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Cut-off value of strut-vessel distance for the resolution of acute incomplete stent apposition in the early phase using serial optical coherence tomography after cobalt-chromium everolimus-eluting stent implantation.
Oda, H, Itoh, T, Sasaki, W, Uchimura, Y, Taguchi, Y, Kaneko, K, Sakamoto, T, Goto, I, Sakuma, M, Ishida, M, et al
Journal of cardiology. 2020;(6):641-647
Abstract
OBJECTIVE The purpose of this study was to identify a cut-off value to predict the resolution of incomplete-stent-apposition (ISA) after cobalt-chromium everolimus-eluting stent (CoCr-EES) implantation at early follow-up. BACKGROUND To date, appropriate stent apposition at the acute period using intracoronary imaging has been recommended because persistent ISA is considered to be a risk factor for stent thrombosis. We examined the indices for resolving acute ISA. In particular, we determined the cut-off value for strut vessel distance (SV-distance) as visualized by optical coherence tomography (OCT) at 8 months after CoCr-EES implantation. However, the cut-off value of SV-distance for the earlier resolution of ISA is unclear. METHODS A total of 95 cases and 103 stents were registered in the MECHANISM Elective substudy. The SV-distance was measured at the deepest site of the target malapposition and every 1 mm from the proximal edge to the distal edge of the mal-apposed area using OCT. Cut-off values for ISA resolution at 1 and 3 months were estimated by SV-distance using receiver operating characteristic analysis. RESULTS The total number of analyzed struts was 14,418 at the 1-month follow-up and 11,986 at the 3-month follow-up. The optimal SV-distance cut-off values just after stent implantation to predict ISA resolution were 185 µm at the 1-month follow-up and 195 μm at the 3-month follow-up. CONCLUSION For resolution of ISA, SV-distance cut-off values of 185 µm at 1 month postimplantation and 195 μm at 3 months postimplantation can be used as the index of endpoint of the percutaneous coronary intervention.
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Drug Exposure in Newborns: Effect of Selected Drugs Prescribed to Mothers During Pregnancy and Lactation.
Rentsch, KM
Therapeutic drug monitoring. 2020;(2):255-263
Abstract
The number of newborns exposed to therapeutic drugs during pregnancy is growing because of the increased use of drugs during pregnancy. In recent years, advances in our understanding of drug placental transfer have augmented the likelihood of a healthy baby in mothers with chronic diseases needing drug therapy. Globally, for example, more than 1.4 million pregnancies in 2015 have been burdened with antiretroviral drugs due to an increasing number of HIV-positive women treated with these drugs, particularly in low- and middle-income countries. In most cases, the fetus is exposed to much higher drug doses in utero than the newborn nursed by the mother. Drug transfer through the placenta takes place by passive diffusion, active transport, or facilitated transport, and drug concentrations in the fetal circulation may be comparable to that in the mother's blood concentration. The excretion of drugs into breastmilk predominantly occurs by passive diffusion, allowing only the non-protein-bound fraction of the blood drug concentration to penetrate. Drug agencies in the United States and Europe highly recommend performing clinical trials in pregnant or breastfeeding women. However, only a few drugs have reported statistically sound data in these patient groups. Most available results concerning pregnancy are obtained from observational studies after birth, assessing outcomes in the newborn or by measuring drug concentrations in the mother and umbilical cord blood. In the case of the lactation period, some studies have evaluated drug concentrations in breastmilk and blood of the mother and/or infant. In this review, exposure to antiretrovirals, immunosuppressants used after solid organ transplantation, and antiepileptics during pregnancy and lactation has been discussed in detail.
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Serum magnesium, hepatocyte nuclear factor 1β genotype and post-transplant diabetes mellitus: a prospective study.
van der Burgh, AC, Moes, A, Kieboom, BCT, van Gelder, T, Zietse, R, van Schaik, RHN, Hesselink, DA, Hoorn, EJ
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2020;(1):176-183
Abstract
BACKGROUND Retrospective studies suggest that tacrolimus-induced hypomagnesaemia is a risk factor for post-transplant diabetes mellitus (PTDM), but prospective studies are lacking. METHODS This was a prospective study with measurements of serum magnesium and tacrolimus at pre-specified time points in the first year after living donor kidney transplantation (KT). The role of single nucleotide polymorphisms (SNPs) in hepatocyte nuclear factor 1β (HNF1β) was also explored because HNF1β regulates insulin secretion and renal magnesium handling. Repeated measurement and regression analyses were used to analyse associations with PTDM. RESULTS In our cohort, 29 out of 167 kidney transplant recipients developed PTDM after 1 year (17%). Higher tacrolimus concentrations were significantly associated with lower serum magnesium and increased risk of hypomagnesaemia. Patients who developed PTDM had a significantly lower serum magnesium trajectory than patients who did not develop PTDM. In multivariate analysis, lower serum magnesium, age and body mass index were independent risk factors for PTDM. In recipients, the HNF1β SNP rs752010 G > A significantly increased the risk of PTDM [odds ratio (OR) = 2.56, 95% confidence interval (CI) 1.05-6.23] but not of hypomagnesaemia. This association lost significance after correction for age and sex (OR = 2.24, 95% CI 0.90-5.57). No association between HNF1β SNPs and PTDM was found in corresponding donors. CONCLUSIONS A lower serum magnesium in the first year after KT is an independent risk factor for PTDM. The HNF1β SNP rs752010 G > A may add to this risk through an effect on insulin secretion rather than hypomagnesaemia, but its role requires further confirmation.
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Impact of a Mobile Health Intervention on Long-term Nonadherence After Lung Transplantation: Follow-up After a Randomized Controlled Trial.
Geramita, EM, DeVito Dabbs, AJ, DiMartini, AF, Pilewski, JM, Switzer, GE, Posluszny, DM, Myaskovsky, L, Dew, MA
Transplantation. 2020;(3):640-651
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Abstract
BACKGROUND In a randomized controlled trial, lung transplant recipients (LTRs) using a mobile health intervention, Pocket Personal Assistant for Tracking Health (Pocket PATH), showed better adherence to the medical regimen than LTRs receiving usual care during the first year posttransplant. We examined whether these effects were maintained beyond the end of the trial and evaluated other potential risk factors for long-term nonadherence. METHODS Adherence in 8 areas was evaluated at follow-up in separate LTR and family caregiver (collateral) assessments. Pocket PATH and usual care groups' nonadherence rates were compared; multivariable regression analyses then examined and controlled for other patient characteristics' associations with nonadherence. RESULTS One hundred five LTRs (75% of survivors) were assessed (M = 3.9 years posttransplant, SD = 0.8). Nonadherence rates in the past month were 23%-81% for self-care and lifestyle requirements (diet, exercise, blood pressure monitoring, spirometry), 13%-23% for immunosuppressants and other medications, and 4% for tobacco use, with 31% clinic appointment nonadherence in the past year. In multivariable analysis, the Pocket PATH group showed lower risk of nonadherence to lifestyle requirements (diet/exercise) than the usual care group (P < 0.05). Younger age and factors during the first year posttransplant (acute graft rejection, chronically elevated anxiety, less time rehospitalized, nonadherence at the final randomized controlled trial assessment) were each associated with nonadherence in at least 1 area at follow-up (P < 0.05). CONCLUSIONS Pocket PATH did not have sustained impact on most areas of the regimen, although we identified other risk factors for long-term nonadherence. Future work should explore strategies to facilitate sustained effects of mobile health interventions.
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Application of PLGA nano/microparticle delivery systems for immunomodulation and prevention of allotransplant rejection.
Keshavarz Shahbaz, S, Foroughi, F, Soltaninezhad, E, Jamialahmadi, T, Penson, PE, Sahebkar, A
Expert opinion on drug delivery. 2020;(6):767-780
Abstract
INTRODUCTION Allograft transplantation is an effective end-point therapy to replace the function of an impaired organ. The main problem associated with allotransplantation is the induction of immune responses that results in acute and chronic graft rejection. To modulate the response of the immune system, transplant recipients generally take high dose immunosuppressant drugs for life. These drugs are associated with serious side effects such as infection with opportunistic pathogens and the development of neoplasia. AREAS COVERED We reviewed the obstacles to successful transplantation and PLGA-based strategies to reduce immune-mediated allograft rejection. EXPERT OPINION Biomaterial-based approaches using micro- and nanoparticles such as poly (lactic-co-glycolic acid) (PLGA) can be used to achieve controlled release of drugs. This approach decreases the required effective dose of drugs and enables local delivery of these agents to specific tissues and cells, whilst decreasing systemic effects.
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Effect of belimumab on proteinuria and anti-phospholipase A2 receptor autoantibody in primary membranous nephropathy.
Barrett, C, Willcocks, LC, Jones, RB, Tarzi, RM, Henderson, RB, Cai, G, Gisbert, SI, Belson, AS, Savage, CO
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2020;(4):599-606
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BACKGROUND Immunosuppressant drugs reduce proteinuria and anti-phospholipase A2 receptor autoantibodies (PLA2R-Ab) in primary membranous nephropathy (PMN) with varying success and associated toxicities. This study aimed to evaluate the effect of belimumab on proteinuria and PLA2R-Ab in participants with PMN. METHODS In this prospective, open-label, experimental medicine study, 14 participants with PMN and persistent nephrotic-range proteinuria received up to 2 years belimumab monotherapy (10 mg/kg, every 4 weeks). Changes in proteinuria (urinary protein:creatinine ratio), PLA2R-Ab, albumin, cholesterol, B-cell subsets and pharmacokinetics were analysed during treatment and up to 6 months after treatment. RESULTS Eleven participants completed to the primary endpoint (Week 28) and nine participants completed the study. In the intention-to-treat population population, baseline proteinuria of 724 mg/mmol [95% confidence interval (CI) 579-906] decreased to 498 mg/mmol (95% CI 383-649) and 130 mg/mmol (95% CI 54-312) at Weeks 28 and 104, respectively, with changes statistically significant from Week 36 (n = 11, P = 0.047). PLA2R-Ab decreased from 174 RU/mL (95% CI 79-384) at baseline to 46 RU/mL (95% CI 16-132) and 4 RU/mL (95% CI 2-6) at Weeks 28 and 104, respectively, becoming statistically significant by Week 12 (n = 13, P = 0.02). Nine participants achieved partial (n = 8) or complete (n = 1) remission. Participants with abnormal albumin and/or cholesterol at baseline gained normal/near normal levels by the last follow-up. Adverse events were consistent with those expected in this population. CONCLUSIONS Belimumab treatment in participants with PMN can reduce PLA2R-Ab and subsequently proteinuria, important preludes to remission induction.
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IPNA clinical practice recommendations for the diagnosis and management of children with steroid-resistant nephrotic syndrome.
Trautmann, A, Vivarelli, M, Samuel, S, Gipson, D, Sinha, A, Schaefer, F, Hui, NK, Boyer, O, Saleem, MA, Feltran, L, et al
Pediatric nephrology (Berlin, Germany). 2020;(8):1529-1561
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Abstract
Idiopathic nephrotic syndrome newly affects 1-3 per 100,000 children per year. Approximately 85% of cases show complete remission of proteinuria following glucocorticoid treatment. Patients who do not achieve complete remission within 4-6 weeks of glucocorticoid treatment have steroid-resistant nephrotic syndrome (SRNS). In 10-30% of steroid-resistant patients, mutations in podocyte-associated genes can be detected, whereas an undefined circulating factor of immune origin is assumed in the remaining ones. Diagnosis and management of SRNS is a great challenge due to its heterogeneous etiology, frequent lack of remission by further immunosuppressive treatment, and severe complications including the development of end-stage kidney disease and recurrence after renal transplantation. A team of experts including pediatric nephrologists and renal geneticists from the International Pediatric Nephrology Association (IPNA), a renal pathologist, and an adult nephrologist have now developed comprehensive clinical practice recommendations on the diagnosis and management of SRNS in children. The team performed a systematic literature review on 9 clinically relevant PICO (Patient or Population covered, Intervention, Comparator, Outcome) questions, formulated recommendations and formally graded them at a consensus meeting, with input from patient representatives and a dietician acting as external advisors and a voting panel of pediatric nephrologists. Research recommendations are also given.
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Targeting immunometabolism as an anti-inflammatory strategy.
Pålsson-McDermott, EM, O'Neill, LAJ
Cell research. 2020;(4):300-314
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The growing field of immunometabolism has taught us how metabolic cellular reactions and processes not only provide a means to generate ATP and biosynthetic precursors, but are also a way of controlling immunity and inflammation. Metabolic reprogramming of immune cells is essential for both inflammatory as well as anti-inflammatory responses. Four anti-inflammatory therapies, DMF, Metformin, Methotrexate and Rapamycin all work by affecting metabolism and/or regulating or mimicking endogenous metabolites with anti-inflammatory effects. Evidence is emerging for the targeting of specific metabolic events as a strategy to limit inflammation in different contexts. Here we discuss these recent developments and speculate on the prospect of targeting immunometabolism in the effort to develop novel anti-inflammatory therapeutics. As accumulating evidence for roles of an intricate and elaborate network of metabolic processes, including lipid, amino acid and nucleotide metabolism provides key focal points for developing new therapies, we here turn our attention to glycolysis and the TCA cycle to provide examples of how metabolic intermediates and enzymes can provide potential novel therapeutic targets.
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The pharmaceutical management of cardiac allograft vasculopathy after heart transplantation.
Spitaleri, G, Farrero Torres, M, Sabatino, M, Potena, L
Expert opinion on pharmacotherapy. 2020;(11):1367-1376
Abstract
INTRODUCTION Cardiac allograft vasculopathy (CAV) is a major limitation to long-term survival after heart transplantation. Its peculiar pathophysiology involves multifactorial pathways including immune-mediated and metabolic risk factors, which are associated with the development of specific pathological lesions. The often diffuse and chronic nature of the disease reduces the effectiveness of revascularization procedures, and pharmacological prevention of the disease is the sole therapeutic approach with some proven efficacy. AREAS COVERED In this article, after briefly outlining the risk factors for CAV, the authors revise the potential pharmacological approaches that may reduce the burden of CAV. While several therapies have shown convincing efficacy in terms of CAV prevention diagnosed by coronary imaging, very few have been reported to improve prognosis with any meaningful level of evidence. EXPERT OPINION The authors believe that a customizable approach is necessary for clinical practice given the currently available evidence. Furthermore, it is important, in the future, to address the glaring therapeutic gap of an effective treatment against donor-specific antibodies, whose effect on endothelial injury is currently one of the major mechanisms of CAV development and for which no pharmacological treatment is currently available.
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Efficacy of microneedling combined with tacrolimus versus either one alone for vitiligo treatment.
Ebrahim, HM, Albalate, W
Journal of cosmetic dermatology. 2020;(4):855-862
Abstract
BACKGROUND Combination therapies have reported to augment the repigmentation in vitiligo. Microneedling (Mn) facilitates drug delivery across the skin barrier. OBJECTIVE To evaluate and compare the efficacy and safety of Mn combined with tacrolimus vs Mn alone or tacrolimus 0.1% ointment for treatment of localized and stable vitiligo. PATIENTS AND METHOD Ninety patients with vitiligo were randomized into three groups: group I received microneedling with tacrolimus, group II microneedling only both at 2 weeks interval for twelve sessions, and group III applied tacrolimus ointment 0.1% twice daily for 6 months. Skin biopsies were taken at baseline and after treatment. RESULTS The overall improvement (76.6%) was significantly higher in the combined group compared with other groups. Repigmentation was excellent in 66.6 of group I vs 33.3% in the other two groups (P .03). A highly significant improvement of the extremities was observed in the combined group than in the other groups (P < .001). A fewer number of sessions have reported in the combined group (I) than in the microneedling group (II; P < .001). Immunohistochemical results showed a significantly higher expression of HMB-45 in group I than in other two groups (P .04). Side effects were mild and tolerable in all groups. CONCLUSION The combination group has shown promising results over the other two groups.