Low dose aspirin and clinical outcomes in patients with SARS-CoV-2 pneumonia: a propensity score-matched cohort analysis from the National SIMI­COVID­19 Registry.

BACKGROUND: SARS- CoV-2 virus has had dramatic consequences worldwide being able to cause acute respiratory distress syndrome (ARDS), massive thrombosis and pulmonary embolism and, finally, patients' death. In COVID-19 infection, platelets have a procoagulant phenotype that can cause thrombosis in the pulmonary and systemic vascular network. Aspirin is a well-known anti-platelet drug widely used for the prevention of cardiovascular events and systematic reviews suggest a possible benefit of low-dose aspirin (LDA) use in the prevention and treatment of ARDS in patients with COVID-19 infection. However, several studies are available in the literature which do not support any benefits and no association with the patients' outcome. Therefore, currently available data are inconclusive. MATERIALS AND PATIENTS: Data from the nationwide cohort multicenter study of the Italian Society of Internal Medicine (SIMI) were analyzed. We conducted a propensity score-matched cohort analysis to investigate the impact of chronic assumption of LDA on mortality of adult COVID-19 patients admitted in Internal Medicine Units (IMU). Data from 3044 COVID-19 patients who referred to 41 Italian hospitals between February 3rd to May 8th 2020 were analyzed. A propensity score-matched analysis was conducted using the following variables: age, sex, hypertension, hyperlipidemia diabetes, atrial fibrillation, cerebrovascular disease, COPD, CKD and stratified upon LDA usage, excluding anticoagulant treatment. After matching, 380 patients were included in the final analysis (190 in LDA group and 190 in no-LDA group). RESULTS: 66.2% were male, median age was 77 [70-83]. 34.8% of the population died during the hospitalization. Cardiovascular diseases were not significantly different between the groups. After comparison of LDA and no-LDA subgroups, we didn't record a significant difference in mortality rate (35.7% vs 33.7%) duration of hospital stay and ICU admission. In a logistic regression model, age (OR 1.05; 95% CI 1.01-1.09), FiO2 (OR 1.024; 95% CI 1.03-1.04) and days between symptoms onset and hospitalization (OR 0.93; 95% CI 0.87-0.99) were the only variables independently associated with death.

Utilization of multiparametric prostate magnetic resonance imaging in clinical practice and focal therapy: report from a Delphi consensus project.

PURPOSE: To codify the use of multiparametric magnetic resonance imaging (mpMRI) for the interrogation of prostate neoplasia (PCa) in clinical practice and focal therapy (FT). METHODS: An international collaborative consensus project was undertaken using the Delphi method among experts in the field of PCa. An online questionnaire was presented in three consecutive rounds and modified each round based on the comments provided by the experts. Subsequently, a face-to-face meeting was held to discuss and finalize the consensus results. RESULTS: mpMRI should be performed in patients with prior negative biopsies if clinical suspicion remains, but not instead of the PSA test, nor as a stand-alone diagnostic tool or mpMRI-targeted biopsies only. It is not recommended to use a 1.5 Tesla MRI scanner without an endorectal or pelvic phased-array coil. mpMRI should be performed following standard biopsy-based PCa diagnosis in both the planning and follow-up of FT. If a lesion is seen, MRI-TRUS fusion biopsies should be performed for FT planning. Systematic biopsies are still required for FT planning in biopsy-naïve patients and for patients with residual PCa after FT. Standard repeat biopsies should be taken during the follow-up of FT. The final decision to perform FT should be based on histopathology. However, these consensus statements may differ for expert centers versus non-expert centers. CONCLUSIONS: The mpMRI is an important tool for characterizing and targeting PCa in clinical practice and FT. Standardization of acquisition and reading should be the main priority to guarantee consistent mpMRI quality throughout the urological community.

Oxysterols and redox signaling in the pathogenesis of non-alcoholic fatty liver disease.

Oxysterols are oxidized species of cholesterol coming from exogenous (e.g. dietary) and endogenous (in vivo) sources. They play critical roles in normal physiologic functions such as regulation of cellular cholesterol homeostasis. Most of biological effects are mediated by interaction with nuclear receptor LXRα, highly expressed in the liver as well as in many other tissues. Such interaction participates in the regulation of whole-body cholesterol metabolism, by acting as "lipid sensors". Moreover, it seems that oxysterols are also suspected to play key roles in several pathologies, including cardiovascular and inflammatory disease, cancer, and neurodegeneration. Growing evidence suggests that oxysterols may contribute to liver injury in non-alcoholic fatty liver disease. The present review focuses on the current status of knowledge on oxysterols' biological role, with an emphasis on LXR signaling and oxysterols' physiopathological relevance in NAFLD, suggesting new pharmacological development that needs to be addressed in the near future.

Anaphylactic shock during hyperbaric oxygen therapy.

A case of a 38-year-old woman is reported who was treated with hyperbaric oxygen therapy to cure a dehiscent wound. She suffered from "oral-allergy syndrome" (OAS) while eating certain fruits, and from itching when wearing latex gloves to handle hair dyes. Fifteen minutes after the start of compression, malaise, anxiety, dyspnoea, tachycardia, cold sweating and laryngeal stridor occurred. Despite intensive care treatment, face angioedema persisted for several days. On the basis of history, radioallergosorbent test (RAST) and prick tests, latex was assumed to be responsible for the anaphylactic reaction. To our knowledge, this is the first extensive report of an anaphylactic reaction to latex in a hyperbaric chamber. The lesson drawn from this case record can be summarized as follows: 1) never fail to collect a thorough history; 2) set up a latex-safe hyperbaric chamber when needed; 3) have an emergency kit always near at hand.

The management of patients with primary chronic anal fissure: a position paper.

Anal fissure is one of the most common and painful proctologic diseases. Its treatment has long been discussed and several different therapeutic options have been proposed. In the last decades, the understanding of its pathophysiology has led to a progressive reduction of invasive and potentially invalidating treatments in favor of conservative treatment based on anal sphincter muscle relaxation. Despite some systematic reviews and an American position statement, there is ongoing debate about the best treatment for anal fissure. This review is aimed at identifying the best treatment option drawing on evidence-based medicine and on the expert advice of 6 colorectal surgeons with extensive experience in this field in order to produce an Italian position statement for anal fissures. While there is little chance of a cure with conservative behavioral therapy, medical treatment with calcium channel blockers, diltiazem and nifepidine or glyceryl trinitrate, had a considerable success rate ranging from 50 to 90%. Use of 0.4% glyceryl trinitrate in standardized fashion seems to have the best results despite a higher percentage of headache, while the use of botulinum toxin had inconsistent results. Nonresponding patients should undergo lateral internal sphincterotomy. The risk of incontinence after this procedure seems to have been overemphasized in the past. Only a carefully selected group of patients, without anal hypertonia, could benefit from anoplasty.

Is there a possibility for a glutaraldehyde-free porcine heart valve to grow?

OBJECTIVE: A challenging issue is to create a heart valve with growth and remodeling potential, which would be of great interest for congenital heart valve surgery. This study was performed to evaluate the growth and remodeling potentials of a decellularized heart valve. METHODS: In 4 juvenile sheep (age 12 +/- 1 weeks) with a weight of 24.3 +/- 4.4 kg, a 17-mm diameter decellularized porcine valve was implanted as pulmonary valve replacement. Valve growth was evaluated by transthoracic echocardiography. At explantation, valves were evaluated by gross examination, light microscopy (hematoxylin and eosin, von Kossa, Sirius red, Weigert and Gomori staining), electron microscopy and immunohistochemistry. Atomic absorption spectrometry was performed to evaluate calcium content. RESULTS: All animals showed fast recovery. The mean follow-up was 9.0 +/- 1.8 months. All sheep at least doubled their weight (54.3 +/- 9.2 kg). Echocardiography showed no regurgitation and a flow velocity of 0.7 +/- 0.1 m/s at the latest follow-up. The valve diameter increased from 17.6 +/- 0.5 to 27.5 +/- 2.1 mm (p < 0.018). Gross examination showed a similar wall thickness of the implanted valve and native pulmonary wall, with smooth and pliable leaflets. Histology showed a monolayer of endothelial cells, fibroblast ingrowth and production of new collagen. No calcification was seen at von Kossa staining, confirmed by low calcium content levels of the valve wall and leaflets at atomic absorption spectrometry. CONCLUSIONS: This glutaraldehyde-free heart valve showed not only the absence of calcification, but also remodeling and growth potential.

One-step nested PCR for detection of 2 LTR circles in PBMCs of HIV-1 infected patients with no detectable plasma HIV RNA.

A highly sensitive nested PCR was carried out in order to detect 2 LTR circles as a marker of recent and ongoing viral replication in HIV-1 infected patients with HIV plasma RNA undetectable. This "in house" two-step nested PCR is very sensitive, but it is not feasible for routine tests and presents a high risk of contamination. In order to reduce the time of reactions and crossover contamination, the possibility was explored to carry out a single step nested PCR, in which the two successive amplification rounds are carried out in the same tube. This single step nested PCR has the same sensitivity of the two-step nested, is easy to conduct and requires a short time of reaction. The two different PCR methods were compared and the clinical use of monitoring 2 LTR DNA circles in HIV-1 infected patients with undetectable plasma viral load is discussed.

Glomus tumor of the lower lip. A case report.

A glomus tumor is a benign neoplasm originating from the modified smooth muscle cells of the vascular glomus. This neoplasm was firstly considered by Masson in 1924, and generally it has a solitary lesions but in some cases multiple lesions were described. Differential diagnosis is usually made with Kaposi sarcoma and hemangiopericytoma. The histopathologic examination is essential together with the immunohistochemical study. The clinical case of a 65-year-old man with a glomus tumor of the lower lip is described.

Rhythm-specific pharmacological modulation of subthalamic activity in Parkinson's disease.

The subthalamic nucleus (STN) has a key role in the pathophysiology of Parkinson's disease and is the primary target for high-frequency deep brain stimulation (DBS). The STN rest electrical activity in Parkinson's disease, however, is still unclear. Here we tested the hypothesis that pharmacological modulation of STN activity has rhythm-specific effects in the classical range of EEG frequencies, below 50 Hz. We recorded local field potentials (LFPs) through electrodes implanted in the STN of patients with Parkinson's disease (20 nuclei from 13 patients). After overnight withdrawal of antiparkinsonian therapy, LFPs were recorded at rest both before (off) and after (on) acute administration of different antiparkinsonian drugs: levodopa, apomorphine, or orphenadrine. In the off-state, STN LFPs showed clearly defined peaks of oscillatory activity below 50 Hz: at low frequencies (2-7 Hz), in the alpha (7-13 Hz), low-beta (13-20 Hz), and high-beta range (20-30 Hz). In the on-state after levodopa and apomorphine administration, low-beta activity significantly decreased and low-frequency activity increased. In contrast, orphenadrine increased beta activity. Power changes elicited by levodopa and apomorphine at low frequencies and in the beta range were not correlated, whereas changes in the alpha band, which were globally not significant, correlated with the beta rhythm (namely, low beta: 13-20 Hz). In conclusion, in the human STN, there are at least two rhythms below 50 Hz that are separately modulated by antiparkinsonian medication: one at low frequencies and one in the beta range. Multiple rhythms are consistent with the hypothesis of multiple oscillating systems, each possibly correlating with specific aspects of human STN function and dysfunction.

Long-term inhibition of glioma growth by systemic administration of human PEX.

AIM: The growth of gliomas depends on the balance of factors stimulating or inhibiting angiogenesis, tumor cell invasion and proliferation. The administration of endogenous inhibitors to experimental human gliomas in animal models resulted in a significant inhibition of tumor growth. It is becoming apparent that resistance can develop over time to many types of endogenous inhibitors and seems to be influenced by the tumor type and system of delivery. METHODS: We recently isolated a potent endogenous inhibitor, called human PEX, from human glioma cells in culture. Human PEX is a potent inhibitor of angiogenesis, tumor and endothelial cell proliferation and migration. In this paper, we investigated the ability of human PEX to sustain inhibition of glioma growth for a prolonged period of time. We initially developed a recombinant form of the inhibitor and showed that this form had similar in vitro and in vivo activities to the natural one. Human PEX was then administered to nude mice intracranial human glioma model, in combination with metronomic chemotherapy, for a period of 185 days, starting 15 days after tumor cells implantation. RESULTS: Our data showed that the systemic administration of human PEX mantained a very prolonged inhibition of glioma growth (50% survival of animals treated with 2 mg/kg/days was 160 days vs 24 days of the control) and had a synergistic effect with low dose chemotherapy. Histological analysis of tumors, showed that treatment with PEX was associated with a decrease of vascularity, cell proliferation, and increase in apoptosis. CONCLUSION: These data indicate that human PEX controls tumor growth by separate mechanisms. In addition, treatment with PEX produced well delineated tumors, indicating the persistence of a direct anti-invasive effect of the molecule even after a prolonged period of treatment.

Visualisation of the subthalamic nucleus: a multiple sequential image fusion (MuSIF) technique for direct stereotaxic localisation and postoperative control.

A novel multiple, sequential image fusion (MuSIF) procedure merging stereotaxic CT with frameless magnetic resonance imaging (MRI) is used since June 2000 to visualise and directly localise the subthalamic nucleus (STN) on T2 images. In 13 consecutive Parkinson's cases, intraoperative recording and stimulation verified bilateral electrode implantation guided by fused T2 images. In 85% of sides, final implantation opted for visualised target track. Implanted electrode position on postoperative T2 images matched planned target. Clinical follow-up reproduces literature's best results. This MuSIF technique, effective for direct STN targeting, has practical advantages: MRI can be performed regardless of surgery time; regular MR scanning to correct real image distortion is unneeded; and the need for multiple localising tracks is reduced by enabling us to account for each patient's STN anatomy.

Simultaneous inhibition of glioma angiogenesis, cell proliferation, and invasion by a naturally occurring fragment of human metalloproteinase-2.

Angiogenesis, tumor cell proliferation, and migration are the hallmarks of solid tumors, such as gliomas. This study demonstrates that a fragment derived from the autocatalytic digestion of matrix metalloproteinase (MMP)-2, called PEX, acts simultaneously as an inhibitor of glioma angiogenesis, cell proliferation, and migration. PEX is detected in the cultured medium of various human glioma, endothelial, breast, and prostate carcinoma cell lines. PEX is purified from the medium of glioma cell lines by chromatography, where PEX is constitutively expressed as a free and a TIMP-2-bound form. In human glioma tissue, PEX expression correlates with histological subtype and grade and with alpha v beta 3 integrin expression to which it is bound. Systemic administration of PEX to s.c. and intracranial human glioma xenografts results in a 99% suppression of tumor growth with no signs of toxicity. Thus, PEX is a very promising candidate for the treatment of human malignant gliomas.

Low-dose chemotherapy combined with an antiangiogenic drug reduces human glioma growth in vivo.

This study evaluates the efficacy of the combination of an antiangiogenic drug and conventional chemotherapeutics for the treatment of experimental human gliomas. As an antiangiogenic, we used recombinant human PEX, a fragment of matrix metalloproteinase-2 that we have previously shown to have a significant antimitotic, anti-invasive, and antiangiogenic properties against human glioblastoma in vitro and in vivo. We used carboplatin and etoposide as the two chemotherapeutic drugs routinely used in our institution (Ospedale Maggiore de Milano) for the treatment of malignant gliomas. Conventional chemotherapeutic drugs were administered at high dose or at a low and semicontinuous regimen. Combined treatment of high-dose chemotherapy and PEX did not produce an improvement of survival in comparison with chemotherapy alone, but it was associated with a decrease in tumor volume, vascularity, and proliferative index and an increased apoptosis. All of these animals experienced severe side effects. The longest survival was documented in animals submitted to low and semicontinuous chemotherapy and antiangiogenic treatment. This regimen was associated with no side effects, marked decrease in tumor volume, vascularity, and proliferative index, and an increased apoptosis. Our data suggest that low-dose chemotherapy in combination with PEX can be successfully used against human malignant glioma in vivo.

Giant temporo-occipital sinus pericranii. A case report.

A rare case of a giant, temporo-occipital sinus pericranii is presented. A 38-year-old male presented with minor symptoms of headache and heaviness over an enlarging temporo-occipital bone defect. Within the defect a soft, compressible, mass lesion was observed, which varied in size with changes in intracranial pressure. Radiological imaging demonstrated bone erosion around a fluid filled mass, which on angiography communicated via a series of channels with the transverse sinus. A diagnosis of sinus pericranii was made. Due to the risk of future complication the patient elected to undergo surgery, which successfully resected the mass and obliterated the venous communications with the diploic veins and transverse sinus. The classification, aetiology, differential diagnosis, radiological characteristics and management options relating to sinus pericranii are discussed.

Alpha(v)beta3 and alpha(v)beta5 integrin expression in glioma periphery.

OBJECTIVE: This study analyzed the expression of integrins alpha(v)beta3 and alpha(v)beta5 in glioma tissue and focused on the periphery of high-grade gliomas. METHODS: The analysis was performed with Western blot, immunohistochemistry, and immunofluorescence, by use of two monoclonal antibodies able to recognize the functional integrin heterodimer. The expression of integrin-related ligands and growth factors also was studied. Sections from the tumor periphery were classified as either tumor periphery (light tumor infiltrate or scant visible cells) or peritumor (heavy tumor infiltration). RESULTS: Our data on glioma tissues demonstrated that both integrins were expressed in glioma cells and vasculature and their expression correlated with the histological grade. Alpha(v)beta3 expression was prominent in astrocytic tumors. Both integrins were markers of tumor vasculature, particularly of endothelial proliferation. A high-grade glioma periphery demonstrated a prominent expression of integrin alpha(v)beta3. Cells demonstrating alpha(v)beta3 positivity were identified as tumor astrocytes and endothelial cells by double imaging. The same cells were surrounded by some alpha(v)beta3 ligands and co-localized fibroblast growth factor 2. Matrix metalloproteinase 2 also was found to be co-localized with alpha(v)beta3 in the same cells. Alpha(v)beta3 expression was more relevant in tumor astrocytes. Alpha(v)beta3 integrin and vascular endothelial growth factor expression increased from the periphery to the tumor center. CONCLUSION: Our data support the role of integrins alpha(v)beta3 and alpha(v)beta5 in glioma-associated angiogenesis. In addition, they suggest a role for integrin alpha(v)beta3 in neoangiogenesis and cell migration in high-grade glioma periphery.

Isolated cervical juvenile xanthogranuloma in childhood.

STUDY DESIGN: This is a report of an exceptional case of isolated cervical juvenile xanthogranuloma in a child. OBJECTIVES: This case report draws attention to the fact that isolated xanthogranuloma of the central nervous system should be considered among possible diagnosis of subdural extramedullary spinal masses in children and young adults. SUMMARY AND BACKGROUND DATA: Isolated juvenile xanthogranuloma of the central nervous system is extremely rare. When located in the spinal canal it behaves like any extramedullary mass-occupying lesion. MRI depicts the tumor's association with adjacent structures. In cases in which a subtotal surgical removal was possible, radiotherapy has been indicated. METHODS: A three-year-old girl presented severe pain in the right shoulder and spastic tetraparesis. The MRI showed an intradural extramedullary mass homogeneously enhancing after DTPA-gadolinium infusion. Complete surgical removal of the tumor was performed through open-door laminoplasty. RESULTS: The child was pain free immediately after the surgical removal of the tumor. A gradual complete recovery of the neurologic deficits followed. Open-door laminoplasty provided sufficient operative space, and it minimized the impact on the growing spinal column. CONCLUSIONS: Isolated juvenile xanthogranuloma does not show any predilections of localization inside the central nervous system. Both intracranial and spinal juvenile xanthogranulomas appear isointense in MRI and enhance homogeneously with gadolinium. Whenever possible, total surgical removal alone seems to be curative. Otherwise, a subtotal removal of the tumor might be followed by radiotherapy. Immunohistochemical tests ensure the diagnosis.