The influence of persistent bleeding after supracervical hysterectomy on depressive and anxious symptoms: a prospective bicenter study.

PURPOSE: Postoperative spotting is a frequent adverse symptom after laparoscopic supracervical hysterectomy (LSH). The conical excision (eLSH) reduces the postoperative spotting rate, but data in a larger collective are still rare and inconsistent. The influence of persistent bleeding on the anxious and depressive symptoms has not been analyzed yet. METHODS: 311 patients, who underwent a laparoscopic supracervical hysterectomy with conical excision (n = 163), or with straight cervical resection (n = 148) were included. Anxious and depressive symptoms and postoperative spotting were recorded before operation, at 3 month follow-up and at 1 year follow-up in both operative groups using a validated questionnaire (German version of Hospital Anxiety and Depression Scale, HADS-D) and additional questions concerning the frequency and impact of bleeding. Statistical analysis included the impairment of bleeding as well as its impact on depressive and anxious symptoms for both groups. RESULTS: 11.5% after eLSH and 15.5% after LSH reported spotting after 1 year. Supracervical hysterectomy significantly improves depressive and anxious symptoms at 3 and at 12 month follow-up for both groups (p < 0.001) independent on residual spotting. Patients with a preoperative continuous bleeding showed a maximum benefit independent on operative method. CONCLUSION: Laparoscopic supracervical hysterectomy has a positive effect on anxious and depressive symptoms in the short-term and intermediate-term follow-up. The conical excision of the cervical stump reduces postoperative spotting rate, but has no explicit advantage on symptoms of depression or anxiety, irrespective of residual postoperative spotting.

The influence of conventional and extended supracervical hysterectomy on sexuality and quality of life parameters: a prospective bi-center study with a special focus on postoperative spotting.

PURPOSE: Supracervical as well as total hysterectomy are considered to improve postoperative sexuality as well as quality of life, but the benefit of supracervical hysterectomy (LSH) is impaired in up to 20 percent by postoperative spotting. The aim of this study was to analyze the influence of a conical excision of the cervical stump during supracervical hysterectomy on the postoperative spotting rate and its influence on sexuality and in turn quality of life. METHODS: 321 Patients who underwent a laparoscopic supracervical hysterectomy with conical excision (extended laparoscopic supracervical hysterectomy, eLSH, n = 166, Dormagen hospital) or with straight cervical resection (laparoscopic supracervical hysterectomy, LSH, n = 133, MIC Clinics Berlin) were included. Sexual matters, quality of life parameters and additional questions were recorded before operation, at three months of follow up, and at one year of follow up in both groups using a validated questionnaire (German version of International Consultation on Incontinence Questionnaire Vaginal Symptoms Module, ICIQ_VS). Statistical analysis included the impact and impairment of bleeding on sexuality, quality of life in both groups and co-factors such as vaginal symptoms. RESULTS: 11.3% after eLSH and 15.5% after LSH reported spotting after 1 year. Supracervical hysterectomy significantly improves quality of life and sexuality and a conical excision of the remaining stump is associated with a lower but insignificantly reduced spotting rates. Postoperative spotting has no negative influence on sexual matter score of ICIQ_VS, but reduces the postoperative quality of life focusing on vaginal symptoms in a significant way. CONCLUSION: The improvement of ICIQ_VS scores after supracervical hysterectomy is independent of postoperative spotting, but the quality-of-life score is positively influenced by a reduction in the postoperative spotting rate.

[Perception of the COVID-19 Pandemic among Pneumology Professionals in Germany]. / Wahrnehmung der COVID-19-Pandemie unter pneumologischen Fachkräften in Deutschland.

The COVID-19 pandemic represents a huge burden on global health systems. Although far-reaching prevention measures such as the increase of intensive care capacities and drastic restrictions of public life have so far been able to avert an overload of the German health care system, the current situation implies an exceptionally high burden on medical professionals. The current study presents the results of an opinion evaluation among 513 pneumology specialists in Germany in the period from March 27th to April 11th, 2020. While the majority of respondents stated that Germany was "well" prepared for the pandemic, this assessment was significantly worse among participants from the outpatient sector compared to the hospital sector (p < 0.001). Furthermore, a lack of medical protective equipment was reported significantly more frequently by respondents from the outpatient sector (p < 0.001). The importance of telemedicine approaches during the COVID-19 pandemic was rated "high" (35.2 %) or "very high" (17.2 %) by most pneumology professionals, with participants from the hospital sector giving a higher rating (p < 0.001). Finally, 45.8 % of the respondents expressed a "negative" influence of the COVID-19 pandemic on their personal mood and 58.3 % expressed "strong" or "very strong" concerns about the health of their fellow human beings. This assessment was significantly stronger among female participants and participants from the nursing sector (p < 0.001). In summary, the current study analyses for the first time the professional and personal impact of the COVID-19 pandemic on pneumology professionals in Germany. The results could help to identify first starting points to better support health professionals during the current and future challenges.

Cognitive and emotional empathy in individuals at clinical high risk of psychosis.

BACKGROUND: Impairments of social cognition are considered core features of schizophrenia and are established predictors of social functioning. However, affective aspects of social cognition including empathy have far less been studied than its cognitive dimensions. The role of empathy in the development of schizophrenia remains largely elusive. METHODS: Emotional and cognitive empathy were investigated in large sample of 120 individuals at Clinical High Risk of Psychosis (CHR-P) and compared with 50 patients with schizophrenia and 50 healthy controls. A behavioral empathy assessment, the Multifaceted Empathy Test, was implemented, and associations of empathy with cognition, social functioning, and symptoms were determined. RESULTS: Our findings demonstrated significant reductions of emotional empathy in individuals at CHR-P, while cognitive empathy appeared intact. Only individuals with schizophrenia showed significantly reduced scores of cognitive empathy compared to healthy controls and individuals at CHR-P. Individuals at CHR-P were characterized by significantly lower scores of emotional empathy and unspecific arousal for both positive and negative affective valences compared to matched healthy controls and patients with schizophrenia. Results also indicated a correlation of lower scores of emotional empathy and arousal with higher scores of prodromal symptoms. CONCLUSION: Findings suggest that the tendency to 'feel with' an interaction partner is reduced in individuals at CHR-P. Altered emotional reactivity may represent an additional, early vulnerability marker, even if cognitive mentalizing is grossly unimpaired in the prodromal stage. Different mechanisms might contribute to reductions of cognitive and emotional empathy in different stages of non-affective psychotic disorders and should be further explored.

PCR based detection of tcdCΔ117 in Clostridium difficile infection identifies patients at risk for recurrence - A hospital-based prospective observational study.

OBJECTIVES: Increasing incidence and severity of Clostridium difficile infection (CDI) in the last decades has been attributed to the emergence of hypervirulent C. difficile strain PCR-ribotype 027 (RT027). Commercial multiplex real-time PCR tests allow the presumptive identification of RT027 by detecting a single-base deletion at nt117 in the tcdC gene (tcdCΔ117). The clinical usefulness of the detection of tcdCΔ117 is unclear. Therefore, we evaluated test performance and clinical association of the detection of tcdCΔ117 in patients with CDI in a prospective observational study conducted in a tertiary care hospital in Germany. METHODS: From June to October 2015, stool from all patients with suspected CDI was tested for C. difficile according to ESCMID guidelines. C. difficile was cultured from positive samples and ribotyping was performed. Clinical data were collected prospectively from all C. difficile positive patients. RESULTS: From 1121 tested stool samples 107 patients with CDI were included in the study. TcdCΔ117 was detected in 18 (16.8%) of these patients. Multivariable logistic regression analysis revealed an independent association of detection of tcdCΔ117 with a further episode of CDI (OR 14.6; 95% CI 3.6-58.3; p < 0.001) and death within 30 days of the positive test (OR 5.1; 95% CI 1.0-25.7; p = 0.046). As follow up data are limited, it remains unclear, whether the further episode of CDI was due to tcdCΔ117 (recurrence) or another type. CONCLUSION: In our setting, PCR-based detection of tcdCΔ117 identified patients at risk for recurrent CDI and increased mortality and thus may guide therapeutic choices in CDI patients at the time of diagnosis.

Hyposalivation and xerostomia among Parkinson's disease patients and its impact on quality of life.

OBJECTIVE: Parkinson's disease (PD) adversely affects oral health (OH). However, the informative value of xerostomia compared to objective parameters and its impact on quality of life (QoL) are still unclear. This study aimed to explore whether xerostomia correlates with hyposalivation and to define its impact on OH-related QoL. MATERIALS AND METHODS: Whole stimulated saliva (WSS) was collected from 30 patients with PD and 30 matched healthy controls. Objective parameters (community periodontal index of treatment needs, plaque/gingivitis index, mucosa situation and cheilitis angularis) and questionnaires (German Oral Health Impact Profile [OHIPG]-14, visual analogue scale [VAS], xerostomia [yes/no] and the Unified Parkinson's Disease Rating Scale-II) were assessed. RESULTS: Eighty-seven per cent of patients with PD showed hyposalivation vs 50% of controls (P = 0.001); 50% of patients with PD reported xerostomia, and none of controls (P < 0.001). The OHIPG-14 was impaired in patients with PD compared to controls (P < 0.001), PD patients with xerostomia reported mean VAS values of 4.1 (s.d.: 2.2). WSS did not correlate with VAS values. CONCLUSIONS: Half of the patients with PD reported xerostomia and underestimated their xerostomic status, with higher probability than healthy controls. WSS did not reflect the grade of xerostomia. Patients with PD suffered from impaired OH-related QoL. Dental teams should not overlook these oral health risks.

The effect of neuromuscular blockade on the efficiency of facemask ventilation in patients difficult to facemask ventilate: a prospective trial.

Facemask ventilation of the lungs can be an important rescue intervention in a 'cannot intubate' scenario. We assessed the effect of neuromuscular blockade on expiratory tidal volumes in patients with expected difficulty in mask ventilation. The lungs of patients with at least three predictors of difficulty in mask ventilation were ventilated using a facemask held with two hands, with mechanical ventilation set in a pressure-controlled mode. Tidal volumes were recorded before and after the establishment of complete neuromuscular block. In 113 patients, median (IQR [range]) tidal volume increased from 350 (260-492 [80-850]) ml initially, by 48% to 517 (373-667 [100-1250]) ml 30 s after rocuronium administration, (p < 0.001). After the onset of the complete neuromuscular block, a median tidal volume of 600 (433-750 [250-1303]) ml was observed, corresponding to an increase of 71% from baseline values (p < 0.001), and 16% from values obtained 30 s after rocuronium administration, respectively; p = 0.003). No decrease in the tidal volume during the measurements was observed. We conclude that the administration of rocuronium at a dose of 0.6 mg.kg-1 was able to improve facemask ventilation in all cases with a potentially clinically relevant increase in tidal volume. The early use of a neuromuscular blocking agent can be considered as a therapeutic option in case of difficulty with mask ventilation.

A randomized trial on chlorhexidine dressings for the prevention of catheter-related bloodstream infections in neutropenic patients.

BACKGROUND: Central venous catheter (CVC)-related bloodstream infections (CRBSI) are a frequent cause of morbidity and mortality in patients with chemotherapy-induced neutropenia. Chlorhexidine containing catheter securement dressings may prevent CRBSI. PATIENTS AND METHODS: A multicenter randomized, controlled trial was conducted at 10 German hematology departments. We compared chlorhexidine-containing dressings with non-chlorhexidine control dressings in neutropenic patients. The primary end point was the incidence of definite CRBSI within the first 14 days (dCRBSI14) of CVC placement. Secondary end points included combined incidence of definite or probable CRBSI within 14 days (dpCRBSI14), overall (dpCRBSI), incidence of unscheduled dressing changes and adverse events. RESULTS: From February 2012 to September 2014, 613 assessable patients were included in the study. The incidence of dCRBSI14 was 2.6% (8/307) in the chlorhexidine and 3.9% (12/306) in the control group (P = 0.375). Both dpCRBSI14 and dpCRBSI were significantly less frequent in the study group with dpCRBSI14 in 6.5% (20/307) of the chlorhexidine group when compared with 11% (34/306) in the control group (P = 0.047), and dpCRBSI in 10.4% (32/307) versus 17% (52/306), respectively (P = 0.019). The frequency of dressing intolerance with cutaneous and soft tissue abnormalities at the contact area was similar in both groups (12.4% and 11.8%; P = 0.901). CONCLUSIONS: Although the trial failed its primary end point, the application of chlorhexidine containing catheter securement dressings reduces the incidence of definite or probable CRBSI in neutropenic patients. CLINICAL TRIALS NUMBER: NCT01544686 (Clinicaltrials.gov).

Circulating annexin A5 predicts mortality in patients with heart failure.

BACKGROUND: Natriuretic peptides are currently used to predict mortality in patients with heart failure (HF). However, novel independent biomarkers are needed to improve risk stratification in these patients. We hypothesized that annexin A5 (anxA5) would be highly expressed by organs which are generally affected by HF and that circulating anxA5 levels would predict mortality in HF patients. METHODS: We prospectively determined the diagnostic value of anxA5, N-terminal pro-B-type natriuretic peptide (NT-proBNP), C-reactive protein (CRP) and estimated glomerular filtration rate (eGFR) to predict mortality in 180 HF patients during a median follow-up of 3.6 years. Studies were conducted with anxA5(-/-) mice to investigate the underlying mechanisms. RESULTS: AnxA5 levels were significantly elevated in HF patients compared to healthy control subjects. Cox regression analysis demonstrated that anxA5, NT-proBNP and eGFR all predict mortality independently. AnxA5 significantly improved the diagnostic efficiency of NT-proBNP alone (improvement of c-statistic from 0.662 to 0.705, P < 0.001) and also combined with eGFR and CRP (improvement of c-statistic from 0.675 to 0.738, P < 0.001) to predict mortality in the Cox regression model. Receiver operating characteristic curve analysis showed that anxA5 predicted 3-year survival (area under curve 0.708) with an optimal cut-off value of 2.24 ng mL(-1) . Using anxA5(-/-) mice, we demonstrated that anxA5 is highly expressed in organs that are often affected by HF including lung, kidney, liver and spleen. Lysis of these organs in vitro resulted in a marked and significant increase in anxA5 concentrations. CONCLUSION: AnxA5 improves the diagnostic efficiency of conventional biomarkers to predict mortality in HF patients. Whereas natriuretic peptides originate from the myocardium, high circulating anxA5 levels in patients with HF are likely to reflect peripheral organ damage secondary to HF.

Deep brain stimulation of the nucleus basalis of Meynert in Alzheimer's dementia.

Cholinergic neurons of the medial forebrain are considered important contributors to brain plasticity and neuromodulation. A reduction of cholinergic innervation can lead to pathophysiological changes of neurotransmission and is observed in Alzheimer's disease. Here we report on six patients with mild to moderate Alzheimer's disease (AD) treated with bilateral low-frequency deep brain stimulation (DBS) of the nucleus basalis of Meynert (NBM). During a four-week double-blind sham-controlled phase and a subsequent 11-month follow-up open label period, clinical outcome was assessed by neuropsychological examination using the Alzheimer's Disease Assessment Scale-cognitive subscale as the primary outcome measure. Electroencephalography and [(18)F]-fluoro-desoxyglucose positron emission tomography were, besides others, secondary endpoints. On the basis of stable or improved primary outcome parameters twelve months after surgery, four of the six patients were considered responders. No severe or non-transitional side effects related to the stimulation were observed. Taking into account all limitations of a pilot study, we conclude that DBS of the NBM is both technically feasible and well tolerated.

Asymptomatic anal sexually transmitted infections in HIV-positive men attending anal cancer screening.

BACKGROUND: HIV-positive men who have sex with men (HIV+MSM) have an increased risk for anal dysplasia and for sexually transmitted infections (STIs). OBJECTIVES: We determined the positivity rates of Chlamydia trachomatis (CT), Neisseria gonorrhoea (NG), Mycoplasma genitalium (MG) and syphilis in HIV+MSM participating in an anal cancer screening programme. METHODS: In total, 852 intra-anal swabs were collected from 503 HIV+MSM between 2012 and 2014. Anal cytology and polymerase chain reaction assays for human papillomavirus (HPV), CT, NG and MG detection were performed. The syphilis status was determined serologically. Risk factors for STIs were explored by multiple logistic regression analysis. RESULTS: In total 20·7% (104 of 503) of the patients had an STI other than HPV within the study period. The most common was CT, found in 10·9%, followed by NG (8·9%) and MG (4·2%). Early syphilis was detected in 4·6% and past syphilis in 44·5% of the HIV+MSM. Eighteen patients (3·6%) had more than one STI episode, and 90·6% of the 127 cases of STIs were asymptomatic. Age, anal HPV infection, abnormal anal cytology and previous syphilis were risk factors for STI. CONCLUSIONS: Anal STIs are frequent and mostly asymptomatic in HIV+MSM participating in anal cancer screening. STI screening should be incorporated into anal cancer screening programmes for HIV+MSM.

Outcome of empirical or targeted antifungal therapy after antifungal prophylaxis in febrile neutropenia.

Azole prophylaxis has been shown to be effective in preventing invasive fungal infections (IFIs) and increasing survival in patients with prolonged neutropenia after myelosuppressive chemotherapy for haematological malignancies. Similarly, empirical antifungal therapy for persistent neutropenic fever has been shown to reduce IFI-related mortality. However, to date, there is little information with regard to the outcome of patients who receive both strategies. Here, we present our retrospective data on three cohorts of patients receiving empirical or targeted antifungal therapy after different antifungal prophylaxis regimens. All records from patients who received myelosuppressive induction chemotherapy for acute myelogenous leukemia (AML) in our centre from 2004-2010 were analysed. From 2004-2006, itraconazole was used as antifungal prophylaxis; for the first 6 months in 2007, local polyenes and from mid-2007 till 2010, posaconazole. Data of 315 courses of chemotherapy in 211 patients were analysed. Antifungal therapy (empirical or targeted, time point and antifungal agent at the physician's discretion) was initiated in 50/174 (29 %), 7/18 (39 %) and 34/123 courses (28 %, p = 0.615) in the itra cohort, the cohort without systemic prophylaxis and the posa cohort, respectively, and was effective in 24/50 (48 %), 5/7 (71 %) and 22/34 courses (65 %, p = 0.221), respectively. IFI occurred in 25/174 (14 %), 4/18 (22 %) and 16/123 (13 %) courses, respectively (p = 0.580). IFI-related survival was not different in the three cohorts. Antifungal treatment in patients with AML who received azole prophylaxis resulted in the expected efficacy-importantly, prior posaconazole prophylaxis did not render subsequent antifungal treatment less effective than prior itraconazole prophylaxis.

[The use and benefit of the 'children with special health care needs screener' in the paediatric school entrance examinations 2004/2005 in Cologne]. / Einsatz und Nutzen des "Children with Special Health Care Needs-Screener" im Rahmen der Schuleingangsuntersuchung 2004/2005 in Köln.

The aim of this study was to provide an assessment of the usefulness of the questionnaire "Children with Special Health Care Needs Screener" (CSHCN Screener) as a screening instrument to identify children with special needs in the context of paediatric school entrance examinations (SEE).In a retrospective cross-sectional study of the years 2004 and 2005 in Cologne, Germany, the sum variables were derived from the results of the SEE in accordance to the 7 questions of the CSHCN Screener. The correlations of the SEE sum variables and the CSHCN Screener results were analysed and tested for correlations with sociodemographic factors.Of the 18 402 children of the cohorts 2004/2005, corresponding SEE findings and results of the CSHCN Screener were available for 13 076 children. The prevalence of children with special needs was only 6% according to the results of the CSHCN Screener. According to the SEE, however, 26% of the children showed diseases or developmental problems. Out of this group, only one in 8 children was identified by the CSHCN Screener (sensitivity 13%). The sensitivity of the screener was also 13% for children who had been diagnosed to be in need of special support by school physicians. In the case of girls and of children with migration family backgrounds, the sensitivity of the screener was even lower. The CSHCN Screener also could not detect the higher rate of special needs determined by school physicians in children from areas with high quotas of state family support payments.The results of the CSHCN Screener are not convincing, due to his low sensitivity. This is true with regard to its use as a diagnostic tool for the individual child at the beginning of school age as well for its use as an instrument to assess an increased need for support in cohorts of school entry students.

Endurance training alters skeletal muscle MCT contents in T2DM men.

Patients suffering from type 2 diabetes mellitus (T2DM) often exhibit chronic elevated lactate levels which can promote peripheral insulin resistance by disturbing skeletal muscle insulin-signaling. Monocarboxylate transporter (MCT) proteins transfer lactate molecules through cellular membranes. MCT-1 and MCT-4 are the main protein isoforms expressed in human skeletal muscle, with MCT-1 showing a higher affinity (lower Km) for lactate than MCT-4. T2DM patients have reduced membranous MCT-1 proteins. Consequently, the lactate transport between muscle cells and the circulation as well as within an intracellular lactate shuttle, involving mitochondria (where lactate can be further metabolized), can be negatively affected. This study investigates whether moderate cycling endurance training (3 times per week for 3 months) can change skele-tal muscle MCT contents in T2DM men (n=8, years=56±9, body mass index (BMI)=32±4 kg/m(2)). Protein content analyses (immuno-histochemical stainings) were performed in bio-psies taken from the vastus lateralis muscle. Intracellular MCT-1 proteins were up-regulated (relative increase+89%), while intracellular MCT-4 contents were down-regulated (relative decrease - 41%) following endurance training. Sarcolemmal MCT-1 and MCT-4 did not change. The question of whether the training-induced up-regulation of intracellular MCT-1 leads to an improved lactate transport (and clearance) in T2DM patients requires further research.

Rhinomanometric reference intervals for normal total nasal airflow resistance.

BACKGROUND: Reference intervals (RIs) or mean values for normal total nasal airflow resistance are essential for the diagnosis of nasal obstruction. Data relating to nasal airflow are not standardised, and valid and reliable RIs do not exist for the time being. This meta-analysis aimed to determine such "standard" 95%-RIs. METHODOLOGY: Research of related literature listed in Medline, Embase, Cochrane, and Web of Science databases. RESULTS: Airflow resistance data were gathered from 38 studies using active anterior rhinomanometry at a differential pressure of 150Pa to examine patients under congested and decongested mucosal conditions. In the meta-analysis overall values and RIs for normal total nasal airflow resistance under congested nasal mucosal conditions were calculated for all subjects at 0.25Pa/cm3/s (95%-RI 0.10-0.40Pa/cm3/s), adults regardless of gender at 0.25Pa/cm3/s (95%-RI 0.12-0.38Pa/cm3/s), men at 0.24Pa/cm3/s (95%-RI 0.09-0.39Pa/cm3/s), and women at 0.26Pa/cm3/s (95%-RI 0.08-0.44Pa/cm3/s). Asian, African and Caucasian ethnic groups exhibited rising airflow resistance mean values: 0.23Pa/cm3/s (95%-RI 0.08-0.39Pa/cm3/s), 0.25Pa/cm3/s (95%-RI 0.11-0.38Pa/cm3/s) and 0.26Pa/cm3/s (95%-RI 0.13-0.38Pa/cm3/s), respectively. Lower overall mean values resulted under decongested nasal mucosal conditions. CONCLUSION: The reference intervals and mean values ascertained in this meta-analysis improve the diagnosis of nasal obstruction and may represent a useful supplement in existing guidelines for the standardisation of rhinomanometric measurements.

Overall survival and central nervous system activity of crizotinib in ROS1-rearranged lung cancer-final results of the EUCROSS trial.

BACKGROUND: In 2019, we reported the first efficacy and safety analysis of EUCROSS, a phase II trial investigating crizotinib in ROS1 fusion-positive lung cancer. At that time, overall survival (OS) was immature and the effect of crizotinib on intracranial disease control remained unclear. Here, we present the final analysis of OS, systemic and intracranial activity, and the impact of co-occurring aberrations. MATERIALS AND METHODS: EUCROSS was a prospective, single-arm, phase II trial. The primary endpoint was best overall response rate (ORR) using RECIST 1.1. Secondary and exploratory endpoints were progression-free survival (PFS), OS, and efficacy in pre-defined subgroups. RESULTS: Median OS of the intention-to-treat population (N = 34) was 54.8 months [95% confidence interval (CI) 20.3 months-not reached (NR); median follow-up 81.4 months] and median all-cause PFS of the response-evaluable population (N = 30) was 19.4 months (95% CI 10.1-32.2 months). Time on treatment was significantly correlated with OS (R = 0.82; P < 0.0001). Patients with co-occurring TP53 aberrations (28%) had a significantly shorter OS [hazard ratio (HR) 11; 95% CI 2.0-56.0; P = 0.006] and all-cause PFS (HR 4.2; 95% CI 1.2-15; P = 0.025). Patients with central nervous system (CNS) involvement at baseline (N = 6; 20%) had a numerically shorter median OS and all-cause PFS. Median intracranial PFS was 32.2 months (95% CI 23.7 months-NR) and the rate of isolated CNS progression was 24%. CONCLUSIONS: Our final analysis proves the efficacy of crizotinib in ROS1-positive lung cancer, but also highlights the devastating impact of TP53 mutations on survival and treatment efficacy. Additionally, our data show that CNS disease control is durable and the risk of CNS progression while on crizotinib treatment is low.

Delay in the administration of appropriate antimicrobial therapy in Staphylococcus aureus bloodstream infection: a prospective multicenter hospital-based cohort study.

OBJECTIVES: Early broad-spectrum antimicrobial treatment reduces mortality in patients with septic shock. In a multicenter, prospective observational study, we explored whether delayed appropriate antimicrobial therapy (AAT) influences outcome in Staphylococcus aureus bloodstream infection (SAB). METHODS: Two hundred and fifty-six patients with SAB from ten German study centers were enrolled and followed for 3 months. Predisposing factors, clinical features, diagnostic procedures, antimicrobial therapy, and outcome were recorded. The appropriateness of antimicrobial therapy was judged by a trained physician based on in vitro activity, dosage, and duration of therapy. Therapy was considered to be delayed when more than 24 h elapsed between the first positive blood culture and the start of appropriate therapy. The association of delayed therapy with overall mortality and SAB-related events (i.e., attributable mortality or late SAB-related complications) was assessed by crosstabulation and propensity score-based logistic regression. RESULTS: One hundred and sixty-eight patients received AAT during their hospital stay, of whom 42 (25%) received delayed AAT. The overall mortality and the occurrence of severe sepsis or septic shock were lower in patients with delayed AAT, pointing towards confounding by indication. Adjusted 90-day mortality (adjusted odds ratio [OR] 0.91, 95% confidence interval [CI] [0.39-2.13], p 0.82) and SAB-related events (adjusted OR 1.46, 95% CI [0.47-4.51], p 0.52) also failed to show a significant impact of delayed AAT on outcome. CONCLUSION: In patients with SAB, early AAT may not improve survival. However, confounding by indication is a major challenge when analyzing and interpreting observational studies on the impact of delayed AAT.

NT-pro-BNP predicts worsening renal function in patients with chronic systolic heart failure.

BACKGROUND: Worsening renal function (WRF) is frequently observed in patients with heart failure and is associated with worse outcome. The aim of this study was to examine the association of the cardiac serum marker N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) and WRF. METHODS: A total of 125 consecutive patients of a tertiary care outpatient clinic for heart failure prospectively underwent evaluation of renal function every 6 months. The association of baseline NT-pro-BNP with WRF was analysed during a follow up of 18 months. RESULTS: Twenty-eight (22.4%) patients developed WRF (increase in serum creatinine ≥0.3 mg/dL). Patients with WRF (2870 pg/mL, interquartile range (IQR) 1063-4765) had significantly higher baseline NT-pro-BNP values than patients without WRF (547 pg/mL, IQR 173-1454). The risk for WRF increased by 4.0 (95% CI 2.1-7.5) for each standard deviation of log NT-pro-BNP. In multivariable analysis including age, baseline renal function, ejection fraction, New York Heart Association class and diuretic dose, only NT-pro-BNP and diabetes were independent predictors of WRF. At a cut-off level of 696 pg/mL, NT-pro-BNP showed a sensitivity of 92.9% and a negative predictive value of 96.4% for WRF. CONCLUSION: NT-pro-BNP is a strong independent predictor of WRF within 18 months in patients with systolic heart failure with a high negative predictive value. Further studies are needed to evaluate reno-protective strategies in patients with elevated NT-pro-BNP.

Brief Report: Social Anxiety in Autism Spectrum Disorder is Based on Deficits in Social Competence.

This study differentially examined the relation between two clinical constructs: "social anxiety" and "social competence" in autism spectrum disorder (ASD). Employing two questionnaires (SASKO; IU), individuals with ASD (n = 23) showed increased scores of SOCIAL ANXIETY (SASKO) and of INTOLERANCE OF UNCERTAINTY (IU), compared to a non-clinical comparison group (NC; n = 25). SOCIAL ANXIETY scores were equally increased for ASD and a reference population of individuals with social anxiety disorder (SAD; n = 68). However, results showed increased SOCIAL COMPETENCE DEFICITS in ASD compared to SAD and NC groups. This study allows drawing the conclusion that social anxiety symptoms in ASD can be traced back to autism-specific deficits in social skills and are therefore putatively based on different, substantially "deeper" implemented cognitive mechanisms.