Rapid total sialic acid monitoring during cell culture process using a machine learning model based soft sensor.

Total sialic acid content (TSA) in biotherapeutic proteins is often a critical quality attribute as it impacts the drug efficacy. Traditional wet chemical assays to quantify TSA in biotherapeutic proteins during cell culture typically takes several hours or longer due to the complexity of the assay which involves isolation of sialic acid from the protein of interest, followed by sample preparation and chromatographic based separation for analysis. Here, we developed a machine learning model-based technology to rapidly predict TSA during cell culture by using typically measured process parameters. The technology features a user interface, where the users only have to upload cell culture process parameters as input variables and TSA values are instantly displayed on a dashboard platform based on the model predictions. In this study, multiple machine learning algorithms were assessed on our dataset, with the Random Forest model being identified as the most promising model. Feature importance analysis from the Random Forest model revealed that attributes like viable cell density (VCD), glutamate, ammonium, phosphate, and basal medium type are critical for predictions. Notably, while the model demonstrated strong predictability by Day 14 of observation, challenges remain in forecasting TSA values at the edges of the calibration range. This research not only emphasizes the transformative power of machine learning and soft sensors in bioprocessing but also introduces a rapid and efficient tool for sialic acid prediction, signaling significant advancements in bioprocessing. Future endeavors may focus on data augmentation to further enhance model precision and exploration of process control capabilities.

Genetic variants for head size share genes and pathways with cancer.

The size of the human head is highly heritable, but genetic drivers of its variation within the general population remain unmapped. We perform a genome-wide association study on head size (N = 80,890) and identify 67 genetic loci, of which 50 are novel. Neuroimaging studies show that 17 variants affect specific brain areas, but most have widespread effects. Gene set enrichment is observed for various cancers and the p53, Wnt, and ErbB signaling pathways. Genes harboring lead variants are enriched for macrocephaly syndrome genes (37-fold) and high-fidelity cancer genes (9-fold), which is not seen for human height variants. Head size variants are also near genes preferentially expressed in intermediate progenitor cells, neural cells linked to evolutionary brain expansion. Our results indicate that genes regulating early brain and cranial growth incline to neoplasia later in life, irrespective of height. This warrants investigation of clinical implications of the link between head size and cancer.

Risk Factors, Incidence, and Outcomes Associated With Clinically Significant Airway Ischemia.

Airway complications following lung transplantation remain an important cause of morbidity and mortality. We aimed to identify the incidence, risk factors and outcomes associated with clinically significant airway ischemia (CSAI) in our center. We reviewed 217 lung transplants (386 airway anastomoses) performed at our institution between February 2016 and December 2020. Airway images were graded using the 2018 ISHLT grading guidelines modified slightly for retrospective analysis. Airways were considered to have CSAI if they developed ischemia severity >B2, stenosis >50%, and/or any degree of dehiscence within 6-months of transplant. Regression analyses were used to evaluate outcomes and risk factors for CSAI. Eighty-two patients (37.8%) met criteria for CSAI. Of these, twenty-six (32%) developed stenosis and/or dehiscence, and 17 (21%) required interventions. Patients with CSAI had lower one-year (80.5% vs. 91.9%, p = 0.05) and three-year (67.1% vs. 77.8%, p = 0.08) survival than patients without CSAI. Factors associated with CSAI included younger recipient age, recipient diabetes, single running suture technique, performance of the left anastomosis first, lower venous oxygen saturation within 48-h, and takeback for major bleeding. Our single-center analysis suggests that airway ischemia remains a major obstacle in contemporary lung transplantation. Improving the local healing milieu of the airway anastomosis could potentially mitigate this risk.

Causal association of genetically determined caffeine intake from tea or coffee with bone health: a two-sample Mendelian randomization study.

BACKGROUND: Relationship of caffeine intake and consumption of caffeinated beverages, such as tea and coffee, with bone health remains controversial. This study aimed to evaluate whether genetically determined caffeine intake from tea or coffee has causal effects on overall total body bone mineral density (TB-BMD) and fracture. We also assessed the association with TB-BMD in five age strata. METHODS: Using two-sample Mendelian randomization approach, summary statistics were retrieved from genome-wide association studies (GWAS)/GWAS meta-analyses of caffeine intake from tea (n = 395 866)/coffee (n = 373 522), TB-BMD (n = 66 628), and fracture (n = 426 795). Inverse variance weighted method was adopted as the main univariable analysis. Multivariable analysis was conducted to evaluate whether the causal effect is independent. RESULTS: In univariable analysis, genetically determined caffeine intake from tea had positive association with overall TB-BMD (per SD increase in genetically determined caffeine intake, beta of TB-BMD [in SD]: 0.166; 95% confidence interval (CI): 0.006-0.326) and inverse association with fracture (OR = 0.79; 95% CI: 0.654-0.954). Genetically determined caffeine intake from coffee was also positively associated with overall TB-BMD (beta = 0.231; 95% CI: 0.093-0.369). The association remained significant after adjustment for smoking in multivariable analysis. Genetically determined caffeine intake from tea or coffee was both positively associated with TB-BMD in the age strata of 45-60 years, but we lacked evidence of association in other strata. CONCLUSIONS: Genetically, caffeine intake from tea or coffee may be beneficial to bone health. Due to the ascertainment method of caffeine intake from tea, our study also implied genetically higher tea consumption may improve TB-BMD and lower fracture risk.

Prevalence, incidence, and survival analysis of interstitial lung diseases in Hong Kong: a 16-year population-based cohort study.

Background: Published data on the epidemiology of interstitial lung disease (ILD) in Asia is scarce. Understanding the epidemiology is important for authorities in the health management planning. This study aimed to estimate the prevalence, incidence, and survival of ILD in Hong Kong from 2005 to 2020 and evaluate the change of trend over time. Methods: In this retrospective cohort study, we identified ILD patients between 2005 and 2020 using a territory-wide electronic health record database. Prevalence, incidence rates, and age- and sex-standardised incidence rates with United Nations population in 2020 as a reference were estimated. Trends in prevalence and incidence were analysed using joinpoint regression and the average annual percent change (AAPC) was estimated. Median survival, and risk factors of mortality were evaluated using Cox proportional hazard regression. Findings: We identified 5924 patients and included 5884 of them for analysis. The prevalence of ILD increased from 24.7 to 33.6 per 100,000 population from 2005 to 2020 with an AAPC of 1.94 (95% confidence interval, CI: 1.69-2.34). The standardized incidence rate decreased from 5.36 to 2.57 per 100,000 person from 2005 to 2020 (AAPC -3.56, 95% CI, -4.95 to -1.78). The median survival of ILD was 2.50 (95% CI, 2.32-2.69) years. Male, older age, higher Charlson comorbidity index, and IIP subtype were associated with increased mortality with statistical significance. Interpretation: This study provided the first epidemiological evaluation of ILD in Hong Kong. Further studies on ILD in multiple Asian cities and countries are warranted. Funding: None.

Illicit drug use is associated with lower bone mineral density and bone strength.

Objectives: To evaluate the association of illicit drug use with bone mineral density (BMD) and hip geometric parameters at the narrow neck. Methods: This is a cross-sectional matched cohort study conducted in the Hong Kong Chinese population. Associations with illicit drug use were estimated using linear regression for BMD (lumbar spine and femoral neck) and hip geometrical parameters (cross-sectional area [CSA], cross-sectional moment of inertia [CSMI], section modulus [SM], average cortical thickness [ACT] and BMD at the narrow neck) after adjusting for age, body mass index (BMI), smoking status, drinking status, physical activity, and history of antipsychotic and antidepressant use. Mean difference and 95% confidence intervals (95% CI) were calculated between 108 illicit drug users and 108 controls using an adjusted linear model and cluster-robust standard errors after matching by age and sex. The false discovery rate was used to correct for multiple testing. Results: Illicit drug users had a significantly lower BMD (g/cm2) at the lumbar spine (mean difference: -0.062; 95% CI: -0.108 to -0.015), and femoral neck (mean difference: -0.058; 95% CI: -0.106 to -0.010) in the fully adjusted model. Illicit drug users also had a significantly lower CSA (mean difference: -0.238 cm2; 95% CI: -0.462 to -0.013), ACT (mean difference: -0.018 cm; 95% CI: -0.030 to -0.006) and BMD (mean difference: -0.070 g/cm2; 95% CI: -0.128 to -0.012) at the narrow neck. Conclusions: Illicit drug use is associated with lower BMD and bone strength. Future studies evaluating the risk of illicit drug use with fragility fracture are warranted.

Association of Bone Mineral Density and Bone Turnover Markers with the Risk of Diabetes: Hong Kong Osteoporosis Study and Mendelian Randomization.

Preclinical studies demonstrated that bone plays a central role in energy metabolism. However, how bone metabolism is related to the risk of diabetes in humans is unknown. We investigated the association of bone health (bone mineral density [BMD] and bone turnover markers) with incident type-2 diabetes mellitus (T2DM) based on the Hong Kong Osteoporosis Study (HKOS). A total of 993 and 7160 participants from the HKOS were studied for the cross-sectional and prospective analyses, respectively. The cross-sectional study evaluated the association of BMD and bone biomarkers with fasting glucose and glycated hemoglobin (HbA1c ) levels, whereas the prospective study examined the associations between BMD at study sites and the risk of T2DM by following subjects a median of 16.8 years. Body mass index (BMI) was adjusted in all full models. Mendelian randomization (MR) was conducted for causal inference. In the cross-sectional analysis, lower levels of circulating bone turnover markers and higher BMD were significantly associated with increased fasting glucose and HbA1c levels. In the prospective analysis, higher BMD (0.1 g/cm2 ) at the femoral neck and total hip was associated with increased risk of T2DM with hazard ratios (HRs) of 1.10 (95% confidence interval [CI], 1.03 to 1.18) and 1.14 (95% CI, 1.08 to 1.21), respectively. The presence of osteoporosis was associated with a 30% reduction in risk of T2DM compared to those with normal BMD (HR = 0.70; 95% CI, 0.55 to 0.90). The MR results indicate a robust genetic causal association of estimated BMD (eBMD) with 2-h glucose level after an oral glucose challenge test (estimate = 0.043; 95% CI, 0.007 to 0.079) and T2DM (odds ratio = 1.064; 95% CI, 1.036 to 1.093). Higher BMD and lower levels of circulating bone biomarkers were cross-sectionally associated with poor glycemic control. Moreover, higher BMD was associated with a higher risk of incident T2DM and the association is probably causal. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

COVID-19 and cognitive performance: a Mendelian randomization study.

Background: A substantial proportion of individuals with COVID-19 experienced cognitive impairment after resolution of SARS-CoV-2 infection. We aimed to evaluate whether genetic liability to SARS-CoV-2 infection per se, or more severe COVID-19, is causally linked to cognitive deficit. Methods: We firstly performed univariable Mendelian randomization (MR) analysis to examine whether genetic liability to SARS-CoV-2 infection, hospitalized and severe COVID-19 is causally associated with cognitive performance. To dissect the causal pathway, multivariable MR (MVMR) analysis was conducted by adjusting for five inflammatory markers [C-reactive protein, interleukin (IL)-1ß, IL-6, IL-8, and tumour necrosis factor α, as proxies of systemic inflammation]. Results: In univariable MR analysis, host genetic liability to SARS-CoV-2 infection was associated with lower cognitive performance [inverse variance weighted (IVW) analysis, estimate: -0.023; 95% Confidence Interval (CI): -0.038 to -0.009]. Such causal association was attenuated in MVMR analysis when we adjusted for the five correlated inflammatory markers in one analysis (IVW analysis, estimate: -0.022; 95% CI: -0.049 to 0.004). There was insufficient evidence of association for genetic liability to hospitalized and severe COVID-19 with cognitive performance. Conclusion: The causal effect of host genetic liability to SARS-CoV-2 infection on reduced cognitive performance may be mediated by systemic inflammation. Future studies examining whether anti-inflammatory agents could alleviate cognitive impairment in SARS-CoV-2-infected individuals are warranted.

Burnout Syndrome in Lung Transplant Physicians.

Objective: Burnout syndrome is common in physicians, but little is known about burnout in lung transplant physicians specifically. The purpose of this study was to explore burnout and its relationship to job factors and depression in lung transplant physicians.Design: A cross-sectional study that included lung transplant pulmonologists and surgeons was performed via electronic survey.Setting: The lung transplant physicians surveyed practiced worldwide.Methods: The survey incorporated questions about demographics and job characteristics as well as the Maslach Burnout Inventory and Patient Health Questionnaire-2. Burnout was defined by high emotional exhaustion or depersonalization.Participants: Ninety physicians worldwide completed the survey.Results: Of the 90 physicians who completed the entire survey, 44 (48.9%) had burnout with 38 (42.2%) having high emotional exhaustion, 15 (16.7%) having high depersonalization, and 9 (10.0%) with both. Of the respondents, 14 (15.6%) had high risk of depression, and of these, 13 also had high emotional exhaustion. There was a positive correlation between depression score and emotional exhaustion score (P=0.67, P<0.001). Depression was more common in surgeons compared with pulmonologists (35.7% versus 11.8%, P=0.02). There was a trend toward more burnout by emotional exhaustion in physicians with more versus less work experience (68.4% versus 31.6%, P=0.056).Conclusions: Emotional exhaustion is common in lung transplant physicians and is associated with depression and a negative impact on life.

Safety and utility of indwelling pleural catheters in lung transplant recipients.

INTRODUCTION: The safety and efficacy of indwelling pleural catheters (IPCs) in lung allograft recipients is under-reported. METHODS: We performed a multicenter, retrospective analysis between 1/1/2010 and 6/1/2022 of consecutive IPCs placed in lung transplant recipients. Outcomes included incidence of infectious and non-infectious complications and rate of auto-pleurodesis. RESULTS: Seventy-one IPCs placed in 61 lung transplant patients at eight centers were included. The most common indication for IPC placement was recurrent post-operative effusion. IPCs were placed at a median of 59 days (IQR 40-203) post-transplant and remained for 43 days (IQR 25-88). There was a total of eight (11%) complications. Infection occurred in five patients (7%); four had empyema and one had a catheter tract infection. IPCs did not cause death or critical illness in our cohort. Auto-pleurodesis leading to the removal of the IPC occurred in 63 (89%) instances. None of the patients in this cohort required subsequent surgical decortication. CONCLUSIONS: The use of IPCs in lung transplant patients was associated with an infectious complication rate comparable to other populations previously studied. A high rate of auto-pleurodesis was observed. This work suggests that IPCs may be considered for the management of recurrent pleural effusions in lung allograft recipients.

Development and validation of the Chinese osteoporosis screening algorithm (COSA) in identification of people with high risk of osteoporosis.

Objectives: To enhance the public awareness and facilitate diagnosis of osteoporosis, we aim to develop a new Chinese Osteoporosis Screening Algorithm (COSA) to identify people at high risk of osteoporosis. Methods: A total of 4747 postmenopausal women and men aged ≥ 50 from the Hong Kong Osteoporosis Study were randomly split into a development (N = 2373) and an internal validation cohort (N = 2374). An external validation cohort comprising 1876 community-dwelling subjects was used to evaluate the positive predictive value (PPV). Results: Among 11 predictors included, age, sex, weight, and history of fracture were significantly associated with osteoporosis after correction for multiple testing. Age- and sex-stratified models were developed due to the presence of significant sex and age interactions. The area under the curve of the COSA in the internal validation cohort was 0.761 (95% CI, 0.711-0.811), 0.822 (95% CI, 0.792-0.851), and 0.946 (95% CI, 0.908-0.984) for women aged < 65, women aged ≥ 65, and men, respectively. The COSA demonstrated improved reclassification performance when compared to Osteoporosis Self-Assessment Tool for Asians. In the external validation cohort, the PPV of COSA was 40.6%, 59.4%, and 19.4% for women aged < 65, women aged ≥ 65, and men, respectively. In addition, COSA > 0 was associated with an increased 10-year risk of hip fracture in women ≥ 65 (OR, 4.65; 95% CI, 2.24-9.65) and men (OR, 11.51; 95% CI, 4.16-31.81). Conclusions: We have developed and validated a new osteoporosis screening algorithm, COSA, specific for Hong Kong Chinese.

Development and validation of sex-specific hip fracture prediction models using electronic health records: a retrospective, population-based cohort study.

Background: Hip fracture is associated with immobility, morbidity, mortality, and high medical cost. Due to limited availability of dual-energy X-ray absorptiometry (DXA), hip fracture prediction models without using bone mineral density (BMD) data are essential. We aimed to develop and validate 10-year sex-specific hip fracture prediction models using electronic health records (EHR) without BMD. Methods: In this retrospective, population-based cohort study, anonymized medical records were retrieved from the Clinical Data Analysis and Reporting System for public healthcare service users in Hong Kong aged ≥60 years as of 31 December 2005. A total of 161,051 individuals (91,926 female; 69,125 male) with complete follow-up from 1 January 2006 till the study end date on 31 December 2015 were included in the derivation cohort. The sex-stratified derivation cohort was randomly divided into 80% training and 20% internal testing datasets. An independent validation cohort comprised 3046 community-dwelling participants aged ≥60 years as of 31 December 2005 from the Hong Kong Osteoporosis Study, a prospective cohort which recruited participants between 1995 and 2010. With 395 potential predictors (age, diagnosis, and drug prescription records from EHR), 10-year sex-specific hip fracture prediction models were developed using stepwise selection by logistic regression (LR) and four machine learning (ML) algorithms (gradient boosting machine, random forest, eXtreme gradient boosting, and single-layer neural networks) in the training cohort. Model performance was evaluated in both internal and independent validation cohorts. Findings: In female, the LR model had the highest AUC (0.815; 95% Confidence Interval [CI]: 0.805-0.825) and adequate calibration in internal validation. Reclassification metrics showed the LR model had better discrimination and classification performance than the ML algorithms. Similar performance was attained by the LR model in independent validation, with high AUC (0.841; 95% CI: 0.807-0.87) comparable to other ML algorithms. In internal validation for male, LR model had high AUC (0.818; 95% CI: 0.801-0.834) and it outperformed all ML models as indicated by reclassification metrics, with adequate calibration. In independent validation, the LR model had high AUC (0.898; 95% CI: 0.857-0.939) comparable to ML algorithms. Reclassification metrics demonstrated that LR model had the best discrimination performance. Interpretation: Even without using BMD data, the 10-year hip fracture prediction models developed by conventional LR had better discrimination performance than the models developed by ML algorithms. Upon further validation in independent cohorts, the LR models could be integrated into the routine clinical workflow, aiding the identification of people at high risk for DXA scan. Funding: Health and Medical Research Fund, Health Bureau, Hong Kong SAR Government (reference: 17181381).

Transcriptome-wide summary data-based Mendelian randomization analysis reveals 38 novel genes associated with severe COVID-19.

Severe COVID-19 has a poor prognosis, while the genetic mechanism underlying severe COVID-19 remains largely unknown. We aimed to identify genes that are potentially causally associated with severe COVID-19. We conducted a summary data-based Mendelian randomization (SMR) analysis using expression quantitative trait loci (eQTL) data from 49 different tissues as the exposure and three COVID-19-phenotypes (very severe respiratory confirmed COVID-19 [severe COVID-19], hospitalized COVID-19, and SARS-CoV-2 infection) as the outcomes. SMR using multiple SNPs was used as a sensitivity analysis to reduce false positive rate. Multiple testing was corrected using the false discovery rate (FDR) q-value. We identified 309 significant gene-trait associations (FDR q value < 0.05) across 46 tissues for severe COVID-19, which mapped to 64 genes, of which 38 are novel. The top five most associated protein-coding genes were Interferon Alpha and Beta Receptor Subunit 2 (IFNAR2), 2'-5'-Oligoadenylate Synthetase 3 (OAS3), mucin 1 (MUC1), Interleukin 10 Receptor Subunit Beta (IL10RB), and Napsin A Aspartic Peptidase (NAPSA). The potential causal genes were enriched in biological processes related to type I interferons, interferon-gamma inducible protein 10 production, and chemokine (C-X-C motif) ligand 2 production. In addition, we further identified 23 genes and 5 biological processes which are unique to hospitalized COVID-19, as well as 13 genes that are unique to SARS-CoV-2 infection. We identified several genes that are potentially causally associated with severe COVID-19. These findings improve our limited understanding of the mechanism of COVID-19 and shed light on the development of therapeutic agents for treating severe COVID-19.

Association of maternal levothyroxine use during pregnancy with offspring birth and neurodevelopmental outcomes: a population-based cohort study.

BACKGROUND: The influence of maternal levothyroxine treatment during pregnancy remains unclear. This study aimed to evaluate the associations of maternal levothyroxine treatment during pregnancy with the birth and neurodevelopmental outcomes in offspring. METHODS: This population-based cohort study was conducted among pregnant women using the Hong Kong Clinical Data Analysis and Reporting System. Mother-child pairs in Hong Kong from 2001 to 2015 were included and children were followed up till 2020. We defined the exposure group as mothers who were exposed to levothyroxine during pregnancy. Preterm birth and small for gestational age (SGA) were included as birth outcomes. Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) were included as neurodevelopmental outcomes. Odds ratios (OR) or hazard ratios (HRs) with a 95% confidence interval (CI) were evaluated to assess the association of gestational levothyroxine use with offspring birth and neurodevelopmental outcomes respectively, using propensity score fine-stratification weighting and a Cox proportional hazards regression model. RESULTS: Among 422,156 mother-child pairs, 2125 children were born from mothers exposed to levothyroxine during pregnancy. A significantly increased risk of preterm birth was observed in children with maternal levothyroxine exposure during pregnancy, when compared to mothers who had no history of thyroid-related diagnoses or prescriptions (weighted OR [wOR]: 1.22, 95% CI: 1.07, 1.39). Similarly, an increased risk of preterm birth was found among children of gestational levothyroxine users, when compared to children of mothers who had used levothyroxine before but stopped during pregnancy (wOR: 2.16, 95% CI: 1.09, 4.25). Sensitivity analysis, by excluding mothers exposed to psychotropic or antiepileptic medications before or during pregnancy, also indicated a similar increased risk of preterm birth regarding the gestational use of levothyroxine (wOR: 1.26, 95% CI: 1.10, 1.45). No significant association was observed for the risk of SGA, ADHD, and ASD. CONCLUSIONS: There is no evidence that gestational use of levothyroxine is associated with SGA, ADHD, or ASD in offspring. Gestational levothyroxine treatment is associated with a higher risk of preterm birth. Such risk might be confounded by the underlying maternal thyroid disease itself, however, we cannot completely exclude the possible effect of gestational L-T4 treatment on offspring preterm birth. Our findings provided support to the current guidelines on the cautious use of levothyroxine treatment during pregnancy.

Unravelling genetic causality of haematopoiesis on bone metabolism in human.

Objective: Haematopoiesis was shown to regulate bone metabolism in in vivo studies. However, whether haematopoiesis has causal effects on bone health has never been investigated in humans. We aimed to evaluate the causal relationships of blood traits with bone mineral density (BMD) and fracture. Design and methods: Using two-sample Mendelian randomization, causal relationship of 29 blood traits with estimated BMD (eBMD), total body BMD (TBBMD), lumbar spine BMD (LSBMD), femoral neck BMD (FNBMD) and fracture were evaluated by inverse-variance weighted (IVW) method and multiple sensitivity analyses. Relevant genetic data were obtained from the largest possible publicly available genome-wide association studies. Results: Eight genetically determined red blood cell traits showed positive causal effects on eBMD, with beta estimates ranging from 0.009 (mean corpuscular haemoglobin) to 0.057 (haemoglobin concentration), while three white blood cell traits, including lymphocyte count (beta: -0.020; 95% CI: -0.033 to -0.007), neutrophil count (beta: -0.020; 95% CI: -0.035 to -0.006) and white blood cell count (beta: -0.027; 95% CI: -0.039 to -0.014), were inversely associated with eBMD. Causal effects for six of these blood traits were validated on TBBMD, LSBMD, FNBMD and/or fracture. The association of reticulocyte count (beta: 0.040; 95% CI: 0.016 to 0.063), haemoglobin (beta: 0.058; 95% CI: 0.021 to 0.094) and mean corpuscular haemoglobin concentration (beta: 0.030; 95% CI: 0.007 to 0.054) with eBMD remained significant in multivariable IVW analyses adjusted for other blood traits. Conclusion: This study provided evidence that haematopoietic system might regulate the skeletal system in humans and suggested the possible pathophysiology of bone diseases among people with haematological diseases. Significance statement: We conducted a novel Mendelian randomization study investigating the causal relationship of blood cells with bone mineral density. Red and white blood cell traits have positive and inverse causal relationship with bone mineral density, respectively, suggesting a potential link of haematopoietic system with the skeletal system in humans. Current findings suggest individuals with related haematological diseases, such as anaemia and leukocytosis, may have a lifelong increased risk of osteoporosis and/or fracture. Given that complete blood count is commonly performed in clinical setting, whether complete blood count can be used to predict fracture risk warrants further investigation.

Low Bone Mineral Density With Risk of Dementia: A Prospective Cohort Study.

OBJECTIVES: Osteoporosis and dementia often coexist, but the association between the 2 diseases remains unclear. This study aimed to investigate the relationship between bone mineral density (BMD) and the risk of incident dementia. DESIGN: Prospective cohort study, the Hong Kong Osteoporosis Study (HKOS). SETTING AND PARTICIPANTS: Data were from the HKOS and the Clinical Data Analysis and Reporting System (CDARS) in Hong Kong. A total of 5803 participants aged ≥40 years and free of dementia were included in the HKOS. METHODS: The baseline BMD at the lumbar spine, femoral neck, trochanter, and total hip were measured using dual-energy x-ray absorptiometry (DXA). The incidence of dementia was identified using their International Classification of Diseases, Ninth Revision, codes. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% CIs. RESULTS: The median follow-up time of the HKOS was 16.8 years. Higher BMD T scores at the lumbar spine, trochanter, and total hip were significantly associated with the reduced risk of dementia with the respective HR of 0.85 (95% CI 0.76-0.95; P = .004), 0.78 (95% CI 0.68-0.90; P < .001), and 0.82 (95% CI 0.72-0.93; P = .003). The subgroup analyses showed that associations were significant in women but not in men, whereas the associations were unaltered after adjusting for serum estradiol. CONCLUSIONS AND IMPLICATIONS: Low BMD was associated with an increased risk of dementia, particularly in women. Future studies evaluating the clinical usefulness of BMD on dementia prediction and management are warranted.

Hip Fracture as a Predictive Marker for the Risk of Dementia: A Population-Based Cohort Study.

OBJECTIVES: This study aimed to investigate the association between hip fracture and the risk of dementia. DESIGN: A retrospective real-world propensity score-matched cohort study was conducted using the real-world hip fracture cohort (RHFC). SETTING AND PARTICIPANTS: Electronic health record data from the Clinical Data Analysis and Reporting System (CDARS) in Hong Kong were used. A total of 52,848 patients aged ≥65 years and with at least an event of fall from 2006 to 2015 were included in the RHFC. METHODS: The incidence of fall, hip fracture, and dementia was determined using their International Classification of Diseases, Ninth Revision (ICD-9) codes. Competing risk regression models were used to estimate hazard ratios (HRs) and 95% CIs. RESULTS: Hip fracture was associated with an increased risk of dementia (HR 1.09, 95% CI 1.04-1.15, P < .001). The subgroup analysis showed that association was significant in women but not in men. CONCLUSIONS AND IMPLICATIONS: Hip fracture was associated with the increased risk of dementia among older adults. Further studies investigating the potential roles of hip fracture in the development of dementia could benefit the management of both conditions in older adults.

Pediatric lung transplantation for COVID-19: Unique clinical and psychosocial barriers.

BACKGROUND: SARS-CoV-2 infection in the age group of 0-17 years contributes to approximately 22% of all laboratory-confirmed SARS-CoV-2 infections. Fortunately, this age group has a lower death rate (0.5 per 100 000) that accounts for only 4% of the total deaths due to COVID-19. Despite the low mortality rate in the pediatric population, children of minority groups represented 78% of the deaths highlighting the existing disparities in access to health care. METHODS: With the emergence of the more contagious COVID-19 variants and the relatively slow pace of vaccination among the pediatric population, it is possible to see more cases of significant lung injury and potential for transplantation for the younger age group. RESULTS: To our knowledge, our patient is the youngest to have undergone lung transplantation for SARS-CoV-2. CONCLUSION: The case presented unique challenges, particularly in relation to timing for listing and psychosocial support for parents who were his decision makers.

COVID-19 and platelet traits: A bidirectional Mendelian randomization study.

This study aimed to evaluate the host genetic liability of coronavirus disease 2019 (covid-19) with platelet traits using the Mendelian randomization (MR) approach. We conducted a bidirectional two-sample MR using summary statistics from the largest genome-wide association study of three variables, covid-19 severity (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] infection, covid-19 hospitalization, and severe covid-19, N = ~1 059 456-1 557 411) and four platelet traits (mean platelet volume [MPV], plateletcrit, platelet distribution width, and platelet count; N = 408 112). Inverse-variance weighted (IVW), median weighted, MR-Egger, and contamination mixture methods were used to estimate the causal association. Null and inconsistent associations in the IVW and sensitivity analyses were observed for SARS-CoV-2 infection and covid-19 hospitalization with platelet traits. For severe covid-19, significant associations with MPV and platelet count were observed in the IVW and sensitivity analyses, with the betaIVW of 0.01 (95% confidence interval [CI]: 0.005-0.016, p = 3.51 × 10-4 ) and -0.009 (95% CI: -0.015 to -0.002, p = 0.008) per doubling in odds of severe covid-19, respectively. Conversely, null associations were observed for platelet traits with covid-19 traits. In conclusion, host genetic liability to severe covid-19 was causally associated with increased MPV and reduced platelet count, which may provide insights into evaluating hypercoagulability and thromboembolic events in covid-19 patients.