Folate treatment of pregnant rat dams abolishes metabolic effects in female offspring induced by a paternal pre-conception unhealthy diet

Aims/hypothesis

Paternal high-fat diet prior to mating programmes impaired glucose tolerance in female offspring. We examined whether the metabolic consequences in offspring could be abolished by folate treatment of either the male rats before mating or the corresponding female rats during pregnancy.

Methods

Male F0 rats were fed either control diet or high-fat, high-sucrose and high-salt diet (HFSSD), with or without folate, before mating. Male rats were mated with control-diet-fed dams. After mating, the F0 dams were fed control diet with or without folate during pregnancy.

Results

Male, but not female offspring of HFSSD-fed founders were heavier than those of control-diet-fed counterparts (p?<?0.05 and p?=?0.066 in males and females, respectively). Both male and female offspring of HFSSD-fed founders were longer compared with control (p?<?0.01 for both sexes). Folate treatment of the pregnant dams abolished the effect of the paternal diet on the offspring’s body length (p ? 0.05). Female offspring of HFSSD-fed founders developed impaired glucose tolerance, which was restored by folate treatment of the dams during pregnancy. The beta cell density per pancreatic islet was decreased in offspring of HFSSD-fed rats (?20% in male and ?15% in female F1 offspring, p ? 0.001 vs controls). Folate treatment significantly increased the beta cell density (4.3% and 3.3% after folate supplementation given to dams and founders, respectively, p ? 0.05 vs the offspring of HFSSD-fed male rats). Changes in liver connective tissue of female offspring of HFSSD-fed founders were ameliorated by treatment of dams with folate (p ? 0.01). Hepatic Ppara gene expression was upregulated in female offspring only (1.51-fold, p ? 0.05) and was restored in the female offspring by folate treatment (p ? 0.05). We observed an increase in hepatic Lcn2 and Tmcc2 expression in female offspring born to male rats exposed to an unhealthy diet during spermatogenesis before mating (p ? 0.05 vs controls). Folate treatment of the corresponding dams during pregnancy abolished this effect (p ? 0.05). Analysis of DNA methylation levels of CpG islands in the Ppara, Lcn2 and Tmcc2 promoter regions revealed that the paternal unhealthy diet induced alterations in the methylation pattern. These patterns were also affected by folate treatment. Total liver DNA methylation was increased by 1.52-fold in female offspring born to male rats on an unhealthy diet prior to mating (p ? 0.05). This effect was abolished by folate treatment during pregnancy (p ? 0.05 vs the offspring of HFSSD-fed male rats).

Conclusions/interpretation

Folate treatment of pregnant dams restores effects on female offspring’s glucose metabolism induced by pre-conception male founder HFSSD.

     

Gender Differences in Platelet Reactivity in Patients Receiving Dual Antiplatelet Therapy

Background

Cardiovascular risk is still underestimated in women, experiencing higher mortality and worse prognosis after acute cardiovascular events. Gender differences have been reported in thrombotic and hemorrhagic risk during dual antiplatelet therapy (DAPT), thus suggesting a potential variability in platelet reactivity according to sex. The aim of the present study was to assess the role of gender on platelet function and the prevalence of high-on treatment residual platelet reactivity (HRPR) during DAPT in patients with recent acute coronary syndrome or percutaneous coronary revascularization.

Methods

Patients treated with DAPT (ASA and clopidogrel or ticagrelor) were scheduled for platelet function assessment at 30–90 days post-discharge. By whole blood impedance aggregometry, HRPR was considered for ASPI test >862 AU*min (for ASA) and ADP test values ≥417 AU*min (for ADP-antagonists).

Results

We included 541 patients on DAPT, 122 (22.6 %) of whom were females. Females were older (p < 0.001), displayed more frequently hypercholesterolemia (p = 0.003), renal failure (p = 0.04), acute presentation (p < 0.001), higher cholesterol levels and platelets count (p < 0.001). Inverse association was demonstrated with smoking (p < 0.001), previous PCI (p = 0.04) and statin use (p = 0.03), creatinine and haemoglobin (p < 0.001). Female gender did not influence mean platelet reactivity or the prevalence of HRPR for ASA (1.7 % vs 1.4 %, OR[95%CI] = 1.14[0.17–4.36], p = 0.99, adjusted OR[95%CI] = 1.54[0.20–11.6], p = 0.68) or ADP-antagonists (26.3 % vs 22.8 %, OR[95%CI] = 1.17[0.52–1.34], p = 0.45, adjusted OR[95%CI] = 1.05[0.59–1.86], p = 0.87). Results did not change when considering separately the 309 patients treated with clopidogrel (34 % vs 31.3 %, OR[95%CI] = 1.13[0.62–2.07], p = 0.76, adjusted OR[95%CI] = 1.35[0.63–2.9], p = 0.44 for females vs males), or patients (n = 232) on ticagrelor (20.4 % vs 11.1 %, OR[95%CI] = 2.27[0.99–5.17], p = 0.06 for females vs males), confirmed after correction for baseline differences (adjusted OR[95%CI] = 1.21[0.28–2.29], p = 0.68).

Conclusion

In patients receiving dual antiplatelet therapy, gender does not impact on the prevalence of high-on treatment residual platelet reactivity (HRPR) with the major antiplatelet agents ASA, clopidogrel or ticagrelor.

     

Temporal trajectory of quality of life and its predictors in recipients of hematopoietic stem cell transplantation

This prospective longitudinal study evaluated the temporal trajectory of health-related quality of life (HRQOL) and its associated factors in patients who received hematopoietic stem cell transplantation (SCT) 6 months after transplantation. Eighty-nine adult patients who were admitted to Seoul National University Hospital for SCT were consecutively included in the study. The participants completed three standardized questionnaires: Insomnia Severity Index, Hospital Anxiety and Depression Scale, and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire. The participants completed the study questionnaires at three time points: before SCT (T1), immediately after SCT (T1), and 6 months after SCT (T3). Immediately after SCT, HRQOL decreased significantly (p?<?0.001), followed by recovery over 6 months. The conditioning regimen for SCT showed no correlation with HRQOL at T2 (p?=?0.283) or T3 (p?=?0.799), with no significant difference in HRQOL between allogeneic and autologous SCT recipients at T2 (p?=?0.829) or T3 (p?=?0.824). Depression (p?=?0.042), pain (p?=?0.023), and appetite loss (p?=?0.004) negatively influenced HRQOL at T1, whereas only pain (p?=?0.048) remained an important factor at T2. Six months after SCT, the two most frequent symptoms, fatigue and financial problems, became major factors (p?=?0.004 and p?=?0.005, respectively). Depression began to play an important role in HRQOL again at T3 (p?=?0.040). These findings demonstrate that SCT recipients need both psychological and medical support to achieve a better HRQOL after SCT.     

The Value of the Electrocardiogram for Evaluating Prognosis in Patients with Idiopathic Pulmonary Arterial Hypertension

Background

Association between electrocardiography (ECG) features and right ventricular anatomy and physiology has been established. This study is aimed to identify the value of 12-lead ECG in evaluating prognosis of patients with idiopathic pulmonary arterial hypertension (IPAH).

Method

194 patients with newly diagnosed IPAH were included in this study. Correlations between electrocardiography variables and hemodynamics were assessed. Univariate and multivariable cox regression analysis were performed to identify ECG variables for predicting all-cause mortality in IPAH.

Results

Partial correlation analysis showed that P wave amplitude in lead II correlated with the mean pulmonary arterial pressure (mPAP, r = 0.349, p ≤ 0.001) and cardiac index (CI, r = ?0.224, p = 0.002); R wave amplitude in V1 correlated with mPAP (r = 0.359, p ≤ 0.001); S wave amplitude in V6 correlated with mPAP (r = 0.259, p = 0.030) and CI (r = ?0.220, p = 0.003). P wave amplitude in lead II (HR 1.555, p = 0.033) and R wave amplitude in lead aVR (HR 5.058, p < 0.001) were the independent predictors of all-cause mortality. Kaplan–Meier survival curves showed patients with a p ≥ 0.25 mv in lead II, and R ≥ 0.4 mv in lead aVR had lower 3-year survival (55 vs. 91%, p < 0.001).

Conclusion

Specific lead-12 ECG features could reflect right ventricular overload hemodynamics, and are useful to evaluate prognosis of patients with IPAH.

     

Can a collaborative subspecialty antimicrobial stewardship intervention have lasting effects?

Objective

We previously demonstrated the benefit of direct, daily collaboration between infectious disease (ID) and critical care practitioners (CCP) on guideline adherence and antibiotic use in the medical intensive care unit (MICU). In this post-intervention review, we sought to establish whether the effect on antibiotic use and guideline adherence was sustainable.

Design

A retrospective review of 87 patients, admitted to the 24-bed MICU, was done 3 (n = 45) and 6 months (n = 42) after the intervention.

Measurements

Data included demographics, severity indicators, admitting pathology, infectious diagnosis, clinical outcomes [mechanical ventilation days (MVD) and MICU length of stay (LOS), antibiotic days of therapy (DOT), in-hospital mortality], and antibiotic appropriateness based on current guidelines.

Results

In the 3-month (3-PI) and 6-month post-intervention (6-PI), there were no significant differences in the APACHE II score, MVD, LOS, DOT, or total antibiotic use at 3 (p = 0.59) and 6-PI (p = 0.87). There was no change in the mean use of extended-spectrum penicillins, cephalosporin, and carbapenems. While there were significant differences in vancomycin usage at 3-PI [3.1 DOT vs. 4.3 DOT (p = 0.007)], this finding was not seen after 6 months [3.1 DOT vs. 3.4 DOT (p = 0.08)]. When compared to the intervention period, the inappropriateness of antibiotic use at 3 (p = 1.00) and 6-PI (p = 0.30) did not change significantly.

Conclusions

There were no significant differences in either total antibiotic use or inappropriate antibiotic use at the 6-PI time period. Continuous, daily, direct collaboration between ID and CCP, once implemented, can have lasting effects even at 6 months after the interaction has been discontinued.

     

Diagnostic utility of zinc protoporphyrin to detect iron deficiency in Kenyan preschool children: a community-based survey

Background

Zinc protoporphyrin (ZPP) has been used to screen and manage iron deficiency in individual children, but it has also been recommended to assess population iron status. The diagnostic utility of ZPP used in combination with haemoglobin concentration has not been evaluated in pre-school children. We aimed to a) identify factors associated with ZPP in children aged 12–36 months; b) assess the diagnostic performance and utility of ZPP, either alone or in combination with haemoglobin, to detect iron deficiency.

Methods

We used baseline data from 338 Kenyan children enrolled in a community-based randomised trial. To identify factors related to ZZP measured in whole blood or erythrocytes, we used bivariate and multiple linear regression analysis. To assess diagnostic performance, we excluded children with elevated plasma concentrations of C-reactive protein or α ₁-acid glycoprotein, and with Plasmodium infection, and we analysed receiver operating characteristics (ROC) curves, with iron deficiency defined as plasma ferritin concentration < 12 μg/L. We also developed models to assess the diagnostic utility of ZPP and haemoglobin concentration when used to screen for iron deficiency.

Results

Whole blood ZPP and erythrocyte ZPP were independently associated with haemoglobin concentration, Plasmodium infection and plasma concentrations of soluble transferrin receptor, ferritin, and C-reactive protein. In children without inflammation or Plasmodium infection, the prevalence of true iron deficiency was 32.1%, compared to prevalence of 97.5% and 95.1% when assessed by whole blood ZPP and erythrocyte ZPP with conventional cut-off points (70 μmol/mol and 40 μmol/mol haem, respectively). Addition of whole blood ZPP or erythrocyte ZPP to haemoglobin concentration increased the area-under-the-ROC-curve (84.0%, p = 0.003, and 84.2%, p = 0.001, respectively, versus 62.7%). A diagnostic rule (0.038689 [haemoglobin concentration, g/L] + 0.00694 [whole blood ZPP, μmol/mol haem] >5.93120) correctly ruled out iron deficiency in 37.4%–53.7% of children screened, depending on the true prevalence, with both specificity and negative predictive value ≥90%.

Conclusions

In young children, whole blood ZPP and erythrocyte ZPP have added diagnostic value in detecting iron deficiency compared to haemoglobin concentration alone. A single diagnostic score based on haemoglobin concentration and whole blood ZPP can rule out iron deficiency in a substantial proportion of children screened.

Trial registration

ClinicalTrials.gov NCT02073149 (25 February 2014).

     

Early Trends in Bronchoscopic Lung Volume Reduction: A Systematic Review and Meta-analysis of Efficacy Parameters

Introduction

The goal of our systematic review and meta-analysis is to examine the therapeutic effectiveness of bronchoscopic lung volume reduction (BLVR), and to compare it with medical management and lung volume reduction surgery.

Methods

Variables of interest were absolute change in FEV1, 6MWT, and SGRQ. Meta-analysis was performed for the BLVR modalities with ≥3 trials. Of the 18 shortlisted publications, only valves (four trials; n = 159) and coils (six trials; n = 194) qualified for meta-analysis. To avoid redundant reporting for valves, only the data for intact fissure subjects were analyzed. Outcome data are presented as the mean difference from baseline with 95% confidence interval at 6-months follow-up.

Results

For BLVR using valves, the pooled mean difference (PMD) for FEV1 was 0.146 L (95% CI 0.111–0.181; p < 0.001), 6MWT was 45.225 meters (95% CI 26.954–63.495; p < 0.001), and SGRQ was ?8.825 points (95% CI ?14.824 to ?2.825; p = 0.004). All the PMDs were statistically significant and higher than their respective minimal clinically important difference (MCID). For BLVR using coils, the PMD for FEV1 was 0.080 L (95% CI 0.057–0.104; p < 0.001), 6MWT was 45.320 meters (95% CI 28.040–62.600; p < 0.001), and SGRQ was ?10.570 points (95% CI ?13.299 to ?7.841; p < 0.001). All three variables showed statistically significant PMDs but that for FEV1 was smaller than the MCID. Data from BLVR modalities with <3 major publications are reviewed in the discussion section.

Conclusions

BLVR offers early promise in the palliation of advanced emphysema. Better characterization of patients to identify phenotypes that will derive sustained benefit is needed.

     

Impact of perioperative hypoglycaemia in subjects with diabetes undergoing colorectal surgery

Introduction

This study explores the association between perioperative hypoglycaemia and surgical outcomes in subjects with diabetes, undergoing colorectal surgery.

Methods

A retrospective review of 149 subjects with Type 2 Diabetes Mellitus (DM) who underwent colorectal surgery between 2010 and 2015 was performed. Perioperative glucose levels, glycated haemoglobin (HbA1c) measurements within 3 months of surgery and surgical complications based on Clavien-Dindo classification were analysed.

Results

The mean age was 67 years (67 ± 11.2). Perioperative hypoglycaemia was found in 7.4% of subjects. The mean HbA1c of subjects with Clavien 2 and above surgical complications were higher than patients with Clavien 1 or no complications, Hba1c 7.6% (7.6 ± 2.5%) and 7.0% (7.0 ± 1.1%, p = 0.008), respectively. Similar findings in subjects with Clavien 3 and above complications, HbA1c of 8.2% (8.2 ± 3.9%) as compared to those with Clavien 2 and below complications, 7.2% (7.2 ± 1.5%, p = 0.001). Adjusted multivariate analysis showed that hypoglycaemia was significantly associated with Clavien 2 and above surgical complications, OR of 19.0 (CI 2.23–162, p = 0.007). Preoperative hypoglycaemia was associated with Clavien 2 and above surgical complications, OR 10.7 (CI 1.22–94.1, p = 0.032). Suboptimal glycaemic control (Hba1c >8.0%) was significantly associated with Clavien 2 and above complications, OR 2.48 (CI 1.04–5.91, p = 0.04), but not with Clavien 3 and above complications, OR 1.50 (CI 0.450–4.98, p = 0.511).

Conclusion

Perioperative hypoglycaemia is associated with adverse surgical outcomes in diabetic patients undergoing colorectal surgery. Prevention of hypoglycaemia may improve surgical outcomes. HbA1c is an independent predictor for adverse surgical outcomes.

     

Damage control surgery in perforated diverticulitis: ongoing peritonitis at second surgery predicts a worse outcome

Purpose

Damage control strategy (DCS) is a two-staged procedure for the treatment of perforated diverticular disease complicated by generalized peritonitis. The aim of this retrospective multicenter cohort study was to evaluate the prognostic impact of an ongoing peritonitis at the time of second surgery.

Methods

Consecutive patients who underwent DCS for perforated diverticular disease of the sigmoid colon with generalized peritonitis at four surgical centers were included. Damage control strategy is a two-stage emergency procedure: limited resection of the diseased colonic segment, closure of oral and aboral colon, and application of a negative pressure assisted abdominal closure system at the initial surgery followed by second laparotomy 48 h later. Therein, decision for definite reconstruction (anastomosis or Hartmann’s procedure (HP)) is made. An ongoing peritonitis at second surgery was defined as presence of visible fibrinous, purulent, or fecal peritoneal fluid. Microbiologic findings from peritoneal smear at first surgery were collected and analyzed.

Results

Between 5/2011 and 7/2017, 74 patients underwent a DCS for perforated diverticular disease complicated by generalized peritonitis (female: 40, male: 34). At second surgery, 55% presented with ongoing peritonitis (OP). Patients with OP had higher rate of organ failure (32 vs. 9%, p =?0.024), higher Mannheim Peritonitis Index (25.2 vs. 18.9; p =?0.001), and increased operation time (105 vs. 84 min., p =?0.008) at first surgery. An anastomosis was constructed in all patients with no OP (nOP) at second surgery as opposed to 71% in the OP group (p <?0.001). Complication rate (44 vs. 24%, p =?0.092), mortality (12 vs. 0%, p =?0.061), overall number of surgeries (3.4 vs. 2.4, p =?0.017), enterostomy rate (76 vs. 36%, p =?0.001), and length of hospital stay (25 vs. 18.8 days, p =?0.03) were all increased in OP group. OP at second surgery occurred significantly more often in patients with Enterococcus infection (81 vs. 44%, p =?0.005) and with fungal infection (100 vs. 49%, p =?0.007). In a multivariate analysis, Enterococcus infection was associated with increased morbidity (67 vs. 21%, p <?0.001), enterostomy rate (81 vs. 48%, p =?0.017), and anastomotic leakage (29 vs. 6%, p =?0.042), whereas fungal peritonitis was associated with an increased mortality (43 vs. 4%, p =?0.014).

Conclusion

Ongoing peritonitis after DCS is a predictor of a worse outcome in patients with perforated diverticulitis. Enterococcal and fungal infections have a negative impact on occurrence of OP and overall outcome.

     

Circulating Bone Marrow-Derived CD45−/CD34+/CD133+/VEGF+ Endothelial Progenitor Cells in Adults with Crohn’s Disease

Background

Circulating endothelial progenitor cells (EPCs) are bone marrow-derived stem cells able to migrate to sites of damaged endothelium and differentiate into endothelial cells. Altered EPC level and function have been described in various inflammatory diseases and have been shown to augment vasculogenesis in murine models. Previous studies of EPC in the context of Crohn’s disease (CD) have yielded conflicting results.

Aim

To determine whether the circulating levels of EPCs are changed in the context of CD.

Methods

CD patients and healthy controls were recruited. Disease activity was assessed by CDAI. Peripheral blood mononuclear cells were isolated and EPC numbers evaluated by FACS analysis using anti-CD34, anti-VEGF receptor-2, anti-CD133, and anti-CD45 markers.

Results

Eighty-three subjects, including 32 CD patients and 51 controls were recruited, including 19 (59.4 %) and 23 (45 %) males (p = 0.26), aged 34.8 ± 14.9 and 43.3 ± 18.5 years (p = 0.64), in cases and controls, respectively. Mean CDAI was 147 ± 97, disease duration was 12.7 ± 11.1 years, and 28 (87.5 %) were receiving biologics for a mean duration of 21.7 ± 16.8 months. The mean level of peripheral EPCs in CD patients was 0.050 ± 0.086 percent and 0.007 ± 0.013 % in controls (p < 0.01). There was no significant correlation between EPC levels and age (r = ?0.13, p = 0.47), CDAI (r = ?0.26, p = 0.15), disease duration (r = ?0.04, p = 0.84), or duration of treatment with biologics (r = 0.004, p = 0.99).

Conclusion

EPCs are elevated in patients with CD. Further studies are needed to examine the function of EPCs and their possible role as a marker of disease severity or therapeutic response.

     

What is the best tool for transanal endoscopic microsurgery (TEM)? A case-matched study in 74 patients comparing a standard platform and a disposable material

Purpose

Transanal endoscopic microsurgery (TEM) is the gold standard for local excision of rectal lesions, but no study exists concerning the best material. The objective was to compare TEM using a disposable material vs a standard platform through a case-matched study.

Methods

Patients who underwent TEM for rectal neoplasms were identified from prospective databases in two tertiary referral centers and matched according to four criteria (sex, tumor location, size, distance from the anal verge): TEM using a disposable material (GelPoint Applied®; group A) and TEM using a standard TEO® platform (Karl Storz, Tuttlingen, Germany; group B).

Results

A total of 74 patients were included and divided into group A (n = 33) and group B (n = 41). Full-thickness resection was less frequent in group A (85%) than B (100%; p = 0.01). Adenocarcinoma was less frequent in group A than B: 27 vs 42% (p = 0.03). No difference was noted regarding median operative time (53 vs 53 min; p = 0.6) and a peritoneal perforation rate (6 vs 20%; p = 0.17). Median length of stay was shorter in group A than B (4 vs 5 days; p < 0.008). No significant difference was noted for major morbidity (12 vs 10%; p = 0.66), R1 resection (21 vs 10%; p = 0.2), and recurrence rates (8 vs 7%; p = 0.62). No difference was noted for rectal stenosis (3 vs 12%; p = 0.22) and transit disorder rates (12 vs 17%; p = 0.74).

Conclusions

Our study suggested that TEM can be performed using either a TEO® platform or a disposable material, with similar surgical results. The TEO® platform seems to be superior to obtain full-thickness and R0 resection.

     

Risk for latent and active tuberculosis in Germany

Purpose

Few individuals that are latently infected with M. tuberculosis latent tuberculosis infection(LTBI) progress to active disease. We investigated risk factors for LTBI and active pulmonary tuberculosis (PTB) in Germany.

Methods

Healthy household contacts (HHCs), health care workers (HCWs) exposed to M. tuberculosis and PTB patients were recruited at 18 German centres. Interferon-γ release assay (IGRA) testing was performed. LTBI risk factors were evaluated by comparing IGRA-positive with IGRA-negative contacts. Risk factors for tuberculosis were evaluated by comparing PTB patients with HHCs.

Results

From 2008–2014, 603 HHCs, 295 HCWs and 856 PTBs were recruited. LTBI was found in 34.5% of HHCs and in 38.9% of HCWs. In HCWs, care for coughing patients (p = 0.02) and longstanding nursing occupation (p = 0.04) were associated with LTBI. In HHCs, predictors for LTBI were a diseased partner (odds ratio 4.39), sexual contact to a diseased partner and substance dependency (all p < 0.001). PTB was associated with male sex, low body weight (p < 0.0001), alcoholism (15.0 vs 5.9%; p < 0.0001), glucocorticoid therapy (7.2 vs 2.0%; p = 0.004) and diabetes (7.8 vs. 4.0%; p = 0.04). No contact developed active tuberculosis within 2 years follow-up.

Conclusions

Positive IGRA responses are frequent among exposed HHCs and HCWs in Germany and are poor predictors for the development of active tuberculosis.

     

Prognostic influence of hepatic margin after resection of colorectal liver metastasis: role of modern preoperative chemotherapy

Purpose

Modern chemotherapy (CTX) increases survival in stage IV colorectal cancer. In colorectal liver metastases (CLM), neoadjuvant (neo) CTX may increase resectability and improve survival. Due to widespread use of CTX in CLM, recent studies assessed the role of the hepatic margin after CTX, with conflicting results. We evaluated the outcome after resection of CLM in relation to CTX and hepatic resection status.

Methods

Since 2000, 334 patients with first hepatic resection for isolated CLM were analyzed. Thirty-two percent had neoadjuvant chemotherapy (targeted therapy in 42%). Sixty-eight percent never had CTX before hepatectomy or longer than 6 months before resection. The results were gained by analysis of our prospective database.

Results

Positive hepatic margins occurred in 8% (independent of neoCTx). Patients after neoCTX had higher numbers of CLM (p < 0.01) and a longer duration of surgery (p < 0.03). After hepatectomy, 5-year survival was 45% and correlated strongly with the margin status (47% in R-0 and 21% in R-1; p < 0.001). Survival also correlated with margin status in the subgroups with neoCTX (p < 0.01) or without neoCTx (p < 0.01). In multivariate analysis of the entire group, hepatic margin status (RR 3.2; p < 0.001) and age > 65 years (RR 1.6; p < 0.01) were associated with poorer survival. In the subgroup of patients after neoCTX (n = 106), only the resection margin was an independent predictor of survival (p < 0.001).

Conclusion

In patients with isolated colorectal liver metastases undergoing resection, the hepatic margin status was the strongest independent prognostic factor. This effect was also present after neoadjuvant chemotherapy for CLM.

     

Side-to-end vs. straight stapled colorectal anastomosis after low anterior resection: results of randomized clinical trial

Aim

The aim of this study is to compare surgical, functional, physiologic outcomes and QOL after low anterior resection (LAR) with andside-to-end or straight colorectal anastomosis.

Method

Between 2012 and 2015, 86 patients with mid and low rectal tumors were enrolled into randomized trial. Wexner score, number of defecations, use of antidiarrheal medicine or laxatives, enemas, pads, episodes of nocturnal incontinence, and urgency were recorded. The Fecal Incontinence Quality of Life (FIQL) scale was used for assessment of QOL. Anal manometry and volumetric examination were performed.

Results

Six patients were excluded from the study. There was no mortality. The morbidity rate was 6 (14.6 %) for side-to-end vs. 8 (20.0 %) for straight anastomosis (p?=?0.57). The median Wexner score was 5 vs. 6 (p?=?0.033), 4 vs. 5 (p?=?0.006), and 2 vs. 3 (p?=?0.1) at 1, 3, and 6 months after stoma reversal, respectively. Side-to-end anastomosis resulted in a fewer mean numbers of bowel movements per day at the same check points of follow-up: 5.8?±?0.14 vs. 6.4?±?0.15 (p?=?0.006), 3.7?±?0.1 vs. 4.2?±?0.1 (p?=?0.003), and 2.5?±?0.1 vs. 3.0?±?0.10 (p?=?0.0002), correspondingly. Maximal tolerated volume was higher for side-to-end anastomosis at 3 and 6 months of follow-up: 152.0 vs. 137.8 cm³ (p?=?0.002) and 180.5 vs. 167.0 cm³ (p?=?0.006), respectively. Better FIQL score was found at 1 and 3 months in the side-to-end group.

Conclusion

Better functional outcomes and QOL were observed in a short period after stoma closure, but at 6 months of follow-up, the only benefit of side-to-end anastomosis was a lower number of bowel movements.

     

Dual treatment of acute HCV infection in HIV co-infection: influence of HCV genotype upon treatment outcome

Purpose

With DAAs still only being licensed for chronic HCV infection, the ongoing epidemic of acute hepatitis C (AHC) infection among MSM highlights the need to identify factors allowing for optimal HCV treatment outcome.

Methods

303 HIV-infected patients from 4 European countries with diagnosed acute HCV infection were treated early with pegylated interferon (pegIFN) and ribavirin (RBV) (n = 273) or pegylated interferon alone (n = 30).

Results

All patients were male, median age was 39 years. Main routes of transmission were MSM (95 %) and IVDU (3 %). 69 % of patients were infected with HCV GT 1, 4.3 % with GT 2, 10.6 % with GT 3, 16.1 % with GT 4. Overall SVR rate was 69.3 % (210/303). RVR (p ≤ 0.001), 48-w treatment duration (p ≤ 0.001) and GT 2/3 (p = 0.024) were significantly associated with SVR. SVR rates were significantly higher in HCV GT 2/3 receiving pegIFN and RBV (33/35) when compared with pegIFN mono-therapy (6/10) (94 % vs. 60 % respectively; p = 0.016). In multivariate analysis, pegIFN/RBV combination therapy (p = 0.017) and rapid virological response (RVR) (p = 0.022) were significantly associated with SVR in HCV GT 2/3. In HCV GT 1/4, RVR (p ≤ 0.001) and 48-w treatment duration (p ≤ 0.001) were significantly associated with SVR.

Conclusions

Treatment of AHC GT 2 and 3 infections with pegIFN/RBV is associated with higher SVR rates suggesting different cure rates depending on HCV genotype similar to the genotype effects seen previously in chronic HCV under pegIFN/RBV. With pegIFN/RBV still being the gold standard of AHC treatment and in light of cost issues around DAAs and very limited licensed interferon-free DAA treatment options for chronic HCV GT 3 infection AHC GT 3 patients might benefit most from early interferon-containing treatment.

     

The concentration of programmed cell death-ligand 1 in the peripheral blood is a useful biomarker for esophageal squamous cell carcinoma

Background

We determined the serum concentrations of Programmed cell death-1 (PD-1) and its ligands (PD-L1 and PD-L2) in patients with esophageal squamous cell carcinoma (ESCC).

Methods

Blood samples were collected from 85 patients with histologically proved ESCC. Serum levels of PD-1, PD-L1, and PD-L2 were measured using enzyme linked immunosorbent assays. Correlations between serum PD-1, PD-L1, and PD-L2 concentration and tumor depth, number of lymph node metastases, organ metastasis status, or disease stage were assessed and five-year survival rates according to clinicopathological characteristics were calculated.

Results

The concentration of PD-1 was not differed according to tumor progression. On the other hand, the average concentration of PD-L1 in patients with T3/T4 disease was 15.6 (12.2–18.3) pg/mL (25–75%), and this was significantly higher than that in patients with Tis/T1/T2 disease (p = 0.020). Similarly, PD-L1 levels were significantly higher in patients with positive lymph nodes than in cases with negative lymph node involvement (p = 0.006) and were higher in patients with organ metastasis (p = 0.123) and in more advanced stage (p = 0.006). Similar tendency was observed regarding PD-L2 concentrations. PD-L2 concentration was higher in T3, T4 cases (p = 0.008), in LN positive cases (p = 0.032), and in more advanced stage (p = 0.024).

Conclusion

Our data showed that a concentration of PD-L1 in peripheral blood was high in advanced cancer and high concentration of PD-L1 predicted disease progression and also poor survival in patients with ESCC.

     

Obstructive sleep apnea does not impair cardiorespiratory responses to progressive exercise performed until exhaustion in hypertensive elderly

Background

Elderly people have a high prevalence to systemic arterial hypertension (SAH) and obstructive sleep apnea (OSA). Both comorbidities are closely associated and inflict damage on cardiorespiratory capacity.

Methods

In order to assess cardiorespiratory responses to the cardiopulmonary exercise test (CPET) among hypertensive elderly with OSA, we enrolled 28 subjects into two different groups: without OSA (No-OSA: apnea/hypopnea index (AHI) < 5 events/h; n = 15) and with OSA (OSA: AHI ≥ 15 events/h; n = 13). All subjects underwent CPET and polysomnographic assessments. After normality and homogeneity evaluations, independent t test and Pearson’s correlation were performed. The significance level employed was p ≤ 0.05.

Results

Hypertensive elderly with OSA presented lower heart rate recovery (HRR) in the second minute (HRR₂) in relation to the No-OSA group. A negative correlation between AHI and ventilation (VE) (r = ?0.63, p = 0.02) was found in polysomnography and CPET data comparisons, and oxygen saturation (O₂S) levels significantly correlated with VE/VCO_2slope (r = 0.66, p = 0.01); in addition, No-OSA group presented a positive correlation between oxygen consumption and O₂S (r = 0.66, p = 0.01), unlike the OSA group.

Conclusions

OSA does not affect the CPET variables in hypertensive elderly, but it attenuates the HRR₂. The association between O₂S during sleep with ventilatory responses probably occurs due to the adaptations in the oxygen transport system unleashed via mechanical respiratory feedback; thus, it has been identified that OSA compromises the oxygen supply in hypertensive elderly.

     

Management of bloodstream infections by infection specialists in France and Germany: a cross-sectional survey

Introduction

Bloodstream infections (BSI) are frequent infections worldwide. Our objective was to explore variation in the management of patients with BSI by infection specialists in France and Germany.

Methods

This work is part of an international ESCMID cross-sectional internet-based questionnaire survey that was opened from December 2016 to February 2017. All hospital-based infection specialists, senior or trainees, giving at least weekly advice on positive blood cultures could participate. Their practices were evaluated using six clinical vignettes presenting an uncomplicated BSI due to different pathogens.

Results

A hundred and ninety-six professionals (125 from Germany and 71 from France) participated. Systematic expert advice for positive blood cultures was more often available in Germany as compared with France (73 vs. 56%, p = 0.004). In Germany, the professional providing the expert advice was more often a microbiologist or a pharmacist as compared with France (p = 0.001 and p = 0.037, respectively) where it was more often an infectious diseases specialist. Fewer German respondents reported to advise systematic IV-oral switch of antibiotic therapy. German respondents also recommended less often combination therapy: for example for Enterococcus faecalis (64 vs. 43%, p = 0.015), ESBL E. coli (94 vs. 67%, p < 0.001) and Pseudomonas aeruginosa (76 vs. 37%, p < 0.001). Overall, management of candidaemia was more often compliant with the IDSA guidelines in France as compared with Germany, but no difference was noted for MRSA bacteraemia.

Conclusion

Our survey shows that wide variations exist between two neighboring countries in the recommendations by infection specialists for the management of BSI. International guidelines are needed.