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.

ObjectiveTo investigate the diagnosis and treatment of familial hypokalemic periodic paralysis with acidosis. MethodsThe proband's medical history， clinical manifestations， laboratory examinations and imaging characteristics were retrospectively analyzed， and prevalence situation of family members was investigated in detail. Next generation sequencing technology was used to detect the pathogenic gene loci related to periodic paralysis， and the relevant literatures were summarized. ResultsThe proband was definitely diagnosed as familial hypokalemic periodic paralysis. There was a heterozygous mutation in the SCN4A gene of the proband， which was c.2006G>A， resulting in amino acid changes R669H.The proband's grandfather， father and uncle shared the same variation. ConclusionsFamilial hypokalemic periodic paralysis with paroxysmal acidosis is rare， which is easily misdiagnosed as renal tubular acidosis. c 2006G>A mutation in SCN4A gene is the molecular basis of the disease in this family. The clinical phenotypes of different gene mutations are different， and gene screening is helpful for diagnosis and treatment.

To efficiently remove all recurrent lymph nodes (rLNs) and minimize complications, we developed a combination approach that consisted of ⁶⁸Gallium prostate-specific membrane antigen (PSMA) ligand positron emission tomography (PET)/computed tomography (CT) and integrated indocyanine green (ICG)-guided salvage lymph node dissection (sLND) for rLNs after radical prostatectomy (RP). Nineteen patients were enrolled to receive such treatment. ⁶⁸Ga-PSMA ligand PET/CT was used to identify rLNs, and 5 mg of ICG was injected into the space between the rectum and bladder before surgery. Fluorescent laparoscopy was used to perform sLND. While extensive LN dissection was performed at level I, another 5 mg of ICG was injected via the intravenous route to intensify the fluorescent signal, and laparoscopy was introduced to intensively target stained LNs along levels I and II, specifically around suspicious LNs, with ⁶⁸Ga-PSMA ligand PET/CT. Next, both lateral peritonea were exposed longitudinally to facilitate the removal of fluorescently stained LNs at levels III and IV. In total, pathological analysis confirmed that 42 nodes were rLNs. Among 145 positive LNs stained with ICG, 24 suspicious LNs identified with ⁶⁸Ga-PSMA ligand PET/CT were included. The sensitivity and specificity of ⁶⁸Ga-PSMA ligand PET/CT for detecting rLNs were 42.9% and 96.6%, respectively. For ICG, the sensitivity was 92.8% and the specificity was 39.1%. At a median follow-up of 15 (interquartile range [IQR]: 6-31) months, 15 patients experienced complete biochemical remission (BR, prostate-specific antigen [PSA] <0.2 ng ml^-1), and 4 patients had a decline in the PSA level, but it remained >0.2 ng ml^-1. Therefore, ⁶⁸Ga-PSMA ligand PET/CT integrating ICG-guided sLND provides efficient sLND with few complications for patients with rLNs after RP.
Gallium Isotopes ; Gallium Radioisotopes ; Humans ; Indocyanine Green ; Ligands ; Lymph Node Excision ; Lymphatic Metastasis/diagnostic imaging* ; Male ; Neoplasm Recurrence, Local/surgery* ; Positron Emission Tomography Computed Tomography ; Prostate ; Prostatectomy ; Prostatic Neoplasms/surgery* ; Salvage Therapy

Background Essential and non-essential elements have an important impact on the development of the central nervous system during fetal development. Due to their less developed brain, preterm infants are more sensitive to element exposure, and are high-risk groups of neurodevelopmental abnormalities. However, it is not clear whether the effects of element exposure in utero on postpartum neurodevelopment are different between full-term infants and preterm infants. Objective To evaluate the effects of element exposure levels during pregnancy on neurodevelopment of children aged 6-24 months (of corrected age), and compare the effects between preterm and full-term children. Methods A prospective study design was adopted and this study was conducted based on the Maoming Birth Cohort Study (MBCS) in Maoming City, Guangdong Province. Twenty elements in cord blood of 197 preterm infants and 297 full-term infants were measured, including 11 essential trace elements [vanadium (V), chromium (Cr), manganese (Mn), cobalt (Co), nickel (Ni), copper (Cu), zinc (Zn), selenium (Se), strontium (Sr), tin (Sn), and iron (Fe)], and 9 non-essential trace elements [aluminum (Al), arsenic (As), thallium (Tl), lead (Pb), uranium (U), cerium (Ce), antimony (Sb), cadmium (Cd), and yttrium (Y)]. The neurodevelopment of the children at 6, 12, and 24 months were evaluated by the Ages and Stages Questionnaires-the Third Edition (ASQ-3). A generalized estimating equation (GEE) model was adopted to evaluate the associations between elements and neurodevelopment in full-term and preterm children separately. Results The positive rates of 10 elements (Mn, Cu, Zn, Se, Sr, Fe, Sb, Tl, Pb, and As) in cord blood were greater than 80%. Among the preterm birth children, the results of GEE analysis showed that after adjusting for the covariates, for each increase of interquartile range (IQR) in ln-transformed concentration, As was associated with problems/delay in the communication and problem-solving sub-scales, with the adjusted odds ratios (OR) and 95% confidence intervals (CI) of 1.36 (1.03-1.80) and 1.55 (1.10-2.20), respectively; the adjusted OR (95%CI) of problems/delay in the fine motor and problem-solving sub-scales were 1.44 (1.00-2.07) and 1.76 (1.09-2.84) for Sb, respectively; the adjusted OR (95%CI) of problems/delay in the communication sub-scale was 1.37 (1.09-1.74) for Se. No statistically significant associations between umbilical cord blood element concentrations and neurodevelopment indicators were observed among full-term children. The results of stratified analysis by sex showed that the associations between umbilical cord blood element concentrations and neurodevelopment problems/delay were only significant among female preterm children. Conclusion Exposures to As, Se, and Sb during pregnancy may increase the risk of neurodevelopment problems/delay in preterm children aged 6-24 months, and female seem to be more vulnerable.

ObjectiveTo assess the diagnostic efficiency of different diffusion models （DTI， DKI and NODDI） in grading glioma and predicting IDH-1 mutation status， and to further build logistic regression prediction models. MethodsTotally 66 patients （22 females； mean age： 47.8） with pathologically proved gliomas were retrospectively included. All cases underwent bipolar spin echo diffusion examination. Parameters of DKI （MK； Ka； Kr）， DTI （MD and FA） and NODDI （intracellular volume fraction： icvf， orientation dispersion index： odi） were derived. ROIs were manually drawn and corresponding average values were calculated. Logistic regression was performed to build a predictive model. ROC curve was obtained， and Hosmer-lemeshow test was carried out to test the goodness of fit. ResultsDKI， DTI and NODDI parameters were significantly different between HGGs and LGGs （P < 0.01）. And among all diffusion parameters， a further logistic regression model for grading glioma only included age and MK， which showed the highest diagnostic value ［AUC=0.88， AUC 95%CI （0.79， 0.96）］. Hosmer-lemeshow Test present excellent of goodness of fit. With IDH-1 mutation status， NODDI showed no significant value for distinction， whereas DKI and DTI can significantly differentiate IDH-1 mutated and non-mutated glioma （P < 0.05）. Further logistic regression only selected Kr （P <0.01） in the model， which demonstrated the highest diagnostic value ［AUC=0.72， AUC 95%CI （0.59， 0.85）］. ConclusionsDKI is superior to DTI and NODDI in grading gliomas and identifying IDH-1 mutation status. The model of MK value and age variables present the best discriminatory capacity for grading glioma and Kr value may serve as a potential predictive index for identify IDH-1 mutation.

【Background】 The aim of this prospective randomized study was to evaluate the feasibility of subtotal thyroidectomy leaving a unilateral remnant based on the upper pole. 【Methods】 Patients who underwent the subtotal thyroidectomy and isthmusectomy leaving either a unilateral remnant based on the upper pole（GroupⅠ ，59 patients）or with the bilateral dorsal thyroid tissue remained（Group Ⅱ，54 patients）were prospectively compared in operation time， blood loss，recurrence，and postoperative complications.【Results】The operation time remained similar between the two groups，but the blood loss，the reoperation time，recurrent laryngeal nerve injury，and recurrence in GroupⅠwere much less than those in Group Ⅱ. In addition ，no postoperative hemorrhage occurred in GroupⅠ. Three patients （5.56%） underwent postoperative hemorrhage in Group Ⅱ. Two patients（3.39%）in GroupⅠand 4 patients（7.40%）in Group Ⅱ experienced transient hypocalcemia.【Conclusion】In terms of blood loss，reoperation time，postoperative complication， and recurrence ，subtotal thyroidectomy with recurrent laryngeal nerves identification and the unilateral superior pole remnant of the gland provides a better outcome than subtotal thyroidectomy with bilateral dorsal thyroid tissue remnant.

【Objective】Serum gamma-glutamyltransferase（GGT）has recently been implicated in the pathogenesis of atherosclerosis and coronary heart disease（CHD）. We aimed to evaluate the association between the serum GGT level and the 10-year risk score for CHD（Framingham Risk Score，FRS）in a Chinese population.【Methods】We conducted a population-based cross-sectional study in 9，544 Guangzhou residents aged 40 years and older. Participants were divided into four quartiles according to their GGT levels：Quartile 1 <15 U/L（n=2 407），Quartile 2 15~19.9 U/L（n=2 302）， Quartile 3 20~28.9 U/L（n=2 442），and Quartile 4 ≥29 U/L（n=2 393）. The multivariate logistic regression analysis was used to assess the incidence of intermediate and high risk of developing CHD at 10 years（FRS≥10%）in relation to each quartile increase of serum GGT level.【Results】The incidence of FRS≥10% increased with elevating serum GGT levels（P for trend<0.001）. Compared with the lowest quartile of serum GGT level ，the adjusted odds ratio in the highest quartile was 1.72（95% confidence interval 1.28 to 2.29）.【Conclusion】Serum GGT level is associated with the FRS for CHD ，and might be used as an adjuvant marker for identifying patients at increased risk of cardiovascular events and early intervention.

The present study analyzed the predictive value of combined analysis of collapsin response mediator protein 4 (CRMP4) methylation levels and the Cancer of the Prostate Risk Assessment (CAPRA-S) Postsurgical score of patients who required adjuvant hormone therapy (AHT) after radical prostatectomy (RP). We retrospectively analyzed 305 patients with prostate cancer (PCa) who received RP and subsequent androgen deprivation therapy (ADT). Two hundred and thirty patients with clinically high-risk PCa underwent immediate ADT, and 75 patients with intermediate risk PCa underwent deferred ADT. CRMP4 methylation levels in biopsies were determined, and CAPRA-S scores were calculated. In the deferred ADT group, the values of the hazard ratios for tumor progression and cancer-specific mortality (CSM) in patients with ≥15% CRMP4 methylation were 6.81 (95% CI: 2.34-19.80) and 12.83 (95% CI: 2.16-26.10), respectively. Receiver-operating characteristic curve analysis indicated that CRMP4 methylation levels ≥15% served as a significant prognostic marker of tumor progression and CSM. In the immediate ADT group, CAPRA-S scores ≥6 and CRMP4 methylation levels ≥15% were independent predictors of these outcomes (uni- and multi-variable Cox regression analyses). The differences in the 5-year progression-free survival between each combination were statistically significant. Combining CAPRA-S score and CRMP4 methylation levels improved the area under the curve compared with the CRMP4 or CAPRA-S model. Therefore, CRMP4 methylation levels ≥15% were significantly associated with a poor prognosis and their combination with CAPRA-S score accurately predicted tumor progression and metastasis for patients requiring AHT after RP.
Aged ; Androgen Antagonists/therapeutic use* ; Biomarkers, Tumor/blood* ; Female ; Hormone Replacement Therapy ; Humans ; Male ; Methylation ; Middle Aged ; Muscle Proteins/metabolism* ; Neoplasm Grading ; Neoplasm Metastasis ; Neoplasm Staging ; Prognosis ; Progression-Free Survival ; Prostatectomy ; Prostatic Neoplasms/metabolism* ; Retrospective Studies ; Risk Assessment ; Treatment Outcome

OBJECTIVETo establish a NOD/SCID mouse model with human immune reconstitution and observe its immune response to human triple-negative breast cancer xenograft.

METHODSTwenty-four NOD/SCID mice without immune leakage were subjected to cyclophosphamide (CTX) treatment 3 days prior to immune reconstitution with human peripheral blood mononuclear cell (PBMC) injection and subcutaneous transplantation of human triple-negative breast cancer MDA-MB-231 cells, CTX treatment and PBMC injection without tumor cell transplantation, MDA-MB-231 cell transplantation only, or no treatments. The tumor growth and immune responses of the mice were observed at regular intervals.

RESULTSCompared with the tumor-bearing mice, the tumor-bearing mice with immune reconstitution showed prolonged incubation period of tumor formation, slower tumor growth rate and increased survival rate. Human IgG and CD3(+) T cells were detected in the peripheral blood of the mice 1 week after human PBMC injection. The percentage of CD3(+) T cells in the spleen cells was 55.3% at 9 weeks in tumor-bearing mice with immune reconstitution and 52.7% in tumor-bearing mice without immune reconstitution. The spleen index of the tumor-bearing mice with immune reconstitution was much higher than that in mice with only immune reconstitution and the control mice (9.64 vs 3.82∓0.31 and 1.51∓0.14 mg/g).

CONCLUSIONA stable NOD/SCID mouse model with immune reconstitution has been established successfully, which shows immune responses to triple-negative breast cancer xenografts and allows studies of immunological therapy study of triple-negative breast cancer.

Animals ; Disease Models, Animal ; Humans ; Leukocytes, Mononuclear ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Neoplasm Transplantation ; Spleen ; immunology ; Triple Negative Breast Neoplasms ; immunology

OBJECTIVETo estimate the diagnostic accuracy of magnetic resonance(MR) in restaging of rectal cancer after preoperative chemoradiotherapy(CRT).

METHODSComprehensive search of literature concerning the diagnosis of MR for rectal cancer after preoperative CRT was performed from databases of PubMed, EMbase, OVID and WOK. Sensitivity and specificity of MR on restaging of rectal cancer after preoperative CRT were investigated by SAS and MetaDiSc software.

RESULTSThirteen articles including 749 patients were enrolled in this meta-analysis. For T3-T4 stage, sensitivity of MR was 82.1%(95%CI:67.9%-90.9%), specificity was 53.5%(95%CI:39.3%-67.3%), and diagnostic odds ratio(DOR) was 5.34(2.73, 6.59). For lymph node involvement, sensitivity of MR was 61.8%(95%CI:50.7%-71.8%), specificity was 72.0%(95%CI:61.3%-80.7%), and DOR was 4.33(95%CI:2.84-6.59). For circumferential resection margin(CRM) by MR, pooled sensitivity was 85.4%(95%CI:60.5%-95.7%), specificity was 80.0%(95%CI:57.4%-92.3%), and DOR was 27.62(95%CI:13.03-58.55).

CONCLUSIONSRestaging accuracy of T3-T4 and lymph nodes involvement of rectal cancer after preoperative CRT by MR is not high. MR may be a good method to make reassessment of CRM. To avoid overtreatment for T0-T2, negative lymph node and circumferential resection of rectal cancer, restaging by MR after preoperative CRT is important.

Chemoradiotherapy ; Humans ; Magnetic Resonance Imaging ; Magnetic Resonance Spectroscopy ; Neoplasm Staging ; Rectal Neoplasms ; pathology ; therapy