Frailty has a stronger association with inflammation than age in older veterans

Background

Upregulation of pro-inflammatory cytokines has not only been associated with increased morbidity and mortality in older adults but also has been linked to frailty. In the current study we aimed to compare the relative relationship of age and frailty on inflammation and thrombosis in older veterans.

Results

We analyzed 117 subjects (age range 62–95 years; median 81) divided into 3 cohorts: non-frail, pre-frail and frail based on the Fried phenotype of frailty. Serum inflammatory markers were determined using commercially available ELISA kits. Frail and pre-frail (PF) subjects had higher levels than non-frail (NF) subjects of IL-6 (NF vs. PF: p?=?0.002; NF vs. F: p?<?0.001), TNFR1 (NF vs. F: p?=?0.012), TNFRII (NF vs. F: 0.002; NF vs. PF: p?=?0.005) and inflammatory index: = 0.333*log(IL-6)?+?0.666*log(sTNFR1) (NF vs. F: p?=?0.009; NF vs. PF: p?<?0.001). Frailty status explained a greater percent of variability in markers of inflammation than age: IL-6 (12 % vs. 0.3 %), TNFR1 (5 % vs. 4 %), TNFR2 (11 % vs. 6 %), inflammatory index (16 % vs. 8 %). Aging was significantly associated with higher fibrinogen (p?=?0.04) and D-dimer levels (p?=?0.01) but only among NF subjects.

Conclusion

In conclusion, these data suggest that among older veterans, frailty status has a stronger association with inflammation and the inflammatory index than age does. Larger studies, in more diverse populations are needed to confirm these findings.

     

Sex-related differences in the associations between plasma free fatty acid levels and clinical features in patients with hypertrophic cardiomyopathy

Background

Previous studies have indicated that inefficient energy utilization may play a pivotal role in hypertrophic cardiomyopathy (HCM). However, whether plasma free fatty acid (FFA), a main energy substrate of heart, has an effect on HCM remains unclear. Besides, several studies have suggested sex-related differences in HCM features and FFA metabolism. Here, we aimed to explore the association between plasma FFA levels and HCM and potential effects of sex on this relation.

Methods

A total of 412 patients (age 47.8?±?12.7 years, 243 males (59.0%)) with HCM were recruited. Complete medical history was collected. Echocardiography and cardiovascular magnetic resonance imaging (CMRI) were performed. Fasting plasma FFA was determined by clinical laboratory. Left ventricular mass (LVM), maximum wall thickness (MWT), and left atrium diameter (LAD) were assessed with CMRI.

Results

The median FFA levels were 0.38 (interquartile range (IQR) 0.27–0.52) mmol/L in men and 0.40 (IQR 0.30–0.59) mmol/L in women. The FFA levels were significantly lower in men compared with those in women (p?=?0.005). Compared with women, men had greater LVM index (LVMI) (96.8?±?37.6 vs. 78.6?±?31.5 g/m², p?<?0.001). FFA levels in male patients correlated positively with LVM, LVMI, LAD, cholesterol levels, high-density lipoprotein-cholesterol (HDL-C) levels, heart rate, and systolic blood pressure (SBP). However, none of these variables were significantly associated with sqrt (FFA) in female patients except a borderline correlation of LAD (p?=?0.050). Multiple linear regression analysis was performed in male patients and revealed that HDL-C (β?=?0.191, p?=?0.002), heart rate (β?=?0.182, p?=?0.004), SBP (β?=?0.167, p?=?0.007), LVMI (β?=?0.132, p?=?0.032), and LAD (β?=?0.165, p?=?0.009) were independently associated with increasing FFA levels.

Conclusions

In patients with HCM, LVMI, LAD, HDL-C, SBP, and heart rate were independently associated with increasing plasma FFA levels in males, whereas not in females. These results suggest that sex may affect the pathogenesis of HCM through influencing FFA metabolism. And these sex-related differences should be taken into account in therapeutic approaches to influence myocardial FFA metabolism in HCM.

     

Tumour infiltrating lymphocytes correlate with improved survival in patients with oesophageal adenocarcinoma

Background

Oesophageal adenocarcinoma (OAC) is increasingly common in the west, and survival remains poor at 10–15 % at 5 years. Immune responses are increasingly implicated as a determining factor of tumour progression. The ability of lymphocytes to recognise tumour antigens provides a mechanism for a host immune attack against cancer providing a potential treatment strategy.

Materials and Methods

Tumour infiltrating lymphocytes (TILs: CD3+, CD4+, CD8+ and FOXp3+) were assessed by immunohistochemistry using tissue microarrays in a contemporary and homogeneous cohort of OAC patients (n = 128) undergoing curative treatment.

Results

Multivariate analysis identified three independent prognostic factors for improved cancer-specific survival (CSS): increased CD8+ TILs (p = 0.003), completeness of resection (p < 0.0001) and lower pathological N stage (p < 0.0001). Independent prognostic factors for favourable disease-free survival included surgery-only treatment (p = 0.015), completeness of resection (p = 0.001), increased CD8+ TILs (p < 0.0001) and reduced pathological N stage (p < 0.0001). Higher levels of TILs in the pathological specimen were associated with significant pathological response to neoadjuvant chemotherapy (NAC). On multivariate analysis increased levels of CD4+ (p = 0.017) and CD8+ TILs (p = 0.005) were associated with significant local tumour regression and lymph node downstaging, respectively.

Discussion

Our results establish an association of TILs and survival in OAC, as seen in other solid tumours, and identify particular TIL subsets that are present at higher levels in patients who responded to NAC compared to non-responders. These findings highlight potential therapeutic strategies in EAC based on utilising the host immunological response and highlight the immune responses biomarker potential.

     

Prevalence of blood type A and risk of vascular complications following transcatheter aortic valve implantation

Objectives

To assess the prevalence of blood type A among patients referred for transcatheter aortic valve implantation (TAVI) and whether it is related to vascular complications.

Backgrounds

Vascular complications following TAVI are associated with adverse outcomes. Various blood types, particularly type A, have been shown to be more prevalent in cardiovascular diseases and to be related to prognosis.

Methods

The prevalence of various blood types in a cohort of 491 consecutive patients who underwent TAVI was compared with a control group of 6500 consecutive hospitalised patients. The prevalence and predictors of vascular complications and bleeding events were evaluated in the blood type A group and were compared with non-type A patients.

Results

The mean age of TAVI patients was 83?±?6 years, and 40?% were males. Patients were divided into two groups: blood type A (n?=?220) and non-type A (n?=?271). Type A was significantly more prevalent in the TAVI group than in the control group (45 vs. 38?%, p?=?0.023). Compared with the non-type A group, patients with blood type A had more major and fatal bleeding (14.5 vs. 8.1?%, p?=?0.027) and more vascular complications (any vascular complication: 24.5 vs. 15.9?% p?=?0.016; major vascular complications: 12.3 vs. 7?% p?=?0.047). In a multivariable analysis, blood type A emerged as a significant and independent predictor for vascular complications and bleeding events.

Conclusions

Blood type A is significantly more prevalent in TAVI patients than in the general population and is related to higher rates of vascular and bleeding complications.

     

Performance in daily activities,cognitive impairment and perception in multiple sclerosis patients and their caregivers

Background

The relationship between cognitive assessment results in multiple sclerosis (MS) and performance in daily activities (DAs) remains unclear. Our study aimed to evaluate the relationship between cognitive functions (CF) measured by tests, performance in DAs, and the perception of CF in patients and their caregivers (CG) in MS.

Methods

The Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) battery was used to evaluate cognitive status. We created an ad hoc questionnaire (DaQ) to assess performance in DAs not requiring specific motor skills. We used the Multiple Sclerosis Neuropsychological Questionnaire (MSNQ) to measure each patient self-judgment and caregiver’s perception of CF.

Results

Forty-nine patients and their caregivers were included in the study. Significant correlations were found between the BICAMS and the DaQ (Symbol Digit Modalities Test (SDMT): r?=???0.48, p?<?0.001; California Verbal Learning Test (CVLT): r?=???0.33, p?=?0.01; Brief Visual Memory Test (BVMT-R): r?=???0.42; p?=?0.002); patients self-judgment (SDMT: r?=???0.38, p?=?0.004; CVLT: r?=???0.26, p?=?0.03); caregiver perception of patient’s CF (SDMT: r?=???0.52, p?<?0.001; CVLT: r?=???0.3, p?=?0.01; BVMT-R: r?=???0.42, p?=?0.002). The difference in perception between the patients and their caregivers was related to patient age (p?=?0.001) and severity of cognitive impairment (p?=?0.03).

Conclusions

Cognitive assessment results show a significant correlation with performance in daily activities and with patients and, especially, caregiver perception of cognitive impairment. These data support the importance of a routine evaluation of cognitive function in MS that includes an anamnestic evaluation of patients, and, when possible, consideration of the caregiver’s point of view.

     

Different determinants of exercise capacity in HFpEF compared to HFrEF

Background

Quality of life is as important as survival in heart failure (HF) patients. Controversies exist with regards to echocardiographic determinants of exercise capacity in HF, particularly in patients with preserved ejection fraction (HFpEF). The aim of this study was to prospectively examine echocardiographic parameters that correlate and predict functional exercise capacity assessed by 6 min walk test (6-MWT) in patients with HFpEF.

Methods

In 111 HF patients (mean age 63?±?10 years, 47% female), an echo-Doppler study and a 6-MWT were performed in the same day. Patients were divided into two groups based on the 6-MWT distance (Group I: ≤ 300 m and Group II: >300 m).

Results

Group I were older (p?=?0.008), had higher prevalence of diabetes (p?=?0.027), higher baseline heart rate (p?=?0.004), larger left atrium - LA (p?=?0.001), longer LV filling time - FT (p?=?0.019), shorter isovolumic relaxation time (p?=?0.037), shorter pulmonary artery acceleration time - PA acceleration time (p?=?0.006), lower left atrial lateral wall myocardial velocity (a’) (p?=?0.018) and lower septal systolic myocardial velocity (s’) (p?=?0.023), compared with Group II.Patients with HF and reduced EF (HFrEF) had lower hemoglobin (p?=?0.007), higher baseline heart rate (p?=?0.005), higher NT-ProBNP (p?=?0.001), larger LA (p?=?0.004), lower septal s’, e’, a’ waves, and septal mitral annular plane systolic excursion (MAPSE), shorter PA acceleration time (p?<?0.001 for all), lower lateral MAPSE, higher E/A & E/e’, and shorter LVFT (p?=?0.001 for all), lower lateral e’ (p?=?0.009), s’ (p?=?0.006), right ventricular e’ and LA emptying fraction (p?=?0.012 for both), compared with HFpEF patients.In multivariate analysis, only LA diameter [2.676 (1.242–5.766), p?=?0.012], and diabetes [0.274 (0.084–0.898), p?=?0.033] independently predicted poor 6-MWT performance in the group as a whole. In HFrEF, age [1.073 (1.012–1.137), p?=?0.018] and LA diameter [3.685 (1.348–10.071), p?=?0.011], but in HFpEF, lateral s’ [0.295 (0.099–0.882), p?=?0.029], and hemoglobin level [0.497 (0.248–0.998), p?=?0.049] independently predicted poor 6-MWT performance.

Conclusions

In HF patients determinants of exercise capacity differ according to severity of overall LV systolic function, with left atrial enlargement in HFrEF and longitudinal systolic shortening in HFpEF as the the main determinants.

     

Analysis of cardiovascular mortality,bleeding, vascular and cerebrovascular events in patients with atrial fibrillation vs. sinus rhythm undergoing transfemoral Transcatheter Aortic Valve Implantation (TAVR)

Background

Transcatheter aortic valve replacement (TAVR) has been demonstrated to be an established therapy for high-risk, inoperable patients with severe symptomatic aortic valve stenosis. For patients with moderate surgical risk, TAVR is equivalent to conventional aortic valve surgery. However, atrial fibrillation (AF) is also present in many of these patients, thus requiring post-implantation oral anticoagulation therapy in addition to the inhibition of thrombocyte aggregation, which poses the risk of bleeding complications. The aim of our work was to investigate the influence of AF on mortality and the occurrence of bleeding, vascular and cerebrovascular complications related to TAVR according to the VARC-2 criteria.

Methods

Two hundred eighty-three patients who underwent TAVR between March 2010 and April 2016 were retrospectively examined. In total, 257 patients who underwent transfemoral access were included in this study. The mean patient age was 81?±?6 years, 54.1% of the patients were women, and 42.4% had pre-interventional AF.

Results

Compared to patients with sinus rhythm (SR, n?=?148), patients with AF (n?=?109) had an almost three-fold higher incidence of major vascular complications (AF 14.7% vs. SR 5.4%, p?=?0.016) and life-threatening bleeding (AF 11.9% vs. SR 4.1%, p?=?0.028) during the first 30 post-procedural days. However, the rate of cerebrovascular complications (AF 3.7% vs. SR 2.7%, p?=?0.726) did not significantly differ between the two groups. Overall mortality was significantly higher in patients with AF during the first month (AF 8.3% vs. SR 2.0%, p?=?0.032) and the first year (AF 28.4% vs. SR 15.3%; p?=?0.020) following TAVR.

Conclusion

Patients with AF had significantly more severe bleeding complications after TAVR, which were significantly related to mortality. Future prospective randomized studies must clarify the optimal anticoagulation therapy for patients with AF after TAVR.

Trial registration

DRKS00011798 on DRKS (Date 17.03.2017).

     

Ex vivo and in vivo T cell-depleted allogeneic stem cell transplantation in patients with acute myeloid leukemia in first complete remission resulted in similar overall survival: on behalf of the ALWP of the EBMT and the MSKCC

Background

Graft-versus-host disease (GVHD) is one of the leading causes of non-relapse mortality and morbidity after allogeneic hematopoietic stem cell transplantation (allo-HCT).

Methods

We evaluated the outcomes of two well-established strategies used for GVHD prevention: in vivo T cell depletion using antithymocyte globulin (ATG) and ex vivo T cell depletion using a CD34-selected (CD34+) graft. A total of 525 adult patients (363 ATG, 162 CD34+) with intermediate or high-risk cytogenetics acute myeloid leukemia (AML) in first complete remission (CR1) were included. Patients underwent myeloablative allo-HCT using matched related or unrelated donors.

Results

Two-year overall survival estimate was 69.9% (95% CI, 58.5–69.4) in the ATG group and 67.6% (95% CI, 60.3–74.9) in the CD34+ group (p?=?0.31). The cumulative incidence of grade II–IV acute GVHD and chronic GVHD was higher in the ATG cohort [HR 2.0 (95% CI 1.1–3.7), p?=?0.02; HR 15.1 (95% CI 5.3–42.2), p?<?0.0001]. Parameters associated with a lower GVHD-free relapse-free survival (GRFS) were ATG [HR 1.6 (95% CI 1.1–2.2), p?=?0.006], adverse cytogenetic [HR 1.7 (95% CI 1.3–2.2), p?=?0.0004], and the use of an unrelated donor [HR 1.4 (95% CI 1.0–1.9), p?=?0.02]. There were no statistical differences between ATG and CD34+ in terms of relapse [HR 1.52 (95% CI 0.96–2.42), p?=?0.07], non-relapse mortality [HR 0.96 (95% CI 0.54–1.74), p?=?0.90], overall survival [HR 1.43 (95% CI 0.97–2.11), p?=?0.07], and leukemia-free survival [HR 1.25 (95% CI 0.88–1.78), p?=?0.21]. Significantly, more deaths related to infection occurred in the CD34+ group (16/52 vs. 19/112, p?=?0.04).

Conclusions

These data suggest that both ex vivo CD34-selected and in vivo ATG T cell depletion are associated with a rather high OS and should be compared in a prospective randomized trial.

     

Association between chronological depressive changes and physical symptoms in postoperative pancreatic cancer patients

Background

Pancreatic cancer (PC) has poorer prognosis and higher surgical invasiveness than many other cancers, with associated psychiatric symptoms including depression and anxiety. Perioperative depression has not been investigated in PC patients regarding surgical stress and relevant interventions.

Methods

We evaluated chronological depressive changes and subjective physical symptoms in surgically treated PC patients preoperatively and at 3 and 6 months postoperatively.Enrolled patients undergoing pancreatic tumor surgery completed questionnaires based on the Self-Rating Depression Scale (SDS) and Functional Assessment of Cancer Therapy for Patients with Hepatobiliary Cancer (FACT-Hep) preoperatively, and at 3 and 6 months postoperatively. Responses were analyzed with JMP® Pro using one-way and two-way ANOVA, Spearman’s rank correlation coefficient, and multiple regression analysis.

Results

Malignancy was diagnosed in 73 of 101 patients postoperatively; SDS score was significantly higher in these patients than in those with benign tumors at all timepoints: malignant/benign, 41.8/37.9 preoperatively (p?=?0.004); 43.5/37.8 3 months postoperatively (p?=?0.006); and 42.9/37.7 6 months postoperatively (p?=?0.020). SDS scores were significantly higher in patients <?65 years old with malignancy at 3 months than at 6 months postoperatively (44.6/42.5, p?=?0.046) and in patients with malignancy who underwent pancreaticoduodenectomy at 3 months postoperatively than preoperatively (43.4/41.1; p?=?0.028). SDS scores moderately correlated with 8 physical symptom-related FACT-Hep items 3 months postoperatively (p?<?0.05), showing low-to-moderate correlation with 16 physical symptom-related FACT-Hep items at 6 months postoperatively (p?<?0.05). Multiple regression analysis of FACT-Hep symptoms significantly correlated with SDS scores revealed the following significant variables: “lack of energy” (p?<?0.000) and “pain” (p?=?0.018) preoperatively (R²?=?0.43); “able to perform usual activities” (p?=?0.031) and “lack of energy” (p?<?0.000) at 3 months postoperatively (R²?=?0.51); and “stomach swelling or cramps” (p?=?0.034) and “bowel control” (p?=?0.049) at 6 months postoperatively (R²?=?0.52).

Conclusions

PC patients experience persistently high levels of depression preoperatively through 6 months postoperatively, with associated subjective symptoms including pain and gastrointestinal symptoms.

Trial registration

UMIN Clinical Trials Registry 000009592, Registered 20 December 2012.

     

<Emphasis Type="Italic">ABI3</Emphasis> and <Emphasis Type="Italic">PLCG2</Emphasis> missense variants as risk factors for neurodegenerative diseases in Caucasians and African Americans

Background

Rare coding variants ABI3_rs616338-T and PLCG2_rs72824905-G were identified as risk or protective factors, respectively, for Alzheimer’s disease (AD).

Methods

We tested the association of these variants with five neurodegenerative diseases in Caucasian case-control cohorts: 2742 AD, 231 progressive supranuclear palsy (PSP), 838 Parkinson’s disease (PD), 306 dementia with Lewy bodies (DLB) and 150 multiple system atrophy (MSA) vs. 3351 controls; and in an African-American AD case-control cohort (181 AD, 331 controls). 1479 AD and 1491 controls were non-overlapping with a prior report.

Results

Using Fisher’s exact test, there was significant association of both ABI3_rs616338-T (OR?=?1.41, p?=?0.044) and PLCG2_rs72824905-G (OR?=?0.56, p?=?0.008) with AD. These OR estimates were maintained in the non-overlapping replication AD-control analysis, albeit at reduced significance (ABI3_rs616338-T OR?=?1.44, p?=?0.12; PLCG2_rs72824905-G OR?=?0.66, p?=?0.19). None of the other cohorts showed significant associations that were concordant with those for AD, although the DLB cohort had suggestive findings (Fisher’s test: ABI3_rs616338-T OR?=?1.79, p?=?0.097; PLCG2_rs72824905-G OR?=?0.32, p?=?0.124). PLCG2_rs72824905-G showed suggestive association with pathologically-confirmed MSA (OR?=?2.39, p?=?0.050) and PSP (OR?=?1.97, p?=?0.061), although in the opposite direction of that for AD. We assessed RNA sequencing data from 238 temporal cortex (TCX) and 224 cerebellum (CER) samples from AD, PSP and control patients and identified co-expression networks, enriched in microglial genes and immune response GO terms, and which harbor PLCG2 and/or ABI3. These networks had higher expression in AD, but not in PSP TCX, compared to controls. This expression association did not survive adjustment for brain cell type population changes.

Conclusions

We validated the associations previously reported with ABI3_rs616338-T and PLCG2_rs72824905-G in a Caucasian AD case-control cohort, and observed a similar direction of effect in DLB. Conversely, PLCG2_rs72824905-G showed suggestive associations with PSP and MSA in the opposite direction. We identified microglial gene-enriched co-expression networks with significantly higher levels in AD TCX, but not in PSP, a primary tauopathy. This co-expression network association appears to be driven by microglial cell population changes in a brain region affected by AD pathology. Although these findings require replication in larger cohorts, they suggest distinct effects of the microglial genes, ABI3 and PLCG2 in neurodegenerative diseases that harbor significant vs. low/no amyloid ß pathology.

     

Changes in automated external defibrillator use and survival after out-of-hospital cardiac arrest in the Nijmegen area

Purpose

Out-of-hospital cardiac arrests (OHCAs) are a major healthcare problem. Over the years, several initiatives have contributed to more lay volunteers providing cardiopulmonary resuscitation (CPR) and increased use of automated external defibrillators (AEDs) in the Netherlands. As part of a quality and outcomes program, we registered bystander CPR, AED use and outcome in the Nijmegen area.

Methods

Prospective resuscitation registry with a study cohort of non-traumatic OHCA cases from 2013–2016 and historical controls from 2008–2011. In line with previous reports, we studied patients transported to the hospital (Radboudumc, Nijmegen, the Netherlands) and excluded arrests witnessed by the emergency medical service (EMS). Primary outcomes were return of spontaneous circulation (ROSC) and survival to discharge.

Results

In the study cohort (n?=?349) the AED was attached more often than in the historical cohort (n?=?180): 46% vs. 23% and the proportion of bystander CPR was higher: 78% vs. 63% (both p?<?0.001). A higher proportion of patients received an AED shock (39% vs. 15%, p?<?0.001) and the number of required shocks by the EMS was lower (2 vs. 4, p?=?0.004). Survival to discharge was higher (47% vs. 33%, p?=?0.002) without differences in ROSC. The survival benefit was restricted to patients with a shockable initial rhythm. In both cohorts, bystander CPR and AED use were independently associated with survival.

Conclusion

In patients admitted after OHCA, survival to discharge has markedly improved to 40–50%, comparable with other Dutch registries. As increased bystander CPR and the doubled use of AEDs seem to have contributed, all civilian-based resuscitation initiatives should be encouraged.

     

Prognostic significance of mucin expression profiles in breast carcinoma with signet ring cells: a clinicopathological study

Background

Signet ring cells (SRCs) often accompany gastrointestinal carcinoma, referred to as SRC carcinoma; however, breast cancers containing SRCs have not been well characterized, leaving the prognostic significance of SRCs undetermined. We have described clinicopathological characteristics of patients with breast cancer containing SRCs in relation to the expression levels of MUC1, MUC2, MUC4, MUC5AC, and MUC6.

Methods

Twenty-two breast cancer cases with variable degrees of SRC population were retrospectively studied. Each case was categorized as high (>31 %) or low (<30 %) SRC tumor. The SRCs were morphologically classified into the intra-cytoplasmic lumen (ICL) type, or the non-ICL type. The expression levels of MUC1, MUC2, MUC4, MUC5AC and MUC6 were determined immunohistochemically. Depending on its subcellular localization, MUC1 was categorized as the luminal and cytoplasmic (LC) type, or the cytoplasmic with circumferential membranous accentuation (CM) type. These histological findings were compared with other clinicopathological parameters.

Results

The series consisted of invasive ductal carcinoma (n?=?9), invasive lobular carcinoma (n?=?9), and mucinous carcinoma (n?=?4) cases. The SRC population accounted for 8–81 % of the tumor cells. Eight cases had ICL type SRCs, and the remaining 14 had non-ICL type SRCs. Neither the high (n?=?12) and low (n?=?10) percentage of SRCs, nor the SRC types affected the clinicopathological parameters. In the low MUC1 group (n?=?11), larger tumors, higher nuclear grade, lymph node metastasis, and negativity for estrogen receptor was more frequently identified compared to the high MUC1 group (n?=?11; p?=?0.01, p?=?0.002, p?=?0.008, and p?=?0.02, respectively). The CM group (n?=?7) had more patients with large-sized tumors, lymph node metastasis, lymphovascular invasion, and higher Ki67 indices than the LC group (n?=?15; p?=?0.04, p?=?0.001, p?=?0.006, and p?=?0.03, respectively). The expression levels of MUC2, MUC4, MUC5AC, and MUC6 showed no clinicopathological significance. Two patients with low MUC1 expression and CM patterns had tumor recurrence, resulting in death, while all the other patients survived without recurrence.

Conclusion

Our results demonstrate that in breast cancers containing SRCs, low MUC1 expression and/or its CM subcellular localization patterns are associated with unfavorable clinicopathological factors. The utility of MUC1 expression as a prognostic marker remains to be verified in future studies.

     

Influence of permanent pacemaker implantation after transcatheter aortic valve implantation with new-generation devices

Objective

Permanent pacemaker implantation (PPMI) after transcatheter aortic valve implantation (TAVI) is the most common complication after the procedure. PPMI rates remain high with the new-generation TAVI devices despite improved outcomes concerning paravalvular aortic regurgitation and vascular access complications. However, the impact of PPMI on mortality and clinical outcome is still a matter of debate, and data with new-generation devices on this matter are scarce. Therefore, we sought to analyse the influence of PPMI in patients treated with the new-generation devices on one-year outcome.

Methods

We enrolled 612 consecutive patients without prior pacemaker undergoing transfemoral TAVI with the new-generation devices. Patients with or without PPMI were compared with respect to clinical outcome within one year.

Results

PPMI was performed in 168 patients (24.4% of the overall study population). There was no significant difference in one-year outcome concerning all-cause mortality (PPMI vs. no-PPMI: 12.2% vs. 12.5%, p?=?0.94), rate of major adverse events including cardiac, cerebral or valve-related events and bleeding complications (22.1% vs. 24.5%, p?=?0.55) or need for rehospitalisation due to cardiac symptoms (16.1% vs. 18.1%, p?=?0.63). In patients with reduced ejection fraction (<45%) there was also no impact of PPMI on one-year mortality (14.3% vs. 15.7%, p?=?0.86). Furthermore, multivariate analysis did not reveal PPMI to be independently associated with one-year mortality (odds ratio 0.94, 95% confidence interval 0.50–1.74, p?=?0.83).

Conclusions

In this large all-comers TAVI population with new-generation devices the need for postprocedural PPMI did not show a statistical significant impact on survival or combined endpoint of major adverse events within one year.

     

Prognostic value of rising mean platelet volume during hospitalization in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention

Background

The prognostic significance of changes in mean platelet volume (MPV) during hospitalization in ST segment elevation myocardial infarction (STEMI) patients underwent primary percutaneous coronary intervention (pPCI) has not been previously evaluated. The aim of this study was to determine the association of in-hospital changes in MPV and mortality in these patients.

Methods

Four hundred eighty consecutive STEMI patients were enrolled in this retrospective study. The patients were grouped as survivors (n?=?370) or non-survivors (n?=?110). MPV at admission, and at 48–72?h was evaluated. Change in MPV (MPV at 48–72?h minus MPV on admission) was defined as ΔMPV.

Results

At follow-up, long-term mortality was 23%. The non-survivors had a high ΔMPV than survivors (0.37 (??0.1–0.89) vs 0.79 (0.30–1.40) fL, p?<? 0.001). A high ΔMPV was an independent predictor of all cause mortality ((HR: 1.301 [1.070–1.582], p?=?0.008). Morever, for long-term mortality, the AUC of a multivariable model that included age, LVEF, Killip class, and history of stroke/TIA was 0.781 (95% CI:0.731–0.832, p?<? 0.001). When ΔMPV was added to a multivariable model, the AUC was 0.800 (95% CI: 0.750–0.848, z?=?2.256, difference p?=?0.0241, Fig. 1). Also, the addition of ΔMPV to a multivariable model was associated with a significant net reclassification improvement estimated at 24.5% (p?=?0.027) and an integrated discrimination improvement of 0.014 (p?=?0.0198).

Conclusions

Rising MPV during hospitalization in STEMI patients treated with pPCI was associated with long-term mortality.

     

Short versus long duration of dual antiplatelet therapy following drug-eluting stents: a meta-analysis of randomised trials

Background

Dual antiplatelet therapy (DAPT) remains the cornerstone therapy in the prevention of ischaemic events following drug-eluting stent (DES) implantation. Mandatory duration of DAPT after DES however, is a matter of debate. We aimed to evaluate safety and efficacy of short-term (up to 6 months) versus long-term (12 months) DAPT after DES implantation.

Methods

We searched PubMed, EMBASE, Cochrane databases, and international meetings for randomised clinical trials (RCTs) comparing short with long DAPT. We performed a systematic review and meta-analysis of major trials with primary outcomes: all-cause death, myocardial infarction, definite or probable stent thrombosis, stroke, and major bleeding event.

Results

Nine RCTs with a total number of 19,099 patients were pooled in the present meta-analysis. When compared with long DAPT, short DAPT was associated with a significant reduction in major bleeding events (0.62% vs. 1.10%, risk ratio (RR) 0.58, 95% confidence interval (CI) 0.39 to 0.86, p?<?0.007, I²?=?21%), whereas all-cause death (1.65% vs. 1.84%, RR 0.90, 95% CI 0.73 to 1.11, p?=?0.34, I2?=?0%), myocardial infarction (1.91% vs. 1.68%, RR 1.14, 95% CI 0.92 to 1.40, p?=?0.23, I2?=?0%), definite or probable stent thrombosis (0.62% vs. 0.47%, RR 1.25, 95% CI 0.84 to 1.86, p?=?0.27, I2?=?0%), and stroke (0.60% vs. 0.67%, RR 0.91, 95% CI 0.63 to 1.31, p?=?0.61, I2?=?0%) were similar.

Conclusions

Short DAPT following DES implantation results in a significant reduction of major bleeding events with no apparent increase in all-cause death, myocardial infarction, stent thrombosis, or stroke. Future dedicated trials should investigate the optimal strategies for patient-tailored DAPT in various subgroups.

     

HCV monoinfection and HIV/HCV coinfection enhance T-cell immune senescence in injecting drug users early during infection

Background

Injecting drug users (IDU) are at premature risk of developing multimorbidity and mortality from causes commonly observed in the elderly. Ageing of the immune system (immune-senescence) can lead to premature morbidity and mortality and can be accelerated by chronic viral infections. Here we investigated the impact of HCV monoinfection and HIV/HCV coinfection on immune parameters in (ex-) IDU. We analyzed telomere length and expression of activation, differentiation and exhaustion markers on T cells at baseline (t?=?1) and at follow-up (t?=?2) (median interval 16.9 years) in IDU who were: HCV mono-infected (n?=?21); HIV/HCV coinfected (n?=?23) or multiple exposed but uninfected (MEU) (n?=?8).

Results

The median time interval between t?=?1 and t?=?2 was 16.9 years. Telomere length within CD4⁺ and CD8⁺ T cells decreased significantly over time in all IDU groups (p?≤?0.012). CD4⁺ T-cell telomere length in HCV mono-infected IDU was significantly reduced compared to healthy donors at t?=?1 (p?<?0.008). HIV/HCV coinfected IDU had reduced CD4⁺ and CD8⁺ T-cell telomere lengths (p?≤?0.002) to healthy donors i at t?=?1. This was related to persistent levels of immune activation but not due to increased differentiation of T cells over time. Telomere length decrease was observed within all T-cell subsets, but mainly found in immature T cells (CD27⁺CD57⁺) (p?≤?0.015).

Conclusions

HCV mono-infection and HIV/HCV coinfection enhance T-cell immune-senescence. Our data suggest that this occurred early during infection, which warrants early treatment for both HCV and HIV to reduce immune senescence in later life.

     

Characterization of diabetes following pancreatic surgery in patients with congenital hyperinsulinism

Background

Congenital hyperinsulinism (CHI) is the most common cause of persistent hypoglycaemia in infancy that leads to unfavourable neurological outcome if not treated adequately. In patients with severe diffuse CHI it remains under discussion whether pancreatic surgery should be performed or intensive medical treatment with the acceptance of recurrent episodes of mild hypoglycaemia is justified. Near-total pancreatectomy is associated with high rates of insulin-dependent diabetes mellitus and exocrine pancreatic insufficiency. Little is known about the management and long-term glycaemic control of CHI patients with diabetes after pancreatic surgery. We searched the German/Austrian DPV database and compared the course of 42 CHI patients with diabetes to that of patients with type 1 diabetes mellitus (T1DM). Study groups were compared at diabetes onset and after a follow-up period of 6.1 [3.3–9.7] (median [interquartile range]) years.

Results

The majority of CHI patients with diabetes were treated with insulin (85.2% [70.9–99.5] at diabetes onset, and 90.5% [81.2–99.7] at follow-up). However, compared to patients with T1DM, significantly more patients in the CHI group with diabetes were treated with conventional insulin therapy (47.8% vs. 24.4%, p?=?0.03 at diabetes onset, and 21.1% vs. 6.4% at follow-up, p?=?0.003), and only a small number of CHI patients were treated with insulin pumps. Daily insulin dose was significantly lower in CHI patients with diabetes than in patients with T1DM, both at diabetes onset (0.3 [0.2–0.5] vs. 0.6?IE/kg/d [0.4–0.8], p?=?0.003) and follow-up (0.8 [0.4–1.0] vs. 0.9 [0.7–1.0] IE/kg/d, p?=?0.02), while daily carbohydrate intake was comparable in both groups. Within the first treatment year, HbA1c levels were significantly lower in CHI patients with diabetes (6.2% [5.5–7.9] vs. 7.2% [6.5–8.2], p?=?0.003), but increased to a level comparable to that of T1DM patients at follow-up. Interestingly, in CHI patients, the risk of severe hypoglycaemia tends to be higher only at diabetes onset (14.8% vs. 5.8%, p?=?0.1).

Conclusions

In surgically treated CHI patients insulin treatment needs to be intensified in order to achieve good glycaemic control. Our data furthermore emphasize the need for improved medical treatment options for patients with diazoxide- and/or octreotide-unresponsive CHI.

     

Subinguinal microsurgical varicocelectomy vs. percutaneous embolization in infertile men: Prospective comparison of reproductive and functional outcomes

Background

Varicocele is a condition characterized by dilated, tortuous veins within the pampiniform venous plexus of the scrotal sac. Presence of varicocele is associated with an increased risk of alteration of semen parameters. The objective of this study was to compare the current standard in varicocele treatment procedures: sub-inguinal microscopic ligation to percutaneous embolization in terms of semen parameters improvement, fertility, and morbidity at the university hospital of Toulouse (France). Seventy six patients with clinical varicocele, alteration of semen parameters and infertility, underwent either procedure (microsurgery in 49 case performed by a single surgeon and embolization in 27 cases) and were prospectively analyzed. Outcome measures were: semen parameters, spontaneous pregnancies, pain, side effects, recovery time and overall satisfaction. All patients were contacted in January 2015 in order to determine reproductive events.

Results

Preoperatively, there was no difference in clinical and biological items between the two groups. Postoperatively, on the overall population, there was a significant improvement of sperm concentration at 3, 6, 9 and 12 months (p?=?<0.001, <0.001, 0.012, 0.018) and sperm motility at 6 months (p?=?0.002). The sperm concentration was higher at 6 months in the percutaneous embolization group (13.42, vs. 8.1×10⁶/ml; p?=?0.043). With a median follow-up of 4 years, 27 pregnancies occurred (spontaneous pregnancy rate of 35.5%).There was no significant difference between procedures on the sperm quality, pregnancy rate, and the overall satisfaction. Patients undergoing percutaneous embolization reported a faster recovery time (p?=?0.002) and less postoperative pain (p?=?0.007).

Conclusion

Our study shows that percutaneous embolization seems to be an equivalent alternative to sub-inguinal microscopic ligation in term of sperm quality improvement, pregnancy rate, and overall satisfaction with a slight advantage on post-operative morbidity.