Incidental finding of a left atrial thrombus during surgical management of a massive pulmonary embolism.

A 58-year-old male presented with a hemodynamically significant pulmonary embolism. Computed tomography angiogram revealed a saddle embolus in the main pulmonary artery with extensive clot burden affecting all lobes and right heart strain. Transthoracic echocardiogram displayed a dilated right ventricle with reduced systolic function. The patient was scheduled for pulmonary embolectomy. The intraoperative transesophageal echocardiogram (TEE) demonstrated a mobile left atrial thrombus that was missed on previous imaging. After removal of the thrombi, TEE showed a patent foramen ovale (PFO). The left atrial thrombus passed across the PFO secondary to increased right heart and pulmonary pressures.

Ethanol Lock Therapy Markedly Reduces Catheter-Related Blood Stream Infections in Adults Requiring Home Parenteral Nutrition: A Retrospective Study From a Tertiary Medical Center.

BACKGROUND: The use of central venous catheter (CVC) access for home parenteral nutrition (HPN) is associated with catheter-related bloodstream infections (CRBSIs). There are limited data on the use of ethanol lock therapy (ELT) to prevent CRBSI in adult HPN patients. Our aim was to determine whether the routine institution of ELT decreased the incidence of CRBSI compared with historic controls at Emory University Hospital (EUH) in Atlanta, Georgia, USA. METHODS: EUH medical records of adult HPN patients discharged with a tunneled, silicone CVC on ELT were retrospectively studied during a pre-hoc determined 14-month observation period (n = 87; 13,386 catheter days) and compared with clinically similar HPN patients from the same institution before institution of the ELT protocol for all appropriate patients. The ELT protocol involved instilling 2 mL of 70% ethanol into each catheter lumen daily after the HPN cycle, following initial flushing with normal saline. RESULTS: Only 5 of 87 patients (5.7%) who received ELT were diagnosed with a CRBSI (0.45/1000 catheter days) during observation. We compared these data with our previously published clinically matched patient population from EUH (n = 22) receiving HPN via a silicone CVC without ELT. Of these historical controls, 45.5% were diagnosed with 1 or more CRBSIs (8.7/1000 catheter days) during observation (P < .001 vs the current ELT cohort). CONCLUSIONS: In this retrospective study with historical controls from the same academic center, institution of ELT in adults requiring HPN via a silicone CVC was associated with a marked (19-fold) reduction in CRBSI.

Thiamin Status in Adults Receiving Chronic Diuretic Therapy Prior to Admission to a Medical Intensive Care Unit: A Pilot Study.

BACKGROUND: The aim of the study was to determine serum thiamin concentrations in critically ill medical patients who required chronic diuretic drug treatment before admission to a medical intensive care unit (ICU). METHODS: This prospective study was performed in a medical ICU. Subjects who received diuretic drug therapy for at least 6 months prior to ICU admission constituted the diuretic group. The control group was clinically matched adults admitted to the same ICU but without a history of diuretic therapy. RESULTS: A total of 50 subjects were included (25 subjects in each of the diuretic and control groups). In the diuretic group, daily dose of furosemide prior to admission was 40 mg/d (range of 20-160 mg/d). In all subjects, the ICU admission baseline blood thiamin concentrations were 31.2 ± 27.1 ng/mL. In the diuretic group, the baseline whole blood thiamin level was significantly lower compared with levels in the control group (15.5 ± 10.7 vs 46.8 ± 29.5 ng/mL; P < 0.001). On day 2 after entry, thiamin levels remained low (23.2 ± 15.4 ng/mL in the diuretic group vs 49 ± 38 ng/mL in the control group; P = 0.003). Low thiamin levels were found in 96% of patients at baseline and in 72% of patients on the second day in the diuretic group. CONCLUSION: Adults receiving chronic diuretic therapy and then requiring medical ICU care commonly exhibit thiamin depletion on admission to the ICU and during the initial days of ICU care.

Micronutrient Alterations During Continuous Renal Replacement Therapy in Critically Ill Adults: A Retrospective Study.

BACKGROUND: Continuous renal replacement therapy (CRRT) is commonly used to provide renal replacement therapy in the intensive care unit. Limited published data suggest that CRRT may lead to depletion of water-soluble vitamins and trace elements. The goal of this study was to identify the incidence of trace element and vitamin deficiencies in critically ill patients during CRRT. MATERIALS AND METHODS: This study is based on a retrospective chart review of patients who were referred to Emory University Hospital's nutrition support services and had at least 1 serum micronutrient level measured during CRRT (thiamin, pyridoxine, ascorbic acid, folate, zinc, and copper) between April 1, 2009, and June 1, 2012. RESULTS: Seventy-five patients were included in the study. Nine of 56 patients (16%) had below-normal whole blood thiamin concentrations, and 38 of 57 patients (67%) had below-normal serum pyridoxine levels. Serum ascorbic acid and folate deficiencies were identified among 87% (13 of 15) and 33% (3 of 9) of the study patients, respectively. Nine of 24 patients had zinc deficiency (38%), and 41 of 68 patients had copper deficiency (60%). Of the 75 total subjects, 60 patients (80%) had below-normal levels of at least 1 of the micronutrients measured. CONCLUSIONS: The incidence of various micronutrient deficiencies in critically ill patients who required CRRT was higher than previously reported. Prospective studies are needed to determine the impact of CRRT on micronutrient status and the potential clinical and metabolic efficacy of supplementation in the intensive care unit setting.

Efficacy and Safety of Glutamine-supplemented Parenteral Nutrition in Surgical ICU Patients: An American Multicenter Randomized Controlled Trial.

OBJECTIVE: To determine whether glutamine (GLN)-supplemented parenteral nutrition (PN) improves clinical outcomes in surgical intensive care unit (SICU) patients. SUMMARY BACKGROUND DATA: GLN requirements may increase with critical illness. GLN-supplemented PN may improve clinical outcomes in SICU patients. METHODS: A parallel-group, multicenter, double-blind, randomized, controlled clinical trial in 150 adults after gastrointestinal, vascular, or cardiac surgery requiring PN and SICU care. Patients were without significant renal or hepatic failure or shock at entry. All received isonitrogenous, isocaloric PN [1.5 g/kg/d amino acids (AAs) and energy at 1.3× estimated basal energy expenditure]. Controls (n = 75) received standard GLN-free PN (STD-PN); the GLN group (n = 75) received PN containing alanyl-GLN dipeptide (0.5 g/kg/d), proportionally replacing AA in PN (GLN-PN). Enteral nutrition (EN) was advanced and PN weaned as indicated. Hospital mortality and infections were primary endpoints. RESULTS: Baseline characteristics, days on study PN and daily macronutrient intakes via PN and EN, were similar between groups. There were 11 hospital deaths (14.7%) in the GLN-PN group and 13 deaths in the STD-PN group (17.3%; difference, -2.6%; 95% confidence interval, -14.6% to 9.3%; P = 0.66). The 6-month cumulative mortality was 31.4% in the GLN-PN group and 29.7% in the STD-PN group (P = 0.88). Incident bloodstream infection rate was 9.6 and 8.4 per 1000 hospital days in the GLN-PN and STD-PN groups, respectively (P = 0.73). Other clinical outcomes and adverse events were similar. CONCLUSIONS: PN supplemented with GLN dipeptide was safe, but did not alter clinical outcomes among SICU patients.

Characterization of post-hospital infections in adults requiring home parenteral nutrition.

OBJECTIVE: Limited data are available on the incidence and risk factors for infection in patients requiring home parenteral nutrition (HPN). METHODS: A retrospective study was conducted in 101 consecutive adults (63 female, 38 male) discharged on HPN from the Emory University Hospital, Atlanta, GA. New bloodstream infections (BSIs) requiring rehospitalization and other infections were evaluated. RESULTS: Most infections (75%) developed during the initial 6 mo after hospital discharge; rates of BSI were particularly high during the first 4 mo. Fifty-six patients (55.4%) developed 102 BSIs (11.5 BSIs/1000 catheter-days). Most BSIs were attributed to gram-positive organisms (46%), including coagulase-negative Staphylococcus, Staphylococcus aureus, Enterococcus species, and others, followed by Candida species (20%) and gram-negative organisms (13%). Twenty-one percent of BSIs were polymicrobial. The BSI incidence rate ratio was significantly increased for patients with mean prehospital discharge blood glucose concentrations in the highest quartile versus the lowest quartile (incidence rate ratio 2.4, P = 0.017). Patients with a peripherally inserted central catheter versus non-peripherally inserted central catheter central venous catheters had significantly higher rates of BSI (P = 0.018). Thirty-nine patients (38.6%) developed 81 non-BSIs, including pneumonia, urinary tract infections, and surgical site infections. Postdischarge PN dextrose, lipid, and total calorie doses were unrelated to BSI but were variably related to the rate of non-BSIs. CONCLUSIONS: Adult patients on HPN exhibit a very high incidence of post-hospital infections. Higher mean blood glucose levels during predischarge hospitalization and the use of peripherally inserted central catheters at discharge are associated with an increased risk of BSI in the postdischarge home setting.

Efficacy of parenteral nutrition supplemented with glutamine dipeptide to decrease hospital infections in critically ill surgical patients.

BACKGROUND: Nosocomial infections are an important cause of morbidity and mortality in the surgical intensive care unit (SICU). Clinical benefits of glutamine-supplemented parenteral nutrition may occur in hospitalized surgical patients, but efficacy data in different surgical subgroups are lacking. The objective was to determine whether glutamine-supplemented parenteral nutrition differentially affects nosocomial infection rates in selected subgroups of SICU patients. METHODS: This was a double-blind, randomized, controlled study of alanyl-glutamine dipeptide-supplemented parenteral nutrition in SICU patients requiring parenteral nutrition and SICU care after surgery for pancreatic necrosis, cardiac, vascular, or colonic surgery. Subjects (n = 59) received isocaloric/isonitrogenous parenteral nutrition, providing 1.5 g/kg/d standard glutamine-free amino acids (STD-PN) or 1.0 g/kg/d standard amino acids + 0.5 g/kg/d glutamine dipeptide (GLN-PN). Enteral feedings were advanced as tolerated. Nosocomial infections were determined until hospital discharge. RESULTS: Baseline clinical/metabolic data were similar between groups. Plasma glutamine concentrations were low in all groups and were increased by GLN-PN. GLN-PN did not alter infection rates after pancreatic necrosis surgery (17 STD-PN and 15 GLN-PN patients). In nonpancreatic surgery patients (12 STD-PN and 15 GLN-PN), GLN-PN was associated with significantly decreased total nosocomial infections (STD-PN 36 vs GLN-PN 13, P < .030), bloodstream infections (7 vs 0, P < .01), pneumonias (16 vs 6, P < .05), and infections attributed to Staphylococcus aureus (P < .01), fungi, and enteric Gram-negative bacteria (each P < .05). CONCLUSIONS: Glutamine dipeptide-supplemented parenteral nutrition did not alter infection rates following pancreatic necrosis surgery but significantly decreased infections in SICU patients after cardiac, vascular, and colonic surgery.

Clinical and biological activity of soy protein powder supplementation in healthy male volunteers.

PURPOSE: To determine if a commonly used soy protein supplement exhibits biological activity in vivo and in vitro, we evaluated an over-the-counter soy protein powder supplement using blood from healthy male volunteers and in an estrogen receptor in vitro assay. SUBJECTS AND METHODS: We recruited healthy male volunteers 18 years of age or older that were in good health. Treatment consisted of consuming two scoops (56 g) of pure soy protein powder (Puritan's Pride, Oakdale, NY) daily for 28 days. Serum testosterone and luteinizing hormone (LH) levels were collected on days -7, 0, 14, and 28 of therapy, and day 42. A reporter estrogen receptor (ER) assay was used to determine the effect on ER-beta and ER-alpha in vitro. RESULTS: Twelve subjects were enrolled with a mean age of 32.25 years (range 25 to 47). Serum testosterone decreased 19%(+/-22%) during the 4-week use of soy protein powder (P = 0.021) and increased within 2 weeks after we discontinued soy protein powder. Serum LH concentrations decreased during the 4-week use of soy protein powder then increased within 2 weeks after we stopped the soy protein powder, but the changes did not reach statistical significance (P = 0.20). Soy protein powder was found to induce agonist activity to ER-beta using a reporter estrogen receptor assay in yeast. CONCLUSION: Soy protein powder decreases serum testosterone levels in healthy men and acts as an ER-beta agonist; the significance of this biological effect with respect to cancer prevention needs further study.

Lack of effect of moderate hepatic impairment on the pharmacokinetics of oral oseltamivir and its metabolite oseltamivir carboxylate.

AIMS: To compare the pharmacokinetics of oseltamivir and oseltamivir carboxylate in hepatically impaired patients and healthy subjects. METHODS: Hepatically impaired patients (n = 11) and healthy subjects (n = 11) were individually paired on the basis of gender, age (+/-10 years) and body weight (+/-20%) and administered a single dose of oseltamivir (75 mg). RESULTS: Oseltamivir and oseltamivir carboxylate C(max) were < or =6% and < or =19% lower, and their AUC(0,infinity) 33% higher and < or =19% lower, respectively, in hepatically impaired patients compared with healthy subjects. These changes are within the safety limits for the drug. CONCLUSIONS: The metabolism of oseltamivir is not compromised [corrected] in hepatically impaired patients. No dose adjustment is required in these patients when receiving oseltamivir.

A phase II trial of docetaxel and vinorelbine in patients with hormone-refractory prostate cancer.

Recent studies of docetaxel have demonstrated improved survival over mitoxantrone and prednisone in patients with hormone-refractory prostate cancer (HRPC), supporting the study of novel docetaxel-containing regimens as primary therapy or following initial docetaxel-based therapy. To evaluate the combination of docetaxel and vinorelbine in the treatment of patients with HRPC, 40 patients with proven adenocarcinoma of the prostate with progressive metastatic disease despite androgen ablation were enrolled onto this phase II trial. Patients were treated with docetaxel 60 mg/m2 on day 1 and vinorelbine 15 mg/m2 on days 1 and 8 of a 21-day cycle. All patients received dexamethasone 8 mg twice daily for 4 days starting 1 day prior to the docetaxel infusion. After the first three patients were enrolled, filgrastim was added on days 2-6 and 9-13. Of the 40 patients enrolled, 19 had no prior chemotherapy and 21 had received at least one prior chemotherapy regimen. Of the 19 patients without prior chemotherapy and the 21 with prior chemotherapy, 7 (37%) and 6 (29%) , respectively, demonstrated a decrease in prostate specific antigen by > 50% maintained for at least 4 weeks. Out of eight patients with measurable disease, one achieved a partial response and four demonstrated stable disease. There was one patient with deep vein thrombosis, and febrile neutropenia was noted in only three patients after the protocol was modified to include filgrastim support. The combination of docetaxel and vinorelbine with filgrastim was well tolerated and active against HRPC in patients with or without prior chemotherapy.

A phase II trial of imatinib mesylate in patients with prostate specific antigen progression after local therapy for prostate cancer.

PURPOSE: To test the hypothesis that progression of androgen sensitive prostate cancer is dependent on growth factors, such as platelet derived growth factor (PDGF), and inhibition of PDGF receptor (PDGF-R) with imatinib will induce anti-tumor activity. PATIENTS AND METHODS: This phase II study evaluated imatinib in patients with androgen sensitive prostate cancer and prostate specific antigen (PSA) progression after local therapy. Patients received 400 mg of imatinib orally twice a day for 24 weeks (six cycles). Patients were monitored every 4 weeks for an effect on PSA and toxicity. Immunohistochemistry (IHC) for PDGF-R was performed in available tumor specimens. RESULTS: Twenty-one patients were enrolled on this trial with a median age of 64 years. A total of 72 cycles of therapy were administered. Sixteen patients were evaluable for a response. Nine of the 16 patients demonstrated a stable PSA. Seven patients demonstrated PSA progression. Grade 3 and 4 toxicity included rash (4.1%), hematuria (1.4%), diarrhea (1.4%), and neutropenia (2.7%). Testosterone levels did not change during therapy. Four patients with available tumor demonstrated PDGF-R alpha and beta by IHC. CONCLUSIONS: This first study evaluated the efficacy and safety of imatinib in patients with early androgen sensitive prostate cancer following local therapy. As a single agent at this dosing, imatinib had limited biochemical activity.

Drug-related dyslipidemia after renal transplantation.

PURPOSE: The frequency, onset, mechanisms, and causes of dyslipidemia after renal transplantation are reviewed in the context of the adverse impact of lipid alterations, recent guidelines, and the available treatment options. SUMMARY: At least 60% of adult renal transplant recipients develop dyslipidemia, which occurs within one month of the initiation of immunosuppressive therapy and continues indefinitely unless treated. Cyclosporine, sirolimus, and prednisone are mainly implicated, and the lipid profile differs between individual agents. In recognition that lipid alterations in these patients are linked with development of ischemic heart disease, vascular mortality, and graft deterioration, the National Kidney Foundation has recently released guidelines suggesting a low-density-lipoprotein (LDL) cholesterol goal of < 100 mg/dL for these patients. Statins and diet therapy are recommended as first-line agents for achieving goal LDL cholesterol levels in this population. Recent evidence proved a reduction in adverse cardiovascular events when fluvastatin was utilized in one large-scale trial. Care should be taken with aggressive dosage adjustment because of the potential for a pharmacokinetic interaction with cyclosporine and a resultant increase in the risk of myopathy or rhabdomyolysis. Other options for improving the lipid profile include modifications in the immunosuppressive regimen, the addition of other lipid-modifying agents, and using alternative lipid-modifying agents. CONCLUSION: Statins and diet therapy should be used as first-line treatments in renal transplant recipients with dyslipidemia. Other strategies, including modification of the immunosuppressive regimen, and the addition of other lipid-modifying agents, have also yielded positive results.

Bleeding and thrombosis in high-risk renal transplantation candidates using heparin.

BACKGROUND: Heparin can reduce the risk of renal artery/vein thrombosis in renal transplant patients with hypercoagulable states (HCS), but is associated with a high bleeding risk. Little is known about risk factors for this bleeding risk or the optimal anticoagulation target. OBJECTIVE: To determine factors associated with this bleeding risk and determine the optimal partial thromboplastin time (PTT) ratio. METHODS: We retrospectively reviewed medical records of consecutive adult renal transplant recipients administered heparin for perioperative renal thrombosis prevention (1998-2002). RESULTS: Twenty-eight (3.86%) of 725 consecutive renal transplant recipients received heparin to prevent renal thrombosis. Eighteen patients (64.3%) had clinically important bleeding (14 major bleeding). Patients with and without bleeding were similar in baseline demographic characteristics and overall mean PTT. Bleeding occurred at a mean PTT ratio of 2.5 +/- 1, higher than the overall mean in bleeders and nonbleeders (p = 0.001). Among postoperative characteristics, higher maximum PTT (p = 0.052) and prolonged surgical antibiotic prophylaxis (p = 0.053), particularly with cefotetan (p = 0.091), trended toward a significant association with bleeding. Two renal thrombotic episodes occurred, both at PTT ratios <1.5. A PTT ratio of 1.5-1.9 resulted in no thrombosis and < or = 4.2% bleeding. CONCLUSIONS: The benefits and risks of therapeutic heparin anticoagulation in renal transplant patients with HCSs were confirmed. Higher PTTs and cefotetan antibiotic surgical prophylaxis could contribute to bleeding. The optimal PTT ratio appeared to be 1.5-1.9 to prevent thrombosis and limit bleeding risk.