O-020 Aneuploidy and mosaicism in human embryos: How correct detection may improve IVF clinical outcomes

Abstract text Study question Can new next-generation sequencing (NGS) based strategies for preimplantation genetic testing of aneuploidy (PGT-A) improve clinical outcomes after assisted reproductive technology (ART)? Summary answer Recent randomised controlled trials (RCTs) suggest that NGS-based PGT-A strategies can improve clinical outcomes for older women. The clinical management of mosaic embryos remains controversial. What is known already There are two types of chromosome abnormalities present in embryos, meiotic arising mostly during oogenesis, and mitotic arising after fertilisation. Meiotic aneuploidies are present in all of the embryonic cells and in their vast majority are lethal. Conversely, mitotic abnormalities are present in only part of the embryonic cells with the remaining cells having a different cytogenetic constitution. This phenomenon is known as mosaicism. The sensitivity of NGS meant that mosaic aneuploidy became readily detectable in trophectoderm (TE) samples during PGT-A. The viability and clinical management of mosaic embryos has led to debates and controversies in the reproductive medicine field. Study design, size, duration The study involved an assessment of the impact of mosaic chromosome abnormalities to embryonic viability and clinical outcomes after ART cycles using PGT-A via NGS. A large number of embryos generated in IVF clinics in Europe and the USA was examined. Participants/materials, setting, methods Embryos were generated by couples referred for PGT-A due to various indications. All embryos were cultured to the blastocyst stage, and underwent a TE biopsy, followed by vitrification. TE samples were shipped to 6 reference PGT laboratories and analysed via the use of the same NGS platform. Mosaic chromosome abnormalities were scored according to validated thresholds set by the reference laboratories. The clinical management of mosaic embryos took place according to published guidelines. Main results and the role of chance Comparison of clinical outcomes seen after the transfer of mosaic embryos with those seen after the transfer of euploid embryos led to the following findings: Mosaic embryos with <40% abnormal cells in the TE sample had an OIR of 50% compared to 27% for mosaics with 40–80% abnormal cells in the TE, and 9% for complex mosaic embryos. Karyotyping of ongoing pregnancies resulting after the transfer of mosaic embryos demonstrated a normal chromosome constitution of the resulting foetuses. Limitations, reasons for caution - Cytogenetic classification was based on TE samples removed from blastocysts during PGT-A analysis. As only a fraction of the cells from each embryo are tested, inevitably some mosaic embryos will be incorrectly classified fully euploid or aneuploid. However, this misclassification is expected to have little impact on the results. Wider implications of the findings - The transfer of NGS-classified mosaic embryos was associated with poorer clinical outcomes compared to euploid embryos. However, the ongoing pregnancies resulting from mosaic transfers were euploid. NGS’s ability to identify embryos of reduced viability has the potential to improve IVF clinical outcomes.

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Preimplantation Genetic Testing for Chromosomal Abnormalities: Aneuploidy, Mosaicism, and Structural Rearrangements

Genes ◽

10.3390/genes11060602 ◽

2020 ◽

Vol 11 (6) ◽

pp. 602 ◽

Cited By ~ 5

Author(s):

Manuel Viotti

Keyword(s):

Genetic Testing ◽

Clinical Outcomes ◽

Assisted Reproductive Technologies ◽

Chromosomal Abnormalities ◽

Reproductive Technologies ◽

Chromosomal Mosaicism ◽

Human Embryos ◽

Chromosomal Anomalies ◽

Structural Rearrangements ◽

Preimplantation Genetic Testing

There is a high incidence of chromosomal abnormalities in early human embryos, whether they are generated by natural conception or by assisted reproductive technologies (ART). Cells with chromosomal copy number deviations or chromosome structural rearrangements can compromise the viability of embryos; much of the naturally low human fecundity as well as low success rates of ART can be ascribed to these cytogenetic defects. Chromosomal anomalies are also responsible for a large proportion of miscarriages and congenital disorders. There is therefore tremendous value in methods that identify embryos containing chromosomal abnormalities before intrauterine transfer to a patient being treated for infertility—the goal being the exclusion of affected embryos in order to improve clinical outcomes. This is the rationale behind preimplantation genetic testing for aneuploidy (PGT-A) and structural rearrangements (-SR). Contemporary methods are capable of much more than detecting whole chromosome abnormalities (e.g., monosomy/trisomy). Technical enhancements and increased resolution and sensitivity permit the identification of chromosomal mosaicism (embryos containing a mix of normal and abnormal cells), as well as the detection of sub-chromosomal abnormalities such as segmental deletions and duplications. Earlier approaches to screening for chromosomal abnormalities yielded a binary result of normal versus abnormal, but the new refinements in the system call for new categories, each with specific clinical outcomes and nuances for clinical management. This review intends to give an overview of PGT-A and -SR, emphasizing recent advances and areas of active development.

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O-085 In-depth analysis of embryo development: Differences among monosomic, trisomic and chromosomally chaotic embryos compared to euploid embryos

Human Reproduction ◽

10.1093/humrep/deab125.015 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

F Meseguer Estornell ◽

L Bori ◽

R Maor ◽

I Kottel ◽

D Gilboa ◽

...

Keyword(s):

Embryo Development ◽

Chromosomal Abnormalities ◽

Chromosome Abnormality ◽

Automated System ◽

Human Embryos ◽

Developmental Milestones ◽

Preimplantation Genetic Testing ◽

Depth Analysis ◽

The Impact

Abstract Study question Is there any visible variation in the development of aneuploid embryos depending on the type of chromosome abnormality? Summary answer There were significant visible differences in the development of euploid, monosomic, trisomic and, especially, chaotic embryos. What is known already Aneuploidy rates are remarkably high in in vitro fertilized human embryos, with up to 50% of embryos diagnosed as aneuploid based on preimplantation genetic testing for aneuploidies (PGT-A). However, very little is known about the impact of specific aneuploidies during the early human embryo development. A recent publication showed that embryos with single chromosomal gain or loss reached the blastocyst stage later or earlier depending on the chromosome affected (Shahbazi et al., 2020). In our study, we wanted to detect observable differences in embryo behavior between embryos with different chromosomal abnormalities during the entire in vitro development. Study design, size, duration This was a retrospective study including 2,500 blastocysts with PGT-A results. Embryos were cultured in EmbryoScope systems until the fifth/sixth day of development (up to the time of trophectoderm biopsy). Automatic-annotations for division times and quality gradings were supervised routinely by senior embryologists using Guided Annotations Tool. Out of the total, 1,000 were euploid embryos used for reference and 1,500 were aneuploid embryos with one or more defects, including monosomic, trisomic and chromosomally chaotic embryos. Participants/materials, setting, methods Chromosome analysis was performed using next-generation sequence technology. Then, an in-depth analysis of time-lapse videos and supervised-automatic annotations was performed. We calculated the proportion of embryos, in each aneuploid category, that reached one specific event later than the expected value for euploid embryos plus one standard deviation. Later, we calculated the “relative risk” of an embryo of reaching the milestone late. We did the same for the time between milestones and for pairs of milestones. Main results and the role of chance Every aneuploid category was more likely to reach each specific embryo developmental event later than euploid embryos and the time gaps between developmental milestones were also statistically longer in aneuploid embryos (p < 0.0001). The following results were the most interesting relative risks (RR) when we compared the proportion of embryos (in each aneuploid category) to the proportion of euploid embryos (RR for euploid = 1). For reaching the division time to two cells (t2): 1.31 in monosomic embryos, 1.50 in trisomic embryos and 2.43 in chaotic embryos. For the division time to four cells (t4): 1.42 in monosomic embryos, 1.54 in trisomic embryos and 3.07 in chaotic embryos. For the division time to eight cells (t8) and the time of starting blastulation: 1.45 in monosomic embryos, 1.22 in trisomic embryos and 2.74 in chaotic embryos. Combined milestones were stronger indicators than each milestone by itself, the RR were: 1.63 in monosomic embryos, 1.81 in trisomic embryos and 3.35 in chaotic embryos for t2 and t4; 1.50 in monosomic embryos, 1.80 in trisomic embryos and 2.84 in chaotic embryos for t2 and t8; 1.46 in monosomic embryos, 1.90 in trisomic embryos and 3.43 in chaotic embryos for t4 and t8. Limitations, reasons for caution At this stage, we did not go down to specific chromosome abnormality as there were very few cases in each fully detailed category. Also, not all the embryos reached every developmental milestone. Wider implications of the findings Aneuploid embryos were significantly different from euploid embryos in the first five days of development. A large proportion of aneuploid embryos could be rejected because their developmental milestones falling outside the normal range. This could form part of an automated system for determining euploidy/aneuploidy from observation of embryos in vitro. Trial registration number 1902-VLC-018-MM

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PREIMPLANTATION GENETIC TESTING: Chromosome abnormalities in human embryos

Reproduction ◽

10.1530/rep-20-0022 ◽

2020 ◽

Vol 160 (5) ◽

pp. A33-A44

Author(s):

Carmen Rubio ◽

Lorena Rodrigo ◽

Carlos Simón

Keyword(s):

Genetic Testing ◽

Culture Media ◽

Sperm Concentration ◽

Early Embryo ◽

Chromosome Abnormalities ◽

Critical Event ◽

Human Embryos ◽

Preimplantation Genetic Testing ◽

Frequent Event

Aneuploidy is a frequent event in human embryos, and its incidence is higher in oocytes and embryos from women of advanced maternal age. Aneuploidy may also be a contributing factor in infertile populations, such as couples with recurrent miscarriages, repetitive implantation failure, or male infertility. For these reasons, preimplantation genetic testing for aneuploidy (PGT-A) has been proposed to prevent miscarriages and increase live birth rates in infertile couples undergoing in vitro fertilisation. Next-generation sequencing is currently being applied for the detection of aneuploidies in human embryos, including whole chromosome aneuploidies, segmental aneuploidies, uniform, and mosaic aneuploidies. More recently, this technology has been incorporated for the analysis of the cell-free DNA secreted by the embryo to the culture media. Chromosome abnormalities mostly originate in female meiosis. Recombination between homologous chromosomes is a critical event that occurs in the foetal ovary. The importance of altered recombination pertains to paternally as well as maternally derived trisomies, but as most aneuploidy arises during oogenesis, the female is at greater risk. For males, sperm concentration is associated with a higher risk of aneuploid sperm and thus aneuploid embryos. Mitosis errors can occur at all stages of early embryo development that result in chromosomally distinct cell populations. The clinical impact of mosaicism depends on the mosaicism type, location, and number of aneuploid cells. Transfer of mosaic embryos has been proposed when no euploid embryos are available in the PGT-A cycle.

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Culture of human embryos for studies on the derivation of human pluripotent cells: a preliminary investigation

Reproduction Fertility and Development ◽

10.1071/rd98083 ◽

1998 ◽

Vol 10 (8) ◽

pp. 557 ◽

Cited By ~ 4

Author(s):

M-C. Lavoir ◽

J. Conaghan ◽

R. A. Pedersen

Keyword(s):

High Efficiency ◽

Preliminary Investigation ◽

Embryonic Stem ◽

Blastocyst Stage ◽

Culture Conditions ◽

Human Embryos ◽

Heparin Binding ◽

Embryonic Cells ◽

Epidermal Growth ◽

Serum Substitute

Several different culture conditions were evaluated for culturing grade 4embryos (containing 2–4 blastomeres and with >50%fragmentation) 68 h after fertilization to the blastocyst stage. Embryos wereco-cultured with buffalo rat liver (BRL) cells in Menezo's B2 medium withor without 10% v/v synthetic serum substitute (SSS), co-culturedwith BRL cells in KSOM with or without 10% SSS, or cultured in KSOMwith 100 nM heparin binding epidermal growth factor. The most consistentdevelopment was obtained when embryos were co-cultured with BRL cells in KSOM.Rates of development to the blastocyst stage were between 27% and40%. After reaching the blastocyst stage, continued culture of theseblastocysts was only possible in a medium without serum. In a serum-deprivedmedium cells attached and showed initial outgrowth, but did not survivepassaging. Using another approach, inner cell masses (ICMs), isolated fromblastocysts with high efficiency using immunosurgery, were able to attach to afeeder layer in the presence of serum. Some ICMs differentiated whereas otherscould be succesfully passaged up to four times. The embryonic cells were morphologically different from murine embryonic stem cells. Instead ofwell-defined colonies, the human colonies were characterized by individualcells and colonies without defined borders.

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The Learning Curve in Arthroscopic ACL Reconstruction. The impact on the Surgical Time and Postoperative Clinical Results

Revista de Chimie ◽

10.37358/rc.18.10.6643 ◽

2018 ◽

Vol 69 (10) ◽

pp. 2874-2876

Author(s):

Teodor Negru ◽

Stefan Mogos ◽

Ioan Cristian Stoica

Keyword(s):

Anterior Cruciate Ligament ◽

Learning Curve ◽

Clinical Outcomes ◽

Positive Impact ◽

Cruciate Ligament ◽

Clinical Results ◽

Single Bundle ◽

Surgical Time ◽

Anterior Cruciate ◽

The Impact

Rupture of the anterior cruciate ligament (ACL) is a common injury. The objective of the current study was to evaluate if the learning curve has an impact on surgical time and postoperative clinical outcomes after anatomic single-bundle anterior cruciate ligament reconstruction (ACLR) using an outside-in tunnel drilling hamstrings technique. The learning curve has a positive impact on surgical time but has no influence on postoperative clinical outcomes at short time follow-up.

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Projecting the long-term benefits of single pill combination therapy for patients with hypertension in five countries

European Heart Journal ◽

10.1093/ehjci/ehaa946.2781 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

C Borghi ◽

J.G Wang ◽

A.V Rodionov ◽

M Rosas ◽

I.S Sohn ◽

...

Keyword(s):

Combination Therapy ◽

South Korea ◽

Health Outcomes ◽

Clinical Outcomes ◽

Funding Source ◽

Combination Therapies ◽

Private Company ◽

Treatment Pathways ◽

Single Pill ◽

The Impact

Abstract Background It is well established that single pill combination (SPC) therapies have the potential to improve patient adherence versus multi-pill regimens, thereby improving blood pressure control and clinical outcomes in populations with hypertension. Purpose To develop a microsimulation model, capturing different treatment pathways, to project the impact on clinical outcomes of using single pill combination therapies for the management of hypertension in five countries (Italy, Russia, China, South Korea and Mexico). Methods The model was designed to project health outcomes between 2020 and 2030 for populations with hypertension managed according to four different treatment pathways: current treatment practices [CTP], single drug with dosage titration first then sequential addition of other agents [start low and go slow, SLGS], free choice combination with multiple pills [FCC] and combination therapy in the form of a single pill [SPC]. Model inputs were derived from Global Burden of Disease 2017 dataset, including demographics, health status/risk factors, transition probabilities and treatment attributes/healthcare utilization, and the model incorporated real-world challenges to healthcare delivery such as access to care, SBP measurement error, adherence and therapeutic inertia. Simulated outcomes of mortality, incidence of chronic kidney disease (CKD), stroke and ischemic heart disease (IHD), and disability-adjusted life years (DALYs) due to these conditions were estimated for population of 1,000,000 simulated patients for each treatment pathway and country. Results SPC therapy was projected to improve health outcomes over SLGS, FCC and CTP over 10 years in all five countries. SPC was forecast to reduce mortality by 5.4% (Italy), 4.9% (Russia), 4.5% (China), 2.3% (South Korea) and 3.6% (Mexico) versus CTP and showed greater projected reductions in mortality than SLGS and FCC. DALYs were projected to be reduced with SPC therapy by between 5.7% (Italy) and 2.2% (South Korea) compared with CTP and reductions in the incidence of clinical events were also projected with SPC therapy, with decreases in the range of 11.5% (Italy) to 4.9% (South Korea) versus CTP. Conclusions Ten-year projections of clinical outcomes associated with different anti-hypertensive treatment pathways in five countries indicated that both combination therapies (FCC and SPC) are likely to reduce the disease burden of hypertension compared with conventional management approaches, with SPC showing the greatest overall benefits due to improved adherence. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Sanofi, Gentilly, France

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288. Follow-Up Blood Cultures in Gram-Negative Bacteremia: How Do They Impact Outcomes

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.331 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S144-S144

Author(s):

Azza Elamin ◽

Faisal Khan ◽

Ali Abunayla ◽

Rajasekhar Jagarlamudi ◽

aditee Dash

Keyword(s):

Clinical Outcomes ◽

Antibiotic Treatment ◽

Readmission Rate ◽

Blood Cultures ◽

Categorical Variables ◽

Gram Negative ◽

Number Of Patients ◽

Significant Difference ◽

The Impact

Abstract Background As opposed to Staphylococcus. aureus bacteremia, there are no guidelines to recommend repeating blood cultures in Gram-negative bacilli bacteremia (GNB). Several studies have questioned the utility of follow-up blood cultures (FUBCs) in GNB, but the impact of this practice on clinical outcomes is not fully understood. Our aim was to study the practice of obtaining FUBCs in GNB at our institution and to assess it’s impact on clinical outcomes. Methods We conducted a retrospective, single-center study of adult patients, ≥ 18 years of age admitted with GNB between January 2017 and December 2018. We aimed to compare clinical outcomes in those with and without FUBCs. Data collected included demographics, comorbidities, presumed source of bacteremia and need for intensive care unit (ICU) admission. Presence of fever, hypotension /shock and white blood cell (WBC) count on the day of FUBC was recorded. The primary objective was to compare 30-day mortality between the two groups. Secondary objectives were to compare differences in 30-day readmission rate, hospital length of stay (LOS) and duration of antibiotic treatment. Mean and standard deviation were used for continuous variables, frequency and proportion were used for categorical variables. P-value < 0.05 was defined as statistically significant. Results 482 patients were included, and of these, 321 (67%) had FUBCs. 96% of FUBCs were negative and 2.8% had persistent bacteremia. There was no significant difference in 30-day mortality between those with and without FUBCs (2.9% and 2.7% respectively), or in 30-day readmission rate (21.4% and 23.4% respectively). In patients with FUBCs compared to those without FUBCs, hospital LOS was longer (7 days vs 5 days, P < 0.001), and mean duration of antibiotic treatment was longer (14 days vs 11 days, P < 0.001). A higher number of patients with FUBCs needed ICU care compared to those without FUBCs (41.4% and 25.5% respectively, P < 0.001) Microbiology of index blood culture in those with and without FUBCs Outcomes in those with and without FUBCs FUBCs characteristics Conclusion Obtaining FUBCs in GNB had no impact on 30-day mortality or 30-day readmission rate. It was associated with longer LOS and antibiotic duration. Our findings suggest that FUBCs in GNB are low yield and may not be recommended in all patients. Prospective studies are needed to further examine the utility of this practice in GNB. Disclosures All Authors: No reported disclosures

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Effect of Obesity on Clinical Failure of Patients Treated with Beta-Lactams

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab212 ◽

2021 ◽

Author(s):

Nathan A Pinner ◽

Natalie G Tapley ◽

Katie E Barber ◽

Kayla R Stover ◽

Jamie L Wagner

Keyword(s):

Treatment Failure ◽

Clinical Outcomes ◽

Hospital Length Of Stay ◽

Source Control ◽

Definitive Treatment ◽

Therapeutic Drug ◽

Obese Patients ◽

Definitive Therapy ◽

All Cause Mortality ◽

The Impact

Abstract Background Altered pharmacokinetics in obese patients raise concerns over worse clinical outcomes. This study assessed whether obese patients receiving a beta-lactam (BL) have worse clinical outcomes compared to non-obese patients and to identify if therapeutic drug monitoring (TDM) may be beneficial. Methods This multi-center, retrospective cohort included hospitalized adults admitted from July 2015-July 2017 treated with a BL as definitive monotherapy against a Gram-negative bacilli for ≥72 hours. Patients were excluded if there was lack of source control or if polymicrobial infections required >1 antibiotic for definitive therapy. Patients were classified based on body mass index (BMI): non-obese (BMI ≤29.9 kg/m 2) and obese (BMI ≥30.0 kg/m 2). The primary outcome was clinical treatment failure, and secondary were hospital length of stay (LOS), inpatient all-cause mortality, and 30-day all-cause readmission. Results There were 257 (43.6%) obese patients and 332 (56.4%) non-obese patients included. The most common infections were urinary (50.9%) and respiratory (31.4%). Definitive treatment was driven by 3 rd generation cephalosporins (46.9%) and cefepime (44.7%). Treatment failure occurred in 131 (51%) obese patients and 109 (32.8%) non-obese patients (p<0.001). Obesity and respiratory source were independently associated with increased likelihood of treatment failure. Obese patients were hospitalized longer than non-obese patients (p=0.002), but no differences were found for all-cause mortality (p=0.117) or infection-related readmission (0=0.112). Conclusions Obese patients treated with BLs have higher rates of treatment failure and longer hospitalization periods than non-obese patients. Future studies are needed to assess the impact of TDM and specific dosing recommendations for targeted infection types.

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Evaluating clinical outcomes of routinely delivered task-shared care for depression in rural Haiti

Global Mental Health ◽

10.1017/gmh.2021.17 ◽

2021 ◽

Vol 8 ◽

Author(s):

Alexandra L. Rose ◽

Ryan McBain ◽

Jesse Wilson ◽

Sarah F. Coleman ◽

Emmanuel Mathieu ◽

...

Keyword(s):

Mental Health ◽

Clinical Outcomes ◽

Positive Impact ◽

International Health ◽

Routine Care ◽

Care Organization ◽

Depression Care ◽

Resource Limited Settings ◽

Resource Limited ◽

The Impact

Abstract Background There is a growing literature in support of the effectiveness of task-shared mental health interventions in resource-limited settings globally. However, despite evidence that effect sizes are greater in research studies than actual care, the literature is sparse on the impact of such interventions as delivered in routine care. In this paper, we examine the clinical outcomes of routine depression care in a task-shared mental health system established in rural Haiti by the international health care organization Partners In Health, in collaboration with the Haitian Ministry of Health, following the 2010 earthquake. Methods For patients seeking depression care betw|een January 2016 and December 2019, we conducted mixed-effects longitudinal regression to quantify the effect of depression visit dose on symptoms, incorporating interaction effects to examine the relationship between baseline severity and dose. Results 306 patients attended 2052 visits. Each visit was associated with an average reduction of 1.11 in depression score (range 0–39), controlling for sex, age, and days in treatment (95% CI −1.478 to −0.91; p < 0.001). Patients with more severe symptoms experienced greater improvement as a function of visits (p = 0.04). Psychotherapy was provided less frequently and medication more often than expected for patients with moderate symptoms. Conclusions Our findings support the potential positive impact of scaling up routine mental health services in low- and middle-income countries, despite greater than expected variability in service provision, as well as the importance of understanding potential barriers and facilitators to care as they occur in resource-limited settings.

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Impact of Tocilizumab on Clinical Outcomes in COVID-19-Associated Cytokine Release Syndrome: A Single-Center Experience

Journal of Pharmacy Practice ◽

10.1177/08971900211028208 ◽

2021 ◽

pp. 089719002110282

Author(s):

Karan Raja ◽

Nicole Daniel ◽

Susan Morrison ◽

Ruben Patel ◽

Jessica Gerges ◽

...

Keyword(s):

Clinical Outcomes ◽

Clinical Status ◽

Rank Test ◽

Cytokine Release ◽

Cytokine Release Syndrome ◽

Single Center ◽

Post Dose ◽

Single Center Experience ◽

Signed Rank Test ◽

The Impact

Background: Tocilizumab is an interleukin-6 receptor antagonist hypothesized to blunt the uncontrolled immune response, cytokine release syndrome, in severe COVID-19 and prevent attributable morbidity and mortality. Objective: The objective of this study was to assess the impact of tocilizumab on clinical outcomes in COVID-19-associated cytokine release syndrome. Methods: Single-center, retrospective cohort study assessing sixty-nine adult patients receiving tocilizumab for suspected COVID-19 cytokine release syndrome. The primary outcome was change in WHO clinical status scale on day seven post-dose analyzed using the Wilcoxon signed rank test. Secondary outcomes assessed impact of timing of administration on clinical outcome. Safety analyses included development of neutropenia, thrombocytopenia, transaminitis, and sepsis within 7 days post-dose. Statistical analyses were conducted using Microsoft Excel. Results: No aggregate clinical change was found between day 0 and day 7. Eleven patients improved, twenty-seven worsened, and thirty-one showed no change. Clinical outcomes were weakly correlated with time from symptom onset (rs = 0.21; p = 0.08) or hospital admission (rs = -0.08; p = 0.49) to dose. In-hospital mortality was 63%. Sepsis was diagnosed in 21 patients, five of which were post-dose. Transaminitis, neutropenia, and thrombocytopenia occurred in seven, one, and six patients, respectively. Conclusion: Tocilizumab did not appear to influence clinical outcomes in our study population, irrespective of timing of administration. Adverse events were not considered drug-related.

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