The hindbrain and cortico-reticular pathway in adolescent idiopathic scoliosis.

AIM: To characterise the corticoreticular pathway (CRP) in a case-control cohort of adolescent idiopathic scoliosis (AIS) patients using high-resolution slice-accelerated readout-segmented echo-planar diffusion tensor imaging (DTI) to enhance the discrimination of small brainstem nuclei in comparison to automated whole-brain volumetry and tractography and their clinical correlates. MATERIALS AND METHODS: Thirty-four participants (16 AIS patients, 18 healthy controls) underwent clinical and orthopaedic assessments and brain magnetic resonance imaging (MRI) on a 3 T MRI machine. Automated whole-brain volume-based morphometry, tract-based spatial statistics analysis, and manual CRP tractography by two independent raters were performed. Intra-rater and inter-rater agreement of DTI metrics from CRP tractography were assessed by intraclass correlation coefficient. Normalised structural brain volumes and DTI metrics were compared between groups using Student's t-tests. Linear correlation analysis between imaging parameters and clinical scores was also performed. RESULTS: AIS patients demonstrated a significantly larger pons volume compared to controls (p=0.006). Significant inter-side CRP differences in mean (p=0.02) and axial diffusivity (p=0.01) were found in patients only. Asymmetry in CRP fractional anisotropy significantly correlated with the Cobb angle (p=0.03). CONCLUSION: Relative pontine hypertrophy and asymmetry in CRP DTI metrics suggest central supranuclear inter-hemispheric imbalance in AIS, and support the role of the CRP in axial muscle tone. Longitudinal evaluation of CRP DTI metrics in the prediction of AIS progression may be clinically relevant.

An interpretable knee replacement risk assessment system for osteoarthritis patients.

Objective: Knee osteoarthritis (OA) is a complex disease with heterogeneous representations. Although it is modifiable to prevention and early treatment, there still lacks a reliable and accurate prognostic tool. Hence, we aim to develop a quantitative and self-administrable knee replacement (KR) risk stratification system for knee osteoarthritis (KOA) patients with clinical features. Method: A total of 14 baseline features were extracted from 9592 cases in the Osteoarthritis Initiative (OAI) cohort. A survival model was constructed using the Random Survival Forests algorithm. The prediction performance was evaluated with the concordance index (C-index) and average receiver operating characteristic curve (AUC). A three-class KR risk stratification system was built to differentiate three distinct KR-free survival groups. Thereafter, Shapley Additive Explanations (SHAP) was introduced for model explanation. Results: KR incidence was accurately predicted by the model with a C-index of 0.770 (±0.0215) and an average AUC of 0.807 (±0.0181) with 14 clinical features. Three distinct survival groups were observed from the ten-point KR risk stratification system with a four-year KR rate of 0.79%, 5.78%, and 16.2% from the low, medium, and high-risk groups respectively. KR is mainly caused by pain medication use, age, surgery history, diabetes, and a high body mass index, as revealed by SHAP. Conclusion: A self-administrable and interpretable KR survival model was developed, underscoring a KR risk scoring system to stratify KOA patients. It will encourage regular self-assessments within the community and facilitate personalised healthcare for both primary and secondary prevention of KOA.

Risks and impacts of thromboembolism in patients with pancreatic cancer.

INTRODUCTION: Patients with pancreatic cancer have a high risk of thromboembolism (TE), which may increase mortality. Most relevant studies have been conducted in Western populations. We investigated risk factors for TE in a predominantly Chinese population of patients with pancreatic cancer, along with effects of TE on overall survival. METHODS: This retrospective cohort study included patients diagnosed with exocrine pancreatic cancer in Prince of Wales Hospital in Hong Kong between 2010 and 2015. Data regarding patient demographics, World Health Organization performance status, stage, treatment, TE-related information, and time of death (if applicable) were retrieved from electronic medical records. Univariate and multivariable logistic regression analyses were performed to identify risk factors for TE. Survival analyses were performed using Kaplan-Meier analysis and Cox proportional hazards regression. RESULTS: In total, 365 patients were included in the study. The overall incidence of TE (14.8%) was lower than in Western populations. In univariate logistic regression analysis, stage IV disease and non-head pancreatic cancer were significantly associated with TE (both P=0.01). Multivariable logistic regression analysis showed that stage IV disease was a significant risk factor (odds ratio=1.08, 95% confidence interval [CI]=1.00-1.17; P=0.046). Median overall survival did not significantly differ between patients with and without TE (4.88 months vs 7.80 months, hazard ratio=1.08, 95% CI=0.80-1.49; P=0.58) and between patients with TE who received anticoagulation treatment or not (5.63 months vs 4.77 months, hazard ratio=0.72, 95% CI=0.40-1.29; P=0.27). CONCLUSION: The incidence of TE was low in our Chinese cohort. Stage IV disease increased the risk of TE. Overall survival was not affected by TE or its treatment.

Oestradiol concentrations in trans women with HIV suppressed on unboosted integrase inhibitor regimens versus trans women without HIV taking oral oestradiol: a pilot study.

BACKGROUND: Feminizing hormone therapy (FHT) is essential to many trans women. Concern about negative drug interactions between FHT and ART can be an ART adherence barrier among trans women with HIV. OBJECTIVES: In this single-centre, parallel group, cross-sectional pilot study, we measured serum oestradiol concentrations in trans women with HIV taking FHT and unboosted integrase strand transfer inhibitor (INSTI)-based ART versus trans women without HIV taking FHT. METHODS: We included trans women with and without HIV, aged ≥18 years, taking ≥2 mg/day of oral oestradiol for at least 3 months plus an anti-androgen. Trans women with HIV were on suppressive ART ≥3 months. Serum oestradiol concentrations were measured prior to medication dosing and 2, 4, 6 and 8 h post-dose. Median oestradiol concentrations were compared between groups using Wilcoxon rank-sum tests. RESULTS: Participants (n = 8 with HIV, n = 7 without) had a median age of 32 (IQR: 28, 39) years. Among participants, the median oral oestradiol dose was 4 mg (range 2-6 mg). Participants had been taking FHT for a median of 4 years (IQR: 2, 8). Six trans women with HIV were taking bictegravir/emtricitabine/tenofovir alafenamide and two were taking dolutegravir/abacavir/lamivudine. All oestradiol concentrations were not significantly different between groups. Eleven (73%) participants had target oestradiol concentrations in the range 200-735 pmol/L at C4h (75% among women with HIV, 71% among those without HIV). CONCLUSIONS: Oestradiol concentrations were not statistically different in trans women with HIV compared with those without HIV, suggesting a low probability of clinically relevant drug-drug interactions between FHT and unboosted INSTI-based ART.

Effects of primary granulocyte-colony stimulating factor prophylaxis on neutropenic toxicity and chemotherapy dose delivery in Chinese patients with breast cancer who received adjuvant docetaxel plus cyclophosphamide chemotherapy: a retrospective cohort study.

INTRODUCTION: This study was performed to examine the effects of primary granulocyte-colony stimulating factor (G-CSF) prophylaxis on neutropenic toxicity, chemotherapy delivery, and hospitalisation among Chinese patients with breast cancer in Hong Kong. METHODS: This retrospective study included patients with breast cancer who received adjuvant docetaxel plus cyclophosphamide chemotherapy from November 2007 to October 2013 at Princess Margaret Hospital. Data were collected regarding the usage of G-CSF prophylaxis; incidences of grade 3 or 4 neutropenia, febrile neutropenia, non-neutropenic fever, and infection; hospital admissions, and chemotherapy dose delivery. Patients who began to receive G-CSF prophylaxis during the first cycle of chemotherapy and continued such prophylaxis in subsequent cycles were regarded as the primary G-CSF prophylaxis group. RESULTS: In total, 231 female Chinese patients with breast cancer were included in the analysis. Overall, 193 (83.5%) patients received primary G-CSF prophylaxis. The demographics and tumour characteristics were comparable between patients with and without primary G-CSF prophylaxis. Primary G-CSF prophylaxis significantly reduced febrile neutropenia incidence from 31.6% to 14.5% (relative risk=0.45, 95% confidence interval=0.25-0.81). Primary G-CSF prophylaxis also significantly reduced the incidence of grade 3 or 4 neutropenia from 57.9% to 24.7% (relative risk=0.43, 95% confidence interval=0.30-0.62) and the incidence of febrile neutropenia-related hospital admission from 31.6% to 12.4% (P=0.025). Finally, it enabled more patients to receive adequate chemotherapy dose delivery. CONCLUSION: Primary G-CSF prophylaxis effectively reduced the incidences of grade 3 or 4 neutropenia and febrile neutropenia, while enabling adequate chemotherapy dose delivery and reducing hospital admissions among Chinese patients with breast cancer who received adjuvant docetaxel plus cyclophosphamide chemotherapy.

Prevalence and Correlates of Caregiver Anxiety in Family Caregivers of Patients With Advanced Cancer: a Cross-Sectional Study in a Palliative Care Unit in Hong Kong.

OBJECTIVES: To assess the prevalence of caregiver anxiety and to identify correlates of caregiver anxiety in family caregivers of patients with advanced cancer in a palliative care unit in Hong Kong. METHODS: Family caregivers of patients admitted to the palliative care ward for the first time between July 2019 and September 2019 were screened for recruitment. Caregiver demographics (age, sex, marital status, occupation, education level, housing condition, relationship with the patient, known diagnosis of anxiety or depression, and Charlson comorbidity index) were collected, as were caregiver understanding of patient's diagnosis and prognosis, perceived patient's distress, frequency of witnessing confusion or delirium of patients in past month, perceived adequacy of psychological support (other than general social support), and perceived anxiety towards patient's approaching death. Caregiver anxiety was assessed using the 7-item Generalised Anxiety Disorder scale (GAD-7). Caregiver depression status was assessed using the 9-item Patient Health Questionnaire (PHQ-9). Caregiver psychological well-being was assessed using the 11-item Psychological Well-being Scale for Family Caregivers (PWS-C). Caregiver overall burden was assessed using the Chinese version of the 13-item Modified Caregiver Strain Index (C-M-CSI). RESULTS: 70 caregivers (of 66 patients) were included, with a response rate of 98.6%. 16 (22.9%) caregivers had moderate to severe anxiety (GAD-7 score of ≥10). The GAD-7 score was higher in female caregivers than in male caregivers (mean rank: 39.26 vs 27.83, p = 0.026). 26 (37.1%) caregivers had depression (PHQ-9 score of ≥7). The GAD-7 score of caregivers was associated with the PHQ-9 score (rs = 0.834, p < 0.01), the four subscales of PWS-C: social support (rs = -0.308, p = 0.01), life meaning (rs = -3.30, p < 0.01), emotional distress (rs = 0.615, p < 0.01), and caregiver inadequacy (rs = 0.41, p < 0.01), and the C-M-CSI score for caregiver overall burden (rs = 0.332, p < 0.01). In multiple linear regression, predictors for GAD-7 score were the PHQ-9 score, caregiver's feeling of anxiety towards patient's approaching death, and caregiver sex. CONCLUSIONS: 22.9% of family caregivers of patients with advanced cancer have moderate to severe anxiety. Anxiety of caregivers was associated with depression, caregiver's feeling of anxiety towards patient's approaching death, psychological support, and life meaning. All these are potentially amendable by interventions. A structured screening of anxiety in family caregivers of patients with advanced cancer should be considered as routine practice.

Short report: Characterizing HIV care among a clinical sample of transgender women living with HIV.

INTRODUCTION: This study aimed to characterize and identify factors associated with HIV care among transgender (trans) women living with HIV (TWLWH) in two urban centres in Canada. METHODS: Retrospective data were collected from clinic charts of TWLWH aged 16 years and older across seven family medicine, endocrinology and/or HIV clinics in Montreal and Toronto, Canada, from 2018 to 2019 (n = 86). We assessed the proportion of individuals being ever engaged in HIV care [defined as having any recorded antiretroviral therapy (ART) regimen and/or viral load], current ART use, and most recent viral load (suppressed [<200 copies/ml] vs. unsuppressed) overall and compared across subgroups using χ2 tests. RESULTS: All TWLWH in our sample [100.0%, 95% confidence interval (CI): 95.8-100.0%] were engaged in HIV care; most (93.0%, 95% CI: 85.4-97.4%) were currently using ART and most (93.4%, 95% CI: 85.3-97.8%) with complete data (n = 71/76) were virally suppressed. A higher proportion of trans women of colour (100.0%) reported current ART use compared with white trans women (76.9%, p = 0.017). A higher proportion of those with no documented history of injection drug use (IDU; 96.6%) were virally suppressed compared with those with a history of IDU (66.7%, p = 0.022). Although not statistically significant, 96.2% of those currently reporting feminizing hormone use were virally suppressed, compared with 85.0% of those not reporting use (p = 0.202). CONCLUSIONS: Once engaged in HIV care, TWLWH in Canada appear to have excellent ART use and viral suppression. Findings can be leveraged to identify target populations to enhance HIV care and to further explore the relationship between gender-affirming medical care and HIV care.

Assessing the Impact of a Patient Navigator Intervention Program for Vietnamese-American Women with Abnormal Mammograms.

Breast cancer incidence among Asian Americans increased at a rate of 1.8% per year from 2014 to 2018, while the general population's incidence rate remained stable. Vietnamese-American women have been found to have the longest follow-up time after an abnormal mammogram. This study assesses the impact of a patient navigator program for Vietnamese-American women who received abnormal mammograms. Ninety-six Vietnamese-American participants with abnormal mammograms were assigned a Vietnamese patient navigator to provide emotional support, education, translation, and assistance with medical bills and doctor's appointments. Data collected from pre-test, post-test (1 year after initial enrollment in program), and 3-month follow-up surveys measured psychosocial outcomes and participant satisfaction. All 96 participants attended follow-up appointments for their abnormal mammograms. Psychosocial outcomes worsened from pre- to post-test, though these results were not statistically significant. Feeling in control of situations in one's life improved and was significant for participants who did not receive a breast cancer diagnosis (4.31, 5.04, p = .039). A majority of the participants reported satisfaction with their patient navigators. Vietnamese-American women have been found to be the least adherent to appropriate follow-up after an abnormal mammogram; in this study, all 96 participants attended a follow-up appointment within 90 days. Findings did not show improvements in psychosocial outcomes. Past research suggests that sociocultural factors may be at play: the initial abnormal mammogram may have triggered fatalistic thoughts affecting the reactions of the participants, even though the abnormal mammogram did not result in a breast cancer diagnosis.

Burnout and well-being in young doctors in Hong Kong: a territory-wide cross-sectional survey.

INTRODUCTION: This territory-wide study evaluated the level of burnout and health status among young doctors in Hong Kong. METHODS: All young doctors in Hong Kong, defined as residents-in-training or doctors within 10 years of their specialist registration, were invited to participate in an online cross-sectional survey. This survey used standardised questionnaires including the Copenhagen Burnout Inventory (CBI) for burnout, Patient Health Questionnaire-9 for depression, and general health questionnaires. RESULTS: In total, 514 doctors completed the survey; 284 were doctors within 10 years of their specialist registration, while 230 were residents-in-training. There were 277 women (54%); among all respondents, the mean age was 33.7 ± 6.1 years. Using a CBI subscale cut-off score of ≥50 (moderate and higher), 72.6% (n=373) of respondents reported personal burnout; 70.6% (n=363) of respondents reported work-related burnout; and 55.4% (n=285) of respondents reported client-related burnout. Furthermore, 24% (n=125) of respondents were "somewhat dissatisfied" with their present job position; 4% (n=19) of respondents were "very dissatisfied" with their present job position. The prevalence of depression among respondents was 21% (n=110). CONCLUSIONS: In this territory-wide cross-sectional survey of young doctors in Hong Kong, a high prevalence of burnout was identified among young doctors; respondents exhibited a considerable level of depression and substantial dissatisfaction with their current positions. Strategies to address these problems must be formulated to ensure the future well-being of the medical and dental workforce in Hong Kong.

Analysis of complications following multidisciplinary functional intervention in paediatric craniomaxillofacial deformities.

Paediatric craniomaxillofacial (CMF) surgery requires a multidisciplinary team approach to ensure the optimal and holistic management of children with craniofacial deformities. The aim of this retrospective study was to analyse the complications following functional interventions among 34 CMF deformity patients in a single multidisciplinary craniofacial centre. Electronic data including patient demographic characteristics and clinical entry were analysed. Inclusion criteria were all paediatric patients with CMF deformities who underwent various functional interventions. A total of 64 interventions (48 intermediate and 16 definitive) were conducted. Based on the Sharma classification of complications, 20.3% were type I, 4.7% were type II, 1.6% were type III, and 4.7% were type IV . Most complications were type I, which included local infection (3.1%) and premature opening of tarsorrhaphy (3.1%). More serious complications (types III and IV) included temporary visual loss (1.6%) and intraoperative haemorrhage (1.6%). Although a low complication rate was observed in intermediate interventions, a higher complication rate was observed in more complex definitive interventions such as monobloc distraction osteogenesis. Although most complications were manageable, effective prevention remains mandatory, as serious complications may lead to permanent damage and mortality. This analysis highlights the importance of a multidisciplinary team approach to optimize the outcomes in CMF patient management.

A machine learning-based approach to decipher multi-etiology of knee osteoarthritis onset and deterioration.

Objectives: By deploying a novel combination of machine learning approaches, we aim to investigate the contributions of each local and systemic risk factors in multi-etiology of knee osteoarthritis (KOA) to disease onset and deterioration. Methods: A machine-learning-based KOA progression prediction model is developed using the data from the National Institute of Health Osteoarthritis Biomarkers Consortium. According to Kellgren-Lawrence (KL) grade of plain radiographs at baseline, the subjects are divided into either KOA onset or deterioration study groups. The disease progression is defined as the changes in both joint space width (JSW) and WOMAC pain score. In addition to radiographic and symptomatic data, the anthropological particulars, history of the knee injury and surgery, metabolic syndrome and living habits were deployed in a multi-layer perceptron (MLP) to predict disease progression in each study group. The relative contributions of each risk factors were weighted via DeepLIFT gradient. Additionally, statistical interactions among risk factors were identified compared. Results: Our model achieved AUC of 0.843 (95% CI 0.824, 0.862) and 0.765 (95% CI 0.756, 0.774) in prediction of KOA onset and deterioration, respectively. For KOA onset prediction, history of injury has attained the highest DeepLIFT gradient except medial joint space narrowing; while for KOA deterioration prediction, diabetes and habit of smoking obtained second and third highest gradients respectively aside from medial joint space narrowing, surpassing the impact of the injury. Conclusion: We developed a machine learning workflow which effectively dissects the risk factors' contributions and their mutual interactions for onset and deterioration of KOA respectively.

Dynamic CTA-Derived Perfusion Maps Predict Final Infarct Volume: The Simple Perfusion Reconstruction Algorithm.

BACKGROUND AND PURPOSE: Infarct core volume measurement using CTP (CT perfusion) is a mainstay paradigm for stroke treatment decision-making. Yet, there are several downfalls with cine CTP technology that can be overcome by adopting the simple perfusion reconstruction algorithm (SPIRAL) derived from multiphase CTA. We compare SPIRAL with CTP parameters for the prediction of 24-hour infarction. MATERIALS AND METHODS: Seventy-two patients had admission NCCT, multiphase CTA, CTP, and 24-hour DWI. All patients had successful/quality reperfusion. Patient-level and cohort-level receiver operator characteristic curves were generated to determine accuracy. A 10-fold cross-validation was performed on the cohort-level data. Infarct core volume was compared for SPIRAL, CTP-time-to-maximum, and final DWI by Bland-Altman analysis. RESULTS: When we compared the accuracy in patients with early and late reperfusion for cortical GM and WM, there was no significant difference at the patient level (0.83 versus 0.84, respectively), cohort level (0.82 versus 0.81, respectively), or the cross-validation (0.77 versus 0.74, respectively). In the patient-level receiver operating characteristic analysis, the SPIRAL map had a slightly higher, though nonsignificant (P < .05), average receiver operating characteristic area under the curve (cortical GM/WM, r = 0.82; basal ganglia = 0.79, respectively) than both the CTP-time-to-maximum (cortical GM/WM = 0.82; basal ganglia = 0.78, respectively) and CTP-CBF (cortical GM/WM = 0.74; basal ganglia = 0.78, respectively) parameter maps. The same relationship was observed at the cohort level. The Bland-Altman plot limits of agreement for SPIRAL and time-to-maximum infarct volume were similar compared with 24-hour DWI. CONCLUSIONS: We have shown that perfusion maps generated from a temporally sampled helical CTA are an accurate surrogate for infarct core.

Mobility performance predicts incident depression: A systematic review and meta-analysis.

Impaired mobility often co-occurs with depression. However, there is no systematic review evidence as to whether mobility impairments precede the onset of depression. The objective of this systematic review and meta-analysis was to evaluate whether mobility impairment could predict incident depression. A systematic search of cohort studies were performed in MEDLINE, EMBASE, CINAHL and PsycINFO. The target population was people with no depressive symptoms at baseline and follow-up for depression or depressive symptoms of at least three months. Of 1061 identified abstracts, 13 studies met the review eligibility criteria. The majority of included studies (8 out of 13) were of high methodological quality. Follow-up periods ranged from 12 months to 16 years. Gait speed was the most consistently reported mobility measure. Participants with slow gait speed were at higher risk of developing depressive symptoms (pooled OR = 1.93, 95%CI: 1.54 to 2.42, 11 studies). This review shows that slow gait speed is predictive of the onset of depressive symptoms. Systematic review registration number: CRD42020153791.

Sphingosine-1-phosphate lyase (SGPL1) deficiency is associated with mitochondrial dysfunction.

Deficiency in Sphingosine-1-phosphate lyase (S1P lyase) is associated with a multi-systemic disorder incorporating primary adrenal insufficiency (PAI), steroid resistant nephrotic syndrome and neurological dysfunction. Accumulation of sphingolipid intermediates, as seen with loss of function mutations in SGPL1, has been implicated in mitochondrial dysregulation, including alterations in mitochondrial membrane potentials and initiation of mitochondrial apoptosis. For the first time, we investigate the impact of S1P lyase deficiency on mitochondrial morphology and function using patient-derived human dermal fibroblasts and CRISPR engineered SGPL1-knockout HeLa cells. Reduced cortisol output in response to progesterone stimulation was observed in two patient dermal fibroblast cell lines. Mass spectrometric analysis of patient dermal fibroblasts revealed significantly elevated levels of sphingosine-1-phosphate, sphingosine, ceramide species and sphingomyelin when compared to control. Total mitochondrial volume was reduced in both S1P lyase deficient patient and HeLa cell lines. Mitochondrial dynamics and parameters of oxidative phosphorylation were altered when compared to matched controls, though differentially across the cell lines. Mitochondrial dysfunction may represent a major event in the pathogenesis of this disease, associated with severity of phenotype.

Periventricular white matter hyperintensity burden and cognitive impairment in early Parkinson's disease.

BACKGROUND AND PURPOSE: This study quantified the total brain and periventricular white matter hyperintensity (WMH) burdens in patients with early Parkinson's disease (PD) and explored their associations with cardiovascular risk factors and cognitive performance. METHODS: A total of 175 non-demented patients with early PD who had undergone baseline brain magnetic resonance imaging were included. Comprehensive neurocognitive testing was conducted to identify PD with mild cognitive impairment (PD-MCI) and to evaluate performances in individual cognitive domains. Cardiovascular risk was expressed as a modified Framingham 10-year cardiovascular risk score (mFRS). RESULTS: A total of 53.7% of this early PD cohort fulfilled the diagnostic criteria for PD-MCI. An increase in mFRS was significantly associated with increases in the total brain WMH (P = 0.015) and periventricular WMH (P = 0.040) burden, independent of age and gender. The periventricular WMH burden was significantly associated with PD-MCI (P = 0.046) in early PD, independent of cardiovascular risk factors. Patients in the 5th quintile of periventricular WMH burden were 8.6 times more likely to have PD-MCI compared with patients in the 1st quintile of periventricular WMH burden (P = 0.004). However, total brain WMH burden was not associated with PD-MCI (P = 0.158). In individual cognitive domains, heavier periventricular WMH burden was associated with worse executive function and visuospatial function independent of cardiovascular risk factors. CONCLUSION: Periventricular WMHs are a useful imaging biomarker for cognitive impairment in early PD. Cardiovascular risk factors, although associated with periventricular WMHs, were unable to fully explain the association between periventricular WMHs and cognitive impairment in early PD.