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Purpose: To explore how the change-point method can be used to analyze complex longitudinal data and detect when meaningful changes (change points) have occurred during rehabilitation. Method: This design is a prospective single-case observational study of a football player in a professional club who sustained an acute lower-limb muscle injury during high-speed running in training. The rehabilitation program was entirely completed in the football club under the supervision of the club's medical team. Four wellness metrics and 5 running-performance metrics were collected before the injury and until the player returned to play. Results: Data were collected over 130 days. In the univariate analysis, the change points for stress, sleep, mood, and soreness were located on days 30, 47, 50, and 50, respectively. The change points for total distance, acceleration, maximum speed, deceleration, and high-speed running were located on days 32, 34, 37, 41, and 41, respectively. The multivariate analysis resulted in a single change point for the wellness metrics and running-performance metrics, on days 50 and 67, respectively. Conclusions: The univariate approach provided information regarding the sequence and time point of the change points. The multivariate approach provided a common change point for multiple metrics, information that would benefit clinicians to have a broad overview of the changes in the rehabilitation process. Clinicians may consider the change-point method to integrate and visualize data from multiple sources to evaluate athletes' progression along the return-to-sport continuum. [ABSTRACT FROM AUTHOR]

Context: The hip adductor and abductor muscles play vital roles as stabilizers in the lower-extremity. Their activation during soccer-specific actions is essential, but local muscular fatigue can hinder athletic performance and increase the risk of injury. Design: This study aimed to observe the variations in frontal plane hip strength in female college soccer players before and after a high-workload soccer-specific training session. Furthermore, the study sought to compare the relative changes in hip strength with the internal and external load measures obtained during that session. Methods: Twenty female college soccer players participated in a retrospective observational study. Isometric hip adductor and abductor strength were measured before and after a training session in the college spring season. Measurements were taken with a handheld dynamometer (MicroFET 2) while the players were supine. Global positioning system sensors (Catapult Vector S7), commonly worn by players during training sessions and competitive matches, were used to measure external and internal loads. Statistical analyses were performed using paired samples t test to assess hip adductor and abductor strength changes before and after the training session. Spearman rank was used to identify correlation coefficients between global positioning system data and isometric hip strength. Results: The findings revealed significant decreases in the strength of the right hip adduction (P =.012, −7% relative change), right abduction (P =.009, −7.6% relative change), and left abduction (P =.016, −4.9% relative change) after the training session. Furthermore, relative decreases in hip isometric adduction and abduction strength are related to the distance covered at high speeds. Conclusion: The results of this study highlight that hip isometric adduction and abduction strength tend to decrease after exposure to high workloads during soccer-specific training. [ABSTRACT FROM AUTHOR]

Purpose: To compare the standard Yo-Yo intermittent recovery (IR) test and an agility Yo-Yo IR test with a higher number of change-of-direction movements to cardiorespiratory match performance. Methods: The study included 11 professional male handball players (age 24.5 [4.6] y) of a German second-league team. The performance parameters of the players of the seasons 2016–17 to 2018–19 were analyzed. The Yo-Yo IR test was compared to a Yo-Yo IR test with multiple multidirectional changes of direction in response to visual stimuli, which was conducted on a SpeedCourt (Yo-Yo SC IR). Peak oxygen uptake (VO2peak) and maximum heart rate (HRmax) were measured. Between-methods differences of individual athletes were quantified with Bland–Altman plots. Results: HRmax was not statistically different during the Yo-Yo SC IR test compared to the Yo-Yo IR test (181 [10] vs 188 [8] beats·min−1; P =.16). Agreement between the 2 tests was moderate for HRmax and good for heart rates >180 beats·min−1. Mean average VO2peak was 51.7 (3.9) and 50.9 (2.8) mL·min–1·kg–1 for the Yo-Yo SC IR test and the Yo-Yo IR test (P =.693), respectively. Conclusions: A Yo-Yo test with multidirectional changes of direction in response to visual stimuli yielded good agreement with the frequently used linear running tests and can be used to assess players' VO2peak. The HRmax achieved during this test should be used with caution. [ABSTRACT FROM AUTHOR]

This retrospective study reports on the survival of two-piece angulated prosthetic platform (APP) implants consecutively placed at a specialist periodontics clinic with a mean follow-up of 28.2 ± 15.6 months (range: 4.0 to 71.0). For 183 returning patients who received 239 implants, the survival rates at follow-up (up to 71 months) were 99.2% and 91.1% at the patient and implant levels, respectively. A majority of patients were nonsmokers and did not have diabetes, with a quarter having a history of treated periodontitis. Eighty percent of patients received a single APP implant. Of the implants, 63% supported a single crown, 28% a fixed partial denture, and 9% a fixed complete denture. Nearly all implants were placed either at tooth extraction or after complete bone healing, in approximately equal numbers. Of the implant sites, approximately 75% received bone grafting, with approximately 25% receiving adjunct soft tissue grafting. For 210 surviving and restored implants with satisfactory intraoral radiographs taken at the last recall (mean follow-up: 28.4 ± 15.5 months; range: 4.0 to 71.0 months), the mean radiographic bone levels were -0.70 ± 0.87 mm (range: -3.60 to 2.15 mm). The results demonstrated clinically successful use of this unique geometry implant for multiple applications with acceptable short- to medium-term clinical outcomes. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the clinical effectiveness of regenerative treatment of intrabony defects in combination with consecutive orthodontic therapy with clear aligners in stage IV (type 2) periodontitis. Method and materials: Ten patients with a total of 103 intrabony defects were analyzed after regenerative surgery using collagen-deproteinized bovine bone mineral with or without collagen membrane or enamel matrix derivative followed by orthodontic therapy with clear aligners. Changes in radiographic bone level and probing pocket depths were evaluated after 1 year (T1) and at final splinting (T2) after orthodontic tooth movement. Results: Mean radiographic bone level gain was significant, with 2.13 ± 1.64 mm at T1 and 3.02 ± 2.00 mm at T2. Mean probing pocket depth was significantly reduced from 5.40 ± 1.80 mm at baseline to 3.78 ± 1.73 mm at T1, and remained stable with 3.73 ± 1.70 mm at T2. Pocket closure (≤ 4 mm probing pocket depth) was accomplished in 76% of all defects. Tooth loss amounted to 2.9%. Conclusion: Within the limitations of the retrospective study design, the findings suggest that the interdisciplinary treatment of periodontitis stage IV by regenerative periodontal surgery and consecutive orthodontic therapy with clear aligners can lead to favorable results. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to describe the day-by-day training and racing characteristics in preparation for the Giro d'Italia of 1 world-class road cyclist who achieved a place on the podium in the final general classification of the Giro d'Italia. Methods: Day-by-day power meter training and racing data of 1 study subject (road cyclist; age 25 y; relative maximum oxygen consumption 81 mL·min−1·kg−1; relative 20-min record power output 6.6 W·kg−1) covering the 152 days leading up to the podium in the Giro d'Italia final general classification were retrospectively analyzed. Daily load, daily volume, and intensity distribution were considered. Results: During training a pattern alternating "hard days" versus "easy days" was observed, as significant amounts of medium or high intensity, or load, were not performed for more than 2 consecutive days This pattern was achieved combining high volume (>4 h) with a significant amount of medium and high intensity within the same training sessions. During training, when training load and intensity increased, the density of "easy days" augmented. In 1-week stage races and the Giro d'Italia, 3 to 8 consecutive days with significant amounts of medium and high intensity were performed. A high number of training sessions with small amounts of medium- and high-intensity volume was observed: 38 days accumulating 3 to 10 minutes at medium intensity and 29 days spending 1 to 9 minutes at high intensity. Conclusion: These data provide novel insights about the day-by-day periodization strategies leading to a top 3 in the Giro d'Italia general classification. [ABSTRACT FROM AUTHOR]

Objective: This retrospective study analyzed radiographic bone levels of 10,871 dental implants in a cohort of 4,247 patients over a 22-year period. The objectives of the study were to assess and explore risk factors associated with the radiographic bone level of dental implants. Method and materials: A longitudinal observational cohort study based on data collected from 1995 to 2019 was conducted on implants placed by a single periodontist. Inclusion criteria included both partially and fully edentulous sites. Exclusion criteria were patients who were considered ASA 3 or greater. Information on medical and dental status prior to implant placement such as diabetes and smoking were included in the analysis. Implant factors such as the implant characteristics (length and diameter) and surgical site were recorded. The outcome assessed was the prevalence of bone loss around implants and any associative factors related to the bone loss. Results: Overall, dental implants lost an average of 0.05 ± 0.38 mm of bone 2 to 3 years after placement and 0.21 ± 0.64 mm 8 years after placement. The soft tissue condition was evaluated using the Implant Mucosal Index (IMI), and bone loss around dental implants was significantly higher when bleeding on probing was multi-point and moderate, multi-point and profuse, and when infection with suppuration was recorded. The mean difference in bone level between smokers and nonsmokers was 0.26 mm (P < .01) over a 4-year period. A mean difference of 0.10 mm (P = .04) in bone loss over 4 years was found between those with an autoimmune disease compared to those without. The diameter of the implant and immediate loading of the dental implant did not influence the radiographic bone levels over time. Conclusions: This large dataset of dental implants highlights predictive risk factors for bone loss around dental implants and the impact these risk factors have on the implant bone level. Consideration of these risk factors by both the dental team and the patient prior to dental implant placement will promote success of the treatment. [ABSTRACT FROM AUTHOR]

Objective: The evidence base for the use of space maintainers is relatively sparce despite being used for decades after the premature loss of primary molars. This study aims to increase the dental evidence base via investigating retrospectively the success rates of prefabricated fixed and removable space maintainers inserted from 2019 to 2021 and followed up until February 2023 at a specialized university clinic and to identify reasons for any reported minor and major failure. The authors hypothesized that there is no significant difference in failure rates between fixed and removable space maintainers inserted after the premature loss of a single primary molar per quadrant. Method and materials: Patients' digital records were searched yielding 645 space maintainers. After the application of inclusion criteria, 157 (67%) fixed prefabricated space maintainers in 112 children and 77 (33%) removable space maintainers in 61 children were analyzed for an average of 18.4 ± 9.5 months. Results: Kaplan-Meier survival analysis with Mantel-Cox statistics showed an overall cumulative survival time of 31.6 months (SE = 1.15, 95% CI = 29.4 to 33.9). Major failure occurred significantly more in removable maintainers (n = 40/67, 59.7%), mostly due to loss of the appliance, compared to fixed space maintainers (n = 27/67, 40.3%; P < .001). The present study indicates that space maintainers were mainly placed in young children with high caries experience, where treatment was mostly possible using advanced behavior management. Conclusions: Fixed space maintainers had a significantly lower failure rate than their removable counterpart. However, both require continual repairs, preservation, or even replacement till the eruption of the permanent tooth. [ABSTRACT FROM AUTHOR]

Disruptions in gait function are common after concussion in adolescents; however, the neuromotor control deficits driving these gait disruptions are not well known. Fifteen concussed (age mean [SD]): 17.4 [0.6], 13 females, days since injury: 26.3 [9.9]) and 17 uninjured (age: 18.0 [0.7], 10 females) adolescents completed 3 trials each of single-task gait and dual-task gait (DT). During DT, participants simultaneously walked while completing a serial subtraction task. Gait metrics and variability in instantaneous mean frequency in lower extremity muscles were captured by inertial sensors and surface electromyography, respectively. A 2-way analysis of covariance was used to compare gait metrics across groups and conditions. Functional principal components analysis was used to identify regions of variability in instantaneous mean frequency curves. Functional principal component scores were compared across groups using a Welch statistic. Both groups displayed worse performance on gait metrics during DT condition compared to single-task, with no differences between groups (P <.001). Concussed adolescents displayed significantly greater instantaneous mean frequency, indicated by functional principal component 1, in the tibialis anterior, biceps femoris, and semitendinosus (P <.05) during single-task and DT compared with uninjured adolescents. Our observations suggest that concussed adolescents display inefficient motor unit recruitment lasting longer than 2 weeks following injury, regardless of the addition of a secondary task. [ABSTRACT FROM AUTHOR]

BACKGROUND: In 2023 alone, its estimated that over 64,000 patients will be diagnosed with PDAC and more than 50,000 patients will die of the disease. Current guidelines recommend neoadjuvant therapy for patients with borderline resectable and locally advanced PDAC, and data is emerging on its role in resectable disease. Neoadjuvant chemotherapy may increase the number of patients able to receive complete chemotherapy regimens, increase the rate of microscopically tumor-free resection (R0) margin, and aide in identifying unfavorable tumor biology. To date, this is the largest study to examine surgical outcomes after long-duration neoadjuvant chemotherapy for PDAC. METHODS: Retrospective analysis of single-institution data. RESULTS: The routine use of long-duration therapy in our study (median cycles: FOLFIRINOX = 10; gemcitabine-based = 7) is unique. The majority (85%) of patients received FOLFIRINOX without radiation therapy; the R0 resection rate was 76%. Median OS was 41 months and did not differ significantly among patients with resectable, borderline-resectable, or locally advanced disease. CONCLUSIONS: This study demonstrates that in patients who undergo surgical resection after receipt of long-duration neoadjuvant FOLFIRINOX therapy alone, survival outcomes are similar regardless of pretreatment resectability status and that favorable surgical outcomes can be attained.

Ewing sarcoma (ES) is an uncommon mesenchymal neoplasm that typically develops as a bone mass, although up to 30% arise in extraskeletal sites. ES of the gastrointestinal (GI) and hepatobiliary tract is rare and may be misdiagnosed as other, more common neoplasms that occur in these sites. However, the correct classification of extraskeletal ES is important for timely clinical management and prognostication. We reviewed our experience of ES in the GI and hepatobiliary tract in order to further highlight the clinicopathologic features of these neoplasms and document the potential for misdiagnosis in this setting. The archives and consultation files of 6 academic institutions were retrospectively queried for cases of ES occurring in the GI and hepatobiliary tract. The histologic slides and ancillary studies were reviewed and clinical data were retrieved for each case through the electronic medical records, when available. Twenty-three patients with ES in the GI and/or hepatobiliary tract were identified from 2000 to 2022. Of these, 11 were women and 12 were men with a median age of 38 years (range, 2 to 64). Tumor locations included the pancreas (n=5), liver (n=2), stomach (n=3), colorectum (n=3), and small intestine (n=5), as well as tumors involving multiple organs, pelvis and retroperitoneum (n=5). Tumor size varied between 2 cm and 18 cm. Twenty were primary and 3 were metastases. Of the 23 cases, only 17% were initially diagnosed as ES. The most common misdiagnoses involved various forms of neuroendocrine neoplasia due to expression of synaptophysin and other neuroendocrine markers (22%). A wide variety of diagnoses including GI stromal tumor was considered due to aberrant CD117 expression (4%). The diagnosis of ES was ultimately confirmed by detection of the EWSR1 rearrangement in 22 cases. The remaining case was diagnosed using traditional immunohistochemistry. Follow-up information was available in 20 cases, with follow-up time varying between 2 and 256 months. Six patients with follow-up died of disease between 6 and 60 months following initial presentation. Our data indicate ES in the GI and hepatobiliary tract is commonly misdiagnosed leading to a delay in therapy. In light of the attendant therapeutic and prognostic implications, ES should be considered in the differential diagnosis of any GI or hepatobiliary tumor with epithelioid and/or small round cell morphology.

Micro-ultrasound has recently been introduced as a low-cost alternative to multi-parametric MRI for imaging prostate cancer. Early clinical studies have demonstrated promising results; however, robust validation via comparison with whole-mount pathology has yet to be achieved. Due to micro-ultrasound probe design and tissue deformation during scanning, it is difficult to accurately correlate micro-ultrasound imaging planes with ground truth whole-mount pathology slides. In this study, we developed a multi-step methodology to co-register micro-ultrasound and MRI to whole-mount pathology. The three-step process had a registration error of 3.90 ± 0.11 mm and consists of: (1) micro-ultrasound image reconstruction, (2) 3D landmark registration of micro-ultrasound to MRI, and (3) 2D capsule registration of MRI to whole-mount pathology. This process was then used in a preliminary reader study to compare the diagnostic accuracy of micro-ultrasound and MRI in 15 patients who underwent radical prostatectomy for prostate cancer. Micro-ultrasound was found to have equivalent performance to retrospective MRI review for index lesion detection (91.7% vs. 80%), while demonstrating an increased detection of tumor extent (52.5% vs. 36.7%) with similar false positive regions-of-interest (38.3% vs. 40.8%). Prospective MRI review had reduced detection of index lesions (73.3%) and tumor extent (18.9%) but improved false positive regions-of-interest (22.7%) relative to micro-ultrasound and retrospective MRI. Further evaluation is needed with a larger sample size.

Minimal residual disease (MRD) assessment is a known surrogate marker for survival in multiple myeloma (MM). Here, we present a single institutions experience assessing MRD by NGS of Ig genes and the long-term impact of depth of response as well as clonal diversity on the clinical outcome of a large population of MM patients; 482 MM patients at the University of California, San Francisco (UCSF) diagnosed from 2008 to 2020 were analyzed retrospectively. MRD assessment was performed by NGS. PFS curves were plotted by the Kaplan-Meier method. In the newly diagnosed group, 119 of 304, achieved MRD negativity at the level of 10-6 at least once. These patients had a prolonged PFS versus patients who were persistently MRD positive at different levels (p > 0.0001). In the relapsed disease group, 64 of 178 achieved MRD negativity at 10-6, and PFS was prolonged versus patients who remained MRD positive (p = 0.03). Three categories of MRD dynamics were defined by artificial intelligence: (A) patients with ≥3 consistently MRD negative samples, (B) patients with continuously declining but detectable clones, and (C) patients with either increasing or a stable number of clones. Groups A and B had a more prolonged PFS than group C (p

PURPOSE: In addition to the existing biomarkers HER2 and PD-L1, FGFR2b has become an area of interest for the development of new targeted-based treatment. Given that clinical evaluation of FGFR2 targeted therapy is underway, we sought to elucidate the genomic landscape of FGFR2amp in gastroesophageal cancer (GEC) using a circulating tumor DNA (ctDNA) platform. MATERIALS AND METHODS: We retrospectively evaluated the Guardant Health database from 2017 to 2022 for patients with GECs with Guardant360 ctDNA next-generation sequencing (NGS) performed. We assessed co-occurring genetic alterations for patients who harbored FGFR2amp versus FGFR2null. We also explored real-world evidence database with Guardant Health, publicly available genomic databases (MSK cohort using cBioPortal), and pooled clinical data from large-volume cancer centers for FGFR2amp GECs. RESULTS: Less than 4% of patients with GEC in the Guardant Health database were identified to be FGFR2amp. The most commonly co-occurring gene mutations were TP53, CTNNB1, CDH1, and RHOA. Upon interrogation of the MSK cohort, these same genes were not significant on tissue NGS in the FGFR2amp cohort of GEC. In the pooled institutional cohort, we noted that FGFR2amp tumors were most commonly involving the gastroesophageal junction (GEJ). The overall survival of these patients was noted at 13.1 months. CONCLUSION: FGFR2 is a validated target in GECs, and the contexture of FGFR2amp will be important in defining patient subgroups with responses to FGFR2-directed therapy. Using ctDNA to provide a more detailed genomic landscape in patients with GECs will allow the advancement of targeted therapy in the near future for these aggressive cancers.

PURPOSE: To evaluate Humphrey Visual Field (HVF) test reliability and its associated risk factors in children with glaucoma or glaucoma suspect. DESIGN: Retrospective cohort study. METHODS: None. SETTING: Single-center childhood glaucoma clinic. PATIENT POPULATION: One hundred thirty-six patients aged ≤18 years with glaucoma/glaucoma suspect, and least 1 completed 24 to 2 HVF test between 2018 and 2023. OBSERVATION PROCEDURE: Demographic and clinical characteristics including age, primary language, visual acuity (VA), and glaucoma diagnosis were extracted from electronic health records. MAIN OUTCOME MEASURES: HVF 24 to 2 testing metrics, including FP, FN, and FL. Tests were defined as reliable using manufacturer guidelines of ≤33% FP, ≤33% FN, and ≤20% FL. For each patient, a reliability score was calculated as the percentage of reliable tests among all tests completed. A multivariable logistic regression model was used to determine factors associated with test-level reliability (yes/no). A multivariable linear regression model was used to determine factors associated with patient-level reliability score. RESULTS: Among 634 HVFs from 136 patients (Mean ± SD age at first test 12.0 ± 3.2 years, 47.8% female), 51.3% were reliable. Older age, better baseline VA, and English as primary language were associated with greater odds of test-level reliability (P < .04). Mean ± SD patient-level reliability score was 51.7 ± 38.1%. Older age at first clinic visit, better baseline VA, and English as primary language were associated with higher reliability scores (all P < .02), and number of prior VF tests was not (P = .56). CONCLUSIONS: Younger age, worse visual acuity, and non-English as primary language were associated with decreased reliability and should be considered when interpreting VF testing in children. A significant learning effect was not observed with repeated testing.

BackgroundIncisional hernia (IH) is a known complication after colorectal surgery. Despite advances in minimally invasive surgery, colorectal surgery still requires extraction sites for specimen retrieval, increasing the likelihood of postoperative IH development. The objective of this study is to determine the effect of specimen extraction site on the rate of IH after minimally invasive right-sided colectomy for patients with available imaging.Study designThis is a retrospective multi-institutional cohort study at 2 large academic medical centers in the US. Adults who underwent right-sided minimally invasive colectomy from 2012 to 2020 with abdominal imaging available at least 1 year postoperatively were included in the analysis. The primary exposure was specimen extraction via a midline specimen extraction vs Pfannenstiel specimen extraction. The main outcome was the development of IH at least 1 year postoperatively as visualized on a CT scan.ResultsOf the 341 patients sampled, 194 (57%) had midline specimen extraction and 147 (43%) had a Pfannenstiel specimen extraction. Midline extraction patients were older (66 ± 15 vs 58 ± 16; p < 0.001) and had a higher rate of previous abdominal operation (99, 51% vs 55, 37%, p = 0.01). The rate of IH was higher in midline extraction at 25% (48) compared with Pfannenstiel extraction (0, 0%; p < 0.001). The average length of stay was higher in the midline extraction group at 5.1 ± 2.5 compared with 3.4 ± 3.1 days in the Pfannenstiel extraction group (p < 0.001). Midline extraction was associated with IH development (odds ratio 24.6; 95% CI 1.89 to 319.44; p = 0.004). Extracorporeal anastomosis was associated with a higher IH rate (odds ratio 25.8; 95% CI 2.10 to 325.71; p = 0.002).ConclusionsPatients who undergo Pfannenstiel specimen extraction have a lower risk of IH development compared with those who undergo midline specimen extraction.

A neural network was developed to detect and characterize bowel obstruction, a common cause of acute abdominal pain. In this retrospective study, 202 CT scans of 165 patients with bowel obstruction from March to June 2022 were included and partitioned into training and test data sets. A multi-channel neural network was trained to segment the gastrointestinal tract, and to predict the diameter and the longitudinal position (longitude) along the gastrointestinal tract using a novel embedding. Its performance was compared to manual segmentations using the Dice score, and to manual measurements of the diameter and longitude using intraclass correlation coefficients (ICC). ROC curves as well as sensitivity and specificity were calculated for diameters above a clinical threshold for obstruction, and for longitudes corresponding to small bowel. In the test data set, Dice score for segmentation of the gastrointestinal tract was 78 ± 8%. ICC between measured and predicted diameters was 0.72, indicating moderate agreement. ICC between measured and predicted longitude was 0.85, indicating good agreement. AUROC was 0.90 for detection of dilated bowel, and was 0.95 and 0.90 for differentiation of the proximal and distal gastrointestinal tract respectively. Overall sensitivity and specificity for dilated small bowel were 0.83 and 0.90. Since obstruction is diagnosed based on the diameter and longitude of the bowel, this neural network and embedding may enable detection and characterization of this important disease on CT.

With over 16 million submitted genomic sequences, the SARS-CoV-2 (SC2) virus, the cause of the most recent worldwide COVID-19 pandemic, has become the most sequenced genome of all known viruses, revealing, for example, a vast number of expanding viral lineages. Since the pandemic phase appears to be over, we performed a retrospective re-examination of the demographic grouping pattern and their genomic characteristics during the entire pandemic period up to the peak of the last pandemic wave. For our study, we extracted from the NCBI only unique viral sequences and converted each sequence data to a relational vector, indicating the presence/absence of each variational event compared to a reference sequence. Our study revealed several genomic features that are unexpected or different from those of previous studies. For example, approximately 44,000 variants with unique sequences emerged during the pandemic period; they group into only four major viral-genomic groups and each has a set of mostly unique highly-conserved variant-genotypes (HCVGs); and a small set from the first (ancestral) group was inherited by the three (descendant) groups, suggesting that HCVGs in the next group may be predictable from the current group(s). Such a concept may be potentially important in designing panvalent vaccines against the current and future waves of viral infections.

OBJECTIVE: To evaluate the role of psychosocial well-being on perioperative pain and opioid use among patients with cleft lip and palate (CLP) undergoing alveolar bone grafting (ABG). DESIGN: Retrospective review. SETTING: Tertiary level craniofacial clinic. PARTICIPANTS: 34 patients with CLP (median age: 11.7 years), including 25 (73.5%) unilateral CLP and 9 (26.5%) bilateral CLP, who underwent ABG from 2015 to 2022. INTERVENTIONS: ABG using iliac crest bone graft. Patients were prospectively administered four patient-reported psychosocial instruments from the Patient-Reported Outcomes Measurement Information System. MAIN OUTCOME MEASURES: Perioperative opioid use in morphine equivalent dosage/kilogram, patient-reported pain scores, and length of hospital stay after ABG. RESULTS: Patient-reported anxiety (r = 0.41, p = 0.02) and depressive symptoms (r = 0.35, p = 0.04) correlated to higher perioperative opioid usage. Multivariable regression models including psychosocial scores, total acetaminophen usage, length of surgery, and other simultaneous surgeries were developed for total opioid usage, patient-reported pain, and length of hospital stay. Patient-reported anxiety was independently predictive of higher perioperative opioid use (β=0.36, p = 0.01) and higher pain scores (β=0.39, p = 0.02), but not length of hospital stay. CONCLUSIONS: We identified an association for patient-reported anxiety and perioperative opioid use and pain in a CLP cohort undergoing ABG. Future considerations in preoperative patient and family consultation may be indicated in patients self-reporting higher anxiety in an effort to minimize perioperative opioid usage.

BackgroundTo examine long-term retinal nerve fibre layer thickness (RNFLT) variability and associated clinical factors in African (AD) and European descent (ED) individuals with glaucoma.MethodsThis retrospective cohort study included glaucoma eyes of AD and ED from Diagnostic Innovations in Glaucoma Study/The African Descent and Glaucoma Evaluation Study with ≥4 visits/2 years of follow-up. We calculated optic nerve head RNFLT variability per-examination/visit as the absolute error of its residuals across follow-up. Full, baseline and parsimonious linear-mixed models were fit to evaluate the effects of clinical factors (demographics and ocular characteristics, prior/intervening glaucoma surgeries and cataract extraction (CE), RNFLT thinning rate, scan quality, visit/testing frequency, etc) on RNFLT variability in both races.ResultsThere were 376 and 625 eyes (226 and 349 participants) of AD and ED, and the mean (95% CI) RNFLT variability was 1.62 (1.52, 1.71) µm and 1.42 (1.34, 1.50) µm, respectively (p=0.002). AD and ED had some shared predictors of RNFLT variability, including intraocular pressure fluctuation and scan quality, although the effects varied (p

BACKGROUND: Guidelines recommend dual-energy x-ray absorptiometry (DXA) screening to assess fracture risk and benefit from antiresorptive therapy in men with metastatic hormone-sensitive prostate cancer (mHSPC) on androgen deprivation therapy (ADT). However,

His-bundle pacing has demonstrated feasibility in numerous adult studies to reverse and prevent pacing-induced cardiomyopathy, however, is met with higher capture thresholds with deployment sheaths designed for adults with his-bundles in the typical location. To describe 24 pediatric and adult congenital patients post-physiologic pacing. Patients at the University of Minnesota Masonic Childrens Hospital with congenital complete heart block or congenital heart disease and atrioventricular block presented for pacemaker placement between November 2019 and January 2021. Twenty-four patients had attempted his-bundle placement using either Medtronics C315 or C308 sheaths and 3830 leads except for 3 patients who had Boston Scientifics His system with the Shape 3 sheath and 7842 leads. Twenty-four total patients underwent physiologic pacing (23 his-bundle, 13 female, 11 male) with median age of 14 years (range 8-39 years) with median weight of 51 kg (range 21.2-81 kg) with five right-sided implants performed. Twelve patients had congenital heart disease including atrioventricular canal defects, tetralogy of Fallot, and ventricular septal defect repairs (nine patients with ventricular septal defect repairs). Twelve patients had selective His-bundle pacing (six with congenital heart disease). Median threshold to capture was 0.5 V at 0.4 ms (range 0.4 to 1.1 V at 0.4 ms), impedance 570 ohms (range 456-1140 ohms), and sensing median of 9.7 mV (range 1.5-13.8 mV if present). The median follow-up time was 610 days (range 240-760 days). No complications occurred peri-procedurally or during follow-up. His-bundle pacing is feasible in pediatric and congenital heart disease patients.

OBJECTIVE: To estimate and contrast the relationships between nurse staffing and health outcomes in nursing homes with low and high dementia census, to understand the association of staffing hours with dementia care quality. DATA SOURCES AND STUDY SETTING: A national sample of nursing homes during 2017-2019 (pre-COVID). Data included the Payroll-Based Journal, Medicare Claims, Nursing Home Care Compare, and Long-Term Care Focus. STUDY DESIGN: Retrospective, regression analyses. We estimated separate linear models predicting six long-term facility-level outcomes. Independent variables included staffing hours per resident-day (HPRD) interacted with the facility percentage of dementia residents, controlling for other resident and facility characteristics. DATA COLLECTION/EXTRACTION METHODS: Hospital-based nursing homes, those with fewer than 30% dementia residents, and missing data were excluded. PRINCIPAL FINDINGS: We found that registered nurses and certified nurse assistants HPRDs were likely to exhibit positive returns in terms of outcomes throughout most of the range of HPRD for both high and low-census dementia facilities, although, high- and low-dementia facilities differed in most outcome rates at all staffing levels. Average predicted antipsychotics and activities of daily living as functions of HPRD were worse in higher dementia facilities, independent movement, and hospitalizations did not differ significantly, and Emergency Rooms and pressure sores were worse in lower dementia facilities. Average marginal effects were not statistically different [CI included zero] between the high and low dementia facilities for any outcome. CONCLUSIONS: These findings suggest that increasing staffing will improve outcomes by similar increments in both low- and high-dementia facilities for all outcomes. However, at any given level of staffing, absolute differences in outcomes between low- and high-dementia facilities remain, suggesting that additional staffing alone will not suffice to close these gaps. Further studies are required to identify opportunities for improvement in performance for both low- and high-dementia census facilities.

BackgroundCancer patients are at risk of pulmonary embolism (PE). Catheter-based therapies (CBT) are novel reperfusion options for PE though data in patients with cancer is lacking.Study design and methodsPatients with intermediate- or high-risk PE were identified using the National Readmission Database (NRD) from 2017 to 2020. Primary outcome were in-hospital death and 90-day readmission. Secondary outcomes were in-hospital bleeding, 90-day readmission for venous thromboembolism (VTE)-related or right heart failure-related reasons and bleeding. Propensity scores were estimated using logistic regression and inverse-probability treatment weighting (IPTW) was utilized to compare outcomes between CBT and no CBT as well as CBT versus systemic thrombolysis.ResultsA total of 7785 patients were included (2511 with high-risk PE) of whom 1045 (13.4%) were managed with CBT. After IPTW, CBT was associated with lower rates of index hospitalization death (OR 0.89, 95% CI 0.83-0.96) and 90-day readmission (HR 0.75, 95% CI 0.69-0.81) but higher rates of in-hospital bleeding (OR 1.11, 95% CI 1.03-1.20) which was predominantly post-procedural bleeding. CBT was associated with lower risk of major bleeding (20.8% vs 24.8%; OR 0.80, 95% CI 0.68-0.94) compared with systemic thrombolysis.InterpretationAmong patients with cancer with intermediate or high-risk PE, CBT was associated with lower in-hospital death and 90-day readmission. CBT was also associated with decreased risk of index hospitalization major bleeding compared with systemic thrombolysis. Prospective, randomized trials with inclusion of patients with cancer are needed to confirm these findings.

ImportanceSignificant insurance status disparities have been demonstrated in head and neck cancer (HNC) outcomes. The effects of insurance status on HNC outcomes may be explained by differential access to high-quality care.ObjectiveTo evaluate the association of insurance status with the quality of the treating hospital and receipt of guideline-compliant care among patients with HNC.Design, setting, and participantsThis retrospective cohort study of data from the California Cancer Registry dataset linked with discharge records and hospital characteristics from the California Department of Health Care Access and Information included adult patients with HNC diagnosed between January 1, 2010, and December 31, 2019. Data were analyzed from May 10, 2023, to March 25, 2024.ExposuresInsurance status: commercial, Medicare, Medicaid, uninsured, other, or unknown.Main outcomes and measuresQuality of the treating hospital (tertiles), receipt of National Comprehensive Cancer Network guideline-compliant care, and overall survival.ResultsA total of 23 933 patients (mean [SD] age, 64.8 [12.3] years; 75.3% male) met the inclusion criteria. Treatment in top-tertile hospitals (hazard ratio, 0.87; 95% CI, 0.79-0.95) was associated with improved overall survival compared with treatment in bottom-tertile hospitals. Medicare (odds ratio [OR], 0.78; 95% CI, 0.73-0.84), Medicaid (OR, 0.60; 95% CI, 0.54-0.66), and uninsured (OR, 0.38; 95% CI, 0.29-0.49) status were associated with lower likelihood of treatment in high-quality hospitals compared with commercial insurance. Among patients with advanced disease, Medicaid (OR, 0.72; 95% CI, 0.62-0.83) and uninsured (OR, 0.64; 95% CI, 0.44-0.93) patients were less likely to receive dual-modality therapy. Among patients with surgically resected advanced disease, Medicaid coverage (OR, 0.73; 95% CI, 0.58-0.93) was associated with lower likelihood of receiving adjuvant radiotherapy.Conclusions and relevanceThis study found significant insurance disparities in quality of care among patients with HNC. These findings highlight the need for continued health insurance reform in the US to improve the quality of insurance coverage, in addition to expanding access to health insurance.

BACKGROUND: To enhance the utility of functional hemodynamic monitoring, the variables systolic slope (dP/dt) and dynamic arterial elastance (Eadyn) are calculated by the Hypotension Prediction Index (HPI) Acumen® Software. This study was designed to characterize the effects of phenylephrine and ephedrine on dP/dt and Eadyn. METHODS: This was a retrospective, non-randomized analysis of data collected during two clinical studies. All patients required intra-operative controlled mechanical ventilation and had an indwelling radial artery catheter connected to an Acumen IQ sensor. Raw arterial pressure waveform data was downloaded from the patient monitor and all hemodynamic measurements were calculated off-line. The anesthetic record was reviewed for bolus administrations of either phenylephrine or ephedrine. Cardiovascular variables prior to drug administration were compared to those following vasopressor administrations. The primary outcome was the difference for dP/dt and Eadyn at baseline compared with the average after the bolus administration. All data sets demonstrated non-normal distributions so statistical analysis of paired and unpaired data followed the Wilcoxon matched pairs signed-rank test or Mann-Whitney U test, respectively. RESULTS: 201 doses of phenylephrine and 100 doses of ephedrine were analyzed. All data sets are reported as median [95% CI]. Mean arterial pressure (MAP) increased from 62 [54,68] to 78 [76,80] mmHg following phenylephrine and from 59 [55,62] to 80 [77,83] mmHg following ephedrine. Stroke volume and cardiac output both increased. Stroke volume variation and pulse pressure variation decreased. Both drugs produced significant increases in dP/dt, from 571 [531, 645] to 767 [733, 811] mmHg/sec for phenylephrine and from 537 [509, 596] to 848 [779, 930] mmHg/sec for ephedrine. No significant changes in Eadyn were observed. CONCLUSION: Bolus administration of phenylephrine or ephedrine increases dP/dt but does not change Eadyn. dP/dt demonstrates potential for predicting the inotropic response to phenylephrine or ephedrine, providing guidance for the most efficacious vasopressor when treating hypotension. TRIAL REGISTRATION: Data was collected from two protocols. The first was deemed to not require written, informed consent by the Institutional Review Board (IRB). The second was IRB-approved (Effect of Diastolic Dysfunction on Dynamic Cardiac Monitors) and registered on ClinicalTrials.gov (NCT04177225).

AIM: We tested the hypothesis that visual field (VF) progression can be predicted with a deep learning model based on longitudinal pairs of optic disc photographs (ODP) acquired at earlier time points during follow-up. METHODS: 3919 eyes (2259 patients) with ≥2 ODPs at least 2 years apart, and ≥5 24-2 VF exams spanning ≥3 years of follow-up were included. Serial VF mean deviation (MD) rates of change were estimated starting at the fifth visit and subsequently by adding visits until final visit. VF progression was defined as a statistically significant negative slope at two consecutive visits and final visit. We built a twin-neural network with ResNet50-backbone. A pair of ODPs acquired up to a year before the VF progression date or the last VF in non-progressing eyes were included as input. Primary outcome measures were area under the receiver operating characteristic curve (AUC) and model accuracy. RESULTS: The average (SD) follow-up time and baseline VF MD were 8.1 (4.8) years and -3.3 (4.9) dB, respectively. VF progression was identified in 761 eyes (19%). The median (IQR) time to progression in progressing eyes was 7.3 (4.5-11.1) years. The AUC and accuracy for predicting VF progression were 0.862 (0.812-0.913) and 80.0% (73.9%-84.6%). When only fast-progressing eyes were considered (MD rate < -1.0 dB/year), AUC increased to 0.926 (0.857-0.994). CONCLUSIONS: A deep learning model can predict subsequent glaucoma progression from longitudinal ODPs with clinically relevant accuracy. This model may be implemented, after validation, for predicting glaucoma progression in the clinical setting.

STUDY OBJECTIVES: Recently, criteria have been drawn up for large muscle group movements during sleep (LMM), defined as movements lasting for 3-45 seconds in adults, which are often accompanied by changes in sleep stage, arousals, and increases in heart rate. The aim of this study was to characterize LMM in restless legs syndrome (RLS) in order to better evaluate their impact on the neurophysiology of the disorder and, therefore, the possible clinical implications. METHODS: Consecutive, drug-free patients diagnosed with RLS and controls, aged 18 years or more, were retrospectively enrolled. Leg movement activity-short-interval (SILMS), periodic (PLMS), and isolated (ISOLMS) leg movements during sleep-and LMM were detected and scored. RESULTS: In total, 100 patients and 67 controls were recruited. All movement measures were significantly higher in RLS. A significant positive correlation was found between LMM and ISOLMS index but not PLMS index in both groups. LMM index showed a significant negative correlation with total sleep time, sleep efficiency, and percentage of sleep stages N3 and R, as well as a significant positive correlation with the number of awakenings, and percentage of sleep stages N1 and N2 only in patients with RLS. No significant correlation was found between either LMM or PLMS index and RLS severity. CONCLUSIONS: Different types of movements, including SILMS, ISOLMS, and LMM, play somewhat distinct roles in sleep neurophysiology in RLS. Notably, LMM, a newly recognized category of movements, demonstrates associations with sleep architecture instability and fragmentation, arousals, and awakenings, suggesting potential clinical implications.

BACKGROUND: Endometriosis is considered as a systemic disease with the presence of proinflammatory cytokines in the circulation, which drives hypercoagulable state of endometriosis. Currently, endometriosis is classified into four stages: I (minimal), II (mild), III (moderate) and IV (severe). The aim of this study is to investigate the correlations between inflammatory markers and coagulation factors in patients diagnosed of endometriosis with stage IV. METHODS: This retrospective case-control study included 171 endometriosis patients with stage IV and 184 controls. Continuous data were expressed by mean ± standard deviation. Mann-Whitney U and χ2 tests were used to compare the medians and frequencies among the groups. Spearman analysis was conducted to determine the correlation among the measured parameters. The diagnostic values of the parameters differentiating endometriomas were tested by receiver operating characteristic (ROC) curve. RESULTS: The time of activated partial thromboplastin time (APTT) was decreased and the concentration of fibrinogen (FIB) and neutrophil-to-lymphocyte ratio (NLR) were increased in women of endometriosis with stage IV. The APTT were negatively correlated with NLR while the concentrations of FIB were positively correlated with NLR. The ROC analysis showed that the Area under the curve (AUC) of FIB was 0.766 (95% confidence interval:0.717-0.814) with sensitivity and specificity reaching 86.5 and 60.9%, respectively. The AUC of CA125 and CA199 was 0.638 (95% confidence interval: 0.578-0.697), 0.71 (95% confidence interval: 0.656-0.763) with sensitivity and specificity reaching 40.9 and 91.8%, 80.7 and 56.5% respectively. The combination of these factors showed the highest AUC of 0.895 (0.862-0.927) with sensitivity of 88.9% and specificity of 77.7%. CONCLUSION: In the present study, we found that inflammatory factors showed significant correlation with APTT or FIB in endometriosis with stage IV. Moreover, the coagulation factors combined with CA125 and CA199 were more reliable for identifying the endometriosis with stage IV.

As the microbiome field moves from descriptive and associative research to mechanistic and interventional studies, being able to account for all confounding variables in the experimental design, which includes the maternal effect1, cage effect2, facility differences3, as well as laboratory and sample handling protocols4, is critical for interpretability of results. Despite significant procedural and bioinformatic improvements, unexplained variability and lack of replicability still occur. One underexplored factor is that the microbiome is dynamic and exhibits diurnal oscillations that can change microbiome composition5-7. In this retrospective analysis of 16S amplicon sequencing studies in male mice, we show that sample collection time affects the conclusions drawn from microbiome studies and its effect size is larger than those of a daily experimental intervention or dietary changes. The timing of divergence of the microbiome composition between experimental and control groups is unique to each experiment. Sample collection times as short as only 4 hours apart can lead to vastly different conclusions. Lack of consistency in the time of sample collection may explain poor cross-study replicability in microbiome research. The impact of diurnal rhythms on the outcomes and study design of other fields is unknown but likely significant.

BACKGROUND: Primary Health Care (PHC) is essential for effective, efficient, and more equitable health systems for all people, including those living with HIV/AIDS. This study evaluated the impact of the exposure to one of the largest community-based PHC programs in the world, the Brazilian Family Health Strategy (FHS), on AIDS incidence and mortality. METHODS AND FINDINGS: A retrospective cohort study carried out in Brazil from January 1, 2007 to December 31, 2015. We conducted an impact evaluation using a cohort of 3,435,068 ≥13 years low-income individuals who were members of the 100 Million Brazilians Cohort, linked to AIDS diagnoses and deaths registries. We evaluated the impact of FHS on AIDS incidence and mortality and compared outcomes between residents of municipalities with low or no FHS coverage (unexposed) with those in municipalities with 100% FHS coverage (exposed). We used multivariable Poisson regressions adjusted for all relevant municipal and individual-level demographic, socioeconomic, and contextual variables, and weighted with inverse probability of treatment weighting (IPTW). We also estimated the FHS impact by sex and age and performed a wide range of sensitivity and triangulation analyses; 100% FHS coverage was associated with lower AIDS incidence (rate ratio [RR]: 0.76, 95% CI: 0.68 to 0.84) and mortality (RR: 0.68, 95%CI: 0.56 to 0.82). FHS impact was similar between men and women, but was larger in people aged ≥35 years old both for incidence (RR: 0.62, 95% CI: 0.53 to 0.72) and mortality (RR: 0.56, 95% CI: 0.43 to 0.72). The absence of important confounding variables (e.g., sexual behavior) is a key limitation of this study. CONCLUSIONS: AIDS should be an avoidable outcome for most people living with HIV today and our study shows that FHS coverage could significantly reduce AIDS incidence and mortality among low-income populations in Brazil. Universal access to comprehensive healthcare through community-based PHC programs should be promoted to achieve the Sustainable Development Goals of ending AIDS by 2030.

Purpose To develop, externally test, and evaluate clinical acceptability of a deep learning pediatric brain tumor segmentation model using stepwise transfer learning. Materials and Methods In this retrospective study, the authors leveraged two T2-weighted MRI datasets (May 2001 through December 2015) from a national brain tumor consortium (n = 184; median age, 7 years [range, 1-23 years]; 94 male patients) and a pediatric cancer center (n = 100; median age, 8 years [range, 1-19 years]; 47 male patients) to develop and evaluate deep learning neural networks for pediatric low-grade glioma segmentation using a stepwise transfer learning approach to maximize performance in a limited data scenario. The best model was externally tested on an independent test set and subjected to randomized blinded evaluation by three clinicians, wherein they assessed clinical acceptability of expert- and artificial intelligence (AI)-generated segmentations via 10-point Likert scales and Turing tests. Results The best AI model used in-domain stepwise transfer learning (median Dice score coefficient, 0.88 [IQR, 0.72-0.91] vs 0.812 [IQR, 0.56-0.89] for baseline model; P = .049). With external testing, the AI model yielded excellent accuracy using reference standards from three clinical experts (median Dice similarity coefficients: expert 1, 0.83 [IQR, 0.75-0.90]; expert 2, 0.81 [IQR, 0.70-0.89]; expert 3, 0.81 [IQR, 0.68-0.88]; mean accuracy, 0.82). For clinical benchmarking (n = 100 scans), experts rated AI-based segmentations higher on average compared with other experts (median Likert score, 9 [IQR, 7-9] vs 7 [IQR 7-9]) and rated more AI segmentations as clinically acceptable (80.2% vs 65.4%). Experts correctly predicted the origin of AI segmentations in an average of 26.0% of cases. Conclusion Stepwise transfer learning enabled expert-level automated pediatric brain tumor autosegmentation and volumetric measurement with a high level of clinical acceptability. Keywords: Stepwise Transfer Learning, Pediatric Brain Tumors, MRI Segmentation, Deep Learning Supplemental material is available for this article. © RSNA, 2024.

ObjectiveDespite an increase in twin pregnancies in recent decades, the Institute of Medicine twin weight gain recommendations remain provisional and provide no guidance for the pattern or timing of weight change. We sought to characterize gestational weight change trajectory patterns and examine associations with birth outcomes in a cohort of twin pregnancies.Study designPrenatal and delivery records were examined for 320 twin pregnancies from a maternal-fetal medicine practice in Austin, TX 2011-2019. Prenatal weights for those with >1 measured weight in the first trimester and ≥3 prenatal weights were included in analyses. Trajectories were estimated to 32 weeks (mean delivery: 33.7 ± 3.3 weeks) using flexible latent class mixed models with low-rank thin-plate splines. Associations between trajectory classes and infant outcomes were analyzed using multivariable Poisson or linear regression.ResultsWeight change from prepregnancy to delivery was 15.4 ± 6.3 kg for people with an underweight body mass index, 15.4 ± 5.8 kg for healthy weight, 14.7 ± 6.9 kg for overweight, and 12.5 ± 6.4 kg for obesity. Three trajectory classes were identified: low (Class 1), moderate (Class 2), or high gain (Class 3). Class 1 (24.7%) maintained weight for 15 weeks and then gained an estimated 6.6 kg at 32 weeks. Class 2 (60.9%) exhibited steady gain with 13.5 kg predicted total gain, and Class 3 (14.4%) showed rapid gain across pregnancy with 21.3 kg predicted gain. Compared to Class 1, Class 3 was associated with higher birth weight z-score (β = 0.63, 95% confidence interval [CI]: 0.31,0.96), increased risk for large for gestational age (IRR = 5.60, 95% CI: 1.59, 19.67), and birth

BACKGROUND: Patients with limited English proficiency (LEP) may have worse health outcomes and differences in processes of care. Language status may particularly affect situations that depend on communication, such as symptom management or end-of-life (EOL) care. OBJECTIVE: The objective of this study was to assess whether opioid prescribing and administration differs by English proficiency (EP) status among hospitalized patients receiving EOL care. METHODS: This single-center retrospective study identified all adult patients receiving comfort care on the general medicine service from January 2013 to September 2021. We assessed for differences in the quantity of opioids administered (measured by oral morphine equivalents [OME]) by patient LEP status using multivariable linear regression, controlling for other patient and medical factors. RESULTS: We identified 2652 patients receiving comfort care at our institution during the time period, of whom 1813 (68%) died during the hospitalization. There were no significant differences by LEP status in terms of mean OME per day (LEP received 30.8 fewer OME compared to EP, p = .91) or in the final 24 h before discharge (LEP received 61.7 more OME compared to EP, p = .80). CONCLUSION: LEP was not associated with differences in the amount of opioids received for patients whose EOL management involved standardized order sets for symptom management at our hospital.

BACKGROUND: Neurotrophic tyrosine receptor kinase (NTRK) gene fusions are rare oncogenic drivers prevalent in 0.3% of solid tumors. They are most common in salivary gland cancer (2.6%), thyroid cancer (1.6%), and soft-tissue sarcoma (1.5%). Currently, there are 2 US Food and Drug Administration-approved targeted therapies for NTRK gene fusions: larotrectinib, approved in 2018, and entrectinib, approved in 2019. To date, the real-world uptake of tyrosine receptor kinase inhibitor (TRKi) use for NTRK-positive solid tumors in academic cancer centers remains largely unknown. OBJECTIVE: To describe the demographics, clinical and genomic characteristics, and testing and treatment patterns of patients with NTRK-positive solid tumors treated at US academic cancer centers. METHODS: This was a retrospective chart review study conducted in academic cancer centers in the United States. All patients diagnosed with an NTRK fusion-positive (NTRK1, NTRK2, NTRK3) solid tumor (any stage) and who received cancer treatment at participating sites between January 1, 2012, and July 1, 2023, were included in this study. Patient demographics, clinical characteristics, genomic characteristics, NTRK testing data, and treatment patterns were collected from electronic medical records and analyzed using descriptive statistics as appropriate. RESULTS: In total, 6 centers contributed data for 55 patients with NTRK-positive tumors. The mean age was 49.3 (SD = 20.5) years, 51% patients were female, and the majority were White (78%). The median duration of time from cancer diagnosis to NTRK testing was 85 days (IQR = 44-978). At the time of NTRK testing, 64% of patients had stage IV disease, compared with 33% at cancer diagnosis. Prevalent cancer types in the overall cohort included head and neck (15%), thyroid (15%), brain (13%), lung (13%), and colorectal (11%). NTRK1 fusions were most common (45%), followed by NTRK3 (40%) and NTRK2 (15%). Across all lines of therapy, 51% of patients (n = 28) received a TRKi. Among TRKi-treated patients, 71% had stage IV disease at TRKi initiation. The median time from positive NTRK test to initiation of TRKi was 48 days (IQR = 9-207). TRKis were commonly given as first-line (30%) or second-line (48%) therapies. Median duration of therapy was 610 (IQR = 182-764) days for TRKi use and 207.5 (IQR = 42-539) days for all other first-line therapies. CONCLUSIONS: This study reports on contemporary real-world NTRK testing patterns and use of TRKis in solid tumors, including time between NTRK testing and initiation of TRKi therapy and duration of TRKi therapy.

OBJECTIVES: To describe the utilization of early ketamine use among patients mechanically ventilated for COVID-19, and examine associations with in-hospital mortality and other clinical outcomes. DESIGN: Retrospective cohort study. SETTING: Six hundred ten hospitals contributing data to the Premier Healthcare Database between April 2020 and June 2021. PATIENTS: Adults with COVID-19 and greater than or equal to 2 consecutive days of mechanical ventilation within 5 days of hospitalization. INTERVENTION: The exposures were early ketamine use initiated within 2 days of intubation and continued for greater than 1 day. MEASUREMENTS: Primary was hospital mortality. Secondary outcomes included length of stay (LOS) in the hospital and ICUs, ventilator days, vasopressor days, renal replacement therapy (RRT), and total hospital cost. The propensity score matching analysis was used to adjust for confounders. MAIN RESULTS: Among 42,954 patients, 1,423 (3.3%) were exposed to early ketamine use. After propensity score matching including 1,390 patients in each group, recipients of ketamine infusions were associated with higher hospital mortality (52.5% vs. 45.9%, risk ratio: 1.14, [1.06-1.23]), longer median ICU stay (13 vs. 12 d, mean ratio [MR]: 1.15 [1.08-1.23]), and longer ventilator days (12 vs. 11 d, MR: 1.19 [1.12-1.27]). There were no associations for hospital LOS (17 [10-27] vs. 17 [9-28], MR: 1.05 [0.99-1.12]), vasopressor days (4 vs. 4, MR: 1.04 [0.95-1.14]), and RRT (22.9% vs. 21.7%, RR: 1.05 [0.92-1.21]). Total hospital cost was higher (median $72,481 vs. $65,584, MR: 1.11 [1.05-1.19]). CONCLUSIONS: In a diverse sample of U.S. hospitals, about one in 30 patients mechanically ventilated with COVID-19 received ketamine infusions. Early ketamine may have an association with higher hospital mortality, increased total cost, ICU stay, and ventilator days, but no associations for hospital LOS, vasopressor days, and RRT. However, confounding by the severity of illness might occur due to higher extracorporeal membrane oxygenation and RRT use in the ketamine group. Further randomized trials are needed to better understand the role of ketamine infusions in the management of critically ill patients.

OBJECTIVE: Despite limited safety and efficacy data, inhaled corticosteroids (ICS) are prescribed to premature infants in the neonatal intensive care unit (NICU). We examined contemporary use and risk factors for ICS use in the NICU. STUDY DESIGN: Infants

BACKGROUND: Surgeons have come under increased scrutiny for postoperative pain management, particularly for opioid prescribing. To decrease opioid use but still provide pain control, nonopioid medications such as muscle relaxants are being used, which can be harmful in older adults. However, the prevalence of muscle relaxant prescribing, trends in use over time, and risk of prolonged use are unknown. STUDY DESIGN: Using a 20% representative Medicare sample, we conducted a retrospective analysis of muscle relaxant prescribing to patients ≥ 65 years of age. We merged patient data from Medicare Carrier, MedPAR, and Outpatient Files with Medicare Part D for the years 2013-2018. A total of 14 surgical procedures were included to represent a wide range of anatomic regions and specialties. RESULTS: The study cohort included 543,929 patients. Of the cohort, 8111 (1.5%) received a new muscle relaxant prescription at discharge. Spine procedures accounted for 12% of all procedures but 56% of postoperative prescribing. Overall, the rate of prescribing increased over the time period (1.4-2.0%, p < 0.001), with increases in prescribing primarily in the spine (7-9.6%, p < 0.0001) and orthopedic procedure groups (0.9-1.4%, p < 0.0001). Of patients discharged with a new muscle relaxant prescription, 10.7% had prolonged use. CONCLUSIONS: The use of muscle relaxants in the postoperative period for older adults is low, but increasing over time, especially in ortho and spine procedures. While pain control after surgery is crucial, surgeons should carefully consider the risks of muscle relaxant use, especially for older adults who are at higher risk for medication-related problems.

BACKGROUND: Patients with telomere biology disorders (TBD) develop hepatic disease, including hepatitis, cirrhosis, and hepatopulmonary syndrome. No specific treatment exists for TBD-related liver disease, and the role of liver transplantation (LT) remains controversial. Our study objectives were to describe the clinical characteristics, management, and outcomes in patients with TBD-related liver disease, and their LT outcomes. METHODS: Data from 83 patients with TBD-associated liver disease were obtained from 17 participating centers in the Clinical Care Consortium of Telomere-Associated Ailments and by self-report for our retrospective, multicenter, international cohort study. RESULTS: Group A (Advanced) included 40 patients with advanced liver disease. Of these, 20 underwent LT (Group AT). Group M (Mild) included 43 patients not warranting LT evaluation, none of whom were felt to be medically unfit for liver transplantation. Supplemental oxygen requirement, pulmonary arteriovenous malformation, hepatopulmonary syndrome, and higher bilirubin and international normalized ratio values were associated with Group A. Other demographics, clinical manifestations, and laboratory findings were similar between groups. Six group A patients were declined for LT; 3 died on the waitlist. Median follow-up post-LT was 2.9 years (range 0.6-13.2 y). One-year survival post-LT was 73%. Median survival post-LT has not been reached. Group AT patients had improved survival by age compared to all nontransplant patients (log-rank test p = 0.02). Of 14 patients with pretransplant hypoxemia, 8 (57%) had improved oxygenation after transplant. CONCLUSIONS: LT recipients with TBD do not exhibit excessive posttransplant mortality, and LT improved respiratory status in 57%. A TBD diagnosis should not exclude LT consideration.

BackgroundSurgical treatment of recurrent rectal prolapse is associated with unique technical challenges, partially determined by the surgical approach used for the index operation. Success rates are variable, and data to determine the best approach in patients with recurring prolapse are lacking.ObjectiveThe study aimed to assess current surgical approaches to patients with prior rectal prolapse repairs and to compare short-term outcomes of de novo and redo procedures, including recurrence of rectal prolapse.DesignRetrospective analysis of a prospective database.SettingsThe Multicenter Pelvic Floor Disorders Consortium Prospective Quality Improvement database. De-identified surgeons at more than 25 sites (81% high volume) self-reported patient demographics, prior repairs, symptoms of incontinence and obstructed defecation, and operative details, including history of concomitant repairs and prior prolapse repairs.PatientsPatients who were offered surgery for full thickness rectal prolapse.InterventionsIncidence and type of repair used for prior rectal prolapse surgery were recorded. Primary and secondary outcomes of index and redo operations were calculated. Patients undergoing rectal prolapse re-repair (redo) were compared with patients undergoing first (de novo) rectal prolapse repair. The incidence of rectal prolapse recurrence in de novo and redo operations was quantified.OutcomesThe primary outcome of rectal prolapse recurrence in de novo and redo settings.ResultsEighty-nine (19.3%) of 461 patients underwent redo rectal prolapse repair. On short-term follow-up, redo patients had prolapse recurrence rates similar to those undergoing de novo repair. However, patients undergoing redo procedures rarely had the same operation as their index procedure.LimitationsSelf-reported, de-identified data.ConclusionOur results suggest that recurrent rectal prolapse surgery is feasible and can offer adequate rates of rectal prolapse durability in the short term but may argue for a change in surgical approach for redo procedures when clinically feasible. See Video Abstract .Los enfoques duraderos para la reparacin del prolapso rectal recurrente pueden requerir evitar el procedimiento ndiceANTECEDENTES:El tratamiento quirúrgico del prolapso rectal recurrente se asocia con desafíos técnicos únicos, determinados en parte por el abordaje quirúrgico utilizado para la operación inicial. Las tasas de éxito son variables y faltan datos para determinar el mejor abordaje en pacientes con prolapso recurrente.OBJETIVO:Evaluar los enfoques quirúrgicos actuales para pacientes con reparaciones previas de prolapso rectal y comparar los resultados a corto plazo de los procedimientos de novo y rehacer, incluida la recurrencia del prolapso rectal.DISEÑO:Análisis retrospectivo de una base de datos prospectiva.AJUSTE:Base de datos de mejora prospectiva de la calidad del Consorcio multicéntrico de trastornos del suelo pélvico. Cirujanos no identificados en más de 25 sitios (81% de alto volumen) informaron datos demográficos de los pacientes, reparaciones previas, síntomas de incontinencia y defecación obstruida y detalles operativos, incluido el historial de reparaciones concomitantes y reparaciones previas de prolapso.INTERVENCIONES:Se registro la incidencia y el tipo de reparación utilizada para la cirugía de prolapso rectal previa. Se calcularon los resultados primarios y secundarios de las operaciones de índice y reoperacion. Se compararon los pacientes sometidos a una nueva reparación (reoperacion) de prolapso rectal con pacientes sometidos a una primera reparación (de novo) de prolapso rectal. Se cuantificó la incidencia de recurrencia del prolapso rectal en operaciones de novo y rehacer.RESULTADOS:El resultado primario de recurrencia del prolapso rectal en entornos de novo y redo. Ochenta y nueve (19,3%) de 461 pacientes se sometieron a una nueva reparación del prolapso rectal. En el seguimiento a corto plazo, los pacientes reoperados tuvieron tasas de recurrencia de prolapso similares a los de los sometidos a reparación de novo. Sin embargo, los pacientes sometidos a procedimientos de rehacer rara vez tuvieron la misma operación que su procedimiento índice.LIMITACIONES:Datos no identificados y autoinformados.CONCLUSIONES/DISCUSIÓN:Nuestros resultados sugieren que la cirugía de prolapso rectal recurrente es factible y puede ofrecer tasas adecuadas de durabilidad del prolapso rectal en el corto plazo, pero puede abogar por un cambio en el enfoque quirúrgico para rehacer los procedimientos cuando sea clínicamente factible. (Traducción-Dr. Mauricio Santamaria ).

BACKGROUND: Fibrosis-4 (FIB4) is a recommended noninvasive test to assess hepatic fibrosis among patients with metabolic dysfunction-associated steatotic liver disease (MASLD). Here, we used FIB4 trajectory over time (ie, slope of FIB4) as a surrogate marker of liver fibrosis progression and examined if FIB4 slope is associated with clinical and genetic factors among individuals with clinically defined MASLD within the Million Veteran Program Cohort. METHODS: In this retrospective cohort study, FIB4 slopes were estimated through linear regression for participants with clinically defined MASLD and FIB4

PURPOSE: Defining prostate cancer contours is a complex task, undermining the efficacy of interventions such as focal therapy. A multireader multicase study compared physicians' performance using artificial intelligence (AI) vs standard-of-care methods for tumor delineation. MATERIALS AND METHODS: Cases were interpreted by 7 urologists and 3 radiologists from 5 institutions with 2 to 23 years of experience. Each reader evaluated 50 prostatectomy cases retrospectively eligible for focal therapy. Each case included a T2-weighted MRI, contours of the prostate and region(s) of interest suspicious for cancer, and a biopsy report. First, readers defined cancer contours cognitively, manually delineating tumor boundaries to encapsulate all clinically significant disease. Then, after ≥ 4 weeks, readers contoured the same cases using AI software. Using tumor boundaries on whole-mount histopathology slides as ground truth, AI-assisted, cognitively-defined, and hemigland cancer contours were evaluated. Primary outcome measures were the accuracy and negative margin rate of cancer contours. All statistical analyses were performed using generalized estimating equations. RESULTS: The balanced accuracy (mean of voxel-wise sensitivity and specificity) of AI-assisted cancer contours (84.7%) was superior to cognitively-defined (67.2%) and hemigland contours (75.9%; P < .0001). Cognitively-defined cancer contours systematically underestimated cancer extent, with a negative margin rate of 1.6% compared to 72.8% for AI-assisted cancer contours (P < .0001). CONCLUSIONS: AI-assisted cancer contours reduce underestimation of prostate cancer extent, significantly improving contouring accuracy and negative margin rate achieved by physicians. This technology can potentially improve outcomes, as accurate contouring informs patient management strategy and underpins the oncologic efficacy of treatment.

BACKGROUND: Serum AFP-L3%, AFP, and DCP are useful biomarkers for HCC detection, but their utility in assessing treatment response remains unknown. We aim to evaluate the accuracy of a biomarker model in the detection of posttreatment viable tumors. METHODS: For model derivation, recipients with HCC undergoing liver transplant from 2018 to 2022 who had biomarkers collected within 3 months before transplant were included. We developed a generalized linear model for detecting posttreatment viable tumors with the 3 biomarkers as covariates, which we termed the LAD Score. An independent cohort of 117 patients with HCC was used for external validation. RESULTS: Among 205 recipients of transplant, 70.2% had evidence of viable tumor on explant. The median LAD score was higher among patients with viable versus nonviable tumors (1.06 vs. 0.465, p < 0.001). The LAD score had a sensitivity of 55.6% and a specificity of 85.1% at the cutoff of 0.927, which was more accurate than imaging for detecting posttreatment viable tumors (AUROC 0.736 vs. 0.643, respectively; p = 0.045). The superior performance of the LAD score over imaging is primarily driven by its greater accuracy in detecting tumors

Context: Among many unanticipated changes, access to rehabilitation was disrupted during the onset of the COVID-19 pandemic. It is unclear how the timing of late-stage rehabilitation following anterior cruciate ligament with surgical reconstruction (ACLR) during the initial months of the pandemic affected outcomes. The purpose of this study was to compare physical performance outcome measures in patients following ACLR prior to and following COVID-19-related restrictions. Design: Retrospective cohort study. Methods: Data from patients who underwent return-to-sport testing following ACLR were analyzed based on date. December 2018 through March of 2020 (n = 66) was defined as the baseline period, and June through October 2020 (n = 27) was defined as the surveillance period. Outcome measures included single leg hop, triple hop, single leg vertical jump, and the lower-extremity functional test (LEFT). Linear mixed models were used to compare outcome measures before and after the onset of pandemic-related restrictions, clustered by sex and sport. A 1-way analysis of variance was performed to analyze the association between the number of virtual rehabilitation visits and outcome measures for subjects in the surveillance period. Results: Subjects in the surveillance period performed significantly worse in the LEFT (+7.88 s; 95% confidence interval, 1.11 to 14.66; P =.02) and single leg vertical jump on the unaffected side (−4.32 cm; 95% confidence interval, −7.44 to −1.19, P <.01), and performed better with single leg vertical jump symmetry (+6.3%; 95% confidence interval, 1.0% to 11.5%; P =.02). There were no other statistically significant differences. There was no significant association between having virtual rehabilitation visits and any of the performance outcomes. Conclusions: There was a decline in physical performance outcome measures in patients following ACLR who did not attend regular in-person physical therapy sessions in the late-stage rehabilitation due to COVID-19-related restrictions. Other factors during this unique time period, such as access to training facilities or psychosocial stressors, may have also influenced outcomes. [ABSTRACT FROM AUTHOR]

Objectives: Sedation is commonly utilized for individuals otherwise unable to receive dental treatment, such as those with disabilities, medically complex conditions, and dentophobics. The aim was to characterize the profiles of patients receiving various types of sedation and assess the corresponding success rates. Method and materials: This was a 5-year records-based retrospective study. Data regarding the indication for sedation, medical history, sedation type, and treatments performed were recorded. Results: In total, 103 patients underwent 389 treatment sessions under sedation; 42.7% of the patients were disabled. The most commonly administered sedation was moderate sedation, (49.4%), followed by deep (36.8%) and inhaled sedation (13.9%). Successful treatment results were achieved in 96.1% of sessions, with no adverse effects noted during recovery. The high success rates were independent of patient age, sex, and sedation type. There was a positive association between the indication for sedation and the type of sedation. The medically complex patients and the dentophobic patients received mainly moderate sedation (85.3% and 58.2%, respectively), whereas the disabled patients received deep sedation (51.2%). In total, 94% of patients were returning (revisiting) patients. A statistically significant association was found between the type of sedation administered and the success rate during the first and last sessions (P< .001). The success rate at the first session may be predictive of the success in subsequent sessions. Conclusion: A significant positive correlation was found between patient characteristics and the chosen sedation type leading to a high success rate across the various sedation modalities. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate bone preservation and esthetic recovery between the socket-shield technique (SST) with different labial bone plate thicknesses and the conventional immediate implant technique (CIIT). Materials and Methods: Patients who underwent immediate implant placement in the anterior region were divided into three groups: the SST with a thickwall phenotype (> 1 mm; SSTA group), the SST with a thin-wall phenotype (< 1 mm; SSTB group), and the CIIT with a thickwall phenotype (> 1 mm; CIIT group). Radiologic images and clinical photos were collected before surgery, immediately postoperatively, and 6 months postoperatively. The labial bone width, labial bone width change (BWC), labial bone volume change (BVC), pink esthetic score (PES), and complication rate were evaluated among the three groups. Statistical analysis was performed using SPSS software. Results: A total of 60 patients (n = 20/group) were enrolled in this 6-month retrospective study. The BWC in the SSTA group (0.22 to 0.30 mm) and the SSTB group (0.18 to 0.33 mm) was less than that in the CIIT group (0.61 to 0.80 mm; P < .004). The SSTA group and the SSTB group had a lower BVC (24.08 vs 21.14 vs 54.81, respectively; P = .004) and greater PES (11.75 vs 11.65 vs 10.65, respectively; P = .009) than the CIIT group. No complications occurred among these patients. Conclusions: With the limitations of this study, it can be concluded that the SST is a reliable method for preserving bone and achieving satisfactory esthetic outcomes. The labial bone plate phenotype associated with the SST has minimal impact on both clinical and radiologic outcomes. [ABSTRACT FROM AUTHOR]

Purpose: To retrospectively determine the cumulative survival rate (CSR) and marginal bone level change (ΔMBL) around novel hybrid design tissue-level (TL) dental implants that support multiple-screw-retained restorations. Materials and Methods: Implant CSRs were analyzed at the implant and patient level using Kaplan-Meier estimates. ΔMBL was measured by comparing the periapical loading and follow-up visit radiographs using an improved standardized digital methodology based on image gray levels. ΔMBL outcomes were subject to linear mixed regression to identify potential risk factors. Results: A total of 301 TL implants in 69 patients with an average age of 62.6 ± 11.7 years (range: 36 to 87 years) at the time of implant placement were considered for the analysis. All 301 implants were successfully restored and loaded. The 54-month CSRs at the implant and patient levels were 98.9% (95% CI: 96.7 to 99.6) and 95.3% (95% CI: 86.1 to 98.5), respectively. ΔMBL after a mean follow-up of 22 ± 10.7 months after loading was 0.00 ± 0.57 mm. None of the implant sites showed marginal bone loss exceeding 1.5 mm. Multivariate regression analysis revealed a significant association between ΔMBL and the loading protocol (P = .027) but not between ΔMBL and age or transgingival height. Conclusions: The high CSRs and stable peri-implant marginal bone levels support the use of recent TL implants, which have a hybrid design inherited from the bone-level implant-abutment connection, as a suitable treatment option for restoring partially or fully edentulous patients with a good mid-term prognosis. These results should be complemented by further prospective studies in a real-world multicenter private practice setup that represents the daily realities of implant treatment. [ABSTRACT FROM AUTHOR]

This retrospective study evaluated the clinical outcomes of surgical crown reattachment in the treatment of complicated crown-root fractures in permanent teeth in 35 patients. Treatments were defined as follows: surgical crown reattachment combined with internal fixation with a fiber-reinforced core post, ostectomy, and reattachment of the original crown fragment. Patients were examined to record the periodontal pocket depth (PD), marginal bone loss, tooth migration, and coronal fragment looseness or loss. In most cases, the fracture lines on the palatal aspect were located below the alveolar crest. About 20% to 30% of teeth had periodontal pockets ≥ 3 mm present at least 1 year after surgery. Significant PD differences were observed between the traumatized teeth and adjacent untraumatized teeth at 6 months. The available evidence suggests that surgical crown reattachment is a feasible and effective technique for managing complicated crown-root fractures in permanent teeth. [ABSTRACT FROM AUTHOR]

Sinus membrane thickening is a common maxillary sinus disease. However, a consensus has not been reached on the effect of sinus membrane thickness on the transcrestal sinus floor elevation. This retrospective study evaluated the perforation and bone formation at transcrestal sinus floor elevation sites with different sinus membrane thicknesses. A total of 117 sites in 87 patients treated with transcrestal sinus floor elevation were included in this study. The surgical sites were divided into four groups according to the baseline sinus membrane thickness: Group A (0 to 1 mm), Group B (1 to 2 mm), Group C (2 to 4 mm), and Group D (> 4 mm). CBCT scans were taken before surgery, immediately after surgery, and 6 months after surgery. The mean baseline sinus membrane thickness was 2.16 ± 2.54 mm, and the mean residual alveolar bone height was 6.58 ± 1.85 mm. The mean endosinus new bone height was 3.76 ± 1.95 mm. The perforation rate and endosinus new bone height showed no significant difference among the groups (P > .05). The incidence rates of membrane thickening and perforation were significantly higher in smoking patients (P < .05). Membrane thickening without ostium obstruction may have little impact on transcrestal sinus floor elevation surgery in regards to perforation rate and bone formation. In addition, smoking may be a risk factor for membrane thickening, and the sinus membrane is more likely to perforate during transcrestal surgery when the patient has a history of smoking. [ABSTRACT FROM AUTHOR]

Objective: The purpose of the study was to determine how the maxillary non-impacted third molars impact the distal region of alveolar bone of adjacent second molars. Method and materials: The periodontal condition of maxillary second molars for which the neighboring third molars were missing (NM3- group) and those with intact non-impacted third molars (NM3+ group) was analyzed in a retrospective study. Using CBCT, the patients were categorized based on the presence or absence of periodontitis, and the alveolar bone resorption parameters in the distal area of the second molars were measured. Results: A total of 135 patients with 200 maxillary second molars were enrolled in this retrospective study. Compared to the NM3- group, the second molars of the NM3+ group exhibited greater odds of increasing alveolar bone resorption in the distal region (health, OR = 3.60; periodontitis, OR = 7.68), regardless of the presence or absence of periodontitis. In healthy patients, factors such as female sex (OR = 1.48) and age above 25 years old (OR = 2.22) were linked to an elevated risk of alveolar bone resorption in the distal region of the second molars. In patients with periodontitis, male sex (OR = 3.63) and age above 45 years old (OR = 3.97) served as risk factors. Conclusions: Advanced age, sex, and the presence of non-impacted third molars are risk factors associated with alveolar bone resorption in individuals with adjacent second molars. In addition, the detrimental effects of non-impacted third molars in the population with periodontitis may be exacerbated. From a periodontal perspective, this serves as supportive evidence for the proactive removal of non-impacted third molars. [ABSTRACT FROM AUTHOR]