Hypercalcemia of Malignancy and Acute Pancreatitis.

OBJECTIVES: Hypercalcemia of malignancy confers a poor prognosis. This systematic review evaluated published cases of hypercalcemia of malignancy presenting with acute pancreatitis (AP), in terms of clinical presentation and outcomes. METHODS: A comprehensive review of PubMed and Embase until March 18, 2020, was conducted. Studies were included if they reported on patients with hypercalcemia of malignancy and AP with attempts to exclude other etiologies of hypercalcemia and AP. Two independent reviewers selected and appraised studies using the Murad tool. RESULTS: Thirty-seven cases were identified. Mean (standard deviation) age was 44.8 (2.46) years. Mean (standard deviation) presenting corrected calcium was 14.5 (0.46) mg/dL. Parathyroid carcinoma (21.6%) and multiple myeloma (21.6%) were the most common malignancies. Cases were classified as severe (37.8%), mild (21.6%), and moderately severe (18.9%), whereas 21.6% did not report severity. Necrotizing pancreatitis developed in 21.6% of cases. Most cases were treated with intravenous hydration and bisphosphonates or calcitonin/calcitonin analogues. Mortality was 32.4% during the same presentation of AP. Among mortality cases, 10 of 12 had severe AP, and 5 of 12 had necrotizing pancreatitis. Degree of hypercalcemia did not influence mortality. CONCLUSION: Acute pancreatitis associated with hypercalcemia of malignancy is rare. One in 3 patients with this presentation may not survive AP.

Hypercalcemia caused by humoral effects and bone damage indicate poor outcomes in newly diagnosed multiple myeloma patients.

BACKGROUND: Hypercalcemia of malignancy (HCM) is a serious metabolic complication, and the highest rates are in multiple myeloma (MM). The cause of hypercalcemia in newly diagnosed multiple myeloma (NDMM) remains unknown. We sought to evaluate the prognostic impact and mechanism of hypercalcemia in patients with symptomatic NDMM. METHODS: We studied all consecutive MM patients who were initially diagnosed and followed up at Beijing Jishuitan Hospital between February 2013 and December 2019; 357 patients were included in the retrospective analysis. RESULTS: A total of 16.8% of MM patients presented with hypercalcemia at the time of MM diagnosis. The presence of hypercalcemia was associated with higher serum levels of ß2 microglobulin, creatinine, phosphorus, uric acid, procollagen I N-terminal peptide, ß-carboxy-terminal cross-linking telopeptide of type I collagen and osteocalcin, lower serum levels of hemoglobin, parathyroid hormone (PTH), and advanced ISS and R-ISS stages. Multivariate analysis showed that serum PTH, hemoglobin, creatinine, and uric acid levels were the main factors affecting hypercalcemia. The presence of hypercalcemia was associated with significantly inferior survival (40 months vs 57 months, p < 0.05) based on univariate analysis, and it remained an independent poor prognostic factor (HR: 1.854, 95% CI: 1.006-3.415, adjusted p = 0.048) in a multivariate model that included age and R-ISS stage. CONCLUSION: This study shows that hypercalcemia is associated with poor survival and is caused by manifold factors with humoral effects and local bone destruction.

Dose-intensive regimen treatment for small-cell carcinoma of the ovary of hypercalcemic type (SCCOHT).

PURPOSE: Small cell carcinoma of the ovary of hypercalcemic type (SCCOHT) is a rare and rapidly lethal disease affecting young women. Cytoreductive surgery associated with chemotherapy followed by a high dose chemotherapy regimen (HDC) demonstrated improved outcomes in a unique prospective and several retrospective studies, and this report aimed to confirm these results in an independent and larger cohort. METHODS: Between 2006 and 2018, we conducted a multicentric prospective study on 44 women diagnosed with SCCOHT. Patients were treated homogeneously with optimal cytoreductive surgery and chemotherapy protocol for four to six cycles (PAVEP). In case of complete response, patients received HDC with stem-cell support, followed by pelvic radiotherapy. The primary endpoint was the event-free survival (EFS) in the per-protocol cohort. Secondary analysis explored the effect of HDC with outcomes. RESULTS: Mean age at diagnosis was 33 years old (range 13.8-75.8). 14 patients presented with stage FIGO I, 21 with stage III and 9 with stage IV. Median follow-up was 53.4 months. 38 patients underwent optimal surgery with up to 6 cycles of PAVEP. 30 received HDC, and 21 pelvic radiotherapy. 21 relapses were reported leading to death for 18 patients. Median EFS in the per-protocol cohort was 18.2 months, and 2-year EFS rate was 40%. HDC was significantly associated with better overall survival (p < .001). Grades 3/4 adverse events were frequent but, in most cases, manageable, although one grade-5 adverse-event occurred during HDC. CONCLUSION: Intensive regimen containing multidrug chemotherapy, HDC and pelvic radiotherapy, for the management of SCCOHT, demonstrated encouraging survival and should be proposed for all patients. However, the significant toxicity cost associated is of concern and it should be restricted to expert centers.

Increased Risk of Infection-Related and All-Cause Death in Hypercalcemic Patients Receiving Hemodialysis: The Q-Cohort Study.

Although hypercalcemia is a risk factor for all-cause mortality in hemodialysis patients, it remains unknown whether hypercalcemia increases the risk of infection-related death. A total of 2869 hemodialysis patients registered in the Q-Cohort Study, a multicenter, prospective cohort study of hemodialysis patients, were analyzed. The predictor was albumin-corrected serum calcium level at baseline. The main outcome was infection-related death. Death risk were estimated by multivariable-adjusted Cox proportional hazard risk models and competing risk models. During the follow-up period of 4 years, 107 patients died of infection and 473 died of any cause. The patients were divided into four groups by the serum calcium level at baseline (G1, 5.7-8.9 mg/dL; G2, 9.0-9.4 mg/dL; G3, 9.5-9.9 mg/L; G4 10.0-16.5 mg/dL). In the multivariable-adjusted model, the incidence of infection-related death was significantly higher in the highest serum calcium group (G4) compared with the lowest serum calcium group (G1): hazard ratio [95% confidence interval], 2.34 [1.35-4.04], P = 0.002. Furthermore, higher serum calcium level was significantly associated with increased risk of all-cause death. In conclusion, our data suggest that a higher serum calcium level may be a risk factor for infection-related and all-cause death in hemodialysis patients.

Hypercalcemia at diagnosis of diffuse large B-cell lymphoma is not uncommon and is associated with high-risk features and a short diagnosis-to-treatment interval.

Diffuse large B-cell lymphoma (DLBCL) is an aggressive type of non-Hodgkin lymphoma. The prevalence of hypercalcemia in this neoplasm and its prognostic significance is unclear. We retrospectively evaluated the prevalence of hypercalcemia at diagnosis of DLBCL and explored associations of hypercalcemia with clinical factors and outcome. Outcome was assessed using event-free survival at 24 months (EFS24). A total of 305 patients (248 de novo DLBCL and 57 transformed indolent lymphomas) diagnosed between 2006 and 2018 in Reims were analyzed. The prevalence of calcemia >10.5 mg/dL at diagnosis of de novo DLBCL and transformed indolent lymphomas was 23% and 26%, respectively. Hypercalcemia in de novo DLBCL was strongly associated with high-risk features, especially with International Prognostic Index (IPI) components, but also with B symptoms, ß2-microglobulin, hemoglobin, and albumin levels. The diagnosis-to-treatment interval was significantly shorter for hypercalcemic patients (P = .001). These associations with adverse prognostic factors translated into lower rates of EFS24 (HR = 1.66; 95% CI, 1.08-2.54) and shorter PFS (P = .0059) and OS (P = .0003) for patients with lymphoma-related hypercalcemia but not independently of IPI parameters. These data suggest that hypercalcemia is rather a biomarker of the underlying biological aggressiveness of DLBCL.

Impact of Changes in Serum Calcium Levels on In-Hospital Mortality.

Background and objectives: Calcium concentration is strictly regulated at both the cellular and systemic level, and changes in serum calcium levels can alter various physiological functions in various organs. This study aimed to assess the association between changes in calcium levels during hospitalization and mortality. Materials and Methods: We searched our patient database to identify all adult patients admitted to our hospital from January 1st, 2009 to December 31st, 2013. Patients with ≥2 serum calcium measurements during the hospitalization were included. The serum calcium changes during the hospitalization, defined as the absolute difference between the maximum and the minimum calcium levels, were categorized into five groups: 0-0.4, 0.5-0.9, 1.0-1.4, 1.5-1.9, and ≥2.0 mg/dL. Multivariable logistic regression was performed to assess the independent association between calcium changes and in-hospital mortality, using the change in calcium category of 0-0.4 mg/dL as the reference group. Results: Of 9868 patients included in analysis, 540 (5.4%) died during hospitalization. The in-hospital mortality progressively increased with higher calcium changes, from 3.4% in the group of 0-0.4 mg/dL to 14.5% in the group of ≥2.0 mg/dL (p < 0.001). When adjusted for age, sex, race, principal diagnosis, comorbidity, kidney function, acute kidney injury, number of measurements of serum calcium, and hospital length of stay, the serum calcium changes of 1.0-1.4, 1.5-1.9, and ≥2.0 mg/dL were significantly associated with increased in-hospital mortality with odds ratio (OR) of 1.55 (95% confidence interval (CI) 1.15-2.10), 1.90 (95% CI 1.32-2.74), and 3.23 (95% CI 2.39-4.38), respectively. The association remained statistically significant when further adjusted for either the lowest or highest serum calcium. Conclusion: Larger serum calcium changes in hospitalized patients were progressively associated with increased in-hospital mortality.

Hospital mortality and long-term mortality among hospitalized patients with various admission serum ionized calcium levels.

BACKGROUND: We conducted a single-center historical cohort study to evaluate the association between admission serum ionized calcium and mortality in hospitalized patients. METHODS: We included hospitalized patients from January 2009 to December 2013 who had available serum ionized calcium at the time of admission. We assessed the in-hospital and 1-year mortality risk based on admission serum ionized calcium using multivariate logistic and Cox proportional hazard analysis, respectively. To test non-linear association, we categorized serum ionized calcium into six groups; ≤4.39, 4.40-4.59, 4.60-4.79, 4.80-4.99, 5.00-5.19, ≥5.20 mg/dL and selected serum ionized calcium of 4.80-4.99 mg/dL as a reference group. RESULTS: We studied a total of 33,255 hospitalized patients. The mean admission serum ionized calcium at 4.8 ± 0.4 mg/dL. Hospital and 1-year mortality observed in 1,099 (3%) and 5,239 (15.8%), respectively. We observed a U-shaped association between admission serum ionized calcium and in-hospital and 1-year mortality. Ionized calcium lower threshold for increased in-hospital and 1-year mortality rates was ≤4.59 and ≤4.39 mg/dL, respectively. Ionized calcium upper threshold for increased in-hospital and 1-year mortality rates was ≥5.20 mg/dL. CONCLUSION: Both hypocalcemia and hypercalcemia were associated with increased short- and long-term mortality with a U-shape relationship.

Hypercalcemia is associated with a poor prognosis in lymphoma a retrospective monocentric matched-control study and extensive review of published reported cases.

The prognostic significance of hypercalcemia in lymphoma has only been studied on small series to date. We conducted a retrospective, monocentric, matched-control study that aimed to compare the outcome of patients diagnosed with any histological subtype of lymphoma associated with hypercalcemia, at diagnosis or relapse, with a group of controls matched for histological and prognostic factors. Sixty-two and 118 comparable patients treated between 2000 and 2016 were included in hypercalcemia and control cohorts, respectively. Hypercalcemia was found mainly at diagnosis (71%) in higher-risk patients (prognosis scores ≥ 3, 76%) and those with diffuse large B cell lymphoma (67.7%), stage III/IV disease (91.9%), and elevated LDH (90.3%). Two-year progression-free survival (PFS) was shorter in the hypercalcemia than control cohort [30.1% (95% confidence interval (95% CI) 18.3-41.9) vs 63.9% (95% CI 5.1-72.7), p < 0.001]. Two-year overall survival (OS) was 40.6% (95% CI 28.1-53.1) and 77.7% (95% CI 70.1-85.3) in the hypercalcemia and control cohorts, respectively (p < 0.001). Hypercalcemia was independently associated with poor PFS [HR = 2.5 (95% CI 1.4-3.5)] and OS [HR = 4.7 (95% CI 2.8-7.8)] in multivariate analysis. Among the 40 patients who received autologous stem cell transplantation (ASCT), hypercalcemia was still associated with shorter OS [2-year OS: 65% (95% CI 40.1-89.9) vs 88.0 (95% CI 75.3-100), p = 0.04]. Hypercalcemia may be associated with chemo-resistance, given its impact on PFS and OS. Hence, these data suggest that alternate strategies for lymphoma patients with hypercalcemia should be developed.

Outcomes of hypercalcemia of malignancy in patients with solid cancer: a national inpatient analysis.

Hypercalcemia of malignancy (HCM) is present in one-third of cancer patients and is associated with a significant mortality risk of 50% within 1 month of diagnosis. We aimed to study the impact and outcomes of HCM in hospitalized patients with solid cancer. We analyzed data captured in the National Inpatient Sample database of the Agency of Healthcare Research and Quality. The study included all hospitalizations in adult solid cancer patients between January 2012 and September 2015 with hypercalcemia. All encounters associated with HCM were identified using the ICD-9 code (275.42) for hypercalcemia. Encounters with other known causes of hypercalcemia were excluded. The co-primary outcomes were incidence of HCM and inpatient mortality. During the study period, 7,501,209 hospitalizations met our inclusion criteria. Approximately 1.7% (n = 126,875) of these hospitalizations were related to HCM. This corresponds to approximately 1 in 59 solid malignancy associated hospitalizations. The mean age of patients with HCM was 65.7 years; 49% were females; 69% were Caucasians; 73% had metastatic disease and 22% received a palliative care consult. When compared to those without HCM, those hospitalized with HCM had a significantly longer mean hospital length of stay (7.3 days vs. 5.6 days, p < 0.001), higher inpatient mortality (12.3% vs. 5.5%, adjusted OR 1.76 (95% CI 1.69-1.84), p < 0·0001), and a greater likelihood of discharge to other facilities (27.4% vs. 16.2%, p < 0.0001). Although HCM accounts for < 2% of all hospitalizations in patients with solid cancer, those with HCM display higher mortality than those without HCM.

Intensive care unit admission in patients with T cell lymphomas: clinical features and outcome.

T cell non-Hodgkin lymphomas (T-NHLs) are aggressive malignancies which have a high risk of life-threatening complications. However, their prognosis in the intensive care unit (ICU) setting has not yet been assessed. We conducted a study including 87 ICU patients either with newly diagnosed T-NHLs or those undergoing first-line therapy admitted between January 1, 2000, and December 31, 2014. The primary subtypes were peripheral T cell lymphoma (PTCL) (n = 41, 47%), anaplastic large-cell lymphoma (ALCL) (n = 13, 15%), and adult T-leukaemia/lymphoma (ATLL) (n = 11, 13%). Six in every ten patients had malignancy-related complications (haemophagocytic syndrome 37%, tumour lysis syndrome 18% and hypercalcaemia 9%), while infections accounted for one quarter of ICU admissions. Nine fungal infections were documented, including six invasive aspergillosis. Urgent chemotherapy was started in the ICU in 59% of the patients, and urgent surgery was required in 13%. ICU and day-90 mortality were 22% and 41%, respectively. Multivariate analysis showed that SOFA score at day 1, age, sepsis and haemophagocytic syndrome were independent predictors of day-90 mortality. Compared to 66 ICU-matched controls with non-Hodgkin B cell lymphomas, patients with T-NHLs had a similar ICU survival. Overall survival rates of patients with T cell NHLs and B cell NHLs were 20% and 46%, respectively (hazard ratio for death associated with T cell NHLs 2.00 [1.12-3.58]). Patients with T cell NHLs had a very poor long-term outcome. Although the high rate of short-term survival suggests that an ICU trial is a reasonable option for patients newly diagnosed for the malignancy, extended stay in the ICU or further readmission should be considered only for highly selected patients who respond to the haematological treatment.

The Use of Low-Calcium Hemodialysis in the Treatment of Hypercalcemic Crisis.

BACKGROUND: We reviewed the results of low-calcium hemodialysis (LCHD; 1.25 mmol/L) in the treatment of 42 cases admitting with hypercalcemic crisis. METHODS: All patients (≥18 years) who started LCHD due to hypercalcemia between 2002 and 2017 were retrospectively analyzed. Biochemical data were obtained at the beginning of the first hemodialysis and at the end of the last hemodialysis. -"Refractory" cases were defined as patients having albumin corrected serum total calcium (SCatotal) levels above 10.2 mg/dL despite of all medical, surgical, and hemodialysis treatments. RESULTS: By acceptance of 3 cases admitted again over 6 months as new cases, a total of 42 cases (male, 57.1%) with a mean age of 55.9 ± 14.8 years underwent urgent hemodialysis. Most of the patients (82.1%) had malignancies. The mean SCatotal level at the beginning of hemodialysis sessions was 15.89 ± 2.53 mg/dL. The mean decline of SCatotal level was 4.63 ± 2.72 mg/dL. Refractory cases received hemodialysis after admission significantly later than improved cases (48 [interquartile ranges (IQR) 24-168] vs. 24 [IQR 12-48] h, p = 0.010). Serum creatinine and SCatotal levels at the last visit were significantly more in refractory cases than improved cases (1.92 [IQR 0.81-3.41] vs. 1.30 [IQR 0.8-1.7] mg/dL, p = 0.031 and 12.43 ± 2.53 vs. 8.86 ± 0.67 mg/dL, p = 0.000 respectively). Mortality was significantly higher in refractory cases than improved cases (58.8 vs. 10.5%, p = 0.002). Overall mortality rate was 33.3%. CONCLUSION: Hypercalcemic crisis is a life-threatening condition and should be managed immediately.

Association between Extreme Values of Markers of Chronic Kidney Disease: Mineral and Bone Disorder and 5-Year Mortality among Prevalent Hemodialysis Patients.

BACKGROUND/AIMS: We examined the association between markers of chronic kidney disease - mineral and bone disorder (CKD-MBD) and mortality in hemodialysis (HD) patients. METHODS: We retrospectively reviewed the association between markers of CKD-MBD and mortality in 1,126 HD patients from 2009 to 2013 with baseline (B), time-average (TA), and time-dependent (TD) Cox regression models. RESULTS: Hypercalcemia (10.9-11.9 mg/dL) indicated an increased risk of all-cause mortality (TA: hazard ratio [HR] 3.49; p = 0.01). Hypophosphatemia (2.0-2.5 mg/dL) was significantly associated with an increased risk of all-cause mortality (TA: HR 5.18; p = 0.01). Hypophosphatemia (<2.0 mg/dL) was significantly associated with an increased risk of cardiovascular mortality in all models. Intact parathyroid hormone levels <60 and >1,500 pg/mL indicated an increased risk of all-cause mortality (TA: HR 1.64; p = 0.02; TD: HR 2.26; p = 0.02). CONCLUSION: Extreme values of CKD-MBD markers are associated with mortality risk in HD patients. Video Journal Club 'Cappuccino with Claudio Ronco' at http://www.karger.com/?doi=478972.

Calcium levels on admission and before discharge are associated with mortality risk in hospitalized patients.

AIM: Investigate the association of calcium levels on admission and change in levels during hospitalization with hospitalization outcomes. METHODS: Historical prospective data of patients hospitalized to units of internal medicine between 2011 and 2013. Albumin-corrected-calcium levels were classified to marked hypocalcemia (<7.5 mg/dL), mild hypocalcemia (7.5-8.5 mg/dL), normal calcium (8.5-10.5 mg/dL), mild hypercalcemia (10.5-11.5 mg/dL), marked hypercalcemia (>11.5 mg/dL). Main outcomes were length-of-hospitalization, in-hospital and long-term mortality. RESULTS: Cohort included 30,813 patients (mean age 67 ± 18 years, 51% male). Follow-up (median ± standard deviation) was 1668 ± 325 days. Most patients had normal calcium on admission (93%), 3% had hypocalcemia, 3% had hypercalcemia. Common causes for marked hypercalcemia were malignancy (56%) and hyperparathyroidism (22%). Last calcium levels before discharge or death were normal in 94%, with similar rates of hypercalcemia or hypocalcemia (3% each). Compared to in-hospital mortality with normal calcium on admission (6%), mortality was higher with mild (8%) and marked hypocalcemia (11%), and highest with mild (18%) and marked hypercalcemia (22%). Mortality rate at the end of follow-up was 48% with normal calcium or mild hypocalcemia, 51% with marked hypocalcemia, 68 and 79% with mild and marked hypercalcemia, respectively. Patients with normal calcium on admission and before discharge had the best prognosis. Hypercalcemia on admission or before discharge was associated with a 70% mortality risk at the end of follow-up. Normalization of admission hypercalcemia had no effect on long-term mortality risk. CONCLUSIONS: Abnormal calcium on admission is associated with increased short-term and long-term mortality. The excess mortality risk is higher with hypercalcemia than hypocalcemia. Calcium normalization before discharge had no effect on mortality.

The Effect of Suppressed Levels of Uninvolved Immunoglobulins on the Prognosis of Symptomatic Multiple Myeloma.

OBJECTIVE: The majority of multiple myeloma (MM) patients have high levels of monoclonal immunoglobulin in the serum and/or urine and suppressed levels of the uninvolved immunoglobulins. The prognostic significance of this phenomenon has not been assessed sufficiently. In this study, our aim is to evaluate the prognostic significance of uninvolved immunoglobulin suppression measured by nephelometry in patients with new symptomatic MM and the association with other features of the disease. MATERIALS AND METHODS: Between August 2003 and February 2015, 137 patients who were referred for the treatment of newly diagnosed symptomatic myeloma to the Hematology Department polyclinics of the Istanbul University Istanbul Faculty of Medicine were prospectively included and had available pretreatment immunoglobulin levels measured by nephelometry. RESULTS: Suppression of at least one uninvolved immunoglobulin was observed in 87% of patients and this situation was slightly more common in patients with immunoglobulin A myeloma but had no statistical significance (p>0.05). Uninvolved immunoglobulin suppression was also more common among patients who had bone marrow plasma cell infiltration of ≥40% and presented with anemia and hypercalcemia (p<0.05). The overall survival time was shorter in patients with positive calcium-renal-anemia-bone criteria and International Staging System stage 3 compared with others (p<0.05). Factors that were independently associated with inferior survival in the multivariate analysis included patients with estimated glomerular filtration rate of <60 mL/min, age of >65 years, lactate dehydrogenase of >300 IU/L, bone marrow plasma cells of ≥40%, and ß2-microglobulin of >3.5 mg/dL (p<0.05). CONCLUSION: In this study, 13.1% of MM patients had preserved levels of uninvolved immunoglobulins. We observed that patients who had preserved uninvolved immunoglobulin levels had better treatment responses and better pathologic signs, but statistical significance could not be shown. Conversely, patients with suppression of even one of the uninvolved immunoglobulins had a shorter survival, but similarly, statistical significance could not be shown.

Prevalence of hypercalcemia among cancer patients in the United States.

Hypercalcemia of malignancy (HCM) is a serious metabolic complication whose population-based prevalence has not been quantified. Rates of HCM differ by tumor type, with highest rates reported in multiple myeloma and lowest among colorectal and prostate cancer patients. This analysis estimates HCM prevalence in the US. This retrospective study used the Oncology Services Comprehensive Electronic Records (OSCER) warehouse of electronic health records (EHR) including laboratory values from 569000 patients treated at 565 oncology outpatient sites. OSCER data were projected to the national level by linking EHR to claims data. Cancer patients included were ≥18 years, and had serum calcium (Ca) and albumin (for corrected serum Ca [CSC]) records. Period prevalence was estimated by HCM CTCAE grade, tumor type, and year (2009-2013). Estimates were adjusted to capture patients diagnosed with HCM outside oncology practices based on a subset of patients linkable to office and hospital data. The analysis included 68023 (2009) to 121482 (2013) cancer patients. In 2013, patients with HCM had a median of six Ca tests, 69.7% had chemotherapy, and 34% received bone modifying agents. HCM rates were highest for multiple myeloma patients (7.5% [2012]-10.2% [2010]), lowest for prostate cancer (1.4% [2012]-2.1% [2011]).The estimated adjusted annual prevalence of HCM from 2009 to 2013 was 95441, 96281, 89797, 70158, and 71744, respectively. HCM affected 2.0-2.8% of all cancer patients. EHR data from oncology clinics were critical for this study because these data contain results from laboratory studies (i.e., serum calcium values) that are routinely ordered in that setting. We estimated that the prevalence of HCM in the US in 2013 is 71744, affecting approximately 2% of cancer patients overall. This percentage differs by tumor type and appears to have decreased over the five-year study period.

Hidden Hypercalcemia and Mortality Risk in Incident Hemodialysis Patients.

CONTEXT: Neither uncorrected- nor albumin-corrected total calcium reliably predict ionized calcium in patients with end-stage renal disease. However, little is known about the consequences of inaccurate assessment of calcium concentration using total calcium. OBJECTIVE: We hypothesized that hidden hypercalcemia (ie, elevated ionized calcium with normal total calcium) and apparent hypercalcemia (ie, elevated ionized calcium with elevated total calcium) are both associated with increased mortality risk. DESIGN, SETTING, AND PATIENTS: We identified 874 incident hemodialysis patients with measured serum ionized calcium, total calcium, albumin, phosphorus, and bicarbonate from October 2007 to December 2011, using data from a large dialysis organization in the United States. EXPOSURES: Serum concentrations of ionized calcium and total calcium were measured. MAIN OUTCOME MEASURE: The primary outcome was all-cause mortality. RESULTS: There was only fair interindex agreement with calcium status between ionized calcium and uncorrected or corrected total calcium (κ = 0.32 and 0.27, respectively). Among patients with high ionized calcium (>1.32 mmol/liter), 88% and 70% patients were incorrectly categorized as being normocalcemic using uncorrected and corrected total calcium, respectively, and were thus considered to have "hidden hypercalcemia." Compared to patients with low-normal ionized calcium (1.16-1.24 mmol/liter), patients with high ionized calcium had a significantly higher mortality risk (adjusted hazard ratio, 1.77; 95% confidence interval, 1.13-2.75). Furthermore, compared to patients with normocalcemia (ionized calcium 1.16-1.32 mmol/liter), those with hidden hypercalcemia by uncorrected and corrected total calcium also had a higher risk for death (adjusted hazard ratio 1.75 [95% confidence interval 1.11-2.75] and 1.80 [95% confidence interval, 1.11-2.90], respectively). CONCLUSION: The majority of end-stage renal disease patients with elevated ionized calcium are incorrectly categorized as normocalcemic using conventional total calcium measurements; these patients have a higher death risk. Future research is needed to establish whether reducing ionized calcium concentrations in these patients improves clinical outcomes.

Clinical features and survival of 338 multiple myeloma patients treated with hematopoietic stem cell transplantation or conventional chemotherapy.

Therapeutic approaches against multiple myeloma (MM) have largely changed during the past decade. Hematopoietic stem cell transplantation (HSCT) and licensing of immunomodulators and proteasome inhibitors have resulted in better response and increased overall survival rates compared to previous conventional therapies. To assess the impact that these new strategies have had on outcome of patients with symptomatic MM in Spain, we conducted an epidemiological retrospective analysis of 338 newly diagnosed patients with stage II-III MM who started first-line treatment over a 2-yr period (2003-2005) by collecting data from their medical records. Most patients had been diagnosed with secretory MM (94.4%), 41.7% stage II and 58.3% stage III. The presence of bone lesions (72.2%), as well as anemia (79.8%) and elevated beta2-microglobulin levels (62.3%), was a common finding; in contrast, hypercalcemia and elevated serum creatinine were less frequent (25% each). First-line treatment had consisted of either conventional chemotherapy (62%) or induction treatment plus autologous HSCT (38%), as per standard clinical practice. HSCT not only resulted in greater objective response rates (93% vs. 50%), but also contributed to a significant increase in 3-yr survival (85% vs. 49.7%; 95% CI, range 77-91 vs. 41-58; P < 0.001). Overall, 55% of patients presented treatment-related adverse events, mainly hematological. Toxicity rates were higher among patients treated with alkylating-based regimens and in those undergoing transplantation. In conclusion, data analysis shows an adequate balance between increased response rates and safety that supports the use of up-front high-dose HSCT therapy in younger patients. Most importantly, this study provides further confirmation that the introduction of HSCT has significantly prolonged survival of patients with MM.

Clinical analysis of 64 patients with lung-cancer-associated hypercalcemia.

OBJECTIVE: This study investigated the factors influencing survival time of patients with lung-cancer-associated hypercalcemia. DATA AND METHODS: A total of 64 pathologically confirmed patients with Stage IV lung-cancer-associated hypercalcemia were enrolled from Beijing Hospitals between August 2010 and July 2015. Clinical materials included patients' gender, age, pathological type, highest albumin-corrected calcium level, serum alkaline phosphatase level, creatinine clearance rate, organ (bone, liver, brain, and adrenal gland) metastasis, number of distal metastatic sites, and survival time after diagnosis of hypercalcemia. Univariate and multivariate analyses were performed to screen the risk factors affecting patients' survival. RESULTS: Albumin-corrected calcium levels of the 64 patients ranged from 2.56 to 4.57 mmol/L, and the median value was 2.76 mmol/L. Survival time after diagnosis of hypercalcemia varied from 1 to 1340 days, and the median survival time was 104 days. Univariate analysis showed that gender, age (>60-year-old), albumin-corrected calcium levels, elevation of alkaline phosphatases, brain metastasis, and number of distal metastatic sites were predictors for poor survival (P = 0.026, P = 0.022, P < 0.001, P = 0.043, P = 0.041, P = 0.003). In Cox proportional hazard model analysis, corrected hypercalcemia levels and alkaline phosphatase levels were determined to be risk factors affecting patients' survival time (hazard ratio [HR] = 6.828, P = 0.000; HR = 1.957, P = 0.026). CONCLUSIONS: Patients with Stage IV lung-cancer-associated moderate and severe hypercalcemia exhibited shorter survival time and poor prognosis. After correction, moderate and severe elevations of hypercalcemia and abnormal elevation of alkaline phosphatase levels were shown to be significant factors shortening patients' survival time.

Quality and Outcomes of Treatment of Hypercalcemia of Malignancy.

Using a nationwide database, 4,874 patients with hypercalcemia of malignancy were identified. The in-hospital mortality rate was 6.8%. Overall, 1,971 (40.4%) patients received pamidronate and 1,399 (28.7%) received zoledronic acid during hospitalization. Calcitonin was utilized in 1,337 (27.4%) patients while glucocorticoids were administered to 1,311 (26.9%). Use of contraindicated medications was noted in 136 (2.8%) patients who received thiazide diuretics and 12 (0.2%) who received lithium. Tumor site, presence of bone metastases, and severity of illness were predictors of treatment. There was no association between treatment with bisphosphonates, calcitonin, or glucocorticoids and morbidity or mortality.

PTHrP-mediated hypercalcemia: causes and survival in 138 patients.

CONTEXT: Hypercalcemia is a common complication of cancer with PTHrP an important mediator. Literature on the underlying causes of PTHrP-mediated hypercalcemia, in both malignant and benign conditions, is limited to small case series and case reports. OBJECTIVE: The purpose of this study was to systematically identify a large series of cases of PTHrP-mediated hypercalcemia and to document differences in demographics and the clinical course between malignant and benign etiologies. DESIGN, SETTING, AND PATIENTS: This was a hospital-based, retrospective case series that identified subjects from 1999 to 2010 from the public hospital system in Queensland, Australia. Included subjects were 18 years and older and had persistent hypercalcemia with simultaneously elevated PTHrP. RESULTS: A total of 138 cases were identified. Solid organ malignancies made up 82.6% (n = 114) of cases, with squamous cell carcinoma (28.2% of total) and adenocarcinomas (27.5%) almost equally as common. Hematological malignancy and benign conditions made up 8.7% (n = 12) each. Squamous cell carcinoma of the lung was the single most commonly identified etiology (10.9%). Causes not previously identified included myxoid sarcoma, plasma cell leukemia, duodenal adenocarcinoma, metastatic Merkel cell carcinoma, and epithelioid hemangioendothelioma. Median survival was different among the groups (52 days [interquartile range, 21-132 days] for solid organ malignancy, 362 days [18-652 days] for hematological malignancy, and 906 days [16 days to undefined] for the apparently benign group; P < .0001). There were no differences in PTHrP among the groups. Although the mean corrected calcium level was lower in the benign group (3.03 mmol/L [2.80-3.29 mmol/L]) compared with that in the solid organ (3.11 mmol/L [2.89-3.46 mmol/L]) and hematological malignancy groups (3.60 mmol/L [3.01-3.79 mmol/L]) groups (P = .046), it was not a useful discriminator of etiology. CONCLUSION: PTHrP-mediated hypercalcemia is most frequently caused by solid organ malignancy, and it portends a poor prognosis. Although the solid organ malignancy group had the shortest survival, the hematological malignancy and apparently benign causes groups still had relatively short overall survival.