous thromboembolisms post-surgery, and all of them had thrombosis of the intermuscular veins of the lower extremity. The difference in the modified Caprini risk assessment score between patients with and without lower extremity venous thrombosis was statistically significant (P = 0.035), as were the postoperative D-dimer levels (1.28 ± 1.64 vs. 2.69 ± 2.77, respectively; P < 0.05) between these two groups of patients. The modified Caprini risk assessment score showed an association with lower extremity venous thrombosis (r = 0.15, P = 0.56) with an area under the receiver operating characteristic curve (AUC) of 0.59.ConclusionIn this study, we found that combining the modified Caprini risk assessment score with D-dimer measurements enhanced the accuracy of assessing the severity of deep vein thrombosis (DVT). This combination can be beneficial in evaluating thrombosis risk post-lung cancer surgery and holds significant clinical utility.

Genomics in active surveillance and post-prostatectomy patients: A review of when and how to use effectively.

Prostate cancer (PCa) represents a significant health burden globally, ranking as the most diagnosed cancer among men and a leading cause of cancer-related mortality. Conventional treatment methods such as radiation therapy or radical prostatectomy have significant side effects which often impact quality of life. As our understanding of the natural history and progression of PCa has evolved, so has the evolution of management options. Active surveillance (AS) has become an increasingly favored approach to the management of very low, low, and properly selected favorable intermediate risk PCa. AS permits ongoing observation and postpones intervention until definitive treatment is required. There are, however, challenges with selecting patients for AS, which further emphasizes the need for more precise tools to better risk stratify patients and choose candidates more accurately. Tissue-based biomarkers, such as ProMark, Prolaris, GPS (formerly Oncotype DX), and Decipher, are valuable because they improve the accuracy of patient selection for AS and offer important information on the prognosis and severity of disease. By enabling patients to be categorized according to their risk profiles, these biomarkers help physicians and patients make better informed treatment choices and lower the possibility of overtreatment. Even with their potential, further standardization and validation of these biomarkers is required to guarantee their broad clinical utility. Active surveillance has emerged as a preferred strategy for managing low-risk prostate cancer, and tissue-based biomarkers play a crucial role in refining patient selection and risk stratification. Standardization and validation of these biomarkers are essential to ensure their widespread clinical use and optimize patient outcomes.

Tumor size and molecular risk group are associated with differentiated thyroid cancer recurrence

BackgroundThe threshold at which active surveillance can be considered is variable, with some algorithms proposing nonoperative treatment for differentiated thyroid carcinomas ≤2 cm and lobectomy alone for lesions 2.1–4 cm. To inform both decision for and extent of initial surgery, we aim to evaluate whether molecular results can complement tumor size to identify differentiated thyroid carcinomas associated with disease recurrence. MethodsPatients from 2007–2013 and 2017–2021 who had initial thyroidectomy (differentiated thyroid carcinoma size 1–4 cm, clinical N0M0) were included. When available, molecular testing results were categorized into 3 previously described molecular risk groups (low, intermediate, and high). Primary outcome was structural recurrence. ResultsRecurrence was diagnosed in 3.8% of 1,739 patients with differentiated thyroid carcinomas. Preoperative variables including size (1–2 cm vs 2.1–4 cm, P = .43), age >55 years (P = .92), and male sex (P = .31) were not associated with recurrence. Molecular testing results were available for 1,020, and after excluding molecular risk group high-risk differentiated thyroid carcinoma, structural recurrences were associated with molecular risk group intermediate risk (7.2% vs molecular risk group low, 0.7%, P < .001), and most likely in differentiated thyroid carcinoma, which were both 2.1–4 cm and molecular risk group intermediate risk (11.3% vs size 1–2 cm 5.8%, P = .04). ConclusionOverall, structural recurrences for differentiated thyroid carcinomas ≤4 cm were low (<5%) and molecuar testing was the only preoperative variable associated with recurrence. However, when molecular risk group intermediate risk was present, larger tumor size (2.1–4 cm) had a 2-fold greater risk of recurrence compared with tumors 1–2 cm, and size may still be helpful to guide management. When considering de-escalated treatment for the proposed guidelines with a cutoff of 2 cm, initial decision-making may be further optimized with identification of preoperative molecular risk groups.

A metabolome-derived score predicts metabolic dysfunction-associated steatohepatitis and mortality from liver disease

BackgroundMetabolic dysfunction-associated steatohepatitis (MASH) is associated with more than a 10-fold increase in liver-related mortality. However, biomarkers predicting both MASH and mortality are missing. We developed a metabolome-derived prediction score for MASH and examined whether it predicts mortality in Chinese and European cohorts. MethodsThe MASH prediction score was developed using a multi-step machine learning strategy, based on 44 clinical parameters and 250 plasma metabolites measured by proton nuclear magnetic resonance (1H-NMR) in 311 Chinese adults undergoing a liver biopsy. External validation was conducted in a Finnish liver biopsy cohort (n=305). We investigated association of the score with all-cause and cause-specific mortality in the population-based Shanghai Changfeng Study (n=5,893) and the UK Biobank (n=111,673). ResultsA total of 24 clinical parameters and 194 1H-NMR metabolites were significantly associated with MASH in the Chinese liver biopsy cohort. The final MASH score included body mass index, aspartate transaminase, tyrosine, and the phospholipids-to-total lipids ratio in very-low density lipoprotein. The score identified patients with MASH with AUROCs of 0.87 (95% CI, 0.83-0.91) and 0.81 (95% CI, 0.75-0.87) in the Chinese and Finnish cohorts, with high negative predictive values. Participants with a high or intermediate risk of MASH based on the score had a markedly higher risk of MASLD-related mortality than those with a low risk in Chinese (HR, 23.19; 95%CI, 4.80-111.97) and European individuals (HR, 27.80; 95%CI, 15.08-51.26) after 7.4 and 12.6 years of follow-up. The MASH prediction score was superior to the FIB-4 index and the NAFLD Fibrosis Score in predicting MASLD-related mortality. ConclusionThe metabolome-derived MASH prediction score accurately predicts risk of MASH and MASLD-related mortality in both Chinese and European individuals. Impact and implicationsMetabolic dysfunction-associated steatohepatitis (MASH) is associated with more than a 10-fold increase in liver-related death. However, biomarkers predicting not only MASH, but also death due to liver disease, are missing. We established a MASH prediction score based on 44 clinical parameters and 250 plasma metabolites using a machine learning strategy. This metabolome-derived MASH prediction score could accurately identify patients with MASH among both Chinese and Finnish individuals, and it was superior to the FIB-4 index and the NAFLD Fibrosis Score in predicting MASLD-related death in the general population. Thus, the new MASH prediction score is a useful tool for identifying individuals with a markedly increased risk of serious liver-related outcomes among at-risk and general populations.

Histopathologic pattern and molecular risk stratification are associated with prognosis in patients with stage IB lung adenocarcinoma.

The benefit of adjuvant therapy remains controversial in completely resected (R0) stage IB non-small cell lung cancer (NCLSC) patients. In this study, we aimed to explore potential prognostic factors in stage IB NSCLC patients. This study included 215 patients with R0 stage IB lung adenocarcinoma (LUAD) (tumor size: 3-4 cm). DNA sequencing was performed with surgical samples of 126 patients using a panel of 9 driver genes. The molecular risk stratification was assessed by a 14-gene quantitative polymerase chain reaction assay. Among the 215 patients, 67.9% had micropapillary/solid (MIP/SOL)-predominant tumors. Epidermal growth factor receptor (EGFR) mutations were detected in 75 of 126 patients (59.5%). MIP/SOL tumors harbored less common EGFR mutations than the other histologic patterns (50.6% vs. 79.5%, P=0.003). Molecular risk stratification was successfully assessed in 99 patients, of whom 37.4%, 26.3%, and 36.4% were high, intermediate, and low risk, respectively. The MIP/SOL pattern was associated with shorter disease-free survival (DFS) [hazard ratio (HR) =2.16, 95% confidence interval: 1.28-3.67; P=0.01]. The molecular high-risk patients had shorter DFS than the low- (HR =2.93, P=0.01) and intermediate-risk patients (HR =2.35, P=0.06). The prognostic value of molecular risk stratification was also significant in the MIP/SOL subset (median DFS high-risk: 45 months, low and intermediate risk: not reached; P=0.03). Our study showed that both the MIP/SOL pattern and molecular high-risk category were adverse prognostic factors in stage IB NSCLC patients. Our results suggest that combining histologic classification and molecular risk stratification may help to identify the subset of patients with poor prognosis.

HYGIENE DES DISPOSITIFS MEDICAUX REUTILISABLES DANS LA GESTION DES VOIES AERIENNES EN ANESTHESIE AU CHUD/ BORGOU-ALIBORI

Introduction :Nosocomial infection is a priority concern for hospitals. The aim of this study was to investigate the hygiene of reusable medical devices (DMR) used in anesthesia at CHUD-B/A. Methods :The study was observational, cross-sectional, descriptive and analytical. It surveyed nursing staff in the anesthesia department of CHUD Borgou/Alibori. Sampling was non-random, with a census of all staff. Data analysis was performed using IBM SPSS Statistics 21 software. Observations in the study were presented in proportions for qualitative variables and quantitative data using central tendency parameters such as mean with standard deviation, median as appropriate, mode and extremums. Results :A total of 14 caregivers were surveyed. Intermediate risks were related to semi-critical materials, according to 64.3% of subjects. Knowledge of DMR processing steps was affirmed by 92.2% of staff. Decontamination followed by cleaning and rinsing was confirmed by 84.6% of respondents. It was observed that equipment was immersed in a small jar containing a small volume of non-renewed decontamination solution, that there was no decontamination protocol, that hand hygiene was observed in 25 cases, and that gloves were worn in 30 cases. Conclusion:The absence of a DMR management protocol is apparent. Device hygiene needs to be improved. The development of a protocol for DMR treatment and the promotion of single-use equipment are necessary.

Imetelstat (Rytelo) for Myelodysplastic Syndromes

The FDA has approved imetelstat (Rytelo – Geron), a first-in-class telomerase inhibitor, for treatment of low- to intermediate-1 risk myelodysplastic syndromes (MDS) in adults with transfusion-dependent anemia requiring 4 or more red blood cell (RBC) units over 8 weeks who have not responded to, are no longer responding to, or are ineligible for erythropoiesis-stimulating agents (ESAs).

Consider or not consider: the unsolved question on the use of radioactive iodine for differentiated thyroid cancer with low to intermediate risk of recurrence.

Surgery stands as the cornerstone treatment for differentiated thyroid cancer (DTC). After surgery, radioactive iodine (RAI) administration is primarily recommended for high-risk patients and commonly employed to address residual disease or mitigate the risk of recurrence. However, the optimal application of RAI in cases categorized as low to intermediate risk is still uncertain. This study aims to assess the indication of post-surgical RAI treatment specifically in patients diagnosed with DTC falling within the low to intermediate risk category for recurrent disease. retrospective analysis of consecutive patients with DTC falling within the low to intermediate risk category for recurrence and diagnosed between 2009-2015. Patients were categorized into either treated or untreated with RAI. Treatment effect was assessed by the inverse-probability weighted regression adjustment (IPWRA), by balancing the distribution of factors influencing outcome and treatment assignment. after surgery, 328 patients (69.9%) were treated with RAI while 141 (30.1%) were left untreated. Across the entire cohort, 44 individuals (9.4%) displayed biochemical or structural disease after a median time of 17.5 months following diagnosis. Recurrent disease was more prevalent in patients who underwent RAI treatment compared to those untreated (12.5% vs 2.1%, respectively, p < 0.001). Factors independently associated with recurrent disease, identified through multivariate logistic regression analysis, included lymph node metastases (pN1) (OR = 4.07; 95% CI 1.84-8.97), male sex (OR = 2.71; 95% CI 1.31-5.59), tumor size (OR = 1.03; 95% CI 1.00-1.06), and microscopic extrathyroidal extension (OR = 2.36; 95% CI 1.15-4.81). IPWRA analysis revealed that the occurrence of recurrent disease was 9.6% (95% CI = 6.3-12.9) in RAI-treated patients and 15.9% (95% CI = 11.1-20.71) in untreated patients (p = 0.021). As a consequence, if all patients underwent RAI treatment, the estimated risk of recurrence would be reduced by 42% (RR = 0.58; 95% CI = 0.35-0.91, p = 0.018). The greatest benefit was observed in patients with 2 intermediate risk factors. These results suggest that treatment with RAI in low to intermediate DTC can reduce the risk of recurrence in selected patients. However, definitive answers regarding whether to consider RAI therapy for this category of patients can only be attained through prospective clinical trials. Up to date these results recommend a meticulous assessment of tumor characteristics at diagnosis to guide the decision regarding RAI administration.

Comprehensive Risk Assessment in Patients With Pulmonary Arterial Hypertension Referred for Lung Transplantation.

Whether comprehensive risk assessment predicts post-referral outcome in patients with pulmonary arterial hypertension (PAH) referred for lung transplantation (LT) in Japan is unknown. We retrospectively analyzed 52 PAH patients referred for LT. Risk status at referral was assessed using 3- and 4-strata models from the 2022 European Society of Cardiology and European Respiratory Society guidelines. The 3-strata model intermediate-risk group was further divided into 2 groups based on the median proportion of low-risk variables (modified risk assessment [MRA]). The primary outcome was post-referral mortality. During follow-up, 9 patients died and 13 patients underwent LT. There was no survival difference among 3-strata model groups. The 4-strata model classified 33, 16, and 3 patients as low intermediate, high intermediate, and high risk, respectively. The 4-strata model identified high-risk patients with a 1-year survival rate of 33%, but did not discriminate survival between the intermediate-risk groups. The MRA classified 15, 28, 8, and 1 patients as low, low intermediate, high intermediate, and high risk, respectively. High intermediate- or high-risk patients had worse survival (P<0.001), with 1- and 3-year survival rates of 64% and 34%, respectively. MRA high intermediate- or high-risk classification was associated with mortality (hazard ratio 12.780; 95% confidence interval 2.583-63.221; P=0.002). Patients classified as high intermediate or high risk by the MRA after treatment should be referred for LT.

Coronary artery calcification detected on low-dose computed tomography in high-risk participants of an Australian lung cancer screening program: A prospective observational study.

Coronary artery calcification (CAC) is a frequent additional finding on lung cancer screening (LCS) low-dose computed tomography (LDCT). Cardiovascular disease (CVD) is a major cause of death in LCS participants. We aimed to describe prevalence of incidental CAC detected on LDCT in LCS participants without prior history of coronary artery disease (CAD), evaluate their CVD risk and describe subsequent investigation and management. Prospective observational nested cohort study including all participants enrolled at a single Australian site of the International Lung Screen Trial. Baseline LDCTs were reviewed for CAC, and subsequent information collected regarding cardiovascular health. 5-year CVD risk was calculated using the AusCVD risk calculator. 55% (226/408) of participants had CAC on LDCT and no prior history of CAD, including 23% with moderate-severe CAC. Mean age of participants with CAC was 65 years, 68% were male. 53% were currently smoking. Majority were high risk (51%) or intermediate risk (32%) of a cardiovascular event in 5 years. 21% of participants were re-stratified to a higher CVD risk group when CAC detected on LCS was incorporated. Only 10% of participants with CAC received lifestyle advice (only 3% currently smoking received smoking cessation advice). 80% of participants at high-risk did not meet guideline recommendations, with 47% of this group remaining without cholesterol lowering therapy. LCS with LDCT offers the potential to identify and communicate CVD risk in this population. This may improve health outcomes for high-risk LCS participants and further personalize management once screening results are known.

Efficacy of postoperative radioactive iodine therapy for patients with low and intermediate risk papillary thyroid carcinoma.

This study aimed to evaluate the efficacy of postoperative radioactive iodine (RAI) and its impact on recurrence rates and survival benefits in low- to intermediate-risk papillary thyroid carcinoma (PTC). This retrospective study involved the examination of 1286 patients diagnosed with low- to intermediate-risk PTC who underwent total thyroidectomy with or without neck dissection, supplemented with postoperative RAI therapy or not between the years 2000 and 2021. From the patient pool, 589 (45%) were classified as low-risk and 697 (55%) as intermediate-risk according to the 2015 American Thyroid Association guidelines. Among the low-risk group, 375 (63.7%) underwent postoperative RAI, while in the intermediate-risk group, 566 (82.2%) underwent the procedure. The overall survival and disease-free survival rates were not statistically different between the groups that received RAI and those that did not, in both the low- and intermediate-risk categories. In a subgroup analysis, within the intermediate-risk category, postoperative RAI was significantly correlated with decreased recurrence in two subgroups: patients over 55 years with pN1b disease (hazard ratio 0.043, 95% confidence interval 0.004-0.500, p = 0.012) and patients over 55 years with five or more metastatic lymph nodes (hazard ratio 0.060, 95% confidence interval 0.005-0.675, p = 0.023). Our findings suggest that, while post-total thyroidectomy RAI does not substantially influence recurrence or survival rates in most low-risk and intermediate-risk PTC patients, it may be beneficial in specific subgroups, particularly patients over 55 with pN1b disease or those presenting with five or more metastatic lymph nodes.

Sutureless Aortic Prosthesis Valves versus Transcatheter Aortic Valve Implantation in Intermediate Risk Patients with Severe Aortic Stenosis: A Literature Review.

Aortic stenosis remains the most frequently occurring valvular pathology in the elderly population of Western countries. According to the latest guidelines, the therapeutic choice of aortic stenosis depends on the age of the patient (<75 years or >75 years) and the risk class (STS-Prom/Euroscore II < o >4%). Therefore, if the surgical indication is clear in young and low-risk patients and percutaneous treatment is the gold standard in older and high-risk patients, the therapeutic choice is still debated in intermediate-risk patients. In this group of patients, aortic valve stenosis treatment depends on the patient's global evaluation, the experience of the center, and, no less importantly, the patient's will. Two main therapeutic options are debated: surgical aortic valve replacement with sutureless prosthesis versus transcatheter aortic valve implantation. In addition, the progressive development of mininvasive techniques for aortic valve surgery (right-anterior minithoracotomy) has also reduced the peri- and post-operative risk in this group of patients. The purpose of this review is to compare sutureless aortic valve replacement (SuAVR) versus TAVI in intermediate-risk patients with severe aortic stenosis.

21-gene recurrence score predictive of the benefit of postoperative radiotherapy after breast-conserving surgery for elderly patients with T1N0 and luminal breast cancer.

To assess the predictive value of the 21-gene recurrence score (RS) on the survival outcomes of postoperative radiotherapy (PORT) in elderly patients with T1N0 luminal breast cancer after breast-conserving surgery. We retrospectively included patients aged ≥ 70years and diagnosed with T1N0 luminal BC between 2004 and 2015 using the data from the Surveillance, Epidemiology, and End Results. The RS groups were categorized using the TAILORx criteria as follows: low risk (RS < 11) (LR), intermediate risk (RS 11-25) (IR), and high risk (RS > 25) (HR). Kaplan-Meier analysis, propensity score matching (PSM), and Cox proportional hazards analysis were used for statistical analysis. We included 5901 patients in the analysis. Of the patients, 4492 (76.1%) underwent PORT, while 1409 (23.9%) did not receive PORT. There were 1588 (26.9%), 3613 (61.2%), and 700 (12.0%) patients classified as LR, IR, and HR, respectively. There were 1182 (74.4%), 2773 (76.8%), and 537 (76.7%) patients in the LR, IR, and HR groups receiving PORT, respectively (P = 0.182). A total of 1353 pairs of patients were completely matched using PSM. PORT was independently associated with better overall survival (OS) (P < 0.001) and breast cancer-specific survival (BCSS) (P = 0.015) in the entire cohort. The sensitivity analyses showed that the receipt of PORT was not associated with OS (P = 0.887) and BCSS (P = 0.861) in the LR group. However, the receipt of PORT was associated with OS (P < 0.001) and BCSS in the IRHR group (P = 0.026). Our study highlights the possible role of the 21-gene RS in predicting the survival outcomes of PORT following BCS in elderly patients with T1N0 luminal breast cancer.

Corrected generalized cross-validation for finite ensembles of penalized estimators

Abstract Generalized cross-validation (GCV) is a widely used method for estimating the squared out-of-sample prediction risk that employs scalar degrees of freedom adjustment (in a multiplicative sense) to the squared training error. In this paper, we examine the consistency of GCV for estimating the prediction risk of arbitrary ensembles of penalized least-squares estimators. We show that GCV is inconsistent for any finite ensemble of size greater than one. Towards repairing this shortcoming, we identify a correction that involves an additional scalar correction (in an additive sense) based on degrees of freedom adjusted training errors from each ensemble component. The proposed estimator (termed CGCV) maintains the computational advantages of GCV and requires neither sample splitting, model refitting, or out-of-bag risk estimation. The estimator stems from a finer inspection of the ensemble risk decomposition and two intermediate risk estimators for the components in this decomposition. We provide a non-asymptotic analysis of the CGCV and the two intermediate risk estimators for ensembles of convex penalized estimators under Gaussian features and a linear response model. Furthermore, in the special case of ridge regression, we extend the analysis to general feature and response distributions using random matrix theory, which establishes model-free uniform consistency of CGCV.

Behavioral risk factors and socioeconomic inequalities in ischemic heart disease mortality in the United States: A causal mediation analysis using record linkage data.

Ischemic heart disease (IHD) is a major cause of death in the United States (US), with marked mortality inequalities. Previous studies have reported inconsistent findings regarding the contributions of behavioral risk factors (BRFs) to socioeconomic inequalities in IHD mortality. To our knowledge, no nationwide study has been conducted on this topic in the US. In this cohort study, we obtained data from the 1997 to 2018 National Health Interview Survey with mortality follow-up until December 31, 2019 from the National Death Index. A total of 524,035 people aged 25 years and older were followed up for 10.3 years on average (SD: 6.1 years), during which 13,256 IHD deaths occurred. Counterfactual-based causal mediation analyses with Cox proportional hazards models were performed to quantify the contributions of 4 BRFs (smoking, alcohol use, physical inactivity, and BMI) to socioeconomic inequalities in IHD mortality. Education was used as the primary indicator for socioeconomic status (SES). Analyses were performed stratified by sex and adjusted for marital status, race and ethnicity, and survey year. In both males and females, clear socioeconomic gradients in IHD mortality were observed, with low- and middle-education people bearing statistically significantly higher risks compared to high-education people. We found statistically significant natural direct effects of SES (HR = 1.16, 95% CI: 1.06, 1.27 in males; HR = 1.28, 95% CI: 1.10, 1.49 in females) on IHD mortality and natural indirect effects through the causal pathways of smoking (HR = 1.18, 95% CI: 1.15, 1.20 in males; HR = 1.11, 95% CI: 1.08, 1.13 in females), physical inactivity (HR = 1.16, 95% CI: 1.14, 1.19 in males; HR = 1.18, 95% CI: 1.15, 1.20 in females), alcohol use (HR = 1.07, 95% CI: 1.06, 1.09 in males; HR = 1.09, 95% CI: 1.08, 1.11 in females), and BMI (HR = 1.03, 95% CI: 1.02, 1.04 in males; HR = 1.03, 95% CI: 1.02, 1.04 in females). Smoking, physical inactivity, alcohol use, and BMI mediated 29% (95% CI, 24%, 35%), 27% (95% CI, 22%, 33%), 12% (95% CI, 10%, 16%), and 5% (95% CI, 4%, 7%) of the inequalities in IHD mortality between low- and high-education males, respectively; the corresponding proportions mediated were 16% (95% CI, 11%, 23%), 26% (95% CI, 20%, 34%), 14% (95% CI, 11%, 19%), and 5% (95% CI, 3%, 7%) in females. Proportions mediated were slightly lower with family income used as the secondary indicator for SES. The main limitation of the methodology is that we could not rule out residual exposure-mediator, exposure-outcome, and mediator-outcome confounding. In this study, BRFs explained more than half of the educational differences in IHD mortality, with some variations by sex. Public health interventions to reduce intermediate risk factors are crucial to reduce the socioeconomic disparities and burden of IHD mortality in the general US population.

Psychological impact of Placenta Accreta Spectrum disorders (PAS) and risk of Post-Traumatic Stress Disorder (PTSD): A cross-sectional study

ObjectivePlacenta Accreta Spectrum disorders (PAS) are a group of obstetric complications with an increasing incidence. The high maternal and neonatal morbidity and mortality associated with PAS leads to concerns about the negative psychological impact, and even the risk of developing Post-Traumatic Stress Disorder (PTSD). The aim of this study was to assess the psychological impact of PAS diagnosis and intervention during pregnancy and postpartum and its potential association with PTSD.STUDY DESIGN: A cross-sectional study was conducted, including cases of PAS FIGO grade 2 and 3 treated at University Hospital Center São João, between 2010–2023. Only cases with histopathological confirmation after peripartum hysterectomy were included. Data were obtained from electronic medical records (Sclinic® and Obscare®). The impact of Event Scale – Revised (IES-R), a validated questionnaire, was applied, after surgery for PAS, to assess the psychological impact of PAS diagnosis and treatment. ResultsFourteen cases of PAS were identified. The mean maternal age was 36.8 years. Approximately 86 % of cases had antenatal suspicion. The mean gestational age at delivery was 34 weeks. Of the 14 women, only 11 responded to the request to participate in the study (7 interviewed in person and 4 remotely). Four women had IES-R scores indicative of high risk of PTSD (IES-R>33 points), one had an intermediate risk (IES-R between 24–32 points), and 6 fell into the low-risk category. The mean score was 22.4 points. The analysis of IES-R results by clusters showed higher scores in the intrusion category, which relates to intrusive and unwanted thoughts, images and memories. ConclusionGiven the high morbidity and mortality described in women with PAS, the risk of PTSD should be acknowledged, motivating early intervention to prevent the development of severe and potentially chronic symptoms. Supportive measures and psychiatric and/or psychological follow-up should be promptly implemented, ideally by multidisciplinary teams.