How to reduce the complication rate of multiple burr holes surgery in moyamoya angiopathy.

PURPOSE: This study is aimed at analyzing clinical outcome, absence of stroke recurrence, revascularization, and complications and long-term follow-up in the surgical treatment of moyamoya angiopathy (MMA) using the multiple burr holes (MBH) technique with dura opening and arachnoid preservation as a single procedure. To the best of our knowledge, this is the first to describe an MBH technique with arachnoid preservation. METHOD: We retrospectively reviewed all patients operated from June 2001 to March 2021, for a symptomatic and progressive MMA operated with opening of the dura but arachnoid preservation. Clinical examinations were obtained in all patients, and radiological monitoring was performed by cerebral 3D-magnetic resonance angiography (MRA) with perfusion or single-photon emission computed tomography (SPECT) with acetazolamide. RESULTS: In total, 21 consecutive patients (6 children and 15 adults) were included with a mean age of 7.4 years in the pediatric group and 36.9 years in the adult group. Initial presentation was permanent ischemic stroke in 15 cases, transient ischemic attack (TIA) in 5 cases, and cerebral hemorrhage in one case. The MBH with dura opening and arachnoid preservation was performed bilaterally in 9 cases (43%) and unilaterally in 12 cases (57%). One patient died due to intraoperative bilateral ischemic stroke. Of the 20 other patients, 30% demonstrated clinical stability and 70% showed partial or complete recovery. Although one patient experienced a perioperative stroke, we did not observe any pseudomeningocele or postoperative ischemic stroke (IS) recurrence in all surviving cases during the average follow-up period of 55.5 months (range: 1-195). These outcomes emphasize the importance of preoperative monitoring to ensure the effectiveness and safety of the intervention. Postoperative angiography studies showed revascularization in 96.3% of treated hemispheres (100% in the adult group vs 80% in the pediatric group). CONCLUSIONS: Our results on this small cohort suggest that the MBH technique with opening of the dura and arachnoids preservation can prevent recurrent strokes and reduce the risk of pseudomeningocele.

Boar sperm motility is modulated by CCK at a low concentration of bicarbonate under capacitation conditions.

In a previous study, our group detected the cholecystokinin (CCK) protein in the porcine oviduct. This fact, together with the involvement of CCK in the regulation of sperm protein tyrosine phosphorylation by the modulation of HCO3 - uptake (in mice and humans) suggests a role for CCK during sperm capacitation. Therefore, on the one hand, the expression of CCK receptors (CCK1R and CCK2R) on boar testes has been investigated and probed; on the other hand, boar spermatozoa (from seminal doses of 1-day and 5-day storage) were exposed to different concentrations of CCK (0-control, 25 or 50 µM) in a medium supporting capacitation supplemented with 0, 5 or 25 mmol/L of HCO3 - for 1 h at 38.5°C. Sperm motion (total and progressive motility), kinetic parameters, viability, acrosome status, and mitochondrial activity were determined. No differences between groups (0, 25 or 50 µM of CCK) were observed when HCO3 - was absent in the media (p > .05). However, the results showed that when the media was supplemented with 5 mmol/L HCO3 - in 1-day seminal dose storage, the linearity index (LIN, %), straightness index (STR, %) and oscillation index (WOB, %) (sperm kinetics parameters) increased in the presence of CCK regardless the concentration (p < .05). Nevertheless, CCK in sperm from 5-day storage only increased the WOB parameter in comparison to the control (p < .05). Furthermore, the average amplitude of the lateral displacement of the sperm head (ALH, µm) and curvilinear velocity (VCL, µm/s) decreased when CCK was present, depending on its concentration and sperm aging (1-day vs. 5-days) (p < .05). In the case of the media supporting capacitation supplemented with 25 mmol/L HCO3 - , any differences were observed except for sperm viability in the 5-day seminal doses, which increased in the 50 µM-CCK group compared to the control (p < .05). In conclusion, these data suggest an implication of CCK protein during sperm capacitation under low bicarbonate concentration increasing the sperm linear trajectory.

Potential effect of chloroquine and propranolol combination to treat colorectal and triple-negative breast cancers.

Drug repositioning explores the reuse of non-cancer drugs to treat tumors. In this work, we evaluated the effect of the combination of chloroquine and propranolol on colorectal and triple-negative breast cancers. Using as in vitro models the colorectal cancer cell lines HCT116, HT29, and CT26, and as triple-negative breast cancer models the 4T1, M-406, and MDA-MB-231 cell lines, we evaluated the effect of the drugs combination on the viability, apoptosis, clonogenicity, and cellular migratory capacity. To explore the in vivo effects of the combination on tumor growth and metastasis development we employed graft models in BALB/c, nude, and CBi mice. In vitro studies showed that combined treatment decreased cell viability in a dose-dependent manner and increased apoptosis. Also, we demonstrated that these drugs act synergically and that it affects clonogenicity and migration. In vivo studies indicated that this drug combination was effective on colorectal models but only partially on breast cancer. These results contributed to the search for new and safe treatments for colorectal and triple-negative carcinomas.

Efectividad del bloqueo de nervios cluneales para tratamiento de dolor lumbar crónico / Effectiveness of cluneal nerve block for the treatment of chronic low back pain

Introducción: El dolor lumbar representa una problemática de salud pública ante la discapacidad que genera, sea motora o sensitiva de etiología multifactorial, en la cual el atrapamiento de los nervios cluneales cumple un papel importante, encontrando como una alternativa al dolor por esta patología el manejo intervencionista. El objetivo principal del estudio fue establecer la efectividad del bloqueo de nervios cluneales en dolor lumbar crónico en pacientes mayores de 18 años de dos hospitales de Bogotá.Métodos: Estudio de tipo observacional, retrospectivo, realizado en pacientes diagnosticados con dolor lumbar crónico y signos y síntomas de atrapamiento de nervios cluneales o clunealgía llevados a bloqueo de nervios cluneales en quienes que se evaluó la intensidad del dolor y duración del efecto analgésico en cuatro momentos.Resultados: Se identificaron 45 pacientes; de estos, 11 no presentaban datos de seguimiento. El 93 % (n = 35) de los pacientes presentaron una EVA (escala visual análoga del dolor) mayor a 7 previo al procedimiento, el 28 % (n = 11) presentaron postbloqueo inmediato mejoría del dolor con una EVA menor a 6, en el primer control el 57 % (n = 22) conservaron la mejoría alcanzada, y el 10 % (n = 4) retornó a su estado basal de dolor. En el segundo, el 10 % (n = 4) de los pacientes no presentaron cambios en la intensidad, y el 78,9 % (n = 30) conservaba mejoría en la intensidad del dolor.Conclusiones: El bloqueo de los nervios cluneales es una alternativa vanguardista de manejo transitorio del dolor lumbar crónico que permitirá seleccionar con mayor objetividad los pacientes candidatos a intervencionismo guiado por fluoroscopia. Se propone la realización de estudios mediante estudios tipo III como los ensayos aleatorizados con grupos donde se administre placebo versus mezclas analgésicas en pacientes con clunealgia.(AU)

Introduction: Low back pain represents a public health problem due to the disability it generates, whether motor or sensory, of multifactorial etiology, in which cluneal nerve entrapment plays an important role, finding an alternative to pain from this pathology. interventional management. The main objective of the study was to establish the efficacy of cluneal nerve block in chronic low back pain in patients older than 18 years from two hospitals in Bogotá.Methods: Observational, retrospective study, carried out in patients diagnosed with chronic low back pain and signs and symptoms of cluneal nerve entrapment or clunealgia leading to cluneal nerve block in whom pain intensity and duration of the analgesic effect were evaluated in four moments.Results: 45 patients were identified; of these, 11 did not present follow-up data. 93 % (n = 35) of the patients presented a VAS (visual analogue pain scale) greater than 7 prior to the procedure, 28 % (n = 11) presented immediate post-block pain improvement with a VAS less than 6, 57 % at the first control (n = 22) maintained the improvement achieved, and 10 % (n = 4) returned to their baseline state of pain. In the second, 10 % (n = 4) of the patients did not show changes in intensity, and 78.9 % (n = 30) maintained improvement in pain intensity.Conclusions: Cluneal nerve blocks are an avant-garde alternative for the temporary management of chronic low back pain that will make it possible to more objectively select patients who are candidates for fluoroscopy-guided intervention. Studies are proposed using type III studies such as randomized trials with groups where placebo is administered versus analgesic mixtures in patients with clunealgia.(AU)

Genetic variants associated with steatohepatitis and liver fibrosis in HIV-infected patients with NAFLD.

Background and aims: Nonalcoholic fatty liver disease (NAFLD) is a common cause of liver damage in people living with HIV (PLWHIV). Several studies have investigated candidate genes for susceptibility to NAFLD and to steatohepatitis. PNPLA3, TM6SF2, and MBOAT7-TMC4 have been reported to be associated with elevated ALT levels and the histologic parameters of nonalcoholic steatohepatitis and severity of fibrosis. Our objective was to analyze the relationship between PNPLA3, TM6SF2, and MBOAT7-TMC4 and steatosis, steatohepatitis, and liver fibrosis in PLWHIV with NAFLD. Method: A cohort of PLWHIV with persistently elevated aminotransferase levels and suspected NAFLD who underwent liver biopsy and determination of genetic variants was assessed at two large centers in Spain. All participants included in the current study were genotyped for rs738409 (PNPLA3), rs58542926 (TM6SF2), and rs641738 (MBOAT7-TMC4). Results: The study population comprised PLWHIV who were on stable antiretroviral therapy [7.7% women; median age, 49.3 years (44-53.4)]. The median CD4 count was 829 (650-980), 60% had metabolic syndrome, and 18.5% were diabetic. The median BMI was 28.9 (25.5-30.8). Patients with liver steatosis (any grade) vs. nonsteatosis tended to harbor the PNPLA3 G allele variant [57.6% vs. 16.7% (p = 0.09)], but not TM6SF2 or MBOAT7-TMC4 variants. However, those with steatohepatitis vs. nonsteatohepatitis significantly more frequently had the PNPLA3 G allele variant [69.4% vs. 39.1% (p < 0.05)] and the MBOAT7-TMC4 A allele variant [75% vs. 42% (p < 0.05)]. In our cohort, the TM6SF2 gene variant was not associated with steatosis or steatohepatitis. The PNPLA3 G allele variant was associated with steatohepatitis [OR 4.9 (1.3-18); p 0.02] and liver fibrosis [OR 4.3 (1.1-17.4); p 0.04], and the MBOAT7-TMC4 A allele variant was associated with steatohepatitis [OR 6.6 (1.6-27.6); p 0.01]. Conclusion: The PNPLA3 G allele variant and MBOAT7-TMC4 A allele variant were associated with steatohepatitis and liver fibrosis in PLWHIV with persistently elevated aminotransferases and NAFLD. We recommend routine genotyping for PNPLA3 and MBOAT7-TMC4 in PLWHIV with NAFLD to identify those at higher risk of progression.

Assessment of Noninvasive Markers of Steatosis and Liver Fibrosis in Human Immunodeficiency Virus-Monoinfected Patients on Stable Antiretroviral Regimens.

Background: Nonalcoholic fatty liver disease (NAFLD) is a major nonacquired immune deficiency syndrome-defining condition for persons with human immunodeficiency virus (PWH). We aimed to validate noninvasive tests for the diagnosis of NAFLD in PWH. Methods: This is a cross-sectional study of PWH on stable antiretroviral therapy with persistently elevated transaminases and no known liver disease. The area under the receiver operating characteristic curve (AUROC) was calculated to compare the diagnostic accuracy of liver biopsy with abdominal ultrasound, transient elastography (TE) (including controlled attenuation parameter [CAP]), and noninvasive markers of steatosis (triglyceride and glucose index [TyG], hepatic steatosis index [HSI], fatty liver index [FLI]) and fibrosis ([FIB]-4, aminotransferase-to-platelet ratio index [APRI], NAFLD fibrosis score). We developed a diagnostic algorithm with serial combinations of markers. Results: Of 146 patients with increased transaminase levels, 69 underwent liver biopsy (90% steatosis, 61% steatohepatitis, and 4% F ≥3). The AUROC for steatosis was as follows: ultrasound, 0.90 (0.75-1); CAP, 0.94 (0.88-1); FLI, 0.81 (0.58-1); HSI, 0.74 (0.62-0.87); and TyG, 0.75 (0.49-1). For liver fibrosis ≥F3, the AUROC for TE, APRI, FIB-4, and NAFLD fibrosis score was 0.92 (0.82-1), 0.96 (0.90-1), 0.97 (0.93-1), and 0.85 (0.68-1). Optimal diagnostic performance for liver steatosis was for 2 noninvasive combined models of tests with TyG and FLI/HSI as the first tests and ultrasound or CAP as the second tests: AUROC = 0.99 (0.97-1, P < .001) and 0.92 (0.77-1, P < .001). Conclusions: Ultrasound and CAP performed best in diagnosing liver steatosis, and FLI, TyG, and HSI performed well. We propose an easy-to-implement algorithm with TyG or FLI as the first test and ultrasound or CAP as the second test to accurately diagnose or exclude NAFLD.

Association between benzodiazepine receptor agonist use and mortality in patients hospitalised for COVID-19: a multicentre observational study.

AIMS: To examine the association between benzodiazepine receptor agonist (BZRA) use and mortality in patients hospitalised for coronavirus disease 2019 (COVID-19). METHODS: A multicentre observational study was performed at Greater Paris University hospitals. The sample involved 14 381 patients hospitalised for COVID-19. A total of 686 (4.8%) inpatients received a BZRA at hospital admission at a mean daily diazepam-equivalent dose of 19.7 mg (standard deviation (s.d.) = 25.4). The study baseline was the date of admission, and the primary endpoint was death. We compared this endpoint between patients who received BZRAs and those who did not in time-to-event analyses adjusted for sociodemographic characteristics, medical comorbidities and other medications. The primary analysis was a Cox regression model with inverse probability weighting (IPW). RESULTS: Over a mean follow-up of 14.5 days (s.d. = 18.1), the primary endpoint occurred in 186 patients (27.1%) who received BZRAs and in 1134 patients (8.3%) who did not. There was a significant association between BZRA use and increased mortality both in the crude analysis (hazard ratio (HR) = 3.20; 95% confidence interval (CI) = 2.74-3.74; p < 0.01) and in the IPW analysis (HR = 1.61; 95% CI = 1.31-1.98, p < 0.01), with a significant dose-dependent relationship (HR = 1.55; 95% CI = 1.08-2.22; p = 0.02). This association remained significant in sensitivity analyses. Exploratory analyses indicate that most BZRAs may be associated with an increased mortality among patients hospitalised for COVID-19, except for diazepam, which may be associated with a reduced mortality compared with any other BZRA treatment. CONCLUSIONS: BZRA use may be associated with an increased mortality among patients hospitalised for COVID-19, suggesting the potential benefit of decreasing dose or tapering off gradually these medications when possible.

Changes of CD3+CD56+ γδ T cell number and apoptosis during hospital admission are related to mortality in septic patients.

Immunoparalysis and apoptosis of T cells are serious problems for the evolution of septic patients. We aimed to relate changes in the number of αß and γδ T cells during hospital stay to the poor evolution of sepsis. In this prospective study, we recruited a total of 92 septic patients from the Emergency and Intensive Care Departments of two Hospitals, according to the latest criteria for the definition and management of sepsis. According to the severity of the septic process, there was a progressive decrease in T cells, being much more intense in γδ T cells. This decrease recovered in surviving patients, but CD3+CD56+ γδ T cells continued to decreased during hospital stay in non-surviving patients. Apoptosis increased in sepsis. Cell death of CD3+CD56+ γδ T cells progressively increased according to the severity of sepsis, especially in non-surviving patients.

The SARS-CoV-2 first wave impact in the acute inflammatory surgical pathologies.

Anecdotal evidence suggests that community infection control measures during the COVID-19 outbreak have modified the number and natural history of acute surgical inflammatory processes (ASIP-appendicitis, cholecystitis, diverticulitis and perianal abscesses) admissions. This study aims to evaluate the impact of the COVID-19 pandemic on the presentation and treatment ASIP and quantify the effect of COVID-19 infection on the outcomes of ASIP patients. This was a multicentre, comparative study, whereby ASIP cases from 2019, 2020 and 2021 (March 14th to May 2nd) were analyzed. Data regarding patient and disease characteristics as well as outcomes, were collected from sixteen centres in Madrid, and one in Seville (Spain). The number of patients treated for ASIP in 2019 was 822 compared to 521 in 2020 and 835 in 2021. This 1/3rd reduction occurs mainly in patients with mild cases, while the number of severe cases was similar. Surgical standards suffered a step back during the first wave: Lower laparoscopic approach and longer length of stay. We also found a more conservative approach to the patients this year, non-justified by clinical circumstances. Luckily these standards improved again in 2021. The positive COVID-19 status itself did not have a direct impact on mortality. Strikingly, none of the 33 surgically treated COVID positive patients during both years died postoperatively. This is an interesting finding which, if confirmed through future research with a larger sample size of COVID-19 positive patients, can expedite the recovery phase of acute surgical services.

Repositioning metformin and propranolol for colorectal and triple negative breast cancers treatment.

Drug repositioning refers to new uses for existing drugs outside the scope of the original medical indications. This approach fastens the process of drug development allowing finding effective drugs with reduced side effects and lower costs. Colorectal cancer (CRC) is often diagnosed at advanced stages, when the probability of chemotherapy resistance is higher. Triple negative breast cancer (TNBC) is the most aggressive type of breast cancer, highly metastatic and difficult to treat. For both tumor types, available treatments are generally associated to severe side effects. In our work, we explored the effect of combining metformin and propranolol, two repositioned drugs, in both tumor types. We demonstrate that treatment affects viability, epithelial-mesenchymal transition and migratory potential of CRC cells as we described before for TNBC. We show that combined treatment affects different steps leading to metastasis in TNBC. Moreover, combined treatment is also effective preventing the development of 5-FU resistant CRC. Our data suggest that combination of metformin and propranolol could be useful as a putative adjuvant treatment for both TNBC and CRC and an alternative for chemo-resistant CRC, providing a low-cost alternative therapy without associated toxicity.

Planetary ball-mill as a versatile tool to controlled potato starch modification to broaden its industrial applications.

Pure potato starch has been modified by high-energy-ball-milling as a function of energy supplied, aiming to obtain products for different possibilities of industrial application. Burgios's equation has been used to calculate the energy supplied. The effect of the milling has been followed by a characterization of the starch morphology, crystallinity, solubility, swelling, retrogradation, viscosity, apparent viscosity, functional groups, and reducing sugar concentration. The high-energy-ball-milling not only changes the physical properties but also induces the mechanolysis of potato starch, breaking the glycosidic linkages of the starch molecules. A representation of the possible mechanism of starch mechanolysis is proposed. Three stages of the transformation of potato starch through high-energy ball-milling can be identified. Each of these stages generates starch with properties that can be used in different industrial applications.

Anterior thalamic nucleus deep brain stimulation for refractory epilepsy: Preliminary results in our first 5 patients.

OBJECTIVES: Deep brain stimulation (DBS) of the anterior thalamic nucleus (ATN) has been recognized to be an efficient treatment of refractory epilepsy (RE). However, ATN targeting is difficult and up to 8% of lead misplacement is reported. Our objective is to report our surgical procedure based on MRI targeting and our clinical results. PATIENTS AND METHODS: Our first five consecutive patients (4M, 1F, mean age: 42.8 years) treated by DBS of ATN between March and October 2016 were included. The mean duration of their epilepsy was 29 years. Four patients had already vagal nerve stimulation and 2 mammillary body stimulation. Stereotactic coordinates were calculated using distal segment of mammillothalamic tract as landmark. All procedures were performed under general anesthesia with intraoperative control of lead position using a robotic 3D fluoroscopy and image fusion with the preoperative MRI. RESULTS: No complications or lead misplacement was observed. The mean 3D distance between the planned target and location of the lead was 1.8 mm. Each patient was followed up at least one year (15+3months). The stimulation parameters were: 140Hz, 90m/s and 5 Volts with one minute ON/five minutes OFF cycle. The mean reduction of seizure frequency reached -52.5% (+32.2) at 6-months but decreased to -24.5% (+65.7) at the last follow-up due to some adverse events not related to stimulation. CONCLUSION: No complication, no lead misplacement and the improvement in our first patients, previously not help by multiple medications or surgeries, are encouraging.

How to integrate stereotactic body radiation therapy and hypofractionation in the management of stage III lung cancer in the age of immunotherapy.

The constant advances in the field of lung cancer immunotherapy have recently reached the treatment of locally advanced disease with the approval of durvalumab after concurrent chemoradiation. However, radiation therapy continues to be key for controlling the disease at this stage. Over the years, different strategies have been employed to try to optimize outcomes using radiotherapy, with cardiac and pulmonary toxicity as the main limitation on its success. The interest in the use of hypofractionation and stereotactic body radiation therapy for stage III non-small cell lung cancer has increased as knowledge regarding these kinds of treatments has been enhanced. Hypofractionation is a relatively frequent treatment, although the level of evidence that supports it is limited. For its part, stereotactic body radiation therapy has been particularly studied as a boost after chemoradiation, with encouraging results. In both cases, study of how to integrate these tools with chemotherapy and particularly with immunotherapy is essential, as they may have an immunomodulatory role.

Inhibition effect of polyurethane foam waste in dioxin formation.

The present work has been focused on studying the polychlorinated polychlorodibenzo-p-dioxin/furan (PCDD/F) inhibition in the combustion process by prior addition of an inhibitor to the fuel. Three different experiments of combustion were carried out at 850 °C in a laboratory-scale horizontal tubular quartz reactor, and several compounds were analyzed from the flue gas obtained, such as PCDD/Fs, dioxin-like polychlorinated biphenyls (dl-PCBs), NH3, HCN, NOx, HCl, Cl2, chlorobenzenes (ClBzs), chlorophenols (ClPhs), polycyclic aromatic hydrocarbons (PAHs), volatile and other semivolatile organic compounds. The fuel used was a synthetic waste which was composed of sawdust and PVC (95 wt% and 5 wt%, respectively) and the inhibitors studied were polyurethane foam (PUF) that can be found in mattress waste and gases from the oxidative pyrolysis of PUF. Due to the high N content of PUF, a significant decrease of PCDD/F and dl-PCB formation has been obtained in the experimental runs carried out with the inhibitors studied, particularly with the gases from the oxidative pyrolysis of PUF. In addition, it must be noted that emissions of incomplete combustion products have also decreased.