Artificial intelligence model for tumoral clinical decision support systems.

BACKGROUND AND OBJECTIVE: Comparative diagnostic in brain tumor evaluation makes possible to use the available information of a medical center to compare similar cases when a new patient is evaluated. By leveraging Artificial Intelligence models, the proposed system is able of retrieving the most similar cases of brain tumors for a given query. The primary objective is to enhance the diagnostic process by generating more accurate representations of medical images, with a particular focus on patient-specific normal features and pathologies. A key distinction from previous models lies in its ability to produce enriched image descriptors solely from binary information, eliminating the need for costly and difficult to obtain tumor segmentation. METHODS: The proposed model uses Artificial Intelligence to detect patient features to recommend the most similar cases from a database. The system not only suggests similar cases but also balances the representation of healthy and abnormal features in its design. This not only encourages the generalization of its use but also aids clinicians in their decision-making processes. This generalization makes possible for future research in different medical diagnosis areas with almost not any change in the system. RESULTS: We conducted a comparative analysis of our approach in relation to similar studies. The proposed architecture obtains a Dice coefficient of 0.474 in both tumoral and healthy regions of the patients, which outperforms previous literature. Our proposed model excels at extracting and combining anatomical and pathological features from brain Magnetic Resonances (MRs), achieving state-of-the-art results while relying on less expensive label information. This substantially reduces the overall cost of the training process. Our findings highlight the significant potential for improving the efficiency and accuracy of comparative diagnostics and the treatment of tumoral pathologies. CONCLUSIONS: This paper provides substantial grounds for further exploration of the broader applicability and optimization of the proposed architecture to enhance clinical decision-making. The novel approach presented in this work marks a significant advancement in the field of medical diagnosis, particularly in the context of Artificial Intelligence-assisted image retrieval, and promises to reduce costs and improve the quality of patient care using Artificial Intelligence as a support tool instead of a black box system.

Epidemiological and Clinical Characteristics of Patients Admitted to a Secondary Hospital with Suspected MPOX Virus Infection: Is HIV Playing a Role?

MPOX (monkeypox) is a zoonotic viral disease, endemic in some Central and West African countries. However, in May 2022, cases began to be reported in non-endemic countries, demonstrating community transmission. Since the beginning of the outbreak, different epidemiological and clinical behaviors have been observed. We conducted an observational study at a secondary hospital in Madrid to characterize suspected and confirmed cases of MPOX epidemiologically and clinically. Besides the general descriptive analysis, we compared data between HIV-positive and HIV-negative subjects; 133 patients were evaluated with suspected MPOX, of which 100 were confirmed. Regarding positive cases, 71.0% were HIV positive, and 99.0% were men with a mean age of 33. In the previous year, 97.6% reported having sex with men, 53.6% used apps for sexual encounters, 22.9% practiced chemsex, and 16.7% went to saunas. Inguinal adenopathies were significantly higher in MPOX cases (54.0% vs. 12.1%, p < 0.001), as the involvement of genital and perianal area (57.0% vs. 27.3% and 17.0% vs. 1.0%, p = 0.006 and p = 0.082 respectively). Pustules were the most common skin lesion (45.0%). In HIV-positive cases, only 6.9% had a detectable viral load, and the mean CD4 count was 607.0/mm3. No significant differences were observed in the disease course, except for a greater tendency towards the appearance of perianal lesions. In conclusion, the MPOX 2022 outbreak in our area has been related to sexual intercourse among MSM, with no severe clinical cases nor apparent differences in HIV and non-HIV patients.

HCV eradication with DAAs differently affects HIV males and females: A whole miRNA sequencing characterization.

Gender-specific consequences after HCV eradication are unexplored. MicroRNAs (miRNAs) play a crucial role in the immune response against viral infections. However, few have highlighted miRNA role in sex-biased disease or therapy response. We aim to assess gender differences reflected in the miRNA expression of HIV/HCV-coinfected patients who achieve sustained virological response (SVR) with direct acting antivirals (DAAs). We conducted a prospective study of miRNA expression in PBMCs from 28 chronic HIV/HCV-coinfected patients (HIV/HCV) at baseline and after achieving SVR with DAAs. Sixteen HIV-monoinfected patients (HIV) and 36 healthy controls (HC) were used as controls. Identification of significant differentially expressed (SDE) miRNAs was performed with generalized linear model and mixed GLMs. We also explored putative dysregulated biological pathways. At baseline, the HIV/HCV patients showed differences in the miRNA profile concerning the HIV group (165 and 102 SDE miRNAs for males and females, respectively). Gender-stratified analysis of HIV/HCV group at baseline versus at SVR achievement showed higher differences in males (80 SDE miRNAs) than in females (55 SDE miRNAs). After SVR, HIV/HCV group showed similar values to HIV individuals, especially in females (1 SDE miRNA). However, ten miRNAs in males remained dysregulated, which were mainly involved in cancer, fatty acid, and inflammatory pathways. Taken together, our results show gender-biased dysregulation in the miRNA expression profile of PBMCs after HCV eradication with DAAs. These differences were normalized in females, while miRNA profile and their target-related pathways in males lack of normalization, which may be related to a high-risk of developing liver-related complications.

Epigenome-wide association study of COVID-19 severity with respiratory failure.

BACKGROUND: Patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the coronavirus disease 2019 (COVID-19), exhibit a wide spectrum of disease behaviour. Since DNA methylation has been implicated in the regulation of viral infections and the immune system, we performed an epigenome-wide association study (EWAS) to identify candidate loci regulated by this epigenetic mark that could be involved in the onset of COVID-19 in patients without comorbidities. METHODS: Peripheral blood samples were obtained from 407 confirmed COVID-19 patients ≤ 61 years of age and without comorbidities, 194 (47.7%) of whom had mild symptomatology that did not involve hospitalization and 213 (52.3%) had a severe clinical course that required respiratory support. The set of cases was divided into discovery (n = 207) and validation (n = 200) cohorts, balanced for age and sex of individuals. We analysed the DNA methylation status of 850,000 CpG sites in these patients. FINDINGS: The DNA methylation status of 44 CpG sites was associated with the clinical severity of COVID-19. Of these loci, 23 (52.3%) were located in 20 annotated coding genes. These genes, such as the inflammasome component Absent in Melanoma 2 (AIM2) and the Major Histocompatibility Complex, class I C (HLA-C) candidates, were mainly involved in the response of interferon to viral infection. We used the EWAS-identified sites to establish a DNA methylation signature (EPICOVID) that is associated with the severity of the disease. INTERPRETATION: We identified DNA methylation sites as epigenetic susceptibility loci for respiratory failure in COVID-19 patients. These candidate biomarkers, combined with other clinical, cellular and genetic factors, could be useful in the clinical stratification and management of patients infected with the SARS-CoV-2. FUNDING: The Unstoppable campaign of the Josep Carreras Leukaemia Foundation, the Cellex Foundation and the CERCA Programme/Generalitat de Catalunya.

Characteristics, complications and outcomes among 1549 patients hospitalised with COVID-19 in a secondary hospital in Madrid, Spain: a retrospective case series study.

OBJECTIVES: To describe demographic, clinical, radiological and laboratory characteristics, as well as outcomes, of patients admitted for COVID-19 in a secondary hospital. DESIGN AND SETTING: Retrospective case series of sequentially hospitalised patients with confirmed SARS-CoV-2, at Infanta Leonor University Hospital (ILUH) in Madrid, Spain. PARTICIPANTS: All patients attended at ILUH testing positive to reverse transcriptase-PCR on nasopharyngeal swabs and diagnosed with COVID-19 between 1 March 2020 and 28 May 2020. RESULTS: A total of 1549 COVID-19 cases were included (median age 69 years (IQR 55.0-81.0), 57.5% men). 78.2% had at least one underlying comorbidity, the most frequent was hypertension (55.8%). Most frequent symptoms at presentation were fever (75.3%), cough (65.7%) and dyspnoea (58.1%). 81 (5.8%) patients were admitted to the intensive care unit (ICU) (median age 62 years (IQR 51-71); 74.1% men; median length of stay 9 days (IQR 5-19)) 82.7% of them needed invasive ventilation support. 1393 patients had an outcome at the end of the study period (case fatality ratio: 21.2% (296/1393)). The independent factors associated with fatality (OR; 95% CI): age (1.07; 1.06 to 1.09), male sex (2.86; 1.85 to 4.50), neurological disease (1.93; 1.19 to 3.13), chronic kidney disease (2.83; 1.40 to 5.71) and neoplasia (4.29; 2.40 to 7.67). The percentage of hospital beds occupied with COVID-19 almost doubled (702/361), with the number of patients in ICU quadrupling its capacity (32/8). Median length of stay was 9 days (IQR 6-14). CONCLUSIONS: This study provides clinical characteristics, complications and outcomes of patients with COVID-19 admitted to a European secondary hospital. Fatal outcomes were similar to those reported by hospitals with a higher level of complexity.

Drug-related and psychopathological symptoms in HIV-positive men who have sex with men who inject drugs during sex (slamsex): Data from the U-SEX GESIDA 9416 Study.

OBJECTIVES: Sexualized intravenous drug use, also known as slamsex, seems to be increasing among HIV-positive men who have sex with men (MSM). Physical and psychopathological symptoms have previously been reported in this population, although research on the subject of slamsex is scarce. The objectives of our study were to describe the psychopathological background of a sample of HIV-positive MSM who engaged in slamsex during the previous year and to compare physical, psychopathological, and drug-related symptoms between these participants and those who engaged in non-injecting sexualized drug use. DESIGN AND METHODS: Participants (HIV-positive MSM) were recruited from the U-Sex study in 22 HIV clinics in Madrid during 2016-17. All participants completed an anonymous cross-sectional online survey on sexual behavior and recreational drug use. When participants met the inclusion criteria, physicians offered them the opportunity to participate and gave them a card with a unique code and a link to access the online survey. The present analysis is based on HIV-positive MSM who had engaged in slamsex and non-injecting sexualized drug use. RESULTS: The survey sample comprised 742 participants. Of all the participants who completed the survey, 216 (29.1%) had engaged in chemsex, and of these, 34 (15.7%) had engaged in slamsex. Participants who engaged in slamsex were more likely to have current psychopathology (depression, anxiety, and drug-related disorders) than participants who engaged in non-injecting sexualized drug use. In addition, participants who engaged in slamsex more frequently reported high-risk sexual behaviors and polydrug use and were more often diagnosed with sexually transmitted infections (STIs) and hepatitis C than those who did not inject drugs. Compared with participants who did not inject drugs, participants who engaged in slamsex experienced more severe drug-related symptoms (withdrawal and dependence), symptoms of severe intoxication (loss of consciousness), and severe psychopathological symptoms during or after slamsex (eg, paranoid thoughts and suicidal behaviors). CONCLUSION: Slamsex is closely associated with current psychiatric disorders and severe drug-related and psychiatric symptoms.

High rates of early HCV reinfection after DAA treatment in people with recent drug use attended at mobile harm reduction units.

BACKGROUND AND AIMS: The World Health Organization recently called for the elimination of hepatitis C virus (HCV) and has identified people who inject drugs (PWID) as a key target population. Clinical trials analyzing currently available all-oral regimens have demonstrated a high degree of efficacy in this population, with a relatively low reinfection rate. There is an urgent need to confirm these data in a harm reduction and active consumption setting. The primary aim of this study was to evaluate the HCV reinfection rate in people with recent drug use followed at low-threshold mobile harm reduction units. METHOD: We included people with recent drug use (smoked or injected heroin/cocaine in the previous 6 months) who received HCV treatment and were attended at two low-threshold mobile harm reduction units over 19 months. Sustained virologic response was assessed 12 weeks after therapy (SVR12). The incidence density of HCV reinfection was defined as the number of reinfections per 100-person years (PY) using person-time of observation and was stratified by drug consumption at initiation of HCV treatment. Cox proportional hazard regression analysis was used to assess factors associated with reinfection. RESULTS: During the study period, 160 people who used drugs in the past 6 months completed HCV therapy. 122 (73.9%) and 88 (53.3%) reported injecting drug use in the 6 months and 30 days prior to HCV treatment, respectively. The overall SVR12 was 68% in the ITT analysis (reinfection = failure) and 90.7% in the modified intent-to-treat analysis (considering reinfections as response and removing people who were missing SVR data). The cohort at-risk for reinfection (n = 121) included 47 (39.2%) people who initiated HCV treatment with recently reported abstinence. Reinfection was identified in 10 persons (8.3%), and the median time to reinfection was 7.2 (IQR 4.2-18) months. Total follow-up time at-risk was 101.1-PY (median 0.6 years, IQR 0.3-1.3). The overall incidence of reinfection was 9.8 per 100-PY (95% CI 4.7,18.2). The incidence of reinfection was higher amongst those who had injected drugs in the previous 6 months (16.7 [95%CI 8.0; 30.7] per 100-PY) and in the previous 30 days (18.9 [95% CI 8.1; 37.2] per 100-PY). In the adjusted analysis, only injecting drugs use in the month prior to initiation of HCV therapy was associated with reinfection (aHR 8.7, 95%CI 1.0; 73.6; p 0.04). CONCLUSION: High efficacy of HCV treatment, was found in people with recent drug use attended and followed at low-threshold mobile harm reduction units. The high rate of early HCV reinfections in this setting should promote surveillance for reinfection at 7-month intervals after ending the treatment or earlier.

Evaluation of dried blood spot samples for screening of hepatitis C and human immunodeficiency virus in a real-world setting.

Both hepatitis C virus (HCV) infection and human immunodeficiency virus (HIV) infection are underdiagnosed, particularly in low-income countries and in difficult-to-access populations. Our aim was to develop and evaluate a methodology for the detection of HCV and HIV infection based on capillary dry blood spot (DBS) samples taken under real-world conditions. We carried out a cross-sectional study of 139 individuals (31 healthy controls, 68 HCV-monoinfected patients, and 40 HCV/HIV-coinfected patients). ELISA was used for anti-HCV and anti-HIV antibody detection; and SYBR Green RT-PCR was used for HCV-RNA detection. The HIV serological analysis revealed 100% sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). The HCV serological analysis revealed a sensitivity of 92.6%, specificity of 100%, PPV of 100%, and NPV of 79.5%. Finally, the HCV-RNA detection test revealed a detection limit of 5 copies/µl with an efficiency of 100% and sensitivity of 99.1%, specificity of 100%, PPV of 100%, and NPV of 96.9%. In conclusion, our methodology was able to detect both HCV infection and HIV infection from the same DBS sample with good diagnostic performance. Screening for HCV and HIV using DBS might be a key strategy in the implementation of national programs for the control of both infections.

[Granular cell tumor of the esophagus: description of an infrequent benign tumor]. / Tumor esofágico de células granulares: descripción de un tumor benigno poco frecuente.

Granular cell tumors (GCT) are infrequent tumors first described by Abrikossoff in 1926. Gastrointestinal involvement occurs in about 6% of GCT, the esophagus being the most frequent location. These tumors are usually benign and asymptomatic and are usually found incidentally when an upper gastrointestinal endoscopy is carried out for another reason, showing an isolated polyp or sessile submucosal nodule, covered by intact yellowish mucosa and with firm consistency. Endoscopic ultrasonography has significantly improved the diagnosis of these lesions. Nowadays endoscopic mucosectomy is the treatment of choice of esophageal GCT with a low frequency of complications. Histologic analysis of the surgical specimen shows specific characteristics such as positivity for S-100 protein. We present two new cases of esophageal GCT that were diagnosed recently and discuss the most relevant features of this infrequent disease.

Long term failure of miltefosine in the treatment of refractory visceral leishmaniasis in AIDS patients.

We carried out a retrospective and descriptive study of 4 HIV infected patients with relapsing visceral leishmaniasis (VL) seen at 2 tertiary-care hospitals in Spain during the last 6 y, in whom miltefosine was used as a compassionate use treatment at a dosage of 50 mg b.i.d. Patients had a medium CD4 lymphocyte count of 69 cells/microl and were C stage. All patients received at least 2 different anti-leishmanial drugs and had at least 3 relapses before miltefosine treatment (range 3-7). Three patients were treated with miltefosine at a standard dose of 50 mg b.i.d. for 28 d, and the other during 12 months. Despite an initial symptomatic improvement, miltefosine treatment failed to eradicate the infection in all cases. We conclude that the use of miltefosine alone is not strong enough to cure relapsing VL in HIV-1 controlled infected patients.