Neutralizing antibodies for SARS-CoV-2 infection.

The COVID-19 pandemic has boosted significant research in developing monoclonal antibodies (mAbs) to treat and prevent SARS-CoV-2 infection. Clinical trials have shown that mAbs are safe and effective in preventing hospitalization and death in patients with mild to moderate COVID-19 risk factors for progression. mAbs have also been effective for treating severe disease in seronegative patients and preventing COVID-19. So far, studies have been carried out in a largely unvaccinated population at a time when the omicron variant was not described. Future research should address these limitations and provide information on specific population groups, including immunosuppressed and previously infected individuals.

Potentially inappropriate medications in older adults living with HIV.

OBJECTIVES: We assessed the prevalence of potentially inappropriate medication (PIM) among older (≥ 65 years) people living with HIV (O-PLWH) in the region of Madrid. METHODS: We analysed the dispensation registry of community and hospital pharmacies from the Madrid Regional Health Service (SERMAS) for the period between 1 January and 30 June 2017, looking specifically at PIMs according to the 2019 Beers criteria. Co-medications were classified according to the Anatomical Therapeutic Chemical (ATC) classification system. RESULTS: A total of 6 636 451 individuals received medications. Of these individuals, 22 945 received antiretrovirals (ARVs), and of these 1292 were O-PLWH. Overall, 1135 (87.8%) O-PLWH were taking at least one co-medication, and polypharmacy (at least five co-medications) was observed in 852 individuals (65.9%). A PIM was identified in 482 (37.3%) O-PLWH. Factors independently associated with PIM were polypharmacy [adjusted odds ratio (aOR) 7.08; 95% confidence interval (CI) 5.16-9.72] and female sex (aOR 1.75; 95% CI 1.30-2.35). The distribution of PIMs according to ATC drug class were nervous system drugs (n = 369; 28.6%), musculoskeletal system drugs (n = 140; 10.8%), gastrointestinal and metabolism drugs (n = 72; 5.6%), cardiovascular drugs (n = 61; 4.7%), respiratory system drugs (n = 13; 1.0%), antineoplastic and immunomodulating drugs (n = 10; 0.8%), and systemic anti-infectives (n = 2; 0.2%). Five drugs accounted for 84.8% of the 482O PLWH with PIMs: lorazepam (38.2%), ibuprofen (18.0%), diazepam (10.2%), metoclopramide (9.9%), and zolpidem (8.5%). CONCLUSIONS: Prescription of PIMs is highly prevalent in O-PLWH. Consistent with data in uninfected elderly people, the most frequently observed PIMs were benzodiazepines and nonsteroidal anti-inflammatory drugs . Targeted interventions are warranted to reduce inappropriate prescribing and polypharmacy in this vulnerable population.

Luminescent pentafluorophenyl-cycloplatinated complexes: synthesis, characterization, photophysics, cytotoxicity and cellular imaging.

Luminescent mono(pentafluorophenyl) cycloplatinated complexes [Pt(C^N-κC,N)(HC^N-κN)(C6F5)] [HC^N = Hthpy (2-(2-thienyl)pyridine) 2a, Hbt (2-phenylbenzothiazole) 2b, Hpq (2-phenylquinoline) 2c] have been prepared by C­H activation of a HC^N ligand in the corresponding [Pt(HC^N-κN)2(C6F5)2] (1a, 1b, 1c) complexes. Complexes 2 evolve in DMSO solution into solvate complexes and we present here successful routes for the synthesis of [Pt(C^N)(C6F5)(DMSO)] (C^N = thpy 3a, bt 3b). They have been fully characterized (X-ray for 1a, 1c, 2b, 3a and 3b), their electronic absorption and emission properties have been investigated and DFT and TD-DFT calculations for 1a, 1c, 2b and 3a have been carried out. Complexes 3a, 3b and [Pt(ppy)(C6F5)(DMSO)] 4 (Hppy = 2-phenylpyridine) show remarkable stability in a mixed DMSO-cellular medium and their cytotoxicity towards the human lung tumor (A549) and bronchial epithelial non-tumorigenic (NL20) cell lines has been evaluated by MTS assays. Their cellular localization in A549 and NL20 human cells and in mouse embryonic fibroblasts obtained from lungs (LMEFs) has also been investigated by fluorescence microscopy.

Increased risk of non-AIDS-related events in HIV subjects with persistent low CD4 counts despite cART in the CoRIS cohort.

The aim was to analyze clinical complications in HIV-infected subjects who persistently maintain low CD4 levels despite virological response to cART in the Spanish CoRIS cohort. The main inclusion criteria were CD4 counts <200cells/mm(3) at cART-initiation and at least 2years under cART achieving a viral load <500copies/mL. Those patients with CD4 counts <250cells/mm(3) 2years after cART were classified as the Low-CD4 group, and clinical events were collected from this time-point. Poisson regression models were used to calculate incidence rate ratios of death, AIDS-defining events, serious non-AIDS-defining events (NAE) and of each specific NAE category (non-AIDS-defining malignancies (non-ADM), cardiovascular, kidney- and liver-related events). Of 9667 patients in the cohort, a total of 1128 met the criteria and 287 (25.4%) were classified in the Low-CD4 group. A higher risk of death (aIRR: 4.71; 95% CI: 1.88-11.82; p-value=0.001) and of non-ADM were observed in this group (aIRR: 2.23; 95% CI: 1.07-4.63; p=0.03). Our results stress the need to control accelerated aging in this population to counter their increased risk of non-AIDS-defining diseases, particularly cancer, and are consistent with the concept that clinical complications are potentially affected by genetics and lifestyle.

Association of torque teno virus (TTV) and torque teno mini virus (TTMV) with liver disease among patients coinfected with human immunodeficiency virus and hepatitis C virus.

Torque teno virus (TTV) and torque teno mini virus (TTMV) have been potentially related to liver diseases. The aim of the study was to quantify TTV and TTMV in human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients to study the relationship between the TTV and TTMV viral loads and the severity of liver disease. We carried out a cross-sectional study in 245 patients coinfected with HIV and HCV (HIV/HCV-group), 114 patients monoinfected with HIV (HIV-group), and 100 healthy blood donors (Control-group). Plasma samples were tested for TTV and TTMV by quantitative real-time polymerase chain reaction (PCR). The prevalences of TTV and TTMV infections in the HIV/HCV-group and the HIV-group were significantly higher than the Control-group (p < 0.05). Furthermore, TTV and TTMV coinfections were found in 92.2 % (226/245) in the HIV/HCV-group, 84.2 % (96/114) in the HIV-group, and 63 % (63/100 %) in the Control-group (p ≤ 0.05). HIV/HCV-coinfected patients with HIV viral load ≥50 copies/mL and patients with severe activity grade had the highest viral loads of TTV and TTMV (p ≤ 0.05). HIV/HCV-coinfected patients with high TTV load (>2.78 log copies/µL) had increased odds of having advanced fibrosis or severe necroinflammatory activity grade in the liver biopsy. Moreover, HIV/HCV-coinfected patients with high TTMV load (>1.88 log copies/µL) had decreased odds of having no/minimal fibrosis and no/mild activity grade, and increased odds of having a high fibrosis progression rate. In conclusion, TTV and TTMV might play a role in the development of liver disease in immunodeficiency patients, such as the patients coinfected with HIV and HCV.

Soluble Fas and Fas ligand in HIV/HCV coinfected patients and impact of HCV therapy.

The aim of this study was to evaluate the influence of clinical and epidemiological characteristics of 183 HIV/HCV coinfected patients and HCV clearance after antiviral treatment on serum sFas and sFasL levels. Thirty out of 183 patients underwent HCV antiviral therapy with IFN-α + RBV for a duration of 48 weeks. HCV genotype 1 and homeostasis model assessment for insulin resistance (HOMA-IR) had a significant positive relationship, and CD4+/µL had a significant negative relationship with sFas (R-square = 0.582; p < 0.001) and sFasL (R-square = 0.216; p < 0.001) in multivariate linear regression analysis. HCV genotype 1 was the only significant variable associated with the sFas/sFasL ratio (R-square = 0.201; p < 0.001). sFas and sFasL levels had positive significant correlations with serum sICAM-1, sVCAM-1, and HOMA levels (p < 0.05). Among patients on IFN-α + RBV therapy, 15 patients showed a sustained virologic response (SVR), while 15 patients were non-responders (NR). Patients with SVR had significant decreases in sFas (p = 0.008) and sFas/sFasL ratio (p = 0.002), while non-responders had a significant increase in sFasL values (p = 0.013). In conclusion, HCV genotype 1, high HOMA, and low CD4+/µL were associated with high serum levels of sFas and sFasL, which indicate higher levels of inflammation and, possibly, increased cardiovascular risk. Moreover, response to HCV antiviral therapy is known to reduce inflammation.

Impact of liver steatosis on the correlation between liver stiffness and fibrosis measured by transient elastography in patients coinfected with human immunodeficiency virus and hepatitis C virus.

We assessed the effect of different hepatic conditions such as fibrosis, steatosis and necroinflammatory activity on liver stiffness as measured by transient elastography in HIV/HCV-coinfected patients. We studied all consecutive HIV/HCV-coinfected patients who underwent liver biopsy and elastography between January 2007 and December 2008. Liver fibrosis was staged following METAVIR Cooperative Study Group criteria. Steatosis was categorized according to the percentage of affected hepatocytes as low (≤10%), moderate (<25%) and severe (≥25%). A total of 110 patients were included. Fibrosis was distributed by stage as follows: F0, n = 13; F1, n = 47; F2, n = 29; F3, n = 18; and F4, n = 3. Liver biopsy revealed the presence of hepatic steatosis in 68 patients (low to moderate, n = 53; and severe n = 15). By univariate regression analysis, fibrosis, necroinflammatory activity, and the degree of steatosis were correlated with liver stiffness. However, in a multiple regression analysis, steatosis and fibrosis were the only independent variables significantly associated with liver stiffness. With a cut-off of 9.5 kPa to distinguish patients with F ≤ 2 from F ≥ 3, elastography led to a significantly higher number of misclassification errors (25%vs 5%; P = 0.014), most of which were false positives for F ≥ 3. Our study suggests that the correlation between liver stiffness and fibrosis as estimated by transient elastography may be affected by the presence of hepatic steatosis in HIV/HCV-coinfected patients.

[Accuracy of pedicle screw insertion in the thoracolumbar spine using image-guided navigation]. / Fiabilidad del navegador en la colocación de tornillos pediculares toracolumbares.

INTRODUCTION: Computer image guidance is one of the most significant technologic advancements in the spine surgery, because preoperative or intraoperative images can be used for multiplanar, three-dimensional intraoperative navigation. MATERIAL AND METHODS: We performed a prospective clinical study to assess the accuracy of pedicle screw insertion using an optoelectronic navigation system (SurgiGATE Spine 2.1 Medivision). The study population included 29 patients with diverse disorders of the thoraco- lumbar spine (degenerative 54%, spondylolisthesis 21%, fractures 14%, scoliosis 7% and spondylodiscitis 4%). One patient was excluded from the study because problems with the specific instruments or the computer system. Pre and post-operative axial computed tomography images were obtained for each patient and analyzed by two independent radiologists to placement accuracy. The correct location was defined accord to Heary scale in 5 grades. RESULTS: 163 image-guided thoraco-lumbar pedicle screws were placed 29 in the thoracolumbar spine and 134 in the lumbosacral spine. We achieved a completely intraosseous placement (Grade I) in 99.4% of lumbosacral spine screws and 100% of thoracolumbar spine screws. Only one misplaced screw (Grade III) in the pedicle of L III in the concavity of a scoliosis was reported. No implant related complications were noted. CONCLUSIONS: The low rate of misplaced screws in this prospective study compares favorably with previously published results. Our initial results indicate that Image-guided spinal surgery is a safe technique which improves surgical performance during posterior transpedicle stabilization.

Accuracy of acoustic rhinometry versus computed tomography in the evaluation of nasal cavity in patients with nasal polyposis.

BACKGROUND: Acoustic rhinometry (AR) accuracy in the diagnosis and follow-up of nasal polyps is as yet unclear. Our objective was to study its accuracy compared with computed tomography (CT) in patients with nasal polyps. METHODS: We studied 29 patients diagnosed of nasal polyposis by nasal endoscopy. In all patients sinunasal CT-scan, AR and nasal nitric oxide (NO) were assessed. Nasal volumes between 0 and 5 (V(0-5)) and 5 and 9 (V(5-9)) centimetres from nasal inlet were measured with AR and CT-scan, by using Pearson and intraclass correlation coefficient tests. RESULTS: All patients (29,79% males, mean age 48.2 yr [range 34-61]) had nasal polyps (score 2-3 on Lildholdt classification, score 0-3). Measurements (right plus left sides) were: AR 8.9 +/- 0.8 cm(3) (V(0-5)) and 15.5 +/- 3.6 cm(3)(V(5-9)); CT 6.5 +/- 0.4 cm(3) (V(0-5)) and 6.3 +/- 0.8 cm(3) (V(5-9)). Pearson correlation was r = 0.67 (p < 0.01) for V(0-5) and r = 0.62 (p < 0.05) for V(5-9). Intraclass correlation coefficient test was 0.51 (V(0-5)) and 0.28 (V(5-9)) for consistency; and 0.43 (V(0-5)) and 0.23 (V(5-9)) for absolute agreement. Low levels of NO (312.3 +/- 43.8 ppb) were found and the correlation between NO levels and volumes (V(0-5) or V(0-9)) measured by AR was not statistically significant. CONCLUSIONS: Compared to CT-scan, AR measurements accurately reflect the geometry of nasal cavity volumes in patients with nasal polyps, with a better assessment in the anterior part of the nasal cavity.

Diagnosis of advanced fibrosis in HIV and hepatitis C virus-coinfected patients via a new noninvasive index: the HGM-3 index.

BACKGROUND: Noninvasive tests are increasingly being used for the assessment of liver fibrosis. We aimed to develop a serum index for the identification of advanced fibrosis (F>or=3) in HIV/hepatitis C virus (HCV)-coinfected patients. METHODS: We carried out a cross-sectional study on a group of 195 patients comprised of an estimation group (EG; n=127) and a validation group (VG; n=68) who all underwent liver biopsy and had not received previous interferon therapy. Liver fibrosis was estimated using the METAVIR score. We developed a new serum index (HGM-3) dependent on levels of platelets, alkaline phosphatase, hepatic growth factor, tissue inhibitor of metalloproteinase-1 and hyaluronic acid. RESULTS: In the EG, the area under the receiver operating characteristic curve (AUC-ROC) of HGM-3 for identification of F>or=3 was 0.939 [95% confidence interval (CI) 0.899, 0.979] which was significantly higher than the AUC-ROC of the HGM-2, FIB-4, aspartate aminotransferase to platelet ratio (APRI) and Forns' indexes. With HGM-3 <0.135 for F<3, 57 patients were correctly identified and two patients were misclassified. We found the presence of F<3 with 96.6% certainty. The negative likelihood ratio (LR) was <0.1 and the diagnostic odds ratio (DOR) was >40. With HGM-3 >0.570 in the EG for F>or=3, 31 patients were correctly identified, and five patients were misclassified. We found the presence of F>or=3 with 86.1% certainty. The positive LR was >12 and the DOR was >40. For the VG, the diagnostic accuracy values were similar to the values for the EG. CONCLUSIONS: HGM-3 appears to be an accurate noninvasive method for the diagnosis of bridging fibrosis and cirrhosis in HIV/HCV-coinfected patients.

Comparison of transient elastography and liver biopsy for the assessment of liver fibrosis in HIV/hepatitis C virus-coinfected patients and correlation with noninvasive serum markers.

Transient elastography (FibroScan) is a novel, rapid and noninvasive technique to assess liver fibrosis. Our objective was to compare transient elastography (TE) and other noninvasive serum indexes as alternatives to liver biopsy in HIV/hepatitis C virus (HCV)-coinfected patients. The fibrosis stage (METAVIR Score), TE, the aspartate aminotransferase-to-platelet ratio index, the Forns fibrosis index, FIB-4 and HGM-2 indexes were assessed in 100 patients between January 2007 and January 2008. The diagnostic values were compared by calculating the area under the receiver operating characteristic curves (AUROCs). Using TE, the AUROC (95% CI) of liver stiffness was 0.80 (0.72-0.89) when discriminating between F 2, 0.93 (0.85-1.00) when discriminating between F 3 and 0.99 (0.97-1.00) when discriminating between F or= 3, the AUROCs of TE were significantly higher than those obtained with the other four noninvasive indexes. Based on receiver operating characteristic curves, three cutoff values were chosen to identify F or= 3 (>or=11 kPa) and F4 (>or=14 kPa). Using these best cutoff scores, the negative predictive value and positive predictive value were 81.1% and 70.2% for the diagnosis of F or= 3 and 100% and 57.1% for the diagnosis of F4. Thus, Transient elastography accurately predicted liver fibrosis and outperformed other simple noninvasive indexes in HIV/HCV-coinfected patients. Our data suggest that TE is a helpful tool for guiding therapeutic decisions in clinical practice.

Noninvasive diagnosis of liver fibrosis in patients with HIV infection and HCV/HBV co-infection.

The measurement of fibrosis stage critically affects the identification of the progression of liver disease, the establishment of a prognosis and therapeutic decision making. Liver biopsy has been the single, most useful method to determine the degree of liver fibrosis (LF), but with recognized limitations, mainly associated with its invasiveness. In recent years, alternative noninvasive methods have been developed, including imaging methods, such as transient elastometry, and assays based on serum biomarkers. This article reviews the available studies evaluating the value of various noninvasive methods for the assessment of LF in patients with HIV-infection and HBV/HCV co-infection, and makes recommendations on how to best use and combine them in clinical practice.

[Clinical outcome 6 years after autologous hematopoietic stem cell transplantation in multiple sclerosis]. / Resultado clínico a 6 años del trasplante autólogo de progenitores hematopoyéticos en la esclerosis múltiple.

INTRODUCTION: Autologous hematopoietic stem cell transplantation (AHSCT) remains as an experimental treatment for severe forms of multiple sclerosis (MS). We describe the clinical outcome of 14 patients included in a protocol of AHSCT after a median follow-up period of 6 years. METHODS: 14 patients (5 relapsing-remitting and 9 secondary progressive) with a median number of relapses in the year before of 3 (1-7), Expanded Disability Status Scale (EDSS) of 6 (4.5-6.5) and decile of the multiple Sclerosis Severity Store (MSSS) 9 (7-10) were included. The procedure included carmustine, cyclophosphamide, antithymocyte globulin and T-cell depletion by CD34+ selection. RESULTS: The 4.5-year progression-free survival was 71%. The 6 year actuarial probability of progression-free survival was 62.5% and the disease activity-free survival of 7.1%. The median EDSS was 6 (4-8.5) and the MSSS 8 (5-10). Only 2 patients presented enhanced T1 lesions. No long-term complications related to the procedure were observed. CONCLUSION: AHSCT cannot be deemed a curative treatment but may cause prolonged stabilisation or change the aggressive course of the disease.

Primary neuroendocrine small cell undifferentiated carcinoma of the parotid gland.

Neuroendocrine small cell carcinoma is a malignant neoplasm that most frequently arises in the lung. Salivary gland involvement is rare, and the parotid is the main gland affected. We describe the fine-needle aspiration (FNA) cytology findings, the immunophenotypical study and the differential diagnosis of a small cell carcinoma that presented in the parotid of a 91-year-old man. The tumour was treated only with radiotherapy and presented a complete response, with no evidence of the disease after three years of follow-up. This is the first case reported in the literature with good outcome after exclusive irradiation.

Occipital condyle syndrome secondary to bone metastases from rectal cancer.

Skull-base metastases are very unfrequent. Occipital condyle syndrome (OCS) is usually underdiagnosed. Until now few cases have been reported in the literature. We present a 71-year-old woman with metastatic rectum adenocarcinoma, with right occipital headache and ipsilateral hypoglossal palsy, diagnosed by computed tomography and magnetic resonance imaging of OCS due to a skull-base metastasis and treated with radiation therapy.

Identification of liver fibrosis in HIV/HCV-coinfected patients using a simple predictive model based on routine laboratory data.

We constructed noninvasive models to predict significant fibrosis (F > or = 2) and advanced fibrosis (F > or = 3) among human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients, naïve for anti-HCV treatment. A total of 296 patients with liver biopsy were randomly assigned to an estimation group (EG = 226; 70%) and a validation group (VG = 70; 30%). We developed the Hospital Gregorio Marañón (HGM)-1 index, based on platelet count, aspartate aminotransferase (AST) and glucose, to predict F > or = 2 and the HGM-2 index, based on platelet count, international normalized ratio, alkaline phosphatase and AST to predict F > or = 3. The area under the receiver operating characteristic curves (AUROCs) of the HGM-1 index for the EG and the VG were 0.807 and 0.712 respectively. The AUROCs of the HGM-2 index for the EG and the VG were 0.844 and 0.815 respectively. With the HGM-1 index applied to the VG, using best cutoff scores, the negative predictive value (NPV) to exclude F > or = 2 was 54.5% and the positive predictive value (PPV) to confirm F > or = 2 was 93.3%. With the HGM-2 index applied to the VG, using best cutoff scores, the NPV to exclude F > or = 3 was 92.3, and the PPV to confirm F > or = 3 was 64.3%. Thus, HGM-2 accurately predicted F > or = 3 among HIV/HCV-coinfected patients. HGM-1 was less accurate at predicting F > or = 2.