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Patients with advanced cancer generate 4 million visits annually to emergency departments (EDs) and other dedicated, high-acuity oncology urgent care centers. Because of both the increasing complexity of systemic treatments overall and the higher rates of active therapy in the geriatric population, many patients experiencing acute decompensations are frail and acutely ill. This article comprehensively reviews the spectrum of oncologic emergencies and urgencies typically encountered in acute care settings. Presentation, underlying etiology, and up-to-date clinical pathways are discussed. Criteria for either a safe discharge to home or a transition of care to the inpatient oncology hospitalist team are emphasized. This review extends beyond familiar conditions such as febrile neutropenia, hypercalcemia, tumor lysis syndrome, malignant spinal cord compression, mechanical bowel obstruction, and breakthrough pain crises to include a broader spectrum of topics encompassing the syndrome of inappropriate antidiuretic hormone secretion, venous thromboembolism and malignant effusions, as well as chemotherapy-induced mucositis, cardiomyopathy, nausea, vomiting, and diarrhea. Emergent and urgent complications associated with targeted therapeutics, including small molecules, naked and drug-conjugated monoclonal antibodies, as well as immune checkpoint inhibitors and chimeric antigen receptor T-cells, are summarized. Finally, strategies for facilitating same-day direct admission to hospice from the ED are discussed. This article not only can serve as a point-of-care reference for the ED physician but also can assist outpatient oncologists as well as inpatient hospitalists in coordinating care around the ED visit.
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Hipercalcemia , Neoplasias , Anciano , Humanos , Urgencias Médicas , Oncología Médica , Neoplasias/complicaciones , Neoplasias/terapia , Náusea , Hipercalcemia/etiologíaRESUMEN
BACKGROUND: The opioid overdose crisis is one of the worst public health crises ever to face the US and emerging evidence suggests its effects are compounded by the presence of drug adulterants. Here we report our efforts to characterize the adulterants present within the local fentanyl supply of San Diego County, obtained from undifferentiated drug samples seized by local law enforcement over the calendar year 2021. METHODS: Thirty-two participating local law enforcement agencies across San Diego submitted 4838 unknown individual illicit drug samples (total of 312 kg) to the San Diego County Sheriff's Department Regional Crime Laboratory for identification. RESULTS: Qualitative analysis of these samples via FTIR and GC-MS identified methamphetamine (38.7%), fentanyl (20.8%), diacetylmorphine (heroin) (10.2%), codeine (5.8%) and alprazolam (4.3%) as the most common illicit substances and the presence of 52 unique adulterants. The most common adulterants included 4-methylaminoantipyrine (4-MAAP) (10.9%), mannitol (9%), acetaminophen (8.5%), methamphetamine (4.2%), diacetylmorphine (heroin) (3.6%), tramadol (1.9%), and xylazine (1.7%). Several additional pharmacologically active adulterants and contaminants of interest were also identified. CONCLUSION: This analysis is vital for public health use and harm reduction efforts at the level of the individual consumer. Continued direct surveillance of the drug supply is necessary for the detection of potentially harmful adulterants that may pose serious threats to the public.
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Sobredosis de Droga , Drogas Ilícitas , Metanfetamina , Humanos , Fentanilo/análisis , Heroína , Aplicación de la Ley , Contaminación de Medicamentos , Analgésicos OpioidesRESUMEN
BACKGROUND: Opioid overdose is a major cause of mortality in the United States. In spite of efforts to increase naloxone availability, distribution to high-risk populations remains a challenge. OBJECTIVE: To assess the effects of multiple different naloxone distribution methods on patient obtainment of naloxone in the emergency department (ED) setting. METHODS: Naloxone was provided to patients in three 12-month phases between February 2020 and February 2023. In Phase 1, physicians could offer patients electronic prescriptions, which were filled in a nearby in-hospital discharge pharmacy. In Phase 2, physicians directly provided patients with take-home naloxone at discharge. In Phase 3, distribution was expanded to allow ED staff to hand patients take-home naloxone at time of discharge. The total number of prescriptions, rate of prescription filling, and amount of take-home naloxone kits provided to patients were then statistically analyzed using 95% confidence intervals (CI) and chi-squared testing. RESULTS: In Phase 1, 348 naloxone prescriptions were written, with 133 (95% CI 112.5-153.5) filled. In Phase 2, 327 (95% CI 245.5-408.5) take-home naloxone kits were given to patients by physicians. In Phase 3, 677 (95% CI 509.5-844.5) take-home naloxone kits were provided to patients by ED staff. There were statistically significant increases in naloxone distribution from Phase 1 to Phase 2, and Phase 2 to Phase 3. CONCLUSIONS: Take-home naloxone increases access when compared with naloxone prescriptions in the ED setting. A multidisciplinary approach combined with the removal of regulatory and administrative barriers allowed for further increased distribution of no-cost naloxone to patients.
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Sobredosis de Droga , Trastornos Relacionados con Opioides , Farmacia , Humanos , Estados Unidos , Naloxona/uso terapéutico , Antagonistas de Narcóticos/uso terapéutico , Trastornos Relacionados con Opioides/tratamiento farmacológico , Sobredosis de Droga/tratamiento farmacológico , Servicio de Urgencia en Hospital , Analgésicos Opioides/uso terapéuticoRESUMEN
Hand warmer packets are common products used to provide a portable, nonflammable heat source via the exothermic oxidation of iron. We present the first reported case of pediatric hand warmer packet ingestion in a three-year-old male who developed an elevated serum iron concentration (peak 335â ug/dL) and gastrointestinal injury after ingesting the contents of a HOTHANDS hand warmer packet. He was treated with endoscopic gastric foreign body removal and lavage, as well as proton-pump inhibitors and whole bowel irrigation. Hand warmer packs contain reduced elemental iron powder, which has been shown to have a more favorable safety profile when compared to iron salts. The mechanism of toxicity for reduced iron is unknown, though it is thought to be due to conversion to more toxic iron ions in an acidic environment. While the current adult literature suggests that ingestion of a single hand warmer packet is without significant risk, our case demonstrates that even a partial ingestion carries a significant risk of both iron toxicity and direct gastrointestinal caustic injury in a young child. This case demonstrates the need for multidisciplinary care and consideration of urgent endoscopic foreign body removal and gastric lavage followed by whole bowel irrigation to mitigate the potential of severe iron toxicity.
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Traumatismos Abdominales , Cuerpos Extraños , Traumatismos Torácicos , Preescolar , Humanos , Masculino , Ingestión de Alimentos , Cuerpos Extraños/terapia , Mano , Hierro , Extremidad SuperiorRESUMEN
The Southern Pacific rattlesnake (Crotalus helleri) is commonly encountered throughout Southern California. Typical toxicity includes tissue injury and hematologic toxicity. However, neurotoxicity is not commonly reported with rattlesnake envenomations, other than infrequently with select species, including the Mojave rattlesnake (Crotalus scutulatus scutulatus). Importantly, clinical neurotoxicity has not been well described with the Southern Pacific rattlesnake, the only rattlesnake in the city of Los Angeles, along with the Southern and coastal regions of Los Angeles County. In this case series, 7 patients envenomated by the Southern Pacific rattlesnake with significant neurotoxicity, including dysarthria, ataxia, and myokymia, are presented. Clinicians practicing in this region should be aware of evolving patterns of toxicity associated with the Southern Pacific rattlesnake.
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Venenos de Crotálidos , Mordeduras de Serpientes , Animales , Humanos , CrotalusRESUMEN
A 48-year-old male intentionally ingested "gopher killer" containing strychnine as a, suicide attempt. He rapidly developed generalized muscle spasms with opisthotonos followed by cardiovascular collapse. He was resuscitated, treated with 24 h of, neuromuscular paralysis, and was discharged on hospital day 10 without sequelae. A blood strychnine concentration obtained five hours post ingestion was 2.2 mg/L. Strychnine poisoning is exceedingly rare in the modern United States and this report contains a video recording of the classic exam findings.
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Intoxicación , Estricnina , Masculino , Humanos , Estados Unidos , Persona de Mediana Edad , Espasmo , Intento de Suicidio , Progresión de la Enfermedad , Intoxicación/terapiaRESUMEN
Human exposures to "fire color changing" agents containing copper salts (CS) are rare. We report the case of an intentional mixed CS ingestion with resulting corrosive gastrointestinal injury absent classic laboratory abnormalities. A 23-year-old male with a history of bipolar disorder presented to the emergency department two hours after intentional ingesting an unknown quantity of the fire colorant "Mystical Fire," which contains cupric sulfate (CuSO4) and cupric chloride (CuCl2). He subsequently developed nausea and abdominal pain and had several episodes of vomiting. Physical examination was notable for diffuse abdominal tenderness without peritoneal signs. Laboratory evaluation was without signs of hemolysis, metabolic derangements, or acute kidney or liver injury. He was noted to have a methemoglobin concentration of 2.2%, which did not require treatment. Serum copper testing was within normal limits. Abdominal CT imaging showed no significant findings. Endoscopy was performed and revealed diffuse esophagitis and gastritis. The patient was started on a proton pump inhibitor and discharged. In this case, the absence of classic laboratory findings of copper did not rule out the presence of gastrointestinal injury. Further investigation is needed to determine the most effective means of ruling out clinically significant CS ingestions.
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Cáusticos , Masculino , Humanos , Adulto Joven , Adulto , Sales (Química) , Cobre , Endoscopía Gastrointestinal , Ingestión de AlimentosRESUMEN
BACKGROUND: The Komodo dragon (Varanus komodoensis) is the world's largest living lizard and exists in private captivity worldwide. Bites to humans are rare and have been proposed to be both infectious and venomous. CASE REPORT: A 43-year-old zookeeper was bitten on the leg by a Komodo dragon and suffered local tissue damage with no excessive bleeding or systemic symptoms to suggest envenomation. No specific therapy was administered other than local wound irrigation. The patient was placed on prophylactic antibiotics and on follow-up, which revealed no local or systemic infections, and no other systemic complaints. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Although venomous lizard bites are uncommon, prompt recognition of possible envenomation and management of these bites is important. Komodo dragon bites may produce not only superficial lacerations but also deep tissue injury, but are unlikely to produce serious systemic effects; whereas Gila monster and beaded lizard bites may cause delayed angioedema, hypotension, and other systemic symptoms. Treatment in all cases is supportive.
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Mordeduras y Picaduras , Lagartos , Animales , Humanos , AdultoRESUMEN
OBJECTIVES: Lithium is an uncommon pediatric exposure, and the effects of accidental or exploratory ingestions are not well characterized. This study examined the clinical effects and outcomes of unintentional lithium ingestions treated in a health care facility for patients up to 16 years old. METHODS: The database from a single-state Poison Control System was queried for all pediatric lithium exposures managed in a health care facility between January 2006 and December 2021. Inclusion criteria were 16 years or younger and acute lithium exposure treated in a health care facility. Those older than 16 years, nonoral exposures, intentional, chronic, or nonlithium exposures, and out-of-state patients were excluded. RESULTS: One hundred eighteen cases were included, and 619 were excluded. The median age was 2 years (range, 0.5-15 years). One hundred fifteen (97%) were 7 years or younger. Sixty-eight (57.6%) were boys. One hundred thirteen (96%) were exploratory ingestions. Lithium carbonate was the most common formulation, with a median reported dose of 525 mg (range, 100-13,500 mg). Sixty-seven (57%) had serum lithium concentrations available: 19 (28%) were detectable (>0.1 mEq/L) and 4 were supratherapeutic (>1.2 mEq/L).One hundred (85%) patients were coded as having no effects. Four (3%) patients had coded effects-1 mild, 2 moderate, and 1 major; all were polydrug ingestions and recovered fully with basic supportive care. The loss to follow-up rate was 12%.A small minority received treatment with intravenous fluids and/or whole bowel irrigation. Thirteen (11%) were admitted, 3 to the ICU. No morbidity or mortality was reported. CONCLUSIONS: The majority of unintentional pediatric lithium ingestions examined were exploratory and resulted in no significant symptoms. Only a small minority had detectable serum lithium concentrations. All isolated lithium exposures were asymptomatic. Unintentional exposures appear to be benign, even with detectable lithium levels. Further study is needed to better risk stratify for home care versus health care facility evaluation.
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Litio , Centros de Control de Intoxicaciones , Masculino , Niño , Humanos , Lactante , Preescolar , Adolescente , Femenino , Estudios Retrospectivos , AccidentesRESUMEN
OBJECTIVES: Rattlesnake envenomations are uncommon, and the majority occur in adults. Although Crotalidae equine immune F(ab') 2 antivenom (F(ab') 2 AV; trade name ANAVIP) was introduced in 2018, no pediatric specific studies of F(ab') 2 AV have been reported to date. The objective of this study was to evaluate the clinical performance and adverse effects of F(ab') 2 AV in children. METHODS: A single-center, retrospective chart review was performed on patients with rattlesnake envenomation presenting to a children's hospital between October 2018 and August 2022. Inclusion criteria were age younger than 18 years and F(ab') 2 AV use. Exclusion criteria were other antivenom use at any time and presentation beyond 24 hours postenvenomation.Demographic characteristics, hemoglobin, platelet count, fibrinogen, international normalized ratio, number of F(ab') 2 AV vials used, infusion-related complications, and clinical outcomes were collected. RESULTS: Twenty-six patients, 19 males and 7 females, with a mean age of 7.7 years (0.67 to 16 years) met inclusion criteria. Fourteen (54%) were treated with only the initial 10 vial F(ab') 2 AV doses. Twelve patients were given additional doses with a median additional vials of 10 (4-34 vials; interquartile range, 8.75-12 vials). The median total vials given for all patients was 10 (10-44 vials; interquartile range, 10-20 vials).Two patients developed acute infusion reactions. Both were treated by slowing the infusion rate and with medications (diphenhydramine, corticosteroids). No delayed reactions were noted. No patients required blood products or surgical interventions.After discharge, no complications, recurrent symptoms, return visits, or readmissions were reported. Follow-up by chart review or phone was obtained for 18 patients, and no postdischarge complications were noted. Seven patients had postdischarge hematologic laboratory evaluations and all were normal. CONCLUSIONS: Although limited by small sample size and postdischarge follow-up, F(ab') 2 AV was well tolerated in our series of pediatric patients, consistent with prior studies of all age groups.
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Mordeduras de Serpientes , Adulto , Masculino , Femenino , Humanos , Niño , Animales , Caballos , Adolescente , Mordeduras de Serpientes/tratamiento farmacológico , Mordeduras de Serpientes/complicaciones , Antivenenos/efectos adversos , Estudios Retrospectivos , Cuidados Posteriores , Fragmentos Fab de Inmunoglobulinas/uso terapéutico , Alta del PacienteRESUMEN
Dextromethorphan polistirex is an extended-release formulation of dextromethorphan hydrobromide, marketed as Delsym® (Reckitt; Parsippany, NJ), with a duration of action roughly two to three times that of the standard formulation. The polistirex binder is responsible for the prolonged duration of action by slowing the release of active ingredient; the liberated dextromethorphan has unchanged pharmacokinetics and clinical effects. A 23-month-old male presented following a 900 mg (71.4 mg/kg) dextromethorphan polistirex ingestion 90 min prior. On arrival, he was unresponsive, tachycardic, and hypertensive with mydriasis, roving eye movements, rotary nystagmus, and opisthotonos. Approximately 90 min after arrival, he required intubation for airway protection. The blood dextromethorphan concentration from 75 min after arrival was 110 ng/mL (10-40 ng/ml therapeutic). He was extubated approximately 13 h after arrival and discharged that day. Most pediatric dextromethorphan overdoses produce mild symptoms that are not considered to be life-threatening. Life threatening overdoses are rare. The toxic dextromethorphan dose and blood concentration as well as the toxicokinetics of the polistirex formulation are not well defined. Our case suggests that a blood dextromethorphan concentration exceeding 100 ng/mL can be toxic in this age group, however further study is needed.
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Sobredosis de Droga , Nistagmo Patológico , Humanos , Niño , Masculino , Lactante , Preescolar , Dextrometorfano , Excipientes , Preparaciones de Acción RetardadaRESUMEN
BACKGROUND: Diethylene glycol (DEG) is an industrial solvent with many uses, including brake fluids. It has also caused mass poisonings after use as an inappropriate substitute for propylene glycol or glycerin, though individual ingestions are rare. Like other toxic alcohols, DEG is metabolized by alcohol dehydrogenase and aldehyde dehydrogenase, with toxicity likely mediated by the resulting metabolites. Fomepizole, an alcohol dehydrogenase inhibitor, is used to prevent metabolite formation with other toxic alcohol exposures. Fomepizole is recommended for DEG poisoning, though supporting clinical evidence is limited. CASE REPORT: A 31-year-old man presented after ingestion of DEG-containing brake fluid and hydrocarbon-containing "octane booster." He was noted to be clinically intoxicated, with a mildly elevated anion gap metabolic acidosis and no osmolar gap. DEG level was later found to be elevated, consistent with his ingestion. He was treated with fomepizole alone, with resolution of metabolic acidosis and clinical findings over the next 2 days. No delayed neurologic sequelae were present at 52-day follow-up. Our case provides additional evidence supporting the use of fomepizole for DEG poisoning. Consistent with other toxic alcohols, DEG poisoning, especially early presentations, may benefit from empiric fomepizole administration. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: DEG poisoning is potentially life threatening, but treatable if identified early. An ingestion can be toxic despite a normal osmolar gap, leading to false reassurance. Finally, it is rare, so emergency physicians must be made aware of its potential dangers.
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Acidosis , Intoxicación , Acidosis/inducido químicamente , Acidosis/tratamiento farmacológico , Adulto , Alcohol Deshidrogenasa/uso terapéutico , Aldehído Deshidrogenasa/uso terapéutico , Antídotos/farmacología , Antídotos/uso terapéutico , Ingestión de Alimentos , Glicol de Etileno , Glicoles de Etileno , Fomepizol/uso terapéutico , Glicerol/uso terapéutico , Humanos , Masculino , Octanos/uso terapéutico , Intoxicación/terapia , Glicoles de Propileno/uso terapéutico , Pirazoles/farmacología , Pirazoles/uso terapéutico , Solventes/uso terapéuticoRESUMEN
INTRODUCTION: Prolactinomas are the most common functional pituitary adenomas. Current classification systems rely on phenotypic elements and have few molecular markers for complementary classification. Treatment protocols for prolactinomas are also devoid of molecular targets, leaving those refractory to standard treatments without many options. METHODS: A systematic literature review was performed utilizing the PRISMA guidelines. We aimed to summarize prior research exploring gene and protein expression in prolactinomas in order to highlight molecular variations associated with tumor development, growth, and prolactin secretion. A PubMed search of select MeSH terms was performed to identify all studies reporting gene and protein expression findings in prolactinomas from 1990 to 2014. RESULTS: 1392 abstracts were screened and 51 manuscripts were included in the analysis, yielding 54 upregulated and 95 downregulated genes measured by various direct and indirect analytical methods. Of the many genes identified, three upregulated (HMGA2, HST, SNAP25), and three downregulated (UGT2B7, Let7, miR-493) genes were selected for further analysis based on our subjective identification of strong potential targets. CONCLUSIONS: Many significant genes have been identified and validated in prolactinomas and most have not been fully analyzed for therapeutic and diagnostic potential. These genes could become candidate molecular targets for biomarker development and precision drug targeting as well as catalyze deeper research efforts utilizing next generation profiling/sequencing techniques, particularly genome scale expression and epigenomic analyses.
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Regulación Neoplásica de la Expresión Génica , Neoplasias Hipofisarias/metabolismo , Prolactinoma/metabolismo , Humanos , Neoplasias Hipofisarias/genética , Prolactinoma/genéticaRESUMEN
Ectopic pituitary adenomas are exceedingly rare entities that are often misdiagnosed. The resulting delay in diagnosis may be particularly concerning in the case of Cushing syndrome caused by an ectopic adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma. Although the total resection of ectopic adenomas results in rapid and durable remission, persistent Cushing syndrome is often associated with permanently damaging invasive procedures and significantly higher risk of mortality. The authors report the case of a 48-year-old man with ACTH-dependent Cushing syndrome. On the morning before surgery, his serum cortisol measured 51 µg/dl, his ACTH level was 195.7 pg/ml, and his urinary free cortisol level was 2109 µg/day. Serum cortisol was not suppressed with the administration of high-dose dexamethasone. Imaging showed separate masses in both the sphenoid sinus and the pituitary gland, complicating the diagnostic process and requiring pathological assessment of both masses. No other abnormalities were found on thoracic, abdominal, or pelvic scans. Gross-total resection of both lesions was accomplished via an endoscopic endonasal transsphenoidal approach. Pathology confirmed an ectopic ACTH pituitary adenoma of the sphenoid sinus and a Crooke hyaline change of the pituitary gland. The patient achieved stable hormonal remission without significant postoperative complications, returned to full activity within 3 months, and remained disease free nearly 1 year after tumor resection. In a systematic literature review, the authors identified 41 cases of ectopic ACTH-secreting pituitary adenomas, including 18 arising in the sphenoid sinus without direct involvement of the sella. Including the case described here, the total number of ectopic ACTH pituitary adenomas arising in the sphenoid sinus was 19, and the total number of ectopic ACTH pituitary adenomas without regard to location was 42. For the 19 patients with adenomas found in the sphenoid sinus, ages ranged from 16 to 76 years, and there were 15 women and 4 men. The mean and median diameters of the resected sphenoid masses were 13.9 and 8 mm, respectively, with a range of 3-55 mm. Seven were microadenomas (< 1 cm). Fifteen of the 19 cases reported serum ACTH and morning cortisol levels, the means of which were 106.7 pg/ml and 32.5 µg/dl, respectively. Gross-total tumor resection was achieved in all patients except one, and in all of them durable hormonal remission of Cushing syndrome was achieved (mean follow-up time 20 months). Ectopic pituitary adenomas are rare but important causes of Cushing syndrome and related endocrinopathies, particularly because of the rapid onset and severity of symptoms with atypical presentation. Ectopic pituitary adenomas, especially those in the nasal cavity, nasopharynx, or paranasal sinuses, are easily misidentified. Any patient presenting with signs and symptoms of Cushing syndrome without any obvious pituitary adenoma or other sources of hypercortisolemia should be thoroughly screened for an ectopic adenoma. However, as with the case presented here, the coincident existence of a sellar mass should not preclude the possibility of an ectopic source. There should be a high degree of clinical suspicion for any mass in the general area surrounding the sella when evaluating Cushing syndrome.
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Adenoma Hipofisario Secretor de ACTH/diagnóstico , Adenoma Hipofisario Secretor de ACTH/cirugía , Adenoma/diagnóstico , Adenoma/cirugía , Endoscopía , Cavidad Nasal/cirugía , Seno Esfenoidal/cirugía , Adolescente , Adulto , Anciano , Endoscopía/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Seno Esfenoidal/patología , Adulto JovenRESUMEN
OBJECT Functional corticotroph pituitary adenomas (PAs) secrete adrenocorticotropic hormone (ACTH) and are the cause of Cushing's disease, which accounts for 70% of all cases of Cushing's syndrome. Current classification systems for PAs rely primarily on laboratory hormone findings, tumor size and morphology, invasiveness, and immunohistochemical findings. Likewise, drug development for functional ACTH-secreting PAs (ACTH-PAs) is limited and has focused largely on blocking the production or downstream effects of excess cortisol. The authors aimed to summarize the findings from previous studies that explored gene and protein expression of ACTH-PAs to prioritize potential genetic and protein targets for improved molecular diagnosis and treatment of Cushing's disease. METHODS A systematic literature review was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A PubMed search of select medical subject heading (MeSH) terms was performed to identify all studies that reported gene- and protein-expression findings in ACTH-PAs from January 1, 1990, to August 24, 2014, the day the search was performed. The inclusion criteria were studies on functional ACTH-PAs compared with normal pituitary glands, on human PA tissue only, with any method of analysis, and published in the English language. Studies using anything other than resected PA tissue, those that compared other adenoma types, those without baseline expression data, or those in which any pretreatment was delivered before analysis were excluded. RESULTS The primary search returned 1371 abstracts, of which 307 were found to be relevant. Of those, 178 were selected for secondary full-text analysis. Of these, 64 articles met the inclusion criteria and an additional 4 studies were identified from outside the search for a total of 68 included studies. Compared with the normal pituitary gland, significant gene overexpression in 43 genes and 22 proteins was reported, and gene underexpression in 58 genes and 15 proteins was reported. Immunohistochemistry was used in 39 of the studies, and reverse transcriptase polymerase chain reaction was used in 26 of the studies, primarily, and as validation for 4 others. Thirteen studies used both immunohistochemistry and reverse transcriptase polymerase chain reaction. Other methods used included microarray, in situ hybridization, Northern blot analysis, and Western blot analysis. Expression of prioritized genes emphasized in multiple studies were often validated on both the gene and protein levels. Genes/proteins found to be overexpressed in ACTH-PAs relative to the normal pituitary gland included hPTTG1/securin, NEUROD1/NeuroD1 (Beta2), HSD11B2/11ß-hydroxysteroid dehydrogenase 2, AKT/Akt, protein kinase B, and CCND1/cyclin D1. Candidate genes/proteins found to be underexpressed in ACTH-PAs relative to the normal pituitary gland included CDKN1B/p27(Kip1), CDKN2A/p16, KISS1/kisspeptin, ACTHR/ACTH-R, and miR-493. CONCLUSIONS On the basis of the authors' systematic review, many significant gene and protein targets that may contribute to tumorigenesis, invasion, and hormone production/secretion of ACTH have been identified and validated in ACTH-PAs. Many of these potential targets have not been fully analyzed for their therapeutic and diagnostic potential but may represent candidate molecular targets for biomarker development and drug targeting. This review may help catalyze additional research efforts using modern profiling and sequencing techniques and alteration of gene expression.
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Adenoma Hipofisario Secretor de ACTH/genética , Adenoma Hipofisario Secretor de ACTH/metabolismo , Adenoma/genética , Adenoma/metabolismo , Regulación Neoplásica de la Expresión Génica , Humanos , Kisspeptinas/biosíntesis , Securina/biosíntesisRESUMEN
Phenobarbital is a long-acting barbiturate used to treat alcohol withdrawal and epilepsy. Acute overdoses present with varying levels of central nervous system depression and large overdoses can be life threatening. Phenobarbital is an attractive candidate for enhanced elimination using urinary alkalinization given it is a weak acid with a long half-life and extensive urinary elimination. Limited human data exist regarding use of urine alkalinization for the treatment of phenobarbital overdose. We present a fourteen-year-old female who was treated with urinary alkalinization alone following an intentional ingestion of 3800â¯mg (84.4â¯mg/kg) of phenobarbital tablets. Urine drugs of abuse screening was preliminary positive for barbiturates and confirmed to be phenobarbital only. The initial serum phenobarbital concentration, drawn nine hours post-ingestion, was 97.4â¯mcg/ml (normal range 15-40â¯mcg/ml). Urinary alkalinization with sodium bicarbonate was started approximately 12â¯h post-ingestion and stopped at 72â¯h post-ingestion; clinical toxicity resolved by hospital day 5. The infusion was titrated to a urinary pH of greater than 7.5. Serial serum and urine phenobarbital measurements were obtained to determine elimination half-life and urinary excretion. The elimination half-life while undergoing urinary alkalinization was 81.3â¯h. Prior to initiation of urinary alkalinization, the urine phenobarbital concentration was 37â¯mcg/ml. Approximately 8.75â¯h after initiation, it was greater than 200â¯mcg/ml at a urine pH of 8.5. Urinary alkalinization appeared to augment urinary phenobarbital excretion, though with no discernible effect on elimination half-life and unclear clinical benefit. Further research is needed to better characterize the clinical effects of urinary alkalinization for phenobarbital overdose.
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Ethanol remains one of the most frequently abused agents by adolescents, exceeding all others except for vaping nicotine, and use is rising. With increased ethanol use comes a greater risk for dependence and potential for alcohol withdrawal syndromes (AWS). Pediatric AWS is extremely rare and poorly characterized in the literature. Pediatric acute care practitioners may have limited exposure to AWS. We report the case of a 16-year-old male with a history of polysubstance abuse who presented with mild AWS and progressed rapidly to delirium tremens. His withdrawal was initially refractory to high dose benzodiazepine therapy but responded well to phenobarbital. This case highlights how rapidly and dangerously AWS can progress if not aggressively treated. Given the rise in adolescent alcohol use and potential for life threatening symptoms, practitioners, especially in acute care specialties such as emergency medicine, critical care, and hospital medicine, would benefit from additional familiarity with AWS diagnoses and management strategies.
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Lithium induced cardiotoxicity is associated with several electrocardiographic (ECG) findings. The most commonly observed cardiac effects include QT prolongation, Twave abnormalities, and to lesser extent SA node dysfunction and ventricular arrythmias. We present a case of a 13-year-old female with acute lithium overdose whodeveloped Mobitz I, a manifestation of lithium associated cardiotoxity not previously reported. The patient had no significant past medical history and presented to the emergency department 1 h after intentional overdose of 10 tablets of unknown drug. Parents reported that the patient had visited her grandmother, who "regularly took many different kinds of medications," earlier that same evening. On physical examination the patient had reassuring vital signs, was in no acute distress,cardiopulmonary examination was normal, had clear sensorium, and no evidence of a toxidrome. On serological examination complete blood count, chemistries panel, and liver function tests did not show significant derangements. 4 h post-ingestion acetaminophen concentration was 28 mcg/ml and below indication for n-acetylcysteine antidote therapy. During her ED course she showed evidence of Mobitz I (Wenckebach) on 12-lead ECG. No prior ECGs were available for comparison. Medical toxicology was consulted at that time given concern for potential cardiotoxicity from an unknown xenobiotic. Serum dioxin and lithium concentrations were subsequently requested. Serum digoxin concentration was undetectable. Serum lithium concentrations was 1.7 mEq/L (0.6-1.2 mEq/L therapeutic range). The patient was treated with intravenous hydration at twice maintenance rate. Repeat lithium concertation 14 h post-ingestion was undetectable. During her admission, the patient remained hemodynamically stable and asymptomatic despite occasional episodes of Mobitz I, lasting seconds to minutes. Repeat 12-lead ECG obtained 20 h post-ingestion showed normal sinus rhythm. Cardiology recommendations included ambulatory Holter monitoring upon discharge and follow-up in clinic within two weeks. The patient was medically cleared after 36 h of monitoring and discharged after psychiatric evaluation. Our case demonstrates that patients who develop a new Mobitz I atrioventricular block of unclear etiology in the setting of acute ingestion should be screened for lithium exposure, even if otherwise free of more typical manifestations of lithium toxicity.
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We report a rare domestic case of exposure to tianeptine and use of a novel, extended-release, six-armed, star-shaped, drug delivery capsule. A 40-year-old male with a history of depression, anxiety, ethanol, opioid, cannabis, and tobacco use disorders presented to the emergency department (ED) from a substance abuse residential recovery treatment program after developing hypertension, tachycardia, and tremor for two day. He used an extended-release, six-armed, star-shaped, drug delivery device he purchased online, filling each arm with 15 mg of tianeptine (90 mg total). His intention was to mitigate the symptoms of kratom/opioid withdrawal through this extended-release method while simultaneously undergoing formal treatment for ethanol withdrawal. Tianeptine is an atypical tricyclic antidepressant that exerts complex mechanisms of action including serotonin (5-HT) neuromodulation as well as full µ-opioid and ∂-opioid receptor agonism. The capsule itself is made of caprolactone, which is a bioabsorbable material similar to absorbable sutures, initially developed as a long-term enteral antimalarial delivery method and is not FDA approved for human use. Over the course of the patients two day hospitalization course he developed symptoms consistent with uncomplicated ethanol withdrawal, which were treated with as-needed phenobarbital. No clinical manifestations of opioid or serotonin toxicity developed. Serial EKGs and telemetry monitoring remained unchanged. The patient was then medically cleared and discharged back to the residential recovery treatment program.