J. Clin. Med., Volume 10, Issue 2 (January-2 2021) – 207 articles

Background: Postoperative pain after video-assisted thoracoscopic surgery (VATS) affects patients’ recovery, postoperative complications, and length of stay (LOS). Despite its relevance, there are no guidelines on optimal perioperative pain management. This study aims to analyse the effects of an additional intercostal catheter (ICC) in comparison to a single shot intraoperative intercostal nerve block (SSINB). Methods: All patients receiving an anatomic VATS resection between June 2019 and May 2020 were analysed retrospectively. The ICC cohort included 51 patients, the SSINB cohort included 44 patients. Results: There was no difference in age, gender, comorbidities, or duration of surgery between cohorts. Pain scores on the first postoperative day, after chest drain removal, and highest pain score measured did not differ between groups. The overall amount of opioids (morphine equivalent: 3.034 mg vs. 7.727 mg; p = 0.002) as well as the duration of opioid usage (0.59 days vs. 1.25 days; p = 0.005) was significantly less in the ICC cohort. There was no difference in chest drain duration, postoperative complications, and postoperative LOS. Conclusions: Pain management with ICC reduces the amount of opioids and number of days with opioids patients require to achieve sufficient analgesia. In conclusion, ICC is an effective regional anaesthesia tool in postoperative pain management in minimally invasive thoracic surgery. Full article

Diabetic foot ulcers, complicated by osteomyelitis, can be treated by surgical resection, dead space filling with gentamicin-loaded calcium sulphate-hydroxyapatite (CaS-HA) biocomposite, and closure of soft tissues and skin. To assess the feasibility of this treatment regimen, we conducted a multicenter retrospective cohort study of patients after failed conventional treatments. From 13 hospitals we included 64 patients with forefoot (n = 41 (64%)), midfoot (n = 14 (22%)), or hindfoot (n = 9 (14%)) ulcers complicated by osteomyelitis. Median follow-up was 43 (interquartile range, 20–61) weeks. We observed wound healing in 54 patients (84%) and treatment success (wound healing without ulcer recurrence) in 42 patients (66%). Treatment failures (no wound healing or ulcer recurrence) led to minor amputations in four patients (6%) and major amputations in seven patients (11%). Factors associated with treatment failures in univariable Cox regression analysis were gentamicin-resistant osteomyelitis (hazard ratio (HR), 3.847; 95%-confidence interval (CI), 1.065–13.899), hindfoot ulcers (HR, 3.624; 95%-CI, 1.187–11.060) and surgical procedures with gentamicin-loaded CaS-HA biocomposite that involved minor amputations (HR, 3.965; 95%-CI, 1.608–9.777). In this study of patients with diabetic foot ulcers, complicated by osteomyelitis, surgical treatment with gentamicin-loaded CaS-HA biocomposite was feasible and successful in 66% of patients. A prospective trial of this treatment regimen, based on a uniform treatment protocol, is required. Full article

The important prevalence of autoimmune thyroid disease (AITD) in the general population was the main motivation for conducting the present study. The present paper aims to estimate the possible comorbidities related to female sexual dysfunction (FSD) and depression related to AITD. The study group consisted of 320 patients: 250 cases known with untreated AITD, divided into subgroups (euthyroid subgroup, subclinical hypothyroidism subgroup and clinical hypothyroidism subgroup); respectively 70 healthy females in the control group. Patients underwent thyroid evaluation, ovarian evaluation and laboratory assays. At the time of the diagnosis of autoimmune thyroid disease, psychometric scales were filled in by the patients: the Female Sexual Function Index 6 (FSFI-6) and the Beck’s Depression Inventory-II (BDI-II). It was observed that healthy patients had significantly higher FSFI scores than patients with AITD (28 vs. 27; p = 0.006). In the AITD group, the risk of FSD increases with the severity of thyroid disease. The most affected areas were: sexual desire (p < 0.001), lubrication (p = 0.001) and orgasm (p = 0.008), followed by excitability and sexual satisfaction. The severity of hypothyroidism influences the degree of decrease in libido, central and peripheral excitability. Sexual satisfaction and orgasm were less influenced. The field related to pain seems uninfluenced by the presence of thyroid disease. The concomitant presence of depression and the value of thyroid-stimulating hormone (TSH) are risk factors in the development of FSD. Higher TSH value and BDI-II score increase the risk of female sexual dysfunction by 1.083 and 1.295 times, respectively. Our findings are significant and promising; they may help professionals dealing with sexual and reproductive health. Despite the importance of female sexual dysfunction and its prevalence, clinicians and patients often ignore it. In fact, only a small percentage of patients consult their doctors about sexual health, and their doctors do not often ask them questions related to this aspect. Full article

High tibial osteotomy (HTO) and knee joint distraction (KJD) are joint-preserving treatments that unload the more affected compartment (MAC) in knee osteoarthritis. This post-hoc study compares two-year cartilage-thickness changes after treatment with KJD vs. HTO, and identifies factors predicting cartilage restoration. Patients indicated for HTO were randomized to KJD (KJD_HTO) or HTO treatment. Patients indicated for total knee arthroplasty received KJD (KJD_TKA). Outcomes were the MRI mean MAC cartilage thickness and percentage of denuded bone area (dABp) change two years after treatment, using radiographic joint space width (JSW) as the reference. Cohen’s d was used for between-group effect sizes. Post-treatment, KJD_HTO patients (n = 18) did not show significant changes. HTO patients (n = 33) displayed a decrease in MAC cartilage thickness and an increase in dABp, but an increase in JSW. KJD_TKA (n = 18) showed an increase in MAC cartilage thickness and JSW, and a decrease in dABp. Osteoarthritis severity was the strongest predictor of cartilage restoration. Kellgren–Lawrence grade ≥3 showed significant restoration (p < 0.01) after KJD; grade ≤2 did not. Effect sizes between severe KJD and HTO patients were large for MAC MRI cartilage thickness (d = 1.09; p = 0.005) and dABp (d = 1.13; p = 0.003), but not radiographic JSW (d = 0.28; p = 0.521). This suggests that in knee osteoarthritis patients with high disease severity, KJD may be more efficient in restoring cartilage thickness. Full article

This study aims to investigate the two-year clinical outcomes between first-generation (1G) and second-generation (2G) drug-eluting stents (DES) based on pre-percutaneous coronary intervention (PCI) thrombolysis in myocardial infarction (TIMI) flow grade (pre-TIMI) in patients with ST-segment elevation myocardial infarction (STEMI). Overall, 17,891 STEMI patients were classified into two groups: pre-TIMI 0/1 group (n = 12,862; 1G-DES (n = 4318), 2G-DES (n = 8544)) and pre-TIMI 2/3 group (n = 5029; 1G-DES (n = 2046), 2G-DES (n = 2983)). During a two-year follow-up period, major adverse cardiac events (MACEs) defined as all-cause death, recurrent myocardial infarction (re-MI), or any repeat revascularization and stent thrombosis (ST) were considered as the primary and the secondary outcomes. In the pre-TIMI 0/1 and 2/3 groups, the cumulative incidences of MACEs (adjusted hazard ratio (aHR): 1.348, p < 0.001, and aHR: 1.415, p = 0.02, respectively) and any repeat revascularization (aHR: 1.938, p < 0.001, and aHR: 1.674, p = 0.001, respectively) were significantly higher in the 1G-DES than in the 2G-DES. However, sirolimus-eluting stent showed similar cumulative incidence of any repeat revascularization compared with zotarolimus-eluting stent and biolimus-eluting stent in both pre-TIMI 0/1 and 2/3 groups. The cumulative incidences of all-cause death, re-MI, and ST were similar between the 1G-DES and 2G-DES groups. In this study, 2G-DES showed better clinical outcomes than 1G-DES concerning MACEs and any repeat revascularization regardless of pre-TIMI. However, more research is needed to support these results. Full article

Chromodomain Helicase DNA-binding 8 (CHD8) is a high confidence risk factor for autism spectrum disorders (ASDs) and the genetic cause of a distinct neurodevelopmental syndrome with the core symptoms of autism, macrocephaly, and facial dysmorphism. The role of CHD8 is well-characterized at the structural, biochemical, and transcriptional level. By contrast, much less is understood regarding how mutations in CHD8 underpin altered brain function and mental disease. Studies on various model organisms have been proven critical to tackle this challenge. Here, we scrutinize recent advances in this field with a focus on phenotypes in transgenic animal models and highlight key findings on neurodevelopment, neuronal connectivity, neurotransmission, synaptic and homeostatic plasticity, and habituation. Against this backdrop, we further discuss how to improve future animal studies, both in terms of technical issues and with respect to the sex-specific effects of Chd8 mutations for neuronal and higher-systems level function. We also consider outstanding questions in the field including ‘humanized’ mice models, therapeutic interventions, and how the use of pluripotent stem cell-derived cerebral organoids might help to address differences in neurodevelopment trajectories between model organisms and humans. Full article

Autoimmune thrombotic thrombocytopenic purpura (iTTP) is a life-threatening, relapsing disease in which an acquired deficiency of the enzyme ADAMTS13 leads to generalised microvascular thrombosis. Survivors have a high prevalence of depression and impaired cognitive function. The aim of this study was to determine whether life circumstances and personality have an influence on the development and severity of depression and anxiety in iTTP patients and how they impact the quality of life. With validated questionnaires, we examined the prevalence of depression and anxiety symptoms in 104 iTTP patients, as well as parameters of subjective cognitive deficits, quality of life, attitude to life and resilience. iTTP patients had significantly more depressive symptoms (p < 0.001), a tendency to have anxiety disorders (p = 0.035) and a significantly worse cognitive performance (p = 0.008) compared to the controls. Sex, age, physical activity and partnership status had no significant influence on depression, whereas the number of comorbidities did. Lower scores of resilience, attitude to life and quality of life were reported by patients compared to controls. iTTP patients had a high prevalence of depression and anxiety, as well as a more negative attitude to life and low resilience. Resilience correlated negatively with the severity of the depression. Furthermore, quality of life and cognitive performance were significantly reduced. Full article

Inflammatory bowel diseases (IBDs) may be associated with extra-intestinal manifestations. Among these, mucocutaneous manifestations are relatively frequent, often difficult to diagnose and treat, and may complicate the course of the underlying disease. In the present review, a summary of the most relevant literature on the dermatologic manifestations occurring in patients with inflammatory bowel diseases has been reviewed. The following dermatological manifestations associated with IBDs have been identified: (i) specific manifestations with the same histological features of the underlying IBD (occurring only in Crohn’s disease); (ii) cutaneous disorders associated with IBDs (such as aphthous stomatitis, erythema nodosum, psoriasis, epidermolysis bullosa acquisita); (iii) reactive mucocutaneous manifestations of IBDs (such as pyoderma gangrenosum, Sweet’s syndrome, bowel-associated dermatosis-arthritis syndrome, aseptic abscess ulcers, pyodermatitis–pyostomatitis vegetans, etc.); (iv) mucocutaneous conditions secondary to treatment (including injection site reactions, infusion reactions, paradoxical reactions, eczematous and psoriasis-like reactions, cutaneous infections, and cutaneous malignancies); (v) manifestations due to nutritional malabsorption (such as stomatitis, glossitis, angular cheilitis, pellagra, scurvy, purpura, acrodermatitis enteropathica, phrynoderma, seborrheic-type dermatitis, hair and nail abnormalities). An accurate dermatological examination is essential in all IBD patients, especially in candidates to biologic therapies, in whom drug-induced cutaneous reactions may assume marked clinical relevance. Full article

Immunoglobin A (IgA) nephropathy causes chronic kidney disease worldwide. Therefore, identifying risk factors associated with the progression of IgA nephropathy is crucial. Anemia is a common complication of chronic kidney disease; however, few studies have investigated the effect of serum hemoglobin on the renal prognosis of IgA nephropathy. This study aimed to determine the effect of serum hemoglobin on the progression of IgA nephropathy. We retrospectively analyzed 4326 patients with biopsy-proven IgA nephropathy. We evaluated the effect of serum hemoglobin on IgA nephropathy progression using Kaplan–Meier survival analyses, the log-rank test, and the Cox proportional hazards model. The primary end-point was progression of IgA nephropathy, defined as dialysis initiation or kidney transplantation. Serum hemoglobin showed a nonlinear relationship with the progression of IgA nephropathy. The Cox proportional hazards model showed that the risk of progression of IgA nephropathy decreased 0.87 times for every 1.0 g/dL increase in serum hemoglobin. In subgroup analyses, reduced serum hemoglobin was an independent risk factor for IgA nephropathy progression only in women. There was no statistically significant interaction of serum hemoglobin between men and women (P_interaction = 0.177). Results of Sensitivity analysis were robust and consistent. Serum hemoglobin at diagnosis was an independent predictor for IgA nephropathy progression. Full article

Non-controlled hemorrhage with accompanying trauma-induced coagulopathy (TIC) remains the most common cause of preventable death after multiple injury. Rapid identification followed by aggressive treatment is the key for improved outcomes. Treatment of trauma hemorrhage begins at the scene, with manual compression, the use of tourniquets and (non) commercial pelvic slings, and rapid transfer to an adequate trauma center. Upon hospital admission, coagulation monitoring and support are to be initiated immediately. Bleeding is controlled surgically following damage control principles. Modern coagulation management includes goal-oriented, individualized therapies, guided by point-of-care viscoelastic assays. Idarucizumab can be used as an antidote to the thrombin inhibitor dabigatran, andexanet alpha as an antidote to factor Xa inhibitors. This review summarizes the key recommendations of the 2019 updated European guideline on the management of major bleeding and coagulopathy following trauma. These evidence-based recommendations may form the backbone of algorithms adapted to local logistics and infrastructure. Full article

Background: Post-transplant lymphoproliferative disorder (PTLD) is a complication of organ transplantation classified according to the WHO as nondestructive, polymorphic, monomorphic, and classic Hodgkin Lymphoma subtypes. In this retrospective study, we investigated the potential of semi-quantitative 2-[¹⁸F]fluoro-2-deoxy-D-glucose ([¹⁸F]FDG) PET/computed tomography (CT)-based parameters to differentiate between the PTLD morphological subtypes. Methods: 96 patients with histopathologically confirmed PTLD and baseline [¹⁸F]FDG PET/CT between 2009 and 2019 were included. Extracted semi-quantitative measurements included: Maximum, peak, and mean standardized uptake value (SUV_max, SUV_peak, and SUV_mean). Results: Median SUVs were highest for monomorphic PTLD followed by polymorphic and nondestructive subtypes. The median SUV_peak at the biopsy site was significantly higher in monomorphic PTLD (17.8, interquartile range (IQR):16) than in polymorphic subtypes (9.8, IQR:13.4) and nondestructive (4.1, IQR:6.1) (p = 0.04 and p ≤ 0.01, respectively). An SUV_peak ≥ 24.8 was always indicative of a monomorphic PTLD in our dataset. Nevertheless, there was a considerable overlap in SUV across the different morphologies. Conclusion: The median SUV_peak at the biopsy site was significantly higher in monomorphic PTLD than polymorphic and nondestructive subtypes. However, due to significant SUV overlap across the different subtypes, these values may only serve as an indication of PTLD morphology, and SUV-based parameters cannot replace histopathological classification. Full article

SARS-CoV-2 is the novel member of coronavirus responsible for the worldwide pandemic COVID-19, affecting all types of people. In this context, established research identified pregnant women as a susceptible group of SARS-CoV-2 infection, although there is still limited data regarding the real impact of COVID-19 in this group. With that purpose, we conducted a systematic review describing the maternal-fetal results of pregnant women infected by SARS-CoV-2, in aim to analyze the profile of the obstetric patients according to the country of origin of the publication. A total of 38 articles were included in this systematic review with 2670 patients from 7 countries, with 20 works published from China (52.6%). We reported significative differences according to the median maternal age, with Spain as the country with the highest age (34.6 years); The percentage of tabaquism; proportion of symptomatic patients in the triage; type of radiological exam (China and France conduct CT scans on all their patients in comparison to the use of chest X-Ray in the rest of the countries studied); percentages of C-sections (83.9% in China; 35.9% Spain, p < 0.001); maternal mortality rate, proportion of patients who need treatments, the use of antivirals, antibiotics, and anticoagulants as well as measurements of the newborns. Perinatal results are favorable in the majority of countries, with very low rates of vertical transmission in the majority of works. The studies collected in this review showed moderate to high index of quality. The different works describe the affectation during the first wave of the pandemic, where the pregnant woman with SARS-CoV-2 infection is generally symptomatic during the third trimester of gestation along with other factors associated with worse prognosis of the disease, such as higher age, body mass index, and further comorbidities developed during pregnancy. In the obstetric patient, proportion of C-sections are elevated together with prematurity, increasing maternal perinatal morbimortality. Differences found between countries could be based on the proper profile of the patient in each region, the period of the pandemic directly affecting how it was managed, and the variations regarding in situ medical attention. Full article

Multiple diagnostic tools are used to evaluate psoriasis and atopic dermatitis (AD) severity, but most of them are based on subjective components. Transepidermal water loss (TEWL) and temperature are skin barrier function parameters that can be objectively measured and could help clinicians to evaluate disease severity accurately. Thus, the aims of this study are: (1) to compare skin barrier function between healthy skin, psoriatic skin and AD skin; and (2) to assess if skin barrier function parameters could predict disease severity. A cross-sectional study was designed, and epidermal barrier function parameters were measured. The study included 314 participants: 157 healthy individuals, 92 psoriatic patients, and 65 atopic dermatitis patients. TEWL was significantly higher, while stratum corneum hydration (SCH) (8.71 vs. 38.43 vs. 44.39 Arbitrary Units (AU)) was lower at psoriatic plaques than at uninvolved psoriatic skin and healthy controls. Patients with both TEWL > 13.85 g·m⁻²h⁻¹ and temperature > 30.85 °C presented a moderate/severe psoriasis (psoriasis area severity index (PASI) ≥ 7), with a specificity of 76.3%. TEWL (28.68 vs. 13.15 vs. 11.60 g·m⁻² h⁻¹) and temperature were significantly higher, while SCH (25.20 vs. 40.95 vs. 50.73 AU) was lower at AD eczematous lesions than uninvolved AD skin and healthy controls. Patients with a temperature > 31.75 °C presented a moderate/severe AD (SCORing Atopic Dermatitis (SCORAD) ≥ 37) with a sensitivity of 81.8%. In conclusion, temperature and TEWL values may help clinicians to determine disease severity and select patients who need intensive treatment. Full article

This study aimed to determine the relation of best corrected visual acuity (BCVA) and low luminance visual acuity (LLVA) in proliferative diabetic retinopathy (PDR) following treatment with either aflibercept or pan-retinal photocoagulation (PRP). The study was conducted as a post-hoc analysis of the CLARITY trial in which naïve and PRP treated PDR patients were randomised to receive either aflibercept or PRP. BCVA and LLVA were assessed at baseline and at week 52. Our analyses showed that the BCVA and LLVA correlate well in treatment naïve PDR with an average low luminance deficit of 11.79 Early Treatment Diabetic Retinopathy Score (ETDRS) letters. However, LLVA at lower levels of BCVA showed more variance. Post aflibercept therapy, the mean change in BCVA and LLVA at 52 weeks after aflibercept was +2.1 (SD 6.05) letters and +0.39 (SD 5.6) letters, respectively. Similarly, after PRP, it was −2.5 (SD 4.9) letters and −1.9 (SD 8.7) letters, respectively. When comparing treatment arms, BCVA change was found to be statistically significant (p < 0.001) whereas LLVA was not (p = 0.11). These findings show that LLVA does not respond as well as BCVA following any treatment for PDR, even though BCVA and LLVA both test foveal function. Full article

Background: The acute physiological changes induced by focal retinal photocoagulation (PC) have been largely unexplored. Methods: This was a case-series study. We recorded multifocal electroretinograms (mfERGs) just before PC, and mfERGs were also recorded 5′, 15′, one hour, 24 h, and one week after the PCs. Transient changes of mfERGs were analyzed in eyes which underwent PCs to treat diabetic macular edema. The mfERGs recorded from the predominantly irradiated area and that from non-irradiated areas were analyzed separately. Results: Fifteen eyes of 15 patients were included in this study. The mfERGs elicited from non-irradiated areas did not change after PC, but the mfERGs elicited from the irradiated area changed with time; the amplitude was larger at 60′ than that before (p < 0.05) and at 5′ after PC (p < 0.01) and significantly smaller at 24 h and 1 week than that before and at 60′ after the PC (p < 0.01). The implicit time was significantly prolonged after PC. mfERG on irradiated area with the severe diabetic change was less altered after PCs. Conclusions: The transient increase in the amplitude at 60′ likely resulted from a biological amplification of partially damaged cells adjacent to the PC spots. The mfERGs manifested the dynamic alterations of the retinal function following PCs. Full article

(1) Background: Epi- and Paracardial Adipose Tissue (EAT, PAT) have been spotlighted as important biomarkers in cardiological assessment in recent years. Since biomarker quantification is an increasingly important method for clinical use, we wanted to examine fully automated EAT and PAT quantification for possible use in cardiovascular risk stratification. (2) Methods: 966 patients with intermediate Framingham risk scores for Coronary Artery Disease referred for coronary calcium scans were included in clinical routine retrospectively. The Coronary Artery Calcium Score (CACS) was extracted and tissue quantification was performed by a deep learning network. (3) Results: The Computed Tomography (CT) segmentations predicted by the network indicated no significant correlation between EAT volume and EAT radiodensity when compared to Agatston score (r = 0.18, r = −0.09). CACS 0 category patients showed significantly lower levels of total EAT and PAT volumes and higher EAT and PAT densities than CACS 1–99 category patients (p < 0.01). Notably, this difference did not reach significance regarding EAT attenuation in male patients. Women older than 50 years, thus more likely to be postmenopausal, were shown to be at higher risk of coronary calcification (p < 0.01, OR = 4.59). CACS 1–99 vs. CACS ≥100 category patients remained below significance level (EAT volume: p = 0.087, EAT attenuation: p = 0.98). (4) Conclusions: Our study proves the feasibility of a fully automated adipose tissue analysis in clinical cardiac CT and confirms in a large clinical cohort that volume and attenuation of EAT and PAT are not correlated with CACS. Broadly available deep learning based rapid and reliable tissue quantification should thus be discussed as a method to assess this biomarker as a supplementary risk predictor in cardiac CT. Full article

Background: Laser interstitial thermal therapy (LITT) is a minimal invasive neurosurgical technique for the treatment of brain tumors. Results of LITT have been reported in a case series of patients with deep seated and/or recurrent glioblastoma or cerebral metastases. With this review we aim to summarize the currently available evidence regarding safety and effectiveness of LITT in patients with newly diagnosed glioblastoma (nGBM). Methods: A literature search was performed using electronic databases (PubMed and Embase). Papers were assessed for the methodological quality using the Risk Of Bias In Non- randomised Studies - of Interventions (ROBINS-I) tool, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to assess the quality of the evidence. Results: We identified 835 papers of which only 11 articles were eligible for our review. All papers suffered from serious or critical risk of bias, and the quality of evidence was graded as very low according to the GRADE criteria. None of the studies was randomized and reporting of confounders and other parameters was poor. Median overall survival (OS) ranged from 4.1 to 32 months and progression free survival (PFS) from 2 to 31 months. The mean complication rate was 33.7%. No quality of life or cost-effectiveness data were reported. Conclusions: Due to the low quality of the studies, it is not possible to draw firm conclusions regarding the (cost) effectiveness of LITT in patients with newly diagnosed glioblastoma. The low quality of evidence shows the need for a well-designed prospective multicenter randomized controlled trial. Full article

Vascular dysfunction is known to be an initiator of the development and progression of cardiovascular diseases (CVDs). However, there is paucity of information on the relationship of vascular dysfunction with cardiovascular risk factors in children of African ancestry. This study investigated the relationship between cardiovascular risk factors and vascular function in South African children of African ancestry. A cross-sectional study on 6–9-year-old children in randomly selected rural and urban schools of the Eastern Cape Province of South Africa was conducted. General anthropometric indices were measured, followed by blood pressure (BP) measurements. The pulse wave velocity (PWV) was measured using a Vicorder. Albumin to creatinine ratio (ACR), asymmetric dimethylarginine (ADMA), 8-hydroxy-2deoxyguanosine (8-OHdG) and thiobarbituric acid reactive substance (TBARS) were assayed in urine. Children from urban settings (10.8%) had a higher prevalence of overweight/obesity than their rural counterparts (8.5%) while the prevalence of elevated/high blood pressure was higher in rural (23.2%) than urban children (19.0%). Mean arterial blood pressure (MAP) and diastolic blood pressure (DBP) increased with increasing PWV (p < 0.05). Body mass index (BMI), diastolic blood pressure (DBP) and mean arterial blood pressure (MAP) positively associated (p < 0.05) with PWV. Creatinine, albumin and ACR significantly (p < 0.005) increased with increasing ADMA. ADMA associated positively (p < 0.05) with creatinine and 8-OHdG. In conclusion, vascular dysfunction was associated with obesity, high blood pressure, oxidative stress and microalbuminuria in South African children of African ancestry. Full article

Hepatocellular carcinoma (HCC) incidence has dramatically decreased in patients infected with HCV and HBV due to the widespread use of highly effective antiviral agents. Nevertheless, a substantial proportion of patients with advanced fibrosis or cirrhosis following HCV clearance of in case of HBV control whatever the stage of fibrosis remains at risk of liver cancer development. Cancer predictors in these virus-free patients include routine parameters estimating coexisting comorbidities, persisting liver inflammation or function impairment, and results of non-invasive tests which can be easily combined into HCC risk scoring systems. The latter enables stratification according to various liver cancer incidences and allocation of patients into low, intermediate or high HCC risk probability groups. All international guidelines endorse lifelong surveillance of these patients using semi-annual ultrasound, with known sensibility issues. Refining HCC prediction in this growing population ultimately will trigger personalized management using more effective surveillance tools such as contrast-enhanced imaging techniques or circulating biomarkers while taking into account cost-effectiveness parameters. Full article

Anxiety has been estimated to occur in 21–96% and depression in 27–79% of patients with chronic obstructive pulmonary disorder (COPD). We found a scarcity of literature providing evidence on how virtual reality (VR) therapy affects the intensity of depressive and anxiety symptoms and stress levels in COPD patients undergoing in-hospital pulmonary rehabilitation (PR). This study enrolled 50 COPD patients with symptoms of stress, depression, and anxiety, randomly assigned to one of two groups. The two groups participated in the traditional PR programme additionally: the VR-group performed 10 sessions of immersive VR-therapy and the control group performed 10 sessions of Schultz autogenic training. Comparison of the changes in stress levels and depressive and anxiety symptoms was the primary outcome. Analysis of the results showed a reduction in stress levels only in the VR-group (p < 0.0069), with a medium effect size (d = 0.353). The symptoms of depression (p < 0.001, d = 0.836) and anxiety (p < 0.0009, d = 0.631) were statistically significantly reduced only in the VR-group, with a strong effect size. The enrichment of pulmonary rehabilitation with immersive VR therapy brings benefits in terms of mood improvement and reduction in anxiety and stress in patients with COPD. Full article

The endometrium is necessary for implantation, complete development of the placenta, and a successful pregnancy. The endometrium undergoes repeated cycles of proliferation, decidualization (differentiation), and shedding during each menstrual cycle. The endometrium—including stromal, epithelial, vascular endothelial, and immune cells—is both functionally and morphologically altered in response to progesterone, causing changes in the number and types of immune cells. Immune cells make up half of the total number of endometrial cells during implantation and menstruation. Surprisingly, immune tolerant cells in the endometrium (uterine natural killer cells, T cells, and macrophages) have two conflicting functions: to protect the body by eliminating pathogenic microorganisms and other pathogens and to foster immunological change to tolerate the embryo during pregnancy. One of the key molecules involved in this control is the cytokine interleukin-15 (IL-15), which is secreted by endometrial stromal cells. Recently, it has been reported that IL-15 is directly regulated by the transcription factor heart- and neural crest derivatives-expressed protein 2 in endometrial stromal cells. In this review, we outline the significance of the endometrium and immune cell population during menstruation and early pregnancy and describe the factors involved in immune tolerance and their involvement in the establishment and maintenance of pregnancy. Full article

Intervention studies have shown that n-3 polyunsaturated fatty acid (PUFA) supplementation is effective for the treatment of meibomian gland dysfunction (MGD). Ointment containing an analog of vitamin D has also been found to improve symptoms and signs of MGD. We have now evaluated the relation of MGD prevalence to dietary intake of fatty acids (FAs) and vitamin D among a Japanese population. Subjects comprised 300 adults aged 20 to 92 years residing on Takushima Island. MGD was diagnosed on the basis of subjective symptoms, lid margin abnormalities, and meibomian gland obstruction. Dietary FA and vitamin D intake was estimated with a brief-type self-administered diet history questionnaire. MGD prevalence was 35.3%. Multivariate adjusted odds ratios (95% confidence intervals) between extreme quintiles of intake for MGD prevalence were 0.40 (0.16–0.97) for total fat, 0.40 (0.17–0.97) for saturated FAs, 0.40 (0.17–0.97) for oleic acid, 0.52 (0.23–1.18) for n-3 PUFAs, 0.63 (0.27–1.49) for n-6 PUFAs, 1.32 (0.59–2.95) for the n-6/n-3 PUFA ratio, and 0.38 (0.17–0.87) for vitamin D. Total fat, saturated FA, oleic acid, and vitamin D intake may thus be negatively associated with MGD prevalence in the Japanese. Full article

Background: The surgical approach and choice of drainage veins for uterus transplantation living-donor surgery have been investigated to reduce invasiveness. Methods: A thorough search of the PubMed database was conducted. The search was not limited by language or date of publication. The data were collected on 13 October 2020. Two reviewers independently assessed each article and determined eligibility for inclusion in the review article. Inclusion criteria were English peer-reviewed articles reporting surgical information or postoperative course, articles regarding animal research on UTx, UTx on deceased donors, or not original articles. Results: Of the 51 operations within 26 articles reviewed, the mean operative time was shortest in the laparoscopic approach, and longest in the robot-assisted approach. The mean blood loss was less in the laparoscopic and robot-assisted approaches than in the open approach. In cases where the uterine veins were not preserved, the mean operative time was shortened by each approach and the mean blood loss decreased with the laparoscopic and robot-assisted approaches. Conclusions: These procedures may contribute to less invasive living-donor surgery. Full article

The aim of diabetes care of pregnant women with gestational diabetes mellitus (GDM) is to attain pregnancy outcomes including rates of large-for-gestational-age (LGA) newborns, pre-eclampsia, C-sections (CS) and other neonatal outcomes similar to those of the non-GDM pregnant population. Obesity and excessive weight gain during pregnancy have been shown to also impact perinatal outcome. Since GDM is frequently associated with elevated body mass index (BMI), we evaluated the impact of maternal prepregnancy BMI, development of GDM and gestational weight gain (GWG) during pregnancy on perinatal outcome. We compared 614 GDM patients with 5175 non-diabetic term deliveries who gave birth between 2012 and 2016. Multivariate regression analysis was used to evaluate the independent contribution of each factor on selected perinatal outcome variables. Additionally, subgroup analysis for obese (BMI ≥ 30 kg/m²) and non-obese women (BMI < 30 kg/m²) was performed. LGA was significantly influenced by BMI, GWG and GDM, while Neonatal Intensive Care Unit (NICU) admission was solely impacted by GDM. Maternal outcomes were not dependent on GDM but on GWG and prepregnancy BMI. These results remained significant in the non-obese subgroup only. Thus, GDM still affects perinatal outcomes and requires further improvement in diabetic care and patient counseling. Full article

Background: Familial multiple coagulation factor deficiencies (FMCFDs) are a group of inherited hemostatic disorders with the simultaneous reduction of plasma activity of at least two coagulation factors. As consequence, the type and severity of symptoms and the management of bleeding/thrombotic episodes vary among patients. The aim of this study was to identify the underlying genetic defect in patients with FMCFDs. Methods: Activity levels were collected from the largest cohort of laboratory-diagnosed FMCFD patients described so far. Genetic analysis was performed using next-generation sequencing. Results: In total, 52 FMCFDs resulted from coincidental co-inheritance of single-factor deficiencies. All coagulation factors (except factor XII (FXII)) were involved in different combinations. Factor VII (FVII) deficiency showed the highest prevalence. The second group summarized 21 patients with FMCFDs due to a single-gene defect resulting in combined FV/FVIII deficiency or vitamin K–dependent coagulation factor deficiency. In the third group, nine patients with a combined deficiency of FVII and FX caused by the partial deletion of chromosome 13 were identified. The majority of patients exhibited bleeding symptoms while thrombotic events were uncommon. Conclusions: FMCFDs are heritable abnormalities of hemostasis with a very low population frequency rendering them orphan diseases. A combination of comprehensive screening of residual activities and molecular genetic analysis could avoid under- and misdiagnosis. Full article

Among risk factors (apart from smoking) likely involved in bladder cancer (BCa), metabolic syndrome (MS), obesity and type 2 diabetes mellitus (T2DM) have been explored with contrasting results. In spite of these studies, there is little data on the association between nonalcoholic fatty liver disease (NAFLD), its main driver, i.e., insulin resistance (IR), and BCa. Implanting a cross-sectional retrospective study we tried to investigate both NAFLD and IR prevalence in a hospital based population of BCa patients. We studied laboratory data from 204 patients with histologically confirmed non metastatic BCa and 50 subjects with no BCa, but with bladder diseases (no Ca BD). We evaluated the presence of NAFLD by the triglycerides/glucose Index (TyG Index), using a cut-off of 0.59 and by the Aspartate Aminotransferase/Alanine Aminotransferase AST/ALT ratio. IR was assessed by the same TyG Index (cut-off 4.68) and the triglycerides/High-Density Lipoprotein HDL ratio (cut-off 2.197). The diagnosis of impaired fasting glucose (IFG), condition of prediabetes, as well as that of T2DM was assessed according to canonical guidelines. The TyG Index predicted NAFLD presence in both groups (p = 0.000), but the BCa group showed a major percentage of NAFLD cases with respect to no Ca BD group (59% versus 40%). A greater proportion of IR (47%) in BCa group than in no Ca BD one (37%) was evidenced by the TyG Index with its median value significantly different (p = 0.0092). This high rate of IR in the BCa group was confirmed by the triglycerides/HDL ratio (p = 0.02). Prediabetes and T2DM were more prevalent in the BCa group than no Ca BD group (p = 0.024). In this study a consistent NAFLD presence was found in BCa patients. This is an important comorbidity factor that deserves further consideration in prospective studies. The higher prevalence of NAFLD, IR, prediabetes and T2DM in the BCa group evidences the need that these disorders should be reckoned as adjunct factors that could impact on this cancerous disease. Full article

Gender dysphoria (GD) is characterized by distress due to an incongruence between experienced gender and sex assigned at birth. Sex-differentiated brain regions are hypothesized to reflect the experienced gender in GD and may play a role in sexual orientation development. Magnetic resonance brain images were acquired from 16 GD adolescents assigned female at birth (AFAB) not receiving hormone therapy, 17 cisgender girls, and 14 cisgender boys (ages 12–17 years) to examine three morphological and microstructural gray matter features in 76 brain regions: surface area (SA), cortical thickness (CT), and T1 relaxation time. Sexual orientation was represented by degree of androphilia-gynephilia and sexual attraction strength. Multivariate analyses found that cisgender boys had larger SA than cisgender girls and GD AFAB. Shorter T1, reflecting denser, macromolecule-rich tissue, correlated with older age and stronger gynephilia in cisgender boys and GD AFAB, and with stronger attractions in cisgender boys. Thus, cortical morphometry (mainly SA) was related to sex assigned at birth, but not experienced gender. Effects of experienced gender were found as similarities in correlation patterns in GD AFAB and cisgender boys in age and sexual orientation (mainly T1), indicating the need to consider developmental trajectories and sexual orientation in brain studies of GD. Full article

Given the estrogen-dependence associated with endometriosis, hyper-stimulation associated with assisted reproduction treatment may exacerbate the disease process and adversely affect endometrial receptivity and subsequent implantation. In this way, a freeze-all deferred embryo transfer (ET) approach may benefit patients with endometriosis, although controversy exists regarding the mechanism of endometriosis-associated infertility and benefits of deferred ET on endometrial receptivity. Hence, the purpose of this study was to compare in vitro fertilization (IVF) outcomes in women with endometriosis, diagnosed by histology, undergoing fresh versus deferred-ET after elective cryopreservation. Of the 728 women included, no significant differences were observed in baseline patient characteristics and response to gonadotrophin stimulation between fresh and deferred ET groups. Furthermore, no significant differences in implantation rate (49.7 vs. 49.9%, p = 0.73), clinical pregnancy rate (40.9 vs. 39.9%, p = 0.49), and miscarriage rate (9.4 vs. 9.9%, p = 0.63) were observed between fresh and deferred ET groups, respectively. Hence, contrary to previous studies, our results suggest that a deferred ET “freeze-all” IVF strategy does not improve early pregnancy outcomes among women with endometriosis. However, prospective studies are required to validate these findings and further insight into the etiology and pathogenesis of endometriosis-associated infertility are necessary to optimize IVF protocols in this population. Full article

Background: Prevalence estimates for sarcopenia vary depending on the ascertainment criteria and thresholds applied. We aimed to estimate the prevalence of sarcopenia using two international definitions but employing Australian population-specific cut-points. Methods: Participants (n = 665; 323 women) aged 60–96 years old were from the Geelong Osteoporosis Study. Handgrip strength (HGS) was measured by dynamometers and appendicular lean mass (ALM) by whole-body dual-energy X-ray absorptiometry. Physical performance was assessed using gait speed (GS, men only) and/or the timed up-and-go (TUG) test. Using cut-points equivalent to two standard deviations (SDs) below the mean young reference range from the same population and recommendations from the European Working Group on Sarcopenia in Older People (EWGSOP), sarcopenia was identified by low ALM/height² (<5.30 kg for women; <6.94 kg for men) + low HGS (<16 kg women; <31 kg men); low ALM/height² + slow TUG (>9.3 s); low ALM/height² + slow GS (<0.8 m/s). For the Foundation for the National Institutes of Health (FNIH) equivalent, sarcopenia was identified as low ALM/BMI (<0.512 m² women, <0.827 m² men) + low HGS (<16 kg women, <31 kg men). Receiver Operating Characteristic curves were also applied to determine optimal cut-points for ALM/BMI (<0.579 m² women, <0.913 m² men) that discriminated poor physical performance. Prevalence estimates were standardized to the Australian population and compared to estimates using international thresholds. Results: Using population-specific cut-points and low ALM/height² + HGS, point-estimates for sarcopenia prevalence were 0.9% for women and 2.9% for men. Using ALM/height² + TUG, prevalence was 2.5% for women and 4.1% for men, and using ALM/height² + GS, sarcopenia was identified for 1.6% of men. Using ALM/BMI + HGS, prevalence estimates were 5.5–10.4% for women and 11.6–18.4% for men. Conclusions: This study highlights the range of prevalence estimates that result from employing different criteria for sarcopenia. While population-specific criteria could be pertinent for some populations, a consensus is needed to identify which deficits in skeletal muscle health are important for establishing an operational definition for sarcopenia. Full article