Journal of Clinical Medicine

Catheter ablation for atrial fibrillation (AF) is a common treatment strategy in patients with drug-resistant, symptomatic AF. In patients with paroxysmal and short-standing persistent AF, pulmonary vein isolation (PVI) is often enough to prevent recurrence of atrial tachyarrhythmia (ATA). Point-by-point encircling of the PVs with radiofrequency (RF) applications, together with cryoballoon ablation, have been the mainstay strategies for the last 10 to 20 years. Each of these strategies, however, suffers from the delicate balance between preventing PV reconnection, on the one hand (toward more energy), and preventing (mainly esophageal) complications (toward less energy), on the other. The CLOSE protocol was developed as an RF ablation strategy that would result in the safe creation of durable isolation leading to improved outcomes. Basically, the aim of the protocol is to enclose the pulmonary veins with stable, contiguous (intertag distance, ITD ≤  6 mm) and optimized lesions (35 Watts, W, RF applications up to ablation index targets of ≥400 and ≥550 at the posterior and anterior wall). In this review, we describe the background of the CLOSE protocol and the studies from the St Jan Bruges research group on procedural performance, efficacy, and safety of the CLOSE protocol in (a) single-center prospective PILOT study (CLOSE-PILOT), (b) a single-center prospective study with continuous rhythm monitoring (CLOSE to CURE), (c) a database of systematic esophageal endoscopic studies, (d) a multicenter prospective study (VISTAX), and (e) the CLOSE database (comprising > 400 patients). We also discuss the results of the randomized POWER-AF study comparing conventional CLOSE to high power CLOSE (up to 50 W). Finally, we discuss the performance, safety, and efficacy of the CLOSE protocol in light of the emerging changes in the field of catheter ablation being ultra-short high-power ablation and electroporation. Full article

The incidence of pelvic organ prolapse (POP) is increasing in our aging society. We aimed to evaluate the clinical usefulness of translabial ultrasound (TLUS) by comparing the findings of POP-Q examination and TLUS in advanced POP patients and we also aimed to evaluate the prevalence of rectocele and enterocele on the TLUS. We analyzed the TLUS and POP-Q exam findings of 363 symptomatic POP patients who visited our clinic from March 2019 to April 2021. We excluded three patients who had conditions mimicking POP, as revealed by the TLUS. The most common POP type was anterior compartment POP (68.61%), followed by apical compartment (38.61%) and posterior compartment (16.11%) POP. Agreement between the POP-Q exam and TLUS was tested using Cohen’s kappa (κ). p values < 0.05 were considered statistically significant. The incidence of rectocele or enterocele was only 1.67% (6/360) and there was no rectocele or enterocele in most patients (246/252, 96.63%) when the POP-Q exam revealed posterior compartment POP, suggesting that they only had posterior vaginal wall relaxation. The positive predictive value of the POP-Q exam for detecting rectocele or enterocele (as revealed by TLUS) was only 2.38%, whereas the negative predictive value was 100%. In conclusion, the application of TLUS is useful in the diagnosis of POP, especially for differentiation of true POP from conditions mimicking POP. The correlation between the POP-Q exam and TLUS is low, especially in posterior compartment POP, and therefore, patients with POP-Q exam findings suggesting posterior compartment POP should undergo TLUS to check for rectocele or enterocele. The use of TLUS in the diagnosis of POP patients can improve the accuracy of the diagnosis of POP patients in conjunction with a POP-Q exam. Full article

Real-world data report worse 3-month clinical outcomes in elderly patients with acute ischemic stroke (AIS) treated with mechanical thrombectomy (MT). The aim was to identify factors influencing clinical outcome in elderly patients with anterior circulation AIS treated with MT (±intravenous thrombolysis (IVT)). In a retrospective, monocentric study, analysis of prospectively collected data of 138 patients (≥80 years) was performed. IVT was an independent negative predictor (OR 0.356; 95% CI: 0.134–0.942) and female sex an independent positive predictor (OR 4.179, 95% CI: 1.300–13.438) of 3-month good clinical outcome (modified Rankin scale 0–2). Female sex was also an independent negative predictor of 3-month mortality (OR 0.244, 95% CI: 0.100–0.599). Other independent negative predictors of 3-month good clinical outcome were older age, lower pre-stroke self-sufficiency, more severe neurological deficit and longer procedural intervals. Mortality was also independently predicted by longer procedural interval and by the occurrence of symptomatic intracerebral hemorrhage (p < 0.05 in all cases). Our results demonstrated, that in patients aged ≥80 years with anterior circulation AIS undergoing MT (±IVT), IVT reduced the chance of 3-month good clinical outcome and female sex was associated with a greater likelihood of 3-month good clinical outcome and lower probability of 3-month mortality. Full article

Infliximab and vedolizumab are effective treatments for inflammatory bowel disease (IBD), although associated with adverse events (AE). While low or non-existent drug levels and positive antidrug antibodies have been associated with therapeutic failure, there is no clear association between higher drug levels and AE. A cross-sectional study consisting of Crohn’s disease (CD) and ulcerative colitis (UC) patients receiving infliximab or vedolizumab at the Sheba Medical Center was performed. Patients completed a questionnaire regarding AEs related to biological therapy. Serum trough levels obtained on the same day were analyzed. Objective measures of outcomes were retrieved from medical records. Questionnaires were completed by infliximab (n = 169) and vedolizumab (n = 88)-treated therapy patients. Higher infliximab levels were only numerically associated with the occurrence of at least one AE (p = 0.08). When excluding fatigue and abdominal pain, higher infliximab levels were statistically associated with the occurrence of at least one AE (p = 0.03). Vedolizumab drug levels > 18μg/mL were also linked with the occurrence of more AEs. No specific association was observed between the increased levels of either infliximab or vedolizumab and specific AEs (neurological symptoms, upper GI symptoms, infectious complications, and musculoskeletal symptoms). As significant AEs are very rare, additional multi-center studies are required. Full article

As an element of distorted self-image, body image disturbances may be relevant to borderline personality disorder (BPD). Therefore, this systematic review aims to critically discuss and summarize empirical findings in this matter. Based on the available theoretical models, three body image components were identified: (a) perception, (b) affect and cognition, and (c) general body dissatisfaction. We conducted a systematic search of the empirical literature published in English in the MEDLINE, PsycINFO, and Scopus databases until June 2021 using a priori eligibility criteria (BPD; BPD symptoms or features in nonclinical groups; quasipsychotic or psychotic symptoms were not considered). We included k = 10 records meeting the criteria. Compared with other analyzed groups, individuals diagnosed with BPD obtained higher scores in the three components of body image disturbances. The issue of body image in BPD is relatively understudied, although current research findings clearly indicate disturbances in all of the abovementioned body image components in individuals with BPD or significant relationships of these components with BPD traits or symptoms both in clinical and nonclinical samples. Eventually, possible practical implications and future research directions are also discussed. Full article

We aim to investigate the significance of intravesical prostate protrusion (IPP) on the prognosis of non-muscle invasive bladder cancer (NMIBC) after the transurethral resection of bladder tumors (TURBT). For newly diagnosed NMIBC, we retrospectively analyzed the association between prognosis and IPP for at least a 5-year follow-up. A degree of IPP over 5 mm in a preoperative CT scan was classified as severe. The primary endpoint was recurrence-free survival, and the secondary endpoint was progression-free survival. The machine learning (ML) algorithm of a support vector machine was used for predictive model development. Of a total of 122 patients, ultimately, severe IPP was observed in 33 patients (27.0%). IPP correlated positively with age, BPH, recurrence, and prognosis. Severe IPP was significantly higher in the recurrence group and reduced in the recurrence-free survival group (p = 0.038, p =0.032). Severe IPP independently increased the risk of intravesical recurrence by 2.6 times. The addition of IPP to the known oncological risk factors in the prediction model using the ML algorithm improved the predictability of cancer recurrence by approximately 6%, to 0.803. IPP was analyzed as a potential independent risk factor for NMIBC recurrence and progression after TURBT. This anatomical feature of the prostate could affect the recurrence of bladder tumors. Full article

Background: The concern in the scientific community for the study of people with dementia and their families is comprehensible, especially the importance of knowing the effects that caring for the patient has on their family dynamic, paying special attention to the main caregiver. The objective of this study was to analyze the relationship of resilience and emotional intelligence with functional performance in the main caregivers of people with dementia in Spain according to the phase of the disease. Methods: A cross-sectional, descriptive, and analytical study was carried out. A total of 144 primary family caregivers of patients with dementia in Spain were included in the study. The following variables were measured: sociodemographic, psychosocial, and occupational, as well as resilience and emotional intelligence. Results: The caregivers obtained a low moderate resilience (mean = 64.01 ± 14.5), an emotional intelligence bordering between moderate and high (mean = 78.48 ± 14.82), and a 61.8% self-care categorized as somewhat and quite a bit. The presence of higher levels of resilience in family caregivers of people with dementia were positively related to the time spent on self-care (r = 0.227; p = 0.033) and leisure (r = 0.262; p = 0.014), especially in the moderate phase of the disease, while in the severe phase, this relationship appeared with productivity (r = 0.355; p = 0.034). The higher levels of emotional intelligence were positively related to a greater time dedicated to self-care (r = 0.233, p = 0.005), as well as the data observed in the moderate and severe phase (r = 0.214; p = 0.046 and r = 0.398; p = 0.016 respectively). Conclusions: The primary caregivers of relatives with dementia who have higher levels of resilience and emotional intelligence spend more time on self-care and leisure activities, especially in the moderate phase of the disease. Full article

Hand injuries often result in significant functional impairments and are rarely completely restored. The spontaneous regeneration of injured appendages, which occurs in salamanders and newts, for example, has been reported in human fingertips after distal amputation, but this type of regeneration is rare in mammals and is incompletely understood. Here, we study fingertip regeneration by amputating murine digit tips, either distally to initiate regeneration, or proximally, causing fibrosis. Using an unbiased microarray analysis, we found that digit tip regeneration is significantly associated with hair follicle differentiation, Wnt, and sonic hedgehog (SHH) signaling pathways. Viral over-expression and genetic knockouts showed the functional significance of these pathways during regeneration. Using transgenic reporter mice, we demonstrated that, while both canonical Wnt and HH signaling were limited to epidermal tissues, downstream hedgehog signaling (through Gli) occurred in mesenchymal tissues. These findings reveal a mechanism for epidermal/mesenchyme interactions, governed by canonical hedgehog signaling, during digit regeneration. Further research into these pathways could lead to improved therapeutic outcomes after hand injuries in humans. Full article

Objective: To determine the effects of dry needling (DN) in active myofascial trigger points in the teres major muscle compared to an untreated control group in pain during throwing actions, shoulder range of motion (ROM), strength, and extensibility of the tissues in professional handball (HB) athletes. Methods: A randomised, single-blinded, controlled clinical trial was designed. Thirty HB athletes with shoulder pain were randomly assigned to the DN group (n = 15) or control group (n = 15). The DN group received a single session of ultrasound-guided DN technique in the teres major muscle. The control group received no intervention. Pain intensity during throwing actions (Numeric Pain Rating Score), shoulder ROM (inclinometer), isometric strength (hand-held dynamometer), and extensibility (inclinometer) were measured before and after treatment. Results: DN group showed statistically significant improvements with large effect sizes for pain intensity (p < 0.001; E.S: 1.3), internal rotation ROM (p < 0.001; E.S: 3.0) and extensibility (p < 0.001; E.S: 2.9) compared to the control group. No statistically significant differences were found for isometric strength (p > 0.05). Conclusion: A single session of DN in the teres major muscle was effective for improving pain intensity during throwing actions, internal rotation ROM and extensibility in HB athletes with shoulder pain. Full article

There have been significant advancements in male infertility microsurgery over time, and there continues to be significant promise for new and emerging techniques, technologies, and methodologies. In this review, we discuss the history of male infertility and the evolution of microsurgery, the essential role of education and training in male infertility microsurgery, and new technologies in this space. We also review the potentially important role of artificial intelligence (AI) in male infertility and microsurgery. Full article

Objective: Signet-ring cell carcinoma (SRCC) is a rare histopathological subtype of colorectal cancer (CRC) constituting approximately 1% of CRC cases. This study analyzed the incidence and survival rates of colorectal SRCC. Methods: We analyzed the incidence and survival rates of colorectal SRCCs based on patients’ data of the Korea Central Cancer Registry. Results: The age-standardized incidence rates of colon and rectum SRCC in 2017 were 0.17 and 0.07 individuals per 100,000, respectively. Between 1993 and 2017, the 1-, 2-, 3-, 4-, and 5-year relative survival rates of patients with colon SRCC were 65.6%, 49.0%, 38.9%, 34.9%, and 33.0%, respectively, while those of patients with rectum SRCC were 69.6%, 47.8%, 38.5%, 32.8%, and 29.4%, respectively. According to the Surveillance, Epidemiology, and End Results summary stages, the 5-year relative survival rates of colon SRCC between 1993 and 2017 were 70.4% for the localized stage, 41.0% for the regional stage, and 7.0% for the distant stage, while those for rectum SRCC were 60.7%, 34.4, and 3.3%, respectively. Conclusions: Although the incidence of colorectal SRCC is extremely low in South Korea, it has been increasing in recent decades. As the prognosis of colorectal SRCC is extremely poor; clinicians should be aware of the differential diagnosis of SRCC in colorectal cancer cases. Full article

Oral minoxidil is an approved treatment for high blood pressure which is also used as an off-label drug for alopecia. Knowledge about the effects of systemic minoxidil in the paediatric population is limited. A retrospective case series study of paediatric patients with history of systemic minoxidil intake due to contaminated sets of omeprazole was performed to describe side effects of high dose oral minoxidil intake in children. Twenty patients aged between 2 months and 13 years joined the study. They had received high doses of oral minoxidil (mean dose 0.90 mg/kg/day) during a mean time of 38.3 days. Hypertrichosis appeared in 65%, with a mean latency time of 24.31 days. Treatment time was associated with the appearance of hypertrichosis (p < 0.05). Most common initial zone of hypertrichosis was the face. Systemic effects developed in 15%, with no cases of severe disorders. The present study shows a novel insight into the side effects of high doses of oral minoxidil in children. Full article

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease has been described to possibly be associated with ocular surface disturbances. However, whether the virus could invade ocular tissues still remains elusive. In the present study, we tried to investigate the post-mortem presence of SARS-CoV-2 RNA in corneal epithelium gathered by patients with an ante-mortem confirmed diagnosis of Coronavirus disease-19 (COVID-19). Cadavers with an ante-mortem confirmed diagnosis of moderate to severe COVID-19 were examined. Clinical and demographic features were retrieved from hospital patients’ notes. For each cadaver, corneal scrapings, conjunctival swabs (CS) and nasopharyngeal swabs (NPS) were collected to perform real-time reverse transcriptase polymerase chain reaction ((RT)-PCR) for SARS-CoV-2. Fourteen consecutive cadavers with an ante-mortem confirmed diagnosis of moderate to severe COVID-19 were examined. The last NPS performed ante-mortem confirmed SARS-CoV-2 infection in 12/14 (85.7%) patients. The mean death-to-swab time (DtS) was 3.15 ± 0.5 (2.10–5.1) h. The post-mortem NPS and CS found positive for SARS-CoV-2 RNA were 9/14 (64.3%) and 3/28 (10.7%), respectively. None of the corneal epithelium scrapes tested positive to RT-PCR for SARS-CoV-2 RNA. These data promote the SARS-CoV-2 as not able to contaminate the post-mortem corneal epithelium, while it can persist in different other structures of the ocular surface (i.e., the conjunctiva). It is reasonable to assume that such a contamination can occur ante-mortem too. Full article

Previous studies have suggested that varying attention demands in dichotic listening (DL) tasks might be a clinically feasible method to distinguish ‘bottom-up’ from ‘top-down’ deficits in listening. This study aims to investigate DL processing in adults with listening difficulties (LD). We assessed the performance of a listening difficulties group (LDG) (n = 24, mean age = 24, backward digit span = 4.0) and a control group (CG) (n = 25, mean age = 29.2, backward digit span = 6.4) in DL tests involving non-forced and both right and left-forced attention. The results indicated an overall significantly worse performance of LDG compared to the CG, which was greater for forced-left condition. This same result was observed when controlling for working memory (WM) variance. Both groups presented an overall right ear advantage with no difference in terms of the magnitude of advantage. These results indicate that LD presented by the LDG might be due to a combination of sensory and cognitive deficits, with emphasis on the cognitive component. However, the WM, although impaired in the LDG group, was not the main factor in segregating both groups. The role of the additional cognitive processes such as inhibitory control in LD is discussed. Full article

Increased investment in perinatal health in developing countries has improved the survival of preterm newborns, but their significant multiorgan immaturity is associated with short and long-term adverse consequences. Cathepsin B, as a protease with angiogenic properties, may be related to the process of nephrogenesis. A total of 88 neonates (60 premature children, 28 healthy term children) were included in this prospective study. We collected urine samples on the first or second day of life. In order to determine the concentration of cathepsin B in the urine, the commercially available enzyme immunoassay was used. The urinary concentrations of cathepsin B normalized with the urinary concentrations of creatinine (cathepsin B/Cr.) in newborns born at 30–34, 35–36, and 37–41 (the control group) weeks of pregnancy were (median, Q1–Q3) 4.00 (2.82–5.12), 3.07 (1.95–3.90), and 2.51 (2.00–3.48) ng/mg Cr, respectively. Statistically significant differences were found between the group of newborns born at 30–34 weeks of pregnancy and the control group (p < 0.01), and between early and late preterm babies (PTB) (p < 0.05). The group of children born at 35–36 weeks of pregnancy and the control group did not differ significantly. This result suggests that the elevated urinary cathepsin B/Cr. level may be the result of the kidneys’ immaturity in preterm newborns. Full article

Background: We aimed to study the bilateral choroidal thickness (CT) symmetry and difference in uncomplicated pachychoroid subjects using wide-field swept-source optical coherence tomography (SS-OCT). Methods: All subjects underwent a wide-field 16-mm one-line scan using SS-OCT. Bilateral CT was measured at, and compared among, the following 12 points: three points at 900-µm intervals from the nasal optic disc margin (nasal peripapillary area), one point at the subfovea, six points at 900-µm intervals from the fovea to the nasal and temporal areas (macular area), and two peripheral points 5400 and 8100 µm from the fovea (peripheral area). Results: There were no statistically significant differences in CT between the right and left eyes in any area (all p > 0.05); they all showed significant positive correlations (all p < 0.01). However, the correlation coefficients (ρ) were smaller for the nasal peripapillary and peripheral areas compared to the macular area. Conclusions: The CTs in each region were bilaterally symmetrical in subjects with uncomplicated pachychoroid. However, interocular difference in CT increased from the center to the periphery, indicating that the anatomical variation of the nasal peripapillary and peripheral choroid was greater than that of the macula. Full article

Transcatheter tricuspid valve repair (TTVr) has emerged as an alternative for the treatment of severe tricuspid regurgitation (TR). We report our initial experience with an edge-to-edge TTVr system in a high-volume institution. Methods: We included consecutive patients who underwent edge-to-edge TTVr systems. The primary efficacy endpoint was a reduction in the TR of at least one grade. The primary safety endpoint was procedure-related clinical serious adverse events. Results: A total of 28 patients underwent TTVr with edge-to-edge systems. All patients presented with at least severe TR with a high impact on quality of life (82% of patients in NYHA class ≥ III). The Triclip system was the most used device (89%). The primary efficacy endpoint was met in all patients. Only one patient experienced a procedural complication (femoral pseudoaneurysm). At three-month follow-up, 83% of patients were in NYHA I or II (18% baseline vs. 83% 3 months follow-up; p < 0.001). Echocardiography follow-up showed residual TR ≤ 2 in 79% of patients (paired p < 0.001). At the maximum follow-up (median follow up = 372 days), no patients had died. Conclusions: Edge-to-edge TTVr systems seem to represent a very valid alternative to prevent morbidity and mortality associated with TR as depicted by the favorable efficacy and safety. Full article

(1) Background: Clinical presentation, disease distribution, or treatment received may provide insights into the reasons contributing to sex differences in chronic thromboembolic pulmonary hypertension (CTEPH). (2) Methods: We evaluated 453 patients (56% women) between 2007–2019. Data was collected from REHAP (Registro Español de Hipertensión Arterial Pulmonar) registry. Two time periods were selected to evaluate the influence of new treatments over time. (3) Results: Women were older. Baseline functional class was worse, and distance walked shorter in women compared with men. Women had higher pulmonary vascular resistances. Despite this, pulmonary endarterectomy (PEA) was carried out in more men, and women received more frequently pulmonary vasodilators exclusively. The 2014–2019 interval was associated with a better survival only among women. Interestingly, women had a more distal disease during this second period of time. (4) Conclusions: Even though women were older, and received invasive treatments less frequently, mortality was similar in both sexes. The introduction of balloon pulmonary angioplasty and the improvement of pulmonary endarterectomy, especially during the last years, could be associated with a survival benefit among women. Full article

Anemia, iron deficiency and other hematinic deficiencies are a major cause of perioperative transfusion needs and are associated with increased morbidity and mortality. Anemia can be caused either by decreased production of hemoglobin or red blood cells or by increased consumption and blood loss. Decreased production can involve anything from erythropoietin or vitamin B12 insufficiency to absolute or functional lack of iron. Thus, to achieve the goal of patient blood management, anemia must be addressed by addressing its causes. The traditional parameters to diagnose anemia, despite offering elaborate options, are not ideally suited to giving a simple overview of the causes of anemia, e.g., iron status for erythropoiesis, especially during the acute phase of inflammation, acute blood loss or iron deficiency. Reticulocyte hemoglobin can thus help to uncover the cause of the anemia and to identify the main factors inhibiting erythropoiesis. Regardless of the cause of anemia, reticulocyte hemoglobin can also quickly track the success of therapy and, together with the regular full blood count it is measured alongside, help in clearing the patient for surgery. Full article