Citations

Objectives: Participant retention is essential in prospective studies to minimize bias and maintain validity. This study aimed to estimate retention rates and identify factors influencing attrition in a multicenter cohort (PROCEED) of US adults with acute/recurrent acute pancreatitis (AP/RAP) and chronic pancreatitis (CP). Methods: Participants from the PROCEED study with AP/RAP or CP eligible for follow-up within the designated visit window were included. Retention was defined as completing at least one follow-up visit during the observation period. Retention was analyzed by follow-up mode (in-person and/or medical record review) and disease type (AP/RAP and CP). Retention factors were assessed using univariate analyses (Wilcoxon rank-sum for continuous variables, χ 2 /Fisher's exact for categorical) and multivariable logistic regression. Missing data were adjusted using multiple imputations in statistical modeling. Results: Among 1279 participants (AP/RAP: n=632, median age 47, 48.9% female; CP: n=647, median age 54, 46.5% female), we observed high cumulative and annualized retention rates, with improved retention when incorporating medical record reviews. In multivariable regression analyses, older age was statistically significantly associated with in-person retention in the AP/RAP group ( P =0.0001), while a higher self-reported physical health (assessed with PROMIS Global Health Physical Health T-score) was a key predictor of retention in CP ( P =0.034). Conclusions: Integrating medical records review substantially enhanced retention rates, enabling robust analyses of pancreatitis outcomes and disease progression. Older age and better self-reported physical health were key predictors of retention, highlighting the need for targeted strategies to enhance engagement among younger participants and those with poorer health in long-term studies.

Objective To investigate the diagnostic performance of perilesional biopsies (PLBx) compared to other biopsy strategies, assessing the impact of the Prostate Imaging‐Reporting and Data System (PI‐RADS) score and biopsy history in patients with a visible lesion at multiparametric magnetic resonance imaging of the prostate (mpMRI), as the European Association of Urology guidelines recommend combining MRI‐targeted biopsies (TBx) with PLBx as an alternative to systematic biopsies (SBx) even though evidence is limited. Patients and Methods We relied on a cohort of 2852 patients with PI‐RADS ≥3 lesions undergoing TBx + SBx at three tertiary referral centres. The primary outcome was detection of clinically significant PCa (csPCa) (International Society of Urological Pathology Grade Group [ISUP GG] ≥2) of TBx + PLBx vs TBx + SBx. Results were stratified by PI‐RADS score and biopsy history. The PLBx cores were defined as samples taken from prostate sectors adjacent to the mpMRI lesion. We finally assessed insignificant PCa (insPCa, i.e., ISUP GG 1) detection across biopsy strategies. Differences were assessed using the chi‐square test. Results Detection of csPCa was 48%. Overall, TBx + SBx had a higher csPCa detection rate than TBx + PLBx (50% vs 45%, P = 0.03), particularly in PI‐RADS 3 lesions (26% vs 21%, P = 0.02) and active surveillance (AS) patients (46% vs 40%, P = 0.04). No significant differences were found in PI‐RADS 4 (53% vs 50%, P > 0.1) or PI‐RADS 5 (76% vs 75%, P > 0.1). In the biopsy naïve and previous negative biopsy groups, csPCa detection was similar between strategies ( P > 0.1). Conclusions Overall, TBx + SBx offers the highest detection of csPCa. Even though TBx + PLBx may be considered in PI‐RADS 4–5 lesions to reduce insPCa detection, TBx + SBx remains the preferred strategy for PI‐RADS 3 and AS patients.

Importance Inherited pathogenic variants (PVs) in known predisposition genes can greatly increase breast cancer risk, but the combined impact of PV status, family history, and other factors on breast cancer risk in the general US population has not been well described. Objective To evaluate population-based breast cancer risk estimates for those with established PVs overall and stratified by first-degree family history of breast cancer and other factors. Design, Setting, and Participants This study used pooled data from 13 US-based breast cancer case-control studies participating in the Cancer Risk Estimates Related to Susceptibility (CARRIERS) consortium. Enrollment for individual studies occurred between 1976 and 2013, and results are based on data released March 2023, with analyses conducted from June 2022 to July 2025. Exposures PVs, breast cancer family history, self-reported race and ethnicity, and established risk factors. Main Outcomes and Measures Breast cancer rate ratios for PVs in 7 genes were estimated from the CARRIERS consortium. PV status and incidence and mortality statistics were combined using the Individualized Coherent Absolute Risk Estimation (iCARE) model to estimate conditional cumulative breast cancer risks and 95% CIs, stratified by family history and standardized to the US population. Models that incorporated population-based data and published estimates for established epidemiologic risk factors were also evaluated. Results A total of 67 692 women were studied, including 33 841 who were diagnosed with breast cancer. PVs in ATM , BRCA1 , BRCA2 , CHEK2 , and PALB2 were strongly associated with breast cancer risk, with BRCA1 and PALB2 PVs showing evidence of heterogeneity by family history. In models considering PVs, family history, and established risk factors, the estimated cumulative risks of breast cancer by age 50 years ranged from 2.4% (95% CI, 2.4-2.4) in women with no PVs and no family history to 35.5% (95% CI, 21.6-55.1) in PALB2 PV carriers with a family history. Among women who have not been diagnosed with breast cancer by age 50 years, the cumulative risk of breast cancer by age 80 years ranged from 11.1% (95% CI, 11.0-11.2) in noncarriers with no family history to 70.5% (95% CI, 52.8-83.5) for PALB2 carriers with a family history. PV-specific cumulative risk estimates varied across subgroups defined by race and ethnicity and potentially modifiable epidemiologic risk factors. Conclusions and Relevance In this study, population-based estimates of cumulative breast cancer risk for established PVs, as informed by the CARRIERS case-control sample, varied by family history and potentially modifiable risk factors. These estimates provide guidance for identifying individuals who will most benefit from enhanced screening and prevention strategies.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Hematopoietic Cell Transplantation (HCT) provide expert, multidisciplinary recommendations for autologous and allogeneic HCT based on current evidence. The NCCN Guidelines focus on pretransplant recipient evaluation, hematopoietic cell mobilization, conditioning, and the diagnosis and management of graft-versus-host disease (GVHD), a common complication of allogeneic HCT that is associated with significant morbidity. This selection from the NCCN Guidelines for HCT focuses on the diagnosis, workup, and management of acute and chronic GVHD, as well as important supportive care considerations.

Background Sinonasal pathology, such as chronic inflammatory disease or neoplasm, can cause secondary nasolacrimal duct obstruction (sNLDO). There is a paucity of data on dacryocystorhinostomy (DCR) techniques and outcomes for NLDO secondary to known sinonasal pathologies. Objective To describe case characteristics, management, and surgical outcomes of sNLDO at a tertiary academic center. Methods Charts of DCR cases with at least 3 months follow-up done at a single institution over a 5-year period (2018-2022) were reviewed. Patient and surgical characteristics were recorded and compared between secondary and primary NLDO groups. The primary outcome was early functional success of DCR, assessed by improvement or resolution of epiphora at 3 months. Results A total of 236 cases were included. Of those, 79 (33.5%) were classified as secondary NLDO associated with sinonasal pathology. Reasons for sNLDO were sinonasal cancer (46.8%), chronic inflammatory disease (24.1%), trauma (16.5%), or prior head and neck radiation (31.6%). When comparing primary acquired NLDO to sNLDO cases, DCR for sNLDO was more likely to be performed endoscopically (68.4% vs 31.8%, P < .01), by a multidisciplinary team of rhinologist and oculoplastic surgeon (70.9% vs 8.3%, P < .01), and required bilateral surgery (36.7% vs 5.7%, P < .01). The overall functional success rate was 79.7% for sNLDO compared to 87.9% for primary acquired NLDO ( P < .01). Revision surgery for sNLDO, history of sinonasal malignancy, and radiation were associated with lower functional success rates (66.7%, 70.3%, and 68.0%, respectively). Canalicular pathology was more common in sNLDO cases (29.0% vs 8.3%, P < .01). Conclusions Secondary NLDO was more commonly managed with an endoscopic approach by a multidisciplinary team. Revisions for sNLDO, as well as cases with a history of sinonasal malignancy and radiation, had a markedly lower success rate, and sNLDO was frequently associated with canalicular obstruction. These findings may facilitate surgical planning and patient counseling.

Abstract Background Photon counting detector CT (PCD‐CT) has the potential to sort detected x‐ray photons into more than two energy bins to perform multi‐material decomposition using K‐edge materials without additional mathematical constraints/assumptions. The availability of multiple energy thresholds in PCD‐CT opens the possibility for unique clinical applications such as simultaneous multi‐contrast‐agent imaging. Purpose To evaluate the technical performance of a PCD‐CT system with four energy thresholds for conducting multi‐material decomposition of iodine, gadolinium, and water after a comprehensive system calibration procedure. Methods Experiments were performed on a commercial PCD‐CT scanner (NAEOTOM Alpha, Siemens Healthineers) using a research mode with four energy thresholds. Material calibration was performed by scanning contrast materials with known concentration placed in various sizes of cylindrical water‐equivalent phantoms at various tube currents and positions. From these data, per‐voxel contrast models were derived for each material by multiple linear regressions up to second order, where the predictor variables were combinations of tube current, phantom diameter, and distance to isocenter. After calibration, small (20 cm diameter) and large (30 cm × 40 cm) uniform multi‐energy CT phantoms and an anthropomorphic thorax phantom (31 cm × 39 cm), each containing bone, soft tissue, and several quantitative inserts of iodine (0.2–5.0 mg/ml), gadolinium (0.3–5.0 mg/ml), and a mixture of both (5.0 mg/ml each) were scanned using the four‐energy threshold mode at 140 kV with energy thresholds set at 20, 52, 75, and 82 keV. Images for each energy threshold were reconstructed with a filtered back‐projection algorithm and a quantitative kernel (Qr44). Subsequent image‐based material decomposition was performed on individual voxels of the energy threshold images using the models derived from the calibration process to generate water, iodine, and gadolinium basis images. Quantitative material concentrations and image noise magnitudes, and noise power spectra (NPS) were measured. Results Iodine and gadolinium concentrations above 1.25 mg/ml were visible in the material basis images in all phantoms. Averaged quantitative accuracy for iodine and gadolinium in the small, large, and thorax phantoms were 0.39 ± 0.30 mg/ml, 0.96 ± 0.53 mg/ml, and 0.53 ± 0.35 mg/ml, respectively. In the water basis images, accuracy was within 24 HU in all phantoms. Noise magnitudes in iodine and gadolinium basis images were 2.91 and 3.52 times that of the lowest energy threshold image for the small phantom, and were 6.92 and 7.17 times that of the lowest threshold image for the large phantom. Noise texture did not change between the energy threshold and material basis images for either size phantom as measured by the NPS. Conclusions After a comprehensive system calibration, a commercial PCD‐CT with four energy thresholds performed multiple material decomposition of iodine, gadolinium, and water for concentrations above 1.25 mg/ml in human‐sized phantoms. Noise amplification and quantitative accuracy from the decomposition greatly depended on object size.

Background: Venous malformations can cause substantial morbidity and long-term complications. There are no Food and Drug Administration (FDA)-approved therapies for the treatment of venous malformations. However, off-label use of sirolimus has demonstrated clinical benefit in these patients. This systematic review evaluates the efficacy and safety of sirolimus in the management of venous malformations. Methods and Results: A systematic literature search identified 26 studies comprising 98 patients treated with sirolimus for venous malformations. Most studies were case reports or case series (77%), with 15% prospective trials and 8% retrospective analyses. Sirolimus, primarily administered orally, yielded some level of clinical improvement in 72% of reported patients, with consistent symptomatic relief observed in coagulopathy, bleeding, anemia, pain, and improved function. However, reduction in the size of the malformation varied and treatment-limiting side effects were observed. Conclusions: Oral sirolimus is a promising treatment option for venous malformations, especially for those with deep venous malformations. A direct, targeted topical treatment could provide clinical benefit for the cutaneous manifestation without the risk of off-target effects as occur with oral sirolimus. Further prospective, controlled studies are warranted to elucidate sirolimus’s role in managing venous malformations.

Importance Annual rates of first intracranial hemorrhage (ICH) from unruptured brain arteriovenous malformations (AVMs) are often quoted as 2% to 4% in clinical practice. Precise estimates and risk factors are unavailable to inform treatment decisions. Objective To provide estimates of rates and risk factors for first ICH in a large cohort study of unruptured brain AVMs. Design, Setting, and Participants The Multicenter Arteriovenous Malformation Research Study (MARS) included data from 9 cohorts, each contributing 100 or more unruptured brain AVMs. The study was conducted from 2017 to 2023 with retrospective and prospective data collection for existing cohorts and/or new recruitment. This was an international study (2 population-based and 7 referral-based cohorts) that included participants diagnosed with an unruptured brain AVM. Exposures Demographic, clinical, and angiographic characteristics. Main Outcome and Measure The primary outcome was time to first ICH after diagnosis of unruptured brain AVM. Data were collected using standardized definitions; missing data were imputed. Cox regression analysis was performed, censoring at first brain AVM treatment, death, or last visit, and allowing baseline hazards to vary by cohort. Results A total of 3225 individuals were eligible for participation in this study. After 195 exclusions, 3030 participants (median [IQR] age, 38 [25-50] years; 1524 female [50.3%]) were included. Among 2989 participants with unruptured brain AVMs, 1333 (45%) presented with seizure. The median (IQR) maximal brain AVM diameter was 3.1 (2.2-4.4) cm, 248 of 2466 AVMs (10%) had exclusively deep venous drainage, 297 of 2690 (11%) were in supratentorial deep or cerebellar locations, and 457 of 2440 (19%) had associated arterial aneurysms. First ICH occurred in 159 participants over 11 339 person-years of follow-up for an ICH rate of 1.40 (95% CI, 1.20-1.64) per 100 person-years. Significant independent risk factors included (1) increasing age category at diagnosis (hazard ratio [HR], 0.87; 95% CI, 0.53-1.41 for those aged 20 to 39 years; HR, 1.23; 95% CI, 0.74-2.04 for those aged 40 to 59 years; and HR, 2.01; 95% CI, 1.14-3.57 for those aged 60 years vs younger than 20 years; P = .008), (2) presence of associated aneurysms (HR, 1.66; 95% CI, 1.06-2.59; P = .03), and (3) cerebellar or supratentorial deep location (HR, 1.87; 95% CI, 1.16-3.00; P = .01). Conclusions and Relevance The annual ICH rate from unruptured brain AVM was lower than that commonly cited in clinical practice. Increasing age, associated arterial aneurysms, and cerebellar or supratentorial deep brain AVM location were associated with risk of first ICH. These results may be used to counsel patients about the natural history of unruptured brain AVMs.