Validity of estimated aortic pulse wave velocity measured during the 6-min walk test to predict anaerobic fitness before major non-cardiac surgery.

BACKGROUND: This study aimed to assess the efficacy of estimated preoperative aortic pulse wave velocity (AoPWV) to discriminate between low and high 6 min walk test (6MWT) distance in patients awaiting major non-cardiac surgery. METHODS: Prospective observational study in 133 patients undergoing non cardiac surgery. AoPWV and the distance walked during a 6MWT were assessed. Receiver operating characteristic (ROC) curve analysis was used to determine two different AoPWV cut-points for predicting a distance of 427 m in the 6MWT. We also calculated lower and upper AoPWV cut-points (probability ≥ 0.75) for predicting a distance of < 427 m, ≥427 m, and also 563 m in the 6MWT. RESULTS: The ROC curve analysis for the < 427 m distance revealed an area under the curve (AUC) of 0.68 (95% confidence interval 0.56-0.79) and an AUC of 0.72 (95% confidence interval 0.61-0.83) for >563 m. Patients with AoPWV > 10.97 m/s should be considered high risk, while those with <9.42 m/s can be considered low risk. CONCLUSIONS: AoPWV is a simple, non-invasive, useful clinical tool for identifying and stratifying patients awaiting major non-cardiac surgery. In situations of clinical uncertainty, additional measures should be taken to assess the risk.

Intraoperative Goal-Directed Hemodynamic Therapy through Fluid Administration to Optimize the Stroke Volume: A Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: To evaluate the clinical impact of optimizing stroke volume (SV) through fluid administration as part of goal-directed hemodynamic therapy (GDHT) in adult patients undergoing elective major abdominal surgery. METHODS: This systematic review and meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and was registered in the PROSPERO database in January 2024. The intervention was defined as intraoperative GDHT based on the optimization or maximization of SV through fluid challenges, or by using dynamic indices of fluid responsiveness, including stroke volume variation, pulse pressure variation, and plethysmography variation index compared to usual fluid management. The primary outcome was postoperative complications. Secondary outcome variables included postoperative acute kidney injury (AKI), length of stay (LOS), intraoperative fluid administration, and 30-day mortality. RESULTS: A total of 29 randomized controlled trials (RCTs) met the inclusion criteria. There were no significant differences in the incidence of postoperative complications (RR 0.89; 95% CI, 0.78 to 1.00), postoperative AKI (OR 0.97; (95% IC, 0.55 to 1.70), and mortality (OR 0.80; 95% CI, 0.50 to 1.29). GDHT was associated with a reduced LOS compared to usual care (SMD: -0.17 [-0.32; - 0.03]). The subgroup in which hydroxyethyl starch was used for hemodynamic optimization was associated with fewer complications (RR 0.79; 95% CI, 0.65 to 0.94), whereas the subgroup of patients in whom crystalloids were used was associated with an increased risk of postoperative complications (RR 1.08; 95% CI, 1.04 to 1.12). CONCLUSIONS: In adults undergoing major surgery, goal-directed hemodynamic therapy focused on fluid-based stroke volume optimization did not reduce postoperative morbidity and mortality.

Detection of anti-HCV antibodies and risk factors in a population with access to public healthcare in Mexico.

INTRODUCTION AND AIM: Timely detection and diagnosis of hepatitis C virus (HCV) involves identifying the population that is predisposed to treatment and prevention, thus limiting complications and preventing infection. The aim of this study was to analyze and describe risk factors associated with anti-HCV antibody detection in a population with access to public healthcare that participated in a national screening program. MATERIAL AND METHODS: An analytic cross-sectional study was conducted that utilized data related to rapid tests carried out between September 2021 and October 2022 in 26 of the 32 states of Mexico. Anti-HCV reactive tests were selected, according to age and sex, for analyzing and comparing possible risk factors through descriptive and inferential statistics. The geographic distribution and density of the screening program at the state and municipal levels was analyzed. RESULTS: There were 75,185 anti-HCV antibody detections, 2,052 reactive tests, and mean participant age was 44.3 years (±15.1). Occupation: 32.3% were employees, 19% were housewives, and 18.2% were healthcare workers. Five out of every 10 cases had no indication of risk factors, but there was a 1.4 and 5-times greater likelihood of anti-HCV detection in men with a history of sharps injury or intravenous psychoactive substance use, compared with women. Regarding place of residence, 80% of the reactive tests were concentrated in the State of Mexico, Mexico City, and Guanajuato. CONCLUSIONS: The evidence herein helps determine the population and risk factors that should be focused on in carrying out the HCV microelimination strategy of continuous screening, diagnosis, medical treatment access, and epidemiologic surveillance.

Human gut microbiota analysis of cystic fibrosis infants using metaproteomics.

We report a metaproteomic analysis of the gut microbiota of eight infants with cystic fibrosis, during the first year of life. This is the first study in this disease that uses metaproteomics to analyze stool samples from patients at such a young age.

Efficient photocatalytic activity and selective adsorption of UiO-67 (Zr)/g-C3N4 composite toward a mixture of parabens.

In this study, UiO-67 (Zr)/g-C3N4 composites (U67N) were synthesized at wt.% ratios of 05:95, 15:85, and 30:70 using the solvothermal method at 80 °C for 24 h followed by calcination at 350 °C. The composites were characterized using UV-Vis diffuse reflectance spectroscopy, Fourier-transform infrared spectroscopy, photoluminescence spectroscopy, X-ray photoelectron spectroscopy, X-ray diffraction, scanning electron microscopy-energy-dispersive X-ray spectroscopy, transmission electron microscopy, and nitrogen physisorption analysis. In addition, thermal stability analysis of UiO-67 was conducted using thermogravimetric analysis. The photocatalytic performance of the composites was assessed during the degradation and mineralization of a mixture of methylparaben (MeP) and propylparaben (PrP) under simulated sunlight. The adsorption process of U67N 15:85 was characterized through kinetic studies and adsorption capacity experiments, which were modeled using pseudo-first-order and pseudo-second-order kinetics and Langmuir and Freundlich isotherms, respectively. The influence of pH levels 3, 5, and 7 on the photocatalytic degradation of the mixture was investigated, revealing enhanced degradation and mineralization at pH 3. The U67N composite exhibited dual capability in removing contaminants through adsorption and photocatalytic processes. Among the prepared composites, U67N 15:85 demonstrated the highest photocatalytic activity, achieving removal efficiencies of 96.8% for MeP, 92.5% for PrP, and 45.7% for total organic carbon in 300 kJ/m2 accumulated energy (3 h of reaction time). The detoxification of the effluent was confirmed through acute toxicity evaluation using the Vibrio fischeri method. The oxidation mechanism of the heterojunction formed between UiO-67 (Zr) and g-C3N4 was proposed based on PL analysis, photoelectrochemistry studies (including photocurrent response, Nyquist, and Mott-Schottky analyses), and scavenger assays.

Lipidomics signature in post-COVID patient sera and its influence on the prolonged inflammatory response.

BACKGROUND: The ongoing issues with post-COVID conditions (PCC), where symptoms persist long after the initial infection, highlight the need for research into blood lipid changes in these patients. While most studies focus on the acute phase of COVID-19, there's a significant lack of information on the lipidomic changes that occur in the later stages of the disease. Addressing this knowledge gap is critical for understanding the long-term effects of COVID-19 and could be key to developing personalized treatments for those suffering from PCC. METHODS: We employed untargeted lipidomics to analyze plasma samples from 147 PCC patients, assessing nearly 400 polar lipids. Data mining (DM) and machine learning (ML) tools were utilized to decode the results and ascertain significant lipidomic patterns. RESULTS: The study uncovered substantial changes in various lipid subclasses, presenting a detailed profile of the polar lipid fraction in PCC patients. These alterations correlated with ongoing inflammation and immune response. Notably, there were elevated levels of lysophosphatidylglycerols (LPGs) and phosphatidylethanolamines (PEs), and reduced levels of lysophosphatidylcholines (LPCs), suggesting these as potential lipid biomarkers for PCC. The lipidomic signatures indicated specific anionic lipid changes, implicating antimicrobial peptides (AMPs) in inflammation. Associations between particular medications and symptoms were also suggested. Classification models, such as multinomial regression (MR) and random forest (RF), successfully differentiated between symptomatic and asymptomatic PCC groups using lipidomic profiles. CONCLUSIONS: The study's groundbreaking discovery of specific lipidomic disruptions in PCC patients marks a significant stride in the quest to comprehend and combat this condition. The identified lipid biomarkers not only pave the way for novel diagnostic tools but also hold the promise to tailor individualized therapeutic strategies, potentially revolutionizing the clinical approach to managing PCC and improving patient care.

Final analysis of phase II results with cemiplimab in metastatic basal cell carcinoma after hedgehog pathway inhibitors.

BACKGROUND: Metastatic basal cell carcinoma (mBCC) is a rare condition with no effective second-line treatment options. Cemiplimab is an immune checkpoint inhibitor that blocks the binding of programmed cell death-1 (PD-1) to its ligands, programmed death-ligand 1 (PD-L1) and programmed death-ligand 2 (PD-L2). Here, we present the final analysis of cemiplimab in patients with mBCC after first-line hedgehog pathway inhibitor (HHI) treatment (NCT03132636). PATIENTS AND METHODS: In this open-label, single-arm, phase II study, adults with mBCC and Eastern Cooperative Oncology Group performance status ≤1, post-HHI treatment, received cemiplimab 350 mg intravenously every 3 weeks for ≤93 weeks or until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) by independent central review (ICR). Duration of response (DOR) was a key secondary endpoint. Other secondary endpoints were ORR per investigator assessment, progression-free survival (PFS), overall survival (OS), complete response rate, safety, and tolerability. RESULTS: Fifty-four patients were enrolled: 70% were male and the median age of patients was 64 [interquartile range (IQR) 57.0-73.0] years. The median duration of follow-up was 8 months (IQR 4-21 months). The ORR per ICR was 22% [95% confidence interval (CI) 12% to 36%], with 2 complete responses and 10 partial responses. Among responders, the median time to response per ICR was 3 months (IQR 2-7 months). The estimated median DOR per ICR was not reached [95% CI 10 months-not evaluable (NE)]. The disease control rate was 63% (95% CI 49% to 76%) per ICR and 70% (95% CI 56% to 82%) per investigator assessment. The median PFS per ICR was 10 months (95% CI 4-16 months); the median OS was 50 months (95% CI 28 months-NE). The most common treatment-emergent adverse events were fatigue [23 (43%)] and diarrhoea [20 (37%)]. There were no treatment-related deaths. CONCLUSIONS: Cemiplimab demonstrated clinically meaningful antitumour activity, including durable responses, and an acceptable safety profile in patients with mBCC who had disease progression on or intolerance to HHI therapy.

Exoftalmos y dolor ocular como presentación clínica de linfoma de Hodgkin con afectación intracraneal al diagnóstico / Exophthalmos and ocular pain as clinical debut of intracranial Hodgkin's lymphoma at diagnosis

La afectación intracraneal del linfoma de Hodgkin (LH) es extremadamente rara, especialmente como forma de presentación de la enfermedad. Muestra un patrón radiológico inespecífico, pudiendo ser confundido con otras entidades de mayor frecuencia y pronóstico radicalmente distinto. Anatomopatológicamente se caracteriza por la presencia de células grandes binucleadas (células de Reed-Sternberg) eIntracranial involvement in Hodgkin's lymphoma (HL) is extremely unusual, especially at the time of diagnosis. Because of its non-specific radiological behaviour, it can be confused with more common entities with a radically different prognosis. Pathologically, large and bi-nucleated cells, called Reed-Sternberg cells, embedded in an inflammatory network.

In this report we describe the clinical case of a patient, with no medical history, with left ocular pain and exophthalmos as presentation of intracranial HL at diagnosis and review the most current literature. Intracranial involvement is often associated with extracranial disease. Therefore, a systemic study including body computed tomography, bone marrow biopsy and ophthalmological evaluation is necessary. Intracranial lesions respond favourably to treatment and the prognosis depends on the extracranial involvement. To date, there is no standardised management scheme for these patients. For us, the primary role of surgery in this context is to perform a biopsy to confirm the histological diagnosis (AU)mbebidas en un entramado inflamatorio. Presentamos el caso de una paciente con dolor ocular y exoftalmos izquierdo como presentación clínica de afectación intracraneal por LH al diagnóstico de su enfermedad y revisamos la literatura más reciente al respecto. En pacientes con LH intracraneal es necesario realizar un estudio de extensión con tomografía computarizada corporal, biopsia de médula ósea y examen oftalmológico. Se asocia con gran frecuencia a enfermedad extracraneal, que marca el pronóstico. La lesión intracraneal presenta buena respuesta al tratamiento, que no sigue un esquema estandarizado. El papel de la cirugía es la realización de una biopsia para confirmar el diagnóstico (AU)

An optimized electro-fenton pretreatment for the degradation and mineralization of a mixture of ofloxacin, norfloxacin, and ciprofloxacin.

The electro-Fenton process (EFP) is a powerful advanced oxidation process beneficial to treating recalcitrant contaminants, and there has been a continuing interest in combining this technology to enhance the efficiency of conventional wastewater treatment processes. In this work, an optimized EFP process is performed as pretreatment for the degradation and mineralization of three blank fluoroquinolones (FQs) drugs: ofloxacin (OFL), norfloxacin (NOR), and ciprofloxacin (CIP). The optimization of the experiment was carried out using a Box-Behnken experimental design. Faster and complete degradation of the drugs mixture was achieved in 90 min with 61.12 ± 2.0% of mineralization in 180 min, under the optimized conditions: j = 244.0 mA cm-2, [Fe2+] = 0.31 mM, and [FQs] = 87.0 mg L-1. Furthermore, a low toxicity effluent was obtained in 90 min of the experiment, according to bioassay toxicity with Vibrio fischeri. Five short-chain carboxylic acids, including oxalic, maleic, oxamic, formic, and fumaric acids, were detected and quantified, in addition to F- and NO3- inorganic ions. The inhibition of the reactive oxygen species with scavenger proof was also evaluated in this paper.

Prospects of spectroscopic neutron imaging: optimizing experimental setups in battery electrolyte research.

Spectral neutron imaging methods provide valuable insights into the characterization of hydrogenous materials, including battery electrolytes. However, their application is constrained by sample geometry, setup parameters, and material chemistries, especially when studying physico-chemical changes in battery electrolytes. To address these limitations, we present a framework for simulating and optimizing the investigation of hydrogenous materials. Our approach combines quantitative modeling with experimental data to predict and optimize the contrast achievable in wavelength-resolved neutron imaging methods, thereby maximizing the information obtained in specific neutron imaging setups. While initially demonstrated at the BOA beamline of the Paul Scherrer Institute, this framework is applicable to any continuous source with spectral neutron imaging capabilities with a chopper disk. This work establishes a pathway for accurate studies of hydrogenous materials and their physico-chemical behavior, paving the way for advancements in the field of material characterization with wavelength-resolved neutron imaging.

Exophthalmos and ocular pain as clinical debut of intracranial Hodgkin's lymphoma at diagnosis.

Intracranial involvement in Hodgkin's Lymphoma (HL) is extremely unusual, especially at the time of diagnosis. Because of its non-specific radiological behaviour, it can be confused with more common entities with a radically different prognosis. Pathologically, large and bi-nucleated cells, called Reed-Sternberg cells, embedded in an inflammatory network. In this report we describe the clinical case of a patient, with no medical history, with left ocular pain and exophthalmos as presetation of intracranial HL at diagnosis and review the most current literature. Intracranial involvement is often associated with extracranial disease. Therefore, a systemic study including body computed tomography, bone marrow biopsy and ophthalmological evaluation is necessary. Intracranial lesions respond favourably to treatment and the prognosis depends on the extracranial involvement. To date, there is no standardised management scheme for these patients. For us, the primary role of surgery in this context is to perform a biopsy to confirm the histological diagnosis.

Hepatocellular carcinoma in Peru: A molecular description of an unconventional clinical presentation.

INTRODUCTION AND AIM: Hepatocellular carcinoma (HCC) is the third most frequent cancer of digestive tract tumors in Peru, with a high mortality rate of 17.7 per 100,000 inhabitants. A significant number of HCC cases in Peru do not follow the classic clinical epidemiology of the disease described in other parts of the world. Those patients present with a distinct transcriptome profile and a singular tumor process, suggesting a particular type of hepatocarcinogenesis in a portion of the Peruvian population. Our aim was to understand the clinical and biologic involvement of the epigenetic profile (methylation) and gene expression (transcriptome) of HCC in Peruvian patients. METHODS: HCC and liver transcriptome and DNA methylation profiles were evaluated in 74 Peruvian patients. RESULTS: When grouped by age, there was greater DNA methylation in younger patients with HCC but no differences with respect to the transcriptomic profile. A high prevalence of the hepatitis B virus (HBV) (>90%) was also observed in the younger patients with HCC. Enrichment analyses in both molecular profiles pinpointed PRC2 as an important molecular effector of that liver tumor process in Peruvian patients. CONCLUSION: HCC in Peruvian patients has a unique molecular profile, associated with the presence of HBV, as well as overall DNA hypermethylation related to undifferentiated liver cells or cellular reprogramming.

Endocarditis caused by Neisseria bacilliformis: a case report and review of literature.

A 58-years-old male with history of previous aortic prosthetic endocarditis caused by Enterococcus faecalis was admitted due to dyspnoea and fever. The two sets of blood cultures were positive for Neisseria bacilliformis. Transoesophageal echocardiography did not demonstrate endocarditis signs, but PET-CT scan showed active infection signs in the valvular aortic tube and possible infection in the aortic prosthetic valve. A six-week course of ampicillin was prescribed; gentamicin was added during the first two weeks. The patient continued a favourable clinical course. This is the 3rd described case of N. bacilliformis endocarditis and the first one in a prosthetic valve.

Kernohan-Woltman notch phenomenon: an exceptional neurological picture?

INTRODUCTION: Ipsilateral hemiparesis (IH) can be defined as a paradoxical dysfunction of the first motor neuron involving the extremities on the opposite side to that expected, given the location of the triggering intracranial pathology. Compression of the corticospinal tract (CSt) along its course through the contralateral cerebral peduncle against the free edge of the tentorium, known as the Kernohan-Woltman notch phenomenon (KWNP), represents the main cause of IH. METHODS: This retrospective study analyses a series of 12 patients diagnosed with IH secondary to KWNP treated at our institution, including a descriptive study of epidemiological, clinical, radiological, neurophysiological, and prognostic variables. RESULTS: In 75% of the cases, symptoms had an acute or subacute onset. Initial imaging studies showed signs of significant mass effect in half of the patients, whereas magnetic resonance imaging (MRI) identified a structural lesion in the contralateral cerebral peduncle in two thirds of them. Impairment of the motor evoked potentials (MEP) was verified in 4 patients. During follow-up 7 patients experienced improvement in motor activity, and near half of the cases were classified in the first three categories of the modified Rankin scale. CONCLUSIONS: In contrast to prior historical series, most of our patients developed a KWNP secondary to a traumatic mechanism. MRI represents the optimal method to identify both the classic cerebral peduncle notch and the underlying structural lesion of the CSt. The use of MEP can help to establish the diagnosis, especially in those cases lacking definite radiological findings.

An intrinsic temporal order of c-JUN N-terminal phosphorylation regulates its activity by orchestrating co-factor recruitment.

Protein phosphorylation is a major regulatory mechanism of cellular signalling. The c-JUN proto-oncoprotein is phosphorylated at four residues within its transactivation domain (TAD) by the JNK family kinases, but the functional significance of c-JUN multisite phosphorylation has remained elusive. Here we show that c-JUN phosphorylation by JNK exhibits defined temporal kinetics, with serine63 and serine73 being phosphorylated more rapidly than threonine91 and threonine93. We identify the positioning of the phosphorylation sites relative to the kinase docking motif, and their primary sequence, as the main factors controlling phosphorylation kinetics. Functional analysis reveals three c-JUN phosphorylation states: unphosphorylated c-JUN recruits the MBD3 repressor, serine63/73 doubly-phosphorylated c-JUN binds to the TCF4 co-activator, whereas the fully phosphorylated form disfavours TCF4 binding attenuating JNK signalling. Thus, c-JUN phosphorylation encodes multiple functional states that drive a complex signalling response from a single JNK input.