OBJECTIVE: This study aimed to comprehensively analyze the clinical characteristics and treatment status of Chinese small cell carcinoma of the ovary hypercalcemic type (SCCOHT) patients, providing insights into this unique population and comparing findings with international literature.
METHODS: Through a meta-analysis, we collected data from published case reports and records from the Obstetrics & Gynecology Hospital of Fudan University. Demographic information, clinical presentations, tumor attributes, treatment modalities, and survival outcomes were extracted and examined alongside relevant global studies.
RESULTS: The analysis encompassed 80 Chinese SCCOHT patients, of which 62 from 33 previously reported literatures, and the other 18 were from Obstetrics & Gynecology Hospital of Fudan University. In 62 cases with stage information, A total of 25 tumors were International Federation of Gynecology and Obstetrics stage I, 3 were stage II, 19 were stage III, and 15 were stage IV. Most patients received surgery and chemotherapy, but regimens were varied. Median follow-up was 10 months (range=4-120). Elevated carbohydrate antigen 125 and serum calcium levels were consistent findings. Recurrence rates were notable, especially among stage I patients. Platinum-based chemotherapy, paclitaxel and carboplatin (n=11, 13.4%), constituted common treatment regimens.
CONCLUSIONS: This study observed demographic and clinical similarities with international datasets. And the findings emphasize the urgency for innovative therapeutic approaches to improve outcomes in SCCOHT patients. Continued research efforts are essential to enhance the knowledge surrounding this rare malignancy and to optimize its clinical management.

Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare but highly aggressive ovarian malignant neoplasm lacking a unified clinical management process. Most patients are diagnosed at an advanced stage and have an extremely poor prognosis with an overall probability of survival less than 10 %. Here, we describe the case of a patient with advanced SCCOHT achieved a survival of over 5 years after receiving multiple cycles of immunotherapy combined with anti-angiogenic therapy or CDK4/6 inhibitors. At the same time, we also summarized the case reports and clinical trials of immunotherapy in SCCOHT.

BACKGROUND: Parathyroid carcinoma (PC) is a rare endocrine malignancy causing pathological changes such as abnormal bone metabolism, elevated serum calcium, and impaired renal function, and uncontrollable hypercalcemia is the main cause of death in PC patients. The diagnosis of PC is challenging and relying on postoperative histopathology. Radical surgery at the first time is the only effective therapy to cure PC. Hungry bone syndrome (HBS) is a relatively uncommon complication of parathyroidectomy characterized by profound and prolonged hypocalcemia, timely electrolyte monitoring and alternative interventional protocols can prevent symptomatic hypocalcemia.
METHODS: A 57-year-old man presented with multiple pathological fractures and muscle atrophy as the main symptoms accompanied by bone pain, hypercalcemia, elevated parathyroid hormone (PTH), and an enlarged left-sided neck mass. After consultation of multidisciplinary team, he was treated conservatively with plaster bandage fixation and infusion of intravenous zoledronic acid; and then complete resection of parathyroid mass + removal of involved tissue structures + left thyroid and isthmus lobectomy + lymph node dissection in the VI region in left neck were performed. The postoperative histopathology suggested a diagnosis of parathyroid carcinoma. Calcium and fluid supplementation and oral levothyroxine tablets were given postoperatively. Unexpectedly, the patient\'s PTH level decreased rapidly at 24 h postoperative, and serum calcium and phosphorus decreased continuously, and he felt numb around perioral sites and fingertips, which considered to be postoperative HBS complicated by parathyroidectomy. Then, a large amount of calcium supplementation and vitamin D were given timely and the patient got better at 1 month postoperatively. At 9-month postoperative, his bone pain and fatigue were significantly relieved compared with before with calcium, phosphorus, and PTH levels at normal range.
CONCLUSIONS: The possibility of parathyroid disease, particularly PC, should be considered in the presence of multiple pathological fractures, muscle atrophy, generalized bone pain, hypercalcemia, and clear neck mass. Radical resection of the tumor lesions at the first surgery is a key element affecting the prognosis of PC, and the effective management of preoperative hypercalcemia and postoperative HBS is also of great significance for improving prognosis.

OBJECTIVE: Idiopathic infantile hypercalcemia (IIH) is a rare disorder of PTH-independent hypercalcemia. CYP24A1 and SLC34A1 gene mutations cause two forms of hereditary IIH. In this study, the clinical manifestations and molecular aspects of six new Chinese patients were investigated.
METHODS: The clinical manifestations and laboratory study of six patients with idiopathic infantile hypercalcemia were analyzed retrospectively.
RESULTS: Five of the patients were diagnosed with hypercalcemia, hypercalciuria, and bilateral medullary nephrocalcinosis. Their clinical symptoms and biochemical abnormalities improved after treatment. One patient presented at age 11 years old with arterial hypertension, hypercalciuria and nephrocalcinosis, but normal serum calcium. Gene analysis showed that two patients had compound heterozygous mutations of CYP24A1, one patient had a monoallelic CYP24A1 variant, and three patients had a monoallelic SLC34A1 variant. Four novel CYP24A1 variants (c.116G > C, c.287T > A, c.476G > A and c.1349T > C) and three novel SLC34A1 variants (c.1322 A > G, c.1697_1698insT and c.1726T > C) were found in these patients.
CONCLUSIONS: A monoallelic variant of CYP24A1 or SLC34A1 gene contributes to symptomatic hypercalcemia, hypercalciuria and nephrocalcinosis. Manifestations of IIH vary with onset age. Hypercalcemia may not necessarily present after infancy and IIH should be considered in patients with nephrolithiasis either in older children or adults.

Although bone destruction and hypercalcemia without acute peripheral blast BCR-ABL-positive acute lymphoblastic leukemia (ALL) have been reported in children, they are rare in adults. Herein, we describe a case of BCR-ABL positive ALL with a triploid karyotype, WT1, and CDKN2A mutations with hypercalcemia and bone destruction as the first manifestations. Complete remission (CR) was achieved by induction chemotherapy. BCR-ABL turned negative after treatment with dasatinib. However, computed tomography and whole-body bone scan showed extensive bone destruction. Additionally, bone biopsy showed leukemic infiltration. After treatment with dasatinib and VMCP, leukemia recurred with positive BCR-ABL. The T315I mutation occurred. The patient was surgically diagnosed with calculous cholecystitis and achieved CR2 by postoperative orebatinib and VP regimens. Later, the patient died due to a severe pulmonary infection. BCR-ABL-positive ALL with bone destruction is rare and difficult to control using tyrosine kinase inhibitor chemotherapy alone. Therefore, further exploration of more effective treatments is needed.

Primary hyperparathyroidism (PHPT) is a rare disease in pregnancy and endangers the health of both pregnant women and fetuses. However, the treatments are very limited for PHPT and most of them are unsatisfactory because of the peculiar state in pregnancy. The only curable method is parathyroidectomy which can be safely performed in the second trimester of pregnancy. In this case, we reported a pregnant woman with primary parathyroid adenoma presenting hypercalcemia and severe vomit at the end of first trimester. Finally, she got cured by microwave ablation at the end of first trimester and gave birth to a healthy baby boy.

Chronic kidney disease (CKD) often culminates in hypercalcemia, instigating severe neurological injuries that are not yet fully understood. This study unveils a mechanism, where GSK343 ameliorates CKD-induced neural damage in mice by modulating macrophage polarization through the EZH2/MST1/YAP1 signaling axis. Specifically, GSK343 downregulated the expression of histone methyltransferase EZH2 and upregulated MST1, which suppressed YAP1, promoting M2 macrophage polarization and thereby, alleviating neural injury in hypercalcemia arising from renal failure. This molecular pathway introduced herein not only sheds light on the cellular machinations behind CKD-induced neurological harm but also paves the way for potential therapeutic interventions targeting the identified axis, especially considering the M2 macrophage polarization as a potential strategy to mitigate hypercalcemia-induced neural injuries.

Human calcium sensing receptor (CaSR) senses calcium ion concentrations in vivo and is an important class of drug targets. Mutations in the receptor can lead to disorders of calcium homeostasis, including hypercalcemia and hypocalcemia. Here, 127 CaSR-targeted nanobodies were generated from camels, and four nanobodies with inhibitory function were further identified. Among these nanobodies, NB32 can effectively inhibit the mobilization of intracellular calcium ions (Ca2+i) and suppress the G12/13 and ERK1/2 signaling pathways downstream of CaSR. Moreover, it enhanced the inhibitory effect of the calcilytics as a negative allosteric modulator (NAM). We determined the structure of complex and found NB32 bound to LB2 (Ligand-binding 2) domain of CaSR to prevent the interaction of LB2 domains of two protomers to stabilize the inactive state of CaSR.

Parathyroidectomy (PTX) is an effective treatment for primary hyperparathyroidism (PHPT) patients. Postoperative hypocalcemia is a common complication after PTX. This study aimed to analyze the factors influencing serum calcium levels and the incidence of hypocalcemia after parathyroidectomy in primary hyperparathyroidism patients.
The retrospective study included 270 PHPT patients treated with PTX and collected their demographic and clinical information and their laboratory indices. Factors influencing serum calcium levels and hypocalcemia after PTX in PHPT patients were analyzed using univariate and multifactorial analyses.
First, in patients with normal preoperative serum calcium levels (2.20-2.74 mmol/L), the higher the preoperative alkaline phosphatase and serum phosphorus levels, the lower the postoperative serum calcium levels. Furthermore, the higher the preoperative serum calcium levels and the accompanying clinical symptoms, the higher the postoperative serum calcium levels. Low preoperative serum calcium levels were shown to be a risk factor for postoperative hypocalcemia (OR=0.022), and the optimal preoperative serum calcium threshold was 2.625 mmol/L (sensitivity and specificity were 0.587 and 0.712, respectively). Second, in the mild preoperative hypercalcemia group (2.75-3.00 mmol/L), the older the patient, the higher the preoperative and postoperative serum calcium levels, the higher the postoperative serum calcium; the lower the alkaline phosphatase and calcitonin levels, the higher the postoperative serum calcium levels. On the other hand, the younger the patient was, the more likely hypocalcemia blood was (OR=0.947), with an optimal age threshold of 47.5 years (sensitivity and specificity were 0.543 and 0.754, respectively). Third, in the preoperative moderate to severe hypercalcemia group (>3.0mmol/L), patients undergoing a combined contralateral thyroidectomy and a total thyroidectomy had low postoperative serum calcium levels.
Patients with different preoperative serum calcium levels had various factors influencing their postoperative serum calcium levels and postoperative hypocalcemia, which facilitated the assessment of their prognosis.

OBJECTIVE: The main purpose of this study was to explore the diagnostic performance of the Ca∗Cl/P ratio for primary hyperparathyroidism (PHPT), especially normocalcaemic PHPT (NPHPT), to assist health care providers in making reliable and rapid clinical identifications.
METHODS: From January 1, 2013, to March 31, 2023, 230 PHPT patients, including 65 with NPHPT and 230 sex- and age-matched controls, were enrolled in this retrospective study. Differences between hypercalcaemic PHPT (HPHPT) and NPHPT and between them and their respective controls were analyzed. The diagnostic accuracy of the Ca∗Cl/P ratio, Ca/P ratio, Cl/P ratio and albumin-corrected calcium was assessed by the area under the receiver operating characteristic curve.
RESULTS: Compared with corresponding controls, NPHPT and HPHPT patients both had significantly higher Ca ∗ Cl/P ratios (271.64 ± 51.74 vs 192.71 ± 26; 419.91 ± 139.11 vs 199.14 ± 36.75, P < .001). In the overall cohort, the ROC-AUC of the Ca∗Cl/P ratio (0.964, 95% CI = 0.943-0.979) for diagnosis of PHPT patients was superior to albumin-corrected calcium (0.959, 95% CI = 0.934-0.973), the Ca/P ratio (0.956, 95% CI = 0.934-0.973), and the Cl/P ratio (0.923, 95% CI = 0.895-0.946). A Ca ∗ Cl/P ratio above 239.17 mmol/L, with sensitivity (0.952), specificity (0.922), PPV (0.924), NPV (0.951) and accuracy (0.937), can distinguish PHPT patients from healthy individuals. Furthermore, the Ca ∗ Cl/P ratio yielded a sensitivity of 0.831, specificity of 0.938, PPV of 0.931, NPV of 0.847 and accuracy of 0.885 for NPHPT.
CONCLUSIONS: The Ca∗Cl/P ratio provides excellent diagnostic power for diagnosis of PHPT, especially NPHPT.