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Safety, tolerability, and immunogenicity of an aerosolised adenovirus type-5 vector-based COVID-19 vaccine (Ad5-nCoV) in adults: preliminary report of an open-label and randomised phase 1 clinical trial.

SARS-CoV-2 has caused millions of deaths, and, since Aug 11, 2020, 20 intramuscular COVID-19 vaccines have been approved for use. We aimed to evaluate the safety and immunogenicity of an aerosolised adenovirus type-5 vector-based COVID-19 vaccine (Ad5-nCoV) in adults without COVID-19 from China.

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Reactive Intralymphovascular Immunoblastic Proliferations Mimicking Aggressive Lymphomas.

Reactive intralymphovascular immunoblastic proliferations (ILVIPs) may mimic aggressive lymphomas and are rarely reported. Herein, we characterize the clinicopathologic features of 8 patients with ILVIPs. No patients had lymphadenopathy, hepatosplenomegaly, or other findings suggestive of lymphoma. The ILVIPs involved the small or large intestine (n=5) and appendix (n=3). Patients were evaluated for abdominal pain, suspected appendicitis, intestinal obstruction, diverticulitis, volvulus, or tumor resection. Histologic sections showed expanded lymphovascular spaces filled by intermediate to large immunoblasts, positive for CD38, CD43, CD45, CD79a, and MUM1/IRF4 in all cases tested. Five of 6 (83%) cases were positive for CD30. CD20 was weakly positive in a subset of cells in 2 (25%) cases, and PAX5 was weakly positive in 4 (50%) cases. The immunoblasts expressed polytypic light chains in all cases tested. In 1 case, a subset of immunoblasts expressed T-cell markers indicating the presence of a T-cell component. The immunoblasts were negative for ALK, BCL-2, BCL-6, CD10, CD56, CD138, and Epstein-Barr virus-encoded small RNA in all cases assessed. The proliferation index shown by Ki-67 was high with a median of 80%. In all 6 cases tested, the immunoblasts were shown within lymphatic channels highlighted by D2-40. In conclusion, ILVIPs can be rarely observed in patients with inflammatory or infectious conditions, especially in gastrointestinal tract surgical specimens. The immunoblasts are predominantly of B-lineage with a postgerminal center immunophenotype and are located within lymphatic channels. It is essential to distinguish reactive ILVIPs from aggressive lymphomas to avoid unnecessary therapy.

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Safety of autologous bone marrow-derived mesenchymal stem cells in erectile dysfunction: an open-label phase 1 clinical trial.

The efficacy of phosphodiesterase type 5 inhibitors (PDE5Is), which are commonly used to treat erectile dysfunction (ED), is not satisfactory in patients with denervation of the cavernous nerve due to pelvic surgeries and diabetes mellitus (DM). Pre-clinical studies using bone marrow-derived mesenchymal stem cells (BMSCs) to treat ED have shown promising results. The authors conducted a phase 1 clinical trial with autologous BMSCs in patients with ED due to radical prostatectomy or DM.

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Neuroinvasive disease due to West Nile virus: clinical and imaging findings associated with a re-emerging pathogen.

The West Nile virus (WNV) is an arbovirus than can infect human beings and cause severe neuroinvasive disease. Taking the outbreak that occurred in Spain in 2020 as a reference, this article reviews the clinical and imaging findings for neuroinvasive disease due to WNV. We collected demographic, clinical, laboratory, and imaging (CT and MRI) variables for 30 patients with WNV infection diagnosed at our center. The main clinical findings were fever, headache, and altered levels of consciousness. Neuroimaging studies, especially MRI, are very useful in the diagnosis and follow-up of these patients. The most common imaging findings were foci of increased signal intensity in the thalamus and brainstem in T2-weighted sequences; we illustrate these findings in cases from our hospital.

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What is the link between migraine and psychiatric disorders? From epidemiology to therapeutics.

The association between migraine and psychiatric disorders is well documented through numerous population-based studies. The results of these studies are coherent and show an increased risk of suffering from depression, bipolar disorders, numerous anxiety disorders, especially post-traumatic stress disorder. This raises the question of stress as a precipitating factor for migraine illness. Psychiatric comorbidity is even more frequent in chronic migraine than in episodic migraine patients. Many prospective studies have shown that psychiatric comorbidity could be considered as a risk factor for migraine chronicization. Psychiatric comorbidity is also responsible for an increase of the frequency of anti-migraine drug intake, a worsening of quality of life and a worsening of functional impairment. It is also responsible for an increase in the direct and indirect costs of migraine. The reason why psychiatric comorbidity is so high in migraineurs is not unambiguous. Multiple causal relationships and common etiological factors are linked. Recently, genome-wide association studies gave leads to a genetic common heritability between major depressive disorder and migraine. For clinicians, an important topic remains how to treat migraineurs with psychiatric comorbidity. These patients suffer frequently from severe migraine or refractory migraine. Antidepressant and anti-convulsive drugs can be useful, as well as psychological therapies. But moreover, it is of utmost importance to propose an integrated multidisciplinary approach to these difficult patients.

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Perioperative medicine role in painful knee prosthesis prevention.

Total knee arthroplasty is one of the most frequently performed orthopaedic surgeries. However, up to 20% of patients develop persistent postoperative pain. Persistent postoperative pain may be an extension of acute postoperative pain, but can also occur after more than 3 months without symptoms. Risk factors associated with persistent postoperative pain after arthroplasty have now been characterised within the patient's perioperative context (preoperative, intraoperative and postoperative), and can be grouped under genetic, demographic, clinical, surgical, analgesic, inflammatory and psychological factors. Identification and prevention of persistent postoperative pain through a multimodal and biopsychosocial approach is essential in the context of perioperative medicine, and has been shown to prevent or ameliorate postoperative pain.

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The effect of erector spinae plane block on postoperative analgesia and respiratory function in patients undergoing laparoscopic cholecystectomy: A double-blind randomized controlled trial.

Laparoscopic cholecystectomy (LC) causes moderate-to-severe postoperative pain. Postoperative pain is one of the leading contributors to respiratory dysfunction following surgery. This study investigated the effect of erector spinae plane (ESP) block on postoperative analgesia and respiratory function in patients undergoing LC.

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Pain and spastic features in chronic DOC patient: A cross-sectional retrospective study.

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Intraneural fibrosis and loss of microvascular architecture – Key findings investigating failed human nerve allografts.

Processed nerve allografts are increasingly used in clinical nerve reconstruction with promising results. However, allograft failure has been reported, leading to chronic pain and persistent loss of function. In the present work, we performed a histological and immunohistochemical analysis of two failed allograft reconstructions of a sensory human nerve one year after primary surgery.

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Prolonged anesthesia and decreased toxicity of enantiomeric-excess Bupivacaine loaded in Ionic gradient liposomes.

Bupivacaine is the most employed local anesthetic in surgical procedures, worldwide. Its systemic toxicity has directed the synthesis of the less toxic, S(-) enantiomer. This work describes a formulation of ionic gradient liposomes (IGL) containing BVC, an enantiomeric excess mixture of 75% S(-) and 25% R(+) bupivacaine. IGL prepared with 250 mM (NH)SO in the inner aqueous core of phosphatidylcholine and cholesterol (3:2 mol%) vesicles plus 0.5% BVC showed average sizes of 312.5 ± 4.5 nm, low polydispersity (PDI < 0.18), negative zeta potentials (- 14.2 ± 0.2 mV) and were stable for 360 days. The encapsulation efficiency achieved with IGL (%EE = 38.6%) was higher than with IGL prepared with racemic bupivacaine (IGL, %EE = 28.3%). TEM images revealed spherical vesicles and µDSC analysis provided evidence on the interaction of the anesthetic with the lipid bilayer. Then, in vitro – release kinetics and cytotoxicity- and in vivo – toxic effects in Zebrafish and biochemical/histopathological analysis plus analgesia in Wistar rats – tests were performed. IGL exhibited negligible toxicity against Schwann cells and Zebrafish larvae, and it did not affect biochemical markers or the morphology of rat tissues (heart, brain, cerebellum, sciatic nerve). The in vitro release of BVC from IGL was extended from 4 to 24 h, justifying the prolonged anesthetic effect measured in rats (∼ 9 h). The advantages of IGL formulation over IGL and plain bupivacaine formulations (prolonged anesthesia, preferential sensorial blockade, and no toxicity) confirm its potential for clinical use in surgical anesthesia.

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