Long-term trends in hepatitis C prevalence, treatment uptake and liver-related events in the Swiss HIV Cohort Study.

BACKGROUND AND AIMS: Treatment for chronic hepatitis C virus (HCV) infections changed dramatically in the last decade. We assessed changes in the prevalence of replicating HCV infection, treatment uptake and liver-related morbidity and mortality in persons with HIV (PWH) and hepatitis C in the Swiss HIV cohort study. METHODS: We included all cohort participants between 2002 and 2021. We assessed yearly prevalence of replicating HCV infection, overall and liver-related mortality, as well as the yearly incidence of liver-related events in persons with at least one documented positive HCV-RNA. RESULTS: Of 14 652 participants under follow-up, 2294 had at least one positive HCV-RNA measurement. Of those, 1316 (57%) ever received an HCV treatment. Treatment uptake increased from 8.1% in 2002 to a maximum of 32.6% in 2016. Overall, prevalence of replicating HCV infection declined from 16.5% in 2004 to 1.3% in 2021. HCV prevalence declined from 63.2% to 7.1% in persons who inject drugs, and from 4.1% to 0.6% in men who have sex with men. Among the 2294 persons with replicating HCV infection, overall mortality declined from a maximum of 3.3 per 100 patient-years (PY) to 1.1 per 100 PY, and incidence of liver-related events decreased from 1.4/100 PY to 0.2/100 PY. CONCLUSIONS: The introduction of DAA therapy was associated with a more than 10-fold reduction in prevalence of replicating HCV infection in PWH, approaching the estimates in the general population. Overall mortality and liver-related events declined substantially in persons living with HIV and hepatitis C.

Prevalence and influencing factors for artifact development in breast MRI-derived maximum intensity projections.

BACKGROUND: Magnetic resonance imaging (MRI) provides high diagnostic sensitivity for breast cancer. However, MRI artifacts may impede the diagnostic assessment. This is particularly important when evaluating maximum intensity projections (MIPs), such as in abbreviated MRI (AB-MRI) protocols, because high image quality is desired as a result of fewer sequences being available to compensate for problems. PURPOSE: To describe the prevalence of artifacts on dynamic contrast enhanced (DCE) MRI-derived MIPs and to investigate potentially associated attributes. MATERIAL AND METHODS: For this institutional review board approved retrospective analysis, MIPs were generated from subtraction series and cropped to represent the left and right breasts as regions of interest. These images were labeled by three independent raters regarding the presence of MRI artifacts. MRI artifact prevalence and associations with patient characteristics and technical attributes were analyzed using descriptive statistics and generalized linear models (GLMMs). RESULTS: The study included 2524 examinations from 1794 patients (median age 50 years), performed on 1.5 and 3.0 Tesla MRI systems. Overall inter-rater agreement was kappa = 0.54. Prevalence of significant unilateral artifacts was 29.2% (736/2524), whereas bilateral artifacts were present in 37.8% (953/2524) of all examinations. According to the GLMM, artifacts were significantly positive associated with age (odds ratio [OR] = 1.52) and magnetic field strength (OR = 1.55), whereas a negative effect could be shown for body mass index (OR = 0.95). CONCLUSION: MRI artifacts on DCE subtraction MIPs of the breast, as used in AB-MRI, are a relevant topic. Our results show that, besides the magnetic field strength, further associated attributes are patient age and body mass index, which can provide possible targets for artifact reduction.

Publication rate and research topics of studies in pediatric kidney transplantation.

BACKGROUND: The quality of medical care for pediatric kidney transplant recipients depends on sound evidence from published clinical trials. METHODS: We examined the publication rate, time to publication, and factors associated with publication of studies in pediatric kidney transplantation registered on ClinicalTrials.gov from 1999 to 2020. RESULTS: We identified 136 studies with an overall enrollment of 36255 study participants, of which only 58.8% have been published yet. Unpublished studies included data from 14 350 participants. The median time to publication was 25 months (range, 0-117) with a significantly shorter time to publication in more recent years. The most frequently investigated research topic was immunosuppressants (49.3%), followed by perioperative management (11.0%) and infectiology (10.3%). The percentage of published studies was highest for the topic steroid withdrawal (87.5%), followed by infectiology (78.6%), and nutrition, sports and quality of life (71.4%). Studies, which were co-funded by industry, showed a significantly higher 5-year publication rate (p = 0.019). CONCLUSIONS: In conclusion, nearly half of all studies in pediatric kidney transplantation remain unpublished. Non-publication of studies might lead to a publication bias with a negative impact on clinical decision-making.

Timing of reconstruction of the lower urinary tract in pediatric kidney transplant recipients: A CERTAIN multicenter analysis of current practice.

BACKGROUND: Preexistent LUTD are considered a hostile environment, which might negatively impact KTx survival. In such cases, surgical reconstruction of the bladder is required. However, there is still disagreement on the optimal timing of the reconstruction procedure. METHODS: This is a multicenter analysis of data from the CERTAIN Registry. Included were 62 children aged 8.18 ± 4.90 years, with LUTD. Study endpoints were the duration of initial posttransplant hospitalization, febrile UTIs, and a composite failure endpoint comprising decline of eGFR, graft loss, or death up to 5 years posttransplant. Outcome was compared to matched controls without bladder dysfunction. RESULTS: Forty-one patients (66.1%) underwent pretransplant and 14 patients (22.6%) posttransplant reconstruction. Bladder augmentation was performed more frequently in the pretransplant (61%) than in the posttransplant group (21%, p = .013). Outcome in the pre- and posttransplant groups and in the subgroups of patients on pretransplant PD with major bladder surgery either pre- (n = 14) or posttransplant (n = 7) was comparable. Outcomes of the main study cohort and the matched control cohort (n = 119) were comparable during the first 4 years posttransplant; at year 5, there were more events of transplant dysfunction in the study cohort with LUTD than in controls (p = .03). CONCLUSIONS: This multicenter analysis of the current practice of LUTD reconstruction in pediatric KTx recipients shows that pre- or posttransplant surgical reconstruction of the lower urinary tract is associated with a comparable 5-year outcome.

Pregnancy with inflammatory bowel disease: Outcomes for mothers and their children at a European tertiary care center.

AIM: The study aimed at investigating pregnancy complications, birth outcomes, and postnatal child development in pregnancies of women with inflammatory bowel diseases (IBDs). METHODS: This is an uncontrolled retrospective single-center study between 2014 and 2019. It is a mixed-method cross-sectional study using data from (1) electronic patient records and (2) questionnaires and copies of mothers' and children's health booklets. Disease activity and IBD medications were analyzed and related to pregnancy complications, birth outcomes, and postnatal child development using mixed models for statistical analyses. RESULTS: Fifty live births from 46 patients were included. Disease activity anytime during pregnancy occurred in 56%. Biologics were applied in ca. 25% of pregnancies, mostly only through the second trimester. Pregnancies of mothers with active disease were slightly shorter than those of mothers with inactive disease (37.4 weeks vs. 38.9 weeks). Adverse pregnancy outcomes were reported in 28% of the live births, including small for gestational age in 6%, low birth weight in 18%, and preterm birth in 20%. Postnatal developmental abnormalities and health problems were reported in 26.8% of the children. Mixed model analyses failed to reveal significant associations between IBD activity and IBD medications during pregnancy and pregnancy complications, perinatal birth outcomes, and postnatal child development. CONCLUSION: Despite a tendency of shorter pregnancies in patients with active IBD and lower birth weight and birth size in patients with IBD-related therapy during pregnancy, disease activity and medications did not significantly influence pregnancy, birth, and developmental outcomes.

Potential of blood-based biomarker approaches in endometrium and breast cancer: a case-control comparison study.

PURPOSE: Endometrial carcinoma is the second most common gynecological malignancy. Until today lacking a screening tool. A blood-based biomarker could help address this need. METHODS: The expression levels of 30 acylcarnitines, 18 amino acids, 6 miRNAs, and 7 DNA methylation sites were measured in blood samples from 331 women (20 EC, 14 benign uterine lesions (benign), 140 breast cancers (BC), 157 controls). Areas under the ROC curves (AUC), sensitivity (sens.) and specificity (spec.) were computed to identify the variables best distinguishing. RESULTS: The best top ten markers for the four comparisons (cancer vs. cancer-free; EC vs. BC, EC vs. controls; EC vs. benign), were identified via AUC. Malonylcarnitine distinguished best patients with EC from controls (AUC: 0.827, sens. 80%, spec. 73.1%) or BC (AUC: 0.819, sens. 84.3%, spec. 80%) being most notable. Tryptophan best differentiated benign from EC (AUC: 0.846, sens. 70%, spec. 92.9%). CONCLUSIONS: The levels of the analyzed blood markers yielded promising results in the detection of EC and warrant further evaluation.

Monotonicity conditions for avoiding counterintuitive decisions in basket trials.

In a basket trial, a new treatment is tested in different subgroups, called the baskets. In oncology, the baskets usually comprise patients with different primary tumor sites but a common biomarker. Most basket trials are uncontrolled phase II trials and investigate a binary endpoint such as tumor response. To combine the data of baskets that show a similar response to the treatment, many basket trial designs use Bayesian borrowing methods. This increases the power compared to a basketwise analysis. However, it can lead to posterior probabilities that are not monotonically increasing in the number of responses. We show that, as a consequence, two types of counterintuitive decisions can arise-one that occurs within a single trial and one that occurs when the results are compared between different trials. We propose two monotonicity conditions for the inference in basket trials. Using a design recently proposed by Fujikawa and colleagues, we investigate the case of a single-stage basket trial with equal sample sizes in all baskets and show that, as the number of baskets increases, these conditions are violated for a wide range of different borrowing strengths. We show that in the investigated scenarios pruning baskets can help to ensure that the monotonicity conditions hold and investigate how this affects type I error rate and power.

Outbreaks of publications about emerging infectious diseases: the case of SARS-CoV-2 and Zika virus.

BACKGROUND: Outbreaks of infectious diseases generate outbreaks of scientific evidence. In 2016 epidemics of Zika virus emerged, and in 2020, a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a pandemic of coronavirus disease 2019 (COVID-19). We compared patterns of scientific publications for the two infections to analyse the evolution of the evidence. METHODS: We annotated publications on Zika virus and SARS-CoV-2 that we collected using living evidence databases according to study design. We used descriptive statistics to categorise and compare study designs over time. RESULTS: We found 2286 publications about Zika virus in 2016 and 21,990 about SARS-CoV-2 up to 24 May 2020, of which we analysed a random sample of 5294 (24%). For both infections, there were more epidemiological than laboratory science studies. Amongst epidemiological studies for both infections, case reports, case series and cross-sectional studies emerged first, cohort and case-control studies were published later. Trials were the last to emerge. The number of preprints was much higher for SARS-CoV-2 than for Zika virus. CONCLUSIONS: Similarities in the overall pattern of publications might be generalizable, whereas differences are compatible with differences in the characteristics of a disease. Understanding how evidence accumulates during disease outbreaks helps us understand which types of public health questions we can answer and when.

Role of fecal calprotection in predicting endoscopic recurrence in postoperative Crohn's disease.

BACKGROUND AND AIMS: Fecal calprotectin (fCP) has been shown to correlate with endoscopic disease activity in Crohn's disease (CD). The aim of this study was to evaluate its role in predicting early endoscopic recurrence in postoperative CD. METHODS: Patients who underwent CD-related intestinal resection with ileocolonic anastomosis were prospectively followed up until ileocolonoscopy was performed around 12 months post-surgery. Endoscopic recurrence (ER) was defined as modified Rutgeerts score i2b or higher. Endoscopic still images were reviewed by 2 independent reviewers blinded to fCP results. Stool specimens were collected 6 months post-surgery and a multivariate logistic regression model was established to explore the predictive value of fCP for ER. RESULTS: 79 patients were included. FCP was significantly associated with endoscopic recurrence (p = .036). A cut-off value of fCP of 267 µg/g at 6 months post-surgery predicted ER with a sensitivity of 61.8% and a specificity of 72.7% (AUC 0.669). A prediction model subsuming age at diagnosis and fCP 6 months post-surgery were significantly associated with ER (fCP at 6 months [p = .007] and age at diagnosis [p = .004], multivariate analysis). CONCLUSIONS: FCP 6 months after surgery and age at diagnosis predict early ER at 1 year postoperatively. However, the low sensitivity of fCP still suggests the necessity of endoscopy as a gold standard for the assessment of postoperative recurrence of CD.KEY SUMMARYWhat is already known? Fecal calprotectin (fCP) correlates with endoscopic disease activity. Endoscopic recurrence occurs in up to 70% of patients after intestinal resection within 1 year.What are the significant and/or new findings of this study? Fecal calprotectin 6 months post-surgery and age at diagnosis significantly predict endoscopic recurrence at 1 year. Due to low sensitivity fCP cannot replace the necessity of endoscopy for accurate assessment of postoperative recurrence.

INVESTIGATING A GROWTH PREDICTION MODEL IN ADVANCED AGE-RELATED MACULAR DEGENERATION WITH SOLITARY GEOGRAPHIC ATROPHY USING QUANTITATIVE AUTOFLUORESCENCE.

PURPOSE: To investigate geographic atrophy (GA) progression using quantitative autofluorescence (qAF) in eyes with solitary GA. METHODS: Forty-three eyes of 26 patients (age 79.7 ± 7.2 years; 28 women; 16 pseudophakic) underwent spectral-domain optical coherence tomography and qAF imaging at baseline and after 12 months. The junctional zone (AJZ) and a nonaffected 300-µm-wide control area (AC) were delineated on spectral-domain optical coherence tomography scans and transferred to the qAF image. Linear mixed models were calculated to investigate the association between GA progression and qAF, age, and baseline GA area. Mixed model analyses of variance were used to investigate differences in qAF between areas. RESULTS: Quantitative autofluorescence of the three inferior sections of both the AJZ (P = 0.028; P = 0.014 and P = 0.032) and the AC (P = 0.043; P = 0.02 and P = 0.028) were significantly associated with GA progression after 12 months. However, qAF measurements were not associated with GA progression in the overall model (P > 0.05). Mean qAF was significantly lower in the AJZ and growth area (AG12) than in the AC (both P ≤ 0.001). CONCLUSION: The authors report a statistically significant association between GA growth area and qAF measurements at specific retinal locations and a significant difference in qAF between the GA border and unaffected areas outside the lesion. Quantitative autofluorescence measurements may be limitedly useful for predicting GA progression.

Mycoplasma genitalium incidence, persistence, concordance between partners and progression: systematic review and meta-analysis.

BACKGROUND: Mycoplasma genitalium is increasingly seen as an emerging sexually transmitted pathogen, and has been likened to Chlamydia trachomatis, but its natural history is poorly understood. The objectives of this systematic review were to determine M. genitalium incidence, persistence, concordance between sexual partners and the risk of pelvic inflammatory disease (PID). METHODS: We searched Medline, EMBASE, LILACS, IndMed and African Index Medicus from 1 January 1981 until 17 March 2018. Two independent researchers screened studies for inclusion and extracted data. We examined results in forest plots, assessed heterogeneity and conducted meta-analysis where appropriate. Risk of bias was assessed for all studies. RESULTS: We screened 4634 records and included 18 studies; six (4201 women) reported on incidence, five (636 women) on persistence, 10 (1346 women and men) on concordance and three (5139 women) on PID. Incidence in women in two very highly developed countries was 1.07 per 100 person-years (95% CI 0.61 to 1.53, I2 0%). Median persistence of M. genitalium was estimated from one to three months in four studies but 15 months in one study. In 10 studies measuring M. genitalium infection status in couples, 39%-50% of male or female sexual partners of infected participants also had M. genitalium detected. In prospective studies, PID incidence was higher in women with M. genitalium than those without (risk ratio 1.73, 95% CI 0.92 to 3.28, I2 0%, two studies). DISCUSSION: Incidence of M. genitalium in very highly developed countries is similar to that for C. trachomatis, but concordance might be lower. Taken together with other evidence about age distribution and antimicrobial resistance in the two infections, M. genitalium is not the new chlamydia. Synthesised data about prevalence, incidence and persistence of M. genitalium infection are inconsistent. These findings can be used for mathematical modelling to investigate the dynamics of M. genitalium. REGISTRATION NUMBERS: CRD42015020420, CRD42015020405.

Screening for post-traumatic stress disorders in 1017 cancer patients and correlation with anxiety, depression, and distress.

OBJECTIVE: Post-traumatic stress disorder (PTSD) is a severe psychiatric disorder, which might develop after a traumatic event, like cancer diagnosis, and threatens the patient's psychological and/or physiological integrity. Anxiety, depression, and mental distress are known to be common in cancer patients; however, the frequency of PTSD was not investigated thoroughly in this patient group so far. Here, we aim to screen cancer patients for PTSD symptoms and determine a possible correlation with anxiety, depression, and distress. METHODS: The study was performed at the Divisions of Hematology and Oncology of the Medical University of Vienna from 2010 to 2018. Following written consent, patients were asked to fill out the validated self-assessment questionnaire for PTSS-10 and HADS. The study was approved by the institutional ethics committee of the Medical University of Vienna (EC Nr: 2255/2016). RESULTS: A total of 1017 adult cancer patients (513 male, 504 female) were included in a cross-sectional single-center study. Mean age was 57.6 years (SD 14.4 years); 31.7%, 14.6%, 13.2%, and 27.4% of patients outscored the predefined thresholds for self-assessed cases of PTSD, anxiety, depression, and distress, respectively. Compared with men, women showed a higher prevalence of symptoms for PTSD (38.9% vs 24.5%; P < .001) and anxiety (20.4% vs 8.6%; P < .001). The scores of HADS-A, HADS-D, and the combined HADS score (distress) were significantly correlated with PTSS-10 scores (P < .01). No differences in age were observed among the different score groups. CONCLUSION: The study shows a significant prevalence as well as a correlation of PTSD symptoms with anxiety, depression, and distress among cancer patients. Findings underscore the necessity of a serious screening for psychiatric disorders, especially in female patients. In order to enable multidisciplinary care for cancer patients and to reduce the burden for psychiatric disorders, interdisciplinary screening and treatment concepts, which take into account gender aspects, are urged.

A Randomized Trial of Bortezomib in Late Antibody-Mediated Kidney Transplant Rejection.

Late antibody-mediated rejection (ABMR) is a leading cause of kidney allograft failure. Uncontrolled studies have suggested efficacy of the proteasome inhibitor bortezomib, but no systematic trial has been undertaken to support its use in ABMR. In this randomized, placebo-controlled trial (the Bortezomib in Late Antibody-Mediated Kidney Transplant Rejection [BORTEJECT] Trial), we investigated whether two cycles of bortezomib (each cycle: 1.3 mg/m2 intravenously on days 1, 4, 8, and 11) prevent GFR decline by halting the progression of late donor-specific antibody (DSA)-positive ABMR. Forty-four DSA-positive kidney transplant recipients with characteristic ABMR morphology (median time after transplant, 5.0 years; pretransplant DSA documented in 19 recipients), who were identified on cross-sectional screening of 741 patients, were randomly assigned to receive bortezomib (n=21) or placebo (n=23). The 0.5-ml/min per 1.73 m2 per year (95% confidence interval, -4.8 to 5.8) difference detected between bortezomib and placebo in eGFR slope (primary end point) was not significant (P=0.86). We detected no significant differences between bortezomib- and placebo-treated groups in median measured GFR at 24 months (33 versus 42 ml/min per 1.73 m2; P=0.31), 2-year graft survival (81% versus 96%; P=0.12), urinary protein concentration, DSA levels, or morphologic or molecular rejection phenotypes in 24-month follow-up biopsy specimens. Bortezomib, however, associated with gastrointestinal and hematologic toxicity. In conclusion, our trial failed to show that bortezomib prevents GFR loss, improves histologic or molecular disease features, or reduces DSA, despite significant toxicity. Our results reinforce the need for systematic trials to dissect the efficiency and safety of new treatments for late ABMR.

Prevalence of Mycoplasma genitalium in different population groups: systematic review andmeta-analysis.

BACKGROUND: Mycoplasma genitalium is a common cause of non-gonococcal non-chlamydial urethritis and cervicitis. Testing of asymptomatic populations has been proposed, but prevalence in asymptomatic populations is not well established. We aimed to estimate the prevalence of M. genitalium in the general population, pregnant women, men who have sex with men (MSM), commercial sex workers (CSWs) and clinic-based samples, METHODS: We searched Embase, Medline, IndMED, African Index Medicus and LILACS from 1 January 1991 to 12 July 2016 without language restrictions. We included studies with 500 participants or more. Two reviewers independently screened and selected studies and extracted data. We examined forest plots and conducted random-effects meta-analysis to estimate prevalence, if appropriate. Between-study heterogeneity was examined using the I2 statistic and meta-regression. RESULTS: Of 3316 screened records, 63 were included. In randomly selected samples from the general population, the summary prevalence was 1.3% (95% CI 1.0% to 1.8%, I2 41.5%, three studies, 9091 people) in countries with higher levels of development and 3.9% (95% CI 2.2 to 6.7, I2 89.2%, three studies, 3809 people) in countries with lower levels. Prevalence was similar in women and men (P=0.47). In clinic based samples, prevalence estimates were higher, except in asymptomatic patients (0.8%, 95% CI 0.4 to 1.4, I2 0.0%, three studies, 2889 people). Summary prevalence estimates were, in the following groups: pregnant women 0.9% (95% CI 0.6% to 1.4%, I2 0%, four studies, 3472 people), MSM in the community 3.2% (95% CI 2.1 to 5.1, I2 78.3%, five studies, 3012 people) and female CSWs in the community 15.9% (95% CI 13.5 to 18.9, I2 79.9%, four studies, 4006 people). DISCUSSION: This systematic review can inform testing guidelines for M. genitalium. The low estimated prevalence of M. genitalium in the general population, pregnant women and asymptomatic attenders at clinics does not support expansion of testing to these groups. REGISTRATION NUMBERS: PROSPERO: CRD42015020420.

Feasibility of personalized treatment concepts in gastrointestinal malignancies: Sub-group results of prospective clinical phase II trial EXACT.

OBJECTIVE: Advances in high-throughput genomic profiling and the development of new targeted therapies improve patient's survival. In gastrointestinal (GI) malignancies, the concept of personalized medicine (PM) was not investigated so far. The aim of this prospective study was to evaluate the efficacy of a personalized treatment in GI patients who failed standard treatment. METHODS: Out of the original prospective clinical phase II EXACT trial, 21 (38%) GI cancer patients who had no further treatment options were identified. A molecular profile (MP) via a 50 gene next generation sequencing (NGS) panel in combination with immunohistochemistry (IHC) was conducted using real-time biopsy tumor material. Results were discussed by a multidisciplinary team (MDT) to translate the individual MP in an experimental treatment. RESULTS: Of the 55 patients originally included in the EXACT trial, 21 (38%) suffered from GI malignancies. The final analysis showed that 15 (71%) patients had experienced a longer progression-free survival (PFS) upon experimental targeted treatment (124 d, quartiles 70/193 d), when compared with the PFS achieved by the previous conventional therapy (62 d, quartiles 55/83 d) (P=0.014). Thirteen (62%) patients receiving targeted treatment experienced a disease control according to Response Evaluation Criteria in Solid Tumors (RECIST). Median overall survival (OS) from the start of experimental therapy to time of censoring or death was 193 d (quartiles 115/374 d). CONCLUSIONS: PM was not investigated in GI malignancies so far in a prospective trial. This study shows that treatment based on real-time molecular tumor profiling led to a superior clinical benefit, and survival as well as response was significantly improved when compared with previous standard medications.

Influence of multiple stapler firings used for rectal division on colorectal anastomotic leak rate.

BACKGROUND: Anastomotic leakage following colorectal resection remains one of the most significant complications with relevant morbidity and mortality. There is evidence that a higher number of stapler firings for rectal division can affect the leak rate in double stapling anastomosis. However, there are no data concerning compression anastomosis. We present our institutional experience addressing this issue. DESIGN: This is a retrospective review of a prospective institutional database of patients undergoing colonic and rectal resection for benign and malignant indications between January 2008 and December 2014 at the surgical department of the St. John of God Hospital, Vienna. Inclusion criteria were rectal division with linear stapling devices and construction of anastomosis to the rectal stump using a circular stapler or compression device. RESULTS: Three hundred eighty two (196 female; 51.3%) patients were included. Mean age was 65.8 years (range: 18-95) Indications for the operation included diverticular disease (44.8%), colorectal carcinoma (51.6%), inflammatory bowel disease (1.8%), and adenoma (1.8%). A laparoscopic approach was employed in 334 cases (87.4%); in 170 patients (44.9%), a compression anastomosis was created. One, two, and three or more stapler cartridges were used for rectal division in 58.4, 33.5, and 8.1%, respectively. Male gender, neoadjuvant therapy, rectal cancer as an underlying disease, laparoscopic surgical approach, and duration of operation longer than 200 min are leading causes for the usage of more than one stapler cartridge. Overall leak rate was 4.7% (18/382). The only factor associated with the occurrence of leakage was the use of three or more stapler cartridges for the closure of the rectal stump (p = 0.002). CONCLUSION: Our data support that multiple stapler firings for rectal division following colorectal resection has a major impact on anastomotic leak rate. Especially in laparoscopic surgery efforts should be made to minimize the number of stapler cartridges used.

Sevoflurane attenuates systemic inflammation compared with propofol, but does not modulate neuro-inflammation: A laboratory rat study.

BACKGROUND: Septic encephalopathy is believed to be a result of neuro-inflammation possibly triggered by endotoxins, such as lipopolysaccharides (LPS). Modulation of the immune system is a property of volatile anaesthetics. OBJECTIVE: We aimed to investigate the systemic and cerebral inflammatory response in a LPS-induced sepsis model in rats. We compared two different sedation strategies, intravenous propofol and the volatile anaesthetic sevoflurane, with the hypothesis that the latter may attenuate neuro-inflammatory processes. DESIGN: Laboratory rat study. SETTING: Basic research laboratories at the University Hospital Zurich and University Zurich Irchel between August 2014 and June 2016. PATIENTS: A total of 32 adult male Wistar rats. INTERVENTIONS: After tracheotomy and mechanical ventilation, the anaesthetised rats were monitored before sepsis was induced by using intravenous LPS or phosphate-buffered saline as control. Rats were sedated with propofol (10 mg kg h) or sevoflurane (2 vol%) continuously for 12 h. MAIN OUTCOME MEASURES: Systemic inflammatory markers such as cytokine-induced neutrophil chemo-attractant protein 1, monocyte chemo-tactic protein-1 and IL-6 were determined. The same cytokines were measured in brain tissue. Cellular response in the brain was assessed by defining neutrophil accumulation with myeloperoxidase and also activation of microglia with ionised calcium-binding adaptor molecule-1 and astrocytes with glial fibrillary acidic protein. Finally, brain injury was determined. RESULTS: Animals were haemodynamically stable in both sedation groups treated with LPS. Blood cytokine peak values were lower in the sevoflurane-LPS compared with propofol-LPS animals. In brain tissue of LPS animals, chemoattractant protein-1 was the only significantly increased cytokine (P = 0.003), however with no significance between propofol and sevoflurane. After LPS challenge, cerebral accumulation of neutrophils was observed. Microglia activation was pronounced in the hippocampus of animals treated with LPS (P = 0.006). LPS induced prominent astrogliosis (P < 0.001). There was no significant difference in microglia or astrocyte activation or apoptosis in the brain between sevoflurane and propofol. CONCLUSION: We have shown that systemic attenuation of inflammation by the volatile anaesthetic sevoflurane did not translate into attenuated neuro-inflammation in this LPS-induced inflammation model. TRIAL REGISTRATION: Animal approval No. 134/2014, Veterinäramt Zürich.

ATRP-based synthesis and characterization of light-responsive coatings for transdermal delivery systems.

The grafting of poly(hydroxyethylmethacrylate) on polymeric porous membranes via atom transfer radical polymerization (ATRP) and subsequent modification with a photo-responsive spiropyran derivative is described. This method leads to photo-responsive membranes with desirable properties such as light-controlled permeability changes, exceptional photo-stability and repeatability of the photo-responsive switching. Conventional track etched polyester membranes were first treated with plasma polymer coating introducing anchoring groups, which allowed the attachment of ATRP-initiator molecules on the membrane surface. Surface initiated ARGET-ATRP of hydroxyethylmethacrylate (where ARGET stands for activator regenerated by electron transfer) leads to a membrane covered with a polymer layer, whereas the controlled polymerization procedure allows good control over the thickness of the polymer layer in respect to the polymerization conditions. Therefore, the final permeability of the membranes could be tailored by choice of pore diameter of the initial membranes, applied monomer concentration or polymerization time. Moreover a remarkable switch in permeability (more than 1000%) upon irradiation with UV-light could be achieved. These properties enable possible applications in the field of transdermal drug delivery, filtration, or sensing.

Dosimetric benefit of online treatment plan adaptation in stereotactic ultrahypofractionated MR-guided radiotherapy for localized prostate cancer.

Background: Apart from superior soft tissue contrast, MR-guided stereotactic body radiation therapy (SBRT) offers the chance for daily online plan adaptation. This study reports on the comparison of dose parameters before and after online plan adaptation in MR-guided SBRT of localized prostate cancer. Materials and methods: 32 consecutive patients treated with ultrahypofractionated SBRT for localized prostate cancer within the prospective SMILE trial underwent a planning process for MR-guided radiotherapy with 37.5 Gy applied in 5 fractions. A base plan, derived from MRI simulation at an MRIdian Linac, was registered to daily MRI scans (predicted plan). Following target and OAR recontouring, the plan was reoptimized based on the daily anatomy (adapted plan). CTV and PTV coverage and doses at OAR were compared between predicted and adapted plans using linear mixed regression models. Results: In 152 out of 160 fractions (95%), an adapted radiation plan was delivered. Mean CTV and PTV coverage increased by 1.4% and 4.5% after adaptation. 18% vs. 95% of the plans had a PTV coverage ≥95% before and after online adaptation, respectively. 78% vs. 100% of the plans had a CTV coverage ≥98% before and after online adaptation, respectively. The D0.2cc for both bladder and rectum were <38.5 Gy in 93% vs. 100% before and after online adaptation. The constraint at the urethra with a dose of <37.5 Gy was achieved in 59% vs. 93% before and after online adaptation. Conclusion: Online adaptive plan adaptation improves target volume coverage and reduces doses to OAR in MR-guided SBRT of localized prostate cancer. Online plan adaptation could potentially further reduce acute and long-term side effects and improve local failure rates in MR-guided SBRT of localized prostate cancer.