Changes in hospital admissions for facial fractures during and after COVID 19 pandemic: national multicentric epidemiological analysis on 2938 patients.

PURPOSE: The objective of this multicenter study was to examine the differences in maxillo-facial fractures epidemiology across the various phases of the SARS-CoV-2 pandemic. METHODS: This is a retrospective study on patients who underwent surgery for facial bone fractures in 18 maxillo-facial surgery departments in Italy, spanning from June 23, 2019, to February 23, 2022. Based on the admission date, the data were classified into four chronological periods reflecting distinct periods of restrictions in Italy: pre-pandemic, first wave, partial restrictions, and post-pandemic. Epidemiological differences across the groups were analysed. RESULTS: The study included 2938 patients. A statistically significant difference in hospitalization causes was detected between the pre-pandemic and first wave groups (p = 0.005) and between the pre-pandemic and partial restriction groups (p = 0.002). The differences between the pre- and post-pandemic groups were instead not significant (p = 0.106). Compared to the pre-pandemic period, the number of patients of African origin was significantly higher during the first wave and the post-pandemic period. No statistically significant differences were found across the periods concerning gender, age, fracture type, treatment approach, and hospital stay duration CONCLUSIONS: The COVID-19 pandemic brought about significant changes in fracture epidemiology, influenced by the restrictive measures enforced by the government in Italy. Upon the pandemic's conclusion, the fracture epidemiology returned to the patterns observed in the pre-pandemic period.

Powerful anti-inflammatory action of luteolin: Potential increase with IL-38.

Luteolin belongs to the flavone family originally present in some fruits and vegetables, including olives, which decrease intracellular levels of reactive oxygen species (ROS) following the activation of various stimuli. Luteolin inhibits inflammation, a complex process involving immune cells that accumulate at the site of infectious or non-infectious injury, with alteration of the endothelium leading to recruitment of leukocytes. Cytokines have been widely reported to act as immune system mediators, and IL-1 family members evolved to assist in host defense against infections. Interleukin (IL)-1 and Toll-like receptor (TLR) are involved in the innate immunity in almost all living organisms. After being synthesized, IL-1 induces numerous inflammatory mediators including itself, other pro-inflammatory cytokines/chemokines, and arachidonic acid products, which contribute to the pathogenesis of immune diseases. Among the 11 members of the IL-1 family, there are two new cytokines that suppress inflammation, IL-37 and IL-38. IL-38 binds IL-36 receptor (IL-1R6) and inhibits several pro-inflammatory cytokines, including IL-6, through c-Jun N-terminal kinase (JNK) induction and reducing AP1 and nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) activity, alleviating inflammatory diseases. Therefore, since luteolin, IL-37 and IL-38 are all anti-inflammatory molecules with different signaling pathways, it is pertinent to recommend the combination of luteolin with these anti-inflammatory cytokines in inflammation.

Endoscopic Transorbital Approaches to Anterior and Middle Cranial Fossa: Exploring the Potentialities of a Modified Lateral Retrocanthal Approach.

BACKGROUND: Among the new perspectives to revolutionize skull base surgery, there are the transorbital neuroendoscopic (TONES) approaches to reach the anterior and middle cranial fossa (ACF and MCF). We conceived to explore the potentialities of a modified superiorly and medially extended lateral retrocanthal (LRC) approach. METHODS: Six head specimens were dissected. Applying the established conic model and the key surgical landmark of sphenofrontal suture, we tested the feasibility of a modified LRC to reach ACF and MCF; computed tomography (CT) scans were performed before and after dissection to obtain a morphometric analysis of the surgical corridors using a polygonal surfaces model. RESULTS: Through our anatomical study, we were able to identify and explore 3 different surgical corridors to reach the ACF and MCF: the superomedial, the superolateral, and the inferolateral. The superomedial corridor appeared most suitable to reach the medial part of the ACF and the optic-carotid region, whereas through the superolateral and inferolateral corridors it was possible to reach and explore the lateral part of ACF and MCF. The mean volumes of the 3 surgical corridors calculated on post-dissection CT scans were: 12.72 ± 1.99, 5.69 ± 0.34, and 6.24 ± 0.47 cm3, respectively. CONCLUSIONS: The development of TONES approaches has not replaced the traditional open or endoscopic approach; nonetheless, identification of surgical corridors and the possibility to combine them represent a major breakthrough. Clinical studies are necessary to demonstrate their validity and test the effectiveness, safety, and reproducibility of TONES approaches in managing lesions harboring in the ACF and MCF.

Advances in Mast Cell Activation by IL-1 and IL-33 in Sjögren's Syndrome: Promising Inhibitory Effect of IL-37.

Sjögren's syndrome (SS) is a chronic autoimmune inflammatory disease that affects primarily older women and is characterized by irreversible damage of the exocrine glands, including tear (xerophthalmia) and salivary glands (xerostomia). Secretory glands lose their functionality due to the infiltration of immune cells, which produce cytokines and cause inflammation. Primary SS is characterized by dry syndrome with or without systemic commitment in the absence of other pathologies. Secondary SS is accompanied by other autoimmune diseases with high activation of B lymphocytes and the production of autoantibodies, including the rheumatoid factor. Other cells, such as CD4+ T cells and mast cells (MCs), participate in SS inflammation. MCs are ubiquitous, but are primarily located close to blood vessels and nerves and can be activated early in autoimmune diseases to express a wide variety of cytokines and chemokines. In the SS acute phase, MCs react by generating chemical mediators of inflammation, tumor necrosis factor (TNF), and other pro-inflammatory cytokines such as interleukin (IL)-1 and IL-33. IL-33 is the specific ligand for ST2 capable of inducing some adaptive immunity TH2 cytokines but also has pro-inflammatory properties. IL-33 causes impressive pathological changes and inflammatory cell infiltration. IL-1 family members can have paracrine and autocrine effects by exacerbating autoimmune inflammation. IL-37 is an IL-1 family cytokine that binds IL-18Rα receptor and/or Toll-like Receptor (TLR)4, exerting an anti-inflammatory action. IL-37 is a natural inhibitor of innate and acquired immunity, and the level is abnormal in patients with autoimmune disorders. After TLR ligand activation, IL-37 mRNA is generated in the cytoplasm, with the production of pro-IL-37 and later mature IL-37 caspase-1 mediated; both precursor and mature IL-37 are biologically active. Here, we discuss, for the first time, the current knowledge of IL-37 in autoimmune disease SS and propose a new therapeutic role.

New aspect of allergic contact dermatitis, an inflammatory skin disorder mediated by mast cells: Can IL-38 help?

Atopic dermatitis (AD) is an inflammatory reaction of the skin that can occur in several parts of the body and can be provoked or exacerbated by food and/or environmental compounds. Allergic contact dermatitis (ACD) is a potential enhancer of AD, and an epidermal barrier breaker which induces greater penetration of allergens and other compounds. ACD presents an eczematous rash, red and itchy, with inflammation mediated by cytokines. ACD is an immunological disorder caused by contact with an allergic substance (haptens) that involves immunotoxicity, irritation and inflammation. Mast cells (MCs) are important immune cells that intervene, as effector cells, in allergic and anaphylactic reactions, asthma, autoimmune diseases and cancer. In dermatitis, activated MCs release inflammatory chemical mediators and secrete pro-inflammatory cytokines, including interleukin (IL)-1, TNF, and IL-33. In addition, IL-1 activates MCs to generate a number of cytokines and chemokines, which aggravate inflammation. IL-38 cytokine, an IL-1 family member, is secreted by activated immune cells, including macrophages and lymphocytes, and possesses anti-inflammatory activity. IL-38, by binding IL-36 receptor (IL-36R), provokes suppression of inflammation in many immune diseases. In particular, IL-38 inhibits the generation of IL-1, IL-6 and IL-8 along with other cytokines/chemokines. Here, we hypothesize for the first time that IL-38 may suppresses the inflammatory response in dermatitis, exerting beneficial therapeutic effect.

Mast Cells Mediate Rheumatoid Arthritis-Inhibitory Role of IL-37.

Rheumatoid arthritis (RA) is an autoimmune, chronic inflammatory, disabling arthropathy that severely affects the quality of life. This disease involves several proinflammatory cytokines, including interleukin (IL)-1ß and tumor necrosis factor (TNF). IL-1 induces TNF and vice versa, causing joint damage and cartilage degradation. Current antirheumatic drugs may be effective, but they possess many unwanted side effects. In recent years, inhibitors of proinflammatory cytokines have increasingly entered mainstream clinical practice. Recent evidence indicates that IL-37, which has anti-inflammatory properties, is increased in the serum and is released from white blood cells in patients with RA. Mast cells (MCs), stimulated by the neuropeptide substance P (SP) and IL-33, release IL-1ß and TNF. Recent evidence indicates that large amounts of IL-1ß and TNF can be released from human MCs, which also secrete CXCL8, which promotes migration of immune cells, causing erosion of the bone and cartilage. Treatment with IL-37 can block the MC stimulation and release of inflammatory compounds, attenuating the severity of the disease and/or altering its progression.

Vertebral artery loop--a cause of cervical radiculopathy.

OBJECTIVE: To report a case of cervical radiculopathy caused by an anomalous vertebral artery (VA) and illustrate the efficacy of microvascular decompression by the anterolateral approach. METHODS: A 50-year-old woman was referred because of an 8-year history of progressive left C6 radiculopathy refractory to other forms of treatment, including C5-6 anterior cervical discectomy. Clinical and radiologic evaluation showed an abnormally tortuous loop of V2 causing direct neurovascular compression. RESULTS: A left cervical anterolateral approach was used to expose the anomalous loop. After a generous bony decompression, the loop was identified, and the artery was mobilized and ultimately separated from the C6 nerve root removing the direct pulsatile compression. CONCLUSIONS: Cervical root compression by an aberrant or anomalous extracranial VA is a rare cause of radiculopathy. The best management of such lesions is the anterolateral approach with bony and direct microvascular decompression.

Decompressive craniectomy and early cranioplasty for the management of severe head injury: a prospective multicenter study on 147 patients.

OBJECTIVE: In emergency care of patients with severe blunt head injury, uncontrollable high intracranial pressure is one of major causes of morbidity and mortality. The purpose of this study was to evaluate the efficacy of aggressive surgical treatment in managing uncontrollable elevated intracranial pressure coupled with early skull reconstruction. METHODS: This was a prospective study on a series of 147 consecutive patients, managed according to the same protocol by five different neurosurgical units, for severe head injuries (Glasgow coma scale score ≤8/15 and high intracranial pressure >25 mm Hg) during a five-year period. All patients received a wide decompressive craniectomy and duroplasty in the acute phase, and a cranioplasty was also performed within 12 weeks (median 6 weeks, range 4-12 weeks). RESULTS: The emergency decompressive surgery was performed within 28 hours (median 16 hours, range 6-28 hours) after sustaining the head injury. The median preoperative Glasgow coma scale score was 6/15 (range 3-8/15). At a mean follow-up of 26 months (range 14-74 months) 14 patients were lost to long-term follow-up, leaving only 133 patients available for the study. The outcome was favorable in 89 (67%, Glasgow outcome score 4 or 5), it was not favorable in 25 (19%, Glasgow outcome score 2 and 3), and 19 patients (14%) died. A younger age (<50 years) and earlier operation (within 9 hours from trauma) had a significant effect on positive outcomes (P < 0.0001 and P < 0.03, respectively). CONCLUSIONS: A prompt aggressive surgery, including a wide decompressive craniectomy coupled with early cranioplasty, could be an effective treatment method to improve the outcome after a severe closed head injury reducing, perhaps, many of the complications related to decompressive craniectomy.