Plasma NGAL levels in stable kidney transplant recipients and the risk of allograft loss.

BACKGROUND: The objective of this study was to investigate the utility of neutrophil gelatinase-associated lipocalin (NGAL) and calprotectin (CPT) to predict long-term graft survival in stable kidney transplant recipients (KTR). METHODS: A total of 709 stable outpatient KTR were enrolled >2 months post-transplant. The utility of plasma and urinary NGAL (pNGAL, uNGAL) and plasma and urinary CPT at enrollment to predict death-censored graft loss was evaluated during a 58-month follow-up. RESULTS: Among biomarkers, pNGAL showed the best predictive ability for graft loss and was the only biomarker with an area under the curve (AUC) > 0.7 for graft loss within 5 years. Patients with graft loss within 5 years (n = 49) had a median pNGAL of 304 [interquartile range (IQR) 235-358] versus 182 (IQR 128-246) ng/mL with surviving grafts (P < .001). Time-dependent receiver operating characteristic analyses at 58 months indicated an AUC for pNGAL of 0.795, serum creatinine-based Chronic Kidney Disease Epidemiology Collaboration estimated glomerular filtration rate (eGFR) had an AUC of 0.866. pNGAL added to a model based on conventional risk factors for graft loss with death as competing risk (age, transplant age, presence of donor-specific antibodies, presence of proteinuria, history of delayed graft function) had a strong independent association with graft loss {subdistribution hazard ratio (sHR) for binary log-transformed pNGAL [log2(pNGAL)] 3.4, 95% confidence interval (CI) 2.24-5.15, P < .0001}. This association was substantially attenuated when eGFR was added to the model [sHR for log2(pNGAL) 1.63, 95% CI 0.92-2.88, P = .095]. Category-free net reclassification improvement of a risk model including log2(pNGAL) in addition to conventional risk factors and eGFR was 54.3% (95% CI 9.2%-99.3%) but C-statistic did not improve significantly. CONCLUSIONS: pNGAL was an independent predictor of renal allograft loss in stable KTR from one transplant center but did not show consistent added value when compared with baseline predictors including the conventional marker eGFR. Future studies in larger cohorts are warranted.

Relevance of different prognostic scores in primary CNS lymphoma in the era of intensified treatment regimens: A retrospective, multicenter analysis of 174 patients.

OBJECTIVES: Treatment intensification (including consolidative high-dose chemotherapy with autologous stem cell transplantation [HDT-ASCT]) significantly improved outcome in primary central nervous system lymphoma (PCNSL) patients. METHODS: We conducted a multicenter, retrospective analysis of newly diagnosed PCNSL patients, treated with intensified treatment regimens. The following scores were evaluated in terms of overall survival (OS) and progression-free survival (PFS): Memorial Sloan-Kettering Cancer Center (MSKCC), International Extranodal Lymphoma Study Group (IELSG), and three-factor (3F) prognostic score. Further, all scores were comparatively investigated for model quality and concordance. RESULTS: Altogether, 174 PCNSL patients were included. One hundred and five patients (60.3%) underwent HDT-ASCT. Two-year OS and 2-year PFS for the entire population were 73.3% and 48.5%, respectively. The MSKCC (p = .003) and 3F score (p < .001), but not the IELSG score (p = .06), had the discriminatory power to identify different risk groups for OS. In regard to concordance, the 3F score (C-index [0.71]) outperformed both the MSKCC (C-index [0.64]) and IELSG (C-index [0.53]) score. Moreover, the superiority of the 3F score was shown for PFS, successfully stratifying patients in three risk groups, which also resulted in the highest C-index (0.66). CONCLUSION: The comparative analysis of established PCNSL risk scores affirm the clinical utility of the 3F score stratifying the widest prognostic spectrum among PCNSL patients treated with intensified treatment approaches.

Previous antibiotic therapy as independent risk factor for the presence of vancomycin-resistant enterococci in surgical inpatients. Results from a matched case-control study.

BACKGROUND: Investigation of risk factors for the presence of vancomycin-resistant enterococci (VRE) in inpatients on surgical wards and associated intensive care units of a German tertiary care hospital. METHODS: A single-centre retrospective matched case-control study was performed with surgical inpatients admitted between July 2013 and December 2016. Patients with in-hospital detection of VRE later than 48 h after admission were included and comprised 116 VRE-positive cases and 116 VRE-negative matched controls. VRE isolates of cases were typed by multi-locus sequence typing. RESULTS: ST117 was identified as the dominant VRE sequence type. Next to length of stay in hospital or on an intensive care unit and previous dialysis the case-control study revealed previous antibiotic therapy as a risk factor for the in-hospital detection of VRE. The antibiotics piperacillin/tazobactam, meropenem, and vancomycin were associated with the highest risks. After taking into account length of stay in hospital as possible confounder other potential contact-related risk factors such as previous sonography, radiology, central venous catheter, and endoscopy were not significant. CONCLUSIONS: Previous dialysis and previous antibiotic therapy were identified as independent risk factors for the presence of VRE in surgical inpatients.

Randomized Trial of a Supportive Psychotherapy for Parents of Adolescents and Young Adults With Hematologic Malignancies.

BACKGROUND: Cancer regularly disrupts health and developmental trajectories in adolescents and young adults (AYAs). Parents have been shown to have a substantial impact on the health and cancer survivorship activities of AYA patients in the form of symptom management. However, no randomized controlled trial has evaluated a coping support intervention (CSI) program for parents of AYAs with cancer aged 18 to 40 years. PATIENTS AND METHODS: From November 30, 2012, to August 29, 2016, parents of AYAs with hematologic malignancies were randomized in a phase III controlled trial (1:1 ratio, stratified sampling) to either the research-based CSI AYA-Parents group (CSI group; n=82) or the standard care (SC) group (n=70). CSI consisted of 5 sessions to achieve the enhancement of parental adaptive coping as the primary outcome (per the adaptive coping scale of the 28-item Brief COPE, a validated multidimensional self-assessment-questionnaire recommended for clinical cancer research). Measures of adaptive coping, depression, and mental health were collected at pre-CSI (measurement date T1), at the end of the intervention sessions (measurement date T2), and at follow-up (3 months). We calculated mean change scores in outcomes and estimated intervention effect sizes (Cohen's d) for changes from T1 to T2/T3, with 0.2 indicating a small effect, 0.5 a medium effect, and 0.8 a large effect. All statistical tests were 2-sided. RESULTS: In the intention-to-treat analysis, the CSI group significantly improved their adaptive coping compared with the SC group (95% CI, 0.30-2.54; P=.013; d=0.405), whereas adaptive coping in the SC group deteriorated. The CSI group also experienced a significant decrease in depressive symptoms and improved mental health with clinical significance (95% CI, -1.98 to -0.30; P=.008; d=0.433, and 95% CI, -0.19 to 3.97; P=.074; d=0.292, respectively). Sensitivity analyses confirmed the robustness of the main intention-to-treat analysis. CONCLUSIONS: CSI improved effectively adaptive coping and depression in parents of AYAs with hematologic malignancies. It may represent a novel family-based approach in AYA oncology care.

Quantitative normal values of helical flow, flow jets and wall shear stress of healthy volunteers in the ascending aorta.

OBJECTIVES: 4D flow MRI enables quantitative assessment of helical flow. We sought to generate normal values and elucidate changes of helical flow (duration, volume, length, velocities and rotational direction) and flow jet (displacement, flow angle) as well as wall shear stress (WSS). METHODS: We assessed the temporal helical existence (THEX), maximum helical volume (HVmax), accumulated helical volume (HVacc), accumulated helical volume length (HVLacc), maximum forward velocity (maxVfor), maximum circumferential velocity (maxVcirc), rotational direction (RD) and maximum wall shear stress (WSS) as reported elsewhere using the software tool Bloodline in 86 healthy volunteers (46 females, mean age 41 ± 13 years). RESULTS: WSS decreased by 42.1% and maxVfor by 55.7% across age. There was no link between age and gender regarding the other parameters. CONCLUSION: This study provides age-dependent normal values regarding WSS and maxVfor and age- and gender-independent normal values regarding THEX, HVmax, HVacc, HVLacc, RD and maxVcirc. KEY POINTS: • 4D flow provides numerous new parameters; therefore, normal values are mandatory. • Wall shear stress decreases over age. • Maximum helical forward velocity decreases over age.

Use of multivariate distance measures for high-dimensional data in tests for difference, superiority, equivalence and non-inferiority.

Tests based on pairwise distance measures for multivariate sample vectors are common in ecological studies but are usually restricted to two-sided tests for differences. In this paper, we investigate extensions to tests for superiority, equivalence and non-inferiority.

Molecular profiling of pediatric meningiomas shows tumor characteristics distinct from adult meningiomas.

In contrast to adults, meningiomas are uncommon tumors in childhood and adolescence. Whether adult and pediatric meningiomas differ on a molecular level is unclear. Here we report detailed genomic analyses of 37 pediatric meningiomas by sequencing and DNA methylation profiling. Histologically, the series was dominated by meningioma subtypes with aggressive behavior, with 70% of patients suffering from WHO grade II or III meningiomas. The most frequent cytogenetic aberrations were loss of chromosomes 22 (23/37 [62%]), 1 (9/37 [24%]), 18 (7/37 [19%]), and 14 (5/37 [14%]). Tumors with NF2 alterations exhibited overall increased chromosomal instability. Unsupervised clustering of DNA methylation profiles revealed separation into three groups: designated group 1 composed of clear cell and papillary meningiomas, whereas group 2A comprised predominantly atypical meningiomas and group 2B enriched for rare high-grade subtypes (rhabdoid, chordoid). Meningiomas from NF2 patients clustered exclusively within groups 1 and 2A. When compared with a dataset of 105 adult meningiomas, the pediatric meningiomas largely grouped separately. Targeted panel DNA sequencing of 34 tumors revealed frequent NF2 alterations, while other typical alterations found in adult non-NF2 tumors were absent. These data demonstrate that pediatric meningiomas are characterized by molecular features distinct from adult tumors.

Estimated Prevalence of Harmful Alcohol Consumption in Pregnant and Nonpregnant Women in Saxony-Anhalt (NorthEast Germany) Using Biomarkers.

BACKGROUND: Alcohol consumption is commonly accepted in Western societies and is a known risk factor in pregnancy, which could lead to fetal alcohol spectrum disorders (FASDs). Prevalence of alcohol consumption during pregnancy is mostly unknown. Prevalence estimates in publications based on questionnaires are limited by possible underreporting due to social stigmatization. The aim of this study was to estimate the prevalence of harmful alcohol consumption in a large cohort of pregnant women using different biomarkers related to alcohol consumption and compare the findings with those of non-pregnant women METHODS: Routine parameters known to be influenced by alcohol consumption (γ-glutamyltransferase, GGT; carbohydrate-deficient transferrin, CDT/%CDT; mean corpuscular/cell volume, MCV; combined parameter of GGT and %CDT, GGT-CDT) were analyzed in serum samples of 2,182 pregnant women and 743 non-pregnant, age-matched females. Data were tested for (i) differences between pregnant and non-pregnant women and (ii) changes across the 3 trimesters of pregnancy. RESULTS: Prevalence rates differ greatly according to the parameter and cutoff, which reflects the limitations of assessing alcohol consumption with biomarkers. The prevalence of harmful alcohol consumption on the basis of a single or several elevated parameters was 13.8% (95% CI: 12.4 to 15.2) in pregnant women and 18.6% (95% CI: 15.8 to 21.4) in non-pregnant women, though 85.0% of the elevated measurements were attributable to an isolated elevation in %CDT only. Using GGT-CDT as the parameter with the highest specificity according to the literature, the estimated prevalence of harmful alcohol consumption in pregnancy is 0.5% (95% CI: 0.2 to 0.7). CONCLUSION: Estimated prevalence rates differ greatly with respect to the biomarkers and cutoffs used. The use of CDT/%CDT alone appears to overestimate harmful alcohol consumption during pregnancy.

Urinary Neutrophil Gelatinase-Associated Lipocalin/Hepcidin-25 Ratio for Early Identification of Patients at Risk for Renal Replacement Therapy After Cardiac Surgery: A Substudy of the BICARBONATE Trial.

BACKGROUND: Acute kidney injury requiring renal replacement therapy (AKI-RRT) is strongly associated with mortality after cardiac surgery; however, options for early identification of patients at high risk for AKI-RRT are extremely limited. Early after cardiac surgery, the predictive ability for AKI-RRT even of one of the most extensively evaluated novel urinary biomarkers, neutrophil gelatinase-associated lipocalin (NGAL), appears to be only moderate. We aimed to determine whether the NGAL/hepcidin-25 ratio (urinary concentrations of NGAL divided by that of hepcidin-25) early after surgery may compare favorably to NGAL for identification of high-risk patients after cardiac surgery. METHODS: This is a prospective substudy of the BICARBONATE trial, a multicenter parallel-randomized controlled trial comparing perioperative bicarbonate infusion for AKI prevention to usual patient care. At a tertiary referral center, 198 patients at increased kidney risk undergoing cardiac surgery with cardiopulmonary bypass were included into the present study. The primary outcome measure was defined as AKI-RRT. Secondary outcomes were in-hospital mortality and long-term mortality. We compared area under the curve of the receiver operating characteristic (AUC-ROC) of urinary NGAL with that of the urinary NGAL/hepcidin-25 ratio within 60 minutes after end of surgery. We compared adjusted AUC and performed cross-validated reclassification statistics of the (logarithmic) urinary NGAL/hepcidin-25 ratio adjusted to Cleveland risk score/EuroScore, cross-clamp time, age, volume of packed red blood cells, and (logarithmic) urinary NGAL concentration. The association of the NGAL/hepcidin-25 ratio with long-term patient survival was assessed using Cox proportional hazard regression analysis adjusting for EuroScore, aortic cross-clamp time, packed red blood cells and urinary NGAL. RESULTS: Patients with AKI-RRT (n = 13) had 13.7-times higher NGAL and 3.3-times lower hepcidin-25 concentrations resulting in 46.9-times higher NGAL/hepcidin-25 ratio early after surgery compared to patients without AKI-RRT. The NGAL/hepcidin-25 ratio had higher AUC-ROC compared with NGAL for risk of AKI-RRT and in-hospital mortality (unadjusted AUC-ROC difference 0.087, 95% confidence interval [CI], 0.036-0.138, P < .001; 0.082, 95% CI, 0.018-0.146, P = .012). For AKI-RRT, the NGAL/hepcidin-25 ratio increased adjusted category-free net reclassification improvement (cfNRI; 0.952, 95% CI, 0.437-1.468; P < .001) and integrated discrimination improvement (IDI; 0.040, 95% CI, 0.008-0.073; P = .016) but not AUC difference. For in-hospital mortality, the ratio improved AUC of the reference model (AUC difference 0.056, 95% CI, 0.003-0.108; P = .037) and cfNRI but not IDI. The urinary NGAL/hepcidin-25 ratio remained significantly associated with long-term mortality after adjusting for the model covariates. CONCLUSIONS: The urinary NGAL/hepcidin-25 ratio appears to early identify high-risk patients and outperform NGAL after cardiac surgery. Confirmation of our findings in other cardiac surgery centers is now needed.

High incidence of deep vein thrombosis during the treatment of pseudoaneurysms - a retrospective nonrandomized study.

Background: Pseudoaneurysms (PSAs) are concerning complications after arterial invasive interventions. Therapeutic options include manual ultrasound-assisted compression, pressure dressings, surgical intervention and thrombin injection. Compression of neighboring veins is obvious. However, the incidence of deep vein thrombosis (DVT) in patients with PSA has not previously been investigated. Patients and methods: In this retrospective, nonrandomized study 238 patients with PSA were analyzed from 2013 to 2018. In 149 patients, all of the parameters were complete for participating. PSAs were treated according to the local standard therapy with either ultrasound-guided compression followed by compression bandage or thrombin injection. Treatment success was evaluated 24 hours later, and the venous system was examined for the presence of DVT. Results: Peripheral DVT was found in 25.4% patients after ultrasound-assisted compression and subsequent pressure bandages, but only 6.4% of patients had DVT after thrombin injection (p = 0.013). Lower leg veins, particularly veins of the crural muscles, were primarily affected. Significantly more PSAs were successfully treated without the occurrence of DVT in the thrombin injection group compared to the compression group (93.6 vs. 69.0%; p = 0.001). Conclusions: Our study revealed that the use of thrombin injections resulted in a significantly lower rate of postinterventional DVT and a higher total number of successfully treated PSAs compared to compression therapy.

The impact of neuropsychiatric disease on fetal growth: a case-control study.

PURPOSE: To determine the impact of depression, epilepsy and drug abuse during pregnancy on delivery and fetal outcome. Due to the worldwide increasing prevalence of neurological and psychiatric diseases and drug abuse, the number of affected pregnant women is increasing. METHODS: A large-scale retrospective case-control analysis of pregnancies affected by depression, epilepsy or drug abuse with and without medication was conducted in two German perinatal centres between 2013 and 2017. The case group consisted of 706 pregnant women who had a diagnosis of depression, epilepsy or drug abuse vs. 12,574 pregnant women without neuropsychiatric diagnosis (control group). The analysis included the rate of intrauterine growth restriction, birth weight and length, neonatal head circumference. RESULTS: Significant differences in the subgroups were found in the parameters intrauterine growth restriction, birth weight, length and head circumference. Women with epilepsy were affected less often than women with depression and substance abuse. Major differences were found in the group of women with substance abuse. Negative associations were found within the non-pharmacologically managed disease group itself compared to women exposed to medication. CONCLUSION: The present results demonstrated a negative association between maternal neurological or psychiatric disease and pregnancy outcome in the examined parameters. However, the non-pharmacologically treated maternal disease was identified as a risk factor itself.

Flexible transnasal endoscopy with white light or narrow band imaging for the diagnosis of laryngeal malignancy: diagnostic value, observer variability and influence of previous laryngeal surgery.

PURPOSE: Flexible transnasal endoscopy is a common examination technique for the evaluation of laryngeal lesions, while the use of narrow band imaging (NBI) has been reported to enhance the diagnostic value of white light endoscopy (WLE). The purpose of this study is to assess observer variability and diagnostic value of both modalities and investigate the possible influence of previous laryngeal surgery on the detection rates of laryngeal malignancy. METHODS: The study was based on the retrospective evaluation of 170 WLE and NBI images of laryngeal lesions by three observers in a random order. The histopathological diagnoses serve as the gold standard. RESULTS: In identifying laryngeal malignancy, the sensitivity of NBI proved to be higher than that of WLE (93.3% vs. 77.0%). NBI was also superior to WLE in terms of accuracy (96.3% vs. 92%) and diagnostic odds ratio (501.83 vs. 120.65). Both modalities had a specificity of 97.3%. The inter-observer agreement was substantial (kappa = 0.661) for WLE and almost perfect (kappa = 0.849) for NBI. Both WLE and NBI showed a high level of intra-observer agreement. The sensitivity was significantly lower in images with history of previous laryngeal surgery compared to those without. CONCLUSIONS: Flexible transnasal endoscopy has been proved to be a valuable tool in the diagnosis of laryngeal malignancy. The use of NBI can increase the sensitivity and observer reliability in that context and can also provide a diagnostic gain in cases with previous laryngeal surgery.

Non-technical skills training in the operating theatre: A meta-analysis of patient outcomes.

BACKGROUND: Non-technical skills (NTS) failures have been implicated in a large proportion of surgical errors. The objective of this meta-analysis was to investigate whether NTS training of theatre staff improves patient outcomes. METHODS: In a systematic literature search all interventional studies evaluating the effects of NTS training of theatre staff were identified. Primary outcomes included mortality, morbidity, readmission rate and length of hospital stay. Secondary outcomes included staff NTS, checklist use and technical surgical performance. Pooled odds ratios (OR) were determined for event rates and weighted mean differences (WMD) for continuous data. An inverse variance method in a random effects model was used for meta-analysis. RESULTS: A total of 1381 records were identified and nine studies were included. Meta-analysis of mortality was not carried out because only two controlled studies with different study designs were identified. No statistically significant differences were seen in complication rate (5 studies, OR 0.91 [0.73, 1.14]; p = 0.43), readmission rate (3 studies, OR 0.90 [0.63, 1.28], p = 0.56) and length of hospital stay (3 studies, WMD -0.88 days [-2.06, 0.31], p = 0.31) after NTS training. Of the secondary outcomes, an improvement of whole team NOTECHS II scores was observed in the intervention group (3 studies, WMD 6.97 [3.88, 10.06], p < 0.0001). Technical performance and checklist use were unchanged. CONCLUSIONS: This meta-analysis failed to find a statistically significant improvement of patient outcomes. These conclusions are based on a small number of heterogeneous studies. Further appropriately powered studies are likely to improve our understanding of the effects of NTS training.

Peripheral nerve atrophy together with higher cerebrospinal fluid progranulin indicate axonal damage in amyotrophic lateral sclerosis.

INTRODUCTION: We aimed to investigate whether sonographic peripheral cross-sectional nerve area (CSA) and progranulin (PGRN), a neuritic growth factor, are related to each other and whether they interact to predict clinical and paraclinical measures in amyotrophic lateral sclerosis (ALS). METHODS: We included 55 ALS patients who had forearm median and ulnar nerve CSA, cerebrospinal fluid (CSF) PGRN, and serum PGRN measures available. CSF PGRN was normalized against the CSF / serum albumin ratio (Qalb ). Using age, sex, height, and weight adjusted general linear models, we examined CSA × CSF PGRN interaction effects on various measures. RESULTS: There was a medium-effect size inverse relationship between CSA and CSF PGRN, but not between CSA and serum PGRN. Lower CSA values together with higher CSF PGRN levels were linked to smaller motor amplitudes. DISCUSSION: In ALS, the constellation of peripheral nerve atrophy together with higher CSF PGRN levels indicates pronounced axonal damage. Muscle Nerve 57: 273-278, 2018.

Protocol of the PANCALYZE trial: a multicenter, prospective study investigating the tumor biomarkers CXCR4, SMAD4, SOX9 and IFIT3 in patients with resected pancreatic adenocarcinoma to predict the pattern of recurrence of the disease.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies today with an urgent need for novel therapeutic strategies. Biomarker analysis helps to better understand tumor biology and might emerge as a tool to develop personalized therapies. The aim of the study is to investigate four promising biomarkers to predict the clinical course and particularly the pattern of tumor recurrence after surgical resection. DESIGN: Patients undergoing surgery for PDAC can be enrolled into the PANCALYZE trial. Biomarker expression of CXCR4, SMAD4, SOX9 and IFIT3 will be prospectively assessed by immunohistochemistry and verified by rt.-PCR from tumor and adjacent healthy pancreatic tissue of surgical specimen. Immunohistochemistry expression pattern of all four biomarkers will be combined into a single score. Beginning with the hospital stay clinical data from enrolled patients will be collected and followed. Different adjuvant chemotherapy protocols will be used to create subgroups. The combined biomarker expression score will be correlated with the further clinical course of the patients to test the hypothesis if CXCR4 positive, SMAD4 negative, SOX9 positive, IFIT3 positive tumors will predominantly develop metastatic spread. DISCUSSION: Pancreatic cancer is associated with different patterns of progression requiring personalized therapeutic strategies. Biomarker expression analysis might be a tool to predict the pattern of tumor recurrence and discriminate patients that develop systemic metastatic disease from those with tumors that rather develop local recurrence over time. This data might lead to personalized adjuvant treatment decisions as patients with tumors that stay localized might benefit from adjuvant local therapies like radiochemotherapy as compared to those with systemic recurrence who would benefit exclusively from chemotherapy. Moreover, the pattern of propagation might be a predefined characteristic of pancreatic cancer determined by the genetic signature of the tumor. In the future, biomarker expression analysis could be performed on tumor biopsies to develop personalized therapeutic pathways right after diagnosis of cancer. TRIAL REGISTRATION: German Clinical Trials Register, DRKS00006179 .

Risk factors for delayed gastric emptying after esophagectomy.

PURPOSE: Delayed gastric emptying (DGE) is a common functional disorder after esophagectomy with gastric tube reconstruction. Little is known about risk factors that can predict this debilitating complication. METHODS: Patients who underwent elective esophagectomy from 2008 to 2016 in a single center were retrospectively reviewed. Diagnosis of DGE was based on clinical, radiological, and endoscopic findings. Uni- and multivariate analyses were performed to identify patient-, tumor-, and procedure-related factors that increase the risk of DGE. RESULTS: One hundred eighty-two patients were included. Incidence of DGE was 39.0%. Overall, 27 (14.8%) needed an endoscopic intervention. Patients in the DGE group had a longer hospital stay (p < 0.01). No differences were found for the 30-day (p = 1.0) and hospital mortality (p = 1.0). On univariate analyses, a significant influence on DGE was demonstrated for pre-existing pulmonary comorbidity (p = 0.04), an anastomotic leak (p < 0.01), and postoperative pulmonary complications (pneumonia: p = 0.02, pleural empyema: p < 0.01, and adult respiratory distress syndrome: p = 0.03). Furthermore, there was a non-significant trend toward an increased risk for DGE for the following variable: female gender (p = 0.09) and longer operative time (p = 0.09). On multivariate analysis, only female gender (p = 0.03) and anastomotic leak (p = 0.01) were significantly associated with an increased risk for DGE. CONCLUSIONS: DGE is a frequent complication following esophagectomy that can successfully be managed with conservative or endoscopic measures. DGE did not increase mortality but was associated with increased morbidity and prolonged hospitalization. We identified risk factors that increase the incidence of DGE. However, this has to be confirmed in future studies with standardized definition of DGE.

[Reduction of post-surgical pain by Manual Medicine following tonsillectomy in adults]. / Reduktion postoperativer Schmerzen durch Manuelle Medizin bei Erwachsenen nach Tonsillektomie.

Objective Postoperative pain after tonsillectomy (TE) can usually be treated sufficiently by non-steroidal anti-inflammatory drugs (NSAIDs). In some patients, however, postoperative pain is more prominent on one side of the neck. Our clinical experience has demonstrated that these patients often show a segmental hypomobility of the upper cervical joints that can be successfully treated by manual medicine (MM). The analgetic effectiveness of this treatment was investigated in a prospective, randomized, placebocontrolled, single-blind study. Material and Methods 52 adults with exceptionally strong (visual analog scale VAS > 4) and/or unilateral pain after TE (between day 1 and 4) were included in this study. Postoperatively (TE) pain scores were immediately evaluated by VAS before (t0) and after (t1) the treatment (MM) as well as 4 hours (t2) and 1 day later (t3). Results Results show a significantly higher reduction in pain in the verum group compared to the placebo group (t1: p = 0.012, t3: p = 0.012, both Bonferroni-adjusted). The difference to t2 was not significant (p = 0.54 Conclusion This study has demonstrated effective pain reduction by manual medicine in adults with exceptionally strong and/or unilateral pain after TE and cervical hypomobolity.

Quantifying disease progression in amyotrophic lateral sclerosis using peripheral nerve sonography.

INTRODUCTION: In this study we investigated whether peripheral nerve sonography could be used as a biomarker to monitor disease progression in amyotrophic lateral sclerosis (ALS). METHODS: In 37 patients, ulnar and median nerve cross-sectional area (CSA) was determined in at least 2 ultrasound sessions; mean follow-up was 14.5 months. Linear mixed-effects models were conducted to analyze time effects on CSA. RESULTS: Ulnar nerve CSA declined significantly at a monthly rate of -0.04 mm(2) (forearm) and -0.05 mm(2) (wrist); the decrease was more pronounced when baseline CSA was greater. To detect a 50% treatment effect on ulnar nerve CSA, 332 patients would need to be entered in a hypothetical randomized, controlled clinical trial. Time had no significant impact on median nerve CSA. CONCLUSIONS: Distal ulnar nerve ultrasound may be a useful biomarker to monitor disease progression in ALS, especially as hypothetical treatment effects on CSA seem to be detectable in manageable cohort sizes. Muscle Nerve 54: 391-397, 2016.

Sciatic nerve ligation causes impairment of mitochondria associated with changes in distribution, respiration, and cardiolipin composition in related spinal cord neurons in rats.

Sciatic nerve irritation is often associated with disturbed Ca(2+) homeostasis in related neurons of the spinal cord. Since mitochondria substantially contribute to Ca(2+) homeostasis and little information is available, we studied the effects of loose sciatic nerve ligation, a chronic constriction injury (CCI), on neuronal mitochondria of the L3-L6 regions. Three groups of rats (untreated, sham operated, and ligated) were explored. For the characterization of mitochondria, specimens of the L3-L6 spinal cord regions were evaluated with respect to intracellular localization using pyruvate dehydrogenase immunohistochemistry and Mitotracker Red, and the ATP producing machinery by LC-MS/MS technique for the analysis of cardiolipin and high-resolution respirometry for the measurement of oxygen consumption. Therefore, the phospholipid cardiolipin supports electron transfer within the respiratory chain as part of mitochondrial respiration and is of high impact on the physical properties of the mitochondrial membrane system. Histological analysis of spinal cord motor neurons revealed clustering of mitochondria in ipsilateral samples from ligated animals 14 days after the insult. This phenomenon was similarly evident in the respective contralateral side. The intensity of MT-Red staining was enhanced exclusively at the ipsilateral side, indicating increased mitochondrial activity. CCI of the sciatic nerve caused massive changes in the composition of cardiolipin reflecting mitochondrial impairment in the early phase followed by regeneration processes as late response. Sciatic nerve CCI caused decrease in the capacity of mitochondrial ATP production that recovered within 14 days after treatment. In conclusion, we provide evidence that clustering of mitochondria, already verified for the spinal cord sensory neurons after CCI, also occurs in the respective motor neurons. Further we have demonstrated transient impairment of the capacity of mitochondrial ATP production in tissue samples. Stress-dependent changes in cardiolipin composition are sensitive markers and mediators of the response process including impairment and regeneration.

Sensory perceptions of individuals exposed to the static field of a 7T MRI: A controlled blinded study.

PURPOSE: To determine the subjective experience of subjects undergoing 7T magnetic resonance imaging (MRI) compared to a mock scanner with no magnetic field. METHODS AND MATERIALS: In all, 44 healthy subjects were exposed to both the B0 field of a 7T whole-body MRI and a realistic mock scanner with no magnetic field. Subjects were blinded to the actual field strength and no scanning was performed. After exposure, subjects rated their experience of potential sensory perceptions. RESULTS: The most frequently observed side effect was vertigo while entering the gantry, which was reported by 38.6% (n = 17). Other frequent side effects were the appearance of phosphenes (18.2%, n = 8), thermal heat sensation (15.9%), unsteady gait after exposure (13.6%, n = 6), and dizziness (13.6%). All side effects were reported significantly more often after 7T exposure. Nine subjects (20.5%) did not report any sensory perceptions at all, ie, neither in the 7T scanner nor in the mock scanner. CONCLUSION: Light, acute, and transient sensory perceptions can occur in subjects undergoing ultrahighfield MRI, of which vertigo seems to be the most frequently reported. Possible psychological effects might contribute to the emergence of such sensory perceptions, as some subjects also reported them to appear in a realistic mock scanner with no magnetic field.