Patterns, predictors and prognostic relevance of high-grade hematotoxicity after temozolomide or temozolomide-lomustine in the CeTeG/NOA-09 trial.

PURPOSE: In the randomized phase III trial CeTeG/NOA-09, temozolomide (TMZ)/lomustine (CCNU) combination therapy was superior to TMZ in newly diagnosed MGMT methylated glioblastoma, albeit reporting more frequent hematotoxicity. Here, we analyze high grade hematotoxicity and its prognostic relevance in the trial population. METHODS: Descriptive and comparative analysis of hematotoxicity adverse events ≥ grade 3 (HAE) according to the Common Terminology of Clinical Adverse Events, version 4.0 was performed. The association of HAE with survival was assessed in a landmark analysis. Logistic regression analysis was performed to predict HAE during the concomitant phase of chemotherapy. RESULTS: HAE occurred in 36.4% and 28.6% of patients under CCNU/TMZ and TMZ treatment, respectively. The median onset of the first HAE was during concomitant chemotherapy (i.e. first CCNU/TMZ course or daily TMZ therapy), and 42.9% of patients with HAE receiving further courses experienced repeat HAE. Median HAE duration was similar between treatment arms (CCNU/TMZ 11.5; TMZ 13 days). Chemotherapy was more often discontinued due to HAE in CCNU/TMZ than in TMZ (19.7 vs. 6.3%, p = 0.036). The occurrence of HAE was not associated with survival differences (p = 0.76). Regression analysis confirmed older age (OR 1.08) and female sex (OR 2.47), but not treatment arm, as predictors of HAE. CONCLUSION: Older age and female sex are associated with higher incidence of HAE. Although occurrence of HAE was not associated with shorter survival, reliable prediction of patients at risk might be beneficial to allow optimal management of therapy and allocation of supportive measures. TRIAL REGISTRATION: NCT01149109.

Influence of dietary supplementation of short-chain fatty acid sodium propionate in people living with HIV (PLHIV).

BACKGROUND: Non-AIDS-associated chronic diseases in HIV+ patients have been on the rise since the advent of antiretroviral therapy. Especially cardiovascular diseases and disruption in the gastrointestinal tract have limited health-related quality of life (QoL). Several of those complications have been associated with chronic systemic inflammation. Short-chain fatty acids (SCFA), with propionate as one of the major compounds, have been described as an important link between gut microbiota and the immune system, defining the pro- and the anti-inflammatory milieu through direct and indirect regulation of T-cell homeostasis. The effects of dietary supplementation of sodium propionate (SP) in people living with HIV (PLHIV) have not yet been investigated prior to this study. OBJECTIVES: To investigate the impact of SP uptake among PLHIV and its relevance to improve QoL, the study aimed to investigate metabolic, immunological, microbiome and patient-reported QoL-related changes post-SP supplementation with follow-up. METHODS: A prospective, non-randomized, controlled, monocentric interventional study was conducted in WIR, Center for Sexual Health and Medicine, in Bochum, Germany. 32 HIV+ patients with unaltered ART-regimen in the last three months were included. Participants were given SP for a duration of 12 weeks in the form of daily oral supplementation and were additionally followed-up for another 12 weeks. RESULTS: The supplementation of SP was well tolerated. We found an improvement in lipid profiles and long-term blood glucose levels. A decrease in pro-inflammatory cytokines and a depletion of effector T cells was observed. Regulatory T cells and IL-10 decreased. Furthermore, changes in taxonomic composition of the microbiome during follow-up were observed and improvement of items of self-reported life-quality assessment. CONCLUSION: Taken together, the beneficial impact of SP in PLHIV reflects its potential in improving metabolic parameters and modulating pro-inflammatory immune responses. Thus, possibly reducing the risk of cardiovascular disorders and facilitating long-term improvement of the gut flora.

Prediction of future cardiovascular events by Framingham, SCORE and asCVD risk scores is less accurate in HIV-positive individuals from the HIV-HEART Study compared with the general population.

OBJECTIVES: Cardiovascular diseases (CVDs) occur more often in people living with HIV (PLWH) than in the general population. It has been reported that CVD risk scores developed for the general population underestimate the CVD risk in PLWH. Performances of the Framingham Risk Score (FRS), the Systematic Coronary Risk Evaluation (SCORE) and the atherosclerotic cardiovascular disease (asCVD) risk score in PLWH were compared with the general population to quantify score-specific differences in risk prediction. METHODS: HIV-positive outpatients from the HIV-HEART (HIVH) study (n = 567) were compared with participants from the population-based Heinz Nixdorf Recall (HNR) study (n ~ 4440) both recruited from the German Ruhr area. During a follow-up time of around 5 years, the associations between the FRS and incident CVD and peripheral artery disease (CVD_pAD), SCORE and coronary heart disease (CHD), and asCVD and incident CVD were examined using logistic regression. Score performances were assessed by comparing the areas under the curve (AUCs). RESULTS: The mean ages were 52.9 ± 6.7 and 59.1 ± 7.7 years in the HIVH and HNR studies, respectively. There were fewer incident CVD events in the HNR study than in the HIVH study (CVD_pAD: 3.9% vs. 12.1%; CHD: 2.1% vs. 7.8%; CVD: 3.5% vs. 9.9%). Age- and sex-adjusted CVD risk was greater with increasing FRS, SCORE and asCVD in both cohorts, but the scores performed more accurately in the HNR than in HIVH study (AUCs FRS: 0.71 vs. 0.65; SCORE: 0.70 vs. 0.62; asCVD: 0.74 vs. 0.62). CONCLUSIONS: Associations between risk scores and future CVD were observed in both cohorts, but the score performances were less reliable in PLWH than in the general population.

Sexual behaviour, STI knowledge and Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) prevalence in an asymptomatic cohort in Ruhr-area, Germany: PreYoungGo study.

BACKGROUND AND OBJECTIVES: STIs present a significant threat to individual and public health, disproportionately affecting youth. The study aimed to evaluate (a) the prevalence of asymptomatic Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections among youth using a rapid assay platform, (b) the participants' sexual behaviour and STI knowledge, (c) the utility of the rapid assay in reducing diagnosis-to-treatment time. METHODS: In this study, 272 subjects (14-31 years) were included between 12/2016 and 7/2018. A questionnaire was used to collect sociodemographic data, sexual behaviour and STI knowledge. Prevalence of CT and NG infections were tested from oral, vaginal and anal swabs for women and oral, anal swabs and urine for men, using the Cepheid Xpert® CT/NG assay. Time intervals between (i) test to the time the patient were informed of the result (turn around time - TAT) and (ii) test to therapy initiation was documented. RESULTS: Of the 272 subjects (48.9% female, 48.9% male, undisclosed 2.2%), 56.6 % reported university education. 46.6% were men who have sex with men (MSM), and 47.4% of women and 63.1% of men had anal intercourse. 59.9% had previously been tested for HIV, while only 39.7% had for CT, 20.6% for NG. Among these asymptomatic youth 7.7% were positive for CT and 5.5% for NG. The localization of CT were 3.7% genital, 5.5% anal and 2.2% oral, while the corresponding localization of NG were 0.4%, 2.9%, 4.4% respectively. 91.8% of the participants were informed of a positive result within 24 h with a median TAT of 03:09 h. 73.3% initiated therapy within 24 h, with a median time from testing to therapy initiation being 06:50 h. CONCLUSION: Asypmtomatic CT and NG infections are common and often not tested in persons at risk. The Cepheid Xpert® CT/NG assay is an effective strategy as it reduces STI diagnosis-to-treatment time to less than a day.

[Sonographic diagnostics of liver tumors]. / Sonographische Diagnostik bei Lebertumoren.

Liver tumors are often incidentally found during ultrasound examinations. The decision on further diagnostic imaging depends on the clinical context and the appearance in B mode ultrasound. This review highlights the role of grey scale and contrast-enhanced ultrasound (CEUS) and summarizes the ultrasonographic key features of the most common benign and malignant liver tumors. Conventional grey scale ultrasound is recommended in several guidelines for screening and follow-up of liver tumors in certain risk populations but its ability to characterize liver tumors is limited in most cases. The CEUS has an excellent tolerability and enables liver tumor characterization with a high sensitivity and specificity. The diagnostic value of CEUS is comparable to magnetic resonance imaging. In the case of unclear lesions, inconclusive findings by different imaging methods or if molecular targeted treatment is pursued, ultrasound-guided biopsy is often mandatory. Ultrasound is a rapidly and ubiquitously available method for the detection of liver tumors and CEUS is the only imaging method that enables real-time examination of all contrast phases in the liver. It should therefore be used as the first line imaging method for liver tumor characterization.

[Management of benign liver tumors]. / Management benigner Lebertumoren.

Benign liver tumors form a heterogeneous group. The most frequent forms include simple cysts, hemangiomas, focal nodular hyperplasia and hepatocellular adenomas. They are often incidentally detected during routine sonography. The diagnosis of a liver tumor not uncommonly causes anxiety and insecurity in those affected, which is why a rapid and reliable diagnostic procedure should be carried out. Because some tumors, particularly hepatocellular adenomas, are of prognostic relevance due to the potential risk of malignant transformation, a correct classification should always be strived for. The type and extent of diagnostic clarification depend on the clinical and patient-related risk factors. This article describes the most important benign space-occupying lesions. The etiology, clinical manifestations and diagnostics as well as possible necessary treatment measures are presented.

[Diseases and diagnosis of the biliary system : When does the gastroenterologist need the radiologist?] / Erkrankungen und Diagnostik der Gallenwege : Wann braucht der Gastroenterologe den Radiologen?

CLINICAL ISSUE: Biliary diseases require fast and rational use of diagnostic tests by both gastroenterologists and radiologists. STANDARD TREATMENT: Standard diagnostic workup includes transabdominal ultrasound, endoscopic retrograde cholangiography (ERC), endoscopic ultrasound, direct cholangioscopy, magnetic resonance cholangiopancreatography (MRI/MRCP), and computed tomography (CT). TREATMENT INNOVATIONS: Modular cholangioscopy is a novel diagnostic method. DIAGNOSTIC WORK-UP: The goal of diagnostic examinations is the determination of the location of obstructions and differentiation of benign from malignant lesions. ACHIEVEMENTS: Transabdominal ultrasound is risk-free and can show the gallbladder in great detail providing high diagnostic accuracy in most conditions. Endoscopic ultrasound, ERC and/or cholangioscopy are powerful tools to investigate the large bile ducts but are associated with inherent procedural risks. PRACTICAL RECOMMENDATIONS: Gall bladder diseases can often be diagnosed with transabdominal ultrasound alone. Bile duct disease often requires the use of endoscopic ultrasound, ERC and/or cholangioscopy.

[Profile of Kaposi sarcoma patients in the competence network HIV/AIDS]. / Profil der Kaposi-Sarkom-Patienten im Kompetenznetz HIV/AIDS.

BACKGROUND: Kaposi's sarcoma (KS) represents the most common AIDS-defining neoplasm. Only very few studies regarding the course and treatment of human immunodeficiency virus (HIV)-associated KS have been carried out in Germany. OBJECTIVE: In this study the course of HIV-associated KS was observed in patients from the cohort database of the competence network for HIV/AIDS. MATERIAL AND METHODS: Data from HIV-associated KS patients from 9 German core centers from 1987 to 2011 were retrospectively collected. Kaplan-Meier curves for the recurrence and survival probability were calculated. RESULTS: In 222 patients KS was diagnosed at a median age of 38.5 ± 10.1 years. Men were almost exclusively affected (97.7%). The HIV viral load at the time of diagnosis was in 7.4% <50 copies/ml. Of the patients 55.5% developed KS with a CD4 cell count of <200 cells/µl and 9.5% with >500 cells/µl. In 68 patients KS therapy consisted exclusively of the optimization or initiation of antiretroviral therapy (ART). In addition, 71 patients were treated with pegylated liposomal doxorubicin. During the median follow-up period of 8.9 ± 4.9 years, 80.2% of the patients were free of KS recurrence. Survival rates after 5 and 10 years were 96.8% and 91.3%, respectively. CONCLUSION: Even with a good immune status HIV-associated KS occurred. An effective ART was the most important mainstay of therapy. With appropriate therapy, HIV-positive patients with KS showed a good survival rate.

Asymptomatic anal sexually transmitted infections in HIV-positive men attending anal cancer screening.

BACKGROUND: HIV-positive men who have sex with men (HIV+MSM) have an increased risk for anal dysplasia and for sexually transmitted infections (STIs). OBJECTIVES: We determined the positivity rates of Chlamydia trachomatis (CT), Neisseria gonorrhoea (NG), Mycoplasma genitalium (MG) and syphilis in HIV+MSM participating in an anal cancer screening programme. METHODS: In total, 852 intra-anal swabs were collected from 503 HIV+MSM between 2012 and 2014. Anal cytology and polymerase chain reaction assays for human papillomavirus (HPV), CT, NG and MG detection were performed. The syphilis status was determined serologically. Risk factors for STIs were explored by multiple logistic regression analysis. RESULTS: In total 20·7% (104 of 503) of the patients had an STI other than HPV within the study period. The most common was CT, found in 10·9%, followed by NG (8·9%) and MG (4·2%). Early syphilis was detected in 4·6% and past syphilis in 44·5% of the HIV+MSM. Eighteen patients (3·6%) had more than one STI episode, and 90·6% of the 127 cases of STIs were asymptomatic. Age, anal HPV infection, abnormal anal cytology and previous syphilis were risk factors for STI. CONCLUSIONS: Anal STIs are frequent and mostly asymptomatic in HIV+MSM participating in anal cancer screening. STI screening should be incorporated into anal cancer screening programmes for HIV+MSM.

Viral load strategy: impact on risk behaviour and serocommunication of men who have sex with men in specialized care.

BACKGROUND: Incidence and prevalence of HIV are continuously high in German men, who have sex with men (MSM). Different transmission risk minimizing strategies have been observed. The viral load strategy rates patients unlikely to be sexually infectious if their viral load under effective therapy is stably suppressed during 6 months and no other sexually transmitted infections are present. OBJECTIVES: We aim to objectify the current popularity of the viral load strategy, the adherence to basic conditions and its impact on risk behaviour and serocommunication. Until now, no data on a German sample of HIV-positive MSM in regular specialized outpatient care are available. METHODS: Cross-sectional study with group comparisons between user group and non-user-group of the viral load strategy. Self-report questionnaires were conducted with 269 sexually active German HIV+MSM under effective treatment in specialized outpatient care. Structured interviews gathered additional information about approach to and realization of definite action levels concerning sexual risk behaviour and transmission risk minimizing strategies. RESULTS: Twenty-seven of 269 participants (10%) affirmed knowledge of having an undetectable viral load and stated this to be criteria for unprotected sexual behaviour. This subgroup reported more unprotected insertive (P = 0.018) and receptive anal intercourse (P = 0.042), more anonymous sex partners (P = 0.008) and less consistent safer sex. Analysing serocommunication, less addressing HIV/AIDS in general (P = 0.043) and less disclosing to sex partners (P = 0.023) was found, especially in anonymous settings. Differentiating serocommunication characteristics, a focus on seroguessing was depicted. CONCLUSIONS: The user group of the viral load strategy is small. But a less frequent, more reactive and assumptive serocommunication leads to an imprecise information exchange paired with higher frequency of risky behaviour, especially in anonymous settings, where frank serocommunication is often avoided. The targeted group of the viral load strategy diverges greatly from the user group.

The male ScreenING Study: prevalence of HPV-related genital and anal lesions in an urban cohort of HIV-positive men in Germany.

BACKGROUND: Human papillomaviruses (HPV) induce condylomata, anogenital cancers and their precursor lesions as anal or penile intraepithelial neoplasia (AIN/PIN). HIV-positive individuals have an increased risk for the development of anogenital HPV-induced lesions. OBJECTIVE: Estimation of the prevalence of HPV-related anogenital benign and malignant lesions in HIV-infected men attending a screening programme. METHODS: Four hundred HIV-positive men [98% men who have sex with men (MSM)] were enrolled in this prospective study from 2008 to 2011. All patients received an inspection of the anogenital region, digital rectal examination, high-resolution anoscopy (HRA), anal cytology, anal/penile histology if required, and HPV-typing of anal and penile swabs. RESULTS: At baseline, 75% (n = 302) of the men had abnormal anal cytological/histological results. 41% presented with low-grade (n = 164), 24% with high-grade anal dysplasia (n = 95) and two men with invasive anal cancer. 2.3% had PIN (n = 9) and one patient had penile cancer at baseline. Throughout the study period, 75% had anal dysplasia (low-grade n = 177, high-grade n = 125), 3.3% (n = 13) had PIN and two further patients developed anal cancer. Within the study period, 52.8% (n = 211) had condylomata (49% anal, 15% penile, 11% anal plus penile condylomata). At baseline, 88.5% of anal and 39.3% of penile swabs were HPV-DNA positive, and 77.8% of anal and 26.5% of penile swabs carried high-risk HPV-types. HPV16 was the most frequent HPV-type. CONCLUSION: HIV-positive MSM have a high risk for HPV-induced condylomata, (pre)malignant anogenital lesions and anogenital cancers. Screening for HPV-induced dysplasia is crucial to avoid progression to invasive carcinomas. Additionally, HPV-vaccination recommendations should be extended to high-risk populations.

Percutaneous sclerotherapy of liver and renal cysts, comments on the EFSUMB guidelines.

Cystic lesions in the liver and kidneys are common incidental findings. They are generally benign and require no treatment. They can appear sporadically or as part of a syndrome, and are characterised by their anechoic structure and posterior enhancement in ultrasound imaging. Increased size, haemorrhage or infection of a cyst can lead to development of symptoms. Along with surgical options and laparoscopic cyst fenestration, ultrasound-guided sclerotherapy of symptomatic cysts represents an effective and safe minimally invasive treatment option.

Evaluation of Liver and Spleen Stiffness with Acoustic Radiation Force Impulse Quantification Elastography for Diagnosing Clinically Significant Portal Hypertension.

PURPOSE: Hepatic vein pressure gradient (HVPG) is the gold standard for diagnosing clinically significant portal hypertension (CSPH). The aim of this study was to investigate-in comparison to HVPG-the ability to diagnose CSPH by liver and spleen stiffness measurements obtained by acoustic radiation force impulse (ARFI) imaging. MATERIALS AND METHODS: A total of 78 patients (mean age: 53 ±â€Š13 years, 62 % male) with chronic liver disease were enrolled in this study. Each patient received liver (LSM) and spleen (SSM) stiffness measurements by ARFI, an HVPG measurement and a transjugular liver biopsy on the same day. Patients were classified according to their HVPG into three different groups: HVPG < 10 mmHg, HVPG ≥ 10-< 12 mmHg and HVPG ≥ 12 mmHg. RESULTS: LSM, SSM were significantly higher in patients with HVPG ≥ 10 - < 12 in comparison to HVPG < 10 mmHg (p < 0.001 and p < 0.001, respectively), and in patients with HVPG ≥ 12 mmHg in comparison to ≥ 10 - < 12 mmHg (p < 0.001 and p < 0.001, respectively). LSM and SSM were able to diagnose HVPG ≥ 10 mmHg and HVPG ≥ 12 mmHg with high diagnostic performance (AUC LSM: 0.93 and 0.87, respectively; AUC SSM: 0.97 and 0.95, respectively). The AUC of SSM in predicting esophageal varices (EVs) plus HVPG ≥ 10 mmHg and EVs plus HVPG ≥ 12 mmHg were higher compared to LSM in both groups of patients (SSM: 0.90 and 0.93 vs. LSM: 0.84 and 0.88, respectively). No significant difference between both AUCs was detected in the different HVPG groups. In the multivariate -analysis SSM remained a factor predicting HVPG (HVPG > 10 mmHg p = 0.007; HVPG ≥ 12 mmHg p = 0.003). CONCLUSION: LSM and SSM by ARFI are noninvasive diagnostic tools that may help in diagnosing CSPH. LSM and SSM could be used as a guiding noninvasive screening tool in patients with esophageal varices requiring endoscopic evaluation.

Therapy and prophylaxis of opportunistic infections in HIV-infected patients: a guideline by the German and Austrian AIDS societies (DAIG/ÖAG) (AWMF 055/066).

INTRODUCTION: There was a growing need for practical guidelines for the most common OIs in Germany and Austria under consideration of the local epidemiological conditions. MATERIALS AND METHODS: The German and Austrian AIDS societies developed these guidelines between March 2010 and November 2011. A structured Medline research was performed for 12 diseases, namely Immune reconstitution inflammatory syndrome, Pneumocystis jiroveci pneumonia, cerebral toxoplasmosis, cytomegalovirus manifestations, candidiasis, herpes simplex virus infections, varizella zoster virus infections, progressive multifocal leucencephalopathy, cryptosporidiosis, cryptococcosis, nontuberculosis mycobacteria infections and tuberculosis. Due to the lack of evidence by randomized controlled trials, part of the guidelines reflects expert opinions. The German version was accepted by the German and Austrian AIDS Societies and was previously published by the Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF; German Association of the Scientific Medical Societies). CONCLUSION: The review presented here is a translation of a short version of the German-Austrian Guidelines of opportunistic infections in HIV patients. These guidelines are well-accepted in a clinical setting in both Germany and Austria. They lead to a similar treatment of a heterogeneous group of patients in these countries.

Substance use and sexual risk behaviour among HIV-positive men who have sex with men in specialized out-patient clinics.

OBJECTIVES: Unprotected sexual intercourse between men who have sex with men (MSM) is the most common route of HIV infection in Germany. Approximately 70% of newly infected people are MSM. Substance use is a determinant of sexual risk behaviour in the general population, but also in the MSM subpopulation. There are only a few studies, from the USA, on the correlation between substance use and sexual risk behaviour in HIV-infected MSM in specialized care. METHODS: In a German sample of 445 HIV-infected MSM treated in specialized out-patient clinics, the influence of substance use on sexual risk behaviour was investigated. Information was obtained from subjects using self-report questionnaires and a structured interview. RESULTS: Recreational drug use was common. The prevalences of cannabis addiction (4.5%), harmful use of cannabis (4.3%) and harmful use of dissociative anaesthetics (0.4%) were higher than in the general German male population. A substantial proportion of patients reported unprotected insertive (32.9%) and receptive (34.6%) anal intercourse during the last 12 months. Use of cannabis, amyl nitrite, dissociative anaesthetics, cocaine, amphetamines and erectile dysfunction medication was significantly correlated with unprotected sexual contacts. Substance use in the context of sexual activity significantly increased sexual risk behaviour. CONCLUSIONS: Substance use, especially in the context of sexual activity, should be taken into account when developing new prevention and intervention programmes aimed at reducing sexual risk behaviour in HIV-infected MSM currently in specialized care.

Gender differences in patient receiving liver transplantation for viral hepatitis.

INTRODUCTION: The course of viral hepatitis shows wide interindividual differences, ranging from asymptomatic disease to liver failure. Only limited data on gender differences in patients undergoing liver transplantation (OLT) exist. We studied the gender distribution in patients who underwent liver transplantation for viral hepatitis. METHODS: A retrospective analysis was performed on a cohort of 368 patients who underwent OLT for viral hepatitis-associated acute or chronic liver failure. In 96 of them, additional hepatocellular carcinoma (HCC) was present at transplantation. Gender ratios of the different hepatitis virus infections and in relation to HCC were evaluated. RESULTS: Significantly more males than females underwent OLT for chronic HBV. In contrast, patients after OLT for fulminant HBV were more frequently females. In patients transplanted for chronic HCV or HDV, no significant gender differences were found. However, men presented more frequently with HCC in both groups of chronic liver disease. CONCLUSIONS: There was a gender difference in HBV infection with more women developing fulminant hepatic failure in acute HBV while more men progressed to end-stage liver disease in chronic HBV. The role of gender in chronic HCV and HDV infection was less pronounced, except for a male predominance among patients with HCC.

[HIV infection]. / HIV-Infektion.

The skin can be an indicator of decreased immunocompetence. Dermatological markers include new and extensive seborrheic eczema, psoriasis without a family history, widespread herpes zoster in young adults, oral hairy leucoplakia and mollusca in adults. In these cases an HIV test should be offered. During the last 15 years the clinical picture of HIV has changed dramatically. Almost every year new drugs with better efficacy, lower pill burden and less side effects have been approved. Life expectancy is close to normal in western countries. In spite of better treatment options, prevention is the key to stop the worldwide epidemic. Awareness campaigns have to account for the synergies between HIV and other sexually transmitted diseases. This poses a great challenge for dermatovenereology.