Is chemodenervation with incobotulinumtoxinA an alternative to invasive chronic anal fissure treatments?

BACKGROUND: Botulinum toxin type A is currently strongly recommended for the treatment of anal fissures (AFs). However, there is still no consensus on dosage or injection technique. This study provides further efficacy and safety evidence in a 2-year follow-up. METHOD: Prospective, open-label, single-arm, single-center study carried out in adult patients with AFs non-responsive to previous treatments. Patients were treated with incobotulinumtoxinA (incoBoNT/A) injected in both laterals and posterior intersphincteric groove. Healing rate at 2 years was the primary endpoint. Secondary endpoints included internal anal sphincter pressures, incontinence, and safety. RESULTS: A total of 49 patients were treated with a mean incoBoNT/A dose of 40.5 U (spread across three locations). Healing rate at 2 years was 83.9% with a 24.5% of recurrence throughout the study. Only 7 patients (14.3%) reported adverse events (AEs) that were mild and temporary. Mean reduction in anal resting pressure was -9.1 mmHg at 3 months (p = 0.001). Mean reduction in voluntary squeeze pressure was -27.5 mmHg at 3 months (p < 0.001). Mean pain perception measured with a visual analog scale decreased by -6.5 points at 2 years (p < 0.001). There was an incontinence increase at 1 month of 1.3 points (p = 0.006), but baseline values were restored at 6 months. CONCLUSION: We present results that support the use of incoBoNT/A as a second line for AFs that do not respond to ointment therapy. IncoBoNT/A injection is a less invasive treatment that should be considered before surgery due to its efficacy and its safety which includes no permanent impairment. TRIAL REGISTRATION: ISRCTN90354265; Registered on 16th February 2024. Retrospectively registered.

Ustekinumab as induction and maintenance therapy for ulcerative colitis - national extended follow-up and a review of the literature.

INTRODUCTION: Ustekinumab use in ulcerative colitis had shown low adverse event and high persistence rates to 3 years via the UNIFI long-term extension study. Outcomes beyond 3 years have not been previously described. We describe the safety signals of the entire UNIFI Australian population beyond 3 years. METHODS: This retrospective multicenter observational cohort study recruited from all Australian UNIFI centers. The primary outcome was safety via adverse events. Secondary outcomes included the clinical relapse rate on ustekinumab, and the need to switch from ustekinumab to an alternate agent. RESULTS: There were 14 patients [11 male, mean age 47 (±14) years], with a median diagnosis of 10.8 (±4.5) years prior to UNIFI enrollment. Median follow-up was 298 weeks (5.7 years) (Interquartile range (IQR): 220-311 weeks). Within the long-term extension, there were three serious adverse events and one minor event. 42.9% (6/14) patients had clinical relapses, of which clinical remission was recaptured in 83.3% (5/6). 85.7% (12/14) persisted on ustekinumab in the long-term, with 7.1% (1/14) electively ceasing ustekinumab and 7.1% (1/14) changed from ustekinumab due to clinical relapse. CONCLUSION: For moderate-to-severe UC in Australia, ustekinumab maintained efficacy beyond 3 years with a high persistence rate and no new safety signals. TRIAL REGISTRATION: The trial is registered at ANZCTR (identifier: ACTRN12622001332718).

Atypical histological presentation of bone regeneration after insertion of cryoprotected allogeneic bone graft.

BACKGROUND: To evaluate bone regenerative capacity of cryoprotected corticocancellous allogeneic bone graft performed in type II and III post-extraction sockets for ridge preservation after twelve weeks in-vivo. MATERIAL AND METHODS: Twenty-seven type II or III bony-walled extraction sockets (mandible and maxilla) were selected for this study. Following atraumatic tooth-extraction a cryoprotected corticocancellous allogeneic bone graft material and a resorbable porcine-derived collagen membrane were used for ridge preservation. During re-entry surgery at approximately 12 weeks, bone core biopsies were obtained using a 3.2 mm trephine drill and samples were histologically processed and subjected to qualitative and quantitative histomorphometric analysis. Quantitative data was analyzed using a general linear mixed model with results presented as mean values with the corresponding 95% confidence interval values. RESULTS: Healing without incident and ridge preservation allowed for the placement of dental implants after 12 weeks in 25 out of the 27 treated socket sites. Analyses yielded an average of ~21.0±7% of old/native bone, ~17±5.5% of newly regenerated bone (total of ~38±12.8% for all bone), 0.23±0.14% of new bone presenting with nucleating sites within the matrix, ~52±5.12% of soft tissue, and 3.6±2.09% of damaged bone. The average regenerated bone was statistically analogous to that of old/native bone (p=0.355). Furthermore, an atypical histological pattern of bone regeneration was observed, with newly formed bone exhibiting "infiltration-like" behavior and with new bone nucleating sites observed within the demineralized bone matrix. CONCLUSIONS: Cryoprotected corticocancellous allogeneic bone-graft demonstrated osteoconductive, osteoinductive, and osteogenic properties, yielding unique healing patterns which does warrant further investigation.

Antioxidant activity of glucosamine and its effects on ROS production, Nrf2, and O-GlcNAc expression in HMEC-1 cells.

Glucosamine (GlcN) is the most used supplement for osteoarthritis treatment. In vitro studies have related GlcN to beneficial and detrimental effects on health. The aim of this study was to evaluate the effects of O-linked-N-acetylglucosaminylation (O-GlcNAc) on GlcN-induced ROS production and Nrf2 expression in human dermal microvascular endothelial cells-1 (HMEC-1) and to evaluate the antioxidant capacity of GlcN compared to well-known antioxidants. For this, we evaluate the antioxidant capacity by in vitro assays. Besides, the GlcN (5-20 mM) effects on cell viability, reactive oxygen species (ROS) production, O-GlcNAc, and nuclear factor erythroid-2-related factor 2 (Nrf2) expression with and without the O-GlcNAc inhibitor OSMI-1 (10 µM) in HMEC-1 were evaluated. GlcN showed high inhibitory concentration (low scavenging activity) against superoxide (O2•─, IC20 = 47.67 mM), 2,2-diphenyl-1-picrylhydrazyl (DPPH•, IC50 = 21.32 mM), and hydroxyl (HO•, IC50 = 14.04 mM) radicals without scavenging activity against hydrogen peroxide (H2O2) and low antioxidant capacity determined by oxygen radical absorbance capacity (ORAC, 0.001 mM Trolox equivalent) and ferric reducing antioxidant power (FRAP, 0.046 mM Trolox equivalent). In cell culture, GlcN (20 mM) reduced cell viability up to 26 % and induced an increase in ROS production (up to 70 %), O-GlcNAc (4-fold-higher vs. control), and Nrf2 expression (56 %), which were prevented by OSMI-1. These data suggest an association between O-GlcNAc, ROS production, and Nrf2 expression in HMEC-1 cells stimulated with GlcN.

Antibacterial activity of Thymus vulgaris (thyme) essential oil against strains of Pseudomonas aeruginosa, Klebsiella pneumoniae and Staphylococcus saprophyticus isolated from meat product.

Meat products represent an important component of the human diet and are a good source of nutrients. Food-borne microorganisms are the main pathogens that cause human diseases as a result of food consumption, especially products of animal origin. The objective of the present research was to verify the antibacterial activity of the essential oil of Thymus vulgaris against strains of Klebsiella pneumoniae, Pseudomonas aeruginosa and Staphylococcus saprophyticus isolated from meat products. For this, the analyses of Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) were performed in microdilution plates. The association of the product with antimicrobials was also studied using disk diffusion. And the anti-adherent activity, which was determined in the presence of sucrose, in glass tubes. Thyme oil showed a strong inhibitory activity against K. pneumoniae, P. aeruginosa and S. saprophyticus, with the MIC values ranging from 64 to 512 µg/mL, and bactericidal effect for most strains, with MBC values ranging from 256 to 1,024 µg/mL. T. vulgaris oil exhibited varied interactions in association with the antimicrobials, with synergistic (41.67%), indifferent (50%) and antagonistic (8.33%) effects. Regarding the anti-adherent activity, the test product was effective in inhibiting the adherence of all bacterial strains under study. Therefore, thyme oil presents itself as an antibacterial and anti-adherent agent against K. pneumoniae, P. aeruginosa and S. saprophyticus, being a natural product that can represent an interesting alternative in the efforts to combat foodborne diseases.

The percentage of CD39+ monocytes is higher in pregnant COVID-19+ patients than in nonpregnant COVID-19+ patients.

Current medical guidelines consider pregnant women with COVID-19 to be a high-risk group. Since physiological gestation downregulates the immunological response to maintain "maternal-fetal tolerance", SARS-CoV-2 infection may constitute a potentially threatening condition to both the mother and the fetus. To establish the immune profile in pregnant COVID-19+ patients, a cross-sectional study was conducted. Pregnant women with COVID-19 (P-COVID-19+; n = 15) were analyzed and compared with nonpregnant women with COVID-19 (NP-COVID-19+; n = 15) or those with physiological pregnancy (P-COVID-19-; n = 13). Serological cytokine and chemokine concentrations, leucocyte immunophenotypes, and mononuclear leucocyte responses to polyclonal stimuli were analyzed in all groups. Higher concentrations of serological TNF-α, IL-6, MIP1b and IL-4 were observed within the P-COVID-19+ group, while cytokines and chemokines secreted by peripheral leucocytes in response to LPS, IL-6 or PMA-ionomicin were similar among the groups. Immunophenotype analysis showed a lower percentage of HLA-DR+ monocytes in P-COVID-19+ than in P-COVID-19- and a higher percentage of CD39+ monocytes in P-COVID-19+ than in NP-COVID-19+. After whole blood polyclonal stimulation, similar percentages of T cells and TNF+ monocytes between groups were observed. Our results suggest that P-COVID-19+ elicits a strong inflammatory response similar to NP-COVID19+ but also displays an anti-inflammatory response that controls the ATP/adenosine balance and prevents hyperinflammatory damage in COVID-19.

Recommendations of the Society of Thoracic Surgery and the Section of Cardiothoracic and Vascular Surgery of the Spanish Society of Anesthesia, Resuscitation and Pain Therapy, for patients undergoing lung surgery included in an intensified recovery program.

In recent years, multidisciplinary programs have been implemented that include different actions during the pre, intra and postoperative period, aimed at reducing perioperative stress and therefore improving the results of patients undergoing surgical interventions. Initially, these programs were developed for colorectal surgery and from there they have been extended to other surgeries. Thoracic surgery, considered highly complex, like other surgeries with a high postoperative morbidity and mortality rate, may be one of the specialties that most benefit from the implementation of these programs. This review presents the recommendations made by different specialties involved in the perioperative care of patients who require resection of a lung tumor. Meta-analyzes, systematic reviews, randomized and non-randomized controlled studies, and retrospective studies conducted in patients undergoing this type of intervention have been taken into account in preparing the recommendations presented in this guide. The GRADE scale has been used to classify the recommendations, assessing on the one hand the level of evidence published on each specific aspect and, on the other hand, the strength of the recommendation with which the authors propose its application. The recommendations considered most important for this type of surgery are those that refer to pre-habilitation, minimization of surgical aggression, excellence in the management of perioperative pain and postoperative care aimed at providing rapid postoperative rehabilitation.

Microbial contamination on ambulance surfaces: a systematic literature review.

Healthcare-associated infections (HAIs) are infections that patients acquire while receiving medical treatment in a healthcare facility. During ambulatory transport, the patient may be exposed to pathogens transmitted from emergency medical service (EMS) personnel or EMS surfaces.The aim of this study was to determine whether organisms commonly associated with HAIs have been detected on surfaces in the patient-care compartment of ambulances. Five electronic databases - PubMed, Scopus, Web of Science, Embase and Google Scholar were used to search for articles using inclusion and exclusion criteria following the PRISMA checklist. Inclusion criteria consisted of articles published in English, between 2009 and 2020, had positive samples collected from the patient-care compartment of a ground ambulance, and reported sample collection methods of either swab sampling and/or Replicate Organism Detection and Counting (RODAC) contact plates. Studies not meeting these criteria were excluded from this review. From a total of 1376 articles identified, 16 were included in the review. Organisms associated with HAIs were commonly detected in the patient-care compartment of ambulances across a variety of different surfaces, including blood pressure cuffs, oxygen apparatuses, and areas of patient stretchers. A high prevalence of pathogenic bacteria in ambulances suggests that standard protocols related to cleaning compliance may not be effective. The primary recommendation is that designated subject matter experts in infection prevention should be incorporated as liaisons in the pre-hospital setting, acting as a link between the pre-hospital (e.g., ambulance transport) and hospital environments.