Effect of Preoperative Very Low-Calorie Diets on Hepatic Steatosis, Fibrosis, and Perioperative Outcomes of Bariatric Surgery.

Introduction: Preoperative weight loss through a very low-calorie diet (VLCD) has been shown to reduce liver volume and technical difficulty in patients undergoing metabolic and bariatric surgery (MBS). However, the effect of preoperative VLCD on liver histology and other outcomes is not well demonstrated. Our study aimed to explore the effect of a 2-week preoperative VLCD, compared with no-dietary intervention, on hepatic steatosis, fibrosis, weight loss, and other postoperative outcomes of MBS. Materials and Methods: This retrospective study was conducted at the Chulalongkorn Bariatric and Metabolic Institute, King Chulalongkorn Memorial Hospital, Bangkok, Thailand. The medical records of patients with severe obesity (body mass index ≥50 kg/m2) attending the clinic from January 2005 to December 2020 were reviewed. Clinical data and laboratory investigations were collected at baseline and at each follow-up visit, up to 5 years postoperatively. Hepatic steatosis and fibrosis were assessed by liver biopsy intraoperatively. Results: A total of 181 patients were included in this study. Preoperative VLCD was prescribed in 65 patients (VLCD group) and 116 patients received their usual diet (control group). Mean preoperative weight loss was 9.1 ± 6.1 kg in the VLCD group versus 0.0 ± 0.0 kg in the control group (P = .000). The VLCD group had significantly less number of patients with moderate and severe liver steatosis from the liver biopsy specimens (16.2% versus 46.3%; P = .008). However, there was no significant difference in fibrosis grade between those with VLCD and control (≥F2-fibrosis; 2.7% versus 7.5%; P = .118). Moreover, preoperative VLCD could reduce operating time in patients who underwent both laparoscopic Roux-en-Y gastric bypass (LRYGB; VLCD 163.4 ± 38.2 minutes versus control 215.1 ± 67.4 minute, P = .000) and laparoscopic sleeve gastrectomy (LSG; VLCD 110.8 ± 20.0 minutes versus control 131.0 ± 38.1 minutes, P = .004). During the 5-year follow-up, there were a significant difference of HbA1C between the VLCD and the control group (coefficient: -0.24 with 95% confidence interval [CI]: -0.44 to -0.04, P = .019), particularly in patients who underwent LRYGB (Coefficient: -0.26 with 95% CI: -0.49 to -0.03, P = .028), but not LSG. However, long-term weight loss outcomes and other biochemical outcomes were not different between the VLCD and the control group. Conclusion: Preoperative VLCD was associated with reduced liver steatosis and operative time in patients who underwent LRYGB and LSG. Moreover, preoperative VLCD significantly decreased HbA1C during a 5-year follow-up period. Therefore, it should be considered in patients with severe obesity, who will undergo MBS.

Which approach of total hip arthroplasty is the best efficacy and least complication?

BACKGROUND: Total hip arthroplasty is as an effective intervention to relieve pain and improve hip function. Approaches of the hip have been exhaustively explored about pros and cons. The efficacy and the complications of hip approaches remains inconclusive. This study conducted an umbrella review to systematically appraise previous meta-analysis (MAs) including conventional posterior approach (PA), and minimally invasive surgeries as the lateral approach (LA), direct anterior approach (DAA), 2-incisions method, mini-lateral approach and the newest technique direct superior approach (DSA) or supercapsular percutaneously-assisted total hip (SuperPath). AIM: To compare the efficacy and complications of hip approaches that have been published in all MAs and randomized controlled trials (RCTs). METHODS: MAs were identified from MEDLINE and Scopus from inception until 2023. RCTs were then updated from the latest MA to September 2023. This study included studies which compared hip approaches and reported at least one outcome such as Harris Hip Score (HHS), dislocation, intra-operative fracture, wound complication, nerve injury, operative time, operative blood loss, length of hospital stay, incision length and VAS pain. Data were independently selected, extracted and assessed by two reviewers. Network MA and cluster rank and surface under the cumulative ranking curve (SUCRA) were estimated for treatment efficacy and safety. RESULTS: Finally, twenty-eight MAs (40 RCTs), and 13 RCTs were retrieved. In total 47 RCTs were included for reanalysis. The results of corrected covered area showed high degree (13.80%). Among 47 RCTs, most of the studies were low risk of bias in part of random process and outcome reporting, while other domains were medium to high risk of bias. DAA significantly provided higher HHS at three months than PA [pooled unstandardized mean difference (USMD): 3.49, 95% confidence interval (CI): 0.98, 6.00 with SUCRA: 85.9], followed by DSA/SuperPath (USMD: 1.57, 95%CI: -1.55, 4.69 with SUCRA: 57.6). All approaches had indifferent dislocation and intraoperative fracture rates. SUCRA comparing early functional outcome and composite complications (dislocation, intra-operative fracture, wound complication, and nerve injury) found DAA was the best approach followed by DSA/SuperPath. CONCLUSION: DSA/SuperPath had better earlier functional outcome than PA, but still could not overcome the result of DAA. This technique might be the other preferred option with acceptable complications.

Impact of coronary CT angiography in selection of treatment modalities and subsequent cardiovascular events in Thai patients with stable CAD.

BACKGROUND: Coronary computed tomography angiography (CCTA) enables improved diagnosis of subclinical, coronary artery disease (CAD). This retrospective cohort study investigated the association between different treatment modalities guided by CCTA and the prevention of major adverse cardiovascular events (MACEs) in patients with stable CAD. METHODS: From 2005 to 2013, a total of 9338 patients, including both asymptomatic individuals with risk factors and symptomatic patients with suspected CAD, who underwent CCTA were analyzed. The patients were categorized into one of three groups based on results of CCTA: obstructive CAD (≥ 50% stenosis in at least one vessel), non-obstructive CAD (1-49% stenosis in at least one vessel), and no observed CAD (0% stenosis). They were subsequently followed up to assess the treatment they received and the occurrence of MACEs (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or late revascularization). RESULTS: During an average follow-up period of 9.9 ± 2.4 years, patients with obstructive CAD had the highest incidence of MACEs (19.8%), followed by those with non-obstructive CAD and no coronary artery stenosis (10.3 and 5.5%, respectively). After adjusting for confounding variables, it was found that patients treated with statins alone were the least likely to develop MACEs in all three groups, compared to those receiving no treatment, with hazard ratios (95% CI) of 0.43 (0.32, 0.58), 0.47 (0.34, 0.64), and 0.46 (0.31, 0.69), respectively. In patients with obstructive CAD, treatment with a combination of statin and aspirin, or early revascularization was associated with a lower likelihood of experiencing MACEs compared to no treatment with hazard ratios of 0.43 (0.33, 0.58) and 0.64 (0.43, 0.97), respectively. CONCLUSION: CCTA offers useful guidance for the treatment of patients with stable CAD and shows potential for prevention of CV events. However, the full validation of a given strategy utilizing CCTA will require a prospective longitudinal study, utilizing a randomized clinical trial design.

Efficacy of Treatment for Metastatic Hormone-Sensitive Prostate Cancer: An Umbrella Review of Systematic Reviews and Meta-Analyses.

PURPOSE: This umbrella review focused on evaluating the efficacy and adverse events of the metastatic hormone-sensitive prostate cancer patients receiving any treatment regimens, including ADT alone or combination treatments. METHODS: This study conducted an umbrella review following the PRISMA 2020 checklist, aiming to summarize the available studies to evaluate the efficacy of medical treatments for metastatic hormone-sensitive prostate cancer. A literature search was performed to identify systematic reviews and meta-analyses (SRMAs) that included only randomized controlled trials (RCTs) up to September 2023. This study summarized their findings, evaluated overlapping data (i.e., the same RCTs were included in >one SRMA), tested for excessive significance (i.e., observed number of statistically significant studies > expected number by chance) and assessed the quality of the studies. RESULTS: A total of 4191 studies were identified, but only 27 were included. Among those 27 studies, 12 were network meta-analyses and 15 were direct meta-analyses. Most studies showed no statistically significant difference in overall mortality among GnRH agonists, antagonists and bilateral orchiectomy. Combination treatment is more beneficial than ADT alone in both OS and PFS outcomes with more adverse events. Nevertheless, there is no OS advantage of any combination regimen over the others. CONCLUSION: Combination treatments demonstrated clear benefits in OS and PFS over ADT alone with more AEs. Further studies are needed to compare among combination treatments.

A clinical prediction model to differentiate tuberculous spondylodiscitis from pyogenic spontaneous spondylodiscitis.

BACKGROUND: Microbiological diagnosis of tuberculous spondylodiscitis (TS) and pyogenic spontaneous spondylodiscitis (PS) is sometime difficult. This study aimed to identify the predictive factors for differentiating TS from PS using clinical characteristics, radiologic findings, and biomarkers, and to develop scoring system by using predictive factors to stratify the probability of TS. METHODS: A retrospective single-center study. Demographics, clinical characteristics, laboratory findings and radiographic findings of patients, confirmed causative pathogens of PS or TS, were assessed for independent factors that associated with TS. The coefficients and odds ratio (OR) of the final model were estimated and used to construct the scoring scheme to identify patients with TS. RESULTS: There were 73 patients (51.8%) with TS and 68 patients (48.2%) with PS. TS was more frequently associated with younger age, history of tuberculous infection, longer duration of symptoms, no fever, thoracic spine involvement, ≥3 vertebrae involvement, presence of paraspinal abscess in magnetic-resonance-image (MRI), well-defined thin wall abscess, anterior subligamentous abscess, and lower biomarker levels included white blood cell (WBC) counts, erythrocyte-sedimentation-rate (ESR), neutrophil fraction, and C-reactive protein (all p < 0.05). Multivariate logistic regression analysis revealed significant predictors of TS included WBC ≤9,700/mm3 (odds ratio [OR] 13.11, 95% confidence interval [CI] 4.23-40.61), neutrophil fraction ≤78% (OR 4.93, 95% CI 1.59-15.30), ESR ≤92 mm/hr (OR 4.07, 95% CI 1.24-13.36) and presence of paraspinal abscess in MRI (OR 10.25, 95% CI 3.17-33.13), with an area under the curve of 0.921. The scoring system stratified the probability of TS into three categories: low, moderate, and high with a TS prevalence of 8.1%, 29.6%, and 82.2%, respectively. CONCLUSIONS: This prediction model incorporating WBC, neutrophil fraction counts, ESR and presence of paraspinal abscess accurately predicted the causative pathogens. The scoring scheme with combination of these biomarkers and radiologic features can be useful to differentiate TS from PS.

Treatment of obstructive sleep apnea in high risk pregnancy: a multicenter randomized controlled trial.

BACKGROUND: Obstructive sleep apnea (OSA) during pregnancy is a risk factor for preeclampsia possibly through a link to placental physiology. This study evaluates the efficacy of continuous positive airway pressure (CPAP) on the modulation of blood pressure and the reduction in preeclampsia in women with high-risk pregnancy and OSA. METHODS: A multicenter open-label, randomized controlled trial comparing CPAP treatment versus usual antenatal care was conducted in three academic hospitals in Bangkok, Thailand. Participants included singleton pregnant women aged older than 18 years with any high-risk condition (i.e., chronic hypertension, obesity, history of preeclampsia or gestational diabetes in the previous pregnancy, or diabetes), and OSA (respiratory disturbance index 5-29.99 events/hour by polysomnography), who presented either in the first trimester (gestational age, GA 0-16 weeks) or subsequently developed OSA during the 2nd trimester (GA 24-28 weeks). The primary endpoint was blood pressure during antenatal care. Secondary endpoints included the incidence of preeclampsia. An intention-to-treat analysis was performed with additional per-protocol and counterfactual analyses for handling of nonadherence. RESULTS: Of 340 participants, 96.5% were recruited during the first trimester. Thirty participants were later excluded leaving 153 and 157 participants in the CPAP and usual-care groups for the modified-intention-to-treat analysis. CPAP adherence rate was 32.7% with average use of 2.5 h/night. Overall, CPAP treatment significantly lowered diastolic blood pressure (DBP) by - 2.2 mmHg [95% CI (- 3.9, - 0.4), p = 0.014], representing approximately - 0.5 mmHg per hour of CPAP use [95%CI (- 0.89, - 0.10), p = 0.013]. CPAP treatment also altered the blood pressure trajectory by continuously lowering DBP throughout pregnancy with mean differences (95% CI) of - 3.09 (- 5.34, - 0.93), - 3.49 (- 5.67, - 1.31) and - 3.03 (- 5.20, - 0.85) mmHg at GA 18-20, 24-28, and 32-34 weeks, respectively compared to 0-16 weeks. Preeclampsia rate was 13.1% (20/153 participants) in the CPAP and 22.3% (35/157 participants) in the usual-care group with a risk difference (95% CI) of - 9% (- 18%, - 1%, p-value = 0.032) and a number-needed-to-treat (95% CI) of 11 (1, 21). CONCLUSIONS: CPAP treatment in women with even mild-to-moderate OSA and high-risk pregnancy demonstrated reductions in both DBP and the incidence of preeclampsia. CPAP treatment also demonstrated a sustained reduction in DBP throughout gestation. Trial registration ClinicalTrial.GovNCT03356106, retrospectively registered November 29, 2017.

Is anti-seizure medication the culprit of SUDEP?

BACKGROUND: Heart rate variability (HRV) reduction is a potential biomarker for sudden cardiac death. This study aimed to study the effects of anti-seizure medications (ASMs), adjusted with reported factors associated with sudden unexpected death in epilepsy (SUDEP) on HRV parameters. METHODS: We recruited patients who were admitted in our epilepsy monitoring unit between January 2013 and December 2021. Two 5-min electrocardiogram epochs during wakefulness and sleep were selected in each patient. HRV analysis with Python® software was performed. The imputed datasets were used for linear regression analysis to assess association between each ASM item and all HRV parameters. The effects of ASM on HRV parameters were subsequently adjusted with the significant clinical characteristics and the concomitant use of other ASMs, respectively. RESULTS: Carbamazepine (CBZ), levetiracetam (LEV), lamotrigine (LTG), and clonazepam (CZP) were statistically significantly associated with changes of sleep HRV parameters. Only CBZ showed negative effects with reduction in HRV, evidenced as lower standard deviation of RR interval (SDNN), even when adjusted with concomitant use of other ASMs (p = 0.045) and had a trend of significance when adjusted with significant clinical characteristics of concurrent taking of beta-blocker drug (p = 0.052). LEV and CZP showed opposite effects with increased HRV even when adjusted with significant clinical characteristics and the concomitant use of other ASMs. CONCLUSIONS: CBZ showed negative effects on HRV. We proposed that CBZ should be cautiously used in patients with known risks for SUDEP. In addition, HRV assessment should be performed prior to commencing CBZ and re-performed in follow-up in cases of prolonged use.

Parental Awareness, Knowledge, and Attitudes Regarding Current and Future Newborn Bloodspot Screening: The First Report from Thailand.

Newborn screening (NBS) is a public health service that is used to screen for treatable conditions in many countries, including Thailand. Several reports have revealed low levels of parental awareness and knowledge about NBS. Because of limited data on parental perspectives toward NBS in Asia and the differences in socio-cultural and economic contexts between Western and Asian countries, we conducted a study to explore parental perspectives on NBS in Thailand. A Thai questionnaire to assess awareness, knowledge, and attitudes regarding NBS was constructed. The final questionnaire was distributed to pregnant women, with or without their spouses, and to parents of children aged up to one year who visited the study sites in 2022. A total of 717 participants were enrolled. Up to 60% of parents were identified as having good awareness, which was significantly associated with gender, age, and occupation. Only 10% of parents were classified as having good knowledge relative to their education level and occupation. Providing appropriate NBS education should be initiated during antenatal care, focusing on both parents. This study noted a positive attitude toward expanded NBS for treatable inborn metabolic diseases, incurable disorders, and adult-onset diseases. However, modernized NBS should be holistically evaluated by multiple stakeholders in each country because of different socio-cultural and economic contexts.

Platelet-rich plasma injection for the treatment of ankle osteoarthritis: a systematic review and meta-analysis.

BACKGROUND: Platelet-rich plasma (PRP) injection for ankle osteoarthritis (OA) treatment showed contradictory results. This review was aimed to pool individual studies which assessed the efficacy of PRP for ankle OA treatment. METHODS: This study was conducted following the preferred report items of systematic review and meta-analysis guideline. PubMed and Scopus were searched up to January 2023. Meta-analysis, or individual randomised controlled trial (RCT), or observational studies were included if they involved ankle OA with aged ≥ 18 years, compared before-after receiving PRP, or PRP with other treatments, and reported visual analog scale (VAS) or functional outcomes. Selection of eligible studies and data extraction were independently performed by two authors. Heterogeneity test using Cochrane Q test and the I2-statistic were assessed. Standardised (SMD) or unstandardised mean difference (USMD) and 95% confidence interval (CI) were estimated and pooled across studies. RESULTS: Three studies from meta-analysis and two individual studies were included, which consisted of one RCT and four before-after studies with 184 ankle OAs and 132 PRP. The average age was 50.8-59.3 years, and 25-60% of PRP injected cases were male. The number of primary ankle OA was accounted to 0-100%. When compared to before treatment, PRP significantly reduced VAS and functional score at 12 weeks with pooled USMD of - 2.80, 95% CI - 3.91, - 2.68; p < 0.001 (Q = 82.91, p < 0.001; I2 96.38%), and pooled SMD of 1.73, 95% CI 1.37, 2.09; p < 0.001 (Q = 4.87, p = 0.18; I2 38.44%), respectively. CONCLUSION: PRP may beneficially improve pain and functional scores for ankle OA in a short-term period. Its magnitude of improvement seems to be similar to placebo effects from the previous RCT. A large-scale RCT with proper whole blood and PRP preparation processes is required to prove treatment effects. Trial registration PROSPERO number CRD42022297503.

Comparison of diagnostic accuracy for diabetes diagnosis: A systematic review and network meta-analysis.

Aim: Fasting Plasma Glucose (FPG) and Hemoglobin A1c (HbA1c) are used as diagnostic tests for diagnosing diabetes mellitus, but it is unclear which test has the best diagnostic accuracy. This systematic review and network meta-analysis aimed to estimate the diagnostic accuracy of HbA1c ≥ 6.5%, FPG ≥ 126 mg/dl, and the combination of HbA1c ≥ 6.5% or FPG ≥ 126 mg/dl (HbA1c| FPG), compared with Oral Glucose Tolerance Test (OGTT) ≥ 200 mg/dl for diagnosis diabetes. Materials and methods: We performed a comprehensive search in PubMed, Embase, Cochrane Library, and Scopus from inception to September 24th, 2021. Inclusion criteria were any study design comparing HbA1c ≥ 6.5%, FPG ≥ 126 mg/dl, and HbA1c ≥ 6.5% or FPG ≥ 126 mg/dl with OGTT ≥ 200 mg/dl as the reference test. Data were independently extracted, risk of bias was assessed using QUADAS-2 by two reviewers. Network meta-analysis was done using a bivariate regression model using the Bayesian framework. The relative ranking of all tests was also assessed. Results: Out of 5,026 studies, 73 were included. The sensitivities of HbA1c, FPG, and HbA1c| FPG were 0.51 [95% Credible Interval (CrI): 0.43, 0.58], 0.49 (95% CrI: 0.43, 0.55), and 0.64 (95% CrI: 0.51, 0.75), while the specificities were 0.96 (95% CrI: 0.94, 0.97), 0.98 (95% CrI: 0.97, 0.98), and 0.95 (95% CrI: 0.88, 0.98), respectively. The corresponding positive likelihood ratios (LR) were 13.36 (95% CrI: 8.91, 20.72), 21.94 (95% CrI: 15.04, 31.88), and 11.78 (95% CrI: 5.48, 26.56). HbA1c| FPG is superior based on sensitivity, whereas FPG is ranked best based on specificity and positive LR. Conclusion: Our findings suggest that FPG ≥ 126 mg/dl should be recommended as the best diagnostic test for diabetes. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42021282856.

The efficacy of gait rehabilitations for the treatment of incomplete spinal cord injury: a systematic review and network meta-analysis.

BACKGROUND: Recent pieces of evidence about the efficacy of gait rehabilitation for incomplete spinal cord injury remain unclear. We aimed to estimate the treatment effect and find the best gait rehabilitation to regain velocity, distance, and Walking Index Spinal Cord Injury (WISCI) among incomplete spinal cord injury patients. METHOD: PubMed and Scopus databases were searched from inception to October 2022. Randomized controlled trials (RCTs) were included in comparison with any of the following: conventional physical therapy, treadmill, functional electrical stimulation and robotic-assisted gait training, and reported at least one outcome. Two reviewers independently selected the studies and extracted the data. Meta-analysis was performed using random-effects or fixed-effect model according to the heterogeneity. Network meta-analysis (NMA) was indirectly compared with all interventions and reported as pooled unstandardized mean difference (USMD) and 95% confidence interval (CI). Surface under the cumulative ranking curve (SUCRA) was calculated to identify the best intervention. RESULTS: We included 17 RCTs (709 participants) with the mean age of 43.9 years. Acute-phase robotic-assisted gait training significantly improved the velocity (USMD 0.1 m/s, 95% CI 0.05, 0.14), distance (USMD 64.75 m, 95% CI 27.24, 102.27), and WISCI (USMD 3.28, 95% CI 0.12, 6.45) compared to conventional physical therapy. In NMA, functional electrical stimulation had the highest probability of being the best intervention for velocity (66.6%, SUCRA 82.1) and distance (39.7%, SUCRA 67.4), followed by treadmill, functional electrical stimulation plus treadmill, robotic-assisted gait training, and conventional physical therapy, respectively. CONCLUSION: Functional electrical stimulation seems to be the best treatment to improve walking velocity and distance for incomplete spinal cord injury patients. However, a large-scale RCT is required to study the adverse events of these interventions. TRIAL REGISTRATION: PROSPERO number CRD42019145797.

Validity of Simple Self-Reported Periodontal Status Questions.

OBJECTIVE: The aim of this research was to evaluate the validity of the questions developed by Thai periodontists on self-reported periodontal status and symptoms in identifying severe periodontitis amongst adults in Thailand. METHODS: Registered Electricity Generating Authority of Thailand (EGAT) employees completed medical examinations and full-mouth periodontal examinations. They also were interviewed using a self-reported questionnaire that was developed by Thai periodontists. The questions pertained to their periodontal status and symptoms comprising swollen gums, bad breath, loose teeth, bleeding on brushing, painful gums, and pus or abscesses. The participants were categorised as having nonsevere and severe periodontitis according to the Centers for Disease Control and Prevention in partnership with the American Academy of Periodontology (CDC/AAP) case definitions. Self-reported periodontal status and symptom results were compared with actual periodontal status. The area under the receiver operating characteristic curve (AUROCC), sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated. RESULTS: A total of 1393 EGAT employees participated in this study. The questions on self-reported periodontal status and all symptoms poorly identified patients with severe periodontitis, with an AUROCC of 0.52 to 0.60. The sensitivity was 5.0% to 40.2%; however, the specificity was good, at 73.2% to 99.1%. The validity of the self-reported questions was comparable amongst the sex, education, and income subgroups. CONCLUSIONS: This study demonstrated that self-reported periodontal status and symptoms were inadequate in identifying patients with severe periodontal disease.

Treatment outcomes of advanced hepatocellular carcinoma in real-life practice: Chemotherapy versus multikinase inhibitors.

BACKGROUND: Multikinase inhibitors (MKIs) represent the main treatment options for advanced hepatocellular carcinoma (aHCC). However, accessibility in developing countries is limited. A chemotherapy, Fluorouracil and Oxaliplatin (FOLFOX), offers a less expensive treatment. Therefore, this study sought to compare the clinical effectiveness of FOLFOX with Sorafenib as a first-line treatment for aHCC in real-life practice. METHODS: A retrospective aHCC cohort from four Thai hospitals was investigated for patients who received FOLFOX or Sorafenib between 2013-2019. Multiple imputation by chained equations addressed missing covariate data in a treatment effect model using Weight-adjusted-censoring inverse-probability-weighted regression adjustment; overall survival (OS) and progression-free survival (PFS) were estimated. RESULTS: A total of 504 patients were included, (Sorafenib [n = 382] and FOLFOX [n = 122]). The treatment effect model estimated a median OS for Sorafenib and FOLFOX of 11.38 and 8.22 months, representing a significantly shorter OS (95% confidence interval) of -3.16 (-6.21, -0.11) months for FOLFOX, p = 0.042. A significant shorter median PFS of FOLFOX to Sorafenib of -2.13 (-3.03, -1.24) months, p < 0.001, was reported. CONCLUSION: Despite significantly shorter median OS and PFS than Sorafenib, FOLFOX still extended OS by 8.22 months. This evidence may offer clinical utility to physicians considering treatment options for aHCC in low resource settings.

Association of zinc deficiency with infectious complications in pediatric hematopoietic stem cell transplantation patients.

BACKGROUND: Zinc plays essential roles in immune function and epithelial integrity. Patients undergoing hematopoietic stem cell transplantation (HSCT) often have low plasma zinc levels because of poor intake and diarrhea. We hypothesized that patients with zinc deficiency before HSCT had worse infectious complications after HSCT compared with patients with normal zinc levels. Citrulline, a marker of intestinal integrity, was also hypothesized to be lower in patients with zinc deficiency. PATIENTS AND METHODS: Thirty patients undergoing HSCT at Ramathibodi Hospital during March 2020-September 2021 were enrolled. Blood samples for plasma zinc and citrulline were collected during the HSCT period. The 14- and 90-day outcomes after HSCT were prospectively recorded. RESULTS: Twelve of 30 (40%) patients had zinc deficiency before HSCT. Zinc-deficient patients were younger (median (interquartile range): 6 (8.8) vs 13 (5.8) years old; p = 0.017). Zinc levels tended to increase after admission in both groups. Patients with zinc deficiency had lower citrulline levels than those with normal zinc levels. Citrulline levels decreased in both groups after stem cell infusion, and the level was not significantly different between the two groups. Zinc-deficient patients had a higher rate of bacterial infection within 90 days after HSCT than those with normal zinc levels (6 in 12 patients (50.0%) vs 1 in 18 patients (5.6%); odds ratio [OR]: 17.0; 95% confidence interval [CI]: 1.68-171.70; p = 0.016). This remained significant after adjustments for age (adjusted OR: 12.31; 95% CI: 1.084-139.92; p = 0.043). CONCLUSION: The prevalence of zinc deficiency in pediatric patients undergoing HSCT was high. Zinc-deficient patients had lower citrulline levels and higher incidence of bacterial infection after HSCT. However, citrulline level was not different between patients with and without bacterial infections. It is worth to investigate whether zinc supplementation before HSCT can reduce bacterial infection after HSCT.

Efficacy of conservative treatment for spastic cerebral palsy children with equinus gait: a systematic review and meta-analysis.

BACKGROUND: Comparisons between various conservative managements of spastic equinus deformity in cerebral palsy demonstrated limited evidences, to evaluate the efficacy of conservative treatment among cerebral palsy children with spastic equinus foot regarding gait and ankle motion. METHODS: Studies were identified from PubMed and Scopus up to February 2022. Inclusion criteria were randomized controlled trial (RCT), conducted in spastic cerebral palsy children with equinus deformity, aged less than 18 years, compared any conservative treatments (Botulinum toxin A; BoNT-A, casting, physical therapy, and orthosis), and evaluated gait improvement (Physician Rating Scale or Video Gait Analysis), Observational Gait Scale, Clinical Gait Assessment Score, ankle dorsiflexion (ankle dorsiflexion at initial contact, and passive ankle dorsiflexion), or Gross Motor Function Measure. Any study with the participants who recently underwent surgery or received BoNT-A or insufficient data was excluded. Two authors were independently selected and extracted data. Risk of bias was assessed using a revised Cochrane risk-of-bias tool for randomized trials. I2 was performed to evaluate heterogeneity. Risk ratio (RR), the unstandardized mean difference (USMD), and the standardized mean difference were used to estimate treatment effects with 95% confidence interval (CI). RESULTS: From 20 included studies (716 children), 15 RCTs were eligible for meta-analysis (35% had low risk of bias). BoNT-A had higher number of gait improvements than placebo (RR 2.64, 95% CI 1.71, 4.07, I2 = 0). Its combination with physical therapy yielded better passive ankle dorsiflexion at knee extension than physical therapy alone (USMD = 4.16 degrees; 95% CI 1.54, 6.78, I2 = 36%). Casting with or without BoNT-A had no different gait improvement and ankle dorsiflexion at knee extension when compared to BoNT-A. Orthosis significantly increased ankle dorsiflexion at initial contact comparing to control (USMD 10.22 degrees, 95 CI% 5.13, 15.31, I2 = 87%). CONCLUSION: BoNT-A and casting contribute to gait improvement and ankle dorsiflexion at knee extension. BoNT-A specifically provided gait improvement over the placebo and additive effect to physical therapy for passive ankle dorsiflexion. Orthosis would be useful for ankle dorsiflexion at initial contact. Trial registration PROSPERO number CRD42019146373.

Comparison of doses and injection sites of botulinum toxin for chronic anal fissure: A systematic review and network meta-analysis of randomized controlled trials.

BACKGROUND: There are no consensus guidelines on the optimal dose or injection site of botulinum toxin (BT) for chronic anal fissure (CAF). The objective of this study was to determine the appropriate dose and injection site of BT for CAF by comparing healing rate and adverse effects (incontinence and recurrence). METHODS: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL) and Scopus were searched from inception through May 31, 2021. Randomized controlled trials evaluating healing and adverse effects of BT injection for CAF published in any language were selected. Multiple treatment comparisons and ranking were performed using a two-stage network meta-analysis, and results were graded by Confidence in Network Meta-Analysis tool. RESULTS: Twenty-seven trials involving 1880 patients were included. The results demonstrated that high-dose-BT had significantly higher short-term healing when injected out of the fissure (OF) site than each side of the fissure (SF) site, with a risk ratio (RR) of 2.12 (1.08, 4.15); low-dose-BT did not show any difference across OF and SF site with RR of 1.20 (0.85, 1.68). High-dose-BT at the OF site showed similar healing to low-dose-BT at the same site (RR of 1.02 (0.79, 1.31)) but with a higher risk of incontinence with RR of 3.54 (0.85, 14.76). In contrast, high-dose-BT at the SF site showed lower healing compared to low-dose-BT at the same site with RR of 0.57 (0.29, 1.14). Both high-dose-BT and low-dose-BT at the OF site had higher recurrence than high-dose-BT or low-dose-BT at the SF site with RR of 2.08 (0.33, 13.11) and 1.89 (0.60, 5.94), respectively. CONCLUSIONS: Given moderate level of evidence, low-dose BT is optimal; injection out of the fissure site improves short-term outcomes while injection each side of the fissure site tends to reduce recurrence in the longer term.

Causal Relationship of Coronary Artery Calcium on Myocardial Infarction and Preventive Effect of Antiplatelet Therapy.

Background: The role of coronary artery calcium score (CACS) to guide antiplatelet therapy in order to prevent myocardial infarction (MI) is still uncertain. This study aimed to find the causal relationship of CACS on MI and preventive effect of antiplatelet therapy. Methods: From 2005 to 2013, all patients with cardiovascular risk factors or symptoms of suspected CAD underwent coronary computed tomography. CACSs were measured using Agatston method and stratified into 4 groups: 0, 1-99, 100-399, and ≥ 400. Antiplatelet therapy was prescribed following physician discretion. Outcomes of interest were MI and bleeding. A mediation analysis was applied to find association pathways. CACS was considered as an independent variable, whereas antiplatelet therapy was considered as a mediator and MI considered the outcome of interest. Results: A total of 7,849 subjects were enrolled. During an average of 9.9 ± 2.4 years follow-up, MI and bleeding events occurred in 2.24% (n = 176) and 2.82% (n = 221) of subjects, respectively. CACSs 100-399 and CAC ≥ 400 were significantly associated with the development of MI [OR 3.14 (1.72, 5.72), and OR 3.22 (1.66, 6.25), respectively, p < 0.001]. Antiplatelet therapy reduced the risk of MI of these corresponding CAC groups with ORs of 0.60 (0.41, 0.78) and 0.56 (0.34, 0.77), p < 0.001]. A risk of bleeding was associated with antiplatelet therapy (only aspirin), anticoagulant, hypertension, male gender and old age. Conclusion: CACS was associated with the development of future MI. The preventive effect of antiplatelet therapy was clearly demonstrated in subjects with CACSs equal to or above 100, but this benefit was partially offset by an increased risk of bleeding.

Causal association pathways between fetuin-A and kidney function: a mediation analysis.

OBJECTIVE: Body mass index (BMI), uric acid, diabetes mellitus, and hypertension are risk factors for reduced kidney function and are associated with fetuin-A levels, but their causal pathways remain unclear. The objective of this study was to investigate this knowledge gap. METHODS: A repeated cross-sectional design was used to assess causal pathway effects of fetuin-A on the estimated glomerular filtration rate (eGFR), which is mediated through BMI, uric acid, diabetes mellitus, and hypertension. RESULTS: Among 2305 participants, the mean eGFR at baseline decreased from 98.7 ± 23.6 mL/minute/1.73 m2 in 2009 to 92.4 ± 22.9 mL/minute/1.73 m2 in 2014. Fetuin-A was significantly associated with eGFR , suggesting that increasing fetuin-A levels predict a decrease in eGFR. Additionally, the indirect effect of fetuin-A on eGFR, as assessed through BMI, was also significant. The effects of fetuin-A on eGFR through other mediation pathways showed variable results. CONCLUSIONS: Our study revealed a possible role of fetuin-A in the etiology of declining renal function through mediating body mass index, uric acid, diabetes mellitus, and hypertension via complex causal pathways. Further studies to clarify these mediated effects are recommended.

Treatment of slow-channel congenital myasthenic syndrome in a Thai family with fluoxetine.

The slow-channel congenital myasthenic syndrome is an autosomal dominant neuromuscular disorder caused by mutations in different subunits of the acetylcholine receptor. Fluoxetine, a common antidepressant and long-lived open-channel blocker of acetylcholine receptor, has been reported to be beneficial in the slow-channel congenital myasthenic syndrome. Here we report a prospective open label study of fluoxetine treatment in some affected members of a Thai family with slow-channel congenital myasthenic syndrome caused by a novel p.Gly153Ala (c.518G > C) mutation in CHRNA1 in the AChR α subunit. These patients showed significant clinical improvement following fluoxetine treatment but their respiratory function responded variably.

Comparison of the immunogenicity of ChAdOx1 nCoV-19 vaccine against the wild-type and delta variants in kidney transplant recipients and healthy volunteers.

Little is known about immunogenicity after ChAdOx1 nCov-19 vaccination after transplantation. We assessed the vaccine response by antibody testing, surrogate neutralization test (sVNT) against wild-type (WT) and delta variant (DT), and T cell assay in 83 kidney transplant recipients (KTRs) and 52 healthy volunteers (HVs). For KTRs, a positive anti-RBD antibody was seen in 2.8% after one dose and 15.7% after two doses of the vaccine. After two doses, the positivity rate by sVNT was equal (4.9% each, for WT and DT) and was 13.4% by T cell response. Post two doses, KTRs had significantly lower geometric mean titer than HVs (1.93 [95% CI: 1.39-2.69] vs. 248.3 [95% CI: 203.7-302.6] BAU/ml, respectively, p < .001). Daily mycophenolate dose of ≥1000 mg significantly associated with negative seroconversion [risk ratio (RR) of 0.33, 95% CI: 0.15-0.72, p = .005]. Compared with cyclosporine, daily tacrolimus dose of ≤3 mg and >3 mg of tacrolimus significantly associated with negative seroconversion [RR = 0.38 (95% CI, 0.17-0.85, p = .018) and RR = 0.16 (95% CI, 0.37-0.73, p = .018)], respectively. The vaccine was safe and well-tolerated but the immune response after the two doses of ChAdOx1 nCov-19 vaccine in KTRs was very low.