The relationship between Parkinson's disease and sexual hyperactivity secondary to drug treatment: A systematic review.

INTRODUCTION: This review addresses the prevalence of hypersexual behavior in Parkinson's patients and the underlying neurobiological mechanisms, identifying risk and protective factors, comparing incidence among different treatments, and proposing recommendations for management and prevention. OBJECTIVE: To conduct a review on the relationship between Parkinson's disease and hypersexual behavior as a result of pharmacological treatment. METHODOLOGY: The search strategy, guided by PRISMA and PICOS criteria, focuses on the correlation between Parkinson's disease and hypersexual behavior due to pharmacological treatment. Utilizing databases like PubMed and Proquest, studies from the last 10 years in English or Spanish were selected, emphasizing clinical trials with Parkinson's patients under treatment. Inaccessible, irrelevant, or mixed-sample studies were excluded. The Cochrane Scale assessed the risk of bias. RESULTS: Out of 122 records, 103 remained after eliminating duplicates; 48 were reviewed, and ultimately, 6 studies met the inclusion criteria for analysis. CONCLUSIONS: Synthesizing the risk and protective factors linked to hypersexual behavior in Parkinson's patients receiving pharmacological treatment underscores the critical need for early detection and incorporation of these factors into clinical care. The suggested guidelines for managing and preventing hypersexual behavior in these patients carry substantial practical implications.

Antioxidant Active Phytochemicals in Ternstroemia lineata Explained by Aquaporin Mechanisms.

The antioxidant action of terngymnoside C (1) and hydroxytyrosol-1-glucoside (2), isolated for the first time from the flower buds of Ternstroemia lineata, as well as katsumadin (3), obtained from the seedless fruits, was evaluated using ABTS•+ and H2O2-Saccharomyces cerevisiae models. In silico docking analysis of 1, 2, and 3 determined their affinity forces to the aquaporin monomers of the modeled S. cerevisiae protein 3 (AQP3) and human protein 7 (AQP7) channels that regulate the H2O2 cell transport. The ABTS•+ antiradical capacity of these compounds showed IC50 values of 22.00 µM (1), 47.64 µM (2), and 73.93 µM (3). The S. cerevisiae antioxidant assay showed that at 25 µM (1) and 50 µM (2 and 3), the cells were protected from H2O2-oxidative stress. These compounds, together with quercetin and vitamin C, were explored through the modeled S. cerevisiae AQP3 and human AQP7 by molecular docking analysis. To explain these results, an antioxidant mechanism for the isolated compounds was proposed through blocking H2O2 passage mediated by aquaporin transport. On the other hand, 1, 2, and 3 were not cytotoxic in a panel of three cancer cell lines.

A Metric Based on the Efficient Determination Criterion.

This paper extends the concept of metrics based on the Bayesian information criterion (BIC), to achieve strongly consistent estimation of partition Markov models (PMMs). We introduce a set of metrics drawn from the family of model selection criteria known as efficient determination criteria (EDC). This generalization extends the range of options available in BIC for penalizing the number of model parameters. We formally specify the relationship that determines how EDC works when selecting a model based on a threshold associated with the metric. Furthermore, we improve the penalty options within EDC, identifying the penalty ln(ln(n)) as a viable choice that maintains the strongly consistent estimation of a PMM. To demonstrate the utility of these new metrics, we apply them to the modeling of three DNA sequences of dengue virus type 3, endemic in Brazil in 2023.

A pharmacist-led interprofessional medication adherence program improved adherence to oral anticancer therapies: The OpTAT randomized controlled trial.

BACKGROUND: Oral anticancer therapies such as protein kinase inhibitors (PKIs) are increasingly prescribed in cancer care. We aimed to evaluate the impact of a pharmacist-led interprofessional medication adherence program (IMAP) on patient implementation (dosing history), persistence (time until premature cessation of the treatment) and adherence to 27 PKIs prescribed for various solid cancers, as well as the impact on patients' beliefs about medicines (BAM) and quality of life (QoL). METHODS: Patients (n = 118) were randomized 1:1 into two arms. In the intervention arm, pharmacists supported patient adherence through monthly electronic and motivational feedback, including educational, behavioral and affective components, for 12 months. The control arm received standard care plus EM without intervention. All PKIs were delivered in electronic monitors (EMs). Medication implementation and adherence were compared between groups using generalized estimating equation models, in which relevant covariables were included; persistence was compared with Kaplan‒Meier curves. Information on all treatment interruptions was compiled for the analysis. Questionnaires to evaluate BAM and QoL were completed among patients who refused and those who accepted to participate at inclusion, 6 and 12 months post-inclusion or at study exit. RESULTS: Day-by-day PKI implementation was consistently higher and statistically significant in the intervention arm (n = 58) than in the control arm (n = 60), with 98.1% and 95.0% (Δ3.1%, 95% confidence interval (CI) of the difference 2.5%; 3.7%) implementation at 6 months, respectively. The probabilities of persistence and adherence were not different between groups, and no difference was found between groups for BAM and QoL scores. No difference in BAM or QoL was found among patients who refused versus those who participated. The intervention benefited mostly men (at 6 months, Δ4.7%, 95% CI 3.4%; 6.0%), those younger than 60 years (Δ4.0%, 95% CI 3.1%; 4.9%), those who had initiated PKI more than 60 days ago before inclusion (Δ4.5%, 95% CI 3.6%; 5.4%), patients without metastasis (Δ4.5%, 95% CI 3.4%; 5.7%), those who were diagnosed with metastasis more than 2 years ago (Δ5.3%, 95% CI 4.3%; 6.4%) and those who had never used any adherence tool before inclusion (Δ3.8%, 95% CI 3.1%; 4.5%). CONCLUSIONS: The IMAP, led by pharmacists in the context of an interprofessional collaborative practice, supported adherence, specifically implementation, to PKIs among patients with solid cancers. To manage adverse drug events, PKI transient interruptions are often mandated as part of a strategy for treatment and adherence optimization according to guidelines. Implementation of longer-term medication adherence interventions in the daily clinic may contribute to the improvement of progression-free survival. TRIAL REGISTRATION: ClinicalTrials.gov NCT04484064.

Risk assessment tools for bleeding in patients with unprovoked venous thromboembolism: an analysis of the PLATO-VTE study.

BACKGROUND: Guidelines suggest indefinite anticoagulation after unprovoked venous thromboembolism (VTE) unless the bleeding risk is high, yet there is no consistent guidance on assessing bleeding risk. OBJECTIVES: This study aimed to evaluate the performance of 5 bleeding risk tools (RIETE, VTE-BLEED, CHAP, VTE-PREDICT, and ABC-Bleeding). METHODS: PLATO-VTE, a prospective cohort study, included patients aged ≥40 years with a first unprovoked VTE. Risk estimates were calculated at VTE diagnosis and after 3 months of treatment. Primary outcome was clinically relevant bleeding, as per International Society on Thrombosis and Haemostasis criteria, during 24-month follow-up. Discrimination was assessed by the area under the receiver operating characteristic curve (AUROC). Patients were classified as having a "high risk" and "non-high risk" of bleeding according to predefined thresholds; bleeding risk in both groups was compared by hazard ratios (HRs). RESULTS: Of 514 patients, 38 (7.4%) had an on-treatment bleeding. AUROCs were 0.58 (95% CI, 0.48-0.68) for ABC-Bleeding, 0.56 (95% CI, 0.46-0.66) for RIETE, 0.53 (95% CI, 0.43-0.64) for CHAP, 0.50 (95% CI, 0.41-0.59) for VTE-BLEED, and 0.50 (95% CI, 0.40-0.60) for VTE-PREDICT. The proportion of high-risk patients ranged from 1.4% with RIETE to 36.9% with VTE-BLEED. The bleeding incidence in the high-risk groups ranged from 0% with RIETE to 13.0% with ABC-Bleeding, and in the non-high-risk groups, it varied from 7.7% with ABC-Bleeding to 9.6% with RIETE. HRs ranged from 0.93 (95% CI, 0.46-1.9) for VTE-BLEED to 1.67 (95% CI, 0.86-3.2) for ABC-Bleeding. Recalibration at 3-month follow-up did not alter the results. CONCLUSION: In this cohort, discrimination of currently available bleeding risk tools was poor. These data do not support their use in patients with unprovoked VTE.

New dockside eDNA based protocol to detect the seaweed Asparagopsis armata evaluated by stakeholders.

Early detection of invasive species is crucial to deal effectively with biological invasions in ports, which are hotspots of species introductions. In this study, a simplified end-time PCR methodology conducted on eDNA from water samples was developed for rapid detection of the invasive seaweed Asparagopsis armata (four hours from water collection to result visualization). It was tested dockside in four international Spanish ports in presence of stakeholders, whose feedback was obtained to explore the real applicability of this biotechnology. Although biological invasions were not a main concern for them, results indicate a unanimous approval of the methodology by the stakeholders, having detected the presence of A. armata in three of the ports. Stakeholders suggested further developments for easier application of the tool and multiple species detection, to be adopted for the control of invasive species in ports.

Occult cancer in patients with unprovoked venous thromboembolism: A nested case-control study.

OBJECTIVES: Detecting occult cancer in patients with unprovoked venous thromboembolism (VTE) remains a significant challenge. Our objective was to investigate the potential predictive role of coagulation-related biomarkers in the diagnosis of occult malignancies. METHODS: We conducted a nested case-control study with a 1-year prospective cohort of 214 patients with unprovoked VTE, with a focus on identifying occult cancer. At the time of VTE diagnosis, we measured various biomarkers, including soluble P-selectin (sP-selectin), dimerized plasmin fragment D (D-dimer), platelets, leukocytes, hemoglobin, total extracellular vesicles (EVs), EVs expressing tissue factor on their surface (TF+EVs), and EVs expressing P-selectin on their surface (Psel+EVs) in all participants. RESULTS: We observed statistically significant increased levels of sP-selectin (P = .015) in patients with occult cancer. Despite an increase in Psel+EVs, TF+EVs, D-dimer, and platelets within this group, however, no significant differences were found. When sP-selectin exceeded 62 ng/mL and D-dimer surpassed 10,000 µg/L, the diagnosis of occult cancer demonstrated a specificity of up to 91% (95% CI, 79.9%-96.7%). CONCLUSIONS: The combination of sP-selectin and D-dimer can be a valuable biomarker in detecting occult cancer in patients with unprovoked VTE. Further research is necessary to ascertain whether easily measurable biomarkers such as sP-selectin and D-dimer can effectively distinguish between patients who have VTE with and without hidden malignancies.

Proteomic analysis identifies HSP90AA1, PTK2B, and ANXA2 in the human entorhinal cortex in Alzheimer's disease: Potential role in synaptic homeostasis and Aß pathology through microglial and astroglial cells.

Alzheimer's disease (AD), the most prevalent neurodegenerative disorder worldwide, is clinically characterized by cognitive deficits. Neuropathologically, AD brains accumulate deposits of amyloid-ß (Aß) and tau proteins. Furthermore, these misfolded proteins can propagate from cell to cell in a prion-like manner and induce native proteins to become pathological. The entorhinal cortex (EC) is among the earliest areas affected by tau accumulation along with volume reduction and neurodegeneration. Neuron-glia interactions have recently come into focus; however, the role of microglia and astroglia in the pathogenesis of AD remains unclear. Proteomic approaches allow the determination of changes in the proteome to better understand the pathology underlying AD. Bioinformatic analysis of proteomic data was performed to compare ECs from AD and non-AD human brain tissue. To validate the proteomic results, western blot, immunofluorescence, and confocal studies were carried out. The findings revealed that the most disturbed signaling pathway was synaptogenesis. Because of their involvement in synapse function, relationship with Aß and tau proteins and interactions in the pathway analysis, three proteins were selected for in-depth study: HSP90AA1, PTK2B, and ANXA2. All these proteins showed colocalization with neurons and/or astroglia and microglia and with pathological Aß and tau proteins. In particular, ANXA2, which is overexpressed in AD, colocalized with amoeboid microglial cells and Aß plaques surrounded by astrocytes. Taken together, the evidence suggests that unbalanced expression of HSP90AA1, PTK2B, and ANXA2 may play a significant role in synaptic homeostasis and Aß pathology through microglial and astroglial cells in the human EC in AD.

Investigating the Relationship Between Marital Status and Ethnicity on Neurocognitive Functioning in a Rural Older Population: A Project FRONTIER Study.

OBJECTIVES: Research indicates being married is related to better physical and psychological health. Little is known regarding the relationship between marital status and neurocognitive functioning and whether it differs based on ethnicity (Hispanic vs non-Hispanic). This is the first study to examine this relationship in a sample of aging adults in rural Texas. METHODS: Data from 1,864 participants (Mage = 59.68, standard deviation [SD]age = 12.21), who were mostly Hispanic (n = 1,053), women (n = 1,295), and married (n = 1,125) from Project Facing Rural Obstacles to Healthcare Now Through Intervention, Education, & Research were analyzed. Neuropsychological testing comprised Repeatable Battery for the Assessment of Neuropsychological Status, Trails Making Test, and Clock Drawing. Participants were dichotomized, married, and unmarried. RESULTS: There was a significant interaction between Hispanic identity and marital status on overall neurocognitive functioning (F(1, 1,480) = 4.79, p < .05, ηp2 = 0.003). For non-Hispanic individuals, married individuals had higher overall neurocognitive functioning compared to unmarried individuals, whereas neurocognitive functioning for Hispanic individuals did not significantly differ between married and unmarried individuals. There were significant main effects as married individuals (M = 84.95, SD = 15.56) had greater overall neurocognitive functioning than unmarried individuals (M = 83.47, SD = 15.86; F(1, 1,480) = 14.67, p < .001, ηp2 = 0.01), Hispanic individuals (M = 78.02, SD = 14.25) had lower overall neurocognitive functioning than non-Hispanic individuals (M = 91.43, SD = 15.07; F(1, 1,480) = 284.99, p < .001, ηp2 = 0.16). DISCUSSION: Hispanics living in rural areas experience additional stressors that could lead to worse neurocognitive functioning, which is supported by the Lifespan Biopsychosocial Model of Cumulative Vulnerability and Minority Health, which postulates that race/ethnicity/socioeconomic-status-related stressors exacerbate the impact of other life stressors. Reduction of stress on rural Hispanics should be a priority as it could positively affect their neurocognitive functioning.

Ligand-Based Drug Design of Genipin Derivatives with Cytotoxic Activity against HeLa Cell Line: A Structural and Theoretical Study.

Cervical cancer is a malignant neoplastic disease, mainly associated to HPV infection, with high mortality rates. Among natural products, iridoids have shown different biological activities, including cytotoxic and antitumor effects, in different cancer cell types. Geniposide and its aglycone Genipin have been assessed against different types of cancer. In this work, both iridoids were evaluated against HeLa and three different cervical cancer cell lines. Furthermore, we performed a SAR analysis incorporating 13 iridoids with a high structural similarity to Geniposide and Genipin, also tested in the HeLa cell line and at the same treatment time. Derived from this analysis, we found that the dipole moment (magnitude and direction) is key for their cytotoxic activity in the HeLa cell line. Then, we proceeded to the ligand-based design of new Genipin derivatives through a QSAR model (R2 = 87.95 and Q2 = 62.33) that incorporates different quantum mechanic molecular descriptor types (ρ, ΔPSA, ∆Polarizability2, and logS). Derived from the ligand-based design, we observed that the presence of an aldehyde or a hydroxymethyl in C4, hydroxyls in C1, C6, and C8, and the lack of the double bond in C7-C8 increased the predicted biological activity of the iridoids. Finally, ten simple iridoids (D9, D107, D35, D36, D55, D56, D58, D60, D61, and D62) are proposed as potential cytotoxic agents against the HeLa cell line based on their predicted IC50 value and electrostatic features.

Update of the recommendations on the management of the SARS-CoV-2 coronavirus pandemic (COVID-19) in kidney transplant patients.

SARS-CoV-2 infection (COVID-19) has had a significant impact on transplant activity in our country. Mortality and the risk of complications associated with COVID-19 in kidney transplant recipients (KT) were expected to be higher due to their immunosuppressed condition and the frequent associated comorbidities. Since the beginning of the pandemic in March 2020 we have rapidly improved our knowledge about the epidemiology, clinical features and management of COVID-19 post-transplant, resulting in a better prognosis for our patients. KT units have been able to adapt their programs to this new reality, normalizing both donation and transplantation activity in our country. This manuscript presents a proposal to update the general recommendations for the prevention and treatment of infection in this highly vulnerable population such as KT.

Results of Kidney Transplantation with Controlled Cardiac Death Donors Older Than 70 Years.

BACKGROUND: The persistent shortage of optimal kidney donors and the progressive increase in patients on the waiting list has led to an expansion of organ acceptance criteria, such as controlled donation after circulatory death (cDCD) donors, as well as an expansion of criteria for accepting these organs (age, comorbidities, etc). However, there are some concerns and doubts about the survival outcomes achieved with these allografts. METHODS: A retrospective observational single-center study including all kidney transplants (KTs) from donors ≥70 years old using cDCD and donation after brain death (DBD) performed from January 2017 to December 2022. A comparative analysis was conducted between the 2 groups regarding clinical characteristics, medium and short-term clinical outcomes, and patient and graft survival rates. RESULTS: We studied 123 KTs performed with donors ≥70 years old, 81 from DBD, and 42 from cDCD. The median follow-up was 41 months (18-60). The age of the recipients from cDCD was higher (68 vs 65 years; P = .03), without significant differences in associated comorbidities. The age of DBD was significantly higher (73 vs 71; P = .001), and cDCD donors had a higher prevalence of diabetes (16% vs 5%; P = .04); however, there were no significant differences in Kidney Donor Profile Index between the groups. There was a trend toward a higher percentage of Delayed Graft Function in the cDCD group, although renal function was similar between the groups during follow-up. There were also no differences between the percentages of acute rejection. The mean graft survival rate censored for death with a functioning graft at one year (81% for DBD vs 79% for cDCD) and at 3 years (83% for DBD vs 75% for cDCD) was satisfactory (P = .141). CONCLUSIONS: The medium-term results of KT with cDCD donors are promising and comparable to those of DBD, allowing for an expansion of the donor pool for selected transplant recipients.

Synaptic Involvement of the Human Amygdala in Parkinson's Disease.

α-Synuclein, a protein mostly present in presynaptic terminals, accumulates neuropathologically in Parkinson's disease in a 6-stage sequence and propagates in the nervous system in a prion-like manner through neurons and glia. In stage 3, the substantia nigra are affected, provoking motor symptoms and the amygdaloid complex, leading to different nonmotor symptoms; from here, synucleinopathy spreads to the temporal cortex and beyond. The expected increase in Parkinson's disease incidence accelerates the need for detection biomarkers; however, the heterogeneity of this disease, including pathological aggregates and pathophysiological pathways, poses a challenge in the search for new therapeutic targets and biomarkers. Proteomic analyses are lacking, and the literature regarding synucleinopathy, neural and glial involvement, and volume of the human amygdaloid complex is controversial. Therefore, the present study combines both proteomic and stereological probes. Data-independent acquisition-parallel accumulation of serial fragmentation proteomic analysis revealed a remarkable proteomic impact, especially at the synaptic level in the human amygdaloid complex in Parkinson's disease. Among the 199 differentially expressed proteins, guanine nucleotide-binding protein G(i) subunit alpha-1 (GNAI1), elongation factor 1-alpha 1 (EEF1A1), myelin proteolipid protein (PLP1), neuroplastin (NPTN), 14-3-3 protein eta (YWHAH), gene associated with retinoic and interferon-induced mortality 19 protein (GRIM19), and orosomucoid-2 (ORM2) stand out as potential biomarkers in Parkinson's disease. Stereological analysis, however, did not reveal alterations regarding synucleinopathy, neural or glial populations, or volume changes. To our knowledge, this is the first proteomic study of the human amygdaloid complex in Parkinson's disease, and it identified possible biomarkers of the disease. Lewy pathology could not be sufficient to cause neurodegeneration or alteration of microglial and astroglial populations in the human amygdaloid complex in Parkinson's disease. Nevertheless, damage at the proteomic level is manifest, showing up significant synaptic involvement.

Testing a Model of Care for Patients on Immune Checkpoint Inhibitors Based on Electronic Patient-Reported Outcomes: Protocol for a Randomized Phase II Controlled Trial.

BACKGROUND: Management of severe symptomatic immune-related adverse events (IrAEs) related to immune checkpoint inhibitors (ICIs) can be facilitated by timely detection. As patients face a heterogeneous set of symptoms outside the clinical setting, remotely monitoring and assessing symptoms by using patient-reported outcomes (PROs) may result in shorter delays between symptom onset and clinician detection. OBJECTIVE: We assess the effect of a model of care for remote patient monitoring and symptom management based on PRO data on the time to detection of symptomatic IrAEs from symptom onset. The secondary objectives are to assess its effects on the time between symptomatic IrAE detection and intervention, IrAE grade (severity), health-related quality of life, self-efficacy, and overall survival at 6 months. METHODS: For this study, 198 patients with cancer receiving systemic treatment comprising ICIs exclusively will be recruited from 2 Swiss university hospitals. Patients are randomized (1:1) to a digital model of care (intervention) or usual care (control group). Patients are enrolled for 6 months, and they use an electronic app to complete weekly Functional Assessment of Cancer Therapy-General questionnaire and PROMIS (PROs Measurement Information System) Self-Efficacy to Manage Symptoms questionnaires. The intervention patient group completes a standard set of 37 items in a weekly PROs version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) questionnaire, and active symptoms are reassessed daily for the first 3 months by using a modified 24-hour recall period. Patients can add items from the full PRO-CTCAE item library to their questionnaire. Nurses call patients in the event of new or worsening symptoms and manage them by using a standardized triage algorithm based on the United Kingdom Oncology Nursing Society 24-hour triage tool. This algorithm provides guidance on deciding if patients should receive in-person care, if monitoring should be increased, or if self-management education should be reinforced. RESULTS: The Institut Suisse de Recherche Expérimentale sur le Cancer Foundation and Kaiku Health Ltd funded this study. Active recruitment began since November 2021 and is projected to conclude in November 2023. Trial results are expected to be published in the first quarter of 2024 and will be disseminated through publications submitted at international scientific conferences. CONCLUSIONS: This trial is among the first trials to use PRO data to directly influence routine care of patients treated with ICIs and addresses some limitations in previous studies. This trial collects a wider spectrum of self-reported symptom data daily. There are some methodological limitations brought by changes in evolving treatment standards for patients with cancer. This trial's results could entail further academic discussions on the challenges of diagnosing and managing symptoms associated with treatment remotely by providing further insights into the burden symptoms represent to patients and highlight the complexity of care procedures involved in managing symptomatic IrAEs. TRIAL REGISTRATION: ClinicalTrials.gov NCT05530187; https://www.clinicaltrials.gov/study/NCT05530187. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/48386.

Importance of Frailty in Kidney Transplant Recipients.

BACKGROUND: Frailty is a persistent chronic inflammatory syndrome present in many patients with chronic kidney disease. After kidney transplant (KT), it has been associated with complications such as delayed graft function, hospital readmission, or poorer KT survival. PURPOSE: To assess the impact of frailty on the results of KT. METHODS: Longitudinal prospective study of 65 patients included on the waiting list (WL) between October 2019 and October 2021. We used the FRAIL scale and recorded clinical characteristics, including demographic, dependency scales, and analytical parameters at the moment of the inclusion on the WL and at months 3 and 12 after KT. RESULTS: The mean age was 58 years old, and 70% of KT were men. The comorbidity burden was 26% diabetes, 83% hypertension, and 12% ischemic heart disease. Forty patients (61.5%) presented ≥1 point on the FRAIL scale, and 25 (38.4%) were robust. Frail patients (FRAIL score≥3) had a higher Charlson comorbidity index at the time of KT, a lower Barthel index, and a lower quality of life measured by KDQOL-36. No significant differences were observed in other variables, such as days of admission, surgical complications, or delayed graft function. There were 3 graft losses censored for death and 4 deaths, all in frail or prefrail patients. These patients had lower graft survival (P = .164) and patient survival (P = .096). At 12 months post KT, frailty improved in 67% of patients evaluated. CONCLUSION: Frailty is a common condition among patients on the WL, leading to poorer quality of life, greater dependency, and a higher risk of graft loss and mortality. Frailty conditions can be reversed in many patients after KT.

Management of immunosuppressive therapy in kidney transplant recipients with COVID-19. A multicentre national study derived from the Spanish Society of Nephrology COVID registry.

INTRODUCTION: SARS CoV2 infection has had a major impact on renal transplant patients with a high mortality in the first months of the pandemic. Intentional reduction of immunosuppressive therapy has been postulated as one of the cornerstone in the management of the infection in the absence of targeted antiviral treatment. This has been modified according to the patient`s clinical situation and its effect on renal function or anti-HLA antibodies in the medium term has not been evaluated. OBJECTIVES: Evaluate the management of immunosuppressive therapy made during SARS-CoV2 infection, as well as renal function and anti-HLA antibodies in kidney transplant patients 6 months after COVID19 diagnosis. MATERIAL AND METHODS: Retrospective, national multicentre, retrospective study (30 centres) of kidney transplant recipients with COVID19 from 01/02/20 to 31/12/20. Clinical variables were collected from medical records and included in an anonymised database. SPSS statistical software was used for data analysis. RESULTS: renal transplant recipients with COVID19 were included (62.6% male), with a mean age of 57.5 years. The predominant immunosuppressive treatment prior to COVID19 was triple therapy with prednisone, tacrolimus and mycophenolic acid (54.6%) followed by m-TOR inhibitor regimens (18.6%). After diagnosis of infection, mycophenolic acid was discontinued in 73.8% of patients, m-TOR inhibitor in 41.4%, tacrolimus in 10.5% and cyclosporin A in 10%. In turn, 26.9% received dexamethasone and 50.9% were started on or had their baseline prednisone dose increased. Mean creatinine before diagnosis of COVID19, at diagnosis and at 6 months was: 1.7 ±â€¯0.8, 2.1 ±â€¯1.2 and 1.8 ±â€¯1 mg/dl respectively (p < 0.001). 56.9% of the patients (N = 350) were monitored for anti-HLA antibodies. 94% (N = 329) had no anti-HLA changes, while 6% (N = 21) had positive anti-HLA antibodies. Among the patients with donor-specific antibodies post-COVID19 (N = 9), 7 patients (3.1%) had one immunosuppressant discontinued (5 patients had mycophenolic acid and 2 had tacrolimus), 1 patient had both immunosuppressants discontinued (3.4%) and 1 patient had no change in immunosuppression (1.1%), these differences were not significant. CONCLUSIONS: The management of immunosuppressive therapy after diagnosis of COVID19 was primarily based on discontinuation of mycophenolic acid with very discrete reductions or discontinuations of calcineurin inhibitors. This immunosuppression management did not influence renal function or changes in anti-HLA antibodies 6 months after diagnosis.

Time-Dependent Changes of Klotho and FGF-23 Levels after Kidney Transplantation: Role of Cold Ischemia Time, Renal Function and Graft Inflammation.

We investigated the evolution of serum klotho (s-Kl) and FGF-23 during the first two years post-kidney transplantation (KT), considering the cold ischemia time (CIT), glomerular filtration rate (GFR) and graft subclinical inflammation (SCI). We undertook a prospective, cohort, multicenter study of consecutive patients between April 2018 and January 2021 (with follow-up at 24 months). Subgroups were analyzed according to the median CIT (<14 vs. ≥14 h), the median GFR (≤40 vs. >40 mL/min/1.73 m2) and the presence of SCI at month 3. A total of 147 patients were included. s-Kl and fibroblast growth factor-23 (FGF-23) levels were measured at baseline and at months 3, 12 and 24. Graft biopsies (n = 96) were performed at month 3. All patients had low s-Kl levels at month 3. Patients with CIT < 14 h exhibited a significant increase in s-Kl at month 24. In patients with CIT ≥ 14 h, s-Kl at month 3 fell and lower s-Kl levels were seen at month 24. Patients with a GFR > 40 had a lesser decrease in s-Kl at month 3. FGF-23 fell significantly at months 3 and 12 in both GFR groups, a reduction maintained during follow-up. There were significant inter-group differences in s-Kl from months 3 to 24. CIT, GFR at 3 months and SCI were significantly associated with s-KI at month 3. A reduction in s-Kl at month 3 post-KT could be explained by longer CIT and delayed graft function as well as by impaired graft function. Early SCI may regulate s-Kl increase post-KT.

Formononetin, a Beer Polyphenol with Catabolic Effects on Chondrocytes.

Beer consumption has been identified as a risk factor for osteoarthritis (OA), a rheumatic disease characterised by cartilage degradation, joint inflammation, and eventual joint failure. One of the main isoflavonoids in beer is formononetin (FNT), an estrogenic compound also found in multiple plants and herbs. In this study, we aimed to investigate the effect of FNT on chondrocyte viability, inflammation, and metabolism. Cells were treated with FNT with or without IL-1ß for 48 h and during 7 days of differentiation. Cell viability was determined via MTT assay. Nitrite accumulation was determined by Griess reaction. The expression of genes involved in inflammation and metabolism was determined by RT-PCR. The results revealed that a low concentration of FNT had no deleterious effect on cell viability and decreased the expression of inflammation-related genes. However, our results suggest that FNT overexposure negatively impacts on chondrocytes by promoting catabolic responses. Finally, these effects were not mediated by estrogen receptors (ERs) or aryl hydrocarbon receptor (AhR). In conclusion, factors that favour FNT accumulation, such as long exposure times or metabolic disorders, can promote chondrocyte catabolism. These data may partially explain why beer consumption increases the risk of OA.

Development of an eHealth-enhanced model of care for the monitoring and management of immune-related adverse events in patients treated with immune checkpoint inhibitors.

PURPOSE: The use of electronic patient-reported outcome (ePRO) data in routine care has been tied to direct patient benefits such as improved quality of care and symptom control and even overall survival. The modes of action behind such benefits are seldom described in detail. Here, we describe the development of a model of care leveraging ePRO data to monitor and manage symptoms of patients treated with immune checkpoint inhibitors. METHODS: Development was split into four stages: (1) identification of an underlying theoretical framework, (2) the selection of an ePRO measure (ePROM), (3) the adaptation of an electronic application to collect ePRO data, and (4) the description of an ePRO-oriented workflow. The model of care is currently evaluated in a bicentric longitudinal randomized controlled phase II trial, the IePRO study. RESULTS: The IePRO model of care is grounded in the eHealth Enhanced Chronic Care Model. Patients are prompted to report symptoms using an electronic mobile application. Triage nurses are alerted, review the reported symptoms, and contact patients in case of a new or worsening symptom. Nurses use the UKONS 24-hour telephone triage tool to issue patient management recommendations to the oncology team. Adapted care coordinating procedures facilitate team collaboration and provide patients with timely feedback. CONCLUSION: This report clarifies how components of care are created and modified to leverage ePRO to enhance care. The model describes a workflow that enables care teams to be proactive and provide patients with timely, multidisciplinary support to manage symptoms.