Impact of coadministration of proton-pump inhibitors and palbociclib in hormone receptor-positive/HER2-negative advanced breast cancer.

BACKGROUND: The capsule formulation of CDK4/6 inhibitor palbociclib has reduced solubility at gastric pH > 4.5 and may have decreased activity when used with proton-pump inhibitors (PPI). Herein, we report the effect of PPI on palbociclib capsule activity and safety in the PARSIFAL study. METHODS: First-line endocrine-sensitive, hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) patients received palbociclib capsules plus fulvestrant or letrozole. The primary endpoint was progression-free survival (PFS). This post-hoc analysis compared PPI use. Patients were PPI-naïve (N-PPI) if not on PPI during the study, and either early (E-PPI) or long-term PPI (LT-PPI) if on PPI at study entry or for at least ≥⅔ of treatment, respectively. PPI groups were not mutually exclusive. RESULTS: Among 486 patients, 66.9 % were N-PPI, 13.2 % E-PPI, 18.7 % LT-PPI, and 11.5 % of the PPI users were defined as neither. Median PFS (mPFS) was 29.6 months in the study population, 28.7 months in N-PPI, 23.0 months in E-PPI (Hazard Ratio [HR] 1.5; 95%Confidence Interval [CI] 1.1-2.2; p = 0.024), and 23.0 months in LT-PPI (HR 1.4; 95%CI 1.0-1.9; p = 0.035). By landmark analysis, PPI use was associated with poorer mPFS at 3 and 12 months. Grade ≥3 hematological adverse events occurred in 71.7 % of N-PPI, 57.8 % of E-PPI (p = 0.021), and 54.9 % of LT-PPI (p = 0.003). Dose reductions and dosing delays due to hematological toxicity occurred in 70.8 % of N-PPI, 56.3 % of E-PPI (p = 0.018), and 52.7 % of LT-PPI (p = 0.002). CONCLUSIONS: PPI use may reduce palbociclib capsule toxicity, dose modifications, and clinical activity in HR+/HER2- ABC.

Genotyping Hepatitis B virus by Next-Generation Sequencing: Detection of Mixed Infections and Analysis of Sequence Conservation.

Our aim was to develop an accurate, highly sensitive method for HBV genotype determination and detection of genotype mixtures. We examined the preS and 5' end of the HBV X gene (5X) regions of the HBV genome using next-generation sequencing (NGS). The 1852 haplotypes obtained were subjected to genotyping via the Distance-Based discrimination method (DB Rule) using two sets of 95 reference sequences of genotypes A-H. In clinical samples from 125 patients, the main genotypes were A, D, F and H in Caucasian, B and C in Asian and A and E in Sub-Saharan patients. Genotype mixtures were identified in 28 (22.40%) cases, and potential intergenotypic recombination was observed in 29 (23.20%) cases. Furthermore, we evaluated sequence conservation among haplotypes classified into genotypes A, C, D, and E by computing the information content. The preS haplotypes exhibited limited shared conserved regions, whereas the 5X haplotypes revealed two groups of conserved regions across the genotypes assessed. In conclusion, we developed an NGS-based HBV genotyping method utilizing the DB Rule for genotype classification. We identified two regions conserved across different genotypes at 5X, offering promising targets for RNA interference-based antiviral therapies.

Cell-free assays reveal the HIV-1 capsid protects reverse transcripts from cGAS.

Retroviruses can be detected by the innate immune sensor cyclic GMP-AMP synthase (cGAS), which recognizes reverse-transcribed DNA and activates an antiviral response. However, the extent to which HIV-1 shields its genome from cGAS recognition remains unclear. To study this process in mechanistic detail, we reconstituted reverse transcription, genome release, and innate immune sensing of HIV-1 in a cell-free system. We found that wild-type HIV-1 capsids protect their genomes from cGAS even after completion of reverse transcription. Viral DNA could be "deprotected" by thermal stress, capsid mutations, or reduced concentrations of inositol hexakisphosphate (IP6) that destabilize the capsid. Strikingly, capsid inhibitors also disrupted viral cores and dramatically potentiated cGAS activity, both in vitro and in cellular infections. Our results provide biochemical evidence that the HIV-1 capsid lattice conceals the genome from cGAS and that chemical or physical disruption of the viral core can expose HIV-1 DNA and activate innate immune signaling.

NLRP3 and AIM2 inflammasomes exacerbate the pathogenic Th17 cell response to eggs of the helminth Schistosoma mansoni.

Infection with the helminth Schistosoma mansoni can cause exacerbated morbidity and mortality via a pathogenic host CD4 T cell-mediated immune response directed against parasite egg antigens, with T helper (Th) 17 cells playing a major role in the development of severe granulomatous hepatic immunopathology. The role of inflammasomes in intensifying disease has been reported; however, neither the types of caspases and inflammasomes involved, nor their impact on the Th17 response are known. Here we show that enhanced egg-induced IL-1ß secretion and pyroptotic cell death required both caspase-1 and caspase-8 as well as NLRP3 and AIM2 inflammasome activation. Schistosome genomic DNA activated AIM2, whereas reactive oxygen species, potassium efflux and cathepsin B, were the major activators of NLRP3. NLRP3 and AIM2 deficiency led to a significant reduction in pathogenic Th17 responses, suggesting their crucial and non-redundant role in promoting inflammation. Additionally, we show that NLRP3- and AIM2-induced IL-1ß suppressed IL-4 and protective Type I IFN (IFN-I) production, which further enhanced inflammation. IFN-I signaling also curbed inflammasome- mediated IL-1ß production suggesting that these two antagonistic pathways shape the severity of disease. Lastly, Gasdermin D (Gsdmd) deficiency resulted in a marked decrease in egg-induced granulomatous inflammation. Our findings establish NLRP3/AIM2-Gsdmd axis as a central inducer of pathogenic Th17 responses which is counteracted by IFN-I pathway in schistosomiasis.

The genomic profiling of high-risk smoldering myeloma patients treated with an intensive strategy unveils potential markers of resistance and progression.

Smoldering multiple myeloma (SMM) precedes multiple myeloma (MM). The risk of progression of SMM patients is not uniform, thus different progression-risk models have been developed, although they are mainly based on clinical parameters. Recently, genomic predictors of progression have been defined for untreated SMM. However, the usefulness of such markers in the context of clinical trials evaluating upfront treatment in high-risk SMM (HR SMM) has not been explored yet, precluding the identification of baseline genomic alterations leading to drug resistance. For this reason, we carried out next-generation sequencing and fluorescent in-situ hybridization studies on 57 HR and ultra-high risk (UHR) SMM patients treated in the phase II GEM-CESAR clinical trial (NCT02415413). DIS3, FAM46C, and FGFR3 mutations, as well as t(4;14) and 1q alterations, were enriched in HR SMM. TRAF3 mutations were specifically associated with UHR SMM but identified cases with improved outcomes. Importantly, novel potential predictors of treatment resistance were identified: NRAS mutations and the co-occurrence of t(4;14) plus FGFR3 mutations were associated with an increased risk of biological progression. In conclusion, we have carried out for the first time a molecular characterization of HR SMM patients treated with an intensive regimen, identifying genomic predictors of poor outcomes in this setting.

Prediction of the univariant two-phase coexistence line of the tetrahydrofuran hydrate from computer simulation.

In this work, the univariant two-phase coexistence line of the tetrahydrofuran (THF) hydrate is determined from 100 to 1000 bar by molecular dynamics simulations. This study is carried out by putting in contact a THF hydrate phase with a stoichiometric aqueous solution phase. Following the direct coexistence technique, the pressure is fixed, and the coexistence line is determined by analyzing if the hydrate phase grows or melts at different values of temperature. Water is described using the well-known TIP4P/Ice model. We have used two different models of THF based on the transferable parameters for phase equilibria-united atom approach (TraPPE-UA), the original (flexible) TraPPe-UA model and a rigid and planar version of it. Overall, at high pressures, small differences are observed in the results obtained by both models. However, large differences are observed in the computational efforts required by the simulations performed using both models, being the rigid and planar version much faster than the original one. The effect of the unlike dispersive interactions between the water and THF molecules is also analyzed at 250 bar using the rigid and planar THF model. In particular, we modify the Berthelot combining rule via a parameter ξO-THF that controls the unlike water-THF dispersive interactions. We analyze the effect on the dissociation temperature of the hydrate when ξO-THF is modified from 1.0 (original Berthelot combining rule) to 1.4 (modified Berthelot combining rule). We use the optimized value ξO-THF = 1.4 and the rigid THF model in a transferable way to predict the dissociation temperatures at other pressures. We find excellent agreement between computer simulation predictions and experimental data taken from the literature.

Diagnosis and management of urinary bladder paragangliomas: A Sino-American-European retrospective observational study.

OBJECTIVE: Paragangliomas of the urinary bladder (UBPGLs) are rare neuroendocrine tumours and pose a diagnostic and surgical challenge. It remains unclear what factors contribute to a timely presurgical diagnosis. The purpose of this study is to identify factors contributing to missing the diagnosis of UBPGLs before surgery. DESIGN, PATIENTS AND MEASUREMENTS: A total of 73 patients from 11 centres in China, and 51 patients from 6 centres in Europe and 1 center in the United States were included. Clinical, surgical and genetic data were collected and compared in patients diagnosed before versus after surgery. Logistic regression analysis was used to identify clinical factors associated with initiation of presurgical biochemical testing. RESULTS: Among all patients, only 47.6% were diagnosed before surgery. These patients were younger (34.0 vs. 54.0 years, p < .001), had larger tumours (2.9 vs. 1.8 cm, p < .001), and more had a SDHB pathogenic variant (54.7% vs. 11.9%, p < .001) than those diagnosed after surgery. Patients with presurgical diagnosis presented with more micturition spells (39.7% vs. 15.9%, p = .003), hypertension (50.0% vs. 31.7%, p = .041) and catecholamine-related symptoms (37.9% vs. 17.5%, p = .012). Multivariable logistic analysis revealed that presence of younger age (<35 years, odds ratio [OR] = 6.47, p = .013), micturition spells (OR = 6.79, p = .007), hypertension (OR = 3.98, p = .011), and sweating (OR = 41.72, p = .013) increased the probability of initiating presurgical biochemical testing. CONCLUSIONS: Most patients with UBPGL are diagnosed after surgery. Young age, hypertension, micturition spells and sweating are clues in assisting to initiate early biochemical testing and thus may establish a timely presurgical diagnosis.

Genetically Predicted Body Mass Index and Mortality in COPD.

RATIONALE: BMI is associated with COPD mortality, but the underlying mechanisms are unclear. The effect of genetic variants aggregated into a polygenic score may elucidate causal mechanisms and predict risk. OBJECTIVES: To examine the associations of genetically predicted BMI with all-cause and cause-specific mortality in COPD. METHODS: We developed a polygenic score for BMI (PGSBMI) and tested for associations of the PGSBMI with all-cause, respiratory, and cardiovascular mortality in participants with COPD from the COPDGene, ECLIPSE, and Framingham Heart studies. We calculated the difference between measured BMI and PGS-predicted BMI (BMIdiff) and categorized participants into groups of discordantly low (BMIdiff < 20th percentile), concordant (BMIdiff between 20th - 80th percentile), and discordantly high (BMIdiff > 80th percentile) BMI. We applied Cox models, examined potential non-linear associations of the PGSBMI and BMIdiff with mortality, and summarized results with meta-analysis. MEASUREMENTS AND MAIN RESULTS: We observed significant non-linear associations of measured BMI and BMIdiff, but not PGSBMI, with all-cause mortality. In meta-analyses, a one standard deviation increase in the PGSBMI was associated with an increased hazard for cardiovascular mortality (HR=1.29, 95% CI=1.12-1.49), but not with respiratory or all-cause mortality. Compared to participants with concordant measured and genetically predicted BMI, those with discordantly low BMI had higher mortality risk for all-cause (HR=1.57, CI=1.41-1.74) and respiratory death (HR=2.01, CI=1.61-2.51). CONCLUSIONS: In people with COPD, higher genetically predicted BMI is associated with higher cardiovascular mortality but not respiratory mortality. Individuals with discordantly low BMI have higher all-cause and respiratory mortality compared to those with concordant BMI.

Assessing viral metagenomics for the diagnosis of acute undifferentiated fever in returned travellers: a multicenter cohort study.

BACKGROUND: Up to 45% of febrile returning travellers remain undiagnosed after a thorough diagnostic work-up, even at referral centres. Although metagenomic next-generation sequencing (mNGS) has emerged as a promising tool, evidence of its usefulness in imported fever is very limited. METHODS: Travellers returning with fever were prospectively recruited in three referral clinics from November 2017 to November 2019. Unbiased mNGS optimised for virus detection was performed on serum samples of participants with acute undifferentiated febrile illness (AUFI), and results were compared to those obtained by reference diagnostic methods (RDM). RESULTS: Among 507 returned febrile travellers, 433(85.4%) presented with AUFI. Dengue virus (n = 86) and Plasmodium spp. (n = 83) were the most common causes of fever. 103/433(23.8%) AUFI remained undiagnosed at the end of the follow-up.Metagenomic next-generation sequencing unveiled potentially pathogenic microorganisms in 196/433(38.7%) AUFI. mNGS identifications were more common in patients with a shorter duration of fever (42.3% in ≤5 days vs 28.7% in >5 days, P = 0.005). Potential causes of fever were revealed in 25/103(24.2%) undiagnosed AUFI and 5/23(21.7%) travellers with severe undiagnosed AUFI. Missed severe aetiologies included eight bacterial identifications and one co-infection of B19 parvovirus and Aspergillus spp.Additional identifications indicating possible co-infections occurred in 29/316(9.2%) travellers with AUFI, and in 11/128(8.6%) travellers with severe AUFI, who had received a diagnosis through RDM. The most common co-infections detected in severe AUFI were caused by Gram-negative bacteria. Serum mNGS was unable to detect >50% of infectious diagnoses achieved by RDM and also yielded 607 non-pathogenic identifications. DISCUSSION: mNGS of serum can be a valuable diagnostic tool for selected travellers with undiagnosed AUFI or severe disease in addition to reference diagnostic techniques, especially during the first days of symptoms. Nevertheless, mNGS results interpretation presents a great challenge. Further studies evaluating the performance of mNGS using different sample types and protocols tailored to non-viral agents are needed.

Diagnosis of multiple sclerosis using optical coherence tomography supported by explainable artificial intelligence.

BACKGROUND/OBJECTIVES: Study of retinal structure based on optical coherence tomography (OCT) data can facilitate early diagnosis of relapsing-remitting multiple sclerosis (RRMS). Although artificial intelligence can provide highly reliable diagnoses, the results obtained must be explainable. SUBJECTS/METHODS: The study included 79 recently diagnosed RRMS patients and 69 age matched healthy control subjects. Thickness (Avg) and inter-eye difference (Diff) features are obtained in 4 retinal layers using the posterior pole protocol. Each layer is divided into six analysis zones. The Support Vector Machine plus Recursive Feature Elimination with Leave-One-Out Cross Validation (SVM-RFE-LOOCV) approach is used to find the subset of features that reduces dimensionality and optimises the performance of the classifier. RESULTS: SVM-RFE-LOOCV was used to identify OCT features with greatest capacity for early diagnosis, determining the area of the papillomacular bundle to be the most influential. A correlation was observed between loss of layer thickness and increase in functional disability. There was also greater functional deterioration in patients with greater asymmetry between left and right eyes. The classifier based on the top-ranked features obtained sensitivity = 0.86 and specificity = 0.90. CONCLUSIONS: There was consistency between the features identified as relevant by the SVM-RFE-LOOCV approach and the retinotopic distribution of the retinal nerve fibres and the optic nerve head. This simple method contributes to implementation of an assisted diagnosis system and its accuracy exceeds that achieved with magnetic resonance imaging of the central nervous system, the current gold standard. This paper provides novel insights into RRMS affectation of the neuroretina.

Senile Cataract Formation Does Not Affect Crystalline Lens Thickness.

INTRODUCTION: Characterizing lens thickness (LT) in patients with cataracts is important for better understanding the lens aging process and for designing new intraocular lens power formulas. This study aimed to analyze the influence of common senile cataract formation on the LT, anterior (ACS) and posterior (PCS) cortex space, and nuclear thickness (NT), controlling for sex, age, and axial length. METHODS: A cross-sectional study was performed. A consecutive sample of 603 volunteers (403 women, 200 men) aged 59.1 ± 18.8 years was recruited. The standardized Lens Opacification Classification System (LOCS)-III was used to classify eyes (randomly selected) into cataractous and non-cataractous groups. Also, they were classified according to the cataract location (presence or absence of cortical, nuclear, or posterior subcapsular cataract). Optical biometry was performed to measure LT, ACS, NT, and PCS. Propensity score was used to match participants one-to-one for sex, age, and axial length. Groups were compared using the Student's t test or Yuen's test. RESULTS: The four classifications divided unmatched eyes into: 361 cataractous lenses and 242 non-cataractous, 226 cortical and 377 non-cortical cataractous, 313 nuclear and 290 non-nuclear cataractous and 242 subcapsular and 361 non-subcapsular cataractous. Before matching, cataractous eyes showed significantly higher LT (4.52 ± 0.39 vs. 3.94 ± 0.46 mm, p < 0.001), ACS (0.75 ± 0.20 vs. 0.58 ± 0.23 mm, p < 0.001), NT (3.34 ± 0.23 vs. 3.18 ± 0.25 mm, p < 0.001) and PCS (0.42 ± 0.19 vs. 0.37 ± 0.19 mm, p = 0.003). Matched lens, cortical, nuclear, and subcapsular cataract samples comprised 146, 258, 182, and 226 eyes, respectively. After matching, no significant differences were observed in LT (4.34 ± 0.37 vs. 4.33 ± 0.36 mm, p = 0.94), ACS (0.72 ± 0.20 vs. 0.76 ± 0.19 mm, p = 0.08), NT (3.31 ± 0.22 vs. 3.30 ± 0.23 mm, p = 0.24) and PCS (0.42 ± 0.19 vs. 0.43 ± 0.16 mm, p = 0.79). CONCLUSIONS: The presence of senile cortical, nuclear, and posterior subcapsular cataract have no effect on LT, ACS, NT, and PCS. Confounding factors should be controlled for when measuring LT and its main components.

Implications of Mean Pulmonary Arterial Wedge Pressure Trajectories in Pulmonary Arterial Hypertension.

Rationale: The mean pulmonary arterial wedge pressure (mPAWP) is the critical hemodynamic factor differentiating group 1 pulmonary arterial hypertension (PAH) from group 2 pulmonary hypertension associated with left heart disease. Despite the discrepancy between the mPAWP upper physiologic normal and current PAH definitions, the implications of the initial mPAWP for PAH clinical trajectory are poorly understood. Objectives: To model longitudinal mPAWP trajectories in PAH over 10 years and examine the clinical and hemodynamic factors associated with trajectory membership. Methods: Adult patients with PAH with two or more right heart catheterizations were identified from a multiinstitution healthcare system in eastern Massachusetts. mPAWP trajectories were constructed via group-based trajectory modeling. Feature selection was performed in least absolute shrinkage and selection operator regression. Logistic regression was used to assess associations between trajectory membership, baseline characteristics, and transplant-free survival. Measurements and Main Results: Among 301 patients with PAH, there were two distinct mPAWP trajectories, termed "mPAWP-high" (n = 71; 23.6%) and "mPAWP-low" (n = 230; 76.4%), based on the ultimate mPAWP value. Initial mPAWP clustered around median 12 mm Hg (interquartile range [IQR], 8-14 mm Hg) in the mPAWP-high and 9 mm Hg (IQR, 6-11 mm Hg) in the mPAWP-low trajectories (P < 0.001). After feature selection, initial mPAWP ⩾12 mm Hg predicted an mPAWP-high trajectory (odds ratio, 3.2; 95% confidence interval, 1.4-6.1; P = 0.0006). An mPAWP-high trajectory was associated with shorter transplant-free survival (vs. mPAWP-low, median, 7.8 vs. 11.3 yr; log-rank P = 0.017; age-adjusted P = 0.217). Conclusions: Over 10 years, the mPAWP followed two distinct trajectories, with 25% evolving into group 2 pulmonary hypertension physiology. Using routine baseline data, longitudinal mPAWP trajectory could be predicted accurately, with initial mPAWP ⩾12 mm Hg as one of the strongest predictors.

Dissociation line and driving force for nucleation of the nitrogen hydrate from computer simulation.

In this work, we determine the dissociation line of the nitrogen (N2) hydrate by computer simulation using the TIP4P/Ice model for water and the TraPPE force field for N2. We use the solubility method proposed recently by some of us to evaluate the dissociation temperature of the hydrate at different pressures, from 500 to 1500 bar. Particularly, we calculate the solubility of N2 in the aqueous solution when it is in contact with a N2-rich liquid phase and when in contact with the hydrate phase via planar interfaces as functions of temperature. Since the solubility of N2 decreases with temperature in the first case and increases with temperature in the second case, both curves intersect at a certain temperature that determines the dissociation temperature at a given pressure. We find a good agreement between the predictions obtained in this work and the experimental data taken from the literature in the range of pressures considered in this work. From our knowledge of the solubility curves of N2 in the aqueous solution, we also determine the driving force for nucleation of the hydrate, as a function of temperature, at different pressures. In particular, we use two different thermodynamic routes to evaluate the change in chemical potential for hydrate formation. Although the driving force for nucleation slightly decreases (in absolute value) when the pressure is increased, our results indicate that the effect of pressure can be considered negligible in the range of pressures studied in this work. To the best of our knowledge, this is the first time the driving force for nucleation of a hydrate that exhibits crystallographic structure sII, along its dissociation line, is studied from computer simulation.

The imperative for quality control programs in Monkeypox virus DNA testing by PCR: CIBERINFEC quality control.

To evaluate molecular assays for Mpox diagnosis available in various clinical microbiology services in Spain through a quality control (QC) approach. A total of 14 centers from across Spain participated in the study. The Reference Laboratory dispatched eight serum samples and eight nucleic acid extracts to each participating center. Some samples were spiked with Mpox or Vaccinia virus to mimic positive samples for Mpox or other orthopox viruses. Participating centers provided information on the results obtained, as well as the laboratory methods used. Among the 14 participating centers seven different commercial assays were employed, with the most commonly used kit being LightMix Modular Orthopox/Monkeypox (Mpox) Virus (Roche®). Of the 12 centers conducting Mpox determinations, concordance ranged from 62.5% (n = 1) to 100% (n = 11) for eluates and from 75.0% (n = 1) to 100% (n = 10) for serum. Among the 10 centers performing Orthopoxvirus determinations, a 100% concordance was observed for eluates, while for serum, concordance ranged from 87.5% (n = 6) to 100% (n = 4). Repeatedly, 6 different centers reported a false negative in serum samples for Orthopoxvirus diagnosis, particularly in a sample with borderline Ct = 39. Conversely, one center, using the TaqMan™ Mpox Virus Microbe Detection Assay (Thermo Fisher), reported false positives in Mpox diagnosis for samples spiked with vaccinia virus due to cross-reactions. We observed a positive correlation of various diagnostic assays for Mpox used by the participating centers with the reference values. Our results highlight the significance of standardization, validation, and ongoing QC in the microbiological diagnosis of infectious diseases, which might be particularly relevant for emerging viruses.

Hablando at home: Examining the interactional resources of a bilingual autistic child.

Daily language interactions predict child outcomes. For multilingual families who rear neurodiverse children and who may be minoritized for their language use, a dearth of research examines families' daily language interactions. Utilizing a language socialization framework and a case study methodology, 4,991 English and Spanish utterances from a 5-year old autistic child and his family were collected during naturally occurring interactions over 10 days. Utterances were analyzed for patterns of code-switching by speaker, activity setting, English or Spanish initial language, and code-switch function. Spanish was spoken in most activities. For reading, both languages were equally employed by the father. While participants used both languages across all activity settings, significant variations in code-switching type and function were observed by activity setting and speaker. We discuss implications for how home language resources can be integrated into autism interventions.

Increase in Postoperative Body Mass Index in Patients After Total Knee Arthroplasty.

Objectives The aim of this is to investigate the changes in body mass index (BMI) following knee arthroplasty and to evaluate their impact on patient-reported outcomes and functional evaluations. Methods This observational study included 90 patients who underwent total knee arthroplasty (TKA) and were followed up for a median period of 2.6 years. BMI measurements were recorded before and after surgery, and patient-reported outcomes and functional evaluations were assessed using standardized scales and tests. Results Following TKA, BMI increased statistically significantly (Wilcoxon signed-rank test, p < 0.000). In addition, half of the patients experienced an increase in BMI, with 32% moving up in their BMI category. However, there were no clinically significant differences in patient-reported outcomes or functional evaluations between the group that gained BMI and the group that maintained or lost BMI. Conclusion This study reveals that patients tend to have increased BMI following TKA. However, these BMI changes do not significantly impact patient-reported outcomes or functional evaluations. It underscores the importance of patient education regarding healthy lifestyle habits, including diet and physical activity, to address postoperative weight gain effectively.

[Bilateral central femoral dislocation after seizure. Antiprotrusive ring and dual mobility cup as a therapeutic option. Apropos of a case]. / Luxación bilateral central femoral tras crisis convulsiva. Anillo antiprotrusivo y cotilo de doble movilidad como opción terapéutica. A propósito de un caso.

INTRODUCTION: seizures can trigger fractures and dislocations. Injuries depend on the severity, duration and type of seizure. We present a case report of a male patient who presented with a bilateral central dislocation fracture of the hip following an episode of seizure. A case rarely described in the literature with complex and unusual management. CASE REPORT: a 77-year-old man with a history of moderate cognitive impairment suffered a bilateral central dislocation of the hip in the context of a generalized epileptic seizure. Clinically on arrival at the emergency department, the patient presented shortening of the right lower extremity compared to the contralateral, external rotation and joint locking on log roll test in both extremities. An imaging study and clinical optimization were performed prior to surgery. It was performed in two stages. First the left hip on the 8th day of admission, and the right hip on the 15th. In both surgeries the same procedure was performed, with implantation of an antiprotrusive ring and a double mobility cup prosthesis with an uncemented femoral stem. In the immediate postoperative period, the patient did not present any complications associated with the surgery. At 24-month follow-up, the patient performed full weight bearing with a Harris hip score (HHS) of 77 on the right hip and 79 on the left; 12 points on the WOMAC scale. No postoperative complications have occurred so far. CONCLUSIONS: these injuries are uncommon in our daily practice, where multiple options are available to address them. In our patient, the use of arthroplasty and antiprotrusive rings offers advantages over fracture synthesis techniques, such as early mobilization with moderate functional results and few postoperative complications.

INTRODUCCIÓN: las crisis convulsivas pueden desencadenar fracturas y luxaciones. Las lesiones dependen de la severidad, duración y el tipo de crisis. Presentamos un caso clínico de un varón que presentó una fractura luxación central bilateral de cadera tras episodio de crisis convulsiva. Un caso pocas veces descrito en la literatura con un manejo complejo y poco habitual. CASO CLÍNICO: paciente de 77 años con antecedentes de deterioro cognitivo moderado que sufrió una luxación bilateral central de cadera en contexto de una crisis convulsiva generalizada. Clínicamente, a su llegada a urgencias, el paciente presentaba un acortamiento de la extremidad inferior derecha en comparación con la contralateral, rotación externa y bloqueo articular a la realización del log roll test en ambas extremidades. Se realizó estudio de imagen y optimización clínica previo a cirugía. Se realizó en dos tiempos: primero la cadera izquierda al octavo día de ingreso y la cadera derecha al decimoquinto. En ambas cirugías se realizó el mismo procedimiento mediante implantación de anillo antiprotrusivo y prótesis con cotilo de doble movilidad con vástago femoral no cementado. En el postoperatorio inmediato, el paciente no presentó ninguna complicación asociada a la cirugía. En el seguimiento a los 12 meses, el paciente realiza carga completa con un Harris hip score (HHS) de 77 cadera derecha y 79 en la izquierda; 12 puntos en la escala WOMAC. No ha presentado complicaciones postoperatorias hasta el momento. CONCLUSIONES: estas lesiones son poco comunes en nuestra práctica diaria, donde disponemos de múltiples opciones para abordarlas. En nuestro paciente, el empleo de la artroplastía y de anillos antiprotrusivos nos ofrecen ventajas respecto a las técnicas de síntesis de la fractura, como una movilización precoz y evitar desarrollo prematuro de una artrosis postraumática, con resultados buenos, funcionales y pocas complicaciones postoperatorias.

Environmental risk assessment of PPP application in European soils and potential ecosystem service losses considering impacts on non-target organisms.

The use of Plant Protection Products (PPPs) is leading to high exposure scenarios with potential risk to soil organisms, including non-target species. Assessment of the effects of PPPs on non-target organisms is one of the most important components of environmental risk assessment (ERA) since they play crucial functions in ecosystems, being main driving forces in different soil processes. As part of the framework, EFSA is proposing the use of the ecosystem services approach for setting specific protection goals. In fact, the services provided by soil organisms can be impacted by the misuse of PPPs in agroecosystems. The aim of this work was to assess PPPs potential risk upon ecosystem services along European soils, considering impacts on earthworms and collembola. Four well-known (2 insecticides-esfenvalerate and cyclaniliprole- and 2 fungicides - picoxystrobin and fenamidone-) worst case application (highest recommended application) were studied; exploring approaches for linked observed effects with impacts on ecosystem services, accounting for their mode of action (MoA), predicted exposure, time-course effects in Eisenia fetida and Folsomia sp. and landscape variability. The selected fungicides exerted more effects than insecticides on E. fetida, whereas few effects were reported for both pesticides regarding Folsomia sp. The most impacted ecosystem services after PPP application to crops appeared to be habitat provision, soil formation and retention, nutrient cycling, biodiversity, erosion regulation, soil remediation/waste treatment and pest and disease regulation. The main factors to be taken into account for a correct PPP use management in crops are discussed.