Clinical experience with integrase inhibitors in HIV-2-infected individuals in Spain.

BACKGROUND: HIV-2 is a neglected virus despite estimates of 1-2 million people being infected worldwide. The virus is naturally resistant to some antiretrovirals used to treat HIV-1 and therapeutic options are limited for patients with HIV-2. METHODS: In this retrospective observational study, we analysed all HIV-2-infected individuals treated with integrase strand transfer inhibitors (INSTIs) recorded in the Spanish HIV-2 cohort. Demographics, treatment modalities, laboratory values, quantitative HIV-2 RNA and CD4 counts as well as drug resistance were analysed. RESULTS: From a total of 354 HIV-2-infected patients recruited by the Spanish HIV-2 cohort as of December 2017, INSTIs had been given to 44, in 18 as first-line therapy and in 26 after failing other antiretroviral regimens. After a median follow-up of 13 months of INSTI-based therapy, undetectable viraemia for HIV-2 was achieved in 89% of treatment-naive and in 65.4% of treatment-experienced patients. In parallel, CD4 gains were 82 and 126 cells/mm3, respectively. Treatment failure occurred in 15 patients, 2 being treatment-naive and 13 treatment-experienced. INSTI resistance changes were recognized in 12 patients: N155H (5), Q148H/R (3), Y143C/G (3) and R263K (1). CONCLUSIONS: Combinations based on INSTIs are effective and safe treatment options for HIV-2-infected individuals. However, resistance mutations to INSTIs are selected frequently in failing patients, reducing the already limited treatment options.

High sensitivity and reproducibility of in-house ELISAs using different genotypes of Trypanosoma cruzi.

The adequate choice of Trypanosoma cruzi strains as antigen source for the diagnosis of Chagas disease is still controversial due to differences in terms of accuracy reported between different diagnostic tests. In this study was determined if the genetic variability between different genotypes of T. cruzi (TcI, TcII and TcIV) affect the final diagnosis of Chagas disease. The sensitivity and specificity index of in-house ELISA tests prepared with different T. cruzi strains were evaluated with chagasic and non-chagasic control sera and using the TESA-blot as a reference test. The results of this study revealed that the sensitivity index did not vary, with percentages of 100% for all strains in both tests. However, the specificity index for ELISA tests showed differences between 92% and 98%, but were reduced to 78%-89% when Leishmania-positive sera were included. All ELISAs and TESA-blot prepared with different antigens and the recombinant Wiener test were challenged in an endemic community for Chagas disease in Panama. Both ELISAs and TESA-blot recognized the same positive sera, corroborating the sensitivity indexes (100%) found with the control sera. The TESA-blot maintained the specificity index of 100% and did not display false positives. However, the recombinant Wiener test decreased its sensitivity to 81.25%.

Lymphogranuloma venereum in Barcelona, 2007-2012: the role of seroadaptation in men who have sex with men.

This study describes the incidence rate of reported lymphogranuloma venereum (LGV) in men who have sex with men (MSM) in Barcelona from 2007 to 2012. Epidemiological, clinical and sexual behaviour characteristics of LGV cases are described. Seroadaptive behaviours as a transmission risk factor were assessed by a telephone questionnaire during 2012. Data were handled on a strictly confidential basis. LGV annual rate ratios in MSM were compared with cases from 2007. Differences were statistically analysed with a Poisson test. The incidence rate of LGV in MSM aged 15-69 years ranged from 32·1/105 MSM per year in 2007 to 182·7/105 MSM per year in 2012. In 2012, 31/51 LGV cases (61%) answered the telephone questionnaire, of which 84% (26/31) were HIV positive, 39% (12/31) reported having sex according to their partners' serostatus and 7% (2/31) used strategic positioning. The incidence of LGV has increased since 2007 and mainly affects HIV-positive MSM. It is probable that seroadaptation has facilitated LGV transmission.

Absceso retroperitoneal secundario a espondilodiscitis tuberculosa simulando una hernia inguinal incarcerada.

Tuberculosis is the commonest cause of spinal infection worldwide (9-46%). Tuberculosis spondylodiscitis causes multifocal thoracic and lumbar spinal disease, and big paraspinal and psoas abscesses. It is more frequent in people under 40 who had previous tuberculosis infection and from countries where the illness is endemic. Clinic is non-specific and sub-acute. We report the clinical case of a 29-year-old patient who suffered from pericardic tuberculosis in her childhood and who presents a bilateral retroperitoneal abscess due to tuberculosis spondylodiscitis. Her clinical debut began with left inguinal pain and an irreducible mass at this level that simulated an incarcerated inguinal hernia, which is why surgery was indicated. Due to discrepancies between intraoperative findings and the initial diagnosis, the diagnosis and treatment strategy were changed. The purpose of this case report is to emphasize the challenge that the diagnosis of this pathology represents, due to low incidence in our environment and poor clinical features, which results in late diagnosis and late management.

Interlaboratory reproducibility and proficiency testing within the human papillomavirus cervical cancer screening program in Catalonia, Spain.

In Catalonia, a screening protocol for cervical cancer, including human papillomavirus (HPV) DNA testing using the Digene Hybrid Capture 2 (HC2) assay, was implemented in 2006. In order to monitor interlaboratory reproducibility, a proficiency testing (PT) survey of the HPV samples was launched in 2008. The aim of this study was to explore the repeatability of the HC2 assay's performance. Participating laboratories provided 20 samples annually, 5 randomly chosen samples from each of the following relative light unit (RLU) intervals: <0.5, 0.5 to 0.99, 1 to 9.99, and ≥10. Kappa statistics were used to determine the agreement levels between the original and the PT readings. The nature and origin of the discrepant results were calculated by bootstrapping. A total of 946 specimens were retested. The kappa values were 0.91 for positive/negative categorical classification and 0.79 for the four RLU intervals studied. Sample retesting yielded systematically lower RLU values than the original test (P<0.005), independently of the time elapsed between the two determinations (median, 53 days), possibly due to freeze-thaw cycles. The probability for a sample to show clinically discrepant results upon retesting was a function of the RLU value; samples with RLU values in the 0.5 to 5 interval showed 10.80% probability to yield discrepant results (95% confidence interval [CI], 7.86 to 14.33) compared to 0.85% probability for samples outside this interval (95% CI, 0.17 to 1.69). Globally, the HC2 assay shows high interlaboratory concordance. We have identified differential confidence thresholds and suggested the guidelines for interlaboratory PT in the future, as analytical quality assessment of HPV DNA detection remains a central component of the screening program for cervical cancer prevention.

Prognostic impact of chronic obstructive pulmonary disease and bronchial asthma in patients with heart failure.

PURPOSE: To analyze the impact of chronic obstructive pulmonary disease (COPD) and bronchial asthma on therapeutic management and prognosis of patients with heart failure (HF). METHODS: Analysis of the information collected in a clinical registry of patients referred to a specialized HF unit from January-2010 to June-2012. Clinical profile, treatment and prognosis of patients was evaluated, according to the presence of COPD or asthma. Survival analyses were conducted by means of Kaplan-Meier and Cox's methods. Median follow-up was 1493 days. RESULTS: We studied 2577 patients, of which 251 (9.7%) presented COPD and 96 (3.7%) bronchial asthma. Significant differences among study groups were observed regarding to the prescription of beta-blockers (COPD=89.6%; asthma=87.5%; no bronchopathy=94.1%; p=0.002) and SGLT2 inhibitors (COPD=35.1%; asthma=50%; no bronchopathy=38.3%; p=0.036). Also, patients with bronchial disease received less frequently a defibrillator (COPD=20.3%; asthma=20.8%; no broncopathy=29%; p=0.004). COPD was independently associated with increased risk of all-cause mortality (HR=1.64; 95% CI 1.33-2.02), all-cause death or HF admission (HR=1.47; 95% CI 1.22-1.76) and cardiovascular death or heart transplantation (HR=1.39; 95% CI 1.08-1.79) as compared with patients with no bronchopathy. Bronchial asthma was not significantly associated with increased risk of adverse outcomes. CONCLUSIONS: COPD, but not asthma, is an adverse independent prognostic factor in patients with HF.

Implementation of the use of SPECT-portable for evaluation of surgical margins in breast cancer with indication of ROLL: First results.

OBJECTIVES: Main objective: To compare the effectiveness for checking surgical margins between SPECT-portable and mammography of the piece (RxM). SECONDARY OBJECTIVE: To standardize a pre-operative protocol using SPECT-portable and to evaluate the time required in the use of this technique. MATERIAL AND METHODS: Prospective longitudinal study with 36 patients (39 lesions) diagnosed with breast cancer (CM) with criteria for SNOLL/ROLL. A pre-surgical study of the tumor lesion was performed, after the eco-guided administration of 99mTc-nanocolloids of albumin/99mTc-macroaggregates of albumin, in the tumor lesion. Hybrid images (optical + SPECT) and 3D navigation images with gamma probe are obtained using freehandSPECT. In the operating room, 4-5 images are obtained with freehandSPECT, (I) on skin for tumor location, (II) after exposure of surgical bed for resection guide, (III) of the surgical bed after exeresis, (IV and V) the anterior-posterior and lateral surface of the surgical specimen. The three criteria to decide to extend the margins are: (a) residual activity (cps) at the edges of the surgical bed resection; (b) visual analysis of the uptake in the specimen; (c) a minimum distance of 10 mm from the edges of the specimen to the center of greatest uptake, plus the radius of the lesion. We study the concordance of: the depth measurement between ultrasound and freehandSPECT; the surgical margins between freehandSPECT vs. mammography of the specimen (RxM), considering anatomical pathology (AP) as the gold standard technique as reference; surgical time used with freehandSPECT and RxM. RESULTS: Intraoperative localization was performed in all cases. False negative (FN: no detection margin affected) with freehandSPECT: 9 margins; with RxM: 8. True positive (TP: detection margin affected) with freehandSPECT: 5 margins, with RxM: 6. True negative (TN: consider free margin when healthy) with freehandSPECT: 213 margins; with RxM: 196. Negative predictive value (NPV: probability of negative margin on unaffected part) with freehandSPECT: 95.9%, with RxM: 96.07%. Specificity with freehandSPECT: 96.8%, with RxM: 97%. The concordance of surgical bed margins between freehandSPECT and RxM: 94.5%. Between freehandSPECT and AP: 93.1%. Between RxM and PA: 93.5%, being all statistically significant (p-value <0.000), so we can affirm that both techniques are related or dependent on the reference technique, the PA. Degree of correlation between SPECT-portable and low PA (Kappa index: 0.34, 95% CI [0.22-0.47], and between RxM and moderate PA (Kappa index: 0.42, 95% CI [0.29-0.56], p-value <0.001. Comparison of the successes and failures of both techniques (SPECT-portable and RxM) and PA: Distribution χ2: 0.023 with degree of freedom 1, with value <0.05, so we can affirm that both techniques are similar, since there are no significant statistical differences. Median total OR time: 60.25 min (30-145). Mean freehandSPECT OR time: 5 scans = 10 min. CONCLUSIONS: There are no statistically significant differences in the probability to rule out affective margins that require a second surgery between both techniques (SPECT-portable and RxM) so, the technique performed with SPECT-Portable is a useful and effective procedure, which requires specific training with an optimized and multidisciplinary protocol. The time spent with SPECT-portable is feasible for daily practice.

Lymphogranuloma venereum: a hidden emerging problem, Barcelona, 2011.

From the beginning of 2007 until the end of 2011, 146 cases of lymphogranuloma venereum (LGV) were notified to the Barcelona Public Health Agency. Some 49% of them were diagnosed and reported in 2011, mainly in men who have sex with men. Almost half of them, 32 cases, were reported between July and September. This cluster represents the largest since 2004. This article presents the ongoing outbreak of LGV in Barcelona.

Telemedicine- versus outpatient-based initiation and management of ketogenic diet therapy in children with drug-resistant epilepsy during the COVID-19 pandemic.

INTRODUCTION: Initiation of ketogenic diet therapies (KDT) for pediatric epilepsy is usually done on an inpatient basis and the diet is managed during clinical appointments following a protocol of visits and routine tests. Because of the 2019 coronavirus disease (COVID-19) pandemic and the associated lock-down measures, we switched from outpatient to telemedicine-based KDT initiation. OBJECTIVE: To explore the feasibility, effectiveness, and safety of online KDT initiation and follow-up by comparing a group of children with drug-resistant epilepsy that was managed by telemedicine compared to a group that was treated on an outpatient basis. MATERIALS AND METHODS: An observational study was conducted in two groups of patients with drug-resistant epilepsy who initiated KDT and were followed up with an online versus an outpatient modality by the interdisciplinary KDT team of Hospital Pediatria JP Garrahan in Buenos Aires, Argentina. Dietary compliance, ketosis, retention rate, adverse effects, number of contacts, and clinical outcome were evaluated at 1, 3, and 6 months on the diet. RESULTS: Overall, 37 patients were included, of whom 18 started the KD by telemedicine and 19 on an outpatient basis. Minimum follow-up of the patients was 6 months. All patients received the classic ketogenic diet. No statistical differences between the two groups regarding efficacy and safety of the diet were found. CONCLUSIONS: Our results support the feasibility and safety of initiating and management of KDT by telemedicine. Patients and their families should be carefully selected in order to guarantee a good outcome.

Massive deep vein thrombosis in pregnant women: The importance of individualizing the action plan.

Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), is a potentially lethal condition to be taken into account in pregnant women, where the situation is favored by the characteristic physiological changes of the pregnancy, childbirth and the puerperium. The management of this pathology in this type of patient is based on anticoagulation, with the benefits and drawbacks that this implies. We present the case of a pregnant woman with massive DVT and the issues are discussed, such as the method of delivery (vaginal vs. cesarean section) or the management of treatment (LMWH vs. UFH) in order to obtain the safest situation for the patient.

Clinical profile and causes of death according to ejection fraction in patients with heart failure cared for in a specialized Cardiology unit.

BACKGROUND AND OBJECTIVE: Patients with heart failure are classified into three phenotypes based on left ventricular ejection fraction. This work aimed to compare the clinical profile, treatment, prognosis, and causes of death of patients with heart failure and reduced (<40%, HF-rEF), preserved (≥50%, HF-pEF), or mid-range (40-49%, HF-mrEF) left ventricular ejection fraction. METHODS: An analysis was conducted on the clinical data included in a prospective registry of patients with heart failure who were referred to a specific Cardiology unit from 2010 to 2019. RESULTS: A total of 1404 patients with HF-rEF, 239 patients with HF-mrEF, and 266 patients with HF-pEF were analyzed. Significant differences were observed among the groups in regard to several clinical characteristics and the frequency of prescription of neurohormonal blocking drugs. A multivariate Cox regression revealed an increased risk of all-cause mortality in patients with HF-pEF (hazard ratio 1.36; 95% confidence interval 1.03-1.80; p = 0.028) and patients with HF-mrEF (hazard ratio 1.36; 95% confidence interval 1.03-1.78; p = 0.029) as compared to patients with HF-rEF. Heart failure was the most frequent cause of death in the three subgroups. A higher relative weight of sudden death as a cause of death was observed among patients with HF-rEF while the relative weight of non-cardiovascular causes of death was higher among patients with HF-pEF and HF-mrEF. CONCLUSIONS: This study confirms the existence of significant differences among patients with HF-rEF, HF-mrEF, and HF-pEF with regard to their clinical profile, therapeutic management, prognosis, and causes of death.

[Buschke-Lowenstein Tumor associated to nasopharyngeal condillomatosis]. / Tumor de Buschke-Lowenstein asociado a condilomatosis nasofaríngea.

Giant Acuminata Condyloma or Buschke-Lowenstein Tumor (BLT) is a rare disease characterized typically by its perineal location, local aggressiveness and its cauliflower-like aspect. BLT is associated with Human Papilloma Virus (HPV) infection. Because malignant transformation of BLT is high, radical local excision and histopathological examination are needed. We report a 26-year-old male, seropositive for HIV with giant verrucous lesions in the inguinal, perineal, suprapubic and genital area. Rectosismoidoscopy revealed anal canal involvement. Oropharyngeal papillomatosis was also found. Wide local excision was performed, including inguinoperineal and oropharyngeal lesions. Pathology studies show papillomatosis with koilocytes and no evidence of malignant transformation.

Psoas abscess due to Pasteurella multocida.

Psoas abscess is a pus collection within the muscle compartment. It is a very uncommon entity. It can be primary as a result of haematogenous spread or secondary as a consequence of a direct extension of an infectious focus. Diagnosis is usually delayed because nonspecific clinical presentation. Staphylococcus aureus is the most common organism cultured in this type of abscess. We describe a secondary psoas abscess in an elderly female patient. The patient presented with fever, right groin pain and malaise. Following laboratory, radiological and microbiological analyses the patient was diagnosed as having a psoas abscess due to Pasteurella multocida, which is a Gram negative bacteria, part of the normal oral flora of many animals and can causes human infections after animal scratches or bites. More rarely is to find this organism causing psoas abscesses. Because of insidious clinical presentation, the diagnosis of psoas abscess is a challenge and a high index of suspicion is required. We emphasize the importance of bacteriological confirmation of microorganism involved to choose the correct antibiotics. Percutaneous drainage is the treatment of choice. Open surgical drainage should be reserved if percutaneous drainage fails.

Structurally Uncommon Secondary Metabolites Derived from Endophytic Fungi.

Among microorganisms, endophytic fungi are the least studied, but they have attracted attention due to their high biological diversity and ability to produce novel and bioactive secondary metabolites to protect their host plant against biotic and abiotic stress. These compounds belong to different structural classes, such as alkaloids, peptides, terpenoids, polyketides, and steroids, which could present significant biological activities that are useful for pharmacological or medical applications. Recent reviews on endophytic fungi have mainly focused on the production of novel bioactive compounds. Here, we focus on compounds produced by endophytic fungi, reported with uncommon bioactive structures, establishing the neighbor net and diversity of endophytic fungi. The review includes compounds published from January 2015 to December 2020 that were catalogued as unprecedented, rare, uncommon, or possessing novel structural skeletons from more than 39 different genera, with Aspergillus and Penicillium being the most mentioned. They were reported as displaying cytotoxic, antitumor, antimicrobial, antiviral, or anti-inflammatory activity. The solid culture, using rice as a carbon source, was the most common medium utilized in the fermentation process when this type of compound was isolated.

Iatrogenic tracheal rupture in a patient with acute respiratory distress syndrome due to SARS-CoV-2 pneumonia.

Iatrogenic tracheal rupture (ITR) is a serious complication secondary to procedures such as emergent orotracheal intubation or tracheostomy, among others. The management of ITR depends on the size, extension and location of the injury, along with the patient's respiratory status and comorbidities. The priority of treatment is to keep the airway permeable to ensure adequate ventilation. We present the case of a tracheal rupture after performing a percutaneous tracheostomy, in a patient diagnosed with severe acute respiratory distress syndrome secondary to bilateral interstitial pneumonia due to SARS-Cov-2. The issues are discussed, such as the management (conservative vs. surgical) depending on the features of the injury and the patient, in the extraordinary context that the COVID-19 pandemic has entailed.

Epidemiological Aspects of Maternal and Congenital Toxoplasmosis in Panama.

In Panama, epidemiological data on congenital toxoplasmosis are limited, making it difficult to understand the scope of clinical manifestations in the population and factors that may increase the risk of infection. This study provides insight into the epidemiological situation of maternal and congenital toxoplasmosis in Panama and contributing information on the burden of this disease in Central America. Blood samples were collected from 2326 pregnant women and used for the detection of anti-T. gondii antibodies. A high seroprevalence (44.41%) was observed for T. gondii infection in pregnant women from different regions of Panama, with an estimated incidence rate of congenital toxoplasmosis of 3.8 cases per 1000 live births. The main risk factors associated with T. gondii infection using bivariate statistical analysis were an elementary level education and maternal age range of 34-45 years. Multivariate statistical analyses revealed that in some regions (San Miguelito, North and West regions), the number of positive cases correlated with the presence of pets, stray dogs and the consumption of poultry. In other regions (East and Metropolitan regions), the absence of pets was considered a protective factor associated with negative cases, while the presence of stray cats and the age range of 25-34 years did not represent any risk in these regions.

Antiviral immune response in patients with multiple sclerosis and healthy siblings.

The objective of this study was to determine the immune responses to candidate viral triggers of multiple sclerosis in patients and healthy siblings raised in the same family household. Virus antigen-specific IgG responses to Epstein-Barr virus-derived gene products as well as to human herpersvirus-6, human cytomegalovirus, and measles virus were evaluated in 25 multiple sclerosis patients and compared with 49 healthy full-siblings. IgG responses to the latent Epstein-Barr virus-encoded nuclear antigen-1 (EBNA1) were selectively increased in individuals with multiple sclerosis compared with their unaffected siblings. We conclude that elevated IgG responses towards EBNA1 are associated with the development of multiple sclerosis.

A type I interferon signature in monocytes is associated with poor response to interferon-beta in multiple sclerosis.

The effect of interferon-beta in multiple sclerosis is modest and many patients do not respond to treatment. To date, no single biomarker reliably correlates with responsiveness to interferon-beta in multiple sclerosis. In the present study, genome-wide expression profiling was performed in peripheral blood mononuclear cells from 47 multiple sclerosis patients treated with interferon-beta for a minimum of 2 years and classified as responders and non-responders based on clinical criteria. A validation cohort of 30 multiple sclerosis patients was included in the study to replicate gene-expression findings. Before treatment, interferon-beta responders and non-responders were characterized by differential expression of type I interferon-induced genes with overexpression of the type interferon-induced genes in non-responders. Upon treatment the expression of these genes remained unaltered in non-responders, but was strongly upregulated in responders. Functional experiments showed a selective increase in phosphorylated STAT1 levels and interferon receptor 1 expression in monocytes of non-responders at baseline. When dissecting this type I interferon signature further, interferon-beta non-responders were characterized by increased monocyte type I interferon secretion upon innate immune stimuli via toll-like receptor 4, by increased endogenous production of type I interferon, and by an elevated activation status of myeloid dendritic cells. These findings indicate that perturbations of the type I interferon signalling pathway in monocytes are related to lack of response to interferon-beta, and type I interferon-regulated genes may be used as response markers in interferon-beta treatment.

Iatrogenic tracheal rupture in a patient with acute respiratory distress syndrome due to SARS-CoV-2 pneumonia. / Rotura traqueal iatrogénica en paciente con síndrome de distrés respiratorio agudo por neumonía SARS-CoV-2.

Iatrogenic tracheal rupture is a serious complication secondary to procedures such as emergent orotracheal intubation or tracheostomy, among others. The management of iatrogenic tracheal rupture depends on the size, extension and location of the injury, along with the patient's respiratory status and comorbidities. The priority of treatment is to keep the airway permeable to ensure adequate ventilation. We present the case of a tracheal rupture after performing a percutaneous tracheostomy, in a patient diagnosed with severe acute respiratory distress syndrome secondary to bilateral interstitial pneumonia due to SARS-CoV-2. The issues are discussed, such as the management (conservative vs. surgical) depending on the features of the injury and the patient, in the extraordinary context that the COVID-19 pandemic has entailed.

Frequency of Toxoplasma gondii and Risk Factors Associated with the Infection in Stray Dogs and Cats of Panama.

Stray animals such as dogs and cats have an important role in maintaining the transmission cycles and dissemination of Toxoplasma gondii. Therefore, the objective of this study was to evaluate the frequency of T. gondii in stray dogs and cats in six different regions of Panama and determine risk factors associated with the dynamics of infection in each of the studied regions. Data were obtained using serological tests for the detection of anti-T. gondii IgG and IgM antibodies. The results of this study revealed an overall infection frequency of 23.73%. The infection frequencies found in dog and cat populations were 25.70% and 21.93% respectively, showing no statistically significant difference. Risk factor correlations suggested different infection dynamics depending on the region analyzed. The San Miguelito, North and West regions were more associated with positive cases in dogs with an age range greater than 13 months. Conversely, the Metro, Central and East regions were more associated with negative cases in cats with age ranging between 0 and 5 months. Infection of the parasite in stray animals can be influenced by intrinsic characteristics of each region, which can potentiate different risk factors associated with the different routes of transmission.