Single Body Site Research Articles

Omics approaches to discover pathophysiological pathways contributing to human pain.

Omics approaches to discover pathophysiological pathways contributing to human pain.

Temporal and Spatial Changes in the Microbiome Following Pediatric Severe Traumatic Brain Injury.

The microbiome may be affected by trauma and critical illness. Many studies of the microbiome in critical illness are restricted to a single body site or time point and confounded by preexisting conditions. We report temporal and spatial alterations in the microbiome of previously healthy children with severe traumatic brain injury (TBI). We collected oral, rectal, and skin swabs within 72 hours of admission and then twice weekly until ICU discharge. Samples were analyzed by 16S rRNA gene amplicon sequencing. Children undergoing elective outpatient surgery served as controls. Alpha and beta diversity comparisons were performed with Phyloseq, and differentially abundant taxa were predicted using Analysis of Composition of Microbiomes. Five quaternary-care PICUs. Patients less than 18 years with severe TBI requiring placement of an intracranial pressure monitor. None. Three hundred twenty-seven samples were analyzed from 23 children with severe TBI and 35 controls. The community composition of initial oral (F = 3.2756, R2 = 0.0535, p = 0.012) and rectal (F = 3.0702, R2 = 0.0649, p = 0.007) samples differed between TBI and control patients. Rectal samples were depleted of commensal bacteria from Ruminococcaceae, Bacteroidaceae, and Lachnospiraceae families and enriched in Staphylococcaceae after TBI (p < 0.05). In exploratory analyses, antibiotic exposure, presence of an endotracheal tube, and occurrence of an infection were associated with greater differences of the rectal and oral microbiomes between TBI patients and healthy controls, whereas enteral nutrition was associated with smaller differences (p < 0.05). The microbiome of children with severe TBI is characterized by early depletion of commensal bacteria, loss of site specificity, and an enrichment of potential pathogens. Additional studies are needed to determine the impact of these changes on clinical outcomes.

Methods for efficacy evaluations of antibacterial treatments in multiple body-site infection trials

ABSTRACTUnmet medical need exists for serious bacterial diseases caused by multidrug-resistant infections, necessitating an urgent need for newer therapies with greater treatment benefits to patients. For meeting this need, the usual approach has been to conduct separate clinical trials, each trial targeting infection at a single body-site, e.g., for respiratory tract, intra-abdominal site, urinary tract, or blood. However, for the unmet medical need situations, this approach seems inefficient for developing antibacterial drugs with activity against single species or against multiple species of bacteria for a broader indication. Instead, a streamlined clinical development program for such situations can benefit by considering multiple body-site infection trials. Such trials would enroll patients with infections at different body-sites, but with similar severity and comorbidity for avoiding potential treatment effect heterogeneity. Such trials, when properly designed and conducted, can be informative and can save time and resources in drug development. Goals for such trials would be to first demonstrate that there is evidence of an overall treatment effect, and then to show that the treatment effects at individual body-sites reveal consistency in contributing to the overall treatment effect, or to identify a subset of body-sites for which greater treatment effect can be supported by a specified statistical decision criterion. For this, we propose here an information-based procedure for the demonstration of treatment effect overall across all body-sites, or for a subset of body-sites, on considering two types of error rates of falsely concluding treatment effect.

Transmission Clusters of Methicillin-Resistant Staphylococcus Aureus in Long-Term Care Facilities Based on Whole-Genome Sequencing.

OBJECTIVE To define how often methicillin-resistant Staphylococcus aureus (MRSA) is spread from resident to resident in long-term care facilities using whole-genome sequencing DESIGN Prospective cohort study SETTING A long-term care facility PARTICIPANTS Elderly residents in a long-term care facility METHODS Cultures for MRSA were obtained weekly from multiple body sites from residents with known MRSA colonization over 12-week study periods. Simultaneously, cultures to detect MRSA acquisition were obtained weekly from 2 body sites in residents without known MRSA colonization. During the first 12-week cycle on a single unit, we sequenced 8 MRSA isolates per swab for 2 body sites from each of 6 residents. During the second 12-week cycle, we sequenced 30 MRSA isolates from 13 residents with known MRSA colonization and 3 residents who had acquired MRSA colonization. RESULTS MRSA isolates from the same swab showed little genetic variation between isolates with the exception of isolates from wounds. The genetic variation of isolates between body sites on an individual was greater than that within a single body site with the exception of 1 sample, which had 2 unrelated strains among the 8 isolates. In the second cycle, 10 of 16 residents colonized with MRSA (63%) shared 1 of 3 closely related strains. Of the 3 residents with newly acquired MRSA, 2 residents harbored isolates that were members of these clusters. CONCLUSIONS Point prevalence surveys with whole-genome sequencing of MRSA isolates may detect resident-to-resident transmission more accurately than routine surveillance cultures for MRSA in long-term care facilities. Infect Control Hosp Epidemiol 2016;37:685-691.

Moving pictures of the human microbiome

BackgroundUnderstanding the normal temporal variation in the human microbiome is critical to developing treatments for putative microbiome-related afflictions such as obesity, Crohn's disease, inflammatory bowel disease and malnutrition. Sequencing and computational technologies, however, have been a limiting factor in performing dense time series analysis of the human microbiome. Here, we present the largest human microbiota time series analysis to date, covering two individuals at four body sites over 396 timepoints.ResultsWe find that despite stable differences between body sites and individuals, there is pronounced variability in an individual's microbiota across months, weeks and even days. Additionally, only a small fraction of the total taxa found within a single body site appear to be present across all time points, suggesting that no core temporal microbiome exists at high abundance (although some microbes may be present but drop below the detection threshold). Many more taxa appear to be persistent but non-permanent community members.ConclusionsDNA sequencing and computational advances described here provide the ability to go beyond infrequent snapshots of our human-associated microbial ecology to high-resolution assessments of temporal variations over protracted periods, within and between body habitats and individuals. This capacity will allow us to define normal variation and pathologic states, and assess responses to therapeutic interventions.

Failure of particulate bioglass to prevent experimental staphylococcal infection of open tibial fractures

range from 355 to 500 mm, consisting of 45 wt% SiO2/24.5 wt% Na2O/24.5 wt% CaO/6 wt% P2O5) in vivo by examining its efficacy in reducing the rate of infection by Staphylococcus aureus after the fixation of open tibial fractures in rabbits. An in vivo test was carried out with male rabbits split into two groups infected with S. aureus ATCC 25923 at the right tibial fracture sites fixed with plates and screws, with 300 mg of particulate Bioglass w implanted in the fracture and surrounding area for the Bioglass w group, in accordance with the guidelines of the Local Animal Welfare Committee. Six weeks after the operation, the anteroposterior and lateral radiographs of the right tibia were taken and scored, the specimens from the plate and the bone were collected for microbiological evaluation, and the tibias were cut off for histopathological examination and scoring. There was no significant difference between the rates of infection in the control group (60%) and the Bioglass w group (66.7%) (P ¼ 0.35; Table 1). Similarly, there were no significant differences between the radiographic and histological scores of the control group (4.5 and 2.5, respectively) and the Bioglass w group (4 and 3, respectively) (P ¼ 0.96 and 0.32, respectively; Wilcoxon test). It has been suggested that bioglass exerts antibacterial activity by increasing pH, osmotic effects and calcium ion concentrations. 4,5 The failure of Bioglass w to prevent infection in this model may reflect the difference between in vitro and in vivo environments. For example, when bioglass particles are released into local body fluids in vivo, the local pH may not change due to the buffering capacity of the fluids. One possible limitation of the current study is that only a single strain of S. aureus was used, and a single body site was investigated. Although the initial results presented here showed no evidence for efficacy of bioglass in vivo, scope remains for studies with other strains or species of bacteria and other body sites.

Chronic musculoskeletal pain rarely presents in a single body site: results from a UK population study

To investigate the frequency and health impact of chronic multi-site musculoskeletal pain, in a representative UK sample. Population postal questionnaire survey, using 16 general practices in the southeast of England, nationally representative urban/rural, ethnic and socioeconomic mix. A random selection of 4049 registered patients, aged 18 or over, were sent a questionnaire. The main outcome measures were chronic pain location, identified using a pain drawing; distress, pain intensity and disability as measured by the GHQ12 and the Chronic Pain Grade. A total of 2445 patients (60%) responded to the survey (44% male, mean age 52 yrs); 45% had chronic musculoskeletal pain. Of those with chronic pain, three quarters had pain in multiple sites (two or more sites). Variables significantly predicting this were: age under 55, [odds ratio (OR) 0.5, 95% confidence interval (CI) 0.4, 0.6]; psychological distress (OR 1.8, CI at 95% 1.4, 2.2) and high pain intensity (OR 5.2, CI at 95% 4.1, 6.7). Only 33% of multi-site pain distributions conformed to the American College of Rheumatology definition of chronic widespread pain. Multi-site chronic pain is more common than single-site chronic pain and is commonly associated with other problems. Indiscriminate targeting of research and care for chronic musculoskeletal pain on single sites may often be inappropriate.

Optimal Surveillance Culture Sites for Detection of Methicillin-Resistant Staphylococcus aureus in Newborns

We describe two outbreaks among newborns, one caused by community-associated methicillin-resistant Staphylococcus aureus (MRSA) and the other by hospital-associated MRSA. The umbilicus, rectum, and nares were tested for colonization. We found that no single body site had optimal sensitivity when tested alone. The combination of umbilical and nasal swabs achieved a sensitivity of >90%.

Lethal cyanide inhalation with post-mortem trans-cutaneous cyanide diffusion

A 27-year-old worker in a metal processing factory was found dead in a basin, sitting in a solution containing potassium dicyano argentate, potassium cyanide, master batch and brightener ’Elfit 73’. The worker was wearing an acid-resisting overall, rubber boots and a simple dust respirator. While the cyanide concentration in the stomach contents was only 0.05 μg/ml, it was 7.7 μg/g in the lung tissue, 6.3 μg/ml in the heart blood and 31 μg/ml in the femoral vein blood. The different concentrations suggest an initial lethal inhalation of cyanide and an extensive post-mortem diffusion of cyanide through primarily non-injured skin of buttocks and legs. The possibility of a post-mortem cyanide diffusion bars from concluding a vital sign from a high cyanide concentration in a blood sample of one single body site.

The application of information technology to regional, national, and global surveillance of antimicrobial resistance.

Establishing local, national, and global surveillance networks for monitoring the dissemination of antimicrobial resistance and detecting the emergence of new resistance mechanisms has been recommended by the American Society for Microbiology Task Force on Antibiotic Resistance and other national organizations. While the need to develop and deploy surveillance strategies cannot be argued, the design and implementation of effective regional, national, and global surveillance networks is a daunting task with geographic, participatory, logistic, and funding challenges. Using information technology to capture, combine, collate, and analyze daily clinical microbiology laboratory data would seem to be a far more robust and logical approach to surveillance than traditional centralized studies that generally focus on only a few bacterial species or on isolates from a single body site. Information technology allows long-term, continuous tracking of antimicrobial resistance trends among large numbers of isolates over a broad range of species, and across entire regions or countries. The rationale for wanting to use networks of clinical laboratories for surveillance is obvious: susceptibility data are generated every day by thousands of laboratories located around the world, and most of these laboratories perform antimicrobial susceptibility testing on the bacterial species that pose the greatest public health problems. By virtue of information technology, large volumes of data can readily be managed and stored to allow timely and thorough analysis on institutional, regional, national, and global levels.

Where does it hurt? Describing the body locations of chronic pain

Chronic pain patients have complex problems. Due to this, much research effort has been expended on the classification of pain patients and the classification of pain problems. A mainstay of most pain classification systems is the use of the physical location of the pain. Yet describing the location of the patient's pain is not straightforward. Many patients have pain at multiple sites and thus simple statements such as ‘patients with low back pain’ have considerable ambiguity. Does the statement refer to patients with pain just in the lower back or those with low back pain who may also have pain elsewhere (e.g. pain down the leg)? If patients do have pain elsewhere, at what other body sites and what are the implications of this? This paper presents data on the body location of pain for a large sample of 5279 patients seen with chronic pain in Scotland and the north of England. It shows that one-third of patients have pain in multiple locations, and that using a single body site to classify patients leads to groups with large overlaps. Thus, 38% of patients reported pain in the ‘lower back/spine’ and 34% reported pain in the `buttock, leg, foot' — but there was considerable overlap between these groups. Nineteen percent of patients reported pain in both of these body areas, and one-third of these patients also had pain in at least one further body area. Furthermore, a systematic look at patients with diverse physical pain locations but a single site in common shows large demographic differences. Common pain groupings help to reduce the confusion; 13 pain site descriptions were able to account for 82% of all patients. The remaining 18% of patients had pain in a combination of body sites which they shared with fewer than 1% of other patients. Thus, pain patients are widely heterogeneous and complex. Patients report pain in more complex patterns than can easily be captured by a single body-site code. Further, large demographic differences between patients with different painful sites, even when they have at least one pain site in common, suggests that grouping patients based on a single site descriptor may be inappropriate. These findings have important implications for chronic pain description and classification.

Body site variation of cool perception thresholds, with observations on paradoxical heat.

Thresholds for the perception of coolness and heat pain were determined in sessions that randomly intermixed temperature increases and decreases. Four body sites were tested bilaterally: thenar eminence of the hand, plantar surface of the foot, dorsolateral forearm, and lateral calf. Coolness thresholds were lowest for the hand, intermediate for the forearm, and highest for the leg and foot. Laterality differences were not statistically significant. In 34% of the sessions, subjects did not consistently report cool or cold sensations with detectable temperature decreases. When they did not report cool or cold, they most often reported heat or pain, thus exhibiting the phenomenon of "paradoxical heat." There were significantly more paradoxical heat responses when cooling stimuli were intermixed with painfully hot stimuli than when they were intermixed with only warm stimuli. There was no significant correlation observed between thresholds for coolness and heat pain, either across body sites or across subjects at any single body site. This result implies that the various factors relevant to thermal sensitivity (i.e., thermal properties of the epidermis, innervation density) are differentially important for cool versus heat pain perception.

Estimation of the post mortem period by multiple-site temperature measurements and the use of a new algorithm

The estimation of the post mortem period, in cases where death occured under suspicious circumstances, is usually attempted using temperature measurements taken at a single body site. Early investigations of the validity of such an approach use the abdominal skin surface, the axilla and the rectum as measurement sites (B.H. Knight, Forensic Sci. Int., 36 (1987) 47–55). However, it has recently become more common to use the rectum alone, though the ear and the nasal passages have also been utilized. Whatever site is employed, the estimates are frequently found to be inaccurate. There are several fundamental reasons for these inaccuracies, the most prominent being the unknown variation in the ambient temperature between the time of death and the commencement of measurements, and the unknown body temperature at the time of death. This paper proposes a method of overcoming the above difficulties by taking a series of measurements concurrently at a number of body sites, a technique used by several previous workers (B.H. Knight, Forensic Sci. Int., 36 (1987) 47–55). Initial investigations have shown that an improved estimation of post mortem period is obtainable by the application of a suitable decision-making algorithm.

Serum chloramphenicol levels and the intramuscular bioavailability of several parenteral formulations of chloramphenicol in ruminants

Summary Serum chloramphenicol concentrations were determined by microbiological and chemical assay methods in cows, ewes, and goats treated parenterally with seven different veterinary parenteral chloramphenicol products, including the water soluble sodium succinate ester of chloramphenicol and solutions of 20%, 25% and 50% of chloramphenicol base in various organic solvents. Serum drug concentrations were analyzed for the effect of product formulation differences, dosage, whether the drug was administered i.m. at a single body site or to two sites, and the method of assay, on the absorption from the injection site, peak drug levels, and the persistence in serum of effective concentrations of the drug i.e. 5 to 10 ug / ml. Although differences were observed among the 6 products containing chloramphenicol base in respect to absorption rate and peak serum drug levels, and although these differences significantly influenced the persistence of microbiologically-active serum drug concentrations at the level of ≥ 10 μg / ml, they did not at the level of ≥ 5 μg / ml. In the animal species examined, injections given at 2 sites appeared to influence the duration of predetermined serum drug levels more than the differences among the products in respect of the absorption and elimination rates from serum, the peak serum concentrations, and the dose. The shapes of the concentration-to-time curves in cows and ewes injected with the same dose of a given product were essentially the same, but they were different in goats. Serum chloramphenicol concentrations measured chemically after treatment with chloramphenicol base were 20% to 46% higher than those measured microbiologically. For 60 minutes after the sodium succinate ester had been administered i.v. and i.m. to ewes, the chemically determined chloramphenicol levels were more than twice as high as the respective concentrations determined by microbiological assay, but thereafter, the magnitude of those differences was not greater than observed after treatment with chloramphenicol base. Intramuscular bioavailability of the products containing chloramphenicol base injected at 2 sites was rather poor (51% to 80.5%ofthe dose) and even lower values were calculated after injection at a single site. Results are briefly discussed of the effect of dosage form on the persistence of microbiologically effective serum drug levels. A dose of at least 50 mg / kg to be administered i.m. at two sites are essential prerequisits for chloramphenicol therapy in ruminants.