Background: Abdominal minimally invasive surgery has become increasingly prominent for the treatment of prolapse. Abdominal sacral colpopexy (ASC) is the gold standard for the treatment of advanced apical prolapse; however, alternative surgical approaches such as the abdominal lateral suspension (ALS) have been developed to improve patient outcomes. This study aims to determine whether ALS improves outcomes compared to ASC in multicompartmental prolapse patients. Methods: A prospective, open-label, multicenter, non-inferiority trial was conducted in 360 patients who underwent ASC or ALS for the treatment of apical prolapse. The primary outcome was anatomical and symptomatic cure of the apical compartment at 1-year follow-up; secondary outcomes included prolapse recurrence, re-operation rate, and post-operative complications. A 300-patient cohort was subdivided into 200-patients who underwent ALS and 100-patients who underwent ASC. The confidence interval method was used to calculate the p-value of non-inferiority. Results: At the 12-months follow-up, the objective cure rate of the apical defect was 92% for ALS and 94% for ASC (recurrence rates were 8% and 6%, respectively, and the p-value for non-inferiority was <0.01). The mMesh complication rates were 1% and 2% for ALS and ASC, respectively. Conclusions: This study demonstrated that the ALS technique is not inferior to the gold standard ASC for the surgical treatment of apical prolapse. Full article

Background: Atrial fibrillation (AF) has been described as a common cardiovascular manifestation in patients suffering from coronavirus disease 2019 (COVID-19) and has been suggested to be a potential risk factor for a poor clinical outcome. Methods: In this observational study, all patients hospitalized due to COVID-19 in 2020 in the Cantonal Hospital of Baden were included. We assessed clinical characteristics, in-hospital outcomes as well as long-term outcomes with a mean follow-up time of 278 (±90) days. Results: Amongst 646 patients diagnosed with COVID-19 (59% male, median age: 70 (IQR: 59–80)) in 2020, a total of 177 (27.4%) patients were transferred to the intermediate/intensive care unit (IMC/ICU), and 76 (11.8%) were invasively ventilated during their hospitalization. Ninety patients (13.9%) died. A total of 116 patients (18%) showed AF on admission of which 34 (29%) had new-onset AF. Patients with COVID-19 and newly diagnosed AF were more likely to require invasive ventilation (OR: 3.5; p = 0.01) but did not encounter an increased in-hospital mortality. Moreover, AF neither increased long-term mortality nor the number of rehospitalizations during follow-up after adjusting for confounders. Conclusions: In patients suffering from COVID-19, the new-onset of AF on admission was associated with an increased risk of invasive ventilation and transfer to the IMC/ICU but did not affect in-hospital or long-term mortality. Full article

Identifying factors predisposing individuals to post-acute sequelae of COVID-19 (PASC) would allow for the timely treatment of those vulnerable. Attention on the role of sex and age is growing, but published studies have shown mixed results. Our objective was to estimate the effect modification of age on sex as a risk factor for PASC. We analyzed data from two longitudinal prospective cohort studies on adult and pediatric subjects positive to SARS-CoV-2 infection that were enrolled between May 2021 and September 2022. Age classes (≤5, 6–11, 12–50, >50 years) were based on the potential role of sex hormones on inflammatory/immune and autoimmune processes. A total of 452 adults and 925 children were analyzed: 46% were female and 42% were adults. After a median follow-up of 7.8 months (IQR: 5.0 to 9.0), 62% of children and 85% of adults reported at least one symptom. Sex and age alone were not significantly associated to PASC, but their interaction was statistically significant (p-value = 0.024): the risk was higher for males aged 0–5 (females vs. males HR: 0.64, 95% CI: 0.45–0.91, p = 0.012) and for females aged 12–50 (HR: 1.39, 95% CI: 1.04–1.86, p = 0.025), especially those in the cardiovascular, neurological, gastrointestinal and sleep categories. Further research on PASC with regard to sex and age is warranted. Full article

We compared the changes in cerebral oxygen saturation (ScO₂) levels during cardiac arrest (CA) events using porcine models of ventricular fibrillation CA (VF-CA) and asphyxial CA (A-CA). Twenty female pigs were randomly divided into VF-CA and A-CA groups. We initiated cardiopulmonary resuscitation (CPR) 4 min after CA and measured the cerebral tissue oxygenation index (TOI) using near-infrared spectroscopy (NIRS) before, during, and after CPR. In both groups, the TOI was the lowest at 3–4 min after pre-CPR phase initiation (VF-CA group: 3.4 min [2.8–3.9]; A-CA group: 3.2 min [2.9–4.6]; p = 0.386). The increase in TOI differed between the groups in the CPR phase (p < 0.001); it increased more rapidly in the VF-CA group (16.6 [5.5–32.6] vs. 1.1 [0.6–3.3] %/min; p < 0.001). Seven pigs surviving for 60 min after the return of spontaneous circulation in the VF-CA group recovered limb movement, whereas only one in the A-CA group (p = 0.023) achieved movement recovery. The increase in the TOI did not differ significantly between the groups in the post-CPR phase (p = 0.341). Therefore, it is better to monitor ScO₂ concomitantly with CPR initiation using NIRS to assess the responsiveness to CPR in clinical settings. Full article

Current research on cardiovascular prevention predominantly focuses on risk-stratification and management of patients with coronary artery disease (CAD) to optimize their prognosis. Several basic, translational and clinical research efforts aim to determine the etiological mechanisms underlying CAD pathogenesis and to identify lifestyle-dependent metabolic risk factors or genetic and epigenetic parameters responsible for CAD occurrence and/or progression. A log-linear association between the absolute exposure of LDL cholesterol (LDL-C) and the risk of atherosclerotic cardio-vascular disease (ASCVD) was well documented over the year. LDL-C was identified as the principal enemy to fight against, and soluble proprotein convertase subtilisin kexin type 9 (PCSK9) was attributed the role of a powerful regulator of blood LDL-C levels. The two currently available antibodies (alirocumab and evolocumab) against PCSK9 are fully human engineered IgG that bind to soluble PCSK9 and avoid its interaction with the LDLR. As documented by modern and dedicated “game-changer” trials, antibodies against soluble PCSK9 reduce LDL-C levels by at least 60 percent when used alone and up to 85 percent when used in combination with high-intensity statins and/or other hypolipidemic therapies, including ezetimibe. Their clinical indications are well established, but new areas of use are advocated. Several clues suggest that regulation of PCSK9 represents a cornerstone of cardiovascular prevention, partly because of some pleiotropic effects attributed to these newly developed drugs. New mechanisms of PCSK9 regulation are being explored, and further efforts need to be put in place to reach patients with these new therapies. The aim of this manuscript is to perform a narrative review of the literature on soluble PCSK9 inhibitor drugs, with a focus on their indications and clinical impact. Full article

Upper gastrointestinal bleeding (UGB) in children is a potentially life-threatening condition that represents a challenge for pediatricians and pediatric surgeons. It is defined as bleeding from any location within the upper esophagus to the ligament of Treitz. UGB can have many causes that vary with age. The impact on the child is often proportional to the amount of blood lost. This can range from mild bleeding that is unlikely to cause hemodynamic instability, to massive bleeding that requires admission to the intensive care unit. Proper and prompt management are very important factors in reducing morbidity and mortality. This article aims to summarize current research regarding the diagnosis and treatment of UGB. Most of the data used in the literature published on this subject is extrapolated from adulthood. Full article

Background: This study aimed to evaluate the electrical activity of the rectus femoris, tibialis anterior, and lateral gastrocnemius muscles during the sit-to-stand task and functional mobility after a neurofunctional physiotherapy protocol associated with PBM. Methods: Twenty-five children were randomly allocated to either Active PBM + physiotherapy (n = 13) or PBM sham + physiotherapy (n = 12). PBM was carried out with a LED device (850 nm, 25 J, 50 s per point and 200 mW) at four points over the area with absence of a spiny process. Both groups completed a twelve-week supervised program with two weekly 45–60 min sessions. Pre-training and post-training assessments involved the Pediatric Evaluation of Disability Inventory (PEDI). Muscle activity was assessed using portable electromyography (BTS Engineering) and the electrodes were positioned on the lateral gastrocnemius, anterior tibialis, and rectus femoris muscles. The RMS data were recorded and analyzed. Results: After 24 sessions of the treatment protocol, improvements were found in the PEDI score. The participants presented greater independence in performing the tasks, requiring less assistance from their caregivers. More significant electrical activity was found in the three muscles evaluated between the rest period and execution of the sit-to-stand tasks, both in the more compromised or less compromised lower limbs. Conclusion: Neurofunctional physiotherapy with or without PBM improved functional mobility and electrical muscle activity in children with myelomeningocele. Full article

The definitive diagnosis of Cushing’s disease (CD) in the presence of pituitary microadenoma remains a continuous challenge. Novel available pituitary imaging techniques are emerging. This study aimed to provide a structured analysis of the diagnostic accuracy as well as the clinical use of molecular imaging in patients with ACTH-dependent Cushing’s syndrome (CS). We also discuss the role of multidisciplinary counseling in decision making. Additionally, we propose a complementary diagnostic algorithm for both de novo and recurrent or persistent CD. A structured literature search was conducted and two illustrative CD cases discussed at our Pituitary Center are presented. A total of 14 CD (n = 201) and 30 ectopic CS (n = 301) articles were included. MRI was negative or inconclusive in a quarter of CD patients. ¹¹C-Met showed higher pituitary adenoma detection than ¹⁸F-FDG PET–CT (87% versus 49%). Up to 100% detection rates were found for ¹⁸F-FET, ⁶⁸Ga-DOTA-TATE, and ⁶⁸Ga-DOTA-CRH, but were based on single studies. The use of molecular imaging modalities in the detection of pituitary microadenoma in ACTH-dependent CS is of added and complementary value, serving as one of the available tools in the diagnostic work-up. In selected CD cases, it seems justified to even refrain from IPSS. Full article

Many patients in geriatric rehabilitation (GR) are physically frail at the time of admission and suffer from malnutrition and sarcopenia, which may worsen rehabilitation outcomes. This study aims to obtain insight into the current nutritional care practices in GR facilities across Europe. Methods: In this cross-sectional study, a questionnaire focused on nutritional care practices in GR was distributed across experts in EUGMS member countries. Data were analyzed by using descriptive statistics. Results: In total, 109 respondents working in 25 European countries participated, and the results showed that not all GR patients were screened and treated for malnutrition, and not all participants used (inter)national guidelines when performing nutritional care. The results also showed variations across European geographical areas related to screening and treatment of malnutrition, sarcopenia, and frailty. Even though the participants underlined the importance of dedicating time to nutritional care, they experienced barriers in its implementation, which were mostly due to a lack of resources. Conclusion: As malnutrition, sarcopenia, and frailty are often present in patients admitted to GR, in addition to being interrelated, it is recommended to develop an integrated approach to screening and treatment of all three clinical problems. Full article

Introduction: Wire-guided cannulation (WGC) during endoscopic retrograde cholangiopancreatography (ERCP) is a selective biliary cannulation technique aimed at improving the successful selective biliary cannulation rate and reducing the rate of post-ERCP pancreatitis (PEP) incidence. This study aimed to evaluate the effectiveness of angled-tip guidewires (AGW) vs. straight-tip guidewires (SGW) for biliary cannulation via WGC by a trainee. Methods: We conducted a prospective, single-center, open-labeled, randomized, and controlled trial. Fifty-seven patients were enrolled in this study and assigned randomly to two groups (Group A to S and Group S to A). In this study, we started selective biliary cannulation via WGC with an AGW or an SGW for 7 min. If cannulation was unsuccessful, the other guidewire was used, and cannulation was continued for another 7 min (cross-over method). Results: The selective biliary cannulation success rate over 14 min was significantly higher with an AGW compared with an SGW over 14 min (57.8% vs. 34.3%, p = 0.04) and for the second 7-min segment (36.4% vs. 0%, p = 0.04). No significant difference was found for adverse events such as pancreatitis between the two guidewires. Conclusions: Our results suggest that an AGW is recommended for WGC performed by a trainee. Full article

Background: Invasive lobular carcinoma accounts for 10 to 15% of all breast cancers. The first objective of this retrospective study was to assess the diagnostic performance of FDG-PET/CT scanning in women previously treated for invasive lobular carcinoma with suspected first recurrence. The secondary objectives were to evaluate the impact of PET/CT in a change in treatment and its prognostic value on specific survival. Methods: Patients in whom a PET/CT scan was performed from January 2011 to July 2019 in our Cancer Research Center were enrolled. Recurrence was suspected based on clinical symptoms, abnormal findings on conventional imaging, and/or elevated tumor markers. The diagnosis of recurrence was established by the oncologist after integration of all clinical, biological, histological, imaging, and follow-up data. Prognostic factors of recurrence as predicted by PET were determined using univariate logistic regression. KI67, mitotic index, or grade of mitosis were tested. Survival curves were compared using the log-rank test. Sixty-four patients (mean age: 60.3; SD = 12.4 years) were enrolled. The average time from initial diagnosis of the primary tumor to suspicion of recurrence was 5.2 ± 4.1 years. Forty-eight patients (75%) were judged to have recurrence by the oncologist: 7 local and 41 metastatic, with mainly bone (n = 24), lymph node (n = 14) and liver (n = 10) metastases. Results: Sensitivity, specificity, and positive and negative predictive values of PET/CT to predict recurrence were, respectively: 87%, 87%, 95%, and 70%. SUVmax at recurrence sites was generally high (mean: 6.4; SD = 2.9). False negative PET/CT results occurred with local (n = 2), peritoneal (n = 2), meningeal (n = 1), or bladder (n = 1) recurrences. In 40 patients with available histopathological data from suspected sites of recurrence, 30 PET/CT were true positive. In four patients, primary lung (n = 1) or gastric (n = 1) tumors or lymphomas (n = 2) were found. The detection of a recurrence resulted in a change in treatment in 44/48 patients (92%). No association between recurrence predicted by PET and biological biomarkers was found. Median specific survival appears shorter in patients with metastatic recurrence versus patients with local or no recurrence on PET/CT (p = 0.067). Conclusions: FDG-PET/CT is an effective and reliable tool for the detection of invasive lobular carcinoma recurrence, although certain recurrence sites specific to this histological type can impair its diagnostic performance. Full article

Objective: At the tissue level, disruption of the extracellular matrix network leads to irreversible cardiac fibrosis, which contributes to myocardial dysfunction. At the myocyte level, downregulation of beta-adrenoceptors (beta-AR) reduces adaptation to increased workload. The aim of our study was to analyse the correlation between myocardial fibrosis and beta-AR sensitivity in patients with aortic valve (AV) disease. Methods: A total of 92 consecutive patients who underwent elective AV surgery between 2017–2019 were included in our study (51 with aortic regurgitation (AR-group); 41 with aortic stenosis (AS-group) and left ventricular (LV) biopsies were obtained intraoperatively. In vitro force contractility testing was performed by measuring beta-AR sensitivity (−log EC₅₀[ISO]). In parallel, a quantitative analysis of myocardial fibrosis burden was performed. Results: Mean age at the time of AV surgery was not statistically different in both groups (AR: 53.3 ± 15.3 years vs. AS: 58.7 ± 17.0 years; p = 0.116). The LV end-diastolic diameter was significantly enlarged in the AR-group when compared to the AS-group (59.4 ± 15.6 vs. 39.7 ± 21.2; p < 0.001). Analysis of beta-AR sensitivity (AR: −6.769 vs. AS: −6.659; p = 0.316) and myocardial fibrosis (AR: 8.9% vs. AS: 11.3%; p = 0.284) showed no significant differences between patients with AS and AR. There was no correlation between myocardial fibrosis and beta-AR sensitivity in the whole study cohort (R = 0.1987; p = 0.100) or in the AS-subgroup (R = 0.009; p = 0.960). However, significant correlation of fibrosis and beta-AR sensitivity was seen in AR-patients (R = 0.363; p = 0.023). Conclusion: More severe myocardial fibrosis was associated with reduced beta-AR sensitivity in patients presenting with AR but not with AS. Therefore, our results suggest that in patients with AR, cellular myocardial dysfunction is present and correlates with the extent of myocardial fibrosis in the myocardium. Full article

Background. In the years 2020 and 2021, the COVID-19 pandemic disrupted Poland’s health care system and caused a high number of excess deaths. After nearly 30 years of continuous dynamic increase in the life expectancy of the Polish population and a decrease in premature mortality that led to a reduction in the health gap between Poland and Western European countries, regrettably, a decline in life expectancy was recorded. For males, the decline amounted to 2.3 years and, for females, to 2.1 years. Aim. The aim of this study was to assess changes in the level of premature mortality due to selected cardiovascular diseases in Poland before and during the COVID-19 pandemic. Method. Time trends of deaths of patients under the age of 65 due to ischemic heart disease, cerebrovascular disease and aortic aneurysm were analyzed by gender and age groups. The joinpoint model was used in determining time trends. Results. Premature mortality due to all of the cardiovascular diseases analyzed had been declining steadily by about 5% per year since 2008. However, at the end of the second decade of the 21st century, a significant change in the dynamics of the trend was observed, particularly with regard to deaths from ischemic heart disease, which since 2018 caused premature mortality increases of 10% per year in the female population. In the male population, an increase of nearly 20% per year has been observed since 2019. The changes also affected premature mortality due to cerebrovascular disease. Conclusions. After nearly three decades of significant decline in premature mortality from cardiovascular diseases in Poland, there was a reversal in the trend, in particular as regards ischemic heart disease. The unfavorable changes intensified in the subsequent two years. The simultaneous increase in the number of cardiovascular incidents ending in death and the decline in access to prompt diagnosis and effective treatment may explain the unfavorable changes in the deaths caused by cardiovascular disease and the increase in premature mortality due to cardiovascular disease. Full article

Polycystic ovary syndrome (PCOS) constitutes the most common endocrine disorder in women of reproductive age. Patients usually suffer from severe menstrual irregularities, skin conditions, and insulin resistance-associated health conditions. Peroxisome proliferator-activated receptors (PPARs) are nuclear receptor proteins that regulate gene expression. In order to investigate the role of PPARs in the pathophysiology of PCOS, we conducted a literature review using the MEDLINE and LIVIVO databases and were able to identify 74 relevant studies published between 2003 and 2023. Different study groups reached contradictory conclusions in terms of PPAR expression in PCOS. Interestingly, numerous natural agents were found to represent a novel, potent anti-PCOS treatment alternatives. In conclusion, PPARs seem to play a significant role in PCOS. Full article