The Envirome Web Service: Patient context at the point of care.

Patient context - the "envirome" - can have a significant impact on patient health. While envirome indicators are available through large scale public data sources, they are not provided in a format that can be easily accessed and interpreted at the point of care by healthcare providers with limited time during a patient encounter. We developed a clinical decision support tool to bring envirome indicators to the point of care in a large pediatric hospital system in the Kansas City region. The Envirome Web Service (EWS) securely geocodes patient addresses in real time to link their records with publicly available context data. End-users guided the design of the EWS, which presents summaries of patient context data in the electronic health record (EHR) without disrupting the provider workflow. Through surveys, focus groups, and a formal review by hospital staff, the EWS was deployed into production use, integrating publicly available data on food access with the hospital EHR. Evaluation of EWS usage during the 2020 calendar year shows that 1,034 providers viewed the EWS, with a total of 29,165 sessions. This suggests that the EWS was successfully integrated with the EHR and is highly visible. The results also indicate that 63 (6.1%) of the providers are regular users that opt to maintain the EWS in their custom workflows, logging more than 100 EWS sessions during the year. The vendor agnostic design of the EWS supports interoperability and makes it accessible to health systems with disparate EHR vendors.

Presynaptic inhibition decreases when estrogen level rises.

The objective was to determine estrogen's influence on control of a skeletal muscle through measurements of motorneuron excitability (H:M ratio) and presynaptic inhibition (PI). Estrogen serum concentrations were measured at menses and ovulation of female subjects and compared to male controls. Data were analyzed from 12 women and 13 men reporting no history of knee ligament injury. Women reported regular menstrual cycles and no hormone-based contraceptive use for the previous year. Women were tested at menses (Time1) and ovulation (Time2). Men were tested twice, approximately 14 days apart. Analysis indicated no difference in the H:M ratio between the sexes at either time point. A significant difference for the sexes was detected in the magnitude of estrogen change (∆EST) between observations. At Time1, the male and female estrogen concentrations were not different; however, they were different at Time2, primarily due to the large rise observed in the women. A significant difference between the sexes was also seen in the magnitude of change for PI (∆PI) between observations. As with EST, the levels of PI between the sexes at Time1 were not different; however, a difference existed at Time 2. Estrogen interacts with GABA at several nervous system locations affecting inhibition of synaptic transmission. This is the first study to investigate changes in PI of a skeletal muscle between times of low and high estrogen. Improving the understanding of estrogen's influence on skeletal muscles may provide answers to why noncontact anterior cruciate ligament injuries of the knee occur more frequently in women.

Spinal and supraspinal motor control predictors of rate of torque development.

During explosive movements and potentially injurious situations, the ability to rapidly generate torque is critical. Previous research has suggested that different phases of rate of torque development (RTD) are differentiately controlled. However, the extent to which supraspinal and spinal mechanisms predict RTD at different time intervals is unknown. RTD of the plantarflexors across various phases of contraction (i.e., 0-25, 0-50, 0-100, 0-150, 0-200, and 0-250 ms) was measured in 37 participants. The following predictor variables were also measured: (a) gain of the resting soleus H-reflex recruitment curve; (b) gain of the resting homonymous post-activation depression recruitment curve; (c) gain of the GABAergic presynaptic inhibition recruitment curve; (d) the level of postsynaptic recurrent inhibition at rest; (e) level of supraspinal drive assessed by measuring V waves; and (f) the gain of the resting soleus M wave. Stepwise regression analyses were used to determine which variables significantly predicted allometrically scaled RTD. The analyses indicated that supraspinal drive was the dominant predictor of RTD across all phases. Additionally, recurrent inhibition predicted RTD in all of the time intervals except 0-150 ms. These results demonstrate the importance of supraspinal drive and recurrent inhibition to RTD.

Ubiquitination of hypoxia-inducible factor requires direct binding to the beta-domain of the von Hippel-Lindau protein.

von Hippel-Lindau (VHL) disease is a hereditary cancer syndrome that is characterized by the development of multiple vascular tumors and is caused by inactivation of the von Hippel-Lindau protein (pVHL). Here we show that pVHL, through its beta-domain, binds directly to hypoxia-inducible factor (HIF), thereby targeting HIF for ubiquitination in an alpha-domain-dependent manner. This is the first function to be ascribed to the pVHL beta-domain. Furthermore, we provide the first direct evidence that pVHL has a function analogous to that of an F-box protein, namely, to recruit substrates to a ubiquitination machine. These results strengthen the link between overaccumulation of HIF and development of VHL disease.

Biomarkers of Recent Cannabis Use in Blood, Oral Fluid and Breath.

Proving driving under the influence of cannabis (DUIC) is difficult. Establishing a biomarker of recent use to supplement behavioral observations may be a useful alternative strategy. We determined whether cannabinoid concentrations in blood, oral fluid (OF) or breath could identify use within the past 3 h-likely the period of the greatest impairment. In a randomized trial, 191 frequent (≥4/week) and occasional (<4/week) cannabis users smoked one cannabis (placebo [0.02%], or 5.9% or 13.4% Δ9-tetrahydrocannabinol [THC]) cigarette ad libitum. Blood, OF and breath samples were collected prior to and up to 6 h after smoking. Samples were analyzed for 10 cannabinoids in OF, 8 in blood and THC in breath. Frequent users had more residual THC in blood and were more likely to be categorized as 'recently used' prior to smoking; this did not occur in OF. Per se limits ranging from undetectable to 5 ng/mL THC in blood offered limited usefulness as biomarkers of recent use. Cannabinol (CBN, cutoff = 1 ng/mL) in blood offered 100% specificity but only 31.4% sensitivity, resulting in 100% positive predictive value (PPV) and 94.0% negative predictive value (NPV) at 4.3% prevalence; however, CBN may vary by cannabis chemovar. A 10 ng/mL THC cutoff in OF exhibited the overall highest performance to detect its use within 3 h (99.7% specificity, 82.4% sensitivity, 92.5% PPV and 99.2% NPV) but was still detectable in 23.2% of participants ∼4.4 h post-smoking, limiting specificity at later time points. OF THC may be a helpful indicator of recent cannabis intake, but this does not equate to impairment. Behavioral assessment of impairment is still required to determine DUIC. This study only involved cannabis inhalation, and additional research evaluating alternative routes of ingestion (i.e., oral) is needed.

The genome-enabled electronic medical record.

The integration of patient-specific genomic information into the electronic medical record (EMR) will create many opportunities to improve patient care. Key to the successful incorporation of genomic information into the EMR will be the development of laboratory information systems capable of appropriately formatting molecular diagnostic and cytogenetic findings in the EMR. Due to the lack of granular genomics-related content in existing medical vocabularies, the adoption of new standards for describing clinically significant genomic information will be an important step toward recognizing the genome-enabled EMR. Appropriate capture of patient-specific genomic results in the EMR will generate new opportunities to utilize this information in clinical decision support, including automated response to pharmacogenomic-based risks.

Visualization of molecular structures using HoloLens-based augmented reality.

Biological molecules and biologically active small molecules are complex three dimensional structures. Current flat screen monitors are limited in their ability to convey the full three dimensional characteristics of these molecules. Augmented reality devices, including the Microsoft HoloLens, offer an immersive platform to change how we interact with molecular visualizations. We describe a process to incorporate the three dimensional structures of small molecules and complex proteins into the Microsoft HoloLens using aspirin and the human leukocyte antigen (HLA) as examples. Small molecular structures can be introduced into the HoloStudio application, which provides native support for rotating, resizing and performing other interactions with these molecules. Larger molecules can be imported through the Unity gaming development platform and then Microsoft Visual Developer. The processes described here can be modified to import a wide variety of molecular structures into augmented reality systems and improve our comprehension of complex structural features.

Treatment of hairy-cell leukemia with cladribine: response, toxicity, and long-term follow-up.

PURPOSE: To analyze initial and long-term outcomes after treatment of patients with active hairy-cell leukemia (HCL) with a single cycle of cladribine (2-CdA). PATIENTS AND METHODS: Forty-nine patients with active HCL were treated with 2-CdA by continuous intravenous infusion at 0.1 mg/kg/d for a total of 7 days at the Long Island Jewish Medical Center between September 1990 and August 1992. Here we report on all patients followed-up until April 1996. RESULTS: At 3 months after treatment, complete response (CR) occurred in 37 patients (76%) and partial response (PR) occurred in 12 patients (24%), for an overall response rate of 100% (95% confidence interval, 94% to 100%). At a median follow-up of 55 months, the relapse-free survival is 80% and overall survival is 95%. Ten patients (20%) have relapsed. Of the 26 patients in whom lymphocyte phenotyping was performed, four were found to have a CD25-negative phenotype. All four of these patients had PRs only and all relapsed. Eight patients have been re-treated with 2-CdA, and all achieved at least a partial remission; two of these have already relapsed with remission durations of less than 1 year. Five second malignancies have occurred in four patients. CONCLUSION: With a median follow-up of more than 4 years, 39 patients (80%) continue in remission. Only two deaths have occurred. A CD25-negative phenotype may predict for a poorer response to 2-CdA. Patients who relapse may be re-treated with 2-CdA, but subsequent remissions may be of shorter duration. There has not been a markedly increased incidence of second malignancies or late opportunistic infections.

Fathers' hospital visits to their preterm infants as a predictor of father-infant relationship and infant development.

This short-term longitudinal study assessed the degree to which the frequency of fathers' visits with their preterm infants in the hospital was associated with the quality of ongoing and long-term fathering and infant development. Data on fathering and infant development were collected during the hospital stay, at discharge, at 8 months of age, and at 18 months of age, using both questionnaires and observational schedules. The frequency of visits was significantly correlated with more extensive and positive patterns of fathering at discharge and later periods. It was also associated with more positive perceptions of the infant, as well as with weight gain during hospitalization and psychosocial aspects of later infant development during the first 18 months. The discussion emphasized possible ways in which early paternal contact in the hospital might influence fathers, mothers, and infants. The frequency of paternal visits was high-lighted as a variable useful in predicting high-risk parenting.

Detection of antibodies to thymic tissue in human serum.

Antibodies specific to thymic tissue were detected in normal human serum by means of an indirect immunofluorescent technique. Approximately 50-88% of the total sera (33) showed positive staining, which was confined to the medullary zone primarily associated with the surface membranes of epithelial cells including Hassall's corpuscles. These observations point to the recognition by the immune-self of antigen(s) of the thymic epithelium in health, and presumably in disease.

Malignant fibrous histiocytoma: an ultrastructural study of eleven cases.

Eleven cases of malignant fibrous histiocytoma were examined electron microscopically. In six of seven cases with storiform-fascicular histologic features and in two cases with a myxoid pattern, no malignant-appearing histiocyte-like cells were identified. The neoplastic cells were fibroblasts and myofibroblasts, occasionally admixed with lymphocytes and benign-appearing histiocytes. Only in the other three cases (two pleomorphic sarcomas and one tumor with a storiform-fascicular pattern) were malignant cells with the features of histiocytes identified. The authors propose that some neoplasms with a storiform-fascicular pattern would be more accurately classified as fibrosarcomas than as histiocytomas and speculate on the possible histogenesis of those tumors that do contain histiocyte-type cells.

Vascular ring: does magnetic resonance imaging replace angiography?

The records of 21 patients who underwent operation for symptoms attributable to vascular ring were reviewed. The study covered 33 years, 1958 to 1991, and the mean follow-up was 6.8 years. The patients ranged from 7 days to 26 years old with a mean age of 2.9 years. Twenty patients were symptomatic. Symptoms were due to tracheal compression in 16 patients, esophageal compression in 2, and both causes in 2. During the first 30 years, chest roentgenography, barium swallow, and aortography constituted the diagnostic workup in the majority of the patients. During the last 3 years, magnetic resonance imaging replaced aortography. The surgical diagnosis included five variants of vascular ring. The surgical approach consisted of left thoracotomy in 19 patients and right thoracotomy in 2. These 2 had the diagnosis of right aortic arch with posterior left subclavian artery. In both instances, preoperative angiographic data determined the surgical approach. Barium swallow may be sufficient for the diagnosis of vascular ring; however, additional data are useful in determining the surgical approach. Magnetic resonance imaging can yield accurate data without subjecting the patient to the risks associated with angiography.

The effects of vision and task complexity on Hoffmann reflex gain.

Previous research demonstrates modulation of the Hoffmann reflex amplitude and gain during changes in environmental conditions. H-reflex gain (defined in this study as the ratio of H-reflex amplitude to average soleus background EMG) is considered a functional measure of reflex modulation. In this study the effects of manipulating visual input and surface stability were to investigated in 17 subjects under four experimental conditions: (1) vision-stable surface, (2) no vision-stable surface, (3) vision-unstable surface, and (4) no vision-unstable surface. In each condition, subjects performed fifteen trials of a single leg stance for 7 s. The H-reflex was electrically elicited at the end of each trial by delivering a 1 ms square wave stimulation to the tibial nerve in the popliteal online for each trial (sampling rate = 2 kHz). An analysis of variance revealed significant decreases in H-reflex gain for the visual (F1.16 = 4.71, P < 0.05) and, surface conditions (F1.16 = 7.67, P < 0.05), however there was no interaction (F1.16 = 0.48, P < 0.05), between these variables. These results suggest that supraspinal mechanisms, possibly presynaptic inhibition, modulate H-reflex gain across environmental conditions. We conclude that visual and possibly cutaneous inputs were responsible for driving presynaptic inhibition and thus decreasing H-reflex gain.

The role of cranial computed tomography in carotid surgery.

In patients who present with TIA, RIND, or CVA, the cranial CT scan can rule out other etiologies for neurologic symptoms. In addition to the clinical presentation, the CT scan allows further stratification of patients being considered for carotid endarterectomy. We propose that patients be classified as TIA (+), TIA (-), RIND (+), or CVA (-). The CT scan has defined a new subgroup of patients, TIA (+) and RIND (+)--the Silent Cerebral Infarction. Patients who are categorized as TIA (+), RIND (+), and CVA (+) (cerebral infarction on CT or by history) are at increased risk for intraoperative ischemia and postoperative neurologic deficit. As such, they should be selectively shunted based on intraoperative EEG monitoring or routinely shunted. There is a strong association between ulcerative plaque at the carotid bifurcation and cerebral infarction on CT. The CT scan is a critical diagnostic procedure in evaluating the patient with an acute neurologic event. Patients with negative CT scans are candidates for early operation. Carotid endarterectomy should generally be delayed for 4 to 6 weeks in patients with positive CT scans.

Gastroesophageal reflux in children.

Operations for the control of complicated gastroesophageal reflux in children are commonly performed procedures in large pediatric centers. The comprehensive diagnostic scheme includes radiologic and endoscopic work-up coupled with extended pH probe analysis. Medical therapy remains the principle form of management, with surgery reserved for treatment failure.

Postural control: visual and cognitive manipulations.

Numerous questions exist regarding the utilization of sensory information for postural control. Past research has established the possibility that cognitive tasks requiring visual perception may affect the processing of visual information used for postural control. The purpose of this study was two fold: (1) to investigate the effects of varying demands of visual perception and (2) to evaluate the effects of performing a cognitive task on postural control in healthy, young adults (N=30). Three posture-related dependent variables were recorded during the manipulation of two independent variables (eye movement and modality of presentation of a cognitive task). The two levels of eye movement were movement and no movement, while the three levels of modality of presentation were visual, auditory, and none. A 2x3 repeated measures ANOVA was applied to the data to investigate the presence of group differences. Significantly more variability was observed in the no cognitive condition than the visual and the auditory for medial-lateral (M--L) COP variability. Additionally, the eye movement condition revealed significantly greater M--L COP variability than the no eye movement condition. No differences were observed between the visual and auditory conditions for any dependent variable. Therefore, the greatest COP variability was observed in the eye movement and no cognitive condition. Further, an interesting relationship between the measures of COP variability and sway velocity was described.

Laryngotracheal separation and diversion for complicated esophageal atresia with intractable salivary aspiration.

Chronic salivary aspiration results in progressive pulmonary deterioration. Laryngotracheal separation and diversion were performed to prevent salivary aspiration in a patient following complex repair for esophageal atresia with distal tracheoesophageal fistula. This highly effective and potentially reversible procedure should be considered for treatment of chronic salivary aspiration in selected patients.

Unilateral pulmonary agenesis with esophageal atresia and distal tracheoesophageal fistula: report of two cases.

The combined anomalies of pulmonary agenesis with esophageal atresia and distal tracheoesopahgeal fistula are an exceedingly rare and highly lethal association. The longest survivor in the literature is 10 months. We describe two neonates with this association who underwent primary repair shortly after birth and who are alive and well at 24 and 18 months. One of these neonates also demonstrated duodenal atresia. The prime goal in the management of these patients is early protection and preservation of respiratory units. This goal is best accomplished by primary repair of the tracheoesophageal lesion, when feasible, rather than by more complex procedures.

Sutureless hemisplenectomy.

Splenic salvage following blunt injury can fail when parenchymal bleeding is uncontrollable. To define the usefulness of an argon beam coagulator for hemostasis, we used the instrument in a laboratory trial of partial splenic resection. New Zealand white rabbits, weighing 4 to 5 kg, had sharp excision of the lower half of the spleen. No sutures were used to control hemorrhage from the cut splenic surface or the hilar vessels. Hemostasis was achieved with 2 to 4 seconds of electrocoagulation delivered by a beam of argon gas. All animals survived the procedure and were in good health when killed between the fourth and sixth week following the procedure. At necropsy, the spleen was viable in all animals with no abscess or hematoma. Minimal adhesions from the treated splenic surface to the omentum were found. The scar at the cut surface was 1 mm in depth, and the histology of the remainder of the spleen was normal. In this simulated splenic injury model, argon beam coagulation was uniformly successful in achieving hemostasis. Minimal tissue destruction and lack of infection were noted. The argon beam coagulator may be useful in patients with severe splenic injuries and other situations requiring partial splenectomy.

Management of catastrophic neonatal midgut volvulus with a silo and second-look laparotomy.

The case of a neonate with midgut volvulus and severe intestinal ischemia extending from the ligament of Treitz to the midtransverse colon is presented. Management consisted of abdominal silo application at the initial exploration to obviate the adverse physiological consequences of increased intraabdominal pressure from reperfusion edema of the intestine. The majority of the intestine was salvaged, and a short segment of ileum was resected. This method of treatment resulted in optimal ventilatory status, renal function, and cardiac performance. The advantages of temporary prosthetic wound coverage in selected cases of midgut volvulus include greater physiologic stability through the avoidance of "intraabdominal hypertension" and the ability to monitor the status of the intestine at the bedside.