BackgroundImmune‐checkpoint inhibitors have been shown to improve survival in melanoma patients, but can also trigger immune‐related endocrinopathies, especially hypophysitis and thyroid dysfunction.MethodsTo assess the incidence and the spectrum of endocrinopathies in melanoma patients treated with immunotherapy a prospective observational study was conducted. Forty out of 339 patients, treated with immune‐checkpoint inhibitors, developed endocrinopathies. All patients had hormonal functional tests at screening (before the initiation of immunotherapy) and during follow‐up.ResultsThe total incidence of endocrinopathies was 11.8%, 13.4% due to anti‐PD1/PDL1, 5% due to anti‐CTLA4, and 18.5% due to sequential and/or combination treatment. Twenty‐one patients (6.2%) presented with isolated anterior hypophysitis, eleven (3.2%) with primary thyroid dysfunction and eight (2.4%) with both abnormalities. The most frequent anterior pituitary hormone deficiency was central adrenal insufficiency, followed by central hypothyroidism and hypogonadotrophic hypogonadism. None of the patients with corticotroph axis failure recovered during follow‐up. Endocrinopathies occurred after a median of 22 weeks (range: 4‐156) from treatment initiation. Of note, sequential and/or combination therapy with anti‐CTLA4 and anti‐PD1/anti‐PDL1 led to an almost threefold incidence of hypophysitis compared to either monotherapy. Only one of 120 patients receiving anti‐CTLA4 monotherapy developed primary hypothyroidism.ConclusionsOur cohort demonstrated an increased incidence of hypophysitis with anti‐PD1/anti‐PDL1 in contrast to the rarity of primary thyroid dysfunction with anti‐CTLA4 treatment. These results could be attributed to genetic/ethnic differences. Sequential treatment is, for the first time to our knowledge, reported to increase the risk of developing hypophysitis to a level as high as that of combination therapy.

Hypercalcemia of malignancy is the most common cause of hypercalcemia in hospitalized patients. It is associated with a poor prognosis, since it reflects an advanced cancer stage. Among all cancer in females, breast cancer is the most common malignancy, and it has the highest prevalence of hypercalcemia. Approximately 70% of patients with breast cancer have bone metastases and 10% of them will have hypercalcemia as a complication at some point in the disease. Herein, we report a 69-year-old female patient with metastatic breast cancer, who developed severe hypercalcemia in the course of her disease and was diagnosed with humoral hypercalcemia of malignancy (HHM). Intense hydration along with corticoisteroids and antiresorptive medication (calcitonin, bisphosphonates and denosumab) were administered to the patient. Despite the above treatment, serum calcium levels remain elevated and calcimimetic cinacalcet was added. Upon discontinuation of cinacalcet, calcium levels were raised and returned back to the normal levels following re-initiation of the calcimimetic. Her calcium level restored to normal, and she was discharged with the following medical treatment: denosumab monthly, and cinacalcet at a titrated dose of 90 mg per day. The patient is followed as an outpatient and 11 months later, her calcium level remained within the normal range.Learning points:Hypercalcemia of malignancy is the most common cause of hypercalcemia in hospitalized patients.Breast cancer has the highest prevalence of hypercalcemia.The cornerstone of therapy remains the intense hydration and intravenous bisphosphonates (preferably zoledronic acid).In case of persistent hypercalcemia of malignancy, the administration of calcimimetic cinacalcet could be an additional effective therapeutic option.

Detecting a fall through visual cues is emerging as a hot research agenda for improving the independence of the elderly. However, the traditional motion-based algorithms are very sensitive to noise, reducing fall detection accuracy. Another approach is to efficiently localize and then track the foreground object followed by measurements that aid the identification of a fall. However, to perform robust and stable tracking over a long time is a challenging research aspect in computer vision society. In this paper, we introduce a stable human tracker able to efficiently cope with the trade-off between model stability (accurate tracking performance) and adaptability (model evolution to visual changes). In particular, we introduce local geometrically enriched mixture models for background modelling. Then, we incorporate iterative motion information methods, constrained by shape and time properties, to estimate high confidence image regions for background model updating. This way, we are able to detect and track the foreground objects even when visual conditions are dynamically changed over time (luminosity or background/foreground changes or active cameras).

We hereby report the identification of a novel heterozygous loss-of-function mutation of the CASR gene in a Greek family from Nisyros island. Functional studies are needed to clarify the exact role of this mutation in CASR activity.