Institutional Treatment Protocol Research Articles

Current Molecular and Clinical Landscape of ATRT - The Link to Future Therapies.

ATRT is a highly aggressive and rare pediatric CNS tumor of very young children. Its genetic hallmark is bi-allelic inactivation of SMARCB1 encoding INI1. Rarely SMARCA4 encoding BRG1 is affected. Up to 30% are associated with constitutional heterozygous pathogenic variants in one of the two genes, giving rise to the Rhabdoid-Tumor-Predisposition-Syndromes (RTPS) 1 and 2. Characteristic DNA methylation profiles distinguish ATRT from other SMARCB1-deficient entities. Three distinct subtypes ATRT-MYC, -TYR, and -SHH are on record. ATRT-SHH may be further divided into the subgroups ATRT-SHH1A, -SHH1B, and -SHH2. The cure of ATRT remains challenging, notwithstanding an increasing understanding of molecular pathomechanisms and genetic background. The implementation of multimodal institutional treatment protocols has improved prognosis. Regardless of treatment approaches, clinical risk factors such as age, metastases, and DNA methylation subtype affect survival probability. We provide a critical appraisal of current conventional multimodal regimens and emerging targeted treatment approaches investigated in clinical trials and entity-specific registries. Intense treatment approaches featuring radiotherapy (RT) and high-dose chemotherapy (HDCT) face the difficulty of balancing tumor control and treatment-related toxicity. Current approaches focus on minimizing radiation fields by proton beam therapy or to withhold RT in HDCT-only approaches. Still, a 40-75% relapse rate upon first-line treatment reveals the need for novel treatment strategies in primary and even more in recurrent/refractory (r/r) disease. Among targeted treatments, immune checkpoint inhibitors and epigenetically active agents appear most promising. Success remains limited in single agent approaches. We hypothesize that mechanism-informed combination therapy will enhance response, as the low mutational burden of ATRT may contribute to acquiring resistance to single targeted agents. As DNA methylation group-specific gene expression profiles appear to influence response to distinct agents, the future treatment of ATRT should respect clinical and biological heterogeneity in risk group adjusted treatment protocols.

Retained fragmented needle in intravenous drug users: An institutional experience and treatment protocol.

Retained needle fragments can occur in intravenous drug user (IVDU), which can lead to significant morbidity and mortality. The aim of present study is to give an overview of our institutional experience and treatment protocol followed for such patients. IVDU with retained fragment of fractured needle were taken from the patient presenting in Emergency, Medicine and CTVS departments with history of IVDU, from January 2019 to December 2020. Six patients were found with retained broken needles. Detailed history, examination and investigations were done. The needle was removed under local anaesthesia successfully in all patients. IVDU with retained broken needle poses risk for catastrophic complications along with possibility of local complications. A systematic approach in managing such patients is required. These broken needles can be successfully retrieved as day care procedure. Lastly, IVDUs with fractured needles pose threat to the caregivers who should take caution to avoid iatrogenic injury.

An Institutional Standardised Protocol for the Treatment of Acute Displaced Midshaft Clavicle Fractures (ADMCFs): Conservative or Surgical Management for Active Patients?

Background and Objectives: The treatment of acute displaced midshaft clavicle fractures (ADMCFs) is still under debate. The aim of this study was to verify the effectiveness of our institutional protocol by comparing the clinical and radiographic outcomes of two groups of patients with ADMCFs treated operatively and non-operatively. Materials and Methods: active patients with a traumatic, isolated non-pathological ADMCF with at least 1-year clinical and radiographic follow up were included. Surgical treatment was performed in the cases where the residual displacement was higher than 140% after the application of a figure-of-eight bandage (F8-B). All other cases were treated conservatively with a F8-B. A total of 134 patients were enrolled and divided into two groups: surgical and conservative groups, with 59 and 75 patients, respectively. Radiological and clinical parameters were evaluated. Results: Good clinical (Constant-Murley Score, the Quick Disability of the Arm, Shoulder and Hand score, and VAS satisfaction) and radiographic outcomes (initial and residual shortening, initial and residual displacement) were obtained for ADMCFs in both groups. Multivariate analysis showed that patients treated conservatively had better clinical outcomes compared to surgically treated patients (p < 0.001). Return to sports was longer in those treated with surgery. Initial shortening was found to impact clinical outcomes as well as initial displacement. None of the patients showed signs of non-union in both groups. Conclusions: Very good mid-term clinical results can be obtained in adult patients with ADMCFs, conservatively or operatively managed, by applying our institutional treatment protocol based on objective radiographic parameters evaluated in the ER.

Reconstruction of partial hypopharyngeal defects following total laryngectomy: Pectoralis major myofascial versus myocutaneous flaps

To date, few comparative studies exist for partial hypopharyngeal defect reconstruction following total laryngectomy. In the absence of objective evidence from comparative studies, the ideal flap choice remains controversial, leading to heterogeneity in institutional treatment protocols. Comparative studies between different reconstructive techniques are required. Therefore, this study compared postoperative outcomes of pectoralis major myocutaneous (PMMC) and myofascial (PMMF) flaps. A single-center retrospective cohort study was performed between 2000 and 2022, which included all consecutive patients who underwent a PMMC or PMMF flap reconstruction following total laryngectomy and partial hypopharyngectomy. Primary outcomes were suture line leakages (conservative management), fistulas (surgical management), and strictures. Secondary outcomes included flap failure, donor-site morbidity, and the start of oral intake. In total, 122 patients were included (109 PMMC and 13 PMMF flap reconstructions). The incidence of suture line leakage was significantly higher (p=0.007) after PMMC flaps (57%) compared with PMMF flaps (15%). Between PMMC and PMMF flaps, fistula (19% vs. 0%) and stricture rates (22% vs. 15%) did not differ significantly. No differences in flap failure, donor-site morbidity, or start of oral intake were observed. PMMF flaps have inherent advantages (e.g., reduced bulk, increased pliability) over conventional PMMC flaps and have non-inferior results compared to the latter in terms of postoperative complications. Although the final choice for reconstruction should be patient-tailored, a PMMF flap can be considered a reliable primary choice that is feasible in most patients.

Intracerebral Hemorrhage in Patients with COVID-19 Infection

Introduction: Thrombotic manifestations, such as deep vein thrombosis, pulmonary embolism, and rarely ischemic stroke, have been identified as disease complications of COVID-19. However, less is known about bleeding complications of COVID-19. While COVID-19-related intracerebral hemorrhage (ICH) has been described in the literature, the underlying risk factors are poorly understood. Methods: We performed a retrospective observational study of consecutively admitted ICH patients in the Mount Sinai Health System in New York, NY. We compared demographic variables, medical comorbidities, in-hospital treatments, and time to diagnosis between COVID-19-positive and COVID-19-negative cohorts. Results: Forty-seven patients were diagnosed with ICH, and of these, 31.9% (n=15) were COVID-19-positive. There were no significant differences in age, race-ethnicity, or cardiovascular risk factors. However, a higher proportion of patients with COVID-19 had a history of obesity, defined as BMI ≥ 30 (73.3% vs. 30.0%, p=0.01). For the COVID-19-negative cohort mean days from presenting symptom onset to ICH diagnosis was 1.4 (95% CI -1.3-3.9). For the COVID-19-positive cohort, ICH was diagnosed an average of 7.9 days from hospital admission (95% CI 2.6-13.3) and 12.3 days from presenting symptom onset (95% CI 5.6-19.0). Of the COVID-19-negative patients, 94% had an admitting diagnosis of ICH, while only 40% of COVID-19-positive patients had an admitting diagnosis of ICH. At the time of this study, the MSHS used a COVID-19 anticoagulation algorithm that recommended consideration of treatment-dose anticoagulation for patients with moderate or severe COVID-19. Patients with severe or worsening respiratory status (based on oxygen requirement, elevations in D-dimer, creatinine, or C-reactive protein) were recommended to be treated with moderate dose anticoagulation (enoxaparin 1 mg/kg every 24 hours) and the recommendation for all COVID-19 ICU patients was treatment dose anticoagulation (enoxaparin 1 mg/kg every 12 hours or apixaban). Forty percent (40%) of patients in the COVID-19-positive cohort were on full-dose anticoagulation at the time of ICH compared to <10% in the COVID-19-negative cohort. Of the COVID-19-positive cohort on full-dose anticoagulation, one-third were on full-dose anticoagulation due to institutional COVID-19 treatment protocols. The rest were treated with anticoagulation for other indications, most commonly atrial fibrillation. Nearly 60% of COVID-19 patients who suffered ICH were not taking full dose anticoagulation. Table 1 summarizes laboratory values among the COVID-19-positive cohort compared to the COVID-19-negative cohort. At the time closest to ICH discovery, mean coagulation markers were slightly elevated (PT 16.5±4.2, PTT 42.9±23.3) compared to the COVID-19-negative cohort (PT 14.6±2.1, PTT 29.0±7.0, p=0.06 and 0.003 respectively), although INR did not significantly differ between the two groups (1.4±0.4 vs. 2.1±4.9). Hemoglobin, hematocrit, white blood cell, and platelet counts were abnormal in >50% of COVID-19-positive patients, compared to approximately 50% or less in COVID-19-negative patients. Inflammatory parameters were elevated in the majority of COVID-19 patients, including C-reactive protein, erythrocyte sedimentation rate, d-dimer, lactate dehydrogenase, fibrinogen, and interleukin-6. The peak CRP in COVID-19 patients (150.5±133.7) was markedly elevated compared to COVID-19-negative patients (42.9±95.2, p=0.06). Conclusions: The admitting diagnosis and time to ICH diagnosis suggest that ICH in COVID-19 is not typically the presenting manifestation of the disease and is more commonly seen in severe disease requiring prolonged hospitalization. Patients with COVID-19 and ICH were more likely to be receiving full-dose anticoagulation than their COVID-19 negative counterparts. ICH in COVID-19 patients is potentially related to anticoagulation, not an underlying inflammatory state or consumptive coagulopathy, and underscores the need for careful consideration of anticoagulation in COVID-19 patients. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Epidemiology of Community-Acquired Sepsis: Data from an E-Sepsis Registry of a Tertiary Care Center in South India.

The study aims to characterize community-acquired sepsis patients admitted to our 1300-bedded tertiary care hospital in South India from the Surviving Sepsis Campaign (SSC) guideline-compliant e-sepsis registry stratified by focus of infection. The prospective observational study recruited 1009 adult sepsis patients presenting to the emergency department at the center based on Sepsis-2 criteria for a period of three years. Of the patients, 41% were between 61 and 80 years with a mean age of 57.37 ± 13.5%. A total of 13.5% (136) was under septic shock and in-hospital mortality for the study cohort was 25%. The 3 h and 6 h bundle compliance rates observed were 37% and 49%, respectively, without significant survival benefits. Predictors of mortality among patients with bloodstream infections were septic shock (p = 0.01, OR 2.4, 95% CI 1.23-4.79) and neutrophil-to-lymphocyte ratio (p = 0.008, OR 1.01, 95% CI 1.009-1.066). The presence of Acinetobacter (p = 0.005, OR 4.07, 95% CI 1.37-12.09), Candida non-albicans (p = 0.001, OR16.02, 95% CI 3.0-84.2) and septic shock (p = 0.071, OR 2.5, 95% CI 0.97-6.6) were significant predictors of mortality in patients with community-acquired pneumonia. The registry has proven to be a key data source detailing regional microbial etiology and clinical outcomes of adult sepsis patients, enabling comprehensive evaluation of regional community-acquired sepsis to tailor institutional sepsis treatment protocols.

Intensity Modulated Radiotherapy on a Novel Ring Gantry-Based Linac with Integrated Dual PET-CT Imaging Systems: Dosimetric Plan Comparison and Initial Clinical Delivery Experience

<h3>Purpose/Objective(s)</h3> This study aims to report our initial clinical experience on using a new external-beam radiotherapy delivery system on a ring gantry with dual PET-CT imaging capabilities for IMRT treatments at different anatomical sites. The study also evaluates the system's plan quality compared to an existing ring gantry-based Linac. This new external-beam radiotherapy delivery system has the potential to be used for biology-guided radiotherapy. <h3>Materials/Methods</h3> We performed a single-institution retrospective review of patients treated on the machine since commissioning. The initial five patients treated to a thoracic site and five patients treated to a pelvic site were included in this study. The dose per fraction ranged from 1.8 to 3.0 Gy. The treatment plans for the machine used a 2-cm jaw size along the longitudinal direction and used the IMRT delivery mode. A 64-leaf binary MLC was used to modulate a flattening filter free 6-MV photon beam. A helical tomotherapy plan (HT plan) using a 2.5-cm jaw size was generated for each RFX plan to serve as the backup plan in clinical treatments. Dosimetric parameters used in institutional treatment protocols were compared between RFX plans and HT plans. Daily delivery records were reviewed, and actual beam-on time was compared between the two machine types. <h3>Results</h3> On average, 12 dosimetric parameters (range: 7 – 14) for critical organs and the primary PTV were used in each treatment plan as clinically relevant planning optimization parameters and were analyzed in this study. Among the critical organ dose parameters, 19 (22.4%) dosimetric parameters were lower by more than 10% in the study's plans compared to the HT plans, while 11 (12.9%) dosimetric parameters were higher by more than 10% in the study's plans compared to the HT plans. The other dosimetric parameters had less than 10% or no clinically relevant difference between the two plans. There was no statistically significant difference in integrated dose between the new machine and HT plans. All the plans were normalized so that the prescription dose covered 95% of the primary planning target volume (PTV). The average D_mean of the primary PTV were 103.5±1.1% and 102.6±0.8% of the prescription dose in the new external-beam radiotherapy delivery system and HT plans, respectively, and the average D(1%) of the primary PTV (dose covering the hottest 1% of the PTV) were 107.1±2.0% and 105.2%±1.6% in the new external-beam radiotherapy delivery system and HT plans, respectively (two-tailed p-value = 0.06 in the paired t-test). The beam-on time was not significantly different between the two machines. The average daily beam-on time was 438.8±151.2 seconds and 427.6±183.1 seconds with the new external-beam radiotherapy delivery system and HT systems, respectively (two-tailed p-value = 0.76 in the paired t-test). <h3>Conclusion</h3> Our initial clinical experience with the external-beam radiotherapy delivery system showed that image guided IMRT could be delivered to different anatomical sites with adequate clinical workflow efficiency. The new machine achieved clinically comparable treatment plan quality compared to helical tomotherapy. The beam-on time was comparable to that on helical tomotherapy.

314.5: The Difference Between Delta and Omicron Variants in Solid Organ Transplant Recipients

Introduction: Solid Organ Transplant (SOT) recipients are vulnerable to SARS-CoV-2 infection. Delta variant has been reported to have worse outcomes as compared to other variants to date. The Omicron variant has been reported more transmissible but less virulent in general population. However, this phenomenon has not been validated in SOT recipients. Method: This is a retrospective cohort study, conducted in two phases, between July 1st and December 10th, 2021(Delta dominant phase), and January 1st and January 31st, 2022 (Omicron dominant phase) in one of the biggest SOT centers in the United States. Patient demographics including transplanted organ, immunosuppressive medication, vaccination status, and treatment modalities were obtained. We also compared clinical outcomes including hospitalization, ICU admission rate and mortality between two groups. Chi squared or fisher’s exact test were performed for categorical variables, whichever appropriate. For continuous variables, Mann Whitney U-test was performed. Multiple logistic regression model with stepwise backward elimination was developed to identify the risk factors for mortality. We put variables whose p value was less than 0.2. Of note, the institutional treatment protocol has not changed during the study period. Result: We identified 64 and 95 SOT recipients while delta and omicron variants were dominant, respectively. The rate of kidney transplant, age, gender, African American race, and the rate of at least received one dose vaccination were not significantly different between two groups. Of note, the hospital admission rate (68.8% vs 36.2%, p<0.001), ICU admission rate (20.3% vs. 6.3%, p=0.012), and mortality (20.9% vs. 4.2%) were higher during the delta variant versus omicron variant phase. For the risk factor analysis for mortality, we put age, African American race, COVID-19 variant, kidney transplant and vaccination status into multiple logistic regression model. Finally, delta variant was the only statistical significant risk factor for mortality (p<0.001, Odds ratio 9.35, 95% confidence interval 2.52-34.5). Conclusion: This is the first study comparing the outcomes between Delta variant dominant and Omicron variant dominant phase in SOT recipients. Even though there was no treatment protocol changed, the identified risk factor for mortality was delta variant dominant phase. However, still, the hospital admission rate (36.2%) should have been observed while Omicron variant phase and required significant aggressive treatment. Thus, we should prepare and may need to change the treatment protocol based on the variant in the future.

Management of Displaced Midshaft Clavicle Fractures with Figure-of-Eight Bandage: The Impact of Residual Shortening on Shoulder Function.

The treatment of displaced midshaft clavicle fractures (MCFs) is still controversial. The aims of our study were to evaluate clinical and radiological outcomes and complications of patients with displaced MCFs managed nonoperatively and to identify potential predictive factors of worse clinical outcomes. Seventy-five patients with displaced MCFs were enrolled and treated nonoperatively with a figure-of-eight bandage (F8-B). Initial shortening (IS) and displacement (ID) of fragments were radiographically evaluated at the time of diagnosis and immediately after F8-B application by residual shortening (RS) and displacement (RD). The clavicle shortening ratio was evaluated clinically at last follow-up. Functional outcomes were assessed using Constant (CS), q-DASH, DASH work and DASH sport scores. Cosmetic outcomes and rate of complications were evaluated. Good to very good mid-term clinical results were achieved by using the institutional treatment protocol. Multiple regression identified RS as an independent predictor of shoulder function, while RD affects fracture healing. These findings support the efficacy of our institutional protocol and thus could be useful for orthopedic surgeons during the decision-making process.

Clinical Profile and Short Term Outcome of Acute Encephalitis Syndrome in Children: An Observational Study from a Tertiary Care Centre, Tripura, India

Introduction: Acute Encephalitis Syndrome (AES) is a group of neurologic manifestation caused by wide range of microbes, chemicals and toxins. Japanese Encephalitis Virus (JEV) is the major cause of AES in India. Isolation of aetiological agent in AES cases presents a fundamental challenge to prevention and management. Lack of study on AES in the paediatric population of Tripura prompted the authors to take up this study. Aim: To determine the clinical profile and short term outcome of children with AES from Tripura, India. Materials and Methods: This hospital-based cross-sectional observational study was conducted from November 2017 to April 2019 in the Department of Paediatrics at Agartala Government Medical College (AGMC), Tripura, India. Total 100 children, from 1 month to 12 years of age, fulfilling definition of AES were enrolled in the study. All the cases were managed as per institutional treatment protocol and were followed-up at 1 and 3 months following discharge. Case record, patient profile records and reports of investigations were the study tools. Chi-square test and Fisher’s-exact test were used as per applicability to test the significance of difference of proportions using Statistical Package for the Social Sciences (SPSS) version 15.0. The difference was considered significant for a p-value &lt;0.05. Results: Out of total, 30 patients (30%) were in 9-12 years age group, with slight male preponderance (1.1:1). Total 72 cases (72%) were from rural area. Common clinical features were fever, altered sensorium, seizures, irritability, abnormal movement, pallor, papilloedema, and lethargy. Abnormal laboratory parameters included leucocytosis (62%), anaemia (27%), hyponatremia (35%), and hypoglycaemia (16%) and elevated liver enzymes (15%). IgM serology was positive for JEV (19%), scrub typhus (6%), herpes simplex virus (2%), dengue (2%), measles (1%), and enterovirus (1%). Magnetic resonance imaging brain was normal in 37% of the cases. About 54% of the cases recovered completely, 20% of the cases died and remaining 26% survived with sequelae. Conclusion: AES is common among older male children from the rural area. Serologically JEV is most common cause. Total 54% cases recovered completely. Proportion of death and residual sequelae were higher in the JEV category. The observations of the study indicate need of extensive studies and scaling up of JE vaccination.

Low- Versus High-Dose Methylprednisolone in Adult Patients With Coronavirus Disease 2019: Less Is More

BackgroundCorticosteroids use in severe coronavirus disease 2019 (COVID-19) improves survival; however, the optimal dose is not established. We aim to evaluate clinical outcomes in patients with severe COVID-19 receiving high-dose corticosteroids (HDC) versus low-dose corticosteroids (LDC).MethodsThis was a quasi-experimental study conducted at a large, quaternary care center in Michigan. A corticosteroid dose change was implemented in the standardized institutional treatment protocol on November 17, 2020. All patients admitted with severe COVID-19 that received corticosteroids were included. Consecutive patients in the HDC group (September 1 to November 15, 2020) were compared to the LDC group (November 30, 2020 to January 20, 2021). High-dose corticosteroids was defined as 80 mg of methylprednisolone daily in 2 divided doses, and LDC was defined as 32–40 mg of methylprednisolone daily in 2 divided doses. The primary outcome was all-cause 28-day mortality. Secondary outcomes included progression to mechanical ventilation, hospital length of stay (LOS), discharge on supplemental oxygen, and corticosteroid-associated adverse events.ResultsFour-hundred seventy patients were included: 218 (46%) and 252 (54%) in the HDC and LDC groups, respectively. No difference was observed in 28-day mortality (14.5% vs 13.5%, P = .712). This finding remained intact when controlling for additional variables (odds ratio, 0.947; confidence interval, 0.515–1.742; P = .861). Median hospital LOS was 6 and 5 days in the HDC and LDC groups, respectively (P < .001). No differences were noted in any of the other secondary outcomes.ConclusionsLow-dose methylprednisolone had comparable outcomes including mortality to high-dose methylprednisolone for the treatment of severe COVID-19.

Cognitive and Adaptive Functioning in Youth With Retinoblastoma: A Longitudinal Investigation Through 10 Years of Age.

To describe the trajectory of cognitive and adaptive functioning in pediatric patients with retinoblastoma from diagnosis through age 10. This is an extension of a previous report that discussed findings from diagnosis through age 5. Ninety-eight participants with retinoblastoma completed psychological assessments as part of their enrollment on an institutional treatment protocol, with 73 completing an additional assessment at age 10. Trajectories of adaptive and cognitive functioning were determined, with data analyzed by treatment strata, and patients with 13q- analyzed separately. Longitudinal trajectories identified a significant change point in trends at age 5, with functioning declining from diagnosis through age 5 and then increasing from age 5 to age 10. This pattern was observed for all strata for adaptive functioning, but only for enucleation-only patients (strata C low) for cognitive functioning. Cognitive trajectories were also influenced by laterality and enucleation status. At age 10, overall functioning was generally within the average range, although estimated intelligence quotient was significantly below the normative mean for enucleation-only (C low) patients. Patients with 13q- demonstrated very low functioning, but few analyses were significant because of small sample size. The results generally indicate that previously demonstrated declines in functioning from diagnosis through age 5 improve by age 10. However, these early declines, as well as the continuous difficulties observed in patients treated with enucleation only, suggest the need for early intervention services for young patients with retinoblastoma. Continuous monitoring of the psychological functioning of patients with retinoblastoma, increased awareness of risk factors such as unilateral disease, enucleation, race, and surgery-only treatment plans, and referral to Early Intervention for all patients are indicated.

A New Era of Pain Management: Finding the Moral Frameworks

Treating the pain of those who suffer has long been held as a moral obligation of nurses. But which moral frameworks support pain management in an era of opioid abuse, increased patient autonomy, and moral pluralism? Changes in the public and professional moral viewpoint regarding pain contribute to changes in government and institutional policies and treatment protocols. New practice protocols and pain management policies may use different moral underpinnings. Moral clarity in policy and treatment protocols can prevent confusion over what is right for patients with pain, thus preventing nurse moral distress, patient stigma, and suboptimal pain care. The aims of this presentation are 1) to introduce nurses to the moral theories/frameworks that may inform pain management policies and practice, and 2) encourage nurses to begin to ask pertinent and effective moral and ethical questions when making pain management practice and policy decisions.

How Are Emerging Data Translated Into Clinical Practice? A Mixed Methods Investigation of Coronavirus Disease 2019 Institutional Treatment Protocols.

BackgroundEarly in the coronavirus disease 2019 (COVID-19) pandemic, there was minimal data to guide treatment, and we lacked understanding of how clinicians translated this limited evidence base for potential therapeutics to bedside care. Our objective was to systematically determine how emerging data about COVID-19 treatments was implemented by analyzing institutional treatment protocols.MethodsTreatment protocols from North American healthcare facilities and recommendations from guideline-issuing bodies were collected. Qualitative data on treatment regimens and their applications were extracted using an adapted National Institutes of Health/US Food and Drug Administration experimental therapeutics framework. Structured data on risk factor and severity of illness scoring systems were extracted and analyzed using descriptive statistics.ResultsWe extracted data from 105 independent protocols. Guideline-issuing organizations published recommendations after the initial peak of the pandemic in many regions and generally recommended clinical trial referral, with limited additional guidance. Facility-specific protocols favored offering some treatment (96.8%, N = 92 of 95), most commonly, hydroxychloroquine (90.5%), followed by remdesivir and interleukin-6 inhibitors. Recommendation for clinical trial enrollment was limited largely to academic medical centers (19 of 52 vs 9 of 43 community/Veterans Affairs [VA]), which were more likely to have access to research studies. Other themes identified included urgent protocol development, plans for rapid updates, contradictory statements, and entirely missing sections, with section headings but no content other than “in process.”ConclusionsIn the COVID-19 pandemic, emerging information was rapidly implemented by institutions into clinical practice and, unlike recommendations from guideline-issuing bodies, heavily favored administering some form of therapy. Understanding how and why evidence is translated into clinical care is critical to improve processes for other emerging diseases.

Taurine as an adjunct therapy for early left ventricular recovery in peripartum cardiomyopathy

Background and Aims: The pathophysiology of peripartum cardiomyopathy is not fully understood. Despite standard medical therapy, both morbidity and mortality remain high. Restoration of inflammatory cytokine balance may hold promise for therapy. Taurine has a powerful immune-modulatory and anti-inflammatory in addition to positive inotropic effect. This study evaluates the effect of taurine infusion on clinical status, left ventricular function, circulating plasma levels of N-terminal brain natriuretic peptide and C-reactive protein in women with peripartum cardiomyopathy. Methods: Forty women with peripartum cardiomyopathy admitted postpartum to the ICU were randomly assigned to one of two groups (20 in each group): Group T received taurine infusion and Group C received normal saline infusion over 24 hours for 5 days. Both groups received standard heart failure therapy according the institutional treatment protocol. Results: In the taurine group on day 5, there was a significant reduction in LVEDD and LVESD and significant increase in LVEF. All patients had an improvement in LVEF of at least 10% and 5 patients had recovery of LVEF to ≥50% on day 5 while the other 15 patients had LVEF 45- 50%. In the control group on day 5, there was non-significant change in LVEDD, LVESD and LVEF and no patient had recovery of LVEF to ≥50% or showed improvement in LVEF more than 10%. NYHA functional class showed significant increase on day 5 in the taurine group compared to the control group. Seventeen patients (85%) in the taurine group showed improvement of the NYHA functional class at day 5. In contrast, only 2 patients (10%) in the control group showed improvement of NYHA functional class at day 5. Conclusion: Early addition of taurine infusion to standard heart failure therapy improves both; echocardiographic parameters and laboratory parameters but without clinically significant changes in women with peripartum cardiomyopathy.

Use of Remdesivir in Patients With COVID-19 on Hemodialysis: A Study of Safety and Tolerance

BackgroundThere are scarce data regarding the use of remdesivir in patients with severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) and end-stage renal disease as US Food and Drug Administration cautions against its use in patients with an estimated glomerular filtration rate <30 ml/min/1.73m2 unless the potential benefits outweigh the potential risks. We studied the compassionate use and safety profile of remdesivir in patients with end-stage renal disease and moderate to severe SARS-CoV-2 infection.MethodsWe conducted an observational prospective study in 48 dialysis-dependent patients with SARS-CoV-2 infection who received remdesivir as part of institutional treatment protocol. During the treatment period, 100 mg of remdesivir was given 4 hours before hemodialysis sessions. Liver function tests, inflammatory markers such as serum C-reactive protein, serum ferritin and lactate dehydrogenase levels, and oxygen requirement before and after remdesivir treatment were compared.ResultsThere were no events of significant liver function test alterations with the administration of 2 to 6 doses of remdesivir. A significant decline in serum C-reactive protein level (P < 0.001) was noted. More than two thirds (68.57%) of patients showed an improvement in oxygen requirement. Early administration of remdesivir within 48 hours of hospital admission shortened the duration of hospitalization by a mean of 5.5 days (P = 0.001).ConclusionRemdesivir was well tolerated and found safe in our study. If initiated within 48 hours of hospitalization, it reduces recovery time. Assessing the mortality benefits of remdesivir in these patients requires a randomized controlled trial with a larger population.

Ethically Allocating COVID-19 Drugs Via Pre-approval Access and Emergency Use Authorization

Allocating access to unapproved COVID-19 drugs available via Pre-Approval Access pathways or Emergency Use Authorization raises unique challenges at the intersection of clinical care and research. In conditions of scarcity, prioritization approaches should minimize harm, maximize benefit, and promote fairness. To promote continued data collection, patients seeking access to unproven COVID-19 drugs should receive lower priority for allocation when they decline to participate in clinical trials, either of the requested drug or other investigational products, offering a comparable balance of risks and benefits; special attention should be paid to concerns of voluntariness and distrust. In addition, institutional treatment protocols that can contribute more robust real world data should be preferred to single patient requests for access, with priority for inclusion based on traditional clinical allocation criteria relying on available evidence. Fairness demands distribution of these protocols across a diverse range of sites, particularly those serving marginalized populations, among other protections.

Surgical and Clinical Reactivation for Elective Procedures during the COVID-19 Era: A Global Perspective

Surgical and Clinical Reactivation for Elective Procedures during the COVID-19 Era: A Global Perspective

1983. Adherence vs. Non-adherence: Clinical Outcomes of an Antimicrobial Stewardship Directed Treatment Protocol for Clostridioides difficile Infection

BackgroundThe 2018 Infectious Diseases Society of America (IDSA) C. difficile infection (CDI) treatment guideline no longer recommends metronidazole as first-line therapy in adults, instead recommending vancomycin or fidaxomicin. At our 1500-bed academic medical center, a new CDI treatment protocol was initiated by the antimicrobial stewardship program (ASP) to guide treatment based on disease severity and risk factors for recurrence. In this study, we compared the clinical cure rate and 30-day recurrence rate in patients who are adherent and non-adherent to our institutional CDI treatment protocol.MethodsPatients with CDI between September-December 2018 were identified using electronic health record (EHR) reports. A retrospective chart review was conducted to collect the following information: baseline demographics, white blood cell count, CDI severity, and risk factors, etc. Outcome measures included clinical cure rate, 30-day recurrence rate, and global cure rate, stratified by whether treatment was adherent or non-adherent to institutional protocol. Student’s t-test was used for continuous variables. Fisher exact test or Chi-square test was used for categorical variables.ResultsA total of 188 patients (adherent group n = 100; non-adherent group n = 88) were included. Patient demographics and baseline risk factors did not differ between groups. Clinical cure rate was higher in adherent group (P < 0.05), while no significant differences were observed in recurrence and global cure rates between the two groups (Figure 1). The overall protocol adherence rate was 53%. The most common reasons for non-adherence are inappropriate vancomycin dose for fulminant CDI (69%) and insufficient duration of treatment (27%).ConclusionAn ASP directed new CDI treatment protocol was successfully implemented at our institution. Patients treated according to our institutional protocol resulted in a higher overall cure rate than those non-adherent. Global cure and 30-day recurrence rates were similar. An overall protocol adherence rate of 53% is consistent with previously published literature. Future direction to develop an EHR order set with targeted recommendations is anticipated to further improve adherence and clinical outcomes. Disclosures All authors: No reported disclosures.

Abstract P5-15-09: Impact of oncotype dx genetic signature used in early breast cancer. Clinical and economic analisys of a 110 patient cohort treated in the Catalan Oncologic Institute (ICO), Spain

Abstract Introduction Benefit from adjuvant chemotherapy (CT) is doubtful in a high percentage of patients with early breast cancer. The 21-gene recurrence-score (RS) assay (Oncotype DX, Genomic Health) is one gene-expression assay that provide prognostic and predictive information in hormone-receptor (RH) positive breast cancer. The results of the TAILORx study have confirmed that the majority of patients with tumors RH + and HER2 negative can avoid CT without increasing their risk of relapse. From 2012 to 2015 we used Mammaprint (MMP), in our institution and 60% of cases could avoided CT (communicated in SABCS 2015). Since 2017 we use RS for this purpose. Primary Objective To analyze the impact of using RS to change the indication of adjuvant CT. Secondary Objectives To analyze the association between different clinical pathological factors and the RS value, and calculate the difference between the cost of all RS test and the cost in direct expense of the treatment with CT of all patients who could avoid it thanks to the RS Material and methods We analyzed all RS test performed in the three ICO centers during 2017. We sent 112 tumor samples; in 2 samples adequated RNA for RS was not obtained. We compared the adjuvant treatment initially planned according to institutional treatment protocol with the treatment given after RS. We compared the direct economic costs of CT with the costs of the diagnostic test, and performed a logistic regression analysis of some pathological factors and RS value. Results The RS could be determined in 110 of 112 cases, in which there was indication of adjuvant CT. Only 14 patients received CT (12,72%) with the RS value, so CT was avoided in 96 patients (87,28%). The clinical-pathological characteristics of the series are summarized in the table 1. Of the risk factors analyzed, only grade 3 (p 0.001) and PR &amp;lt;20% (p&amp;lt;0.002) showed a statistically significant relationship with a higher probability of RS&amp;gt; 25. No association was found between age, nodal status, tumor diameter, Ki67, Infiltrating Ductal Carcinoma vs neither Infiltrating Lobular Carcinoma nor Lympho-Vascular invasion. The cost of the genetic studies was 180000€ (1636€ each). The cost of each CT schedule (EC x 4 followed by paclitaxel x 12) was 7214€ and the total cost of 96 cases 692590€. Direct costs savings estimated from the reduction in CT treatment were 512590€ Conclusion: Our series shows that RS avoided unnecessary CT in 87% of cases and was more cost-effective than a previous series with MMP. G3 and RP &amp;lt;20 were the only pathological factors associated with an increased risk of RS&amp;gt; 25. Table 1.Patients characteristics and clinical-pathological details from the analyzed tumorsPatient characteristicsAge, mean (range)53,76 (19 – 75)≥50y72 (65.5%)&amp;lt;50y38 (34.5%)HistologyInfiltrating ductal carcinoma88 (80%)Infiltrating lobular carcinoma20 (18,2%)Others2 (1,8%)TNMTumor diameter (mm), mean (range)19,25 (1 – 160)pN058 (52,7%)pN1mic21 (19%)pN131 (28,3%)Hormone receptorsRE 2-100%110 (100%)RP &amp;lt;20%22 (20%)RP ≥20%88 (80%)Ki67 median, mean (range)20, 21 (2-75)Lymphovascular invasionyes9 (8%)no101 (92%)Adjuvant treatmentCT14 (12,72%)Hormonotherapy96 (87,28%) Citation Format: Ferrer M, Dorcas J, Quiroga V, Margelí M, del Barco S, Stradella A, Petit A, Falo C, Viñas G, Romeo M, Villanueva R, Cirauqui B, Vázquez S, Fernández A, Recalde S, Vethencourt A, Soler T, Pérez-Martín X, Gil-Gil M. Impact of oncotype dx genetic signature used in early breast cancer. Clinical and economic analisys of a 110 patient cohort treated in the Catalan Oncologic Institute (ICO), Spain [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-15-09.