Loncastuximab tesirine in relapsed/refractory high-grade B-cell lymphoma: a subgroup analysis from the LOTIS-2 study

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GRFS and CRFS in alternative donor hematopoietic cell transplantation for pediatric patients with acute leukemia.

We report graft-versus-host disease (GVHD)-free relapse-free survival (GRFS) (a composite end point of survival without grade III-IV acute GVHD [aGVHD], systemic therapy-requiring chronic GVHD [cGVHD], or relapse) and cGVHD-free relapse-free survival (CRFS) among pediatric patients with acute leukemia (n = 1613) who underwent transplantation with 1 antigen-mismatched (7/8) bone marrow (BM; n = 172) or umbilical cord blood (UCB; n = 1441). Multivariate analysis was performed using Cox proportional hazards models. To account for multiple testing, P \u3c .01 for the donor/graft variable was considered statistically significant. Clinical characteristics were similar between UCB and 7/8 BM recipients, because most had acute lymphoblastic leukemia (62%), 64% received total body irradiation-based conditioning, and 60% received anti-thymocyte globulin or alemtuzumab. Methotrexate-based GVHD prophylaxis was more common with 7/8 BM (79%) than with UCB (15%), in which mycophenolate mofetil was commonly used. The univariate estimates of GRFS and CRFS were 22% (95% confidence interval [CI], 16-29) and 27% (95% CI, 20-34), respectively, with 7/8 BM and 33% (95% CI, 31-36) and 38% (95% CI, 35-40), respectively, with UCB (P \u3c .001). In multivariate analysis, 7/8 BM vs UCB had similar GRFS (hazard ratio [HR], 1.12; 95% CI, 0.87-1.45; P = .39), CRFS (HR, 1.06; 95% CI, 0.82-1.38; P = .66), overall survival (HR, 1.07; 95% CI, 0.80-1.44; P = .66), and relapse (HR, 1.44; 95% CI, 1.03-2.02; P = .03). However, the 7/8 BM group had a significantly higher risk for grade III-IV aGVHD (HR, 1.70; 95% CI, 1.16-2.48; P = .006) compared with the UCB group. UCB and 7/8 BM groups had similar outcomes, as measured by GRFS and CRFS. However, given the higher risk for grade III-IV aGVHD, UCB might be preferred for patients lacking matched donors. © 2019 American Society of Hematology. All rights reserved

Determinants of short and long term functional recovery after hospitalization for community-acquired pneumonia in the elderly: role of inflammatory markers

BACKGROUND: Hospitalization for older patients with community-acquired pneumonia (CAP) is associated with functional decline. Little is know about the relationship between inflammatory markers and determinants of functional status in this population. The aim of the study is to investigate the association between tumor necrosis factor (TNF)-α, C-reactive protein (CRP) and Activities of Daily Living, and to identify risk factors associated with one year mortality or hospital readmission. METHODS: 301 consecutive patients hospitalized for CAP (mean age 73.9 ± 5.3 years) in a University affiliated hospital over 18 month period were included. All patients were evaluated on admission to identify baseline demographic, microbiological, cognitive and functional characteristics. Serum levels for TNF-α and CRP were collected at the same time. Reassessment of functional status at discharge, and monthly thereafter till 3 months post discharge was obtained and compared with preadmission level to document loss or recovery of functionality. Outcome was assessed by the composite endpoint of hospital readmission or death from any cause up to one year post hospital discharge. RESULTS: 36% of patients developed functional decline at discharge and 11% had persistent functional impairment at 3 months. Serum TNF-α (odds ratio [OR] 1.12, 95% CI 1.08–1.15; p < 0.001) and the Charlson Index (OR = 1.39, 95% CI 1.14 to 1.71; p = 0.001) but not age, CRP, or cognitive status were independently associated with loss of functionality at the time of hospital discharge. Lack of recovery in functional status at 3 months was associated with impaired cognitive ability and preadmission comorbidities. In Cox regression analysis, persistent functional impairment at 3 months, impaired cognitive function, and the Charlson Index were highly predictive of one year hospital readmission or death. CONCLUSION: Serum TNF-α levels can be useful in determining patients at risk for functional impairment following hospitalization from CAP. Old patients with impaired cognitive function and preexisting comorbidities who exhibit delay in functional recovery at 3 months post discharge may be at high risk for hospital readmission and death. With the scarcity of resources, a future risk stratification system based on these findings might be proven helpful to target older patients who are likely to benefit from interventional strategies

Fiberoptic endoscopic evaluation of swallowing in intensive care unit patients

Aspiration in critically ill patients frequently causes severe co-morbidity. We evaluated a diagnostic protocol using routine FEES in critically ill patients at risk to develop aspiration following extubation. We instructed intensive care unit physicians on specific risk factors for and clinical signs of aspiration following extubation in critically ill patients and offered bedside FEES for such patients. Over a 45-month period, we were called to perform 913 endoscopic examinations in 553 patients. Silent aspiration or aspiration with acute symptoms (cough or gag reflex as the bolus passed into the trachea) was detected in 69.3% of all patients. Prolonged non-oral feeding via a naso-gastric tube was initiated in 49.7% of all patients. In 13.2% of patients, a percutaneous endoscopic gastrostomy was initiated as a result of FEES findings, and in 6.3% an additional tracheotomy to prevent aspiration had to be initiated. In 59 out of 258 patients (22.9%), tracheotomies were closed, and 30.7% of all 553 patients could be managed with the immediate onset of an oral diet and compensatory treatment procedures. Additional radiological examinations were not required. FEES in critically ill patients allows for a rapid evaluation of deglutition and for the immediate initiation of symptom-related rehabilitation or for an early resumption of oral feeding

The Surviving Sepsis Campaign: results of an international guideline-based performance improvement program targeting severe sepsis

Objective: The Surviving Sepsis Campaign (SSC or “the Campaign”) developed guidelines for management of severe sepsis and septic shock. A performance improvement initiative targeted changing clinical behavior (process improvement) via bundles based on key SSC guideline recommendations on process improvement and patient outcomes. Design and setting: A multifaceted intervention to facilitate compliance with selected guideline recommendations in the ICU, ED, and wards of individual hospitals and regional hospital networks was implemented voluntarily in the US, Europe, and South America. Elements of the guidelines were “bundled” into two sets of targets to be completed within 6 h and within 24 h. An analysis was conducted on data submitted from January 2005 through March 2008. Main results: Data from 15,022 subjects at 165 sites were analyzed to determine the compliance with bundle targets and association with hospital mortality. Compliance with the entire resuscitation bundle increased linearly from 10.9% in the first site quarter to 31.3% by the end of 2 years (P < 0.0001). Compliance with the entire management bundle started at 18.4% in the first quarter and increased to 36.1% by the end of 2 years (P = 0.008). Compliance with all bundle elements increased significantly, except for inspiratory plateau pressure, which was high at baseline. Unadjusted hospital mortality decreased from 37 to 30.8% over 2 years (P = 0.001). The adjusted odds ratio for mortality improved the longer a site was in the Campaign, resulting in an adjusted absolute drop of 0.8% per quarter and 5.4% over 2 years (95% CI, 2.5–8.4%). Conclusions: The Campaign was associated with sustained, continuous quality improvement in sepsis care. Although not necessarily cause and effect, a reduction in reported hospital mortality rates was associated with participation. The implications of this study may serve as an impetus for similar improvement efforts.Electronic supplementary material The online version of this article (doi:10.1007/s00134-009-1738-3) contains supplementary material, which is available to authorized users

Obesity and smoking are factors associated with poor prognosis in patients with bacteraemia

BACKGROUND: Bacteraemia is still a major cause of case fatality in all age groups. Our aim was to identify the major underlying conditions constituting risk factors for case fatality in bacteraemia patients. METHODS: The study involved 149 patients (79 male and 70 female) with bacteraemia caused by Staphylococcus aureus (S. aureus) (41 patients), Streptococcus pneumoniae (Str. pneumoniae) (42 patients), β-hemolytic streptococcae (β-hml str.) (23 patients) and Eschericia coli (E. coli) (43 patients). Underlying diseases, alcohol and tobacco consumption and body mass index (BMI) were registered. Laboratory findings and clinical data were registered on admission and 6 consecutive days and on day 10–14. Case fatality was studied within 30 days after positive blood culture. Associations between underlying conditions and case fatality were studied in univariate analysis and in a multivariate model. RESULTS: Nineteen patients (12.8%) died of bacteraemia. We found obesity (p = 0.002, RR 9.8; 95% CI 2.3 to 41.3), smoking (p < 0.001, RR 16.9; 95% CI 2.1 to 133.5), alcohol abuse (p = 0.008, RR 3.9; 95% CI 1.3 to 11.28), COPD (p = 0.01, RR 8.4; 95% CI 1.9 to 37.1) and rheumatoid arthritis (p = 0.045, RR 5.9; 95% CI 1.2 to 28.8) to be significantly associated with case fatality in bacteraemia in univariate model. The median BMI was significantly higher among those who died compared to survivors (33 vs. 26, p = 0.003). Obesity and smoking also remained independent risk factors for case fatality when their effect was studied together in a multivariate model adjusted with the effect of alcohol abuse, age (continuos variable), sex and causative organism. CONCLUSION: Our results indicate that obesity and smoking are prominent risk factors for case fatality in bacteraemic patients. Identification of risk factors underlying fatal outcome in bacteraemia may allow targeting of preventive efforts to individuals likely to derive greatest potential benefit

Tacrolimus versus Cyclosporine after Hematopoietic Cell Transplantation for Acquired Aplastic Anemia

AbstractCombinations of cyclosporine (CSP) with methotrexate (MTX) have been widely used for immunosuppression after allogeneic transplantation for acquired aplastic anemia. We compared outcomes with tacrolimus (TAC)+MTX versus CSP+MTX after transplantation from HLA-identical siblings (SIB) or unrelated donors (URD) in a retrospective cohort of 949 patients with severe aplastic anemia. Study endpoints included hematopoietic recovery, graft failure, acute graft-versus-host disease (GVHD), chronic GVHD, and mortality. TAC+MTX was used more frequently in older patients and, in recent years, in both SIB and URD groups. In multivariate analysis, TAC+MTX was associated with a lower risk of mortality in URD recipients and with slightly earlier absolute neutrophil count recovery in SIB recipients. Other outcomes did not differ statistically between the 2 regimens. No firm conclusions were reached regarding the relative merits of TAC+MTX versus CSP+MTX after hematopoietic cell transplantation for acquired aplastic anemia. Prospective studies would be needed to determine whether the use of TAC+MTX is associated with lower risk of mortality in URD recipients with acquired aplastic anemia

Pleural fluid soluble triggering receptor expressed on myeloid cells-1 as a marker of bacterial infection: a meta-analysis

<p>Abstract</p> <p>Background</p> <p>Pleural infection is a common clinical problem. Its successful treatment depends on rapid diagnosis and early initiation of antibiotics. The measurement of soluble triggering receptor expressed in myeloid cells-1 (sTREM-1) level in pleural effusions has proven to be a valuable diagnostic tool for differentiating bacterial effusions from effusions of other etiologies. Herein, we performed a meta-analysis to assess the accuracy of pleural fluid sTREM-1 in the diagnosis of bacterial infection.</p> <p>Methods</p> <p>We searched Web of Knowledge and Medline from 1990 through March 2011 for studies reporting diagnostic accuracy data regarding the use of sTREM-1 in the diagnosis of bacterial pleural effusions. Pooled sensitivity and specificity and summary measures of accuracy and Q* were calculated.</p> <p>Results</p> <p>Overall, the sensitivity of sTREM-1was 78% (95% CI: 72%-83%); the specificity was 84% (95% CI: 80%-87%); the positive likelihood ratio was 6.0 (95% CI: 3.3-10.7); and the negative likelihood ratio was 0.22 (95% CI: 0.12-0.40). The area under the SROC curve for sTREM-1 was 0.92. Statistical heterogeneity and inconsistency were found for sensitivity (p = 0.015, χ²= 15.73, I²= 61.9%), specificity (p = 0.000, χ²= 29.90, I²= 79.9%), positive likelihood ratio (p = 0.000, χ²= 33.09, I²= 81.9%), negative likelihood ratio (p = 0.008, χ²= 17.25, I²= 65.2%), and diagnostic odds ratio (p = 0.000, χ²= 28.49, I²= 78.9%). A meta-regression analysis performed showed that the Quality Assessment of Diagnostic Accuracy Studies score (p = 0.3245; RDOR, 4.34; 95% CI, 0.11 to 164.01), the Standards for Reporting of Diagnostic Accuracy score (p = 0.3331; RDOR, 1.70; 95% CI, 0.44 to 6.52), lack of blinding (p = 0.7439; RDOR, 0.60; 95% CI, 0.01 to 33.80), and whether the studies were prospective or retrospective studies (p = 0.2068; RDOR, 7.44; 95% CI, 0.18 to 301.17) did not affect the test accuracy. A funnel plot for publication bias suggested a remarkable trend of publication bias.</p> <p>Conclusions</p> <p>Our findings suggest that sTREM-1 has a good diagnostic accuracy and may provide a useful adjunctive tool for the diagnosis of bacterial pleural effusions. However, further studies are needed in order to identify any differences in the diagnostic performance of sTREM-1 of parapneumonic effusions and empyemas.</p

Comparative Analysis of Calcineurin Inhibitor-Based Methotrexate and Mycophenolate Mofetil-Containing Regimens for Prevention of Graft-versus-Host Disease after Reduced-Intensity Conditioning Allogeneic Transplantation

The combination of a calcineurin inhibitor (CNI) such as tacrolimus (TAC) or cyclosporine (CYSP) with methotrexate (MTX) or with mycophenolate mofetil (MMF) has been commonly used for graft-versus-host disease (GVHD) prophylaxis after reduced-intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (alloHCT), but there are limited data comparing efficacy of the 2 regimens. We evaluated 1564 adult patients who underwent RIC alloHCT for acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL), chronic myelogenous leukemia (CML), and myelodysplastic syndrome (MDS) from 2000 to 2013 using HLA-identical sibling (matched related donor [MRD]) or unrelated donor (URD) peripheral blood graft and received CYSP or TAC with MTX or MMF for GVHD prophylaxis. Primary outcomes of the study were acute and chronic GVHD and overall survival (OS). The study divided the patient population into 4 cohorts based on regimen: MMF-TAC, MMF-CYSP, MTX-TAC, and MTX-CYSP. In the URD group, MMF-CYSP was associated with increased risk of grade II to IV acute GVHD (relative risk [RR], 1.78; P <.001) and grade III to IV acute GVHD (RR, 1.93; P =.006) compared with MTX-TAC. In the URD group, use of MMF-TAC (versus MTX-TAC) lead to higher nonrelapse mortality. (hazard ratio, 1.48; P =.008). In either group, no there was no difference in chronic GVHD, disease-free survival, and OS among the GVHD prophylaxis regimens. For RIC alloHCT using MRD, there are no differences in outcomes based on GVHD prophylaxis. However, with URD RIC alloHCT, MMF-CYSP was inferior to MTX-based regimens for acute GVHD prevention, but all the regimens were equivalent in terms of chronic GVHD and OS. Prospective studies, targeting URD recipients are needed to confirm these results