Candida Dublinensis Meningitis in an Immunocompetent Host: A Case Report and Review of the Literature.

Objectives: This study presents a case of Candida dubliniensis meningitis in an immunocompetent injection drug user and provides a literature review of CNS infections related to C dubliniensis. Methods: A 32-year-old man with a history of opioid use disorder presented with seizures and underwent extensive diagnostic evaluations, including imaging, lumbar puncture, and tissue biopsies. Treatment consisted of antifungal therapy and placement of ventriculoperitoneal shunt (VPS). Results: C dublinensis meningitis was identified on culture from a posterior fossa arachnoid sample. The patient demonstrated leptomeningeal enhancement on imaging, which resolved following 20 weeks of fluconazole. The development of hydrocephalus necessitated placement of VPS. Additional published cases of C dublinensis meningitis revealed varying presentations, diagnostic methods, and treatment regimens. Discussion: C dublinensis meningitis is a rare condition affecting both immunocompromised and immunocompetent individuals, particularly those with intravenous drug use. The diagnosis can be challenging, often requiring repeat lumbar punctures, extensive CSF sampling, or meningeal biopsy. Treatment involves a combination of antifungal agents, such as amphotericin B and fluconazole. Intracranial hypertension and hydrocephalus may necessitate surgical intervention. In conclusion, C dublinensis meningitis should be considered as a potential etiology of meningitis, particularly in those with a history of injection drug use.

Mechanism of Action and Translational Potential of (S)-Meclizine in Preemptive Prophylaxis Against Stroke.

BACKGROUND: Mild chemical inhibition of mitochondrial respiration can confer resilience against a subsequent stroke or myocardial infarction, also known as preconditioning. However, the lack of chemicals that can safely inhibit mitochondrial respiration has impeded the clinical translation of the preconditioning concept. We previously showed that meclizine, an over-the-counter antivertigo drug, can toggle metabolism from mitochondrial respiration toward glycolysis and protect against ischemia-reperfusion injury in the brain, heart, and kidney. Here, we examine the mechanism of action of meclizine and report the efficacy and improved safety of the (S) enantiomer. METHODS: We determined the anoxic depolarization latency, tissue and neurological outcomes, and glucose uptake using micro-positron emission tomography after transient middle cerebral artery occlusion in mice pretreated (-17 and -3 hours) with either vehicle or meclizine. To exclude a direct effect on tissue excitability, we also examined spreading depression susceptibility. Furthermore, we accomplished the chiral synthesis of (R)- and (S)-meclizine and compared their effects on oxygen consumption and histamine H1 receptor binding along with their brain concentrations. RESULTS: Micro-positron emission tomography showed meclizine increases glucose uptake in the ischemic penumbra, providing the first in vivo evidence that the neuroprotective effect of meclizine indeed stems from its ability to toggle metabolism toward glycolysis. Consistent with reduced reliance on oxidative phosphorylation to sustain the metabolism, meclizine delayed anoxic depolarization onset after middle cerebral artery occlusion. Moreover, the (S) enantiomer showed reduced H1 receptor binding, a dose-limiting side effect for the racemate, but retained its effect on mitochondrial respiration. (S)-meclizine was at least as efficacious as the racemate in delaying anoxic depolarization onset and decreasing infarct volumes after middle cerebral artery occlusion. CONCLUSIONS: Our data identify (S)-meclizine as a promising new drug candidate with high translational potential as a chemical preconditioning agent for preemptive prophylaxis in patients with high imminent stroke or myocardial infarction risk.

Xylanase and beta-glucanase improve performance parameters and footpad dermatitis and modulate intestinal microbiota in broilers under an Eimeria challenge.

Coccidiosis is an enteric disease of poultry worldwide that compromises gut health and growth performance. The current research investigated the effects of 2 doses of a multienzyme preparation on broilers' performance, gut health, and footpad dermatitis (FPD) under an Eimeria challenge. A total of 512 mixed-sex day-old chicks (Cobb 500) were randomly allocated to 4 treatments of 8 replicates. Treatments were: 1) nonchallenged control (NC); 2) NC + Eimeria challenge (CC); 3) CC + recommended level of xylanase and glucanase (XG, 100 g/t feed [on top]); 4) CC + double XG (2XG, 200 g/t feed). Eimeria spp. vaccine strains were gavaged on d 9 to induce coccidiosis in chickens. Performance parameters were evaluated during starter, grower, and finisher phases, and 4 birds per pen were euthanized on d 16 for sampling, FPD was scored on d 35, and litter moisture was analyzed on d 17 and 35. The data were analyzed using 1-way ANOVA with Tukey's test to separate means, and Kruskal-Wallis test was used for non-normally distributed parameters. The results showed that the Eimeria challenge was successful based on reduced weight gain and feed intake during grower phase, and higher FITC-d concentration, lesion score (female), and oocyst counts (d 14) in CC group compared to N.C. group, while XG and 2XG increased (P < 0.001) weight gain and improved FCR compared to CC and NC groups during finisher phase. The addition of X.G. and 2XG decreased litter moisture (P = 0.003) and FPD (P < 0.001) in challenged broilers compared to the N.C. group (d 35). Supplementing XG and 2XG reestablished the population of Lactobacillus in the cecum of challenged birds to an intermediate level between the NC and CC groups (P > 0.05). The inclusion of XG tended to increase the expression of Junctional adhesion molecule 2 (JAM2), which was not different from CC and NC groups (P > 0.05). In conclusion, the combination of xylanase and glucanase (Natugrain TS) improved the performance and modulated jejunal microbiota of broilers under mild Eimeria challenge.

Buffered formic acid and a monoglyceride blend improve performance and modulate gut bacteria and immunity gene expression in broilers under necrotic enteritis challenge.

Due to the removal of antibiotics from animal feed, alternatives have been sought to control necrotic enteritis (NE) in broilers. The current study investigated the effects of buffered formic acid (Amasil NA) and monoglycerides of short- and medium-chain fatty acids (Balangut LS P) on the performance and gut health of broilers challenged with NE. A total of 816 as-hatched 1-d-old chicks (Cobb 500) were randomly assigned to 6 treatments with 8 replicates. Treatments were: T1) nonchallenged control; T2) NE challenged control; T3) Amasil NA (challenge plus Amasil NA, 0.3% throughout all phases); T4) Balangut LS P (challenge plus Balangut LS P, 0.5%, 0.3%, and 0.2% in the starter, grower and finisher phases, respectively; T5) Combined (challenge plus combination of T3 and T4); T6) Antibiotic (challenge plus Zn bacitracin, 0.05 % throughout all phases). Birds were orally gavaged with live Eimeria vaccine species (d 9) and with Clostridium perfringens (d 14 and 15). On d 16, birds were sampled to evaluate gut permeability, microbiota, and mRNA abundance in the jejunum. The data were analyzed in JMP software using one-way ANOVA with Tukey's test to separate means, and Kruskal-Wallis test was used for non-normally-distributed parameters. Results showed that Balangut LS P decreased (P<0.05) feed conversion ratio compared to nonchallenged ones at the end of the study. Balangut LS P reduced (P < 0.05) the level of cecal Bacteriods compared to nonchallenged group, whereas Amasil NA shifted the levels of ileal Bifidobacteria, Enterobacteriaceae, and Lactobacillus towards nonchallenged control (P > 0.05). NE challenge upregulated (P < 0.001) the expression of IL-21R, zeta chain of T cell receptor (ZAP70), and dual specificity phosphatase 4 (DUSP4) compared to nonchallenged birds, whereas Balangut LS P showed an intermediate (P > 0.05) expression pattern of these genes towards nonchallenged and antibiotic groups. In conclusion, combination of Balangut LS P and Amasil NA has the potential to be used as an additive to improve the performance and gut health of broiler chickens, especially under challenging conditions such as NE infections.

Strokes in Patients With Injection Drug Use and Tricuspid Valve Endocarditis - A Case Series.

Research Design: In this study, we describe patients from a tertiary care safety-net hospital endocarditis registry with tricuspid valve infective endocarditis (TVIE), and concomitant acute or subacute ischemic stroke predominantly associated with injection drug use (IDU). We retrospectively obtained data pertinent to neurologic examinations, history of injection drug use (IDU), blood cultures, transthoracic/transesophageal echocardiography (TTE/TEE), neuroimaging, and Modified Rankin Scale (mRS) scores at discharge. Only those patients with bacteremia, tricuspid valve vegetations, and neuroimaging consistent with acute to subacute ischemic infarction and microhemorrhages in two cases were included in this series. Results: Of 188 patients in the registry, 66 patients had TVIE and 10 of these were complicated by ischemic stroke. Neurologic symptoms were largely non-specific, eight patients had altered mental status and only 3 had focal deficits. Nine cases were associated with IDU. Two patients had evidence of a patent foramen ovale on echocardiography. Blood cultures grew S. aureus species in 9 of the patients, all associated with IDU. Three patients died during hospitalization. The mRS score at discharge for survivors ranged 0-4. Conclusions: Patients with strokes from TVIE had heterogeneous presentations and putative mechanisms. We noted that robust neuroimaging is lacking for patients with TVIE from IDU and that such patients may benefit from neuroimaging as a screen for strokes to assist peri-operative management. Further inquiry is needed to elucidate stroke mechanisms in these patients.

Splanchnic vein thrombosis in acute pancreatitis: a review of treatment indications, methods, and outcomes in a single institution.

BACKGROUND: Splanchnic vein thrombosis (SVT) is a well-recognized complication of acute pancreatitis. The question of whether or not to treat SVT with systemic therapeutic anticoagulation (STA) remains to be seen. The universal use of anticoagulation may lead to an increased risk of bleeding complications associated with acute pancreatitis. Literature on this subject is sparse and there is no clear guideline on how to treat SVT. Our research demonstrates local practice where therapeutic anticoagulation in SVT varies. METHODS: A retrospective review of patients presenting with acute pancreatitis admitted over a five-year period to a single tertiary hospital with splanchnic vein thrombosis was performed. RESULTS: Of the 1408 patients admitted with acute pancreatitis, 42 were diagnosed with splanchnic vein thrombosis, with a male dominance of 34 (81%). A total of 25 patients received anticoagulation. The use of anticoagulation was dependent on the location of the thrombus, P < 0.01. Anticoagulation use was most common in cases of combination mesenteric, splenic, and portal vein thrombus (100%), isolated mesenteric vein (100%), isolated portal vein (89%), combination portal and splenic vein (87%), and combination mesenteric and splenic vein (75%). The rate of anticoagulation use was lowest in isolated splenic vein thrombus (23%). CONCLUSION: The early commencement of STA in patients with acute pancreatitis and triple-vessel SVT or with portal vein involvement is supported by our data. Isolated splenic vein thrombus does not require systemic therapy. Further research is needed to establish a clear clinical guideline.

Sex proportion as a covariate increases the statistical test power in growth performance based experiments using as-hatched broilers.

The availability of sexed day-old broiler chicks is becoming an issue as feather sexing is no longer possible. This has great implications for broiler researchers as the use of randomly distributed mixed-sex birds may result in a greater between-pen variation and thus less statistical power than the use of single-sex birds. The objective of this study was to evaluate the effect of including sex proportion as a covariate in an analysis of covariance (ANCOVA) on the statistical power compared to analysis of variance (ANOVA) where sex was not considered. The statistical parameters examined include mean square error (MSE), the F-statistic, model fit, model significance and observed power. A total of 4 separate experiments that used mixed-sex broilers with unequal numbers of male and female birds per pen were conducted during which performance of the birds was measured. The male % in each pen was recorded during each experiment and corrected for mortality. The performance results were analysed by ANOVA and the statistical parameters were then compared to ANCOVA where sex proportion was included as a covariate. The results showed that a set of assumptions first needed to be met to run ANCOVA. In addition, if the ANOVA results show a high level of model significance and power, then ANCOVA may not be necessary. In other circumstances where the assumptions are met and model significance and observed power are low, the inclusion of sex proportion as a covariate in the analysis will help to reduce MSE, increase the F-statistic value and improve the model significance, model fit and observed power. Therefore, it is suggested that sex proportion should be considered as a covariate in ANCOVA to improve statistical power in nutritional experiments when male and female broilers are unequally and randomly distributed in pens.

Identification and prediction of Parkinson's disease subtypes and progression using machine learning in two cohorts.

The clinical manifestations of Parkinson's disease (PD) are characterized by heterogeneity in age at onset, disease duration, rate of progression, and the constellation of motor versus non-motor features. There is an unmet need for the characterization of distinct disease subtypes as well as improved, individualized predictions of the disease course. We used unsupervised and supervised machine learning methods on comprehensive, longitudinal clinical data from the Parkinson's Disease Progression Marker Initiative (n = 294 cases) to identify patient subtypes and to predict disease progression. The resulting models were validated in an independent, clinically well-characterized cohort from the Parkinson's Disease Biomarker Program (n = 263 cases). Our analysis distinguished three distinct disease subtypes with highly predictable progression rates, corresponding to slow, moderate, and fast disease progression. We achieved highly accurate projections of disease progression 5 years after initial diagnosis with an average area under the curve (AUC) of 0.92 (95% CI: 0.95 ± 0.01) for the slower progressing group (PDvec1), 0.87 ± 0.03 for moderate progressors, and 0.95 ± 0.02 for the fast-progressing group (PDvec3). We identified serum neurofilament light as a significant indicator of fast disease progression among other key biomarkers of interest. We replicated these findings in an independent cohort, released the analytical code, and developed models in an open science manner. Our data-driven study provides insights to deconstruct PD heterogeneity. This approach could have immediate implications for clinical trials by improving the detection of significant clinical outcomes. We anticipate that machine learning models will improve patient counseling, clinical trial design, and ultimately individualized patient care.

Persistent coagulopathy after gunshot traumatic brain injury: the importance of INR and the SPIN score.

INTRODUCTION: Penetrating ballistic brain injury (gunshot traumatic brain injury or GTBI) is associated with a high mortality. Admission Glascow Coma Scale (GCS), injury severity score and neurological findings, cardiopulmonary instability, coagulopathy and radiological finding such as bullet trajectory and mass effect are shown to predict survival after GTBI. We aimed to examine the dynamics of the observed coagulopathy and its association with outcome. METHODS: In this single-centered retrospective cohort study, we examined 88 patients with GTBI between 2015 and 2021. Variables analyzed include patient age; temperature, hemodynamic and respiratory variables, admission Glasgow Coma Scale (GCS); injury severity score (ISS); head abbreviated injury scale (AIS); Marshall, Rotterdam, SPIN and Baylor scores, and laboratory data including PTT, INR and platelet count. Receiver operating characteristic analysis was conducted to evaluate the performance of the predictive models. RESULTS: The average age of our sample was 28.5 years and a majority were male subjects (92%). Fifty-four (62%) of the patients survived to discharge. The GCS score, as well as the motor, verbal, and eye-opening sub-scores were higher in survivors (P < 0.001). As was expected, radiologic findings including the Marshall and Rotterdam Scores were also associated with survival (P < 0.001). Although the ISS and Head AIS scores were higher (P < 0.001), extracranial injuries were not more prevalent in non-survivors (P= 0.567). Non-survivors had lower platelet counts and elevated PTT and INR (P < 0.001) on admission. PTT normalized within 24 h but INR continued to increase in non-survivors. SPIN score, which includes INR, was a better predictor for mortality than Rotterdam, Marshall, and Baylor etc. CONCLUSION: Progressively increasing INR after GTBI is associated with poor outcome and may indicate consumption coagulopathy from activation of the extrinsic pathway of coagulation and metabolic derangements that are triggered and sustained by the brain injury. The SPIN score, which incorporates INR as a major survival score component, outperforms other available prediction models for predicting outcome after GTBI.

Splanchnic venous thrombosis: aetiologies and a review of the literature.

BACKGROUND: Splanchnic vein thrombosis (SVT) is an uncommon yet potentially life-threatening manifestation of venous thromboembolism. The aim of this study was to present a retrospective analysis of a cohort of Western Australian patients diagnosed with SVT on imaging study, and a review of the literature surrounding the aetiology, location, anticoagulation treatment and outcomes of SVT. METHODS: All patients diagnosed with SVT over a five-year period from 2015 to 2020 in three tertiary hospitals in Western Australia were identified by using an electronic search engine of imaging reports. Collected data included patient demographics and co-morbidity, presentation data, location of thrombus, aetiology of thrombus, treatment with anti-coagulation, length of stay and outcome data including mortality. RESULTS: A total of 164 patients met inclusion criteria. The 90-day mortality was 20.1%; 64% of whom were those with portal vein thrombosis. Aetiology was grouped into haematological conditions (4 patients), non-haematological conditions (130 patients), a combination of factors (17 patients) and idiopathic (13 patients). The majority of deaths were due to malignancy, severe pancreatitis or decompensated liver cirrhosis. CONCLUSION: Whilst the prevalence of SVT is rising with the increase in accessibility to radiological studies, it remains a diagnostic and therapeutic challenge for clinicians. With no consensus guidelines available to direct treatment, the management of patients with SVT should be individualized and considered carefully. The potential complications of venous thrombosis, SVT recurrence or extension and the risk of bleeding need to be evaluated before the commencement of anticoagulation therapy.

Intestinal changes and immune responses during Clostridium perfringens-induced necrotic enteritis in broiler chickens.

Clostridium perfringens-induced necrotic enteritis (NE) is an economically important disease of broiler chickens. The present study evaluated the effect of C. perfringens on the intestinal histomorphometry, enteric microbial colonization, and host immune responses using 3 experimental NE reproduction methods. The experimental groups consisted of 1) unchallenged Control diet (corn-soybean meal), 2) Control diet + Eimera inoculation at d 11 followed by C. perfringens challenge at d 15 (ECp), 3) Wheat-based diet + C. perfringens challenge (WCp), and 4) Wheat-based diet + Eimeria inoculation followed by C. perfringens challenge (WECp). The results showed that chickens receiving ECp and WECp had reduced (P < 0.05) bird performance coupled with enteric gross lesions and epithelial damage at d 17 and 24 of age compared to unchallenged control birds. These ECp and WECp administered birds also had increased (P < 0.05) ileal colonization by clostridia and E. coli at d 17 and 24, while the resident Lactobacillus counts were reduced (P < 0.05) at d 24 of age. Furthermore, at d 24, jejunal transcription of IL-6, IL-10, annexin-A1 and IL-2 genes was upregulated (P < 0.05) in the ECp group, whereas the transcription of TNF receptor associated factor (TRAF)-3 gene was increased (P < 0.05) in WECp treated birds when compared to unchallenged control group. Additionally, stimulation of chicken splenocytes and cecal tonsilocytes with virulent C. perfringens bacilli or their secretory proteins resulted in a higher (P < 0.05) frequency of T cells and their upregulation of MHC-II molecule, as determined by flow cytometry. These findings suggest that C. perfringens, while inducing epithelial damage and changes in microbiota, can also trigger host immune responses. Furthermore, NE reproduction methods using coccidia with or without the wheat-based dietary predisposition seem to facilitate an optimal NE reproduction in broiler chickens and thus, may provide better avenues for future C. perfringens research.

The effect of comorbidity on early clinical decision making in acute mesenteric ischemia.

INTRODUCTION: Acute mesenteric ischemia (AMI) is a surgical emergency with a high mortality and morbidity rate. Prompt diagnosis and early surgical management are the cornerstones of management. In certain patients, however, treatment is futile and early palliative care, lessens patient, and family distress. The aim of this study was to investigate factors, focusing on patient comorbidity, that may predict futility of treatment and hence, guide clinicians in their decision making. PATIENTS AND METHODS: Consecutive adult patients with AMI diagnosed on imaging were reviewed for demographics, comorbidity, imaging, and biochemical results. RESULTS: Seventy patients were identified with average age of 67 (range 33 - 94). Overall hospital mortality was 72%. Patients were divided into three distinct groups, patients who recovered (27%), patients deceased despite surgical treatment (18%), and patients palliated on presentation (54%). Age was comparable between groups (61 vs. 69 vs. 69; p=.2). Length of stay was highest in the recovered group (41.6 vs. 12.3 vs. 2.8 d). Biochemically, only lactate level differed (3.1 vs. 2.3 vs. 5.3 mmol/L, p=.03). Both deceased and palliative group scored similarly but significantly higher than the recovered group in both the Charlson comorbidity index (CCI) (4.2 and 5.6 vs. 3.4, p=.02) and age-adjusted CCI (ACCI) (6.7 and 8.2 vs. 5; p<.01). Other co-morbidities of atrial fibrillation (AF) and hypertension were comparable. CONCLUSIONS: Raised ACCI confers poor outcomes in AMI despite surgical management. ACCI may be used to aid early decision making in AMI, predicting futility of treatment, and altering management goals to palliative comfort care.

Reversible Cerebral Vasoconstriction Syndrome in Patients with Coronavirus Disease: A Multicenter Case Series.

BACKGROUND AND OBJECTIVES: RCVS (Reversible Cerebral Vasoconstrictive Syndrome) is a condition associated with vasoactive agents that alter endothelial function. There is growing evidence that endothelial inflammation contributes to cerebrovascular disease in patients with coronavirus disease 2019 (COVID-19). In our study, we describe the clinical features, risk factors, and outcomes of RCVS in a multicenter case series of patients with COVID-19. MATERIALS AND METHODS: Multicenter retrospective case series. We collected clinical characteristics, imaging, and outcomes of patients with RCVS and COVID-19 identified at each participating site. RESULTS: Ten patients were identified, 7 women, ages 21 - 62 years. Risk factors included use of vasoconstrictive agents in 7 and history of migraine in 2. Presenting symptoms included thunderclap headache in 5 patients with recurrent headaches in 4. Eight were hypertensive on arrival to the hospital. Symptoms of COVID-19 included fever in 2, respiratory symptoms in 8, and gastrointestinal symptoms in 1. One patient did not have systemic COVID-19 symptoms. MRI showed subarachnoid hemorrhage in 3 cases, intraparenchymal hemorrhage in 2, acute ischemic stroke in 4, FLAIR hyperintensities in 2, and no abnormalities in 1 case. Neurovascular imaging showed focal segment irregularity and narrowing concerning for vasospasm of the left MCA in 4 cases and diffuse, multifocal narrowing of the intracranial vasculature in 6 cases. Outcomes varied, with 2 deaths, 2 remaining in the ICU, and 6 surviving to discharge with modified Rankin scale (mRS) scores of 0 (n=3), 2 (n=2), and 3 (n=1). CONCLUSIONS: Our series suggests that patients with COVID-19 may be at risk for RCVS, particularly in the setting of additional risk factors such as exposure to vasoactive agents. There was variability in the symptoms and severity of COVID-19, clinical characteristics, abnormalities on imaging, and mRS scores. However, a larger study is needed to validate a causal relationship between RCVS and COVID-19.

In vitro inhibitory activities of sugarcane extract on avian Eimeria sporozoites.

The current in vitro study aimed to investigate the effects of a processed sugarcane extract on the viability of avian Eimeria sporozoites. Treatments were applied to hatched sporozoites: 1) without additives (no-treatment control); 2) with ethanol; 3) with salinomycin; 4) with Polygain™. All treatments were incubated in RPMI media containing live sporozoites at 37 °C for 14 h and then the number of viable sporozoites were counted. Compared to the no-treatment control, Polygain™ decreased (P < 0.001) the counts of E. maxima, E. acervulina, E. bruneti, and E. mitis sporozoites to a level similar to salinomycin (P > 0.05). In conclusion, Polygain™ could be a potential candidate as an anticoccidial agent.

Cerebral Venous Sinus Thromboses in Patients with SARS-CoV-2 Infection: Three Cases and a Review of the Literature.

INTRODUCTION: Early studies suggest that acute cerebrovascular events may be common in patients with coronavirus disease 2019 (COVID-19) and may be associated with a high mortality rate. Most cerebrovascular events described have been ischemic strokes, but both intracerebral hemorrhage and rarely cerebral venous sinus thrombosis (CVST) have also been reported. The diagnosis of CVST can be elusive, with wide-ranging and nonspecific presenting symptoms that can include headache or altered sensorium alone. OBJECTIVE: To describe the presentation, barriers to diagnosis, treatment, and outcome of CVST in patients with COVID-19. METHODS: We abstracted data on all patients diagnosed with CVST and COVID-19 from March 1 to August 9, 2020 at Boston Medical Center. Subsequently, we reviewed the literature and extracted all published cases of CVST in patients with COVID-19 from January 1, 2020 through August 9, 2020 and included all studies with case descriptions. RESULTS: We describe the clinical features and management of CVST in 3 women with COVID-19 who developed CVST days to months after initial COVID-19 symptoms. Two patients presented with encephalopathy and without focal neurologic deficits, while one presented with visual symptoms. All patients were treated with intravenous hydration and anticoagulation. None suffered hemorrhagic complications, and all were discharged home. We identified 12 other patients with CVST in the setting of COVID-19 via literature search. There was a female predominance (54.5%), most patients presented with altered sensorium (54.5%), and there was a high mortality rate (36.4%). CONCLUSIONS: During this pandemic, clinicians should maintain a high index of suspicion for CVST in patients with a recent history of COVID-19 presenting with non-specific neurological symptoms such as headache to provide expedient management and prevent complications. The limited data suggests that CVST in COVID-19 is more prevalent in females and may be associated with high mortality.

Intravenous tPA for Acute Ischemic Stroke in Patients with COVID-19.

BACKGROUND/PURPOSE: Coronavirus disease 2019 (COVID-19) is associated with increased risk of acute ischemic stroke (AIS), however, there is a paucity of data regarding outcomes after administration of intravenous tissue plasminogen activator (IV tPA) for stroke in patients with COVID-19. METHODS: We present a multicenter case series from 9 centers in the United States of patients with acute neurological deficits consistent with AIS and COVID-19 who were treated with IV tPA. RESULTS: We identified 13 patients (mean age 62 (±9.8) years, 9 (69.2%) male). All received IV tPA and 3 cases also underwent mechanical thrombectomy. All patients had systemic symptoms consistent with COVID-19 at the time of admission: fever (5 patients), cough (7 patients), and dyspnea (8 patients). The median admission NIH stroke scale (NIHSS) score was 14.5 (range 3-26) and most patients (61.5%) improved at follow up (median NIHSS score 7.5, range 0-25). No systemic or symptomatic intracranial hemorrhages were seen. Stroke mechanisms included cardioembolic (3 patients), large artery atherosclerosis (2 patients), small vessel disease (1 patient), embolic stroke of undetermined source (3 patients), and cryptogenic with incomplete investigation (1 patient). Three patients were determined to have transient ischemic attacks or aborted strokes. Two out of 12 (16.6%) patients had elevated fibrinogen levels on admission (mean 262.2 ± 87.5 mg/dl), and 7 out of 11 (63.6%) patients had an elevated D-dimer level (mean 4284.6 ±3368.9 ng/ml). CONCLUSIONS: IV tPA may be safe and efficacious in COVID-19, but larger studies are needed to validate these results.

Effects of cLFchimera peptide on intestinal morphology, integrity, microbiota, and immune cells in broiler chickens challenged with necrotic enteritis.

Three hundred and sixty 1-day-old male broiler chicks were randomly allocated to 4 treatments of 6 replicates to evaluate the effects of cLFchimera, a recombinant antimicrobial peptide (AMP), on gut health attributes of broiler chickens under necrotic enteritis (NE) challenge. Treatments were as follows: (T1) unchallenged group fed with corn-soybean meal (CSM) without NE challenge and additives (NC); (T2) group fed with CSM and challenged with NE without any additives (PC); (T3) PC group supplemented with 20 mg cLFchimera/kg diet (AMP); (T4) PC group supplemented with 45 mg antibiotic (bacitracin methylene disalicylate)/kg diet (antibiotic). Birds were sampled for villi morphology, ileal microbiota, and jejunal gene expression of cytokines, tight junctions proteins, and mucin. Results showed that AMP ameliorated NE-related intestinal lesions, reduced mortality, and rehabilitated jejunal villi morphology in NE challenged birds. While the antibiotic non-selectively reduced the count of bacteria, AMP restored microflora balance in the ileum of challenged birds. cLFchimera regulated the expression of cytokines, junctional proteins, and mucin transcripts in the jejunum of NE challenged birds. In conclusion, cLFchimera can be a reliable candidate to substitute growth promoter antibiotics, while more research is required to unveil the exact mode of action of this synthetic peptide.

CT-Negative Subarachnoid Hemorrhage in the First Six Hours.

BACKGROUND: There are no reported cases of negative CT head in the first six hours after a thunderclap headache in a patient found to have an aneurysmal subarachnoid hemorrhage (SAH). METHODS: We present a case of an anemic patient who experienced aneurysmal SAH with a negative head CT within the first 6 h following thunderclap headache. RESULTS: A 47-year-old woman presented with a thunderclap headache and examination showed somnolence and marked meningismus. After a negative CT head was obtained within the first 6 hours of symptom onset, a non-traumatic lumbar puncture (LP) showed consistently bloody collection tubes, prompting repeat imaging that demonstrated a tiny amount of intraventricular hemorrhage. CT angiography revealed an intradural carotid artery aneurysm, and pipeline embolization was successfully performed. CONCLUSION: Non-contrast head CT may be falsely negative within the first 6 hours of aneurysmal SAH in the setting of anemia. In our case, the cause may not have been determined if an LP had not been performed. LP still has a role in diagnosing SAH, particularly in the setting of significant anemia, despite the high sensitivity of non-contrast head CT.