Pathogen-specific antibody profiles in patients with severe systemic infections.

Infections are often caused by pathobionts, endogenous bacteria that belong to the microbiota. Trauma and surgical intervention can allow bacteria to overcome host defences, ultimately leading to sepsis if left untreated. One of the main defence strategies of the immune system is the production of highly specific antibodies. In the present proof-of-concept study, plasma antibodies against 9 major pathogens were measured in sepsis patients, as an example of severe systemic infections. The binding of plasma antibodies to bacterial extracellular proteins was quantified using a semi-automated immunoblot assay. Comparison of the pathogen-specific antibody levels before and after infection showed an increase in plasma IgG in 20 out of 37 tested patients. This host-directed approach extended the results of pathogen-oriented microbiological and PCR diagnostics: a specific antibody response to additional bacteria was frequently observed, indicating unrecognised poly-microbial invasion. This might explain some cases of failed, seemingly targeted antibiotic treatment.

Psychosocial and physical long-term outcome in patients with a history of takotsubo cardiomyopathy or myocardial infarction - a multi-centered case control study.

Physical long-term impacts of Takotsubo Cardiomyopathy (TTC) remain controversial and an underestimation of their severity becomes increasingly evident. Even less is known about mental long-term impacts of TTC. This study aims at a better understanding of the physical and mental long-term effects of TTC in comparison to myocardial infarctions (MI). On average 5 years after disease onset, 68 TTC patients and 68 age- and sex-matched MI patients were assessed for disease-related quality of life, depression, anxiety, chronic stress, social support, resilience, and life events prior to disease onset. Scores of TTC and MI patients were compared to each other and to normative references values. Regression analyses were used to evaluate the predictive value of the number of life events prior to disease onset for physical and mental long-term outcomes. Both groups displayed higher scores in depression and anxiety, higher levels of chronic stress, and lower scores in physical and mental quality of life in comparison to norm samples, while social support did not differ from norms. No differences between the two patient groups were observed. Within both groups, the majority of patients (TTC: 69.1%; MI: 60.3%) reported stressful life events prior to disease onset. In TTCs and MIs, the number of events had a significant impact on long-term mental health and chronic stress. Notably, both patient collectives scored higher in resilience than healthy controls. Results suggest negative long-term impacts of TTC on mental and physical wellbeing, comparable to those of MI. Besides a good somatic-medical care, psychotherapeutic support, including the development of functional coping strategies, might be warranted for TTC patients. The long-term impact of TTC should be taken as serious as that of MI.

Continuing chronic beta-blockade in the acute phase of severe sepsis and septic shock is associated with decreased mortality rates up to 90 days.

BACKGROUND: There is growing evidence that beta-blockade may reduce mortality in selected patients with sepsis. However, it is unclear if a pre-existing, chronic oral beta-blocker therapy should be continued or discontinued during the acute phase of severe sepsis and septic shock. METHODS: The present secondary analysis of a prospective observational single centre trial compared patient and treatment characteristics, length of stay and mortality rates between adult patients with severe sepsis or septic shock, in whom chronic beta-blocker therapy was continued or discontinued, respectively. The acute phase was defined as the period ranging from two days before to three days after disease onset. Multivariable Cox regression analysis was performed to compare survival outcomes in patients with pre-existing chronic beta-blockade. RESULTS: A total of 296 patients with severe sepsis or septic shock and pre-existing, chronic oral beta-blocker therapy were included. Chronic beta-blocker medication was discontinued during the acute phase of sepsis in 129 patients and continued in 167 patients. Continuation of beta-blocker therapy was significantly associated with decreased hospital (P=0.03), 28-day (P=0.04) and 90-day mortality rates (40.7% vs 52.7%; P=0.046) in contrast to beta-blocker cessation. The differences in survival functions were validated by a Log-rank test (P=0.01). Multivariable analysis identified the continuation of chronic beta-blocker therapy as an independent predictor of improved survival rates (HR = 0.67, 95%-CI (0.48, 0.95), P=0.03). CONCLUSIONS: Continuing pre-existing chronic beta-blockade might be associated with decreased mortality rates up to 90 days in septic patients.

How empathic is your healthcare practitioner? A systematic review and meta-analysis of patient surveys.

BACKGROUND: A growing body of evidence suggests that healthcare practitioners who enhance how they express empathy can improve patient health, and reduce medico-legal risk. However we do not know how consistently healthcare practitioners express adequate empathy. In this study, we addressed this gap by investigating patient rankings of practitioner empathy. METHODS: We conducted a systematic review and meta-analysis of studies that asked patients to rate their practitioners' empathy using the Consultation and Relational Empathy (CARE) measure. CARE is emerging as the most common and best-validated patient rating of practitioner empathy. We searched: MEDLINE, Embase, PsycINFO, Cinahl, Science & Social Science Citation Indexes, the Cochrane Library and PubMed from database inception to March 2016. We excluded studies that did not use the CARE measure. Two reviewers independently screened titles and extracted data on average CARE scores, demographic data for patients and practitioners, and type of healthcare practitioners. RESULTS: Sixty-four independent studies within 51 publications had sufficient data to pool. The average CARE score was 40.48 (95% CI, 39.24 to 41.72). This rank s in the bottom 5th percentile in comparison with scores collected by CARE developers. Longer consultations (n = 13) scored 15% higher (42.60, 95% CI 40.66 to 44.54) than shorter (n = 9) consultations (34.93, 95% CI 32.63 to 37.24). Studies with mostly (>50%) female practitioners (n = 6) showed 16% higher empathy scores (42.77, 95% CI 38.98 to 46.56) than those with mostly (>50%) male (n = 6) practitioners (34.84, 95% CI 30.98 to 38.71). There were statistically significant (P = 0.032) differences between types of providers (allied health professionals, medical students, physicians, and traditional Chinese doctors). Allied Health Professionals (n = 6) scored the highest (45.29, 95% CI 41.38 to 49.20), and physicians (n = 39) scored the lowest (39.68, 95% CI 38.29 to 41.08). Patients in Australia, the USA, and the UK reported highest empathy ratings (>43 average CARE), with lowest scores (<35 average CARE scores) in Hong Kong. CONCLUSIONS: Patient rankings of practitioner empathy are highly variable, with female practitioners expressing empathy to patients more effectively than male practitioners. The high variability of patient rating of practitioner empathy is likely to be associated with variable patient health outcomes. Limitations included frequent failure to report response rates introducing a risk of response bias. Future work is warranted to investigate ways to reduce the variability in practitioner empathy.

Cold atmospheric pressure plasma for treatment of chronic wounds: drug or medical device?

OBJECTIVE: The use of cold atmospheric pressure plasma (CAPP) as a new therapeutic option to aid the healing of chronic wounds appears promising. Currently, uncertainty exists regarding their classification as medical device or medical drug. Because the classification of CAPP has medical, legal, and economic consequences as well as implications for the level of preclinical and clinical testing, the correct classification is not an academic exercise, but an ethical need. METHOD: A multidisciplinary team of physicians, surgeons, pharmacists, physicists and lawyers has analysed the physical and technical characteristics as well as legal conditions of the biological action of CAPP. RESULTS: It was concluded that the mode of action of the locally generated CAPP, with its main active components being different radicals, is pharmacological and not physical in nature. CONCLUSION: Depending on the intended use, CAPP should be classified as a drug, which is generated by use of a medical device directly at the point of therapeutic application.

[Placebo and nocebo : How can they be used or avoided?] / Placebo und Nocebo : Wie einsetzen bzw. vermeiden?

The expectations of patients enhance the probability of their occurrence and are thereby the main triggers for inducing placebo and nocebo responses. Strong placebo effects are not only regularly observed in pharmaceutical and non-pharmaceutical sham treatment in placebo controlled studies but also make a considerable contribution to any real treatment. The accompanying words are essential to ensure maximum impact of drugs and other forms of treatment. They should contain positive expressions instead of negations. Such a strengthening of drug therapy by placebo effects is more important than the widespread use of placebos that remains a problem because of the obligation to provide information and effective therapy and because of inherently induced side effects. Any false comments about symptoms or side effects can aggravate or induce them. Nocebo effects are not imagined but real symptoms that can definitely be harmful. They constitute a considerable proportion of the side effects requiring treatment. Awareness and knowledge is needed to prevent or neutralize them. Nocebo effects are avoidable when risk information is always directly combined with positive aspects, such as the expected benefits of the treatment or the prophylactic measures and therapeutic options for side effects. Existing negative expectations are disrupted by providing more alternative options and by leaving negative experiences in the past where they belong. Placebo and nocebo effects are strongly sensitive to the context. They are dependent on the experiences and conceptions of the individual patient, as well as on the physician-patient relationship. The latter can provide the best protection against harm from risk disclosure. In addition, the expectations of patients and their consequences are strongly affected by the expectations of the treating doctor, by fellow patients, the media and society.

Acute renal response to changes in carbon dioxide in mechanically ventilated female pigs.

Kidney response to acute and mechanically induced variation in ventilation associated with different levels of PEEP has not been investigated. We aimed to quantify the effect of ventilatory settings on renal acid-base compensation. Forty-one pigs undergoing hypo- (<0.2 Lkg-1 min-1, PEEP 25 cmH2O), intermediate (0.2-0.4 Lkg-1 min-1 with either PEEP 5 or 25 cmH2O), or hyper-ventilation (>0.4 Lkg-1 min-1, PEEP 5 cmH2O) for 48 h were retrospectively included. The decrease in pH paralleled the decrease in plasma strong ion difference (SID) in hyper- and intermediately ventilated groups with lower PEEP. In contrast, the plasma SID remained nearly constant in hypo- and intermediately ventilated groups with higher PEEP. Changes in plasma chloride concentration accounted for the changes in plasma SID (conditional R2 = 0.86). The plasma SID changes were paralleled by mirror changes in urinary SID. Higher PEEP (25 cmH2O), compared to lower PEEP (5 cmH2O) dampened or abolished the renal compensation through its effect on hemodynamics (higher central venous and mean pulmonary pressures), irrespective of minute ventilation. During mechanical ventilation, the compensatory renal response to respiratory derangement is immediate and progressive but can be dampened by high PEEP levels.

[The first COVID-19 hotspot in a retirement home in Hamburg]. / Der erste COVID-19-Hotspot in einer Hamburger Senioreneinrichtung: Präventionskonzept, Letalität und Obduktionsbefunde.

Background: Coronavirus disease 2019 (COVID-19), a disease caused by the new coronavirus (SARS-CoV-2), is a particular threat to old people. At the end of March 2020, the first and so far largest outbreak of the disease occurred in a retirement home in Hamburg. Methods: Analysis of procedures in dealing with a residential unit affected by SARS-CoV­2, accommodating a risk group of 60 seniors with dementia is presented as well as a detailed presentation of post-mortem examination results of all 8 deceased tested positive for SARS-CoV­2. Results: Out of 60 residents, 39 were infected by SARS-CoV­2. Due to preventive procedures it was possible to stop further spreading of the infection to other residential areas. In all 8 fatal cases, the autopsy diagnosis was death due to COVID-19. Autopsies revealed all COVID-19 patients to have a fatal (broncho)pneumonia and signs of relevant pre-existing cardiac, renal and pulmonary conditions in all cases. In 75% (n = 6) of the cases a fresh venous thrombosis was found. In 66.7% (n = 4) of the cases thrombotic events were combined with peripheral pulmonary artery thromboembolisms. Conclusion: The cohort of SARS-CoV­2 infected residents of a nursing home is characteristic for clinical and epidemiological features of the new coronavirus disease. Due to a centralized evaluation of all fatalities at the Institute of Legal Medicine in Hamburg, a detailed examination of all deceased positive for SARS-CoV­2 was possible. Thereby, increased case fatality rates of approximately 20% could in all cases be assigned to a relevant number of pre-existing comorbidities of multiple organ systems, which was consistent with the clinical data available.

Cortisol levels predict motion sickness tolerance in women but not in men.

A variety of intrinsic and extrinsic factors contribute to motion sickness severity in a stressful motion environment. The interplay of all these factors may partially explain the high inter-subject variability of motion sickness susceptibility found in many studies as well as some of the contradictory findings between studies regarding the modulating influence of single factors. We investigated the role of endogenous cortisol levels, gender and repetitive experience for motion sickness susceptibility. Motion sickness was induced in 32 healthy, but motion-sickness susceptible volunteers (16:16 males:females), by means of a vection drum. Subjects were investigated between 8:00 am (high cortisol) and 11:00 am (low cortisol), and on five consecutive days. Tolerance to rotation (RT) of the drum, motion sickness symptom ratings (SR) and salivary cortisol levels were assessed. Baseline cortisol levels correlated positively with RT in women, but not in men. RT showed a gender-specific time course across days, with higher values in males than in females on day 1, and sensitization on day 3 only in men. SR and cortisol levels following rotation did not differ between males and females, or between testing days. Gender differences in motion sickness susceptibility appear to be linked to a different role of basal cortisol levels for motion sickness tolerance. Results clearly indicate the need to control for gender, day time and cortisol levels in studies of motion sickness.