Hypoxemic Respiratory Failure and Coccidioidomycosis-Associated Acute Respiratory Distress Syndrome.

Background: Severe coccidioidomycosis presenting with respiratory failure is an uncommon manifestation of disease. Current knowledge of this condition is limited to case reports and small case series. Methods: A retrospective multicenter review of patients with coccidioidomycosis-associated acute respiratory distress syndrome (CA-ARDS) was conducted. It assessed clinical and laboratory variables at the time of presentation, reviewed the treatment course, and compared this cohort with a national database of patients with noncoccidioidomycosis ARDS. Survivors and nonsurvivors of coccidioidomycosis were also compared to determine prognostic factors. Results: In this study, CA-ARDS (n = 54) was most common in males, those of Hispanic ethnicity, and those with concurrent diabetes mellitus. As compared with the PETAL network database (Prevention and Early Treatment of Acute Lung Injury; n = 1006), patients with coccidioidomycosis were younger, had fewer comorbid conditions, and were less acidemic. The 90-day mortality was 15.4% for patients with coccidioidomycosis, as opposed to 42.6% (P < .0001) for patients with noncoccidioidomycosis ARDS. Patients with coccidioidomycosis who died, as compared with those who survived, were older, had higher APACHE II scores (Acute Physiology and Chronic Health Evaluation), and did not receive corticosteroid therapy. Conclusions: CA-ARDS is an uncommon but morbid manifestation of infection. When compared with a national database, the overall mortality appears favorable vs other causes of ARDS. Patients with CA-ARDS had a low overall mortality but required prolonged antifungal therapy. The utility of corticosteroids in this condition remains unconfirmed.

An innovative intervention for the prevention of vaso-occlusive episodes in sickle cell disease.

OBJECTIVES: Sickle cell disease (SCD) is characterized by a mutation in the beta-globin gene resulting in abnormal hemoglobin S (HgbS). The significant sequela of SCD include anemia and recurrent vaso-occlusive episodes (VOEs) which may effectuate patients to receive chronic blood transfusions. Current pharmacotherapy options for SCD include hydroxyurea, voxelotor, Lglutamine, and crizanlizumab. Simple and exchange transfusions are often utilized as prophylaxis to prevent emergency department (ED)/urgent care (UC) visits or hospitalizations from VOEs by reducing the level of sickled red blood cells (RBCs). In addition, the treatment of VOEs involves intravenous (IV) hydration and pain management. Studies have demonstrated that sickle cell infusion centers (SCIC) decrease hospital admissions for VOEs, and IV hydration and pain medications are the key components of management employed. Thus, we hypothesized that implementing a structured infusion protocol in the outpatient setting would reduce the incidence of VOEs. METHODS: Here, we discuss two patients with SCD who were trialed on scheduled outpatient IV hydration and opioids with the goal of decreasing the frequency of VOEs in the setting of the current blood product shortage and the patients' refusal to receive exchange transfusions. RESULTS: Overall, the two patients had opposing outcomes- one demonstrated reduced frequency of VOEs, whereas the other had mixed results due to noncompliance to scheduled outpatient sessions. DISCUSSION/CONCLUSION: The use of outpatient SCICs may be an effective intervention for prevention of VOEs in patients with SCD, and further patient-centered research and quality improvement initiatives are needed to further quantify and understand the factors contributing to their efficacy.

Medullary carcinoma of the duodenum treated with pembrolizumab: a case report.

Background: Medullary carcinoma (MC) is a recognized histologic subtype of colorectal cancer characterized by poor glandular differentiation and intraepithelial lymphocytic infiltrate. However, MC originating from the small intestine is exceedingly rare, with only nine cases described in the literature. Based on previous cases, surgical resection is currently the mainstay of treatment for those with localized disease. We report the first case of a patient who presented with unresectable microsatellite instability-high (MSI-H) MC of the duodenum and was instead treated with pembrolizumab. Case Description: A 50-year-old man with history of adenocarcinoma of the proximal descending colon status post hemicolectomy and adjuvant treatment with chemotherapy and family history of Lynch syndrome presented with abdominal pain for two weeks. Computed tomography (CT) abdomen/pelvis revealed a 10.7 cm by 4.3 cm mass in the mid-portion of the duodenum abutting against the pancreatic head. Esophagogastroduodenoscopy (EGD) demonstrated circumferential, partially obstructing, intrinsic stenosis of the duodenum with ampullary involvement and likely invasion into the pancreatic head and common bile duct. Endoscopic biopsy of the primary tumor revealed poorly differentiated MC. Immunohistochemical staining showed loss of MLH1 and PMS2 expression. Staging with CT chest showed no evidence of disease. Positron emission tomography (PET) scan redemonstrated circumferential duodenal wall thickening and hypermetabolic activity with standardized uptake value (SUV) max of 26.4, as well as PET-avid epigastric, retroperitoneal, and periaortic lymphadenopathy suggestive of metastasis. He was started on pembrolizumab and found to have stable disease on repeat imaging along with significant improvement in symptoms and performance status. Conclusions: Due to the rarity of the tumor, there is no standardized approach to treatment. All patients in previously published cases underwent surgical resection. However, our patient was deemed a poor surgical candidate. Given his previous history of colon cancer and treatment with platinum-based therapy, he qualified for pembrolizumab as first line therapy for his MSI-H tumor. To our knowledge, this is the first report of MC of the duodenum as well as the first MC to be treated with pembrolizumab in the first line setting. In order to corroborate the use of immune checkpoint inhibitors as a treatment option for MC of the colon or small intestine, the aggregation of existing and future case data in this unique patient group is certainly warranted.

Targeting the Tumor Microenvironment in Acute Myeloid Leukemia: The Future of Immunotherapy and Natural Products.

The tumor microenvironment (TME) plays an essential role in the development, proliferation, and survival of leukemic blasts in acute myeloid leukemia (AML). Within the bone marrow and peripheral blood, various phenotypically and functionally altered cells in the TME provide critical signals to suppress the anti-tumor immune response, allowing tumor cells to evade elimination. Thus, unraveling the complex interplay between AML and its microenvironment may have important clinical implications and are essential to directing the development of novel targeted therapies. This review summarizes recent advancements in our understanding of the AML TME and its ramifications on current immunotherapeutic strategies. We further review the role of natural products in modulating the TME to enhance response to immunotherapy.

Outcomes of the Pregnancies with Chronic Myeloid Leukemia in the Tyrosine Kinase Inhibitor Era and Literature Review.

Chronic myeloid leukemia (CML) is a clonal myeloproliferative neoplasm (MPN) that accounts for 10% of pregnancy-associated leukemias. The Philadelphia chromosome balanced translocation, t (9:22) (q34; q11.2), is the classic mutation seen in CML. The BCR-ABL oncoprotein encoded by this mutation is a constitutively active tyrosine kinase. Tyrosine kinase inhibitor (TKI) therapy is considered a first-line treatment for CML. However, the literature has revealed risks of teratogenicity with TKI therapy during pregnancy. Understanding the risks and benefits of TKI therapy and alternative therapies such as interferon-alpha (IFN-α) will help clinicians and pregnant patients develop a personalized CML treatment plan. This manuscript presents a case series detailing the management of five pregnancies in two pregnant patients with CML and a literature review of CML management in pregnancy.

Disseminated Coccidioidomycosis Presenting as Polyarticular Septic Arthritis: A Case Report.

Coccidioidomycosis a fungal infection endemic to southwestern United States. It is caused by inhalation of spores of Coccidioides immitis. Sixty percent of infections are asymptomatic; the remaining 40% are primarily pulmonary disease. In <1% of infections, dissemination can occur. Dissemination usually affects those with impaired cellular immunity and pregnant women, and can involve bones, joints, meninges, and skin. We present the case of a 29-year-old Hispanic male who presented to the emergency department (ED) complaining of pain and swelling of right wrist and ankle as well as left knee for 2 months. He was referred to rheumatology clinic but returned to the ED as he developed spontaneous purulent drainage from his wrist. In the ED, an arthrocentesis of 2 of the joints showed total nucleated cells of 520 000/cm2 and 90 000/cm2 with 61% and 93% neutrophils, respectively. Fungal culture eventually grew Coccidioides immitis from his wrist and knee. Coccidioidomycosis complement fixation titer came back >1:512. Bone scan showed uptake of adjacent bones in the affected joints. Superimposed bacterial infection of the wrist complicated the treatment course and delayed the start of liposomal amphotericin B. Eventually patient received 12 weeks of intravenous liposomal amphotericin-B with slow clinical improvement and then switched to oral isavuconazonium for maintenance therapy. This case shows that although disseminated polyarthritis coccidioidomycosis is very rare, clinicians should keep the diagnosis of disseminated synovial coccidioidomycosis in mind in patients with risk factors.