Grape Pomace Polyphenols Reduce Acute Inflammatory Response Induced by Carrageenan in a Murine Model.

Grape pomace (GP), a by-product of wine production, contains bioactive polyphenols with potential health benefits. This study investigates the anti-inflammatory properties of a polyphenolic fraction derived from GP, obtained by ultrasound-microwave hybrid extraction and purified using ion-exchange chromatography. In the inflammation model, mice were divided into six groups: intact, carrageenan, indomethacin, and three GP polyphenols treatment groups. Paw edema was induced by subplantar injection of carrageenan, and the GP polyphenols were administered intraperitoneally at doses of 10, 20, and 40 mg/kg. The anti-inflammatory effect was evaluated by measuring paw volume, and expression of inflammatory markers: cyclooxygenase-2 (COX-2), myeloperoxidase (MPO), and cytokines (IL-1ß and IL-6), along with lipid peroxidation levels. The GP polyphenols significantly reduced paw edema and expression levels of COX-2, MPO, and cytokines in a dose-dependent manner effect, with the highest dose showing the greatest reduction. Additionally, lipid peroxidation levels were also decreased by GP polyphenols treatment at doses of 10 and 20 mg/kg. These findings suggest that ultrasound-microwave extraction combined with amberlite purification proved to be effective in obtaining a polyphenolic-rich fraction from GP. Thus, GP polyphenols may serve as a natural anti-inflammatory and antioxidant agent for treating inflammation and oxidative stress-related diseases.

Dental anxiety and oral health-related quality of life before and after non-surgical periodontal treatment.

OBJECTIVES: To (1) investigate dental anxiety (DA) and oral health-related quality of life (OHRQOL) before and after non-surgical periodontal treatment (NSPT) and (2) determine correlations between these patient-reported measures. MATERIALS AND METHODS: Demographics, smoking habits, dental pain, Modified Corah's Dental Anxiety Scale (MDAS), and Oral Health Impact Profile (OHIP-14) were assessed in eighty-two participants. RESULTS: Mean age was 48.3 years ± 11.5. At baseline, 8.5% reported being active smokers. Of non-smokers, 11% reported being an ex-smoker. After NSPT, 11.0% reported smoking. Patients' maximal pain in the last month decreased after therapy. Before treatment, participants reported higher DA. Extreme DA was observed in 8.5% of participants before therapy. Afterwards, 2.4% of participants reported extreme DA. Fear of having a foreign object in the mouth decreased after NSPT. All OHIP-14 scores, except functional limitation, improved post-treatment. Higher DA was associated with worse OHRQoL before treatment. After treatment, total MDAS score was associated with OHIP-14 global score, physical pain, psychological disability, and social disability. Worse MDAS sub-scores were associated with a higher OHIP-14 global score. Individuals with "normal/slight anxiety" had a significant improvement in OHRQoL, whereas people in the "moderate and extreme anxiety" group did not report a significant improvement. Patients diagnosed with generalized periodontitis (GP) stage III grade B and GP stage IV grade B reported less anxiety after NSPT. CONCLUSIONS: Associations of MDAS subcategories with OHIP-14 domain scores were found before and after therapy. DA decreases and OHRQoL enhances after NSPT in patients with "normal/slight" anxiety to dental treatment. Dental practitioners should plan strategies to cope with anxiety to dental treatment and prevent decreases in OHRQoL. CLINICAL RELEVANCE: Within the limitations of this study, DA and OHRQoL were positively correlated in patients with periodontitis, before and after NSPT, using the MDAS and OHIP-14 questionnaires. The results of our study suggest that treatment is effective in terms of alleviating DA and improving oral health, along with quality of life, in patients that report "normal/slight" anxiety to dental treatment. Nonetheless, results must be interpreted with caution since patients are generally anxious before any type of dental treatment. DA may not just be confined to NSPT per se. According to our results, evaluation of both outcomes should be an integral part of routine periodontal clinical evaluation and periodontal reevaluation of initial therapy. It is important that clinicians learn to identify patients that suffer from anxiety and take time to explain the treatment procedures to the patient, to strive for patient's emotional well-being before, during, and after dental care services. The use of specific questionnaires for both DA and OHRQoL may be more appropriate to demonstrate the psychological and quality of life differences due to periodontal disease and NSPT.

Chimeric SCIP flap with iliac bone for reconstruction of foot first ray in a radiated surgical bed: A case report.

Surgical management of sarcoma has evolved from amputation to limb salvage. Nevertheless, subsequent resections in previously irradiated feet are still challenging to reconstruct. First foot ray functional reconstruction is relevant due to its function in weight-bearing and gait. The reconstruction should include a thin, pliable and non-shearing skin paddle with vascularized long cortical bone to mimic the first metatarsal. A clinical case of a 37-year-old patient with a second sarcoma recurrence of the first metatarsal is presented. The patient was irradiated before this new recurrence and had a previous reconstruction with fibula allograft, but subsequently developed a first metatarsal pseudoarthrosis. A wide resection was performed (3.5 cm bone defect) and immediate soft tissue and bone reconstruction with a chimeric SCIP flap with a 17 × 8 cm skin paddle and 3.5 × 1.5 cm iliac bone (cSCIP-IB). At 7 months post-operatively, the patient was able to resumed full weight-bearing. Three years later, remains without disease progression. CSCIP-IB is a good option for foot first ray reconstruction in irradiated beds. This flap has low donor site morbidity and a higher ossification success rate compared to bone allografts.

Therapeutic targeting of HER2-CB2R heteromers in HER2-positive breast cancer.

Although human epidermal growth factor receptor 2 (HER2)-targeted therapies have dramatically improved the clinical outcome of HER2-positive breast cancer patients, innate and acquired resistance remains an important clinical challenge. New therapeutic approaches and diagnostic tools for identification, stratification, and treatment of patients at higher risk of resistance and recurrence are therefore warranted. Here, we unveil a mechanism controlling the oncogenic activity of HER2: heteromerization with the cannabinoid receptor CB2R. We show that HER2 physically interacts with CB2R in breast cancer cells, and that the expression of these heteromers correlates with poor patient prognosis. The cannabinoid Δ9-tetrahydrocannabinol (THC) disrupts HER2-CB2R complexes by selectively binding to CB2R, which leads to (i) the inactivation of HER2 through disruption of HER2-HER2 homodimers, and (ii) the subsequent degradation of HER2 by the proteasome via the E3 ligase c-CBL. This in turn triggers antitumor responses in vitro and in vivo. Selective targeting of CB2R transmembrane region 5 mimicked THC effects. Together, these findings define HER2-CB2R heteromers as new potential targets for antitumor therapies and biomarkers with prognostic value in HER2-positive breast cancer.

Intravenous Thrombolysis Guided by Perfusion CT with Alteplase in >4.5 Hours from Stroke Onset.

INTRODUCTION: The benefit of intravenous thrombolysis (IVT) in wake-up stroke (WUS), stroke of unknown time of onset (SUKO), or when time exceeds 4.5 h from last-seen-normal (LSN) guided by CT perfusion (CTP) or MRI has been recently suggested. However, there is limited information of IVT in those patients in real-world studies. OBJECTIVE: Our aim was to evaluate safety and efficacy of IVT selected by CTP in patients with WUS, SUKO, or stroke of time onset beyond 4.5 h. MATERIAL AND METHODS: We studied a prospective cohort of patients who underwent IVT from January 2010 to December 2017. Two groups were defined: standard of care group (SC) included patients with time onset <4.5 h and CTP group included patients with WUS, SUKO, or onset beyond >4.5 h from LSN with penumbra area in CTP. We evaluated baseline characteristics, functional outcomes according to modified Rankin Scale (mRS) at discharge and at 90 days, and intracranial hemorrhages rates. RESULTS: 657 patients were studied: 604 (92%) were treated in the SC group and 53 (8%) in the CTP group. The mean NIHSS score was 9.8 in the CTP group versus 13 in the SC group (p = 0.001). Seventeen patients in the CTP group (32.1%) received bridging therapy with mechanical thrombectomy (MT). Last time seen well-to-needle time was 538 versus 155 min (p < 0.001). The incidence of symptomatic intracranial hemorrhage was equal in both groups (3.8 vs. 3.8%, p = 1). Good functional outcome (mRS < 2) was achieved in both groups (72 vs. 60.4%, p = 0.107). CONCLUSIONS: IVT in patients with WUS, SUKO, or stroke beyond >4.5 h from LSN, with salvageable brain tissue on CTP, seems to be safe and has similar functional outcomes at 90 days to the standard therapeutic window, even when combined with MT.

A Latin American survey on demographic aspects of hospitalized, decompensated cirrhotic patients and the resources for their management.

INTRODUCTION & OBJECTIVES: Liver cirrhosis is a major cause of mortality worldwide. Adequate diagnosis and treatment of decompensating events requires of both medical skills and updated technical resources. The objectives of this study were to search the demographic profile of hospitalized cirrhotic patients in a group of Latin American hospitals and the availability of expertise/facilities for the diagnosis and therapy of decompensation episodes. METHODS: A cross sectional, multicenter survey of hospitalized cirrhotic patients. RESULTS: 377 patients, (62% males; 58±11 years) (BMI>25, 57%; diabetes 32%) were hospitalized at 65 centers (63 urbans; 57 academically affiliated) in 13 countries on the survey date. Main admission causes were ascites, gastrointestinal bleeding, hepatic encephalopathy and spontaneous bacterial peritonitis/other infections. Most prevalent etiologies were alcohol-related (AR) (40%); non-alcoholic-steatohepatitis (NASH) (23%), hepatitis C virus infection (HCV) (7%) and autoimmune hepatitis (AIH) (6%). The most frequent concurrent etiologies were AR+NASH. Expertise and resources in every analyzed issue were highly available among participating centers, mostly accomplishing valid guidelines. However, availability of these facilities was significantly higher at institutions located in areas with population>500,000 (n=45) and in those having a higher complexity level (Gastrointestinal, Liver and Internal Medicine Departments at the same hospital (n=22). CONCLUSIONS: The epidemiological etiologic profile in hospitalized, decompensated cirrhotic patients in Latin America is similar to main contemporary emergent agents worldwide. Medical and technical resources are highly available, mostly at great population urban areas and high complexity medical centers. Main diagnostic and therapeutic approaches accomplish current guidelines recommendations.

Predictive Value of Serum Antibodies and Point Mutations of AQP4, AQP1 and MOG in A Cohort of Spanish Patients with Neuromyelitis Optica Spectrum Disorders.

The detection of IgG aquaporin-4 antibodies in the serum of patients with Neuromyelitis optica (NMO) has dramatically improved the diagnosis of this disease and its distinction from multiple sclerosis. Recently, a group of patients have been described who have an NMO spectrum disorder (NMOsd) and who are seronegative for AQP4 antibodies but positive for IgG aquaporin-1 (AQP1) or myelin oligodendrocyte glycoprotein (MOG) antibodies. The purpose of this study was to determine whether AQP1 and MOG could be considered new biomarkers of this disease; and if point mutations in the gDNA of AQP4, AQP1 and MOG genes could be associated with the etiology of NMOsd. We evaluated the diagnostic capability of ELISA and cell-based assays (CBA), and analyzed their reliability, specificity, and sensitivity in detecting antibodies against these three proteins. The results showed that both assays can recognize these antigen proteins under appropriate conditions, but only anti-AQP4 antibodies, and not AQP1 or MOG, appears to be a clear biomarker for NMOsd. CBA is the best method for detecting these antibodies; and serum levels of AQP4 antibodies do not correlate with the progression of this disease. So far, the sequencing analysis has not revealed a genetic basis for the etiology of NMOsd, but a more extensive analysis is required before definitive conclusions can be drawn.

[Nosocomial pneumonia in patients with haematological malignancies]. / Neumonía nosocomial (NN) en pacientes con neoplasias hematológicas (NH).

INTRODUCTION: Nosocomial pneumonia (NP) in patients with hematological malignancies (HM) has an attributable mortality over 90%. There are few studies that report the incidence of nosocomial infections in patients with HM. OBJECTIVE: To describe the epidemiology and clinical course of NP in a cohort of patients with hematologic malignancies. MATERIAL AND METHODS: Single-center study of patients with leukemia, lymphoma or multiple myeloma diagnosed with NP, hospitalized between January 2011 and December 2012. RESULTS: One-hundred and five NP were recorded: 51 leukemias (48%) and 45 lymphomas (43%); 50 (48%) were in relapse or progression. Median days for NP development were 13 days (IQ 6-20). Sixty percent of the patients had severe neutropenia. The most frequent symptom was fever 73 (70%). CT scan showed infiltrates in 100% of cases; 45 (43%) with findings suggestive of invasive fungal infection. Seven (7%) had confirmed invasive fungal infection, possible 9 (9%) and 45 (43%) probable. There were 99 cultures taken, 30 blood cultures (67% were positive) and 31 sputum (71% positive). Sixty percent of Gramnegative bacteria were multi-drug resistant and 50% of the Grampositive, E. coli, 19 (30%) was the most frequent isolated, Aspergillus spp. was the third, but the one with the highest associated mortality. Attributable mortality for pneumonia was 50% and 73% in patients that required mechanical ventilation (p = 0.001). CONCLUSIONS: We observed a high mortality rate in patients with HM and NP. Standardized diagnostic routes are needed for patients with HM with suspicion of pneumonia. Novel diagnostic techniques to enhance Aspergillus and respiratory viruses diagnosis should be introduced in this setting.

[Postoperative bed header position after burr-hole drainage of chronic subdural haematoma: systematic review and meta-analysis of randomised controlled trials]. / Posicionamiento postoperatorio de la cabecera tras drenaje de hematomas subdurales crónicos por trepanación: Revisión sistemática y metaanálisis de estudios controlados aleatorizados.

INTRODUCTION: Several studies have suggested the possible influence of postoperative bed header position on the risk of symptomatic recurrences and medical complications in patients who have been intervened due chronic subdural haematomas. Nevertheless, this hypothesis has not been assessed by a meta-analysis. METHODS: All randomised controlled trials analysing symptomatic recurrence rates in patients who underwent burr-hole drainage of chronic subdural haematomas, describing postoperative bed header positioning, were included. The primary outcome was risk of recurrence and the secondary outcome were the risks of reoperation and medical complications. Results were presented as pooled relative risks, with 95% confidence intervals. RESULTS: A total of 4 controlled studies were included. Pooled relative risks were: symptomatic recurrences 0.51 ([95% CI: 0.22-1.16]; P=.11), reoperations, 1.07 ([95% CI: 0.42-2.69]; P=.89) and medical complications, 1.15 ([95% CI: 0.7-1.91]; P=.58). No statistically significant heterogeneity was found in any of the analyses. CONCLUSION: There were no differences regarding frequency of symptomatic recurrences, reoperations or medical complications in patients who were maintained in a flat position compared with those whose bed header was elevated during the postoperative course. Despite there being consistency between the results, there is a potential risk of bias; thus proscribing definitive recommendations until studies with higher methodological quality are available.

Management of Massive Flank Hernia After Lateral Lumbar Fusion: Preoperative Botulinum Toxin Injections and Open Repair - A Case Report.

BACKGROUND Incisional flank hernias represent a complication after lateral lumbar spine surgery. Given the increasing rate of lateral lumbar interbody fusions, the rate of incisional flank hernias will increase. Since there are no reports of open massive flank hernia repair utilizing preoperative botulinum injections, we sought to publish this technique to provide surgeons with an innovative method for preoperatively treating patients with massive flank hernias. CASE REPORT A 75-year-old man with a history of coronary artery disease, chronic kidney disease, and abdominal hernia repair presented for evaluation of left lateral abdominal and left lower back bulging for 5 months. The symptoms began after an L2-L4 lateral lumbar spinal fusion. Physical examination revealed a left posterior lateral flank bulge. Computed tomography (CT) showed a fat-containing left posterolateral abdominal hernia. The patient was scheduled for CT-guided lateral abdominal wall botulinum injections, followed by open flank hernia repair. He tolerated the surgery well, was admitted for pain control, and discharged on day 2. Repeat imaging with CT at 3 months showed no evidence of patient's prior hernia defect. CONCLUSIONS Open flank hernia repair, in conjunction with preoperative botulinum toxin injections, allows for optimal visualization and re-approximation of the myofascial components of flank hernia defects. Failure to achieve adequate myofascial and skin closure, along with mesh reinforcement, in open flank hernia repair can result in various surgical site complications, including incisional flank hernia recurrence. We recommend further investigation on the benefits of botulinum injections as an adjunct in management of massive flank hernias.

Posttraumatic Scrotal Reconstruction with a Pedicled "Extended" Superficial Circumflex Iliac Artery Perforator Flap: A Case Report.

The superficial circumflex iliac artery (SCIA) perforator (SCIP) flap has been used for scrotal reconstruction after Fournier's gangrene, skin cancer, or infections. However, there are few publications with regard to penoscrotal reconstruction after a traumatic injury with this flap. In this article, we propose a new SCIP flap variation, the "extended" or "direct" SCIP flap, to effectively reconstruct a wide scrotal defect after a traumatic injury. The "extended" SCIP flap is designed medial and cranial to the anterosuperior iliac spine (ASIS) using the superficial branch of the SCIA as the main pedicle.

The effects of white matter hyperintensities on MEG power spectra in cognitively healthy aging.

Objective: This study sought to identify magnetoencephalography (MEG) power spectra patterns associated with cerebrovascular damage (white matter hyperintensities - WMH) and their relationship with cognitive performance and brain structure integrity in aging individuals without cognitive impairment. Methods: We hypothesized a "slowness" pattern characterized by increased power in δ and θ bands and decreased power in the ß band associated with the severity of vascular damage. MEG signals were analyzed in cognitively healthy older adults to investigate these associations. Results: Contrary to expectations, we did not observe an increase in δ and θ power. However, we found a significant negative correlation between ß band power and WMH volume. This ß power reduction was linked to structural brain changes, such as larger lateral ventricles, reduced white matter volume, and decreased fractional anisotropy in critical white matter tracts, but not to cognitive performance. This suggests that ß band power reduction may serve as an early marker of vascular damage before the onset of cognitive symptoms. Conclusion: Our findings partially confirm our initial hypothesis by demonstrating a decrease in ß band power with increased vascular damage but not the anticipated increase in slow band power. The lack of correlation between the ßpow marker and cognitive performance suggests its potential utility in early identification of at-risk individuals for future cognitive impairment due to vascular origins. These results contribute to understanding the electrophysiological signatures of preclinical vascular damage and highlight the importance of MEG in detecting subtle brain changes associated with aging.

Pyogenic liver abscess caused by an atypical hypervirulent Klebsiella pneumoniae K1-ST23 in Mexico.

Hypervirulent K. pneumoniae infection has been raising worldwide and is one of the major causes of community-acquired pyogenic liver abscess. We described a case report of pyogenic liver abscess caused by an atypical hypervirulent (non-hypermucoviscous) K. pneumoniae K1 ST23 in a diabetic Asian patient who resided in Mexico. The susceptibility to antimicrobials, pathogenicity, molecular and genomic analysis were determined. A man from Guangdong (China) with a recent diagnosis of diabetes mellitus was admitted to the hospital, and he denied traveling in the last 3 months. A computed tomography revealed a right lobe liver abscess. On the third day after admission a Klebsiella pneumoniae isolate (14652) was obtained. The isolate corresponded to a susceptible K. pneumoniae with capsular type K1 and ST23 (CG23) and exhibited a non-hypermucoviscous phenotype. The isolate 14652 was genetically related to the globally distributed lineage ST23-KL1. This study describes the first case in Mexico of K. pneumoniae capsular type K1 and ST23 with an atypical hypervirulent phenotype.

Genomic and mutational profiling of ductal carcinomas in situ and matched adjacent invasive breast cancers reveals intra-tumour genetic heterogeneity and clonal selection.

The mechanisms underlying the progression from ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) of the breast are yet to be fully elucidated. Several hypotheses have been put forward to explain the progression from DCIS to IDC, including the selection of a subpopulation of cancer cells with specific genetic aberrations, and the acquisition of new genetic aberrations or non-genetic mechanisms mediated by the tumour microenvironment. To determine whether synchronously diagnosed ipsilateral DCI and IDCs have modal populations with distinct repertoires of gene copy number aberrations and mutations in common oncogenes, matched frozen samples of DCIS and IDC were retrieved from 13 patients and subjected to microarray-based comparative genomic hybridization (aCGH) and Sequenom MassARRAY (Oncocarta v 1.0 panel). Fluorescence in situ hybridization and Sanger sequencing were employed to validate the aCGH and Sequenom findings, respectively. Although the genomic profiles of matched DCI and IDCs were similar, in three of 13 matched pairs amplification of distinct loci (ie 1q41, 2q24.2, 6q22.31, 7q11.21, 8q21.2 and 9p13.3) was either restricted to, or more prevalent in, the modal population of cancer cells of one of the components. Sequenom MassARRAY identified PIK3CA mutations restricted to the DCIS component in two cases, and in a third case the frequency of the PIK3CA mutant allele reduced from 49% in the DCIS to 25% in the IDC component. Despite the genomic similarities between synchronous DCIS and IDC, our data provide strong circumstantial evidence to suggest that in some cases the progression from DCIS to IDC is driven by the selection of non-modal clones that harbour a specific repertoire of genetic aberrations.

Overview of Systematic Reviews of Health Interventions for the Prevention and Treatment of Overweight and Obesity in Children.

(1) Background: The importance of studying the health interventions used to prevent and treat overweight and obesity in school-aged children is imperative. This overview aimed to summarize systematic reviews that assess the effects of school-based, family, and mixed health interventions for preventing and treating overweight and obesity in school-aged children. (2) Methods: The Cochrane Collaboration methodology and PRISMA statement were followed. A search was conducted using terms adapted to 12 databases. Systematic reviews reporting interventions in children from six to 12 years old with an outcome related to preventing or treating obesity and overweight were included. Studies with pharmacological or surgical interventions and adolescents were excluded. (3) Results: A total of 15,226 registers were identified from databases and citation searching. Of those, ten systematic reviews published between 2013 and 2022 were included. After the overlap, 331 interventions for children between 6 and 12 years old were identified, and 61.6% involved physical activity and nutrition/diet intervention. Multicomponent intervention, combining physical activity with nutrition and behavioral change, school-based plus community-based interventions may be more effective in reducing overweight and obesity in children. (4) Conclusions: Plenty of interventions for childhood overweight and obesity aimed at prevention and treatment were identified, but there is a gap in the methodological quality preventing the establishment of a certain recommendation.

Association of candidate genetic variants and circulating levels of ApoE/ApoJ with common neuroimaging features of cerebral amyloid angiopathy.

Introduction: Cerebral amyloid angiopathy (CAA) is characterized by the accumulation of amyloid-ß (Aß) in brain vessels and is a main cause of lobar intracerebral hemorrhage (ICH) in the elderly. CAA is associated with magnetic resonance imaging (MRI) markers of small vessel disease (SVD). Since Aß is also accumulated in Alzheimer's disease (AD) in the brain parenchyma, we aimed to study if several single nucleotide polymorphisms (SNPs) previously associated with AD were also associated with CAA pathology. Furthermore, we also studied the influence of APOE and CLU genetic variants in apolipoprotein E (ApoE) and clusterin/apolipoprotein J (ApoJ) circulating levels and their distribution among lipoproteins. Methods: The study was carried out in a multicentric cohort of 126 patients with lobar ICH and clinical suspicion of CAA. Results: We observed several SNPs associated with CAA neuroimaging MRI markers [cortical superficial siderosis (cSS), enlarged perivascular spaces in the centrum semiovale (CSO-EPVS), lobar cerebral microbleeds (CMB), white matter hyperintensities (WMH), corticosubcortical atrophy and CAA-SVD burden score]. Concretely, ABCA7 (rs3764650), CLU (rs9331896 and rs933188), EPHA1 (rs11767557), and TREML2 (rs3747742) were significantly associated with a CAA-SVD burden score. Regarding circulating levels of apolipoproteins, protective AD SNPs of CLU [rs11136000 (T) and rs9331896 (C)] were significantly associated with higher HDL ApoJ content in the lobar ICH cohort. APOEε2 carriers presented higher plasma and LDL-associated ApoE levels whereas APOEε4 carriers presented lower plasma ApoE levels. Additionally, we observed that lower circulating ApoJ and ApoE levels were significantly associated with CAA-related MRI markers. More specifically, lower LDL-associated ApoJ and plasma and HDL-associated ApoE levels were significantly associated with CSO-EPVS, lower ApoJ content in HDL with brain atrophy and lower ApoE content in LDL with the extent of cSS. Discussion: This study reinforces the relevance of lipid metabolism in CAA and cerebrovascular functionality. We propose that ApoJ and ApoE distribution among lipoproteins may be associated with pathological features related to CAA with higher ApoE and ApoJ levels in HDL possibly enhancing atheroprotective, antioxidative, and anti-inflammatory responses in cerebral ß-amyloidosis.

Safety and efficacy of intra-arterial bone marrow mononuclear cell transplantation in patients with acute ischaemic stroke in Spain (IBIS trial): a phase 2, randomised, open-label, standard-of-care controlled, multicentre trial.

BACKGROUND: Pilot clinical trials have shown the safety of intra-arterial bone marrow mononuclear cells (BMMNCs) in stroke. However, the efficacy of different doses of intra-arterial BMMNCs in patients with acute stroke has not been tested in a randomised clinical trial. We aimed to show safety and efficacy of two different doses of autologous intra-arterial BMMNC transplantation in patients with acute stroke. METHODS: The IBIS trial was a multicentre phase 2, randomised, controlled, investigator-initiated, assessor-blinded, clinical trial, in four stroke centres in Spain. We included patients (aged 18-80 years) with a non-lacunar, middle cerebral artery ischaemic stroke within 1-7 days from stroke onset and with a National Institutes of Health Stroke Scale score of 6-20. We randomly assigned patients (2:1:1) with a computer-generated randomisation sequence to standard of care (control group) or intra-arterial injection of autologous BMMNCs at one of two different doses (2 × 106 BMMNCs/kg or 5 × 106 BMMNCs/kg). The primary efficacy outcome was the proportion of patients with modified Rankin Scale scores of 0-2 at 180 days in the intention-to-treat population, comparing each BMMNC dose group and the pooled BMMNC group versus the control group. The primary safety endpoint was the proportion of serious adverse events. This trial was registered at ClinicalTrials.gov, NCT02178657 and is completed. FINDINGS: Between April 1, 2015, and May 20, 2021, we assessed 114 patients for eligibility. We randomly assigned 77 (68%) patients: 38 (49%) to the control group, 20 (26%) to the low-dose BMMNC group, and 19 (25%) the high-dose BMMNC group. The mean age of participants was 62·4 years (SD 12·7), 46 (60%) were men, 31 (40%) were women, all were White, and 63 (82%) received thrombectomy. The median NIHSS score before randomisation was 12 (IQR 9-15), with intra-arterial BMMNC injection done a median of 6 days (4-7) after stroke onset. The primary efficacy outcome occurred in 14 (39%) patients in the control group versus ten (50%) in the low-dose group (adjusted odds ratio 2·08 [95% CI 0·55-7·85]; p=0·28), eight (44%) in the high-dose group (1·89 [0·52-6·96]; p=0·33), and 18 (47%) in the pooled BMMNC group (2·22 [0·72-6·85]; p=0·16). We found no differences in the proportion of patients who had adverse events or dose-related events, but two patients had a groin haematoma after cell injection in the low-dose BMMNC group. INTERPRETATION: Intra-arterial BMMNCs were safe in patients with acute ischaemic stroke, but we found no significant improvement at 180 days on the mRS. Further clinical trials are warranted to investigate whether improvements might be possible at different timepoints. FUNDING: Instituto de Salud Carlos III co-funded by the European Regional Development Fund/European Social Fund, Mutua Madrileña, and the Regional Ministry of Health of Andalusia.

[The influence of climate on the onset of intracranial hemorrhages]. / Variaciones climáticas y hemorragias intracraneales.

BACKGROUND: there are not studies exploring the potential role of weather conditions in the incidence of intracranial hemorrhages in Latin America. METHODS: a descriptive study was carried out in an emergency room from Cartagena de Indias (Colombia). Data for all adult patients with intracranial hemorrhage and meteorological variables of the days when intracranial hemorrhages occurred were recorded and compared to with those where not a single case. RESULTS: the differences between the average temperature, maximum and minimum temperatures, barometric pressure, relative humidity and wind speed were non statistically significant. However, when comparing the temperature differences day of the event over the previous days, those met the pre-established criteria of statistical significance. Furthermore, differences in barometric pressure, relative humidity, maximum and minimum temperature over the previous day, also reached this criterion. CONCLUSIONS: the results of this study suggest the existence of a climatic profile associated with the onset of intracranial hemorrhages.

[Brain stem compression preceded by trigeminal neuralgia in a patient with vertebro-basilar and bilateral carotid dolichoectasia]. / Compresión tronco-encefálica precedida por neuralgia del trigémino en un paciente con dolicoectasia vertebro-basilar y carotidea bilateral.

We described a patient who had left trigeminal neuralgia by vertebro-basilar dolichoectasia, who underwent microvascular decompression separating the basilar artery of the trigeminal nerve by interposing a vascular graft piece. Symptoms resolved completely after surgery. Nine years later, he has a recurrence of facial pain associated with rapidly progressive brainstem compressive symptoms. The brain MRI showed the vertebro-basilar dolichoectasia exerting compression on the ventral-lateral aspect of the pons and the medulla. In cerebral angiography confirmed the presence of dilated tortuous vertebral arteries, basilar, and of both internal carotid. To our knowledge this is the first case of brain stem compression syndrome preceded by NT in patients with vertebro-basilar dolichoectasia and one of the few cases with coexistence of vertebro-basilar and bilateral carotid dolichoectasia.

[Intracerebral hemorrhages following drainage of chronic subdural hematomas]. / Hemorragia intracerebral posterior a drenado de hematomas subdurales crónicos.

BACKGROUND: postoperative intracerebral hemorrhage after drainage of chronic subdural hematoma is a rarely reported complication; however, its incidence, according to different series may be underestimated. CASE REPORT: this report presents a 77 year old male patient who, after the drainage of bilateral chronic subdural hematomas, developed an extensive hemorrhage in the thalami, basal ganglia, midbrain and pons, with extension into the ventricles and obstructive hydrocephalus. CONCLUSIONS: compression by extra-axial collection decreases cerebral blood flow on the affected hemisphere and alters its vascular self-adjustment. The rapid increase in cerebral blood flow in brain areas with altered vascular self-adjustment appears to be the precipitating mechanism of intracerebral hemorrhage after surgical evacuation of chronic subdural hematomas.