Electronic Coherences Excited by an Ultra Short Pulse Are Robust with Respect to Averaging over Randomly Oriented Molecules as Shown by Singular Value Decomposition.

We report a methodology for averaging quantum photoexcitation vibronic dynamics over the initial orientations of the molecules with respect to an ultrashort light pulse. We use singular value decomposition of the ensemble density matrix of the excited molecules, which allows the identification of the few dominant principal molecular orientations with respect to the polarization direction of the electric field. The principal orientations provide insights into the specific stereodynamics of the corresponding principal molecular vibronic states. The massive compaction of the vibronic density matrix of the ensemble of randomly oriented pumped molecules enables a most efficient fully quantum mechanical time propagation scheme. Two examples are discussed for the quantum dynamics of the LiH molecule in the manifolds of its electronically excited Σ and Π states. Our results show that electronic and vibrational coherences between excited states of the same symmetry are resilient to averaging over an ensemble of molecular orientations and can be selectively excited at the ensemble level by tuning the pulse parameters.

Bimekizumab: Short-Term Effectiveness and Safety in Real Clinical Practice in Andalucia, Spain.

Introduction: Psoriasis, a chronic inflammatory skin disease, affects 2-10% of the population globally. Bimekizumab (BMK), a monoclonal antibody targeting IL-17, is a dual inhibitor of IL17 A and F that has shown efficacy in treating moderate to severe plaque psoriasis. This real-world evidence (RWE) study aims to assess BMK's efficiency and safety in naïve and refractory patients. Material and methods: A retrospective analysis of a multicenter observational study included 22 patients treated with BMK from April 2023 to February 2023 in five Andalusian hospitals. Ethical approval was obtained, and patients provided informed consent. Assessment criteria encompassed Psoriasis Area and Severity Index (PASI), body surface area (BSA), VAS pruritus, Dermatology Life Quality Index (DLQI), and minimum disease activity (MDA) at 0, 4, 12, and 24 weeks. Results: Patients, predominantly with plaque psoriasis, exhibited significant improvements in PASI (baseline 15.7 to 0.4 at week 16), BSA (baseline 20.7 to 0.43 at week 16), DLQI (baseline 17.93 to 0.43 at week 16), and pruritus (baseline 7.12 to 0.4 at week 16). At week 16, 95.4% achieved MDA. No safety concerns or treatment discontinuations were reported. Discussion: This RWE study aligns with pivotal clinical trials, confirming BMK's efficacy and safety. Notably, BMK demonstrated rapid and sustained psoriasis clearance, even in challenging areas. The study's limitations include a small sample size, suggesting the need for further exploration of patient-reported outcomes. Conclusion: Bimekizumab exhibited optimal efficacy and safety profiles in treating moderate to severe plaque psoriasis in a real-world setting. Rapid response, sustained clearance, and favorable safety outcomes contribute to improved patient experiences. Future research could delve into patient-reported outcomes and expand sample sizes to enhance the understanding of BMK's real-world effectiveness.

Recombinant human soluble domain of CD39L3 and ticagrelor: cardioprotective effects in experimental myocardial infarction.

BACKGROUND AND AIMS: The ecto-nucleoside triphosphate diphosphohydrolases of the CD39 family degrade ATP and ADP into AMP, which is converted into adenosine by the extracellular CD73/ecto-5-nucleotidase. This pathway has been explored in antithrombotic treatments but little in myocardial protection. We have investigated whether the administration of solCD39L3 (AZD3366) confers additional cardioprotection to that of ticagrelor alone in a pre-clinical model of myocardial infarction (MI). METHODS: Ticagrelor-treated pigs underwent balloon-induced MI (90 min) and, before reperfusion, received intravenously either vehicle, 1 mg/kg AZD3366 or 3 mg/kg AZD3366. All animals received ticagrelor twice daily for 42 days. A non-treated MI group was run as a control. Serial cardiac magnetic resonance (baseline, Day 3 and Day 42 post-MI), light transmittance aggregometry, bleeding time, and histological and molecular analyses were performed. RESULTS: Ticagrelor reduced oedema formation and infarct size at Day 3 post-MI vs. controls. A 3 mg/kg AZD3366 provided an additional 45% reduction in oedema and infarct size compared with ticagrelor and a 70% reduction vs. controls (P < .05). At Day 42, infarct size declined in all ticagrelor-administered pigs, particularly in 3 mg/kg AZD3366-treated pigs (P < .05). Left ventricular ejection fraction was diminished at Day 3 in placebo pigs and worsened at Day 42, whereas it remained unaltered in ticagrelor ± AZD3366-administered animals. Pigs administered with 3 mg/kg AZD3366 displayed higher left ventricular ejection fraction upon dobutamine stress at Day 3 and minimal dysfunctional segmental contraction at Day 42 (χ2  P < .05 vs. all). Cardiac and systemic molecular readouts supported these benefits. Interestingly, AZD3366 abolished ADP-induced light transmittance aggregometry without affecting bleeding time. CONCLUSIONS: Infusion of AZD3366 on top of ticagrelor leads to enhanced cardioprotection compared with ticagrelor alone.

Role of Renal Venous Oxygen Pressure for Renal Function Monitoring After Related Living-Donor Kidney Transplantation: Cohort Study.

BACKGROUND: Monitoring of renal function after kidney transplantation (KT) is performed by measuring serum creatinine (SCr), urine volumes (UV), and glomerular filtration rate (GFR). Other methods based on oxygen metabolism, such as the renal venous oxygen pressure (PrvO2), may be useful. The aim of this study was to explore the correlation between PrvO2 and SCr, UV, and GFR 5 days after KT (SCr5, UV5, and GFR5, respectively). METHODS: We conducted a prospective cohort study in adults scheduled for living donor KT. A venous blood sample was taken from the renal vein after declamping the renal artery, and blood gas determinations were made. Correlation analyses between PrvO2 and SCr5, UV5, and GFR5 were done by calculating Spearman's correlation coefficient with generalized linear models (GLM). A Spearman's correlation analysis was performed between the percentage decrease in SCr (%ΔSCr) and PrvO2. A GLM was also performed to determine the association of PrvO2 with slow graft function (SGF). RESULTS: The study included 42 patients, of whom 67% were men. The median age was 31 years (IQR, 27-43.5). PrvO2 was negatively correlated with SCr5 (ρ = -0.53, P = .003), and positively correlated with GFR5 (ρ = 0.49, P = .001) and %ΔSCr (ρ = 0.47, P = .002). A higher PrvO2 was associated with an increase in GFR in univariable (ß = 1.24, 95% CI, 0.56-1.93, P = .001) and multivariable (ß = 1.24, 95% CI, 0.53-1.94, P = .001) analyses. No association was found between PrvO2 and SGF. CONCLUSION: PrvO2 could be used to monitor renal function in the first 5 days after related living-donor KT, given its good correlation with SCr and GFR.

Corpus callosum long-term biometry in very preterm children related to cognitive and motor outcomes.

BACKGROUND: The corpus callosum (CC) is suggested as an indirect biomarker of white matter volume, which is often affected in preterm birth. However, diagnosing mild white matter injury is challenging. METHODS: We studied 124 children born preterm (mean age: 8.4 ± 1.1 years), using MRI to assess CC measurements and cognitive/motor outcomes based on the Wechsler Intelligence Scale for Children-V (WPPSI-V) and Movement Assessment Battery for Children-2 (MABC-2). RESULTS: Children with normal outcomes exhibited greater height (10.2 ± 2.1 mm vs. 9.4 ± 2.3 mm; p = 0.01) and fractional anisotropy at splenium (895[680-1000] vs 860.5[342-1000]) and total CC length (69.1 ± 4.8 mm vs. 67.3 ± 5.1 mm; p = 0.02) compared to those with adverse outcomes. All measured CC areas were smaller in the adverse outcome group. Models incorporating posterior CC measurements demonstrated the highest specificity (83.3% Sp, AUC: 0.65) for predicting neurological outcomes. CC length and splenium height were the only linear measurements associated with manual dexterity and total MABC-2 score while both the latter and genu were related with Full-Scale Intelligence Quotient. CONCLUSIONS: CC biometry in children born very preterm at school-age is associated with outcomes and exhibits a specific subregion alteration pattern. The posterior CC may serve as an important neurodevelopmental biomarker in very preterm infants. IMPACT: The corpus callosum has the potential to serve as a reliable and easily measurable biomarker of white matter integrity in very preterm children. Estimating diffuse white matter injury in preterm infants using conventional MRI sequences is not always conclusive. The biometry of the posterior part of the corpus callosum is associated with cognitive and certain motor outcomes at school age in children born very preterm. Length and splenium measurements seem to serve as reliable biomarkers for assessing neurological outcomes in this population.

Natural history and prognostic factors of candidemia in kidney transplant recipients: A retrospective, multinational study.

BACKGROUND: The natural history of candidemia in kidney transplant recipients (KTR) remains poorly understood. This study aimed to evaluate mortality, prognostic factors and overall graft loss after candidemia in KTRs. METHODS: This is a retrospective multicentre study enrolling all KTRs ≥15 years old with candidemia diagnosed at hospitals in Brazil, Spain and Italy from 2010 to 2020. Primary endpoints were mortality rates at 14 and 30 days. Secondary endpoints were prognostic factors of 14-day mortality and overall graft loss. RESULTS: We enrolled 93 KTRs of which 75 were from Brazil. The mean time interval from transplantation to the onset of candidemia was 45.2 ± 61.5 months. 42% of all patients were on haemodialysis, 31.3% had an episode of sepsis and 39% underwent surgery within 30 days before fungemia. European patients were more likely to receive echinocandin (32 vs. 72%, p < .001). 22.7% of Brazilian patients did not receive any antifungal before death. All-cause mortality at 14 days was higher in Brazil (41.3 vs. 11.1%, p = .016). Candida colonisation (OR 6.91 [95% CI: 1.08-44.3], p = .042) and hypotension (OR 4.87 [95% CI: 1.62-14.66], p = .005) were associated with 14-day mortality. Echinocandin treatment had a protective effect (OR 0.19 [95% CI: 0.05-0.73], p = .015). Graft loss at 90 days occurred in 48% of patients (70.7 in Brazil vs. 22.2% in Europe, p < .01). CONCLUSIONS: Candidemia in KTR is usually documented late after engraftment in patients requiring HD, surgical procedures and dysbiosis secondary to antibiotic use. Mortality was higher in Brazil. Echinocandin therapy was associated with improved survival.

Real-World Clinical Experience of Dupilumab in the Treatment of Chronic Palmo-Plantar Eczema in Patients with Moderate-Severe Atopic Dermatitis: 52-Week Follow-Up.

Background: Hand-foot eczema (HFE) are special locations of dermatitis, which are often associated with atopic dermatitis (AD) and have a significant negative impact on the quality of life, demanding a clinically relevant improvement. Objectives: To evaluate the effectiveness and safety of dupilumab in the treatment of eczema localized in hands and/or feet in patients with moderate-to-severe AD. Methods: Retrospective multicenter study of adult patients with HFE treated with dupilumab for their AD. Patients with other concomitantly systemic immunosuppressive treatments did not undergo a washout period. The severity of palmar and/or plantar involvement was assessed using the Physician Global Assessment (PGA) scale on a scale of 0 ( = clear) to 5 ( = very severe). Eczema Area and Severity Index (EASI) and NRS-pruritus scales were also evaluated. One hundred percent of patients reached week 16, while 67/84 reached week 52 of follow-up. Results: A total of 84 patients were included 86.69% of patients showed a reduction in PGA-Hand, and 80.34% in PGA-Foot at week 52, EASI improvement was reached by 83.55% of patients at week 16 and 87.35% at week 52. Reduction of pruritus (≥4 points in NRS-pruritus scale) was 73.01% at week 16 and 80.67% at week 52. No differences in response to dupilumab were observed in the different subtypes of palmo-plantar dermatitis. Conclusions: The results obtained in our study suggest that dupilumab may be an effective and safe therapeutic option for the treatment of dermatitis localized in hands and/or feet.

Development of a Platform to Assess the Risk of Musculoskeletal Disorders in Manual Load Handling Activities - Preliminary Results.

Risk identification on workstations is a crucial step to prevent the occurrence of musculoskeletal disorders (MSD) in workers. The available methods and tools used by ergonomists to assess and estimate the risk related to manual handling of loads under repetitive work cycles are usually biased by the inter-evaluator error that can lead to a subjective determination of work-related risks due to the application of, mainly, observational methods. This paper shows the preliminary results of a platform to assess the risk of musculoskeletal disorders during manual load-handling tasks using an instrumented system and using the National Institute for Occupational Safety & Health (NIOSH) method. Eight healthy subjects were measured during lifting activities using an optical-based and inertial-based motion capture systems. The developed software implements a semi-automated instrumented version of the NIOSH method, helping the evaluator with automated calculations of body segment locations, displacements and joint angles making it possible to obtain a objective risk classification. Also, we achieved a reduction of 85% in the time for the estimation of the necessary factors for the digital evaluation methodology, making the proposed platform a promising and attractive alternative for its application in real environments for risk assessments.Occupational health relevance- This work proposes an assistance tool for the detection of musculoskeletal disorders in activities related to manual handling of loads, essential to initiate modification strategies in the workplace, reduce the occurrence of occupational diseases and reduce the time of risk classification.

Smartphone use in Neurology: a bibliometric analysis and visualization of things to come.

Background and objectives: Smartphones are a ubiquitous part of society with increasing use as a healthcare tool. We aimed to analyze the published literature on smartphone usage within the field of Neurology to define the scientific landscape and forecast future research initiatives. Methods: We performed a bibliometric review of smartphone uses in Neurology based on a search of two Web of Science databases from inception through September 16, 2022. This librarian-guided review was conducted using Bibliometrix for data assessment and visualization. Temporal trends in publications, citation counts, collaborations, and author affiliations were among key metrics evaluated. VOS viewer identified hot spots based on generating co-occurrences and bibliographic coupling mapping. Results: Our search found 3,920 publications. The U.S. produced the most topic-based publications, collaborating most frequently with U.K., Canada, and China-based authors. The most prolific institutions included Karolinska Institute, University of Sydney, and University of Pittsburgh. Bioelectromagnetics, Stroke, and Neurology were the most cited journals. Rapid growth in scientific production occurred in recent years, including during the COVID-19 pandemic. Hotspots and keyword co-occurrence included telehealth, machine learning, and self-management. Temporal trends reflect transitioning from a focus of initial publications regarding mobile phone safety to more recent application of smartphones as "smart" tools for single modality diagnosis, monitoring, management, and treatment of neurological diseases. Discussion: There has been rapid expansion of the published literature on smartphone uses in Neurology. Initial focus on smartphones and health risk has shifted to uses for neurological disease diagnosis, detection, and management, with relevance as a global interface for collaboration and clinical practice.

Is Non-Adherence Associated with Adverse Outcomes in Kidney Transplant Recipients? The Role of Non-Adherence as a Risk and Predictor Factor for Graft Loss and Death.

Introduction:  Non-adherence in kidney transplants is diversely defined. Immunosuppression non-adherence (INA) is the most used definition and has been associated with graft loss and acute rejection. But INA assesses only one fraction of adherence. Therefore, we analyzed the association of a holistic non-adherence definition with transplant outcomes and compared its prediction performance with other definitions. Methods:  We retrospectively included 739 kidney recipients between 2019 and 2021. We evaluated holistic non-adherence (HNA), suboptimal-immunosuppressor levels (SIL), appointment non-adherence (ANA), procedure non-adherence (PNA) and INA. The main outcomes were graft loss, graft rejection, and mortality. A backward logistic regression was performed estimating adjusted and un-adjusted odds ratio (OR) for each outcome. Finally, we compared the non-adherence definitions' prediction for the main outcomes using the area under the curve. Results: HNA was present in 28.7% of patients. Non-adherent patients had an adjusted OR of 2.66 (1.37-5.15) for mortality, 6.44 for graft loss (2.71-16.6), and 2.28 (1.15-4.47) for graft rejection. INA and PNA presented a moderate discrimination for graft loss and HNA and ANA mild-to-moderate discrimination for graft loss and death. Conclusion: Holistic non-adherence was associated with worst outcomes in kidney recipients and had a significant prediction performance for graft loss and mortality.

Cohabitation with aggressive hosts: description of a new microhisterid species in nests of a ponerine ant with ecological notes.

A new clown beetle species, Bacanius neoponerae, is described from Mexican nests of the arboreal ponerine ant Neoponera villosa found in the tank bromeliad Aechmea bracteata. Adult beetles were found in brood chambers or inner refuse piles, but also outside the ant nests, in decaying organic matter between the bromeliad leaves. No direct interactions between ants and microhisterid beetles could be observed. Several lines of evidence suggest a close relationship either with the ants, specific microhabitats within the ant nests or the bromeliads. Sample site elevation, colony size, monthly rainfall and collecting site were the main variables predicting the association. Almost half of the N. villosa colonies were associated with the microhisterids, and larger colonies favored their presence, especially during the driest months of the year. Two specimens were found in a nest of another ant species, Camponotus atriceps, also inhabiting A. bracteata. The new species is the seventh of the genus Bacanius reported from Mexico. This is the second time a species of this genus is associated with ants, and the fourth record of a histerid beetle cohabiting with ponerine ants. The small size of these beetles and their very protective body structure may facilitate their cohabitation with such aggressive hosts.

A Mini-Review of Enteroaggregative Escherichia coli with a Specific Target on the Virulence Factors Controlled by the AggR Master Regulator.

Enteroaggregative Escherichia coli (EAEC) strains have been linked to several outbreaks of severe diarrhea around the world, and this bacterium is now commonly resistant to antibiotics. As part of the pathophysiology of EAEC, the characteristic pattern of adherence looks like stacked bricks on the intestinal epithelium. This phenotype depends on an aggregative adhesion plasmid (pAA), which codes for a regulatory protein named AggR. The AggR protein is a master regulator that transcriptionally actives the main virulence genes in this E. coli pathotype, such as those that encode the aggregative adhesion fimbriae, dispersin and its secretion apparatus, Aar regulatory protein, and type VI secretion system. Several reports have shown that AggR positively affects most EAEC virulence genes, functioning as a classic transcriptional activator in the promoter region of these genes, interacting with the RNA polymerase. This minireview article integrates the information about virulence determinants of EAEC controlled by the AggR regulator.

Reliability of point-of-care ultrasound to evaluate fluid tolerance performed by critical care residents.

BACKGROUND: Patients with hypotension usually receive intravenous fluids, but only 50% will respond to fluid administration. We aimed to assess the intra and interobserver agreement to evaluate fluid tolerance through diverse ultrasonographic methods. METHODS: We prospectively included critically ill patients on mechanical ventilation. One trained intensivist and two intensive care residents obtained the left ventricular outflow tract velocity-time integral (VTI) variability, inferior vena cava (IVC) distensibility index, internal jugular vein (IJV) distensibility index, and each component of the venous excess ultrasound (VExUS) system. We obtained the intraclass correlation coefficient (ICC) and Gwet's first-order agreement coefficient (AC1), as appropriate. RESULTS: We included 32 patients. In-training observers were unable to assess the VTI-variability in two patients. The interobserver agreement was moderate to evaluate the IJV-distensibility index (AC1 0.54, CI 95% 0.29-0.80), fair to evaluate VTI-variability (AC1 0.39, CI 95% 0.12-0.66), and absent to evaluate the IVC-distensibility index (AC1 0.19, CI 95% - 0.07 to 0.44). To classify patients according to their VExUS grade, the intraobserver agreement was good, and the interobserver agreement was moderate (AC1 0.52, CI 95% 0.34-0.69). CONCLUSIONS: Point-of-care ultrasound is frequently used to support decision-making in fluid management. However, we observed that the VTI variability and IVC-distensibility index might require further training of the ultrasound operators to be clinically useful. Our findings suggest that the IJV-distensibility index and the VExUS system have acceptable reproducibility among in-training observers.

Utilizing Motion Capture Systems for Instrumenting the OCRA Index: A Study on Risk Classification for Upper Limb Work-Related Activities.

In the search to enhance ergonomic risk assessments for upper limb work-related activities, this study introduced and validated the efficiency of an inertial motion capture system, paired with a specialized platform that digitalized the OCRA index. Conducted in a semi-controlled environment, the proposed methodology was compared to traditional risk classification techniques using both inertial and optical motion capture systems. The inertial method encompassed 18 units in a Bluetooth Low Energy tree topology network for activity recording, subsequently analyzed for risk using the platform. Principal outcomes emphasized the optical system's preeminence, aligning closely with the conventional technique. The optical system's superiority was further evident in its alignment with the traditional method. Meanwhile, the inertial system followed closely, with an error margin of just ±0.098 compared to the optical system. Risk classification was consistent across all systems. The inertial system demonstrated strong performance metrics, achieving F1-scores of 0.97 and 1 for "risk" and "no risk" classifications, respectively. Its distinct advantage of portability was reinforced by participants' feedback on its user-friendliness. The results highlight the inertial system's potential, mirroring the precision of both traditional and optical methods and achieving a 65% reduction in risk assessment time. This advancement mitigates the need for intricate video setups, emphasizing its potential in ergonomic assessments.

Relationship of early brain growth pattern measured by ultrasound with neurological outcome at two years of age in very low birth weight infants.

The purpose of this study is to define the impact of early brain growth trajectory in very low birth weight infants (VLBWI) on neurological prognosis at 2 years, assessed using sequential ultrasound (US) scans. This is a prospective cohort study with consecutive inclusion of VLBWI ≤ 32 weeks gestational age and ≤ 1500 g at birth. Total brain volume (TBV) was assessed using sequential 3D-US from birth to discharge. Prognosis at 2 years (corrected age) was assessed using the Bayley Scales of Infant and Toddler Development Third Edition. TBV showed slower growth with postmenstrual age (PMA) in those VLBWI who had an adverse cognitive prognosis compared to those with good cognitive prognosis (mean difference in TBV between prognostic groups from 4.56 cm3 at 28 weeks to 42.58 cm3 at 43 weeks) as well as in those with adverse language prognosis (mean difference in TBV from 2.21 cm3 at 28 weeks to 26.98 cm3 at 43 weeks) although other variables showed more impact than TBV on language prognosis (gestational age at birth, brain injury at term, and socioeconomic status). No association was found between TBV and motor prognosis. Brain growth rate was also significantly higher in those VLBWI who presented good cognitive scores (18.78 + (0.33 × (PMA-33)) cm3/week) compared to those with adverse cognitive outcome (13.73 + (0.64 × (PMA-33)) cm3/week).  Conclusion: Early altered brain growth is associated with poor cognitive prognosis at 2 years of age. Using sequential US monitoring, we can detect early brain growth deviation in patients who will have adverse cognitive outcomes. What is known: • The prediction of neurodevelopmental outcome of VLBWI is mostly based on the presence of brain injury in US and structural magnetic resonance imaging (MRI) at term. • Some studies have related brain volume measured on MRI at term with neurodevelopment outcome. What is new: • VLBWI with adverse cognitive prognosis at two years of age present smaller brain volumes detectable by sequential US during NICU admission. • Brain volume can be estimated from 2D and 3D US and has prognostic value in VLBWI.

Multicenter Retrospective Andalusian Study of the Use of Sonidegib for the Treatment of Local Advanced Basal Cell Carcinoma in Real Clinical Practice.

INTRODUCTION: Locally advanced basal cell carcinoma (LA-BCC) is defined as that BCC in which there is radiological confirmation of invasion of certain neighboring structures in depth and also, usually, a BCC that is of a sufficient size and invasion (although there is no radiological demonstration of deep invasion) in which surgery and radiotherapy are not adequate, are insufficient or are contraindicated to achieve the cure of the tumor, either due to characteristics of the tumor itself or of the patient. Sonidegib is indicated for the treatment of adult patients with locally advanced basal cell carcinoma that is not amenable to curative surgery or radiotherapy. MATERIAL AND METHODS: This is a retrospective, multicenter and descriptive study in nine centers in Andalusia, Spain. Patients treated with sonidegib for >3 months for locally advanced BCC were included from 1 January 2021 to 1 January 2023. Epidemiological, efficacy and safety data were collected. RESULTS: In the present study, a total of 38 patients were included, with a median age of 76.23 years (range 40-101). Prior treatment was surgery (31.57%; n = 25), radiotherapy (15.78%; n = 6), vismodegib (31.57%; n = 12). Eleven patients had not received prior treatment. LA-BCC were located in the cephalic pole, face or scalp. There was a total response in 9/38 patients (23.7%), partial response in 25/38 patients (65.8%) and no response in 4 patients (10.52%). In 6/34 patients, the dose was reduced to 200 mg every other day until it was discontinued due to adverse effects. The main adverse effects reported were dysgeusia (n = 8), asthenia (n = 8), = 6), muscle spasms (n = 6), alopecia (n = 4) and gastrointestinal intolerance (n = 4). DISCUSSION: Sonidegib is the second iHh authorized for the treatment of adult patients with locally advanced BCC who are not amenable to curative surgery or radiotherapy, based on the results of the phase II clinical trial, BOLT. Sonidegib shows good effectiveness and an acceptable safety profile in routine clinical practice in the sample presented.

Prevalence and Modifiable Factors for Holistic Non-Adherence in Renal Transplant Patients: A Cross-Sectional Study.

Introduction: In renal transplant recipients, compliance with medical therapy is vital. Non-adherence is considered a risk factor for worst outcomes in kidney recipients, with attributed outcomes of 64% for graft loss and 80% for late acute rejection. Most literature defines adherence as self-based immunosuppression compliance but does not consider other relevant factors such as consult and procedure compliance. Therefore, this study aims to describe adherence prevalence in kidney transplant recipients and the factors related to non-adherence. Methods: This cross-sectional study included 1030 renal transplant patients followed by Colombiana de Trasplantes between January 2019 and July 2021. Sociodemographic and clinical variables were obtained based on clinical records. The mental-health group diagnosed holistic adherence in a semi-structured interview. The diagnosis considered medication intake failure, frequency and number of failures to medical controls or other procedures, suspicious non-adherence behaviors, and serum levels of immunosuppressants. A bivariate followed a descriptive analysis, and a forward logistic regression was performed for non-adherence. Results: Patients had a median of 47 years, and 58.1% were male. Non-adherence was presented in 30.7% of patients. The non-adherence patients were younger, with a higher prevalence of males, single, divided transplant care, had a longer time after transplantation, psychopathological diagnosis, and more reinforcement education by only nursing. Older age and multidisciplinary reinforcement education were protective factors. On the other hand, poor social support, psychopathology diagnosis, and longer time after transplant presented as non-adherence risk factors. Conclusion: Holistic non-adherence was diagnosed in approximately one-third of renal transplant recipients. Its definition included more than just medication non-compliance and could identify more non-adherent patients. Notably, there is a need to consider the related factors in the health follow-up and encourage future research in modifiable factor interventions aiming to increase adherence and achieve better outcomes for renal transplant patients.

Slow flow mimicking pulmonary embolism.

A man in his 70s in a rehabilitation hospital, post cerebral infarct, became acutely short of breath with reduced oxygen saturations and an elevated d-dimer.Non-occlusive filling defects were noted on the CT pulmonary angiogram in the proximal left pulmonary arteries. There was associated hypoplasia of the distal pulmonary arterial tree in the left hemithorax with left pulmonary vein stenosis. Review of previous imaging suggested this oligaemia was longstanding.Although filling defects in the pulmonary arteries usually correspond to embolic material, in our patient they were too dense to represent thrombus and probably represented flow-related artefacts in the setting of chronic air trapping.Given the associated volume loss, bronchiectasis and bronchial wall thickening in the left hemithorax Swyer-James-McLeod syndrome was thought to be the most likely underlying cause.

Molecular insights using spatial transcriptomics of the distal lung in congenital diaphragmatic hernia.

Abnormal pulmonary vascular development and function in congenital diaphragmatic hernia (CDH) is a significant factor leading to pulmonary hypertension. The lung is a very heterogenous organ and has marked cellular diversity that is differentially responsive to injury and therapeutic agents. Spatial transcriptomics provides the unmatched capability of discerning the differences in the transcriptional signature of these distinct cell subpopulations in the lung with regional specificity. We hypothesized that the distal lung parenchyma (selected as a region of interest) would show a distinct transcriptomic profile in the CDH lung compared with control (normal lung). We subjected lung sections obtained from male and female CDH and control neonates to spatial transcriptomics using the Nanostring GeoMx platform. Spatial transcriptomic analysis of the human CDH and control lung revealed key differences in the gene expression signature. Increased expression of alveolar epithelial-related genes (SFTPA1 and SFTPC) and angiogenesis-related genes (EPAS1 and FHL1) was seen in control lungs compared with CDH lungs. Response to vitamin A was enriched in the control lungs as opposed to abnormality of the coagulation cascade and TNF-alpha signaling via NF-kappa B in the CDH lung parenchyma. In male patients with CDH, higher expression of COL1A1 (ECM remodeling) and CD163 was seen. Increased type 2 alveolar epithelial cells (AT-2) and arterial and lung capillary endothelial cells were seen in control lung samples compared with CDH lung samples. To the best of our knowledge, this is the first use of spatial transcriptomics in patients with CDH that identifies the contribution of different lung cellular subpopulations in CDH pathophysiology and highlights sex-specific differences.NEW & NOTEWORTHY This is the first use of spatial transcriptomics in patients with congenital diaphragmatic hernia (CDH) that identifies the contribution of different lung cellular subpopulations in CDH pathophysiology and highlights sex-specific differences.

Modulation of Recovery from Neonatal Hyperoxic Lung Injury by Sex as a Biological Variable.

Recovery from lung injury during the neonatal period requires the orchestration of many biological pathways. The modulation of such pathways can drive the developing lung towards proper repair or persistent maldevelopment that can lead to a disease phenotype. Sex as a biological variable can regulate these pathways differently in the male and female lung exposed to neonatal hyperoxia. In this study, we assessed the contribution of cellular diversity in the male and female neonatal lung following injury. Our objective was to investigate sex and cell-type specific transcriptional changes that drive repair or persistent injury in the neonatal lung and delineate the alterations in the immune-endothelial cell communication networks using single cell RNA sequencing (sc-RNAseq) in a murine model of hyperoxic injury. We generated transcriptional profiles of >55,000 cells isolated from the lungs of postnatal day 1 (PND 1) and postnatal day 21 (PND 21) neonatal male and female C57BL/6 mice exposed to 95% FiO 2 between PND 1-5 (saccular stage of lung development). We show the presence of sex-based differences in the transcriptional states of lung endothelial and immune cells at PND 1 and PND 21. Furthermore, we demonstrate that biological sex significantly influences the response to injury, with a greater number of differentially expressed genes showing sex-specific patterns than those shared between male and female lungs. Pseudotime trajectory analysis highlighted genes needed for lung development that were altered by hyperoxia. Finally, we show intercellular communication between endothelial and immune cells at saccular and alveolar stages of lung development with sex-based biases in the crosstalk and identify novel ligand-receptor pairs. Our findings provide valuable insights into the cell diversity, transcriptional state, developmental trajectory, and cell-cell communication underlying neonatal lung injury, with implications for understanding lung development and possible therapeutic interventions while highlighting the crucial role of sex as a biological variable.