ALK-negative lung inflammatory myofibroblastic tumor in a young adult: A case report and literature review of molecular alterations

Rationale:Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal tumor that is prevalent among children and adolescents. Surgery is the most important therapeutic approach for IMT and complete resection is recommended. Although 50% of IMTs show anaplastic lymphoma kinase (ALK) rearrangements, crizotinib has proven an effective therapeutic approach. However, the genetic landscape of this tumor is still not fully understood and treatment options are limited, especially in the majority of ALK-negative tumors.Patient concerns:We describe the clinical case of a healthy 18-year-old female in whom a pulmonary nodule was incidentally detectedDiagnoses:Following a small increase in the size of the nodule, the patient underwent both ¹⁸FDG-PET/CT and ⁶⁸Ga-PET/CT, resulting in a suspicion of bronchial hamartoma.Interventions:The patient underwent surgery and a salivary gland-like lung tumor was diagnosed.Outcomes:After surgery, the patient was referred to our cancer center, where a review of the histology slides gave a final diagnosis of ALK-negative lung IMT. Given the histology, it was decided not to administer adjuvant therapy and the patient was placed in a 3-monthly follow-up program. The patient is still disease-free 2 years post-surgery.Lessons:Although there is no standard of care for the treatment of IMT, identifying genomic alterations could help to redefine the management of patients with negative-ALK disease. Our review of the literature on IMT and other kinase fusions revealed, in addition to ALK rearrangements, the potential association of ROS1, NTRK, RET, or PDGFR beta alterations with the tumor.     

Ursodeoxycholic acid in the treatment of cholestasis of pregnancy: a randomized double-blind study controlled with placebo

Backgrounds/Aims: Intense pruritus and the risk of stillbirths and premature deliveries justify the search for an effective pharmacologic treatment of intrahepatic cholestasis of pregnancy. This study was designed to test the efficacy of ursodeoxycholic acid in maternal pruritus, the biochemical abnormalities and the outcome of pregnancy, in patients with intrahepatic cholestasis of pregnancy of early onset.Methods: Pregnant patients hospitalized in a secondary case-referral center with intense pruritus and abnormal serum levels of bile salts and aminotransferases, detected before week 33 of pregnancy, were randomly assigned to receive ursodeoxycholic acid, 1 g per day orally, or an identical placebo, until delivery, in a double-blind study. A 3-week trial period was chosen to compare drug and placebo effects. The follow-up was extended for 3 months after delivery.Results: Twenty-four patients entered the trial; eight had deliveries before 2 weeks of treatment and one dropped out. The study was then completed in 15 patients: eight received ursodeoxycholic acid and seven placebo. No adverse effects were detected in the mother or in their babies. After 3 week of treatment, patients receiving ursodeoxycholic acid (mean daily) dose 16 mg/kg body weight) had a significant improvement in pruritus (p<0.02), In serum bilirubin (0.36±0.19 mg/dl (mean±SD) versus 0.95±0.48 in patients receiving placebo, p<0.01), in aspartate aminostransferase (52±42 IU/l vs 98±44, p<0.05) and in alanine aminotransferase (54±50 IU/l vs 229±154, p<0.01); serum total bile salts also tended to be lower in patients receiving ursodeoxycholic acid (26.3±33.7 μmol/l vs 55.0±44.8, p N.S.). Deliveries occurred at or near term in all mothers who received ursodeoxycholic acid (mean week of pregnancy: 38), while they occurred before week 36 of pregnancy in five patients who received placebo, including one stillbirth. All babies born alive had birth weights adequate for gestational age and they were thriving normally 3 months after delivery.Conclusions: Ursodeoxycholic acid is effective and safe in patients with intrahepatic cholestasis of pregnancy of early onset, attenuating pruritus and correcting some biochemical abnormalities in the mothers. Relevant aspects of fetal outcome were also improved in patients receiving ursodeoxycholic acid compared to placebo.     

Epidemiology and outcomes of bacterial meningitis in Mexican children: 10-year experience (1993-2003).

BACKGROUND: Acute bacterial meningitis remains an important cause of morbidity, neurologic sequelae, and mortality in children in Latin America. METHODS: We retrospectively reviewed the hospital-based medical records of children diagnosed with acute bacterial meningitis, aged 1 month to 18 years, at a large inner city referral Hospital in Mexico City, for a 10-year period (1993-2003). To characterize the epidemiology, clinical features, and outcomes of acute bacterial meningitis, we subdivided our study into two time periods: the period prior to the routine use of Haemophilus influenzae type b (Hib) vaccine (1993-1998) and the period after the vaccine became available (1999-2003). RESULTS: A total of 218 cases of acute bacterial meningitis were identified during the study period. The most frequently affected age group was that of children aged between 1 and 6 months. Hib was the most commonly isolated pathogen, found in 50% of cases. However, its incidence declined significantly after the introduction of the combined diphtheria, tetanus, pertussis, hepatitis B, and conjugated Hib (DTP-HB/Hib) pentavalent vaccine into the universal vaccination schedule for children in 1998. Streptococcus pneumoniae followed as the second most commonly isolated bacterial pathogen. Neisseria meningitidis was isolated in only a few cases, confirming the historically low incidence of this pathogen in Mexico. Identified risk factors for death were found to include the presence of septic shock and intracranial hypertension, but were not attributable to any particular bacterial pathogen. CONCLUSIONS: In our hospital, acute bacterial meningitis remains a severe disease with important sequelae and mortality. The incidence of Hib meningitis cases has declined since the introduction of the Hib vaccine. However, S. pneumoniae persists as an important cause of bacterial meningitis, highlighting the need for the implementation of vaccination policies against this pathogen.     

Molecular Epidemiology of Plasmodium falciparum Malaria Outbreak,Tumbes, Peru, 2010–2012

During 2010–2012, an outbreak of 210 cases of malaria occurred in Tumbes, in the northern coast of Peru, where no Plasmodium falciparum malaria case had been reported since 2006. To identify the source of the parasite causing this outbreak, we conducted a molecular epidemiology investigation. Microsatellite typing showed an identical genotype in all 54 available isolates. This genotype was also identical to that of parasites isolated in 2010 in the Loreto region of the Peruvian Amazon and closely related to clonet B, a parasite lineage previously reported in the Amazon during 1998–2000. These findings are consistent with travel history of index case-patients. DNA sequencing revealed mutations in the Pfdhfr, Pfdhps, Pfcrt, and Pfmdr1 loci, which are strongly associated with resistance to chloroquine and sulfadoxine/pyrimethamine, and deletion of the Pfhrp2 gene. These results highlight the need for timely molecular epidemiology investigations to trace the parasite source during malaria reintroduction events.     

Postpartum depression in Mexican women with autoimmune rheumatic diseases

Clinical Rheumatology -     

Primary aldosteronism and hypertensive disease

Recent studies in hypertensive populations that have used the serum aldosterone (SA) to plasma renin activity (PRA) ratio as a screening test have demonstrated a high prevalence of primary aldosteronism (PA). This frequency is higher than that previously described when hypokalemia was used as a screening tool. However, other factors, such as the characteristics of hypertensive disease, could also influence the prevalence of PA. We studied 609 essential hypertensive patients, classified according to the Joint National Committee VI (JNC VI), in 3 different stages depending on the severity of their hypertensive disease. We measured SA and PRA and calculated the SA-PRA ratio for all patients. An SA-PRA ratio >25 was detected in 63 of 609 patients, and the fludrocortisone test confirmed the PA diagnoses in 37 of 609 (6.1%) cases. PA prevalence according to hypertension stage was as follows: stage 1, 6 of 301 cases (1.99%); stage 2, 15 of 187 cases (8.02%); and stage 3, 16 of 121 cases (13.2%). PA patients were slightly younger than the other hypertensive patients (48.4+/-10.5 vs 53.6+/-10.2 years; P<0.05). Serum potassium levels were normal in 36 of 37 PA patients; only 1 patient had minor hypokalemia. Computed tomography scans showed bilateral adrenal enlargement in 7 and an adrenal nodule in 2 cases. In summary, we found a high frequency of PA in essential hypertensives classified in stages 2 and 3 according to the JNC VI. The low frequency of computed tomography scan abnormalities and hypokalemia suggests that the diagnosis for most PA patients corresponds to attenuated forms of the disease.