The factors governing the presence and severity of orthostatic hypotension (OH) in multiple system atrophy (MSA) may differ. We investigated factors independently associated with OH and severe OH in MSA, and assessed the consistency of these associations across subtypes.

We examined the clinical data of 242 MSA patients who had blood pressure evaluations to assess OH. We analyzed the clinical data of MSA patients with and without OH, as well as those with mild and severe OH, focusing on clinical characteristics and brain MRI features to identify factors associated with OH presence and severe OH.

OH was present in 136 patients (56.2%). MSA-C subtype (OR = 2.42, 95% CI = 1.33-4.43, p = 0.004), probable MSA (OR = 2.68, 95% CI = 1.49-4.80, p = 0.001), and higher UMSARS-I scores (OR = 1.10, 95% CI = 1.03-1.17, p = 0.005) were independently associated with the presence of OH. Among OH-positive patients, male (OR = 2.57, 95% CI = 1.21-5.44, p = 0.014) and higher NMSS scores (OR = 1.06, 95% CI = 1.02-1.11, p = 0.009) were independently associated with severe OH, whereas MSA subtype was not. Subgroup analyses showed directionally consistent associations for male sex and NMSS across MSA-C and MSA-P subgroups. The association between NMSS and severe OH was statistically significant in the MSA-C subgroup (OR = 1.09, 95% CI = 1.03-1.15, p = 0.004), whereas the remaining subgroup estimates did not reach statistical significance. No neuroimaging marker was associated with OH.

Factors associated with OH presence differed from those associated with severe OH in MSA. MSA-C subtype, diagnostic certainty, and UMSARS-I score were associated with OH presence, whereas male sex and NMSS burden were associated with severe OH.

Early risk stratification is critical for critically ill patients with ischemic stroke. The prognostic value of the lactate-to-albumin ratio (LAR) remains unclear in this population.

This single-center retrospective cohort study enrolled adult ICU patients with ischemic stroke from West China Hospital. LAR was calculated using the first lactate and albumin values on ICU admission. Log-transformed LAR was adopted as the main exposure, and the primary outcome was in-hospital mortality. Multivariable logistic regression, ROC analysis, quartile stratification, subgroup, and sensitivity analyses were performed among 749 patients with complete exposure and outcome data, of whom 576 had complete covariate data and comprised the primary multivariable regression cohort.

A total of 749 patients were included, with an in-hospital mortality rate of 30.7%. In complete-case multivariable analysis (N = 576; deaths = 172), log-transformed LAR was independently associated with in-hospital mortality (OR = 1.44, 95%CI: 1.09-1.91, p = 0.010) after full adjustment. Each two-fold increase in LAR was associated with a 29% increase in mortality odds. The highest LAR quartile had a significantly higher mortality risk than the lowest quartile (OR = 2.16, 95%CI: 1.21-3.92). LAR showed modest predictive ability (AUC = 0.628). When modeled as a raw continuous LAR, the direction of association remained consistent but did not reach conventional statistical significance (OR 1.23; 95% CI 0.97-1.56; p = 0.083). Moreover, no significant interaction or non-linearity was found.

Elevated LAR is independently linked to higher in-hospital mortality among critically ill ischemic stroke patients. It may serve as a simple adjunctive marker for early risk stratification.

Ageing biomarkers quantify molecular, physiological or functional features that vary between individuals as they age and may improve prediction of health outcomes beyond chronological age. Recently, plasma proteomics have been used to estimate the biological ages of 11 human organs. Although accelerated organ ageing is associated with higher mortality risk, systematic benchmarking against established ageing biomarkers is lacking. Here, we pursued two complementary aims. First, we benchmarked proteomic organ clocks against multimodal ageing biomarkers for associations with 16-year all-cause mortality in the Lothian Birth Cohort 1936 (LBC1936) using Cox regression (861 participants; 444 deaths). Biomarkers included the epigenetic clock GrimAge2, telomere length, physical function (grip strength, walk time and respiratory function), neuroimaging and cognitive measures. Among proteomic clocks, accelerated liver (HR_perSD [95% CI] = 1.43 [1.30-1.58]), immune (1.42 [1.29-1.57]) and heart (1.38 [1.25-1.53]) ageing were most strongly associated with increased mortality risk. However, older epigenetic age, smaller total brain and grey matter volumes, reduced respiratory function and poorer cognition showed stronger associations with mortality (HR_perSD = 1.44-1.62). Second, survival analyses of 9703 plasma protein targets identified 368 candidates associated with mortality, with high-risk proteins enriched for immune functions, and low-risk proteins involved in genomic stability and cellular maintenance. GDF15 (HR_perSD [95% CI] = 1.56 [1.42-1.72]), WFDC2 (1.47 [1.33-1.62]) and TIMP1 (1.45 [1.29-1.62]) were the leading proteomic candidates associated with mortality. This study provides a systematic, cross-modal benchmarking of proteomic organ clocks against established ageing biomarkers and identifies proteins and biological functions associated with mortality risk.

Survival with good neurological function after out-of-hospital cardiac arrest (OHCA) remains low. Extracorporeal cardiopulmonary resuscitation (eCPR) may benefit selected patients, but it is unclear how many patients in a mixed urban-rural European region would be eligible, whether regional case volumes justify dedicated eCPR programmes, and whether an in-hospital strategy after intra-arrest transport can meet a 60-minute low-flow target.

We conducted a retrospective cohort study of OHCA cases in the city and county of Göttingen, Germany (January 2015-February 2025). eCPR eligibility was assessed using a local protocol and a stricter modified ELSO definition. Eligibility was first determined at emergency medical services (EMS) arrival and then re-evaluated for three hypothetical intra-arrest transport strategies in which transport was initiated after 10, 15, or 20 minutes of on-scene conventional cardiopulmonary resuscitation (cCPR). Scene-to-hospital travel times were modelled and patients were classified according to whether they would be eligible for eCPR upon hospital arrival. A complementary analysis estimated time from collapse to hypothetical eCPR initiation under an on-scene scenario, split into simultaneous dispatch of a dedicated eCPR team (S1a) and delayed dispatch after 10 minutes of on-scene evaluation by the primary EMS team (S1b), and an in-hospital scenario following intra-arrest transport (S2), incorporating documented timing of sustained return of spontaneous circulation (ROSC).

Of 2,218 OHCA cases, 1,696 registry-documented patients were analysed (median age 71.5 years; 67.5% male; shockable rhythm 20.5%). At EMS arrival, 348 patients (20.5%) met local and 149 (8.8%) modified ELSO criteria. With transport initiated after 10/15/20 minutes of on-scene cCPR, 11.1%/9.8%/8.8% (local) and 3.8%/3.1%/2.8% (modified ELSO) would have been eligible at hospital arrival. Extrapolated regional case volume was approximately 46 (local) and 20 (modified ELSO) eligible patients per year at EMS arrival. In patients who met local eCPR criteria the number of patients with sustained ROSC exceeded those without at 13.4 minutes after EMS arrival. Median estimated time from collapse to eCPR was 37 minutes under S1a (94.8% within 60 minutes) and 54 minutes under S1b (71.6% within 60 minutes) versus 75 minutes under S2 (<1% within 60 minutes). After excluding patients with ROSC before hypothetical eCPR initiation, 47.4% (S1a) and 31.6% (S1b) in the local cohort and 36.9% (S1a) and 24.8% (S1b) in the modified ELSO cohort would both still have required and could have received on-scene eCPR within 60 minutes.

A substantial number of OHCA patients in our region met eCPR eligibility criteria, but hospital arrival did not equate to eCPR initiation. Given realistic procedural time intervals, in-hospital eCPR following intra-arrest transport rarely met the 60-minute target, whereas on-scene eCPR might have remained feasible for most eligible patients.

Primary aldosteronism (PA) is a common but frequently ignored cause of hypertension, particularly in patients with normal serum potassium and aldosterone levels.

We report the case of a 70-year-old Han Chinese man with a 20-year history of hypertension who presented with normokalemia and normal plasma aldosterone levels. Despite this, laboratory evaluation revealed suppressed direct renin concentration (DRC) and a markedly elevated aldosterone-to-renin ratio (ARR), raising suspicion for PA. Adrenal computed tomography demonstrated bilateral nodular adrenal thickening. The patient had persistently uncontrolled blood pressure despite triple antihypertensive therapy with amlodipine besylate, valsartan/hydrochlorothiazide, and bisoprolol. Spironolactone was added to the existing regimen but was subsequently discontinued due to intolerance. Treatment was then switched to finerenone, a nonsteroidal mineralocorticoid receptor antagonist. During follow-up, blood pressure was well controlled, serum potassium levels remained stable, and both plasma renin concentration and the aldosterone-to-renin ratio normalized.

This case highlights the diagnostic challenge of PA evaluation in a patient with normal-range aldosterone and suppressed renin and provides clinical experience with finerenone after intolerance to a steroidal mineralocorticoid receptor antagonist.

To investigate the association between hobby engagement and the risk of hypertension using data from the China Health and Retirement Longitudinal Study (CHARLS) and the Health and Retirement Study (HRS).

This study included 7,112 participants aged ≥ 50 years from CHARLS and 4,937 participants aged ≥ 50 years from HRS. Hobby engagement was assessed at baseline and at follow-up, and longitudinal changes in hobby engagement were analyzed. The primary outcome was incident hypertension. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were also measured. Cox proportional hazards models were used to estimate hazard ratios (HRs) for incident hypertension, and changes in SBP and DBP with hobby engagement were examined using linear mixed-effects models. Kaplan-Meier curves and subgroup analyses were performed.

In baseline analyses, participants with hobby engagement had a significantly lower risk of developing hypertension compared to non-engaged participants in both CHARLS (HR = 0.84, 95% CI: 0.76,0.93) and HRS (HR = 0.86, 95% CI: 0.78,0.96) after full adjustment. In longitudinal analyses of hobby engagement patterns, persistent hobby engagement had the greatest protective effect in both cohorts compared with persistent hobby non-engagement in CHARLS (HR = 0.77, 95% CI: 0.68,0.88) and HRS (HR = 0.83, 95% CI: 0.73,0.95), respectively. Hobby engagement was associated with reductions in SBP (-0.52 mmHg per year) and DBP (-0.24 mmHg per year) over time in CHARLS. However, this effect was not observed in HRS.

Hobby engagement is a significant protective factor against hypertension, with stronger benefits observed among individuals who maintained their hobby engagement over time. These findings support the integration of hobby-based interventions into public health strategies for preventing hypertension in middle-aged and older populations.

Adrenal insufficiency (AI) is a rare but potentially life-threatening cause of perioperative hemodynamic instability characterized by an inadequate cortisol response to physiological stress.

We report a case of a 77-year-old woman undergoing oblique lumbar interbody fusion who developed profound intraoperative hypotension refractory to fluid resuscitation and multiple vasopressors. Notably, she had a history of corticosteroid therapy for rheumatoid arthritis that had been discontinued nearly 3 decades earlier. She also exhibited extreme skin fragility.

AI was clinically suspected based on persistent vasopressor-resistant hypotension, a remote history of corticosteroid therapy, and extreme skin fragility.

Suspecting AI, intravenous hydrocortisone was administered postoperatively, resulting in rapid hemodynamic stabilization and subsequent weaning of vasopressors.

Pre- and postoperative biochemical testing was inconclusive for definitive AI. However, the clinical presentation and dramatic response to steroid administration strongly suggested surgical stress-related AI. The patient was discharged without any complications.

This case underscores the importance of maintaining a high index of suspicion for AI in patients with unexplained, vasopressor-resistant hypotension, even those with a remote history of corticosteroid use, as timely empirical treatment can be life-saving.

Hypertension remains one of the leading modifiable risk factors for cardiovascular disease and premature mortality worldwide. Blood pressure (BP) management is particularly challenging in patients with coexisting type 2 diabetes (T2D), chronic kidney disease (CKD), or heart failure (HF). Sodium-glucose cotransporter 2 (SGLT2) inhibitors have become an integral component of contemporary cardiorenal therapy and have consistently demonstrated additional BP-lowering effects across diverse clinical settings. This narrative review synthesizes the current clinical evidence regarding the antihypertensive effects of dapagliflozin and summarizes the biological mechanisms that may contribute to these effects, including osmotic diuresis and natriuresis, weight reduction, modulation of the sympathetic nervous system, enhanced uric acid excretion, and attenuation of oxidative stress, inflammation, and vascular dysfunction. Across clinical studies, reductions in systolic BP (SBP) generally exceed those in diastolic BP (DBP), although the physiological basis underlying this differential response remains incompletely understood. Dapagliflozin has demonstrated good tolerability and antihypertensive effects in clinical applications, its long-term use may be limited by the risk of genital infections. Collectively, the available evidence supports dapagliflozin as a cardiorenal therapeutic agent that may provide additional BP-lowering benefits in patients with hypertension and concomitant T2D, CKD, or HF, rather than as a substitute for conventional antihypertensive therapy. Future hypertension-focused clinical studies are warranted to further define its role in hypertension management.

Diabetic macular edema (DME) is a common microvascular complication of diabetes and a major cause of vision impairment. Intravitreal vascular endothelial growth factor (VEGF) inhibitors remain the gold standard for its management. However, the high cost and limited accessibility of reference anti-VEGF agents have driven growing interest in biosimilars-biologic therapies designed to match the efficacy, safety, and immunogenicity of their reference products. Following the expiration of patents for agents such as aflibercept and ranibizumab, several biosimilars have been developed, approved, and introduced into clinical practice. Evidence from real-world studies-including RE-ENACT2 (REal-life assessmENt of safety And effeCTiveness of Razumab) and REAR-RD2 (REal-world observational study to evaluate the risk factors in the management of REtinal Diseases-2)-as well as randomized clinical trials such as INSIGHT and CT-P42 has demonstrated clinical equivalence between these biosimilars and their reference anti-VEGF counterparts in the treatment of DME. This article provides an updated overview of the current evidence base, recent advances in regulatory pathways, and ongoing challenges in integrating biosimilars into routine DME management.

Type 2 long QT syndrome (LQT2) increases the risk of cardiac arrest and sudden death due to reduced rapid delayed rectifier potassium currents (IKr) in the heart. Caused by loss-of-function genetic variants in the hERG K⁺ channel, LQT2 might benefit from variant-targeted therapy approaches. T1019PfsX38 and Q1070X are LQT2-causing variants reported in Oman and Saudi Arabia. Although nonsense-mediated mRNA decay (NMD) has been proposed to contribute to reduced expression of these truncating variants, it remains unclear whether residual mutant hERG channel function can be pharmacologically enhanced. We used the patch-clamp technique and examined the effects of the hERG potentiator NS1643 on wild-type-, T1019PfsX38- and Q1070X-hERG channels expressed in HEK293 cells. We started by assessing the response of these variants under the influence of a ventricular action potential clamp protocol, then used additional protocols to elucidate the drug's mechanism of action. NS1643 [10 µM] enhanced the repolarization currents in wild-type-, T1019PfsX38- and Q1070X-expressing cells. Its effect was associated with accelerated activation rates and a negative shift in the voltage dependence of activation. In addition, NS1643 suppressed fast deactivation transitions. We conclude that the functions of T1019PfsX38- and Q1070X-hERG channels can be augmented by hERG potentiators if NMD is incomplete, which may facilitate the development of a mechanism-based rescue approach.