Early estimates of nirsevimab immunoprophylaxis effectiveness against hospital admission for respiratory syncytial virus lower respiratory tract infections in infants, Spain, October 2023 to January 2024.

The monoclonal antibody nirsevimab was at least 70% effective in preventing hospitalisations in infants with lower respiratory tract infections (LRTI) positive for respiratory syncytial virus (RSV) in Spain (Oct 2023-Jan 2024), where a universal immunisation programme began late September (coverage range: 79-99%). High protection was confirmed by two methodological designs (screening and test-negative) in a multicentre active surveillance in nine hospitals in three regions. No protection against RSV-negative LRTI-hospitalisations was shown. These interim results could guide public-health decision-making.

Parascapular Flap for Severe Hidradenitis Suppurativa.

Hidradenitis suppurativa is a chronic inflammatory disease which affects apocrine glands and hair follicles of the skin, primarily in the axillary and groin regions. This condition can be highly debilitating, causing painful lesions and a negative psychological impact on patients. While medical and minimally invasive treatments are available, surgical intervention may be necessary for severe cases. In cases involving axillary defects, the use of local flaps such as the parascapular flap is a viable option. In this case report, we present a 34-year-old woman who presented to our clinic with a history of recurrent abscesses and cutaneous infections in the axillary region. After thorough evaluation, we chose to use the parascapular flap for reconstruction. The parascapular flap is a one-stage procedure that allows for extensive resection of the axillary area without resulting in contractions or retractions over the long term. Additionally, this technique allows for preservation of the axilla's original shape with minimal donor site morbidity.

Impact of a Hospitalist Co-Management Program on Medical Complications and Length of Stay in Neurosurgical Patients.

BACKGROUND: The impact of co-management on clinical outcomes in neurosurgical patients is uncertain. This study aims to describe the implementation of a hospitalist co-management program in a neurosurgery department and its impact on the incidence of complications, mortality, and length of stay. METHODS: The authors used a quasi-experimental study design that compared a historical control period (July-December 2017) to a prospective intervention arm. During the intervention period, patients admitted to a neurosurgery inpatient unit who were older than 65 years, suffered certain conditions, or were admitted from ICUs were included in the co-management program. Two hospitalists joined the surgical staff and intervened in the diagnostic and therapeutical plan of patients, participating in clinical decisions and coordinating patient navigation with neurosurgeons. The incidence of moderate or severe complications measured by the Accordion Severity Grading System, in-hospital mortality, and length of stay of the two cohorts were compared. Multivariate regression was used to adjust for confounders, and the average treatment effect was estimated using inverse probability of treatment weighting. RESULTS: The adjusted incidence of moderate or severe complications was lower among co-managed patients (odds ratio [OR] 0.60, 95% confidence interval [CI] 0.39-0.91). Mortality was unchanged (OR 0.83, 95% CI 0.15-4.17). Length of stay was lower in co-managed patients, with a 1.3-day reduction observed after inverse probability of treatment weighting analysis. CONCLUSION: Hospitalist co-management was associated with a reduced incidence of complications and length of stay in neurosurgical patients, but there was no difference in in-hospital mortality.

Predictive value of fecal calprotectin and lactoferrin levels for negative outcomes in Clostridioides difficile infection.

PURPOSE: We investigated the role of fecal calprotectin (FC) and lactoferrin (FL) as predictive biomarkers in Clostridioides difficile infection (CDI). METHODS: We assembled a prospective cohort including all patients with a laboratory-confirmed CDI diagnosis between January and December 2017. FL and FC levels were measured at diagnosis by commercial ELISA and EIA kits. We investigated the diagnostic accuracy of FC and FL to predict CDI recurrence and severity (study outcomes) and explored optimal cut-off values in addition to those proposed by the manufacturers (200 µg/g and 7.2 µg/mL, respectively). RESULTS: We included 170 CDI cases (152 first episodes and 18 recurrences). The rates of recurrence (first episodes only) and severity (entire cohort) were 9.2% (14/152) and 46.5% (79/170). Both FL and FC levels were significantly higher in patients who developed study outcomes. Optimal cut-off values for FC and FL to predict CDI recurrence were 1052 µg/g and 6.0 µg/mL. The optimal cut-off value for FC yielded higher specificity (60.9%) and positive predictive value (PPV) (16.9%) than that proposed by the manufacturer. Regarding CDI severity, the optimal cut-off value for FC (439 µg/g) also provided higher specificity (43.9%) and PPV (54.1%) than that of the manufacturer, whereas the optimal cut-off value for FL (4.6 µg/mL) resulted in an improvement of PPV (57.5%). CONCLUSION: By modifying the thresholds for assay positivity, the measurement of FC and FL at diagnosis is useful to predict recurrence and severity in CDI. Adding these biomarkers to current clinical scores may help to individualize CDI management.

Lack of interactions between prenatal immune activation and Δ9-tetrahydrocannabinol exposure during adolescence in behaviours relevant to symptom dimensions of schizophrenia in rats.

The causality in the association between cannabis use and the risk of developing schizophrenia has been the subject of intense debate in the last few years. The development of animal models recapitulating several aspects of the disease is crucial for shedding light on this issue. Given that maternal infections are a known risk for schizophrenia, here, we used the maternal immune activation (MIA) model combined with THC exposure during adolescence to examine several behaviours in rats (working memory in the Y maze, sociability in the three-chamber test, sucrose preference as a measure, prepulse inhibition and formation of incidental associations) that are similar to the different symptom clusters of the disease. To this end, we administered LPS to pregnant dams and when the offspring reached adolescence, we exposed them to a mild dose of THC to examine their behaviour in adulthood. We also studied several parameters in the dams, including locomotor activity in the open field, elevated plus maze performance and their response to LPS, that could predict symptom severity of the offspring, but found no evidence of any predictive value of these variables. In the adult offspring, MIA was associated with impaired working memory and sensorimotor gating, but surprisingly, it increased sociability, social novelty and sucrose preference. THC, on its own, impaired sociability and social memory, but there were no interactions between MIA and THC exposure. These results suggest that, in this model, THC during adolescence does not trigger or aggravate symptoms related to schizophrenia in rats.

Prefrontal circuits encode both general danger and specific threat representations.

Behavioral adaptation to potential threats requires both a global representation of danger to prepare the organism to react in a timely manner but also the identification of specific threatening situations to select the appropriate behavioral responses. The prefrontal cortex is known to control threat-related behaviors, yet it is unknown whether it encodes global defensive states and/or the identity of specific threatening encounters. Using a new behavioral paradigm that exposes mice to different threatening situations, we show that the dorsomedial prefrontal cortex (dmPFC) encodes a general representation of danger while simultaneously encoding a specific neuronal representation of each threat. Importantly, the global representation of danger persisted in error trials that instead lacked specific threat identity representations. Consistently, optogenetic prefrontal inhibition impaired overall behavioral performance and discrimination of different threatening situations without any bias toward active or passive behaviors. Together, these data indicate that the prefrontal cortex encodes both a global representation of danger and specific representations of threat identity to control the selection of defensive behaviors.

Reconstruction technique of multiligamentous knee injury in a patient with traumatic transtibial amputation.

Multiligamentary knee injuries associated with transtibial amputation is a pathologie with a low incidence, so their diagnosis and treatment represent a great challenge for the medical team, mainly due to the low rate of scientific publications on the matter. This article intends to present the treatment of a really infrequent pathology, presenting the clinical case of a polytraumatized patient who suffered a left transtibial amputation associated with a multiligament knee injury with dislocation of the proximal tibiofibular joint. After analyzing the multiple therapeutic options, a specific surgical planning is carried out for the specific case of a multiligament knee injury associated with an ipsilateral transtibial amputation, proceeding to the execution of the reconstruction of the injury with good results. For this, several specific surgical gestures are carried out, adapted to the patient's condition, which will facilitate the surgery and are explained in the surgical technique. In conclusion, we must know that in order to obtain satisfactory results in these patients, it is important to carry out an early diagnosis and treatment of the injury, analyzing the proximal tibiofibular stability and providing adequate stability through the execution of a precise surgical technique.

Recurrent Pediatric Extranasopharyngeal Angiofibroma of the Epiglottis: Case Report.

Angiofibroma is a non-encapsulated, highly vascular tumor that usually originates in the nasopharynx. Laryngeal cases of extranasopharyngeal angiofibroma (ENA) are a very rare pathology, especially in children. Only eight ENA laryngeal cases have been described in the literature, and only one of them is a pediatric case. In this report we present an 11-year-old child with epiglottic ENA resected with transoral endoscopic ultrasonic surgery (TOUSS) with review of the literature. Because of reccurrence after five months he underwent re-excision with CO2 laser. Recurrences in ENA are infrequent, but as demonstrated in our case, close endoscopic follow-up is mandatory in this location. Endoscopic hemostatic procedures like TOUSS and CO2 laser ensure bloodless surgery for the management of this type of vascular laryngeal tumors.

CK1δ and CK1ε Signaling Sustains Mitochondrial Metabolism and Cell Survival in Multiple Myeloma.

Multiple myeloma remains an incurable malignancy due to acquisition of intrinsic programs that drive therapy resistance. Here we report that casein kinase-1δ (CK1δ) and CK1ε are therapeutic targets in multiple myeloma that are necessary to sustain mitochondrial metabolism. Specifically, the dual CK1δ/CK1ε inhibitor SR-3029 had potent in vivo and ex vivo anti-multiple myeloma activity, including against primary multiple myeloma patient specimens. RNA sequencing (RNA-seq) and metabolic analyses revealed inhibiting CK1δ/CK1ε disables multiple myeloma metabolism by suppressing genes involved in oxidative phosphorylation (OxPhos), reducing citric acid cycle intermediates, and suppressing complexes I and IV of the electron transport chain. Finally, sensitivity of multiple myeloma patient specimens to SR-3029 correlated with elevated expression of mitochondrial genes, and RNA-seq from 687 multiple myeloma patient samples revealed that increased CSNK1D, CSNK1E, and OxPhos genes correlate with disease progression and inferior outcomes. Thus, increases in mitochondrial metabolism are a hallmark of multiple myeloma progression that can be disabled by targeting CK1δ/CK1ε. SIGNIFICANCE: CK1δ and CK1ε are attractive therapeutic targets in multiple myeloma whose expression increases with disease progression and connote poor outcomes, and that are necessary to sustain expression of genes directing OxPhos.

Cooperative Synthesis of Raspberry-Like Covalent Organic Framework-Polymer Particles with a Radial Single-Crystal Grain Orientation.

Despite many efforts devoted toward the design of covalent organic frameworks (COFs) at the framework level by selecting the building blocks, their organization in the nano to meso regimes is often neglected. Moreover, the importance of processability for their applications has recently emerged and the synthesis of COF nanostructures without agglomeration is still a challenge. Herein, the first example of hybrid COF-polymer particles for which polymers are used to manipulate the 2D COF growth along a specific direction is reported. The study examines how the nature, chain-end functionality, and molar mass of the polymer influence the shaping of hybrid 2D boronate ester-linked COF-polymer particles. Catechol-poly(N-butyl acrylate) leads to the self-assembly of crystallites into quasi-spherical structures while catechol-poly(N-isopropylacrylamide) mediates the synthesis of raspberry-like COF-polymer particles with radial grain orientation. Scanning and transmission electron microscopies (SEM and TEM) and 4D-STEM-ACOM (automated crystal orientation mapping) highlight the single-crystal character of these domains with one plane family throughout the particles. Interestingly, the presence of PNIPAm on the particle surface allows their drying without co-crystallization and enables their resuspension. Kinetic investigations show that catechol-PnBuA acts as a modulator and catechol-PNIPAm induces a template effect, introducing supramolecular self-assembly properties into particles to create new morphologies with higher structural complexity, beyond the framework level.

Modulating the polyamine/hypusine axis controls generation of CD8+ tissue-resident memory T cells.

Glutaminolysis is a hallmark of the activation and metabolic reprogramming of T cells. Isotopic tracer analyses of antigen-activated effector CD8+ T cells revealed that glutamine is the principal carbon source for the biosynthesis of polyamines putrescine, spermidine, and spermine. These metabolites play critical roles in activation-induced T cell proliferation, as well as for the production of hypusine, which is derived from spermidine and is covalently linked to the translation elongation factor eukaryotic translation initiation factor 5A (eIF5A). Here, we demonstrated that the glutamine/polyamine/hypusine axis controlled the expression of CD69, an important regulator of tissue-resident memory T cells (Trm). Inhibition of this circuit augmented the development of Trm cells ex vivo and in vivo in the BM, a well-established niche for Trm cells. Furthermore, blocking the polyamine/hypusine axis augmented CD69 expression as well as IFN-γ and TNF-α production in (a) human CD8+ T cells from peripheral blood and sarcoma tumor infiltrating lymphocytes and (b) human CD8+ CAR-T cells. Collectively, these findings support the notion that the polyamine-hypusine circuit can be exploited to modulate Trm cells for therapeutic benefit.

Could machine learning algorithms help us predict massive bleeding at prehospital level?

OBJECTIVE: Comparison of the predictive ability of various machine learning algorithms (MLA) versus traditional prediction scales (TPS) for massive hemorrhage (MH) in patients with severe traumatic injury (STI). DESIGN: On a database of a retrospective cohort with prehospital clinical variables and MH outcome, a treatment of the database was performed to be able to apply the different AML, obtaining a total set of 473 patients (80% training, 20% validation). For modeling, proportional imputation and cross validation were performed. The predictive power was evaluated with the ROC metric and the importance of the variables using the Shapley values. SETTING: Out-of-hospital care of patients with STI. PARTICIPANTS: Patients with STI treated out-of-hospital by a out-of-hospital medical service from January 2010 to December 2015 and transferred to a trauma center in Madrid. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: Obtaining and comparing the "Receiver Operating Characteristic curve" (ROC curve) metric of four MLAs: "random forest" (RF), "vector support machine" (SVM), "gradient boosting machine" (GBM) and "neural network" (NN) with the results obtained with TPS. RESULTS: The different AML reached ROC values higher than 0.85, having medians close to 0.98. We found no significant differences between AMLs. Each AML offers a different set of more important variables with a predominance of hemodynamic, resuscitation variables and neurological impairment. CONCLUSIONS: MLA may be helpful in patients with HM by outperforming TPS.