BACKGROUNDThere is a relatively high failure rate of the femoral component in patients with avascular necrosis at the intermediate-term follow-up. Improving the geometrical fit of the femoral stem against the medullary canal may help to provide long-term survivorship of the hip replacement for patients with avascular necrosis.

METHODSWe designed a specific stem, based on morphometric studies of proximal femoral canals in Chinese avascular necrosis patients and evaluated the stem by finite element analyses, comparing the novel stem with two commercially available and commonly used stems.

RESULTSThe morphometric data from avascular necrosis patients showed specific geometric differences in the proximal femoral canal, including profile curves in both the sagittal and coronary planes than the patients with femoral neck fracture. The shorter stemmed prostheses (Fitmore(®) and our stem) performed better than the longer stemmed prosthesis (VerSys(®)).

CONCLUSIONSThis is the first study to investigate the femoral geometries of Chinese avascular necrosis patients. Our stem provides better stability and is theoretically beneficial to bone ingrowth, which may increase the long-term stability and fixation of the implant.

Adult ; Aged ; Biomechanical Phenomena ; Female ; Femur Head Necrosis ; physiopathology ; Finite Element Analysis ; Humans ; Male ; Middle Aged

OBJECTIVE: We hypothesized that DNA methylation of development-related genes may occur in endometrial cancer (EC)/ovarian cancer (OC) and may be detected in cervical scrapings. METHODS: We tested methylation status by quantitative methylation-specific polymerase chain reaction for 14 genes in DNA pools of endometrial and OC tissues. Tissues of EC/normal endometrium, OC/normal ovary, were verified in training set using cervical scrapings of 10 EC/10 OC patients and 10 controls, and further validated in the testing set using independent cervical scrapings in 30 EC/30 OC patients and 30 controls. We generated cutoff values of methylation index (M-index) from cervical scrapings to distinguish between cancer patients and control. Sensitivity/specificity of DNA methylation biomarkers in detecting EC and OC was calculated. RESULTS: Of 14 genes, 4 (PTGDR, HS3ST2, POU4F3, MAGI2) showed hypermethylation in EC and OC tissues, and were verified in training set. POU4F3 and MAGI2 exhibited hypermethylation in training set were validated in independent cases. The mean M-index of POU4F3 is 78.28 in EC and 20.36 in OC, which are higher than that in controls (6.59; p<0.001 and p=0.100, respectively), and that of MAGI2 is 246.0 in EC and 12.2 in OC, which is significantly higher that than in controls (2.85; p<0.001 and p=0.480, respectively). Sensitivity and specificity of POU4F3/MAGI2 were 83%–90% and 69%–75% for detection of EC, and 61% and 62%–69% for the detection of OC. CONCLUSION: The findings demonstrate the potential of EC/OC detection through testing for DNA methylation in cervical scrapings.
Biomarkers ; DNA Methylation ; DNA ; Endometrial Neoplasms ; Endometrium ; Female ; Humans ; Methylation ; Ovarian Neoplasms ; Ovary ; Polymerase Chain Reaction ; Sensitivity and Specificity

OBJECTIVE: Hypermethylation of human papillomavirus (HPV) and host genes has been reported in cervical cancer. However, the degree of methylation of different HPV types relative to the severity of the cervical lesions remains controversial. Studies of the degree of methylation associated with the host gene and the HPV genome to the severity of cervical lesions are rare. We examined the association of methylation status between host genes and late gene 1 (L1) regions of HPV16, 18, 52, and 58 in cervical brushings. METHODS: Cervical brushings from 147 HPV-infected patients were obtained. The samples comprised normal (n=28), cervical intraepithelial neoplasia (CIN) 1 (n=45), CIN2 (n=13), and CIN3/carcinoma in situ (n=61). The methylation status of HPV and host genes was measured using bisulfite pyrosequencing and quantitative methylation-specific polymerase chain reaction (PCR). RESULTS: The degree of methylation of L1 in HPV16, 18, and 52 was associated with the severity of the cervical lesion. In HPV52, C-phosphate-G (CpG) sites 6368m, 6405m, and 6443m showed significantly higher methylation in lesions ≥CIN3 (p=0.005, 0.003, and 0.026, respectively). Methylation of most HPV types except HPV52 (r<−0.1) was positively correlated with the degree of methylation of host genes including PAX1 and SOX1 (0.4≤r≤0.7). Combining HPV methylation with PAX1 methylation improved the clustering for ≥CIN2. CONCLUSION: Our study showed that the degree of L1 methylation of HPV16, 18, and 52 but not 58 is associated with the severity of cervical lesions. The association between HPV methylation and host gene methylation suggests different responses of host cellular epigenetic machinery to different HPV genotypes.
Cervical Intraepithelial Neoplasia* ; DNA Methylation ; Epigenomics ; Genome ; Genotype ; Human papillomavirus 16 ; Humans ; Methylation* ; Papillomaviridae ; Polymerase Chain Reaction ; Uterine Cervical Neoplasms

OBJECTIVEAccuracy of diagnostic methods for detecting Helicobacter pylori (H. pylori) infection among patients with bleeding peptic ulcers has not been thoroughly investigated. The aim of this study was to compare the diagnostic tests and their combined usage in detection of H. pylori infection in patients with bleeding gastric ulcers and without the use of nonsteroidal anti-inflammatory drugs.

METHODSA total of 57 patients who presented with bleeding gastric ulcers by endoscopy were enrolled. The status of H. pylori was identified by performing the rapid urease test (RUT), histology and (13)C-labeled urea breath test (UBT). The criteria for having H. pylori infection was a minimum of two positive tests.

RESULTSThe prevalence of H. pylori infection in our patient group was 80.7%. Among the three tests used: RUT, histology, and UBT, sensitivities were 56.5%, 97.8% and 100%, while specificities were 100%, 45.5% and 81.8%, respectively. The overall accuracies of the tests were 78.3%, 71.6% and 90.9%, respectively. Although UBT obtained significantly higher accuracy than histology (P = 0.02) as opposed to RUT (P = 0.11), UBT had significantly higher sensitivity than RUT (P < 0.001). In terms of combining any two of the three tests, more accuracy (98.9%) was achieved when both UBT and histology were used to confirm the diagnosis of the other. Conversely, failure to use combined tests generated the potential of missing a proper H. pylori diagnosis.

CONCLUSIONSUBT is superior to the other two tests in bleeding gastric ulcers. RUT lacks sensitivity for detection of H. pylori infection. However, the concomitant use of UBT and histology seems to be more accurate when gastric ulcers present with bleeding.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Breath Tests ; Female ; Helicobacter Infections ; diagnosis ; pathology ; Helicobacter pylori ; Humans ; Male ; Middle Aged ; Peptic Ulcer Hemorrhage ; complications ; Sensitivity and Specificity ; Stomach Ulcer ; complications ; Urea

Objectives: An Asian Gynecologic Oncology Group phase III randomized trial was conducted to determine whether maintenance chemotherapy could improve progression-free survival (PFS) in stages III/IV ovarian cancer. Methods: Between 2007 and 2014, 45 newly-diagnosed ovarian cancer patients were enrolled after complete remission and randomized (1:1) to arm A (4-weekly carboplatin area under the curve 4 and pegylated liposomal doxorubicin [PLD] 30 mg/m2, n=24) for 6 cycles or arm B (observation, n=21). The primary end-point was PFS. A post hoc translational study was conducted to deep sequence BRCA/homologous recombination deficiency (HRD) genes, because BRCA/HRD mutations (BRCA/HRDm) are known to be associated with better prognosis. Results: Enrollment was slow, accrual was closed when 7+ years had passed. With a medianfollow-up of 88.9 months, the median PFS was significantly better in arm A (55.5 months) than arm B (9.2 months) (hazard ratio [HR]=0.40; 95% confidence interval [CI]=0.19–0.87; p=0.020), yet the median overall survival was not significantly different in arm A (not reached) than arm B (95.1 months) (p=0.148). Overall grade 3/4 adverse events were more frequent in arm A than arm B (60.9% vs 0.0%) (p<0.001). Quality of life was generally not significantly different. Distribution of BRCA1/2m or BRCA/HRDm was not significantly biased between the two arms. Wild-type BRCAon-HRD subgroup seemed to fare better with maintenance therapy (HR=0.35; 95% CI=0.11–1.18; p=0.091). Conclusions Despite limitations in small sample size, it suggests that maintenance carboplatin-PLD chemotherapy could improve PFS in advanced ovarian cancer.

Objective: The characteristics of patients with metachronous breast and ovarian malignancies and the pathogenic role of BRCA1/2 mutations remain poorly understood. We investigated these issues through a review of hospital records and nationwide Taiwanese registry data, followed by BRCA1/2 mutation analysis in hospital-based cases. Methods: We retrospectively retrieved consecutive clinical records of Taiwanese patients who presented with these malignancies to our hospital between 2001 and 2017. We also collected information from the Data Science Center of the Taiwan Cancer Registry (TCR) between 2007 and 2015. Next-generation sequencing and multiplex ligation-dependent probe amplification were used to identify BRCA1/2 mutations and large genomic rearrangements, respectively. When BRCA1/2 mutations were identified in index cases, pedigrees were reconstructed and genetic testing was offered to family members. Results: A total of 12,769 patients with breast cancer and 1,537 with ovarian cancer were retrieved from our hospital records. Of them, 28 had metachronous breast and ovarian malignancies. We also identified 113 cases from the TCR dataset. Eighteen hospital-based cases underwent BRCA1/2 sequencing and germline pathogenic mutations were detected in 7 patients (38.9%, 5 in BRCA1 and 2 in BRCA2). All BRCA1/2 mutation carriers had ovarian high-grade serous carcinomas. Of the 12 patients who were alive at the time of analysis, 5 were BRCA1/2 mutation carriers. All of them had family members with BRCA1/2-associated malignancies. Conclusions Our results provide pilot evidence that BRCA1/2 mutations are common in Taiwanese patients with metachronous breast and ovarian malignancies, supporting the clinical utility of genetic counseling.

Arm ; Asian Continental Ancestry Group ; Bias (Epidemiology) ; Carboplatin ; Disease-Free Survival ; Doxorubicin ; Drug Therapy ; Follow-Up Studies ; Humans ; Maintenance Chemotherapy ; Ovarian Neoplasms ; Prognosis ; Quality of Life ; Recombination, Genetic ; Sample Size

Background/Aims: Chronic hepatitis C (CHC) patients who failed antiviral therapy are at increased risk for hepatocellular carcinoma (HCC). This study assessed the potential role of metformin and statins, medications for diabetes mellitus (DM) and hyperlipidemia (HLP), in reducing HCC risk among these patients. Methods: We included CHC patients from the T-COACH study who failed antiviral therapy. We tracked the onset of HCC 1.5 years post-therapy by linking to Taiwan’s cancer registry data from 2003 to 2019. We accounted for death and liver transplantation as competing risks and employed Gray’s cumulative incidence and Cox subdistribution hazards models to analyze HCC development. Results: Out of 2,779 patients, 480 (17.3%) developed HCC post-therapy. DM patients not using metformin had a 51% increased risk of HCC compared to non-DM patients, while HLP patients on statins had a 50% reduced risk compared to those without HLP. The 5-year HCC incidence was significantly higher for metformin non-users (16.5%) versus non-DM patients (11.3%; adjusted sub-distribution hazard ratio [aSHR]=1.51; P=0.007) and metformin users (3.1%; aSHR=1.59; P=0.022). Statin use in HLP patients correlated with a lower HCC risk (3.8%) compared to non-HLP patients (12.5%; aSHR=0.50; P<0.001). Notably, the increased HCC risk associated with non-use of metformin was primarily seen in non-cirrhotic patients, whereas statins decreased HCC risk in both cirrhotic and non-cirrhotic patients. Conclusions Metformin and statins may have a chemopreventive effect against HCC in CHC patients who failed antiviral therapy. These results support the need for personalized preventive strategies in managing HCC risk.

OBJECTIVETo observe the effect of combining red yeast rice and Lactobacillus casei (L. casei) in lowering cholesterol in patients with primary hyperlipidemia, the later has also been shown to remove cholesterol in in vitro studies.

METHODSA double-blind clinical trial was conducted to evaluate the cholesterol-lowering effect of the combination of red yeast rice and L. casei. Sixty patients with primary hyperlipidemia were recruited and randomized equally to either the treatment group (red yeast rice + L. casei) or the control group (red yeast rice + placebo). One red yeast rice capsule and two L. casei capsules were taken twice a day. The treatment lasted for 8 weeks, with an extended follow-up period of 4 weeks. The primary endpoint was a difference of serum low-density lipoprotein cholesterol (LDL-C) level at week 8.

RESULTSAt week 8, the LDL-C serum level in both groups was lower than that at baseline, with a decrease of 33.85±26.66 mg/dL in the treatment group and 38.11±30.90 mg/dL in the control group; however, there was no statistical difference between the two groups (P>0.05). The total cholesterol was also lower than the baseline in both groups, yet without a statistical difference between the two groups. The only statistically signifificant difference between the two groups was the average diastolic pressure at week 12, which dropped by 2.67 mm Hg in the treatment group and increased by 4.43 mm Hg in the placebo group (P<0.05). The antihypertensive activity may be associated with L. casei. Red yeast rice can signifificantly reduce LDL-C, total cholesterol and triglyceride.

CONCLUSIONThe combination of red yeast rice and L. casei did not have an additional effect on lipid profifiles.