Clinical relevance of thymidylate syntetase expression in the signet ring cell histotype component of colorectal carcinoma

Thymidylate Synthase (TS) is the key enzyme for DNA synthesis pathways and is inhibited by 5-fluorouracil (5FU). The aim of this work was to study TS expression and the proliferation rate in the different histological types of colorectal carcinoma (CRC). 50 patients with CRC were included in this study and evaluated immunohistochemically using the monoclonal antibodies, TS106 and Ki67. 20 tumours were of the intestinal type, 15 cases were signet ring cell carcinoma (SRCCs) and 15 cases were "mixed-type", with at least two different histological components. Intestinal and mucinous histotypes were positive for TS and Ki67, while "signet ring cell" samples were negative or showed only weak and focal positivity for both the TS and Ki67 antibodies. Our results show that signet ring cells (that are also often present in intestinal and mucinous carcinomas), are in the post-mitotic phase of the cell cycle and show a low proliferation index and TS expression. As TS is the key enzyme for DNA synthesis pathways and is inhibited by 5-fluorouracil (5FU), we can hypothesise that TS expression levels in the different histotypes of CRC could affect the potential responsiveness of these tumours to fluoropyrimidine chemotherapy, with a low efficacy being expected in signet ring cell areas

Kinematic algorithm to determine the energy cost of running with changes of direction

Changes of direction (CoDs) have a high metabolic and mechanical impact in field and court team sports, but the estimation of the associated workload is still inaccurate. This study aims at validating an algorithm based on kinematic data to estimate the energy cost of running with frequent 180\ub0-CoDs. Twenty-six physically active male subjects (22.4\u202f\ub1\u202f3.2\u202fyears) participated in two sessions: (1) maximum oxygen uptake (V\u307O2,max) and maximal aerobic speed (MAS) test; (2) 5-m continuous shuttle run (two 5-min trials at 50% and 75% MAS, 6-min recovery). In (2), full-body 3D-kinematics and V\u307O2 were simultaneously recorded. Actual cost of shuttle running (Cmeas) was obtained from the aerobic, anaerobic alactic and lactic components. The proposed algorithm detects "braking phases", periods of mostly negative (eccentric) work occurring at concurrent knee flexion and ground contact, and estimates energy cost (Cest) considering negative mechanical work in braking phases, and positive elsewhere. At the speed of, respectively, 1.54\u202f\ub1\u202f0.17 and 1.90\u202f\ub1\u202f0.15\u202fm\u202fs-1 (rate of perceived exertion: 9.1\u202f\ub1\u202f1.8 and 15.8\u202f\ub1\u202f1.9), Cmeas was 8.06\u202f\ub1\u202f0.49 and 9.04\u202f\ub1\u202f0.73\u202fJ\u202fkg-1\u202fm-1. Cest was more accurate than regression models found in literature (p\u202f\u202f0.05; average error: 8.3%, root-mean-square error: 0.86\u202fJ\u202fkg-1\u202fm-1). The proposed algorithm improved existing techniques based on CoM kinematics, integrating data of ground contacts and joint angles that allowed to separate propulsive from braking phases. This work constitutes the basis to extend the model from the laboratory to the field, providing a reliable measure of training and matches workload

Clinical and Experimental Projects on Chemotherapy of Bladder Tumours

Our clinical and experimental experience with chemotherapy of bladder tumours is reviewed. The routes of drug administrations, drug dosages and combinations, are presented. Adjuvant radiotherapy and chemoprophylaxis of certain tumours are discussed.S. Afr. Med. J., 48, 631 (1974

Clinical and experimental projects on chemotherapy of bladder tumours

Click on the link to view

Thoracoscopic removal of dental prosthesis impacted in the upper thoracic esophagus

Dental appliances are the most common cause of accidental foreign body esophageal impaction, especially in the elderly population with decreased oral sensory perception. A 47-year-old man with history of oligophrenia and recurrent epileptic seizures was referred to our hospital following dislocation and ingestion of his upper dental prosthesis. Endoscopic removal and clipping of an esophageal tear had been unsuccessfully attempted. A chest CT scan confirmed entrapment of the dental prosthesis in the upper thoracic esophagus, the presence of pneumomediastinum, and the close proximity of one of the metal clasps of the prosthesis to the left subclavian artery. A video-assisted right thoracoscopy in the left lateral decubitus position was performed and the foreign body was successfully removed. The patient was then allowed to wear the retrieved prosthesis after dentistry consultation and repair of the wire clasps by a dental technician. At the 6-month follow-up visit the patient was doing very well without any trouble in swallowin

Effect of powered circular stapler in colorectal anastomosis after left-sided colic resection: systematic review and meta-analysis

Purpose: Anastomotic leak (AL) remains the most important complication after left-sided colic anastomoses and technical complications during anastomotic construction are responsible of higher leakage incidence. Powered circular stapler (PCS) in colorectal surgery has been introduced in order to reduce technical errors and post-operative complications due to the manual circular stapler (MCS). Methods: A systematic review and meta-analysis were performed. An electronic systematic search was performed using Web of Science, PubMed, and Embase of studies comparing PCS and MCS. The incidence of AL, anastomotic bleeding (AB), conversion, and reoperation were assessed. PROSPERO Registration Number: CRD42024512644. Results: Five observational studies were eligible for inclusion reporting on 2379 patients. The estimated pooled Risk Ratios for AL and AB rates following PCS were significantly lower than those observed with MCS (0.44 and 0.23, respectively; both with p < 0.01). Conversion and reoperation rate did not show any significant difference: 0.41 (95% CI 0.09–1.88; p = 0.25) and 0.78 (95% CI 0.33–1.84; p = 0.57); respectively. Conclusion: The use of PCS demonstrates a lower incidence of AL and AB compared to MCS but does not exhibit a discernible influence on reintervention or conversion rates. The call for future randomized clinical trials aims to definitively clarify these issues and contribute to further advancements in refining surgical strategies for left-sided colonic resection

Laparoscopy in management of appendicitis in high-, middle-, and low-income countries: a multicenter, prospective, cohort study.

BACKGROUND: Appendicitis is the most common abdominal surgical emergency worldwide. Differences between high- and low-income settings in the availability of laparoscopic appendectomy, alternative management choices, and outcomes are poorly described. The aim was to identify variation in surgical management and outcomes of appendicitis within low-, middle-, and high-Human Development Index (HDI) countries worldwide. METHODS: This is a multicenter, international prospective cohort study. Consecutive sampling of patients undergoing emergency appendectomy over 6 months was conducted. Follow-up lasted 30 days. RESULTS: 4546 patients from 52 countries underwent appendectomy (2499 high-, 1540 middle-, and 507 low-HDI groups). Surgical site infection (SSI) rates were higher in low-HDI (OR 2.57, 95% CI 1.33-4.99, p = 0.005) but not middle-HDI countries (OR 1.38, 95% CI 0.76-2.52, p = 0.291), compared with high-HDI countries after adjustment. A laparoscopic approach was common in high-HDI countries (1693/2499, 67.7%), but infrequent in low-HDI (41/507, 8.1%) and middle-HDI (132/1540, 8.6%) groups. After accounting for case-mix, laparoscopy was still associated with fewer overall complications (OR 0.55, 95% CI 0.42-0.71, p < 0.001) and SSIs (OR 0.22, 95% CI 0.14-0.33, p < 0.001). In propensity-score matched groups within low-/middle-HDI countries, laparoscopy was still associated with fewer overall complications (OR 0.23 95% CI 0.11-0.44) and SSI (OR 0.21 95% CI 0.09-0.45). CONCLUSION: A laparoscopic approach is associated with better outcomes and availability appears to differ by country HDI. Despite the profound clinical, operational, and financial barriers to its widespread introduction, laparoscopy could significantly improve outcomes for patients in low-resource environments. TRIAL REGISTRATION: NCT02179112

Dor versus Toupet fundoplication after Laparoscopic Heller Myotomy: Systematic review and Bayesian meta-analysis of randomized controlled trials

Laparoscopic Heller Myotomy (LHM) with partial fundoplication has become the treatment of choice for esophageal achalasia. However, the choice of the partial fundoplication is debated. The aim of this study was to compare outcomes for Dor and Toupet fundoplication after LHM. A systematic search of randomized controlled trials comparing Dor and Toupet fundoplication was performed using PubMed, EMBASE and Web of Science. Three studies met the inclusion criteria. Overall, 174 patients were included in the analysis. The postoperative abnormal acid reflux [pooled Risk Ratio 0.98 (95% HPD 0.54-1.80)] and dysphagia [pooled Risk Ratio 1.03 (95% HPD 0.51-2.05)] were similar comparing Dor and Toupet fundoplication. The % total time pH&nbsp; 64&nbsp;4 [estimated pooled mean difference -0.08 (95% HPD -1.04-0.90)] and DeMeester score [estimated pooled mean difference 0.51 (95% HPD -0.90-1.94)] were comparable. Additionally, the operative time [estimated pooled mean difference 0.02 (95% HPD -0.53-0.52)] and iatrogenic esophageal perforation [pooled Risk Ratio 1.05 (95% HPD 0.52-2.10)] were similar in the two groups. Dor and Toupet fundoplication after laparoscopic Heller myotomy seem comparable in term of postoperative abnormal acid exposure and dysphagia. The choice of the partial fundoplication should be left to surgeon experience and tailored on each patient

Deep Learning-Based Psoriasis Assessment: Harnessing Clinical Trial Imaging for Accurate Psoriasis Area Severity Index Prediction

Introduction: Image-based machine learning holds great promise for facilitating clinical care; however, the datasets often used for model training differ from the interventional clinical trial-based findings frequently used to inform treatment guidelines. Here, we draw on longitudinal imaging of psoriasis patients undergoing treatment in the Ultima 2 clinical trial (NCT02684357), including 2,700 body images with psoriasis area severity index (PASI) annotations by uniformly trained dermatologists. Methods: An image-processing workflow integrating clinical photos of multiple body regions into one model pipeline was developed, which we refer to as the “One-Step PASI” framework due to its simultaneous body detection, lesion detection, and lesion severity classification. Group-stratified cross-validation was performed with 145 deep convolutional neural network models combined in an ensemble learning architecture. Results: The highest-performing model demonstrated a mean absolute error of 3.3, Lin’s concordance correlation coefficient of 0.86, and Pearson correlation coefficient of 0.90 across a wide range of PASI scores comprising disease classifications of clear skin, mild, and moderate-to-severe disease. Within-person, time-series analysis of model performance demonstrated that PASI predictions closely tracked the trajectory of physician scores from severe to clear skin without systematically over- or underestimating PASI scores or percent changes from baseline. Conclusion: This study demonstrates the potential of image processing and deep learning to translate otherwise inaccessible clinical trial data into accurate, extensible machine learning models to assess therapeutic efficacy

GREENPEG exploration for pegmatite minerals to feed the energy transition: first steps towards the Green Stone Age

The GREENPEG project, which is funded by the European Commission Horizon 2020 Climate action, environment, resource efficiency and raw materials programme, aims to develop multimethod exploration toolsets for the identification of European, buried, small-scale (0.015 million m3 ) pegmatite ore deposits of the NbYF (NYF) and LiCsTa (LCT) chemical types. The project is being coordinated by the Natural History Museum of the University of Oslo and involves four exploration services/mining operators, one geological survey, one non-profit helix association of administration, industry and academia, two consulting companies and five academic institutions from eight European countries. The target raw materials are Li, high-purity quartz for silica and metallic Si, ceramic feldspar, rare earth elements, Ta, Be and Cs, which are naturally concentrated in granitic pegmatites. Silicon and Li are two of the most sought-after green technology metals as they are essential for photovoltaics and Li-ion batteries for electric cars, respectively. GREENPEG will change the focus of exploration strategies from large-volume towards small-volume, high-quality ores and overcome the lack of exploration technologies for pegmatite ore deposits by developing toolsets tailored to these ore types. This contribution focuses on the methods applied in the GREENPEG project and as such provides a potential pathway towards the Green Stone Age from the perspective of pegmatite-sourced minerals. (c) 2022 The Author(s)