Survival Advantage Research Articles

Does T1c–2N0–1M0 triple negative breast cancer derive a benefit from neoadjuvant chemotherapy?

ObjectivesAlthough neoadjuvant chemotherapy (NCT) is a standard approach for operable triple negative breast cancer (TNBC), the potential risks brought by it should also be noticed. Is the expanding indication of NCT to T1cN0M0 population appropriate? We conducted an investigation to compare the long-term survival of small tumor TNBC between NCT and adjuvant chemotherapy (ACT).MethodsFor this propensity-matched analysis, we used data from Surveillance, Epidemiology, and End Results (SEER) database. We enrolled 1183 cases with NCT and 2550 cases with ACT who are AJCC clinical T1c–T2 N0–N1, diagnosed with invasive triple-negative breast cancer, from 2016 to 2017. The propensity score matching was utilized to minimize baseline characteristics bias. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated by the Cox proportional hazard regression model.ResultsCompared with patients receiving ACT, patients with NCT in this study presented a higher proportion of younger age, T2 stage, N1 stage, and underwent more mastectomy. Multivariate analysis in matched patients showed that NCT had no significant survival benefit compared with ACT in T1c–2N0–1M0 TNBC patients. Stratified analyses by T stage and N stage demonstrated NCT mainly presented a survival advantage in patients with N1 stage. Further investigation found that NCT didn’t improve BCSS (HR, 0.472; 95% CI 0.135–1.647; P = 0.239) and OS (HR, 0.392; 95% CI 0.147–1.047; P = 0.062) for patients with T1cN0M0 TNBC; however, it was associated with improved OS (HR, 1.951; 95% CI 1.003–3.797; P = 0.049) only for patients with T2N1M0 TNBC.ConclusionsIn this study, we did not find any profit brought by NCT in the stage I and stage IIa cohorts, but even more unfavorable outcomes appeared in the T1cN0M0 cohort. Therefore, whether the candidates of NCT should be extended to T1cN0M0 still need to be cautious.

An Analysis of 24-Hour Survival Based on Arrival by Atypical Ground Transport Versus Ground Emergency Medical Services

Objectives Studies comparing police, privately owned vehicle (POV), and ground Emergency Medical Services (GEMS) trauma transports reveal mixed results. It remains unclear whether using nonstandard transport methods may be beneficial in the setting of certain injuries. We sought to determine 24-h survival after transport by police or POV when compared to GEMS. Methods We analyzed data from the Trauma Quality Improvement Program datasets from 2020 to 2022 for patients arriving from scene by POV, police, or GEMS. The primary outcome was 24-h survival. Multivariable logistic regression models were used to adjust for confounders. Further stratification was performed by mechanism. We used abbreviated Injury Severity Score (ISS) by body region to assess those with and without penetrating torso trauma. Results Patients arriving by POV had a lower median age than those arriving by GEMS and a higher proportion of pediatric patients. This group exhibited a lower incidence of blunt trauma but a higher incidence of penetrating trauma, along with fewer serious injuries across all body regions. Across all adjusted models, arrival by POV was associated with higher odds of 24-h survival, except for cases of penetrating torso trauma among pediatric patients. Patients arriving by police also had a lower median age but a reduced proportion of pediatric patients. This group showed a higher proportion of penetrating trauma and serious injuries to the thorax and abdomen. Police arrivals with blunt trauma had higher odds of 24-h survival, while those with penetrating trauma had lower odds of 24-h survival, a pattern consistent when stratifying by ISS greater than 15. Conclusions This study highlights a survival advantage for trauma patients transported by POV compared to GEMS. Limitations include a lack of prehospital transport time and intervention data. While police transport showed improved survival for blunt trauma, it was associated with worse outcomes for penetrating trauma. These findings suggest that nontraditional transport methods may be beneficial in certain scenarios. Future research should aim to refine transport protocols, investigate the impact of nontraditional methods on transport time, and better understand the impact of prehospital interventions on patient outcomes.

Comparison of treatment regimens for unresectable stage III epidermal growth factor receptor (EGFR)mutant non-small cell lung cancer.

Durvalumab after chemoradiotherapy (CRT) failed to bring survival benefits to patients with epidermal growth factor receptor (EGFR) mutations in PACIFIC study ( evaluating durvalumab in patients with stage III, unresectable NSCLC who did not have disease progression after concurrent chemoradiotherapy). We aimed to explore whether locally advanced inoperable patients with EGFR mutations benefit from tyrosine kinase inhibitors (TKIs) and the optimal treatment regimen. We screened the PubMed, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases from January 1, 2000 to December 31, 2022 and performed a meta-analysis based on a Bayesian framework, with progression-free survival (PFS) and overall survival (OS) as the primary endpoints. A total of 1156 patients were identified in 16studies that included 6 treatment measures, including CRT, CRT followed by durvalumab (CRT-Durva), TKI monotherapy, radiotherapy combined with TKI (RT-TKI), CRT combined with TKI (CRT-TKI), and TKI combined with durvalumab (TKI-Durva). The PFS after the TKI-containing treatments was significantly longer than after the TKI-free treatments (hazard ratio [HR]=0.37, 95% confidence interval [CI],0.20-0.66). The PFS of TKI monotherapy was significantly longer than CRT (HR=0.66, 95% CI, 0.50-0.87) but shorter than RT-TKI (HR=1.78, 95% CI,1.17-2.67). Furthermore, the PFS of RT-TKI or CRT-TKI were both significantly longer than that of CRT or CRT-Durva. RT-TKI ranked first in the Bayesian ranking, with the longest OS (60.8months, 95% CI=37.2-84.3 months) and the longest PFS (21.5months, 95% CI,15.4-27.5 months) in integrated analysis. For unresectable stage III EGFR mutant NSCLC, RT and TKI are both essential. Based on the current evidence, RT-TKI brings the best survival advantage, while CRT-TKI needs further estimation. Large randomized clinical trials are urgently needed to explore the appropriate application sequences of TKI, radiotherapy, and chemotherapy. PROSPERO; https://www.crd.york.ac.uk/PROSPERO/; No. CRD42022298490.

Phenotypic upregulation of hexocylceramides and ether-linked phosphocholines as markers of human extreme longevity.

Centenarians and their relatives possess a notable survival advantage, with higher longevity and reduced susceptibility to major age-related diseases. To date, characteristic omics profiles of centenarians have been described, demonstrating that these individuals with exceptional longevity regulate their metabolism to adapt and incorporate more resilient biomolecules into their cells. Among these adaptations, the lipidomic profile stands out. However, it has not yet been determined whether this lipidomic profile is specific to centenarians or is the consequence of extreme longevity genetics and is also present in centenarians' offspring. This distinction is crucial for defining potential therapeutic targets that could help delay the aging process and associated pathologies. We applied mass-spectrometry-based techniques to quantify 569 lipid species in plasma samples from 39 centenarians, 63 centenarians' offspring, and 69 noncentenarians' offspring without familial connections. Based on this profile, we calculated different indexes to characterize the functional and structural properties of plasma lipidome. Our findings demonstrate that extreme longevity genetics (centenarians and centenarians' offspring) determines a specific lipidomic signature characterized by (i) an enrichment of hexosylceramides, (ii) a decrease of specific species of ceramides and sulfatides, (iii) a global increase of ether-PC and ether-LPC, and (iv) changes in the fluidity and diversity of specific lipid classes. We point out the conversion of ceramides to hexosylceramides and the maintenance of the levels of the ether-linked PC as a phenotypic trait to guarantee extreme longevity. We propose that this molecular signature is the result of an intrinsic adaptive program that preserves protective mechanisms and cellular identity.

Race and ethnicity dynamics in survival to 100 years in the United States.

After age 85, the U.S. non-Hispanic Black population mortality rate becomes less than that of the White population (called the Black-White mortality crossover). It is not known how this survival advantage compares to Asian and Hispanic groups, and whether differences persist to age 100+ years. The U.S. period life table data were extracted to obtain life expectancy at birth and at ages 70, 85, and 100 years according to year, sex, and race and ethnicity. Age-specific death rates and adult modal age at death were calculated. We computed period probabilities of survival to age 100, from ages 70, 80, and 90. Pseudo-birth cohort calculations were undertaken to enable comparison with period-based results. In 2019, the Black-White mortality crossover occurred at 86-88 years and persisted at ages 100 and 100+. Life expectancies at age 100 for non-Hispanic Black, Hispanic, and Asian populations were similar and were significantly greater than the non-Hispanic White population. From 2006 to 2019, the probability of survival from 70 and 80 years to age 100 was highest for the Hispanic population, followed by non-Hispanic Black and then non-Hispanic White populations. Probability of survival from age 90 to 100 years was similar for all but the non-Hispanic White population, which had a comparatively lower probability of survival. When Asian population data became available in 2019, this population had the highest probability of survival to age 100, starting from ages 70, 80, and 90 years. Pseudo-cohort results displayed patterns consistent with those observed over calendar years. Race- and ethnicity-based variation in mortality between ages 85 and 100+ years suggests differences in environmental and possibly genetic influences upon risk for exceptional longevity.

Autologous non-myeloablative hematopoietic stem cell transplantation for diffuse cutaneous systemic sclerosis: identifying disease risk factors for toxicity and long-term outcomes in a prospective, single-arm trial.

Two randomized trials for patients with diffuse systemic sclerosis (SSc) demonstrated an overall survival (OS) and event-free survival (EFS) advantage of autologous hematopoietic stem cell transplantation (AHSCT) using CD34+ selected peripheral blood stem cells (PBSC) compared to monthly cyclophosphamide. We asked if an unmodified PBSC graft followed by maintenance mycophenolate mofetil (MMF) after AHSCT, instead of CD34+ selected graft, could provide comparable AHSCT outcomes. 20 patients with high-risk SSc were enrolled in a prospective, single-arm trial with cyclophosphamide 200 mg/kg and horse anti-thymocyte globulin (CY200/ATG), followed by unmanipulated autologous PBSC, then MMF maintenance starting at 2 months after AHSCT. Point estimates of OS and EFS at 5 years after AHSCT were 85% (95% CI, 60.4%-94.9%) and 75% (95% CI, 50%-88.7%), respectively. Median follow-up was 7.5 years (range, 5.6-11.6) after transplant for living patients. Eight patients (40%) required intensive care unit treatment early after transplant. Early transplant-related mortality occurred in 2 patients (10%). Five patients developed relapse/progression of SSc after AHSCT. Four of 9 patients with anti-RNA polymerase-III antibody had both prior scleroderma renal crisis and the lowest quartile of estimated glomerular filtration rate (eGFR) upon study entry; all 4 patients developed prolonged organ failure/death early post-transplant. We observed favorable OS and EFS after AHSCT for SSc patients, using CY200/ATG, unmanipulated PBSC and MMF post-transplant maintenance, that was comparable to trials with CD34+ graft selection. We identified a possible risk factor, pretransplant low eGFR, for adverse outcome after AHSCT.

The impact of lymph node involvement on adjuvant chemotherapy and survival in patients with resected invasive intraductal papillary mucinous neoplasm: a propensity score matching study based on SEER database and external validation

Background: Limited knowledge and guidelines exist for invasive intraductal papillary mucinous neoplasm (IPMN). This study aims to explore the significance of lymph node involvement on adjuvant chemotherapy (ACT) for invasive IPMN. Materials and Methods: Patients diagnosed with invasive IPMN were selected from both the SEER database and our hospital. Kaplan-Meier analysis, Cox proportional hazards model, and propensity score matching (PSM) were employed in this study. Results: In the SEER group, multivariate analysis involving 775 patients revealed that several factors including age, tumor differentiation, AJCC-T staging, N staging, and TNM stage significantly influenced overall survival (OS) and cancer-specific survival (CSS). Turning to the Zhongshan Hospital group (ZS group), which had 94 recruited patients, multivariate analysis for OS, CSS, and recurrence-free survival (RFS) showed that AJCC N staging emerged as the most significant risk factor, with HR values of 4.664, 4.955, and 3.175, respectively. In subgroup analysis, ACT provided survival advantages for patients with positive lymph node metastasis (LNM). In a PSM analysis focused on patients with positive LNM, the comparison revealed that ACT emerged as a critical factor influencing both OS and CSS (both p<0.005). Especially, these patients younger than 60 year old, or those with AJCC-T2-N+ staging were found to get apparently benefit from ACT as revealed by our subgroup interaction analysis. Conclusion: LNM plays a pivotal role in the management of invasive IPMN patients underwent surgery, and ACT might be a beneficial therapeutic option for individuals concurrent with LNM, particularly among those younger than 60 year old, or with AJCC-T2-N+ staging.

A retrospective analysis of clinical features, management and outcomes in dogs and cats with Eastern Brown Snake envenomation (2016-2022).

Australian Eastern brown snakes (Pseudonaja textilis) can cause venom-induced consumptive coagulopathy (VICC) in envenomated dogs and cats due to toxin-induced consumption of clotting factors. The objective of this study was to describe presenting clinical signs, prevalence of VICC and haemorrhage, VICC resolution timelines and patient outcomes in a population of dogs and cats with Eastern brown snake envenomation (EBSE). Data from dogs and cats presenting with EBSE were retrospectively evaluated. Univariable and multivariable analyses were performed to test predictor variable effects on outcomes. Animals who were euthanased for financial reasons on presentation were excluded from treatment and outcome analysis. Two-hundred and forty dogs and 98 cats were included. On presentation, 66% (159/240) of dogs had lower motor neuropathy (LMN), 31% (74/240) had preparalytic collapse and 30% (72/240) had signs of haemorrhage. In cats, 94% (92/98) had LMN, and only 5% (5/98) had haemorrhage. Ninety-two percent of dogs (209/226) and cats (81/88) were diagnosed with VICC on presentation and median time to normalisation of coagulation tests was 24 hours. Median hospitalisation length was 1.5 days for dogs (lower quartile [LQ]-upper quartile [UQ]: 1.0-3.0) and 2 days for cats (LQ - UQ: 1.0-2.5). Dogs presenting with LMN and no history of preparalytic collapse had significantly longer hospitalisation times (median 2.25 vs. 1.0 days, P-value <0.001; median 2.0 vs. 1.0 days, P-value <0.001 respectively). Odds of survival was lower in dogs with LMN (odds ratio [OR]: 0.23) and in the pooled multivariable analysis of dogs and cats with haemorrhage (OR: 0.39). The administration of antivenom overall was found to confer a survival advantage; however analysis failed to show increased odds of survival with administration of more than 4000 units. Overall, 89% (187/210) of dogs and 75% (58/77) of cats survived to discharge.

Dichloroacetate and chloroquine in combination with arsenite suppress ROS-induced oral squamous cell carcinoma (OSCC) development and improve BALB/c mice survival.

Oral squamous cell carcinoma (OSCC) is a disabling tumor with poor response to chemotherapy. Here, we sought to explore a new chemotherapeutic approach based on a combined induction of cytotoxic ROS and targeting of autophagy and aerobic glycolysis as central contributors to OSCC carcinogenesis and chemoresistance. To this end, tongue OSCC was generated in BALB/c mice using 4NQO. Treatment of mouse-derived OSSC explants with NaAsO2 resulted in a strong inhibition of MTT activity and Bcl-2 and Ki-67 expression. The addition of chloroquine (CQ) and dichloroacetate (DCA) to arsenite, resulted in additive inhibitory effects on Bcl-2 and Ki-67 expression. Whereas NaAsO2 alone inhibited aerobic glycolysis (LDHA), it also alleviated autophagy (LC3B) and ROS levels (MDA). DCA improved NaAsO2-dependent inhibition of aerobic glycolysis. CQ addition to arsenite, suppressed autophagy without affecting the Warburg effect. NaAsO2 combination with CQ and DCA improved the oxidative status balance by boosting anti-oxidative CAT and SOD and controlling pro-oxidant MDA activity. The administration of the combo to 4NQO-mice resulted in a significant survival advantage over the control group (90% vs. 35% survival at week 32, p< 0.02; HR (log-rank) = 0.166, CI 95% 0.03-0.73). This effect was accompanied by a significant increase in mice's mean body weight (p< 0.009). Contrarily to the control, administration of the combo resulted in the absence of progression towards severe dysplasia and OSCC and an overrepresentation of low/mild dysplasia events (100%). Interestingly, signs of hepatocellular and renal toxicity following combo administration were limited in comparison to control. Taken together, these results suggest that NaAsO2 combined with CQ and DCA may constitute an interesting alternative to eliminating chemo-resistant OSSC tumors by inhibiting aerobic glycolysis and autophagy and controlling ROS generation. In vivo, the drugs may provide a survival advantage by inhibiting tumor development.

Structure-function relationship of PE11 esterase of Mycobacterium tuberculosis with respect to its role in virulence

The lipolytic enzymes of Mycobacterium tuberculosis play a critical role in immunomodulation and virulence. Among these proteins, PE11 which also belongs to the PE/PPE family, is the smallest (∼10.8 kDa) and play a significant role in cell wall remodelling and virulence. PE11 is established to be an esterase, but its enzymatic and structural properties are not yet characterized. In this study, using homology modelling we deduced the putative structure which shows the presence of both α-helix and β-sheet structures which is in close agreement with that observed by CD spectra of the purified protein. PE11 was found to contain a Gx3Sx4G motif homologous to canonical ‘GxSxG’ motif present in many serin hydrolases. The catalytic triad appears to be located within this motif as substitution of Serine26 and Glycine31 residues abrogated its enzymatic activity. Gel-filtration chromatography data indicate that PE11 possibly exists as dimer and tetramer showing positive cooperativity for binding its substrates. In addition, PE11 esterase activity was found to be critical for cell wall remodelling, antibiotic resistance and conferring survival advantages to M. tuberculosis. Our data suggest that PE11 can be targeted for designing potential therapeutic strategies.

Lung Transplant Outcomes in Recipients of Advanced Age: Are Two Always Better Than One?

Lung transplantation has become more common in patients aged 65 years and older. We aimed to examine outcomes across age groups and identify risk factors for decreased survival. United Network for Organ Sharing data for all primary lung transplants from 1/1/2006 to 3/8/2023 was retrospectively reviewed. Impact of recipient age on survival was analyzed. Of the 33,644 lung transplant recipients that were identified, 23,125 (69%), 7,270 (21%), 2,895 (9%), and 354 (1%) were aged 12-64, 65-69, 70-74, and 75-79 years, respectively. Older patients underwent single lung transplantation more often (12-64: 19%, 65-69: 41%, 70-74: 57%, 75-79: 75%, p<0.001). Median survival was higher in bilateral compared to single lung transplant in all groups except 75-79 (12-64: 7.6 vs. 5.6, p < 0.001; 65-69: 5.8 vs. 4.8, p < 0.001; 70-74: 5.0 vs. 3.9, p < 0.001; 75-79: 4.0 vs. 3.9 years, p = 0.919). Prior cardiac surgery was associated with increased hazard of death (HR: 1.27, 95% CI, 1.14-1.41, p<0.001) and higher likelihood of receiving a single lung transplant with older age (12-64 years: 45.3%, 65-79 years: 71.0%, p < 0.001). Bilateral lung transplantation offers a survival advantage over single lung transplantation in recipients up to 74 years of age. Recipients aged 75 to 79 have poor long-term survival. Prior cardiac surgery is associated with worse long-term survival, necessitating careful patient selection, especially in older patients being offered a single lung transplant.

Multigene Copy Number Alteration Risk Score Biomarker-Based Enrichment Study Designs in Metastatic Castrate-Resistant Prostate Cancer.

A composite multigene risk score derived from tumor-biology alterations specific to metastatic castrate-resistant prostate cancer (mCRPC) state was evaluated as a classifier to design biomarker-based enrichment clinical trials. A plasma cell-free DNA copy number alteration risk score based on alterations in 24 genes was simulated to develop a biomarker classifier-based clinical trial design enriched for high-risk patients to detect a survival advantage of a novel treatment (hazard ratio of 0.70 with 80% power). We determined the design trade-offs between the number of patients screened and enrolled when varying the type of patients to enrich and the extent of enrichment needed. For a 2-year overall survival end point in mCRPC state, fully enriching patients with mCRPC having a high-risk score of 3 or more (the 95th percentile of a range of risk scores in patients with mCRPC) was determined to require screening to a maximum of 4,149 patients to enroll 259 patients for the targeted effect size. A nonenriched trial was determined to require enrolling 689 patients to be equivalently powered. We identified a pragmatic alternative, which is to enrich patients with mCRPC with a risk score of 1 or more (the 67th percentile) and an enrichment fraction of 0.25. This would require screening 658 patients to enroll 584 patients, and it maximizes the ability to detect a difference in treatment effect by risk score. A plasma multi-CNA risk score classifier can feasibly be leveraged to design an enrichment trial in mCRPC. Enriching 25% of patients screened with a risk score >1 was observed to be optimal for obtaining an adequately powered, biomarker-based mCRPC-enriched clinical trial.

Increased antibiotic resistance gene abundance linked to intensive bacterial competition in the phyllosphere across an elevational gradient.

Antibiotic resistance genes (ARGs) are ancient and widespread in natural habitats, providing survival advantages for microbiomes under challenging conditions. In mountain ecosystems, phyllosphere bacterial communities face multiple stress conditions, and the elevational gradients of mountains represent crucial environmental gradients for studying biodiversity distribution patterns. However, the distribution patterns of ARGs in the phyllosphere along elevational gradients, and their correlation with bacterial community structures, remain poorly understood. Here, we applied metagenomic analyses to investigate the abundance and diversity of ARGs in 88 phyllosphere samples collected from Mount Tianmu, a national natural reserve. Our results showed that the abundance of ARGs in the phyllosphere increased along elevational gradients and was dominated by multidrug resistance and efflux pumps. The composition of bacterial communities, rather than plant traits or abiotic factors, significantly affected ARG abundance. Moreover, increased ARG abundance was correlated with greater phylogenetic overdispersion and a greater proportion of negative associations in the bacterial co-occurrence networks, suggesting that bacterial competition primarily shapes phyllosphere resistomes. These findings constitute a major advance in the biodiversity of phyllosphere resistomes along elevations, emphasizing the significant impact of bacterial community structure and assembly on ARG distribution, and are essential for understanding the emergence of ARGs.

The Current Role of Metastasis-Directed Therapy for Oligometastatic Renal Cell Carcinoma

Approximately 20% of newly diagnosed renal cell carcinoma (RCC) cases exhibit synchronous metastases, while 20% to 40% of initially localized RCC cases subsequently develop distant metastases after surgical intervention. In the management of oligometastatic RCC with a restricted number of metastatic sites, metastasis-directed therapy (MDT) plays a crucial role within the multimodal therapeutic framework. MDT, which encompasses surgical metastasectomy and stereotactic body radiation therapy (SBRT), seeks to prolong survival and increase quality of life by offering an interruption of systemic therapy. Research has demonstrated that complete metastasectomy is essential for attaining an optimal survival advantage. The criteria for patient selection remain ambiguous; nonetheless, it is crucial to consider the location of metastases and patient risk stratification. SBRT is demonstrably successful in RCC and is being progressively utilized in oligometastatic RCC. The sequencing of advanced systemic agents with comprehensive local treatment of primary and metastatic sites for oligometastatic RCC has demonstrated potential.

The role of morphological adaptability in Vibrio cholerae's motility.

This study highlights the enhanced motility of filamentous Vibrio cholerae in viscous environments, an adaptation that may provide a survival advantage in the human gastrointestinal tract. By demonstrating increased reversal behavior at mucin interfaces, filamentous V. cholerae cells exhibit a superior ability to penetrate the mucus layer, which is crucial for effective colonization and infection. Filamentous cells in bile-supplemented media further underscores their potential role in disease pathogenesis. These findings offer critical insights into the morphological flexibility of V. cholerae and its potential implications for infection dynamics, paving the way for more effective strategies in managing and preventing cholera outbreaks.

Whether monitored anesthesia care is the optimal anesthetic strategy for transcatheter aortic valve implantation surgery? a meta-analysis and systematic review

ObjectivesTo explore whether monitored anesthesia care is more beneficial to the outcome of transcatheter aortic valve implantation.MethodsThe research methodology involved comprehensive searches across major databases, including the Cochrane Library, PubMed, Scopus, and Web of Science, covering the period from January 1, 2010, to March 1, 2024. The aim was to identify trials comparing different anesthetic methods for transcatheter aortic valve implantation. The primary outcomes assessed were mortality and length of hospital stay, while secondary outcomes included common complications such as bleeding, stroke, paravalvular leakage, renal failure, and others. Data synthesis was conducted using risk ratios or standardized mean differences, along with 95% confidence intervals. The study protocol was prospectively registered with PROSPERO (CRD42024507749).ResultsA total of 35 trials and 45,616 patients were included in this study. The results showed that monitored anesthesia care significantly reduced the patient's risk of death, shortened the patient's length of hospital stay, and also reduced the risk of common complications such as paravalvular leakage (RR, 0.80; 95% CI: 0.72 to 0.88; p < 0.00001; I2 = 0) and stroke (RR, 0.80; 95% CI: 0.65 to 0.99; p = 0.04; I2 = 0).ConclusionMonitored anesthesia care has an absolute advantage in patient survival and effectively shortens the length of hospitalization. In addition, it also reduces the risk of complications such as paravalvular leakage and stroke. Monitoring care under anesthesia plays a vital role during TAVI surgery, not only helping to ensure the smooth progress of the surgery and patient safety, but also promoting the patient's recovery and recovery.

Nationwide mortality following acute type B aortic dissection and the survival advantage of obesity among dialysis patients in Japan.

The incidence of acute type B aortic dissection is higher than that of acute type A aortic dissection among patientson dialysis. However, the impact of beingonchronic dialysis on outcomes after type B aortic dissection remains unknown. This study aimed to investigate the trends in in-hospital mortality after type B aortic dissection and the association between body mass index (BMI) and survival paradox on dialysis. This study included 48,889 type B aortic dissection hospitalizations in Japan from 2010 to 2020 based on data from a nationwide administrative database. Logistic regression was used to examine mortality risks and restricted cubic spline to investigate the non-linear association between mortality and BMI. There were 2,116 in-hospital deaths, and the mortality rates were 8.0% in patients receiving chronic dialysis and 4.3% in patients not receiving dialysis. Patients not receiving dialysis had decreased trends of absolute mortality. Meanwhile, patients receiving chronic dialysis had a higher mortality rate from 2010 to 2020. The mortality risk was high in patients receiving chronic dialysis who were underweight and had normal BMI, but not in those who were overweight. Restricted cubic spline analysisshowed that a higher BMI was associated with a lower mortality risk in dialysis patients. This finding contrasted the U-shape observed in patients not receiving dialysis. A lower BMI was associated with a higher risk of in-hospital mortality after type B aortic dissection among dialysis patients, thereby illustrating the obesity paradox. Our findings provide insights that can enhance the management strategies for dialysis patients facing type B aortic dissection.

Sex differences in myocardial infarction care and outcomes: a longitudinal Scottish National Data-Linkage Study.

We investigate sex disparities in management and outcomes of myocardial infarction (MI) in contemporary practice in Scotland. This was a longitudinal cohort study including all MI admissions aged 45-80 years across Scotland between 2010-2016 and 2:1 age, sex, and general practice-matched general population controls. Participants were followed up until the end of 2021. We analysed in-hospital outcomes (percutaneous coronary intervention, secondary prevention and mortality) using Poisson regressions, adjusting for age, comorbidities, and ST-elevation. We used Royston-Parmar models for long-term outcomes (all-cause and cardiovascular mortality, incident cardiovascular events), adjusting for age, comorbidities, and secondary prevention. Of a total 47 063 MI patients, 15 776 (33.5%) were women. Median (inter-quartile range) age was 66 (57, 73) years. Compared to men, women were older and more comorbid, but were less likely to undergo percutaneous coronary intervention [risk ratio (95% confidence interval) - 0.87 (0.86 - 0.89)] or receive secondary prevention at discharge [0.94 (0.93-0.95)]. No in-hospital mortality difference was observed between sexes [1.06 (0.99-1.13) after adjustment]. Over a median follow-up of 8.2 (6.7, 10.1) years, women had higher crude rates of adverse outcomes. After full adjustment, this translated into a lower risk for women compared to men of all-cause mortality [hazard ratio, 0.92 (0.89-0.95)], cardiovascular mortality [0.82 (0.78-0.87)], and cardiovascular events [0.92 (0.88-0.95)]. The female survival advantage seen in general population controls was attenuated in MI patients. Women were undertreated compared to men after MI. Their survival and outcome benefits may be improved further. Poor outcomes in men despite better receipt of secondary prevention require further attention.

Stayin' Alive: Targeting chromatin regulators of clonal hematopoiesis promotes CD8 T cell stemness.

T cell exhaustion remains a significant barrier to immunotherapeutic success for many patients with solid tumors. Growing evidence suggests that enhanced survival and self-renewal properties of a stem-like precursor T cell population (Tpex) is correlated with a survival advantage in immunotherapy. In a recent study published in Science, Kang and colleagues find three epigenetic regulators commonly mutated in clonal hematopoiesis also control Tpex progression to exhaustion. By leveraging the finding that patients with enhanced survival in myelodysplastic syndrome (MDS) had T cell mutations in the ASXL1 gene, this study demonstrates that loss of ASXL1 in T cells preserves their stem-cell like properties of self-renewal and survival leading to increased anti-tumor responses when combined with immunotherapy in both mouse models and human cancers. These findings have significant implications for new therapeutic options that target epigenetic modifiers promoting exhaustion together with immune checkpoint blockade to improve response rates in patients.

In pursuit of a functional cure for follicular lymphoma.

We are now a quarter of a century after the transformative impact of rituximab in improving overall survival for patients with follicular lymphoma. With a burgeoning array of effective immunochemotherapy approaches, we can now frame many patients' expectations of longevity and a "functional cure," with survival estimates for many newly diagnosed patients comparable to age- and gender-matched populations. We highlight not just heterogeneity in disease but also in patients, which influences therapeutic decision-making in an immunochemotherapy era where progression-free survival advances are associated with efficacy-toxicity trade-offs, and no clear overall survival advantage is associated with any specific regimen. We provide the metrics that assist, prognostication both at diagnosis and after initial therapy, but we also highlight the limited long-term follow-up in institutional, population, and clinical trial data sets to inform our survival estimates. Nonetheless, the data are sufficient to empower us to reframe more optimistic conversations with our patients and the lymphoma community, discussions that engender hope and planning for a life lived long, and well, after therapy for follicular lymphoma.