A prospective clinical trial to assess lapatinib effects on cutaneous squamous cell carcinoma and actinic keratosis.

BACKGROUND: Antiepidermal growth factor receptor (EGFR)-targeted therapy is widely used in many epithelial cancer types. We investigated lapatinib effects on cutaneous squamous cell carcinoma (cSCC) scheduled for resection and in coexisting precursor lesions (actinic keratosis (AK) and Bowen's disease (BD)) in a phase 2 mode of action clinical trial including a histological workup of the cSCC. PATIENTS AND METHODS: We initiated a prospective single-centre, open-label, non-controlled clinical study with translational intentions to investigate changes in size and histopathological features in cSCC after a 14-day period of neoadjuvant lapatinib therapy at a dose of 1500 mg/day prior to surgery, to quantify the impact on AK and BD in the same patient after 56 days and to evaluate the tolerability in patients with cSCC and precursor lesions. RESULTS: 10 immunocompetent male patients were included with a mean age of 73 years (range 59-87). 8 patients were treated with the study medication lapatinib 1500 mg/day for a total duration of 56 days according to the protocol and were available for full analysis, whereas 2 patients had to discontinue treatment during the first 2 weeks because of adverse events (diarrhoea, pancreatitis). Tolerability was acceptable with only 1 related grade III adverse event. A reduction in tumour size of cSCC was documented in 2 of 8 evaluable patients after 14 days of treatment. The mean regression of captured precursor lesions was 30% after 56 days of treatment and 36% 28 days after therapy cessation. CONCLUSIONS: Short-term lapatinib resulted in a cSCC tumour reduction in 2 of 8 patients. In addition, there was a clinically documented reduction of AK in 7 of 8 patients encouraging larger clinical trials, especially in high-risk patients with cSCC such as organ transplant recipients. TRIAL REGISTRATION NUMBER: NCT0166431.

Watchful Waiting in Continuous-Flow Left Ventricular Assist Device Patients With Ongoing Hemolysis Is Associated With an Increased Risk for Cerebrovascular Accident or Death.

BACKGROUND: Management of hemolysis in the setting of suspected device thrombosis in continuous-flow left ventricular assist device patients varies widely, ranging from watchful waiting with intensified antithrombotic therapy to early surgical device exchange. The aim of this study was to compare the outcomes of hemolysis events treated with surgical interventions versus medical management alone. METHODS AND RESULTS: A retrospective review of Heartmate II continuous-flow left ventricular assist device patients at 2 centers from January 2009 to September 2014 was completed. Patients were categorized as surgical management if hemolysis refractory to intensification of standard antithrombotic therapy was treated surgically. The primary end point was the first occurrence of cerebrovascular accident (CVA) or death. Sixty-four hemolysis events occurred in 49/367 patients implanted with Heartmate II continuous-flow left ventricular assist devices. Of 49 primary hemolysis events, 24 were treated with surgical interventions. After surgical treatment, 1 patient died and 2 experienced CVAs, as compared with 3 deaths and 9 CVAs in the 25 patients who remained on intensified antithrombotic therapy alone. The 1-year freedom from CVA or death was 87.5% and 49.5% in the surgical and medical cohorts, respectively (P=0.027). Resolution of a primary hemolysis event without CVA or death occurred in 21/24 patients treated with surgical interventions and in 13/25 who remained on medical therapy alone. A similar association between treatment and outcome was noted in the 15 recurrent hemolysis events. CONCLUSIONS: Hemolysis refractory to intensification of antithrombotic therapy identifies continuous-flow left ventricular assist device patients at major risk for CVA and death. Early device exchange should be considered to minimize these risks.

Efficacy and safety of oral alitretinoin in severe oral lichen planus--results of a prospective pilot study.

BACKGROUND: Patients with severe oral lichen planus refractory to standard topical treatment currently have limited options of therapy suitable for long-term use. Oral alitretinoin (9-cis retinoic acid) was never systematically investigated in clinical trials, although case reports suggest its possible efficacy. OBJECTIVES: To assess the efficacy and safety of oral alitretinoin taken at 30 mg once daily for up to 24 weeks in the treatment of severe oral lichen planus refractory to standard topical therapy. METHODS: We conducted a prospective open-label single arm pilot study to test the efficacy and safety of 30 mg oral alitretinoin once daily for up to 24 weeks in severe oral lichen planus. Ten patients were included in the study. Primary end point was reduction in signs and symptoms measured by the Escudier severity score. Secondary parameters included pain and quality of life scores. Safety parameters were assessed during a follow-up period of 5 weeks. RESULTS: A substantial response at the end of treatment, i.e. >50% reduction in disease severity measured by the Escudier severity score, was apparent in 40% of patients. Therapy was well tolerated. Adverse events were mild and included headache, mucocutaneous dryness, musculoskeletal pain, increased thyroid-stimulating hormone and dyslipidaemia. CONCLUSIONS: Alitretinoin given at 30 mg daily reduced disease severity of severe oral lichen planus in a substantial proportion of patients refractory to standard treatment, was well tolerated and may thus represent one therapeutic option for this special group of patients.

Altered social and non-social decision-making in recreational and dependent cocaine users.

BACKGROUND: Maladaptive decision-making is assumed to be a core feature of cocaine addiction. Indeed, numerous studies have reported deficits in non-social decision-making tasks and reward-related impulsivity in dependent cocaine users. However, social decision-making has not been examined in cocaine users yet. Moreover, it is unknown if even recreational and non-dependent cocaine use is linked to decision-making deficits. Therefore, we investigated whether recreational and dependent cocaine users exhibit alterations in social and non-social decision-making. METHOD: The performance of healthy controls (n = 68), recreational cocaine users (n = 68) and dependent cocaine users (n = 30) in classical decision-making paradigms (Iowa Gambling Task, Delay Discounting) and in social interaction paradigms (Distribution Game, Dictator Game) was assessed. RESULTS: Decisions in the social interaction tasks of both cocaine user groups were more self-serving compared with controls as cocaine users preferred higher monetary payoffs for themselves. In the Iowa Gambling Task, only dependent cocaine users were more likely to choose disadvantageous card decks, reflecting worse decision-making. They were also more likely to choose immediate smaller rewards over larger delayed rewards in the Delay Discounting task. CONCLUSIONS: Our results imply that both recreational and dependent cocaine users are more concerned with their own monetary gain when interacting with another person. Furthermore, primarily dependent cocaine users are less foresighted and more impulsive regarding immediate reward. Overall, social interaction deficits are already present in recreational users, while non-social decision-making deficits occur predominantly in dependent cocaine users. Thus, social interaction training and cognitive remediation strategies may improve treatment success and quality of life in cocaine dependence.

Primary cutaneous lymphoma: two-decade comparison in a population of 263 cases from a Swiss tertiary referral centre.

BACKGROUND: Epidemiological data on primary cutaneous lymphomas (PCLs) are rare and have not previously been investigated in Switzerland. OBJECTIVE: To analyse variations in demographics, the pattern of subtypes and staging during the two 10-year intervals, 1990-1999 and 2000-2009. METHODS: This was a descriptive study of 263 patients with PCL based on a retrospective review and reassessment according to the World Health Organization/European Organization for Research and Treatment of Cancer classification. RESULTS: Change was observed in the pattern of cutaneous T-cell lymphoma subtypes: the frequency of Sézary syndrome decreased from 17% to 7% and the frequency of CD30+ lymphoproliferative disorders increased from 7% to 18% (overall P = 0·04). Staging of PCL showed a higher number of cases of early-stage mycosis fungoides (P = 0·01). In relation to the international data, the Zürich group had a higher number of patients with Sézary syndrome (11% vs. 3%) and marginal cell lymphoma (14% vs. 5-7%). In addition, comparison of the survival data showed prolonged median overall survival of Zürich patients with Sézary syndrome in the second 10-year interval (6·5 vs. 2-4 years). CONCLUSION: The increasing frequency of marginal cell lymphoma and CD30+ lymphoproliferative disorders might depend on an increased awareness of these diseases in the medical community, driven by progress in the classification and staging of these disease entities.

[Are we treating coronary heart disease and heart failure appropriately in the clinic and ambulatory care? Secondary prevention and drug therapy 1998]. / Therapieren wir die koronare Herzkrankheit und die Herzinsuffizienz in der Klinik und ambulant konsequent? Sekundärprophylaxe und medikamentöse Therapie 1998.

We examined retrospectively 186 patients with acute coronary syndrome (ACS) and 163 patients with cardiac insufficiency (CHF) regarding secondary prevention in hospital or externally. Of the Inhospital-patients with ACS 99% had antithrombotic medicaments (AT), 73% betablockers and 73% a statin. CHF-patients had ACEH in 69%. Externally 120 patients with known coronary heart disease (CHD) received in 91% AT, 66% betablocker, 30% statins and 111 CHF-patients in 49% ACEH. Compared to other studies medical therapy ameliorated in CHD and CHF either stationary and ambulatory. The reasons for low prescription of statins may be due to short time since positive results occurred and to the expensive costs in the setting of pressure because of high cost in health system.

Evidence for age-based rationing in a Swiss university hospital.

AIM: To test the hypothesis that rationing of medical management mainly based on age exists in our health care system today. METHODS: We studied 303 consecutive patients hospitalised for acute coronary syndrome (ACS) and 163 consecutive patients hospitalised with congestive heart failure (CHF). They were divided into two age groups; patients aged less than 75 years and those equal to or older than 75 years. RESULTS: Our main findings were a significant underuse of stress tests (p < 0.001) and coronary angiography (p < 0.0001) in elderly patients with ACS and a significant underuse of echocardiography (p < 0.0001) in patients with CHF of the same age group. In patients with ACS, there was also a trend towards underuse of statins in elderly patients with hypercholesterolaemia. In addition, we noted that the use of beta-blockers in ACS and of ACE inhibitors in CHF was better than in previous published studies but that many patients were still not treated according to evidence based medicine. CONCLUSION: The lower rates of diagnostic tests performed and the lower statin use observed in elderly patients suggest "hidden" rationing of health care in elderly patients.

Carrying behavior in humans: analysis of sex differences.

Behavioral differences between the sexes include methods of carrying books. Females clasp books against their chests; males carry them at their sides. In kindergarten and the first grade, both sexes carry like mature males. Sex-typical carrying appears before adolescence. Behavioral differences seem to be primarily a consequence of morphological differences and social modeling.