Managing IBD Patients with Concomitant HIV Infection - a Systematic Review.

PURPOSE OF REVIEW: Inflammatory Bowel Disease (IBD) is a chronic GI inflammatory condition induced by a dysregulated immune system activation, whereas HIV infection causes depletion of the immune system, inducing immunosuppression. Given the increasing incidence of IBD across the globe, including in developing countries, the co-prevalence of both conditions is expected to increase. Herein, we systematically review the data describing disease course when both pathologies co-exist. RECENT FINDINGS: Overall, the co-prevalence of IBD and HIV is around 0.1 to 2%. While IBD does not seem to affect HIV course, the opposite is controversial, as some studies report milder IBD phenotype, with fewer disease relapses especially when CD4 + counts are lower than 200 cells/µL. Despite growing evidence to support the safety of the use of immunosuppressants and biologics in IBD-HIV infected patients, these classes of drugs are used in less than 50% of patients, as compared to non-HIV infected IBD patients. There is a need for more studies on disease course and safety of IBD medications in the setting of IBD.

Comparison between the open and the laparoscopic approach in the primary ventral hernia repair: a systematic review and meta-analysis.

BACKGROUND: Ventral hernia repair underwent various developments in the previous decade. Laparoscopic primary ventral hernia repair may be an alternative to open repair since it prevents large abdominal incisions. However, whether laparoscopy improves clinical outcomes has not been systematically assessed. OBJECTIVES: The aim is to compare the clinical outcomes of the laparoscopic versus open approach of primary ventral hernias. METHODS: A systematic search of MEDLINE (PubMed), Scopus, Web of Science, and Cochrane Central Register of Controlled Trials was conducted in February 2023. All randomized controlled trials comparing laparoscopy with the open approach in patients with a primary ventral hernia were included. A fixed-effects meta-analysis of risk ratios was performed for hernia recurrence, local infection, wound dehiscence, and local seroma. Meta-analysis for weighted mean differences was performed for postoperative pain, duration of surgery, length of hospital stay, and time until return to work. RESULTS: Nine studies were included in the systematic review and meta-analysis. The overall hernia recurrence was twice less likely to occur in laparoscopy (RR = 0.49; 95%CI = 0.32-0.74; p < 0.001; I2 = 29%). Local infection (RR = 0.30; 95%CI = 0.19-0.49; p < 0.001; I2 = 0%), wound dehiscence (RR = 0.08; 95%CI = 0.02-0.32; p < 0.001; I2 = 0%), and local seroma (RR = 0.34; 95%CI = 0.19-0.59; p < 0.001; I2 = 14%) were also significantly less likely in patients undergoing laparoscopy. Severe heterogeneity was obtained when pooling data on postoperative pain, duration of surgery, length of hospital stay, and time until return to work. CONCLUSION: The results of available studies are controversial and have a high risk of bias, small sample sizes, and no well-defined protocols. However, the laparoscopic approach seems associated with a lower frequency of hernia recurrence, local infection, wound dehiscence, and local seroma.

Efficiency and safety of single anastomosis sleeve ileal (SASI) bypass in the treatment of obesity and associated comorbidities: a systematic review and meta-analysis.

INTRODUCTION: The Single Anastomosis Sleeve Ileal (SASI) bypass is a new bariatric surgery corresponding to an adaptation of the Santoro approach, consisting of a sleeve gastrectomy (SG) followed by loop gastroileostomy. Therefore, we aimed to systematically assess all the current literature on SASI bypass in terms of safety, weight loss, improvement in associated comorbidities, and complications. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta- Analyses (PRISMA) recommendations, we conducted a systematic review and meta-analysis by searching three databases (PubMed, Scopus, and Web of Science). We performed a meta-analysis of risk ratios and mean differences to compare surgical approaches for excessive weight loss, improvement/remission in type 2 diabetes mellitus (T2DM), hypertension (HT), dyslipidemia (DL), obstructive sleep apnea (OSA), and complications. Heterogeneity was assessed using the I2 statistic. RESULTS: Eighteen studies were included in the qualitative analysis and four in the quantitative analysis, comparing SASI bypass with SG and One-Anastomosis Gastric Bypass (OAGB). A comparison between Roux-en-Y Gastric Bypass (RYGB) and SASI bypass could not be performed. Compared to SG, the SASI bypass was associated with improved weight loss (MD = 11.32; 95% confidence interval (95%CI) [7.89;14.76]; p < 0.0001), and improvement or remission in T2DM (RR = 1.35; 95%CI [1.07;1.69]; p = 0.011), DL (RR = 1.41; 95%CI [1.00;1.99]; p = 0.048) and OSA (RR = 1.50; 95%CI [1.01;2.22]; p = 0.042). No statistically significant differences in any of the assessed outcomes were observed when compared with OAGB. When compared to both SG and OAGB, the complication rate of SASI was similar. CONCLUSION: Although studies with longer follow-up periods are needed, this systematic review and meta-analysis showed that SASI bypass has a significant effect on weight loss and metabolic variables. Variations in outcomes between studies reinforce the need for standardization.

Preoperative risk factors for early postoperative bleeding after Roux-en-Y gastric bypass surgery: a systematic review and meta-analysis.

PURPOSE: Although bariatric surgery is an effective intervention for obesity, it comes with risks such as early postoperative bleeding (EPB). Identifying preoperative risk factors for this complication can help patients' risk stratification and optimization. We performed a systematic review and meta-analysis to find predictors for early postoperative bleeding after Roux-en-Y gastric bypass (RYGB). METHODS: We conducted a systematic review, searching PubMed, Cochrane Library, and Web of Science until November 2023. We performed a random-effects meta-analysis to explore preoperative risk factors associated with early postoperative bleeding after RYGB. Sources of heterogeneity were explored by leave-one-out analyses. RESULTS: 23 studies were included, comprising 232,488 patients. Male gender (meta-analytical RR = 1.42, 95%CI = 1.21-1.66, I2 = 18%, Q Cochran test p-value = 0.29) and revisional surgery (meta-analytical RR = 1.35, 95%CI = 1.12-1.62, I2 = 22%, Q Cochran test p = 0.21) were associated with higher risk of EPB. On average, patients with EPB were older than the remainder (MD for the mean age = 2.82 years, 95%CI = 0.97-4.67, I2 = 0.00%, Q Cochran test p = 0.46). Except for hypertension (meta-analytical RR = 1.33, 95%CI = 1.02-1.73, I2 = 66%, Q Cochran test p < 0.0001), comorbidities were not associated with a higher risk of EPB. CONCLUSION: Preoperative risk factors, including age, gender, hypertension, and revisional bariatric surgery, are associated with early postoperative bleeding after RYGB. Further primary studies, with higher methodological quality, are required to detail more risk factors.

Impact of cervicovaginal microbiome on the risk of cervical abnormalities development.

The vaginal microbiome has emerged as potentially influencing the natural history of Human Papillomavirus (HPV) infections and their clinical impact. We aimed to characterize the vaginal microbiome in samples from 807 high-risk HPVs (Hr-HPV) positive women with a mean age of 41.45 ± 10.79 years who participated in the Regional Cervical Cancer Screening Program from the Northern Region of Portugal. Microbiome analysis was performed with commercial kits for the detection of 21 microorganisms. The most frequent microorganisms were Ureaplasma parvum (52.5%), Gardnerella vaginalis (GV) (34.5%), Atopobium vaginae (AV) (32.6%), Lacto (30.7%), and Mycoplasma hominis (MH) (23.5%). The distribution according to age reveals that MH, Mega1, GV, BVab2, AV, and Mob were more prevalent in women older than 41 years of age (p < 0.050), while Lacto is significantly decreased in this group (23.5% vs. 39.4%, p < 0.001; RR = 0.47). The risk analysis showed that Hr-HPV-16/-18 and Hr-HPV-9val genotypes are associated with an increased risk of developing cervical abnormalities, while Lacto (p < 0.001; odd ratio [OR] = 0.33), GV (p = 0.0111; OR = 0.41), AV (p = 0.033; OR = 0.53) and Mob (p = 0.022; OR = 0.29) are associated with protection. Similar results were found for the risk of development atypical squamous cells cannot exclude HSIL/high-grade squamous intraepithelial lesion. Overall, the multivariate analysis confirmed that lactobacillus and bacteria associated with bacterial vaginosis (GV, AV, and Mob) are associated with protection against the development of cervical abnormalities. This study provides important data to be included in the future management of risk stratification for Hr-HPV-positive women.

Impact of high-risk Human Papillomavirus genotyping in cervical disease in the Northern region of Portugal: Real-world data from regional cervical cancer screening program.

Cervical cancer prevention is based on primary prevention with vaccines against Human Papillomavirus (HPV) and secondary prevention by screening with High-Risk-HPV (Hr-HPV) detection. Since 2017, cervical cancer screening in women aged 25-60 years has been performed in Portugal using Hr-HPV detection, followed by cytology in Hr-HPV-positive cases. Herein we report the prevalence of Hr-HPV genotypes and cytological abnormalities among 462 401 women (mean age: 43.73 ± 10.79; median age: 45; range: 24-66 years) that participated in the Regional Cervical Cancer Screening Program of the Northern Region of Portugal, performed between August 2016 and December 2021. Overall, we describe a prevalence rate of 12.50% for Hr-HPV varying from 20.76% at age 25% to 8.32% at age 64. The five most common Hr-HPV genotypes identified were HPV-68 (16.09%), HPV-31 (15.30%), HPV-51 (12.96%), HPV-16 (11.06%), and HPV-39 (11.01%). The prevalence of Hr-HPV included in the nonavalent vaccine (HPV-9valent) was 55.00% ranging from 47.78% to 59.18% across different age groups. Considering positive Hr-HPV cases, 65.68% had a Negative for Intraepithelial Lesion or Malignancy (NILM) cytology, 20.83% atypical squamous cells of undetermined significance (ASC-US), 8.85% Low-Grade Squamous Intraepithelial Lesion (LSIL), 1.65% High-Grade Squamous Intraepithelial Lesion (HSIL), 2.85% ASC-H, 0.09% Atypical Glandular Cells, 0.02% Adenocarcinomas, and 0.02% Squamous Cell Carcinoma (SCC). Our analysis revealed that HPV-9val genotypes were responsible for 52.13% NILM, 59.21% ASC-US, 55.06% LSIL, 90.14% HSIL, 83.50% ASC-H, and 100.00% SCC. Furthermore, multiple Hr-HPV infections (risk ratio [RR] = 1.46; 95% confidence interval [CI] 1.34-1.58), HPV-16/18 (RR = 5.16; 95% CI 4.75-5.93), or HPV-9val genotypes (RR = 5.23; 95% CI 4.68-5.85) were associated with a significant risk of developing > HSIL (p < 0.001). To date, this is the largest study on Hr-HPV genotyping in cervical cancer screening that includes data from a complete cycle of the screening program. Our findings suggest a high prevalence of HPV-9valent genotypes and a significant association with an increased risk of developing > HSIL. This constitutes important data for health authorities, which may help define the future of vaccination and cervical cancer screening strategies.

Impact of serum albumin concentration and neutrophil-lymphocyte ratio score on gastric cancer prognosis.

INTRODUCTION/AIM: Serum albumin concentration (COA) and neutrophil-lymphocyte ratio (NLR) could reflect immunological and nutritional status. We aim to evaluate the impact of COA-NLR score on the prognosis of gastric cancer (GC). MATERIAL AND METHODS: We perform a retrospective analysis on a database of 637 GC cases, between January 2010 and December 2017. In 396 patients, the inclusion criteria for this study were met (non-resectional or palliative surgery were excluded). Analytic data was only available in 203 patients. COA-NLR score was defined as follows: COA under 35 g/L and NLR value of 2.585 or higher, score 2; one of these conditions, score 1; and neither, score 0. RESULTS: In our population (n = 203), 87 patients were classified as score 0, 82 as score 1 and 34 as score 2. COA-NLR score was significantly associated with DFS (HR 1.674; CI 95% 1.115-2.513; p = 0.013) and with OS (HR 2.072; CI 95% 1.531-2.805; p < 0.001). Kaplan-Meier curve analysis (log rank test) revealed that a higher score of COA-NLR predicted a worse OS (p < 0.001) and DFS (p = 0.03). COA-NLR was an independent prognostic factor for OS when adjusted to pStage and age (adjusted HR 1.566; CI 95% 1.145-2.143; p = 0.005). CONCLUSIONS: Preoperative COA-NLR score was significantly associated with worse OS and DFS and, in this way, with worse prognosis on GC patients submitted to curative-intent resectional surgery.

Roux-en-Y gastric bypass and sleeve gastrectomy as revisional bariatric procedures after adjustable gastric banding: a retrospective cohort study.

INTRODUCTION: The frequency of revisional bariatric surgery is increasing, but its effectiveness and safety are not yet fully established. The aim of our study was to compare short-term outcomes of primary (pRYGB and pSG) and revisional bariatric surgeries (rRYGB and rSG). METHODS: We performed a retrospective cohort study assessing all patients submitted to primary and revisional (after a failed AGB) RYGB and SG in 2019. Each patient was followed-up at 6 months and 12 months after surgery. We compared pRYGB vs. rRYGB, pSG vs. rSG and rRYGB vs. rSG on weight loss, surgical complications, and resolution of comorbidities. RESULTS: We assessed 494 patients, of which 18.8% had undergone a revisional procedure. Higher weight loss at 6 and 12 months was observed in patients undergoing primary vs. revisional procedures. Patients submitted to rRYGB lost more weight than those with rSG (%EWL 12 months = 82.6% vs. 69.0%, p < 0.001). Regarding the resolution of obesity-related comorbidities, diabetes resolution was more frequent in pRYGB than rRYGB (54.2% vs. 25.0%; p = 0.038). Also, 41.7% of the patients who underwent rRYGB had dyslipidemia resolution vs. 0% from the rSG group (p = 0.035). Dyslipidemia resolution was also more common in pSG vs. rSG (68.6% vs. 0.0%; p = 0.001). No significant differences in surgical complications were found. CONCLUSION: Revisional bariatric surgery is effective and safe treating obesity and related comorbidities after AGB. Primary procedures appear to be associated with better weight loss outcomes. Further prospective studies are needed to better understand the role of revisional bariatric surgery.

Incidence of symptomatic gallstones after bariatric surgery: the impact of expectant management.

BACKGROUND: Bariatric surgery is the most effective treatment for sustained weight reduction and obesity-related comorbidities. The development of gallstones as a result of rapid weight loss is a well-known consequence of bariatric procedures. It remains unclear, if there is an increased risk of these gallstones becoming symptomatic. METHODS: A retrospective analysis of 505 consecutive patients submitted to either Roux-en-Y Gastric Bypass or Sleeve Gastrectomy between January and December 2019 was performed. The aim of our study was to determine the incidence of symptomatic cholelithiasis in asymptomatic patients with their gallbladder in situ after bariatric surgery and to identify potential risk factors for its development. RESULTS: Of the 505 patients included, 79 (15.6%) underwent either previous cholecystectomy. (n = 67, 84.8%) or concomitant cholecystectomy during bariatric surgery (n = 12, 15.2%). Among the remaining 426 (84.4%) patients, only 8 (1.9%) became symptomatic during the 12-month follow-up period. When compared with patients who remained asymptomatic, they had a higher median preoperative BMI (47.0 vs. 42.8, p = 0.046) and prevalence of cholelithiasis on preoperative ultrasound (62.5% vs. 10.7%, p = 0.001). Multivariate analysis revealed preoperative BMI and cholelithiasis on preoperative ultrasound as independent risk factors for symptomatic biliary disease (OR 1.187, 95%CI 1.025-1.376, p = 0.022 and OR 10.720, 95%CI 1.613-71.246, p = 0.014, respectively). CONCLUSION: Considering a low incidence of symptomatic gallstones after bariatric surgery, concomitant cholecystectomy should only be performed in symptomatic patients undergoing bariatric surgery. Preoperative factors, such as a higher BMI and positive ultrasound for cholelithiasis, may be related to the development of symptomatic gallstones.

Using Raw Accelerometer Data to Predict High-Impact Mechanical Loading.

The purpose of this study was to develop peak ground reaction force (pGRF) and peak loading rate (pLR) prediction equations for high-impact activities in adult subjects with a broad range of body masses, from normal weight to severe obesity. A total of 78 participants (27 males; 82.4 ± 20.6 kg) completed a series of trials involving jumps of different types and heights on force plates while wearing accelerometers at the ankle, lower back, and hip. Regression equations were developed to predict pGRF and pLR from accelerometry data. Leave-one-out cross-validation was used to calculate prediction accuracy and Bland-Altman plots. Body mass was a predictor in all models, along with peak acceleration in the pGRF models and peak acceleration rate in the pLR models. The equations to predict pGRF had a coefficient of determination (R2) of at least 0.83, and a mean absolute percentage error (MAPE) below 14.5%, while the R2 for the pLR prediction equations was at least 0.87 and the highest MAPE was 24.7%. Jumping pGRF can be accurately predicted through accelerometry data, enabling the continuous assessment of mechanical loading in clinical settings. The pLR prediction equations yielded a lower accuracy when compared to the pGRF equations.

New Approaches in Early-Stage NSCL Management: Potential Use of PARP Inhibitors and Immunotherapy Combination.

Lung cancer is the second most common cancer in the world, being the first cause of cancer-related mortality. Surgery remains the only potentially curative treatment for Non-Small Cell Lung Cancer (NSCLC), but the recurrence risk remains high (30-55%) and Overall Survival (OS) is still lower than desirable (63% at 5 years), even with adjuvant treatment. Neoadjuvant treatment can be helpful and new therapies and pharmacologic associations are being studied. Immune Checkpoint Inhibitors (ICI) and PARP inhibitors (PARPi) are two pharmacological classes already in use to treat several cancers. Some pre-clinical studies have shown that its association can be synergic and this is being studied in different settings. Here, we review the PARPi and ICI strategies in cancer management and the information will be used to develop a clinical trial to evaluate the potential of PARPi association with ICI in early-stage neoadjuvant setting NSCLC.

Impact of Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy in the Treatment of Gastric Cancer with Peritoneal Carcinomatosis: A Systematic Review and Meta-analysis.

BACKGROUND: Despite promising results, the effectiveness of cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with gastric cancer with peritoneal carcinomatosis (GCPC) has not been systematically evaluated. The aim of this systematic review is to compare the survival, complications and risk of recurrence between CRS + HIPEC versus CRS alone in GCPC. PATIENTS AND METHODS: A systematic review was performed in MEDLINE and Web of Science according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Primary studies with patients with GCPC older than 18 years were included. Methodological Index for Non-randomized Studies (MINORS) criteria were used to assess the quality of the studies. We performed random-effects meta-analysis of risk ratios (RR). We assessed heterogeneity using the I2 statistic. RESULTS: Five studies were included in the qualitative and four in the quantitative analysis. The overall survival (OS) rate after 1 year was 3.65 times higher for CRS + HIPEC than CRS alone [RR = 3.65, 95% confidence interval (95% CI) = 1.01-13.26, I2 = 73%]. The OS rate after 5 years was more than three times higher for CRS + HIPEC than for CRS alone (RR = 3.25, 95% CI = 1.28-8.26, I2 = 8%). No significant differences between CRS + HIPEC and CRS alone related to complications were found (RR = 1.05, 95% CI = 0.83-1.33, I2 = 0%). The risk of peritoneal recurrence was significantly lower for CRS + HIPEC than for CRS alone (RR = 0.23, 95% CI = 0.11-0.48, I2 = 40%). The results may be associated with some information or indication bias. CONCLUSIONS: Results should be analysed cautiously given the detected heterogeneity and limitations of included studies. However, treatment with CRS + HIPEC seems to increase the survival of patients with GCPC, more than treatment with CRS alone, decrease the risk of peritoneal recurrence and not be associated with more complications.

Helicobacter species binding to the human gastric mucosa.

Helicobacter pylori infects half of the world population, being associated with several gastric disorders, such as chronic gastritis and gastric carcinoma. The Helicobacter genus also includes other gastric helicobacters, such as H. heilmannii¸ H. ailurogastricus, H. suis, H. felis, H. bizzozeronii, and H. salomonis. These gastric helicobacters colonize both the human and animal stomach. The prevalence of gastric non-Helicobacter pylori Helicobacter (NHPH) species in humans has been described as low, and the in vitro binding to the human gastric mucosa was never assessed. Herein, human gastric tissue sections were used for the evaluation of the tissue glycophenotype and for the binding of gastric NHPH strains belonging to different species. Histopathological evaluation showed that 37.5% of the patients enrolled in our cohort presented chronic gastritis, while the presence of neutrophil or eosinophilic activity (chronic active gastritis) was observed in 62.5% of the patients. The secretor phenotype was observed in 68.8% of the individuals, based on the expression of Lewis B antigen and binding of the UleX lectin. The in vitro binding assay showed that all the NHPH strains evaluated were able to bind, albeit in low frequency, to the human gastric mucosa. The H. heilmannii, H. bizzozeronii, and H. salomonis strains displayed the highest binding ability both to the gastric superficial epithelium and to the deep glands. Interestingly, we observed binding of NHPH to the gastric mucosa of individuals with severe chronic inflammation and intestinal metaplasia, suggesting that NHPH binding may not be restricted to the healthy gastric mucosa or slight chronic gastritis. Furthermore, the in vitro binding of NHPH strains was observed both in secretor and non-secretor individuals in a similar frequency. In conclusion, this study is the first report of the in vitro binding ability of gastric NHPH species to the human gastric mucosa. The results suggest that other glycans, besides the Lewis antigens, could be involved in the bacterial adhesion mechanism; however, the molecular intervenients remain unknown.

The impact of the prognostic nutritional index (PNI) in gastric cancer.

BACKGROUND: Regarding the assessment of patients' immune and nutritional status, prognostic nutritional index (PNI) has been reported as a predictive marker for surgical outcomes in various types of cancer. The aim of our study was to evaluate the effect of PNI in prognosis of gastric cancer patients submitted to curative-intent resectional surgery. MATERIAL AND METHODS: A retrospective analysis with 637 gastric cancer cases submitted to curative-intent surgery, between 2010 and 2017, in an upper GI surgery unit. We analyzed 396 patients that met the inclusion criteria for this study. The median follow-up was 37 (0-113) months. RESULTS: According to Youden's method, the optimal PNI cutoff for OS was 41.625 (sensitivity 89.3% and specificity 41.3%). OS was significantly shorter in the lower-PNI group of patients when compared to the higher-PNI group (40.26 vs 77.49 months; p < 0.001). Higher PNI had a positive impact on OS in univariable analysis. When adjusted to pStage, higher PNI was still significantly associated with better OS (HR 0.405; CI 95% 0.253-0.649; p < 0.001). Regarding DFS, higher PNI was associated with better DFS (HR 0.421; CI 95% 0.218-0.815; p = 0.010). Higher-PNI group had a protective effect regarding postoperative morbidity and mortality. CONCLUSIONS: In this cohort, PNI was disclosed to significantly impact GC patients' OS and DFS, including in multivariable analysis when adjusting for classical prognostic features. PNI can be used to predict patients at increased risk of postoperative morbidity and mortality. This index may be of use in identifying candidate patients who would benefit from perioperative nutritional support to improve surgical outcomes.

Effects of a Multicomponent Exercise Training Program on Balance Following Bariatric Surgery.

Patients who undergo bariatric surgery (BS) have an increased risk of falls. Our aim was to determine if a multicomponent exercise intervention after BS improves balance. Eighty-four patients with obesity enrolled for BS were recruited and 1 month after BS randomly allocated to a control (CG; standard medical care) or exercise group (EG; exercise plus standard medical care) consisting of a supervised multicomponent training program (3d/week; 75 min/session; 5 months). Anthropometry, lower limb muscle strength (isokinetic dynamometer), vitamin D (ELISA) and balance in bipedal stance (force platform) were assessed pre-BS, 1 month and 6 months post-BS. One month post-BS, significant balance improvements were observed, namely in antero-posterior center of gravity (CoG) displacement and velocity, and medio-lateral and total CoG velocity. Between 1- and 6-months post-BS, improvements in balance were observed only in the EG, with a significant treatment effect on CoG displacement area and antero-posterior CoG displacement. No significant differences were observed between EG and CG over time in any of the anthropometric, muscle strength, and vitamin D variables assayed. In conclusion, a multicomponent exercise intervention program improves some balance parameters in patients with severe obesity following BS and therefore should be part of post-BS follow-up care as a potential strategy to reduce falls and associated injuries.

Performance of DNA methylation-based biomarkers in the cervical cancer screening program of northern Portugal: A feasibility study.

Cervical cancer remains a health concern. Effective screening programs are critical to reduce the incidence and mortality. High-risk HPV (hr-HPV) testing as primary screening tool discloses high sensitivity but suboptimal specificity. Adequate triage tests to reduce unnecessary colposcopy referrals and overdiagnosis/overtreatment are crucial. Hence, we aimed to validate a panel of DNA methylation-based markers as triage test for women hr-HPV+ in the population-based Regional Cervical Cancer Screening Program of Northern Portugal. Firstly, CADM1, MAL, FAM19A4 and hsa-miR124-2 promoter methylation levels were assessed by multiplex QMSP in a testing set of 402 FFPE tissue samples (159 normal samples and 243 cervical lesions, including 39 low-grade intraepithelial squamous lesions [LSIL], 59 high-grade intraepithelial squamous lesions [HSIL] and 145 cancerous lesions). Then, preliminary validation was performed in 125 hr-HPV+ cervical scrapes (including 59 normal samples, 30 LSIL, 34 HSIL and 2 cancerous lesions). Higher MALme , FAM19A4me and hsa-miR124-2me methylation levels were disclosed in histological HSIL or worse (HSIL+) in testing set. Individually, markers depicted over 86% specificity for HSIL+ detection. In validation set, all these genes significantly differed between histological HSIL+ and low-grade squamous intraepithelial lesions or less. In combination, these markers reached 74% specificity and 61% sensitivity for identification of histological HSIL+. We concluded that host gene methylation might constitute a useful referral triage tool of hr-HPV+ women enrolled in the Cervical Cancer Screening Program of Northern Portugal.

Epstein-Barr virus strains and variations: Geographic or disease-specific variants?

The Epstein-Barr Virus (EBV) is associated with the development of several diseases, including infectious mononucleosis (IM), Burkitt's Lymphoma (BL), Nasopharyngeal Carcinoma, and other neoplasias. The publication of EBV genome 1984 led to several studies regarding the identification of different viral strains. Currently, EBV is divided into EBV type 1 (B95-8 strain) and EBV type 2 (AG876 strain), also known as type A and type B, which have been distinguished based upon genetic differences in the Epstein-Barr nuclear antigens (EBNAs) sequence. Several other EBV strains have been described in the past 10 years considering variations on EBV genome, and many have attempted to clarify if these variations are ethnic or geographically correlated, or if they are disease related. Indeed, there is an increasing interest to describe possible specific disease associations, with emphasis on different malignancies. These studies aim to clarify if these variations are ethnic or geographically correlated, or if they are disease related, thus being important to characterize the epidemiologic genetic distribution of EBV strains on our population. Here, we review the current knowledge on the different EBV strains and variants and its association with different diseases. J. Med. Virol. 89:373-387, 2017. © 2016 Wiley Periodicals, Inc.

Electrical stimulation structurally affects the tissues of the rectum and anus of nulliparous rats.

Considering that the muscles of the anus perform a critical role in maintaining continence, losses in their structure can negatively affect the physiological control of the intestinal contents. Anorectal electro-stimulation (ARES) has been reported to have a positive effect on the functionality of treated patients, but how ARES affects the structural tissues of the anorectal segment remains unknown. Because the study of how ARES structurally affects human tissues is not possible, this study aimed to clarify these effects in a murine model, which has a similar anorectal segment (structure and physiology) to humans. For the descriptive and comparative study, randomly selected nulliparous adult Wistar rats (n = 5) were submitted to 30 anorectal sessions of ARES with a biphasic current (700 µs, 50 Hz from 2 to 4 mA). After treatment, the animals were euthanized, and the anorectal segments were dissected and processed for histopathological analysis. Our results showed that ARES increased the widths of the mucosal, submucosal and muscle layers of the rectum, as well as the number of leukocytes in the mucosa. ARES also caused hyperplasia of the smooth muscle of the internal anal sphincter and hypertrophy of the external anal sphincter muscle. In conclusion, our results showed that ARES had not only a positive effect on the structure (morphology) of all tissues associated with the rectum and anus but, more importantly, on the structural gain of the muscles (hyperplasia and hypertrophy), which could point to a functional gain of the anal sphincter, reinforcing the applicability of ARES as a non-invasive treatment for anal incontinence.