Effectiveness of preoperative micronized purified flavonoid fraction treatment and sucralfate-based rectal ointment on hemorrhoidal disease: A case-matched analysis.

BACKGROUND: Hemorrhoidal disease (HD) significantly impacts patients' quality of life. This study aimed to evaluate the effectiveness of preoperative treatment with the micronized purified flavonoid fraction (MPFF) and a sucralfate-based rectal ointment in managing HD symptoms and reducing interventions. METHODS: A prospective quasi-experimental study including consecutive cases and controls matched on the basis of sex was performed in a tertiary referral center. Cases received systemic and local therapy for HD, consisting of a rectal ointment containing 3% sucralfate and herbal extracts plus MPFF, in addition to conservative therapy, while controls received conservative therapy alone. The hemorrhoidal disease symptom score (HDSS), the Short Health Scale for HD (SHS-HD) score, and the Vaizey Incontinence Score were used to evaluate symptoms severity and their impact on quality of life and continence. Intervention requirements were assessed at baseline (T0) and after 60 days of treatment (T1). RESULTS: Between January and December 2023, a total of 98 patients were assessed for eligibility. After exclusions, 56 patients were enrolled, with 28 in each group. Significant improvements were observed in HD symptom scores from T0 to T1: the intervention group showed a mean change in HDSS of -9 [95% confidence interval (CI) -10 to -8], and the control group showed no significant change (mean change of 0; 95% CI -1.5 to 0). At T1, a higher proportion of patients in the intervention group underwent less invasive interventions compared with controls (18% versus 11%). Age, treatment group, and baseline symptom severity significantly predicted post-treatment symptom scores. CONCLUSIONS: In our study the preoperative treatment with MPFF and a sucralfate-based rectal ointment demonstrated clinical benefits in managing HD symptoms and reducing interventions. Further prospective trials are warranted to confirm and explore additional therapeutic strategies.

Suture reinforcement using a modified cyanoacrylate glue to prevent anastomotic leak in colorectal surgery: a prospective multicentre randomized trial : The Rectal Anastomotic seaL (ReAL) trial.

BACKGROUND: Anastomotic leakage (AL) is the most frequent life-threating complication following colorectal surgery. Several attempts have been made to prevent AL. This prospective, randomized, multicentre trial aimed to evaluate the safety and efficacy of nebulised modified cyanoacrylate in preventing AL after rectal surgery. METHODS: Patients submitted to colorectal surgery for carcinoma of the high-medium rectum across five high-volume centres between June 2021 and January 2023 entered the study and were randomized into group A (anastomotic reinforcement with cyanoacrylate) and group B (no reinforcement) and followed up for 30 days. Anastomotic reinforcement was performed via nebulisation of 1 mL of a modified cyanoacrylate glue. Preoperative features and intraoperative and postoperative results were recorded and compared. The study was registered at ClinicalTrials.gov (ID number NCT03941938). RESULTS: Out of 152 patients, 133 (control group, n = 72; cyanoacrylate group, n = 61) completed the follow-up. ALs were detected in nine patients (12.5%) in the control group (four grade B and five grade C) and in four patients (6.6%), in the cyanoacrylate group (three grade B and one grade C); however, despite this trend, the differences were not statistically significant (p = 0.36). However, Clavien-Dindo complications grade > 2 were significantly higher in the control group (12.5% vs. 3.3%, p = 0.04). No adverse effects related to the glue application were reported. CONCLUSION: The role of modified cyanoacrylate application in AL prevention remains unclear. However its use to seal colorectal anastomoses is safe and could help to reduce severe postoperative complications.

The management of low trans-sphincteric anal fistula during the COVID-19 pandemic: revisiting the role of the seton.

The management of trans-sphincteric anal fistula (TAF) includes several surgical options; however, during the COVID-19 pandemic, the access to the operating rooms was severely limited, leaving only the choice of minimally invasive procedures. This study aimed to evaluate the safety and effectiveness of the slow cutting seton technique for TAF performed in an outpatient setting during the COVID-19 pandemic.Patients treated for TAF between January 2020 and July 2022 and followed-up for at least 12 months were retrospectively evaluated. A vascular silicone tie used as seton was positioned in the fistula tract using a Lockhart-Mummery fistula probe. The seton was maintained in moderate tension until the sphincter muscle was passed. Percentage and time for healing, recurrence, SF-36, VAS and Vaizey's Score were recorded.Fifty-eight patients [36 male/22 female, median age 56.5 years (IQR 41.25-65.75) [with TAF were included. After a median time of 4 months, complete healing occurred in 53 cases (91.5%), the anal pain VAS decreased from 6 to 0, the anal incontinence scores did not change significantly and the QoL improved significantly in all the SF36 domains. No complications were recorded, but the fistula recurred in five cases (8.5%). Two of them had additional seton treatment, and three underwent other surgical procedures after the COVID-19 emergency.The slow cutting seton technique is a safe and effective treatment for outpatient procedure with minimal patient discomfort. This treatment option in healthcare delivery for TAF should be reconsidered, even outside the limited in-hospital access during the COVID-19 pandemic.

Safety and efficacy of Levorag emulgel in the treatment of anal fissures using a validated scoring system.

Introduction: Anal fissure is one of the most common anal disease characterized by intense anal pain, and deterioration of patients quality of life. Treatment is mainly based on the topical administration of calcium antagonist or nitric oxide ointments, and in cases refractory to medical treatment patients can undergo surgery. This study aims to assess the efficacy and safety of Levorag emulgel in the treatment of acute and chronic fissures using of a validated scoring system. Material and Methods: A prospective observational study was carried out on patients with anal fissures between February and May 2022. The efficacy of the treatment was evaluated using the REALISE score, a new validated scoring system that rates VAS for pain, NSAID use, pain duration, bleeding, and quality of life (QoL), recorded after 10, 20 and 30 days from the beginning of treatment. Results: Forty patients (median age 46 years, IQR 29-57, 70% women) with acute (22, 55%) or chronic (18, 45%) anal fissures entered the study. The median anal pain score according to the VAS scale decreased significantly from 7 (IQR 4.7-8) at baseline to 1 (IQR 0-3.2, p = 0.05) after 20 days. At the 30-day proctological examination, 22 patients (61%) were pain free (median VAS of 0, IQR 0-1.2, p < 0.05). Pain duration after defecation measured according to the REALISE score, showed a significant decrease after 10 days, from a median value of 2 (IQR 1-4) to 1 (IQR 1-1.2) (p < 0.005). The median value of the REALISE score decreased significantly, from 15 (IQR 11-19.25) at first proctological evaluation to 4 (IQR 4-6, p = 0.139) after 30 days of treatment. At day 30, complete fissure healing was achieved in 30 patients (80%). The healing rate was 82% and 78% in patients with acute and chronic anal fissures, respectively. Conclusion: The use of Levorag® Emulgel may represent a safe and effective non-invasive first line treatment in patients affected by acute or chronic anal fissure.

Retrospective comparison of long-term ten-day/month rifaximin or mesalazine in prevention of relapse in acute diverticulitis.

OBJECTIVE: Diverticular disease (DD) of the colon has an increasing burden on health services. The effectiveness of rifaximin for the treatment of DD, is not yet established. The aim of this study is to assess the impact of long-term treatment with rifaximin or mesalazine in a 10-day schedule for the prevention of recurrent diverticulitis. PATIENTS AND METHODS: This is a retrospective study. We identified all consecutive patients with DD and previous acute diverticulitis (AD) in our outpatients' database; 124 patients, were included. The recommended therapy consisted of a ten-day/month treatment with either rifaximin (400 mg bid), or mesalazine (2.4 g/daily). Primary end point was AD recurrence. RESULTS: Between 2010 and 2014, 72 patients were treated with rifaximin and 52 with mesalazine. During a median follow-up of 15 months (range 1-50), we observed 21 episodes of AD among users of either rifaximin (n=7; 0.54 per 100 person-months), or mesalazine group (n=14; 1.46 per 100 person-months). Kaplan-Meier survival estimates of recurrent AD significantly differed between rifaximin and mesalazine groups (p=0.015). The multivariate Cox regression analysis showed that AD recurrence was significantly associated with therapy (rifaximin vs. mesalazine, adjusted HR 0.27; 95% CI: 0.10 to 0.72), age and gender. CONCLUSIONS: Long-term treatment with rifaximin in a 10-day schedule appears more effective than mesalazine in preventing recurrent AD.

Adaptation to nicotine feeding in Myzus persicae.

Lineages of the generalist hemipteran herbivore Myzus persicae (green peach aphid) that have expanded their host range to include tobacco often have elevated nicotine tolerance. The tobacco-adapted M. persicae lineage used in this study was able to reproduce on nicotine-containing artificial diets at concentrations that were 15-fold higher than those that were lethal to a non-adapted M. persicae lineage. Fecundity of the nicotine-tolerant M. persicae lineage was increased by 100 µM nicotine in artificial diet, suggesting that this otherwise toxic alkaloid can serve as a feeding stimulant at low concentrations. This lineage also was pre-adapted to growth on tobacco, exhibiting no drop in fecundity when it was moved onto tobacco from a different host plant. Although growth of the non-tobacco-adapted M. persicae lineage improved after three generations on tobacco, this higher reproductive rate was not associated with increased nicotine tolerance. Myzus persicae gene expression microarrays were used to identify transcripts that are up-regulated in response to nicotine in the tobacco-adapted lineage. Induced expression was found for CYP6CY3, which detoxifies nicotine in M. persicae, other genes encoding known classes of detoxifying enzymes, and genes encoding secreted M. persicae salivary proteins.

Suppression of plant defenses by a Myzus persicae (green peach aphid) salivary effector protein.

The complex interactions between aphids and their host plant are species-specific and involve multiple layers of recognition and defense. Aphid salivary proteins, which are released into the plant during phloem feeding, are a likely mediator of these interactions. In an approach to identify aphid effectors that facilitate feeding from host plants, eleven Myzus persicae (green peach aphid) salivary proteins and the GroEL protein of Buchnera aphidicola, a bacterial endosymbiont of this aphid species, were expressed transiently in Nicotiana tabacum (tobacco). Whereas two salivary proteins increased aphid reproduction, expression of three other aphid proteins and GroEL significantly decreased aphid reproduction on N. tabacum. These effects were recapitulated in stable transgenic Arabidopsis thaliana plants. Further experiments with A. thaliana expressing Mp55, a salivary protein that increased aphid reproduction, showed lower accumulation of 4-methoxyindol-3-ylmethylglucosinolate, callose and hydrogen peroxide in response to aphid feeding. Mp55-expressing plants also were more attractive for aphids in choice assays. Silencing Mp55 gene expression in M. persicae using RNA interference approaches reduced aphid reproduction on N. tabacum, A. thaliana, and N. benthamiana. Together, these results demonstrate a role for Mp55, a protein with as-yet-unknown molecular function, in the interaction of M. persicae with its host plants.

The role of protein effectors in plant-aphid interactions.

Aphid salivary proteins, which are injected into the phloem sieve elements during feeding, play a central role in plant-aphid interactions. Among the dozens of known salivary proteins, many have no homology to proteins from other organisms. These aphid-specific proteins likely have evolved as effectors that inhibit plant defenses, prevent phloem sieve-element occlusion, and otherwise promote the unique phloem feeding style. However, aphid salivary proteins also are recognized by plants to mount defense responses and are likely a major factor in limiting the host range of particular aphid species and biotypes. Newly developed research tools provide excellent opportunities for analyzing the mostly unknown functions of aphid salivary proteins and elucidating their contribution to the complex interactions between aphids and their host plants.

Meta-analysis: long-term therapy with rifaximin in the management of uncomplicated diverticular disease.

BACKGROUND: Diverticular disease of the colon is a common gastrointestinal disease. Although most patients remain asymptomatic for their whole life, about 20-25% present symptoms related to 'diverticular disease'. Several randomised trials verified efficacy of a poorly absorbed antibiotic, such as rifaximin-α (rifaximin), in soothing symptoms and preventing diverticulitis. AIM: To evaluate the long-term efficacy administration of rifaximin plus fibre supplementation vs. fibre supplementation alone, on symptoms and complications, in patient with symptomatic uncomplicated diverticular disease. METHODS: Pertinent studies were selected from the Medline, and the Cochrane Library Databases, references from published articles and reviews. Conventional meta-analysis according to DerSimonian and Laird method was used for the pooling of the results. The outcomes were 1- year complete symptom relief, and 1- year complication incidence. The rate difference (RD, with 95% CI) and the Number Needed to Treat (NNT) were used as measure of the therapeutic effect on each outcome. RESULTS: Four prospective randomised trials including 1660 patients were selected. The pooled RD for symptom relief was 29.0% (rifaximin vs. control; 95% CI 24.5-33.6%; P<0.0001; NNT=3). The pooled RD for complication rate was -1.7% in favour of rifaximin (95% CI -3.2 to -0.1%; P=0.03; NNT=59). When considering only acute diverticulitis, the pooled RD in the treatment group was -2% (95% CI -3.4 to -0.6%; P=0.0057; NNT=50). CONCLUSIONS: In symptomatic uncomplicated diverticular disease, treatment with rifaximin plus fibre supplementation is effective in obtaining symptom relief and preventing complications at 1 year.

A distinct DGAT with sn-3 acetyltransferase activity that synthesizes unusual, reduced-viscosity oils in Euonymus and transgenic seeds.

Endosperm and embryo tissues from the seeds of Euonymus alatus (Burning Bush) accumulate high levels of 3-acetyl-1,2-diacyl-sn-glycerols (acTAGs) as their major storage lipids. In contrast, the aril tissue surrounding the seed produces long-chain triacylglycerols (lcTAGs) typical of most other organisms. The presence of the sn-3 acetyl group imparts acTAGs with different physical and chemical properties, such as a 30% reduction in viscosity, compared to lcTAGs. Comparative transcriptome analysis of developing endosperm and aril tissues using pyrosequencing technology was performed to isolate the enzyme necessary for the synthesis of acTAGs. An uncharacterized membrane-bound O-acyltransferase (MBOAT) family member was the most abundant acyltransferase in the endosperm but was absent from the aril. Expression of this MBOAT in yeast resulted in the accumulation of acTAGs but not lcTAG; hence, the enzyme was named EaDAcT (Euonymus alatus diacylglycerol acetyltransferase). Yeast microsomes expressing EaDAcT possessed acetyl-CoA diacylglycerol acetyltransferase activity but lacked long-chain acyl-CoA diacylglycerol acyltransferase activity. Expression of EaDAcT under the control of a strong, seed-specific promoter in Arabidopsis resulted in the accumulation of acTAGs, up to 40 mol % of total TAG in the seed oil. These results demonstrate the utility of deep transcriptional profiling with multiple tissues as a gene discovery strategy for low-abundance proteins. They also show that EaDAcT is the acetyltransferase necessary and sufficient for the production of acTAGs in Euonymus seeds, and that this activity can be introduced into the seeds of other plants, allowing the evaluation of these unusual TAGs for biofuel and other applications.

Cutaneous neoplasm arising from total knee replacement incision in the early postoperative period.

Potential wound healing complications after total knee arthroplasty includes infection, skin edge necrosis, and dehiscence. We report another type of wound problem: the rapid development of a skin malignancy (or premalignancy) along an immature scar after knee arthroplasty.

Prevention of non-steroidal anti-inflammatory drug-induced gastrointestinal mucosal injury: risk factors for serious complications.

BACKGROUND: 1-2% of all patients under non-steroidal anti-inflammatory drug therapy are exposed to serious upper gastrointestinal complications. The policy of prevention of non-steroidal anti-inflammatory drug-induced gastrointestinal mucosal injury by using misoprostol or suppressing acid secretion is still a matter of debate. AIMS: To discuss the effectiveness of prophylaxis of a gastrointestinal complication during non-steroidal anti-inflammatory drug treatment, according to the number and relevance of risk factors. PATIENTS: A total of 8.843 patients with rheumatoid arthritis, admitted to the widest prospective multicentre mega-trial, on 6-month complication prevention of non-steroidal anti-inflammatory drug-induced ulcers. METHODS: The results are presented in terms of the number of patients to be treated (number needed to treat) in order to prevent one serious upper gastrointestinal complication, and corrected for the number of patients, that receiving the prophylaxis therapy, would lead to one additional withdrawal (number needed to harm). RESULTS: The base-line risk for a complication strongly depended on the number and relevance of risk factors: history of peptic ulcer disease, of gastrointestinal bleeding, of cardiovascular disease, and age. In the general study population, the relative risk reduction of gastrointestinal complications with misoprostol was 40%: thus the number needed to treat to prevent 1 event was 250 in the experimental period (6 months) or 125 when normalized at one-year treatment (1 year number needed to treat]. When considering the prophylaxis gain in intermediate (risk 1-2%) or high risk subjects (patients with a probability of an event over 2%, for the presence of 1 important risk factor or multiple factors), the 1-year number needed to treat rapidly drops from about 100 to about 17. The number needed to harm for one withdrawal was 18. The number needed to treat corrected for withdrawals in order to avoid major complications rises from 125 to 132 in the general population of non-steroidal anti-inflammatory drug users; from 102 to 105 in subjects at intermediate risk, such as patients with history of cardiovascular disease; in the groups at high risk, from 26 to 27 (patients with history of peptic ulcer disease), and from 16 to 17 (patients with history of peptic ulcer disease, cardiovascular disease and aged over 65 years). CONCLUSIONS: Patients at intermediate and high risk for complications from non-steroidal anti-inflammatory drug-induced ulcers should be considered for prophylaxis. In this group of patients, misoprostol prevention of severe complications is effective, and its clinical relevance similar to that of other preventive measures in medical practice.

Prevention of nonsteroidal anti-inflammatory drug-induced gastrointestinal mucosal injury. A meta-analysis of randomized controlled clinical trials.

BACKGROUND: The policy of prevention of nonsteroidal anti-inflammatory drug (NSAID)-induced gastrointestinal mucosal injury is still a matter of discussion. Indeed, no consensus exists as to whether cotherapy with histamine type 2 (H2) blockers or misoprostol is cost-effective. METHODS: Placebo-controlled randomized clinical trials on the use of H2 blockers or misoprostol, as preventive agents (published between) January 1970 and December 1994), were identified through MEDLINE and reference lists from literature reviews. Crude rates of endoscopic lesions with short-term (< 2 weeks) and long-term (> 4 weeks) NSAID treatment were systematically assessed by 3 independent observers based on the intention-to-treat principle. The method of DerSimonian and Laird was used for pooling data. Heterogeneity was evaluated by using the Q statistic and the plots described by L'Abbe and colleagues. RESULTS: Twenty-four trials met the criteria for entry into the study. Gastric ulcer was found to be significantly reduced by misoprostol-both in short-term (pooled rate difference [RD], -13%, 95% confidence interval [CI], -26% to -1%) and long-term (RD, -8%; 95% CI, -18% to -1%) NSAID treatment-but not by H2 blockers. The risk for duodenal ulcer was significantly reduced by H2 blockers (RD, -2%; 95% CI, -5% to -0.2%) and by misoprostol (RD, -3%; 95% CI, -6% to -0.1%) in long-term but not in short-term administration. CONCLUSIONS: The use of misoprostol, but no that of H2 blockers, was beneficial in the prevention of NSAID-induced gastric ulcers. The number of patients to be treated to prevent 1 gastric ulcer with short- and long-term NSAID treatment is 11 and 15, respectively, for an intermediate baseline risk of 10%. Misoprostol and H2 blockers were beneficial in the long-term prevention of duodenal ulcers; misoprostol or H2 blockers in the short-term prevention of duodenal ulcers remains to be confirmed.

Effects of sulglycotide on inflammation and epithelial cell turnover in active Helicobacter pylori+ chronic gastritis. A pilot study.

The effects of Sulglycotide were evaluated in a pilot study of active H. pylori+ atrophic gastritis. Ten informed patients (mean age 51 +/- 13 years) entered a double-blind study. Five received Sulglycotide 400 mg three times a day for one year, the other 5, placebo. At 0, 30, 90, 270, and 360 days of treatment, patients underwent endoscopic examinations with multiple biopsies. Morphometric studies (number of inflammatory cells and percent gland volume), morphologic studies (according to the Sydney system), and flow cytofluorimetry were performed in all cases. Compared to findings in the placebo group, patients treated with Sulglycotide showed a reduced number of inflammatory cells and an increase in gland volume 120 days after treatment. While the difference was not statistically significant, the trend was confirmed by the morphologic patterns. Flow cytofluorimetry revealed an increase in the percentage of cells in the G2 phase (full maturation) and a parallel drop in the S phase (premitotic synthesis) in the Sulglycotide group only in the first three months. These data would appear to indicate an acceleration of gastric epithelial cell maturation and a decrease in the inflammatory infiltrate under the effect of Sulglycotide.

Prevention of NSAID-induced gastroduodenal mucosal injury: meta-analysis of clinical trials with misoprostol and H2-receptor antagonists.

In order to provide a systematic overview of the available information on the prevention of nonsteroidal anti-inflammatory drug (NSAID)-induced gastrointestinal mucosal injury, we performed a meta-analysis based on all the in extenso published randomized clinical trials comparing H2-blockers or misoprostol to placebo for the prevention of NSAID-induced gastrointestinal mucosal injury in arthritis patients or normal subjects. The main endpoints after NSAID therapy were considered the number of subjects developing gastric ulcer, or clinically relevant gastric lesions (i.e. more than 10 erosions or 1 ulcer), or duodenal ulcer, or clinically relevant duodenal lesions (i.e. more than 10 erosions or 1 ulcer). The total number of patients studied was 1,955, and that of normal subjects was 715. Results were analyzed by the DerSimonian and Laird method, as well as by the Peto one. The data available from the trials suggest that misoprostol prevention is of benefit in patients under NSAID treatment for the prevention of NSAID-induced gastroduodenal mucosal injury. The effect of prevention is statistically significant with both methods, and ranges from -42% (duodenal ulcer) to -79% (gastric ulcer). The prevention estimates for gastric and duodenal erosions are in between. H2-blockers seem to be less effective: prevention is not indeed demonstrable for the more relevant lesions, like gastric and duodenal ulcer.

Gastroduodenal toxicity of different nonsteroidal antiinflammatory drugs.

Although the etiologic relation between nonsteroidal antiinflammatory drug (NSAID) use and gastrointestinal lesions is well documented, newly introduced NSAIDs deserve a fresh examination for their risk/benefit ratio. To estimate the association between consumption of ketorolac and the occurrence of gastroduodenal lesions, we conducted a case-control study. The study population comprised 600 outpatients with a confirmed endoscopic diagnosis of ulcer and erosion in 1991 and 1992 and 6,000 community controls matched by age and sex. We retrieved the prescription history through a computerized prescription monitoring system. We defined exposure to each study drug as "current" (month of endoscopy and preceding month), "recent" (second or third month preceding endoscopy). and "past" (fourth to sixth month preceding endoscopy). Current users of NSAIDs showed a 30% increase in the incidence of gastroduodenal lesions [odds ratio (OR) = 1.3; 95% confidence interval (CI) = 0.98 - 1.8] after adjustment for recent or past use of any NSAID, recent or past gastrotoxic therapy, recent or past use of gastroprotective drugs, and recent or past use of any other drug. Among NSAIDs, ketorolac was the only one showing a distinctly elevated risk of gastroduodenal lesions (OR = 4.2; 95% CI = 1.9-9.4). Current use of any NSAID was associated with almost a doubling of risk for ulcer alone (OR = 1.9; 95% CI = 1.3-3.0); no elevation in risk was found for erosions. The adjusted relative risk for ulcer associated with current use of ketorolac was 9.8 (95% CI = 3.4-28.10. Recent and past use of NSAIDs does not increase the risk of ulcer.(ABSTRACT TRUNCATED AT 250 WORDS)