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Background: Pneumatosis intestinalis (PI) is a rare entity which refers to the presence of gas within the wall of the small bowel or colon which is a radiographic sign. The etiology and clinical presentation are variable. Patients with PI may present either with chronic mild non-specific symptoms or with acute abdominal pain with peritonitis. Some cases of intestinal pneumatosis have been reported as adverse events of new oncological treatments such as targeted therapies that are widely used in multiple tumors.Case Presentation: A 59-year-old caucasian female with radioactive iodine-refractory metastatic thyroid papillary carcinoma with BRAFV600E mutation was treated with dabrafenib and trametinib as a compassionate use. After 4 months treatment, positron emission tomography-computed tomography (PET-CT) showed PI. At the time of diagnosis, the patient was asymptomatic without signs of peritonitis. The initial treatment was conservative and no specific treatment for PI was needed. Unfortunately, after dabrafenib-trametinib withdrawal, the patient developed tumor progression with significant clinical worsening.Conclusions: This case report is, in our knowledge, the first description of PI in a patient treated with dabrafenib-trametinib. Conservative treatment is feasible if there are no abdominal symptoms. [ABSTRACT FROM AUTHOR]

A rational use of production resources has been catalysing the attention of researchers and practitioners for several years. A number of indicators have been proposed to assess the effective and efficient use of the various production factors. A widely known example of these metrics is the overall equipment effectiveness (OEE), which applies to machines and equipment. This paper proposes a novel methodology that seizes upon OEE’s straight forward and easy-to-use structure to address the problem of measuring the effective use of materials within a factory. An inclusive structure of material loss and a methodology to calculate a novel performance indicator called overall material usage effectiveness (OME) is given. The proposed set of KPIs not only permits the comprehension of material-related issues but also the identification of viable countermeasures. A real-life application to demonstrate the practical usefulness of the methodology and illustrate the capability of its KPIs is described. [ABSTRACT FROM PUBLISHER]

Aim Very few studies have compared the epidemiological characteristics of patients with familial colorectal cancer Type X ( FCCTX) with those of sporadic colorectal cancer (S- CRC). The aim of this study was to compare clinicopathological characteristics and survival between FCCTX and S- CRC in patients from a historically isolated geographical region. Method A retrospective study was carried out of patients with S- CRC and FCCTX treated in the Canary Islands. Family and personal history of colorectal cancer ( CRC) were recorded, together with genetic (microsatellite instability), immunohistochemical and clinical variables. Results Forty-eight (10.6%) of 451 patients were classified as FCCTX and the remaining 403 (89.4%) as S- CRC. Age at the diagnosis of tumour was significantly lower in FCCTX than in S- CRC (64.06 ± 12.65 years vs 69.13 ± 10.80 years; P = 0.01; Z = −2.48). Patients with FCCTX had a larger number of synchronous tumours ( P = 0.09). Recurrence was significantly higher in FCCTX than in S- CRC (18.7% vs 8.6%; P = 0.01). Survival correlated significantly with the number of first-degree and second-degree relatives with CRC ( P = 0.04; OR: 1.368, 95% CI: 1.01-1.84, and P = 0.04; OR: 1.363, 95% CI: 1.08-1.65) and with the total number of cases of CRC in the immediate family ( P < 0.01; OR: 1.377, 95% CI: 1.17-1.61). Recurrence-free time was significantly lower in patients with FCCTX (log-rank = 0.01). Conclusion Significant differences were found in several demographic and clinicopathological variables between patients with FCCTX and patients with S- CRC. These included increased tumour presentation under the age of 50 years and a higher recurrence rate in patients with FCCTX, suggesting an increased risk of CRC in this group. [ABSTRACT FROM AUTHOR]

Background:We report final results with extended follow-up from a global, expanded-access trial that pre-regulatory approval provided sunitinib to metastatic renal cell carcinoma (mRCC) patients, ineligible for registration-directed trials.Methods:Patients ⩾18 years received oral sunitinib 50 mg per day on a 4-weeks-on-2-weeks-off schedule. Safety was assessed regularly. Tumour measurements were scheduled per local practice.Results:A total of 4543 patients received sunitinib. Median treatment duration and follow-up were 7.5 and 13.6 months. Objective response rate was 16% (95% confidence interval (CI): 15-17). Median progression-free survival (PFS) and overall survival (OS) were 9.4 months (95% CI: 8.8-10.0) and 18.7 months (95% CI: 17.5-19.5). Median PFS in subgroups of interest: aged ⩾65 years (33%), 10.1 months; Eastern Cooperative Oncology Group performance status ⩾2 (14%), 3.5 months; non-clear cell histology (12%), 6.0 months; and brain metastases (7%), 5.3 months. OS was strongly associated with the International Metastatic Renal-Cell Carcinoma Database Consortium prognostic model (n=4065). The most common grade 3/4 treatment-related adverse events were thrombocytopenia (10%), fatigue (9%), and asthenia, neutropenia, and hand-foot syndrome (each 7%).Conclusion:Final analysis of the sunitinib expanded-access trial provided a good opportunity to evaluate the long-term side effects of a tyrosine kinase inhibitor used worldwide in mRCC. Efficacy and safety findings were consistent with previous results. [ABSTRACT FROM AUTHOR]

Pook se Bos informal settlement and the Cape Town Water & Sanitation Services Department are partnering on an urban sanitation project with a Dutch Consortium consisting of Lettinga Associates Foundation (LeAF), Landustrie Sneek and Vitens-Evides International. The aim of the project is to improve the basic sanitation services provided in informal settlements through the implementation of the MobiSan approach. The approach consists of a communal Urine-Diversion and Dehydration Toilet (UDDT) built in a former sea shipping container. The system is independent of water, electricity or sewerage connection and it is maintained by full-time community caretakers who also act as hygiene promoters. The project seeks to link sanitation services with hygiene promotion in informal settlements while enhancing user satisfaction and reducing costs in providing basic sanitation services. This paper describes the preliminary experiences and lessons learnt during the implementation and evaluation of the MobiSan prototype and discusses its potential for replication. The MobiSan has proved to be an appropriate option by means of dealing successfully with shallow groundwater table, land availability and high settlement densities. In addition it has been demonstrated to be cost-competitive in terms of operating cost compared to chemical toilets. [ABSTRACT FROM AUTHOR]

Abstract: Sanitation coverage in the informal settlements of Cape Town is severely lagging behind. A recent inventory showed that the main barriers to the implementation of proper sanitation systems are unsuitability of the location of many settlements (more than 40% of the sites are located on private land, wetlands and flooding prone areas), high settlement densities (55%), the nonpermanent status of the informal settlements and the distance to existing sewerage networks. The technical feasibility of 14 different sanitation systems was related to these general constraints. The feasibility assessment showed that only chemical toilets and container toilets were systems that could be applied on a larger scale. Both toilet systems, however, have high service and maintenance costs. Based on the evaluation, an innovative pilot project consisting of a mobile sanitation unit (MobiSan1) is being developed and will be piloted. [Copyright &y& Elsevier]

Urothelial bladder cancer (UC) is the most common malignancy involving the urinary system and represents a significant health problem. Immunotherapy has been used for decades for UC with intravesical bacillus Calmette-Guérin (BCG) set as the standard of care for non-muscle-invasive bladder cancer (NMIBC). The advent of immune checkpoint inhibitors (ICIs) has completely transformed the treatment landscape of bladder cancer enabling to expand the treatment strategies. Novel ICIs have successfully shown improved outcomes on metastatic disease to such an extent that the standard of care paradigm has changed leading to the development of different trials with the aim of determining whether ICIs may have a role in early disease. The localized muscle-invasive bladder cancer (MIBC) scenario remains challenging since the recurrence rate continues to be high despite all therapeutic efforts. This article will review the current experience of ICIs in the neoadjuvant setting of UC, the clinical trials landscape and finally, an insight of what to expect in the immediate and mid-term future. [ABSTRACT FROM AUTHOR]

BACKGROUND No treatment has surpassed platinum-based chemotherapy in improving overall survival in patients with previously untreated locally advanced or metastatic urothelial carcinoma. METHODS We conducted a phase 3, global, open-label, randomized trial to compare the efficacy and safety of enfortumab vedotin and pembrolizumab with the efficacy and safety of platinum-based chemotherapy in patients with previously untreated locally advanced or metastatic urothelial carcinoma. Patients were randomly assigned in a 1:1 ratio to receive 3-week cycles of enfortumab vedotin (at a dose of 1.25 mg per kilogram of body weight intravenously on days 1 and 8) and pembrolizumab (at a dose of 200 mg intravenously on day 1) (enfortumab vedotin-pembrolizumab group) or gemcitabine and either cisplatin or carboplatin (determined on the basis of eligibility to receive cisplatin) (chemotherapy group). The primary end points were progression-free survival as assessed by blinded independent central review and overall survival. RESULTS A total of 886 patients underwent randomization: 442 to the enfortumab vedotin- pembrolizumab group and 444 to the chemotherapy group. As of August 8, 2023, the median duration of follow-up for survival was 17.2 months. Progression-free survival was longer in the enfortumab vedotin-pembrolizumab group than in the chemotherapy group (median, 12.5 months vs. 6.3 months; hazard ratio for disease progression or death, 0.45; 95% confidence interval [CI], 0.38 to 0.54; P<0.001), as was overall survival (median, 31.5 months vs. 16.1 months; hazard ratio for death, 0.47; 95% CI, 0.38 to 0.58; P<0.001). The median number of cycles was 12 (range, 1 to 46) in the enfortumab vedotin-pembrolizumab group and 6 (range, 1 to 6) in the chemotherapy group. Treatment-related adverse events of grade 3 or higher occurred in 55.9% of the patients in the enfortumab vedotin-pembrolizumab group and in 69.5% of those in the chemotherapy group. CONCLUSIONS Treatment with enfortumab vedotin and pembrolizumab resulted in significantly better outcomes than chemotherapy in patients with untreated locally advanced or metastatic urothelial carcinoma, with a safety profile consistent with that in previous reports. (Funded by Astellas Pharma US and others; EV-302 ClinicalTrials.gov number, NCT04223856.) [ABSTRACT FROM AUTHOR]