Lateral Femoral Cutaneous Nerve Block or Wound Infiltration Combined with Pericapsular Nerve Group (PENG) Block for Postoperative Analgesia following Total Hip Arthroplasty through Posterior Approach: A Randomized Controlled Trial.

Background: Pericapsular nerve group (PENG) block, although effective for pain management following total hip arthroplasty (THA), does not cover skin analgesia. In this randomized controlled trial, we compared the effectiveness of PENG block combined with lateral femoral cutaneous nerve (LFCN) block or wound infiltration (WI) on postoperative analgesia and functional outcomes. Methods: Fifty patients undergoing posterior-approached THA under spinal anesthesia were randomly allocated to receive LFCN block with 10 mL of 0.5% ropivacaine or WI with 20 mL of 0.5% ropivacaine. In both groups, PENG block was performed by injecting 20 mL of 0.5% ropivacaine. Primary outcomes were static and dynamic pain scores (0-10 numeric rating scale) measured in the first 24 h after surgery. Secondary outcomes included postoperative opioid consumption, functional assessment and length of hospital stay. Results: Postoperative static NRS of patients receiving LFCN was higher than that of patients receiving WI at 6 h but lower at 24 h, with a median (IQR) of 3 (2-4) vs. 2 (1-2) (p < 0.001) and 2 (2-3) vs. 3 (3-4) (p = 0.02), respectively. Static pain scores at 12 h did not show significant differences, with an NRS of 3 (2-4) for WI vs. 3 (3-4) for LFCN (p = 0.94). Dynamic pain and range of movement followed a similar trend. No significant differences were detected in other outcomes. Conclusions: LFCN block was not inferior to WI for postoperative analgesia and functional recovery in association with PENG block during the first postoperative day, although it had worse short-term pain scores. Based on these results, it is reasonable to consider LFCN block as a valid alternative to WI or even a complementary technique added to WI to enhance skin analgesia during the first 24 h after THA. Future studies are expected to confirm this hypothesis and find the best combination between PENG block and other techniques to enhance analgesia after THA.

A Pharmacovigilance Study on the Safety of Axicabtagene Ciloleucel Based on Spontaneous Reports from the EudraVigilance Database.

During pre-approval clinical trials, the safety of axi-cel, a second-generation CAR-T-cell therapy directed against CD19, which dramatically improved the prognosis of intractable B-cell lymphomas, has been investigated only in about 400 patients. Therefore, additional information on this issue is urgently needed. In the present paper, we evaluated the 2905 ICSRs with axi-cel as the suspected drug that had been uploaded in the EudraVigilance database from 1 January 2018 to 31 December 2022. About 80% of the reported adverse events were serious, and about 20% of them did not fully resolve or caused death. The adverse events most-frequently reported were Nervous system disorders (25.6%) and, among them, immune-effector-cell-associated neurotoxicity syndrome, followed by Immune system disorders (23.1%), General disorders and administration site conditions (12.0%), Blood and lymphatic system disorders (7.2%), and Infections and infestations (5.8%). Disproportionality analysis showed that the frequency of reported adverse events related to the nervous system was higher with axi-cel than with the other approved CAR-T-cells, except brexu-cel. In conclusion, real-world pharmacovigilance data showed that nervous system and immune system disorders are the adverse events most reported in axi-cel-related ICSRs and suggest that axi-cel could be more neurotoxic than other CAR-T-cells.

The Impact of Non-Andrological Medications on Semen Characteristics, Oxidative Stress and Inflammatory Parameters.

Background and Objectives: The aim of this study was to evaluate the impact of medications on oxidative stress, inflammatory biomarkers and semen characteristics in males with idiopathic infertility. Materials and Methods: In this observational case-control clinical study, 50 men with idiopathic infertility were enrolled, of whom 38 (the study group) were on pharmacological treatment and 12 made up the control group. The study group was clustered according to the medications (Group A: anti-hypertensive, n = 10; Group B: thyroxine, n = 6; Group C: non-steroidal anti-inflammatory drugs, n = 13; Group D: miscellaneous, n = 6; Group E: lipid-lowering drugs, n = 4). Semen analyses were performed according to WHO 2010 guidelines. Interleukins (IL)-10, IL-1 beta, IL-4, IL-6, Tumor Necrosis Factor- alpha (TNF-alpha) and IL-1 alpha were determined using a solid-phase sandwich immunoassay. The diacron reactive oxygen metabolites, d-ROMs test, was performed by means of a colorimetric determination of reactive oxygen metabolites and measured with a spectrophotometer. Beta-2-microglobulin and cystatin-C were measured with an immunoturbidimetric analyzer. Results: No differences between the study and control groups for age and macroscopic and microscopic semen characteristics were found, nor were any differences found after clustering according to the drug categories. IL-1 alpha and IL-10 were significantly lower in the study group compared with the control group; IL-10 was significantly lower in groups A, B, C and D compared with the control group. Furthermore, a direct correlation between IL-1 alpha, IL-10 and TNF-alpha and leukocytes was found. Conclusions: Despite the sample size limitations, the data suggest a correlation between drug use and activation of the inflammatory response. This could clarify the pathogenic mechanism of action for several pharmacological classes on male infertility.

The Safety Profile of General and Local Anaesthetic Agents: Data Collected during 20 Years of Spontaneous Reporting Activities in the Campania Region (Southern Italy).

BACKGROUND: General and local anaesthetics are widely used during surgery. These drugs have peculiar safety profiles, being commonly associated with mild and reversible local adverse drug reactions (ADRs), but also with more severe and systemic ADRs, including respiratory and cardiovascular depression and anaphylaxis. METHODS AND OBJECTIVES: We carried out a descriptive analysis of Individual Case Safety Reports (ICSRs) sent to the Campania Regional Centre of Pharmacovigilance (Southern Italy) from 2001 to 2021 that reported general or local anaesthetics as suspected drugs, with the aim of describing their overall characteristics, focussing on the ADRs' seriousness and distribution by System Organ Class (SOC) and Preferred Term (PT). RESULTS: A total of 110 ICSRs documenting general or local anaesthetics were sent to the Italian pharmacovigilance database during 20 years of spontaneous reporting activities in the Campania region. ADRs mainly occurred in patients with a median age of 48 years and in a slightly higher percentage of men. ADRs were more commonly classified as not serious and had a favourable outcome. In terms of ADRs' distribution by SOC and PT, both general and local anaesthetics were associated with general and cutaneous disorders, with common ADRs that included lack of efficacy, rash, and erythema. In addition, general anaesthetics were associated with the occurrence of respiratory ADRs, while local anaesthetics were associated with the occurrence of nervous ADRs. CONCLUSION: Even though a limited number of ICSRs documenting anaesthetics-induced ADRs were retrieved from the Italian spontaneous reporting database in the Campania region, we believe that the continuous monitoring of these drugs is highly recommended, especially among the frail population.

The Glioblastoma Microenvironment: Morphology, Metabolism, and Molecular Signature of Glial Dynamics to Discover Metabolic Rewiring Sequence.

Different functional states determine glioblastoma (GBM) heterogeneity. Brain cancer cells coexist with the glial cells in a functional syncytium based on a continuous metabolic rewiring. However, standard glioma therapies do not account for the effects of the glial cells within the tumor microenvironment. This may be a possible reason for the lack of improvements in patients with high-grade gliomas therapies. Cell metabolism and bioenergetic fitness depend on the availability of nutrients and interactions in the microenvironment. It is strictly related to the cell location in the tumor mass, proximity to blood vessels, biochemical gradients, and tumor evolution, underlying the influence of the context and the timeline in anti-tumor therapeutic approaches. Besides the cancer metabolic strategies, here we review the modifications found in the GBM-associated glia, focusing on morphological, molecular, and metabolic features. We propose to analyze the GBM metabolic rewiring processes from a systems biology perspective. We aim at defining the crosstalk between GBM and the glial cells as modules. The complex networking may be expressed by metabolic modules corresponding to the GBM growth and spreading phases. Variation in the oxidative phosphorylation (OXPHOS) rate and regulation appears to be the most important part of the metabolic and functional heterogeneity, correlating with glycolysis and response to hypoxia. Integrated metabolic modules along with molecular and morphological features could allow the identification of key factors for controlling the GBM-stroma metabolism in multi-targeted, time-dependent therapies.

Influence of different lipid emulsions on specific immune cell functions in head and neck cancer patients receiving supplemental parenteral nutrition: An exploratory analysis.

OBJECTIVES: The effect of diet on immune responses is an area of intense investigation. Dietary lipids have been shown to differently influence and fine-tune the reactivity of immune cell subsets, thus potentially affecting clinical outcomes. Patients with head and neck squamous cell carcinoma face malnutrition, due to swallowing impairment related to the tumor site or to treatment sequalae, and may need supplemental parenteral nutrition (SPN) in addition to oral feeding when enteral nutrition is not feasible. Additionally, immune depression is a well-known complication in these patients. Parenteral nutrition (PN) bags contain amino acids, minerals, electrolytes and mostly lipids that provide calories in a concentrated form and are enriched with essential fatty acids. The aim of this study was to investigate multiple parameters of the immune responses in a cohort of patients with head and neck squamous cell carcinoma undergoing supplemental PN with bags enriched in ω-3 or ω-9 and ω-6 fatty acids. METHODS: To our knowledge, this was the first exploratory study to investigate the effects of two different PN lipid emulsions on specific immune cells function of patients with advanced head and neck squamous carcinoma. ω-3-enriched fish-oil-based- and ω-6- and ω-9-enriched olive-oil-basedSPN was administered to two groups of patients for 1 wk in the context of an observational multicentric study. Polychromatic flow cytometry was used to investigate multiple subsets of leukocytes, with a special focus on cellular populations endowed with antitumor activity. RESULTS: Patients treated with olive-oil-based PN showed an increase in the function of the innate (natural killer cells and monocytes) and adaptive (both CD4 and CD8 cells) arms of the immune response. CONCLUSION: An increase in the function of the innate and adaptive arms of the immune response may favor antitumoral responses.

Epidural Steroid Injections for Low Back Pain: A Narrative Review.

Low back pain represents a significant socioeconomic burden. Several nonsurgical medical treatments have been proposed for the treatment of this disabling condition. Epidural steroid injections (ESIs) are commonly used to treat lumbosacral radicular pain and to avoid surgery. Even though it is still not clear which type of conservative intervention is superior, several studies have proved that ESIs are able to increase patients' quality of life, relieve lumbosacral radicular pain and finally, reduce or delay more invasive interventions, such as spinal surgery. The aim of this narrative review is to analyze the mechanism of action of ESIs in patients affected by low back pain and investigate their current application in treating this widespread pathology.

EBV-specific CD8 T lymphocytes and B cells during glatiramer acetate therapy in patients with MS.

OBJECTIVE: Infection with Epstein-Barr virus (EBV) has been associated with clinical activity and risk of developing MS. The purpose of this study is to investigate the impact of glatiramer acetate (GA) therapy on EBV-specific immune responses and disease course. METHODS: We characterized EBV-specific CD8 T lymphocytes and B cells during disease-modifying treatments in 2 groups of patients with MS. We designed a 2-pronged approach consisting of a cross-sectional study (39 untreated patients, 38 patients who had undergone 12 months of GA treatment, and 48 healthy donors compatible for age and sex with the patients with MS) and a 12-month longitudinal study (35 patients treated with GA). CD8 EBV-specific T cells and B lymphocytes were studied using pentamers and multiparametric flow cytometry. RESULTS: We find that treatment with GA enhances viral recognition by inducing an increased number of circulating virus-specific CD8 T cells (p = 0.0043) and by relieving their features of exhaustion (p = 0.0053) and senescence (p < 0.0001, p = 0.0001). B cells, phenotypically and numerically tracked along the 1-year follow-up study, show a steady decrease in memory B-cell frequencies (p = 0.025), paralleled by an increase of the naive B subset. CONCLUSION: GA therapy acts as a disease-modifying therapy restoring homeostasis in the immune system, including anti-EBV responses.

A Leukemia-Associated CD34/CD123/CD25/CD99+ Immunophenotype Identifies FLT3-Mutated Clones in Acute Myeloid Leukemia.

PURPOSE: We evaluated leukemia-associated immunophenotypes (LAIP) and their correlation with fms-like tyrosine kinase 3 (FLT3) and nucleophosmin (NPM1) gene mutational status in order to contribute a better identification of patients at highest risk of relapse in acute myeloid leukemia (AML). EXPERIMENTAL DESIGN: Bone marrow samples from 132 patients with AML were analyzed by nine-color multiparametric flow cytometry. We confirmed the presence of the mutation in diagnostic samples and in sorted cells by conventional RT-PCR and by patient-specific RQ-PCR. RESULTS: Within the CD34(+) cell fraction, we identified a discrete population expressing high levels of the IL3 receptor α-chain (CD123) and MIC-2 (CD99) in combination with the IL2 receptor α-chain (CD25). The presence of this population positively correlated with the internal tandem duplications (ITD) mutation in the FLT3 gene (r = 0.71). Receiver operating characteristics showed that, within the CD34(+) cell fraction a percentage of CD123/CD99/CD25(+) cells ≥11.7% predicted FLT3-ITD mutations with a specificity and sensitivity of >90%. CD34/CD123/CD99/CD25(+) clones were also detectable at presentation in 3 patients with FLT3 wild-type/NPM1(+) AML who relapsed with FLT3-ITD/NPM1(+) AML. Quantitative real-time PCR designed at relapse for each FLT3-ITD in these three cases confirmed the presence of low copy numbers of the mutation in diagnostic samples. CONCLUSIONS: Our results suggest that the CD34/CD25/CD123/CD99(+) LAIP is strictly associated with FLT3-ITD-positive cells.