Skin lesions in neurofibromatosis type 2: diagnostic and prognostic significance of cutaneous (plexiform) schwannomas.

BACKGROUND: Neurofibromatosis type 2 (NF2) is a genetic disease characterized by the appearance of multiple tumours in the nervous system. Cutaneous lesions are common and may provide useful diagnostic and prognostic information, but they have not been widely studied. OBJECTIVES: To characterize cutaneous lesions in a Spanish cohort of patients with NF2 and investigate associations with clinical and genetic severity. METHODS: We studied the clinical and histologic characteristics of cutaneous lesions in 49 patients with NF2 and analysed correlations with phenotype- and genotype-based severity scores. We collected information on the presence/absence of cutaneous lesions, location, age at onset, type of lesion, and histologic features. We also studied level of systemic involvement and genetic mutations involved. RESULTS: Forty-nine patients (31 women [63.3%] and 18 men [36.7%]) were analysed, and 33 (67.3%) had cutaneous lesions presumed to be schwannomas. According to their clinical form, they were distributed as follows: 24 patients (48%) had deep tumours, 21 (42%) had plaque-like lesions, and 3 (6%) had superficial tumours. Histologic examination from 27 lesions analysed out 23 patients showed classic schwannoma or hybrid schwannoma-neurofibroma features in the 8 deep tumours biopsied and plexiform schwannoma features in the 17 plaque-like lesions and the 2 superficial tumours analysed. Early onset (first 2 decades of life) was reported by all patients with plaques and superficial tumours. In our cohort, 100% of the patients with plaque-like lesions and superficial tumours with microscopic features of plexiform schwannoma were in the 2 groups with the most severe clinical phenotypes, and 82.6% of them were in the 3 most severe genotype-based classes. CONCLUSIONS AND RELEVANCE: Cutaneous lesions, specially plexiform schwannomas, are common in NF2, and they usually appear at an early age providing useful diagnostic and prognostic information. These tumours are part of the spectrum of cutaneous manifestations in this disease. Although its diagnostic and prognostic value has been pointed out, there are few studies focussed on their analysis.

Protocol for assessing mortality reduction with the early use of noninvasive ventilation in prehospital emergency services: A multicentre, observational cohort study in Madrid, Spain.

BACKGROUND: Acute respiratory failure (ARF) has become one of the most prevalent serious pathologies encountered in the emergency medical service (EMS). In hospital settings, noninvasive ventilation (NIV) therapy prevents complications from more aggressive treatments for that condition. However, the scarce evidence on the benefits of NIV in prehospital EMS (i.e., during transport to the hospital) is inconclusive. OBJECTIVES: To determine whether the administration of NIV during prehospital EMS in cases of ARF reduces in-hospital mortality compared with starting NIV on arrival to in-patient EMS. METHODS: This is a multicentre, observational, prospective cohort study. We recruited a total of 317 patients from the Madrid region (Spain) who were prescribed NIV for their ARF using a nonprobabilistic consecutive sampling method. Analyses of the main outcome (in-hospital mortality) and secondary outcomes (length of hospital stay, readmissions, percentage of intensive care unit admissions, and cost-effectiveness) will include descriptive analyses of patients' characteristics, as well as bivariate and multivariate analyses and cost-effectiveness analysis. DISCUSSION: This study will provide data on NIV management in prehospital and in-patient EMS in patients with ARF. Results will contribute to the existing evidence on the benefits of NIV in the context of prehospital EMS while underlining the importance of a standardized formal training for physicians and nurses working in prehospital and in-patient EMSs. CONCLUSION: The VentilaMadrid study will provide valuable data on the clinical factors of patients receiving NIV in prehospital EMS. Further, were our hypothesis to be confirmed, our results would strongly suggest that the administration of NIV in prehospital EMS by medical and nursing profesionals formally trained in the technique reduces mortality and improves prognoses.

SARS-CoV-2 contact tracing among disadvantaged populations during epidemic intervals should be a priority strategy: results from a pilot experiment in Barcelona.

OBJECTIVES: The aim of this study was to trace contacts of coronavirus disease 2019 (COVID-19) hospitalised patients and determine the risk factors of infection in urban areas. STUDY DESIGN: Longitudinal analysis of contacts identified from index cases. METHODS: A contact tracing study was carried out in the Northern Metropolitan area of Barcelona, Spain, during the inter-epidemic lapse of May to July 2020, a period of low SARS-CoV-2 incidence. Index cases were notified from the referral hospital. Contacts were traced and followed up for 14 days. Reverse transcription polymerase chain reaction was performed on day 0 and day 14 for contacts. RESULTS: In total, 368 contacts were identified from 81 index cases (median of seven contacts per index case), from which 308 were traced successfully. The median age of contacts was 28 years, 62% (223 of 368) were men. During the follow-up period, 100 contacts tested positive for COVID-19 (32.5% [95% confidence interval {CI} = 27.3-38.0]), with a secondary infection rate of 48.3% (95% CI = 40.8-55.9) among housemates. Clusters of index and respective contacts tended to aggregate within disadvantaged neighbourhoods (P < 0.001), and non-national index cases (N = 28, 34.1%) resulted in higher secondary infection rates compared with nationals (51.0% [95% CI = 41.0-60.9] vs 22.3% [95% CI = 16.8-28.8]; P < 0.001). CONCLUSIONS: Disadvantaged communities experience a disproportionate burden of COVID-19 and may act as infection reservoirs. Contact tracing with a cross-cutting approach among these communities is required, especially during inter-epidemic periods.

Three-dimensional regional bi-ventricular shape remodeling is associated with exercise capacity in endurance athletes.

AIMS: Endurance athletes develop cardiac remodeling to cope with increased cardiac output during exercise. This remodeling is both anatomical and functional and shows large interindividual variability. In this study, we quantify local geometric ventricular remodeling related to long-standing endurance training and assess its relationship with cardiovascular performance during exercise. METHODS: We extracted 3D models of the biventricular shape from end-diastolic cine magnetic resonance images acquired from a cohort of 89 triathlon athletes and 77 healthy sedentary subjects. Additionally, the athletes underwent cardio-pulmonary exercise testing, together with an echocardiographic study at baseline and few minutes after maximal exercise. We used statistical shape analysis to identify regional bi-ventricular shape differences between athletes and non-athletes. RESULTS: The ventricular shape was significantly different between athletes and controls (p < 1e-6). The observed regional remodeling in the right heart was mainly a shift of the right ventricle (RV) volume distribution towards the right ventricular infundibulum, increasing the overall right ventricular volume. In the left heart, there was an increment of left ventricular mass and a dilation of the left ventricle. Within athletes, the amount of such remodeling was independently associated to higher peak oxygen pulse (p < 0.001) and weakly with greater post-exercise RV free wall longitudinal strain (p = 0.03). CONCLUSIONS: We were able to identify specific bi-ventricular regional remodeling induced by long-lasting endurance training. The amount of remodeling was associated with better cardiopulmonary performance during an exercise test.

Effectiveness of salivary stimulation using xylitol-malic acid tablets as coadjuvant treatment in patients with gastro-oesophageal reflux disease: early findings.

BACKGROUND: Besides dental erosion syndrome, other oral syndromes could benefit from the stimulation of salivary secretion, in patients with gastro-oesophageal reflux disease (GORD). Our aims is evaluate the improvement of oral extra-oesophageal manifestations in patients with GORD using xylitol-malic acid tablets to stimulate salivary secretion. MATERIAL AND METHODS: The effectiveness of salivary stimulation using xylitol-malic acid tablets (as a supplement to omeprazole 40 mg/day) was assessed in a clinical trial (n = 14) lasting six months with patients with prior positive pH-metry, through GORD extra-oesophageal clinical signs, GerdQ and RDQ questionnaires, odontological variables, basal salivary secretion, stimulated salivary secretion, pH and buffer capacity, mucosal erythema index and dental wear. STATISTICS: chi-square (Haberman post-hoc), ANOVA, and Mann-Whitney U; variables between visits were evaluated with McNemar's Student's t and Wilcoxon tests; p < 0.05. RESULTS: 100% of patients not taking xylitol-malic acid presented xerostomia, but only 14.3% of patients taking xylitol-malic acid (p < 0.01) did. The mean saliva-buffer capacity at the last visit for patients not taking xylitol-malic acid was 2.14 ± 0.38, versus 2.71 ± 0.49 for patients taking xylitol-malic acid (p < 0.05). Retro-sternal burning (p < 0.05), heartburn (p < 0.05) and regurgitation (p < 0.05) were also reduced. CONCLUSIONS: Xylitol-malic acid tablets improve quality of life among patients with GORD, by reducing dry mouth, increasing saliva buffering and reducing heartburn, retro-sternal burning and regurgitation.

Unusual Interface Dermatoses Distributed Along Blaschko's Lines in Adult Patients.

Linear dermatoses are unusual entities whose distribution reflects cutaneous mosaicism, even when they occur in adult life. Adult blaschkitis (AB) and lichen striatus (LS) always follow this peculiar distribution. Although usually referred to as distinct entities, the clinical and histopathological presentation of lichen striatus in adults may be similar to those of adult blaschkitis. Moreover, some cases with overlapping features between lichen striatus and linear lichen planus have been published, making precise diagnosis very difficult. Recently, the concept of a wide spectrum of blaschkolinear dermatoses with AB and LS located somewhere within it has been proposed but it has not gained general recognition. We report three cases of dermatoses following the lines of Blaschko in adults (two women and one male, ages 35, 50 and 56, respectively). They involved the upper extremity in two cases and the lower in the third. Clinically, they were interpreted as linear lichen planus or blaschkitis but, histopathologically, they showed features consistent with lichen striatus. Lesions subsided with topic steroids and/or tacrolimus ointment, they are an example of the significant overlapping between these three entities, demonstrating that they may exist on a spectrum both clinically and histopathologically and clinico-pathologic correlation is essential to achieve an accurate final diagnosis. A detailed review of previously published cases has also been made.

Neutrophilic panniculitis associated with alpha-1-antitrypsin deficiency: an update.

Neutrophilic panniculitis associated with alpha-1-antitrypsin deficiency (AATD) is a very rare disease. Its estimated prevalence is 1 in 1000 subjects with severe AATD (usually white individuals with a Pi*ZZ genotype). It is manifested clinically by painful recurrent ulcerating subcutaneous nodules, and characterized histologically by dense infiltrates of neutrophils in the deep dermis and connective-tissue septae, with secondary lobular panniculitis. It may be the only clinical manifestation of AATD, although it can also occur together with the classical pulmonary or hepatic manifestations of the disease. AATD-associated panniculitis is not only very rare but may also be significantly underdiagnosed. The physician managing a case of panniculitis with a clinical presentation suggestive of AATD and a compatible skin biopsy should measure serum AAT concentration and, if low, determine the AAT phenotype by isoelectric focusing. If uncertainty remains, the SERPINA1 gene should be sequenced to identify the genotype. If AATD is diagnosed, AATD testing of first-degree family members should be performed in order to take appropriate preventive and therapeutic measures, including genetic counselling, education on inheritance, risk arising from tobacco smoke, occupational exposure to pollutants and hepatotoxic substances, and the provision of information on clinical management. Cases of panniculitis in which conventional therapy with dapsone has failed may be managed with intravenous augmentative therapy using human AAT. The current manuscript addresses the fundamental concepts of the pathogenesis of AATD-associated panniculitis and describes the clinical presentation and management of cases in order to reduce underdiagnosis and improve outcomes.

Urinary high-mobility group box-1 associates specifically with lupus nephritis class V.

INTRODUCTION: High-mobility group box 1 protein (HMGB-1) has been implicated in the pathogenesis of lupus nephritis (LN). There is increased HMGB-1 expression in the kidneys and increased levels are observed in serum and urine of patients with LN. This study was performed to determine whether the increased urinary HMGB-1 was specific for active lupus or secondary to renal damage. METHODS: Urine from 61 lupus patients (32 had active LN and 29 had systemic lupus erythematosus (SLE) with no evidence of LN) and 14 control proteinuric patients (all with hypertension and eight also with diabetes) were included in this study. HMGB-1 was detected by Western blot. Urine protein was normalized to urine creatinine to account for volume of the specimen. RESULTS: Median normalized urine HMGB-1 levels were significantly elevated in LN patients compared to lupus patients without kidney disease (53.81 vs 9.46, p < 0.001). A difference in median levels was seen between LN classes, with a significant difference between proliferative and membranous disease (33.4 vs 138.8, p = 0.003). Urine protein to urine creatinine ratio (P/C) correlated with urinary HMGB-1 (r = 0.52, p < 0.001), but across the classes this was true only for membranous disease (r = 0.71, p = 0.022, proliferative, p = 0.63; mixed, p = 0.34). CONCLUSIONS: HMGB-1 is elevated in the urine of patients with active LN. Levels are associated with LN class, and higher levels of urinary HMGB-1 are seen in patients with class V when compared to both proliferative and mixed classes. Therefore, urinary HMGB-1 may be suggestive of membranous LN and warrants further evaluation in a large lupus cohort.

Barley Stripe Rust Resistance QTL: Development and Validation of SNP Markers for Resistance to Puccinia striiformis f. sp. hordei.

Quantitative trait loci (QTL) for barley stripe rust resistance were mapped in recombinant inbred lines (RIL) from a 'Lenetah' × 'Grannelose Zweizeilige' (GZ) cross. GZ is known for a major seedling resistance QTL on chromosome 4H but linked markers suitable for marker-assisted selection have not been developed. This study identified the 4H QTL (log of the likelihood [LOD] = 15.94 at 97.19 centimorgans [cM]), and additional QTL on chromosomes 4H and 6H (LOD = 5.39 at 72.7 cM and 4.24 at 34.46 cM, respectively). A QTL on chromosome 7H (LOD = 2.04 at 81.07 cM) was suggested. All resistance alleles were derived from GZ. Evaluations of adult plant response in Corvallis, OR in 2013 and 2015 provided evidence of QTL at the same positions. However, the minor QTL on 4H was not statistically significant in either location/year, while the 7H QTL was significant in both. The single-nucleotide polymorphism markers flanking the resistance QTL were validated in RIL from a '95SR316A' × GZ cross for their ability to predict seedling resistance. In 95SR316A × GZ, 91 to 92% of RIL with GZ alleles at the major 4H QTL and at least one other were resistant to moderate in reaction. In these populations, at least two QTL were required to transfer the barley stripe rust resistance from GZ.

Role of alpha-1 antitrypsin in human health and disease.

Alpha-1 antitrypsin (AAT) deficiency is an under-recognized hereditary disorder associated with the premature onset of chronic obstructive pulmonary disease, liver cirrhosis in children and adults, and less frequently, relapsing panniculitis, systemic vasculitis and other inflammatory, autoimmune and neoplastic diseases. Severe AAT deficiency mainly affects Caucasian individuals and has its highest prevalence (1 : 2000-1 : 5000 individuals) in Northern, Western and Central Europe. In the USA and Canada, the prevalence is 1: 5000-10 000. Prevalence is five times lower in Latin American countries and is rare or nonexistent in African and Asian individuals. The key to successful diagnosis is by measuring serum AAT, followed by the determination of the phenotype or genotype if low concentrations are found. Case detection allows implementation of genetic counselling and, in selected cases, the application of augmentation therapy. Over the past decade, it has been demonstrated that AAT is a broad-spectrum anti-inflammatory, immunomodulatory, anti-infective and tissue-repair molecule. These new capacities are promoting an increasing number of clinical studies, new pharmacological formulations, new patent applications and the search for alternative sources of AAT (including transgenic and recombinant AAT) to meet the expected demand for treating a large number of diseases, inside and outside the context of AAT deficiency.

Identification of a founder EPCAM deletion in Spanish Lynch syndrome families.

Germline deletions at the 3'-end of EPCAM have been involved in the etiology of Lynch syndrome (LS). The aim of this study was to characterize at the molecular level Spanish families harboring EPCAM deletions. Non-commercial multiplex ligation-dependent probe amplification (MLPA) probes and long-range polymerase chain reaction (PCR) amplification were used to characterize each deletion. Haplotyping was performed by analyzing eight microsatellite markers and five MSH2single nucleotide polymorphisms (SNPs). Methylation of MSH2 was analyzed by methylation specific-MLPA. Tumors diagnosed in seven Spanish families harboring EPCAM deletions were almost exclusively colorectal. Mosaicism in MSH2 methylation was observed in EPCAM deletion carrier samples, being average methylation levels higher in normal colon and colorectal tumors (27.6% and 31.1%), than in lymphocytes and oral mucosa (1.1% and 0.7%). Three families shared the deletion c.858 + 2568_*4596del, with a common haplotype comprising 9.9 Mb. In two families the novel EPCAM deletion c.858 + 2488_*7469del was identified. This study provides knowledge on the clinical and molecular characteristics of mosaic MSH2 epimutations. The identification of an EPCAM founder mutation has useful implications for the molecular diagnosis of LS in Spain.

Diagnostic accuracy of the faecal immunochemical test for colorectal cancer in symptomatic patients: comparison with NICE and SIGN referral criteria.

AIM: The diagnostic accuracy of the faecal immunochemical test (FIT) at a 100 ng/ml threshold for colorectal cancer (CRC) was compared with National Institute for Health and Care Excellence (NICE) and the Scottish Intercollegiate Guidelines Network (SIGN) referral criteria. METHOD: A multicentre, prospective, blind study of diagnostic tests was carried out in two Spanish health areas. In 787 symptomatic patients referred for a diagnostic colonoscopy, we determined whether patients met NICE and SIGN referral criteria. All patients performed one FIT determination (OCsensor(™) ). The sensitivity and specificity for CRC detection were determined with McNemar's test. The diagnostic odds ratio as well as the number needed to scope (NNS) to detect a CRC were calculated. RESULTS: We detected CRC in 97 (12.3%) patients; 241 (30.6%) had an FIT ≥ 100 ng/ml and 300 (38.1%) and 473 (60.1%) met NICE and SIGN referral criteria. The FIT had a higher sensitivity for CRC detection than NICE criteria (87.6%, 61.9%; P < 0.001) and SIGN criteria (82.5%; P = 0.4). The specificity of FIT was also higher than NICE and SIGN criteria (77.4%, 65.2%, 42.7%; P < 0.001). The odds ratios of FIT, NICE and SIGN criteria for the diagnosis of CRC were 24.24 (95% CI 12.91-45.53), 3.04 (95% CI 1.96-4.71) and 3.51 (95% CI 2.03-6.06). The NNS to detect a CRC in individuals with an FIT ≥ 100 ng/ml was 2.83 (95% CI 2.4-3.41) and in individuals who met NICE and SIGN criteria it was 5 (95% CI 3.98-6.37) and 5.95 (95% CI 4.85-7.35). CONCLUSION: Our study suggests that FIT is more accurate for the detection of CRC than the current NICE and SIGN referral criteria in symptomatic patients referred for colonoscopy.

Current status of prenatal diagnosis in Cuba: causes of low prevalence of Down syndrome.

OBJECTIVES: To analyze trends in cytogenetic prenatal diagnosis in Cuba and to analyze possible causes leading to a low Down syndrome prevalence in a country where the triple test is not available. METHODS: An analysis of the Cuban program in prenatal cytogenetic diagnosis from 1984 to 2012 was conducted. Results are described, with particular emphasis on indications, abnormal results, types of invasive procedures, and terminations of pregnancy. RESULTS: Cytogenetic prenatal diagnostic analyses (n = 75,095) were conducted; maternal age was the indication for 77.9% of the amniocenteses and chorionic villus samplings. The detection rate of chromosomally abnormal pregnancies was 2.3% for maternal age and increased to 8-9% for other indications. When a chromosomal abnormality was identified, 88.5% terminated the pregnancy. In 2002, the live birth prevalence of Down syndrome was 8.4 per 10,000 live births, and in 2012, 7 per 10,000. CONCLUSION: Prenatal diagnosis in Cuba has contributed to a significant reduction in chromosomal aberrations. The impact increased because of the demographic trends of the population, the high index of terminations of pregnancy, and the establishment of a network of cytogenetic laboratories throughout Cuba.

Multicenter longitudinal study of B-lymphocyte depletion in refractory systemic lupus erythematosus: the LESIMAB study.

OBJECTIVE: This study aimed to investigate the effectiveness and safety of single and repeated courses of rituximab in patients with refractory lupus. METHODS: LESIMAB is a multicenter, retrospective, longitudinal study of lupus patients who have not responded to standard therapy and have been treated with rituximab. Response rates at six months and at follow-up were defined as efficacy outcomes. Complete response was defined as a SELENA-SLEDAI score ≤ two and a SELENA-SLEDAI Flare Index of zero. Partial response was defined as a reduction in the SELENA-SLEDAI score of ≥four points with no new or worsening of symptoms. Adverse events were collected. RESULTS: Seventy-three (62.9%) of 116 patients achieved a response at six months (complete in 22 and partial in 51). Ninety-seven (77.6%) of 128 patients achieved a response after a mean follow-up of 20.0 ± 15.2 months (complete in 50 and partial in 47). High baseline SLEDAI score, previous treatment with ≥100 mg/day prednisone, and no history of severe hematologic flare were associated with response after the first treatment course. The median time to response was 6.5 months (95% CI, 5.0-8.0). Thirty-seven patients (38.1%) relapsed after the first infusion. The flare was severe in seven cases and mild to moderate in 29 cases. Serious infection rate was 12.6/100 patient-years. A schedule of four weekly doses was associated with more serious infections. Six patients died: two of infection and four of lupus complications. CONCLUSION: Rituximab can be an effective treatment option for patients who have refractory lupus with severe or life-threatening disease with an acceptable tolerance profile.

The role of temporal distance of the events on the spatiotemporal dynamics of mental time travel to one's personal past and future.

Mental time travel to personal past and future events shows remarkable cognitive and neural similarities. Both temporalities seem to rely on the same core network involving episodic binding and monitoring processes. However, it is still unclear in what way the temporal distance of the simulated events modulates the recruitment of this network when mental time-travelling to the past and the future. The present study explored the electrophysiological correlates of remembering and imagining personal events at two temporal distances from the present moment (near and far). Temporal distance modulated the late parietal component (LPC) and the late frontal effect (LFE), respectively involved in episodic and monitoring processes. Interestingly, temporal distance modulations differed in the past and future event simulation, suggesting greater episodic processing for near as opposed to far future situations (with no differences on near and far past), and the implementation of greater post-simulation monitoring processes for near past as compared to far past events (with high demands on both near and far future). These findings show that both past and future event simulations are affected by the temporal distance of the events, although not exactly in a mirrored way. They are discussed according to the increasing role of semantic memory in episodic mental time travel to farther temporal distances from the present.

Metabolic profile in endothelial cells of chronic thromboembolic pulmonary hypertension and pulmonary arterial hypertension.

Chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary arterial hypertension (PAH) are two forms of pulmonary hypertension (PH) characterized by obstructive vasculopathy. Endothelial dysfunction along with metabolic changes towards increased glycolysis are important in PAH pathophysiology. Less is known about such abnormalities in endothelial cells (ECs) from CTEPH patients. This study provides a systematic metabolic comparison of ECs derived from CTEPH and PAH patients. Metabolic gene expression was studied using qPCR in cultured CTEPH-EC and PAH-EC. Western blot analyses were done for HK2, LDHA, PDHA1, PDK and G6PD. Basal viability of CTEPH-EC and PAH-EC with the incubation with metabolic inhibitors was measured using colorimetric viability assays. Human pulmonary artery endothelial cells (HPAEC) were used as healthy controls. Whereas PAH-EC showed significant higher mRNA levels of GLUT1, HK2, LDHA, PDHA1 and GLUD1 metabolic enzymes compared to HPAEC, CTEPH-EC did not. Oxidative phosphorylation associated proteins had an increased expression in PAH-EC compared to CTEPH-EC and HPAEC. PAH-EC, CTEPH-EC and HPAEC presented similar HOXD macrovascular gene expression. Metabolic inhibitors showed a dose-dependent reduction in viability in all three groups, predominantly in PAH-EC. A different metabolic profile is present in CTEPH-EC compared to PAH-EC and suggests differences in molecular mechanisms important in the disease pathology and treatment.

Anal cytology screening in men who have sex with men with HIV at a university hospital in Bogotá, Colombia.

BACKGROUND: Risk of anal squamous cell carcinoma (anal cancer) is greater among men who have sex with men (MSM) living with human immunodeficiency virus (HIV). We describe the frequency of and factors associated with abnormal anal cytology results in Colombian MSM living with HIV. METHODS: This retrospective observational cohort study included MSM ≥18 years old living with HIV screened with anal cytology at Hospital Universitario San Ignacio in Bogotá, Colombia between January 2019 and February 2020. A multivariable log-binomial regression model estimated associations with abnormal anal cytology. RESULTS: A total of 211 patients were included. Mean age was 35.6 years. Sixty-eight (32.3%) had an abnormal anal cytology result: ASC-US 33.8% (n = 23); LSIL 60.3% (n = 41); and HSIL 5.9% (n = 4). MSM with an STI diagnosis in the previous 12 months (RR 1.48, [95% CI 1.03-2.12], p = 0.032) or with a CD4+ T cell count <200 (RR 2.08 [95% CI 1.16-3.73], p = 0.014) were significantly more likely to have abnormal anal cytology. CONCLUSIONS: These data provide crucial information to guide scale up of anal cancer screening at select centers in Colombia. Our results also suggest STI prevention efforts and improved virological control among MSM living with HIV may have the secondary benefit of reducing the risk of anal cancer.

Cetylpyridinium Chloride Mouthwash to Reduce Shedding of Infectious SARS-CoV-2: A Double-Blind Randomized Clinical Trial.

The airborne transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) via respiratory fluids and droplets suggests that mouthwashes containing substances with virucidal activity can help reduce viral spread. We conducted a multicenter, double-blind, placebo-controlled, randomized trial to assess the virucidal activity of cetylpyridinium chloride (CPC) mouthwashes. Outpatients who tested positive for SARS-CoV-2 infection with or without symptoms were randomized to perform washes and gargles for 1 min with 15 mL of either colored distilled water or 0.07% CPC (Vitis CPC Protect) mouthwash. The study outcomes were the SARS-CoV-2 log10 viral RNA load and the nucleocapsid protein levels, both in saliva at 1 and 3 h after the intervention. In total, 118 patients were enrolled and randomized (mean [SD], age 46 [14] y). Thirteen of 118 participants (11%) did not complete follow-up or had insufficient sample volume for testing and were excluded from the analysis. The assessment of the viral load showed no significant differences between groups at any of the investigated points. However, the levels of SARS-CoV-2 nucleocapsid protein of lysed viruses were significantly higher in the CPC group compared with the control group at 1 h (adjusted difference 269.3 pg/mL; 95% confidence interval [CI], 97.1-441.5) and at 3 h postintervention (561.1 pg/mL; 95% CI, 380.0-742.2). In nonhospitalized patients with asymptomatic or mild symptomatic SARS-CoV-2 infection, a 0.07% CPC mouthwash, compared to placebo, was associated with a significant increase of nucleocapsid protein levels in saliva, indicating enhanced disruption of viral particles.

Clinical and genetic characterization of classical forms of familial adenomatous polyposis: a Spanish population study.

BACKGROUND: Classical familial adenomatous polyposis (FAP) is characterized by the appearance of >100 colorectal adenomas. PATIENTS AND METHODS: We screened the APC and MUTYH genes for mutations and evaluated the genotype-phenotype correlation in 136 Spanish classical FAP families. RESULTS: APC/MUTYH mutations were detected in 107 families. Sixty-four distinct APC point mutations were detected in 95 families of which all were truncating mutations. A significant proportion (39.6%) had not been previously reported. Mutations were spread over the entire coding region and great rearrangements were identified in six families. Another six families exhibited biallelic MUTYH mutations. No APC or MUTYH mutations were detected in 29 families. These APC/MUTYH-negative families showed clinical differences with the APC-positive families. A poor correlation between phenotype and mutation site was observed. CONCLUSIONS: Our results highlight that a broad approach in the genetic study must be considered for classical FAP due to involvement of both APC and MUTYH and the heterogeneous spectrum of APC mutations observed in this Spanish population. The scarcely consistent genotype-phenotype correlation does not allow making specific recommendations regarding screening and management. Differences observed in APC/MUTYH-negative families may reflect a genetic basis other than mutations in APC and MUTYH genes for FAP predisposition.

Germline ATM mutational analysis in BRCA1/BRCA2 negative hereditary breast cancer families by MALDI-TOF mass spectrometry.

Biallelic inactivation of ATM gene causes the rare autosomal recessive disorder Ataxia-telangiectasia (A-T). Female relatives of A-T patients have a two-fold higher risk of developing breast cancer (BC) compared with the general population. ATM mutation carrier identification is laborious and expensive, therefore, a more rapid and directed strategy for ATM mutation profiling is needed. We designed a case-control study to determine the prevalence of 32 known ATM mutations causing A-T in Spanish population in 323 BRCA1/BRCA2 negative hereditary breast cancer (HBC) cases and 625 matched Spanish controls. For the detection of the 32 ATM mutations we used the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry technique. We identified one patient carrier of the c.8264_8268delATAAG ATM mutation. This mutation was not found in the 625 controls. These results suggest a low frequency of these 32 A-T causing mutations in the HBC cases in our population. Further case-control studies analyzing the entire coding and flanking sequences of the ATM gene are warranted in Spanish BC patients to know its implication in BC predisposition.