Oral ulcers as a presentation of secondary syphilis

The incidence of syphilis is increasing and typically presents in patients with known risk factors, often to genitourinary physicians. Cases presenting to a dermatologist or ophthalmologist will more likely have secondary syphilis, which is potentially associated with complications. Early recognition is therefore vital to limit both the disease and risk of further contact spread. In this review, we include two case histories demonstrating the value of recognizing oral signs. Additionallym we review the currently accepted diagnostic and therapeutic recommendations

Relugolix Plus Enzalutamide For Metastatic Hormone-Sensitive Prostate Cancer: A Case Report

Alastair Thomson,1 Lucinda Gunn,1 Deborah Victor,1 Ellis Adamson,1 Kashyap Thakrar2 1Oncology Department, Sunrise Centre, Royal Cornwall Hospital, Truro, Cornwall, UK; 2Accord-UK Ltd, Barnstaple, Devon, UKCorrespondence: Alastair Thomson, Oncology department, Sunrise Centre, Royal Cornwall Hospital, Truro, Cornwall, TR1 3LJ, UK, Tel +44 (0)1872 250000, Email [email protected]: In the UK, relugolix, an oral gonadotropin-releasing hormone receptor antagonist, is indicated for advanced hormone-sensitive prostate cancer, and as neo-adjuvant and adjuvant treatment in combination with radiotherapy in patients with high-risk localised or locally advanced hormone-dependent prostate cancer. Experience with the combination of oral relugolix plus oral enzalutamide is limited.Case Presentation: A white British male (66 years old) with a history of myelodysplastic syndrome, chronic neutropenia and indeterminate colitis presented with metastatic adenocarcinoma of the prostate gland. The patient started subcutaneous leuprorelin acetate and oral enzalutamide. After 8 weeks, the oral enzalutamide dose was reduced because of fatigue. Following the second leuprorelin injection, the patient developed a subcutaneous abscess that required surgical incision and drainage. The patient switched to oral relugolix and continued with oral enzalutamide. Within 3 months of commencing leuprorelin and enzalutamide the prostate specific antigen (PSA) concentration fell from a peak of 269.00 ng/mL to 2.55 ng/mL. Following the switch to oral relugolix plus enzalutamide, the PSA remained stable until the most recent assessment 11 months later. Relugolix plus enzalutamide was well tolerated.Conclusion: Relugolix plus enzalutamide produced a sustained reduction in PSA and the combination was well tolerated. Further research including real world data should assess relugolix in doublet and triplet combinations for prostate cancer.Plain Language Summary: Oral (by mouth) relugolix can treat certain men with hormone sensitive prostate cancer. Studies are underway looking at relugolix combined with other drugs, such as oral enzalutamide, and at various stages of prostate cancer. Dr Thomson et al report the case of a man with other serious diseases who took oral relugolix and oral enzalutamide after experiencing side effects with injectable drugs. His levels of prostate specific antigen (PSA), which indicates prostate cancer control (the lower the better), fell markedly after starting treatment and, after switching to relugolix, remained stable for 11 months. He tolerated relugolix plus enzalutamide well.Keywords: relugolix, enzalutamide, prostate cancer, gonadotropin-releasing hormone receptor antagonist, prostate specific antige

Effectiveness and side-effect profile of stimulant therapy as monotherapy and in combination in the central hypersomnias in clinical practice

Effectiveness and side-effect profile data on pharmacotherapy for daytime sleepiness in central hypersomnias are based largely upon randomized controlled trials. Evidence regarding the use of combination therapy is scant. The aim of this study was to examine the effectiveness and occurrence of drug-related side effects of these drugs in routine clinical practice. Adult patients diagnosed with a central hypersomnia during a 54-month period at a tertiary sleep disorders centre were identified retrospectively. Side effects were recorded at every follow-up visit. A total of 126 patients, with 3275 patient-months of drug exposure, were categorized into narcolepsy type 1 (n = 70), narcolepsy type 2 (n = 47) and idiopathic hypersomnia (n = 9). Modafinil was the most common drug used as a first-line treatment (93%) and in combination therapy (70%). Thirty-nine per cent of the patients demonstrated a complete, 25% partial and 36% a poor response to treatment. Combination treatment improved daytime sleepiness in 55% of the patients with residual symptoms despite monotherapy. Sixty per cent of patients reported side effects, and 30% reported treatment-limiting side effects. Drugs had similar side-effect incidence (P = 0.363) and their side-effect profile met those reported in the literature. Twenty-seven per cent of the patients received combination treatment and had fewer side effects compared to monotherapy (29.4% versus 60%, respectively, P = 0.001). Monotherapy appears to achieve satisfactory symptom control in most patients with central hypersomnia, but significant side effects are common. Combination therapy appears to be a useful and safe option in patients with refractory symptoms

Air quality-related human health damages of wild capture seafood production in the United States

Exposure to air pollution is the greatest environmental health risk factor for mortality in the United States and globally, to which food production is a major contributor. Recent studies have estimated the human health impacts of air pollution from terrestrial livestock and crop production, but those of seafood production, which is an important component of many diets, are largely unknown. Here, we estimate the air quality-related human health damages of wild capture fisheries production in the United States via the emission and formation of particulate matter (PM<jats:sub/>2.5). We quantify annual deaths attributable to primary and secondary PM<jats:sub/>2.5 from commercial marine vessel emissions using county- and species-specific fishing activity and landings data. We find that, on average, wild caught seafood production is a low air quality-related health impact source of protein, with mortality health impacts 58× less than chicken, 321× less than pork, and 484× less than beef per gram of protein. The air quality-related health impacts of seafood vary widely by species and by fishing activity location. Notably, the highest impact seafood-based sources of protein production tend to be far less damaging than terrestrial animal-based sources of protein and are comparable to plant-based proteins, largely mirroring previously described broader trends for the life cycle greenhouse gas emissions of these various protein sources. Our work suggests that as global protein demand rises, shifting diets towards increased seafood consumption to meet nutritional protein requirements may offer potentially large reductions in environmentally driven harm to human health relative to terrestrial animal-based proteins

Ultradian rhythmicity of plasma cortisol is necessary for normal emotional and cognitive responses in man

Glucocorticoids (GCs) are secreted in an ultradian, pulsatile pattern that emerges from delays in the feedforward-feedback interaction between the anterior pituitary and adrenal glands. Dynamic oscillations of GCs are critical for normal cognitive and metabolic function in the rat and have been shown to modulate the pattern of GC-sensitive gene expression, modify synaptic activity, and maintain stress responsiveness. In man, current cortisol replacement therapy does not reproduce physiological hormone pulses and is associated with psychopathological symptoms, especially apathy and attenuated motivation in engaging with daily activities. In this work, we tested the hypothesis that the pattern of GC dynamics in the brain is of crucial importance for regulating cognitive and behavioral processes. We provide evidence that exactly the same dose of cortisol administered in different patterns alters the neural processing underlying the response to emotional stimulation, the accuracy in recognition and attentional bias toward/away from emotional faces, the quality of sleep, and the working memory performance of healthy male volunteers. These data indicate that the pattern of the GC rhythm differentially impacts human cognition and behavior under physiological, nonstressful conditions and has major implications for the improvement of cortisol replacement therapy

Combinatorial hydrogel library enables identification of materials that mitigate the foreign body response in primates

The foreign body response is an immune-mediated reaction that can lead to the failure of implanted medical devices and discomfort for the recipient. There is a critical need for biomaterials that overcome this key challenge in the development of medical devices. Here we use a combinatorial approach for covalent chemical modification to generate a large library of variants of one of the most widely used hydrogel biomaterials, alginate. We evaluated the materials in vivo and identified three triazole-containing analogs that substantially reduce foreign body reactions in both rodents and, for at least 6 months, in non-human primates. The distribution of the triazole modification creates a unique hydrogel surface that inhibits recognition by macrophages and fibrous deposition. In addition to the utility of the compounds reported here, our approach may enable the discovery of other materials that mitigate the foreign body response.Leona M. and Harry B. Helmsley Charitable Trust (3-SRA-2014-285-M-R)United States. National Institutes of Health (EB000244)United States. National Institutes of Health (EB000351)United States. National Institutes of Health (DE013023)United States. National Institutes of Health (CA151884)United States. National Institutes of Health (P41EB015871-27)National Cancer Institute (U.S.) (P30-CA14051

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

The meso scale as a frontier in interdisciplinary modeling of sustainability from local to global scales

Achieving sustainable development requires understanding how human behavior and the environment interact across spatial scales. In particular, knowing how to manage tradeoffs between the environment and the economy, or between one spatial scale and another, necessitates a modeling approach that allows these different components to interact. Existing integrated local and global analyses provide key insights, but often fail to capture 'meso-scale' phenomena that operate at scales between the local and the global, leading to erroneous predictions and a constrained scope of analysis. Meso-scale phenomena are difficult to model because of their complexity and computational challenges, where adding additional scales can increase model run-time exponentially. These additions, however, are necessary to make models that include sufficient detail for policy-makers to assess tradeoffs. Here, we synthesize research that explicitly includes meso-scale phenomena and assess where further efforts might be fruitful in improving our predictions and expanding the scope of questions that sustainability science can answer. We emphasize five categories of models relevant to sustainability science, including biophysical models, integrated assessment models, land-use change models, earth-economy models and spatial downscaling models. We outline the technical and methodological challenges present in these areas of research and discuss seven directions for future research that will improve coverage of meso-scale effects. Additionally, we provide a specific worked example that shows the challenges present, and possible solutions, for modeling meso-scale phenomena in integrated earth-economy models

Determining the impact of an artificial intelligence tool on the management of pulmonary nodules detected incidentally on CT (DOLCE) study protocol: a prospective, non-interventional multicentre UK study

\ua9 Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. INTRODUCTION: In a small percentage of patients, pulmonary nodules found on CT scans are early lung cancers. Lung cancer detected at an early stage has a much better prognosis. The British Thoracic Society guideline on managing pulmonary nodules recommends using multivariable malignancy risk prediction models to assist in management. While these guidelines seem to be effective in clinical practice, recent data suggest that artificial intelligence (AI)-based malignant-nodule prediction solutions might outperform existing models. METHODS AND ANALYSIS: This study is a prospective, observational multicentre study to assess the clinical utility of an AI-assisted CT-based lung cancer prediction tool (LCP) for managing incidental solid and part solid pulmonary nodule patients vs standard care. Two thousand patients will be recruited from 12 different UK hospitals. The primary outcome is the difference between standard care and LCP-guided care in terms of the rate of benign nodules and patients with cancer discharged straight after the assessment of the baseline CT scan. Secondary outcomes investigate adherence to clinical guidelines, other measures of changes to clinical management, patient outcomes and cost-effectiveness. ETHICS AND DISSEMINATION: This study has been reviewed and given a favourable opinion by the South Central-Oxford C Research Ethics Committee in UK (REC reference number: 22/SC/0142).Study results will be available publicly following peer-reviewed publication in open-access journals. A patient and public involvement group workshop is planned before the study results are available to discuss best methods to disseminate the results. Study results will also be fed back to participating organisations to inform training and procurement activities. TRIAL REGISTRATION NUMBER: NCT05389774