Prevalencia de hipofunción vestibular en el vértigo postural paroxístico benigno post traumatismo craneoencefálico

Introducción: El traumatismo craneoencefálico (TCE) puede generar vértigo, mareo e inestabilidad. Posibles causas otorrinolaringológicas son el vértigo postural paroxístico benigno (VPPB) que constituye el diagnóstico más frecuente, y la hipofunción vestibular. Objetivo: Describir la prevalencia de hipofunción vestibular en un grupo de pacientes con VPPB asociado a TCE. Material y Método: Estudio retrospectivo de pacientes con VPPB asociado a TCE que requirieron maniobra de reposición (MRP) entre los años 2017 y 2021. La información clínica, características clínico-demográficas, hallazgos en pruebas de función vestibular y número de MRP fueron evaluados. Resultados: Se incluyeron 48 pacientes con una edad promedio de 60,8 ± 16,5 años, siendo un 52% mujeres. La prevalencia de pacientes con paresia vestibular concomitante correspondió al 35,4%. Al comparar al grupo con y sin paresia se observó: (1) en el grupo con paresia fue, significativamente, más frecuente presentar contusión cerebral asociada, 47,1% vs 12,9%; (2) el sexo masculino fue, significativamente, más frecuente en el grupo con paresia, 70,59% vs 35,5%; (3) en ambos grupos, la mediana de MRP fue 1. Conclusión: La presencia de paresia vestibular en pacientes con VPPB secundario a TCE, no es un hallazgo infrecuente, en nuestro estudio, correspondió a un 35,4%, siendo este más frecuente en hombres. Adicionalmente, la contusión cerebral asociada es más frecuente en el grupo con paresia.

Introduction: Head trauma can generate vertigo, dizziness and instability. Possible otorhinolaryngologic causes are benign paroxysmal postural vertigo (BPPV), which is the most frequent diagnosis, and vestibular hypofunction. Aim: To describe the prevalence of vestibular hypofunction in a group of patients with BPPV associated with head trauma. We studied the clinical characteristics, vestibular function test findings and the number of (PRM). Material and Method: Retrospective study of patients with BPPV associated with head trauma who underwent particle repositioning maneuvers (PRM) during the years 2017 to 2021. Clinical characteristics, vestibular function test findings and the number of PRM were evaluated. Results: 48 patents were included. The mean age was 60.8 ± 16.5 years old, 52% were women. The prevalence of patients with concomitant vestibular paresis was 35.4%. When comparing the groups with and without paresis the following was observed: (1) associated brain contusions were significatively more frequent in the paresis group, 47.1% vs 12.9%; (2) male sex was significatively more frequent in the paresis group, 70.59% vs 35.5%; (3) in both groups, the median of needed PRM was 1. Conclusion: The presence of vestibular paresis in patients with BPPV secondary to head trauma is not an infrequent finding. In our study, its prevalence was 35.4%, being significatively more frequent in men. Also, associated brain contusions were significatively more frequent in the paresis group.

Safety and efficacy of intravesical instillation of resiniferatoxin in healthy cats: A preliminary study.

Objectives: To evaluate the safety of intravesical application of resiniferatoxin (RTX) in healthy cats and its effects on calcitonin gene-related peptide (CGRP) and substance P (SP) produced by C-fibers. Methods: Seven adult female cats received either 25 mL of saline (control; n = 1), or intravesical RTX at 5, 25, or 50 µg in 25 mL of saline to a final concentration of 0.2 µg/mL (318 nM), 1 µg/mL (1,591 nM), and 2 µg/mL (3,181 nM) (n = 2 per group). The treatment was instilled into the urinary bladder for 20 min. Plasma concentrations of RTX were measured at 0, 0.5, 1, and 4 h. Physical exam, complete blood count, and serum biochemical analysis were performed on day 0, 7, and 14. After 14 days, the sacral dorsal root ganglia (DRG) and the urinary bladder were harvested for histological and immunofluorescence analysis. Results: Intravesical RTX was well tolerated and plasma concentrations were below the quantifiable limits except for one cat receiving 1 µg/mL. Mild to moderate histopathological changes, including epithelial changes, edema, and blood vessel proliferation, were observed at lower doses (0.2 and 1 µg/mL), and were more severe at the higher dose (2 µg/mL). C-fiber ablation was observed in the urinary bladder tissue at all doses, as shown by an apparent reduction of both CGRP and SP immunoreactive axons. Conclusion: A dose of 25 µg (1 µg/mL) of RTX instilled in the urinary bladder of healthy cats appeared to decrease the density of SP and CGRP nerve axons innervating bladder and induced moderate changes in the bladder tissue.

Unintended consequences of COVID-19 safety measures on patients with chronic knee pain forced to defer joint replacement surgery.

In recent months, with the emergence of the COVID-19 pandemic, the American College of Surgeons and the U.S. Centers for Disease Control and Prevention officially recommended the delay of nonemergency procedures until the public health crisis is resolved. Deferring elective joint replacement surgeries for an unknown period is likely to decrease the incidence of infection with SARS-CoV-2 but is likely to have detrimental effects in individuals suffering from chronic knee pain. These detrimental effects extend beyond the discomfort of osteoarthritis (OA) and the inconvenience of rescheduling surgery. Disabling pain is a driving factor for individuals to seek medical intervention, including pharmacological palliative treatment and surgical procedures. The need for surgical intervention due to chronic pain as for knee and hip replacement is now put on hold indefinitely because access to surgical care has been limited. Although a moderate delay in surgical intervention may not produce a significant progression of OA within the knee, it could lead to muscle wasting due to immobility and exacerbate comorbidities, making rehabilitation more challenging. Importantly, it will have an impact on comorbidities driven by OA severity, notably decreased quality of life and depression. These patients with unremitting pain become increasingly susceptible to substance use disorders including opioids, alcohol, as well as prescription and illegal drugs. Appreciation of this downstream crisis created by delayed surgical correction requires aggressive consideration of nonsurgical, nonopiate supported interventions to reduce the morbidity associated with these delays brought upon by the currently restricted access to joint repair.

The role of afferent pulmonary innervation in ARDS associated with COVID-19 and potential use of resiniferatoxin to improve prognosis: A review.

Acute respiratory distress syndrome (ARDS) is one of the major causes of mortality associated with COVID-19 disease. Many patients will require intensive care with ventilatory support. Despite progress and best efforts, the mortality rates projected remain high. Historical data outlook points towards 80% expected fatality for patients progressing to advanced pulmonary disease, even when hospitalized in the intensive care unit. This is particularly true among the patient population over 65. Novel life-saving strategies are desperately needed to mitigate the high mortality that will be associated with the late stage SARS-CoV-2 viral infection associated with the fatal respiratory distress. We hypothesize that the morbidity, severity of the disease, and underlying physiological events leading to mortality are closely linked to the TRPV1 expressing neuronal system (afferent/efferent neurons) in the lungs. TRPV1 expressing cells are responsible for pain transmission, inflammation and immunomodulation throughout the entire pulmonary system and are modulating the processes associated with localized cytokine release (storm) and overall rapid disease progression. We suggest that therapeutic approaches targeting TRPV1 containing nerve fibers in the lungs will modulate the inflammatory and immune signal activity, leading to reduced mortality and better overall outcomes. We also propose to further explore the use of resiniferatoxin (RTX), an ultra-potent TRPV1 agonist currently in clinical trials for cancer and osteoarthritis pain, as a possible ablating agent of TRPV1 positive pulmonary pathways in patients with advanced COVID-19 disease.

The Prevalence of Rheumatoid Arthritis in Chile: A Nationwide Study Performed as Part of the National Health Survey.

OBJECTIVE: Genetic and environmental backgrounds influence the development of rheumatoid arthritis (RA). In Latin America, epidemiologic data are scarce. We aimed to determine the prevalence of RA in Chile in a population-based study. METHODS: The National Health Survey was a cross-sectional household survey with a stratified multistage probability sample of 6233 participants performed between August 2016 and March 2017. A screening instrument for RA was applied to a random sample of 3847 subjects > 30 years old. Positive screening was defined by at least 1 of the following: 2 swollen joints for at least 4 consecutive weeks (past/present), and/or a diagnosis of arthritis in the past. Individuals with positive screening had rheumatoid factor, anticitrullinated protein antibodies, and C-reactive protein measured, as well as clinical examination performed by a rheumatologist. Self-report of doctor-diagnosed RA was also performed. RESULTS: The screening questionnaire was applied to 2998 subjects. A positive screening was found for 783 (22.1%). Among subjects with positive screening, 493 (66%) had a clinical evaluation performed by a rheumatologist. Using the American College of Rheumatology/European League Against Rheumatism 2010 classification criteria, prevalence was 0.6% (95% CI 0.3-1.2). Prevalence was higher in women, and 3.3% of subjects self-reported having RA. CONCLUSION: According to this national population-based study, RA prevalence in Chile is 0.6% (0.3-1.2), a value similar to what has been found in developed countries and slightly lower than some Latin American countries. Self-reporting leads to overestimating RA.

Target engagement and histopathology of neuraxial resiniferatoxin in dog.

OBJECTIVE: To evaluate target engagement of intracisternally (IC) delivered TRPV1 agonist, resiniferatoxin (RTX), as measured by primary afferent and dorsal horn substance P immunoreactivity (sP-IR), histopathology and thermal escape latencies in dogs. STUDY DESIGN: Prospective experimental trial. ANIMALS: Fourteen adult male Beagle dogs, weighing 10.3-13.2 kg; 11 dogs surviving to scheduled euthanasia. METHODS: Anesthetized dogs were randomly assigned to be administered IC RTX (3.6 µg, 0.1 mL kg-1) in a hyperbaric (hRTX, n = 6), normobaric (nRTX, n = 4) vehicle or a hyperbaric vehicle (hVehicle, n = 4). Over 16 days, animals were examined for thoracic and pelvic limb paw thermal withdrawal latencies and neurologic function. Spinal cords, trigeminal ganglia and dorsal root ganglia (DRGs) were assessed for morphologic changes and sP-IR. RESULTS: IC RTX in anesthetized dogs resulted in a < 1 hour increase in blood pressure. Acute reactions leading to euthanasia within 8 hours occurred in three dogs (two hRTX, one nRTX). All other animals recovered with normal neurologic, bowel and bladder function. Final groups were: vehicle n = 4, hRTX n = 4 and nRTX n = 3. Animals in nRTX and hRTX showed increases in escape latencies in thoracic paws and, to a lesser extent, in pelvic paws, correlating to a loss of sP-IR in cervical cord with smaller reductions in thoracic and lumbar cord. In animals surviving to euthanasia, thickening of the arachnoid membrane (predominantly in the cervical region) was the most consistent change. This change, present in controls, was interpreted to be vehicle related. There was no evidence of structural changes in brain and spinal cord. CONCLUSIONS AND CLINICAL RELEVANCE: IC RTX produced localized loss of spinal and DRG sP with a corresponding thermal analgesia, absent motor impairment or spinal pathology. Loss of three animals emphasizes the need to refine the use of this promising therapeutic modality in managing companion animal pain.

Toxicology Evaluation of Drugs Administered via Uncommon Routes: Intranasal, Intraocular, Intrathecal/Intraspinal, and Intra-Articular.

As the need for nasal, ocular, spinal, and articular therapeutic compounds increases, toxicology assessments of drugs administered via these routes play an important role in human safety. This symposium outlined the local and systemic evaluation to support safety during the development of these drugs in nonclinical models with some case studies. Discussions included selection of appropriate species for the intended route; conducting nonclinical studies that closely mimic the intended use with adequate duration; functional assessment, if deemed necessary; evaluation of local tissues with special histological staining procedure; and evaluations of safety margins based on local and systemic toxicity.

Changes in blood volume indicators and dynamic indicators measured with transpulmonary ultrasound velocity during blood depletion and repletion in a neonatal swine model.

BACKGROUND: Dynamic indicators such as pulse pressure and stroke volume variations can be measured to track changes in preload during hemorrhage, and evaluate fluid therapy. However, these dynamic indicators require mechanical ventilation, and might be affected by cardiac dysrhythmias and changes in vascular tone. Blood volume indicators may offer alternatives for assessing changes in volume status. AIMS: The aims of this study were to measure changes in blood volume indicators and dynamic indicators during removal of blood in two stages and subsequent blood replacement in anesthetized, mechanically ventilated, neonatal pigs. METHODS: In eight anesthetized, mechanically ventilated piglets (5-6 weeks old), cardiac index, stroke volume index, total end-diastolic volume, central blood volume, active circulating volume, pulse pressure variation, and stroke volume variation were measured during blood removal in two stages (15 mL kg-1 each stage) and blood replacement (30 mL kg-1 ). Values after each intervention were measured for each parameter. RESULTS: All indicators differed from baseline after removal of 15 mL kg-1 of blood, except for stroke volume variation. Differences between both stages of hemorrhage were only observed for indexed stroke volume, total end-diastolic volume, central blood volume, and pulse pressure variation. CONCLUSION: Total end-diastolic volume and central blood volume changed during blood depletion and repletion, and differed between stages of hemorrhage. These indicators might be useful for assessing volume status instead of, or in addition to cardiac index and dynamic indicators.

Continuous minimally invasive cardiac output monitoring with the COstatus in a neonatal swine model: recalibration is necessary during vasoconstriction and vasodilation.

BACKGROUND: The COstatus monitor measures cardiac output via the transpulmonary ultrasound dilution method (COTPUD ) after injection of normal saline, and can calculate continuous cardiac output (CCO) from the arterial pressure waveform. The relationship between arterial waveform and COTPUD however, might be degraded during vasoconstriction/vasodilation. OBJECTIVES: To examine if recalibration of arterial waveform-derived CCO is required during mild vasoconstriction/vasodilation. METHODS: In 10 anesthetized piglets (6.6-10.1 kg), two COstatus monitors calculated the CCO from the same femoral arterial waveform before and during infusions of phenylephrine (PE; 1 or 3 mg·kg(-1) ·min(-1) ) and sodium nitroprusside (SNP; 1 or 5 mg·kg(-1) ·min(-1) ), administered in random order. One monitor was recalibrated (CCORecal ) after each intervention, while the other monitor was not (CCONon-Recal ). Recalibration was performed with COTPUD with 1 ml·kg(-1) normal saline as indicator. The effects of each infusion on hemodynamic parameters were compared with baseline using paired t-tests. The bias, limits of agreement (LOA), and percentage error between simultaneous measurements (CCORecal and CCONon-Recal ) were examined with Bland-Altman plots. RESULTS: Infusion of PE significantly increased COTPUD , heart rate (HR), and arterial pressures but not systemic vascular resistance (SVR). Infusion of SNP decreased arterial pressures without affecting COTPUD , HR, and SVR. There was no bias between CCORecal and CCONon-Recal at the baseline, but a small bias was observed during PE and SNP infusions. The LOA increased approximately 10 fold during vasoconstriction and vasodilation. The percentage error increased from ≤ 5% to 32% and 27% during PE and SNP infusions, respectively. CONCLUSION: Continuous cardiac output (CO) measured with the COstatus monitor requires recalibration during vasoconstriction and vasodilation, even if changes in COTPUD or SVR are not substantial.