Neuroendocrine Carcinoma as a Cause of Humoral Hypercalcemia of Malignancy: A Case of a Patient With Elevated Parathyroid Hormone-Related Protein.

Humoral hypercalcemia of malignancy (HHM) is a paraneoplastic syndrome caused by elevations in parathyroid hormone-related protein (PTH-rP). HHM often presents in patients with squamous cell carcinomas of the lung, head, and neck, as well as breast, ovarian, renal, and bladder carcinomas. HHM associated with neuroendocrine carcinoma (NEC) is rarely observed. Here, we report a case of NEC-associated HHM refractory to standard calcium-reducing therapies but improved with the off-label addition of cinacalcet. A 31-year-old male with metastatic NEC presented to the emergency department (ED) with symptoms of nausea, emesis, constipation, and progressive weakness. He was being treated via a clinical trial at a tertiary referral center after failing standard therapies. He had recently been admitted at an outside facility for hypercalcemia, which had been managed with denosumab (120 mg subcutaneously) over the previous four weeks. He was admitted from the ED with a serum calcium of 14.6 mg/dL, potassium of 2.9 mmol/L, and phosphate of 1.2 mg/dL; ionized calcium was elevated at 8.0 mg/dL. Despite hydration and aggressive electrolyte replacement, his calcium increased to 15.5 mg/dL. Further laboratory evaluation revealed parathyroid hormone (PTH) of 6 pg/mL (10-65 pg/mL), 25-hydroxyvitamin D of 25 ng/mL (25-80 ng/mL), 1,25-dihydroxyvitamin D of 513 pg/mL (18-64 pg/mL), and PTH-rP of 25 pmol/L (<2.5 pmol/L), consistent with HHM. Calcitonin was avoided due to a prior hypersensitivity reaction. He received prednisone 10 mg daily and pamidronate 90 mg IV, and his calcium improved to 11.5 mg/dL. He was discharged and investigational therapy was resumed. This therapy failed, and he did not qualify for additional cancer therapy due to refractory hypercalcemia. He was started on cinacalcet, and his calcium decreased enough to permit further cancer treatment. He had multiple hospitalizations with fluctuating calcium levels and ultimately died several months later after sustaining a subarachnoid hemorrhage from a fall. In conclusion, we report a rare case of HHM associated with NEC. While many cases of HHM are effectively managed with hydration, calcitonin, antiresorptive therapies, and glucocorticoids, some are refractory. Our patient was refractory and differed from most patients with HHM in at least two ways. As mentioned previously, NEC causing HHM is quite uncommon (~2% of cases); it is unclear, but this malignancy might predispose to refractory hypercalcemia. Our patient's elevated vitamin D may also have made his HHM more resistant to treatment. Ultimately, while not first line, cinacalcet was an effective treatment in our patient. This provides additional evidence that cinacalcet may be considered for refractory hypercalcemia secondary to malignancy.

Near Complete Pathologic Response to PD-1 Inhibitor and Radiotherapy in a Patient with Locally Advanced Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) remains deadly despite advances in systemic therapies and surgical techniques. While there is increasing utilization of immune therapies across diverse cancer types, PDAC remains generally resistant to these treatments. We report a case of locally advanced PDAC treated with preoperative radiation and anti-PD-1 immunotherapy guided by preoperative PD-L1 tumor analysis. After 4 months of preoperative therapy, the patient was submitted to resection, demonstrating a near-complete pathologic response on final tumor analysis. We will discuss the relevant literature and current state of immunotherapeutics for PDAC.

Hemostatic characteristics of thawed, pooled cryoprecipitate stored for 35 days at refrigerated and room temperatures.

BACKGROUND: Cryoprecipitate's shelf life is limited due to concerns over decreased clotting factor activity and contamination with extended storage. Hemostatic characteristics of thawed cryoprecipitate stored up to 35 days at refrigerated and room temperatures were assessed. STUDY DESIGN AND METHODS: Pooled cryoprecipitate was thawed and aliquoted for storage at 1-6°C or 21-24°C. Samples were tested immediately after thawing and at 4 h, 24 h, 72 h, and weekly for 35 days. At each time point fibrinogen, factor VIII (FVIII), and von Willebrand factor (vWF) were assessed. Thrombin generation and rotational thromboelastometry (ROTEM) were also performed. Further, packed red cells, platelet concentrates, frozen plasma, and stored cryoprecipitate were combined (1:1:1:1) to simulate massive transfusion and analyzed by ROTEM. Day 35 samples were cultured for bacterial contamination. RESULTS: Precipitation was observed in refrigerated samples; however, these aggregates were easily resuspended upon warming in a 37°C water bath. No significant changes were observed in fibrinogen concentration or ROTEM at either temperature. FVIII and vWF declined significantly during storage. vWF, clot time, and thrombin generation were significantly better preserved with refrigeration. With simulated massive transfusion, fibrinogen function remained at or above the established range for whole blood at both storage temperatures. Bacterial contamination was not observed in cold stored or room temperature cryoprecipitate. CONCLUSION: The fibrinogen concentration and function of cryoprecipitate at extended storage durations are adequate for fibrinogen replacement in critical bleeding. These results support extension of the shelf life of cryoprecipitate when used for fibrinogen replacement.

Next-Generation Gene Sequencing Differentiates Hypoplastic Myelodysplastic Syndrome from Aplastic Anemia.

Hypoplastic Myelodysplastic Syndrome (h-MDS) comprises 15% of all MDS and has traditionally been difficult to distinguish from aplastic anemia (AA) by current testing. Accurate differentiation is important because treatment and prognosis differ. Since the publication of the 2008 World Health Organization classification of MDS, next-generation DNA sequencing has discovered novel mutations strongly associated with AA and MDS. Recent research supports the utility of identifying these mutations in the diagnosis and management of MDS; however, use of next-generation sequencing is not yet recommended in guidelines and the study is not routinely performed. We present a case where next-generation sequencing performed on a peripheral blood specimen aided the diagnosis and management of a 74-year-old man with h-MDS. This case adds to the growing body of evidence supporting the utility of next-generation DNA sequencing in the evaluation of MDS and h-MDS, particularly when diagnosis remains unclear after standard testing.

Centipede envenomation: bringing the pain to Hawai'i and Pacific Islands.

Scolopendra subspinipes is the only clinically significant centipede found in Hawai'i. Envenomation typically leads to extreme localized pain, erythema, induration, and tissue necrosis and possible lymphedema or lymphangitis. Mortality is uncommon and results from secondary infection or anaphylaxis. Management is supportive and includes wound care, pain control, and treatment with topical or oral antihistamines and anti-inflammatory medications.

Amphetamine positive urine toxicology screen secondary to atomoxetine.

The aim of this paper is to report the first case of atomoxetine leading to false-positive urine drug screen. An otherwise healthy 27-year-old female with a history of attention deficit hyperactivity disorder (ADHD) treated with atomoxetine had an acute onset tonic-clonic seizure. On arrival to the hospital, a urine toxicological drug screen with immunochemical cloned enzyme donor immunoassay (CEDIA) was performed. Results were positive for amphetamines; however, the presence of these substances could not be confirmed with urine gas chromatography-mass spectrometry (GC-MS). She denied any illicit drug use, herbal medications, or supplements, and her other prescription medications have not been previously known to cause a false-positive result for amphetamines. While stimulant treatments for ADHD could certainly result in a positive result on urine screen for amphetamines, there have been no reports of false-positive results for amphetamines secondary to patients using atomoxetine. We implicate atomoxetine, and/or its metabolites, as a compound or compounds which may interfere with urine drug immunoassays leading to false-positive results for amphetamines CEDIA assays.