Purpose: Total neoadjuvant therapy (TNT) is becoming the standard of care for locally advanced rectal cancer. However, surgery is deferred for months after completion, which may lead to fibrosis and increased surgical difficulty. The aim of this study was to assess whether TNT (TNT-RAPIDO) is associated with increased difficulty of total mesorectal excision (TME) compared with long-course chemoradiotherapy (LCRT) and upfront surgery. Methods: Twelve laparoscopic videos of low anterior resection with TME for rectal cancer were prospectively collected from January 2020 to October 2021, with 4 videos in each arm. Seven colorectal surgeons assessed the videos independently, graded the difficulty of TME using a visual analog scale and attempted to identify which category the videos belonged to. Results: The median age was 67 years, and 10 patients were male. The median interval to surgery from radiotherapy was 13 weeks in the LCRT group and 24 weeks in the TNT-RAPIDO group. There was no significant difference in the visual analog scale for difficulty in TME between the 3 groups (LCRT, 3.2; TNT-RAPIDO, 4.6; upfront, 4.1; P=0.12). A subgroup analysis showed similar difficulty between groups (LCRT 3.2 vs. TNT-RAPIDO 4.6, P=0.05; TNT-RAPIDO 4.6 vs. upfront 4.1, P=0.54). During video assessments, surgeons correctly identified the prior treatment modality in 42% of the cases. TNT-RAPIDO videos had the highest recognition rate (71%), significantly outperforming both LCRT (29%) and upfront surgery (25%, P=0.01). Conclusion TNT does not appear to increase the surgical difficulty of TME.

Background/Aims: Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1–3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy. Methods: We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment. Results: The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset. Conclusions Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.

Cardiac-resident macrophages (CRMs) play important roles in homeostasis, cardiac function, and remodeling. Although CRMs play critical roles in cardiac regeneration of neonatal mice, their roles are yet to be fully elucidated. Therefore, this study aimed to investigate the dynamic changes of CRMs during cardiac ontogeny and analyze the phenotypic and functional properties of CRMs in the promotion of cardiac regeneration. During mouse cardiac ontogeny, four CRM subsets exist successively: CX₃CR1⁺CCR2^-Ly6C^-MHCII^- (MP1), CX₃CR1^lowCCR2^lowLy6C^-MHCII^- (MP2), CX₃CR1^-CCR2⁺Ly6C⁺MHCII^- (MP3), and CX₃CR1⁺CCR2^-Ly6C^-MHCII⁺ (MP4). MP1 cluster has different derivations (yolk sac, fetal liver, and bone marrow) and multiple functions population. Embryonic and neonatal-derived-MP1 directly promoted cardiomyocyte proliferation through Jagged-1-Notch1 axis and significantly ameliorated cardiac injury following myocardial infarction. MP2/3 subsets could survive throughout adulthood. MP4, the main population in adult mouse hearts, contributed to inflammation. During ontogeny, MP1 can convert into MP4 triggered by changes in the cellular redox state. These findings delineate the evolutionary dynamics of CRMs under physiological conditions and found direct evidence that embryonic and neonatal-derived CRMs regulate cardiomyocyte proliferation. Our findings also shed light on cardiac repair following injury.

INTRODUCTION: In Singapore, non-anaesthesiologists generally administer sedation during gastrointestinal endoscopy. The drugs used for sedation in hospital endoscopy centres now include propofol in addition to benzodiazepines and opiates. The requirements for peri-procedural monitoring and discharge protocols have also evolved. There is a need to develop an evidence-based clinical guideline on the safe and effective use of sedation by non-anaesthesiologists during gastrointestinal endoscopy in the hospital setting. METHODS: The Academy of Medicine, Singapore appointed an expert workgroup comprising 18 gastroenterologists, general surgeons and anaesthesiologists to develop guidelines on the use of sedation during gastrointestinal endoscopy. The workgroup formulated clinical questions related to different aspects of endoscopic sedation, conducted a relevant literature search, adopted Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology and developed recommendations by consensus using a modified Delphi process. RESULTS: The workgroup made 16 recommendations encompassing 7 areas: (1) purpose of sedation, benefits and disadvantages of sedation during gastrointestinal endoscopy; (2) pre-procedural assessment, preparation and consent taking for sedation; (3) Efficacy and safety of drugs used in sedation; (4) the role of anaesthesiologist administered sedation during gastrointestinal endoscopy; (5) performance of sedation; (6) post-sedation care and discharge after sedation; and (7) training in sedation for gastrointestinal endoscopy for non-anaesthesiologists. CONCLUSION These recommendations serve to guide clinical practice during sedation for gastrointestinal endoscopy by non-anaesthesiologists in the hospital setting.
Conscious Sedation ; Endoscopy, Gastrointestinal ; Hospitals ; Humans ; Hypnotics and Sedatives ; Singapore

Antibodies, Bacterial ; COVID-19/prevention & control* ; Humans ; Injection Site Reaction ; RNA, Messenger ; Vaccination/adverse effects*

INTRODUCTION: Drug allergies are often self-reported but of unknown accuracy. We carried out a prospective study to examine the utility and safety of formal allergology evaluation, and to identify factors associated with accurate drug allergy labels. METHOD: All patients who underwent drug allergy evaluation in our clinic during the study period were recruited. Baseline demographics, characteristics of index hypersensitivity reaction and outcomes of evaluation were recorded. RESULTS: A total of 331 patients from March 2019 to June 2021 completed drug allergy evaluation to index drugs of concern. There were 123 (37%) male patients, and the mean age was 49 years (standard deviation 17). There were 170 beta-lactam antibiotics, 53 peri-operative drugs, 43 others, 38 non steroidal anti-inflammatory drugs, and 27 non-beta-lactam antibiotic evaluations. Index reaction occurred within 5 years in 165 (50%) patients, with latency of less than 4 hours in 125 (38%) patients. The most common index reactions were rash, angioedema and urticaria. There were 57 (17%) evaluations stratified as low risk, 222 (67%) moderate risk, and 52 (16%) high risk based on multidisciplinary consensus. Allergy label was found to be false (negative drug evaluation) in 248 (75%) patients, while 16/237 (7%) skin tests, 44/331 (13%) in-clinic graded challenge, and 23/134 (17%) home prolonged challenges were positive (true drug allergy). The most common evaluation reactions were rash and urticaria. No cases of anaphylaxis were elicited. CONCLUSION Seventy-five percent of drug allergy labels are inaccurate. Risk-stratified, protocolised allergy evaluation is safe. Prolonged drug challenge increases the sensitivity of drug allergy evaluation and should therefore be performed when indicated.
Humans ; Male ; Middle Aged ; Female ; Prospective Studies ; Drug Hypersensitivity/epidemiology* ; Exanthema ; Urticaria ; Monobactams

Objective:To investigate the effects of Hydroxychloroquine on cell apoptosis in peripheral blood mononuclear cells of systemic lupus erythematosus and its mechanisms.Methods:The peripheral blood mononuclear cells of 30 active SLE patients and 15 healthy persons were separated for cell culture.There were four groups:control group,SLE group and HCQ 5 mg/L and HCQ 25 mg/L group.MTT was used to measure the inhibitory effect.Annexin V/PI flow cytometry was performed to analyze cell apoptosis.Western blot was used to evaluate the expressions of PI3 K,pAKt,mTOR,BCL-2,BAX and caspase-3.Besides,the PBMCs of SLE patients were treated with HCQ 25 mg/L and the PI3K/Akt pathway inhibitor LY294002 20 μmol/L and its cell growth inhibition and apoptosis were observed.Results:Compared with the control group,the cell growth inhibition and apoptosis rate of SLE patients group were significantly increased(P＜0.05);while the cell growth inhibition and apoptosis rate of HCQ 5 mg/L and 25 mg/L were increased significantly than the SLE patients group(P＜0.05).Compared with SLE patients group,the expression levels of PI3K,pAKt,mTOR and BCL-2 of HCQ group were significantly increased while the expression of BAX and caspase-3 decreased significantly (P＜ 0.05).The PI3K/Akt pathway inhibitor LY294002 could block the PBMCs apoptosis of SLE patients.Conclusion:Hydroxychloroquine can promote the PBMCs apoptosis of SLE patients by PI3K/Akt signaling pathways.

· AlM:To analyze the association between the macular thickness and emmetropic, low myopic, moderate myopic and highly myopic eyes.
·METHODS:The 276 teenagers (276 eyes) between 18~28 years treated in our hospital from January, 2013 to May, 2014 were selected, whose corrective visual acuity was≥1.0 and intraocular preasure was ≤21mmHg and who were willing to participate in this research.Forty-nine emmetropic, 72 low myopic, 104 moderate myopic and 51 highly myopic eyes were measured by optical coherence tomography ( OCT ) to detect the central subfield thickness, bitamporal, superior, lateral and inferior region thickness of inner and outer region, average thickness of retinal macula, foveal thickness and retinal volume.The thickness of different parts of macula lutea was measured and statistically compared among emmetropic, low myopic, moderate myopic and highly myopic eyes.
· RESULTS: The central subfield thickness of emmetropic, low myopic, moderate myopic and highly myopic eyes were (225.38±20.97), (230.97±19.15), (227.01±16.92), (231.91 ±18.97 )μm. The average thickness of retinal macula, of emmetropic, low myopic, moderate myopic and highly myopic eyes were (280.92±12.71), (278.15± 11.90), (270.05±12.07), (267.93±11.08) μm.There were no significant differences of center thickness (F=1.253, P=0.291) and central subfield thickness ( F=1.034, P=0.378) between emmetropic, low myopic, moderate myopic and highly myopic eyes.The macular thickness of inner and outer region in moderate myopic eyes was significantly less than that in emmetropic eyes, and there was significant difference (P<0.05).Comparison between low myopic, moderate myopic and highly myopic eyes was carried out and macular thickness of all regions of inner and outer region in moderate myopic group was significantly increased, and there was significant difference (P<0.05).There was no significant difference when compared with the macular thickness of inner and outer region of the highly myopic group (P>0.05).
· CONCLUSlON: ln low myopic eyes of teenagers, the center macular thickness do not become thinner. However, the macular thickness of inner and outer region is thinner than that of emmetropic eyes.Furthermore, with the increase of the degree of the myopia, the amount of macular thinner gradually decreases from outer region to inner region.

OBJECTIVETo study the clinical characteristics of children who suffered from Streptococcus pneumoniae (SP) septicemia and the drug sensitivity of SP strains.

METHODSA retrospective analysis was performed on the clinical data of 25 children with SP septicemia between January 2009 and December 2012.

RESULTSOf the 25 cases, 16 (64%) were aged under 2 years, 5 (20%) were aged 2-5 years, and 4 (16%) were aged over 5 years. Fourteen cases (56%) were complicated by infection of other organs, and 5 cases (20%) had underlying chronic diseases. Fever was the most common clinical manifestation, and the majority presented with remittent fever. Eight patients with pneumonia or pyothorax had pulmonary symptoms. Five patients with purulent meningitis had neurological symptoms, five cases had hepatosplenomegaly and two cases had septic shock. Nineteen cases (76%, 19/25) had significantly elevated white blood cell (WBC) counts, twenty-one cases (84%, 21/25) had significantly elevated serum C-reactive protein (CRP) levels, and eight cases (50%, 8/16) had significantly elevated serum procalcitonin (PCT) levels. The drug sensitivity analysis showed that invasive SP had high resistance rates to penicillin (96%), clindamycin hydrochloride (88%) and erythromycin (84%), and it was completely sensitive to imipenem, vancomycin, levofloxacin and linezolid. The multi-drug resistance rate of invasive SP was up to 88%. Twenty-three cases (92%) were cured or improved after active treatment.

CONCLUSIONSSP septicemia is commonly seen in children aged under 2 years. The most common clinical manifestation is fever, accompanied by elevated WBC count, CRP level and PCT level, and it is usually complicated by pulmonary or brain infection. Resistance to multiple antibiotics is very common in SP strains, so it is important to properly use antibiotics according to drug sensitivity test results. Patients who receive active treatment have a good clinical outcome.

Anti-Bacterial Agents ; therapeutic use ; Bacteremia ; blood ; complications ; drug therapy ; C-Reactive Protein ; analysis ; Calcitonin ; blood ; Calcitonin Gene-Related Peptide ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Microbial Sensitivity Tests ; Pneumococcal Infections ; blood ; complications ; drug therapy ; Protein Precursors ; blood ; Retrospective Studies ; Streptococcus pneumoniae ; drug effects

OBJECTIVETo explore the essential points for diagnosis of pulmonary embolism in children with mycoplasma pneumonia.

METHODRetrospective analysis of the clinical and laboratory data of a pediatric case who developed pulmonary embolism after mycoplasma pneumonia was performed for the key points for diagnosis.

RESULTA-six-year old boy was admitted with chief complaint of fever and cough for half a month, combined with chest pain and mild labored breath. Vital signs were stable. Breathing movement of the left side weakened and there was left lower lobe percussion dullness. Breath sound was found weakened in the left lung, and a few fine crackles were audible. The results of laboratory tests were as follows: mycoplasma antibody (IgM) 1:128, cold agglutinin test 1:1024, blood D dimer 14.81 mg/L; anticardiolipin antibody was positive; plasma protein C activity was 60% (normal range 70% - 130%). Pulmonary artery computed tomographic angiography revealed a mass opaque shadow in left lower lobe, the branch of left lower bronchial artery was partially obstructed. Echocardiography showed tricuspid valve mild regurgitation, estimated pulmonary pressure was 5.1 kPa. Single-photon emission computed tomography indicated that radioactivity distribution was apparently sparse in the dorsal segment, anterior basal segment, outer basal segment and inferior lingular segment of the left lung. The preliminary diagnosis on admission was mycoplasma pneumonia with pleural effusion, pulmonary embolism. Intravenous erythromycin combined with meropenem were administered. Anticoagulation therapy was initiated with low molecular weight heparin and then oral warfarin tablets. Pleural effusion disappeared soon, D dimer descended to 0.38 mg/L, and pulmonary artery pressure declined. After 3-month follow-up, anti-cardiolipin antibody was negative, plasma protein C activity recovered, and lung lesions were absorbed.

CONCLUSIONWhen mycoplasma pneumonia is accompanied by chest pain or dyspnea and there are bloody pleural effusion, pulmonary hypertension, positive antiphospholipid antibody and elevated D dimer, pulmonary embolism should be considered. Diagnosis could be clarified by the result of pulmonary artery computed tomographic angiography.

Antibodies, Antiphospholipid ; blood ; Child ; Fibrin Fibrinogen Degradation Products ; metabolism ; Humans ; Male ; Mycoplasma pneumoniae ; Pneumonia, Mycoplasma ; complications ; diagnosis ; Pulmonary Embolism ; complications ; diagnosis ; Retrospective Studies