Medicine and Pharmacology

Abstract: Background: Circulating α-Klotho is a longevity-related protein with anti-inflammatory and cytoprotective functions. Evidence on its relationship with individual leukocyte populations is limited, while eosinophils may have both inflammatory and tissue-homeostatic roles. We examined the association of serum α-Klotho with absolute and relative eosinophil measures in older adults. Methods: This cross-sectional analysis included 502 community-dwelling adults aged ≥60 years with serum α-Klotho data; 493 also had a complete blood count with differential. α-Klotho was analyzed continuously because no universally accepted clinical reference interval or diagnostic cut-point exists. The primary analysis assessed the Spearman correlation between α-Klotho and absolute eosinophil count; eosinophil percentage and the eosinophil-to-lymphocyte ratio were supportive measures. Robust linear regression estimated the percentage difference in α-Klotho per 1-standard-deviation increase in log-eosinophil count after adjustment for demographic, renal, hematological, smoking, and respiratory factors. Results: The median serum α-Klotho concentration was 1354.99 pg/mL (interquartile range 979.54-4047.59), and the median absolute eosinophil count was 0.14 ×10⁹/L (0.09-0.20). α-Klotho correlated positively with absolute eosinophils (Spearman ρ = 0.175; false-discovery-rate-adjusted q = 0.001), eosinophil percentage (ρ = 0.152; q = 0.004), and the eosinophil-to-lymphocyte ratio (ρ = 0.139; q = 0.008). In the fully adjusted model (n = 479), each 1-standard-deviation increase in log-eosinophils was associated with 22.3% higher α-Klotho (95% confidence interval 9.1-37.0%; p < 0.001). The association persisted after restricting α-Klotho to its 1st-99th percentiles (16.9% higher; 95% confidence interval 4.6-30.7%; p = 0.006) and after adjustment for study centre. Conclusion: Higher circulating α-Klotho was independently associated with higher absolute and relative eosinophil measures in this older Central Asian cohort. The direction differs from some population-based reports and should be considered hypothesis-generating. Prospective studies with eosinophil phenotyping, allergy and parasite assessment, and standardized α-Klotho assays are needed before the finding can be interpreted in relation to healthy longevity.

Abstract: A functional score is usually read as a property of the person measured. Increasingly it is produced by the person and an assistive environment together: a cane, a caregiver, a cueing system, a rehabilitation robot, or an artificial-intelligence system may supply part of it. The score is real. It answers a different question from the same score without the assistance.The distinction is not new. The International Classification of Functioning, Disability and Health separates capacity from performance in the current environment, with and without assistance. Motor learning has known for forty years that guidance raises performance during practice and lowers it on the unguided retention test. Rehabilitation separates the orthotic effect of a device from its therapeutic effect. Human factors describes the operator who performs better with automation and worse when it fails. These literatures rarely cite one another, and the rule has not been stated as a general principle across them.This paper states it. Assistance state is a condition of functional measurement, as supplemental oxygen is a condition of a six-minute walk. A score under one assistance state cannot be read as a change in what the person supplies when compared with a score under another, unless the change in assistance is what is studied. Where assistance is meant to leave the person more capable, the evaluation includes a prespecified assessment at a lower assistance state, a handback, under a criterion that does not move when the assistance does. Assistance state travels with the observation.

Abstract: Dissociative Identity Disorder (DID), formerly known as multiple personality disorder, is recognized as one of the most complex conditions in the fields of psychiatry and psychology. Initially associated with interpretations of demonic possession, it later came to be understood from a clinical perspective through the contributions of scholars such as Rush, Charcot, and Janet, who emphasized its dissociative nature. The former diagnostic category of hysteria was subsequently reorganized within modern psychiatric classification systems while preserving its underlying conceptual framework. Furthermore, widely publicized cases, such as The Three Faces of Eve and Sybil, contributed to strengthening the association between DID and early-life trauma. It is estimated that 1.5% of the Brazilian population is affected by DID. Between 2018 and 2023, Brazil's Ministry of Health recorded 3,667 cases. This study was conducted as a narrative, descriptive, and exploratory literature review, drawing on databases including Google Scholar, SciELO, and PePSIC, as well as scientific publications, using specific search descriptors related to dissociation and Dissociative Identity Disorder.

Abstract: Introductionː Embolization of middle meningeal artery (MMA) has become a minimally invasive alternative that can reduce the high rate of recurrence of chronic subdural hematoma (cSDH), but so far randomized evidence is scattered. To better explain its effectiveness and safety, we conducted a more recent meta-analysis of randomized controlled trials (RCTs). Evidence Acquisitionː A protocol in the PRISMA-2020 scheme was registered and PubMed, Embase, Cochrane CENTRAL, Scopus, ClinicalTrials.gov and WHO-ICTRP were searched via inception to 5 June 2025. RCTs focusing on adults alone with a comparison of MMA embolization (stand-alone, or adjunct to surgery) versus standard management were only eligible in this study. The pooled risk ratios (RRs) or standardized mean differences (SMDs) were created using random-effects models (DerSimonian–Laird) with Hartung–Knapp adjustment. The major endpoints were symptomatic recurrence (efficacy) and all-cause mortality (safety). Evidence Synthesisː Eight randomized controlled trials (RCTs) were included in this systematic review and quantitative synthesis (n = 1,862 patients). MMA embolization reduced symptomatic recurrence by approximately 47% compared to control (RR = 0.53; 95% CI: 0.39–0.73; I² = 0%; 95% prediction interval: 0.33–0.85; number needed to treat [NNT] = 14, 95% CI: 11–24). There was no significant benefit on good functional outcome (mRS ≤ 2) (RR = 1.01; 95% CI: 1.00–1.02; I² = 0%; 95% prediction interval: 0.93–1.10; three trials) or on independent functional outcome (mRS ≤ 3) (RR = 1.01; 95% CI: 1.01–1.02; I² = 0%; 95% prediction interval: 0.97–1.06; three trials) or on hematoma thickness reduction (SMD = –0.13; 95% CI: –0.35 to 0.09; I² = 42.4%; four trials, n = 1,467). All-cause mortality showed a non-significant trend toward reduction in the MMA embolization group (RR = 0.66; 95% CI: 0.38–1.16; I² = 23.4%; eight trials). Procedure-related complications were infrequent; the pooled complication rate across eight trials was approximately 1% (95% CI: 0–2%; I² = 23.6%; 95% prediction interval: 0–3%; 13 events in 964 patients), and no deaths were attributed to the embolization itself. The overall risk of bias across the included studies was low-to-moderate, and statistical heterogeneity was minimal across all key outcomes. Conclusionsː In summary, MMA embolization significantly reduces chronic subdural hematoma recurrence with a low complication rate, supporting its role as a safe adjunct to standard care. However, current evidence remains insufficient to confirm long-term functional, cognitive, or radiographic benefits, and further multicenter trials with standardized protocols and extended follow-up are essential.

Abstract: Background/Objectives: Obesity is a well-established risk factor for severe COVID-19, largely mediated by chronic inflammation originating from adipose tissue. The role of para-aortic adipose tissue (PAT)—a component of perivascular adipose tissue in COVID-19 severity remains poorly understood. This study aimed to investigate the association between PAT volume and the severity of acute SARS-CoV-2 infection and to evaluate its potential as a predictor of severe COVID-19. Methods: This retrospective single-center cohort study included 279 hospitalized patients with confirmed COVID-19 pneumonia. Based on disease severity, patients were divided into moderate and severe groups. PAT volume was measured around the aorta semi-automatically on a single chest computed tomography. Clinical, laboratory, and imaging data were analyzed. Logistic regression and receiver operating characteristic curve analysis were performed to assess the predictive value of PAT volume. Results: Patients with severe COVID-19 were significantly older, had higher body mass index. PAT volume differed significantly between groups, with a greater proportion of higher values in the severe group. Severe cases also exhibited significantly elevated levels of C-reactive protein, ferritin, and D-dimer, and lower oxygen saturation. Correlation analysis revealed significant associations between PAT volume and age, BMI, ferritin, the extent of lung involvement and SpO₂. Multivariable logistic regression confirmed that log-transformed PAT volume was independently associated with severe COVID-. The optimal threshold for initial PAT volume was 0.35 cm³ (sensitivity: 51.2%, specificity: 67.1%). Conclusions: PAT volume is independently associated with severe COVID-19, and values exceeding 0.35 cm³ may serve as a predictor of disease severity in hospitalized patients.

Abstract: Large language models can retrieve studies, synthesize evidence and support clinical decisions. This Review examines six overlapping domains and the evidence for their use. Improvements in individual tasks do not establish reliable syntheses or patient benefit. Across retrieval, synthesis, updating and clinical evaluation, the central challenge is to preserve source support, methodological judgment and patient context while testing whether the resulting workflow improves care.

Abstract: Background/Objectives: To compare static pelvic floor MRI morphometry between women with symptom-defined urinary incontinence (UI) and continent women and to examine whether observed differences persisted after accounting for parity and other clinical covariates. Methods: This retrospective cross-sectional comparative study included 131 women: 81 classified as having symptom-defined UI and 50 continent participants. UI classification was based on self-reported involuntary urinary leakage together with at least one positive response in the urinary distress domain of the PFDI-20; no urodynamic or objective continence test was used for study classification. Static 3.0-T pelvic MRI at rest was used to measure puborectalis thickness, genital hiatus dimensions, urethral morphology, obturator internus thickness, and rectus muscle thickness. Group comparisons, exploratory within-sample ROC analyses, and parsimonious logistic regression models were performed. Results: Women with symptom-defined UI had lower bilateral puborectalis thickness (left: 5.54 ± 1.59 vs. 6.76 ± 1.33 mm; right: 5.53 ± 1.67 vs. 6.51 ± 1.46 mm; p ≤ 0.001) and larger genital hiatus width (105.54 ± 15.97 vs. 93.07 ± 15.07 mm; p < 0.001) and area (median 396.9 vs. 308.1 mm²; p < 0.001). Urethral diameter was also greater (12.34 ± 1.91 vs. 11.60 ± 1.45 mm; p = 0.021). Discrimination was moderate for genital hiatus width (AUC = 0.720) and left puborectalis thickness (AUC = 0.730). In separate parity-adjusted models, hiatus dimensions and bilateral puborectalis thickness remained associated with UI. None retained statistical significance when age, BMI, parity, and multiple correlated morphometric measures were entered together in broader models. Conclusions: Women with symptom-defined UI showed differences in puborectalis thickness and genital hiatus dimensions on static MRI. These associations were evident in unadjusted and parity-adjusted analyses but were attenuated in broader multivariable models, indicating important confounding and shared variance with clinical factors. The exploratory thresholds were derived within this sample and should not be interpreted as diagnostic cut-offs. Static MRI morphometry may help characterize pelvic floor anatomy, but the present data do not support its use as a stand-alone diagnostic test for UI.

Abstract: Background: Left atrial (LA) strain monitored using speckle-tracking echocardiography has become an unobtrusive, sensitive measure of atrial performance and are used as an approximation of the left ventricular (LV) filling pressure. LA strain is in contrast to volumetric measurements and measures reservoir, conduit, and booster stage and can identify early impairment when the size of the LA is not observable. Hypertension is a significant risk factor in heart failure and is often not controlled resulting in a gradual cardiac remodelling and diastolic dysfunction. The cross-sectional studies have indicated that hypertensive subjects with normal LA volumes could already have lower LA reservoir and conduit strain and that non-dipper hypertension is linked to additional ones and harm to end-organs. Although these observations have been recorded, the incremental usefulness of LA strain to the prompt identification of cardiac dysfunction in patients with uncontrolled hypertension has not been indicated conclusively. Purpose: To determine whether strain of LA reservoirs offers any independent and early predictive values of subclinical cardiac dysfunction in patients with uncontrolled hypertension compared with controlled hypertension and normotensive controls. The study was a multicentre analytical cross-sectional research, which was carried out in three tertiary hospitals in Pakistan between April 2024 and March 2025. The adults between 30-75 years were sequentially enrolled and divided into uncontrolled hypertensive (uncontrolled BP on medication even with treatment) and controlled hypertensive (controlled BP on medication) or normotensive control groups. The exclusion criteria were structural heart disease, atrial fibrillation, receiving of valve disease or poor acoustic windows. The participants were subjected to ambulatory 24-h blood pressure monitoring, clinical evaluation and two-dimensional speckle tracking echocardiography. Off-line measurement of LA reservoir strain (LASr), conduit strain (LAScd) and contractile strain (LASct) were done based on the apical region on the four- and two-chamber views. According to the current guidelines regarding the diastolic functioning, early cardiac dysfunction was considered as high E/e; the E/e ratio exceeded 14 or LA volume index exceeded 34 ml/m2. Multivariate logistic regression used to determine the relationship between LASr and early dysfunction in the presence of age, sex, body-mass index, diabetes, systolic BP and LV ejection fraction. Findings: Out of 300 respondents (53 years old, mean age, 60 is men) there should be 100 participants who were uncontrolled hypertensives, 100 controlled and 100 normotensives. Systolic blood pressure (161 8 vs 132 10 vs 121 9 mmHg), body-mass index (28.154.39 vs 27.083.09 vs 24.023.33 kg/m 2 ) and LASr (22.359 vs 29.063 vs 34.270, p< 0.001) were higher in uncontrolled hypertensive patients. In uncontrolled, 92, in controlled and 16, in control subjects, early cardiac dysfunction was noted in 92, 56 and 16 per cent respectively. Lower LASr was independently tied to early dysfunction in multivariable analysis 0.91-0.99 p=0.010 ), higher systolic BP and body-mass index, and not age or sex, diabetes and ejection fraction. Conclusion: Speckle-tracking strain imaging (strain of the LA reservoir) is an autonomous predictor of early cardiac dysfunction in untreated hypertensive patients and provides an additional predictive value over blood pressure and traditional clinical variables. Periodic monitoring of LA strain can help to detect high-risk hypertensive patients with diastolic dysfunction sooner and start state-of-the-art disease-modifying treatments in time.

Abstract: Whole-exome sequencing (WES) is widely used to diagnose pediatric-onset inherited metabolic disorders (IEM), yet how often such patients carry more than one independent molecular diagnosis is rarely examined, particularly where testing is outsourced to commercial laboratories. We reviewed eight years (2018–2025) of outsourced WES at a Taiwanese pediatric genetics center. Of 227 referrals, 91 were solved, including 13 patients with pediatric-onset IEM or lysosomal storage disease; all variants were reannotated against ACMG/AMP criteria. Eighteen molecular diagnoses supported by 27 variants were established. Five of 13 patients (38.5%; exact 95% CI 13.9–68.4%) carried two independent molecular diagnoses, nearly eight times the 4.9% multi-locus rate of large unselected exome series and 3.9 times the 9.9% in our overall cohort; the proportion stayed above both benchmarks under progressively stricter counting rules, falling to 7.7% when pathogenic or likely pathogenic variants were required at both loci. Multi-locus cases typically paired a primary IEM with an unrelated Mendelian disorder. Disease-specific therapy was initiated in 8 of 13 patients (61.5%). In selected pediatric-onset metabolic disorders a single molecular diagnosis may not fully explain the presentation, underscoring the need for comprehensive variant interpretation and periodic reanalysis.

Abstract: Ultrasound is a widely used imaging modality in clinical practice, and sonographic signs serve as valuable teaching tools that aid in pattern recognition and diagnosis. This review consolidates five novel sonographic signs previously proposed by the author, including the Cracked Earth Sign for subcutaneous edema, the Mushroom Cap Sign for localized gallbladder adenomyomatosis, the LTS Sign for dilated cardiomyopathy, the LTI Sign for endocardial fibroelastosis, and the Three Pipes Sign for the suprasternal long-axis view of the aortic arch, spanning the fields of superficial ultrasound, abdominal ultrasound, and echocardiography. For each sign, its naming logic, definition, clinical implications, and teaching value are described. This review aims to facilitate a better understanding of these signs and to promote their use as teaching aids in ultrasound education.

Abstract: Risk stratification in severe trauma remains a major clinical challenge: standard trauma scores (Injury Severity Score, ISS; Trauma and Injury Severity Score, TRISS) rely on anatomical and physiological data but lack metabolic components, potentially underestimating risk in haemodynamically compensated patients with underlying derangements. Alactic Base Excess (ABE) isolates the non-lactic fraction of metabolic acidosis by correcting base excess for lactate. We conducted a retrospective cohort study using the MIMIC-IV v3.1 database, including adult trauma patients with an ISS ≥16 and an arterial blood gas measurement within two hours of admission (n=134), to assess ABE’s independent and incremental prognostic value for in-hospital and 30-day mortality, handling missing covariates by multiple imputation (m=20). ABE was independently associated with in-hospital mortality after adjustment for age, New ISS (NISS), and mechanism of injury (odds ratio 0.84; 95% CI 0.745–0.946; p=0.004; AUC 0.643), and improved model fit beyond a clinical base model (p=0.002) and beyond TRISS (p=0.029), with no significant miscalibration. Findings were consistent for 30-day mortality and substantially stronger in a 60-minute sensitivity cohort (n=54; AUC 0.803; negative predictive value 95.5%). ABE offers modest incremental prognostic value beyond established trauma scores; its immediate availability from a routine blood gas positions it as a practical early adjunct at a point where no composite score is yet computable.

Abstract: Chronic non-communicable diseases (NCDs) represent the greatest medical challenge of the 21st 2 century. Eighty percent of the etiology of chronic diseases is non-genetic. Chronic diseases are not 3 monogenetic, static defects, but rather the expression of disturbed regulatory processes within the 4 body’s biological memory systems — metabolic, immunological, and neuronal. This framework 5 understands health as a dynamic state of functional energy allocation and adaptive plasticity, which 6 can be regulated through epigenetic, mitochondrial, and neuroendocrine mechanisms. It connects 7 modern systems biology with the principles of behavioral and neuropsychology and proposes that 8 self-efficacy, coherence, and voluntariness function not merely as ethical ideals but as biologically 9 supportive conditions for healing. Emerging evidence suggests that targeted habitual interventions 10 can induce profound changes in gene expression, mitohormesis, and immune regulation, potentially 11 making epigenetically fixed disease patterns partially reversible. By integrating molecular biology, 12 behavioral science, and mentor-based formats, this system aims to bridge the gap between biomedical 13 knowledge and effective patient care. This paper proposes an integrative theoretical framework: 14 regeneration is understood not as a passive process but as an active learning process of the organism. 15 Healing arises when biological, psychological, and social systems are brought into coherent resonance. 16 In this sense, this proposed system forms the bridge between molecular biology, lifestyle research, and 17 human experience — with the goal of not merely measuring health, but consciously cultivating it.

Abstract: Background: Primary hyperparathyroidism (PHPT) is most commonly caused by a solitary parathyroid adenoma, whereas compressive symptoms from large adenomas are uncommon. This report describes an unusual presentation with dysphagia. Methods: A 66-year-old woman with one month of progressive dysphagia and approximately 10 kg of weight loss underwent gastroenterological and otorhinolaryngological assessment, contrast-enhanced computed tomography, ultrasonography, biochemical testing, and parathyroid hormone (PTH) washout. Results: Endoscopy and flexible fiberoptic examination did not identify a cause of dysphagia. CT demonstrated a 3.0 × 1.9 × 4.7 cm heterogeneous cervical mass extending toward the superior mediastinum and displacing adjacent structures. Total calcium was 3.02 mmol/L, ionized calcium 2.60 mmol/L, and serum PTH 365.1 pg/mL. PTH washout exceeded 3438 pg/mL. Surgical excision and histopathology confirmed a parathyroid adenoma. Postoperative PTH decreased to 58.4 pg/mL and dysphagia resolved completely. Conclusions: A large parathyroid adenoma should be considered in patients with unexplained dysphagia, particularly when hypercalcemia and elevated PTH are present.

Abstract: Background/Objectives: Degenerative lumbar spondylolisthesis is first assessed on standing lateral radiographs, yet the slip is still measured in millimeters or graded semi-quantitatively, both dependent on magnification, calibration and reader experience. We introduce quadrilateral segmental analysis (QSA), a calibration-free geometric method for detecting anterolisthesis. Methods: In 50 patients from the PROGRES cohort, a blinded observer drew the L1–S1 superior endplate lines on standing radiographs; an automated pipeline computed the diagonal ratio K for each quadrilateral formed by adjacent lines. The reference standard was adjudicated two-radiologist classification (κ = 0.916). After excluding 90 retrolisthetic segments, 160 segments were analyzed by receiver operating characteristic analysis with patient-cluster bootstrap, a 61-threshold sweep of K and cross-validated logistic models. Results: Anterolisthesis was present in 54 segments (33.8%). K discriminated well (area under the curve [AUC] 0.892, 95% CI 0.841–0.937): K ≤ 0.85 confirmed a slip (specificity 99.1%, positive predictive value [PPV] 96.0%) and K > 0.95 excluded it (sensitivity 100%, negative predictive value [NPV] 100%). Rounded to one decimal, K defined three tiers that classified 46.9% of segments without error (K < 0.9: PPV 100%; K = 1.0: NPV 100%). Conclusions: Quadrilateral segmental analysis (QSA) converts vertebral translation into an angular signature readable from a single standing lateral radiograph without calibration. K (the diagonal ratio) translates the radiologist's assessment of anterolisthesis into a single number. QSA is simple enough for routine reporting and fully automatable. Reliability testing, external validation and extension to dynamic image pairs are the next steps.

Abstract: Mechanically ventilated ICU patients face vulnerability, disorientation, loss of control, and reduced communication. We report two later phases of an iterative program testing positive suggestion-based psychological support. Study 3 randomized 112 adults to standard care, audio-recorded positive suggestions (ARPS), or ARPS plus reduced-frequency live positive suggestion-based psychological support (PSBPS); Study 4 randomized 35 patients to standard care or reduced-frequency live PSBPS. Primary outcomes were mechanical ventilation (MV) duration and ICU length of stay (LOS). In Study 3, neither intervention significantly reduced MV duration or ICU LOS in the full randomized sample. Planned sex-stratified analyses showed 63.69 fewer MV hours among female ARPS patients than female controls, but treatment-by-sex interaction was nonsignificant. Exploratory post hoc engagement analyses yielded a hypothesis-consistent pattern: consistently engaged ARPS patients had approximately 1.7 days shorter MV and 2.8 days shorter ICU LOS than controls, while HEG patients had longer courses. In Study 4, live PSBPS reduced MV duration by 76.62 hours (95% CI [1.07, 152.16]; p = 0.047), supported by nonparametric, SAPS II-adjusted, and competing-risk sensitivity analyses; ICU LOS was nonsignificantly shorter by 51.45 hours. Mortality was numerically lower in intervention groups but nonsignificant. These historical randomized findings support confirmatory evaluation of coherent, acceptable PSBPS delivery in contemporary ICU care.

Abstract: Background/Objectives: Inpatient fall risk evolves during hospitalization and may not be adequately represented by admission-based assessment alone. Although assessments obtained closer to fall events can outperform admission scores, less is known about how fall-risk trajectories differ between patients who fall and those who remain fall-free. This study characterized temporal changes in Hendrich II scores, compared risk trajectories between fall cases and temporally aligned controls, and identified factors associated with risk escalation. Methods: We conducted a retrospective matched case-control study using routinely collected inpatient data from a tertiary care hospital. Fall cases were matched to nonfall controls by admission date with temporally aligned event/index assessments. Change in risk (ΔScore) was calculated as the event/index score minus the admission score. Logistic regression evaluated associations with falls, and receiver operating characteristic analysis compared discrimination at admission and event/index time. Results: Among 10,407 encounters (276 falls and 10,131 controls), fall cases had higher admission Hendrich II scores than controls (6.66 vs. 3.27). In the temporally aligned subset, scores increased substantially among fall cases but remained relatively stable among controls (mean ΔScore, +2.55 vs. −0.20; p < 0.001). Each 1-point increase in ΔScore was associated with 69% higher odds of falling (OR, 1.69; 95% CI, 1.57–1.83). Event-time factors independently associated with falls included confusion, elimination problems, antiepileptic medication use, and moderate mobility impairment. Discrimination increased from admission (AUC, 0.724) to event time (AUC, 0.831; p < 0.001). Conclusions: Patients who experienced inpatient falls demonstrated substantial escalation in Hendrich II risk not observed among temporally aligned controls. Monitoring score trajectories may provide clinically useful information beyond admission screening and warrants prospective evaluation as a strategy for guiding fall-prevention interventions.

Abstract: Background: Lupus nephritis (LN) remains a major cause of morbidity among patients with systemic lupus erythematosus, and treatment resistance continues to pose clinical challenges. Calcineurin inhibitors (CNIs), including tacrolimus (TAC) and voclosporin (VCS), have emerged as adjuncts to standard induction therapy. This systematic review and meta-analysis identified and quantified the randomized evidence for TAC and for VCS as induction therapy in LN, summarizing the pooled effect of each agent against its trial comparators, with an exploratory adjusted indirect comparison provided for hypothesis generation. Methods: Following PRISMA guidelines, a comprehensive literature search was conducted through June 2025. Eligible studies were randomized controlled trials enrolling adults with biopsy-proven active class III, IV, or V LN and reporting complete or partial renal response after TAC- or VCS-based therapy. Pooled risk ratios (RRs) were calculated using a random-effects model, and an indirect Bucher comparison was performed. Results: Five multinational randomized controlled trials, including 1,433 participants, were analyzed. TAC significantly improved renal response compared with conventional induction therapy (RR, 1.36; 95% CI, 1.00–1.86; p = 0.048), with substantial heterogeneity (I² = 73%). VCS also significantly improved renal response (RR, 1.78; 95% CI, 1.35–2.34; p < 0.0001), with low heterogeneity (I² = 0%). Indirect comparison showed no statistically significant difference between TAC and VCS (RR, 0.79; 95% CI, 0.58–1.09; p = 0.08). Conclusion: Both TAC-based and VCS-based induction increased renal response relative to their respective comparators. A valid formal head-to-head comparison is not currently possible because the two evidence sets do not share a common comparator, and the exploratory indirect comparison showed no significant difference between agents. Choice between these agents should therefore rest on safety, tolerability, cost, and patient context rather than on a demonstrated efficacy advantage. Dedicated network meta-analyses address the broader treatment network in more formal terms.

Abstract: Echocardiography is an important imaging modality in the assessment of cardiovascular diseases. Several echocardiographic signs have been described to aid in the diagnosis of specific clinical conditions and to help clinicians remember the key sonographic features. This review summarizes five classic signs in echocardiography, including the McConnell's Sign, the D-Sign, the 60:60 Sign, the SAM Sign, and the Swinging Heart Sign, as well as three novel signs, the Three Pipes Sign, the LTS Sign, and the LTI Sign. This review aims to provide an overview of the classic echocardiographic signs, focusing on their naming logics, definitions, and clinical implications to facilitate a better understanding of them, and to first propose three novel signs, the Three Pipes Sign, the LTS Sign, and the LTI Sign, which may aid in diagnosis and serve as teaching aids in echocardiography.

Abstract: A patient whose average performance clears a fixed absolute criterion while individual performances fall below it is at risk on those occasions, and this paper proposes that the frequency of those crossings is the clinical meaning of dispersion in serial functional measurement. Serial functional measurement currently yields two statistics: the level of performance and its trajectory. This paper argues that a third — the dispersion of performance across serial identical challenges — carries clinical information that the first two are constructed to discard, and predicts that the three are separably estimable, with dispersion adding predictive value once level and trajectory are both in the model. The argument rests on a threshold logic: functional risk is realized not at the mean but in the trough, because falls, decompensations, and failed activities of daily living occur on bad days. High dispersion therefore means two things at once: that any single measurement is an unreliable estimate of the patient, and that the patient is nearer the threshold than any single measurement can show. A published precedent exists in a different variable: visit-to-visit blood pressure variability predicts stroke independently of mean pressure, with predictive strength increasing with the number of measurements, and treatments that improved the mean while worsening the dispersion produced worse outcomes. The structure transfers to functional reserve with one inversion — for blood pressure the danger is the peak; for reserve it is the trough. Estimating the quantity requires the task criterion to be held fixed in absolute terms across serial challenge; a criterion that moves with the patient absorbs the dispersion it is supposed to reveal. The construct is proposed, not validated; the conditions that would defeat it are stated.

Abstract: Functional reserve is treated here as a latent physiological construct. Under controlled challenge its measurable phenotype is rate asymmetry—the ratio of restoration rate to degradation rate within a domain. The proposed estimator is ρ_d = r_g / r_l, formed only when both rates are fitted constants obtained from the same instrument in identical units. The primary quantity is the minimum of the point estimates across eligible domains; uncertainty is reported separately as a bootstrap or simultaneous interval for that minimum. Mandatory core domains (force recovery, lactate clearance, dual-task cost recovery) are required for cross-person comparison and are reported with the domain count.On the acute cycle the model predicts ρ < 1: parallel multi-factorial degradation outruns sequential, energy-constrained restoration. Net adaptation occurs later, outside the measured window. The governing domain—the eligible domain with the smallest ρ_d—identifies the recovery bottleneck under the specified challenge. Intensity is measured, volume is measured, frequency is inherited.The construct shares formal structure with a companion single-domain definition formed over weeks, but operates at a different timescale and reflects different physiology.