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A 38-year-old nulliparous woman with severe obesity (BMI 66) and hypertension presented with constipation, fatigue, weakness, and poor appetite that had progressively worsened over the prior two to three weeks. Upon admission, the patient was found to have significant hypercalcemia, leukocytosis, and lactic acidosis. Computed tomography (CT) scan of the chest, abdomen, and pelvis revealed an adnexal mass with extensive lesions throughout her pelvis, abdomen, and chest. An ultrasound-guided omental core biopsy was performed, which was confirmatory for metastatic ovarian small cell carcinoma. Given her poor prognosis and clinical status, chemotherapy was likely to provide minimal benefit and ultimately the patient decided to pursue a comfort-oriented plan of care and passed away on day 9 of admission.
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Neuroendocrine tumors (NETs) are a rare subset of malignancies in the biliary tract that may have an aggressive and initially asymptomatic course. A 93-year-old female presented with four days of abdominal pain with associated nausea, jaundice, and brown-colored urine. A CT scan revealed a soft-tissue lesion measuring 1.9 x 1.5 x 1.9 cm within the distal-most aspect of the common bile duct and papilla with marked bile duct dilatation, pancreatic duct dilatation, and multiple hepatic lesions of varying sizes. The biliary stricture was palliated with a stent via endoscopic retrograde cholangiopancreatography. Biopsies taken from the biliary mass were consistent with a well-differentiated NET: World Health Organization, Grade 3. The patient was minimally symptomatic after stenting and was discharged home. She ultimately decided not to pursue further treatment and passed away two months after the initial presentation. Currently, surgical excision is considered the main and only curative treatment for localized NETs, although chemotherapy and radiation therapy may be suitable. Early detection and treatment of these rare NETs in the biliary tree can potentially result in curative treatment.
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BACKGROUND: Amitriptyline (AT) is recommended as first-line prophylactic therapy in patients with cyclic vomiting syndrome (CVS). However, significant side effects limit its use and dosing is based on trial and error. Though the Clinical Pharmacogenetic Implementation Consortium (CPIC) Guidelines recommend dosing for AT based on CY2D6 and CYP2C19 genotype profile, this is not followed in clinical practice. METHODS: This pilot study determined CYP2C19 and CYP2D6 genotypes and ascertained its association with adverse drug reactions (ADRs), clinical response, and serum concentration of AT and nortriptyline in a well-characterized cohort of adults with CVS. KEY RESULTS: Of 46 subjects with CVS, age 33 ± 12 years, 61% female, 85% Caucasian, a third (33%) had normal CYP2C19 metabolizer status, while 4% were poor, and 43% were ultrarapid metabolizers. Most (61%) had normal CYP2D6 genotype while 9% were poor and 2% were ultra-rapid metabolizers. There was no statistically significant association between genotype and ADRs, clinical response or serum drug concentration. There was a trend towards significance between genotype and clinical response, with 64% of responders having normal CYP2D6 metabolism versus 36% of nonresponders (p = 0.06). ADRs were encountered in 46% of patients with 28% discontinuing the medication as a result. CONCLUSIONS AND INFERENCES: A subset of patients with CVS have dysfunctional alleles of CYP2C19 and CYP2D6. Larger prospective studies to evaluate the clinical impact of pharmacogenomic testing in CVS are needed. This has the potential to optimize clinical management, predict ADRs and allow for personalized therapy.
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Citocromo P-450 CYP2D6 , Testes Farmacogenômicos , Adulto , Humanos , Feminino , Adulto Jovem , Pessoa de Meia-Idade , Masculino , Citocromo P-450 CYP2D6/genética , Citocromo P-450 CYP2D6/metabolismo , Estudos Prospectivos , Citocromo P-450 CYP2C19/genética , Projetos Piloto , Amitriptilina , GenótipoRESUMO
BACKGROUND: Cyclic vomiting syndrome (CVS) is a disorder of gut-brain interaction (DGBI) characterized by recurrent episodes of nausea and vomiting. Most children outgrow their CVS symptoms and develop migraine headaches, but there are limited data in adults. We thus sought to determine the natural history of CVS in adults. METHODS: We conducted a retrospective analysis of patients at a specialized tertiary care clinic. Frequency of CVS episodes, emergency department (ED) visits, and hospitalizations were recorded at the index visit and at follow-up. KEY RESULTS: Of 455 CVS patients with complete data, mean age was 33 ± 13 years, 294 (65%) were female, and 392 (86%) were Caucasian. Mean duration of follow-up was 47.4 ± 37.2 months. There was a significant reduction in frequency of CVS episodes/year (18 to 6.8), ED visits (6.1 to 2), and hospitalizations (2.3 to 0.7) (all p-values < 0.001) but only 88 (19%) of patients had complete resolution of episodes at follow-up. On multivariable regression analysis, non-white race [0.33 (0.11-0.98) p = 0.01], comorbidity count [0.77 (0.62-0.95) p = 0.01], cannabis use [0.36 (0.2-0.65) p = 0.0007], and aprepitant use [0.2 (0.08-0.005) p < 0.001] were associated with a reduced odds of complete resolution of CVS episodes. Of note, 19 patients (4%) died. CONCLUSIONS AND INFERENCES: While most adults with CVS improved with specialized care, in contrast to children, only a small subset (~1 in 5) had complete resolution of symptoms. Reasons for the effects of race, cannabis use, and comorbidity burden on outcomes in CVS are unclear and warrant further investigation.
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Cannabis , Transtornos de Enxaqueca , Adulto , Criança , Humanos , Feminino , Adulto Jovem , Pessoa de Meia-Idade , Masculino , Estudos Retrospectivos , Centros de Atenção Terciária , Vômito/diagnósticoRESUMO
BACKGROUND: Aprepitant is a neurokinin-1 receptor antagonist, and recent guidelines by the American Neurogastoenterology and Motility Society recommend its use as prophylaxis in moderate-to severe cyclic vomiting syndrome (CVS). Data are limited to small studies in children. We aimed to determine its efficacy in adults with CVS. METHODS: A retrospective review of CVS patients diagnosed using Rome criteria at a tertiary referral center was conducted. Drug response was defined as >50% reduction in symptoms and/or healthcare utilization. An intent-to-treat (ITT) analysis was conducted. KEY RESULTS: Of 96 patients prescribed aprepitant, 26 (27%) were unable to start due to cost/lack of insurance coverage. Of 70 receiving therapy, mean age was 33 ± 11 years; 51 (73%) were female and 56 (80%) Caucasian. The majority (93%) were refractory to other prophylactic medications. Aprepitant was taken thrice weekly in 51 (73%), daily in 16 (23%) and a few times a month in 3 (4%) due to cost. Fifty (71.4%) had a global symptom response to aprepitant. There was significant reduction in the number of CVS episodes (14.5 ± 11.7 to 6.2 ± 8.0, p < 0.0001), emergency department visits (4.2 ± 7.7 to 1.8 ± 3.4, p = 0.006), and hospital admissions (1.6 ± 3.9 to 0.8 ± 2.1, p = 0.02) in patients treated with aprepitant. Seven (10%) discontinued the drug due to minor side effects. CONCLUSIONS AND INFERENCES: Aprepitant is a safe and effective prophylactic medication in adults with refractory CVS. Adequate insurance coverage is a major barrier preventing its use.
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Antieméticos , Criança , Humanos , Adulto , Feminino , Adulto Jovem , Masculino , Aprepitanto/uso terapêutico , Antieméticos/uso terapêutico , Morfolinas/uso terapêutico , Vômito/tratamento farmacológico , Vômito/prevenção & controleRESUMO
Objectives: To report two different presentations of migraine with the olfactory hallucinations. A case with the typical hallucinatory olfactory symptoms preceding migraine headaches and another case with longstanding olfactory hallucinations. Background: Migraine prevails in about 12% of the general population, with the migraine aura accountable for at least one-third of these cases. The most common aura is the visual aura, followed by the sensory aura, speech, and motor auras. Olfactory hallucinations preceding the headache phase of migraine are rare. To date, the International Classification of Headache Disorders (ICHD) has not recognized them as a subset of migraine aura. Results: This report presents a patient with a typical Phantosmia (PO) aura before her migraine headache and a patient who experiences a longstanding PO aura. Conclusion: The olfactory hallucination may present differently in patients with migraine disease. Based on the clinical significance of migraine with olfactory hallucinations, we propose that the ICHD classify this phenomenon as a subtype of aura in the future. However, larger studies are still required to better assess the pathophysiology of this phenomenon.