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BACKGROUND: The mechanism of bilirubin neurotoxicity is poorly understood. We hypothesize that bilirubin inhibits the function of lipid rafts (LR), microdomains of the plasma membrane critical for signal transduction. To test this hypothesis, we measured the effect of free bilirubin (Bf) between 7.6 and 122.5 nM on LR-dependent functions of L1 cell adhesion molecule (L1). METHODS: Cerebellar granule neurons (CGN) were plated on poly-L-lysine overnight, and neurite length was determined after 1 h treatment with L1 alone or L1 and bilirubin. L1 activation of ERK1/2 was measured in CGN in the presence or absence of bilirubin. The effect of bilirubin on L1 distribution in LR was quantitated, and the localization of bilirubin to LR was determined. RESULTS: The addition of bilirubin to CGN treated with L1 significantly decreased neurite length compared to L1 alone. L1 activation of ERK1/2 was inhibited by bilirubin. Bilirubin redistributed L1 into LR. Bilirubin was associated only with LR-containing fractions of a sucrose density gradient. CONCLUSION: Bf significantly inhibits LR-dependent functions of L1 and are found only associated with LR, suggesting one mechanism by which bilirubin may exert neurotoxicity is through the dysfunction of protein-LR interactions. IMPACT: This article establishes lipid rafts as a target for the neurotoxic effects of bilirubin. This article provides clear evidence toward establishing one mechanism of bilirubin neurotoxicity, where little is understood. This article paves the way for future investigation into lipid raft dependent functions, and its role in neurodevelopmental outcome.
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Bilirrubina/farmacología , Cerebelo/metabolismo , Gránulos Citoplasmáticos/metabolismo , Microdominios de Membrana/efectos de los fármacos , Molécula L1 de Adhesión de Célula Nerviosa/fisiología , Neuronas/metabolismo , Animales , Ratas , Ratas Sprague-DawleyAsunto(s)
Anestesiología , Neoplasias , Anestesiólogos , Niño , Humanos , Estudios Retrospectivos , Sociedades Médicas , Estados UnidosRESUMEN
Adductor canal block is a widely used regional anesthesia technique for total knee arthroplasty that helps in reducing post-surgical pain and opioid use. Anatomically, the adductor canal extends from the apex of the femoral triangle proximally to the adductor hiatus distally and is roofed by the sartorius and vasto-adductor fascia. All these serve as a potential path for the spread of the local anesthetic when it is injected inside the adductor canal during the block. Subsartorial space is of unique interest as it lies between the sartorius and vasto-adductor fascia, carrying the subsartorial plexus that can provide additional analgesia to the knee when the adductor canal block injectate spreads into it. While the spread can be variable, ultrasound can be a useful tool to evaluate this spread. This is a case series of patients who underwent total knee arthroplasty under spinal anesthesia and adductor canal blocks. We present the findings of ultrasound evaluation of the injectate spread following adductor canal blocks and evaluation of their analgesia effects.
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Scapulalgia or shoulder pain accounts for 16% of all musculoskeletal complaints in the healthy adult population and becomes more common as we age. When this pain exceeds 3 months in duration, it is deemed to be chronic, and typically treated in an escalating manner. Spanning a continuum of conservative and non-conservative measures, chronic shoulder pain treatments range from rest and physical therapy to surgery. Since each patient presents with a unique spectrum of symptoms a customized treatment plan is often required. Over the lifetime of many of these patients, a variety of treatment options are required. One of these treatment options, peripheral nerve stimulation (PNS), is a minimally invasive procedure in which an electrical impulse is delivered through a percutaneously implanted, small caliber electrode to a peripheral nerve proximal to the lesion which interferes with the pain signals. Over the past several years, significant growth of PNS in the treatment of chronic neuropathic pain has been observed. However, the procedural techniques have not been well described. The foundation of long-term, minimally invasive percutaneous PNS in patients with chronic shoulder pain, and procedural techniques for stimulating the suprascapular and axillary nerves using fluoroscopy or ultrasonography will be described in this report.
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Appropriate specimen handling is integral to quality and minimizing medical errors. Clinical laboratories often rely on manufacturer's claims for handling specimens, such as sample stability conditions. Serum angiotensin converting enzyme (ACE) is an example in which manufacturer claims and stability in the literature is limited. The purpose of this study was to demonstrate the importance to verify manufacturer's stability using serum ACE as an example. Serum was collected from 39 healthy volunteers and ACE activity levels measured at baseline, after 4 h, 1, 3, 7 days at room temperature, after 3, 7, and 14 days refrigerated at 4 °C, after 1, 2, 4 and 8 weeks frozen at -20 °C, and after three freeze/thaw cycles. An additional 42 discarded patient serum specimens were re-analyzed after 1 or 2 weeks frozen at -20 °C. To evaluate stability performance, percent difference was compared to the clinical acceptance criteria, which was defined as a ½ total allowable error of ±10.9 %. This study found serum ACE to be stable 4 h at room temperature, 14 days refrigerated at 4 °C, up to 1 week frozen at -20 °C, and up to three freeze/thaw cycles. The preferred storage condition for serum ACE is refrigerated at 4 °C as there was minimal change in percent bias over the 14 day period. The false increase observed in samples stored frozen longer than 1 week could impact clinical decision making. The stability findings differed from manufacturer claims, highlighting the importance of verifying stability, especially for esoteric testing such as serum ACE where specimens travel long distances in varying climates to reach centralized testing locations.
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Servicios de Laboratorio Clínico , Peptidil-Dipeptidasa A , Humanos , Temperatura , Manejo de Especímenes , Laboratorios ClínicosRESUMEN
AIMS: Whether electrocardiographic (ECG) measurements predict mortality in chronic heart failure with reduced ejection fraction (HFrEF) is unknown. METHODS AND RESULTS: We studied 4880 patients from the Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction (VICTORIA) trial with a baseline 12-lead ECG. Associations between ECG measurements and mortality were estimated as hazard ratios (HR) and adjusted for the Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) risk score, N-terminal pro-B-type natriuretic peptide, and index event. Select interactions between ECG measurements, patient characteristics and mortality were examined. Over a median of 10.8 months, there were 824 cardiovascular (CV) deaths (214 sudden) and 1005 all-cause deaths. Median age was 68 years (interquartile range [IQR] 60-76), 24% were women, median ejection fraction was 30% (IQR 23-35), 41% had New York Heart Association class III/IV, and median MAGGIC score was 24 (IQR 19-28). After multivariable adjustment, significant associations existed between heart rate (per 5 bpm: HR 1.02), QRS duration (per 10 ms: HR 1.02), absence of left ventricular hypertrophy (HR 0.64) and CV death, and similarly so with all-cause death (HR 1.02; HR 1.02; HR 0.61, respectively). Contiguous pathologic Q waves were significantly associated with sudden death (HR 1.46), and right ventricular hypertrophy with all-cause death (HR 1.44). The only sex-based interaction observed was for pathologic Q waves on CV (men: HR 1.05; women: HR 1.64, pinteraction = 0.024) and all-cause death (men: HR 0.99; women: HR 1.57; pinteraction = 0.010). Whereas sudden death doubled in females, it did not differ among males (male: HR 1.25, 95% confidence interval [CI] 0.87-1.79; female: HR 2.50, 95% CI 1.23-5.06; pinteraction = 0.141). CONCLUSION: Routine ECG measurements provide additional prognostication of mortality in high-risk HFrEF patients, particularly in women with contiguous pathologic Q waves.
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Insuficiencia Cardíaca , Disfunción Ventricular Izquierda , Anciano , Femenino , Humanos , Masculino , Muerte Súbita , Electrocardiografía , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/epidemiología , Volumen Sistólico/fisiología , Persona de Mediana EdadRESUMEN
BACKGROUND: A supraclavicular brachial plexus nerve block provides analgesia for the shoulder, arm, and hand; however, the maximum safe duration for a continuous infusion remains controversial. A novel continuous peripheral nerve block (CPNB) technique combining the Lateral, Intermediate, and Medial femoral cutaneous nerves (termed the 'LIM' block) to provide analgesia to the lateral, anterior, and medial cutaneous areas of the thigh while preserving quadriceps strength will also be described in detail here. CASE: We present a complex case in which simultaneous utilization of an unilateral supraclavicular CPNB (5 weeks) and bilateral LIM CPNB (5 days) are successfully performed to provide analgesia for a traumatic degloving injury resulting in multiple surgeries. CONCLUSIONS: The analgesic plan in this case study eliminated previous episodes of opioid-induced delirium, facilitated participation in recovery, and removed concerns for respiratory depression and chronic opioid use in a patient at particular risk for both issues.
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Coronavirus disease (COVID-19) causes many deleterious effects throughout the body. Prior studies show that the incidence of acute kidney injury in COVID-19 patients could be as high as 25%. There are also autopsy reports showing evidence of viral tropism to the renal system. In this regard, COVID-19 can damage the kidneys and increase a patient's risk of requiring dialysis. Available evidence suggests that renal involvement in COVID-19 infection is not uncommon, and there has been an increased incidence of chronic kidney disease related to the pandemic. In this literature analysis, we address COVID-19 and its effects on the renal system, including the pathophysiologic mechanisms. We also address current studies on the causes of injury to the renal system, the cause of kidney failure, its effect on mortality, the impact on dialysis patients, and the impact on renal transplant patients. COVID-19 disease may have unique features in individuals on chronic dialysis and kidney transplant recipients, requiring increased vigilance in limiting viral transmission in perioperative, in-patient, and dialysis center settings.
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COVID-19/fisiopatología , Enfermedades Renales/fisiopatología , Riñón/fisiopatología , COVID-19/epidemiología , COVID-19/terapia , Humanos , Riñón/virología , Enfermedades Renales/epidemiología , Enfermedades Renales/terapia , Enfermedades Renales/virología , Diálisis Renal/métodos , Diálisis Renal/tendencias , Resultado del TratamientoRESUMEN
Point of care glucose (POCG) measurements, used for detecting neonatal hypoglycemia, can have variable accuracy. The appropriate diagnosis of neonatal hypoglycemia in babies with low POCG measurements involves confirmatory serum glucose (CSG) testing. At our institution, no babies with low POCG measurements had CSG testing in their evaluation of neonatal hypoglycemia over a three year period. Our aim was to increase the percentage of CSG testing in babies with a low POCG. A secondary aim was to decrease the percentage of low-risk, asymptomatic babies who received POCG testing. Interventions included the design and implementation of an evidence-based protocol for the diagnosis and management of neonatal hypoglycemia (cycle 1), along with supportive education for multi-disciplinary providers on best practices related to neonatal hypoglycemia (cycle 2). Data were analyzed using statistical process control. During Cycle 1, the percentage of CSG testing in babies with POCG ≤40 mg/dL significantly increased from 0 to 33%, and increased further to 63% during Cycle 2. The initial gain was sustained over 2 years. The percentage of POCG testing among low-risk asymptomatic babies was 40% at baseline and did not change during the project period. 18 babies with low POCG results were spared from a diagnosis of neonatal hypoglycemia based on CSG testing. Implementation of a neonatal hypoglycemia protocol, along with supportive education, significantly improved rates of CSG testing, but not POCG overutilization, in our newborn population. Factors related to POCG overutilization should be further explored.