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Objective: Given the lack of maintenance interventions for eating disorders, a program delivered via the short message service (SMS) and text messaging was developed to support patients after their discharge from inpatient treatment. Method: The efficacy of the intervention was studied in a randomized controlled trial. Additionally, its impact on the utilization of outpatient treatment during follow-up was investigated. One hundred sixty-five female patients with bulimia nervosa or a related eating disorder not otherwise specified were randomly assigned to a control group (treatment as usual; TAU) or an intervention group (SMS-based maintenance intervention; SMS). After hospital discharge, participants in the intervention group submitted a weekly symptom report via text message for 16 weeks and received tailored feedback. Primary outcome was the rate of partial remission 8 months after discharge from inpatient treatment. Results: The difference in remission rates reached significance in the intent-to-treat analyses (SMS = 51.2%; TAU = 36.1%), X[superscript 2](1) = 3.81, p = 0.05, and approached significance in the completer analysis (SMS = 59.2%; TAU = 43.5%), X[superscript 2](1) = 3.44, p = 0.06. There were no differences in the utilization of outpatient treatment. Remission rates between the intervention and control groups were not significantly different among patients who used outpatient treatment (63.2% vs. 55.6%), X[superscript 2](1) = 0.44, p = 0.51. A significant difference was found in those who did not utilize such treatment (54.5% vs. 30.3%), X[superscript 2](1) = 3.97, p = 0.046. Conclusion: The aftercare intervention was efficacious in enhancing treatment outcome after discharge from inpatient treatment. (Contains 3 figures and 2 tables.)

Aims The role of right ventricular function in patients undergoing transcatheter tricuspid valve repair (TTVR) is poorly understood. This study investigated the association of right ventricular ejection fraction (RVEF) assessed by cardiac computed tomography (CCT) with clinical outcomes in patients undergoing TTVR. Methods and results We retrospectively assessed three-dimensional (3D) RVEF by using pre-procedural CCT images in patients undergoing TTVR. RV dysfunction was defined as a CT-RVEF of <45%. The primary outcome was a composite outcome, consisting of all-cause mortality and hospitalization due to heart failure, within 1 year after TTVR. Of 157 patients, 58 (36.9%) presented with CT-RVEF <45%. Procedural success and in-hospital mortality were comparable between patients with CT-RVEF <45% and ≥45%. However, CT-RVEF of <45% was associated with a higher risk of the composite outcome (hazard ratio: 2.99; 95% confidence interval: 1.65–5.41; P = 0.001), which had an additional value beyond two-dimensional echocardiographic assessments of RV function to stratify the risk of the composite outcome. In addition, patients with CT-RVEF ≥45% exhibited the association of procedural success (i.e. residual tricuspid regurgitation of ≤2+ at discharge) with a decreased risk of the composite outcome, while this association was attenuated in those with CT-RVEF <45% (P for interaction = 0.035). Conclusion CT-RVEF is associated with the risk of the composite outcome after TTVR, and a reduced CT-RVEF might attenuate the prognostic benefit of TR reduction. The assessment of 3D-RVEF by using CCT may refine the patient selection for TTVR. [ABSTRACT FROM AUTHOR]

Background: Periampullary cancer is a term for cancers arising in or in close proximity to the pancreas. Pancreatic cancer is the 3rd leading cause of cancer death for both sexes and while surgery is the only option for cure, chemotherapy is given in both the adjuvant and palliative settings. The aim of this study was to investigate any sex and gender differences in patients with pancreatic and other periampullary adenocarcinomas enrolled in a prospective, observational trial. Methods: The study cohort consists of the first 100 patients, 49 women and 51 men, enrolled in the Chemotherapy, Host Response and Molecular dynamics in Periampullary cancer (CHAMP) study, an ongoing study of patients undergoing neoadjuvant, adjuvant or first-line palliative chemotherapy treatment. Twenty-five patients had surgery with curative intent and subsequent adjuvant treatment, and 75 patients were treated with palliative chemotherapy. Data regarding health-related quality of life (HRQoL, EORTC-QLQ-C30) at baseline, demographic and clinicopathological factors were examined and stratification by treatment intention according to sex. Overall survival (OS) was calculated through Kaplan–Meier analysis. Results: There was a statistically significant difference between male and female patients treated with curative intent, with fewer women having undergone surgery (18 vs 7, p = 0.017), also after adjustment for age, tumor location and performance status. No statistical differences were found between the sexes regarding age, comorbidities, or clinicopathological factors. Before start of chemotherapy treatment, health-related quality of life (HRQoL) was lower in female than in male patients. However, HRQoL was not associated with performance status in female patients, whereas in male patients several HRQoL indicators were significantly positively associated with poorer performance status at baseline. Conclusions: This study shows no clear differences between the sexes regarding biological factors concluding that gender bias might be responsible for the discrepancy between men and women being offered curative surgery. The observed difference between women and men regarding the association between HRQoL and performance status is unprecedented. Altogether these findings underline the importance of taking gender into consideration when assessing eligibility for curative surgery in order to improve biological outcome and decrease suffering in both sexes. Trial registration: NCT03724994. [ABSTRACT FROM AUTHOR]

Inguinal hernia repair, according to Desarda, is a pure tissue surgical technique using external oblique fascia to reinforce the posterior wall of the inguinal canal. This has provided an impetus for the rethinking of guideline adherence toward minimally invasive and mesh-based surgery of inguinal hernia. In this study, a retrospective analysis of this technique was conducted in two German hospitals. Between 6/2013 and 12/2020, 120 operations were performed. Analysis included patient characteristics, duration of operation, length of hospital stay, and perioperative complications. Data were used to achieve a matched-pair analysis comparing Desarda to laparoscopic transabdominal preperitoneal (TAPP) hernia repair. Propensity scores were calculated based on five preoperative variables, including sex, age, American Society of Anesthesiology classification, localization, and width of the inguinal hernia in order to achieve comparability. Additionally, we assessed pain level and quality of life (QoL) 12 months postoperatively. The focus of our study was a comparison of QoL to a reference population and TAPP cohort. The study population consisted of 106 male and 14 female patients, and the median age was 37.5 years. The median operation time was 50 min, and the median length of hospital stay was 2 days. At a follow-up of 17 months, the median recurrence rate was 0.8%, and two cases of chronic postoperative pain were recorded. Postoperative QoL does not significantly differ between Desarda and TAPP. In contrast, Desarda patients had a significantly higher QoL compared with the reference population. In summary, Desarda's procedure is a good option as a pure tissue method for inguinal hernia repair. [ABSTRACT FROM AUTHOR]

Background: Fluid therapy, including the choice of a crystalloid or colloid infusion, the execution time of a volume bolus, and the expected volume need of a patient during surgery, varies greatly in clinical practice. Different goal directed fluid protocols have been developed, where fluid boluses guided by dynamic preload parameters are administered within a specific period. Objective: To study the efficacy of two fluid bolus infusion rates measured by the response of hemodynamic parameters. Design: Monocentric randomized controlled interventional trial. Setting: University hospital. Patients: Forty patients undergoing elective major spinal neurosurgery in prone position were enrolled, thirty-one were finally analyzed. Interventions: Patients were randomly assigned to receive 250 ml crystalloid and colloid boluses within 5 min (group 1) or 20 min (group 2) when pulse pressure variation (PPV) exceeded 14%. Main outcome measures: Changes in stroke volume (SV), mean arterial pressure (MAP), and catecholamine administration. Results: Group 1 showed a greater increase in SV (P = 0.031), and MAP (P = 0.014), while group 2 still had higher PPV (P = 0.005), and more often required higher dosages of noradrenalin after fluid administration (P = 0.033). In group 1, fluid boluses improved CI (P < 0.01), SV (P < 0.01), and MAP (P < 0.01), irrespective of whether crystalloids or colloids were used. In group 2, CI and SV did not change, while MAP was slightly increased (P = 0.011) only after colloid infusion. Conclusions: A fluid bolus within 5 min is more effective than those administered within 20 min and should therefore be the primary treatment option. Furthermore, bolus infusions administered within 20 min may result in volume overload without achieving relevant hemodynamic improvements. Trial registration: German Clinical Trials Register: DRKS00022917. [ABSTRACT FROM AUTHOR]

Purpose The American Association for the Study of Liver Diseases has developed a standard of care for the treatment of patients with spontaneous bacterial peritonitis (SBP). Evidence examining the adherence rate to these guideline recommendations is limited. This study aimed to determine the adherence rate to guideline-directed therapy for patients with cirrhosis hospitalized with SBP. Methods This institutional review board–approved retrospective cohort study conducted at a large academic hospital evaluated the adherence rate to guideline-directed therapy in adult patients with cirrhosis hospitalized with SBP. Included hospitalized patients had a documented diagnosis of cirrhosis and acute SBP. The adherence rate to guideline-directed therapy was determined by receipt of paracentesis within 24 hours of admission, request of Gram stain and culture tests, avoidance of fresh frozen plasma, receipt of albumin on days 1 and 3, receipt of empiric antibiotics within 6 hours, receipt of SBP prophylaxis, receipt of deep vein thrombosis prophylaxis, and offer of pneumococcal vaccination. Results A total of 110 patients were included. Provider adherence to goal-directed therapy was poor, with criteria met for only 10 (9.1%) patients. The therapies with the lowest adherence rates included SBP prophylaxis on discharge (54.5%), receipt of albumin on day 3 (42.7%), and offer of pneumococcal vaccination during admission (43.6%). Patients with a gastrointestinal consult were more likely than those without a consult to obtain albumin on day 1 (69.4% vs 36.8%, P = 0.001) and albumin on day 3 (52.8% vs 23.7%, P = 0.004). Conclusion This study demonstrated a lack of adherence to guideline-directed therapy for the management of SBP. [ABSTRACT FROM AUTHOR]

Background: Pain detection and treatment is a major challenge in the care of critically ill patients, rendered more complex by the need to take into consideration the risk of insufficient or excessive analgesia. The nociceptive flexion reflex threshold (NFRT) has become the established basis for measuring the level of analgesia in the perioperative context. However, it remains unclear whether NFRT measurement can be usefully applied to mechanically ventilated, analgosedated critically ill patients who are unable to communicate. Therefore, the aim of the present study was to investigate whether there is an association between the NFRT measurement and the Behavioral Pain Scale (BPS) in critically ill, analgosedated, and mechanically ventilated patients and whether the NFRT measurement can also detect potential excessive analgesia. Methods: This prospective, observational, randomized single-center pilot study included patients admitted to the surgical Intensive Care Unit of University Hospital Ulm, Germany, all of whom were analgosedated and intubated. Major exclusion criteria were defined as the need for the administration of neuromuscular blocking agents or neurological diseases associated with peripheral nerve conduction restriction. Initial NFRT and BPS measurements were conducted within 12 h after admission. A structured pain assessment was performed at least twice daily until extubation throughout the observation period thereafter (Group A: BPS + NFRT, Group B: BPS). Results: 114 patients were included in the study. NFRT is associated negatively with BPS. NFRT was almost twice as high in patients with a Richmond Agitation Sedation Scale (RASS) score of -5 than in patients with a RASS score ≥ -4 (RASS -5 – NFRT: 59.40 vs. RASS -4 – NFRT: 29.00, p < 0.001). Conclusions: NFRT measurement is associated negatively with the BPS in critically ill patients. NFRT measurement provides guidance for the evaluation of nociceptive processes in patients with RASS scores ≤ −4, in whom analgesia level is often difficult to assess. However, in order to identify excessive analgesia and derive therapeutic consequences, it is necessary to gradually decrease analgesics and sedatives until a stimulus threshold is reached at which the patient does not feel pain. Trial Registration: Retrospectively registered in the German Clinical Trials Register, registration number DRKS00021149, date of registration: March 26, 2020. https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00021149. [ABSTRACT FROM AUTHOR]

Background: To differentiate effects of ventricular asynchrony from an underlying hypocontractile cardiomyopathy this study aimed to enhance the understanding of functional impairment and structural remodeling in idiopathic left bundle-branch block (LBBB). We hypothesize, that functional asynchrony with septal flash volume effects alone might not entirely explain the degree of functional impairment. Hence, we suggest the presence of a superimposed contractile cardiomyopathy. Methods: In this retrospective study, 53 patients with idiopathic LBBB were identified and matched to controls with and without cardiovascular risk factors. Cardiovascular magnetic resonance (CMR) was used to evaluate cardiac function, volumes and myocardial fibrosis using native T1 mapping and late gadolinium enhancement (LGE). Septal flash volume was assessed by CMR volumetric measurements and allowed to stratify patients with systolic dysfunction solely due to isolated ventricular asynchrony or superimposed contractile impairment. Results: Reduced systolic LV-function, increased LV-volumes and septal myocardial fibrosis were found in patients with idiopathic LBBB compared to healthy controls. LV-volumes increased and systolic LV-function declined with prolonged QRS duration. Fibrosis was typically located at the right ventricular insertion points. Subgroups with superimposed contractile impairment appeared with pronounced LV dilation and increased fibrotic remodeling compared to individuals with isolated ventricular asynchrony. Conclusions: The presence of superimposed contractile impairment in idiopathic LBBB is crucial to identify patients with enhanced structural remodeling. This finding suggests an underlying cardiomyopathy. Future studies are needed to assess a possible prognostic impact of this entity and the development of heart failure. Trial registration: This study was retrospectively registered. [ABSTRACT FROM AUTHOR]

Background: Intensive care unit-acquired weakness syndrome (ICUAWS) can be a consequence of long-term mechanical ventilation. Despite recommendations of early patient mobilisation, little is known about the feasibility, safety and benefit of interval training in early rehabilitation facilities (ERF) after long-term invasive ventilation. Methods and Results: We retrospectively analysed two established training protocols of bicycle ergometry in ERF patients after long-term (> 7 days) invasive ventilation (n = 46). Patients conducted moderate continuous (MCT, n = 24, mean age 70.3 ± 10.1 years) or high-intensity interval training (HIIT, n = 22, mean age 63.6 ± 12.6 years). The intensity of training was monitored with the BORG CR10 scale (intense phases ≥ 7/10 and moderate phases ≤ 4/10 points). The primary outcome was improvement (∆-values) of six-minute-walk-test (6 MWT), while the secondary outcomes were improvement of vital capacity (VCmax), forced expiratory volume in 1 s (FEV1), maximal inspiratory pressure (PImax) and functional capabilities (functional independence assessment measure, FIM/FAM and Barthel scores) after 3 weeks of training. No adverse events were observed. There was a trend towards a greater improvement of 6 MWT in HIIT than MCT (159.5 ± 64.9 m vs. 120.4 ± 60.4 m; p =.057), despite more days of invasive ventilation (39.6 ± 16.8 days vs. 26.8 ± 16.2 days; p =.009). VCmax (∆0.5l ± 0.6 vs. ∆0.5l ± 0.3; p =.462), FEV1 (∆0.2l ± 0.3 vs. ∆0.3l ± 0.2; p =.218) PImax (∆0.8 ± 1.1 kPa vs. ∆0.7 ± 1.3pts; p =.918) and functional status (FIM/FAM: ∆29.0 ± 14.8pts vs. ∆30.9 ± 16.0pts; p =.707; Barthel: ∆28.9 ± 16.0 pts vs. ∆25.0 ± 10.5pts; p =.341) improved in HIIT and MCT. Conclusions: We demonstrate the feasibility and safety of HIIT in the early rehabilitation of ICUAWS patients. Larger trials are necessary to find adequate dosage of HIIT in ICUAWS patients. [ABSTRACT FROM AUTHOR]

Also, in Germany, 23 clinics perform 5,913 operations per year 9; this means on average 257 per clinic per year - a case number most likely at the end of the learning curve. The German patient organization for EA/TEF, KEKS, therefore decided to certify clinics on their own, setting 26 major reconstructions as the minimal number per clinic and year. [Extracted from the article]

Introduction: Heel pain is one of the common reasons why patients consult orthopaedic surgeons in an outpatient setting. The dorsal heel pain is often caused by a Haglund's deformity which is an exostosis of the posterior superior calcaneus. It often leads to Haglund's syndrome with calcaneal bursitis and Achilles tendinosis. This study aims to investigate the roll of MRI in diagnosis of Haglund's syndrome and its influence on therapy.Materials and Methods: We retrospectively analysed data of 45 patients which clinically and radiologically confirmed Haglund's deformity. Patients were divided into two groups that either did not receive MRI (MRI_0) or received MRI (MRI_1). To evaluate the significance, Fisher´s test was used. A statistical significance was assumed at p < 0.05.Results: The average age was 57.0 years. There was no significant difference in therapy comparing the groups MRI_0 and MRI_1. Haglund's syndrome was detected in 86.7% of all patients with Haglund's deformity.Conclusion: MRI does not influence the therapy of patients with Haglund's deformity. Therefore, the resources of this cost-intensive and limited type of investigation should be used elsewhere. In cases of atypical heel pain, the MRI might be useful. [ABSTRACT FROM AUTHOR]

Aim: The aim of this multi‐centre cohort study was to investigate the association of non‐surgical periodontal therapy (NST) on the oral health‐related quality of life (OHRQoL) in general and related to severity of periodontal disease and treatment modalities. Materials and Methods: One hundred and seventy‐two patients with periodontal disease from 18 dental practices were measured before and 6–8 weeks after NST using a standardized and validated OHRQoL instrument (Oral Health Impact Profile‐G14, OHIP‐G14). Another questionnaire was filled out by the dentists to evaluate the influence of treatment modalities and disease severity. Results: Overall, the mean value of the OHIP baseline improved significantly after NST (p < 0.0001). Furthermore, a significant negative association between the severity of periodontitis and OHRQoL could be detected, and only patients with moderate and severe periodontitis showed a significant improvement of OHIP mean values (p < 0.0001). The results also indicated a significant association of the practitioners (p = 0.0362) as well as treatment modalities (favouring systemic antibiotics, p = 0.0066) regarding the improvement of the patients' OHRQoL. Conclusion: This study showed that NST is positively associated with patients' oral health‐related quality of life. This association seems to depend on the disease severity and caregiver and treatment modality. [ABSTRACT FROM AUTHOR]

Background: Brain imaging is one of the most important diagnostic methods for evaluating headache during pregnancy. In this study, we aimed to identify anamnestic and clinical predictors for pathological brain imaging findings in pregnant women suffering from acute headache.Methods: We conducted a retrospective chart review of 151 pregnant women with acute headache between 2010 and 2016. We screened the medical records of these patients and analyzed radiological variables, including brain imaging frequency and modality, delay to imaging and imaging findings. In patients with brain imaging, we compared several anamnestic and clinical features between those with and without symptomatic pathological findings.Results: Half of the patients (50.3%) underwent brain imaging, mainly magnetic resonance imaging (MRI) including venography (53.9%) or MRI including both venography and arteriography (31.6%). Symptomatic pathological results could be observed in 27.6% of the patients with a brain scan. Patients in the first trimester with acute headache had a statistically higher risk for a symptomatic pathological imaging finding (p = 0.024). Strong pain intensity, a reduced level of consciousness and seizures were significantly associated with a symptomatic pathological imaging outcome across all stages of pregnancy.Conclusion: Brain imaging may reveal a secondary headache etiology in more than 25% of pregnant women presenting with acute headache. In particular, when the acute headache is of severe intensity, and the headache is accompanied by seizures or a change in consciousness, brain imaging is required. [ABSTRACT FROM AUTHOR]

Background/Aims: Arterial hypertension is one of the leading factors aggravating the course of chronic kidney disease (CKD). It seems that the novel parameters used in the assessment of the blood pressure (BP) load (i.e. central blood pressure, nighttime blood pressure) may be more precise in predicting the cardiovascular risk and the progression of CKD in comparison with the traditional peripheral blood pressure measurements in the office conditions. The aim of the study was to assess the impact of the central, or nighttime blood pressure on the progression of CKD in patients with mild or no-proteinuria (autosomal, dominant polycystic kidney disease or IgA nephropathy). Methods: In each of the enrolled 46 patients with CKD stage 3 or 4, serum creatinine concentration was assessed, eGFR (MDRD) was calculated, also central blood pressure and pulse wave velocity (PWV) was assessed and the 24-hour ambulatory blood pressure monitoring (ABPM) was conducted at the beginning of the study and then repeated after one-year observation period. Results: During the observation period mean eGFR decreased from 44.1 (33.2-50.6) mL/min to 36.7 (29.7-46.3) mL/min. No significant differences were observed in the peripheral blood pressure or central blood pressure parameters. After one-year observation period the values of diastolic blood pressure dipping during the night significantly decreased from 16 (13-19) mmHg to 12 (10-15) mmHg; p< 0.05. The values of systolic dipping during the night or the mean BP values recorded in ABPM did not change significantly. Additionally, no significant differences in the PWV values were found. In the multivariate regression model the change of serum creatinine concentration was explained by the initial diastolic dipping values. Conclusion: 1. In patients with CKD stages 3 or 4 and mild or no- proteinuria, peripheral and central blood pressure did not change significantly during a one-year observation period despite the significant decline of eGFR and seems not to participate in the CKD progression. 2. Reduced magnitude of the diastolic dipping, which reflects the increase of diastolic blood pressure load during the nighttime, may play an important role in the pathogenesis of deterioration of kidney function in these patients. [ABSTRACT FROM AUTHOR]

Introduction: The tyrosine kinase inhibitor (TKI) imatinib was rationally designed to target BCR-ABL1 which is constitutively activated in chronic myeloid leukemia (CML). Following the tremendous success in adults, imatinib also became licensed for treatment of CML in minors. The rarity of pediatric CML hampers the conduction of formal trials. Thus, imatinib is still the single TKI approved for CML treatment in childhood. Areas covered: This review attempts to provide an overview of the literature on pharmacology, pharmacokinetic, and pharmacogenetic of imatinib concerning pediatric CML treatment. Articles were identified through a PubMed search and by reviewing abstracts from relevant hematology congresses. Additional information was provided from the authors’ libraries and expertise and from our own measurements of imatinib trough plasma levels in children. Pharmacokinetic variables (e.g. alpha 1-acid glycoprotein binding, drug–drug/food–drug interactions via cytochrome P450 3A4/5, cellular uptake mediated via OCT-1-influx variations and P-glycoprotein-mediated drug efflux) still await to be addressed in pediatric patients systematically. Expert commentary: TKI response rates vary among different individuals and pharmacokinetic variables all can influence CML treatment success. Adherence to imatinib intake may be the most prominent factor influencing treatment outcome in teenagers thus pointing towards the potential benefits of regular drug monitoring. [ABSTRACT FROM PUBLISHER]

Purpose: The aim of the present study was to compare the daily activity and functionality in a patient cohort 12 months after total hip arthroplasty (THA) using a direct anterior approach with a healthy non-operated control population.Methods: Sixty-four patients who underwent THA and 59 healthy individuals (control) were assessed regarding their daily activity and joint functionality utilizing the Harris hip score (HHS), the extra short musculoskeletal functional assessment questionnaire (XSFMA), the Short Form 36 (SF-36) health survey and a Stepwatch™ Activity Monitor (SAM). Post-operative x-ray images after THA were analysed regarding inclination and stem positioning.Results: Twelve months after surgery, the average HHS showed no significant difference between both groups equalling 90.7 points in the THA patient group and 90.8 in the healthy volunteer group. The XSFMA functional index scores were 11.0 (THA) and 5.0 (control) while the bother index summed up to a score of 15.3 (THA) and 7.6 (control) respectively thus differing significantly (p < 0.001). Daily activity equalled 4227 (THA) and 4687 (control) load cycles per day (p = 0.327) while a number of 5658 (THA) and 6417 (control) steps per day (p = 0.011) was recorded. The SF-36 physical component scores were 47.3 (THA) and 50.6 (control) points while the psychometric properties added up to a score of 56.1 (THA) and 55.9 (control). The physical component was determined to be significantly different (p < 0.001) whereas no statistically significant difference could be shown for the psychometric properties (p = 0.511). The radiographic analysis revealed an average cup inclination of 39.9° without signs of migration. Stem positioning was neutral in 53% of all cases while 36% were graded varus and 11% valgus.Conclusion: In summary, our short-term results show an activity, functionality and quality of life for patients one year after THA comparable to healthy control individuals. [ABSTRACT FROM AUTHOR]

Purpose: To investigate optic nerve head (ONH) pallor quantitatively in patients with primary open-angle glaucoma (POAG) and in healthy subjects, and to examine the relationship to mean deviation in perimetry (MD), cup-disk ratio (CDR), and diameters of retinal vessels. Methods: A total of 89 POAG patients (67.6 ± 11.1 years) and 48 healthy subjects (63.3 ± 14 years) were included. A dual-bandpass transmission filter was introduced in the illumination path of the fundus camera of the Dynamic Vessel Analyzer (Imedos Systems UG) and two monochromatic images at different wavelenghts (548 ± 10 and 610 ± 10 nm) were recorded simultaneously. ONH pallor was defined as the quotient of light reflection in both spectral channels. Pallor values were averaged over four fields which were positioned on the ONH. The mean of these measurements was calculated. In 47 of 89 POAG patients diameters of retinal vessels were determined peripapillary. Results: In POAG, the ONH showed a significantly higher pallor value compared to healthy subjects (82.34 ± 19.28 vs. 62.67 ± 10.41,p< 0.001). ONH pallor was correlated to indicators used to estimate disease severity: MD (r= −0.565,p< 0.001) and CDR (r= 0.561,p< 0.001). The pallor value was associated to diameters of retinal arterioles (r= −0.313,p= 0.032) and venules (r= −0.397,p= 0.006). Conclusions: Pallor determined by this method was higher in POAG patients than in healthy subjects and increased in patients with advanced disease. ONH pallor might result from a reduced blood perfusion of the ONH or tissue atrophy accompanied by vessel obliteration in POAG. By measuring ONH pallor additional diagnostic information about the vitality of the neuroretinal rim might be gained in glaucoma patients. [ABSTRACT FROM AUTHOR]

Introduction: Multiple myeloma (MM) is still incurable due to resistance against various therapies. Thus, the identification of biomarkers predicting progression is urgently needed. Here, we evaluated four biomarkers in bone marrow and peripheral blood of MM patients for their prognostic significance. Materials & methods: Bone marrow- and peripheral blood plasma levels of FLT3-L, soluble TIE2, endostatin, and osteoactivin were determined in patients with monoclonal gammopathy of undetermined significance (MGUS, n = 14/n = 4), patients with newly diagnosed MM (NDMM, n = 42/n = 31) and patients with relapsed/refractory MM (RRMM, n = 27/n = 16) by sandwich ELISA. Results: Median FLT3-L expression increased from MGUS (58.77 pg/ml in bone marrow; 80.40 pg/ml in peripheral blood) to NDMM (63.15 pg/ml in bone marrow; 85.05 pg/ml in peripheral blood) and was maximal in RRMM (122 pg/ml in bone marrow; 160.47 pg/ml in peripheral blood; NDMM vs. RRMM p<0.001). A cut-off value of FLT3-L >92 pg/ml in bone marrow and >121 pg/ml in peripheral blood was associated with relapse or refractoriness in MM patients. FLT3-L was found to be a high predictive marker for discrimination between NDMM and RRMM as well in bone marrow as in peripheral blood (AUC 0.75 in bone marrow; vs 0.84 in peripheral blood). Conclusion: High levels of FLT3-L in bone marrow and peripheral blood of MM patients identify patients with progressive disease and are associated with relapse or refractoriness in MM patients. FLT3-L could be useful as a marker to identify RRMM patients and should be evaluated as target for future therapies. [ABSTRACT FROM AUTHOR]

Purpose Selective laser trabeculoplasty ( SLT) is known to reduce intraocular pressure (IOP) effectively. The aim of this study, however, was to evaluate the effect of SLT on ocular haemodynamics. Methods A total of 69 eyes of 69 patients (age 67.8 ± 9.9 years) with already treated primary open-angle glaucoma who were assigned for SLT for further IOP reduction were consecutively enrolled in this prospective interventional case series. Intraocular pressure, the ocular pulse amplitude ( OPA), ocular pulse volume ( OPV) and pulsatile ocular blood flow ( pOBF) were assessed with the Ocular Blood Flow Analyzer prior to and 3 months after SLT. Results Intraocular pressure was statistically significantly reduced from 16.0 ± 5.4 mmHg to 12.8 ± 4.0 mmHg (p = 0.001). The OPA did not change (p = 0.783) after IOP reduction following SLT. OPV and pOBF increased statistically significantly. OPV increased from 7.33 ± 3.05 to 8.59 ± 3.35 μl (17.2%; p = 0.001) and pOBF from 17.11 ± 5.42 to 19.74 ± 6.59 μl/s (15.4%; p = 0.002). Conclusion Selective laser trabeculoplasty probably does not induce any pharmacological changes effecting systemic blood pressure or ocular blood flow as topical IOP-lowering medication might do, nor does it change biomechanical properties of the eye as surgery could. Therefore, an increase in ocular blood flow following SLT can only be explained by the reduction in IOP and might be a sign of dysfunctional autoregulation in glaucoma patients. [ABSTRACT FROM AUTHOR]

The majority of tinnitus patients are affected by chronic idiopathic tinnitus, and almost 60 different treatment modalities have been reported. The present study is a multidisciplinary systematic analysis of the evidence for the different forms of treatment for chronic tinnitus. The results are used to form the basis of an S3 guideline. A systematic search was carried out in PubMed and the Cochrane Library. The basis for presenting the level of evidence was the evidence classification of the Oxford Centre of Evidence-based Medicine. Whenever available, randomised controlled trials were given preference for discussing therapeutic issues. All systematic reviews and meta-analyses were assessed for their methodological quality, and effect size was taken into account. As the need for patient counselling is self-evident, specific tinnitus counselling should be performed. Due to the high level of evidence, validated tinnitus-specific, cognitive behavioural therapy is strongly recommended. In addition, auditory therapeutic measures can be recommended for the treatment of concomitant hearing loss and comorbidities; those should also be treated with drugs whenever appropriate. In particular, depression should be treated, with pharmacological support if necessary. If needed, psychiatric treatment should also be given on a case-by-case basis. With simultaneous deafness or hearing loss bordering on deafness, a CI can also be indicated. For auditory therapeutic measures, transcranial magnetic or direct current stimulation and specific forms of acoustic stimulation (noiser/masker, retraining therapy, music, and coordinated reset) for the treatment of chronic tinnitus the currently available evidence is not yet sufficient for supporting their recommendation. [ABSTRACT FROM AUTHOR]

Background Cerebral cavernous malformations ( CCM) are vascular lesions of the central nervous system that can be found in sporadic or autosomal dominantly inherited forms and manifest with headaches, seizures, and hemorrhagic stroke. The precise proportion of de novo mutations in the CCM1, CCM2, and CCM3 genes remains unknown. Methods We here present a series of six trios with de novo mutations that have been analyzed by amplicon deep sequencing to differentiate between constitutional and postzygotic mutations. Results In one case, allelic ratios clearly indicated mosaicism for a CCM3 splice site mutation found in blood and buccal mucosa of a 2-year-old boy with multiple CCMs. The remaining five de novo mutations proved to be constitutional. In addition to three CCM3, two CCM1, and one CCM2 de novo point mutations, a deletion of the entire CCM3 gene was identified in an index case that most likely originated from an early postzygotic event. These are the first high-level mosaic mutations reported in blood samples of isolated CCM cases. Conclusion Our data demonstrate that de novo mutations in CCM1-3 might be more frequent than previously thought. Furthermore, amplicon deep sequencing is useful to discriminate between patients with constitutional and postzygotic mutations, and thereby improves genetic counseling. [ABSTRACT FROM AUTHOR]

A universal protocol determining the number of leeches and their application time does not exist. The aim of this study, therefore, is to quantify perfusion dynamics in venous congested tissues after leech application to get more detailed information about changes due to leech-induced skin microcirculation and to evaluate the usability of the Oxygen to See (O2C) device in terms of determining the appropriate number of leeches and the duration of therapy. Twelve patients with the need for leech therapy participated in the study. Perfusion dynamics of the congested tissue was assessed using the O2C device, which determines blood flow (BF), the relative amount of hemoglobin (rHB), and the oxygen saturation (SO2). Measurements were carried out before leech application and on various intervals like 10 minutes, one hour, and three hours after leech application. The leech application effectuated after 10 minutes a nonsignificant perfusion improvement, which further increased after one hour with a significant reduction of the relative amount of hemoglobin and a significant increase of blood flow and oxygen saturation (BF= +56.7%; rHB= −25.5%; SO2= +53.7%). After three hours, the values returned to the levels before leech administration. In two cases, in which further administration of leeches within the measurement period was necessary, no substantial perfusion changes were obtained. The results of this study forms a more precise pattern of microcirculatory changes of leech therapy in congested tissues. According to our measurements a venous drainage improvement can be expected in congested tissue one hour after leech administration. The O2C seems to be a useful method to determine the appropriate number and duration of leech therapy. [ABSTRACT FROM AUTHOR]

. Purpose: To investigate the relationship between central corneal thickness (CCT) and optic disc size in patients with primary open-angle glaucoma (POAG) in a hospital-based population. Methods: Data for the right eyes of 1435 White patients with POAG were included in a retrospective hospital-based study. All eyes underwent optic nerve head imaging using Heidelberg Retina Tomograph II (HRT II; Heidelberg Engineering, Heidelberg, Germany) and CCT measurement by ultrasound corneal pachymetry. Eyes with prior intraocular or corneal surgery were excluded. Low-quality HRT II images were also excluded. The impact of age, gender, CCT, intraocular pressure, cylindrical and spherical refractive error as independent factors on optic disc size was investigated in a multiple linear regression analysis. Results: The data for 1104 right eyes qualified for participation in the study. The median age of these patients was 65 years. The median CCT was 547 μm (25th-75th percentile 522-575 μm). The median optic disc size was 2.21 mm2 (25th-75th percentile 1.89-2.60 mm2). Multiple linear regression analysis revealed that age (p = 0.001), CCT (p = 0.001) and spherical equivalent (p = 0.049) were correlated to disc size according to the following formula: disc area = −0.004 × age − 0.001 × CCT − 0.014 × spherical equivalent +3.290. R2 of the whole model was 0.021. Univariate regression analysis between age and disc area provided R2 = 0.008 with p = 0.002. Univariate regression analysis between disc area and CCT provided R2 = 0.005 with p = 0.02. Conclusion: In this retrospective hospital-based study we could not detect a clinically relevant correlation between optic disc size and CCT. The correlation between CCT and disc size and between age and disc size were statistically significant, but the R2 values were very low. The results of the study are biased because of its hospital-based design, so the results of the study need to be confirmed in a large population-based study. [ABSTRACT FROM AUTHOR]

Background Long-term data on clinical outcomes of restorations attached to implants via zinc oxide ( ZnO) cement have been sparse. Purpose The purpose of this study was to retrospectively investigate decementation rates and peri-implant tissue status of implant-supported fixed restorations retained by ZnO cement. Materials and Methods Between 1989 and 2003, 63 partially edentulous patients received 93 implants. Of these, 27 patients received 36 screwed single crowns ( SC) and served as a control ( C group). The other 36 patients had their restorations cemented using ZnO cement. They were subdivided into a SC group and a fixed dental prosthesis ( FDP) group. After between 10 and 23 years (mean: 13.22 ± 3.21), all decementation events and peri-implant soft tissue status were evaluated using patient records. Results Decementation was assessed in 57 implants supporting 30 SCs and 16 FDPs. Five cases of decementation (8.77%) were recorded after a mean of 9.27 ± 7.05 years (range: 4.81-21.79). In the control group of vertically screwed SCs, five events of screw loosening (13.89%) were recorded in five patients (18.52%) after a mean of 5.84 ± 5.96 years (range: 0.56-15.05) within a 14.30 year observation period. No cases of peri-implantitis were observed in any group. The mean values of periodontal probing depths and bleeding on probing (BOP+) were 3.74 mm and 31.58%, respectively, for ZnO-cemented restorations, versus 3.76 mm and 25%, respectively, for the C group. No significant correlations regarding technical/biologic complications between the groups were detected. Conclusions Within the limitations of this study, we conclude that the use of ZnO cement provides sufficient retention of implant-supported fixed restorations over long periods without biologic complications in form of peri-implantitis. [ABSTRACT FROM AUTHOR]

Purpose To evaluate the effect of selective laser trabeculoplasty ( SLT) on ocular biomechanics as measured with the ocular response analyzer ( ORA, AMETEK Inc. and Reichert Inc.). Methods In a prospective case series, 52 eyes of 52 patients (aged 66.6 ± 9.6 years) with insufficient intraocular pressure ( IOP) control despite maximum tolerated medical therapy underwent SLT (Solo™ SLT, Ellex Inc.) for further IOP reduction. Goldmann-correlated IOP ( IOPg), corneal-compensated IOP ( IOPcc), corneal hysteresis ( CH) and the corneal resistance factor ( CRF) were measured with the ORA prior to and at least 4 weeks following SLT. Results IOPg decreased statistically significantly from 18.0 ± 6.4 to 14.8 ± 3.8 mmHg and IOPcc from 20.2 ± 6.5 to 16.7 ± 3.4 mmHg (p < 0.001). CH increased from 8.53 ± 2.03 to 9.12 ± 1.83 mmHg (p = 0.028) and CRF decreased from 9.58 ± 2.18 to 9.1 ± 2.1 mmHg (p = 0.037), which was statistically significant. Correcting the CH and CRF data for the influence of IOP reduction with a covariance analysis, however, resulted in an unchanged CH ( IOPg adjusted: p = 0.318; IOPcc adjusted: p = 0.468) and CRF ( IOPg adjusted: p = 0.320; IOPcc adjusted: p = 0.464) after SLT. Conclusion Selective laser trabeculoplasty does not change corneal biomechanical properties as measured with the ORA in already pretreated patients with glaucoma. The measured increase in CH and decrease in CRF can be solely explained by IOP reduction. [ABSTRACT FROM AUTHOR]

Background: Podocalyxin-like protein (PODXL) is a cell surface transmembrane glycoprotein, the expression of which has been associated with poor prognosis in a range of malignancies. The aim of this study was to investigate the impact of PODXL expression on survival in esophageal and gastric adenocarcinoma. Methods: The study cohort consists of a consecutive series of 174 patients with esophageal (including the gastroesophageal junction) or gastric adenocarcinoma, surgically treated between 2006 and 2010 and not subjected to neoadjuvant treatment. Immunohistochemical expression of PODXL was assessed in tissue microarrays with cores from primary tumors, lymph node metastases, intestinal metaplasia and adjacent normal epithelium. Survival analyses were performed on patients with no distant metastases and no macroscopic residual tumor. Results: In the majority of cases, expression of PODXL was significantly higher in cancer cells compared to normal epithelial cells and was significantly associated with lymph node metastases and high grade tumors. In esophageal adenocarcinoma, Kaplan-Meier analyses revealed that patients with PODXL negative tumors had a superior time to recurrence (TTR) and overall survival (OS) compared to patients with PODXL positive tumors. In gastric adenocarcinoma, patients with PODXL negative tumors had a superior TTR and a trend towards an improved OS. In esophageal and gastric adenocarcinoma combined, the prognostic significance of PODXL expression on TTR was confirmed in unadjusted Cox regression analysis (HR = 5.36, 95 % CI 1.68-17.06, p = 0.005) and remained significant in the adjusted model (HR = 3.39, 95 % CI 1.01-11.35, p = 0.048). Moreover, the impact of PODXL expression on OS was also confirmed in unadjusted analysis (HR = 2.52, 95 % CI 1.31-4.85, p = 0.006) and remained significant in the adjusted model (HR = 2.03, 95 % CI 1.04-3.98, p = 0.039). Conclusions: In esophageal and gastric adenocarcinoma, PODXL expression is an independent prognostic biomarker for reduced time to recurrence and poor overall survival. This is the first report on the prognostic role of PODXL in esophageal adenocarcinoma and validates recent findings in gastric cancer. [ABSTRACT FROM AUTHOR]

Katie Hampson and colleagues describe their experience of developing and deploying a large-scale rabies surveillance system based on mobile phones in southern Tanzania. [ABSTRACT FROM AUTHOR]

One major aim of the neurological rehabilitation of patients with severe disorders of consciousness (DOC) is to enhance patients’ arousal and ability to communicate. Mobilization into a standing position by means of a tilt table has been shown to improve their arousal and awareness. However, due to the frequent occurrence of syncopes on a tilt table, it is easier to accomplish verticalization using a tilt table with an integrated stepping device. The objective of this randomized controlled clinical trial was to evaluate the effectiveness of a tilt table therapy with or without an integrated stepping device on the level of consciousness. A total of 50 participants in vegetative or minimally conscious states 4 weeks to 6 month after injury were treated with verticalization during this randomized controlled trial. Interventions involved ten 1-hour sessions of the specific treatment over a 3-week period. Blinded assessors made measurements before and after the intervention period, as well as after a 3-week follow-up period. The coma recovery scale-revised (CRS-R) showed an improvement by a median of 2 points for the group receiving tilt table with integrated stepping (Erigo). The rate of recovery of the group receiving the conventional tilt table therapy significantly increased by 5 points during treatment and by an additional 2 points during the 3-week follow-up period. Changes in spasticity did not significantly differ between the two intervention groups. Compared to the conventional tilt table, the tilt table with integrated stepping device failed to have any additional benefit for DOC patients. Verticalization itself seems to be beneficial though and should be administered to patients in DOC in early rehabilitation. Trial Registration: Current Controlled Trials Ltd (), identifier number [ABSTRACT FROM AUTHOR]

Background: Unlike the well-established association between sleep disordered breathing (SDB) and chronic heart failure, the relationship between SDB and severe aortic stenosis (AS) is not well investigated. Given the increasing prevalence of AS, and the improving prognosis of high risk AS patients attributable to transcatheter aortic valve implantation (TAVI), the prevalence and impact of SDB needs to be better understood. Methods and Results: In this study, 140 patients with severe AS underwent polygraphy prior to TAVI. Clinical and hemodynamic parameters were recorded. Patients were followed for 573±405 days. We found that 99/140 patients (71%) had SDB with a mean apnoea-hypopnoea-index of 24±17/h. SDB was mild in 27%, moderate in 23% and severe in 21% of patients. In addition, 35 patients (25%) had obstructive sleep apnoea (OSA), whereas 64 patients (46%) had central sleep apnoea (CSA). Patients with OSA had predominantly mild SDB (20/38 pts.), and patients with CSA mostly had severe SDB (24/29 pts.). The prevalence and distribution of OSA and CSA were independent of left ventricular function. Overall, 1 and 2 year survival rates (74% and 71%, resp.) did not differ significantly between patients without SDB or those with OSA and CSA (p=0.81). Conclusions: SDB, with a preponderance of CSA, was found to be highly prevalent in patients with high-grade AS scheduled for TAVI. SDB prevalence was independent of left ventricular function. Mortality after TAVI was not influenced by the type or severity of SDB. [ABSTRACT FROM AUTHOR]

Background: Hazardous alcohol use in psychiatric patients may increase the risk of the development of a substance use disorder and negatively affect the course of the psychiatric disorder. Aims: To investigate the prevalence of hazardous alcohol and drug use in a Swedish psychiatric outpatient population with particular focus on hazardous alcohol consumption and assess relationships of hazardous alcohol use to sex, age and psychiatric diagnosis. Methods: General psychiatric outpatients, n = 1,679, completed a self-rating Alcohol Use Disorders Identification Test (AUDIT). Results: Hazardous or harmful alcohol habits occurred among 22% of all women and 30% of all men with higher prevalence among younger patients. Nine percent of all women and 22 % of all men reported binge drinking. Binge drinking was more frequent in younger subjects. Women with a personality disorder diagnosis had a higher frequency of at risk drinking. Apart from that, psychiatric diagnosis was unrelated to rate of hazardous drinking. Conclusions: Hazardous alcohol use was common in this psychiatric outpatient population. With regard to possible risks related to drinking in psychiatric patients, alcohol habits should be assessed as a part of good clinical practice. [ABSTRACT FROM AUTHOR]

BACKGROUND The Pragmatic, Randomized Optimal Platelets and Plasma Ratios (PROPPR) trial was a randomized clinical trial comparing survival after transfusion of two different blood component ratios for emergency resuscitation of traumatic massive hemorrhage. Transfusion services supporting the study were expected to provide thawed plasma, platelets, and red blood cells within 10 minutes of request. STUDY DESIGN AND METHODS At the 12 Level 1 trauma centers participating in PROPPR, blood components transfused and delivery times were tabulated, with a focus on universal donor (UD) plasma management. The adequacy of site plans was assessed by comparing the bedside blood availability times to study goals and the new American College of Surgeons guidelines. RESULTS Eleven of 12 sites were able to consistently deliver 6 units of thawed UD plasma to their trauma-receiving unit within 10 minutes and 12 units in 20 minutes. Three sites used blood group A plasma instead of AB for massive transfusion without complications. Approximately 4700 units of plasma were given to the 680 patients enrolled in the trial. No site experienced shortages of AB plasma that limited enrollment. Two of 12 sites reported wastage of thawed AB plasma approaching 25% of AB plasma prepared. CONCLUSION Delivering UD plasma to massively hemorrhaging patients was accomplished consistently and rapidly and without excessive wastage in high-volume trauma centers. The American College of Surgeons Trauma Quality Improvement Program guidelines for massive transfusion protocol UD plasma availability are practicable in large academic trauma centers. Use of group A plasma in trauma resuscitation needs further study. [ABSTRACT FROM AUTHOR]

Background: Approximately 20% of patients with bipolar disorder experience mixed states. Mixed states are associated with more comorbidity, poorer treatment response and prognosis, increased relapse rate, and decreased functioning. This study aimed to produce in-depth knowledge about bipolar patients' quality of life (QoL) and functioning related to mixed states. Sampling and Methods: This study used qualitative research methods. A semi-structured interview guide based on a literature study was applied in interviews with 6 remitted bipolar I patients having experienced mixed states. A medical anthropological approach was applied to analyse the data. Results: Participants described mixed states as worse than other bipolar disorder states and their residual symptoms were prolonged. Mixed states affected the functioning of patients in key life domains such as self-esteem, family, love and social life, physical well-being, and working capability. Conclusions: Mixed states may severely affect the QoL and functioning of bipolar patients. Our results indicate that improving these should be a main goal of patient treatment. With an aim of adequately identifying and treating mixed states, our findings highlight the need for knowledge about this particularly severe expression of bipolar disorder. These results should be confirmed in a larger sample of patients with varying socioeconomic status. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Osteosarcoma (OS), a bone tumor, exhibit a complex karyotype. On the genomic level a highly variable degree of alterations in nearly all chromosomal regions and between individual tumors is observable. This hampers the identification of common drivers in OS biology. To identify the common molecular mechanisms involved in the maintenance of OS, we follow the hypothesis that all the copy number-associated differences between the patients are intercepted on the level of the functional modules. The implementation is based on a network approach utilizing copy number associated genes in OS, paired expression data and protein interaction data. The resulting functional modules of tightly connected genes were interpreted regarding their biological functions in OS and their potential prognostic significance. We identified an osteosarcoma network assembling well-known and lesser-known candidates. The derived network shows a significant connectivity and modularity suggesting that the genes affected by the heterogeneous genetic alterations share the same biological context. The network modules participate in several critical aspects of cancer biology like DNA damage response, cell growth, and cell motility which is in line with the hypothesis of specifically deregulated but functional modules in cancer. Further, we could deduce genes with possible prognostic significance in OS for further investigation (e.g. EZR, CDKN2A, MAP3K5). Several of those module genes were located on chromosome 6q. The given systems biological approach provides evidence that heterogeneity on the genomic and expression level is ordered by the biological system on the level of the functional modules. Different genomic aberrations are pointing to the same cellular network vicinity to form vital, but already neoplastically altered, functional modules maintaining OS. This observation, exemplarily now shown for OS, has been under discussion already for a longer time, but often in a hypothetical manner, and can here be exemplified for OS. [ABSTRACT FROM AUTHOR]

Background: The cardiotonic steroid marinobufagenin (MBG) is increasingly suggested to be responsible for some of the cardiovascular injury that has been previously attributed to aldosterone. We examined the clinical correlates of circulating MBG concentrations in hypertensive patients and tested the hypothesis that MBG serves as a reliable diagnostic tool for detecting primary aldosteronism (PA). Methods: Plasma MBG concentrations (mean: 0.51 ± 0.25 nmol/l) were measured in the morning fasting samples in 20 patients with PA and 20 essential hypertensive (EH) controls matched for age, sex, body mass index, renal function, urinary sodium and intake of antihypertensive medication (mean age: 51.6 years; 52.2% women). Results: Overall, plasma MBG was directly correlated with plasma aldosterone, aldosterone to active renin ratio (AARR), diastolic blood pressure, mean carotid intima-media thickness, serum sodium, urinary protein to creatinine ratio and inversely with serum potassium levels. Plasma MBG levels were significantly higher in patients with PA compared to EH (mean: 0.68 ± 0.12 versus 0.35 ± 0.24 nmol/l; p < 0.001). ROC analysis yielded a greater AUC for plasma MBG compared to the AARR, PAC and serum potassium levels for detecting PA. Youden's Index analyses yielded the optimal plasma MBG cut-off score for diagnosing PA at > 0.49 nmol/l with specificity and sensitivity values of 0.85 and 0.95, respectively, which were higher than those at the optimum AARR cut-off at > 3.32 ng/dl/µU/ml. Conclusions: In a well-characterized cohort, values of plasma MBG were significantly related to clinical correlates of cardiovascular and renal disease. Plasma MBG emerged as a valuable alternative to the AARR for screening of PA. [ABSTRACT FROM AUTHOR]

Objective: To characterize the etiologic agent (WA1) of the first reported case of babesiosis acquired in Washington State.Design: Case report, and serologic, molecular, and epizootiologic studies.Setting: South-central Washington State.Patient: A 41-year-old immunocompetent man with an intact spleen who developed a moderately severe case of babesiosis.Measurements: Serum specimens from the patient were assayed by indirect immunofluorescent antibody (IFA) testing for reactivity with seven Babesia species and with WA1, which was propagated in hamsters inoculated with his blood. A Babesia-specific, ribosomal-DNA (rDNA) probe was hybridized to Southern blots of restriction-endonuclease-digested preparations of DNA from WA1, Babesia microti, and Babesia gibsoni. Serum specimens from 83 family members and neighbors were assayed for IFA reactivity with WA1 and B. microti. Small mammals and ticks were examined for Babesia infection.Results: The patient's serum had very strong IFA reactivity with WA1, strong reactivity with B. gibsoni (which infects dogs), but only weak reactivity with B. microti. DNA hybridization patterns with the rDNA probe clearly differentiated WA1 from B. gibsoni and B. microti. Four of the patient's neighbors had IFA titers to WA1 of 256. The tick vector and animal reservoir of WA1 have not yet been identified, despite trapping 83 mammals and collecting 235 ticks.Conclusions: WA1 is morphologically indistinguishable but antigenically and genotypically distinct from B. microti. Some patients elsewhere who were assumed to have been infected with B. microti may have been infected with WA1. Improved serodiagnostic and molecular techniques are needed for characterizing Babesia species and elucidating the epidemiology of babesiosis, an emergent zoonosis. [ABSTRACT FROM AUTHOR]

Background. The aim of this work was to evaluate the clinical effectiveness of acupuncture and its impact on the immune system in comparison to loratadine in the treatment of persistent allergic rhinitis caused by house dust mites. Methods. In this study, 24 patients suffering from persistent allergic rhinitis induced by house dust mites were treated either with acupuncture (n = 15) orwith loratadine (n = 9). The evaluation of the data was based on the subjective and the objective rhinoconjunctivitis symptom scores, specific and total IgE, and interleukins (IL-4, IL-10, and IFN-γ) as markers for the activity of Th1 or Th2 cells. Results. The treatments with acupuncture as well as with loratadine were considered effective in the patients' subjective assessment, whereby the effect of the acupuncture tended to be assessed as more persistent after the end of treatment. A change in the specific or the total IgE was not detectable in either group. The interleukin profile showed the tendency of an increasing IL-10 value in the acupuncture group. The results of the study show that the effectiveness of acupuncture is comparable to that of loratadine. Conclusion. Acupuncture is a clinically effective form of therapy in the treatment of patients suffering from persistent allergic rhinitis. The results indicate the probability of an immunomodulatory effect. [ABSTRACT FROM AUTHOR]

Background—Lipoprotein(a) (Lp(a)) hyperlipoproteinemia is a major risk factor for cardiovascular disease, which is not affected by treatment of other cardiovascular risk factors. This study sought to assess the effect of chronic lipoprotein apheresis (LA) on the incidence of cardiovascular events in patients with progressive cardiovascular disease receiving maximally tolerated lipid-lowering treatment. Methods and Results—In a prospective observational multicenter study, 170 patients were investigated who commenced LA because of Lp(a)-hyperlipoproteinemia and progressive cardiovascular disease. Patients were characterized regarding plasma lipid status, lipid-lowering drug treatment, and variants at the LPA gene locus. The incidence rates of cardiovascular events 2 years before (y-2 and y-1) and prospectively 2 years during LA treatment (y+1, y+2) were compared. The mean age of patients was 51 years at the first cardiovascular event and 57 years at the first LA. Before LA, mean low- density lipoprotein cholesterol and Lp(a) were 2.56±1.04 mmol·L–1 (99.0±40.1 mg·dL–1) and Lp(a) 3.74±1.63 μmol·L–1 (104.9±45.7 mg·dL–1), respectively. Mean annual rates for major adverse coronary events declined from 0.41 for 2 years before LA to 0.09 for 2 years during LA (P<0.000 I). Event rates including all vascular beds declined from 0.61 to 0.16 (P<0.000l). Analysis of single years revealed increasing major adverse coronary event rates from 0.30 to 0.54 (P=0.001) for y-2 to y-l before LA, decline to 0.14 from y-l to y+1 (P<0.0001) and to 0.05 from y+1 to y+2 (P=0.014). Conclusions—In patients with Lp(a)-hyperlipoproteinemia, progressive cardiovascular disease, and maximally tolerated lipid-lowering medication, LA effectively lowered the incidence rate of cardiovascular events. Clinical Trial Registration—URL: https://drks-neu.uniklinik-freiburg.de. Unique identifier: DRKS00003119. [ABSTRACT FROM AUTHOR]

Introduction and hypothesis: Bladder pain syndrome/interstitial cystitis (BPS/IC) is identified based on subjective symptoms which lead to heterogeneous patient populations. Previous studies using gene expression arrays for BPS/IC with Hunner’s lesions [European Society for the Study of Interstitial Cystitis (ESSIC) type 3C], a subtype of the condition discernible by cystoscopy, have revealed characteristic immune responses and urothelial abnormalities. This current study aimed to further characterize this subtype using a gene expression panel. We hypothesized that B-cell activation with high levels of urinary antibody concentration would be found. Methods: Cold-cup bladder biopsies, catheterized urine and blood were collected from 15 BPS/IC ESSIC type 3C patients, 11 non-inflammatory overactive bladder (OAB) patients and eight healthy controls. Gene expression in biopsies was quantified by real-time quantitative polymerase chain reaction (RT-qPCR), immunohistochemistry was performed on bladder tissue and urinary immunoglobulins G and A were quantified by enzyme-linked immunosorbent assay. Statistical analyses included the Kruskal-Wallis test for non-parametric data and post hoc tests identified differences between groups. Results: High expression of T- and B-cell markers ( CTLA4, CD20, CD79A, IGH@), low expression of urothelial markers ( KRT20, UPK1B, UPK3A), focal lymphoid aggregates in the submucosa and high immunoglobulin concentration in urine were found exclusively in BPS/IC ESSIC type 3C patients. Results for OAB were in intermediate ranges between the other two groups and UPK1B even reached significantly lower expression when compared to healthy controls. Conclusions: BPS/IC ESSIC type 3C is characterized by a local adaptive immune response with elevated urinary antibody concentrations. Quantification of urinary immunoglobulin levels could be used for a non-invasive diagnosis of BPS/IC ESSIC type 3C. [ABSTRACT FROM AUTHOR]

Background: The simultaneous assessment of high-sensitivity cardiac troponin T (hscTnT) and NT-proBNP for predicting death in stable coronary artery disease (CAD) has yet not been examined. We investigated the additional contribution of hscTnT to the risk of mortality prediction of NT-proBNP in patients with stable CAD. Methods: We studied 1469 patients with stable CAD enrolled in the Ludwigshafen Risk and Cardiovascular Health Study (LURIC). hscTnT and NT-proBNP were measured in baseline samples using immunoassays (Roche Diagnostics, Germany). Results: Thirty-five percent (n=525) of the patients died during a median follow-up of 7 and a half years. In total 59.0% of the non-survivors and 25.2% of the survivors exhibited concentrations of hscTnT≥14 ng/L. Logistic regression analysis identified hscTnT and NT-proBNP as independent risk markers for short-term (1-year follow-up) and long-term (9-years follow-up) mortality. ROC curve analysis determined optimal univariate cut-offs at 14 ng/L and 443 µg/L for hscTnT (AUC 0.725, p<0.0001) and NT-proBNP (AUC 0.742, p<0.0001), respectively. Kaplan-Meier survival analysis based on optimized cut-offs for the simultaneous determination of both biomarkers confirmed the usefulness of additive hscTnT especially in prediction of short-term mortality. The prognostic benefit of the combined assessment of hscTnT and NT-proBNP could be confirmed by a significantly increased reclassification index (NRI) of 24.2%. Conclusions: The majority of non-survivors exhibited increased hscTnT concentrations above 14 ng/L. The simultaneous determination of NT-proBNP and hscTnT was superior for risk stratification compared to determining either marker alone. Especially the prediction of the clinically important 1-year mortality was significantly improved by addition of hscTnT to NT-proBNP. [ABSTRACT FROM AUTHOR]

Transcatheter aortic valve implantation (TAVI) has emerged as a therapeutical option in patients with aortic stenosis. The methodology has evolved rapidly throughout the last decade. Nowadays, peri-procedural circulatory support, surgical vascular access, general anesthesia and mechanical ventilation are mainly reserved for selected patients. However, numerous challenges need to be addressed in order to further improved outcome of this distinct cohort: patient selection in general, vascular access strategies, long-term valve performance and paravalvular leakage. Another key issue is the risk of cerebrovascular events related to TAVI. In this article, the authors review the current literature on the risk of cerebrovascular events, the underlying mechanisms, the diagnostic read-outs of cerebral injury and their prognostic value, and ultimately discuss conceivable concepts for prevention of stroke associated with TAVI. [ABSTRACT FROM AUTHOR]

Aims: Previous studies have shown that membranous expression of podocalyxin-like protein (PODXL) is associated with poor prognosis in colorectal cancer (CRC). In this study, we compared PODXL expression in primary CRC and synchronous lymph node metastases. We further analyzed whether its expression changed in rectal tumours after neoadjuvant radiation therapy. Methods and results: The studied cohort consists of 73 consecutive patients from the South-Swedish Colorectal Cancer Biobank. Immunohistochemical PODXL expression was examined on full-face sections from all primary tumours and all 140 available lymph node metastases from 31 cases. Membranous PODXL expression was denoted in 18/73 (24,7%) primary tumours, with a high concordance between primary and metastatic lesions. While all negative primary tumours had negative metastases, some PODXL positive primaries had a varying proportion of positive and negative metastatic lymph nodes. PODXL expression was also found to be mainly unaltered in preand post-irradiation surgically resected tumour specimens in rectal cancer patients (n=16). Conclusions: The findings in this study suggest that analysis of PODXL expression in the primary tumour is sufficient for its use as a prognostic and treatment predictive biomarker in CRC, also in patients with metastatic disease. [ABSTRACT FROM AUTHOR]

Introduction This prospective nonrandomized study compared the safety and efficacy of a novel arterial closure device (ACD) in common femoral artery procedures to that of the FDA submitted historical manual pressure control group, who underwent either a diagnostic angiogram (DA) or a percutaneous coronary intervention (PCI) procedure. Methods and Results A total of 55 patients were enrolled in this study of the novel ACD. Of the 55 patients, 39 were enrolled in the DA group and 16 were enrolled in the PCI group. Six patients were excluded. A device was deployed in 49 patients. Time to hemostasis (TTH), time to ambulation (TTA), device function, and device-related vascular complications were measured. In the device group, the TTH for the combined DA and PCI patients was 32 seconds (0.54 ± 0.93 minutes), significantly lower when compared with 16.0 ± 12.2 minutes ( P < 0.0001) for the control group. Overall major vascular complication rate did not differ significantly, device group (1/49) and the historical control group (1/217). TTA in the combined PCI and DA device group was 226.4 ± 231.9 at the German site (site ambulation policy). In the Irish site, the average TTA in the PCI group was 187 minutes (n = 8) and 85 minutes (n = 14) in the DA group. Conclusion The Celt ACD® device is safe, effective, and significantly decreases the TTH compared to manual pressure and has a low vascular complications rate. The device may be effective in early ambulation and discharge of patients postcoronary intervention procedures. [ABSTRACT FROM AUTHOR]

The c-Jun N-terminal kinases (JNKs) are stress-activated serine-threonine kinases that have recently been linked to various neurological disorders. We previously described a patient with intellectual disability (ID) and seizures (Patient 1), carrying a de novo chromosome translocation affecting the CNS-expressed MAPK10/JNK3 gene. Here, we describe a second ID patient (Patient 2) with a similar translocation that likewise truncates MAPK10/JNK3, highlighting a role for JNK3 in human brain development. We have pinpointed the breakpoint in Patient 2, which is just distal to that in Patient 1. In both patients, the rearrangement resulted in a predicted protein interrupted towards the C-terminal end of the kinase domain. We demonstrate that these truncated proteins, although capable of weak interaction with various known JNK scaffolds, are not capable of phosphorylating the classical JNK target c-Jun in vitro, which suggests that the patient phenotype potentially arises from partial loss of JNK3 function. We next investigated JNK3-binding partners to further explore potential disease mechanisms. We identified PSD-95, SAP102 and SHANK3 as novel interaction partners for JNK3, and we demonstrate that JNK3 and PSD-95 exhibit partially overlapping expression at synaptic sites in cultured hippocampal neurons. Moreover, JNK3, like JNK1, is capable of phosphorylating PSD-95 in vitro, whereas disease-associated mutant JNK3 proteins do not. We conclude that reduced JNK3 activity has potentially deleterious effects on neuronal function via altered regulation of a set of post-synaptic proteins. [ABSTRACT FROM AUTHOR]

Purpose: The purposes of this study were to calculate attributable costs of candidemia in patients with severe sepsis and to obtain preliminary data regarding the potential effects of polymerase chain reaction-based pathogen detection on antifungal therapy for these patients. Methods: Patients treated between 2004 and 2010 because of severe sepsis were included into this retrospective analysis. The hospital management provided annual fixed costs per patient-day; data for variable intensive care unit costs were taken from the literature. Multiplex polymerase chain reaction (PCR) was used (VYOO®, SIRS-Lab, Jena, Germany) for pathogen detection in the blood. Results: Thirty-two patients with candidemia were identified. Of 874 patients with sepsis, propensity score matching found 32 corresponding patients with sepsis but without candida infection but similar risk factors for developing candidemia. Attributable costs of candidemia were 7713.79 Euro (cost increase, 19.4%). Initiation of antifungal therapy was reduced from 67.5 (52.4, 90) hours in the group, where candida infection was determined by blood culture, to 31.0 (28.0, 37.5; P b .01) hours after detection by multiplex PCR. Conclusions: Candidemia increases costs of care in patients with septic shock. Polymerase chain reaction-based pathogen detection significantly reduces the time to initiation of antifungal therapy. This might impact on the clinical course of the disease but need to be confirmed in further trials. [ABSTRACT FROM AUTHOR]

Background: Compared with single-incision laparoscopy, multiport laparoscopy is associated with greater risk of postoperative wound pain, infection, incisional hernias, and suboptimal cosmetic outcomes. The feasibility of minimally invasive single-incision laparoscopic surgery (SILS) for colorectal procedures is well-established, but outcome data remain limited. Methods: Patients with benign diverticular disease, Crohn's disease, or ulcerative colitis admitted to Klinikum Leverkusen, Germany, for colonic resection between July 2009 and March 2011 ( n = 224) underwent single-incision laparoscopic surgery using the SILS™ port system. Surgeons had ≥7 years' experience in laparoscopic colon surgery but no SILS™ experience. Patient demographic and clinical data were collected prospectively. Pain was evaluated by using a visual analog scale (0-10). Data were analyzed by using the SPSS PASW Statistics 18 database. Results: The majority of patients underwent sigmoid colectomy with high anterior resection (AR) or left hemicolectomy ( n = 150) for diverticulitis. Our conversion rate to open surgery was 6.3 %, half in patients undergoing sigmoid colectomy with high AR or left hemicolectomy, 95 % of whom had diverticulitis. Mean operating time was 166 ± 74 (range, 40-441) min in the overall population, with shorter times for single-port transanal tumor resection (SPTTR; 89 ± 51 min; range, 40-153 min) and longer times for proctocolectomy (325 min; range, 110-441 min). Mean hospital stay was approximately 10 days, longer after abdominoperineal rectal resection or proctocolectomy (12-16 days). Most complications occurred following sigmoid colectomy with high AR or left hemicolectomy [19/25 (76 %) of early and 4/5 (80 %) of late complications, respectively]. Pain was <4 on a scale of 0-10 in all cases on postoperative day 1, and typically decreased during the next 2 days. Conclusions: Our findings support the feasibility and tolerability of colorectal surgery, conducted by experienced laparoscopic surgeons without specific training in use of the SILS™ port. [ABSTRACT FROM AUTHOR]

Recurrent hepatitis C virus (HCV) infection occurs universally and is regarded as a major cause of mortality after liver transplantation (LT) for HCV-related end-stage liver disease. We conducted this large, single-center, retrospective study to ascertain the long-term impact of virological response to treatment of recurrent hepatitis C on survival of LT recipients. From August 1987 to October 2011, 285 patients have received interferon-based antiviral therapy for recurrent hepatitis C. Of these 285, 245 patients were enrolled in this study. One hundred and twenty-six patients (51.4%) achieved sustained virological response (SVR). Relapsers (undetectable HCV-RNA at end of treatment, becoming positive afterward) comprised 9.0% (22/245), and nonresponse (NR; never achieving undetectable HCV-RNA) 39.6% (97/245). The median follow-up after completion of antiviral treatment was 2081 days. Using Kaplan-Meier method, patients who achieved SVR were shown to have significantly better 5-year patient survival (95.2%) than the NR group (49.9%) ( P < 0.001), and a trend toward better 5-year survival than relapsers (87.5%) ( P = 0.14); relapsers had a significantly longer survival than NR group ( P = 0.005). When compared with NR, SVR and relapse appeared to be significant predictors of better survival, independent of underlying characteristics. In conclusion, virological response, especially SVR, translates into markedly improved long-term patient outcomes in patients transplanted for hepatitis C. [ABSTRACT FROM AUTHOR]

Objectives: Hepatocyte growth factor (HGF) plays an important role in the improvement in cardiac function and remodeling in a variety of cardiovascular diseases. It is also a strong predictor of mortality in some heart failure (HF) patients. However, its prognostic value in patients with Chagas' disease (CD) or idiopathic dilated cardiomyopathy (DCM) remains to be investigated. Methods and Results: In this prospective cohort study, HGF concentrations were measured in patients with CD (n = 91), DCM (n = 47), and control subjects (n = 25). While no difference was detected for patients with New York Heart Association class I-II, HGF was significantly increased in advanced HF patients (New York Heart Association class III-IV) in both CD and DCM groups, compared with healthy subjects. There was a strong correlation between HGF and left ventricular ejection fraction in CD patients. However, there was no correlation in patients with DCM. Despite its strong correlation with left ventricular ejection fraction in CD patients, HGF failed to predict mortality and necessity for heart transplant in both CD and DCM patients. Conclusions: Although HGF can be significantly increased in advanced HF patients with CD and DCM, its prognostic value for endpoints is minor. Therefore, the formerly described predictive power for HGF in HF might be restricted to specific etiologies of HF. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]