A quantitative approach for measuring the reservoir of latent HIV-1 proviruses.

A stable latent reservoir for HIV-1 in resting CD4+ T cells is the principal barrier to a cure1-3. Curative strategies that target the reservoir are being tested4,5 and require accurate, scalable reservoir assays. The reservoir was defined with quantitative viral outgrowth assays for cells that release infectious virus after one round of T cell activation1. However, these quantitative outgrowth assays and newer assays for cells that produce viral RNA after activation6 may underestimate the reservoir size because one round of activation does not induce all proviruses7. Many studies rely on simple assays based on polymerase chain reaction to detect proviral DNA regardless of transcriptional status, but the clinical relevance of these assays is unclear, as the vast majority of proviruses are defective7-9. Here we describe a more accurate method of measuring the HIV-1 reservoir that separately quantifies intact and defective proviruses. We show that the dynamics of cells that carry intact and defective proviruses are different in vitro and in vivo. These findings have implications for targeting the intact proviruses that are a barrier to curing HIV infection

Pre-operative fluid resuscitation in the emergency general surgery septic patient: does it really matter?

Abstract Objective Emergency general surgery (EGS) patients presenting with sepsis remain a challenge. The Surviving Sepsis Campaign recommends a 30 mL/kg fluid bolus in these patients, but recent studies suggest an association between large volume crystalloid resuscitation and increased mortality. The optimal amount of pre-operative fluid resuscitation prior to source control in patients with intra-abdominal sepsis is unknown. This study aims to determine if increasing volume of resuscitation prior to surgical source control is associated with worsening outcomes. Methods We conducted an 8-year retrospective chart review of EGS patients undergoing surgery for abdominal sepsis within 24 h of admission. Patients in hemorrhagic shock and those with outside hospital index surgeries were excluded. We grouped patients by increasing pre-operative resuscitation volume in 10 ml/kg intervals up to > 70 ml/kg and later grouped them into  30 ml/kg (p = 0.02). These groups had median qSOFA scores (1.0 vs. 1.0, p = 0.06). There were no differences in time to operation (6.1 vs 4.9 h p = 0.11), ventilator days (1 vs 3, p = 0.08), or hospital LOS (8 vs 9 days, p = 0.57). Relative risk regression correcting for age and physiologic factors showed no significant differences in mortality between the fluid groups. Conclusions Greater pre-operative resuscitation volumes were initially associated with significantly higher mortality, despite similar organ failure scores. However, fluid volumes were not associated with mortality following adjustment for other physiologic factors in a regression model. The amount of pre-operative volume resuscitation was not associated with differences in time to operation, ventilator days, ICU or hospital LOS

On equal footing: Trends in ankle/foot injuries for men vs. women

<p><b>Objectives</b>: The objective of the current study was to examine trends in ankle/foot (A/F) injuries during the period 2001–2014, in order to determine whether the incidence of these injuries has changed and whether a previously identified difference in risk by gender still existed. In addition, other driver and crash-related risk factors were examined separately for men and women.</p> <p><b>Methods</b>: Passenger vehicle drivers aged 16+ were identified from NASS-CDS; weighted data were analyzed for model years 2001–2014. Model years (MY) were grouped as 2001–2004 (older) vs. 2005–2014 (newer), and drivers in frontal crashes were included. Ankle injuries included fractures and dislocations to the malleolus and distal tibia/fibula. Foot injuries included fractures and dislocations of the talus, calcaneus, and tarsal/metatarsal bones. Logistic regression models were constructed to identify risk factors, including MY, age, belt use, toepan/instrument panel intrusion, and body mass index (BMI) separately for each gender using odds ratios.</p> <p><b>Results</b>: The incidence of A/F injuries declined significantly between older and newer MY, especially for women. Whereas before MY 2005, ankle and foot injury risk was significantly higher for women than men, risks for ankle injury are now virtually the same for both genders, and women are only 1.2 times more likely than men to sustain a foot injury in a frontal crash. From multivariable regression models, however, it is apparent that there are different risk factors for A/F injuries for men vs. women. Body weight was a significant factor for both groups, but for men it was a risk only for those extremely obese, whereas for women those who were categorized as overweight were also at increased risk. Age greater than 55 was also found to be a risk factor for foot injuries among women but not men. For men and women, toepan intrusion remained the most important factor for both foot and ankle injuries, with significantly higher odds ratios noted for men. Foot pedals were a more likely injury source for women, whereas the toepan was more likely for men. In addition, belt use was protective for ankle injuries in women but not men.</p> <p><b>Conclusions</b>: Significant declines in A/F injuries have been noted in recent years, especially for women, whose risks are now similar to those for men. However, significant risk factors remain for each gender, primarily related to body habitus (BMI) and toepan intrusion. Age was a risk factor for foot injuries among women, for whom the foot pedals were more likely to be an injury source. Toepan intrusion remains a major factor for both men and women, but, with the exception of 30+ cm of intrusion, odds ratios were primarily much higher for men in each category of intrusion.</p