13-Year-Old Female With New Onset Multifocal Pulmonary Ground-Glass Opacities.

A 13-year-old female who recently emigrated from Honduras presented to an emergency department in Texas with a 2-month history of weight loss, fatigue, cough, and progressive shortness of breath. Her symptoms started with a nonproductive cough, and she later developed dyspnea on exertion and orthopnea. On physical examination, she was tachycardic and tachypneic. She had a thin, emaciated body habitus. She was visibly in respiratory distress with nasal flaring, tracheal tugging, and intercostal and subcostal retractions. She had diminished breath sounds at the bases and bibasilar crackles. A computed tomography scan of the chest revealed multifocal ground-glass opacities throughout all lobes of both lungs with small bilateral pleural effusions and prominent bilateral hilar lymph nodes. We will discuss the approach to the initial evaluation and subsequent diagnosis.

Clinical use and mechanisms of resistance for PARP inhibitors in homologous recombination-deficient cancers.

Cells are continuously subjected to DNA damaging agents. DNA damages are repaired by one of the many pathways guarding genomic integrity. When one or several DNA damage pathways are rendered inefficient, cells can accumulate mutations, which modify normal cellular pathways, favoring abnormal cell growth. This supports malignant transformation, which can occur when cells acquire resistance to cell cycle checkpoints, apoptosis, or growth inhibition signals. Mutations in genes involved in the repair of DNA double strand breaks (DSBs), such as BRCA1, BRCA2, or PALB2, significantly increase the risk of developing cancer of the breast, ovaries, pancreas, or prostate. Fortunately, the inability of these tumors to repair DNA breaks makes them sensitive to genotoxic chemotherapies, allowing for the development of therapies precisely tailored to individuals' genetic backgrounds. Unfortunately, as with many anti-cancer agents, drugs used to treat patients carrying a BRCA1 or BRCA2 mutation create a selective pressure, and over time tumors can become drug resistant. Here, we detail the cellular function of tumor suppressors essential in DNA damage repair pathways, present the mechanisms of action of inhibitors used to create synthetic lethality in BRCA carriers, and review the major molecular sources of drug resistance. Finally, we present examples of the many strategies being developed to circumvent drug resistance.

Disseminated Coccidioidomycosis Following Insufficient Treatment at Initial Presentation: Case Report.

A 35-year-old male presented to our university hospital with night sweats, fevers, ulcerated skin lesions to the lower mouth and posterior neck, shortness of breath, and an enlarging cervical lymph node. The patient was evaluated 2 months prior for respiratory symptoms, cervical lymphadenopathy, and skin lesions resulting in a diagnosis of primary pulmonary coccidioidomycosis and was treated with a 4-week course of fluconazole. On presentation to our hospital, initial laboratory test results revealed leukocytosis, increased liver enzymes, elevated inflammatory markers, and hypercalcemia. Computed tomography scan of the chest revealed lung nodules in a miliary pattern and prominent mediastinal lymphadenopathy. Magnetic resonance imaging revealed multiple vertebral and iliac bone lesions, as well as bilateral psoas muscle lesions. Serum ELISA (enzyme linked immunosorbent assay) detected elevated serological markers against coccidioides, and sputum culture revealed coccidioides arthroconidia, confirming the presence of an acute coccidioides infection. Biopsy of the right iliac crest and cervical lymph node revealed spherules resembling coccidioides, escalating the diagnosis to disseminated coccidioidomycosis. The patient's hospital course was complicated by septic shock, acute respiratory distress syndrome requiring several days of mechanical ventilation, and acute kidney injury. He was ultimately treated with several weeks of voriconazole and liposomal amphotericin-B. He made a full recovery and was discharged on an extended course of oral voriconazole. Our case highlights the importance of recognition and appropriate treatment duration of disseminated coccidioidomycosis at initial presentation. Failure to do so may lead to increased morbidity and mortality.