Stellate ganglion block: what else is necessary to include in the treatment of subarachnoid hemorrhage patients?

Cerebral vasospasm is determined as a temporary narrowing of cerebral arteries a few days after an aneurysmal subarachnoid hemorrhage. The onset of this vascular event usually evolves with new neurological deficits or progression of ischemic areas. The success of interventions to treat or revert this condition is not satisfying. In addition to cerebral vasospasm, early brain injury plays an important role as a contributor to subarachnoid hemorrhage's mortality. In this sense, stellate ganglion block appears as an alternative to reduce sympathetic system's activation, one of the main pathophysiological mechanisms involved in brain injury. Over the past few years, there is growing evidence that stellate ganglion block can contribute to decline patient morbidity from subarachnoid hemorrhage. Is it time to include this procedure as a standard treatment after aneurysm rupture?

Spillover of highly pathogenic avian influenza H5N1 virus to dairy cattle.

Highly pathogenic avian influenza (HPAI) H5N1 clade 2.3.4.4b virus has caused the death of millions of domestic birds and thousands of wild birds in the U.S. since January, 20221-4 Throughout this outbreak, spillovers to mammals have been frequently documented5-12. We report spillover of HPAI H5N1 virus in dairy cattle herds across several states in the U.S. The affected cows displayed clinical signs encompassing decreased feed intake, altered fecal consistency, respiratory distress, and decreased milk production with abnormal milk. Infectious virus and viral RNA were consistently detected in milk from affected cows. Viral distribution in tissues via immunohistochemistry and in situ hybridization revealed a distinct tropism of the virus for the epithelial cells lining the alveoli of the mammary gland in cows. Whole viral genome sequences recovered from dairy cows, birds, domestic cats, and a raccoon from affected farms indicated multidirectional interspecies transmissions. Epidemiologic and genomic data revealed efficient cow-to-cow transmission after apparently healthy cows from an affected farm were transported to a premise in a different state. These results demonstrate the transmission of HPAI H5N1 clade 2.3.4.4b virus at a non-traditional interface underscoring the ability of the virus to cross species barriers.

Distinct Mechanisms of Type 3 Secretion System Recognition Control LTB4 Synthesis in Neutrophils versus Macrophages.

Leukotriene B4 (LTB4) is critical for initiating the inflammatory cascade in response to infection. However, Yersinia pestis colonizes the host by inhibiting the timely synthesis of LTB4 and inflammation. Here, we show that the bacterial type 3 secretion system (T3SS) is the primary pathogen associated molecular pattern (PAMP) responsible for LTB4 production by leukocytes in response to Yersinia and Salmonella, but synthesis is inhibited by the Yop effectors during Yersinia interactions. Moreover, we unexpectedly discovered that T3SS-mediated LTB4 synthesis by neutrophils and macrophages require two distinct host signaling pathways. We show that the SKAP2/PLC signaling pathway is essential for LTB4 production by neutrophils but not macrophages. Instead, phagocytosis and the NLRP3/CASP1 inflammasome are needed for LTB4 synthesis by macrophages. Finally, while recognition of the T3SS is required for LTB4 production, we also discovered a second unrelated PAMP-mediated signal independently activates the MAP kinase pathway needed for LTB4 synthesis. Together, these data demonstrate significant differences in the signaling pathways required by macrophages and neutrophils to quickly respond to bacterial infections.

STA-MCA Double-Barrel Bypass: A Systematic Review of Technique and Single-Arm Meta-Analysis of Outcomes.

INTRODUCTION: Conventionally, one branch of the superficial temporal artery (STA) is utilized to revascularize the middle cerebral artery (MCA). However, there is the possibility of utilizing both branches of the STA when performing the bypass, characterizing the double-barrel (DB) STA-MCA bypass. Notably, a lack of studies evaluating this technique led the authors to conduct a systematic review and single-arm meta-analysis. METHODS: PubMed, Embase and Web of Science were searched systematically for publications of DB-STA-MCA bypass on November 1st, 2023. The findings were reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Case reports were not included for statistical analysis purposes. RESULTS: The review included 408 patients and 534 bypasses from 34 studies. The main etiology was Moyamoya disease (64.6%), followed by cerebral ischemia (22.2%) and aneurysms (12.5%). The median of the mean follow-ups of each study was 12.8 months (range 1.5-87.9). The postoperative patency was 100%. The follow-up patency was 98% (95% CI: 96%-100%; I2 = 0%). The procedure-related mortality was 0% (95% CI: 0%-1%; I2 = 0%). Aneurysms obtained 87% (95% CI: 72%-100%; I2 = 4%) of good clinical outcomes, while Moyamoya disease yielded a rate of 70% (95% CI: 10%-100%; I2 = 97%). Ischemic complications occurred at a rate of 6% (95% CI: 2%-11%; I2 = 36%), while hemorrhagic occurred at 6% (95% CI: 1%-11%; I2 = 56%). Hyperperfusion syndrome rate was calculated as 18% (7%-30%; I2 = 55%) for Moyamoya disease. CONCLUSIONS: The procedure appears to be safe, with excellent patency rates. The clinical efficacy for ischemic and Moyamoya diseases warrants further standardized robust investigation with a broader number of patients, and aneurysm studies are required to enhance sample sizes. The main complication for the Moyamoya subgroup is hyperperfusion syndrome.

Are ventriculopleural shunts the second option for treating hydrocephalus? A meta-analysis of 543 patients.

BACKGROUND: Some centers utilize ventriculopleural shunt (VPLS) for treating hydrocephalus when conventional approaches are not feasible. Nonetheless, the literature regarding this approach is scarce. PURPOSE: Evaluate the outcomes of VPLS through a single-arm meta-analysis. METHODS: Following PRISMA guidelines, the authors systematically searched for articles utilizing the VPLS in a cohort with more than four patients. Outcomes included: mortality, pleural effusion, number of patients who underwent revisions, obstructions, shunt migration, emphysema, and subdural hematoma. RESULTS: A total of 404 articles were reviewed, resulting in the inclusion of 13 retrospective studies encompassing 543 patients, with the majority being children (62.6 %). The median average follow-up period was 35.4 months (10-64.1). After analysis, results yielded a revision rate of 54 % (95 % CI: 44 %-64 %; I2=73 %). The most common complication observed was pleural effusion, with a post-analysis incidence of 16 % (95 % CI: 11 %-21 %; I2=63 %), followed by infections at 7 % (95 % CI: 4 %-10 %; I2=33 %). Shunt obstruction occurred in 13 % (95 % CI: 4 %-21 %; I2=84 %) of cases after analysis, while migrations, overdrainage, subdural hematoma, and cutaneous emphysema had minimal occurrence rates (0 %, 95 % CI: 0 %-1 %; I2=0 %). Notably, there were no reported cases of shunt-related mortality. CONCLUSION: VPLS can be considered when there are no other suitable options for placing the distal catheter. However, the notable rates of shunt revisions, pleural effusion, infections, and the inherent heterogeneity of outcomes currently limit the widespread adoption of VPLS. In this scenario, other alternatives should be given priority.

Emergence of transmissible SARS-CoV-2 variants with decreased sensitivity to antivirals in immunocompromised patients with persistent infections.

We investigated the impact of antiviral treatment on the emergence of SARS-CoV-2 resistance during persistent infections in immunocompromised patients (n=15). All patients received remdesivir and some also received nirmatrelvir-ritonavir or monoclonal antibodies. Sequence analysis showed that nine patients carried viruses with mutations in the nsp12 (RNA dependent RNA polymerase), while four had viruses with nsp5 (3C protease) mutations. Infectious SARS-CoV-2 with a double mutation in nsp5 (T169I) and nsp12 (V792I) was recovered from respiratory secretions 77 days after initial COVID-19 diagnosis from a patient treated with remdesivir and nirmatrelvir-ritonavir. In vitro characterization confirmed its decreased sensitivity to remdesivir and nirmatrelvir, which was overcome by combined antiviral treatment. Studies in golden Syrian hamsters demonstrated efficient transmission to contact animals. This study documents the isolation of SARS-CoV-2 carrying resistance mutations to both nirmatrelvir and remdesivir from a patient and demonstrates its transmissibility in vivo.

The impact of revascularization strategy on clinical failure, hemodynamic failure, and chronic limb-threatening ischemia symptoms in the BEST-CLI Trial.

OBJECTIVE: Sustained clinical and hemodynamic benefit after revascularization for chronic limb-threatening ischemia (CLTI) is needed to resolve symptoms and prevent limb loss. We sought to compare rates of clinical and hemodynamic failure as well as resolution of initial and prevention of recurrent CLTI after endovascular (ENDO) vs bypass (OPEN) revascularization in the Best-Endovascular-versus-best-Surgical-Therapy-in-patients-with-CLTI (BEST-CLI) trial. METHODS: As planned secondary analyses of the BEST-CLI trial, we examined the rates of (1) clinical failure (a composite of all-cause death, above-ankle amputation, major reintervention, and degradation of WIfI stage); (2) hemodynamic failure (a composite of above-ankle amputation, major and minor reintervention to maintain index limb patency, failure to an initial increase or a subsequent decrease in ankle brachial index of 0.15 or toe brachial index of 0.10, and radiographic evidence of treatment stenosis or occlusion); (3) time to resolution of presenting CLTI symptoms; and (4) incidence of recurrent CLTI. Time-to-event analyses were performed by intention-to-treat assignment in both trial cohorts (cohort 1: suitable single segment great saphenous vein [SSGSV], N = 1434; cohort 2: lacking suitable SSGSV, N = 396), and multivariate stratified Cox regression models were created. RESULTS: In cohort 1, there was a significant difference in time to clinical failure (log-rank P < .001), hemodynamic failure (log-rank P < .001), and resolution of presenting symptoms (log-rank P = .009) in favor of OPEN. In cohort 2, there was a significantly lower rate of hemodynamic failure (log-rank P = .006) favoring OPEN, and no significant difference in time to clinical failure or resolution of presenting symptoms. Multivariate analysis revealed that assignment to OPEN was associated with a significantly lower risk of clinical and hemodynamic failure in both cohorts and a significantly higher likelihood of resolving initial and preventing recurrent CLTI symptoms in cohort 1, including after adjustment for key baseline patient covariates (end-stage renal disease [ESRD], prior revascularization, smoking, diabetes, age >80 years, WIfI stage, tissue loss, and infrapopliteal disease). Factors independently associated with clinical failure included age >80 years in cohort 1 and ESRD across both cohorts. ESRD was associated with hemodynamic failure in cohort 1. Factors associated with slower resolution of presenting symptoms included diabetes in cohort 1 and WIfI stage in cohort 2. CONCLUSIONS: Durable clinical and hemodynamic benefit after revascularization for CLTI is important to avoid persistent and recurrent CLTI, reinterventions, and limb loss. When compared with ENDO, initial treatment with OPEN surgical bypass, particularly with available saphenous vein, is associated with improved clinical and hemodynamic outcomes and enhanced resolution of CLTI symptoms.

Clinical and Technical Outcomes of Intracranial-Intracranial Bypass for Treating Complex Intracranial Aneurysms: An Analysis of 255 Patients.

BACKGROUND: Despite the recent increase in publications centered on intracranial-intracranial (IC-IC) bypasses for complex aneurysms, there is no systematic evidence regarding their outcomes. The purpose was to assess the outcomes of patients subjected to IC-IC bypass for aneurysms. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis, a systematic review was conducted. Criteria for inclusion entailed studies with a cohort of at least 4 patients having undergone IC-IC bypass for aneurysms, detailing at least one outcome, such as patency, clinical outcomes, complications, and procedure-related mortality. When the study included patients who had undergone extracranial-intracranial (EC-IC) bypass, the authors extracted the patency and clinical data to juxtapose them with the results of IC-IC. RESULTS: Of the 2509 shortlisted studies, 22 met our inclusion criteria, encompassing 255 patients and 263 IC-IC bypass procedures. The IC-IC bypass procedure exhibited a patency rate of 93% (95% confidence interval [CI]: 89%-95%). The patency rate of IC-IC and EC-IC bypasses did not significantly differ (odds ratio=0.60 [95% CI: 0.18-1.96]). Concerning clinical outcomes, 91% of the IC-IC patients had positive results (95% CI: 85%-97%), with no significant disparity between the IC-IC and EC-IC groups (odds ratio=1.29 [95% CI: 0.43-3.88]). After analysis, the complication rate was 11% (95% CI: 5%-18%). Procedure-related mortality was 1% (95% CI: 0%-4%). CONCLUSIONS: IC-IC bypass is valuable for the treatment of complex intracranial aneurysms, boasting high patency and positive clinical outcomes. Complications are unusual, and procedure-related mortality is minimal. Comparing IC-IC and EC-IC led to no significant differences.

Identification of an Immunodominant B-Cell Epitope in African Swine Fever Virus p30 Protein and Evidence of p30 Antibody-Mediated Antibody Dependent Cellular Cytotoxicity.

African Swine Fever Virus (ASFV) is a large dsDNA virus that encodes at least 150 proteins. The complexity of ASFV and lack of knowledge of effector immune functions and protective antigens have hindered the development of safe and effective ASF vaccines. In this study, we constructed four Orf virus recombinant vectors expressing individual ASFV genes B602L, -CP204L, E184L, and -I73R (ORFVΔ121-ASFV-B602L, -CP204L, -E184L, and -I73R). All recombinant viruses expressed the heterologous ASFV proteins in vitro. We then evaluated the immunogenicity of the recombinants by immunizing four-week-old piglets. In two independent animal studies, we observed high antibody titers against ASFV p30, encoded by CP204L gene. Using Pepscan ELISA, we identified a linear B-cell epitope of 12 amino acids in length (Peptide 15) located in an exposed loop region of p30 as an immunodominant ASFV epitope. Additionally, antibodies elicited against ASFV p30 presented antibody-dependent cellular cytotoxicity (ADCC) activity. These results underscore the role of p30 on antibody responses elicited against ASFV and highlight an important functional epitope that contributes to p30-specific antibody responses.

Fractal structures in the chaotic advection of passive scalars in leaky planar hydrodynamical flows.

The advection of passive scalars in time-independent two-dimensional incompressible fluid flows is an integrable Hamiltonian system. It becomes non-integrable if the corresponding stream function depends explicitly on time, allowing the possibility of chaotic advection of particles. We consider for a specific model (double gyre flow), a given number of exits through which advected particles can leak, without disturbing the flow itself. We investigate fractal escape basins in this problem and characterize fractality by computing the uncertainty exponent and basin entropy. Furthermore, we observe the presence of basin boundaries with points exhibiting the Wada property, i.e., boundary points that separate three or more escape basins.

Posterior Inferior Cerebellar Artery-Posterior Inferior Cerebellar Artery Bypass versus Occipital Artery-Posterior Inferior Cerebellar Artery Bypass for Treating Posterior Circulation Aneurysms: A Systematic Review and Comparative Meta-Analysis.

BACKGROUND: When traditional therapies are unsuitable, revascularization becomes essential for managing posterior inferior cerebellar artery (PICA) or vertebral artery aneurysms. Notably, the PICA-PICA bypass has emerged as a promising option, overshadowing the occipital artery-PICA (OA-PICA) bypass. The objective was to compare the safety and efficacy of OA-PICA and PICA-PICA bypasses. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, we conducted a systematic review and meta-analysis to evaluate the safety and efficacy of OA-PICA and PICA-PICA bypasses for treating posterior circulation aneurysms. RESULTS: We analyzed 13 studies for the PICA-PICA bypass and 16 studies on the OA-PICA bypass, involving 84 and 110 patients, respectively. The median average follow-up for PICA-PICA bypass was 8 months (2-50.3 months), while for OA-PICA, it was 27.8 months (6-84 months). The patency rate for OA-PICA was 97% (95% confidence interval [CI]: 92%-100%) and 100% (95% CI: 95%-100%) for PICA-PICA. Complication rates were 29% (95% CI: 10%-47%) for OA-PICA and 12% (95% CI: 3%-21%) for PICA-PICA. Good clinical outcomes were observed in 71% (95% CI: 52%-90%) of OA-PICA patients and 87% (95% CI: 75%-100%) of PICA-PICA patients. Procedure-related mortality was 1% (95% CI: 0%-6%) for OA-PICA and 1% (95% CI: 0%-10%) for PICA-PICA. CONCLUSIONS: Both procedures have demonstrated promising results in efficacy and safety. PICA-PICA exhibits slightly better patency rates, better clinical outcomes, and fewer complications, but with a lack of substantial follow-up and a smaller sample size. The choice between these procedures should be based on the surgeon's expertise and the patient's anatomy.

Acute effects of ipsilateral semitendinosus and gracilis autograft anterior cruciate ligament reconstruction on lower limb muscle activation

There is little information regarding the acute repercussions of anterior cruciate ligament (ACL) reconstruction on muscle activation, especially on the proximal hip muscles. Thus, this study analyzed the acute effects of ACL reconstruction with doubled semitendinosus/gracilis (ST/G) autografts on lower limb muscle activation. Fourteen male recreational athletes that presented a primary unilateral ACL rupture and underwent the ACL reconstruction with an ST/G graft. Surface electromyographic (sEMG) signal were recorded from each participant during the maximal voluntary isometric contraction (MVIC) of the gluteus maximus and gluteus medius, vastus lateralis and vastus medialis, semitendinosus, biceps femoris, and medial gastrocnemius muscles and also during bipodal mini-squatting with open and closed eyes, before surgery and 15 days postoperatively. (sEMG) signal were normalized to isometric peak electromyography. The postoperative assessment showed reduced muscle activation in the gluteus maximus (p = 0.013, d:0.48) in non-operated limb and also in the muscle gluteus medius (p = 0.013, d:0.79), vastus medialis (p = 0.035, d:0.63) semitendinosus (p = 0.001, d:2.46), biceps femoris (p<0.001, d:1.5), and medial gastrocnemius (p = 0.001, d:1.45) during MVIC in the operated limb. The postoperative assessment also revealed alterations in the sEMG activity of the hip and local thigh muscles in the operated and non-operated limbs during mini-squatting with opened eyes and closed eyes (p<0.05). ACL reconstruction surgery with a doubled ST/G autograft may promote immediate changes in lower limb muscle activation of the operated and non-operated limb. (AU)

Tuning Molecular Motion Enhances Intrinsic Fluorescence in Peptide Amphiphile Nanofibers.

Peptide amphiphiles (PAs) are highly tunable molecules that were recently found to exhibit aggregation-induced emission (AIE) when they self-assemble into nanofibers. Here, we leverage decades of molecular design and self-assembly study of PAs to strategically tune their molecular motion within nanofibers to enhance AIE, making them a highly useful platform for applications such as sensing, bioimaging, or materials property characterization. Since AIE increases when aggregated molecules are rigidly and closely packed, we altered the four most closely packed amino acids nearest to the hydrophobic core by varying the order and composition of glycine, alanine, and valine pairs. Of the six PA designs studied, C16VVAAK2 had the highest quantum yield at 0.17, which is a more than 10-fold increase from other PA designs including the very similar C16AAVVK2, highlighting the importance of precise amino acid placement to anchor rigidity closest to the core. We also altered temperature to increase AIE. C16VVAAK2 exhibited an additional 4-fold increase in maximum fluorescence intensity when the temperature was raised from 5 to 65 °C. As the temperature increased, the secondary structure transitioned from ß-sheet to random coil, indicating that further packing an already aligned molecular system makes it even more readily able to transfer energy between the electron-rich amides. This work both unveils a highly fluorescent AIE PA system design and sheds insights into the molecular orientation and packing design traits that can significantly enhance AIE in self-assembling systems.

Surface-enhanced Raman Spectroscopy in urinalysis of hypertension patients with kidney disease.

Arterial hypertension (AH) is a multifactorial and asymptomatic disease that affects vital organs such as the kidneys and heart. Considering its prevalence and the associated severe health repercussions, hypertension has become a disease of great relevance for public health across the globe. Conventionally, the classification of an individual as hypertensive or non-hypertensive is conducted through ambulatory blood pressure monitoring over a 24-h period. Although this method provides a reliable diagnosis, it has notable limitations, such as additional costs, intolerance experienced by some patients, and interferences derived from physical activities. Moreover, some patients with significant renal impairment may not present proteinuria. Accordingly, alternative methodologies are applied for the classification of individuals as hypertensive or non-hypertensive, such as the detection of metabolites in urine samples through liquid chromatography or mass spectrometry. However, the high cost of these techniques limits their applicability for clinical use. Consequently, an alternative methodology was developed for the detection of molecular patterns in urine collected from hypertension patients. This study generated a direct discrimination model for hypertensive and non-hypertensive individuals through the amplification of Raman signals in urine samples based on gold nanoparticles and supported by chemometric techniques such as partial least squares-discriminant analysis (PLS-DA). Specifically, 162 patient urine samples were used to create a PLS-DA model. These samples included 87 urine samples from patients diagnosed with hypertension and 75 samples from non-hypertensive volunteers. In the AH group, 35 patients were diagnosed with kidney damage and were further classified into a subgroup termed (RAH). The PLS-DA model with 4 latent variables (LV) was used to classify the hypertensive patients with external validation prediction (P) sensitivity of 86.4%, P specificity of 77.8%, and P accuracy of 82.5%. This study demonstrates the ability of surface-enhanced Raman spectroscopy to differentiate between hypertensive and non-hypertensive patients through urine samples, representing a significant advance in the detection and management of AH. Additionally, the same model was then used to discriminate only patients diagnosed with renal damage and controls with a P sensitivity of 100%, P specificity of 77.8%, and P accuracy of 82.5%.