Study protocol of a cluster-randomised controlled trial assessing a multimodal machine-based exercise training programme in senior care facilities over 6 months - the bestform study (best function of range of motion).

BACKGROUND: Physical functioning is a crucial factor for independence and quality of life in old age. The aim of the "bestform-Best function of range of motion" trial is to investigate the effects of a 6 months multimodal machine-based strength, coordination and endurance training on physical function, risk of falls and health parameters in older adults. METHODS: Bestform is a cluster-randomised trial including older adults ≥ 65 years living in senior care facilities in Southern Germany. Senior care facilities are randomly allocated to the control group with usual care (n ≥ 10 care facilities) and to the intervention group (n ≥ 10 care facilities), overall including ≥ 400 seniors. Residents belonging to the intervention group are offered a supervised machine-based exercise training programme twice weekly over 45-60 min over six months in small groups, while those in the usual care facilities will not receive active intervention. The primary outcome is the change in Short Physical Performance Battery over six months between groups. Secondary outcomes are change in risk of falling, fear of falling, number of falls and fall-related injuries, physical exercise capacity, handgrip strength, body composition, cardiac function, blood parameters, quality of life, risk of sarcopenia, activities of daily living, and cognition over three and six months. DISCUSSION: The bestform study investigates the change in physical function between seniors performing exercise intervention versus usual care over six months. The results of the study will contribute to the development of effective physical activity concepts in senior care facilities. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04207307. Registered December 2019.

Influence of antiretroviral therapy and cardiovascular disease on the immature platelet fraction in patients living with HIV.

Cardiovascular disease is an important contributor to morbidity and mortality in people living with HIV . The immature platelet fraction (IPF) is increased in HIV-negative patients with cardiovascular disease and evidence suggests that an enlarged IPF is associated with adverse cardiovascular events. In this multi-center observational study, we aimed to investigate how the IPF in people living with HIV is influenced by antiretroviral therapy and cardiovascular disease. Subjects without cardiovascular disease that received antiretroviral therapy showed a smaller IPF accompanied by lower D-dimer and C-reactive protein (CRP) levels compared to therapy-naïve subjects (mean IPF: 2.9% vs. 3.9%, p = .016; median D-dimer: 252 µg/L vs. 623 µg/L, p < .001; median CRP: 0.2 mg/dL vs. 0.5 mg/dL, p = .004). No significant differences for the IPF, D-dimer or CRP were found between subjects on antiretroviral therapy with documented cardiovascular disease and therapy-naïve subjects. In conclusion, we observed a reduction in the IPF among subjects on therapy only in the absence of cardiovascular disease. In contrast, subjects receiving therapy that had documented cardiovascular disease showed an IPF comparable to therapy-naïve subjects. Future studies are needed to investigate if an enlarged IPF may serve as a biomarker in predicting adverse cardiovascular events in people living with HIV.

Fetal heart rate variability responsiveness to maternal stress, non-invasively detected from maternal transabdominal ECG.

PURPOSE: Prenatal stress (PS) during pregnancy affects in utero- and postnatal child brain-development. Key systems affected are the hypothalamic-pituitary-adrenal axis and the autonomic nervous system (ANS). Maternal- and fetal ANS activity can be gauged non-invasively from transabdominal electrocardiogram (taECG). We propose a novel approach to assess couplings between maternal (mHR) and fetal heart rate (fHR) as a new biomarker for PS based on bivariate phase-rectified signal averaging (BPRSA). We hypothesized that PS exerts lasting impact on fHR. METHODS: Prospective case-control study matched for maternal age, parity, and gestational age during the third trimester using the Cohen Perceived Stress Scale (PSS-10) questionnaire with PSS-10 over or equal 19 classified as stress group (SG). Women with PSS-10 < 19 served as control group (CG). Fetal electrocardiograms were recorded by a taECG. Coupling between mHR and fHR was analyzed by BPRSA resulting in fetal stress index (FSI). Maternal hair cortisol, a memory of chronic stress exposure for 2-3 months, was measured at birth. RESULTS: 538/1500 pregnant women returned the questionnaire, 55/538 (10.2%) mother-child pairs formed SG and were matched with 55/449 (12.2%) consecutive patients as CG. Maternal hair cortisol was 86.6 (48.0-169.2) versus 53.0 (34.4-105.9) pg/mg (p = 0.029). At 36 + 5 weeks, FSI was significantly higher in fetuses of stressed mothers when compared to controls [0.43 (0.18-0.85) versus 0.00 (- 0.49-0.18), p < 0.001]. CONCLUSION: Prenatal maternal stress affects the coupling between maternal and fetal heart rate detectable non-invasively a month prior to birth. Lasting effects on neurodevelopment of affected offspring should be studied. TRIAL REGISTRATION: Clinical trial registration: NCT03389178.

T2-relaxation time of cartilage repair tissue is associated with bone remodeling after spongiosa-augmented matrix-associated autologous chondrocyte implantation.

OBJECTIVE: To investigate whether T2 relaxation time measurements of cartilage repair tissue and structural changes of the knee joint are associated with subchondral bone architecture after spongiosa-augmented matrix-associated autologous chondrocyte implantation (MACI). DESIGN: Both knees of 25 patients (25.5 ± 7.8y; 10 women) were examined preoperatively and 2.7 years after unilateral spongiosa-augmented MACI with 3T magnetic resonance (MR) imaging. Cartilage composition was assessed using T2 relaxation time measurements, subchondral trabecular bone microstructure was quantified using a 3D phase-cycled balanced steady state free-precision sequence. Structural knee joint changes were assessed using the modified Whole-Organ Magnetic Resonance Imaging Score (WORMS). The Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score was used for the postoperative description of the area that underwent MACI. Correlations were assessed using Spearman's rank correlation coefficients. RESULTS: Hypertrophy of the cartilage repair tissue was found in 2 of 25 patients, both after a MACI procedure at the patella, 21 patients showed congruent filling. In subchondral bone of the cartilage repair compartment, apparent trabecular thickness was significantly higher in compartments with elevated cartilage T2 (n = 17; 0.37 ± 0.05 mm) compared to those showing no difference in cartilage T2 compared to the same compartment in the contralateral knee (n = 8; 0.27 ± 0.05 mm; P = 0.042). Significant correlations were found between the overall progression of WORMS and the ipsilateral vs contralateral ratio of average trabecular thickness (r = 0.48, P = 0.031) and bone fraction (r = 0.57, P = 0.007). CONCLUSIONS: After spongiosa-augmented MACI, T2 values of cartilage repair tissue and structural knee joint changes correlated with the quality of the underlying trabecular bone.

Three-dimensional fat-saturated T1-weighted Cartesian volumetric interpolated breath-hold examination (VIBE) for the diagnosis of aortitis in patients with suspected large vessel vasculitis: a comparative study with 18F-FDG PET applying fully integrated PET/MRI.

AIM: To evaluate the feasibility of T1-weighted (T1W) three-dimensional (3D) fat saturated Cartesian volumetric interpolated breath-hold examination (VIBE) magnetic resonance imaging (MRI) sequence for the diagnosis of aortitis in patients with suspected large vessel vasculitis (LVV) applying fully integrated 2-[18F]-fluoro-2-deoxy-d-glucose (18F-FDG) positron-emission tomography (PET)/MRI. MATERIAL AND METHODS: Fourteen patients with aortitis and 14 patients with a negative study for aortitis using 18F-FDG PET as the standard of reference for the evaluation of inflammatory aortic involvement were included retrospectively. All patients were imaged at 3 T using T1W VIBE pre- and post-contrast. Four aortic segments were evaluated for image quality (IQ), diagnostic confidence (DC), and the degree of inflammatory activity (IA) using a Likert scale. Binomial and generalised estimating equation model tests were used to assess the diagnostic performance of T1W VIBE. Cohen's k was applied to test for interobserver reproducibility with respect to IA. Spearman's rank correlation coefficient was calculated to examine correlations between IQ, DC, IA, and PET results. RESULTS: On a patient- and segment-based analysis, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 85.7% and 59.8%, 100% and 100%, 100% and 100%, 87.5% and 68%, and 92.9% and 82.1%, respectively. IQ and DC were acceptable to good in all examinations and substantial interobserver agreement was observed for IA (Cohen's k = 0.69). IQ and DC as well as IA and 18F-FDG vessel wall uptake were significantly correlated (r=0.763 and 0.679, respectively; p<0.0001). CONCLUSION: T1W 3D fat saturated VIBE MRI allows diagnosis of aortitis and may aid in the management of patients with suspected LVV.

Influence of gestational diabetes on fetal autonomic nervous system: a study using phase-rectified signal-averaging analysis.

OBJECTIVES: Maternal gestational diabetes mellitus (GDM) is known to influence fetal physiology. Phase-rectified signal averaging (PRSA) is an innovative signal-processing technique that can be used to investigate fetal heart signals. The PRSA-calculated variables average acceleration capacity (AAC) and average deceleration capacity (ADC) are established indices of autonomic nervous system (ANS) function. The aim of this study was to evaluate the influence of GDM on the fetal cardiovascular and ANS function in human pregnancy using PRSA. METHODS: This was a prospective clinical case-control study of 58 mothers with diagnosed GDM and 58 gestational-age matched healthy controls in the third trimester of pregnancy. Fetal cardiotocography (CTG) recordings were performed in all cases at entry to the study, and a follow-up recording was performed in 19 GDM cases close to delivery. The AAC and ADC indices were calculated by the PRSA method and fetal heart rate short-term variation (STV) by CTG software according to Dawes-Redman criteria. RESULTS: Mean gestational age of both groups at study entry was 35.7 weeks. There was a significant difference in mean AAC (1.97 ± 0.33 bpm vs 2.42 ± 0.57 bpm; P < 0.001) and ADC (1.94 ± 0.32 bpm vs 2.28 ± 0.46 bpm; P < 0.001) between controls and fetuses of diabetic mothers. This difference could not be demonstrated using standard computerized fetal CTG analysis of STV (controls, 10.8 ± 3.0 ms vs GDM group, 11.3 ± 2.5 ms; P = 0.32). Longitudinal fetal heart rate measurements in a subgroup of women with diabetes were not significantly different from those at study entry. CONCLUSIONS: Our findings show increased ANS activity in fetuses of diabetic mothers in late gestation. Analysis of human fetal cardiovascular and ANS function by PRSA may offer improved surveillance over conventional techniques linking GDM pregnancy to future cardiovascular dysfunction in the offspring. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Trends in Patient Safety of Intact Abdominal Aortic Aneurysm Repair: German Registry Data on 36,594 Procedures.

OBJECTIVE/BACKGROUND: The study aim was to determine whether patient safety for non-ruptured abdominal aortic aneurysm (nrAAA) repair has changed between 1999 and 2010 in a large German cohort. METHODS: The data source was the prospective quality assurance registry of the German Vascular Society from 1999 to 2010. Patient characteristics, surgical techniques (open aortic repair [OAR], endovascular aortic repair [EVAR]), procedural time and outcomes, including the length of hospital stay (LOS), were analysed using the Cochran-Armitage test for binary parameters and Spearman's correlation coefficient for quantitative parameters. RESULTS: A total of 36,594 operations (23,037 OAR, 13,557 EVAR) for infrarenal nrAAA in 201 hospitals in Germany were investigated. Patients' mean age increased from 69.6 to 72.0 years (p < .001). The rate of patients with American Society of Anesthesiologists scores of 3 or 4 increased (p < .001). Use of EVAR increased (1999: 16.7%; 2010: 62.7%; p < .001), and since 2009, EVAR has been more frequently used than OAR. The overall in hospital mortality decreased from 3.1% in 1999 to 2.3% in 2010 (p < .001). There were no temporal trends for mortality rates for EVAR (p = .233) or OAR (p = .281) when considered separately. Cardiac (1999: 8.1%; 2010: 5.1%; p < .001) and pulmonary (1999: 7.8%; 2010: 4.8%; p < .001) complications decreased. The rate of post-operative renal failure increased (1999: 3.6%; 2010 4.1%; p = .017), without increasing the rate of patients needing dialysis (1999: 1.7%; 2010: 1.7%; p = .171). The median LOS decreased from 17 days in 1999 to 10 days in 2010 (p < .001). CONCLUSION: This study shows significantly improved post-procedural in hospital outcomes and decreased use of resources for nrAAA repair. This trend can probably be attributed to the implementation of EVAR as a standard technique, but some trends could also possibly be explained by a change in the remuneration system. The main limitation of the registry is the lack of internal and external validation. However, in hospital patient safety for AAA repair seems to have improved significantly in the participating hospitals.

Esophageal bougination: a novel ex vivo endoscopic training model correlated with clinical data.

BACKGROUND: Esophageal bougination is a worldwide standard endoscopic procedure. Clinical methods and recommendations are based on clinical experiences only. Mechanical properties have never been described. Aim of the study was to establish a realistic ex vivo training model. Therefore, detailed assessment of relevant mechanical features of esophageal bougination should be evaluated ex vivo and in patient setting and correlated against. PATIENTS AND METHODS: A three-step concept was used to evaluate mechanical properties at stenosis level. First, insertion forces were evaluated in an ex vivo linear single stenosis model during steady mechanical insertion. Second, adding friction and properties of the pharynx and upper esophagus, the model was integrated in an artificial endoscopic training model (ELITE training model). Third, in vivo measurements were taken to correlate ex vivo data with parameters of a realistic patient setting. RESULTS: With the presented setup, we were able to assess insertion force and pressure levels in an artificial stricture using different sizes of commercially available standard bougies. In all models, there was a relevant increase in insertion force with higher stricture pressure levels. Insertion force levels in the ELITE model show higher levels compared to the linear stenosis model. Having regard to the maximum forces in patients, there is also a constant increase in mean insertion force according to higher bougie sizes, but lower forces were measured as in the ELITE model. DISCUSSION: The applied models are suitable to appraise mechanical properties of esophageal bougination in an ex vivo model and patient setting. Forces could be constituted reliable, significant increase was documented according to stenosis level and results were comparable to patient data. This was comparable to patient data. Further clinical evaluation in different kinds of stenosis is necessary.

The prognostic effect of tumour-infiltrating lymphocytic subpopulations in bladder cancer.

BACKGROUND: Intratumoural lymphocytic infiltration is strongly associated with the outcome of many human epithelial cancers. The current paper investigated whether subpopulations of tumour-infiltrating T lymphocytes are associated with certain clinicopathological parameters and the prognosis of patients with invasive bladder cancer (BCa). PATIENTS AND METHODS: The infiltration densities of the adaptive immune markers CD3 (the whole T cell population), FOXP3 (regulatory T cells; Tregs), CD8 (T effector cells) and CD45R0 (T effector memory cells) were analysed by immunohistochemistry and image analysis with tissue microarrays of tumour tissues from 149 patients with invasive BCa treated with radical cystectomy. The findings were correlated with certain clinicopathological parameters. RESULTS: Higher FOXP3/CD3 [OS: p = 0.016, HR 1.29, 95% confidence intervals (95% CIs 1.05-1.59)] and FOXP3/CD8 (OS: p = 0.013, HR 1.32, 95% CIs 1.06-1.65) ratios were significantly associated with briefer overall survival and time to cancer-specific death; the latter ratio represented an independent prognostic factor according to a multivariate analysis adjusted for pathological T and N stages (HR 1.32, 95% CIs 1.05-1.67, p = 0.018). The infiltration densities of individual markers (CD3, CD8, FOXP3 and CD45R0) were not significantly associated with clinicopathological parameters or survival; however, a trend towards a better outcome was observed for higher log-transformed CD8 (p = 0.070, HR 0.80, 95% CIs 0.63-1.02) and CD3 (p = 0.113, HR 0.84, 95% CIs 0.68-1.04) infiltration values. CONCLUSIONS: A high fraction of Tregs amongst CD3- and CD8-positive lymphocytes indicated a poor prognosis, thereby emphasising the important role that Tregs play in the suppression of the anti-tumour immune response. No single lymphocytic marker was significantly correlated with clinical outcomes, but high CD3 and CD8 infiltration showed trends towards better prognosis.

Measurements After Image Post-processing Are More Precise in the Morphometric Assessment of Thoracic Aortic Aneurysms: An Intermodal and Intra-observer Evaluation.

OBJECTIVES: Precise pre-procedural anatomical analysis of aneurysmal anatomy is essential for successful thoracic endovascular aortic repair (TEVAR). Since surgeons and radiologists have to perform multiple measurements in the same patient, high intra-observer reliability of any imaging method is mandatory. Commercially available three dimensional (3D) post-processing techniques are expected to be superior to conventional two dimensional multiplanar reconstructions (MPRs) derived from computed tomography angiograms (CTAs). However, few data exist to support this view. This study aims to evaluate the intermodal and intra-observer differences using 3D software (3surgery) in descending thoracic aortic aneurysms (dTAAs). METHODS: Pre-operative CTAs (performed between 2004 and 2010) of 30 dTAAs (mean maximum diameter 61.4 ± 13 mm) were assessed by three independent investigators with different experience in the measurement of aortic pathologies. Intra-observer reliability and intermodal differences (3D vs. 2D) were investigated using pre-specified measurement points (distances of total length, maximum diameter, proximal and distal landing zones). Statistical analyses were performed using the Bland-Altman method and a mixed regression model. RESULTS: Intermodal comparison showed that 2D measurements significantly underestimate the measured distances (maximum diameter 3.7 mm [95% CI -5.3 to -2.1] and landing zone maximum 1.4 mm [95% CI -2.0 to -0.2] shorter with 2D, p < .05). In almost all 3D measurements, all investigators showed lower variability comparing the intra-observer differences, most notably in the measuring point total length (reduction of the SD up to 7.9 mm). CONCLUSIONS: These data show that both techniques led to significant measurement disparity. This occurs especially at the point of indication (maximum diameter) and the total length of the aneurysm (important for correct stent graft selection). But overall the variability is reduced with the 3D technique, which also tends to measure greater distances. The use of post-processing software therefore leads to more precise device selection for TEVAR in TAA.

[Indication-Related Effectivity of Cervical Occlusion Techniques in Women with Threatening Preterm Birth]. / Indikationsbezogene Effektivität von Verschlussoperationen am Muttermund.

The aim of this study was to identify which operation technique [total cervical occlusion (TMV), cerclage (C) or combination of both (TMV+C)] would lead to the greatest pregnancy prolongation in 3 different collectives of patients at risk (history of preterm birth, cervical insufficiency, prolapsing membranes). In this retrospective data collection, 200 cervical occlusions performed between 1997 and 2010 were analysed. In patients with a history of preterm birth/stillbirth (n=80) a prophylactic TMV increased the lifebirth rate from 35% without TMV to 95% with TMV (p<0.001). The risk diminuation after TMV was - 60% for stillbirth (p<0.001) and - 30% for preterm birth (p=0.01). In this subcollective the TMV seemed to be more effective in pregnancy prolongation (days) than C (139 vs. 113 days), however the combination of both (C+TMV) did not add much benefit (142 days). In patients with cervical insuffiency (n=86) the pregnancy could be prolonged by 82 (C), 79 (TMV) und 109 days (C+TMV) (p=0.003-0.017) and in patients with membrane prolaps (n=34) by 63 (C), 61 (TMV) und 76 (C+TMV) days. According to present data, the combination of cerclage and TMV has the highest benefit on pregnancy prolongation. This analysis should provide a basis for randomised controlled studies on this topic.

Association of leptin and insulin with childhood obesity and retinal vessel diameters.

OBJECTIVE: Childhood obesity is associated with an impaired retinal microcirculation. The aim of the study was to investigate the association between specific obesity-related biomarkers, physical fitness and retinal vessel diameters in school children. DESIGN AND SUBJECTS: We studied 381 children aged 10-11 years (body mass index (BMI): 19.3±3.7 kg m(-2)) in a school-based setting. MEASUREMENTS: Anthropometric measurements and blood sampling were conducted using standard protocols for children. The serum biomarkers leptin, adiponectin, insulin as well as interleukin-6 (IL-6) were analyzed. Physical fitness was determined by a six-item-test battery and physical activity by use of a questionnaire. Central retinal arteriolar equivalent (CRAE), central retinal venular equivalent (CRVE) and the arteriolar-to-venular diameter ratio (AVR) were assessed with a non-mydriatic vessel analyzer (SVA-T) using a computer-based program. RESULTS: Compared with normal weight children (n=254), obese children (n=39) showed higher leptin (P<0.001), higher insulin (P<0.001), higher IL-6 (P<0.001) and lower adiponectin levels (P=0.013). Obese children demonstrated wider CRVE (P=0.041) and lower AVR (P<0.001). Higher leptin levels were associated with wider CRVE (P=0.032) and lower AVR (P=0.010), that was BMI dependent. Insulin levels were associated with arteriolar (P=0.045) and venular dilatation (P=0.034) after adjustment for BMI. No significant associations between adiponectin levels, IL-6 levels, physical fitness or physical activity and retinal vessel diameter were observed. Lower leptin levels were independently correlated with higher physical fitness (r=-0.33; P<0.001). CONCLUSION: Leptin and insulin levels are associated with changes of the retinal microcirculation. Especially insulin seems to be a good target marker for the cardiometabolic risk assessment in children since elevated insulin levels are independently associated with microvascular end-organ alterations at an early stage. Lifestyle intervention studies are warranted to examine whether improvement of physical fitness or weight reduction can affect cardiometabolic risk markers and reverse alterations of the retinal microcirculation.

Cisplatin- vs. oxaliplatin-based radiosensitizing chemotherapy for squamous cell carcinoma of the esophagus: a comparison of two preoperative radiochemotherapy regimens.

PURPOSE: To compare the outcomes of two neoadjuvant radiochemotherapy (N-RCT) regimens for squamous cell carcinoma of the esophagus (ESCC). METHODS: The standard N-RCT regimen for ESCC at our institution between 2002 and 2011 was a total dose of 45 Gy (1.8-Gy fractions) with concomitant cisplatin (20 mg/m(2), days 1-5 and 29-33) and 5-fluorouracil (5-FU; 225 mg/m(2), 24 h continuous infusion on days 1-33). During the same period, a phase I/II study comparing the standard ESCC N-RCT protocol with a regimen identical except for the replacement of cisplatin with weekly oxaliplatin (40-50 mg/m(2)) was performed at our center. The standard regimen was used to treat 40 patients; 37 received the oxaliplatin regimen. All patients subsequently underwent radical resection with reconstruction according to tumor location and two-field lymph node dissection. RESULTS: Median follow-up time from the start of N-RCT was 74 months (range 3-116 months). The two patient groups were comparable in terms of demographic and baseline tumor characteristics. R0 resection was achieved in 37/39 patients (95 %) in the cisplatin-based N-RCT group, compared to 24/37 (65 %) in the oxaliplatin-based group (p = 0.002). A pathological complete response (pCR) was seen in the resection specimens from 18/39 patients (46 %) in the cisplatin-based N-RCT group and in 8/37 (22 %) oxaliplatin-group patients. In the cisplatin group, 2- and 5-year overall survival (OS) rates were 67 ± 8 % and 60 ± 8 %, respectively (median OS 103 months), compared to 38 ± 8 % and 32 ± 8 %, respectively, for the oxaliplatin group (median OS 17 months; hazard ratio, HR 0.452; 95 % confidence interval, CI 0.244-0.839; p = 0.012). CONCLUSION: Oxaliplatin-based N-RCT resulted in poorer outcomes in ESCC patients and should not routinely replace cisplatin-based N-RCT.

The founding of Mauritian endemic coffee trees by a synchronous long-distance dispersal event.

The stochastic process of long-distance dispersal is the exclusive means by which plants colonize oceanic islands. Baker's rule posits that self-incompatible plant lineages are unlikely to successfully colonize oceanic islands because they must achieve a coordinated long-distance dispersal of sufficiently numerous individuals to establish an outcrossing founder population. Here, we show for the first time that Mauritian Coffea species are self-incompatible and thus represent an exception to Baker's rule. The genus Coffea (Rubiaceae) is composed of approximately 124 species with a paleotropical distribution. Phylogenetic evidence strongly supports a single colonization of the oceanic island of Mauritius from either Madagascar or Africa. We employ Bayesian divergence time analyses to show that the colonization of Mauritius was not a recent event. We genotype S-RNase alleles from Mauritian endemic Coffea, and using S-allele gene genealogies, we show that the Mauritian allelic diversity is confined to just seven deeply divergent Coffea S-RNase allelic lineages. Based on these data, we developed an individual-based model and performed a simulation study to estimate the most likely number of founding individuals involved in the colonization of Mauritius. Our simulations show that to explain the observed S-RNase allelic diversity, the founding population was likely composed of fewer than 31 seeds that were likely synchronously dispersed from an ancestral mainland species.

Impact of pathologic complete response on disease-free survival in patients with esophagogastric adenocarcinoma receiving preoperative docetaxel-based chemotherapy.

BACKGROUND: The aim of this study was to evaluate the impact of pathologic complete response (pCR) on outcome in patients with gastric or esophagogastric junction (EGJ) adenocarcinoma after neoadjuvant docetaxel/platin/fluoropyrimidine-based chemotherapy. PATIENTS AND METHODS: Patients received at least one cycle of chemotherapy for potentially operable disease. Pretreatment clinicopathologic factors and pCR were investigated. Disease-free survival (DFS), overall survival (OS) and tumor-related death were correlated with pCR. RESULTS: One hundred twenty patients were included in this analysis. Eighteen patients (15%) achieved a pCR. Tumor localization in the EGJ was identified as the only significant predictor of pCR (P = 0.019). Median follow-up was 41.1 months. Median DFS and OS for all patients were 24.1 and 48.6 months, respectively. Median DFS for patients with a pCR was not reached versus 22.1 months non-pCR patients (hazard ratio, HR 0.38; 3-year DFS: 71.8% and 37.7%, respectively, P = 0.018). While OS was not significantly different, the risk for tumor-related death was significantly lower for pCR patients compared with non-pCR patients (3-year cumulative incidences of 6.4% and 45.4%, respectively, P = 0.009). CONCLUSION: A pCR following preoperative docetaxel/platin/fluoropyrimidine indicates favorable outcome in patients with gastric or EGJ adenocarcinoma. Tumor location in the EGJ is associated with a higher pCR rate.

Radiotherapy with or without chemotherapy in the treatment of anal cancer: 20-year experience from a single institute.

PURPOSE: To report the efficacy and toxicity of radio(chemo)therapy (RCT) in the management of squamous cell anal carcinoma (SQ-AC) and to evaluate the prognostic factors influencing the outcomes. PATIENTS AND METHODS: A consecutive cohort of 138 patients with cT1-4, cN0-3, cM0 SQ-AC were treated with RCT between 1988 and 2011 at our department. Median follow-up time for surviving patients from the start of RCT was 98 months (range, 1-236 months). Patients were treated with a median radiation dose of 56 Gy (range, 4-61 Gy). Concurrent chemotherapy was administered to 119 patients (86%). RESULTS: The survival rates at 2, 5, and 10 years were 88 ± 3, 82 ± 4, and 59 ± 6%, respectively, with a median overall survival (OS) of 167 months. The cumulative incidence for local recurrence at 2 and 5 years was 8 ± 2 and 11 ± 3%, respectively. The median disease-free survival (DFS) and colostomy-free survival (CFS) times were 132 and 135 months, respectively. In 19 patients (14%), a distant metastasis was diagnosed after a median time of 19 months. In the multivariate analysis, UICC (International Union Against Cancer) stage I-II, female gender, Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, and good/moderate histologic differentiation (G1-2) were significantly associated with a better OS, DFS, and CFS. Conformal radiotherapy planning techniques were significantly associated with a lower cumulative incidence of local recurrence (11 ± 3% vs. 38 ± 19% at 5 years, p = 0.006). A higher radiation dose beyond 54 Gy was not associated with an improvement in outcome, neither for smaller-(T1/T2) nor for larger tumors (T3/T4). CONCLUSION: RCT leads to excellent outcomes-especially in patients with stage I/II and G1/G2 tumors-with acceptable toxicity. The probable advantages of high-dose radiotherapy should be considered carefully against the risk of a higher rate of toxicity. Future studies are needed to investigate the role of a more intensified (systemic) treatment for patients with unfavorable prognostic factors such as T3/T4, N+, and/or poor cell differentiation.

Positron-emission tomography CT to identify local recurrence in stage I lung cancer patients 1 year after stereotactic body radiation therapy.

PURPOSE: To evaluate the diagnostic value of positron-emission tomography/computed tomography (PET/CT) in stage I lung cancer patients treated with stereotactic body radiation therapy (SBRT), who have suspicious or unclear local recurrence findings in CT 1 year after treatment. PATIENTS AND METHODS: A group of 29 patients with unclear or suspicious CT findings 1 year after SBRT were examined with PET/CT. The ability of standard uptake values (SUVmax, SUVmean and posttherapeutic reduction in SUV) to detect local failure and identify patients at a high risk of disease-specific death was evaluated using logrank statistics. Histology and clinical follow-up were the gold standards for local recurrence. RESULTS: SUVmean greater than 3.44 (p = 0.001); SUVmax greater than 5.48 (p = 0.009) or a relative reduction in SUVmean or SUVmax of less than 43 (p = 0.030) or 52 % (p = 0.025), respectively, was indicative of local recurrence. These parameters also correlated with an increased risk of disease-specific death: SUVmean greater than 2.81 (p = 0.023); SUVmax greater than 3.45 (p = 0.007) or a relative reduction in SUVmean or SUVmax of less than 32 (p = 0.015) or 52 % (p = 0.013), respectively, was indicative of an increased risk of disease-specific death. CONCLUSION: PET/CT performed 1 year after SBRT can reliably identify local recurrence and therefore help to clarify unclear CT findings. As posttherapeutic glucose metabolism also correlates with disease-specific survival, PET/CT may help to stratify lung cancer patients for additional treatment 1 year after SBRT.

Clinical manifestations and treatment options in patients with cirrhosis and diabetes mellitus.

BACKGROUND: Diabetes is frequently diagnosed in patients with cirrhosis and represents an important risk factor for morbidity and mortality. Pharmacological therapy is limited due to hepatotoxicity and the risk of hypoglycemia. Investigations on medical practice in this patient population, frequency of diabetes-associated complications and the impact of quality of metabolic control are rare. AIMS AND METHODS: A retrospective analysis was performed to compare the effects of hypoglycemic treatment, the achieved glycemic control under therapy, the prevalence of typical cirrhosis-related or microangiopathic complications, and cardiovascular comorbidities between a group of diabetic patients with cirrhosis (n = 87) and a nondiabetic cirrhotic population (n = 198). RESULTS: The prevalence of diabetes in our cohort was 30.5%. Of all diabetic patients, 39.1% received therapy which might potentially result in serious side effects in patients with end-stage liver disease. The rate of ongoing alcohol abuse (28.7%) and noncompliance under medication (41.4%) was high. Only 28.7% of all diabetic subjects showed satisfactory (as defined by HbA1c ≤ 6.5%) glycemic control under therapy. Patients achieving satisfactory control experienced a lower rate of certain cirrhosis-related complications such as hepatic encephalopathy (HE) and hepatocellular carcinoma (HCC), arterial hypertension, and hypercholesterolemia. HE was significantly more frequent in diabetic than nondiabetic cirrhotic patients.

Effects of a physical education program on physical activity, fitness, and health in children: the JuvenTUM project.

The purpose of the study was to investigate the effects of a school-based prevention program on physical activity, fitness, and obesity. We performed a prospective study in eight Bavarian primary schools (n = 724 children, 8.4 ± 0.7 years) randomized one to one to either an intervention school (IS, n = 427) or a control school (CS, n = 297). Children in IS attended 10 health-related lessons at school over a period of 1 year. Parents and teachers attended two and three educational health-related lessons, respectively, and also received 10 newsletters on health issues. Daily physical activity (≥ 60 min/day), physical fitness (six-item test battery), and anthropometric data were obtained at baseline and after 1 year. Physical activity and physical fitness increased in IS, but it failed to reach significant intervention effects. Nevertheless, a reduction in waist circumference was observed for all children [mean change 1.7 cm; 95% confidence interval (CI) 1.2-2.3; P < 0.001). This effect was more pronounced in overweight children (> 90th percentile, n = 99, mean change 3.2 cm; 95% CI 1.5-4.8; P < 0.001). This easily administered preventative program involving children, parents, and teachers revealed that a generalized approach increasing physical activity will even be favorable in a subgroup of obese children.

Radio(chemo)therapy in the management of squamous cell carcinoma of cervical lymph nodes from an unknown primary site. A retrospective analysis.

PURPOSE: The goal was to retrospectively review the outcome of patients with cervical lymph node metastases of squamuos cell carcinoma of unknown primary site (CUP) treated with radio(chemo)therapy. PATIENTS AND METHODS: A total of 65 patients with CUP N1-3, M0, treated between 1988 and 2009 were evaluated: 61 patients underwent surgical resection followed by postoperative radio(chemo)therapy, 4 patients received definitive radiochemotherapy. Radiotherapy of bilateral neck nodes + the parapharyngeal region (COMP-RT) was performed in 48 patients (80%) and a unilateral radiotherapy of lymph nodes (UL-RT) in 17 patients (20%). RESULTS: After a median follow-up time of 64 months (range 3-219 months), the estimated 2- and 5-year overall survival (OS) rates were 71 ± 6% and 48 ± 7%, respectively. The recurrent free survival (RFS) rate at 2- and 5-years was 58 ± 6% and 48% ± 7%, respectively. Extracapsular spread, resection status (R0 vs. R1/R2), neck lymph node level (I-III vs. IV-V), and Karnofsky index (60-70 vs. 80-100) were significant prognostic factors for OS and RFS in the univariate analysis. Lower nodal stage (N1/N2a vs. N2b/N2c/N3) was significantly associated with a better OS. Resection status and involvement of lymph node level IV significantly affected the OS and RFS in the multivariate analysis. COMP-RT or concurrent chemotherapy was not associated with a better OS or RFS. CONCLUSION: An advantage of comprehensive radiotherapy or radiochemotherapy compared with unilateral radiotherapy of lymph nodes was not observed.