Self-expandable metal stents (SEMS) are used to relieve malignant luminal obstruction throughout the gastrointestinal tract. Colonic SEMS are used most often for palliation of obstruction in ...nonoperative candidates or in patients with advanced disease. The other indication for colonic stent placement is as a preoperative modality for the relief of acute obstruction so that resection can be done on an elective basis after stabilization of the acute illness and bowel preparation. For both of these indications, the goal is avoidance of a temporary or permanent ostomy. In this manuscript the supporting data for each of these indications will be reviewed.
Despite poor prognosis, patients with type 2 myocardial infarction (MI) tend to be underdiagnosed and undertreated compared to those with type 1 MI. Whether this discrepancy has improved over time is ...uncertain. We conducted a registry-based cohort study investigating type 2 MI patients managed at Swedish coronary care units (n = 14,833) during 2010-2022. Multivariable-adjusted changes (first three vs last three calendar years of the observation period) were assessed regarding diagnostic examinations (echocardiography, coronary assessment), provision of cardioprotective medications (betablockers, renin-angiotensin-aldosterone-system inhibitors, statins) and 1-year all-cause mortality. Compared to type 1 MI patients (n = 184,329), those with type 2 MI less often had diagnostic examinations and cardioprotective medications. Increases in the use of echocardiography (OR 1.08 95% confidence interval 1.06-1.09) and coronary assessment (OR 1.06 95% confidence interval 1.04-1.08) were smaller compared to type 1 MI (p
< 0.001). The provision of medications did not increase in type 2 MI. All-cause mortality rate in type 2 MI was 25.4% without temporal change (OR 1.03 95% confidence interval 0.98-1.07). Taken together, the provision of medications and all-cause mortality did ot improve in type 2 MI despite modest increases in diagnostic procedures. This emphasizes the need of defining optimal care pathways in these patients.
Prostate cancer is a major cause of cancer-related death in American men, for which finding new therapeutic strategies remains a challenge. Early growth response-1 (EGR1) is a transcription factor ...involved in cell proliferation and in the regulation of apoptosis. Although it has long been considered a tumor suppressor, a wealth of new evidence shows that EGR1 promotes the progression of prostate cancer. This review addresses the paradoxes of EGR1 function. While EGR1 mediates apoptosis in response to stress and DNA damage by regulating a tumor suppressor network, it also promotes the proliferation of prostate cancer cells by a mechanism that is not fully understood. Thus, EGR1 might be targeted for prostate cancer therapy either by ectopic expression in combination with radiotherapy or chemotherapy, or by direct inhibition for systemic treatment. Possible strategies to antagonize EGR1 function in a therapeutic setting are discussed.
Patients with hearing loss and tinnitus face lengthy waits to be seen in the ENT clinic. SHOEBOX Audiometry is an iPad-based, audiometric screening tool. A virtual hearing loss and non-pulsatile ...tinnitus clinic involving an ENT specialist virtually assessing cases based on the SHOEBOX audiogram, a patient symptom questionnaire and the primary care referral letter were implemented. This service evaluation explored the outcomes of the virtual clinic in reducing the need for a face-to-face ENT appointment.
This was a retrospective service evaluation of the first six months of the virtual hearing loss and non-pulsatile tinnitus clinic.
A total of 210 patients were included: 34.8 per cent (73) were discharged without requiring audiologist assessment or an ENT appointment, 51.9 per cent (109) required formal audiological assessment, 36.7 per cent (77) required imaging and only 13.8 per cent (29) required a face-to-face ENT appointment.
A virtual hearing loss and non-pulsatile tinnitus clinic minimised the number of patients requiring a traditional face-to-face clinic appointment within ENT.
Plumbagin is a candidate drug for the treatment of prostate cancer. Previous observations indicated that it may improve the efficacy of androgen deprivation therapy (ADT). This study evaluates the ...effectiveness of treatment with combinations of plumbagin and alternative strategies for ADT in mouse models of prostate cancer to support its clinical use.
Plumbagin was administered per oral in a new sesame oil formulation. Standard toxicology studies were performed in rats. For tumor growth studies, mouse prostate cancer cell spheroids were placed on top of grafted prostate tissue in a dorsal chamber and allowed to form tumors. Mice were separated in various treatment groups and tumor size was measured over time by intra-vital microscopy. Survival studies were done in mice after injection of prostate cancer cells in the prostate of male animals. Androgen receptor (AR) levels were analyzed by Western blot from prostate cancer cells treated with plumbagin.
Plumbagin caused a decrease in AR levels in vitro. In mice, plumbagin at 1 mg/kg in sesame oil displayed low toxicity and caused a 50% tumor regression when combined with castration. The combination of plumbagin with various forms of chemical ADT including treatment with a GnRH receptor agonist, a GnRH receptor antagonist, or CYP17A1 inhibitors, outperformed ADT alone, increasing mouse survival compared to the standard regimen of castration alone. In contrast, the combination of plumbagin with AR antagonists, such as bicalutamide and enzalutamide, showed no improvement over AR antagonists alone. Thus, plumbagin is effective in combination with drugs that prevent the synthesis of testosterone or its conversion to dihydrotestosterone, but not with drugs that bind to AR.
Plumbagin significantly improves the effect of ADT drugs currently used in the clinic, with few side effects in mice.
Myocardial infarction (MI) with non-obstructive coronary arteries (MINOCAs) is an increasingly recognized entity. No previous study has evaluated predictors for new major adverse cardiacvascular ...events (MACEs) and death in patients with MINOCA.
We conducted an observational study of MINOCA patients recorded between July 2003 and June 2013 and followed until December 2013 for outcome events. Out of 199,163 MI admissions, 9092 consecutive unique patients with MINOCA were identified. The mean age was 65.5 years and 62% were women. MACE was defined as all-cause mortality, rehospitalization for acute MI, ischemic stroke and heart failure. Hazard ratio and 95% confidence interval (HR; 95% CI) was calculated using Cox-regression.
A total of 2147 patients (24%) experienced a new MACE and 1254 patients (14%) died during the mean follow-up of 4.5 years. Independent predictors for MACE after adjustment, were older age (1.05; 1.04–1.06), diabetes (1.44; 1.21–1.70), hypertension (1.25; 1.09–1.43), current smoking (1.38; 1.15–1.66), previous myocardial infarction (1.38; 1.04–2.82), previous stroke (1.69; 1.35–2.11), peripheral vascular disease (1.55; 1.97–2.23), chronic obstructive pulmonary disease (1.63; 1.32–2.00), reduced left ventricular ejection fraction (2.00; 1.54–2.60), lower level of total cholesterol (0.88; 0.83–0.94) and higher level of creatinine (1.01; 1.00–1.03). Independent predictors for all cause death were age, current smoking, diabetes, cancer, chronic obstructive pulmonary disease, previous stroke, reduced left ventricular fraction, lower level of total cholesterol and higher levels of creatinine and CRP.
The clinical factors predicting new MACE and death of MINOCA patients seem to be strikingly similar to factors previously shown to predict new cardiovascular events in patients with MI and obstructive coronary artery disease.
•Myocardial infarction with non-obstructive coronary arteries (MINOCAs) is common.•One quarter of MINOCA patients experience a new MACE during follow-up.•Predictors of new MACE are similar to previously known risk factors for CAD.
Endoscopic retrograde cholangiopancreatography (ERCP) is challenging to perform in patients with postsurgical gastrointestinal anatomy. We assessed the diagnostic and therapeutic success rates using ...single-balloon enteroscopy in patients with Roux-en-Y anastomosis.
Patients who underwent single-balloon ERCP between April 2008 and February 2010 were retrospectively identified using a computerized endoscopy database. Diagnostic success was defined as successful duct cannulation or securing the diagnosis, and therapeutic success was defined as the ability to successfully carry out endoscopic therapy. Complications of ERCP were defined according to standard criteria.
A total of 50 patients (34-male, mean age 57 years, range 19 - 85 years) with Roux-en-Y anastomosis underwent ERCP using a single-balloon enteroscope on 56 occasions. Indications for ERCP were cholestasis, acute cholangitis, recurrent primary sclerosing cholangitis with strictures, and choledocholithiasis. Overall diagnostic success was achieved in 39 / 56 cases (70 %). Therapeutic success was achieved in 21/23 cases (91 %). In 16 cases therapeutic intervention was not required. Therapeutic interventions included balloon dilation of strictures (n = 14), retrieval of retained biliopancreatic stents (n = 5), biliary stone extraction (n = 2), insertion of biliopancreatic stents (n = 4), and biliary and pancreatic sphincterotomy (n = 5). No major complications occurred. Importantly, in 22 / 56 procedures (39 %) a prior attempt at ERCP failed using conventional colonoscopes; single-balloon ERCP was successful in 15 / 22 (68 %) of these cases.
Single-balloon ERCP is feasible in patients with complex postsurgical Roux-en-Y anastomosis, allows diagnostic evaluation and therapeutic intervention in patients with pancreaticobiliary disease, and is a useful salvage technique in the majority of patients in whom ERCP using colonoscopies has failed.
mrgsolve is an open‐source R package available on the Comprehensive R Archive Network. It combines R and C++ coding for simulation from hierarchical, ordinary differential equation–based models. Its ...efficient simulation engine and integration into a parallelizable, R‐based workflow makes mrgsolve a convenient tool both for simple and complex models and thus is ideal for physiologically‐based pharmacokinetic (PBPK) and quantitative systems pharmacology (QSP) model. This tutorial will first introduce the basics of the mrgsolve simulation workflow, including model specification, the introduction of interventions (dosing events) into the simulation, and simulated results postprocessing. An applied simulation example is then presented using a PBPK model for voriconazole, including a model validation step against adult and pediatric data sets. A final simulation example is then presented using a previously published QSP model for mitogen‐activated protein kinase signaling in colorectal cancer, illustrating population simulation of different combination therapies.
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