Fixed-intensity exercise tests to measure exertional dyspnoea in chronic heart and lung populations: a systematic review

Introduction Exertional dyspnoea is the primary diagnostic symptom for chronic cardiopulmonary disease populations. Whilst a number of exercise tests are used, there remains no gold standard clinical measure of exertional dyspnoea. The aim of this review was to comprehensively describe and evaluate all types of fixed-intensity exercise tests used to assess exertional dyspnoea in chronic cardiopulmonary populations and, where possible, report the reliability and responsiveness of the tests. Methods A systematic search of five electronic databases identified papers that examined 1) fixed-intensity exercise tests and measured exertional dyspnoea, 2) chronic cardiopulmonary populations, 3) exertional dyspnoea reported at isotime or upon completion of fixed-duration exercise tests, and 4) published in English. Results Searches identified 8785 papers. 123 papers were included, covering exercise tests using a variety of fixed-intensity protocols. Three modes were identified, as follows: 1) cycling (n=87), 2) walking (n=31) and 3) other (step test (n=8) and arm exercise (n=2)). Most studies (98%) were performed on chronic respiratory disease patients. Nearly all studies (88%) used an incremental exercise test. 34% of studies used a fixed duration for the exercise test, with the remaining 66% using an exhaustion protocol recording exertional dyspnoea at isotime. Exertional dyspnoea was measured using the Borg scale (89%). 7% of studies reported reliability. Most studies (72%) examined the change in exertional dyspnoea in response to different interventions. Conclusion Considerable methodological variety of fixed-intensity exercise tests exists to assess exertional dyspnoea and most test protocols require incremental exercise tests. There does not appear to be a simple, universal test for measuring exertional dyspnoea in the clinical setting

Bone flap infections after craniotomy. a review of 63 cases and the implications for definitions, classification and surveillance methodologies

Background: Bone flap infections (BFI) occur following neurosurgical procedures such as craniotomies. However, they are poorly defined and often not clearly differentiated from other surgical site infection neurosurgery. Aim: To review data from a national adult neurosurgical centre to explore some clinical aspects to better inform definitions, classification and surveillance methodologies. Methods: We retrospectively reviewed data on clinical samples sent for culture from patients with suspected BFI. We also accessed information recorded prospectively from national and local databases for evidence of BFI or related conditions based upon terms used in surgical operative notes or discharge summaries and documented monomicrobial and polymicrobial infections related to craniotomy sites. Findings: Between January 2016 and December 2020, we documented 63 patients with a mean age of 45 years (16-80). Craniectomy for infection of the skull was the most common terminology used to describe BFI in the coding used in a national database, 40/63 (63%), but other terms were used. A malignant neoplasm was the most common underlying condition necessitating craniectomy in 28/63 (44%) cases. Specimens submitted for microbiological investigation included 48/63 (76%) bone flaps, 38/63 (60%) fluid/pus, and 29/63 (46%) tissue. Fifty-eight (92%) patients had at least one culture positive specimen; 32 (55%) were monomicrobial and 26 (45%) were polymicrobial. Gram-positive bacteria predominated and Staphylococcus aureus was the most common. Conclusion: Greater clarity on how to define BFI is required to enable better classification and the carrying out of appropriate surveillance. This will inform preventative strategies and more effective patient management.</p

Fetoscopic laser ablation for twin-to-twin transfusion syndrome: a 15-year review of perinatal survival

Objective Twin to twin transfusion syndrome (TTTS) complicates 5-15% of monochorionic twin pregnancies and untreated is associated with a 90% mortality rate. The aim was to present the perinatal survival of patients with TTTS treated with laser ablation, by a national fetal medicine team. Methods This was a review of all cases of TTTS treated with fetoscopic laser ablation performed from March 2006 through to December 2020. All patients treated with fetoscopic laser were identified from the hospital database. The perinatal outcomes for the overall cohort and the individual Quintero stages were determined. Results A total of 155 cases of TTTS underwent fetoscopic laser ablation during the study period. The median gestational age at diagnosis was 19+1 weeks, with a mean growth discordance of 23.6%. The Quintero stage at diagnosis was: Stage 1 6.5% (10/155), Stage 2 49% (76/155), Stage 3 38.7% (60/155), Stage 45.8% (9/155). There was at least one survivor in 83.2% (129/155) of pregnancies, with dual survival in 52.9% (82/155). An increase in the rate of any survivor was observed from 75% (2006-2014) to 94% (2014-2020) (p Conclusion Fetoscopic laser ablation is the recommended first line treatment for severe TTTS. We observed a survival rate of at least one twin in 83.2% pregnancies which is comparable to internationally published data on single-centre outcomes.</p

Rate of AIDS diseases or death in HIV-infected antiretroviral therapy-naïve individuals with high CD4 cell count

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Cancer chemoprevention: Evidence of a nonlinear dose response for the protective effects of resveratrol in humans and mice

Resveratrol is widely promoted as a potential cancer chemopreventive agent, but a lack of information on the optimal dose prohibits rationally designed trials to assess efficacy. To challenge the assumption that "more is better," we compared the pharmacokinetics and activity of a dietary dose with an intake 200 times higher. The dose-response relationship for concentrations generated and the metabolite profile of [(14)C]-resveratrol in colorectal tissue of cancer patients helped us to define clinically achievable levels. In Apc(Min) mice (a model of colorectal carcinogenesis) that received a high-fat diet, the low resveratrol dose suppressed intestinal adenoma development more potently than did the higher dose. Efficacy correlated with activation of adenosine monophosphate-activated protein kinase (AMPK) and increased expression of the senescence marker p21. Nonlinear dose responses were observed for AMPK and mechanistic target of rapamycin (mTOR) signaling in mouse adenoma cells, culminating in autophagy and senescence. In human colorectal tissues exposed to low dietary concentrations of resveratrol ex vivo, we measured enhanced AMPK phosphorylation and autophagy. The expression of the cytoprotective NAD(P)H dehydrogenase, quinone 1 (NQO1) enzyme was also increased in tissues from cancer patients participating in our [(14)C]-resveratrol trial. These findings warrant a revision of developmental strategies for diet-derived agents designed to achieve cancer chemoprevention