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Unveiling the impact of perceived stigma on psychological well-being in adult patients with inflammatory bowel disease: The mediating role of patient engagement
No full textThis study elucidated the impact of perceived stigma on the well-being of inflammatory bowel disease (IBD) patients and explored the mediating role of patient engagement. A descriptive cross-sectional study was conducted using an online survey, recruiting participants through the Italian IBD patient organization. The survey assessed perceived stigma, psychological well-being, and patient engagement using validated instruments. Data were analyzed using multiple regressions and bias-corrected bootstrapping analysis. Perceived stigma significantly predicted psychological well-being, and patient engagement significantly predicted well-being. Patient engagement partially mediated the relationship between perceived stigma and well-being, suggesting that lower levels of patient engagement were associated with higher perceived stigma, negatively affecting well-being. Perceived stigma significantly impairs the psychological well-being of IBD patients. However, patient engagement is important for mitigating adverse effects of stigma and enhancing overall well-being. Interventions to reduce stigma and promote patient engagement are essential for improving health outcomes in IBD management
Socio-economic status and the effect of guideline-directed medical therapy in the STRONG-HF study
No full textAims: Acute heart failure (AHF) impacts millions globally, with outcomes varying based on socio-economic status (SES). Methods: SES measured by annual household income, years of education and medical insurance coverage. Each patient's income and education level relative to the median or mean, respectively, in the country was calculated, and categorized into tertiles (0, 1 or 2 from lowest to highest). SES scores (0–5) were computed as the sum of these levels plus insurance coverage (0 = no or 1 = yes). Patients' baseline characteristics, outcomes (HF readmission, death and their composite) and the effect of high-intensity care (HIC) vs. usual care (UC) were examined by SES scores 0–2, 3 and 4–5. Results: Lower SES patients, who were younger, predominantly female, Black and non-European, had fewer comorbidities such as atrial fibrillation, diabetes and ischaemic heart disease and exhibited milder HF, indicated by a lower NYHA class, lower creatinine and higher cholesterol before discharge. Despite having milder HF and less comorbidities, after adjusting for baseline characteristics, patients with higher SES had numerically better outcomes, though differences were not statistically significant. 180-day hazard ratios (HRs) for HF readmission or death were 0.75 (95% CI 0.48–1.16) for SES scores of 3 and 0.85 (95% CI 0.58–1.23) for scores of 4–5, compared to 0–2. Higher SES patients had numerically better treatment effect from HIC, with HRs of 0.69 for SES 0–2, 0.72 for SES 3 and 0.50 for SES 4–5. Conclusions: In this post hoc analysis of the STRONG-HF study, lower SES was associated with milder acute HF but similar 180-day outcomes. Higher SES patients benefitted more from HIC
Genotype and phenotype spectrum of Charcot-Marie-Tooth disease due to mutations in SORD
Get PDFBiallelic loss-of-function mutations in the sorbitol dehydrogenase (SORD) gene cause the most common recessive type of Charcot-Marie-Tooth disease (CMT), CMT-SORD. However, the full genotype-phenotype spectrum and progression of the disease remain to be defined. Notably, a multicentre phase 2/3 study to test the efficacy of govorestat (NCT05397665), a new aldose reductase inhibitor, is currently ongoing. Diagnosing CMT-SORD will become imperative when disease-modifying therapies become available. In this cross-sectional multicentre study, we identified 144 patients from 126 families, including 99 males (69%) and 45 females (31%). Patients represented multiple ancestries, including European, Hispanic, Chinese, Near Eastern and Northern African. We confirmed c.757delG (p.Ala253GlnfsTer27) as the most common pathogenic allele, followed by c.458C>A (p.Ala153Asp), while other variants were identified, mostly in single cases. The average sorbitol level in CMT-SORD patients was significantly higher compared to controls and heterozygous carriers, independently from serum storage duration, sex or variant type. Two-thirds of cases were diagnosed with CMT2 while one-third had distal hereditary motor neuropathy. Disease onset was usually in the second decade of life. Although foot dorsiflexion was the most affected muscle group, dorsal and plantar flexion had a similar degree of weakness in most cases (difference of Medical Research Council score ≤ 1). One-fourth of patients used ankle foot orthoses, usually in their 30s, but most patients maintained independent ambulation later in life. Nerve conduction studies were suggestive of a motor predominant axonal neuropathy, with reduced conduction velocities in the intermediate range in a quarter of the cases. Sensory conductions in the upper limbs appeared more frequently affected than in the lower limbs. Foot dorsiflexion and plantar flexion decreased significantly with age. Male sex was significantly associated with the severity of distal lower limb weakness (plantar flexion) and a larger change over time (dorsiflexion). In conclusion, CMT-SORD is a frequent recessive form of axonal, motor predominant CMT, with prominent foot dorsiflexion and plantar flexion involvement. Fasting serum sorbitol is a reliable biomarker of the condition that can be utilized for pathogenicity assessment of identified rare SORD variants
Mitral regurgitation evolution after transcatheter tricuspid valve interventions - A sub-analysis of the TriValve registry
Get PDFAims: Transcatheter tricuspid valve interventions (TTVI) are increasingly used to treat patients with significant tricuspid regurgitation (TR). The evolution of concurrent mitral regurgitation (MR) severity after TTVI is currently unknown and may be pivotal for clinical decision-making. The aim of this study was to assess the evolution of MR after TTVI and to identify predictors of MR worsening and improvement. Methods and results: This analysis is a substudy of the TriValve Registry, an international registry designed to collect data on TTVI. This substudy included all patients with echocardiographic data on MR evolution and excluded those with a concomitant tricuspid and mitral transcatheter valve intervention or with a history of mitral valve intervention. The co-primary outcomes were MR improvement and worsening at two timepoints: pre-discharge and 2-month follow-up. This analysis included 359 patients with severe TR, mostly (80%) treated with tricuspid transcatheter edge-to-edge repair (T-TEER). MR improvement was found in 106 (29.5%) and 99 (34%) patients, while MR worsening was observed in 34 (9.5%) and 33 (11%) patients at pre-discharge and 2-month follow-up, respectively. Annuloplasty and heterotopic replacement were associated with MR worsening. Independent predictors of MR improvement were: atrial fibrillation, T-TEER, acute procedural success, TR reduction, left ventricular end-diastolic diameter > 60 mm, and beta-blocker therapy. Patients with moderate-to-severe/severe MR following TTVI showed significantly higher death rates. Conclusion: MR degree variation is common after TTVI, with most cases showing improvement. Clinical and procedural characteristics may predict the MR evolution, in particular procedural success and T-TEER play key roles in MR outcomes. TTVI may be beneficial, even in the presence of functional MR
Cardiovascular Risk Predicts White Matter Hyperintensities, Brain Atrophy and Treatment Resistance in Major Depressive Disorder: Role of Genetic Liability
Get PDFIntroduction: Depressive disorders are a leading cause of global disease burden, particularly with the challenge of treatment-resistant depression (TRD). Research points to a complex bidirectional relationship between cardiovascular (CV) risk factors and TRD, with CV risk negatively impacting brain structure and potentially influencing antidepressant resistance. Moreover, the association between depression and the genetic vulnerability to cardiovascular disease suggests a shared pathophysiological process between the two. This study investigates the mediating role of brain structural alterations in the relationship between CV and cerebrovascular (CeV) risk and treatment resistance in depression. Methods: We assessed 165 inpatients with Major depressive disorder. Each patient's CV risk was assessed via the QRISK 3 calculator. For a subset of patients, CV and CeV disease polygenic risk scores (PRS) were obtained. All patients underwent a 3 T MRI scan, and white matter hyperintensities estimates and indicators of brain trophic state were obtained. Results: Both CV risk and CV disease PRSs are associated with treatment resistance status, white matter hyperintensities, and indicators of brain atrophy. Mediation analyses suggested that CV-induced brain alterations might underlie the relation between CV genetic and phenotypic risk and antidepressant treatment resistance. Conclusion: These results underscore the need to explore cardiovascular risk management as part of treatment strategies for depression, pointing toward a shared pathophysiological process linking heart and brain health in treatment-resistant depression
Impact of Anatomical Resection on Non-transplantable Recurrence Among Patients with Hepatocellular Carcinoma: An International Multicenter Inverse Probability of Treatment Weighting Analysis
Get PDFBackground: Among patients with hepatocellular carcinoma (HCC), the impact of anatomic resection (AR) versus non-anatomic resection (NAR) on non-transplantable recurrence (NTR) remains poorly defined. We sought to compare the risk of NTR among patients treated with AR versus NAR as the primary surgical strategy for HCC. Patients and Methods: Patients with HCC within Milan criteria who underwent curative-intent resection between 2000 and 2020 were identified from an international multi-institutional database. The inverse probability of treatment weighting (IPTW) method was utilized to compare short- and long-term outcomes among patients undergoing AR versus NAR. Results: Among 1038 patients, 747 (72.0%) patients underwent AR, while 291 (28.0%) patients underwent NAR. After IPTW adjustment, patients who underwent AR had better 5-year recurrence-free survival than individuals treated with NAR (63.9 vs. 52.0%; hazard ratio [HR] 0.78; 95% confidence interval [CI] 0.62–0.99); however, there was no difference in 5-year overall survival (80.2 vs. 75.6%; HR 0.76; 95% CI 0.55–1.05). Notably, individuals who underwent AR were less likely to have a NTR versus individuals treated with NAR (3-year NTR 9.8 vs. 14.4%; HR 0.62; 95% CI 0.40–0.96). In particular, AR was associated with a lower risk of NTR among patients with a medium tumor burden score (TBS) (HR 0.53; 95% CI 0.28–0.99), while the benefit among patients with a low TBS was less pronounced (HR 0.73; 95% CI 0.40–1.32). Conclusions: AR was associated with a lower risk of NTR and improved recurrence-free survival (RFS) among patients with HCC, especially individuals with higher TBS. An anatomically defined surgical approach should be strongly considered in patients with a higher HCC tumor burden
Cefiderocol therapy among immunocompromised adult patients: a descriptive analysis from a prospective, multicentre cohort study
No full textPurpose The global rise in infections due to multidrug-resistant Gram-negative bacteria (MDRGNB) infections has disproportionately impacted immunocompromised (IC) hosts. Cefiderocol, a novel siderophore cephalosporin, exhibits potent activity against MDRGNB, but limited data exist on its use in IC patients. This study aimed to describe cefiderocol use in IC patients. Methods Patients and therapy characteristics were descriptively reported, and outcomes were compared between IC and non-IC patients. Cox regression models were used to identify factors associated with mortality. Results Among 185 patients, 84 (45.4%) were IC. Similar descriptive rates were observed in IC and non-IC groups regarding indications for cefiderocol use, choice of monotherapy versus combination therapy, or empirical versus targeted treatment. The 28-day clinical cure rates were similar across patients receiving targeted cefiderocol therapy for infection due to Pseudomonas aeruginosa (81%, 17/21), Enterobacterales (77.3%, 17/22) and Acinetobacter baumannii (42%, 21/50). Thirty-day mortality was comparable between IC and non-IC patients (40.8%, 95% confidence interval [CI] 27.9-56.8 vs 33.3%, 95% CI 22.9-46.9; p = 0.5430). In multivariable analysis IC status was not associated with higher mortality. Conclusion Cefiderocol use in IC patients resulted in clinical outcomes comparable to non-IC patients when treating MDRGNB infections. IC status was not associated with an increased mortality, emphasising the importance of effective antimicrobial therapy. Further investigation is needed to clarify the relative impact of the administered treatment vs. the patients' clinical condition in influencing the prognosis of Acinetobacter baumannii infections
Chronobiologic treatments for mood disorders
No full textChronotherapeutics are nonpharmacologic interventions whose development stems from investigations into sleep and circadian rhythm abnormalities associated with mood disorder. These therapies utilize controlled exposure to environmental cues (light, darkness) to regulate biologic rhythms. They encompass sleep–wake manipulations (partial/total sleep deprivation, sleep phase adjustment) and light therapy approaches. Growing evidence supports the safety and efficacy of chronotherapeutics in clinical settings. Indeed, they target core depressive symptoms, including suicidality and may represent a novel therapeutic approach for treatment-resistant depression. This makes them a viable treatment option, both as a monotherapy and in combination with existing psychopharmacologic medications and paves the way for their potential inclusion as first-line treatments for mood disorders
Validation of the Iwate scoring system for the stratification of laparoscopic liver resections: An international multicenter study
No full textIntroduction: The Iwate difficulty scoring system (DSS) is one of the most widely validated DSS for laparoscopic liver resection (LLR). However, these studies only validated the 4 difficulty levels and did not validate the 12-point difficulty index of the system. To address current limitations in the studies validating the Iwate difficulty scoring system (DSS), we performed an international multicenter study to validate the Iwate DSS across both its four difficulty levels and 12-point difficulty index. Methods: A retrospective cohort study of 22,252 patients undergoing LLR across 64 centers worldwide between 2005 and 2021 was performed. Baseline characteristics and perioperative outcomes were analyzed across the four difficulty levels and 12-point difficulty index of the Iwate DSS. Results: A total of 14,759 patients met the inclusion criteria. The main indications for LLR were hepatocellular carcinoma/intrahepatic cholangiocarcinoma (52.8 %), and metastatic tumors liver (26.5 %). In terms of underlying liver pathology, 5127 patients (34.8 %) had liver cirrhosis, and 1214 patients (8.3 %) had portal hypertension. Intraoperative outcomes (operation time, blood loss, blood transfusion, use of Pringles maneuver and open conversion) and postoperative outcomes (length of stay, morbidity, major complications, and 90-day mortality) significantly increased with stepwise increases across the four difficulty levels (P < 0.001) and 12-point difficulty index (P < 0.001). These trends remained significant following adjustment for baseline characteristics (P < 0.001). Conclusion: The Iwate DSS 12-point difficulty index and four difficulty levels correlated well with LLR difficulty as determined by key surrogate perioperative measures
Clinical and biological heterogeneity of Grade 2 digestive neuroendocrine neoplasms: prognostic significance of the 10% Ki-67 index cutoff and implications for treatment strategies. A longitudinal study
No full textBackground: Digestive neuroendocrine neoplasms (NENs) encompass a heterogeneous group of tumors with varying prognoses and clinical behaviors. Grade 2 (G2) tumors, defined by a Ki-67 index between 3% and 20%, are particularly challenging to manage due to their intermediate and variable biological behavior. Evidence suggests a distinct prognosis between G2 digestive NENs with a Ki-67 index < 10% and those with a Ki-67 index ≥ 10%. Aim: To investigate the clinical and biological heterogeneity between Grade 1 (G1) and G2 digestive NENs, and within G2 tumors, with a focus on the prognostic significance of a 10% Ki-67 index cutoff. Methods: This study involved a combined retrospective and prospective analysis of patients with low-grade G1 and G2 digestive NENs managed at IRCCS San Gerardo Hospital in Monza, Italy, between January 2000 and May 2024. Data on patient demographics, tumor characteristics, treatment modalities, and survival outcomes were collected and potential differences were analyzed between G1, G2 with Ki-67 index < 10% and G2 with Ki-67 index ≥ 10%. Results: Out of a total of 113 enrolled patients, 69 (61%) had G1 tumors, and 44 (39%) had G2 tumors. Median tumor size at diagnosis was 19 mm (IQR: 12–25 mm), with primary lesions mainly localized in the pancreas (57% among G1 and 45% among G2). Most G1 tumors were diagnosed at stage I (29 patients, 42%), while the majority of G2 tumors were metastatic at diagnosis (24 patients, 54.5%). Patients with G1 tumors exhibited a slightly higher 5-year OS rate compared to G2 tumors (98.1% vs. 92.8% respectively, though not statistically significant), and a significantly longer median PFS (141 vs. 22 months, p = 0.0003). Within the G2 group, 31 patients (70%) had a Ki-67 index < 10%, while 13 (30%) had a Ki-67 index ≥ 10%, with comparable baseline characteristics. A Ki-67 index < 10% was associated with a significantly better median PFS (38 vs. 8 months for tumors with Ki-67 index ≥ 10% G2 tumors, p = 0.002). PFS after first-line medical therapy was significantly longer in patients with a Ki-67 index < 10%, compared to those with ≥ 10% (undefined vs. 16 months, p = 0.0085), as well as median post-surgical PFS (84 vs. 10.5 months, p < 0.0001). Multivariate analysis identified higher tumor grade, advanced stage at diagnosis, and absence of PRRT as independent predictors of worse outcomes. Conclusions: The findings highlight the significant clinical heterogeneity within G2 digestive NENs. A Ki-67 index cutoff of 10% within G2 tumors may serve as a critical prognostic marker, with patients with a Ki-67 index < 10% exhibiting significantly better outcomes in terms of PFS. These results suggest that the Ki-67 index could play an essential role in guiding treatment strategies, emphasizing the need for personalized approaches in managing G2 digestive NENs