Citations

This selection from the NCCN Guidelines for Adolescent and Young Adult (AYA) Oncology focuses on considerations for the comprehensive care of AYA patients with cancer. Compared with older adults with cancer, AYA patients have unique needs regarding treatment, fertility counseling, psychosocial and behavioral issues, and supportive care services. The complete version of the NCCN Guidelines for Adolescent and Young Adult (AYA) Oncology addresses additional aspects of caring for AYA patients, including risk factors, screening, diagnosis, and survivorship.

Introduction: There is an increasing interest in cold snare endoscopic mucosal resection (CS-EMR), and studies have shown its safety and efficacy for colonic polyps. This meta-analysis aims to assess the safety and efficacy of CS-EMR for the removal of duodenal adenomas. Methods: We conducted a comprehensive literature search of several databases, from inception through February 2023, for studies that addressed outcomes of CS-EMR for nonampullary duodenal adenomas. We used the random-effects model for the statistical analysis. The weighted pooled rates were used to summarize the technical success, polyp recurrence, bleeding, and perforation events. Cochran Q test and I 2 statistics adjudicated heterogeneity. Results: Six studies were included in the analysis. In all, 178 duodenal polyps were resected using CS-EMR. The pooled rates were 95.8% (95% CI 89.1–98.5%, I 2=21.5%) for technical success and 21.2% (95% CI 8.5–43.6%, I 2=78%) for polyp recurrence. With regards to CS-EMR safety, the pooled rates were 4.2% (95% CI 1.6–10.5%, I 2=12%) for immediate bleeding, 3.4% (95% CI 1.5–7.6%, I 2=0%) for delayed bleeding, 2.8% (95% CI 1.1–6.7%, I 2=0%) for perforation, and 2% (95% CL 0.5–7.5%, I 2=0%) for post-polypectomy syndrome. Rates were not significantly different for large adenomas. Three studies reported data on CS-EMR and conventional EMR. Compared with conventional EMR, CS-EMR had lower odds of delayed bleeding, OR 0.11 (CI 0.02–0.62, P value 0.012, I 2=0%). Conclusion: Our findings suggest that CS-EMR is a safe and effective strategy for the resection of nonampullary duodenal adenomas, with an acceptable recurrence rate. Data from larger randomized controlled studies are needed to validate our findings.

Abstract Motivation Analyzing the overlap between two sets of genomic intervals is a frequent task in the field of bioinformatics. Typically, this is accomplished by counting the number (or proportion) of overlapped regions, which applies an arbitrary threshold to determine if two genomic intervals are overlapped. By making binary calls but disregarding the magnitude of the overlap, such an approach often leads to biased, non-reproducible, and incomparable results. Results We developed the cobind package, which incorporates six statistical measures: the Jaccard coefficient, Sørensen–Dice coefficient, Szymkiewicz–Simpson coefficient, collocation coefficient, pointwise mutual information (PMI), and normalized PMI. These measures allow for a quantitative assessment of the collocation strength between two sets of genomic intervals. To demonstrate the effectiveness of these methods, we applied them to analyze CTCF’s binding sites identified from ChIP-seq, cancer-specific open-chromatin regions (OCRs) identified from ATAC-seq of 17 cancer types, and oligodendrocytes-specific OCRs identified from scATAC-seq. Our results indicated that these new approaches effectively re-discover CTCF’s cofactors, as well as cancer-specific and oligodendrocytes-specific master regulators implicated in disease and cell type development. Availability and implementation The cobind package is implemented in Python and freely available at https://cobind.readthedocs.io/en/latest/.

AbstractIntroductionMinimum clinically important differences (MCIDs) are critical to understanding changes in patient-reported outcome measure (PROM) scores after total joint arthroplasty (TJA). The usage and adoption of MCIDs not been well-studied. This study was performed to IDENTIFY trends in PROM and MCID use after TJA over the past decade.MethodsAll articles published in the calendar years of 2010 and 2020 in CORR, JBJS, and the Journal of Arthroplasty were reviewed. Articles relating to clinical outcomes in primary total hip arthroplasty (THA) or total knee arthroplasty (TKA) were included. For each article, all reported PROMs and (if present) accompanying MCIDs were recorded. The use of PROMs and MCIDs were compared between articles published in 2010 and 2020.ResultsOverall, 263 articles from 2010 and 546 articles from 2020 were included. The total number of articles reporting any PROM after THA and TKA increased from 131 in 2010 to 194 in 2020, but the proportion of articles reporting PROMs decreased from 49.8% (131/263) to 35.5% (194/546). Both the total number and proportion of articles reporting MCIDs increased from 2.3% (3/131) in 2010 to 16.5% (32/194) in 2020. These trends persisted when analyzing THA and TKA articles individually.ConclusionsBoth the absolute number and proportion of articles reporting MCIDs in conjunction with PROMs after TJA has increased in the past decade but remains low. We recommend that journal editors and meeting organizers encourage the inclusion of MCID information in all reports on clinical outcomes after joint replacement.

AbstractIntroductionAdverse reactions to pain medication and pain can delay discharge after outpatient knee arthroplasty (TKA). Pharmacogenomics is an emerging tool that might help reduce adverse events by tailoring medication use based on known genetic variations in the CYP genes determining drug metabolism. This study was undertaken to evaluate whether pre-operative pharmacogenomic testing could optimize peri-operative pain management in patients undergoing total knee arthroplasty (TKA).MethodsThis prospective, randomized study was performed in adults undergoing primary TKA. Patients in the experimental group underwent pre-operative pharmacogenomic evaluation and medication adjustments. Medications were not optimized for control patients. The Overall Benefit of Analgesic Score (OBAS) at 24 hours post-op was the primary outcome. Postoperative pain scores (VAS scale), total opioid use, time in recovery, and time to discharge were also compared.Results76 patients enrolled. 93% of patients had a poor-intermediate phenotype for at least one of four CYP genes. OBAS did not differ significantly between the two groups (4.2 control vs. 4.7 experimental; 95% CI −1.1 to 2.1) and was below the minimum clinically important difference of 2.0 points. Furthermore, there were no differences in any OBAS subscale including pain, satisfaction, or nausea. There were no differences in time in the recovery area or to discharge from hospital, or narcotic use.ConclusionsDespite many patients having a poor-intermediate phenotype for a CYP gene, pharmacogenomic testing prior to TKA and medication adjustment did not improve anesthesia or pain management outcomes, time to discharge or mean total opioid use after surgery.

AbstractIntroductionThe optimal alignment technique for total knee replacement (TKR) remains controversial. We previously reported six-month and two-year results of a randomized controlled trial comparing kinematically (KA) versus mechanically (MA) aligned TKR. In the present study, we report 12-year results from this trial.MethodsThe original cohort included 88 TKRs (44 KA using Shape Match patient-specific guides and 44 MA using conventional instrumentation), performed from 2008 to 2009. After IRB approval, the health record of the original 88 patients were queried. Revisions, re-operations, and complications were recorded. The non-deceased patients were contacted via phone. Reoperation and complications were documented via the patient's history. Further, a battery of patient-reported outcome measures (including patient satisfaction, WOMAC, Oxford, KOOS Jr, Forgotten Joint Score, and M-SANE) were obtained.ResultsOf the original 88 patients in the study, 15 patients had a least one reoperation (17%). Patella problems were the most common cause of reoperation accounting for 5/8 reoperations in the KA group versus 3/7 in the MA group. There was no statistically significant difference between the two alignment methods in terms of major and minor complications or reoperations. At the 12-year follow-up, 26 patients died leaving 62 patients for follow-up. Of these, 48 patients (77%) were successfully contacted. The kinematically aligned total knees self-reported better satisfaction (96% versus 82%), but no difference in other patient-reported outcome measures compared to mechanically aligned TKRs.ConclusionKA TKR demonstrates excellent mid to long-term results compared to MA TKR with similar reoperations, complications, and patient-reported outcome measures.

AbstractIntroductionLeft bundle branch area pacing (LBBP) is a novel conduction system pacing method to achieve effective physiological pacing and an alternative to cardiac resynchronization therapy (CRT) with biventricular pacing (BVP) for patients with heart failure with reduced ejection fraction (HFrEF). We conduted this meta‐analysis and systemic review to review current data comparing BVP and LBBP in patients with HFrEF and indications for CRT.MethodsWe searched PubMed/Medline, Web of Science, and Cochrane Library from the inception of the database to November 2022. All studies that compared LBBP with BVP in patients with HFrEF and indications for CRT were included. Two reviewers performed study selection, data abstraction, and risk of bias assessment. We calculated risk ratios (RRs) with the Mantel–Haenszel method and mean difference (MD) with inverse variance using random effect models. We assessed heterogeneity using the I2 index, with I2 > 50% indicating significant heterogeneity.ResultsTen studies (9 observational studies and 1 randomized controlled trial; 616 patients; 15 centers) published between 2020 and 2022 were included. We observed a shorter fluoroscopy time (MD: 9.68, 95% confidence interval [CI]: 4.49–14.87, I2 = 95%, p < .01, minutes) as well as a shorter procedural time (MD 33.68, 95% CI: 17.80–49.55, I2 = 73%, p < .01, minutes) during the implantation of LBBP CRT compared to conventional BVP CRT. LBBP was shown to have a greater reduction in QRS duration (MD 25.13, 95% CI: 20.06–30.20, I2 = 51%, p < .01, milliseconds), a greater left ventricular ejection fraction improvement (MD: 5.80, 95% CI: 4.81–6.78, I2 = 0%, p < .01, percentage), and a greater left ventricular end‐diastolic diameter reduction (MD: 2.11, 95% CI: 0.12–4.10, I2 = 18%, p = .04, millimeter). There was a greater improvement in New York Heart Association function class with LBBP (MD: 0.37, 95% CI: 0.05–0.68, I2 = 61%, p = .02). LBBP was also associated with a lower risk of a composite of heart failure hospitalizations (HFH) and all‐cause mortality (RR: 0.48, 95% CI: 0.25–0.90, I2 = 0%, p = .02) driven by reduced HFH (RR: 0.39, 95% CI: 0.19–0.82, I2 = 0%, p = .01). However, all‐cause mortality rates were low in both groups (1.52% vs. 1.13%) and similar (RR: 0.98, 95% CI: 0.21–4.68, I2 = 0%, p = .87).ConclusionThis meta‐analysis of primarily nonrandomized studies suggests that LBBP is associated with a greater improvement in left ventricular systolic function and a lower rate of HFH compared to BVP. There was uniformity of these findings in all of the included studies. However, it would be premature to conclude based solely on the current meta‐analysis alone, given the limitations stated. Dedicated, well‐designed, randomized controlled trials and observational studies are needed to elucidate better the comparative long‐term efficacy and safety of LBBP CRT versus BIV CRT.

AbstractBeta‐site amyloid precursor protein (APP)‐cleaving enzyme 2 (BACE2) is highly expressed in cerebrovascular endothelium. Notably, BACE2 is one of the most downregulated genes in cerebrovascular endothelium derived from patients with Alzheimer's disease. The present study was designed to determine the role of BACE2 in control of expression and function of endothelial nitric oxide synthase (eNOS). Genetic downregulation of BACE2 with small interfering RNA (BACE2siRNA) in human brain microvascular endothelial cells (BMECs) significantly decreased expression of eNOS and elevated levels of eNOS phosphorylated at threonine residue Thr495, thus leading to reduced production of nitric oxide (NO). BACE2siRNA also suppressed expression of APP and decreased production and release of soluble APPα (sAPPα). In contrast, adenovirus‐mediated overexpression of APP increased expression of eNOS. Consistent with these observations, nanomolar concentrations of sAPPα and APP 17mer peptide (derived from sAPPα) augmented eNOS expression. Further analysis established that γ‐aminobutyric acid type B receptor subunit 1 and Krüppel‐like factor 2 may function as downstream molecular targets significantly contributing to BACE2/APP/sAPPα‐induced up‐regulation of eNOS. In agreement with studies on cultured human endothelium, endothelium‐dependent relaxations to acetylcholine and basal production of cyclic GMP were impaired in cerebral arteries of BACE2‐deficient mice. We propose that in the brain blood vessels, BACE2 may function as a vascular protective protein.image