Full Dose of Lenalidomide for 12 Months Followed by a Lower Maintenance Dose Improves Progression-Free Survival in Patients with Relapsed/Refractory Multiple Myeloma.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2874-2874 ◽  
Author(s):  
Meletios A Dimopoulos ◽  
Mohamad Hussein ◽  
Arlene S. Swern ◽  
Donna Weber
Keyword(s):  
Dose Reduction ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Duration Of Treatment ◽  
Cox Regression Analysis ◽  
Full Dose ◽  
Group A ◽  
Group B ◽  
Dose Reductions

Abstract Abstract 2874 Poster Board II-850 Background: Lenalidomide (len) is an oral immunomodulatory agent which is active in patients (pts) with multiple myeloma (MM). Two pivotal phase III studies in pts with relapsed/refractory MM (MM-009 and MM-010) demonstrated significant improvements in time to progression (TTP) and overall survival (OS) in those receiving len + dexamethasone (dex) compared to pts receiving placebo + dexamethasone. The aim of this analysis is to evaluate the effect of lenalidomide dose adjustments on patient outcomes from the MM-009/010 studies in order to determine an optimal long-term treatment strategy. Methods: Data up to the cut-off date of July 2008 were included in this analysis. All pts began lenalidomide at 25 mg daily for 21 days of each 28-day cycle. As previously described a protocol sanctioned dose reduction was only for an adverse event (AE). All pts received the same dose of dex. The impact of lenalidomide dose reduction, either before or after 12 months of therapy vs no dose reduction, on response and progression-free survival (PFS) was evaluated by performing a landmark analysis including only pts who had not progressed and were still on lenalidomide at 12 months . Pts were categorized based on their lenalidomide dose as follows: Group A (dose reduced from 25 mg daily therapy prior to 12 months. Group B (dose reduced from 25 mg daily therapy after 12 months), and Group C (no dose reduction during the study period). To control for possible biases in the comparison of these groups, only pts who were progression free and still receiving lenalidomide treatment at 12 months were included in the analysis. To determine if underlying factors, in addition to the reduction in dose, influenced PFS in these patient cohorts, baseline patient characteristics and laboratory values at baseline and 12 months were assessed with Cox regression analysis using PFS. Each covariate was evaluated by itself and all covariates with a p-value <0.25 were included in a multivariate model and all possible regression models were analyzed to select the best subset of covariates Results: Of the 116 pts who were still receiving lenalidomide and that had not progressed after 12 months, 39 (34%) had a dose reduction prior to 12 months (Group A), 25 (22%) had a dose reduction after 12 months (Group B), and 52 (45%) had no dose reduction at any time (Group C). Pts who were treated with lenalidomide 25 mg daily for at least 12 months and subsequently had dose reductions (Group B) demonstrated significantly longer PFS (median PFS not yet reached at median follow-up of 48 months) compared to pts who experienced a dose reduction prior to completing 12 months of therapy at 25 mg daily (Group A, median PFS 28.0 months, p= 0.007) or pts who never had a dose reduction (Group C, median PFS 36.8 months, p=0.039). Similarly, pts in Group B had longer median duration of treatment (44.4 months) compared to Group A (23.5 months) or Group C (29.7 months). Among pts who experienced a dose reduction, there was a similar rate of dose reductions due to AEs in each group (Group A – 92.3%, Group B – 88.0%). However, among all pts a higher rate of neutropenia (Group A – 71.8%, Group B – 76.0% Group C – 44.2%) and thrombocytopenia (Group A – 38.5%, Group B – 24.0%, Group C – 13.5%) was observed in pts with a dose reduction before or after 12 months. In the Cox regression analysis using PFS as an endpoint, pts reducing their dose after 12 months (Group B), had a 53% lower risk of progression or death compared to Groups A and C. A significantly higher proportion of pts in Group B exhibited a poorer ECOG performance status (PS) (79.2%, PS ≥ 1) vs 48.8%, PS ≥ 1) for Group A and C p < 0.01) Despite this difference, the significant improvement in PFS in Group B pts compared to other patient groups was maintained. Conclusions: This analysis suggests that pts responding and maintained on a full dose of lenalidomide (25 mg daily for 21 days of a 28-day cycle) for the first 12 months of therapy benefit from subsequent dose reductions. This was demonstrated by a statistically significant improvement in PFS in pts receiving dose reduction only after completing 12 months of full dose therapy. These data support the hypothesis that a lower maintenance dose of lenalidomide after 12 months of full dose therapy improves long-term patient tolerability and extends the duration of treatment, thereby improving long-term outcomes. Further studies to define the role of immunologic modulation and maintenance therapy are in progress. Disclosures: Dimopoulos: Celgene Corporation: Honoraria. Hussein:Celgene Corporation: Employment. Swern:Celgene: Employment. Weber:Celgene Corporation: Honoraria, Research Funding.

scholarly journals Extensive Dissection at No. 12 Station During D2 Lymphadenectomy Improves Survival for Advanced Lower-Third Gastric Cancer: A Retrospective Study From a Single Center in Southern China

2022 ◽  
Vol 11 ◽  
Author(s):  
Weigang Dai ◽  
Er-Tao Zhai ◽  
Jianhui Chen ◽  
Zhihui Chen ◽  
Risheng Zhao ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cox Regression ◽  
Southern China ◽  
Progression Free Survival ◽  
Control Group ◽  
D2 Lymphadenectomy ◽  
Term Survival ◽  
Cox Regression Analysis ◽  
Group A

BackgroundD2 lymphadenectomy including No. 12a dissection has been accepted as a standard surgical management of advanced lower-third gastric cancer (GC). The necessity of extensive No. 12 nodes (No. 12a, 12b, and 12p) dissection remains controversial. This study aims to explore its impact on long-term survival for resectable GC.MethodsFrom 2009 to 2016, 353 advanced lower-third GC patients undergoing at least D2 lymphadenectomy during a radical surgery were included, with 179 patients receiving No. 12a, 12b, and 12p dissection as study group. A total of 174 patients with No. 12a dissection were employed as control group. Surgical and long-term outcomes including 90-day complications incidence, therapeutic value index (TVI), 3-year progression-free survival (PFS), and 5-year overall survival (OS) were compared between both groups.ResultsNo. 12 lymph node metastasis was observed in 20 (5.7%) patients, with 10 cases in each group (5.6% vs. 5.7%, p = 0.948). The metastatic rates at No. 12a, 12b, and 12p were 5.7%, 2.2%, and 1.7%, respectively. The incidence of 90-day complications was identical between both groups. Extensive No. 12 dissection was associated with increased TVI at No. 12 station (3.9 vs. 0.6), prolonged 3-year PFS rate (67.0% vs. 55.9%, p = 0.045) and 5-year OS rate (66.2% vs. 54.0%, p = 0.027). The further Cox-regression analysis showed that the 12abp dissection was an independent prognostic factor of improved survival (p = 0.026).ConclusionAdding No. 12b and 12p lymph nodes to D2 lymphadenectomy might be effective in surgical treatment of advanced lower-third GC and improve oncological outcomes compared with No. 12a-based D2 lymphadenectomy.

P2852Risk factors for death and survival after TLE in the groups of eighty- and ninety-year-olds

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
W Jachec ◽  
A Polewczyk ◽  
L Segreti ◽  
M G Bongiorni ◽  
A Kutarski
Keyword(s):  
Risk Factors ◽  
Old Age ◽  
Cox Regression ◽  
Nyha Class ◽  
Lead Extraction ◽  
Cox Regression Analysis ◽  
Group A ◽  
Group B

Abstract Background Despite the fact that the transvenous lead extraction (TLE) is the method of choice of treatment for pacing complications, these procedures are not often performed in the elderly. The prognosis after TLE in these groups of patients is uncertain. Aim Evaluation of risk factors for death of patients who underwent TLE over the age 80 and 90 years. Methods 3368 patients with complete follow-up data (mean age at the time of procedure; 65.38±15.64 years old, 1198 female) who underwent TLE procedures in two high volume experienced European centers. Risk factors for death in patients divided in to three groups depending on the age: below the age of 80 (group A, n=2854) and in groups of eighty-years-old (group B, n=484) and ninety-years old (group C, n=30) were determined using the Cox multivariable model. The survival of eighty-year-olds and ninety-year-olds was worse compared to younger patients and they did not differ between themselves (Figure 1). Results 815 deaths occurred during 3.87±2.76 years of follow-up; 611 (21.4%) in group A, 192 (39.7%) in group B (p<0,001) and 12 (40%) in group C (p<0.001) (B, C vs A, χ2 test). Results of multivariable Cox regression analysis are present in Table 1. Table 1 Group A Group B Group C Age <80 years old Age between 80–90 years old Age ≥90 years old HR (95% CI) HR (95% CI) HR (95% CI) Female (y/n) 1.026; (0.851–1.238) 1.202 (0.874–1.654) 1.332; (0.428–4.146) Age in TLE (year) 1.021; (1.013–1.029) 1.053 (0.996–1.114) 0.997; (0.701–1.418) NYHA class (by one) 1.391; (1.240–1.561) 1.409 (1.134–1.750) 1.312; (0.698–2.466) LVEF (1%) 0.974; (0.967–0.980) 0.993 (0.982–1.005) 1.003; (0.947–1.063) Hypertension (y/n) 1.062; (0.889–1.268) 0.595 (0.428–0.828) 0.679; (0.203–2.271) Diabetes (y/n) 1.384; (1.152–1.662) 1.333 (0.951–1.868) 1.522; (0.398–5.821) Creatinin level (umol/l) 1.045; (1.020–1.070) 1.608 (1.385–1.866) 2.247; (0.704–7.171) Atrial fibrillation (y/n) 1.402; (1.169–1.682) 1.066 (0.783–1.451) 1.278; (0.380–4.296) ICD (y/n) 0.994; (0.825–1.198) 0.942 (0.618–1.437) 1.922; (0.419–8.830) Infectious indications (y/n) 1.137; (0.913–1.415) 1.014 (0.671–1.533) 1.104; (0.298–4.091) Lead related endocarditis 1.511; (1.174–1.945) 1.576 (1.004–2.474) 1.942; (0.385–9.804) Conclusion The survival of eighty-year-olds and ninety-year-olds did not differ between themselves in long term follow-up after TLE. There were no specific risk factors affecting the risk of mortality in long-term observation after TLE in nanogenarius

scholarly journals Hemodialysis Adequacy and Its Impact on Long-Term Patient Survival in Demographically, Socially, and Culturally Homogeneous Patients

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Reza Hekmat
Keyword(s):  
Cox Regression ◽  
Patient Survival ◽  
Underlying Disease ◽  
Chronic Hemodialysis ◽  
Historical Cohort ◽  
Cox Regression Analysis ◽  
Group A ◽  
One Year ◽  
Group B ◽  
Iranian Patients

Background. Impact of hemodialysis adequacy on patient survival is extensively studied. The current study compares the survival of chronic hemodialyzed, undocumented, uninsured, Afghan immigrant patients with that of a group of insured Iranian patients matched for underlying disease, age, weight, level of education, marital status, income, and number of comorbid conditions. Methods. Eighty chronic hemodialysis patients (mean age 42.8 ± 10.5 years) entered this historical cohort study in Mashhad, Iran, between January 2012 and January 2015. Half of the patients were undocumented, uninsured, Afghan immigrants (Group A) matched with forty insured Iranian patients (Group B). To compare the survival rate of the two patient groups, Kaplan–Meir survival analysis test was used. Results. Group A patients were underdialyzed with a weekly Kt/V which was significantly less in comparison with that of Group B (1.63 ± 0.63 versus 2.54 ± 0.12, p value = 0.01). While Group A’s number of hemodialysis sessions per week was fewer than that of Group B (1.45 ± 0.56 versus 2.8 ± 0.41, p value = 0.04), the mean of Kt/V in each hemodialysis session was higher in them, in comparison with Group B (1.43 ± 0.25 versus 1.3 ± 0.07, p value = 0.045). In Group B and Group A patients, one-year survival was 70% versus 50%, two-year survival was 55% versus 30%, and three-year survival was 40% versus 20%, respectively (p values = 0.04, 0.02 and 0.04, respectively). In Cox regression analysis, hemodialysis adequacy and uninsurance were factors impacting patients’ survival (OR = 1.193 and 0.333, respectively). Conclusions. Undocumented, uninsured, inadequately hemodialyzed, Afghan patients had a significantly lower one-, two-, and three-year survival as opposed to their Iranian counterparts, probably due to lack of insurance.

scholarly journals P1166DOES PERITONEAL PROTEIN LOSS AFFECT CARDIOVASCULAR MORTALITY OF PERITONEAL DIALYSIS PATIENTS ?

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Marios Theodoridis ◽  
Stylianos Panagoutsos ◽  
Ioannis Neofytou ◽  
Konstantia Kantartzi ◽  
Efthimia Mourvati ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Peritoneal Dialysis ◽  
Cardiovascular Mortality ◽  
Cox Regression ◽  
Dialysis Patients ◽  
Protein Loss ◽  
Cox Regression Analysis ◽  
Kaplan Meier ◽  
Group A ◽  
Group B

Abstract Background and Aims Peritoneal protein loss (PPL) through peritoneal effluent has been a well-recognized detrimental result of peritoneal dialysis (PD). The amount of protein lost will depend on dialysis time, protein size, its serum concentration and other factors including patients’ clinical status. Peritoneal protein loss may be a manifestation of endothelial dysfunction, as with another type of capillary protein leakage, microalbuminuria, a recognized endothelial dysfunction marker. The aim of this study was to retrospectively evaluate the influence of PPL on cardiovascular mortality of peritoneal dialysis patients Method This is a single center retrospective study of 84 PD patients (m=54, f=30) with mean age of 65.2±17 years, mean PD duration of 43.2±24.9 months conducted for the time period from 2006 to 2019 (13 years). The patients were divided into two groups according to the amount of protein excreted during the modified Peritoneal Equilibration Test (PET) procedure using PD solution of 3.86% DW, 2 Lt infusion volume for total time of 4 hours. The total amount of proteins excreted was calculate from PET by multiplying the concentration of proteins at the end of the test with the total volume of PD fluid at the same time. Group A excreted a total amount of proteins &lt; 1.55 gr (median value) at the end of PET test and Group B &gt; 1.55 gr. The cumulative all-cause and cardiovascular survival of the PD patients was calculated by Kaplan Meier while the possible effect of any parameter in survival rates was evaluated by using Cox Regression analysis Results There was not any statistically significant difference between the two groups according to PD duration, age, dialysis adequacy targets, Residual Renal Function(RRF), BMI, ultrafiltration volume during PET and their transport status. The cumulative all-cause survival using Kaplan-Meier analysis revealed no statistically significant deference between the two groups (Log Rank p=0.55) even though mortality risk was adjusted for several factors (Cox Regression). When cardiovascular survival, using Cox Regression analysis, was adjusted for age, sex, Diabetes, PD modality, dialysis Kt/V and RRF we found that Group A (with protein excretion &lt; 1.55 gr) had statistically significant better cardiovascular survival (p=0.029) compared to Group B. We confirm these results while trying to find among the total of our patients the possible risk factors for cardiovascular mortality. Using Cox Regression analysis, the amount of protein excreted during PET procedure and the type of PD solutions (high or low in GDPs) used were statistically significant (p=0.019 and p=0.04 respectively) independent risk factors for cardiovascular survival in our patients. Conclusion These results indicate that protein loss during peritoneal dialysis procedure has negative impact on cardiovascular mortality and survival of PD patients. Additionally, the use of PD solutions with low Glucose Degradation Products (GDPs) and AGEs may improve PD patient’s cardiovascular survival. Randomized interventional studies are encouraged to address the pathological concern of PPL in the future, namely its effects on cardiovascular conditions or its role as marker and effort to reduce PPL using ACE inhibitors or vit D should be considered only if it diminishes cardiovascular morbidity or mortality.

Thalidomide Based Regimens (TBR) for Relapsed/Refractory Multiple Myeloma Patients: Long Term Follow Up, Unmaintained Remissions and Disease Control after Subsequent Treatments.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4812-4812
Author(s):  
Maria Roussou ◽  
Efstathios Kastritis ◽  
Athanasios Anagnostopoulos ◽  
Evangelos Eleftherakis-Papaiakovou ◽  
Charis Matsouka ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Progression Free Survival ◽  
Free Survival ◽  
Refractory Multiple Myeloma ◽  
Long Term Follow Up ◽  
Group A ◽  
Pulse Dexamethasone ◽  
Group B

Abstract Introduction: The effectiveness of thalidomide based regimens (TBR) in patients with relapsed/refractory multiple myeloma is well established. However, there are still limited data regarding the long term follow up after such regimens and the outcome of patients when they progress and they receive further treatment. In order to answer these questions we evaluated a series of 114 patients with relapsed/refractory multiple myeloma who were treated with TBR. None of these patients had previously received thalidomide, bortezomib or lenalidomide. Patients and Methods: All patients were treated with thalidomide and dexamethasone with or without other oral agents. More specifically 41 patients had received continuous thalidomide and pulse dexamethasone, 25 patients clarithromycin, continuous thalidomide and pulse dexamethasone, 43 patients intermittent thalidomide, pulse dexamethasone and cyclophosphamide and 5 patients continuous thalidomide, pulse dexamethasone and cyclophosphamide. Type of treatment at the time of progression after TBR, response to this treatment and progression free survival were recorded for each patient. Moreover, patients who received novel agents after progression to TBR, were divided into 2 subgroups, according to their resistance to thalidomide. In group A, patients had refractory or progressive myeloma while on TBR or within 2 months after discontinuation of TBR. In group B, myeloma progressed more than 2 months after discontinuation of TBR. Results: Among the 114 patients, 41 had not responded to TBR and 73 (64%) had achieved at least a partial response. The median PFS for all patients was 8 months. As of June 2007, 10 patients remain without progression from 28 to 81 months (median 54 months). Eight patients remain off treatment and without progression for a median of 56 months (range 28–81). Patients who did not respond to or progressed after TBR were analyzed for further treatment and outcome. Thirty eight patients (37%) died before receiving further treatment, 23 patients (23%) received conventional chemotherapy and 41 patients (40%) received continuous thalidomide and dexamethasone +/− clarithromycin or cyclophosphamide (17 patients), bortezomib and dexamethasone (7 patients), melphalan-bortezomib-dexamethasone and intermittent thalidomide (12 patients) or lenalidomide with dexamethasone (5 patients). Among these 41 patients, 24 were classified in group A (thalidomide resistant) and 17 in group B. Overall 17 (41%) achieved at least partial response after retreatment with novel agent-based regimens. A response was observed in 46% of patients in group A and in 35% of patients in group B. The median progression free survival of the 41 patients who received retreatment with novel agents was 9.2 months and the median survival was 17 months. Among the 23 patients who received conventional chemotherapy only five (21%) patients responded and the progression free survival and the median survival were 5.3 and 10.2 months, respectively. Conclusions: After an oral TBR regimen 6 (5%) patients remain without treatment and free of progression for more than 4 years. A significant number of patients who progressed after TBR and who received further treatment which included a novel agent achieved a response, including several patients who were resistant to TBR.

Long-Term Outcomes and Safety of Continuous Lenalidomide Plus Dexamethasone (Len+Dex) Treatment in Patients (Pts) with Relapsed or Refractory Multiple Myeloma (RRMM)

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2929-2929 ◽  
Author(s):  
Meletios Athanasios Dimopoulos ◽  
Mohamad Hussein ◽  
Arlene S Swern ◽  
Donna M. Weber
Keyword(s):  
Dose Reduction ◽  
Median Duration ◽  
Cox Regression ◽  
Incidence Rates ◽  
Long Term Outcomes ◽  
Cox Regression Analysis ◽  
Β2 Microglobulin ◽  
Grade 3

Abstract Abstract 2929 Background: Two pivotal phase 3 trials (MM-009 and MM-010) randomized 704 pts to assess Len+Dex vs placebo plus dexamethasone (Dex) in RRMM. The results demonstrated the significant overall survival (OS) benefit of Len+Dex vs Dex (38.0 vs 31.6 mos; p =.045) despite crossover of 48% of Dex pts to the Len+Dex arm at unblinding or progression (Dimopoulos MA et al. Leukemia 2009;23 :2147-52). This is an analysis of the long-term outcomes and safety of continuous Len+Dex treatment. Methods: This retrospective analysis pooled pts treated with Len+Dex in MM-009 and MM-010, with a median follow-up of 48 mos for surviving pts. A subset of pts with progression-free survival (PFS) of ≥ 2 yrs was selected. Prognostic factors for PFS within this subgroup of pts were identified by incorporating all baseline covariates with a univariate p <.15 into multivariate Cox regression analyses, and all possible models were fitted using SAS 9.2. Adverse event (AE) management and dosing for pts with PFS ≥ 2 yrs was compared with that for all pts treated with Len+Dex in order to evaluate if differences in pt management could contribute to better clinical outcomes. Incidence rates for AEs were calculated using person-yrs of follow-up. Data from pts who received Len+Dex in MM-009 (up to July 23, 2008) and MM-010 (up to March 2, 2008) were included in this analysis. Results: Among all pts treated with Len+Dex (N = 353), a total of 64 pts (18%) achieved PFS ≥ 2 yrs. For these 64 pts, median age was 61 yrs (range 33–81 yrs), 48% received > 1 prior therapy, and 57% had β2-microglobulin levels of ≥ 2.5mg/L. All these pts achieved a ≥ partial response (PR), including 67% with a ≥ very good PR and 50% with a complete response. Median time to first response was 2.8 mos (range 1.9–18.2 mos) which is comparable to that of all pts treated with Len+Dex. Median duration of response was not reached vs 15.5 mos, respectively. With median follow-up of 49 mos, the 3-yr OS is 94% (95% confidence interval [CI] 88.06–99.94). In a multivariate Cox regression analysis, shorter PFS was predicted with higher baseline β2-microglobulin level (hazard ratio [HR] 1.07; 95% CI 1.02–1.12) and lower hemoglobin (HR 0.91; 95% CI 0.84–0.99), as well as a higher number of prior therapies (HR 1.18; 95% CI 1.02–1.37). The median duration of treatment was longer among pts with PFS ≥ 2 yrs vs all pts treated with Len+Dex (46.2 mos [range 11.3–58.3] vs 9.8 mos [range 3.8–24], respectively). A higher proportion of these pts had a dose reduction within 12 mos after start of therapy vs all pts treated with Len+Dex (57% vs 24%, respectively). Dex dose was reduced in 27% of pts with PFS ≥ 2 yrs. Among pts without Len dose reduction, 31% had Dex dose reduction within the first 4 cycles. Granulocyte colony-stimulating factor was administered for the management of neutropenia in 39% of pts with PFS ≥ 2 yrs vs 25% of all pts treated with Len+Dex. Low discontinuation rates due to AEs were observed in both groups (12.5% vs 18.7%, respectively). The incidence rates per 100 person-yrs for grade 3–4 AEs among pts with PFS ≥ 2 yrs vs all pts treated with Len+Dex (N = 353) were, respectively: neutropenia (14.9 vs 29), febrile neutropenia (0.9 vs 2.3), thrombocytopenia (2.6 vs 10.2), anemia (4.4 vs 9.5), infection (11.8 vs 20.9), deep vein thrombosis/pulmonary embolism (2.2 vs 8.9), fatigue (2.2 vs 5.5), neuropathy (1.8 vs 3.4), and gastrointestinal disorders (5.3 vs 9.7). The incidence rates per 100 person-yrs for second primary malignancies (SPMs) were similar to that of all pts treated with Len+Dex, respectively: myelodysplastic syndromes (0 vs 0.4), solid tumor (1.8 vs 1.3), and non-melanoma skin cancer (2.3 vs 2.4). These rates are comparable to those expected in people aged > 50 yrs generally (1.4 per 100 person-yrs) (Altekruse SF et al. SEER Cancer Statistics Review, 1975–2007). Conclusions: Long-term continuous therapy with Len+Dex has demonstrated efficacy and is generally well tolerated in pts with RRMM. Overall, 18% of patients treated with Len+Dex achieve a PFS of > 2 yrs. No increase in SPMs was observed with long term Len+Dex therapy. With appropriate AE management, the incidence rates of grade 3–4 AEs remain low. This analysis demonstrates the value of AE management and the need for appropriate dose-adjustment to maintain tolerability, allowing pts to remain on therapy for maximal benefit. Disclosures: Dimopoulos: Celgene Corporation: Consultancy, Honoraria. Hussein:Celgene Corporation: Employment. Swern:Celgene Corporation: Employment. Weber:Celgene Corporation: Honoraria, Research Funding.

scholarly journals Proactive Infliximab Monitoring Following Reactive Testing is Associated With Better Clinical Outcomes Than Reactive Testing Alone in Patients With Inflammatory Bowel Disease

2018 ◽  
Vol 12 (7) ◽  
pp. 804-810 ◽  
Author(s):  
Konstantinos Papamichael ◽  
Ravy K Vajravelu ◽  
Byron P Vaughn ◽  
Mark T Osterman ◽  
Adam S Cheifetz
Keyword(s):  
Inflammatory Bowel Disease ◽  
Treatment Failure ◽  
Bowel Disease ◽  
Cox Regression ◽  
Drug Discontinuation ◽  
Cox Regression Analysis ◽  
Loss Of Response ◽  
Group A ◽  
Inflammatory Bowel ◽  
Group B

Abstract Background and Aims Reactive testing has emerged as the new standard of care for managing loss of response to infliximab in inflammatory bowel disease [IBD]. Recent data suggest that proactive infliximab monitoring is associated with better therapeutic outcomes in IBD. Nevertheless, there are no data regarding the clinical utility of proactive infliximab monitoring after first reactive testing. We aimed to evaluate long-term outcomes of proactive infliximab monitoring following reactive testing compared with reactive testing alone in patients with IBD. Methods This was a retrospective multicenter cohort study of consecutive IBD patients on infliximab maintenance therapy receiving a first reactive testing between September 2006 and January 2015. Patients were divided into two groups; Group A [proactive infliximab monitoring after reactive testing] and Group B [reactive testing alone]. Patients were followed through December 2015. Time-to-event analysis for treatment failure and IBD-related surgery and hospitalization was performed. Treatment failure was defined as drug discontinuation due to either loss of response or serious adverse event. Results The study population consisted of 102 [n = 70, 69% with CD] patients [Group A, n = 33 and Group B, n = 69] who were followed for (median, interquartile range [IQR]) 2.7 [1.4–3.8] years. Multiple Cox regression analysis identified proactive following reactive TDM as independently associated with less treatment failure (hazard ratio [HR] 0.15; 95% confidence interval [CI] 0.05–0.51; p = 0.002) and fewer IBD-related hospitalizations [HR: 0.18; 95% CI 0.05–0.99; p = 0.007]. Conclusions This study showed that proactive infliximab monitoring following reactive testing was associated with greater drug persistence and fewer IBD-related hospitalizations than reactive testing alone.

scholarly journals Krebs von den Lungen 6 levels in COVID-19 ICU Patients are Associated with Mortality

2021 ◽  
Author(s):  
Giuliana Scarpati ◽  
Daniela Baldassarre ◽  
Graziella Lacava ◽  
Filomena Oliva ◽  
Gabriele Pascale ◽  
...  
Keyword(s):  
Cox Regression ◽  
Icu Patients ◽  
Cox Regression Analysis ◽  
Alveolar Epithelial ◽  
Type Ii Pneumocytes ◽  
Group A ◽  
Predictive Role ◽  
Fraction Of Inspired Oxygen ◽  
Group B

Rationale Krebs von den Lungen 6 (KL-6) is a high molecular weight mucin-like glycoprotein produced by type II pneumocytes and bronchial epithelial cells. Elevated circulating levels of KL-6 may denote disorder of the alveolar epithelial lining. Objective Aim of this study was to verify if KL-6 values may help to risk stratify and triage severe COVID-19 patients. Methods We performed a retrospective prognostic study on 110 COVID-19 ICU patients, evaluating the predictive role of KL-6 for mortality. Measurements and Main Results The study sample was divided in two groups related according to the median KL-6 value [Group A (KL-6 lower than the log-transformed median (6.73)) and Group B (KL-6 higher than the log-transformed median)]. In both linear and logistic multivariate analyses, ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (P/F) was significantly and inversely related to KL-6. Death rate was higher in group B than in group A (80.3 versus 45.9%) (p<0.001), Accordingly, the Cox regression analysis showed a significant prognostic role of KL-6 on mortality in the whole sample as well as in the subgroup with SOFA lower than its median value. Conclusions At ICU admission, KL-6 serum level was significantly lower in the survivors group. Our findings shown that, in severe COVID19 patients, elevated KL-6 was strongly associated with mortality in ICU.

scholarly journals Risk of brain herniation after craniotomy with lumbar spinal drainage: a propensity score analysis

2019 ◽  
Vol 130 (5) ◽  
pp. 1710-1720 ◽  
Author(s):  
Yasushi Motoyama ◽  
Tsukasa Nakajima ◽  
Yoshiaki Takamura ◽  
Tsutomu Nakazawa ◽  
Daisuke Wajima ◽  
...  
Keyword(s):  
Propensity Score ◽  
Cox Regression ◽  
Propensity Score Analysis ◽  
Control Group ◽  
Deep Approach ◽  
Brain Herniation ◽  
Cox Regression Analysis ◽  
Group A ◽  
Group B ◽  
Lumbar Spinal

OBJECTIVELumbar spinal drainage (LSD) during neurosurgery can have an important effect by facilitating a smooth procedure when needed. However, LSD is quite invasive, and the pathology of brain herniation associated with LSD has become known recently. The objective of this study was to determine the risk of postoperative brain herniation after craniotomy with LSD in neurosurgery overall.METHODSIncluded were 239 patients who underwent craniotomy with LSD for various types of neurological diseases between January 2007 and December 2016. The authors performed propensity score matching to establish a proper control group taken from among 1424 patients who underwent craniotomy and met the inclusion criteria during the same period. The incidences of postoperative brain herniation between the patients who underwent craniotomy with LSD (group A, n = 239) and the matched patients who underwent craniotomy without LSD (group B, n = 239) were compared.RESULTSBrain herniation was observed in 24 patients in group A and 8 patients in group B (OR 3.21, 95% CI 1.36–8.46, p = 0.005), but the rate of favorable outcomes was higher in group A (OR 1.79, 95% CI 1.18–2.76, p = 0.005). Of the 24 patients, 18 had uncal herniation, 5 had central herniation, and 1 had uncal and subfalcine herniation; 8 patients with other than subarachnoid hemorrhage were included. Significant differences in the rates of deep approach (OR 5.12, 95% CI 1.8–14.5, p = 0.002) and temporal craniotomy (OR 10.2, 95% CI 2.3–44.8, p = 0.002) were found between the 2 subgroups (those with and those without herniation) in group A. In 5 patients, brain herniation proceeded even after external decompression (ED). Cox regression analysis revealed that the risk of brain herniation related to LSD increased with ED (hazard ratio 3.326, 95% CI 1.491–7.422, p < 0.001). Among all 1424 patients, ED resulted in progression or deterioration of brain herniation more frequently in those who underwent LSD than it did in those who did not undergo LSD (OR 9.127, 95% CI 1.82–62.1, p = 0.004).CONCLUSIONSBrain herniation downward to the tentorial hiatus is more likely to occur after craniotomy with LSD than after craniotomy without LSD. Using a deep approach and craniotomy involving the temporal areas are risk factors for brain herniation related to LSD. Additional ED would aggravate brain herniation after LSD. The risk of brain herniation after placement of a lumbar spinal drain during neurosurgery must be considered even when LSD is essential.

Comparing carboplatin dose administered to the calculated dose using the Modification of Diet and Renal Disease (MDRD) equation

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 13003-13003
Author(s):  
J. L. Villano ◽  
L. Bressler ◽  
L. Radhakrishnan ◽  
S. Cuellar ◽  
S. S. Shord
Keyword(s):  
Serum Creatinine ◽  
Dose Reduction ◽  
Accurate Estimation ◽  
Mdrd Equation ◽  
Calculated Dose ◽  
Group A ◽  
Group B ◽  
Carboplatin Dose ◽  
Dose Reductions ◽  
Made In

13003 Background: Renal function assessment is vital for dosing of chemotherapy drugs. GFR is usually estimated by creatinine clearance (CrCl). The MDRD equation is thought to provide a more accurate estimation of GFR than the Cockcroft-Gault or 24-hour CrCl measurement. Although this formula has been validated in kidney disease, it has not been extensively studied in cancer patients. Methods: We retrospectively reviewed records for patients who received carboplatin from the University of Illinois at Chicago for a 4-year study period. General demographic information, carboplatin dose for cycles one to three, and common laboratory parameters at baseline and following cycles one to three were collected. The MDRD derived value of GFR was then used in the Calvert equation to calculate carboplatin dose. This calculated dose was compared to the actual dose administered in the first cycle. From this comparison, the records were divided into two groups: (A) actual vs. calculated dose ≥ 20% and (B) actual vs. calculated dose < 20%. We then assessed toxicity by determining the frequency in each group requiring dose reduction on the second cycle of carboplatin. Results: Data are available for 116 patient comparisons. 78 patient comparisons were in group B with agreement between actual vs. calculated MDRD dose. 38 were in group A with 36 having the actual dose being ≥ 20% less than the MDRD-calculated dose. Wilcoxin and Chi analysis reveals statistical significance for African American, women, lower serum creatinine, and older age for Group A. In Group A, cycle 2 dose reductions were made in 3 cases (8% and due to hematologic). In Group B, cycle 2 dose reductions were made in 12 cases. In 8 of these cases (10%), dose reductions were based on ANC, and in 4 cases dose reductions were made likely on the basis of changes in weight or creatinine. Conclusion: In the comparisons examined to date, differences in carboplatin doses due to different methods of calculation do not appear to significantly influence the frequency of dose reduction. Factors used in calculating MDRD such as age, sex, serum creatinine, and ethnicity were variables associated with ≥ 20% difference in actual vs. calculated MDRD dose. No significant financial relationships to disclose.

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