Cutaneous Side Effects of Modern Targeted Therapy and Immunotherapy in Patients with Dermatological Malignancies.

The advent of immunotherapy and targeted therapies in treating dermatological malignancies has dramatically changed the landscape of dermato-oncology in recent years. Their superior efficacy compared to previous therapeutic options, such as chemotherapy, has resulted in their use in treating devastating malignancies, such as melanoma or unresectable/metastatic basal cell and squamous cell carcinoma. Skin toxicity is a critical safety consideration, among other adverse reactions, that can occur under treatment with these agents. This article aims to summarize the cutaneous side effects of immune checkpoint inhibitors and targeted dermato-oncological therapies. Although the skin side effects of these agents are primarily mild, they can occasionally affect the decision for treatment continuation and the quality of life of the affected patients. Therefore, physicians must be acquainted with the specific cutaneous toxicity profile of such treatments to mitigate their impact on the patients and optimize the overall outcome of dermato-oncological therapy.

Shift in Living Kidney Donor Demographics Over the Past 50 Years in a German Transplant Center.

BACKGROUND Living kidney donors may face health risks after donation. Age, sex, body mass index, comorbidities, and relationship to the recipient have an impact on lifetime living kidney donor risk. In view of a changing landscape in renal transplantation with increasing organ shortages, the selection criteria for potential donors may have changed over time. MATERIAL AND METHODS We investigated donor demographics and outcomes in a cohort of 760 living kidney donors who donated from 1967 to 2016 at the transplant center in Heidelberg, Germany. RESULTS The living kidney donor age increased from 34.9±11.5 to 53.2±10.2 years, with 11.4% donors aged 65 years in the period from 2011 to 2016. The number of donors with comorbidities at the time of donation increased. The percentage of donors with a history of obesity, hypertension, smoking, and a family history of kidney disease enlarged to 18.6%, 36.1%, 37.0%, and 9.1%, respectively. De novo hypertension was a common problem in more than half of the donors at long-term follow-up, and donor renal function decreased about 30 mL/mi/1.73 m². CONCLUSIONS This detailed analysis of living kidney donor demographics over the last 50 years detected an increased proportion of donors with higher age and comorbidities today. Careful donor selection, regular follow-up visits, and systematic donor registries are required to further improve donor outcomes.

Neuropsychological functioning in buprenorphine maintained patients versus abstinent heroin abusers on naltrexone hydrochloride therapy.

RATIONALE: Methadone and buprenorphine are among the most widely employed pharmacological treatments currently available for opioid addiction. Cognitive effects of buprenorphine in abstinent heroin abusers are nevertheless far from being understood. METHODS: Neuropsychological performance of 18 buprenorphine-maintained patients (BMP) was evaluated relative to that of 32 currently abstinent heroin abusers on naltrexone hydrochloride therapy (FHAN), and 34 non-drug dependent controls. The three groups were demographically balanced. Clinical groups reported histories of similar patterns of drug use and had increased periods of abstinence from any illicit substance use including heroin. RESULTS: The BMP group performed poorer than controls on the RAVLT (encoding and delayed recall of verbal information), CTT (conceptual flexibility, executive functions) and the RBANS figure copy (visual perception) and delayed recall of visual information. There were no significant differences in any of the cognitive measures between the BMP and FHAN groups or between the FHAN group and controls. Furthermore, the non-differing percentage of abnormal cases between the two patient groups led us to infer that treatment with either BPM or FHAN is not accompanied by qualitative differences in the cognitive profiles of these patients. CONCLUSION: Overall, results suggest that treatment with naltrexone in abstinent heroin abusers may result in less impairment of cognitive functions compared to treatment with buprenorphine. These findings are relevant for improved prognosis and treatment strategies in opioid dependence.

First four Oral Rabies Vaccination campaigns of the red foxes in Greece: Evaluating factors and assessment.

Following the last animal rabies outbreak in Greece in 2012, Oral Rabies Vaccination (ORV) campaigns of red foxes (Vulpes vulpes) were conducted in order to halt the spread of the disease, as widely and effectively have also been implemented in other countries. The present study aims to report the main outcomes following the first Greek ORV campaigns during autumn 2013, 2014, 2015 and spring 2016, to assess their effectiveness and to investigate factors potentially related to their success. Blood samples, mandible bones and teeth, derived by 452 foxes, were tested for rabies antibody titration, animal age determination and tetracycline (TTC) detection. The laboratory results obtained were statistically analyzed. High seroprevalence and TTC detection rates were obtained following the autumn campaigns studied, while these rates were significantly reduced following the spring campaign. The year or the season of the vaccination campaign, the estimated age group of the animal and the geographical Regional Unit (RU), where the animal was hunted, were identified as important factors. On the contrary, no significance could be ascertained for TTC detection based on exclusively previous uptake, use of filter paper, blood sample type and quality, as well as sex of animal. Based on the monitoring results achieved, the first ORV campaigns conducted in the country can be generally considered to be satisfactory. No positives cases were detected since May 2014. Seasonal, geographical parameters and factors related to fox ecology may interfere with monitoring results and should be always considered when planning future ORV programs.

Efficacy of oral rabies vaccination in individual age groups of juvenile red foxes.

Although juvenile red foxes (Vulpes vulpes) are considered a single age group, essential for monitoring the effectiveness of the oral rabies vaccination (ORV), there appear to be significant differences among age subgroups. Herein, a subset of 335 foxes aged 0-1 year that had not consumed bait in previous campaign were collected for monitoring the effectiveness of the first seven ORV campaigns in Greece, carried out from 2013 to 2017. These juveniles were additionally assigned to three individual 4-month age groups, according to the exact date on which they were killed. The aim was to identify differences in seroconversion rate and bait uptake level and determine whether reconsideration is needed in the way that ORV monitoring is being implemented and evaluated. Statistically significant differences were observed following the analysis of mandible bone, teeth and blood samples obtained from 1-4 and 5-8-month old foxes as compared to the respective samples derived from 9-12-month old animals, whereas no differences were revealed in samples between foxes aged 1-4 and 5-8 months. Hunting juveniles during the whole period of spring ORV campaigns monitoring should be reevaluated and even discouraged. On the contrary, juvenile foxes hunted for the evaluation of autumn campaigns, aged > 8 months, had similar assessment rates to adult individuals and are equally helpful for assessing the efficacy of an ORV campaign. Taking the above into consideration and by distinguishing recent and old tetracycline uptake, ORV monitoring and evaluation could be performed in an alternative, more comprehensive way.

The possible effects of the solar and geomagnetic activity on multiple sclerosis.

OBJECTIVES: Increasing observational evidence on the biological effects of Space Weather suggests that geomagnetic disturbances may be an environmental risk factor for multiple sclerosis (MS) relapses. In the present study, we aim to investigate the possible effect of geomagnetic disturbances on MS activity. PATIENTS AND METHODS: MS patient admittance rates were correlated with the solar and geophysical data covering an eleven-year period (1996-2006, 23rd solar cycle). We also examined the relationship of patterns of the solar flares, the coronal mass ejections (CMEs) and the solar wind with the recorded MS admission numbers. RESULTS: The rate of MS patient admittance due to acute relapses was found to be associated with the solar and geomagnetic events. There was a "primary" peak in MS admittance rates shortly after intense geomagnetic storms followed by a "secondary" peak 7-8 months later. CONCLUSION: We conclude that the geomagnetic and solar activity may represent an environmental health risk factor for multiple sclerosis and we discuss the possible mechanisms underlying this association. More data from larger case series are needed to confirm these preliminary results and to explore the possible influence of Space Weather on the biological and radiological markers of the disease.

Thalamic atrophy predicts cognitive impairment in relapsing remitting multiple sclerosis. Effect on instrumental activities of daily living and employment status.

INTRODUCTION: Cognitive impairment is an important predictor of quality of life at all stages of MS. Magnetic Resonance Imaging (MRI) markers have been used to associate tissue damage with cognitive dysfunction. OBJECTIVE: The aim of the study was to designate the MRI marker that predicts cognitive decline and explore its effect on every day activities and employment status. METHODS: 50 RRMS patients and 31 healthy participants underwent neuropsychological assessment using the Trail Making Test (TMT) parts A and B, semantic and phonological verbal fluency task and a computerized cognitive screening battery (Central Nervous System Vital Signs). Everyday activities were evaluated with the instrumental activities of daily living (IADL) scale and employment status. Brain MRI was performed in all participants. We measured total lesion volume, third ventricle width, corpus callosum and thalamic atrophy. RESULTS: The frequency of cognitive dysfunction for our RRMS patients was 38%. RRMS patients differed significantly from controls on the TMTA, TMTB, phonological verbal fluency task, memory, psychomotor speed, reaction time and cognitive flexibility. Neuropsychological measures had a strong correlation with all MRI atrophy measures and a weak or moderate correlation with lesion volume. Psychomotor speed was the most sensitive marker for IADL, while memory and TMTB for employment status. Thalamic area was the most sensitive MRI marker for memory, psychomotor speed and TMTB.. CONCLUSION: Thalamic atrophy predicts the clinically meaningful cognitive decline in our RRMS patients.

Cognitive impairment in relapsing remitting and secondary progressive multiple sclerosis patients: efficacy of a computerized cognitive screening battery.

Objective. To investigate the pattern of cognitive impairment in relapsing remitting multiple sclerosis (RRMS) and secondary progressive multiple sclerosis (SPMS) patients using a computerized battery. Methods. RRMS patients (N = 50), SPMS patients (N = 30), and controls (N = 31) were assessed by Central Nervous System Vital Signs (CNS VS) computerized battery, Trail Making Tests (TMT) A and B, and semantic and phonological verbal fluency tasks. Results. The overall prevalence of cognitive dysfunction was 53.75% (RRMS 38%, SPMS 80%). RRMS patients differed from controls with large effect size on reaction time, medium effect size on TMT A and small on TMT B, phonological verbal fluency, composite memory, psychomotor speed, and cognitive flexibility. SPMS patients differed from controls in all neuropsychological measures (except complex attention) with large effect sizes on TMT A and B, phonological verbal fluency, composite memory, psychomotor speed, reaction time, and cognitive flexibility. Between patient groups, medium effect sizes were present on TMT B and psychomotor speed, while small effect sizes were present on composite memory and processing speed. Conclusion. CNS VS is sensitive in detecting cognitive impairment in RRMS and SPMS patients. Significant impairment in episodic memory, executive function, and processing speed were identified, with gradual increment of the frequency as disease progresses.

Cytokines as Biomarkers of Treatment Response to IFN ß in Relapsing-Remitting Multiple Sclerosis.

Background. MS patients show a remarkable heterogeneity in their response to disease modifying treatments. Given the need for early treatment initiation and the diversity of available options, a predictive marker that indicates good or poor response to treatment is highly desirable. Objective. To find a biomarker for treatment response to IFNß among pro- and anti-inflammatory cytokines. Materials and Methods. IFN-γ, TNF-α, IL-2, IL-4, IL-6, IL-10, IL-17A, and TGF-ß1 levels were measured in serum and CSF of 43 patients with RR-MS who were followed up for a mean period of 5.3 years. Thirty-five patients received IFNß treatment and were divided into good responders (GR, n = 19) and poor responders (PR, n = 16). The remaining 8 patients showed a very favorable outcome and remained untreated (noRx). Results. GR had significantly higher serum baseline levels of IL-17A than PR and significantly higher serum levels of IL-17A, IFN-γ, TNF-α, and IL-2 than noRx. PR had significantly higher IFN-γ serum levels than noRx. No significant differences were observed in serum levels of IL-6, IL-4, IL-10, and TGF-ß1 or the levels of all cytokines measured in CSF between the 3 groups of patients. Conclusions. Baseline serum levels of IL-17A can be used as a biomarker of IFNß treatment response.