Association between hepatic angiosarcoma and end-stage renal disease: nationwide population-based evidence and enriched mutational signature of aristolochic acid exposure.

Hepatic angiosarcoma (HAS) is an aggressive mesenchymal malignancy that remains underexplored with respect to its etiology and mutational landscapes. To clarify the association between HAS and end-stage renal disease (ESRD), we used nationwide data of the National Health Insurance Research Database (NHIRD) in Taiwan, covering ~99% of the population, from 2001 to 2016. To investigate molecular signatures, we performed whole-exome sequencing (WES) in 27 surgical specimens, including nine ESRD-associated cases. The NHIRD analysis demonstrated that HAS ranked second among all angiosarcomas in Taiwan, with the incidence rates of HAS being 0.08, 2.49, and 5.71 per 100,000 person-years in the general population, chronic kidney disease (CKD), and ESRD patients, respectively. The standardized incidence ratios of HAS in CKD and ESRD patients were 29.99 and 68.77, respectively. In comparison with nonhepatic angiosarcoma, the multivariate regression analysis of our institutional cohort confirmed CKD/ESRD as an independent risk factor for HAS (odds ratio: 9.521, 95% confidence interval: 2.995-30.261, p < 0.001). WES identified a high tumor mutation burden (TMB; median: 8.66 variants per megabase) and dominant A:T-to-T:A transversion in HAS with frequent TP53 (81%) and ATRX (41%) mutations, KDR amplifications/gains (56%), and CDKN2A/B deletions (48%). Notably, ESRD-associated HAS had a significantly higher TMB (17.62 variants per megabase, p = 0.01) and enriched mutational signatures of aristolochic acid exposure (COSMIC SBS22, p < 0.001). In summary, a significant proportion of HAS in Taiwan is associated with ESRD and harbors a distinctive mutational signature, which concomitantly links nephrotoxicity and mutagenesis resulting from exposure to aristolochic acid or related compounds. A high TMB may support the eligibility for immunotherapy in treating ESRD-associated HAS. © 2023 The Pathological Society of Great Britain and Ireland.

Temporal Trends of Inflammatory Bowel Diseases in Taiwan from 2016 to 2020: A Population-Based Study.

BACKGROUND: There are scanty population-based studies investigating the incidence and prevalence rates of inflammatory bowel disease (IBD) in Taiwan. AIMS: This study aimed to estimate the nationwide prevalence and incidence of IBD and identify its noticeable trends in Taiwan between 2016 and 2020. METHODS: A retrospective study by analyzing the data from the National Health Insurance Research Database of Taiwan. RESULTS: A total of 2595 patients with catastrophic IBD illness were registered from 2016 to 2020 in Taiwan (CD, 880; UC, 1715). The male-to-female ratio in the study sample was 1.83:1 for CD and 1.69:1 for UC. The median age of those registered with CD and UC was 37 and 47 years, respectively. The incidence rate of CD was 0.65 per 100,000 persons in 2016 and it was increased to 0.81 per 100,000 persons in 2020. The incidence rate of UC was 1.16 per 100,000 persons in 2016 and it was increased to 1.53 in 2020. Overall, the incidence of IBD was increase from 1.81 per 100,000 persons to 2.34 per 100,000 persons between 2016 and 2020. Overall, the prevalence rates of IBD was increase from 14.95 per 100,000 persons to 20.02 per 100,000 persons between 2016 and 2020. CONCLUSION: The epidemiological stages of IBD in Taiwan was considered in the acceleration in incidence stage, during which incidence rises and prevalence is relatively low. Understanding these geographical differences is important for the rising global burden of IBD.

Risk Factors of Carpal Tunnel Syndrome in Taiwan: A Population-Based Cohort Study.

BACKGROUND: Carpal tunnel syndrome (CTS), 1 of the most common peripheral neuropathies of the upper extremity, has been studied for decades regarding its epidemiology and associated medical conditions. We conducted a large-scale, age- and gender-matched study from an Asian population database to investigate the relationship between the incidence and the demographic characteristics. METHODS: A retrospective cohort study using data of National Health Insurance Research Database was conducted. One million enrollees in Taiwan was used to identify 9442 patients with CTS and 37,768 randomly selected controls, in a control-case ratio of 4:1. Diagnoses of CTS were ascertained from January 1, 2003, to December 31, 2012. Sociodemographic and medical characteristics were evaluated to assess the correlation with CTS. RESULTS: Annual incidence of CTS was approximately 0.4% during the 10-year-period in Taiwan, with higher incidence rate in female sex and middle age of group (50-59 years). Among the medical conditions, previous wrist injuries, obesity, gout, and rheumatoid arthritis were associated with CTS most significantly. CONCLUSIONS: Carpal tunnel syndrome has presented a relatively constant incidence in Taiwan. Female gender with middle age seemed to have the highest incident rate during a 10-year period from 2003 to 2012. Among the risk factors of CTS, previous wrist injuries, obesity, gout, and rheumatoid arthritis were demonstrated to be the most significantly correlated comorbidities.

Clinical outcomes and prognostic factors for prolonged mechanical ventilation in patients with acute stroke and brain trauma.

BACKGROUND/PURPOSE: Neurological dysfunction is a common condition necessitating prolonged mechanical ventilation (PMV). We investigated the clinical features and outcomes of patients with acute neurological diseases requiring PMV. METHODS: This retrospective observational study was conducted at the Respiratory Care Center (RCC) of Chang Gung Memorial Hospital, Taiwan, between January 2011 and January 2014. The main outcome was weaning success, defined as successful withdrawal from mechanical ventilator support for more than 5 days. RESULTS: The study included 103 patients with acute stroke and brain trauma receiving PMV. Weaning success was reported in 63 (61%) patients and weaning failure was reported in 40 (39%) patients. Patients in the weaning failure group were older and had a lower RCC Glasgow Coma Scale (GCS) score (6.0 vs 7.9, p = 0.005), lower albumin level (2.8 vs 3.1, p = 0.015), longer RCC stay (28.7 vs 21.3 days, p = 0.017), and higher in-hospital mortality rate (47% vs 9%, p < 0.01). Multivariate analysis revealed that reduced RCC GCS score is an independent prognostic factor for weaning failure (odds ratio [OR] = 1.22, 95% confidence interval [CI] = 1.05-1.46, p = 0.016) and that per unit increase of RCC GCS score is associated with a lower risk of in-hospital mortality (OR = 0.83, 95% CI = 0.70-0.96, p = 0.019). CONCLUSION: Reduced RCC GCS score is an independent prognostic factor for weaning failure, and is associated with increased in-hospital mortality rates in patients with acute stroke and brain trauma requiring PMV.

Whole genome sequencing identifies genetic variants associated with co-trimoxazole hypersensitivity in Asians.

BACKGROUND: Co-trimoxazole, a sulfonamide antibiotic, is used to treat a variety of infections worldwide, and it remains a common first-line medicine for prophylaxis against Pneumocystis jiroveci pneumonia. However, it can cause severe cutaneous adverse reaction (SCAR), including Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms. The pathomechanism of co-trimoxazole-induced SCAR remains unclear. OBJECTIVE: We aimed to investigate the genetic predisposition of co-trimoxazole-induced SCAR. METHODS: We conducted a multicountry case-control association study that included 151 patients with of co-trimoxazole-induced SCAR and 4631 population controls from Taiwan, Thailand, and Malaysia, as well as 138 tolerant controls from Taiwan. Whole-genome sequencing was performed for the patients and population controls from Taiwan; it further validated the results from Thailand and Malaysia. RESULTS: The whole-genome sequencing study (43 case patients vs 507 controls) discovered that the single-nucleotide polymorphism rs41554616, which is located between the HLA-B and MICA loci, had the strongest association with co-trimoxazole-induced SCAR (P = 8.2 × 10-9; odds ratio [OR] = 7.7). There were weak associations of variants in co-trimoxazole-related metabolizing enzymes (CYP2D6, GSTP1, GCLC, N-acetyltransferase [NAT2], and CYP2C8). A replication study using HLA genotyping revealed that HLA-B∗13:01 was strongly associated with co-trimoxazole-induced SCAR (the combined sample comprised 91 case patients vs 2545 controls [P = 7.2 × 10-21; OR = 8.7]). A strong HLA association was also observed in the case patients from Thailand (P = 3.2 × 10-5; OR = 3.6) and Malaysia (P = .002; OR = 12.8), respectively. A meta-analysis and phenotype stratification study further indicated a strong association between HLA-B∗13:01 and co-trimoxazole-induced drug reaction with eosinophilia and systemic symptoms (P = 4.2 × 10-23; OR = 40.1). CONCLUSION: This study identified HLA-B∗13:01 as an important genetic factor associated with co-trimoxazole-induced SCAR in Asians.

Disseminated intravascular coagulation in Stevens-Johnson syndrome and toxic epidermal necrolysis.

BACKGROUND: Patients with Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) have high mortality rates. Disseminated intravascular coagulation has been reported in SJS/TEN patients. The influence of this lethal complication in patients with SJS/TEN is not well known. OBJECTIVE: This study aimed to investigate the risk and outcomes of disseminated intravascular coagulation in patients with SJS/TEN. METHODS: We analyzed the disseminated intravascular coagulation profiles of patients receiving a diagnosis of SJS/TEN between 2010 and 2019. RESULTS: We analyzed 150 patients with SJS/TEN (75 with SJS, 22 with overlapping SJS/TEN, and 53 with TEN) and their complete disseminated intravascular coagulation profiles. Disseminated intravascular coagulation was diagnosed in 32 patients (21.3%), primarily those with TEN. It was significantly associated with systemic complications, including gastrointestinal bleeding, respiratory failure, renal failure, liver failure, infection, and bacteremia. Additionally, SJS/TEN patients with disseminated intravascular coagulation had elevated procalcitonin levels. Among patients with SJS/TEN, disseminated intravascular coagulation was associated with a greater than 10-fold increase in mortality (78.1% vs 7%). LIMITATIONS: The study limitations include small sample size and a single hospital system. CONCLUSION: Disseminated intravascular coagulation is a potential complication of SJS/TEN and associated with higher mortality. Early recognition and appropriate management of this critical complication are important for patients with SJS/TEN.

Incidence and Risk of Carpal Tunnel Syndrome in End-Stage Renal Disease Patients on Dialysis: A Nationwide Population-Based Matched Cohort Study.

Carpal tunnel syndrome (CTS) is a common cause of compression neuropathy of the upper extremities. This retrospective nationwide matched cohort study was conducted using the data from the Taiwan National Health Insurance Research Database between January 2003 and December 2012. The incidence rate of CTS was 975.84 and 544.12/100,000 person-years, respectively, yielding an incidence rate ratio of 1.79 (95% confidence interval, 1.68-1.91, P < 0.0001). CTS patients with End-stage renal disease (ESRD) in the dialysis group were more likely to receive surgical intervention than those the control group (62.41% vs 12.89%, P < 0.0001). The risk of CTS was significantly higher in the ESRD on dialysis cohort (10-year cumulative incidence, 8.0%) than in the control cohort (5.1%), which yielded an adjusted hazard ratio of 13.95 (95% confidence interval, 10.95-17.76, P < 0.0001). The high risk of CTS in ESRD patients on dialysis suggests that timely referral to hand surgeons with appropriate treatment should prevent permanent median nerve damage by CTS and may possibly improve patients' quality of life.

Saliva protein biomarkers to detect oral squamous cell carcinoma in a high-risk population in Taiwan.

Most cases of oral squamous cell carcinoma (OSCC) develop from visible oral potentially malignant disorders (OPMDs). The latter exhibit heterogeneous subtypes with different transformation potentials, complicating the early detection of OSCC during routine visual oral cancer screenings. To develop clinically applicable biomarkers, we collected saliva samples from 96 healthy controls, 103 low-risk OPMDs, 130 high-risk OPMDs, and 131 OSCC subjects. These individuals were enrolled in Taiwan's Oral Cancer Screening Program. We identified 302 protein biomarkers reported in the literature and/or through in-house studies and prioritized 49 proteins for quantification in the saliva samples using multiple reaction monitoring-MS. Twenty-eight proteins were successfully quantified with high confidence. The quantification data from non-OSCC subjects (healthy controls + low-risk OPMDs) and OSCC subjects in the training set were subjected to classification and regression tree analyses, through which we generated a four-protein panel consisting of MMP1, KNG1, ANXA2, and HSPA5. A risk-score scheme was established, and the panel showed high sensitivity (87.5%) and specificity (80.5%) in the test set to distinguish OSCC samples from non-OSCC samples. The risk score >0.4 detected 84% (42/50) of the stage I OSCCs and a significant portion (42%) of the high-risk OPMDs. Moreover, among 88 high-risk OPMD patients with available follow-up results, 18 developed OSCC within 5 y; of them, 77.8% (14/18) had risk scores >0.4. Our four-protein panel may therefore offer a clinically effective tool for detecting OSCC and monitoring high-risk OPMDs through a readily available biofluid.

Vascular injury during primary total knee arthroplasty: A nationwide study.

PURPOSE: To evaluate the incidence, risk factors, mortality, and complications of direct vascular injury (VI) in patients who underwent primary total knee arthroplasty (TKA) using data from a nationwide database. METHODS: Data were collected from the National Health Insurance Research Database of Taiwan. The study group included 111,497 patients who underwent TKA from January 2004 to December 2011. In total, 15 cases of direct VI were reported (VI group). We analyzed the incidence, risk factors, mortality, complications of direct VI and hospital stays between groups (VI group and non-VI group). RESULTS: Average incidence of VI was 13.74 per 100,000 person-years. No patient-dependent risk factors for VI were identified. Surgeons with low surgical volume highly correlated with incidence of VI (P < 0.05). 90-day mortality was significantly higher (33.3% vs. 0.37%) and length of hospital stay was significantly longer (19.43 days vs. 7.26 days) in the VI group than in the control group. In addition, incidence of periprosthetic joint infection, restenosis at the injury site, and limb loss were significantly higher in the VI group than in the control group. CONCLUSION: VI during primary TKA was associated with significantly higher incidence of periprosthetic joint infection, restenosis at the injury site, and limb loss, as well as higher 90-day mortality. Therefore, surgeons should be aware of VI during primary TKA, especially those with low surgical volume.

RESULTS OF MACULAR HOLE SURGERY: Evaluation Based on the International Vitreomacular Traction Study Classification.

PURPOSE: To evaluate the differences in anatomical and visual function changes after macular hole (MH) surgery using the International Vitreomacular Traction Study classification. METHODS: Patients who underwent vitrectomy and blood-assisted internal limiting membrane peeling because of MHs were enrolled in the present study. The patients were divided into three groups according to the sizes of their MHs (small: ≤250 µm, medium: >250 µm and ≤400 µm, and large: >400 µm). The effect of vitreomacular traction on the outcome was also analyzed. All the patients were followed for at least 12 months. The changes in best-corrected visual acuity and the outer retina at the foveal area were monitored using spectral-domain optical coherence tomography. RESULTS: A total of 146 eyes of 146 patients were enrolled. The patients with small MHs showed significantly better mean final visual acuity (mean: 20/58) than patients with large MHs (20/178, P < 0.05). There was no significant difference between patients with small- and medium-sized MHs (20/69). Longitudinal analysis showed that the presence of vitreomacular traction was related to a better restoration of the outer retinal structure and visual acuity. CONCLUSION: Patients with smaller MHs and vitreomacular adhesion had superior final visual acuity and better restoration of the outer retinal structure after MH surgery.

No Difference in Morbidity and Mortality After Total Joint Arthroplasty in Liver Transplant Recipients: A Propensity Score-Matched Analysis of a Nationwide, Population-Based Study Using Universal Healthcare Data.

BACKGROUND: Controversy remains regarding the outcomes after total joint arthroplasty (TJA) among patients with or without liver transplantation (LT). This study aimed at investigating the prevalence of TJA in patients after LT and comparing the morbidity and mortality with the non-LT group. METHODS: We conducted a nationwide, population-based study, with data extracted from a universal health insurance database, based on the International Classification of Disease, Ninth Revision, Clinical Modification. Patients who underwent TJAs between January 2001 and December 2014 were included. Patients who had bilateral TJAs or a TJA before LT were excluded. A total of 43 patients with LT and 350,337 patients without LT were included. The analysis was implemented using data from all patients and those matched by 1-to-10 propensity score matching. Multivariable logistic regression was used to control confounding variables. RESULTS: The prevalence of patients undergoing TJA after LT was 1.3% (43/3276). After propensity score matching, patients with LT were not associated with 30-day complications (adjusted odds ratio [aOR], 0.98; 95% confidence interval [CI], 0.93-1.03; P = .35), 30-day readmission rates (aOR, 0.93; 95% CI, 0.92-1.08; P = .87), 90-day complication rates (aOR, 0.95; 95% CI, 0.88-1.02; P = .16), 1-year infection rates (aOR, 1.04; 95% CI, 0.96-1.12; P = .35), reoperation rates (aOR, 1.06; 95% CI, 0.92-1.23; P = .41), or mortality (aOR, 0.91; 95% CI, 0.80-1.04; P = .18). CONCLUSION: The morbidity and mortality seem to be comparable whether TJA is performed in patients with or without LT. Methods for risk assessment would be feasible in liver transplant recipients.

Association of Varicose Veins With Incident Venous Thromboembolism and Peripheral Artery Disease.

Importance: Varicose veins are common but rarely associated with serious health risks. Deep venous thrombosis (DVT), pulmonary embolism (PE), and peripheral artery disease (PAD) are also vascular diseases but associated with serious systemic effects. Little is known about the association between varicose veins and the incidence of other vascular diseases including DVT, PE, and PAD. Objective: To investigate whether varicose veins are associated with an increased risk of DVT, PE, or PAD. Design, Setting, and Participants: A retrospective cohort study using claims data from Taiwan's National Health Insurance program. Patients aged 20 years and older with varicose veins were enrolled from January 1, 2001-December 31, 2013, and a control group of patients without varicose veins were matched by propensity score. Patients previously diagnosed with DVT, PE, or PAD were excluded. Follow-up ended December 31, 2014. Exposures: Presence of varicose veins. Main Outcomes and Measures: Incidence rates of DVT, PE, and PAD were assessed in people with and without varicose veins. Cox proportional hazards models were used to estimate relative hazards, with the control group as reference. Results: There were 212 984 patients in the varicose veins group (mean [SD] age, 54.5 [16.0] years; 69.3% women) and 212 984 in the control group (mean [SD] age, 54.3 [15.6] years; 70.3% women). The median follow-up duration was 7.5 years for DVT, 7.8 years for PE, and 7.3 years for PAD for patients with varicose veins, and for the control group, follow-up duration was 7.6 years for DVT, 7.7 years for PE, and 7.4 years for PAD. The varicose veins group had higher incidence rates than the control group for DVT (6.55 vs 1.23 per 1000 person-years [10 360 vs 1980 cases]; absolute risk difference [ARD], 5.32 [95% CI, 5.18-5.46]), for PE (0.48 for the varicose veins group vs 0.28 for the control group per 1000 person-years [793 vs 451 cases]; ARD, 0.20 [95% CI, 0.16-0.24]), and for PAD (10.73 for the varicose veins group vs 6.22 for the control group per 1000 person-years [16 615 vs 9709 cases]; ARD, 4.51 [95% CI, 4.31-4.71]). The hazard ratios for the varicose veins group compared with the control group were 5.30 (95% CI, 5.05-5.56) for DVT, 1.73 (95% CI, 1.54-1.94) for PE, and 1.72 (95% CI, 1.68-1.77) for PAD. Conclusions and Relevance: Among adults diagnosed with varicose veins, there was a significantly increased risk of incident DVT; the findings for PE and PAD are less clear due to the potential for confounding. Whether the association between varicose veins and DVT is causal or represents a common set of risk factors requires further research.

Acupuncture Therapy and Incidence of Depression After Stroke.

BACKGROUND AND PURPOSE: We investigated whether use of acupuncture within a 3-month poststroke period after hospital discharge is associated with reduced risk of depression. METHODS: This cohort study included 16 046 patients aged ≥18 years with an initial hospitalization for stroke during 2000 and 2012 in the claims database of a universal health insurance program. Patients who had received acupuncture therapies within 3 months of discharge were defined as acupuncture users (n=1714). All patients were followed up for incidence of depression until the end of 2013. We assessed the association between use of acupuncture and incidence of depression using Cox proportional hazards models in all subjects and in propensity score-matched samples consisting of 1714 pairs of users and nonusers. RESULTS: During the follow-up period, the incidence of depression per 1000 person-years was 11.1 and 9.7 in users and nonusers, respectively. Neither multivariable-adjusted Cox models (hazard ratio, 1.04; 95% confidence interval, 0.84-1.29) nor the propensity score-matching model (hazard ratio, 1.06; 95% confidence interval, 0.79-1.42) revealed an association between use of acupuncture and incidence of depression. CONCLUSIONS: In patients admitted to hospital for stroke, acupuncture therapy within 3 months after discharge was not associated with subsequent incidence of depression.

Predictive Factors for Additional ProGlide Deployment in Percutaneous Endovascular Aortic Repair.

PURPOSE: To evaluate outcomes and predictive factors for additional ProGlide device deployment in percutaneous endovascular aortic repair (PEVAR) with the preclose technique. MATERIALS AND METHODS: Clinical data of patients who underwent PEVAR with the preclose technique from February 2012 to January 2015 were retrospectively reviewed. A total of 268 patients (229 men, 39 women) who underwent PEVAR (thoracic endovascular aortic repair [TEVAR], n = 113; endovascular abdominal aortic repair [EVAR], n = 152; simultaneous TEVAR and EVAR, n = 3) with 418 femoral access sites were enrolled. The mean age of the patients was 69 years ± 14. Univariate and multivariate analyses were performed to identify predictive factors associated with additional ProGlide device deployment. RESULTS: Primary technical success with adequate hemostasis and two ProGlide devices was 87.6%, and 48 femoral arterial access sites (11.5%) required additional ProGlide device deployment. The secondary technical success rate was 99.0%. Four femoral access sites (1.0%) needed surgical repair. Anterior wall calcification near the arteriotomy increased the risk of additional ProGlide device deployment (adjusted odds ratio, 6.19; 95% confidence interval, 2.81-13.64; P < .001), whereas larger sheath size, common femoral artery (CFA) diameter, and depth from the skin to the arteriotomy did not. CONCLUSIONS: Additional ProGlide device deployment reduces the rate of surgical repair after primary hemostasis failure in PEVAR. Anterior CFA wall calcification is a significant predictor for additional ProGlide device deployment.

A tale of two systems: practice patterns of a single group of emergency medical physicians in Taiwan and China.

BACKGROUND: The quality of pediatric emergency care has been a major concern in health care. Following a series of health system reforms in China, it is important to do this assessment of pediatric emergency care, and to explore potential influences of health care system. This study aimed to compare practice differences in treating children with respiratory illnesses in two emergency department (ED) settings within different health care systems: China and Taiwan. METHODS: A pooled cross-sectional hospital-based study was conducted in two tertiary teaching hospitals in Xiamen, China and Keelung, Taiwan belong to the same hospital chain group. A team of 21 pediatricians rotated between the EDs of the two hospitals from 2009 to 2012. There were 109,705 ED encounters treated by the same team of pediatricians and 6596 visits were analyzed for common respiratory illnesses. Twelve quality measures in process and outcomes of asthma, bronchiolitis and croup were reported. Descriptive statistics and multiple logistic regression models were applied to assess. In order to demonstrate the robustness of our findings, we analyzed the data using an alternative modeling technique, multilevel modeling. RESULTS: After adjustment, children with asthma presented to the ED in China had a significantly 76% lower likelihood to be prescribed a chest radiograph, and a 98% lower likelihood to be prescribed steroids and discharged home than those in Taiwan. Also, children with asthma presented to the ED in China had significantly 7.76 times higher risk to incur 24-72 h return visits. Furthermore, children with bronchiolitis in China (Odds ratio (OR): 0.21; 95% Confidence interval (CI): 0.17-0.28) were significantly less likely to be prescribed chest radiograph, but were significantly more likely to be prescribed antibiotics (OR: 2.19; 95% CI: 1.46-3.28). CONCLUSIONS: This study illustrated that although high quality care depends on better assessment of physician performance, the delivery of pediatric emergency care differed significantly between these two healthcare systems after holding the care providers the same and adjusting for important patient characteristics. The findings suggest that the features of the health care system may play a significant role.

Utility of (18)F-FDG PET/CT in patients with advanced squamous cell carcinoma of the uterine cervix receiving concurrent chemoradiotherapy: a parallel study of a prospective randomized trial.

PURPOSE: The aim of this prospective study was to assess the usefulness of (18)F-FDG PET/CT performed before and during treatment for predicting treatment failure in patients with advanced squamous cell carcinoma of the uterine cervix treated with concurrent chemoradiotherapy (CCRT). METHODS: Patients with cervical squamous cell carcinoma, International Federation of Gynecology and Obstetrics stage III/IVA or positive pelvic or paraaortic lymph node (LN) metastasis without other distant metastasis on PET/CT entering a randomized trial of CCRT (AGOG 09-001) were eligible. PET/CT scans were performed at baseline, during week 3 of CCRT and 2 - 3 months after CCRT. PET/CT parameters were correlated with sites of failure and overall survival (OS). The resulting predictors developed from the study cohort were validated on two independent datasets using area under the curve values, sensitivities and specificities. RESULTS: With a median follow-up of 54 months for survivors, 20 (36 %) of the 55 eligible patients were proven to have treatment failure. Sites of failure were local in five, regional in 11, and distant in 11. Four predictors for local failure, three for regional failure, and four for distant failures were identified. After validation with two independent cohorts of 31 and 105 patients, we consider the following as clinically useful predictors: pretreatment metabolic tumour volume (MTV) and during-treatment cervical tumour MTV for local failure; during-treatment SUVnode (maximum standardized uptake value of LNs) for regional and distant failure, and during-treatment MTV for distant failure. During-treatment SUVnode (P = .001) and cervical tumour MTVratio (P = .004) were independent significant predictors of OS by stepwise Cox regression. CONCLUSION: PET/CT imaging before and during treatment is useful for predicting failure sites and OS, making tailored therapeutic modifications feasible with potential outcome improvement during primary therapy.

Risk factors associated with the development of retinopathy 10 yr after the diagnosis of juvenile-onset type 1 diabetes in Taiwan: a cohort study from the CGJDES.

BACKGROUND: The aim of this study was to examine risk factors associated with the development of diabetic retinopathy (DR) 10 yr after the diagnosis of juvenile-onset type 1 diabetes in Taiwan. METHODS: This retrospective cohort study of 153 individuals with type 1 diabetes for >10 yr duration (mean duration: 13.1 yr) included participants in the Chang Gung Juvenile Diabetes Eye Study. Risk factors assessed for association with DR included age, gender, age at onset and duration of diabetes, self-reported smoking, blood pressure, lipid profile, urinalysis, glycated hemoglobin (HbA1c), body mass index, spherical equivalent, and axial length of the eyeball. RESULTS: There were 128 patients without DR and 25 patients with DR. The mean age at onset was 7.0 ± 4.0 yr (mean ± standard deviation). Cox proportional-hazards analysis showed that older-onset age (p = 0.001), higher HbA1c (p = 0.013), and higher triglyceride concentration (p = 0.015) were the strongest correlates of DR after adjustment for diabetes duration. CONCLUSIONS: Development of retinopathy 10 yr after diagnosis in people with juvenile-onset type 1 diabetes was associated with older onset age, higher HbA1c, and higher triglyceride concentration.

Chest Wall Constriction after the Nuss Procedure Identified from Chest Radiograph and Multislice Computed Tomography Shortly after Removal of the Bar.

BACKGROUND: This study radiographically examined the changes in the chest walls of patients with pectus excavatum (PE) after Nuss bar removal, to define the deformation caused by the bar and stabilizer. In the first part of the study, we compared the changes in chest radiographs of patients with PE to a preoperation PE control group. In the second part, we used multislice computed tomography (CT) scans to provide three-dimensional reconstructions with which to evaluate the changes to the thoracic wall. METHODS: Part 1 From June 2006 to August 2011, 1,125 patients with PE who had posteroanterior chest radiographs taken before undergoing the Nuss procedure at four hospitals were enrolled as a preoperative control group. At the same time, 203 patients who had the bar removed were enrolled as the study group. The maximum dimensions of the outer boundary of the first to ninth rib pairs (R1-R9, rib pair width), chest height, and chest width were measured. Part 2 Thirty-one consecutive patients with PE (20 males and 11 females) who underwent Nuss bar removal were evaluated 7 to 30 days after operation. During this period, a further 34 patients with PE who had undergone CT imaging before bar insertion were evaluated and compared with the postoperative group. RESULTS: Part 1 The width of the lower ribs (R4-R9) after bar removal was significantly less than in the age-matched controls. The ribs adjacent to the bar (R5-R7) showed the greatest restriction. The width of the upper ribs (R1-R3) 2 to 3 years after bar placement did not differ significantly from the controls. Patients who were operated on after 10 years of age had less of a restrictive effect. Three years of bar placement resulted in more restriction than a 2-year period, particularly in patients younger than 10 years old. Part 2: A significant constriction of the chest wall was observed in 13 patients after removal of the Nuss bar. Constriction at ribs 5 to 8 was found to be present adjacent to the site of bar insertion. However, constriction of the chest wall was found in only 3 of the 34 patients in the preoperative group. The severity of constriction (as graded by the spline model) also increased in the postoperative group. CONCLUSION: The growth of the chest wall was restricted after placement of the Nuss bar for PE correction. Long-term follow-up of chest wall growth is needed to clarify whether such constriction resolves with time.

Self-sampling HPV test in women not undergoing Pap smear for more than 5 years and factors associated with under-screening in Taiwan.

BACKGROUND/PURPOSE: Under-utilization of Papanicolaou (Pap) smear causes a gap in the prevention of cervical neoplasms. A prospective population-based study was conducted investigating whether a self-sampling human papillomavirus (HPV) test was feasible for under-users of Pap smear and factors associated with under-screening in Taiwan. METHODS: Women not having Pap smear screening for > 5 years were invited to participate in this study. Invitation letters and educational brochures were mailed to 4% of randomly selected eligible women from Taoyuan City, Taiwan, and responders received an HPV self-sampling kit. Those with HPV-positive results were recalled for a Pap smear and colposcopy. RESULTS: Between March 2010 and June 2012, 10,693 women were invited, 354 responded (3.3%), and 282 (2.6%) gave valid informed consent, answered the questionnaire, and submitted HPV samples. The median age of enrolled women was 48.1 years. Forty-seven women (16.7%) had a positive HPV test, and 14 women accepted further survey to find two CIN2+. Another two cases of CIN2+ were identified from a national registry database. The cost of direct mailing self-samplers was less than that done on request (from NT$434,866 to NT$164,229, response rate of 5% to 15%, respectively, versus NT$683,957 for detecting 1 CIN2+). Reasons for not attending screening included lack of time, embarrassment, assumed low risk, fear of positive results, and perceived potential pain. Among the responders, 90.8% found the method acceptable. CONCLUSION: Our study indicated that different approaches (e.g., direct mailing self-samplers to under-users and/or various educational interventions) must be explored to improve coverage in populations with culture characteristics similar to Taiwan.