Bendamustine and prednisone in combination with bortezomib (BPV) in the treatment of patients with relapsed or refractory multiple myeloma and light chain-induced renal failure

Introduction

Serious renal failure represents a severe complication of multiple myeloma (MM), with an estimated 25–50 % of patients being affected. Both bortezomib and bendamustine have been identified as quickly acting, effective and well-tolerated drugs and might therefore constitute an adequate combination regimen for patients presenting with light chain-induced renal failure.

Methods

Between March 2005 and March 2013, 36 patients with relapsed/refractory MM and light chain-induced renal failure (creatinine clearance <60 ml/min) were treated with bendamustine 60 mg/m² on days 1 and 2, bortezomib 1.3 mg/m² on days 1, 4, 8 and 11 and prednisone 100 mg on days 1, 2, 4, 8 and 11 (BPV). Patients were divided according to severity of renal impairment into group A (n = 20) with moderate or severe renal dysfunction (eGFR 15–59 ml/min) and group B (n = 16) with renal failure/dialysis (eGFR <15 ml/min).

Results

Twenty-four patients (67 %) responded with three CR, three nCR, six VGPR and 12 PR. Six patients had minor response, two stable and four progressive disease. With a median follow-up period of 22 months, median progression-free survival (PFS) and overall survival (OS) for patients of group A were 10 and 25 months, respectively. This outcome was significantly better compared to patients of group B with a median PFS and OS of 3 and 7 months, respectively. Eleven patients showed a CRrenal, five a PRrenal and 15 a MRrenal.

Summary

These results indicate that this BPV combination is feasible, effective and well tolerated in patients with relapsed/refractory MM and light chain-induced renal failure.     

Combined bendamustine, prednisone and bortezomib (BPV) in patients with relapsed or refractory multiple myeloma

Introduction

Bortezomib (Velcade^®) is a proteasome inhibitor that has shown important clinical efficacy either as a single agent or in combination with other cytostatic agents in multiple myeloma (MM). In the present protocol, bortezomib was combined with other active substances like bendamustine and prednisone (BPV), in order to assess the efficacy and toxicity of the combination therapy in patients with relapsed or refractory MM.

Methods

Between January 2005 and December 2011, 78 patients with relapsed or refractory MM were treated with bendamustine 60 (?120) mg/m² on days 1 and 2, bortezomib 1.3 mg/m² on days 1, 4, 8 and 11, and prednisone 100 mg on days 1, 2, 4, 8 and 11. The median number of prior therapies was 2 with a wide range of 1–9. Thirty-three patients had pre-existing severe thrombocytopenia and/or neutropenia (WHO grade 3 or 4).

Results

A median number of two (range 1–7) BPV treatment cycles were given to the patients. The majority of the patients (n = 54; 69 %) responded after at least one cycle of chemotherapy with 3 CR, 10 nCR, 10 VGPR and 31 PR. Median PFS and OS for patients without severe hematological toxicities due to previous treatments (n = 45) were 11 and 50 months, respectively. Outcome for these patients was significantly better than that for patients with severe hematological toxicities (grade 3 or 4, n = 33) with a PFS, and OS of 3 months (p < 0.05) and 5 months (p < 0.001), respectively. The regimen was well tolerated with few significant side effects in patients without severe hematological toxicities due to previous treatments.

Summary

These results indicate that the combination of bortezomib, bendamustine and prednisone is well tolerated in patients with relapsed or refractory MM.     

Successful treatment of patients with newly diagnosed/untreated multiple myeloma and advanced renal failure using bortezomib in combination with bendamustine and prednisone

Purpose

Renal failure is a frequent complication of multiple myeloma (MM) and, if present at diagnosis, a considerable risk factor for outcome. Treatment with chemotherapy and/or new agents may result in recovery of renal function in up to 50?% of patients. The window of opportunity to reverse renal impairment is, however, rather small, making an immediate and highly active treatment strategy mandatory. Bortezomib as well as bendamustine has been demonstrated to be potent drugs in the treatment of MM.

Methods

A total of 18 patients with newly diagnosed/untreated MM and renal insufficiency (GFR?Results The majority of them (n?=?15; 83?%) responded after at least one cycle of chemotherapy with three sCR, five nCR, five VGPR, and two PR. With a median follow-up of 17?months, PFS at 18?months was 57?% and OS was 61?%. The myeloma protein decreased rapidly, reaching the best response after the first cycle in four and after the second cycle in additional seven patients. Thirteen patients (72?%) improved their renal function after treatment.

Conclusion

We conclude that the combination of bortezomib, bendamustine, and prednisone is effective and well tolerated in patients with a newly diagnosed MM and renal failure.     

How to determine bortezomib-based regimen for elderly patients with multiple myeloma: PAD versus CBd, an observational study

Background

This was an open-label, observational, prospective assessment. We conducted an analysis of the impact of bortezomib-based therapy (PAD: bortezomib, doxorubicin, high-dose dexamethasone vs. CBd: cyclophosphamide bortezomib, low-dose dexamethasone) on the survival rates and adverse events in elderly patients with newly diagnosed multiple myeloma (MM).

Methods

Out of 303 patients, 128 received the PAD regimen and the other 175 patients received the CBd induction therapy (age 65–89 years). Baseline patient characteristics between the two cohorts were balanced in age (P = 0.69), international staging system (ISS) prognostic stages (P = 0.90), serum calcium (P = 0.70), and serum creatinine (P = 0.52).

Results

Overall response (OS) after the induction chemotherapy was achieved in 214 of 303 patients (70.6 %), with no significant differences observed between the two treatment groups (71.9 vs. 69.7 %, P = 0.68). Patients with ISS stage 2 reached the same 5-year OS advantages compared to patients with ISS stage 1, because they received bortezomib-based PAD or CBd treatments. Patients receiving CBd protocol gained similar satisfactory progression-free survival (PFS) results when compared to the PAD regimen group: PFS at 5 years reached 58.2 versus 58.9 % (P = 0.85). Five-year OS in the CBd arm had significant advantages compared to the PAD group, 79.9 versus 49.9 % (P < 0.05). The overall safety profiles showed that 26 of 128 (20.3 %) patients died in the PAD arm, while 13 of 175 patients died (7.4 %) in the CBd group (P < 0.01). Similarly, the PAD arm had a higher serious infection rate than that of the CBd arm (39.2 vs. 13.1 %, P < 0.01).

Conclusions

Bortezomib benefits elderly patients with newly diagnosed MM; they achieve satisfactory treatment responses and survival advantages. Further, patients treated with CBd have superior treatment advantages, with a predictable safety profile, when compared to the PAD regimen.     

Age-related fat deposition in multifidus muscle could be a marker for nonalcoholic fatty liver disease

Background

Although nonalcoholic fatty liver disease (NAFLD) is associated with visceral obesity, the relationship between visceral fat accumulation and skeletal muscle steatosis in patients with NAFLD has not been established. We evaluated: (1) the relationship between multifidus muscular tissue steatosis, visceral fat accumulation, and biochemical data in a cross-sectional study, and (2) the influence of weight reduction on multifidus muscular tissue steatosis in a longitudinal study.

Methods

Three hundred thirty-three NAFLD patients were enrolled. Hepatic steatosis, visceral fat area, and the multifidus muscle/subcutaneous fat attenuation ratio (MM/F ratio) were evaluated by computed tomography. To evaluate how weight reduction produced by diet and exercise affected the MM/F ratio, changes in the MM/F ratio were compared between weight reduction and non-weight reduction groups.

Results

There was a gender difference in MM/F ratios. The MM/F ratio was significantly correlated with age (male r = 0.613, P < 0.01; female r = 0.440, P < 0.01). The MM/F ratio was positively correlated with visceral fat area (male: r = 0.262, P < 0.01; female: r = 0.214, P < 0.01). A decrease in the MM/F ratio, concomitant with reduced visceral fat accumulation, led to alleviation of hepatic steatosis in 20 patients with weight reduction, but not in 22 patients without weight reduction.

Conclusions

The MM/F ratio was closely related to aging and visceral fat accumulation. The MM/F ratio was improved by weight reduction, indicating that fat accumulation in the multifidus muscle evaluated by computed tomography might be a therapeutic indicator of NAFLD.     

Cardiac autonomic neuropathy predicts renal function decline in patients with type 2 diabetes: a cohort study

Aims/hypothesis

The aim of this work was to assess the impact of cardiac autonomic neuropathy (CAN) on the development and progression of chronic kidney disease (CKD) in patients with type 2 diabetes.

Methods

We conducted a cohort study in adults with type 2 diabetes. Patients with end-stage renal disease were excluded. CKD was defined as the presence of albuminuria (albumin/creatinine ratio GFR >?3.4 mg/mmol) or an estimated (eGFR) <?60 ml min^?1 1.73 m^?2. CKD progression was based on repeated eGFR measurements and/or the development of albuminuria. CAN was assessed using heart rate variability.

Results

Two hundred and four patients were included in the analysis. At baseline, the prevalence of CKD and CAN was 40% and 42%, respectively. Patients with CAN had lower eGFR and higher prevalence of albuminuria and CKD. Spectral analysis variables were independently associated with eGFR, albuminuria and CKD at baseline. After a follow-up of 2.5 years, eGFR declined to a greater extent in patients with CAN than in those without CAN (?9.0?±?17.8% vs ?3.3?±?10.3%, p?=?0.009). After adjustment for baseline eGFR and baseline differences, CAN remained an independent predictor of eGFR decline over the follow-up period (β?=??3.5, p?=?0.03). Spectral analysis variables were also independent predictors of eGFR decline.

Conclusions/interpretation

CAN was independently associated with CKD, albuminuria and eGFR in patients with type 2 diabetes. In addition, CAN was an independent predictor of the decline in eGFR over the follow-up period. CAN could be used to identify patients with type 2 diabetes who are at increased risk of rapid decline in eGFR, so that preventative therapies might be intensified.     

Experience with daptomycin daily dosing in ICU patients undergoing continuous renal replacement therapy

Purpose

For critically ill patients undergoing continuous renal replacement therapy (CRRT), daptomycin dosing recommendations are scarce. We, therefore, retrospectively assessed routinely measured daptomycin plasma concentrations, daptomycin dose administered and microbiological data in 11 critically ill patients with Gram-positive infections that had received daptomycin once daily.

Methods

The retrospective analysis included critically ill patients treated at the intensive care unit (ICU) who had daptomycin plasma concentrations measured.

Results

Daptomycin dose ranged from 3 to 8 mg/kg/q24 h in patients undergoing CRRT (n = 7) and 6 to 10 mg/kg/q24 h in patients without CRRT (n = 4). Peak and trough concentrations showed a high intra- and inter-patient variability in both groups, independent of the dosage per kg body weight. No drug accumulation was detected in CRRT patients with once-daily daptomycin dosing. Causative pathogens were Enterococcus faecium (n = 6), coagulase-negative Staphylococcus (n = 2), Staphylococcus aureus (n = 2) and unknown in one patient. Microbiological eradication was successful in 8 of 11 patients. Two of three patients with unsuccessful microbiological eradication and fatal outcome had an Enterococcus faecium infection.

Conclusion

In critically ill patients undergoing CRRT, daptomycin exposure with once-daily dosing was similar to ICU patients with normal renal function, but lower compared to healthy volunteers. Our data suggest that daptomycin once-daily dosing is appropriate in patients undergoing CRRT.     

Renal dysfunction and hypophosphatemia during long-term lamivudine plus adefovir dipivoxil therapy in patients with chronic hepatitis B

Background

Renal dysfunction and Fanconi’s syndrome associated with hypophosphatemia caused by long-term administration of low-dose adefovir dipivoxil (ADV) has been reported in recent years. The aim of this retrospective study was to determine the incidence and factors associated with renal dysfunction and hypophosphatemia in patients with hepatitis B infection on long-term treatment with ADV and lamivudine (LAM).

Methods

The study subjects were 292 patients treated with 10 mg/day ADV and 100 mg/day LAM for more than 6 months. We evaluated estimated glomerular filtration rate (eGFR), serum creatinine and serum phosphate level at the start of ADV and every 6 months.

Result

During a median treatment duration of 64 months, 28 (9.6 %) patients developed renal impairment (defined as eGFR < 50 ml/min/1.73 m²), and 73 (27.1 %) developed hypophosphatemia, including 14 with persistent hypophosphatemia. The cumulative incidences of renal impairment at 1, 3, and 5 years were 1.4, 7.5, 10.5 %, respectively, and those of hypophosphatemia were 6.8, 20.6, 26.7 %, respectively. Multivariate analysis identified old age, liver cirrhosis and hypertension as determinants of renal impairment, and male sex, HCC, low baseline serum phosphate as determinants of hypophosphatemia. Three of the 14 patients with persistent hypophosphatemia developed Fanconi’s syndrome; their serum creatinine level remained normal, but eGFR was lower than at baseline.

Conclusion

Long-term treatment of hepatitis B with low-dose (10 mg/day) ADV and LAM can potentially cause renal impairment and hypophosphatemia. We advocate regular monitoring of serum phosphate and evaluation of eGFR, in addition to serum creatinine, in such patients.     

A temporary loop ileostomy affects renal function

Purpose

The purpose of this study was to evaluate renal morbidity after a temporary loop ileostomy and to identify possible preoperative risk factors.

Method

Consecutive patients at four hospitals serving 1,520,000 inhabitants who received a temporary loop ileostomy and underwent subsequent closure were identified and retrospectively studied from 1 January 2007 until 28 February 2010. Serum creatinine levels were obtained 1 week before index surgery and 1 week before closure of the loop ileostomy. Estimated glomerular filtration rate (eGFR) was calculated using the CKD-EPI formula.

Results

Three hundred eight patients with median age of 64 were identified. The indication for the loop ileostomy was colorectal cancer (226), inflammatory bowel disease (41), diverticulosis (8), and other conditions (33). Median time until closure was 161 days (3–873). There was a decrease in eGFR at time of closure (89 vs. 83; p?p?Conclusions This study found that a loop ileostomy is associated with a reduced renal function for most patients, especially for older and hypertensive patients. This should be considered before constructing a loop ileostomy, and perhaps another stoma should be chosen if possible in patients at risk. Evaluation of medications before discharge and early and frequent postoperative follow-up could also reduce the risk of a reduced renal function.     

The Choi response criteria for inferior vena cava tumor thrombus in renal cell carcinoma treated with targeted therapy

Objectives

To evaluate the prognostic significance of the Choi criteria for assessing the responses of a renal mass and inferior vena cava (IVC) tumor thrombus in patients with renal cell carcinoma (RCC) receiving targeted therapy.

Materials and methods

We reviewed the medical records of 22 patients diagnosed with RCC and IVC thrombus between 2005 and 2012. The efficacy of targeted therapy in renal mass and IVC tumor thrombus was evaluated using response evaluation criteria in solid tumors (RECIST) and Choi criteria, respectively. Overall survival was estimated, and the prognostic significance of each variable was estimated using Cox proportional-hazards regression modeling.

Results

There were no significant differences in overall survival between patients with partial response (PR) and nonresponse according to RECIST criteria (19.3 vs 43 months; p = 0.212) or Choi criteria (9.0 vs 23.3 months; p = 0.109) in primary tumor. Regarding the response of IVC tumor thrombi, according to Choi criteria, nine patients (40.9 %) demonstrated PR and longer survival than patients with stable disease (7.2 vs 23.3 months; p = 0.014). In multivariable analysis, response to IVC thrombus according to Choi criteria was the only significant predictive factor. Patients with IVC thrombus who demonstrate the PR according to Choi criteria were at 0.35-fold greater overall risk of death compared with patients who did not demonstrate this response (p = 0.043).

Conclusions

A response according to Choi criteria in IVC tumor thrombus was an independent prognostic predictor in patients with RCC and IVC thrombus who receive targeted therapy.     

Copeptin, a surrogate marker for arginine vasopressin, is associated with declining glomerular filtration in patients with diabetes mellitus (ZODIAC-33)

Aim/hypothesis

Arginine vasopressin (AVP), the hormone important for maintaining fluid balance, has been shown to cause kidney damage in rodent models of diabetes. We investigated the potential role of AVP in the natural course of kidney function decline in diabetes in an epidemiological study.

Methods

Plasma copeptin, a surrogate for AVP, was measured in baseline samples from patients with type 2 diabetes treated in primary care and included in the Zwolle Outpatient Diabetes project Integrating Available Care (ZODIAC) cohort.

Results

Samples from 1,328 patients were available; 349 were analysed separately because they used renin–angiotensin–aldosterone system inhibition (RAASi), which influences albumin/creatinine ratio (ACR) and estimated (e)GFR. In the other 979 patients (46% men, age 68 years [58–75], ACR 1.8 mg/mmol [0.9–5.7], eGFR 67?±?14 ml min^?1 1.73 m^?2) baseline copeptin (5.3 pmol/l [3.2–9.5]) was significantly associated with log _e [ACR] and eGFR, even after adjustment for sex, age and risk factors for kidney function decline (standardised [std] β 0.13, p?<?0.001, std β ?0.20, p?<?0.001 respectively). Follow-up data were available for 756 patients (6.5 years [4.1–9.6]). Baseline copeptin was associated with increase in ACR (std β 0.09, p?=?0.02), but lost significance after adjustment (std β 0.07, p?=?0.08). Copeptin was associated with a decrease in eGFR after adjustment (std β ?0.09, p?=?0.03). The strength of the association of copeptin with change in eGFR was stronger than that of established risk factors for kidney function decline (e.g. BMI, HbA_1c). In patients who used RAASi there was a significant association between baseline copeptin and ACR and eGFR, but not with change in ACR and eGFR.

Conclusions/interpretation

In patients with diabetes not using RAASi a higher baseline copeptin concentration is significantly associated with higher baseline ACR and lower eGFR values and with a decline in eGFR during follow-up. This last association is independent of, and stronger than, most traditional risk factors for kidney function decline.     

Renal impairment and coronary collaterals in patients with acute coronary syndrome

Objective

We aimed to elucidate the relationship between mild-to-moderate renal impairment and the development of coronary collateral vessels (CCV) in patients with acute coronary syndrome (ACS).

Methods

We enrolled 461 patients with ACS who underwent coronary angiography for the first time. The development of CCV was assessed with the Rentrop score. Kidney function was classified according to the estimated glomerular filtration rate (eGFR). The Gensini score was used to show the extent of atherosclerosis.

Results

The mean eGFR value was 89.9?±?24.3 U/l for patients with no development of collaterals and 82.7?±?20.5 for patients who had CCV. The mean age was 59?±?11 years and 349 patients (75.7?%) were male. Rentrop classifications 1-2-3 (presence of CCV) were determined in 222 (48.1?%) patients. The presence of CCV was significantly associated with low levels of eGFR (p?=?0.001), increased serum creatinine levels (p?=?0.034), high levels of serum albumin (0.036), and the Gensini score (p?<?0.001). Multivariate analysis showed that the Gensini score was an independent predictor of the presence of CCV (OR?=?1.090, 95?% CI: 1.032–1.151, p?=?0.002).

Conclusion

We suggest that the association between mild-to-moderate renal impairment and the presence of CCV may be explained by increased myocardial ischemia and severe CAD.     

Everolimus-based immunosuppression in liver transplant recipients: a single-centre experience

Purpose

Everolimus, a mammalian target of rapamycin inhibitor, has been shown to reduce growth factor-mediated cell proliferation, but data regarding its effectiveness and impact on renal function and recurrence of hepatocellular carcinoma (HCC) in liver transplant (LT) recipients are limited.

Methods

We evaluated LT recipients with a calcineurin inhibitor (CNI)-based immunosuppression regimen in whom everolimus treatment was initiated. The changes in laboratory data, including glomerular filtration rate (GFR), compared to the baseline (i.e. the day of everolimus conversion), were assessed.

Results

Totally, 44 consecutive patients (32 men, age 55 ± 7 years) were commenced on everolimus [indications: renal dysfunction post-LT (16 patients, group 1); prevention of HCC recurrence (21 patients) or others (7 patients), group 2] at 6 months (range 1–206) post-LT. After 48 (range 12–76) months, all patients were alive without any rejection episodes. Compared to group 2 patients, group 1 patients had significantly greater improvement in renal function (DGFR: 12 ± 5 vs. ?0.4 ± 0.2 ml/min, p = 0.02). GFR at baseline (OR 0.08, p = 0.002) and the combination of everolimus + MMF (OR 0.14, p = 0.024) were the factors independently associated with improvement in renal function. Finally, HCC recurrence was observed less frequently in the everolimus group of patients (n = 21) compared to the CNI-historical control group (n = 22) with HCC before LT [0/21 (0 %) vs. 4/22 (18.5 %), log rank p = 0.055), although the two groups of recipients had similar baseline characteristics and follow-up.

Conclusions

Everolimus is effective and is associated with low rates of HCC recurrence and improvement of renal function in LT recipients.     

Hyperuricemia is associated with progression of chronic kidney disease in patients with reduced functioning kidney mass

Background and objectives

Hyperuricemia plays a major role in the development and progression of chronic kidney disease (CKD). Many large observational studies have indicated that increased serum uric acid level predicts the development and progression of CKD in some population, however this hypothesis has not been yet studied in patients with reduced renal mass.

Randomized Pilot Study: Effects of an Exercise Programme and Leucine Supplementation in Patients with Cirrhosis

Background

Physical exercise could improve functional limitations, muscle mass, and health-related quality of life (HRQoL) in patients with cirrhosis.

Aim

The purpose of this study was to evaluate the efficacy and safety of an exercise programme and leucine supplementation to increase exercise capacity, muscle mass, and HRQoL in patients with cirrhosis.

Patients and Methods

Seventeen outpatients with cirrhosis were randomized to an exercise group (n = 8) or a control group (n = 9) in a pilot study. The programme of moderate exercise was performed for 12 weeks under supervision of a physiotherapist. All patients received oral leucine (10 g/day) during the study. At baseline and at the end of the study, we determined exercise capacity (6-min walk and 2-min step tests), anthropometric measurements, and HRQoL by Short Form-36 (SF-36) questionnaire. We also analyzed safety regarding complications of cirrhosis, liver and renal function, inflammatory response and oxidative stress.

Results

In the exercise group, exercise capacity improved, as shown by the increase in the 6-min walk test from 365 (160–420) to 445 m (250–500) (p = 0.01), and in the 2-min step test (p = 0.02). Lower thigh circumference also increased, from 41 (34–53) to 46 cm (36–56) (p = 0.02), and the domains of SF-36 general health (p = 0.03), vitality (p = 0.01) and social function (p = 0.04) improved significantly. In the control group, no statistically significant changes were observed in any of the parameters. We did not observe complications of cirrhosis in either group during the study.

Conclusions

A programme of moderate physical exercise together with leucine supplements in patients with cirrhosis is safe and improves exercise capacity, leg muscle mass and HRQoL.     

The clinicopathologic characteristics of granulomatosis with polyangiitis (Wegener’s): a retrospective study of 45 patients in Korea

Objectives

The aim of this study was to determine the clinicopathologic characteristics of granulomatosis with polyangiitis (Wegener’s) (GPA) in Korean patients.

Methods

The medical records of 45 patients with GPA treated in a single tertiary referral hospital were retrospectively analyzed with respect to clinical manifestations, including histology, ANCA positivity, disease stage, and disease activity. Patients were categorized into granulomatous, vasculitic, or mixed form based on an immunopathologic scoring system of granulomatous–vasculitic activity.

Results

Thirty-one patients (68.9 %) showed ANCA positivity (C-ANCA/P-ANCA, 42.2 %/20.0 %, proteinase-3 (PR3) ANCA/myeloperoxidase (MPO) ANCA, 44.1 %/16.1 %), and these patients (female 48.4 %) were found to be associated with a higher frequency of renal involvement (51.6 vs. 7.1 %, p = 0.004), elevated serum creatinine (29.0 vs. 0 %, p = 0.018), and higher mortality (29 vs. 7.1 %, p = 0.041) than ANCA-negative patients. Thirty-three patients (73.3 %, female 60.6 %) had the granulomatous form, whereas 8.9 and 17.8 % had the vasculitic and mixed forms, respectively. Patients with the granulomatous form were diagnosed earlier in their lives (mean age 51.2 vs. 62.3, p = 0.002) and had a lower frequency of renal involvement (21.2 vs. 100 %, p = 0.005) compared with those with the vasculitic form. Initial remission (69.7 vs. 25.0 %) and relapse (60.8 vs. 0 %) rates were higher for the granulomatous than for the vasculitic form.

Conclusions

Taken together, in Korean patients with GPA, the granulomatous form was predominant and associated with a younger age at diagnosis and a lower frequency of renal involvement than the vasculitic form. ANCA positivity was found in 68.9 % and associated with renal involvement and higher mortality.     

Preventive effect of oral nicorandil on contrast-induced nephropathy in patients with renal insufficiency undergoing elective cardiac catheterization

This study aims to investigate the preventive effect of oral nicorandil on contrast-induced nephropathy (CIN) in patients with renal insufficiency undergoing elective cardiac catheterization. A total of 240 patients with an estimated glomerular filtration rate (eGFR) of 60 mL/min or less, who were undergoing elective cardiac catheterization, were randomly assigned to nicorandil group (n = 120, 10 mg nicorandil, three times daily from 2 days before to 3 days after procedure) or control group (n = 120, matching placebo as the same method). The primary endpoint was the incidence of CIN defined as 25 % increase in serum creatinine (SCr) from baseline or 44 μmol/L (0.5 mg/dL) increase in absolute value within 72 h after exposure to contrast medium. The secondary endpoints were: (1) the changes of SCr, Cystatin-C (Cys-C) and eGFR within 72 h; (2) major adverse events (MACE) occurring within 30 days. Baseline characteristics of the patients in the two groups were similar. The incidence of CIN was significantly lower in nicorandil group compared with control group (6.67 vs. 17.5 %, P = 0.017). Compared with the control group, nicorandil group tended to have a lower SCr and Cys-C levels as well as a higher eGFR at 48 h after the procedure (all P < 0.05). There was no difference about the incidence of MACE within 30 days between nicorandil group and control group (4.16 vs. 5.83 %, P = 0.767). Multivariate logistic analysis showed that nicorandil was an independent protective factor against CIN (OR = 0.260, 95 % CI = 0.1–0.676, P = 0.006). Therefore, we concluded that oral nicorandil was associated with a decline in the incidence of CIN in patients with renal insufficiency undergoing elective cardiac catheterization.     

Efficacy of Transjugular Intrahepatic Portosystemic Shunt with Adjunctive Embolotherapy with Cyanoacrylate for Esophageal Variceal Bleeding

Background

Transjugular intrahepatic portosystemic shunt (TIPS) with adjunctive embolotherapy has recently been reported to be effective in the prevention of variceal hemorrhage of cirrhotic patients. However, further investigation of its long-term efficacy is still needed.

Aim

To examine the rebleeding, survival, and hepatic encephalopathy (HE) after treatment with TIPS alone and TIPS with adjunctive embolotherapy using cyanoacrylate for esophageal variceal bleeding.

Methods

Patients with refractory to endoscopic therapy for esophageal variceal bleeding were enrolled. TIPS was performed in 101 patients with adjunctive embolotherapy (n = 53) or alone (n = 48) between January 2006 and December 2011. Chart reviews were performed to determine rebleeding, survival rates, and the incidence of HE.

Results

Recurrent hemorrhage occurred in 12 (11.9 %) patients during the mean follow-up periods of 35.8 months. Rebleeding was observed in 9/48 (18.8 %) patients in TIPS alone group and 3/53 (5.7 %) patients in TIPS with adjunctive embolotherapy group (p = 0.042). Death occurred in 30 patients during follow-up (TIPS alone: n = 16, TIPS with adjunctive embolotherapy: n = 14, p = 0.447). Twenty-six episodes of HE occurred in 18 patients in TIPS alone group and 16 episodes occurred in 10 patients in TIPS with embolotherapy group. The probability of HE was significantly higher in TIPS alone group than in TIPS with embolotherapy group (p = 0.019).

Conclusions

TIPS with adjunctive embolotherapy with cyanoacrylate is relatively safe and effective, with a lower rebleeding and HE incidence in comparison of TIPS alone.     

Anti-CADM-140/MDA5 autoantibody titer correlates with disease activity and predicts disease outcome in patients with dermatomyositis and rapidly progressive interstitial lung disease

Objectives

We examined the relationship between disease activity and anti-CADM-140/MDA5 titer measured by enzyme-linked immunosorbent assay (ELISA).

Methods

Sera from 63 patients with dermatomyositis (DM) [46 classic DM, 17 clinically amyopathic DM (CADM)] were screened for autoantibody using immunoprecipitation assay. Anti-CADM-140/MDA5-positive sera were examined for their titer by anti-CADM-140/MDA5 ELISA. Potential associations between anti-CADM-140/MDA5 titer and clinical course or outcome were analyzed.

Results

Sera from 14 patients with DM (2 classic DM, 12 CADM) had anti-CADM-140/MDA5. Of ten patients with DM and rapidly progressive interstitial lung disease (RP-ILD), the mean titer of anti-CADM-140/MDA5 before treatment was significantly lower in patients who responded to therapy and survived (responder group, n = 4) than in those who did not respond and died (nonresponder group, n = 6) (110.3 vs. 356.9, P = 0.019). In the responder group, the mean titer of anti-CADM-140/MDA5 significantly decreased down to below the cutoff level after treatment (n = 3, 113.4 vs. 1.6, P = 0.033), whereas that of the nonresponder group did not decrease sufficiently and sustained high level (n = 4, 372.5 vs. 198.4, P = 0.31).

Conclusions

These results emphasize the clinical importance of anti-CADM-140/MDA5 antibody levels to predict outcomes of RP-ILD as well as to monitor disease activity in patients with DM and RP-ILD.