Search Results (1,232)

Epstein–Barr virus (EBV) contributes to human immunodeficiency virus (HIV)-associated diffuse large B-cell lymphoma (DLBCL) pathogenesis. We retrospectively analyzed clinical features and outcomes of EBV-positive (n = 32) and -negative (n = 71) cases. EBV status was determined using in situ hybridization. Immunological parameters, histological subtype, systemic B symptoms, plasma EBV DNA, and response to therapy were examined. Survival was compared using Kaplan–Meier analysis. Factors associated with overall survival (OS) and progression-free survival (PFS) in EBV-positive patients were examined using Cox regression models. EBV-positive cases showed a higher proportion of non-germinal center B cell subtypes and B symptoms, higher circulating EBV viral loads, and lower CD4⁺ T-cell counts at diagnosis than EBV-negative cases. OS did not differ significantly within the full cohort but was shorter in EBV-positive cases with high International Prognostic Index scores or CD4⁺ T-cell counts ≥ 50 cells/$\mathsf{\mu }$L. Concurrent infections and elevated plasma EBV DNA levels remained associated with unfavorable survival outcomes. EBV-positivity in HIV-associated DLBCL is related to more aggressive clinical and immunological features and independently predicts poorer survival outcomes in high-risk subgroups. Plasma EBV DNA may reliably indicate EBV status and serve as a prognostic biomarker. Integrating these features into clinical decision-making may enhance risk stratification and inform individualized treatments. Full article

Background and Objectives: Major burn injury causes systemic immune dysregulation and increases susceptibility to infectious complications. While poor oral health is a potential reservoir for respiratory pathogens, its impact on burn patients—who often require repeated airway manipulation—is not well-defined. This study investigated the association between preoperative dental status and postoperative pneumonia in patients undergoing burn surgery. Materials and Methods: We conducted a retrospective cohort study of 894 adult patients (≥19 years) admitted to a burn intensive care unit (ICU) between 2015 and 2024. Preoperative dental status was categorized as favorable or unfavorable (≥2 missing teeth, loose teeth, or fractured teeth). The primary outcome was 30-day postoperative pneumonia. Secondary outcomes included 90-day hospital-free days and ICU-free days. Results: Postoperative pneumonia occurred in 294 patients (32.9%). The incidence of postoperative pneumonia was 47.7% among patients with unfavorable preoperative dental status, compared with 31.2% among those with favorable preoperative dental status (p < 0.001). In multivariable analysis, unfavorable dental status was an independent predictor of 30-day pneumonia (odds ratio, 1.681; 95% confidence interval, 1.084–2.599; p = 0.018). Patients with unfavorable status also had significantly fewer 90-day hospital-free days (9 vs. 22 days, p = 0.034) and ICU-free days (65 vs. 68 days, p = 0.012). Conclusions: Unfavorable preoperative dental status is independently associated with an increased risk of postoperative pneumonia and poorer clinical recovery in burn patients. Routine dental assessment may serve as a simple tool for perioperative risk stratification in patients undergoing burn surgery. Full article

Objectives: Virtual reality (VR) enables controlled, interactive, and ecologically valid visual tasks, offering potential advantages over static clinical tests. This systematic review synthesized current evidence on the use of VR technologies for assessing visual capacities across ocular, neurological, and low-vision populations, with particular attention to technological approaches, clinical domains, methodological quality, safety, and future translational needs. Methods: Following PRISMA 2020, PubMed, Scopus, and Web of Science were searched from inception to 2 August 2025, using database-specific strategies for virtual reality and visual function. Three reviewers independently screened reports, extracted data, and appraised completed studies using design-appropriate NIH Study Quality Assessment Tools or Cochrane Risk of Bias 2 Owing to methodological heterogeneity, findings were synthesized narratively. The review was not registered and no protocol was prepared. Results: Of 364 records, 36 completed studies met the eligibility criteria and were included in the narrative synthesis (publication years 2014–2024); one additional randomized-trial protocol was catalogued separately as ongoing evidence. Most completed studies employed immersive head-mounted displays, while others used semi-immersive or desktop VR. Assessed domains included visual fields, visual acuity, contrast sensitivity, oculomotor and vergence function, postural control, functional navigation, spatial orientation, and obstacle avoidance. The most mature evidence concerned VR-based perimetry and functional visual assessment in glaucoma and low-vision populations. Reported adverse events were uncommon and mild, mainly transient cybersickness, dizziness, or visual discomfort. Among completed studies, methodological appraisal was favorable for 10, intermediate for 25, and unfavorable for 1. Overall, evidence supports feasibility, user acceptability, and convergent validity versus selected conventional tools, but substantial heterogeneity remains in hardware, calibration, exposure duration, outcome metrics, and follow-up. Conclusions: This systematic review highlights the growing role of VR in assessment, showing potential for controlled, ecologically oriented evaluations across domains like perimetry and functional vision. While promising, VR is currently a complementary framework rather than a replacement for established clinical tools, requiring stronger validation, repeatability testing, and calibration standardization for routine implementation. Full article

Background: Clear cell renal cell carcinoma (ccRCC) is characterized by marked molecular heterogeneity, aggressive clinical behavior, and prominent angiogenesis, highlighting the need to better understand the functional regulators underlying tumor progression and vascular remodeling. OTOF has previously been reported as a prognostically relevant gene in ccRCC; however, its biological function and potential involvement in tumor angiogenesis remain unclear. Methods: In the present study, we investigated the biological and pro-angiogenic roles of OTOF and explored the signaling pathways potentially involved. Results: Analysis of the TCGA-KIRC cohort confirmed that elevated OTOF expression was associated with unfavorable clinical outcomes. Functional experiments demonstrated that OTOF knockdown suppressed ccRCC cell proliferation, migration, and invasion and inhibited xenograft tumor growth. OTOF depletion also reduced intratumoral vascularization and impaired the ability of ccRCC cell-conditioned medium to promote HUVEC tube formation. Mechanistically, OTOF knockdown decreased VEGFA levels and was accompanied by reduced AKT phosphorylation and suppression of downstream HIF/VEGFA signaling. Pharmacological modulation of AKT signaling and VEGFA add-back experiments further supported the functional involvement of the AKT/HIF/VEGFA pathway in OTOF-associated angiogenesis. Conclusions: These findings extend previous observations regarding the prognostic relevance of OTOF by providing functional and mechanistic evidence that OTOF contributes to ccRCC progression and angiogenesis, at least in part, through AKT-dependent HIF/VEGFA signaling. Full article

Medication-related osteonecrosis of the jaws (MRONJ) remains a challenging complication associated with antiresorptive therapy, highlighting the need for effective adjunctive preventive strategies. This study evaluated the effects of systemic ozone therapy, alone or combined with topical 10% metronidazole paste or 2% chlorhexidine gel, on alveolar repair in a zoledronate-induced rat model of MRONJ. Forty-two ovariectomized female Wistar rats were allocated into seven experimental groups. Following mandibular first molar extraction, animals received systemic ozone therapy and/or topical antimicrobial treatment according to the experimental protocol. Clinical, histomorphometric, micro-computed tomography (micro-CT), Picrosirius Red, and immunohistochemical analyses were performed. Zoledronate treatment markedly impaired alveolar repair, resulting in reduced new bone formation, increased non-vital bone, epithelial disorganization, and unfavorable bone microarchitecture. Systemic ozone therapy significantly increased new bone formation and improved bone microstructural parameters compared with untreated zoledronate animals. Ozone-treated groups also exhibited more organized collagen fibers and increased VEGF and osteocalcin immunostaining. Topical metronidazole and chlorhexidine were associated with favorable tissue repair findings, while combined therapies showed more favorable outcomes than zoledronate treatment alone. These findings suggest that systemic ozone therapy, particularly when associated with topical antimicrobial treatments, improves alveolar repair and represents a promising adjunctive strategy for preventing MRONJ. Full article

Background/Objectives: Incretin-based pharmacotherapies are the most effective non-surgical treatments for obesity to date, yet 85% of patients discontinue within the second year of real-world use. No established framework exists for managing this post-cessation transition. This narrative review evaluates the evidence for structured exercise to mitigate physiological rebound and support long-term weight management following discontinuation. Methods: A narrative review was conducted per Assessment of Narrative Review Articles (SANRA) guidelines using PubMed, Scopus, and Web of Science from January 2005 through to June 2026. Results: Post-cessation weight regain averages 5.6 kg within one year and is observationally associated with dose-dependent cardiometabolic worsening. Lean mass losses averaging 6–7 kg and reductions in bone mineral density are seen during active treatment, creating a metabolically unfavorable state at cessation compounded by fat-preferential regain. Exercise and pharmacotherapy generate fundamentally different body composition outcomes. Exercise preserves lean mass, bone density, cardiorespiratory fitness, and insulin sensitivity, while pharmacotherapy alone does not, with downstream implications for resting metabolic rate and post-cessation rebound. Controlled trial data show exercise initiated during incretin treatment is associated with significantly less weight regain, greater sustained weight loss, and maintained physical activity levels one year after medication and supervised program end. This evidence derives from a single liraglutide-based trial and may not generalize directly to semaglutide, tirzepatide, or next-generation agents. Real-world data associate exercise counseling with durable weight loss after discontinuation. Conclusions: No randomized controlled trial has directly evaluated exercise at pharmacotherapy cessation; conclusions are based on post-treatment extension, real-world observational, and mechanistic evidence. Combined aerobic and resistance training is a biologically plausible, low-risk adjunct to incretin-based pharmacotherapies. Resistance training, adequate dietary protein, and individualized clinical screening are likely important components pending direct evidence from post-cessation trials. Full article

Melatonin has chronobiotic, antioxidant, anti-inflammatory, and neuromodulatory properties, and its oral effects may vary according to formulation. This study compared conventional melatonin with a lipid-multiparticulate (LMP) formulation in two acute pharmacological mouse paradigms. Eighty-four male BALB/c mice were assigned to caffeine-evoked cortical activity or pentobarbital-induced sedative-hypnotic experiments. Mice received caffeine (7.5 mg/kg, i.p.) alone or with standard or LMP-melatonin (10 or 20 mg/kg, oral). ECoG recorded cortical electrical activity under urethane anaesthesia. In a separate cohort, latency to and duration of pentobarbital-induced loss of the righting reflex were measured. Circulating neurochemical and redox markers, as well as neurotransmitter- and inflammation-related gene and protein expression, were evaluated. Caffeine increased spike frequency and altered ECoG amplitude, together with unfavorable changes in circulating neurochemical and redox markers and in neurotransmitter receptor- and inflammation-related outcomes. Both melatonin formulations attenuated several of these changes in a dose-dependent manner, with the strongest effects generally observed in the high-dose LMP-melatonin group. Compared with conventional melatonin, LMP-melatonin produced greater modulation of ECoG activity, circulating biochemical markers, neurotransmitter-receptor expression, and IL-6 and TNF-α-related outcomes. LMP-melatonin also produced a greater reduction in the latency to and a greater prolongation of the duration of pentobarbital-induced loss of the righting reflex. LMP-melatonin produced greater formulation-dependent effects than conventional melatonin on caffeine-evoked cortical electrical activity, pentobarbital-induced sedative-hypnotic responses, and selected biochemical and molecular outcomes. However, pharmacokinetic exposure, physiological sleep stages, sleep architecture, sleep quality, and direct measures of neuronal injury were not assessed. Therefore, the findings do not directly establish enhanced bioavailability, physiological sleep promotion, or neuroprotection. Full article

Background/Objectives: SPINEHealthie is a smartphone-based application enabling remote patient monitoring, care delivery and standardized collection of patient-reported outcome measures (PROMs). This registry-based analysis evaluates patient satisfaction with the platform across a large, heterogeneous spine surgery cohort. Methods: A total of 1729 thoracolumbar spine surgery cases were eligible for analysis. Among these, 881 (50.9%) completed the in-app feedback survey and constituted the primary feedback cohort. The global app experience was categorized as “Very Good” or “Poor”. Clinical outcomes, i.e., the Visual Analogue Scale (VAS) for back and leg pain and the Oswestry Disability Index (ODI) were assessed at baseline and in the postoperative period; Δ denotes the change from baseline to two weeks postoperation. Results: Among feedback responders, 800 patients (90.8%) rated their app experience as “Very Good”, while 80.8% of 639 patients with surgical outcome data reported that the surgery met their expectations. However, app experience and surgical outcome expectations were assessed using different items at different postoperative time points. Among patients whose surgery did not meet expectations, 84.6% rated their app experience as “Very Good”. Patients with a “Very Good” app-experience rating demonstrated significantly greater improvement in back pain (ΔVAS Back pain 2.94 vs. 2.13, p = 0.027), leg pain (ΔVAS Leg pain 3.16 vs. 2.14, p = 0.019) and disability (ΔODI 11.00 vs. 2.41, p < 0.001). In the primary model, older age, shorter follow-up duration and smaller ODI improvement were associated with an unfavorable app experience; only the association with age remained consistent across sensitivity analyses. Conclusions: Among feedback responders, SPINEHealthie was associated with a high proportion of favorable global app-experience ratings. Favorable app-experience ratings remained high, even among patients with unmet surgical expectations or failure to achieve the exploratory two-week ODI-improvement threshold, suggesting that perceived platform value is not solely explained by surgical outcome. Older patients and those with limited functional recovery were identified as subgroups that may benefit from targeted onboarding and engagement strategies. Full article

Background/Objectives: Digoxin, a positive inotropic agent with a narrow therapeutic window, is used in heart failure but carries toxicity risks. This study aims to characterize the profile of digoxin-associated adverse drug reactions reported in the EudraVigilance database, focusing on drug–drug interactions, dosing errors, and off-label use. Methods: Descriptive and disproportionality analyses were performed on Individual Case Safety Reports (ICSRs) until 25 January 2026. Digoxin was compared with other inotropic agents by calculating the Reporting Odds Ratio and 95% confidence intervals. Results: Digoxin recorded 11,426 ICSRs, with a predominance in patients aged 65–85 years (46.4%) and over 85 years (25.1%). Higher reporting probabilities were identified for the terms “Drug interaction” and “Overdose” compared to other inotropes. Fatal outcomes were reported in 19 cases related to drug interactions and 41 cases related to overdose. Consistent disproportionality signals were found for gastrointestinal, renal, and nervous system disorders. Off-label use was reported in 0.8% of cases and was associated with unfavorable clinical outcomes. Risks are exacerbated by polypharmacy and renal decline in elderly patients. Conclusions: Digoxin toxicity and cardiac complications are the primary drivers of reported morbidity. This risk profile highlights the need for the rigorous clinical monitoring, precise dose adjustments and heightened vigilance regarding drug–drug interactions. Full article

Background/Objectives: Metabolic dysregulation has emerged as a potential modifier of disease activity and disability in multiple sclerosis (MS). However, the relationship between glycemic status and clinical outcomes in patients with MS remains incompletely understood. This study aimed to investigate the associations of glycemic regulation with disease severity, relapse activity, inflammatory markers, and metabolic characteristics in patients with MS. Methods: In this retrospective single-center observational study, 455 patients with MS aged 18–65 years were included. Patients were categorized into normoglycemia (n = 241), prediabetes (n = 98), and diabetes (n = 116) according to American Diabetes Association criteria and documented diabetes diagnosis. Demographic characteristics, Expanded Disability Status Scale (EDSS) scores, annualized relapse rate (ARR), disease-modifying therapy (DMT), hematological indices, inflammatory markers, and metabolic parameters were retrieved from electronic medical records. Associations between glycemic status and clinical outcomes were evaluated using group comparisons, Spearman correlation analyses, and multivariable linear regression models. Results: Significant differences were observed among glycemic groups for age, disease duration, EDSS score, ARR, MS phenotype, platelet count, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), lipid parameters, estimated glomerular filtration rate, alanine aminotransferase, gamma-glutamyl transferase, triglyceride–glucose (TyG) index, and atherogenic index of plasma (all p < 0.05). HbA1c, FPG, TyG index, lipid parameters, CRP, and ESR were positively correlated with EDSS scores (all p < 0.05). In contrast, these markers showed inverse correlations with ARR. However, after adjustment for demographic and clinical variables, including age, sex, disease duration, MS phenotype, and disease-modifying therapy (DMT), neither prediabetes nor diabetes remained independently associated with disability, as measured by the EDSS score, or with ARR. Progressive MS phenotype, older age, and longer disease duration were independently associated with higher disability, whereas age, disease duration, and progressive phenotype were independently associated with lower ARR. Conclusions: Impaired glycemic status is associated with greater disability, unfavorable metabolic profiles, and increased systemic inflammation in patients with MS. Nevertheless, glycemic status was not independently associated with disability or relapse activity after adjustment for major clinical confounders. These findings suggest that metabolic dysregulation accompanies more severe clinical characteristics but may not independently drive disease progression in MS. Full article

Background: Prognostic assessment in patients undergoing surgical treatment for acute extra-axial hematomas remains challenging. Most available prognostic models have been developed in heterogeneous populations of patients with traumatic brain injury, while relatively few studies have focused exclusively on surgically treated patients with acute subdural hematoma (ASDH) and epidural hematoma (EDH). Although mortality has been widely investigated, less attention has been paid to early functional recovery after surgery. This study aimed to identify clinical, physiological, laboratory, and radiological factors associated with early functional outcome three months after surgery in this patient population. Methods: We retrospectively analyzed 181 consecutive patients who underwent surgical treatment for acute extra-axial hematomas at two neurosurgical centers. Demographic, physiological, laboratory, and radiological variables recorded on admission were evaluated. Functional outcome was assessed three months after surgery using the Glasgow Outcome Scale (GOS). Favorable outcome was defined as GOS 4–5 and unfavorable outcome as GOS 1–3. Independent prognostic factors were identified using multivariable logistic regression analysis. Results: An unfavorable outcome was observed in 105 patients (58.0%). Multivariable analysis identified higher admission GCS score as the strongest independent predictor of a favorable functional 3-month outcome (OR = 1.45, 95% CI: 1.27–1.65; p < 0.001). The presence of an epidural hematoma (OR = 5.77, 95% CI: 1.36–24.47; p = 0.018) was also independently associated with a favorable functional outcome. Conversely, traumatic subarachnoid hemorrhage (OR = 0.19, 95% CI: 0.07–0.52; p = 0.001), hyperglycemia (OR = 0.20, 95% CI: 0.05–0.78; p = 0.020), and low hemoglobin levels (reference: normal hemoglobin; OR = 0.18, 95% CI: 0.06–0.54; p = 0.002) were associated with a lower likelihood of favorable functional outcome. Conclusions: Admission neurological status, represented by the GCS score, was the strongest predictor of 3-month functional outcome in patients undergoing surgical treatment for acute extra-axial hematomas. Hematoma type, hemoglobin level, traumatic subarachnoid hemorrhage, and hyperglycemia were also independently associated with outcome. These findings may improve early prognostic assessment; however, because of the retrospective study design and the lack of external validation, they should be interpreted with caution. Full article

Objective: To analyze, through a systematic review with meta-analysis, the acute effects of warm-up based on different types of stretching on physical performance in soccer players. Methods: The PRISMA guidelines were followed, and the protocol was registered in PROSPERO. The search was conducted in PubMed, MEDLINE, CINAHL Complete, Scopus, SPORTDiscus, and Web of Science through June 2026. We included randomized and non-randomized controlled trials comparing warm-ups involving static, dynamic, or ballistic stretching against conventional warm-ups or active controls in healthy soccer players. Methodological quality was assessed using TESTEX, risk of bias using RoB 2, and certainty of evidence using GRADE. Effects were calculated using Hedges’ g with random-effects models. Results: Six studies were included, resulting in a limited evidence base. Different types of stretching were reported, with dynamic stretching producing favorable effects on countermovement jump performance compared with control conditions (ES = 0.555; 95% CI: 0.306 to 0.804; p < 0.001) and on 10 m sprint performance (ES = 0.397; 95% CI: 0.191 to 0.603; p < 0.001). For the 30 m sprint, dynamic stretching showed a favorable but non-significant effect (ES = 0.328; 95% CI: −0.258 to 0.914; p = 0.273), with substantial heterogeneity. Dynamic stretching also showed a favorable but imprecise and non-significant effect on dominant-foot ball-kicking speed (ES = 2.496; 95% CI: −2.240 to 7.232; p = 0.302). Ballistic stretching improved countermovement jump performance compared with control conditions (p < 0.001), whereas static stretching showed trivial, inconsistent, or unfavorable effects, including a small adverse effect on 10 m sprint performance (ES = −0.209; 95% CI: −0.398 to −0.019; p = 0.031). Heterogeneity ranged from moderate to substantial, and the GRADE certainty of evidence was low because of serious risk of bias and inconsistency. Conclusions: Dynamic stretching may acutely improve selected explosive performance outcomes in soccer players; however, the low certainty of evidence and substantial heterogeneity preclude definitive recommendations. Full article

Background/Objectives: Endovascular embolization of ruptured intracranial arterial aneurysms has become the first-choice treatment due to its minimal invasiveness, rapid patient recovery, and lower complication rate. The aim of this study was to analyze putative risk factors of unfavorable outcomes of ruptured intracranial aneurysms after coil embolization and the recanalization rate. Methods: This case series included adult patients with ruptured intracranial aneurysms who underwent endovascular embolization during the study period of 2007–2023. In total, 1080 patients with ruptured intracranial aneurysms treated using endovascular coiling participated in this study. Results: During the first year after the initial intervention, repeated embolization was performed for 50 patients (5.5%). Treatment outcome was assessed using the modified Rankin Scale, and neuroradiological follow-up was conducted during a five-year period on 672 patients. During the period from one to five years, re-embolization was performed in 11 (1.5%) cases, of which only three occurred during the last 3 years of follow-up. Conclusions: Endovascular embolization is a safe method for the treatment of ruptured intracranial aneurysms, with a low complication rate and good clinical outcome. Higher risk for repeated aneurysm embolization is associated with male sex, alcohol consumption, smoking, hyperlipidemia, aneurysm size, diabetes, aneurysm location, and obliteration rate. This study showed that aneurysms in which recanalization is not observed within 2 years after coil embolization remain stable during a follow-up period of 5 years, except in the case of large aneurysms and low obliteration rates. Full article

Background/Objectives: Some patients with severe hypoxic–ischemic brain injury after out-of-hospital cardiac arrest (OHCA) progress toward brain death, a trajectory not adequately captured by the conventional classification of favorable versus unfavorable neurological outcomes. We developed and internally evaluated a multimodal model combining quantitative brain computed tomography (CT), serum neuron-specific enolase (NSE) at 48 h, and clinical variables to predict operationally defined progression toward brain death (PTBD). Methods: This multicenter retrospective secondary analysis used prospectively collected data from the Korean Hypothermia Network registry. Adult comatose OHCA survivors treated with targeted temperature management between October 2015 and December 2020 were included. Multivariable logistic regression models were developed in the total cohort and in patients with poor neurological outcomes. Model performance was assessed using discrimination, calibration, the Brier score, and bootstrap internal validation. Results: Of 468 patients assessed, 376 were included; their mean age was 58.7 years, and 269 (71.5%) were male. Seventy-four patients (19.7%) met the operational definition of PTBD. In the total cohort, younger age, non-shockable rhythm, low gray-to-white matter ratio (GWR ≤ 1.19), and higher NSE at 48 h were independently associated with PTBD. Among 288 patients with poor neurological outcomes, younger age, low GWR, and higher NSE at 48 h remained independent predictors. The total-cohort model had an AUC of 0.895 and an optimism-corrected AUC of 0.890. Its AUC was higher than that of NSE at 48 h (p < 0.001) but not significantly different from that of GWR alone (p = 0.054). In the poor-outcome subgroup, the model had an AUC of 0.864 and an optimism-corrected AUC of 0.858 and significantly outperformed both GWR (p = 0.012) and NSE at 48 h (p < 0.001). Conclusions: PTBD represents a clinically distinguishable trajectory among patients with poor neurological outcomes after OHCA. A multimodal model using information available within 48 h demonstrated good internally validated performance and may support early risk stratification before definitive neuroprognostication. External validation is required before clinical implementation. Full article

This narrative review critically summarizes the literature on the associations of Type A and Type D personality, together with related personality traits, with cardiovascular disease (CVD) onset, prognosis, cardiac surgery, and rehabilitation outcomes. For the past half a century, there has been a consistent interest in the question of whether or not there is a connection between personality qualities and CVD. At the same time as individuals with a Type A personality who were angry, competitive, and excessively motivated were overrepresented among patients seeking treatment for CVD, it was also noted that these individuals were more likely to acquire coronary artery disease or syndrome. Anger and animosity were among the unfavorable impacts that were found to be connected with worse cardiovascular outcomes, according to the findings of research. After that, a new personality entity was brought into existence, which was referred to as the type D “distressed” personality. This personality type coupled negative affectivity and social inhibition. Type D personality subsequently became a major focus of research, and several studies reported associations with poorer patient-reported health and adverse cardiac outcomes. However, these findings have not been consistently replicated, and the stability, incremental predictive value, and independence of Type D personality from depression, disease severity, and other psychosocial factors remain debated. As a result, there are a number of criticisms that pertain to the current knowledge of the connection between personality construct and the risk of developing cardiovascular diseases as well as the outcome of these diseases. This review provides a critical narrative synthesis of supportive and conflicting evidence and highlights the methodological limitations that currently prevent definitive causal or prognostic conclusions. Full article