Background: Kidney damage is common in patients with Fabry disease (FD), but more accurate information about the risk of progression to kidney failure is needed for clinical decision -making. In particular, FD patients with mild renal involvement often lack timely intervention and treatment. We aimed to utilize a model to predict the risk of renal progression in FD patients. Methods: Between November 2011 and November 2019, ERT-naive patients with FD were recruited from three medical centers in China. To assess the risk of a 50% decline in the estimated glomerular filtration rate (eGFR) or end -stage kidney disease (ESKD), Cox proportional hazards models were utilized. The performance of these models was assessed using discrimination, calibration, and reclassification. Results: A total of 117 individuals were enrolled. The mean follow-up time was 4.8 years, during which 35 patients (29.9 %) progressed to the composite renal outcomes. Male sex, baseline proteinuria, eGFR and globotriaosylsphingosine (Lyso-Gb3) were found to be independent risk factors for kidney progression by the Cox model, based on which a combined model containing those clinical variables and Lyso-Gb3 and clinical models including only clinical indicators were constructed. The two prediction models had relatively good performance, with similar model fit measured by R2 (59.8 % vs. 61.1 %) and AIC (51.54 vs. 50.08) and a slight increase in the C statistic (0.949 vs. 0.951). Calibration curves indicated closer alignment between predicted and actual renal outcomes in the combined model. Furthermore, subgroup analysis revealed that Lyso-Gb3 significantly improved the predictive performance of the combined model for kidney prognosis in low -risk patients with a baseline eGFR over 60 ml/min/1.73 m2 or proteinuria levels less than 1 g/d when compared to the clinical model. Conclusions: Lyso-Gb3 improves the prediction of kidney outcomes in FD patients with a low risk of progression, suggesting that these patients may benefit from early intervention to assist in clinical management. These findings need to be externally validated.

Introduction: Previous studies have shown that rituximab (RTX) and cyclic oral corticosteroid-cyclophosphamide (CTX) regimens have similar effects on Primary Membranous Nephropathy. However, no studies have compared RTX with an intravenous CTX regimen, which is more commonly used in China and requires fewer cumulative CTX doses. Methods: We prospectively assigned 141 PMN patients with baseline proteinuria ≥ 4 g/24 h, serum albumin < 30 g/L, and eGFR ≥ 30 mL/min × 1.73 m2 despite at least 3 months of treatment with ACEI and/or ARB to the RTX group (375 mg/m2 per injection per week × 4 injections) or to the CTX group (prednisone 0.8 mg/kg/d and intravenous CTX 500 mg/m2 per month until the total dose reached 6–8 g). The primary endpoint was defined as a combination of partial remission or complete remission at 12 months. Results: By the end of 12 months, 43 of 70 patients (61.43%) in the RTX group and 54 of 71 patients (76.06%) in the CTX group reached the primary endpoint(P=0.06). Significantly fewer patients in the RTX group achieved complete remission than the CTX group (14.29% vs. 33.80%, P=0.01). The adverse events rate was similar between the RTX group and the CTX group (28.57% vs. 40.85%, P=0.13). In subgroup analysis, we found that fewer patients from the RTX group achieved the primary endpoint than the CTX group (48.65% vs. 74.29%, P=0.03) among patients with massive proteinuria (urine protein ≥ 8 g/24 h). During the observational phase, 61 patients in the RTX group and 58 in the CTX group completed 24 months of follow-up, exhibiting similar remission rates (RTX vs. CTX: 75.41% vs. 68.97%, P=0.54). Conclusions: Our results show that the intravenous CTX regimen has similar safety and efficacy with higher rates of early complete remission than RTX in the treatment of PMN patients.

PURPOSE:Motion related artifact is a challenge for MRI, especially when imaging regions like the carotid artery where complex motion (abrupt and bulk motion) may occur. This study aims to develop a non-contact motion detection and correction system for carotid MRI using a markerless optical tracking system. METHODS:The proposed markerless optical tracking system consisted of a cross-line laser, an MRI-compatible camera and plastic holders mounted inside the scanner bore. The neck motion of the subject can be captured by monitoring the change of the projected laser position in real-time. The system was used to correct both abrupt motion and bulk motion for carotid MRI. The abrupt motion (e.g. coughing) was compensated by discarding the corrupted k-space lines and re-estimating the missing lines using SPIRiT algorithm. The bulk motion was corrected by phase adjustment of k-space lines according to the measured 1D-translational bulk motion (along anterior-posterior direction) and optimized in-plane translation parameters. Ten volunteers underwent carotid MRI with real-time neck motion detection and retrospective motion correction. Artery sharpness, vessel wall thickness and overall image quality score were compared between the motion-corrupted image and motion-corrected images of different correction strategies. RESULTS:Both the abrupt motion and the bulk motion during carotid scanning were successfully detected and corrected. The results of ten volunteers demonstrated significant improvement in carotid artery sharpness, vessel wall thickness measurement, and overall image quality score using the proposed markerless optical tracking system and motion correction strategies. CONCLUSION:The proposed markerless structured light based motion detection and correction system can sensitively detect both abrupt and bulk motion during carotid MR scans. By correcting for both abrupt and bulk motion, vessel wall delineation was improved in carotid MR images, which could potentially facilitate carotid plaque identification and atherosclerosis diagnosis in the future.

Purpose There is currently a lack of studies investigating long-term prognosis and the necessity of further rituximab (RTX) consolidation treatment for minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS). The aim of this study was to evaluate the efficacy of RTX for these diseases and to investigate whether a consolidation treatment can lower risks of relapse and reinforce long-term remission. Patients and Methods A retrospective study was conducted. The relapse and remission of 70 patients treated with 1 course of RTX treatment (4 infusions of 375 mg/m2) over a median follow-up time of 27 months (12–60 months) were analyzed. The rates of patients that were able to achieve non-relapse for a duration of 24 months between RTX consolidation therapy and non-consolidation therapy were compared. Results There were 67 cases (95.71%) of remission and 3 cases (4.29%) of non-remission. The average number of relapses decreased from 3.7±2.5 times before the treatment to 0.8±1.8 times after treatment (P <0.001). The average avannual number of relapses decreased from 1.3±1.2 times/year to 0.2±0.3 times/year (P <0.001). The results from the Cox proportional-hazards model showed that the risk of relapse in patients who received RTX non-consolidation treatment was significantly higher than those with consolidation treatment (odds ratios (OR) 20.9, 95% confidence intervals (CI) OR 5.7–75.7, p<0.001). The 24-month relapse-free rate was also significantly higher in patients with consolidation therapy compared with non-consolidation therapy (86.36% vs 25%, p<0.001). No adverse events were recorded. Conclusion RTX is highly effective in treating MCD and FSGS, and RTX consolidation therapy may be recommended to reinforce long-term remissions.

Objective To examine which factors are driving improvement in the Dialysis Facility Compare (DFC) star ratings and to test whether nonclinical facility characteristics are associated with observed longitudinal changes in the star ratings. Data Sources Data were collected from eligible patients in over 6,000 Medicare-certified dialysis facilities from three annual star rating and individual measure updates, publicly released on DFC in October 2015, October 2016, and April 2018. Study Design Changes in the star rating and individual quality measures were investigated across three public data releases. Year-to-year changes in the star ratings were linked to facility characteristics, adjusting for baseline differences in quality measure performance. Data Collection Data from publicly reported quality measures, including standardized mortality, hospitalization, and transfusion ratios, dialysis adequacy, type of vascular access for dialysis, and management of mineral and bone disease, were extracted from annual DFC data releases. Principal Findings The proportion of four- and five-star facilities increased from 30.0% to 53.4% between October 2015 and April 2018. Quality improvement was driven by the domain of care containing the dialysis adequacy and hypercalcemia measures. Additionally, independently owned facilities and facilities belonging to smaller dialysis organizations had significantly lower odds of year-to-year improvement than facilities belonging to either of the two large dialysis organizations (Odds Ratio [OR]: 0.736, 95% Confidence Interval [CI]: 0.631-0.856 and OR: 0.797, 95% CI: 0.723-0.879, respectively). Conclusions The percentage of four- and five-star facilities has increased markedly over a three-year time period. These changes were driven by improvement in the specific quality measures that may be most directly under the control of the dialysis facility.

Aims: It remains controversial to choose the optimal equation to estimate glomerular filtration rate (GFR) in chronic kidney disease (CKD) patients with diabetes. Materials and Methods: Two hundred and fifteen diabetic CKD patients and 192 non-diabetic CKD patients were enrolled in this study. Iohexol GFR, serum creatinine (SCr), and Cystatin C(CysC) were measured simultaneously for each patient. SCr- and CysC-based estimated GFR (eGFR) were calculated through eight equations, including three CKD-EPI equations, Revised Lund-Malmö study equation (RLM), CAPA equation, and three Full Age Spectrum (FAS) equations. Bias, precision, and accuracy were compared among eGFR equations with iohexol-GFR serving as measured GFR (mGFR). Independent predictive factors of accuracy were explored using multivariate logistic regression analysis. Results: In the diabetic group, CKD-EPISCr−CysC showed the best performance among three CKD-EPI equations (interquartile range of 13.88 ml/min/1.73 m2 and 30% accuracy of 72.56%). Compared to CKD-EPISCr−CysC, the other five equations did not significantly improve the performance of GFR estimates. Mostly, eGFR equations were less accurate in diabetic group than in non-diabetic group. Significant differences were found in different mGFR range (P < 0.001). The multivariate logistic regression analysis identified that BMI, mGFR, and diabetic kidney disease (DKD) status were independent predictors of accuracy of three equations in diabetic group. HbA1c was a predictor of accuracy of CKD-EPISCr and CKD-EPICysC in diabetic group. Conclusions: This study showed that eGFR equations were less accurate in the diabetic group than in the non-diabetic group. CKD-EPIScr−CysC had the best performance among CKD-EPI equations in Chinese diabetic CKD patients. The other five equations did not significantly improve the performance of GFR estimates. BMI, mGFR, DKD status, and HbA1c were independent factors associated with accuracy in eGFR equations.

Patients with Idiopathic membranous nephropathy (IMN) have various outcomes. The aim of this study is to construct a tool for clinicians to precisely predict outcome of IMN.

PURPOSE:Fluorouracil, leucovorin, irinotecan, oxaliplatin (FOLFIRINOX) and gemcitabine plus nab-paclitaxel (GEM-N) have shown a significant survival benefit for the treatment of metastatic pancreatic cancer. The objective of this study was to assess the cost-effectiveness of FOLFIRINOX versus GEM-N for treating metastatic pancreatic cancer based on the PRODIGE and MPACT trials.METHODS:A decision model was performed to compare FOLFIRINOX with GEM-N. Primary base case data were identified from PRODIGE and MPACT trials. Costs were estimated and incremental cost-effectiveness ratio (ICER) was calculated at West China Hospital, Sichuan University, China. Survival benefits were reported in quality-adjusted life-years (QALY). Finally, sensitive analysis was performed by varying potentially modifiable parameters in the model.RESULTS:The base-case analysis showed that FOLFIRINOX cost $37,203.75 and yielded a survival of 0.67 QALY, and GEM-N cost $32,080.59 and yielded a survival of 0.51 QALY in the entire treatment. Thus, the ICER of FOLFIRINOX versus GEM-N was $32,019.75 per QALY gained.CONCLUSIONS:The GEM-N regimen was more cost-effective compared with the FOLFIRINOX regimen for the treatment of metastatic pancreatic cancer from a Chinese perspective.

The E3805 (CHAARTED) study found that docetaxel combined with androgen-deprivation therapy (ADT) significantly improved overall survival of patients with metastatic hormone-sensitive prostate cancer. This study aims to determine whether docetaxel combined with ADT is a cost-effective strategy for advanced prostate cancer in China. According to the E3805 study, two groups (docetaxel + ADT and ADT alone) and three health states [progression-free survival (PFS), progressive disease (PD) and death] were analysed in a Markov model. All medical costs were calculated from the Chinese societal perspective. Quality-adjusted life year (QALY) and incremental cost-effectiveness ratios (ICERs) were applied as the primary outcome. Overall, the addition of docetaxel was estimated to increase the cost by $12 816.93, with a gain of 0.48 QALY. Additionally, for patients with high-volume disease, the increased cost and effectiveness were $14 627.75 and 0.69 QALYs in docetaxel + ADT group versus the ADT alone group, and the ICER was $21 199.63 per QALY. These ICERs are far more than the commonly accepted willingness-to-pay (WTP) threshold of $20 301 per QALY in China. In spite of longer survival time, docetaxel combined with ADT is not a recommended cost-effective treatment for metastatic hormone-sensitive prostate cancer in the Chinese setting.

No standard treatment has been accepted widely for the first-/second-line therapy for advanced gastric cancer (AGC). The current study aimed to determine a preferred strategy between FOLFIRI (fluorouracil, leucovorin, and irinotecan) and ECX (epirubicin, cisplatin,and capecitabine) for AGC from the cost-effectiveness perspective. According to a French intergroup study, two groups (ECX arm and FOLFIRI arm) and three health states (progression-free survival (PFS), progressive disease (PD) and death) were analyzed in the current Markov model. All the medical costs were calculated from a Chinese societal perspective. Although FOLFIRI was an acceptable first-line therapy in the treatment of AGC with a better time-to treatment failure (TTF) compared to ECX, ECX arm (ECX followed by FOLFIRI) gained 0.08 quality-adjusted life months (QALMs) more effectiveness benefit compared with FOLFIRI arm (FOLFIRI followed by ECX). Additionally, a lower cost was found in ECX arm ($23,813.13 versus $24,983.70). Hence, the strategy of FOLFIRI arm is dominated by ECX arm ($4,125.8 per QALM in FOLIRI arm; $3,879.724 per QALM in ECX arm). ECX followed by FOLFIRI was a preferred strategy with more effectiveness and lower cost compared with FOLFIRI followed by ECX for the treatment of AGC.

It is important to find better treatments for diabetic nephropathy (DN), a debilitating renal complication. Targeting early features of DN, including renal extracellular matrix accumulation (ECM) and glomerular hypertrophy, can prevent disease progression. Here we show that a megacluster of nearly 40 microRNAs and their host long non-coding RNA transcript (lnc-MGC) are coordinately increased in the glomeruli of mouse models of DN, and mesangial cells treated with transforming growth factor-β1 (TGF- β1) or high glucose. Lnc-MGC is regulated by an endoplasmic reticulum (ER) stress-related transcription factor, CHOP. Cluster microRNAs and lnc-MGC are decreased in diabetic Chop-/- mice that showed protection from DN. Target genes of megacluster microRNAs have functions related to protein synthesis and ER stress. A chemically modified oligonucleotide targeting lnc-MGC inhibits cluster microRNAs, glomerular ECM and hypertrophy in diabetic mice. Relevance to human DN is also demonstrated. These results demonstrate the translational implications of targeting lnc-MGC for controlling DN progression.

Background. The study investigates the occurrence, severity, and outcomes of acute kidney injury (AKI) in octogenarians following heart valve surgery. Methods. All patients, age >80 years, not on dialysis and without kidney transplant, undergoing heart valve replacement at Mayo Clinic, Rochester, in the years 2002-2003 were enrolled. AKI was diagnosed based on AKIN criteria. Results. 209 octogenarians (88.0% aortic valve, 6.2% mitral valve, 1.0% tricuspid valve, and 4.8% multivalve) with (58.4%) and without CABG were studied. 34 (16.3%) had preexisting CKD. After surgery, 98 (46.8%) developed AKI. 76.5% of the AKI were in Stage 1, 9.2% in Stage 2, and 14.3% in Stage 3. 76.5% CKD patients developed AKI. Length of hospital stay was longer for AKI patients. More AKI patients were discharged to care facilities. Patient survival at 30 days and 1 year for AKI versus non-AKI was 88.8 versus 98.7%, p=0.003, and 76.5 versus 88.3%, p=0.025, respectively. With follow-up of 3.94±0.28 years, Kaplan-Meier analysis showed a reduced survival for AKI octogenarians. Preexisting CKD and large volume intraoperative fluid administration were independent AKI predictors. Conclusions. Nearly half of the octogenarians developed AKI after valve replacement surgery. AKI was associated with significant functional impairment and reduced survival.

History of the present illness The patient was healthy until 4 weeks prior (mid-July 2012) to her transfer, when she developed sudden-onset abdominal pain, right flank pain, and anorexia (Figure 1). Evaluation at a local emergency department, including an abdominal ultrasound, was reportedly normal. The impression was possible renal colic and constipation. She was discharged with acetaminophen and stool softener. Approximately 3 weeks later, she presented to a local clinic with progressive general and lower extremity weakness, left-eye blurry vision, cough, chest congestion, and palpitations. She was diagnosed with viral syndrome and given eye drops. Three days later, her symptoms worsened. She developed dyspnea and bilateral blurry vision. She was rushed to the emergency department, where she was hypertensive (blood pressure [BP] 180–200/130 mm Hg), tachycardic (150 beats/minute), and diaphoretic. Within hours, she became hypoxic and required intubation. Her chest radiograph showed diffuse bilateral infiltrates. Laboratory studies revealed hemoglobin of 9.2 gm/dl (reference value 12–15.5), leukocytes of 13.7 10/liter (reference value 3.5–10.5), platelet count of 154 10/liter (reference value 150–450), reticulocytes of 4.38% (reference value 0.60–1.83%), prothrombin time of 16.7 seconds (reference value 9.5–13.8), serum creatinine of 4.8 mg/dl (reference value 0.6–1.1), complement C3 of 92 mg/dl (reference value 75–175), and C4 of 8 mg/dl (reference value 14–40). Urinalysis showed red blood cells of 10–20/high-power field and proteinuria of 300 mg/ dl. Human immunodeficiency virus, hepatitis B, and hepatitis C were negative. Transthoracic echocardiogram showed a left ventricular ejection fraction of 30%, and a kidney ultrasound with Doppler study showed normalsized kidneys with nonspecific changes in the renal arteries. She was provisionally diagnosed with renal failure due to rapidly progressive glomerulonephritis. Pulse steroids (intravenous [IV] methylprednisolone 1 gm/day), plasma exchange, and dialysis were initiated. After 2 runs of hemodialysis, she was extubated and transferred to the Mayo Clinic the following day. The evening before transfer, antineutrophil cytoplasmic antibody (ANCA) and anti–glomerular basement membrane (anti-GBM) studies returned negative. A computed tomography (CT) angiogram and renal biopsy were performed; the images and tissue sample were forwarded to our institution for interpretation.

End-of-life decision-making is a complex process that can be extremely challenging. We describe a 42-year-old woman in an irreversible coma without an advance directive. The case serves to illustrate the complications that can occur in end-of-life decision-making and challenges in resolving difficult futility disputes. We review the role of advance directives in planning end-of-life care, the responsibility and historical performance of patient surrogates, the genesis of futility disputes, and approaches to resolving disputes.