Abdominal obesity predominates in menopausal women (MW) and contributes to the development of metabolic syndrome (MetS). It is associated with increased mortality related to cardiovascular disease, diabetes and fatty liver disease. The effects of whole-body cryotherapy (WBC) on body composition and the blood concentration of irisin, interleukin-6 (IL-6) and C-reactive proteins (CRP) in MW with MetS and in healthy women (HW), were assessed. The study included 19 women with MetS (61.53 ± 3.99 y, BMI 30.09 ± 4.98 kg/m²) and 18 HW (60.28 ± 3.63 y, BMI 25.50 ± 2.37 kg/m²) who were subjected to 20 WBC treatments at −130 °C for 3 min daily. In both groups, body mass (BM), BMI, abdominal circumference, triceps skinfold, total fat mass and percentage of leg fat significantly decreased after 20 WBC sessions. Additionally, the percentage of total, trunk and android fat in the MetS group were significantly decreased after 20 WBC applications. Waist circumference (WC) and waist-to-height ratio (WHtR) significantly decreased in both groups, and in the HW group, hip circumference and abdominal skinfold also significantly decreased after 10 WBC and 20 WBC treatments. In both groups, the concentration of plasma irisin significantly increased after 1 WBC and 10 WBC exposures, while the concentration of IL-6 significantly increased only in MetS group after 10 WBC and 20 WBC, and were significantly higher than in HW. CRP concentrations were significantly higher in the MetS group than in HW before 1 WBC, after 1 WBC and 10 WBC sessions, but not after 20. In the MetS group, there were significant negative correlations between the change in irisin level and the changes in WC and BM, and between the level of irisin and the change in percentage of total fat, and significant negative correlations between the change in IL-6 level and changes in WC, waist-to-hip ratio and WHtR. Whole-body cryotherapy, assuming the application of 20 treatments in the series, reduces abdominal obesity in menopausal women indirectly through the secretion of irisin and IL-6, and can be used as adjunctive therapy in the treatment of metabolic syndrome. Our conclusion is limited to menopausal women with low–moderate physical activity for whom its level as well as diet were not changed during the treatment. Full article

Earlier or preprocedural identification of occlusion pathomechanism is crucial for effective endovascular treatment. As leptomeningeal collaterals tend to develop well in chronic ischemic conditions such as intracranial atherosclerosis (ICAS), we investigated whether leptomeningeal collaterals can be a preprocedural marker of ICAS-related large vessel occlusion (ICAS-LVO) in endovascular treatment. A total of 226 patients who underwent endovascular treatment were retrospectively reviewed. We compared the pattern of leptomeningeal collaterals between patients with ICAS-LVO and without. Leptomeningeal collaterals were assessed by preprocedural computed tomography angiography (CTA) and basically categorized by three different collateral assessment methods. Better leptomeningeal collaterals were significantly associated with ICAS-LVO, although they were not independent for ICAS-LVO. When leptomeningeal collaterals were dichotomized to incomplete (<100%) and complete (100%), the latter was significantly more frequent in patients with ICAS-LVO (52.5% versus 20.4%) and remained an independent factor for ICAS-LVO (odds ratio, 3.32; 95% confidence interval, 1.52–7.26; p = 0.003). The area under the curve (AUC) value of complete leptomeningeal collateral supply was 0.660 for discrimination of ICAS-LVO. Incomplete leptomeningeal collateral supply was not likely ICAS-LVO, based on the high negative predictive value (88.6%). Considering its negative predictive value and the independent association between complete leptomeningeal collateral supply and ICAS-LVO, leptomeningeal collaterals could be helpful in the preprocedural determination of occlusion pathomechanism. Full article

Cardiac mechanical energetic efficiency is the ratio of external work (EW) to the total energy consumption. EW performed by the left ventricle (LV) during a single beat is represented by LV stroke work and may be calculated from the pressure–volume loop area (PVLA), while energy consumption corresponds to myocardial oxygen consumption (MVO₂) expressed on a per-beat basis. Classical early human studies estimated total mechanical LV efficiency at 20–30%, whereas the remaining energy is dissipated as heat. Total mechanical efficiency is a joint effect of the efficiency of energy transfer at three sequential stages. The first step, from MVO₂ to adenosine triphosphate (ATP), reflects the yield of oxidative phosphorylation (i.e., phosphate-to-oxygen ratio). The second step, from ATP split to pressure–volume area, represents the proportion of the energy liberated during ATP hydrolysis which is converted to total mechanical energy. Total mechanical energy generated per beat—represented by pressure–volume area—consists of EW (corresponding to PVLA) and potential energy, which is needed to develop tension during isovolumic contraction. The efficiency of the third step of energy transfer, i.e., from pressure–volume area to EW, decreases with depressed LV contractility, increased afterload, more concentric LV geometry with diastolic dysfunction and lower LV preload reserve. As practical assessment of LV efficiency poses methodological problems, De Simone et al. proposed a simple surrogate measure of myocardial efficiency, i.e., mechano-energetic efficiency index (MEEi) calculated from LV stroke volume, heart rate and LV mass. In two independent cohorts, including a large group of hypertensive subjects and a population-based cohort (both free of prevalent cardiovascular disease and with preserved ejection fraction), low MEEi independently predicted composite adverse cardiovascular events and incident heart failure. It was hypothesized that the prognostic ability of low MEEi can result from its association with both metabolic and hemodynamic alterations, i.e., metabolic syndrome components, the degree of insulin resistance, concentric LV geometry, LV diastolic and discrete systolic dysfunction. On the one part, an increased reliance of cardiomyocytes on the oxidation of free fatty acids, typical for insulin-resistant states, is associated with both a lower yield of ATP per oxygen molecule and lesser availability of ATP for contraction, which might decrease energetic efficiency of the first and second step of energy transfer from MVO₂ to EW. On the other part, concentric LV remodeling and LV dysfunction despite preserved ejection fraction can impair the efficiency of the third energy transfer step. In conclusion, the association of low MEEi with adverse cardiovascular outcome might be related to a multi-step impairment of energy transfer from MVO₂ to EW in various clinical settings, including metabolic syndrome, diabetes, hypertension and heart failure. Irrespective of theoretical considerations, MEEi appears an attractive simple tool which couldt improve risk stratification in hypertensive and diabetic patients for primary prevention purposes. Further clinical studies are warranted to estimate the predictive ability of MEEi and its post-treatment changes, especially in patients on novel antidiabetic drugs and subjects with common metabolic diseases and concomitant chronic coronary syndromes, in whom the potential relevance of MEE can be potentiated by myocardial ischemia. Full article

Sarcoidosis is a granulomatous disorder of unknown etiology characterized by noncaseating granulomas virtually in every organ and tissue. This finding represents the most important diagnostic clue to reach a correct definition of sarcoidosis, although the biopsy is invasive and has several risk procedures. Several efforts are made to suspect the diagnosis of sarcoidosis by combining noninvasive elements, in particular from imaging, though these findings are often nonspecific and reflect the wide multifactorial pathogenesis. Every effort should be made to obtain a detailed radiological picture that, if associated with a suggestive clinical picture, could avoid the need of biopsy in some specific cases. In this narrative review, we aim to describe main computed tomography (CT) features of pulmonary and abdominal sarcoidosis, by reporting strengths and limits of this technique, in particular for the identification of extrapulmonary, isolated disease. Full article

Background: Stromal vascular fraction (SVF) has recently emerged as a potential therapeutic modality, due to its multipotent cellular components in tissue regeneration. Systemic sclerosis (SSc) is a progressive autoimmune disease that results in hand disability by skin fibrosis and microangiopathies. We performed an open-label study to investigate the efficacy and safety of SVF injection in SSc patients (Clinical Trial number: NCT03060551). Methods: We gathered 20 SSc patients with hand disability, planning for a 24-week follow-up period. SVF was extracted from autologous adipose tissues, processed by the closed system kit, and injected into each finger of SSc patients. We observed various efficacy and safety profiles at each follow-up visit. Results: Among the 20 initially enrolled patients, eighteen received SVF injection, and were completely followed-up for the whole study period. Patients received 3.61 × 10⁶ mesenchymal stem cells into each finger on average. Skin fibrosis, hand edema, and quality of life were significantly improved, and 31.6% of active ulcers were healed at 24 weeks after injections. Semiquantitative results of nailfold capillary microscopy were ameliorated. There was no single serious adverse event related to the procedure. Conclusions: Injection of SVF derived from autologous adipose tissues is tolerable, and shows clinical efficacy in SSc patients. Full article

Background: Reducing the number of ischemic strokes in patients with atrial fibrillation despite oral anticoagulation remains an important, yet largely unsolved challenge. Therefore, we assessed the etiology of ischemic strokes despite anticoagulation with vitamin K antagonists (VKA) or non-VKA oral anticoagulants (NOACs). Methods: Patients with known atrial fibrillation (AF), treatment with VKA or NOAC, and acute ischemic stroke admitted between 2015 and 2018 (1st half) were identified from the hospital database. Brain imaging data were independently reviewed. An integrated etiologic classification according to the ASCOD system was made. Medication errors (admission INR <2.0 in the VKA- or NOAC-specific concentration <10 ng/mL) or dosage/dosing errors were also analyzed. Results: Of 3610 patients screened, n = 341 were included (VKA, n = 127; NOAC, n = 214). An overall increasing rate of OAC-associated stroke per year was observed. In 95.3% of patients with adequate diagnostic work-up (n = 321/337), at least one additional potential, uncertain, or unlikely non-cardiac cause of stroke was identified. More patients in the VKA than in the NOAC group had a medication error (81/127, 63.8% vs. 102/205, 49.8%; p = 0.013). Conclusions: Stroke risk factors despite atrial fibrillation were highly prevalent. Although less common with NOACs than VKAs, medication errors are still frequent. Full article

Facioscapulohumeral muscular dystrophy (FSHD) is a common muscle dystrophy typically affecting patients within their second decade. Patients initially exhibit asymmetric facial and humeral muscle damage, followed by lower body muscle involvement. FSHD is associated with a derepression of DUX4 gene encoded by the D4Z4 macrosatellite located on the subtelomeric part of chromosome 4. DUX4 is a highly regulated transcription factor and its expression in skeletal muscle contributes to multiple cellular toxicities and pathologies ultimately leading to muscle weakness and atrophy. Since the discovery of the FSHD candidate gene DUX4, many cell and animal models have been designed for therapeutic approaches and clinical trials. Today there is no treatment available for FSHD patients and therapeutic strategies targeting DUX4 toxicity in skeletal muscle are being actively investigated. In this review, we will discuss different research areas that are currently being considered to alter DUX4 expression and toxicity in muscle tissue and the cell and animal models designed to date. Full article

Background: The aim of this study was to investigate the diagnostic accuracy of symptoms and signs in healthcare workers (HCW) with Sars-CoV-2. Methods: This was a case-control study. Cases consisted of symptomatic healthcare workers who had a positive SARS-CoV-2 real-time polymerase chain reaction (RT-PCR) test, while controls were symptomatic healthcare workers with a negative RT-PCR test. For each symptom, ROCs were plotted. Diagnostic accuracy was calculated using the sensitivity, specificity, and positive and negative predictive values. A logistic regression analysis was carried out for calculating the OR (95% CI) for each symptom associated to the SARS-CoV-2 positivity. Results: We recruited 30 cases and 75 controls. Fever had the best sensitivity while dyspnea, anosmia, and ageusia had the highest specificity. The highest PPVs were found again for dyspnea (75%), anosmia (73.7%), and ageusia (66.7%). Lastly, the highest NPVs were related to anosmia (81.4%) and ageusia (79.3%). Anosmia (OR = 14.75; 95% CI: 4.27–50.87), ageusia (OR = 9.18; 95% CI: 2.80–30.15), and headache (OR = 3.92; 95% CI: 1.45–10.56) are significantly associated to SARS-CoV-2 positivity. Conclusions: Anosmia and ageusia should be considered in addition to the well-established fever, cough, and dyspnea. In a resource-limited setting, this method could save time and money. Full article

Low-to-moderate quality meta-analytic evidence shows that motor control stabilisation exercise (MCE) is an effective treatment of non-specific low back pain. A possible approach to overcome the weaknesses of traditional meta-analyses would be that of a prospective meta-analyses. The aim of the present analysis was to generate high-quality evidence to support the view that motor control stabilisation exercises (MCE) lead to a reduction in pain intensity and disability in non-specific low back pain patients when compared to a control group. In this prospective meta-analysis and sensitivity multilevel meta-regression within the MiSpEx-Network, 18 randomized controlled study arms were included. Participants with non-specific low back pain were allocated to an intervention (individualized MCE, 12 weeks) or a control group (no additive exercise intervention). From each study site/arm, outcomes at baseline, 3 weeks, 12 weeks, and 6 months were pooled. The outcomes were current pain (NRS or VAS, 11 points scale), characteristic pain intensity, and subjective disability. A random effects meta-analysis model for continuous outcomes to display standardized mean differences between intervention and control was performed, followed by sensitivity multilevel meta-regressions. Overall, 2391 patients were randomized; 1976 (3 weeks, short-term), 1740 (12 weeks, intermediate), and 1560 (6 months, sustainability) participants were included in the meta-analyses. In the short-term, intermediate and sustainability, moderate-to-high quality evidence indicated that MCE has a larger effect on current pain (SMD = −0.15, −0.15, −0.19), pain intensity (SMD = −0.19, −0.26, −0.26) and disability (SMD = −0.15, −0.27, −0.25) compared with no exercise intervention. Low-quality evidence suggested that those patients with comparably intermediate current pain and older patients may profit the most from MCE. Motor control stabilisation exercise is an effective treatment for non-specific low back pain. Sub-clinical intermediate pain and middle-aged patients may profit the most from this intervention. Full article

Survivorship care that is shared between oncology and primary care providers may be a suitable model to effectively and efficiently care for the growing survivor population, however recommendations supporting implementation are lacking. This qualitative study aimed to explore health care professionals’ (HCPs) perceived facilitators and barriers to the implementation, delivery and sustainability of shared survivorship care. Data were collected via semi-structured focus groups and analysed by inductive thematic analysis. Results identified four overarching themes: (1) considerations for HCPs; (2) considerations regarding patients; (3) considerations for planning and process; and (4) policy implications. For HCPs, subthemes included general practitioner (GP, primary care physician) knowledge and need for further training, having clear protocols for follow-up, and direct communication channels between providers. Patient considerations included identifying patients suitable for shared care, discussing shared care with patients early in their cancer journey, and patients’ relationships with their GPs. Regarding process, subthemes included rapid referral pathways back to hospital, care coordination, and ongoing data collection to inform refinement of a dynamic model. Finally, policy implications included development of policy to support a consistent shared care model, and reliable and sustainable funding mechanisms. Based on study findings, a set of recommendations for practice and policy were developed. Full article

Sedentary behavior and cognitive impairment have a direct impact on patients’ outcomes. An energy metabolic disorder may be involved in the overlap of these comorbid conditions (motoric cognitive risk (MCR)) in patients with chronic obstructive pulmonary disease (COPD). We aimed to explore the linkage between a proapoptotic protein, growth differentiation factor (GDF)-15, and MCR. Physical activity (PA), cognitive function (Japanese version of the Montreal Cognitive Assessment: MOCA-J), and the serum GDF-15 levels were assessed in healthy subjects (n = 14), asthmatics (n = 22), and COPD patients (n = 28). In the entire cohort, serum GDF-15 had negative correlations with exercise (Ex) (ρ = −0.43, p < 0.001) and MoCA-J (ρ = −0.44, p < 0.001), and Ex and MOCA-J showed a positive correlation (ρ = 0.52, p < 0.0001). Compared to healthy subjects and asthmatics, COPD patients showed the highest serum GDF-15 levels and had a significantly higher proportion of subjects with MCR (both sedentary lifestyle (EX < 1.5) and cognitive risk (MoCA-J ≤ 25)). Also, we found that serum GDF-15 has a screening potential (100% sensitivity) greater than aging (67% sensitivity) for detecting MCR in COPD patients. In conclusion, higher serum GDF-15 had interrelationships with a sedentary lifestyle and cognitive risk. This protein was not disease-specific but could be a screening biomarker to detect MCR related to poor health outcomes of COPD patients. Full article

The underlying molecular mechanisms of the aberrant expression of components of the HLA class I antigen processing and presentation machinery (APM) in tumors leading to evasion from T cell-mediated immune surveillance could be due to posttranscriptional regulation mediated by microRNAs (miRs). So far, some miRs controlling the expression of different APM components have been identified. Using in silico analysis and an miR enrichment protocol in combination with small RNA sequencing, miR-26b-5p and miR-21-3p were postulated to target the 3′ untranslated region (UTR) of the peptide transporter TAP1, which was confirmed by high free binding energy and dual luciferase reporter assays. Overexpression of miR-26b-5p and miR-21-3p in melanoma cells downregulated the TAP1 protein and reduced expression of HLA class I cell surface antigens, which could be reverted by miR inhibitors. Moreover, miR-26b-5p overexpression induced a decreased T cell recognition. Furthermore, an inverse expression of miR-26b-5p and miR-21-3p with TAP1 was found in primary melanoma lesions, which was linked with the frequency of CD8⁺ T cell infiltration. Thus, miR-26-5p and miR-21-3p are involved in the HLA class I-mediated immune escape and might be used as biomarkers or therapeutic targets for HLA class I^low melanoma cells. Full article

Coronavirus disease 2019 (COVID-19) has rapidly become a global pandemic with lung disease representing the main cause of morbidity and mortality. Conventional chest-X ray (CXR) and ultrasound (US) are valuable instruments to assess the extent of lung involvement. We investigated the relationship between CXR scores on admission and the level of medical care required in patients with COVID-19. Further, we assessed the CXR-US correlation to explore the role of ultrasound in monitoring the course of COVID-19 pneumonia. Clinical features and CXR scores were obtained at admission and correlated with the level of intensity of care required [high- (HIMC) versus low-intensity medical care (LIMC)]. In a subgroup of patients, US findings were correlated with clinical and radiographic parameters. On hospital admission, CXR global score was higher in HIMCs compared to LIMC. Smoking history, pO₂ on admission, cardiovascular and oncologic diseases were independent predictors of HIMC. The US score was positively correlated with FiO₂ while the correlation with CXR global score only trended towards significance. Our study identifies clinical and radiographic features that strongly correlate with higher levels of medical care. The role of lung ultrasound in this setting remains undetermined and needs to be explored in larger prospective studies. Full article

Introduction: D-dimer is a diagnostic criterion for periprosthetic joint infection (PJI) of the Musculoskeletal Infection Society (MSIS) in 2018. The aim of this study was to evaluate the serum D-dimer values in comparison to C-reactive protein (CRP) and interleukin-6 (IL-6) for the diagnosis of PJI. Materials and Methods: We included 119 patients (50 women, 69 men; 71 knees, 48 hips) undergoing revision arthroplasty with preoperative assessment of CRP, IL-6, and serum D-dimer. Cases were classified as infected or aseptic based on the MSIS criteria of 2018. Receiver operating curves and Youden’s index were used to define an ideal cut-off value and sensitivity and specificity for the individual parameters, and respective combinations were calculated using cross-tables. Results: The median D-dimer level (2320 vs. 1105 ng/mL; p < 0.001), the median CRP level (4.0 vs. 0.5 mg/dL; p < 0.001), and the median IL-6 level (21.0 vs. 5.0 pg/mL; p < 0.001) were significantly higher in the group of PJI compared to the group with aseptic failure. The calculated optimal cut-off values were 2750 ng/mL (AUC 0.767) for D-dimer, 1.2 mg/dL (AUC 0.914) for CRP, and 10.0 pg/mL (AUC 0.849) for IL-6. D-dimer showed a sensitivity of 38% and specificity of 94%, whereas the CRP and IL-6 had sensitivities of 88% and 76%, and specificities of 87% and 92%, respectively. Conclusion: In comparison with CRP and IL-6, serum D-dimer showed low sensitivity and specificity in our cohort. While CRP and IL-6 combination had the highest sensitivity, a combination of Il-6 and D-dimer or CRP and IL-6 had the highest specificity. Full article

The therapeutic applications of mesenchymal stem cells (MSCs) have been actively explored due to their broad anti-inflammatory and immunomodulatory properties. However, the use of xenogeneic components, including fetal bovine serum (FBS), in the expansion media might pose a risk of xenoimmunization and zoonotic transmission to post-transplanted patients. Here, we extensively compared the physiological functions of human Wharton’s jelly-derived MSCs (WJ-MSCs) in a xeno-free medium (XF-MSCs) and a medium containing 10% FBS (10%-MSCs). Both groups showed similar proliferation potential; however, the 10%-MSCs showed prolonged expression of CD146, with higher colony-forming unit-fibroblast (CFU-F) ability than the XF-MSCs. The XF-MSCs showed enhanced adipogenic differentiation potential and sufficient hematopoietic stem cell (HSC) niche activity, with elevated niche-related markers including CXCL12. Furthermore, we demonstrated that the XF-MSCs had a significantly higher suppressive effect on human peripheral blood-derived T cell proliferation, Th1 and Th17 differentiation, as well as naïve macrophage polarization toward an M1 phenotype. Among the anti-inflammatory molecules, the production of indoleamine 2,3-dioxygenase (IDO) and nitric oxide synthase 2 (NOS2) was profoundly increased, whereas cyclooxygenase-2 (COX-2) was decreased in the XF-MSCs. Finally, the XF-MSCs had an enhanced therapeutic effect against mouse experimental colitis. These findings indicate that xeno-free culture conditions improved the immunomodulatory properties of WJ-MSCs and ex vivo-expanded XF-MSCs might be an effective strategy for preventing the progression of colitis. Full article