Drug-eluting stent insertion in the treatment of in-stent renal artery restenosis in three renal transplant recipients

Percutaneous transluminal angioplasty (PTA) with or without stent insertion is the treatment of choice in transplant renal artery stenosis. However, in-stent restenosis occurs in as many as 13% of patients after PTA and stent insertion. This article describes three patients with recurrent transplant renal artery in-stent stenosis who were treated with paclitaxel-eluting stents. In two patients, the transplant renal artery remained patent after insertion of the drug-eluting stent (DES), and one patient required balloon angioplasty 7 months after the DES was inserted.     

The current status of anti-GPCR drugs against different cancers

G protein coupled receptors (GPCRs) have emerged as the most potential target for a number of drug discovery programs ranging from control of blood pressure, diabetes, cure for genetic diseases to treatment of cancer. A panel of different ligands including hormones, peptides, ions and small molecules is responsible for activation of these receptors. Molecular genetics has identified key GPCRs, whose mutations or altered expressions are linked with tumorgenicity. In this review, we discussed recent advances regarding the involvement of GPCRs in the development of cancers and approaches to manipulating the mechanism behind GPCRs involved tumor growth and metastasis to treat different types of human cancer. This review provides an insight into the current scenario of GPCR-targeted therapy, progress to date and the challenges in the development of anticancer drugs.     

Clinical outcomes from bilateral versus unilateral stimulation of the pedunculopontine nucleus with and without concomitant caudal zona incerta region stimulation in Parkinson's disease

Abstract Introduction. The Pedunculopontine nucleus is a novel target for deep brain stimulation and this may improve postural instability and gait dysfunction in Parkinson's disease. If unilateral Pedunculopontine nucleus stimulation is as efficacious as bilateral stimulation this would lead to less surgical risk. Methods. 5 Parkinson's disease patients with bilateral caudal Zona Incerta region and Pedunculopontine nucleus electrodes were assessed using the motor component of the Unified Parkinson's Disease Rating Scale. Patients were assessed in the on-medication state to determine the optimal combination of stimulation setting for axial symptom control. Results. The on-medication composite axial-subscore only showed a statistically significant improvement when bilateral Pedunculopontine nucleus and caudal Zona Incerta region stimulation was used. Conclusions. In the on-medication state bilateral Pedunculopontine nucleus and caudal Zona Incerta region stimulation is required in order to produce a significant change in the motor Unified Parkinson's Disease Rating Scale axial-subscore from baseline.     

Provider interaction with the electronic health record: The effects on patient-centered communication in medical encounters

Objective

The computer with the electronic health record (EHR) is an additional ‘interactant’ in the medical consultation, as clinicians must simultaneously or in alternation engage patient and computer to provide medical care. Few studies have examined how clinicians’ EHR workflow (e.g., gaze, keyboard activity, and silence) influences the quality of their communication, the patient's involvement in the encounter, and conversational control of the visit.

Methods

Twenty-three primary care providers (PCPs) from USA Veterans Administration (VA) primary care clinics participated in the study. Up to 6 patients per PCP were recruited. The proportion of time PCPs spent gazing at the computer was captured in real time via video-recording. Mouse click/scrolling activity was captured through Morae, a usability software that logs mouse clicks and scrolling activity. Conversational silence was coded as the proportion of time in the visit when PCP and patient were not talking. After the visit, patients completed patient satisfaction measures. Trained coders independently viewed videos of the interactions and rated the degree to which PCPs were patient-centered (informative, supportive, partnering) and patients were involved in the consultation. Conversational control was measured as the proportion of time the PCP held the floor compared to the patient.

Results

The final sample included 125 consultations. PCPs who spent more time in the consultation gazing at the computer and whose visits had more conversational silence were rated lower in patient-centeredness. PCPs controlled more of the talk time in the visits that also had longer periods of mutual silence.

Conclusions

PCPs were rated as having less effective communication when they spent more time looking at the computer and when there was more periods of silence in the consultation. Because PCPs increasingly are using the EHR in their consultations, more research is needed to determine effective ways that they can verbally engage patients while simultaneously managing data in the EHR.

Practice implications

EHR activity consumes an increasing proportion of clinicians’ time during consultations. To ensure effective communication with their patients, clinicians may benefit from using communication strategies that maintain the flow of conversation when working with the computer, as well as from learning EHR management skills that prevent extended periods of gaze at computer and long periods of silence. Next-generation EHR design must address better usability and clinical workflow integration, including facilitating patient-clinician communication.     

Impaired Direct Priming of CD8 T Cells by Donor-Derived Cytomegalovirus Following Kidney Transplantation

Cytomegalovirus (CMV) infection increases the risk of complications after renal transplantation, but the mechanisms controlling donor-derived infection are not adequately characterized. Here, we assessed the risk of clinically significant CMV disease in donor-seropositive, recipient-seropositive (D+R+) renal transplantation and examined recipients’ CMV antigen-specific cellular immune responses primed directly by donor cells. In a retrospective cohort of 569 patients administered standardized basiliximab-tacrolimus-mycophenolate-corticosteroid immunosuppressive therapy, CMV disease rates increased in D+R+ serostatus pairings compared with D−R+ pairings (hazard ratio [HR], 2.61; 95% confidence interval [CI], 1.36 to 5.01; P=0.004) and associated with increased donor-recipient HLA mismatch in the D+R+ group (HR [per class 1 mismatch], 1.43; 95% CI, 1.12 to 1.82]; P=0.02). D+R+ and D+R− transplants in which the donor and recipient differentially expressed at least one HLA class I allele were followed prospectively from the time of transplantation. During the first year after transplantation, four of eight seropositive recipients and one of three seronegative recipients displayed peripheral blood CD8+ T cell responses to CMV presented by recipient-specific HLA. Notably, no recipients mounted responses to CMV presented by donor-specific HLA, despite the detection of CMV antigen expression in all seropositive donor organs examined (n=10), suggesting that the allograft of Class I HLA-mismatched seropositive donors is inaccessible to CD8+ T cell responses. Finally, pretransplant assays of anti-CMV cellular immunity predicted post-transplant CMV replication less accurately in D+R+ pairings than in D−R+ pairings, possibly reflecting in vitro assay specificity for recipient, rather than donor, HLA. These findings are relevant to the clinical management and immunologic understanding of donor-transmitted viral infection.Cytomegalovirus (CMV) infection remains an important complication of kidney transplantation, being associated with increased graft failure rates, morbidity, and mortality. Although the cellular immune response to CMV, especially the CD8+ T cell response, is of primary importance in controlling infection,^1–3 the CMV-specific antibody serostatus of donor (D) and recipient (R) is a useful surrogate to aid in risk stratification because it identifies individuals with latent CMV infection that may subsequently reactivate. High disease rates in primary infection (D+R− transplantation) are well recognized, and requirement for antiviral prophylaxis in this context is largely uncontested. CMV disease is also seen in seropositive recipients (R+) and may occur irrespective of donor serostatus. Seropositive recipients are often grouped together as “intermediate risk,” irrespective of donor serostatus. However, historical evidence suggests that D+R+ transplantation is associated with increased disease rates compared with D−R+ transplantation.⁴ Also, two recent trials^5,6 and a single-center study⁷ showed higher infection rates in D+R+ than in D−R+ transplantation. Because these latter studies focused on (often asymptomatic) CMV infection, rather than symptomatic disease, and because all used antiviral prophylaxis or pre-emptive therapy for CMV infection, it remains unclear whether disease rates differ between D+R+ and D−R+ transplantation, particularly under contemporary immunosuppression without antiviral prophylaxis.After D+R+ transplantation, some CMV cases may result from donor-derived infection, although the mechanism behind this is incompletely understood.^4,8 Although lack of protective immunity to newly infecting strains may be important,⁹ other mechanisms may also play a role. For example, HLA mismatch between donor and recipient may result in failure of “cognate” immunity to control viral infection in donor tissue. In this regard, clinical data are conflicting, with studies from the 1980s and 1990s suggesting increased CMV disease rates with increased HLA class II mismatch^10,11 but others suggesting reduced rates in this setting.^12,13 One of these studies also identified HLA class I mismatch as a risk factor for disease.¹¹The initial purpose of this study was to evaluate the effect of donor CMV serostatus on disease risk in seropositive recipients and whether HLA class I mismatch modifies the risk. We then used HLA-peptide tetramers to determine the specificity of cellular immunity to defined CMV peptides presented through donor or recipient HLA alleles and examined the development of T cell responses (or lack of them) against CMV primed “directly” on donor cells. These findings should be of value in the clinical management of CMV infection in this setting and are of considerable interest in further the understanding of the mechanism of viral infection in solid organ transplantation.     

Validity of glycated haemoglobin to diagnose new onset diabetes after transplantation

Diagnosing new onset diabetes after transplantation (NODAT) by glycated haemoglobin (HbA1c) has not been validated against the gold‐standard oral glucose tolerance test (OGTT). We analysed the predictive and optimum value of HbA1c to diagnose NODAT amongst nondiabetic renal transplant recipients. Assessment of glucose metabolism (OGTT and HbA1c) was prospectively undertaken at 3 and 12 months post‐transplantation in 71 nondiabetic renal transplant recipients. Receiver operator characteristic (ROC) curve analyses were performed to determine accuracy, sensitivity, specificity and area under curve (c‐statistic). Incidence of NODAT at 3 and 12 months post‐transplantation was 14.3% and 9.5% respectively. At 3 months, optimum HbA1c cut‐off value for predicting NODAT based on fasting glucose was 7.35 [AUC 1.00 (sensitivity 100.0%, specificity 100.0%, P = 0.004)] and for postprandial glucose‐defined NODAT was 6.20 [AUC 0.98 (sensitivity 100.0%, specificity 88.9%, P < 0.001)]. At 12 months, optimum HbA1c cut‐off value for both fasting‐ and postprandial glucose‐defined NODAT was 6.45 [AUC 0.92 (sensitivity 100.0%, specificity 87.5%, P = 0.048) and AUC 0.84 (sensitivity 75.0%, specificity 89.5%, P = 0.026) respectively]. Concordance between diagnosis of NODAT (OGTT+, HbA1c+) and nondiagnosis of NODAT (OGTT?, HbA1c?) was 88.9% and 98.7% respectively. To conclude, HbA1c (≥6.5%) can be utilized to diagnose NODAT beyond 3 months post‐transplantation but the OGTT remains the gold‐standard tool.