Evaluation of organ-specific peripheral doses after 2-dimensional, 3-dimensional and hybrid intensity modulated radiation therapy for breast cancer based on Monte Carlo and convolution/superposition algorithms: implications for secondary cancer risk assessment.

To make a comprehensive evaluation of organ-specific out-of-field doses using Monte Carlo (MC) simulations for different breast cancer irradiation techniques and to compare results with a commercial treatment planning system (TPS). Three breast radiotherapy techniques using 6MV tangential photon beams were compared: (a) 2DRT (open rectangular fields), (b) 3DCRT (conformal wedged fields), and (c) hybrid IMRT (open conformal+modulated fields). Over 35 organs were contoured in a whole-body CT scan and organ-specific dose distributions were determined with MC and the TPS. Large differences in out-of-field doses were observed between MC and TPS calculations, even for organs close to the target volume such as the heart, the lungs and the contralateral breast (up to 70% difference). MC simulations showed that a large fraction of the out-of-field dose comes from the out-of-field head scatter fluence (>40%) which is not adequately modeled by the TPS. Based on MC simulations, the 3DCRT technique using external wedges yielded significantly higher doses (up to a factor 4-5 in the pelvis) than the 2DRT and the hybrid IMRT techniques which yielded similar out-of-field doses. In sharp contrast to popular belief, the IMRT technique investigated here does not increase the out-of-field dose compared to conventional techniques and may offer the most optimal plan. The 3DCRT technique with external wedges yields the largest out-of-field doses. For accurate out-of-field dose assessment, a commercial TPS should not be used, even for organs near the target volume (contralateral breast, lungs, heart).

Prediction of recanalization in acute stroke patients receiving intravenous and endovascular revascularization therapy.

BACKGROUND AND PURPOSE: The study aims to assess the recanalization rate in acute ischemic stroke patients who received no revascularization therapy, intravenous thrombolysis, and endovascular treatment, respectively, and to identify best clinical and imaging predictors of recanalization in each treatment group. METHODS: Clinical and imaging data were collected in 103 patients with acute ischemic stroke caused by anterior circulation arterial occlusion. We recorded demographics and vascular risk factors. We reviewed the noncontrast head computed tomographies to assess for hyperdense middle cerebral artery and its computed tomography density. We reviewed the computed tomography angiograms and the raw images to determine the site and degree of arterial occlusion, collateral score, clot burden score, and the density of the clot. Recanalization status was assessed on recanalization imaging using Thrombolysis in Myocardial Ischemia. Multivariate logistic regressions were utilized to determine the best predictors of outcome in each treatment group. RESULTS: Among the 103 study patients, 43 (42%) received intravenous thrombolysis, 34 (33%) received endovascular thrombolysis, and 26 (25%) did not receive any revascularization therapy. In the patients with intravenous thrombolysis or no revascularization therapy, recanalization of the vessel was more likely with intravenous thrombolysis (P = 0·046) and when M1/A1 was occluded (P = 0·001). In this subgroup of patients, clot burden score, cervical degree of stenosis (North American Symptomatic Carotid Endarterectomy Trial), and hyperlipidemia status added information to the aforementioned likelihood of recanalization at the patient level (P < 0·001). In patients with endovascular thrombolysis, recanalization of the vessel was more likely in the case of a higher computed tomography angiogram clot density (P = 0·012), and in this subgroup of patients gender added information to the likelihood of recanalization at the patient level (P = 0·044). CONCLUSION: The overall likelihood of recanalization was the highest in the endovascular group, and higher for intravenous thrombolysis compared with no revascularization therapy. However, our statistical models of recanalization for each individual patient indicate significant variability between treatment options, suggesting the need to include this prediction in the personalized treatment selection.

The prevalence of erectile dysfunction and its association with antiretroviral therapy in HIV-infected men: the Swiss HIV Cohort Study.

BACKGROUND: Here, we aimed to determine the prevalence of erectile dysfunction (ED) among HIV-infected men and its association with components of antiretroviral therapy. METHODS: Cross-sectional data on sexual dysfunction were collected in the Swiss HIV Cohort Study (SHCS) between December 2009 and November 2010. Multilevel logistic regression models were used to estimate the association between ED and exposure to 24 different antiretroviral drugs from four drug classes. RESULTS: During the study period, 5,194 of 5,539 eligible men in the SHCS had a follow-up visit; 4,064 men answered a question on ED for the first time. Among these men, ED was experienced often by 459 (11%), sometimes by 543 (13%), rarely by 389 (10%), never by 2,526 (62%) and 147 (4%) did not know. ED was associated with older age, an earlier HIV diagnosis and depression. No association was found with any drug class; however, ED was associated with cumulative exposure to either zalcitabine (OR 1.29 per year of use; 95% CI 1.07, 1.55) or enfuvirtide (OR 1.28; 95% CI 1.08, 1.52). CONCLUSIONS: Around 1 in 10 men in the SHCS reported often experiencing ED. We found no association between ED and any drug class, but those exposed to zalcitabine or enfurvitide (drugs no longer or rarely used) were more likely to report ED; this second association was probably not causal.

Therapy of acute massive pulmonary embolism associated with Klippel-Trenaunay syndrome.

Acute massive pulmonary embolism (PE) is a life-threatening event. Before the era of cardiopulmonary bypass, acute pulmonary embolectomy had been historically attempted in patients with severe hemodynamic compromise. The Klippel-Trenaunay syndrome (KTS) represents a significant life-long risk for major thromboembolic events. We present two young patients with Klippel-Trenaunay syndrome who survived surgical embolectomy after massive PE and cardiopulmonary resuscitation, with good postoperative recovery. Even though the role of surgical embolectomy in massive PE is not clearly defined, with current technology it can be life saving and can lead to a complete recovery, especially in young patients as described in this study.

Cell Therapy Assistance in Reconstructive Surgery for Musculoskeletal Tissues Following Burn and Trauma: Swiss Cellular Transplantation Platform

The sterol compositions of three oceanic jellyfish have been determined using gas chromatographic mass spectrometric techniques involving the use of two separate gas chromatographic column systems. The components in overlapping peaks have been identified by comparison of the mass spectra of peaks in the two column systems using subtractive techniques. A mid-water animal, Periphylla periphylla, was found to contain a very complex and unusual sterol profile including rare 5alpha-stanols, whereas two other oceanic jellyfish Pelagia noctiluca and Atolla wyvillei contained similar mixtures of delta5 sterols to those previously isolated from coastal species.

Improving appropriateness of antibiotic therapy: randomized trial of an intervention to foster reassessment of prescription after 3 days.

OBJECTIVES: Reassessment of ongoing antibiotic therapy is an important step towards appropriate use of antibiotics. This study was conducted to evaluate the impact of a short questionnaire designed to encourage reassessment of intravenous antibiotic therapy after 3 days. PATIENTS AND METHODS: Patients hospitalized on the surgical and medical wards of a university hospital and treated with an intravenous antibiotic for 3-4 days were randomly allocated to either an intervention or control group. The intervention consisted of mailing to the physician in charge of the patient a three-item questionnaire referring to possible adaptation of the antibiotic therapy. The primary outcome was the time elapsed from randomization until a first modification of the initial intravenous antibiotic therapy. It was compared within both groups using Cox proportional-hazard modelling. RESULTS: One hundred and twenty-six eligible patients were randomized in the intervention group and 125 in the control group. Time to modification of intravenous antibiotic therapy was 14% shorter in the intervention group (adjusted hazard ratio for modification 1.28, 95% CI 0.99-1.67, P = 0.06). It was significantly shorter in the intervention group compared with a similar group of 151 patients observed during a 2 month period preceding the study (adjusted hazard ratio 1.17, 95% CI 1.03-1.32, P = 0.02). CONCLUSION: The results suggest that a short questionnaire, easily adaptable to automatization, has the potential to foster reassessment of antibiotic therapy.

Dexamethasone therapy and cortisol excretion in severe pediatric head injury.

Glucocorticoids are used in an attempt to reduce brain edema secondary to head injury. Nevertheless, their usefulness remains uncertain and contradictory. In a randomized study of 24 children with severe head injury, urinary free cortisol was measured by radioimmunoassay. Twelve patients (group 1) received dexamethasone and 12 (group 2) did not. All patients were treated with a standardized regimen. In group 1 there was complete suppression of endogenous cortisol production. In group 2 free cortisol was up to 20-fold higher than under basal conditions and reached maximum values on days 1-3. Since the excretion of cortisol in urine reflects the production rate closely and is not influenced by liver function and barbiturates, the results in group 2 show that the endogenous production of steroids is an adequate reaction to severe head injury. Exogenous glucocorticoids are thus unlikely to have any more beneficial effects than endogenous cortisol.

Treg-therapy allows mixed chimerism and transplantation tolerance without cytoreductive conditioning.

Establishment of mixed chimerism through transplantation of allogeneic donor bone marrow (BM) into sufficiently conditioned recipients is an effective experimental approach for the induction of transplantation tolerance. Clinical translation, however, is impeded by the lack of feasible protocols devoid of cytoreductive conditioning (i.e. irradiation and cytotoxic drugs/mAbs). The therapeutic application of regulatory T cells (Tregs) prolongs allograft survival in experimental models, but appears insufficient to induce robust tolerance on its own. We thus investigated whether mixed chimerism and tolerance could be realized without the need for cytoreductive treatment by combining Treg therapy with BM transplantation (BMT). Polyclonal recipient Tregs were cotransplanted with a moderate dose of fully mismatched allogeneic donor BM into recipients conditioned solely with short-course costimulation blockade and rapamycin. This combination treatment led to long-term multilineage chimerism and donor-specific skin graft tolerance. Chimeras also developed humoral and in vitro tolerance. Both deletional and nondeletional mechanisms contributed to maintenance of tolerance. All tested populations of polyclonal Tregs (FoxP3-transduced Tregs, natural Tregs and TGF-beta induced Tregs) were effective in this setting. Thus, Treg therapy achieves mixed chimerism and tolerance without cytoreductive recipient treatment, thereby eliminating a major toxic element impeding clinical translation of this approach.

Impact of previous virological treatment failures and adherence on the outcome of antiretroviral therapy in 2007.

BACKGROUND: Combination antiretroviral treatment (cART) has been very successful, especially among selected patients in clinical trials. The aim of this study was to describe outcomes of cART on the population level in a large national cohort. METHODS: Characteristics of participants of the Swiss HIV Cohort Study on stable cART at two semiannual visits in 2007 were analyzed with respect to era of treatment initiation, number of previous virologically failed regimens and self reported adherence. Starting ART in the mono/dual era before HIV-1 RNA assays became available was counted as one failed regimen. Logistic regression was used to identify risk factors for virological failure between the two consecutive visits. RESULTS: Of 4541 patients 31.2% and 68.8% had initiated therapy in the mono/dual and cART era, respectively, and been on treatment for a median of 11.7 vs. 5.7 years. At visit 1 in 2007, the mean number of previous failed regimens was 3.2 vs. 0.5 and the viral load was undetectable (<50 copies/ml) in 84.6% vs. 89.1% of the participants, respectively. Adjusted odds ratios of a detectable viral load at visit 2 for participants from the mono/dual era with a history of 2 and 3, 4, >4 previous failures compared to 1 were 0.9 (95% CI 0.4-1.7), 0.8 (0.4-1.6), 1.6 (0.8-3.2), 3.3 (1.7-6.6) respectively, and 2.3 (1.1-4.8) for >2 missed cART doses during the last month, compared to perfect adherence. From the cART era, odds ratios with a history of 1, 2 and >2 previous failures compared to none were 1.8 (95% CI 1.3-2.5), 2.8 (1.7-4.5) and 7.8 (4.5-13.5), respectively, and 2.8 (1.6-4.8) for >2 missed cART doses during the last month, compared to perfect adherence. CONCLUSIONS: A higher number of previous virologically failed regimens, and imperfect adherence to therapy were independent predictors of imminent virological failure.

The effect of patient, provider and financing regulations on the intensity of ambulatory physical therapy episodes : a multilevel analysis based on routinely available data

Background: Many studies have found considerable variations in the resource intensity of physical therapy episodes. Although they have identified several patient-and provider-related factors, few studies have examined their relative explanatory power. We sought to quantify the contribution of patients and providers to these differences and examine how effective Swiss regulations are (nine-session ceiling per prescription and bonus for first treatments). Methods: Our sample consisted of 87,866 first physical therapy episodes performed by 3,365 physiotherapists based on referrals by 6,131 physicians. We modeled the number of visits per episode using a multilevel log linear regression with crossed random effects for physiotherapists and physicians and with fixed effects for cantons. The three-level explanatory variables were patient, physiotherapist and physician characteristics. Results: The median number of sessions was nine (interquartile range 6-13). Physical therapy use increased with age, women, higher health care costs, lower deductibles, surgery and specific conditions. Use rose with the share of nine-session episodes among physiotherapists or physicians, but fell with the share of new treatments. Geographical area had no influence. Most of the variance was explained at the patient level, but the available factors explained only 4% thereof. Physiotherapists and physicians explained only 6% and 5% respectively of the variance, although the available factors explained most of this variance. Regulations were the most powerful factors. Conclusion: Against the backdrop of abundant physical therapy supply, Swiss financial regulations did not restrict utilization. Given that patient-related factors explained most of the variance, this group should be subject to closer scrutiny. Moreover, further research is needed on the determinants of patient demand.

Electronic monitoring of compliance to lipid-lowering therapy in clinical practice

Nonadherence to treatment is a common problem in the clinical management of hypercholesterolemic patients. This study was carried out with the aim of monitoring the daily compliance to a 6-month course of lipid-lowering therapy, using a microelectronic device, the Medication Event Monitoring System (MEMS), versus pill count. Forty men with primary hypercholesterolemia were prescribed fluvastatin 1 x 40 mg daily, provided in a MEMS package to record the date and time of each opening of the pillbox. Thirty-nine of 40 patients (98%) completed the study. Total cholesterol and LDL cholesterol levels decreased significantly (18% and 25%, p < 0.001) during the 6-month therapy period. A high mean rate of compliance was achieved by MEMS using the following three indexes--compliance to total prescribed dose (88.8% +/- 13.5%), compliance to prescribed days (82.4% +/- 19.5%), and compliance to prescribed time of day (81.86% +/- 19.5%)--and by pill count (93.4% +/- 9.5%). In addition, the MEMS provided some patterns of nonadherence to medication, undetectable by pill count alone, such as a drug holiday in 38% of cases, a drug omission for more than 7 consecutive days in 9% of cases, and, conversely, use of more than the one prescribed daily dose in 47% of cases. A significant correlation between the rate of compliance and the decrease in LDL cholesterol was observed only when the compliance was assessed by MEMS. The results indicate that MEMS is a useful tool for monitoring compliance in clinical practice and may possibly increase adherence to long-term lipid-lowering therapy.

Limits to potent antiretroviral therapy.

The availability of potent combination antiretroviral therapy (ART), also known as highly active antiretroviral therapy or HAART has changed the prognosis of HIV infection. However, the benefits have to be seen in the context of deficiencies of current therapy: failure to eradicate the virus, the slow and potentially incomplete recovery of the immune system, the high prevalence of resistance, and the potential for long-term toxicity. Treatment strategies need to take into account these limits to better target those HIV-infected patients who could benefit the most from antiretroviral therapy.

Anti-TNF Therapy in the Treatment of Psoriasis in a Patient with Acute-on-Chronic Pancreatitis.

Background: Psoriasis is accepted as a multisystemic disease with several important systemic manifestations. Thus, underlying comorbidities have to be taken into account in the choice of treatment. Objective: To explore the role of anti-TNF therapy in the treatment of psoriasis in a patient with acute-on-chronic pancreatitis. Methods: Here, we present the case of a 75-year-old patient with severe psoriasis also suffering from chronic alcohol-induced pancreatitis with recurrent acute flares. A recent life-threatening episode of acute pancreatitis and ischemic liver precluded the reintroduction of methotrexate. Cyclosporine was also excluded as it has been reported to induce acute pancreatitis. Thus, an anti-TNF treatment was initiated in close collaboration with a gastroenterologist. Results: A year after starting anti-TNF therapy the patient continues to show complete clinical remission of his psoriasis. No side effects, particularly no bacterial infections, were reported. No relapses of the patient's underlying chronic pancreatitis were observed throughout the entire treatment with regular clinical and laboratory monitoring, suggesting that chronic pancreatitis is not per se a contraindication for anti-TNF therapy. Conclusion: This case study opens the way for further questioning on the role of TNF in the pathogenesis of chronic and acute pancreatitis and the use of anti-TNF therapy in its treatment. © 2013 S. Karger AG, Basel.