Valproic acid could help in the fight against COVID-19: A case-control study.

OBJECTIVE: There is early evidence about Valproic acid (VPA) antiviral effect. Our aim was to investigate the incidence and severity of SARS-CoV-2 infection in VPA users as compared with the general population. MATERIAL AND METHODS: A case-control study nested within a cohort, carried out between March 1 and December 17, 2020. Retrospectively, we identified confirmed SARS-CoV-2 infection patients exposed to VPA in our health department (defined as case). We ascertained VPA regimen (all the time (AT) (292 days) or at least 20% of the study period (notAT) (≥58 days) and if VPA levels were in therapeutic range (ATR) (50-100mcg/mL) in the last 24 months. We calculated the cumulative incidence of SARS-CoV-2 infection and hospital admission in the cases, comparing it with the general unexposed VPA population (controls). RESULTS: During the study period, 6183 PCR+ were detected among 281,035 inhabitants, of these, 746 were hospitalized. 691 patients were on VPA notAT and 628 (90.1%) AT. The indication for VPA use was epilepsy in 54.9%. The incidence of PCR+ was 1.736% (OR 0.785 (95%CI 0.443-1.390) and 1.910% (OR 0.865 (95%CI 0.488-1.533), on VPA notAT and VPA AT patients, respectively vs. 2.201% in people without VPA regimen. Those patients with VPA ATR had a lower risk of PCR + (OR 0.233 (95%CI 0.057-0.951) notAT; OR 0.218 (95%CI 0.053-0.890) AT). Hospital admission incidence was lower in patient on VPA (OR was 0.543 (95% CI 0.076-3.871). CONCLUSION: Patients with VPA within the therapeutic range had a reduction of SARS-Cov-2 infection incidence greater than 75%. There is a downward trend in the risk of COVID-19 admission by SARS-CoV-2 in patients on VPA therapy. These findings warrant further investigation.

Soluble urokinase plasminogen activator receptor (suPAR) as a prognostic marker in COVID-19 patients: a systematic review.

OBJECTIVE: The aim of this study was to perform a systematic review of the usefulness of suPAR as a prognostic marker in non-critical COVID-19 patients. MATERIALS AND METHODS: We carried out a literature search in MEDLINE, Embase, and Web of Science using the following keywords: ("soluble urokinase receptor" OR "urokinase plasminogen activator receptor" OR "suPAR" OR "soluble uPAR" OR "soluble uPA receptor") AND ("COVID-19" OR "SARS-CoV-2"). We included observational studies (descriptive or analytic) that measured plasma suPAR on COVID-19 patients 18 years old or older, with non-critical disease at the beginning of the study. RESULTS: After screening and eligibility assessment, a total of 16 articles were included in the review. Most studies that measured mean differences found that suPAR levels were higher in patients with worse outcomes. The studies that measured diagnostic accuracy concluded that suPAR was highly sensitive and moderately specific to predicting bad outcomes. Studies that performed a survival analysis found that patients with high suPAR levels were more at risk of bad outcomes. Most of the studies included in this review were performed before extensive vaccination and omicron wave. CONCLUSIONS: COVID-19 patients with moderate initial disease and elevated suPAR levels are more at risk of poor outcomes. Larger prospective clinical trials are needed to confirm the results obtained in this review.

Histopathological and virological features of lung, heart and liver percutaneous tissue core biopsy in patients with COVID-19: A clinicopathological case series.

INTRODUCTION: Data on pathological changes in COVID-19 are scarce. The aim of this study was to describe the histopathological and virological findings of postmortem biopsies, and the existing clinical correlations, in people who died of COVID-19. MATERIALS AND METHODS: We performed postmortem needle core biopsies of the chest in 11 people who died of COVID-19 pneumonia. Tissue examination was done by light microscopy and real-time polymerase chain reaction (RTPCR). RESULTS: The age of the patients were between 61 to 94 years. Of the 11 postmortem chest biopsies, lung tissue was obtained in 8, myocardium tissue in 7, and liver tissue in 5. Histologically of lung, the main findings pertaining to the lung were diffuse alveolar damage in proliferative phase (n = 4, 50%), diffuse alveolar damage in exudative and proliferative phase (n = 3, 37.5%), diffuse alveolar damage in exudative (n=1; 12.5%) and acute pneumonia (n = 2, 25%). Necrotising pneumonia, acute fibrinous and organising pneumonia, and neutrophils were detected in one sample each (12.5%). Another case presented myocarditis. RT-PCR showed RNA of SARS-CoV-2 in 7 of the 8 lung samples (87.5%), 2 of the 7 myocardial tissue samples (28.6%), and 1 of the 5 liver tissue samples (20%). CONCLUSION: The postmortem examinations show diffuse alveolar damage, as well as acute or necrotising pneumonia. RT-PCR of SARS-CoV-2 was positive in most lung samples.

Computerized registry of patients with hemorrhagic hereditary telangiectasia (RiHHTa Registry) in Spain: Objectives, methods, and preliminary results. / Registro informatizado de la telangiectasia hemorrágica hereditaria (Registro RiHHTa) en España: objetivos, métodos y resultados preliminares.

INTRODUCTION: Hereditary hemorrhagic telangiectasia (HHT) is a rare disease with autosomal dominant inheritance that causes systemic vascular affectation. MATERIAL AND METHOD: After development a multicentric Spanish national registry, called RiHHTa, main clinical manifestations and diagnostic procedures of the first patients introduced are described. RESULTS: 141 patients were included, of which 91 (64.5%) were women. The mean age at diagnosis was 42 years. Mutations in the ACVRL1 gene predominated over the ENG gene. The initial symptom was recurrent epistaxis in 130 (92.2%) patients and in three (2.1%), brain abscess. Pulmonary arteriovenous (AV) fistula were detected in 36 (45%) of the 79 patients who underwent thoracic CT angiography. The contrast echocardiography detected very few bubbles (grade I) or none, in 36 (45%) of these 79 affected patients. In 43 (67.2%) of the 64 patients with an abdominal CT angiography, hepatic vascular malformations were detected, mostly telangiectasias, AV and arterio-portal fistula, and extrahepatic in 14 (10%) subjects. More than half of the patients were screened for the presence of brain arteriovenous malformations which was found in 3.9% of them. The upper part of the intestinal tube was the most (95%) affected region. CONCLUSION: The RiHHTa Registry allows improving the management of patients with HHT. An inadequate use of thoracic CT angiography and the usefulness of abdominal CT angiography has been detected in order to define subtypes of hepatic vascular involvement and detect extrahepatic vascular involvement.

[Incomplete POEMS syndrome with multicentric Castleman's disease]. / Síndrome de POEMS incompleto asociado a enfermedad de Castleman multicéntrica y amiloidosis.

Castleman's disease (CD) is an atypical lymphoproliferative disorder of unknown cause, characterized by non-clonal nodal hyperplastic growth. Two forms of clinical presentation are currently recognized, one localized and the other multicentric, and four histopathologic variants. It is characterized by generalized lymphadenopathy, hepatosplenomegaly, fever and night sweats. CD may present severe pancytopenia, multi-organ failure, lymphoma evolution and it can sometimes be associated with paraneoplastic syndromes such as POEMS syndrome. Associations of these two entities have been widely described in the current literature, although its less common association with amyloidosis is described as isolated clinical cases. We report a case with this triple association: EC, POEMS and amyloidosis.

Seasonal influenza in octogenarians and nonagenarians admitted to a general hospital: epidemiology, clinical presentation and prognostic factors.

OBJECTIVE: Seasonal influenza is responsible for high annual morbidity and mortality worldwide, especially in elderly patients. The aim of the study was to analyse the epidemiological, clinical and prognostic features of influenza in octogenarians and nonagenarians admitted to a general hospital, as well as risk factors associated with mortality. METHODS: Retrospective, cross-sectional, descriptive study in patients admitted and diagnosed with influenza by molecular biology in the General University Hospital of Alicante from 1 January to 31 April 2015. RESULTS: A total of 219 patients were diagnosed with influenza in the study period: 55 (25.1%) were ≤64 years-old; 77 (35.2%) were aged 65-79; 67 (30.6%) were aged 80-89 years; and 20 (9.1%) were aged ≥90 years. Most flu episodes were caused by influenza A (n=181, 82.6%). Patients aged 80 years or older had lower glomerular filtration rate (mean: 49.7 mL/min vs. 62.2 mL/min; p=0.006), a greater need for non-invasive mechanical ventilation (22% vs 9.3%; p=0.02), greater co-morbidity due to cardiac insufficiency (40.5% vs. 16.4%; p<0.001) and chronic renal disease (32.9 vs. 20%, p=0.03), and greater mortality (19% vs. 2.9%; p<0.001). In a multivariate analysis, mortality was higher in those aged 80 or over (adjusted odds ratio [ORa] 9.2, 95% confidence interval [CI] 1.65-51.1), those who had acquired the flu in a long-term care facility (ORa 11.9, 95% CI 1.06-134), and those with hyperlactataemia (ORa 1.89, 95% CI 1.20-3.00). CONCLUSIONS: Seasonal influenza is a serious problem leading to elevated mortality in octogenarian and nonagenarian patients admitted to a general hospital.

Histone deacetylase inhibitors: mechanism of action and therapeutic use in cancer.

Histone deacetylases (HDACs) remove the acetyl groups of lysine residues of histone tails leading to chromatin compaction and transcriptional repression. In addition, HDACs can also influence transcription-independent events such as mitosis or deoxyribonucleic acid (DNA) repair and deacetylate nonhistone proteins involved in cell proliferation and death, altering their function. Histone deacetylase inhibitors (HDACi) constitute a promising treatment for cancer therapy due to their low toxicity. HDACi have been shown to induce differentiation, cell-cycle arrest, and apoptosis and to inhibit migration, invasion, and angiogenesis in many cancer cell lines. In addition, these compounds inhibit tumor growth in animal models and show antitumor activity in patients. HDACi alone and in combination with a variety of anticancer drugs are being tested in clinical trials, showing significant anticancer activity both in hematological and solid tumors. SAHA (vorinostat, Zolinza) was the first HDACi approved by the US Food and Drug Administration to enter the clinical oncology market for treating cutaneous T-cell lymphoma (CTCL) and is being tested for other malignancies.

Two new eudesmane alcohols from Jasonia glutinosa.

Two new sesquiterpene alcohols have been isolated from the aerial parts of Jasonia glutinosa D. C. The structure of these sesquiterpenes were characterized by 1D and 2D NMR techniques (DQCOSY. TOCSY, NOESY, HMQC and HMBC) as (11R)-eudesm-4-en-11,12-diol and (11R)-eudesmane-5alpha, 11,12-triol.

Prevalence and prevention of deep venous thrombosis of the lower extremities in high-risk pulmonary patients.

Information is lacking about the prevalence of, and the best method of preventing deep venous thrombosis (DVT) of the lower extremities in patients forty years or older with pulmonary disease that keeps them in bed for three consecutive days or more and who are thus at high risk of developing DVT or pulmonary embolism (PE). In this study, 192 high-risk patients, aged forty to ninety-two, received 125I fibrinogen and had daily radioactive scans, venous Doppler, and strain gauge plethysmography. Four preventive methods were used until patients became ambulatory: graded compression stockings (GCS) in 39, elastic bandages (EB) in 33, subcutaneous administration of 5,000 USP units of heparin (HEP) bid in 39, and oral administration of 0.5 g of acetylsalicyclic acid (ASA) bid in 35. Results were compared with those in 46 patients in a control group (CG). Twelve patients in CG, none in GCS, 4 in EB, 1 in HEP, and 2 in ASA developed DVT proved by contrast venography. There was a statistically significant difference between GCS and CG (P less than 0.0003), HEP and CG (P less than 0.0022), and ASA and CG (P less than 0.0148) but not between EB and CG (P greater than 0.10); no significant differences were found between any pair of prophylaxis groups. The significant differences could not be attributed to differences in age, sex, or length of stay in bed. PE occurred in 3 patients in CG and 1 in EB. Hemorrhagic complications occurred in 7 patients in HEP and 4 in ASA, requiring exclusion of 2 patients and 1 patient, respectively, from the study.(ABSTRACT TRUNCATED AT 250 WORDS)

[Combined modality therapeutic program for the control of smoking]. / Programa terapéutico multimodal para el control del tabaquismo.

This investigation presents the results of a multimodal therapeutic programme for the cessation of smoking. The programme included the following elements: self-control techniques, education on a variety of issues on tobacco effects, group dynamic techniques, medical check up and pharmacological support. There were two treatment conditions, one included twelve sessions, and the other eight sessions. All groups received four follow-up sessions in a six month period. Ninety four subjects initiated treatment and 69 (73.4%) completed it. Twenty one subjects (22.3%) stopped smoking and remained abstinent after six months, eleven (11.7%) stopped smoking and relapsed and fourteen (14.7%) stopped smoking but did not attend the last follow-up sessions. Twenty three subjects (24.5%) did not stop smoking but reduced their smoking rate in 50% from initial report. These results were considered as satisfactory when compared with others obtained in similar studies.

Programa terapeutico multimodal para el control del tabaquismo. / Combined modality therapeutic program for smoking control

Se presentan los resultados de un programa terapeutico multimodal para el control del tabaquismo. El programa incluyo tecnicas de autocontrol, educacion sobre diversos aspectos del tabaquismo, manejo de la dinamica del grupo, estudios medicos y apoyo farmacologico. Se impartieron 12 sesiones a unos grupos y 8 a otros y se llevaron a cabo cuatro seguimientos en un periodo de seis meses. Noventa y cuatro personas iniciaron el tratamiento, de las cuales 69 (73.4%) lo completaron. Veintiuna personas (22.3%) dejaron de fumar y siguieron sin fumar a los seis meses, once (11.7%) dejaron de fumar y reincidieron, catorce (14.5%) dejaron de fumar pero no completaron los ultimos seguimientos y vientitres (24.5%) no dejaron de fumar pero redujeron su tabaquismo un 50%. Estos resultados se consideraron satisfactorios al ser comparados con los de estudios similares