Mechanical Revascularization in the Era of the Field Assessment Stroke Triage for Emergency Destination (FAST-ED): A Retrospective Cohort Assessment in a Community Stroke Practice.

BACKGROUND: Endovascular mechanical revascularization has become the mainstay acute stroke management secondary to emergent large vessel occlusions. In patients who can benefit from mechanical revascularization, the ability to intervene in a timely manner directly correlates with improved outcomes. The field assessment for stroke triage (FAST-ED) prehospital triage tool, is one of many stroke severity scales designed to decrease time to diagnosis in the field and optimize patient triage to comprehensive stroke centers. It is however unclear what impact if any, this tool has on time to activation of hospital stroke intervention teams. We set out to assess the impact of the implementation of the FAST-ED triage tool on the activation of the stroke intervention team in a community stroke treatment practice. METHODS: We retrospectively reviewed institutional records for consecutive admissions with reported stroke alerts between March 2017 and September 2018, and selected patients who presented via Emergency Medical Services (EMS). The association between FAST-ED scores and impact on time to revascularization as well as the association between FAST-ED scores and the presence of emergent large vessel occlusion were analyzed. RESULTS: There was a statistically significant improvement in interventional team activation times in favor of the FAST-ED cohort, (P < .05). CONCLUSIONS: FAST-ED implementation demonstrates a statistically significant improvement on stroke team activation times for patients who are candidates for mechanical revascularization. Larger cohort analysis is needed to fully evaluate the magnitude of this effect.

Endovascular aspiration of a symptomatic free-floating common carotid artery thrombus.

Free-floating thrombi of the common carotid artery (CCA) are a very rare cause of ischemic stroke. To date, only a few reports have been described in the academic literature. Revascularization is indicated due to the risk of thromboembolic disease and hemodynamic-related stroke syndromes. Medical treatment typically includes anticoagulation and, in some circumstances, open surgical thrombectomy is an additional option. Although rarely described in the literature, endovascular thrombectomy is a viable treatment alternative in these patients.

Posterior fossa syndrome with delayed MR evidence of unilateral superior cerebellar peduncle (SCP) damage.

Posterior fossa syndrome (PFS) is a well-known sequela of midline posterior fossa tumor resection. Patients typically exhibit transient behavioral, motor, and oculomotor disturbances that resolve within a few weeks to several months after surgery. The underlying pathophysiology of PFS is not completely understood, but contemporary literature has implicated injury to the dentate nucleus and/or exiting dentatothalamocortical fiber bundles as a causative factor. The authors present a case of a young male who developed a delayed variant of PFS typified by motor deficits and demonstrated diffusion restriction in the ipsilateral superior cerebellar peduncle. Because the correlation between PFS and the superior cerebellar peduncle injury is poorly described in the literature, particularly with regard to relevant radiographic imaging, the authors of this report hope their findings will contribute to that insufficient body of evidence.

Association Between Relative Anemia and Early Functional Recovery After Severe Traumatic Brain Injury (TBI).

BACKGROUND: Severe traumatic brain injury is associated with a multi-systemic response and changes in metabolic demand. Patients requiring intracranial pressure monitoring or cerebrospinal fluid diversion, often signifies a greater severity of injury. For this group, the association between RBC transfusion, transfusion thresholds, and clinical recovery is unknown. In this study, we studied the association between transfusion and clinical recovery for severe traumatic brain injury patients requiring external ventricular drain or intracranial pressure monitor placement. METHODS: Eighty-nine patients with a primary diagnosis of traumatic brain injury requiring implantation of either an intracranial pressure monitor or external ventricular drainage device were identified. All patients were managed in a Level 1 Trauma facility by board-certified neuro-intensive care practitioners for the course of their intensive care unit duration. The correlation between transfusion and clinical recovery, defined by change in Glasgow Coma Scale was assessed. RESULTS: Thirty-four patients required surgical decompression, and 56.18 % of the cumulative cohort were transfused during admission. Overall, transfusion was not associated with significant clinical recovery (change in GCS > 3) for Hgb threshold of 7 mg/dL (<3, 29.03 vs. ≥3, 37.93 %; p = 0.49), nor for higher stratifications (8 mg/dL, p = 0.63; 9 mg/dL, p = 0.79, 10 mg/dL, p = 1). For patients who required transfusions at thresholds ≥8 mg/dL, there was a positive association with decreased length of hospitalization, [p = 0.01; <8 mg/dL: 22 (12-33), ≥8 mg/dL: 14 (7.75-20)] [median (IQR)]. Similarly, length of ICU stay was shorter for patients transfused at thresholds ≥9 mg/dL, (p = 0.02). CONCLUSIONS: From our studies, we demonstrate no significant clinical benefit associated with stratified transfusion goals; however, there was a decrease in length of hospitalization for patients with transfusion thresholds of Hgb ≥ 8 mg/dL. Larger, randomized controlled trials may be required to more accurately assess outcomes in this patient population. In patients admitted for primary severe traumatic brain injury, we demonstrate no significant clinical benefit associated with stratified transfusion goals; however, there was a noticeable decrease in length of hospitalization for patients with transfusion thresholds of Hgb ≥ 8 mg/dL. Larger, randomized controlled trials may be required to more accurately assess outcomes in this patient population.

A transcriptome approach towards understanding the development of ripening capacity in 'Bartlett' pears (Pyrus communis L.).

BACKGROUND: The capacity of European pear fruit (Pyrus communis L.) to ripen after harvest develops during the final stages of growth on the tree. The objective of this study was to characterize changes in 'Bartlett' pear fruit physico-chemical properties and transcription profiles during fruit maturation leading to attainment of ripening capacity. RESULTS: The softening response of pear fruit held for 14 days at 20 °C after harvest depended on their maturity. We identified four maturity stages: S1-failed to soften and S2- displayed partial softening (with or without ET-ethylene treatment); S3 - able to soften following ET; and S4 - able to soften without ET. Illumina sequencing and Trinity assembly generated 68,010 unigenes (mean length of 911 bp), of which 32.8 % were annotated to the RefSeq plant database. Higher numbers of differentially expressed transcripts were recorded in the S3-S4 and S1-S2 transitions (2805 and 2505 unigenes, respectively) than in the S2-S3 transition (2037 unigenes). High expression of genes putatively encoding pectin degradation enzymes in the S1-S2 transition suggests pectic oligomers may be involved as early signals triggering the transition to responsiveness to ethylene in pear fruit. Moreover, the co-expression of these genes with Exps (Expansins) suggests their collaboration in modifying cell wall polysaccharide networks that are required for fruit growth. K-means cluster analysis revealed that auxin signaling associated transcripts were enriched in cluster K6 that showed the highest gene expression at S3. AP2/EREBP (APETALA 2/ethylene response element binding protein) and bHLH (basic helix-loop-helix) transcripts were enriched in all three transition S1-S2, S2-S3, and S3-S4. Several members of Aux/IAA (Auxin/indole-3-acetic acid), ARF (Auxin response factors), and WRKY appeared to play an important role in orchestrating the S2-S3 transition. CONCLUSIONS: We identified maturity stages associated with the development of ripening capacity in 'Bartlett' pear, and described the transcription profile of fruit at these stages. Our findings suggest that auxin is essential in regulating the transition of pear fruit from being ethylene-unresponsive (S2) to ethylene-responsive (S3), resulting in fruit softening. The transcriptome will be helpful for future studies about specific developmental pathways regulating the transition to ripening.

Post-Traumatic brain injury (TBI) presenting with Guillain-Barré syndrome and elevated anti-ganglioside antibodies: a case report and review of the literature.

Guillain-Barré Syndrome (GBS) is a demyelinating polyneuropathy resulting in sensory, motor and autonomic symptoms. The severity of the disease can range from mild to severe but it is classically described as an ascending demyelinating process. Initially thought to be the sequelae of a bacterial or viral infection, the clinical symptoms of post-infective GBS can present up to 4 weeks after sentinel injury. A rarely defined post-surgical GBS has been since described after major cranial, cardiothoracic and gastro-intestinal surgery. Post traumatic GBS is an even more unusual presentation with very few cases reported in contemporary academic literature. We present a case of GBS presenting two weeks after non-operative traumatic brain injury (TBI) and a review of the literature.

Ex vivo studies for the passive transdermal delivery of low-dose naltrexone from a cream; detection of naltrexone and its active metabolite, 6ß-naltrexol, using a novel LC Q-ToF MS assay.

Naltrexone (NTX) is a long-acting opiate antagonist. Low-dose naltrexone (LDN) therapy has shown promising results in the treatment of several autoimmune disorders. Our aim was to formulate NTX into a cream for the delivery of LDN and develop an analytical technique for the quantification of NTX and its active metabolite 6-ß-naltrexol (NTXol) during transdermal diffusion cell permeation studies. A 1% w/w NTX cream was formulated and drug permeation was examined over 24 h using static Franz diffusion cells mounted with pig skin. A Liquid Chromatography Quadrupole-Time of Flight Mass Spectrometry (LC-MS Q-ToF) method was developed for the detection of NTX and NTXol in the receptor solution, skin membrane and residual cream on the donor chamber after completion of the diffusion studies. The cream formulation exhibited steady state release of NTX over 24 h after an initial lag time of 2.74 h. The bioconversion of NTX to NTXol in the skin membrane was 1.1%. It was concluded that the cream may be an effective formulation for the sustained transdermal delivery of LDN. The novel LC Q-ToF MS method allowed the accurate measurement of NTX and NTXol levels across the diffusion cell assemblies and the quantification of NTX metabolism in the skin.

The PAX LC Trial: A Decentralized, Phase 2, Randomized, Double-Blind Study of Nirmatrelvir/Ritonavir Compared with Placebo/Ritonavir for Long COVID.

BACKGROUND: Individuals with long COVID lack evidence-based treatments and have difficulty participating in traditional site-based trials. Our digital, decentralized trial investigates the efficacy and safety of nirmatrelvir/ritonavir, targeting viral persistence as a potential cause of long COVID. METHODS: The PAX LC trial (NCT05668091) is a Phase 2, 1:1 randomized, double-blind, superiority, placebo-controlled trial in 100 community-dwelling, highly symptomatic adult participants with long COVID residing in the 48 contiguous US states to determine the efficacy, safety, and tolerability of 15 days of nirmatrelvir/ritonavir compared with placebo/ritonavir. Participants are recruited via patient groups, cultural ambassadors, and social media platforms. Medical records are reviewed through a platform facilitating participant-mediated data acquisition from electronic health records nationwide. During the drug treatment, participants complete daily digital diaries using a web-based application. Blood draws for eligibility and safety assessments are conducted at or near participants' homes. The study drug is shipped directly to participants' homes. The primary endpoint is the PROMIS-29 Physical Health Summary Score difference between baseline and Day 28, evaluated by a mixed model repeated measure analysis. Secondary endpoints include PROMIS-29 (Mental Health Summary Score and all items), Modified GSQ-30 with supplemental symptoms questionnaire, COVID Core Outcome Measures for Recovery, EQ-5D-5L (Utility Score and all items), PGIS 1 and 2, PGIC 1 and 2, and healthcare utilization. The trial incorporates immunophenotyping to identify long COVID biomarkers and treatment responders. CONCLUSION: The PAX LC trial uses a novel decentralized design and a participant-centric approach to test a 15-day regimen of nirmatrelvir/ritonavir for long COVID.

Time to First Shunt Failure in Pediatric Patients over 1 Year Old: A 10-Year Retrospective Study.

Studies comparing alternatives to ventriculoperitoneal (VP) shunting for treatment of hydrocephalus have often relied upon data from an earlier era that may not be representative of contemporary shunt survival outcomes. We sought to determine the shunt survival rate of our cohort and compare our results to previously published shunt survival and endoscopic third ventriculostomy (ETV) success rates. We identified 95 patients between 1 and 18 years of age, who underwent initial VP shunt placement between January 2001 and December 2010. Our study shows a shunt survival rate of 85% at 6 months and 79% at 2 years, for initial shunts in pediatric patients over 1 year of age in this cohort. The overall infection rate was 3%. This compares favorably with published success rates of ETV at similar time points as well as with the rate of infection. This suggests that ventricular shunting remains a viable alternative to ETV in the older child.

Transcriptome analyses of early cucumber fruit growth identifies distinct gene modules associated with phases of development.

UNLABELLED: ABBACKGROUND: Early stages of fruit development from initial set through exponential growth are critical determinants of size and yield, however, there has been little detailed analysis of this phase of development. In this study we combined morphological analysis with 454 pyrosequencing to study transcript level changes occurring in young cucumber fruit at five ages from anthesis through the end of exponential growth. RESULTS: The fruit samples produced 1.13 million ESTs which were assembled into 27,859 contigs with a mean length of 834 base pairs and a mean of 67 reads per contig. All contigs were mapped to the cucumber genome. Principal component analysis separated the fruit ages into three groups corresponding with cell division/pre-exponential growth (0 and 4 days post pollination (dpp)), peak exponential expansion (8dpp), and late/post-exponential expansion stages of growth (12 and 16 dpp). Transcripts predominantly expressed at 0 and 4 dpp included homologs of histones, cyclins, and plastid and photosynthesis related genes. The group of genes with peak transcript levels at 8dpp included cytoskeleton, cell wall, lipid metabolism and phloem related proteins. This group was also dominated by genes with unknown function or without known homologs outside of cucurbits. A second shift in transcript profile was observed at 12-16dpp, which was characterized by abiotic and biotic stress related genes and significant enrichment for transcription factor gene homologs, including many associated with stress response and development. CONCLUSIONS: The transcriptome data coupled with morphological analyses provide an informative picture of early fruit development. Progressive waves of transcript abundance were associated with cell division, development of photosynthetic capacity, cell expansion and fruit growth, phloem activity, protection of the fruit surface, and finally transition away from fruit growth toward a stage of enhanced stress responses. These results suggest that the interval between expansive growth and ripening includes further developmental differentiation with an emphasis on defense. The increased transcript levels of cucurbit-specific genes during the exponential growth stage may indicate unique factors contributing to rapid growth in cucurbits.

An mRNA blueprint for C4 photosynthesis derived from comparative transcriptomics of closely related C3 and C4 species.

C(4) photosynthesis involves alterations to the biochemistry, cell biology, and development of leaves. Together, these modifications increase the efficiency of photosynthesis, and despite the apparent complexity of the pathway, it has evolved at least 45 times independently within the angiosperms. To provide insight into the extent to which gene expression is altered between C(3) and C(4) leaves, and to identify candidates associated with the C(4) pathway, we used massively parallel mRNA sequencing of closely related C(3) (Cleome spinosa) and C(4) (Cleome gynandra) species. Gene annotation was facilitated by the phylogenetic proximity of Cleome and Arabidopsis (Arabidopsis thaliana). Up to 603 transcripts differ in abundance between these C(3) and C(4) leaves. These include 17 transcription factors, putative transport proteins, as well as genes that in Arabidopsis are implicated in chloroplast movement and expansion, plasmodesmatal connectivity, and cell wall modification. These are all characteristics known to alter in a C(4) leaf but that previously had remained undefined at the molecular level. We also document large shifts in overall transcription profiles for selected functional classes. Our approach defines the extent to which transcript abundance in these C(3) and C(4) leaves differs, provides a blueprint for the NAD-malic enzyme C(4) pathway operating in a dicotyledon, and furthermore identifies potential regulators. We anticipate that comparative transcriptomics of closely related species will provide deep insight into the evolution of other complex traits.

Association between biomechanical parameters and concussion in helmeted collisions in American football: a review of the literature.

OBJECT: The authors' goal was to better define the relationship between biomechanical parameters of a helmeted collision and the likelihood of concussion. METHODS: The English-language literature was reviewed in search of scholarly articles describing the rotational and translational accelerations observed during all monitored impact conditions that resulted in concussion at all levels of American football. RESULTS: High school players who suffer concussion experience an average of 93.9g of translational acceleration (TA) and 6505.2 rad/s(2) of rotational acceleration (RA). College athletes experience an average of 118.4g of TA and 5311.6 rad/s(2) of RA. While approximately 3% of collisions are associated with TAs greater than the mean TA associated with concussion, only about 0.02% of collisions actually result in a concussion. Associated variables that determine whether a player who experiences a severe collision also experiences a concussion remain hypothetical at present. CONCLUSIONS: The ability to reliably predict the incidence of concussion based purely on biomechanical data remains elusive. This study provides novel, important information that helps to quantify the relative insignificance of biomechanical parameters in prediction of concussion risk. Further research will be necessary to better define other factors that predispose to concussion.

Neurosurgical checklists: a review.

Morbidity due to avoidable medical errors is a crippling reality intrinsic to health care. In particular, iatrogenic surgical errors lead to significant morbidity, decreased quality of life, and attendant costs. In recent decades there has been an increased focus on health care quality improvement, with a concomitant focus on mitigating avoidable medical errors. The most notable tool developed to this end is the surgical checklist. Checklists have been implemented in various operating rooms internationally, with overwhelmingly positive results. Comparatively, the field of neurosurgery has only minimally addressed the utility of checklists as a health care improvement measure. Literature on the use of checklists in this field has been sparse. Considering the widespread efficacy of this tool in other fields, the authors seek to raise neurosurgical awareness regarding checklists by reviewing the current literature.

A structured approach to EHR surveillance of diagnostic error in acute care: an exploratory analysis of two institutionally-defined case cohorts.

OBJECTIVES: To test a structured electronic health record (EHR) case review process to identify diagnostic errors (DE) and diagnostic process failures (DPFs) in acute care. METHODS: We adapted validated tools (Safer Dx, Diagnostic Error Evaluation Research [DEER] Taxonomy) to assess the diagnostic process during the hospital encounter and categorized 13 postulated e-triggers. We created two test cohorts of all preventable cases (n=28) and an equal number of randomly sampled non-preventable cases (n=28) from 365 adult general medicine patients who expired and underwent our institution's mortality case review process. After excluding patients with a length of stay of more than one month, each case was reviewed by two blinded clinicians trained in our process and by an expert panel. Inter-rater reliability was assessed. We compared the frequency of DE contributing to death in both cohorts, as well as mean DPFs and e-triggers for DE positive and negative cases within each cohort. RESULTS: Twenty-seven (96.4%) preventable and 24 (85.7%) non-preventable cases underwent our review process. Inter-rater reliability was moderate between individual reviewers (Cohen's kappa 0.41) and substantial with the expert panel (Cohen's kappa 0.74). The frequency of DE contributing to death was significantly higher for the preventable compared to the non-preventable cohort (56% vs. 17%, OR 6.25 [1.68, 23.27], p<0.01). Mean DPFs and e-triggers were significantly and non-significantly higher for DE positive compared to DE negative cases in each cohort, respectively. CONCLUSIONS: We observed substantial agreement among final consensus and expert panel reviews using our structured EHR case review process. DEs contributing to death associated with DPFs were identified in institutionally designated preventable and non-preventable cases. While e-triggers may be useful for discriminating DE positive from DE negative cases, larger studies are required for validation. Our approach has potential to augment institutional mortality case review processes with respect to DE surveillance.

Colonic Migration of a Nephroureteral Stent Through a Colovesical Fistula.

Description We describe a case of a patient with a two-year history of prostate cancer who underwent placement of nephroureteral stents. He subsequently presented to the hospital with complications from prolonged retention of the stents, which ultimately lead to a secondary diagnosis of adenocarcinoma of the rectum. A colonoscopy performed approximately two weeks after a bilateral nephroureteral tube exchange demonstrated what was believed to be locoregional metastatic disease and a fistulous connection with the distal nephroureteral stents. Radiographic features of this complication are discussed together with proper management and possible complications of distal nephroureteral stents. Both nephroureteral stents were explanted, and nephrostomy catheters were sequentially replaced to allow for healing of the fistula.

Research, Clinical, and Sociological Aspects of Autism.

The concept of autism continues to evolve. Not only have the central diagnostic criteria that define autism evolved but understanding of the label and how autism is viewed in research, clinical and sociological terms has also changed. Several key issues have emerged in relation to research, clinical and sociological aspects of autism. Shifts in research focus to encompass the massive heterogeneity covered under the label and appreciation that autism rarely exists in a diagnostic vacuum have brought about new questions and challenges. Diagnostic changes, increasing moves towards early diagnosis and intervention, and a greater appreciation of autism in girls and women and into adulthood and old age have similarly impacted on autism in the clinic. Discussions about autism in socio-political terms have also increased, as exemplified by the rise of ideas such as neurodiversity and an increasingly vocal dialogue with those diagnosed on the autism spectrum. Such changes are to be welcomed, but at the same time bring with them new challenges. Those changes also offer an insight into what might be further to come for the label of autism.

Analyzing diagnostic errors in the acute setting: a process-driven approach.

OBJECTIVES: We describe an approach for analyzing failures in diagnostic processes in a small, enriched cohort of general medicine patients who expired during hospitalization and experienced medical error. Our objective was to delineate a systematic strategy for identifying frequent and significant failures in the diagnostic process to inform strategies for preventing adverse events due to diagnostic error. METHODS: Two clinicians independently reviewed detailed records of purposively sampled cases identified from established institutional case review forums and assessed the likelihood of diagnostic error using the Safer Dx instrument. Each reviewer used the modified Diagnostic Error Evaluation and Research (DEER) taxonomy, revised for acute care (41 possible failure points across six process dimensions), to characterize the frequency of failure points (FPs) and significant FPs in the diagnostic process. RESULTS: Of 166 cases with medical error, 16 were sampled: 13 (81.3%) had one or more diagnostic error(s), and a total of 113 FPs and 30 significant FPs were identified. A majority of significant FPs (63.3%) occurred in "Diagnostic Information and Patient Follow-up" and "Patient and Provider Encounter and Initial Assessment" process dimensions. Fourteen (87.5%) cases had a significant FP in at least one of these dimensions. CONCLUSIONS: Failures in the diagnostic process occurred across multiple dimensions in our purposively sampled cohort. A systematic analytic approach incorporating the modified DEER taxonomy, revised for acute care, offered critical insights into key failures in the diagnostic process that could serve as potential targets for preventative interventions.

The sea lamprey Petromyzon marinus genome reveals the early origin of several chemosensory receptor families in the vertebrate lineage.

BACKGROUND: In gnathostomes, chemosensory receptors (CR) expressed in olfactory epithelia are encoded by evolutionarily dynamic gene families encoding odorant receptors (OR), trace amine-associated receptors (TAAR), V1Rs and V2Rs. A limited number of OR-like sequences have been found in invertebrate chordate genomes. Whether these gene families arose in basal or advanced vertebrates has not been resolved because these families have not been examined systematically in agnathan genomes. RESULTS: Petromyzon is the only extant jawless vertebrate whose genome has been sequenced. Known to be exquisitely sensitive to several classes of odorants, lampreys detect fewer amino acids and steroids than teleosts. This reduced number of detectable odorants is indicative of reduced numbers of CR gene families or a reduced number of genes within CR families, or both, in the sea lamprey. In the lamprey genome we identified a repertoire of 59 intact single-exon CR genes, including 27 OR, 28 TAAR, and four V1R-like genes. These three CR families were expressed in the olfactory organ of both parasitic and adult life stages. CONCLUSION: An extensive search in the lamprey genome failed to identify potential orthologs or pseudogenes of the multi-exon V2R family that is greatly expanded in teleost genomes, but did find intact calcium-sensing receptors (CASR) and intact metabotropic glutamate receptors (MGR). We conclude that OR and V1R arose in chordates after the cephalochordate-urochordate split, but before the diversification of jawed and jawless vertebrates. The advent and diversification of V2R genes from glutamate receptor-family G protein-coupled receptors, most likely the CASR, occurred after the agnathan-gnathostome divergence.

Development and reproducibility of a novel high-performance liquid-chromatography monolithic column method for the detection and quantification of trans-indolyl-3-acryloylglycine in human urine.

Elevated levels of trans-indolyl-3-acryloylglycine (IAcrGly) have been reported in the urine of people with various conditions including pervasive developmental disorders (PDDs) such as autism and Asperger syndrome. Reversed-phase high-performance liquid chromatography with ultra-violet detection using traditional particle silica-based columns subsequent to solid-phase extraction (SPE) has been the preferred assay method; requiring long analytical run times, high flow rates and high solvent usage. Recent developments in monolithic HPLC column technology facilitated the development of a novel analytical method, for the detection and quantification of urinary IAcrGly. The revised method eliminates the requirement for SPE pre-treatment, reduces sample run-time and decreases solvent volumes. Five urine samples from people diagnosed with PDD were run in quadruplicate to test the intra- and inter-day reliability of the new method based on retention time, peak area and peak height for IAcrGly. Detection was by UV with IAcrGly confirmation by MS/MS-MS. Relative standard deviations showed significant improvement with the new method for all parameters. The new method represents a major advancement in the detection and quantification of IAcrGly by reducing time and cost of analysis whilst improving detection limits and reproducibility.