Chronic NSAIDs Therapy and Upper Gastrointestinal Tract – Mechanism of Injury, Mucosal Defense, Risk Factors for Complication Development and Clinical Management

Non steroidal anti-inflammatory drugs (NSAIDs) are the most prescribed medications worldwide because of their analgesic and anti-inflammatory properties. In fact, NSAIDs are generally prescribed for pain management in musculoskeletal or osteoarticolar pathologies and for rheumatic diseases, very common diseases in the general population. About twenty million US patients were prescribed NSAIDs every year. Although NSAIDs are generally well tolerated, chronic therapy is responsible for a significant morbidity and mortality rate; in fact, the incidence of GI events is significantly higher (about four fold) in patients receiving NSAIDs chronic therapy. Adverse gastrointestinal events related to NSAIDs therapy occur in a little but significant amount of patients, resulting in an important morbidity and mortality. In the US more than 150 per 100.000 patients were admitted every year for NSAIDs related adverse events, resulting in about 15000 deaths. The chapter covers the mechanism of NSAIDs related injury, mucosal defense, risk factors for complication development and the clinical management

Lamivudine treatment for severe acute HBV hepatitis

Treatment for acute hepatitis B is recommended in order to reduce the risk of progression to fulminant hepatitis and the need of OLT. We report our experience on treatment with high dose lamivudine, in patients with severe acute HBV infection. The diagnosis was based on clinical and virological findings and exclusion of other known causes of liver damage. The decision to treat was based on the prolongation of INR together with increasing values of bilirubin and ALT. Four patients received Lamivudine 200 mg/daily until clearance of serum HBV-DNA and then 100 mg/daily until clearance of HBsAg and appearance of anti-HBs antibodies. One patient received 100 mg/daily because of chronic renal impairment. The median period of hospitalization was 13 days, and none of the patients had complications, related either to underlying disease or to therapy. The complete normalization of serum transaminases and bilirubin occurred on average after 5.5 weeks and 3 weeks respectively. All patients cleared serum HBV-DNA within three months, lost HBeAg and HBsAg and seroconverted to anti-HBe; four patients developed anti-HBs at a protective titre. Early antiviral treatment attenuates the clinical and biochemical impairment leading to fast healing and promoting complete recovery

Routine invasive mediastinal staging of lung cancer in elderly patients without lymph adenopathy on pet-ct scan: Is an appropriate choice?

We have reviewed the literature to clarify if routine invasive mediastinal staging is indicated also in Stage I elderly patients screened with PET/CT scan. Nineteen papers were chosen to answer the question. Occult pN2 disease was < 10% in five papers; between 10-16% in four papers; and > 16% in four papers.Significant risk factors for occult pN2 disease are the SUV value of primary tumor (seven papers), central tumor (four papers), tumor > 3 cm (five papers), adenocarcinoma histology (five papers) and cN1 disease(two papers). Two papers found that unexpected pN2 patients had a better survival than cN2 patients operated after induction therapy. Invasive mediastinal staging is recommended also in cN0 patients with central tumor or with peripheral tumor > 3 cm

Proposal of agreement upon cartographical parameters relevant to those Mediterranean areas characterised by coastal bentonic biocenosis

It has long been recognized within the field of science that a common methodology for mappingPosidonia oceanicameadows is required. This protocol aim at fixing cartographic parameter methods of investigation and precise navigation system that can be employed a references for the future activities along the coastal areas and the coastline

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Immune inflammation indicators and ALBI score to predict liver cancer in HCV-patients treated with direct-acting antivirals

Background: Unexpectedly high occurrence or recurrence rate of hepatocellular carcinoma (HCC) has been observed in patients with chronic hepatitis C receiving direct-acting antivirals (DAAs) therapy. Aims: We evaluated the predictive value of albumin-bilirubin (ALBI) score and immune-inflammation indicators to identify the risk of occurrence or recurrence of HCC in patients treated with DAAs in a real life setting. Methods: In this retrospective cohort study, we analysed data from 514 patients with cirrhosis who were prospectively enrolled for treatment with DAAs. We assessed baseline neutrophil to lymphocyte ratio (NLR), systemic immune-inflammation index (SII), platelet to lymphocyte ratio (PLR), aspartate aminotransferase-lymphocyte ratio (ALRI) index and ALBI score. Results: In patients with no history of HCC (N = 416), increased AST, bilirubin, ALRI, and ALBI score, and decreased albumin and platelets were significantly associated with an increased risk of HCC development, at univariate analysis. At multivariate analysis, increase in ALBI grade (p = 0.038, HR: 2.35, 95% CI: 1.05\u20135.25) and decrease in platelets (p = 0.048, HR: 0.92, 95% CI: 0.85\u20131.0) were independently associated with HCC development. In patients with previous HCC (N = 98), adjusting for the time from HCC treatment, increased ALRI (p = 0.008, HR: 1.05, 95% CI: 1.01\u20131.09) was significantly associated with a risk of recurrence. Conclusion: ALBI score, platelet count and ALRI are promising, easy to perform and inexpensive tools for identifying patients with higher risk of HCC after treatment with DAAs

Proposal of agreement upon cartographical parameters relevant to those Mediterranean areas characterised by coastal bentonic biocenosis

It has long been recognized within the field of science that a common methodology for mapping Posidonia oceanica meadows is required. This protocol aim at fixing cartographic parameter methods of investigation and precise navigation system that can be employed a references for the future activities along the coastal areas and the coastline

Imbalance of Neutrophils and Lymphocyte Counts Can Be Predictive of Hepatocellular Carcinoma Occurrence in Hepatitis C-related Cirrhosis Treated With Direct-acting Antivirals

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Hybrid immunity in older adults is associated with reduced SARS-CoV-2 infections following BNT162b2 COVID-19 immunisation

BACKGROUND: Older adults, particularly in long-term care facilities (LTCF), remain at considerable risk from SARS-CoV-2. Data on the protective effect and mechanisms of hybrid immunity are skewed towards young adults precluding targeted vaccination strategies.METHODS: A single-centre longitudinal seroprevalence vaccine response study was conducted with 280 LCTF participants (median 82 yrs, IQR 76-88 yrs; 95.4% male). Screening by SARS-CoV-2 polymerase chain reaction with weekly asymptomatic/symptomatic testing (March 2020-October 2021) and serology pre-/post-two-dose Pfizer-BioNTech BNT162b2 vaccination for (i) anti-nucleocapsid, (ii) quantified anti-receptor binding domain (RBD) antibodies at three time-intervals, (iii) pseudovirus neutralisation, and (iv) inhibition by anti-RBD competitive ELISA were conducted. Neutralisation activity: antibody titre relationship was assessed via beta linear-log regression and RBD antibody-binding inhibition: post-vaccine infection relationship by Wilcoxon rank sum test.RESULTS: Here we show neutralising antibody titres are 9.2-fold (95% CI 5.8-14.5) higher associated with hybrid immunity (p &lt; 0.00001); +7.5-fold (95% CI 4.6-12.1) with asymptomatic infection; +20.3-fold, 95% (CI 9.7-42.5) with symptomatic infection. A strong association is observed between antibody titre: neutralising activity (p &lt; 0.00001) and rising anti-RBD antibody titre: RBD antibody-binding inhibition (p &lt; 0.001), although 18/169 (10.7%) participants with high anti-RBD titre (&gt;100BAU/ml), show inhibition &lt;75%. Higher RBD antibody-binding inhibition values are associated with hybrid immunity and reduced likelihood of infection (p = 0.003).CONCLUSIONS: Hybrid immunity in older adults was associated with considerably higher antibody titres, neutralisation and inhibition capacity. Instances of high anti-RBD titre with lower inhibition suggests antibody quantity and quality as independent potential correlates of protection, highlighting added value of measuring inhibition over antibody titre alone to inform vaccine strategy.</p

Real-world survival outcomes of wedge resection versus lobectomy for cT1a/b cN0 cM0 non-small cell lung cancer: a single center retrospective analysis

BackgroundJCOG0802/WJOG4607L showed benefits in overall survival (OS) of segmentectomy. CALGB 140503 confirmed that sublobar resection was not inferior to lobectomy concerning recurrence-free survival (RFS) but did not provide specific OS and RFS according to the techniques of sublobar resections. Hence, we retrospectively analyze the survival differences between wedge resection and lobectomies for stage IA lung cancer.MethodsWe reviewed the clinical records of patients with clinical stage IA NSCLC over 20 years. The inclusion criteria were: preoperative staging with CT scan and whole body CT/PET; tumor size &lt;20 mm; wedge resections or lobectomies with or without lymph node dissection; NSCLC as the only primary tumor during the follow-up period. We excluded: multiple invasive lung cancer; positive resection margin; preoperative evidence of nodal disease; distant metastasis at presentation; follow-up time &lt;5 years. The reverse Kaplan – Meier method estimated the median OS and PFS and compared them by the log-rank test. The stratified backward stepwise Cox regression model was employed for multivariable survival analyses.Results539 patients were identified: 476 (88.3%) lobectomies and 63 (11.7%) wedge resections. The median OS time for the whole cohort was 189.7 months (range: 173.7 – 213.9 months). The 5-year wedge resection and lobectomy OS were 82.2% and 87.0%. The 5-year RFS of wedge resection and lobectomy were 17.8% and 28.9%. The log-rank test showed no significant differences (p = 0.39) between wedge resections and lobectomies regarding OS and RFS (p = 0.23).ConclusionsLobectomy and wedge resection are equivalent oncologic treatments for individuals with cN0/cM0 stage IA NSCLC &lt;20 mm. Validating the current findings requires a prospective, randomized comparison between wedge resection and standard lobectomy to establish the prognostic significance of wedge resection