Journal of Clinical Medicine — Open Access Journal

Secondary hemophagocytic lymphohistiocytosis (sHLH) is a life-threatening condition clinically presenting as SIRS (Systemic Inflammatory Response Syndrome). However, there is no comprehensive data concerning diagnostic algorithms, prevalence, outcome and biomarker performance in SIRS patients. We conducted a prospective observational cohort study on 451 consecutive patients fulfilling ≥2 SIRS criteria. The Hscore and the HLH-2004 criteria were used to determine the presence of sHLH, and the correlation of the screening-biomarkers ferritin, sCD25, and sCD163 with both scores was assessed. Out of 451 standard-care SIRS patients, five patients had high Hscores (≥169), suggesting incipient or HLH-like disease, and these patients were in urgent need for intensified therapy. However, none of these patients fulfilled five HLH-2004 criteria required for formal diagnosis. From the studied biomarkers, ferritin correlated strongest to both the HLH-2004 criteria and the Hscore (rs = 0.72, 0.41, respectively), and was the best predictor of 30-day survival (HR:1.012 per 100 μg/L, 95% CI: 1.004–1.021), when adjusted for patient’s age, sex, bacteremia and malignant underlying-disease. Also, the HLH-2004 (HR per point increase: 1.435, 95% CI: 1.1012–2.086) and the Hscore (HR per point increase:1.011, 95% CI: 1.002–1.020) were independent predictors of 30-day-survival. The Hscore detected patients in hyperinflammatory states requiring urgent therapy escalation. Degrees of hyperinflammation, as assessed by ferritin and both HLH scores, are associated with worse outcomes. Full article

Association of celiac disease (CD) with systemic autoimmune diseases (ADs) remains controversial. Awareness of CD in these patients is important to prevent complications, including lymphoproliferative disorders. We evaluated previously diagnosed CD prevalence in systemic lupus erythematosus (SLE), primary Sjögren’s syndrome (pSS) and systemic sclerosis (SSc) patients in comparison to 14,298 matched controls. All patients were screened for subclinical CD. Data from 1458 unselected consecutive SLE (580), pSS (354) and SSc (524) patients were collected. Previously biopsy-proven CD diagnosis and both CD- and AD-specific features were registered. All patients without previous CD were tested for IgA transglutaminase (TG). Anti-endomysium were tested in positive/borderline IgA TG. Duodenal biopsy was performed in IgA TG/endomysium+ to confirm CD. CD prevalence in AD was compared to that observed in 14,298 unselected sex- and age-matched adults who acted as controls. CD was more prevalent in pSS vs controls (6.78% vs 0.64%, p < 0.0001). A trend towards higher prevalence was observed in SLE (1.38%, p = 0.058) and SSc (1.34%, p = 0.096). Higher CD prevalence was observed in diffuse cutaneous SSc (4.5%, p ≤ 0.002 vs controls). Subclinical CD was found in two SLE patients and one pSS patient. CD diagnosis usually preceded that of AD. Primary SS and SSc–CD patients were younger at AD diagnosis in comparison to non-celiac patients. Autoimmune thyroiditis was associated with pSS and CD. CD prevalence is clearly increased in pSS and diffuse SSc in comparison to the general population. The association of CD with diffuse but not limited SSc may suggest different immunopathogenic mechanisms characterizing the two subsets. CD screening may be considered in pSS and diffuse SSc in young patients, particularly at the time of diagnosis. Full article

Extranasal cancers that metastasize to the sinonasal cavity are very rare. To date, there are only limited reports regarding this rare condition within the literature. Therefore, we retrospectively reviewed all patients diagnosed with metastatic cancer of the sinonasal tract from 2003 to 2018 at a tertiary academic medical center. Patient demographic data, clinical presentation, treatment modalities, and outcomes were investigated. There were a total of 17 patients (9 males and 8 females) included in the analysis. The mean age was 56.8 years (range 27–80). The most common primary malignancies were hepatocellular carcinoma (n = 3) and gastrointestinal tract adenocarcinoma (n = 3). The most common site of metastasis was the nasal cavity (n = 8). Five patients received radical tumor resection and the others underwent radiotherapy, chemotherapy, or combined chemoradiotherapy. The 2-year survival was 28%. In summary, metastasis to the sinonasal cavity remains extremely rare. A high degree of suspicion regarding the possibility of metastatic spread to the sinonasal region is necessary for patients with a previous history of malignancy who present with new sinonasal symptoms. The treatment strategy of sinonasal metastatic cancer is usually palliative therapy and the prognosis remains poor. However, early detection and diagnosis, coupled with aggressive treatment, may improve patient quality of life. Full article

The aim of this study was to determine the association between radiologic spinal pathology and the response to medial branches block (MBB). This retrospective observational study compared 165 patients. A successful response was defined as ≥30% or a 2-point reduction in the numeric rating scale (NRS) compared with the baseline at the 1-month follow-up. The facet angle, facet angle difference, facet joint degeneration, disc height and spondylolisthesis grade were analyzed from an MRI at the L3 to S1 levels. Univariate and multivariate logistic regression analyses were used to evaluate independent factors associated with a successful response of MBB. In the univariate analysis, the disc height at L5–S1 and facet angle difference at L3–4 were lower in the positive responders (p = 0.022 and p = 0.087, respectively). In the multivariate analysis, the facet angle difference at L3–4 and disc height at L5–S1 were independent factors associated with a successful response (odds ratio = 0.948; p = 0.038 and odds ratio = 0.864; p = 0.038, respectively). In patients with a degenerative disc at L5–S1, MBB can lead to a good response for at least one month. In patients with facet tropism at L3–4 level, the response to MBB after one month is likely to be poor. Full article

Stroke-induced hypoxia causes oligodendrocyte death due to inflammation, lack of oxygen and exacerbation of cell death. Bone marrow-derived stem cells (BMSCs) possess an endogenous population of T-regulatory cells (T_regs) which reduce secretion of pro-inflammatory cytokines that lead to secondary cell death. Here, we hypothesize that oligodendrocyte progenitor cells (OPCs) cultured with BMSCs containing their native T_reg population show greater cell viability, less pro-inflammatory cytokine secretion and greater myelin production after exposure to oxygen-glucose deprivation and reoxygenation (OGD/R) than OPCs cultured without T_regs. OPCs were cultured and then exposed to OGD/R. BMSCs with or without T_regs were added to the co-culture immediately after ischemia. The T_regs were depleted by running the BMSCs through a column containing a magnetic substrate. Fibroblast growth factor beta (FGF-β) and interleukin 6 (IL-6) ELISAs determined BMSC activity levels. Immunohistochemistry assessed OPC differentiation. OPCs cultured with BMSCs containing their endogenous T_regs showed increased myelin production compared to the BMSCs with depleted T_regs. IL-6 and FGF-β were increased in the group cultured with T_regs. Collectively, these results suggest that BMSCs containing T_regs are more therapeutically active, and that T_regs have beneficial effects on OPCs subjected to ischemia. T_regs play an important role in stem cell therapy and can potentially treat white matter injury post-stroke. Full article

The purpose of the present systematic review and meta-analysis was to explore the effects of transcranial direct current stimulation (tDCS) on endurance (i.e., time to task failure (TTF)) and maximal voluntary contraction (MVC). Furthermore, we aimed to analyze whether the duration of stimulation, the brain region targeted for stimulation, and the task performed could also influence motor performance. We performed a systematic literature review in the databases MEDLINE and Web of Science. The short-term effects of anodal tDCS and sham stimulation (placebo) were considered as experimental and control conditions, respectively. A total of 31 interventions were included (MVC = 13; TTF = 18). Analysis of the strength-related tDCS studies showed small improvements in the MVC (SMD = 0.19; 95% CI = −0.02, 0.41; p = 0.08). However, the results of the endurance-related interventions indicated a moderate effect on TTF performance (SMD = 0.26; 95% CI = 0.07, 0.45; p = 0.008). Furthermore, the sub-analysis showed that anodal tDCS over M1 and stimulation durations longer than 10 min produced the best results in terms of TTF performance enhancement. Additionally, the effects of anodal tDCS were larger during full body exercises (i.e., cycling) when compared to uniarticular tasks. In conclusion, the current meta-analysis indicated that anodal tDCS leads to small and moderate effects on MVC and TTF, respectively. Full article

The prevalence, relationships and outcomes of sarcopenia and frailty in polypathological patients remain unknown. We performed a multicenter prospective observational study in six hospitals in order to assess prevalence, clinical features, outcome and associated risk factors of sarcopenia and frailty in a hospital-based population of polypathological patients. The cohort was recruited by performing prevalence surveys every 14 days during the inclusion period (March 2012–June 2016). Sarcopenia was assessed by means of EWGSOP criteria and frailty by means of Fried’s criteria. Skeletal muscle mass was measured by tetrapolar bioimpedanciometry. All patients were followed for 12 months. Factors associated with sarcopenia, frailty and mortality were analyzed by multivariate logistic regression, and Kaplan–Meier curves. A total of 444 patients (77.3 ± 8.4 years, 55% males) were included. Sarcopenia was present in 97 patients (21.8%), this being moderate in 54 (12.2%), and severe in 43 (9.6%); frailty was present in 278 patients (62.6%), and 140 (31.6%) were pre-frail; combined sarcopenia and frailty were present in the same patient in 80 (18%) patients. Factors independently associated to the presence of both, sarcopenia and frailty were female gender, older age, different chronic conditions, poor functional status, low body mass index, asthenia and depressive disorders, and low leucocytes and lymphocytes count. Mortality in the 12-months follow-up period was 40%. Patients with sarcopenia, frailty or both survived significantly less than those without these conditions. Sarcopenia and frailty are frequent and interrelated conditions in polypathological patients, shadowing their survival. Their early recognition and management could improve health-related outcomes in this population. Full article

Patients with serious psychiatric diseases (major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia and psychotic disorder) often complain about sleepiness during the day, fatigue, low energy, concentration problems, and insomnia; unfortunately, many of these symptoms are also frequent in patients with Obstructive Sleep Apnea (OSA). However, existing data about the clinical appearance of OSA in Psychiatric Disease are generally missing. The aim of our study was a detailed and focused evaluation of OSA in Psychiatric Disease, in terms of symptoms, comorbidities, clinical characteristics, daytime respiratory function, and overnight polysomnography data. We examined 110 patients (56 males and 54 females) with stable Psychiatric Disease (Group A: 66 with MDD, Group B: 34 with BD, and Group C: 10 with schizophrenia). At baseline, each patient answered the STOP–Bang Questionnaire, Epworth Sleepiness Scale (ESS), Fatigue Severity Scale (FSS), and Hospital Anxiety and Depression Scale (HADS) and underwent clinical examination, oximetry, spirometry, and overnight polysomnography. Body Mass Index (BMI), neck, waist, and hip circumferences, and arterial blood pressure values were also measured. The mean age of the whole population was 55.1 ± 10.6 years. The three groups had no statistically significant difference in age, BMI, hip circumference, and systolic and diastolic arterial blood pressure. Class II and III obesity with BMI > 35 kg/m² was observed in 36 subjects (32.14%). A moderate main effect of psychiatric disease was observed in neck (p = 0.044, η² = 0.064) and waist circumference (p = 0.021, η² = 0.078), with the depression group showing the lowest values, and in pulmonary function (Forced Vital Capacity (FVC, %), p = 0.013, η² = 0.084), with the psychotic group showing the lowest values. Intermediate to high risk of OSA was present in 87.37% of participants, according to the STOP–Bang Questionnaire (≥3 positive answers), and 70.87% responded positively for feeling tired or sleepy during the day. An Apnea–Hypopnea Index (AHI) ≥ 15 events per hour of sleep was recorded in 72.48% of our patients. AHI was associated positively with male sex, schizophrenia, neck, and waist circumferences, STOP–Bang and ESS scores, and negatively with respiratory function. A large main effect of psychiatric medications was observed in waist circumference (p = 0.046, η² = 0.151), FVC (%) (p = 0.027, η² = 0.165), and in time spend with SaO₂ < 90% (p = 0.006, η² = 0.211). Our study yielded that patients with Psychiatric Disease are at risk of OSA, especially men suffering from schizophrenia and psychotic disorders that complain about sleepiness and have central obesity and disturbed respiratory function. Screening for OSA is mandatory in this medical population, as psychiatric patients have significantly poorer physical health than the general population and the coexistence of the two diseases can further negatively impact several health outcomes. Full article

The aim of this study was to determine the optimal preconditioning regimen for the wound healing therapeutic efficacy of mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs). To this end, we compared various preconditioning regimens for both the quantitative and qualitative production of MSC-derived EVs, and their therapeutic efficacy for proangiogenic activity in vitro and cutaneous wound healing in vivo. After preconditioning with thrombin (40 U), H₂O₂ (50 μM), lipopolysaccharide (1 μg/mL), or hypoxia (10% O₂), EV secretion was assessed quantitatively by measuring production per cell and protein quantification, and qualitatively by measuring a proteome profiler and an enzyme-linked immunosorbent assay (ELISA) contained within EVs. The therapeutic efficacy of EVs was assessed in vitro by proliferation, migration and tube formation assays of human umbilical cord blood endothelial cells (HUVECs), and in vivo by quantification of cutaneous wound healing. Thrombin preconditioning optimally boosted EV production and enriched various growth factors including vascular endothelial growth factor and angiogenin contained within EVs compared to other preconditioning regimens. Thrombin preconditioning optimally enhanced proliferation, the migration and tube formation of HUVECs in vitro via pERK1/2 and pAKT signaling pathways, and cutaneous wound healing in vivo compared to other preconditioning regimens. Thrombin preconditioning exhibited optimal therapeutic efficacy compared with other preconditioning regimens in promoting proangiogenic activity in vitro and in enhancing cutaneous wound healing in vivo. These preconditioning regimen-dependent variations in therapeutic efficacy might be mediated by boosting EV production and enriching their cargo content. Full article

Hidradenitis suppurativa (HS) is a chronic auto-inflammatory skin disease with a great impact in quality of life. However, there is little research about the impact of HS on sex life. The aims of this study are to describe the frequency of sexual distress (SD) in patients with HS and to explore potentially associated epidemiological and clinical factors. We conducted a cross-sectional study by means of a crowd-sourced online questionnaire hosted by the Spanish hidradenitis suppurativa patients’ association (ASENDHI). Sexual distress (SD) was evaluated with a Numeric Rating Scale (NRS) for HS impact on sex life. A total of 393 participants answered the questionnaire. The mean NRS for HS impact on sex life was 7.24 (2.77) in women and 6.39 (3.44) in men (p < 0.05). Variables significantly associated (p < 0.05) with SD in the multiple linear regression model were sex, with a higher risk in females, the presence of active lesions in the groin and genitals and NRS for pain and unpleasant odor; being in a stable relationship was an important protector factor. Regarding these results, it seems that SD in HS patients is due, at least in part, to disease symptoms and active lesions in specific locations, emphasizing the importance of disease control with a proper treatment according to management guidelines. Women and single patients are more likely to suffer from sexual distress. Full article

Physical activity (PA) interventions can improve physical functioning, treatment-related symptoms and quality of life (QoL) in cancer survivors. Most investigations have been conducted in breast cancer survivors, while studies on PA interventions in gynecological cancer survivors are scant. Here, we report for the first time the possible benefits of a structured PA pathway (i.e., eight weeks of adapted PA followed by twelve weeks of adapted fitness) on physical side effects, pain and QoL in an uncommon case of survivorship of both primary breast and gynecological cancers. For this purpose, a 69-year-old woman was assessed by functional test battery (shoulder–arm mobility, range of motion, back flexibility) at baseline and after the structured PA pathway. QoL and surgical shoulder, back and lower limb pain intensity were evaluated by Short Form-12 (SF-12) and numerical rating scale questionnaires, respectively. Lower limb circumference was also assessed. Improvement in upper limb function, reduction of lower limb edema and pain perception, as well as an increase in overall QoL were achieved after the completion of structured PA intervention. Our findings suggest that a PA intervention tailored to individual characteristics may represent an effective countermeasure to reduce post-treatment functional disability and pain, and thus to improve QoL in breast and gynecologic cancer survivors. Full article

Background: The incidence and mortality of renal cell carcinoma (RCC) after kidney transplantation (KTx) remain unclear. This study's aims were (1) to investigate the pooled incidence/incidence trends, and (2) to assess the mortality/mortality trends in KTx patients with RCC. Methods: A literature search was conducted using the MEDLINE, EMBASE and Cochrane databases from inception through October 2018. Studies that reported the incidence or mortality of RCC among kidney transplant recipients were included. The pooled incidence and 95% CI were calculated using a random-effect model. The protocol for this meta-analysis is registered with PROSPERO; no. CRD42018108994. Results: A total of 22 observational studies with a total of 320,190 KTx patients were enrolled. Overall, the pooled estimated incidence of RCC after KTx was 0.7% (95% CI: 0.5–0.8%, I² = 93%). While the pooled estimated incidence of de novo RCC in the native kidney was 0.7% (95% CI: 0.6–0.9%, I² = 88%), the pooled estimated incidence of RCC in the allograft kidney was 0.2% (95% CI: 0.1–0.4%, I² = 64%). The pooled estimated mortality rate in KTx recipients with RCC was 15.0% (95% CI: 7.4–28.1%, I² = 80%) at a mean follow-up time of 42 months after RCC diagnosis. While meta-regression analysis showed a significant negative correlation between year of study and incidence of de novo RCC post-KTx (slopes = −0.05, P = 0.01), there were no significant correlations between the year of study and mortality of patients with RCC (P = 0.50). Egger's regression asymmetry test was performed and showed no publication bias in all analyses. Conclusions: The overall estimated incidence of RCC after KTX was 0.7%. Although there has been a potential decrease in the incidence of RCC post-KTx, mortality in KTx patients with RCC has not decreased over time. Full article

Tumor recurrence is frequent and survival rates remain extremely low in lung adenocarcinoma (ADC). We hypothesize that carcinogenic factors will promote loco-regional modifications not only in the future tumor, but throughout the exposed lung. Objective: To analyze whether the most prevalent mutations observed in ADC can also be observed in the non-neoplastic lung tissue, as well as the short-term prognosis implications of this finding. Methods: Non-tumoral lung parenchyma specimens obtained during surgery from 47 patients with EGFR and/or KRAS abnormalities in their ADC tumors underwent similar genomic testing. Short-term outcomes were also recorded. Results: The same mutations were present in the tumor and the histologically normal tissue in 21.3% of patients (SM group). Although local recurrences were similar in both groups, distant metastases were more frequent in the former (60 vs. 5.4%, p < 0.001). Moreover, SM patients showed lower time-to-progression (8.5 vs. 11.7 months, p < 0.001) and disease-free survival (8.5 vs. 11.2 months, p < 0.001). COX regression showed a higher risk of progression or death (DFS) in the SM group (HR 5.94, p < 0.01]. Similar results were observed when adjusting for potential confounding variables. Conclusions: These results confirm that genetic changes are present in the apparently normal lung in many ADC patients, and this finding has prognostic implications. Full article

Background: Fabry disease (FD) is a X-linked recessive lysosomal storage disorder characterized by altered biodegradation of glycosphingolipids. It is a multisystem pathology, also involving ophthalmological systems that show modifications of the vessel wall due to glycosphingolipid deposits. Optical coherence tomography angiography (OCT-A) allows for an objective analysis of retinal microvasculature alterations, evaluating retinal vessel density in macular region. Methods: A total of 54 FD patients (34 females, 20 males, mean age 44.1 ± 15.6 years) and 70 controls (36 females, 34 males, mean age 42.3 ± 15.6 years) were included in this study. We evaluated vessel density in different macular areas (whole image, fovea, and parafovea) of both the superficial capillary plexus (SCP) and of the deep capillary plexus (DCP). Results: In the SCP there was a significantly lower vascular density in patients compared with controls in whole image (49.95 ± 5.17% vs. 51.99 ± 2.52%; p < 0.001), parafovea (52.01 ± 6.69% vs. 54.30 ± 2.61%; p = 0.002), and fovea (22.38 ± 9.01% vs. 29.31 ± 5.84%; p < 0.0001). In the DCP the vessel density was statistically increased in each macular area in patients compared with controls (54.82 ± 8.07% vs. 50.93 ± 5.46%; p = 0.005, 57.76 ± 7.26% vs. 53.59 ± 5.46%; p = 0.0001, and 39.75 ± 8.59% vs. 34.43 ± 8.68%; p < 0.0001 for whole image, parafovea, and fovea, respectively). Conclusion: OCT-A analysis showed that the macular vessel density was significantly reduced in the SCP and increased in the DCP in FD patients compared with controls. These findings, which might be a consequence of the alteration of vascular wall occurring in FD, support the hypothesis that the evaluation of early retinal microvascular network changes could be a useful tool in the clinical evaluation of the disease. Full article

Rates of adverse cardiovascular events have increased among middle-aged adults. Elevated ceramides have been proposed as a risk factor for cardiovascular events. Diet quality and weight status are inversely associated with several traditional risk factors; however, the relationship to ceramides is less clear. This study aimed to determine associations of adiposity and diet quality with circulating ceramides in middle-aged adults (n = 96). Diet quality was estimated using the Healthy Eating Index 2015 (HEI-2015). Serum ceramide concentrations were determined by liquid chromatography–mass spectrometry. A ceramide risk score was determined based on ceramides C16:0, C18:0, and C24:1 and their ratios to C24:0. Participants who were classified as at ‘moderate risk’ compared to ‘lower-risk’ based on a ceramide risk score had significantly higher body mass index (BMI) values, as well as higher rates of elevated fibrinogen levels, metabolic syndrome, and former smoking status. BMI was positively associated with the ceramide C18:0 (R² = 0.31, p < 0.0001), the ratio between C18:0/C24:0 ceramides (R² = 0.30, p < 0.0001), and the ceramide risk score (R² = 0.11, p < 0.009). Total HEI-2015 scores (R² = 0.42, p = 0.02), higher intakes of vegetables (R² = 0.44, p = 0.02) and whole grains (R² = 0.43, p = 0.03), and lower intakes of saturated fats (R² = 0.43, p = 0.04) and added sugar (R² = 0.44, p = 0.01) were associated with lower C22:0 values. These findings suggest that circulating ceramides are more strongly related to adiposity than overall diet quality. Studies are needed to determine if improvements in weight status result in lower ceramides and ceramide risk scores. Full article

Objective: To identify echocardiographic and surgical risk factors for failure after mitral valve repair. Methods: We identified a total of 77 consecutive patients from our institutional mitral valve surgery database who required redo mitral valve surgery due to recurrence of mitral regurgitation after primary mitral valve repair. A control group of 138 patients who had a stable echocardiographic long-term result was included based on propensity score matching. Systematic analysis of echocardiographic parameters was performed before primary surgery; after mitral valve repair and prior to redo surgery. Risk factor analysis was performed using multivariate Cox regression model. Results: Redo surgery was associated with the presence of pulmonary hypertension ≥ 50 mmHg (p = 0.02), a mean transmitral gradient > 5 mmHg (p = 0.001), left ventricular ejection fraction ≤ 45% (p = 0.05) before surgery and mitral regurgitation ≥moderate at time of discharge (p = 0.002) in the whole cohort. Patients with functional mitral valve regurgitation had a higher tendency to undergo redo surgery if preoperative left ventricular end-diastolic diameter exceeded 65 mm (p = 0.043) and if postoperative tenting height exceeded 6 mm (p = 0.018). Low ejection fraction was not significantly associated with the need for redo mitral valve surgery in the functional subgroup. Conclusions: Recurrent mitral regurgitation is still a valuable problem and is associated with relevant perioperative mortality. Patients with severe mitral regurgitation should undergo early mitral valve repair surgery as long as systolic pulmonary artery pressure is low, left ventricular ejection fraction is preserved, and LVEED is deceeds 65 mm. Full article

The healing of venous and arterial ulcers is slow, and in some cases, they may not heal at all. This study aims to demonstrate the clinical advantage of Nevelia^®, an innovative collagen dermal template substitute (DS) in venous and arterial chronic ulcers treatment. 35 patients affected by chronic vascular ulcers with a mean area of 35.1 ± 31.8 cm² were treated with DS followed by autologous dermal epidermal graft (DEG). Follow-up was performed at 7-14-21 and 28 days after DS implant and 7-14-21 and 28 days after DEG. At 28 days after DEG, the mean values of Manchester Scar Scale was of 1.8 ± 0.7 for skin color, 1.6 ± 0.7 for skin contour, 1.7 ± 0.7 for distortion, and 1.7 ± 0.7 for skin texture, whereas skin was matte in 27 patients (77%) and shiny in the remaining eight cases (23%). Histological findings correlate with the clinical result showing a regenerated skin with reactive epidermal hyperplasia and dermal granulation tissue after two weeks (T1), and after three weeks (T2) a re-epithelialization and a formed new tissue architecture analogue to normal skin physiology. These data suggest that Nevelia^® could be useful to treat chronic venous and arterial ulcers. Full article

Background: This study aimed to evaluate the hospitalization rates for subarachnoid hemorrhage (SAH) among renal transplant patients with adult polycystic kidney disease (ADPKD) and its outcomes, when compared to non-ADPKD renal transplant patients. Methods: The 2005–2014 National Inpatient Sample databases were used to identify all hospitalized renal transplant patients. The inpatient prevalence of SAH as a discharge diagnosis between ADPKD and non-ADPKD renal transplant patients was compared. Among SAH patients, the in-hospital mortality, use of aneurysm clipping, hospital length of stay, total hospitalization cost and charges between ADPKD and non-ADPKD patients were compared, adjusting for potential confounders. Results: The inpatient prevalence of SAH in ADPKD was 3.8/1000 admissions, compared to 0.9/1000 admissions in non-ADPKD patients (p < 0.01). Of 833 renal transplant patients with a diagnosis of SAH, 30 had ADPKD. Five (17%) ADPKD renal patients with SAH died in hospitals compared to 188 (23.4%) non-ADPKD renal patients (p = 0.70). In adjusted analysis, there was no statistically significant difference in mortality, use of aneurysm clipping, hospital length of stay, or total hospitalization costs and charges between ADPKD and non-ADPKD patients with SAH. Conclusion: Renal transplant patients with ADPKD had a 4-fold higher inpatient prevalence of SAH than those without ADPKD. Further studies are needed to compare the incidence of overall admissions in ADPKD and non-ADPKD patients. When renal transplant patients developed SAH, inpatient mortality rates were high regardless of ADPKD status. The outcomes, as well as resource utilization, were comparable between the two groups. Full article

Erythroferrone (ERFE) is a hepcidin inhibitor whose synthesis is stimulated by erythropoietin, which increases iron absorption and mobilization. We studied the association between serum ERFE and mortality and non-fatal cardiovascular (CV) events in a cohort of 1123 hemodialysis patients and in a cohort of 745 stage 1–5 chronic kidney disease (CKD) patients. Erythroferrone was measured by a validated enzyme-linked immunosorbent assay (ELISA). In the hemodialysis cohort, serum ERFE associated directly with erythropoiesis stimulating agents (ESA) dose (p < 0.001) and inversely with serum iron and ferritin (p < 0.001). Erythroferrone associated with the combined outcome in an analysis adjusting for traditional risk factors, factors peculiar to end-stage kidney disease, serum ferritin, inflammation, and nutritional status (HR, hazard ratio, (5 ng/mL increase: 1.04, 95% confidence interval, CI: 1.01–1.08, p = 0.005). Furthermore, treatment with ESA modified the relationship between ERFE and the combined end-point in adjusted analyses (p for the effect modification = 0.018). Similarly, in CKD patients there was a linear increase in the risk for the same outcome in adjusted analyses (HR (2 ng/mL increase): 1.04, 95% CI: 1.0–1.07, p = 0.015). Serum ERFE is associated with mortality and CV events in CKD and in HD patients, and treatment by ESA amplifies the risk for this combined end-point in HD patients. Full article