New variants expand the neurological phenotype of COQ7 deficiency.

The protein encoded by COQ7 is required for CoQ10 synthesis in humans, hydroxylating 3-demethoxyubiquinol (DMQ10) in the second to last steps of the pathway. COQ7 mutations lead to a primary CoQ10 deficiency syndrome associated with a pleiotropic neurological disorder. This study shows the clinical, physiological, and molecular characterization of four new cases of CoQ10 primary deficiency caused by five mutations in COQ7, three of which have not yet been described, inducing mitochondrial dysfunction in all patients. However, the specific combination of the identified variants in each patient generated precise pathophysiological and molecular alterations in fibroblasts, which would explain the differential in vitro response to supplementation therapy. Our results suggest that COQ7 dysfunction could be caused by specific structural changes that affect the interaction with COQ9 required for the DMQ10 presentation to COQ7, the substrate access to the active site, and the maintenance of the active site structure. Remarkably, patients' fibroblasts share transcriptional remodeling, supporting a modification of energy metabolism towards glycolysis, which could be an adaptive mechanism against CoQ10 deficiency. However, transcriptional analysis of mitochondria-associated pathways showed distinct and dramatic differences between patient fibroblasts, which correlated with the extent of pathophysiological and neurological alterations observed in the probands. Overall, this study suggests that the combination of precise genetic diagnostics and the availability of new structural models of human proteins could help explain the origin of phenotypic pleiotropy observed in some genetic diseases and the different responses to available therapies.

Volatiles of symbiotic bacterial origin explain ectoparasitism and fledging success of hoopoes.

BACKGROUND: Some parasites use olfactory cues to detect their hosts and, since bacterial symbionts are partially responsible for animal odours, they could influence host parasitism. By autoclaving nest materials of hoopoe (Upupa epops) nests before reproduction started, we explored the hypothetical links between host-associated bacteria, volatiles and parasitism. During the nestling stage, we (i) estimated the level of ectoparasitism by chewing lice (Suborder Mallophaga) in adult hoopoe females and by Carnus haemapterus flies in nestlings, and (ii) characterized microbial communities and volatile profiles of nest environments (nest material and nest cavity, respectively) and uropygial secretions. RESULTS: Experimental nests had less diverse bacterial communities and more diverse volatile profiles than control nests, while occupants experienced lower intensity of parasitism in experimental than in control nests. The experiment also affected beta diversity of the microbial communities of nest material and of the volatiles of the nestling uropygial secretions. Moreover, microbial communities of uropygial secretions and of nest materials covaried with their volatile profiles, while the volatile profile of the bird secretions explained nest volatile profile. Finally, a subset of the volatiles and bacteria detected in the nest material and uropygial secretions were associated with the ectoparasitism intensity of both adult females and nestlings, and with fledging success. CONCLUSIONS: These results show that a component of animal odours is linked with the microbial communities of the host and its reproductive environment, and emphasize that the associations between bacteria, ectoparasitism and reproductive success are partially mediated by volatiles of bacterial origin. Future work should focus on mechanisms underlying the detected patterns.

Beyond the patella: Treatment of cam femoroacetabular impingement syndrome improves anterior knee pain.

OBJECTIVES: This study aimed to investigate if there is a relationship between cam femoroacetabular impingement syndrome (cam-FAIS) and chronic anterior knee pain (AKP). METHODS: This is a pilot retrospective review of 12 AKP patients with no structural anomalies in the patellofemoral joint and no skeletal malalignment in the lower limbs. All the patients were resistant to proper conservative treatment for AKP (AKP-R). Subsequently, these patients developed pain in the ipsilateral hip several months later, and upon evaluation, were diagnosed with cam-FAIS. Arthroscopic femoral osteoplasty and labral repair were performed and clinical follow-up of hip and knee pain and function (Kujala Score and Non-arthritic Hip Score -NAHS-) was carried out. RESULTS: All the patients showed improvement in the knee and hip pain scores with a statistically significant clinical difference in all of them at 69 months follow up (range: 18 to 115) except one patient without improvement in the groin VAS score post-operatively. Visual analogical scale (VAS) of knee pain improved from 6.3 (range: 5 to 8) to a postoperative 0.5 (range: 0 to 3.5), (p â€‹< â€‹0.001). The VAS of groin pain improved from 4.4 (range: 2 to 8) to a postoperative 0.9 (range: 0 to 3), (p â€‹< â€‹0.001). NAHS improved from a preoperative 67.9 (range: 28.7 to 100) to a postoperative 88 (range: 70 to 100), (p â€‹< â€‹0.015) and knee Kujala's score improved from a preoperative 48.7 (range: 22 to 71) to a postoperative 96 (range: 91 to 100), (p â€‹< â€‹0.001). CONCLUSION: This study's principal finding suggests an association between cam-FAIS and AKP-R in young patients who exhibit normal knee imaging and lower limbs skeletal alignment. Addressing cam-FAIS in these cases leads to resolution of both groin and knee pain, resulting in improved functional outcomes for both joints. STUDY DESIGN: Retrospective cohort series with a single contemporaneous long-term follow-up. LEVEL OF EVIDENCE: IV.

Extra Nestlings That Are Condemned to Die Increase Reproductive Success in Hoopoes.

AbstractThe adaptive value of routinely laying more eggs than can be successfully fledged has intrigued evolutionary biologists for decades. Extra eggs could, for instance, be adaptive as insurance against hatching failures. Moreover, because recent literature demonstrates that sibling cannibalism is frequent in the Eurasian hoopoe (Upupa epops), producing extra offspring that may be cannibalized by older siblings might also be adaptive in birds. Here, directed to explore this possibility in hoopoes, we performed a food supplementation experiment during the laying period and a clutch size manipulation during the hatching stage. We found that females with the food supplement laid on average one more egg than control females and that the addition of a close-to-hatch egg at the end of the hatching period increased the intensity of sibling cannibalism and enhanced fledging success in hoopoe nests. Because none of the extra nestlings from the experimental extra eggs survived until fledging, these results strongly suggest that hoopoes obtain fitness advantages by using temporarily abundant resources to produce additional nestlings that will be cannibalized. These results therefore suppose the first experimental demonstration of the nutritive adaptive function of laying extra eggs in vertebrates with parental care.

Predicting the Length of Mechanical Ventilation in Acute Respiratory Disease Syndrome Using Machine Learning: The PIONEER Study.

Background: The ability to predict a long duration of mechanical ventilation (MV) by clinicians is very limited. We assessed the value of machine learning (ML) for early prediction of the duration of MV > 14 days in patients with moderate-to-severe acute respiratory distress syndrome (ARDS). Methods: This is a development, testing, and external validation study using data from 1173 patients on MV ≥ 3 days with moderate-to-severe ARDS. We first developed and tested prediction models in 920 ARDS patients using relevant features captured at the time of moderate/severe ARDS diagnosis, at 24 h and 72 h after diagnosis with logistic regression, and Multilayer Perceptron, Support Vector Machine, and Random Forest ML techniques. For external validation, we used an independent cohort of 253 patients on MV ≥ 3 days with moderate/severe ARDS. Results: A total of 441 patients (48%) from the derivation cohort (n = 920) and 100 patients (40%) from the validation cohort (n = 253) were mechanically ventilated for >14 days [median 14 days (IQR 8-25) vs. 13 days (IQR 7-21), respectively]. The best early prediction model was obtained with data collected at 72 h after moderate/severe ARDS diagnosis. Multilayer Perceptron risk modeling identified major prognostic factors for the duration of MV > 14 days, including PaO2/FiO2, PaCO2, pH, and positive end-expiratory pressure. Predictions of the duration of MV > 14 days showed modest discrimination [AUC 0.71 (95%CI 0.65-0.76)]. Conclusions: Prolonged MV duration in moderate/severe ARDS patients remains difficult to predict early even with ML techniques such as Multilayer Perceptron and using data at 72 h of diagnosis. More research is needed to identify markers for predicting the length of MV. This study was registered on 14 August 2023 at ClinicalTrials.gov (NCT NCT05993377).

The distal tibiofibular syndesmosis is a reliable landmark for 3° varus tibial resection in total knee arthroplasty: a radiological evaluation on 1296 cases.

PURPOSE: The purpose of this study was to evaluate the reproducibility and the accuracy of distal tibiofibular syndesmosis (DTFS) as landmark to perform controlled varus tibial resections during total knee arthroplasty (TKA). The hypothesis was that DTFS can be used to perform an accurate 3° varus tibial cut. METHODS: A retrospective analysis on a consecutive series of standard weightbearing full-length anteroposterior views of the lower limbs radiographic images was conducted. For each radiograph, the hip-knee-ankle (HKA) angle, the angle between the tibial mechanical axis and the line connecting the centre of the tibial spines and the DTFS (tibiofibular angle, TFA) and the medial proximal tibial angle (MPTA) were calculated. Each measurement was carried out twice by three independent observers, and intra- and inter-observer measurement reliability were assessed using the intraclass correlation coefficient (ICC) analysis. RESULTS: A total of 1296 lower limbs were analysed from a series of 648 weightbearing full-length anteroposterior radiographs. The ICC were > 90% for all measurements. The mean TFA value was 2.94 ± 0.68 (range 2.38-3.51). No differences were detected comparing the mean TFA value on the right and left limb (p = 0.795) as well as comparing the values in male and female patients (p = 0.691). Linear regression analysis did not find statistically significant correlation between TFA and MPTA, or TFA and HKA angles, respectively. CONCLUSION: The distal tibiofibular syndesmosis is a reliable and easy reproducible radiographic landmark that can be used when planning a 3° varus tibial cut. Future studies are needed to confirm the validity of this method also in clinical settings. LEVEL OF EVIDENCE: IV, retrospective case series.

Psychometric evaluation of the Spanish version of the Pediatric Quality of Life Eosinophilic Esophagitis Questionnaire (Peds QL-EoE Module ™).

BACKGROUND: The Paediatric Eosinophilic Oesophagitis Module (PedsQL-EoE) was developed in English as a valid and reliable questionnaire to assess health-related quality of life (HRQoL) in children with EoE. The aim of this study was to evaluate the validity and reliability of the PedsQL-EoE that was previously adapted to Spanish by our group. METHODS: This cross-sectional multicentre study was conducted in 36 paediatric gastroenterology units. Groups with and without dietary restrictions were studied separately. The PedsQL-EoE consists of 33 items divided into seven factors. Age-specific versions of the PedsQL-EoE were sent by e-mail to children and parents. Statistical analysis was used to study the questionnaire structure by means of exploratory factor analysis and interitem correlations. Confirmatory factor analysis (CFA) was applied to verify the proposed model as well as its psychometric properties through SMSR (standardized root mean square), outer loadings and R-square. To study construct validity and reliability, Cronbach´s alpha coefficient, convergent validity (AVE), discriminant validity (HTMT) and intraclass correlation coefficients (ICC) were used. RESULTS: A total of 341 children and 394 parents participated with 307 matched answers. The median age was 12 years, and 75% were male. The questionnaire structure explained 68% and 66% of the total variance for parents and children, respectively. Five items showed negative correlations and were removed from the questionnaire. CFA applied to the new model supported the following construct: SMRS was less than 0.08, outer loadings measured above 0.5, and R2 explained more than 89% of the total variance. Once the modifications were performed, good internal consistency was demonstrated, with Cronbach's alpha values > 0.7, AVE values > 0.5 and HTMT < 0.9 with good child/parent agreement (ICC = 0.80). The most robust model of the PedsQL-EoE module was formed by seven factors: Symptoms I (6 items), Symptoms II (4 items), Treatment (4 items), Worries (3 items), Communication (5 items), Food and Eating (3 items) and Food Feelings (3 items). CONCLUSIONS: The final PedsQL-EoE Module version, after the removal of five items, is a valid and reliable tool to be used in children with EoE. The Spanish validated version appears to be a useful instrument for measuring the impact of EoE on Spanish children´s quality of life.

Food supply and provisioning behavior of parents: Are small hoopoe nestlings condemned to die?

Parents might use signals of need or of quality to decide food provisioning among their offspring, while the use of one or another signal might depend on food availability. Begging success of nestlings of different quality (i.e., body size) would also depend on food availability, and we here explore the effect of experimental food supply in begging success of nestlings and in provisioning of female hoopoes (Upupa epops), a species with extreme hatching asynchrony and nestlings size hierarchy. We video-recorded food allocation of females, begging success of nestlings of different size, and the social context (i.e., the size category of the other nestlings that were begging for food) during periods when experimental food supply was or was not available in the same nests. We found that when experimental food supplementation was present, begging success of the intermediate, but not that of large or small-sized nestlings, increased. The experiment, however, did not affect the feeding preferences of females toward nestlings of different size. Moreover, when small nestlings were the only ones that were begging for food, their begging success decreased in the experimental period, and females used supplemented prey to feed themselves. Those results, on one hand, confirm the importance of food availability for the begging success of nestlings of particular sizes and, on the other, indicate that females prefer to use extra food for their own rather than for the smallest nestlings. We discuss possible mechanisms explaining the detected experimental effects and the adaptive and nonadaptive explanations of mothers ignoring the small nestlings.

Hiperfiltración glomerular en el paciente traumático grave / Glomerular hyperfiltration in patients with severe trauma

Antecedentes y objetivo El aclaramiento renal aumentado o hiperfiltración glomerular (HFG) puede afectar significativamente a los resultados clínicos de los fármacos eliminados por vía renal al promover la exposición subterapéutica al fármaco. La agresión sufrida en los pacientes que presentan trauma grave supone un predisponente a manifestar HFG y la identificación de estos pacientes sigue siendo un desafío clínico. El objetivo principal de este estudio fue describir la prevalencia de HFG en una cohorte de pacientes críticos traumatizados en la primera semana de ingreso. Materiales y métodos Estudio prospectivo observacional de una cohorte de pacientes adultos ingresados en la UCI de Anestesiología del Complejo Hospitalario Universitario de Albacete (España) tras sufrir un trauma grave o politraumatismo. Se calculó el aclaramiento de creatinina (ClCr) en muestra de recolección de orina 4h a las 24, 72 y 168h de ingreso aplicando la fórmula ClCr: [Diuresis en ml (orina/4h)×Creatinina en orina (mg/dl)]÷[240 (minutos)×Creatinina en plasma (mg/dl)]. Un CrCl por encima de 130ml/min fue considerado HFG. Los análisis se realizaron con el software estadístico R versión 4.0.4. Resultados Se incluyeron 85 pacientes. La edad mediana de los pacientes fue de 51 años (RIQ 26); 68 pacientes fueron varones (78,82%). El 75,29% de los pacientes fueron politraumatizados; 61 pacientes (71,76%) presentaron HFG en algún momento de la determinación del ClCr. A las 24h de ingreso el 56,34% de los pacientes presentaron HFG con ClCr medio de 195,8ml/min, el 61,11% de los pacientes lo presentaban a las 72h con ClCr medio de 186ml/min y el 56,52% presentaban HFG a las 168h de ingreso con ClCr medio de 207ml/min. Se encontró una relación positiva importante (p=0,07) entre la HFG manifestada a las 72h y a las 168h. Se observó relación estadísticamente significativa entre este fenómeno con edades más jóvenes, puntuaciones ISS más bajas y creatininas plasmáticas más bajas (AU)

Background and objective Augmented renal clearance or glomerular hyperfiltration (GHF) can significantly affect the clinical outcomes of renally eliminated drugs by promoting subtherapeutic drug exposure. The aggression suffered in patients who suffer severe trauma is a predisposition to manifest GHF and the identification of these patients remains a clinical challenge. The main objective of this study was to describe the prevalence of GHF in a cohort of critically ill trauma patients. Materials and methods Prospective observational study of a cohort of adult patients admitted after suffering severe trauma or polytrauma in the Anesthesiology ICU of the University Hospital of Albacete (Spain). Creatinine clearance (ClCr) was calculated in a 4-h urine collection sample at 24, 72 and 168h after admission applying the formula: CrCl: [diuresis in ml (urine/4h)×creatinine in urine (mg/dl)]÷[240 (min)×creatinine in plasma (mg/dl)]. A CrCl above 130ml/min was considered GHF. The analyzes were performed with the statistical software R version 4.0.4. Results Eighty-five patients were included. The median age of the patients was 51 years (IQR 26). Sixty-eight patients were male (78.82%). 75.29% of the patients were polytraumatized. Sixty-one patients (71.76%) presented GHF at some point in the CrCl determination. At 24h of admission, 56.34% of the patients presented GHF with a mean CrCl of 195.8ml/min, 61.11% of the patients presented it at 72h with a mean CrCl of 186ml/min and 56.52% presented GHF at 168h of admission with a mean CrCl of 207ml/min. A significant positive relationship (p=0.07) was found between GHF manifested at 72h and at 168h. We observed a statistically significant relationship between this phenomenon with younger ages, lower ISS scores and lower plasma creatinines (AU)

Arthroscopically Assisted Suprapatellar Tibial Nail Removal.

Intramedullary nailing remains the most popular and preferred method of fixation for tibial shaft fractures. The infrapatellar approach through the patellar tendon has long been considered the gold standard. However, the suprapatellar approach has gained popularity because of the advantages of being easier to perform when treating proximal shaft and metaphyseal fractures and there being less postoperative anterior knee pain. Despite increased use of this approach, the removal of the implant from the same suprapatellar approach is tricky, and in most cases, the removal is performed through a new transpatellar tendon approach. This article describes arthroscopically assisted suprapatellar tibial nail removal using the same approach and instrumentation of the nail insertion. The technique has the advantage of preserving the patellar tendon without causing secondary damage to it. Through arthroscopy, direct visualization of the patellofemoral joint aids in preventing possible cartilage injury. Moreover, any associated intra-articular lesions can be diagnosed and addressed.

Fibronectin-coated polyurethane meniscal scaffolding supplemented with MSCs improves scaffold integration and proteoglycan production in a rabbit model.

PURPOSE: The role of mesenchymal stem cells (MSC) in supporting the formation of new meniscal tissue in a meniscal scaffold is not well understood. The objective of this study was to assess the quality of the meniscal tissue produced in a fibronectin (FN)-coated polyurethane (PU) meniscal scaffold after a meniscal injury was made in an experimental rabbit model. METHODS: Twelve New Zealand white rabbits were divided in two groups after performing a medial meniscectomy of the anterior horn. In group 1, the meniscal defect was reconstructed with a non-MSC supplemented FN-coated PU scaffold. On the other hand, the same scaffold supplemented with MSCs was used in group 2. The animals were sacrificed at 12 week after index surgery. A modified scoring system was used for histological assessment. This new scoring (ranging from 0 to 15) includes a structural evaluation (meniscal scaffold interface and extracellular matrix production) and tissue quality evaluation (proteoglycan and type I-collagen content). RESULTS: The meniscal scaffold was found loose in the joint in three cases, corresponding to two cases in group 1 and 1 case in group 2. No differences were observed between the groups in terms of the total score (7.0 ± 0.9 vs. 9.4 ± 2.6, p = 0.09). However, differences were observed in group 2 in which 2 out of the 5 scored items, scaffold integration (1 ± 0.0 vs. 1.9 ± 0.6, p = 0.03) and proteoglycan production (1.2 ± 0.3 vs. 2.4 ± 0.2, p = 0.001). A trend to a higher production of Type I-Collagen production was also observed in group 2 (1.1 ± 0.4 vs. 1.4 ± 0.7, p = 0.05). CONCLUSION: In a rabbit model at 12 weeks, the adhesion of MSCs to a FN-coated PU scaffold improves scaffold integration, proteoglycan production and the characteristics of the new meniscal-like tissue obtained when compared to a non-supplemented scaffold. This fact could be a major step toward improving the adhesion of the MSCs to meniscal scaffolds and, consequently, the obtention of better quality meniscal tissue.

Defensive tolerance to parasitism is correlated with sexual selection in swallows.

Parasite-mediated sexual selection has been the topic of extensive research and enthusiastic debate for more than three decades. Here, we suggest that secondary sexual characters may not only signal parasite resistance but also defensive tolerance. We exemplify this possibility by analysing information on two sexually selected traits, annual reproductive success, and ectoparasitism in a barn swallow Hirundo rustica population followed for more than 30 years. For each individual, we estimated the slope of the association between reproductive success and parasitism as an index of tolerance and subsequently explored the association with the expression of the sexually selected traits. In accordance with expectations of parasites playing a role in sexual selection, tail length was negatively related to load of chewing lice and nest size was positively related to tolerance to chewing lice. We discuss the importance of considering defensive tolerance for understanding the role of parasite-mediated sexual selection.

Systematic lateral retinacular release does not reduce anterior knee pain after total knee arthroplasty with patellar resurfacing.

PURPOSE: The aim of this study was to assess the effect of systematic lateral retinacular release (LRR) on anterior knee pain (AKP), as well as its impact on the functional and radiological outcomes after total knee arthroplasty (TKA) with patellar resurfacing. METHODS: A prospective randomized study was designed. It included patients scheduled for a TKA procedure with patellar resurfacing, who were recruited and randomized into either the LRR group or the non-release group. 198 patients were included in the final analysis. The pressure pain threshold (PPT) assessed by pressure algometry (PA), the visual analogue scale (VAS), Feller's patellar score, the Knee Society Score (KSS), patellar height, and patellar tilt were recorded both preoperatively and at the 1-year follow-up. The Mann-Whitney U test was performed to determine comparisons between both groups as well as to determine differences' intragroup. RESULTS: Relative to the clinical variables and scores, no difference was detected between the two groups at the 1-year follow-up (p = n.s.). However, there was a slight difference in patellar tilt (0.1º vs. 1.4º, p = 0.044), with higher tilt values in the non-release group. There was no difference in terms of improvement in the clinical and radiological scores and variables recorded between the two groups (p = n.s.). CONCLUSION: LRR in primary TKA with patellar resurfacing does not show an improvement in AKP and functional outcomes over patellar resurfacing without release. LEVEL OF EVIDENCE: I.

Imaging of the Diabetic Foot.

Diabetic foot complications are increasingly prevalent in the world, leading to significant morbidity and driving up associated health care costs. Complex pathophysiology and suboptimal specificity of current imaging modalities have made diagnosis challenging, mainly in the evaluation of superimposed foot infection to underlying arthropathy or other marrow lesions. Recent advances in radiology and nuclear medicine have the potential to streamline the assessment of diabetic foot complications. But we must be aware of the specific strengths and weaknesses of each modality, and their applications. This review offers a comprehensive approach to the spectrum of diabetic foot complications and their imaging appearances in conventional and advanced imaging studies, including optimal technical considerations for each technique. Advanced magnetic resonance imaging (MRI) techniques are highlighted, illustrating their complementary role to conventional MRI, in particular their potential impact in avoiding additional studies.

A glimpse into relapsed refractory multiple myeloma treatment in real-world practice in Spain: the GeminiS study.

OBJECTIVES: To describe the incorporation of monoclonal antibodies (mAb) in real-world (RW) practice for the treatment of patients with relapsed refractory multiple myeloma (RRMM) in a setting with other treatment alternatives. METHODS: This was an observational, multicenter, ambispective study of RRMM treated with or without a mAb. RESULTS: A total of 171 patients were included. For the group treated without mAb, the median (95% CI) progression-free survival (PFS) to relapse was 22.4 (17.8-27.0) months; partial response or better (≥PR) and complete response or better (≥CR) was observed in 74.1% and 24.1% of patients, respectively; and median time to first response in first relapse was 2.0 months and in second relapse was 2.5 months. For the group of patients treated with mAb in first or second relapse, the median PFS was 20.9 (95% CI, could not be evaluated) months; the ≥ PR and ≥ CR rates were 76,2% and 28.6%, respectively; and the median time to first response in first relapse was 1.2 month and in second relapse was 1.0 months. The safety profiles for the combinations were consistent with those expected. CONCLUSIONS: The incorporation of mAb in RW practice for the treatment of RRMM has shown good quality and speed of response with a similar safety profile shown in randomized clinical trials.

Clinical relevance of timing of assessment of ICU mortality in patients with moderate-to-severe Acute Respiratory Distress Syndrome.

Mortality is a frequently reported outcome in clinical studies of acute respiratory distress syndrome (ARDS). However, timing of mortality assessment has not been well characterized. We aimed to identify a crossing-point between cumulative survival and death in the intensive care unit (ICU) of patients with moderate-to-severe ARDS, beyond which the number of survivors would exceed the number of deaths. We hypothesized that this intersection would occur earlier in a successful clinical trial vs. observational studies of moderate/severe ARDS and predict treatment response. We conducted an ancillary study of 1580 patients with moderate-to-severe ARDS managed with lung-protective ventilation to assess the relevance and timing of measuring ICU mortality rates at different time-points during ICU stay. First, we analyzed 1303 patients from four multicenter, observational cohorts enrolling consecutive patients with moderate/severe ARDS. We assessed cumulative ICU survival from the time of moderate/severe ARDS diagnosis to ventilatory support discontinuation within 7-days, 28-days, 60-days, and at ICU discharge. Then, we compared these findings to those of a successful randomized trial of 277 moderate/severe ARDS patients. In the observational cohorts, ICU mortality (487/1303, 37.4%) and 28-day mortality (425/1102, 38.6%) were similar (p = 0.549). Cumulative proportion of ICU survivors and non-survivors crossed at day-7; after day-7, the number of ICU survivors was progressively higher compared to non-survivors. Measures of oxygenation, lung mechanics, and severity scores were different between survivors and non-survivors at each point-in-time (p < 0.001). In the trial cohort, the cumulative proportion of survivors and non-survivors in the treatment group crossed before day-3 after diagnosis of moderate/severe ARDS. In clinical ARDS studies, 28-day mortality closely approximates and may be used as a surrogate for ICU mortality. For patients with moderate-to-severe ARDS, ICU mortality assessment within the first week of a trial might be an early predictor of treatment response.

Geriatric assessment in hematology scale predicts treatment tolerability in older patients diagnosed with hematological malignancies: The RETROGAH study.

INTRODUCTION: The GAH (Geriatric Assessment in Hematology) scale is a psychometrically valid tool aimed at identifying older patients with hematological malignancies at higher risk of treatment-related toxicity. Our objective in this study was to determine the weights for each dimension of the GAH scale and the cut-off point to reliably predict treatment tolerability in this population, estimated by a weighted receiver operating characteristic (ROC) analysis and quantified by the area under the curve (AUC). MATERIAL AND METHODS: The RETROGAH was a retrospective cohort study including 126 patients who had previously participated in the GAH study. Patients were ≥ 65 years old with newly diagnosed myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML), multiple myeloma (MM), or chronic lymphoid leukemia (CLL) and treated with standard front-line therapy within three months after having completed the GAH scale. RESULTS: The optimal cut-off value of the GAH total score to discriminate patients at higher risk of treatment toxicity was 42, with 68.5% sensitivity and 55.8% specificity. Using this value, 66.1% of patients evaluated were found to develop some type of toxicity. The AUC was 0.6259 (95% CI: 0.512-0.739; p = 0.035). DISCUSSION: The GAH scale not only would enable clinicians to individualize therapy based on individual risk of toxicity but also discriminate patients that will benefit most from intensive treatments from those requiring an adapted approach. While futures studies in clinical practice may improve the model and overcome its limitations, the GAH scale should not be used alone when making treatment decisions.

Mini-invasive approach vs. traditional open reduction for periprosthetic hip fracture osteosynthesis with the NCB® plate.

BACKGROUND: Postoperative hip periprosthetic fracture (PPF) is a frequent complication whose treatment does not achieve optimal results among eldery fragile patients. Locking compression plate (LCP) osteosynthesis is the gold standard treatment for Vancouver B1 and VC fractures and there is a growing consensus in doing the same with B2 fractures in patients with high comorbidity. Following that trend of being as non-aggressive as possible we investigated whether a mini-open (MO) approach would lead to better outcomes in LCP plate osteosynthesis of hip PFFs when compared to the traditional open approach. METHODS: We retrospectively evaluated a cohort of 43 VB1, VB2 or VC hip PPFs treated with non contact bridging (NCB®) plate osteosynthesis by two possible approaches. MO vs traditional open approach. The main objective was to assess whether MO approach decreases operative time, bleeding and local complications. The secondary objective was to demonstrate that this may have a positive effect on patient function. RESULTS: The mean age was 79.6 years old and 74.5% patients had an ASA score of III or IV. The surgical time was 148.53 min (SD 33.2) in the open approach versus 107.42 min (SD 25.6) in the MO, which was 31 min shorter (p<0.001). Hemoglobin dropped 0.9 points less, on average (p. 0.005) and 0.82 fewer blood concentrates were required (p. 0.022) with MO approach. There were no differences among complications but there was a trend towards greater independence and better mobility in the MO approach group with a postoperative Barthel of 74.37 (sd. 13.21) compared to the 66.67 points (sd. 13.7) in the traditional approach group. CONCLUSION: MO approach in osteosynthesis of hip PFFs decreases operative time and intraoperative bleeding so it must be considered in fragile patients with high comorbidity.