The burden in chronic prurigo: patients with chronic prurigo suffer more than patients with chronic pruritus on non-lesional skin: A comparative, retrospective, explorative statistical analysis of 4,484 patients in a real-world cohort.

BACKGROUND: Chronic prurigo (CPG) is known as a high burdensome disease characterized by severe pruritus and multiple pruriginous lesions. Interestingly, the disease-specific burden is not well established and there are no data which compare the impact of CPG with chronic pruritus (CP) on non-lesional skin (CP-NL). OBJECTIVES: To address this issue, we analysed datasets from 4484 patients with either CPG or CP-NL. METHODS: Demographic medical data and additional information collected by validated patient reported outcome tools were analysed. The visual analogue scale and numerical rating scale (NRS) were used for assessing the pruritus intensity, the ItchyQoL for patients' quality of life, the Hospital Anxiety and Depression Scale and the Patient Needs Questionnaire' as a part of Patient Benefit Index for Pruritus for measuring the importance of 27 patient needs in terms of treatment goals. The Neuroderm questionnaire was used to assess the history of pruritus characteristics and the impact on sleep. RESULTS: Patients with CPG suffered longer and with a higher intensity from pruritus [NRS worst the last 24 h, CPG 6.0 (4.0;8.0) vs. CP-NL 3.0 (5.0;7.0), P < 0.001]. In them, pruritus occurred more often and the whole day and night which led to more loss in sleeping hours [CPG 3.0 h (2.0;4.0) vs. CP-NL 2.0 h (1.0;4.0), P < 0.001]. Patients with CPG showed higher scores for depression [HADS-D, CPG 6.0 (3.0;10.0) vs. CP-NL 5.0 (2.0;8.0), P < 0.001], more impaired quality of life [ItchyQol; CPG: 72.6 (61.6;83.6) vs. CP-NL 59.4 (48.4;70.4), P < 0.001] and higher weighted needs in the predefined treatment goals. DISCUSSION: Not only the presence of severe pruritus and pruriginous lesions but also sleep disorders and other mental symptoms may contribute to a higher burden in patients with CPG when compared with patients with CP-NL.

Long-term survival with modern therapeutic agents against metastatic melanoma-vemurafenib and ipilimumab in a daily life setting.

Despite new therapeutic options, metastatic melanoma remains to be one of the most fatal tumors. With the development of BRAF inhibitors and immune checkpoint inhibitors, overall survival could be prolonged significantly for the first time. Clinical studies implied that even long-term survival is possible with both types of drugs, but predictive markers are so far missing. In this study, we analyzed survival data from patients that received the first-in-class substances vemurafenib and ipilimumab, respectively, during the time period from registration of the drugs until availability of combination treatments. We aimed to evaluate the possibility of long-term survival in a daily life setting and to characterize patients that benefit from these drugs in order to gain insight into predictive attributes. Eighty patients were evaluated who were treated with either vemurafenib (n = 40) or ipilimumab (n = 40), and overall survival was analyzed. Subgroup analysis was performed for patients who were still alive 24 months after induction of therapy (long-term survival). Median overall survival (OS) was 8.0 months for patients treated with vemurafenib and 10.0 months for patients treated with ipilimumab (log-rank P value = 0.689). Long-term survival was achieved in 32.5% of patients (42.3% vemurafenib, 57.7% ipilimumab). Negative predictors of long-term survival in the vemurafenib group were brain and liver metastases, as well as elevated LDH, S100ß and liver enzymes. For ipilimumab, an increase in lymphocytes and eosinophils during course of treatment correlated with long-term survival. Our real-life experience shows that long-term survival is possible with using both therapeutic agents, vemurafenib and ipilimumab. Pattern of metastases and laboratory values might be of interest in decision making for a specific therapeutic approach. Combination of drugs and observational studies in larger patient cohorts are necessary to further validate our findings.

Pretransplant coronary artery disease is a predictor for myocardial infarction and cardiac death after liver transplantation.

BACKGROUND: Cardiovascular disease is a serious problem of liver transplant (LT) recipients because of increased cardiovascular risk due to immunosuppressive therapy, higher age, intraoperative risk and comorbidities (such as diabetes and nicotine abuse). Reported frequency of cardiovascular events after LT shows a high variability between different LT cohorts. Our aim was to analyze a cohort of LT recipients from a single center in Germany to evaluate frequency of the cardiovascular endpoints (CVE) myocardial infarction and/or cardiac death after LT and to investigate correlations of CVE post LT with pretransplant patient characteristics. PATIENTS: In total, data from 352 LT patients were analyzed. Patients were identified from an administrative transplant database, and all data were retrieved from patients' charts and reports. RESULTS: During the median follow-up of 4.0 (0-13) years, 10 cases of CVE were documented (six myocardial infarctions and four coronary deaths). The frequency of CVE did not differ according to classic cardiovascular risk factors such as body mass index (p=0.071), total cholesterol (p=0.533), hypertension (p=0.747), smoking (p=1.000) and pretransplant diabetes mellitus (p=0.146). In patients with pretransplant coronary heart disease (n=24; 6.8%) CVE were found more frequently (p=0.024). CONCLUSION: In summary, we found a rate of 2.8% CVE after LT in a German transplant cohort. Pretransplant CHD was the only risk factor for CVE, but showed no significant impact on overall survival.

Recruiting former melanoma patients via hospitals in comparison to office-based dermatologists in a register-based cohort study that required indirect contact.

BACKGROUND: There are detailed reviews about different recruitment strategies, but not with regard to differences between recruitment of hospital-based versus office-based physicians. Within this study, the two different recruitment schemes are compared. Advantages and disadvantages of different ways of recruitment in registry-based studies are discussed. METHODS: In a cross-sectional cancer-registry-based study, long-term melanoma patients were contacted by dermatologists rather than directly by the registry on the basis of the legal situation. Logistic regression models and generalized estimating equations were used to assess effects of various patient and physician characteristics on participation and data quality. Especially differences between hospital-based versus office-based dermatologists are evaluated. RESULTS: Seventy two out of 112 contacted dermatologists took part in the study (64.3%). The cooperation proportion was 52.2% (689 participants/1320 contacted patients). Participants and non-participants differed regarding age and sex, but not regarding other social demographic factors and cancer stage. We did not observe a difference in patient participation between hospital-based versus office-based dermatologists (OR 1.08 [CI 0.84-1.39]; p = 0.57). However, medical data provided by the cancer registry were better for participants registered and recruited by hospitals. CONCLUSIONS: In cohort studies with epidemiological cancer registries, recruitment via physicians has potential disadvantages and is more complex. If this indirect way of contact is mandatory, we recommend recruitment procedures including hospital-based rather than office-based physicians. However, physician characteristics were not associated with outcome.

Whole-body biodistribution of the cannabinoid type 1 receptor ligand [18F]MK-9470 in the rat.

The endocannabinoid system participates in many processes in the body, including memory, reward, pain, motor activity, food intake, energy metabolism, and gastrointestinal functions. [18F]MK-9470 is a positron emission tomography (PET) ligand that binds with high affinity and selectivity to the cannabinoid type 1 receptor. In order to fully characterize ligand behavior, tracer uptake measured using in vivo microPET was compared with results from ex vivo tissue dissection. Twelve male Sprague-Dawley rats were divided into three subgroups and scanned over time periods of 10min, 30min and 90min using PET. Afterwards, a number of the animals' organs were dissected. Uptake of radioactivity was expressed in terms of %ID/ml and %ID/(g tissue). For comparison of in vivo and ex vivo methods, Bland-Altman plots were computed. The highest uptake of [18F]MK-9470 was found in the liver and small intestine; the brain showed less uptake, while low and unspecific binding was observed in tissue of the heart, lung, kidney and bone. In the brain, normalized uptake of [18F]MK-9470 was on average 0.25%ID/ml (range: 0.16 to 0.28%ID/ml). Bland-Altman plots revealed the best agreement between methods for the 90min acquisition protocols. High hepatic accumulation and metabolism of [18F]MK-9470 occur with mainly enteral excretion, which may vary considerably over time - a finding which may be of relevance in metabolite determination in quantitative brain studies. Comparisons between in vivo and ex vivo methods showed that whole-body distribution of [18F]MK-9470 using positron emission tomography is a preferable alternative to ex vivo biodistribution, and requires a significantly smaller number of animals.

Effects of tetrahydrocannabinol on glucose uptake in the rat brain.

Δ9-Tetrahydrocannabinol (THC) is the psychoactive component of the plant Cannabis sativa and acts as a partial agonist at cannabinoid type 1 and type 2 receptors in the brain. The goal of this study was to assess the effect of THC on the cerebral glucose uptake in the rat brain. 21 male Sprague Dawley rats (12-13 w) were examined and received five different doses of THC ranging from 0.01 to 1 mg/kg. For data acquisition a Focus 120 small animal PET scanner was used and 24.1-28.0 MBq of [18F]-fluoro-2-deoxy-d-glucose were injected. The data were acquired for 70 min and arterial blood samples were collected throughout the scan. THC, THC-OH and THC-COOH were determined at 55 min p.i. Nine volumes of interest were defined, and the cerebral glucose uptake was calculated for each brain region. Low blood THC levels of < 1 ng/ml (injected dose: ≤ 0.01 mg/kg) corresponded to an increased glucose uptake (6-30 %), particularly in the hypothalamus (p = 0.007), while blood THC levels > 10 ng/ml (injected dose: ≥ 0.05 mg/kg) coincided with a decreased glucose uptake (-2 to -22 %), especially in the cerebellar cortex (p = 0.008). The effective concentration in this region was estimated 2.4 ng/ml. This glucose PET study showed that stimulation of CB1 receptors by THC affects the glucose uptake in the rat brain, whereby the effect of THC is regionally different and dependent on dose - an effect that may be of relevance in behavioural studies.