Table of Contents

The current study explores the antimycobacterial efficacy of lichen-derived psoromic acid (PA) against clinical strains of Mycobacterium tuberculosis (M.tb). Additionally, the inhibitory efficacy of PA against two critical enzymes associated with M.tb, namely, UDP-galactopyranose mutase (UGM) and arylamine-N-acetyltransferase (TBNAT), as drug targets for antituberculosis therapy were determined. PA showed a profound inhibitory effect towards all the M.tb strains tested, with minimum inhibitory concentrations (MICs) ranging between 3.2 and 4.1 µM, and selectivity indices (SIs) ranging between 18.3 and 23.4. On the other hand, the standard drug isoniazid (INH) displayed comparably high MIC values (varying from 5.4 to 5.8 µM) as well as low SI values (13.0–13.9). Interestingly, PA did not exhibit any cytotoxic effects on a human liver hepatocellular carcinoma cell line even at the highest concentration tested (75 µM). PA demonstrated remarkable suppressing propensity against UGM compared to standard uridine-5'-diphosphate (UDP), with 85.8 and 99.3% of inhibition, respectively. In addition, PA also exerted phenomenal inhibitory efficacy (half maximal inhibitory concentration (IC₅₀) value = 8.7 µM, and 77.4% inhibition) against TBNAT compared with standard INH (IC₅₀ value = 6.2 µM and 96.3% inhibition). Furthermore, in silico analysis validated the outcomes of in vitro assays, as the molecular interactions of PA with the active sites of UGM and TBNAT were unveiled using molecular docking and structure–activity relationship studies. Concomitantly, our findings present PA as an effective and safe natural drug plausible for use in controlling tuberculosis infections. Full article

IgA nephropathy is an autoimmune disease induced by fthe ormation of galactose-deficient IgA1 and anti-glycans autoantibody. A multi-hit hypothesis was promoted to explain full expression of IgA nephropathy. The deposition of immune complex resulted in activation of the complement, increasing oxidative stress, promoting inflammatory cascade, and inducing cell apoptosis via mesangio-podocytic-tubular crosstalk. The interlinked signaling pathways of immune-complex-mediated inflammation can offer a novel target for therapeutic approaches. Treatments of IgA nephropathy are also summarized in our review article. In this article, we provide an overview of the recent basic and clinical studies in cell molecular regulation of IgAN for further treatment interventions. Full article

Objectives: Interactions between mechanical ventilation (MV) and carbapenem interventions were investigated for the risk of Clostridium difficile infection (CDI) in critically ill patients undergoing concurrent carbapenem therapy. Methods: Taiwan’s National Intensive Care Unit Database (NICUD) was used in this analytical, observational, and retrospective study. We analyzed 267,871 intubated patients in subgroups based on the duration of MV support: 7–14 days (n = 97,525), 15–21 days (n = 52,068), 22–28 days (n = 35,264), and 29–60 days (n = 70,021). The primary outcome was CDI. Results: Age (>75 years old), prolonged MV assistance (>21 days), carbapenem therapy (>15 days), and high comorbidity scores were identified as independent risk factors for developing CDI. CDI risk increased with longer MV support. The highest rate of CDI was in the MV 29–60 days subgroup (adjusted hazard ratio (AHR) = 2.85; 95% confidence interval (CI) = 1.46–5.58; p < 0.02). Moreover, higher CDI rates correlated with the interaction between MV and carbapenem interventions; these CDI risks were increased in the MV 15–21 days (AHR = 2.58; 95% CI = 1.12–5.91) and MV 29–60 days (AHR = 4.63; 95% CI = 1.14–10.03) subgroups than in the non-MV and non-carbapenem subgroups. Conclusions: Both MV support and carbapenem interventions significantly increase the risk that critically ill patients will develop CDI. Moreover, prolonged MV support and carbapenem therapy synergistically induce CDI. These findings provide new insights into the role of MV support in the development of CDI. Full article

Continuous monitoring of the fetal heart rate (FHR) signal has been widely used to allow obstetricians to obtain detailed physiological information about newborns. However, visual interpretation of FHR traces causes inter-observer and intra-observer variability. Therefore, this study proposed a novel computerized analysis software of the FHR signal (CAS-FHR), aimed at providing medical decision support. First, to the best of our knowledge, the software extracted the most comprehensive features (47) from different domains, including morphological, time, and frequency and nonlinear domains. Then, for the intelligent assessment of fetal state, three representative machine learning algorithms (decision tree (DT), support vector machine (SVM), and adaptive boosting (AdaBoost)) were chosen to execute the classification stage. To improve the performance, feature selection/dimensionality reduction methods (statistical test (ST), area under the curve (AUC), and principal component analysis (PCA)) were designed to determine informative features. Finally, the experimental results showed that AdaBoost had stronger classification ability, and the performance of the selected feature set using ST was better than that of the original dataset with accuracies of 92% and 89%, sensitivities of 92% and 89%, specificities of 90% and 88%, and F-measures of 95% and 92%, respectively. In summary, the results proved the effectiveness of our proposed approach involving the comprehensive analysis of the FHR signal for the intelligent prediction of fetal asphyxia accurately in clinical practice. Full article

The behavioral inhibition/activation systems (BIS/BAS) have been considered to be predictors of Internet addiction, mediated by clinical variables such as anxiety and depression. However, resilience has been suggested as a protective factor toward Internet addiction, and certain sex differences in resilience buffering the effects of vulnerability have been reported. Thus, the aim of this study was to identify any role of resilience that might moderate the effects of BIS/BAS on Internet addiction through multiple clinical variables in boys and girls. A total of 519 middle-school students (268 boys and 251 girls, all 14 years old) were administered a questionnaire battery that measures Internet addiction, BIS/BAS, depression, anxiety, impulsivity, anger, and resilience. We used the PROCESS macro in SPSS to perform moderation and mediation analysis. Findings revealed that although a somewhat similar mediation model was supported in both sexes, moderating effects of resilience only emerged in girls. The results showed a protective role of resilience differing between sexes. These results suggest that clinicians should consider sex in the way resilience works as a protective factor against Internet addiction and focus on mitigating the effects of vulnerability by enhancing resilience in female Internet addicts. Full article

A monoclonal gammopathy of undetermined significance (MGUS) may develop into a multiple myeloma or a correlated lymphoproliferative malignancy with a progress rate of 1% per year. The immune status, occupational-environmental risk factors, and hereditary factors may influence the risk of developing MGUS. We investigated the prevalence of MGUS in 77 refinery waste workers. They were all males, averagely aged 36, with a mean working history of 18.5 years and working in the dump for about 4.2 years. After analyzing the results of standard serum electrophoresis migrations, 16% of cases (n = 12) showed levels beyond the normal ranges. In all 12 samples we observed an increase of gamma component: 67%, IgG; 17%, IgM; 8%, IgA; 8%, oligoclonal. Workers were exposed to hazardous refinery waste. After the biological monitoring of urine samples for metals and t,t-muconic acid, no extra-range values were observed. The multivariate analysis shows, however, that cigarette smoking and residence near industrial sites are significantly (p < 0.001) associated with a high risk of MGUS development; while no association was found with occupational exposure. Additional attention might be paid in particular to these conditions in epidemiological studies and further larger, prospective, population-based researches appear warranted to evaluate the strength of any positive association. Full article

The association between mitochondrial DNA (mtDNA) haplogroup and risk of type 2 diabetes (T2D) is undetermined and controversial. This study aims to evaluate the impact of the main mtDNA haplogroups on glycaemic control and renal function in a Spanish population of 303 T2D patients and 153 healthy controls. Anthropometrical and metabolic parameters were assessed and mtDNA haplogroup was determined in each individual. Distribution of the different haplogroups was similar in diabetic and healthy populations and, as expected, T2D patients showed poorer glycaemic control and renal function than controls. T2D patients belonging to the JT haplogroup (polymorphism m.4216T>C) displayed statistically significant higher levels of fasting glucose and HbA_1c than those of the other haplogroups, suggesting a poorer glycaemic control. Furthermore, diabetic patients with the JT haplogroup showed a worse kidney function than those with other haplogroups, evident by higher levels of serum creatinine, lower estimated glomerular filtration rate (eGFR), and slightly higher (although not statistically significant) urinary albumin-to-creatinine ratio. Our results suggest that JT haplogroup (in particular, change at position 4216 of the mtDNA) is associated with poorer glycaemic control in T2D, which can trigger the development of diabetic nephropathy. Full article

Noninvasive simple scores have been validated to assess advanced liver fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). We performed a systematic review with meta-analysis evaluating if NAFLD fibrosis score (NFS), AST to platelet ratio index (APRI), and Fibrosis-4 (FIB-4) score may also predict mortality. PubMed and EMBASE databases were searched until April 2018. Random-effects models were used to calculate pooled RRs of mortality for highest vs. lowest categories of exposure and to perform dose-response meta-analysis. Heterogeneity was assessed using the Q test and I² statistic. Overall, eight studies were included in the systematic review; all of the eight studies provided data for NFS, while four provided data for APRI and FIB-4. When comparing the risk estimates for high (>0.676) vs. intermediate + low NFS (≤0.676), we found a nearly fourfold increase in mortality risk, with evidence of heterogeneity (RR = 3.85, 95% CI: 2.08, 7.11; I² = 92%). At dose-response meta-analysis, compared to the midpoint of the lowest category of NFS (−2.5), the risk of mortality was about twofold higher for NFS = −0.5 (RR = 2.20, 95% CI: 1.31, 3.70) and more than fivefold higher for NFS = 1.5 (RR = 5.16, 95% CI: 2.02, 13.16). When comparing the risk estimates for high (>1.5) vs. medium + low APRI (≤1.5), we found a higher risk of mortality, without heterogeneity (RR = 3.61, 95% CI: 1.79, 7.28; I² = 0%). Comparison of the risk estimates for high (>2.67) vs. medium + low FIB-4 (≤2.67) didn’t reveal a significantly higher risk of mortality, with heterogeneity (RR = 2.27, 95% CI: 0.72, 7.15; I² = 85%). Dose-response analysis for APRI and FIB-4 was not considered conclusive due to the low number of studies. Based on the results of our meta-analysis, the measurement of NFS can be considered an accurate tool for the stratification of the risk of death in patients with NAFLD. Full article

Primary prostatic signet ring cell carcinoma is a rare form of cancer with a poor prognosis, which is generally treated with a traditional prostate adenocarcinoma therapy. This case report presents a 70-year-old diagnosed with primary prostatic signet ring cell carcinoma, treated with a combination of radiotherapy and hormone therapy and a 16 month survival without an evidence of the disease at follow up. Full article

Objective: The aims of our study were to translate the dysfunctional voiding symptom score (DVSS) from English to Serbian; culturally adopt the items; assess the internal consistency and the test–retest reliability of DVSS_SR in patients with dysfunctional voiding (DV); evaluate and test the construct and divergent validity of DVSS_SR against demographic parameters (gender and education); and examine the level of explained variability for each item of DVSS_SR against demographic parameters (gender and education). Methods: The cross-sectional observational study included 50 patients with dysfunctional voiding aged 5 years and above. The DVSS questionnaire was translated from English into Serbian by the forward–backward method. Internal consistency was assessed with Cronbach α and test–retest reliability with intraclass correlation coefficient (ICC). For validity testing we performed construct and divergent validity analyses. Results: There was excellent internal consistency for every item except for Item 6 (0.787) and Item 3 (0.864), where internal consistency was good. The observed test/retest ICC for average measures was more than 0.75 (excellent) for all DVSS_SR items. Gender and educational level does not correlate significantly with each item of DVSS_SR (p > 0.05). For divergent validity, there were no significant differences in mean values of each item of DVSS_SR between genders and different levels of education (p > 0.05). Variability that can be explained for gender and educational level was below 10%. Conclusion: Translated DVSS_SR is of adequate validity and reliability for assessing DV in children. Full article

Ventriculoperitoneal shunts equipped with a reservoir and a valve to manually switch off the shunt function can be used for intraventricular injections of therapeutics in patients suffering from a communicating hydrocephalus caused by leptomeningeal metastases. These shunt devices avoid the risk of injecting therapeutics through the distal leg of the shunt system into the intraperitoneal space, which may cause toxicity. Furthermore, regular intraventricular injections of chemotherapeutics help to maintain sufficient concentrations in the ventricular space. Therefore, ventriculoperitoneal shunts equipped with an on-off valve are a useful tool to reliably inject chemotherapeutics into the ventricles. In order to systematically assess feasibility, safety, and efficacy of this procedure, we performed a retrospective analysis of all patients with leptomeningeal metastases who had received a shunt system at our institution. In total, six adult patients had a ventriculoperitoneal shunt equipped with an on-off valve implanted. Out of these six patients, two patients subsequently received intraventricular injections of chemotherapeutics. The configuration of the valve setting and the intraventricular injections were easily feasible in the setting of a neuro-oncology department. The complication of a shunt leakage occurred in one patient following the first intraventricular injection. No extra-central nervous system (CNS) toxicities were observed. In summary, ventriculoperitoneal shunts with on-off valves are useful tools for reliable intraventricular administration of therapeutics. Full article

The treatment of patients with anorexia nervosa (AN) is often challenging, due to a high degree of ambivalence towards recovery and weight gain these patients often express. One part of the multimodal treatment is the utilization of treatment contracts (i.e., contingency contracts) that aim to motivate patients to gain weight by applying positive and negative consequences for the (non-)achievement of weight goals. The main aim of this study is to assess and analyze current standards of contingency contracts’ utilization in German eating disorder centers. n = 76 mental health professionals of twelve specialized university centers in Germany that are currently or were formerly treating patients with AN in an inpatient setting participated. Most experts use contingency contracts in their clinic with weekly weight goals ranging between 500 and 700 g. Overall effectiveness and significance of contingency contracts for the inpatient treatment of patients with AN was rated high. Typical characteristics of a contingency contract in specialized German university hospital centers, such as the most frequent consequences, are described. The survey results assist the planning of further studies aiming to improve the multimodal treatment of patients with AN. For clinical practice, using external motivators such as contingency contracts as well as targeting internal motivation (e.g., by using motivational interviewing) is proposed. Full article

The purpose of this study was to evaluate the clinical characteristics of 44 pediatric patients who were diagnosed as having nutcracker syndrome (NCS). We also investigated the left renal vein Doppler ultrasonography (DUS) results, to determine whether or not there was an association between clinical symptoms and DUS findings among these patients. The clinical data from 44 pediatric patients who were diagnosed as having NCS from January 2008 to December 2015 were retrospectively reviewed. We grouped the patients according to the presenting symptoms as symptomatic (loin pain; macroscopic hematuria or both) and non-symptomatic (microscopic hematuria and proteinuria were detected incidentally) and evaluated the left renal vein DUS indices in these two groups separately. Asymptomatic NCS was found in 27 (61.4%) patients; 21 (47.7%) of whom were admitted for the evaluation of proteinuria. The most frequent presenting symptoms were left flank pain (20.5%) and macroscopic hematuria (13.6%); and 2 (4.5%) patients presented with a combination of left flank pain and macroscopic hematuria. The mean ratio of the diameter of the hilar portion of the left renal vein (LRV) to that of the aortomesenteric portion was 4.36 ± 1.55. The mean ratio of the peak velocity (PV) between the two sites of the LRV was 7.32 ± 2.68 (3.1–15.6). The differences in the ratio of the diameters were statistically significant between the two groups and significantly higher in children with asymptomatic NCS (p = 0.025). The PV ratios of the LRV (p = 0.035) were significantly higher in asymptomatic children with NCS than in the symptomatic group. Our study identifies that increased compression ratio of the LRV entrapment is most observed in orthostatic proteinuria and microscopic hematuria. Full article

Hepatocarcinogenesis comprises of multiple, complex steps that occur after liver injury and usually involve several pathways, including telomere dysfunction, cell cycle, WNT/β-catenin signaling, oxidative stress and mitochondria dysfunction, autophagy, apoptosis, and AKT/mTOR signaling. Following liver injury, gene mutations, accumulation of oxidative stress, and local inflammation lead to cell proliferation, differentiation, apoptosis, and necrosis. The persistence of this vicious cycle in turn leads to further gene mutation and dysregulation of pro- and anti-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, IL-10, IL-12, IL-13, IL-18, and transforming growth factor (TGF)-β, resulting in immune escape by means of the NF-κB and inflammasome signaling pathways. In this review, we summarize studies focusing on the roles of hepatocarcinogenesis and the immune system in liver cancer. In addition, we furnish an overview of recent basic and clinical studies to provide a strong foundation to develop novel anti-carcinogenesis targets for further treatment interventions. Full article

Background: IgA nephropathy is the most common primary glomerulonephritis in pregnancy and shares with other immunologic diseases and kidney diseases a relationship with adverse maternal outcomes, whose entity and pattern is only partially quantified. Recent studies provide new information and a systematic review regarded progression of kidney disease. The discussion of the outcomes with respect to low-risk pregnancies may help to perfect the estimation of the risks, and to identify specific research needs. Methods: A search strategy was built on Medline, EMBASE and the Cochrane review for the period January 2000–April 2017, aimed at retrieving both case series (defined as with at least 6 pregnancies in women with IgA nephropathy) and case reports, to look into rare occurrences. All papers, with or without control groups, were selected if they reported on at least one pregnancy outcome, or on long-term kidney function. Search strategy, paper selection and data extraction were done in duplicate (PROSPERO N 42016042623). Meta-analysis of case series was performed with Metanalyst Beta 3.13. Case reports were analysed narratively. Results: The search retrieved 556 papers, of which 27 were included (13 series and 14 case-reports). The case series report on 581 women with 729 pregnancies. The analysis was performed in comparison to the available control groups: 562 non-pregnant controls were available for the analysis of progression of kidney disease. As for pregnancy related outcomes (preeclampsia (PE), pregnancy induced hypertension (PIH), preterm birth, small babies), we meta-analyzed the data with respect to the only series of low-risk pregnancies (1418 pregnancies). When compared with women who never got pregnant after diagnosis of IgA nephropathy, in the present meta-analysis pregnancy in women with IgA nephropathy was not associated with a higher risk of progression of kidney disease, possibly due to the overall preserved kidney function at baseline: end-stage kidney disease (OR 0.68; CI 0.28–1.65). Conversely, the incidence of adverse pregnancy-related outcomes was increased compared to low-risk controls: PE and PIH were more than ten-fold increased (OR 11.80; CI 7.53–18.48 and OR 10.39; CI 5.45–19.80), while the increase in risk of preterm birth and “low birth weight babies” was less marked (OR 3.37; CI 1.91–5.95 and OR 2.36; CI 1.52–3.66), a discrepancy suggesting the occurrence of “late” or “maternal” PE, that may affect less severely foetal growth or shorten gestation. In conclusion, in the present meta-analysis IgA nephropathy was not associated with an increased progression of kidney disease. The more than ten-fold increased risk of PIH and PE, in combination with a doubled risk of small babies, suggests the occurrence of “late” or “maternal” PE, usually less affecting early foetal growth. This finding may be of help in defining control policies, while further research is needed to guide clinical management. Full article

Acute kidney injury (AKI) can potentially lead to the accumulation of antimicrobial drugs with significant renal clearance. Drug dosing adjustments are commonly made using the Cockcroft-Gault estimate of creatinine clearance (CLcr). The Modified Jelliffe equation is significantly better at estimating kidney function than the Cockcroft-Gault equation in the setting of AKI. The objective of this study is to assess the degree of antimicrobial dosing discordance using different glomerular filtration rate (GFR) estimating equations. This is a retrospective evaluation of antimicrobial dosing using different estimating equations for kidney function in AKI and comparison to Cockcroft-Gault estimation as a reference. Considering the Cockcroft-Gault estimate as the criterion standard, antimicrobials were appropriately adjusted at most 80.7% of the time. On average, kidney function changed by 30 mL/min over the course of an AKI episode. The median clearance at the peak serum creatinine was 27.4 (9.3–66.3) mL/min for Cockcroft Gault, 19.8 (9.8–47.0) mL/min/1.73 m² for MDRD and 20.5 (4.9–49.6) mL/min for the Modified Jelliffe equations. The discordance rate for antimicrobial dosing ranged from a minimum of 8.6% to a maximum of 16.4%. In the event of discordance, the dose administered was supra-therapeutic 100% of the time using the Modified Jelliffe equation. Use of estimating equations other than the Cockcroft Gault equation may significantly alter dosing of antimicrobials in AKI. Full article

To assess the association between intake of folate, vitamin B6, and vitamin B12 with hyperuricemia (HU) among adults from the United States (US), we extracted relevant data from 24,975 US adults aged 20–85 years from the National Health and Nutrition Examination Survey (NHANES) in 2001–2014. All dietary intake was evaluated by 24-h dietary recalls. Multivariable logistic regression analysis was performed to explore the associations after adjustment for confounders. Compared to the lowest quintile (Q1), for males, adjusted odds ratios (ORs) of HU in Q2 to Q5 of folate (dietary folate equivalent, DFE) intake were 0.84 (95% CI, 0.73–0.96), 0.84 (0.73–0.97), 0.72 (0.62–0.84), and 0.64 (0.53–0.77), respectively (p for trend <0.0001). In females, adjusted ORs in Q2 to Q4 of folate (DFE) intake were 0.84 (95% CI, 0.71–0.99), 0.81 (0.68–0.96), and 0.82 (0.68–0.99), with a p for trend of 0.1475. Our findings indicated the intakes of total folate, folic acid, food folate, folate (DFE), vitamin B12, but not vitamin B6, were inversely related to the risk of HU in males. A lower risk of HU with higher intakes of total folate, food folate, and folate (DFE) was found in females, but with no association between intakes of folic acid, vitamin B6, B12, and the risk of HU for females. Full article

There are still missing non-invasive biomarkers of chronic kidney disease (CKD) in children. Therefore, the aim of the study was to evaluate oxidative stress indicators in the non-stimulated (NWS) and stimulated saliva (SWS) of CKD children (n = 25) and healthy controls (n = 25). Salivary antioxidants (catalase (CAT), peroxidase (Px), superoxide dismutase (SOD), uric acid (UA), reduced glutathione (GSH), albumin), redox status (total antioxidant capacity (TAC), total oxidant status (TOS), oxidative stress index (OSI)), and oxidative damage products (advanced glycation end products (AGE), advanced oxidation protein products (AOPP), malondialdehyde (MDA)) were evaluated. We have demonstrated the significantly higher activity of SWS GPx and SOD, as well as elevated concentrations of UA and albumin in NWS and SWS of CKD children vs. the control group. TAC, TOS and OSI were significantly higher only in SWS, while oxidative damage products (AGE, AOPP and MDA) were significantly higher in both NWS and SWS of CKD children. ROC analysis showed a considerably high diagnostic value of AOPP in both NWS and SWS of CKD children compared to controls (AUC = 0.92; 0.98). CKD is responsible for disturbances in salivary antioxidant systems and oxidative damage to proteins and lipids. Salivary AOPP can be a potential biomarker of CKD in children. Full article

This meta-analysis aims to compare intravenous colistin monotherapy and colistin-based combination therapy against carbapenem-resistant gram-negative bacteria (GNB) infections. PubMed, Embase, and Cochrane databases were searched up to July 2018. Only randomized controlled trials (RCTs) evaluating colistin alone and colistin-based combination therapy in the treatment of carbapenem-resistant GNB infections were included. The primary outcome was all-cause mortality. Five RCTs including 791 patients were included. Overall, colistin monotherapy was associated with a risk ratio (RR) of 1.03 (95% confidence interval (CI), 0.89–1.20, I² = 0%) for all-cause mortality compared with colistin-based combination therapy. The non-significant difference was also detected in infection-related mortality (RR, 1.23, 95% CI, 0.91–1.67, I² = 0%) and microbiologic response (RR, 0.86, 95% CI, 0.72–1.04, I² = 62%). In addition, no significant difference was observed in the subgroup analysis—high or low dose, with or without a loading dose, carbapenem-resistant Acinetobacter baumannii infections, and in combination with rifampicin. Finally, colistin monotherapy was not associated with lower nephrotoxicity than colistin combination therapy (RR, 0.98; 95% CI, 0.84–1.21, I² = 0%). Based on the analysis of the five RCTs, no differences were found between colistin monotherapy and colistin-based combination therapy against carbapenem-resistant GNB infections, especially for A. baumannii infections. Full article

Disseminated peritoneal leiomyomatosis (DPL) is a rare condition that is characterized by the presence of multiple subperitoneal or peritoneal smooth muscle nodules of varying sizes on the omentum and peritoneal surfaces, grossly mimicking disseminated carcinoma. DPL usually develops in premenopausal women with a benign course, and it is often found incidentally during abdominal surgery. Malignant transformation is a rare clinical course of DPL. Only a few studies have focused on DPL transformation into a leiomyosarcoma. Herein, we describe the case of a 61-year-old woman with a history of recurrent leiomyoma of the uterus who presented with intermittent progressive abdominal pain. The imaging study revealed a huge heterogeneous density mass in the pelvic region with pulmonary and hepatic metastases. Exploratory laparotomy and debulking surgery were performed, and showed the coexistence of DPL and leiomyosarcoma. She died approximately one month after the diagnosis because of rapid progression of pleural effusion due to malignancy. This case highlights the clinical features of DPL and its malignant transformation and metastasis so physicians can make an early diagnosis and provide timely management. Full article

Randomized controlled trials (RCTs) have eligibility criteria for the inclusion of participants. Ideally, the RCT sample would be representative for the patient population that will use the drug under investigation. However, external validity may be at stake when applying too many or too restrictive eligibility criteria. The current two-part study examined (1) the currently applied eligibility criteria in Phase II and III RCTs examining sleep medication; (2) how these criteria match with the insomnia population as a whole; and (3) how inclusion rates can be changed by an adaptation of these criteria. In the first study, insomnia RCTs were screened at www.clinicaltrials.gov, and relevant eligibility criteria were identified. The second study comprised a survey among self-reported insomnia patients. It was determined to what extent RCT eligibility criteria match the characteristics of this patient population. Of the n = 519 patients that completed the survey only n = 2 (0.4%) met all eligibility criteria of current RCTs. RCT enrolment criteria are not representative for the insomnia patient population as a whole. Being less rigorous in applying upper or lower criteria limits results in a significant increase in the number of eligible patients, and increases the representativeness of RCTs for the insomnia patient population as a whole. The current analysis demonstrates that is important to thoroughly reconsider the use eligibility criteria and their inclusion ranges, and to have a theoretical basis for using them. Full article

This study aims to investigate the association between oxygenation saturation index (OSI) and the outcome of acute respiratory distress syndrome (ARDS) patients, and assess the predictive performance of OSI for ARDS patients’ mortality. This study was conducted at one regional hospital with 66 adult intensive care unit (ICU) beds. All patients with ARDS were identified between November 1 2016 and May 31 2018, and their clinical information was retrospectively collected. The lowest PaO₂/FiO₂ ratio and SpO₂/FiO₂ ratio and highest mean airway pressure (MAP) were recorded on the first day of ARDS; and oxygen index (OI) and OSI were calculated as (FiO₂ × MAP × 100)/PaO₂, and (FiO₂ × MAP × 100) /SpO₂ accordingly. During the study period, a total of 101 patients with ARDS were enrolled, and their mean age was 69.2 years. The overall in-ICU and in-hospital mortality rate was 57.4% and 61.4%, respectively. The patients with in-ICU mortality had higher APACHE II score than the survivors (31.6 ± 9.8 vs. 23.0 ± 9.1, p < 0.001). In addition, mortalities had lower SpO₂, and SpO₂/FiO₂ ratios than the survivors (both p < 0.05). In contrast, survivors had lower OI, and OSI than the mortalities (both p = 0.008). Both OSI (area under curve (AUC) = 0.656, p = 0.008) and OI (AUC = 0.654, p = 0.008) had good predictive performance of mortality among ARDS patients using receiver-operating characteristics (ROC) curves analysis. In addition, the AUC of SpO₂/FiO₂ (AUC = 0.616, p = 0.046) had better performance for mortality prediction than PaO₂/FiO₂ (AUC = 0.603, p = 0.08). The patients with OSI greater than 12 had a higher risk of mortality than OSI < 12 (adjusted OR, 5.22, 95% CI, 1.31–20.76, p = 0.019). In contrast, OI, PaO₂/FiO₂, and SpO₂/FiO₂ were not found to be significantly associated with increased mortality. OSI is significantly associated with the increased mortality of ARDS patients and can also be a good outcome predictor. Full article

Background: The neutrophil–lymphocyte ratio (NLR) is a valuable prognostic or predictive biomarker in various diseases, but the genetic factors that underlie the NLR have not been studied. We attempted to investigate polymorphisms related to NLR phenotype and analyze their ability to predict metabolic risks. Methods: A genome-wide association study was performed with log-transformed NLR using an Affymetrix Axiom™ KORV1.1-96 Array. Regression models for metabolic risk status were designed using the identified significant single-nucleotide polymorphisms (SNPs). Results: We identified four SNPs near the TMEM116, NAA25, and PTPN11 genes that were associated with the NLR. The top SNP associated with the log-transformed NLR was rs76181728 in TMEM116. A case–control study was performed to analyze the metabolic risks associated with each SNP after adjusting for age, sex, and body mass index (BMI). Three SNPs displayed significant odds ratios (ORs) for increased blood pressure and increased waist circumference. In the regression model for metabolic syndrome, rs76181728 showed a significant association (OR = 1.465, 95% confidence interval (CI) = 1.091–1.969, P = 0.011) after adjustment for the NLR phenotype. Conclusions: We identified four novel SNPs that are associated with the NLR in healthy Koreans. SNPs in relevant genes might therefore serve as biomarkers for metabolic risks. Full article

Background: While obesity is a chronic condition that predisposes patients to other more serious disorders, the prevalence and the documentation of obesity as diagnosis has not been extensively studied in hospitalized patients. We conducted a retrospective chart review to investigate the prevalence and documentation of obesity as a diagnosis among patients admitted to our medical center. Method: IRB approval was obtained for this retrospective study. Body mass index (BMI) as per CDC, admission and discharge diagnosis of obesity and common comorbidities (hypertension, diabetes, hyperlipidemia, coronary artery disease, congestive heart disease, chronic kidney disease and chronic obstructive pulmonary disease) were recorded. The length of stay in the hospital was also calculated. We also investigated whether counselling was provided to the obese patients for weight loss. Results: A total of 540 consecutive patients were reviewed with a mean age was 66 ± 6 years. Out of 540 patients only 182 (34%) had normal weight, 188 (35%) of the patients were overweight and 170 (31%) patients were obese. Of the obese group, 55% were female and 45% were male.100 (59%) had class I obesity, 43 (25%) had class II obesity and 27 (16%) class III obesity. Of the obese patients 40/170 (23.5%) patients had obesity documented on the admission problem list and only 21 (12%) had obesity documented as a discharge diagnosis. Only 3 (2%) patients were given appropriate counseling and referral for obesity management during the hospitalization. Comorbidities and their prevalence included, hypertension (68%), diabetes mellitus (35%), hyperlipidemia (36%), coronary artery disease (18%), chronic kidney disease (17%), congestive heart failure (18%) and COPD (24%). The average length of stay in normal weight, overweight and obese patients was similar for all three groups (4.5 ± 0.5 days). Conclusion: A significant number of hospitalized patients were overweight and obese. An overwhelming percentage never had weight status documented. Hospitalization offers health care providers a window of opportunity to identify obesity, communicate risks, and initiate weight management interventions. Full article

The ideal circumstances for whether and when to start RRT remain unclear. The outcome predictive ability of acute kidney injury (AKI) biomarkers measuring at dialysis initializing need more validation. This prospective, multi-center observational cohort study enrolled 257 patients with AKI undergoing renal replacement therapy (RRT) shortly after admission. At the start of RRT, blood and urine samples were collected for relevant biomarker measurement. RRT dependence and all-cause mortality were recorded up to 90 days after discharge. Areas under the receiver operator characteristic (AUROC) curves and a multivariate generalized additive model were applied to predict outcomes. One hundred and thirty-five (52.5%) patients died within 90 days of hospital discharge. Plasma c-terminal FGF-23 (cFGF-23) had the best discriminative ability (AUROC, 0.687) as compared with intact FGF-23 (iFGF-23) (AUROC, 0.504), creatinine-adjusted urine neutrophil gelatinase-associated lipocalin (AUROC, 0.599), and adjusted urine cFGF-23 (AUROC, 0.653) regardless whether patients were alive or not on day 90. Plasma cFGF-23 levels above 2050 RU/mL were independently associated with higher 90-day mortality (HR 1.76, p = 0.020). Higher cFGF-23 levels predicted less weaning from dialysis in survivors (HR, 0.62, p = 0.032), taking mortality as a competing risk. Adding cFGF-23 measurement to the AKI risk predicting score significantly improved risk stratification and 90-day mortality prediction (total net reclassification improvement = 0.148; p = 0.002). In patients with AKI who required RRT, increased plasma cFGF-23 levels correlated with higher 90-day overall mortality after discharge and predicted worse kidney recovery in survivors. When coupled to the AKI risk predicting score, cFGF-23 significantly improved mortality risk prediction. This observation adds evidence that cFGF-23 could be used as an optimal timing biomarker to initiate RRT. Full article

Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease characterised by chronic, progressive scarring of the lungs and the pathological hallmark of usual interstitial pneumonia. Current paradigms suggest alveolar epithelial cell damage is a key initiating factor. Globally, incidence of the disease is rising, with associated high morbidity, mortality, and economic healthcare burden. Diagnosis relies on a multidisciplinary team approach with exclusion of other causes of interstitial lung disease. Over recent years, two novel antifibrotic therapies, pirfenidone and nintedanib, have been developed, providing treatment options for many patients with IPF, with several other agents in early clinical trials. Current efforts are directed at identifying key biomarkers that may direct more customized patient-centred healthcare to improve outcomes for these patients in the future. Full article

The relationship between psychosocial stress at work and mental health outcome is well-known. Brain-imaging studies hypothesize morphological brain modifications connected to work-related stress. To our knowledge this is the first study describing the link between work characteristics and brain imaging in a sample of work-related psychiatric patients assessed according to standardized clinical and diagnostic criteria. The aims of the study are: (1) to evaluate hippocampal and whole brain volumes in work-related psychiatric disturbances; (2) to verify the relationship between brain changes and the anxious and/or depressive symptoms; (3) to observe the relationship between the brain changes and the degree of the bullying at workplace. The hippocampus and whole brain volumes of 23 patients with work-related adjustment-disorders were compared with 15 controls by means of MRI. MR images highlight a smaller hippocampal volume in patients compared with controls. Significant reduction in the patients’ gray matter was found in three brain areas: right inferior temporal gyrus, left cuneus, left inferior occipital gyrus. The reduction of the hippocampi volumes was related to work distress and, above all, to bullying at workplace. The results confirm that the morphological brain abnormalities could be involved in work-related psychiatric disturbances. Full article

Nephrology is a complex discipline, including care of kidney disease, dialysis, and transplantation. While in Europe, about 1:10 individuals is affected by chronic kidney disease (CKD), 1:1000 lives thanks to dialysis or transplantation, whose costs are as high as 2% of all the health care budget. Nephrology has important links with surgery, bioethics, cardiovascular and internal medicine, and is, not surprisingly, in a delicate balance between specialization and comprehensiveness, development and consolidation, cost constraints, and competition with internal medicine and other specialties. This paper proposes an interpretation of the different systems of nephrology care summarising the present choices into three not mutually exclusive main models (“scientific”, “pragmatic”, “holistic”, or “comprehensive”), and hypothesizing an “ideal-utopic” prevention-based fourth one. The so-called scientific model is built around kidney transplantation and care of glomerulonephritis and immunologic diseases, which probably pose the most important challenges in our discipline, but do not mirror the most common clinical problems. Conversely, the pragmatic one is built around dialysis (the most expensive and frequent mode of renal replacement therapy) and pre-dialysis treatment, focusing attention on the most common diseases, the holistic, or comprehensive, model comprehends both, and is integrated by several subspecialties, such as interventional nephrology, obstetric nephrology, and the ideal-utopic one is based upon prevention, and early care of common diseases. Each model has strength and weakness, which are commented to enhance discussion on the crucial issue of the philosophy of care behind its practical organization. Increased reflection and research on models of nephrology care is urgently needed if we wish to rise to the challenge of providing earlier and better care for older and more complex kidney patients with acute and chronic kidney diseases, with reduced budgets. Full article

High physical activity or workload has been associated with intervertebral disc degeneration. However, there is little data on physicians’ risks of disc disease. The study aimed to investigate the incidences of spinal problems among neurologists and neurosurgeons. A cohort of neurologists and neurosurgeons was derived from Taiwan’s national research database. During the study period, the incidences of intervertebral disc herniation or spondylosis among these specialists were calculated. Another one-to-one by propensity score matched cohort, composed of neurologists and neurosurgeons, was also analyzed. A Cox regression hazard ratio (HR) model and Kaplan-Meier analysis were conducted to compare the risks and incidences. The entire cohort comprised 481 and 317 newly board-certified neurologists and neurosurgeons, respectively. During the 15 years of follow-up, neurosurgeons were approximately six-fold more likely to develop disc problems than neurologists (crude HR = 5.98 and adjusted HR = 6.08, both p < 0.05). In the one-to-one propensity-score matched cohort (317 neurologists versus 317 neurosurgeons), there were even higher risks among neurosurgeons than neurologists (crude HR = 8.15, and adjusted HR = 10.14, both p < 0.05). Neurosurgeons have a higher chance of intervertebral disc disorders than neurologists. This is potentially an occupational risk that warrants further investigation. Full article

Pancreatic cancer is the fourth leading cause of cancer death. Soluble receptor for glycation end products (sRAGE), which is modulated by anti-hypertensive (HT) medications, has been inversely associated with pancreatic cancer. However, the association between commonly used anti-HT medications and risk of pancreatic cancer is unknown. A total of 145,551 postmenopausal women from the Women Health Initiative (WHI) Study were included in analysis. Use of angiotensin converting enzyme inhibitors (ACEi), β-blockers, calcium channel blockers (CCBs) and diuretics was ascertained at baseline (1993–1998). Baseline sRAGE levels were measured among a subset of 2104 participants using an immunoassay. Multivariable Cox proportional hazard regression model was performed to estimate hazard ratios (HRs) and its 95% confidence intervals (CIs) for pancreatic cancer in association with anti-HT medications. Increased risk of pancreatic cancer was found among users of short-acting CCB (HR = 1.66, 95% CI: 1.20–2.28) and long-term (≥3 years) users of short-acting CCB (HR = 2.07, 95% CI: 1.42–3.02) compared to users of other anti-HT medications. Average sRAGE levels were lower in short-acting CCB users than users of other anti-HT medications (1173 versus 1454 pg/mL, p = 0.038). Non-statistically significant reduced risk of pancreatic cancer was found among users of β-blockers (HR = 0.80, 95% CI: 0.60–1.07). Average sRAGE levels were higher in β-blockers users than users of other anti-HT medications (1692 versus 1454 pg/mL, p > 0.05). Future studies are warranted to confirm these findings and elucidate potential mechanisms by which anti-HT medications influence development of pancreatic cancer. Full article