bluuebunny/crossref_metadata_2025_split huggingface dataset:
563. Tocilizumab in the Treatment of Critical COVID-19 Pneumonia
Authors: Fisher Matthew , Marcos Luis , Monteforte Melinda , Taub Erin , Go Roderick 
Published: January 2021

Abstract

Background
The anti-interleukin-6 receptor monoclonal antibody tocilizumab has been proposed as a treatment for COVID-19 pneumonia although the efficacy remains unknown.

Methods
Patients with COVID-19 confirmed by nasal swab PCR for SARS-CoV-2 who were admitted to Stony Brook University Hospital in Suffolk County, New York between March 10th and April 2nd and received tocilizumab while undergoing mechanical ventilation in any intensive care unit were retrospectively analyzed from data available in the electronic medical record. Baseline characteristics and clinical outcomes were compared to mechanically ventilated patients admitted during the same time period who received standard hospital protocol.

Results
Forty-five patients received tocilizumab compared to seventy controls. Mean dose of tocilizumab given was 4.8mg/kg and mean time to receipt from initial intubation was 2.5 days. Baseline demographic characteristics, inflammatory markers, treatment with corticosteroids, and SOFA scores were similar between the two cohorts (Table 1). Patients who received tocilizumab had significantly lower Charlson co-morbidity index (2.0 versus 3.0, p = 0.01) and higher temperature (38.7 C versus 38.2 C, p = 0.004) than controls. There was no significant association between receipt of tocilizumab and the rate of extubation within fourteen days (44.4 percent versus 34.2 percent; OR = 1.53, 95% C.I. 0.71 – 3.30), discharge from hospital (51.1 percent versus 40.0 percent; OR = 1.568, 95% C.I. 0.737 – 3.337), or mortality (31.1 percent versus 41.4 percent; OR = 0.639, 95% C.I. 0.290 – 1.4407) (Table 2). Patients who were administered tocilizumab within two days of intubation had increased likelihood of extubation within fourteen days compared to those who were treated later (OR = 3.50, 95% C.I. 1.01 – 12.18). There was no observed increased risk of secondary infection in patients given tocilizumab (28.9 versus 25.7, OR = 1.1736, 95% C.I. = 0.507 – 2.714).
Table 1: Patient Demographics and Baseline Characteristics

Table 2: Primary Outcomes

Conclusion
Tocilizumab was not associated with a significant improvement in rate of extubation, hospital discharge, or reduction in mortality in this retrospective cohort study of mechanically ventilated patients with COVID-19 pneumonia. Further studies are needed to determine whether earlier treatment may result in improved outcomes.

Disclosures
All Authors: No reported disclosures
564. Tocilizumab Induces Rapid, Sustained Improvement of Inflammatory Markers in COVID-19
Authors: Colgrove Robert , Morin Scott , Jani Chinmay , Rupal Arashdeep , Bourque Daniel L 
Published: January 2021

Abstract

Background
Frequent observation of increasing fever and rising inflammatory markers late after onset of COVID-19 suggests Cytokine Release Syndrome (CRS, “Cytokine Storm”) may contribute to pathophysiology. Tocilizumab (TCZ), a monoclonal antibody targeting the receptor for the pro-inflammatory cytokine, IL-6, is effective in suppressing pathological inflammation in several rheumatological diseases. After administering TCZ to COVID-19 patients with suspected CRS, we observed a sharp fall in inflammatory indices. We analyzed this effect using results from the first 19 COVID-19 patients receiving TCZ at our hospital.

Methods
Data for all patients with confirmed COVID-19 who received TCZ at our center, a 200 bed community hospital in New England, were extracted from the Electronic Medical Record, including demographics, body temperature, C-Reactive Protein (CRP), IL-6 levels, clinical severity on the Ordinal Scale for Clinical Improvement (OSCI), and clinical outcome (recovery/discharge home, partial recovery/discharge rehab, death). Results were tabulated and statistical significance of changes in indices pre- and post- TCZ assessed by Wilcoxon Signed-Rank Test.

Results
19 patients received TCZ: 16 got 400mg x1, 2 got 400 mg x2, 1 got 660 mg x1. Median age was 64 years (range: 44–94), 68% male. Mean interval from symptom onset to receiving TCZ was 11.5 days. Mean IL-6 was 145 pg/mL. Demographics, OSCI scores, and discharge status are shown in Table 1. Average daily peak temperatures (Tmax) pre- and post- TCZ were 100.7 and 98.9°F, p&lt; 0.001. Mean CRP pre- and post- were 234 and 84.6 mg/L, p=0.001 (Fig.1). Decrease in Tmax and CRP was rapid and sustained (Fig. 2, 1st 8 patients shown for clarity.). 58% had improved clinical improvement by OSCI by day 7, 68% by day 14. 7 of 19 of patients were discharged home, 6 to rehab or acute care facility, and 6 died.
Table 1: Patient Demographics, Clinical Severity Score, and Discharge Status

Conclusion
In this cohort of patients with moderate-to-severe COVID-19 and evidence of Cytokine Release Syndrome, tocilizumab was associated with rapid resolution of fever and marked decline in CRP. Most patients showed improvement in clinical severity scores and no adverse reactions were noted. Tocilizumab may be useful in control of pathological inflammation in COVID-19. Controlled trials will be needed to assess overall clinical benefit.

Disclosures
All Authors: No reported disclosures
565. Tocilizumab Use in COVID-19: Act(emra) to Inhibit Intubation and Decompensation
Authors: Willner Debra M , Bengualid Victoria , Zada Ilanit , Berger Judith , Patel Nigam 
Published: January 2021

Abstract

Background
Tocilizumab is an IL-6 receptor inhibitor that has been utilized for the prevention and treatment of the cytokine storm inflammatory reaction in COVID-19. The objectives of this analysis were to evaluate clinical outcomes of tocilizumab treatment in relation to respiratory status improvements and to analyze the association between initial inflammatory markers and treatment outcomes.

Methods
IRB approved retrospective chart review of adult patients with confirmed COVID-19 treated with tocilizumab from March- May 2020. Data collection focused on relevant past medical history, hematologic and inflammatory markers before and after tocilizumab administration, concomitant COVID-19 treatments, and disease outcomes such as mortality and discharge. Assessed baseline characteristics and treatment outcomes in patients who received tocilizumab prior to intubation versus after intubation, and evaluated for any significant markers of treatment success and failure.

Results
84 patients were evaluated. Baseline characteristics did not vary between intubated and not intubated patients (Figure 1). Overall mortality in patients who received an IL-6 inhibitor was 43%. Mortality in patients who received IL-6 inhibitor when intubated (63%) compared to patients who were not intubated (26%) was significantly higher (p = 0.005). Patients with BMI’s of 30 or above and patients with diabetes had a higher rate of treatment failure (p &lt; 0.05) (Figure 2). Patients with IL-6 levels of 1000 or above had higher rates of treatment failure (p = 0.0001); however, given the small sample size larger studies are required for further analysis (Figure 3).
Baseline Characteristics by Respiratory Status Pre-Tocilizumab Administration

Subgroup Analysis

Outcome by Baseline IL-6 Levels

Conclusion
Overall mortality in our patients was 43%; however, our sample size was small and the study did not have a control group to fully assess treatment success or failure. Comorbidities such as diabetes and obesity, and elevated IL-6 levels were associated with significantly higher rates of treatment failure. Randomized control trials are needed to determine the true benefit of tocilizumab in COVID-19.

Disclosures
All Authors: No reported disclosures
567. Use of corticosteroids and COVID-19 mortality in patients with pneumonia in a tertiary care center in México City
Authors: Cabrera-Ruiz Maria L , Castillo-Álvarez José Luis , Barragán-Reyes Armando , Bay-Sansores Daniela , Pulido-Enríquez Jessica Isabel , Castañeda-Mendez Paulo F , Soto-Ramírez Luis Enrique 
Published: January 2021

Abstract

Background
The use of corticosteroids, specifically dexamethasone has been associated to low mortality in COVID-19 patients. We present here the mortality related to the use of corticosteroids in the first two months of the SARS-CoV-2 outbreak in México City.

Methods
We conducted a case series of patients with the diagnosis of pneumonia due to SARS-CoV-2 virus admitted to a tertiary care center in Mexico City, between March 14th and May 14th, 2020. Data collected included demographic information, comorbidities, treatment and outcomes including mortality.

Results
We included 109 patients with diagnosis of COVID-19 associated pneumonia with computed tomography; 76(69.7%) were male and 33(30.3%) female with a median age of 52 yo (24–85) and 51 yo (25–81), respectively. Most common comorbidities were overweight (48.6%), obesity (35.8%), hypertension (23.8%), and diabetes (18.3%). Thirty-eight patients received corticosteroids (Methylprednisolone 30, Hydrocortisone 6 and dexamethasone and prednisone in on case). Mortality in those that used corticosteroids was 21% (8/38) and 5.6% for those that did not received (4/71), p=0.014.
Forty cases needed mechanical ventilation from the beginning, and 24 of those received corticosteroids with a mortality of 29% (7/24), while the mortality was 18.7% (3/16) in those with no steroid use, p=0.45.

Conclusion
Mortality in our small cohort with predominantly use of methylprednisolone is not lower in those using steroids. In fact, mortality was significantly higher in those that received corticosteroids, while this significance was not maintained in those that needed immediate mechanical ventilation. Use of corticosteroids for COVID-19 patients with pneumonia, should be further investigated.

Disclosures
All Authors: No reported disclosures
574. De-escalation of Broad Spectrum Antibiotics during Cytokine Release Syndrome with Haploidentical Hematopoietic Stem Cell Transplantation
Authors: Schiffer Molly , Perreault Sarah , McManus Dayna , Foss Francine , Gowda Lohith , Isufi Iris , Seropian Stuart , Topal Jeffrey E 
Published: January 2021

Abstract

Background
Fever is a common component of cytokine release syndrome (CRS) occurring in 90% of patients undergoing haploidentical hematopoietic stem cell transplantation (Haplo-HSCT). Fevers typically occur between the stem cell infusion (Day 0) and initiation of post-transplant cyclophosphamide and are often confused with febrile neutropenia (FN). Due to longer time to engraftment in Haplo-HSCT, CRS/FN exposes patients to prolonged courses of empiric broad spectrum antibiotic (BSA) therapy increasing the risk for multi-drug resistant organisms. Recently, at Yale New Haven Health, our practice has changed to now recommend antibiotic de-escalation to prophylaxis after 7 days of BSA if no infection is identified. The objective of this study was to assess the incidence of breakthrough infections with the de-escalation of BSA in CRS/FN. Secondary endpoints include rate of FN, rate of de-escalation, rate of recurrent fevers, duration of BSA, and positive blood culture data.

Methods
The patient population included those undergoing Haplo-HSCT between July 2016 and February 2020 and who developed CRS/FN between Day 0 and Day +5. Patients were excluded if they had prolonged hospitalization due to non-infectious complications or engraftment failure. Bacteremia was defined using NHSN definitions.

Results
Of the 53 Haplo-HSCTs assessed, 43 experienced CRS/FN. Thirty-five Haplo-HSCT (81%) with CRS/FN had negative cultures and 23 (66%) of these were de-escalated back to antibacterial prophylaxis. The median duration of BSA in the de-escalated group was 7 days (range 5–13) compared to 16.5 days range (13–21) in the non-de-escalated group (p&lt; 0.001). Among those de-escalated, 7 (30%) had recurrent fever occurring at a median of 4 days (range 2–14) and were placed back on BSA. Two Haplo-HSCT (9%) that had fever after de-escalation developed a breakthrough bacteremia. No Haplo-HSCT after de-escalation had fever or re-admission for bacteremia 30 days after engraftment. Four Haplo-HSCT (9%) with CRS/FN had positive blood cultures; however, three (7%) were still able to be de-escalated from BSA to narrower agents based on susceptibilities.

Conclusion
De-escalation of BSA in FN/CRS in Haplo-HSCT patients reduced unnecessary, prolonged antibiotic exposure with a low incidence of breakthrough infections.

Disclosures
All Authors: No reported disclosures
576. Half-dose Valganciclovir Prophylaxis is Safe and Cost-effective in CMV Seropositive Renal Transplant Recipients
Authors: shi yiyun , Rogers Ralph , Vieira Kendra , Merhi Basma , Osband Adena , Bayliss George , Gohh Reginald , Morrissey Paul , Farmakiotis Dimitrios 
Published: January 2021

Abstract

Background
Observational studies suggest that half-dose valganciclovir (VGV) prophylaxis (450 mg daily for normal renal function) is as effective as full-dose (900 mg daily) in preventing CMV infection among kidney transplant recipients (KTR). However, this practice is not supported by current guidelines, for fear of selecting resistance, mainly in high-risk, i.e. donor CMV seropositive/recipient negative (D+/R-) KTR. Full-dose VGV is costly, and possibly associated with higher incidence of neutropenia and BK viremia. Our institution adopted half-dose VGV prophylaxis for R+ KTR in January 2018.

Methods
We included R+ KTR transplanted between 1/1/2014 and 12/31/2018 at our center. Data were censored at 1-year post-transplant, graft loss or death. Primary outcomes were early (&lt; 6 months from transplant) and any CMV viremia. Secondary outcomes were neutropenia, BK viremia, graft loss and death. Categorical variables were compared with χ 2 or Fisher’s exact tests, continuous variables with the Mann-Whitney test. We used log-rank and Gray’s tests to compare cumulative incidence of outcomes, after adjustment by propensity score for differences in baseline characteristics.

Results
106 R+ KTR received full-dose and 35 half-dose VGV. Antithymocyte globulin (ATG) induction was associated with significantly higher cumulative incidence of both early (P=0.017) and any (P=0.02) CMV viremia, compared to basiliximab induction (Fig. 1). After adjusting for gender and induction regimen, we noted a signal for higher cumulative incidence of any (P=0.044), but not early (P=0.598) CMV viremia in the full-dose VGV group (Fig. 2). There were no significant differences (P &gt;0.1) in incidence of neutropenia, BK viremia, graft loss or death between the two groups. Cost savings were estimated at $2630 per CMV R+ KTR (Table 1).
Table 1. Comparison of outcomes and cost between the two anti-CMV prophylaxis groups. Data are presented as n (%), unless otherwise indicated.

Fig 1. Probability of CMV viremia in KTR who received ATG vs. basiliximab induction.

Fig 2. Probability of CMV viremia in KTR who received full-dose vs. half-dose VGV prophylaxis.

Conclusion
In our pilot series, half-dose VGV was at least as effective as full-dose VGV in preventing CMV viremia in R+ RTR, and less costly. If larger scale studies verify generalizability of these results, half-dose VGV may be considered as standard of care for R+ KTR. In KTR, the antimetabolite probably contributes to neutropenia more than VGV prophylaxis.

Disclosures
All Authors: No reported disclosures
578. Infections in Patients Treated with Chimeric Antigen Receptor T-cells (CAR-T) therapy
Authors: Tran Nikki , Eschenauer Gregory , Scappaticci Gianni , Frame David , Miceli Marisa H , Patel Twisha S 
Published: January 2021

Abstract

Background
Although chimeric antigen receptor T cells (CAR-T) is a promising novel therapy for the treatment of relapsed or refractory (R/R) B-cell malignancies, data on infectious complications associated with this therapy are limited. Therefore, further assessment of infections after CAR-T therapy is warranted.

Methods
We retrospectively reviewed and analyzed infectious complications for 6 months following CAR-T therapy infusion (CTI) in 39 adult and pediatric patients with R/R acute lymphoblastic leukemia (ALL) and Non-Hodgkin Lymphoma (NHL) at Michigan Medicine.

Results
Overall, 20 infections were identified in 16 of 39 patients (41%) following CTI [detailed in Table 1]; 8 (40%) infections occurred in the early period (Day 0–30) and 12 (60%) infections occurred during late period (Day 31–180). The most common infections were viral (n=10, 50%; 80% of viral infections were respiratory viruses), followed by 8 bacterial infections (40%), and 2 fungal infections (10%). More bacterial infections were seen in the early period post-CTI (30% vs. 10%, p = 0.019), whereas viral infections were more common during the late period (40% vs. 10%, p = 0.68). Antimicrobial prophylaxis prior to CTI and following CTI were similar (Table 2). The majority of patients included in the study had NHL (n=32, 82%). Mean age of the cohort was 52 ± 22 years, and 64% were male. 85% of the population developed cytokine release syndrome (CRS) with 67% grade 1–2 and 18% grade 3–5. As shown in Table 2, most baseline characteristics were similar between patients with and without infections post CTI except infected patients were older (63.3 ± 11.3 vs. 44.8 ± 24.2, p = 0.01) and more received steroids for CRS (56% vs 17%, p = 0.02). All-cause mortality within 6 months following CTI was similar in infected and uninfected groups (38% vs 26%, p= 0.50).
Table 1

Table 2

Conclusion
Infectious complications are common following CAR-T therapy. We found the majority of infections to be caused by various bacteria or respiratory viruses in a cohort of patients with lymphoma as the most common underlying malignancy.

Disclosures
Marisa H. Miceli, MD, FIDSA, SCYNEXIS, Inc. (Advisor or Review Panel member)
579. Prophylactic Antibiotics Did Not Decrease Recurrent Cholangitis in Patients with Biliary Atresia After Kasai Portoenterostomy
Authors: Tarro Thomas M , Song Laurie , Carter Beth A , Yeh Meiyu , Pannaraj Pia S , Mohandas Sindhu 
Published: January 2021

Abstract

Background
Biliary atresia (BA) is a rare, progressive, idiopathic, fibro-obliterative disease of the extrahepatic biliary tree seen in children. The current standard treatment is surgical management with Kasai portoenterostomy (KP). Bacterial cholangitis is a frequent complication following KP and an important determinant of long-term prognosis. Use of prophylactic antibiotics is common but not universal and efficacy is controversial.

Methods
A retrospective study was performed that included all patients with BA who underwent KP from November 2002 to July 2019. Chart review was conducted to collect demographic information and evaluate the use of antibiotic prophylaxis, number of cholangitis episodes, time to liver transplantation (LVT), and survival.

Results
Ninety-one patients with BA underwent KP during the study period. Seventy-two (79%) received prophylactic antibiotics, and 19 (21%) did not. The median duration of prophylactic antibiotics was 7 months (interquartile range [IQR] 8.5). Patients in the no-prophylaxis group had significantly fewer cholangitis episodes (median 0, IQR 1) than in the antibiotic prophylaxis group (median 1, IQR 2), p= 0.0201. The median time to LVT was 8 months (IQR 8.5) in the antibiotic prophylaxis group, compared to 7 months (IQR 6) in the no-prophylaxis group, p=0.8827. Of the patients who were on antibiotic prophylaxis, 57 (79.2%) received trimethoprim-sulfamethoxazole (TMP-SMX) alone and 15 (20.8%) received multiple/other antibiotics. Seven patients (7.7%) had culture-positive cholangitis. Six of 7 received prophylaxis with TMP-SMX and 5 of 7 grew bacteria that were resistant to TMP-SMX. No deaths occurred between the postoperative KP period to the time of LVT in both groups.
Table 1. Characteristics of Patients in the Prophylaxis and No-prophylaxis Groups.

Table 2. Impact of Prophylactic Antibiotics in the Period Between Kasai Portoenterostomy and Liver Transplantation.

Table 3. Patients with Culture-positive Cholangitis after Kasai Portoenterostomy (n=7).

Conclusion
Antibiotic prophylaxis was frequently used after KP with TMP-SMX being the most common antibiotic used. Patients in the no-prophylaxis group had significantly fewer cholangitis episodes compared to those receiving antibiotic prophylaxis. Prophylactic antibiotics did not have an impact on time to LVT. Our findings suggest that antibiotic prophylaxis is not helpful in decreasing the frequency of cholangitis episodes after KP and may increase the risk for infections with resistant bacteria. Larger prospective randomized control studies are recommended.

Disclosures
Pia S. Pannaraj, MD, MPH, AstraZeneca (Grant/Research Support)Pfizer (Grant/Research Support)Sanofi Pasteur (Advisor or Review Panel member)
580. Refractory and Resistant CMV Infections in Hematopoietic Cell Transplant Recipients in the Letermovir Primary Prophylaxis Era
Authors: Sassine Joseph , Khawaja Fareed , Handy Victoria , Shigle Terri Lynn , Foolad Farnaz , Aitken Samuel L , Aitken Samuel L , Heredia Ella Ariza , Chemaly Roy F 
Published: January 2021

Abstract

Background
CMV reactivation is one of the most common infections after allogeneic hematopoietic cell transplantation (allo-HCT) and carries considerable morbidity and mortality. Primary prophylaxis with letermovir demonstrated in clinical trials reduction of the incidence of clinically significant CMV infection (CS-CMVi). This study aims at exploring the effect of letermovir primary prophylaxis on the occurrence of refractory or resistant CMV infections.

Methods
This is a single-center, retrospective cohort study of 537 consecutive allo-HCT CMV-seropositive recipients cared for between March 2016 and December 2018. Baseline demographics, transplant characteristics, CMV infections, treatment and mortality data were collected from the electronic medical record (Table 1). CMV outcomes were defined according to the standardized definitions for clinical trials. Data was analyzed on IBM® SPSS version 24 using a logistic regression model for multivariate analysis.

Results
Out of 537 patients identified, 123 received letermovir for primary prophylaxis during the first 100 days post-HCT and 414 did not. In a multivariate analysis, primary prophylaxis with letermovir was associated with a reduction in CS-CMVi (OR 0.11, 95% CI 0.06–0.20), CMV disease (OR 0.20, 95% CI 0.08–0.46) and refractory or resistant CMV infection (OR 0.11, 95% CI 0.02–0.49) (Table 2). Notably, there was no resistant CMV and no CMV-related mortality in the letermovir group. There was a trend towards lower all-cause mortality at day 100 in the letermovir group (OR 0.48, 95% CI 0.18–1.2).
Table 1 - Baseline Characteristics.

Table 2 - Multivariate Analysis of Clinical Outcomes.

Conclusion
Our study showed a strong association between primary prophylaxis with letermovir and reduction in refractory or resistant CMV infections and CMV disease in allo-HCT recipients.

Disclosures
Ella Ariza Heredia, MD, Merck Sharp & Dohme (Grant/Research Support)Oxford Immunotec (Grant/Research Support) Roy F. Chemaly, MD, MPH, FACP, FIDSA, Chimerix (Consultant, Research Grant or Support)Clinigen (Consultant)Merck (Consultant, Research Grant or Support)Novartis (Research Grant or Support)Oxford Immunotec (Consultant, Research Grant or Support)Shire/Takeda (Research Grant or Support)Viracor (Research Grant or Support)