Recovery of renal function in patients with lupus nephritis and reduced renal function: the beneficial effect of hydroxychloroquine.

BACKGROUND: Reduced renal function is associated with worse renal outcome in patients with lupus nephritis (LN). However, there is insufficient knowledge regarding renal function recovery in patients with LN with reduced baseline renal function. Therefore, the present study aimed to investigate renal function recovery and related factors in patients with reduced baseline renal function. METHODS: The present retrospective longitudinal cohort study included patients with LN and reduced renal function. Reduced renal function was defined as an estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m2. Recovery of renal function was determined by an eGFR of >60 mL/min/1.73 m2 at six months after baseline, and factors associated with it were evaluated using logistic regression analysis. RESULTS: We included 90 patients with LN, with a mean eGFR value of 37.2 ± 13.9 mL/min/1.73 m2. Forty-six (51.1%) patients recovered their renal function after six months. On multivariate analysis, hydroxychloroquine use (odds ratio (OR) = 3.891, 95% confidence interval (CI) 1.196-12.653, p = 0.024), prolonged LN (OR = 0.926, 95% CI 0.874-0.981, p = 0.009) and high-grade tubular atrophy (OR = 0.451, 95% CI 0.208-0.829, p = 0.013) were associated with renal function recovery. During follow up, 25 patients were on end-stage renal disease (ESRD). Kaplan-Meier analysis revealed that renal function recovery after six months and lower probability of ESRD are associated. CONCLUSIONS: In patients with LN and reduced renal function, renal function recovery at six months was associated with use of hydroxychloroquine and inversely related to longer duration of LN and higher grade of tubular atrophy.

Gender difference in the impact of coexisting diabetes mellitus on long-term clinical outcome in people with heart failure: a report from the Korean Heart Failure Registry.

AIM: Few data are available on the gender-related differences in the prognostic impact of diabetes in people with heart failure. This study was performed to investigate whether there is a gender difference in the association between diabetes and long-term clinical outcomes in people hospitalized for heart failure. METHODS: A total of 3162 people hospitalized with heart failure (aged 67.4 ± 14.1 years, 50.4% females) from the data set of the nationwide registry were analysed. The primary endpoint was a composite of all-cause mortality and heart failure readmission. RESULTS: People with diabetes (30.5% for males vs. 31.1% for females, P = 0.740) were older and had more unfavourable risk factors and laboratory findings than those without diabetes in both genders. During a median follow-up period of 549 days, there were 1418 cases of composite events (44.8%). In univariable analysis, the coexistence of diabetes was significantly associated with a higher incidence of composite events in both genders (P < 0.05 each for males and females). In multivariable analysis, the prognostic impact of diabetes on the development of composite events remained significant in females even after controlling for potential confounders (hazard ratio 1.43, 95% confidence intervals 1.12-1.84; P = 0.004). However, an independent association between diabetes and composite events was not seen in males in the same multivariable analysis (P > 0.05). CONCLUSIONS: In people with heart failure, the impact of diabetes on long-term mortality and heart failure readmission seems to be stronger in females than in males. More careful and intensive management is needed especially in females with heart failure and diabetes.

Impact of stringent response in proteinuria on long-term renal outcomes in proliferative lupus nephritis.

OBJECTIVES: Favourable long-term prognosis in proliferative lupus nephritis (LN) is associated with the achievement of complete renal response (CR), which is defined as a urine protein/creatinine ratio (UPCR) of < 0.5. However, it is unclear whether a more stringent cut-off for proteinuria (normal value of proteinuria; UPCR < 0.15) is better than CR. We aimed to evaluate the effect of stringent CR, defined as a UPCR of <0.15, on long-term renal outcomes in proliferative LN. METHODS: We included 87 patients with class III or IV LN who achieved CR at one year after induction therapy. Clinical and laboratory data were compared between the stringent and non-stringent CR groups. Logistic regression analysis was performed to identify factors associated with achievement of stringent CR. Cox analysis was performed to analyse the risk factors for renal flare and development of chronic kidney disease (CKD). RESULTS: The stringent and non-stringent CR groups included 58 and 29 patients, respectively. The two groups showed no significant baseline differences in terms of the clinical, laboratory and pathological classification. The sustained CR rates during five years were 91.3% and 50.0% (p = 0.014) in the stringent and non-stringent CR groups, respectively. In Cox analyses, the achievement of stringent CR was associated with a lower risk of five-year renal flare rate (hazard ratio (HR) = 0.161, 95% confidence interval (CI) 0.063-0.411, p < 0.01) and development of CKD (HR = 0.189, 95% CI 0.047-0.752, p = 0.018). Mycophenolate mofetil induction therapy was associated with achievement of stringent CR at a borderline level of significance (HR = 7.268, 95% CI 0.894-59.089, p = 0.064). CONCLUSION: Achievement of stringent CR predicted lower risk of renal flare and development of CKD in proliferative LN. These findings suggest that stringent CR is a valuable treatment target in proliferative LN.

Effect of docetaxel duration on clinical outcomes: exploratory analysis of CLEOPATRA, a phase III randomized controlled trial.

Background: Combination pertuzumab, trastuzumab, and docetaxel (D) is considered standard first-line treatment of human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. This post hoc, exploratory analysis of CLEOPATRA study data evaluated the clinical effects of D treatment duration within this regimen. The clinical benefits of pertuzumab and trastuzumab by different durations of D treatment were also evaluated. Patients and methods: Patients with HER2-positive metastatic breast cancer received trastuzumab and D plus pertuzumab or placebo. Clinical outcomes were analyzed by the number of D cycles that patients received (<6D, 6D, or >6D). Progression-free survival (PFS) and overall survival (OS) for each treatment arm within each D cycle group were estimated using the Kaplan-Meier approach. Time-dependent, multivariate Cox regression was applied to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for HER2-targeted therapy and D cycle groups. Results: Overall, 804 patients received <6D (n = 119), 6D (n = 210), or >6D (n = 475) cycles. After adjusting for pertuzumab benefits versus placebo (PFS HR = 0.61, 95% CI 0.51-0.74, P < 0.0001; OS HR = 0.60, 95% CI, 0.49-0.74, P < 0.0001), >6D versus 6D cycles was not associated with statistically significant improvements in PFS (HR = 0.80, 95% CI 0.63-1.01, P = 0.0640) or OS (HR = 0.88, 95% CI 0.69-1.12, P = 0.3073). Consistent improvements in PFS and OS were observed with pertuzumab versus placebo, irrespective of D duration. The HRs for PFS were 0.395, 0.615, and 0.633 for <6D, 6D, and >6D cycles, respectively (P < 0.05 for all D cycle groups). Corresponding HRs for OS were 0.577, 0.700, and 0.612, respectively (P < 0.05 for <6D and >6D). Conclusions: After accounting for pertuzumab benefits, more than six cycles of D treatment was not associated with significant improvements in either PFS or OS compared with six cycles. The addition of pertuzumab to trastuzumab improved clinical outcomes versus trastuzumab plus placebo, regardless of D treatment duration. ClinicalTrials.gov identifier: NCT00567190.

Incidence and management of diarrhea in patients with HER2-positive breast cancer treated with pertuzumab.

Background: Pertuzumab disrupts heterodimerization between human epidermal growth factor receptor 2 (HER2) and epidermal growth factor receptor (EGFR), HER3, and HER4. Thus, pertuzumab could result in adverse events similar to those observed with EGFR antagonists, such as diarrhea. We report the incidence and severity of diarrhea observed with pertuzumab in the CLEOPATRA, NeoSphere, and TRYPHAENA studies. Patients and methods: Patients (n = 1443) had metastatic [CLEOPATRA (n = 804)] or early-stage breast cancer [NeoSphere (n = 416) and TRYPHAENA (n = 223)]. The incidence and severity of diarrhea were analyzed by treatment received. The incidence of febrile neutropenia concurrent with diarrhea and the effect of pre-existing gastrointestinal comorbidities were also evaluated. Subgroup analyses were carried out using CLEOPATRA data. Results: The incidence of all-grade diarrhea across studies was generally greater for pertuzumab-based treatment, ranging from 28% to 72% (grade 1, 21%-54%; grade 2, 8%-37%; grade 3, 0%-12%; grade 4, 0%). Incidence was highest during the first pertuzumab-containing cycle, decreasing with subsequent cycles. Dose delays or discontinuations due to diarrhea were infrequent, ranging from 0% to 8%. Among pertuzumab-treated patients with diarrhea, 47%-67% received pharmacological intervention, most commonly with loperamide. Overlap between diarrhea and febrile neutropenia was uncommon, ranging from 0% to 11%. No relationship was observed between pre-existing gastrointestinal comorbidities and diarrhea. In CLEOPATRA, patients ≥65 years treated with pertuzumab had a higher incidence of grade 3 diarrhea than patients <65 years (19% versus 8%). All-grade diarrhea occurred at greater frequency among pertuzumab-treated Asian versus white patients with metastatic breast cancer (74% versus 63%); the corresponding rates in the control arm were 53% and 45%, respectively. Conclusions: In both the metastatic and early-stage breast cancer settings, diarrhea was common but manageable for all pertuzumab-containing regimens. Diarrheal episodes were mainly low grade and occurred most often during the first treatment cycle. Diarrheal-related drug delays or discontinuations were uncommon. ClinicalTrials.gov identifiers: NCT00567190 (CLEOPATRA), NCT00545688 (NeoSphere), NCT00976989 (TRYPHAENA).

Influence of hepatitis B virus reactivation on the recurrence of HBV-related hepatocellular carcinoma after curative resection in patients with low viral load.

It is unclear whether the reactivation of hepatitis B virus (HBV) influences the prognosis of hepatocellular carcinoma (HCC) after resection in patients with chronic hepatitis B. The aim of this study was to identify the influence of HBV reactivation on the recurrence of hepatitis B-related HCC after curative resection in patients with low viral load (HBV DNA <2000 IU/mL). We retrospectively analysed a total of 130 patients who underwent curative resection for HBV-related early stage HCC (single nodule; <5 cm/two or three nodules; <3 cm) with pre-operative HBV DNA levels <2000 IU/mL with serial HBV DNA tests. The predictive factors including HBV reactivation for the recurrence of HBV-related HCC after curative resection were investigated. Fifty-three patients (41%) had HBV reactivation after resection among 130 patients. HBV reactivation was observed in 22 of 53 patients with undetectable baseline HBV DNA and in 31 of 77 patients with detectable baseline HBV DNA. Cumulative recurrence rates after resection at 1, 2 and 3 years were 17.0%, 23.3% and 31.4%, respectively. The multivariable analysis demonstrated that the risk factors for the recurrence were the presence of microvascular invasion (hazard ratio (HR) 2.62, P = 0.003), multinodularity (HR 4.61, P = 0.005), HBV reactivation after resection (HR 2.03, P = 0.032) and HBeAg positivity (HR 2.06, P = 0.044). HBV reactivation after curative resection is associated with the recurrence of HBV-related HCC in patients with low viral load.

Lupus enteritis: clinical characteristics and predictive factors for recurrence.

OBJECTIVES: To compare the clinical characteristics of lupus enteritis (LE) and non-enteric lupus (non-LE) patients and identify predictors of LE recurrence. METHODS: We retrospectively reviewed the medical records of 62 systemic lupus erythematosus (SLE) patients in a tertiary hospital who experienced enteric symptoms and underwent abdominal computed tomography scanning between January 1997 and December 2013. We compared the clinical characteristics between LE and non-LE patients and between recurrent LE and non-recurrent LE cases. RESULTS: Out of 62 SLE patients with enteric symptoms, 46 cases (74%) were compatible with LE based on computed tomography findings. The C4 level was decreased in the LE group compared with the non-LE group (9.0 ± 5.6 vs. 12.3 ± 6.2, p = 0.032). Recurrence of LE was observed in 14 patients (28%). Initial involvement at the colon (79% vs. 41%, p = 0.026) and bladder with/without the ureter was more common in the recurrent group (57% vs. 25%, p = 0.048). By multivariate analysis, the hazard ratios of variables associated with recurrence were 4.689 for colon involvement (95% confidence interval: 1.245-17.659, p = 0.0220] and 5.468 for cystitis with/without ureteritis (95% confidence interval: 1.629-18.360, p = 0.006). CONCLUSION: Colon and urinary tract involvement in LE patients may be associated with the recurrence of LE.

Long-term survivor characteristics in HER2-positive metastatic breast cancer from registHER.

BACKGROUND: Data characterising long-term survivors (LTS) with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) are limited. This analysis describes LTS using registHER observational study data. METHODS: A latent class modelling (LCM) approach was used to identify distinct homogenous patient groups (or classes) based on progression-free survival (PFS), overall survival, and complete response. Demographics, clinicopathologic factors, first-line treatment patterns, and clinical outcomes were described for each class. Class-associated factors were evaluated using logistic regression analysis. RESULTS: LCM identified two survivor groups labelled as LTS (n=244) and short-term survivors (STS; n=757). Baseline characteristics were similar between groups, although LTS were more likely to be white (83.6% vs 77.8%) with oestrogen receptor-positive (ER+) or progesterone receptor-positive (PgR+) disease (59.4% vs 50.9%). Median PFS in LTS was 37.2 (95% confidence interval (CI): 32.9-40.5) vs 7.3 months (95% CI: 6.8-8.0) in STS. Factors associated with long-term survival included ER+ or PgR+ disease, metastasis to node/local sites, first-line trastuzumab use, and first-line taxane use. CONCLUSIONS: Prognostic variables identified by LCM define a HER2-positive MBC patient profile and therapies that may be associated with more favourable long-term outcomes, enabling treatment selection appropriate to the patient's disease characteristics.

Rheological and tribological properties of native potato starch agglomerated by fluidized bed granulator.

We explored the rheological and tribological properties of potato starch agglomerated with a sugar binder (maltodextrin or lactose) at various concentrations by using a fluidized bed granulator. The magnitudes of consistency index and apparent viscosity of agglomerated potato starch (APS) decreased as the binder concentration was increased. Moreover, APS with a sugar binder showed lower viscoelastic moduli and higher tan δ values compared to APS with water as the binder (the control). The gel strength of all agglomerates decreased as the sugar concentration was increased. All samples showed anti-thixotropic behavior, and especially, APS with 20 % lactose showed a small anti-thixotropic area. Utilizing the Arrhenius equation clearly elucidated the effect of temperature on the apparent viscosity of all the samples. Although the maltodextrin concentration had little influence on the activation energy of APS, it increased as the lactose concentration was increased. APS samples with a sugar binder showed greater friction coefficient values compared to the control, with maltodextrin having a significant impact. The findings indicate that the rheological and tribological properties of APS rely on the type and concentration of sugar binder.

Automated Assessment of the DWI-FLAIR Mismatch in Patients with Acute Ischemic Stroke: Added Value to Routine Clinical Practice.

BACKGROUND AND PURPOSE: The DWI-FLAIR mismatch is used to determine thrombolytic eligibility in patients with acute ischemic stroke when the time since stroke onset is unknown. Commercial software packages have been developed for automated DWI-FLAIR classification. We aimed to use e-Stroke software for automated classification of the DWI-FLAIR mismatch in a cohort of patients with acute ischemic stroke and in a comparative analysis with 2 expert neuroradiologists. MATERIALS AND METHODS: In this retrospective study, patients with acute ischemic stroke who had MR imaging and known time since stroke onset were included. The DWI-FLAIR mismatch was evaluated by 2 neuroradiologists blinded to the time since stroke onset and automatically by the e-Stroke software. After 4 weeks, the neuroradiologists re-evaluated the MR images, this time equipped with automated predicted e-Stroke results as a computer-assisted tool. Diagnostic performances of e-Stroke software and the neuroradiologists were evaluated for prediction of DWI-FLAIR mismatch status. RESULTS: A total of 157 patients met the inclusion criteria. A total of 82 patients (52%) had a time since stroke onset of ≤4.5 hours. By means of consensus reads, 81 patients (51.5%) had a DWI-FLAIR mismatch. The diagnostic accuracy (area under the curve/sensitivity/specificity) of e-Stroke software for the determination of the DWI-FLAIR mismatch was 0.72/90.0/53.9. The diagnostic accuracy (area under the curve/sensitivity/specificity) for neuroradiologists 1 and 2 was 0.76/69.1/84.2 and 0.82/91.4/73.7, respectively; both significantly (P < .05) improved to 0.83/79.0/86.8 and 0.89/92.6/85.5, respectively, following the use of e-Stroke predictions as a computer-assisted tool. The interrater agreement (κ) for determination of DWI-FLAIR status was improved from 0.49 to 0.57 following the use of the computer-assisted tool. CONCLUSIONS: This automated quantitative approach for DWI-FLAIR mismatch provides results comparable with those of human experts and can improve the diagnostic accuracies of expert neuroradiologists in the determination of DWI-FLAIR status.

Re-categorisation of male lower urinary tract symptoms based on the international prostate symptom score questionnaire.

AIMS: The purpose of this study was to develop a new sub-classification system for male lower urinary tract symptoms (LUTS)-mild, moderate and severe-using the conventional International Prostate Symptoms Score (I-PSS). METHODS: From October 2007 to March 2012, a total of 2234 male patients (≥ 50 years old) presenting with LUTS were enrolled in this study. Patients were sorted according to their I-PSS (ranging from 1 to 35 points) and divided into three groups based on their quality of life (QoL) score. A chi-square automatic interaction detection (CHAID) algorithm, based on adjusted significance testing, was used. The Kappa coefficient was calculated for the agreement of original and new categorisation. RESULTS: Mean total I-PSS and QoL scores were 11.0 and 2.9 respectively. According to the original classification, 838 patients (38.6%) had mild, 1053 (48.5%) had moderate and 282 (13.0%) had severe symptoms. After the CHAID algorithm was applied, the scores were re-categorised as 'mild' (1-6 points), 'moderate' (7-21 points) and 'severe' (22-35 points). The overall model was able to correctly predict whether an I-PSS was associated with mild, moderate or severe symptoms, with 70.1% accuracy. According to this new classification, 704 patients (32.4%) were shown to have mild, 1255 (57.8%) to have moderate and 214 (9.8%) to have severe LUTS. The agreement of conventional and new categorisation is very strong (Kappa coefficient = 0.84). CONCLUSIONS: Conventional categorisation of LUTS by I-PSS needs to be updated and the category of moderate LUTS should be broadened.

Effect of micro-osteoperforations on the rate of tooth movement.

INTRODUCTION: Our objectives were to study the effect of micro-osteoperforations on the rate of tooth movement and the expression of inflammatory markers. METHODS: Twenty adults with Class II Division 1 malocclusion were divided into control and experimental groups. The control group did not receive micro-osteoperforations, and the experimental group received micro-osteoperforations on 1 side of the maxilla. Both maxillary canines were retracted, and movement was measured after 28 days. The activity of inflammatory markers was measured in gingival crevicular fluid using an antibody-based protein assay. Pain and discomfort were monitored with a numeric rating scale. RESULTS: Micro-osteoperforations significantly increased the rate of tooth movement by 2.3-fold; this was accompanied by a significant increase in the levels of inflammatory markers. The patients did not report significant pain or discomfort during or after the procedure, or any other complications. CONCLUSIONS: Micro-osteoperforation is an effective, comfortable, and safe procedure to accelerate tooth movement and significantly reduce the duration of orthodontic treatment.

Rheological characteristics of concentrated ternary gum mixtures with xanthan gum, guar gum, and carboxymethyl cellulose: Effect of NaCl, sucrose, pH, and temperature.

Our goal was to investigate the effects of various conditions of media (NaCl, sucrose, pH, and temperature) on the steady and dynamic shear rheological properties of a concentrated ternary gum mixture system (1.0 wt%) containing xanthan gum (XG), guar gum (GG), and carboxymethyl cellulose (CMC). Regardless of the media conditions, all gum mixtures exhibited a high shear-thinning behavior with a low flow behavior index (<0.30). NaCl addition resulted in a decrease in the consistency index (K, 32.8-16.1 Pa·sn) and apparent viscosity at 50 s-1 (ηa,50, 1.00-0.75 Pa·s), as well as the elastic modulus (G') and viscous modulus (G″) due to the charge screening effect. Similar result was observed with an increase in acidity of media. The presence of sucrose also induced the decrease in the ηa,50, K, G', and G″ values of the ternary gum, but tan δ (G″/G') decreased, indicative of higher weak gel-like properties. No effect of NaCl or sucrose addition on the temperature dependence of G' values was observed, whereas pH adjustment was impacted. These results demonstrated that the presence of co-solute, the acidity of media, and temperature influenced the rheological properties of ternary gum, and in particular acid condition gave a great impact.

Case series of sural island flaps used for soft-tissue defects of the distal-third lower extremity.

OBJECTIVE: To establish the sural island fasciocutaneous flap as an initial consideration for distal third lower-extremity soft tissue coverage and to provide non-plastic surgeons with a procedure they can perform on their own. METHOD: Literature on reverse sural island fasciocutaneous flaps was reviewed and summarised. We then assessed our care series of sural island flaps from 2008-2011 and looked to provide our operative technique and patient outcomes. RESULTS: Nine patients, aged 12-70 years old, with greater than 1 year follow-up, were reviewed. Five patients had diabetes, peripheral vascular disease, or smoked tobacco. All patients healed their soft tissue coverage with minimal complication and were able to accommodate normal footwear. CONCLUSION: Reverse sural island flaps are resilient flaps that should be considered as an alternative to free muscle transfer, for distal third lower extremity coverage. DECLARATION OF INTEREST: There were no external sources of funding for this study. The authors have no conflicts of interest to declare.

Factors associated with acute gout attacks in normouricaemic gout patients receiving allopurinol: a retrospective study.

OBJECTIVE: To identify factors associated with acute gout attacks in normouricaemic gout patients receiving allopurinol. METHODS: We reviewed the medical records of 860 patients with chronic gout who were treated with allopurinol at a single tertiary hospital between 2003 and 2009. Of these, 135 patients had serum urate concentrations ≤ 360 µmol/L (6 mg/dL). Patients whose serum urate concentrations exceeded 360 µmol/L (6 mg/dL) at least once during follow-up were excluded. Patients who experienced at least one acute attack during follow-up, despite normouricaemia [≤ 360 µmol/L (6 mg/dL)], were classified as the Attack group (n = 51). The others were classified as the Non-attack group (n = 84). RESULTS: The gout disease duration was significantly longer in the Attack group than in the Non-attack group (p = 0.036). The presence of tophi and multiple joint involvement were associated with acute attacks in normouricaemic gout patients. Multivariate analysis showed that both the presence of tophi [odds ratio (OR) 4.16, 95% confidence interval (CI) 1.41-12.23, p = 0.010] and the number of involved joints (OR 1.51, 95% CI 1.05-2.17, p = 0.028) were independently associated with acute attacks in normouricaemic gout patients receiving allopurinol. CONCLUSION: The presence of tophi and multiple joint involvement were associated with acute attacks in normouricaemic gout patients receiving allopurinol.