Search

BACKGROUND: Household contact investigation is an important strategy to identify individuals with tuberculosis (TB) exposure, infection, and disease, including those who may benefit from tuberculosis preventive therapy (TPT). Data in children exposed to rifampin-resistant TB are limited. METHODS: In preparation for and to inform the feasibility of an interventional trial, household contacts (HHC) of adults with pulmonary rifampin-resistant TB from high TB-burden countries were evaluated in a cross-sectional study. Using interferon gamma release assay (IGRA) and study-specific and 2015 international consensus definitions of intrathoracic TB in children, we evaluated the prevalence and predictors of TB infection and disease in child (

Postoperative patient satisfaction after anterior cruciate ligament reconstruction (ACL-R) is influenced mainly by the degree of pain, the need for reoperation, and functional performance in daily activities and sports. Graft choice has shown to have an influence on postoperative outcomes after ACL-R. While patient reported outcomes measurements do not differ between graft options, evidence shows that normal knee kinematics is not fully restored after ACL-R with an increase in postoperative anterior tibial translation (ATT). Postoperative graft rupture rates seem to favor bone-patella-tendon-bone (BPTB) and quadriceps tendon (QT) autografts over HT or allografts. While return to sports rates seem comparable between different graft types, postoperative extensor strength is reduced in patients with BPTB and QT whereas flexion strength is weakened in patients with HT. Postoperative donor site morbidity is highest in BPTB but comparable between HT and QT. With all graft options having advantages and drawbacks, graft choice must be individualized and chosen in accordance with the patient.

PDF file, 5465KB, Quantitation tables for proteins identified and quantified.

PDF file, 3.66MB, Proteomic data table. Tabular list of proteomic data from the 2 hr and 16 hour gefitinib treated experiments. Whole cell lysate (WCL), cell-surface (SUR), and SPEG/GC.

Affinity Purification of EGFR, JUN, JNK, and FOS

PDF file, 47KB, Protein Identification for Solid Phase Extraction of Glycoproteins (SPEG)with 16 hours of gefitinib treatment.

PDF file, 131KB, Basal levels protein biomarkers. Basal levels of EpCAM, ELAVL1, and CBFB demonstrate a correlation to gefitinib sensitivity. Non-treated NSCLC lysates, synchronized by serum starvation for 16 hours, were generated and assayed for basal protein levels by Western blot.

PDF file, 83KB.

Supplemental text, figures, and data

PDF file, 321KB, Protein levels changes associated with EGFR targeted and non-EGFR targeted drugs.

PDF file, 299KB, Protein level changes associated with gefitinib treatment in NSCLC tissue.

Clinical oncology is hampered by lack of tools to accurately assess a patient's response to pathway-targeted therapies. Serum and tumor cell surface proteins whose abundance, or change in abundance in response to therapy, differentiates patients responding to a therapy from patients not responding to a therapy could be usefully incorporated into tools for monitoring response. Here, we posit and then verify that proteomic discovery in in vitro tissue culture models can identify proteins with concordant in vivo behavior and further, can be a valuable approach for identifying tumor-derived serum proteins. In this study, we use stable isotope labeling of amino acids in culture (SILAC) with proteomic technologies to quantitatively analyze the gefitinib-related protein changes in a model system for sensitivity to EGF receptor (EGFR)-targeted tyrosine kinase inhibitors. We identified 3,707 intracellular proteins, 1,276 cell surface proteins, and 879 shed proteins. More than 75% of the proteins identified had quantitative information, and a subset consisting of 400 proteins showed a statistically significant change in abundance following gefitinib treatment. We validated the change in expression profile in vitro and screened our panel of response markers in an in vivo isogenic resistant model and showed that these were markers of gefitinib response and not simply markers of phospho-EGFR downregulation. In doing so, we also were able to identify which proteins might be useful as markers for monitoring response and which proteins might be useful as markers for a priori prediction of response. Mol Cancer Ther; 11(5); 1071–81. ©2012 AACR.

Graft selection in anterior cruciate ligament (ACL) reconstruction is critical, as it remains one of the most easily adjustable factors affecting graft rupture and reoperation rates. Commonly used autografts, including hamstring tendon, quadriceps tendon and bone-patellar-tendon-bone, are reported to be biomechanically equivalent or superior compared to the native ACL. Despite this, such grafts are unable to perfectly replicate the complex anatomical and histological characteristics of the native ACL. While there remains inconclusive evidence as to the superiority of one autograft in terms of graft incorporation and maturity, allografts appear to demonstrate slower incorporation and maturity compared to autografts. Graft fixation also affects graft properties and subsequent outcomes, with each technique having unique advantages and disadvantages that should be carefully considered during graft selection.

Aim To examine impact of adverse childhood experiences (ACE) on rates and development of multimorbidity across three decades in adulthood. Methods Sample: Participants from the 1946 National Survey of Health and Development, who attended the age 36 assessment in 1982 and follow-up assessments (ages 43, 53, 63, 69; N = 3,264, 51% males). Prospectively collected data on nine ACEs was grouped into (i) psychosocial, (ii) parental health and (iii) childhood health. For each group, we calculated cumulative ACE scores, categorised into 0, 1 and ≥2 ACEs. Multimorbidity was estimated as the total score of 18 health disorders. Serial cross-sectional linear regression was used to estimate associations between grouped ACEs and multimorbidity during follow-up. Longitudinal analysis of ACE-associated changes in multimorbidity trajectories across follow-up was estimated using linear mixed-effects modelling for ACE groups (adjusted for sex and childhood socioeconomic circumstances). Findings Accumulation of psychosocial and childhood health ACEs were associated with progressively higher multimorbidity scores throughout follow-up. For example, those with ≥2 psychosocial ACEs experienced 0.20(95% CI 0.07, 0.34) more disorders at age 36 than those with none, rising to 0.61(0.18, 1.04) disorders at age 69. All three grouped ACEs were associated with greater rates of accumulation and higher multimorbidity trajectories across adulthood. For example, individuals with ≥2 psychosocial ACEs developed 0.13(−0.09, 0.34) more disorders between ages 36 and 43, 0.29(0.06, 0.52) disorders between ages 53 and 63, and 0.30(0.09, 0.52) disorders between ages 63 and 69 compared with no psychosocial ACEs. Interpretations ACEs are associated with widening inequalities in multimorbidity development in adulthood and early old age. Public health policies should aim to reduce these disparities through individual and population-level interventions.

PURPOSE OF REVIEW: The addition of lateral extra-articular tenodesis (LET) to anterior cruciate ligament (ACL) reconstruction (ACLR) has become increasingly popular to address residual rotatory knee instability. The purpose of this article is to review the anatomy and biomechanics of the anterolateral complex (ALC) of the knee, outline different LET techniques, and provide biomechanical and clinical evidence for its use as an augmentation procedure with ACLR. RECENT FINDINGS: Rotatory knee instability has been identified as a common contributor to ACL rupture in both the primary and revision settings. Several biomechanical studies have shown that LET reduces strain on the ACL by decreasing excess tibial translation and rotation. Additionally, in vivo studies have demonstrated restoration of side-to-side differences in anterior-posterior knee translation, higher rates of return to play, and overall increased patient satisfaction following combined ACLR and LET. As a result, various LET techniques have been developed to help offload the ACL graft and lateral compartment of the knee. However, conclusions are limited by a lack of concrete indications and contraindications for use of LET in the clinical setting. SUMMARY: Recent studies have shown that rotatory knee instability contributes to native ACL and ACL graft rupture and LET may provide further stability to reduce rates of failure. Further investigation is needed to establish concrete indications and contraindications to determine which patients would most benefit from added stability of the ALC.

Introduction A long T2 relaxation time can reflect oedema, and myocardial inflammation when combined with increased plasma troponin levels. Cardiovascular magnetic resonance (CMR) T2 mapping therefore has potential to provide a key diagnostic and prognostic biomarkers. However, T2 varies by scanner, software, and sequence, highlighting the need for standardization and for a quality assurance system for T2 mapping in CMR. Aim To fabricate and assess a phantom dedicated to the quality assurance of T2 mapping in CMR. Method A T2 mapping phantom was manufactured to contain 9 T1 and T2 (T1|T2) tubes to mimic clinically relevant native and post-contrast T2 in myocardium across the health to inflammation spectrum (i.e., 43–74 ms) and across both field strengths (1.5 and 3 T). We evaluated the phantom’s structural integrity, B0 and B1 uniformity using field maps, and temperature dependence. Baseline reference T1|T2 were measured using inversion recovery gradient echo and single-echo spin echo (SE) sequences respectively, both with long repetition times (10 s). Long-term reproducibility of T1|T2 was determined by repeated T1|T2 mapping of the phantom at baseline and at 12 months. Results The phantom embodies 9 internal agarose-containing T1|T2 tubes doped with nickel di-chloride (NiCl2) as the paramagnetic relaxation modifier to cover the clinically relevant spectrum of myocardial T2. The tubes are surrounded by an agarose-gel matrix which is doped with NiCl2 and packed with high-density polyethylene (HDPE) beads. All tubes at both field strengths, showed measurement errors up to ≤ 7.2 ms [2 by balanced steady-state free precession T2 mapping compared to reference SE T2 with the exception of the post-contrast tube of ultra-low T1 where the deviance was up to 16 ms [40.0%]. At 12 months, the phantom remained free of air bubbles, susceptibility, and off-resonance artifacts. The inclusion of HDPE beads effectively flattened the B0 and B1 magnetic fields in the imaged slice. Independent temperature dependency experiments over the 13–38 °C range confirmed the greater stability of shorter vs longer T1|T2 tubes. Excellent long-term (12-month) reproducibility of measured T1|T2 was demonstrated across both field strengths (all coefficients of variation Conclusion The T2 mapping phantom demonstrates excellent structural integrity, B0 and B1 uniformity, and reproducibility of its internal tube T1|T2 out to 1 year. This device may now be mass-produced to support the quality assurance of T2 mapping in CMR.

Most clinical trials evaluating COVID-19 therapeutics include assessments of antiviral activity. In recently completed outpatient trials, changes in nasal SARS-CoV-2 RNA levels from baseline were commonly assessed using analysis of covariance (ANCOVA) or mixed models for repeated measures (MMRM) with single-imputation for results below assay lower limits of quantification (LLoQ). Analyzing changes in viral RNA levels with singly-imputed values can lead to biased estimates of treatment effects. In this paper, using an illustrative example from the ACTIV-2 trial, we highlight potential pitfalls of imputation when using ANCOVA or MMRM methods, and illustrate how these methods can be used when considering values

Data sharing: The PHOSP-COVID study protocol, consent form, definition, and derivation of clinical characteristics and outcomes, training materials, regulatory documents, information about requests for data access, and other relevant study materials are available online. UK Biobank information can be released once necessary approvals have been obtained. Other data (eg, the R code and protocol) will be made available on reasonable request to the corresponding author. Copyright © 2023 The Author(s). Background: Sleep disturbance is common following hospital admission both for COVID-19 and other causes. The clinical associations of this for recovery after hospital admission are poorly understood despite sleep disturbance contributing to morbidity in other scenarios. We aimed to investigate the prevalence and nature of sleep disturbance after discharge following hospital admission for COVID-19 and to assess whether this was associated with dyspnoea. Methods: CircCOVID was a prospective multicentre cohort substudy designed to investigate the effects of circadian disruption and sleep disturbance on recovery after COVID-19 in a cohort of participants aged 18 years or older, admitted to hospital for COVID-19 in the UK, and discharged between March, 2020, and October, 2021. Participants were recruited from the Post-hospitalisation COVID-19 study (PHOSP-COVID). Follow-up data were collected at two timepoints: an early time point 2–7 months after hospital discharge and a later time point 10–14 months after hospital discharge. Sleep quality was assessed subjectively using the Pittsburgh Sleep Quality Index questionnaire and a numerical rating scale. Sleep quality was also assessed with an accelerometer worn on the wrist (actigraphy) for 14 days. Participants were also clinically phenotyped, including assessment of symptoms (ie, anxiety [Generalised Anxiety Disorder 7-item scale questionnaire], muscle function [SARC-F questionnaire], dyspnoea [Dyspnoea-12 questionnaire] and measurement of lung function), at the early timepoint after discharge. Actigraphy results were also compared to a matched UK Biobank cohort (non-hospitalised individuals and recently hospitalised individuals). Multivariable linear regression was used to define associations of sleep disturbance with the primary outcome of breathlessness and the other clinical symptoms. PHOSP-COVID is registered on the ISRCTN Registry (ISRCTN10980107). Findings: 2320 of 2468 participants in the PHOSP-COVID study attended an early timepoint research visit a median of 5 months (IQR 4–6) following discharge from 83 hospitals in the UK. Data for sleep quality were assessed by subjective measures (the Pittsburgh Sleep Quality Index questionnaire and the numerical rating scale) for 638 participants at the early time point. Sleep quality was also assessed using device-based measures (actigraphy) a median of 7 months (IQR 5–8 months) after discharge from hospital for 729 participants. After discharge from hospital, the majority (396 [62%] of 638) of participants who had been admitted to hospital for COVID-19 reported poor sleep quality in response to the Pittsburgh Sleep Quality Index questionnaire. A comparable proportion (338 [53%] of 638) of participants felt their sleep quality had deteriorated following discharge after COVID-19 admission, as assessed by the numerical rating scale. Device-based measurements were compared to an age-matched, sex-matched, BMI-matched, and time from discharge-matched UK Biobank cohort who had recently been admitted to hospital. Compared to the recently hospitalised matched UK Biobank cohort, participants in our study slept on average 65 min (95% CI 59 to 71) longer, had a lower sleep regularity index (–19%; 95% CI –20 to –16), and a lower sleep efficiency (3·83 percentage points; 95% CI 3·40 to 4·26). Similar results were obtained when comparisons were made with the non-hospitalised UK Biobank cohort. Overall sleep quality (unadjusted effect estimate 3·94; 95% CI 2·78 to 5·10), deterioration in sleep quality following hospital admission (3·00; 1·82 to 4·28), and sleep regularity (4·38; 2·10 to 6·65) were associated with higher dyspnoea scores. Poor sleep quality, deterioration in sleep quality, and sleep regularity were also associated with impaired lung function, as assessed by forced vital capacity. Depending on the sleep metric, anxiety mediated 18–39% of the effect of sleep disturbance on dyspnoea, while muscle weakness mediated 27–41% of this effect. Interpretation: Sleep disturbance following hospital admission for COVID-19 is associated with dyspnoea, anxiety, and muscle weakness. Due to the association with multiple symptoms, targeting sleep disturbance might be beneficial in treating the post-COVID-19 condition. Funding: UK Research and Innovation, National Institute for Health Research, and Engineering and Physical Sciences Research Council. UK Research and Innovation, National Institute for Health Research, and Engineering and Physical Sciences Research Council.

SARS-CoV-2 (COVID-19) has caused over 80 million infections 973,000 deaths in the United States, and mutations are linked to increased transmissibility. This study aimed to determine the effect of SARS-CoV-2 variants on respiratory features, mortality, and to determine the effect of vaccination status. A retrospective review of medical records (n = 55,406 unique patients) using the University of California Health COvid Research Data Set (UC CORDS) was performed to identify respiratory features, vaccination status, and mortality from 01/01/2020 to 04/26/2022. Variants were identified using the CDC data tracker. Increased odds of death were observed amongst unvaccinated individuals and fully vaccinated, partially vaccinated, or individuals who received any vaccination during multiple waves of the pandemic. Vaccination status was associated with survival and a decreased frequency of many respiratory features. More recent SARS-CoV-2 variants show a reduction in lower respiratory tract features with an increase in upper respiratory tract features. Being fully vaccinated results in fewer respiratory features and higher odds of survival, supporting vaccination in preventing morbidity and mortality from COVID-19.

We propose a novel approach to the estimation of multiple Gaussian graphical models (GGMs) to analyse patterns of association among a set of metabolites, under different conditions. Our motivating application is the SABRE (Southall And Brent REvisited) study, a triethnic cohort study conducted in the United Kingdom. Through joint modelling of pattern of association corresponding to different ethnic groups, we are able to identify potential ethnic differences in metabolite levels and associations, with the aim of gaining a better understanding of different risk of cardiometabolic disorders across ethnicities. We model the relationship between a set of metabolites and a set of covariates through a sparse seemingly unrelated regressions model and we use GGMs to represent the conditional dependence structure among metabolites. We specify a dependent generalised Dirichlet process prior on the edge inclusion probabilities to borrow strength across groups and we adopt the horseshoe prior to identify important biomarkers. Inference is performed via Markov chain Monte Carlo.

Few studies have analyzed mortality rates among transgender (trans) populations in the United States and compared them to the rates of non-trans populations. Using private insurance data from 2011 to 2019, we estimated age-specific all-cause mortality rates among a subset of trans people enrolled in private insurance and compared them to a 10% randomly selected non-trans cohort. Overall, we found that trans people were nearly twice as likely to die over the period as their non-trans counterparts. When stratifying by gender, we found key disparities within trans populations, with people on the trans feminine to nonbinary spectrum being at the greatest risk of mortality compared to non-trans males and females. While we found that people on the trans masculine to nonbinary spectrum were at a similar risk of overall mortality compared to non-trans females, their overall mortality rate was statistically smaller than that of non-trans males. These findings provide evidence that some trans and non-trans populations experience substantially different mortality conditions across the life course and necessitate further study.

Background/Purpose: Telehealth has evolved over the past several decades to address varying medical needs. Most recently, it has been widely utilized as a result of the COVID-19 pandemic. Most previous studies have not performed in-depth analyses of patient satisfaction with telehealth technologies. This project investigated patient satisfaction with the abrupt implementation of telemedicine within pediatric surgical subspecialties during the COVID-19 pandemic. Materials and Methods: We conducted a single-center review to determine patients' satisfaction with telemedicine during the early stages of the pandemic. Surveys were distributed to patients who completed a telemedicine video visit within a pediatric surgical subspecialty at Connecticut Children's Medical Center between March 16 and May 16, 2020. Results: A total of 1,608 patients were contacted, with 457 surveys completed (28.4%). Of all respondents, 95.6% were "very satisfied" or "satisfied" with their overall telemedicine appointment. Seventy-three percent reported no difficulty with completing their visit. Eighty-seven percent would consider another telemedicine visit again in the future. No significant difference was found between the payor mix for telemedicine and in-person appointments. Conclusions: The implementation of telemedicine at Connecticut Children's Medical Center during the COVID-19 pandemic was successful despite numerous barriers to use. Families not only showed high rates of satisfaction with the overall visit and provider interaction, but also an overwhelming openness to future use of telehealth.

To determine the in vivo effects of superior capsule reconstruction (SCR) on glenohumeral kinematics during abduction and to compare those kinematics results with patient-reported outcomes, range of motion, and strength.Dynamic biplane radiography was used to image 10 patients with irreparable rotator cuff tears while performing scapular plane abduction pre- and 1-year post-surgery. Shoulder kinematics were determined by matching subject-specific computed tomography-based bone models to the radiographs using a validated tracking technique.No change was detected in static acromiohumeral distance (-0.7 ± 2.1 mm; P = .35); however, average dynamic acromiohumeral distance decreased (2.7 ± 1.2 mm to 2.3 ± 1.0 mm; P = .035) from pre- to 1-year post-surgery, respectively. The humeral head position was 0.5 ± 0.5 mm more superior 1-year post-surgery compared with pre-surgery (P = .01). Glenohumeral abduction increased from pre-surgery (150 ± 20°) to 1-year post-surgery (165 ± 10°) (P = .04) and all patient-reported outcomes improved from pre-surgery to 1-year post-surgery (all P.002). A more posterior shift in humeral head position was associated with improved American Shoulder and Elbow Surgeons Shoulder Score from pre-surgery to 1-year post-surgery (r = 0.71, P = .02).These data suggest that SCR may not depress the humeral head during functional abduction, as previously postulated, and postoperative improvements in subjective and clinical outcomes may be affected by mechanisms other than changes in shoulder kinematics.In vivo kinematics changes after SCR are small and do not correspond to previously postulated changes.

Introduction. The Oncotype DX test is a genomic assay that generates a Recurrence Score (RS) predicting the 10-year risk of recurrence and response to adjuvant chemotherapy in ER+/HER2− breast cancer patients. The aims were to determine breast cancer distant recurrence and correlate with adjuvant chemoendocrine prescribing patterns based on the Oncotype DX recurrence score. Methods. We conducted a retrospective single-institution case series of 71 patients who had Oncotype DX assay testing after definitive surgery between 2012 and 2016. Both node-positive and node-negative patients were included. Patients were divided into Oncotype DX low risk (RS 25) (n = 16, 23%). Median follow-up was 6.1 years (range 4–8.9 years). Adjuvant treatment regimens and oncological outcomes were determined. Results. Mean age at diagnosis was 56 years (range, 33–77). Invasive ductal carcinoma (IDC) accounted for the majority (87%), with most tumors measuring between 10–20 mm (52%). 48% of the cohort were node positive. 15 of 16 high-risk patients (94%) received chemotherapy. 96% of intermediate-risk patients received endocrine therapy alone, one patient received chemoendocrine therapy (2%), and one declined systemic therapy (2%). In the low-risk group, 100% received endocrine therapy only. The high-risk group had the lowest mean ER% ( P < 0.05 ), greatest mean mitotic rate ( P < 0.05 ), and greatest proportion of Ki67% > 14. Five patients developed distant recurrence (7%): three from the intermediate-risk group (7%), one from the low-risk group (10%), and one from the high-risk group (6%). Conclusion. This is the first Australian study reporting the experience with medium-term recurrence outcomes of using the Oncotype DX assay in breast cancer. Chemotherapy was rarely given for patients with low-to-intermediate RS and always offered in high RS. This pattern of prescribing was associated with low rates of distant recurrence. National funding models should be considered.

Correct placement of the femoral and tibial tunnels in the anatomic footprint during anterior cruciate ligament reconstruction (ACLR) is paramount for restoring rotatory knee stability. Recent studies have looked at surgeon volume and its outcomes on procedures such as total knee arthroplasty and infection rates, but only few studies have specifically examined tunnel placement after ACLR based on surgeon volume. The purpose of this study was to compare the placement of femoral and tibial tunnels during ACLR between high-volume and low-volume surgeons. It was hypothesized that high-volume surgeons would have more anatomic tunnel placement compared with low-volume surgeons.A retrospective review of all ACLR performed between 2015 and 2019 at an integrated health care system consisting of both academic and community hospitals with 68 orthopaedic surgeons was conducted. Surgeon volume was categorized as less than 35 ACLR per year (low volume) and 35 or more ACLR per year (high volume). Femoral tunnel placement for each patient was determined using an exact strict lateral radiograph (less than 6 mm of offset between the posterior halves of the medial and lateral condyles) taken after the primary ACLR using the quadrant method. The centre of the femoral tunnel was measured in relation to the posterior-anterior (PA) and proximal-distal (PD) dimensions (normal centre of anatomic footprint: PA 25% and PD 29%). Tibial tunnel placement for each patient was determined on the same lateral radiographs by measuring the mid-sagittal tibial diameter and the centre of the tibial attachment area of the ACL from the anterior tibial margin (normal centre of anatomic footprint: 43%). Each lateral radiograph was reviewed by one of two blinded reviewers.A total of 4500 patients were reviewed, of which 645 patients met all the inclusion/exclusion criteria and were included in the final analysis. There were 228 patients in the low-volume group and 417 patients in the high-volume group. Low-volume surgeons performed a mean of 5 ACLRs per year, whereas surgeons in the high-volume group performed a mean of 40 ACLRs per year. In the PA dimension, the low-volume group had significantly more anterior femoral tunnel placement compared with the high-volume group (32 ± 10% vs 28 ± 9%, p 0.01). In the PD dimension, the low-volume group had statistically significant more proximal femoral tunnel placement compared to the high-volume group (32 ± 9% vs 35 ± 9%, p 0.01). For the tibial tunnel, the low-volume group had significantly more posterior tibial tunnel placement compared with the high-volume group (41 ± 10% vs 38 ± 7%, p 0.01).Low-volume surgeons placed their femoral tunnels significantly more anterior and proximal (high) during ACLR, and placed their tibial tunnels significantly more posterior, compared with high-volume surgeons. Prior research has indicated that anatomic placement of the femoral and tibial tunnels during ACLR leads to improved rotatory knee stability. The findings of this study demonstrate the importance of surgical volume and experience during ACLR.III.

OBJECTIVE The objective of this study was to determine the frequency with which brain biopsy for presumed CNS relapse of systemic hematological malignancies yields new, actionable diagnostic information. Hematological malignancies represent a disparate group of genetic and histopathological disorders. Proclivity for brain involvement is dependent on the unique entity and may occur synchronously or metasynchronously with the systemic lesion. Diffuse large B-cell lymphomas (DLBCLs) have a high propensity for brain involvement. Patients in remission from systemic DLBCL may present with a lesion suspicious for brain relapse. These patients often undergo brain biopsy. The authors’ a priori hypothesis was that brain biopsy in patients with a history of systemic DLBCL and a new brain MRI lesion would have lower diagnostic utility compared with patients with non-DLBCL systemic malignancies. METHODS The authors performed a retrospective review of patients who underwent brain biopsy between 2000 and 2019. Inclusion criteria were patients ≥ 18 years of age with a prior systemic hematological malignancy in remission presenting with a new brain MRI lesion concerning for CNS relapse. Patients with a history of any CNS neoplasms, demyelinating disorders, or active systemic disease were excluded. The main outcome was the proportion of patients with a distinct histopathological brain diagnosis compared with the systemic malignancy. The authors secondarily assessed overall survival, procedure-related morbidity, and 30-day mortality. RESULTS Sixty patients met inclusion criteria (40 males and 20 females); the median age at brain biopsy was 67 years (range 23–88 years). The median follow-up was 8.5 months (range 0.1–231 months). Thirty-nine (65.0%) patients had DLBCL and 21 (35%) had non-DLBCL malignancies. Thirty-five of 36 (97.2%) patients with prior systemic DLBCL and a diagnostic biopsy had histopathological confirmation of the original systemic disease versus 0 of 21 patients with non-DLBCL systemic malignancies (p < 0.001). Morbidity and 30-day mortality were 8.3% and 10.0%, respectively; 2 of 6 30-day mortalities were directly attributable to the biopsy. The median overall survival following brain biopsy was 10.8 months. CONCLUSIONS Patients with a history of systemic DLBCL and presumed CNS relapse gained minimal clinical benefit from brain biopsy but were at high risk of morbidity and mortality. In patients with a history of non-DLBCL systemic malignancies, brain biopsy remained critical given the high likelihood for discovery of distinct diagnostic entities. It was determined that patients with a prior systemic DLBCL and presumed brain relapse should likely receive empirical therapy obviating treatment delay and the risks of brain biopsy.

Craniosynostosis involves the premature fusion of 1 or more cranial sutures and commonly presents as an isolated, nonsyndromic diagnosis. A subset of patients have syndromic craniosynostosis. Several unique considerations must be taken into account when managing patients with syndromic craniosynostosis. A multidisciplinary craniofacial team with a central coordinator is particularly useful for coordinating care among various specialists, and close monitoring is mandatory owing to the increased risk of intracranial hypertension. Surgical management varies among centers, but core options include fronto-orbital advancement with cranial vault remodeling, posterior vault expansion, endoscopic-assisted suturectomy with postoperative orthotic therapy, and midface advancement.

The purpose of this study was to determine the intrasession reliability of countermovement jump (CMJ) braking and propulsive phase variables in youth athletes. Thirty youth athletes between the age of 10- and 16-years volunteered to take part in this study. All participants performance 3 CMJ trials on a force platform. Thirteen of 16 CMJ variables were found to have acceptable absolute reliability in the pre-PHV group (CV% = 3.51-9.96) whilst the circa-PHV group contained 10 variables demonstrating acceptable absolute reliability (CV% = 2.37-9.67). Almost all variables (14 out of 16) in the post-PHV group were found to have acceptable absolute reliability (CV% = 2.59-9.61). Mean and peak braking RFD displayed poor absolute reliability in all maturity groups (CV% = 10.89-21.55). Time to take-off, braking and propulsive phase time and propulsive impulse demonstrated the largest differences between pre- and circa-PHV groups (p < 0.005; d > 0.95). Braking phase time, peak and mean braking force, mean braking power and RSImod demonstrated the biggest differences between the circa- and post-PHV groups (p < 0.001; d > 1.81). The poorest reliability scores were found in the circa-PHV group, demonstrating the need for additional familiarisation at this stage of maturity.

BackgroundAtherosclerotic cardiovascular disease (ASCVD) risk differs by ethnicity. In comparison with Europeans (EA) South Asian (SA) people in UK experience higher risk of coronary heart disease (CHD) and stroke, while African Caribbean people have a lower risk of CHD but a higher risk of stroke.AimTo compare carotid atherosclerosis in EA, SA, and AC participants in the Southall and Brent Revisited (SABRE) study and establish if any differences were explained by ASCVD risk factors.MethodsCardiovascular risk factors were measured, and carotid ultrasound was performed in 985 individuals (438 EA, 325 SA, 228 AC). Carotid artery plaques and intima-media thickness (cIMT) were measured. Associations of carotid atherosclerosis with ethnicity were investigated using generalised linear models (GLMs), with and without adjustment for non-modifiable (age, sex) and modifiable risk factors (education, diabetes, hypertension, total cholesterol, HDL-C, alcohol consumption, current smoking).ResultsPrevalence of any plaque was similar in EA and SA, but lower in AC (16, 16, and 6%, respectively; p < 0.001). In those with plaque, total plaque area, numbers of plaques, plaque class, or greyscale median did not differ by ethnicity; adjustment for risk factors had minimal effects. cIMT was higher in AC than the other ethnic groups after adjustment for age and sex, adjustment for risk factors attenuated this difference.ConclusionPrevalence of carotid artery atherosclerotic plaques varies by ethnicity, independent of risk factors. Lower plaque prevalence in in AC is consistent with their lower risk of CHD but not their higher risk of stroke. Higher cIMT in AC may be explained by risk factors. The similarity of plaque burden in SA and EA despite established differences in ASCVD risk casts some doubt on the utility of carotid ultrasound as a means of assessing risk across these ethnic groups.

Background Higher concentrations of cholesterol-containing low-density lipoprotein (LDL-C) increase the risk of cardiovascular disease (CVD). The association of LDL-C with non-CVD traits remains unclear, as are the possible independent contributions of other cholesterol-containing lipoproteins and apolipoproteins. Methods Nuclear magnetic resonance spectroscopy was used to measure the cholesterol content of high density (HDL-C), very low-density (VLDL-C), intermediate-density (IDL-C), as well as low-density lipoprotein fractions, the apolipoproteins Apo-A1 and Apo-B, as well as total triglycerides (TG), remnant-cholesterol (Rem-Chol) and total cholesterol (TC). The causal effects of these exposures were assessed against 33 outcomes using univariable and multivariable Mendelian randomization (MR). Results The majority of cholesterol containing lipoproteins and apolipoproteins affect coronary heart disease (CHD), carotid intima-media thickness, carotid plaque, C-reactive protein (CRP) and blood pressure. Multivariable MR indicated that many of these effects act independently of HDL-C, LDL-C and TG, the most frequently measured lipid fractions. Higher concentrations of TG, VLDL-C, Rem-Chol and Apo-B increased heart failure (HF) risk; often independently of LDL-C, HDL-C or TG. Finally, a subset of these exposures associated with non-CVD traits such as Alzheimer’s disease (AD: HDL-C, LDL-C, IDL-C, Apo-B), type 2 diabetes (T2DM: VLDL-C, IDL-C, LDL-C), and inflammatory bowel disease (IBD: LDL-C, IDL-C). Conclusions The cholesterol content of a wide range of lipoprotein and apolipoproteins associate with measures of atherosclerosis, blood pressure, CRP, and CHD, with a subset affecting HF, T2DM, AD and IBD risk. Many of the observed effects appear to act independently of LDL-C, HDL-C, and TG, supporting the targeting of lipid fractions beyond LDL-C for disease prevention. UK Biobank was established by the Wellcome Trust medical charity, Medical Research Council, Department of Health, Scottish Government, and the Northwest Regional Development Agency. It has also had funding from the Welsh Assembly Government and the British Heart Foundation. AFS is supported by British Heart Foundation (BHF) grant PG/18/5033837, PG/22/10989 and the UCL BHF Research Accelerator AA/18/6/34223. CF and AFS received additional support from the National Institute for Health Research University College London Hospitals Biomedical Research Centre. MGM is supported by a BHF Fellowship FS/17/70/33482. ADH and DAL (NF-0616-10102) are an NIHR Senior Investigators. This work was funded by the Strategic Priority Fund “Tackling multimorbidity at scale” programme [MR/V033867/1] delivered by the Medical Research Council and the National Institute for Health and Care Research in partnership with the Economic and Social Research Council and in collaboration with the Engineering and Physical Sciences Research Council. The UCLEB Consortium is supported by a British Heart Foundation Programme Grant (RG/10/12/28456). DAL’s contribution to this research is supported by the Bristol BHF Accelerator Award (AA/18/1/34219), her BHF Chair (CH/F/20/90003) and the UK Medical Research Council (MC_UU_00011/1-6). MK is supported by the UK Medical Research Council (MRC MR/R024227/1), National Institute on Aging (NIA), US (R01AG056477), and the Wellcome Trust (221854/Z/20/Z). PC is supported by the Thailand Research Fund (MRG6280088). TRG receives funding from the UK Medical Research Council as part of the MRC Integrative Epidemiology Unit (MC_UU_00011/4). AH receives support from the British Heart Foundation (SP/F/21/150020) and UK Medical Research Council (MC_PC-20051). ADH receives support from the UK Medical Research Council (MC_UU_12019/1). NF received funding from the National Health Institutes (MD012765, DK117445). CG has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 754490—MINDED project.