HIV and gp120-induced lipid droplets loss in hepatic stellate cells contribute to profibrotic profile.

Liver fibrosis is the excessive accumulation of extracellular matrix proteins, primarily collagen, in response to liver injury caused by chronic liver diseases. HIV infection accelerates the progression of liver fibrosis in patients co-infected with HCV or HBV compared to those who are only mono-infected. The early event in the progression of liver fibrosis involves the activation of hepatic stellate cells (HSCs), which entails the loss of lipid droplets (LD) to fuel the production of extracellular matrix components crucial for liver tissue healing. Thus, we are examining the mechanism by which HIV stimulates the progression of liver fibrosis. HIV-R5 tropic infection was unable to induce the expression of TGF-ß, collagen deposition, α-smooth muscle actin (α-SMA), and cellular proliferation. However, this infection induced the secretion of the profibrogenic cytokine IL-6 and the loss of LD. This process involved the participation of peroxisome proliferator-activated receptor (PPAR)-α and an increase in lysosomal acid lipase (LAL), along with the involvement of Microtubule-associated protein 1 A/1B-light chain 3 (LC3), strongly suggesting that LD loss could occur through acid lipolysis. These phenomena were mimicked by the gp120 protein from the R5 tropic strain of HIV. Preincubation of HSCs with the CCR5 receptor antagonist, TAK-779, blocked gp120 activity. Additionally, experiments performed with pseudotyped-HIV revealed that HIV replication could also contribute to LD loss. These results demonstrate that the cross-talk between HSCs and HIV involves a series of interactions that help explain some of the mechanisms involved in the exacerbation of liver damage observed in co-infected individuals.

HIV-Infected Hepatic Stellate Cells or HCV-Infected Hepatocytes Are Unable to Promote Latency Reversal among HIV-Infected Mononuclear Cells.

Due to a common mode of transmission through infected human blood, hepatitis C virus (HCV) and human immunodeficiency virus (HIV) co-infection is relatively prevalent. In alignment with this, HCV co-infection is associated with an increased size of the HIV reservoir in highly active antiretroviral therapy (HAART)-treated individuals. Hence, it is crucial to comprehend the physiological mechanisms governing the latency and reactivation of HIV in reservoirs. Consequently, our study delves into the interplay between HCV/HIV co-infection in liver cells and its impact on the modulation of HIV latency. We utilized the latently infected monocytic cell line (U1) and the latently infected T-cell line (J-Lat) and found that mediators produced by the infection of hepatic stellate cells and hepatocytes with HIV and HCV, respectively, were incapable of inducing latency reversal under the studied conditions. This may favor the maintenance of the HIV reservoir size among latently infected mononuclear cells in the liver. Further investigations are essential to elucidate the role of the interaction between liver cells in regulating HIV latency and/or reactivation, providing a physiologically relevant model for comprehending reservoir microenvironments in vivo.

Risk factors for irreversible unilateral loss of renal function in patients with deep endometriosis.

Deep endometriosis (DE) can be more aggressive than other types of endometriosis, and may even lead to irreversible severe complications such as complete unilateral loss of renal function. We aimed to describe the clinical and radiologic characteristics of DE patients diagnosed with irreversible unilateral loss of renal function due to unilateral ureteral stenosis and evaluate risk factors for developing this loss. This retrospective cohort study included 436 patients who underwent laparoscopic DE surgery. We evaluated two groups of patients according to preserved (Non-Renal Loss Group; n = 421) or irreversible unilateral damaged renal function (Renal Loss Group; n = 15). Preoperative epidemiologic variables, clinical characteristics, radiologic findings and surgical treatments of all the patients were collected. The Renal Loss Group had a higher infertility rate and a higher proportion of asymptomatic patients. The following radiological variables showed statistically significant differences between the two groups: mean endometrioma diameter, the presence of intestinal DE and negative sliding sign. Multivariate analysis showed that infertility, being asymptomatic, having intestinal DE or torus uterinus/uterosacral ligament DE and a negative sliding sign significantly increased the risk of loss of renal function. Therefore, among patients with these clinical and/or radiological variables, severe urinary tract obstruction should be specifically ruled out.

B. abortus Infection Promotes an Imbalance in the Adipocyte-Osteoblast Crosstalk Favoring Bone Resorption.

Osteoarticular injury is the most common presentation of active brucellosis in humans. Osteoblasts and adipocytes originate from mesenchymal stem cells (MSC). Since those osteoblasts are bone-forming cells, the predilection of MSC to differentiate into adipocytes or osteoblasts is a potential factor involved in bone loss. In addition, osteoblasts and adipocytes can be converted into each other according to the surrounding microenvironment. Here, we study the incumbency of B. abortus infection in the crosstalk between adipocytes and osteoblasts during differentiation from its precursors. Our results indicate that soluble mediators present in culture supernatants from B. abotus-infected adipocytes inhibit osteoblast mineral matrix deposition in a mechanism dependent on the presence of IL-6 with the concomitant reduction of Runt-related transcription factor 2 (RUNX-2) transcription, but without altering organic matrix deposition and inducing nuclear receptor activator ligand kß (RANKL) expression. Secondly, B. abortus-infected osteoblasts stimulate adipocyte differentiation with the induction of peroxisome proliferator-activated receptor γ (PPAR-γ) and CCAAT enhancer binding protein ß (C/EBP-ß). We conclude that adipocyte-osteoblast crosstalk during B. abortus infection could modulate mutual differentiation from its precursor cells, contributing to bone resorption.

Top-down modulation impairs priming susceptibility in complex decision-making with social implications.

Could social context variables prime complex decisions? Could top-down processes impair this priming susceptibility? Complex decisions have been mainly studied from economic and moral perspectives, and Dual Process Theories provide evidence of how these processes could be affected. To address these issues from a political perspective, online experiments were conducted. Participants (n = 252) were asked to choose a face from 4 options, each associated with different frequencies (repetition priming) or with phrases with different emotional valence (emotional priming), for an unspecified task (UST group) or an important task (IMT group). The most repeated face was chosen most in the UST group, and was associated with lower response times. Positive faces were equally chosen by both groups. To compare results in a more ecological situation, a social study was conducted during the 2019 Argentine Presidential Election, including online surveys (n = 3673) and analysis of news media mentioning candidates. The familiarity and trust to each candidate explained the voting-probability for most of them, as well as correlated with their frequency of mentions in the news, their positive associations, and election results. Our results suggest complex decision-making is susceptible to priming, depending on top-down modulation.

Proinflammatory Microenvironment During Kingella kingae Infection Modulates Osteoclastogenesis.

Kingella kingae is an emerging pathogen that causes septic arthritis, osteomyelitis, and bacteremia in children from 6 to 48 months of age. The presence of bacteria within or near the bone is associated with an inflammatory process that results in osteolysis, but the underlying pathogenic mechanisms involved are largely unknown. To determine the link between K. kingae and bone loss, we have assessed whether infection per se or through the genesis of a pro-inflammatory microenvironment can promote osteoclastogenesis. For that purpose, we examined both the direct effect of K. kingae and the immune-mediated mechanism involved in K. kingae-infected macrophage-induced osteoclastogenesis. Our results indicate that osteoclastogenesis is stimulated by K. kingae infection directly and indirectly by fueling a potent pro-inflammatory response that drives macrophages to undergo functional osteoclasts via TNF-α and IL-1ß induction. Such osteoclastogenic capability of K. kingae is counteracted by their outer membrane vesicles (OMV) in a concentration-dependent manner. In conclusion, this model allowed elucidating the interplay between the K. kingae and their OMV to modulate osteoclastogenesis from exposed macrophages, thus contributing to the modulation in joint and bone damage.

[Cystoscopy in the assessment of patients with bladder pain syndrome: Results of a national multicenter observational study.] / La cistoscopia en la evaluación del síndrome de dolor vesical: resultados de un estudio observacional multicéntrico nacional.

OBJECTIVES: To study the use and results of cystoscopy and bladder hydrodistension in the objective assessment of patients with Bladder Pain Syndrome (BPS), in routine clinical practice. MATERIAL AND METHODS: Observational, non-interventional, national, multicenter study carried out in Functional Urology and Urodynamic Units of Spain belonging to the IFU Group. 273 women with BPS who underwent cystoscopy at baseline as a diagnostic tool according to clinical criteria and following the routine clinical practice of each center, were studied. The pre and post hydrodistension findings and the scores of the symptom and Health-Related Quality of Life (HRQoL) questionnaires were described: BPIC-SS, PPBC, PGI-S and EQ-5D-5L. RESULTS: The mean age (SD) was 59 (14) years with a high presence of bladder symptoms: increased voiding frequency (81.7%), nocturia (74%) and urgency (60.4%). 40.7% of cystoscopies were performed under anesthesia and 73.7% uses a standard rigid cystoscope. Hunner lesions were observed in 9.9% of the patients, hypervascularizations (46.2%), glomerulations (23.4%), mild bleeding (6.6%) and scars (2.2%). After hydrodistension, a greater number of grade 1 and 2 lesions were observed. In 51.6% of the patients there were no changes, but in 27.5% slight changes were observed and in 11.4% moderate or severe changes. Symptom and HRQoL questionnaire scores showed no association with cystoscopy findings before and after hydrodistension. CONCLUSIONS: The value of the cystoscopic findings in the SDV has yet to be defined, although it plays a fundamental role in the differential diagnosis. In this observational study, we did not find a correlation of the cystoscopic findings with the symptoms of the patients, measured by validated questionnaires, nor with the HRQoL.

OBJETIVO: Analizar el uso y resultados de la cistoscopia y la hidrodistensión vesical para la evaluación objetiva de pacientes con Síndrome de Dolor Vesical (SDV), en el contexto de práctica clínica habitual.MATERIAL Y MÉTODOS: Estudio observacional, no intervencionista, multicéntrico de ámbito nacional, realizado en Unidades de Urología Funcional y Urodinámica de España pertenecientes al Grupo IFU en el que se analizaron 273 mujeres con SDV a las que se les realizó una cistoscopia a nivel basal como herramienta diagnóstica según criterio clínico y siguiendo la práctica clínica habitual de cada centro. Se describieron los hallazgos pre y post hidrodistensión y las puntuaciones de los cuestionarios de síntomas y de Calidad de Vida Relacionada con la Salud (CVRS): BPIC-SS, PPBC, PGI-S y EQ-5D-5L. RESULTADOS: La edad media (DE) fue de 59 (14) años con gran presencia de síntomas vesicales: frecuencia miccional aumentada (81,7%), nocturia (74,0%) y urgencia (60,4%). El 40,7% de las cistoscopias se realizaron bajo anestesia y en el 73,7% se empleó un cistoscopio rígido estándar. Se observaron lesiones de Hunner en un 9,9% de las pacientes, hipervascularizaciones (46,2%), glomerulaciones (23,4%), sangrado leve (6,6%) y cicatrices (2,2%). Tras la hidrodistensión se observó un mayor número de lesiones grado 1 y 2. En el 51,6% de las pacientes no hubo cambios, pero en el 27,5% se observaron cambios leves y en el 11,4% cambios moderados o graves. Las puntuaciones de los cuestionarios de síntomas y CVRS no mostraron asociación con los hallazgos de la cistoscopia antes y después de la hidrodistensión. CONCLUSIONES: El valor de los hallazgos cistoscópicos en el SDV está aún por definir, aunque juega un papel fundamental en el diagnóstico diferencial. En este estudio observacional no encontramos correlación de los hallazgos cistoscópicos con los síntomas de las pacientes, medidos por cuestionarios validados, ni con la CVRS.

La cistoscopia en la evaluación del síndrome de dolor vesical: resultados de un estudio observacional multicéntrico nacional / Cystoscopy in the evaluation of bladder pain syndrome: results of a national multicenter observational study

Objetivo: Analizar el uso y resultados dela cistoscopia y la hidrodistensión vesical para la evaluación objetiva de pacientes con Síndrome de DolorVesical (SDV), en el contexto de práctica clínica habitual.Material y métodos: Estudio observacional, nointervencionista, multicéntrico de ámbito nacional, realizado en Unidades de Urología Funcional y Urodinámica de España pertenecientes al Grupo IFU en el quese analizaron 273 mujeres con SDV a las que se lesrealizó una cistoscopia a nivel basal como herramientadiagnóstica según criterio clínico y siguiendo la prácticaclínica habitual de cada centro. Se describieron los hallazgos pre y post hidrodistensión y las puntuaciones de los cuestionarios de síntomas y de Calidad de Vida Relacionada con la Salud (CVRS): BPIC-SS, PPBC, PGI-Sy EQ-5D-5L.Resultados: La edad media (DE) fue de 59 (14) añoscon gran presencia de síntomas vesicales: frecuenciamiccional aumentada (81,7%), nocturia (74,0%) y urgencia (60,4%). El 40,7% de las cistoscopias se realizaron bajo anestesia y en el 73,7% se empleó uncistoscopio rígido estándar. Se observaron lesiones deHunner en un 9,9% de las pacientes, hipervascularizaciones (46,2%), glomerulaciones (23,4%), sangradoleve (6,6%) y cicatrices (2,2%). Tras la hidrodistensiónse observó un mayor número de lesiones grado 1 y2. En el 51,6% de las pacientes no hubo cambios,pero en el 27,5% se observaron cambios leves y en el11,4% cambios moderados o graves. Las puntuacionesde los cuestionarios de síntomas y CVRS no mostraronasociación con los hallazgos de la cistoscopia antes ydespués de la hidrodistensión. Conclusiones: El valor de los hallazgos cistoscópicos en el SDV está aún por definir, aunque juega unpapel fundamental en el diagnóstico diferencial. En esteestudio observacional no encontramos correlación delos hallazgos cistoscópicos con los síntomas de las pacientes, medidos por cuestionarios validados, ni con laCVRS.(AU)

Objetives: To study the use and resultsof cystoscopy and bladder hydrodistension in the objective assessment of patients with Bladder Pain Syndrome(BPS), in routine clinical practice.Material and methods: Observational, non-interventional, national, multicenter study carried out inFunctional Urology and Urodynamic Units of Spain belonging to the IFU Group. 273 women with BPS whounderwent cystoscopy at baseline as a diagnostic toolaccording to clinical criteria and following the routineclinical practice of each center, were studied. The preand post hydrodistension findings and the scores of thesymptom and Health-Related Quality of Life (HRQoL)questionnaires were described: BPIC-SS, PPBC, PGI-Sand EQ-5D-5L.Results: The mean age (SD) was 59 (14) years witha high presence of bladder symptoms: increased voiding frequency (81.7%), nocturia (74%) and urgency(60.4%). 40.7% of cystoscopies were performed under anesthesia and 73.7% uses a standard rigid cystoscope. Hunner lesions were observed in 9.9% of thepatients, hypervascularizations (46.2%), glomerulations(23.4%), mild bleeding (6.6%) and scars (2.2%). Afterhydrodistension, a greater number of grade 1 and 2lesions were observed. In 51.6% of the patients therewere no changes, but in 27.5% slight changes wereobserved and in 11.4% moderate or severe changes.Symptom and HRQoL questionnaire scores showed noassociation with cystoscopy findings before and afterhydrodistension.Cconclusions: The value of the cystoscopic findingsin the SDV has yet to be defined, although it plays afundamental role in the differential diagnosis. In this observational study, we did not find a correlation of thecystoscopic findings with the symptoms of the patients,measured by validated questionnaires, nor with theHRQoL.(AU)

Accuracy of Transvaginal Ultrasound Compared to Cystoscopy in the Diagnosis of Bladder Endometriosis Nodules.

OBJECTIVES: To evaluate the accuracy of transvaginal ultrasound (TVUS) in predicting detrusor infiltration and ureteral meatus involvement in patients with bladder endometriosis (BE) to select which cystoscopic procedures could be avoided and, secondarily, to assess the relationship between symptoms and the characteristics of nodules and the association of BE with other forms of endometriosis. METHODS: Patients with BE diagnosed by TVUS were classified according to detrusor infiltration: BE with partial involvement of the muscular layer (group 1) and total muscular layer involvement with bladder protrusion (group 2). We analyzed the accuracy of TVUS compared with subsequently performed cystoscopy, the correlation with symptoms, and the association with other forms of endometriosis. RESULTS: Among the 22 patients included, TVUS showed 9 patients with BE nodules partially affecting the detrusor (group 1) with normal cystoscopic findings (TVUS negative predictive value, 100%). Transvaginal ultrasound detected 13 nodules with total involvement, all visible by cystoscopy (TVUS positive predictive value, 100%). Transvaginal ultrasound also identified ureteral orifices that were free of involvement at greater than 10 mm from the BE nodule in 21 of 22 women (TVUS sensitivity, 95%). Ultrasound criteria for adenomyosis and endometriosis in other locations were present in 20 of 22 patients. CONCLUSIONS: Transvaginal ultrasound can identify the infiltration of BE nodules in the bladder wall and predict cystoscopic findings with great accuracy. Nodules that partially affect the muscular layer have normal cystoscopic findings, thereby obviating the need for this procedure. Bladder endometriosis nodules are commonly associated with other forms of endometriosis and do not usually affect the ureteral meatus.

Primary cryotherapy for localized prostate cancer treatment.

INTRODUCTION: Prostate cryotherapy is an available treatment option for localized prostate cancer (PC) included on minimal invasive therapies but still under evaluation. We started our cryotherapy program in 2008 for selected patients with localized PC. Our objective is to evaluate the oncologic and functional outcomes of primary cryotherapy in men with clinically localized PC. SUBJECTS AND METHODS: We retrospectively evaluated all patients who underwent primary cryotherapy for localized PC treatment at our center between January 2008 and December 2017. In order to downsize prostates between 40 and 60cc neoadjuvant 3-month hormonal therapy was administered. Primary endpoint was biochemical progression-free survival (BPFS) rate as defined by the Phoenix criteria. Secondary endpoints were cancer-specific survival (CSS), overall survival (OS), patient reported functional outcomes and complication rates. Factors influencing de BPFS were evaluated individually using Kaplan-Meyer and Cox regression models and in a multivariate model using Cox regression. RESULTS: During the mentioned period, a total of 177 men were treated with cryotherapy. With a mean follow-up of 60 months (SD 32.9), the Kaplan-Meier analysis shows an overall BPFS rate was 67%. BPFS by risk group was 70.2%, 70.3% and 50.0% for the low, intermediate and high risk groups, respectively (p = 0.925). Overall time to BR was 93.67 months (SD 2.84, IC95%: 88.10-99.24): 95.91 (SD 3,44), 93.23 (SD 4.81) and 89.77 (SD 6.67) months for the low, intermediate and high risk groups, respectively. In both univariate and multivariate analysis, the only predictor of biochemical progression was de PSA nadir (HR 1.56 IC95%: 1.50-1.63). Continence was fully maintained in 95% of patients after the procedure. Postoperative complications included UTI (17.5%), hematuria (9.6%), perineal hematoma (11%) and postoperative pain (4.5%). No fistulas were reported. 8.5% of patients had acute urinary retention solved conservatively. CONCLUSION: Cryotherapy is a safe option for selected patients with localized prostate cancer that provides competitive oncologic outcomes and a low morbidity profile.

Urine cytology suspicious for urothelial carcinoma: Prospective follow-up of cases using cytology and urine biomarker-based ancillary techniques.

BACKGROUND: Urine cytology results that are suspicious for urothelial carcinoma (UC) are challenging. The objective of this study was to elucidate the clinical significance of such results in patients who have a negative cystoscopy. METHODS: In this prospective study, 83 patients who had urine cytology that was suspicious of UC and a negative cystoscopy underwent a second cystoscopy and urine evaluation by cytology, UroVysion fluorescence in situ hybridization (FISH) assay, FGFR3 (fibroblast growth factor receptor 3) and TERT (telomerase reverse transcriptase) mutations and an 8-gene expression classifier (GEC). Results from all techniques were compared with patients' clinical outcomes. RESULTS: The presence of tumor was identified in 41% of patients; of these, 82% had tumors identified at their second evaluation (76% high-grade [HG] tumors), and 18% had tumors identified at a later follow-up (50% were HG tumors). After The Paris System for Reporting urinary Cytology (TPS) reclassification, 53 cytology results still had an indeterminate diagnosis (13 were suspicious for HGUC, and 40 had atypical urothelial cells (AUCs)]. Complete results from second evaluations using urine cytology, cytology-TPS, FISH, and GEC were available for 6 cases that were suspicious for HGUC and 34 cases that had AUCs. The sensitivity of these techniques to detect HG tumors in cases that were suspicious for HGUC was 100%, except for cytology-TPS, for which the sensitivity was 50%. The sensitivity of cytology and cytology-TPS to detect HG tumors in cases with AUCs was 33%, whereas the sensitivity of fluorescence in situ hybridization and GEC in these cases was 83% and 75%, respectively, to detect HG tumors at the second evaluation. CONCLUSIONS: The current results indicate the relevant clinical significance of indeterminate urine cytology findings and strongly suggest the use of complementary evaluations by urine biomarker-based, ancillary techniques to elucidate their significance.

Urine Gene Expression Profiles in Bladder Pain Syndrome Patients Treated with Triamcinolone.

BACKGROUND: The pathogenesis of bladder pain syndrome (BPS) remains incompletely defined, and there is no standard treatment for BPS as yet. OBJECTIVE: To gain detailed insight into the disease pathobiology of BPS through comparative gene expression analysis of urine from BPS patients versus control individuals and, furthermore, to determine the efficacy of triamcinolone treatment in BPS patients in terms of the gene expression profiles in urine. DESIGN, SETTING, AND PARTICIPANTS: A prospective pilot study including 21 urine samples from patients with Hunner's lesions (n=6) and controls (n=9) between January and August 2017. INTERVENTION: Triamcinolone treatment of BPS patients. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Urine samples from BPS patients were collected before (pretreatment group) and 2 wk after triamcinolone treatment (post-treatment group). Gene expression of urine sediment was analyzed using RNA sequencing. Pathways and biological processes in which differentially expressed genes are involved were analyzed. RESULTS AND LIMITATIONS: A total of 3745 genes were found to be differentially expressed between the three groups tested. Gene expression differences between controls and BPS samples (630 differentially expressed genes) were more pronounced than the differences between pre- and post-treatment BPS samples (197 differentially expressed genes). Gen Set Enrichment Analysis showed that differentially expressed genes in BPS patients (pretreatment), compared with controls, were enriched for some functional gene networks associated with several metabolic processes and ribosome biogenesis. The limited number of patients included may not accurately represent the BPS population. CONCLUSIONS: Gene expression profiles of urine sediment are able to discriminate between BPS and control patients. Moreover, we show that triamcinolone induces changes in urine gene expression profiles. PATIENT SUMMARY: In this report, we looked at gene expression profiles of urine sediment from patients with Hunner's lesions, before and after triamcinolone treatment, and control individuals. We found that urine gene expression profiles are able to discriminate Hunner's lesions patients from controls. Furthermore, we report, for the first time, that triamcinolone treatment of patients with Hunner's lesions induces changes in bladder gene expression profiles that can be observed in urine samples.

Paleopathology of soft tissues: what mummies can reveal.

Paleopathology is a science located in a crossroad between history, archaeology, anthropology, and medicine an can offer unique historical knowledge by using techniques of traditional pathology as well as other branches of Medicine, which is especially fruitful when applied to ancient subjects in which soft tissues are preserved: mummies.

Epidemiologic and economic burden of HPV diseases in Spain: implication of additional 5 types from the 9-valent vaccine.

BACKGROUND: A new nonavalent human papillomavirus (HPV) vaccine that includes genotypes 6/11/16/18/31/33/45/52/58 has been recently approved in Spain. A previous study has shown that attributable fraction of HPV related diseases in Spain is consistent with that reported in European and global studies. The aim of the present study was to estimate the annual direct costs associated to the following HPV-related diseases: genital warts, high grade precancerous lesions and cancer of cervix, vulva, vagina, anus and penis and head and neck cancer, caused by genotypes included in the nonavalent (9vHPV) and quadrivalent vaccines (4vHPV), in Spanish men and women. METHODS: Cancer registries and epidemiological studies were used to estimate the number of new annual cases of genital warts, anogenital precancerous lesions and cancer of cervix, vulva, vagina, anus, penis and head and neck, as well as the fraction attributable to HPV infection and to genotypes targeted by both vaccines in Spain. Costs per patient for each disease were obtained from the literature. In addition, 142 specialists were surveyed to estimate cost per patient of vulvar, vaginal, anal and penile precancerous lesions. The annual burden of diseases attributable to types targeted by both vaccines was estimated and compared. All results were validated by a panel of experts. RESULTS: In 2016, new genital warts, precancerous lesions and cancers attributable to types targeted by the 9vHPV were estimated at 49,251, 29,405 and 3381, respectively. Among them, 12,597 new precancerous lesions and 530 new cancers were related to the 5 additional types covered by the 9vHPV. Annual cost of new cases of these diseases associated to types targeted by the 4vHPV and 9vHPV were estimated at 116.7 and 150.9 million € for the Spanish National Health Service (NHS), respectively (2017 €). CONCLUSIONS: HPV-related diseases represent a major burden for the Spanish NHS. Annual new cases and costs related to the 5 additional types from the 9vHPV represent a significant burden compared with that associated to types included in the 4vHPV.

Persistent Borrelia Infection in Patients with Ongoing Symptoms of Lyme Disease.

INTRODUCTION: Lyme disease is a tickborne illness that generates controversy among medical providers and researchers. One of the key topics of debate is the existence of persistent infection with the Lyme spirochete, Borreliaburgdorferi, in patients who have been treated with recommended doses of antibiotics yet remain symptomatic. Persistent spirochetal infection despite antibiotic therapy has recently been demonstrated in non-human primates. We present evidence of persistent Borrelia infection despite antibiotic therapy in patients with ongoing Lyme disease symptoms. METHODS: In this pilot study, culture of body fluids and tissues was performed in a randomly selected group of 12 patients with persistent Lyme disease symptoms who had been treated or who were being treated with antibiotics. Cultures were also performed on a group of ten control subjects without Lyme disease. The cultures were subjected to corroborative microscopic, histopathological and molecular testing for Borrelia organisms in four independent laboratories in a blinded manner. RESULTS: Motile spirochetes identified histopathologically as Borrelia were detected in culture specimens, and these spirochetes were genetically identified as Borreliaburgdorferi by three distinct polymerase chain reaction (PCR)-based approaches. Spirochetes identified as Borrelia burgdorferi were cultured from the blood of seven subjects, from the genital secretions of ten subjects, and from a skin lesion of one subject. Cultures from control subjects without Lyme disease were negative for Borrelia using these methods. CONCLUSIONS: Using multiple corroborative detection methods, we showed that patients with persistent Lyme disease symptoms may have ongoing spirochetal infection despite antibiotic treatment, similar to findings in non-human primates. The optimal treatment for persistent Borrelia infection remains to be determined.

Human bocavirus 1 infection of CACO-2 cell line cultures.

Human bocavirus 1 (HBoV1) is a parvovirus associated with pneumonia in infants. It has been detected in different tissues, including colorectal tumors. In this study, we investigated whether Caco-2 cell line, derived from human colon cancer, can be utilized as a model for HBoV1 replication. We demonstrate HBoV1 replication in Caco-2 cultures supplemented with DEAE-dextran after inoculation with respiratory material from infected patients presenting with acute respiratory infection. A viral cycle of rapid development is displayed. However, in spite of HBoV1 DNA 4-fold increment in the supernatants and monolayers by day 1, evidencing that the system allows the virus genome replication after the entry occurred, infectious progeny particles were not produced. These results are consistent with an infection that is limited to a single growth cycle, which can be associated to mutations in the NS1 and VP1/VP2 regions of HBoV1 genome. Further research will contribute to fully elucidate these observations.

Pain relief after triamcinolone infiltration in patients with bladder pain syndrome with Hunner's ulcers.

INTRODUCTION AND HYPOTHESIS: Bladder pain syndrome (BPS) is a chronic condition with severe implications in the patient's quality of life with no definitive treatment. Our objective was to assess pain relief after triamcinolone injection in patients with BPS with Hunner's ulcers (HU). METHODS: Retrospective study of 20 consecutive patients with BPS treated at the Hospital Clinic of Barcelona with triamcinolone injection with flexible cystoscope between 2015 and 2016. Pain was assessed according to the visual analog scale (VAS) (0-10) before and after treatment. Outcomes were compared using Student's t test for paired samples. RESULTS: Twenty-seven procedures were performed in 20 patients, who were followed up for a median of 7 months (range 1-15). Median age was 75 years (52-86), and median time from diagnosis to treatment was 4.5 years (1-7). Fifteen (75 %) patients had received treatment with corticoid injection for BPS before entering the study. Pre- and postreatment VAS was 8 and 2.5 (p < 0.001), respectively. Pre -and postreatment VAS in those with muscular pain was 8 and 5 (p = 0.012), respectively and in those without muscular pain was 8 and 2 (p < 0.001), respectively. Three (15 %) patients required retreatment due to nonresponse and 5 (25 %) patients for pain recurrence after 4 months (3.5-8). Four of them (50 %) were performed with triamcinolone injection again. Seven of ten patients (70 %) followed for ≥8 months required at least one retreatment. CONCLUSION: Triamcinolone injection for HU in patients with BPS is associated with significant pain reduction. However, most patients will require retreatment.

Prior Lubrication of the Urethra Does Not Reduce Pain Perception in Men Undergoing Flexible Cystoscopy.

OBJECTIVE: The study aimed to test the hypothesis that the instillation of lidocaine gel does not reduce the pain related to flexible cystoscopy. MATERIAL AND METHODS: A prospective randomized study was designed to compare the pain perception between intraurethral instillation of lidocaine gel and saline solution in flexible cystoscopy. One hundred consecutive male patients attending for flexible cystoscopy were randomized to receive 10 ml of lidocaine gel or 10 ml of saline solution. Saline solution was also used for the irrigation pressure. Patients recorded their pain on a 10 cm Visual Analog Scale before and after the procedure. Patients also assessed whether the cystoscopy was more painful than the previous one. Statistical comparison was made using the t test for parametrical data and the Mann-Whitney U test for non-parametrical data. RESULTS: Mean pain score in the lidocaine group was 0.67 ± 1.11 cm (range 0-5) compared to 0.55 ± 1.10 cm (range 0-5) in the saline solution group. Pain perception did not differ significantly between the 2 groups (mean difference 0.12 cm, 95% CI -0.32 to 0.55, p = 0.40). CONCLUSIONS: Prior lubrication of the urethra does not reduce the pain produced during flexible cystoscopy. The introduction of flexible cystoscopes under direct vision and with an irrigation pressure might guarantee sufficient comfort and the lubricant gel instillation could be avoided.

Exploring the association between Morgellons disease and Lyme disease: identification of Borrelia burgdorferi in Morgellons disease patients.

BACKGROUND: Morgellons disease (MD) is a complex skin disorder characterized by ulcerating lesions that have protruding or embedded filaments. Many clinicians refer to this condition as delusional parasitosis or delusional infestation and consider the filaments to be introduced textile fibers. In contrast, recent studies indicate that MD is a true somatic illness associated with tickborne infection, that the filaments are keratin and collagen in composition and that they result from proliferation and activation of keratinocytes and fibroblasts in the skin. Previously, spirochetes have been detected in the dermatological specimens from four MD patients, thus providing evidence of an infectious process. METHODS & RESULTS: Based on culture, histology, immunohistochemistry, electron microscopy and molecular testing, we present corroborating evidence of spirochetal infection in a larger group of 25 MD patients. Irrespective of Lyme serological reactivity, all patients in our study group demonstrated histological evidence of epithelial spirochetal infection. Strength of evidence based on other testing varied among patients. Spirochetes identified as Borrelia strains by polymerase chain reaction (PCR) and/or in-situ DNA hybridization were detected in 24/25 of our study patients. Skin cultures containing Borrelia spirochetes were obtained from four patients, thus demonstrating that the organisms present in dermatological specimens were viable. Spirochetes identified by PCR as Borrelia burgdorferi were cultured from blood in seven patients and from vaginal secretions in three patients, demonstrating systemic infection. Based on these observations, a clinical classification system for MD is proposed. CONCLUSIONS: Our study using multiple detection methods confirms that MD is a true somatic illness associated with Borrelia spirochetes that cause Lyme disease. Further studies are needed to determine the optimal treatment for this spirochete-associated dermopathy.