Citations

AbstractThis article aims to assist radiologists in navigating the vascular and biliary anatomy of post-transplant patients, thereby enhancing their diagnostic accuracy and determining the need for potential interventions. We have detailed established methods for anastomosis between the donor and recipient arterial, hepatic venous, portal venous, and biliary systems, while omitting surgical techniques, vascular shunting, and operative procedures, as our primary audience is radiologists. The focus of this review is on inflow and outflow of both blood and bile. Given the numerous possible anastomosis points in hepatic transplantation, familiarizing radiologists with these variations will support their efforts in identifying crucial structures in post-transplant patients.

Background Gastrointestinal cancers comprise nearly one-third of global mortality from cancer, yet the comprehensive global burden of these cancers remains uninvestigated. Objective We aimed to assess the global, regional and national burden of gastrointestinal cancers. Designs Data on oesophagus, gastric, colorectal, liver, pancreas and biliary tract cancers were extracted from the Global Burden of Disease 2021 database. Age-standardised incidence rate (ASIR) and age-standardised death rate (ASDR) were calculated by sex, region and Sociodemographic Index (SDI). Results In 2021, there were 5.26 million incidences and 3.70 million deaths from gastrointestinal cancer. The greatest burden is from colorectal, followed by gastric, oesophageal, pancreatic, liver and biliary tract cancer. We noted geographical and socioeconomic differences in ASIR and ASDR across all types of cancers. From 2000 to 2021, ASIR increased for colorectal cancer (annual percent change (APC): 0.10%, 95% CI 0.05% to 0.14%), pancreatic cancer (APC: 0.27%, 95% CI 0.14% to 0.41%), and liver cancer from metabolic dysfunction-associated steatotic liver disease (APC: 0.62%, 95% CI 0.58% to 0.67%) and alcohol-related liver disease (APC: 0.26%, 95% CI 0.22% to 0.30%). ASDR increased for pancreatic cancer (APC: 0.18%, 95% CI 0.02% to 0.34%). Higher SDI countries had higher incidence rates for most types of gastrointestinal cancer. Conclusions Although the ASIR of oesophageal, gastric and biliary tract cancer has decreased, the ASIR still increased in colorectal, pancreatic and liver cancer from steatotic liver disease. Public policies are important for controlling gastrointestinal cancers—most importantly, reducing alcohol consumption, hepatitis B immunisation and tackling the burden of metabolic diseases.

AbstractThe Clinical and Laboratory Standards Institute (CLSI) H62—Validation of Assays Performed by Flow Cytometry guideline, released in 2021, provides recommendations for platform workflow and quality system essentials, instrument setup and standardization, assay development and optimization and fit‐for‐purpose analytical method validation. In addition, CLSI H62 includes some recommendations for the validation strategies after a validated flow cytometric method has been modified. This manuscript builds on those recommendations and discusses the impact of different types of assay modifications on assay performance. Recommendations regarding which validation parameters to evaluate depending on the type of modification are provided. The impact of assay modification on the assay's intended use is discussed. When recommending minor deviations from the CLSI H62 process for a laboratory‐initiated assay revision (e.g., specimen numbers for sensitivity, specificity, or precision studies), a rationale based on expert opinion is provided with the understanding that not every laboratory, assay type, and circumstance can be comprehensively addressed in this paper. These recommendations are meant as a practical recommendation and are not intended to be restrictive, prescriptive, or understood as necessarily sufficient to meet every specific requirement from regulatory bodies (e.g., FDA or New York State Department of Health).

Background Piecemeal endoscopic mucosal resection (EMR) is an acceptable technique for T1a esophageal adenocarcinoma, but en bloc R0 excision is advocated for T1b disease as it may offer a potential cure and mitigate recurrence. Thus, distinguishing between T1a and T1b disease is imperative under current treatment paradigms. We investigated whether expert Barrett’s endoscopists could make this distinction based on optical evaluation. Methods Endoscopic images of histologically confirmed high grade dysplasia (HGD), T1a, and T1b disease (20 sets for each) were compiled from consecutive patients at a single institution. Each set contained four images including an overview, a close-up in high definition white light, a near-focus magnification image, and a narrow-band image. Experts predicted the histology for each set. Results 19 experts from 8 countries (Australia, USA, Italy, Netherlands, Germany, Canada, Belgium, and Portugal) participated. The majority had been practicing for > 20 years, with a median (interquartile range) annual case volume of 50 (18–75) for Barrett’s EMR and 25 (10–45) for Barrett’s endoscopic submucosal dissection. Esophageal adenocarcinoma (T1a/b) could be distinguished from HGD with a pooled sensitivity of 89.1 % (95 %CI 84.7–93.4). T1b adenocarcinoma could be predicted with a pooled sensitivity of 43.8 % (95 %CI 29.9–57.7). Fleiss’ kappa was 0.421 (95 %CI 0.399–0.442; P < 0.001), indicating fair-to-moderate agreement. Conclusions Expert Barrett’s endoscopists could reliably differentiate T1a/T1b esophageal adenocarcinoma from HGD. Despite fair-to-moderate agreement for T staging, T1b disease could not be reliably distinguished from T1a disease. This may impact clinical decision making and selection of endoscopic techniques.

The incidence of early-onset colorectal cancer (EO-CRC) in individuals under 50 years old is rapidly increasing in the United States. This study aims to evaluate EO-CRC incidence rates using data from the Global Burden of Disease Study (GBD) 2021, providing insights into trends from 1990 to 2021. We employed an age–period–cohort (APC) model analysis to estimate the effects of age, time period, and birth cohort on EO-CRC incidence. Our findings indicate that the number of EO-CRC cases rose from 6256 (95% UI: 6059–6456) in 1990 to 9311 (95% UI: 8859–9744) in 2021, a 49% increase from 1990 to 2021. The age-standardized incidence rate per 100,000 population increased by 34% during this period. The net drift in females (0.22%, 95% CI: 0.20–0.24) was slightly higher than in males (0.21%, 95% CI: 0.19–0.23) (p = 0.45). The APC analysis revealed that being over 25 years old, the period from 2005–2021, and being born after 1983 negatively impacted EO-CRC incidence rates, with a sharp rise after 2000 and a reduction among females from 2017 to 2021. Our study highlights the need for targeted prevention strategies and further research to understand these trends.

Background: While bariatric surgery may reduce obesity-associated inflammation, alterations in gut microbiome and nutrition could impact inflammatory bowel disease (IBD) risk. This study aimed to investigate the association between bariatric surgery and new onset IBD. Methods: A systematic review and meta-analysis of observational studies was conducted from inception to 31 January 2024. Risk estimates were pooled using a DerSimonian and Laird random-effects model, and adjusted hazards ratios (HRs) with corresponding 95% confidence interval (CI) were reported. The modified Newcastle-Ottawa Quality Assessment Scale (NOS) was used to examine the risk of bias. Results: Of 98 articles screened, four studies comprising 4,727,600 participants were included in the systematic review and two studies in the meta-analysis. Included studies had high quality and low risk of bias according to NOS. The pooled analysis revealed a significant risk of new onset IBD (HR: 1.28, 95% CI: 1.04–1.53, I2 = 74.9%), particularly Crohn’s disease (HR: 1.75, 1.59–1.92, I2 = 0), following bariatric surgery, but no significant risk of ulcerative colitis (HR: 0.93, 0.75–1.11, I2 = 11.5%). Conclusions: This meta-analysis found that bariatric surgery was associated with a higher risk of developing Crohn’s disease. Patients should be counseled on IBD risk pre-surgery, and symptomatic patients should be evaluated post-surgery to enable early diagnosis and management.

AbstractPrior studies have suggested that immune thrombotic thrombocytopenic purpura (iTTP) may display seasonal variation; however, methodologic limitations and sample sizes have diminished the ability to perform a rigorous assessment. This 5‐year retrospective study assessed the epidemiology of iTTP and determined whether it displays a seasonal pattern. Patients with both initial and relapsed iTTP (defined as a disintegrin and metalloprotease with thrombospondin type motifs 13 activity <10%) from 24 tertiary centers in Australia, Canada, France, Greece, Italy, Spain, and the US were included. Seasons were defined as: Northern Hemisphere—winter (December–February); spring (March–May); summer (June–August); autumn (September–November) and Southern Hemisphere—winter (June–August); spring (September–November); summer (December–February); autumn (March–May). Additional outcomes included the mean temperature in months with and without an iTTP episode at each site. A total of 583 patients experienced 719 iTTP episodes. The observed proportion of iTTP episodes during the winter was significantly greater than expected if equally distributed across seasons (28.5%, 205/719, 25.3%–31.9%; p = .03). Distance from the equator and mean temperature deviation both positively correlated with the proportion of iTTP episodes during winter. Acute iTTP episodes were associated with the winter season and colder temperatures, with a second peak during summer. Occurrence during winter was most pronounced at sites further from the equator and/or with greater annual temperature deviations. Understanding the etiologies underlying seasonal patterns of disease may assist in discovery and development of future preventative therapies and inform models for resource utilization.

ABSTRACT Taniborbactam, a bicyclic boronate β-lactamase inhibitor with activity against Klebsiella pneumoniae carbapenemase (KPC), Verona integron–encoded metallo-β-lactamase (VIM), New Delhi metallo-β-lactamase (NDM), extended-spectrum beta-lactamases (ESBLs), OXA-48, and AmpC β-lactamases, is under clinical development in combination with cefepime. Susceptibility of 200 previously characterized carbapenem-resistant K. pneumoniae and 197 multidrug-resistant (MDR) Pseudomonas aeruginosa to cefepime-taniborbactam and comparators was determined by broth microdilution. For K. pneumoniae (192 KPC; 7 OXA-48-related), MIC 90 values of β-lactam components for cefepime-taniborbactam, ceftazidime-avibactam, and meropenem-vaborbactam were 2, 2, and 1 mg/L, respectively. For cefepime-taniborbactam, 100% and 99.5% of isolates of K. pneumoniae were inhibited at ≤16 mg/L and ≤8 mg/L, respectively, while 98.0% and 95.5% of isolates were susceptible to ceftazidime-avibactam and meropenem-vaborbactam, respectively. For P. aeruginosa , MIC 90 values of β-lactam components of cefepime-taniborbactam, ceftazidime-avibactam, ceftolozane-tazobactam, and meropenem-vaborbactam were 16, >8, >8, and >4 mg/L, respectively. Of 89 carbapenem-susceptible isolates, 100% were susceptible to ceftolozane-tazobactam, ceftazidime-avibactam, and cefepime-taniborbactam at ≤8 mg/L. Of 73 carbapenem-intermediate/resistant P. aeruginosa isolates without carbapenemases, 87.7% were susceptible to ceftolozane-tazobactam, 79.5% to ceftazidime-avibactam, and 95.9% and 83.6% to cefepime-taniborbactam at ≤16 mg/L and ≤8 mg/L, respectively. Cefepime-taniborbactam at ≤16 mg/L and ≤8 mg/L, respectively, was active against 73.3% and 46.7% of 15 VIM- and 60.0% and 35.0% of 20 KPC-producing P. aeruginosa isolates. Of all 108 carbapenem-intermediate/resistant P. aeruginosa isolates, cefepime-taniborbactam was active against 86.1% and 69.4% at ≤16 mg/L and ≤8 mg/L, respectively, compared to 59.3% for ceftolozane-tazobactam and 63.0% for ceftazidime-avibactam. Cefepime-taniborbactam had in vitro activity comparable to ceftazidime-avibactam and greater than meropenem-vaborbactam against carbapenem-resistant K. pneumoniae and carbapenem-intermediate/resistant MDR P. aeruginosa .

To identify medical phrases utilized by the critical care team that may have an unintended impact on the critically ill patient, we administered an anonymous survey to multi-professional critical care team members. We elicited examples of imprecise language that may have a negative emotional impact on the critically ill. Of the 1600 providers surveyed, 265 offered 1379 examples (912 unique) which were clustered into 5 categories. Medical jargon (eg, “riding the vent”) was most prevalent (n = 549). There were 217 negative suggestions (eg, “you will feel a stick and a burn”). Hyperboles (eg, “black cloud”) were common (n = 198) while homonyms (ie “he fibbed”) accounted for 150 examples. Phrases such as “code brown in there” were categorized as metonyms (n = 144). 121 metaphors/similes (eg, “rearranging deck chairs on the Titanic”) were provided. Phrases that have the potential to negatively impact critically ill patient perceptions are commonplace in critical care practice. Whether these everyday communication habits lead to an unintended nocebo effect on mental health outcomes of the critically ill deserves further study.

Importance The clinical effects of risankizumab (a monoclonal antibody that selectively targets the p19 subunit of IL-23) for the treatment of ulcerative colitis are unknown. Objective To evaluate the efficacy and safety of risankizumab when administered as an induction and a maintenance therapy for patients with ulcerative colitis. Design, Setting, and Participants Two phase 3 randomized clinical trials were conducted. The induction trial was conducted at 261 clinical centers (in 41 countries) and enrolled 977 patients from November 5, 2020, to August 4, 2022 (final follow-up on May 16, 2023). The maintenance trial was conducted at 238 clinical centers (in 37 countries) and enrolled 754 patients from August 28, 2018, to March 30, 2022 (final follow-up on April 11, 2023). Eligible patients had moderately to severely active ulcerative colitis; a history of intolerance or inadequate response to 1 or more conventional therapies, advanced therapies, or both types of therapies; and no prior exposure to risankizumab. Interventions For the induction trial, patients were randomized 2:1 to receive 1200 mg of risankizumab or placebo administered intravenously at weeks 0, 4, and 8. For the maintenance trial, patients with a clinical response (determined using the adapted Mayo score) after intravenous treatment with risankizumab were randomized 1:1:1 to receive subcutaneous treatment with 180 mg or 360 mg of risankizumab or placebo (no longer receiving risankizumab) every 8 weeks for 52 weeks. Main Outcomes and Measures The primary outcome was clinical remission (stool frequency score ≤1 and not greater than baseline, rectal bleeding score of 0, and endoscopic subscore ≤1 without friability) at week 12 for the induction trial and at week 52 for the maintenance trial. Results Among the 975 patients analyzed in the induction trial (aged 42.1 [SD, 13.8] years; 586/973 [60.1%] were male; and 677 [69.6%] were White), the clinical remission rates at week 12 were 132/650 (20.3%) for 1200 mg of risankizumab and 20/325 (6.2%) for placebo (adjusted between-group difference, 14.0% [95% CI, 10.0%-18.0%], P &amp;lt; .001). Among the 548 patients analyzed in the maintenance trial (aged 40.9 [SD, 14.0] years; 313 [57.1%] were male; and 407 [74.3%] were White), the clinical remission rates at week 52 were 72/179 (40.2%) for 180 mg of risankizumab, 70/186 (37.6%) for 360 mg of risankizumab, and 46/183 (25.1%) for placebo (adjusted between-group difference for 180 mg of risankizumab vs placebo, 16.3% [97.5% CI, 6.1%-26.6%], P &amp;lt; .001; adjusted between-group difference for 360 mg of risankizumab vs placebo, 14.2% [97.5% CI, 4.0%-24.5%], P = .002). No new safety risks were detected in the treatment groups. Conclusion and Relevance Compared with placebo, risankizumab improved clinical remission rates in an induction trial and in a maintenance trial for patients with moderately to severely active ulcerative colitis. Further study is needed to identify benefits beyond the 52-week follow-up. Trial Registration ClinicalTrials.gov Identifiers: NCT03398148 and NCT03398135