Consistency between POLARS and LARS scores regarding the incidence of low anterior resection syndrome in a Chilean population undergoing rectal surgery secondary to cancer in a high-volume hospital.

AIM: The aim of this work was to evaluate the concordance between the low anterior resection syndrome (LARS) and preoperative LARS (POLARS) scores regarding the incidence of LARS in a Chilean population undergoing rectal surgery for cancer in a high-volume hospital. METHOD: The LARS score questionnaire, following telephone requests, was used to determine the presence and severity of LARS. The POLARS score was calculated based on variables described previously. Correlations and qualitative and quantitative concordance were evaluated using Spearman's correlation coefficient, the kappa coefficient and the Bland-Altman plot with Lin's concordance correlation coefficient. RESULTS: A total of 120 patients met the inclusion criteria: 37.5% underwent neoadjuvant radiotherapy, 61% underwent total mesorectal excision (TME) and 51.6% underwent ostomy. A total of 49% of patients did not present with LARS, whereas 28% had major LARS. The correlation between scales was poor, with a fair qualitative concordance to determine the presence/absence of LARS and a slight qualitative concordance to determine the degree of the intensity. The quantitative concordance was poor. CONCLUSION: In the Chilean population, concordance between the LARS and POLARS scores was qualitatively fair to determine the presence/absence of the disease and qualitatively slight to determine the degree of intensity. We do not suggest using the POLARS score in the perioperative period in the Chilean population deliberately, as the score may help to determine the presence/absence of LARS but cannot determine its degree of intensity. Additional evaluations are required to determine the factors contributing to the degree of agreement between the scales.

Using SWATH-MS to identify new molecular biomarkers in gingival crevicular fluid for detecting periodontitis and its response to treatment.

AIM: To identify new biomarkers to detect untreated and treated periodontitis in gingival crevicular fluid (GCF) using sequential window acquisition of all theoretical mass spectra (SWATH-MS). MATERIALS AND METHODS: GCF samples were collected from 44 periodontally healthy subjects and 40 with periodontitis (Stages III-IV). In the latter, 25 improved clinically 2 months after treatment. Samples were analysed using SWATH-MS, and proteins were identified by the UniProt human-specific database. The diagnostic capability of the proteins was determined with generalized additive models to distinguish the three clinical conditions. RESULTS: In the untreated periodontitis vs. periodontal health modelling, five proteins showed excellent or good bias-corrected (bc)-sensitivity/bc-specificity values of >80%. These were GAPDH, ZG16B, carbonic anhydrase 1, plasma protease inhibitor C1 and haemoglobin subunit beta. GAPDH with MMP-9, MMP-8, zinc-α-2-glycoprotein and neutrophil gelatinase-associated lipocalin and ZG16B with cornulin provided increased bc-sensitivity/bc-specificity of >95%. For distinguishing treated periodontitis vs. periodontal health, most of these proteins and their combinations revealed a predictive ability similar to previous modelling. No model obtained relevant results to differentiate between periodontitis conditions. CONCLUSIONS: New single and dual GCF protein biomarkers showed outstanding results in discriminating untreated and treated periodontitis from periodontal health. Periodontitis conditions were indistinguishable. Future research must validate these findings.

Are farmers motivated to select for heat tolerance? Linking attitudinal factors, perceived climate change impacts, and social trust to farmers' breeding desires.

This study provides an understanding of dairy farmers' willingness to include heat tolerance in breeding goals and the modulating effect of sociopsychological factors and farm profile. A survey instrument including a choice experiment was designed to specifically address the trade-off between heat tolerance and milk production level. A total of 122 farmers across cattle, goat, and sheep farms were surveyed face-to-face. The results of the experiment show that most farmers perceive that heat stress and climate change are increasingly important problems, and that farming communities should invest more in generating knowledge and resources on mitigation strategies. However, we found limited initial support for selection for heat tolerance. This attitude changed when farmers were presented with objective information on the benefits and limitations of the different breeding choices, after which most farmers supported selection for heat tolerance, but only if doing so would compromise milk production gains to a small extent. Our results show that farmers' selection choices are driven by the interactions between heat stress risk perception, attitudes toward breeding tools, social trust, the species reared, and farm production level. In general, farmers willing to support selection of heat-tolerant animals are those with positive attitudes toward genetic values and genomic information and a strong perception of climate change and heat stress impacts on farms. On the contrary, negative support for selection for heat tolerance is found among farmers with high milk production levels; high trust in farming magazines, livestock farmers' associations, and veterinarians; and low trust in environmental and animalist groups.

Systematic review on the impact of exercise on intraocular pressure in glaucoma patients.

Due to limited studies, we systematically reviewed evidence on the impact of physical exercise on intraocular pressure (IOP) in glaucoma patients, adhering to PRISMA guidelines. Using MEDLINE/Web of Science, PubMed, and Scopus, we selected English, Portuguese, or Spanish studies excluding case reports and yoga-based interventions. From 1001 records, 15 studies were independently evaluated. Evaluated through the MMAT scoring system, two quantitative randomised controlled studies scored 100% while 13 non-randomised studies averaged 84.62%. Our findings indicated that both aerobic and resistance training led to an immediate IOP reduction post-exercise. However, these findings were largely from single-session experiments. In contrast, the effects of longer-term exercise programmes on IOP varied. Although our review underscores the potential utility of exercise in IOP management, the evidence remains inconclusive due to variations in study design, participant demographics, and exercise parameters. This lack of consistency in the research highlights the necessity for larger, standardised, and longer-term studies to robustly corroborate these preliminary findings.

Decreased expression of surfactant Protein-C and CD74 in alveolar epithelial cells during influenza virus A(H1N1)pdm09 and H3N2 infection.

The primary replication site of Influenza A virus (IAV) is type II alveolar epithelial cells (AECII), which are central to normal lung function and present important immune functions. Surfactant components are synthesized primarily by AECII, which play a crucial role in host defense against infection. The aim of this study was to analyze if the impact of influenza infection is differential between A(H1N1)pdm09 and A/Victoria/3/75 (H3N2) on costimulatory molecules and ProSP-C expression in AECII from BALB/c mice infected and A549 cell line infected with both strains. Pandemic A(H1N1)pdm09 and A/Victoria/3/75 (H3N2) were used to infect BALB/c mice and the A549 cell line. We evaluated the surface expression of co-stimulatory molecules (CD45/CD31/CD74/ProSP-C) in AECII and A549 cell lines. Our results showed a significant decrease in ProSP-C+ CD31- CD45- and CD74+ CD31- CD45- expression in AECII and A549 cell line with the virus strain A(H1N1)pdm09 versus A/Victoria/3/75 (H3N2) and controls (non-infection conditions). Our findings indicate that changes in the expression of ProSP-C in AECII and A549 cell lines in infection conditions could result in dysfunction leading to decreased lung compliance, increased work of breathing and increased susceptibility to injury.

Accuracy of periodontitis diagnosis obtained using multiple molecular biomarkers in oral fluids: A systematic review and meta-analysis.

AIM: To determine the accuracy of biomarker combinations in gingival crevicular fluid (GCF) and saliva through meta-analysis to diagnose periodontitis in systemically healthy subjects. METHODS: Studies on combining two or more biomarkers providing a binary classification table, sensitivity/specificity values or group sizes in subjects diagnosed with periodontitis were included. The search was performed in August 2022 through PUBMED, EMBASE, Cochrane, LILACS, SCOPUS and Web of Science. The methodological quality of the articles selected was evaluated using the QUADAS-2 checklist. Hierarchical summary receiver operating characteristic modelling was employed to perform the meta-analyses (CRD42020175021). RESULTS: Twenty-one combinations in GCF and 47 in saliva were evaluated. Meta-analyses were possible for six salivary combinations (median sensitivity/specificity values): IL-6 with MMP-8 (86.2%/80.5%); IL-1ß with IL-6 (83.0%/83.7%); IL-1ß with MMP-8 (82.7%/80.8%); MIP-1α with MMP-8 (71.0%/75.6%); IL-1ß, IL-6 and MMP-8 (81.8%/84.3%); and IL-1ß, IL-6, MIP-1α and MMP-8 (76.6%/79.7%). CONCLUSIONS: Two-biomarker combinations in oral fluids show high diagnostic accuracy for periodontitis, which is not substantially improved by incorporating more biomarkers. In saliva, the dual combinations of IL-1ß, IL-6 and MMP-8 have an excellent ability to detect periodontitis and a good capacity to detect non-periodontitis. Because of the limited number of biomarker combinations evaluated, further research is required to corroborate these observations.

Short-term anti-plaque effect of a cymenol mouthwash analysed using the DenTiUS Deep Plaque software: a randomised clinical trial.

BACKGROUND: The effect of cymenol mouthwashes on levels of dental plaque has not been evaluated thus far. OBJECTIVE: To analyse the short-term, in situ, anti-plaque effect of a 0.1% cymenol mouthwash using the DenTiUS Deep Plaque software. METHODS: Fifty orally healthy participants were distributed randomly into two groups: 24 received a cymenol mouthwash for eight days (test group A) and 26 a placebo mouthwash for four days and a cymenol mouthwash for a further four days thereafter (test group B). They were instructed not to perform other oral hygiene measures. On days 0, 4, and 8 of the experiment, a rinsing protocol for staining the dental plaque with sodium fluorescein was performed. Three intraoral photographs were taken per subject under ultraviolet light. The 504 images were analysed using the DenTiUS Deep Plaque software, and visible and total plaque indices were calculated (ClinicalTrials ID NCT05521230). RESULTS: On day 4, the percentage area of visible plaque was significantly lower in test group A than in test group B (absolute = 35.31 ± 14.93% vs. 46.57 ± 18.92%, p = 0.023; relative = 29.80 ± 13.97% vs. 40.53 ± 18.48%, p = 0.024). In comparison with the placebo, the cymenol mouthwash was found to have reduced the growth rate of the area of visible plaque in the first four days by 26% (absolute) to 28% (relative). On day 8, the percentage areas of both the visible and total plaque were significantly lower in test group A than in test group B (visible absolute = 44.79 ± 15.77% vs. 65.12 ± 16.37%, p < 0.001; visible relative = 39.27 ± 14.33% vs. 59.24 ± 16.90%, p < 0.001; total = 65.17 ± 9.73% vs. 74.52 ± 13.55%, p = 0.007). Accounting for the growth rate with the placebo mouthwash on day 4, the above results imply that the cymenol mouthwash in the last four days of the trial reduced the growth rate of the area of visible plaque (absolute and relative) by 53% (test group A) and 29% (test group B), and of the area of total plaque by 48% (test group A) and 41% (test group B). CONCLUSIONS: The 0.1% cymenol mouthwash has a short-term anti-plaque effect in situ, strongly conditioning the rate of plaque growth, even in clinical situations with high levels of dental plaque accumulation.

Risk factors for melanoma by anatomical site: an evaluation of aetiological heterogeneity.

BACKGROUND: Melanoma aetiology has been proposed to have two pathways, which are determined by naevi and type of sun exposure and related to the anatomical site where melanoma develops. OBJECTIVES: We examined associations with melanoma by anatomical site for a comprehensive set of risk factors including pigmentary and naevus phenotypes, ultraviolet radiation exposure and polygenic risk. METHODS: We analysed harmonized data from 2617 people with incident first invasive melanoma and 975 healthy controls recruited through two population-based case-control studies in Australia and the UK. Questionnaire data were collected by interview using a single protocol, and pathway-specific polygenic risk scores were derived from DNA samples. We estimated adjusted odds ratios using unconditional logistic regression that compared melanoma cases at each anatomical site with all controls. RESULTS: When cases were compared with control participants, there were stronger associations for many naevi vs. no naevi for melanomas on the trunk, and upper and lower limbs than on the head and neck (P-heterogeneity < 0·001). Very fair skin (vs. olive/brown skin) was more weakly related to melanoma on the trunk than to melanomas at other sites (P-heterogeneity = 0·04). There was no significant difference by anatomical site for polygenic risk. Increased weekday sun exposure was positively associated with melanoma on the head and neck but not on other sites. CONCLUSIONS: We found evidence of aetiological heterogeneity for melanoma, supporting the dual pathway hypothesis. These findings enhance understanding of risk factors for melanoma and can guide prevention and skin examination education and practices.

Timing of HPV16-E6 antibody seroconversion before OPSCC: findings from the HPVC3 consortium.

BACKGROUND: Human papillomavirus type 16 (HPV16)-E6 antibodies are detectable in peripheral blood before diagnosis in the majority of HPV16-driven oropharyngeal squamous cell carcinoma (OPSCC), but the timing of seroconversion is unknown. PATIENTS AND METHODS: We formed the HPV Cancer Cohort Consortium which comprises nine population cohorts from Europe, North America and Australia. In total, 743 incident OPSCC cases and 5814 controls provided at least one pre-diagnostic blood sample, including 111 cases with multiple samples. Median time between first blood collection and OPSCC diagnosis was 11.4 years (IQR = 6-11 years, range = 0-40 years). Antibodies against HPV16-E6 were measured by multiplex serology (GST fusion protein based Luminex assay). RESULTS: HPV16-E6 seropositivity was present in 0.4% of controls (22/5814; 95% CI 0.2% to 0.6%) and 26.2% (195/743; 95% CI 23.1% to 29.6%) of OPSCC cases. HPV16-E6 seropositivity increased the odds of OPSCC 98.2-fold (95% CI 62.1-155.4) in whites and 17.2-fold (95% CI 1.7-170.5) in blacks. Seropositivity in cases was more frequent in recent calendar periods, ranging from 21.9% pre-1996 to 68.4% in 2005 onwards, in those with blood collection near diagnosis (lead time <5 years). HPV16-E6 seropositivity increased with lead time: 0.0%, 13.5%, 23.7%, and 38.9% with lead times of >30 years (N = 24), 20-30 years (N = 148), 10-20 years (N = 228), and <10 years (N = 301 cases) (p-trend < 0.001). Of the 47 HPV16-E6 seropositive cases with serially-collected blood samples, 17 cases seroconverted during follow-up, with timing ranging from 6 to 28 years before diagnosis. For the remaining 30 cases, robust seropositivity was observed up to 25 years before diagnosis. CONCLUSIONS: The immune response to HPV16-driven tumorigenesis is most often detectable several decades before OPSCC diagnosis. HPV16-E6 seropositive individuals face increased risk of OPSCC over several decades.

Correction to: X-linked hypophosphatemia and growth.

The authors of the article would like to note an error in the acknowledgements section of this paper.

Diagnostic exome sequencing in children: A survey of parental understanding, experience and psychological impact.

Clinical exome sequencing (CES) is increasingly being used as an effective diagnostic tool in the field of pediatric genetics. We sought to evaluate the parental experience, understanding and psychological impact of CES by conducting a survey study of English-speaking parents of children who had diagnostic CES. Parents of 192 unique patients participated. The parent's interpretation of the child's result agreed with the clinician's interpretation in 79% of cases, with more frequent discordance when the clinician's interpretation was uncertain. The majority (79%) reported no regret with the decision to have CES. Most (65%) reported complete satisfaction with the genetic counseling experience, and satisfaction was positively associated with years of genetic counselor (GC) experience. The psychological impact of CES was greatest for parents of children with positive results and for parents with anxiety or depression. The results of this study are important for helping clinicians to prepare families for the possible results and variable psychological impact of CES. The frequency of parental misinterpretation of test results indicates the need for additional clarity in the communication of results. Finally, while the majority of patients were satisfied with their genetic counseling, satisfaction was lower for new GCs, suggesting a need for targeted GC training for genomic testing.

A novel anaerobic filter membrane bioreactor: prototype start-up and filtration assays.

Anaerobic digestion allows efficient treatment of high loaded wastewater, and membrane technology allows obtaining high quality effluents with complete biomass retention. However, high biomass concentration interferes with membrane fouling. In the present work, a new bioreactor that integrates an attached biomass anaerobic culture on a fixed bed and a submerged membrane has been started up. The recirculation between the digestion and filtration chambers is coupled to the gas-lift effect of the bubbling employed for the scouring of the membranes, avoiding the use or electromechanical pumps that damage the suspended biomass. The support material retains the biomass in the digestion tank despite the downwards flow, avoiding the submerged membrane contacting with a high concentrated suspension. This novel system, called an anaerobic filter membrane bioreactor was immediately started up, achieving chemical oxygen demand (COD) removal efficiencies of 96% at an organic loading rate (OLR) of 7 kg COD/m3·d. In order to select filtration flux, specific gas demand and filtration cycle duration, the results of 15 short term assays, eight hours for each one, is presented for fluxes between 15.7 and 17.7 L/m2·h, cycle duration between 10 and 30 minutes, and three levels of scouring. It was checked that reversible and irreversible fouling were directly related when dTMP/dt > 2.5 mbar/min.

Restricted co-localization of glutamate and dopamine in neurons of the adult sea lamprey brain.

Co-localization of dopamine with other classical neurotransmitters in the same neuron is a common phenomenon in the brain of vertebrates. In mammals, some dopaminergic neurons of the ventral tegmental area and the hypothalamus have a glutamatergic co-phenotype. However, information on the presence of this type of dopaminergic neurons in other vertebrate groups is very scant. Here, we aimed to provide new insights on the evolution of this neuronal co-phenotype by studying the presence of a dual dopaminergic/glutamatergic neuron phenotype in the central nervous system of lampreys. Double immunofluorescence experiments for dopamine and glutamate in adult sea lampreys revealed co-localization of both neurotransmitters in some neurons of the preoptic nucleus, the nucleus of the postoptic commissure, the dorsal hypothalamus and in cerebrospinal fluid-contacting cells of the caudal rhombencephalon and rostral spinal cord. Moreover, co-localization of dopamine and glutamate was found in dopaminergic fibres in a few brain regions including the lateral pallium, striatum, and the preoptic and postoptic areas but not in the brainstem. Our results suggest that the presence of neurons with a dopaminergic/glutamatergic co-phenotype is a primitive character shared by jawless and jawed vertebrates. However, important differences in the distribution of these neurons and fibres were noted among the few vertebrates investigated to date. This study offers an anatomical basis for further work on the role of glutamate in dopaminergic neurons.

X-linked hypophosphatemia and growth.

X-Linked hypophosphatemia (XLH) is the most common form of hereditary rickets caused by loss-of function mutations in the PHEX gene. XLH is characterized by hypophosphatemia secondary to renal phosphate wasting, inappropriately low concentrations of 1,25 dihydroxyvitamin D and high circulating levels of fibroblast growth factor 23 (FGF23). Short stature and rachitic osseous lesions are characteristic phenotypic findings of XLH although the severity of these manifestations is highly variable among patients. The degree of growth impairment is not dependent on the magnitude of hypophosphatemia or the extent of legs´ bowing and height is not normalized by chronic administration of phosphate supplements and 1α hydroxyvitamin D derivatives. Treatment with growth hormone accelerates longitudinal growth rate but there is still controversy regarding the potential risk of increasing bone deformities and body disproportion. Treatments aimed at blocking FGF23 action are promising, but information is lacking on the consequences of counteracting FGF23 during the growing period. This review summarizes current knowledge on phosphorus metabolism in XLH, presents updated information on XLH and growth, including the effects of FGF23 on epiphyseal growth plate of the Hyp mouse, an animal model of the disease, and discusses growth hormone and novel FGF23 related therapies.

Plasmapheresis and other extracorporeal filtration techniques in critical patients.

Plasmapheresis is an extracorporeal technique that eliminates macromolecules involved in pathological processes from plasma. A review is made of the technical aspects, main indications in critical care and potential complications of plasmapheresis, as well as of other extracorporeal filtration techniques such as endotoxin-removal columns and other devices designed to eliminate cytokines or modulate the inflammatory immune response in critical patients.

Replication of PTPRC as genetic biomarker of response to TNF inhibitors in patients with rheumatoid arthritis.

Genetic biomarkers could be useful for orienting treatment of patients with rheumatoid arthritis (RA), but none has been convincingly validated yet. Putative biomarkers include 14 single nucleotide polymorphisms that have shown association with response to TNF inhibitors (TNFi) in candidate gene studies and that we assayed here in 755 RA patients. Three of them, in the PTPRC, IL10 and CHUK genes, were significantly associated with response to TNFi. The most significant result was obtained with rs10919563 in PTPRC, which is a confirmed RA susceptibility locus. Its RA risk allele was associated with improved response (B=0.33, P=0.006). This is the second independent replication of this biomarker (P=9.08 × 10(-8) in the combined 3003 RA patients). In this way, PTPRC has become the most replicated genetic biomarker of response to TNFi. In addition, the positive but weaker replication of IL10 and CHUK should stimulate further validation studies.

Management of agricultural soils for greenhouse gas mitigation: Learning from a case study in NE Spain.

A portfolio of agricultural practices is now available that can contribute to reaching European mitigation targets. Among them, the management of agricultural soils has a large potential for reducing GHG emissions or sequestering carbon. Many of the practices are based on well tested agronomic and technical know-how, with proven benefits for farmers and the environment. A suite of practices has to be used since none of the practices can provide a unique solution. However, there are limitations in the process of policy development: (a) agricultural activities are based on biological processes and thus, these practices are location specific and climate, soils and crops determine their agronomic potential; (b) since agriculture sustains rural communities, the costs and potential for implementation have also to be regionally evaluated and (c) the aggregated regional potential of the combination of practices has to be defined in order to inform abatement targets. We believe that, when implementing mitigation practices, three questions are important: Are they cost-effective for farmers? Do they reduce GHG emissions? What policies favour their implementation? This study addressed these questions in three sequential steps. First, mapping the use of representative soil management practices in the European regions to provide a spatial context to upscale the local results. Second, using a Marginal Abatement Cost Curve (MACC) in a Mediterranean case study (NE Spain) for ranking soil management practices in terms of their cost-effectiveness. Finally, using a wedge approach of the practices as a complementary tool to link science to mitigation policy. A set of soil management practices was found to be financially attractive for Mediterranean farmers, which in turn could achieve significant abatements (e.g., 1.34 MtCO2e in the case study region). The quantitative analysis was completed by a discussion of potential farming and policy choices to shape realistic mitigation policy at European regional level.

Newborn screening for X-linked adrenoleukodystrophy in New York State: diagnostic protocol, surveillance protocol and treatment guidelines.

PURPOSE: To describe a diagnostic protocol, surveillance and treatment guidelines, genetic counseling considerations and long-term follow-up data elements developed in preparation for X-linked adrenoleukodystrophy (X-ALD) newborn screening in New York State. METHODS: A group including the director from each regional NYS inherited metabolic disorder center, personnel from the NYS Newborn Screening Program, and others prepared a follow-up plan for X-ALD NBS. Over the months preceding the start of screening, a series of conference calls took place to develop and refine a complete newborn screening system from initial positive screen results to long-term follow-up. RESULTS: A diagnostic protocol was developed to determine for each newborn with a positive screen whether the final diagnosis is X-ALD, carrier of X-ALD, Zellweger spectrum disorder, acyl CoA oxidase deficiency or D-bifunctional protein deficiency. For asymptomatic males with X-ALD, surveillance protocols were developed for use at the time of diagnosis, during childhood and during adulthood. Considerations for timing of treatment of adrenal and cerebral disease were developed. CONCLUSION: Because New York was the first newborn screening laboratory to include X-ALD on its panel, and symptoms may not develop for years, long-term follow-up is needed to evaluate the presented guidelines.

Trends on epidemiological, virological, and clinical features among newly diagnosed HIV-1 persons in Northwest Spain over the last 10 years.

To describe temporal trend and characteristics of newly HIV-diagnosed patients in a medical care area in Northwest Spain over the last 10 years. All newly diagnosed patients for HIV-infection from 2004 to 2013 at a reference medical care area in Northwest of Spain were identified. Epidemiological, virological, immunological, and clinical data, as well as HIV genotype and drug resistance information were recorded. A total of 565 newly HIV-diagnosed patients were identified. The number of new cases increased in the last 5 years (66 cases/year). Overall, 53.1% had a median CD4 counts < 350 cells/µl and 33.6% had an AIDS defining criteria. Non-B variants were found in 34.4% of patients being subtype F (25.8%) the most common non-B subtype. The rate of transmitted drug resistance (TDR) over the study period was 3.7%, but a decreased to 2.6% was observed in the last 5 years. The most prevalent TDR mutations were: T215 revertants (1.5%), K219QENR (1.2%), for NRTIs; K103N (1.9%), for NNRTIs; L90M (0.3%), for PIs. Overall, 73.2% of patients started antiretroviral treatment and 9.9% of patients died during follow-up. The number of newly HIV diagnosed patients increased since year 2009. There is a high prevalence of late diagnosis (53%) and 33% had an AIDS defining criteria. Interestingly, the most prevalent non-B subtype in our population was F (25.8%). These findings support the need to facilitate the access for HIV testing to reduce the rate of late HIV diagnosis, improve the clinical outcome and prevent HIV transmission.

Impact of HIV infection on sustained virological response to treatment against hepatitis C virus with pegylated interferon plus ribavirin.

It is commonly accepted that human immunodeficiency (HIV) coinfection negatively impacts on the rates of sustained virological response (SVR) to therapy with pegylated interferon plus ribavirin (PR). However, this hypothesis is derived from comparing different studies. The aim of this study was to determine the impact of HIV coinfection on SVR to PR in one single population. In a multicentric, prospective study conducted between 2000 and 2013, all previously naïve hepatitis C virus (HCV)-infected patients who started PR in five Spanish hospitals were analyzed. SVR was evaluated 24 weeks after the scheduled end of therapy. Of the 1046 patients included in this study, 413 (39%) were coinfected with HIV. Three hundred and forty-one (54%) HCV-monoinfected versus 174 (42%) HIV/HCV-coinfected patients achieved SVR (p < 0.001). The corresponding figures for undetectable HCV RNA at treatment week 4 were 86/181 (47%) versus 59/197 (30%), p < 0.001. SVR was observed in 149 (69%) HCV genotype 2/3-monoinfected subjects versus 91 (68%) HIV/HCV genotype 2/3-coinfected subjects (p = 0.785). In the HCV genotype 1/4-infected population, 188 (46%) monoinfected patients versus 82 (30%) with HIV coinfection (p < 0.001) achieved SVR. In this subgroup, absence of HIV coinfection was independently associated with higher SVR [adjusted odds ratio (95% confidence interval): 2.127 (1.135-3.988); p = 0.019] in a multivariate analysis adjusted for age, sex, baseline HCV RNA load, IL28B genotype, fibrosis stage, and type of pegylated interferon. HIV coinfection impacts on the rates of SVR to PR only in HCV genotype 1/4-infected patients, while it has no effect on SVR in the HCV genotype 2/3-infected subpopulation.