Structurally silent peptide anchor modifications allosterically modulate T cell recognition in a receptor-dependent manner.

Presentation of peptides by class I MHC proteins underlies T cell immune responses to pathogens and cancer. The association between peptide binding affinity and immunogenicity has led to the engineering of modified peptides with improved MHC binding, with the hope that these peptides would be useful for eliciting cross-reactive immune responses directed toward their weak binding, unmodified counterparts. Increasing evidence, however, indicates that T cell receptors (TCRs) can perceive such anchor-modified peptides differently than wild-type (WT) peptides, although the scope of discrimination is unclear. We show here that even modifications at primary anchors that have no discernible structural impact can lead to substantially stronger or weaker T cell recognition depending on the TCR. Surprisingly, the effect of peptide anchor modification can be sensed by a TCR at regions distant from the site of modification, indicating a through-protein mechanism in which the anchor residue serves as an allosteric modulator for TCR binding. Our findings emphasize caution in the use and interpretation of results from anchor-modified peptides and have implications for how anchor modifications are accounted for in other circumstances, such as predicting the immunogenicity of tumor neoantigens. Our data also highlight an important need to better understand the highly tunable dynamic nature of class I MHC proteins and the impact this has on various forms of immune recognition.

Antithrombotic therapy-A simple algorithm for the interventional pathologist: A case series.

We can safely manage patients on antithrombotic therapy in the interventional pathology practice with this practical algorithm based on the new Antithrombotic Therapy Management Guidelines. This new algorithm helps ensure safe care for patients on antithrombotic therapy undergoing interventional pathology procedures. #interventionalpathology.

The Repellent Capacity against Sitophilus zeamais (Coleoptera: Curculionidae) and In Vitro Inhibition of the Acetylcholinesterase Enzyme of 11 Essential Oils from Six Plants of the Caribbean Region of Colombia.

The repellent capacity against Sitophilus zeamais and the in vitro inhibition on AChE of 11 essential oils, isolated from six plants of the northern region of Colombia, were assessed using a modified tunnel-type device and the Ellman colorimetric method, respectively. The results were as follows: (i) the degree of repellency (DR) of the EOs against S. zeamais was 20-68% (2 h) and 28-74% (4 h); (ii) the IC50 values on AChE were 5-36 µg/mL; likewise, the %inh. on AChE (1 µg/cm3 per EO) did not show any effect in 91% of the EO tested; (iii) six EOs (Bursera graveolens-bark, B. graveolens-leaves, B. simaruba-bark, Peperomia pellucida-leaves, Piper holtonii (1b*)-leaves, and P. reticulatum-leaves) exhibited a DR (53-74%) ≥ C+ (chlorpyrifos-61%), while all EOs were less active (8-60-fold) on AChE compared to chlorpyrifos (IC50 of 0.59 µg/mL). Based on the ANOVA/linear regression and multivariate analysis of data, some differences/similarities could be established, as well as identifying the most active EOs (five: B. simaruba-bark, Pep. Pellucida-leaves, P. holtonii (1b*)-leaves, B. graveolens-bark, and B. graveolens-leaves). Finally, these EOs were constituted by spathulenol (24%)/ß-selinene (18%)/caryophyllene oxide (10%)-B. simaruba; carotol (44%)/dillapiole (21%)-Pep. pellucida; dillapiole (81% confirmed by 1H-/13C-NMR)-P. holtonii; mint furanone derivative (14%)/mint furanone (14%)-B. graveolens-bark; limonene (17%)/carvone (10%)-B. graveolens-leaves.

Synchronous colorectal cancer and abdominal aortic aneurysm treated simultaneously. Is a one-stage surgery a feasible treatment?

The finding of synchronous abdominal aortic aneurysm and colorectal cancer is rare. There is no consensus on which is the best surgical approach, so its management remains uncertain. A 64-year-old man was diagnosed with synchronous abdominal aortic aneurysm and rectal cancer. One-stage treatment was performed: He underwent endovascular aortic repair followed by simultaneous laparoscopic tumor resection. In our experience, one-stage minimally invasive surgery could be a safe and feasible treatment for concomitant abdominal aortic aneurysm and colorectal cancer.

Structural dissimilarity from self drives neoepitope escape from immune tolerance.

T-cell recognition of peptides incorporating nonsynonymous mutations, or neoepitopes, is a cornerstone of tumor immunity and forms the basis of new immunotherapy approaches including personalized cancer vaccines. Yet as they are derived from self-peptides, the means through which immunogenic neoepitopes overcome immune self-tolerance are often unclear. Here we show that a point mutation in a non-major histocompatibility complex anchor position induces structural and dynamic changes in an immunologically active ovarian cancer neoepitope. The changes pre-organize the peptide into a conformation optimal for recognition by a neoepitope-specific T-cell receptor, allowing the receptor to bind the neoepitope with high affinity and deliver potent T-cell signals. Our results emphasize the importance of structural and physical changes relative to self in neoepitope immunogenicity. Considered broadly, these findings can help explain some of the difficulties in identifying immunogenic neoepitopes from sequence alone and provide guidance for developing novel, neoepitope-based personalized therapies.

WiFi FTM and UWB Characterization for Localization in Construction Sites.

A high-precision location is becoming a necessity in the future Industry 4.0 applications that will come up in the near future. However, the construction sector remains particularly obsolete in the adoption of Industry 4.0 applications. In this work, we study the accuracy and penetration capacity of two technologies that are expected to deal with future high-precision location services, such as ultra-wide band (UWB) and WiFi fine time measurement (FTM). For this, a measurement campaign has been performed in a construction environment, where UWB and WiFi-FTM setups have been deployed. The performance of UWB and WiFi-FTM have been compared with a prior set of indoors measurements. UWB seems to provide better ranging estimation in LOS conditions but it seems cancelled by reinforcement concrete for propagation and WiFi is able to take advantage of holes in the structure to provide location services. Moreover, the impact of fusion of location technologies has been assessed to measure the potential improvements in the construction scenario.

Early and late results of open surgical and endovascular treatment of infrarenal abdominal aortic aneurysms, selected according to surgical risk.

BACKGROUND: Open surgical repair (OSR) and endovascular aneurysm repair (EVAR) surgery are alternative treatments for infrarenal abdominal aortic aneurysm (IRAAA). OBJECTIVES: To compare OSR and EVAR for the treatment of IRAAA. METHODS: 119 patients with IRAAA were electively operated by the same surgeon between January 1, 2006 and December 31, 2015, following selection for OSR or EVAR according to surgical risk. Complications, reinterventions, failures, and early and late mortality were analyzed. RESULTS: 63 OSR and 56 EVAR patients were analyzed. They were similar in terms of age (70 years), gender (92% men), and average diameter of IRAAA (6.5 cm), but with different comorbidities, surgical risk, and anatomy. EVAR was better than OSR regarding time in the operating theatre (177.5 vs. 233.3 minutes), need for transfusion (25 vs. 73%), and length of stay in ICU (1.3 vs. 3.3 days) and hospital (8.1 vs. 11.1 days). OSR allowed more associated procedures to be conducted simultaneously (19.0 vs. 1.8%). There were no significant differences between the groups with respect to complications (25.4 vs. 25.1%), reinterventions (3.2 vs. 5.2%), or early mortality (1.6 vs. 0%). During follow-up, OSR was associated with fewer revisions (3.13 vs. 4.21), angio-CTs (0.22 vs. 3.23), complications (6.4 vs. 37.5%), reinterventions (3.2 vs. 23.2%), and failures (1.6 vs. 10.7%), and had better survival (78.2 vs. 63.2%). CONCLUSIONS: Correct selection of patients achieves excellent results because it avoids OSR in patients at high risk and avoids EVAR in patients with high anatomical complexity, achieving similar results in the perioperative period, but better results for OSR over the course of follow-up.

CONTEXTO: A cirurgia aberta (CA) e o reparo endovascular de aneurisma (REVA) são tratamentos alternativos para o aneurisma da aorta abdominal infrarrenal (AAAIR). OBJETIVOS: Comparar CA e REVA no tratamento do AAAIR. MÉTODOS: Foram incluídos 119 pacientes com AAAIR, operados eletivamente pelo mesmo cirurgião entre 1 de janeiro de 2006 e 31 de dezembro de 2015, após seleção para CA ou REVA de acordo com o risco cirúrgico. Complicações, reintervenções, falhas e mortalidade precoce e tardia foram analisadas. RESULTADOS: Foram analisados 63 pacientes de CA e 56 de REVA, com semelhanças de idade (70 anos), sexo (92% homens) e diâmetro médio do AAAIR (6,5 cm), mas com diferentes comorbidades, riscos cirúrgicos e anatomias. O REVA foi melhor que a CA em relação ao tempo na sala de cirurgia (177,5 vs. 233,3 minutos), necessidade de transfusão (25 vs. 73%) e tempo de permanência na unidade de terapia intensiva (1,3 vs. 3,3 dias) e no hospital (8,1 vs. 11,1 dias). A CA permitiu que mais procedimentos associados fossem realizados simultaneamente (19,0 vs. 1,8%). Não houve diferenças significativas entre os grupos em relação a complicações (25,4 vs. 25,1%), reintervenções (3,2 vs. 5,2%) e mortalidade precoce (1,6 vs. 0%). Durante o acompanhamento, a CA apresentou menos revisões (3,13 vs. 4,21), angiotomografias (0,22 vs. 3,23), complicações (6,4 vs. 37,5%), reintervenções (3,2 vs. 23,2%) e falhas (1,6 vs. 10,7%), além de ter melhor sobrevida (78,2 vs. 63,2%). CONCLUSÕES: A seleção correta dos pacientes proporciona excelentes resultados porque evita pacientes com alto risco para CA e com complexidade anatômica para REVA. Os resultados são semelhantes no período perioperatório, mas melhores para CA durante o acompanhamento.

An Engineered T Cell Receptor Variant Realizes the Limits of Functional Binding Modes.

T cell receptors (TCRs) orchestrate cellular immunity by recognizing peptides presented by a range of major histocompatibility complex (MHC) proteins. Naturally occurring TCRs bind the composite peptide/MHC surface, recognizing peptides that are structurally and chemically compatible with the TCR binding site. Here we describe a molecularly evolved TCR variant that binds the human class I MHC protein HLA-A2 independent of the bound peptide, achieved by a drastic perturbation of the TCR binding geometry that places the molecule far from the peptide binding groove. This unique geometry is unsupportive of normal T cell signaling. A substantial divergence between affinity measurements in solution and in two dimensions between proximal cell membranes leads us to attribute the lack of signaling to steric hindrance that limits binding in the confines of a cell-cell interface. Our results provide an example of how receptor binding geometry can impact T cell function and provide further support for the view that germline-encoded residues in TCR binding loops evolved to drive productive TCR recognition and signaling.

T cell receptor cross-reactivity expanded by dramatic peptide-MHC adaptability.

T cell receptor cross-reactivity allows a fixed T cell repertoire to respond to a much larger universe of potential antigens. Recent work has emphasized the importance of peptide structural and chemical homology, as opposed to sequence similarity, in T cell receptor cross-reactivity. Surprisingly, though, T cell receptors can also cross-react between ligands with little physiochemical commonalities. Studying the clinically relevant receptor DMF5, we demonstrate that cross-recognition of such divergent antigens can occur through mechanisms that involve heretofore unanticipated rearrangements in the peptide and presenting MHC protein, including binding-induced peptide register shifts and extensions from MHC peptide binding grooves. Moreover, cross-reactivity can proceed even when such dramatic rearrangements do not translate into structural or chemical molecular mimicry. Beyond demonstrating new principles of T cell receptor cross-reactivity, our results have implications for efforts to predict and control T cell specificity and cross-reactivity and highlight challenges associated with predicting T cell reactivities.

Improving T Cell Receptor On-Target Specificity via Structure-Guided Design.

T cell receptors (TCRs) have emerged as a new class of immunological therapeutics. However, though antigen specificity is a hallmark of adaptive immunity, TCRs themselves do not possess the high specificity of monoclonal antibodies. Although a necessary function of T cell biology, the resulting cross-reactivity presents a significant challenge for TCR-based therapeutic development, as it creates the potential for off-target recognition and immune toxicity. Efforts to enhance TCR specificity by mimicking the antibody maturation process and enhancing affinity can inadvertently exacerbate TCR cross-reactivity. Here we demonstrate this concern by showing that even peptide-targeted mutations in the TCR can introduce new reactivities against peptides that bear similarity to the original target. To counteract this, we explored a novel structure-guided approach for enhancing TCR specificity independent of affinity. Tested with the MART-1-specific TCR DMF5, our approach had a small but discernible impact on cross-reactivity toward MART-1 homologs yet was able to eliminate DMF5 cross-recognition of more divergent, unrelated epitopes. Our study provides a proof of principle for the use of advanced structure-guided design techniques for improving TCR specificity, and it suggests new ways forward for enhancing TCRs for therapeutic use.

A Digital Signal Processor Based Acoustic Sensor for Outdoor Noise Monitoring in Smart Cities.

Presently, large cities have significant problems with noise pollution due to human activity. Transportation, economic activities, and leisure activities have an important impact on noise pollution. Acoustic noise monitoring must be done with equipment of high quality. Thus, long-term noise monitoring is a high-cost activity for administrations. For this reason, new alternative technological solutions are being used to reduce the costs of measurement instruments. This article presents a design for a versatile electronic device to measure outdoor noise. This device has been designed according to the technical standards for this type of instrument, which impose strict requirements on both the design and the quality of the device's measurements. This instrument has been designed under the original equipment manufacturer (OEM) concept, so the microphone-electronics set can be used as a sensor that can be connected to any microprocessor-based device, and therefore can be easily attached to a monitoring network. To validate the instrument's design, the device has been tested following the regulations of the calibration laboratories for sound level meters (SLM). These tests allowed us to evaluate the behavior of the electronics and the microphone, obtaining different results for these two elements. The results show that the electronics and algorithms implemented fully fit within the requirements of type 1 noise measurement instruments. However, the use of an electret microphone reduces the technical features of the designed instrument, which can only fully fit the requirements of type 2 noise measurement instruments. This situation shows that the microphone is a key element in this kind of instrument and an important element in the overall price. To test the instrument's quality and show how it can be used for monitoring noise in smart wireless acoustic sensor networks, the designed equipment was connected to a commercial microprocessor board and inserted into the infrastructure of an existing outdoor monitoring network. This allowed us to deploy a low-cost sub-network in the city of Málaga (Spain) to analyze the noise of conflict areas due to high levels of leisure noise. The results obtained with this equipment are also shown. It has been verified that this equipment meets the similar requirements to those obtained for type 2 instruments for measuring outdoor noise. The designed equipment is a two-channel instrument, that simultaneously measures, in real time, 86 sound noise parameters for each channel, such as the equivalent continuous sound level (Leq) (with Z, C, and A frequency weighting), the peak level (with Z, C, and A frequency weighting), the maximum and minimum levels (with Z, C, and A frequency weighting), and the impulse, fast, and slow time weighting; seven percentiles (1%, 5%, 10%, 50%, 90%, 95%, and 99%); as well as continuous equivalent sound pressure levels in the one-third octave and octave frequency bands.

Dual endovascular repair (coils and stent) of a true aneurysm of the gastroduodenal artery.

We report a case of an asymptomatic gastroduodenal artery aneurysm diagnosed in a 39 year-old woman. An abdominal ultrasound study showed an aneurysmal dilatation of the gastroduodenal artery with 2 x 2 cm diameter. To confirm this finding, she then underwent a computed tomography scan of the abdomen and pelvis that showed a saccular aneurysm of the gastroduodenal artery. A dual endovascular approach was used to exclude the aneurysm by stent-assisted coil embolization. Complete exclusion of the aneurysm sac was confirmed on final angiography. She was discharged from the hospital on postoperative day 1.

Relatamos um caso de aneurisma de artéria gastroduodenal assintomático diagnosticado em uma mulher de 39 anos. Uma ultrassonografia abdominal mostrou uma dilatação aneurismática associada à artéria gastroduodenal com 2 x 2 cm de diâmetro. Para confirmar esse achado, foi realizada uma tomografia computadorizada do abdome e da pelve, que revelou um aneurisma sacular da artéria gastroduodenal. Uma abordagem endovascular dupla foi utilizada para exclusão do aneurisma mediante embolização com molas assistida por stent. A exclusão completa do saco aneurismático foi confirmada na angiografia final. A paciente recebeu alta hospitalar no primeiro dia de pós-operatório.

Monitoring an Analysis of Perturbations in Fusion Deposition Modelling (FDM) Processes for the Use of Biomaterials.

During an FDM production process, there are different external disturbances to the characteristics of the machine that can affect to the production process. These disturbances will cause the final result differs from the desired one. Moreover, these disturbances, such as temperature or chamber humidity, are extremely important in case of using biocompatible materials. The use of these kind of materials with not controlled environment, can cause them to modify or loss of their properties; what will make the product unusable. Apart from these external disturbances, the conditions of the machine to which the material is subjected must also be considered, such as temperature, vibrations or extrusion speed. The monitoring of all these data will allow to know the conditions to which the product was exposed during the process. In this way, it will be able to verify the validity of the final product. For these reasons, the purpose of this work is to monitor the conditions of production of structures with biocompatible materials by fused deposition modelling (FDM) technique. This monitoring will allow us to obtain a report that guarantee the technical and geometrical characteristics of the model and the biomaterial properties. The parameters chosen to be monitored are: Diameter of filament use, temperature in extrusion nozzle, ambient temperature in closed chamber, ambient humidity in closed chamber. The obtained results, after collected and analysing the data, present variations of up to 3% in the temperature of the nozzle of the extruder with respect to set temperature. In the case of the filament diameter the difference with respect to the value provided from the filament supplier is of 13,7%. In addition, the results show how the ambient humidity in closed chamber has changed by 2 percentage points and the ambient temperature in closed chamber has been increased 6,52 °C with respect to the set values.

Integrated Framework for Assessing Impacts of CO2 Leakage on Groundwater Quality and Monitoring-Network Efficiency: Case Study at a CO2 Enhanced Oil Recovery Site.

This study presents a combined use of site characterization, laboratory experiments, single-well push-pull tests (PPTs), and reactive transport modeling to assess potential impacts of CO2 leakage on groundwater quality and leakage-detection ability of a groundwater monitoring network (GMN) in a potable aquifer at a CO2 enhanced oil recovery (CO2 EOR) site. Site characterization indicates that failures of plugged and abandoned wells are possible CO2 leakage pathways. Groundwater chemistry in the shallow aquifer is dominated mainly by silicate mineral weathering, and no CO2 leakage signals have been detected in the shallow aquifer. Results of the laboratory experiments and the field test show no obvious damage to groundwater chemistry should CO2 leakage occur and further were confirmed with a regional-scale reactive transport model (RSRTM) that was built upon the batch experiments and validated with the single-well PPT. Results of the RSRTM indicate that dissolved CO2 as an indicator for CO2 leakage detection works better than dissolved inorganic carbon, pH, and alkalinity at the CO2 EOR site. The detection ability of a GMN was assessed with monitoring efficiency, depending on various factors, including the natural hydraulic gradient, the leakage rate, the number of monitoring wells, the aquifer heterogeneity, and the time for a CO2 plume traveling to the monitoring well.

Ebola virus does not block apoptotic signaling pathways.

Since viruses rely on functional cellular machinery for efficient propagation, apoptosis is an important mechanism to fight viral infections. In this study, we sought to determine the mechanism of cell death caused by Ebola virus (EBOV) infection by assaying for multiple stages of apoptosis and hallmarks of necrosis. Our data indicate that EBOV does not induce apoptosis in infected cells but rather leads to a nonapoptotic form of cell death. Ultrastructural analysis confirmed necrotic cell death of EBOV-infected cells. To investigate if EBOV blocks the induction of apoptosis, infected cells were treated with different apoptosis-inducing agents. Surprisingly, EBOV-infected cells remained sensitive to apoptosis induced by external stimuli. Neither receptor- nor mitochondrion-mediated apoptosis signaling was inhibited in EBOV infection. Although double-stranded RNA (dsRNA)-induced activation of protein kinase R (PKR) was blocked in EBOV-infected cells, induction of apoptosis mediated by dsRNA was not suppressed. When EBOV-infected cells were treated with dsRNA-dependent caspase recruiter (dsCARE), an antiviral protein that selectively induces apoptosis in cells containing dsRNA, virus titers were strongly reduced. These data show that the inability of EBOV to block apoptotic pathways may open up new strategies toward the development of antiviral therapeutics.

Field demonstration of CO2 leakage detection in potable aquifers with a pulselike CO2-release test.

This study presents two field pulselike CO2-release tests to demonstrate CO2 leakage detection in a shallow aquifer by monitoring groundwater pH, alkalinity, and dissolved inorganic carbon (DIC) using the periodic groundwater sampling method and a fiber-optic CO2 sensor for real-time in situ monitoring of dissolved CO2 in groundwater. Measurements of groundwater pH, alkalinity, DIC, and dissolved CO2 clearly deviated from their background values, showing responses to CO2 leakage. Dissolved CO2 observed in the tests was highly sensitive in comparison to groundwater pH, DIC, and alkalinity. Comparison of the pulselike CO2-release tests to other field tests suggests that pulselike CO2-release tests can provide reliable assessment of geochemical parameters indicative of CO2 leakage. Measurements by the fiber-optic CO2 sensor, showing obvious leakage signals, demonstrated the potential of real-time in situ monitoring of dissolved CO2 for leakage detection at a geologic carbon sequestration (GCS) site. Results of a two-dimensional reactive transport model reproduced the geochemical measurements and confirmed that the decrease in groundwater pH and the increases in DIC and dissolved CO2 observed in the pulselike CO2-release tests were caused by dissolution of CO2 whereas alkalinity was likely affected by carbonate dissolution.

Dysuria and acute urinary retencion as initial presentation of primary vaginal lymphoma. Case report and bibliographic review.

OBJECTIVE: We report a case of primary vaginal lymphoma. The clinical presentation was an episode of dysuria and acute urinary retention. We performed a bibliographic review. METHODS: Thirty-six year-old patient who consulted in the urology clinic for hesitancy that triggered an episode of acute urinary retention. Physical examination revealed thickening of the vaginal wall. Biopsy was performed and diagnosis of diffuse large B-cell primary vaginal non-Hodgkin's lymphoma was obtained. RESULTS: Primary lymphomas of the female genital tract are rare. The third most frequent location is vagina. The most common manifestation is vaginal bleeding. Urinary symptoms are rarely the first sign. Diagnosis requires a biopsy. The first choice for treatment is Rituximab- CHOP immuno-chemotherapy. CONCLUSIONS: Vaginal lymphoma is a rare disease. Unfrequently, the first clinical manifestations are urinary tract symptoms, and even less acute urinary retention.

Challenges in Septic Shock: From New Hemodynamics to Blood Purification Therapies.

Sepsis and septic shock are associated with high mortality, with diagnosis and treatment remaining a challenge for clinicians. Their management classically encompasses hemodynamic resuscitation, antibiotic treatment, life support, and focus control; however, there are aspects that have changed. This narrative review highlights current and avant-garde methods of handling patients experiencing septic shock based on the experience of its authors and the best available evidence in a context of uncertainty. Following the first recommendation of the Surviving Sepsis Campaign guidelines, it is recommended that specific sepsis care performance improvement programs are implemented in hospitals, i.e., "Sepsis Code" programs, designed ad hoc, to achieve this goal. Regarding hemodynamics, the importance of perfusion and hemodynamic coherence stand out, which allow for the recognition of different phenotypes, determination of the ideal time for commencing vasopressor treatment, and the appropriate fluid therapy dosage. At present, this is not only important for the initial timing, but also for de-resuscitation, which involves the early weaning of support therapies, directed elimination of fluids, and fluid tolerance concept. Finally, regarding blood purification therapies, those aimed at eliminating endotoxins and cytokines are attractive in the early management of patients in septic shock.

Strategies to address diabetic kidney disease burden in Mexico: a narrative review by the Mexican College of Nephrologists.

Chronic kidney disease (CKD) is a growing global public health challenge worldwide. In Mexico, CKD prevalence is alarmingly high and remains a leading cause of morbidity and mortality. Diabetic kidney disease (DKD), a severe complication of diabetes, is a leading determinant of CKD. The escalating diabetes prevalence and the complex regional landscape in Mexico underscore the pressing need for tailored strategies to reduce the burden of CKD. This narrative review, endorsed by the Mexican College of Nephrologists, aims to provide a brief overview and specific strategies for healthcare providers regarding preventing, screening, and treating CKD in patients living with diabetes in all care settings. The key topics covered in this review include the main cardiometabolic contributors of DKD (overweight/obesity, hyperglycemia, arterial hypertension, and dyslipidemia), the identification of kidney-related damage markers, and the benefit of novel pharmacological approaches based on Sodium-Glucose Co-Transporter-2 Inhibitors (SGLT2i) and Glucagon-Like Peptide-1 Receptor Agonists (GLP-1 RA). We also address the potential use of novel therapies based on Mineralocorticoid Receptor Antagonists (MRAs) and their future implications. Emphasizing the importance of multidisciplinary treatment, this narrative review aims to promote strategies that may be useful to alleviate the burden of DKD and its associated complications. It underscores the critical role of healthcare providers and advocates for collaborative efforts to enhance the quality of life for millions of patients affected by DKD.

Individualised, perioperative open-lung ventilation strategy during one-lung ventilation (iPROVE-OLV): a multicentre, randomised, controlled clinical trial.

BACKGROUND: It is uncertain whether individualisation of the perioperative open-lung approach (OLA) to ventilation reduces postoperative pulmonary complications in patients undergoing lung resection. We compared a perioperative individualised OLA (iOLA) ventilation strategy with standard lung-protective ventilation in patients undergoing thoracic surgery with one-lung ventilation. METHODS: This multicentre, randomised controlled trial enrolled patients scheduled for open or video-assisted thoracic surgery using one-lung ventilation in 25 participating hospitals in Spain, Italy, Turkey, Egypt, and Ecuador. Eligible adult patients (age ≥18 years) were randomly assigned to receive iOLA or standard lung-protective ventilation. Eligible patients (stratified by centre) were randomly assigned online by local principal investigators, with an allocation ratio of 1:1. Treatment with iOLA included an alveolar recruitment manoeuvre to 40 cm H2O of end-inspiratory pressure followed by individualised positive end-expiratory pressure (PEEP) titrated to best respiratory system compliance, and individualised postoperative respiratory support with high-flow oxygen therapy. Participants allocated to standard lung-protective ventilation received combined intraoperative 4 cm H2O of PEEP and postoperative conventional oxygen therapy. The primary outcome was a composite of severe postoperative pulmonary complications within the first 7 postoperative days, including atelectasis requiring bronchoscopy, severe respiratory failure, contralateral pneumothorax, early extubation failure (rescue with continuous positive airway pressure, non-invasive ventilation, invasive mechanical ventilation, or reintubation), acute respiratory distress syndrome, pulmonary infection, bronchopleural fistula, and pleural empyema. Due to trial setting, data obtained in the operating and postoperative rooms for routine monitoring were not blinded. At 24 h, data were acquired by an investigator blinded to group allocation. All analyses were performed on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, NCT03182062, and is complete. FINDINGS: Between Sept 11, 2018, and June 14, 2022, we enrolled 1380 patients, of whom 1308 eligible patients (670 [434 male, 233 female, and three with missing data] assigned to iOLA and 638 [395 male, 237 female, and six with missing data] to standard lung-protective ventilation) were included in the final analysis. The proportion of patients with the composite outcome of severe postoperative pulmonary complications within the first 7 postoperative days was lower in the iOLA group compared with the standard lung-protective ventilation group (40 [6%] vs 97 [15%], relative risk 0·39 [95% CI 0·28 to 0·56]), with an absolute risk difference of -9·23 (95% CI -12·55 to -5·92). Recruitment manoeuvre-related adverse events were reported in five patients. INTERPRETATION: Among patients subjected to lung resection under one-lung ventilation, iOLA was associated with a reduced risk of severe postoperative pulmonary complications when compared with conventional lung-protective ventilation. FUNDING: Instituto de Salud Carlos III and the European Regional Development Funds.