The Role of HE4 in Ovarian Cancer Follow-up: A Review.

Objective: The aim of this review was to analyze the state of the art about HE4 and follow-up in patients treated for ovarian cancer. Methods: A literature search was conducted in the MEDLINE database using the key words "HE4" and "ovarian cancer" and "recurrence" or "relapse" or "follow up." Results: Seven of 28 clinical studies were selected. Four studies were prospective, and all of them were based on a small number of patients (8Y73 women). A failure of HE4 levels to normalize at completion of standard therapy may indicate a poor prognosis, thus suggesting the need of a closer follow-up. Moreover, HE4 showed better sensibility and specificity in the diagnosis of ovarian cancer recurrence with respect to CA-125, being also an earlier indicator of the relapse with a lead time of 5 to 8 months. HE4 showed a better performance in this setting if performed in association with other markers (CA-125, CA-72.4). HE4 seems to be an independent predictive factor for the surgical outcome at secondary cytoreductive surgery and to maintain its prognostic role even after the recurrence. Conclusions: These preliminary data start to suggest a superiority of HE4 over CA-125 in the detection of ovarian cancer recurrence. Moreover, the prognostic role of HE4 could help clinicians to personalize the follow-up program, whereas its predictive role could be useful to plan the treatment of the relapse. The role of HE4 in ovarian cancer follow-up deserves to be further investigated in prospective randomized multicentric studies

Global disparities in surgeons’ workloads, academic engagement and rest periods: the on-calL shIft fOr geNEral SurgeonS (LIONESS) study

: The workload of general surgeons is multifaceted, encompassing not only surgical procedures but also a myriad of other responsibilities. From April to May 2023, we conducted a CHERRIES-compliant internet-based survey analyzing clinical practice, academic engagement, and post-on-call rest. The questionnaire featured six sections with 35 questions. Statistical analysis used Chi-square tests, ANOVA, and logistic regression (SPSS® v. 28). The survey received a total of 1.046 responses (65.4%). Over 78.0% of responders came from Europe, 65.1% came from a general surgery unit; 92.8% of European and 87.5% of North American respondents were involved in research, compared to 71.7% in Africa. Europe led in publishing research studies (6.6 ± 8.6 yearly). Teaching involvement was high in North America (100%) and Africa (91.7%). Surgeons reported an average of 6.7 ± 4.9 on-call shifts per month, with European and North American surgeons experiencing 6.5 ± 4.9 and 7.8 ± 4.1 on-calls monthly, respectively. African surgeons had the highest on-call frequency (8.7 ± 6.1). Post-on-call, only 35.1% of respondents received a day off. Europeans were most likely (40%) to have a day off, while African surgeons were least likely (6.7%). On the adjusted multivariable analysis HDI (Human Development Index) (aOR 1.993) hospital capacity > 400 beds (aOR 2.423), working in a specialty surgery unit (aOR 2.087), and making the on-call in-house (aOR 5.446), significantly predicted the likelihood of having a day off after an on-call shift. Our study revealed critical insights into the disparities in workload, access to research, and professional opportunities for surgeons across different continents, underscored by the HDI

Infected pancreatic necrosis: outcomes and clinical predictors of mortality. A post hoc analysis of the MANCTRA-1 international study

: The identification of high-risk patients in the early stages of infected pancreatic necrosis (IPN) is critical, because it could help the clinicians to adopt more effective management strategies. We conducted a post hoc analysis of the MANCTRA-1 international study to assess the association between clinical risk factors and mortality among adult patients with IPN. Univariable and multivariable logistic regression models were used to identify prognostic factors of mortality. We identified 247 consecutive patients with IPN hospitalised between January 2019 and December 2020. History of uncontrolled arterial hypertension (p = 0.032; 95% CI 1.135-15.882; aOR 4.245), qSOFA (p = 0.005; 95% CI 1.359-5.879; aOR 2.828), renal failure (p = 0.022; 95% CI 1.138-5.442; aOR 2.489), and haemodynamic failure (p = 0.018; 95% CI 1.184-5.978; aOR 2.661), were identified as independent predictors of mortality in IPN patients. Cholangitis (p = 0.003; 95% CI 1.598-9.930; aOR 3.983), abdominal compartment syndrome (p = 0.032; 95% CI 1.090-6.967; aOR 2.735), and gastrointestinal/intra-abdominal bleeding (p = 0.009; 95% CI 1.286-5.712; aOR 2.710) were independently associated with the risk of mortality. Upfront open surgical necrosectomy was strongly associated with the risk of mortality (p < 0.001; 95% CI 1.912-7.442; aOR 3.772), whereas endoscopic drainage of pancreatic necrosis (p = 0.018; 95% CI 0.138-0.834; aOR 0.339) and enteral nutrition (p = 0.003; 95% CI 0.143-0.716; aOR 0.320) were found as protective factors. Organ failure, acute cholangitis, and upfront open surgical necrosectomy were the most significant predictors of mortality. Our study confirmed that, even in a subgroup of particularly ill patients such as those with IPN, upfront open surgery should be avoided as much as possible. Study protocol registered in ClinicalTrials.Gov (I.D. Number NCT04747990)

Clinical features and outcomes of elderly hospitalised patients with chronic obstructive pulmonary disease, heart failure or both

Background and objective: Chronic obstructive pulmonary disease (COPD) and heart failure (HF) mutually increase the risk of being present in the same patient, especially if older. Whether or not this coexistence may be associated with a worse prognosis is debated. Therefore, employing data derived from the REPOSI register, we evaluated the clinical features and outcomes in a population of elderly patients admitted to internal medicine wards and having COPD, HF or COPD + HF. Methods: We measured socio-demographic and anthropometric characteristics, severity and prevalence of comorbidities, clinical and laboratory features during hospitalization, mood disorders, functional independence, drug prescriptions and discharge destination. The primary study outcome was the risk of death. Results: We considered 2,343 elderly hospitalized patients (median age 81 years), of whom 1,154 (49%) had COPD, 813 (35%) HF, and 376 (16%) COPD + HF. Patients with COPD + HF had different characteristics than those with COPD or HF, such as a higher prevalence of previous hospitalizations, comorbidities (especially chronic kidney disease), higher respiratory rate at admission and number of prescribed drugs. Patients with COPD + HF (hazard ratio HR 1.74, 95% confidence intervals CI 1.16-2.61) and patients with dementia (HR 1.75, 95% CI 1.06-2.90) had a higher risk of death at one year. The Kaplan-Meier curves showed a higher mortality risk in the group of patients with COPD + HF for all causes (p = 0.010), respiratory causes (p = 0.006), cardiovascular causes (p = 0.046) and respiratory plus cardiovascular causes (p = 0.009). Conclusion: In this real-life cohort of hospitalized elderly patients, the coexistence of COPD and HF significantly worsened prognosis at one year. This finding may help to better define the care needs of this population

Deep brain stimulation effects on lower urinary tract function: Systematic review and meta-analysis

INTRODUCTION: While efficacy of deep brain stimulation for motor symptoms of neurological disorders is well accepted, its effects on the autonomic system remain controversial. We aimed to systematically assess all available evidence of deep brain stimulation effects on lower urinary tract function. METHODS: This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Studies were identified by electronic search of Cochrane Central Register of Controlled Trials, Embase, Medline, Scopus, and Web of Science (last search July 12, 2019) and by screening of reference lists and reviews. RESULTS: After screening 577 articles, we included 29 studies enrolling a total of 1293 patients. Deep brain stimulation of the globus pallidus internus (GPi), pedunculopontine nucleus (PPN), and subthalamic nucleus (STN) had an inhibitory effect on detrusor function, while deep brain stimulation of the ventral intermediate nucleus of the thalamus (VIM) showed an excitatory effect. In the meta-analysis, deep brain stimulation of the STN led to a significant increase in maximum bladder capacity (mean difference 124 mL, 95% confidence interval 60-187 mL, p = 0.0001) but had no clinically relevant effects on other urodynamic parameters. Adverse events (reported in thirteen studies) were most commonly respiratory issues, postural instability, and dysphagia. Risk of bias and confounding was relatively low. CONCLUSIONS: Deep brain stimulation does not impair lower urinary tract function and might even have beneficial effects. This needs to be considered in the deep brain stimulation decision-making process helping to encourage and to reassure prospective patients

Oxidative stress-related factors in Bartter's and Gitelman's syndromes: relevance for angiotensin II signalling

IF: 2,57

Rho kinase and PAI-1 in Bartter/Gitelman syndromes. Relationship to angiotensin II signaling

OBJECTIVE: Angiotensin II (Ang II)-mediated activation of Rho kinase (ROK) is involved in the pathophysiology of hypertension and cardiovascular remodeling. ROK also controls plasminogen activator inhibitor-1 (PAI-1) which promotes vascular fibrosis contributing to atherogenesis. Bartter's and Gitelman's syndromes (BS/GS) are useful models to investigate abnormalities of vascular tone regulation, due to their reduced short- and long-term signaling pathways of Ang II. This study evaluated, using BS/GS as a model, ROK and PAI-1 gene and protein expression and the effect of Ang II co-incubation on ROK and PAI-1 gene and protein expression. DESIGN, METHODS AND RESULTS: We measured ROK and PAI-1 gene and protein expression [reverse transcription-polymerase chain reaction (RT-PCR) and Western blot] in mononuclear cells (PBM) from one BS and eight GS patients. The effect of Ang II on ROK and PAI-1 gene and protein expression was also evaluated and compared with 10 controls. ROK gene and protein expression was reduced in BS/GS [0.47 +/- 0.11 densitometric units (d.u.) versus 0.70 +/- 0.04 d.u., P = 0.0038 and 0.39 +/- 0.07 d.u. versus 0.55 +/- 0.07 d.u., P = 0.0026, respectively]. The basal level of PAI-1 gene and protein expression did not differ (0.40 +/- 0.03 d.u. versus 0.39 +/- 0.02 d.u. and 0.81 +/- 0.02 d.u. versus 0.83 +/- 0.02 d.u., respectively). Ang II increased ROK and PAI-1 gene and protein expression only in controls: from 0.70 +/- 0.04 to 0.90 +/- 0.06 d.u., P = 0.007 (ROK mRNA); from 0.55 +/- 0.07 to 0.86 +/- 0.07 d.u., P = 0.0005 (ROK protein); from 0.40 +/- 0.02 to 0.63 +/- 0.03 d.u., P = 0.001 (PAI-1 mRNA); and from 0.83 +/- 0.02 to 1.34 +/- 0.16 d.u., P = 0.0023 (PAI-1 protein). CONCLUSIONS: This study confirms BS/GS as a human model to investigate interrelated systems involved in the pathophysiology of hypertension and throws more light on the cellular mechanisms of BS/GS reduced Ang II short- and long-term signaling pathways