Unveiling the Mechanism of Phonon-Polariton Damping in α-MoO3.

Phonon polaritons (PhPs), light coupled to lattice vibrations, in the highly anisotropic polar layered material molybdenum trioxide (α-MoO3) are currently the focus of intense research efforts due to their extreme subwavelength field confinement, directional propagation, and unprecedented low losses. Nevertheless, prior research has primarily concentrated on exploiting the squeezing and steering capabilities of α-MoO3 PhPs, without inquiring much into the dominant microscopic mechanism that determines their long lifetimes, which is key for their implementation in nanophotonic applications. This study delves into the fundamental processes that govern PhP damping in α-MoO3 by combining ab initio calculations with scattering-type scanning near-field optical microscopy (s-SNOM) and Fourier transform infrared (FTIR) spectroscopy measurements across a broad temperature range (8-300 K). The remarkable agreement between our theoretical predictions and experimental observations allows us to identify third-order anharmonic phonon-phonon scattering as the main damping mechanism of α-MoO3 PhPs. These findings shed light on the fundamental limits of low-loss PhPs, which is a crucial factor for assessing their implementation into nanophotonic devices.

First consensus document of waiting list prioritization for liver transplantation by the Spanish Society of Liver Transplantation (SETH).

Spain is worldwide leader in deceased donation rates per million habitants and count on a strong network of twenty-five liver transplant institutions. Although the access to liver transplantation is higher than in other countries, approximately 10% of patients qualifying for liver transplantation in Spain will die in the waiting list or would be excluded due to clinical deterioration. A robust waiting list prioritization system is paramount to grant the sickest patients with the first positions in the waiting list for an earlier access to transplant. In addition, the allocation policy may not create or perpetuate inequities, particularly in a public and universal healthcare system. Hitherto, Spain lacks a unique national allocation system for elective liver transplantation. Most institutions establish their own rules for liver allocation and only two autonomous regions, namely Andalucía and Cataluña, share part of their waiting list within their territory to provide regional priority to patients requiring more urgent transplantation. This heterogeneity is further aggravated by the recently described sex-based disparities for accessing liver transplantation in Spain, and by the expansion of liver transplant indications, mainly for oncological indications, in absence of clear guidance on the optimal prioritization policy. The present document contains the recommendations from the first consensus of waiting list prioritization for liver transplantation issued by the Spanish Society of Liver Transplantation (SETH). The document was supported by all liver transplant institutions in Spain and by the Organización Nacional de Trasplantes (ONT). Its implementation will allow to homogenize practices and to improve equity and outcomes among patients with end-stage liver disease.

Predictive and dynamic signature for anti-angiogenics in combination with PD-1 inhibitor in soft-tissue sarcoma: correlative studies linked to the IMMUNOSARC trial.

PURPOSE: IMMUNOSARC trial combined an anti-angiogenic agent (sunitinib) with a PD-1 inhibitor (nivolumab) in advanced sarcomas. Here we present the first correlative studies of the STS cohort enrolled in this trial. EXPERIMENTAL DESIGN: Formalin-fixed paraffin-embedded (FFPE) and peripheral blood samples were collected at baseline and week 13. FFPE were used for transcriptomics and multiplex immunofluorescence, while peripheral blood samples were used for multiplexed immunoassays. Flow cytometry and Luminex assays were performed to validate translational findings in tumor-isolated cells and peripheral blood mononuclear cells derived from patients. RESULTS: The density of intratumoral CD8+ T cells, measured by multiplexed immuno-phenotyping, was significantly increased after treatment. This augment was accompanied by the dynamic significant increase in gene expression of CD86, CHI3L1, CXCL10, CXCL9, LAG3, and VCAM1, and the decrease in the expression levels of NR4A1. In peripheral blood, 12 proteins were significantly modulated by treatment at W13. A score integrating the dynamic expression of the 7 genes and the 12 soluble factors separated two groups with distinct progression-free survival (PFS): 4.1 months (95% CI 3.5-NR) vs 17 months (95% CI 12.0 - NR), p=0.014. This molecular score was predictive of PFS when applied to the normalized data determined in the baseline samples. CONCLUSIONS: Treatment with sunitinib and nivolumab inflamed the sarcoma microenvironment, increasing CD8+ T cell density and the expression of several genes/ proteins with relevance in the response to PD-1 inhibitors. A molecular signature identified two groups of patients with distinct PFS for the combination of anti-angiogenics plus PD-1 inhibitor.

Identification of predictive models including polymorphisms in cytokines genes and clinical variables associated with post-transplant complications after identical HLA-allogeneic stem cell transplantation.

Backgrounds: Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative therapy for hematological malignancies, it can be associated with relevant post-transplant complications. Several reports have shown that polymorphisms in immune system genes are correlated with the development of post-transplant complications. Within this context, this work focuses on identifying novel polymorphisms in cytokine genes and developing predictive models to anticipate the risk of developing graft-versus-host disease (GVHD), transplantation-related mortality (TRM), relapse and overall survival (OS). Methods: Our group developed a 132-cytokine gene panel which was tested in 90 patients who underwent an HLA-identical sibling-donor allo-HSCT. Bayesian logistic regression (BLR) models were used to select the most relevant variables. Based on the cut-off points selected for each model, patients were classified as being at high or low-risk for each of the post-transplant complications (aGVHD II-IV, aGVHD III-IV, cGVHD, mod-sev cGVHD, TRM, relapse and OS). Results: A total of 737 polymorphisms were selected from the custom panel genes. Of these, 41 polymorphisms were included in the predictive models in 30 cytokine genes were selected (17 interleukins and 13 chemokines). Of these polymorphisms, 5 (12.2%) were located in coding regions, and 36 (87.8%) in non-coding regions. All models had a statistical significance of p<0.0001. Conclusion: Overall, genomic polymorphisms in cytokine genes make it possible to anticipate the development all complications studied following allo-HSCT and, consequently, to optimize the clinical management of patients.

Mounting an immune response reduces male attractiveness in a lizard.

Parasites impact host fitness and constitute an important selective pressure on the host's life history. According to parasite-mediated sexual selection, ornaments are presumed to honestly indicate immune capacity or resistance against parasites, and the chooser sex (typically females) obtains an advantage by selecting more ornamented, thus more immunocompetent mates. Therefore, signalers mounting an immune response must allocate resources from the sexual signal to the immune system, hence reducing the expression of the ornament and becoming less attractive to the choosing sex. Here, we test this idea in the lizard Psammodromus algirus. We inoculated a subsample of males with lipopolysaccharide (LPS) of the cell wall of Escherichia coli, while others served as sham controls. The inoculation of LPS decreased the proportion of ergosterol (pro-vitamin D2) in femoral secretions, and chemosensory tests showed that the scent of LPS-inoculated males was less attractive to females than the scent of control males. Given that ergosterol is a precursor of vitamin D, which has physiological functions as an immune modulator, immunocompromised males likely needed to divert vitamin D to the immune system, reducing the allocation of ergosterol to secretions. In this way, females could detect "sick" males, preferring the apparently healthy males. Overall, our study shows that mounting an immune response is costly in terms of reduced attractiveness. Moreover, we disentangle the underlying mechanism, which involves an honest signal based on vitamin D allocation.

Osseointegrated dental implants that will undergo radiotherapy. Does risk of osteoradionecrosis exist? A scoping review.

OBJECTIVE: Given the absence of a standardized action protocol for treating patients with dental implants (DIs) who are subjected to radiotherapy (RT), we have conducted an extensive review and analysis of published literature on this subject. Our objective is to gain a comprehensive understanding of the impact of RT on the bone surrounding osseointegrated implants during and after treatment. STUDY DESIGN: We conducted a literature review using PubMed (MEDLINE) to identify studies describing the effects of RT on preexisting osseointegrated and/or loaded DIs. Articles published between January 1963 and December 2023 were considered for inclusion. RESULTS: A total of 1,126 articles were retrieved, 64 full articles were reviewed, and only 13 articles were included in this review upon meeting the criteria. A total of 667 patients and 2,409 implants were included. Osteoradionecrosis (ORN) was observed in approximately 19 implants following antineoplastic treatment. CONCLUSIONS: The interaction between DIs and RT is a complex and multifaceted issue that requires further research and clinical guidance. Although certain studies indicate a possible connection between DIs, radiation, and ORN risk, the precise relationship remains unclear. Factors such as radiation dosage, implant characteristics, material, and timing of placement significantly influence this association.

A phase III randomized controlled trial of plitidepsin, a marine derived compound, in hospitalized adults with moderate COVID-19.

BACKGROUND: Plitidepsin has shown potent preclinical activity against SARS-CoV-2 and was generally well tolerated in a Phase I trial of hospitalized patients with COVID-19. NEPTUNO, a Phase III, multicenter, randomized, controlled trial, was designed to evaluate the efficacy and safety of plitidepsin in the management of moderate COVID-19 in hospitalized adult patients. METHODS: Included patients had documented SARS-CoV-2 infection, required oxygen therapy, and had adequate organ function. The planned sample size was 609 patients. Patients were randomized 1:1:1 to at least 3 days of dexamethasone plus either plitidepsin (1.5 mg/day or 2.5 mg/day, for 3 days) or standard of care (control). The primary endpoint was the time to sustained withdrawal of supplemental oxygen. Secondary endpoints included time to sustained hospital discharge, clinical status, duration of oxygen support, percentage of patients requiring admission to the intensive care unit, and safety. FINDINGS: After randomizing 205 patients, NEPTUNO was discontinued due to a notable drop in COVID-19-related hospitalizations. Available data suggest a 2-day improvement in the median time to sustained oxygen therapy discontinuation (5 vs 7 days) favoring both plitidepsin arms (hazard ratio [HR] 1.37, 95% confidence interval [CI] 0.96-1.96, p=0.08 for plitidepsin 1.5 mg vs control; HR 1.06, 95% CI 0.73-1.53, p=0.78 for plitidepsin 2.5 mg vs control). Plitidepsin was generally well tolerated. INTERPRETATION: Despite the trial limitations, these results suggest that plitidepsin may have a positive benefit-risk ratio in the management of patients requiring oxygen therapy. Further studies with plitidepsin, including those in immunosuppressed patients, are warranted. FUNDING: This trial has been funded by Pharmamar, S.A. (Madrid, Spain).

Histological and immunohistochemical soft-tissue response to cylindrical and concave abutments: Multicenter randomized clinical trial.

BACKGROUND: This study aimed to analyze the influence of concave and cylindrical abutments on peri-implant soft tissue. Dimensions, collagen fiber orientation, and immunohistochemical data were assessed. METHODS: A multicenter, split-mouth, double-blind randomized clinical trial was conducted. Two groups were analyzed: cylindrical abutments and concave abutments. After a 12-week healing period, peri-implant soft tissue samples were collected, processed, and evaluated for dimensions, collagen fiber orientation, and immunohistochemical data. Inflammatory infiltration and vascularization were assessed, and the abutment surfaces were analyzed using scanning electron microscopy. The statistical analysis was performed using the SPSS version 20.0 statistical package. RESULTS: A total of 74 samples in 37 patients were evaluated. Histological evaluation of peri-implant soft tissue dimensions revealed significant differences between concave and cylindrical abutments. Concave abutments exhibited greater total height (concave: 3.57 ± 0.28 - cylindrical: 2.95 ± 0.27) and barrier epithelium extension (concave: 2.46 ± 0.17 - cylindrical: 1.89 ± 0.21) (p < 0.05), while the supracrestal connective tissue extension (concave: 1.11 ± 0.17 - cylindrical: 1.03 ± 0.16) was slightly greater (p > 0.05). Collagen fiber orientation favored concave abutments (23.76 ± 5.86), with significantly more transverse/perpendicular fibers than for cylindrical abutments (15.68 ± 4.57). The immunohistochemical analysis evidenced greater inflammatory and vascular intensity in the lower portion for both abutments, though concave abutments showed lower overall intensity (concave: 1.05 ± 0.78 - cylindrical: 1.97 ± 0.68) (p < 0.05). The abutment surface analysis demonstrated a higher percentage of tissue remnants on concave abutments (42.47 ± 1.32; 45.12 ± 3.03) (p < 0.05). CONCLUSIONS: Within the limitations of this study, concave abutments presented significantly greater peri-implant tissue height, linked to an extended barrier epithelium, versus cylindrical abutments in thick tissue phenotype. This enhanced soft tissue sealing, favoring a greater percentage of transversely oriented collagen fibers. The concave design reduced chronic inflammatory exudation with T and B cells, thus minimizing the risk of chronic inflammation. PLAIN LANGUAGE SUMMARY: This study looked at how 2 different shapes of dental implant abutments (the parts that connect the implant to the crown), specifically concave and cylindrical, affect the soft tissue around the implants. We wanted to see how these shapes influenced the tissue's size, structure, and health. We conducted a clinical trial with 37 patients, comparing the 2 types of abutments in the same mouth over 12 weeks. Our findings showed that the concave abutments led to a taller and more extensive layer of protective tissue around the implant compared to the cylindrical ones. This protective tissue had more favorable collagen fiber orientation, which is important for the strength and health of the tissue. Additionally, the concave abutments resulted in less inflammation and better tissue integration. In conclusion, concave abutments may provide better support and health for the soft tissue around dental implants, reducing the risk of chronic inflammation and potentially leading to better long-term outcomes for patients with dental implants.

Time above range and no coefficient of variation is associated with diabetic retinopathy in individuals with type 1 diabetes and glycated hemoglobin within target.

AIMS: This study aimed to investigate the association between glucose metrics and diabetic retinopathy in type 1 diabetes (T1D) patients using flash continuous glucose monitoring (FGM) systems, including those maintaining glycated hemoglobin (HbA1c) within the target range. METHODS: We conducted a cross-sectional study involving 1070 T1D patients utilizing FGM systems. Data on clinical, anthropometric, and socioeconomic characteristics were collected and retinopathy was classified based on international standards. RESULTS: Patients' mean age was 47.6 ± 15.0 years, with 49.4% of them being females. Within the cohort, 24.8% of patients presented some form of retinopathy. In the analysis involving the entire sample of subjects, male gender (OR = 1.51, p = 0.027), Time Above Range (TAR) > 250 mg/dL (OR = 1.07, p = 0.025), duration of diabetes (OR = 1.09, p < 0.001), smoking (OR = 2.30, p < 0.001), and history of ischemic stroke (OR = 5.59, p = 0.025) were associated with diabetic retinopathy. No association was observed between the coefficient of variation and diabetic retinopathy (p = 0.934). In patients with HbA1c < 7%, the highest quartile of TAR > 250 was independently linked to diabetic retinopathy (OR = 8.32, p = 0.040), in addition to smoking (OR = 2.90, p = 0.031), duration of diabetes (OR = 1.09, p < 0.001), and hypertension (OR = 2.35, p = 0.040). CONCLUSION: TAR > 250 mg/dL significantly emerges as a modifiable factor associated with diabetic retinopathy, even among those patients maintaining recommended HbA1c levels. Understanding glucose metrics is crucial for tailoring treatment strategies for T1D patients.

Intracardiac vascular access in haemodialysis: A last resort for exhausted traditional access.

Depletion of veins for dialysis access is a challenging life threatening situation for patients in need of haemodialysis. The utilisation of intracardiac catheter is a rare procedure with scarce reported experience. We describe the case of a 68-year-old male that contributes to the limited knowledge of performing a life-saving intracardiac catheter placement for emergency haemodialysis in a patient without immediate alternative renal replacement therapy available. We also retrospectively analyse the experience reported so far and summarise complications and outcomes. In our case, the patient was able to pursue haemodialysis after intracardiac catheter placement without any complications. Two weeks later, the patient successfully received a kidney transplant from a deceased donor and has a serum creatinine of 1.7 mg/dL after 2 years of follow-up. There are only four reported cases of kidney transplantation after the procedure, including our own. Intracardiac catheter is an emerging option that could be considered in certain patients as the last resort. Further investigation with regards to patient candidacy and procedure security are necessary.

C-Peptide and BMi predict anti-hyperglycemic treatment lines in breast cancer patients treated with Alpelisib.

PURPOSE: Alpelisib is a PI3K (Phosphoinositide 3-kinases) inhibitor used for breast cancer which develops hyperglycemia based on its action on glucose metabolism regulation. This study aims to identify potential risk factors predicting hyperglycemia development and the need for multiple treatments for hyperglycemia in patients receiving Alpelisib. METHODS: Fourteen women diagnosed with metastatic hormone receptor-positive breast cancer carrying PI3K mutations who initiated treatment with Alpelisib were monitored through consultations in the Oncology and Endocrinology departments. Non-parametric ROC curves were generated to assess the need for three or more antidiabetic medications to achieve glycemic control. RESULTS: The study population had a median age of 64 years (range:48-69) with a median body mass index (BMI) of 26.6 kg/m2 (range: 22.9-29.4). Overweight was observed in 35.7% of the participants and obesity in 21.4%. Fifty percent of the participants had prediabetes, and 85.7% developed hyperglycemia requiring pharmacological treatment, although none of them needed to discontinue treatment for this reason. Baseline C-peptide levels and BMI were associated with the number of antidiabetic drugs used (Spearman's Rho 0.553, p = 0.040; Spearman's Rho 0.581, p = 0.030, respectively). ROC curve analysis showed and area under the curve (AUC) of 0.819 for the variable risk profile (defined as baseline C-peptide >10.5 ng/ml and BMI > 27 kg/m2), whereas AUC values were 0.556 and 0.514 for HbA1c and baseline glucose, respectively, (p = 0.012). CONCLUSION: A joint follow-up by an Oncology department and a Diabetes Unit can prevent treatment discontinuation in patients under Alpelisib therapy. Baseline BMI and plasma C-peptide levels can predict an increased need for anti-hyperglycemic treatment.

Do sexual differences in life strategies make male lizards more susceptible to parasite infection?

Female and male hosts may maximise their fitness by evolving different strategies to compensate for the costs of parasite infections. The resulting sexual dimorphism might be apparent in differential relationships between parasite load and body condition, potentially reflecting differences in energy allocation to anti-parasitic defences. For example, male lacertids with high body condition may produce many offspring while being intensely parasitised. In contrast, female lacertids may show a different outcome of the trade-offs between body condition and immunity, aiming to better protect themselves from the harm of parasites. We predicted that females would have fewer parasites than males and a lower body condition across parasitaemia levels because they would invest resources in parasite defence to mitigate the costs of infection. In contrast, the male strategy to maximise access to females would imply some level of parasite tolerance and, thus, higher parasitaemia. We analysed the relationship between the body condition of lizards and the parasitemias of Karyolysus and Schellackia, two genera of blood parasites with different phylogenetic origins, in 565 females and 899 males belonging to 10 species of the Lacertidae (Squamata). These lizards were sampled over a period of 12 years across 34 sampling sites in southwestern Europe. The results concerning the Karyolysus infections were consistent with the predictions, with males having similar body condition across parasitaemia levels even though they had higher infection intensities than females. On the other hand, females with higher levels of Karyolysus parasitaemia had lower body condition. This is consistent with the prediction that different life strategies of male and female lacertids can explain the infection patterns of Karyolysus. In contrast, the parasitaemia of Schellackia was consistently low in both male and female hosts, with no significant effect on the body condition of lizards. This suggests that lizards of both sexes maintain this parasite below a pathogenic threshold.

Los machos y hembras pueden maximizar su eficacia biológica mediante la evolución diferencial de estrategias que compensen los costes asociados con las infecciones parasitarias. Por ejemplo, los machos con una alta condición corporal pueden producir muchas crías aun estando altamente parasitados. Mientras que es común que las hembras inviertan más energía en protegerse frente a los parásitos, lo que podría comprometer el mantenimiento de su condición corporal. Nuestra hipótesis es que las diferencias sexuales en la asignación de energía pueden quedar de manifiesto al analizar la relación entre la intensidad de infección con la condición corporal. También esperamos que las hembras tengan menos parásitos que los machos y que su condición corporal esté correlacionada negativamente con su carga parasitaria. Por el contrario, esperamos que los machos tengan más parásitos en parte porque su estrategia implicaría cierto nivel de tolerancia si con ello pueden incrementar su inversión reproductiva. Hemos analizado la relación entre la condición corporal y las parasitemias de Schellackia y Karyolysus, dos parásitos sanguíneos, en 565 hembras y 899 machos de 10 especies de la familia Lacertidae (Squamata) durante 12 años en 34 localidades en el suroeste de Europa. El patrón para Karyolysus fue coherente con las predicciones, ya que la condición corporal de los machos no se correlacionó con su parasitemia, a pesar de que estas fueron mayores que en las hembras. Mientras que la relación fue negativa en las hembras. Por lo que el patrón de infección de Karyolysus concuerda con las diferentes estrategias de inversión energética en machos y hembras. Sin embargo, en el caso de Schellackia las parasitemias fueron más bajas en hospedadores de ambos sexos y su parasitemia no se correlacionó con la condición corporal. Este resultado sugiere que Schellackia es mantenido en umbrales subpatogénicos.

Pre-operative thyroglobulin measurement for thyroid cancer risk of recurrence and response to therapy.

BACKGROUND: Thyroid cancer has an overall favorable prognosis, but no pre-operative biochemical marker has been shown to distinguish between low and high-risk disease or predict response to therapy. METHODS: We retrospectively reviewed 162 patients that underwent thyroid surgery for thyroid cancer between 2006 and 2022 in whom a pre-operative thyroglobulin level (Tg) was measured. We subdivided patients into low, intermediate and high-risk thyroid cancer and based on their response to therapy per ATA guidelines. RESULTS: We showed that as pre-operative Tg level increased, patients were more likely to have high-risk disease (p â€‹< â€‹0.01). We found a linear association between the primary tumor size and high-risk histology with pre-operative Tg (p â€‹< â€‹0.01). Pre-operative Tg level was significantly associated with response to therapy following initial surgical management. Specifically, as pre-operative Tg increases, patients were less likely to achieve an excellent response (p â€‹< â€‹0.01). CONCLUSIONS: Our retrospective analysis demonstrated that pre-operative Tg is significantly associated with ATA structural risk of recurrence and response to therapy and may have the potential to guide initial therapy and follow-up management.

Social determinants of health influencing the choice of dialysis modality in advanced chronic kidney disease: Need of an interdisciplinary approach.

INTRODUCTION: The influence of socioeconomic and cultural barriers in the choice of renal replacement therapy (RRT) techniques in advanced chronic kidney disease (ACKD) has been scarcely explored, which can generate problems of inequity, frequently unnoticed in health care. The aim of this study is to identify the "non-medical" barriers that influence the choice of RRT in an advanced chronic kidney disease (ACKD) consultation in Spain. MATERIAL AND METHODS: Retrospective analysis including the total number of patients seen in the ACKD consultation in a tertiary hospital from 2009 to 2020. Inclusion in the ACKD consultation began with an eligibility test and a decision-making process, conducted by a specifically trained nurse. The variables considered for the study were: age, sex, etiology of CKD, level of dependence for basic activities of daily living (Barthel Scale) and instrumental activities of daily living (Lawton and Brody Scale), Spanish versus foreign nationality, socioeconomic level and language barrier. The socioeconomic level was extrapolated according to home and health district by primary care center to which the patients belonged. RESULTS: A total of 673 persons were seen in the ACKD consultation during the study period, of whom 400 (59.4%) opted for hemodialysis (HD), 156 (23.1%) for peritoneal dialysis (PD), 4 (0.5%) for early living donor renal transplantation (LDRT) and 113 (16.7%) chose conservative care (CC). The choice of PD as the chosen RRT technique (vs. HD) was associated with people with a high socioeconomic level (38.7% vs. 22.5%) (p = 0.002), Spanish nationality (91% vs. 77.7%) (p < 0.001), to a lower language barrier (0.6% vs 10.5%) (p < 0.001), and to a higher score on the Barthel scale (97.4 vs 92.9) and on the Lawton and Brody scale (7 vs 6.1) (p < 0.001). Neither age nor sex showed significant differences in the choice of both techniques. Patients who opted for CC were significantly older (81.1 vs 67.7 years; p < 0.001), more dependent (p < 0.001), with a higher proportion of women (49.6% vs 35.2%; p = 0.006) and a higher proportion of Spaniards (94.7% vs 81%, p = 0.001) in relation to the choice of other techniques (PD and HD). Socioeconomic level did not influence the choice of CC. CONCLUSION: Despite a regulated decision-making process, there are factors such as socioeconomic status, migration, language barrier and dependency of the population that influence the type of RRT chosen. To address these aspects that may cause inequity, an intersectoral and multilevel intervention is required with interdisciplinary teams that include, among others, social workers, to provide a more holistic and person-centered assessment.

Analyzing diagnostic and treatment wait times for lung cancer Patients: Key insights from a provincial registry study.

BACKGROUND: Lung cancer (LC) remains the leading cause of cancer-related mortality globally, necessitating timely diagnosis and treatment to improve patient outcomes. This study aimed to evaluate the timeliness of care for LC patients at a public hospital in Almería, Spain, assess adherence to guidelines, and explore associations between timeliness and survival. METHODS: A retrospective cohort study was conducted, reviewing medical records of LC patients diagnosed between 2019 and 2021. Quality indicators, adapted from prevailing guidelines, facilitated the assessment of care timeliness, with a focus on diagnostic and treatment wait times. Cox regression modeling was employed to explore survival associations, adjusting for covariates including age, performance status, stage, histology, and treatment modalities. RESULTS: Of 539 patients included, most (79.84 %) had initial specialist contact within 7 days, and 82.25 % received diagnosis within 30 days. However, delays were observed in treatment initiation, with surgery experiencing the longest median wait time (78 days). Survival analysis showed no significant difference between shorter and longer diagnostic (HR: 0.87, 95 % CI: 0.62-1.24) or treatment intervals (HR: 1.14, 95 % CI: 0.83-1.58). Multivariate analysis identified age, performance status, stage, histology, and treatment as prognostic factors. CONCLUSION: This study highlights the importance of timely diagnosis and treatment in improving lung cancer outcomes. Despite achieving diagnostic targets, treatment delays were common, particularly for surgical interventions. These findings underscore the need for enhanced coordination and efficient care pathways to minimize delays, ultimately improving survival rates and quality of life for lung cancer patients. Addressing these issues is crucial for optimizing lung cancer care delivery in the future.

Sleep and circadian rhythm alterations in myalgic encephalomyelitis/chronic fatigue syndrome and post-COVID fatigue syndrome and its association with cardiovascular risk factors: A prospective cohort study.

This study aimed to investigate circadian rhythm manifestations in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) patients (including a subpopulation of long-COVID patients) and matched healthy controls while also exploring their association with cardiovascular health variables. Thirty-one ME/CFS patients (75% females), 23 individuals diagnosed with post-COVID ME/CFS (56% females) and 31 matched healthy controls (68% females) were enrolled in this study. Demographic and clinical characteristics were assessed using validated self-reported outcome measures. Actigraphy data, collected over one week, were used to analyze the 24-h profiles of wrist temperature, motor activity, and sleep circadian variables in the study participants. Associations between lipid profile with endothelial dysfunction biomarkers (such as endothelin-1, ICAM-1 and VCAM-1) and with sleep and circadian variables were also studied. No differences were found in these variables between the two group of patients. Patients showed lower activity and worse sleep quality than matched healthy controls, together with a worse lipid profile than controls, that was associated with disturbances in the circadian temperature rhythm. ICAM-1 levels were associated with plasma lipids in healthy controls, but not in patients, who showed higher levels of endothelin-1 and VCAM-1. These findings suggest that lipid profiles in ME/CFS are linked to disrupted circadian rhythms and sleep patterns, likely due to endothelial dysfunction. Furthermore, they highlight the intricate relationship between sleep, circadian rhythms, and cardiovascular health in this condition.

Multidisciplinary Care for Moebius Syndrome and Related Disorders: Building a Management Protocol.

Moebius syndrome is a collection of orofacial anomalies with highly variable features affecting many different systems but characterised by bilateral facial palsy and absent eye abduction. We largely regard Moebius syndrome as a diagnosis of exclusion. Lack of awareness and knowledge means that children often fall between services, leading to treatment delays and difficulty interfacing with social care and schools, with long-term impact on physical health and psychosocial development. We developed a multidisciplinary team comprising core clinicians (lead physician, geneticist, speech and language therapist, psychologist and specialist nurse) and an expanded group to encompass the other affected systems. The interactions between our specialties lead to the development of a treatment protocol, which we present. The protocol harnesses the aspects of care of children with a range of other rare diseases at a specialised paediatric centre and synthesises them into a holistic approach for MBS and related conditions. Management is sequenced on an "ABC-style" basis, with airway, feeding, vision and speech taking priority in the early years. We define management priorities as airway stabilisation with swallow assessment, ocular surface protection and maintenance of nutritional support. Management principles for issues such as speech, reflux, drooling and sleep issues are outlined. In later years, psychological support has a prominent role geared towards monitoring and interventions for low mood, self-esteem and bullying.

Limited usefulness of the IS6110 touchdown-PCR in blood for tuberculin skin test false-negative cattle with serological response to Mycobacterium bovis.

Ante-mortem diagnosis of bovine tuberculosis (bTB) is based mainly on the tuberculin skin test (TST) and the ɣ-IFN release assay (IGRA). Some infected animals escape screening tests, thus, limit herd sanitation. Previous reports have suggested a predominant pattern of multi-organ lesions attributable to Mycobacterium bovis (the causative agent of bTB) bacteraemia. A case-control study was conducted to investigate blood PCR as an alternative tool for improving ante-mortem detection of TST false-negative bovines. Cases comprised 70 TST false-negative bovines (cases), which were serology positive, and controls included 81 TST positive bovines; all of them confirmed as infected with M. bovis. Detection of the IS6110 target through touchdown blood-PCR (IS6110 TD-PCR) was performed. The positivity of the blood-PCR was 27.2% in the control group. This performance was similar to the 15% obtained among cases (p = 0.134). Most cases identified by the IS6110 TD-PCR exhibited focalized lesions (p = 0.002). Results demonstrated that blood-PCR could detect TST false-negative cattle, even if they are negative for IGRA. Considering that cases exhibited humoral response to M. bovis, further studies conducted in a pre-serological stage could provide evidence about the real contribution of the technique in herds.