Percentage of intrathoracic stomach predicts operative and post-operative morbidity, persistent reflux and PPI requirement following laparoscopic hiatus hernia repair and fundoplication.

PURPOSE: Large hiatus hernias are relatively common and can be associated with adverse symptoms and serious complications. Operative repair is indicated in this patient group for symptom management and the prevention of morbidity. This study aimed to identify predictors of poor outcomes following laparoscopic hiatus hernia repair and fundoplication (LHHRaF) to aid in counselling potential surgical candidates. METHODOLOGY: A retrospective analysis was performed from a prospectively maintained, multicentre database of patients who underwent LHHRaF between 2014 and 2020. Revision procedures were excluded. Hernia size was defined as the intraoperative percentage of intrathoracic stomach, estimated by the surgeon to the nearest 10%. Predictors of outcomes were determined using a prespecified multivariate logistic regression model. RESULTS: 625 patients underwent LHHRaF between 2014 and 2020 with 443 patients included. Median age was 65 years, 62.9% were female and 42.7% of patients had ≥ 50% intrathoracic stomach. In a multivariate regression model, intrathoracic stomach percentage was predictive of operative complications (P = 0.014, OR 1.05), post-operative complications (P = 0.026, OR 1.01) and higher comprehensive complication index score (P = 0.023, OR 1.04). At 12 months it was predictive of failure to improve symptomatic reflux (P = 0.008, OR 1.02) and persistent PPI requirement (P = 0.047, OR 1.02). Operative duration and blood loss were predicted by BMI (P = 0.004 and < 0.001), Type III/IV hernias (P = 0.045 and P = 0.005) and intrathoracic stomach percentage (P = 0.009 and P < 0.001). Post-operative length of stay was predicted by age (P < 0.001) and emergency presentation (P = 0.003). CONCLUSION: In a multivariate regression model, intrathoracic stomach percentage was predictive of operative and post-operative morbidity, PPI use, and failure to improve reflux symptoms at 12 months.

Palm cooling temperatures on thermal, physiological, perceptual, and ergogenic indices from rowing workouts in a thermoneutral environment.

Gel pack temperatures were compared for responses to thermal, physiological, perceptual, and ergogenic indices from healthy women (n = 12) and men (n = 8). They did three rowing workouts to identify an ideal temperature. In a randomised sequence, and as subjects wore gloves equipped with mesh pouches during workouts, gel packs at one of the three average temperatures (10.6, 12.6, or 14.9°C) were inserted into the pouches. Data were collected before, during and after multi-stage workouts. Thermal, physiological, and perceptual data were each compared with three-factor (condition, gender, time) mixed effect model ANCOVAs, with repeated measures for condition and time, and gender as a between subjects' factor. Distance rowed was assessed with two-factor (condition, gender) mixed effect model ANCOVAs, with repeated measures for condition, and gender as a between subjects' factor. Within-subject contrasts was the post-hoc, and α = 0.05 denoted significance. Despite small differences for distance rowed, many dependent variables had significant inter-condition effects, whereby 10.6°C gel packs had the best thermal and physiological responses. The 10.6°C temperature 1): likely removed the most body heat, perhaps through cold-induced vasodilation and, 2): may be optimal, as it evoked the best thermal and physiological responses.

Whole-Genome Sequences of Two Klebsiella pneumoniae Strains (Sequence Types 23 and 35) from Wildlife.

This report describes the draft genomes of two Klebsiella pneumoniae strains that were isolated from two wild boars collected during epidemiological surveillance and monitoring of wild fauna in the Abruzzo and Molise regions. The strains belonged to sequence type 23 (ST23) and ST35, which are frequently reported in clinical cases.

Real-life efficacy and safety of Ustekinumab as second- or third-line therapy in Crohn's disease: results from a large Italian cohort study.

OBJECTIVE: Ustekinumab (UST) is an anti-IL12/23 antibody for the treatment of Crohn's Disease (CD). The aim of this study was to compare the efficacy and safety of UST in a large population-based cohort of CD patients who failed previous treatment with other biologics. PATIENTS AND METHODS: 194 CD patients (108 males and 86 females, mean age 48 years (range 38-58 years) were retrospectively reviewed. 147 patients were already treated with anti-TNFα (75.8%), and 47 (24.2%) patients were already treated with anti-TNFα and vedolizumab. Concomitant treatment with steroids was present in 177 (91.2%) patients. RESULTS: At week 12, clinical remission was achieved in 146 (75.2%) patients. After a mean follow-up of 6 months, clinical remission was maintained in 135 (69.6%) patients; at that time, mucosal healing was assessed in 62 (31.9%) patients, and it was achieved in 33 (53.2) patients. Three (1.5%) patients were submitted to surgery. Steroid-free remission was achieved in 115 (59.3%) patients. Both serum C-Reactive Protein and Fecal Calprotectin (FC) levels were significantly reduced with respect to baseline levels during follow-up. A logistic regression, UST therapy as third-line therapy (after both anti-TNFα and vedolizumab), FC >200 µg/g, and HBI ≥8 were significantly associated with lack of remission. Adverse events occurred in 5 (2.6%) patients, and four of them required suspension of treatment. CONCLUSIONS: UST seemed to be really effective and safe in CD patients unresponsive to other biologic treatments, especially when used as second-line treatment.

Cucullanus carettae Baylis, 1923, in a loggerhead sea turtle (Caretta caretta) from the Adriatic sea: first detection and molecular characterization.

Cucullanus carettae Baylis, 1923 (Nematoda: Cucullanidae) is found worldwide in loggerhead turtles (Caretta caretta). Regarding the Mediterranean, C. carettae has been identified in the Tyrrhenian and the Ionian Sea and a unique description of a Cucullanus sp. specimen in loggerheads from the Adriatic Sea has been reported in the literature so far. In the framework of a bio-monitoring project of the Abruzzo and Molise coasts, a parasitological survey was performed on stranded and by-caught sea turtles, at the Istituto Zooprofilattico of Abruzzo and Molise "G. Caporale." During necropsy, the gastrointestinal system of 72 stranded loggerhead turtles was analyzed for the presence of endoparasites and fecal samples were collected for coprological examination. Adult C. carettae (n = 123) was found in the upper intestine of one loggerhead turtle, associated with chronic lymphoplasmocytic enteritis. Additionally, five stool samples (6.9%) were positive for Cucullanus sp. eggs. Molecular characterization of adult nematodes was carried out to study phylogenetic relationships among the Cucullanus species. To our knowledge, this is the first morphological and molecular identification of C. carettae in loggerhead turtles from the Adriatic Sea. Additional studies on the distribution of this parasite in the Mediterranean are encouraged.

Point-of-care Hepatitis C virus testing and linkage to treatment in an Australian inner-city emergency department.

BACKGROUND: In Australia, Hepatitis C Virus (HCV) treatment is declining, despite broad access to direct-acting antiviral medication. People who inject drugs are proportionally over-represented in emergency department presentations. Emergency department assessment of people who have injected drugs for HCV presents an opportunity to engage this marginalised population with treatment. We describe the outcomes of risk-based screening and point-of-care anti-HCV testing for emergency department patients, and linkage to outpatient antiviral treatment. METHODS: During the three-month study period, consecutive adult patients who presented to the emergency department during the study times were screened for risk factors and offered the OraQuick oral HCV antibody test. Those with reactive results were offered venepuncture in the emergency department for confirmatory testing and direct-acting antiviral treatment in clinic. The main outcome measures were the number and proportion of viremic participants that were linked to the hepatitis clinic, commenced treatment and achieved a sustained viral response. Secondary outcome measures were the proportion (%) of presentations screened that were oral antibody reactive, and the prevalence and type of HCV risk factors. RESULTS: During the study period, 2408 of the 3931 (61%) presentations to the emergency department were eligible for screening. Of these 2408 patients, 1122 (47%) participated, 307 (13%) declined participation and 977 (41%) could not be approached during their time in the emergency department. Among the 1122 participants, 378 (34%) reported at least one risk factor. Subsequently, 368 (97%) of the 378 participants underwent OraQuick anti-HCV test, and 50 (14%) had a reactive result. A risk factor of ever having injected drugs was present in 44 (88%) of participants who were sero-positive. Of the 45 that had blood tested, 30 (67%) were HCV ribonucleic acid (RNA) positive. Three participants died. Of the 27 remaining participants, 10 (37%) commenced treatment and 7 of these 10 (70%) obtained a cure. There was a high rate of homelessness (24%) among anti-HCV positive participants. CONCLUSION: Among emergency department participants with a risk factor for HCV, positive serology was common using a rapid point-of-care test. A history of injecting drug use was identified as the risk factor with highest yield for positive HCV serology, and is suitable as a single screening question. However, linkage to care post ED presentation was low in this marginalised population. There is a need for new pathways to improve the care cascade for marginalised individuals living with HCV infection.

Constraints on Sub-GeV Dark-Matter-Electron Scattering from the DarkSide-50 Experiment.

We present new constraints on sub-GeV dark-matter particles scattering off electrons based on 6780.0 kg d of data collected with the DarkSide-50 dual-phase argon time projection chamber. This analysis uses electroluminescence signals due to ionized electrons extracted from the liquid argon target. The detector has a very high trigger probability for these signals, allowing for an analysis threshold of three extracted electrons, or approximately 0.05 keVee. We calculate the expected recoil spectra for dark matter-electron scattering in argon and, under the assumption of momentum-independent scattering, improve upon existing limits from XENON10 for dark-matter particles with masses between 30 and 100 MeV/c^{2}.

Low-Mass Dark Matter Search with the DarkSide-50 Experiment.

We present the results of a search for dark matter weakly interacting massive particles (WIMPs) in the mass range below 20 GeV/c^{2} using a target of low-radioactivity argon with a 6786.0 kg d exposure. The data were obtained using the DarkSide-50 apparatus at Laboratori Nazionali del Gran Sasso. The analysis is based on the ionization signal, for which the DarkSide-50 time projection chamber is fully efficient at 0.1 keVee. The observed rate in the detector at 0.5 keVee is about 1.5 event/keVee/kg/d and is almost entirely accounted for by known background sources. We obtain a 90% C.L. exclusion limit above 1.8 GeV/c^{2} for the spin-independent cross section of dark matter WIMPs on nucleons, extending the exclusion region for dark matter below previous limits in the range 1.8-6 GeV/c^{2}.

Influence of Surface Treatment on Composite Adhesion in Noncarious Cervical Lesions: Systematic Review and Meta-analysis.

The purpose of this study was to analyze the influence of dentin surface treatments on the retention rate of resin composite restorations in non-carious cervical lesions (NCCLs). Seven randomized clinical trials were included in this review. Data regarding retention rate, type of surface treatment, and the main characteristics of studies were analyzed. Two reviewers performed a literature search up to December 2016 in eight databases: PubMed (Medline), Lilacs, Ibecs, Web of Science, BBO, Scopus, Scielo and The Cochrane Library. Only clinical trials evaluating dentin surface treatments in resin composite restoration in NCCLs were included. Noncontrolled clinical trials, reviews, editorial letters, case reports, case series and studies published in a language other than English, Portuguese, or Spanish were not included. The included studies evaluated different surface treatments, such as using an adhesive system with a frictional technique, drying the dentin, and removing sclerotic dentin by using a bur and applying EDTA before primer use. The analysis considering the mechanical removal of dentin surface with a bur and the application of an adhesive system in a frictional mode showed these treatments improved retention rates of the resin composite restorations in NCCLs ( p<0.05). There is evidence in the literature suggesting that the mechanical removal of dentin surface with a bur and the application of an adhesive system in a frictional mode could improve the retention rates of resin composite restorations in NCCLs. However, the studies showed high heterogeneity, and additional clinical trials are needed to determine the best dentin treatment option in NCCLs.

Effects of delayed mating on the reproductive biology of the vine mealybug, Planococcus ficus (Hemiptera: Pseudococcidae).

The effect of increasing mating delay on the reproductive performance and population growth rates of the vine mealybug, Planococcus ficus (Signoret) (Hemiptera: Pseudococcidae), was investigated under laboratory conditions. Virgin females were mated at 1, 3, 5, 7, 14, 21 and 28 days after emergence and reproductive and life table parameters were estimated. The pre-oviposition period (number of days between mating and the onset of oviposition) significantly decreased in females mated within 7 days, whereas females mated at older ages showed equivalent pre-oviposition periods (7 days, as shorter delays in mating did not reduce the population growth rates.

Treatment of Fluorosis Spots Using a Resin Infiltration Technique: 14-month Follow-up.

The aim of this study was to report a clinical case of moderate fluorosis spots treated with infiltration of low-viscosity resin. A commercial resin was applied to the facial surfaces on the anterior teeth in both the maxillary and mandibular arches. The white spots of fluorosis lost their whitish appearance and appeared similar to sound enamel. This technique, which might constitute an alternative to white-masking of fluorosis spots, showed optimal esthetic results.

Detection of Anaplasma phagocytophilum genotypes that are potentially virulent for human in wild ruminants and Ixodes ricinus in Central Italy.

Human granulocytic anaplasmosis (HGA) is an emerging tick-borne zoonosis worldwide. As is the case for many tick-borne diseases, the epidemiological cycle is associated to the environmental conditions, including the presence of wild vertebrate reservoir hosts, vectors, climate and vegetation. In this study a total number of 87 spleen samples of wild ruminants carcasses from Central Italy, and 77 Ixodes ricinus collected from the same dead animals were screened for Anaplasma phagocytophilum by using Real Time PCR. A. phagocytophilum DNA was detected in 75%, 66.7% and 54.2% of the spleen samples from red deer (Cervus elaphus), Apennine chamois (Rupicapra pyrenaica ornata) and roe deer (Capreolus capreolus) respectively, whereas it was detected in the 31.2% of I. ricinus. A total of 27 positive samples were characterized by sequencing a portion of the groEL gene. Two A. phagocytophilum lineages could clearly be delineated from the phylogenetic tree. Four sequences from red deer, 2 from I. ricinus and 1 from Apennine chamois clustered into lineage I together with those previously described as virulent genotypes related to HGA. The presence of A. phagocytophilum DNA in the Apennine chamois represents the first report for this Italian endemic subspecies.

[Use of argon plasma coagulation in digestive endoscopy: a concise review]. / Utilizzo della coagulazione con argon plasma in endoscopia digestiva: revisione della letteratura.

Argon plasma coagulation (APC) is a non-contact thermal method of hemostasis that has generated much attention in recent years. This endoscopic procedure is used primarily to control bleeding from lesions in the gastrointestinal tract, and also sometimes to debulk tumours in the case of patients for whom surgery is not recommended. APC involves the use of a jet of ionized argon gas (plasma) that is directed through a probe passed through the endoscope. The probe is placed at some distance from the lesion, and tissue damage is limited to superficial layers. The depth of coagulation is usually only a few millimetres. Theoretical advantages of APC include facility application, speedy treatment of multiple lesions in the case of angiodysplasias or wide areas (the base of resected polyps or tumor bleeding), safety due to reduced depth of penetration, and lower cost compared to laser.

Clinical course of Crohn's disease first diagnosed at surgery for acute abdomen.

BACKGROUND: The severity of clinical activity of Crohn's disease is high during the first year after diagnosis and decreases thereafter. Approximately 50% of patients require steroids and immunosuppressants and 75% need surgery during their lifetime. The clinical course of patients with Crohn's disease first diagnosed at surgery has never been investigated. AIM: To assess the clinical course of Crohn's disease first diagnosed at surgery for acute abdomen and to evaluate the need for medical and surgical treatment in this subset of patients. PATIENTS AND METHODS: Hospital clinical records of 490 consecutive Crohn's disease patients were reviewed. Patients were classified according to the Vienna criteria. Sex, extraintestinal manifestations, family history of inflammatory bowel diseases, appendectomy, smoking habit and medical/surgical treatments performed during the follow-up period were assessed. STATISTICAL ANALYSIS: Kaplan-Meier survival method and Cox proportional hazards regression model. RESULTS: Of the 490 Crohn's disease patients, 115 had diagnosis of Crohn's disease at surgery for acute abdomen (Group A) and 375 by conventional clinical, radiological, endoscopic and histologic criteria (Group B). Patients in Group A showed a low risk of further surgery (Log Rank test p<0.001) and a longer time interval between diagnosis and first operation compared to Group B (10.8 years vs. 5.8 years, p<0.01, respectively). Furthermore, patients in Group A used less steroids and immunosuppressants (OR 0.3, p<0.0001; OR 0.6, p<0.004, respectively). CONCLUSIONS: Crohn's disease patients first diagnosed at surgery for acute abdomen showed a low risk for reintervention and less use of steroids and immunosuppressants during follow-up than those not operated upon at diagnosis. Early surgery may represent a valid approach in the initial management of patients with Crohn's disease, at least in the subset of patients with ileal and complicated disease.

European evidence based consensus on the diagnosis and management of Crohn's disease: special situations.

This third section of the European Crohn's and Colitis Organisation (ECCO) Consensus on the management of Crohn's disease concerns postoperative recurrence, fistulating disease, paediatrics, pregnancy, psychosomatics, extraintestinal manifestations, and alternative therapy. The first section on definitions and diagnosis reports on the aims and methods of the consensus, as well as sections on diagnosis, pathology, and classification of Crohn's disease. The second section on current management addresses treatment of active disease, maintenance of medically induced remission, and surgery of Crohn's disease.

Early or late guided missile in the treatment of Crohn's disease?

Over the last few years, much light has been shed on the pathogenesis of Crohn's disease. Further knowledge in this field has provided a firm basis not only in the understanding of current treatment but also for the development of new therapeutic strategies. Aim of these new agents is primarily to selectively interact with the key processes of intestinal inflammation. At present, only anti-tumour necrosis factor-alpha antibodies namely infliximab, is licensed for clinical practice but it is feasible to foresee that, in the near future, a larger range of these agents will become available. Herein, the most promising biological agents in the treatment of Crohn's disease are outlined, which patients would benefit from these agents and when they should be administered. Attention is focused on the early (top-down) or late (step-up) use of biological agents, which for their very targeted mechanism of action may be compared to guided missiles. As yet, early use of biological agents remains to be supported by convincing evidence, nevertheless it may be advocated as first-line therapy for newly diagnosed severe Crohn's disease patients, both adults and children.

Potent isozyme-selective inhibition of human glutathione S-transferase A1-1 by a novel glutathione S-conjugate.

Elevated levels of glutathione S-transferases (GSTs) are among the factors associated with an increased resistance of tumors to a variety of antineoplastic drugs. Hence a major advancement to overcome GST-mediated detoxification of antineoplastic drugs is the development of GST inhibitors. Two such agents have been synthesized and tested on the human Alpha, Mu and Pi GST classes, which are the most representative targets for inhibitor design. The novel fluorescent glutathione S-conjugate L-gamma-glutamyl-(S-9-fluorenylmethyl)-L-cysteinyl-glycine (4) has been found to be a highly potent inhibitor of human GSTA1-1 in vitro (IC50=0.11+/-0.01 microM). The peptide is also able to inhibit GSTP1-1 and GSTM2-2 isoenzymes efficiently. The backbone-modified analog L-gamma-(gamma-oxa)glutamyl-(S-9-fluorenylmethyl)-L-cysteinyl-glycine (6), containing an urethanic junction as isosteric replacement of the gamma-glutamyl-cysteine peptide bond, has been developed as gamma-glutamyl transpeptidase-resistant mimic of 4 and evaluated in the same inhibition tests. The pseudopeptide 6 was shown to inhibit the GSTA1-1 protein, albeit to a lesser extent than the lead compound, with no effect on the activity of the isoenzymes belonging to the Mu and Pi classes. The comparative loss in biological activity consequent to the isosteric change confirms that the gamma-glutamyl moiety plays an important role in modulating the affinity of the ligands addressed to interact with GSH-dependent proteins. The new specific inhibitors may have a potential in counteracting tumor-protective effects depending upon GSTA1-1 activity.

Appropriateness of immunosuppressive drugs in inflammatory bowel diseases assessed by RAND method: Italian Group for IBD (IG-IBD) position statement.

INTRODUCTION: Despite the explosion of biological therapies, the old immunosuppressants continue to play a pivotal role in the management of inflammatory bowel diseases. AIM: To assess the appropriateness of immunosuppressants-azathioprine, 6-mercaptopurine, methotrexate, cyclosporine A, tacrolimus (FK506), mycophenolate mofetil and thalidomide-in the treatment of inflammatory bowel disease by using RAND/University of California Appropriateness Method. METHODS: The RAND method consists of a combination of evidence from the literature and experts' opinions. Appropriateness has been defined to mean that the expected health benefit exceeds the expected negative consequences by a sufficiently wide margin. A panel of 10 experts from the Italian Group for Inflammatory Bowel Disease has rated, in two rounds, on a scale from 1 to 9, the appropriateness of each indication selected by the Promoter Centre, on the basis of their own clinical experience. An indication was considered appropriate if the median of the panelists' ratings fell within the area 7-9, inappropriate in the area 1-3 and uncertain in the area 4-6. A total of 2781 indications were grouped into 13 categories (mild to moderate Crohn's disease; severe Crohn's disease; fistulizing Crohn's disease; steroid-dependant and -resistant Crohn's disease; maintenance of remission induced by medical treatment in Crohn's disease; maintenance of remission induced by surgery in Crohn's disease; mild to moderate ulcerative colitis; severe ulcerative colitis; steroid-dependant and -resistant ulcerative colitis; maintenance of remission induced by medical treatment in ulcerative colitis; extra-intestinal manifestations in inflammatory bowel disease; pregnancy and inflammatory bowel disease; azathioprine-resistant or -intolerant inflammatory bowel disease patients). RESULTS: Of the 2781 scenarios, 212 (7.6%) were rated appropriate, 645 (23.2%) uncertain and 1924 (69.2%) inappropriate. The most relevant results were: in steroid-dependant or -resistant Crohn's disease, azathioprine, 6-mercaptopurine and methotrexate were defined as appropriate in 25 (86.2%) and 14 (48.3%) of the 29 scenarios respectively; in Crohn's disease, azathioprine and 6-mercaptopurine were defined as appropriate combined with Infliximab (bridge therapy); in steroid-dependant or -resistant ulcerative colitis, azathioprine and 6-mercaptopurine were defined as appropriate in 45 (77.6%) out of 58 scenarios, while methotrexate was defined appropriate only after previous azathioprine failure; in severe ulcerative colitis, cyclosporine A was defined as appropriate only after previous failure with steroids; in azathioprine-intolerant or -resistant inflammatory bowel disease patients, methotrexate was appropriate in 20 (66.7%) out of 30 scenarios; it is inappropriate to stop azathioprine treatment before conception in the presence of active disease. The use of FK506, mycophenolate mofetil and Thalidomide resulted as inappropriate or uncertain. CONCLUSIONS: Results of this study show that only azathioprine, 6-mercaptopurine and methotrexate are appropriate in the treatment of inflammatory bowel diseases. Cyclosporine A was found to be appropriate only in severe ulcerative colitis after the failure of steroids. FK506, mycophenolate mofetil and Thalidomide resulted as inappropriate but experience with these agents is somewhat limited.