Levels of Albumin and Impact on Loop Diuretic and Albumin Co-administration in Heart Failure.

ABSTRACT: Management of heart failure (HF) requires the use of loop diuretics to relieve congestion and improve symptoms. When loop diuretics alone fail to induce adequate diuresis, albumin has been proposed to enhance loop diuretic delivery and promote redistribution of fluid for excretion by the kidneys. Despite the theoretical benefits of albumin, studies suggesting its benefit in HF are scarce and the co-administration of loop diuretics and albumin remains controversial. This retrospective, observational study evaluated patients with HF 18 years or older who received concomitant intravenous loop diuretic and albumin administration. The primary objective was to evaluate the association of serum albumin level with urine output (UOP) in hospitalized patients with HF who received concomitant albumin and loop diuretic therapy. Secondary endpoints included total weight loss after 72 hours, and ICU and hospital lengths of stay. In total, 276 patients were included for analysis. There was no association between initial serum albumin level and 72-hour UOP (coefficient -623.1, 95% confidence interval -1558.6 to 312.4; P = 0.191) or weight difference at 72 hours (coefficient -1.0, 95% confidence interval -2.4 to 0.3; P = 0.131). Lower albumin levels were associated with longer ICU ( P = 0.034) and hospital ( P = 0.039) lengths of stay. Concomitant thiazide diuretic use and increasing loop diuretic doses were associated with increased 72-hour UOP. The results of our study suggests that providers should avoid using baseline albumin levels as guidance for albumin dosing in HF. Given the lack of comparator groups, larger randomized controlled trials should be done to provide a definitive role for albumin to enhance diuresis in patients with HF on intravenous loop diuretics.

C-reactive protein levels associated with COVID-19 outcomes in the United States.

CONTEXT: COVID-19 caused a worldwide pandemic, and there are still many uncertainties about the disease. C-reactive protein (CRP) levels could be utilized as a prognosticator for disease severity in COVID-19 patients. OBJECTIVES: This study aims to determine whether CRP levels are correlated with COVID-19 patient outcomes and length of stay (LoS). METHODS: A retrospective cohort study was conducted utilizing data obtained between March and May 2020. Data were collected by abstracting past medical records through electronic medical records at 10 hospitals within CommonSpirit Health. Patients were included if they had a positive COVID-19 test from a nasopharyngeal swab sample, and if they were admitted and then discharged alive or had in-hospital mortality and were ≥18 years. A total of 541 patients had CRP levels measured and were included in this report. Patient outcome and LoS were the endpoints measured. RESULTS: The 541 patients had their CRP levels measured, as well as the demographic and clinical data required for analysis. While controlling for body mass index (BMI), number of comorbidities, and age, the first CRP was significantly predictive of mortality (p<0.001). The odds ratio for first CRP indicates that for each one-unit increase in CRP, the odds of death increased by 0.007. For LoS, the first CRP was a significant predictor (p<0.001), along with age (p=0.002). The number of comorbidities also predicted LoS (p=0.007), but BMI did not. The coefficient for the first CRP indicates that, for each one-unit increase in CRP, LoS increased 0.003 days. CONCLUSIONS: The results indicate that there is a positive correlation between the CRP levels of COVID-19 patients and their respective outcomes with regard to death and LoS.

Effect of Blood Group on Heart Transplant Waitlist Mortality in the Ventricular Assist Device Era.

The effect of blood group on heart transplant list mortality in the era of continuous flow left ventricular assist devices (VADs) is unknown. We sought to examine mortality from the United Network for Organ Sharing (UNOS) database, with focus on mortality among VAD versus non-VAD recipients according to blood group. The UNOS database from 2007 to 2015 was evaluated to compare the rates of waitlist mortality or delisting for clinical worsening at 1-year postlisting among various blood types based on the presence or absence of durable continuous VAD. Patients with pulsatile VAD, temporary VAD, or with incomplete data were excluded. A total of 16,803 patients met the inclusion criteria. Of these, 2,663 had a HeartMate II or HeartWare VAD implanted before listing or by 365th day of listing. The rate of adverse events on the waitlist, irrespective of VAD, was highest among group O patients (odds ratio [OR] 1.54, p < 0.001). The use of VAD was associated with significant relative risk reduction (OR 0.43, p < 0.001) in waitlist adverse events among all patients, with relative risk reduction that overall did not vary by blood group. Among VAD recipients, waitlist adverse events were similar across all blood types. Among listed patients, there is a significantly higher adverse event rate in group O patients compared with others, irrespective of VAD use. With implantation of continuous flow HeartMate II or HeartWare VAD, all blood groups experience similar relative benefit and similar rates of adverse events. All patients, but particularly those with blood group O, eligible for VAD as a bridge to transplant should be considered for VAD placement.

The Use of Eptifibatide Alone or in Combination With Heparin or Argatroban for Suspected Thrombosis in Patients With Left Ventricular Assist Devices.

Pump thrombosis and hemolysis in patients with left ventricular assist devices (LVADs) are associated with significant morbidity and mortality. Intensification of anticoagulation has been suggested as potential therapy, with mixed results. The aim of this study is to assess the safety and efficacy of adding eptifibatide with or without an anticoagulation agent in managing patients with LVAD presenting with hemolysis and suspected pump thrombosis. This retrospective single center study included all patients who presented with their first episode of suspected pump thrombosis and were treated with eptifibatide with or without an anticoagulant between March 1, 2011 and July 30, 2015. A total of 27 patients (23 HeartMate II, 4 HeartWare) were identified. The average age was 55 years (range 19-75) and time from implant to event averaged 513 days (range 35-1760). The average lactate dehydrogenase on presentation was 1111 and 63% of patients had power elevations. The average international normalized ratio (INR) on admission was 2.4, with INR of ≥2 in 21/27 patients. All patients received eptifibatide: 10 received eptifibatide only, 9 received eptifibatide and argatroban, and 8 received eptifibatide and heparin. Warfarin was continued in 25/27 patients. Overall, 21 patients (77.8%) were successfully treated medically, 5 (18.5%) underwent pump exchange, and 1 (3.7%) died. There were no differences in outcomes or complications between the three treatment groups. Despite initial success, 12/21 patients developed repeat episodes of hemolysis at 1 year. The 1-year survival in the patients treated medically was 90% and surgically was 60%. Our experience indicates that medical therapy for hemolysis and suspected LVAD thrombosis with warfarin and eptifibatide alone or in combination with argatroban or heparin appears safe and may be effective, although the episodes of recurrent hemolysis after medical management remain high.

Utility of Head CT Scan for Acute Inpatient Delirium.

 Delirium is a common occurrence in hospitalized patients, especially in the geriatric age group. Data was retrospectively reviewed for patients who developed delirium during hospitalization. Acute intracranial changes on imaging were noted only in four patients (11%) and all had preimaging clinical symptoms and signs, which warranted imaging. Imaging should be considered only in the presence of head injury, fall, history of anticoagulation, focal neurological signs, fever, and raised intracranial pressure. Development of more clear guidelines will result in decreased ordering of unnecessary neuroimaging, substantial cost savings, and less radiation exposure for patients.

Prevalence of heart failure signs and symptoms in a large primary care population identified through the use of text and data mining of the electronic health record.

BACKGROUND: The electronic health record (EHR) contains a tremendous amount of data that if appropriately detected can lead to earlier identification of disease states such as heart failure (HF). Using a novel text and data analytic tool we explored the longitudinal EHR of over 50,000 primary care patients to identify the documentation of the signs and symptoms of HF in the years preceding its diagnosis. METHODS AND RESULTS: Retrospective analysis consisted of 4,644 incident HF cases and 45,981 group-matched control subjects. Documentation of Framingham HF signs and symptoms within encounter notes were carried out with the use of a previously validated natural language processing procedure. A total of 892,805 affirmed criteria were documented over an average observation period of 3.4 years. Among eventual HF cases, 85% had ≥1 criterion within 1 year before their HF diagnosis, as did 55% of control subjects. Substantial variability in the prevalence of individual signs and symptoms were found in both case and control subjects. CONCLUSIONS: HF signs and symptoms are frequently documented in a primary care population as identified through automated text and data mining of EHRs. Their frequent identification demonstrates the rich data available within EHRs that will allow for future work on automated criterion identification to help develop predictive models for HF.

Compliance with the Adult Treatment Panel III guidelines for hyperlipidemia in a resident-run ambulatory clinic: a retrospective data analysis.

BACKGROUND: One in every six adults (16.3% of the U.S. adult population) has high total cholesterol levels, and they are at double the risk of heart disease compared with people with optimal levels. OBJECTIVE: To evaluate compliance of internal medicine residents with the latest National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) guidelines in treating patients with hyperlipidemia. DESIGN: Retrospective observational study. SETTING: Ambulatory Clinic, Saint Vincent Hospital, Worcester, Massachusetts. PATIENTS: Patients with a diagnosis of hyperlipidemia who attended the clinic during a 1-ear period, from December 2009 to November 2010. MEASUREMENTS: A review of medical records was conducted to evaluate residents' compliance with the NCEP-ATP III guidelines for LDL cholesterol and non-HDL cholesterol management. RESULTS: Seven hundred seventy charts were reviewed. Only 212 (27.5%) met the inclusion criteria. Analysis of data revealed better compliance with drug therapy (44%-77%) and therapeutic lifestyle changes (44%-83%) when compared with follow-up recommendations (22%-31%). An increase in compliance also was noted in all areas of intervention when patients had an abnormal lipid profile. LIMITATIONS: Compliance was assessed on the basis of electronic medical record documentation alone and hence we may be underestimating compliance with therapeutic lifestyle changes and follow-up recommendations. CONCLUSION: Compliance among internal medicine residents in the diagnosis, treatment and follow-up of patients with hyperlipidemia according to NCEP-ATP III guidelines was suboptimal and needs improvement.

Fatal Enterococcus durans aortic valve endocarditis: a case report and review of the literature.

Most enterococcal endocarditis is caused by Enterococcus faecalis and Enterococcus faecium. Enterococcus durans is a rare member of non-faecalis, non-faecium enterococcal species and is found in the intestines of animals. E durans endocarditis is a very rare infection-only two cases of endocarditis in humans have been reported in the literature-and usually associated with good outcomes when treated with appropriate antibiotics. We report the first case of fatal E durans endocarditis. This patient had end-stage liver disease with associated compromised immune status that likely contributed to the progression of disease in spite of appropriate antibiotic coverage and clearance of bacteraemia.

Usefulness of diastolic time measured on electrocardiogram to improve sensitivity and specificity of exercise tolerance tests.

The current exercise tolerance test (ETT) criteria predominantly assess changes in ST-segment deviation (i.e., a systolic component of the cardiac cycle). Because diastolic dysfunction precedes that of systolic dysfunction during myocardial ischemia and most coronary flow is diastolic, the addition of electrocardiographic markers of diastolic time might improve the ETT sensitivity and specificity for detecting significant coronary artery disease. Among consecutive patients who had an ETT and subsequently underwent coronary angiography, we evaluated the diastolic time by assessing the TP and TQ segments and TP/RR and TQ/RR ratios in each ETT stage. Coronary artery disease was defined angiographically as significant (≥70% lumen occlusion), intermediate (>50% but <70% lumen occlusion), or nonsignificant (≤50% lumen occlusion). Of the 48 study patients, hypertension and hyperlipidemia appeared highly prevalent. TP, TQ, TP/RR, and TQ/RR correlated significantly with RR and changed with each ETT stage. Although TP and TQ were not significantly associated with significant coronary artery disease, TP/RR and TQ/RR proved to be, particularly beyond stage 2. When TQ/RR of ≤0.39 and TP/RR of ≤0.13 were used, their individual sensitivities and specificities were reasonably comparable to that of traditional ETT criteria (79% sensitivity and 44% specificity at our institution). Adding TQ/RR of ≤0.39 and/or TP/RR of ≤0.13 to existing ETT criteria improved its sensitivity to 100% and specificity to 86%. In conclusion, the addition of diastolic time indexes of TP/RR and TQ/RR significantly improved the overall ETT diagnostic value above the guideline-oriented, perhaps "traditional," criteria for the diagnosis of myocardial ischemia. Such parameters should be widely investigated further for clinical accuracy and compatibility.

Resistant thrombocytopenia in an HIV and hepatitis C patient: treatment response with novel agent eltrombopag.

HIV-associated thrombocytopenia is a disease which can be recurrent to standard therapy which includes highly active antiretroviral therapy (HAART) therapy, steroids and immunoglobulin. We report a patient with HIV and hepatitis C who presented with resistant thrombocytopenia. Treatment with Eltrombopag - a thrombopoeitin receptor agonist showed initial good response with recurrence of thrombocytopenia. This novel agent could be considered as a treatment option prior to splenectomy and may be useful as a temporizing measure.

Acute renal failure, thrombocytopenia, and elevated liver enzymes after concurrent abuse of alcohol and cocaine.

Cocaine has been associated with known adverse effects on cardiac, cerebrovascular and pulmonary systems. However, the effect of cocaine on other organs has not been extensively reported. A middle age man presented with abdominal pain and nausea after inhalation of crack cocaine. On admission, he was found to be hypertensive and tachycardic. Physical examination revealed mild abdominal tenderness without rebound. Laboratory investigations were significant for acute kidney failure with elevated serum creatinine (3.72 mg/dL), thrombocytopenia (platelet count 74,000/UL), elevated alanine and aspartate transaminases (ALT 331 U/L; AST 462 U/L) and elevated creatine phosphokinase (CPK 5885 U/L). Urine toxicology screening solely revealed cocaine. A clinical diagnosis of cocaine toxicity was made and patient was admitted to the intensive care unit because of multi organ failure. Despite downward trending of liver enzymes during the hospital course, he continued to have residual renal insufficiency and a low platelet count at the time of discharge. In a patient with history of recent cocaine use presenting with these manifestations, cocaine itself should be considered as a likely cause.

Recurrent tense pneumoperitoneum due to air influx via abdominal wall stoma of a PEG tube.

A 70 years old male on ventilatory and circulatory support for sepsis and non ST segment elevation myocardial infarction developed abdominal distension 14 d after placement of a percutaneous endoscopic gastrostomy tube for enteral feeding. Radiography revealed free air in the abdomen and gastrograffin (G) study showed no extravasation into the peritoneum. The G tube was successfully repositioned with mechanical release of air. Imaging showed complete elimination of free air but the patient had a recurrence of pneumoperitoneum. Mechanical release of air with sealing of the abdominal wound was performed. Later, the patient was restarted on tube feeding with no complications. This case demonstrates a late complication of pneumoperitoneum with air leakage from the abdominal wall stoma.

Irradiation toxic effects during intra-arterial chemotherapy for retinoblastoma: should we be concerned?

OBJECTIVE: To evaluate irradiation toxic effects from fluoroscopy during intra-arterial chemotherapy for retinoblastoma. DESIGN: Prospective trial. PARTICIPANTS: Eight patients treated with intra-arterial chemotherapy. MAIN OUTCOME MEASURES: Irradiation toxic effects in vital organs. RESULTS: The mean patient age was 29 months (range, 10-74 months) and 63% were male. The mean irradiation dose to the skin of the affected eye was 0.19173 Gy, to the contralateral eye was 0.03533 Gy, to the chest wall was 0.00296 Gy, and to the abdominal wall was 0.00104 Gy. The estimated irradiation dose to the lens in the treatment eye was 0.16 Gy, which, in accumulated doses, could be cataractogenic. The estimated irradiation dose from a single fluoroscopy session to other organs, including the brain (0.05560 Gy), thyroid (0.00192 Gy), bone marrow (0.00059 Gy), and gonads (0.00015 Gy), was far lower than the minimal toxic level. CONCLUSIONS: Careful use of fluoroscopy during intra-arterial chemotherapy with limited irradiation exposure is advised. Accumulated irradiation toxic effects following multiple sessions of intra-arterial chemotherapy could be cataractogenic and possibly carcinogenic, especially in irradiation-sensitive patients with retinoblastoma.

Successful treatment of thyroid storm with plasmapheresis in a patient with methimazole-induced agranulocytosis.

OBJECTIVE: To report a case of a patient with Graves disease presenting with agranulocytosis induced by methimazole, with subsequent thyroid storm and successful therapeutic use of plasmapheresis. METHODS: The clinical features and laboratory findings in a patient with agranulocytosis and thyroid storm are presented, and the available literature on utilization of plasmapheresis in the setting of thyrotoxicosis is reviewed. RESULTS: A 40-year-old Vietnamese woman with Graves disease was admitted with methimazole-induced agranulocytosis. Treatment with methimazole was discontinued, and therapy with antibiotics, granulocyte colony-stimulating factor, and ibuprofen was initiated. During hospitalization of the patient, her clinical status deteriorated, with development of pericarditis, thrombocytopenia, and thyroid storm. Treatment with plasmapheresis yielded near-euthyroidism in 3 days. Subsequently, she underwent successful total thyroidectomy. CONCLUSION: Our case highlights the effectiveness of plasmapheresis when clinical situations prohibit the use of traditional treatment methods for thyrotoxicosis or thyroid storm (or both).

In silico structure-based design of a novel class of potent and selective small peptide inhibitor of Mycobacterium tuberculosis Dihydrofolate reductase, a potential target for anti-TB drug discovery.

The worldwide TB structural genomics initiative has identified several new drug targets for Mycobacterium tuberculosis (M. tb). Dihydrofolate reductase (DHFR) catalyzes the NADPH-dependent reduction of dihydrofolate to tetrahydrofolate that is essential for DNA synthesis. Inhibition of its activity leads to arrest of DNA synthesis and hence cell death. Thus, M. tb DHFR (mtDHFR) is an attractive novel drug target for developing anti-TB drugs. Structural comparison of mtDHFR and human DHFR (hDHFR) reveals key differences in the active sites. These differences can be exploited for the design of selective inhibitors for mtDHFR. Based on the recently determined high resolution crystal structure of mtDHFR complexed with known inhibitor methotrexate (MTX) and cofactor NADPH, a tri-peptide inhibitor has been identified using a structure-based drug design approach. Docking studies indicate that the designed tripeptide inhibitor has a high potency (K (d) = 1.78 nM) and is a selective (approximately 120 fold over hDHFR) inhibitor for mtDHFR. Hence, the tripeptide is a suitable lead compound for the development of novel anti-TB drugs.

Structure-based design of a novel class of potent inhibitors of InhA, the enoyl acyl carrier protein reductase from Mycobacterium tuberculosis: a computer modelling approach.

The NADH-dependent Enoyl-ACP reductase (InhA) of Mycobacterium tuberculosis has been shown to be the primary target of the frontline drug isoniazid (INH). However, INH must be first activated by katG gene, mutations in which have mediated resistance to INH. Recently, direct inhibitors of InhA have been reported. Using a structure-based approach, we have identified a tripeptide inhibitor with the sequence WYW, which is 100 times more potent than the existing inhibitors. It is therefore, a potential lead compound for the development of new anti-TB drugs.