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1.
Am J Ther ; 31(2): e97-e103, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38518266

RESUMEN

BACKGROUND: Psychedelic drugs have recently emerged as plausibly effective pharmacological agents for the management of depression, anxiety, and other neuropsychiatric conditions, including those that are treatment-resistent. The latter half of the 20th century marked a revolution in the treatment of mental illnesses, exemplified by the introduction of selective serotonin reuptake inhibitors and other pharmacological agents. Nevertheless, mental illness remains a major public health crisis, affecting nearly one billion individuals worldwide. AREAS OF UNCERTAINTY: Because of the decades-long status of several psychedelics as Schedule I drugs, there have not been very many large, double-blind, randomized controlled trials of psychedelics. Owing to small sample sizes, there may be rare yet serious adverse events that have not been reported in the clinical trials thus far. THERAPEUTIC ADVANCES: Esketamine, a dissociative hallucinogen drug, was approved for the management of major depressive disorder by the Food and Drug Administration in 2019. As of January 2024, two Phase III trials of 3,4-methylenedioxymethamphetamine (MDMA), a synthetic drug that inhibits the serotonin transporter, have been completed; the results indicate that MDMA is superior to existing pharmacological treatments for post-traumatic stress disorder. A phase III trial of psilocybin, a naturally occurring serotonin receptor partial agonist, is currently underway. The following series details the current state of research in psychedelic therapeutics, including lysergic acid diethylamide (LSD), N-N-dimethyltryptamine (DMT) and ayahuasca, psilocybin, ibogaine, MDMA, and ketamine. LIMITATIONS: While initial clinical trials of psychedelics for depression were very promising, trials of psilocybin with larger sample sizes (100+ participants) suggest that its remission rate is 25%-29%. This is about the same as the remission rate of antidepressants, which is roughly 30% according to the landmark STAR*D trial. CONCLUSIONS: Psychedelic drugs and structural derivatives offer a great deal of promise for the management of a wide range of psychiatric morbidities. It is imperative that clinicians become familiar with these novel agents and learn how to integrate psychedelic therapy with the rest of their care through open communication and referral.


Asunto(s)
Trastorno Depresivo Mayor , Alucinógenos , Humanos , Trastorno Depresivo Mayor/tratamiento farmacológico , Alucinógenos/farmacología , Alucinógenos/uso terapéutico , N-Metil-3,4-metilenodioxianfetamina/farmacología , N-Metil-3,4-metilenodioxianfetamina/uso terapéutico , Atención Primaria de Salud , Psilocibina/farmacología , Psilocibina/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto
2.
Am J Ther ; 31(2): e104-e111, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38518267

RESUMEN

BACKGROUND: Lysergic acid diethylamide (LSD) is a hallucinogenic agent. In the mid-20th century, it was used to augment psychoanalysis and to treat alcohol use disorder. However, LSD was banned in 1970 in part because of concerns that it could bring about or exacerbate mental illness. Its therapeutic potential remains incompletely understood. AREAS OF UNCERTAINTY: While uncontrolled recreational use of LSD can, in rare instances, lead to long-term psychosis, adverse events in clinical trials of LSD, such as anxiety, headache, and nausea, have almost always been mild and transient. Serious adverse events, such as intense panic, suicidal ideation, and psychosis, were reported in either none or very few of the participants. However, patient selection criteria, optimal dosing strategy, and appropriate clinical follow-up guidelines remain to be established. THERAPEUTIC ADVANCES: Preliminary data suggest that LSD may be effective for the management of alcohol use disorder, anxiety, and depression. In trials of LSD for treating anxiety and depression associated with life-threatening illnesses, 77% of participants demonstrate durable relief at 1 year post-treatment. Top-line data from a large-scale phase IIb trial (n = 198) indicate that 50% of participants experience remission from generalized anxiety disorder after a single 100 µg dose of LSD. According to a meta-analysis of RCTs on LSD from the mid-20th century, single-dose regimens of LSD significantly improve alcohol use disorder (P < 0.0003) with an odds ratio (OR) of 1.96. LIMITATIONS: Only one large-scale clinical trial (>50 participants) has been conducted on LSD in the contemporary era of psychedelic research. Further studies with large sample sizes are needed to explore potential clinical applications. CONCLUSIONS: Preliminary data suggest that LSD may be one of the most potent treatments for anxiety in patients both with and without a life-threatening illness. LSD may also be beneficial for treating depression and substance use disorders.


Asunto(s)
Alcoholismo , Alucinógenos , Humanos , Trastornos de Ansiedad/tratamiento farmacológico , Alucinógenos/efectos adversos , Alucinógenos/uso terapéutico , Dietilamida del Ácido Lisérgico/uso terapéutico , Dietilamida del Ácido Lisérgico/efectos adversos , Atención Primaria de Salud , Metaanálisis como Asunto , Ensayos Clínicos como Asunto
3.
Am J Ther ; 31(2): e133-e140, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38518270

RESUMEN

BACKGROUND: Ibogaine is a plant-derived alkaloid that has been used for thousands of years in rites of passage and spiritual ceremonies in West-Central Africa. In the West, it has primarily been used and studied for its anti-addictive properties and more recently for other neuropsychiatric indications, including post-traumatic stress disorder, depression, anxiety, and traumatic brain injury. AREAS OF UNCERTAINTY: Ibogaine requires careful patient screening and monitoring because of significant safety issues. There is potential for cardiotoxicity (prolonged QT interval); without rigorous screening, fatal arrhythmias may occur. However, preliminary research suggests that co-administration of ibogaine with magnesium may mitigate cardiotoxicity. Additionally, ibogaine may have dangerous interactions with opiates, so patients who receive ibogaine treatment for opioid use disorder must withdraw from long-acting opioids. Other potential concerning effects of ibogaine include rare incidences of mania or psychosis. Anticipated transient effects during ibogaine treatment can include ataxia, tremors, and gastrointestinal symptoms. THERAPEUTIC ADVANCES: Robust effects after a single treatment with ibogaine have been reported. In open-label and randomized controlled trials (RCTs), ibogaine reduces heroin and opioid cravings by upwards of 50%, up to 24 weeks after the treatment. An observational study of 30 Special Operations Forces veterans with mild traumatic brain injury reported that 86% were in remission from post-traumatic stress disorder, 83% from depression, and 83% from anxiety, one month after a single-dose ibogaine treatment. LIMITATIONS: Although there are several observational and open-label studies, there is only a single double-blind, placebo-controlled RCT on ibogaine. More RCTs with large sample sizes must be conducted to support ibogaine's safety and efficacy. CONCLUSIONS: Given the promising preliminary findings, ibogaine could potentially fill a much-needed gap in treatments for challenging conditions, including opioid dependence. Ibogaine's remarkable effects in traditionally treatment-resistant, combat-exposed individuals hints at its potential in broader populations with physical and psychological trauma.


Asunto(s)
Alucinógenos , Ibogaína , Síndrome de QT Prolongado , Trastornos Relacionados con Opioides , Humanos , Cardiotoxicidad/tratamiento farmacológico , Alucinógenos/efectos adversos , Ibogaína/efectos adversos , Síndrome de QT Prolongado/tratamiento farmacológico , Trastornos Relacionados con Opioides/tratamiento farmacológico , Atención Primaria de Salud , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Observacionales como Asunto
4.
Am J Ther ; 31(2): e112-e120, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38518268

RESUMEN

BACKGROUND: N,N-dimethyltryptamine (DMT) is a naturally occurring serotonergic psychedelic found in natural plants around the globe. As the main psychoactive component in ayahuasca, which also contains monoamine oxidase inhibitors, DMT has been consumed as plant-based brew by indigenous peoples for centuries. Further research is required to delineate the therapeutic utility of DMT. AREAS OF UNCERTAINTY: Although previous research has shown that DMT is synthesized endogenously, it may not be produced at physiologically relevant concentrations. Additionally, the phenomenological similarities between the DMT-induced state and near-death experiences led to the popular hypothesis that endogenous DMT is released during the dying process. However, this hypothesis continues to be debated. Generally, DMT and ayahuasca seem to be physiologically and psychiatrically safe, although ayahuasca is known to cause transient vomiting. THERAPEUTIC ADVANCES: A double-blind, randomized controlled trial showed that, within 1 week, ayahuasca causes remission in 36% of patients with treatment-resistant depression. According to top-line results from a recent phase IIa trial, 57% of patients with major depressive disorder experienced remission 12 weeks after receiving a single intravenous dose of DMT. LIMITATIONS: There has only been a single published double-blind randomized controlled trial on ayahuasca and 2 on DMT. All clinical trials have had small sample sizes (≤34 participants). DMT requires further research to understand its therapeutic and clinical potential as a psychedelic. CONCLUSIONS: Preliminary evidence indicates that ayahuasca and DMT may be more effective than existing antidepressants for treating major depressive disorder and treatment-resistant depression.


Asunto(s)
Banisteriopsis , Trastorno Depresivo Mayor , Alucinógenos , Humanos , Trastorno Depresivo Mayor/tratamiento farmacológico , Alucinógenos/farmacología , Alucinógenos/uso terapéutico , N,N-Dimetiltriptamina/farmacología , N,N-Dimetiltriptamina/uso terapéutico , Atención Primaria de Salud , Ensayos Clínicos Controlados Aleatorios como Asunto
5.
Am J Ther ; 31(2): e141-e154, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38518271

RESUMEN

BACKGROUND: After becoming notorious for its use as a party drug in the 1980s, 3,4-methylenedioxy-methampetamine (MDMA), also known by its street names "molly" and "ecstasy," has emerged as a powerful treatment for post-traumatic stress disorder (PTSD). AREAS OF UNCERTAINTY: There are extensive data about the risk profile of MDMA. However, the literature is significantly biased. Animal models demonstrating neurotoxic or adverse effects used doses well beyond the range that would be expected in humans (up to 40 mg/kg in rats compared with roughly 1-2 mg/kg in humans). Furthermore, human samples often comprise recreational users who took other substances in addition to MDMA, in uncontrolled settings. THERAPEUTIC ADVANCES: Phase III clinical trials led by the Multidisciplinary Association for Psychedelic Studies (MAPS) have shown that MDMA-assisted psychotherapy has an effect size of d = 0.7-0.91, up to 2-3 times higher than the effect sizes of existing antidepressant treatments. 67%-71% of patients who undergo MDMA-assisted psychotherapy no longer meet the diagnostic criteria for PTSD within 18 weeks. We also describe other promising applications of MDMA-assisted psychotherapy for treating alcohol use disorder, social anxiety, and other psychiatric conditions. LIMITATIONS: Thus far, almost all clinical trials on MDMA have been sponsored by a single organization, MAPS. More work is needed to determine whether MDMA-assisted therapy is more effective than existing nonpharmacological treatments such as cognitive behavioral therapy. CONCLUSIONS: Phase III trials suggest that MDMA is superior to antidepressant medications for treating PTSD. Now that MAPS has officially requested the Food and Drug Administration to approve MDMA as a treatment for PTSD, legal MDMA-assisted therapy may become available as soon as 2024.


Asunto(s)
Alucinógenos , Metanfetamina , N-Metil-3,4-metilenodioxianfetamina , Trastornos por Estrés Postraumático , Animales , Humanos , Ratas , Antidepresivos/uso terapéutico , Ensayos Clínicos Fase III como Asunto , Alucinógenos/uso terapéutico , Metanfetamina/uso terapéutico , N-Metil-3,4-metilenodioxianfetamina/uso terapéutico , N-Metil-3,4-metilenodioxianfetamina/farmacología , Atención Primaria de Salud , Psicoterapia , Trastornos por Estrés Postraumático/tratamiento farmacológico , Trastornos por Estrés Postraumático/psicología
6.
Am J Ther ; 31(2): e178-e182, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38518273

RESUMEN

The reviews in this special edition have presented a primer on the state of the literature for 7 different psychedelic compounds and their plausible roles in medicine. In a common format underscoring strengths, weakness, opportunities, and threats (SWOT), this article addresses how psychedelic compounds fit into the broader health care landscape for indicated conditions. Historically, psychiatric pathologies have been treated with small-molecule compounds that have limited effect sizes and carry a variety of adverse effect profiles. Psychedelic medicines offer the opportunity to provide more potent and rapidly acting treatments. It is crucial to note that this is an emerging field of medicine, and only one of these compounds (esketamine) is currently Food and Drug Administration-approved for depression. The other compounds discussed are investigational, and this discussion is both imaginative and prospective in nature.


Asunto(s)
Alucinógenos , Humanos , Alucinógenos/farmacología , Alucinógenos/uso terapéutico , Estudios Prospectivos , Atención Primaria de Salud
7.
Am J Ther ; 31(2): e155-e177, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38518272

RESUMEN

BACKGROUND: Ketamine, an arylcyclohexylamine dissociative anesthetic agent, has evolved into a versatile therapeutic. It has a rapid-onset, well-understood cardiovascular effects and a favorable safety profile in clinical use. Its enantiomeric compound, esketamine, was approved by the Food and Drug Administration in 2019 for both treatment-resistant depression and major depressive disorder with suicidal ideation. AREAS OF UNCERTAINTY: Research indicates dose-dependent impacts on cognition, particularly affecting episodic and working memory following both acute administration and chronic use, albeit temporarily for the former and potentially persistent for the latter. Alongside acute risks to cardiovascular stability, ketamine use poses potential liver toxicity concerns, especially with prolonged or repeated exposure within short time frames. The drug's association with "ketamine cystitis," characterized by bladder inflammation, adds to its profile of physiological risks. THERAPEUTIC ADVANCES: Data demonstrate a single intravenous infusion of ketamine exhibits antidepressant effects within hours (weighted effect size averages of depression scores (N = 518) following a single 0.5 mg/kg infusion of ketamine is d = 0.96 at 24 hours). Ketamine is also effective at reducing posttraumatic stress disorder (PTSD) symptom severity following repeated infusions (Clinician-Administered PTSD Scale scores: -11.88 points compared with midazolam control). Ketamine also decreased suicidal ideation in emergency settings (Scale for Suicidal Ideation scores: -4.96 compared with midazolam control). Through its opioid-sparing effect, ketamine has revolutionized postoperative pain management by reducing analgesic consumption and enhancing recovery. LIMITATIONS: Many studies indicate that ketamine's therapeutic effects may subside within weeks. Repeated administrations, given multiple times per week, are often required to sustain decreases in suicidality and depressive symptoms. CONCLUSIONS: Ketamine's comprehensive clinical profile, combined with its robust effects on depression, suicidal ideation, PTSD, chronic pain, and other psychiatric conditions, positions it as a substantial contender for transformative therapeutic application.


Asunto(s)
Trastorno Depresivo Mayor , Alucinógenos , Ketamina , Humanos , Ketamina/efectos adversos , Alucinógenos/uso terapéutico , Trastorno Depresivo Mayor/tratamiento farmacológico , Trastorno Depresivo Mayor/psicología , Midazolam , Atención Primaria de Salud , Depresión/tratamiento farmacológico
8.
Am J Ther ; 31(2): e121-e132, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38518269

RESUMEN

BACKGROUND: The primary psychoactive drug in magic mushrooms, psilocybin, induces profound alterations in consciousness through the 5-HT2A receptor. This review consolidates current research findings to elucidate the pharmacology, safety profile, and clinical applications of psilocybin. AREAS OF UNCERTAINTY: Despite initial concerns that psilocybin could cause psychosis, contemporary research has demonstrated that psilocybin is generally safe. The most common adverse effects are nausea and headache, yet both tend to be transient. Serious adverse events can generally be avoided in controlled settings such as clinical trials. However, in the largest clinical trial to date, there were a total of 7 reported cases of suicidal ideation, up to 12 weeks after receiving a single 25 mg dose of psilocybin. That being said, all 7 cases did not respond to the treatment. Although selective serotonin reuptake inhibitors may blunt the hallucinogenic qualities of psilocybin, preliminary research suggests that they may enhance its antidepressant effects. THERAPEUTIC ADVANCES: In clinical trials, psilocybin has shown promise for treating major depressive disorder and treatment-resistant depression. Initial studies indicated that 42%-57% of patients underwent remission after psilocybin-assisted therapy, which suggests that psilocybin is more effective than existing antidepressant medications. Clinical data have also demonstrated that psilocybin can manage substance use disorders and end-of-life anxiety with clinical outcomes that are sustained for months and sometimes years after 1 or 2 doses. LIMITATIONS: However, larger Phase II trials with more than 100 depressed participants have shown a much smaller remission rate of 25%-29%, though these studies still observed that psilocybin causes a significant reduction in depressive symptoms. CONCLUSIONS: Aside from ketamine, psilocybin is the most clinically well-researched psychedelic drug, with trials that have enrolled hundreds of participants and multiple therapeutic applications. Phase III trials will determine whether psilocybin lives up to the promise that it showed in previous clinical trials.


Asunto(s)
Trastorno Depresivo Mayor , Alucinógenos , Humanos , Antidepresivos/efectos adversos , Trastorno Depresivo Mayor/tratamiento farmacológico , Alucinógenos/efectos adversos , Atención Primaria de Salud , Psilocibina/efectos adversos , Ensayos Clínicos como Asunto
9.
Eur Neurol ; 2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38880096

RESUMEN

BACKGROUND: Mechanical thrombectomy represents a mainstay of management for acute ischemic stroke in the setting of large vessel occlusion. However, there are no clinical practice guidelines defining the role of thrombectomy at the extremes of age. In this scoping review, we aimed to summarize the existing medical and neurosurgical literature pertaining to mechanical thrombectomy in nonagenarians. The PubMed database was queried using the following terms and relevant citations assessed: "thrombectomy nonagenarian," "thrombectomy age 90," "stroke nonagenarian," and "ischemic stroke thrombectomy." Common measurable outcomes, including mortality, modified Rankin scale (mRS) score, and Thrombolysis in Cerebral Infarction (TICI) scale score, were utilized to compare results. SUMMARY: Thrombectomy was shown to improve functional outcomes in all eight of the studies included in the analysis. Mortality was assessed in only two reported studies, and thrombectomy was shown to provide a mortality benefit in one study amongst patients for whom first-pass reperfusion was achieved. Other outcomes of reported interest included greater early neurologic recovery at discharge and improved functional outcomes at 90 days amongst nonagenarians who underwent thrombectomy as compared to those who received thrombolytic therapy alone. Nonagenarians with good functional status at baseline were the most likely to have favorable outcomes. KEY MESSAGES: Mechanical thrombectomy improves outcomes among nonagenarians presenting with acute ischemic stroke due to large vessel occlusion. Further large-scale prospective studies are warranted to optimize patient selection and develop clinical practice guidelines specific to this important patient demographic.

10.
J Surg Oncol ; 127(1): 109-118, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36112396

RESUMEN

BACKGROUND AND OBJECTIVES: Colorectal cancer (CRC) sidedness is recognized as a prognostic factor for survival; left-sided colorectal cancer is associated with better outcomes than right-sided colon cancer (RsCC). We aimed to evaluate the influence of obesity on CRC sidedness and determine how race, age, and sex affect mortality among overweight and obese individuals. METHODS: A survey-weighted analysis was conducted using data obtained from the National Inpatient Sample between 2016 and 2019. RESULTS: Of the 24 549 patients with a diagnosis of CRC and a reported body mass index (BMI), 13.6% were overweight and 49.9% were obese. The race distribution was predominantly non-Hispanic Whites (69.7%), followed by Black (15.6%), Hispanic (8.7%), and other race (6.1%). Overweight (BMI: 25-29.9) and obese (BMI: ≥30) individuals were more likely to have RsCC (adjusted OR [aOR] = 1.28; 95% CI: 1.17-1.39, p < 0.001 and aOR = 1.45; 95% CI: 1.37-1.54, p < 0.001, respectively). Obese Black individuals were more likely to have RsCC as compared to their White counterparts (aOR = 1.23; 95% CI: 1.09-1.38). CONCLUSIONS: Obesity is associated with an increased risk of RsCC. In addition, racial disparities in CRC sidedness and outcomes are most pronounced among obese patients.


Asunto(s)
Neoplasias Colorrectales , Sobrepeso , Humanos , Femenino , Masculino , Sobrepeso/complicaciones , Estudios Transversales , Caracteres Sexuales , Obesidad/complicaciones
11.
Ann Surg Oncol ; 29(13): 8250-8260, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35978206

RESUMEN

BACKGROUND: Gastrointestinal extrapulmonary small cell carcinoma (GI EPSCCa) is a rare, aggressive neuroendocrine tumor. Factors affecting survival, including the prognostic significance of primary tumor site, remain under investigation. METHODS: Data from the surveillance, epidemiology, and end results (SEER) program were extracted to identify patients diagnosed with GI EPSCCa between 2000 and 2018. Cox proportional hazard models were used to assess prognostic factors based on primary tumor site. RESULTS: A total of 1687 patients were included in the survival analysis. The distribution of the primary tumor location was as follows: 31.5% colorectum (CRC), 22.1% esophageal, 20.6% pancreatic, 13.3% hepatobiliary (HB), 10.6% stomach, and 1.8% small intestine (SI). Esophagogastric and SI EPSCCa were more common among Black individuals, whereas CRC, HB, and pancreatic EPSCCa were more common among White patients (p = 0.012). There were no racial differences in OS for GI EPSCCa. HB EPSCCa was associated with inferior OS compared with esophageal tumors (adjusted hazard ratio [aHR] 1.21, 95% confidence interval [CI] 1.00-1.46; p = 0.048), and SI EPSCCa was associated with prolonged survival compared with esophageal EPSCCa (aHR 0.76, 95% CI 0.48-1.20; p = 0.237) but did not reach statistical significance. Surgical intervention and a treatment period after 2006 were associated with superior OS. CONCLUSIONS: The prognosis for GI ESPCCa varies based on site. Chemotherapy, radiation, and surgical resection are associated with improved outcomes; however, the prognosis for patients with EPSCCa remains dismal. Prospective studies are needed to guide therapy for this aggressive tumor.


Asunto(s)
Carcinoma de Células Pequeñas , Humanos , Carcinoma de Células Pequeñas/terapia , Carcinoma de Células Pequeñas/patología , Pronóstico , Programa de VERF , Estudios Retrospectivos , Análisis de Supervivencia
12.
Ann Noninvasive Electrocardiol ; 26(4): e12833, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33742501

RESUMEN

BACKGROUND: Cardiovascular events have been reported in the setting of coronavirus disease-19 (COVID-19). It has been hypothesized that systemic inflammation may aggravate arrhythmias or trigger new-onset conduction abnormalities. However, the specific type and distribution of electrocardiographic disturbances in COVID-19 as well as their influence on mortality remain to be fully characterized. METHODS: Electrocardiograms (ECGs) were obtained from 186 COVID-19-positive patients at a large tertiary care hospital in Northern Nevada. The following arrhythmias were identified by cardiologists: sinus bradycardia, sinus tachycardia, atrial fibrillation (A-Fib), atrial flutter, multifocal atrial tachycardia (MAT), premature atrial contraction (PAC), premature ventricular contraction (PVC), atrioventricular block (AVB), and right bundle branch block (RBBB). The mean PR interval, QRS duration, and corrected QT interval were documented. Fisher's exact test was used to compare the ECG features of patients who died during the hospitalization with those who survived. The influence of ECG features on mortality was assessed with multivariable logistic regression analysis. RESULTS: A-Fib, atrial flutter, and ST-segment depression were predictive of mortality. In addition, the mean ventricular rate was higher among patients who died as compared to those who survived. The use of therapeutic anticoagulation was associated with reduced odds of death; however, this association did not reach statistical significance. CONCLUSION: The underlying pathogenesis of COVID-19-associated arrhythmias remains to be established, but we postulate that systemic inflammation and/or hypoxia may induce potentially lethal conduction abnormalities in affected individuals. Longitudinal studies are warranted to evaluate the risk factors, pathogenesis, and management of COVID-19-associated cardiac arrhythmias.


Asunto(s)
COVID-19/mortalidad , COVID-19/patología , Electrocardiografía/métodos , Cardiopatías/mortalidad , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Comorbilidad , Femenino , Mortalidad Hospitalaria , Humanos , Masculino , Persona de Mediana Edad , Nevada/epidemiología , Medición de Riesgo , SARS-CoV-2 , Adulto Joven
13.
J Med Virol ; 92(11): 2516-2522, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32436994

RESUMEN

BACKGROUND: Current evidence suggests an important role of the interleukin-6 (IL-6) pathway in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related cytokine release storm in severely ill coronavirus disease 2019 (COVID-19) patients. Inhibition of the IL-6 pathway with tocilizumab has been employed successfully in some of these patients but the data is mostly consistent of case reports and series. METHODS: We performed a systematic search of PubMed, Embase, and Medline from 22nd April 2020 and again on 27th April 2020 using the following search terms alone or in combination: "COVID-19," "coronavirus," "SARS-CoV-2," "COVID," "anti-interleukin-6 receptor antibodies," "anti-IL-6," "tocilizumab," "sarilumab," "siltuximab." We included studies that reported individual patient data. We extracted and analyzed individual level data on baseline characteristics, laboratory findings, and clinical outcomes. The primary endpoint was in-hospital mortality. Secondary endpoints included in-hospital complications, recovery rates, effect of patient characteristics on the primary outcome and changes in levels of inflammatory markers. RESULTS: Three hundred fifty-two records were identified through a systematic search, of which 10 studies met the inclusion criteria. A single study currently under review was also added. Eleven observational studies encompassing 29 patients were included in the present review. There were more males (24 [82.8%]), and hypertension was the most common comorbidity (16 [48.3%]). Over an average of 5.4 hospital days, the primary endpoint occurred in 6 (20.7%) patients. Among surviving patients, about 10% had worsened disease and 17% recovered. The most common complication was acute respiratory distress syndrome (8 [27.6%]). The IL-6 level was significantly higher after the initiation of tocilizumab with median (interquartile range) of 376.6 (148-900.6) pg/mL compared to the baseline of 71.1 (31.9-122.8) pg/mL (P = .002). Mean (standard deviation) levels of C-reactive protein (CRP) were significantly decreased following treatment 24.6 (26.9) mg/L compared to baseline 140.4 (77) mg/L (P < .0001). Baseline demographics were not significantly different among survivors and nonsurvivors by Fisher's exact test. CONCLUSION: In COVID-19 patients treated with tocilizumab, IL-6 levels are significantly elevated, which are supportive of cytokine storm. Following initiation of tocilizumab, there is elevation in the IL-6 levels and CRP levels dramatically decrease, suggesting an improvement in this hyperinflammatory state. Ongoing randomized control trials will allow for further evaluation of this promising therapy. IMPORTANCE: Recent data indicate that severe COVID-19 causes a cytokine release storm and is associated with worse clinical outcomes and IL-6 plays an important role. It is suggestive that anti-IL-6 results in the improvement of this hyperinflammatory state. However, to our knowledge, there is no individual patient data systematic review performed to summarize baseline characteristics and clinical outcomes of COVID-19 patients who received tocilizumab.


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , COVID-19/terapia , Mortalidad Hospitalaria , Interleucina-6/antagonistas & inhibidores , COVID-19/inmunología , Síndrome de Liberación de Citoquinas/inmunología , Síndrome de Liberación de Citoquinas/terapia , Femenino , Humanos , Interleucina-6/inmunología , Masculino , Estudios Observacionales como Asunto , Receptores de Interleucina-6/antagonistas & inhibidores , Índice de Severidad de la Enfermedad , Factores de Tiempo , Resultado del Tratamiento
14.
Cancer Control ; 27(1): 1073274820956615, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32951450

RESUMEN

BACKGROUND: Race, gender, insurance status, and income play important roles in predicting health care outcomes. However, the impact of these factors has yet to be fully elucidated in the setting of hepatocellular carcinoma (HCC). METHODS: We designed a retrospective cohort study utilizing data from the Surveillance, Epidemiology, and End Results (SEER) program to identify patients diagnosed with resectable HCC (N = 28,518). Demographic factors of interest included race (Asian/Pacific Islander [API], African American [AA], Native American/Alaska Native [NA], or White [WH]) and gender (male [M] or female [F]). Insurance classifications included those having Medicare/Private Insurance [ME/PI], Medicaid [MAID], or No Insurance [NI]. Median household income was estimated for all diagnosed with HCC. Endpoints included: (1) overall survival; (2) likelihood of receiving a recommendation for surgery; and (3) specific surgical intervention performed. Multivariate multinomial logistic regression for relative risk ratio (RRR) and Cox regression models were used to identify pertinent associations. RESULTS: Race, gender, insurance status, and income had statistically significant effects on the likelihood of surgical recommendation and overall survival. API were more likely to receive a recommendation for hepatic resection (RRR = 1.45; 95% CI: 1.31-1.61; Reference Race: AA) and exhibited prolonged overall survival (HR = 0.77; 95% CI: 0.73-0.82; Reference Race: AA) as compared to members of any other ethnic group; there was no difference in these endpoints between AA, NA, or WH individuals. Gender also had a significant effect on survival: Females exhibited superior overall survival (HR = 0.89; 95% CI: 0.85-0.93; Reference Gender: M) as compared to males. Patients who had ME/PI were more likely than those with MAID or NI to receive a surgical recommendation. ME/PI was also associated with superior overall survival. Conclusions: Race, gender, insurance status, and income have measurable effects on HCC management and outcomes. The underlying causes of these disparities warrant further investigation.


Asunto(s)
Carcinoma Hepatocelular/mortalidad , Etnicidad/estadística & datos numéricos , Hepatectomía/mortalidad , Seguro de Salud , Neoplasias Hepáticas/mortalidad , Factores Socioeconómicos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Hepatocelular/economía , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/cirugía , Femenino , Estudios de Seguimiento , Hepatectomía/economía , Humanos , Neoplasias Hepáticas/economía , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Programa de VERF , Tasa de Supervivencia , Adulto Joven
15.
Thromb J ; 18(1): 30, 2020 Oct 29.
Artículo en Inglés | MEDLINE | ID: mdl-33292273

RESUMEN

BACKGROUND: Hypertensive disorders of pregnancy are associated with vascular complications, including ischemic stroke and cervical artery dissection. Vertebral artery dissection (VAD), however, is rare. We describe a 31-year-old female who presented with vertigo, nausea, and vomiting and was found to have a VAD. In addition, we discuss the presentation, differential diagnosis, and pathogenesis of this uncommon but clinically significant vascular event and summarize other cases of vertebral artery dissection described in the medical literature. CASE PRESENTATION: A 31-year-old Hispanic woman presented 10 days postpartum with a one-day history of vertigo, nausea, vomiting, and frontal headache. The patient's pregnancy course had been complicated by preeclampsia, chorioamnionitis, and iron-deficiency anemia, and her delivery was complicated by acute hemorrhage. Physical examination was significant for left leg ataxia. Laboratory studies showed marked thrombocytosis. Emergent computed tomography (CT) scan of the head was obtained and revealed a left cerebellar ischemic large vessel stroke. Subsequent CT angiography of the head and neck showed a left VAD. Based on correlation of the clinical history and laboratory and imaging findings, a diagnosis of vertebral artery dissection secondary to reactive (secondary) thrombocytosis from overlapping iron-deficiency anemia and acute hemorrhage was established. The patient was started on a heparin infusion and experienced significant improvement after a four-day hospitalization. CONCLUSION: VAD is a rare but important cause of neurologic symptoms in the postpartum period and should be considered in the differential diagnosis for women who present with headache and/or vertigo. Women aged 30 years or older and those with a history of a hypertensive disorder of pregnancy are at particularly high risk. Prompt diagnosis and management of VAD is essential to ensure favorable outcomes.

16.
J Surg Oncol ; 120(2): 270-279, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31102468

RESUMEN

BACKGROUND AND OBJECTIVES: Conflicting evidence indicates that both race and geographic setting may influence the management of malignancies such as gastric adenocarcinoma (GAC). METHODS: We designed a retrospective cohort study utilizing data from the Surveillance, Epidemiology, and End Results program to identify patients with resectable GAC (N = 15 991). Exposures of interest were race and geographic region of diagnosis (West [WE], Midwest [MW], South [SO], or Northeast [NE]). Endpoints included: (1) recommendation against surgery and (2) gastric adenocarcinoma-specific survival (GACSS). Multivariable logistic and Cox regression models were used to identify pertinent associations. RESULTS: A total of 15 991 patients were included (2007-2015). In adjusted analysis, African American individuals more frequently received a recommendation against surgical resection than White (adjusted odds ratio [aOR] = 0.86; 95% confidence interval [CI], 0.76-0.98), Asian American (aOR = 0.55; 95% CI, 0.46-0.65), and American Indian (aOR = 0.50; 95% CI, 0.31-0.82) individuals. In addition to race-based discrepancies, there was a significant association between geography and management: individuals diagnosed with GAC in the SO were more likely to receive a recommendation against surgery (odds ratio = 1.35; 95% CI, 1.23-1.49) and exhibited poorer GACSS as compared with those in the WE, MW, or NE regions. CONCLUSIONS: Race and geographic region of diagnosis affect treatment recommendations and GACSS among individuals with resectable tumors. African Americans with resectable cancers are more likely to receive a recommendation against surgery than individuals of other racial groups.


Asunto(s)
Adenocarcinoma/etnología , Adenocarcinoma/terapia , Etnicidad/estadística & datos numéricos , Neoplasias Gástricas/etnología , Neoplasias Gástricas/terapia , Población Blanca/estadística & datos numéricos , Adenocarcinoma/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Programa de VERF , Factores Socioeconómicos , Neoplasias Gástricas/mortalidad , Estados Unidos , Adulto Joven
20.
Skinmed ; 15(5): 343-347, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-29139361

RESUMEN

Angiokeratomas are benign vascular lesions characterized by ectatic blood vessels in the papillary dermis with overlying acanthosis and hyperkeratosis, often occurring as idiopathic scrotal tumor and rarely as penile lesions. Twelve men, including our case of a 58-year-old white man, have been reported with angiokeratomas of the glans penis. The lesions typically present as asymptomatic dome-shaped papules ranging in size from 0.5 to 5 mm and present as red, purple, blue, or black lesions along the penile coronal rim. Histopathologic examination of the lesions reveals dilated, thin-walled vascular structures in the upper portion of the dermis with overlying acanthosis and/or hyperkeratosis. Such angiokeratomas may have a multifactorial etiology with elevations in local venous pressure, degeneration of elastic tissue, and/or capillary injury. Biopsy would exclude a melanocytic lesion, particularly melanoma. Laser surgery is an option for patients presenting with multiple lesions or lesions that coalesce to form a plaque.


Asunto(s)
Angioqueratoma/patología , Neoplasias del Pene/patología , Neoplasias Cutáneas/patología , Humanos , Masculino , Persona de Mediana Edad , Pene
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