Disruption of proteome by an oncogenic fusion kinase alters metabolism in fibrolamellar hepatocellular carcinoma.

Fibrolamellar hepatocellular carcinoma (FLC) is a usually lethal primary liver cancer driven by a somatic dysregulation of protein kinase A. We show that the proteome of FLC tumors is distinct from that of adjacent nontransformed tissue. These changes can account for some of the cell biological and pathological alterations in FLC cells, including their drug sensitivity and glycolysis. Hyperammonemic encephalopathy is a recurrent problem in these patients, and established treatments based on the assumption of liver failure are unsuccessful. We show that many of the enzymes that produce ammonia are increased and those that consume ammonia are decreased. We also demonstrate that the metabolites of these enzymes change as expected. Thus, hyperammonemic encephalopathy in FLC may require alternative therapeutics.

Methodologies to unlock the molecular expression and cellular structure of ocular lens epithelial cells.

The transparent ocular lens in the anterior chamber of the eye is responsible for fine focusing of light onto the retina. The lens is entirely cellular with bulk of the tissue composed of fiber cells, and the anterior hemisphere of the lens is covered by a monolayer of epithelial cells. Lens epithelial cells are important for maintaining fiber cell homeostasis and for continual growth of the lens tissue throughout life. Cataracts, defined as any opacity in the lens, remain the leading cause of blindness in the world. Following cataract surgery, lens epithelial cells can undergo a process of epithelial-to-mesenchymal transition (EMT), leading to secondary cataracts due to posterior capsular opacification (PCO). Since the epithelial cells make up only a small fraction of the lens, specialized techniques are required to study lens epithelial cell biology and pathology. Studies using native lens epithelial cells often require pooling of samples to obtain enough cells to make sufficient samples for traditional molecular biology techniques. Here, we provide detailed protocols that enable the study of native mouse lens epithelial cells, including immunostaining of the native lens epithelium in flat mounts, extraction of RNA and proteins from pairs of lens epithelial monolayers, and isolation of lens epithelial cells for primary culture. These protocols will enable researchers to gain better insight on representative molecular expression and cellular structure of lens epithelial cells. We also provide comparative data between native, primary culture, and immortalized lens epithelial cells and discuss the advantages and disadvantages of each technique presented.

Vitamin D Toxicity Managed with Peritoneal Dialysis.

Vitamin D deficiency is a global health issue that afflicts more than one billion children and adults worldwide. Vitamin D supplementation has increased over the years, whether through medical prescriptions, over-the-counter, or online purchasing. This is driven by a more recognized association between vitamin D sufficiency status and lower risk of cancer. In addition, more recently, it is used as a potential prophylactic and treatment for COVID-19 infection. This can lead to toxicity from overingestion. While rare, it has been reported in the literature. In this case report, we present a 75-year-old man with severe hypercalcemia secondary to vitamin D toxicity managed with peritoneal dialysis. He presented with biochemical evidence of hypercalcemia, acute kidney injury, and pancreatitis. Workup for his hypercalcemia led to the diagnosis of vitamin D toxicity as shown by a level greater than 200 ng/dL (Ref: 20-50 ng/mL) was confirmed by liquid chromatography-mass spectroscopy. Cornerstone medical management of hypercalcemia was provided which included aggressive intravenous fluid hydration, intravenous diuretics, calcitonin, bisphosphonate, and corticosteroid therapy. At every interruption of therapy, calcium levels trended upward. A thorough literature review yielded the finding of a sole case report from 1966 presented at the Third International Congress of Nephrology, in which peritoneal dialysis was used in the management of vitamin D toxicity and hypercalcemia. This modality is established to cause vitamin D deficiency. In collaboration with the nephrology team, 10 sessions of peritoneal dialysis were undertaken with resolution of hypercalcemia and downtrend in 25-hydroxyvitamin D levels as measured by dilution.

Use of MASCC score in the inpatient management of febrile neutropenia: a single-center retrospective study.

PURPOSE: The Multinational Association for Supportive Care in Cancer (MASCC) score is used to risk stratify outpatients with febrile neutropenia (FN). However, it is rarely used in hospital settings. We aimed to describe management, use of MASCC score, and outcomes among hospitalized patients with FN. METHODS: We conducted a retrospective cohort study of patients with cancer and FN. We collected patient demographics, cancer characteristics, microbiological profile, MASCC score, utilization of critical care therapies, documentation of goals of care (GOC), and inpatient deaths. Outcomes associated with low- (≥ 21) versus high-risk (< 21) MASCC scores are presented as absolute differences. RESULTS: Of 193 patients, few (2%, n = 3) had MASCC scores documented, but when calculated, 52% (n = 101) had a high-risk score (< 21). GOC were discussed in 12% (n = 24) of patients. Twenty one percent (n = 40) required intermediate/ICU level of care, and 12% (n = 23) died in the hospital. Those with a low-risk score were 33% less likely to require intermediate/ICU care (95% CI 23 to 44%) and 19% less likely to die in the hospital (95% CI 10% to 27%) compared to those with high-risk score. CONCLUSIONS: MASCC score was rarely used for hospitalized patients with FN, but high-risk score was associated with worse outcomes. Education efforts to incorporate MASCC score into the workflow may help identify patients at high risk for complications and help clinicians admit these patients to a higher level of care (e.g., intermediate/ICU care) or guide them to initiate earlier GOC discussions.

Small Cell Lung Cancer with Pituitary Metastasis Presenting as Secondary Adrenal Insufficiency: A Case Report and Literature Review.

BACKGROUND Pituitary gland metastasis is rarely the initial presentation of metastatic cancer. Most cases of pituitary gland metastasis are asymptomatic with diabetes insipidus being the most common symptomatic presentation. It can rarely present with symptoms of hormone underproduction such as secondary adrenal insufficiency. Although pituitary gland metastasis is rare, it is underestimated, as it is commonly misdiagnosed with pituitary gland adenoma due to the lack of clear radiological criteria differentiating between both. CASE REPORT We present a case of a 62-year-old male who presented with weakness, blurry vision, and persistent hypoglycemia despite intravenous dextrose infusion and having discontinued taking his diabetes medications. Chest x-ray showed a left hilar mass, while computed tomography scan demonstrated a left superior hilar mass and hilar lymphadenopathy with bilateral adrenal nodules and a T6 vertebral lesion suspicious for metastasis. Further workup showed secondary adrenal insufficiency with a low adrenocorticotropic hormone (ACTH) level. Vertebral biopsy was performed and confirmed the diagnosis of small cell carcinoma of the lung. This was followed by a brain magnetic resonance imaging (MRI), which showed multiple metastatic lesions with an enhancing mass involving the right clivus, sella, and suprasellar cistern with mass effect on the optic chiasm and involvement of the cavernous sinus supporting the diagnosis of pituitary gland metastasis of small cell lung cancer. The patient received brain radiation, and repeated MRI showed regression of the previous MRI findings. CONCLUSIONS Secondary adrenal insufficiency is an unusual presentation of pituitary gland metastasis. Physicians should take into consideration both radiological findings and presentation to differentiate between pituitary gland metastasis and pituitary adenoma.