Associations between continuous glucose monitoring (CGM) metrics and psycholinguistic measures: a correlational study.

AIM: Recently, the relationship between diabetes and mental health has been widely studied. With the advent of continuous glucose monitoring (CGM), some researchers have been interested in exploring the association between glucose-related metrics and psychological aspects. These studies have primarily relied on self-report questionnaires which present some limitations. Therefore, the present multicenter study aims at testing potential associations between CGM metrics and affective processes derived from narratives about using a CGM sensor. METHODS: An exploratory correlational design was used. Fifty-eight adults with type 1 diabetes using CGM were enrolled and invited to complete an online survey, where they replied to an open-ended question regarding their personal experience with the CGM sensor. Texts derived from the answers were analyzed through Linguistic Inquiry and Word Count, a widely used text analysis tool that can automatically identify and quantify linguistic patterns related to various psychological dimensions. Psycholinguistic measures were correlated with CGM metrics. RESULTS: Higher levels of sadness/depression correlated with lower %TIR (r = - 339; p < .01) and higher %TAR (r = .342; p < .01). CONCLUSIONS: The study highlights the relationship between CGM metrics and psychological variables derived from patients' narratives. In particular, it is possible to hypothesize a positive role of %TIR in reducing depressive feelings in individuals with diabetes, as well as a negative role of depressive feelings in achieving desirable CGM outcomes. Additionally, there is a potential role of glycemic variability, particularly hyperglycemia, in the expression of depressive and sad feelings, which has been less studied compared to the effects of hypoglycemia.

Understanding care relationships in diabetes practice: A psychodynamic interview-based exploratory study.

OBJECTIVE: To explore the subjective experience of physicians working in diabetic settings about their care relationships in order to find some unique clues contributing to physician professional health and capacity to manage patients' adherence. RESEARCH DESIGN AND METHODS: An interview-based exploratory study has been carried out involving 18 physicians (77.8% female) with at least 3 years of clinical practice in diabetes care. In-depth interviews about the emotional experience with patients with diabetes were conducted and audio recorded. Interviews transcripts were analyzed through a computer-based text analysis which allowed the identification of thematic domains (Cluster Analysis) and latent factors (Correspondence Analysis) viewed through a psychodynamic and constructivist lens. RESULTS: Six thematic domains emerged respectively referring to: Concern (8.43%), Control (14.42%), Ambivalence (22.08%), Devotion (22.49%), Guilt (19.29%) and Strive for Achievement (13.30%). Moreover, three latent dimensions were taken into account, which explained 69.20% of data variance: Affect Repression (28.50%), Tendency to Repair (22.70%) and Anxiety Pattern (18.00%). CONCLUSIONS: Overall, the results of the present study confirm the challenging nature of diabetes care. In particular, physicians ongoing effort to restore patients' psychological integrity in chronic condition constitute the most novel finding above all. In this regard, the need for emotional labor in physicians' education and training is suggested in order to both prevent burnout symptoms (e.g. depersonalization) and promote shared decision making in care relationships. However, findings should be treated as preliminary given the convenience nature of the sample and its reduced size.

Overshoot of the Respiratory Exchange Ratio during Recovery from Maximal Exercise Testing in Kidney Transplant Recipients.

The overshoot of the respiratory exchange ratio (RER) during recovery from exercise has been found to be reduced in magnitude among patients with heart failure. The aim of this study is to investigate whether this phenomenon could also be present in patients with peripheral, and not cardiac, limitations to exercise such as kidney transplant recipients (KTRs). In this retrospective cross-sectional study, KTRs were evaluated with maximal cardiopulmonary exercise testing (CPET) assessing the RER overshoot parameters during recovery: the RER at peak exercise, the maximum RER value reached during recovery, the magnitude of the RER overshoot (RER mag = (RER max-peak RER)/peak RER%) and the linear slope of the RER increase after the end of exercise. A total of 57 KTRs were included in the study (16 females), all of them showing a significant RER overshoot (RER mag: 28.4 ± 12.7%). Moreover, the RER mag showed significant correlations with the fitness of patients (peak VO2: ρ = 0.57, p < 0.01) and cardiorespiratory efficiency (VE/VCO2 slope: r = -0.32, p < 0.05; oxygen uptake efficiency slope (OUES): r = 0.48, p < 0.01). Indeed, the RER mag was significantly different between the subgroups stratified by Weber's fitness class or a ventilatory efficiency class. Our study is the first to investigate recovery of the RER in a population of KTRs, which correlates well with known prognostic CPET markers of cardiorespiratory fitness, determining the RER mag as the most meaningful RER overshoot parameter. Thus, the RER recovery might be included in CPET evaluations to further improve prognostic risk stratifications in KTRs and other chronic diseases.

Extreme Desire for Motherhood: Analysis of Narratives From Women Undergoing Assisted Reproductive Technology (ART).

The problem of infertility and its consequent treatment (denoted as Assisted Reproductive Technology or ART) represent an increasing phenomenon, especially in industrialized countries. Confronting with one's own procreative limitations can generate strong negative emotional reactions. This study aims at understanding how the desire for motherhood manifests itself in infertile women undergoing ART, studying their emotional and subjective perspective. An in-depth explorative research study was conducted on 17 infertile women attending an Italian hospital clinic for fertility treatment. Emotional text analysis was conducted to analyze the corpus of their interviews, allowing the identification of four thematic domains (clusters) which refer, respectively, to the following emotional dimensions: an inclination to self-sacrifice, seen as the price to be paid for the desired success of the treatment (Cluster 1), pursuit of inclusion in the world of procreative mothers (Cluster 2), precarious equilibrium between the deep desire for a baby and the withdrawal from the treatment (Cluster 3), surrender to any possible consequence in order to obtain the desired mother-child relationship (Cluster 4). The witness of the couples' suffering for their condition of infertility and their strong desire for parenting can represent a source of high pressure for the fertility care staff, as they are the only ones responsible for the fulfillment of the great dream of biological parenthood. For these reasons, a multidisciplinary approach, which involves psychological as well as medical experts all working together, could benefit both the patients and the healthcare professionals and improve the quality of the reproductive healthcare services.

Pathophysiology of Post Transplant Hypertension in Kidney Transplant: Focus on Calcineurin Inhibitors Induced Oxidative Stress and Renal Sodium Retention and Implications with RhoA/Rho Kinase Pathway.

Post-transplant hypertension is a common occurrence during treatment with calcineurin inhibitors (CNIs) in kidney transplant population. The pathogenesis of vasoconstriction induced by CNIs involves vascular tone alterations and kidney sodium transport regulation. Among the factors involved a key role is played by the activation of intrarenal renin-angiotensin system with enhanced release of Angiotensin II (Ang II) and increase of oxidative stress. A common pathway between oxidative stress and hypertension induced by CNIs may be identified in the involvement of the activation of RhoA/Rho kinase pathway, key for the induction of hypertension and cardiovascular-renal remodeling, of the oxidative stress mediated increased nitric oxide (NO) metabolism and increased renal sodium retention via increased activity of thiazide-sensitive sodium chloride cotransporter (NCC) in the distal tubule. We examined literature data including those coming from our group regarding the role of oxidative stress and sodium retention in CNIs induced hypertension and their involvement in cardiovascular-renal remodeling. Based on the available data, we have provided support to the activation of RhoA/Rho kinase pathway as an important effector in the pathophysiology of CNIs induced post-transplant hypertension via activation of oxidative stress and sodium retention. Clarification of how the biochemical and molecular mechanisms that regulate the processes involved in CNIs induced post transplant hypertension work and interact, would provide further insights not only into the comprehension of the pathophysiology of CNIs induced post transplant hypertension but could also have a positive impact on the clinical ground through the identification of significant targets. Their specific pharmacologic targeting might have multiple beneficial effects on the whole cardiovascular-renal function. The demonstration that in kidney transplanted patients with CNIs induced post-transplanted hypertension, the treatment of hypertension with different antihypertensive drugs inducing a comparable blood pressure reduction but different effects for example on oxidative stress and oxidative stress related proteins and/or Rho kinase and sodium retention, could be helpful for the choice of the antihypertensive treatment in these patients which takes advantage from effects of these drugs beyond blood pressure reduction.

Hepatitis C virus infection in end-stage renal disease and kidney transplantation.

Liver disease secondary to chronic hepatitis C virus (HCV) infection is an important cause of morbidity and mortality in patients with end-stage renal disease (ESRD) on renal replacement therapy and after kidney transplantation (KT). Hemodialytic treatment (HD) for ESRD constitutes a risk factor for bloodborne infections because of prolonged vascular access and the potential for exposure to infected patients and contaminated equipment. Evaluation of HCV-positive/ESRD and HCV-positive/KT patients is warranted to determine the stage of disease and the appropriateness of antiviral therapy, despite such treatment is challenging especially due to tolerability issues. Antiviral treatment with interferon (IFN) is contraindicated after transplantation due to the risk of rejection, and therefore, treatment is recommended before KT. Newer treatment strategies of direct-acting antiviral agents in combination are revolutionizing HCV therapy, as a result of encouraging outcomes streaming from recent studies which report increased sustained viral response, low or no resistance, and good safety profiles, including preservation of renal function. KT has been demonstrated to yield better outcomes with respect to remaining on HD although survival after KT is penalized by the presence of HCV infection with respect to HCV-negative transplant recipients. Therefore, an appropriate, comprehensive, easily applicable set of clinical practice management guidelines is necessary in both ESRD and KT patients with HCV infection and HCV-related liver disease.

Comparison of cytomegalovirus (CMV) enzyme-linked immunosorbent spot and CMV quantiferon gamma interferon-releasing assays in assessing risk of CMV infection in kidney transplant recipients.

Assessing cytomegalovirus (CMV)-specific cell-mediated immunity (CMI) represents an appealing strategy for identifying transplant recipients at risk of infection. In this study, we compared two gamma interferon-releasing assays (IGRAs), Quantiferon-CMV and CMV enzyme-linked immunosorbent spot (ELISPOT), to determine the ability of each test to predict protective CMV-specific T-cell responses. Two hundred twenty-one Quantiferon-CMV and ELISPOT tests were conducted on 120 adult kidney transplant recipients (KTRs), including 100 CMV-seropositive transplant recipients (R+) and 20 CMV-seronegative transplant recipients of a CMV-positive donor (D+/R-). As a control cohort, 39 healthy adult subjects (including 33 CMV-seropositive and 6 CMV-seronegative subjects) were enrolled. CMV IgG serology was used as a reference for both tests. In the CMV-seropositive individuals, the ELISPOT and Quantiferon-CMV assays provided 46% concordance with the serology, 12% discordance, 18% disagreement between ELISPOT or Quantiferon-CMV and the serology, and 24% gray areas when one or both tests resulted in weak positives. None of the CMV-seronegative subjects showed detectable responses in the ELISPOT or the Quantiferon-CMV test. In transplant recipients, both the ELISPOT and Quantiferon-CMV assays positively correlated with each other and negatively correlated with CMV DNAemia in a significant way (P<0.05). During the antiviral prophylaxis, all 20 D+/R- KTRs we examined displayed undetectable Quantiferon-CMV and ELISPOT results, and there was no evidence of CMV seroconversion. The receiving operator curve (ROC) statistical analysis revealed similar specificities and sensitivities in predicting detectable viremia (areas under the curve [AUC], 0.66 and 0.62 for Quantiferon-CMV and ELISPOT, respectively). ELISPOT and Quantiferon-CMV values of >150 spots/200,000 peripheral blood mononuclear cells (PBMCs) and >1 to 6 IU gamma interferon (IFN-γ) were associated with protection from CMV infection (odds ratios [OR], 5 and 8.75, respectively). In transplant recipients, the two tests displayed similar abilities for predicting CMV infection. Both the ELISPOT and Quantiferon-CMV assays require several ameliorations to avoid false-negative results.

Persistent secondary hyperparathyroidism and vertebral fractures in kidney transplantation: role of calcium-sensing receptor polymorphisms and vitamin D deficiency.

Bone morbidity remains a major problem even after successful renal transplantation. We investigated the role of calcium-sensing receptor (CaSR) polymorphisms and 25-hydroxyvitamin D levels on the persistence of secondary hyperparathyroidism (SHPT) and their relationships with vertebral fractures (VFx) in 125 renal allograft recipients transplanted 44 +/- 23 months before. All patients underwent evaluation of the main biochemical parameters of calcium metabolism as well as vertebral and femoral bone density. In 87 patients, CaSR polymorphisms (A986S, R990G, and Q1011E) also were assessed. X-ray images of the lateral spine were obtained in 102 subjects to perform vertebral morphometry. High parathyroid hormone (PTH) and 25-hydroxyvitamin D lower than 80 nmol/L were found in 54% and 97% of patients, respectively, with 40% of these showing vitamin D levels lower than 30 nmol/L. VFx were detected in 57% of the subjects. After multiple adjustments, 25-hydroxyvitamin D, age, and hemodialysis duration, but not CaSR polymorphisms, were found to be significant predictors of high PTH, whereas age and time since transplant were positively related with lower 25-hydroxyvitamin D values. PTH and time since transplant were significantly associated with VFx. Patients with two or more VFx showed serum PTH levels 50% higher than patients without fractures. We therefore conclude that persistent SHPT is a very common feature after renal transplantation and that, unlike CaSR polymorphisms, low 25-hydroxyvitamin D is involved in its pathogenesis. High PTH levels, in turn, are associated with an increased VFx risk, which confirms the need for strategies aimed at lowering serum PTH in this setting as well.

Dual kidney transplantation after liver transplantation: a good option to rescue a patient from dialysis.

Chronic renal failure (CRF) due to calcineurin inhibitor (CNI) nephrotoxicity is one of the most serious side effects influencing mortality and morbidity after liver transplantation (LTx). One way to offer a longer survival and better quality of life to LTx recipients who develop CRF is kidney transplantation, though this is not feasible for all candidates due to the shortage of organs. With changes in the characteristics of the global donor pool, which includes increasing number of elderly donors, both kidneys from one older donor are transplanted into the same adult recipient (dual kidney transplantation, DKT) to offset the lower nephron mass. DKT might be an option after LTx to rescue a patient from dialysis, with consequent survival benefits. We report on two cases of DKT after LTx in patients with CRF who were on dialysis due to CNI nephrotoxicity.

Agalsidase therapy in patients with Fabry disease on renal replacement therapy: a nationwide study in Italy.

BACKGROUND: In Fabry disease, end-stage renal disease (ESRD) and severe neurologic and cardiac complications represent the leading causes of late morbidity and mortality. A comprehensive Italian nationwide survey study was conducted to explore changes in cardiac status and renal allograft function in Fabry patients on renal replacement therapy (RRT) and enzyme replacement therapy (ERT). METHODS: This study was designed as a cross-sectional survey study with prospective follow-up. Of the 34 patients identified via searches in registries, 31 males and 2 females who received RRT and ERT (agalsidase beta in 30 patients, agalsidase alpha in 3) were included. Left ventricular mass index (LVMI), interventricular septal thickness at end diastole (IVSD), left ventricular posterior wall thickness (LVPWT) and renal allograft function were assessed at ERT baseline and subsequently at yearly intervals. RESULTS: The patients in the dialysis and transplant groups had been started on dialysis at age 42.0 and 37.1 years (mean), respectively, and patients in the transplant group received their renal allograft at age 39.8 years (mean). The mean age at the start of ERT was similar, 44.1 and 44.6 years, respectively. The mean RRT follow-up was 61.1 and 110.6 months for dialysis and transplant patients, respectively, whereas the ERT duration was 45.1 and 48.4 months, respectively. Cardiac parameters increased in dialysis patients. In transplant patients, mean LVMI seemed to plateau during agalsidase therapy at a lower level as compared to baseline. Decline in renal allograft function was relatively mild (-1.92 ml/min/year). Agalsidase therapy was well tolerated. Serious ERT-unrelated events occurred more often in the dialysis group. CONCLUSIONS: Kidney transplantation should be the standard of care for Fabry patients progressing towards ESRD. Transplanted Fabry patients on ERT may do better than patients remaining on maintenance dialysis. Larger, controlled studies in Fabry patients with ESRD will have to demonstrate if ERT is able to change the trajectory of cardiac disease and can preserve graft renal function.

Calcineurin inhibitor-free immunosuppression in dual kidney transplantation from elderly donors.

BACKGROUND: Kidneys from expanded-criteria donors may be particularly susceptible to calcineurin inhibitor (CI)-mediated vasoconstriction and nephrotoxicity. In the early post-transplant phase, using CI may prolong ischemic injury and, in the long term, chronic CI nephrotoxicity is an even greater concern. To avoid the acute and chronic consequences of CI in kidneys from marginal donors, CI-free protocols have been introduced for maintenance immunosuppressive therapy. A CI-free protocol of anti-thymocyte globulin (ATG) induction, sirolimus, mycophenolate mofetil (MMF) and steroids has been adopted at our center in recipients of dual kidney transplantation (DKT) from elderly donors (EDs). METHODS: Dual kidney transplantations performed since April 2003 on CI-free immunosuppression (group 1 = 31) were compared with earlier DKTs in recipients treated with CI-based therapy (group 2 = 25), retrospectively analyzing patient and graft survival, surgical and medical complications, rejection episodes and renal function. RESULTS: No deaths occurred after a mean follow-up of 10.1 +/- 7.6 (group 1) and 48.2 +/- 17.4 months (group 2). Graft loss occurred in one patient in group 1 (bilateral renal vein thrombosis) and in three patients in group 2 (one primary non-function [PNF], one chronic rejection, one Kaposi's sarcoma). The incidence of acute rejection was 19% in group 1 and 16% in group 2. Delayed graft function (DGF) was recorded in 16% and 48%, respectively. Renal function was better in group 1, with a mean S-Cr of 135 +/- 48 vs. 210 +/- 141 micromol/L at one month and 116 +/- 30 vs. 149 +/- 49 micromol/L at six months. CONCLUSIONS: After DKT from EDs, a CI-free immunosuppressive regimen including ATG induction, sirolimus, MMF and steroids affords excellent results, with a lower DGF rate and a better renal function.

Perforin, Granzyme B, and fas ligand for molecular diagnosis of acute renal-allograft rejection: analyses on serial biopsies suggest methodological issues.

BACKGROUND: The Perforin-Granzyme B and Fas/Fas Ligand apoptotic mechanisms are involved in the development of acute renal rejection (AR). We describe our experience of analyzing the expression of cytotoxic T-lymphotoxins (CTL) in biopsies and peripheral blood leukocytes (PBL) for the diagnosis of AR. METHODS: We analyzed Perforin (P), Granzyme B (GB) and Fas Ligand (FL) expression in 68 renal biopsies and 64 PBL using comparative kinetic RT-PCR and, for GAPDH and FL, we also replicated with real-time RT-PCR. The levels of expression were measured in different groups, such as T0 (biopsies before reperfusion and PBL in recipient before the transplant [Tx]), Td (biopsies and PBL collected for clinical purposes) and Tp (biopsies and PBL two months after Tx). RESULTS: A higher CTL expression was seen in non-rejecting (NR) biopsies in the first 2 months after Tx. P and FL were significantly more expressed during AR in all biopsies and in Td, while P remained upregulated in Tp. In PBL, there was no significant increase in CTL transcription during AR. A variable expression of CTL emerged in all T0 biopsies. CONCLUSIONS: Two lytic pathways are activated in biopsies when AR occurs shortly after Tx, whereas the P/GB mechanism prevails if it occurs later on. Only P and FL in biopsies might be able to predict AR diagnosis, but with a considerable variability in each sample, possibly due to the small portion of tissue core, which may be inadequate for molecular diagnosis. CTL expression in PBL does not correlate with histological AR.

Incidence of second primary cancer in transplanted patients.

BACKGROUND: Solid organ transplanted patients have a three- to fourfold higher lifetime risk of developing a cancer than the general population. However, the incidence of a second primary cancer in transplanted patients has never been studied, despite the fact that the presence of regular follow-ups and the increased survival of these patients make them a very attractive model. METHODS: We investigated the incidence of a second primary cancer (SPC) in 7,636 patients who underwent a kidney, liver, lung or heart transplant between 1970 and 2004, and were followed-up for 51,819 person-years. RESULTS: During the follow-up, 499 subjects developed a first cancer (annual incidence: 98.6 x 10,000 PY), and 22 of them developed a SPC (annual incidence: 3.9 x 10,000 PY). The annual incidence of a SPC in the transplanted patients who developed a first cancer was 107.8 x 10,000 PY, giving a standardized incidence ratio of 1.1 (95% CI: 0.83-1.41). CONCLUSIONS: This result shows that the incidence of the SPC was the same as the incidence of a first cancer. Our study does not indicate an increased risk of SPC in transplanted subjects who already suffered a first malignancy.

Secondary hyperparathyroidism is associated with vitamin D receptor polymorphism and bone density after renal transplantation.

Immunosuppresive treatment and secondary hyperparathyroidism (SHPT) are considered among the most important pathogenetic factors for post-renal transplant bone disease. The aim of this study was to investigate the relationships among vitamin D receptor (VDR) gene polymorphism, parathyroid hormone (PTH) levels and bone density in renal transplant recipients. We enrolled 75 patients (50 male and 25 female, mean age 47+/-11 years) who had undergone kidney transplantation 53+/-4 months before. All patients underwent an evaluation of the main biochemical parameters of bone metabolism as well bone densitometry. VDR alleles were typed by a PCR assay based on a polymorphic BsmI restriction site. When patients were categorized according to the VDR genotype (BB, Bb, bb), serum creatinine and the cumulative doses of immunosuppressive drugs were similar across the groups. PTH levels higher than 80 pg/ml were found in 53.6% of the patients, with the highest values being detected in the bb VDR genotype (P<0.05). PTH was significantly correlated to urinary NTx values. Bone density was low in the whole population; however, spinal bone density was lower in the bb subgroup (P<0.02). In the whole population, only PTH (P<0.05) and body mass index (P<0.01) were independent predictors of spinal bone density. Grouping patients by the VDR gene polymorphism, only PTH continued to be an independent predictor of spinal bone density in the bb allele subgroup (R(2) Adj.=0.17). We can conclude that the VDR genotype polymorphism affects bone density of renal transplant recipients via its effects on the severity of SHPT.

Use of a BJAB-derived cell line for isolation of human herpesvirus 8.

Establishment of latently infected cell lines from primary effusion lymphomas (PEL) presently is the most efficient system for the propagation of clinical strains of human herpesvirus 8 (HHV-8) in culture. Here we describe a new approach to culture productively replicating HHV-8 from patient samples. A BJAB-derived B-cell line, BBF, was found to retain HHV-8 longer, to support the latent and lytic replication programs, and to produce transmissible virus. Supernatants from n-butyrate-treated peripheral blood mononuclear cells of 24 HHV-8-seropositive renal transplant recipients were used to infect BBF cells, and replicating virus was detected in cultures from 11 patients. Moreover, BBF cells infected with saliva strains showed a highly productive profile regardless of the initial viral load, which confirms that infectious HHV-8 can be present in saliva and also suggests that saliva strains may exhibit a high tropism for B lymphocytes. In conclusion, we established an in vitro system that efficiently detects HHV-8 in samples with low viral loads and that produces infectious progeny. BBF cells can be used to propagate HHV-8 from different biological samples as well as to clarify important issues related to virus-cell interactions in a context distinct from endothelial and PEL-derived cell lines.

Renal transplantation. Strategies to prevent organ rejection--the role of an inter-regional reference center.

This paper summarizes the role of the Inter-Regional Reference Center (RC) of the North Italy Transplant program (NITp), in coordinating a donor procurement and organ transplantation network, with a special focus on the strategies to minimize immunological risk and complications after transplantation. In the NITp, patients enrolled on the renal transplantation (RT) waiting list are typed for HLA-A,B,DRB1 antigens with a genomic method. They are periodically screened for the presence of lymphocytotoxic antibodies in their serum by the RC and their suitability to receive the transplant is checked periodically. Cadaver kidney allocation is ruled by a computerized algorithm, named NITK3, established in 1997, which aims at ensuring quality, equity, transparency and traceability during all the phases of the allocation decision-making process. NITK3 has been set up by the NITp Working Group on the basis of biological, medical and administrative criteria and it is periodically reviewed after the analysis of transplant results. In this paper, we show the results of a preliminary analysis of RTs performed from 1998 to 2002 in nine out of sixteen centers of the NITp area, which demonstrates the general quality of the NITp program in terms of patients and graft survival and the special attention to the patients at higher immunological risk.