Predictors and outcomes of withholding and withdrawal of life-sustaining treatments in intensive care units in Singapore: a multicentre observational study.

BACKGROUND: Clinical practice guidelines on limitation of life-sustaining treatments (LST) in the intensive care unit (ICU), in the form of withholding or withdrawal of LST, state that there is no ethical difference between the two. Such statements are not uniformly accepted worldwide, and there are few studies on LST limitation in Asia. This study aimed to evaluate the predictors and outcomes of withholding and withdrawal of LST in Singapore, focusing on the similarities and differences between the two approaches. METHODS: This was a multicentre observational study of patients admitted to 21 adult ICUs across 9 public hospitals in Singapore over an average of three months per year from 2014 to 2019. The primary outcome measures were withholding and withdrawal of LST (cardiopulmonary resuscitation, invasive mechanical ventilation, and vasopressors/inotropes). The secondary outcome measure was hospital mortality. Multivariable generalised mixed model analysis was used to identify independent predictors for withdrawal and withholding of LST and if LST limitation predicts hospital mortality. RESULTS: There were 8907 patients and 9723 admissions. Of the former, 80.8% had no limitation of LST, 13.0% had LST withheld, and 6.2% had LST withdrawn. Common independent predictors for withholding and withdrawal were increasing age, absence of chronic kidney dialysis, greater dependence in activities of daily living, cardiopulmonary resuscitation before ICU admission, higher Acute Physiology and Chronic Health Evaluation (APACHE) II score, and higher level of care in the first 24 h of ICU admission. Additional predictors for withholding included being of Chinese race, the religions of Hinduism and Islam, malignancy, and chronic liver failure. The additional predictor for withdrawal was lower hospital paying class (with greater government subsidy for hospital bills). Hospital mortality in patients without LST limitation, with LST withholding, and with LST withdrawal was 10.6%, 82.1%, and 91.8%, respectively (p < 0.001). Withholding (odds ratio 13.822, 95% confidence interval 9.987-19.132) and withdrawal (odds ratio 38.319, 95% confidence interval 24.351-60.298) were both found to be independent predictors of hospital mortality on multivariable analysis. CONCLUSIONS: Differences in the independent predictors of withholding and withdrawal of LST exist. Even after accounting for baseline characteristics, both withholding and withdrawal of LST independently predict hospital mortality. Later mortality in patients who had LST withdrawn compared to withholding suggests that the decision to withdraw may be at the point when medical futility is recognised.

Association of intrinsic capacity with functional ability, sarcopenia and systemic inflammation in pre-frail older adults.

Background: Decline in intrinsic capacity (IC) has been shown to accelerate progression to disability. The study aims to explore association of IC composite score with functional ability, sarcopenia and systemic inflammation in pre-frail older adults. Methods: Cross-sectional study of pre-frail older adults ≥60 years old recruited from the community and primary care centers. Composite scores of four domains of IC were measured: locomotion, vitality, cognition and psychological. FRAIL scale was used to define pre-frailty. Muscle mass was measured using the bioelectrical impedance analysis. Systemic inflammation biomarkers [Interleukin-6 (IL-6), Interleukin-10 (IL-10), Tumor Necrosis Factor Alpha (TNF-α), and Growth differentiated factor 15 (GDF-15)] were measured. Participants in the lowest tertile (T1) exhibited greater decline in IC. Results: A total of 398 pre-frail older adults were recruited, mean age was 72.7 ± 5.8 years, 60.1% female, education level 7.8 years, and 85.2% were of Chinese ethnicity. A total of 75.1% had decline in locomotion, 40.5% in vitality, 53.2% in cognition and 41.7% in psychological domain. A total of 95% had decline in at least one domain. T1 was significantly associated with ADL impairment (aOR 3.36, 95% CI 1.78-6.32), IADL impairment (aOR 2.37, 95% CI 1.36-4.13), poor perceived health (aOR 0.96, 95% CI 0.95-0.98), fall (aOR 1.63, 95% CI 1.05-2.84), cognitive impairment (aOR 8.21, 95% CI 4.69-14.39), depression (aOR 101.82, 95% CI 33.62-308.37), and sarcopenia (aOR 2.40, 95% CI 1.60-5.45). T1 had significant associations with GDF-15, IL-10, and IL-10 to TNF-α ratio. Conclusion: Decline in IC composite score among pre-frail older adults was associated with functional limitation, sarcopenia, and systemic inflammation.

Off-clamp vs on-clamp robot-assisted partial nephrectomy: a systematic review and meta-analysis.

OBJECTIVE: To compare intra- and postoperative outcomes between off-clamp and on-clamp robot-assisted partial nephrectomy (RAPN), using data from randomised controlled trials (RCTs) or covariate-matched studies (propensity score-matched or matched-pair analysis). METHODS: A Preferred Reporting Items for Systematic Reviews and Meta-Analyses-compliant literature review was conducted on PubMed, EMBASE, Scopus and CENTRAL for relevant studies comparing off-clamp to on-clamp RAPN. Primary outcomes were estimated blood loss, postoperative percentage decrease in estimated glomerular filtration rate (eGFR), and margin positive rate. Secondary outcomes were operative time, postoperative eGFR, length of stay, all postoperative complications, major complications, and need for transfusion. Random-effects meta-analyses were performed to generate mean differences (MDs) or odds ratios (ORs). RESULTS: A total of 10 studies (2307 patients) were shortlisted for analysis. There was no significant difference in estimated operative blood loss between off-clamp and on-clamp RAPN (MD 21.9 mL, 95% confidence interval [CI] -0.9 to 44.7 mL; P = 0.06, I2 = 58%). Off-clamp RAPN yielded a smaller postoperative eGFR deterioration (MD 3.10%, 95% CI 1.05-5.16%; P = 0.008, I2 = 13%) and lower odds of margin positivity (OR 0.62, 95% CI 0.40-0.94; P = 0.03, I2 = 0%). No significant differences were found for all secondary outcomes. CONCLUSIONS: Off-clamp and on-clamp RAPN are similarly effective approaches for selected renal masses. Within the classic trifecta of PN outcomes, off-clamp RAPN yields similar rates of perioperative complications and may possibly offer better preservation of renal function and reduced margin-positive rates.

Association between different skeletal muscle mass indices, physical function, and inflammation in obese pre-frail older adults.

OBJECTIVES: There is lack of consensus on measurement of muscle mass and quality in obese older adults. We aim to evaluate the association of four muscle mass indices (appendicular skeletal muscle mass (ASM) over height2(ASMIht), ASM/weight (ASMwt), ASM/body fat percentage (ASMbfp)and ASM/body mass index (BMI) ASMIbmi) with physical function and inflammation in pre-frail obese older adults. METHODS: Cross-sectional study of 407 community dwelling pre-frail older adults. Data on demographics, cognition, and physical function(gait speed, handgrip strength (HGS) and Short Physical Performance Battery (SPPB) test), body composition and inflammation biomarkers were collected. Participants were analysed based on BMI tertiles(T1 lowest,T3 highest). RESULTS: The mean age was 72.67 years, mean BMI 25.42 kg/m2 and 59.5 % were females. Participants in T3 had a mean BMI of 30.75 kg/m2, younger with lower education levels, multimorbidity, polypharmacy and lower prevalence of sarcopenia. In BMI T3, ASMIbmi was significantly associated with EQ-5D index (ß 0.53, 95 % CI 0.04 to 1.03, p = 0.033),HGS (ß 5.28, 95 % CI 0.27 to 10.29, p = 0.039), SPPB (ß 2.19, 95 % CI 0.47 to 3.91, p = 0.013) and IL-6 (ß -4.13, 95 % CI -7.46 to -0.81, p = 0.017). ASMIwt was associated with EQ-5D index (ß 0.17, 95 % CI 0.02 - 0.33, p = 0.047). ASMbfp was associated with HGS (ß 6.97, 95 % CI 0.051 to 13.92, p = 0.049). There was significant association of HGS with all muscle mass indices in BMI T2, and ASMbfpin BMI T1. CONCLUSION: ASMIbmi was significantly associated with SPPB, HGS, EQ-5D index and IL-6 in BMI T3. ASMbfp was associated with HGS in all the tertiles. Our results need further validation at population level.

Graft retrieval incisions in minimally invasive donor nephrectomy: Systematic review and network meta-analysis.

BACKGROUND: Various incisions are employed for graft extraction during minimally invasive donor nephrectomy, but an overarching synthesis of associated short-term donor outcomes is lacking. METHODS: An electronic literature search was conducted on PubMed, EMBASE and Scopus for studies comparing ≥2 graft extraction incisions in laparoscopic or robotic donor nephrectomy with ≥10 patients per arm. Eligible study designs included randomized trials, case-control, and cohort studies. Primary outcomes were donor length of stay (LOS); in-hospital analgesic requirement; and postoperative complications. Secondary outcomes were warm ischemia time (WIT), total operation time (TOT), and estimated blood loss (EBL). Random-effects Frequentist network meta-analyses were conducted for all outcomes. RESULTS: Twenty-nine studies (4702 patients) were shortlisted. Six incisions were analyzed: iliac, Pfannenstiel, midline hand-assisted laparoscopic (HAL), midline umbilical, flank and transvaginal natural orifice transluminal endoscopic surgery (NOTES). The flank incision had significantly longer LOS than all other incisions. LOS was significantly longer in Pfannenstiel than iliac incision (mean difference [MD] = 0.29, 95%CI = 0.002-0.58 days). Midline HAL had significantly shorter TOT than most other incisions. Midline umbilical incisions had significantly higher WIT than midline HAL and Pfannenstiel incisions. Midline HAL had shorter WIT than transvaginal NOTES (MD = 0.80, 95%CI = 0.05-1.56 min). No major differences were seen in analgesia requirement, postoperative complications and EBL. CONCLUSION: Six different incisions for graft retrieval are broadly comparable across most short-term outcomes although long-term outcomes remain to be elucidated. Iliac and Pfannenstiel incisions yielded similar outcomes besides marginally lower LOS for the former. Midline incision for HAL may be associated with shorter TOT, and transvaginal NOTES is an effective technique for selected female donors. TRIAL REGISTRATION: PROSPERO CRD42023445407.

Trends in surgical management of spinal metastases in a Singaporean tertiary referral center: a 17-year retrospective review.

Introduction: Surgical treatment is increasingly the treatment of choice in cancer patients with epidural spinal cord compression and spinal instability. There has also been an evolution in surgical treatment with the advent of minimally invasive surgical (MIS) techniques and separation surgery. This paper aims to investigate the changes in epidemiology, surgical technique, outcomes and complications in the last 17 years in a tertiary referral center in Singapore. Methods: This is a retrospective study of 383 patients with surgically treated spinal metastases treated between January 2005 to January 2022. Patients were divided into 3 groups, patients treated between 2005 - 2010, 2011-2016, and 2017- 2021. Demographic, oncological, surgical, patient outcome and survival data were collected. Statistical analysis with univariate analysis was performed to compare the groups. Results: There was an increase in surgical treatment (87 vs 105 vs 191). Lung, Breast and prostate cancer were the most common tumor types respectively. There was a significant increase in MIS(p<0.001) and Separation surgery (p<0.001). There was also a significant decrease in mean blood loss (1061ml vs 664 ml vs 594ml) (p<0.001) and total transfusion (562ml vs 349ml vs 239ml) (p<0.001). Group 3 patients were more likely to have improved or normal neurology (p=<0.001) and independent ambulatory status(p=0.012). There was no significant change in overall survival. Conclusion: There has been a significant change in our surgical practice with decreased blood loss, transfusion and improved neurological and functional outcomes. Patients should be managed in a multidisciplinary manner and surgical treatment should be recommended when indicated.

Outcomes and Complications of Surgery for Symptomatic Spinal Metastases; a Comparison Between Patients Aged ≥ 70 and <70.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: Physicians may be deterred from operating on elderly patients due to fears of poorer outcomes and complications. We aimed to compare the outcomes of surgical treatment of spinal metastases patients aged ≥70-yrs and <70-yrs. MATERIALS AND METHODS: This is a retrospective study of patients surgically treated for metastatic epidural spinal cord compression and spinal instability between January-2005 to December-2021. Follow-up was till death or minimum 1-year post-surgery. Outcomes included post-operative neurological status, ambulatory status, medical and surgical complications. Two Sample t-test/Mann Whitney U test were used for numerical variables and Pearson Chi-Squared or Fishers Exact test for categorical variables. Survival was presented with a Kaplan-Meier curve. P < .05 was significant. RESULTS: We identified 412 patients of which 29 (7.1%) patients were excluded due to loss to follow-up and previous surgical treatment. 79 (20.6%) were ≥70-yrs. Age ≥70-yrs patients had poorer ECOG scores (P = .0017) and Charlson Comorbidity Index (P < .001). No significant difference in modified Tokuhashi score (P = .393) was observed with significantly more ≥ prostate (P < .001) and liver (P = .029) cancer in ≥70-yrs. Improved or maintained normal neurological function (P = .934), independent ambulatory status (P = .171), and survival at 6 months (P = .119) and 12 months (P = .659) was not significantly different between both groups. Medical (P = .528) or surgical (P = .466) complication rates and readmission rates (P = .800) were similar. CONCLUSION: ≥70-yrs patients have comparable outcomes to <70-yr old patients with no significant increase in complication rates. Age should not be a determining factor in deciding surgical management of spinal metastases.

Indirect Treatment Comparison of First-Line CDK4/6-Inhibitors in Post-Menopausal Patients with HR+/HER2- Metastatic Breast Cancer.

Background: CDK4/6-inhibitors have demonstrated similar efficacy and are considered an effective first-line endocrine treatment of patients with hormone-receptor positive (HR+)/human-epidermal-growth-factor-receptor-2 negative (HER2-) metastatic breast cancer (MBC) in the endpoint of progression-free survival (PFS). Amongst these, palbociclib was first to achieve regulatory approval, followed subsequently by ribociclib and abemaciclib. However, recent updates of overall survival (OS) showed inconsistencies in the OS benefit for palbociclib compared with the other two CDK4/6-inhibitors. With the lack of head-to-head comparison studies, our study sought to compare indirect survival outcomes between CDK4/6-inhibitors in this setting using a novel reconstructive algorithm. Methods: Phase III randomized trials comparing first-line aromatase inhibitor with/without a CDK4/6-inhibitor in post-menopausal patients with HR+/HER2- MBC were identified through systemic review and literature search of online archives of published manuscripts and conference proceedings. A graphical reconstructive algorithm was utilized to retrieve time-to-event data from reported Kaplan-Meier OS and PFS plots to allow for comparison of survival outcomes. Survival analyses were conducted with Cox proportional-hazards model with a shared-frailty term. Results: Three randomized phase III trials-PALOMA-2, MONALEESA-2 and MONARCH-3-comprising 1827 patients were included. Indirect pairwise comparisons of all CDK4/6-inhibitors showed no significant PFS differences (all p > 0.05). Likewise, indirect treatment comparison between ribociclib vs. palbociclib (one-stage: HR = 0.903, 95%-CI: 0.746-1.094, p = 0.297), abemaciclib vs. palbociclib (one-stage: HR = 0.843, 95%-CI: 0.690-1.030, p = 0.094) and abemaciclib vs. ribociclib (one-stage: HR = 0.933, 95%-CI: 0.753-1.157, p = 0.528) failed to demonstrate a significant OS difference. Conclusions: Findings from this indirect treatment comparison suggest no significant PFS or OS differences between CDK4/6-inhibitors in post-menopausal patients with HR+/HER2- MBC.

Sublobar resection versus lobectomy for stage IA non-small-cell lung cancer ≤ 2 cm: a systematic review and patient-level meta-analysis.

Despite lobectomy being the standard of care for early-stage non-small-cell lung cancer (NSCLC), sublobar resection (segmentectomy or wedge resection) has recently been suggested to achieve similar outcomes. An electronic literature search was conducted to retrieve randomized controlled trials (RCTs) or propensity score-matched studies (PSMs) comparing lobectomy to sublobar resection in stage IA NSCLC ≤ 2 cm in size, with provision of Kaplan-Meier curves for overall survival (OS) and disease-free survival (DFS). A graphical reconstructive algorithm was used to obtain OS and DFS of individual patients, which was then pooled under random-effects individual patient data meta-analysis using Cox models to determine hazard ratios (HRs). Sensitivity analyses for OS and DFS were also performed, restricting to results from RCTs only. Seven studies (2528 patients) were retrieved. There were no significant differences in OS (shared-frailty HR = 0.92, 95% CI = 0.77-1.11, p = 0.378) or DFS (shared-frailty HR = 1.06, 95% CI = 0.90-1.24, p = 0.476) between lobectomy and sublobar resection. This comparison remained non-significant even when restricted to RCTs only. Pooled Kaplan-Meier curves of OS appeared to diverge over time, in favor of sublobar resection. This was confirmed on analysis of restricted mean survival time curves. This patient-level meta-analysis of high-quality studies demonstrates that sublobar resection is equivalent to lobectomy in patients with small stage IA NSCLC. Sublobar resection offers greater down-the-road benefits in patients who experience recurrence or a second primary tumor since the lung-sparing index surgery allows patients to receive further treatment safely. This heralds sublobar resection as the new standard of care in carefully selected early-stage patients.Trial registration: PROSPERO CRD42023385358.

Impact of exercise and leucine-enriched protein supplementation on physical function, body composition, and inflammation in pre-frail older adults: a quasi-experimental study.

Background: Exercise and a protein-enriched diet are essential for muscle protein synthesis, cellular growth, mitochondrial function, and immune function. The U.S. Food and Nutrition Board's current guideline on recommended dietary allowance for protein in older adults is 0.8 g/kg per day, which may not be sufficient in vulnerable pre-frail older adults. Aims: This study aimed to evaluate the impact of leucine-enriched protein supplementation with or without exercise over 3 months in pre-frail older adults who consumed ≤1 g/kg/day of protein on improving (i) physical function, (ii) body composition measures, and (iii) inflammatory biomarkers such as interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α). Methods: A non-randomized cluster quasi-experimental study guided by the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist of 178 pre-frail older adults [112 control, 44 nutrition (Nu), and 22 in the nutrition with exercise (Nu+Ex) group] comparing the effect of Nu+Ex and Nu on physical function, body composition, and inflammation. At 0, 3, and 6 months, questionnaires on demographics, depression, perceived health, and cognition were administered. Physical function assessment (short physical performance battery [SPPB] test, gait speed, handgrip strength, 5× sit-to-stand [STS]) was conducted, and body composition analysis was performed using a bioelectrical impedance analysis machine. IL-6 and TNF-α were measured at 0 and 3 months. Results: At 3 months, there were significant improvements in gait speed, 5× STS, SPPB scores, depression, perceived health, fat-free mass, and appendicular skeletal muscle mass indices in the Nu+Ex group. Both Nu+Ex and Nu groups had improvements in body cell mass and reductions in IL-6 and TNF-α. The improvements were not sustained after 6 months. Conclusion: Our study results need to be validated in future longitudinal randomized studies with a larger sample size focusing on populations at risk.

Smoke exposure and childhood atopic eczema and food allergy: A systematic review and meta-analysis.

BACKGROUND: There is no consensus on the effect of timing and type of smoke exposure on early allergy development. This study aimed to determine the relationship between early eczema or food allergy/hypersensitivity development in children by firstly investigating the effect of smoke exposure across critical development periods and secondly by analyzing effects of parental atcive or passive smoking. METHODS: Four databases (PubMed, Web of Science, Scopus and Embase) were searched in May 2022 and assessed by two independent reviewers. Case-control, cross-sectional or cohort studies reporting on smoke exposure from preconception to postnatal periods and atopic eczema, food allergy and/or hypersensitivity outcomes by age 3 years were included. The Newcastle-Ottawa Scale was used to assess study quality. Random effects model was used to estimate the pooled risk ratios. RESULTS: From 1689 identified records, 32 studies with nearly 190,000 subjects were included. Parental smoking during preconception, pregnancy and postnatal periods was generally not associated with the risk of eczema, food allergy and food sensitisation development by age 3 years. Maternal active smoking during pregnancy was negatively associated with self-reported doctor diagnosis of eczema (RR = 0.87, 95% CI 0.77-0.98; I2 = 50.56) and maternal passive smoking during pregnancy was positively associated with clinician assessment of eczema in one study (RR = 1.38; 95% CI 1.06-1.79). CONCLUSION: Our findings highlighted the importance of in utero programming in early-life allergy development. Despite the weak evidence, our results suggest pregnant women should minimise their contact with second-hand smoke to prevent offspring eczema development. There is a need for greater utilisation of objective allergy assessments in future studies.

Paediatric ventriculoperitoneal shunt failures: 12-year experience from a Singapore children's hospital.

PURPOSE: Cerebrospinal fluid (CSF) shunt failures in children are devastating. The primary aims of this study are to, firstly, review our institutional series of ventriculoperitoneal shunt (VPS) insertions and identify factors associated with shunt failure. METHODS: This is a single-institution, retrospective study conducted over a 12-year period. All patients under 18 years old with VPS inserted were included. Variables of interest such as patient characteristics, hydrocephalus aetiology, shunt implant details, and outcomes were subjected to statistical analyses. RESULTS: A total of 214 VPS patients were selected for this study. The mean age at VPS insertion was 6 months with a mean follow-up duration of 44 months. The most common type of hydrocephalus was obstructive (n = 142, 66.4%), and the most frequent aetiology was tumour-related (n = 66, 30.8%). The 30-day shunt failure rate was 9.3%: 9 infections (4.2%), 7 occlusions (3.3%), and 4 others (1.9%). After multivariable analysis, only recent central nervous system (CNS) infection prior to VPS insertion remained significant (OR 15.4 (1.3-175), p = 0.028). CONCLUSION: This is the first, large-scale local study focused on the shunt failure in Singaporean children. Significant findings in our study demonstrate that recently treated CNS infection is a factor associated with 30-day shunt failure while the values of CSF constituents were not contributory.

Anthracycline-Free Protocol for Favorable-Risk Childhood ALL: A Noninferiority Comparison Between Malaysia-Singapore ALL 2003 and ALL 2010 Studies.

PURPOSE: To investigate whether, for children with favorable-risk B-cell precursor ALL (BCP-ALL), an anthracycline-free protocol is noninferior to a modified Berlin-Frankfurt-Muenster ALL-IC2002 protocol, which includes 120 mg/m2 of anthracyclines. PATIENTS AND METHODS: Three hundred sixty-nine children with favorable-risk BCP-ALL (age 1-9 years, no extramedullary disease, and no high-risk genetics) who cleared minimal residual disease (≤0.01%) at the end of remission induction were enrolled into Ma-Spore (MS) ALL trials. One hundred sixty-seven standard-risk (SR) patients (34% of Malaysia-Singapore ALL 2003 study [MS2003]) were treated with the MS2003-SR protocol and received 120 mg/m2 of anthracyclines during delayed intensification while 202 patients (42% of MS2010) received an anthracycline-free successor protocol. The primary outcome was a noninferiority margin of 1.15 in 6-year event-free survival (EFS) between the MS2003-SR and MS2010-SR cohorts. RESULTS: The 6-year EFS of MS2003-SR and MS2010-SR (anthracycline-free) cohorts was 95.2% ± 1.7% and 96.5% ± 1.5%, respectively (P = .46). The corresponding 6-year overall survival was 97.6% and 99.0% ± 0.7% (P = .81), respectively. The cumulative incidence of relapse was 3.6% and 2.6%, respectively (P = .42). After adjustment for race, sex, age, presenting WBC, day 8 prednisolone response, and favorable genetic subgroups, the hazard ratio for MS2010-SR EFS was 0.98 (95% CI, 0.84 to 1.14; P = .79), confirming noninferiority. Compared with MS2003-SR, MS2010-SR had significantly lower episodes of bacteremia (30% v 45.6%; P = .04) and intensive care unit admissions (1.5% v 9.5%; P = .004). CONCLUSION: In comparison with MS2003-SR, the anthracycline-free MS2010-SR protocol is not inferior and was less toxic as treatment for favorable-risk childhood BCP-ALL.

Association of Motoric Cognitive Risk Syndrome with Sarcopenia and Systemic Inflammation in Pre-Frail Older Adults.

Motoric cognitive risk syndrome (MCR) is defined by the presence of slow gait and subjective cognitive decline. It is well recognized as a prodrome for dementia, but the biological mechanism and trajectory for MCR are still lacking. The objective of this study was to explore the association of MCR with body composition, including sarcopenia and systemic inflammation, in pre-frail older adults in a cross-sectional study of 397 pre-frail community-dwelling older adults. Data on demographics, physical function, frailty, cognition (Montreal Cognitive Assessment (MoCA)), perceived health and depression were collected. Body composition was measured using a bioelectrical impedance analyzer. Systemic inflammatory biomarkers, such as progranulin, growth differentiation factor-15 (GDF-15), interleukin-10 (IL-10), interleukin-6 and tumor necrosis factor-α (TNF-α), were collected. Univariate and multivariate logistic regression were used to analyze the association between MCR, body composition, sarcopenia and systemic inflammatory biomarkers. The prevalence of MCR was 14.9%. They were significantly older and there were more females, depression, functional impairment, lower education, physical activity and MoCA scores. Body fat percentage (BF%), fat mass index, fat to fat free mass ratio (FM/FFM) and sarcopenia prevalence were significantly higher in MCR. Serum GDF-15 and TNF-α levels were highest with progranulin/TNF-α and IL-10/TNF-α ratio lowest in MCR. Compared to healthy patients, MCR was significantly associated with sarcopenia (aOR 2.62; 95% CI 1.46-3.17), BF% (aOR 1.06; 95% CI 1.01-1.12), FMI (aOR 1.16; 95% CI 1.02-1.30) and FM/FFM (aOR 6.38; 95% CI 1.20-33.98). The association of IL-10 to TNF-α ratio (aOR 0.98, 95% CI 0.97-0.99) and IL-10 (aOR 2.22, 95% CI 0.05-0.98) with MCR were independent of sarcopenia and BF%. Longitudinal population studies are needed to understand the role of body fat indices and IL-10 in pre-frail older adults with MCR and trajectory to dementia.

Postsurgical outcomes of nonfunctioning pituitary adenomas: a patient-level meta-analysis.

BACKGROUND: Surgical resection is the main treatment for symptomatic nonfunctioning pituitary adenomas (NFPA). We aimed to analyze the impact of surgical approach, completeness of resection, and postoperative radiotherapy on long-term progression-free survival (PFS) of NFPA, using individual patient data (IPD) meta-analysis. METHODS: An electronic literature searched was conducted on PubMed, EMBASE, and Web of Science from database inception to 6 November 2022. Studies describing the natural history of surgically resected NFPA, with provision of Kaplan-Meier curves, were included. These were digitized to obtain IPD, which was pooled in one-stage and two-stage meta-analysis to determine hazard ratios (HRs) and 95%CIs of gross total resection (GTR) versus subtotal resection (STR), and postoperative radiotherapy versus none. An indirect analysis of single-arm data between endoscopic endonasal (EES) and microscopic transsphenoidal (MTS) surgical technique was also performed. RESULTS: Altogether, eleven studies (3941 patients) were retrieved. PFS was significantly lower in STR than GTR (shared-frailty HR 0.32, 95%CI 0.27-0.39, p < 0.001). Postoperative radiotherapy significantly improved PFS compared to no radiotherapy (shared-frailty HR 0.20, 95%CI 0.15-0.26, p < 0.001), including in the subgroup of patients with STR (shared-frailty HR 0.12, 95%CI 0.08-0.18, p < 0.001). Similar PFS was observed between EES and MTS (indirect HR 1.09, 95%CI 0.92-1.30, p = 0.301). CONCLUSIONS: This systematic review and patient-level meta-analysis provides a robust prognostication of surgically treated NFPA. We reinforce current guidelines stating that GTR should be the standard of surgical resection. Postoperative radiotherapy is of considerable benefit, especially for patients with STR. Surgical approach does not significantly affect long-term prognosis. REGISTRATION: PROSPERO CRD42022374034.

GDF-15 Is Associated with Poor Physical Function in Prefrail Older Adults with Diabetes.

Introduction: Growth differentiation factor 15 (GDF-15) has been shown to be a metabolic and appetite regulator in diabetes mellitus (DM) and obesity. We aimed to investigate (i) the association between GDF-15 and DM with and without poor physical function independent of inflammation and (ii) the prediction model for poor physical function in prefrail older adults. Methods: A cross-sectional study of 108-prefrail participants ≥60 years recruited for multidomain interventions. Data was collected for demographics, cognition, function, frailty, nutrition, handgrip strength (HGS), short physical performance battery (SPPB), and gait speed. Serum concentrations of GDF-15, IL-6, and TNF-α were measured. GDF-15 was classified into tertiles (T1, T2, and T3), and its association was studied with DM and physical function (DM poor physical function, DM no poor physical function, no DM poor physical function, and no DM no poor physical function). Results: Compared with T1, participants in T3 were significantly older, had a lower education level, had almost three times higher prevalence of DM, slower gait speed, longer chair-stand time, and lower SPPB scores. On multivariate analysis, the odds of having both DM and poor physical performance compared to having no DM and no poor physical performance were significantly higher in GDF-15 T3 vs. GDF-15 T1 (aOR 9.7, 95% CI 1.4-67.7; p = 0.021), and the odds of having DM no poor physical function compared to having no DM and no poor physical performance were significantly higher in GDF-15 T2 (aOR 12.7, 95% CI 1.1-143.7; p = 0.040) independent of BMI, IL-6, TNF-α, nutrition, physical function, education, age, and gender. Conclusion: The association of GDF-15 with DM-associated poor physical function is independent of inflammation in prefrail older adults. Its causal-association link needs to be determined in longitudinal studies.

Deep learning assessment compared to radiologist reporting for metastatic spinal cord compression on CT.

Introduction: Metastatic spinal cord compression (MSCC) is a disastrous complication of advanced malignancy. A deep learning (DL) algorithm for MSCC classification on CT could expedite timely diagnosis. In this study, we externally test a DL algorithm for MSCC classification on CT and compare with radiologist assessment. Methods: Retrospective collection of CT and corresponding MRI from patients with suspected MSCC was conducted from September 2007 to September 2020. Exclusion criteria were scans with instrumentation, no intravenous contrast, motion artefacts and non-thoracic coverage. Internal CT dataset split was 84% for training/validation and 16% for testing. An external test set was also utilised. Internal training/validation sets were labelled by radiologists with spine imaging specialization (6 and 11-years post-board certification) and were used to further develop a DL algorithm for MSCC classification. The spine imaging specialist (11-years expertise) labelled the test sets (reference standard). For evaluation of DL algorithm performance, internal and external test data were independently reviewed by four radiologists: two spine specialists (Rad1 and Rad2, 7 and 5-years post-board certification, respectively) and two oncological imaging specialists (Rad3 and Rad4, 3 and 5-years post-board certification, respectively). DL model performance was also compared against the CT report issued by the radiologist in a real clinical setting. Inter-rater agreement (Gwet's kappa) and sensitivity/specificity/AUCs were calculated. Results: Overall, 420 CT scans were evaluated (225 patients, mean age=60 ± 11.9[SD]); 354(84%) CTs for training/validation and 66(16%) CTs for internal testing. The DL algorithm showed high inter-rater agreement for three-class MSCC grading with kappas of 0.872 (p<0.001) and 0.844 (p<0.001) on internal and external testing, respectively. On internal testing DL algorithm inter-rater agreement (κ=0.872) was superior to Rad 2 (κ=0.795) and Rad 3 (κ=0.724) (both p<0.001). DL algorithm kappa of 0.844 on external testing was superior to Rad 3 (κ=0.721) (p<0.001). CT report classification of high-grade MSCC disease was poor with only slight inter-rater agreement (κ=0.027) and low sensitivity (44.0), relative to the DL algorithm with almost-perfect inter-rater agreement (κ=0.813) and high sensitivity (94.0) (p<0.001). Conclusion: Deep learning algorithm for metastatic spinal cord compression on CT showed superior performance to the CT report issued by experienced radiologists and could aid earlier diagnosis.

A deep learning-based technique for the diagnosis of epidural spinal cord compression on thoracolumbar CT.

PURPOSE: To develop a deep learning (DL) model for epidural spinal cord compression (ESCC) on CT, which will aid earlier ESCC diagnosis for less experienced clinicians. METHODS: We retrospectively collected CT and MRI data from adult patients with suspected ESCC at a tertiary referral institute from 2007 till 2020. A total of 183 patients were used for training/validation of the DL model. A separate test set of 40 patients was used for DL model evaluation and comprised 60 staging CT and matched MRI scans performed with an interval of up to 2 months. DL model performance was compared to eight readers: one musculoskeletal radiologist, two body radiologists, one spine surgeon, and four trainee spine surgeons. Diagnostic performance was evaluated using inter-rater agreement, sensitivity, specificity and AUC. RESULTS: Overall, 3115 axial CT slices were assessed. The DL model showed high kappa of 0.872 for normal, low and high-grade ESCC (trichotomous), which was superior compared to a body radiologist (R4, κ = 0.667) and all four trainee spine surgeons (κ range = 0.625-0.838)(all p < 0.001). In addition, for dichotomous normal versus any grade of ESCC detection, the DL model showed high kappa (κ = 0.879), sensitivity (91.82), specificity (92.01) and AUC (0.919), with the latter AUC superior to all readers (AUC range = 0.732-0.859, all p < 0.001). CONCLUSION: A deep learning model for the objective assessment of ESCC on CT had comparable or superior performance to radiologists and spine surgeons. Earlier diagnosis of ESCC on CT could reduce treatment delays, which are associated with poor outcomes, increased costs, and reduced survival.

Expansion sphincter pharyngoplasty in OSA: a 15 year review.

OBJECTIVE: A 15 year review of the outcomes and success rates of the Expansion Sphincter Pharyngoplasty (ESP) in the treatment of patients with obstructive sleep apnea (OSA). METHODS: A systemic review with two independent searches of MEDLINE, Google Scholar, Cochrane Library and Evidence-Based Medicine Reviews to identify publications relevant to OSA and Expansion Pharyngoplasty. All relevant studies published before 31 December 2021 were included. RESULTS: Sixteen studies were included in this strict systematic review with a total of 747 patients who had the ESP procedure were included. The mean age was 41.3 years, mean BMI 28.2, the mean pre-op AHI was 32.3 and post-op AHI was 10.0 (p < 0.05), the mean pre-op ESS was 11.4, had reduced to post-op 5.3 (p < 0.05), and the mean pre-op snore VAS decreased from 8.7 to 2.9 (p < 0.05), with a mean follow-up time of 9.5 months. The overall pooled success rate for all the 747 patients was 80.0%. There were no significant reported complications noted in these studies. CONCLUSION: After 15 years of presence, the expansion sphincter pharyngoplasty has shown to be reliably effective in the management of patients with OSA.

Factors associated with deep infiltrating endometriosis, adenomyosis and ovarian endometrioma.

INTRODUCTION: To compare epidemiological features and clinical presentations of deep infiltrating endometriosis with endometrioma and adenomyosis, as well as to identify risk factors for the respective histologically confirmed conditions. METHOD: Patients undergoing index surgery at the National University Hospital, Singapore for endometriosis or adenomyosis over a 7-year period-from 2015 to 2021-were identified from hospital databases using the Table of Surgical Procedures coding. Social and epidemiological features of cases with histologically confirmed diagnoses of endometrioma only, adenomyosis only, and deep infiltrating endometriosis were compared. Significant variables from univariate analysis were entered into 3 binary multivariate logistic regression models to obtain independent risk factors for: deep infiltrating endometriosis versus endometrioma only, deep infiltrating endometriosis versus adenomyosis only, and adenomyosis only versus endometrioma only. RESULTS: A total of 258 patients were included with 59 ovarian endometrioma only, 47 adenomyosis only, and 152 deep infiltrating endometrioses. Compared to endometrioma only, deep infiltrating endometriosis was associated with higher rates of severe dysmenorrhoea (odds ratio [OR] 2.80, 95% confidence interval [CI] 1.02-7.70) and out-of-pocket private surgical care (OR 4.72, 95% CI 1.85-12.04). Compared to adenomyosis only, deep infiltrating endometriosis was associated with a higher fertility desire (OR 13.47, 95% CI 1.01-180.59) and a lower body mass index (OR 0.89, 95% CI 0.79-0.99). In contrast, heavy menstrual bleeding was the hallmark of adenomyosis, being less common in patients with endometriosis. CONCLUSION: Deep infiltrating endometriosis is associated with severe dysmenorrhoea, pain related to urinary and gastrointestinal tracts, higher fertility desire and infertility rate. Patients with pain symptomatology and subfertility should be referred early to a tertiary centre with the capability to diagnose and manage deep infiltrating endometriosis.