Global Leadership Initiative on Malnutrition-Diagnosed Malnutrition in Lung Transplant Candidates.

BACKGROUND AND AIMS: Malnutrition in lung transplantation (LT) candidates increases postoperative morbidity and mortality. Early diagnosis of malnutrition could attenuate adverse prognostic factors. This study aimed to assess the prevalence of nutritional risk and malnutrition using GLIM criteria in LT candidates and clinically characterize those with malnutrition. METHODS: A prospective longitudinal study was conducted from 2000 to 2020 of LT candidates who underwent complete nutritional assessment (nutritional screening, anthropometry, bioelectrical impedance, blood laboratory tests and malnutrition diagnosis using GLIM criteria). RESULTS: Obstructive diseases (45.6%), interstitial diseases (36.6%) and cystic fibrosis/non-cystic fibrosis bronchiectasis (15.4%) were the main conditions assessed for LT. Of the 1060 candidates evaluated, 10.6% were underweight according to BMI, 29% were at risk of malnutrition and 47% were diagnosed with malnutrition using GLIM criteria. Reduced muscle mass was the most frequent GLIM phenotypic criterion. Malnutrition was more prevalent in patients with cystic fibrosis/non-cystic fibrosis bronchiectasis (84.5%) and obstructive (45.4%) and interstitial (31.3%) diseases. GLIM criteria detected some degree of malnutrition in all diseases requiring LT and identified patients with higher CRP levels and worse respiratory function, anthropometric measurements and visceral protein and lipid profiles. CONCLUSIONS: LT candidates present a high prevalence of malnutrition using the GLIM algorithm. GLIM criteria detected malnutrition in all diseases requiring LT and defined patients with worse clinical-analytical profiles.

Airway Complications after Lung Transplantation-A Contemporary Series of 400 Bronchial Anastomoses from a Single Center.

(1) Objective: To determine whether recent advances in lung transplantation (LT) have reduced the incidence and changed the risk factors for airway complications (AC). (2) Methods: Retrospective analysis of patients receiving a lung transplant between January 2007 and January 2019. An AC was defined as a bronchoscopic abnormality in the airway, either requiring or not requiring an endoscopic or surgical intervention. Both univariable and multivariable analyses were performed to identify risk factors for AC. (3) Results: 285 lung transplants (170 single and 115 bilateral lung transplants) were analysed, comprising 400 anastomoses at risk. A total of 50 anastomoses resulted in AC (12%). There were 14 anastomotic and 11 non-anastomotic stenoses, 4 dehiscences, and 3 malacias. Independent predictors for AC were: gender male (OR: 4.18; p = 0.002), cardiac comorbidities (OR: 2.74; p = 0.009), prolonged postoperative mechanical ventilation (OR: 2.5; p = 0.02), PaO2/FiO2 < 300 mmHg at 24 h post-LT (OR: 2.48; p = 0.01), graft infection (OR: 2.16; p = 0.05), and post-LT isolation of Aspergillus spp. (OR: 2.63; p = 0.03). (4) Conclusions: In spite of advances in lung transplantation practice, the risk factors, incidence, and lethality of AC after LT remains unchanged. Graft dysfunction, an infected environment, and the need of prolonged mechanical ventilation remain an Achilles heel for AC.

Real-life use of cefiderocol for salvage therapy of severe infections due to carbapenem-resistant Gram-negative bacteria.

Treatment of infections caused by carbapenem-resistant Gram-negative bacteria (CR-GNB) is challenging and new active antibiotics are needed urgently. This study describes the efficacy and safety of cefiderocol in a retrospective series of 13 patients with severe CR-GNB infection and limited treatment options. Pseudomonas aeruginosa was the predominant CR-GNB (n=8), followed by Burkholderia cepacia (n=3), Sthenotrophomona maltophilia (n=1) and KPC-producing Klebsiella pneumoniae (n=1). The source of infection was nosocomial pneumonia in 92.3% of cases (12/13), of which 11 cases were ventilator-associated pneumonia. Five patients were lung transplant recipients (38.5%). The median duration of treatment was 10 days (range 6-21 days). No severe adverse effects required reducing the dose or interrupting the treatment. Clinical and microbiological cure were assessed 7 days after the end of treatment, and achieved in 84.6% (11/13) of patients. Crude mortality at day 28 was observed in 23.1% (3/13) of cases. Cefiderocol is a valid alternative for the treatment of susceptible CR-GNB infections in patients with limited therapeutic options.

The catastrophic floods in the Guadiana River basin since 1500 CE.

The task of retrieving information about past flood events is very important to reconstruct flood series data. In this work, a wide range of different sources including newspapers, technical reports, and books was consulted in order to recover information about catastrophic flood events in Badajoz (Spain). A set of 37 catastrophic floods of the Guadiana River that occurred in Badajoz in the winter months (DJFM - December, January, February, and March) have been recovered since 1500 CE. This strong seasonality constrain is due to the important influence of the large-scale circulation patterns in winter affecting the climate of the Iberian Peninsula. Moreover, it is found that there is a clear difference between a higher number of floods in the 19th and 20th centuries and a substantial lower value of floods in the 16th-18th centuries. Finally, we evaluated the long-term evolution and inter-annual variability of the precipitation and the main large-scale atmospheric circulation patterns that govern climate variability in Iberia (NAO and EA modes) for the period 1851-1985. This analysis suggests that most extreme floods observed in this period (26 events) correspond to consecutive months with higher than usual precipitation, driven in part by unusual values of both the NAO and the EA modes of variability.

Predictive Value of Immune Cell Functional Assay for Non-Cytomegalovirus Infection in Lung Transplant Recipients: A Multicenter Prospective Observational Study.

INTRODUCTION: Immune cell functional assay (ImmuKnow®) is a non-invasive method that measures the state of cellular immunity in immunosuppressed patients. We studied the prognostic value of the assay for predicting non-cytomegalovirus (CMV) infections in lung transplant recipients. METHODS: A multicenter prospective observational study of 92 patients followed up from 6 to 12 months after transplantation was performed. Immune cell functional assay was carried out at 6, 8, 10, and 12 months. RESULTS: Twenty-three patients (25%) developed 29 non-CMV infections between 6 and 12 months post-transplant. At 6 months, the immune response was moderate (ATP 225-525ng/mL) in 14 (15.2%) patients and low (ATP<225ng/mL) in 78 (84.8%); no patients had a strong response (ATP≥525ng/mL). Only 1 of 14 (7.1%) patients with a moderate response developed non-CMV infection in the following 6 months compared with 22 of 78 (28.2%) patients with low response, indicating sensitivity of 95.7%, specificity of 18.8%, positive predictive value (PPV) of 28.2%, and negative predictive value (NPV) of 92.9% (AUC 0.64; p=0.043). Similar acute rejection rates were recorded in patients with mean ATP≥225 vs. <225ng/mL during the study period (7.1% vs. 9.1%, p=0.81). CONCLUSION: Although ImmuKnow® does not seem useful to predict non-CMV infection, it could identify patients with a very low risk and help us define a target for an optimal immunosuppression.

Predictive Value of Immune Cell Functional Assay for Non-Cytomegalovirus Infection in Lung Transplant Recipients: A Multicenter Prospective Observational Study.

INTRODUCTION: Immune cell functional assay (ImmuKnow®) is a non-invasive method that measures the state of cellular immunity in immunosuppressed patients. We studied the prognostic value of the assay for predicting non-cytomegalovirus (CMV) infections in lung transplant recipients. METHODS: A multicenter prospective observational study of 92 patients followed up from 6 to 12 months after transplantation was performed. Immune cell functional assay was carried out at 6, 8, 10, and 12 months. RESULTS: Twenty-three patients (25%) developed 29 non-CMV infections between 6 and 12 months post-transplant. At 6 months, the immune response was moderate (ATP 225-525ng/mL) in 14 (15.2%) patients and low (ATP<225ng/mL) in 78 (84.8%); no patients had a strong response (ATP≥525ng/mL). Only 1 of 14 (7.1%) patients with a moderate response developed non-CMV infection in the following 6 months compared with 22 of 78 (28.2%) patients with low response, indicating sensitivity of 95.7%, specificity of 18.8%, positive predictive value (PPV) of 28.2%, and negative predictive value (NPV) of 92.9% (AUC 0.64; p=0.043). Similar acute rejection rates were recorded in patients with mean ATP≥225 vs. <225ng/mL during the study period (7.1% vs. 9.1%, p=0.81). CONCLUSION: Although ImmuKnow® does not seem useful to predict non-CMV infection, it could identify patients with a very low risk and help us define a target for an optimal immunosuppression.

Efficacy and safety of the combination of reduced duration prophylaxis followed by immuno-guided prophylaxis to prevent cytomegalovirus disease in lung transplant recipients (CYTOCOR STUDY): an open-label, randomised, non-inferiority clinical trial.

INTRODUCTION: Prolonged use of antivirals to prevent the development of cytomegalovirus (CMV) disease in lung transplant patients has been shown to have significant side effects, for which alternatives are being sought to reduce their use. The monitoring of cell immunity against CMV could be an alternative as it has shown to be useful in identifying transplant patients at low risk of infection, who could benefit from shorter prophylaxis. The aim of the CYTOCOR study is to demonstrate that the combination of a reduced prophylaxis strategy with subsequent CMV-specific immunological monitoring would allow CMV infection to be controlled in lung transplant patients as effectively as the usual strategy (prophylaxis followed by pre-emptive therapy), while reducing the side effects of antivirals due to the shorter duration of prophylaxis. METHODS AND ANALYSIS: Phase III randomised, open, multicentre, parallel, non-inferiority clinical trial to study the efficacy and safety of the combination of a prophylaxis strategy up to month +3 post-transplant followed by immuno-guided prophylaxis using the QuantiFERON-CMV technique up to month +12 post-transplant to prevent CMV disease in CMV-seropositive lung transplant recipients. This strategy will be compared with a combination of a usual prophylaxis strategy up to month +6 post-transplant followed by pre-emptive therapy up to month +12. To study the incidence of CMV disease, patients will be followed up to 18 months post-transplantation. A total of 150 patients are expected to be recruited for the study. ETHICS AND PUBLIC DISSEMINATION: The clinical trial has been approved by the Research Ethics Committees and authorised by the Spanish Agency of Medicines and Medical Devices (AEMPS).If the hypothesis of this clinical trial is verified, the dissemination of the results could change clinical practice by increasing knowledge about the safety and efficacy of discontinuing valganciclovir prophylaxis in lung transplant recipients. TRIAL REGISTRATION NUMBER: NCT03699254.

Early meteorological records from Latin-America and the Caribbean during the 18th and 19th centuries.

This paper provides early instrumental data recovered for 20 countries of Latin-America and the Caribbean (Argentina, Bahamas, Belize, Brazil, British Guiana, Chile, Colombia, Costa Rica, Cuba, Ecuador, France (Martinique and Guadalupe), Guatemala, Jamaica, Mexico, Nicaragua, Panama, Peru, Puerto Rico, El Salvador and Suriname) during the 18th and 19th centuries. The main meteorological variables retrieved were air temperature, atmospheric pressure, and precipitation, but other variables, such as humidity, wind direction, and state of the sky were retrieved when possible. In total, more than 300,000 early instrumental data were rescued (96% with daily resolution). Especial effort was made to document all the available metadata in order to allow further post-processing. The compilation is far from being exhaustive, but the dataset will contribute to a better understanding of climate variability in the region, and to enlarging the period of overlap between instrumental data and natural/documentary proxies.

Efficacy and safety of short-term treatment with isoniazid and rifampicin for latent tuberculosis infection in lung transplant candidates.

BACKGROUND: The current recommendation for the treatment of latent tuberculosis infection (LTBI) in solid organ transplant candidates is isoniazid for 9 months, but this treatment has the main problem of frequently reaching the posttransplant period. METHODS: This is the study of efficacy and safety of a 3-month regimen with isoniazid and rifampicin (3HR) in lung transplant candidates in the Reina Sofía Hospital in Córdoba. RESULTS: Three hundred and ninety-eight lung transplant patients were evaluated. Ninety-two (24.9%) had LTBI and just 22 received the 3HR treatment. One additional patient was treated because he had a history of previous incomplete treatment for active TB. None of the treated patients developed posttransplant tuberculosis compared to three of the 62 patients with LTBI who were not treated (4.8%). Three patients could not conclude the 3HR treatment (13%), but only two had adverse effects (8.7%). CONCLUSIONS: Treatment of LTBI in lung transplant candidates using a short course of 3HR appears to be effective and safe in preventing posttransplant TB in lung transplant recipients.

Extended recipients but not extended donors are associated with poor outcomes following lung transplantation.

OBJECTIVES: Extended donors (EDs) are safely used to increase the donor pool in lung transplantation (LT), but their influence in critically ill patients (extended recipients [ERs]) remains controversial. We compared LT outcomes matching optimal donors (ODs) or EDs with optimal recipients (ORs) or ERs. METHODS: Three hundred and sixty-five LTs were reviewed. ED criteria: age >55, PaO2/FiO2 < 350 mmHg, pulmonary infiltrates/purulent secretions and ischaemic times >6 h (single LT [SLT]) and >9 h (double LT [DLT]). ER criteria: pulmonary fibrosis or pulmonary hypertension, pretransplant intubation, age >60 years and bypass >2 h. Four groups were created: Group 1 (OD/OR), Group 2 (OD/ER), Group 3 (ED/OR) and Group 4 (ED/ER). Thirty-day mortality, primary graft dysfunction (PGD), onset of bronchiolitis obliterans syndrome (BOS), long-term survival and other transplant outcomes were compared between OD and ED, OR and ER and among the four groups of study. RESULTS: There were 151 SLTs and 214 DLTs. Donors: OD (n = 229) vs ED (n = 136); PGD 8 vs 10% (P = 0.43); 30-day mortality 19 vs 20% (P = 0.53) and survival (1, 5, 10 and 15 years) 67, 47, 34, 26 vs 69, 53, 46 and 29% (P = 0.33). Recipients: OR (n = 182) vs ER (n = 183); PGD 7 vs 10% (P = 0.10); 30-day mortality 15 vs 23% (P = 0.04) and survival (1, 5, 10 and 15 years): 73, 57, 46, 30 vs 61, 42, 29 and 23% (P = 0.002). Four donor/recipient (D/R) groups: Group 1 (n = 122), Group 2 (n = 106), Group 3 (n = 61), Group 4 (n = 76); PGD 10, 6, 3 and 16% (P = 0.05); 30-day mortality 13, 26, 19 and 20%, respectively (P = 0.13); survival (1, 5, 10 and 15 years) 74, 55, 44 and 35% (Group 1), 55, 39, 22 and 16% (Group 2), 70, 59, 48 and 26% (Group 3) and 68, 47, 37 and 22% (Group 4) (P = 0.004). No differences in the onset of BOS were observed among the four study groups. CONCLUSIONS: LT in critically ill recipients is associated with poor early and long-term outcomes, irrespective of the quality of the donor and length of ischaemic times.

CD45RA expression on HCMV-specific effector memory CD8+ T cells is associated with the duration and intensity of HCMV replication after transplantation.

In this cross-sectional study on 42 solid organ transplant recipients, the association of kinetics of human cytomegalovirus (HCMV) replication and EMRA HCMV-specific CD8+ T cells was investigated. Correlation was observed between the duration of HCMV replication after transplantation and CD45RA+CD27- (r=0.609; p=0.004), CD45RA+CD28- (r=0.579; p=0.008) or CD45RA+CCR7- (r=0.488; p=0.029) HCMV-specific CD8+ T cells percentages. In the multivariate regression analyses, CD45RA+CD27-, CD45RA+CD28- or CD45RA+CCR7- HCMV-specific CD8+ T cells percentages increased 5.58% (p=0.001), 5.35% (p=0.001) or 4.49% (p=0.012), respectively, with every 10-day increase in the duration of HCMV replication. Moreover, CD45RA+CD27- or CD45RA+CD28- frequencies increased 4.16% (p=0.024) or 3.58% (p=0.049), respectively, with every unity increase in log(10) genomes/mL. These observations support the major association between the frequency of EMRA HCMV-specific CD8+ T cells and the duration of post-transplant HCMV replication episodes in solid organ transplantation recipients.