James Proudfoot

Coinfection with hepatitis B and D: Epidemiology, prevalence and disease in patients in Northern California

With no report on the overall prevalence and ramifications of hepatitis Delta virus (HDV) infection in the United States for more than two decades, the characteristics of chronic hepatitis B virus (CHB) patients coinfected with HDV, including clinical presentation, rate of hepatitis C virus tri‐infection, and HDV viral load, were assessed.

Diffusion Tensor Imaging Provides Evidence of Possible Axonal Overconnectivity in Frontal Lobes in Autism Spectrum Disorder Toddlers.

BACKGROUND Theories of brain abnormality in autism spectrum disorder (ASD) have focused on underconnectivity as an explanation for social, language, and behavioral deficits but are based mainly on studies of older autistic children and adults. METHODS In 94 ASD and typical toddlers ages 1 to 4 years, we examined the microstructure (indexed by fractional anisotropy) and volume of axon pathways using in vivo diffusion tensor imaging of fronto-frontal, fronto-temporal, fronto-striatal, and fronto-amygdala axon pathways, as well as posterior contrast tracts. Differences between ASD and typical toddlers in the nature of the relationship of age to these measures were tested. RESULTS Frontal tracts in ASD toddlers displayed abnormal age-related changes with greater fractional anisotropy and volume than normal at younger ages but an overall slower than typical apparent rate of continued development across the span of years. Posterior cortical contrast tracts had few significant abnormalities. CONCLUSIONS Frontal fiber tracts displayed deviant early development and age-related changes that could underlie impaired brain functioning and impact social and communication behaviors in ASD.

Afferent Inputs to Neurotransmitter-Defined Cell Types in the Ventral Tegmental Area

The ventral tegmental area (VTA) plays a central role in the neural circuit control of behavioral reinforcement. Though considered a dopaminergic nucleus, the VTA contains substantial heterogeneity in neurotransmitter type, containing also GABA and glutamate neurons. Here, we used a combinatorial viral approach to transsynaptically label afferents to defined VTA dopamine, GABA, or glutamate neurons. Surprisingly, we find that these populations received qualitatively similar inputs, with dominant and comparable projections from the lateral hypothalamus, raphe, and ventral pallidum. However, notable differences were observed, with striatal regions and globus pallidus providing a greater share of input to VTA dopamine neurons, cortical input preferentially on to glutamate neurons, and GABA neurons receiving proportionally more input from the lateral habenula and laterodorsal tegmental nucleus. By comparing inputs to each of the transmitter-defined VTA cell types, this study sheds important light on the systems-level organization of diverse inputs to VTA.

Noninvasive Transcutaneous Vagus Nerve Stimulation Decreases Whole Blood Culture‐Derived Cytokines and Chemokines: A Randomized, Blinded, Healthy Control Pilot Trial

The purpose of this study was to test the transcutaneous noninvasive vagus nerve stimulator (nVNS) (gammaCore©) device to determine if it modulates the peripheral immune system, as has been previously published for implanted vagus nerve stimulators.

Treatment of postmastectomy pain with ambulatory continuous paravertebral nerve blocks: a randomized, triple-masked, placebo-controlled study.

Background We aimed to determine with this randomized, triple-masked, placebo-controlled study if benefits are afforded by adding a multiple-day, ambulatory, continuous ropivacaine paravertebral nerve block to a single-injection ropivacaine paravertebral block after mastectomy. Methods Preoperatively, 60 subjects undergoing unilateral (n = 24) or bilateral (n = 36) mastectomy received either unilateral or bilateral paravertebral perineural catheter(s), respectively, inserted between the third and fourth thoracic transverse process(es). All subjects received an initial bolus of ropivacaine 0.5% (15 mL) via the catheter(s). Subjects were randomized to receive either perineural ropivacaine 0.4% or normal saline using portable infusion pump(s) [5 mL/h basal; 300 mL reservoir(s)]. Subjects remained hospitalized for at least 1 night and were subsequently discharged home where the catheter(s) were removed on postoperative day (POD) 3. Subjects were contacted by telephone on PODs 1, 4, 8, and 28. The primary end point was average pain (scale, 0–10) queried on POD 1. Results Average pain queried on POD 1 for subjects receiving perineural ropivacaine (n = 30) was a median (interquartile) of 2 (0–3), compared with 4 (1–5) for subjects receiving saline (n = 30; 95% confidence interval difference in medians, −4.0 to −0.3; P = 0.021]. During this same period, subjects receiving ropivacaine experienced a lower severity of breakthrough pain (5 [3–6] vs 7 [5–8]; P = 0.046) as well. As a result, subjects receiving perineural ropivacaine experienced less pain-induced physical and emotional dysfunction, as measured with the Brief Pain Inventory (lower score = less dysfunction): 14 (4–37) versus 57 (8–67) for subjects receiving perineural saline (P = 0.012). For the subscale that measures the degree of interference of pain on 7 domains, such as general activity and relationships, subjects receiving perineural saline reported a median score 10 times higher (more dysfunction) than those receiving ropivacaine (3 [0–24] vs 33 [0–44]; P = 0.035). In contrast, after infusion discontinuation, there were no statistically significant differences detected between treatment groups. Conclusions After mastectomy, adding a multiple-day, ambulatory, continuous ropivacaine infusion to a single-injection ropivacaine paravertebral nerve block results in improved analgesia and less functional deficit during the infusion. However, no benefits were identified after infusion discontinuation.

Intubation Attempts Increase the Risk for Severe Intraventricular Hemorrhage in Preterm Infants—A Retrospective Cohort Study

OBJECTIVE To evaluate whether neonates exposed to multiple intubation attempts within the first 4 days after birth have an increased incidence of intraventricular hemorrhage (IVH). STUDY DESIGN This is a retrospective cohort study of infants intubated during the first 4 days after birth. Infants had birth weights (BWs) less than 1500 g and were admitted to the neonatal intensive care unit (NICU) at the University of California, San Diego, between January 1, 2005, and July 30, 2009. A subgroup analysis was done for infants with BW less than 750 g. RESULTS A total of 308 infants with BW <1500 g, including 102 with a BW <750 g, were intubated within the first 4 days of life. The number of intubation attempts was significantly greater in infants with a BW <750 g who had severe IVH compared with those with mild or no IVH (OR 1.395, 95% CI 1.090-1.786, P = .008). For infants with BW <1500 g, the number of intubation attempts in the delivery room was significantly greater for infants with severe IVH (OR 1.317, 95% CI 1.052-1.649, P = .016). CONCLUSION Increased intubation attempts were associated with increased incidence of severe IVH in infants with BW less than 750 g and in infants less than 1500 g who were intubated only in the delivery room. Prospective studies are needed to further evaluate the relationship between intubation attempts and severe IVH.

Continuous Transversus Abdominis Plane (TAP) Blocks for Postoperative Pain Control after Hernia Surgery: A Randomized, Triple-Masked, Placebo-Controlled Study

BACKGROUND Single-injection transversus abdominis plane (TAP) block provides postoperative analgesia and decreases supplemental analgesic requirements. However, there is currently no evidence from randomized, controlled studies investigating the possible benefits of continuous TAP blocks. Therefore, the aim of this randomized, triple-masked, placebo-controlled study was to determine if benefits are afforded by adding a multiple-day, ambulatory, continuous ropivacaine TAP block to a single-injection block following hernia surgery. METHODS Preoperatively, subjects undergoing unilateral inguinal (N=19) or peri-umbilical (N=1) hernia surgery received unilateral or bilateral TAP perineural catheter(s), respectively. All received a ropivacaine 0.5% (20 mL) bolus via the catheter(s). Subjects were randomized to either postoperative perineural ropivacaine 0.2% or normal saline using portable infusion pump(s). Subjects were discharged home where the catheter(s) were removed the evening of postoperative day (POD) 2. Subjects were contacted on POD 0-3. The primary endpoint was average pain with movement (scale: 0-10) queried on POD 1. RESULTS Twenty subjects of a target 30 were enrolled due to the primary surgeons unanticipated departure from the institution. Average pain queried on POD 1 for subjects receiving ropivacaine (N=10) was a mean (standard deviation) of 3.0 (2.6) vs 2.8 (2.7) for subjects receiving saline (N=10; 95% confidence interval difference in means -2.9 to 3.4; P=0.86). There were no statistically significant differences detected between treatment groups in any secondary endpoint. CONCLUSIONS The results of this study do not support adding an ambulatory, continuous ropivacaine infusion to a single-injection ropivacaine TAP block for hernia surgery. However, the present investigation was underpowered, and further study is warranted.

Posttraumatic stress disorder influences the nociceptive and intrathecal cytokine response to a painful stimulus in combat veterans

OBJECTIVE Although posttraumatic stress disorder (PTSD) and chronic pain frequently occur in tandem, the pathophysiological mechanisms mediating this comorbidity are poorly understood. Because excessive inflammation occurs in both conditions, we examined the cerebrospinal fluid (CSF) concentrations of inflammatory response mediators interleukin 1-beta (IL-1β), interleukin 6 (IL-6), interleukin 8 (IL-8), tumor necrosis factor-alpha (TNFα) and interleukin 10 (IL-10) after prolonged suprathreshold pain stimulus in 21 male combat veterans; 10 with PTSD and 11 combat controls (CC). METHODS After completing baseline quantitative sensory testing (QST) and psychological profiling, all patients received an injection of capsaicin into the quadriceps muscle. Spontaneously reported pain was measured for 30min after the capsaicin injection. The evoked pain measure of temporal summation was tested between 70 and 110min post capsaicin injection. Inflammatory (IL-1β, IL-6, IL-8 TNFα) and anti-inflammatory (IL-10) CSF cytokines were measured before (baseline) and after capsaicin injection over a time frame of 110min. RESULTS Following intramuscular capsaicin injection, pro-inflammatory cytokines [TNFα, IL-6, IL-8] significantly increased (percent rise from baseline) in both groups, whereas IL-1β significantly increased in the PTSD group only. The anti-inflammatory cytokine IL-10 showed an immediate (within 10min) increase in the CC group; however, the IL-10 increase in the PTSD group was delayed and not consistently elevated until 70min post injection. CONCLUSION These findings show significant central nervous system (CNS) differences in the inflammatory response to a deep pain stimulus in combat veterans with and without PTSD. They support the concept that abnormally elevated neuroinflammatory response to pain stimuli may be one CNS mechanism accounting for the high co-occurrence of PTSD and pain.

Validated gene expression biomarker analysis for biopsy-based clinical trials in ulcerative colitis.

Accurate and reproducible measurement of expression of pro‐inflammatory cytokines in colonic biopsies from patients with ulcerative colitis (UC) is essential for proof‐of‐concept and mechanism‐of‐action studies. Few studies have rigorously established the number of biopsies required for accurate and reproducible biomarker measurements.

Neurological Outcomes After Presumed Childhood Encephalitis

OBJECTIVE To evaluate factors during acute presumed childhood encephalitis that are associated with development of long-term neurological sequelae. METHODS A total of 217 patients from Rady Childrens Hospital San Diego with suspected encephalitis who met criteria for the California Encephalitis Project were identified. A cohort of 99 patients (40 females, 59 males, age 2 months-17 years) without preexisting neurological conditions, including prior seizures or abnormal brain magnetic resonance imaging scans was studied. Mean duration of follow-up was 29 months. Factors that had a relationship with the development of neurological sequelae (defined as developmental delay, learning difficulties, behavioral problems, or focal neurological findings) after acute encephalitis were identified. RESULTS Neurological sequelae at follow-up was associated with younger age (6.56 versus 9.22 years) at presentation (P = 0.04) as well as an initial presenting sign of seizure (P = 0.03). Duration of hospital stay (median of 7 versus 15.5 days; P = 0.02) was associated with neurological sequelae. Of the patients with neurological sequelae, a longer hospital stay was associated with patients of an older age (P = 0.04). Abnormalities on neuroimaging (P = 1.00) or spinal fluid analysis (P = 1.00) were not uniquely associated with neurological sequelae. Children who were readmitted after their acute illness (P = 0.04) were more likely to develop neurological sequelae. There was a strong relationship between the patients who later developed epilepsy and those who developed neurological sequelae (P = 0.02). SIGNIFICANCE Limited data are available on the long-term neurological outcomes of childhood encephalitis. Almost half of our patients were found to have neurological sequelae at follow-up, indicating the importance of earlier therapies to improve neurological outcome.