No evidence of ongoing HIV replication or compartmentalization in tissues during combination antiretroviral therapy: Implications for HIV eradication.

HIV persistence during combination antiretroviral therapy (cART) is the principal obstacle to cure. Mechanisms responsible for persistence remain uncertain; infections may be maintained by persistence and clonal expansion of infected cells or by ongoing replication in anatomic locations with poor antiretroviral penetration. These mechanisms require different strategies for eradication, and determining their contributions to HIV persistence is essential. We used phylogenetic approaches to investigate, at the DNA level, HIV populations in blood, lymphoid, and other infected tissues obtained at colonoscopy or autopsy in individuals who were on cART for 8 to 16 years. We found no evidence of ongoing replication or compartmentalization of HIV; we did detect clonal expansion of infected cells that were present before cART. Long-term persistence, and not ongoing replication, is primarily responsible for maintaining HIV. HIV-infected cells present when cART is initiated represent the only identifiable source of persistence and is the appropriate focus for eradication.

The use of low-calorie sweeteners is associated with self-reported prior intent to lose weight in a representative sample of US adults.

BACKGROUND: Low-calorie sweeteners (LCSs) are said to be a risk factor for obesity and diabetes. Reverse causality may be an alternative explanation. METHODS: Data on LCS use, from a single 24-h dietary recall, for a representative sample of 22 231 adults were obtained from 5 cycles of the National Health and Nutrition Examination Survey (1999-2008 NHANES). Retrospective data on intent to lose or maintain weight during the prior 12-months and 10-year weight history were obtained from the weight history questionnaire. Objectively measured heights and weights were obtained from the examination. Primary analyses evaluated the association between intent to lose/maintain weight and use of LCSs and specific LCS product types using survey-weighted generalized linear models. We further evaluated whether body mass index (BMI) may mediate the association between weight loss intent and use of LCSs. The association between 10-year weight history and current LCS use was evaluated using restricted cubic splines. RESULTS: In cross-sectional analyses, LCS use was associated with a higher prevalence of obesity and diabetes. Adults who tried to lose weight during the previous 12 months were more likely to consume LCS beverages (prevalence ratio=1.64, 95% confidence interval (CI) 1.54-1.75), tabletop LCS (prevalence ratio=1.68, 95% CI 1.47-1.91) and LCS foods (prevalence ratio=1.93, 95% CI 1.60-2.33) as compared with those who did not. In mediation analyses, BMI only partially mediated the association between weight control history and the use of LCS beverages, tabletop LCS, but not LCS foods. Current LCS use was further associated with a history of prior weight change (for example, weight loss and gain). CONCLUSIONS: LCS use was associated with self-reported intent to lose weight during the previous 12 months. This association was only partially mediated by differences in BMI. Any inference of causality between attempts at weight control and LCS use is tempered by the cross-sectional nature of these data and retrospective self-reports of prior weight loss/maintenance intent.

Validating self-reported food expenditures against food store and eating-out receipts.

BACKGROUND/OBJECTIVES: To compare objective food store and eating-out receipts with self-reported household food expenditures. SUBJECTS/METHODS: The Seattle Obesity Study II was based on a representative sample of King County adults, Washington, USA. Self-reported household food expenditures were modeled on the Flexible Consumer Behavior Survey (FCBS) Module from 2007 to 2009 National Health and Nutrition Examination Survey (NHANES). Objective food expenditure data were collected using receipts. Self-reported food expenditures for 447 participants were compared with receipts using paired t-tests, Bland-Altman plots and κ-statistics. Bias by sociodemographics was also examined. RESULTS: Self-reported expenditures closely matched with objective receipt data. Paired t-tests showed no significant differences between receipts and self-reported data on total food expenditures, expenditures at food stores or eating out. However, the highest-income strata showed weaker agreement. Bland-Altman plots confirmed no significant bias across both methods-mean difference: 6.4; agreement limits: -123.5 to 143.4 for total food expenditures, mean difference 5.7 for food stores and mean difference 1.7 for eating out. The κ-statistics showed good agreement for each (κ 0.51, 0.41 and 0.49 respectively. Households with higher education and income had significantly more number of receipts and higher food expenditures. CONCLUSIONS: Self-reported food expenditures using NHANES questions, both for food stores and eating out, serve as a decent proxy for objective household food expenditures from receipts. This method should be used with caution among high-income populations, or with high food expenditures. This is the first validation of the FCBS food expenditures question using food store and eating-out receipts.

Socio-demographic correlates and trends in low-calorie sweetener use among adults in the United States from 1999 to 2008.

BACKGROUND/OBJECTIVES: Replacing added sugars in beverages and foods with low-calorie sweeteners (LCSs) is one strategy to reduce calories and manage body weight. There are few studies on LCS consumption by product category and by consumer socio-demographic status. SUBJECTS/METHODS: Data for a representative sample of 22 231 adults were obtained from five cycles of the National Health and Nutrition Examination Survey (1999-2008 NHANES). A single 24-h recall was used to identify consumers of LCS beverages, foods and tabletop sweeteners. Time-trend analyses were conducted for total LCS consumption and for LCS beverages. RESULTS: Approximately 30% of US adults consumed some type of LCS, with 19.5% consuming LCS beverages, 11.4% consuming tabletop LCS and 4.6% consuming LCS foods. LCS consumption by product category peaked at different ages, with older adults more likely to consume tabletop LCS and LCS foods. In age-adjusted analyses, LCS consumers in every product category were more likely to be women, 45-65 years old, non-Hispanic whites, US-born adults, college graduates and with higher household incomes. Predictors of LCS consumption were not altered upon adjustment for body mass index and diabetes status. LCS consumption from all sources and from LCS beverages increased between 1999 and 2008. CONCLUSIONS: LCS use was more common among populations with a lower burden of obesity and related chronic disease, specifically, non-Hispanic whites and those with more education/higher incomes. The reasons for this observed paradox are complex and merit additional research.

The relation of potassium and sodium intakes to diet cost among U.S. adults.

The 2010 Dietary Guidelines recommended that Americans increase potassium and decrease sodium intakes to reduce the burden of hypertension. One reason why so few Americans meet the recommended potassium or sodium goals may be perceived or actual food costs. This study explored the monetary costs associated with potassium and sodium intakes using national food prices and a representative sample of US adults. Dietary intake data from the 2001-2002 National Health and Nutrition Examination Survey were merged with a national food prices database. In a population of 4744 adults, the association between the energy-adjusted sodium and potassium intakes, and the sodium-to-potassium ratio (Na:K) and energy-adjusted diet cost was evaluated. Diets that were more potassium-rich or had lower Na:K ratios were associated with higher diet costs, while sodium intakes were not related to cost. The difference in diet cost between extreme quintiles of potassium intakes was $1.49 (95% confidence interval: 1.29, 1.69). A food-level analysis showed that beans, potatoes, coffee, milk, bananas, citrus juices and carrots are frequently consumed and low-cost sources of potassium. Based on existing dietary data and current American eating habits, a potassium-dense diet was associated with higher diet costs, while sodium was not. Price interventions may be an effective approach to improve potassium intakes and reduce the Na:K ratio of the diet. The present methods helped identify some alternative low-cost foods that were effective in increasing potassium intakes. The identification and promotion of lower-cost foods to help individuals meet targeted dietary recommendations could accompany future dietary guidelines.

The geographic distribution of obesity by census tract among 59 767 insured adults in King County, WA.

OBJECTIVE: To evaluate the geographic concentration of adult obesity prevalence by census tract (CT) in King County, WA, in relation to social and economic factors. METHODS AND DESIGN: Measured heights and weights from 59 767 adult men and women enrolled in the Group Health (GH) healthcare system were used to estimate obesity prevalence at the CT level. CT-level measures of socioeconomic status (SES) were median home values of owner-occupied housing units, percent of residents with a college degree and median household incomes, all drawn from the 2000 Census. Spatial regression models were used to assess the relation between CT-level obesity prevalence and socioeconomic variables. RESULTS: Smoothed CT obesity prevalence, obtained using an Empirical Bayes tool, ranged from 16.2-43.7% (a 2.7-fold difference). The spatial pattern of obesity was non-random, showing a concentration in south and southeast King County. In spatial regression models, CT-level home values and college education were more strongly associated with obesity than household incomes. For each additional $100 000 in median home values, CT obesity prevalence was 2.3% lower. The three SES factors together explained 70% of the variance in CT obesity prevalence after accounting for population density, race/ethnicity, age and spatial dependence. CONCLUSIONS: To our knowledge, this is the first report to show major social disparities in adult obesity prevalence at the CT scale that is based, moreover, on measured heights and weights. Analyses of data at sufficiently fine geographic scale are needed to guide targeted local interventions to stem the obesity epidemic.

Short-course raltegravir intensification does not reduce persistent low-level viremia in patients with HIV-1 suppression during receipt of combination antiretroviral therapy.

BACKGROUND: Combination antiretroviral therapy suppresses but does not eradicate human immunodeficiency virus type 1 (HIV-1) in infected persons, and low-level viremia can be detected despite years of suppressive antiretroviral therapy. Short-course (28-day) intensification of standard antiretroviral combination therapy is a useful approach to determine whether complete rounds of HIV-1 replication in rapidly cycling cells contribute to persistent viremia. We investigated whether intensification with the integrase inhibitor raltegravir decreases plasma HIV-1 RNA levels in patients receiving suppressive antiretroviral therapy. METHODS: Subjects (n = 10) with long-term HIV-1 suppression receiving combination antiretroviral regimens had their regimens intensified for 4 weeks with raltegravir. Plasma HIV-1 RNA level was determined before, during, and after the 4-week intensification period, using a sensitive assay (limit of detection, 0.2 copies of HIV-1 RNA/mL of plasma). A 4-week intensification course was chosen to investigate potential HIV-1 replication in cells with relatively short (approximately 1-14-day) half-lives. RESULTS: There was no evidence in any subject of a decline in HIV-1 RNA level during the period of raltegravir intensification or of rebound after discontinuation. Median levels of HIV-1 RNA before (0.17 log10 copies/mL), during (0.04 log10 copies/mL), and after (0.04 log10 copies/mL) raltegravir intensification were not significantly different (P > .1 for all comparisons in parametric analyses). High-performance liquid chromatography and mass spectroscopy experiments confirmed that therapeutic levels of raltegravir were achieved in plasma during intensification. CONCLUSIONS: Intensification of antiretroviral therapy with a potent HIV-1 integrase inhibitor did not decrease persistent viremia in subjects receiving suppressive regimens, indicating that rapidly cycling cells infected with HIV-1 were not present. Eradication of HIV-1 from infected persons will require new therapeutic approaches. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00618371.

Treatment intensification does not reduce residual HIV-1 viremia in patients on highly active antiretroviral therapy.

In HIV-1-infected individuals on currently recommended antiretroviral therapy (ART), viremia is reduced to <50 copies of HIV-1 RNA per milliliter, but low-level residual viremia appears to persist over the lifetimes of most infected individuals. There is controversy over whether the residual viremia results from ongoing cycles of viral replication. To address this question, we conducted 2 prospective studies to assess the effect of ART intensification with an additional potent drug on residual viremia in 9 HIV-1-infected individuals on successful ART. By using an HIV-1 RNA assay with single-copy sensitivity, we found that levels of viremia were not reduced by ART intensification with any of 3 different antiretroviral drugs (efavirenz, lopinavir/ritonavir, or atazanavir/ritonavir). The lack of response was not associated with the presence of drug-resistant virus or suboptimal drug concentrations. Our results suggest that residual viremia is not the product of ongoing, complete cycles of viral replication, but rather of virus output from stable reservoirs of infection.

Gene expression profiles in hepatitis C virus (HCV) and HIV coinfection: class prediction analyses before treatment predict the outcome of anti-HCV therapy among HIV-coinfected persons.

Therapy for hepatitis C virus (HCV) infection in human immunodeficiency virus (HIV)-infected patients results in modest cure rates. Gene expression patterns in peripheral blood mononuclear cells from 29 patients coinfected with HIV and HCV were used to predict virological response to therapy for HCV infection. Prediction analysis using pretherapy samples identified 79 genes that correctly classified all 10 patients who did not respond to therapy, 8 of 10 patients with a response at the end of treatment, and 7 of 9 patients with sustained virological response (86% overall). Analysis of 17 posttreatment samples identified 105 genes that correctly classified all 9 patients with response at the end of treatment and 7 of 8 patients with sustained virological response (94% overall). Failure of anti-HCV therapy was associated with elevated expression of interferon-stimulated genes. Gene expression patterns may provide a tool to predict anti-HCV therapeutic response.

[Correlation of MRI and histopathology of bone marrow in patients with multiple myeloma]. / Korrelation zwischen MRT und Histopathologie des Knochenmarks bei Patienten mit Multiplem Myelom.

PURPOSE: To compare MRI findings and histological plasmacellular infiltration of the bone marrow in patients with multiple myeloma (MM). MATERIAL AND METHODS: Twenty-four patients with different stages of MM underwent 1.5T MRI of the pelvic bone before iliac crest punch biopsy. Precontrast T1wSE and STIR and postcontrast (Gd-DTPA) T1wSE-fatsat were acquired using axial slices. Immediately after the biopsy, T1wSE was repeated to locate the biopsy canal. The corresponding region in the examination before punch biopsy was assessed for bone marrow involvement using a three-point score (0: negative, 1: suspect, 2: definite). RESULTS: Two patients were not included because the location of the biopsy canal was unclear. Of 7 patients without histological plasmacellular infiltration, MRI was false positive in one case (suspect). Of 15 patients with histological infiltration, MRI was positive in 10 cases (4 suspect, 6 definite). The T1wSE was positive in 9 cases, STIR in 8 cases, and postcontrast T1wSE-fatsat in 7 cases. In 10 of the 15 patients, the infiltration was histologically graded as low (5 - 20 % of bone marrow). In this group, MRI was only positive in 5 cases (3 suspect, 2 definite). Of five patients with the infiltration histologically graded as high (> 20 % of bone marrow), MRI was positive in all cases (1 suspect, 4 definite). CONCLUSION: Only advanced bone marrow infiltration in MM can be reliably detected by MRI. None of the used sequences proved to be significantly superior or inferior.

Assessment of gadobenate dimeglumine for magnetic resonance angiography: phase I studies.

RATIONALE AND OBJECTIVES: To assess the vascular contrasting properties of a new MR contrast agent (gadobenate dimeglumine [Gd-BOPTA]), which presents higher relaxivity because of reversible, weak protein interaction, and, to compare these properties with a standard gadolinium agent. MATERIALS AND METHODS: Two phase I trials compared intraindividually: (A) the vascular contrasting properties of Gd-BOPTA at three doses (0.0125, 0.05, and 0.2 mmol/kg body weight) and two flow rates (0.5 and 2.0 mL/s) in 10 volunteers; and (B) 0.1 mmol/kg body weight doses of Gd-BOPTA and Gd-DTPA at 2.0 mL/s using a modified magnetic resonance angiography (MRA) sequence with a temporal resolution of 1 s/f. Quantitative (ROI analysis) and fully blinded qualitative (reader review) assessment of images was performed. RESULTS: A dose of 0.2 mmol/kg resulted in higher maximum intensities, longer median peak widths, and larger areas under the curve than did the lower doses (0.0125 mmol/kg and 0.05 mmol/kg). In the intraindividual comparison, Gd-BOPTA demonstrated significantly better vascular enhancement characteristics in terms of signal peak duration (p < 0.05), maximum signal intensity (p < 0.05), and area under the enhancement curve (p < 0.01). The multireader assessment for overall vascular contrast preferred Gd-BOPTA at p < 0.03. CONCLUSIONS: Gd-BOPTA was shown to exhibit preferential and different vascular enhancement properties as compared with Gd-DTPA for MRA.

Bedside procedures. Solutions to the pitfalls of intrahospital transport.

The technology to perform diagnostic and therapeutic procedures at the bedside continues to advance. Because of documented hazards and the expense of intrahospital transport, the bedside is becoming an appealing site for procedures that are more commonly performed in radiologic, bronchoscopic, other procedural suites, and the operating room.

Bedside laparoscopy.

The improved technical sophistication of laparoscopy offers an attractive highly accurate diagnostic modality at the bedside for critically ill patients who are confined to the ICU and intensive monitoring unit and who are in need of timely abdominal evaluation. If the surgeon understands the physiologic effects of peritoneal insufflation and considers them during the procedure, the patient tolerates the procedure well. It is important to limit insufflation pressures and laparoscopy time. The author also recommends using the open Hasson technique. Its primary use is diagnostic in penetrating and blunt trauma and in the obscure abdomen. It has been successfully employed therapeutically for acalculous cholecystitis, abscess drainage, and correction of placement of gastrostomy tubes and peritoneal dialysis catheters. It helps avoid risky transport trips and negative or nontherapeutic laparotomy with its known associated risks.

Jejunostomy tube feedings should not be stopped in the perioperative patient.

BACKGROUND: Anesthetic standard of care is to restrict oral intake for 8 hours before elective surgery. There is no research addressing appropriate preoperative discontinuation of jejunostomy tube (J-tube) feedings. We hypothesized that patients could be fed safely, via a J-tube, until the time of surgery. METHODS: Patients admitted to a Level I Trauma Center, having J-tubes and undergoing a nonabdominal operation, were prospectively evaluated. Group I patients received J-tube feedings until transport to the operating room. Group II patients had tube feedings discontinued for at least 8 hours before surgery. Data were compared using the Student's t test and contingency table analysis. RESULTS: There were 46 patients in group I and 36 in group II. There was no incidence of aspiration. Patient groups did not differ in age, mortality, length of stay, injury severity score, or ventilator days. Group I patients had tube feedings discontinued for fewer hours before and after surgery than group II patients (before surgery: 1.40 +/- 1.20 vs 11.61 +/- 5.01, respectively; p < .001; after surgery: 2.99 +/- 7.49 vs 7.11 +/- 9.03, respectively; p = .043); received more kilocalories/ grams of protein on the day of surgery (group I vs group II, 1676.15/89.57 +/- 1133.21/38.04 vs 791.14/57.58 +/-498.66/79.87, respectively; p = .001/p = .032) and more kilocalories/grams of protein on the first postoperative day (group I vs group II, 1580.74/92.57 +/- 600.53/37.96 vs 1152.47/63.53 +/- 733.96/39.40, respectively; p = .006/p = .001). CONCLUSIONS: Patients receiving J-tubes who are undergoing nonabdominal operations may safely continue enteral nutrition at maximum protein and caloric intake until surgery.

Syncope as etiology of road crashes involving elderly drivers.

A significant number of elderly drivers present without discernible external cause for their road crash. We hypothesize that syncope may contribute to their crash etiology and prospectively evaluated drivers older than 60 years with unexplained crash, presenting to our trauma center during a 1-year period. Prehospital data and prior medical history were obtained on all, followed by a standard syncope work-up. Of 79 drivers ages 60-98, 58 (73%) were at fault in the crash. In 33 (57%), the crash etiology could not be determined. Thirteen had prior syncope history. Workup was negative in two patients, and six died or were transferred before evaluation. Twenty-five of 33 (76%) had positive workups for syncope: cardiac causes in 10; neurologic in seven; psychiatric in five, endocrine in two; one indeterminant. Ten of 18 who survived had license revocation for medical reasons. Syncopal episodes are a frequent contributor to unexplained crashes among elderly drivers and should be suspected whenever external causes are not apparent.

Morbidity of negative coeliotomy in trauma.

Exploratory coeliotomy is essential in the care of abdominal trauma, but negative operation has a reported morbidity rate as high as 18 per cent. Ancillary studies such as computerized tomography, diagnostic peritoneal lavage and abdominal ultrasound have improved both sensitivity and specificity of evaluation in blunt and penetrating trauma, thus decreasing the rate of negative coeliotomy. A retrospective study of 50 consecutive negative laparotomies (10.5 per cent of all trauma laparotomies) at our Trauma Center revealed a morbidity rate of 22 per cent and mortality of 6 per cent. Although the negative coeliotomy rate was lower for blunt than penetrating trauma, morbidity was significantly higher for blunt trauma. Extra-abdominal injury alone could not account for this difference. We conclude that negative coeliotomy in penetrating trauma does not carry excessive morbidity. Negative coeliotomy in blunt trauma is accompanied by high morbidity and mortality, so adjunct diagnostic procedures should be utilized in this population in an effort to minimize negative laparotomies.

Diagnosis of unsuspected facial fractures on routine head computerized tomographic scans in the unconscious multiply injured patient.

PURPOSE: This article assessed the value of routine head computerized axial tomographic (CT) scans for diagnosis of unsuspected facial fractures and its clinical implications in the multiply injured patient who is intubated, unconscious, or sedated at the time of initial assessment and requires a head CT scan to assess for brain injury. METHODS: At a level I trauma center from June 1, 1992 to June 1, 1993 all intubated blunt trauma patients who required routine CT scan evaluation at initial assessment were studied prospectively. Routine scanning started at the foramen magnum and included the maxilla. Patients who died within the first 24 hours were excluded. RESULTS: The study population included 116 patients (85 male, 21 female) aged 12 to 85 years (mean, 28 years) with injury severity scores ranging from 1 to 50 (mean, 23). The mechanism of injury was: motor vehicle accidents (n = 74), motorcycling (n = 5), pedestrians accidents (n = 13), falls (n = 10), bicycling (n = 5), assaults (n = 8), and boating accident (n = 1). There were 19 suspected facial fractures; 18 required surgical repair. There were 27 unsuspected facial fractures; 13 required surgical care. Three suspected fractures were ruled out. CONCLUSION: Routine head CT scans to assess for brain injury in the multiply injured patient are also very useful in the diagnosis of unsuspected facial fractures, almost half of which will require surgical intervention.

Elderly drivers involved in road crashes: a profile.

The ability of elderly citizens to drive safely has been the subject of ongoing debate. To identify the type of elderly driver who becomes involved in an injury-producing road crash, we profiled all drivers over 39 years of age admitted to our Level I Trauma Center over a 1-year period. Data were prospectively collected and drivers age 40-59 years were compared with those over 60 years. Eighty-four drivers age > or = 60 and 130 drivers age 40-59 were studied. Of the 84 elderly drivers, 67 were deemed at fault. Twenty-four of those crashes were due to driving errors, 12 due to syncopes, and in 20 no crash cause was determined. Fifty-three of the 67 at fault drivers had significant underlying medical problems, compared to 9 of 17 deemed not at fault. Only four were legally intoxicated. Of the 130 drivers in the comparison group, only 19 had significant underlying medical problems; in three syncope was suspected; 18 were legally intoxicated. We conclude from our data that underlying medical disorders occur frequently in elderly drivers and may contribute to their incidence of road crashes.