Universal Guidelines Research Articles

Toward Ending the HIV Epidemic: Temporal Trends and Disparities in Early ART Initiation and Early Viral Suppression Among People Newly Entering HIV Care in the United States, 2012-2018.

In 2012, the US Department of Health and Human Services updated their HIV treatment guidelines to recommend antiretroviral therapy (ART) for all people with HIV (PWH) regardless of CD4 count. We investigated recent trends and disparities in early receipt of ART prescription and subsequent viral suppression (VS). We examined data from ART-naïve PWH newly presenting to HIV care at 13 North American AIDS Cohort Collaboration on Research and Design clinical cohorts in the United States during 2012-2018. We calculated the cumulative incidence of early ART (within 30 days of entry into care) and early VS (within 6 months of ART initiation) using the Kaplan-Meier survival function. Discrete time-to-event models were fit to estimate unadjusted and adjusted associations of early ART and VS with sociodemographic and clinical factors. Among 11 853 eligible ART-naïve PWH, the cumulative incidence of early ART increased from 42% in 2012 to 82% in 2018. The cumulative incidence of early VS among the 8613 PWH who initiated ART increased from 83% in 2012 to 93% in 2018. In multivariable models, factors independently associated with delayed ART and VS included non-Hispanic/Latino Black race, residence in the South census region, being a male with injection drug use acquisition risk, and history of substance use disorder (SUD; all P ≤ .05). Early ART initiation and VS have substantially improved in the United States since the release of universal treatment guidelines. Disparities by factors related to social determinants of health and SUD demand focused attention on and services for some subpopulations.

Improving genetic diagnosis by disease-specific, ACMG/AMP variant interpretation guidelines for hearing loss

The 2018 Hearing Loss Expert Panel (HL-EP)-specific guidelines specified from the universal 2015 ACMG/AMP guidelines are proposed to be used in genetic HL, which prompted this study. A genetic HL cohort comprising 135 unrelated probands with available exome sequencing data was established. Overall, 169 variants were prioritized as candidates and interpreted using the 2015 ACMG/AMP and 2018 HL-EP guidelines. Changes in rule application and variant classification between the guidelines were compared. The concordance rate of variant classification of each variant between the guidelines was 71.60%, with significant difference. The proportion of pathogenic variants increased from 13.02% (2015) to 29.59% (2018). Variant classifications of autosomal recessive (AR) variants that previously belonged to VUS or likely pathogenic in the 2015 guidelines were changed toward pathogenic in the 2018 guidelines more frequently than those of autosomal dominant variants (29.17% vs. 6.38%, P = 0.005). Stratification of the PM3 and PP1 rules in the 2018 guidelines led to more substantial escalation than that in the 2015 guidelines. We compared the disease-specific guidelines (2018) with the universal guidelines (2015) using real-world data. Owing to the sophistication of case-level data, the HL-specific guidelines have more explicitly classified AR variants toward “likely pathogenic” or “pathogenic”, serving as potential references for other recessive genetic diseases.

Increasing lipid screenings in children 9–11 years old at a federally qualified health center - A quality improvement project

BackgroundCoronary artery disease (CAD) remains the leading cause of death in the U.S. Atherosclerotic changes leading to CAD begin in early childhood. Universal lipid screenings remain low nationwide despite the 2011 National Heart, Lung, and Blood Institute's (NHLBI) Expert Panel Guidelines. Local problemThe aim of this quality improvement project was to examine the benefit of an educational intervention on the implementation of universal lipid screening guidelines within a federally qualified health center tasked with providing care to a high-risk population. InterventionAn educational intervention was offered detailing the 2011 NHLBI guidelines. A total of seven medical providers participated in the intervention. MethodFollowing the intervention, a pre- and post- knowledge survey was given to assess improvement in knowledge. A retrospective chart review was performed to evaluate application to practice. ResultsThe number of lipid screenings improved from 7.8% (n = 384) pre-intervention to 39.2% (n = 74) post intervention. There was a statistically significant increase in screenings post-intervention t (456) = 7.842, p = .000, two-tailed). ConclusionMore studies are needed to adequately identify the impact of universal screening guidelines on the health of both children and adults alike. Practice implicationsUniversal lipid screenings remain promising in early identification of CAD in the pediatric population. Interventions related to expanding the knowledge of healthcare providers, patients, and families are key to decreasing CAD morbidity and mortality.

The Consistency Between the Chinese Essential Medicines List and Treatment Guidelines-Taking Oncology Medicines as an Example.

The concepts of “essential medicine” and “national medicine policy” were first put forward for the first time at the World Health Assembly in 1975 in an effort to alleviate the problem of medicine unavailability in developing and poor countries. The essential medicine system in China has experienced three development stages since 1979, when the concept of essential medicines was first introduced, to actively respond to the call of the World Health Organization. Currently, the essential medicines list published in China is the national essential medicines list (2018 Edition). In this study, we examined the consistency between the essential medicines for treating seven cancers (liver cancer, breast cancer, esophageal cancer, lung cancer, colorectal cancer, gastric cancer, and leukemia) and the recommended medicines by cancer treatment guidelines to determine whether the essential medicines are of high quality for clinical needs. The results indicated that the degree of similarity between oncology medicines on the essential medicines list and oncology medicines recommended by guidelines was low, with the majority falling between 30 and 60%. Therefore, to improve the quality of essential medicines, it is necessary to further improve the matching degree. In addition, to further improve the consistency between the essential medicines list and treatment guidelines, the following suggestions are put forward in this paper: (1). Formulate universal treatment guidelines; (2). When selecting essential medicines, greater consideration should be given to those recommended in the guidelines; (3). The essential medicines list and treatment guidelines should be concurrently updated; (4). The cycle for updating the essential medicines list and treatment guidelines should be shortened.

터치스크린 키오스크의 유니버설 설계 지침 개발: 화면 크기 및 화면설계요소를 중심으로

Objective: This study aims to develop universal design guidelines for touchscreen kiosks that can be comfortably used by various users such as wheelchair patients and elderly people.<BR><BR>Background: The use of touchscreen kiosks in customer service has been increased; however, various usability problems with the kiosk have been reported.<BR><BR>Method: A literature survey and expert review were conducted to draft the universal design guidelines for touchscreen kiosks; then, a prototype of the kiosk for a fast-food restaurant was built by applying the design guidelines, and its usability was evaluated by comparing it with an original interface for the kiosk of that restaurant.<BR><BR>Results: The revised kiosk design showed better usability than the original design regarding performance time, number of screen touching, number of mistakes and errors, task success rate, and subjective satisfaction.<BR><BR>Conclusion: The universal design guidelines for touchscreen kiosks are proposed based on the results of the usability evaluation conducted in this study.<BR><BR>Application: The proposed design guideline can be applied to the development of various touchscreen kiosks providing good usability to a wide range of users including wheelchair patients, elderly people, and children.

Chest Compressions in Pediatric Patients With Continuous-Flow Ventricular Assist Devices: Case Series and Proposed Algorithm.

Patients with continuous flow ventricular assist devices (CF-VAD's) in the systemic ventricle (left ventricle or single ventricle) often have no palpable pulses, unreliable pulse oximetry waveforms and non-pulsatile arterial waveforms despite hemodynamic stability. When circulatory decompensation occurs, standard indicators to begin cardiopulmonary resuscitation (CPR) which are used in other pediatric patients (i.e., significant bradycardia or loss of pulse) cannot be applied in the same fashion. In this population, there may already be pulselessness and development of bradycardia in and of itself would not trigger chest compressions. There are no universal guidelines to dictate when to consider chest compressions in this population. As such, there may be a delay in decision-making or in recognizing the need for chest compressions, even in patients hospitalized in intensive care units (ICU) and cared for by experienced staff who perform CPR regularly. We present four examples of pediatric cardiac ICU patients from a single center who underwent CPR between 2018 and 2019. Based on this case series, we propose a decision-making algorithm for chest compressions in pediatric patients with CF-VADs in the systemic ventricle.

Akut appendicitis kivizsgálásának és kezelésének összehasonlítása sebészeti osztályunkon a COVID-19-pandémia előtti időszak és a pandémia III. hulláma alatt.

Introduction. Appendicitis is one of the most common causes of acute abdominal surgical indications. WHO declared the SARS-CoV-2 (COVID-19) virus infection apandemic on the 11.03.2020., affecting all segments of healthcare. Management of the acute cases also faced new challenges as aresult of the restrictive measures taken during the pandemic, affecting the population and healthcare providers. In our surgical department, during the medical care of those diagnosed with acute appendicitis, in the absence of uniform professional protocols, we often required individual considerations. In the absence of universal professional guidelines, during the medical care of those who had been diagnosed with acute appendicitis we often required individual considerations in our surgical department. Aim. the comparison of the time elapsed between the onset of the symptoms and the time the patients arrived to our surgical department, the frequency of hospitalisation and the frequency and difference between postoperative complications in patients diagnosed with acute appendicitis during the pre-pandemic period of SARS-CoV-2 and the III. wave of COVID-19. Methods. in our retrospective analysis we included those more than 18-years old patients who were diagnosed with the clinic-radiological picture of acute appendicitis during the pre-pandemic 6 months (16. 09. 2019. – 16. 03. 2020.) and the III. wave of COVID-19 (01. 11. 2020. – 01. 04. 2021.). We compared the length of time between the onset of symptoms and the beginning of hospitalisation, the complexity of appendicitis, the method of surgery used, the duration of hospitalisation and the development of postoperative complications. Statistical significance was examined byt-test and Fischer-test. Results. 64 patients were included, 47 in the pre-pandemic period and 17 in the III. wave of COVID-19. During the pandemic, the number of people diagnosed with acute appendicitis showed adeclining trend, however the incidence of complicated appendicitis increased (26% « 35%). In the III. wave of COVID-19, the time between the onset of symptoms and the examination was 27,3 h longer on average (P= 0.275), the hospitalisation was 17.3 h longer (P= 0.412) and the postoperative complications (2.12% « 23.5%) and surgical conversions (0% « 21%) were also significantly different (P= 0.264), but there was no significant correlation in either case. Conclusion. although there was no significant correlation in our analysis, it appears that during the pandemic, patients sought medical attention later and with more severe symptoms, resulting in progression of acute appendicitis.

Developing a clinical care pathway to reduce and treat enteric feeding tube site skin excoriation: a quality-improvement pilot study

Skin excoriation is a common complication of enteral tube feeding; however, universal guidelines for treatment do not exist. A quality improvement pilot study to inform the development of a local clinical care pathway was conducted. The enteral nutrition team identified products and assessed patient preference, ease of use, availability, and clinical outcomes for inclusion. This pathway includes gentle site cleansing followed by skin protectant application. For mild skin excoriation (<5 mm), acrylate terpolymer barrier film (3M Cavilon No Sting Barrier Film) was applied once every seven days. Moderate skin excoriation (5-20 mm) received acrylate terpolymer barrier film twice a day for seven days. Severe skin excoriation (>20 mm) received advanced elastomeric skin protectant (3M Cavilon Advanced Skin Protectant) applied once every 3-4 days for 2-4 weeks. Ten patients were included, three were selected for discussion. Adoption of this local clinical care pathway resulted in skin healing and improved patient comfort.

P.169 Tissue plasminogen activator in addition to twist drill drainage as a treatment for chronic subdural hematomas – a descriptive analysis

Background: Current literature provides little consensus on universal guidelines for first-line treatment of chronic subdural hematomas (cSDH). However, administration of local tissue plasminogen activator (tPA) may enhance the traditional method of twist drill drainage (TDD). The study aims to explore the efficacy of TDD with and without tPA, at achieving clinically relevant drainage (200mL) and reducing recurrence of cSDH. Methods: A retrospective review of patients (N=34) with cSDH is presented. Patients who received TDD with tPA (n=17) were identified and matched, based primarily on age and hematoma volume, to a control group (n=17), TDD without tPA. Variables of interest include initial hematoma volume, volume drained, length of stay, and recurrence rates. Descriptive analysis was run. Results: Average age for patients was 74.6 with 76% male. Mean drainage volumes for the tPA cohort was 381.6mL and TDD without tPA cohort was 151.3mL. The addition of tPA resulted in drainage volumes nearly double (1.9x) the clinically relevant amount and had low recurrence rates (12.5%). TDD without tPA failed to result in clinically relevant drainage and had a recurrence rate of 52.9%. Average length of stay differed by two days (9.71 tPA; 7.71 control). Conclusions: TDD with tPA was effective at treating cSDH in our population.

Neonatal Sepsis in a Resource-Limited Setting: Causative Microorganisms and Antimicrobial Susceptibility Profile.

Background Empiric treatment of suspected neonatal sepsis must be based on data on setting-specific causative pathogens and their respective susceptibilities to antimicrobials, as well as universal treatment guidelines. This approach will ensure better therapeutic outcomes and reduce mortality. Objectives The objectives of this study were to determine the bacteriological profile and antibiotic susceptibility pattern of isolated microorganisms responsible for neonatal sepsis in a regional hospital in Ghana. Methods This was a retrospective study that assessed causative microorganisms and antimicrobial susceptibility profiles of neonates suspected of sepsis at the Greater Accra Regional Hospital from January 2018 to December 2019. Blood culture was done using a fully automated BACTEC 9240 blood culture system. Bacteria isolates were identified by Gram staining and conventional biochemical methods. Antimicrobial susceptibility testing was done by Kirby–Bauer's disc diffusion method, and interpretations were carried out according to clinical and laboratory standards. Culture and antibiotic sensitivity reports were obtained and the data subsequently analyzed. Results Of 2514 blood samples collected from neonates suspected of neonatal sepsis, 528 (21.0%) of the samples were found to be culture-positive. The majority of these positive cultures were from male neonates (68.9%). A total of 11 different pathogens were isolated, of which Gram-positive organisms had a preponderance of 72.0% over Gram-negative organisms (28.0%). Staphylococcus epidermidis was the most common pathogen identified, accounting for 60.0% of isolates. The most prevalent Gram-negative bacteria were Klebsiella spp. (13.6%). Most Gram-positive microorganisms showed sensitivity to amikacin, meropenem, vancomycin, and piperacillin/tazobactam. Gram-positive isolates were found to be resistant to ampicillin and penicillin, but moderately susceptible to flucloxacillin. Most Gram-negative isolates were sensitive to meropenem. Conclusion The prevalence of culture-proven sepsis was 21.0%. The most prevalent Gram-negative bacteria were Klebsiella spp. As there is some level of antibiotic resistance observed in the current study, it is necessary for routine microbial analysis of samples and their antibiogram.

Náhle vzniklá percepční nedoslýchavost u dětí: přehled dia­gnostiky, terapie a prognóza

Introduction: Sudden sensorineural hearing loss (SSHL) is an acute condition in children. Universal guidelines for treatment and dia­gnosis are not defined. Use of objective dia­gnostic methods in hearing threshold level verification is necessary. Standardized follow-up care is essential for adequate correction of hearing impairment. Methods and material: This retrospective study analysed 14 patients suffering from SSHL, hospitalized between 2016 and 2019 in a tertiary centre. Age, gender, affected side, hearing threshold level, symptoms, cause and treatment were compared. Hearing loss was classified according to the WHO methodology. The recovery rate was assessed by Siegel’s criteria. Results: All children were treated with an initial dose of 5 mg/kg/day of methylprednisolone intravenously. A complete recovery in our group was achieved in 6 cases (43%). The rate of treatment failure was 75% for the left side and 16.7% for right side SSHL. Patients with the presence of tinnitus have a 54.5% chance of hearing restitution, as compared to 35.3% in patients without tinnitus. The risk of treatment failure for children aged 5–10 years, 10–15 years and 15–18 years is 33%, 83% and 20% respectively. We did not observe any effect on hearing recovery for the other analysed parameters. Conclusions: Better hearing recovery was observed in children with tinnitus, the right affected side and a higher severity of initial hearing loss. At the age of 10–15 years, the chance of hearing recovery was three times lower than in other age groups. Key words sudden sensorineural hearing loss – children – correction of hearing impairment

Comparative Efficacy of Different Oral Doses of Clindamycin in Preventing Post-Operative Sequelae of Lower Third Molar Surgery-A Randomized, Triple-Blind Study.

Background and Objectives. Antibiotic regimen optimization is a major concern in post extraction sequelae management following third molar surgery, mostly owing to the absence of universal guidelines. Hence, this study aimed to determine the effect of antibiotic prophylaxis using three different doses of clindamycin on the prevention of infection and other complications following mandibular third molar disimpaction. The secondary outcome was testing whether clindamycin exhibits activity in acute or chronic models of pain using the visual analog scale of pain and the necessity for post-operative rescue analgesia. The tertiary outcome was to assess clindamycin penetration into the saliva by measuring its concentration using liquid chromatography/electrospray ionization tandem mass spectrometry. Materials and Methods. A randomized, two-center, triple-blind, controlled clinical trial was conducted, in which the patients were randomly allocated to three groups: I, receiving 150 mg clindamycin every 8 h; II, receiving 300 mg clindamycin every 8 h; and III, receiving 600 mg clindamycin every 12 h. Each group continued the therapy for five days. Results. An overall decrease in the risk of infection and other post-operative complications, such as trismus, edema, dysphagia, and lymphadenopathy, was achieved, with the best results in group I. Conclusion. As no statistical association was observed between clindamycin concentration in saliva and degree of post-operative inflammation, clindamycin concentration, or pain intensity, smaller doses of clindamycin administered over shorter time periods is recommended.

Positive impact of the Covid-19 pandemic on dental education.

This letter describes some positive effects of the Covid-19 pandemic on dental education in India. The apex body of dental education, the Dental Council of India (DCI) has formulated some universal guidelines based on those of the US Center for Disease Control and Prevention, about the use of personal protection and following sterilisation protocols adapted for use in dental clinics, hospitals and academic institutions of dental education in India(1). All individual dental clinics, hospitals and academic institutions have to follow stringent and mandatory sterilisation protocols, hence with the Covid-19 outbreak, some unethical practices of the dental profession such as inadequate sterilisation and improper waste management may be reversed (1,2). Emergency dental procedures also have to follow stringent sterilisation guidelines, to avoid aerosol-generating procedures (1). Dental professionals have been utilising teledentistry facilities during the pandemic which focus on emergency relief of dental pain and infection, and elective planning and scheduling of dental treatment (3).

Demystifying the Barriers and Motivators for the Adoption of Base Isolation Systems in New Zealand

A base isolator is a proven system that can significantly reduce any damage to a building in the event of an earthquake. Despite their efficacy, seismic isolators are not widely used in New Zealand, with only about forty systems in use during the 2010 and 2011 Canterbury Earthquakes. This study seeks to investigate why base isolation systems are not frequently used in seismic strengthening projects and buildings in New Zealand. It also focuses on determining ways in which seismic isolators could become more widely used in New Zealand due to increased seismic activity. This study used an exploratory sequential mixed method design, in which qualitative data were collected first through in-depth face-to-face interviews, analysed, and used to construct the quantitative instrument, which was an online questionnaire. Data were obtained from construction professionals such as architects, engineers, site-based construction personnel, and quantity surveyors. The findings of this study indicated the need for an increased awareness of base isolation systems and improved universal guidelines for the design of seismic isolators. The motivators identified include provision of monetary incentives, such as reduced insurance premiums and financial subsidies, to encourage the adoption of seismic isolators. The factors preventing the adoption of base isolation systems in New Zealand were classified as human-related, safety and design-related, and cost-related. The study’s implication is that providing a universal guideline for seismic isolators can enhance designers’ confidence. Likewise, incentives may be provided to property owners to lower the cost of implementing a base isolation system.

The Martial Temple in the Song

ABSTRACT The Martial Temple during China's Song dynasty (960–1279) was the locus of the government's efforts to define the scope of correct martial activity with the entire empire. Correct martial behaviour was defined by the selection of 72 martial exemplars, generals and strategists from history, as well as men who helped found the dynasty. These exemplars were the counterpoint to the Civil Temple that faced it, where Confucius and his 72 close disciples were worshipped. Although the Civil and Martial Temples were sites for worship by the emperor, there is some evidence that there were branch temples around the empire. While the civil exemplars were historically fixed, the martial exemplars were fluid and the subject of regular debate. The martial exemplars, unlike the civil exemplars, were often men from non-elite backgrounds who were far more accessible to the non-elite population of the Song. As such, they were paradigmatic models of non-elite, male service to the state. The Martial Temple was a ritual site that established universal guidelines for legitimate martial practice. Exemplary figures would receive sacrifices not only from the Song state but also quite possibly from subsequent dynastic governments. Some of the chosen exemplars were later absorbed into popular culture through theatre and novels because of that ritual status. Others proceeded in the opposite direction, raised to prominence in literature, and then moved into the Martial Temple.

Insulin Titration Guidelines for Patients With Type 1 Diabetes: It Is About Time!

A proposal that an Insulin Advisory Committee develop insulin titration guidelines 100 years after its discovery. Glucose control metrics remain poor despite significant advances in diabetes technology. A century after the introduction of insulin, health care providers and patients with type 1 diabetes have worldwide access to a variety of insulin delivery devices (IDDs), glucose monitors, bolus calculators (BCs), continuous glucose monitors (CGMs), and automated insulin delivery (AID) systems. However, these advances have not enabled most patients to achieve today's clear A1c and time-in-range goals. Much of this failure arises from the lack of clear insulin titration guidelines for determining appropriate insulin doses. The lack of dosing clarity results in local physicians, clinics, and individual patients managing insulin titrations as they see fit, creating significant inefficiencies for reaching recommended glycemic goals. This review (1) details the widespread problems generated by nonphysiological dose settings in today's BCs, insulin pumps, and AID systems; (2) presents a method to develop and implement optimized total daily doses of insulin to correct the most common problem of hyperglycemia; (3) discusses using large device databases to provide clear insulin titration guidelines that optimize BC settings from an optimized total daily dose (TDD) of insulin for patients with T1D; and (4) recommends the formation of an Insulin Advisory Committee to clarify the steps to take toward universal insulin titration guidelines, optimized BC settings, and a systematic logic for their use in insulin delivery devices.

Asthma–chronic obstructive pulmonary disease overlap syndrome – a brief review

Asthma and chronic obstructive pulmonary disease (COPD) are common disease observed worldwide. The etiologies of these conditions may be different, but their manifestations lead to inflammation and limited airflow. A small subject of population doesn’t meet the criteria of asthma or COPD. As a result, in more recent, years a new clinical entity has gained attraction that encompasses the criteria of both asthma and COPD called Asthma COPD overlap syndrome (ACOS). Thus far, no universal guidelines have been established, therefore, making it problematic for physician to develop a successful treatment strategy for their patients. This review provides a brief description of ACOS including risk factors and treatments. A Medline/PubMED search was performed to find articles with “ACOS” as a heading.

Donor Derived Coccidioides in a Lung Transplant Recipient

<h3>Introduction</h3> There are no universal guidelines on screening donors for coccidioides. We describe a fatal case of coccidioides empyema from a donor previously residing in an endemic region. <h3>Case Report</h3> This is a 72 year old male, status post right single lung transplantation 3 weeks prior for chronic hypersensitivity pneumonitis, who presents to clinic with a productive cough. The donor was a 31 year old male with no medical history from the southern inland region of California. A chest X-ray in clinic demonstrated a right pleural effusion. He underwent thoracentesis and bronchoscopy on post-operative day (POD) 22. Pleural fluid was lymphocytic and exudative with negative cultures, and transbronchial biopsies showed mild acute cellular rejection. He was treated with pulse dose steroids. His symptoms worsened one week later when he was seen in the emergency department. Chest CT showed a large right loculated pleural effusion. The patient was started on broad spectrum antibiotics, and a thoracostomy tube was placed, demonstrating a neutrophil predominant exudate. Repeat chest CT showed the effusion extending through the chest wall, and an additional thoracostomy tube was placed. The patient became more hypoxemic requiring mechanical ventilation and VV-ECMO. Pleural cultures taken two-days prior demonstrated mold and the patient underwent irrigation with amphotericin in the operating room, along with intravenous amphotericin. Ultimately, the patient had multi-organ failure and cardiac arrest. Following his passing, pleural fluid cultures confirmed growth of Coccidioides immitis. <h3>Summary</h3> This case describes a patient with initial negative serologies to coccidioides and a donor from the southern inland region of California, where the incidence of coccidioides is increasing. Transmission of donor-derived coccidioides has been shown to be 43% within 30 days post-transplant, with a 29% mortality. Given the high mortality and treatment availability, screening donors in endemic areas with serologies may prevent post-transplant complications.

Lacticaseibacillus rhamnosus GG Counteracts Rotavirus-Induced Ion Secretion and Enterocyte Damage by Inhibiting Oxidative Stress and Apoptosis Through Specific Effects of Living and Postbiotic Preparations.

BackgroundAdministration of Lacticaseibacillus rhamnosus GG (LGG) to children with gastroenteritis is recommended by universal guidelines. Rotavirus (RV) causes diarrhea through combined cytotoxic and enterotoxic effects. Aim of this study was to evaluate the mechanisms of efficacy of LGG in an in-vitro model of RV diarrhea in its viable form (LGG) and conditioned medium (mLGG).MethodsIon secretion corresponding to the NSP4 enterotoxic effect, was evaluated by short circuit current (Isc) and the cytotoxic effect by transepithelial electrical resistance (TEER) in Ussing chambers, upon exposure to RV in Caco-2 enterocyte monolayers treated or not with living probiotic or its culture supernatant. Mechanisms of enterotoxic and cytotoxic damage were evaluated including oxidative stress measured by reactive oxygen species, apoptosis evaluated by DAPI and nuclear staining, NFkβ immunofluorescence.ResultsRV induced Isc increase and TEER decrease, respectively indicating ion secretion and epithelial damage, the two established pathways of diarrhea. Both probiotic preparations reduced both diarrheal effects, but their potency was different. Live LGG was equally effective on both enterotoxic and cytotoxic effect whereas mLGG was highly effective on ion secretion and showed minimal protective effects on cytoskeleton, apoptosis and NFkβ.ConclusionsLGG counteracts RV-induced diarrhea by inhibiting both cytotoxic and enterotoxic pathogenic mechanisms. Namely, LGG inhibits chloride secretion by specific moieties secreted in the medium with a direct pharmacologic-like action. This is considered a postbiotic effect. Subsequently, live bacteria exert a probiotic effect protecting the enterocyte structure.

Follow-up of primary melanoma patients with high risk of recurrence: recommendations based on evidence and consensus.

In spite of the good prognosis of patients with early-stage melanoma, there is a substantial proportion of them that develop local or distant relapses. With the introduction of targeted and immune therapies for advanced melanoma, including at the adjuvant setting, early detection of recurrent melanoma and/or second primary lesions is crucial to improve clinical outcomes. However, there is a lack of universal guidelines regarding both frequency of surveillance visits and diagnostic imaging and/or laboratory evaluations. In this article, a multidisciplinary expert panel recommends, after careful review of relevant data in the field, a consensus- and experience-based follow-up strategy for melanoma patients, taking into account prognostic factors and biomarkers and the high-risk periods and patterns of recurrence in each (sub) stage of the disease. Apart from the surveillance intensity, healthcare professionals should focus on patients' education to perform regular self-examinations of the skin and palpation of lymph nodes.