A diagnosis of late-onset Myasthenia gravis unmasked by topical antibiotics

Myasthenia Gravis (MG) is a disorder of the neuromuscular junction (NMJ) that manifests as fluctuating fatiguable weakness of the muscles. There are many factors that can exacerbate myasthenia symptoms including a variety medications and drugs, systemic illness, and pregnancy. A number of medications have been implicated in exacerbating MG symptoms, including aminoglycosides. We present a case of an elderly female with newly diagnosed MG following the use of tobramycin eye drops for 3 days. There have been limited reports in the literature of topical medications that exacerbate MG symptoms. Clinicians prescribing tobramycin eye drops (or other associated medications) should have a high index of suspicion of MG as early discontinuation and therapy will limit long-term morbidity and mortality in these patients

Acute Chest Syndrome Progressing to ARDS in a Patient of 25-Week Gestation

Acute chest syndrome is a complication of sickle cell disease and represents the highest cause of mortality in those afflicted with the disorder. Pregnancy represents an increased risk for complications of sickle cell disease in both the mother and fetus. We present a case of a 20-year-old patient with known sickle cell disease who was at 25-week gestation and developed acute chest syndrome refractory to conventional therapies and requiring emergency cesarean section. Following delivery, the patient developed acute respiratory distress syndrome (ARDS) requiring extracorporeal membrane oxygenation (ECMO). The patient and infant eventually made full recoveries. This case highlights the importance of aggressive management of ACS and careful monitoring in a pregnant patient

A woman with dyspnea and recurrent pneumothorax: when dyspnea is not asthma

Lymphangioleiomyomatosis (LAM) is a rare disease characterized by cystic lung lesions, lymphatic abnormalities, and angiomyolipomas. It can take a significant amount of time to diagnose LAM due to the vague symptoms of fatigue, progressive dyspnea, pneumothorax, and pleural effusion. We present a case of a 29-year-old woman with recurrent spontaneous pneumothorax and progressive dyspnea who was initially misdiagnosed with asthma and was later found to have LAM. As with all rare diagnoses, there needs to be a suspicion of the disease in order for a further workup to be initiated. In patients with a compatible High-resolution CT scan of the chest, a high vascular endothelial growth factor-D (VEGF-D) value is diagnostic for LAM, and no other confirmatory test is needed

A devastating cardiovascular event in an adult cystic fibrosis patient: An unforeseen outcome of increasing life expectancy

The improving life expectancy for CF is known to be one of the biggest success stories in medicine. Life expectancy has increased from 6 months during the early 20th century to 42.7 years from in 2012–2016. As the life expectancy of CF patients has increased, it is important to consider other co-morbidities that these patients may encounter, and the impact this may have on their morbidity and mortality. We present a case of a 33-year-old male admitted to the hospital for a CF exacerbation who had an acute neurological decompensation due to an infarction of his right occipital and posterior temporal lobe

Suppression of tumor cell invasiveness and in vivo tumor growth by microRNA-874 in non-small cell lung cancer

MicroRNAs are a novel family of small non-coding RNAs that regulate the expression of several genes involved in normal development as well as human disorders including cancer. Here we show that miR-874 plays a tumor suppressor role in non-small cell lung cancer (NSCLC) in vitro and in vivo. In silico target prediction analysis revealed numerous genes associated with tumor progression including MMP-2 and uPA as the putative target genes of miR-874. Our preliminary in situ hybridization experiments demonstrated the diminution of miR-874 expression in lung cancer tissues compared to their normal counter parts. Overexpression of miR-874 in CD133-positive cancer stem cell (CSC) population led to a significant loss in CSC-phenotype and enhanced sphere de-differentiation into epithelial-like cells. Restoration of miR-874 expression drastically reduced cell invading ability in comparison to mock and control-miR-treated cells by suppressing the protein levels of MMP-2 and uPA. In in vivo experiments, miR-874 treatment decreased orthotopic tumor growth in nude mice compared to mock and control-miR treatments. Further, the immunoreactivity of human anti-MMP-2 and anti-uPA was significantly reduced in tumor sections from mice that received miR-874 treatment. In conclusion, our study highlights the possible tumor suppressor role of miR-874 in NSCLC-initiating cells and suggests miR-874 as a potential target in the treatment of NSCLC

Long-term safety and efficacy of tezacaftor–ivacaftor in individuals with cystic fibrosis aged 12 years or older who are homozygous or heterozygous for Phe508del CFTR (EXTEND): an open-label extension study

Background: Tezacaftor-ivacaftor is an approved cystic fibrosis transmembrane conductance regulator (CFTR) modulator shown to be efficacious and generally safe and well tolerated over 8-24 weeks in phase 3 clinical studies in participants aged 12 years or older with cystic fibrosis homozygous for the Phe508del CFTR mutation (F/F; study 661-106 [EVOLVE]) or heterozygous for the Phe508del CFTR mutation and a residual function mutation (F/RF; study 661-108 [EXPAND]). Longer-term (>24 weeks) safety and efficacy of tezacaftor-ivacaftor has not been assessed in clinical studies. Here, we present results of study 661-110 (EXTEND), a 96-week open-label extension study that assessed long-term safety, tolerability, and efficacy of tezacaftor-ivacaftor in participants aged 12 years or older with cystic fibrosis who were homozygous or heterozygous for the Phe508del CFTR mutation. Methods: Study 661-110 was a 96-week, phase 3, multicentre, open-label study at 170 clinical research sites in Australia, Europe, Israel, and North America. Participants were aged 12 years or older, had cystic fibrosis, were homozygous or heterozygous for Phe508del CFTR, and completed one of six parent studies of tezacaftor-ivacaftor: studies 661-103, 661-106, 661-107, 661-108, 661-109, and 661-111. Participants received oral tezacaftor 100 mg once daily and oral ivacaftor 150 mg once every 12 h for up to 96 weeks. The primary endpoint was safety and 'tolerability. Secondary endpoints were changes in lung function, nutritional parameters, and respiratory symptom scores; pulmonary exacerbations; and pharmacokinetic parameters. A post-hoc analysis assessed the rate of lung function decline in F/F participants who received up to 120 weeks of tezacaftor-ivacaftor in studies 661-106 (F/F) and/or 661-110 compared with a matched cohort of CFTR modulator-untreated historical F/F controls from the Cystic Fibrosis Foundation Patient Registry. Primary safety analyses were done in all participants from all six parent studies who received at least one dose of study drug during this study. This study was registered at ClinicalTrials.gov (NCT02565914). Findings: Between Aug 31, 2015, to May 31, 2019, 1044 participants were enrolled in study 661-110 from the six parent studies of whom 1042 participants received at least one dose of study drug and were included in the safety set. 995 (95%) participants had at least one TEAE; 22 (2%) had TEAEs leading to discontinuation; and 351 (34%) had serious TEAEs. No deaths occurred during the treatment-emergent period; after the treatment-emergent period, two deaths occurred, which were both deemed unrelated to study drug. F/F (106/110; n=459) and F/RF (108/110; n=226) participants beginning tezacaftor-ivacaftor in study 661-110 had improvements in efficacy endpoints consistent with parent studies; improvements in lung function and nutritional parameters and reductions in pulmonary exacerbations observed in the tezacaftor-ivacaftor groups in the parent studies were generally maintained in study 661-110 for an additional 96 weeks. Pharmacokinetic parameters were also similar to those in the parent studies. The annualised rate of lung function decline was 61·5% (95% CI 35·8 to 86·1) lower in tezacaftor-ivacaftor-treated F/F participants versus untreated matched historical controls. Interpretation: Tezacaftor-ivacaftor was generally safe, well tolerated, and efficacious for up to 120 weeks, and the safety profile of tezacaftor-ivacaftor in study 661-110 was consistent with cystic fibrosis manifestations and with the safety profiles of the parent studies. The rate of lung function decline was significantly reduced in F/F participants, consistent with cystic fibrosis disease modification. Our results support the clinical benefit of long-term tezacaftor-ivacaftor treatment for people aged 12 years or older with cystic fibrosis with F/F or F/RF genotypes. Funding: Vertex Pharmaceuticals Incorporated