Prevalence of Kidney and Urinary Tract Complications in Fabry Disease from 2000 to 2020: A Global Cohort Study Including 10,637 Patients.

BACKGROUND/AIM: Fabry disease, an X-linked lysosomal storage disorder, causes progressive globotriaosylceramide accumulation in cells throughout the body. Characteristic multiorgan manifestations include renal dysfunction (Fabry nephropathy) and associated urinary tract complications. Enzyme replacement therapy (ERT) has been available since 2001, but contemporary real-world data are lacking regarding Fabry nephropathy risks and treatment outcomes. PATIENTS AND METHODS: This retrospective cohort study analyzed electronic medical records data for 10,637 Fabry disease patients from the TriNetX research database. Kidney and urinary tract outcomes were evaluated over two decades, 2000-2010 and 2011-2020. Outcomes assessed included chronic kidney disease (CKD), urinary tract infections, urinary incontinence, obstruction, renal insufficiency, and end-stage renal disease (ESRD). RESULTS: The prevalence of stage 4-5 CKD nearly doubled between 2000-2010 and 2011-2020, while ESRD prevalence rose over 4-fold. Incidence rates showed similar marked elevations across renal and urologic complications. Females and Black patients experienced disproportionate escalations in kidney and urinary tract morbidity. CONCLUSION: This large cohort study revealed significantly increased Fabry nephropathy and associated urologic complications over the past two decades, contradicting expectations of reduced morbidity with ERT availability. The findings highlight needs to optimize screening, treatment strategies, monitoring practices, and address disparities to curb rising disease burden and improve patient outcomes.

Development of anti-aflatoxin B1 nanobodies from a novel mutagenesis-derived synthetic library for traditional Chinese medicine and foods safety testing.

BACKGROUND: The main commercially available methods for detecting small molecules of mycotoxins in traditional Chinese medicine (TCM) and functional foods are enzyme-linked immunosorbent assay and mass spectrometry. Regarding the development of diagnostic antibody reagents, effective methods for the rapid preparation of specific monoclonal antibodies are inadequate. METHODS: In this study, a novel synthetic phage-displayed nanobody Golden Glove (SynaGG) library with a glove-like cavity configuration was established using phage display technology in synthetic biology. We applied this unique SynaGG library on the small molecule aflatoxin B1 (AFB1), which has strong hepatotoxicity, to isolate specific nanobodies with high affinity for AFB1. RESULT: These nanobodies exhibit no cross-reactivity with the hapten methotrexate, which is recognized by the original antibody template. By binding to AFB1, two nanobodies can neutralize AFB1-induced hepatocyte growth inhibition. Using molecular docking, we found that the unique non-hypervariable complementarity-determining region 4 (CDR4) loop region of the nanobody was involved in the interaction with AFB1. Specifically, the CDR4's positively charged amino acid arginine directed the binding interaction between the nanobody and AFB1. We then rationally optimized the interaction between AFB1 and the nanobody by mutating serine at position 2 into valine. The binding affinity of the nanobody to AFB1 was effectively improved, and this result supported the use of molecular structure simulation for antibody optimization. CONCLUSION: In summary, this study revealed that the novel SynaGG library, which was constructed through computer-aided design, can be used to isolate nanobodies that specifically bind to small molecules. The results of this study could facilitate the development of nanobody materials to detect small molecules for the rapid screening of TCM materials and foods in the future.

Ethnic differences in the age-related distribution of serum prostate-specific antigen values: A study in a Taiwanese male population.

This study investigates age-specific prostate-specific antigen (PSA) distributions in Taiwanese men and recommends reference ranges for this population after comparison with other studies. From January 1999 to December 2016, a total of 213,986 Taiwanese men aged above 19 years old without history of prostate cancer, urinary tract infection, or prostate infection were recruited from the Taiwan MJ cohort, an ongoing prospective cohort of health examinations conducted by the MJ Health Screening Center in Taiwan. Participants were divided into seven age groups. Simple descriptive statistical analyses were carried out and quartiles and 95th percentiles were calculated for each group as reference ranges for serum PSA in screening for prostate cancer in Taiwanese men. Serum PSA concentration correlated with age (r = 0.274, p<0.001). The median serum PSA concentration (5th to 95th percentile) ranged from 0.7 ng/ml (0.3 to 1.8) for men 20-29 years old (n = 6,382) to 1.6 ng/ml (0.4 to 8.4) for men over 79 years old (n = 504). The age-specific PSA reference ranges are as follows: 20-29 years, 1.80 ng/ml; 30-39 years, 1.80 ng/ml; 40-49 years, 2.0 ng/ml; 50-59 years, 3.20 ng/ml; 60-69 years, 5.60 ng/ml; 70-79 years, 7.40 ng/ml; over 80 years, 8.40 ng/ml. Almost no change occurred in the median serum PSA value in men 50 years old or younger, while a gradual increase was observed in men over 50. Taiwanese men aged 60 years above showed higher 95th percentile serum PSA values compared to Caucasian men and men in other Asian countries but were closer to those of Asian American and African American men. Results indicate significantly different PSA levels correlating to different ethnicities, suggesting that Oesterling's age-specific PSA reference ranges might not be appropriate for Taiwanese men. Our results should be further studied to validate the age-specific PSA reference ranges for Taiwanese men presented in this study.

Comparison of the risks of renal cell carcinoma or urothelial cancer between hemodialysis and peritoneal dialysis patients.

PURPOSE: This study is to compare risks of developing renal cell carcinoma or urothelial cancer between hemodialysis (HD) and peritoneal dialysis (PD) patients. METHODS: The age-, sex-, and index year-matched patients with newly diagnosed end-stage kidney disease (ESKD) undergoing dialysis [HD (N = 22,587) or PD (N = 11,547)] from 2000 to 2015 in Taiwan were identified. Patients were followed until the development of renal cell carcinoma or urothelial cancer, renal transplantation, death, or the end of follow-up (December 31, 2017). The hazard ratio (HR), and sub-hazards ratio (SHR), in which death was considered as a competing risk, of developing renal cell carcinoma or urothelial cancer were compared between the HD and PD patients. RESULTS: The incidence rate of renal cell carcinoma was higher in the PD group than in age-, sex-, and index year-matched HD group (11.5 versus 5.52 per 10,000 person-years), with an adjusted HR of 2.15 (95% confidence interval (CI) = 1.59, 2.92), and an adjusted SHR of 1.97 (95% CI = 1.46, 2.67). The incidence rate of urothelial cancer was also higher in the PD group than in corresponding HD group (40.3 and 34.0 per 10,000 person-years), with an adjusted HR of 1.15 (95% CI = 1.00, 1.33) and an adjusted SHR of 1.08 (95% CI = 0.94, 1.25). These findings were further validated in propensity score-matched dialysis cohorts. CONCLUSIONS: ESKD patients undergoing PD are at a higher risk of developing renal cell carcinoma than those on HD, but risks of developing urothelial cancer are similar among the two groups.

T Cells Mediate Kidney Tubular Injury via Impaired PDHA1 and Autophagy in Type 1 Diabetes.

CONTEXT: Nephropathy is a severe complication of type 1 diabetes (T1DM). However, the interaction between the PDHA1-regulated mechanism and CD4+ T cells in the early stage of kidney tubular injury remains unknown. OBJECTIVE: To evaluate the role of PDHA1 in the regulation of tubular cells and CD4+ T cells and further to study its interaction in tubular cell injury in T1DM. METHODS: Plasma and total RNA were collected from T cells of T1DM patients (n = 35) and healthy donors (n = 33) and evaluated for neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1, PDHA1, and biomarkers of CD4+ T cells including T helper 1 cells (Th1) and regulatory T cells (Treg) markers. HK-2 cells cocultured with CD4+ T cells from T1DM patients or healthy donors (HDs) to evaluate the interaction with CD4+ T cells. RESULTS: Increased PDHA1 gene expression levels in CD4+ T cells were positively associated with the plasma level of NGAL in T1DM patients and HDs. Our data demonstrated that the Th1/Treg subsets skewed Th1 in T1DM. Knockdown of PDHA1 in kidney tubular cells decreased ATP/ROS production, NAD/NADH ratio, mitochondrial respiration, and cell apoptosis. Furthermore, PDHA1 depletion induced impaired autophagic flux. Coculture of tubular cells and T1DM T cells showed impaired CPT1A, upregulated FASN, and induced kidney injury. CONCLUSION: Our findings indicate that Th1 cells induced tubular cell injury through dysregulated metabolic reprogramming and autophagy, thereby indicating a new therapeutic approach for kidney tubular injury in T1DM.

A Concordance Study of COMLEX-USA and USMLE Scores.

BACKGROUND: Under the single GME accreditation system, residency programs receive applicants from MD- and DO-granting medical schools, each of which have their own set of licensing examinations, making concordance studies increasingly relevant. Previous studies comparing Comprehensive Osteopathic Medical Licensing Examination of the United States (COMLEX-USA) and United States Medical Licensing Examination (USMLE) scores have been limited in sample size and examinee composition and have yielded comparisons that may not be generalizable across all applicants. Some osteopathic medical students take USMLE in addition to COMLEX-USA, often at considerable cost and effort, with the aim of making themselves more desirable to potential residency programs. Having more reliable comparisons of COMLEX-USA and USMLE scores would allow program directors to better estimate a score on the alternate examination. OBJECTIVE: To derive an accurate concordance between COMLEX-USA and USMLE scores, based on a large sample of osteopathic students who took both examinations. METHODS: Five colleges of osteopathic medicine, representing various regions of the United States, participated in this study. The data included demographics and COMLEX-USA and USMLE scores from September 2015 through August 2020 for students who took both examinations. We derived the concordance between COMLEX-USA and USMLE scores using equipercentile matching. RESULTS: Comparisons of demographic characteristics showed only minor differences between the sample and the overall population for COMLEX-USA takers, although scores for the study sample were, on average, greater. CONCLUSIONS: A strong association exists between the scores on the COMLEX-USA and USMLE examinations, allowing prediction of performance on USMLE from COMLEX-USA.

Examining concurrent validity between COMLEX-USA Level 2-Cognitive Evaluation and COMLEX-USA Level 2-Performance Evaluation.

CONTEXT: The Comprehensive Osteopathic Medical Licensing Examination of the United States of America (COMLEX-USA) is a three level examination used as a pathway to licensure for students in osteopathic medical education programs. COMLEX-USA Level 2 includes a written assessment of Fundamental Clinical Sciences for Osteopathic Medical Practice (Level 2-Cognitive Evaluation [L2-CE]) delivered in a computer based format and separate performance evaluation (Level 2-Performance Evaluation [L2-PE]) administered through live encounters with standardized patients. L2-PE was designed to augment L2-CE. It is expected that the two examinations measure related yet distinct constructs. OBJECTIVES: To explore the concurrent validity of L2-CE with L2-PE. METHODS: First attempt test scores were obtained from the National Board of Osteopathic Medical Examiners database for 6,639 candidates who took L2-CE between June 2019 and May 2020 and matched to the students' L2-PE scores. The sample represented all colleges of osteopathic medicine and 97.5% of candidates who took L2-CE during the complete 2019-2020 test cycle. We calculated disattenuated correlations between the total score for L2-CE, the L2-CE scores for the seven competency domains (CD1 through CD7), and the L2-PE scores for the Humanistic Domain (HM) and Biomedical/Biomechanical Domain (BM). All scores were on continuous scales. RESULTS: Pearson correlations ranged from 0.10 to 0.88 and were all statically significant (p<0.01). L2-CE total score was most strongly correlated with CD2 (0.88) and CD3 (0.85). Pearson correlations between the L2-CE competency domain subscores ranged from 0.17 to 0.70, and correlations which included either HM or BM ranged from 0.10 to 0.34 with the strongest of those correlations being between BM and L2-CE total score (0.34) as well as between HM and BM (0.28).The largest increase between corresponding Pearson and disattenuated correlations was for pairs of scores with lower reliabilities such as CD5 and CD6, which had a Pearson correlation of 0.17 and a disattenuated correlation of 0.68. The smallest increase in correlations was observed in pairs of scores with larger reliabilities such as L2-CE total score and HM, which had a Pearson correlation of 0.23 and a disattenuated correlation of 0.28. The reliability of L2-CE was 0.87, 0.81 for HM, and 0.73 for BM. The reliabilities for the L2-CE competency domain scores ranged from 0.22 to 0.74. The small to moderate correlations between the L2-CE total score and the two L2-PE support the expectation that these examinations measure related but distinct constructs. The correlations between L2-PE and L2-CE competency domain subscores reflect the distribution of items defined by the L2-PE blueprint, providing evidence that the examinations are performing as designed. CONCLUSIONS: This study provides evidence supporting the validity of the blueprints for constructing COMLEX-USA Levels 2-CE and 2-PE examinations in concert with the purpose and nature of the examinations.

Meaningful use of COMSAE Phase 1 in preparation for COMLEX-USA Level 1.

CONTEXT: The Comprehensive Osteopathic Medical Licensing Examination of the United States (COMLEX-USA) is a three level national standardized licensure examination for the practice of osteopathic medicine. The Comprehensive Medical Self Assessment Examination (COMSAE) is a three phase self assessment tool designed to gauge the base knowledge and ability of candidates preparing for COMLEX-USA. OBJECTIVES: To investigate how COMSAE Phase 1 (Phase 1) was used by candidates and how completing Phase 1 impacted their performance on the COMLEX-USA Level 1 (Level 1) examination. METHODS: Using data from the 2018-2019 administration of Level 1 and Phase 1 examinations, we counted the frequency of the unique Phase 1 forms taken by the candidates and calculated the correlation between the candidates' first attempt Phase 1 scores and the number of Phase 1 forms taken. We then calculated the correlation between the Level 1 scores and the Phase 1 scores. Next, we applied a multilevel regression model to examine the candidates' score improvement on the multiple Phase 1 forms taken. Finally, we investigated the effect of practicing through Phase 1 on the candidates' Level 1 performance using logistic regression models. RESULTS: The majority of candidates took one (2,414; 33.9%) to two (2,196; 30.8%) timed Phase 1 forms prior to the Level 1 examination. There was a significant negative correlation (r=-0.48, t(6,505)=-44.05, p<0.001) between the candidates' first attempt Phase 1 scores and the number of Phase 1 forms taken. There was a strong and positive correlation (r=0.66 to 0.74, p<0.001) between Phase 1 and Level 1 scores. With other variables controlled, on average, candidates' Phase 1 scores increased 23.2 points on one attempt from the previous attempt. Having the most recent Phase 1 score controlled, a greater number of Phase 1 forms taken was associated with an improvement on the Level 1 performance. CONCLUSIONS: The significant correlation between Phase 1 and Level 1 performance provided validity evidence for Phase 1. Moreover, our results suggested that candidates, especially those with lower performance on their initial Phase 1 attempt, might improve their Level 1 performance by taking multiple Phase 1 forms to monitor their academic improvement and gauge their readiness for Level 1.

Generation of avian-derived anti-B7-H4 antibodies exerts a blockade effect on the immunosuppressive response.

For highly conserved mammalian protein, chicken is a suitable immune host to generate antibodies. Monoclonal antibodies have been successfully targeted with immunity checkpoint proteins as a means of cancer treatment; this treatment enhances tumor-specific immunity responses through immunoregulation. Studies have identified the importance of B7-H4 in immunoregulation and its use as a potential target for cancer treatment. High levels of B7-H4 expression are found in tumor tissues and are associated with adverse clinical and pathological characteristics. Using the phage display technique, this study isolated specific single-chain antibody fragments (scFvs) against B7-H4 from chickens. Our experiment proved that B7-H4 clearly induced the inhibition of T-cell activation. Therefore, use of anti-B7-H4 scFvs can effectively block the exhaustion of immunity cells and also stimulate and activate T-cells in peripheral blood mononuclear cells. Sequence analysis revealed that two isolated scFv S2 and S4 have the same VH complementarity-determining regions (CDRs) sequence. Molecule docking was employed to simulate the complex structures of scFv with B7-H4 to analyze the interaction. Our findings revealed that both scFvs employed CDR-H1 and CDR-H3 as main driving forces and had strong binding effects with the B7-H4. The affinity of scFv S2 was better because the CDR-L2 loop of the scFv S2 had three more hydrogen bond interactions with B7-H4. The results of this experiment suggest the usefulness of B7-H4 as a target for immunity checkpoints; the isolated B7-H4-specific chicken antibodies have the potential for use in future cancer immunotherapy applications.

CATALYST: Piloting a Longitudinal Assessment and Learning Program for Board Recertification and Continuous Professional Development.

Context: As a proposed alternative to the traditional recertification examination, CATALYST is a longitudinal formative assessment platform created on cognitive learning principles. CATALYST was designed by the National Board of Osteopathic Medical Examiners to encourage more complex and durable practice-relevant learning and demonstration of ongoing competencies. Objective: To investigate the value of the CATALYST platform using board diplomates' subjective feedback and comparison of performance on CATALYST questions with performance on board examinations. Methods: Diplomates from 3 osteopathic specialty boards (the American Osteopathic Board of Internal Medicine, the American Osteopathic Board of Pediatrics, and the American Osteopathic Board of Obstetricians and Gynecologists) participated in this pilot study. Over the course of 16 weeks, participants were provided 2 questions per week via the CATALYST platform. An evaluation survey was emailed at the end of the study period to collect participants' feedback. Survey results and correlations of CATALYST performance with past or upcoming board examination scores were analyzed. Results: A total of 196 diplomates completed the surveys, with 95% reporting that participation in the platform would help them stay current in their specialties and 91% reporting that participation would help them provide better care to their patients. For the AOBIM, a significant correlation was found between the number of CATALYST questions answered correctly and performance on the board examination (r=0.51, P<.001). The correlations found for the AOBP and AOBOG were not significant (r=0.197, P=.296, and r=0.370, P=.075, respectively). Conclusion: The CATALYST platform could offer valuable contributions to the board recertification process and to patient safety. Further investigations are being conducted on a new user-friendly platform.

CATALYST: Piloting a Longitudinal Assessment and Learning Program for Board Recertification and Continuous Professional Development.

CONTEXT: As a proposed alternative to the traditional recertification examination, CATALYST is a longitudinal formative assessment platform created on cognitive learning principles. CATALYST was designed by the National Board of Osteopathic Medical Examiners to encourage more complex and durable practice-relevant learning and demonstration of ongoing competencies. OBJECTIVE: To investigate the value of the CATALYST platform using board diplomates' subjective feedback and comparison of performance on CATALYST questions with performance on board examinations. METHODS: Diplomates from 3 osteopathic specialty boards (the American Osteopathic Board of Internal Medicine, the American Osteopathic Board of Pediatrics, and the American Osteopathic Board of Obstetricians and Gynecologists) participated in this pilot study. Over the course of 16 weeks, participants were provided 2 questions per week via the CATALYST platform. An evaluation survey was emailed at the end of the study period to collect participants' feedback. Survey results and correlations of CATALYST performance with past or upcoming board examination scores were analyzed. RESULTS: A total of 196 diplomates completed the surveys, with 95% reporting that participation in the platform would help them stay current in their specialties and 91% reporting that participation would help them provide better care to their patients. For the AOBIM, a significant correlation was found between the number of CATALYST questions answered correctly and performance on the board examination (r=0.51, P<.001). The correlations found for the AOBP and AOBOG were not significant (r=0.197, P=.296, and r=0.370, P=.075, respectively). CONCLUSION: The CATALYST platform could offer valuable contributions to the board recertification process and to patient safety. Further investigations are being conducted on a new user-friendly platform.

A Validity Study of COMLEX-USA Level 2-CE and COMAT Clinical Subjects: Concurrent and Predictive Evidence.

BACKGROUND: The Comprehensive Osteopathic Medical Licensure Examination (COMLEX-USA) Level 2-Cognitive Examination (CE) and the Comprehensive Osteopathic Medical Achievement Test (COMAT) are administered to similar populations (third- and fourth-year osteopathic students) at similar points in time. Examining the relationship between scores on the 2 assessments that measure similar constructs ultimately supports the validity of both. OBJECTIVE: The purpose of this study is to provide empirical evidence of the concurrent and predictive validity of COMAT and COMLEX-USA Level 2-CE. METHODS: In 2018, first-attempt scores on Level 2-CE were aggregated from June 2015 to May 2018 and matched with first-attempt scores on each COMAT clinical subject. We conducted correlational analyses between performance on COMAT and Level 2-CE, and COMAT scores and Level 2-CE discipline subscores. Additionally, we used multivariate regression to analyze the predictive relationship between performance on all COMAT clinical subjects and Level 2-CE. RESULTS: The results from correlational analyses indicated statistically significant, positive associations between COMAT and Level 2-CE scores (r = 0.49-0.68, P < .0001), and statistically significant, but slightly weaker relationships between COMAT scores and Level 2-CE discipline subscores (r = 0.31-0.60, P < .0001). Furthermore, results from the multiple regression indicated that scores on COMAT explained 68% of the variance in Level 2-CE scores, and that COMAT internal medicine and emergency medicine were weighted more heavily than other specialties. CONCLUSIONS: The findings from this study can inform assessment practices by supporting the use of COMAT for osteopathic medical schools that do not administer COMAT.

Increased risk of new-onset type 2 diabetes in people with chronic kidney disease.

PURPOSE: This study investigated whether people with chronic kidney disease (CKD) are at the risk of new-onset type 2 diabetes. METHODS: A cohort comprising 16,624 people with CKD, and an age- and sex-matched control cohort of 66,496 persons without any clinical kidney disease were identified from the Taiwan National Health Insurance Database during the period of 2000-2010. Both cohorts were followed up to 2011 to evaluate the incidence and hazard ratio (HR) of developing new-onset type 2 diabetes. Diseases were identified based on diagnosis coding. RESULTS: The incidence of type 2 diabetes was 1.51-fold higher in the CKD cohort than in the control cohort (16.9 versus 11.2 per 1,000 person-years) with an adjusted hazard ratio of 1.17 (95% confidence interval, (CI)1.10-1.24). In the multivariate Cox regression model considering the competing-risk death, the adjusted subhazard ratio of type 2 diabetes was 1.30 (95% CI1.22-1.38) for the CKD cohort compared to the control cohort. CONCLUSIONS: People with CKD patients are at an increased risk of developing new-onset type 2 diabetes. Close surveillance for diabetes should be considered for these people.

Icodextrin is associated with a lower risk of atrial fibrillation in peritoneal dialysis patients.

AIM: Dialysis patients with atrial fibrillation (AF) are at 1.72-fold increased mortality risk. This study investigated whether peritoneal dialysis (PD) patients using icodextrin were at a reduced risk of AF. METHODS: From the Taiwan National Health Insurance database, we identified 4040 icodextrin users and 3517 non-users among 7557 patients newly diagnosed with end-stage renal disease undergoing PD from 2005 to 2011. The incidence of AF was compared between PD patients with and without icodextrin treatment by the end of 2011, with the hazard ratio (HR) of AF measured using Cox proportional hazards regression models. RESULTS: The incidence of AF was 50% lower in icodextrin users than in non-users (2.14 vs 4.24 per 1000 person-years) with an adjusted HR of 0.49 (95% confidence interval (CI) = 0.28-0.85). The protective effect was greater for PD patients with diabetes (adjusted HR = 0.39, 95% CI = 0.17-0.86) than those without diabetes (adjusted HR = 0.57, 95% CI = 0.28-1.18). The beneficial effect of icodextrin treatment remained after controlling for the competing risk of deaths, with an adjusted sub-HR of 0.35 (95% CI = 0.16-0.75) for those with diabetes and 0.50 (95% CI = 0.26-0.99) for those without diabetes. CONCLUSION: The use of icodextrin solution is associated with a lower risk of new-onset AF in PD patients. The protective effectiveness was greater for those with diabetes.

RNA-binding protein, human antigen R regulates hypoxia-induced autophagy by targeting ATG7/ATG16L1 expressions and autophagosome formation.

Autophagy, a prosurvival mechanism offers a protective role during acute kidney injury. We show novel findings on the functional role of RNA binding protein, HuR during hypoxia-induced autophagy in renal proximal tubular cells-2 (HK-2). HK-2 cells showed upregulated expressions of HuR and autophagy-related proteins such as autophagy related 7 (ATG7), autophagy related 16 like 1 (ATG16L1), and LC3II under hypoxia. Increased autophagosome formation was visualized as LC3 puncta in hypoxic cells. Further, short hairpin-RNA-mediated loss of HuR function in HK-2 cells significantly decreased ATG7 and ATG16L1 protein expressions. Bioinformatics prediction revealed HuR motif binding on the coding region of ATG7 and AU-rich element at 3'UTR ATG16L1 messnger RNA (mRNA). The RNA immunoprecipitation study showed that HuR was predominantly associated with ATG7 and ATG16L1 mRNAs under hypoxia. In addition, HuR enhanced autophagosome formation by regulating LC3II expressions. These results show that HuR regulates ATG7 and ATG16L1 expressions and thereby mediate autophagy in HK-2 cells. Importantly, HuR knockdown cells underwent apoptosis during hypoxia as observed through the terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Collectively, these findings show the crucial role of HuR under hypoxia by regulating autophagy and suppressing apoptosis in renal tubular cells.

Icodextrin is Associated with a Lower Risk of Stroke in Peritoneal Dialysis Patients.

BACKGROUND/AIMS: This study investigated whether peritoneal dialysis (PD) patients using icodextrin were at a reduced risk of stroke. METHODS: From Taiwan National Health Insurance data, it was found that there were 6,796 new end-stage renal disease patients undergoing dialysis between 2005 and 2011. We compared the risk of stroke between PD patients with or without icodextrin treatment. The follow-up period began from the date of PD initiation to the end of 2011. The time-dependent Cox proportional hazards regression models were used to analyze the risk of stroke. RESULTS: Among PD patients, the icodextrin users had both a lower incidence and risk of stroke than icodextrin non-users (incidence: 22.4 vs. 25.2/1,000 person-years) with an adjusted hazard ratio of 0.76 (95% CI 0.63-0.93). The results were similar in models considering death a competing risk (overall: adjusted subhazard ratio [SHR] 0.78, 95% CI 0.63-0.94). Icodextrin users also had a lower risk of ischemic stroke with or without considering death a competing risk (adjusted SHR 0.71, 95% CI 0.57-0.89 and adjusted HR 0.74, 95% CI 0.59-0.93, respectively), compared to non-users. CONCLUSION: The use of icodextrin is associated with a lower incidence and risk of stroke in PD patients.

Radiation-Induced Uterine Carcinosarcoma after Concurrent Chemoradiotherapy for Cervical Squamous Cell Carcinoma

Abstract Objective To describe a case of radiation-induced uterine carcinosarcoma 6 years after a cervical squamous cell carcinoma treatment, which imposed some diagnostic and management challenges. Case Report A 57-year-old woman with a history of pelvic chemoradiotherapy ~ 6.5 years before the event described in this study, following an International Federation of Gynecology and Obstetrics (FIGO) stage IIB cervical cancer, presented with a cervical mass, involving the uterine cavity, the cervical canal and the upper two thirds of the vagina. The biopsy showed a poorly differentiated carcinoma, and a positron emission tomography (PET) scan excluded distant metastasis, although it was unable to define the origin of the tumor as either a new primary malignancy of the endometrium/cervix or as a cervical recurrence. Surgical staging procedure was performed, and the diagnosis was endometrial carcinosarcoma, FIGO stage IIB. The patient was not able to complete the adjuvant therapy, and the progression of the disease was remarkable. Conclusion The present case highlights one of the less common but more serious consequences of radiotherapy for cervical cancer, which has an increasing incidence in younger women, raising concerns about the long-termconsequences of its management.

Radiation-Induced Uterine Carcinosarcoma after Concurrent Chemoradiotherapy for Cervical Squamous Cell Carcinoma.

OBJECTIVE: To describe a case of radiation-induced uterine carcinosarcoma 6 years after a cervical squamous cell carcinoma treatment, which imposed some diagnostic and management challenges. CASE REPORT: A 57-year-old woman with a history of pelvic chemoradiotherapy ∼ 6.5 years before the event described in this study, following an International Federation of Gynecology and Obstetrics (FIGO) stage IIB cervical cancer, presented with a cervical mass, involving the uterine cavity, the cervical canal and the upper two thirds of the vagina. The biopsy showed a poorly differentiated carcinoma, and a positron emission tomography (PET) scan excluded distant metastasis, although it was unable to define the origin of the tumor as either a new primary malignancy of the endometrium/cervix or as a cervical recurrence. Surgical staging procedure was performed, and the diagnosis was endometrial carcinosarcoma, FIGO stage IIB. The patient was not able to complete the adjuvant therapy, and the progression of the disease was remarkable. CONCLUSION: The present case highlights one of the less common but more serious consequences of radiotherapy for cervical cancer, which has an increasing incidence in younger women, raising concerns about the long-term consequences of its management.