Fluid Accumulation During The Early Phases Of Hematopoietic Stem Cell Transplantation (HSCT) Is Associated With An Increased Risk Of Mortality and Complications

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4572-4572
Author(s):  
Erika MM Costa ◽  
Fernanda NC Santos ◽  
Erika Abdon Oliveira ◽  
Juliano Cordova Vargas ◽  
Karine Sampaio Nunes Barroso ◽  
...  
Keyword(s):  
Septic Shock ◽  
Respiratory Failure ◽  
Fluid Accumulation ◽  
Hematopoietic Stem ◽  
Icu Admission ◽  
Time Period ◽  
Risk Of Mortality ◽  
Increased Risk ◽  
Unrelated Donors ◽  
Early Phases

Introduction It has been previously reported that increased fluid accumulation during peripheral blood hematopoietic stem cell (HSC) mobilization is associated with poor outcome in patients with amyloidosis who undergo autologous HSCT. It is unknown whether increased fluid accumulation during the early phases of HSCT is associated with poor survival in patients undergoing HSCT for other diseases. Objective To determine the impact of fluid accumulation during conditioning and in the first 10 days post HSC infusion on survival and risk of complications of patients who underwent both autologous and allogeneic HSCT. Methods We retrospectively reviewed the medical charts of 257 consecutive patients who underwent HSCT at our institution from January, 2007 until December, 2012. Information on patients' body weight (BW) was measured daily, starting at admission. The highest BW recorded until HSC infusion (D0) and until the first 10 days post-SCT (D+10) was used to calculate the BW increase in relation to the baseline BW. A ROC curve was built to determine the best cut-off point in BW increase that predicted for mortality. Information on the incidence of post-transplant complications was extracted from the time period that patients were admitted for transplant until discharge from the hospital. Endpoints analyzed included the presence or absence of respiratory failure, acute renal failure, sinusoidal obstruction syndrome (SOS), septic shock and requirement of diuretic use, hemodialysis, mechanical ventilation and ICU admission. Overall survival (OS) was estimated from the time of HSCT until death, and surviving patients were censored at last follow-up. Variables entered into the multivariate Cox analysis were those with a p-value<0.10 in the univariate analysis. Statistical analysis was performed with STATA (v11.0) and alfa error was defined as 5%. Results Mean age was 39.4 years old (range <1 year-76 years) and 61% were male. HSC sources included autologous (47%), matched related donors (15%), matched unrelated donors (13%), cord blood units (19%) and mismatched related/unrelated donors (6%). Diagnosis included acute leukemia or chronic myeloid disorders (37%), lymphoma/multiple myeloma (42%) and non-malignant hematological disorders (21%).The results of the ROC curve defined the cut-point of 6% BW gain by D+10 as the best predictor for OS. A total of 69 patients (27%) had a BW increase ≥6% by D+10. This was associated with an increased risk of mortality, with a 100-days OS of 67% vs. 92% (HR 3.25, p<0.0001, 95% CI 2.04-5.18; Figure). A greater than 6% gain in BW by D+10 was also associated with an increased risk of developing SOS (31% vs. 6%; p<0.0001), septic shock (29% vs. 7%; p<0.0001), respiratory failure (35% vs. 9%; p<0.0001) and requiring diuretic use (91% vs. 71%; p<0.001), hemodialysis (13% vs. 4%, p=0.007), mechanical ventilation (33% vs. 9%; p<0.0001) and ICU admission (42% vs. 24%; p<0.0001). In a multivariate analysis considering age, diagnosis, type of SCT and sex, a ≥6% BW gain by D+10 was an independent variable associated with an increased risk of mortality (HR 3.28; p<0.0001; 95% CI 2.02-5.32). We next evaluated the prognostic impact of a ≥6% BW increase in the time period from admission until D0. Our results showed that it was similarly associated with an increased risk of mortality (HR 2.26; p=0.003; 95% CI 1.32-3.86), of developing SOS (32% vs. 9%; p<0.0001), respiratory failure (27%vs. 14%; p=0.04) and requiring hemodialysis (15% vs. 5%; p=0.01) and ICU admission (37% vs. 18%; p=0.008). After adjusting for age, sex, diagnosis and type of SCT, ≥6% BW gain by D0 was associated with an increased mortality (HR 1.94; p=0.026; 95% CI 1.08-3.48). Conclusion In our cohort of patients, fluid accumulation during the early stages of conditioning regimen and HSCT, reflected by a ≥6% increase in BW, was associated with an increased mortality and risk of developing severe complications. This may reflect the presence of increased endothelial damage, and further studies are needed to better clarify the mechanism behind weight gain during HSCT. Our results demonstrate that patients who have a ≥ 6% gain in BW by D0 and D+10 have an increased risk of complications, and more intensive monitoring of these patients is needed. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Acute Non-Infectious Complications of Pediatric Hematopoietic Stem Cell Transplantation: An in-Hospital Nationwide Study in the United States from 2001-2019

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 32-32
Author(s):  
Maria Alejandra Pereda ◽  
Sindhoosha Malay ◽  
Jignesh Dalal
Keyword(s):  
Mechanical Ventilation ◽  
Logistic Regression ◽  
Stem Cell ◽  
Respiratory Failure ◽  
Hematopoietic Stem Cell Transplantation ◽  
Infectious Complications ◽  
P Value ◽  
Early Complications ◽  
Hematopoietic Stem ◽  
Icu Admission

Introduction Hematopoietic stem cell transplantation (HSCT) is an effective treatment for malignant and non-malignant disorders and may be the only curative option for some diseases. Although overall outcomes of HSCT in pediatrics have improved HSCT is still associated with high morbidity and mortality. Toxicity following HSCT can virtually affect any organ and occur at different steps in the process. Early complications are to occur in the first 100 days post transplant. In this study we aimed to describe the frequency of early complications following HSCT and possible risk factors associated with increased ICU care and mortality. Methods With IRB approval, the Pediatric Health Information Systems (PHIS) database was queried to analyze information of all HSCT performed admitted between January 2001 and December 2019. The PHIS database is a comprehensive pediatric database that includes inpatient encounters for more than 52 children's hospitals. We extracted relevant ICD-9 and 10 diagnoses, procedure codes, and medications for each patient related to toxicities as outlined by the NCI. For Sinusoidal obstructive syndrome, graft failure and posterior reversible encephalopathy syndrome only ICD 10 code were reported. Clinical characteristics, demographics, procedures and medication of patients were presented using frequency and percentages for categorical variables with a Chi-square p-value (comparisons by ICU admission and Mortality). Univariate and multivariate logistic regression was performed with 'discharge mortality' and 'ICU admission' as primary outcomes. P-value of less than 0.05 or absence of 1 in the 95% confidence intervals was considered statistically significant. All statistical analyses were performed using SAS software, version 9.4 (SAS Institute, Cary, NC) and R software, version 4.0.0. Results A total of 13,538 patients met primary inclusion criteria of HSCT. Of these 6,938 transplants (51.2%) were performed to treat a malignant condition. 95.4% of these transplants were allogeneic and most of them performed within 2011 to 2019 (63.4%). Adolescents and Young adults accounted for 18.3% of patients and 8% of all HSCT patients passed away. The most common conditioning regimen reported was Busulfan and Cyclophosphamide (21.04%) and the most used GVHD prophylaxis was Methotrexate and Tacrolimus (21.1%). Common complications reported were acute kidney injury (14%), respiratory failure (12.8%) and acute GVHD (10%). From the patients that developed respiratory failure 90.5% were in the ICU, 80.9% required Mechanical ventilation and 49.6% died. 239 patients developed sinusoidal obstructive syndrome with 67.4% requiring ICU and 20.5% mortality. Defibrotide was used in 60.3% of these patients. Table 1 and 2 describe our findings and statistically significant results for ICU admission and discharge mortality. Logistic regression and multivariate analysis showed increased ICU admission and discharge mortality in AYA patients (OR 1.36, CI 1.20-1.53, p&lt;.0001 and OR 1.29, CI 1.03-1.64, p&lt;0.03, respectively). From 2009 to 2019 there is an increased OR for ICU admission post HSCT but significant decreased in discharge mortality. Mechanical ventilation was the strongest predictor for ICU admission and discharge mortality (OR 44.81, CI = 37.19-53.99, p&lt;.0001 and OR 31.23, CI = 23.57 - 41.38, p&lt;.0001, respectively), followed by dialysis (OR 5.74, CI = 3.98-8.27, p&lt;.0001 and OR 5.82, CI = 4.62-7.32, p&lt;.0001). Patients diagnosed with sinusoidal obstructive syndrome had 3.2 times OR for ICU (CI = 2.29-4.57, p&lt;.0001) but decreased OR for mortality (OR 0.62, CI 0.39-0.98, p=0.038). SCID and Mucopolysaccharidosis patients had increased OR for ICU admission but not for discharge mortality. Conclusion To our knowledge this is the largest multicenter database analysis describing acute non-infectious complications of pediatric HSCT. Survival of HSCT patients that developed SOS have improved since 2016 which may be reflecting the introduction of Defibrotide. Mechanical ventilation was the strongest predictor for mortality with almost 30 times increased in odds ratio. Mucopolysaccharidosis and SCID showed increased need for ICU care but decreased mortality suggesting improvement in intensive care unit management. Prospective studies are needed to better describe outcomes of HSCT patients as well as areas of possible improvement to increase overall survival. Disclosures No relevant conflicts of interest to declare.

Weight Gain in the First 10 Days after Hematopoietic Stem Cell Transplantation (HSCT) Is a Risk Factor for Early Mortality

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2471-2471 ◽  
Author(s):  
Lucila Nassif Kerbauy ◽  
Erika MM Costa ◽  
Juliano Cordova Vargas ◽  
Claudia Mac Donald Bley Nascimento ◽  
Joyce E Hyppolito ◽  
...  
Keyword(s):  
Risk Factor ◽  
Weight Gain ◽  
Conditioning Regimen ◽  
Early Mortality ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Increased Risk ◽  
Inflammatory State ◽  
Unrelated Donors ◽  
The Impact

Abstract Introduction: Hematopoietic stem cell transplantation (HSCT) is an effective treatment option for patients with hematological and neoplastic diseases. Despite recent improvements, HSCT is still associated with a significant risk of mortality. Determining risk factors for death within the first 100 days after HSCT could help to identify patients who would benefit from interventions in order to decrease that risk. We have previously reported that increased fluid accumulation during conditioning chemotherapy and in the early period after HSCT was associated with decreased survival (Costa EMM et al, ASH 2013Abstract #4512). Herein, we expand that series of patients and we further analyze the impact of weight gain on early (100-days) mortality in patients who underwent HSCT at our institution. Objective: To determine the impact of weight gain during the first 10 days post-HSCT on 100 days mortality. Methods:We retrospectively reviewed the medical charts of 331 patients who underwent HSCT at our institution from January, 2007 until December, 2013. Information on patients' body weight (BW) was measured daily, starting at admission. The highest BW recorded until until the first 10 days post-SCT (D+10) was used to calculate the BW increase in relation to the baseline BW. Based on our previous study, we used a cutoff of 6% gain in BW to identify a group of patients with increased risk of complications. The primary endpoint was mortality within 100 days post HSCT. Overall survival (OS) was estimated from the time of HSCT until death, and surviving patients were censored at last follow-up. A logistic regression model and a Cox model were fit to determine variables that predicted death within 100 days and OS, respectively. Statistical analysis was performed with STATA (v11.0) and alfa error was defined as 5%. Results: Median age was 43 years old (range <1 year-76 years) and 60% were male. HSC sources included autologous (46%), matched related donors (16%), matched unrelated donors (12%), cord blood units (16%) and mismatched related/unrelated donors (10%). Diagnosis included acute leukemia or chronic myeloid disorders (34%), lymphoma/multiple myeloma (42%) and non-malignant hematological disorders (24%). Twenty-one percent of patients had a ≥6% gain in BW until the first 10 days post-HSCT. These patients had developed an increased inflammatory state after the start of the conditioning regimen: there was no difference in baseline levels of C-reactive protein (4.8 mg/L vs. 7.4, p=0.37), but by D+10 patients who gained more BW had higher CRP (116.7 mg/L vs. 178.6 mg/L; p=0.01). Patients with increased gain in BW until D+10 had a decreased OS (HR 2.33, p<0.0001, 95% CI 1.45-3.73). The mortality within 100 days was 47% in the increased BW vs. 17% in the control group (p<0.0001). Among 18 patients who died within 100 days and had a ≥6% BW gain by D+10, causes of death included pneumonia (N=4), septic shock (N=9), fungal endocarditis (N=1), ischemic stroke (N=1) and disease progression (N=3). In a logistic regression analysis, after adjusting for age, sex, diagnosis and type of SCT, a ≥6% BW gain by D10 was associated with an increased risk of being dead within 100 days (coefficient 1.75; p<0.0001; 95% CI 0.90-2.61). Similarly, in a multivariate Cox analysis after adjusting for age, sex, diagnosis and type of SCT, a ≥6% BW gain by D10 was an independent risk factor for survival (HR 2.72, p<0.0001, 95% CI 1.65-4.48). A landmark analysis at D+100 revealed that the negative impact of weight gain by D+10 on survival was restricted to the first 100 days, as after this time point there was no survival difference between the two groups (HR 1.35; p=0.41; 95% CI 0.65-2.83). Conclusion: A ≥6% BW gain by D+10 is a risk factor for early mortality in both autologous and allogeneic HSCT. The most common cause of death in these patients is infectious-related complications. An increase in BW is related to the development of an inflammatory state, probably induced by the conditioning regimen. BW gain is a simple variable that can be easily used to determine prognosis of patients post-allogeneic HSCT, and further studies are needed to determine its etiology. Disclosures No relevant conflicts of interest to declare.

scholarly journals Evaluation of admission serum magnesium levels in patients with septic shock and its correlation with outcome

2019 ◽  
Vol 7 (1) ◽  
pp. 155
Author(s):  
Akshay R. Khare ◽  
Vishwanath C. Patil ◽  
Jignesh N. Shah ◽  
Shivakumar S. Iyer
Keyword(s):  
Septic Shock ◽  
Sofa Score ◽  
Serum Magnesium ◽  
Length Of Hospital Stay ◽  
Standard Of Care ◽  
Suspected Infection ◽  
Time Period ◽  
Increased Risk ◽  
Standard Of Care Treatment ◽  
Organ Dysfunctions

Background: Admission hypomagnesemia has been linked with an increased risk of septic shock. The purpose of this study was to evaluate admission serum magnesium levels in patients with septic shock and to determine its correlation with the outcomes.Methods: It was a prospective observational study. Total 50 patients fitting the Sepsis-3 definition between time period of June 2017 to November 2018 were included in the study. Patients with suspected infection were identified at the bedside with qSOFA. Admission serum magnesium levels was measured for all patients included. APACHE II scores were calculated at the end of 24 hours after admission. Routine standard of care treatment was provided to all patients. The patients were monitored for organ dysfunctions based on daily SOFA scores, ventilator free days, vasopressors free days, dialysis free days, length of intensive care unit stay, length of hospital stay. The data was analysed using Statistical Package for Social Sciences for MS Windows.Results: In this study hypomagnesemia was prevalent in 18%, normomagnesemia in 62% and hypermagnesemia in 20% of total included patients. The mean vasopressor free days in Hypomagnesemia group (7.11±12.79 days) were higher than those in normomagnesemic patients (5.06±5.51 days) and hypermagnesemia patients (1.70±3.09 days). Out of total 50 patients 18 died and 32 recovered. 11 patients out of 32 who recovered had abnormal admission serum magnesium levels whereas 8 pts out of 18 who died had abnormal admission serum magnesium levels.  SOFA score in hypomagnesemic patients admitted with septic shock compared with those of normomagnesemic and hypermagnesemic patients was statistically significant.Conclusions: Author did not find any statistically significant correlation between admission magnesium levels in septic shock patients and outcomes although SOFA score was higher in hypomagnesemic patients admitted with septic shock compared with those of normomagnesemic and hypermagnesemic patients. Serum magnesium may not truly reflect body’s magnesium status. RBC magnesium may need to be studied to see whether it is a more reliable biomarker.

scholarly journals Recent advances in the pathophysiology and management of sepsis: a review

2021 ◽  
Vol 22 (2) ◽  
pp. 133-145
Author(s):  
B.A. Adegboro ◽  
J. Imran ◽  
S.A. Abayomi ◽  
E.O. Sanni ◽  
S.A. Biliaminu
Keyword(s):  
Septic Shock ◽  
Sofa Score ◽  
Clinical Status ◽  
Altered Mental Status ◽  
Risk Of Mortality ◽  
Increased Risk ◽  
Acute Increase ◽  
Haematological Changes ◽  
Definition Of ◽  
Sepsis And Septic Shock

Sepsis is a syndrome consisting of physiological, pathological and biochemical anomalies caused by infectious agents. It causes clinical organ dysfunction, which is identified by an acute increase in the Sequential (sepsis-related) Organ Failure Assessment (SOFA) score of two or more points. SOFA score is a score of three components that can be easily used at the bedside to track the clinical status of a patient while on admission, and these are altered respiratory rate of ≥ 22 breaths/minute, altered mental status, and systolic blood pressure of ≤ 100 mmHg. A patient with SOFA score of ≥ 2 has an attributable 2 - 25-fold increased risk of mortality compared to a patient with SOFA score of ˂ 2. This present review provides information on the new definition of sepsis and septic shock, aetiology, pathophysiology, biochemical, pathological and haematological changes, morbidity and mortality parameters, management, andprognostic factors in patients with sepsis. Key words: Sepsis, septic shock, SOFA score, pathophysiology, management bundles

scholarly journals Risk Factors for ICU Admission, Mechanical Ventilation and Mortality in Hospitalized Patients with COVID-19 in Hubei, China.

2020 ◽  
Author(s):  
Hong Gang Ren ◽  
Xingyi Guo ◽  
Kevin Blighe ◽  
Fang Zhu ◽  
Janet Martin ◽  
...  
Keyword(s):  
Risk Factors ◽  
Mechanical Ventilation ◽  
Severe Disease ◽  
Current Smoker ◽  
Hospitalized Patients ◽  
Total Leukocyte Count ◽  
Mechanically Ventilated ◽  
Icu Admission ◽  
Risk Of Mortality ◽  
Increased Risk

Purpose: To examine the risk factors for Intensive Care Unit (ICU) admission, mechanical ventilation and mortality in hospitalized patients with COVID-19. Methods: This was a retrospective cohort study including 432 patients with laboratory-confirmed COVID-19 who were admitted to three medical centers in Hubei province from January 1st to April 10th 2020. Primary outcomes included ICU admission, mechanical ventilation and death occurring while hospitalized or within 30 days. Results: Of the 432 confirmed patients, 9.5% were admitted to the ICU, 27.3% required mechanical ventilation, and 33.1% died. Total leukocyte count was higher in survivors compared with those who died (8.9 vs 4.8 x 109/l), but lymphocyte counts were lower (0.6 vs 1.0 x 109/l). D-dimer was significantly higher in patients who died compared to survivors (6.0ug/l vs 1.0ug/l, p<0.0001. This was also seen when comparing mechanically versus non-mechanically-ventilated patients. Other significant differences were seen in AST, ALT, LDH, total bilirubin and creating kinase. The following were associated with increased odds of death: age > 65 years (adjusted hazard ratio (HR 2.09, 95% CI 1.02-4.05), severe disease at baseline (5.02, 2.05-12.29), current smoker (1.67, 1.37-2.02), temperature >39o C at baseline (2.68, 1.88-4.23), more than one comorbidity (2.12, 1.62-3.09), bilateral patchy shadowing on chest CT or X-ray (3.74, 1.78-9.62) and organ failure (6.47, 1.97-26.23). The following interventions were associated with higher CFR: glucocorticoids (1.60, 1.04-2.30), ICU admission (4.92, 1.37-17.64) and mechanical ventilation (2.35, 1.14-4.82). Conclusion: Demographics, including age over 65 years, current smoker, diabetes, hypertension, and cerebrovascular disease, were associated with increased risk of mortality. Mortality was also associated with glucocorticoid use, mechanical ventilation and ICU admission. Take-Home Message: COVID-19 patients with risk factors were more likely to be admitted into ICU and more likely to require mechanical ventilation.

Ocena częstości występowania zakażeń wirusami hepatotropowymi u pacjentów poddanych allogenicznej transplantacji krwiotwórczych komórek macierzystych od dawcy niespokrewnionego

2018 ◽  
Vol 21 (1A) ◽  
Author(s):  
Mirosław Markiewicz ◽  
Ewa Rzenno ◽  
Agnieszka Karolczyk ◽  
Małgorzata Stachowicz ◽  
Monika Dzierżak-Mietła ◽  
...  
Keyword(s):  
Viral Infections ◽  
Significant Proportion ◽  
Hematopoietic Stem ◽  
Increased Risk ◽  
Serological Status ◽  
Before And After ◽  
History Of ◽  
Unrelated Donors ◽  
Allogenic Transplantation ◽  
The Subject

Introduction. The broad indications for allogenic transplantation of hematopoietic stem cells (allo-HSCT) and the use of immunosuppression after transplantation pose a risk of frequent occurrence of viral infections. Aim. The subject of the work is the analysis of serological status and prevalence of primarily (HBV, HCV) and secondarily (CMV, EBV) hepatotropic viruses in the group of patients treated with allo-HSCT from unrelated donors and assessment of the usefulness of serological and biomolecular methods in virological diagnostics both before and after transplantation. Material and methods. The study included 157 patients after allo-HSCT performed due to hematopoietic system diseases in the period 01.2015-03.2017. Results. The presence of anti-HBc and anti-EBV antibodies in the IgM class was demonstrated in 6 and 2.5% of patients before transplantation, in which DNA testing excluded presence of the viral load what allowed to perform the transplantation. Reactivation of HBV-DNA after transplantation was found in two patients with a long history of hepatitis B. In the post-transplant period, EBV viremia was detected in 31% of patients and CMV in 39% of patients. The frequency of CMV reactivation varied depending on the initial serological status of the donor-recipient pairs prior to transplantation. The reactivation of EBV and CMV had an effect on the survival of the patients and often occurred simultaneously. There was no case of HCV infection. Conclusions. Molecular studies of hepatotropic viruses prior to allo-HSCT are justified in the presence of serological markers suggesting the possibility of infection, which most often concerns HBV and EBV. Examination of CMV-DNA and EBV-DNA after allo-HSCT enables to detect reactivation of the virus in a significant proportion of patients, which is associated with an increased risk of adverse course of the disease. CMV viremia, the detection of which enables the implementation of proper treatment, occurs most frequently in patients whose serological status of CMV before transplantation was positive.

Increased Risk of Mortality With Hypoalbuminemia and Albumin Transfusion in Patients With Septic Shock in a Single Institution

CHEST Journal ◽  
2016 ◽  
Vol 150 (4) ◽  
pp. 367A
Author(s):  
Brian Garnet ◽  
Martin Aldana-Campos ◽  
Varun Shah ◽  
Mohammad Elballat ◽  
Atif Shah ◽  
...  
Keyword(s):  
Septic Shock ◽  
Single Institution ◽  
Risk Of Mortality ◽  
Increased Risk

scholarly journals RAAS blockers and region-specific variations in COVID-19 outcomes: findings from a systematic review and meta-analysis

2020 ◽  
Author(s):  
Upinder Kaur ◽  
Sankha Shubhra Chakrabarti ◽  
Tejas K Patel
Keyword(s):  
Mechanical Ventilation ◽  
Meta Analysis ◽  
Kidney Injury ◽  
Final Analysis ◽  
Chinese Patients ◽  
Mortality Data ◽  
Steroid Use ◽  
Icu Admission ◽  
Risk Of Mortality ◽  
Increased Risk

Background: Coronavirus disease 2019 (COVID-19) has evolved as a global crisis with high mortality seen in elderly and people with cardiometabolic diseases. The use of renin angiotensin aldosterone system (RAAS) blockers in these patients is known to enhance the expression of ACE-2, the chief binding receptor of SARS-CoV-2 and may potentially enhance infectivity. Objective: To provide a pooled estimate of the effect of RAAS blocker usage on COVID-19 outcomes. Data Sources: An electronic literature search was performed for published (using MEDLINE/PubMed and Google Scholar) and preprint (using bioRxiv and medRxiv) studies of interest. The last search was conducted on 9th July 2020. Study Selection: Studies reporting data on RAAS blocker use and COVID-19 mortality and severity were included in the review. Data Extraction and Synthesis: Mortality data and severity data including hospitalization, intensive care unit (ICU) admission, invasive ventilation, steroid use and acute kidney injury (AKI) were recorded. Pooled Odds ratio (OR) estimates were reported with 95% CIs and level of heterogeneity (I2). Main Outcomes and Measures: Odds of mortality in users of RAAS blockers with respect to non-users was the primary outcome. Odds of severity, hospitalization, ICU admission, mechanical ventilation, steroid use, and AKI in users with respect to non-users of RAAS blockers were the secondary outcomes. Results: Of 1348 articles identified, 48 published studies were included in the final analysis, with a total of 26432 patients from 31 studies included in mortality analysis and 20127 patients from 23 studies included in severity analysis. Majority of the studies (41.6%) were from China. No increased risk of mortality (Pooled OR 0.91 (0.65-1.26), I2=89%) or severity (Pooled OR 1.08 (0.79-1.46), I2=88%) was seen with RAAS blockers. The drug class was protective in hypertension (pooled OR 0.63 (0.46-0.86), I2=58%). Severity of COVID-19 outcomes was found to be high for Europeans (Pooled OR 2.08 (1.52-2.85), I2=77%) and US patients (Pooled OR 1.87 (1.62-2.17) in users of RAAS-blockers. A nearly 4 times higher risk of hospitalization, two times higher risk of ICU admission and mechanical ventilation was observed in US patients on RAAS blockers. No net effect on mortality and severity outcomes was seen in Chinese patients. RAAS blocker usage did not have any effect on corticosteroid use and AKI in Chinese patients. Conclusions and Relevance: Use of RAAS blockers is not associated with increased risk of mortality in COVID-19 patients. Reduced mortality is seen in hypertensive patients with COVID-19 and therefore the drugs should be continued in this subset. US and European patients are at higher risk of severe outcomes. Pharmacogenomic differences may explain the ethnicity related variations.

Graft Failure In Reduced Intensity Conditioning Allogeneic Hematopoietic Stem Cell Transplantation

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4559-4559
Author(s):  
Richard Olsson ◽  
Daniel Moreno Berggren ◽  
Olle Ringden ◽  
Jonas Mattsson ◽  
Mats Remberger
Keyword(s):  
Risk Factors ◽  
Stem Cell ◽  
Solid Tumors ◽  
Graft Failure ◽  
Reduced Intensity Conditioning ◽  
Hematopoietic Stem ◽  
Gvhd Prophylaxis ◽  
Increased Risk ◽  
Unrelated Donors ◽  
Reduced Intensity

A decade ago reduced intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (allo-HSCT) was successfully introduced to facilitate transplantation in patients with co-morbidities. In contrast to myeloablative conditioning regimens RIC transplants are associated with less toxicity and thus preferred in the elderly population. However, there are also disadvantages with RIC such as the increased risk of graft failure caused by rejection by remnant recipient T-cells at transplant, which often results in mixed chimerism during the first months post-transplant. Here, we present risk factors for graft failure in all first RIC allo-HSCTs performed at our center from 1995 to mid-2010 (n=357). Graft failure was defined as >95% recipient T-cells any time after engraftment or reinfusion of donor cells due to >50% recipient cells with no clinical or laboratory signs of relapse. Thirty-six patients (10%) experienced graft failure. The median age of the patients was 51 and 57% were males. In univariate analysis, graft failure was 3-fold increased in male compared to female patients (15% versus 4%; P<0.01). Furthermore, patients with non-malignant disorders (26% versus 2%; P<0.01) and solid tumors (20% vs. 2%; P<0.01) had an increased risk of graft failure when compared to acute leukemia. Graft versus host disease (GVHD) prophylaxis using cyclosporine A (CSA) in combination with mycophenolate mofetil (MMF) resulted in increased numbers of graft failure when compared to our standard regimen with CSA and methotrexate (18% vs. 5%; P<0.01). The graft failure rate was the lowest among HLA-identical sibling donors (6%), slightly higher in 8/8 matched unrelated donors (10%), and the highest in 6/6 matched unrelated donors (18%; P<0.01). Total nucleated cell (TNC) dose was also important with less graft failures when the TNC dose was >10 x 108/kg, whereas CD34+ cell dose had no impact on graft failure (P=0.15). Moreover, in univariate analyses year of transplant, donor sex, cell source, CMV mismatch, ABO mismatch, or pre-planned G-CSF did not influence graft failure rates (P>0.05). In multivariate analysis (Table 1), solid tumors were associated with markedly increased risk of graft failure (RR=10.95; P=0.03), whereas there was a tendency towards increased graft failure risk in non-malignant disorders (RR=8.01; P=0.05). Graft failures were also increased in male recipients (RR=3.27; P<0.01), in grafts with a TNC dose less than 10 x 108/kg (RR=2.17; P=0.03), when using MMF containing GVHD prophylaxis (RR=3.61; P<0.01), and in transplants with HLA match less than 8/8 (RR=4.94; P<0.01). In conclusion, graft failure is augmented in male recipients, and associated with diseases which usually do not receive high-dose chemotherapy pre-transplant such as solid tumors. HLA mismatch as well as TNC dose and GVHD prophylaxis were also important risk factors for graft failure in the present study.Table 1Multivariate analysis of risk factors for graft failure in reduced intensity conditioning allo-HSCT.CharacteristicsNRR95% CIP-valueNo of patients357Recipient sexFemale1531Male2043.271.35-7.93<0.01DiseaseAcute leukemiaa661CML276.810.70-66.310.10CLL225.380.55-52.630.15Lymphoma361.540.10-24.830.76MDS324.260.38-47.190.24MPD187.400.67-82.360.10Multiple myeloma2300-82.361Aplastic anemia382.540.25-26.210.43Non-malignant disorders348.010.96-66.800.05Solid tumors6110.951.34-89.170.03HLA matchHLA-identical sibling1561Unrelated donor 6/6454.941.84-13.24<0.01Unrelated donor 8/81232.160.90-5.180.09Other matched300-13.241Other mismatched303.301.18-9.240.02Total nucleated cell dose (x108/kg)0-58615-10920.540.24-1.220.1410-14870.370.15-0.940.04>14870.240.08-0.750.01GVHD profylaxisCSA+MTX2401CSA+Pred142.160.63-7.400.22CSA+MMF403.611.38-9.44<0.01Fk 506 +Rapamune451.320.43-4.080.63Other176.242.27-17.16<0.01aAML (n=60) and ALL (n=6). Disclosures: No relevant conflicts of interest to declare.

Competing causes of death in patients with neuroendocrine tumor.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e23009-e23009
Author(s):  
Soon Khai Low ◽  
Bao Long Hoang Trong ◽  
Nourelhoda Sami Bahaie ◽  
Dimitrios Giannis ◽  
Gehad Mohamed Tawfik ◽  
...  
Keyword(s):  
Causes Of Death ◽  
Heart Diseases ◽  
Unknown Primary ◽  
Relative Risks ◽  
Time Period ◽  
Risk Of Mortality ◽  
Increased Risk ◽  
Standardized Mortality Ratios ◽  
Competing Causes ◽  
Using Data

e23009 Background: Increasing survival of patients with neuroendocrine tumors (NETs) may be associated with higher risk of mortality due to causes other than the primary NET, namely the competing causes of death (CCD). Therefore, our study focused on comprehensively investigating the magnitude of the CCD on the overall NET mortality and the associated demographic, clinicopathologic and treatment factors using data from the Surveillance, Epidemiology, and End Results (SEER) database. Methods: Patients with histologically confirmed primary NET diagnosed from 1973 through 2015 were identified using the SEER-9 registries for subsequent data collection and analysis. CCD were stratified and analyzed using standardized mortality ratios (SMRs) as measures of the relative risks of mortality for NET patients in comparison to the general population in the US adjusted by age, sex and race over the same time period. Competing risk regression analysis was performed using Fine and Gray multivariate regression model. Results: A total of 29,981 NET patients were included, 5481 (42.5%) of which deceased due to CCD. Overall SMR attributed to CCD was 2.50 [95% Confidence interval (CI): 2.43–2.56]. The SMR of non-cancer CCD was 2.65 (95% CI:2.58–2.73) and that of SPN was 1.91 (95% CI:1.79–2.04). Heart diseases and other cardiovascular diseases accounted for approximately half of all non-cancer CCD. SPN mortality accounted for 16.1% of CCD, with lung and bronchus cancer being the most prevalent. Stratification by the year of diagnosis revealed a drastic rise in CCD was observed in the last decade between 2005 and 2015, during which the SMR peaked. Advanced age, black race, small intestinal and gastric NETs, and cancer-directed surgery were significantly associated with an increased risk of CCD (p<0.001). Interestingly, female sex, pancreatic NETs, recto-anal NETs, NETs of unknown primary site, race other than white and black, distant and regional spread, chemotherapy and radiotherapy were significantly associated with a decrease in the incidence of CCD. Conclusions: CCD play an increasingly significant role in NET mortality in recent years, especially for those with higher risk of CCD. Further prospective studies are needed to evaluate the association of NETs with these CCD.

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