The clinical characteristics, management, and outcome of coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) after solid organ transplant (SOT) ...remain unknown. We report our preliminary experience with 18 SOT (kidney 44.4%, liver 33.3%, and heart 22.2%) recipients diagnosed with COVID‐19 by March 23, 2020 at a tertiary‐care center at Madrid. Median age at diagnosis was 71.0 ± 12.8 years, and the median interval since transplantation was 9.3 years. Fever (83.3%) and radiographic abnormalities in form of unilateral or bilateral/multifocal consolidations (72.2%) were the most common presentations. Lopinavir/ritonavir (usually associated with hydroxychloroquine) was used in 50.0% of patients and had to be prematurely discontinued in 2 of them. Other antiviral regimens included hydroxychloroquine monotherapy (27.8%) and interferon‐β (16.7%). As of April 4, the case‐fatality rate was 27.8% (5/18). After a median follow‐up of 18 days from symptom onset, 30.8% (4/13) of survivors developed progressive respiratory failure, 7.7% (1/13) showed stable clinical condition or improvement, and 61.5% (8/13) had been discharged home. C‐reactive protein levels at various points were significantly higher among recipients who experienced unfavorable outcome. In conclusion, this frontline report suggests that SARS‐CoV‐2 infection has a severe course in SOT recipients.
In the present experience with 18 transplant recipients diagnosed with COVID‐19 by March 23, 2020 at their institution in Madrid, the authors found a case fatality rate of 27.8%, with 30.8% of survivors developing progressive respiratory failure or acute respiratory distress syndrome.
•Narrative review of machine learning methods used on end-stage kidney disease.•Techniques to predict survival in kidney transplantation and dialysis therapy.•Models used to analyze the incidence of ...infection or tacrolimus toxicity.•Algorithms used to analyze other dialysis variables to predict mortality.
In the field of medicine, decision-making has traditionally been carried out based on the best available scientific information and the experience of specialists using data found in analog formats such as radiographies, medical reports, and handwritten notes, among others. In this sense, the Big Data phenomenon is changing the world of medicine since the technologies that have been developed have made available to researchers and clinicians enormous amounts of data in digital formats that can be used to complement or help in complex tasks such as mentioned decision making. A key element in this process is data analysis techniques, since without them it is not possible to exploit the information. Currently the most used techniques are based on algorithms in the area of artificial intelligence and more specifically machine learning. This paper focuses on a specific domain of medicine, renal replacement therapies for end-stage renal disease, where machine learning is beginning to be used as a complementary tool to predict or make decisions. This paper provides a narrative review of the main machine learning methods that are being used to conduct end-stage renal disease treatment analyses.
The replication kinetics of nonpathogenic anelloviruses belonging to the Alphatorquevirus genus (such as torque teno virus) might reflect the overall state of posttransplant immunosuppression. We ...analyzed 221 kidney transplant (KT) recipients in whom plasma alphatorquevirus DNA load was quantified by real‐time polymerase chain reaction at baseline and regularly through the first 12 posttransplant months. Study outcomes included posttransplant infection and a composite of opportunistic infection and/or de novo malignancy (immunosuppression‐related adverse event iRAE). Alphatorquevirus DNA loads at month 1 were higher among patients who subsequently developed posttransplant infection (P = .023) or iRAE (P = .009). Likewise, those with iRAE beyond months 3 and 6 also exhibited higher peak viral loads over the preceding periods. Areas under the curve for log10 alphatorquevirus DNAemia estimated by months 1 or 6 were significantly higher in patients experiencing study outcomes. Alphatorquevirus DNA loads above 3.15 and 4.56 log10 copies/mL at month 1 predicted the occurrence of posttransplant infection (adjusted hazard ratio aHR: 2.88; 95% confidence interval CI: 1.13‐7.36; P = .027) and iRAE (aHR: 5.17; 95% CI: 2.01‐13.33; P = .001). In conclusion, posttransplant monitoring of plasma alphatorquevirus DNA kinetics may be useful to identify KT recipients at increased risk of immunosuppression‐related complications.
In this single‐center prospective cohort study, the kinetics of plasma alphatorquevirus (highly prevalent, nonpathogenic anelloviruses) DNA levels were found to be associated with the occurrence of overall infection and immunosuppression‐related adverse events in kidney transplant recipients, suggesting a potential role as a surrogate marker of the overall amount of posttransplant immunosuppression.
Immunizing human volunteers by mosquito bite with radiation-attenuated Plasmodium falciparum sporozoites (RAS) results in high-level protection against infection. Only two volunteers have been ...similarly immunized with P. vivax (Pv) RAS, and both were protected. A phase 2 controlled clinical trial was conducted to assess the safety and protective efficacy of PvRAS immunization.
A randomized, single-blinded trial was conducted. Duffy positive (Fy+; Pv susceptible) individuals were enrolled: 14 received bites from irradiated (150 ± 10 cGy) Pv-infected Anopheles mosquitoes (RAS) and 7 from non-irradiated non-infected mosquitoes (Ctl). An additional group of seven Fy- (Pv refractory) volunteers was immunized with bites from non-irradiated Pv-infected mosquitoes. A total of seven immunizations were carried out at mean intervals of nine weeks. Eight weeks after last immunization, a controlled human malaria infection (CHMI) with non-irradiated Pv-infected mosquitoes was performed. Nineteen volunteers completed seven immunizations (12 RAS, 2 Ctl, and 5 Fy-) and received a CHMI. Five of 12 (42%) RAS volunteers were protected (receiving a median of 434 infective bites) compared with 0/2 Ctl. None of the Fy- volunteers developed infection by the seventh immunization or after CHMI. All non-protected volunteers developed symptoms 8-13 days after CHMI with a mean pre-patent period of 12.8 days. No serious adverse events related to the immunizations were observed. Specific IgG1 anti-PvCS response was associated with protection.
Immunization with PvRAS was safe, immunogenic, and induced sterile immunity in 42% of the Fy+ volunteers. Moreover, Fy- volunteers were refractory to Pv malaria.
Identifier: NCT01082341.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
SARS‐CoV‐2 infection has produced high mortality in kidney transplant (KT) recipients, especially in the elderly. Until December 2020, 1011 KT with COVID‐19 have been prospectively included in the ...Spanish Registry and followed until recovery or death. In multivariable analysis, age, pneumonia, and KT performed ≤6 months before COVID‐19 were predictors of death, whereas gastrointestinal symptoms were protective. Survival analysis showed significant increasing mortality risk in four subgroups according to recipient age and time after KT (age <65 years and posttransplant time >6 months, age <65 and time ≤6, age ≥65 and time >6 and age ≥65 and time ≤6): mortality rates were, respectively, 11.3%, 24.5%, 35.4%, and 54.5% (p < .001). Patients were significantly younger, presented less pneumonia, and received less frequently specific anti‐COVID‐19 treatment in the second wave (July–December) than in the first one (March–June). Overall mortality was lower in the second wave (15.1 vs. 27.4%, p < .001) but similar in critical patients (66.7% vs. 58.1%, p = .29). The interaction between age and time post‐KT should be considered when selecting recipients for transplantation in the COVID‐19 pandemic. Advanced age and a recent KT should foster strict protective measures, including vaccination.
Older recipients diagnosed with COVID‐19 in the first 6 months after transplantation present the highest risk for a fatal outcome during the second wave of the COVID‐19 pandemic.
Monitoring for cytomegalovirus (CMV)‐specific cell‐mediated immunity (CMV‐CMI) may be useful for individualizing valganciclovir (VGCV) prophylaxis after kidney transplantation (KT). We performed a ...commercial ELISA‐based interferon (IFN)‐γ release assay (QTF‐CMV) from posttransplant months 2‐5 (362 points) in 120 CMV‐seropositive KT recipients that received antithymocyte globulin as induction therapy and VGCV prophylaxis (median of 92 days). Forty‐seven patients (39.3%) had CMV infection after discontinuation of prophylaxis. The QTF‐CMV assay was reactive, nonreactive, and indeterminate in 264 (72.9%), 90 (24.9%), and 8 points (2.2%). The QTF‐CMV assay at prophylaxis discontinuation exhibited suboptimal accuracy for predicting protective CMV‐CMI (sensitivity: 77.4%; specificity: 34.3%; positive predictive value PPV: 64.1%; negative predictive value NPV: 50.0%), with no differences in 1‐year CMV infection rates between patients with negative (nonreactive or indeterminate) or reactive results (45.8% vs 36.1%; P = .244). Specificity and PPV to predict protective CMV‐CMI improved by elevating the IFN‐γ cutoff value to 1.13 IU/mL (65.7% and 71.4%) and 7.0 IU/mL (85.7% and 76.2%), although NPVs decreased. The QTF‐CMV assay as per manufacturer's interpretative criteria performed poorly to predict protection from CMV infection following discontinuation of VGCV prophylaxis among ATG‐treated CMV‐seropositive KT recipients. This performance is slightly improved by modifying the IFN‐γ positivity threshold.
This study of CMV‐seropositive kidney transplant recipients who received induction therapy with antithymocyte globulin demonstrates that monitoring of cell‐mediated immunity with a commercial ELISA‐based interferon‐γ release assay performed poorly to predict protection from CMV infection following discontinuation of valganciclovir prophylaxis. See Kumar and Humar’s editorial on page 1961.
One of the main problems that affect patients in dialysis therapy who are on the waiting list to receive a kidney transplant is predicting their survival time if they do not receive a transplant. ...This paper proposes a new approach to survival prediction based on artificial intelligence techniques combined with statistical methods to study the association between sociodemographic factors and patient survival on the waiting list if they do not receive a kidney transplant. This new approach consists of a first stage that uses the clustering techniques that are best suited to the data structure (K-Means, Mini Batch K-Means, Agglomerative Clustering and K-Modes) used to identify the risk profile of dialysis patients. Later, a new method called False Clustering Discovery Reduction is performed to determine the minimum number of populations to be studied, and whose mortality risk is statistically differentiable. This approach was applied to the OPTN medical dataset (n = 44,663). The procedure started from 11 initial clusters obtained with the Agglomerative technique, and was reduced to eight final risk populations, for which their Kaplan-Meier survival curves were provided. With this result, it is possible to make predictions regarding the survival time of a new patient who enters the waiting list if the sociodemographic profile of the patient is known. To do so, the predictive algorithm XGBoost is used, which allows the cluster to which it belongs to be predicted and the corresponding Kaplan-Meier curve to be associated with it. This prediction process is achieved with an overall Multi-class AUC of 99.08 %.
•New approach to predicting survival time of patients waiting for kidney transplant•Flexible approach allowing new algorithms and statistical tests to be incorporated•Methodology to obtain minimum number of statistically differentiable clusters•Association between key sociodemographic factors and waiting list lifetime•Prediction of new patients' survival probabilities with Multi-class AUC of 99 %
Uncontrolled donation after circulatory death (uDCD) increases organ availability for kidney transplant (KT) with short‐term outcomes similar to those obtained from donation after brain death (DBD) ...donors. However, heterogeneous results in the long term have been reported. We compared 10‐year outcomes between 237 KT recipients from uDCD donors maintained by normothermic extracorporeal membrane oxygenation (nECMO) and 237 patients undergoing KT from standard criteria DBD donors during the same period at our institution. We further analyzed risk factors for death‐censored graft survival in the uDCD group. Delayed graft function (DGF) was more common in the uDCD group (73.4% vs 46.4%; P < .01), although glomerular filtration rates at the end of follow‐up were similar in the 2 groups. uDCD and DBD groups had similar rates for 10‐year death‐censored graft (82.1% vs 80.4%; P = .623) and recipient survival (86.2% vs 87.6%; P = .454). Donor age >50 years was associated with graft loss in the uDCD group (hazard ratio: 1.91; P = .058), whereas the occurrence of DGF showed no significant effect. uDCD KT under nECMO support resulted in similar graft function and long‐term outcomes compared with KT from standard criteria DBD donors. Increased donor age could negatively affect graft survival after uDCD donation.
Kidney transplant recipients from uncontrolled donation after circulatory death donors preserved with normothermic extracorporeal membrane oxygenation have long‐term outcomes comparable to recipients from standard criteria donation after brain death donors.
Antibody‐mediated rejection is responsible for 30%‐50% of renal graft failures. Differentiation of B cells into antibody‐producing plasmablasts depends on the collaboration of follicular helper T ...cells (Tfh). We analyzed circulating Tfh (cTfh) in kidney recipients and studied cTfh relationship with anti‐HLA antibody production and graft outcome. cTfh were longitudinally analyzed in a prospective cohort of patients (n = 206), pre‐ and posttransplantation. Clinical data, HLA sensitization, and cTfh function were recorded. Both pretransplant and 6‐month posttransplant cTfh were able to derive IgG‐producing plasmablasts. Pretransplant cTfh was decreased in patients, especially in those who received dialysis. However, these cells were increased in patients with previous allograft or transfusions and in HLA‐sensitized recipients. After transplantation cTfh expanded, significantly more in patients who developed de novo anti‐HLA antibodies than in patients who remained unsensitized. Augmented pretransplant cTfh positively correlated with higher intensity of pretransplant anti‐HLA class I and with de novo anti‐HLA class I and anti‐HLA class II antibodies. Consistently, pretransplantation cTfh were higher in patients who experienced acute rejection (HR = 1.14 1.04‐1.25). Thus, we show a role for Tfh in anti‐HLA sensitization and rejection. Multicenter studies with additional patient cohorts are needed to validate these results. Immunosuppressive drugs targeting Tfh could be useful to improve outcomes.
Circulating follicular helper T cells are associated with anti‐HLA antibody development and acute rejection in renal transplant patients, which points these cells out as a therapeutic target to improve transplant outcome.
The use of molecular techniques has put in the spotlight the existence of a large mass of malaria sub-microscopic infections among apparently healthy populations. These sub-microscopic infections are ...considered an important pool for maintained malaria transmission.
In order to assess the appearance of Plasmodium vivax gametocytes in circulation, gametocyte density and the parasite infectivity to Anopheles mosquitoes, a study was designed to compare three groups of volunteers either experimentally infected with P. vivax sporozoites (early infections; n = 16) or naturally infected patients (acute malaria, n = 16 and asymptomatic, n = 14). In order to determine gametocyte stage, a quantitative reverse transcriptase PCR (RT-qPCR) assay targeting two sexual stage-specific molecular markers was used. Parasite infectivity was assessed by membrane feeding assays (MFA).
In early infections P. vivax gametocytes could be detected starting at day 7 without giving rise to infected mosquitoes during 13 days of follow-up. Asymptomatic carriers, with presumably long-lasting infections, presented the highest proportion of mature gametocytes and were as infective as acute patients.
This study shows the potential role of P. vivax asymptomatic carriers in malaria transmission should be considered when new policies are envisioned to redirect malaria control strategies towards targeting asymptomatic infections as a tool for malaria elimination.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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