A 21-year-old man with a history of glucose-6-phosphate dehydrogenase deficiency experienced an acute onset of atraumatic left upper abdominal and flank pain. An initial contrast-enhanced CT scan of the chest, abdomen, and pelvis revealed a consolidation in the left lower lobe, a small pleural effusion, and enlarged mesenteric lymph nodes. The patient was prescribed nonsteroidal antiinflammatory drugs for a presumed viral syndrome and was discharged. He returned the next day with increased pain, new onset of shortness of breath, and a fever of 38.6 °C. A diagnosis of community-acquired pneumonia was made, and doxycycline was prescribed. Twenty-four hours later, he presented again with severe pain, worsening dyspnea, and hypoxemia. A CT angiogram of the chest showed persistent consolidation in the left lower lobe and a now large left pleural effusion. He was admitted to the internal medicine service for the management of pneumonia and presumed para-pneumonic effusion.

A 40-year-old man with chronic myeloid leukemia presented to the hospital with recurrent dyspnea and hypoxemic respiratory failure. He presented from his outpatient transplant infectious diseases appointment with dyspnea, cough, worsening hypoxemia, acute kidney injury, and somnolence after discharge from the hospital 2 weeks prior with a similar presentation. During the previous hospital stay, he underwent bronchoscopy and alveolar lavage with negative infectious workup. He was prescribed caspofungin, amphotericin, and continued posaconazole for prior probable invasive fungal infection (elevated blood BD-glucan and pulmonary nodules). Antibiotics included previous meropenem for esophageal nocardiosis, cefepime and azithromycin during admission, and now ceftriaxone for nocardiosis in the outpatient setting for convenience of home infusion. He was prescribed diuretics for presumed volume overload. Despite home diuretics, antimicrobials, and supplemental oxygen, he re-presented with worsening symptoms.

A 56-year-old woman was admitted to our hospital, presenting with a history of recurrent fevers persisting for over 2 months. The febrile episode was self-limiting, accompanied by cough without significant expectoration, with the fever predominantly manifesting during the afternoon and evening hours. Furthermore, there were no concurrent symptoms indicative of chest tightness, wheezing, dyspnea, or hemoptysis. A CT scan in a local hospital demonstrated multifocal lymphadenopathy in the mediastinum and bilateral supraclavicular regions. The patient had neither a history of tobacco usage nor of alcohol consumption. Furthermore, there was no familial history of oncologic conditions. The patient's medical records revealed no evidence of hypertension, diabetes mellitus, coronary artery disease, infectious diseases, or immunologic disorders.

Pulmonary arterial hypertension (PAH) frequently is associated with an imbalance in antiproliferative bone morphogenic protein-2 receptor signaling and proproliferative type-II activin receptor signaling, favoring the latter. Sotatercept is an activin ligand trap that reduces the dominant detrimental activin signaling and provides clinical benefit. We report a patient with heritable PAH in whom sotatercept had neither positive nor negative effects; we relate that fact to his PAH being caused by a previously unreported variant of unknown significance (c.1276T>C, p.[Cys426Arg]) in the GDF2 gene. GDF2 encodes bone morphogenic protein type-9, the presence of which is required for proper functioning of the pulmonary microvasculature. Low levels of functionally active bone morphogenic protein type-9 contribute to PAH. As we enter an era of precision medicine for patients with PAH with increasingly costly therapies, genetic screening may direct appropriate therapy and limit the use of expensive but likely ineffective therapies.