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.

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.

Vertebral osteomyelitis in patients with Staphylococcus aureus bloodstream infection: Evaluation of risk factors for treatment failure.

OBJECTIVES: Staphylococcus aureus is the most common cause of pyogenic vertebral osteomyelitis (VO). Studies indicate that S. aureus VO results in poor outcome. We aimed to investigate risk factors for treatment failure in patients with Staphylococcus aureus bloodstream infection (SAB) and VO. METHODS: We conducted a post hoc-analysis of data from a German bi-center prospective SAB cohort (2006-2014). Patients were followed-up for one year. Primary outcome was treatment failure defined as relapse and/or death within one year. RESULTS: A total of 1069 patients with SAB were analyzed, with 92 VO patients. In addition to antibiotic treatment, surgery was performed in 60/92 patients. Treatment failed in 44/92 patients (death, n = 42; relapse, n = 2). Multivariable analysis revealed higher age (HR 1.04 [per year], 95%CI 1.01-1.07), Charlson comorbidity index (HR 1.20, 95%CI 1.06-1.36), presence of neurologic deficits (HR 2.53, 95%CI 1.15-5.53) and local abscess formation (HR 3.35, 95%CI 1.39-8.04) as independent risk factors for treatment failure. In contrast, surgery seemed to be associated with a favourable outcome (HR 0.45 (95%CI 0.20-0.997)). CONCLUSION: SAB patients with VO exhibit a high treatment failure rate. Red flags are older age, comorbidities, neurologic deficits and local abscess formation. Whether these patients benefit from intensified treatment (e.g. radical surgery, prolongation of antibiotics) should be investigated further.

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.

[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.

Diagnostic value of abdominal follow-up sonography in polytrauma patients: A retrospective study.

In many German trauma centres, it is routine to perform abdominal follow-up sonography (AFS) 6 h after admission for patients with multiple trauma, even if the clinical course is uneventful and multi-slice computed tomography (MSCT) reveals no abdominal pathology. However, this approach is not recommended in the German Guidelines for trauma, and recent studies have questioned the value of AFS to these patients. The present study aimed to evaluate the revised German Guidelines for trauma with respect to the omission of AFS.We included patients with multiple injuries with no clinical signs of abdominal trauma and with normal abdominal MSCT. We collected clinical data of 370 consecutive patients who underwent AFS (Group A) and another 370 consecutive patients who did not undergo AFS (Group B).No abdominal injury was missed by the omission of AFS, and thus, no patient suffered from its omission or benefitted from the use of AFS. In our study population, the negative predictive value of normal MSCT results combined with no clinical signs of abdominal trauma was 100% (95% confidence interval: 99.5%-100.0%).This single-centre study conducted in a large German trauma centre demonstrates AFS to have no utility in the diagnosis of abdominal injury. Moreover, omission of AFS for conscious patients without clinical signs of abdominal trauma and with negative abdominal MSCT does not appear to have negative consequences in terms of missed abdominal injury.Therefore, AFS can be safely omitted in the majority of cases of polytrauma, which simplifies the imaging workup tremendously.

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.

Adverse events associated with deep brain stimulation in patients with childhood-onset dystonia.

BACKGROUND: Data on pediatric DBS is still limited because of small numbers in single center series and lack of systematic multi-center trials. OBJECTIVES: We evaluate short- and long-term adverse events (AEs) of patients undergoing deep brain stimulation (DBS) during childhood and adolescence. METHODS: Data collected by the German registry on pediatric DBS (GEPESTIM) were analyzed according to reversible and irreversible AEs and time of occurrence with relation to DBS-surgery: Intraoperative, perioperative (<4 weeks), postoperative (4 weeks < 6 months) and long term AEs (>6 months). RESULTS: 72 patients with childhood-onset dystonia from 10 DBS-centers, who received 173 DBS electrodes and 141 implantable pulse generators (IPG), were included in the registry. Mean time of postoperative follow-up was 4.6 ±â€¯4 years. In total, 184 AEs were documented in 53 patients (73.6%). 52 DBS-related AEs in 26 patients (36.1%) required 45 subsequent surgical interventions 4.7 ±â€¯4.1 years (range 3 months-15 years) after initial implantation. The total risk of an AE requiring surgical intervention was 7.9% per electrode-year. Hardware-related AEs were the most common reason for surgery. There was a tendency of a higher rate of AEs in patients aged 7-9 years beyond 6 months after implantation. DISCUSSION: The intraoperative risk of AEs in pediatric patients with dystonia undergoing DBS is very low, whereas the rate of postoperative hardware-related AEs is a prominent feature with a higher occurrence compared to adults, especially on long-term follow-up. CONCLUSION: Factors leading to such AEs must be identified and patient management has to be focused on risk minimization strategies in order to improve DBS therapy and maximize outcome in pediatric patients.

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.

Patient-centered integrated healthcare improves quality of life in Parkinson's disease patients: a randomized controlled trial.

INTRODUCTION: Improving quality of life (QoL) is a key issue when dealing with Parkinson's disease (PD). Integrative care shows potential to achieve improvements in QoL. Here, we analyzed whether a community-based, open-label, integrated approach improves QoL in PD patients. METHODS: PD patients were screened for eligibility and evaluated by a university-based PD specialist, a PD nurse, and a general neurologist at a local practice. Patients were randomly assigned to a control group (CG), receiving standard German neurological treatment including a baseline assessment and follow-up visit at 6 months, or an interventional group (IG) who received an individually tailored therapy plan and additional home visits. Patients and investigators were not blinded for either intervention. Primary outcome analysis compared the differential change of PDQ-39 from baseline to 6-month follow-up between CG and IG. Between-group changes in mood, motor/non-motor functioning, and cognition were secondary outcomes. RESULTS: 300 patients were included and randomized equally to IG and CG. 132 IG and 125 CG patients had a valid PDQ-39 at follow-up and qualified for the modified ITT analysis. PDQ-39 improved more in IG compared to CG [2.2 points (95% CI - 4.4 to 0.1); p = 0.044]. Likewise, change scores between IG and CG favored IG for UPDRS III (p < 0.001, mean change 3.3, 95% CI - 4.9 to - 1.7) and PD-NMS (p < 0.001, mean change 11.3, 95% CI - 17.1 to - 5.5). CONCLUSIONS: Data show that an integrated approach, compared to regular PD care, improves QoL as well as motor and nonmotor PD symptoms over 6 months. Future studies need to address the cost-benefit ratio and whether positive effects can be maintained beyond intervention.

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.

German registry of paediatric deep brain stimulation in patients with childhood-onset dystonia (GEPESTIM).

BACKGROUND: Data on paediatric deep brain stimulation (DBS) is limited, especially for long-term outcomes, because of small numbers in single center series and lack of systematic multi-center trials. OBJECTIVES: We seek to systematically evaluate the clinical outcome of paediatric patients undergoing DBS. METHODS: A German registry on paediatric DBS (GEPESTIM) was created to collect data of patients with dystonia undergoing DBS up to the age of 18 years. Patients were divided into three groups according to etiology (group 1 inherited, group 2 acquired, and group 3 idiopathic dystonia). RESULTS: Data of 44 patients with a mean age of 12.8 years at time of operation provided by 6 German centers could be documented in the registry so far (group 1 n = 18, group 2 n = 16, group 3 n = 10). Average absolute improvement after implantation was 15.5 ± 18.0 for 27 patients with pre- and postoperative Burke-Fahn-Marsden Dystonia Rating scale movement scores available (p < 0.001) (group 1: 19.6 ± 19.7, n = 12; group 2: 7.0 ± 8.9, n = 8; group 3: 19.2 ± 20.7, n = 7). Infection was the main reason for hardware removal (n = 6). 20 IPG replacements due to battery expiry were necessary in 15 patients at 3.7 ± 1.8 years after last implantation. DISCUSSION: Pre- and postoperative data on paediatric DBS are very heterogeneous and incomplete but corroborate the positive effects of DBS on inherited and acquired dystonia. Adverse events including relatively frequent IPG replacements due to battery expiry seem to be a prominent feature of children with dystonia undergoing DBS. The registry enables collaborative research on DBS treatment in the paediatric population and to create standardized management algorithms in the future.

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.

Combination antimicrobial therapy in patients with Staphylococcus aureus bacteraemia-a post hoc analysis in 964 prospectively evaluated patients.

OBJECTIVES: The evidence for using combination antimicrobial therapy (CoRx) in Staphylococcus aureus bacteraemia (SAB) is limited. We aimed to investigate whether CoRx is associated with higher survival or lower SAB-related late complications. METHODS: We performed a post hoc analysis of a prospective SAB cohort study. CoRx was defined as a cell wall-active antistaphylococcal agent plus either rifampicin, a fluoroquinolone, fosfomycin or an aminoglycoside. To adjust for survivor bias multivariable Cox models that included CoRx as a time-dependent covariable were calculated. RESULTS: Of 964 evaluable patients, 512 (53%) received CoRx, most of them (301/512, 59%) rifampicin-containing CoRx. All-cause mortality after 30 and 90 days was similar for the two groups, although the patients in the CoRx group had more often endocarditis, deep-seated or disseminated infections and severe sepsis/septic shock. For the entire cohort, only age, comorbidity and severe sepsis/septic shock were associated with a higher mortality and infectious disease consultation, but not CoRx with a lower mortality. However, in the subgroup of patients with implanted foreign bodies or devices CoRx was independently associated with a lower mortality at 30 days (hazard ratio 0.6, 95% confidence interval 0.3-1.1) and at 90 days (hazard ratio 0.6, 95% confidence interval 0.4-0.9). SAB-related late complications in this subgroup occurred in 15 (10.6%) of 142 patients in the monotherapy group vs. nine (4.5%) of 202 patients in the CoRx group (p 0.03). CONCLUSIONS: In a setting of optimized management of adult patients with SAB secured by infectious disease consultations, this observational study could not prove CoRx to be independently associated with improved survival or reduced late complications in the entire cohort. However, administration of CoRx may be associated with lower mortality and fewer SAB-related late complications in the subgroup of patients with implanted foreign bodies or devices. Prospective randomized trials should be performed to prove this benefit.

Postoperative Continuous Infusion of Local Anesthesia in Hand-Assisted Retroperitoneoscopic Living Donor Nephrectomy.

INTRODUCTION: Postoperative pain management in living kidney donor nephrectomy plays a key role in donor comfort and is important for the further acceptance of living kidney donation in times of organ shortage. Standard pain treatment (SPT) based on opioids is limited due to related side effects. Continuous infusion of local anesthesia (CILA) into the operative field is a promising alternative. The aim of this study was to evaluate whether CILA could reduce the dose of opioids in living kidney donors operated with hand-assisted retroperitoneoscopic donor nephrectomy (HARP). METHODS: An observational study on 30 living donors was performed. The primary outcome was the difference of morphine equivalents (MEQ) administered between CILA and SPT. RESULTS: On day 0 and 1, living donors with CILA received significant less MEQ compared to the SPT group, although on day 1 this effect was not statistically significant (day 0: 6.3 mg, interquartile range [IR] 4.2-11.2 vs 16.8 mg, IR 10.5-22.1, P = .009; day 1: 5.25 mg, IR 2.1-13.3 vs 13.3 mg, IR 6.7-23.8, P = .150). On days 2 and 3 there was no difference (day 2: 13.3 mg, IR 0.0-20.0 vs 13.3 mg, IR 6.7-13.3, P = .708; day 3: 13.3 mg, IR 0.0-26.7 vs 13.3 mg, IR 6.7-20, P = .825). Overall (days 0 to3) MEQ was also less for CILA without reaching statistical significance (39.6 mg, IR 10.9-70.5 vs 59.6 mg, IR 42.4-72.9, P = .187). CONCLUSIONS: CILA seems to be an effective instrument for donor pain management in the first 24 hours after HARP. Its effect abates by 48 hours after surgery, especially if highly potent nonopioids are given.

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).

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.