Left atrial appendage occlusion for atrial fibrillation and bleeding diathesis.

BACKGROUND: Patients with atrial fibrillation (AF) and likelihood of bleeding can undergo left atrial appendage occlusion (LAAO) as an alternative method of stroke prophylaxis. Short-term anti-thrombotic drugs are used postprocedure to offset the risk of device-related thrombus, evidence for this practice is limited. OBJECTIVES: To investigate optimal postimplant antithrombotic strategy in high bleeding-risk patients. METHODS: Patients with AF and high-risk for both stroke and bleeding undergoing LAAO were advised their perioperative drug therapy by a multidisciplinary physician panel. Those deemed to be at higher risk of bleeding from anti-thrombotic drugs were assigned to minimal treatment with no antithrombotics or Aspirin-alone. The remaining patients received standard care (STG) with a 12 week course of dual-antiplatelets or anticoagulation postimplant. We compared mortality, device-related thrombus, ischemic stroke, and bleeding events during the 90 days postimplant and long-term. Event-free survival was assessed using Kaplan-Meier survival analysis, with logrank testing for statistical significance. RESULTS: Seventy-five patients underwent LAAO of whom 63 patients (84%) had a prior serious bleeding event. The 42 patients on minimal treatment were older (74.3 ± 7.7 vs. 71.2 ± 7.2) with higher HASBLED score (3.6 ± 0.9 vs. 3.3 ± 1.2) than the 33 patients having standard care. There were no device-related thrombi or strokes in either group at 90 days postprocedure; STG had more bleeding events (5/33 vs. 0/42, p = 0.01) with associated deaths (3/33 vs. 0/42, p = 0.05). During long-term follow-up (median 2.2 years), all patients transitioned onto no antithrombotic drugs (43 patients [61%]) or a single-antiplatelet (29 patients [39%]). There was no evidence of early minimal treatment adversely affecting long-term outcomes. CONCLUSIONS: Short-term anti-thrombotic drugs may not be needed after LAAO implant in patients with high bleeding risk and could be harmful. Larger, prospective studies would be warranted to test these findings.

Circulating epigenomic biomarkers correspond with kidney disease susceptibility in high-risk populations with type 2 diabetes mellitus.

AIMS: To investigate epigenomic indices of diabetic kidney disease (DKD) susceptibility among high-risk populations with type 2 diabetes mellitus. METHODS: KDIGO (Kidney Disease: Improving Global Outcomes) clinical guidelines were used to classify people living with or without DKD. Differential gene methylation of DKD was then assessed in a discovery Aboriginal Diabetes Study cohort (PROPHECY, 89 people) and an external independent study from Thailand (THEPTARIN, 128 people). Corresponding mRNA levels were also measured and linked to levels of albuminuria and eGFR. RESULTS: Increased DKD risk was associated with reduced methylation and elevated gene expression in the PROPHECY discovery cohort of Aboriginal Australians and these findings were externally validated in the THEPTARIN diabetes registry of Thai people living with type 2 diabetes mellitus. CONCLUSIONS: Novel epigenomic scores can improve diagnostic performance over clinical modelling using albuminuria and GFR alone and can distinguish DKD susceptibility.

Clinical trait-specific genetic analysis in Behçet's disease identifies novel loci associated with ocular and neurological involvement.

Behçet's disease is a complex inflammatory vasculitis with a broad spectrum of clinical manifestations. The purpose of this study was to investigate the genetics underlying specific clinical features of Behçet's disease. A total of 436 patients with Behçet's disease from Turkey were studied. Genotyping was performed using the Infinium ImmunoArray-24 BeadChip. After imputation and quality control measures, logistic regressions adjusting for sex and the first five principal components were performed for each clinical trait using a case-case genetic analysis approach. A weighted genetic risk score was calculated for each clinical feature. Genetic association analyses of previously identified susceptibility loci in Behçet's disease revealed a genetic association between ocular lesions and HLA-B/MICA (rs116799036: OR = 1.85 [95% CI = 1.35-2.52], p-value = 1.1 × 10-4). The genetic risk score was significantly higher in Behçet's disease patients with ocular lesions compared to those without ocular involvement, which is explained by the genetic variation in the HLA region. New genetic loci predisposing to specific clinical features in Behçet's disease were suggested when genome-wide variants were evaluated. The most significant associations were observed in ocular involvement with SLCO4A1 (rs6062789: OR = 0.41 [95% CI = 0.30-0.58], p-value = 1.92 × 10-7), and neurological involvement with DDX60L (rs62334264: OR = 4.12 [95% CI 2.34 to 7.24], p-value = 8.85 × 10-7). Our results emphasize the role of genetic factors in predisposing to specific clinical manifestations in Behçet's disease, and might shed additional light into disease heterogeneity, pathogenesis, and variability of Behçet's disease presentation across populations.

Heart-rate variability as a new marker for freezing predisposition in Parkinson's disease.

INTRODUCTION: Freezing of gait (FoG) is a debilitating symptom of advanced Parkinson's disease (PD) characterized by a sudden, episodic stepping arrest despite the intention to continue walking. The etiology of FoG is still unknown, but accumulating evidence unraveled physiological signatures of the autonomic nervous system (ANS) around FoG episodes. Here we aim to investigate for the first time whether detecting a predisposition for upcoming FoG events from ANS activity measured at rest is possible. METHODS: We recorded heart-rate for 1-min while standing in 28 persons with PD with FoG (PD + FoG), while OFF, and in 21 elderly controls (EC). Then, PD + FoG participants performed walking trials containing FoG-triggering events (e.g., turns). During these trials, n = 15 did experience FoG (PD + FoG+), while n = 13 did not (PD + FoG-). Most PD participants (n = 20: 10 PD + FoG+ and 10 PD + FoG-) repeated the experiment 2-3 weeks later, while ON, and none experienced FoG. We then analyzed heart-rate variability (HRV), i.e., the fluctuations in time intervals between adjacent heartbeats, mainly generated by brain-heart interactions. RESULTS: During OFF, HRV was significantly lower in PD + FoG + participants, reflecting imbalanced sympathetic/parasympathetic activity and disrupted self-regulatory capacity. PD + FoG- and EC participants showed comparable (higher) HRV. During ON, HRV did not differ among groups. HRV values did not correlate with age, PD duration, levodopa consumption, nor motor -symptoms severity scores. CONCLUSIONS: Overall, these results document for the first time a relation between HRV at rest and FoG presence/absence during gait trials, expanding previous evidence regarding the involvement of ANS in FoG.

Neurosurgical aspects of Noonan syndrome.

PURPOSE: Noonan syndrome (NS) is a rare neurodevelopmental syndrome characterized by dysmorphic features, congenital heart defects, neurodevelopmental delay, and bleeding diathesis. Though rare, several neurosurgical manifestations have been associated with NS, such as Chiari malformation (CM-I), syringomyelia, brain tumors, moyamoya, and craniosynostosis. We describe our experience in treating children with NS and various neurosurgical conditions, and review the current literature on neurosurgical aspects of NS. METHODS: Data were retrospectively collected from the medical records of children with NS who were operated at a tertiary pediatric neurosurgery department, between 2014 and 2021. Inclusion criteria were clinical or genetic diagnosis of NS, age < 18 years at treatment, and need for a neurosurgical intervention of any kind. RESULTS: Five cases fulfilled the inclusion criteria. Two had tumors, one underwent surgical resection. Three had CM-I, syringomyelia, and hydrocephalus, of whom one also had craniosynostosis. Comorbidities included pulmonary stenosis in two patients and hypertrophic cardiomyopathy in one. Three patients had bleeding diathesis, two of them with abnormal coagulation tests. Four patients were treated preoperatively with tranexamic acid, and two with Von Willebrand factor or platelets (1 each). One patient with a clinical bleeding predisposition developed hematomyelia following a syringe-subarachnoid shunt revision. CONCLUSIONS: NS is associated with a spectrum of central nervous system abnormalities, some of which with known etiology, while in others a pathophysiological mechanism has been suggested in the literature. When operating on a child with NS, a meticulous anesthetic, hematologic, and cardiac evaluation should be conducted. Neurosurgical interventions should then be planned accordingly.

Distinct pathophysiological characteristics in developing muscle from patients susceptible to malignant hyperthermia.

BACKGROUND: Most patients with malignant hyperthermia susceptibility diagnosed by the in vitro caffeine-halothane contracture test (CHCT) develop excessive force in response to halothane but not caffeine (halothane-hypersensitive). Hallmarks of halothane-hypersensitive patients include high incidence of musculoskeletal symptoms at rest and abnormal calcium events in muscle. By measuring sensitivity to halothane of myotubes and extending clinical observations and cell-level studies to a large group of patients, we reach new insights into the pathological mechanism of malignant hyperthermia susceptibility. METHODS: Patients with malignant hyperthermia susceptibility were classified into subgroups HH and HS (positive to halothane only and positive to both caffeine and halothane). The effects on [Ca2+]cyto of halothane concentrations between 0.5 and 3 % were measured in myotubes and compared with CHCT responses of muscle. A clinical index that summarises patient symptoms was determined for 67 patients, together with a calcium index summarising resting [Ca2+]cyto and spontaneous and electrically evoked Ca2+ events in their primary myotubes. RESULTS: Halothane-hypersensitive myotubes showed a higher response to halothane 0.5% than the caffeine-halothane hypersensitive myotubes (P<0.001), but a lower response to higher concentrations, comparable with that used in the CHCT (P=0.055). The HH group had a higher calcium index (P<0.001), but their clinical index was not significantly elevated vs the HS. Principal component analysis identified electrically evoked Ca2+ spikes and resting [Ca2+]cyto as the strongest variables for separation of subgroups. CONCLUSIONS: Enhanced sensitivity to depolarisation and to halothane appear to be the primary, mutually reinforcing and phenotype-defining defects of halothane-hypersensitive patients with malignant hyperthermia susceptibility.

Impact of local predisposing/precipitating factors and systemic drivers on peri-implant diseases.

BACKGROUND: Strong evidence suggests the infectious nature of peri-implant diseases occurring in susceptible hosts. Epidemiological reports, though, indicate that peri-implantitis is a site-specific entity. Hence, the significance of local factors that may predispose/precipitate plaque accumulation and the impact of systemic drivers that alter the immune response are relevant in the prevention and management of peri-implant disorders. PURPOSE: The purpose of the present review is to shed light on the significance of local and systemic factors on peri-implant diseases, making special emphasis on the associations with peri-implantitis. METHODS: The biologic plausibility and supporting evidence aiming at providing a concluding remark were explored in the recent scientific literature for local predisposing/precipitating factors and systemic drivers related to peri-implant diseases. RESULTS: Local predisposing factors such as soft tissue characteristics, implant position and prosthetic design proved being strongly associated with the occurrence of peri-implant diseases. Hard tissue characteristics, however, failed to demonstrate having a direct association with peri-implant diseases. Robust data points toward the strong link between residual sub-mucosal cement and peri-implant diseases, while limited data suggests the impact of residual sub-mucosal floss and peri-implantitis. Systemic drivers/habits such as hyperglycemia and smoking showed a strong negative impact on peri-implantitis. However, there is insufficient evidence to claim for any link between metabolic syndrome, atherosclerotic cardiovascular disease, and obesity and peri-implant diseases. CONCLUSION: Local predisposing/precipitating factors and systemic drivers may increase the risk of peri-implant diseases. Therefore, comprehensive anamnesis of the patients, educational/motivational programs and exhaustive prosthetically-driven treatment planning must be fostered aiming at reducing the rate of biological complications in implant dentistry.

Trauma center admission risk conditions and the probability for developing alcohol withdrawal syndrome: A retrospective study.

BACKGROUND: Because the proportion of trauma patients developing alcohol withdrawal syndrome (AWS) is low, AWS risk conditions have not been precisely delineated. We aimed to create multifactor screening strategies to assess probabilities for the likelihood of developing AWS. METHODS: We performed a retrospective chart review of 1,011 trauma patients admitted to a Level I trauma center to investigate the associations between AWS and probable AWS risk conditions. Included patients were adults who met trauma registry inclusion criteria and had blood alcohol concentration (BAC) testing performed. Patients were excluded if they had a traumatic brain injury with a Glasgow Coma Score (GCS) ≤ 8, or no BAC testing performed. We defined heavy drinking as daily drinking or >7 per week. RESULTS: AWS had univariate associations with heavy drinking history, Injury Severity Score (ISS) ≥15, psychiatric disorders, liver disease, smoking history, in-hospital bronchodilator administration, age ≥45, male sex, Intensive Care Unit (ICU) admission, serum aspartate aminotransferase (AST) ≥40 U/L, and cognitive preservation (GCS ≥13 with BAC ≥100 mg/dL) (all, p < 0.05). ICU admission, AST ≥40 U/L, cognitive preservation, male sex, and age ≥45 had associations with ISS ≥15 or alcohol misuse (all, p < 0.0001). For patients with age ≥45 and heavy drinking history or age <45 and heavy drinking history with ISS ≥15 and ICU admission, the AWS proportion (15.3%) was greater in comparison to other patients (0.3%). The AWS risk score was the sum of the following nine conditions, assigned a zero when the condition was absent and one when present (range 0-9): ISS ≥15, psychiatric disorders, liver disease, smoking history, in-hospital bronchodilator administration, age ≥45, male sex, AST ≥40 U/L, and cognitive preservation. The AWS proportion was greater with a risk score of 5-9 (16.8%) than of 0-4 (1.2%; p < 0.0001). CONCLUSIONS: AWS in the setting of traumatic injury is associated with multiple risk conditions. The presence of multiple risk conditions might have additive effects that could contribute toward a clinical manifestation of AWS. The identified risk conditions may be associated with a hyperadrenergic state.

Lupus anticoagulant-hypoprothrombinemia syndrome with severe bleeding diathesis after coronavirus disease 2019: a case report.

Acquired antibodies against factor II (prothrombin) are rare and most commonly associated with severe liver disease or vitamin K antagonist treatment. In very rare cases, these antibodies and associated hypoprothrombinemia are found in patients with lupus anticoagulant (LAC), an antiphospholipid antibody that inhibits phospholipid-dependent coagulation tests. This uncommon entity, called lupus anticoagulant-hypoprothrombinemia syndrome (LAHPS), may cause both severe, life-threatening bleeding and a predisposition to thrombosis. Coronavirus disease 2019 (COVID-19) is associated with a variety of coagulation abnormalities and an increased risk of thrombosis. Bleeding may occur, but it is less common than thromboembolism and has mostly been described in association with the severity of the disease and anticoagulation treatment in hospitalized patients, rarely in the post-acute phase of the disease. We report on a case of an 80-year-old man who developed LAHPS with prothrombin antibodies and severe bleeding after COVID-19.

Reducing infection risk in multiple sclerosis and neuromyelitis optica spectrum disorders: a Brazilian reference center's approach.

BACKGROUND: Multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD) are the most common autoimmune diseases of the central nervous system (CNS). They present chronic relapsing courses that demand treatment with disease-modifying drugs (DMDs) to prevent inflammatory activity. Disease-modifying drugs lead to immunomodulation or immunosuppression through diverse mechanisms (e.g., shifting lymphocyte and cytokine profile, suppressing specific lymphocyte subpopulations). Thus, patients are more prone to infectious complications and associated worsening of disease. OBJECTIVE: To present feasible strategies for mitigating the infection risk of MS and NMOSD treated patients. METHODS: Targeted literature review concerning the management of infection risk with an emphasis on vaccination, therapy-specific measures, and particularities of the Brazilian endemic infectious diseases' scenario. CONCLUSION: We propose a vaccination schedule, infectious screening routine, and prophylactic measures based on the current scientific evidence. Awareness of emergent tropical diseases is necessary due to evidence of demyelinating events and possible parainfectious cases of MS and NMOSD.

ANTECEDENTES: A esclerose múltipla (EM) e a doença do espectro neuromielite optica (NMOSD) são as doenças autoimunes mais comuns do sistema nervoso central (SNC). Ambas apresentam curso crônico com recaídas (surtos) e exigem tratamento com drogas modificadoras de doenças (DMDs) para a prevenção de atividade inflamatória. As DMDs levam à imunomodulação ou imunossupressão através de diversos mecanismos (por exemplo deslocando e/ou suprimindo subpopulações linfocitárias ou alterando perfil de produção de citocinas). Desta forma, os pacientes com EM ou NMOSD são mais propensos a complicações infecciosas, as quais podem levar ao agravamento de suas doenças de base. OBJETIVO: Apresentar estratégias viáveis para mitigar o risco de infecção de pacientes com EM ou NMOSD sob tratamento. MéTODOS: Revisão bibliográfica focada em manejo de risco de infecção com ênfase em vacinação, medidas específicas de tratamento e particularidades de doenças infecciosas endêmicas do Brasil. CONCLUSãO: Propomos um calendário de vacinação, rotina de triagem infecciosa e medidas profiláticas baseadas em evidências científicas atuais. A conscientização das doenças tropicais emergentes é necessária devido a evidências de eventos desmielinizantes e possíveis casos parainfecciosos de EM e NMOSD.

Management of patients susceptible to malignant hyperthermia: A surgeon's perspective.

OBJECTIVES: Malignant hyperthermia (MH) susceptibility caries broad implications for the care of pediatric surgical patients. While precautions must often be taken for only a vague family history, two options exist to assess MH-susceptibility. We evaluate the use of MH precautions and susceptibility testing at a freestanding children's hospital. METHODS: This single institution retrospective cohort study identified patients of any age who received general anesthetics utilizing MH precautions over a five-year period. The electronic medical record was further queried for patients diagnosed with MH. The indication for MH precautions and uses of susceptibility testing are assessed. Secondary outcomes included a diagnosis of bona fide MH. RESULTS: A total of 125 patients received 174 anesthetics with MH precautions at a mean age of 114 months (0-363 months). Otolaryngology was the procedural service most frequently involved in the care of the cohort (n = 45; 26%). A reported personal or family history of MH (n = 102; 59%) was the most common indication for precautions, followed by muscular dystrophy (n = 29; 17%). No MH events occurred in the cohort and further review of ICD-9 and -10 diagnosis codes found no MH diagnoses. No study subjects received muscle biopsy and contracture testing and only 5 (4%) underwent genetic testing for genomic variants known to cause MH susceptibility. A case example is given to highlight the implications of a reported MH history. CONCLUSION: Otolaryngologists should maintain a familiarity with the precautions necessary to manage patients at risk for MH and MH-like reactions. Without an accessible test to rule out susceptibility, surgeons must rely on a careful history to appropriately utilize precautions. An inappropriate label of "MH-susceptible" may result in decreased access to care and treatment delays.

[Immune-mediated thrombotic thrombocytopenic purpura and susceptible HLA alleles].

Thrombotic thrombocytopenic purpura (TTP) is an extremely rare and fatal thrombotic disorder characterized by impaired enzyme activity of von Willebrand factor cleaving protease, also known as ADAMTS13. Immune-mediated TTP (iTTP) is an acquired form of TTP caused by the production of auto-antibodies against ADAMTS13. The pathophysiology of autoimmune disorders is multifactorial, with several human leukocyte antigen (HLA) alleles identified as a genetic risk factor for autoimmune diseases known as susceptible HLA. In the early 2010s, three distinct European groups revealed that DRB1*11 is one of the most susceptible alleles in acquiring iTTP among Caucasians based on HLA typing data. Several in silico predictions for allele-restricted ADAMTS13 epitopes against T cells are made in this context, followed by an in vitro validation employing mass spectrometry using eluted peptides and T-cell assays. However, similar analyses in a genetically distinct Japanese population have not yet been conducted. We used next-generation sequencing to perform HLA typing for 52 Japanese patients with iTTP from 19 institutes. Our detailed analysis revealed that the specific allele DRB1*08:03 was identified as a genetic risk factor for iTTP in Japanese patients, but there were no statistically significant differences in the allele frequency of DRB1*11 between iTTP and healthy controls.

Allogeneic blood transfusions and infection risk in lumbar spine surgery: An American College of Surgeons National Surgery Quality Improvement Program Study.

BACKGROUND: Allogenic blood transfusions can lead to immunomodulation. Our purpose was to investigate whether perioperative transfusions were associated with postoperative infections and any other adverse events (AEs), after adjusting for potential confounding factors, following common elective lumbar spinal surgery procedures. STUDY DESIGN AND METHODS: We performed a multivariate, propensity-score matched, regression-adjusted retrospective analysis of the American College of Surgeons National Surgical Quality Improvement Program database between 2012 and 2016. All lumbar spinal surgery procedures were identified (n = 174,891). A transfusion group (perioperative transfusion within 72 h before, during, or after principal surgery; n = 1992) and a control group (no transfusion; n = 1992) were formed. Following adjustment for between-group baseline features, adjusted odds ratios (aOR) and 95% confidence intervals (95% CI) were calculated using a multivariate logistic regression model for any surgical site infection (SSI), superficial SSI, deep SSI, wound dehiscence, pneumonia, urinary tract infection, sepsis, any infection, mortality, and any AEs. RESULTS: Transfusion was associated with an increased risk of each specific infection, mortality, and any AEs. Statistically significant between-group differences were demonstrated with respect to any SSI (aOR: 1.48; 95% CI: 1.01-2.16), deep SSI (aOR: 1.66; 95% CI: 0.98-2.85), sepsis (aOR: 2.69; 95% CI: 1.43-5.03), wound dehiscence (aOR: 2.27; 95% CI: 0.86-6.01), any infection (aOR: 1.46; 95% CI: 1.13-1.88), any AEs (aOR: 1.80; 95% CI: 1.48-2.18), and mortality (aOR: 2.17; 95% CI: 0.77-6.36). CONCLUSION: We showed an association between transfusion and infection in lumbar spine surgery after adjustment for various applicable covariates. Sepsis had the highest association with transfusion. Our results reinforce a growing trend toward minimizing perioperative transfusions, which may lead to reduced infections following lumbar spine surgery.

Relationship between allergic transfusion reactions and allergic predisposition among pediatric patients with hematological/oncological disease.

BACKGROUND: Allergic transfusion reactions (ATRs) manifest frequently as transfusion reactions, and their onset may be related to a patient's allergic predisposition. Moreover, although pediatric patients with hematological/oncological disease are more susceptible to ATRs, the relationship between allergic predisposition and ATRs remains to be fully clarified. STUDY DESIGN AND METHODS: Patients who were diagnosed with pediatric hematological/oncological disease and received transfusion at the study institutions were included. We determined patient background information related to their allergy history, measured the levels of allergen-specific immunoglobulin E (IgE) using sera obtained on diagnosis, and analyzed their associations with ATR onset. RESULTS: Of the 363 patients analyzed, 144 developed ATRs. Multivariate analysis identified cases with high basophils in the peripheral blood, and Dermatophagoides pteronyssinus- and egg white-specific IgEs were involved in the development of ATR in all age groups. Meanwhile, a history of food allergies, and positivity for Japanese cypress- and D. pteronyssinus-specific IgEs were risk factors for developing ATRs in the <5 years age group. Moreover, patients aged 5-<10 years with a history of asthma, allergic rhinitis, pollinosis, or atopic dermatitis, and those aged ≥10 years with positivity for dog dander-specific IgE were at risk for developing ATRs. CONCLUSION: The allergic constitution of patients plays a role in ATR onset even in pediatric hematological/oncological diseases. Therefore, advance confirmation of a patient's allergic constitution may partly predict the onset of ATRs. However, since multiple allergic predispositions within complex mechanisms may be involved in the onset of ATRs, further verification is required.

Genome-wide association analyses identify new Brugada syndrome risk loci and highlight a new mechanism of sodium channel regulation in disease susceptibility.

Brugada syndrome (BrS) is a cardiac arrhythmia disorder associated with sudden death in young adults. With the exception of SCN5A, encoding the cardiac sodium channel NaV1.5, susceptibility genes remain largely unknown. Here we performed a genome-wide association meta-analysis comprising 2,820 unrelated cases with BrS and 10,001 controls, and identified 21 association signals at 12 loci (10 new). Single nucleotide polymorphism (SNP)-heritability estimates indicate a strong polygenic influence. Polygenic risk score analyses based on the 21 susceptibility variants demonstrate varying cumulative contribution of common risk alleles among different patient subgroups, as well as genetic associations with cardiac electrical traits and disorders in the general population. The predominance of cardiac transcription factor loci indicates that transcriptional regulation is a key feature of BrS pathogenesis. Furthermore, functional studies conducted on MAPRE2, encoding the microtubule plus-end binding protein EB2, point to microtubule-related trafficking effects on NaV1.5 expression as a new underlying molecular mechanism. Taken together, these findings broaden our understanding of the genetic architecture of BrS and provide new insights into its molecular underpinnings.

Delirium in trauma patients: a 1-year prospective cohort study of 2026 patients.

BACKGROUND: Delirium in trauma surgery is common, especially post-operatively, but medical characteristics, risk factors and residence post-discharge have not comprehensively been investigated in all trauma patients. METHODS: Over 1 year, 2026 trauma patients were prospectively screened for delirium with the following tools: Delirium Observation screening scale (DOS), Intensive Care Delirium Screening Checklist (ICDSC) and a DSM (Diagnostic and Statistical Manual)-5, nursing tool (ePA-AC) construct. Risk factors-predisposing und precipitating-for delirium were assessed via multiple regression analysis. RESULTS: Of 2026 trauma patients, 440 (21.7%) developed delirium, which was associated with an increased risk of assisted living (OR 6.42, CI 3.92-10.49), transfer to nursing home (OR 4.66, CI 3.29-6.6), rehabilitation (OR 3.96, CI 3.1-5.1), or death (OR 70.72, CI 22-227.64). Intensive care management (OR 18.62, CI 14.04-24.68), requirement of ventilation (OR 32.21, CI 21.27-48.78), or its duration (OR 67.22, CI 33.8-133.71) all increased the risk for developing delirium. Relevant predisposing risk factors were dementia (OR 50.92, CI 15.12-171.45), cardiac insufficiency (OR 11.76, CI 3.6-38.36), and polypharmacy (OR 5.9, CI 4.01-8.68).Relevant precipitating risk factors were brain edema (OR 40.53, CI 4.81-341.31), pneumonia (OR 39.66, CI 8.89-176.93) and cerebral inflammation (OR 21.74, CI 2.34-202.07). CONCLUSION: Delirium in trauma patients is associated with poor outcome as well as with intensive care management and various predisposing and/or precipitating factors. Three quarters of patients who had undergone delirium were not able to live independently at home any more.

Susceptibilidad antimicrobiana de bacterias aisladas en sepsis del acceso vascular. Instituto de Nefrología, 2019 / Antimicrobial susceptibility of bacteria isolated from vascular access sepsis. Institute of Nephrology, 2019

Introducción: El acceso vascular en hemodiálisis es esencial para el enfermo renal por su repercusión en la calidad de vida. La fístula arteriovenosa, los catéteres para hemodiálisis o las prótesis vasculares, aunque han evolucionado gradualmente hacia el perfeccionamiento, son proclives a las infecciones debidas fundamentalmente a bacterias de la microbiota de la piel y mucosas. Objetivo: Caracterizar la susceptibilidad antimicrobiana de las bacterias aisladas de pacientes con sepsis del acceso vascular en el servicio de hemodiálisis del Instituto de Nefrología. Material y Métodos: Estudio de corte transversal, en el período comprendido entre enero a diciembre de 2019. El universo estuvo constituido por 112 aislamientos obtenidos a partir de muestras de hemocultivos, secreciones y puntas de catéter de los pacientes con bacteriemias, sepsis o secreción en el sitio de inserción del catéter o acceso vascular. Resultados: El 72,3 por ciento de las muestras estudiadas fueron hemocultivos. Se obtuvo 38,3 % de aislamientos de Staphylococcus aureus, sensibles en su totalidad a la vancomicina. El 68,1 % de las cepas de Escherichia coli fueron productoras de betalactamasas de espectro extendido (BLEE) con sensibilidad superior a 60 % a aminoglucósidos y carbapenémicos; similar patrón de sensibilidad mostraron las cepas de Pseudomonas, no obstante, el 100% fue resistente a las cefalosporinas. Conclusiones: No se reportó resistencia a la vancomicina en el estudio. Los aislamientos de los gérmenes gramnegativos mostraron elevada resistencia a las cefalosporinas y una buena sensibilidad a aminoglucósidos y carbapenémicos(AU)

Introduction: The vascular access in hemodialysis is essential for the renal patient both for its associated morbidity and mortality as well as for its impact on quality of life. Although arteriovenous fistula, hemodialysis catheters or vascular prostheses have gradually evolved toward improvement, they are prone to infections primarily due to bacteria on the skin and mucosal microbiota. Objective: To characterize the antimicrobial susceptibility of bacteria isolated from patients with vascular access sepsis in the hemodialysis service of the Institute of Nephrology. Material and Methods: A cross-sectional study was conducted in the period January-December 2019. The universe consisted of all 112 isolates obtained from blood culture samples, secretions and catheter tips from patients with bacteremia, sepsis or discharge at the site of catheter insertion or vascular access. Results: The results show that 72.3% of the samples studied were blood cultures. Also, 38.3 percent of Staphylococcus aureus isolates, which were totally sensitive to vancomycin, were obtained. On the other hand, 68.1% of Escherichia coli strains were extended spectrum beta-lactamases (ESBL) producers with sensitivity to aminoglycosides and carbapenems greater than 60%. Pseudomonas strains exhibited a similar pattern of sensitivity, however, 100% were resistant to cephalosporins. Conclusions: No resistance to vancomycin was reported in this study. Gram-negative isolates showed high resistance to cephalosporins and good sensitivity to aminoglycosides and carbapenems(AU)

Adipose tissue is a critical regulator of osteoarthritis.

Osteoarthritis (OA), the leading cause of pain and disability worldwide, disproportionally affects individuals with obesity. The mechanisms by which obesity leads to the onset and progression of OA are unclear due to the complex interactions among the metabolic, biomechanical, and inflammatory factors that accompany increased adiposity. We used a murine preclinical model of lipodystrophy (LD) to examine the direct contribution of adipose tissue to OA. Knee joints of LD mice were protected from spontaneous or posttraumatic OA, on either a chow or high-fat diet, despite similar body weight and the presence of systemic inflammation. These findings indicate that adipose tissue itself plays a critical role in the pathophysiology of OA. Susceptibility to posttraumatic OA was reintroduced into LD mice using implantation of a small adipose tissue depot derived from wild-type animals or mouse embryonic fibroblasts that undergo spontaneous adipogenesis, implicating paracrine signaling from fat, rather than body weight, as a mediator of joint degeneration.

Could targeting immunometabolism be a way to control the burden of COVID-19 infection?

This review portrays the metabolic consequences of Covid-19 infection at different stages of the clinical syndrome. It also describes how events can change when patients with metabolic problems are infected and the effects that diet and nutrition might play to influence the outcome of infection. We also discuss the types of maneuvers that could be used to reshape metabolic events and question if this approach could be a practical therapy used alone or in combination with other approaches to reduce the burden of Covid-19 infection.