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St Peter's Hospital

Hospital / health systemChertsey, England, United Kingdom

Research output, citation impact, and the most-cited recent papers from St Peter's Hospital (United Kingdom). Aggregated across the NobleBlocks index of 300M+ scholarly works.

Total works
1.2K
Citations
61.9K
h-index
116
i10-index
878
Also known as
St Peter's Hospital

Top-cited papers from St Peter's Hospital

Summary of the Recommendations on Sexual Dysfunctions in Men
Francesco Montorsi, Ganesan Adaikan, Edgardo Becher, François Giuliano +4 more
2010· The Journal of Sexual Medicine933doi:10.1111/j.1743-6109.2010.02062.x

INTRODUCTION: Sexual health is an integral part of overall health. Sexual dysfunction can have a major impact on quality of life and psychosocial and emotional well-being. AIM: To provide evidence-based, expert-opinion consensus guidelines for clinical management of sexual dysfunction in men. METHODS: An international consultation collaborating with major urologic and sexual medicine societies convened in Paris, July 2009. More than 190 multidisciplinary experts from 33 countries were assembled into 25 consultation committees. Committee members established scope and objectives for each chapter. Following an exhaustive review of available data and publications, committees developed evidence-based guidelines in each area. Main Outcome Measures. New algorithms and guidelines for assessment and treatment of sexual dysfunctions were developed based on work of previous consultations and evidence from scientific literature published from 2003 to 2009. The Oxford system of evidence-based review was systematically applied. Expert opinion was based on systematic grading of medical literature, and cultural and ethical considerations. RESULTS: Algorithms, recommendations, and guidelines for sexual dysfunction in men are presented. These guidelines were developed in an evidence-based, patient-centered, multidisciplinary manner. It was felt that all sexual dysfunctions should be evaluated and managed following a uniform strategy, thus the International Consultation of Sexual Medicine (ICSM-5) developed a stepwise diagnostic and treatment algorithm for sexual dysfunction. The main goal of ICSM-5 is to unmask the underlying etiology and/or indicate appropriate treatment options according to men's and women's individual needs (patient-centered medicine) using the best available data from population-based research (evidence-based medicine). Specific evaluation, treatment guidelines, and algorithms were developed for every sexual dysfunction in men, including erectile dysfunction; disorders of libido, orgasm, and ejaculation; Peyronie's disease; and priapism. CONCLUSIONS: Sexual dysfunction in men represents a group of common medical conditions that need to be managed from a multidisciplinary perspective.

Inflammation as a causative factor in the aetiology of Parkinson's disease
Peter S. Whitton
2007· British Journal of Pharmacology629doi:10.1038/sj.bjp.0707167

Parkinson's disease (PD) is a progressive neurodegenerative disorder affecting mainly the elderly, although a small proportion of PD patients develop the illness at a much younger age. In the former group, idiopathic PD patients, the causes of the illness have been the subject of longstanding debate with environmental toxins, mitochondrial dysfunction, abnormal protein handling and oxidative stress being suggested. One problem has been that the epidemiology of PD has offered few clues to provide evidence for a single major causative factor. Comparatively recently it has been found that in both patients and experimental models of PD in animals neuroinflammation appears to be a ubiquitous finding. These cases present with all of the classical features of inflammation including phagocyte activation, increased synthesis and release of proinflammatory cytokines and complement activation. Although this process is vital for normal function and protection in both the CNS, as in the periphery, it is postulated that in the aetiology of PD this process may spiral out of control with over activation of microglia, over production of cytokines and other proinflammatory mediators as well as the release of destructive molecules such as reactive oxygen species. Given that dopaminergic neurons in the substantia nigra are relatively vulnerable to 'stress' and the region has a large population of microglia in comparison to other CNS structures, these events may easily trigger neurodegeneration. These factors are examined in this review along with a consideration of the possible use of anti-inflammatory drugs in PD.

Efficacy and Safety of Daily Risedronate in the Treatment of Corticosteroid-Induced Osteoporosis in Men and Women: A Randomized Trial
David M. Reid, Rodney Hughes, Roland Laan, N. Sacco-Gibson +4 more
2000· Journal of Bone and Mineral Research593doi:10.1359/jbmr.2000.15.6.1006

Long-term use of high-dose corticosteroids often results in bone loss, which may lead to osteoporosis-related fractures. This was a multicenter, double-blind study in which 290 ambulatory men and women receiving high-dose oral corticosteroid therapy (prednisone > or = 7.5 mg/day or equivalent) for 6 or more months were randomized to receive placebo, risedronate 2.5 mg/day, or risedronate 5 mg/day for 12 months. All patients received calcium 1 g and vitamin D 400 IU daily. The primary endpoint was lumbar spine bone mineral density (BMD) at month 12. Additional measurements included BMD at the femoral neck and trochanter and the incidence of vertebral fractures. Overall, there were statistically significant treatment effects on BMD at 12 months at the lumbar spine (p < 0.001), femoral neck (p = 0.004), and trochanter (p = 0.010). Risedronate 5 mg increased BMD at 12 months by a mean (SEM) of 2.9% (0.49%) at the lumbar spine, 1.8% (0.46%) at the femoral neck, and 2.4% (0.54%) at the trochanter, whereas BMD was maintained only in the control group. Although not powered to show fracture efficacy, we observed a reduction in the incidence of vertebral fractures of 70% in the combined risedronate treatment groups, relative to placebo (p = 0.042). Risedronate was well tolerated, had a good safety profile, and was not associated with gastrointestinal adverse events. We conclude that risedronate increases BMD and potentially reduces the incidence of vertebral fractures in patients with corticosteroid-induced osteoporosis.

Cancer of the ovary, fallopian tube, and peritoneum: 2021 update
Jonathan S. Berek, Malte Renz, Sean Kehoe, Lalit Kumar +1 more
2021· International Journal of Gynecology & Obstetrics494doi:10.1002/ijgo.13878

In 2014, FIGO's Committee for Gynecologic Oncology revised the staging of ovarian cancer, incorporating ovarian, fallopian tube, and peritoneal cancer into the same system. Most of these malignancies are high-grade serous carcinomas (HGSC). Stage IC is now divided into three categories: IC1 (surgical spill); IC2 (capsule ruptured before surgery or tumor on ovarian or fallopian tube surface); and IC3 (malignant cells in the ascites or peritoneal washings). The updated staging includes a revision of Stage IIIC based on spread to the retroperitoneal lymph nodes alone without intraperitoneal dissemination. This category is now subdivided into IIIA1(i) (metastasis ≤10 mm in greatest dimension), and IIIA1(ii) (metastasis >10 mm in greatest dimension). Stage IIIA2 is now "microscopic extrapelvic peritoneal involvement with or without positive retroperitoneal lymph node" metastasis. This review summarizes the genetics, surgical management, chemotherapy, and targeted therapies for epithelial cancers, and the treatment of ovarian germ cell and stromal malignancies.

An Evidence-Based Unified Definition of Lifelong and Acquired Premature Ejaculation: Report of the Second International Society for Sexual Medicine Ad Hoc Committee for the Definition of Premature Ejaculation
Ege Can Şerefoğlu, Chris G. McMahon, Marcel D. Waldinger, Stanley E. Althof +4 more
2014· The Journal of Sexual Medicine464doi:10.1111/jsm.12524

INTRODUCTION: The International Society for Sexual Medicine (ISSM) Ad Hoc Committee for the Definition of Premature Ejaculation developed the first evidence-based definition for lifelong premature ejaculation (PE) in 2007 and concluded that there were insufficient published objective data at that time to develop a definition for acquired PE. AIM: The aim of this article is to review and critique the current literature and develop a contemporary, evidence-based definition for acquired PE and/or a unified definition for both lifelong and acquired PE. METHODS: In April 2013, the ISSM convened a second Ad Hoc Committee for the Definition of Premature Ejaculation in Bangalore, India. The same evidence-based systematic approach to literature search, retrieval, and evaluation used by the original committee was adopted. RESULTS: The committee unanimously agreed that men with lifelong and acquired PE appear to share the dimensions of short ejaculatory latency, reduced or absent perceived ejaculatory control, and the presence of negative personal consequences. Men with acquired PE are older, have higher incidences of erectile dysfunction, comorbid disease, and cardiovascular risk factors, and have a longer intravaginal ejaculation latency time (IELT) as compared with men with lifelong PE. A self-estimated or stopwatch IELT of 3 minutes was identified as a valid IELT cut-off for diagnosing acquired PE. On this basis, the committee agreed on a unified definition of both acquired and lifelong PE as a male sexual dysfunction characterized by (i) ejaculation that always or nearly always occurs prior to or within about 1 minute of vaginal penetration from the first sexual experience (lifelong PE) or a clinically significant and bothersome reduction in latency time, often to about 3 minutes or less (acquired PE); (ii) the inability to delay ejaculation on all or nearly all vaginal penetrations; and (iii) negative personal consequences, such as distress, bother, frustration, and/or the avoidance of sexual intimacy. CONCLUSION: The ISSM unified definition of lifelong and acquired PE represents the first evidence-based definition for these conditions. This definition will enable researchers to design methodologically rigorous studies to improve our understanding of acquired PE. Serefoglu EC, McMahon CG, Waldinger MD, Althof SE, Shindel A, Adaikan G, Becher EF, Dean J, Giuliano F, Hellstrom WJG, Giraldi A, Glina S, Incrocci L, Jannini E, McCabe M, Parish S, Rowland D, Segraves RT, Sharlip I, and Torres LO. An evidence-based unified definition of lifelong and acquired premature ejaculation: Report of the second International Society for Sexual Medicine Ad Hoc Committee for the Definition of Premature Ejaculation. Sex Med 2014;2:41-59.

An Update of the International Society of Sexual Medicine's Guidelines for the Diagnosis and Treatment of Premature Ejaculation (PE)
Stanley E. Althof, Chris G. McMahon, Marcel D. Waldinger, Ege Can Şerefoğlu +4 more
2014· Sexual Medicine434doi:10.1002/sm2.28

INTRODUCTION: In 2009, the International Society for Sexual Medicine (ISSM) convened a select panel of experts to develop an evidence-based set of guidelines for patients suffering from lifelong premature ejaculation (PE). That document reviewed definitions, etiology, impact on the patient and partner, assessment, and pharmacological, psychological, and combined treatments. It concluded by recognizing the continually evolving nature of clinical research and recommended a subsequent guideline review and revision every fourth year. Consistent with that recommendation, the ISSM organized a second multidisciplinary panel of experts in April 2013, which met for 2 days in Bangalore, India. This manuscript updates the previous guidelines and reports on the recommendations of the panel of experts. AIM: The aim of this study was to develop clearly worded, practical, evidenced-based recommendations for the diagnosis and treatment of PE for family practice clinicians as well as sexual medicine experts. METHOD: A comprehensive literature review was performed. RESULTS: This article contains the report of the second ISSM PE Guidelines Committee. It offers a new unified definition of PE and updates the previous treatment recommendations. Brief assessment procedures are delineated, and validated diagnostic and treatment questionnaires are reviewed. Finally, the best practices treatment recommendations are presented to guide clinicians, both familiar and unfamiliar with PE, in facilitating treatment of their patients. CONCLUSION: Development of guidelines is an evolutionary process that continually reviews data and incorporates the best new research. We expect that ongoing research will lead to a more complete understanding of the pathophysiology as well as new efficacious and safe treatments for this sexual dysfunction. We again recommend that these guidelines be reevaluated and updated by the ISSM in 4 years. Althof SE, McMahon CG, Waldinger MD, Serefoglu EC, Shindel AW, Adaikan PG, Becher E, Dean J, Giuliano F, Hellstrom WJG, Giraldi A, Glina S, Incrocci L, Jannini E, McCabe M, Parish S, Rowland D, Segraves RT, Sharlip I, and Torres LO. An update of the International Society of Sexual Medicine's guidelines for the diagnosis and treatment of premature ejaculation (PE). Sex Med 2014;2:60-90.

Whole-genome sequencing reveals host factors underlying critical COVID-19
Athanasios Kousathanas, Erola Pairo‐Castineira, Konrad Rawlik, A. Stuckey +4 more
2022· Nature344doi:10.1038/s41586-022-04576-6

after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes-including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)-in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease.

TRAIT EMOTIONAL INTELLIGENCE AND HAPPINESS
Adrian Furnham, K. V. Petrides
2003· Social Behavior and Personality An International Journal341doi:10.2224/sbp.2003.31.8.815

Participants completed measures of trait emotional intelligence (trait EI), happiness, personality, and cognitive ability. Neuroticism was negatively related to happiness, whereas Extraversion and Openness to Experience were positively related to it. Cognitive ability was not related either to happiness or to trait EI. A three-step hierarchical regression showed that trait EI explained over 50% of the total variance in happiness. The positive relationship between trait EI and happiness persisted in the presence of the Big Five. In contrast, the Big Five did not account for a significant amount of happiness variance when trait EI was partialled out.

Better Rules or Stronger Communities? On the Social Foundations of Institutional Change and Its Economic Effects
Andrés Rodríguez‐Pose, Michael Storper
2006· Economic Geography292doi:10.1111/j.1944-8287.2006.tb00286.x

Abstract: Much of the literature on the impact of institutions on economic development has focused on the tradeoffs between society and community as mutually opposed forms of institutional coordination. On the one hand, sociologists, geographers, and some economists have stressed the positive economic externalities that are associated with the development of associational or group life. Most economists, in contrast, hold that the development of communities may be a second‐best solution to the development of formal institutions or even have negative effects, such as the promotion of rent‐seeking behavior and principal‐agent problems. Societal institutions—such as clear, transparent rules and enforcement mechanisms—are held to be universally positive for development. But there are no real‐world cases in which only one of the two exists; society and community are always and everywhere in interaction. This interaction, however, has attracted little attention. In this article, society and community are conceived of as complementary forms of organization whose relative balance and interaction shape the economic potential of every territory. Changes in the balance between community and society take place constantly and affect the medium‐ and long‐run development prospects of every territory. The depth and the speed of change depend on a series of factors, such as starting points in the interaction of society and community, the sources and dynamics of change, and the conflict‐solving capacities of the preexisting situation.

Developing by borrowing? Inter-jurisdictional competition, land finance and local debt accumulation in China
Fenghua Pan, Fengmei Zhang, Shengjun Zhu, Dariusz Wójcik
2016· Urban Studies281doi:10.1177/0042098015624838

Although the investment-oriented development model for economic growth adopted by Chinese governments has generated spectacular results, the risks of debt-financed urbanisation and economic development have recently become evident in mounting local debts that are undermining the financial system, triggering concerns with respect to local governments’ indebtedness, financial stability and sovereign risk in China. In this paper, we portray the uneven spatial and temporal dynamics of local government debt in China, and examine the ways in which it is intertwined with institutional, political and economic factors. Our analysis shows that while global and national economic conditions have resulted in a dramatic increase in local government debt, particularly in the late 2000s and the early 2010s, the spatial variation of local debt accumulation in China could be partly explained by two institutional factors: land finance and inter-jurisdictional competition. We argue that the behaviour of local governments may harm the long-term future of Chinese cities.

Patients and professionals as research partners: Challenges, practicalities, and benefits
Sarah Hewlett, Maarten de Wit, P. Scott Richards, Enid Quest +3 more
2006· Arthritis Care & Research275doi:10.1002/art.22091

Patient or consumer involvement in research is widely recommended, but although guidelines for researchers and patients have been produced, few practical experiences have been published and involvement remains fragile. This article reports the combined experiences of researchers and patients who are collaborating in rheumatology research, and the working model that has evolved. The article provides one example of a practical model for collaboration based on experience.

An Update of the International Society of Sexual Medicine's Guidelines for the Diagnosis and Treatment of Premature Ejaculation (PE)
Stanley E. Althof, Chris G. McMahon, Marcel D. Waldinger, Ege Can Şerefoğlu +4 more
2014· The Journal of Sexual Medicine273doi:10.1111/jsm.12504

INTRODUCTION: In 2009, the International Society for Sexual Medicine (ISSM) convened a select panel of experts to develop an evidence-based set of guidelines for patients suffering from lifelong premature ejaculation (PE). That document reviewed definitions, etiology, impact on the patient and partner, assessment, and pharmacological, psychological, and combined treatments. It concluded by recognizing the continually evolving nature of clinical research and recommended a subsequent guideline review and revision every fourth year. Consistent with that recommendation, the ISSM organized a second multidisciplinary panel of experts in April 2013, which met for 2 days in Bangalore, India. This manuscript updates the previous guidelines and reports on the recommendations of the panel of experts. AIM: The aim of this study was to develop clearly worded, practical, evidenced-based recommendations for the diagnosis and treatment of PE for family practice clinicians as well as sexual medicine experts. METHOD: A comprehensive literature review was performed. RESULTS: This article contains the report of the second ISSM PE Guidelines Committee. It offers a new unified definition of PE and updates the previous treatment recommendations. Brief assessment procedures are delineated, and validated diagnostic and treatment questionnaires are reviewed. Finally, the best practices treatment recommendations are presented to guide clinicians, both familiar and unfamiliar with PE, in facilitating treatment of their patients. CONCLUSION: Development of guidelines is an evolutionary process that continually reviews data and incorporates the best new research. We expect that ongoing research will lead to a more complete understanding of the pathophysiology as well as new efficacious and safe treatments for this sexual dysfunction. We again recommend that these guidelines be reevaluated and updated by the ISSM in 4 years.

An Evidence-Based Unified Definition of Lifelong and Acquired Premature Ejaculation: Report of the Second International Society for Sexual Medicine Ad Hoc Committee for the Definition of Premature Ejaculation
Ege Can Şerefoğlu, Chris G. McMahon, Marcel D. Waldinger, Stanley E. Althof +4 more
2014· Sexual Medicine265doi:10.1002/sm2.27

Abstract Introduction The International Society for Sexual Medicine (ISSM) Ad Hoc Committee for the Definition of Premature Ejaculation developed the first evidence-based definition for lifelong premature ejaculation (PE) in 2007 and concluded that there were insufficient published objective data at that time to develop a definition for acquired PE. Aim The aim of this article is to review and critique the current literature and develop a contemporary, evidence-based definition for acquired PE and/or a unified definition for both lifelong and acquired PE. Methods In April 2013, the ISSM convened a second Ad Hoc Committee for the Definition of Premature Ejaculation in Bangalore, India. The same evidence-based systematic approach to literature search, retrieval, and evaluation used by the original committee was adopted. Results The committee unanimously agreed that men with lifelong and acquired PE appear to share the dimensions of short ejaculatory latency, reduced or absent perceived ejaculatory control, and the presence of negative personal consequences. Men with acquired PE are older, have higher incidences of erectile dysfunction, comorbid disease, and cardiovascular risk factors, and have a longer intravaginal ejaculation latency time (IELT) as compared with men with lifelong PE. A self-estimated or stopwatch IELT of 3 minutes was identified as a valid IELT cut-off for diagnosing acquired PE. On this basis, the committee agreed on a unified definition of both acquired and lifelong PE as a male sexual dysfunction characterized by (i) ejaculation that always or nearly always occurs prior to or within about 1 minute of vaginal penetration from the first sexual experience (lifelong PE) or a clinically significant and bothersome reduction in latency time, often to about 3 minutes or less (acquired PE); (ii) the inability to delay ejaculation on all or nearly all vaginal penetrations; and (iii) negative personal consequences, such as distress, bother, frustration, and/or the avoidance of sexual intimacy. Conclusion The ISSM unified definition of lifelong and acquired PE represents the first evidence-based definition for these conditions. This definition will enable researchers to design methodologically rigorous studies to improve our understanding of acquired PE.

Guidelines for the management of lichen sclerosus
S. Neill, F.M. Tatnall, N.H. Cox
2002· British Journal of Dermatology223doi:10.1046/j.1365-2133.2002.05012.x

These guidelines for the management of lichen sclerosus have been prepared for dermatologists on behalf of the British Association of Dermatologists. They present evidence-based guidance for treatment, with identification of the strength of evidence available at the time of preparation of the guidelines, and a brief overview of epidemiological aspects, diagnosis and investigation.

Outcome of penile prosthesis implantation for treating erectile dysfunction: experience with 504 procedures
Andrea Minervini, David Ralph, John P. Pryor
2005· British Journal of Urology221doi:10.1111/j.1464-410x.2005.05907.x

OBJECTIVE: To evaluate the outcome of penile prosthesis surgery for different types of prosthesis. PATIENTS AND METHODS: The notes of 447 men who had 504 penile prosthesis implanted between August 1975 and December 2000 were evaluated. Of the prostheses inserted, 393 were malleable, 81 were three-piece inflatable and 30 were self-contained hydraulic prostheses. The mean (range) age of the men was 52 (21-78) years; 404 men had primary implants and 43 had revision surgery after operations at other institutions. The mean follow-up was 50 (1-297) months. RESULTS: Of the 447 men, 22 were lost to follow-up immediately after surgery. The most serious postoperative complications were infection (8%) and erosion (5%), which was more common in diabetic patients (10%) and after pelvic trauma with a urethral injury (21%). Of 482 prostheses, 21 failed mechanically (4%) and revision surgery was needed for 5% of the prostheses inserted (24/482). Overall, 89% (377/425) of men could have sexual intercourse and 344 (81%) were satisfied with the results. CONCLUSIONS: Of the men implanted with a penile prosthesis, 81% were satisfied with the outcome and an even higher proportion were satisfied with the inflatable prostheses. Dissatisfaction was mainly due to complications that resulted in removal of the prosthesis.

GWAS and meta-analysis identifies 49 genetic variants underlying critical COVID-19
Erola Pairo‐Castineira, Konrad Rawlik, Andrew D. Bretherick, Ting Qi +4 more
2023· Nature200doi:10.1038/s41586-023-06034-3

Abstract Critical illness in COVID-19 is an extreme and clinically homogeneous disease phenotype that we have previously shown 1 to be highly efficient for discovery of genetic associations 2 . Despite the advanced stage of illness at presentation, we have shown that host genetics in patients who are critically ill with COVID-19 can identify immunomodulatory therapies with strong beneficial effects in this group 3 . Here we analyse 24,202 cases of COVID-19 with critical illness comprising a combination of microarray genotype and whole-genome sequencing data from cases of critical illness in the international GenOMICC (11,440 cases) study, combined with other studies recruiting hospitalized patients with a strong focus on severe and critical disease: ISARIC4C (676 cases) and the SCOURGE consortium (5,934 cases). To put these results in the context of existing work, we conduct a meta-analysis of the new GenOMICC genome-wide association study (GWAS) results with previously published data. We find 49 genome-wide significant associations, of which 16 have not been reported previously. To investigate the therapeutic implications of these findings, we infer the structural consequences of protein-coding variants, and combine our GWAS results with gene expression data using a monocyte transcriptome-wide association study (TWAS) model, as well as gene and protein expression using Mendelian randomization. We identify potentially druggable targets in multiple systems, including inflammatory signalling ( JAK1 ), monocyte–macrophage activation and endothelial permeability ( PDE4A ), immunometabolism ( SLC2A5 and AK5 ), and host factors required for viral entry and replication ( TMPRSS2 and RAB2A ).

Hypoxia and angiogenesis in rheumatoid arthritis
Peter C. Taylor, Bran Sivakumar
2005· Current Opinion in Rheumatology188doi:10.1097/01.bor.0000155361.83990.5b

PURPOSE OF REVIEW: Angiogenesis is a prominent feature of rheumatoid synovitis. Although new blood vessels deliver oxygen to the augmented inflammatory cell mass, the neovascular network is dysfunctional and fails to restore tissue oxygen homeostasis, so that the rheumatoid joint remains a markedly hypoxic environment. The purpose of this review is to discuss the role of hypoxia and angiogenesis in the pathogenesis of rheumatoid arthritis. RECENT FINDINGS: Vascular pathologic change, in the form of angiogenesis, is important in the perpetuation of rheumatoid arthritis and, in the form of endothelial dysfunction, contributes to associated cardiovascular comorbidity. Recent data suggest that tumor necrosis factor-alpha blockade may modify the vascular pathologic changes in rheumatoid arthritis. Angiogenesis is a prominent feature of rheumatoid synovitis. Emerging evidence based on ultrasonographic vascular imaging and angiogenic biomarkers implicates angiogenesis in the active phase of erosive disease. Many factors contribute to the profoundly hypoxic environment that can arise within the joint affected by rheumatoid arthritis. At a cellular level, hypoxia is detected by a mechanism that regulates cytoplasmic concentrations of hypoxia-inducible factor-1alpha. After translocation to the nucleus, hypoxia-inducible factor-1alpha binds its partner hypoxia-inducible factor-1beta to form a heterodimeric, functional transcription factor, hypoxia-inducible factor-1, which activates a gene program associated with angiogenesis, glycolysis, and adaptation to pH. SUMMARY: Despite the luxuriant vasculature associated with rheumatoid arthritis synovitis, the joint affected by rheumatoid arthritis is hypoxic. Repetitive cycles of hypoxia and reoxygenation together with oxidants produced by phagocytic cells promote chronic oxidative stress within the microenvironment of the affected joint, leading to the generation of reactive oxygen species with the potential to contribute to tissue damage.

Burden of disease attributable to high body mass index: an analysis of data from the Global Burden of Disease Study 2021
Xiaodong Zhou, Qin‐Fen Chen, Wah Yang, Mauricio Zuluaga +4 more
2024· EClinicalMedicine186doi:10.1016/j.eclinm.2024.102848

Background: Obesity represents a major global health challenge with important clinical implications. Despite its recognized importance, the global disease burden attributable to high body mass index (BMI) remains less well understood. Methods: for individuals aged ≥20 years. The Socio-Demographic Index (SDI) was used as a composite measure to assess the level of socio-economic development across different regions. Subgroup analyses considered age, sex, year, geographical location, and SDI. Findings: From 1990 to 2021, the global deaths and DALYs attributable to high BMI increased more than 2.5-fold for females and males. However, the age-standardized death rates remained stable for females and increased by 15.0% for males. Similarly, the age-standardized DALY rates increased by 21.7% for females and 31.2% for males. In 2021, the six leading causes of high BMI-attributable DALYs were diabetes mellitus, ischemic heart disease, hypertensive heart disease, chronic kidney disease, low back pain and stroke. From 1990 to 2021, low-middle SDI countries exhibited the highest annual percentage changes in age-standardized DALY rates, whereas high SDI countries showed the lowest. Interpretation: The worldwide health burden attributable to high BMI has grown significantly between 1990 and 2021. The increasing global rates of high BMI and the associated disease burden highlight the urgent need for regular surveillance and monitoring of BMI. Funding: National Natural Science Foundation of China and National Key R&D Program of China.

A twelve month comparison of salmeterol with salbutamol in asthmatic patients. European Study Group
MG Britton, JS Earnshaw, JB Palmer
1992· European Respiratory Journal181doi:10.1183/09031936.93.05091062

The efficacy and tolerability of salmeterol, 50 micrograms b.i.d. was compared for three months with salbutamol, 200 micrograms q.i.d., administered from metered-dose inhaler. For the following nine months, safety and clinic lung function was monitored on salmeterol, 50 micrograms b.i.d., compared with salbutamol, 200 micrograms b.i.d. This comparison was made in a multicentre, double-blind, parallel-group study of 667 moderate asthmatics, who had a forced expiratory volume in one second (FEV1) or peak expiratory flow rate (PEFR) > 50% predicted, a 15% reversibility to inhaled salbutamol and who were experiencing symptoms. Throughout the first three month treatment period, both morning and evening PEFR were significantly higher on treatment with salmeterol than salbutamol (mean differences between the treatments 30 l.min-1 for morning, p < 0.001, and 11 l.min-1 for evening, p < 0.01). In addition, the diurnal variation in PEFR, nocturnal and daytime symptoms and use of additional salbutamol were significantly lower in the salmeterol treated group. This improvement was also apparent in the separate subpopulations of patients taking no concurrent glucocorticosteroid or concurrent inhaled and/or oral glucocorticosteroids. Both treatments were well-tolerated throughout the 12 months of treatment. There was a lower incidence of asthma and related events during salmeterol treatment compared to salbutamol treatment subgroups. The results of the study clearly demonstrate that salmeterol, 50 micrograms b.i.d., is well-tolerated and more effective than salbutamol, 200 micrograms q.i.d., in the treatment of moderate asthma.

Myocutaneous flap reconstruction of the pelvis after abdominoperineal excision
Pasha J. Nisar, H J Scott
2008· Colorectal Disease180doi:10.1111/j.1463-1318.2008.01743.x

OBJECTIVE: Perineal wound complications after abdominoperineal excision (APE) for anorectal cancer represent a considerable source of morbidity for patients. Strategies to improve wound healing include reconstruction with myocutaneous flaps. This is an evidence-based review of reconstruction of pelvic defects after APE, using rectus abdominus (RAM), gracilis and gluteus maximus flaps. METHOD: A Pubmed search was performed using MESH headings. RESULTS: Thirty-six studies reported outcomes of interest. Five controlled studies reported improved outcomes after APE and chemoradiotherapy with RAM reconstruction and two controlled studies reported improved outcomes with gracilis reconstruction. There were seven patients with total flap loss after RAM reconstruction, in a combined 300 patients. There were eight patients with complete cutaneous necrosis after gracilis reconstruction in a combined 83 patients. CONCLUSION: Data from the controlled studies support the use of myocutaneous flaps for single-stage reconstruction after APE in the presence of chemoradiotherapy. Ultimately, the choice of flap depends on the goals of reconstruction, size of the defect and the availability of donor tissue. The implications of an expanding role for radiotherapy in the treatment of low rectal cancer and radical dissection to achieve negative circumferential margins, necessitate close co-operation between colorectal and reconstructive surgeons to achieve APE with reduced wound morbidity.