Predictors of transition to schizophrenia and other long-lasting non-affective psychoses in first-episode patients with acute and transient psychotic disorders: A validation study

Background and objectives Almost half of the individuals with a first-episode of psychosis who initially meet criteria for acute and transient psychotic disorder (ATPD) will have had a diagnostic revision during their follow-up, mostly toward schizophrenia. This study aimed to determine the proportion of diagnostic transitions to schizophrenia and other long-lasting non-affective psychoses in patients with first-episode ATPD, and to examine the validity of the existing predictors for diagnostic shift in this population. Methods We designed a prospective two-year follow-up study for subjects with first-episode ATPD. A multivariate logistic regression analysis was performed to identify independent variables associated with diagnostic transition to persistent non-affective psychoses. This prediction model was built by selecting variables on the basis of clinical knowledge. Results Sixty-eight patients with a first-episode ATPD completed the study and a diagnostic revision was necessary in 30 subjects at the end of follow-up, of whom 46.7% transited to long-lasting non-affective psychotic disorders. Poor premorbid adjustment and the presence of schizophreniform symptoms at onset of psychosis were the only variables independently significantly associated with diagnostic transition to persistent non-affective psychoses. Conclusion Our findings would enable early identification of those inidividuals with ATPD at most risk for developing long-lasting non-affective psychotic disorders, and who therefore should be targeted for intensive preventive interventions. (AU)

The Prevalence of the Nasal Vestibular Body in Patients With Nasal Obstruction.

Background and aim Nasal obstruction is one of the most common reasons for consultation addressed by otolaryngologists. There are anatomical, physiological, and pathological etiologies. Sometimes the treatment can become a challenge for the specialist, so a detailed evaluation of the etiologies must be carried out. The involvement of the nasal vestibular body (NVB) in obstructive symptoms has been described. Therefore, we must be familiar with its anatomy, presentation, and contribution to this symptomatology. This study aimed to highlight the importance of NVB in the role of nasal obstruction and know the impact that it adds to the symptoms of patients through a validated instrument on their quality of life. Material and methods A retrospective, descriptive, and analytical study was conducted on 113 patients with nasal obstruction who attended the outpatient clinic of the Otolaryngology and Head and Neck Surgery Service in a tertiary-level hospital in Monterrey, Mexico from January 2021 to January 2023. The Nasal Obstruction Symptom Evaluation (NOSE) scale was applied to assess the impact of this symptom on the quality of life of the subjects. The causes involved in the obstructive symptoms were identified by physical examination, including NVB. Two groups were made as follows: with the presence of the NVB and with the absence of the NVB, and the means of the NOSE scale were compared. Results A total of 113 patients were included, 59 male patients (52.20%) and 54 female patients (47.80%). The presence of NBV was found in 72 patients (63.70%). Other causes of nasal obstruction were found in 35 patients (31%), with chronic rhinitis being the most frequent in 27 subjects (23.90%). The mean NOSE scale score was higher in the group with the presence of the NVB than in the group with the absence of the NVB (p<0.05). The primary outcome of this study was to know the prevalence of NVB in the Hispanic population with nasal obstruction who attends the otolaryngology clinic. The secondary outcome was to know the relationship between the presence of NVB and the NOSE scores. Conclusion In this study, we observed that NVB is frequently present in patients with nasal obstruction in northeastern Mexico. There is an association between the presence of NVB and higher scores on the NOSE scale. New research will be needed to assess the effectiveness of NVB surgery in improving nasal obstruction and to determine the impact of NVB on nasal obstruction in isolation.

Prognostic value of systemic immune-inflammation index and serological biomarkers for deep neck infections / Valor pronóstico del índice de inmunoinflamación sistémica y biomarcadores serológicos para infecciones profundas del cuello

Background: Inflammatory biomarkers, including C-reactive protein, erythrocyte sedimentation rate, neutrophil tolymphocyte ratio, platelet to lymphocyte ratio, and the systemic immune-inflammation index, have been proposedas prognostic factors diverse pathologies. However, their application for deep neck infections has yet to be clarified.Material and Methods: We performed a retrospective study of 163 adult patients with diagnosis of deep neck infec-tions with the aim to evaluate the association between serological biomarkers with complications and outcomes ofpatients with DNI. Studied variables included demographic data, complications of DNI, outcomes, complicationsand death of the included subjects. The evaluated serological biomarkers were hemoglobin, leukocytes, neutrophils,lymphocytes, platelets, glucose, creatinine, albumin, CRP, and ESR. NLR, PLR, and SIII index were estimated.Results: The patients’ mean age was 40.6 ± 15.3 years. Complications of DNI were observed in 19.6% (n=32) patients, being the need for tracheostomy due to airway obstruction (11%, n=18) and mediastinitis (8.6%, n= 14) themost common. Evaluated subjects had an increased value of serological biomarkers (SII index 2639.9 ± 2062.9,NLR 11.3 ± 8.5, PLR 184.1 ± 108.5, CRP 12.6 ± 8.9 mg/dL, ESR 20.7 ± 9.1 mm/h). Patients with complicationshad a significantly higher value of all inflammatory parameters (p < 0.05). A SII index cut-off value of 2975 wasselected from a ROC curve analysis. A sensitivity of 93.8%, specificity of 86.3%, a positive predictive value of62.5%, and a negative predictive value of 98.3% are reported. The SII index was found to have an increased positive predictive value compared to NLR, PLR, and CRP for DNI complications.Conclusions: Our analysis concluded that the SII index, NLR, and PLR are valuable biomarkers to assess the risk value of 2975.(AU)

Initial evaluation and external validation of 68Ga-PSMA-11 PET/CT in tubarial gland characterization.

INTRODUCTION: Radiotracer 68Ga-PSMA-11 used in PET/CT scans allows for identification and localization of gland tissue. It allows for their consideration in clinical scenarios and to design further and stronger research to answer pertinent questions regarding their function and implications. We aimed to externally validate first reported findings of location, size, and ligand uptake of the tubarial glands using 68Ga-PSMA-11 PET/CT. MATERIALS AND METHODS: A cross-sectional study was performed with 68Ga-PSMA-11 PET/CT studies of patients with prostate cancer confirmed diagnosis from the database of the Radiology Department from 2018 to 2022. The maximum cephalocaudal length (CCL) in the tubarial glands and the Maximum Standardized Uptake Value (SUVmax) of major glands were recorded. RESULTS: A total of 202 patients were included (mean age 67.43 ± 8.5). The mean CCL of the tubarial glands was 37.38 ± 9.84 and a SUVmax of 6.56 ± 2.14. The rest of the glands were as follows: parotid 15.12 ± 4.43, submandibular 16.82 ± 5.43 and sublingual 5.84 ± 3.24. No differences were found between laterality. A weak correlation between age and SUVmax of tubarial glands was identified. Tubarial glands had a similar 68Ga-PSMA-11 uptake to that of sublingual glands. CONCLUSION: This study corroborates the existence of a conglomerate of glands in the nasopharynx roof, near the posterolateral pharyngeal recess. It serves as validation in a different population with similar results in previous research. Without 68GA-PSMA-11 PET/CT the abundance, configuration and potential clinical relevance of these glands would probably not have been identified. Radiotracer uptake was similar amongst the major salivary glands, with a more similar uptake to that shown by the sublingual gland.

Insularity determines nestling sex ratio variation in Egyptian vulture populations.

Variation in offspring sex ratio, particularly in birds, has been frequently studied over the last century, although seldom using long-term monitoring data. In raptors, the cost of raising males and females is not equal, and several variables have been found to have significant effects on sex ratio, including food availability, parental age, and hatching order. Sex ratio differences between island populations and their mainland counterparts have been poorly documented, despite broad scientific literature on the island syndrome reporting substantial differences in population demography and ecology. Here, we assessed individual and environmental factors potentially affecting the secondary sex ratio of the long-lived Egyptian vulture Neophron percnopterus. We used data collected from Spanish mainland and island populations over a ca. 30-year period (1995-2021) to assess the effects of insularity, parental age, breeding phenology, brood size, hatching order, type of breeding unit (pairs vs. trios), and spatial and temporal variability on offspring sex ratio. No sex bias was found at the population level, but two opposite trends were observed between mainland and island populations consistent with the island syndrome. Offspring sex ratio was nonsignificantly female-biased in mainland Spain (0.47, n = 1112) but significantly male-biased in the Canary Islands (0.55, n = 499), where a male-biased mortality among immatures could be compensating for offspring biases and maintaining a paired adult sex ratio. Temporal and spatial variation in food availability might also have some influence on sex ratio, although the difficulties in quantifying them preclude us from determining the magnitude of such influence. This study shows that insularity influences the offspring sex ratio of the Egyptian vulture through several processes that can affect island and mainland populations differentially. Our research contributes to improving our understanding of sex allocation theory by investigating whether sex ratio deviations from parity are possible as a response to changing environments comprised by multiple and complexly interrelated factors.

Pembrolizumab as first-line treatment for advanced NSCLC in older adults: A phase II clinical trial evaluating geriatric and quality-of-life outcomes.

OBJECTIVES: Since specific data on immunotherapy in older adults with advanced non-small cell lung cancer (aNSCLC) are scarce, we designed this study to determine the overall survival (OS) at one year of first-line pembrolizumab in patients older than 70 years with aNSCLC expressing PD-L1. Secondary objectives included progression-free survival, disease-specific survival, response rate, tolerability, quality of life (QoL) changes, and geriatric assessments. MATERIALS AND METHODS: A single-arm, open-label, phase II clinical trial was carried out by the Spanish Lung Cancer Group between February 2018 and November 2019 at ten active sites in Spain. We included patients 70 years old and older with histological or cytological documented stage IIIB or IV aNSCLC and PD-L1 expression ≥ 1%. Each subject received 200 mg of intravenous pembrolizumab every three weeks for a maximum of two years. RESULTS: 83 patients were recruited for the study and 74 were finally analysed. Most were male (N = 64, 86.5%) and former smokers (N = 51, 68.9%). 24 patients (32.4%) completed at least one year of treatment, 62 (83.7%) discontinued treatment, and 30 (40.5%) experienced disease progression. The median follow-up of our cohort was 18.0 months [range: 0.1-47.7] and 46 patients (62.2%) died during the period of study. The estimated OS at one year was 61.7% (95% CI: 49.6-71.8%) and the median OS of our cohort was 19.2 months (95% CI: 11.3-25.5). QoL tended to improve throughout the study, although the differences were not statistically significant. The main geriatric scores remained stable, except for a worsening in nutritional status (P = 0.004) and an improvement in frailty (P = 0.028). CONCLUSION: Our results support treating older adults with aNSCLC expressing PD-L1 with pembrolizumab in monotherapy. The stability of most geriatric scores and the positive trend on the patients' QoL should be highlighted, although our results did not reach statistical significance.

Neurovascular structures in the lateral recess of the sphenoid sinus. A computed tomography evaluation / Estructuras neurovasculares en el receso lateral del seno esfenoidal mediante tomografía computarizada

Introduction and objectives Anatomical variations of the lateral recess of the sphenoid sinus and its relations with the adjacent neurovascular structures should be preoperatively evaluated to plan an adequate surgical approach and avoid iatrogenic injuries. This study aims to analyze the patterns of pneumatization of the lateral recess of the sphenoid sinus and their association with the presence of protrusion and dehiscence of the optic canal, carotid canal, vidian canal, and maxillary nerve. Materials and methods A retrospective evaluation of 320 sphenoid sinuses by computed tomography was performed. Studied variables included type of lateral recess, and protrusion, and dehiscence of the optic and carotid canal, and vidian and maxillary nerve. Results The mean age was 45.67±17.43. A total of 55.6% (n=178) of the evaluated sphenoid sinuses corresponded to male subjects. Protrusion of the carotid canal, maxillary nerve, and vidian canal was associated with a type 3 lateral recess pneumatization, while dehiscence of these structures was most commonly observed in a type 2 lateral recess (p=<0.001). Conclusions Protrusion or dehiscence of neurovascular structures surrounding the sphenoid sinus has been associated with the extent of pneumatization of the lateral recess, increasing the risk of intraoperative injury. Preoperative identification of anatomical variations is mandatory to select the best approach for skull base lesions and avoid iatrogenic injuries (AU)

Introducción y objetivos Las variaciones anatómicas del receso lateral del seno esfenoidal, y su relación con las estructuras neurovasculares adyacentes deben ser evaluados de manera preoperatoria para planear un abordaje quirúrgico adecuado, y evitar lesiones iatrogénicas. El objetivo del presente estudio es analizar los patrones de neumatización del receso lateral del seno esfenoidal y su asociación con la presencia de protrusión y dehiscencia del canal óptico, canal carotídeo, canal vidiano y del nervio maxilar. Material y métodos Se realizó una evaluación retrospectiva de 320 senos esfenoidales por tomografía computarizada. Las variables estudiadas fueron el tipo de receso lateral y la protrusión y dehiscencia del canal óptico, canal carotídeo, canal vidiano y del nervio maxilar. Resultados La edad media de los pacientes fue de 45,67±17,43 años. Un total del 55,6% (n=178) de los senos esfenoidales evaluados correspondieron a pacientes del sexo masculino. La protrusión del canal carotídeo, nervio maxilar y canal vidiano se asoció a la neumatización de receso lateral tipo 3, mientras que la dehiscencia de estas mismas estructuras observó más frecuentemente en patrón de neumatización de receso lateral tipo 2 (p≤0,001). Conclusión La protrusión o dehiscencia de estructuras neurovasculares adyacentes al seno esfenoidal se han asociado con la extensión de la neumatización del receso lateral, aumentando el riesgo de lesiones intraoperatorias. La identificación preoperatoria de variantes anatómicas es crucial para seleccionar el mejor abordaje quirúrgico para lesiones de base de cráneo y evitar lesiones iatrogénicas (AU)

Reduction in hippocampal GABAergic transmission in a low birth weight rat model of depression.

Prenatal stress is believed to increase the risk of developing neuropsychiatric disorders, including major depression. Adverse genetic and environmental impacts during early development, such as glucocorticoid hyper-exposure, can lead to changes in the foetal brain, linked to mental illnesses developed in later life. Dysfunction in the GABAergic inhibitory system is associated with depressive disorders. However, the pathophysiology of GABAergic signalling is poorly understood in mood disorders. Here, we investigated GABAergic neurotransmission in the low birth weight (LBW) rat model of depression. Pregnant rats, exposed to dexamethasone, a synthetic glucocorticoid, during the last week of gestation, yielded LBW offspring showing anxiety- and depressive-like behaviour in adulthood. Patch-clamp recordings from dentate gyrus granule cells in brain slices were used to examine phasic and tonic GABAA receptor-mediated currents. The transcriptional levels of selected genes associated with synaptic vesicle proteins and GABAergic neurotransmission were investigated. The frequency of spontaneous inhibitory postsynaptic currents (sIPSC) was similar in control and LBW rats. Using a paired-pulse protocol to stimulate GABAergic fibres impinging onto granule cells, we found indications of decreased probability of GABA release in LBW rats. However, tonic GABAergic currents and miniature IPSCs, reflecting quantal vesicle release, appeared normal. Additionally, we found elevated expression levels of two presynaptic proteins, Snap-25 and Scamp2, components of the vesicle release machinery. The results suggest that altered GABA release may be an essential feature in the depressive-like phenotype of LBW rats.

Corrigendum: Translating the observed differences in interleukin-6 levels between some antiretroviral regimens into potential long-term risk of serious non-AIDS events: A modeling study.

[This corrects the article DOI: 10.3389/fimmu.2022.976564.].

Gold Nanoparticles as Drug Carriers: The Role of Silica and PEG as Surface Coatings in Optimizing Drug Loading.

The use of gold nanoparticles as drug delivery systems has received increasing attention due to their unique properties, such as their high stability and biocompatibility. However, gold nanoparticles have a high affinity for proteins, which can result in their rapid clearance from the body and limited drug loading capabilities. To address these limitations, we coated the gold nanoparticles with silica and PEG, which are known to improve the stability of nanoparticles. The synthesis of the nanoparticles was carried out using a reduction method. The nanoparticles' size, morphology, and drug loading capacity were also studied. The SEM images showed a spherical and homogeneous morphology; they also showed that the coatings increased the average size of the nanoparticles. The results of this study provide insight into the potential of gold nanoparticles coated with silica and PEG as drug delivery systems. We used ibuprofen as a model drug and found that the highest drug load occurred in PEG-coated nanoparticles and then in silica-coated nanoparticles, while the uncoated nanoparticles had a lower drug loading capacity. The coatings were found to significantly improve the stability and drug load properties of the nanoparticles, making them promising candidates for further development as targeted and controlled release drug delivery systems.

Neurovascular structures in the lateral recess of the sphenoid sinus. A computed tomography evaluation.

INTRODUCTION AND OBJECTIVES: Anatomical variations of the lateral recess of the sphenoid sinus and its relations with the adjacent neurovascular structures should be preoperatively evaluated to plan an adequate surgical approach and avoid iatrogenic injuries. This study aims to analyze the patterns of pneumatization of the lateral recess of the sphenoid sinus and their association with the presence of protrusion and dehiscence of the optic canal, carotid canal, vidian canal, and maxillary nerve. MATERIALS AND METHODS: A retrospective evaluation of 320 sphenoid sinuses by computed tomography was performed. Studied variables included type of lateral recess, and protrusion, and dehiscence of the optic and carotid canal, and vidian and maxillary nerve. RESULTS: The mean age was 45.67±17.43. A total of 55.6% (n=178) of the evaluated sphenoid sinuses corresponded to male subjects. Protrusion of the carotid canal, maxillary nerve, and vidian canal was associated with a type 3 lateral recess pneumatization, while dehiscence of these structures was most commonly observed in a type 2 lateral recess (p=<0.001). CONCLUSIONS: Protrusion or dehiscence of neurovascular structures surrounding the sphenoid sinus has been associated with the extent of pneumatization of the lateral recess, increasing the risk of intraoperative injury. Preoperative identification of anatomical variations is mandatory to select the best approach for skull base lesions and avoid iatrogenic injuries.

Early maladaptive schemas as a risk factor for fibromyalgia: A case-control study.

OBJECTIVE: There is evidence supporting the relationship between early stress and childhood trauma and the development of fibromyalgia (FM). Early maladaptive schemas (EMSs) are considered a consequence of early stress. Previous research has shown their role in maintaining stress responses and their relevance in other populations with pain. The main aim of this study has been to analyze the presence of EMSs in patients with FM compared to healthy adult women. In addition, the relationship between the strength of EMSs and pain intensity was tested. METHOD: The total sample consisted of 167 women: 83 patients with FM and 84 healthy controls. RESULTS: Chi-square analyses showed that the percentage of participants with clinically significant scores is higher for patients with FM in 11 of the 18 EMSs evaluated. Moreover, discriminant analyses revealed that these EMS are useful to discriminate between FM and healthy controls, classifying 74.2% of original cases. In relation to the second aim, the mean pain intensity correlated with the strength of several EMSs: approval seeking, unrelenting standards, insufficient self-control, and mistrust/abuse. CONCLUSIONS: The current study highlights that a high rate of patients with FM have clinically significant EMSs compared to healthy matched controls, as has been found in other populations with pain. Besides, this study provides initial evidence that EMSs are positively associated with the pain experienced by patients with FM, suggesting the existence of a possible association between early stress and pain. Therefore, taking EMSs into account could be of great relevance to clinicians. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Role of early extraction of odontogenic focus in deep neck infections

Background: Odontogenic deep neck infections remain a common condition that presents a challenging issue due to the complex involvement of the neck and adjacent structures and its potential life-threatening risk. Periapical infection of the second or third molar with spread to the submandibular and parapharyngeal spaces is the most commonly observed scenario. However, the time of dental extraction of the infection focus remains controversial. The aim of this study is to provide an overview of the epidemiology, clinical and radiological features, and management in patients diagnosed with ODNI and to identify the role of early dental extraction on patient outcomes and recovery. Material and methods: This retrospective study included patients over 18 years old with a diagnosis of ODNI who were admitted to the University Hospital "Dr Jose Eleuterio Gonzalez" from January 2017 to January 2022. ODNI diagnosis was based on clinical and radiological evidence of the disease supplemented by dental and maxillofacial evaluation for an odontogenic aetiology. Results: A total of 68 patients were included in the study. The patients' mean age was 40.96 ± 14.9. Diabetes mellitus was the most common comorbidity. The submandibular space was the most common deep neck space involved (n=59, 86.8%). Mediastinitis, marginal nerve injury and orocervical fistula were observed in 7.5% of patients, with no fatality in this series. A delay of >3 days for dental extraction of the involved tooth was associated with an increased rate of mediastinitis (n=3, 100%, p= 0.022), number of surgical interventions (1.45 ± 0.61, p= 0.006), ICU stay (n=8, 40%, p= 0.019), and ICU length of stay (0.85 ± 0.8, p= 0.001). Conclusions: Expedited management with surgical drainage and intravenous antibiotic treatment, along with early extraction of the involved tooth, is mandatory. (AU)

Effect of intravenous pulses of methylprednisolone 250 mg versus dexamethasone 6 mg in hospitalised adults with severe COVID-19 pneumonia: An open-label randomised trial.

BACKGROUND: The efficacy and safety of high versus medium doses of glucocorticoids for the treatment of patients with COVID-19 has shown mixed outcomes in controlled trials and observational studies. We aimed to evaluate the effectiveness of methylprednisolone 250 mg bolus versus dexamethasone 6 mg in patients with severe COVID-19. METHODS: A randomised, open-label, controlled trial was conducted between February and August 2021 at four hospitals in Spain. The trial was suspended after the first interim analysis since the investigators considered that continuing the trial would be futile. Patients were randomly assigned in a 1:1 ratio to receive dexamethasone 6 mg once daily for up to 10 days or methylprednisolone 250 mg once daily for 3 days. RESULTS: Of the 128 randomised patients, 125 were analysed (mean age 60 ± 17 years; 82 males [66%]). Mortality at 28 days was 4.8% in the 250 mg methylprednisolone group versus 4.8% in the 6 mg dexamethasone group (absolute risk difference, 0.1% [95% CI, -8.8 to 9.1%]; p = 0.98). None of the secondary outcomes (admission to the intensive care unit, non-invasive respiratory or high-flow oxygen support, additional immunosuppressive drugs, or length of stay), or prespecified sensitivity analyses were statistically significant. Hyperglycaemia was more frequent in the methylprednisolone group at 27.0 versus 8.1% (absolute risk difference, -18.9% [95% CI, -31.8 to - 5.6%]; p = 0.007). CONCLUSIONS: Among severe but not critical patients with COVID-19, 250 mg/d for 3 days of methylprednisolone compared with 6 mg/d for 10 days of dexamethasone did not result in a decrease in mortality or intubation.

Síndrome de Mirizzi grado IV. Presentación de un caso

El Síndrome de Mirizzi es una afección derivada del impacto de un lito en el conducto cístico o infundíbulo de la vesícula biliar. La enfermedad litiásica, crónica y complicada de la vesícula biliar es un factor determinante. Se presenta el caso de un paciente con historia de íctero obstructivo, al cual se le diagnosticó inicialmente tumor periampular. Fue reevaluado y se le realizaron varias pruebas diagnósticas, hasta llegar al diagnóstico de Síndrome de Mirizzi, corroborado en el acto quirúrgico. El SM es una enfermedad rara de la vía biliar cuyo tratamiento es quirúrgico. La vía laparoscópica para la realización de la colecistectomía es la de elección para casos grado I y en casos seleccionados grado II. La colecistectomía y derivación bilioentérica (hepaticoyeyunostomía) conforman el tratamiento para el resto de los casos.

Mirizzi Syndrome is a condition derived from the impact of a stone in the cystic duct or infundibulum of the gallbladder. Chronic and complicated stone disease of the gallbladder is a determining factor. A patient with a history of obstructive jaundice, who was initially diagnosed with a periampullary tumor is presented. He was reassessed and several diagnostic tests were performed, until reaching the diagnosis of Mirizzi Syndrome, corroborated in the surgical act. MS is a rare disease of the bile duct whose treatment is surgical. The laparoscopic approach to perform cholecystectomy is the one of choice for grade I cases and in selected cases grade II. Cholecystectomy and bilioenteric bypass (hepaticojejunostomy) are the treatment for the rest of the cases.

A qualitative analysis of internal medicine residents' experience with substance use disorder education and training: a pilot study.

BACKGROUND: Lack of education and training on caring for patients with substance use disorder (SUD) is common among healthcare providers, often resulting in clinicians feeling unprepared to treat patients with SUD. OBJECTIVES: This study explored resident physicians' experiences with SUD education throughout medical school and residency and qualitatively evaluated whether a SUD initiative improved resident's knowledge and efficacy of treating various SUDs. METHODS: We implemented a brief (seven hours total) educational initiative focused on treating SUDs virtually over the course of an academic year for residents enrolled in the University of Southern California Internal Medicine Residency program. Semi-structured interviews were conducted with residents after completion of the initiative. A thematic analysis was conducted to identify common themes that emerged from the qualitative data. RESULTS: Every resident noted receiving insufficient training for the treatment of SUDs prior to the initiative. The initiative was viewed favorably, and participants particularly appreciated having an introduction to prescribing medication for the treatment of SUD such as buprenorphine. Despite the perceived success of the initiative in increasing awareness of treatment modalities for SUD, residents expressed a lack of comfort in handling SUD cases and desired additional practical lectures and application of knowledge through increased experiential training. CONCLUSIONS: SUD education and training appears to be a useful constituent of resident training and should be included in the standard curriculum and rotations. Residency programs should consider including formal education, hands-on practice, and providing adequate resources for residents to develop their capabilities to care for patients with SUD.

Translating the observed differences in interleukin-6 levels between some antiretroviral regimens into potential long-term risk of serious non-AIDS events: A modeling study.

Introduction: Variable levels of systemic inflammation are observed in people with HIV (PWH), but the clinical significance of differences among antiretroviral therapy (ART) regimens on associated levels of inflammatory markers is unclear. Based on data from previous epidemiologic studies that defined the predicted change in risk of serious non-AIDS events (SNAEs)/death by changes in interleukin-6 (IL-6) and D-dimer, we modeled the effects of differences in these markers between specific ART regimens on the long-term risk of clinical outcomes. Methods: We used a Markov model to compare the risk of SNAEs/death with differences in IL-6 and D-dimer levels associated with remaining on specific three-drug regimens versus switching to specific two-drug ART regimens over 5 years of treatment. We used IL-6 and D-dimer data based on trajectories over time from the randomized TANGO and observational AIR studies. Age at model entry was set at 39 years. The primary endpoint was the number needed to treat for one additional SNAE/death. Results: Over 144 weeks, PWH on one of the three-drug regimens studied were predicted to spend 22% more time in the low IL-6 quartile and 13% less time in the high IL-6 quartile compared with those on one of the two-drug regimens. Over 144 weeks, the predicted mean number of SNAEs/deaths per 100 PWH was 5.6 for a three-drug regimen associated with lower IL-6 levels versus 6.8 for a two-drug regimen associated with higher IL-6 levels. The number needed to treat for one additional SNAE/death among PWH receiving a two-drug versus three-drug regimen for 240 weeks was 43. Approximately 2,900 participants would be required for a 240-week clinical study to evaluate the accuracy of the model. Conclusions: Our Markov model suggests that higher IL-6 levels associated with switching from specific three- to two- drug ART regimens may be associated with an increase in the risk of SNAEs/death. Clinical studies are warranted to confirm or refute these results.

Naltrexone for alcohol use disorder: Hepatic safety in patients with and without liver disease.

Naltrexone is an approved drug for management of alcohol use disorder (AUD), but data in patients with liver disease (LD) are limited. We aimed to evaluate the safety of naltrexone in those with LD. This is a retrospective cohort of adults with and without LD who were prescribed naltrexone for AUD from 2015 to 2019 in a safety-net setting. Naltrexone hepatic safety was determined by liver enzyme changes during and after compared to before naltrexone prescription as well as rates of subsequent hospitalization and death by Kaplan-Meier methods. Factors associated with hospitalization were examined by Cox regression. Of 160 patients prescribed naltrexone for AUD, 100 (63%) had LD and 47 (47%) of those with LD had cirrhosis (47% decompensated). The total cohort, LD, and cirrhosis groups had lower adjusted mean aspartate aminotransferase and alanine aminotransferase levels after versus before naltrexone prescription (p < 0.001). Two-year survival was 97.7% (95% confidence interval [CI], 84.6-99.7), 95.4% (95% CI, 82.8-98.8), 90.8% (95% CI, 73.5-97.0), and 81.3% (95% CI, 41.2-93.8) in those without LD, LD without cirrhosis, cirrhosis, and decompensated cirrhosis groups (p = 0.46), respectively. Alcohol-related 2-year hospitalization rates were 8.2% (95% CI, 2.7-24), 27.7% (95% CI, 16.6-44.0), 40.5% (95% CI, 24.8-61.6), and 41.7% (95% CI, 23.3-66.6) for the groups without LD, LD without cirrhosis, cirrhosis, and decompensated cirrhosis (p = 0.007), respectively. Independent predictors of subsequent hospitalization were LD, (hazard ratio [HR], 3.70; 95% CI, 1.19-11.51; p = 0.02), cirrhosis (HR, 5.16; 95% CI, 1.69-15.75), and shorter duration (≤30 days) of naltrexone prescription (HR, 2.50; 95% CI, 1.l2-5.20; p = 0.01). Conclusion: Naltrexone is safe to use in patients with underlying LD, including those with compensated cirrhosis. Although encouraging, more safety data are needed for those with decompensated cirrhosis.

Inflammatory Response, Immunosuppression and Arginase Activity after Cardiac Surgery Using Cardiopulmonary Bypass.

Background: Major surgeries suppress patients' cellular immunity for several days, but the mechanisms underlying this T-cell dysfunction are not well understood. A decreased L-Arginine (L-Arg) level may inhibit T-cell function. Arginase 1 (Arg 1) is induced after traumatic injury, leading to molecular changes in T cells, including decreased expression of cell surface T-cell receptors (TCRs) and a loss in CD3ζ chain expression. In this study, we examined the temporal patterns of CD3ζ expression and Arg 1 activity in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). Methods: We determined the CD3ζ chain expression; the Arg 1 activity; and the leukocyte, neutrophil and lymphocyte levels of patients on the day before surgery and at 24, 48 and 72 h after surgery. Results: Fifty adult patients scheduled for elective cardiac surgery with CPB were eligible for enrolment. Arginase activity was significantly increased between the day before surgery and at 24, 48 and 72 h after surgery (p < 0.01), and CD3ζ expression was significantly decreased between the day before surgery and at 24, 48 and 72 h after surgery (p < 0.001). We observed significant leukocytosis, neutrophilia and lymphopenia after surgery. Conclusions: The decreased CD3ζ chain expression could be due to the increased Arg 1 activity secondary to the activation of neutrophils in cardiac surgery under CPB. These findings could explain the limited immune-system-mediated organ damage resulting from systemic inflammatory response to major cardiac surgery with CPB.