Human cytomegalovirus seropositivity is associated with reduced patient survival during sepsis.

BACKGROUND: Sepsis is one of the leading causes of death. Treatment attempts targeting the immune response regularly fail in clinical trials. As HCMV latency can modulate the immune response and changes the immune cell composition, we hypothesized that HCMV serostatus affects mortality in sepsis patients. METHODS: We determined the HCMV serostatus (i.e., latency) of 410 prospectively enrolled patients of the multicenter SepsisDataNet.NRW study. Patients were recruited according to the SEPSIS-3 criteria and clinical data were recorded in an observational approach. We quantified 13 cytokines at Days 1, 4, and 8 after enrollment. Proteomics data were analyzed from the plasma samples of 171 patients. RESULTS: The 30-day mortality was higher in HCMV-seropositive patients than in seronegative sepsis patients (38% vs. 25%, respectively; p = 0.008; HR, 1.656; 95% CI 1.135-2.417). This effect was observed independent of age (p = 0.010; HR, 1.673; 95% CI 1.131-2.477). The predictive value on the outcome of the increased concentrations of IL-6 was present only in the seropositive cohort (30-day mortality, 63% vs. 24%; HR 3.250; 95% CI 2.075-5.090; p < 0.001) with no significant differences in serum concentrations of IL-6 between the two groups. Procalcitonin and IL-10 exhibited the same behavior and were predictive of the outcome only in HCMV-seropositive patients. CONCLUSION: We suggest that the predictive value of inflammation-associated biomarkers should be re-evaluated with regard to the HCMV serostatus. Targeting HCMV latency might open a new approach to selecting suitable patients for individualized treatment in sepsis.

Anatomic considerations of inflatable penile prosthetics: lessons gleaned from surgical body donor workshops.

Surgical implantation of an inflatable penile prosthesis (IPP) remains the gold-standard treatment for severe erectile dysfunction. The ideal surgical technique requires a thorough understanding of the relevant anatomy. This includes anatomic considerations related to, but not limited to, dissection and exposure of penoscrotal fasciae and tissues, corporal configuration, and abdominal structures. Insights obtained from pre-dissected anatomic specimens can obviate urethral injury, nerve damage, corporal perforation, inappropriate sizing, crossover, or implant malposition. We present penile implant-specific anatomic dissections and topographic landmarks identified over the last decade in the course of surgical training programs provided for IPP implantation.

Energy values of crude glycerin for broilers / [Valores energéticos da glicerina bruta para frango de corte]

The energetic values of crude glycerin (CG) were determined for broilers at different ages using the method proposed by Matterson and by polynomial regressions. Two trials were performed with broilers from 11 to 21 and from 31 to 41 days of age. The birds were distributed in a completely randomized experimental design with a reference ration (RR), without CG, and three ration tests with replacement of 5%, 10%, and 15% of RR by CG. The metabolizable energy values were calculated by the Matterson method, and the apparent metabolizable energy (AME) values were used in polynomial regression analysis. The mean values of AME, apparent corrected for nitrogen balance (AMEn), metabolizable coefficient of gross energy (CAMEB), and corrected for nitrogen balance (CAMEBn) of CG, for the phase from 11 to 21 days by the Matterson method were 10.08 MJ kg-1, 10.04 MJ kg-1, 67.06%, and 66.74%, respectively. The inclusion of CG presented an increasing linear effect for CAMEB and CAMEBn in this period. From 31 to 41 days, these values were 10.38 MJ kg-1, 10.27 MJ kg-1, 69.02%, and 62.24%, respectively. The predicted AMEn value through the polynomial regression equations was 10.49 MJ kg-1 and 10.18 MJ kg-1, respectively. According to the equations proposed by Matterson, the crude glycerin EMAn values for broilers from 11 to 21 and 31 to 41 days of age were 10.04 MJ kg-1 and 10.26 MJ kg-1, respectively. According to Adeola's method the AMEn values were 10.49 and 10.20 MJ kg-1 for each phase.(AU)

Os valores energéticos da glicerina bruta (GB) foram determinados para frangos de corte em diferentes idades, por meio da utilização do método proposto por Matterson e de regressões polinomiais. Foram realizados dois ensaios: de 11 a 21 dias e de 31 a 41 dias de idade das aves; em ambos, as aves foram distribuídas em um delineamento experimental inteiramente ao acaso, com uma ração referência (RR), sem GB, e três rações testes com substituição de 5%, 10% e 15% da RR por GB. Foram calculados os valores de energia metabolizável pelo método de Matterson, sendo os valores de energia metabolizável aparente (EMA) utilizados na análise de regressão polinomial. Os valores médios da EMA corrigida pelo balanço de nitrogênio (EMAn), o coeficiente de metabolizabilidade da EB (CMAEB) e o corrigido para o balanço de nitrogênio (CMAEBn) da GB, na matéria natural, para a fase de 11 a 21 dias, pelo método de Matterson, foram de 10,08 MJ kg-1, 10,04 MJ kg-1, 67,06% e 66,74%, respectivamente. A inclusão de GB apresentou um efeito linear crescente para os CMAEB e os CMAEBn. Na fase de 31 a 41 dias, foram de 10,38 MJ kg-1, 10,27 MJ kg-1, 69,02% e 62,24%, respectivamente. Por meio das equações de regressões polinomiais, o valor de EMAn estimada foi de 10,49 MJ kg-1 e 10,18 MJ kg-1, respectivamente. Os valores de EMAn da GB para as idades 11 a 21 e 31 a 41 dias foram de 10,04 MJ kg-1 e 10,26 MJ kg-1, respectivamente. De acordo com as equações propostas por Matterson e com o método de Adeola, os valores de EMAn foram 10,49 e 10,20 MJ kg-1 para cada fase.(AU)

Polycentric Exoprosthetic Knee Joints - Extent of Shortening During Swing Phase.

BACKGROUND: An often assumed advantage of polycentric knee joints compared to monocentric ones is the improved ground clearance during swing phase due to the geometric shortening of the lower leg segment (LLS). OBJECTIVE: To investigate whether polycentric knee joints considerably improve ground clearance and to evaluate the influence of prosthetic alignment on the extent of ground clearance. METHODOLOGY: 11 polycentric and 2 monocentric knee joints were attached to a rigid, stationary testing device. Shortening of the LLS and the resulting ground clearance during knee flexion were measured. Prosthetic components were mounted at the same height and the anterior-posterior position was in accordance with the manufacturer's alignment recommendations. FINDINGS: Shortening of up to 14.7 (SD=0.0) mm at the instance of minimal ground clearance during swing phase was measured. One knee joint elongated by 4.4 (SD=0.0) mm. Measurements of the ground clearance demonstrated differences up to 25.4 (SD=0.0) mm. One monocentric knee joint provided more ground clearance when compared to 8 of the polycentric knee joints investigated. CONCLUSION: Only some polycentric knee joints shorten appreciably during swing phase. With an optimized prosthetic alignment and a well-designed swing phase control, a monocentric knee joint may generate greater ground clearance compared to a polycentric knee joint.

The value of bronchoalveolar lavage for discrimination between healthy and diseased individuals.

BACKGROUND: Bronchoalveolar lavage (BAL) is standard diagnostic procedure. Procedural recommendations have been made by pneumological societies including normal values for interpretation of BAL cytology. These normal values derive from small studies in healthy volunteers and have never been analysed for their sensitivity and specificity. OBJECTIVES: This study aims to analyse sensitivity and specificity of these normal values by assessing lavage cell composition in healthy and diseased individuals. METHODS: More than 6000 BAL were retrospectively analysed for their cellular distribution including BALs of 250 healthy individuals. All BALs were obtained under similar conditions. RESULTS: Bronchoalveolar lavage cytology of healthy individuals mirrors data from previous studies with smoking being the most important manipulator of BAL cytology. Analyses of proposed normal values demonstrate specificity between 80% and 95%, whereas sensitivity ranges between 35% and 65%. Using different mathematical models, a value summing up the differences to ATS-proposed normal values of the cytological pattern was found to best discriminate between healthy and diseased individuals with a sensitivity of nearly 60% with a predefined specificity of 95%. CONCLUSION: In summary, our analysis confirmed prior results for healthy volunteers and enlarged these findings by analysing sensitivity and specificity of lavage results in an independent validation cohort of diseased individuals. Thereby, the study may influence the acceptance of BAL in the diagnostic workup of individuals with pulmonary diseases. Additionally, the study proposes a novel value that facilitates lavage interpretation and may therefore be useful in further studies.

Platelets kill bacteria by bridging innate and adaptive immunity via platelet factor 4 and FcγRIIA.

Essentials Human platelets specifically interact with IgG opsonized bacteria through FcγRIIA. Platelet factor 4 (PF4) binds to polyanions (P) and undergoes a conformational change. Anti-PF4/P IgG opsonizes PF4-coated Gram-positive and Gram-negative bacteria. Platelets specifically kill E.coli opsonized with PF4 and human anti-PF4/P IgG. SUMMARY: Background Activated platelets release the chemokine platelet factor 4 (PF4) stored in their granules. PF4 binds to polyanions (P) on bacteria, undergoes a conformational change and exposes neoepitopes. These neoepitopes induce production of anti-PF4/P antibodies. As PF4 binds to a variety of bacteria, anti-PF4/P IgG can bind and opsonize several bacterial species. Objective Here we investigated whether platelets are able to kill bacteria directly after recognizing anti-PF4/P IgG opsonized bacteria in the presence of PF4 via their FcγRIIA. Methods Using platelet-bacteria suspension co-culture experiments and micropatterns with immobilized viable bacteria, in combination with pharmacological inhibitors and human anti- PF4/P IgG we analyzed the role of platelet-mediated killing of bacteria. Results In the presence of PF4, human anti-PF4/P IgG and platelets, E. coli killing (> 50%) with colony forming units (CFU mL-1 ) 0.71 × 104 ± 0.19 was observed compared with controls incubated only with anti-PF4/P IgG (CFU mL-1 3.4 × 104 ± 0.38). Blocking of platelet FcγRIIA using mAb IV.3 (CFU mL-1 2.5 × 104 ± 0.45), or integrin αIIbß3 (CFU mL-1 2.26 × 104 ± 0.31), or disruption of cytoskeletal functions (CFU mL-1 2.7 × 104 ± 0.4) markedly reduced E. coli killing by this mechanism. Our observation of E. coli killing by platelets on micropatterned arrays is compatible with the model that platelets kill bacteria by covering them, actively concentrating them into the area under their granulomere and then releasing antimicrobial substances of platelet α-granules site directed towards bacteria. Conclusion These findings collectively indicate that by bridging of innate and adaptive immune mechanisms, platelets and anti-PF4/polyanion antibodies cooperate in an antibacterial host response.

[Psychosocial Stress, Stress Perception and Stress Management of Students of Social Work: a Quantitative Study]. / Psychosoziale Belastungen, Stressempfinden und Stressbewältigung von Studierenden der Sozialen Arbeit: Ergebnisse einer quantitativen Studie.

In this quantitative study, data on 746 students of social work were collected regarding their current sense of stress, experience of psychosocial drain as well as their use of specific coping strategies. The Perceived Stress Scale (PSS) and the Trier Inventory of Chronic Stress (TICS) were used. The results show that one out of 3 students suffer from a lot of to extreme stress. One-fourth of the students report feeling overworked and socially overburdened. More than half of the students are exposed to psychosocial drain as a consequence of past events in their biography (e. g. death or mental illness of a close relative). Despite these obvious burdens, only one-fourth made use of professional aid or counseling. Students who are primarily using functional coping strategies have a lower sensibility to stress and feel less overworked than students primarily using dysfunctional coping strategies. In the university setting, the theoretically and empirically sound knowledge based on this report can be used profitably: The increasing implementation of seminars on coping with stress at universities itself suggests that learning and utilizing functional coping strategies can contribute to a reduction of stress and strain among students.

Rapid adaptation drives invasion of airway donor microbiota by Pseudomonas after lung transplantation.

In cystic fibrosis (CF) patients, chronic airway infection by Pseudomonas leads to progressive lung destruction ultimately requiring lung transplantation (LT). Following LT, CF-adapted Pseudomonas strains, potentially originating from the sinuses, may seed the allograft leading to infections and reduced allograft survival. We investigated whether CF-adapted Pseudomonas populations invade the donor microbiota and adapt to the non-CF allograft. We collected sequential Pseudomonas isolates and airway samples from a CF-lung transplant recipient during two years, and followed the dynamics of the microbiota and Pseudomonas populations. We show that Pseudomonas invaded the host microbiota within three days post-LT, in association with a reduction in richness and diversity. A dominant mucoid and hypermutator mutL lineage was replaced after 11 days by non-mucoid strains. Despite antibiotic therapy, Pseudomonas dominated the allograft microbiota until day 95. We observed positive selection of pre-LT variants and the appearance of novel mutations. Phenotypic adaptation resulted in increased biofilm formation and swimming motility capacities. Pseudomonas was replaced after 95 days by a microbiota dominated by Actinobacillus. In conclusion, mucoid Pseudomonas adapted to the CF-lung remained able to invade the allograft. Selection of both pre-existing non-mucoid subpopulations and of novel phenotypic traits suggests rapid adaptation of Pseudomonas to the non-CF allograft.

[Clinical classification and initial diagnosis of pulmonary hypertension: recommendations of the Cologne Consensus Conference 2016]. / Klinische Klassifikation der pulmonalen Hypertonie und initiale Diagnostik: Empfehlungen der Kölner Konsensus Konferenz 2016.

The 2015 European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension are also valid for Germany. The guidelines contain detailed information about the clinical classification and diagnosis of pulmonary hypertension, and furthermore provide novel recommendations for risk stratification and follow-up assessments. However, the practical implementation of the European Guidelines in Germany requires the consideration of several country-specific issues and already existing novel data. This requires a detailed commentary to the guidelines, and in some aspects an update already appears necessary. In June 2016, a Consensus Conference organized by the PH working groups of the German Society of Cardiology (DGK), the German Society of Respiratory Medicine (DGP) and the German Society of Pediatric Cardiology (DGPK) was held in Cologne, Germany. This conference aimed to solve practical and controversial issues surrounding the implementation of the European Guidelines in Germany. To this end, a number of working groups was initiated, one of which was specifically dedicated to the clinical classification and initial diagnosis of PH. This article summarizes the results and recommendations of this working group.

[Sarcoidosis]. / Sarkoidose.

Sarcoidosis is a rare granulomatous disease mainly affecting lymph nodes and the lungs but joints, bones, muscles and other organs can also be affected. Sarcoidosis therefore represents an important differential diagnosis to various rheumatic diseases. For the diagnosis and differential diagnostic clarification, bronchoscopy including endobronchial ultrasound-guided fine needle aspiration of mediastinal and hilar lymph nodes represent the main procedures. Because of the high spontaneous remission rate initiating a therapy requires a therapeutic goal defined by sarcoidosis-associated functional organ impairment, especially for acute sarcoidosis. Cortisone represents the most commonly administered medication whereas methotrexate and azathioprine are well-established second-line medications. Antibodies which neutralize tumor necrosis factors (TNF) are a potential third-line therapy.

[Diagnosis and treatment of sarcoidosis. Current standards]. / Diagnostik und Therapie der Sarkoidose. Was ist gesichert?

Sarcoidosis is a granulomatous disease that mainly affects the lungs and intrathoracic lymph nodes; however, virtually any organ can be affected. As an orphan disease, recommendations are mainly based on observational or small randomized studies as well as experts' opinion. Diagnosing sarcoidosis requires proof of non-necrotizing granulomas in patients with a compatible symptomatic pattern and the exclusion of other granulomatous diseases. Granulomas can be detected best in the lungs or intrathoracic lymph nodes. Therefore, bronchoscopy and endobronchial ultrasound with biopsies of lymph nodes are the major tools to diagnose sarcoidosis. Frequently, close follow-up and symptomatic therapy are sufficient to allow for spontaneous resolution. In case of functional organ impairment, cardial or CNS involvement, or other complications, steroid therapy is necessary with a starting dose of 0.5 mg/kg body weight that should be tapered-off over 6-12 months. Steroid-refractory disease can be treated by adding methotrexate or azathioprine, two drugs long known in sarcoidosis treatment. Monoclonal antibodies against TNF and lung transplantation are further therapeutic options.

Multicentre study of abdominal aortic aneurysm measurement and enlargement.

BACKGROUND: No effective treatment is currently available to prevent progression of small and medium-sized abdominal aortic aneurysms (AAAs). Identification of drugs with sufficient promise to justify large expensive randomized trials remains challenging. One potentially useful strategy is to look for associations between commonly used drugs and AAA enlargement in appropriately adjusted observational studies. METHODS: Potential AAA measurements were identified from abdominal imaging reports in the electronic data files of three medical centres from 1995 to 2010. AAA measurements were extracted manually and patients with an aneurysm of 3 cm or larger, who had at least two measurements over an interval of at least 6 months, were identified. Other data were obtained from the electronic data files (demographics, co-morbidities, smoking status, drug use) to conduct a propensity analysis of the associations of drugs and other factors with AAA enlargement. RESULTS: From 52,962 abdominal imaging studies, 5362 patients with an AAA of 3 cm or more were identified, of whom 2428 had at least two measurements over at least 6 months. Mean AAA follow-up was 3.4 years and the mean AAA enlargement rate was 2.0 mm per year. Propensity analysis demonstrated no significant association of AAA enlargement with statins, beta-blockers, angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers. Diabetes was associated with a reduction in AAA enlargement of 1.2 mm per year (P = 0.008), and chronic obstructive pulmonary disease was associated with increased enlargement (0.5 mm per year; P = 0.050). Moderate AAA measurement variation and substantial terminal digit preference were also observed, but the digit preference became less pronounced after 2000. CONCLUSION: This study confirms the negative association of diabetes with AAA progression. There was no evidence that commonly used cardiovascular drugs affect AAA enlargement.