Arterial vascularization of the mandible and soft tissues. Anatomic study.

PURPOSE: The literature has for too long described the arterial supply of the mandible as coming from a single artery, the inferior alveolar artery, and being of the terminal type. Rather, it appears to come from an extensive and complex arterial network dependent on the lingual, facial, and maxillary arteries and their collateral branches. Our study aims to confirm and demonstrate the arterial vascular richness of the mandible and to establish arterial mapping. METHODS: The arterial vascularization of the mandible was revealed in six anatomic specimens after performing selective injections of the lingual, facial, and maxillary arteries with different dyes. A specimen was injected intra-arterially with colored latex at the level of the maxillary artery for a morphometric study. RESULTS: Eighteen selective arterial injections were performed on six anatomic specimens. The mucocutaneous, musculoperiosteal, and intramedullary vascularizations were analyzed. Each of the arteries has a defined and delimited cutaneo-mucous vascular territory. The facial and maxillary arteries supply the musculoperiosteal vascularization of the mandible from the condyle to the symphysis. The lingual artery supplies only the inner cortex of the parasymphyseal and symphyseal regions. The facial and maxillary arteries provide intramedullary vascularization from the angle of the mandible to the parasymphysis. The vascularization of the symphysis depends on the facial artery. No staining was found in the condyle region. Neoprene latex injection was performed on an anatomic specimen, revealing a permeable anastomosis between the inferior alveolar and facial arteries. CONCLUSION: The arterial vascularization of the mandible is dependent on the maxillary, facial, and lingual arteries. This is a network vasculature. This study makes it possible to establish an arterial map of the mandible. The presence of an anastomosis between the inferior alveolar artery and the facial artery confirms the existence of dynamic and borrowed vascularization. Knowledge of this arterial system makes it possible to adapt maxillofacial surgical care and to anticipate possible intraoperative complications.

First-line therapy with palbociclib in patients with advanced HR+/HER2- breast cancer: The real-life study PALBOSPAIN.

PURPOSE: To evaluate the efficacy and safety of first-line therapy with palbociclib in a Spanish cohort treated after palbociclib approval. METHODS: PALBOSPAIN is an observational, retrospective, multicenter study evaluating real-world patterns and outcomes with 1 L palbociclib in men and women (any menopausal status) with advanced HR+/HER2- BC diagnosed between November 2017 and November 2019. The primary endpoint was real-world progression-free survival (rw-PFS). Secondary endpoints included overall survival (OS), the real-world response rate (rw-RR), the clinical benefit rate, palbociclib dose reduction, and safety. RESULTS: A total of 762 patients were included. The median rw-PFS and OS were 24 months (95% CI 21-27) and 42 months (40-not estimable [NE]) in the whole population, respectively. By cohort, the median rw-PFS and OS were as follows: 28 (95% CI 23-39) and 44 (95% CI 38-NE) months in patients with de novo metastatic disease, 13 (95% CI 11-17) and 36 months (95% CI 31-41) in patients who experienced relapse < 12 months after the end of ET, and 31 months (95% CI 26-37) and not reached (NR) in patients who experienced relapse > 12 months after the end of ET. rw-PFS and OS were longer in patients with oligometastasis and only one metastatic site and those with non-visceral disease. The most frequent hematologic toxicity was neutropenia (72%; grade ≥ 3: 52.5%), and the most common non-hematologic adverse event was asthenia (38%). CONCLUSION: These findings, consistent with those from clinical trials, support use of palbociclib plus ET as 1 L for advanced BC in the real-world setting, including pre-menopausal women and men. TRIAL REGISTRATION NUMBER: NCT04874025 (PALBOSPAIN). Date of registration: 04/30/2021 retrospectively registered.

The influence of age, period, and cohort factors on the incidence of kidney cancer in Spain 1990-2019: Evidence from the global burden of disease study.

OBJECTIVE: This study aimed to assess the influence of age, period, and cohort (A-P-C) factors on kidney cancer (KC) incidence trends in Spain from 1990 to 2019. METHODS: Employing data from the Global Burden of Disease Study 2019, we employed joinpoint analysis to determine long-term patterns and A-P-C modelling to quantify net drift, local drift, longitudinal age curves, and rate ratios (RRs) of period and cohort effects. RESULTS: Over the period 1990-2019, an estimated 142,811 cases of KC were diagnosed in Spain. A consistent upward trend in KC incidence was observed for both men and women, with the male-to-female ratio remaining stable at 2.6. Joinpoint analysis identified three distinct periods for men: An initial period (1990-1995) characterised by a significant increase in rates, a subsequent period (1995-2016) characterised by a slowdown in the rate of increase, and a final period (2016-2019) in which rates have plateaued. In women, 2 time periods were observed: an initial period (1990-2007) in which rates increased significantly, followed by a period of stabilization (2007-2019). Men born in the early-mid 20th century had a rising KC risk, peaking in the 1960s. Women's risk rose steadily, peaking in the late 1990s. CONCLUSION: A-P-C analysis reveals steady KC incidence increase in both genders over three decades. This highlights the need for targeted public health policies and effective prevention strategies.

Long-term results with biosynthetic absorbable P4HB mesh in ventral abdominal wall repair: a multicentre analysis.

BACKGROUND: The aim of this multicentre study was to analyse the outcomes of biosynthetic absorbable poly-4-hydroxybutyrate (P4HB) prosthesis implantation in patients undergoing ventral hernia repair (VHR) in the context of different degrees of contamination. METHODS: From May 2016 to December 2021, a multicentre retrospective analysis of patients who underwent elective or urgent hernia repair with P4HB prosthesis was performed in seven hospitals in Spain and Portugal. Patients with a postoperative follow-up of less than 20 months and those within the theoretical period of prosthesis resorption were excluded from the study. Regarding the degree of contamination, patients were assessed according to the modified Ventral Hernia Working Group (VHWG) classification. Epidemiological data, hernia characteristics, surgical and postoperative variables (Clavien-Dindo classification) of these patients were analyzed. Risk factors related to long-term recurrence were studied by a multivariate analysis. RESULTS: In 236 cases of P4HB prosthesis implantation, repair in cases of Grade 3 was the most frequent (49.1%), followed by Grade 2 in 42.3% of cases and Grade 1 in 8.4%. The most frequent complications were Grade 1, with the majority occurring during the first year. The overall rate of surgical site occurrences (SSO) was 30%. The hernia recurrence rate was 14.4% (n = 34), with a mean postoperative follow-up time of 41 months (22-61). The multivariate analysis showed that the onlay location of the mesh (OR 1.07; CI 1.42-2.70, p = 0.004) was a significant independent risk factor for recurrence. CONCLUSIONS: The use of a P4HB bioresorbable mesh for the VHR with different degrees of contamination leads to favourable results overall, with an acceptable rate of hernia recurrence. The onlay location of the P4HB prosthesis is the main factor in recurrence in both elective and emergency settings.

The management of paediatric acute pain in Spain in 2021: Results of a national survey among paediatric anaesthesiologists.

OBJECTIVE: To improve knowledge about routine clinical practice in the management of paediatric acute pain in Spain. METHODS: A telematic survey was conducted via the Internet on a representative sample of healthcare professionals involved in the management of paediatric acute pain (specifically anaesthesiologists) in Spain. The survey included 28 questions about their usual clinical practice in the assessment and treatment of acute pain, and also training and organisational aspects in paediatric acute pain. RESULTS: The survey was completed during March 2021 by 150 specialists in anaesthesiology. The respondents widely experienced in the management of acute paediatric pain (mean years of experience: 14.3: SD: 7.8), essentially in acute postoperative pain (97% of cases). Although 80% routinely used validated paediatric acute pain assessment scales, only 2.6% used specific scales adapted for patients with cognitive impairment. Most of the respondents routinely used analgesic drugs such as paracetamol (99%) or metamizole (92%), but only 84% complemented these drugs with a loco-regional blocking technique or other non-steroidal anti-inflammatory drugs (62%). Furthermore, only 62.7% acknowledged having received specific training in paediatric acute pain, only 45% followed hospital institutional protocols, and a scant 28% did so through paediatric pain units. CONCLUSIONS: The survey identified important points for improvement in the training and organisation of acute pain management in Spanish paediatric patients.

An explainable machine learning approach for hospital emergency department visits forecasting using continuous training and multi-model regression.

BACKGROUND AND OBJECTIVE: In the last years, the Emergency Department (ED) has become an important source of admissions for hospitals. Since late 90s, the number of ED visits has been steadily increasing, and since Covid19 pandemic this trend has been much stronger. Accurate prediction of ED visits, even for moderate forecasting time-horizons, can definitively improve operational efficiency, quality of care, and patient outcomes in hospitals. METHODS: In this paper we propose two different interpretable approaches, based on Machine Learning algorithms, to accurately forecast hospital emergency visits. The proposed approaches involve a first step of data segmentation based on two different criteria, depending on the approach considered: first, a threshold-based strategy is adopted, where data is divided depending on the value of specific predictor variables. In a second approach, a cluster-based ensemble learning is proposed, in such a way that a clustering algorithm is applied to the training dataset, and ML models are then trained for each cluster. RESULTS: The two proposed methodologies have been evaluated in real data from two hospital ED visits datasets in Spain. We have shown that the proposed approaches are able to obtain accurate ED visits forecasting, in short-term and also long-term prediction time-horizons up to one week, improving the efficiency of alternative prediction methods for this problem. CONCLUSIONS: The proposed forecasting approaches have a strong emphasis on providing explainability to the problem. An analysis on which variables govern the problem and are pivotal for obtaining accurate predictions is finally carried out and included in the discussion of the paper.

A dynamical measure of the black hole mass in a quasar 11 billion years ago.

Tight relationships exist in the local Universe between the central stellar properties of galaxies and the mass of their supermassive black hole (SMBH)1-3. These suggest that galaxies and black holes co-evolve, with the main regulation mechanism being energetic feedback from accretion onto the black hole during its quasar phase4-6. A crucial question is how the relationship between black holes and galaxies evolves with time; a key epoch to examine this relationship is at the peaks of star formation and black hole growth 8-12 billion years ago (redshifts 1-3)7. Here we report a dynamical measurement of the mass of the black hole in a luminous quasar at a redshift of 2, with a look back in time of 11 billion years, by spatially resolving the broad-line region (BLR). We detect a 40-µas (0.31-pc) spatial offset between the red and blue photocentres of the Hα line that traces the velocity gradient of a rotating BLR. The flux and differential phase spectra are well reproduced by a thick, moderately inclined disk of gas clouds within the sphere of influence of a central black hole with a mass of 3.2 × 108 solar masses. Molecular gas data reveal a dynamical mass for the host galaxy of 6 × 1011 solar masses, which indicates an undermassive black hole accreting at a super-Eddington rate. This suggests a host galaxy that grew faster than the SMBH, indicating a delay between galaxy and black hole formation for some systems.

Evolution of chromium and cobalt serum levels after the use of a modular neck stem in primary total hip arthroplasty. / Evolución de los niveles séricos de cromo y cobalto tras el empleo de un vástago con cuello modular en la artroplastia total de cadera primaria.

INTRODUCTION AND OBJECTIVES: Modular neck primary stems were introduced with the theoretical advantage of restoring the hip anatomy more precisely. However, the presence of a second junction has been associated with increased corrosion and release of metal debris. The objective of our study is to quantify of chromium and cobalt serum values, and to analyze their temporal evolution during five years. MATERIAL AND METHODS: We present a prospective series of 61 patients who underwent primary total hip arthroplasty by implantation of the HMAX-M® stem (Limacorporate, San Daniele, Italy). Serum chromium and cobalt determinations were performed at six months, two years and five years. RESULTS: Our series shows a progressive elevation in chromium levels with a significant difference between chromium values at six months (0.35±0.18) and five years (0.52±0.36), P=.01. Regarding cobalt, a statistically significant elevation is observed between six months and two years and a subsequent stabilization of values between two and five years, with a cobalt mean at six months (1.17±0.8) significantly lower than at two (2.63±1.76) and five years (2.84±2.1), P=.001. CONCLUSION: Elevated serum cobalt levels have been observed in patients who underwent modular neck stem implantation. The results obtained in this study have limited the use of stems with a modular neck in our clinical practice.

[Translated article] Evolution of chromium and cobalt serum levels after the use of a modular neck stem in primary total hip arthroplasty.

INTRODUCTION AND OBJECTIVES: Modular neck primary stems were introduced with the theoretical advantage of restoring the hip anatomy more precisely. However, the presence of a second junction has been associated with increased corrosion and release of metal debris. The objective of our study is to quantify of chromium and cobalt serum values, and to analyse their temporal evolution during five years. MATERIAL AND METHODS: We present a prospective series of 61 patients who underwent primary total hip arthroplasty by implantation of the H MAX-M® stem (Limacorporate, San Daniele, Italy). Serum chromium and cobalt determinations were performed at six months, two years and five years. RESULTS: Our series shows a progressive elevation in chromium levels with a significant difference between chromium values at six months (0.35±0.18) and five years (0.52±0.36), p=.01. Regarding cobalt, a statistically significant elevation is observed between six months and two years and a subsequent stabilisation of values between two and five years, with a cobalt mean at six months (1.17±0.8) significantly lower than at two (2.63±1.76) and five years (2.84±2.1), p=.001. CONCLUSION: Elevated serum cobalt levels have been observed in patients who underwent modular neck stem implantation. The results obtained in this study have limited the use of stems with a modular neck in our clinical practice.

ClO-driven degradation of graphene oxide: new insights from DFT calculations.

We present an extensive investigation using density functional theory (DFT) calculations on various model graphene oxide (GO) nanostructures interacting with chlorine monoxide ClO, aiming to understand the role of this highly oxidizing species in C-C bond breakage and the formation of significant holes on GO sheets. During its function, the myeloperoxidase (MPO) enzyme abundantly generates chlorine-oxygen-containing species and their presence has been identified as the cause of degradation in carbon nanotubes of diverse sizes, morphologies, and chemical compositions, both in in vivo and in vitro samples. Notably, Kurapati et al. (Small, 2015, 11, 3985-3994) demonstrated efficient degradation of single GO monolayers through MPO catalysis, though the exact degradation mechanism remains unclear. In our study, we discover that breaking C-C bonds in a single graphene oxide sheet is achievable through a simple mechanism involving the dissociation of two ClO molecules that are chemically attached as nearest neighbor species but bonded to opposite sides of the GO layer (up/down configuration). Two new carbonyl oxygens appear on the surface and the Cl atoms can be transferred to the carbon layer or as physisorbed species near the GO surface. Relatively small energy barriers are associated with these molecular events. Continuing this process on neighboring sites leads to the presence of larger holes on the GO surface, accompanied by an increase in carbonyl species on the carbon network, consistent with X-ray photoelectron spectroscopy measurements. Indeed, the distribution of oxygen functionalities is found to be crucial in defining the damage pattern induced in the carbon layer. We emphasize the important role played by the local charge distribution in the stability or instability of chemical bonds, as well as in the energy barriers and reaction pathways. Finally, we explore the possibility of achieving chlorination of GO following MPO exposure. The here-reported predictions could be the root cause of the experimentally observed low stability of individual GO sheets during the MPO catalytic cycle.

Influence of Taper surface topographies on contact deformation and stresses.

The role of bore and trunnion surface topography on the failure rate of total hip joint replacements due to trunnionosis is not clear despite significant variations in the design of taper components between manufacturers. Taper surface topography, along with other taper design parameters such as clearance, diameter, and assembly force, determine the initial interlock of the contacting surfaces after assembly; this has been related to relative motions that can cause fretting and corrosion at the taper interface. However, in most in-silico parametrical taper studies associated with taper micromotions, the bore and trunnion surfaces have been simplified using a flat surface and/or sinusoidal functions to mimic the surface roughness. The current study tests the hypothesis that the use of simple geometrical functions for the taper surface topography can predict the surface mechanics developed in assembled tapers. Measured and simulated surfaces of bores and trunnions were characterised using common roughness parameters and spectral density estimations. Using the same characterised surface profiles, 2D Finite Element (FE) models of CoCr alloy femoral heads and Ti alloy trunnions were developed. Models simulated assembly conditions at different resultant forces ranging from 0.5 to 4.0 kN, contact conditions were determined and associated with their topographical characteristics. Measured surfaces of bore and trunnion components comprise up to seven dominant spatial frequencies. Flattening of the trunnion microgrooved peaks was observed during the assembly of the taper. When the femoral head bore and trunnion topography were both considered a reduced number of microgrooved peaks were in contact, from 51 in an idealised taper surfaces to 35 in measured surfaces using an assembly reaction force of 4 kN. The contact points in the models developed high plastic strains, which were greater than that associated with failure of the material. Results showed that line and sine wave functions over estimate contact points at the taper interface compared to those surfaces that consider roughness and peak variation. These findings highlight the important role of modelling the full surface topography on the taper contact mechanics, as surface variations in the roughness and waviness change the performance of tapers.

Immunotherapy in patients with brain metastasis: advances and challenges for the treatment and the application of circulating biomarkers.

The central nervous system (CNS) is one of the most frequent metastatic sites of various cancers, including lung cancer, breast cancer and melanoma. The development of brain metastases requires a specific therapeutic approach and is associated with high mortality and morbidity in cancer patients. Advances in precision medicine and the introduction in recent years of new drugs, such as immunotherapy, have made it possible to improve the prognosis of these patients by improving survival and quality of life. New diagnostic techniques such as liquid biopsy allow real-time monitoring of tumor evolution, providing molecular information on prognostic and predictive biomarkers of response to treatment in blood or other fluids. In this review, we perform an exhaustive update of the clinical trials that demonstrate the utility of immunotherapy in patients with brain metastases and the potential of circulating biomarkers to improving the results of efficacy and toxicity in this subgroup of patients.

Nocturnal agitation: From sleep state dissociation to sleep-related dissociative state.

Nocturnal agitation refers to a broad spectrum of symptoms from simple movements to aggressive behaviors with partial or complete loss of awareness. An accurate identification of its etiology is critical for appropriate therapeutic intervention. In children and young adults, distinguishing between non-rapid eye movement (NREM) sleep parasomnias and psychogenic non-parasomniac manifestations, a condition known as sleep-related dissociative disorder (SRDD), can be challenging. This review aims to summarize current clinical, neurophysiological, and epidemiological knowledge on NREM parasomnia and SRDD, and to present the pathophysiological hypotheses underlying these nocturnal manifestations. Sleepwalking, sleep terror and confusional arousals are the three main presentations of NREM parasomnias and share common clinical characteristics. Parasomniac episodes generally occur 30minutes to three hours after sleep-onset, they are usually short, lasting no more than few minutes and involve non-stereotyped, clumsy behaviors with frequent amnesia. The prevalence of NREM parasomnia decreases from 15-30% in children to 2-4% in adults. Parasomniac episodes are incomplete awakening from the deepest NREM sleep and are characterized by a dissociated brain activity, with a wake-like activation in motor and limbic structures and a preserved sleep in the fronto-parietal regions. SRDD is a less known condition characterized by dramatic, often very long episodes with frequent aggressive and potentially dangerous behaviors. SRDD episodes frequently occur in quiet wakefulness before falling asleep. These dissociative manifestations are frequently observed in the context of psychological trauma. The pathophysiology of SRDD is poorly understood but could involve transient changes in brain connectivity due to labile sleep-wake boundaries in predisposed individuals. We hypothesize that SRDD and NREM parasomnia are forms of sleep-related dissociative states favored by a sleep-wake state dissociation during sleep-onset and awakening process, respectively.

Evaluation of hypersomnolence: From symptoms to diagnosis, a multidimensional approach.

Hypersomnolence is a major public health issue given its high frequency, its impact on academic/occupational functioning and on accidentology, as well as its heavy socio-economic burden. The positive and aetiological diagnosis is crucial, as it determines the therapeutic strategy. It must consider the following aspects: i) hypersomnolence is a complex concept referring to symptoms as varied as excessive daytime sleepiness, excessive need for sleep, sleep inertia, or drowsiness, all of which warrant specific dedicated investigations; ii) the boundary between physiological and abnormal hypersomnolence is blurred, since most symptoms can be encountered in the general population to varying degrees without being considered as pathological, meaning that their severity, frequency, context of occurrence and related impairment need to be carefully assessed; iii) investigation of hypersomnolence relies on scales/questionnaires as well as behavioural and neurophysiological tests, which measure one or more dimensions, keeping in mind the possible discrepancy between objective and subjective assessment; iv) aetiological reasoning is driven by knowledge of the main sleep regulation mechanisms, epidemiology, and associated symptoms. The need to assess hypersomnolence is growing, both for its management, and for assessing the efficacy of treatments. The landscape of tools available for investigating hypersomnolence is constantly evolving, in parallel with research into sleep physiology and technical advances. These investigations face the challenges of reconciling subjective perception and objective data, making tools accessible to as many people as possible and predicting the risk of accidents.

Clinical, molecular, and immune correlates of the Immunotherapy Response Score in patients with advanced urothelial carcinoma under atezolizumab monotherapy: analysis of the phase II IMvigor210 trial.

BACKGROUND: In the advanced urothelial carcinoma (aUC) scenario there are no consistent immune checkpoint blockade predictive biomarkers. Recently a novel pan-tumor molecular tissue-based biomarker, the Immunotherapy Response Score (IRS), has been proposed. We conducted a retrospective study to validate the prognostic/predictive utility of the IRS in patients with aUC under atezolizumab monotherapy and to characterize its underlying molecular/immune features in the context of the IMvigor210 phase II trial. PATIENTS AND METHODS: This is a post hoc pooled analysis of 261 patients with available clinical, molecular, and immune tumor data treated with atezolizumab monotherapy in the IMvigor210 phase II clinical trial. Efficacy endpoints were overall survival (OS), disease control rate (DCR), and overall response rate (ORR). Survival estimates were calculated by the Kaplan-Meier method, and groups were compared with the log-rank test. The Cox proportional hazards regression model was used to evaluate factors independently associated with OS. Factors associated with disease control (DC) and response were tested with logistic regression in univariable and multivariable analyses. Comparisons between patient and disease characteristics were carried out using chi-square or Fisher's exact tests. All P values were two-sided, and those <0.05 were considered statistically significant. RESULTS: High IRS was significantly associated with a better OS in univariable [hazard ratio (HR) = 0.49, P < 0.001] and multivariable (HR = 0.60, P = 0.018) analyses. DCR and ORR were significantly higher among high IRS patients (DCR for high IRS versus low IRS patients: 57% versus 32%, P < 0.001; ORR: 42% versus 10%, P < 0.001). High IRS patients presented a higher probability of DC and response in univariable [DC: odds ratio (OR) = 2.72, P < 0.001; response: OR = 3.92, P < 0.001] and multivariable (DC: OR = 2.72, P < 0.001; response: OR = 3.92, P < 0.001) analyses. CONCLUSIONS: This study validates IRS as a strong independent prognostic and predictive biomarker for OS and DC/response in patients with aUC treated with atezolizumab monotherapy in the IMvigor210 phase II clinical trial.

Detecting and characterizing special nuclear material for nuclear nonproliferation applications.

There is an urgent need for new, better instrumentation and techniques for detecting and characterizing special nuclear material (SNM), i.e., highly enriched uranium and plutonium. The development of improved instruments and techniques requires experiments performed with the SNM itself, which is of limited availability. This paper describes the findings of experiments performed at the National Criticality Experiments Research Center conducted using new instruments and techniques on unclassified, kg-quantity SNM objects. These experiments, performed in the framework of the Department of Energy, National Nuclear Security Administration Consortium for Monitoring, Technology, and Verification, focused on detecting, characterizing, and localizing SNM samples with masses ranging from 3.3 to 13.8 kg, including plutonium and highly enriched uranium using prototype detectors and techniques. The work demonstrates SNM detection and characterization using recently-developed prototype detection systems. Specifically, we present new results in passive detection and imaging of plutonium and uranium objects using gamma-ray and dual particle (fast neutron and gamma-ray) imaging. We also present a new analysis of the delayed neutron emissions during active interrogation of uranium using a neutron generator.