Adverse Clinical Outcomes Research Articles

Clinical significance of preoperative nutritional status in elderly gastric cancer patients undergoing radical gastrectomy: A single-center retrospective study.

The population of elderly patients with gastric cancer is increasing, which is a major public health issue in China. Malnutrition is one of the greatest risk factors for adverse clinical outcomes in elderly patients with gastric cancer. To investigate the preoperative nutritional status and its association with delayed discharge of elderly gastric cancer patients following radical gastrectomy. A total of 783 patients aged 65 years and older harboring gastric adenocarcinoma and following radical gastrectomy were retrospectively analyzed from the prospectively collected database of Zhongshan Hospital of Fudan University between January 2018 and May 2020. The overall rate of malnutrition was 31.8%. The incidence of postoperative complications was significantly higher in the malnourished group compared to the well-nourished group (P < 0.001). Nutritional characteristics in the malnourished group, including body mass index, prognostic nutritional index (PNI), albumin, prealbumin, and hemoglobin, were all significantly lower than those in the well-nourished group. The percentage of patients who received postoperative total nutrient admixture was lower in the malnourished group compared to the well-nourished group (22.1% vs 33.5%, P = 0.001). Age ≥ 70 years (HR = 1.216, 95%CI: 1.048-1.411), PNI < 44.5 (HR = 1.792, 95%CI: 1.058-3.032), operation time ≥ 160 minutes (HR = 1.431, 95%CI: 1.237-1.656), and postoperative complications grade III or higher (HR = 2.191, 95%CI: 1.604-2.991) were all recognized as independent risk factors associated with delayed discharge. Malnutrition is relatively common in elderly patients undergoing gastrectomy. Low PNI is an independent risk factor associated with delay discharge. More strategies are needed to improve the clinical outcome of these patients.

Prospective multicenter study to describe the prevalence, outcomes, and management of phosphate disorders in intensive care patients: Study protocol for part B of the international GUTPHOS study

BackgroundAberrations in blood phosphate (Pi) levels, whether presenting as hypo- or hyperphosphatemia, appear to be associated with clinical complications and adverse outcomes in patients admitted to an intensive care unit (ICU). However, the prevalence of Pi disorders and the association with subsequent factors and organ failures leading to death in ICU patients are poorly described. Despite endeavors to understand the etiology and treatment of low Pi levels from systematic reviews and meta-analyses, the literature lacks comprehensive guidance for managing hypophosphatemia. Hyperphosphatemia, on the other hand, appears to be associated with higher mortality among critically ill patients, yet its prevalence among ICU patients, particularly following phosphate repletion, remains unknown. The present study aims to investigate the prevalence of Pi abnormalities upon ICU admission and their incidence during the first week of ICU stay, the factors associated with Pi alterations, and the effect of phosphate repletion on the normalization of Pi levels, and its associations with clinical outcomes. MethodsThis multicentre, prospective, non-interventional cohort study will include at least 1000 consecutive adult ICU patients (≥18 years) as part B of the GUTPHOS study. Sites are eligible if an anticipated minimal inclusion of 50 eligible patients during eight weeks from January 2024 until June 2024 and daily phosphate measurements during the first seven days of ICU stay are expected. All consecutive adult patients admitted to a participating ICU during the recruitment period, lasting up to eight weeks, or up to 120 patients if enrollment reaches that limit earlier, will be included. Study parameters include study site characteristics, patient demographics, daily assessment of Pi levels, Pi-related treatment, feeding details, renal replacement therapy details, the incidence of refeeding-associated hypophosphatemia and administered medication (during the first seven calendar days of ICU stay). There will be a follow-up period of a maximum of 90 days to document 28- and 90-day all-cause mortality as the primary outcome. Multiple logistic regression will be used to assess independent associations with mortality in addition to Receiver Operating Characteristics curves to identify cut-off Pi values associated with mortality and overcorrection. Linear mixed models will be conducted to assess Pi treatment effects. Subgroup analyses will be performed based on Pi abnormalities observed during ICU admission, categorized as normo-, hypo-, hyper-, or mixed, along with its severity (mild, moderate, or severe). DiscussionThe GUTPHOS study will be the first multicentre, prospective observational cohort study to investigate the prevalence, management practices, and consequent outcomes associated with Pi abnormalities during the first week of ICU admission. Its results may bridge the current evidence gap in repletion protocols while establishing the groundwork for a subsequent randomized controlled trial. Clinical trial registryNCT05909722.

The m6A methyltransferase METTL14 promotes cell proliferation via SETBP1-mediated activation of PI3K-AKT signaling pathway in myelodysplastic neoplasms

N6-methyladenosine (m6A) is the most prevalent epitranscriptomic modification in mammalian mRNA. Recent studies have revealed m6A is involved in the pathogenesis of various malignant tumors including hematologic neoplasms. Nevertheless, the specific roles of m6A modification and m6A regulators in myelodysplastic neoplasms (MDS) remain poorly understood. Herein, we demonstrated that m6A level and the expression of m6A methyltransferase METTL14 were elevated in MDS patients with bone marrow blasts ≥5%. Additionally, m6A level and METTL14 expression were upregulated as the disease risk increased and significantly associated with adverse clinical outcomes. Knockdown of METTL14 inhibited cell proliferation and colony formation ability of MDS cells. Moreover, in vivo experiments showed METTL14 knockdown remarkably reduced tumor burden and prolonged the survival of mice. Mechanistically, METTL14 facilitated the m6A modification of SETBP1 mRNA by formation of METTL3-METTL14 complex, leading to increased stabilization of SETBP1 mRNA and subsequent activation of the PI3K-AKT signaling pathway. Overall, this study elucidated the involvement of the METTL14/m6A/SETBP1/PI3K-AKT signaling axis in MDS, highlighting the therapeutic potential of targeting METTL3-METTL14 complex-mediated m6A modification for MDS therapy.

Rheumatoid arthritis, cardiometabolic comorbidities, and related conditions: need to take action.

Rheumatoid Arthritis (RA) is associated with an increased risk of cardiovascular disease and mortality, however, traditional cardiovascular risk factors do not fully explain this relationship. This high risk of cardiovascular morbidity and mortality in RA has been increasingly acknowledged in past decades, with accumulating evidence that RA is an independent cardiovascular risk factor; RA is also associated with metabolic syndrome, which correlates with disease activity, contributing to the increased prevalence of coronary heart disease in RA patients. Moreover, multimorbidity, including the presence of long-term conditions, impacts adverse clinical outcomes in RA patients, emphasizing the need for holistic management that requires an understanding of shared pathophysiological mechanisms, such as systemic inflammation and immune dysregulation. For all these reasons, the management of RA patients with cardiometabolic comorbidities is a complex endeavor that requires a patient-centered, multidisciplinary approach. In this sense, there is a need to re-evaluate the approach toward a proactive model of care, moving away from a reactive medical paradigm to a multidimensional integrated management model, including aggressive screening, preventive strategies, and tailored therapeutic interventions. The aim of this review was to thoroughly review the literature on cardiometabolic comorbidities and related conditions linked to RA to enable us to identify the necessary actions required to effectively tackle the increasing burden of illness from a fully comprehensive perspective.

Comprehensive Review: Diagnosis, Classification, and Risk Factors of Peritoneal Dialysis-Associated Peritonitis

Peritoneal dialysis (PD) is a predominant modality of renal replacement therapy (RRT) for individuals suffering from end-stage renal disease (ESRD). Peritoneal dialysis-associated peritonitis (PDAP) represents a frequent complication among patients undergoing PD, significantly contributing to adverse clinical outcomes. This review comprehensively examines the diagnosis, classification, and risk factors associated with PDAP, aiming to offer clinical practitioners essential guidance and a foundational framework for effective clinical management.

Determinants of transthyretin levels and their association with adverse clinical outcomes among UK Biobank participants

Transthyretin is a transport protein whose misfolding has been implicated in the development of cardiac amyloidosis. Here, we examine the clinical correlates of transthyretin levels, the differences in transthyretin levels according to the pathogenic V142I TTR variant carrier status, and the association of transthyretin levels with outcomes among 35,206 UK Biobank participants who underwent plasma profiling and were free from prevalent cardiovascular disease and chronic renal disease. Transthyretin levels are lower in females, decrease with increasing C-reactive protein levels, and increase with body mass index, systolic blood pressure, diastolic blood pressure, total cholesterol, albumin levels, triglyceride levels, and creatinine levels. V142I non-carriers [n = 35,167, mean: −0.1 (0.3)] have higher adjusted transthyretin levels compared with the carriers [n = 39, mean: −0.5 (0.3)] (p:<0.001). A standard deviation decrease in transthyretin levels increases the risk of heart failure [HRadj: 1.17 (95% Confidence Interval = 1.08–1.26)] and all-cause mortality [HRadj: 1.18 (95% Confidence Interval = 1.14–1.24)]. This study shows that individuals with low transthyretin levels, such as those carrying the V142I variant, are at a higher risk of heart failure and mortality.

Persistent cool extremities as an independent predictor of adverse clinical outcomes among critically ill patients: a single-center retrospective observational study

Cool extremities representing impaired skin perfusion are a classical sign of shock. We evaluated associations between the presence and persistence of subjective cool extremities observed by caring nurses and clinical outcomes. We conducted a retrospective observational study in an Intensive Care Unit (ICU) at a university hospital in Japan. Patients were divided into two groups based on the presence or absence of subjective cool extremities during the first 24 hours of their ICU stay. We compared their characteristics and outcomes. In total, 2956 patients were analyzed. Patients with cool extremities were older, had higher severity Acute Physiology and Chronic Health Evaluation (APACHE III) scores, had higher in-hospital mortality (4.1% vs 18%, p&lt;0.001), and had a higher prevalence of acute kidney injury requiring renal replacement therapy (2.1% vs 10%, p&lt;0.001) as compared to patients without nurse-reported cool extremities. Multivariable logistic regression showed cool extremities persisting for ≥12 hours were significantly associated with in-hospital death (adjusted Odds Ratio, OR, 1.64) and acute kidney injury requiring renal replacement therapy (adjusted OR 1.82). Patients with subjective cool extremities were more severely ill and had poorer outcomes. Subjective skin temperature assessment may be useful to detect high-risk patients.

Sodium-Glucose Cotransporter-2 Inhibitors Use in Patients with Reduced Kidney Function Hospitalized for Fluid Overload and Heart Failure: An Observational Study.

Sodium-glucose cotransporter-2 inhibitors (SGLT2is) are recommended in kidney disease and heart failure to reduce adverse clinical outcomes, but utilization can vary. To understand potential gaps in clinical practice and identify opportunities for improvement, we aimed to describe the prevalence and factors associated with SGLT2i prescription in patients with reduced kidney function hospitalized for fluid overload and/or heart failure. Single-center observational study of patients with reduced kidney function (eGFR 20-59 mL/min/1.73 m2) hospitalized for fluid overload or heart failure between January 2022 and December 2023. Data were retrieved from electronic medical records. The outcome was SGLT2i prescription at discharge. Potential variables affecting SGLT2i prescription were identified during stakeholder engagement and evaluated using multivariable logistic regression. Among 2,543 patients, the median age was 79 (71, 86) years and admission eGFR was 38.7 (28.4, 49.4) mL/min/1.73 m2. SGLT2i was prescribed to 630 (24.8%) patients at discharge. SGLT2i prescription at discharge was independently associated with cardiovascular disease (OR 1.76, 95% CI: 1.31-2.35), diabetes (OR 1.59, 95% CI: 1.19-2.14), fluid overload or heart failure as the primary discharge diagnosis (OR 1.71, 95% CI: 1.29-2.28), SGLT2i pre-hospitalization (OR 104.91, 95% CI: 63.22-174.08), RAS blocker (OR 2.1, 95% CI: 1.65-2.89), and higher eGFR (OR 1.01, 95% CI: 1.003-1.02) at discharge; but inversely associated with older age (OR 0.97, 95% CI: 0.96-0.98). SGLT2i prescription at discharge was suboptimal among patients with reduced kidney function hospitalized for fluid overload and/or heart failure, especially in older age and more severe kidney disease. Additionally, cardiovascular disease, diabetes, primary discharge diagnosis of fluid overload or heart failure, prior SGLT2i use, and concurrent RAS blocker at discharge were independently associated with SGLT2i prescription at discharge. Interventions are needed to increase clinicians' knowledge and overcome clinical inertia to increase SGLT2i use in patients with fluid overload and heart failure.

Histopathologic degenerative score as a predictor of minimal clinically important difference in pain and functionality following surgical treatment for disc herniation.

Lumbar disc herniation (LDH) often results in significant pain and disability, and histopathologic evaluation of intervertebral discs offers critical insights into treatment outcomes. This prospective observational study explores histopathologic (HP) changes in intervertebral discs (IVD) and their association with clinical outcomes following surgical treatment for lumbar disc herniation (LDH). A cohort of 141 patients undergoing magnetic resonance imaging (MRI)-confirmed LDH surgery underwent HP evaluation using a semi-quantitative Histopathologic Degeneration Score (HDS). Preoperatively and at a six-month follow-up, comprehensive clinical assessment included the Oswestry Disability Index (ODI) and Visual Analog Scale (VAS), with a minimal clinically important difference (MCID) calculated from ODI and VAS. Results indicated significant associations between higher HDS and adverse clinical outcomes, including persistent pain and greater disability post-surgery. Specifically, HDS ≥ 7 was predictive (OR = 6.25, 95%CI: 2.56-15.23) of disability outcomes measured with MCID-ODI (AUC: 0.692, 95%CI: 0.609-0.767, P < 0.001), and HDS ≥ 8 was predictive (OR = 1.72, 95%CI: 1.04-2.77) of persistent pain measured with MCID-VAS (AUC: 0.628, 95%CI: 0.598-0.737, P = 0.008), highlighting the diagnostic potential of HDS in assessing postoperative recovery. This study underscores the potential of HP evaluation using HDS to provide valuable insights into disease progression and outcomes in LDH patients, complementing conventional radiologic methods. The findings support the application of personalized treatment strategies based on HP findings while acknowledging challenges in interpretation and clinical implementation.

Impact of non-alcoholic fatty liver disease and fibrosis on mortality and kidney outcomes in patients with type 2 diabetes and chronic kidney disease: A multi-cohort longitudinal study.

To evaluate the impact of non-alcoholic fatty liver disease (NAFLD) presence and fibrosis risk on adverse outcomes in patients with type 2 diabetes and chronic kidney disease. Data were sourced from two longitudinal cohorts: 1172 patients from the National Health and Nutrition Examination Survey (NHANES) and 326 patients from the kidney biopsy cohort at the West China Hospital of Sichuan University. Cox regression estimated hazard ratios (HRs) for NAFLD and liver fibrosis concerning adverse clinical outcomes. Subsequently, a two-sample Mendelian randomization study using genome-wide association study statistics explored NAFLD's potential causal link to cardio-cerebrovascular events. In the NHANES cohort, NAFLD stood as an independent risk factor for various outcomes: overall mortality [HR 1.53 (95% confidence interval, CI 1.21-1.95)], mortality because of cardio-cerebrovascular diseases [HR 1.63 (95% CI 1.12-2.37)], heart disease [HR 1.58 (95% CI 1.00-2.49)], and cerebrovascular disease [HR 3.95 (95% CI 1.48-10.55)]. Notably, advanced liver fibrosis, identified by a fibrosis-4 (FIB-4) score >2.67, exhibited associations with overall mortality, cardio-cerebrovascular disease mortality and heart disease mortality. Within the kidney biopsy cohort, NAFLD correlated with future end-stage kidney disease [ESKD; HR 2.17 (95% CI 1.41-3.34)], while elevated FIB-4 or NAFLD Fibrosis Scores predicted future ESKD, following full adjustment. Liver fibrosis was positively correlated with renal interstitial fibrosis and tubular atrophy in biopsies. Further Mendelian randomization analysis supported a causal relationship between NAFLD and cardio-cerebrovascular events. In patients with type 2 diabetes and chronic kidney disease, the NAFLD presence and elevated FIB-4 scores link to heightened mortality risk and ESKD susceptibility. Moreover, NAFLD shows a causal relationship with cardio-cerebrovascular events.

Associations between dietary potassium intake and urinary potassium excretion: a protocol for systematic review and meta-analysis

BackgroundWhile numerous studies have reported associations between low dietary potassium intake and adverse clinical outcomes, methods to estimate potassium intake, mainly self-reported dietary measures and urinary potassium excretion, entail certain limitations. Self-reported measures are subject to underreporting and overreporting. Urinary potassium excretion is affected by multiple factors including renal function. Revealing the degree of bias inherent in these measures would help accurately assess potassium intake and its association with disease risk. We aim to summarize evidence on the strength of the associations between potassium intake estimated from 24-h urinary potassium excretion and potassium intake estimated from self-reported dietary measures or objective quantification methods in populations with different kidney function levels and age groups. We also aim to identify factors that affect the association strength.MethodsWe will search for potentially eligible studies that examined associations between self-reported potassium intake, 24-h urinary potassium excretion, and objectively quantified potassium intake, using MEDLINE (PubMed), Embase, Web of Science, and Scopus. Studies on children, adolescents, adults, and the elderly are eligible. Studies of patients on dialysis will be excluded. Collective study results, including a meta-analysis, will be synthesized if an adequate number of studies examining similar dietary potassium intake estimation methods are found. Analyses will be performed separately according to age groups and renal function. For the meta-analysis, fixed-effects or random-effect models will be employed depending on the degree of study heterogeneity to combine across studies the correlation coefficient, ratio, or standardized mean difference for potassium intake, comparing dietary potassium intake based on self-reported or objectively quantified methods and intake based on 24-h urinary potassium excretion. The degree of heterogeneity among included studies will be examined by calculating I2 statistics. To investigate sources of study heterogeneity, random-effects meta-regression analyses will be performed.DiscussionRevealing the strength of the association between dietary and urinary measures in populations with different levels of kidney function and age groups will enhance researchers’ and clinicians’ ability to interpret studies that utilize these measures and help establish a more solid evidence base for the role of potassium intake in changing chronic disease risk. Identifying factors that modify the associations between these measures may aid in developing predictive models to estimate actual potassium intake.Systematic review registrationPROSPERO CRD42022357847.

Population-wide eGFR percentiles in younger adults and clinical outcomes.

Identifying meaningful estimated glomerular filtration rate (eGFR) reductions in younger adults (<65 years) could guide prevention efforts. To aid in interpretation and identification of young adults at risk, we examined the association of population-level eGFR percentiles relative to the median by age and clinical outcomes. We conducted a retrospective cohort study of 8.7 million adults from Ontario, Canada from age 18 to 65 from 2008 to 2021 with an eGFR measure (both single outpatient value and repeat measures). We calculated median eGFR values by age and examined the association of reduced eGFR percentiles (≤10th, 5th, 2.5th and 1st) with outcomes using time to event models. Outcomes were a composite of all-cause mortality, major adverse cardiac outcomes (MACE) with/without heart failure (MACE+) and kidney failure as well as each component individually. From age 18 to 65, the median eGFR declined with age (range 128 to 90) and across percentiles [eGFR ranges 102 to 68 for ≤10th, 96 to 63 for ≤5th, 90 to 58 for ≤2.5th and 83 to 54 for 1st]. The adjusted rate for any adverse outcome was elevated at ≤ 10th percentile (HR 1.14 95%CI 1.10-1.18) and was consistent for all-cause mortality, MACE, MACE+ and predominant for kidney failure (HR 5.57 95%CI 3.79-8.19) compared to the median eGFR for age. Young adults with an eGFR in the lower percentiles were less likely to be referred to a specialist, have a repeat eGFR or albumin to creatinine ratio measure. eGFR values at the 10th percentile or lower based on a population-level distribution are associated with adverse clinical outcomes and in younger adults (18 to 39) this corresponds to a higher level of eGFR that may be underrecognized. Application of population-based eGFR percentiles may aid interpretation and improve identification of younger adults at risk.

Surgeon Skill and Perioperative Outcomes in Robot-Assisted Partial Nephrectomy

Technical skill in complex surgical procedures may affect clinical outcomes, and there is growing interest in understanding the clinical implications of surgeon proficiency levels. To determine whether surgeon scores representing technical skills of robot-assisted kidney surgery are associated with patient outcomes. This quality improvement study included 10 urological surgeons participating in a surgical collaborative in Michigan from July 2021 to September 2022. Each surgeon submitted up to 7 videos of themselves performing robot-assisted partial nephrectomy. Videos were segmented into 6 key steps, yielding 127 video clips for analysis. Each video clip was deidentified and distributed to at least 3 of the 24 blinded peer surgeons from the collaborative who also perform robot-assisted partial nephrectomy. Reviewers rated technical skill and provided written feedback. Statistical analysis was performed from May 2023 to January 2024. Reviewers scored each video clip using a validated instrument to assess technical skill for partial nephrectomy on a scale of 1 to 5 (higher scores indicating greater skill). For all submitting surgeons, outcomes from a clinical registry were assessed for length of stay (LOS) greater than 3 days, estimated blood loss (EBL) greater than 500 mL, warm ischemia time (WIT) greater than 30 minutes, positive surgical margin (PSM), 30-day emergency department (ED) visits, and 30-day readmission. Among the 27 unique surgeons who participated in this study as reviewers and/or individuals performing the procedures, 3 (11%) were female, and the median age was 47 (IQR, 39-52) years. Risk-adjusted outcomes were associated with scores representing surgeon skills. The overall performance score ranged from 3.5 to 4.7 points with a mean (SD) of 4.1 (0.4) points. Greater skill was correlated with significantly lower rates of LOS greater than 3 days (-6.8% [95% CI, -8.3% to -5.2%]), EBL greater than 500 mL (-2.6% [95% CI, -3.0% to -2.1%]), PSM (-8.2% [95% CI, -9.2% to -7.2%]), ED visits (-3.9% [95% CI, -5.0% to -2.8%]), and readmissions (-5.7% [95% CI, -6.9% to -4.6%]) (P < .001 for all). Higher overall score was also associated with higher partial nephrectomy volume (β coefficient, 11.4 [95% CI, 10.0-12.7]; P < .001). In this quality improvement study on video-based evaluation of robot-assisted partial nephrectomy, higher technical skill was associated with lower rates of adverse clinical outcomes. These findings suggest that video-based evaluation plays a role in assessing surgical skill and can be used in quality improvement initiatives to improve patient care.

Atrial fibrillation fact sheet in Korea 2024 (part 1): epidemiology of atrial fibrillation in Korea

Background and objectivesThis study aimed to analyze and present updated trends in atrial fibrillation (AF) epidemiology within the Korean population, providing a foundation for planning and implementing appropriate management and treatment strategies for patients with AF.Patients and methodsWe used the Korean National Health Insurance Service database to evaluate the prevalence, incidence, comorbidities, and clinical adverse outcomes of patients with AF in Korea between 2013 and 2022.ResultsAF prevalence in Korean adults aged ≥ 20 years doubled (1.1 to 2.2%) between 2013 and 2022, with significant increases observed across various sex and age groups. Similarly, the number of newly diagnosed patients with AF per year increased steadily, with the incidence rising from 184 to 275 per 100,000 person-years, particularly among older populations. Over this period, the mean age of patients with AF increased from 67.7 to 70.3 years, and comorbidities prevalence and CHA2DS2-VASc score rose significantly, indicating a higher stroke risk. Compared with patients without AF, AF was associated with an increased risk of mortality (hazard ratio [HR]: 1.78), ischemic stroke (HR: 2.39), major bleeding (HR: 2.10), myocardial infarction (HR: 1.44), and heart failure admission (HR: 2.42).ConclusionAF prevalence and incidence have steadily increased between 2013 and 2022, with a more pronounced increase in older patients. Patients with AF are increasingly becoming a high-risk population and are at increased risk of clinical adverse outcomes compared to non-AF patients. Therefore, a sustained national effort to improve AF awareness and comprehensive care quality for patients with AF is required.

Rational Pharmacotherapy in Type 2 Diabetes: Danish Data From 2002 to 2020 on Mortality, Diabetes- Related Outcomes, Adverse Events, and Medication Expenses.

Developments in pharmacotherapy and management of type 2 diabetes may have shifted the balance of treatment benefits versus harms and costs over the past decades. This study aimed to describe the trends in this balance. We followed the Danish population with type 2 diabetes between 2002 and 2020, analyzing their medication use in relation to treatment benefits (such as mortality and diabetes-related outcomes), adverse events, and medication costs. Using multivariate analyses, we adjusted for potential confounders, including age, sex, and socioeconomic status. The study included 461,805 individuals. From 2002 to 2020, the median age increased from 66 to 68 years, and the mean number of comorbidities increased from 5.2 to 8.8. The overall incidence of cardiovascular, renal, and other important adverse clinical outcomes decreased. Similarly, the rate of some adverse events, such as gastric bleeding, hypoglycemia, and falls declined, whereas the incidence of electrolyte imbalances and ketoacidosis increased. The average per-patient cost was reduced by 8%, but total medication expenses increased by 148% due to an expanding population size, lowered costs of most cardiovascular medications, and increasing costs for glucose-lowering drugs. Advancements in type 2 diabetes management have led to reduced risk of both diabetes-related outcomes and treatment harms, while maintaining relatively stable per-patient medication expenses. Although these trends are multifactorial, they suggest more rational pharmacotherapy. Still, increased risk of certain adverse events, along with increasing costs for glucose-lowering medications, underscores the need for ongoing vigilance and risk-benefit analysis.

Risk of type 2 diabetes, MASLD and cardiovascular disease in people living with polycystic ovary syndrome.

Abstract Background Polycystic ovary syndrome (PCOS) is associated with adverse clinical outcomes that may differ according to PCOS phenotype. Methods Using UK Biobank data, we compared the incidence of type 2 diabetes (T2D), metabolic dysfunction associated steatotic liver disease, cardiovascular disease (CVD), hormone-dependent cancers, and dementia between PCOS participants and age- and body mass index-matched controls. We also compared multiorgan (liver, cardiac, and brain) magnetic resonance imaging (MRI) data and examined the impact of PCOS phenotype (hyperandrogenic and normoandrogenic) on these outcomes. Results We included 1008 women with PCOS (defined by diagnostic codes, self-reported diagnoses, or clinical/biochemical features of hyperandrogenism and a/oligoCmenorrhoea) and 5017 matched controls (5:1 ratio); median age, 61 years, body mass index, 28.4 kg/m². Adjusted Cox proportional hazard modeling demonstrated PCOS participants had greater incident T2D [hazard ratio (HR) 1.47; 95% confidence interval (CI), 1.11-1.95] and all-cause CVD (1.76; 1.35-2.30). No between-group differences existed for cancers or dementia. Liver MRI confirmed more PCOS participants had hepatic steatosis (proton density fat fraction &amp;gt;5.5%: 35.9 vs 23.9%; P = .02) and higher fibroinflammation (corrected T1 721.4 vs 701.5 ms; P = &amp;lt;.01) vs controls. No between-group difference existed for cardiac (biventricular/atrial structure and function) or brain (grey and white matter volumes) imaging. Normoandrogenic (but not hyperandrogenic) PCOS participants had greater incident all-cause CVD (1.82; 1.29-2.56) while hyperandrogenic (but not normoandrogenic) PCOS participants were more likely to have hepatic steatosis (8.96 vs 6.04 vs 5.23%; P = .03) with greater fibroinflammation (776.3 vs 707.7 vs 701.9 ms; P=&amp;lt;.01). Conclusion Cardiometabolic disease may be increased in PCOS patients with a disease phenotype-specific pattern.

Early single session of hyperbaric oxygen therapy mitigates renal apoptosis in lipopolysaccharides-induced endotoxemia in rats.

Sepsis-associated acute kidney injury (SA-AKI) is a prominent sepsis complication, often resulting in adverse clinical outcomes. Hyperbaric oxygen therapy (HBOT), known for its anti-inflammatory characteristics, antioxidant effects, and ability to deliver high oxygen tension to hypo-perfused tissues, offers potential benefits for SA-AKI. This study investigated whether HBOT improved renal injury in sepsis and elucidated its underlying mechanisms. A lipopolysaccharide (LPS)-induced endotoxemia model was established using 8-week-old C57BL/6 mice. Thirty minutes post-LPS administration, a group of mice underwent HBOT at a 2.5 atmospheric pressure absolute with 100% oxygen for 60 minutes. After 24 hours, all mice were euthanized for measurements. Our results demonstrated that HBOT effectively mitigated renal tubular cell apoptosis. Additionally, HBOT significantly reduced phosphorylated p53 proteins and cytochrome C levels, suggesting that HBOT may attenuate renal apoptosis by impeding p53 activation and cytochrome C release. Notably, HBOT preserved manganese-dependent levels of superoxide dismutase, an antioxidant enzyme, compared to the LPS group. Furthermore, transforming growth factor beta (TGF-β)/Smad4 and alpha smooth muscle actin expressions were significantly reduced in the LPS + HBOT group. An early single session of HBOT exhibited renoprotective effects in LPS-induced endotoxemia mice models by suppressing p53 activation and cytochrome C levels to mitigate apoptosis. The observed TGF-β decrease, downstream Smad expression reduction, and antioxidant capacity preservation following HBOT may contribute to these effects.

Clinical outcomes of patients with atrial fibrillation in relation to multimorbidity status changes over time and the impact of ABC pathway compliance: a nationwide cohort study.

Patients with atrial fibrillation (AF) commonly have associated comorbidities. The primary aim was to determine the effect of increasing numbers of comorbidity on clinical outcomes. The secondary aims were (1) the association of comorbidities with oral anticoagulants (OAC) discontinuation, and quality control, (2) the impact of holistic care based on the ABC pathway on clinical outcomes. The primary outcome was the composite of all-cause death, ischemic stroke/systemic embolism, major bleeding, and heart failure. A total of 3405 patients were enrolled; mean age 67.8 ± 11.3 years, 41.8% female. Compared to low comorbidity group [n = 897 (26.3%)], hazard ratios (HR) and 95% confidence intervals (CI) for the composite outcome in the high [n = 929 (27.3%)] and moderate comorbidity [n = 1579 (46.4%)] groups were 5.40 (4.20-6.94) and 2.54 (1.97-3.27), respectively. ABC pathway adherence was associated with reduction of the composite outcome overall (HR 0.63; 0.54-0.74). High comorbidity adversely impacted on OAC use, OAC discontinuation, and quality of warfarin control. If quality of anticoagulation control was included as part of the ABC pathway adherence, the reduction in composite outcome risk was greater (HR 0.46; 0.36-0.58). During 3-year follow-up, 33.9% changed from low- to the moderate-high comorbidity groups and 22.3% changed from moderate- to the high comorbidity group. In conclusion, comorbidity burden in AF patients is an important determinant of clinical outcomes, and changed over time. OAC use, OAC discontinuation, and quality of OAC control were impacted by comorbidity burden. ABC pathway adherence was associated with a reduced risk of adverse clinical outcomes.

Effect of low blood pressure on prognosis of acute heart failure

Low blood pressure (BP) is associated with poor outcomes in patients with heart failure (HF). We investigated the influence of initial BP on the prognosis of HF patients at admission, and prescribing patterns of HF medications, such as angiotensin-converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARB), and beta-blockers (BB). Data were sourced from a multicentre cohort of patients admitted for acute HF. Patients were grouped into heart failure reduced ejection fraction (HFrEF) and HF mildly reduced/preserved ejection fraction (HFmrEF/HFpEF) groups. Initial systolic and diastolic BPs were categorized into specific ranges. Among 2778 patients, those with HFrEF were prescribed ACEi, ARB, or BB at discharge, regardless of their initial BP. However, medication use in HFmrEF/HFpEF patients tended to decrease as BP decreased. Lower initial BP in HFrEF patients correlated with an increased incidence of all-cause death and composite clinical events, including HF readmission or all-cause death. However, no significant differences in clinical outcomes were observed in HFmrEF/HFpEF patients according to BP. Initial systolic (< 120 mmHg) and diastolic (< 80 mmHg) BPs were independently associated with a 1.81-fold (odds ratio [OR] 1.81, 95% confidence interval [CI] 1.349–2.417, p < 0.001) and 2.24-fold (OR 2.24, 95% CI 1.645–3.053, p < 0.001) increased risk of long-term mortality in HFrEF patients, respectively. In conclusion, low initial BP in HFrEF patients correlated with adverse clinical outcomes, and BP < 120/80 mmHg independently increased mortality. However, this relationship was not observed in HFmrEF/HFpEF patients.

Impact of a codesigned and coproduced patient-centred discharge form on communication and understanding.

Adverse clinical outcomes and patient dissatisfaction with care often have elements of poor communication. Factors such as illness and pharmacotherapy can affect cognition, and overestimation of patients' health literacy may contribute to suboptimal communication with patients regarding their hospitalisation and post-discharge instructions. Improved patient understanding and recall of their diagnoses and treatment is critical for adherence to treatment, follow-up and optimal clinical outcomes. The aim of the study was to assess whether a coproduced and codesigned patient-centred discharge form (PCDF) improves patients' understanding of their discharge diagnosis, in-hospital treatment and post-discharge plan. A sample of 111 patients was enrolled through simple randomisation by admission to one of two identically operating general medicine wards. Over a 3-month period, 59 patients received the coproduced and codesigned form and 52 patients were controls. Assessment of patients' understanding of diagnosis, in-hospital management, post-discharge instructions and overall experience of care was undertaken by a blinded phone survey conducted approximately 6 days after discharge. Patients who received PCDF were significantly more likely to report adequate understanding of their hospital management (P < 0.001) and the post-discharge plan (P < 0.001). There was no statistically significant difference between the intervention and control groups in terms of understanding of diagnosis. Patients who received PCDF reported better understanding of care and recall of admission. The use of PCDF is associated with improved patient understanding with respect to their hospital management and post-discharge instructions. It is also associated with high levels of satisfaction as assessed by measures of patient experience.