A compact setup for behavioral studies measuring limb acceleration.

Behavioral studies contribute largely to a broader understanding of human brain mechanisms and the process of learning and memory. An established method to quantify motor learning is the analysis of thumb activity. In combination with brain stimulation, the effect of various treatments on neural plasticity and motor learning can be assessed. So far, the setups for thumb abduction measurements employed consist of bulky amplifiers and digital-to-analog devices to record the data. We developed a compact hardware setup to measure acceleration data which can be integrated into a wearable, including a sensor board and a microcontroller board which can be connected to a PC via USB. Additionally, we provide two software packages including graphical user interfaces, one to communicate with the hardware and one to evaluate and process the data. This work demonstrates the construction and application of our setup at the example of thumb acceleration measurement with a custom made glove and its use for research. Using integrated circuits, the size of the measurement devices is reduced to this wearable. It is simple to construct and can be operated easily by non-technical staff.

Complexity of patients with or without infectious disease consultation in tertiary-care hospitals in Germany.

PURPOSE: Patients seen by infectious disease (ID) specialists are more complex compared to patients treated by other subspecialities according to Tonelli et al. (2018). However, larger studies on the complexity of patients related to the involvement of ID consultation services are missing. METHODS: Data of patients being treated in 2015 and 2019 in four different German university hospitals was retrospectively collected. Data were collected from the hospitals' software system and included whether the patients received an ID consultation as well as patient clinical complexity level (PCCL), case mix index (CMI) and length of stay (LOS) as a measurement for the patients' complexity. Furthermore, a comparison of patients with distinct infectious diseases treated with or without an ID consultation was initiated. RESULTS: In total, 215.915 patients were included in the study, 3% (n = 6311) of those were seen by an ID consultant. Patients receiving ID consultations had a significantly (p < 0.05) higher PCCL (median 4 vs. 0), CMI (median 3,8 vs. 1,1) and deviation of the expected mean LOS (median 7 days vs. 0 days) than patients in the control group. No differences among hospitals or between years were observed. Comparing patients with distinct infectious diseases treated with or without an ID consultation, the differences were confirmed throughout the groups. CONCLUSION: Patients receiving ID consultations are highly complex, frequently need further treatment after discharge and have a high economic impact. Thus, ID specialists should be clinically trained in a broad spectrum of diseases and treating these complex patients should be sufficiently remunerated.

[Precision medicine in infectious diseases]. / Präzisionsmedizin in der Infektiologie.

Infectious medicine faces a variety of challenges, such as the increase in antibiotic resistance and the emergence and spread of infectious diseases fueled by climate change and globalization. Precision medicine can provide solutions to many of these challenges. Since an untargeted request for diagnostic tests can lead to test results without clinical relevance, which can increase the use of non-indicated antibiotics, the principle aimed at is: targeted diagnostics (the right test) and consideration of patient characteristics (the right person) to optimize management (the right action). At the same time, one must always decide whether empirical therapy must be immediately initiated, even if the results of the initiated diagnostics are not yet available. In addition, many new diagnostics as well as therapies have recently been developed for the rapid detection and more specific treatment of bacterial infections. Molecular genetic methods, which offer more rapid results than classical bacterial cultures, are gaining ground as new diagnostics. New therapeutics such as bacteriophages, antibodies or antibacterial peptides allow increasingly precise treatment of certain bacterial infections. Precision medicine will also play an increasingly important role in infectious medicine in the future.

Can we predict favourable quality of life after surgically treated vertebral osteomyelitis? Analysis of a prospective study.

PURPOSE: Vertebral osteomyelitis (VO) is a severe clinical entity associated with significant morbidity and mortality. Several studies have showed that successful treatment of VO patients leads to significantly improved quality of life (QoL). Nevertheless, QoL levels of these patients remained below those of the general population. There are rarely studies focusing on predicting factors for favourable QoL after surgically treated VO. The aim of this study was to identify factors influencing positively the QoL of patients undergoing surgery for VO. METHODS: We conducted a prospective monocentric study including surgically treated VO patients from 2008 to 2016. Data were collected before (T0) and 1 year (T1) after surgery. Primary outcome was favourable QoL defined as back pain with disability restricting normal life activity with a cutoff value ≥ 12 on Oswestry Disability Index (ODI). ETHICS: Ethical approval was given by the Faculty of Medicine at the University of Cologne (09-182). RESULTS: A total of 119 patients surviving 1 year after surgically treated VO were analysed. Favourable QoL was achieved in 35/119 patients. On multivariate analysis, younger age (hazard ratio = HR: 0.95; 95% CI 0.91-0.99; p = 0.022), lower albumin (HR: 0.9; 0.83-0.98; p = 0.019) an ASA score ≤ 2 (HR:4.24; 95%CI 1.42-12.68; p = 0.010), and a lower preoperative leg pain on the VAS (HR: 0.86; 95% CI 0.76-0.97; p = 0.018) were identified as independent risk factors for favourable QoL. Interestingly, the absence of neurological deficits was not predictive for a favourable outcome by means of QoL. CONCLUSION: One-third of surgically treated VO patients (29%) in our cohort achieved favourable QoL by means of ODI. Our findings can facilitate an estimation of the prognosis when informing the patient before surgery, and underscore that spine disability questionnaires, such as ODI, measuring QoL, are mandatory to evaluate comprehensively the outcome of this entity.

National strategy for palliative care of severely ill and dying people and their relatives in pandemics (PallPan) in Germany - study protocol of a mixed-methods project.

BACKGROUND: In the SARS-CoV-2 pandemic, general and specialist Palliative Care (PC) plays an essential role in health care, contributing to symptom control, psycho-social support, and providing support in complex decision making. Numbers of COVID-19 related deaths have recently increased demanding more palliative care input. Also, the pandemic impacts on palliative care for non-COVID-19 patients. Strategies on the care for seriously ill and dying people in pandemic times are lacking. Therefore, the program 'Palliative care in Pandemics' (PallPan) aims to develop and consent a national pandemic plan for the care of seriously ill and dying adults and their informal carers in pandemics including (a) guidance for generalist and specialist palliative care of patients with and without SARS-CoV-2 infections on the micro, meso and macro level, (b) collection and development of information material for an online platform, and (c) identification of variables and research questions on palliative care in pandemics for the national pandemic cohort network (NAPKON). METHODS: Mixed-methods project including ten work packages conducting (online) surveys and qualitative interviews to explore and describe i) experiences and burden of patients (with/without SARS-CoV-2 infection) and their relatives, ii) experiences, challenges and potential solutions of health care professionals, stakeholders and decision makers during the SARS-CoV-2 pandemic. The work package results inform the development of a consensus-based guidance. In addition, best practice examples and relevant literature will be collected and variables for data collection identified. DISCUSSION: For a future "pandemic preparedness" national and international recommendations and concepts for the care of severely ill and dying people are necessary considering both generalist and specialist palliative care in the home care and inpatient setting.

Outbreak of Pseudomonas aeruginosa infections after CT-guided spinal injections.

BACKGROUND: Meningitis and spinal infections with Gram-negative bacteria after local injections for treatment of chronic back pain are rare. This study investigated an outbreak of Pseudomonas aeruginosa infections following computed tomography (CT)-guided spinal injections (SI). METHODS: A case was defined as a spinal infection or meningitis with P. aeruginosa after SI between 10th January and 1st March 2019 in the same outpatient clinic. Patients without microbiological evidence of P. aeruginosa but with a favourable response to antimicrobial therapy active against P. aeruginosa were defined as probable cases. FINDINGS: Twenty-eight of 297 patients receiving CT-guided SI during the study period developed meningitis or spinal infections. Medical records were available for 19 patients. In 15 patients, there was microbiological evidence of P. aeruginosa, and four patients were defined as probable cases. Two of 19 patients developed meningitis, while the remaining 17 patients developed spinal infections. The median time from SI to hospital admission was 8 days (interquartile range 2-23 days). Patients mainly presented with back pain (N=18; 95%), and rarely developed fever (N=3; 16%). Most patients required surgery (N=16; 84%). Seven patients (37%) relapsed and one patient died. Although the source of infection was not identified microbiologically, documented failures in asepsis when performing SI probably contributed to these infections. CONCLUSIONS: SI is generally considered safe, but non-adherence to asepsis can lead to deleterious effects. Spinal infections caused by P. aeruginosa are difficult to treat and have a high relapse 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.

Predictors of serofast state after treatment for early syphilis in HIV-infected patients.

OBJECTIVES: Non-treponemal serological tests are used to monitor treatment response during syphilis infection. Syphilis- and HIV-coinfected patients may experience incomplete resolution in non-treponemal titres, which is referred to as the serofast state. The goal of this study was to evaluate risk factors for serofast state in HIV-infected patients. METHODS: From November 2015 to June 2018, 1530 HIV-positive patients were tested for syphilis using a Treponema pallidum particle agglutination (TPPA) assay. Among TPPA-positive patients, medical records were reviewed for early syphilis infection. Serofast state was defined as a less than four-fold decrease in non-treponemal antibody titres during a 6-month follow-up period in the absence of symptoms of syphilis. Baseline characteristics were tested as predictive factors of serological response. RESULTS: In all, 515 patients (33.7%) tested positive in TPPA assays, and in 163 patients at least one previous syphilis infection was documented. A total of 61 out of 163 patients (37.4%) were in a serofast state. A history of previous syphilis infection (61 vs. 43%; P = 0.04) was more common in serofast patients than in patients with serological cure after 6 months. Non-treponemal titres ≥ 1:32 before therapy (47 vs. 25%; P = 0.005) and adjunctive corticosteroids to prevent the Jarisch-Herxheimer reaction (35% vs 15%; P = 0.006) were associated with serological cure after 6 months, but corticosteroid therapy had no influence at 12 months. The intensity of syphilis treatment did not affect serological cure. CONCLUSION: Corticosteroids for prevention of the Jarisch-Herxheimer reaction were associated with earlier serological cure. Although serological response is the accredited surrogate method to monitor syphilis treatment, the biological significance of the serofast state remains unclear.

A simple and efficient method of generating HCMV pp65-specific T cells using overlapping peptides.

The methods for expansion of human cytomegalovirus (HCMV)-specific T lymphocytes are limited due to the complex culture process, long culture duration, and human leukocyte antigen (HLA) restriction. Here, we report that in vitro stimulation with pp65 kDa phosphoprotein (pp65)-derived overlapping synthetic peptides rapidly generates large numbers of HCMV-specific cytotoxic T lymphocytes from peripheral blood mononuclear cells (PBMCs) regardless of HLA type. Treatment of PBMCs from healthy volunteers expressing HLA-A*02:01 or HLA-A*24:02 with 138 pp65 overlapping peptides (OLP) resulted in an expansion of HCMV pp65 NLVPMVATV (NLV) pentamer-specific CD8+ T lymphocytes that expressed interferon (IFN)-γ, but the pp65 NLV peptide did not generate HCMV-specific CD8+ T lymphocytes in PBMCs obtained from an HLA-A*24:02 donor due to HLA restriction. The OLP-induced T lymphocytes specific for HCMV derived from PBMCs of HLA-A*02:01- and HLA-A*24:02-expressing donors showed effective cytolytic responses against target cells loaded with OLP or the NLV epitope, but pp65 NLV peptide-induced T lymphocytes did not. Phenotypic analyses demonstrated that OLP increased the frequency of CD3+ CD8+ cells, but not CD3+ CD4+, CD14+, or CD56+ cells, in donor PBMCs. Thus, this study provides evidence that in vitro stimulation with OLP efficiently generates sufficient numbers of HCMV pp65-specific cytotoxic T lymphocytes for adoptive cell therapy. Keywords: human cytomegalovirus; cytotoxic T lymphocyte; overlapping peptides; pp65; cytotoxicity.

[Various scenarios for billing and remuneration of preoperative management of iron deficiency anemia in the German healthcare system]. / Verschiedene Szenarien zu Abrechnung und Kostenerstattung eines präoperativen Managements der Eisenmangelanämie im deutschen Gesundheitssystem.

More than 30% of all patients undergoing surgery suffer from preoperative anemia. Iron deficiency anemia is the most common type of anemia. The diagnostics and treatment of iron deficiency anemia can be carried out before patients undergo surgery as an alternative to blood transfusion and is an interdisciplinary task. This article gives an overview of various billing modalities and payment arrangements for management of preoperative anemia in the German healthcare system.

Current clinical use of intravenous fosfomycin in ICU patients in two European countries.

PURPOSE: In Europe, intravenous fosfomycin (IV) is used particularly in difficult-to-treat or complex infections, caused by both Gram-positive and Gram-negative pathogens including multidrug-resistant strains. Here, we investigated the efficacy and safety of intravenous fosfomycin under real-life conditions. METHODS: Prospective, multi-center, and non-interventional study in patients with bacterial infections from 20 intensive care units (ICU) in Germany and Austria (NCT01173575). RESULTS: Overall, 209 patients were included (77 females, 132 males, mean age: 59 ± 16 years), 194 of which were treated in intensive care (APACHE II score at the beginning of fosfomycin therapy: 23 ± 8). Main indications (± bacteremia or sepsis) were infections of the CNS (21.5%), community- (CAP) and hospital-acquired pneumonia (HAP)/ventilator-associated pneumonia (VAP, 15.3%), bone and joint infections (BJI, 11%), abdominal infections (11%), and bacteremia (10.5%). Most frequently identified pathogens were S. aureus (22.3%), S. epidermidis (14.2%), Enterococcus spp. (10.8%), E. coli (12.3%) and Klebsiella spp. (7.7%). At least one multidrug-resistant (MDR) pathogen was isolated from 51 patients (24.4%). Fosfomycin was administered with an average daily dose of 13.7 ± 3.5 g over 12.4 ± 8.6 days, almost exclusively (99%) in combination with other antibiotics. The overall clinical success was favorable in 81.3% (148/182) of cases, and in 84.8% (39/46) of patients with ≥ 1 MDR pathogen. Noteworthy, 16.3% (34/209) of patients developed at least one, in the majority of cases non-serious, adverse drug reaction during fosfomycin therapy. CONCLUSION: Our data suggest that IV fosfomycin is an effective and safe combination partner for the treatment of a broad spectrum of severe bacterial infections in critically ill patients.

Regulation of neutrophil pro-inflammatory functions sheds new light on the pathogenesis of rheumatoid arthritis.

For more than two centuries now, rheumatoid arthritis (RA) is under investigation intending to discover successful treatment. Despite decades of scientific advances, RA is still representing a challenge for contemporary medicine. Current drug therapies allow to improve significantly the quality of life of RA patients; however, they are still insufficient to reverse tissue injury and are often generating side-effects. The difficulty arises from the considerable fluctuation of the clinical course of RA among patients, making the predictive prognosis difficult. More and more studies underline the profound influence of the neutrophil multifaceted functions in the pathogenesis of RA. This renewed interest in the complexity of neutrophil functions in RA offers new exciting opportunities for valuable therapeutic targets as well as for safe and well-tolerated RA treatments. In this review, we aim to update the recent findings on the multiple facets of neutrophils in RA, in particular their impact in promoting the RA-based inflammation through the release of the cytokine-like S100A8/A9 protein complex, as well as the importance of NETosis in the disease progression and development. Furthermore, we delve into the complex question of neutrophil heterogeneity and plasticity and discuss the emerging role of miRNAs and epigenetic markers influencing the inflammatory response of neutrophils in RA and how they could constitute the starting point for novel attractive targets in RA therapy.

Essentials in Candida bloodstream infection.

AIMS: Due to the increase of severely immunocompromised patients, of invasive procedures including central intravascular catheters, and of the use of broad-spectrum antibiotics, the incidence of Candida bloodstream infections has risen intensely in the last decades. Candida bloodstream infection is a serious disease with high mortality. Optimized diagnostic and therapeutic management can improve outcome. Thus, the aim of our mini-review is to highlight important and often missed opportunities in the management of Candida bloodstream infection. METHODS: We searched the published literature and describe the essentials in the management of Candida bloodstream infection. RESULTS: Four essentials were identified: (1) isolation of Candida spp. from a blood culture should always be considered relevant and requires treatment. Daily blood cultures should be drawn to determine cessation of candidemia. (2) Central venous catheter (CVC) and/or other indwelling devices should be removed. (3) Echinocandins are the first choice. Antifungal treatment should be continued for at least 14 days after cessation of fungemia. Susceptibility testing should be performed to identify resistance and to facilitate transition to oral treatment. (4) In persistent candidemia, echocardiography is an important investigation; ophthalmoscopy should be considered. CONCLUSION: Further efforts should be undertaken to increase the adherence to the essentials in the management of Candia bloodstream infection.

[Neuronal plasticity and neuromodulation in pediatric neurology]. / Neuronale Plastizität und Neuromodulation in der Kinderneurologie.

BACKGROUND: Neuronal plasticity is a core mechanism for learning and memory. Abnormal neuronal plasticity has emerged as a key mechanism in many neurological and neuropediatric diseases. OBJECTIVE: Chances and perspectives of neuromodulation techniques in neurological and neuropediatric diseases with altered neuronal plasticity. MATERIAL AND METHODS: Presentation and discussion of own results of neuronal plasticity investigations in patients with neurodevelopmental disorders including RASopathies, autism spectrum disorders (ASD) and Gilles de la Tourette syndrome (GTS). RESULTS: The results of neuronal plasticity studies in patients with RASopathies, ASD and GTS underline the pathophysiological relevance of abnormal neuronal plasticity in these diseases. Transcranial magnetic stimulation (TMS) is a useful tool to examine and also induce neuronal plasticity in these patients. CONCLUSION: Neuronal plasticity appears to be an important pathophysiological factor in neuronal developmental disorders and can be investigated using TMS. New and innovative techniques may offer novel approaches for individualized TMS applications, particularly in children with neuropediatric conditions.

To prescribe, or not to prescribe: decision making in HIV-1 post-exposure prophylaxis.

OBJECTIVES: We investigated the trend in usage of post-exposure prophylaxis (PEP) after HIV-1 risk exposure and evaluated PEP prescription decision making of physicians according to guidelines. METHODS: All PEP consultations from January 2014 to December 2016 in patients presenting at the University Hospital of Cologne (Germany) were retrospectively analysed. HIV risk contacts included sexual and occupational exposure. The European AIDS Clinical Society (EACS) Guidelines for HIV PEP (version 9.0, 2017) were used for assessment. RESULTS: A total of 649 patients presented at the emergency department (ED) or the clinic for infectious diseases (IDC) for PEP consultations. A continuous increase in the number of PEP requests was recorded: 189 in 2014, 208 in 2015 and 252 in 2016. PEP consultations in men who have sex with men (MSM) showed a remarkable increase in 2016 (2014, n = 96; 2015, n = 101; 2016, n = 152). Decisions taken by physicians with a specialization in infectious diseases (n = 547) included 61 (11%) guideline-discordant prescriptions [2014: 14% (n = 22); 2015: 9% (n = 16); 2016: 11% (n = 23)]. Among these, sexual exposure accounted for 45 (74%) cases, including 15 cases of nonconsensual sex, while occupational exposure accounted for 14 (23%) cases and other exposure two cases (3%). The main reason for guideline-discordant PEP prescriptions was emotional stress of the patient (n = 37/61). CONCLUSIONS: PEP prescriptions are increasing and decision making is influenced by patients' emotional stress, but PEP prescriptions should be strictly administered according to risk assessment.

Essentials in the management of S. aureus bloodstream infection.

AIMS: Staphylococcus aureus bloodstream infection is one of the most common serious bacterial infections worldwide. It represents a heterogenous clinical entity with a high risk of metastatic complications and a high in-hospital mortality ranging between 20 and 30%. The outcome can be improved by optimised diagnostic and therapeutic management. Thus, our minireview should provide important and often missed pieces of information in the management of S. aureus bloodstream infection. METHODS: We describe the essentials in the management of S. aureus bloodstream infection. RESULTS: Five essentials were identified: 1) S. aureus bacteremia should always be considered clinically significant. 2) Length of bacteremia and fever is relevant for diagnostic workup, duration of therapy and prognosis. 3) Prompt identification and eradication of portal of entry and infective/metastatic foci are essential. 4) Infective endocarditis should be excluded. 5) Intravenous treatment for at least two weeks up to 4-6 weeks with antistaphylococcal penicillins for MSSA and vancomycin or daptomycin for MRSA bloodstream infection is indicated. CONCLUSION: Further efforts should be undertaken to increase the adherence to the essentials in the management of S. aureus bloodstream infection.

[Infectious diseases - a specialty of internal medicine]. / Infektiologie ­ ein Schwerpunkt der Inneren Medizin.

Infectious diseases have recently gained wide public interest. Emerging infections and rising rates of antibiotic resistance are determining this trend. Both challenges will need to be addressed in international and local collaborations between different specialties in medicine and basic science. Infectious diseases as a clinical specialty in this scenario is directly responsible for the care of patients with infectious diseases. Its involvement in the care of patients with complicated infections has proved to be highly effective. Antibiotic stewardship programmes are effective measures in slowing the development of antibiotic resistance and have been widely implemented. But antibiotic stewardship specialists should not be confused with or taken as an alternative to infectious disease experts. Infectious diseases requires appropriate and specific training. It mainly uses the instrumentarium of internal medicine. With the current challenges in modern medicine, infectious diseases in Germany should thus be upgraded from a subspecialty to a clinical specialty, ideally within Internal Medicine.