'Better see a doctor?' Status quo of symptom checker apps in Germany: A cross-sectional survey with a mixed-methods design (CHECK.APP).

Background: Symptom checker apps (SCAs) offer symptom classification and low-threshold self-triage for laypeople. They are already in use despite their poor accuracy and concerns that they may negatively affect primary care. This study assesses the extent to which SCAs are used by medical laypeople in Germany and which software is most popular. We examined associations between satisfaction with the general practitioner (GP) and SCA use as well as the number of GP visits and SCA use. Furthermore, we assessed the reasons for intentional non-use. Methods: We conducted a survey comprising standardised and open-ended questions. Quantitative data were weighted, and open-ended responses were examined using thematic analysis. Results: This study included 850 participants. The SCA usage rate was 8%, and approximately 50% of SCA non-users were uninterested in trying SCAs. The most commonly used SCAs were NetDoktor and Ada. Surprisingly, SCAs were most frequently used in the age group of 51-55 years. No significant associations were found between SCA usage and satisfaction with the GP or the number of GP visits and SCA usage. Thematic analysis revealed skepticism regarding the results and recommendations of SCAs and discrepancies between users' requirements and the features of apps. Conclusion: SCAs are still widely unknown in the German population and have been sparsely used so far. Many participants were not interested in trying SCAs, and we found no positive or negative associations of SCAs and primary care.

COVID-19 Outcomes in Kidney Transplant Recipients in a German Transplant Center.

Kidney transplant recipients (KTRs) show higher morbidity and mortality from COVID-19 than the general population and have an impaired response to vaccination. We analyzed COVID-19 incidence and clinical outcomes in a single-center cohort of approximately 2500 KTRs. Between 1 February 2020 and 1 July 2022, 578 KTRs were infected with SARS-CoV-2, with 25 (4%) recurrent infections. In total, 208 KTRs (36%) were hospitalized, and 39 (7%) died. Among vaccinated patients, infection with the Omicron variant had a mortality of 2%. Unvaccinated patients infected with the Omicron variant showed mortality (9% vs. 11%) and morbidity (hospitalization 52% vs. 54%, ICU admission 12% vs. 18%) comparable to the pre-Omicron era. Multivariable analysis revealed that being unvaccinated (OR = 2.15, 95% CI [1.38, 3.35]), infection in the pre-Omicron era (OR = 3.06, 95% CI [1.92, 4.87]), and higher patient age (OR = 1.04, 95% CI [1.03, 1.06]) are independent risk factors for COVID-19 hospitalization, whereas a steroid-free immunosuppressive regimen was found to reduce the risk of COVID-19 hospitalization (OR = 0.51, 95% CI [0.33, 0.79]). This suggests that both virological changes in the Omicron variant and vaccination reduce the risk for morbidity and mortality from COVID-19 in KTRs. Our data extend the knowledge from the general population to KTRs and provide important insights into outcomes during the Omicron era.

Risk Factors for Hepatitis E Virus Infection and Eating Habits in Kidney Transplant Recipients.

There is a significant risk for ongoing and treatment-resistant courses of hepatitis E virus (HEV) infection in patients after solid organ transplantation. The aim of this study was to identify risk factors for the development of hepatitis E, including the dietary habits of patients. We conducted a retrospective single-center study with 59 adult kidney and combined kidney transplant recipients who were diagnosed with HEV infection between 2013 and 2020. The outcomes of HEV infections were analyzed during a median follow-up of 4.3 years. Patients were compared with a control cohort of 251 transplant patients with elevated liver enzymes but without evidence of an HEV infection. Patients' alimentary exposures during the time before disease onset or diagnosis were assessed. Previous intense immunosuppression, especially treatment with high-dose steroids and rituximab, was a significant risk factor to acquire hepatitis E after solid organ transplantation. Only 11 out of 59 (18.6%) patients reached remission without further ribavirin (RBV) treatment. A total of 48 patients were treated with RBV, of which 19 patients (39.6%) had either viral rebounds after the end of treatment or did not reach viral clearance at all. Higher age (>60 years) and a BMI ≤ 20 kg/m2 were risk factors for RBV treatment failure. Deterioration in kidney function with a drop in eGFR (p = 0.046) and a rise in proteinuria was more common in patients with persistent hepatitis E viremia. HEV infection was associated with the consumption of undercooked pork or pork products prior to infection. Patients also reported processing raw meat with bare hands at home more frequently than the controls. Overall, we showed that the intensity of immunosuppression, higher age, a low BMI and the consumption of undercooked pork meat correlated with the development of hepatitis E.

Intraprocedural gastric juice analysis as compared to rapid urease test for real-time detection of Helicobacter pylori.

BACKGROUND: Endofaster is an innovative technology that can be combined with upper gastrointestinal endoscopy (UGE) to perform gastric juice analysis and real-time detection of Helicobacter pylori (H. pylori). AIM: To assess the diagnostic performance of this technology and its impact on the management of H. pylori in the real-life clinical setting. METHODS: Patients undergoing routine UGE were prospectively recruited. Biopsies were taken to assess gastric histology according to the updated Sydney system and for rapid urease test (RUT). Gastric juice sampling and analysis was performed using the Endofaster, and the diagnosis of H. pylori was based on real-time ammonium measurements. Histological detection of H. pylori served as the diagnostic gold standard for comparing Endofaster-based H. pylori diagnosis with RUT-based H. pylori detection. RESULTS: A total of 198 patients were prospectively enrolled in an H. pylori diagnostic study by Endofaster-based gastric juice analysis (EGJA) during the UGE. Biopsies for RUT and histological assessment were performed on 161 patients (82 men and 79 women, mean age 54.8 ± 19.2 years). H. pylori infection was detected by histology in 47 (29.2%) patients. Overall, the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value (NPV) for H. pylori diagnosis by EGJA were 91.5%, 93.0%, 92.6%, 84.3%, and 96.4%, respectively. In patients on treatment with proton pump inhibitors, diagnostic sensitivity was reduced by 27.3%, while specificity and NPV were unaffected. EGJA and RUT were comparable in diagnostic performance and highly concordant in H. pylori detection (κ-value = 0.85). CONCLUSION: Endofaster allows for rapid and highly accurate detection of H. pylori during gastroscopy. This may guide taking additional biopsies for antibiotic susceptibility testing during the same procedure and then selecting an individually tailored eradication regimen.

Pregnancy after Kidney Transplantation-Impact of Functional Renal Reserve, Slope of eGFR before Pregnancy, and Intensity of Immunosuppression on Kidney Function and Maternal Health.

Women of childbearing age show increased fertility after kidney transplantation. Of concern, preeclampsia, preterm delivery, and allograft dysfunction contribute to maternal and perinatal morbidity and mortality. We performed a retrospective single-center study, including 40 women with post-transplant pregnancies after single or combined pancreas-kidney transplantation between 2003 and 2019. Outcomes of kidney function up to 24 months after the end of pregnancy were compared with a matched-pair cohort of 40 transplanted patients without pregnancies. With a maternal survival rate of 100%, 39 out of 46 pregnancies ended up with a live-born baby. The eGFR slopes to the end of 24 months follow-up showed mean eGFR declines in both groups (-5.4 ± 14.3 mL/min in pregnant versus -7.6 ± 14.1 mL/min in controls). We identified 18 women with adverse pregnancy events, defined as preeclampsia with severe end-organ dysfunction. An impaired hyperfiltration during pregnancy was a significant risk contributor for both adverse pregnancy events (p < 0.05) and deterioration of kidney function (p < 0.01). In addition, a declining renal allograft function in the year before pregnancy was a negative predictor of worsening allograft function after 24 months of follow-up. No increased frequency of de novo donor-specific antibodies after delivery could be detected. Overall, pregnancies in women after kidney transplantation showed good allograft and maternal outcomes.

Shear wave elastography-based liver fibrosis assessment in patients with chronic hepatitis E displays elevated liver stiffness regardless of previous antiviral therapy.

Background: Hepatitis E virus (HEV) infection especially in immunocompromised individuals can lead to chronic hepatitis. Aggressive courses of chronic hepatitis E leading to liver cirrhosis in a short period of time have been described, but evidence on the degree of liver involvement in chronic hepatitis E is rare. We therefore aimed to quantify liver fibrosis in patients with chronic active hepatitis E compared to patients with sustained virological response after ribavirin (RBV) treatment using 2D-shear wave elastography (2D-SWE) to measure liver stiffness. Methods: Patients with chronic hepatitis E underwent 2D-SWE, B-mode and Doppler ultrasound and laboratory testing in order to assess severity of liver involvement. Results: In this cross-sectional study, we included 14 patients of whom 8 had ongoing chronic hepatitis E and 6 patients had been successfully treated for chronic hepatitis E. The most frequent cause for immunosuppression was prior kidney transplantation (n=12), one patient was a multivisceral transplant recipient, one had been treated for lymphoma. Five patients cleared HEV after RBV therapy, one patient reached viral clearance after reduction of his immunosuppressive medication. Using 2D-SWE measurement, 71.4% displayed increased stiffness indicative of liver fibrosis: 57.1% classified as significant fibrosis and 14.3% as severe fibrosis. Liver stiffness did not differ between patients with active chronic hepatitis E and in patients who had cleared HEV (1.59 and 1.54 m/s respectively). Compared with a control group of kidney transplant recipients without hepatitis E (1.44 m/s), the patients with a history of hepatitis E displayed a significantly higher liver stiffness (P=0.04). Conclusions: In our cohort of chronic hepatitis E patients, elevated liver stiffness indicating liver fibrosis was common and significantly higher than in controls. This is consistent with prior sparse reports of the presence of liver fibrosis or cirrhosis in chronic hepatitis E and emphasizes the need for HEV testing, therapy and research on new therapeutic options. As elevated liver stiffness was also present in patients after HEV treatment, continuous liver surveillance including elastography and ultrasound should be considered.

Declining Course of Humoral Immune Response in Initially Responding Kidney Transplant Recipients after Repeated SARS-CoV-2 Vaccination.

The immunogenicity of SARS-CoV-2 vaccines in kidney transplant recipients is limited, resulting in inadequately low serological response rates and low immunoglobulin (Ig) levels, correlating with reduced protection against death and hospitalization from COVID-19. We retrospectively examined the time course of anti-SARS-CoV-2 Ig antibody levels after up to five repeated vaccinations in 644 previously nonresponding kidney transplant recipients. Using anti SARS-CoV-2 IgG/IgA ELISA and the total Ig ECLIA assays, we compared antibody levels at 1 month with levels at 2 and 4 months, respectively. Additionally, we correlated the measurements of the used assays. Between 1 and 2 months, and between 1 and 4 months, mean anti-SARS-CoV-2 Ig levels in responders decreased by 14% and 25%, respectively, depending on the assay. Absolute Ig values and time course of antibody levels showed high interindividual variability. Ig levels decreased by at least 20% in 77 of 148 paired samples with loss of sufficient serological protection over time occurring in 18 out of 148 (12.2%). IgG ELISA and total Ig ECLIA assays showed a strong positive correlation (Kendall's tau = 0.78), yet the two assays determined divergent results in 99 of 751 (13.2%) measurements. IgG and IgA assays showed overall strong correlation but divergent results in 270 of 1.173 (23.0%) cases and only weak correlation of antibody levels in positive samples. Large interindividual variability and significant loss of serological response after 4 months supports repeated serological sampling and consideration of shorter vaccination intervals in kidney transplant recipients.

Serological Response to Three, Four and Five Doses of SARS-CoV-2 Vaccine in Kidney Transplant Recipients.

Mortality from COVID-19 among kidney transplant recipients (KTR) is high, and their response to three vaccinations against SARS-CoV-2 is strongly impaired. We retrospectively analyzed the serological response of up to five doses of the SARS-CoV-2 vaccine in KTR from 27 December 2020 until 31 December 2021. Particularly, the influence of the different dose adjustment regimens for mycophenolic acid (MPA) on serological response to fourth vaccination was analyzed. In total, 4277 vaccinations against SARS-CoV-2 in 1478 patients were analyzed. Serological response was 19.5% after 1203 basic immunizations, and increased to 29.4%, 55.6%, and 57.5% in response to 603 third, 250 fourth, and 40 fifth vaccinations, resulting in a cumulative response rate of 88.7%. In patients with calcineurin inhibitor and MPA maintenance immunosuppression, pausing MPA and adding 5 mg prednisolone equivalent before the fourth vaccination increased the serological response rate to 75% in comparison to the no dose adjustment (52%) or dose reduction (46%). Belatacept-treated patients had a response rate of 8.7% (4/46) after three vaccinations and 12.5% (3/25) after four vaccinations. Except for belatacept-treated patients, repeated SARS-CoV-2 vaccination of up to five times effectively induces serological response in kidney transplant recipients. It can be enhanced by pausing MPA at the time of vaccination.

Predictors of Serological Response to SARS-CoV-2 Vaccination in Kidney Transplant Patients: Baseline Characteristics, Immunosuppression, and the Role of IMPDH Monitoring.

Immunosuppression increases the risk of severe coronavirus disease 2019 (COVID-19). Morbidity and mortality of this disease in kidney transplant patients are higher than in the general population. As the vaccination response of transplant patients is weak, serological monitoring was performed. In this cohort study, we analyzed the determinants of vaccination response. All patients had no history of COVID-19. With anti-spike IgG monitoring, 148 responders and 415 non-responders were identified. We compared both groups using multivariate analyses of the cohort and a sub-cohort of mycophenolic-acid-treated patients. We investigated the influence of patient characteristics, immunosuppression, and erythrocyte inosine monophosphate dehydrogenase (IMPDH) activity. In responders, the time after transplantation was longer (13.5 vs. 8.5 years), the glomerular filtration rate was higher (56.9 vs. 47.8 mL/min/1.73 m2), and responders were younger (53.0 vs. 57.4 years). Heterologous vaccination was more effective than homologous vaccination. Calcineurin inhibitors plus mycophenolate reduced the seroconversion rate. No seroconversion was observed in belatacept patients. In mycophenolate-treated patients, IMPDH activity was a significantly better predictor of response than mycophenolate dose (AUC 0.84 vs. 0.62, p < 0.001). Immunosuppression strongly affects vaccine response. Modifications to immunosuppression should be considered in order to facilitate this response. Erythrocyte IMPDH activity can be used to guide mycophenolate treatment.

Temporary antimetabolite treatment hold boosts SARS-CoV-2 vaccination-specific humoral and cellular immunity in kidney transplant recipients.

Transplant recipients exhibit an impaired protective immunity after SARS-CoV-2 vaccination, potentially caused by mycophenolate (MPA) immunosuppression. Recent data from patients with autoimmune disorders suggest that temporary MPA hold might greatly improve booster vaccination outcomes. We applied a fourth dose of SARS-CoV-2 vaccine to 29 kidney transplant recipients during a temporary (5 weeks) MPA/azathioprine hold, who had not mounted a humoral immune response to previous vaccinations. Seroconversion until day 32 after vaccination was observed in 76% of patients, associated with acquisition of virus-neutralizing capacity. Interestingly, 21/25 (84%) calcineurin inhibitor-treated patients responded, but only 1/4 belatacept-treated patients responded. In line with humoral responses, counts and relative frequencies of spike receptor binding domain-specific (RBD-specific) B cells were markedly increased on day 7 after vaccination, with an increase in RBD-specific CD27++CD38+ plasmablasts. Whereas overall proportions of spike-reactive CD4+ T cells remained unaltered after the fourth dose, frequencies were positively correlated with specific IgG levels. Importantly, antigen-specific proliferating Ki67+ and in vivo-activated programmed cell death 1-positive T cells significantly increased after revaccination during MPA hold, whereas cytokine production and memory differentiation remained unaffected. In summary, antimetabolite hold augmented all arms of immunity during booster vaccination. These data suggest further studies of antimetabolite hold in kidney transplant recipients.

Caffeine and Its Pharmacological Benefits in the Management of Androgenetic Alopecia: A Review.

Caffeine, particularly after ingestion, is well known to exert various pharmacological effects. A growing body of evidence implicates the ingestion of caffeine with beneficial effects on several diseases. The easy penetration of caffeine across the skin barrier and into human skin makes caffeine an ideal compound for topical application. Hair loss is known to negatively affect the quality of life and predispose to depression and anxiety. Androgenetic alopecia (AGA) is the most common type of hair loss in both men and women. To date, only few approved drug-based treatments for AGA exist, and these are inevitably associated with side effects. Therefore, the development of topical treatments based on well-tolerated natural ingredients such as caffeine to alleviate hair loss may provide a much-needed alternative to drug-based approaches.

The active bacterial assemblages of the upper GI tract in individuals with and without Helicobacter infection.

OBJECTIVE: Patients infected with Helicobacter pylori develop chronic gastritis with a subgroup progressing to further complications. The role of microbiota from the oral cavity swallowed with saliva and either transiting the stomach or persisting in the gastric mucosa is uncertain. It is also not known whether the bacterial community differs in luminal and mucosal niches. A key question is whether H. pylori influences the bacterial communities of gastroduodenal niches. DESIGN: Saliva, gastric and duodenal aspirates as well as gastric and duodenal biopsies were collected during oesophagogastroduodenoscopy from 24 patients (m:9, f:15, mean age 52.2±SD 14.5 years). RNA was extracted and the V1-V2 region of the retrotranscribed bacterial 16S rRNA amplified and sequenced on the Illumina MiSeq platform. RESULTS: Overall, 687 bacterial phylotypes that belonged to 95 genera and 11 phyla were observed. Each individual comprised a unique microbiota composition that was consistent across the different niches. However, the stomach fluid enriched for specific microbiota components. Helicobacter spp were shown to dominate the mucosa-associated community in the stomach, and to significantly influence duodenal and oral communities. CONCLUSIONS: The detailed analysis of the active global bacterial communities from the five distinct sites of the upper GI tract allowed for the first time the differentiation between host effects and the influence of sampling region on the bacterial community. The influence of Helicobacter spp on the global community structures is striking.

Determination of nasal and oropharyngeal microbiomes in a multicenter population-based study - findings from Pretest 1 of the German National Cohort.

We examined acceptability, preference and feasibility of collecting nasal and oropharyngeal swabs, followed by microbiome analysis, in a population-based study with 524 participants. Anterior nasal and oropharyngeal swabs were collected by certified personnel. In addition, participants self-collected nasal swabs at home four weeks later. Four swab types were compared regarding (1) participants' satisfaction and acceptance and (2) detection of microbial community structures based on deep sequencing of the 16 S rRNA gene V1-V2 variable regions. All swabbing methods were highly accepted. Microbial community structure analysis revealed 846 phylotypes, 46 of which were unique to oropharynx and 164 unique to nares. The calcium alginate tipped swab was found unsuitable for microbiome determinations. Among the remaining three swab types, there were no differences in oropharyngeal microbiomes detected and only marginal differences in nasal microbiomes. Microbial community structures did not differ between staff-collected and self-collected nasal swabs. These results suggest (1) that nasal and oropharyngeal swabbing are highly feasible methods for human population-based studies that include the characterization of microbial community structures in these important ecological niches, and (2) that self-collection of nasal swabs at home can be used to reduce cost and resources needed, particularly when serial measurements are to be taken.

Mercury concentrations in feathers of Common Swifts (Apus apus).

Mercury (Hg) has been well studied as a bioaccumulated contaminant in aquatic ecosystems worldwide. It has been found to have negative effects on carnivorous and piscivorous bird species with the highest Hg concentrations at the top of the food chain. The objective of this study was to increase our knowledge of mercury exposure in insectivorous birds, especially in a species of the family Apodidae. The Common Swift (Apus apus) that specialises on feeding on aerial plankton molts and winters as a long-distance migrant in Sub-Saharan Africa. In the breeding seasons 2011-2013 the concentrations of Hg in primary flight feathers (P8-P10) in juvenile (n = 35) and adult (n = 25) injured Common Swifts were examined in the area of Hannover, Lower Saxony, Germany using cold vapour atomic absorption spectrometry. As a first reference, it was possible to determine feather Hg levels in adult (Mean ± SD: 0.53 mg/kg wet weight ± 0.37; Xmin-Xmax: 0.04-1.45 mg/kg; n = 25) as well as in juvenile Swifts (Mean ± SD: 0.11 mg/kg wet weight ± 0.06; Xmin-Xmax: 0.04-0.25 mg/kg; n = 35). The significant differences between the ages (p ≤ 0.001) are probably caused by differences in the feather growth, in accumulation of mercury for a longer time in adults as well as particularly in differences between mercury pollution in breeding and wintering ground. The mercury levels detected in swifts in this study are all below the range found by other authors to cause behavioural changes or reduced reproduction (5 mg/kg).

H. pylori and its modulation of gastrointestinal microbiota.

The discovery of Helicobacter pylori (H. pylori) changed the dogma of the stomach as a sterile organ. H. pylori is an obligate pathogen in the human stomach and recognized as a definite carcinogen. Extensive research on the interaction of this bacterium with the gastric mucosa has been performed over the past three decades. The development of new nucleotide sequencing techniques and new biocomputational tools has opened the field for studying the diversity and complexity of the microbiome in the gastrointestinal tract independently of cultural methods. These techniques allow to better characterize further gastric bacteria. However, the differentiation of alive resident and transient microbes requires an analysis beyond the pure detection of bacterial genomic material applying a combination with metabolomic analyses. Currently, the interaction of gastric microbiota with each other, with H. pylori and with the host is addressed by extensive research. This review gives a concise overview on current knowledge on this topic.

Simple proposal for dosimetry with an Elekta iViewGT™ electronic portal imaging device (EPID) using commercial software modules.

BACKGROUND: An electronic portal imaging device (EPID) is used to control for patient setup and positioning during fractionated radiotherapy. Due to the rising complexity and conformity of irradiation techniques, the demand for an accurate verification of the dose delivered to the patient has also increased. The purpose of this study was to investigate a simple guidance for dosimetry with an Elekta iViewGT™ EPID using commercial software modules. MATERIAL AND METHODS: EPID measurements were performed using an Elekta iViewGT™ EPID on a linear accelerator with 6 MV x-ray beam. The EPID signal was studied for reproducibility, as well as characteristics as a function of dose, dose rate, and field size. A series of experiments, comparing the response of the flat panel imager and ionization chamber measurements of dose, determine the parameters for the calibration model. EPID measurements were also compared with calculations of the treatment planning system. RESULTS: We found a stable response of the EPID signal over a period of 14 months. It showed nonlinearity depending on dose up to 6.8%. There were low oscillations up to 1.2% depending on dose rate. For all fields, the calibrated flat panel profiles match the measured and calculated dose profiles with maximum deviation of 2-3% for the in-field region. In the high gradient areas, higher differences up to 6% were found. CONCLUSIONS: The gamma evaluation indicates good correlation between predicted and acquired EPID images. The EPID-based pretreatment IMRT verification method will help to improve the quality assurance procedure.

IL-10 protects monocytes and macrophages from complement-mediated lysis.

Phagocytes, such as monocytes and macrophages, are important cells of the innate immunity in the defense against microbes. So far, it is unclear how these cells survive at the site of combat against microbes, where a hostile inflammatory environment prevails with strong complement activity. We hypothesized that IL-10, a key cytokine involved in the resolution of inflammation, induces resistance to complement attack. Here, we demonstrate for the first time such a cell-protective effect of IL-10 on human monocytes and macrophages. IL-10 is indeed able to protect these cell types in an in vitro model of complement lysis triggered by an anti-MHCI antibody or by binding of zymosan. Investigating potential underlying mechanisms, we found that IL-10 up-regulated the expression of complement regulatory membrane protein CD59 and the general cell-protective stress protein HO-1 in human monocytes. However, further functional analysis failed to link these individual IL-10-mediated effects with the increased protection from complement lysis. Blocking the protective effect of CD59 with an antibody increased complement lysis but did not abrogate the IL-10-protective effect. Interestingly, chemical interference with HO-1 activity did abrogate the protective effect of IL-10, but siRNA-mediated knockdown of HO-1 did not confirm this observation. Our results suggest that IL-10 generates pathogen-clearing phagocytes, which are resistant to complement lysis and thereby, enabled to survive longer in a hostile inflammatory environment.