- Randomized phase 2 trial of pemetrexed, pemetrexed/bevacizumab, and pemetrexed/carboplatin/bevacizumab in patients with stage IIIB/IV non-small cell lung cancer and an Eastern Cooperative Oncology Group performance status of 2. [Journal Article]
- CCancer 2018 Feb 16
- CONCLUSIONS: All 3 regimens were feasible for patients with advanced NSCLC and an ECOG performance status of 2. The addition of bevacizumab to pemetrexed increased the overall response rate. The efficacy of pemetrexed/carboplatin/bevacizumab (median PFS, 4.8 months) approached the prespecified study PFS goal of 5 months. Larger studies will be necessary to define the role of bevacizumab in addition to standard pemetrexed and carboplatin in this population. Cancer 2018. © 2018 American Cancer Society.
- Severe tricuspid regurgitation and seizure on postpartum day 10: case report of late postpartum eclampsia. [Journal Article]
- ACActa Clin Belg 2018 Feb 16; :1-4
- CONCLUSIONS: This caseemphasizes the importance of considering late postpartum eclampsia in patients presenting with signs of pulmonary edema even several days after delivery, as early diagnosis and prompt initiation of appropriate antihypertensive and anticonvulsant therapy can prevent severe complications.
- Improving monitoring of diabetic complications in home care patients. [Journal Article]
- BOBMJ Open Qual 2017; 6(2):e000053
- CONCLUSIONS: In conclusion, quality improvement methods were successfully used to improve monitoring of diabetes complications according to international guidelines in a very vulnerable population.
- HDAC6 Inhibition Promotes Transcription Factor EB Activation and Is Protective in Experimental Kidney Disease. [Journal Article]
- FPFront Pharmacol 2018; 9:34
- To contend with the deleterious effects of accumulating misfolded protein aggregates or damaged organelles cells rely on a system of quality control processes, among them the autophagy-lysosome pathw...
To contend with the deleterious effects of accumulating misfolded protein aggregates or damaged organelles cells rely on a system of quality control processes, among them the autophagy-lysosome pathway. This pathway is itself controlled by a master regulator transcription factor termed transcription factor EB (TFEB). When TFEB localizes to the cell nucleus it promotes the expression of a number of genes involved in protein clearance. Here, we set out to determine (1) whether TFEB expression is altered in chronic kidney disease (CKD); (2) whether inhibition of the cytosolic deacetylase histone deacetylase 6 (HDAC6) affects TFEB acetylation and nuclear localization; and (3) whether HDAC6 inhibition, in turn, alters the natural history of experimental CKD. TFEB mRNA and protein levels were observed to be diminished in the kidneys of humans with diabetic kidney disease, accompanied by accumulation of the protein aggregate adaptor protein p62 in tubule epithelial cells. In cultured NRK-52E cells, HDAC6 inhibition with the small molecule inhibitor Tubastatin A acetylated TFEB, increasing TFEB localization to the nucleus and attenuating cell death. In a rat model of CKD, Tubastatin A prevented the accumulation of misfolded protein aggregates in tubule epithelial cells, attenuated proteinuria progression, limited tubule cell death and diminished tubulointerstitial collagenous matrix deposition. These findings point to the common occurrence of dysregulated quality control processes in CKD and they suggest that TFEB downregulation may contribute to tubule injury in CKD. They also identify a regulatory relationship between HDAC6 and TFEB. HDAC6 inhibitors and TFEB activators both warrant further investigation as treatments for CKD.
- Early Renin-angiotensin System Blockade Improved Short-term and Longterm Renal Outcomes in Systemic Lupus Erythematosus Patients with Antiphospholipid-associated Nephropathy. [Journal Article]
- JRJ Rheumatol 2018 Feb 15
- CONCLUSIONS: Early RAAS blockade improved the short-term and longterm renal outcomes in SLE patients with aPLN. The renal protective effect of RASI was independent of its antihypertensive and antiproteinuric effects.
- Multitarget therapy of mycophenolate mofetil and cyclosporine A for induction treatment of refractory lupus nephritis. [Journal Article]
- LLupus 2018 Jan 01; :961203318758508
- Standard induction therapy for lupus nephritis (LN) with mycophenolate mofetil (MMF) or cyclophosphamide (CYC) is often ineffective. Evidence on rescue induction regimens is scarce. We analyzed effic...
Standard induction therapy for lupus nephritis (LN) with mycophenolate mofetil (MMF) or cyclophosphamide (CYC) is often ineffective. Evidence on rescue induction regimens is scarce. We analyzed efficacy and tolerability of multitarget immunosuppression with MMF and cyclosporine A (CsA) as induction treatment for LN (class III/IV/V) refractory to CYC and/or MMF. We included all six refractory LN patients (class IV = 3, class V = 2, class III = 1) from our 400-patient tertiary Lupus Clinic observed between 2012 and 2015. Four patients had previously received pulse CYC. All six received MMF as first or second induction therapy and CsA was added once failure to reach remission was established. Daily dose of MMF was 2-3 g and CsA was dosed up to 2.6-3.7 mg/kg/day. Mean proteinuria was reduced from 2407 mg/24 hours at the start of the MMF+CsA regimen to 544 mg/day after six months. The mean prednisolone dose was reduced from 17.5 to 6 mg/day after six months of MMF+CsA. Four patients achieved a complete renal response, one patient had a partial renal response and one failed to respond. None of the patients presented with adverse events. These data suggest that adding CsA to MMF can induce complete remission of refractory LN and is well tolerated.
- Outcomes of multitarget therapy using mycophenolate mofetil and tacrolimus for refractory or relapsing lupus nephritis. [Journal Article]
- LLupus 2018 Jan 01; :961203318758505
- Objectives Outcomes of systemic lupus erythematosus (SLE) have significantly improved over the years. However, when there is major organ involvement, the outcomes can still be unfavorable. Outcomes o...
Objectives Outcomes of systemic lupus erythematosus (SLE) have significantly improved over the years. However, when there is major organ involvement, the outcomes can still be unfavorable. Outcomes of multitarget therapy using mycophenolate mofetil (MMF) and tacrolimus in patients with SLE who were refractory to standard therapy were assessed. Methods We retrospectively reviewed the Hanyang BAE lupus cohort to identify patients with biopsy-confirmed lupus nephritis (classes III, IV, or V) who failed to either achieve complete response with standard induction therapy or those who had a lupus flare after achieving a complete response with conventional induction therapy and subsequently were switched to multitarget combination therapy with MMF and tacrolimus. Outcomes, including renal response, proteinuria, glomerular filtration rate, serum albumin, anti-dsDNA antibody level, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), and complements, were assessed at six and 12 months. Results Twenty-nine patients, including 12 who failed to achieve a complete response at 12 months after initial conventional induction therapy and 17 with lupus flare after achieving a complete response at 12 months and treated with multitarget therapy, were included in the analysis. At six months, 53.9% of the patients showed a response, with 15.4% of patients showing a complete response and 38.5% of patients showing a partial response. At 12 months, 55.5% of patients exhibited a response (with complete and partial response in 25.9% and 29.6%, respectively). The dosage of steroids was significantly decreased at six months compared with baseline and was maintained at 12 months. Proteinuria, anti-double-stranded DNA antibody positivity, as well as C3 and C4 levels improved after treatment and persisted until 12 months, but were not significant. SLEDAI also improved. Outcomes were significantly better in patients who had a complete response but later had a flare, resulting in the use of multitarget therapy and achieving a subsequent complete response. Conclusions Multitarget therapy with MMF and tacrolimus can be a reasonable option in refractory lupus nephritis patients who failed to show adequate response to conventional induction therapy or who had flares during maintenance therapy. This treatment can help patients achieve a renal response and reduce the use of steroids.
- Stroke volume and proteinuria in obesity-related glomerulopathy: potential role in pathogenesis and choice of antihypertensive regimen. [Letter]
- JCJ Clin Hypertens (Greenwich) 2018 Feb 15
- Hypertension in a resource-limited setting: Is it associated with end organ damage in older adults in rural Tanzania? [Journal Article]
- JCJ Clin Hypertens (Greenwich) 2018 Feb 15
- Few data from sub-Saharan Africa exist on the effects of hypertension on the organs of the human body. We aimed to establish the prevalence of hypertensive end organ damage (EOD) in an elderly cohort...
Few data from sub-Saharan Africa exist on the effects of hypertension on the organs of the human body. We aimed to establish the prevalence of hypertensive end organ damage (EOD) in an elderly cohort of Tanzanians. The population aged 70 years and over of 2 villages in northern Tanzania (n = 246), had blood pressure (BP) data available from 2010 and 2013, and underwent in-depth follow-up for markers of hypertensive EOD in 2016. Assessment included ankle-brachial pressure index, lying-standing BP, electrocardiogram, and mid-stream urine dip. Sustained hypertension (those with hypertension at all 3 assessments) was found in 129 (52.4% subjects). Of the entire cohort, 13.9% had left ventricular hypertrophy and 26.4% had peripheral arterial disease, both of which were associated with sustained hypertension, although orthostatic hypotension, stroke, proteinuria, and arterial stiffening were not. Further investigation, particularly in younger age groups, is merited if hypertension-associated morbidity is to be controlled.
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- Non-invasive assessment of kidney allograft fibrosis with shear wave elastography: A radiological-pathological correlation analysis. [Journal Article]
- IJInt J Urol 2018 Feb 14
- CONCLUSIONS: Shear wave elastography can be used as a non-invasive tool to evaluate kidney allograft fibrosis with reasonable interobserver agreement and superior test performance to serum creatinine in detecting early tubulointerstitial fibrosis.