[The status of national and global hepatitis C elimination]. / Stand der nationalen und globalen Hepatitis-C-Elimination.

BACKGROUND: In 2016, the World Health Organization propagated the elimination of hepatitis C virus (HCV) by 2030 in order to address the public health threat posed by viral hepatitis. This article looks at the progress that has been made globally and in Germany since 2016. METHODS: A selective literature search was conducted, with particular focus on studies and reviews relating to the elimination of hepatitis C infection both globally and in Germany. RESULTS: In 2020, 56.8 million HCV infections were counted worldwide, which corresponds to a decline of 6.8 million since 2015. Countries that made a significant contribution to the elimination figures during this period included Egypt, Georgia, and Iceland, which were able to drastically reduce the number of HCV infections by means of national commitment in politics and healthcare. With regard to the status of elimination in Germany, the inclusion of screening for viral hepatitis in the general health check-up ("Check-up 35") in 2022/2023 has led to a significant increase in HCV case numbers. Globally and in Germany, men who have sex with men, intravenous drug users, migrants, and prison inmates are particularly vulnerable groups with regard to HCV infection. CONCLUSION: In order to sustainably eliminate HCV, it is necessary to optimize education and prevention strategies in risk groups. With regard to the subgroup of prison inmates, political measures must be used to create a standardized approach in prison medicine. At a global level, elimination in low- and middle-income countries needs to be promoted in the future.

Real-world effectiveness of voxilaprevir/velpatasvir/sofosbuvir in patients following DAA failure.

Background & Aims: Voxilaprevir/velpatasvir/sofosbuvir (VOX/VEL/SOF) is highly effective for re-treatment of direct-acting antiviral (DAA)-experienced patients with chronic HCV infection. In the present study, predictors of virologic treatment response were analyzed in an integrative analysis of three large real-world cohorts. Methods: Consecutive patients re-treated with VOX/VEL/SOF after DAA failure were enrolled between 2016 and 2021 in Austria, Belgium, Germany, Italy, Spain and Switzerland. Results: A total of 746 patients were included: median age was 56 (16-88) years and 77% were male. Most patients were infected with HCV genotype 1 (56%) and 3 (32%). 86% of patients carried resistance-associated substitutions in the NS3, NS5A or NS5B regions. Overall, 95.4% (683/716) of patients achieved a sustained virologic response. Treatment effectiveness was significantly affected by advanced liver disease (p <0.001), hepatocellular carcinoma (p <0.001), higher baseline ALT levels (p = 0.02), HCV genotype 3 (p <0.001), and prior VEL/SOF treatment (p = 0.01). In a multivariate analysis, only HCV genotype 3, hepatocellular carcinoma and cirrhosis turned out to be independent predictors of treatment failure. Resistance-associated substitutions, as well as the presence of rare genotypes, did not impact treatment outcome. The effectiveness of rescue therapy with glecaprevir/pibrentasvir and SOF, with or without ribavirin, for 12 to 24 weeks was found to be high (100%). Conclusions: Infection with HCV genotype 3, the presence of liver cancer and cirrhosis are independently associated with failure of VOX/VEL/SOF re-treatment. It is unclear whether the addition of ribavirin and/or extension of treatment duration may be effective to avoid virologic relapse on VOX/VEL/SOF. However, rescue treatment with glecaprevir/pibrentasvir+SOF seems to be effective. Impact and implications: Representative data on the effectiveness of voxilaprevir/velpatasvir/sofosbuvir (VOX/VEL/SOF) in clinical practice are still scarce and the collection of a larger number of patients with difficult-to-treat cofactors including the assessment of resistance-associated substitution profiles is required before more specific recommendations for optimal re-treatment in these patients can be given. Thus, we aimed to analyze treatment effectiveness and predictors of virologic response to VOX/VEL/SOF in an integrative analysis of three large real-word cohorts. The study results, derived from a multicenter cohort consisting of 746 patients, demonstrated that re-treatment with VOX/VEL/SOF is an effective salvage therapy associated with an overall per protocol sustained virologic response rate of 95%. Hepatocellular carcinoma onset, cirrhosis and HCV genotype 3 were identified as independent negative predictors of treatment response, whereas resistance-associated substitutions, as well as rare genotypes and chimera, did not impact sustained virologic response rates following re-treatment with VOX/VEL/SOF.

Correction: Is a higher frequency of esophageal dilations more effective in treating benign esophageal strictures? Retrospective, multicenter study.

[This corrects the article DOI: 10.1055/a-2117-8197.].

Is a higher frequency of esophageal dilations more effective in treating benign esophageal strictures? Retrospective, multicenter study.

Background and study aims There is still a lack of evidence-based recommendations concerning endoscopic bougienage in benign esophageal strictures. Our study aimed to assess the relevance of the time interval between endoscopic dilation (ED) sessions with regard to endoscopic and clinical response. Patients and methods We performed a retrospective study including patients treated with endoscopic bougienage for a benign esophageal stricture in two German centers. Primary endpoint was the number of ED until freedom from dysphagia was achieved. Secondary endpoints were analyses on reaching a diameter of 15 mm and on achieving clinical freedom from symptoms. Results Between April 2014 and March 2020, bougienage was used as the primary treatment for benign esophageal strictures in 238 patients (194 patients in Center 1; 44 patients in Center 2). Both centers differed in their endoscopic bougienage regime: Center 1 was characterized by a higher frequency of interventions compared to Center 2 (median: 2 days [range 1-28] vs. 10 days [range 1-41]; P <0.001). Clinical response was achieved significantly earlier using the high-frequency regimen in all patients except for those with post-radiogen strictures, who clinically benefited from a low-frequency ED program. Accordingly, patients receiving higher-frequency ED reached a significantly larger post-dilation diameter and considerably larger diameter differences. Conclusions The results of our study demonstrate that a treatment concept consisting of higher-frequency bougienages seems to be more effective in treating most types of esophageal stricture. Radiogenic strictures were the only types of stenoses that benefited from a lower frequency ED program.

Coinfections and antimicrobial treatment in a cohort of falciparum malaria in a non-endemic country: a 10-year experience.

INTRODUCTION: Falciparum malaria remains one of the deadliest infectious diseases worldwide. In Germany, it is mainly an imported infection among travellers. Rates of coinfection are often unknown, and a clinical rationale for the beneficial use of calculated antibiotic therapy in patients with malaria and suspected coinfection is lacking. METHODS: We conducted an analysis of all in-patients treated with falciparum malaria at a German infectious diseases centre in vicinity to one of Europe's major airports for 2010-2019. Logistic regression and time-to-event analysis were used to evaluate predictors for bacterial coinfection, the use of antibacterial substances, as well as their influence on clinical course. RESULTS: In total, 264 patients were included. Of those, 64% received an additional antibacterial therapy (n = 169). Twenty-nine patients (11.0%) were found to have suffered from a relevant bacterial coinfection, while only a small fraction had relevant bacteremia (n = 3, 1.4%). However, patients with severe malaria did not suffer from coinfections more frequently (p = 0.283). CRP levels were not a reliable predictor for a bacterial coinfection (OR 0.99, 95% CI 0.94-1.06, p = 0.850), while another clinical focus of infection was positively associated (OR 3.86, 95% CI 1.45-11.55, p = 0.010). CONCLUSION: Although bacterial coinfections were rare in patients with malaria at our centre, the risk does not seem negligible. These data point rather towards individual risk assessment in respective patients than to general empiric antibiotic use.

Primary Biliary Cholangitis (PBC)-Autoimmune Hepatitis (AIH) Variant Syndrome: Clinical Features, Response to Therapy and Long-Term Outcome.

INTRODUCTION: Standardization of diagnostic criteria of autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC) variant syndrome (AIH-PBC VS) has not been achieved so far and evidence-based recommendations for monitoring and treatment of the disease are still lacking. Our study aimed to assess the prevalence, biochemical, and serological features, as well as the clinical course, of VS. METHODS: We performed a retrospective study including all patients with VS between 1999 and 2020 in four German centers. Data on demographic parameters, biochemical and serological tests, treatment, and outcome were collected. RESULTS: Of 90 patients (3.1%) meeting Paris criteria for VS diagnosis, 65.6% showed AIH and PBC histological features, while biochemical Paris criteria were observed comparatively rarely. Further antibodies, which were not part of the diagnostic criteria of VS, were found in a subgroup of patients with available data (ACA: 30.0%; anti-CENP-A: 25.0%; anti-CENP-B: 33.3%; anti-SP100: 21.4%). Biochemical response was more frequently observed in patients treated with a combined therapy of ursodeoxycholic acid (UDCA) and immunosuppression (IS). Liver cirrhosis was detected in 31 patients (34.4%) and 25 patients (27.8%) developed clinical manifestations of portal hypertension. CONCLUSIONS: Biochemical Paris criteria of VS were rarely detected, thus implying that these cut-off values should be redefined. Regarding pharmacological treatment, combined therapy of UDCA and IS appeared to be more effective than monotherapy with UDCA.

Expanding epidemic of recently acquired HCV in HIV-coinfected patients over a period of 10 years.

Background & Aims: Ongoing transmission of HCV infections is associated with risk factors such as drug injection, needlestick injuries, and men who have sex with men (MSM). Ways of transmission, the course of acute infection, changes of virologic features, and incidence over time are not well known. Methods: Over a period of 10 years, n = 161 patients with recently acquired HCV infection (RAHC) (median follow-up 6.8 years) were prospectively enrolled. NS5B sequencing was performed to re-evaluate the HCV genotype (GT) and for phylogenetic analyses. Results: Patients with RAHC were mainly male (92.5%), MSM (90.1%), and HIV-coinfected (86.3%). Transmission risk factors for MSM and non-MSM were sexual risk behaviour (100 and 6.3%, respectively), injection drug use (9.7 and 37.5%, respectively), and nasal drug use (15.2 and 0%, respectively). Spontaneous and interferon- or direct-acting antiviral-based clearance rates were 13.6, 84.3 and 93.4%, respectively. Mean RAHC declined from 19.8 in the first to 13.2 in the past five study years. Although the majority of infections was caused by HCV GT1a, the frequency of HCV GT4d and slightly HCV GT3a increased over time. No relevant clustering of HCV isolates was observed in non-MSM. However, 45% of HCV GT1a and 100% of HCV GT4d MSM cases clustered with MSM isolates from other countries. Travel-associated infections were supported by personal data in an MSM subgroup. No international clustering was detected in MSM with HCV GT1b or HCV GT3a. Conclusions: RAHCs were mainly diagnosed in HIV-coinfected MSM patients and were associated with sexual risk behaviour. Spontaneous clearance rates were low, and phylogenetic clusters were observed in the majority of patients. Impact and Implications: We evaluated the occurrence and transmission of recently acquired HCV infections (RAHCs) over a period of 10 years. Our data demonstrate that the presence of RAHC was mainly found in HIV-coinfected MSM, with internationally connected transmission networks being observed in the majority of patients. Spontaneous clearance rates were low, and reinfection rates increased mainly driven by a small subset of MSM patients with high-risk behaviour.

Treatment of Non-Anastomotic Biliary Strictures after Liver Transplantation: How Effective Is Our Current Treatment Strategy?

BACKGROUND: Non-anastomotic biliary strictures (NAS) are a common cause of morbidity and mortality after liver transplantation. METHODS: All patients with NAS from 2008 to 2016 were retrospectively analyzed. The success rate and overall mortality of an ERCP-based stent program (EBSP) were the primary outcomes. RESULTS: A total of 40 (13.9%) patients with NAS were identified, of which 35 patients were further treated in an EBSP. Furthermore, 16 (46%) patients terminated EBSP successfully, and nine (26%) patients died during the program. All deaths were caused by cholangitis. Of those, one (11%) patient had an extrahepatic stricture, while the other eight patients had either intrahepatic (3, 33%) or combined extra- and intrahepatic strictures (5, 56%). Risk factors of overall mortality were age (p = 0.03), bilirubin (p < 0.0001), alanine transaminase (p = 0.006), and aspartate transaminase (p = 0.0003). The median duration of the stent program was 34 months (ITBL: 36 months; IBL: 10 months), and procedural complications were rare. CONCLUSIONS: EBSP is safe, but lengthy and successful in only about half the patients. Intrahepatic strictures were associated with an increased risk of cholangitis.

Is Olfactory Testing a Useful Diagnostic Tool to Identify SARS-CoV-2 Infections Early? A Cross-Sectional and Longitudinal Analysis.

BACKGROUND: Genesis and the prognostic value of olfactory dysfunction (OD) in COVID-19 remain partially described. The objective of our study was to characterize OD during SARS-CoV-2 infection and to examine whether testing of OD may be a useful tool in clinical practice in order to early identify patients with SARS-CoV-2 infection. METHODS: Olfactory function assessment was objectively carried out using the u-Smell-it® test. In a cross-sectional study part, we evaluated this test in a control cohort of SARS-CoV-2 negative tested patients, who attended the University Hospital Frankfurt between May 2021 and March 2022. In a second longitudinal study part, sensitivity and specificity of OD was evaluated as a diagnostic marker of a SARS-CoV-2 infection in Frankfurt am Main, Germany in SARS-CoV-2 infected patients and their close contacts. RESULTS: Among 494 SARS-CoV-2 negative tested patients, OD was detected in 45.7% and was found to be significantly associated with the male gender (p < 0.001), higher age (p < 0.001), cardiovascular and pulmonary comorbidities (p < 0.001; p = 0.03). Among 90 COVID-19 positive patients, OD was found in 65.6% and was significantly associated with male gender and positive smoking status (p = 0.04 each). Prevalence and severity of OD were significantly increased in infections with the Delta variant (B.1.617.2) compared to those with the Omicron variant (BA.1.1.529). Diagnostic sensitivity and specificity of OD for diagnosis of SARS-CoV-2 infection were 69% and 64%, respectively. CONCLUSION: OD is common in COVID-19 negative and positive tested patients with significantly different prevalence rates observed between different variants. Diagnostic accuracy of OD is not high enough to implement olfactory testing as a tool in diagnostic routine to early identify patients with a SARS-CoV-2 infection.

Risk Factors and Role of Antibiotic Prophylaxis for Wound Infections after Percutaneous Endoscopic Gastrostomy.

BACKGROUND AND STUDY AIM: The incidence of wound infections after percutaneous endoscopic gastrostomy (PEG) varies widely in recent studies. The present study systematically investigates the underlying risk factors for the development of wound infections in a large cohort of patients over a long-term follow-up period. PATIENTS AND METHODS: A retrospective cohort study of patients undergoing PEG insertion using either the pull or push technique was conducted and patients followed up for 3 years. Tube-related wound infections were identified, and pathogens regularly cultured from wound swabs. Adjusted analysis was performed via univariate and multivariate logistic regression analysis. RESULTS: 616 patients were included in this study. A total of 25% percent of patients developed wound infections upon PEG tube insertion and 6.5% showed recurrent infections. Nicotine abuse (p = 0.01), previous ischemic stroke (p = 0.01) and head and neck cancer (p < 0.001) showed an increased risk for wound infection after PEG placement. Moreover, radio-chemotherapy was associated with the occurrence of wound infections (p < 0.001). Infection rates were similar between pull and push cohorts. The most common bacterial pathogen detected was Enterobacterales (19.2%). Staphylococcus aureus, Pseudomonas aeruginosa and enterococci were frequently detected in recurrent infection (14.2%, 11.4% and 9.6%, respectively). Antibiotic prophylaxis showed no effect on infection rates. CONCLUSIONS: Wound infections after PEG placement are common and occasionally occur as recurrent infections. There is potential for improvement in everyday clinical practice, particularly regarding antibiotic prophylaxis in accordance with guidelines.

Clinical characteristics and outcome of Mycobacterium chimaera infections after cardiac surgery: systematic review and meta-analysis of 180 heater-cooler unit-associated cases.

OBJECTIVES: Since 2013, heater-cooler unit (HCU) associated Mycobacterium chimaera infections linked to a global outbreak have been described. These infections were characterised by high morbidity and mortality due to delayed diagnosis, as well as challenges in antimycobacterial and surgical therapy. This study aimed to investigate the clinical characteristics and outcome of published cases of HCU-associated M. chimaera infections. METHODS: We searched PubMed and the Web of Science until 15 June 2022 for case reports, case series, and cohort studies, without language restriction, on patients with M. chimaera infection and a prior history of cardiac surgery. In this systematic review of case reports, no risk of bias assessment could be performed. Clinical, microbiological, and radiological features were recorded. Logistic regression and time-to-event analyses were performed to identify the potential factors associated with better survival. RESULTS: One hundred eighty patients from 54 publications were included. Most patients underwent surgical aortic valve (67.0%; 118/176 of patients with available data) or combined aortic valve and root replacement (15.3%; 27/176). The median period between the time point of surgery and the first symptoms was 17 months (interquartile range 13-26 months). The overall case fatality rate was 45.5% (80/176), with a median survival of 24 months after the initiation of antimycobacterial therapy or diagnosis. A reoperation (including the removal or exchange of foreign material) was associated with better survival in multivariate logistic regression (OR 0.32 for lethal events; 95% CI 0.12-0.79; p 0.015) and in time-to-event analysis (p 0.0094). DISCUSSION: This systematic review and meta-analysis confirm the high overall mortality of HCU -associated disseminated M. chimaera infections after cardiac surgery. A reoperation seems to be associated with better survival. Physicians have to stay aware of this infection, as patients might still be present today due to the long latency period.

Pulmonary impairment independently determines mortality in critically ill patients with acute-on-chronic liver failure.

BACKGROUND & AIMS: In ACLF patients, an adequate risk stratification is essential, especially for liver transplant allocation, since ACLF is associated with high short-term mortality. The CLIF-C ACLF score is the best prognostic model to predict outcome in ACLF patients. While lung failure is generally regarded as signum malum in ICU care, this study aims to evaluate and quantify the role of pulmonary impairment on outcome in ACLF patients. METHODS: In this retrospective study, 498 patients with liver cirrhosis and admission to IMC/ICU were included. ACLF was defined according to EASL-CLIF criteria. Pulmonary impairment was classified into three groups: unimpaired ventilation, need for mechanical ventilation and defined pulmonary failure. These factors were analysed in different cohorts, including a propensity score-matched ACLF cohort. RESULTS: Mechanical ventilation and pulmonary failure were identified as independent risk factors for increased short-term mortality. In matched ACLF patients, the presence of pulmonary failure showed the highest 28-day mortality (83.7%), whereas mortality rates in ACLF with mechanical ventilation (67.3%) and ACLF without pulmonary impairment (38.8%) were considerably lower (p < .001). Especially in patients with pulmonary impairment, the CLIF-C ACLF score showed poor predictive accuracy. Adjusting the CLIF-C ACLF score for the grade of pulmonary impairment improved the prediction significantly. CONCLUSIONS: This study highlights that not only pulmonary failure but also mechanical ventilation is associated with worse prognosis in ACLF patients. The grade of pulmonary impairment should be considered in the risk assessment in ACLF patients. The new score may be useful in the selection of patients for liver transplantation.

Occurrence of extrapulmonary tuberculosis is associated with geographical origin: spatial characteristics of the Frankfurt TB cohort 2013-2018.

INTRODUCTION: Tuberculosis (TB) is caused by M. tuberculosis complex (MTB) and pulmonary tuberculosis (PTB) is its classical manifestation. However, in some regions of the world, extrapulmonary TB (EPTB) seems to be more frequent. METHODS: We performed a retrospective cohort study of all TB patients treated at University Hospital Frankfurt, Germany, for the time period 2013-2018. Patient charts were reviewed and demographic, clinical, and microbiological data recorded. Patients were subdivided according to their geographic origins. RESULTS: Of the 378 included patients, 309 were born outside Germany (81.7%). Three WHO regions were significantly associated with the occurrence of isolated EPTB: the South-East Asian Region (OR 3.37, CI 1.74-6.66, p < 0.001), the African Region (2.20, CI 1.25-3.90, p = 0.006), and the Eastern Mediterranean Region (OR 3.18, CI 1.78-5.76, p < 0.001). On a country level, seven countries of origin could be demonstrated to be significantly associated with the occurrence of isolated EPTB: India (OR 5.58, CI 2.30-14.20, p < 0.001), Nepal (OR 12.75, CI 1.73-259.28, p = 0.027), Afghanistan (OR 3.64, CI 1.14-11.98, p = 0.029), Pakistan (OR 3.64, CI 1.14-11.98, p = 0.029), Eritrea (OR 3.32, CI 1.52-7.47, p = 0.003), Somalia (OR 7.08, CI 2.77-19.43, p < 0.001), and Turkey (OR 9.56, CI 2.52-47.19, p = 0.002). CONCLUSION: Geographical origin is a predictor for the occurrence of extrapulmonary TB. This might be linked to a delay in diagnosis in these patients, as well as specific responsible impairments of the host's immune system, possible virulence factors of MTB, and relevant comorbidities.

Long-term persistence of HCV resistance-associated substitutions after DAA treatment failure.

BACKGROUND & AIMS: Data on the long-term persistence of HCV resistance-associated substitutions (RASs) after treatment with direct-acting antivirals (DAAs) are limited. This study evaluated the persistence of NS3, NS5A, and NS5B RASs for up to 5 years after the end of treatment (EOT). METHODS: We included samples from 678 individuals with an HCV genotype (GT) 1 or 3 infection and virologic DAA treatment failure collected in the European Resistance Database. NS3, NS5A, and NS5B were sequenced, and clinical parameters were evaluated. RESULTS: A total of 242 individuals with HCV GT1a (36%), 237 with GT1b (35%), and 199 (29%) with GT3 and a DAA failure were included. After protease inhibitor failure, the frequencies of NS3 RASs were 40-90% after the EOT. NS3 RASs disappeared rapidly in GT1b and GT3 after follow-up month 3 but were stable (≥60%) in GT1a owing to Q80K. The SOF-resistant NS5B RAS S282T was only found in individuals with GT3a. Non-nucleoside NS5B RASs were frequent in GT1 (56-80%) and decreased to 30% in GT1a but persisted in GT1b. NS5A RASs were very common in all GTs after NS5A inhibitor failure (88-95%), and even after follow-up month 24, their frequency was 65% and higher. However, RASs in GT1b had a stable course, whereas RASs in GT1a and GT3 declined slightly after follow-up month 24 (GT1a, 68%; GT1b, 95%; and GT3, 65%), mainly because of the slow decline of high-level resistant Y93H. CONCLUSIONS: We found that low-to medium-level RASs persisted, whereas high-level resistant RASs disappeared over time. Different patterns of RAS persistence according to HCV subtype could have implications for retreatment with first-generation DAAs and for global HCV elimination goals. IMPACT AND IMPLICATIONS: There are little data on the long-term persistence of HCV resistance-associated substitutions (RASs) after DAA treatment failure, and RASs could have an impact on the efficacy of a rescue treatment. Especially in countries with limited availability of VOX/VEL/SOF or G/P/SOF, different patterns of RAS persistence could have implications for retreatment with first-generation DAAs and for global HCV elimination goals. The different patterns of RAS persistence identified in this study can be used to derive general rules regarding the persistence of RASs after DAA failure that could be applied by physicians in less developed countries to plan individualized HCV retreatment.

Lung Opacity and Coronary Artery Calcium Score: A Combined Tool for Risk Stratification and Outcome Prediction in COVID-19 Patients.

PURPOSE: To assess and correlate pulmonary involvement and outcome of SARS-CoV-2 pneumonia with the degree of coronary plaque burden based on the CAC-DRS classification (Coronary Artery Calcium Data and Reporting System). METHODS: This retrospective study included 142 patients with confirmed SARS-CoV-2 pneumonia (58 ± 16 years; 57 women) who underwent non-contrast CT between January 2020 and August 2021 and were followed up for 129 ± 72 days. One experienced blinded radiologist analyzed CT series for the presence and extent of calcified plaque burden according to the visual and quantitative HU-based CAC-DRS Score. Pulmonary involvement was automatically evaluated with a dedicated software prototype by another two experienced radiologists and expressed as Opacity Score. RESULTS: CAC-DRS Scores derived from visual and quantitative image evaluation correlated well with the Opacity Score (r=0.81, 95% CI 0.76-0.86, and r=0.83, 95% CI 0.77-0.89, respectively; p<0.0001) with higher correlation in severe than in mild stage SARS-CoV-2 pneumonia (p<0.0001). Combined, CAC-DRS and Opacity Scores revealed great potential to discriminate fatal outcomes from a mild course of disease (AUC 0.938, 95% CI 0.89-0.97), and the need for intensive care treatment (AUC 0.801, 95% CI 0.77-0.83). Visual and quantitative CAC-DRS Scores provided independent prognostic information on all-cause mortality (p=0.0016 and p<0.0001, respectively), both in univariate and multivariate analysis. CONCLUSIONS: Coronary plaque burden is strongly correlated to pulmonary involvement, adverse outcome, and death due to respiratory failure in patients with SARS-CoV-2 pneumonia, offering great potential to identify individuals at high risk.

Diagnostic performance and predictive value of D-dimer testing in patients referred to the emergency department for suspected myocardial infarction.

PURPOSE: The study sought to assess the performance of D-dimer testing for the diagnosis of acute coronary syndrome (ACS) and prediction of outcomes in patients admitted for suspected myocardial infarction (MI). RESULTS: A total of 3,557 patients with suspected ACS presenting to a single center with a broad range of symptoms including atypical chest pain were retrospectively recruited between 02/2012-01/2019. Of the study cohort, 435 patients had unstable angina (UA), 420 non-ST-segment elevation myocardial infarction (NSTEMI), 22 ST-segment elevation myocardial infarction (STEMI), and 2,680 non-coronary chest pain. Plasma D-dimer concentrations in patients with hs-cTnT > 14 ng/L differed significantly from those with hs-cTnT < 14 ng/L (1.5 ± 3.6 mg/L vs. 0.5 ± 0.8 mg/L; p < 0.0001). Positive predictive value for a final diagnosis of ACS increased proportionally to rising D-dimer concentrations. The area under the curve (AUC) to discriminate STEMI from non-coronary chest pain (AUC 0.729, 95% confidence interval [CI] 0.71-0.75) was moderate and differed not significantly to UA (AUC 0.595, 95% CI 0.58-0.61; p = 0.0653). During a median follow-up of 29 months, higher D-dimer was associated with a significantly increased risk of recurrent MI (quartile 4 vs. 1: hazard ratio [HR], 6.9 [95% CI 1.2-39.9]; p < 0.0001) and higher all-cause mortality (HR, 17.4 [95% CI 4.3-69.9]; p < 0.0001). D-dimer was an independent predictor of all-cause mortality (p < 0.0001) and subsequent MI events (p = 0.0333). CONCLUSIONS: D-dimer testing revealed great potential to provide independent prognostic information on recurrent MI and all-cause mortality. However, D-dimers do not improve the diagnostic performance except if values exceed the 95th percentile.

High overall mortality of Mycobacterium genavense infections and impact of antimycobacterial therapy: Systematic review and individual patient data meta-analysis.

INTRODUCTION: Mycobacterium genavense is a fastidious slow growing mycobacterium (SGM) that causes disseminated infections in immunocompromised hosts. It has been described in HIV-positive individuals and increasingly in patients without HIV. The infections are difficult to treat and the optimal antimycobacterial regimen is still unknown. METHODS: An individual patient data meta-analysis was conducted aiming at including all hitherto published cases of infection with M. genavense. Clinical manifestations, microbiological data, dispositions and immunosuppression were recorded. Antimycobacterial therapies and mortality were analyzed by logistic regression and time-to-event analysis. RESULTS: We included 223 patients with infection due to M. genavense published from 1992 to 2021. While the majority was HIV positive (n = 171, 76.7%), 52 patients were non-HIV-patients (23.3%), 36 of whom received immunosuppressive therapy (69%). We could confirm the bacterium's tropism for the gastrointestinal tract with abdominal pain, hepato-/splenomegaly and abdominal lymphadenopathy being major clinical manifestations. More than 90% of patients received antimycobacterial therapy. The regimens consisted mainly of macrolides, rifamycins and ethambutol. Overall mortality was high, but in logistic regression and time-to-event analysis a macrolide containing regimen was associated with better outcomes. CONCLUSION: In this first individual patient data meta-analysis of infections with M. genavense we confirm its tropism for the gastrointestinal tract. The high overall mortality underlines the clinical relevance of infection with this bacterium for the individual patient. In addition, our data give a hint that a macrolide containing regimen is associated with better survival.

Hepatic sarcoidosis: Clinical characteristics and outcome.

BACKGROUND & AIMS: Clinical manifestation of hepatic involvement in sarcoidosis can vary from asymptomatic disease to severe complications such as cirrhosis and portal hypertension. However, data on hepatic sarcoidosis are limited, and evidence-based recommendations are lacking. Our study aimed to assess the features and clinical course of hepatic sarcoidosis in a predominantly Caucasian cohort. METHODS: We performed a retrospective study including all patients with hepatic sarcoidosis between 2004 and 2020 in 5 German centres. The median follow-up time was 36 months (range 0.0-195). Data on demographic parameters, clinical manifestations, diagnostic test results, treatment, and outcome were collected. RESULTS: A total of 1,476 patients with sarcoidosis and 62 patients with hepatic involvement (4.2%) were identified. Of the patients, 51.6% were female, and 80.6% were Caucasian. Most patients were asymptomatic and were observed to have a cholestatic pattern of liver enzyme elevations. Cirrhosis was detected in 9 patients (14.5%), of whom 6 developed clinical manifestations of portal hypertension. Fifty-four patients were medically treated, most commonly with glucocorticoids (69.4%) or ursodeoxycholic acid (UDCA) (40.3%). Levels of alkaline phosphatase (ALP) decreased by 60.8% on average from baseline in patients treated with glucocorticoids and by 59.9% in patients treated with UDCA. Seventeen patients received treatment augmentation with a second line agent, of whom 8 patients normalised ALP levels during follow-up. None of the patients underwent liver transplantation or developed hepatocellular carcinoma (HCC). Three of the patients died during follow-up owing to liver-related complications. CONCLUSIONS: Hepatic involvement in sarcoidosis was found in 4.2% of patients with sarcoidosis and was clinically significant in 14.5% of those. These findings highlight the importance of early identifying, monitoring, and treating hepatic sarcoidosis, given its increased mortality when associated with end-stage liver disease. LAY SUMMARY: Clinical diagnostic and surveillance of hepatic involvement in sarcoidosis has not been standardised, and management of hepatic involvement is a clinical challenge, since it remains poorly characterised in many ways. Our results show that one-third of patients with hepatic sarcoidosis presented with clinically significant portal hypertension, 14.5% suffered from cirrhosis, and 3 patients died owing to liver-related complications. Regarding pharmacological treatment options, corticosteroids and UDCA were the medical agents most frequently used, and both of them have been shown to induce biochemical response in the majority of patients. These findings highlight the importance of correctly and early identifying hepatic involvement in sarcoidosis, because of the potentially progressive course of disease.

Disseminated disease due to non-tuberculous mycobacteria in HIV positive patients: A retrospective case control study.

INTRODUCTION: Disseminated infection due to non-tuberculous mycobacteria has been a major factor of mortality and comorbidity in HIV patients. Until 2018, U.S. American guidelines have recommended antimycobacterial prophylaxis in patients with low CD4 cell counts, a practice that has not been adopted in Europe. This study aimed at examining the impact of disseminated NTM disease on clinical outcome in German HIV patients with a severe immunodeficiency. MATERIALS AND METHODS: In this retrospective case control study, HIV patients with disseminated NTM disease were identified by retrospective chart review and matched by their CD4 cell counts to HIV patients without NTM infection in a 1:1 alocation. Primary endpoints were mortality and time to first rehospitalisation. In addition, other opportunistic diseases, as well as antimycobacterial and antiretroviral treatments were examined. RESULTS: Between 2006 and 2016, we identified 37 HIV patients with disseminated NTM disease. Most of them were suffering from infections due to M. avium complex (n = 31, 77.5%). Time to event analysis showed a non-significant trend to higher mortality in patients with disseminated NTM disease (p = 0.24). Rehospitalisation took place significantly earlier in patients with disseminated NTM infections (median 40.5 days vs. 109 days, p<0.0001). CONCLUSION: In this retrospective case control study, we could demonstrate that mortality is not significantly higher in HIV patients with disseminated NTM disease in the ART era, but that they require specialised medical attention in the first months following discharge.

Point Shear-Wave Elastography Using Acoustic Radiation Force Impulse Imaging for the Prediction of Liver-Related Events in Patients With Chronic Viral Hepatitis.

Chronic viral hepatitis is associated with substantial morbidity and mortality worldwide. The aim of our study was to assess the ability of point shear-wave elastography (pSWE) using acoustic radiation force impulse imaging for the prediction of the following liver-related events (LREs): new diagnosis of HCC, liver transplantation, or liver-related death (hepatic decompensation was not included as an LRE). pSWE was performed at study inclusion and compared with liver histology, transient elastography (TE), and serologic biomarkers (aspartate aminotransferase to platelet ratio index, Fibrosis-4, FibroTest). The performance of pSWE and TE to predict LREs was assessed by calculating the area under the receiver operating characteristic curve and a Cox proportional-hazards regression model. A total of 254 patients with a median follow-up of 78 months were included in the study. LRE occurred in 28 patients (11%) during follow-up. In both patients with hepatitis B virus and hepatitis C virus (HCV), pSWE showed significant correlations with noninvasive tests and TE, and median pSWE and TE values were significantly different between patients with LREs and patients without LREs (both P < 0.0001). In patients with HCV, the area under the receiver operating characteristic curve for pSWE and TE to predict LREs were comparable: 0.859 (95% confidence interval [CI], 0.747-0.969) and 0.852 (95% CI, 0.737-0.967) (P = 0.93). In Cox regression analysis, pSWE independently predicted LREs in all patients with HCV (hazard ratio, 17.9; 95% CI, 5.21-61-17; P < 0.0001) and those who later received direct-acting antiviral therapy (hazard ratio, 17.11; 95% CI, 3.88-75.55; P = 0.0002). Conclusion: Our study shows good comparability between pSWE and TE. pSWE is a promising tool for the prediction of LREs in patients with viral hepatitis, particularly those with chronic HCV. Further studies are needed to confirm our data and assess their prognostic value in other liver diseases.