Increased Liver Function Tests Research Articles

The use of elexacaftor/tezacaftor/ivacaftor in patients with cystic fibrosis postliver transplant: A case series.

Cystic fibrosis (CF)-related liver disease (CFLD) manifests as a wide spectrum of hepatobiliary disease and can progress to need liver transplantation. Elexacaftor/tezacaftor/ivacaftor (elx/tez/iva) is a cystic fibrosis transmembrane conductance regulator modulator that has superior efficacy compared to previously approved modulators. Use of elx/tez/iva, should be approached with caution in individuals with CFLD or following liver transplantation due to possible increases in liver function tests (LFTs) and drug-drug interactions with several immunosuppressant medications. The purpose of this case series is to explore if the use of elx/tez/iva is safe and tolerable in patients with CF postliver transplantation. A retrospective case series including patients prescribed elx/tez/iva following liver transplantation and an immunosuppressive regimen consisting of drug therapy metabolized by P-glycoprotein was completed. Ten patients at six CF centers with a median age of 22.1 years (range 14-43.4 years) and the median time from the transplant of 6.9 years (range 0.6-22 years) were included. Most patients (8, 80%) received a reduced or full dose of elx/tez/iva for a mean duration of 10.4 months (range 7-12 months). Fluctuations in LFTs occurred in all patients (10, 100%) and led to therapy discontinuation in two patients (20%). Elx/tez/iva initiation resulted in elevations in tacrolimus trough concentration in seven patients (70%). Most patients who tolerated elx/tez/iva had symptomatic and quality of life improvement, increased body mass index, and maintained or improved lung function. Initiation of elx/tez/iva in patients with CF who received liver transplantation may be safe with clinical benefits.

Q Fever in the Differential Diagnosis of COVID 19 Infection

Coxiella burnetii is an intracellular, Gram-negative bacteria and is the causative agent of Q fever, a zoonosis first described in Australia in 1937. It can cause endemics around the world. People usually get the disease by inhaling the contaminated aerosol produced by infected livestock. Contaminated milk, intradermal inoculation, sexual contact, blood transfusion, and transplacental route may also occur. The infective dose for humans is 1-10 bacteria. It is resistant to environmental conditions and can remain alive in animal wastes such as dust and fertilizer. Acute infection is typically asymptomatic or may manifest as a febrile flu-like illness, pneumonia, hepatitis, and central nervous system (CNS) infection. Q fever outbreaks are often caused by occupational exposure that includes shepherds, animal keepers, veterinarians, slaughterhouses or dairy workers, and laboratory personnel working with C. burnetii. During the course of the disease that cannot be distinguished from other pneumonia clinically; 2-10 fold increase in liver function tests, leukocytosis and thrombocytopenia, erythrocyte sedimentation rate and creatine kinase increase may be observed or laboratory findings may be normal. An immunofluorescent antibody (IFA) test, which is a serological reference method, should be requested from patients suspected for the diagnosis of Q fever.

The effect and clinical significance of using nathanson liver retractor on liver function tests in laparoscopic gastric cancer surgery.

There are very few studies in the literature investigating the changes caused by the Nathanson retractors in liver function tests (LFT) after LG and its clinical significance. The present study investigated the changes made by the Nathanson retractor used during LG on LFT and its clinical significance. The data of 236 patients, who underwent radical gastrectomy for primary gastric cancer at Surgical Oncology Unit in the period between January 2015 and January 2020 were retrospective studied. The patients were divided into two groups: laparoscopic gastrectomy (LG; 136 cases) and open gastrectomy (OG; 106 cases). Patients who have undergone cholecystectomy, with primary or secondary liver tumors, with chronic hepatic disease, who have preoperative high ALT, AST and bilirubin values were excluded from the study. LFT were measured preoperatively and postoperative day 1 (LFT1), LFT3, LFT5 and LFT7. LFT: ALT, AST and Total bilirubin (BIL). ALT1, ALT3, ALT5, ALT7 ALT values and AST1, AST3, AST5 AST values of the patients in the LG group were found to be significantly higher (P <0.001). Mean total bilirubin values of the groups were similar (P >0.05). In order to evaluate how the increase in LFT due to the use of the Nathanson retractors reflected on the patients' clinic, we divided the patients who underwent LG into two groups based on ALT increase in ALT1: Normal and Elevated. The in-hospital mortality rates (P = 0.080) and oral nutrition time (P = 0.913) of the groups were similar. No liver infarction developed in any of the groups. The duration of stay in the ICU was significantly longer in individuals with elevated LFT (P = 0.019). Although the use of the Nathanson retractor during LG causes an increase in liver function tests, this does not cause major clinical problems in patients. Key Words: Gastrectomy; gastric cancer; laparoscopy; liver enzymes; liver dysfunciton.

1018P Characterization of liver function tests following tebentafusp in phase III randomized trial comparing tebentafusp with investigator’s choice in first line metastatic uveal melanoma (mUM)

Tebentafusp (tebe) is a bispecific gp100-targeted T-cell receptor fusion protein that can redirect and activate polyclonal T-cells leading to release of inflammatory mediators. In this randomized phase III study in 1L mUM [NCT03070392], tebe demonstrated OS benefit vs. investigator’s choice (IC). Increases in liver function tests (LFTs) were common; however, gp100 is not expressed on hepatocytes and tebe did not redirect T-cells against normal hepatocytes in vitro. Here we describe LFT kinetics and outcomes for tebe and IC-treated patients.

Macrophage activation syndrome in COVID-19

The novel coronavirus epidemic is characterized by high rates of morbidity and relatively high mortality. Laboratory test results in patients include leukopenia, an increase in liver function tests and ferritin levels reaching hundreds, and sometimes thousands of units. These data remind us about the macrophage activation syndrome (MAC). Secondary hemophagocytic lymphohistiocytosis syndrome, MAC, which pathogenesis is based on a defect in the mechanisms of T-cell cytotoxicity and decreased level of natural killer cells associated with the defect in the perforin-encoding gene as well as hyperproduction of a number of cytokines – interleukin (IL)-1â, tumor necrosis factor-á, etc. by T-lymphocytes and histiocytes, indirectly leading to the activation of macrophages and production of proinflammatory cytokines, in particular IL-6 hyperproduction. MAC is one of "hyperferritinemic syndromes". These disorders have similar clinical and laboratory manifestations, and they also respond to similar treatments, suggesting that hyperferritinemia may be involved in the overall pathogenesis and is characterized by elevated ferritin level and cytokine storm. Despite the fact that data on the immune and inflammatory status in patients with COVID-19 have only started to appear, it is already clear that hyperinflammation and coagulopathy affect the disease severity and increase the risk of death in patients infected with SARS-CoV-2. Hence, understanding the pathogenesis of the novel coronavirus infection can help in its early diagnostics and treatment.

Characterization of liver function tests (LFTs) following tebentafusp (tebe) in previously treated (2L+) metastatic uveal melanoma (mUM) patients (pts).

e21513 Background: Tebe is a bispecific gp100-targeted T cell receptor fusion protein that can redirect polyclonal T cells to target gp100+ cells leading to T cell activation and release of inflammatory mediators. Hepatocytes do not express gp100 and tebe did not redirect T cells against normal hepatocytes in preclinical in vitro studies. However, since most mUM pts have liver metastases, tebe may result in secondary effects from localized tumor-related inflammation. Here we describe LFT kinetics and outcomes for pts in the IMCgp100-102 study (NCT02570308). Methods: 127 HLA-A*02:01+ pts with 2L+ mUM received tebe, administered weekly at the RP2D following intra-patient dose escalation (C1D1: 20μg; C1D8: 30μg; C1D15+: 68μg). Pts were eligible if ALT/AST ≤ 3 x ULN and bilirubin ≤ 1.5 x ULN. LFTs were measured at baseline (BL) and weekly prior to each dose using local laboratories. AE grading was based on CTCAE v4.03. This analysis was conducted on the primary analysis snapshot dated 04Jun20. Results: At BL,125/127 (98%) pts had ALT/AST ≤ grade(G)1 and 122/127 (96%) had liver metastasis. 68/127 (54%) had an increase in post-BL grade for ALT, AST or both. Of these 48/68 (71%) increased to G1, 9/68 (13%) to G2, 7/68 (10%) to G3, and 4/68 (6%) to G4. 67 of these 68 pts (99%) had liver metastasis and most had largest liver metastasis > 3cm (38 pts > 3 cm, 29 pts < 3cm and 1 pt without). ALT/AST increases occurred early in treatment in 36/68 (53%) including at Dose 1 (12/68; 18%), Dose 2 (10/68; 15%), or Dose 3 (14/68; 21%). In the other 32/68 pts (47%), ALT/AST increases occurred at or after Dose 4 (4-65), and most of these events (21/32; 66%) were associated temporally with increase in size of liver metastases. Among the 11 pts with G3/4 ALT/AST increases post-BL, most pts experienced these events early (Doses 1-3) (8/11; 73%) and in the context of either increase in size of liver metastases / disease progression or biliary obstruction (9/11; 82%). Most pts, 60/68 (88%), continued treatment despite an increase in ALT/AST grade. Among 8 pts who discontinued treatment, 3 were due to disease progression and 3 were due to adverse events. Median time for ALT/AST to return to BL was 9 days and there were no temporal increases in albumin or INR. Conclusions: Approximately 1/2 of tebe treated pts experienced an increase in post-BL CTCAE grade for ALT/AST. Among these pts, most ALT/AST increases were mild. Most of the pts with G3/4 ALT/AST increase (9/11) were explained by increase in size of liver metastases or biliary obstruction. Increase in LFT are not unusual at time of disease progression in mUM given high frequency of liver metastases. In summary, ALT/AST increases occurred early in about half of the pts, were generally self-limiting, permitted treatment to continue, and did not appear to impact liver synthetic function (INR/Albumin). Clinical trial information: NCT02570308.

Initial results from a phase 1b study of ORIC-101, a glucocorticoid receptor antagonist, in combination with nab-paclitaxel in patients with advanced solid tumors.

2553 Background: ORIC-101 is a potent and selective, orally bioavailable, small molecule antagonist of the glucocorticoid receptor (GR). Preclinical studies have demonstrated that activation of GR signaling leads to decreased responsiveness to chemotherapeutics (eg, taxanes) and antiandrogens across multiple tumor types. Mechanistically, ORIC-101 inhibits GR transcriptional activity and blocks the prosurvival signals mediated by the activated nuclear hormone receptor. Methods: A 3+3 dose escalation design was used to assess safety, pharmacokinetics (PK), pharmacodynamics (PD), and select the Recommended Phase 2 Dose (RP2D) of ORIC-101 in combination with nab-paclitaxel (nab-pac; NCT03928314). ORIC-101 doses ranging from 80 to 240 mg once daily, given either intermittently or in a continuous dosing regimen, were evaluated in combination with weekly nab-pac at 75 or 100 mg/m2. Plasma PK and PD biomarkers were assessed on day 1 and after repeat dosing. PD modulation in blood-derived peripheral blood mononuclear cells (PBMCs) was assessed by RT-qPCR for GR target genes. Antitumor activity was assessed by RECIST v1.1. Results: 21 patients with 10 different solid tumors, with and without a prior taxane, were treated in 5 cohorts. ORIC-101 exposure increased with dose, with no evidence for drug-drug interaction with nab-pac. In the initial cohort at 240 mg ORIC-101 and 100 mg/m2 nab-pac, 2 patients experienced dose limiting toxicities (DLTs) of Grade 3 fatigue and Grade 4 neutropenia/thrombocytopenia, respectively. No further DLTs were observed in subsequent cohorts and the RP2D was established as 160 mg ORIC-101 dosed once daily continuously for 21 days with nab-pac 75 mg/m2 given on days 1, 8, and 15 of each 28-day cycle, without requirement for prophylactic granulocyte colony-stimulating factor (G-CSF). The most common (> 15%), all grade treatment-related adverse events (AEs) were nausea (38%), diarrhea (33%), fatigue (29%), leukopenia (29%), neutropenia (29%), anemia (24%), and 19% of patients had increased liver function tests and alopecia. Biomarker data demonstrated ORIC-101-induced reduction in GR target gene expression in PBMCs, indicating PD modulation at all dose levels of ORIC-101. Preliminary antitumor activity was observed in 3 taxane-refractory patients with breast, endometrial, and pancreatic cancers. Conclusions: The combination of ORIC-101 and nab-paclitaxel demonstrated an acceptable tolerability profile and does not require prophylactic G-CSF. PK and PD showed no evidence of drug-drug-interaction and demonstrated GR target inhibition. Preliminary antitumor activity was observed in patients with solid tumors that previously progressed on a taxane-containing regimen. Dose expansion is ongoing at the RP2D in dedicated pancreatic, ovarian, triple negative breast cancers, and tissue-agnostic cohorts. Clinical trial information: NCT03928314.

Antitumor activity of lurbinectedin in second-line small cell lung cancer patients who are candidates for re-challenge with the first-line treatment

IntroductionThe National Comprehensive Cancer Network guidelines recommend re-challenge with the first-line treatment for relapsed small cell lung cancer (SCLC) with chemotherapy-free interval (CTFI)≥180 days. A phase II study (NCT02454972) showed remarkable antitumor activity in SCLC patients treated with lurbinectedin 3.2 mg/m2 1 -h intravenous infusion every 3 weeks as second-line therapy. We report results for the pre-planned subset of patients with CTFI ≥ 180 days. Material and MethodsTwenty patients aged ≥18 years with pathologically proven SCLC diagnosis, pretreated with only one prior platinum-containing line, no CNS metastases, and with CTFI ≥ 180 days were evaluated. The primary efficacy endpoint was the overall response rate (ORR) assessed by the Investigators according to RECIST v1.1. ResultsORR was 60.0 % (95 %CI, 36.1−86.9), with a median duration of response of 5.5 months (95 %CI, 2.9−11.2) and disease control rate of 95.0 % (95 %CI, 75.1−99.9). Median progression-free survival was 4.6 months (95 %CI, 2.6−7.3). With a censoring of 55.0 %, the median overall survival was 16.2 months (95 %CI, 9.6-upper level not reached). Of note, 60.9 % and 27.1 % of patients were alive at 1 and 2 years, respectively. The most common grade 3/4 adverse events and laboratory abnormalities were hematological disorders (neutropenia, 55.0 %; anemia; 10.0 % thrombocytopenia, 10.0 %), fatigue (10.0 %) and increased liver function tests (GGT, 10 %; ALT and AP, 5.0 % each). No febrile neutropenia was reported. ConclusionLurbinectedin is an effective treatment for platinum-sensitive relapsed SCLC, especially in patients with CTFI ≥ 180 days, with acceptable safety and tolerability. These encouraging results suggest that lurbinectedin can be another valuable therapeutic option rather than platinum re-challenge.

Biochemical, functional, and histopathologic characterization of lomustine-induced liver injury in dogs.

To characterize the biochemical, functional, and histopathologic changes associated with lomustine-induced liver injury in dogs. I0 healthy purpose-bred sexually intact female hounds. Dogs were randomly assigned to receive lomustine (approx 75 mg/m2, PO, q 21 d for 5 doses) alone (n = 5) or with prednisone (approx 1.5 mg/kg, PO, q 24 h for 12 weeks; 5). For each dog, a CBC, serum biochemical analysis, liver function testing, urinalysis, and ultrasonographic examination of the liver with acquisition of liver biopsy specimens were performed before and at predetermined times during and after lomustine administration. Results were compared between dogs that did and did not receive prednisone. 7 of the I0 dogs developed clinical signs of liver failure. For all dogs, serum alanine aminotransferase (ALT) and alkaline phosphatase (ALP) activities, bile acid concentrations, and liver histologic score increased and hepatic reduced glutathione content decreased over time. Peak serum ALT (r = 0.79) and ALP (r = 0.90) activities and bile acid concentration (r = 0.68) were positively correlated with the final histologic score. Prednisone did not appear to have a protective effect on histologic score. In dogs, liver enzyme activities, particularly ALT and ALP activities, should be closely monitored during lomustine treatment and acute increases in those activities may warrant discontinuation of lomustine to mitigate liver injury. Nonspecific ultrasonographic findings and abnormal increases in liver function tests were not detected until the onset of clinical liver failure. Glutathione depletion may have a role in lomustine-induced hepatopathy and warrants further investigation.

VP45.33: A 41‐year‐old multigravida pregnancy with COVID‐19 infection in third trimester: a case of transient deterioration after Caesarean

Caesarean section in mothers infected with COVID-19 may linked to clinical deterioration. Physiological changes in the cardiovascular, respiratory, and coagulation systems may lead to increased risk of morbidity. Our case had a transient deterioration after Caesarean. A 41-year-old multigravida (G6P5), without any underlying medical disease, was refered to our centre at 36 weeks of gestation with complaints of fever, dry cough, shortness of breath and myalgia on 19 March 2020. Her husband's nasopharynx swab test became SARS-COVID positive and had mild symptoms. He was isolated at home. She was admitted due to suspected COVID-19 pneumonia. She was normotensive, febrile, and tachypneic on admission. Her chest CT on admission had bilateral patchy ground-glass features, nasopharyngeal swab for SARS-COVID had a positive result. The laboratory investigation showed lymphocytopenia, increased liver function tests and CRP levels. Antepartum monitoring was reassuring. Treatment with diphenhydramin, azithromycin and kaletra was initiated. Within 24h of admission, she developed acute hypoxemia, tachypenea and decreased O2 saturation and non-reassuring fetal heart rate tracing. An emergency Caesarean section was performed, leading to birth of a liveborn girl weighing 3,100g, Apgar score was 8/10 and 9/10 at 1st and 5th minute, her neonate was isolated and referred to neonatal centre and nasopharyngeal swab was SARS-CoV2 negative. Our patient was transferred to ICU after delivery and continued on oxygen support. 24h later, she decompensated and was intubated. Mechanical ventilation was continued for 6 days and then she was extubed and was managed by NIV for 48h, then on Day 11 she was transferred to ward. On Day 13 her general condition improved and was discharged from hospital on outpatient orders. The mother and her neonate remained healthy during follow-up.

Increasing accrual of minority patients in breast cancer clinical trials.

Black and Hispanic patients participate in clinical trials at lower rates than white patients nationally; lack of diversity in clinical trials prevents appropriate safety and efficacy testing of new treatments in these populations. The Oncology Welcomes New Haven into Trials (OWN IT) initiative at the Yale Cancer Center used a multi-tiered approach to improve breast cancer minority clinical trial accrual through community focus groups, ongoing community outreach, institutional executive council representation, grand rounds presentation, and didactic lectures with healthcare providers. Eligibility criteria of breast cancer trials at Smilow Cancer Center were reviewed using clinicaltrials.gov. Also, an anonymous, 5-min survey was conducted at regular visits with Smilow Breast Center patients to gauge awareness of and access to clinical trials. Survey data were compared to the Yale Cancer Center Clinical Trials Office, Connecticut Tumor Registry, and U.S. Census records. Two-tailed Fisher's tests were used for all analyses. There was a significant increase in the number of minority patients who participated in clinical trials at Smilow Cancer Center from 2016 (95/750) to 2018 (155/944) (p = 0.0325). Two hundred patients participated in the survey; response rate 92%. There was no significant difference in the rate at which patients were invited to participate in clinical trials or the rate at which they declined to participate based on race or ethnicity. Black and Hispanic patients were significantly less likely to be aware of clinical trials than white patients (p < .001). The review of eligibility criteria showed that over half of the studies reviewed had restrictions regarding increased liver function tests, and many restricted the participation of patients with other chronic conditions. Low participation in clinical trials among black and Hispanic patients is likely multifaceted. This study indicated that there are likely structural factors at work which can be modified with institutional effort. The role of patient education regarding clinical trials and accrual should be studied further as should eligibility criteria as a potential barrier to participation.

Extreme anorexia nervosa: medical findings, outcomes, and inferences from a retrospective cohort

BackgroundExtreme anorexia nervosa (AN) is defined as a BMI < 15 kg/m2 in those meeting DSM-V diagnostic criteria for AN. This study seeks to define the frequency of medical complications in this group of patients in order to help inform the care of individuals < 65% ideal body weight who seek treatment for their extreme eating disorders.MethodsThrough retrospective chart review and computerized data collection, we obtained the baseline characteristics and medical findings of 281 adult patients, with AN restricting and binge-purge subtypes, admitted to the ACUTE unit for medical stabilization between May 2013 and August 2018.ResultsIn this population, with a mean admitting BMI of 12.1 kg/m2 (range = 7.5–15.7), 56% admitted with bradycardia, 45% demonstrated increased liver function tests (LFTs) on admission, 64% admitted with leukopenia, 47% with anemia, and 20% presented with thrombocytopenia. During admission, 38% developed hypoglycemia, 35% developed refeeding hypophosphatemia, nearly 33% of patients developed edema, and low bone mineral density was diagnosed in almost 90% of the patients. Highly elevated LFTs (>3x upper limits of normal) predicted hypoglycemia, and low BMI predicted refeeding hypophosphatemia (p = .001).ConclusionsAlthough conclusions drawn from the findings presented in this descriptive study must be tempered by relevant clinical judgement, these findings showcase that patients with extreme AN are at significantly increased risk for many serious medical complications secondary to their state of malnutrition and also with initial refeeding.

A serious complicatıon of liver hydatid cysts in children: cystobiliary fistulas.

We aimed to determine predictive factors for predicting cystobiliary fistulas (CBF) in children after treatment of liver hydatid cyst (LHD). The records of patients who were treated for LHD between 01.06.2009 and 1.06.2019 were retrospectively reviewed. Age, sex, laboratory test results, size and number of cysts, method of first intervention (percutaneous or surgery), whether or not CBF developed and how it was treated were investigated. Among findings, those could be predictive were investigated. Data were evaluated with SPSS 21.0 program, p < 0.05 was considered significant. Of the 97 patients, 48 (49.5%) were male, 49 (50.5%) female, the mean age was 11.2years, Eighty patients had right (82.5%), 13 had left, and 4 had bilobar involvement. As first intervention, surgery was performed in 39 (40.2%); percutaneous treatment was performed in 58 (59.8%) patients. In 8 patients (20.5%) in surgery group and in 6 patients (10.3%) in percutaneous group, totally in 14 patients (14.4%), CBF developed. The mean cyst diameter of CBF-developed group was 114.36mm, and of CBF-undeveloped group was 74.30mm. There was no statistically significant differences between groups in terms of age, sex, involved lobe, other organ involvement, and preoperative results (p > 0.5). There was a significant relationship between the cyst diameter and the rate of CBF development in both surgical and percutaneous groups (p < 0.05). ROC analysis was performed, and the cut-off value for the development of CBF detected as 69mm for children. Since obstructive jaundice seen in adults is not common in children, an increase in liver function tests and bilirubin levels were not seen in our patients. A significant correlation was found only between the size of the cyst and developing CBF. Cysts greater than 69mm have a higher risk of developing CBF after both percutaneous and surgical treatment and should be closely monitored.

TOXICOLOGICAL EFFECTS OF THE ANTIRETROVIRAL DRUG (NEVIRAPINE) ON MALE ALBINO RATS: A GENETIC &amp; HISTOPATHOLOGICAL STUDY

ABSTRACT Nevirapine (NVP) is a non-nucleoside reverse transcriptase inhibitor used in the treatment of HIV infections. It has been reported that NVP has a toxic effect on the liver, kidney and male reproductive system. This study was designed to assess the NVP toxic effects on these tissues (liver, kidney and testis) and its possible genotoxic and mutagenic effects. Forty adult male albino rats were divided into 4 groups (10 rats each): (A) negative control group, (B) positive control group received 1ml/ day of corn oil, (C) NVP1 treated group received 3.6mg (loading dose) of the drug for 2 weeks and (D) NVP2 treated group received the loading dose of the drug for 2 weeks then 7.2 mg (maintenance dose) for 2 weeks more. The results of present study revealed the followings: NVP did not alter the body weight gain or kidney weight, but it increased liver weight in (group C) and decreased testis weight in (group D). NVP caused a high significant increase of liver function tests (serum aspartate transferase, alanine transaminase, alkaline phosphatase and total bilirubin), a high significant decrease in hormonal levels of testes (testosterone, FSH and LH) and no significant difference on kidney function tests (urea and creatinine). Histopathological changes in liver and testis in NVP-treated groups were observed as compared to control groups. Comet assay showed that NVP caused a highly significant damage in blood cells in a dose dependent fashion. This result suggests for the first time that this drug might induce genotoxicity in the whole blood. In conclusion, oral exposure of adult albino rats to NVP at a human therapeutic dose daily for 4 weeks leads to toxic effects on liver and damaging effect on male reproductive system in addition to the genotoxicity.

Toxicity profile of honey and ghee, when taken together in equal ratio

Honey and ghee are an essential component of our diet. They play an important role like anti-inflammatory, antioxidative, antimicrobial, etc. It is written in Charak Samhita that an equal mixture of honey and ghee turn into a harmful component for health. This study was designed to explore the mechanism of toxicity through the biochemical and histological parameters in Charles foster rats (24 rats were used). We have divided these rats into four groups (n = 6) - normal, honey (0.7 ml/100 g bw), ghee (0.7 ml/100 g bw), and honey + ghee (1:1) (1.5 ml/100 g bw). Treatment was given orally for 60 days. All rats were sacrificed on 61 days. Biochemical parameters like liver function test, kidney function test, Oxidative stress, Glycemic, and some protein modification parameters were done in blood plasma. We found weight loss, hair loss, red patches on ear, and increased liver function test, oxidative stress, Amadori product formation, advanced glycation end-product formation, dipeptidyl protease (DPP-4) and decreased incretins (glucagon-like peptide-1(GLP-1) and gastric inhibitory polypeptide (GIP)) in honey + ghee group. H&E and immunohistochemistry results showed mild inflammation in liver tissue but no changes in the kidney, intestine and, pancreas. Thus it concluded that the increased formation of Amadori product, DPP-4 activity and low incretins (GLP-1, GIP) activity resulting high postprandial hyperglycemic response could be collectively responsible for oxidative stress-mediated toxicity of honey and ghee in the equal mixture.

Retrospective Safety Evaluation of a Pharmacist-Assisted Total Dose Iron Sucrose Protocol in Hospital Inpatients With Iron Deficiency Anemia

Background: Intravenous (IV) iron sucrose can be used for iron deficiency anemia (IDA), but little information exists on total dose infusion (TDI) of this drug. At a tertiary hospital, an iron sucrose TDI protocol was implemented with staff pharmacists aiding physicians in appropriate dosing. Objectives: We sought to define the safety and efficacy of this protocol in adults ≥18 years old with IDA. Methods: We conducted a retrospective chart review of patients who received iron sucrose TDI. Inclusion criteria included patients ≥18 years old who were hospitalized and received iron sucrose in doses ≥300 mg. We reviewed the medical record for adverse reactions to any TDI of iron sucrose as well as pre-TDI and post-TDI hemoglobin (Hgb) levels to assess efficacy. Results: A total of 238 patients received iron sucrose TDI for IDA during the study period. One hundred ninety-three (81%) patients were female, and the mean age in our cohort was 60.6 years. Mean pre-TDI Hgb was 8.76 g/dL. The mean total dose of iron sucrose in the total cohort was 680 mg (range: 300-2500 mg). Adverse effects attributable to iron sucrose were reported in 15 patients, with nausea being the most common effect (7/238, 2.9%). When matching patients’ preadmission and postadmission records, a Hgb increase of 2.1 g/L was found (P < .001). No increase in liver function tests was found in any patient. Conclusions: A pharmacist-assisted iron sucrose TDI protocol for patients with IDA successfully increased serum Hgb and was well tolerated. Anaphylaxis was not reported.

892. Risk Factors for Adverse Events in Children Receiving Outpatient Antibiotic Therapy

BackgroundOutpatient parenteral antibiotic therapy (OPAT) can decrease the length of hospital stay but is associated with adverse events (AEs). The purpose of this study was to quantify and identify risk factors for OPAT-associated AEs in children.MethodsThis is a retrospective, single-center study of patients aged ≤21 years discharged on OPAT from January 2016 to April 2019. Only patients with OPAT overseen by the infectious disease service were included. Medication AE’s included: rash, neutropenia, hepatitis, diarrhea, C. difficile infection, increased serum creatinine, or others. Central line AEs included: central line dysfunction, infection, rash around line site, or other. Wilcoxon rank-sum test, Pearson’s χ2 test, Fisher’s exact test, and multivariable logistic regression models were used for analyses.ResultsDemographic information can be found in Table 1. Among 176 patients included in the study, an AE occurred in 69 (39%). In a multivariable logistic regression model adjusting for age, county of residence, duration of OPAT, and duration line was in place, each additional day of antibiotics increased the odds of having a medication or line-related AE by 3% (OR 1.03; 95% CI 1.01–1.06; P = 0.005; Table 2). Medication AEs occurred in 30 patients (17%). The most frequent medication AEs were neutropenia (24%), rash (15%), and increased liver function tests (15%). Patients residing in a Large Fringe Metro area (suburb) had 33% lower odds of having a drug-related AE compared with those in a Large Central Metro area (OR 0.67; 95% CI 0.50 to 0.90; P = 0.008). Line AEs occurred in 46 patients (26%), with 10 patients (21%) experiencing >1 line AE. The most common line AEs were line malfunction (56.5%) and line infection (13%). Seven patients experienced both a medication AE and a central line AE. Of the 176 patients, 20 (11%) were readmitted to the hospital due to medication or line AE and an additional 25 (14%) had a healthcare visit for an AE although did not require admission.ConclusionIn our region, nearly 40% of children experienced an OPAT-associated AE and line AEs were more common than medication AEs. Longer durations of IV therapy was an independent risk factor for AEs. Converting to oral antibiotic therapy as soon as feasible may reduce OPAT-associated AEs. DisclosuresRitu Banerjee, MD, PhD, Accelerate Diagnostics: Grant/Research Support; BioFire: Research Grant; Biomerieux: Research Grant; Roche: Research Grant.

395. Safety and Tolerability of Rifampin in Staphylococcal Orthopedic Infections

BackgroundRifampin is part of optimal combination antimicrobial therapy for staphylococcal foreign-body infections, including periprosthetic joint infections (PJI) in cases of retained prostheses. However, rifampin can have important drug interactions, can cause hepatotoxicity and other organ toxicity, and can induce treatment-limiting side effects. Although rifampin safety and tolerability is well-described in tuberculosis patients, its use in orthopedic infections is poorly described. We therefore analyzed the safety and tolerability of rifampin in patients with staphylococcal hip and knee PJIs treated with implant retention.MethodsA retrospective institutional PJI database was queried to identify all staphylococcal PJI cases treated with implant retention, from 2008 to 2016. Patient demographics, comorbidities, and antibiotic treatment course were collected. The Chi-square or Fisher’s exact test was used for comparisons between rifampin-tolerant (RT) and -intolerant (RI) subgroups.Results80 patients were included, of which 75 (94%) began rifampin. Of the 75 who received rifampin, 23% (17/75) were RI. The median duration of rifampin for RT was 3.0 months (range 1–60) and 0.75 months for RI (range 0.1–3). Reasons for RI included allergies (N = 6), GI toxicity (N = 5), increased liver function tests (N = 2), leukopenia (N = 2), acute kidney injury (N = 1), exacerbated epilepsy (possibly due to low phenytoin; N = 1), and vasculitis (N = 1). Patient age, sex, and Charlson comorbidity index did not predict rifampin intolerance. In 5/80 (6%) patients who never received rifampin, reasons included liver disease, drug interactions, and rifampin resistance. Overall, 27% (22/80) could not be adequately treated with rifampin.ConclusionIn this study cohort of PJI patients, contraindications to rifampin initiation were infrequent, but discontinuation due to intolerance, allergy, or toxicity occurred in nearly a quarter of patients. Drug-drug interactions can preclude its use, or may cause important medication switches in critical areas such as anticoagulation, epilepsy treatment, and HIV care. Research into the anti-staphylococcal efficacy and safety of alternative rifamycins (such as rifabutin and rifapentine) in patients with staphylococcal hardware infections is warranted.Disclosures All authors: No reported disclosures.

SUPRATHERAPEUTIC PT-INR IN A PATIENT ON CRIZOTINIB FOR STAGE IV NON-SMALL CELL LUNG CANCER

SESSION TITLE: Monday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM INTRODUCTION: Advanced stage non-small cell lung cancer (NSCLC) has classically been managed by systemic chemotherapy agents. These agents had varying level of success but were also associated with several adverse effects. The advent of more targeted agents such as Crizotinb, however, paved the way for anti-cancer medications that preferentially attacked cancer cells and spared normal cells [1]. As these new targeted medications are increasingly used, new adverse events, not previously seen during clinical trials are discovered. Here, we discuss a patient on Crizotinib for stage IV NSCLC presenting with supratherapEutic PT-INR while on Warfarin for atrial fibrillation and a recent aortic valve replacement. CASE PRESENTATION: A 90-year-old male anticoagulated with warfarin 5mg daily for a history of atrial fibrillation and an aortic valve replacement 14 months prior to presentation initially presented to the emergency department for a fall following an orthostatic near-syncopal episode. The patient had been started on Crizotinb for ALK-positive Stage IV lung adenocarcinoma with metastasis to liver and right adrenal gland 3 months prior to presentation. On presentation, the patient’s PT-INR was noted to be 5.9 despite no recent changes in his dose of warfarin or in his diet. A CT scan detected a 10x10cm intramuscular hematoma at the site of trauma in the left gluteal region. Warfarin was held on presentation which led to a precipitous drop in PT-INR 72 hours following presentation. Warfarin therapy was then re-initiated with a much lower dose to achieve the same therapeutic PT-INR. Crizotinib therapy was not interrupted during the hospitalization. DISCUSSION: The USFDA approved Crizotinib in 2011 for the treatment of late-stage ALK-positive NSCLC [2]. Common side effects of the medication are nausea, diarrhea, neutropenia, and increased liver function tests [3]. In the case of our patient, an interaction between Crizotinib and Warfarin was noted and led to a supratherapeutic PT-INR with a consequent hematoma secondary to a fall. This interaction was mentioned only once in literature before in a similar patient who experienced a 1.5-fold increase in PT-INR within 7 days of starting Crizotinib [3]. It is proposed that CYP3A4/5 (which metabolizes Warfarin) is inhibited by Crizotinib [3]. Therefore, Crizotinib use can potentiate the anticoagulant effect of Warfarin by increasing its half-life (evidenced by the precipitous drop of PT-INR following 72 hours in our patient). CONCLUSIONS: While this specific drug-drug interaction has not been commonly reported, it does merit closer monitoring of PT-INR in patients concurrently taking both medications, especially the elderly population and those who are prone to falls. Reference #1: Sahu A, Prabhash K, Noronha V, Joshi A, Desai S. Crizotinib: A comprehensive review. South Asian J Cancer. 2013;2(2):91-7. Reference #2: FDA approves Xalkori with companion diagnostic for a type of late-stage lung cancer". U.S. Food and Drug Administration. Reference #3: Kubomura Y, Ise Y, Wako T, Katayama S, Noro R, Kubota K. A Drug Interaction between Crizotinib and Warfarin in Non-Small-Cell Lung Cancer: A Case Report. J Nippon Med Sch. 2017;84(6):291-293. https://doi.org/10.1272/jnms.84.291. PubMed PMID: 29279560. DISCLOSURES: No relevant relationships by Brian Boden, source=Web Response No relevant relationships by Samer Ibrahim, source=Web Response No relevant relationships by Konstadinos Spyris, source=Admin input

Oral 5-aminosalicylic acid for maintenance of surgically-induced remission in Crohn's disease.

Background The prevention of relapse is a major issue in the management of Crohn's disease. Corticosteroids, the mainstay of treatment of acute exacerbations, are not effective for maintenance of remission and its chronic use is limited by numerous adverse events. Randomised controlled trials assessing the efficacy of oral 5-aminosalicylic acid (5-ASA) agents for maintenance of medically-induced remission in Crohn's disease have produced conflicting results. Objectives To conduct a systematic review to evaluate the efficacy and safety of oral 5-ASA agents for the maintenance of medically-induced remission in Crohn's disease. Search methods We searched MEDLINE, EMBASE, CENTRAL and the IBD Group Specialized Register from inception to 8 June 2016. We also searched reference lists and conference proceedings. Selection criteria We included randomised controlled trials that compared oral 5-ASA agents to either placebo or sulphasalazine in patients with quiescent Crohn's disease. The trials had to have a treatment duration of at least six months. Data collection and analysis Two authors independently extracted data and performed the risk of bias assessment. Any disagreements were resolved by discussion and consensus. The primary outcome measure was the occurrence of relapse as defined by the primary studies. Secondary outcomes included time to relapse, adverse events, withdrawal due to adverse events and serious adverse events. We calculated the pooled risk ratio (RR) and corresponding 95% confidence interval (95% CI) using a fixed-effect model. All data were analysed on an intention-to-treat basis and drop-outs were considered to be relapses. Sensitivity analyses included an available case analysis where drop-outs were ignored and using a random-effects model. We evaluated the overall quality of the evidence supporting the outcomes using the GRADE criteria. Main results Twelve studies (2146 participants) that compared 5-ASA to placebo were included. We did not identify any studies that compared sulphasalazine to placebo. Seven studies were judged to be at low risk of bias. The other studies were judged to have an unclear risk of bias for various items due to insufficient details to allow for a judgement. There was no statistically significant difference in relapse rates at 12 months. Fifty-three per cent (526/998) of 5-ASA patients (dose 1.6 g to 4 g/day) relapsed at 12 months compared to 54% (544/1016) of placebo patients (RR 0.98, 95% CI 0.91 to 1.07; 11 studies; 2014 patients; moderate-quality evidence). Sensitivity analyses based on an available case analysis and a random-effects model had no impact on the results. One study found no difference in relapse rates at 24 months. Fifty-four per cent (31/57) of 5-ASA patients (dose 2 g/day) relapsed at 24 months compared to 58% (36/62) of placebo patients (RR 0.94, 95% CI 0.68 to 1.29, 119 patients; low-quality evidence). One paediatric study found no statistically significant difference in relapse rates at 12 months. Sixty-two per cent (29/47) of paediatric 5-ASA patients (dose 50 mg/kg/day) relapsed at 12 months compared to 64% (35/55) of paediatric placebo patients (RR 0.97, 95% CI 0.72 to 1.31; 102 patients; moderate-quality evidence). There was no statistically significant difference in the proportion of patients who experienced an adverse event, withdrawal due to adverse events or serious adverse events. Thirty-four per cent (307/900) of 5-ASA patients had at least one adverse event compared to 33% (301/914) of placebo patients (RR 1.05, 95% CI 0.95 to 1.17; 10 studies; 1814 patients). Fourteen per cent (127/917) of 5-ASA patients withdrew due to adverse events compared to 13% (119/916) of placebo patients (RR 1.11, 95% CI 0.88 to 1.38; 9 studies; 1833 patients). One per cent (3/293) of 5-ASA patients had a serious adverse event compared to 0.7% (2/283) of placebo patients (RR 1.43, 95% CI 0.24 to 2.83; 3 studies; 576 patients). Common adverse events reported in the studies included diarrhoea, nausea and vomiting, abdominal pain, headache and skin rash. Authors' conclusions We found no evidence in this review to suggest that oral 5-ASA preparations are superior to placebo for the maintenance of medically-induced remission in patients with Crohn's disease. Additional randomised trials may not be justified.