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Differentiating between self-resolving viral infections and bacterial infections in children who are febrile is a common challenge, causing difficulties in identifying which individuals require antibiotics. Studying the host response to infection can provide useful insights and can lead to the identification of biomarkers of infection with diagnostic potential. This study aimed to identify host protein biomarkers for future development into an accurate, rapid point-of-care test that can distinguish between bacterial and viral infections, by recruiting children presenting to health-care settings with fever or a history of fever in the previous 72 h.

AbstractObjectives:Healthcare workers (HCWs) are a high-priority group for coronavirus disease 2019 (COVID-19) vaccination and serve as sources for public information. In this analysis, we assessed vaccine intentions, factors associated with intentions, and change in uptake over time in HCWs.Methods:A prospective cohort study of COVID-19 seroprevalence was conducted with HCWs in a large healthcare system in the Chicago area. Participants completed surveys from November 25, 2020, to January 9, 2021, and from April 24 to July 12, 2021, on COVID-19 exposures, diagnosis and symptoms, demographics, and vaccination status.Results:Of 4,180 HCWs who responded to a survey, 77.1% indicated that they intended to get the vaccine. In this group, 23.2% had already received at least 1 dose of the vaccine, 17.4% were unsure, and 5.5% reported that they would not get the vaccine. Factors associated with intention or vaccination were being exposed to clinical procedures (vs no procedures: adjusted odds ratio [AOR], 1.39; 95% confidence interval [CI], 1.16–1.65) and having a negative serology test for COVID-19 (vs no test: AOR, 1.46; 95% CI, 1.24–1.73). Nurses (vs physicians: AOR, 0.24; 95% CI, 0.17–0.33), non-Hispanic Black (vs Asians: AOR, 0.35; 95% CI, 0.21–0.59), and women (vs men: AOR, 0.38; 95% CI, 0.30–0.50) had lower odds of intention to get vaccinated. By 6-months follow-up, >90% of those who had previously been unsure were vaccinated, whereas 59.7% of those who previously reported no intention of getting vaccinated, were vaccinated.Conclusions:COVID-19 vaccination in HCWs was high, but variability in vaccination intention exists. Targeted messaging coupled with vaccine mandates can support uptake.

AbstractObjective:To determine the changes in severe acute respiratory coronavirus virus 2 (SARS-CoV-2) serologic status and SARS-CoV-2 infection rates in healthcare workers (HCWs) over 6-months of follow-up.Design:Prospective cohort study.Setting and participants:HCWs in the Chicago area.Methods:Cohort participants were recruited in May and June 2020 for baseline serology testing (Abbott anti-nucleocapsid IgG) and were then invited for follow-up serology testing 6 months later. Participants completed monthly online surveys that assessed demographics, medical history, coronavirus disease 2019 (COVID-19), and exposures to SARS-CoV-2. The electronic medical record was used to identify SARS-CoV-2 polymerase chain reaction (PCR) positivity during follow-up. Serologic conversion and SARS-CoV-2 infection or possible reinfection rates (cases per 10,000 person days) by antibody status at baseline and follow-up were assessed.Results:In total, 6,510 HCWs were followed for a total of 1,285,395 person days (median follow-up, 216 days). For participants who had baseline and follow-up serology checked, 285 (6.1%) of the 4,681 seronegative participants at baseline seroconverted to positive at follow-up; 138 (48%) of the 263 who were seropositive at baseline were seronegative at follow-up. When analyzed by baseline serostatus alone, 519 (8.4%) of 6,194 baseline seronegative participants had a positive PCR after baseline serology testing (4.25 per 10,000 person days). Of 316 participants who were seropositive at baseline, 8 (2.5%) met criteria for possible SARS-CoV-2 reinfection (ie, PCR positive >90 days after baseline serology) during follow-up, a rate of 1.27 per 10,000 days at risk. The adjusted rate ratio for possible reinfection in baseline seropositive compared to infection in baseline seronegative participants was 0.26 (95% confidence interval, 0.13–0.53).Conclusions:Seropositivity in HCWs is associated with moderate protection from future SARS-CoV-2 infection.

Type 1 diabetes is associated with lower bone mineral density (BMD) and increased fracture risk, but little is known regarding the effects of diabetes-related factors on BMD. We assessed whether these factors are associated with lower hip BMD among older adults with type 1 diabetes.

Diabetes is one of the world's fastest growing health challenges. Insulin therapy remains a useful regimen for many elderly patients, such as those with moderate to severe hyperglycemia, type 1 diabetes, hyperglycemic emergencies, and those who fail to maintain glucose control on non-insulin agents alone. Recent clinical trials have shown that several non-insulin agents as monotherapy, or in combination with low doses of basal insulin, have comparable efficacy and potential safety advantages to complex insulin therapy regimens. Determining the most appropriate diabetes management plan for older hospitalized patients requires consideration of many factors to prevent poor outcomes related to dysglycemia.

Previous studies have shown a relationship between glycemic control and posttransplant morbidity.

There is limited research using real‐world data to evaluate protective cardiovascular effects of glucagon‐like peptide‐1 (GLP‐1) agonists among adults with type 2 diabetes (T2D) early in treatment. We conducted a retrospective, active comparator cohort study using 2011–2015 administrative claims data to compare cardiovascular disease (CVD) event rates following initiation of exenatide extended‐release (E‐ER), exenatide immediate‐release (E‐IR) or liraglutide in T2D adults who previously received no other antidiabetic medication (ADM) except metformin. The primary outcome was time to first major adverse CVD event (ischaemic heart disease, stroke, congestive heart failure or peripheral arterial disease) after starting GLP‐1. Cox proportional hazards regression was used to model the association between index GLP‐1 and CVD events, adjusting for baseline patient, prescriber and plan characteristics. Primary analyses included all patients with ≥2 prescription fills for the index GLP‐1, regardless of subsequent refill adherence or initiation of other ADM after index date. Compared with liraglutide, neither E‐ER nor E‐IR was associated with risk of composite major CVD events (hazard ratios [HRs] for E‐ER and E‐IR: 1.33 [95% C.I. 0.73–2.39] and 1.30 [0.81–2.09]). No associations were observed between event rates for individual CVD components. The HR for an ischaemic event with E‐IR relative to liraglutide was 1.85 (95% C.I. 0.97–3.53). Adjusting for time‐varying exposure to other ADM and CVD medications after index date produced similar results. Initiating either immediate or extended‐release exenatide rather than liraglutide was not associated with significant differences in CVD risk in this observational real‐world study. We conducted a retrospective, active comparator cohort study using 2011‐2015 administrative claims data to compare cardiovascular disease (CVD) event rates following initiation of exenatide extended‐release (E‐ER), exenatide immediate‐release (E‐IR), or liraglutide in T2D adults who previously received no other antidiabetic medication (ADM) except metformin. The primary outcome was time to first major adverse CVD event (ischemic heart disease, stroke, congestive heart failure, or peripheral arterial disease) after starting GLP‐1. Compared with liraglutide, neither E‐ER nor E‐IR was associated with risk of composite major CVD events [hazard ratios (HRs) for E‐ER and E‐IR: 1.33 [95% C.I. 0.73‐2.39] and 1.30 [0.81‐2.09]]. No associations were observed between event rates for individual CVD components. The HR for an ischemic event with E‐IR relative to liraglutide was 1.85 (95% C.I. 0.97‐3.53) and adjusting for time‐varying exposure to other ADM and CVD medications after index date produced similar results. Initiating either immediate or extended release exenatide rather than liraglutide was not associated with significant differences in CVD risk in this observational real‐world study.

Background/Objectives:: The association of weight changes with cardiometabolic biomarkers in South Asians has been sparsely studied. Subjects/Methods:: We measured cardiometabolic biomarkers at baseline and after 3 years in the Prevention of Diabetes and Obesity in South Asians Trial. We investigated the effect of a lifestyle intervention on biomarkers in the randomized groups. In addition, treating the population as a single cohort, we estimated the association between change in weight and change in biomarkers. Results:: Complete data were available at baseline and after 3 years in 151 participants. At 3 years, there was an adjusted mean reduction of 1·44?kg (95% confidence interval (95% CI): 0.18–2.71) in weight and 1.59?cm (95% CI: 0.08–3.09) in waist circumference in the intervention arm as compared with the control arm. There was no clear evidence of difference between the intervention and control arms in change of mean value of any biomarker. As a single cohort, every 1?kg weight reduction during follow-up was associated with a reduction in triglycerides (-1.3%, P=0.048), alanine aminotransferase (-2.5%, P=0.032), gamma-glutamyl transferase (-2.2%, P=0.040), leptin (-6.5%, P<0.0001), insulin (-3.7%, P=0.0005), fasting glucose (-0.8%, P=0.0071), 2-h glucose (-2.3%, P=0.0002) and Homeostatic Model Assessment of insulin resistance (HOMA-IR: -4.5%, P=0.0002). There was no evidence of associations with other lipid measures, tissue plasminogen activator, markers of inflammation or blood pressure. Conclusions:: We demonstrate that modest weight decrease in SAs is associated with improvements in markers of total and ectopic fat as well as insulin resistance and glycaemia in South Asians at risk of diabetes. Future trials with more intensive weight change are needed to extend these findings.

Patients who undergo solid organ transplantation may have preexisting diabetes mellitus (DM), develop new-onset DM after transplantation (NODAT), or have postoperative hyperglycemia that resolves shortly after surgery. Although insulin is usually used to control hyperglycemia in the hospital, following discharge most of the usual diabetes oral and parenteral medications can be used in treatment. However, when there are comorbidities such as impaired kidney or hepatic function, or heart disease, special precautions may be necessary. In addition, drug-drug interactions, such as drugs interacting with CYP3A4 enzyme pathway, require additional consideration because of possible interaction with immunosuppressive drug metabolism.

Introduction:Branched chain amino acids (BCAA), measured at a single timepoint in midlife, are directly associated with risk for incident type 2 diabetes mellitus (DM), a strong determinant of cardiovascular disease risk. However, the trajectories (traj) of BCAAs through young adulthood and their associations with DM in midlife are unknown.Methods:We used NMR spectroscopy to measure serum BCAA levels from up to 3,081 Coronary Artery Risk Development in Young Adults (CARDIA) participants who attended the Year(Y) 2, 7, 15, 20, and 30 exams. We used latent class modeling to generate BCAA traj groups. To quantify associations between BCAA traj and prevalent DM* at the Y30 exam, we excluded participants with DM at Y2, and modeled traj groups from Y2 to Y30. To quantify associations between BCAA traj and incident DM by the Y30 exam, we excluded participants who developed DM by the Y20 exam and modeled traj from Y2 to Y20. We used adjusted** logistic regression to quantify the associations between traj group and prevalent and incident DM (at Y30), separately.Results:Among 3,081 participants (mean age at Y2: 27y), there were 3 BCAA traj groups: 1,427 participants in the low-stable group, 1,384 in the moderate-stable group, and 270 in the high-increasing group. Male sex, Black race, and higher body mass index were more common in the higher BCAA traj groups. Compared with the low-stable BCAA traj group (reference), the moderate-stable and high-increasing BCAA traj groups were associated with prevalent DM at Y30 (OR [95thCI]: moderate-stable, 2.59 [1.90-3.55]; high-increasing, 6.03 [3.86-9.43]). Moderate-stable and high-increasing traj groups were associated with incident DM at Y30 (OR [95thCI]: moderate-stable, 1.56 [1.02-2.39]; high-increasing, 2.20 [1.25-3.87]; low-stable, reference).Conclusions:BCAA levels track, on average, over a 28-year span in most young adults, but serial measurements identify subpopulations with rising levels and high risk of DM in later life.

Solid-pseudopapillary neoplasms (SPNs) are rare pancreatic tumors, which occur most frequently in young women and are associated with an excellent prognosis. Computed tomography (CT) is used most commonly to identify these lesions, but there are few studies evaluating the role of endoscopic ultrasound (EUS) and fine needle aspiration (EUS-FNA) in the assessment of SPN. The aim of the study was to determine the incremental diagnostic yield of EUS-FNA compared with CT or EUS in the evaluation of patients with SPN. A retrospective chart review of consecutive patients diagnosed with SPN who underwent CT, EUS, and EUS-FNA at five centers from three countries from 1998 to 2013. Patient demographics, imaging, endoscopic studies, cytopathology, and histology were reviewed. Thirty-four patients were identified with SPN. There were 31 (91.2 %) females, with a mean age at diagnosis of 37 years (range 16-81). The most common presenting symptom was abdominal pain which was present in 59 %. SPNs were incidentally detected in 14 (41.2 %) of the patients. The median tumor size was 4.2 cm (range 1.9–9.4). No patient had evidence of local or distant metastases. The most common appearance on EUS was of a mixed solid-cystic lesion (67.6 %). The diagnostic yield of CT and EUS alone was 23.5 and 41.2 %, respectively. CT and EUS combined had a diagnostic yield of 52.9 %. The addition of EUS-FNA significantly increased the diagnostic yield to 82.4 % compared with either CT or CT and EUS (p< 0.005). There were no reported adverse events reported. SPNs are rare pancreatic tumors primarily affecting young women. The addition of EUS-FNA significantly increased the pre-operative diagnostic yield of SPN to 82.4 %.

The susceptibility to type 2 diabetes of people of south Asian descent is established, but there is little trial-based evidence for interventions to tackle this problem. We assessed a weight control and physical activity intervention in south Asian individuals in the UK.

Intensive glycemic control has been shown to positively impact outcomes in an intensive care setting. Whether this practice is beneficial after liver transplantation (LT) is not known.

Bumetanide 1 to 2 mg or metolazone 2.5 mg were administered by mouth separately and then in combination to eight normal men and women in order to determine whether a sequential blockade of sodium reabsorption with diuretic agents that act at different sites within the nephron leads to a supra‐additive diuretic effect. All three treatment regimens resulted in a significant weight loss and increased urine volume and the excretion of sodium, potassium, and chloride. A prolonged diuretic effect lasting up to 48 hours after administration occurred with metolazone alone. Although absolute and fractional chloride and potassium excretion and urine volume were higher after combined therapy (P < .05 or better) than after either drug alone, absolute sodium excretion after combination therapy was higher than excretion after bumetanide [P < .05) but not after metolazone. The percent of fractional sodium excretion after both drugs was greater than after either drug alone (P < .05). However, excretion of chloride, sodium, potassium, and fluid on the combined therapy day was less than the sum of excretion on each single drug therapy day. Thus, the combination of bumetanide and metolazone did not have a supra‐additive effect in normal subjects.

Apoptosis is a physiologic form of cell death present in many disease conditions. When the balance of mitosis versus apoptosis is altered, tumor‐like growth or degeneration of tissues may ensue. This appears to occur in several diseases, including those of the cardiovascular system, where apoptosis plays a key role in atherosclerosis and restenosis following angioplasty. Since c‐mycis upregulated in the pathogenesis of these diseases, we chose to study the sequential morphologic features of programmed cell death in vascular smooth muscle cells induced by c‐mycand by the adenovirus early gene E1 A. Morphology and timed events in apoptotic cell cultures were analyzed by scanning electron microscopy, transmission electron microscopy, and time‐lapse videomicroscopy. We observed that both c‐myc‐and E1A‐induced apoptosis (in serum‐free medium) resulted in numerous, tightly packed clusters of apoptotic blebs, as well as in one or two asymmetrically larger blebs. Transmission electron microscopy analysis revealed the larger blebs contained mostly nuclear chromatin, whereas the many smaller fragments often had little or no chromatin. Time‐lapse studies showed that apoptosis was induced at a slower rate in cells stably transfected with c‐mycversus those stably transfected with E1A. The early changes of apoptosis, including cell shrinkage and intense blebbing, occurred in under 5 min in both cells. Slight alterations such as cell size and further rounding occurred up to 8 h following the initial changes of apoptosis. Rather than being a part of the apoptotic response, release from the culture floor almost entirely resulted from movement of the culture flask. These studies provide aframework of timed morphologic events for future mechanistic investigation into the key aspects of mycand E1A‐induced apoptosis in vascular smooth muscle.