Related Events In Patients Research Articles

Adverse skeletal related events in patients with bone-metastatic pheochromocytoma/paraganglioma

Metastatic pheochromocytomas and paragangliomas (PPGLs) are frequently associated with skeletal complications.Primary objective: to describe the frequency of adverse skeletal related events (SREs) in PPGL patients with bone metastases (BMs). Secondary objectives: to 1) identify predictive and prognostic factors for SREs and 2) obtain information on the effectiveness of bone resorption inhibitors in reducing SRE risk and improving outcomes in term of survival and SREs time onset.In this retrospective multicenter, multinational study, 294 PPGL patients were enrolled.SREs occurred in 90 patients (31 %). Fifty-five patients (19 %) had bone fractures, 47 (16 %) had spinal cord compression, and 11 (4 %) had hypercalcemia. Twenty-two patients (7 %) had more than one SRE. Sixty-four patients (22 %) underwent surgery, and 136 (46 %) underwent radiotherapy. SREs occurred a median of 4.4 months after diagnosis of BM (range, 0–246.6 months). Independent factors associated with reduced risk of SREs in multivariable analysis were I-131-MIBG radionuclide therapy (hazard ratio [HR], 0.536 [95 % CI, 0.309–0.932]; P = .027) and absence of liver metastases (HR, 0.638 [95 % CI, 0.410–0.992]; P = .046). The median overall survival duration was 5.3 year. In multivariable analysis, age younger than 48 years at PPGL diagnosis (HR, 0.558 [95 % CI, 0.3877–0.806]; P = .002), absence of liver metastases (HR, 0.618 [95 % CI, 0.396–0.965]; P = .034), treatment with bisphosphonates or denosumab (HR, 0.598 [95 % CI, 0.405–0.884]; P = .010), and MIBG radionuclide therapy (HR, 0.444 [95 % CI, 0.274–0.718]; P = .001) were associated with a reduced risk of death.SREs occur frequently and early in bone-metastatic PPGL patients but do not negatively impact survival. MIBG radionuclide therapy and treatment with bone resorption inhibitors are associated with favorable outcome.

Bone metastases and skeletal related events in patients with gastrointestinal neuroendocrine tumors.

Bone metastases and skeletal related events in patients with gastrointestinal neuroendocrine tumors.

Retrospective analysis of the relationship between time to anti-resorptive therapy and incidence of skeletal related events in patients with multiple myeloma.

8048 Background: Patients with multiple myeloma (MM) often have bone disease at diagnosis and are at risk of developing skeletal related events (SRE) (pathological fractures, spinal cord compression, and/or need for radiotherapy or surgery to bone). It is well established that for patients with lytic bone lesions at diagnosis, the use of anti-resorptive agents lead to a lower incidence of SREs. However, it is common for initiation of anti-resorptive therapy to be delayed. Recent studies have demonstrated that anti-resorptive therapy is underutilized in patients with MM. However, the effect of time to initiation of anti-resorptive agent after diagnosis of MM on SREs has not been well studied. Herein, we conducted a multi-center retrospective analysis to determine if time to anti-resorptive agent has an adverse impact on the risk of SREs. Methods: We performed a retrospective cohort study using our Electronic Health Record system to identify patients with newly diagnosed MM between July 1st, 2016 and June 30th, 2019 at two large academic centers. Patients previously treated or patients not treated with anti-resorptive therapy were excluded. The study’s primary endpoint was hazard ratio of developing a SRE based on time to anti-resorptive therapy. The relationship between incidence of SREs and time to anti-resorptive therapy, gender, age, International Staging System (ISS) stage at diagnosis, and prior SRE present at diagnosis was analyzed by using a multivariable Cox proportional hazards model. The cutoff point of anti-resorptive therapy delay was based on the recursive partitioning of univariable Cox model. Results: 759 patients were included in the study (Thomas Jefferson University: n = 232; The Ohio State University: n = 527). Median age at diagnosis is 60.2 years (IQR: 12.4 years). 57% of patients were male. 77.9% and 20.3% of patients identified as white and black respectively. 210 patients (27.7%) were noted to have osteopenia, 45 (5.9%) had osteoporosis, 229 (30.2%) were vitamin D deficient, and 319 (42%) were obese at diagnosis. A skeletal related event was present at diagnosis in 338 (45.1%) of patients. 180 (34%) patients received anti-resorptive agents within 31 days. A delay in initiating anti-resorptive agents of greater than 31 days from diagnosis had an increased risk for SRE with a hazard ratio 1.654 (1.054~2.598; p-value: 0.029). Conclusions: This large multicenter retrospective study demonstrated that time to anti-resorptive therapy MM patients has a significant impact on the risk of SRE. Given many of the challenges in starting anti-resorptive therapy in a timely manner, this study emphasizes the need for inter-professional, multi-disciplinary collaborations to streamline the workflow and start therapy within the first month of diagnosis. Ongoing efforts are underway to develop quality improvement processes to achieve this goal.

Analysis of anesthesia related severe adverse events in congenital catheterization cases from a single institution.

Analysis of anesthesia related severe adverse events in congenital catheterization cases from a single institution.

SGLT-2 inhibitors and in-stent restenosis-related events after acute myocardial infarction: an observational study in patients with type 2 diabetes

BackgroundNo study evaluated the incidence of intra-stent restenosis (ISR)-related events in patients with type 2 diabetes (T2DM) and acute myocardial infarction (AMI) treated or not with sodium/glucose cotransporter 2 inhibitors (SGLT2i).MethodsWe recruited 377 patients with T2DM and AMI undergoing percutaneous coronary intervention (PCI). Among them, 177 T2DM were treated with SGLT2 inhibitors before PCI. The primary outcome was major adverse cardiovascular events (MACE) defined as cardiac death, re-infarction, and heart failure related to ISR. In patients without ISR, minimal lumen area and minimal lumen diameter were assessed by coronary CT-angiography at 1-year follow-up.ResultsGlycemic control was similar in SGLT2i-treated patients and never SGLT2i-users. The incidence of ISR-related MACE was higher in never SGLT2i-users compared with SGLT2i-treated patients, an effect independent of glycemic status (HR = 0.418, 95% CI = 0.241–0.725, P = 0.002) and observed also in the subgroup of patients with HbA1c < 7% (HR = 0.393, 95% CI = 0.157–0.984, P = 0.027). In patients without the event, the stent patency was greater in SGLT2i-treated patients compared with never SGLT2i-users at 1-year follow-up.ConclusionsSGLT2i treatment in T2DM is associated with a reduced incidence of ISR-related events, independently of glycemic control.

Incidence of Post-denosumab Rebound Hypercalcaemia in Bony-Metastatic Breast Cancer.

Denosumab reduces incidence of skeletal related events in patients with bony-metastatic breast cancer, however cessation is associated with a rebound phenomenon which, rarely, has been associated with hypercalcaemia. We aimed to identify the incidence of post-denosumab cessation rebound hypercalcaemia amongst patients with breast cancer-related bony metastases. We performed a single-centre retrospective cohort analysis to determine the incident of rebound hypercalcaemia amongst patients treated with antiresorptive agents for bony metastatic breast cancer between 2016-2020. 22,320 outpatient encounters were reviewed, which identified 97 patients with bonymetastatic disease treated with antiresorptive therapy. Of the 21 patients who had denosumab ceased, six (28.6%) developed hypercalcaemia. Interval between last denosumab dose and onset of hypercalcaemia was a median 7.5 (range 2-13) months. There was a significant difference in both denosumab treatment duration as well as total treatment dose exposure between patients who developed hypercalcaemia post-denosumab cessation (median 41 months, 40 doses) and those who remained normocalcaemic (median 10 months, 5 doses), p = 0.009. In our study, hypercalcaemia occurred between two and thirteen months after denosumab cessation. Greater denosumab treatment duration as well as total denosumab dose exposure was associated with higher risk of hypercalcaemia after denosumab cessation. Hormonal therapy or previous bisphosphonate treatment was not seen to impact upon development of hypercalcaemia. Rebound hypercalcaemia is a rare but important diagnosis to consider in patients experiencing hypercalcaemia after denosumab cessation.

Identification and Analysis of Gut Microbiota and Functional Metabolism in Decompensated Cirrhosis with Infection.

Intestinal dysbiosis play a role in the adverse outcomes of sepsis and septic shock. However, variations in bacterial diversity and microbiota-related functional metabolic alterations within the gut microbiome in decompensated cirrhosis (DC) patients with infection remain unknown. We conducted 16-srRNA sequencing on stool samples (n=51: sepsis, 27/no sepsis, 24) collected from consecutive DC patients upon admission. Bacterial diversity, significant taxa, and respective metabolic profiling were performed based on subgroup comparisons. Conet/Cytoscape was utilized to identify significant non-random patterns of bacterial copresence and mutual exclusion for clinical events. Genera associated with pathogenicity in conditions of immune exhaustion (Corynebacterium, Lautropia) were predominant in patients with sepsis. Metabolic pathways associated with oxidative stress and endotoxemia [lipopolysaccharide (LPS) synthesis and sulfur relay] were significantly upregulated in sepsis. Specific taxa were associated with sites of infection in DC patients. Protective oxidant pathways that increase glutathione were upregulated in those without sepsis. Gammaproteobacteria family of sulfur-metabolizing bacteria, exaggeration of orally predominant pathogens (Prevotella), and pathways of severe LPS-related hyperinflammatory stress were notable in those with interleukin-6 levels >1,000 pg/dL. Pathogenic genera related to an immune deficient state was significant in DC with ≥2 infection episodes. Megamonas was associated with survival during the same admission. Specific gut microbiota and their metabolites were associated with sepsis and related events in patients with DC. Identifying beneficial strains that reduce immune exhaustion and supplementation of favorable metabolites could improve therapeutics for DC and sepsis, for which larger prospective, well controlled population-based studies remain an unmet need.

Association Between Long-term Ambient PM2.5 Exposure and Cardiovascular Outcomes Among US Hemodialysis Patients

Ambient PM2.5 (particulate matter with a diameter of 2.5 microns) is a ubiquitous air pollutant with established adverse cardiovascular (CV) effects. However, quantitative estimates of the association between PM2.5 exposure and CV outcomes in the setting of kidney disease are limited. This study assessed the association of long-term PM2.5 exposure with CV events and cardiovascular disease (CVD)-specific mortality among patients receiving maintenance in-center hemodialysis (HD). Retrospective cohort study. 314,079 adult kidney failure patients initiating HD between 2011 and 2016 identified from the US Renal Data System. Estimated daily ZIP code-level PM2.5 concentrations were used to calculate each participant's annual average PM2.5 exposure based on the dialysis clinics visited during the 365 days before the outcome. CV event and CVD-specific mortality were ascertained based on ICD-9/ICD-10 diagnostic codes and recorded cause of death from Centers for Medicare & Medicaid Services form2746. Discrete time hazards models were used to estimate hazards ratios per 1 μg/m3 greater annual average PM2.5, adjusting for temperature, humidity, day of the week, season, age at baseline, race, employment status, and geographic region. Effect measure modification was assessed for age, sex, race, and baseline comorbidities. Each 1 μg/m3 greater annual average PM2.5 was associated with a greater rate of CV events (HR, 1.02 [95% CI, 1.01-1.02]) and CVD-specific mortality (HR, 1.02 [95% CI, 1.02-1.03]). The association was more pronounced for people who initiated dialysis at an older age, had chronic obstructive pulmonary disease (COPD) at baseline, or were Asian. Evidence of effect modification was also observed across strata of race, and other baseline comorbidities. Potential exposure misclassification and unmeasured confounding. Long-term ambient PM2.5 exposure was associated with CVD outcomes among patients receiving maintenance in-center HD. Stronger associations between long-term PM2.5 exposure and adverse effectswere observed among patients who were of advanced age, had COPD, or were Asian. Long-term exposure to air pollution, also called PM2.5, has been linked to adverse cardiovascular outcomes. However, little is known about the association of PM2.5 and outcomes among patients receiving dialysis, who are individuals with high cardiovascular disease burdens. We conducted an epidemiological study to assess the association between the annual PM2.5 exposure and cardiovascular events and death among patients receiving regular outpatient hemodialysis in the United States between 2011 and 2016. We found a higher risk of heart attacks, strokes, and related events in patients exposed to higher levels of air pollution. Stronger associations between air pollution and adverse health events were observed among patients who were older at the start of dialysis, had chronic obstructive pulmonary disease, or were Asian. These findings bolster the evidence base linking air pollution and adverse health outcomes and may inform policy makers and clinicians.

Risk factors and economic burden of postoperative anastomotic leakage related events in patients who underwent surgeries for colorectal cancer.

Nationwide research about the clinical and economic burden caused by anastomotic leakage (AL) has not been published yet in Korea. This study assessed the AL rate and quantified the economic burden using the nationwide database. This real world evidence study used health claims data provided by the Korean Health Insurance Review and Assessment Service (HIRA, which showed that 156,545 patients underwent anterior resection (AR), low anterior resection (LAR), or ultra-low anterior resection (uLAR) for colorectal cancer (CRC) between January 1, 2007 and January 31, 2020. The incidence of AL was identified using a composite operational definition, a composite of imaging study, antibacterial drug use, reoperation, or image-guided percutaneous drainage. Total hospital costs and length of stay (LOS) were evaluated in patients with AL versus those without AL during index hospitalization and within 30 days after the surgery. Among 120,245 patients who met the eligibility criteria, 7,194 (5.98%) patients had AL within 30 days after surgery. Male gender, comorbidities (diabetes, metastatic disease, ischemic heart disease, ischemic stroke), protective ostomy, and multiple linear stapler use, blood transfusion, and urinary tract injury were associated with the higher odds of AL. Older age, rectosigmoid junction cancer, AR, LAR, and laparoscopic approach were related with the reduced odds of AL. Patients with AL incurred higher costs for index hospitalization compared to those without AL (8,991 vs. 7,153 USD; p<0.0001). Patients with AL also required longer LOS (16.78 vs. 14.22 days; p<0.0001) and readmissions (20.83 vs. 13.93 days; p<0.0001). Among patients requiring resection for CRC, the occurrence of AL was associated with significantly increased costs and LOS. Preventing AL could not only produce superior clinical outcomes, but also reduce the economic burden for patients and payers.

Bone modifying agents and skeletal related events in patients with metastatic non-small cell lung cancer treated with immune checkpoint inhibitors.

e18593 Background: Bone metastases and skeletal related events (SREs) are a common cause of morbidity among patients with metastatic non-small cell lung cancer (mNSCLC). SREs include pathologic bone fractures, spinal cord compression, orthopedic surgery/stabilization, and palliative radiation to bone. Bone modifying agents (BMA) such as bisphosphonates and RANK ligand inhibitors are often used for mNSCLC patients with bone metastases to reduce the incidence of SRE. Data on the associations between BMA use and overall survival (OS) and the development of SRE among patients with mNSCLC treated with immune checkpoint inhibitors (ICI) is limited. Methods: We conducted a retrospective study of patients with mNSCLC treated with first line pembrolizumab or pembrolizumab plus chemotherapy at The Ohio State University from 2017-2020. The associations between SRE and categorical variables were studied using Fisher’s exact test and with continuous variables using the Kruskal-Wallis test. The association between BMA and risk of osseous progression was studied using Fisher’s exact test. The association between BMA and OS was examined using a Cox proportional hazard model. Median OS was estimated using the Kaplan-Meier method with 95% CI. OS was calculated from date of ICI initiation to death from any cause or last follow up. Results: We identified a cohort of 228 patients: 107 (47%) treated with pembrolizumab and 121 (53%) treated with pembrolizumab plus chemotherapy; 48 (21%) had squamous histology and 179 (79%) had nonsquamous histology (1 had NSCLC histology not specified); median age 62.6 years; median OS was 26.8 months (95% CI: 17.2 – 34.5 months). A total of 95/228 (42%) patients had bone metastases at time of ICI initiation; 45/95 (42%) had treatment with BMA and 50/95 (58%) were not treated with BMA. Among patients with bone metastases at time of ICI, 45 (42%) developed SRE after ICI initiation and BMA use was not associated with risk of SRE (p = 1). BMA use was not significantly associated with risk of osseous progression (p = 0.21). For patients with baseline bone metastases prior to ICI, the use of BMA was not associated with OS (p = 0.24); the type of BMA used (bisphosphonate vs RANK ligand inhibitor) was also not associated with OS (p = 0.13). Conclusions: In patients with metastatic NSCLC treated with first line pembrolizumab alone or with chemotherapy, bone modifying agents were not associated with OS, decreased risk of osseous progression, or development of SRE in patients with baseline bone metastases prior to ICI initiation. The type of BMA used was also not associated with survival. Further studies evaluating the utility and impact of BMA use in this patient population are needed.

Prone Positioning in Patients With Acute Respiratory Distress Syndrome and Other Respiratory Conditions: Challenges, Complications, and Solutions

Acute respiratory distress syndrome (ARDS) and respiratory failure are characterized by hypoxemia, i.e., low levels of blood oxygen. Infections such as influenza and COVID-19 can lead to ARDS or respiratory failure. Treatment is through supportive measures. In severe cases, patients receive oxygen through a ventilator and, when appropriate, are placed in a prone position for an extended period. A retrospective review of events submitted to the Pennsylvania Patient Safety Reporting System (PA-PSRS) identified 98 prone position–related events in patients with ARDS, respiratory failure, distress, and pneumonia from January 1, 2010, through June 30, 2020; 30 events were associated with COVID-19. Skin integrity injuries accounted for 83.7% (82 of 98) of the events. The remaining events, 16.3% (16 of 98), involved unplanned extubations, cardiac arrests, displaced lines, enteral feedings, medication errors, a dental issue, and posterior ischemic optic neuropathy.

Comparison of Denosumab Versus Intravenous (IV) Bisphosphonate Use for Hypercalcemia in Multiple Myeloma

Background Hypercalcemia (HC) is a frequent complication of multiple myeloma (MM) occurring in 20-30% of patients. This is often associated with renal dysfunction and both features are important myeloma defining events resulting in significant morbidity and mortality. Denosumab, a fully human monoclonal antibody that inhibits RANKL, has been evaluated in the prevention of skeletal related events in patients with newly diagnosed MM, as well as the treatment of bisphosphonate-refractory HC of malignancy (HCM). Cases of denosumab for HCM in MM patients with renal dysfunction have been described. Both denosumab and IV bisphosphonates (IVB) represent treatment options for HC in MM. We describe a comparison of patients with MM with HC who received denosumab vs IVBs. Methods We retrospectively identified patients age ≥18 with a diagnosis of MM with HC (corrected serum calcium level [CSC] &amp;gt;10.5 mg/dL). Patients were included if they received either denosumab or IVB (zoledronic acid [ZA] or pamidronate), between April 2016 and June 2020. The primary endpoint was complete response (CR), defined as normalization of CSC to less than 10.5 mg/dL. Secondary endpoints included HC relapse (CSC &amp;gt;10.5 mg/dL) and safety. Hypocalcemia was graded per CTCAE v5. Acute kidney injury (AKI) was defined using KGIDO criteria. Patients were followed-up for 56 days. Bivariate analyses were performed. Results A total of 40 patients were included with 18 in the denosumab group and 22 in the IVB group, of whom 15 (68%) received ZA and 7 (32%) received pamidronate. Baseline characteristics are described in Table 1. Patients with newly diagnosed MM composed 33% and 55% of the denosumab and IVB groups, respectively. All patients in the denosumab group received 120 mg except one who received 60 mg, while in the IVB group, dose reductions occurred in 5/15 patients who received ZA (median dose, 4 mg; range, 3.3-4) and 4/7 patients who received pamidronate (median dose, 60 mg; range, 30-90). Most patients received HC treatment as an inpatient (58% inpatient vs. 42% outpatient). A minority of patients had received IVBs in the past 90 days. The mean CSC was 12.5 mg/dL (standard deviation [SD], 1.40) and 13.3 mg/dL (SD, 2.39) in the denosumab and IVB groups, respectively. Baseline serum creatinine (SCr) was higher and creatinine clearance (CrCl) was lower in the denosumab group (median SCr, 2.06 vs. 1.24 mg/dL, p=0.048; median CrCl, 33 vs. 48 mL/min, p=0.048). The CR rate by day 3-4 was 92% and 94% in the denosumab and IVB groups, respectively (p=NS). HC relapse occurred in 2 (12%) and 6 (29%) patients in the denosumab and IVB groups, respectively (p=0.257). Incidence of grade 1 hypocalcemia was similar between groups; however, incidence of grade ≥2 hypocalcemia was higher in the denosumab group. Incidence of new AKI was 28% (5/18) in the denosumab group 23% (5/22) in the IVB group (p=0.71). No patients in the denosumab group received an additional dose of denosumab within 14 days of initial dose. Three patients in the IVB group received an additional dose of an IVB within 14 days of initial dose. One patient, who was in the denosumab group, had refractory hypercalcemia and had not achieved CR at day 56. Conclusions We describe our experience with denosumab and IVB for the management of HC in patients with MM. The CR rate at 3-4 days was similar with either agent in our MM only population that was not bisphosphonate refractory. A higher incidence of grade 2 hypocalcemia was noted in the denosumab group. Conclusions on renal safety are limited by the small sample size and that patients in the denosumab group had a higher SCr on presentation. Denosumab and IVB represent acceptable agents for the management of HC in MM patients with further investigation necessary in those with renal dysfunction. Disclosures Lei: Fresenius Kabi USA: Consultancy; Trapelo Health: Consultancy; Bluebird Bio: Current equity holder in publicly-traded company; Bristol Myers Squibb: Current equity holder in publicly-traded company; Clovis Oncology: Current equity holder in publicly-traded company; Blueprint Medicines: Divested equity in a private or publicly-traded company in the past 24 months. Lou:Fresenius Kabi USA: Consultancy. Raje:Bluebird, Bio: Consultancy, Research Funding; Takeda: Consultancy; Immuneel: Membership on an entity's Board of Directors or advisory committees; Caribou: Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy; BMS: Consultancy; Celgene: Consultancy; Janssen: Consultancy; Karyopharm: Consultancy; Astrazeneca: Consultancy. Yee:Karyopharm: Consultancy; Oncopeptides: Consultancy; Sanofi: Consultancy; Takeda: Consultancy, Research Funding; Janssen: Consultancy; BMS: Consultancy, Research Funding; GlaxoSmithKline: Consultancy; Amgen: Consultancy, Research Funding; Celgene: Consultancy, Research Funding. OffLabel Disclosure: Denosumab is indicated for the treatment of hypercalcemia of malignancy refractory to bisphosphonate therapy. We describe the use of denosumab for hypercalcemia of malignancy in a multiple myeloma only patient population that is not bisphosphonate refractory. The use of denosumab for these patients was part of normal clinical practice in adherence to institutional policies and guidelines.

Trends of skeletal related events in patients with breast cancer metastasized to bone.

1098 Background: Up to three-quarters of women with advanced breast cancer develop bone metastases, predisposing to Skeletal Related Events (SRE), which are associated with a significant health care burden, poor prognosis, loss of functional independence and a decrease in quality of life. We performed a retrospective analysis on predictors of SRE in this population. We also evaluated temporal trends of outcomes and resource utilization in those with SRE. Methods: Adult breast cancer patients with metastases to bone, admitted from January 2012 to September 2015 were identified from the Nationwide Inpatient Sample database. Based on previous studies, SRE was defined by using ICD-9 codes for pathologic fracture, spinal cord compression, necessity for radiation to bone or surgery to bone. Multivariable analysis of predictors of SRE in patients with breast cancer metastatic to bone, as well as mortality in the SRE group were performed. Temporal trends of resource utilization across the years were evaluated. Results: A total of 143,455 patients with breast cancer with metastases to bone were identified, of which 17.2% had SRE. Patients with SRE had a mean age of 66 years and were predominantly white (70.2%). After adjusting for confounders, African Americans and Hispanics were less likely than Whites to develop SRE. On multivariable analysis, only comorbidity burden (in the form of high Charlson comorbidity index) predicted inpatient mortality. Rates of SRE in breast cancer patients with bone metastases did not change over the years (17.2% to 17.1%). Inpatient mortality of patients with SRE remained stable (3.76% to 3.79%). There was a statistically significant increase in surgical intervention (43.4% to 47.7%, p&lt;0.01) and decrease in radiation to bone (25.7% to 19.7%, p&lt;0.001) over time. Length of hospital stay and total hospital charges, after adjusting for inflation, remained largely unchanged. Conclusions: Incidence of SRE, inpatient outcomes and health care costs remained stagnant in those with metastatic breast cancer between 2012 and 2015, despite the advent of novel bone-targeted agents. There has been an increased trend towards surgical intervention and less utilization of local radiation over time. [Table: see text]

Mid Regional Natriuretic Peptide for Predicting Prognosis of Hypertrophic Cardiomyopathy

Background: Hypertrophic cardiomyopathy (HCM) is a genetic disorder of cardiac myocytes that is characterized by cardiac hypertrophy, cellular disarray and interstitial fibrosis. Mutation of MYH7 and MYBPC3 encoding proteins β-myosin heavy chain and myosin binding protein C, respectively, are the two most common genes involved, together accounting for about 50% of cases. The present study was conducted to evaluate the prognostic value of MR-proANP in patients with HCM. Subjects and Methods: The present study was conducted at Narayana Medical College &amp; Hospital, Chintareddy Palem, Nellore, Andhra Pradesh from July 2016 to July 2017 on 46 patients of hypertrophic cardiomyopathy of both genders. Serum NT-proBNP was measured by a two-site electrochemiluminescence immunoassay on a Roche Diagnostics E170 analyser. Results: The mean systolic blood pressure was 124.8 mm Hg, diastolic blood pressure was 78 mm Hg, heart rate was 68 beats/minutes, NYHA 1(n=4), NYHA 2 (n=27), NYHA 3–4 (n=15) and atrial fibrillation was 12%. The mean MR-proANP was 106 pmol/L and NT-proBNP was 540 pg/mL at the start of the study. At the end of 12 months of follow up, 15 patients had a primary end point defined as heart failure hospitalisation (n=10), heart transplant (n=3) death(n=2). Both mean MR-proANP and NT-proBNP were strongly associated with the primary end points at the end of study period with values of 1010 pmol/L and 2545 pg/ml respectively. This showed a strong association with P &lt;0.05. Conclusion: Authors found that MR-proANP is a valuable biomarker for the prediction of heart failure related events in patients with HCM.

A Systematic Review and Meta-Analysis of Immune-Related Adverse Events of Anti-PD-1 Drugs in Randomized Controlled Trials.

Objective:We aimed to evaluate immune-related adverse events occurring in clinical trials of anti-programmed cell death 1 (PD-1) drugs, compared with control treatments, including chemotherapy, targeted drugs, or placebo. Further we compared the occurrence of immune -related events in patients treated with different anti-PD-1 drugs.Data Sources:Randomized controlled trial (RCT) data were sourced from PubMed, Embase, and the Cochrane Central Register of Controlled Trials combined with https://clinicaltrials.gov.Methods:Randomized controlled trial of anti-PD-1 drugs compared with control treatments published between January 1, 1970 and March 1,2019, were searched and data on trial patient characteristics, and adverse events extracted, reviewed, and subjected to meta-analysis.Results:Eighteen Randomized controlled trials were included in our study. The Randomized controlled trials compared nivolumab (n = 12), pembrolizumab (n = 6), with chemotherapy (n = 13), targeted drugs (n = 2), or placebo (n = 3). Compared with the control group, the risk of any immune-related adverse events in patients treated with anti-PD-1 drugs was increased (RR, 2.65; 95% confidence interval, 1.84–3.83; P < 0.00001). Of the immune-related adverse events, the risk rates of pneumonitis (risk ratio, 2.10; 95% CI, 0.85-5.18), colitis (2.96;1.62-5.38), hypophysitis(4.79;1.54-14.89), hypothyroidism(7.87;5.36-11.57), hyperthyroidism (7.03;4.35-11.34), rash (1.58;0.98-2.54), pruritus (2.28; 1.38-3.76), and hepatitis (9.31;2.18-39.85) were increased by anti-PD-1 drugs. Further, the risk of immune-related adverse events was similar for patients treated with pembrolizumab and nivolumab (P = 0.14).Conclusions:In addition to previously reported organ-specific immune-related adverse events, we found that the risk of hyperthyroidism was also increased, in anit-PD-1-treated patients, relative to control treatments. The risk of total immune-related adverse events, was similar for pembrolizumab and nivolumab.

Blood Pressure-Related Outcomes in a Diabetic Population.

See related article, pp 71–77 There has been significant controversy during the past decade about what is appropriate blood pressure control to optimally reduce cardiovascular disease– (CVD) and kidney disease–related events in patients with diabetes mellitus. The recent discussion on blood pressure targets in diabetes mellitus sets the stage for a thought-provoking contribution by Wu et al1 who reported that individuals with diabetes mellitus with persistently low pressures <120/80 mm Hg or pressures that drop below 120/80 mm Hg have an increase in CVD events and mortality over time. On the basis of data derived from larger clinical trials in those with diabetes mellitus, the seventh Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure advised a 130/80 mm Hg target.2 However, achieved systolic blood pressures in those trials were rarely below 130/80 mm Hg and limited to only a few studies.3,4 The Action of Control Cardiovascular Risk in Diabetes (ACCORD) trial was then designed to investigate whether targeting pressures in patients with diabetes down to 120/80 mm Hg would improve CVD outcomes to a greater extent than a goal of <140/90 mm Hg. At end of trial, the overall CVD results were null, but stroke was reduced in those with achieved pressures of <120/80 mm Hg.5 Another recent trial, the Systolic Blood Pressure Intervention Trial (SPRINT), was designed to investigate whether pressures <120/80 mm Hg would improve outcomes in patients with kidney disease compared with 140/90 mm Hg. The SPRINT investigators reported an improvement in fatal and nonfatal major CVD events in the intensive arm <120/80 mm Hg.6 Although …

The associated factors of skeletal related events in patients with non-small cell lung cancer.

e21640Background: Bone metastasis is frequently observed in advanced non-small cell lung cancer (NSCLC) accounting for 30-40%. Bone metastasis is sometimes symptomatic and causes severe pain or par...

Abstract P5-15-04: Zoledronic acid combined with adjuvant tamoxifen with or without ovarian function suppression in premenopausal early breast cancer patients

Abstract Background: Bisphosphonates can delay the onset and reduce the risk of skeletal related events in patients with bone metastatic breast cancer; it can prevent and controlcancer treatment-induced bone loss. Zoledronic acid (ZOL) plus adjuvant endocrine therapy significantly improved disease free survival. The aim of the study is to evaluate the benefits of ZOL combined with adjuvant therapy in premenopausal early breast cancer patients. Patients and methods: Patients were premenopausal females who had undergone primary surgery for stage I, II ER +ve and/or PR +ve breast cancer with &amp;lt; 10 positive lymph nodes. All 300 patients were scheduled for standard tamoxifen 20mg/day for five years plus goserelin 3.6 mg every 28 days and were randomized to ZOL 4mg every 6 months for 3 years (group A) and without ZOL (group B). The primary end points were toxicity and disease-free survival (DFS), while overall survival (OS) was the secondary end point. Results: Between April 2005 and March 2012, 300 patients were enrolled, the median follow up duration was 98.4 months (range 14-120 months), adding ZOL to endocrine therapy strongly suggests improved DFS versus endocrine therapy alone (90% versus 85% for an absolute increase of 5%). There were fewer disease recurrences in the ZOL group versus no ZOL group (12% vs. 16%) with the greatest reductions in the loco-regional recurrence (3% vs. 5%), distant metastasis (6% vs. 7%) and bone metastasis (3% vs. 5%). Conclusion: ZOL with adjuvant endocrine therapy were generally well tolerated with no reports of renal failure or osteonecrosis of the jaw. So, a twice yearly ZOL enhanced the efficacy of adjuvant endocrine treatment, and this benefit is maintained for long time. Citation Format: El-Ibrashi MM, El-Sadda WM, Abdel-Halim II, Elashri MS. Zoledronic acid combined with adjuvant tamoxifen with or without ovarian function suppression in premenopausal early breast cancer patients. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-15-04.

Skeletal related events in patients with bone metastasis arising from non-small cell lung cancer.

The skeleton is one of the most common sites of metastasis in patients with non-small cell lung cancer (NSCLC). Metastasis increases the risk of skeletal-related events (SREs). The purpose of this study is to evaluate the incidence of SREs and the factors associated with the development of SREs in patients with bone metastases (BM) arising from NSCLC. A cohort study was carried out involving 95 patients with BM associated with NSCLC who were enrolled between 2007 and 2011. Clinical and sociodemographic data were extracted from the physical and electronic records. The association between exposure variables and outcome (SREs) was assessed using crude odds ratio (OR). Survival analysis of patients with BM was conducted using the Kaplan-Meier method. A log-rank test was used to assess differences between the curves of those who did and did not experience SREs. Sixty-two out of 95 patients with BM (65.3 %) showed evidence of at least one SRE. Multiple analysis revealed that patients with a history of smoking (OR = 6.76; 95% CI = 1.3-33.0; p < 0.01), performance status ≥2 (OR = 3.38; 95% CI = 1.2-9.3; p < 0.01), and multiple BM (OR = 3.31; 95% CI = 1.1-9.9; p < 0.03) were at greater risk of SREs. Median survival time was 4.6 months (95% CI = 2.9-6.2) in patients who experienced SREs and 6.8 months (95% CI = 2.2-11.4) in patients who did not, a statistically significant difference (p = 0.03). Patients with NSCLC are more likely to experience SREs if they have poor performance status, a history of smoking or multiple BM. Global survival was shorter in patients who suffer SREs.

Carcinoma da próstata metastático resistente à castração - novas abordagens terapêuticas

Prostate cancer is the most common noncutaneous malignancy in males and the second cause of cancer related mortality amongst men in the Western World. It is estimated that up to 40% of individuals diagnosed with this tumor will develop metastatic disease. Although there is a favorable initial response to medical or surgical castration, progression to a castration-resistance state is universal. Over the last decade new therapeutic targets for CRPC were identified, which raised the development of multiple new drugs. In 2010, the “Food and Drug Administration “ (FDA) approved the use of sipuleucel-T and cabazitaxel, in 2011 and 2012 abiraterone and enzalutamide respectively, were introduced for the treatment of metastatic CRPC. Denosumab and alpharadin were also approved for the prevention of skeleton related events in patients with bone metastasis, providing an alternative to zoledronic acid. With this article, the authors intend to conduct a systematic review of the latest clinical evidence and new approaches to CRPC© 2014 Associação Portuguesa de Urologia. Published by Elsevier España, S.L.U. All rights reserved.