Faculty Bibliography

PURPOSE/OBJECTIVE:To compare the effectiveness of continuous infusion of hydrocortisone versus intermittent boluses in the resolution of septic shock. METHODS:A retrospective chart review was performed to investigate the effects of low-dose hydrocortisone continuous infusion (200 mg per day) versus intermittent boluses (50 mg every six hours) in septic shock patients who did not respond to fluid resuscitation and vasopressors. The primary outcome was time to resolution of shock, defined by time from the initiation of hydrocortisone to time of vasopressor withdrawal when mean arterial pressure was greater than 65 mm Hg. Hospital length of stay, intensive care unit (ICU) length of stay, 28-day all-cause in-hospital mortality, and hyperglycemia were secondary outcomes. RESULTS:= 0.04). CONCLUSION/CONCLUSIONS:There was no significant difference in time to resolution of septic shock between continuous infusion (200 mg per day) and intermittent boluses (50 mg every six hours) of hydrocortisone. There were also no statistically significant differences in overall hospital length of stay, ICU length of stay, and 28-day all-cause in-hospital mortality. However, there was a significant difference in the incidence of hyperglycemia between the two groups, with patients in the bolus group experiencing more hyperglycemia than those in the continuous infusion group.

PURPOSE:The goal of this pharmacokinetic (PK) study was to evaluate whether a single 2-g prophylactic dose of cefazolin given (IV) bolus provides effective protective cefazolin levels for prophylaxis against methicillin-sensitive S. aureus (MSSA), the primary skin pathogen in bariatric surgery. MATERIALS AND METHODS:Thirty-seven patients having gastric bypass or sleeve gastrectomy received cefazolin 2-g preoperative prophylaxis. Serum, subcutaneous adipose tissue, and deep peri-gastric adipose tissue specimens were collected at incision and before skin closure. Cefazolin concentrations in serum and adipose tissue were determined by high-performance liquid chromatography. RESULTS:Penetration of cefazolin, a water soluble antibiotic, into adipose tissue was only 6-8 % of simultaneous serum levels. However, cefazolin tissue concentrations in all adipose tissue specimens, exceeded mean MIC for MSSA. CONCLUSIONS:not dose-dependent. Extremely high-dosed cefazolin, i.e., 3 or 4 g is excessive and unnecessary for bariatric surgery prophylaxis. A single cefazolin 2 g preoperative dose also eliminates the need for intraoperative redosing at 4 h.

PURPOSE/OBJECTIVE:To characterize medical industry-based payments made to US-based interventional radiology (IR) physicians, identify trends in compensation, and compare their payment profile with those of other related specialties, including vascular surgery (VS) and interventional cardiology (IC). Payments made to orthopedic surgery (OS) physicians are reported as a historical control. MATERIALS AND METHODS/METHODS:For each group, the total payment number, amount, and mean and median numbers and amounts were calculated. The data were then reanalyzed after correcting for statistical outliers. For IR, VS, and IC, leading industry sponsors, payment amount, and differences in payments from 2013 to 2014 were highlighted. Payments to IR were grouped by category and geographic location. The Kruskal-Wallis test was used for statistical analysis. RESULTS:A total of $26,857,622 went to 1,831 IR physicians, representing 70.9% of active IR physicians, and the corrected mean payment was $597 ± 832.2 (standard deviation). The respective values were $18,861,041, 3,383, 80.6%, and $851.59 for VS; $32,008,213, 7,939, 78.6%, and $417.16 for IC; and $357,528,020, 21,829, 77.8%, and $598.48 for OS. OS had the largest number of payments (295,465 vs 24,246 for IR, 84,635 for VS, and 160,443 for IC) and greatest total payment amount. VS had a significantly higher corrected median payment amount ($463; P < .0001) than IR ($214) and IC ($99). Covidien and Sirtex Medical were the leading industry sponsors to IR, and 64.6% of IR payments were compensation for services other than consulting. There was no significant difference in median payment received per geographic region (P = .32). CONCLUSIONS:OS received the largest number and total payment amount, and VS received a significantly greater corrected median payment amount, versus IR and IC. As the Open Payments program continues to be implemented, it remains to be seen how this information will affect relationships among physicians, patients, and industry.

OBJECTIVES/OBJECTIVE:The purpose of this study was to determine if implantation of multiple recalled defibrillator leads is associated with an increased risk of lead failure. BACKGROUND:The authors of the Pacemaker and Implantable Defibrillator Leads Survival Study ("PAIDLESS") have previously reported a relationship between recalled lead status, lead failure, and patient mortality. This substudy analyzes the relationship in a smaller subset of patients who received more than one recalled lead. The specific effects of having one or more recalled leads have not been previously examined. METHODS:This study analyzed lead failure and mortality of 3802 patients in PAIDLESS and compared outcomes with respect to the number of recalled leads received. PAIDLESS includes all patients at Winthrop University Hospital who underwent defibrillator lead implantation between February 1, 1996 and December 31, 2011. Patients with no recalled ICD leads, one recalled ICD lead, and two recalled ICD leads were compared using the Kaplan-Meier method and log-rank test. Sidak adjustment method was used to correct for multiple comparisons. All calculations were performed using SAS 9.4. P-values <.05 were considered statistically significant. RESULTS:This study included 4078 total ICD leads implanted during the trial period. There were 2400 leads (59%) in the no recalled leads category, 1620 leads (40%) in the one recalled lead category, and 58 leads (1%) in the two recalled leads category. No patient received more than two recalled leads. Of the leads categorized in the two recalled leads group, 12 experienced lead failures (21%), which was significantly higher (P<.001) than in the no recalled leads group (60 failures, 2.5%) and one recalled lead group (81 failures; 5%). Multivariable Cox's regression analysis found a total of six significant predictive variables for lead failure including the number of recalled leads (P<.001 for one and two recalled leads group). CONCLUSIONS:The number of recalled leads is highly predictive of lead failure. Lead-based multivariable Cox's regression analysis produced a total of six predictive variable categories for lead failure, one of which was the number of recalled leads. Kaplan-Meier analysis showed that the leads in the two recalled leads category failed faster than both the no recalled lead and one recalled lead groups. The greater the number of recalled leads to which patients are exposed, the greater the risk of lead failure.

Environmental enteropathy (EE) is a poorly understood condition that refers to chronic alterations in intestinal permeability, absorption, and inflammation, which mainly affects young children in resource-limited settings. Recently, EE has been linked to suboptimal oral vaccine responses in children, although immunological mechanisms are poorly defined. The objective of this study was to determine host factors associated with immune responses to an oral cholera vaccine (OCV). We measured antibody and memory T cell immune responses to cholera antigens, micronutrient markers in blood, and EE markers in blood and stool from 40 Bangladeshi children aged 3-14 years who received two doses of OCV given 14 days apart. EE markers included stool myeloperoxidase (MPO) and alpha anti-trypsin (AAT), and plasma endotoxin core antibody (EndoCab), intestinal fatty acid binding protein (i-FABP), and soluble CD14 (sCD14). We used multiple linear regression analysis with LASSO regularization to identify host factors, including EE markers, micronutrient (nutritional) status, age, and HAZ score, predictive for each response of interest. We found stool MPO to be positively associated with IgG antibody responses to the B subunit of cholera toxin (P = 0.03) and IgA responses to LPS (P = 0.02); plasma sCD14 to be positively associated with LPS IgG responses (P = 0.07); plasma i-FABP to be positively associated with LPS IgG responses (P = 0.01) and with memory T cell responses specific to cholera toxin (P = 0.01); stool AAT to be negatively associated with IL-10 (regulatory) T cell responses specific to cholera toxin (P = 0.02), and plasma EndoCab to be negatively associated with cholera toxin-specific memory T cell responses (P = 0.02). In summary, in a cohort of children 3-14 years old, we demonstrated that the majority of biomarkers of environmental enteropathy were positively associated with immune responses after vaccination with an OCV.

The purpose of this study was to determine the prognostic value of late gadolinium enhancement seen on cardiac magnetic resonance (CMR) imaging in patients with nonischemic cardiomyopathy (NICMP). Patients with NICMP are at increased risk for cardiovascular events and death. The presence of late gadolinium enhancement (LGE) in CMR may be associated with a poor prognosis, but its significance is still under investigation. We retrospectively studied 105 consecutive patients with NICMP and left ventricular ejection fraction (LVEF) ≤40% referred for CMR. The cohort was analyzed for the presence of LGE and left and right ventricular functional parameters. Patients were followed for the composite end point of hospitalization for congestive heart failure, appropriate implantable cardioverter-defibrillator therapy, or all-cause mortality. LGE was observed in 68% (n = 71) of the cohort. Both groups were similar in age, LVEF and LV end-diastolic volume. The LGE+ patients were more often men and had larger right ventricular volumes. At a mean follow-up of 806 ± 582 days, there were 26 patients (23 in the LGE+ group) who reached the primary end point. Event-free survival was significantly worse for the LGE+ patients. After adjusting for traditional risk factors (age, gender, and LVEF), patients with LGE had an increased risk of experiencing the primary end point (hazard ratio 4.47, 95% CIs 1.27 to 15.74, p = 0.02). The presence of LGE in patients with NICMP strongly predicts the occurrence of adverse events. In conclusion, this may be important in risk stratification and management.

Vitex doniana is an important African medicinal plant traditionally used for the treatment of many diseases including type 2 diabetes (T2D). In this study, ethyl acetate, ethanol and aqueous extracts of the stem bark, root and leaf of V. doniana were analyzed for in vitro anti-oxidative activity and the results indicated that the ethanolic extract of the leaves had the best anti-oxidative activity. Subsequently, the ethanolic extract of the leaves was partitioned between hexane, dichloromethane, ethyl acetate and water. The aqueous fraction had a significantly ( p < 0.05) higher phenolics content and also showed the best anti-oxidative activity within the fractions. Furthermore, the aqueous fraction demonstrated significantly (p < 0.05) more potent inhibitory activities against α-glucosidase and α-amylase than other fractions. Steady state kinetics analysis revealed that the aqueous fraction inhibited both (α-glucosidase and (α-amylase activities in a non-competitive manner with inhibition binding constant (Ki) values of 5.93 and 167.44 μg/mL, respectively. Analysis of the aqueous fraction by GC-MS showed the presence of resorcinol, 4-hydroxybenzoic acid, 3,4,5-trimethoxyphenol and 2,4'-dihydroxychalcone identified by their mass fragmentation patterns and comparison to standard spectra. The results obtained in this study showed that V doniana leaves have a good in vitro anti-T2D potential possibly elicited through phenolics.