The safety of a low protein diet in older adults with advanced chronic kidney disease.

BACKGROUND: A low protein diet (LPD) is recommended to patients with advanced chronic kidney disease (CKD), whereas geriatric guidelines recommend a higher amount of protein. The aim of this study was to evaluate the safety of LPD treatment in older adults with advanced CKD. METHODS: The EQUAL study is a prospective, observational study, including patients ≥65 years, incident estimated glomerular filtration rate <20 ml/min/1.73m², in six European countries with follow-up up till six years. Nutritional status was assessed by 7-point subjective global assessment (SGA) every 3-6 months. Prescribed diet (gram protein/kilogram/bodyweight) was recorded on every study visit; measured protein intake was available in three countries. Time to death and decline in nutritional status (SGA decrease by ≥2 points) were analysed using marginal structural models with dynamic inverse probability of treatment and censoring weights. RESULTS: Out of 1738 adults (631 prescribed LPD at any point during follow-up) there were 1319 with repeated SGA measurements of which 267 (20%) declined in SGA ≥ 2 points and 565 (32.5%) died. There was no difference in survival or decline in nutritional status for patients prescribed LPD ≤0.8 g/kg ideal bodyweight (Odds Ratio (OR) for mortality 1.15 (95% Confidence interval (CI) 0.86-1.55) and OR for decline in SGA 1.11 (95% CI 0.74-1.66) in the adjusted models. In patients prescribed LPD <0.6 g/kg ideal bodyweight, the results were similar. There was a significant interaction with LPD and higher age >75 years, lower SGA, and higher comorbidity burden for both mortality and nutritional status decline. CONCLUSIONS: In older adults with CKD approaching end-stage kidney disease, a traditional LPD prescribed and monitored according to routine clinical practice in Europe appears to be safe.

Case Report: CAR-T cells and subsequent maintenance with ponatinib in an adult Philadelphia acute lymphoblastic leukemia patient with hematological and extramedullary relapse after allogeneic stem cell transplantation.

Relapsed or refractory (r/r) Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) still represent an unmet clinical need despite the new immune therapies available for these patients. We report the case of a Ph + ALL relapsed one year after allogeneic stem cell transplant. After one DLI was started CAR-T program with brexucabtageneautoleucel, using as bridging treatment ponatinib, vincristine and prednisone. Brexu-cel infusion was performed in 2023, without CRS or ICANS onset. One month after Brexu-cel infusion BM aspirate and CT-PET showed recovery of full donor chimerism, MRD negativity and complete metabolic remission. Subsequently was started maintenance with ponatinib: at last follow-up, the patient persisted in leukemia-free status. CAR-T cells represent the most powerful treatment for r/r Ph + ALL but there is no consensus about the optimal bridging strategy and also regarding the management algorithm during "post CAR-T phase". Here, we report the efficacy of ponatinib as a bridge to anti-CD19 CAR-T cell therapy and as post CAR-T maintenance. Our experience suggests that a preserving approach with TKI associated to low-dose chemotherapy can be the optimal bridging therapy prior to CAR-T and that an "MRD-guided" and "TKI-based" maintenance strategy can represent the best choice for Ph + ALL which satisfactorily responds to CAR-T.

Effectiveness of biosimilar pegfilgrastim in patients with multiple myeloma after high-dose melphalan and autologous stem cell transplantation.

Multiple myeloma (MM) is the main indication for autologous stem cell transplantation (ASCT). Novel supportive therapies (e.g., granulocyte colony-stimulating factor) have significantly improved post-ASCT-related mortality; however, data on biosimilar pegfilgrastim-bmez (BIO/PEG) in this setting is lacking. This prospective cohort study compared Italian patients with MM who received BIO/PEG post-ASCT with data collected retrospectively from historical control groups from the same center who received either filgrastim-sndz (BIO/G-CSF) or pegfilgrastim (PEG; originator). The primary endpoint was time to neutrophil engraftment (three consecutive days with an absolute neutrophil count ≥ 0.5 × 109/L). Secondary endpoints included incidence and duration of febrile neutropenia (FN). Of the 231 patients included, 73 were treated with PEG, 102 with BIO/G-CSF, and 56 with BIO/PEG. Median age was 60 years and 57.1% were male. Neutrophil engraftment was reached after a median of 10 days in the BIO/PEG and PEG groups and 11 days in the BIO/G-CSF group. Among patients who achieved neutrophil engraftment earlier than this (i.e., day 9), 58% (29/50) were on PEG; of those who achieved it later (i.e., day 11), 80.8% (59/73) were on BIO/G-CSF. FN incidence was higher with BIO/G-CSF (61.4%) versus PEG (52.1%) or BIO/PEG (37.5%) (p = 0.02 among groups). Patients on BIO/PEG had less frequent grade 2-3 diarrhea (5.5%) compared with BIO/G-CSF (22.5%) or PEG (21.9%); grade 2-3 mucositis was most frequent in the BIO/G-CSF group. In conclusion, pegfilgrastim and its biosimilar displayed an advantageous efficacy and safety profile compared with biosimilar filgrastim in patients with MM post-ASCT.

Clinical and patient-reported trajectories at end-of-life in older patients with advanced CKD.

BACKGROUND: We explore longitudinal trajectories of clinical indicators, patient-reported outcomes, and hospitalizations, in the years preceding death in a population of older patients with advanced chronic kidney disease (CKD). METHODS: The EQUAL study is a European observational prospective cohort study with an incident eGFR <20 ml/min per 1.73 m2 and ≥65 years of age. The evolution of each clinical indicator was explored using generalized additive models during the 4 years preceding death. RESULTS: We included 661 decedents with a median time to death of 2.0 years (IQR 0.9-3.2). During the years preceding death, eGFR, Subjective Global Assessment score, and blood pressure declined, with accelerations seen at 6 months preceding death. Serum hemoglobin, hematocrit, cholesterol, calcium, albumin, and sodium values declined slowly during follow-up, with accelerations observed between 6 and 12 months preceding death. Physical and mental quality of life declined linearly throughout follow-up. The number of reported symptoms was stable up to 2 years prior to death, with an acceleration observed at 1 year prior to death. The rate of hospitalization was stable at around one hospitalization per person year, increasing exponentially at 6 months preceding death. CONCLUSIONS: We identified clinically relevant physiological accelerations in patient trajectories that began ∼6 to 12 months prior to death, which are likely multifactorial in nature, but correlate with a surge in hospitalizations. Further research should focus on how to effectively use this knowledge to inform patient and family expectations, to benefit the planning of (end-of-life) care, and to establish clinical alert systems.

Association between CKD-MBD and mortality in older patients with advanced CKD-results from the EQUAL study.

BACKGROUND: Chronic kidney disease-mineral and bone disorder (CKD-MBD) is a common complication of CKD; it is associated with higher mortality in dialysis patients, while its impact in non-dialysis patients remains mostly unknown. We investigated the associations between parathyroid hormone (PTH), phosphate and calcium (and their interactions), and all-cause, cardiovascular (CV) and non-CV mortality in older non-dialysis patients with advanced CKD. METHODS: We used data from the European Quality study, which includes patients aged ≥65 years with estimated glomerular filtration rate ≤20 mL/min/1.73 m2 from six European countries. Sequentially adjusted Cox models were used to assess the association between baseline and time-dependent CKD-MBD biomarkers and all-cause, CV and non-CV mortality. Effect modification between biomarkers was also assessed. RESULTS: In 1294 patients, the prevalence of CKD-MBD at baseline was 94%. Both PTH [adjusted hazard ratio (aHR) 1.12, 95% confidence interval (CI) 1.03-1.23, P = .01] and phosphate (aHR 1.35, 95% CI 1.00-1.84, P = .05), but not calcium (aHR 1.11, 95% CI 0.57-2.17, P = .76), were associated with all-cause mortality. Calcium was not independently associated with mortality, but modified the effect of phosphate, with the highest mortality risk found in patients with both hypercalcemia and hyperphosphatemia. PTH level was associated with CV mortality, but not with non-CV mortality, whereas phosphate was associated with both CV and non-CV mortality in most models. CONCLUSIONS: CKD-MBD is very common in older non-dialysis patients with advanced CKD. PTH and phosphate are independently associated with all-cause mortality in this population. While PTH level is only associated with CV mortality, phosphate seems to be associated with both CV and non-CV mortality.

The power of telemedicine to improve CAR-T cell therapy programs: lessons learned from COVID-19 pandemic.

PURPOSE: CAR-T programs will burden increasingly on healthcare systems, since the implementation of these therapies involves: multidisciplinary team collaboration, post-infusion hospitalization with risk of life-threatening toxicities, frequent in hospital visits and prolonged follow-up which heavily influence patients' quality of life. In this review we propose an innovative, telehealth-based, model for monitoring CAR-T patients: this method was used for managing a case of COVID-19 infection occurred two weeks after CAR-T cell infusion. METHODS: Several benefits for management of all these aspects of CAR-T programs could be made using telemedicine: for example, telemedicine real-time clinical monitoring could reduce the COVID-19 contagion risks for CAR-T patients. RESULTS: Our experience confirmed feasibility and utility of this approach in a real-life case. We believe that use of telemedicine for CAR-T patients could improve: the logistics of toxicity monitoring (frequent vital sign checks and neurologic assessments), the multidisciplinary team communication (patient selection, specialists consulting, coordination with pharmacists, etc.), the decrease in hospitalization time and the reduction of ambulatory visits. CONCLUSIONS: This approach will be fundamental for future CAR-T cell program development, enhancing patients' quality of life and cost-effectiveness for healthcare systems.

Do CAR-T and Allogeneic Stem Cell Transplant Both Have a Place in Lymphoid Neoplasms?

Allogeneic stem cell transplantation (allo-SCT) represented the first immunotherapy to treat hematologic malignancies: it has been considered as a cure for the disease and never as an approach to extend the life of patients. The success of allo-SCT derives both from the ability to treat patients with intensive chemoradiotherapy and from the potent graft-versus-leukemia effects mediated by donor immunity. Although considerable progress has been made in the last years, significant barriers still remain in the form of disease relapse, graft-versus-host disease, infectious complications, and regimen-related toxicities. Moreover, the treatment of hematologic malignancies, particularly acute lymphoblastic leukemia and certain forms of lymphomas, has been revolutionized by the commercial introduction of genetically modified autologous T-lymphocyte therapy (CAR-T). Our review discusses current standards and the shifting paradigms in the indications for allo-SCT and the role of CAR-T cell therapy for lymphoid neoplasms.

Converting from face-to-face to postal follow-up and its effects on participant retention, response rates and errors: lessons from the EQUAL study in the UK.

BACKGROUND: Prospective cohort studies are challenging to deliver, with one of the main difficulties lying in retention of participants. The need to socially distance during the COVID-19 pandemic has added to this challenge. The pre-COVID-19 adaptation of the European Quality (EQUAL) study in the UK to a remote form of follow-up for efficiency provides lessons for those who are considering changing their study design. METHODS: The EQUAL study is an international prospective cohort study of patients ≥65 years of age with advanced chronic kidney disease. Initially, patients were invited to complete a questionnaire (SF-36, Dialysis Symptom Index and Renal Treatment Satisfaction Questionnaire) at research clinics every 3-6 months, known as "traditional follow-up" (TFU). In 2018, all living patients were invited to switch to "efficient follow-up" (EFU), which used an abbreviated questionnaire consisting of SF-12 and Dialysis Symptom Index. These were administered centrally by post. Response rates were calculated using returned questionnaires as a proportion of surviving invitees, and error rates presented as the average percentage of unanswered questions or unclear answers, of total questions in returned questionnaires. Response and error rates were calculated 6-monthly in TFU to allow comparisons with EFU. RESULTS: Of the 504 patients initially recruited, 236 were still alive at the time of conversion to EFU; 111 of these (47%) consented to the change in follow-up. In those who consented, median TFU was 34 months, ranging from 0 to 42 months. Their response rates fell steadily from 88% (98/111) at month 0 of TFU, to 20% (3/15) at month 42. The response rate for the first EFU questionnaire was 60% (59/99) of those alive from TFU. With this improvement in response rates, the first EFU also lowered errors to baseline levels seen in early follow-up, after having almost trebled throughout traditional follow-up. CONCLUSIONS: Overall, this study demonstrates that administration of shorter follow-up questionnaires by post rather than in person does not negatively impact patient response or error rates. These results may be reassuring for researchers who are trying to limit face-to-face contact with patients during the COVID-19 pandemic.

Netupitant/palonosetron without dexamethasone for preventing nausea and vomiting in patients with multiple myeloma receiving high-dose melphalan for autologous stem cell transplantation: a single-center experience.

Chemotherapy-induced nausea and vomiting (CINV) is one of the most frequent adverse events compromising quality of life (QoL) in patients undergoing autologous stem cell transplantation (ASCT). However, CINV prophylaxis is still lacking uniformity for high-dose melphalan (HDM), which is used to condition patients with multiple myeloma (MM). Netupitant/palonosetron (NEPA) is administered with dexamethasone (DEXA) for CINV prevention in several chemotherapy regimens. Our study aims to assess the efficacy of NEPA, without DEXA, in preventing CINV in 106 adult patients with MM receiving HDM and ASCT. All patients had antiemetic prophylaxis with multiple doses of NEPA 1 h before the start of conditioning and after 72 h and 120 h. A complete response (CR) was observed in 99 (93%) patients at 120 h (overall phase). The percentage of patients with complete control was 93%. The CR rate during the acute phase was 94% (n = 100). During the delayed phase, the CR rate was 95% (n = 101). Grade 1 nausea and vomiting were experienced by 82% and 12% of the patients, respectively. Grade 2 nausea was reported in 18% and vomiting in 10% of patients. Our results showed, for the first time, that NEPA, without DEXA, was a well-tolerated and effective antiemetic option for MM patients receiving HDM followed by ASCT.

Patient-Reported Measures and Lifestyle Are Associated With Deterioration in Nutritional Status in CKD Stage 4-5: The EQUAL Cohort Study.

OBJECTIVE: The aim of this study was to explore the changes in nutritional status before dialysis initiation and to identify modifiable risk factors of nutritional status decline in older adults with advanced renal disease. DESIGN AND METHODS: The European Quality Study on treatment in advanced chronic kidney disease (EQUAL) is a prospective, observational cohort study involving six European countries. We included 1,103 adults >65 years with incident estimated glomerular filtration rate <20 mL/min/1.73 m2 not on dialysis, attending nephrology care. Nutritional status was assessed with the 7-point Subjective Global Assessment tool (7-p SGA), patient-reported outcomes with RAND-36 and the Dialysis Symptom Index. Logistic regression was used to estimate the associations between potential risk factors and SGA decline. RESULTS: The majority of the patients had a normal nutritional status at baseline, 28% were moderately malnourished (SGA ≤5). Overall, mean SGA decreased by -0.18 points/year, (95% confidence interval -0.21; -0.14). More than one-third of the study participants (34.9%) deteriorated in nutritional status (1 point decline in SGA) and 10.9% had a severe decline in SGA (≥2 points). The proportion of patients with low SGA (≤5) increased every 6 months. Those who dropped in SGA also declined in estimated glomerular filtration rate and mental health score. Every 10 points decrease in physical function score increased the odds of decline in SGA by 23%. Lower physical function score at baseline, gastrointestinal symptoms, and smoking were risk factors for impaired nutritional status. There was an interaction between diabetes and physical function on SGA decline. CONCLUSIONS: Nutritional status deteriorated in more than one-third of the study participants during the first year of follow-up. Lower patient-reported physical function, more gastrointestinal symptoms, and current smoking were associated with decline in nutritional status.

Kidney Failure Prediction Models: A Comprehensive External Validation Study in Patients with Advanced CKD.

BACKGROUND: Various prediction models have been developed to predict the risk of kidney failure in patients with CKD. However, guideline-recommended models have yet to be compared head to head, their validation in patients with advanced CKD is lacking, and most do not account for competing risks. METHODS: To externally validate 11 existing models of kidney failure, taking the competing risk of death into account, we included patients with advanced CKD from two large cohorts: the European Quality Study (EQUAL), an ongoing European prospective, multicenter cohort study of older patients with advanced CKD, and the Swedish Renal Registry (SRR), an ongoing registry of nephrology-referred patients with CKD in Sweden. The outcome of the models was kidney failure (defined as RRT-treated ESKD). We assessed model performance with discrimination and calibration. RESULTS: The study included 1580 patients from EQUAL and 13,489 patients from SRR. The average c statistic over the 11 validated models was 0.74 in EQUAL and 0.80 in SRR, compared with 0.89 in previous validations. Most models with longer prediction horizons overestimated the risk of kidney failure considerably. The 5-year Kidney Failure Risk Equation (KFRE) overpredicted risk by 10%-18%. The four- and eight-variable 2-year KFRE and the 4-year Grams model showed excellent calibration and good discrimination in both cohorts. CONCLUSIONS: Some existing models can accurately predict kidney failure in patients with advanced CKD. KFRE performed well for a shorter time frame (2 years), despite not accounting for competing events. Models predicting over a longer time frame (5 years) overestimated risk because of the competing risk of death. The Grams model, which accounts for the latter, is suitable for longer-term predictions (4 years).

International prescribing patterns and polypharmacy in older people with advanced chronic kidney disease: results from the European Quality study.

BACKGROUND: People with chronic kidney disease (CKD) are at high risk of polypharmacy. However, no previous study has investigated international prescribing patterns in this group. This article aims to examine prescribing and polypharmacy patterns among older people with advanced CKD across the countries involved in the European Quality (EQUAL) study. METHODS: The EQUAL study is an international prospective cohort study of patients ≥65 years of age with advanced CKD. Baseline demographic, clinical and medication data were analysed and reported descriptively. Polypharmacy was defined as ≥5 medications and hyperpolypharmacy as ≥10. Univariable and multivariable linear regressions were used to determine associations between country and the number of prescribed medications. Univariable and multivariable logistic regression were used to determine associations between country and hyperpolypharmacy. RESULTS: Of the 1317 participants from five European countries, 91% were experiencing polypharmacy and 43% were experiencing hyperpolypharmacy. Cardiovascular medications were the most prescribed medications (mean 3.5 per person). There were international differences in prescribing, with significantly greater hyperpolypharmacy in Germany {odds ratio (OR) 2.75 [95% confidence interval (CI) 1.73-4.37]; P < 0.001, reference group UK}, the Netherlands [OR 1.91 (95% CI 1.32-2.76); P = 0.001] and Italy [OR 1.57 (95% CI 1.15-2.15); P = 0.004]. People in Poland experienced the least hyperpolypharmacy [OR 0.39 (95% CI 0.17-0.87); P = 0.021]. CONCLUSIONS: Hyperpolypharmacy is common among older people with advanced CKD, with significant international differences in the number of medications prescribed. Practice variation may represent a lack of consensus regarding appropriate prescribing for this high-risk group for whom pharmacological treatment has great potential for harm as well as benefit.

Reducing salt intake by urine chloride self-measurement in non-compliant patients with chronic kidney disease followed in nephrology clinics: a randomized trial.

BACKGROUND: Adherence to low salt diets and control of hypertension remain unmet clinical needs in chronic kidney disease (CKD) patients. METHODS: We performed a 6-month multicentre randomized trial in non-compliant patients with CKD followed in nephrology clinics testing the effect of self-measurement of urinary chloride (69 patients) as compared with standard care (69 patients) on two primary outcome measures, adherence to a low sodium (Na) diet (<100 mmol/day) as measured by 24-h urine Na (UNa) excretion and 24-h ambulatory blood pressure (ABPM) monitoring. RESULTS: In the whole sample (N = 138), baseline UNa and 24-h ABPM were143 ± 64 mmol/24 h and 131 ± 18/72 ± 10 mmHg, respectively, and did not differ between the two study arms. Patients in the active arm of the trial used >80% of the chloride strips provided to them at the baseline visit and at follow-up visits. At the third month, UNa was 35 mmol/24 h (95% CI 10.8-58.8 mmol/24 h; P = 0.005) lower in the active arm than the control arm, whereas at 6 months the between-arms difference in UNa decreased and was no longer significant [23 mmol/24 h (95% CI -5.6-50.7); P = 0.11]. The 24-h ABPM changes as well as daytime and night-time BP changes at 3 and 6 months were similar in the two study arms (Month 3, P = 0.69-0.99; Month 6, P = 0.73-0.91). Office BP, the use of antihypertensive drugs, estimated Glomerular Filtration Rate (eGFR) and proteinuria remained unchanged across the trial. CONCLUSIONS: The application of self-measurement of urinary chloride to guide adherence to a low salt diet had a modest effect on 24-h UNa and no significant effect on 24-h ABPM.

Granisetron transdermal system and dexamethasone for the prevention of nausea and vomiting in multiple myeloma patients receiving chemo-mobilization: An observational real-world study of effectiveness and safety.

PURPOSE: Cyclophosphamide (CY) in a dose of 2-4 g/m2 is widely used for hemopoietic progenitor stem cells mobilization. CY administration is associated with several adverse effects, including chemotherapy-induced nausea and vomiting (CINV). This study aimed to evaluate the efficacy and tolerability of granisetron transdermal system (GTDS) plus dexamethasone in the management of CINV in MM patients undergoing chemo-mobilization with CY. METHODS: In this single-center, prospective, observational, real world study, GTDS plus dexamethasone was administered to MM patients receiving chemo-mobilization based on CY 2 g/m2 plus G-CSF in an outpatient setting. The rate of complete response was evaluated as the main outcome. Other outcomes were rate of complete control of CINV, incidence of nausea/vomiting of any grade and safety. RESULTS: A total of 88 patients were enrolled. A complete response was achieved in 45.5 % of patients; among them, 39.77 % attained complete control of CINV. Nausea and vomiting never occurred in 34.1 % and 45.5 % of patients, respectively. No episodes of grade 3-4 nausea and/or vomiting were documented. GTDS was safe and well tolerated. CONCLUSION: In real world, GTDS provided an innovative, effective, and well-tolerated control of CINV in MM patients after chemo-mobilization with CY. The study found out effectiveness of a non-invasive delivery system of antiemetic.

Long-term blood pressure monitoring by office and 24-h ambulatory blood pressure in renal transplant patients: a longitudinal study.

BACKGROUND: Renal transplant patients have a high prevalence of nocturnal hypertension, and hypertension misclassification by office blood pressure (BP) is quite common in these patients. The potential impact of hypertension misclassification by office BP on hypertension management in this population has never been analysed. METHODS: We performed a longitudinal study in a cohort of 260 clinically stable renal transplant patients. In all, 785 paired office and 24-h ambulatory blood pressure monitoring (24-hABPM) measurements over a median follow-up of 3.9 years were available in the whole cohort. RESULTS: A total of 74% of patients had nocturnal hypertension (>120/70 mmHg). Average office BP and 24-hABPM remained quite stable over follow-up, as did the prevalence of nocturnal hypertension, which was 77% at the last observation. However, the global agreement between office BP and average 24 h, daytime and night-time BP was unsatisfactory (k-statistics 0.10-0.26). In 193 visits (25% of all visits) where office BP indicated the need of antihypertensive therapy institution or modification (BP >140/90 mmHg), 24-hABPM was actually normal (<130/80 mmHg), while in 94 visits (12%), 24-hABPM was in the hypertensive range while office BP was normal. Overall, in 37% of visits, office BP provided misleading therapeutic indications. CONCLUSIONS: Hypertension misclassification by office BP is a common phenomenon in stable renal transplant patients on long-term follow-up. Office BP may lead to inappropriate therapeutic decisions in over one-third of follow-up visits in these patients.

Urine chloride self-measurement to monitor sodium chloride intake in patients with chronic kidney disease.

Background Excessive sodium intake is a risk factor for hypertension, cardiovascular disease and the risk for kidney failure in chronic kidney disease (CKD) patients. Methods We tested the diagnostic performance and the feasibility of an inexpensive method based on urine chloride strips for self-monitoring sodium intake in a series of 72 CKD patients. Results Twenty-four hour urinary chloride as measured by the reactive strips and 24 h urinary sodium were interrelated (r=0.59, p<0.001). Forty-nine out of 72 patients (78%) had a 24 h urinary sodium >100 mmol/24 h, i.e. the upper limit recommended by current CKD guidelines. The strip method had 75.5% sensitivity and 82.6% specificity to correctly classify patients with urine sodium >100 mmol/24 h. The positive and the negative predictive values were 90.2% and 61.3%, respectively. The overall accuracy (ROC curve analysis) of urine chloride self-measurement for the >100 mmol/24 h sodium threshold was 87% (95% CI: 77%-97%). The large majority of patients (97%) perceived the test as useful to help compliance with the prescribed dietary sodium and considered the test as simple and of immediate application (58%) or feasible but requiring attention (39%). Conclusions A simple and inexpensive test for urine chloride measurement has a fairly good performance for the diagnosis of excessive sodium intake. The test is feasible and it is perceived by CKD patients as helpful for enhancing compliance to the dietary sodium recommendations. The usefulness of this test for improving hypertension control in CKD patients will be tested in a clinical trial (Clinicaltrials.gov RF-2010-2314890).

Protein Biomarkers and Major Cardiovascular Events in Older People With Advanced CKD: The European Quality (EQUAL) Study.

Rationale & Objective: Cardiovascular disease is the leading cause of morbidity and mortality in chronic kidney disease (CKD). We investigated 184 inflammatory and cardiovascular proteins to determine their potential as biomarkers for major cardiovascular events (MACEs). Study Design: The European Quality (EQUAL) is an observational cohort study that enrolled people aged ≥65 years with an estimated glomerular filtration rate ≤20 mL/min/1.73 m2. Setting & Participants: Recruited participants were split into the discovery (n = 611) and replication cohorts (n = 292). Exposure: Levels of 184 blood proteins were measured at the baseline visit, and each protein was analyzed individually. Outcome: MACE. Analytical Approach: Cox proportional hazard models adjusted for age, sex, estimated glomerular filtration rate, previous MACE, and country were used to determine the risk of MACE. Proteins with false discovery rate adjusted P values of <0.05 in the discovery cohort were tested in the replication cohort. Sensitivity analyses were performed by adjusting for traditional risk factors, CKD-specific risk factors, and level of proteinuria and segregating atherosclerotic and nonatherosclerotic MACE. Results: During a median follow-up of 2.9 years, 349 people (39%) experienced a MACE. Forty-eight proteins were associated with MACE in the discovery cohort; 9 of these were reproduced in the replication cohort. Three of these proteins maintained a strong association with MACE after adjustment for traditional and CKD-specific risk factors and proteinuria. Tenascin (TNC), fibroblast growth factor-23 (FGF-23), and V-set and immunoglobulin domain-containing protein 2 (VSIG2) were associated with both atherosclerotic and nonatherosclerotic MACE. All replicated proteins except carbonic anhydrase 1 and carbonic anhydrase 3 were associated with nonatherosclerotic MACE. Limitations: Single protein concentration measurements and limited follow-up time. Conclusions: Our findings corroborate previously reported relationships between FGF-23, vascular cell adhesion protein-1, TNC, and placental growth factor with cardiovascular outcomes in CKD. We identify 5 proteins not previously linked with MACE in CKD that may be targets for future therapies. Plain-Language Summary: Kidney disease increases the risk of heart disease, stroke, and other vascular conditions. Blood tests that predict the likelihood of these problems may help to guide treatment, but studies are needed in people with kidney disease. We analyzed blood tests from older people with kidney disease, looking for proteins associated with higher risk of these conditions. Nine proteins were identified, of which 3 showed a strong effect after all other information was considered. This work supports previous research regarding 4 of these proteins and identifies 5 additional proteins that may be associated with higher risk. Further work is needed to confirm our findings and to determine whether these proteins can be used to guide treatment.

Integrating CAR-T cell therapy into the management of DLBCL: what we are learning.

INTRODUCTION: Chimeric Antigen Receptor ;(CAR) T cells therapies have become part of the standard of care for patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). The weakness of CAR-T therapies is that there are no comparative clinical trials, although many publications based on real-life data have confirmed the results obtained in pivotal studies. After several years of the commercialization of CAR-T, some points still need to be fully clarified. Healthcare professionals have questions about identifying patients who may benefit from therapy. There are aspects inherent in the accessibility of care related to improved relationships between CAR-T-delivering and referral centers. AREAS COVERED: Open questions are inherent in the salvage and bridge therapy, predictive criteria for response and persistence of CAR-T after infusion. Managing toxicities remain a top priority and one of the points on which further knowledge is needed. EXPERT OPINION: This review aims to describe the current landscape of CAR-T cells in DLBCL, outline their outcomes and toxicities, and explain the outstanding questions that remain to be addressed.

The Role of MicroRNA in Graft-Versus-Host-Disease: A Review.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a clinically challenging modality for the treatment of many hematologic diseases such as leukemia, lymphoma, and myeloma. Graft-versus-host disease (GVHD) is a common complication after allo-HSCT and remains a major cause of morbidity and mortality, limiting the success of a potentially curative transplant. Several microRNAs (miRNAs) have recently been shown to impact the biology of GVHD. They are molecular regulators involved in numerous processes during T-cell development, homeostasis, and activation, and contribute to the pathological function of T-cells during GvHD. Here, we review the key role of miRNAs contributing to the GvHD; their detection might be an interesting possibility in the early diagnosis and monitoring of disease.