Fluorescence Lifetime Imaging Microcopy of Extravasating Cancer Cells in the Mouse Microenvironment

Objective. To determine (i) whether early viral kinetics or other markers during a modified treatment regimen are predictors of treatment outcome and (ii) whether fast responders can be treated for 24 weeks, without compromising the sustained virologic response (SVR) rate. Material and methods. One hundred "difficult-to-treat'' chronic hepatitis C patients (46 previous non-responders/relapsers (any genotype), 54 treatment-naive patients genotypes 1 and 4) were treated with triple antiviral induction therapy: amantadine hydrochloride and ribavirin, combined with 6 weeks interferon alfa-2b induction (weeks 1-2: 18 MU/day, weeks 3-4: 9 MU/day, weeks 5-6: 6 MU/day), thereafter combined with weekly peginterferon alfa-2b. Fast responders (>= 3 log(10) HCV RNA decline at week 4) were randomized to 24 or 48 weeks. Slow responders (= or = 5 IU/mL at week 16 became non-SVR. In previous non-responders/relapsers, the predictive value for SVR was 83% if HCV RNA was = 5 IU/mL at week 8 became non-SVR. Conclusions. With high-dose interferon induction, SVR and non-SVR can be predicted reliably within 16 weeks. Fast responders can be treated for 24 weeks, and SVR is independent of baseline viral load in fast responders

When to perform urodynamics before mid-urethral sling surgery for female stress urinary incontinence?

INTRODUCTION AND HYPOTHESIS: Development of a model that can predict in which group of women pre-operative urodynamics can be safely omitted. METHODS: Three hundred and eighty-one uncomplicated women who underwent pre-operative urodynamics were evaluated. A multivariate logistic regression model was developed based on medical history and physical examination predicting a high probability group of women with detrusor overactivity or a low (<20 cm H2O) mean urethral closure pressure and, therefore, are likely to benefit from urodynamics. RESULTS: Women are likely to benefit from pre-operative urodynamics if they (1) are 53 years of age or older or (2) have a history of prior incontinence surgery and are at least 29 years of age or (3) have nocturia complaints and are at least 36 years of age. CONCLUSION: If urogynaecologists omitted pre-operative urodynamics in women in the low probability group, in our population, pre-operative urodynamics would be reduced by 29

Імунологічні аспекти діагностики та лікування постгістеректомічного синдрому

В статье представлены данные клинико-иммунологического, вегетологического, психологического статуса 80 женщин, страдающих постгистерэктомическими расстройствами с целью поиска оптимальных подходов к терапии. Установлено, что постгистерэктомический синдром сопровождается различными изменениями нейровегетативной регуляции, коррелирующими с гормонально-иммунологическими нарушениями. Стабильные положительные клинико-иммунологические сдвиги у пациенток с постгистерэктомическим синдромом показали высокую эффективность включения иммунокорригирующих препаратов для оптимизации терапевтических мероприятий в борьбе с указанной патологией.Basing on clinical, immunological, vegetologycal investigations in 80 women with posthysterectomy disorders with the purpose of search of optimum pathogenetic approaches to therapy. It has been found that a posthysterectomy syndrome is accompanied by the different changes neyrovegetatic regulationand also psychoemotional disorders. New important hormonal and immunological aspects of pathogenesis were determinated. Stable positive clinical and immunological changes at patients with a postgysterektomy syndrome showed high effect of including of immunological correction for the complex of treatment of patients with this pathology

Clinical statistical analysis plan for the ACCURE trial:the effect of appendectomy on the clinical course of ulcerative colitis, a randomised international multicentre trial

Background: The primary treatment of ulcerative colitis (UC) is medical therapy using a standard step-up approach. An appendectomy might modulate the clinical course of UC, decreasing the incidence of relapses and reducing need for medication. The objective of the ACCURE trial is to assess the efficacy of laparoscopic appendectomy in addition to standard medical treatment in maintaining remission in UC patients. This article presents the statistical analysis plan to evaluate the outcomes of the ACCURE trial. Design and methods: The ACCURE trial was designed as a multicentre, randomised controlled trial. UC patients with a new diagnosis or a disease relapse within the past 12 months, treated with 5-ASA, corticosteroids, or immunomodulators until complete clinical and endoscopic remission (defined as total Mayo score &lt; 3 with endoscopic subscore of 0 or 1), were counselled for inclusion. Also, patients previously treated with biologicals who had a washout period of at least 3 months were considered for inclusion. Patients were randomised (1:1) to laparoscopic appendectomy plus maintenance treatment or a control group (maintenance therapy only). The primary outcome is the 1-year UC relapse rate (defined as a total Mayo-score ≥ 5 with endoscopic subscore of 2 or 3, or clinically as an exacerbation of symptoms and rectal bleeding or FCP &gt; 150 or intensified medical therapy other than 5-ASA therapy). Secondary outcomes include number of relapses per patient, time to first relapse, disease activity, number of colectomies, medication usage, and health-related quality of life. Discussion: The ACCURE trial will provide comprehensive evidence whether adding an appendectomy to maintenance treatment is superior to maintenance treatment only in maintaining remission in UC patients. Trial registration: Dutch Trial Register (NTR) NTR2883. Registered May 3, 2011. ISRCTN, ISRCTN60945764. Registered August 12, 2019

Состояние сексуального здоровья супругов после хирургического вмешательства на внутренних гениталиях женщин

Установлены влияние разных видов операции на сексуальную функцию женщин, причины развития и клинические формы дезадаптации супружеской пары. Сделано заключение о необходимости учитывать при психотерапевтической коррекции дезадаптации помимо объема операции психологические и социально-психологические факторы, способствующие формированию дезадаптации супругов, а в ряде случаев являющиеся ее причиной.The influence of various types of surgery on sexual function of women as well as the causes of development and clinical forms of spouse deadaptation were established. The author concludes about the necessity to consider mental and social-psychological factors contributing formation of spouse deadaptation and its cause in a number of cases in addition to the volume of the surgery at psychotherapeutic correction of deadaptation

Refining the criteria for immediate total-body CT after severe trauma

Objectives Initial trauma care could potentially be improved when conventional imaging and selective CT scanning is omitted and replaced by immediate total-body CT (iTBCT) scanning. Because of the potentially increased radiation exposure by this diagnostic approach, proper selection of the severely injured patients is mandatory. Methods In the REACT-2 trial, severe trauma patients were randomized to iTBCT or conventional imaging and selective CT based on predefined criteria regarding compromised vital parameters, clinical suspicion of severe injuries, or high-risk trauma mechanisms in five trauma centers. By logistic regression analysis with backward selection on the 15 study inclusion criteria, a revised set of criteria was derived and subsequently tested for prediction of severe injury and shifts in radiation exposure. Results In total, 1083 patients were enrolled with median ISS of 20 (IQR 9-29) and median GCS of 13 (IQR 3-15). Backward logistic regression resulted in a revised set consisting of nine original and one adjusted criteria. Positive predictive value improved from 76% (95% CI 74-79%) to 82% (95% CI 80-85%). Sensitivity decreased by 9% (95% CI 7-11%). The area under the receiver operating characteristics curve remained equal and was 0.80 (95% CI 0.77-0.83), original set 0.80 (95% CI 0.77-0.83). The revised set retains 8.78 mSv (95% CI 6.01-11.56) for 36% of the non-severely injured patients. Conclusions Selection criteria for iTBCT can be reduced from 15 to 10 clinically criteria. This improves the positive predictive value for severe injury and reduces radiation exposure for less severely injured patients

Imaging strategies for detection of urgent conditions in patients with acute abdominal pain: diagnostic accuracy study

Objective To identify an optimal imaging strategy for the accurate detection of urgent conditions in patients with acute abdominal pain

Perspectives by patients and physicians on outcomes of mid-urethral sling surgery

Introduction and hypothesis: The aim of this study is to determine patient expectations regarding wanted and unwanted sequels of mid-urethral sling (MUS) procedures and to identify mismatches during the physician-patient information exchange prior to MUS procedures. Methods: A patient preference study (40 patients) and a questionnaire study with 20 experts as control group were conducted. Seventeen different sequels, defined by an expert team, were evaluated. Results: Both patients and expert physicians ranked cure and improvement of stress urinary incontinence as the most important goals of treatment. De novo urge urinary incontinence, requiring post-operative intermittent self-catheterisation and dyspareunia were considered to be the most important complications by patients. Time to resume work after the operation and dyspareunia were among the highest rated sequels in the patient group compared to re-operation and intra-operative complications in the expert group. Conclusions: No differences were found in the five most important outcome parameters. In pre-operative counselling and future clinical trials, time to resume work and dyspareunia should be given more consideration by clinicians

Comparing the Efficacy of Bevacizumab and Ranibizumab in Patients with Diabetic Macular Edema (BRDME):The BRDME Study, a Randomized Trial

Purpose: To generate conclusive evidence regarding the noninferiority of intravitreal bevacizumab compared with ranibizumab in patients with diabetic macular edema (DME). Design: Comparative, randomized, double-masked, multicenter, noninferiority clinical trial. Participants: Eligible patients were older than 18 years, diagnosed with type 1 or type 2 diabetes mellitus, with glycosylated hemoglobin of less than 12%, central area thickness of more than 325 μm, and visual impairment from DME with a best-corrected visual acuity (BCVA) between 24 letters and 78 letters. Methods: From June 2012 through February 2018, a total of 170 participants were randomized to receive 6 monthly injections of either 1.25 mg bevacizumab (n = 86) or 0.5 mg ranibizumab (n = 84). Main Outcome Measures: Primary outcome was change in BCVA from baseline to month 6 compared between the 2 treatment arms. The noninferiority margin was 3.5 letters. Results: The difference in mean BCVA between treatment arms was 1.8 letters in favor of ranibizumab after 6 months of follow-up; BCVA improved by 4.9±6.7 letters in the bevacizumab group and 6.7±8.7 letters in the ranibizumab group. The lower bound of the 2-sided 90% confidence interval (CI) was –3.626 letters, exceeding the noninferiority margin of 3.5 letters. Central area thickness decreased more with ranibizumab (138.2±114.3 μm) compared with bevacizumab (64.2±104.2 μm). In a post hoc subgroup analysis, participants with a worse BCVA at baseline (≤69 letters) improved by 6.7±7.0 letters with bevacizumab and 10.4±10.0 letters with ranibizumab, and central area thickness decreased significantly more in the ranibizumab arm of this subgroup compared with the bevacizumab arm. Participants with an initially better BCVA at baseline (≥70 letters) did not demonstrate differences in BCVA or OCT outcomes between treatment arms. Conclusions: Based on change in BCVA from baseline to month 6, the noninferiority of 1.25 mg bevacizumab to 0.5 mg ranibizumab was not confirmed. Only the subgroup of patients with a lower BCVA at baseline showed better visual acuity and anatomic outcomes with ranibizumab. Our study confirmed the potential differential efficacy of anti–vascular endothelial growth factor agents in the treatment of DME as well as the difference in response between patient groups with different baseline visual acuities

Quantified health and cost effects of faster endovascular treatment for large vessel ischemic stroke patients in the Netherlands

BACKGROUND: The effectiveness of endovascular treatment (EVT) for large vessel occlusion (LVO) stroke severely depends on time to treatment. However, it remains unclear what the value of faster treatment is in the years after index stroke. The aim of this study was to quantify the value of faster EVT in terms of health and healthcare costs for the Dutch LVO stroke population. METHODS: A Markov model was used to simulate 5-year follow-up functional outcome, measured with the modified Rankin Scale (mRS), of 69-year-old LVO patients. Post-treatment mRS was extracted from the MR CLEAN Registry (n=2892): costs per unit of time and Quality-Adjusted Life Years (QALYs) per mRS sub-score were retrieved from follow-up data of the MR CLEAN trial (n=500). Net Monetary Benefit (NMB) at a willingness to pay of €80 000 per QALY was reported as primary outcome, and secondary outcome measures were days of disability-free life gained and costs. RESULTS: EVT administered 1 min faster resulted in a median NMB of €309 (IQR: 226;389), 1.3 days of additional disability-free life (IQR: 1.0;1.6), while cumulative costs remained largely unchanged (median: -€15, IQR: -65;33) over a 5-year follow-up period. As costs over the follow-up period remained stable while QALYs decreased with longer time to treatment, which this results in a near-linear decrease of NMB. Since patients with faster EVT lived longer, they incurred more healthcare costs. CONCLUSION: One-minute faster EVT increases QALYs while cumulative costs remain largely unaffected. Therefore, faster EVT provides better value of care at no extra healthcare costs