Citations

Study Design: Case Series and Technical Note, Objective: UBS has been extensively used in open surgery. However, the use of UBS during UBESS has not been reported in the literature. The aim of this study was to describe a new spinal surgical technique using an ultrasonic bone scalpel (UBS) during unilateral biportal endoscopic spine surgery (UBESS) and to report the preliminary results of this technique. Methods: We enrolled patients diagnosed with lumbar spinal stenosis who underwent single-level UBESS. All patients were followed up for more than 12 months. A unilateral laminotomy was performed after bilateral decompression under endoscopy. We used the UBS system after direct visualization of the target for a bone cut. We evaluated the demographic characteristics, diagnosis, operative time, and estimated blood loss of the patients. Clinical outcomes included the visual analog scale (VAS), the Oswestry Disability Index (ODI), the modified MacNab criteria, and postoperative complications. Results: A total of twenty patients (five males and fifteen females) were enrolled in this study. The mean follow-up period was 13.2 months (range 12–17 months). The VAS score, ODI, and modified MacNab criteria classification improved after the surgery. A minimal mean blood loss of 22.1 mL was noted during the operation. Only one patient experienced neuropraxia, which resolved within 2 weeks. There was no durotomy, iatrogenic pars fracture, or infection. Conclusions: In conclusion, our study represents the first report of the use of UBS during UBESS. Our findings demonstrate that this technique is safe and efficient, with improved clinical outcomes and minimal complications. These preliminary results warrant further investigation through larger clinical studies with longer follow-up periods to confirm the effectiveness of this technique in the treatment of lumbar spinal stenosis.

Abstract Summary We recently introduced the Gut Microbiome Wellness Index (GMWI), a stool metagenome-based indicator for assessing health by determining the likelihood of disease given the state of one’s gut microbiome. The calculation of our wellness index depends on the relative abundances of health-prevalent and health-scarce species. Encouragingly, GMWI has already been utilized in various studies focusing on differences in the gut microbiome between cases and controls. Herein, we introduce the GMWI-webtool, a user-friendly browser application that computes GMWI, health-prevalent/-scarce species’ relative abundances, and α-diversities from stool shotgun metagenome taxonomic profiles. Users of our interactive online tool can visualize their results and compare them side-by-side with those from our pooled reference dataset of metagenomes, as well as export data in.csv format and high-resolution figures. Availability and implementation GMWI-webtool is freely available here: https://gmwi-webtool.github.io/. Supplementary information Supplementary data are available at Bioinformatics online.

INTRODUCTION: Early-onset colorectal cancer diagnosed before the age of 50 years has been increasing. Likely reflecting the pathogenic role of the intestinal microbiome, which gradually changes across the entire colorectal length, the prevalence of certain tumor molecular characteristics gradually changes along colorectal subsites. Understanding how colorectal tumor molecular features differ by age and tumor location is important in personalized patient management. METHODS: Using 14,004 cases with colorectal cancer including 3,089 early-onset cases, we examined microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and KRAS and BRAF mutations in carcinomas of the cecum, ascending colon, transverse colon, descending colon, sigmoid colon, and rectum and compared early-onset cases with later-onset cases. RESULTS: The proportions of MSI-high, CIMP-high, and BRAF -mutated early-onset tumors were lowest in the rectum (8.8%, 3.4%, and 3.5%, respectively) and highest in the ascending colon (46% MSI-high; 15% CIMP-high) or transverse colon (8.6% BRAF -mutated) (all P trend <0.001 across the rectum to ascending colon). Compared with later-onset tumors, early-onset tumors showed a higher prevalence of MSI-high status and a lower prevalence of CIMP-high status and BRAF mutations in most subsites. KRAS mutation prevalence was higher in the cecum compared with that in the other subsites in both early-onset and later-onset tumors ( P < 0.001). Notably, later-onset MSI-high tumors showed a continuous decrease in KRAS mutation prevalence from the rectum (36%) to ascending colon (9%; P trend <0.001), followed by an increase in the cecum (14%), while early-onset MSI-high cancers showed no such trend. DISCUSSION: Our findings support biogeographical and pathogenic heterogeneity of colorectal carcinomas in different colorectal subsites and age groups.

256 Background: Current staging for colon cancer utilizing the American Joint Committee on Cancer TNM framework stratifies disease into groups according to how advanced the disease is and provides important standardized, individual prognostic information. Ideally, staging systems should exhibit hierarchical logic, with increasing stage reflecting worse prognosis. We sought to evaluate hierarchy within the 8th edition AJCC staging system for colon cancer. Methods: All patients with primary colon (including rectosigmoid) cancer diagnosed 2010-2017 were identified from the National Cancer Database (NCDB). Patients were only included if they carried a histologic diagnosis of invasive primary (non-recurrent) cancer, underwent radical surgery, and had complete pathologic staging data (T, N, M category data). Patients with missing follow-up data were excluded. Kaplan-Meier curves were used to assess overall survival by AJCC 8th edition pathologic summary stage group to determine whether staging was hierarchical for colon cancer. Multivariable modeling and log likelihood ratio test was then used to identify relative contributions of T and N variables to overall survival. Results: Among 270,584 colon cancer patients, pathologic staging was noted to be hierarchical by T category alone and by N category alone. However, summary staging was non-hierarchical in both instances. Multivariable modeling confirmed the AJCC non-hierarchy issue (colon HRs: 1, 1.54, 2.62, 2.60, 1.02, 2.15, and 4.38 for stage 1 as reference, 2a, 2b, 2c, 3a, 3b, 3c respectively). Multivariable modeling demonstrated that high T category (T4a, T4b) conferred the greatest risk of mortality based on hazard ratio (T4a HR 2.76, T4b HR 3.04), while high T category as well as high N category (N2a, N2b) contributed substantially to the survival model based on z-score. Further modeling assessing the predictive power of T and N category with respect to overall survival demonstrated that T category more strongly predicted overall survival than N category in colon cancer (likelihood chi-square test statistic pT:7009 vs pN:3586). Conclusions: Hierarchy in survival based on AJCC summary stage was not observed for patients with stage II-III colon cancer resulting in a paradoxical better observed survival with some stage III cancer subgroups compared to stage II cancer subgroups. High T category appears to more significantly impact survival than N category for patients with N0-N1 disease, while high N category appears more important for patients with T1-3 disease. Future revisions of the AJCC staging system should account for the differential impact of T and N category identified herein to more accurately confer prognostic information.

AbstractBackgroundAs gene‐targeted therapies are increasingly being developed for Parkinson's disease (PD), identifying and characterizing carriers of specific genetic pathogenic variants is imperative. Only a small fraction of the estimated number of subjects with monogenic PD worldwide are currently represented in the literature and availability of clinical data and clinical trial‐ready cohorts is limited.ObjectiveThe objectives are to (1) establish an international cohort of affected and unaffected individuals with PD‐linked variants; (2) provide harmonized and quality‐controlled clinical characterization data for each included individual; and (3) further promote collaboration of researchers in the field of monogenic PD.MethodsWe conducted a worldwide, systematic online survey to collect individual‐level data on individuals with PD‐linked variants in SNCA, LRRK2, VPS35, PRKN, PINK1, DJ‐1, as well as selected pathogenic and risk variants in GBA and corresponding demographic, clinical, and genetic data. All registered cases underwent thorough quality checks, and pathogenicity scoring of the variants and genotype–phenotype relationships were analyzed.ResultsWe collected 3888 variant carriers for our analyses, reported by 92 centers (42 countries) worldwide. Of the included individuals, 3185 had a diagnosis of PD (ie, 1306 LRRK2, 115 SNCA, 23 VPS35, 429 PRKN, 75 PINK1, 13 DJ‐1, and 1224 GBA) and 703 were unaffected (ie, 328 LRRK2, 32 SNCA, 3 VPS35, 1 PRKN, 1 PINK1, and 338 GBA). In total, we identified 269 different pathogenic variants; 1322 individuals in our cohort (34%) were indicated as not previously published.ConclusionsWithin the MJFF Global Genetic PD Study Group, we (1) established the largest international cohort of affected and unaffected individuals carrying PD‐linked variants; (2) provide harmonized and quality‐controlled clinical and genetic data for each included individual; (3) promote collaboration in the field of genetic PD with a view toward clinical and genetic stratification of patients for gene‐targeted clinical trials. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Abstract Background The role of ovulation in epithelial ovarian cancer (EOC) is supported by the consistent protective effects of parity and oral contraceptive use. Whether these factors protect through anovulation alone remains unclear. We explored the association between lifetime ovulatory years (LOY) and EOC. Methods LOY was calculated using 12 algorithms. Odds ratios (ORs) and 95% confidence intervals (CIs) estimated the association between LOY or LOY components and EOC among 26 204 control participants and 21 267 case patients from 25 studies. To assess whether LOY components act through ovulation suppression alone, we compared beta coefficients obtained from regression models with expected estimates assuming 1 year of ovulation suppression has the same effect regardless of source. Results LOY was associated with increased EOC risk (OR per year increase = 1.014, 95% CI = 1.009 to 1.020 to OR per year increase = 1.044, 95% CI = 1.041 to 1.048). Individual LOY components, except age at menarche, also associated with EOC. The estimated model coefficient for oral contraceptive use and pregnancies were 4.45 times and 12- to 15-fold greater than expected, respectively. LOY was associated with high-grade serous, low-grade serous, endometrioid, and clear cell histotypes (ORs per year increase = 1.054, 1.040, 1.065, and 1.098, respectively) but not mucinous tumors. Estimated coefficients of LOY components were close to expected estimates for high-grade serous but larger than expected for low-grade serous, endometrioid, and clear cell histotypes. Conclusions LOY is positively associated with nonmucinous EOC. Differences between estimated and expected model coefficients for LOY components suggest factors beyond ovulation underlie the associations between LOY components and EOC in general and for non-HGSOC.

AbstractATP6AP1‐CDG is an X‐linked disorder typically characterized by hepatopathy, immunodeficiency, and an abnormal type II transferrin glycosylation pattern. Here, we present 11 new patients and clinical updates with biochemical characterization on one previously reported patient. We also document intrafamilial phenotypic variability and atypical presentations, expanding the symptomatology of ATP6AP1‐CDG to include dystonia, hepatocellular carcinoma, and lysosomal abnormalities on hepatic histology. Three of our subjects received successful liver transplantation. We performed N‐glycan profiling of total and fractionated plasma proteins for six patients and show associations with varying phenotypes, demonstrating potential diagnostic and prognostic value of fractionated N‐glycan profiles. The aberrant N‐linked glycosylation in purified transferrin and remaining plasma glycoprotein fractions normalized in one patient post hepatic transplant, while the increases of Man4GlcNAc2 and Man5GlcNAc2 in purified immunoglobulins persisted. Interestingly, in the single patient with isolated immune deficiency phenotype, elevated high‐mannose glycans were detected on purified immunoglobulins without glycosylation abnormalities on transferrin or the remaining plasma glycoprotein fractions. Given the diverse and often tissue specific clinical presentations and the need of clinical management post hepatic transplant in ATP6AP1‐CDG patients, these results demonstrate that fractionated plasma N‐glycan profiling could be a valuable tool in diagnosis and disease monitoring.

AbstractStudy ObjectiveIn critically ill patients, adequacy of early antibiotic exposure has been incompletely evaluated. This study characterized factors associated with inadequate cefepime exposure in the first 24 h of critical illness.DesignProspective cohort study.SettingAcademic Medical Center.PatientsCritically ill adults treated with cefepime. Patients with acute kidney injury or treated with kidney replacement therapy or extracorporeal membrane oxygenation were excluded.InterventionNone.MeasurementsA nonlinear mixed‐effects pharmacokinetic (PK) model was developed to estimate cefepime concentrations for each patient over time. The percentage of time the free drug concentration exceeded 8 mg/L during the first 24 h of therapy was calculated (%ƒT>8; appropriate for the susceptible breakpoint for Pseudomonas aeruginosa). Factors predictive of low %ƒT>8 were explored with multivariable regression.Main ResultsIn the 100 included patients, a one‐compartment PK model was developed with first‐order elimination with covariates for weight and estimated glomerular filtration rate based on creatinine and cystatin C (eGFRSCr‐CysC). The median (interquartile range) %ƒT>8 for cefepime in the first 24 h of therapy based on this model was 85% (66%, 100%). Less than 100% ƒT>8 during first 24 h of therapy occurred in 70 (70%) individuals. Lower Sequential Organ Failure Assessment score (p = 0.032) and higher eGFRSCr‐CysC (p < 0.001) predicted a lower %ƒT>8. Central nervous system infection source was protective (i.e., associated with a higher %ƒT>8; p = 0.008).ConclusionsDuring early critical illness, cefepime concentrations were inadequate in a significant proportion of patients. Antimicrobial optimization is needed to improve the precision of pharmacotherapy in the critically ill patients.

Abstract Aims To investigate whether left arterial reservoir strain (LASr) could predict new-onset atrial fibrillation (NOAF) in patients with light-chain-type cardiac amyloidosis (ALCA). Methods and results This study enrolled 427 patients with CA from two tertiary centres between 2005 and 2019. LASr was measured using a vendor-independent analysis programme. The primary outcome was NOAF. A total of 287 patients with ALCA were included [median age 63.0 (56.0–70.0) years, 53.3% male]. The median LASr was 13.9% (10.5–20.8%). During the median follow-up of 0.85 years, AF occurred in 34 patients (11.8%). In the receiver operating characteristics curve analysis, the optimal cut-off of LASr for predicting NOAF was 14.4%. Patients with LASr ≤14.4% had a higher risk of NOAF than those with LASr &gt;14.4% (18.1% vs. 5.1%, P &lt; 0.010). In the multivariate analysis adjusting for confounding factors, including left arterial volume index and left ventricular global longitudinal strain (LV-GLS), higher LASr (%) was independently associated with lower risk for NOAF [adjusted hazard ratio (aHR): 0.936, 95% confidence interval (95% CI): 0.879–0.997, P = 0.039]. Furthermore, LASr ≤14.4% was an independent predictor for NOAF (aHR: 3.370, 95% CI: 1.337–8.492, P = 0.010). This remained true after accounting for all-cause death as a competing risk. Compared with Model 1 (LV-GLS) and Model 2 (LV-GLS plus LAVI), Model 3, including LASr showed a better reclassification ability for predicting NOAF (net reclassification index = 0.735, P &lt; 0.001 compared with Model 1; net reclassification index = 0.514, P = 0.003 compared with Model 2). Conclusion LASr was an independent predictor of NOAF in patients with ALCA.