Citations

ABSTRACT Autoimmune pancreatitis (AIP) and pancreatic cancer share clinical and radiological features, making biopsy the only definitive way of differentiating them. Numerous reports in the literature describe the co-occurrence of AIP and pancreatic cancer either in a synchronous manner or metachronous manner raising the question of which condition predisposes to the other and whether a causal relationship exists between them. Studies suggest shared mechanisms, including K-ras mutations and tumor suppressor gene silencing. This case highlights the importance of long-term surveillance in AIP patients to monitor for malignancy.

Abstract Background and Aims Truncating variants in the TTN gene (TTNtv) are the most common genetic cause of dilated cardiomyopathy (DCM) but also occur as incidental findings in the general population. This study investigated factors associated with the clinical manifestation of TTNtv. Methods An international multicentre retrospective observational study was performed in families with TTNtv-related DCM. Shared frailty models were used to estimate associations of variant characteristics with lifetime risk of DCM, and logistic regression to estimate odds ratios (ORs) for individual-level clinical risk factor profiles (cardiac conditions, cardiovascular comorbidities, lifestyle) and DCM. Results A total of 3158 subjects in 1043 families with TTNtv-related DCM were studied. TTNtv-positive subjects were 21-fold more likely to develop DCM [OR, 21.21; 95% confidence interval (CI), 14.80–30.39]. Disease onset was earlier in males, but was similar for TTNtv of different types and locations. The presence of clinical risk factors was associated with earlier DCM onset (OR, 3.41; 95% CI, 2.06–5.64), with a prior history of atrial fibrillation having a two-fold increased odds of DCM (OR, 2.05; 95% CI, 1.27–3.32). The prevalence of clinical risk factors increased with age; however, the strength of the DCM association was greatest for young-onset (<30 years) disease (OR, 4.75; 95% CI, 2.35–9.60). Administration of beta-adrenergic receptor or renin-angiotensin system-blocking drugs prior to overt DCM was associated with 87% reduced odds of DCM (OR, .13; 95% CI, .08–.23). Conclusions Disease onset in TTNtv-associated familial DCM is dependent on individual patient context and is potentially modifiable by risk factor management and prophylactic therapeutic intervention.

Introduction In moderate to high-risk surgical procedures, 15–25% of patients develop a postoperative surgical site infection. Intraoperative incisional wound irrigation has the potential to reduce surgical site infections, and additional randomised controlled trials are required to provide evidence of effectiveness. Methods and analysis This protocol describes a pragmatic, adaptive, participant and adjudicator-blinded trial at 13 sites in Canada in up to 2500 participants. Participants planned for surgery with an abdominal or groin incision, who are eligible and provide verbal consent through an integrated consent model, are randomised to receive intraoperative incisional wound irrigation with povidone-iodine, saline or no irrigation. The primary outcome is surgical site infection within 30 days postoperatively. Secondary outcomes include quality of life measured 30 days postoperatively and morbidity, mortality and healthcare utilisation within 90 days postoperatively. Ethics and dissemination This trial has been approved by the research ethics board at the participating centres and stopped enrolling participants on May 23, 2025. All participants will provide verbal consent. Results will be disseminated via presentation at conferences, publication and posted on clinicaltrials.gov. Trial registration number The study is registered with http://clinicaltrial.gov ( NCT04548661 ; 14 September 2020).

Abstract Background Being able to estimate the risk of metachronous disease in a patient with colorectal cancer (CRC) could enable risk-appropriate surveillance. The aim of this study was to develop a risk-prediction model to estimate individual 10-year risk of metachronous disease following a CRC diagnosis. Methods A population-based cohort of patients with CRC was recruited soon after diagnosis between 1997 and 2012 from the United States, Canada, and Australia. Cox regression with the least absolute shrinkage and selection operator penalization was used to identify factors that predicted the risk of a new primary CRC diagnosed at least 1 year after the initial CRC diagnosis. Potential predictors included demography, anthropometry, lifestyle factors, comorbidities, personal and family cancer history, medication use, age at diagnosis, and pathological features of the first CRC. Internal validation through bootstrapping was used to evaluate the discrimination and calibration. Results We included 6085 CRC cases; 138 (2.3%) of these cases were diagnosed with metachronous disease over a median of 12 years (IQR = 5-17 years). Metachronous CRC risk was predicted by body mass index; smoking status; level of physical activity; family history of cancer and synchronous CRC; stage, grade, histological type, and DNA mismatch repair status; and age at diagnosis of the first CRC. The model was valid with a C statistic of 0.65 (95% CI = 0.63 to 0.68) and a calibration slope of 0.873 (SD = 0.087). Conclusions Metachronous CRC can be predicted with reasonable accuracy using a prediction model that consists of clinical variables collected as part of routine practice.

Purpose To develop an expert consensus statement on the diagnosis, management, and rehabilitation of medial meniscal root tears (MMRTs) using a modified Delphi technique. Methods A working group developed statements on MMRT diagnosis, nonoperative management, surgical indications, surgical management, alignment, and rehabilitation using modified Delphi techniques. Fifty‐six experts were surveyed over 3 rounds to reach consensus, with agreement measured on a 5‐point Likert scale. Statements were included, revised, or excluded on the basis of predefined thresholds (≥75% agreement, <20% disagreement). Experts suggested revisions or new statements in the first 2 rounds, and final consensus statements were included. Results All 56 experts completed 3 survey rounds. Experts agreed that root tears may occur with no known history of trauma, typically in older patients, and that it should be diagnosed with an magnetic resonance imaging. In symptomatic patients with MMRTs without advanced osteoarthritis should be repaired using an anatomic transtibial pull‐out technique (performing a pie‐crusting technique can be helpful for visualization). Nonoperative management is advised for patients with advanced osteoarthritis. High tibial osteotomy may be considered for significant varus malalignment during MMRT repair. The only statement without consensus was the management of asymptomatic MMRTs with mild medial compartment cartilage wear, indicating ongoing debate. Conclusions Overall, 98% of statements reached consensus. There is agreement that magnetic resonance imaging is the gold standard for diagnosis. Symptomatic MMRTs without advanced osteoarthritis should be repaired early using an anatomic transtibial pull‐out technique. End‐stage knee osteoarthritis warrants nonoperative management of MMRTs, and a structured postoperative protocol with limited weightbearing and range of motion is essential after repair. No agreement was reached on managing asymptomatic MMRTs in patients without significant medial compartment degeneration. Meniscal centralization sutures may help in cases of substantial extrusion, but their routine use is debated. Level of Evidence Level V, consensus of expert opinion.

Abstract Background Primary aldosteronism (PA) is a common treatable cause of hypertension. When caused by unilateral adrenal disease, it is potentially curable by adrenalectomy. However, specialized tests and other factors may delay definitive treatment. We assessed the time to adrenalectomy (TTA) for patients worldwide. Methods We conducted an international, multicentre retrospective study involving 39 centres from 15 countries to determine the total time taken from the first presentation to adrenalectomy and the intervals between each stage (screening, confirmatory, subtyping, and adrenalectomy). We included patients with PA who underwent adrenalectomy from January 1, 2018, to October 30, 2022. Post-adrenalectomy outcomes were evaluated using the Primary Aldosteronism Surgery Outcome criteria. We performed multivariable quantile and linear regression to identify characteristics associated with longer TTA. Results We included 861 patients, mean age 49.3 ± 11.1 years, and 44.5% were women. Overall median TTA was 13.5 months, IQR: 6.6-24.5. Median intervals were 0.1 months (screening), 1.0 months (confirmatory), 4.1 months (subtyping), and 4.3 months (adrenalectomy). On multivariable analysis, median TTA was increased by 5.4 months for each additional adrenal vein sampling (AVS) procedure. Other factors associated with longer TTA included adrenalectomy post-COVID-19, younger age, and additional screening tests. Compared with countries with routine AVS, those without AVS had a shorter TTA (6.1 vs 15.1 months, P &lt; .001), but greater likelihood of absent/partial biochemical success post-adrenalectomy (27.4% vs 12.4%, P &lt; .001). Conclusion Primary aldosteronism management is time-consuming worldwide, especially for subtyping tests and adrenalectomy. While omitting AVS reduces overall time, patients are less likely to achieve biochemical cure post-adrenalectomy.

Abstract Atrial fibrillation (AF) is increasingly diagnosed early, close to its first occurrence due to: (i) increased public awareness with self-screening; (ii) health care initiatives including population screening and opportunistic case finding; and (iii) increased use and surveillance of implantable cardiac devices. At its onset, AF is often low burden, and cardiovascular co-morbidities may be absent or at an early stage. Thus, the management of recent-onset AF has become an issue of growing importance. Professional guidelines have traditionally focused on anticoagulant thromboprophylaxis, generally recommending a cautious approach to rhythm control, and priority has been given to rate control to alleviate symptoms. In recent guidelines, the importance of managing lifestyle and co-morbidities has increased. The AF-SCREEN collaboration proposes that a vigorous approach to active management of recent-onset AF may be warranted. This includes addressing co-morbidities and promoting healthy lifestyles to prevent the emergence or progression of AF and associated cardiovascular disease, as well as the initiation of active rhythm control ± anticoagulation to prevent AF-related morbidity and mortality, including stroke and heart failure (HF). Intuitively, intervention early after AF onset would be beneficial since lifestyle and co-morbidity management, plus rhythm control and anticoagulation, are important contributors to improved outcomes in patients with established AF, but robust evidence is lacking for recent-onset AF. There is a delicate balance between achieving favourable outcomes such as preventing strokes, HF and AF progression vs the complications and potential adverse effects of interventions. Given the serious long-term consequences, innovative approaches are necessary to determine the value and risks of initiating active therapy very early in the course of AF. More data are needed to guide the best management of recent-onset AF, bearing AF burden in mind. Long-term studies using large national databases linked to electronic medical records and rhythm monitoring devices offer excellent opportunities. Shorter-term studies focusing on reducing AF burden to slow AF progression and studies focusing on outcomes such as HF could be used in both randomized clinical trials and observational cohort studies.