Clinicopathological characteristics of myelodysplastic syndromes with del(5q) in Taiwan.

BACKGROUND: Myelodysplastic syndromes (MDS) are a group of clonal haematopoietic stem cell disorders characterised by ineffective haematopoiesis and cytopenia. Studies have reported differences in MDS between Asian and Western countries, but data from Taiwan are scarce. MATERIALS AND METHODS: In this study we analysed the clinical and pathological features of 32 Taiwanese MDS patients with del(5q) (ie, del(5q) alone [Group A, n = 11], del(5q) with one additional cytogenetic abnormality other than monosomy 7 or del(7q) [Group B, del(5q)+1; n = 6], and del(5q) with ≥2 additional cytogenetic abnormalities [Group C, n = 15]). RESULTS: Progression-free survival (PFS) and overall survival (OS) were more favourable for Group A than for Groups B (p < 0.05) and C (p ≤ 0.001). Multivariate analysis showed that age >70 years, thrombocytopenia, and karyotype other than del(5q) alone were poor prognostic factors. Among the patients that had World Health Organization (WHO)-defined MDS with isolated del(5q), one patient (9%) had a typical marrow morphology of 5q minus syndrome with erythroid hypoplasia and four patients (36%) had hypolobated megakaryocytes. In addition, PFS and OS were significantly more favorable for the patients with del(5q) alone than for those with del(5q)+1 (p < 0.05). CONCLUSION: The bone marrow morphology, clinical features, and prognosis of Taiwanese MDS patients with del(5q) were different from those associated with MDS with isolated del(5q) as defined in the current WHO classification. Researchers should compare different geographic regions and racial populations to determine whether geographic and racial differences exist with respect to MDS with del(5q).

COVID-19 vaccination and breakthrough infections in patients with cancer.

BACKGROUND: Vaccination is an important preventive health measure to protect against symptomatic and severe COVID-19. Impaired immunity secondary to an underlying malignancy or recent receipt of antineoplastic systemic therapies can result in less robust antibody titers following vaccination and possible risk of breakthrough infection. As clinical trials evaluating COVID-19 vaccines largely excluded patients with a history of cancer and those on active immunosuppression (including chemotherapy), limited evidence is available to inform the clinical efficacy of COVID-19 vaccination across the spectrum of patients with cancer. PATIENTS AND METHODS: We describe the clinical features of patients with cancer who developed symptomatic COVID-19 following vaccination and compare weighted outcomes with those of contemporary unvaccinated patients, after adjustment for confounders, using data from the multi-institutional COVID-19 and Cancer Consortium (CCC19). RESULTS: Patients with cancer who develop COVID-19 following vaccination have substantial comorbidities and can present with severe and even lethal infection. Patients harboring hematologic malignancies are over-represented among vaccinated patients with cancer who develop symptomatic COVID-19. CONCLUSIONS: Vaccination against COVID-19 remains an essential strategy in protecting vulnerable populations, including patients with cancer. Patients with cancer who develop breakthrough infection despite full vaccination, however, remain at risk of severe outcomes. A multilayered public health mitigation approach that includes vaccination of close contacts, boosters, social distancing, and mask-wearing should be continued for the foreseeable future.

Accurate quantification of phosphorus intergranular segregation in iron by STEM-EDX.

This study describes a method to quantify phosphorus grain boundary segregation by Energy Dispersive X-ray Spectroscopy in Scanning Transmission Electron Microscope (STEM-EDX). A "box-type method" is employed, removing the long-discussed problems of interaction volume and the beam broadening effect. The proposed methodology also introduces a novel way of subtracting the spectrum background to remove the influence of coherent Bremsstrahlung and spurious peaks. A Fe-P model alloy was used to compare the box method to the quantification results previously obtained by atom probe tomography on two high angle grain boundaries. The results are specifically reported in surface concentration (atom/nm2) to avoid additional hypotheses and allow the results between the two techniques to be directly compared. The measurements show that the box-type method can accurately measure phosphorus intergranular segregation in iron.

Association of clinical factors and recent anticancer therapy with COVID-19 severity among patients with cancer: a report from the COVID-19 and Cancer Consortium.

BACKGROUND: Patients with cancer may be at high risk of adverse outcomes from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We analyzed a cohort of patients with cancer and coronavirus 2019 (COVID-19) reported to the COVID-19 and Cancer Consortium (CCC19) to identify prognostic clinical factors, including laboratory measurements and anticancer therapies. PATIENTS AND METHODS: Patients with active or historical cancer and a laboratory-confirmed SARS-CoV-2 diagnosis recorded between 17 March and 18 November 2020 were included. The primary outcome was COVID-19 severity measured on an ordinal scale (uncomplicated, hospitalized, admitted to intensive care unit, mechanically ventilated, died within 30 days). Multivariable regression models included demographics, cancer status, anticancer therapy and timing, COVID-19-directed therapies, and laboratory measurements (among hospitalized patients). RESULTS: A total of 4966 patients were included (median age 66 years, 51% female, 50% non-Hispanic white); 2872 (58%) were hospitalized and 695 (14%) died; 61% had cancer that was present, diagnosed, or treated within the year prior to COVID-19 diagnosis. Older age, male sex, obesity, cardiovascular and pulmonary comorbidities, renal disease, diabetes mellitus, non-Hispanic black race, Hispanic ethnicity, worse Eastern Cooperative Oncology Group performance status, recent cytotoxic chemotherapy, and hematologic malignancy were associated with higher COVID-19 severity. Among hospitalized patients, low or high absolute lymphocyte count; high absolute neutrophil count; low platelet count; abnormal creatinine; troponin; lactate dehydrogenase; and C-reactive protein were associated with higher COVID-19 severity. Patients diagnosed early in the COVID-19 pandemic (January-April 2020) had worse outcomes than those diagnosed later. Specific anticancer therapies (e.g. R-CHOP, platinum combined with etoposide, and DNA methyltransferase inhibitors) were associated with high 30-day all-cause mortality. CONCLUSIONS: Clinical factors (e.g. older age, hematological malignancy, recent chemotherapy) and laboratory measurements were associated with poor outcomes among patients with cancer and COVID-19. Although further studies are needed, caution may be required in utilizing particular anticancer therapies. CLINICAL TRIAL IDENTIFIER: NCT04354701.

Caries Risk Prediction Models in a Medical Health Care Setting.

Despite development of new technologies for caries control, tooth decay in primary teeth remains a major global health problem. Caries risk assessment (CRA) models for toddlers and preschoolers are rare. Among them, almost all models use dental factors (e.g., past caries experience) to predict future caries risk, with limited clinical/community applicability owing to relatively uncommon dental visits compared to frequent medical visits during the first year of life. The objective of this study was to construct and evaluate risk prediction models using information easily accessible to medical practitioners to forecast caries at 2 and 3 y of age. Data were obtained from the Growing Up in Singapore Towards Healthy Outcomes (GUSTO) mother-offspring cohort. Caries was diagnosed using modified International Caries Detection and Assessment System criteria. Risk prediction models were constructed using multivariable logistic regression coupled with receiver operating characteristic analyses. Imputation was performed using multiple imputation by chained equations to assess effect of missing data. Caries rates at ages 2 y (n = 535) and 3 y (n = 721) were 17.8% and 42.9%, respectively. Risk prediction models predicting overall caries risk at 2 and 3 y demonstrated area under the curve (AUC) (95% confidence interval) of 0.81 (0.75-0.87) and 0.79 (0.74-0.84), respectively, while those predicting moderate to extensive lesions showed 0.91 (0.85-0.97) and 0.79 (0.73-0.85), respectively. Postimputation results showed reduced AUC of 0.75 (0.74-0.81) and 0.71 (0.67-0.75) at years 2 and 3, respectively, for overall caries risk, while AUC was 0.84 (0.76-0.92) and 0.75 (0.70-0.80), respectively, for moderate to extensive caries. Addition of anterior caries significantly increased AUC in all year 3 models with or without imputation (all P < 0.05). Significant predictors/protectors were identified, including ethnicity, prenatal tobacco smoke exposure, history of allergies before 12 mo, history of chronic maternal illness, maternal brushing frequency, childbearing age, and so on. Integrating oral-general health care using medical CRA models may be promising in screening caries-susceptible infants/toddlers, especially when medical professionals are trained to "lift the lip" to identify anterior caries lesions.

Association of fine-particulate and acidic-gas air pollution with premenstrual syndrome risk.

OBJECTIVE: Air pollution had been reported to be associated with the reproductive health of women. However, the association of particulate matter (PM) and acid gases air pollution with premenstrual syndrome (PMS) warrants investigation. This study investigated the effects of air pollution on PMS risk. POPULATION: We combined data from the Taiwan Air Quality-Monitoring Database and the Longitudinal Health Insurance Database. In total, an observational cohort of 85 078 Taiwanese women not diagnosed as having PMS. METHODS: Air pollutant concentrations were grouped into four levels based on the concentration quartiles of several types of air pollutants. MAIN OUTCOME MEASURES: We then applied univariable and multivariable Cox proportional hazard regression models to assess PMS risk in association with each pollutant type. RESULTS: Women exposed to Q4-level SO2 exhibited a 7.77 times higher PMS risk compared with those to Q1-level SO2 (95% confidence interval [CI] = 6.22-9.71). Women exposed to Q4-level NOx exhibited a 2.86 times higher PMS risk compared with those exposed to Q1-level NOx (95% CI = 2.39-3.43). Women exposed to Q4-level NO exhibited a 3.17 times higher PMS risk compared with women exposed to Q1-level NO (95% CI = 2.68-3.75). Finally, women exposed to Q4-level PM with a ≤2.5-µm diameter (PM2.5) exhibited a 3.41 times higher PMS risk compared with those exposed to Q1-level PM2.5 (95% CI = 2.88-4.04). CONCLUSIONS: High incidences of PMS were noted in women who lived in areas with higher concentrations of SO2, NOx, NO, NO2 and PM2.5.

Efficacy and safety of high-dose vs low-dose leucovorin in patients with colorectal cancer: systematic review and meta-analysis.

AIM: The clinical benefits of a combination of leucovorin and fluorouracil have been established in the treatment of colorectal cancer. Due to a leucovorin shortage in 2008, many institutions revised their protocols to reduce the dose of leucovorin. After the shortage was resolved, some hospitals still maintained their modified protocols. Thus, we conducted a systematic review to evaluate the efficacy and safety of low- vs high-dose leucovorin in the treatment of colorectal cancer. METHOD: The PubMed, Embase and Cochrane databases were searched for studies published before May 2019. The meta-analysis was performed to estimate the pooled effect sizes by using a random effect model. The primary outcomes were median survival time and tumour response rate. Secondary outcomes were haematological and nonhaematological toxicities. RESULTS: Eight randomized controlled trials and four retrospective studies were reviewed. The pooled median survival time was similar between the two dose levels (standard mean difference -0.06, 95% CI -0.19 to 0.08). The pooled tumour response rate was comparatively higher in the high-dose leucovorin regimen (OR 0.81; 95% CI 0.55-1.18). No statistically significant difference was found between the haematological and nonhaematological toxicities of the two groups. However, there were fewer diarrhoea events in the low-dose leucovorin regimen. CONCLUSION: Low-dose leucovorin regimens seemed feasible approaches for colorectal cancer treatment when the shortage happened, because both regimens manifested comparable outcomes in survival time and tumour response rate.

Mechanisms of ischaemic neural progenitor proliferation: a regulatory role of the HIF-1α-CBX7 pathway.

AIMS: Investigations of the molecular mechanisms of hypoxia- and ischaemia-induced endogenous neural progenitor cell (NPC) proliferation have mainly focused on factors secreted in response to environmental cues. However, little is known about the intrinsic regulatory machinery underlying the self-renewing division of NPCs in the brain after stroke. METHODS AND RESULTS: Polycomb repressor complex 1-chromobox7 (CBX7) has emerged as a key regulator in several cellular processes including stem cell self-renewal and cancer cell proliferation. The hypoxic environment triggering NPC self-renewal after CBX7 activation remains unknown. In this study, we found that the upregulation of CBX7 during hypoxia and ischaemia appeared to be from hypoxia-inducible factor-1α (HIF-1α) activation. During hypoxia, the HIF-1α-CBX7 cascade modulated NPC proliferation in vitro. NPC numbers significantly decreased in CBX7 knockout mice generated using CRISPR/Cas9 genome editing. CONCLUSIONS: We provided the novel insight that CBX7 expression is regulated through HIF-1α activation, which plays an intrinsically modulating role in NPC proliferation.

Insulin enhances and metformin reduces risk of colorectal carcinoma in type-2 diabetes.

BACKGROUND: Identifying colorectal cancer associated risks is important for conducting a program for the survey and prevention of colorectal cancer. AIM: To investigate the association between use of insulin or metformin with colorectal cancer (CRC) in type 2 diabetes (T2DM). DESIGN: Population-based cohort study. METHODS: Through analysis of National Health Insurance (NHI) database between 1998 and 2010 in Taiwan, we identified 66 324 T2DM patients aged ≥ 20 years and selected subjects without diabetes by 1: 1 randomly matching with the study cohort based on age, sex and index date. We followed up the participants until 31 December 2011 or when they withdrew from the NHI program. RESULTS: Compared with non-diabetic subjects, the T2DM patients exhibited an increased risk of CRC [adjusted HR (aHR) = 1.56, 95% confidence interval (CI) = 1.39-1.75], after adjustment for age, sex, urbanization level, comorbidities and examinations of colonoscopy, sigmoidoscopy, or stool occult blood test. Among the T2DM patients, insulin usage increased the risk of CRC (aHR = 1.86, 95% CI = 1.58-0-2.19) after adjustment for age, sex, urbanization level, comorbidities, metformin usage and examinations; nevertheless, metformin decreased the risk of CRC (aHR = 0.65, 95% CI = 0.54-0.77) after adjustment for age, sex, urbanization level, comorbidities, insulin usage and examinations. Compared with the non-insulin cohort, the risk of CRC tended to increase with the incremental dosage of insulin exposure. CONCLUSION: Our population-based cohort study demonstrated an association between T2DM and CRC. Among the T2DM patients, insulin use was associated with an increased risk of CRC and metformin use was associated with a decreased risk of CRC. Inability to obtain information on several potential confounding factors, such as lifestyle and dietary habits, is the major limitation of the study.

Antiplatelet agents for the secondary prevention of ischaemic stroke in patients with or without renal dysfunction.

BACKGROUND AND PURPOSE: Studies on using antiplatelet agents for secondary prevention in ischaemic stroke patients with renal dysfunction are limited. The Taiwan Stroke Registry database was used to compare the efficacy of antiplatelet agents. METHODS: From the Taiwan Stroke Registry data, 39 174 acute ischaemic stroke patients were identified and were classified into three groups by antiplatelet agent: aspirin, clopidogrel and dual antiplatelet therapy (DAPT) with a combination of aspirin and clopidogrel. The re-stroke incidence and 1-year mortality were stratified by estimated glomerular filtration rate (eGFR) levels at admission: ≥90, 60-89 and <60 ml/min/1.73 m2 or on dialysis. RESULTS: Compared to the aspirin group, the re-stroke differences were not statistically significant for the clopidogrel group [adjusted subhazard ratio 0.95, 95% confidence interval (CI) 0.84-1.08] and the DAPT group (adjusted subhazard ratio 1.03, 95% CI 0.77-1.39) after controlling for the competing risk of death. The mortality rate increased as the eGFR level declined. In addition, compared to patients taking aspirin, there was no statistically significant difference in overall 1-year mortality for the clopidogrel group (adjusted hazard ratio 1.11, 95% CI 0.95-1.29) and for the DAPT group (adjusted hazard ratio 1.01, 95% CI 0.67-1.54). The results were consistent in different subgroups stratified by eGFR levels. CONCLUSIONS: There was no difference in the risks of recurrent stroke and 1-year mortality amongst ischaemic stroke patients with or without renal dysfunction receiving antiplatelet agents with aspirin, clopidogrel or dual agents with a combination of aspirin and clopidogrel, regardless of their renal dysfunction status.

Combination immunosuppressant therapy and lupus nephritis outcome: a hospital-based study.

Lupus nephritis (LN) is the leading cause of mortality in lupus patients. This study aimed to investigate the treatment outcome and renal histological risk factors of LN in a tertiary referral center. Between 2006 and 2017, a retrospective observational study enrolled 148 biopsy-proven LN patients. After propensity score matching, 75 cases were included for further analysis. The classification and scoring of LN were assessed according to the International Society of Nephrology/Renal Pathology Society. Treatment response was evaluated by daily urine protein and urinalysis at two years after commencing induction treatment and the development of end-stage renal disease (ESRD). In total, 50.7% patients achieved complete remission (CR) or partial remission (PR), while 49.3% patients were categorized as nonresponders. Therapeutic responses in terms of CR/PR rates were associated with Systemic Lupus Erythematosus Disease Activity Index scores (odds ratio (OR): 1.34, 95% confidence interval (CI): 1.12-1.60, p = 0.001). Moreover, higher baseline creatinine levels (hazard ratio (HR): 2.10, 95% CI: 1.29-3.40, p = 0.003), higher renal activity index (HR: 1.30, 95% CI: 1.07-1.58, p = 0.008) and chronicity index (HR: 1.40, 95% CI: 1.06-1.85, p = 0.017) predicted ESRD. Among pathological scores, cellular crescents (HR: 4.42, 95% CI: 1.01-19.38, p = 0.049) and fibrous crescents (HR: 5.93, 95% CI: 1.41-24.92, p = 0.015) were independent risk factors for ESRD. In conclusion, higher lupus activity was a good prognostic marker for renal remission. Renal histology was predictive of ESRD. Large-scale prospective studies are required to verify the efficacy of mycophenolate in combination with azathioprine or cyclosporine in LN patients.

Clinical outcomes associated with anti-coagulant therapy in patients with renal infarction.

Background: Patients with renal infarction are vulnerable to thromboembolic complications with poor outcomes. There is limited report concerning the effect of anti-coagulant therapy in this population. Aim: To assess the impact of anti-coagulant therapy on outcomes in patients with renal infarction. Design: A retrospective cohort study of 101 renal infarction patients was conducted. Methods: The association between anti-coagulant therapy, all-cause mortality, thromboembolic complications and renal outcome was evaluated. Demographic data and comorbidities were collected for analysis. Anti-coagulant therapy was treated as a time-dependent variable. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using multi-variate Cox proportional hazards models. Results: Fifty-seven (56.4%) patients with renal infarction received anti-coagulant therapy during the study period. The all-cause mortality rate was 7.56 per 100 patient-years. Age (HR 1.05, 95% CI 1.02-1.08) was a risk factor for all-cause mortality and anti-coagulant therapy was associated with a 92% improved survival (HR 0.08, 95% CI 0.02-0.34). Twelve (11.9%) thromboembolic events occurred following renal infarction. Current smoking (HR 10.37, 95% CI 1.60-67.43) had an adverse effect and anti-coagulant therapy (HR 0.14, 95% CI 0.03-0.73) had a significant protective impact on thromboembolic complications. There was no significant association between anti-coagulant therapy and long-term renal outcome in renal infarction patients including the monthly change in the estimated glomerular filtration rate (eGFR), the incidence of eGFR reduction of more than 50% and end-stage renal disease. Conclusion: Anti-coagulant therapy in patients with renal infarction was associated with better survival and reduced thromboembolic complications.

Risk of hypertension after hysterectomy: a population-based study.

OBJECTIVE: Hysterectomy is the second most common surgery performed mainly for benign uterine pathologies in females. The association between hysterectomy and the subsequent risk of hypertension remains controversial. This study investigated the risk of developing hypertension in women who had a hysterectomy. DESIGN: Population-based retrospective cohort study. SETTING: We used the Taiwan National Health Insurance Research Database with claims data of 1 million randomly selected insured individuals. POPULATION: Women with and without hysterectomy and bilateral salpingo-oophorectomy, aged 30-49 years, were identified in 2000-2013 from the insurance data. METHODS: From the claims data, we identified 6674 women with hysterectomy without hypertension at the time of the surgery. The comparison cohort were 26 696 women randomly selected from women without hysterectomy and hypertension, matched by age and the year hysterectomy was performed. Adjusted hazard ratio (aHR) of hypertension was estimated after controlling for comorbidities. MAIN OUTCOME MEASURE: Prediction for hypertension following hysterectomy for benign disease. RESULTS: Both cohorts had a median age of 43.9 years. After a median follow up of 6.4 years, the incident hypertension was higher in the hysterectomy cohort than in the comparison cohort, with an adjusted hazard ratio (aHR) of 1.35 [95% confidence interval (CI) 1.27-1.44]. The incidence increased with age, with a higher aHR in hysterectomised women aged 40-49 years (aHR 1.37, 95% CI 1.06-1.83) than in those aged 30-39 years (aHR 1.22, 95% CI 1.02-1.46). CONCLUSION: Findings in this study suggest that women with hysterectomy are more likely to be diagnosed with hypertension in the follow-up period. TWEETABLE ABSTRACT: Women with hysterectomy before 50 years of age are at an increased risk of developing subsequent hypertension. PLAIN LANGUAGE SUMMARY: Hysterectomy is one of the most common surgeries for women with benign uterine disease. Hysterectomy may lead to a sudden decline in the production of sex hormone (estrogen and progesterone), which is responsible for vessel wall endothelial dysfunction leading to hardening of arteries and subsequent hypertension. However, the association between hysterectomy and risk of hypertension remains controversial. This study investigated whether premenopausal women have an elevated risk of hypertension after hysterectomy. This study employed the Taiwan National Health Insurance Research Database to identify 6674 women 30-49 years old who had a hysterectomy between 2000 and 2013, and a comparison group of 26 696 women who did not have a hysterectomy matched by age. Women in both the groups had no hypertension at baseline (recruiting date or within 1 year after recruiting date). By the end of 2013, we found that 1196 (17.9%) and 3613 (13.5%) women had developed hypertension in the hysterectomy and the comparison groups, respectively. The hypertension incidence was 1.4-fold greater in the hysterectomy group than in the control group (27.8 versus 20.2/1000 person-years).

Rehydration before wet fixation in conventional body fluid cytology - An 18-year experience.

PURPOSE: In conventional cytology, preparation of a specimen by wet fixation for Papanicolaou stain is potentially subject to dry effect or cell loss which may make cytologic interpretation difficult or even impossible. We have been routinely making an additional smear for rehydration with normal saline (rehydration method) before wet fixation to overcome the above shortcomings. METHODS: We reviewed malignant pleural effusion and ascites 15 cases each in our cytology laboratory over the past 1 year. Four slides of each specimen were made. Two were air-dried for Liu's stain (a Romanowsky stain) and the other two were wet-fixed for Papanicolaou stain. The air-dried smears were also served as retained cellularity control. One of the two wet-fixed smears was processed as a control of preservation of nuclear detail whereas the other one stayed air-dried for 10 minutes and then covered with normal saline (rehydration method) for 80 seconds before wet fixation. RESULTS: There was minor cell loss (P = .032). The cells appeared larger with good preservation of nuclear detail (P < .0001 by two-sided Wilcoxon rank sum test) but no red blood cells retained on the slide after rehydration. CONCLUSION: The rehydration method can effectively minimise cell loss, enlarge and preserve the cytological features of malignant cells with haemolysis. This method is simple, practical and good for cytological screening for tumour cells and interpretation especially in a bloody smear. We recommend that the rehydration method be part of traditional cytopreparatory work of wet fixation for Papanicolaou stain in conventional body fluid cytology.

Cancer-related hypercalcemia in oral cancer.

Cancer-related hypercalcemia (CRH) is a critical paraneoplastic disorder in advanced cancer patients. In clinical practice, patients with CRH have a poor prognosis. The medical records of 3198 oral cancer patients with CRH diagnosed at Taichung Veterans General Hospital from 1 January 2003 to 31 December 2015 were reviewed. The criteria for patient enrolment were a diagnosis of hypercalcemia or the use of antihypercalcemia medication. Patients who met any of the following criteria were excluded: use of total parenteral nutrition, incomplete serum calcium data, and unknown date of death. The total incidence of CRH was 6.95‰ per year. A total of 91 patients were enrolled; their median survival time was 28 days. The patients were divided into two groups by survival time, with a cut-off point of 30 days. Reduced serum albumin, leucocytosis, and clodronate use had a statistically significant effect on survival in the univariate analysis (all P<0.05). Forty-five patients (49.5%) had recurrence of CRH, of whom nine died within 30days. These nine patients had a shorter interval to the first episode of CRH recurrence (median 13 days) than those who survived ≥30days (median 28 days) (P<0.001). It was observed that a short interval to the first episode of CRH recurrence is a poor prognostic factor.

Urinary Markers of Fibrosis and Risk of Cardiovascular Events and Death in Kidney Transplant Recipients: The FAVORIT Trial.

Cardiovascular risk remains high in kidney transplant recipients (KTRs) despite improved kidney function after transplant. Urinary markers of kidney fibrosis and injury may help to reveal mechanisms of this risk. In a case-cohort study among stable KTRs who participated in the FAVORIT trial, we measured four urinary proteins known to correlate with kidney tubulointerstitial fibrosis on biopsy (urine alpha 1 microglobulin [α1m], monocyte chemoattractant protein-1 [MCP-1], procollagen type I [PINP] and type III [PIIINP] N-terminal amino peptide) and evaluated associations with cardiovascular disease (CVD) events (n = 300) and death (n = 371). In adjusted models, higher urine α1m (hazard ratio [HR] per doubling of biomarker 1.40 [95% confidence interval [CI] 1.21, 1.62]), MCP-1 (HR 1.18 [1.03, 1.36]), and PINP (HR 1.13 [95% CI 1.03, 1.23]) were associated with CVD events. These three markers were also associated with death (HR per doubling α1m 1.51 [95% CI 1.32, 1.72]; MCP-1 1.31 [95% CI 1.13, 1.51]; PINP 1.11 [95% CI 1.03, 1.20]). Higher concentrations of urine α1m, MCP-1, and PINP may identify KTRs at higher risk for CVD events and death. These markers may identify a systemic process of fibrosis involving both the kidney and cardiovascular system, and give new insights into mechanisms linking the kidney with CVD.

Association between radical prostatectomy and risk of herpes zoster.

The present study investigated the association between radical prostatectomy (RP) and the risk of herpes zoster (HZ). Male patients aged ≥ 40 years and diagnosed with prostate cancer (PCa) between 2000 and 2005 were included in this study. Patients who underwent RP for the first time during 2000-2006 were included in the RP group. Randomly selected individuals from among the remaining patients with PCa who did not undergo RP were included in the non-RP group. Univariate and multivariate Cox regression models were used to analyze the association between PCa and HZ. In addition, the association between RP and the risk of HZ in different subgroups was evaluated after stratification by age, comorbidities, and hormone therapy (HoT) status. Furthermore, the combined effect of RP and HoT on the risk of HZ was evaluated. This study included 1,380 patients with PCa who newly underwent RP and 1,371 patients with PCa who did not undergo RP. During follow-up, 96 and 104 patients in the RP and non-RP groups, respectively, developed HZ. Patients who underwent both RP and HoT showed a significantly reduced risk of HZ, compared with patients who did not undergo both RP and HoT. RP is not associated with an increased risk of HZ. However, prostate-specific antigen levels should be monitored routinely during follow-up to detect PCa recurrence.

Impact of mTOR Inhibitors on Cancer Development in Kidney Transplantation Recipients: A Population-Based Study.

BACKGROUND: The mammalian target of rapamycin (mTOR) inhibitor is an immunosuppressive drug used in kidney transplantation. Whether the mTOR inhibitor is associated with reduced risk of cancer development and mortality after kidney transplantation is controversial. METHODS: We conducted a nationwide population-based study. Patients who did not have malignancy history and received kidney transplantation between 2010 and 2013 were enrolled. Recipients who had mTOR inhibitors (n = 430) for more than 30 days comprised the study group; 1720 recipients who did not have mTOR inhibitors comprised the control group. The primary outcome is the development of cancer after kidney transplantation. These patients were followed until the first-time admission with diagnosis of cancer, death, or the end of 2014. A Cox proportional-hazard model was used to determine the risk of cancer development and all-cause mortality. RESULTS: During the 35-month median duration of observation, there were 16 and 61 patients with cancer development in the study group and the control group, respectively. The cancer incidence was 12.8 and 12.4 per 1000 person-years. There were 10 and 135 mortality cases, with the incidence rate of 7.8 and 26.9 per 1000 person-years. After multivariable adjustment, the mTOR inhibitors users were not associated with reduced risk of new cancer development as compared with control (hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.46-1.60; P = .63), nor risk of all-cause mortality (HR, 0.70; 95% CI, 0.33-1.46; P = .34). CONCLUSIONS: The use of mTOR inhibitors was not associated with a reduction in the risk of cancer development and all-cause mortality in kidney transplantation recipients.

Herb formula enhances treatment of impotent patients after penile venous stripping: a randomised clinical trials.

Herbs have been regarded as aphrodisiacs in treating impotence for many centuries despite little true scientific evidence. Our latest refined penile venous stripping (PVS) technique is effective in treating impotence, although this procedure remains controversial. A synergic effect of PVS and oral herbs was confirmed in our practice but lacked rigorous scientific proof. The objective of this report was to review our experience with this combination. From August 2010 to May 2014, 263 males underwent PVS. Among these, 67 unsatisfied men chose additional salvage therapy and were randomly assigned to oral herbs (n = 35) or placebo treatment (n = 32) which replaced herb eventually. All were evaluated with the international index of erectile function (IIEF-5) scoring and our dual pharmaco-cavernosography. The pre-op IIEF-5 score for the herb group was 9.7 ± 3.7, post-operative 13.9 ± 3.3 and post-herb 19.6 ± 3.4, while the control group scores were as follows: pre-op 9.3 ± 4.1, post-op 14.5 ± 3.6, post-placebo 15.1 ± 3.5 and post-herb 19.9 ± 3.2. Although there was no significant difference between the two groups pre-operatively, post-operatively and post-herb, a statistically significant difference was found post-salvage therapy (19.6 ± 3.4 versus 15.1 ± 3.6, P < 0.001). It appears that the combination of oral herbs and PVS treatment provides an enhanced outcome to impotent patients refractory to medicine and unsatisfied with PVS monotherapy alone.