[Management of Adult Community-Acquired Pneumonia and Prevention - Update 2021 - Guideline of the German Respiratory Society (DGP), the Paul-Ehrlich-Society for Chemotherapy (PEG), the German Society for Infectious Diseases (DGI), the German Society of Medical Intensive Care and Emergency Medicine (DGIIN), the German Viological Society (DGV), the Competence Network CAPNETZ, the German College of General Practitioneers and Family Physicians (DEGAM), the German Society for Geriatric Medicine (DGG), the German Palliative Society (DGP), the Austrian Society of Pneumology Society (ÖGP), the Austrian Society for Infectious and Tropical Diseases (ÖGIT), the Swiss Respiratory Society (SGP) and the Swiss Society for Infectious Diseases Society (SSI)]. / Behandlung von erwachsenen Patienten mit ambulant erworbener Pneumonie ­ Update 2021.

The present guideline provides a new and updated concept of the management of adult patients with community-acquired pneumonia. It replaces the previous guideline dating from 2016.The guideline was worked out and agreed on following the standards of methodology of a S3-guideline. This includes a systematic literature search and grading, a structured discussion of recommendations supported by the literature as well as the declaration and assessment of potential conflicts of interests.The guideline has a focus on specific clinical circumstances, an update on severity assessment, and includes recommendations for an individualized selection of antimicrobial treatment.The recommendations aim at the same time at a structured assessment of risk for adverse outcome as well as an early determination of treatment goals in order to reduce mortality in patients with curative treatment goal and to provide palliation for patients with treatment restrictions.

[The interdisciplinary orthogeriatric ward round : Recommendations for the clinical routine]. / Die interdisziplinäre alterstraumatologische Visite : Empfehlungen für den Klinikalltag.

BACKGROUND: An orthogeriatric co-management can improve the quality of care for geriatric trauma patients. OBJECTIVE: The aim of this study was the establishment of treatment recommendations for the clinical routine in order to improve the quality of care for geriatric trauma patients. MATERIAL AND METHODS: Over a period of 7 months, 226 patients were discussed and visited once a week on 29 defined days, taking into account current laboratory results, vital signs, the medication as well as the clinical assessment by the nursing personnel. Besides physicians of different medical specialties (trauma surgery, geriatrics, clinical pharmacology, microbiology), members of the nursing staff and case managers took part in the ward rounds. RESULTS: On average, three treatment recommendations were made per patient visit (two pharmacological and one non-pharmacological recommendation [e.g. concerning fluid and delirium management]). The pharmacological and non-pharmacological recommendations were divided into several subcategories. The most frequent pharmacological recommendation was the discontinuation of a drug (30.4% of all pharmacological recommendations). CONCLUSION: The pharmacotherapy of geriatric patients requires careful consideration of contraindications, adverse drug reactions, duplicate medications, circadian aspects, and renal function. Regular re-evaluation of medical equipment can prevent catheter-associated infections. Identification and management of postoperative delirium is an integral component of the interdisciplinary orthogeriatric ward round. Evaluation of anti-infective treatment regimens with the expertise of a microbiologist/infectiologist proved to be very beneficial.

[Nontuberculous mycobacteria in sputum : Recommendations for diagnosis and treatment]. / Nichttuberkulöse Mykobakterien im Sputum : Empfehlungen zu Diagnose und Therapie.

Pulmonary diseases caused by nontuberculous mycobacteria (NTM) have increased over the last years and decades in Germany and also worldwide. Because the disease is more frequent in patients with immunodeficiencies and chronic respiratory diseases, e.g. bronchiectasis, advanced chronic obstructive lung disease (COPD) and cystic fibrosis (CF), an infection with mycobacteria should always be considered in this patient group. The detection in sputum alone is not an indication for treatment but the correct diagnosis should be based on the appropriate clinical symptoms as well as radiological and microbiological criteria. The diagnosis is often delayed because the symptoms are unspecific. The treatment of pulmonary NTM disease is difficult and tedious and for these reasons is often prematurely terminated. Adherence of treating physicians to the guidelines is also conspicuously low. Before starting treatment, it is important to carefully define the goals and clarify the risks and benefits of the treatment with the patient. As adverse toxic events can occur during treatment, it should be closely monitored. In the case of an infrequent pathogen or a severe course of the disease, referral to an NTM specialist center should be undertaken.

Outcomes following autologous hematopoietic stem cell transplant for patients with relapsed Wilms' tumor: a CIBMTR retrospective analysis.

Despite the marked improvement in the overall survival (OS) for patients diagnosed with Wilms' tumor (WT), the outcomes for those who experience relapse have remained disappointing. We describe the outcomes of 253 patients with relapsed WT who received high-dose chemotherapy (HDT) followed by autologous hematopoietic stem cell transplant (HCT) between 1990 and 2013, and were reported to the Center for International Blood and Marrow Transplantation Research. The 5-year estimates for event-free survival (EFS) and OS were 36% (95% confidence interval (CI); 29-43%) and 45% (95 CI; 38-51%), respectively. Relapse of primary disease was the cause of death in 81% of the population. EFS, OS, relapse and transplant-related mortality showed no significant differences when broken down by disease status at transplant, time from diagnosis to transplant, year of transplant or conditioning regimen. Our data suggest that HDT followed by autologous HCT for relapsed WT is well tolerated and outcomes are similar to those reported in the literature. As attempts to conduct a randomized trial comparing maintenance chemotherapy with consolidation versus HDT followed by stem cell transplant have failed, one should balance the potential benefits with the yet unknown long-term risks. As disease recurrence continues to be the most common cause of death, future research should focus on the development of consolidation therapies for those patients achieving complete response to therapy.

Nasal Nitric Oxide Measurement and a Modified PICADAR Score for the Screening of Primary Ciliary Dyskinesia in Adults with Bronchiectasis.

Background Determining the underlying diagnosis is essential for the targeted and specific treatment of bronchiectasis. Primary ciliary dyskinesia (PCD) is a rare genetic disease, which is characterized by abnormalities in ciliary structure and/or function and which may result in bronchiectasis. The disease is probably underestimated among adults with bronchiectasis due to the fact that extensive diagnostic testing is required and that the recognition of PCD is low. Objective To evaluate a feasible screening algorithm for PCD among adults with bronchiectasis. Methods Data from all patients who presented to our bronchiectasis outpatient clinic from June 2010 until July 2016 were retrospectively analysed from our database. Nasal NO (nNO) and a modified PICADAR score (PrImary CiliAry DyskinesiA Rule) were measured and compared in the two groups of PCD-bronchiectasis and non-PCD-bronchiectasis. Results 185 of 365 patients (75 males, 110 females) had a sufficient measurement of nNO concentration and complete clinical data and were eligible for analysis. The mean (SD) nNO concentration in nL/ml was significant lower in the PCD group compared to the non-PCD group (25 [31] and 227 [112] nL/min, respectively; p < 0.001). A nNO level of 77 nL/min had the best discriminative value to differentiate between the two groups. Patients with PCD had a significant higher modified PIDACAR score than patients without PCD (5 2 and 1 1, respectively [p < 0.001]). Using ROC curve analysis, the modified PICADAR score of 2 had the best discriminative value with a sensitivity of 1.00 and a specificity of 0.89. Conclusions Low nNO concentration and the modified PICADAR score are suitable and cheap screening tests for PCD in adults with bronchiectasis.

[New antibiotics - standstill or progress]. / Neue Antibiotika ­ Stillstand oder Fortschritt.

The development of resistance to antibiotics has been ignored for a long time. But nowadays, increasing resistance is an important topic. For a decade no new antibiotics had been developed and it is not possible to quickly close this gap of new resistance and no new drugs. This work presents six new antibiotics (ceftaroline, ceftobiprole, solithromycin, tedizolid, ceftolozane/tazobactam, ceftazidime/avibactam). In part, only expert opinions are given due to lack of study results.The two 5th generation cephalosporins ceftaroline and ceftobiprole have beside their equivalent efficacy to ceftriaxone (ceftaroline) and cefipim (ceftobiprole) high activity against MRSA. The fluoroketolide solithromycin should help against macrolide-resistant pathogens and has been shown to be noninferior to the fluorochinolones. The oxazolidinone tedizolid is effective against linezolid-resistant MRSA. The two cephalosporins ceftolozane/tazobactam and ceftazidime/avibactam are not only effective against gram-negative pathogens, but they have a very broad spectrum. Due to the efficacy against extended-spectrum ß­lactamases, they can relieve the selection pressure of the carbapenems. We benefit from all new antibiotics which can take the selection pressure from other often used antibiotics. The increasing number of resistant gram-negative pathogens worldwide is alarming. Thus, focusing on the development of new drugs is extremely important.

Statistical controversies in clinical research: Value of adverse events relatedness to study treatment: analyses of data from randomized double-blind placebo-controlled clinical trials.

BACKGROUND: Collection and reporting of adverse events (AEs) and their relatedness to study treatment, known commonly as attribution, in clinical trials is mandated by regulatory agencies (the National Cancer Institute and the Food and Drug Administration). Attribution is assigned by the treating physician using judgment based on various factors including patient's baseline status, disease history, and comorbidity as well as knowledge about the safety profile of the study treatments. We evaluate the patterns of AE attribution (unrelated, unlikely, possibly, probably, and definitely related to the treatment) in treatment, symptom intervention (cancer patients) and cancer prevention (participants at high risk for cancer) setting. MATERIALS AND METHODS: Nine multicenter placebo-controlled trials (two treatment, two symptom intervention, and five cancer prevention) were analysed separately (2155 patients). Frequency and severity of AEs were summarized by arm. Attribution and percentage of repeated AEs whose attribution changed overtime were summarized for the placebo arms. Percentage of physician over- or under-reporting of AE relatedness was calculated for the treatment arms using the placebo arm as the reference. RESULTS: Across all trials and settings, a very high proportion of AEs reported as related to treatment were classified as possibly related, a significant proportion of AEs in the placebo arm were incorrectly reported as related to treatment, and clinician-reported attribution over-estimated the rate of AEs related to treatment. Fatigue, nausea, vomiting, diarrhea, constipation, and neurosensory were the common AEs that were over reported by clinician as related to treatment. CONCLUSIONS: These analyses demonstrate that assigning causality to AE is a complex and difficult process that produces unreliable and subjective data. In randomized double-blind placebo-controlled trials where data are available to objectively assess relatedness of AE to treatment, attribution assignment should be eliminated.

[Nontuberculous mycobacterial pulmonary disease]. / Lungenerkrankung durch nichttuberkulöse Mykobakterien.

Nontuberculous mycobacteria (NTM) are a group of biologically diverse, ubiquitous and naturally multi-drug resistant bacteria with facultative pathogenicity. Recent data suggest that their clinical significance is increasing worldwide and that susceptible individuals may be at risk for infection via contaminated surfaces and aerosols. These individuals often have a predisposition for chronic respiratory diseases, e. g. bronchiectasis, chronic obstructive pulmonary disease (COPD) and cystic fibrosis and these conditions frequently share the same unspecific signs and symptoms with NTM pulmonary disease (NTM-PD). As a consequence, the diagnosis of NTM-PD, which is established based on clinical, radiological and microbiological criteria, is often delayed. Treating NTM-PD is more demanding than treating pulmonary tuberculosis as therapy is generally more tedious, toxic and expensive as well as being prone to failure. Patient and pathogen-specific factors guide the choice of an appropriate antimicrobial combination regimen, which should comply with national and international recommendations. Adverse events are common, should be anticipated and closely monitored. If infections with infrequently encountered mycobacterial species and severe or refractory disease occur, an interdisciplinary approach should be used, involving infectious disease specialists, experienced thoracic surgeons and referral to an NTM specialist center.

[Specific infections in organ transplantation]. / Spezifische Infektionen bei Organtransplantationen.

This article is concerned with the important topic of infections associated with organ transplantation and includes a discussion on four subtopics. The first section describes the current options in the prevention and therapy of viral hepatitis in association with liver transplantation. Infections with hepatitis B, C, D (delta) and E are discussed with special emphasis on the interferon-free treatment of hepatitis C with the new antiviral drugs.The second section deals with Pseudomonas aeruginosa (PA) infections following lung transplantation (LuTx), which is one of the most frequently detected pathogens in the airway after LuTx. Patients with cystic fibrosis are particularly affected. This is important because studies have shown a clear correlation between chronic PA infections after LuTx and development of chronic transplant failure. Even if the data are still sparse, recommendations on prevention and therapeutic strategies are given. The theme of the third section is the high importance of viral infections after kidney transplantation. In addition to acquired infections, the transplanted organ as well as the recipient can be the source of the infection. The better the transplanted organ is tolerated under moderate immunosuppression, the less common and severe virus infections are. The focus of this section is on three common pathogens: cytomegalovirus, polyomavirus BK and hepatitis viruses.The final section deals with Aspergillus infections following transplantation of various organs. In this context Aspergillus spp. are one of the most commonly occurring fungal diseases. The epidemiology, risk factors, diagnostics, prophylaxis and therapy of invasive aspergillosis are presented.

[PROGNOSIS - The PROspective German NOn-CF BronchiectaSIS Patient Registry]. / PROGNOSIS - das deutsche Bronchiektasen-Register.

Bronchiectasis not due to cystic fibrosis (Non-CF bronchiectasis) represents a heterogeneous disorder with many different underlying diseases. Reliable and mature data referring to prevalence and incidence of Non-CF bronchiectasis in Germany are lacking. Bronchiectasis is often mentioned as rare or orphan disease, although it might be more often than supposed to be. Up to now (May 2015) there is no approved therapy for this disease in Germany. After some preliminary work the German bronchiectasis registry PROGNOSIS (The PROspective German NOn-CF bronchiectaSIS patient registry) will start recruiting patients by the beginning of July. The goals of PROGNOSIS are to build up a national, representative, prospective, observing (non-interventional) and longitudinal patient registry with at least 750 patients within three years in 25-35 centers, to evaluate important epidemiological questions. In addition a German-language guideline for diagnostic and management of Non-CF bronchiectasis will be developed in cooperation with the German respiratory society (DGP).

Striped pattern selection by advective reaction-diffusion systems: resilience of banded vegetation on slopes.

For water-limited arid ecosystems, where water distribution and infiltration play a vital role, various models have been set up to explain vegetation patterning. On sloped terrains, vegetation aligned in bands has been observed ubiquitously. In this paper, we consider the appearance, stability, and bifurcations of 2D striped or banded patterns in an arid ecosystem model. We numerically show that the resilience of the vegetation bands is larger on steeper slopes by computing the stability regions (Busse balloons) of striped patterns with respect to 1D and transverse 2D perturbations. This is corroborated by numerical simulations with a slowly decreasing water input parameter. Here, long wavelength striped patterns are unstable against transverse perturbations, which we also rigorously prove on flat ground through an Evans function approach. In addition, we prove a "Squire theorem" for a class of two-component reaction-advection-diffusion systems that includes our model, showing that the onset of pattern formation in 2D is due to 1D instabilities in the direction of advection, which naturally leads to striped patterns.

[Therapy of bronchiectasis]. / Therapie von Bronchiektasen.

The prevalence of bronchiectasis not due to cystic fibrosis (NCFB) increases with older age. Because of multifaceted etiology of bronchiectasis an extensive diagnostic approach is essential. This includes in-depth anamnesis and a high resolution CT scan of the chest (HRCT). The pathophysiological mechanism with infection, inflammation, secretion retention and destruction determine the therapeutic options. In patients with high rates of exacerbations and severe diseases physicians should think of inhaled antibiotics and macrolids. In case of localized bronchiectasis and failure of conventional therapy surgery of bronchiectasis is an effective treatment option. In some cases surgery is necessary due to haemoptysis, aspergilloma, lung abscess and pleuraempyema. To improve the treatment options of bronchiectasis results of epidemiological, basically and clinical research trials are expected and needed.

Comparison of non-myeloablative conditioning regimens for lymphoproliferative disorders.

Hematopoietic cell transplantation (HCT) with non-myeloablative (NMA) conditioning for lymphoproliferative diseases (LD) includes fludarabine with and without low-dose TBI. Transplant outcomes were compared among patients aged ⩾40 years with LD who received a HCT with TBI (N=382) or no-TBI (N=515) NMA from 2001 to 2011. The groups were comparable except for donor, graft, prophylaxis for GVHD, disease status and year of HCT. Cumulative incidences of grades II-IV GVHD at 100 days were 29% and 20% (P=0.001) and of chronic GVHD at 1 year were 54% and 44% (P=0.004) for TBI and no-TBI, respectively. Multivariate analysis of progression/relapse, treatment failure and mortality showed no outcome differences by conditioning. Full donor chimerism at day 100 was observed in 82% vs 64% in the TBI and no-TBI groups, respectively (P=0.006). Subsets of the four most common conditioning/GVHD prophylaxis combinations demonstrated higher rates of grades II-IV acute (P<0.001) and chronic GVHD (P<0.001) among recipients of TBI-mycophenolate mofetil (MMF) compared with other combinations. TBI-based NMA conditioning induces faster full donor chimerism, but overall survival outcomes are comparable to no-TBI regimens. Combinations of TBI and MMF are associated with higher rates of GVHD without impact on survival outcomes in patients with LD.

Autologous CD133+ cells augment the effect of portal embolization.

AIM: The standard to treat liver tumors is a resection. When the future liver remnant (FLRV) is below 30% (healthy livers) or 40% (cirrhotic livers or previous chemotherapy), surgery carries the risk of severe complications. Portal vein embolization (PVE) gained a worldwide diffusion as a tool to augment the FLRV. Cell therapies are recent players at the frontiers of medicine. This study presents a clinical experience to evaluate the synergistic effect of combined PVE and autologous CD133+ cells coadministration. METHODS: Sixteen patients have been enrolled in the study up today. Inclusion criteria were: primary or metastatic liver malignancy with a FLRV<30% or 40%. A baseline volumetric CT-scan was obtained. CD34+ were mobilized to the blood stream by G-CSF administration and collected by immunomagnetic separation. Simultaneously with PVE, cells were administered to the non occluded liver segments. Follow-up CT scans were taken at 30th post treatment day. RESULTS: The patients (N.=6) showed an increased volume gain (Mann-Whitney test P<0.001, two sided) compared to a set of cases whose treatment was PVE only (N.=10). DISCUSSION: The use of autologous stem cells as an augmenter of liver regeneration has a clinical potential to improve the resectability of liver tumors.

Phenotyping established chronic lung allograft dysfunction predicts extracorporeal photopheresis response in lung transplant patients.

Chronic lung allograft dysfunction (CLAD) remains the leading cause of mortality in lung transplant recipients after the first year. Treatment remains limited and unpredictable. Existing data suggests extracorporeal photopheresis (ECP) may be beneficial. This study aimed to identify factors predicting treatment response and the prognostic implications. A single center retrospective analysis of all patients commencing ECP for CLAD between November 1, 2007 and September 1, 2011 was performed. In total 65 patients were included, 64 of whom had deteriorated under azithromycin. Median follow-up after commencing ECP was 503 days. Upon commencing ECP, all patients were classified using proposed criteria for emerging clinical phenotypes, including "restrictive allograft syndrome (RAS)", "neutrophilic CLAD (nCLAD)" and "rapid decliners". At follow-up, 8 patients demonstrated ≥10% improvement in FEV1 , 27 patients had stabilized and 30 patients exhibited ≥10% decline in FEV1 . Patients fulfilling criteria for "rapid decliners" (n=21, p=0.005), RAS (n=22, p=0.002) and those not exhibiting neutrophilia in bronchoalveolar lavage (n=44, p=0.01) exhibited poorer outcomes. ECP appears an effective second line treatment in CLAD patients progressing under azithromycin. ECP responders demonstrated improved progression-free survival (median 401 vs. 133 days). Proposed CLAD phenotypes require refinement, but appear to predict the likelihood of ECP response.

[Treatment of not-with cystic fibrosis associated forms bronchiectasis (non-CF bronchiectasis)]. / Behandlung nicht mit zystischer Fibrose assoziierter Bronchiektasen (Non-CF-Bronchiektasen).

Bronchiectasis has become more rarely because of the development of antibiotic therapy and vaccination. At present the great majority of bronchiectasis is more likely caused by congenital disorders than by infective reasons. Therapeutic strategies based on the experiences from cystic fibrosis and chronic obstructive pulmonary disease are not always conferrable to patients suffering from bronchiectasis. There are not enough controlled studies to give evidence-based recommendations in the treatment of bronchiectasis, which are not associated with cystic fibrosis. Goals in the treatment are improvement of the mucociliar clearance, the therapy of infections and treatment of inflammation. Currently several agents are under examination. To improve the prognosis and therapy options it would be reasonable to build up a national register for patients with bronchiectasis.