Factors that determine survival among patients with multiple myeloma (MM) treated with zoledronic acid (ZOL)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e19519-e19519
Author(s):  
O. Yellin ◽  
J. Crowley ◽  
R. A. Swift ◽  
A. Makary ◽  
D. S. Gravenor ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Factors ◽  
Treatment Options ◽  
Elevated Serum ◽  
Osteonecrosis Of The Jaw ◽  
Morbidity Rate ◽  
Diabetic Patients ◽  
Increased Risk ◽  
Skeletal Complications ◽  
New Treatment

e19519 Background: Although the overall survival of MM patients has improved with new treatment options, few studies have evaluated prognostic factors since these new therapies have become available. Monthly ZOL has been incorporated into many of these regimens to reduce skeletal complications. Side effects from ZOL have been reported but their frequency and outcomes have not been well-defined. This retrospective study aimed to identify key baseline and on-treatment prognostic factors among MM patients treated with ZOL. Methods: Three hundred patient charts were consecutively reviewed. Data was collected from the date of MM diagnosis to the date of chart review. Patient chart inclusion criteria required a diagnosis of MM and having received at least one dose of ZOL. Results: The median survival of among patients in this study was 131 months. Significant early risk factors for overall survival included skeletal-related events (SRE), increased serum creatinine, elevated serum calcium, and ISS Stage II or III at diagnosis. Fourteen patients (4.7%) developed osteonecrosis of the jaw (ONJ) after 9–96 months of ZOL treatment. Notably, there was a trend toward an increased risk of ONJ among diabetic patients. Thirteen patients with ONJ remain alive and currently are in remission or with stable disease. One patient with ONJ died while in remission from a myocardial infarction. Among the patients with a follow up of 4–49 months from the diagnosis of ONJ, 2 showed some worsening of this complication, 5 remained stable, while 7 improved or resolved. Patients with ONJ showed an improved overall survival using both landmark and time-dependent analysis. In addition, the overall skeletal morbidity rate (SMR; SREs/year) was 0.16. Notably, patients who developed ONJ had a lower SMR than among patients who did not develop ONJ. Conclusions: These results suggest that skeletal complications are an important prognostic factor for MM. Although ONJ occurs in MM patients, most patients show improvement with proper management and this complication appears to be associated with a reduced risk of SREs and improved overall survival. [Table: see text]

Factors That Determine Overall Survival among Patients (Pts) with Multiple Myeloma (MM) Treated with Zoledronic Acid (ZOL): Lack of Skeletal-Related Events (SREs) and Occurrence of Osteonecrosis of the Jaw (ONJ) Predict Improved Survival.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4842-4842
Author(s):  
James R. Berenson ◽  
Ori Yellin ◽  
John Crowley ◽  
Herbert Duvivier ◽  
Youram Nassir ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Factors ◽  
Serum Creatinine ◽  
Serum Calcium ◽  
Treatment Options ◽  
Elevated Serum ◽  
Time Dependent ◽  
Stage Ii ◽  
The Past ◽  
New Treatment

Abstract New treatment options have greatly improved the overall survival for MM pts. Although many baseline prognostic factors have been identified among pts with MM in the past, few studies have evaluated prognostic factors during the past five years when these new treatment options became available. Included in the newer regimens for myeloma pts is the use of monthly infusions of ZOL to reduce skeletal complications for MM pts. During this time of changes in the therapy for MM pts, complications associated with administration of bisphosphonates have been reported among MM pts. The outcome for patients with these complications has not been well-defined. The goal of this study was to identify baseline and on-treatment prognostic factors for determining overall survival of MM pts treated with ZOL. The inclusion criteria for this study included a diagnosis of MM and having received at least one dose of ZOL in our clinic. One hundred consecutive pts were analyzed in this retrospective study. The median survival of this group was 117 months. Risk factors for an earlier death included occurrence of a SRE (hazard ratio [HR] = 3.06), increased serum creatinine (HR = 3.35), elevated serum calcium (HR = 2.60), and ISS Stage II or III at diagnosis (HR = 2.04). Notably, diabetes was found to be a significant risk factor for SREs but not overall survival (P = 0.022). Ten pts developed ONJ, of whom nine are alive and one died in remission (non-MM-related). The 2-year incidence of ONJ was approximately 5%. There was a trend toward increased risk of ONJ for diabetes, smoking, and alcohol use. When evaluating the course of ONJ, only one pt showed progression, while six improved or resolved, and three remained stable. All but one pt with ONJ remain on monthly ZOL therapy. In regards to the disease status of the nine pts surviving with ONJ, five are in complete remission, two with ongoing partial responses, and two have stable disease. The skeletal morbidity rate (SMR) was only 0.16 SRE/year among all 100 pts analyzed. Notably, pts with ONJ had a lower SMR (0.07 SRE/year) than the 90 pts treated with ZOL who did not develop ONJ (0.18 SRE/year). Importantly, overall survival was superior among pts with ONJ versus pts without ONJ in this study when analyzed both by a landmark analysis and in a time-dependent fashion. Thus, development of new SREs, elevated serum creatinine, increased serum calcium and ISS Stage II or III at diagnosis predicted for an earlier death. With active monitoring for ONJ and early input from dental experts, ONJ has been mild to moderate in severity, had minimal impact on overall quality of life, and improved or healed in the majority of pts. In this study, absence of SREs (time-dependent) and occurrence of ONJ were associated with an improved overall survival (P ≤ .01 for each). These results suggest that with proper management, ONJ is a manageable, infrequent complication of ZOL that may be associated with a reduced SRE risk and improved overall survival. This study also suggests the avoidance of SREs is associated with an increased life expectancy; and, thus, reduction in these events through ongoing bisphosphonate therapy is important in the overall management of MM pts.

Proteomic Analysis of the Vitreous Body in Proliferative and Non-Proliferative Diabetic Retinopathy

2020 ◽  
Vol 17 ◽  
Author(s):  
Van-An Duong ◽  
Jeeyun Ahn ◽  
Na-Young Han ◽  
Jong-Moon Park ◽  
Jeong-Hun Mok ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Proliferative Diabetic Retinopathy ◽  
Microvascular Complications ◽  
Treatment Options ◽  
Vitreous Body ◽  
Control Group ◽  
Diabetic Patients ◽  
Protein Protein Interaction ◽  
Alpha Beta ◽  
New Treatment

Background: Diabetic Retinopathy (DR), one of the major microvascular complications commonly occurring in diabetic patients, can be classified into Proliferative Diabetic Retinopathy (PDR) and Non-Proliferative Diabetic Retinopathy (NPDR). Currently available therapies are only targeted for later stages of the disease in which some pathologic changes may be irreversible. Thus, there is a need to develop new treatment options for earlier stages of DR through revealing pathological mechanisms of PDR and NPDR. Objective: The purpose of this study was to characterize proteomes of diabetic through quantitative analysis of PDR and NPDR. Methods: Vitreous body was collected from three groups: control (non-diabetes mellitus), NPDR, and PDR. Vitreous proteins were digested to peptide mixtures and analyzed using LC-MS/MS. MaxQuant was used to search against the database and statistical analyses were performed using Perseus. Gene ontology analysis, related-disease identification, and protein-protein interaction were performed using the differential expressed proteins. Results: Twenty proteins were identified as critical in PDR and NPDR. The NPDR group showed different expressions of kininogen-1, serotransferrin, ribonuclease pancreatic, osteopontin, keratin type II cytoskeletal 2 epidermal, and transthyretin. Also, prothrombin, signal transducer and activator of transcription 4, hemoglobin subunit alpha, beta, and delta were particularly up-regulated proteins for PDR group. The up-regulated proteins related to complement and coagulation cascades. Statherin was down-regulated in PDR and NPDR compared with the control group. Transthyretin was the unique protein that increased its abundance in NPDR compared with the PDR and control group. Conclusion: This study confirmed the different expressions of some proteins in PDR and NPDR. Additionally, we revealed uniquely expressed proteins of PDR and NPDR, which would be differential biomarkers: prothrombin, alpha-2-HS-glycoprotein, hemoglobin subunit alpha, beta, and transthyretin.

Demographic, Clinical, and Prognostic Factors of Ovarian Clear Cell Adenocarcinomas According to Endometriosis Status

2017 ◽  
Vol 27 (9) ◽  
pp. 1804-1812 ◽  
Author(s):  
Tine H. Schnack ◽  
Estrid Høgdall ◽  
Lotte Nedergaard Thomsen ◽  
Claus Høgdall
Keyword(s):  
Overall Survival ◽  
Prognostic Factors ◽  
Cox Regression ◽  
Clear Cell ◽  
Statistical Tests ◽  
Gynecological Cancer ◽  
Population Based ◽  
Clear Cell Adenocarcinoma ◽  
Ovarian Endometriosis ◽  
Increased Risk

ObjectivesWomen with endometriosis carry an increased risk for ovarian clear cell adenocarcinomas (CCCs). Clear cell adenocarcinoma may develop from endometriosis lesions. Few studies have compared clinical and prognostic factors and overall survival in patients diagnosed as having CCC according to endometriosis status.MethodsPopulation-based prospectively collected data on CCC with coexisting pelvic (including ovarian; n = 80) and ovarian (n = 46) endometriosis or without endometriosis (n = 95) were obtained through the Danish Gynecological Cancer Database. χ2 Test, independent-samples t test, logistic regression, Kaplan-Meier test, and Cox regression were used. Statistical tests were 2 sided. P values less than 0.05 were considered statistically significant.ResultsPatients with CCC and pelvic or ovarian endometriosis were significantly younger than CCC patients without endometriosis, and a higher proportion of them were nulliparous (28% and 31% vs 17% (P = 0.07 and P = 0.09). Accordingly, a significantly higher proportion of women without endometriosis had given birth to more than 1 child. Interestingly, a significantly higher proportion of patients with ovarian endometriosis had pure CCCs (97.8% vs 82.1%; P = 0.001) as compared with patients without endometriosis. Overall survival was poorer among CCC patients with concomitant ovarian endometriosis (hazard ratio, 2.56 [95% confidence interval, 1.29–5.02], in the multivariate analysis.ConclusionsAge at CCC diagnosis and parity as well as histology differ between CCC patients with and without concomitant endometriosis. Furthermore, CCC patients with concomitant ovarian endometriosis have a poorer prognosis compared with endometriosis-negative CCC patients. These differences warrant further research to determine whether CCCs with and without concomitant endometriosis develop through distinct pathogenic pathways.

scholarly journals Prognostic factors for pulmonary metastasectomy in malignant melanoma: size matters

2019 ◽  
Vol 56 (6) ◽  
pp. 1104-1109 ◽  
Author(s):  
Jan Viehof ◽  
Elisabeth Livingstone ◽  
Elena Loscha ◽  
Paul Stockhammer ◽  
Agnes Bankfalvi ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Factors ◽  
Survival Rate ◽  
Malignant Melanoma ◽  
Treatment Options ◽  
Pulmonary Metastasectomy ◽  
Long Term Outcome ◽  
Female Patients ◽  
Novel Treatment ◽  
The Impact

AbstractOBJECTIVESPulmonary metastasectomy for malignant melanoma requires an individualized therapeutic decision. Due to recently developed novel treatment options, the prognosis of patients with melanoma has improved significantly. Validated prognostic factors that identify patients who are most likely to benefit from metastasectomy are urgently needed.METHODSWe retrospectively reviewed all consecutive patients with melanoma undergoing complete pulmonary metastasectomy between January 2010 and December 2016. The impact of age, sex, extrapulmonary metastases, preoperative systemic therapy, number of metastases, laterality and largest diameter of metastasis on survival after metastasectomy was analysed.RESULTSA total of 29 male and 32 female patients were included in the study. The median follow-up time was 25.6 months. The mean number of resected metastases was 1.7 ± 1.1 (range 1–5). Ten patients had repetitive pulmonary metastasectomies. The median survival time was 31.3 months with a 2-year survival rate of 54%. Bilateral metastases or multiple nodules were not associated with a significantly decreased overall survival rate after metastasectomy. Shorter overall survival times were observed in male patients [hazard ratio (HR) 2.9, 95% confidence interval (CI) 1.42–5.92; P = 0.0035] and in patients with nodules larger than 2 cm (HR 3.18, 95% CI 1.45–6.98; P = 0.004). In multivariable analysis, both gender and tumour size remained significant independent prognostic factors.CONCLUSIONSExcellent overall survival rates after pulmonary metastasectomy for melanoma metastases were observed in patients with a metastatic diameter less than 2 cm and in female patients. In view of improved long-term outcome due to novel treatment options, the selection of patients for pulmonary metastasectomy based on prognostic factors will become increasingly important.

Expression of Phosphorylated Signal Transducer and Activator of Transcription 5 (pSTAT5) Is Associated with An Increased Risk of Death In Acute Myeloid Leukemia.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1675-1675
Author(s):  
Anna Brady ◽  
Sarah Gibson ◽  
Lisa Rybicki ◽  
Eric Hsi ◽  
Edward Copelan ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Prognostic Factors ◽  
Myeloid Leukemia ◽  
Signal Transducer ◽  
Newly Diagnosed ◽  
Risk Of Death ◽  
Increased Risk ◽  
History Of ◽  
Acute Myeloid

Abstract Abstract 1675 Background: Acute myeloid leukemia (AML) is characterized by rapid growth, resistance to therapy, and poor overall survival. Clinical and biologic prognostic markers can help define pathogenesis, guide treatment, and identify novel therapies. Phosphorylated signal transducer and activator of transcription 5 (pSTAT5) is one such potential marker. The transcription factor STAT5 regulates many aspects of cell growth, survival, and differentiation. Constitutive activation of STAT5 (by phosphorylation) has been identified in a number of malignancies, including AML. We investigated whether the level of pSTAT5 expression correlates with complete remission (CR) rates, progression-free survival (PFS), and overall survival (OS) in patients (pts) with newly diagnosed AML. Methods: From 1999 to 2005, all adult pts with newly diagnosed AML (WHO criteria) receiving induction chemotherapy and with an available diagnostic bone marrow biopsy performed at our institution were evaluated. B5-fixed bone marrow core biopsies were reviewed for areas with the highest concentration of blasts. A tissue microarray was constructed using 1 mm cores. The cores were arrayed in duplicate in the majority of samples. Immunohistochemistry was performed for pSTAT5 with anti-pSTAT5 a/b Y695/99 mouse monoclonal antibody (AX1; Advantex Bioreagents) using automated stainers and heat-induced epitope retrieval. In each case, five hundred blasts were counted. The percentage of cells staining positive for pSTAT5 expression was determined by a pathologist blinded to clinical results. Standard metaphase karyotypes were classified into cytogenetic (CG) risk groups by CALGB criteria. Cox proportional hazards analysis was used to identify univariate and multivariate prognostic factors for CR, PFS, and OS, including age at diagnosis, history of an antecedent hematologic disorder (AHD), WBC at diagnosis, pSTAT5 expression, and CG risk group. Results: Adequate tissue and clinical data were available in 112 pts. The median age was 57 years, and median WBC at diagnosis 12.0 K/ μL. Twenty six percent of pts had favorable CG, 41% intermediate risk, 27% high risk, and 6% other (unknown or could not be classified). Nineteen percent of pts had an AHD. pSTAT5 expression was absent in 58% of pts. The remainder of the pts had: 1–5% pSTAT5 (25% of pts), 10% pSTAT5 (11% of pts), 20% pSTAT5 (4% of pts), 30% pSTAT5 (1% of pts), and 50% pSTAT5 (2% of pts). Seventy percent of all pts achieved a CR following induction chemotherapy. Sixty-four percent of pts received post-remission chemotherapy, 3.6% an autologous transplant, and 13.6% an allogeneic transplant in first CR. Median PFS and OS were 9.6 months and 16.0 months, respectively. On univariate analysis, age, history of AHD, WBC at diagnosis, CG risk, and any pSTAT5 expression were prognostic factors for PFS and OS. In multivariable analyses controlling for the above prognostic factors, pSTAT5 expression > 0 was also significantly associated with an increased risk of death (HR 1.96, 95% CI 1.19–3.23, p=0.008), progression or death (HR 1.64, 95% CI 1.01–2.66, p=0.046), and relapse after achieving CR (HR 2.31, 95% CI 1.16–4.63, p=0.018). pSTAT5 expression was not a predictor of achievement of CR. Conclusions: pSTAT5 expression in newly diagnosed adults with AML is associated with a decreased PFS, decreased OS, and increased risk of relapse. Validation of its prognostic value requires additional study. Agents targeting this signaling pathway might improve the outcome of pts with AML. Disclosures: No relevant conflicts of interest to declare.

scholarly journals A study of the influence of lipid profile in diabetic patients on the incidence of cerebrovascular events

2019 ◽  
Vol 6 (3) ◽  
pp. 816
Author(s):  
Taha Mahboob Ali Khalid ◽  
Rahul Gandhi G.
Keyword(s):  
Lipid Profile ◽  
Plasma Concentrations ◽  
Elevated Serum ◽  
Rapid Onset ◽  
Diabetic Patients ◽  
Mean Values ◽  
Cerebrovascular Events ◽  
Serum Lipid Concentration ◽  
Increased Risk ◽  
The Difference

Background: The relationship between elevated serum lipids and atherosclerosis is well established. Recent studies have demonstrated not only that the serum lipid concentration but also the distribution of TG and cholesterol within major lipoprotein classes are of importance for the development of atherosclerosis. Elevated plasma concentrations of LDL and decreased HDL are associated with increased risk of atherosclerosis. To study the influence of lipid profile in diabetic patients on the incidence of cerebrovascular events.Methods: The study was based on 60 patients meeting the inclusion criteria from those who were admitted at Shadan Institute of Medical Sciences, Hyderabad, India from Feb 2013-May 2014. Detailed history was taken and thorough physical examination done pertaining to the involved condition. Patients who were conscious, slow progression of neurological deficit, rapid onset of lateralizing signs with variable blood pressure were considered to be suffering from infarction.Results: The mean values of lipid profile were significantly different among the gender. There were more females with medium and high TC values as compared to females and this difference was found to be significant. Though the number of females with high HDL values was more than males, the difference was not found to be significant. The number of females with high LDL values was far more than males and this difference was found to be significant. Though the number of females was more with high TG values, the difference was not found to be significant.Conclusions: In conclusion, our study gives evidence that poor glycemic control is a strong risk factor for stroke in patients with NIDDM.

Revascularization Outcomes in Patients With Acute Limb Ischemia and Active Neoplastic Disease

2020 ◽  
pp. 152660282095428
Author(s):  
Angeliki Argyriou ◽  
Alexandros Kafetzakis ◽  
Athanasios Saratzis ◽  
Bella Huasen ◽  
Raphaël Coscas ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cox Regression ◽  
Treatment Options ◽  
Limb Ischemia ◽  
Free Time ◽  
Neoplastic Disease ◽  
Acute Limb Ischemia ◽  
Cox Regression Analysis ◽  
Increased Risk ◽  
Common Diagnosis

Purpose To report the outcomes of surgical (ST), endovascular (ET), and hybrid (HT) treatment in cancer patients with acute limb ischemia (ALI). Materials and Methods A multicenter retrospective registry collected 139 patients (mean age 72.3±12.4 years; 73 men) with ALI and active malignancy treated by ET (41, 29%), ST (70, 51%), or HT (28, 20%) in 7 European centers between July 2007 and February 2019. In 22 cases (16%) ALI was the first manifestation of the malignancy. Lung cancer was the most common diagnosis (38, 27%). The primary composite outcome was amputation-free survival (AFS). Overall survival, amputation-free time (AFT), and reintervention-free time (RFT) were also assessed. Cox regression analysis was applied to identify independent risk factors for the primary and secondary outcomes. Results are presented as the hazard ratio (HR) and 95% confidence intervals (CIs). Results ET was associated with improved 12-month AFS compared with both ST (HR 2.27, 95% CI 1.20 to 4.28, p=0.002) and HT (HR 2.14, 95% CI 1.09 to 4.18, p=0.008). ST (HR 2.50, 95% CI 1.19 to 5.53, p=0.003) and HT (HR 3.10, 95% CI 1.45 to 6.65, p<0.001) were related to an increased risk for mortality compared with ET. At 12 months, the AFT was similar between the 3 groups (ET vs ST: HR 1.52, 95% CI 0.51 to 4.53, p=0.45 and ET vs HT: HR 1.21, 95% CI 0.36 to 4.11, p=0.73). The 12-month RFT also did not differ significantly between the 3 treatment options (ET vs ST: HR 1.10, 95% CI 0.49 to 2.46, p=0.79 and ET vs HT: HR 0.51, 95% CI 0.22 to 1.17, p=0.19). ST and/or HT increased the risk for the major amputation and/or death (HR 1.76, 95% CI 1.05 to 2.05, p=0.03), while Rutherford class I ischemia (HR 0.12, 95% CI 0.02 to 0.90, p=0.04) and previous vascular interventions on the index limb (HR 0.55, 95% CI 0.32 to 0.97, p=0.04) showed a protective effect. Conclusion In patients with ALI and active malignant disease, ET was associated with increased AFS and overall survival compared with both ST and HT, while the limb salvage and reintervention rates were comparable among the 3 groups.

A population-based analysis of prognostic factors in patients with advanced hepatocellular carcinoma treated with sorafenib.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 163-163
Author(s):  
Alan D. Smith ◽  
Winson Y. Cheung
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Prognostic Factors ◽  
Elevated Serum ◽  
Advanced Hepatocellular Carcinoma ◽  
Clinical Factors ◽  
Conventional Chemotherapy ◽  
Sorafenib Treatment ◽  
Advanced Hcc ◽  
Staging Systems

163 Background: Available clinical prognostic scoring systems for advanced hepatocellular carcinoma (HCC) were developed in the era of conventional chemotherapy. In 2008, the molecularly targeted agent sorafenib became the new standard of care for advanced HCC due to its survival benefit. The utility of these prognostic models in the setting of sorafenib is unclear. Our aims were to assess for new prognostic factors in patients treated with sorafenib and compare these with known prognostic systems. Methods: All patients diagnosed with advanced HCC from 2008 to 2010 in British Columbia, Canada and treated with sorafenib at any 1 of 5 regional cancer centers were eligible. Based on the established Okuda, CLIP, Barcelona, and French staging systems, we collected baseline demographic and disease characteristics of patients prior to receipt of sorafenib. Multivariate logistic regression models were constructed to examine for associations between these clinical factors and overall survival. Results: Of 183 patients identified, 152 were evaluable: median age was 63 years, 78% were men, average number of sorafenib treatment was 5.3 cycles, and median overall survival was 9.6 months. The prevalence of hepatitis B, hepatitis C, and alcohol-related liver disease were 32%, 15%, and 11%, respectively. Univariate analyses showed that poor performance status, presence of clinical ascites, as well as elevated serum AST, GGT, ALP, bilirubin and platelet levels were each associated with worse overall survival (all p<0.05). In multivariate analyses, however, none of these clinical factors continued to be independently predictive of outcome (all p>0.05). Conclusions: Traditional clinical prognostic factors developed in the era of conventional chemotherapy do not appear to have the same prognostic utility in this contemporary Western cohort of advanced HCC patients treated with sorafenib. This observation underscores the need to identify molecular biomarkers that provide better prognostic information.

Effect of metformin on recurrence-free survival and overall survival in diabetic patients affected by advanced ovarian cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 5522-5522 ◽  
Author(s):  
Cecilia Simonelli ◽  
Monica Bertolotti ◽  
Paul Sabbatini ◽  
Jonathan S. Berek ◽  
Jacobus Pfisterer ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Prognostic Factors ◽  
Proportional Hazards Model ◽  
Advanced Ovarian Cancer ◽  
Cox Proportional Hazards Model ◽  
Diabetic Patients ◽  
Recurrence Free Survival ◽  
Double Blind ◽  
Free Survival

5522^ Background: Metformin, has recently shown some anti-cancer activities in ovarian cancer, both in vitro and in vivo. Methods: Analysis of Recurrence Free Survival (RFS) and Overall Survival (OS) was performed in patients (pts) with diabetes (D) treated with metformin (DMet+) or not (DMet-) enrolled in the MIMOSA trial, a randomized double-blind placebo-controlled international trial of Abagovomab maintenance therapy in 888 pts with advanced ovarian cancer. In the MIMOSA trial, no differences in the RFS and OS were observed between Abagovomab (n = 593) and Placebo arm (n = 295); hence, the present RFS and OS analysis (DMet+ vs DMet-) was run regardless of treatment allocation. A Cox proportional hazards model was used for adjusting the analysis for the predefined prognostic factors: Figo stage (III, IV), tumor size after debulking (residual tumor <1 cm, >1cm); CA125 serum level after 3th cycle (<35U/ml, >35U/ml). In addition, comparison of RFS and OS was done between DMet+and the overall MIMOSA population not exposed to metformin (ALLMet-), and between the overall diabetic pts (ALLD+) and non-diabetic pts (ALLD-). Results: In the ALL population (n = 888), 42 pts were affected by diabetes (ALLD+) divided to DMet+ (n = 27) and DMet- (n = 15), without difference in the prognostic factors distribution. When analysis was done in ALLD+, RFS median time was not reached in the DMet+ group whereas it was 328 days [CI: 30-660] in DMet- group with HR favoring DMet+=0.419 [CI:0.175-1.002]; p = 0.05. Median OS time was also not reached in the DMet+ group whereas it was 786 days [CI:262-NE] in DMet- group with HR=0.295 [CI:0.109-0.803]; p = 0.02. Interestingly HR for RFS time was still in favour of DMet+ group when compared to the ALLMet- (n=861) with HR=0.575 (CI=0.324-1.022); p = 0.06. When ALLD+ were compared with ALLD-(n = 846), no significant differences was detected in RFS and OS time. Conclusions: The present results are the first prospectively analyzed data demonstrating a favourable impact of metformin treatment on RFS and OS in pts affected by advanced ovarian cancer. Clinical trial information: NCT00418574.

scholarly journals The Potential Role of Osteopontin and Furin in Worsening Disease Outcomes in COVID-19 Patients with Pre-Existing Diabetes

Cells ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 2528
Author(s):  
Yvonne Adu-Agyeiwaah ◽  
Maria B. Grant ◽  
Alexander G. Obukhov
Keyword(s):  
Elevated Serum ◽  
Premature Mortality ◽  
Proteolytic Processing ◽  
Diabetic Patients ◽  
Metabolic Dysfunction ◽  
The Novel ◽  
Disease Outcomes ◽  
Increased Risk ◽  
Patients With Diabetes

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the ongoing coronavirus disease 2019 (COVID-19) pandemic, with more than 50 million cases reported globally. Findings have consistently identified an increased severity of SARS-CoV-2 infection in individuals with diabetes. Osteopontin, a cytokine-like matrix-associated phosphoglycoprotein, is elevated in diabetes and drives the expression of furin, a proprotein convertase implicated in the proteolytic processing and activation of several precursors, including chemokines, growth factors, hormones, adhesion molecules, and receptors. Elevated serum furin is a signature of diabetes mellitus progression and is associated with a dysmetabolic phenotype and increased risk of diabetes-linked premature mortality. Additionally, furin plays an important role in enhancing the infectivity of SARS-CoV-2 by promoting its entry and replication in the host cell. Here, we hypothesize that diabetes-induced osteopontin and furin protein upregulation results in worse outcomes in diabetic patients with SARS-CoV-2 infection owing to the roles of these protein in promoting viral infection and increasing metabolic dysfunction. Thus, targeting the osteopontin-furin axis may be a plausible strategy for reducing mortality in SARS-CoV-2 patients with diabetes.

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