Contribution of mutant HSC clones to immature and mature cells in MDS and CMML, and variations with AZA therapy.

Myelodysplastic neoplasms (MDSs) and chronic myelomonocytic leukemia (CMML) are clonal disorders driven by progressively acquired somatic mutations in hematopoietic stem cells (HSCs). Hypomethylating agents (HMAs) can modify the clinical course of MDS and CMML. Clinical improvement does not require eradication of mutated cells and may be related to improved differentiation capacity of mutated HSCs. However, in patients with established disease it is unclear whether (1) HSCs with multiple mutations progress through differentiation with comparable frequency to their less mutated counterparts or (2) improvements in peripheral blood counts following HMA therapy are driven by residual wild-type HSCs or by clones with particular combinations of mutations. To address these questions, the somatic mutations of individual stem cells, progenitors (common myeloid progenitors, granulocyte monocyte progenitors, and megakaryocyte erythroid progenitors), and matched circulating hematopoietic cells (monocytes, neutrophils, and naïve B cells) in MDS and CMML were characterized via high-throughput single-cell genotyping, followed by bulk analysis in immature and mature cells before and after AZA treatment. The mutational burden was similar throughout differentiation, with even the most mutated stem and progenitor clones maintaining their capacity to differentiate to mature cell types in vivo. Increased contributions from productive mutant progenitors appear to underlie improved hematopoiesis in MDS following HMA therapy.

Occupational exposure to extremely low-frequency magnetic fields and follicular lymphoma risk: a family case-control study.

OBJECTIVES: We aimed to examine the relationship between occupational exposure to extremely low-frequency magnetic fields (ELF-MFs) and follicular lymphoma (FL) risk. METHODS: We conducted a family case-control study between 2011 and 2016 in Australia and included 681 cases. Controls were either a family member of cases (related (n=294), unrelated (n=179)) or were unrelated recruited for a similarly designed Australian multiple myeloma study (n=711). We obtained detailed job histories using lifetime work calendars. We assigned exposure to ELF-MFs using an enhanced job exposure matrix, with a lag period of 10 years. We examined associations with FL risk using logistic regression accounting for relatedness between cases and controls. We performed sensitivity analyses including by control type, by sex, complete case analyses, ELF-MF exposure percentiles in addition to quartiles, ELF-MF exposure in the maximum exposed job, a shorter lag period (1 year) and the cumulative exposure in the most recent time period (1-9 years). RESULTS: We observed no association with the average intensity, duration or lifetime cumulative exposure to occupational ELF-MF exposure in the primary or sensitivity analyses. CONCLUSIONS: Our findings do not support an association between occupational ELF-MF exposure and FL risk. Although the inclusion of family members as part of the larger control group may have biased our risk estimates towards the null, findings were similar in sensitivity analyses restricted to cases and unrelated controls. Further research incorporating enhanced exposure assessment to ELF-MF is warranted to inform occupational safety regulations and any potential role in lymphomagenesis.

Using Virtual Reality to Enhance Food Technology Education.

The use of Virtual Reality (VR) technology combined with 360-degree images and videos provide an opportunity for teachers to bring students into the classroom even when they are located somewhere else. During the COVID-19 lockdown and pandemic, with students across the world forced into home-based learning via remote teaching, a VR classroom shows potential as a tool for adding depth to their learning. The possibility of immersing students in a virtual environment could provide an answer to motivation and engagement issues for today's students as well as a solution to some of the current constraints faced by teachers. In particular, VR has the potential to increase the time students are able to spend in (virtual) environments that are suitable for teaching and learning practical skills. With the cost of VR equipment reducing rapidly and the increasing quality of virtual experiences, it appears VR is on the tipping-point of becoming a regular part of school programmes.This article outlines the development and testing of a VR Classroom for the delivery of a food-based lesson with middle school students in a New Zealand school. Kitchens are a costly commodity for schools and the obvious health and safety issues make teaching practical cooking skills challenging. With a focus on student engagement and motivation, data is collected from observation of students using the virtual classroom and a post-test survey. Results show that students were highly motivated and perceived the VR classroom as fun to use.

The NSW Pathology Atlas of Variation: Part I-Identifying Emergency Departments With Outlying Laboratory Test-Ordering Practices.

STUDY OBJECTIVE: Abdominal pain and chest pain are leading reasons for emergency department (ED) presentations, with laboratory tests frequently ordered to aid the diagnostic process. Our study aims to identify EDs with outlying laboratory ordering practices for patients presenting with undifferentiated abdominal pain and chest pain. METHODS: This was a retrospective observational study of 519,597 patients who presented with the complaint of abdominal or chest pain at 44 major hospital EDs across New South Wales, Australia, from January 2017 to September 2018. For each condition, we evaluated the risk-adjusted rate of ordering at least 1 laboratory test and of each of the top 15 ordered tests. We used funnel plots to graph variations in test ordering and identify EDs with outlying test-ordering practices. EDs lying above or below the 99.8% funnel control limits were regarded as outliers. RESULTS: From 3,360,152 unplanned presentations, abdominal pain and chest pain represented 8.8% (n=296,809) and 6.6% (n=222,788) of all cases, respectively. No major outliers were observed for ordering at least one laboratory test; however, variations were observed for individual tests. For abdominal pain, the top 3 tests with the highest ordering variation included glucose (20 outlier EDs), C-reactive protein (10 outliers), and calcium-magnesium-phosphate (7 outliers). For chest pain, the top 3 tests with the highest ordering variation were glucose (21 outlier EDs), C-reactive protein (17 outliers), and liver function test (14 outliers). CONCLUSION: Identifying EDs with outlying laboratory-ordering practices is the first step in initiating context-specific evaluation of whether outlying variations are unwarranted.

The NSW Pathology Atlas of Variation: Part II-The Association of Variation in Emergency Department Laboratory Investigations With Outcomes for Patients Presenting With Chest Pain.

STUDY OBJECTIVE: Laboratory test use varies across emergency departments (EDs), yet little is known about the effect of this variation on outcomes. The aim of this study is 2-fold: to stratify EDs into clusters based on similar test use, and to determine whether the clusters differ in patient operational outcomes among patients presenting to EDs with undifferentiated chest pain. METHODS: We conducted a retrospective cohort study of 222,788 patients presenting with undifferentiated chest pain at 44 EDs across New South Wales, Australia, from January 2017 to September 2018. The operational outcomes measured in this study included ED length of stay, hospital admission, the Emergency Treatment Performance target, and 7- and 15-day all-cause and same-cause ED revisit rates. We performed a hierarchic cluster analysis to identify ED clusters and mixed-effects models to determine the association between the clusters and the operational outcomes. RESULTS: Two ED clusters, moderate users (18 EDs) and high users (26 EDs), were identified. After adjustment for confounders, the median ED length of stay was greater by 15.7% (equivalent to 33.4 minutes) in high versus moderate users (95% confidence interval 6.62 to 25.52 minutes), and high users were less likely to achieve the Emergency Treatment Performance target versus moderate users (odds ratio 0.66; 95% confidence interval 0.50 to 0.86). There were no significant differences between the users in hospital admission and ED revisit rates. CONCLUSION: Our findings suggest that reducing test use may reduce ED length of stay and improve the chance of achieving the Emergency Treatment Performance target.

Potentially redundant repeat liver function test ordering practices in australian hospitals: A 5-year multicentre retrospective observational study.

BACKGROUND: Repeat Liver Function Tests (LFTs) are often necessary for monitoring purposes, but retesting within a short time interval may suggest potentially redundant repeat test (PRRT) ordering practices. We aimed to determine the proportion of potentially redundant repeat LFT ordering and identify associated factors in hospitals. METHODS: A 5-year (2014-2018) retrospective cohort study in six hospitals in New South Wales, Australia. A total of 131 885 patient admissions with repeat LFTs in the general ward (n = 102 852) and intensive care unit (ICU) (n = 29 033) met the inclusion criteria. Existing guidelines do not support retesting LFT for at least 48-72 hours. We used 24 hours as a conservative minimum retesting interval to examine PRRT ordering. We fit binary logistic regression to identify factors associated with PRRT ordering in two conditions with the highest repeat LFTs. RESULTS: There were a total of 298 567 repeat LFTs (medians of 2 repeats/admission and retesting interval of 25.6 hours) in the general ward and 205 929 (medians of 4 repeats/admission and retesting interval of 24.1 hours) in the ICU. The proportions of PRRT ordering were 35.2% (105 227/298 567) and 47.7% (98 307/205 929) in the general ward and ICU, respectively. The proportions of patients who received at least one PRRT were 52.3% (53 766/102 852) and 83.9% (24 365/29 033) in the general ward and ICU, respectively. Age, gender and the number of comorbidities and procedures were associated with the likelihood of ordering PRRT depending on the settings. CONCLUSION: Repeat LFT testing is common in Australian hospitals, often within 24 hours, despite guidelines not supporting too-early repeat testing. Further research should be conducted to understand whether better adherence to existing guidelines is required, or if there is any case for guidelines to be updated based on certain patient subpopulations.

Evaluation of the accuracy of diagnostic coding for influenza compared to laboratory results: the availability of test results before hospital discharge facilitates improved coding accuracy.

BACKGROUND: Assessing the accuracy of diagnostic coding is essential to ensure the validity and reliability of administrative coded data. The aim of the study was to evaluate the accuracy of assigned International Classification of Diseases version 10-Australian Modification (ICD-10-AM) codes for influenza by comparing with patients' results of their polymerase chain reaction (PCR)-based laboratory tests. METHOD: A retrospective study was conducted across seven public hospitals in New South Wales, Australia. A total of 16,439 patients who were admitted and tested by either cartridge-based rapid PCR or batched multiplex PCR between January 2016 and December 2017 met the inclusion criteria. We calculated the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of ICD-10-AM coding using laboratory results as a gold standard. Separate analyses were conducted to determine whether the availability of test results at the time of hospital discharge influenced diagnostic coding accuracy. RESULTS: Laboratory results revealed 2759 positive influenza cases, while ICD-10-AM coding identified 2527 patients. Overall, 13.7% (n = 378) of test positive patients were not assigned an ICD-10-AM code for influenza. A further 5.8% (n = 146) patients with negative test results were incorrectly assigned an ICD-10-AM code for influenza. The sensitivity, specificity, PPV and NPV of ICD-10-AM coding were 93.1%; 98.9%; 94.5% and 98.6% respectively when test results were received before discharge and 32.7%; 99.2%; 87.8% and 89.8% respectively when test results were not available at discharge. The sensitivity of ICD-10-AM coding varied significantly across hospitals. The use of rapid PCR or hospitalisation during the influenza season were associated with greater coding accuracy. CONCLUSION: Although ICD-10-AM coding for influenza demonstrated high accuracy when laboratory results were received before discharge, its sensitivity was substantially lower for patients whose test results were not available at discharge. The timely availability of laboratory test results during the episode of care could contribute to improved coding accuracy.

Improved Position Accuracy of Foot-Mounted Inertial Sensor by Discrete Corrections from Vision-Based Fiducial Marker Tracking.

In this paper, we present a novel pedestrian indoor positioning system that uses sensor fusion between a foot-mounted inertial measurement unit (IMU) and a vision-based fiducial marker tracking system. The goal is to provide an after-action review for first responders during training exercises. The main contribution of this work comes from the observation that different walking types (e.g., forward walking, sideways walking, backward walking) lead to different levels of position and heading error. Our approach takes this into account when accumulating the error, thereby leading to more-accurate estimations. Through experimentation, we show the variation in error accumulation and the improvement in accuracy alter when and how often to activate the camera tracking system, leading to better balance between accuracy and power consumption overall. The IMU and vision-based systems are loosely coupled using an extended Kalman filter (EKF) to ensure accurate and unobstructed positioning computation. The motion model of the EKF is derived from the foot-mounted IMU data and the measurement model from the vision system. Existing indoor positioning systems for training exercises require extensive active infrastructure installation, which is not viable for exercises taking place in a remote area. With the use of passive infrastructure (i.e., fiducial markers), the positioning system can accurately track user position over a longer duration of time and can be easily integrated into the environment. We evaluated our system on an indoor trajectory of 250 m. Results show that even with discrete corrections, near a meter level of accuracy can be achieved. Our proposed system attains the positioning accuracy of 0.55 m for a forward walk, 1.05 m for a backward walk, and 1.68 m for a sideways walk with a 90% confidence level.

Impact of Rapid Molecular Diagnostic Testing of Respiratory Viruses on Outcomes of Adults Hospitalized with Respiratory Illness: a Multicenter Quasi-experimental Study.

A standard multiplex PCR offers comprehensive testing for respiratory viruses. However, it has traditionally been performed in a referral laboratory with a lengthy turnaround time, which can reduce patient flow through the hospital. We aimed to determine whether the introduction of a rapid PCR, but with limited targets (Cepheid Xpert Flu/RSV XC), was associated with improved outcomes for adults hospitalized with respiratory illness. A controlled quasi-experimental study was conducted across three hospitals in New South Wales, Australia. Intervention groups received standard multiplex PCR during the preimplementation, July to December 2016 (n = 953), and rapid PCR during the postimplementation, July to December 2017 (n = 1,209). Control groups (preimplementation, n = 937, and postimplementation, n = 1,102) were randomly selected from adults hospitalized with respiratory illness during the same periods. The outcomes were hospital length of stay (LOS) and microbiology test utilization (blood culture, urine culture, sputum culture, and respiratory bacterial and virus serologies). The introduction of rapid PCR was associated with a nonsignificant 8.9-h reduction in median LOS (95% confidence interval [CI], -21.5 h to 3.7 h; P = 0.17) for all patients and a significant 21.5-h reduction in median LOS (95% CI, -36.8 h to -6.2 h; P < 0.01) among patients with positive test results in an adjusted difference-in-differences analysis. For patients receiving test results before disposition, rapid PCR use was associated with a significant reduction in LOS, irrespective of test results. Compared with standard PCR testing, rapid PCR use was significantly associated with fewer blood culture (adjusted odds ratio [aOR], 0.67; 95% CI, 0.5 to 0.82; P < 0.001), sputum culture (aOR, 0.56; 95% CI, 0.47 to 0.68, P < 0.001), bacterial serology (aOR, 0.44; 95% CI, 0.35 to 0.55, P < 0.001) and viral serology (aOR, 0.42; 95% CI, 0.33 to 0.53, P < 0.001) tests, but not with fewer urine culture tests (aOR, 0.94; 95% CI, 0.78 to 1.12, P = 0.48). Rapid PCR testing of adults hospitalized with respiratory illnesses can deliver benefits to patients and reduce resource utilization. Future research should consider a formal economic analysis and assess its potential impacts on clinical decision making.

The impact of rapid molecular diagnostic testing for respiratory viruses on outcomes for emergency department patients.

OBJECTIVE: To determine whether rapid polymerase chain reaction (PCR) testing for influenza and respiratory syncytial viruses (RSV) in emergency departments (EDs) is associated with better patient and laboratory outcomes than standard multiplex PCR testing. DESIGN, SETTING: A before-and-after study in four metropolitan EDs in New South Wales. PARTICIPANTS: 1491 consecutive patients tested by standard multiplex PCR during July-December 2016, and 2250 tested by rapid PCR during July-December 2017. MAIN OUTCOME MEASURES: Hospital admissions; ED length of stay (LOS); test turnaround time; patient receiving test result before leaving the ED; ordering of other laboratory tests. RESULTS: Compared with those tested by standard PCR, fewer patients tested by rapid PCR were admitted to hospital (73.3% v 77.7%; P < 0.001) and more received their test results before leaving the ED (67.4% v 1.3%; P < 0.001); the median test turnaround time was also shorter (2.4 h [IQR, 1.6-3.9 h] v 26.7 h [IQR, 21.2-37.8 h]). The proportion of patients admitted to hospital was also lower in the rapid PCR group for both children under 18 (50.6% v 66.6%; P < 0.001) and patients over 60 years of age (84.3% v 91.8%; P < 0.001). Significantly fewer blood culture, blood gas, sputum culture, and respiratory bacterial and viral serology tests were ordered for patients tested by rapid PCR. ED LOS was similar for the rapid (7.4 h; IQR, 5.0-12.9 h) and standard PCR groups (6.5 h; IQR, 4.2-11.9 h; P = 0.27). CONCLUSION: Rapid PCR testing of ED patients for influenza virus and RSV was associated with better outcomes on a range of indicators, suggesting benefits for patients and the health care system. A formal cost-benefit analysis should be undertaken.

An evaluation of variation in pathology investigations and associated factors for adult patients presenting to emergency departments with chest pain: An observational study.

OBJECTIVE: To determine variation in pathology test ordering practices and identify associated factors for adult patients presenting to emergency departments (ED) with chest pain and subsequently admitted with ischaemic heart disease. METHODS: A retrospective study across six hospital EDs in New South Wales, Australia. A total of 6769 patient presentations between January 2014 and December 2017 met the inclusion criteria. Ordered pathology tests were grouped into three categories based on Australasian College for Emergency Medicine and the Royal College of Pathologists of Australasia recommendations: category I (no restriction in ordering), category II (can be ordered after consulting a supervisor) and category III (not for routine ordering in ED). The primary outcome was the proportion of category III test ordering across study EDs. Factors associated with category III test ordering were identified using a logistic regression. RESULTS: A total of 34 936 pathology tests were ordered: 65.6% (n = 22 932) were category I/II tests and 34.4% (n = 12 004) were category III tests. Five tests (Calcium Magnesium Phosphate, Coagulation Studies, Lipase, C-reactive Protein and Blood Gas tests) accounted for 84.7% of all category III tests. The proportion of category III tests ordered varied by hospitals from 29.8% to 45.9%. The proportion of patients with at least one category III test was 76.3% (range across hospitals: 68.3%-95.6%). Increasing age, presentation to an ED at night, and those in an imminently life-threatening triage category were significantly associated with increased likelihood of category III test ordering. The proportion of category III tests decreased over time. EDs in medium and/or regional hospitals were more likely to order a category III test. CONCLUSION: Pathology investigations for patients presenting with chest pain varied significantly across EDs suggesting opportunities to improve standardisation of test ordering practices.

Retinoic acid regulates embryonic development of mammalian submandibular salivary glands.

Organogenesis is orchestrated by cell and tissue interactions mediated by molecular signals. Identification of relevant signals, and the tissues that generate and receive them, are important goals of developmental research. Here, we demonstrate that Retinoic Acid (RA) is a critical signaling molecule important for morphogenesis of mammalian submandibular salivary glands (SMG). By examining late stage RA deficient embryos of Rdh10 mutant mice we show that SMG development requires RA in a dose-dependent manner. Additionally, we find that active RA signaling occurs in SMG tissues, arising earlier than any other known marker of SMG development and persisting throughout gland morphogenesis. At the initial bud stage of development, we find RA production occurs in SMG mesenchyme, while RA signaling occurs in epithelium. We also demonstrate active RA signaling occurs in glands cultured ex vivo, and treatment with an inhibitor of RA signaling blocks growth and branching. Together these data identify RA signaling as a direct regulator of SMG organogenesis.

Exome sequencing identification of a GJB1 missense mutation in a kindred with X-linked spinocerebellar ataxia (SCA-X1).

We undertook a gene identification and molecular characterization project in a large kindred originally clinically diagnosed with SCA-X1. While presenting with ataxia, this kindred also had some unique peripheral nervous system features. The implicated region on the X chromosome was delineated using haplotyping. Large deletions and duplications were excluded by array comparative genomic hybridization. Exome sequencing was undertaken in two affected subjects. The single identified X chromosome candidate variant was then confirmed to co-segregate appropriately in all affected, carrier and unaffected family members by Sanger sequencing. The variant was confirmed to be novel by comparison with dbSNP, and filtering for a minor allele frequency of <1% in 1000 Genomes project, and was not present in the NHLBI Exome Sequencing Project or a local database at the BCM HGSC. Functional experiments on transfected cells were subsequently undertaken to assess the biological effect of the variant in vitro. The variant identified consisted of a previously unidentified non-synonymous variant, GJB1 p.P58S, in the Connexin 32/Gap Junction Beta 1 gene. Segregation studies with Sanger sequencing confirmed the presence of the variant in all affected individuals and one known carrier, and the absence of the variant in unaffected members. Functional studies confirmed that the p.P58S variant reduced the number and size of gap junction plaques, but the conductance of the gap junctions was unaffected. Two X-linked ataxias have been associated with genetic loci, with the first of these recently characterized at the molecular level. This represents the second kindred with molecular characterization of X-linked ataxia, and is the first instance of a previously unreported GJB1 mutation with a dominant and permanent ataxia phenotype, although different CNS deficits have previously been reported. This pedigree has also been relatively unique in its phenotype due to the presence of central and peripheral neural abnormalities. Other X-linked SCAs with unique features might therefore also potentially represent variable phenotypic expression of other known neurological entities.

Chronic lymphocytic leukaemia, monoclonal B-lymphocytosis and pregnancy: five cases, a literature review and discussion of management.

Chronic lymphocytic leukaemia (CLL) occurs rarely with pregnancy and monoclonal B-Lymphocytosis (MBL) has not previously been described in this setting. CLL is predominantly a disease of the elderly and affects men twice as often as women and hence only an estimated 2% of patients are females of childbearing age. We identified only five reported cases of CLL in pregnancy in the literature. We describe two additional cases, plus three other women with CLL dealing with pregnancy-related decisions. We review the literature and discuss proposals for management and issues that arise in this relatively uncommon occurrence. In contrast to many other haematological malignancies where longer remissions are typically associated with a lower risk of relapse, most patients with CLL who require treatment will ultimately relapse with current therapy. This complex setting requires careful consideration and well informed patients to assist with decisions related to pregnancy.

Mutations in the gene encoding the PML nuclear body protein Sp110 are associated with immunodeficiency and hepatic veno-occlusive disease.

We describe mutations in the PML nuclear body protein Sp110 in the syndrome veno-occlusive disease with immunodeficiency, an autosomal recessive disorder of severe hypogammaglobulinemia, combined T and B cell immunodeficiency, absent lymph node germinal centers, absent tissue plasma cells and hepatic veno-occlusive disease. This is the first report of the involvement of a nuclear body protein in a human primary immunodeficiency and of high-penetrance genetic mutations in hepatic veno-occlusive disease.

Non-Tobacco Nicotine dependence associated with increased Postoperative Complications following Intramedullary Nailing for Intertrochanteric Femur Fractures.

Objectives: Nicotine usage is known to increase postoperative complications; however, studies show that the general population believes that non-tobacco nicotine delivery devices are a safer option compared to tobacco-based nicotine products. This study evaluates postoperative complications between non-tobacco nicotine dependent and non-nicotine dependent patients for intramedullary nailing in intertrochanteric femur fractures. Methods: Utilizing the TriNetX database, we retrospectively examined postoperative outcomes in patients aged 18 to 90 who underwent intramedullary nailing for intertrochanteric femur fractures between November 21, 2013, and November 21, 2023. Two cohorts were analyzed: Cohort A comprised nicotine-dependent patients without tobacco product usage (e.g. cigarettes or chewing tobacco) and Cohort B consisted of patients without any nicotine dependence. Propensity matching was performed for BMI, type 2 diabetes, alcohol/substance abuse, socioeconomic status, and demographic factors. Outcomes assessed included mortality, sepsis, pneumonia, revision, dehiscence, pulmonary embolism, nonunion, and deep vein thrombosis within 1 day to 6 months post-treatment. Results: A total of 2,041 non-tobacco nicotine dependent patients were matched with 22,872 non-nicotine dependent patients. Non-tobacco nicotine dependent patients experienced higher associated risk for numerous postoperative complications compared to non-nicotine dependent patients including increased risk for mortality within 6 months postoperatively (RR 1.386, 10.7% vs 7.7%, P = 0.001), sepsis (RR 1.459, 4.4% vs 3.0%, P = 0.027), and pneumonia (RR 1.751, 5.8% vs 3.3%, P = 0.001). Conclusions: Non-tobacco nicotine dependence increases postoperative complications for patients undergoing intramedullary nailing for intertrochanteric femur fractures. Our findings support the need for development of perioperative nicotine cessation guidelines for non-tobacco nicotine users. Level of evidence: Level III, Prognostic.

Association of Posterior Horn Meniscus Tears with Obesity: A Retrospective Study.

Our study aims to determine the association between obesity and meniscal tears involving the posterior third of the medial meniscus and meniscal root tears. We conducted a 3-year retrospective review of isolated operatively treated meniscal injuries in adult patients performed by a single surgeon. Cases with concomitant pathology were excluded. Patient demographics, height, weight, and body mass index (BMI) were recorded and compared against location of meniscus tear noted via magnetic resonance imaging and arthroscopic imaging. Eighty-nine patients met the inclusion criteria, of which 65.2% were obese (BMI > 30) and 10.1% were morbidly obese (BMI > 40). Average BMI across all patients was 32.6 ± 6.7. Forty-four patients had a tear involving the posterior horn of the medial meniscus, including 20 involving the meniscal root. The average BMI of patients with tears involving the meniscal root was 35.7 ± 6. There was a statistically significant association between type of meniscus tear and BMI as well as height. Obese patients were more likely to have a posterior horn of the medial meniscus tear (odds ratio [OR]: 1.59) and meniscal root tear (OR: 124.67), as were morbidly obese patients (OR: 2.21 and 5.41, respectively). Elevated BMI is associated with posterior horn of the medial meniscus tear. Obesity and morbid obesity are strongly associated with meniscal root tears and tears included in the posterior third of the medial meniscus.

A Population-Based Family Case-Control Study of Sun Exposure and Follicular Lymphoma Risk.

BACKGROUND: Epidemiologic evidence suggests an inverse association between sun exposure and follicular lymphoma risk. METHODS: We conducted an Australian population-based family case-control study based on 666 cases and 459 controls (288 related, 171 unrelated). Participants completed a lifetime residence and work calendar and recalled outdoor hours on weekdays, weekends, and holidays in the warmer and cooler months at ages 10, 20, 30, and 40 years, and clothing types worn in the warmer months. We used a group-based trajectory modeling approach to identify outdoor hour trajectories over time and examined associations with follicular lymphoma risk using logistic regression. RESULTS: We observed an inverse association between follicular lymphoma risk and several measures of high lifetime sun exposure, particularly intermittent exposure (weekends, holidays). Associations included reduced risk with increasing time outdoors on holidays in the warmer months [highest category OR = 0.56; 95% confidence interval (CI), 0.42-0.76; Ptrend < 0.01], high outdoor hours on weekends in the warmer months (highest category OR = 0.71; 95% CI, 0.52-0.96), and increasing time outdoors in the warmer and cooler months combined (highest category OR = 0.66; 95% CI, 0.50-0.91; Ptrend 0.01). Risk was reduced for high outdoor hour maintainers in the warmer months across the decade years (OR = 0.71; 95% CI, 0.53-0.96). CONCLUSIONS: High total and intermittent sun exposure, particularly in the warmer months, may be protective against the development of follicular lymphoma. IMPACT: Although sun exposure is not recommended as a cancer control policy, confirming this association may provide insights regarding the future control of this intractable malignancy.

Clinical, molecular, and cellular immunologic findings in patients with SP110-associated veno-occlusive disease with immunodeficiency syndrome.

BACKGROUND: Mutations in the SP110 gene result in infantile onset of the autosomal recessive primary immunodeficiency disease veno-occlusive disease with immunodeficiency syndrome (VODI), which is characterized by hypogammaglobulinemia, T-cell dysfunction, and a high frequency of hepatic veno-occlusive disease. OBJECTIVES: We sought to further characterize the clinical features, B-lineage cellular immunologic findings, and molecular pathogenesis of this disorder in 9 patients with new diagnoses, including 4 novel mutations from families of Italian, Hispanic, and Arabic ethnic origin. METHODS: Methods used include clinical review; Sanger DNA sequencing of the SP110 gene; determination of transfected mutant protein function by using immunofluorescent studies in Hep-2 cells; quantitation of B-cell subsets by means of flow cytometry; assessments of B-cell function after stimulation with CD40 ligand, IL-21, or both; and differential gene expression array studies of EBV-transformed B cells. RESULTS: We confirm the major diagnostic criteria and the clinical utility of SP110 mutation testing for the diagnosis of VODI. Analysis of 4 new alleles confirms that VODI is caused by reduced functional SP110 protein levels. Detailed B-cell immunophenotyping demonstrated that Sp110 deficiency compromises the ability of human B cells to respond to T cell-dependent stimuli and differentiate into immunoglobulin-secreting cells in vitro. Expression microarray studies have identified pathways involved in B-lymphocyte differentiation and macrophage function. CONCLUSION: These studies show that a range of mutations in SP110 that cause decreased SP110 protein levels and impaired late B-cell differentiation cause VODI and that the condition is not restricted to the Lebanese population.

The delivery of safe and effective test result communication, management and follow-up.

OBJECTIVES: This paper reports on a program of research funded by a National Health and Medical Research Council (NHRMC) partnership grant (2015-2021) entitled "Delivering safe and effective test result communication, management and follow-up". The project's objectives were to: 1) improve the effectiveness and safety of test-result management through the establishment of clear governance processes of communication, responsibility, and accountability; 2) harness health information technology to inform and monitor test-result management; and 3) enhance consumer contribution to the establishment of safe and effective test-result management systems. Type of program: The partnership project addressed its key objectives through: i) the development of a consumer-driven approach; ii) using diagnostic stewardship and digital health to enhance safety and quality; iii) identifying clinical workflows that can lead to timely and meaningful communication; and iv) contributing to the Royal College of Pathologists of Australasia and Australasian Association for Clinical Biochemistry and Laboratory Medicine's work on nationally harmonised alert thresholds for critical laboratory results. METHODS: The project employed a convergent mixed-methods approach using multistage studies across hospitals in South Eastern Sydney and Illawarra and Shoalhaven Local Health Districts. A consumer-centred approach, including patient reference groups and community forums, was used to identify mechanisms to enhance consumers' role in test-management governance processes and inform the direction of the research and interpretation of findings. Results and lessons learnt: The body of evidence generated by the project highlights the multilayered and interconnected components required to achieve safe and effective test results management. Addressing the significant patient safety risk associated with the failure to follow-up test results must include consideration of diagnostic clinical work tasks (involving multiple people across numerous clinical settings) and embrace patient-centred and digital health strategies for shared information and timely and meaningful communication.