J. Clin. Med., Volume 12, Issue 14 (July-2 2023) – 322 articles

Background: Liver transplantation (LT) is a routine therapeutic approach for patients with acute liver failure, end-stage liver disease and/or early-stage liver cancer. While 5-year survival rates have increased to over 80%, long-term outcomes are critically influenced by extrahepatic sequelae of LT and immunosuppressive therapy, including diabetes mellitus (DM). In this study, we used machine learning (ML) to predict the probability of new-onset DM following LT. Methods: A cohort of 216 LT patients was identified from the Disease Analyzer (DA) database (IQVIA) between 2005 and 2020. Three ML models comprising random forest (RF), logistic regression (LR), and eXtreme Gradient Boosting (XGBoost) were tested as predictors of new-onset DM within 12 months after LT. Results: 18 out of 216 LT patients (8.3%) were diagnosed with DM within 12 months after the index date. The performance of the RF model in predicting the development of DM was the highest (accuracy = 79.5%, AUC 77.5%). It correctly identified 75.0% of the DM patients and 80.0% of the non-DM patients in the testing dataset. In terms of predictive variables, patients’ age, frequency and time of proton pump inhibitor prescription as well as prescriptions of analgesics, immunosuppressants, vitamin D, and two antibiotic drugs (broad spectrum penicillins, fluocinolone) were identified. Conclusions: Pending external validation, our data suggest that ML models can be used to predict the occurrence of new-onset DM following LT. Such tools could help to identify LT patients at risk of unfavorable outcomes and to implement respective clinical strategies of prevention. Full article

We conducted a thorough literature review on the emerging role of failure to rescue (FTR) as a quality metric for cardiovascular surgery and critical care. For this purpose, we identified all original research studies assessing the implementation of FTR in cardiovascular surgery and critical care from 1992 to 2023. All included studies were evaluated for their quality. Although all studies defined FTR as mortality after a surgical complication, a high heterogeneity has been reported among studies regarding the included complications. There are certain factors that affect the FTR, divided into hospital- and patient-related factors. The identification of these factors allowed us to build a stepwise roadmap to reduce the FTR rate. Recently, FTR has further evolved as a metric to assess morbidity instead of mortality, while being also evaluated in the context of interventional cardiology. All these advances are further discussed in the current review, thus providing all the necessary information to surgeons, anesthesiologists, and physicians willing to implement FTR as a metric of quality in their establishment. Full article

The treatment of dentofacial deformities generally includes orthognathic surgery in which mandibular condyle changes following surgery are a common cause of relapse. This study investigated the changes in the mandibular condyle and related muscles to identify the factors that affected the changes in the mandibular condyle after orthognathic surgery in skeletal class II patients. This research studied 60 joints in 30 patients with skeletal class II dentofacial deformities who received surgical orthodontic treatment, including bilateral sagittal split ramus osteotomy, and underwent computed tomography before and after orthodontic treatment. The mandibular condyle, masseter, and medial pterygoid muscles were reconstructed and measured in 3D. Condylar positional and morphology changes, masseter and medial pterygoid muscle volume, temporomandibular joint (TMJ) pain, and distal segment movement were analyzed. The study observed that both the masseter and medial pterygoid muscle volumes decreased with statistical significance. The changes in the horizontal direction were positively correlated with the amount of movement. The findings indicated that mandibular condyle changes were significantly affected by the movement of the distal segment, the medial pterygoid muscle volume, and the direction of the distal segment, which influenced the treatment’s long-term stability after orthognathic surgery. Full article

We investigated the association between mental disorders and the incidence rate of retinal vein occlusion (RVO) in young Korean adults. This nationwide cohort study included subjects aged 20–40 years who underwent the Korean National Health Examination between 2009 and 2012. The diagnoses of RVO and mental disorders were based on the International Classification of Diseases Tenth Revision codes. Multivariate Cox proportional hazard regression models were used to evaluate the objective. In total, 6,891,399 subjects were included at baseline and 6,597,803 subjects (mean age, 30.86 ± 4.99) were finally analyzed for a mean follow-up duration of 7.36 ± 1.13 years, with the mental disorders group followed for 7.27 ± 1.15 years and the non-diagnosed group for 7.37 ± 1.12 years. Among a total of 10,145 subjects diagnosed with RVO, 1304 had been diagnosed with mental disorders, while 8841 had not. Cumulative incidence of RVO demonstrated a substantially higher incidence probability in subjects with mental disorders (log-rank p < 0.0001). Mental disorders were associated with an increased incidence rate of RVO (hazard ratio [HR]: 1.268; 95% confidence interval; [CI]: 1.196–1.344). In the subgroup analysis, subjects with depression, sleep disorder, and anxiety disorder exhibited an increased risk of incidence of RVO in all regression models (all p < 0.001). In conclusion, mental disorders and the incidence rate of RVO were significantly positively correlated in a Korean nationwide population-based cohort study. These findings suggest that mental disorders may also be associated with the pathophysiology of RVO in young adults. Full article

A paradox regarding Alzheimer’s dementia (AD) and mild cognitive impairment (MCI) is thats spontaneous cure of AD has never been reported, whereas spontaneous cure for MCI occurs fequently. This article analyzes what accounts for this difference. It holds that it is not merely because, for any condition, a stage is reached beyond which it cannot be reversed, since even widely metastatic cancer would be curable were there effective chemotherapy and rheumatoid arthritis became controllable when immune-suppressant treatment was introduced; thus, so could AD be reversible via effective therapy. The analysis presented leads to an explanation of the paradox that is in four categories: (1) levels of transforming growth factor-β are significantly reduced after the transition from MCI to AD; (2) levels of Wnt/β-catenin are significantly reduced after the transition; (3) there is altered epidermal-mesenchymal transition (EMT) in neurons after the transition; (4) there may be risk factors that are either newly operative or pre-existing but worsened at the time of transition, that are particular to individual patients. It is suggested that addressing and ameliorating all of those four categories might cure AD. Medications to address and ameliorate each of the four categories are described. Full article

Background: The partial dislocation of the talus from the calcaneus and navicular bones is a primary factor leading to a prolonged overpronation during weightbearing. This study aimed to assess the possibility of returning to physical activity and long-term patient satisfaction after an extra-osseous talotarsal stabilization (EOTTS) procedure with a HyProCure sinus tarsi implant for partial talotarsal joint dislocation (TTJ). Methods: A total of 41 adult patients (61 feet), with an average age of 46.41, were included and treated surgically with EOTTS as a stand-alone surgery. Physical activity and functional scores were assessed pre- and post-operatively using questionnaires—the UCLA Activity Score, Symptom-Related Ankle Activity Scale (SAAS), Sports Frequency Score (SFS), Lower Extremity Functional Scale (LEFS), and VAS scale. Satisfaction was assessed on a ten-point scale. The follow-up period was on average 8.61 years (from 7.33 to 10.31). Results: EOTTS had a positive impact on physical activity, and a high rate of patient satisfaction (8.95 ± 1.9) was noted. The treatment led to a reduction in foot pain, as well as an increase in SAAS and LEFS scores (15,6% and 19,3%, respectively, p < 0.01). The VAS pain score decreased by 18,6% (p < 0.001). SFS and UCLA scores showed a small increase, but it was not statistically significant. A positive correlation was noted between patient satisfaction and time of physical activity per week (R = 0.33, p = 0.04), and also between patient satisfaction and SAAS scores (R = 0.43, p =0.005). Pain from other joints (knee, hip) was eliminated or reduced in 40% of patients after surgery. Conclusions: EOTTS with a HyProCure implant is an effective long-term treatment option for partial talotarsal joint dislocation, leading to a reduction in foot pain and increased patient satisfaction, and allowing for a return to physical activity. Full article

The introduction of gliflozins in the management of type 2 diabetes mellitus leads to a better control of hyperglycemia, obesity, hypertension, dyslipidemia, and fluid retention. Most importantly, it also improves renal survival and reduces major cardiovascular events and mortality. Gliflozins were also found to induce erythropoietin (EPO) synthesis, leading to reticulocytosis and erythropoiesis. The mechanism(s) by which gliflozins induce erythropoiesis is a matter of debate. Although the canonical pathway of triggering EPO synthesis is through renal tissue hypoxia, it has been suggested that improved renal oxygenation may facilitate EPO synthesis via non-canonical routes. The latter proposes that the recovery of peritubular interstitial fibroblasts producing erythropoietin (EPO) is responsible for enhanced erythropoiesis. According to this hypothesis, enhanced glucose/sodium re-uptake by proximal tubules in uncontrolled diabetes generates cortical hypoxia, with injury to these cells. Once transport workload declines with the use of SGLT2i, they recover and regain their capacity to produce EPO. In this short communication, we argue that this hypothesis may be wrong and propose that gliflozins likely induce EPO through the documented intensification of renal hypoxia at the corticomedullary junction, related to the translocation of tubular transport from cortical segments to medullary thick ascending limbs. We propose that gliflozins, through intensified hypoxia in this region, trigger local EPO synthesis in peritubular interstitial cells via the canonical pathway of blocking HIF-prolyl hydroxylases (that initiate HIF alpha degradation), with the consequent stabilization of HIF-2 signal and an apocrinic induction of EPO in these same cells. Full article

Although previous studies investigated the influence of cardiovascular risk (CVR) factors in patients with acute coronary syndrome, data concerning the effect of CVR factors on the prognosis of patients with cardiogenic shock (CS) is scarce. Consecutive patients with CS were prospectively included from 2019 to 2021. The prognosis of patients with “low CVR” (i.e., 0–1 CVR factors) was compared to patients with “high CVR” (i.e., 2–4 CVR factors) according to presence or absence of arterial hypertension, diabetes mellitus, hyperlipidaemia or smoking. The primary endpoint was 30-day all-cause mortality. Statistical analyses included Kaplan-Meier and Cox proportional regression analyses. 273 consecutive patients with CS were included. 28% presented with low CVR and 72% with high CVR. Within the entire study cohort, the risk of 30-day all-cause mortality did not differ between patients with high and low CVR (55% vs. 57%; log rank p = 0.727; HR = 0.942; 95% CI 0.663–1.338; p = 0.738). Even after multivariable adjustment, high CVR was not associated with an elevated risk of 30-day all-cause mortality (HR = 1.039; 95% CI 0.648–1.667; p = 0.873). The presence of arterial hypertension (55% vs. 58%; log rank p = 0.564; HR = 0.906; 95% CI 0.638–1.287; p = 0.582), diabetes mellitus (60% vs. 52%; log rank p = 0.215; HR = 1.213; 95% CI 0.881–1.671; p = 0.237) and a history of smoking (56% vs. 56%; log rank p = 0.725; HR = 0.945; 95% CI 0.679–1.315; p = 0.737) did not significantly influence short-term prognosis.. Only the absence of hyperlipidaemia significantly decreased the risk of all-cause mortality (65% vs. 51%; log rank p = 0.038; HR = 0.718; 95% CI 0.516–0.998; p = 0.049), which was no longer observed after multivariable adjustment (HR = 0.801; 95% CI 0.536–1.195; p = 0.277). In conclusion, neither the overall CVR nor individual CVR factors were associated with the risk of 30-day all-cause mortality in patients with CS. Full article

Background: Peripheral artery disease (PAD) remains a major issue in modern societies and affects more than 200 million people around the world. Endovascular methods have been evaluated to be safe and effective in limb salvage. The Supera is able to withstand increased compression, biomechanical stress and to have higher radial force. The objective of this study is to evaluate performance, durability and 3-year patency of Supera stent implantation in severe femoropopliteal disease. Methods: A retrospective real-world analysis was performed with consideration of 77 patients that had a Supera stent implanted with femoropopliteal atherosclerotic disease at a single center. Among the 77 individuals, 92 Supera stents were implanted. Analysis of patients’ demographics, lesions characteristics, reintervention rates and patency rates was performed. Results: The median follow-up was 33 months and ranged from 0 to 84 months. Chronic limb-threatening ischemia was observed among 43 patients. Mean lesion length was 152.8 ± 94.6 mm. Chronic total occlusions were observed in a majority of lesions. Overall, primary patency rates at 6, 12, 24 and 36 months were 85.0%, 73.6%, 59.2% and 53.2%, respectively. Conclusions: The Supera stent is effective in the management of long and complex lesions. The results of patency rates were evaluated to be worse among lesions extending to the popliteal artery. Full article

Purpose: This study aimed to investigate whether intravitreal aflibercept was safe and effective in patients with acute nonarteritic anterior ischemic optic neuropathy (NAION). Methods: This was a chart study of 25 individuals with acute NAION (25 eyes). An intravitreal injection of 2 mg/0.05 mL of aflibercept was administered to fifteen participants. The remaining ten patients in the control group were given standard care. The researchers measured the initial visual acuity, retinal nerve fiber layer thickness (RNFLT), and automated perimetry. During the follow-up period, the researchers measured the final visual acuity, RNFLT, automated perimetry, and side effects. Results: Visual acuity and visual field assessment were significantly improved in the study group, and optical coherence tomography testing demonstrated significant disc edema resolution. The therapy results differed significantly between the two groups regarding visual outcomes (F = 0.027, p = 0.039) and RNFLT decrease (F = 5.507, p = 0.003). However, the difference in visual field alterations was not significant (F = 0.724, p = 0.387). Conclusions: Intravitreal injection of aflibercept can significantly improve visual acuity and resolve disc edema in patients with acute NAION. Intravitreal aflibercept may be an alternative treatment for acute NAION. However, a large series investigation is needed to assess the long-term therapeutic benefit and safety of intravitreal aflibercept in patients with acute NAION. Full article

Background: We report a comparative analysis of extraperitoneal urethra-sparing robot-assisted simple prostatectomy (EUS-RASP) versus robot-assisted simple prostatectomy (RASP) using the Freyer approach for patients with a large prostate volume greater than 80 mL. Methods: A total of 32 patients underwent EUS-RASP, and 30 underwent RASP from April 2018 to November 2021. All the perioperative data and 6-month follow-up data were collected prospectively. We retrospectively evaluated baseline characteristics and functional outcomes, including International Prostate Symptom Scores (IPSSs) and quality of life (QOL), maximum flow rate, and post-void residual volume, between the two groups. Sexual function was analyzed in the EUS-RASP group. Results: The patients undergoing EUS-RASP and RASP had comparable baseline characteristics and functional outcomes. The EUS-RASP group showed a shorter operative time (123.4 ± 15.2 min vs. 133.7 ± 21.4 min, p = 0.034), length of hospital stay (2.9 ± 1.5 days vs. 4.6 ± 1.5 days, p = 0.001), and catheterization time (2.4 ± 1.7 days vs. 8.1 ± 2.4 days, p < 0.001). A total of 14/32 (43.8%) patients reported normal preoperative ejaculatory function in the EUS-RASP group, and 11/14 (78.6%) maintained antegrade ejaculation postoperatively. Conclusions: Extraperitoneal urethra-sparing RASP is an effective and feasible procedure that can improve voiding function and allow for the maintenance of ejaculatory function in patients with large prostates. Full article

Cardiomyopathies are a heterogeneous group of myocardial diseases representing the first cause of heart transplantation in children. Diagnosing and classifying the different phenotypes can be challenging, particularly in this age group, where cardiomyopathies are often overlooked until the onset of severe symptoms. Cardiovascular imaging is crucial in the diagnostic pathway, from screening to classification and follow-up assessment. Several imaging modalities have been proven to be helpful in this field, with echocardiography undoubtedly representing the first imaging approach due to its low cost, lack of radiation, and wide availability. However, particularly in this clinical context, echocardiography may not be able to differentiate from cardiomyopathies with similar phenotypes and is often complemented with cardiovascular magnetic resonance. The latter allows a radiation-free differentiation between different phenotypes with unique myocardial tissue characterization, thus identifying the presence and extent of myocardial fibrosis. Nuclear imaging and computed tomography have a complementary role, although they are less used in daily clinical practice due to the concern related to the use of radiation in pediatric patients. However, these modalities may have some advantages in evaluating children with cardiomyopathies. This paper aims to review the strengths and limitations of each imaging modality in evaluating pediatric patients with suspected or known cardiomyopathies. Full article

Background: Due to the rapid spread of the coronavirus disease-19 (COVID-19), most of the patients expressed a reluctance to undergo postoperative rehabilitation at a rehabilitation clinic. Therefore, in this scenario it was necessary to reshape the crucial role of postoperative rehabilitation of these patients. We conducted a telerehabilitation program based on an artificial intelligence brace (AI brace) which can monitor the progress of rehabilitation through an app and an internet server. Our hypothesis was that home-based telerehabilitation might provide clinical outcomes comparable to face-to-face, hospital-based rehabilitation programs in terms of effectiveness. Methods: A retrospective cohort study enrolled patients who received anterior cruciate ligament reconstruction (ACLR) between January and September 2020. Patients were divided into two groups: the tele-AI group received telerehabilitation with an AI brace while the FTF group had face-to-face, hospital-based rehabilitation. Clinical knee functional scores and Tegner Activity Scale (TAS) were assessed and analyzed until 12 months after the operation. Results: The tele-AI group had higher IKDC scores at 3 months (p = 0.0443) and 6 months (p = 0.0052) after surgery and higher KOOS scores at 1 month (p = 0.0365) and 6 months (p = 0.0375) after surgery. However, no significant difference between the two groups was detected at the end of the follow-up. The tele-AI group had higher TAS than FTF group after 1 year. Conclusions: Telerehabilitation after ACLR seems to provide a superior short-term outcome compared to hospital-based rehabilitation during the COVID-19 pandemic. Full article

A considerable number of patients with angina or myocardial ischemia have no significant coronary artery disease on invasive angiography. In recent years, several steps towards a better comprehension of the pathophysiology of these conditions, angina or ischemia with non-obstructive coronary arteries (ANOCA/INOCA), have been made. Nevertheless, several gaps in knowledge still remain. This review is intended to provide a comprehensive overview of ANOCA and INOCA, with a particular focus on pathophysiology, recent diagnostic innovations, gaps in knowledge and treatment modalities. Full article

Background: The aim of this study was to assess the correlation between the overall rest–stress distance measured by transperineal ultrasound (TPUS) and Q-tip test angle in women with urodynamic stress incontinence (USI), and determine a cut-off value of rest–stress distance for predicting urethral hypermobility (UH). Methods: Women with USI scheduled for mid-urethral sling surgery were retrospectively recruited. UH was defined as a Q-tip angle more than or equal to 30 degrees. Ultrasonic measurement of the overall rest–stress distance was defined as the linear distance of bladder-neck position change from resting status to maximal strain. Results: Among the 132 enrolled women, the Pearson correlation coefficient between the overall rest–stress distance in TPUS and Q-tip test angle was 0.9104 (95% CI, 0.8758–0.9357, p < 0.001). In receiver-operating-characteristic-curve analysis, a rest–stress distance of more than 13.3 mm was an optimal cut-off value to predict UH (sensitivity = 76.47%, specificity = 93.3%; area = 0.937, 95% confidence interval: 0.881–0.972). Conclusions: The overall rest–stress distance in TPUS correlated well with the Q-tip test angle, indicating that it can be an alternative method for the assessment of USI. A rest–stress distance of more than 13.3 mm was an optimal cut-off value to predict UH in women with USI. Full article

Purpose: To investigate the prevalence of geographic atrophy (GA) in advanced age-related macular degeneration (AMD) and the proportion of eyes that would meet the indication criteria for treatment with the first intravitreal anti-C3 agent (pegcetacoplan). Methods: This retrospective cross-sectional study included all AMD patients who visited the Macular-Retina-Centre Oberkassel in 2021. Eyes were classified according to AMD stages. Eyes with GA were divided into two groups regarding foveal involvement. Baseline factors were compared between eyes with foveal GA (FGA) and eyes with non-foveal GA (NFGA) to identify predictive factors for foveal involvement. Results: A total of 2033 eyes from 1027 patients were included. AMD stage was early in 296 (14.5%) cases, intermediate in 368 (18.1%) cases, and advanced in 1249 (61.4%) cases. A total of 1204 (60%) eyes had GA [932 (77%) FGA and 272 (23%) NFGA], while 125 eyes (27.4% from eyes with advanced dry AMD) met the indication criteria for treatment with intravitreal pegcetacoplan. The proportion of eyes with neovascular AMD was significantly higher in the FGA group compared to the NFGA group [598 (64.2%) vs. 152 (55.8%), p = 0.01]. Conclusions: At least a quarter of eyes with advanced AMD would be suitable for the upcoming intravitreal pegcetacoplan therapy. Foveal involvement of GA in advanced AMD seems to be more likely in neovascular AMD than in dry AMD. Full article

Background: The aim of this study was to demonstrate that both neurological and hepatic symptoms respond to copper chelation therapy in Wilson disease (WD). However, the time course of their recovery is different. Methods: Eighteen patients with neurological WD from a single specialized center who had been listed for liver transplantation during the last ten years and two newly diagnosed homozygous twins were recruited for this retrospective study. The mean duration of conventional treatment was 7.3 years (range: 0.25 to 36.2 years). A custom Wilson disease score with seven motor items, three non-motor items, and 33 biochemical parameters of the blood and urine, as well as the MELD score, was determined at various checkup visits during treatment. These data were extracted from the charts of the patients. Results: Treatment was initiated with severity-dependent doses (≥900 mg) of D-penicillamine (DPA) or triethylene-tetramin-dihydrochloride (TRIEN). The motor score improved in 10 and remained constant in 8 patients. Worsening of neurological symptoms was observed only in two patients who developed comorbidities (myasthenia gravis or hemispheric stroke). The neurological symptoms continuously improved over the years until the majority of patients became only mildly affected. In contrast to this slow recovery of the neurological symptoms, the MELD score and liver enzymes had already started to improve after 1 month and rapidly improved over the next 6 months in 19 patients. The cholinesterase levels continued to increase significantly (p < 0.0074) even further. One patient whose MELD score indicated further progression of liver disease received an orthotopic liver transplantation 3 months after the diagnosis of WD and the onset of DPA treatment. Conclusions: Neurological and hepatic symptoms both respond to copper chelation therapy. For patients with acute liver failure, the first 4 months are critical. This is the time span in which patients have to wait either for a donor organ or until significant improvement has occurred under conventional therapy. For patients with severe neurological symptoms, it is important that they are treated with fairly high doses over several years. Full article

We hypothesize that (1) a significant pre-ECMO liver impairment, which is evident in the presence of pre-ECMO acute liver injury and a higher pre-ECMO MELD (model for end-stage liver disease) score, is associated with increased mortality; and (2) the requirement of veno-veno-arterial (V-VA) ECMO support is linked to a higher prevalence of pre-ECMO acute liver injury, a higher pre-ECMO MELD score, and increased mortality. We analyze 187 ECMO runs (42 V-VA and 145 veno-venous (V-V) ECMO) between January 2017 and December 2020. The SAPS II score is calculated at ICU admission; hepatic function and MELD score are assessed at ECMO initiation (pre-ECMO) and during the first five days on ECMO. SOFA, PRESERVE and RESP scores are calculated at ECMO initiation. Pre-ECMO cardiac failure, acute liver injury, ECMO type, SAPS II and MELD, SOFA, PRESERVE, and RESP scores are associated with mortality. However, only the pre-ECMO MELD score independently predicts mortality (p = 0.04). In patients with a pre-ECMO MELD score > 16, V-VA ECMO is associated with a higher mortality risk (p = 0.0003). The requirement of V-VA ECMO is associated with the development of acute liver injury during ECMO support, a higher pre-ECMO MELD score, and increased mortality. Full article

Robotic surgery may offer significant advantages for treating extraperitoneal rectal cancer. Although laparoscopy has been shown to be safe and effective, laparoscopic total mesorectal excision (TME) remains technically challenging and is still performed in selected centers. Robotic anterior resection (RAR) may overcome the drawback of conventional laparoscopy, providing high-quality surgery with favorable oncological outcomes. Moreover, recent data show how RAR offers clinical and oncological benefits when affording difficult TMEs, such as low and advanced rectal tumors, in terms of complication rate, specimen quality, recurrence rate, and survival. This series aims to review the most recent and relevant literature, reporting mid- and long-term oncological outcomes and focusing on minimally invasive RAR for low rectal cancer. Full article

The anterior cruciate ligament (ACL) is the most injured ligament of the knee, and the treatment of choice is usually ACL reconstruction. Kinesiophobia refers to an irrational and paralyzing fear of movement caused by the feeling of being prone to injury or reinjury. The aim of the present study is to evaluate the relationship between preoperative and postoperative kinesiophobia with postoperative outcomes of ACL-R evaluated through SF-36, ACL-RSI, KOOS, and OKS scores. Included patients all underwent ACL reconstruction. The preoperative TSK-13 questionnaire and six-month postoperative TSK-13, ACL-RSI, SF-36, KOOS, and OKS questionnaires were assessed in included patients. Normal distribution was assessed using the Shapiro–Wilk test. The study included 50 patients who filled out the questionnaires at the 6-month postoperative follow-up. Correlations between preoperative TSK-13 and postoperative outcome measures revealed a low–moderate negative correlation between preoperative TSK-13 and SF-36 PCS at 6-month follow-up. Correlations between postoperative TSK-13 and postoperative outcome measures revealed a high negative correlation between preoperative TSK-13 and ACL-RSI, KOOS Symptoms, KOOS Pain, KOOS ADL, and OKS at 6-month follow-up. Preoperative and postoperative kinesiophobia were found to influence postoperative ACL-R outcomes negatively, more specifically an increase in kinesiophobia showed a statistically significant correlation with worse postoperative SF-36 PCS scores in patients. Full article

Background: Reverse triggered breath (RTB) has been extensively described during assisted-controlled modes of ventilation. We aimed to assess whether RTB occurs during Pressure Support Ventilation (PSV) and Neurally Adjusted Ventilatory Assist (NAVA) at varying depths of propofol sedation. Methods: This is a retrospective analysis of a prospective crossover randomized controlled trial conducted in an Intensive Care Unit (ICU) of a university hospital. Fourteen intubated patients for acute respiratory failure received six trials of 25 minutes randomly applying PSV and NAVA at three different propofol infusions: awake, light, and deep sedation. We assessed the occurrence of RTBs at each protocol step. The incidence level of RTBs was determined through the RTB index, which was calculated by dividing RTBs by the total number of breaths triggered and not triggered. Results: RTBs occurred during both PSV and NAVA. The RTB index was greater during PSV than during NAVA at mild (1.5 [0.0; 5.3]% vs. 0.6 [0.0; 1.1]%) and deep (5.9 [0.7; 9.0]% vs. 1.7 [0.9; 3.5]%) sedation. Conclusions: RTB occurs in patients undergoing assisted mechanical ventilation. The level of propofol sedation and the mode of ventilation may influence the incidence of RTBs. Full article

Background: MTHFR polymorphism has been inconsistently linked to thrombotic events—some studies have shown its contribution to venous thrombosis, arterial thrombosis, and ischemic stroke, whereas others have found no statistically significant correlation between them. Methods: A descriptive case series study was performed in the Neonatal Intensive Care Unit of “Marie Sklodowska Curie” Emergency Clinical Hospital for Children in Bucharest, Romania. Results: All patients had positive results for MTHFR variants; 14 patients were positive for compound heterozygosity, 13 patients for MTHFR C677T (seven of which were homozygous), and 13 patients for MTHFR A1298C (three of which were homozygous). Eighteen patients received anticoagulants (heparin, enoxaparin, or bivalirudin), and thrombolytics (alteplase) were administered in six cases. In one case, a thrombectomy was performed; in another, vascular plasty was undertaken. Only in six cases was complete revascularization possible. Incomplete revascularization occurred for one patient with a negative outcome. Conclusion: The particularity of this case series is that every patient in our unit who developed thrombi had a positive genetic result for MTHFR mutations. MTHFR mutations should be regarded as a thrombotic risk factor for critically ill patients, and screening for MTHFR mutations should be performed in every admitted patient to intensive care units, thus achieving the prevention of thrombi. Full article

To summarize the evidence on non-hemorrhagic adrenal infarction (NHAI) and identify questions arising in diagnosis and management, cases in the PubMed database were merged with our case series. A total of 92 publications were retrieved, 15 of which reported on NHAI during pregnancy. Including the four in our case series, 24 cases have been described so far. Severe, unremitting pain requiring opioid analgesia was the leading symptom, often combined with nausea and vomiting. Laboratory results were non-contributory in most cases. Diagnosis was established via MRI in nine cases (37.5%) and via CT in six (25%); nine patients (37.5%) underwent both investigations. Location was predominantly on the right side (n = 16, 66.7%). In addition to analgesia, anticoagulation with heparin was commenced in 18 cases (75%). When thrombophilia screening was performed, major thrombogenic polymorphisms were detected in six cases (33.3%). One woman developed signs of adrenal insufficiency. The reported perinatal outcome was unremarkable. Unilateral NHAI has emerged as a rare but important cause of severe abdominal pain in pregnancy. The threshold to perform an MRI in pregnant women with characteristic clinical findings should be low. To prevent fetal radiation exposure, diagnostic imaging via CT should be avoided. In addition to symptomatic treatment with opioid analgesia, initiation of anticoagulant treatment should be strongly considered. Full article

The acute phase of COVID-19 often leaves patients with persistent pulmonary deficits. Pulmonary Rehabilitation (PR) has been recommended as an essential part of post-acute COVID-19 management. In light of the global pandemic, telerehabilitation has been increasingly employed to deliver PR. This systematic review aimed to evaluate the effectiveness of telemedicine-driven PR in patients recovering from the acute phase of COVID-19, assessing variations in telerehabilitation practices and identifying the degree of change in mental health, physical health, quality of life, and lung function. A systematic search was conducted across PubMed, Web of Science, Cochrane, and Scopus up until April 2023. Studies focusing on telerehabilitation in PR for post-acute COVID-19 patients with outcomes including pulmonary function, exercise capacity, and quality of life were included after careful assessment of this study’s protocol. The selection process involved careful scrutiny of abstracts and full texts, and the quality assessment was performed using the National Heart, Lung, and Blood Institute (NHLBI) tool. Seven studies, published between 2021 and 2022, involving a total of 412 patients, were included. The evaluated telerehabilitation programs stretched between 4 and 10 weeks, involving a mobile app or video connection with the patient, integrating a mix of aerobic and resistance training, breathing exercises, functional activities, and muscle strengthening. Findings revealed that telemedicine-driven PR significantly improved physical health, measured by the step test score (73 vs. 71), 6MWD (30.2 vs. 17.1) and BPAQ, mental health evaluated by SF-12 (6.15 vs. 4.17) and PHQ-4, quality of life measured by the SF-12 (7.81 vs. 3.84), SGRQ (31.5 vs. 16.9), and CAT scores, and some parameters of pulmonary function in post-acute COVID-19 patients (mMRC, STST, and MVV). This review substantiates the potential of telemedicine-driven PR to improve various health outcomes in post-acute COVID-19 patients. The findings underscore the importance of integrating telerehabilitation into the management of post-acute COVID-19 and call for further exploration of its long-term effects, cost-effectiveness, and best practices. Full article

Background: Among patients with ulcerative colitis, 30–50% receive corticosteroids within the first five years after diagnosis. We aimed to reconsider their effectiveness in the context of the biologic era. Methods: In this prospective, multicenter study, patients with active ulcerative colitis (Lichtiger score ≥ 4) were eligible if initiating systemic corticosteroids. The primary endpoint was clinical response (decrease in the Lichtiger score of ≥50%) at week 4. Secondary endpoints included combined response defined as clinical response and any reduction in elevated biomarkers (CRP and/or calprotectin). Steroid dependence was assessed after three months. Results: A total of 103 patients were included. Clinical response was achieved by 73% of patients, and combined response by 68%. A total of 15% of patients were steroid-dependent. Activity of colitis did not influence short-term response to treatment but increased the risk for steroid dependence. Biologic-naïve patients responded better than biologic-experienced patients. Past smoking history (OR 5.38 [1.71, 20.1], p = 0.003), hemoglobin levels (OR 0.76 [0.57, 0.99] for higher levels, p = 0.045), and biologic experience (OR 3.30 [1.08, 10.6], p = 0.036) were independently associated with nonresponse. Conclusion: Disease activity was not associated with short-term response to systemic corticosteroids but was associated with steroid dependence in patients with active ulcerative colitis. Exposure to biologics negatively affects response rates. Full article

This study evaluates the performance of a fully automated algorithm to detect active inflammation in the form of bone marrow edema (BME) in iliac and sacral bones, depending on the quality of the coronal oblique plane in patients with axial spondyloarthritis (axSpA). The results were assessed based on the technical correctness of MRI examination of the sacroiliac joints (SIJs). A total of 173 patients with suspected axSpA were included in the study. In order to verify the correctness of the MRI, a deviation angle was measured on the slice acquired in the sagittal plane in the T2-weighted sequence. This angle was located between the line drawn between the posterior edges of S1 and S2 vertebrae and the line that marks the actual plane in which the slices were acquired in T1 and STIR sequences. All examinations were divided into quartiles according to the deviation angle measured in degrees as follows: 1st group [0; 2.2], 2nd group (2.2; 5.7], 3rd group (5.7; 10] and 4th group (10; 29.2]. Segmentations of the sacral and iliac bones were acquired manually and automatically using the fully automated algorithm on the T1 sequence. The Dice coefficient for automated bone segmentations with respect to reference manual segmentations was 0.9820 (95% CI [0.9804, 0.9835]). Examinations of BME lesions were assessed using the SPARCC scale (in 68 cases SPARCC > 0). Manual and automatic segmentations of the lesions were performed on STIR sequences and compared. The sensitivity of detection of BME ranged from 0.58 (group 1) to 0.83 (group 2) versus 0.76 (total), while the specificity was equal to 0.97 in each group. The study indicates that the performance of the algorithm is satisfactory regardless of the deviation angle. Full article

Background: Catheter ablation (CA) has become safe and efficient for the treatment of patients with ventricular extrasystolic beats (VEBs). The three-dimensional electroanatomic mapping (EAM) system allows the elimination of fluoroscopy time during CA procedures. Non-fluoroscopy CA is a challenging procedure requiring intimate knowledge of cardiac anatomy in patients with VEBs. The study aimed to evaluate the efficacy and safety of the non-fluoroscopy CA using the EAM system in patients with VEBs. Methods: Completely fluoroless CA of VEBs guided by EAM was performed in 86% (94 out of 109) of consecutive patients with VEBs. The remaining 15 patients underwent conventional fluoroscopy-guided CA. Demographic and clinical baseline characteristics, procedure parameters, and following complications were obtained from the medical records. Primary outcomes were the acute procedural success rate, the permanent success rate (6-month follow-up), complications, and procedure time. Results: There were no significant differences between groups regarding baseline characteristics. Acute procedural success was achieved in 85 patients (90%) in the non-fluoroscopy group and in 14 patients (93%) in the fluoroscopy group (ns). A long-term success rate was achieved in 82 patients (87%) in the non-fluoroscopy group and in 14 (82%) patients in the fluoroscopy group (ns). The median procedure time was 85 min in the non-fluoroscopy group and 120 min in the fluoroscopy group (p = 0.029). There was only one major complication in the non-fluoroscopy group (ns). Conclusions: Completely fluoroless CA of VEBs guided by EAM is a feasible, safe, and efficient procedure. Full article

Background: A few prospective trials and case series have suggested that hyperbaric oxygen therapy (HBOT) may be efficacious for the treatment of severe COVID-19, but safety is a concern for critically ill patients. We present an interim analysis of the safety of HBOT via a randomized controlled trial (COVID-19-HBO). Methods: A randomized controlled, open-label, clinical trial was conducted in compliance with good clinical practice to explore the safety and efficacy of HBOT for severe COVID-19 in critically ill patients with moderate acute respiratory distress syndrome (ARDS). Between 3 June 2020, and 17 May 2021, 31 patients with severe COVID-19 and moderate-to-severe ARDS, a ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO₂/FiO₂) < 26.7 kPa (200 mmHg), and at least two defined risk factors for intensive care unit (ICU) admission and/or mortality were enrolled in the trial and randomized 1:1 to best practice, or HBOT in addition to best practice. The subjects allocated to HBOT received a maximum of five treatments at 2.4 atmospheres absolute (ATA) for 80 min over seven days. The subjects were followed up for 30 days. The safety endpoints were analyzed. Results: Adverse events (AEs) were common. Hypoxia was the most common adverse event reported. There was no statistically significant difference between the groups. Numerically, serious adverse events (SAEs) and barotrauma were more frequent in the control group, and the differences between groups were in favor of the HBOT in PaO₂/FiO₂ (PFI) and the national early warning score (NEWS); statistically, however, the differences were not significant at day 7, and no difference was observed for the total oxygen burden and cumulative pulmonary oxygen toxicity dose (CPTD). Conclusion: HBOT appears to be safe as an intervention for critically ill patients with moderate-to-severe ARDS induced by COVID-19. Clinical trial registration: NCT04327505 (31 March 2020) and EudraCT 2020-001349-37 (24 April 2020). Full article

Central sensitization cannot be directly demonstrated in humans and thus a gold standard is missing. Therefore, we used human assumed central sensitization (HACS) when associated with humans. The central sensitization inventory (CSI) is a screening questionnaire for addressing symptoms that are associated with HACS. This cross-sectional study compared patients with chronic pain and at least one central sensitivity syndrome with healthy, pain-free controls via ROC analyses. Analyses were performed for all participants together and for each sex separately. Regression analyses were performed on patients with chronic pain with and without central sensitivity syndromes. Based on 1730 patients and 250 healthy controls, cutoff values for the CSI for the total group were established at 30 points: women: 33 points; men: 25 points. Univariate and multivariate regression analyses were used to identify possible predictors for the CSI score in 2890 patients with chronic pain. The CSI score is associated with all independent factors and has a low association with pain severity in women and a low association with pain severity, age, and body mass index in men. The newly established CSI cutoff values are lower than in previous studies and different per sex, which might be of clinical relevance in daily practice and importance in research. Full article

Background: B cells are central to the pathogenesis of systemic lupus erythematosus (SLE). We aimed to analyze the efficacy and safety of new B cell-targeted drug therapies for SLE. Methods: A systematic review of randomized controlled trials (RCTs) and reference lists of relevant articles published from inception to 2022 were selected from PubMed, Scopus and Web of Science databases. Random effects meta-analyses were performed to estimate an overall effect size for the risk of adverse events (AEs) and serious adverse events (SAEs) with belimumab and tabalumab treatment. Heterogeneity was assessed using the I² statistic and meta-regression. Funnel asymmetry was evaluated using Egger’s test. Results: This study included 13 RCTs, of which three showed high risk of bias. Egger’s test showed no asymmetry. The risk of SAEs and AEs was lower in the treatment group with belimumab treatment. The risk of AEs for tabalumab treatment was lower in the treatment group and lower for SAEs. Conclusion: Belimumab and tabalumab therapies are effective and safe in the treatment of SLE, although tabalumab does not show sufficient statistical power. Advances in understanding the underlying mechanisms of SLE will be directed towards correlating clinical manifestations with specific pathogenic pathways and the development of precision medicine. Full article