Venous thromboembolism among Asian populations with localized colorectal cancer undergoing curative resection: is pharmacological thromboprophylaxis required? A systematic review and meta-analysis.

Purpose: We compared the incidence of venous thromboembolism (VTE) among Asian populations with localized colorectal cancer undergoing curative resection with and without the use of pharmacological thromboprophylaxis (PTP). Methods: A comprehensive literature search was undertaken to identify relevant studies published from January 1, 1980 to February 28, 2022. The inclusion criteria were patients who underwent primary tumor resection for localized nonmetastatic colorectal cancer; an Asian population or studies conducted in an Asian country; randomized controlled trials, case-control studies, or cohort studies; and the incidence of symptomatic VTE, deep vein thrombosis, and/or pulmonary embolism as the primary study outcomes. Data were pooled using a random-effects model. This study was registered in PROSPERO on October 11, 2020 (No. CRD42020206793). Results: Seven studies (2 randomized controlled trials and 5 observational cohort studies) were included, encompassing 5,302 patients. The overall incidence of VTE was 1.4%. The use of PTP did not significantly reduce overall VTE incidence: 1.1% (95% confidence interval [CI], 0%-3.1%) versus 1.9% (95% CI, 0.3%-4.4%; P = 0.55). Similarly, PTP was not associated with significantly lower rates of symptomatic VTE, proximal deep vein thrombosis, or pulmonary embolism. Conclusion: The benefit of PTP in reducing VTE incidence among Asian patients undergoing curative resection for localized colorectal cancer has not been clearly established. The decision to administer PTP should be evaluated on a case-bycase basis and with consideration of associated bleeding risks.

Determining the Need for Metastatic Staging in Patients with Bilateral Breast Cancers.

Introduction: Bilateral breast cancers (BBC) diagnosed at an interval apart are uncommon. While metastatic staging guidelines are established in patients with unilateral breast cancer, its role in BBC diagnosed at an interval apart is unclear. We aim to identify the subgroup who would benefit from metastatic staging at contralateral cancer diagnosis. Methods: Eligible patients were divided into three categories: (A) ipsilateral invasive cancer and contralateral ductal carcinoma in situ (DCIS), (B) bilateral invasive cancers and (C) ipsilateral DCIS and contralateral invasive cancer and reviewed retrospectively. We excluded patients with bilateral DCIS, synchronous BBC diagnosed within 6 months from first cancer, patients who were stage IV at first cancer diagnosis and patients with recurrence prior to contralateral cancer. Results: Of 4516 newly diagnosed breast cancer patients, 79 patients were included. Systemic metastasis occurred in 15.6% of patients in Group B. Having nodal positivity of either cancer which were diagnosed ≤30 months apart and nodal positivity of only the contralateral cancer when diagnosed >30 months apart was significantly associated with systemic metastasis (p = 0.0322). Conclusions: Both the nodal status and a 30 months cut-off time interval between the two cancers can be used to identify patients who will benefit from metastatic staging. This finding requires validation in larger studies.

Use of axillary ultrasound to guide breast cancer management in the genomic assay era.

INTRODUCTION: Chemotherapy is conventionally offered to non-stage IV breast cancer patients with metastatic nodes. However, the RxPONDER trial showed that chemotherapy can be omitted in selected patients with 1-3 metastatic nodes if the 21-gene assay recurrence score is ≤25. We aimed to investigate if axillary ultrasound can identify this group of patients with limited nodal burden so that they can undergo upfront surgery followed by gene assay testing, to potentially avoid chemotherapy. METHODS: T1-3, node positive, hormone receptor-positive and HER2-negative breast cancer patients ≥50 years old with axillary lymph node dissection (ALND) were reviewed from 2 centres. Patients with neoadjuvant chemotherapy and bilateral cancers were excluded. Number of ultrasound-detected abnormal axillary nodes, demographic and histological parameters were correlated with the number of metastatic nodes found on ALND. RESULTS: 138 patients were included, 59 (42.8%) and 79 (57.2%) patients had 1-3 and >3 metastatic nodes on ALND respectively. On logistic regression and ROC analysis, the number of ultrasound-detected abnormal nodes was significant (p < 0.001) for predicting limited nodal burden (ROC AUC = 0.7135). Probabilities of <4 metastatic nodes with ultrasound cut-offs of 5, 6 and 8 abnormal nodes were 0.057, 0.026 and 0.005 respectively, with 100% specificity. CONCLUSION: A cut-off of ≤5 ultrasound-detected abnormal nodes can distinguish between patients with limited versus high nodal burden, with high specificity. Hence, incorporating the number of abnormal ultrasound-detected nodes into clinical practice may prove useful in guiding between upfront surgery and gene assay testing or neoadjuvant chemotherapy in this group of patients.

Preventing perioperative hypothermia in children through implementation of customised guidelines.

INTRODUCTION: Perioperative hypothermia (PH) is common in children and associated with adverse clinical outcomes. Guidelines to prevent PH are mainly developed for adults and differ among institutions. We aimed to evaluate the effectiveness of customised guidelines in reducing PH in our paediatric population and the impact of cost considerations on physician practice. METHODS: Patients aged ≤16 years undergoing general anaesthesia in our tertiary paediatric hospital were prospectively recruited in this cohort study. Patient demographics, surgical procedures, anaesthesia details and temperature control measures were recorded. Data collection occurred over four phases: Phases 1 and 2 comprised standard management, while Phases 3 and 4 occurred following guidelines implementation. Sensors for continuous core temperature monitoring were provided free to patients during Phases 1 and 3, but were charged during Phases 2 and 4. The main outcome was occurrence of PH, defined as core temperature <36°C at any point from induction of anaesthesia to discharge from the postanaesthetic care unit. The impact of guidelines implementation and cost considerations influencing physician practice on PH outcomes was also analysed. RESULTS: Data from 3917 patients was analysed (1766 in Phase 1, 679 in Phase 2, 706 in Phase 3 and 766 in Phase 4). Guidelines implementation decreased PH incidence from 11.0% to 6.79% (odds ratio [OR] 0.63, 95% confidence interval [CI] 0.50-0.80, P = 0.0002). Free sensors increased the odds of detecting PH (OR 1.48, 95% CI 1.17-1.88, P = 0.001). With guidelines implementation, there was greater reduction in PH with free sensors (OR 0.64, 95% CI 0.47-0.88, P = 0.0055) compared to chargeable sensors (OR 0.75, 95% CI 0.50-1.11, P = 0.1471). CONCLUSIONS: Customised guidelines facilitated a sustained reduction of hypothermia in our paediatric surgical patients, although its impact was reduced by cost considerations.

Outcomes and cost analysis of single-embryo transfer versus double-embryo transfer.

BACKGROUND: Studies had compared single-embryo transfer to double-embryo transfer with cleavage stage embryos and found that while single-embryo transfer was less costly, it was also associated with a lower live birth rate than double-embryo transfer. A single blastocyst transfer has been shown to improve the live birth rate per cycle compared to single-embryo transfer at cleavage stage. OBJECTIVES: To compare live birth rates and real costs of elective single-embryo transfer to double-embryo transfer and to determine the incremental cost-effectiveness ratio of these two strategies in an unselected pool of women in a single center. DESIGN: Retrospective study. METHODS: We analyzed data of 4232 women who underwent their first fresh in vitro fertilization/intra-cytoplasmic sperm injection cycles with at least two embryos available for transfer in KK Women's and Children's Hospital from 2010 to 2017. RESULTS: Five hundred and sixty-four women underwent elective single-embryo transfer and 3668 women underwent double-embryo transfer. One hundred and fifty-six women who failed to achieve a live birth in their fresh elective single-embryo transfer cycle underwent a sequential thaw single-embryo transfer cycle. Live birth rate of fresh elective single-embryo transfer was significantly higher at 41.3% than that of double-embryo transfer at 32.6%. Cumulative live birth rate for sequential elective single-embryo transfer (fresh elective single-embryo transfer + thaw single-embryo transfer) was 47.9%. After accounting for variables which may affect live birth rates such as age and stage of embryo transfer, the odds of achieving a live birth from double-embryo transfer was 24% lower than that from sequential single-embryo transfer, although not statistically significant. For every live birth gained from an elective single-embryo transfer compared to double-embryo transfer, cost savings were S$20,172 per woman. If a woman had to have a sequential single-embryo transfer after a failed single-embryo transfer in her fresh cycle, cost savings were reduced to S$1476 per woman. CONCLUSION: Single-embryo transfer is a dominant strategy in an unselected population and adopting it in assisted reproductive treatments (ART) can produce cost savings without compromising on live birth rates.

Association of leadless pacing with ventricular and valvular function.

BACKGROUND: Traditional transvenous pacemakers are associated with worsening tricuspid valve function due to lead-related leaflet impingement, as well as ventricular dysfunction related to electromechanical dyssynchrony from chronic right ventricular (RV) pacing. The association of leadless pacing with ventricular and valvular function has not been well established. We aimed to assess the association of leadless pacemaker placement with changes in valvular regurgitation and ventricular function. METHODS AND RESULTS: Echocardiographic features before and after leadless pacemaker implant were analyzed in consecutive patients who received a leadless pacemaker with pre- and postprocedure echocardiography at Duke University Hospital between November 2014 and November 2019. Valvular regurgitation was graded ordinally from 0 (none) to 3 (severe). Among 54 patients, the mean age was mean age was 70.1 ± 14.3 years, 24 (44%) were women, and the most frequent primary pacing indication was complete heart block in 24 (44%). The median RV pacing burden was 45.4 (interquartile range [IQR] 3.5-97.0). On echocardiogram performed 8.9 months (IQR 4.5-14.5) after implant, there was no change in the average severity of tricuspid regurgitation (mean change 0.07 ± 1.15, p = .64) from pre-procedure echocardiogram. We observed a decrease in the average left ventricular ejection fraction (LVEF) (52.3 ± 9.3 to 47.9 ± 12.1, p = .0019) and tricuspid annular plane systolic excursion (TAPSE) (1.8 ± 0.6 to 1.6 ± 0.4, p = .0437). Thirteen patients (24%) had absolute drop in LVEF of ≥10%. CONCLUSION: We did not observe short term worsening valvular function in patients with leadless pacemakers. However, consistent with the pathophysiologic impact of RV pacing, leadless pacing was associated with a reduction in biventricular function.

Serial deep gray nuclear DTI changes in Parkinson's disease over twelve years.

Background: Deep gray nuclear pathology relates to motor deterioration in idiopathic Parkinson's disease (PD). Inconsistent deep nuclear diffusion tensor imaging (DTI) findings in cross-sectional or short-term longitudinal studies have been reported. Long-term studies in PD are clinically challenging; decade-long deep nuclear DTI data are nonexistent. We investigated serial DTI changes and clinical utility in a case-control PD cohort of 149 subjects (72 patients/77 controls) over 12 years. Methods: Participating subjects underwent brain MRI at 1.5T; DTI metrics from segmented masks of caudate, putamen, globus pallidus and thalamus were extracted from three timepoints with 6-year gaps. Patients underwent clinical assessment, including Unified Parkinson Disease Rating Scale Part 3 (UPDRS-III) and Hoehn and Yahr (H&Y) staging. A multivariate linear mixed-effects regression model with adjustments for age and gender was used to assess between-group differences in DTI metrics at each timepoint. Partial Pearson correlation analysis was used to correlate clinical motor scores with DTI metrics over time. Results: MD progressively increased over time and was higher in the putamen (p < 0.001) and globus pallidus (p = 0.002). FA increased (p < 0.05) in the thalamus at year six, and decreased in the putamen and globus pallidus at year 12. Putaminal (p = 0.0210), pallidal (p = 0.0066) and caudate MD (p < 0.0001) correlated with disease duration. Caudate MD (p < 0.05) also correlated with UPDRS-III and H&Y scores. Conclusion: Pallido-putaminal MD showed differential neurodegeneration in PD over 12 years on longitudinal DTI; putaminal and thalamic FA changes were complex. Caudate MD could serve as a surrogate marker to track late PD progression.

Reducing blood sample hemolysis in the emergency department using S-Monovette® in aspiration mode.

Background: Blood sample hemolysis continues to be a significant problem in clinical practice. In vitro hemolysis rates up to 77% have been reported in literature. The use of manual aspiration techniques for blood sampling has previously been shown to reduce the burden of erythrocyte injury in the pre-analytical phase compared to the vacuum collection technique. This study compares the hemolysis rates between two blood sampling methods: 5.0 ml BD Vacutainer® SST™ (BDV) and 4.9 ml S-Monovette® serum gel tubes in aspiration mode (SMA). Methods: This was a prospective randomised controlled study conducted in an Emergency department (ED). A convenience sample of 191 adult patients, aged 18-90 years old, presenting at the ED and requiring blood samples for serum electrolyte was included in the study. Paired blood samples were obtained through an intravenous cannula from each patient with randomised order of blood draw using SMA or BDV. Patient data was obtained and hemolysis index (HI), serum lactate dehydrogenase (LDH), and serum potassium (K) levels measured. Results: The adjusted mean HI (35.2 vs 21.5 mg/dL, p < 0.001), serum K (4.38 vs 4.16 mmol/L, p < 0.001) and LDH levels (259.6 vs 228.4 U/L, p < 0.001) were significantly higher in blood samples taken using BDV compared to SMA. The frequency of severely hemolyzed (>150 mg/dL) samples was also higher in blood collected using BDV (16.2%) compared to SMA (0%). Conclusions: The burden of hemolysis in blood samples taken from IV cannulae can be effectively reduced with the use of manual aspiration using the S-Monovette® blood collection system as compared to BD-Vacutainer.

A comparison of the outcomes of a novel technique of Mini-Incision and Self-Express (MISE) for breast abscess with the conventional techniques: a retrospective comparative cohort study.

Conventional techniques for treatment of breast abscess, such as incision and drainage (I&D) and needle aspiration, have disadvantages. The authors aimed to compare the outcomes of a novel technique of bedside mini-incision and self-express (MISE) for breast abscess with the conventional techniques. Methods: Patients with a pathologically confirmed breast abscess were retrospectively identified. Patients with mastitis, granulomatous mastitis, breast fillers with infection, ruptured abscess prior to intervention, other interventions or bilateral breast infection were excluded. Data collected included patient demographics, radiological features such as size and number of abscess, treatment modality, microbiological results and clinical outcomes. These outcomes were then compared between the patients with MISE, I&D and needle aspiration. Results: Twenty-one patients were included. The mean age was 31.5 years old (range: 18-48). Mean abscess size was 57.4 mm (range: 24-126). 5 (23.8%), 11 (52.4%) and 5 (23.8%) had MISE, needle aspiration and I&D, respectively. Average duration of antibiotics was 1.8, 3.9 and 2.6 weeks for MISE, needle aspiration and I&D groups, respectively, which was statistically significant after adjusting for confounders (P=0.024). Mean duration of recovery was 2.8, 7.8 and 6.2 weeks for the MISE, needle aspiration and I&D groups, respectively (P=0.027), after adjusting for confounders. Conclusion: MISE, in suitable patients, results in shorter recovery time and lesser antibiotics usage, compared with the conventional techniques.

Early metabolic derangements and unfavorable outcomes in pediatric traumatic brain injury: a retrospective multi-center cohort study.

Background: To study the association in moderate and severe pediatric traumatic brain injury (TBI) between hyperglycemia, hyperlactatemia, acidosis and unfavorable outcome, as assessed by Pediatric Cerebral Performance Category (PCPC) on discharge from the pediatric intensive care unit (PICU). Methods: Children <16 years old with TBI and Glasgow Coma Scale (GCS) ≤13 in an Asian multi-center PICU TBI cohort from January 2014 to October 2017 were included in this study. We defined unfavorable outcome as PCPC ≥3-moderate disability, severe disability, vegetative state, and death. We performed logistic regression to investigate the association between metabolic changes with unfavorable outcome. We divided hyperglycemia (glucose >11.1 mmol/L) during PICU admission into early-onset (within 24 h), late-onset (beyond 48 h) and persistent (throughout first 72 h). Results: Among the 305 children analyzed, 136 (44.6%) had unfavorable outcome. Children with unfavorable outcome were more likely to have early hyperglycemia (75/136, 55.1% vs. 33/169, 19.5%; P<0.001), high lactate levels >2.0 mmol/L (74/136, 54.4% vs. 56/169, 32.5%; P<0.001) and initial acidosis (85/136, 62.5% vs. 78/169, 56.1%; P=0.003) compared to those with favorable outcome. After adjusting for gender, GCS ≤8 and presence of polytrauma, early hyperglycemia [adjusted odds ratio (aOR) =3.68, 95% CI: 2.12-6.39, P<0.001] and late hyperglycemia (aOR =13.30, 95% CI: 1.64-107.8, P=0.015] were independently associated with unfavorable outcome. All children with persistent hyperglycemia died. Conclusions: We described unfavorable outcome in pediatric TBI especially with persistent hyperglycemia. Future trials should investigate the causal relationship between glycemic trends, early intervention and outcome in this cohort.

Early Neurodevelopmental Outcomes Following Exposure to General Anesthesia in Infancy: EGAIN, a Prospective Cohort Study.

BACKGROUND: General anesthesia (GA) is known to worsen neural outcomes in animals, but human research assessing early-life GA exposure and neurodevelopment show inconsistent findings. We investigated the effects of a single GA exposure for minor surgery on the neurodevelopment of healthy children at multiple time-points, using clinical assessments along with behavioral and neurophysiological measures rarely used in human research. METHODS: GA-exposed children were a prospective cohort of 250 full-term, healthy infants who underwent GA for minor surgery before 15 months. Nonexposed children were from a separate cohort of similar age, sex, ethnicity, and maternal education. In both cohorts, clinical measures (Bayley Scales of Infant and Toddler Development-III [BSID-III] and Child Behavior Checklist [CBCL1½-5]) were assessed at 24 months, and experimental tests (memory and attentional) and neurophysiology (event-related potentials) at 6 and 18 months. RESULTS: At 24 months, there were no differences between GA-exposed and nonexposed children in the cognitive, language, motor, and socioemotional domains of the BSDI-III; however, GA-exposed children had poorer parental-reported scores in BSID-III general adaptability (94.2 vs. 99.0 [mean difference, 4.77; 97.3% confidence interval, -9.29, -0.24]; P =0.020) and poorer internalizing behavior scores on CBCL1½-5 (52.8 vs. 49.4 [mean difference, 3.35; 97.3% confidence interval, 0.15-6.55]; P =0.021). For experimental measures, GA-exposed children showed differences in 4 tests at 6 and 18 months. CONCLUSIONS: GA-exposed children did not differ from unexposed children in cognitive, language or motor outcomes at 24 months, but exhibited poorer parent-reported behavior scores. Differences in infant behavior and neurophysiology were detected at 6 and 18 months. Neurophysiological assessments may complement clinically relevant assessments to provide greater insights into neurodevelopment following early GA exposure.

Healthcare utilization and health-related quality of life of severe asthma patients in Singapore.

BACKGROUND: Notwithstanding unequivocal consensus on the disproportionate effect of severe asthma (SA) on asthma morbidity, healthcare utilization, quality of life, work impairment and socioeconomic burden, the burden of SA patients in Singapore has not been appraised. OBJECTIVES: To determine the burden of disease and extent of quality of life impairment in SA patients in Singapore. METHODS: A cross-sectional analysis of SA patients seen in Singapore General Hospital (2020-2021) to investigate emergency healthcare utilization, oral corticosteroid (OCS) burden and health-related quality of life (HRQoL) with primary endpoint EuroQoL-5 Dimension three-level (EQ-5D-3L) scores. The empirical measurement properties of the EQ-5D utility index in SA were comprehensively assessed through multivariate regression analyses. RESULTS: A total of 336 SA patients were recruited, 51.2% of SA patients had at least one acute healthcare resource utilization during the previous year, with 25.6% of patients having an emergency healthcare visit to the hospital. Overall mean (SD) EQ-5D-3L and EQ-5D-3L utility scores in SA patients were 6.22 (1.51) and 0.77 (0.30), respectively. EQ-5D utility scores were 0.14 lower in uncontrolled vs controlled asthma and 0.09 lower in the presence of severe exacerbation, whereas barely changed by maintenance OCS dose and airflow limitation. CONCLUSION: SA patients were found to have high disease burden, high healthcare resource utilization and OCS use, low biologics usage, poor HRQoL and utility in comparison with other chronic diseases.

Is Metastatic Staging Needed for All Patients with Synchronous Bilateral Breast Cancers?

BACKGROUND: Patients with bilateral breast cancers are uncommon and are associated with a poorer prognosis. While metastatic staging guidelines in patients with unilateral cancer were established, the indication of metastatic staging in patients with bilateral breast cancers is unclear. We aimed to determine which patients with synchronous bilateral breast cancers require metastatic staging at diagnosis. This is the first such reported study, to the best of our knowledge. METHODS: A retrospective review of newly diagnosed synchronous bilateral invasive breast cancer patients at our institution was performed. We excluded patients with malignant phyllodes or no metastatic staging. Patients' demographics and pathological and staging results were analysed to determine the group of bilateral breast cancer patients who required metastatic staging. RESULTS: A total of 92 patients with synchronous bilateral invasive cancers were included. The mean age was 58 years old, and 64.1% had bilateral invasive ductal carcinoma. 23.9% had systemic metastasis. Nodal status was statistically significant for systemic metastasis on staging (p = 0.0081), with only three patients (3.3%) having negative nodal status and positive metastatic staging. These three patients, however, showed symptoms of distant metastasis. 92.3% of patients with negative nodes also had negative metastatic staging. Using negative nodal status as a guide avoided metastatic staging in 40.4% of all patients. CONCLUSIONS: Negative nodal status was the most predictive factor for no systemic metastasis on staging in patients with synchronous bilateral invasive breast cancers. Hence, metastatic staging could be reserved for patients with symptoms of systemic metastasis and/or metastatic nodes. This finding could be validated in larger studies.

Receiver operating characteristic analysis using a novel combined thermal and ultrasound imaging for assessment of disease activity in rheumatoid arthritis.

We aim to determine whether combined thermal and ultrasound (CTUS) imaging can identify rheumatoid arthritis (RA) patients with at least moderate disease activity (DAS28 > 3.2). Temperature differences of maximum (Tmax), average (Tavg) and minimum (Tmin) temperatures from a control temperature at 22 joints (bilateral hands) were summed up to derive the respective MAX, AVG and MIN per patient. MAX (PD), AVG (PD) and MIN (PD) are CTUS results derived by multiplying MAX, AVG and MIN by a factor of 2 when a patient's total ultrasound power Doppler (PD) joint inflammation score > median score, which otherwise remained unchanged. Receiver operating characteristic (ROC) analysis was used to determine whether CTUS imaging can identify patients with DAS28 > 3.2. In this cross-sectional study, 814 joints were imaged among 37 RA patients (mean disease duration, 31 months). CTUS (but not single modality) imaging parameters were all significantly greater comparing patients with DAS28 > 3.2 versus those with DAS28 ≤ 3.2 (all P < 0.01). Area under the ROC curves (AUCs) using cut-off levels of ≥ 94.5, ≥ 64.6 and ≥ 42.3 in identifying patients with DAS28 > 3.2 were 0.73 , 0.76 and 0.76 for MAX (PD), AVG (PD) and MIN (PD), respectively (with sensitivity ranging from 58 to 61% and specificity all 100%). The use of CTUS in detecting a greater severity of joint inflammation among patients with at least moderate disease activity (DAS28 > 3.2) appears promising and will require further validation in independent RA cohorts.

Prediction of subclinical atherosclerosis in low Framingham risk score individuals by using the metabolic syndrome criteria and insulin sensitivity index.

Background: Subclinical atherosclerosis can be present in individuals with an optimal cardiovascular risk factor profile. Traditional risk scores such as the Framingham risk score do not adequately capture risk stratification in low-risk individuals. The aim of this study was to determine if markers of metabolic syndrome and insulin resistance can better stratify low-risk individuals. Methods: A cross-sectional study of 101 healthy participants with a low Framingham risk score and no prior morbidities was performed to assess prevalence of subclinical atherosclerosis using computed tomography (CT) and ultrasound. Participants were compared between groups based on Metabolic Syndrome (MetS) and Insulin-Sensitivity Index (ISI-cal) scores. Results: Twenty three individuals (23%) had subclinical atherosclerosis with elevated CT Agatston score ≥1. Presence of both insulin resistance (ISI-cal <9.23) and fulfillment of at least one metabolic syndrome criterion denoted high risk, resulting in significantly improved AUC (0.706 95%CI 0.588-0.822) over the Framingham risk score in predicting elevated CT Agatston score ≥1, with net reclassification index of 50.9 ± 23.7%. High-risk patients by the new classification also exhibited significantly increased carotid intima thickness. Conclusions: The overlap of insulin resistance and presence of ≥1 criterion for metabolic syndrome may play an instrumental role in identifying traditionally low-risk individuals predisposed to future risk of atherosclerosis and its sequelae.

Gender differences in fasting and postprandial metabolic traits predictive of subclinical atherosclerosis in an asymptomatic Chinese population.

The prediction utility of Framingham Risk Score in populations with low conventional cardiovascular risk burden is limited, particularly among women. Gender-specific markers to predict cardiovascular risk in overtly healthy people are lacking. In this study we hypothesize that postprandial responses triggered by a high-calorie meal test differ by gender in their ability to triage asymptomatic subjects into those with and without subclinical atherosclerosis. A total of 101 healthy Chinese subjects (46 females, 55 males) at low risk of coronary heart disease completed the study. Subjects underwent cardiovascular imaging and postprandial blood phenotyping after consuming a standardized macronutrient meal. Prediction models were developed using logistic regression and subsequently subjected to cross-validation to obtain a de-optimized receiver operating characteristic (ROC) curve. Distinctive gender differences in postprandial trajectories of glucose, lipids and inflammatory markers were observed. We used gender-specific association with different combinations of postprandial predictors to develop 2 models for predicting risk of subclinical atherosclerosis in males (ROC AUC = 0.7867, 95% CI 0.6567, 0.9166) and females (ROC AUC = 0.9161, 95% CI 0.8340, 0.9982) respectively. We report novel postprandial models for predicting subclinical atherosclerosis in apparently healthy Asian subjects using a gender-specific approach, complementing the conventional Framingham Risk Score.Clinical Trial Registration: The trial was registered at clinicaltrials.gov as NCT03531879.

Patterns of breast cancer second recurrences in patients after mastectomy.

INTRODUCTION: Little is known about second recurrences in breast cancer patients, especially in patients with mastectomy. We aimed to determine the risk factors, prevalence and patterns of second recurrence in mastectomy patients after first recurrence. METHODS: Stage I-III breast cancer patients treated at a tertiary institution from 1st September 2005 to 31st October 2017 and developed first and second recurrences after mastectomy were retrospectively reviewed. We excluded patients with bilateral cancers and patients who were lost to follow-up. The demographics, pathological and recurrence data were collected from a prospectively maintained database and analysed. RESULTS: Of the 1619 mastectomy patients, 214 (13.2%) patients developed recurrences at a mean 39.9 months from primary cancer diagnosis. 23, 8 and 183 had isolated chest wall recurrences (CWR), regional and systemic metastases, respectively. Excluding 2 CWR patients without surgery, second recurrences occurred in 3/21 (14.3%) and 3/8 (37.5%) in patients with CWR and regional metastasis at 27.7 months (range: 5-42) and 32 months (range: 18-40), respectively. In both groups, systemic metastasis as second recurrence occurred within 2 years after first recurrence, whilst locoregional second recurrences occurred later. No risk factors for second recurrence were identified. CONCLUSION: In patients with mastectomy, second recurrences occurred in 20.7% of patients with treated locoregional first recurrence, with no risk factors identified. Systemic metastases manifesting as second recurrence occurred in the first 2 years after first recurrence. Continued clinical surveillance and restaging patients in the first 2 years after first locoregional recurrence may enable early prognostication and treatment with the newer metastatic drugs.

Epidemiology and outcome of septic arthritis in childhood: a 16-year experience and review of literature.

INTRODUCTION: Septic arthritis (SA) is a devastating infection with a high rate of sequelae. The aim of this retrospective study was to determine the epidemiology, clinically significant sequelae and risk factors for developing these sequelae in children admitted to our hospital with SA. METHODS: Patients with bacteriologically and/or radiologically confirmed SA from January 1999 to December 2014 were identified from discharge and laboratory records. Data was collected through a retrospective review of the case notes. RESULTS: A total of 75 patients (62.7% male) met the inclusion criteria. The median age at presentation was six years (range two weeks to 15 years), and six patients were neonates. Microbiologic aetiology was determined in 40 (53.3%) patients, with Staphylococcus aureus being the most common organism. 68.0% of the patients underwent arthrotomy, and the average hospital stay was 15.3 days. Sequelae of SA were observed in nine patients on follow-up. Univariate and multivariate statistical analyses showed that young age, pyogenic bacterial isolation and concomitant osteomyelitis were significant risk factors for developing sequelae. CONCLUSION: Our study demonstrated that young age, pyogenic bacterial isolation and concomitant osteomyelitis are associated with a high risk of sequelae. Timely microbiologic diagnosis by novel polymerase chain reaction methods and the use of magnetic resonance imaging in high-risk children to identify adjacent infection could possibly prevent lifelong disabling sequelae in SA.

Patient-reported outcomes of a phase II neoadjuvant apalutamide (ARN-509) and radical prostatectomy in treatment of intermediate- to high-risk prostate cancer (NEAR) trial.

OBJECTIVE: The NEAR trial is a single-arm phase II trial investigating the efficacy of neoadjuvant apalutamide and radical prostatectomy in the treatment of D'Amico intermediate- to high-risk prostate cancer. This publication focuses on health-related quality of life (HRQoL) during 12 weeks of neoadjuvant apalutamide treatment. METHODS: From 2017 to 2019, 30 suitable patients received neoadjuvant apalutamide 240 mg once daily for 12 weeks followed by radical prostatectomy (ClinicalTrials.gov Identifier: NCT03124433). Patient-reported quality of life outcomes was analyzed using European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core Module (EORTC QLQ-C30), EORTC Quality of Life Questionnaire Prostate Module (QLQ-PR25), and Sexual Health Inventory for Men questionnaire (SHIM) at weeks 0,4,12, and 20 of the study. RESULTS: Thirty patients completed 12 weeks of apalutamide therapy and data analyzed for 29 with complete datasets. Neoadjuvant apalutamide therapy was associated with no clinically significant negative impact on patients' global health and QoL scores. Deteriorations in mean scores of functional and symptom scales of QLQ-C30 questionnaire were statistically significant (p = 0.011 and p = 0.008, respectively) but were not clinically meaningful. Patients were also affected by fatigue (p = 0.012), cognitive function (p = 0.038), reduced role functioning (p = 0.025), and lower SHIM scores (p < 0.001). Median daily step count reduced from 8228/day to 6001/day per day (p = 0.063), while BMI and body weight reduction were observed (statistically but not clinically significant). CONCLUSION: During 12 weeks of neoadjuvant apalutamide in organ-confined prostate cancer, the overall patient-reported HRQoL outcomes were maintained, but fatigue and sexual dysfunction were observed in those patients.

Poor utility of current nomograms assessing the risk of intraoperative blood transfusion in patients undergoing liver resection for hepatocellular carcinoma and proposal of a new model.

BACKGROUND: The Memorial Sloan Kettering Cancer Center nomogram, the predictive scoring system of Yamamoto et al, and the 3-point transfusion risk score of Lemke et al are models used to determine the probability of receiving intraoperative blood transfusion in patients undergoing liver resection. However, the external validity of these models remains unknown. The objective of this study was to evaluate their predictive performance in an external cohort of patients with hepatocellular carcinoma. We also aimed to identify predictors of blood transfusion and develop a new predictive model for blood transfusion. METHODS: Post hoc analysis of our prospective database of 1,081 patients undergoing liver resection for hepatocellular carcinoma from 2001 to 2018. The predictive performance of current prediction models was evaluated using C statistics. Demographic and clinical variables as predictors of blood transfusion were assessed. Using logistic regression, an alternative model was created. RESULTS: The Lemke transfusion risk score performed better than the Memorial Sloan Kettering Cancer Center nomogram (0.69, 95% confidence interval 0.66-0.73 vs 0.66, 95% liver resection 0.62-0.69) (P < .001). The model from Yamamoto et al performed comparably with no statistically significant differences found through pairwise comparison. In our alternative model, hemoglobin level, albumin level, liver resection type, and tumor size were independent predictors of blood transfusion. The new HATS model obtained a C statistic of 0.74 (95% confidence interval 0.71-0.78), performing significantly better than the previous 3 models (P ≤ 0.001 for all). CONCLUSION: The existing Memorial Sloan Kettering Cancer Center, Yamamoto et al, and Lemke et al had nomograms with the suboptimal accuracy of predicting risk of intraoperative blood transfusion in patients undergoing liver resection for hepatocellular carcinoma. The proposed HATS model was more accurate at predicting patients at risk of blood transfusion.