Wen-Yao Yin

Adjusted Age-Adjusted Charlson Comorbidity Index Score as a Risk Measure of Perioperative Mortality before Cancer Surgery

Background Identification of patients at risk of death from cancer surgery should aid in preoperative preparation. The purpose of this study is to assess and adjust the age-adjusted Charlson comorbidity index (ACCI) to identify cancer patients with increased risk of perioperative mortality. Methods We identified 156,151 patients undergoing surgery for one of the ten common cancers between 2007 and 2011 in the Taiwan National Health Insurance Research Database. Half of the patients were randomly selected, and a multivariate logistic regression analysis was used to develop an adjusted-ACCI score for estimating the risk of 90-day mortality by variables from the original ACCI. The score was validated. The association between the score and perioperative mortality was analyzed. Results The adjusted-ACCI score yield a better discrimination on mortality after cancer surgery than the original ACCI score, with c-statics of 0.75 versus 0.71. Over 80 years of age, 70–80 years, and renal disease had the strongest impact on mortality, hazard ratios 8.40, 3.63, and 3.09 (P < 0.001), respectively. The overall 90-day mortality rates in the entire cohort varied from 0.9%, 2.9%, 7.0%, and 13.2% in four risk groups stratifying by the adjusted-ACCI score; the adjusted hazard ratio for score 4–7, 8–11, and ≥ 12 was 2.84, 6.07, and 11.17 (P < 0.001), respectively, in 90-day mortality compared to score 0–3. Conclusions The adjusted-ACCI score helps to identify patients with a higher risk of 90-day mortality after cancer surgery. It might be particularly helpful for preoperative evaluation of patients over 80 years of age.

Risk of Rheumatoid Arthritis in Patients with Type 2 Diabetes: A Nationwide Population-Based Case-Control Study

Objective Type 2 diabetes is associated with chronic, low-grade inflammation and could potentially trigger the progression of other, more prominent inflammatory diseases such as rheumatoid arthritis (RA). Therefore, we aimed to investigate the risk of incident RA in Taiwanese patients with type 2 diabetes using a population-based health claims database. Methods This nationwide, population-based, case-control study used administrative data to identify 1,416 patients with RA (age ≥20 years) as cases and 7,080 controls that were frequency-matched for sex, 10-year age group, and year of catastrophic illness certificate application date (index year). All subjects were retrospectively traced back, up to 13 years prior to the index year, for their first diagnosis of type 2 diabetes. Logistic regression analysis was conducted to quantify the association between incident RA and type 2 diabetes. Results The odds of developing RA were significantly higher in female (odds ratio [OR] 1.46, 95% confidence interval [95% CI] 1.24–1.72) but not in male (OR 1.00, 95% CI 0.72–1.37) patients who had previously diagnosed with type 2 diabetes. Subgroup analysis indicated that the odds of developing RA were more prominent in younger females (20 to 44 years of age) with type 2 diabetes. In addition, the odds of developing RA in female patients with type 2 diabetes were higher in those with a shorter time interval between the diagnosis of type 2 diabetes and RA. Conclusions This large nationwide, population-based, case-control study showed an elevated risk of RA in female Taiwanese patients with type 2 diabetes. Our findings were consistent with the hypothesis that chronic low-grade inflammation in type 2 diabetes may elicit the development of RA in genetically susceptible individuals.

Increased risk of primary Sjogren's syndrome in female patients with thyroid disorders: a longitudinal population-based study in Taiwan.

Background A number of reports have indicated an association between thyroid diseases and primary Sjögrens syndrome (pSS). However, fewer studies have investigated whether the presence of thyroid diseases is associated with increased risk of developing pSS. Thus, the aim of our study was to use a nationwide health claims database to explore the prevalence and risk of pSS in female patients with thyroid diseases. Methods From the Registry of Catastrophic Illness database in the National Health Insurance Research Database in Taiwan, we identified 389 female patients with a diagnosis of pSS from 2005 to 2010. We also obtained 1945 control subjects frequency-matched on sex, 10-year age interval, and year of index date from the Longitudinal Health Insurance Database (LHID2000). Both groups were retrospectively traced back to a period of eight years to obtain diagnosis of thyroid diseases prior to index date. Results A significantly higher risk of pSS was associated with the presence of thyroid diseases (adjusted odds ratio (AOR) = 2.1, 95% confidence interval (CI) = 1.6–2.9). Among the sub-categories of thyroid diseases, patients with thyroiditis (AOR = 3.6, 95% CI = 1.7–7.5), thyrotoxicosis (AOR = 2.5, 95% CI = 1.6–3.8), and unspecified hypothyroidism (AOR = 2.4, 95% CI = 1.2–4.6), and simple and unspecified goiter (AOR = 2.0, 95% CI = 1.3–3.3) were significantly associated with increased risk of pSS. The associations were generally stronger in the mid-forties to mid-sixties age group, except in patients with unspecified hypothyroidism. Conclusions The risk of pSS was significantly increased in female patients with thyroid diseases, particularly those in their mid-forties to mid-sixties. An increased awareness of the possibility of pSS in perimenopausal females with thyroid diseases is important to preserve their quality of life and to avoid comorbidity.

Anti-citrullinated protein antibodies activated ERK1/2 and JNK mitogen-activated protein kinases via binding to surface-expressed citrullinated GRP78 on mononuclear cells.

In a previous study, we found that anti-citrullinated protein antibodies (ACPAs) enhance nuclear factor (NF)-κB activity and tumor necrosis factor (TNF)-α production by normal human peripheral blood mononuclear cells (PBMCs) and U937 cells via binding to surface-expressed citrullinated glucose-regulated protein 78 (cit-GRP78). However, the downstream signaling pathways remain unclear after binding. In the present study, we firstly measured the effects of different kinase inhibitors on ACPA-mediated TNF-α production from normal PBMCs and monocytes. Then, the native and phosphorylated mitogen-activated protein kinases (MAPKs) were detected in ACPA-activated U937 cells by Western blotting. We also explored the role of the phosphoinositide 3-kinase (PI3K)-Akt pathway in activating IκB kinase alpha (IKK-α) in ACPA-stimulated U937 cells. Finally, we measured the amount of cit-GRP78 from PBMC membrane extracts in RA patients and controls. We found that MAPK and Akt inhibitors, but not PI3K inhibitor, remarkably suppressed ACPA-mediated TNF-α production. Interestingly, ACPAs selectively activated extracellular signal-regulated kinase 1/2 (ERK1/2) and c-jun N-terminal kinase (JNK), but not p38 MAPK, in U937 cells. This activation was suppressed by cit-GRP78, but not GRP78. The JNK activation further enhanced the phosphorylation of Akt and IKK-α. The expression of cit-GRP78 on cell membrane was higher in RA than normal PBMCs. Taken together; these results suggest that through binding to surface, over-expressed cit-GRP78 on RA PBMCs, ACPAs selectively activate ERK1/2 and JNK signaling pathways to enhance IKK-α phosphorylation, which leads to the activation of NF-κB and the production of TNF-α .

Increased prevalence of polyomavirus BK viruria that correlates with thrombocytopenia in patients with systemic lupus erythematosus on intensive immunosuppressive therapy

The prevalence of polyomavirus BK (BKV) reactivation is high in patients with systemic lupus erythematosus (SLE) on long-term immunosuppressants compared to normal population. However, only a few studies are available for the possible correlation of BKV reactivation and clinical manifestations in SLE patients. In the present study, we tried to correlate BKV viruria, clinical manifestations, laboratory findings, and medications in patients with SLE. The urine BKV viral DNA copies were detected from 95 patients with SLE and 32 healthy volunteers by real-time PCR. We found that the prevalence rate of BKV viruria in SLE patients was significantly higher than normal group (71.6% vs. 18.6%, p < 0.001) as well as the urine BKV DNA viral load (4.74 ± 3.17 vs. 1.08 ± 2.33 by log scale, p < 0.001). Interestingly, BKV viruria (+) SLE patients had more thrombocytopenic events than BKV viruria ( − ) group (32.4% vs. 3.7%, p = 0.008 after adjustment by age and sex). The patients with BKV viruria DNA copy number >3,200,000/ml exhibited more thrombocytopenia risk than BKV viruria ≦3,200,000 copy number/ml or BKV viruria ( − ). The use of potent immunosuppressants may increase BKV viruria. In a refractory thrombocytoponeic case, the add-on of anti-BKV medication, leflunomide 20 mg/day rapidly decreased BKV viruria and recovered platelet counts. In conclusion, our study demonstrated that patients with SLE had higher prevalence rate of BKV reactivation that is correlated with thrombocytopenic episode. Intensive immunosuppressive therapy in SLE may increase the risk of BKV viruria.

The combined effects of hospital and surgeon volume on short-term survival after hepatic resection in a population-based study.

Background The influence of different hospital and surgeon volumes on short-term survival after hepatic resection is not clearly clarified. By taking the known prognostic factors into account, the purpose of this study is to assess the combined effects of hospital and surgeon volume on short-term survival after hepatic resection. Methods 13,159 patients who underwent hepatic resection between 2002 and 2006 were identified in the Taiwan National Health Insurance Research Database. Data were extracted from it and short-term survivals were confirmed through 2006. The Cox proportional hazards model was used to assess the relationship between survival and different hospital, surgeon volume and caseload combinations. Results High-volume surgeons in high-volume hospitals had the highest short-term survivals, following by high-volume surgeons in low-volume hospitals, low-volume surgeons in high-volume hospitals and low-volume surgeons in low-volume hospitals. Based on Cox proportional hazard models, although high-volume hospitals and surgeons both showed significant lower risks of short-term mortality at hospital and surgeon level analysis, after combining hospital and surgeon volume into account, high-volume surgeons in high-volume hospitals had significantly better outcomes; the hazard ratio of other three caseload combinations ranging from 1.66 to 2.08 (p<0.001) in 3-month mortality, and 1.28 to 1.58 (p<0.01) in 1-year mortality. Conclusions The combined effects of hospital and surgeon volume influenced the short-term survival after hepatic resection largely. After adjusting for the prognostic factors in the case mix, high-volume surgeons in high-volume hospitals had better short-term survivals. Centralization of hepatic resection to few surgeons and hospitals might improve patients’ prognosis.

A correlation between polyomavirus JC virus quantification and genotypes in renal transplantation

OBJECTIVE To determine whether the John Cunningham virus (JCV) viral load and the multigenotypes in viruria are correlated with transplant patients. METHODS The urine of 60 renal transplant patients and 60 healthy controls were screened. We used quantitative real-time polymerase chain reaction and capillary electrophoresis to assess viral load and genotype respectively. RESULTS The incidence of viruria and viral load were higher in transplant patients with P = .0092 and P = .0094, respectively. The incidence of different genotype in transplant patients versus controls was 8.3% versus 13.3% for single genotype, 26.7% versus 5% for 2 genotypes, and 5% versus 0% for multigenotypes (P = .0004). The incidence of more than 2 genotypes was high in people with a high viral load and closely related with the transplant patients (P = .007). CONCLUSIONS Not only viral load but also genotypes are important as a screening parameter to understand the immune milieu of the patients to prevent subsequent complications like polyomavirus nephropathy, infection, and malignancy.

BK virus as a potential oncovirus for bladder cancer in a renal transplant patient

Renal transplant patients have high risk for bladder cancer. The reactivation of BK virus is common in renal transplant patients especially in the urinary tract. There was some evidence suggesting that the reactivation of BK virus (BKV) in renal transplant patients may associate with the development of bladder cancer. Here we demonstrated that a patient that had persistent elevated BKV viruria (urine BKV DNA concentration more than 10(11) copies/ml) after renal transplantation. Then, bladder cancer was found in 13 months after kidney transplantation. The urine BKV DNA concentration was detected by real-time PCR and the BKV DNA in the bladder tumor was detected by PCR. BKV DNA was found in the marginal and central part of the bladder tumor. After removal of the bladder cancer, the urine BKV viral load in this patients dropped dramatically to <10(2) copies/ml. However, the urine viral load had increased modestly to 10(6) copies/ml in 3 months after surgery. Since there is a close correlation between the urine BK viral load and the presence of bladder cancer, we suggested that there might be a causal relationship between the reactivation of BKV and the development of bladder cancer in renal transplant patient.

The safety and adequacy of resection on hepatocellular carcinoma larger than 10 cm: A retrospective study over 10 years

Background/purpose Current treatment options for HCC≥10 cm (huge HCC) are limited. Otherwise, the margin status is known as a prognostic factor. Our aim was to determine the safety, effectiveness, and risk factors for overall survival and disease-free survival for these patients. Methods A total of 211 consecutive patients from 2000/08 to 2010/12 were enrolled. Characteristics of patients, tumors, and treatment were compared between the huge group (HCCs; ≥10 cm, n = 23; 11%) and those with smaller group (HCC; <10 cm n = 188; 89%). Disease-free survival (DFS), overall survival (OS), and risk factors were analyzed. Results Median follow up was 37 months. Patients with huge HCC were more likely to be symptomatic, positive for preoperative portal vein thrombosis, longer surgical time, more blood loss and transfusions, and significantly shorter median OS and DFS. Both groups had similar postoperative mortality and morbidity rates. In the huge HCC, multivariate analysis identified two significant determinants of DFS (preoperative portal vein thrombosis on imaging and tumor-free margin less than 1 mm) and two significant determinants of OS (age over 80 and preoperative portal vein thrombosis). Even with positive margins, it still had no impact on OS. For DFS, 1 mm free margins appeared to be adequate. Conclusion Tumor-free margin is an independent risk factor for recurrence but has no impact on OS. Surgical margin >1 mm is adequate in patients with tumors ≥10 cm. Postoperative close follow up, especially of distant metastasis, and appropriate treatment of recurrence by a multidisciplinary approach may improve prognosis.

Donor-derived Cryptococcus infection in liver transplant: case report and literature review.

Cryptococcosis occurring within 30 days after transplant is unusual. We present a case of cryptococcosis diagnosed within 2 weeks of liver transplant and cryptococcal infection transmitted by liver transplant is considered as the cause. A 63-year-old woman with hepatitis C virus-related cirrhosis and hepatocellular carcinoma had an orthotopic liver transplant from a 45-year-old donor. The immediate postoperative course was smooth, although she was confused with a fever, tachycardia, respiratory failure of 1 weeks duration after the orthotopic liver transplant. A liver biopsy was performed for hyperbilirubinemia 2 weeks after the orthotopic liver transplant that showed a Cryptococcus-like yeast. Her blood culture was reexamined, and it was confirmed as Cryptococcus neoformans that had been misinterpreted as candida initially. At the time of the re-examination, her sputum was clear. We checked her preoperative blood sample, retrospectively, for serum cryptococcal antigen with negative result. She was on liposomal amphotericin treatment for 1 month when her blood culture became negative. She was discharged home, with good liver function and a low antigen titer for cryptococcal infection. Cryptococcal disease usually develops at a mean of 5.6 months after transplant. However an early occurrence is rare. Apart from that, its variable clinical presentations make early detection difficult. It might be an early reactivation or a donor-derived infection. The latter usually occurs in unusual sites (eg, the transplanted organ as the sole site of involvement). Our case presented as cryptococcoma and liver involvement was diagnosed by an unintentional liver biopsy.