J. Clin. Med., Volume 10, Issue 13 (July-1 2021) – 262 articles

Worldwide, there are millions of people who have been diagnosed with osteoporosis, a bone disease that increases the risk of fracture due to low bone mineral density and deterioration of bone architecture. In the US alone, there are approximately ten million men and women diagnosed with osteoporosis and this number is still growing. Diagnosis is made by measuring bone mineral density. Medications used for the treatment of osteoporosis are bisphosphonates, denosumab, raloxifene, and teriparatide. Recently, romosozumab has been added as well. In recent years, a number of advances have been made in the field of diagnostic methods and the diverse treatment options for osteoporosis. Despite these advances and a growing incidence of osteoporosis, there is a large group being left undertreated or even untreated. This group of the under/untreated has been called the treatment gap. Concerns regarding rare side effects of the medications, such as osteonecrosis of the jaw, have been reported to be one of the many causes for the treatment gap. Also, this group seems not to be sufficiently informed of the major benefits of the treatment and the diversity in treatment options. Knowledge of these could be very helpful in improving compliance and hopefully reducing the gap. In this paper, we summarize recent evidence regarding the efficacy of the various treatment options, potential side effects, and the overall benefit of treatment. Full article

Huntington’s disease (HD) is an autosomal dominant genetic disease that can be divided into preclinical and symptomatic stages. Due to the diverse HD phenotype, there is an urgent need to identify markers that would independently assess its severity. The aim of this study was to evaluate the use of plasma levels of TGF-β1 in the assessment of HD severity. One hundred HD patients and 40 healthy volunteers were included in the study. All HD patients underwent neurological and cognitive function assessment. TGF-β1 levels were determined in the plasma of all patients. The correlations between TGF-β1 levels and clinical profile and HD severity were also investigated. In symptomatic patients, cognitive decline was demonstrated, while in preclinical patients, no symptoms were found. Plasma levels of TGF-β1 in HD patients did not differ significantly from the control group and did not change with the progression of the disease. In addition, TGF-β1 levels also did not correlate with the severity of motor dysfunction. Positive correlations between plasma TGF-β1 concentration and intensity of cognitive impairment were found, but only in the early disease stage. There was no clear benefit in assessing plasma TGF-β1 levels in HD patients as a marker of disease severity. Full article

Sex differences exist in the incidence and presentation of many pregnancy complications, including but not limited to pregnancy loss, spontaneous preterm birth, and fetal growth restriction. Sex differences arise very early in development due to differential gene expression from the X and Y chromosomes, and later may also be influenced by the action of gonadal steroid hormones. Though offspring sex is not considered in most prenatal diagnostic or therapeutic strategies currently in use, it may be beneficial to consider sex differences and the associated mechanisms underlying pregnancy complications. This review will cover (i) the prevalence and presentation of sex differences that occur in perinatal complications, particularly with a focus on the placenta; (ii) possible mechanisms underlying the development of sex differences in placental function and pregnancy phenotypes; and (iii) knowledge gaps that should be addressed in the development of diagnostic or risk prediction tools for such complications, with an emphasis on those for which it would be important to consider sex. Full article

Fibrin is a major component of thrombi formed on the surface of atherosclerotic plaques. Fibrin accumulation as a consequence of local blood coagulation activation takes place inside atherosclerotic lesions and contributes to their growth. The imbalance between thrombin-mediated fibrin formation and fibrin degradation might enhance atherosclerosis in relation to inflammatory states reflected by increased fibrinogen concentrations, the key determinant of fibrin characteristics. There are large interindividual differences in fibrin clot structure and function measured in plasma-based assays and in purified fibrinogen-based systems. Several observational studies have demonstrated that subjects who tend to generate denser fibrin networks displaying impaired clot lysis are at an increased risk of developing advanced atherosclerosis and arterial thromboembolic events. Moreover, the majority of cardiovascular risk factors are also associated with unfavorably altered fibrin clot properties, with their improvement following effective therapy, in particular with aspirin, statins, and anticoagulant agents. The prothrombotic fibrin clot phenotype has been reported to have a predictive value in terms of myocardial infarction, ischemic stroke, and acute limb ischemia. This review article summarizes available data on the association of fibrin clot characteristics with atherosclerotic vascular disease and its potential practical implications. Full article

Background: The risk of pulmonary embolism (PE) has not been studied in older patients affected by COVID-19. We aimed to assess PE incidence and risk factors in a population of older patients infected with SARS-CoV-2. Methods: An ambispective, observational cohort study. A total of 305 patients ≥ 75 years old had the SARS-CoV-2 infection from March to May 2020. The incidence rate of PE was estimated as the proportion of new cases within the whole sample. Youden’s index was used to assess the cutoff point of D-dimer. To select factors associated with the risk of PE, time-to-event analyses were performed using cause-specific hazard models. Results: In total, 305 patients with a median age of 87 years (62.3% female) were studied; 67.9% were referred from nursing homes and 90.4% received any type of anticoagulation. A total of 64.9% showed frailty and 44% presented with dementia. The PE incidence was 5.6%. The cutoff value of a D-dimer level over 2.59 mg/L showed a sensitivity of 82.4% and specificity of 73.8% in discriminating a PE diagnosis. In the multivariate analysis, the factors associated with PE were previous oncological events and D-dimer levels. Conclusions: The PE incidence was 5.6%, and major risk factors for PE were oncological antecedents and increased plasma D-dimer levels. Full article

Background: Vedolizumab (vedo) is effective for induction and maintenance of remission in adults with inflammatory bowel disease (IBD). Pediatric data are still limited, especially for the youngest children with very early onset disease (VEO-IBD). The aim of this study was to assess the safety and efficacy of vedo in VEO-IBD. Methods: We performed a retrospective review of pediatric IBD patients with VEO-IBD (defined as aged <6 years) receiving vedo. Data on demographics, disease behavior, activity, and previous treatments/surgeries were collected. Disease activity was assessed using the pediatric Crohn’s disease (CD) activity index (PCDAI) for CD or pediatric ulcerative colitis (UC) activity index (PUCAI) for UC. Primary outcome was clinical response after induction therapy with vedolizumab (4th dose week). It was defined as a decrease in PCDAI of at least 12.5 points between baseline and 4th dose week for CD, and a decrease in PUCAI of at least 20 points between baseline and this time for UC. Descriptive statistics were performed to analyze the data. Results: The study included 16 patients with VEO-IBD who have received vedo: 4/16 (25%) with CD, and 12/16 (75%) with UC at the median age of diagnosis 33.7 months (6.6 months–4.5 years). Median age at vedo initiation was 6.5 years (2.2–16.5 years). Among the analyzed individuals, 56.25% had failed more than one anti-tumor necrosis factor (TNF) alfa agent. Clinical response at 4th dose week was observed in 9/16 (56.3%) patients: mean baseline PCDAI score was 34.4 ± 1.9 and 10.6 ± 1.8 after induction therapy with vedo, while PUCAI score was 26 ± 6 vs. 18 ± 8, respectively. There was improvement in patients’ nutritional state: at baseline 2/16 (12.5%) children had body mass index (BMI) below 1 percentile and no child had such BMI after induction therapy with vedo. No infusion reactions or serious adverse events/infections were reported. Conclusion: Vedolizumab is safe and effective in the medical management of pediatric patients with VEO-IBD. Full article

Background: The Peptest^TM is a non-invasive diagnostic test for measuring the pepsin concentration in saliva, which is thought to correlate with laryngopharyngeal reflux (LPR). The aim of this study was to investigate the diagnostic value of the Peptest in detecting LPR based on 24-h multichannel intraluminal impedance-pH (MII-pH) monitoring using several hypopharyngeal reflux episodes as criterion for LPR. Methods: Patients with suspected LPR were examined with the Reflux Symptom Index (RSI), Reflux Finding Score (RFS), fasting Peptest, and MII-pH monitoring. We calculated the accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the Peptest, RSI, and RFS based on the threshold of one and six hypopharyngeal reflux episodes. Results: Altogether, the data from 46 patients were analyzed. When one hypopharyngeal reflux episode was used as a diagnostic threshold for LPR, the accuracy, sensitivity, specificity, PPV, and NPV were, respectively, as follows: 35%, 33%, 100%, 100%, and 3%, for the Peptest; 39%, 40%, 0%, 95%, and 0%, for the RSI; and 57%, 58%, 0%, 96%, and 0%, for the RFS. The accuracy, sensitivity, specificity, PPV, and NPV of the Peptest for diagnosing gastroesophageal reflux disease (GERD) were 46%, 27%, 63%, 40.0%, and 48%, respectively. Conclusions: A positive Peptest is highly supportive of a pathological LPR diagnosis. However, a negative test could not exclude LPR. Full article

In response to an increased afterload in pulmonary arterial hypertension (PAH), the right ventricle (RV) adapts by remodeling and increasing contractility. The idea of coupling refers to maintaining a relatively constant relationship between ventricular contractility and afterload. Twenty-eight stable PAH patients (mean age 49.5 ± 15.5 years) were enrolled into the study. The follow-up time of this study was 58 months, and the combined endpoint (CEP) was defined as death or clinical deterioration. We used echo TAPSE as a surrogate of RV contractility and estimated systolic pulmonary artery pressure (sPAP) reflecting RV afterload. Ventricular–arterial coupling was evaluated by the ratio between these two parameters (TAPSE/sPAP). In the PAH group, the mean pulmonary artery pressure (mPAP) was 47.29 ± 15.3 mmHg. The mean echo-estimated TAPSE/sPAP was 0.34 ± 0.19 mm/mmHg and was comparable in value and prognostic usefulness to the parameter derived from magnetic resonance and catheterization (ROC analysis). Patients who had CEP (n = 21) had a significantly higher mPAP (53.11 ± 17.11 mmHg vs. 34.86 ± 8.49 mmHg, p = 0.03) and lower TAPSE/sPAP (0.30 ± 0.21 vs. 0.43 ± 0.23, p = 0.04). Patients with a TAPSE/sPAP lower than 0.25 mm/mmHg had worse prognosis, with log-rank test p = 0.001. the echocardiographic estimation of TAPSE/sPAP offers an easy, reliable, non-invasive prognostic parameter for the comprehensive assessment of hemodynamic adaptation in PAH patients. Full article

Down syndrome (DS) is a genetic disorder caused by the triplication of human chromosome 21, which results in neurological and physiological pathologies. These deficits increase during aging and are exacerbated by cognitive decline and increase of Alzheimer’s disease (AD) neuropathology. A nontoxic, noninvasive treatment, maternal choline supplementation (MCS) attenuates cognitive decline in mouse models of DS and AD. To evaluate potential underlying mechanisms, laser capture microdissection of individual neuronal populations of MCS offspring was performed, followed by RNA sequencing and bioinformatic inquiry. Results at ~6 months of age (MO) revealed DS mice (the well-established Ts65Dn model) have significant dysregulation of select genes within the Type 2 Diabetes Mellitus (T2DM) signaling pathway relative to normal disomic (2N) littermates. Accordingly, we interrogated key T2DM protein hormones by ELISA assay in addition to gene and encoded protein levels in the brain. We found dysregulation of adiponectin (APN) protein levels in the frontal cortex of ~6 MO trisomic mice, which was attenuated by MCS. APN receptors also displayed expression level changes in response to MCS. APN is a potential biomarker for AD pathology and may be relevant in DS. We posit that changes in APN signaling may be an early marker of cognitive decline and neurodegeneration. Full article

Transapical (TA) TAVR is known to be associated with increased mortality and vascular complications compared with transfemoral (TF) TAVR in high-risk and inoperable patients. However, safe alternative access methods remain crucial. We aimed to (1) evaluate the 30-day and 1-year outcomes comparing TA and TF TAVR in patients with an STS-PROM of <4% deemed inoperable and (2) determine dependent and independent predictors for all-cause one-year mortality. Data were collected from a single-center registry consisting of 340 eligible patients. One-to-one propensity score matching was performed (n = 50 TA, n = 50 TF). Primary endpoints were all-cause mortality, stroke, and major bleeding. Predictors for all-cause one-year mortality were evaluated. Thirty-day mortality (TF vs. TA: 0.0% vs. 4.0%; p = 0.153) was comparable in both cohorts. One-year all-cause mortality was twice as high in TA patients (TF vs. TA: 10.0% vs. 20.0%, p logrank = 0.165, HR 2.10). Cerebrovascular events and major bleeding during one-year follow-up were similar. The multivariate analysis identified hemoglobin <12 g/dL at admission and dual antiplatelet therapy as strong predictors for one-year mortality. Although femoral access is the primary access with favorable 30-day and 1-year results, transapical access was successful for patients unsuitable for TF TAVR, showing acceptable short- and mid-term results in inoperable patients with low-risk profiles. Full article

The well-known immunomodulatory and regenerative properties of mesenchymal stromal cells (MSCs) are the reason why they are being used for the treatment of many diseases. Because they are considered hypoimmunogenic, MSCs treatments are performed without considering histocompatibility barriers and without anticipating possible immune rejections. However, recent preclinical studies describe the generation of alloantibodies and the immune rejection of MSCs. This has led to an increasing number of clinical trials evaluating the immunological profile of patients after treatment with MSCs. The objective of this systematic review was to evaluate the generation of donor specific antibodies (DSA) after allogeneic MSC (allo-MSC) therapy and the impact on safety or tolerability. Data from 555 patients were included in the systematic review, 356 were treated with allo-MSC and the rest were treated with placebo or control drugs. A mean of 11.51% of allo-MSC-treated patients developed DSA. Specifically, 14.95% of these patients developed DSA and 6.33% of them developed cPRA. Neither the production of DSA after treatment nor the presence of DSA at baseline (presensitization) were correlated with safety and/or tolerability of the treatment. The number of doses administrated and human leucocyte antigen (HLA) mismatches between donor and recipient did not affect the production of DSA. The safety of allo-MSC therapy has been proved in all the studies and the generation of alloantibodies might not have clinical relevance. However, there are very few studies in the area. More studies with adequate designs are needed to confirm these results. Full article

Background The knee is one of the joints in the human body that is most susceptible of osteoarthritis (OA). In the case of advanced-stage OA, total knee arthroplasty (TKA) is a treatment of choice. One modern physiotherapeutic method to support the treatment in the early postsurgical period is Kinesio Taping (KT). The aim of this study is to evaluate the efficacy of KT on swollen subcutaneous tissue after TKA. Materials and methods. The studied group consisted of 23 patients who had received TKA. The mean BMI was 30.60 ± 4.91, and KT was applied between the 3rd and 8th day of the early postoperative period. The control group was constituted by 22 patients who had received TKA. The mean BMI was 30.41 ± 6.00, and KT was not applied. On the 3rd and 8th day after TKA, in all patients, the swelling of the shin, range of motions (ROM), and pain were measured using ultrasound, a goniometer, and a VAS scale, respectively. Results. In the KT group, the lateral measurement at the top of the head of the fibula significantly decreased between the 3rd and 8th day (11.47 ± 0.76 vs. 9.76 ± 0.77; p = 0.0004). The knee flexion angle on day 3 was statistically significantly different from that on day 8 (48.61 ± 3.08 vs. 72.74 ± 3.92; p = 0.00004). The evaluation results for severity of pain using the VAS scale on day 3 were statistically significantly higher than those on day 8 (5.74 ± 0.25 vs. 4.30 ± 0.25; p = 0.00006). In the group of patients to whom KT was not applied, the lateral measurement at the top of the head of the fibula on day 3 was not statistically significantly different from that on day 8 (10.323 ± 0.828 vs. 10.273 ± 0.995; p = 0.9227). The knee flexion angle in the group that did not receive KT on day 3 was statistically significantly different from that on day 8 (45.182 ± 3.654 vs. 59.909 ± 4.817; p = 0.0006). The severity of pain evaluated using the VAS scale on day 3 was statistically significantly different from that on day 8 (6.227 ± 0.146 vs. 4.864 ± 0.190; p = 0.0001). Conclusions. KT is an effective method for improving subcutaneous drainage and decreasing subcutaneous tissue. However, KT does not affect postoperative pain and ROM. Full article

Background: the Videofluoroscopic Dysphagia Scale (VDS) is used to interpret and predict the long-term prognosis of patients with dysphagia. However, the inter-rater agreement of the VDS was shown to be lower in a previous study. To overcome the mentioned limitation of the VDS, a modified version (mVDS) was created and applied clinically. We aimed to validate its usefulness in determining the appropriate feeding method and predicting the prognosis of dysphagia. Methods: the videofluroscopic swallowing study (VFSS) data of 50 patients with dysphagia were collected retrospectively. The VFSS data were evaluated using the mVDS, and the inter-rater reliability was calculated. We also evaluated the association between the mVDS and type of feeding method selected, and between the mVDS and presence of aspiration pneumonia in patients with dysphagia. Results: among the different parameters of mVDS, “aspiration” showed the highest reliability (k = 0.767), followed by “mastication” and “lip closure” (k = 0.648 and k = 0.634, respectively). Conversely, “triggering pharyngeal swallow” and “pyriformis residue” demonstrated the lowest reliabilities (k = 0.312 and k = 0.324, respectively). The intraclass correlation coefficient (ICC), which is used as a measure of the reliability of the total mVDS score, was 0.876. In all patients with dysphagia, the mVDS score correlated significantly with the type of feeding method selected (p < 0.05), and the presence of aspiration pneumonia (p < 0.05). Conclusion: the ICC of the total mVDS score was 0.876. Therefore, the mVDS could be a useful tool for quantifying the severity of dysphagia. It could be helpful in the analysis of the VFSS findings among patients with dysphagia in clinical settings and research. Full article

The innovative Eye Movement Modelling Examples (EMMEs) method can be used in medicine as an educational training tool for the assessment and verification of students and professionals. Our work was intended to analyse the possibility of using eye tracking tools to verify the skills and training of people engaged in laboratory medicine on the example of parasitological diagnostics. Professionally active laboratory diagnosticians working in a multi-profile laboratory (non-parasitological) (n = 16), laboratory diagnosticians no longer working in this profession (n = 10), and medical analyst students (n = 56), participated in the study. The studied group analysed microscopic images of parasitological preparations made with the cellSens Dimension Software (Olympus) system. Eye activity parameters were obtained using a stationary, video-based eye tracker Tobii TX300 which has a 3-ms temporal resolution. Eye movement activity parameters were analysed along with time parameters. The results of our studies have shown that the eye tracking method is a valuable tool for the analysis of parasitological preparations. Detailed quantitative and qualitative analysis confirmed that the EMMEs method may facilitate learning of the correct microscopic image scanning path. The analysis of the results of our studies allows us to conclude that the EMMEs method may be a valuable tool in the preparation of teaching materials in virtual microscopy. These teaching materials generated with the use of eye tracking, prepared by experienced professionals in the field of laboratory medicine, can be used during various training, simulations and courses in medical parasitology and contribute to the verification of education results, professional skills, and elimination of errors in parasitological diagnostics. Full article

It is yet unknown whether the intravenous administration route alone can fully account for the exacerbation of medication-related osteonecrosis of the jaw (MRONJ). The purpose of this retrospective study was to identify the potential role of the bisphosphonate (BP) administration route as an independent prognostic factor for non-cancerous, stage III MRONJ patients. Bone samples were retrospectively obtained from two groups of osteoporosis patients who underwent surgery for the treatment of stage III MRONJ. Among the subjects, 10 had a history of only oral BP consumption and 10 of intravenous (IV) BP administration. The samples were assessed for osteoclast morphology and immunohistochemical expression of the receptor activator of NF-κB ligand (RANKL), osteoprotegerin (OPG), and potassium calcium-activated channel subfamily N member 4 (Kcnn4). Although the osteoclasts derived from both groups exhibited no significant differences in the mean quantity, diameter, and nuclearity, significantly attenuated tartrate-resistant acid phosphatase activity was noted among the IV BP-induced MRONJ bones compared to those of the oral BP group. Significant suppression of the RANKL/OPG ratio and Kcnn4 expression among the retrieved bones of IV BP group patients was also noted. Our results indicate the potential of the BP administration route as an independent prognostic factor for advanced-stage MRONJ, regardless of the dosage or indication for which the BP was prescribed. Full article

Background: The dose of citrate needed in regional citrate anticoagulation (RCA) to achieve optimal biocompatibility is unknown. We performed a randomized trial comparing two doses (ACTRN12613001340729). Methods: In 30 patients a single hemodialysis with either standard (2.7 mmol/L) or increased dose of citrate (4 mmol/L) was performed. C5a-desArg, myeloperoxidase (MPO), thrombin-antithrombin complex (TAT), and platelet factor 4 (PF4) were measured and the inner surface of the dialyzer fibers was evaluated with scanning electron microscopy (SEM). Results: A good separation of anticoagulation effect was achieved (post-filter ionized calcium 0.20 vs. 0.31 mmol/L, p < 0.05). There was no effect of citrate dose on any of the biocompatibility parameters; transient and parallel increase in PF4 after 30 min and parallel increase in TAT after 4 h were observed. There were no visually detected clotting problems within the circuit and no significant hypocalcemia in either group. SEM clotting score was excellent and comparable in both groups (p = 0.59). Conclusions: Given the excellent results in both groups, absence of between group differences and inability of the increased dose of citrate to completely blunt the small residual increase in PF4 and TAT, we conclude that the standard dose of citrate seems sufficient in RCA for chronic hemodialysis. Full article

Background: Acute tubulointerstitial nephritis (ATIN) diagnosis lays on histological assessment through a kidney biopsy, given the absence of accurate non-invasive biomarkers. The aim of this study was to evaluate the accuracy of different urinary inflammation-related cytokines for the diagnostic of ATIN and its distinction from acute tubular necrosis (ATN). Methods: We included 33 patients (ATIN (n = 21), ATN (n = 12)), and 6 healthy controls (HC). We determined the urinary levels of 10 inflammation-related cytokines using a multiplex bead-based Luminex assay at the time of biopsy and after therapy, and registered main clinical, analytical and histological data. Results: At the time of biopsy, urinary levels of I-TAC/CXCL11, CXCL10, IL-6, TNFα and MCP-1 were significantly higher in ATIN compared to HC. A positive correlation between the extent of the tubulointerstitial cellular infiltrates in kidney biopsies and the urinary concentration of I-TAC/CXCL11, MIG/CXCL9, CXCL10, IL17, IFNα, MCP1 and EGF was observed. Notably, I-TAC/CXCL11, IL-6 and MCP-1 were significantly higher in ATIN than in ATN, with I-TAC/CXCL11 as the best discriminative classifier AUC (0.77, 95% CI 0.57–0.95, p = 0.02). A combinatory model of these three urinary cytokines increased the accuracy in the distinction of ATIN/ATN compared to the individual biomarkers. The best model resulted when combining the three cytokines with blood eosinophil and urinary leukocyte counts (LR = 9.76). Follow-up samples from 11ATIN patients showed a significant decrease in I-TAC/CXCL11, MIG/CXCL9 and CXCL10 levels. Conclusions: Urinary I-TAC/CXCL11, CXCL10, IL6 and MCP-1 levels accurately distinguish patients developing ATIN from ATN and healthy individuals and may serve as novel non-invasive biomarkers in this disease. Full article

Objectives: Subcutaneous emphysema (SCE) is a complication associated with laparoscopic surgery. Severe SCE complicated by excessive hypercarbia may afford detrimental effects in surgical patients with cardiac dysfunction. Robotic-assisted laparoscopic radical prostatectomy (RALP) has several predisposing factors that contribute to SCE. The main purpose of our single-center retrospective study was to determine the preoperative and intraoperative predicting factors for SCE associated with RALP and to determine the actual incidence of SCE. Methods: In total, 229 adult male patients underwent standardized RALP for prostate cancer over the period of 1 May 2016 to 31 October 2018 at the Ehime University Hospital. We reviewed electronic clinical records for individual characteristics including age, body weight, height, coexisting disorders, preoperative ASA physical status, and the length of postoperative hospital stay. We also reviewed surgical and anesthetic records for the operation time, anesthetic method, and the partial pressure of end-tidal CO₂ (PetCO₂) during RALP. To determine the presence of SCE, we examined supine chest X-rays obtained after the completion of surgery. Results: We found 55 cases (24.0%) of SCE. Multiple logistic regression analysis showed that a BMI < 25 kg/m² (OR: 3.0, 95% CI: 1.25–7.26) and a maximum value of PetCO₂ of 46 mmHg or greater (OR: 23.3, 95% CI: 8.22–66.1) were independent predicting factors for SCE. Conclusion: These two predicting factors may be helpful to recognize the occurrence of SCE. Anesthesiologists should protect against SCE progression with the earlier detection of SCE for safe anesthetic management in patients undergoing RALP. Full article

Small-for-gestational-age (SGA) infants have been associated with increased risk of adverse perinatal outcomes (APOs). In this work, we assess the predictive ability of the ultrasound-estimated percentile weight (EPW) at 35 weeks of gestational age to predict late-onset SGA and APOs, according to six growth standards, and whether the ultrasound–delivery interval influences the detection rate. To this purpose, we analyze a retrospective cohort study of 9585 singleton pregnancies. EPWs at 35 weeks were calculated to the customized Miguel Servet University Hospital (MSUH) and Figueras standards and the non-customized MSUH, Fetal Medicine Foundation (FMF), INTERGROWTH-21st, and WHO standards. As results of our analysis, for a 10% false positive rate, the detection rates for SGA ranged between 48.9% with the customized Figueras standard (AUC 0.82) and 60.8% with the non-customized FMF standard (AUC 0.87). Detection rates to predict SGA by ultrasound–delivery interval (1–6 weeks) show higher detection rates as intervals decrease. APOs detection rates ranged from 27.0% with FMF to 7.9% with the Figueras standard. In conclusion, the ability of EPW to predict SGA at 35 weeks is good for all standards, and slightly better for non-customized standards. The APO detection rate is significantly greater for non-customized standards. Full article

Objectives: This study aimed at investigating the prognostic impact of tumor necrosis and preoperative monocyte-to-lymphocyte ratio (MLR) in patients treated with radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). Methods: A total of 521 patients with UTUC treated with RNU from January 2008 to June 2019 at our institution were enrolled. Histological tumor necrosis was defined as the presence of microscopic coagulative necrosis. The optimal value of MLR was determined as 0.4 by receiver operating characteristic (ROC) analysis based on cancer-specific mortality. The Kaplan–Meier method with log-rank test and Cox proportional hazards regression models were performed to evaluate the impact of tumor necrosis and MLR on overall (OS), cancer-specific (CSS), and recurrence-free survival (RFS). Furthermore, ROC analysis was used to estimate the predictive ability of potential prognostic factors for oncological outcomes. Results: Tumor necrosis was present in 106 patients (20%), which was significantly associated with tumor location, high pathological tumor stage, lymph node metastasis, high tumor grade, lymphovascular invasion, tumor size, and increased monocyte counts. On multivariate analysis, the combination of tumor necrosis and preoperative MLR was an independent prognosticator of OS, CSS, and RFS (all p < 0.05). Moreover, ROC analyses revealed the predictive accuracy of a combination of tumor necrosis and preoperative MLR for OS, CSS, and RFS with the area under the ROC curve of 0.745, 0.810, and 0.782, respectively (all p < 0.001). Conclusions: The combination of tumor necrosis and preoperative MLR can be used as an independent prognosticator in patients with UTUC after RNU. The identification of this combination could help physicians to recognize high-risk patients with unfavorable outcomes and devise more appropriate postoperative treatment plans. Full article

Background: The recommendations for routine preoperative esophagogastroduodenoscopy (EGD) in patients qualified for bariatric surgeries are still a matter of debate. The aim of this study was to analyze the pathologies on preoperative EGD in patients qualified for bariatric surgeries. Materials and Methods: This study included 222 patients, divided into two groups. The obesity group consisted of patients with obesity (BMI ≥ 40 kg/m²), for whom EGD was a routine part of the preparation for laparoscopic sleeve gastrectomy (LSG). The control group of patients with normal body weight (BMI) qualified for EGD because of gastrointestinal ailments. Results: Regarding preoperative EGD in patients qualified for bariatric surgeries, we analyzed the prevalence of endoscopic pathologies in various gastrointestinal tract segments. Patients with obesity were shown to present with esophageal pathologies significantly more often than persons in the control group (n = 23, 20.91% vs. n = 12, 10.91%, p = 0.042). The odds ratio of esophageal pathologies in patients with obesity versus the control group equaled 2.15 (95%CI: 1.01–4.59). In turn, the odds ratio of duodenal pathologies in patients from the control group was 3.31 (95%Cl: 1.16–9.47), which means that persons from this group were approximately three times more likely to be diagnosed with those pathologies compared to obese patients. Moreover, patient sex was a significant predictor of duodenal pathologies, with an odds ratio of 4.03 (95%CI: 1.53–10.61). Conclusions: Preoperative EGD can identify a broad spectrum of pathologies in obese patients, which suggests a routine examination before bariatric surgery. Full article

Transcranial direct current stimulation (tDCS) is a non-invasive, easy to administer, well-tolerated, and safe technique capable of affecting brain excitability, both at the cortical and cerebellum levels. However, its effectiveness has not been sufficiently assessed in all population segments or clinical applications. This systematic review aimed at compiling and summarizing the currently available scientific evidence about the effect of tDCS on functionality in older adults over 60 years of age. A search of databases was conducted to find randomized clinical trials that applied tDCS versus sham stimulation in the above-mentioned population. No limits were established in terms of date of publication. A total of 237 trials were found, of which 24 met the inclusion criteria. Finally, nine studies were analyzed, including 260 healthy subjects with average age between 61.0 and 85.8 years. Seven of the nine included studies reported superior improvements in functionality variables following the application of tDCS compared to sham stimulation. Anodal tDCS applied over the motor cortex may be an effective technique for improving balance and posture control in healthy older adults. However, further high-quality randomized controlled trials are required to determine the most effective protocols and to clarify potential benefits for older adults. Full article

Background. The pathogenesis of chronic spontaneous urticaria involves metabolic, immunological, and psychological factors. The thiol–disulfide exchange reactions could be a mechanism to counteract oxidative stress in patients with chronic spontaneous urticaria. Objective: The assessment of thiol–disulfide homeostasis parameters (TDHPs) according to disease severity and the influence of H1-antihistamine therapy in patients with chronic spontaneous urticaria. Material and method. We have included 30 patients with chronic spontaneous urticaria in the study and we have determined the levels of native thiol, total thiol, disulfides as well as the disulfide/native thiol ratio, disulfide/total thiol ratio and the native thiol/total thiol ratio, before and after therapy with H1-antihistamines. Results. The results of the study showed altered levels of TDHPs and their normalization after treatment with H1-antihistamines in patients with chronic spontaneous urticaria. We determined a statistically significant increase in the serum levels of total thiol, native thiol, and native thiol/total thiol ratio and a significant reduction in the levels of disulfides, disulfide/native thiol ratio and disulfide/total thiol ratio after treatment with H1-antihistamines. The normalization of the serum levels of TDHPs has been associated with the relief of symptoms and reduction or resolution of pruritus and urticarial plaques. Conclusion. These results suggest the involvement of thiol–disulfide homeostasis in the defense against the harmful effects of reactive oxygen species in patients with chronic spontaneous urticaria and the potential role of TDHPs in monitoring H1-antihistamine therapy. To the best of our knowledge, this is the first study investigating TDHPs in patients with chronic spontaneous urticaria before and after treatment. Full article

Aims: The CARTOFINDER module allows for simultaneous and automated detection of repetitive focal and rotational activations in patients with atrial arrhythmias. This study aimed to validate the CARTOFINDER algorithm for the detection of potential drivers for atrial fibrillation (AF) and to access their potential impact on individual arrhythmia substrates. Methods: Fifty consecutive patients underwent AF ablation for persistent AF (PERS), using a 3D-mapping system with the integrated CARTOFINDER module. Regions of interest (ROIs) were identified before and after ablation, and their spatial and temporal relationship was correlated with areas of fibrosis. Results: Procedural success was achieved in all patients and 42% received ablation beyond pulmonary vein isolation (PVI). AF termination was observed in 6 patients (12%). The mean procedure duration was 134 ± 29 min. ROIs were revealed in all patients (mean n = 77 ± 52) and there was no statistical evidence for a predilection site. There was no significant anatomical correlation between ROIs and bipolar low voltage. Remapping confirmed the elimination of ROIs in relation to the individual ablation site, a limited reproducibility of rotational ROIs and persistent focal activity over time in some anatomical segments. ROIs were not a predictor for AF recurrence during following ablation. Conclusions: CARTOFINDER mapping can be integrated into a routine workflow for AF ablation. ROIs could be discriminated in all patients and an ablation effect was observed in some patients, whereas persistent activity was found in certain anatomical segments, even after ablation. ROIs might be an additional ablation target when we are able to understand the individual substrate. Full article

Background: Randomized controlled trials have reported excess mortality in patients treated with paclitaxel-coated devices versus uncoated devices, while observational studies have reported the opposite. This study aims to determine the underlying factors and cohort differences that may explain these opposite results, with specific focus on sex differences in treatment and outcomes. Methods: Multicenter health insurance claims data from a large insurance fund, BARMER, were studied. A homogeneous sample of patients with an index of endovascular revascularization for symptomatic peripheral arterial occlusive disease between 2013 and 2017 was included. Adjusted logistic regression and Cox regression models were used to determine the factors predicting allocation to paclitaxel-coated devices and sex-specific 5-year all-cause mortality, respectively. Results: In total, 13,204 patients (54% females, mean age 74 ± 11 years) were followed for a median of 3.5 years. Females were older (77 vs. 71 years), and had less frequent coronary artery disease (23% vs. 33%), dyslipidemia (44% vs. 50%), and diabetes (29% vs. 41%), as well as being less likely to have a history of smoking (10% vs. 15%) compared with males. Mortality differences were mostly attributable to the female subgroup who were revascularized above the knee (hazard ratio, HR 0.78, 95% CI: 0.64–0.95), while no statistically significant differences were observed in males. Conclusions: This study found that females treated above the knee benefited from paclitaxel-coated devices, while no differences were found in males. Ongoing and future registries and trials should take sex disparities into account. Full article

To investigate the expression of vascular endothelial growth factor (VEGF)-C and vascular endothelial growth factor receptor (VEGFR)3 in the trabecular meshwork (TM) of patients with glaucoma and cultured TM cells. Methods: The expressions of VEGF-C in angle tissues collected by trabeculectomy from patients with glaucoma and non-glaucomatous choroidal malignant melanoma were analyzed by immunohistochemistry. Additionally, VEGF-C concentrations were determined in the aqueous humor of patients with glaucoma by ELISA. The expressions of VEGFR3, which is a receptor of VEGF-C in cultured TM cells, were analyzed by Western blot analysis and immunocytochemistry. Cultured TM cells were stimulated by oxidative stress, hypoxia, or high glucose conditions, and VEGF-C concentrations in supernatants and cell lysates were determined by ELISA. Results: VEGF-C immunoreactivity was positive in TM tissues of glaucoma patients, but not in those of non-glaucomatous controls. VEGF-C concentrations in the aqueous humor of patients with neovascular glaucoma and primary open-angle glaucoma were lower than those with non-glaucoma patients. VEGFR3 was expressed in cultured TM cells. VEGF-C concentrations in supernatants or cell lysates of TM cells cultured under oxidative stress and hypoxia were significantly elevated compared with those under steady conditions (p < 0.05). VEGF-C concentrations in supernatants and cell lysates of TM cells cultured in high glucose were significantly higher than those in low glucose (p < 0.01). Conclusions: VEGF-C was expressed in TM tissues of patients with glaucoma, which was secreted from cultured TM cells under various pathological conditions. These results suggest that VEGF-C may be involved in the pathology of glaucoma. Full article

We aimed to evaluate the functional and radiographic outcomes of a three-dimensionally (3D) pre-contoured lateral locking plate fixation for isolated Weber B type fractures and to evaluate the necessity of an interfragmentary lag screw in the use of the plate. Patients who underwent surgery for isolated Weber B type fracture were divided into two groups: 41 patients treated with the 3D plate and lag screw (Group A) and 31 patients treated with the 3D plate only (Group B). The included patients were evaluated regarding the functional and radiographic outcomes. According to the McLennan and Ungersma criteria, the majority of patients showed good or fair outcomes in both groups. Comparing the two groups, Group B showed better functional outcomes (p < 0.0046), while no difference between the two groups was found in terms of the radiographic outcomes (p = 0.143). The operation time was significantly shorter in Group B (p < 0.001) and the time to bony union was within 14 months in all patients with no significant difference between the two groups (p = 0.0821). No postoperative complication was observed in both groups. In conclusion, the use of a 3D pre-contoured lateral locking plate fixation for isolated Weber B type fractures demonstrated satisfactory functional and radiographic outcomes, regardless of lag screw insertion. Full article

Repetitive transcranial magnetic stimulation (rTMS) may support motor function recovery in patients with incomplete spinal cord injury (iSCI). Its effectiveness mainly depends on the applied algorithm. This clinical and neurophysiological study aimed to assess the effectiveness of high-frequency rTMS in iSCI patients at the C2–Th12 levels. rTMS sessions (lasting 3–5 per month, from 2 to 11 months, 5 months on average) were applied to 26 iSCI subjects. The motor cortex was bilaterally stimulated with a frequency at 20–25 Hz and a stimulus strength that was 70–80% of the resting motor threshold (15.4–45.5% maximal output) during one therapeutic session. Surface electromyography (sEMG) recordings at rest and during maximal contractions and motor evoked potential (MEP) recordings were performed from the abductor pollicis brevis (APB) and the tibialis anterior (TA) muscles. The same neurophysiological studies were also performed in patients treated with kinesiotherapy only (K group, n = 25) and compared with patients treated with both kinesiotherapy and rTMS (K + rTMS). A decrease in sEMG amplitudes recorded at rest from the APB muscles (p = 0.001) and an increase in sEMG amplitudes during the maximal contraction of the APB (p = 0.001) and TA (p = 0.009) muscles were found in the K + rTMS group. A comparison of data from MEP studies recorded from both APB and TA muscles showed significant changes in the mean amplitudes but not in latencies, suggesting a slight improvement in the transmission of spinal efferent pathways from the motor cortex to the lower spinal centers. The application of rTMS at 20–25 Hz reduced spasticity in the upper extremity muscles, improved the recruitment of motor units in the upper and lower extremity muscles, and slightly improved the transmission of efferent neural impulses within the spinal pathways in patients with C2–Th12 iSCI. Neurophysiological recordings produced significantly better parameters in the K + rTMS group of patients after therapy. These results may support the hypothesis about the importance of rTMS therapy and possible involvement of the residual efferent pathways including propriospinal neurons in the recovery of the motor control of iSCI patients. Full article

Delirium is a sign of deterioration of homeostasis and worse prognosis. The aim of this study was to investigate the frequency, risk factors and prognosis of delirium in patients with COVID-19 in a temporary acute setting hospital. A retrospective cohort analysis of data collected between October 2020 and February 2021 from two temporary acute care hospitals was performed. All consecutive hospitalized patients ≥18 years old with COVID-19 were included. An assessment of consciousness was carried out at least two times a day, including neurological examination. Delirium was identified through retrospective chart review according to DSM-5 criteria if present at least once during hospitalization. Analysis included 201 patients, 39 diagnosed with delirium (19.4%). Delirious patients were older (p < 0.001), frailer (p < 0.001) and the majority were male (p = 0.002). Respiratory parameters were worse in this group with higher oxygen flow (p = 0.013), lower PaO₂ (p = 0.043) and higher FiO₂ (p = 0.006). The mortality rate was significantly higher in patients with delirium (46.15% vs 3.70%, p < 0.001) with OR 17.212 (p < 0.001) corrected for age and gender. Delirious patients experienced significantly more complications: cardiovascular (OR 7.72, p < 0.001), pulmonary (OR 8.79, p < 0.001) or septic (OR 3.99, p = 0.029). The odds of mortality in patients with COVID-19 presenting with delirium at any point of hospitalization were seventeen times higher. Full article

The aim of this study was to evaluate the potential anti-angiogenic effect of MTRN (meteorin) in the laser-induced CNV rat model and explore its mechanisms of action. MTRN, thrompospondin-1, glial cell markers (GFAP, vimentin), and phalloidin were immuno-stained in non-human primate flat-mounted retinas and human retina cross sections. The effect of MTRN at different doses and time points was evaluated on laser-induced CNV at 14 days using in vivo fluorescein angiography and ex vivo quantification of CNV. A pan transcriptomic analysis of the retina and the RPE/choroid complex was used to explore MTRN effects mechanisms. In human retina, MTRN is enriched in the macula, expressed in and secreted by glial cells, and located in photoreceptor cells, including in nuclear bodies. Intravitreal MTRN administered preventively reduced CNV angiographic scores and CNV size in a dose-dependent manner. The highest dose, administered at day 7, also reduced CNV. MTRN, which is regulated by mineralocorticoid receptor modulators in the rat retina, regulates pathways associated with angiogenesis, oxidative stress, and neuroprotection. MTRN is a potential novel therapeutic candidate protein for wet AMD. Full article