An Uncommon Presentation of Pulmonary Tularemia: A Case Report and Literature Review.

Francisella tularensis is a re-emerging organism causing more significant outbreaks of tularemia and fear of bioterrorism. It can be challenging to recognize tularemia due to its variable presentation, especially in low-incidence areas. Physicians must be mindful of this life-threatening infectious disease and consider it a differential diagnosis in patients with fever of unknown origin. We encountered a case of pulmonary tularemia with a unique presentation of severe headache and fever.

Splenic Laceration: A Rare Complication of Colonoscopy.

Splenic injury is usually seen with penetrating or blunt abdominal trauma. It is also one of the rare complications of colonoscopy. Various patient and procedural factors have been reported to increase the risk of this dreaded complication. We present a case of splenic injury after outpatient colonoscopy where intra-abdominal adhesions from previous abdominal surgeries were presumed to be the cause of splenic injury. Our patient had improved outcomes with timely diagnosis and intervention.

Hypogammaglobulinemia following COVID-19 infection in a patient on maintenance rituximab.

Hypogammaglobulinemia is a known side-effect of rituximab use. It is typically asymptomatic and transient, although certain factors, such as maintenance dosing and concomitant glucocorticoid use can lead to symptomatic or prolonged hypogammaglobulinemia. Patients with symptomatic hypogammaglobulinemia leading to recurrent infections may be treated with intravenous immunoglobulin therapy. Herein, we report a case of a 49-year-old male on maintenance rituximab without prior respiratory symptoms with new onset recurrent pneumonia after COVID-19 pneumonia and treatment with glucocorticoids.

Secondary Spontaneous Pneumothorax in a COVID-19 Recovered Patient.

Coronavirus disease 2019 (COVID-19) is an infectious disease primarily affecting the lungs with a spectrum of post-viral complications. There are well-described examples of pneumonia, empyema, pneumomediastinum, and spontaneous pneumothorax cases following COVID-19 infection within the literature. However, there is insufficient evidence implicating the cause of spontaneous pneumothorax in COVID-19 recovered patients. We present a previously infected COVID-19 patient who developed a secondary spontaneous pneumothorax two weeks after recovering. A review of the literature for similar cases was limited and therefore includes a summary of recommendations. Overall, the literature establishes that pneumothorax can occur during different phases of COVID-19 in patients without a history of pulmonary disease or barotrauma and is not necessarily associated with the severity of the viral infection. As in the case of our patient, the culmination of chronic inflammatory changes and an acute exacerbation from COVID-19 further predisposed him to a secondary spontaneous pneumothorax. In summary, all cases of recovered COVID-19 patients should maintain close follow-up with their physician and seek medical attention if acute respiratory symptoms develop.

Recurrent Lower Respiratory Tract Infections Due to Mounier-Kuhn Syndrome.

Mounier-Kuhn syndrome (MKS) is a rare disorder characterized by recurrent lower respiratory tract infections and bronchiectasis due to dilation of the trachea and bronchi. Diagnosis is made based on clinical suspicion along with radiographic evidence of tracheobronchomegaly. Mucolytic agents and chest physiotherapy have been shown to offer symptomatic improvement, and definitive surgical treatment is reserved for those with persistent symptoms. Herein, we report a case of MKS in a 72-year-old woman with bronchiectasis and recurrent multidrug-resistant lower respiratory tract infections.

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.

Multifactorial Pulmonary Hypertension in Systemic Sclerosis.

Pulmonary hypertension is a progressive disease often associated with multifactorial etiology. The impact of multiple causes contributing to rapid progression of the disease, to our knowledge has not been thoroughly reviewed in literature. The cause of pulmonary hypertension is often implied from pre-existing comorbidities. A diagnostic and management challenge exists when simultaneous presence of multiple plausible causes exist. Studies evaluating the rapid progression of symptoms in multifactorial pulmonary hypertension to this effect are lacking. We present a case of pulmonary arterial hypertension (PAH) in a patient with rapidly progressing symptoms to highlight the need for an early and thorough diagnostic workup.

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.

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.

Drug-induced dyspnea versus cystic fibrosis exacerbation: a diagnostic dilemma.

Cystic fibrosis (CF) is a disease caused by a mutation in the cystic fibrosis transmembrane conductance regulator protein in the epithelial membrane, and affects at least 30,000 people in the USA. There are between 900 and 1000 new cases diagnosed every year. Traditionally, CF has been treated symptomatically with pancreatic enzymes, bronchodilators, hypertonic saline, and pulmozyme. In July 2015, the US Food and Drug Administration approved Orkambi (lumacaftor/ivacaftor), a combination drug that works on reversing the effects of the defective cystic fibrosis transmembrane conductance regulator protein. Orkambi and mucolytics decrease the viscosity of mucous secretions, leading to an accumulation of hypoviscous fluid in the alveoli, resulting in dyspnea. This presentation can be mistaken for an infective exacerbation. We present a case in which a young female with CF recently started on Orkambi therapy presented to her primary care physician with dyspnea and increased respiratory secretions and was admitted to the hospital for 2 weeks of intravenous and inhaled antibiotic therapy for a presumed CF exacerbation. We highlight this case to bring awareness and educate patients and clinicians of the side-effect profile of Orkambi therapy with an intent to avoid unnecessary hospitalizations, inpatient antibiotics, and other costly medical services.

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.

Adenovirus-mediated small interfering RNA against matrix metalloproteinase-2 suppresses tumor growth and lung metastasis in mice.

Matrix metalloproteinases (MMP) are a group of proteinases that have normal physiologic roles degrading and remodeling the extracellular matrix. They also have multiple roles in different stages of tumor progression. Elevated levels of MMPs have been observed in many tumors; these increases have a strong association with the invasive phenotype. MMP-2 and MMP-9 are particularly involved in cancer invasion and metastasis. MMP inhibitors are currently being tested as therapeutic agents for a number of cancers in both preclinical models and in clinical trials. To date, clinical trials using this strategy have had limited efficacy. A major concern is the lack of specificity of commercially available MMP inhibitors. An adenoviral vector expressing small interfering RNA against the MMP-2 gene (Ad-MMP-2) was constructed to specifically inhibit MMP-2 expression. The effect of Ad-MMP-2 on invasion, angiogenesis, tumor growth, and metastasis of A549 lung cancer cell was evaluated. Ad-MMP-2 infection of lung cancer cells showed specific down-regulation of MMP-2 protein, activity, and transcription as determined by Western blotting, gelatin zymography, and reverse transcription-PCR. Ad-MMP-2 inhibition also mitigated lung cancer invasion and migration, and reduced tumor cell-induced angiogenesis in vitro. In an experimental metastatic lung tumor model, treatment of established tumors by Ad-MMP-2 inhibited s.c. tumor growth and formation of lung nodules in mice. Adenoviral-mediated RNA interference against MMP-2 has significant therapeutic potential for lung cancer and exerts some of this effect by inhibiting angiogenesis.

Inhibition of invasion, angiogenesis, tumor growth, and metastasis by adenovirus-mediated transfer of antisense uPAR and MMP-9 in non-small cell lung cancer cells.

Lung cancer is currently the leading cause of cancer deaths in the United States. Conventional therapeutic treatments, including surgery, chemotherapy, and radiation therapy, have achieved only limited success. The overexpression of proteases, such as urokinase-type plasminogen activator (uPA), its receptor (uPAR), and matrix metalloproteinases (MMP), is correlated with the progression of lung cancer. In the present study, we used a replication-deficient adenovirus capable of expressing antisense uPAR and antisense MMP-9 transcripts to simultaneously down-regulate uPAR and MMP-9 in H1299 cells. Ad-uPAR-MMP-9 infection of H1299 cells resulted in a dose- and time-dependent decrease of uPAR protein levels and MMP-9 activity as determined by Western blotting and gelatin zymography, respectively. Corresponding immunohistochemical analysis also showed that Ad-uPAR-MMP-9 infection inhibited uPAR and MMP-9 expression. As shown by Boyden chamber assay, Ad-uPAR-MMP-9 infection significantly decreased the invasive capacity of H1299 cells compared with mock and Ad-CMV (empty vector)-infected cells in vitro. Furthermore, Ad-uPAR-MMP-9 infection inhibited capillary-like structure formation in H1299 cells cocultured with endothelial cells in a dose-dependent manner compared with mock- and Ad-CMV-infected cells. Ad-uPAR-MMP-9 injection caused the regression of s.c. induced tumors after s.c. injection with H1299 lung cancer cells and inhibited lung metastasis in the metastatic model with A549 cells. These data suggest that Ad-uPAR-MMP-9 shows its antitumor activity against both established and early phases of lung cancer metastases by causing the destruction of the tumor vasculature. In summary, adenovirus-mediated inhibition of uPA-uPAR interaction and MMP-9 on the cell surface may be a promising anti-invasion and antimetastatic strategy for cancer gene therapy.