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Mikaela L Jorgensen,1 Jane M Young,1,2 Michael J Solomon2,3 1Cancer Epidemiology and Services Research (CESR), Sydney School of Public Health, Sydney Medical School, University of Sydney, Sydney, NSW, Australia; 2Surgical Outcomes Research Centre (SOuRCe), Sydney Local Health District and University of Sydney, Sydney, NSW, Australia; 3Discipline of Surgery, University of Sydney, Sydney, NSW, Australia Abstract: Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide. With population aging and increases in survival, the number of CRC survivors is projected to rise dramatically. The time following initial treatment is often described as a period of transition from intensive hospital-based care back into “regular life.” This review provides an overview of recommended follow-up care for people with CRC who have been treated with curative intent, as well as exploring the current state of the research that underpins these guidelines. For patients, key concerns following treatment include the development of recurrent and new cancers, late and long-term effects of cancer and treatment, and the interplay of these factors with daily function and general health. For physicians, survivorship care plans can be a tool for coordinating the surveillance, intervention, and prevention of these key patient concerns. Though much of the research in cancer survivorship to date has focused on surveillance for recurrent disease, many national guidelines differ in their conclusions about the frequency and timing of follow-up tests. Most CRC guidelines refer only briefly to the management of side effects, despite reports that many patients have a range of ongoing physiological, psychosocial, and functional needs. Guidance for surveillance and intervention is often limited by a small number of heterogeneous trials conducted in this patient group. However, recently released survivorship guidelines emphasize the potential for the effectiveness of secondary prevention strategies, such as physical activity, to improve patient outcomes. There is also emerging evidence for the role of primary care providers and nurse coordinated care to support the transition and increase the cost-effectiveness of follow-up. The shift in focus from recurrence alone to the assessment and management of a range of survivorship issues will be important for ensuring that this growing group of patients achieves optimal outcomes. Keywords: survivorship care, surveillance, secondary prevention, clinical practice guidelines

Mikaela L Jorgensen,1,2 Jane M Young,1,2 Michael J Solomon1,31Surgical Outcomes Research Centre (SOuRCe), Sydney School of Public Health, University of Sydney and Sydney Local Health District, NSW, Australia; 2Cancer Epidemiology and Services Research (CESR), Sydney School of Public Health, University of Sydney, NSW, Australia; 3Discipline of Surgery, University of Sydney, NSW, AustraliaPurpose: Older colorectal cancer patients are significantly less likely than younger patients to receive guideline-recommended adjuvant chemotherapy. Previous research has indicated that patient refusal of treatment is a contributing factor. This study aimed to identify potential barriers to adjuvant chemotherapy use in older patients by examining the associations between patient age, factors influencing chemotherapy treatment decisions, and preferences for information and decision-making involvement.Patients and methods: Sixty-eight patients who underwent surgery for colorectal cancer in Sydney, Australia, within the previous 24 months completed a self-administered survey.Results: Fear of dying, health status, age, quality of life, and understanding treatment procedures and effects were significantly more important to older patients (aged ≥65 years) than younger patients in deciding whether to accept chemotherapy (all P < 0.05). Reducing the risk of cancer returning and physician trust were important factors for all patients. Practical barriers such as traveling for treatment and cost were rated lowest. Older patients preferred less information and involvement in treatment decision making than younger patients. However, 60% of the older group wanted detailed information about chemotherapy, and 83% wanted some involvement in decision making. Those preferring less information and involvement still rated many factors as important in their decision making, including understanding treatment procedures and effects.Conclusion: A range of factors appears to influence patients' chemotherapy decision making, including, but not limited to, survival benefits and treatment toxicity. For older patients, balancing the risks and benefits of treatment may be made more complex by the impact of emotional motivators, greater health concerns, and conflicts between their need for understanding and their information and decision-making preferences. Through greater understanding of perceived barriers to treatment and unique motivators for treatment choice, physicians may be better able to support older patients to make informed decisions about their care.Keywords: preferences, views, decision making, adjuvant therapy, older, elderly

Background: Although pain may persist for patients who undergo pelvic exenteration for treatment of locally recurrent rectal cancer, studies exploring patient experience of postoperative pain and its management remains limited., Objective: This study aimed to explore patient experiences of postoperative chronic pain and management following pelvic exenteration., Design: Qualitative cohort study of patients who have undergone pelvic exenteration for locally recurrent rectal cancer., Settings: The study was conducted through one-on-one semi-structured telephone interviews., Patients: Seventeen patients with locally recurrent rectal cancer who underwent pelvic exenteration between January 2018 and December 2020 were included., Main Outcome Measures: Semi-structured interviews explored participants' experiences of pain including its impact on life and management strategies at six and twelve months following exenteration. Interview transcripts were analyzed by two researchers using inductive thematic analysis., Results: Participant experiences of pain following exenteration are reflected by three themes identified: 1) adapting to long-term consequences of pelvic exenteration including pain, 2) reluctance to take pain medications, 3) engaging multidisciplinary care team is essential to post-pelvic exenteration chronic pain management. Several participants reported ongoing intermittent pain following surgery that significantly affected various aspects of their lives. This prompted participants to adapt their lifestyle and explore alternative pain relief methods as some were hesitant to rely on analgesics., Limitations: The small sample size from a single center whereby all patients underwent curative pelvic exenteration for lower recurrent rectal cancer with none undergoing the procedure for palliation limits the generalizability of the results of this study., Conclusions: While chronic pain following pelvic exenteration for locally recurrent rectal cancer interferes with patient's postoperative quality of life, analgesia use was influenced by pain habituation and fear of dependence on pain medications. Our findings emphasize the further need to investigate a multidisciplinary approach, including non-pharmacological methods, for optimization of pain outcomes following pelvic exenteration. See Video Abstract., Competing Interests: Financial Disclosures: All authors declare no conflicts of interests of competing interests. The Human Research Ethics Committee (RPAH Zone) of the Sydney Local Health District granted ethics approval for this project (Protocol Number X21-0489)., (Copyright © The ASCRS 2024.)

Background: Postoperative morbidity in patients undergoing curative colorectal cancer surgery is high. Prehabilitation has been suggested to reduce postoperative morbidity, however its effectiveness is still lacking., Objective: The aim of this study was to investigate the effectiveness of prehabilitation in reducing postoperative morbidity and length of hospital stay in patients undergoing colorectal cancer surgery., Methods: A comprehensive electronic search was conducted in the CINAHL, Cochrane Library, Medline, PsychINFO, AMED, and Embase databases from inception to April 2023. Randomised controlled trials testing the effectiveness of prehabilitation, including exercise, nutrition, and/or psychological interventions, compared with usual care in patients undergoing colorectal cancer surgery were included. Two independent review authors extracted relevant information and assessed the risk of bias. Random-effect meta-analyses were used to pool outcomes, and the quality of evidence was assessed using Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) guidelines., Results: A total of 23 trials were identified (N = 2475 patients), including multimodal (3 trials), exercise (3 trials), nutrition (16 trials), and psychological (1 trial) prehabilitation. There was moderate-quality evidence that preoperative nutrition significantly reduced postoperative infectious complications (relative risk 0.65, 95% confidence interval [CI] 0.45-0.94) and low-quality evidence on reducing the length of hospital stay (mean difference 0.87, 95% CI 0.17-1.58) compared with control. A single trial demonstrated an effect of multimodal prehabilitation on postoperative complication., Conclusion: Nutrition prehabilitation was effective in reducing infectious complications and length of hospital stay. Whether other multimodal, exercise, and psychological prehabilitation modalities improve postoperative outcomes after colorectal cancer surgery is uncertain as the current quality of evidence is low., Protocol Registration: Open Science Framework ( https://doi.org/10.17605/OSF.IO/VW72N )., (© 2024. The Author(s).)

Competing Interests: Conflicts of interest and disclosures: none declared

Preoperative assessment of functional capacity with the six-minute walk test (6MWT) allows for estimation of surgical risk and targeted triage to prehabilitation services. Patient with abdominal and pelvic cancers have worse preoperative function compared with the general population. However, six-minute walk distance (6MWD) reference values from cancer patients are unknown, which limits the interpretation of 6MWT in this population. This study aimed to establish an explanatory reference value model for preoperative 6MWD in patients with abdominal or pelvic cancers undergoing elective surgery. Adult patients undergoing surgery for abdominal or pelvic cancers at major international hospitals were included. The 6MWT was assessed before surgery using a standardised protocol. Anthropometric data including age, sex, height, weight and body mass index (BMI) were collected and included in multiple linear regression analysis to model preoperative 6MWD. A total of 742 patients were included. Age, height and BMI were correlated with 6MWD. Six regression models were estimated, including two from the entire cohort, two from the subset of males and two from the subset of females. A sex-neutral model was the most representative, explaining 15% of the variance in 6MWD (6MWD = 761.00-3.00 * Age (years) -2.86 * BMI (kg/m 2 ) - 48.09 * Sex (M1, F2)). The explored regression models, using anthropometric variables, poorly explained the variance between measured and modelled 6MWD, which suggests that these models have no clinical utility in the cancer population. Consideration of additional, non-anthropometric variables may improve regression modelling of preoperative 6MWD in patients in abdominal and pelvic cancers., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: The evidence on the effectiveness of prehabilitation in patients undergoing bladder cancer surgery remains lacking. Thus, the aim of this study is to determine the effectiveness of prehabilitation on reducing postoperative morbidity and length of hospital stay in patients undergoing bladder cancer surgery., Materials and Methods: This systematic review included randomized controlled trials investigating the effect of prehabilitation on postoperative outcomes in patients undergoing bladder cancer surgery. A comprehensive search was conducted, with two reviewers independently screening articles and extracting data. The Cochrane Collaboration's tool was used to assess risk of bias, and GRADE to rate the quality of evidence. When possible, a random effects meta-analysis was conducted. Estimates were presented as risk ratios or mean differences with their 95% confidence intervals., Results: Of the 2764 articles identified, five trials comprising 282 patients met the eligibility criteria. Prehabilitation modalities included preoperative exercise (3), preoperative nutrition (1), and multimodal (1). The mean age of patients ranged from 66.0 to 72.1 years. All included trials presented some or high risk of bias. Pooled analyses according to the different prehabilitation modalities demonstrated low to very low quality of evidence of no effect on postoperative complications and length of hospital stay., Conclusion: This study revealed a small number of trials investigating the effectiveness of prehabilitation on patients undergoing bladder cancer surgery. Whether prehabilitation, including preoperative exercise, nutrition and multimodal interventions reduce postoperative morbidity and length of hospital stay following bladder cancer surgery is uncertain, as the quality of evidence is very low.

Background: Total (procto)colectomy is indicated in 15%-20% of ulcerative colitis(UC) patients during their disease course. Reconstruction options to avoid a permanent ileostomy include an ileoanal pouch anastomosis (IPAA) or ileorectal anastomosis (IRA). This study aimed to investigate reconstruction rates using Australian-based population-level data, and factors influencing reconstruction., Methods: A retrospective data linkage study of the NSW population over a 19-year period was performed. Patients with UC who underwent total (procto)colectomy with a minimum of 1-year follow up were included. The main outcome was reconstruction with either IPAA or IRA. The influence of hospital and patient factors on reconstruction rates was assessed by Cox regression., Results: Overall, 1047 patients underwent a (procto)colectomy for UC (mean age 45.9 years [SD ± 18.3], 640 [61.1%] male). The 5-year reconstruction rate was 55% (IPAA 89%). Advanced age, emergent colectomy, higher comorbidity burden, and geographical remoteness were significantly associated with lower reconstruction rates. A lower reconstruction rate was also observed in the most recent time-period (2014-2019) (aHR 0.68[95% CI 0.54-0.86]), and where index (procto)colectomy was performed in low-volume (<1 pouch/year) pouch hospitals (aHR 0.60 [95% CI 0.43-0.82])., Conclusions: NSW Australia has the highest reported rate of reconstruction following UC (procto)colectomy globally. However, rates reduced in the most recent time-period. There was variation in reconstruction rates across centres, with primary and overall reconstruction rates proportionate to hospital pouch volume. Reconstruction rates were also lower for patients living outside major cities. To ensure equitable opportunities for reconstruction, patients being considered for IBD pouch surgery should be centralized to a limited number of specialist pouch centres., (© 2024 The Authors. ANZ Journal of Surgery published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Surgeons.)

Introduction: Stage IV colorectal cancer is a highly challenging condition to treat, with 5-year survival rates of 13% in Australia, improving to 40% for those patients with locally recurrent rectal cancer who are suitable for total neoadjuvant therapy and pelvic exenterative surgery. This study reports a unique case of a patient with Stage IV locally recurrent rectal cancer (LRRC), who designed and implemented a holistic integrative oncology intervention., Case Presentation: The patient was 59-years-old when diagnosed with Stage IV locally recurrent rectal cancer, and referred to a highly specialised centre for colorectal cancer care at a tertiary teaching hospital in Sydney, Australia. Treatment included chemo/radiotherapy, liver resection and posterior pelvic exenteration surgery. The patient's background as a health researcher and clinician optimised her ability to design and implement an integrative oncology model of care, including yoga, mindfulness, Buddhist meditation and study, social connection, exercise, psychotherapeutic and nutritional support. This paper describes these mind-body practices and lifestyle modifications and outlines her experiences and outcomes at each stage of her extensive and radical treatment., Conclusion: This case provides a unique perspective into how the integration of mind-body practices and lifestyle modifications with conventional treatment can support those living with colorectal cancer., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Aim: Total (procto)colectomy for ulcerative colitis (UC) is associated with significant morbidity, which is increased in the emergency setting. This study aimed to evaluate the outcomes following total (procto)colectomies at a population level within New South Wales (NSW), Australia, and identify case mix and hospital factors associated with these outcomes., Methods: A retrospective data linkage study of patients undergoing total (procto)colectomy for UC in NSW over a 19-year period (2001-2020) was performed. The primary outcome was 90-day mortality. The influence of hospital level factors (including annual volume) and patient demographic variables on outcomes was assessed using logistic regression. Temporal trends in annual volume and evidence for centralization were assessed., Results: In all, 1418 patients (mean 47.0 years [SD 18.7], 58.7% male) underwent total (procto)colectomy during the study period. The overall 90-day mortality rate was 3.2% (emergency 8.6% and elective 0.8%). After adjusting for confounding, increasing age at total (procto)colectomy, higher comorbidity burden, public health insurance (Medicare) status, emergency operation and living outside a major city were significantly associated with increased mortality. Hospital volume was significantly associated with mortality at a univariate level, but this did not persist on multivariate modelling., Conclusions: Outcomes of UC patients undergoing total (procto)colectomy in NSW Australia are comparable to international experience. Whilst higher mortality rates are observed in low volume and public hospitals, this appears attributable to case mix and acuity rather than surgical volume alone. However, as inflammatory bowel disease surgery is not centralized in Australia, only one NSW hospital performed >10 UC total (procto)colectomies annually. Variation in mortality according to insurance status and across regional/remote areas may indicate inequality in the availability of specialist inflammatory bowel disease treatment, which warrants further research., (© 2024 The Author(s). Colorectal Disease published by John Wiley & Sons Ltd on behalf of Association of Coloproctology of Great Britain and Ireland.)

Objective: Telehealth has been proposed as a safe and effective alternative to in-person care for rheumatoid arthritis (RA). The purpose of this study was to evaluate factors associated with telehealth appropriateness in outpatient RA encounters., Methods: A prospective cohort study (January 1, 2021, to August 31, 2021) was conducted using electronic health record data from outpatient RA encounters in a single academic rheumatology practice. Rheumatology providers rated the telehealth appropriateness of their own encounters using the Encounter Appropriateness Score for You (EASY) immediately following each encounter. Robust Poisson regression with generalized estimating equations modeling was used to evaluate the association of telehealth appropriateness with patient demographics, RA clinical characteristics, comorbid noninflammatory causes of joint pain, previous and current encounter characteristics, and provider characteristics., Results: During the study period, 1823 outpatient encounters with 1177 unique patients with RA received an EASY score from 25 rheumatology providers. In the final multivariate model, factors associated with increased telehealth appropriateness included higher average provider preference for telehealth in prior encounters (relative risk [RR] 1.26, 95% CI 1.21-1.31), telehealth as the current encounter modality (RR 2.27, 95% CI 1.95-2.64), and increased patient age (RR 1.05, 95% CI 1.01-1.09). Factors associated with decreased telehealth appropriateness included moderate (RR 0.81, 95% CI 0.68-0.96) and high (RR 0.57, 95% CI 0.46-0.70) RA disease activity and if the previous encounters were conducted by telehealth (RR 0.83, 95% CI 0.73-0.95)., Conclusion: In this study, telehealth appropriateness was most associated with provider preference, the current and previous encounter modality, and RA disease activity. Other factors like patient demographics, RA medications, and comorbid noninflammatory causes of joint pain were not associated with telehealth appropriateness., (Copyright © 2024 by the Journal of Rheumatology.)

Objective In Australia, there is little evidence exploring why higher degrees by research (HDRs) are undertaken by surgeons. This study aims to describe the attitudes and experiences of surgical trainees and surgeons towards HDRs. Methods A 23-question cross-sectional survey of surgical trainees and consultant surgeons from three Australian public hospitals was undertaken between August and December 2022. Data were analysed according to stage of career and HDR status and assessed using chi-squared test, with P <0.05 considered significant. Results Out of 270 participants, 72 (27%) completed the survey including 30 (42%) trainees and 42 (58%) consultants. Overall, 43 (60%) participants had completed or were undertaking a HDR, which was similar between trainees (n =18) and consultants (N =25; P =0.968). A HDR was associated with more publications (P <0.5). Respondents with a HDR were more likely to have a salaried academic position (50%) than those without (15%). There was no significant difference in academic appointments based on HDR attainment (P =0.192). For surgical trainees, 93% rated the strengthening of resumes as the primary driver, compared with only 60% of consultants. For consultants, academic career aspirations and research interests were ranked the highest at 64% equally. Lack of time and competing nature of surgical training were equally ranked among all as the key barriers to completing a HDR. Conclusions These results provide insight into the academic pursuits of surgeons with an understanding of the role HDRs play, including the different drivers for Masters and Doctorates. This is important for supporting future surgeons who seek to pursue research.

Background: A key component of preoperative preparation for pelvic exenteration surgery is the development of an operative plan in a multidisciplinary setting based on the extent of local tumor invasion on preoperative imaging. Changes to the extent of resection or operative plan may occur intraoperatively based on intraoperative findings., Objective: To report the frequency and extent of intraoperative deviation from the planned extent of resection during pelvic exenteration for locally recurrent rectal cancer and determine whether this resulted in a more or less radical resection., Design: Retrospective observational study., Settings: A high-volume pelvic exenteration center., Patients: Patients who underwent pelvic exenteration for locally recurrent rectal cancer between January 2015 and December 2020., Main Outcome Measures: Frequency and extent of intraoperative deviation from the planned extent of resection, R0 resection rate., Results: One hundred thirty-six patients underwent pelvic exenteration for locally recurrent rectal cancer, of whom 110 (81%) had R0 resection margins. Twelve patients were excluded because of missing information, and 49 patients (40%) had a change to the operative plan. Operative changes were major in 30 patients (61%), more radical in 40 patients (82%), and margin relevant in 24 patients (49%). In patients in whom there was a change to the operative plan and R0 resection was achieved, the median distance to a relevant margin was 2.5 mm (range, 0.1-10 mm). Of 8 patients with a change in operative plan and R1 resection, 3 were margin relevant, of whom all were considered major, and 2 were more radical and 1 was less radical., Limitations: Generalizability outside of specialist units may be limited., Conclusions: Intraoperative changes to the planned extent of resection occur commonly and most often result in an unanticipated major or more radical resection. Such changes may contribute to high rates of R0 resection margins in specialist pelvic exenteration units that use an ultraradical approach in these patients. See Video Abstract ., Impacto De La Toma De Decisiones Intraoperatoria Sobre El Estado Del Margen Patolgico En Pacientes Sometidos a Exenteracin Plvica Por Recurrencia Local En Cncer De Recto: ANTECEDENTES:Un componente clave de la preparación preoperatoria para exenteración pélvica es el desarrollo de un plan quirúrgico en un entorno multidisciplinario, basado en el grado de invasión tumoral local en las imágenes preoperatorias. Es posible que se produzcan cambios intraoperatorios en la extensión de la resección o en el plan quirúrgico según los hallazgos intraoperatorios.OBJETIVO:Informar la frecuencia y la extensión de la desviación intraoperatoria de la extensión planificada de la resección durante la exenteración pélvica para el cáncer de recto localmente recurrente, y si esto resultó en una resección más o menos radical.DISEÑO:Estudio observacional retrospectivo.ESCENARIO:Un centro de exenteración pélvica de alto volumen.PACIENTES:Pacientes sometidos a exenteración pélvica por cáncer de recto localmente recurrente entre enero de 2015 y diciembre de 2020.PRINCIPALES MEDIDAS DE RESULTADO:Frecuencia y extensión de desviación intraoperatoria de la extensión planeada de resección, tasa de resección R0.RESULTADOS:136 pacientes fueron sometidos a exenteración pélvica por cáncer de recto localmente recurrente, de los cuales 110 (81%) tuvieron márgenes de resección R0. 12 pacientes fueron excluidos por falta de información y 49 pacientes (40%) tuvieron un cambio en el plan quirúrgico. Los cambios operatorios fueron mayores en 30 pacientes (61%), más radicales en 40 pacientes (82%) y con relevancia sobre márgenes en 24 pacientes (49%). En los pacientes en los que hubo un cambio en el plan quirúrgico y se logró la resección R0, la distancia mediana hasta un margen relevante fue de 2.5 mm (rango 0.1-10 mm). De ocho pacientes con un cambio en el plan quirúrgico y resección R1, tres tuvieron relevancia sobre márgenes de los cuales todos se consideraron mayores, dos fueron más radicales y uno fue menos radical.LIMITACIONES:La generalización fuera de las unidades especializadas puede ser limitada.CONCLUSIONES:Los cambios intraoperatorios en la extensión planificada de la resección ocurren comúnmente y con mayor frecuencia resultan en una resección mayor imprevista y más radical. Dichos cambios pueden contribuir a altas tasas de márgenes de resección R0 en unidades especializadas en EP que emplean un enfoque ultrarradical en estos pacientes. (Traducción-Dr. Jorge Silva Velazco )., (Copyright © The ASCRS 2024.)

The Anaphase-Promoting Complex/Cyclosome (APC/C) is a ubiquitin ligase that promotes the ubiquitination and subsequent degradation of numerous cell cycle regulators during mitosis and in G1. Proteins are recruited to the APC/C by activator proteins such as Cdh1. During the cell cycle, Cdh1 is subject to precise regulation so that substrates are not degraded prematurely. We have explored the regulation of Cdh1 during the developmental transition into meiosis and sporulation in the budding yeast S. cerevisiae . Transition to sporulation medium triggers the degradation of Cdh1. Cdh1 degradation is mediated by the APC/C itself in a " trans " mechanism in which one molecule of Cdh1 recruits a second molecule of Cdh1 to the APC/C for ubiquitination. Degradation requires an intact glucose-sensing SNF1 protein kinase complex (orthologous to the mammalian AMPK nutritional sensor), which directly phosphorylates Cdh1 on Ser-200 within an unstructured N-terminal region. In the absence of phosphorylation, expression of a Cdh1-S200A mutant is fully stabilized, leading to chromosome instability and loss of viability. We hypothesize that Cdh1 degradation is necessary for the preservation of cell cycle regulators and chromosome cohesion proteins between the reductional and equational meiotic divisions, which occur without the intervening Gap or S phases found in mitotic cell cycles.

Background: Whilst both mental illness comorbidity and the delivery of emergency surgery are commonplace in Australia, there is little evidence investigating any link between them. As such, this study examines the emergency surgical outcomes for patients with mental illness compared to other surgical patients within the Australian public surgical system., Methods: Retrospective cohort study involving adult emergency and elective surgical patients treated at three public hospitals in Sydney, Australia between 2018 and 2019. Patients were identified using ICD-10 diagnosis codes, and grouped by those with decompensated mental illness, chronic depression, or those without mental illness. Outcome measures included those within the emergency department (ED), along with in-hospital mortality and surgical outcomes., Results: Of 48 338 total patients, 31 890 (66.0%) had elective and 16 448 (34.0%) had emergency surgery. For patients with decompensated mental illness, only 228 (0.7%) had elective whilst 425 (2.6%) had emergency surgery. Their outcomes for this surgery type included being triaged significantly higher (Cat 1 or 2, 34% vs. 15%) and longer ED stays (8.3 vs. 6.6 h). They also had significantly more post-operative complications (26% vs. 8%) and total days in hospital (33.8 vs. 8.5 days). There was no significant difference for in-hospital mortality., Conclusion: Patients with mental illness are significantly more likely to have emergency surgery including presenting to the ED with more acute physical illness and to experience worse surgical outcomes compared to other surgical patients for every measure analyzed except mortality. There is considerable opportunity to further investigate how these differences might be improved., (© 2024 The Authors. ANZ Journal of Surgery published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Surgeons.)

Locally advanced or recurrent prostate cancer which invades adjacent pelvic organs, bone or other soft tissue structures is a rare situation. This study aimed to report the outcomes of ten consecutive patients who underwent total pelvic exenteration for prostate cancer at a high-volume specialist centre. Two patients had locally advanced primary tumours, while eight had locally recurrent prostate cancer. Median operating time, blood loss, ICU stay, and hospital stay was 12.2 h (range 9.6-13.8), 2500 ml (500-3000), 4.5 days (2-7) and 36 days (21-78), respectively. There was no inpatient, 30-day, or 90-day mortality. Six patients developed a Clavien-Dindo III complication. R0 resection was achieved in eight patients. Median follow up was 16 months (range 2-77). At last follow up, five patients were alive without disease. These findings suggest that pelvic exenteration for locally advanced and recurrent prostate cancer is safe and represents a potentially curative treatment option for highly selected patients., Competing Interests: Declaration of competing interest All the authors have made a significant contribution to this manuscript, have seen and approved the final manuscript, and have agreed to its submission to the EJSO. There are no conflicts of interest to declare., (© 2024 Published by Elsevier Ltd.)

Aim: Early-onset colorectal cancer (EOCRC) patients are more likely to have advanced disease and undergo more aggressive treatment modalities. However, current literature investigating the health-related quality of life (HRQoL) of EOCRC patients is scarce. This study aimed to determine the HRQoL of an Australian cohort of EOCRC patients including a subset who underwent pelvic exenteration (PE) or cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC)., Method: A cross-sectional study of EOCRC patients treated at the Royal Prince Alfred Hospital, Sydney Australia was performed. Patients were divided into groups based on the time interval from their index operation: ≤2 years and >2 years. HRQoL was evaluated using the SF-36v2 questionnaire., Results: A total of 50 patients were included. For patients ≤2 years from surgery, the median physical component summary (PCS) and mental health component summary (MCS) scores were 53.3 (36.4-58.9) and 47.3 (37.5-55.7). In the >2 years group, the median PCS and MCS scores were 50.6 (43.3-57.7) and 50.2 (39.04-56.2), respectively. Stage I (vs. stage II) disease and emergency (vs. elective) surgery conferred poorer PCS scores in patients ≤2 years from surgery. No other variables impacted PCS or MCS scores in EOCRC patients in either group., Conclusions: HRQoL of EOCRC patients was equivocal to the Australian population. Having an earlier stage of diagnosis and emergency index operation was associated with poorer levels of physical functioning in patients ≤2 years from surgery. However, because of the limitations of this study, these findings require validation in future large-scale prospective research., (© 2024 The Author(s). Colorectal Disease published by John Wiley & Sons Ltd on behalf of Association of Coloproctology of Great Britain and Ireland.)

Background: Extended radical resection is often the only chance of cure for locally recurrent rectal cancer. Recurrence in the posterior compartment often necessitates en bloc sacrectomy as part of pelvic exenteration to obtain clear resection margins and provide survival benefit., Objective: To compare oncological outcomes, morbidity, and quality-of-life outcomes following pelvic exenteration with and without en bloc sacrectomy for recurrent rectal cancer., Design: Comparative cohort study with retrospective analysis of prospectively collected data., Setting: This study was conducted at a high-volume pelvic exenteration center., Patients: Patients who underwent pelvic exenteration for locally recurrent rectal cancer between 1994 and 2022., Main Outcome Measures: Overall survival, postoperative morbidity, R0 resection margin, and quality-of-life outcomes., Results: Of 965 patients, 305 (31.6%) underwent pelvic exenteration for locally recurrent rectal cancer. Among these patients, 64.3% were men and the median age was 62 years (range, 29-86). One hundred eighty-five patients (60.7%) underwent en bloc sacrectomy, 65 (35.1%) underwent high transection, and 119 (64.3%) had sacrectomy below S2. R0 resection was achieved in 80% of patients with sacrectomy and 72.5% of patients without sacrectomy. Sacrectomy patients experienced more postoperative complications without increased mortality. The median overall survival was 52 months; median survival was 47 months with sacrectomy and 73 months without ( p  = 0.059). Quality-of-life scores were not significantly different across physical component ( p  = 0.346), mental component ( p  = 0.787), or Functional Assessment of Cancer Therapy-Colorectal ( p  = 0.679) scores at 24-month follow-up., Limitations: The generalizability of these findings may be limited outside of subspecialist exenteration units. Selection bias exists in a retrospective analysis., Conclusions: Patients undergoing pelvic exenteration with and without en bloc sacrectomy for locally recurrent rectal cancer experience similar rates of R0 resection, survival, and quality-of-life outcomes. As R0 remains the most important predictor of survival, the requirement of sacral resection should prompt referral to a subspecialist center that performs sacrectomy routinely. See Video Abstract ., Resultados Despus De La Exenteracin Plvica Para El Cncer De Recto Con Recurrencia Local, Con Y Sin Sacrectoma En Bloque: ANTECEDENTES:La resección radical ampliada es generalmente la única posibilidad de curación para el cáncer de recto con recurrencia local. La recurrencia en el compartimento posterior generalmente requiere sacrectomía en bloque como parte de la exenteración pélvica para obtener márgenes de resección claros y proporcionar un beneficio de supervivencia.OBJETIVO:Comparar los resultados oncológicos, de morbilidad y de calidad de vida después de la exenteración pélvica con y sin sacrectomía en bloque para el cáncer de recto recurrente.DISEÑO:Estudio de cohorte comparativo con análisis retrospectivo de datos recopilados prospectivamente.AMBIENTE AJUSTE:Estudio realizado en un centro de exenteración pélvica de alto volumen.PACIENTES:Aquellos sometidos a exenteración pélvica por cáncer de recto con recurrencia local entre 1994 y 2022.PRINCIPALES MEDIDAS DE RESULTADO:Supervivencia general, morbilidad posoperatoria, margen de resección R0 y resultados de calidad de vida.RESULTADOS:305 (31,6%) de 965 pacientes se sometieron a exenteración pélvica por cáncer de recto con recurrencia local. El 64,3% de los pacientes eran hombres con una mediana de edad de 62 años (rango 29-86). 185 pacientes (60,7%) fueron sometidos a sacrectomía en bloque, 65 (35,1%) fueron sometidos a transección alta, 119 (64,3%) tuvieron sacrectomía por debajo de S2. La resección R0 se logró en el 80% de los pacientes con sacrectomía y en el 72,5% sin ella. Los pacientes de sacrectomía experimentaron más complicaciones postoperatorias sin aumento de la mortalidad. La mediana de supervivencia global fue de 52 meses, 47 meses con sacrectomía y 73 meses sin sacrectomía ( p = 0,059). Las puntuaciones de calidad de vida no fueron significativamente diferentes entre las puntuaciones del componente físico ( p = 0,346), componente mental ( p = 0,787) o la evaluación funcional de la terapia contra el cáncer - colorrectal ( p = 0,679) a los 24 meses de seguimiento.LIMITACIONES:La generalización de estos hallazgos puede estar limitada fuera de las unidades de exenteración de subespecialistas. Existe un sesgo de selección en un análisis retrospectivo.CONCLUSIONES:Los pacientes sometidos a exenteración pélvica con y sin sacrectomía en bloque por cáncer de recto con recurrencia local experimentan tasas similares de resección R0, supervivencia y resultados de calidad de vida. Como R0 sigue siendo el predictor más importante de supervivencia, la necesidad de resección sacra debe provocar la derivación a un centro subespecialista que realice sacrectomía de forma rutinaria. (Traducción-Dr. Fidel Ruiz Healy )., (Copyright © The ASCRS 2024.)

Objective: To establish globally applicable benchmark outcomes for pelvic exenteration (PE) in patients with locally advanced primary (LARC) and recurrent rectal cancer (LRRC), using outcomes achieved at highly specialised centres., Background Data: PE is established as the standard of care for selected patients with LARC and LRRC. There are currently no available benchmarks against which surgical performance in PE can be compared for audit and quality improvement., Methods: This international multicentre retrospective cohort study included patients undergoing PE for LARC or LRRC at 16 highly experienced centres between 2018 and 2023. Ten outcome benchmarks were established in a lower-risk subgroup. Benchmarks were defined by the 75th percentile of the results achieved at the individual centres., Results: 763 patients underwent PE, of which 464 patients (61%) had LARC and 299 (39%) had LRRC. 544 patients (71%) who met predefined lower risk criteria formed the benchmark cohort. For LARC patients, the calculated benchmark threshold for major complication rate was ≤44%; comprehensive complication index (CCI): ≤30.2; 30-day mortality rate: 0%; 90-day mortality rate: ≤4.3%; R0 resection rate: ≥79%. For LRRC patients, the calculated benchmark threshold for major complication rate was ≤53%; CCI: ≤34.1; 30-day mortality rate: 0%; 90-day mortality rate: ≤6%; R0 resection rate: ≥77%., Conclusions: The reported benchmarks for PE in patients with LARC and LRRC represent the best available care for this patient group globally and can be used for rigorous assessment of surgical quality and to facilitate quality improvement initiatives at international exenteration centres., Competing Interests: Conflicts of interest and disclosures: Julio Garcia-Aguilar disclosures - Ethicon (Professional Services and Activities) and Intuitive Surgical Inc. Equity (Professional Services and Activities)., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Ileal pouch-anal anastomosis ('pouch surgery') provides a chance to avoid permanent ileostomy after proctocolectomy, but can be associated with poor outcomes. The relationship between hospital-level/surgeon factors (including volume) and outcomes after pouch surgery is of increasing interest given arguments for increasing centralization of these complex procedures. The aim of this systematic review was to appraise the literature describing the influence of hospital-level and surgeon factors on outcomes after pouch surgery for inflammatory bowel disease., Methods: A systematic review was performed of studies reporting outcomes after pouch surgery for inflammatory bowel disease. The MEDLINE (Ovid), Embase (Ovid), and Cochrane CENTRAL databases were searched (1978-2022). Data on outcomes, including mortality, morbidity, readmission, operative approach, reconstruction, postoperative parameters, and pouch-specific outcomes (failure), were extracted. Associations between hospital-level/surgeon factors and these outcomes were summarized. This systematic review was prospectively registered in PROSPERO, the international prospective register of systematic reviews (CRD42022352851)., Results: A total of 29 studies, describing 41 344 patients who underwent a pouch procedure, were included; 3 studies demonstrated higher rates of pouch failure in lower-volume centres, 4 studies demonstrated higher reconstruction rates in higher-volume centres, 2 studies reported an inverse association between annual hospital pouch volume and readmission rates, and 4 studies reported a significant association between complication rates and surgeon experience., Conclusion: This review summarizes the growing body of evidence that supports centralization of pouch surgery to specialist high-volume inflammatory bowel disease units. Centralization of this technically demanding surgery that requires dedicated perioperative medical and nursing support should facilitate improved patient outcomes and help train the next generation of pouch surgeons., (© The Author(s) 2024. Published by Oxford University Press on behalf of BJS Foundation Ltd. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Information on the course of quality of life after surgery for advanced cancers within the pelvis is important to guide patient decision-making; however, the current evidence is limited., Objective: To identify quality-of-life trajectory classes and their predictors after pelvic exenteration., Design: Prospective cohort study., Settings: Highly specialized quaternary pelvic exenteration referral center., Patients: Patients undergoing pelvic exenteration due to advanced/recurrent cancers within the pelvis between July 2008 and July 2022., Main Outcome Measures: Quality-of-life data included the 36-item Short-Form Survey (physical and mental component scores) and the Functional Assessment of Cancer Therapy-Colorectal instruments, which were collected at 11 distinct points from baseline to 5 years postoperatively. Predictors included patient characteristics and surgical outcomes. Latent class analysis was used to identify the likelihood of a better quality-of-life class, and logistic regression models were used to identify predictors of the identified classes., Results: The study included 565 participants. Two distinct quality-of-life trajectory classes were identified for the Physical Component Score (class 1: high stable and class 2: high decreasing). Three distinct classes were identified for the Mental Component Score (class 1: high increasing, class 2: moderate stable, and class 3: moderate decreasing) and for Functional Assessment of Cancer Therapy-Colorectal total score (class 1: high increasing, class 2: high decreasing, and class 3: low decreasing). Across the 3 quality-of-life domains, overall survival probabilities were also higher in class 1 ( p < 0.0001). Age, repeat exenteration, neoadjuvant therapy, surgical margin, length of operation, and hospital stay were significant predictors of quality-of-life classes., Limitations: This study was conducted at a single highly specialized quaternary pelvic exenteration referral center, and findings may not apply to other centers., Conclusions: This study demonstrates that quality of life after pelvic exenteration diverges into distinct trajectories, with most patients reporting an optimal course. See Video Abstract ., Trayectorias En La Calidad De Vida Despus De Exenteracin Plvica Anlisis De Crecimiento De Clases Latentes: ANTECEDENTES:La información sobre la evolución en la calidad de vida después de cirugía en cánceres avanzados situados en la pelvis es importante para guiar la toma de decisiones sobre el paciente; sin embargo, la evidencia actual es muy limitada.OBJETIVO:Identificar las clases de trayectorias en la calidad de vida y sus factores pronóstico después de la exenteración pélvica.DISEÑO:Estudio de cohortes prospectivo.AJUSTES:Centro de referencia altamente especializado en la exenteración pélvica cuaternaria.PACIENTES:Todos aquellos sometidos a exenteración pélvica por cáncer avanzados/recurrentes situados en la pelvis entre Julio de 2008 y Julio de 2022.PRINCIPALES MEDIDAS DE RESULTADO:Los datos sobre la calidad de vida incluyeron el Cuestionario de Salud SF-36 (puntuaciones de componentes físicos y mentales) y la evaluación funcional entre la terapia del cáncer/-herramientas colorrectales, recopilados en 11 puntos distintos desde el diagnóstico hasta los 5 años después de la operación.Los predictores incluyeron las características de los pacientes y los resultados quirúrgicos. Se utilizó el análisis de clases latentes para identificar la probabilidad de una mejor calidad de vida y se utilizaron modelos de regresión logística para identificar predictores de las clases identificadas.RESULTADOS:El estudio incluyó a 565 participantes. Se identificaron dos clases distintas de trayectorias de calidad de vida para la puntuación del componente físico (clase 1: alta estable y clase 2: alta decreciente), se identificaron tres clases distintas para la puntuación del componente mental (clase 1: alta creciente; clase 2: moderadamente estable; y clase 3: moderada disminución) y para la evaluación funcional de la terapia contra el cáncer-puntuación total colorrectal (clase 1: aumento alto; clase 2: disminución alta; y clase 3: disminución baja). En los tres dominios de calidad de vida, las probabilidades de supervivencia general también fueron mayores en las clases 1 (p <0,0001). La edad, las exenteraciones pélvicas repetidas, la terapia neoadyuvante, el margen quirúrgico, la duración de la operación y la estadía hospitalaria fueron predictores significativos en las clases de calidad de vida.LIMITACIONES:El presente estudio fué realizado en un único centro de referencia altamente especializado en exenteración pélvica cuaternaria y es posible que los hallazgos no se apliquen a otros centros.CONCLUSIONES:Demostramos con nuestro estudio que la calidad de vida después de la exenteración pélvica diverge en trayectorias distintas, y que la mayoría de los pacientes nos reportaron de una évolución óptima. (Traducción-Dr. Xavier Delgadillo )., (Copyright © The ASCRS 2024.)

Objective: To compare perioperative morbidity, functional and quality-of-life (QoL) outcomes in patients with partial cystectomy vs radical cystectomy as part of pelvic exenteration., Patients and Methods: Retrospective analysis of a prospectively maintained database of pelvic exenteration patients (1998-2021) was conducted in a single centre. Study outcomes included postoperative complications, quality-of-life, functional and stoma-related outcomes. The 36-item Short-Form Health Survey Physical and Mental Health Components, Functional Assessment of Cancer Therapy-Colorectal questionnaires and Distress Thermometer were available pre- and postoperatively. QoL outcomes were compared at the various time points. Stoma embarrassment and care scores were compared between patients with a colostomy, urostomy, and both., Results: Urological complications were similar between both groups, but patients with partial cystectomy experienced less wound-related complications. Overall, 34/81 (42%) partial cystectomy patients reported one or more long-term voiding complication (i.e., incontinence [17 patients], frequency [six], retention [three], high post-voiding residuals [10], permanent suprapubic catheter/indwelling catheter [14], recurrent urinary tract infection [nine], percutaneous nephrostomy [three], progression to urostomy [three]). The QoL improved following surgery in both the partial and radical cystectomy groups, differences between cohorts were not significant. Patients with two stomas reported higher embarrassment scores than patients with one stoma, although this did not result in more difficulties in stoma care., Conclusions: Partial cystectomy patients have fewer postoperative wound-related complications than radical cystectomy patients, but often experience long-term voiding issues. The QoL outcomes are similar for both cohorts, with significant improvement following surgery., (© 2024 The Authors. BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Background: This study describes surgical and quality of life outcomes in patients with peritoneal malignancy treated by cytoreductive surgery (CRS) alone compared with a subgroup treated with CRS and hyperthermic intraperitoneal chemotherapy (HIPEC)., Methods: Peritoneal malignancy patients undergoing surgery between 2017 and 2023 were included. The cohort was divided into patients treated by CRS and HIPEC and those treated by CRS without HIPEC (including CRS only or maximal tumour debulking (MTB)). Main outcomes included surgical outcomes, survival, and quality of life. Groups were compared using non-parametric tests and log-rank test was used to compare survival curves., Results: 403 had CRS and HIPEC, 25 CRS only and 15 MTB. CRS and HIPEC patients had a lower peritoneal carcinomatosis index (12.0 vs. 17.0 vs. 35.0; P < 0.001) and longer surgical operative time (9.3 vs. 8.3 vs. 5.2 h; P < 0.001), when compared to CRS only and MTB, respectively. No other significant difference between groups was observed., Conclusions: The optimal management of selected patients with resectable peritoneal malignancy incorporates a combined strategy of CRS and HIPEC. When HIPEC is not utilized, due to significant residual disease or comorbidity precluding safe delivery, CRS alone is associated with good outcomes. Hospital stay and complications are acceptable but not significantly different to the CRS and HIPEC group. CRS alone is a complex intervention requiring comparable resources with good outcomes. In view of our findings 'intention to treat' with CRS and HIPEC should be the basis for resource allocation and funding., (© 2024 The Authors. ANZ Journal of Surgery published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Surgeons.)

Importance: Extramammary Paget disease (EMPD) is a rare, highly recurrent cutaneous malignant neoplasm of unclear origin. EMPD arises most commonly on the vulvar and penoscrotal skin. It is not presently known how anatomic subtype of EMPD affects disease presentation and management., Objective: To compare demographic and tumor characteristics and treatment approaches for different EMPD subtypes. Recommendations for diagnosis and treatment are presented., Data Sources: MEDLINE, Embase, Web of Science Core Collection, and Cochrane Reviews CENTRAL from December 1, 1990, to October 24, 2022., Study Selection: Articles were excluded if they were not in English, reported fewer than 3 patients, did not specify information by anatomic subtype, or contained no case-level data. Metastatic cases on presentation were also excluded., Data Extraction and Synthesis: Abstracts of 1295 eligible articles were independently reviewed by 5 coauthors, and 135 articles retained. Reporting was in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines. The analysis was cunducted in August 2019 and updated in November 2022., Findings: Most vulvar EMPD cases were asymptomatic, and diagnosis was relatively delayed (mean, 25.1 months). Although most vulvar EMPD cases were intraepidermal (1247/1773 [70.3%]), radical surgeries were still performed in almost one-third of cases. Despite this aggressive surgical approach, 481 of 1423 (34%) recurred, commonly confined to the skin and mucosa (177/198 [89.4%]). By contrast, 152 of 1101 penoscrotal EMPD cases (14%) recurred, but more than one-third of these recurrences were regional or associated with distant metastases (54 of 152 [35.5%]). Perianal EMPD cases recurred in one-third of cases (74/218 [33.9%]), with one-third of these recurrences being regional or associated with distant metastasis (20 of 74 [27.0%]). Perianal EMPD also had the highest rate of invasive disease (50% of cases)., Conclusions and Relevance: The diagnosis and treatment of EMPD should differ based on anatomic subtypes. Considerations for updated practice may include less morbid treatments for vulvar EMPD, which is primarily epidermal, and close surveillance for local recurrence in vulvar EMPD and metastatic recurrence in perianal EMPD. Recurrences in penoscrotal subtype were less common, and selective surveillance in this subtype may be considered. Limitations of this study include the lack of replication cohorts and the exclusion of studies that did not stratify outcomes by anatomic subtype.

Background: Restorative proctocolectomy (RP) with ileal pouch-anal anastomosis (IPAA) remains the gold standard for the surgical management of patients with medically refractive mucosal ulcerative colitis. We aimed to identify functional and quality of life (QOL) outcomes in RP and IPAA surgery patients at our institution., Methods: A retrospective observational study was performed including all patients who had undergone RP and IPAA between August 1984 and November 2017 at Royal Prince Alfred Hospital (RPAH)., Results: 316 consecutive patients were identified, median age 39 (range 5 to 81) years. The median duration of disease was 60 (range 1 to 528) months. Ulcerative colitis was the main preoperative diagnosis with the main RP indication being failure of medical treatment. The median postoperative stay post-IPAA was 11 (range of 5 to 67) days. Pouchitis was the most common late complication (22.1%), bleeding pouch (3.5%) the earliest, with a 6.8% rate of symptomatic anastomotic leak. Visual analogue scale QOL measure (P-value <0.001), St Marks incontinence score (P-value = 0.001) and Cleveland clinic score (P-value = 0.002) all revealed significant improvement in functional outcomes and QOL., Conclusion: QOL and functional outcomes following RP with IPAA in patients at our institution are excellent and comparable to institutions with larger patient numbers., (© 2023 The Authors. ANZ Journal of Surgery published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Surgeons.)

Objective: This study aims to explore the factors associated with rheumatology providers' perceptions of telehealth utility in real-world telehealth encounters., Methods: From September 14, 2020 to January 31, 2021, 6 providers at an academic medical center rated their telehealth visits according to perceived utility in making treatment decisions using the following Telehealth Utility Score (TUS) (1 = very low utility to 5 = very high utility). Modified Poisson regression models were used to assess the association between TUS scores and encounter diagnoses, disease activity measures, and immunomodulatory therapy changes during the encounter., Results: A total of 481 telehealth encounters were examined, of which 191 (39.7%) were rated as "low telehealth utility" (TUS 1-3) and 290 (60.3%) were rated as "high telehealth utility" (TUS 4-5). Encounters with a diagnosis of inflammatory arthritis were significantly less likely to be rated as high telehealth utility (adjusted relative risk [aRR], 0.8061; p = 0.004), especially in those with a concurrent noninflammatory musculoskeletal diagnosis (aRR, 0.54; p = 0.006). Other factors significantly associated with low telehealth utility included higher disease activity according to current and prior RAPID3 scores (aRR, 0.87 and aRR, 0.89, respectively; p < 0.001) and provider global scores (aRR, 0.83; p < 0.001), as well as an increase in immunomodulatory therapy (aRR, 0.70; p = 0.015)., Conclusions: Provider perceptions of telehealth utility in real-world encounters are significantly associated with patient diagnoses, current and prior disease activity, and the need for changes in immunomodulatory therapy. These findings inform efforts to optimize the appropriate utilization of telehealth in rheumatology., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)