Proactive Treatment Research Articles

Metabolic-suppressed cancer-associated fibroblasts limit the immune environment and survival in colorectal cancer with liver metastasis.

Background: Colorectal cancer liver metastasis is a major risk factor of poor outcomes, necessitating proactive interventions and treatments. Cancer-associated fibroblasts (CAFs) play essential roles in metastasis, with a focus on metabolic reprogramming. However, knowledge about associations between Cancer-associated fibroblasts metabolic phenotypes and immune cell is limited. This study uses single-cell and bulk transcriptomics data to decode roles of metabolism-related subtype of Cancer-associated fibroblasts and immune cells in liver metastasis, developing a CAF-related prognostic model for colorectal cancer liver metastases. Methods: In this study, Cancer-associated fibroblasts metabolism-related phenotypes were screened using comprehensive datasets from The Cancer Genome Atlas and gene expression omnibus (GEO). Cox regression and Lasso regression were applied to identify prognostic genes related to Cancer-associated fibroblasts, and a model was constructed based on the Cancer-associated fibroblasts subtype gene score. Subsequently, functional, immunological, and clinical analyses were performed. Results: The study demonstrated the metabotropic heterogeneity of Cancer-associated fibroblasts cells. Cancer-associated fibroblasts cells with varying metabolic states were found to exhibit significant differences in communications with different immune cells. Prognostic features based on Cancer-associated fibroblasts signature scores were found to be useful in determining the prognostic status of colorectal cancer patients with liver metastases. High immune activity and an enrichment of tumor-related pathways were observed in samples with high Cancer-associated fibroblasts signature scores. Furthermore, Cancer-associated fibroblasts signature score could be practical in guiding the selection of chemotherapeutic agents with higher sensitivity. Conclusion: Our study identified a prognostic signature linked to metabotropic subtype of Cancer-associated fibroblasts. This signature has promising clinical implications in precision therapy for colorectal cancer liver metastases.

Massive transfusion protocol

Hemorrhage from trauma, surgery, obstetric emergencies, and gastrointestinal bleeds remain a cause of potentially preventable deaths for patients. However, transfusions of large amounts of blood products may lead to complications. The development of Massive Transfusion Protocols (MTP), a proactive treatment protocol to manage profound blood loss, has shown improved outcomes for patients requiring immediate and multiple blood transfusions. These guidelines help to recognize hemorrhagic patients in need of an MTP as well as how to best manage this complex protocol.

Treatment and outcome of IgA nephropathy in children from one single center experience

BackgroundThere is no standard recommendation for IgA nephropathy treatment in children.MethodsThis is a retrospective study. From 2012 to 2020, newly diagnosed primary IgAN followed up for at least 1 year were enrolled. The correlation of MESTC scores and clinical index including proteinuria, gross hematuria and renal dysfunction was analyzed. Treatment and clinical response of 6 month, 1year and 3 year at follow up were also analyzed. Complete renal remission was calculated with Kaplan-Meier analysis.ResultsThe median follow up was 36 months, from 12 months to 87months in 40 IgAN children. Angiotensin-converting enzyme inhibitor (ACEI) was applied to all patients. 30% received ACEI alone; 15% received glucocorticoids; 37.5% received glucocorticoids plus cyclophosphamide, 17.5% received glucocorticoids plus mycophenolate mofetil. Individuals with diffuse mesangial hypercellularity (M1) were more likely to have nephrotic range proteinuria compared to patients with M0 (80% vs. 20%, P < 0.01). Complete renal remission at 6-month, 1-year and 3-year follow up is 50.25%, 70% and 87.5% respectively. Five-year complete renal remission calculated by Kaplan-Meier analysis is 58.4%. Although without significant difference, there is trend of better survival with complete renal remission in group of nephrotic range proteinuria onset. There is no severe adverse effect.ConclusionThis study supports the use of glucocorticoids plus immunosuppressive in addition to ACEI in IgA nephrology pediatric patients with proteinuria. We suggest proactive immunosuppressive treatment in IgA nephropathy in children. This is from a single center in China as may not same results in other population.

Systematic Review of Neovascular Age-Related Macular Degeneration Disease Activity Criteria Use to Shorten, Maintain or Extend Treatment Intervals with Anti-VEGF in Clinical Trials: Implications for Clinical Practice.

Clinical trials in neovascular age-related macular degeneration (nAMD) using anti-vascular endothelial growth factor (ant-VEGF) injections use disease activity (DA) criteria to shorten, maintain or increase the interval between injections. Differences in these DA criteria may contribute to differences in the proportions of patients with macular fluid at key timepoints or achieving extended dosing intervals in these trials. We identified, collated and evaluated DA criteria from pivotal anti-VEGF nAMD trials to understand how differences impact on these studies and real-world visual acuity and extending dosing outcomes. This was a systematic review of literature on Pubmed for randomised clinical trials in nAMD using a proactive treatment regimen. We excluded case reports, review articles and studies on fewer than 50 participants. Twelve clinical trials (LUCAS, VIEW, TREX-AMD, FLUID, TREND, RIVAL, ALTAIR, CANTREAT, ARIES, TREX-Conbercept, HAWK & HARRIER, TENAYA & LUCERNE) investigating anti-VEGF treatment of nAMD were identified according to our search strategy. Different studies utilised a different combination of DA criteria. Specifically, six trials included visual acuity change; four included macular thickness change; one included visual acuity change if associated with macular thickness change; one with qualitative optical coherence tomography (OCT) features; four with qualitative OCT features if also associated with visual acuity change; 10 with macular haemorrhage and five with other fluorescein angiographic features. Different clinical trials use different DA criteria when altering the interval between anti-VEGF injections. This makes it difficult to draw meaningful conclusions about secondary outcomes such as proportion of patients treated at extended dosing intervals or proportions of eyes with persistent subretinal or intraretinal fluid. Standardising DA criteria in clinical trials and preferentially using those easily applied in a real-world setting would lead to results more achievable in real-world settings and for a meaningful comparison of treatment durability.

Outcomes of switching from proactive to reactive treatment after developing advanced central neovascular age-related macular degeneration.

We assessed outcomes of eyes with neovascular age-related macular degeneration (nAMD) that switched from proactive (treat-and-extend) to reactive (pro re nata) treatment regimen after developing macular atrophy (MA) or submacular fibrosis (SMFi). Data were collected from a retrospective analysis of a prospectively designed, multinational registry of "real-world" nAMD treatment outcomes. Eyes without MA or SMFi when starting treatment with a vascular endothelial growth factor inhibitor regimen that subsequently developed MA or SMFi were included. Macular atrophy developed in 821 and SMFi in 1166 eyes. Seven percent of eyes that developed MA, and 9% of those that developed SMFi, were switched to reactive treatment. Vision was stable at 12 months for all eyes with MA and inactive SMFi eyes. Active SMFi eyes that switched to reactive treatment had significant vision loss. No eyes that continued proactive treatment developed ≥15 letter loss, but 8% of all eyes that switched to a reactive regimen, and 15% of active SMFi eyes did. Eyes that switch from proactive to reactive treatment after developing MA and inactive SMFi, can have stable visual outcomes. Physicians should be aware of the risk of a significant loss of vision in eyes with active SMFi that switch to reactive treatment.

The evidence bases of etiopathophysiology and preventive clinical management of nausea and vomiting in pregnancy

Nausea and vomiting, or early toxicosis, is a common disorder during pregnancy, affecting up to 80% of pregnant women. The severe form is known as excessive vomiting of pregnancy – hyperemesis gravidarum (HG) and is a debilitating and potentially life-threatening illness during pregnancy which is characterized by persistent nausea and/or vomiting, weight loss, malnutrition and dehydration, increases the risk of adverse maternal and perinatal outcomes.Without the methodical intervention of experienced clinicians, life-threatening complications can develop. Effective prevention and treatment strategies for HG require an understanding of both pathophysiological and psychosocial factors, awareness of potential risks and complications, and proactive assessment and treatment methods using innovative clinical tools. HG is characterized by dehydration, electrolyte and metabolic imbalance, as well as nutritional deficiency, which can lead to hospitalization. The severity of nausea and vomiting during pregnancy can be assessed using the Unique Gestational Vomiting Qualification (scale PUQE-24), which has been shown to be a relatively accurate assessment of the patient’s lifestyle, including hours of sleep.For high-quality differential diagnosis, a focused anamnesis collection and examination are necessary, since the diagnosis of this condition is mainly determined clinically. Laboratory tests are useful tools for evaluating complications such as electrolyte or metabolic imbalances or kidney damage. In addition, they help to determine the etiology in refractory cases.Hypotheses that contribute to the understanding of the pathogenesis of HG have been based on associations that are causal, sequential, or coincidental. Much efforts are needed to precisely establish these relationships in well-designed studies. HG is the most common indication for hospitalization in the first half of pregnancy. Numerous nutrient deficiencies have been identified, such as thiamine deficiency, which can lead to Wernicke’s encephalopathy, vitamin K deficiency, and severe hypokalemia.It is noteworthy that, in addition to the above-mentioned physical complications, HG is also associated with psychological adverse consequences. Although it has been associated with serious complications, little is known about its prognostic factors.The purpose of this systematic review was to find and critically evaluate studies that determined the priority areas of clinical management of vomiting in pregnant women, based on the differentiation and pathophysiological component, the analysis of the safety profile of non-pharmacological agents to prevent the development of the above-mentioned gestational pathology, and the clarification of an effective strategy of interprofessional teams to improve care coordination and outcomes in pregnant women with nausea and vomiting.A systematic data search was carried out in the databases MEDLINE, ISI Web of Science, PubMed, Scopus, Google Scholar, Cochrane Database of Systematic Reviews and Database of Abstracts of Reviews of Effects and publications in professional publications of Ukraine for 2010–2023.The main result was the prediction of the occurrence of vomiting in pregnant women and HG, the effectiveness of preventive intervention, the reduction or cessation of nausea/vomiting; the number of episodes of vomiting; duration of hospitalization. Secondary outcomes included other parameters of preventive strategy effectiveness, adverse maternal/fetal/neonatal outcomes, quality of life measures, and economic costs. Preventive measures: ginger, acupressure/acupuncture, diet, hypnotherapy. The economic evaluation of prevention strategies also took into account perinatal outcomes. Therapeutic strategies, primarily infusion therapy, will be reviewed and analyzed by us in the following review.The results of evidence-based medicine presented in the reviews can be used in the creation of a clinical guideline, protocol, consensus or clinical recommendations regarding the clinical management of nausea, vomiting of pregnancy and HG.

Efficacy of algaecides for the proactive treatment of overwintering cyanobacteria

Once established within a water resource, harmful algal blooms (HABs) can occur seasonally with an intense and rapid onset, giving water resource managers limited time to respond to lessen risks. An attractive strategy to decrease human, ecological, and economic risks from HABs is to implement proactive algaecide treatments applied to overwintering cyanobacteria (i.e., akinetes and quiescent vegetative cells) in sediments prior to the formation of a HAB; however, this approach is novel and very limited efficacy data exist. Therefore, the specific objectives of this research were to 1) evaluate copper- and peroxide-based algaecides, applied as single and repeat treatments at the bench scale, to identify effective proactive treatments, and 2) compare correlations between cell density and other response measurements (i.e., in vivo chlorophyll a and phycocyanin concentrations and percent benthic coverage), to identify informative metrics to assess overwintering cyanobacteria responses. Twelve treatment scenarios using copper- and peroxide-based algaecides were applied to sediments containing overwintering cyanobacteria prior to a 14 d incubation under favorable growth conditions. Responses of cyanobacteria in the planktonic (i.e., cell density, in vivo chlorophyll a and phycocyanin concentrations) and benthic (percent coverage) phases after a 14 d incubation were evaluated in treatments and controls. The HAB-forming cyanobacteria present after a 14 d incubation were: Aphanizomenon, Dolichospermum, Microcystis, Nostoc, and Planktonthrix. Successive treatments of copper sulfate (CuSulfate) followed by sodium carbonate peroxyhydrate (PeroxiSolid) (second algaecide applied after 24 h) as well as repeat applications of a single algaecide, PeroxiSolid (second treatment applied after 24 h) resulted in statistically significant (p ≤ 0.05; α = 0.05) declines in cell density relative to untreated controls. Planktonic cyanobacteria responses measured in terms of phycocyanin concentrations were strongly correlated with cyanobacteria density measurements (Pearson’s correlation coefficient (r) = 0.89). Chlorophyll a concentrations and percent benthic coverage did not correlate with planktonic cyanobacteria density measurements (r = 0.37 and −0.49, respectively) and therefore, were unreliable metrics for cyanobacterial responses in this study. These data provide initial evidence of the efficacy of algaecides for treating overwintering cells in sediments and contribute to our overarching hypothesis that proactive treatments may delay the onset and intensity of HABs in impacted waterbodies.

Vitamin D Deficiency in Chronic Childhood Disorders: Importance of Screening and Prevention.

Vitamin D plays a vital role in regulating calcium and phosphate metabolism and maintaining bone health. A state of prolonged or profound vitamin D deficiency (VDD) can result in rickets in children and osteomalacia in children and adults. Recent studies have demonstrated the pleiotropic action of vitamin D and identified its effects on multiple biological processes in addition to bone health. VDD is more prevalent in chronic childhood conditions such as long-standing systemic illnesses affecting the renal, liver, gastrointestinal, skin, neurologic and musculoskeletal systems. VDD superimposed on the underlying disease process and treatments that can adversely affect bone turnover can all add to the disease burden in these groups of children. The current review outlines the causes and mechanisms underlying poor bone health in certain groups of children and young people with chronic diseases with an emphasis on the proactive screening and treatment of VDD.

Decision-making and challenges within the evolving treatment algorithm in spinal muscular atrophy: a clinical perspective

ABSTRACT Introduction The clinical application of disease modifying therapies has dramatically changed the paradigm of the management of people with spinal muscular atrophy (SMA), from sole reliance on symptomatic care directed toward the downstream consequences of muscle weakness, to proactive intervention and even preventative care. Areas covered In this perspective, the authors evaluate the contemporary therapeutic landscape of SMA and discuss the evolution of novel phenotypes and the treatment algorithm, including the key factors that define individual treatment choice and treatment response. The benefits achieved by early diagnosis and treatment through newborn screening are highlighted, alongside an appraisal of emerging prognostic methods and classification frameworks to inform clinicians, patients, and families about disease course, manage expectations, and improve care planning. A future perspective of unmet needs and challenges is provided, emphasizing the key role of research. Expert opinion SMN-augmenting therapies have improved health outcomes for people with SMA and powered the practice of personalized medicine. Within this new proactive diagnostic and treatment paradigm, new phenotypes and different disease trajectories are emerging. Ongoing collaborative research efforts to understand the biology of SMA and define optimal response are critical to refining future approaches.

Optimización del manejo de la degeneración macular asociada a la edad neovascular en España: evolución hacia modelos proactivos de tratamiento

Introduction and objectiveHealthcare resources optimization is crucial to assume the growing demand of neovascular age-related macular degeneration (nAMD). This work provides guidelines and support so that each hospital can lead its change management. MethodsThe OPTIMUS project (n=10 hospitals) was based on face-to-face interviews with the key staff of the ophthalmology services, and alignment with the main responsible for each centre (nominal group) to identify potential needs for improving nAMD. The OPTIMUS nominal group was expanded to 12 centres (eVOLUTION). Through different remote work sessions, different guides and tools were defined and developed to implement proactive treatment strategies, one-step treatment administration and potential for remote visits (eConsult) in nAMD. ResultsThe information collected from the OPTIMUS interviews and working groups (n=10 centres) defined roadmaps to promote the development of protocols and proactive treatment strategies, including healthcare workload optimization and one-stop treatment administration in nAMD. With eVOLUTION, processes and tools were developed to promote eConsult: (i) healthcare burden calculator; (ii) definition of potential patients for telematic management; (iii) definition of nAMD management archetypes; (iv) definition of processes for implementation of eConsult by archetype; and (v) key performance indicators for changing evaluation. ConclusionsManaging change is an internal task that requires an adequate diagnosis of processes and feasible implementation roadmaps. OPTIMUS and eVOLUTION provide the basic tools for an autonomous advance of hospitals in the optimization of AMD management, with the available resources.

Comparison of proactive and conventional treatment of anastomotic leakage in rectal cancer surgery: a multicentre retrospective cohort series

PurposeComparative studies on efficacy of treatment strategies for anastomotic leakage (AL) after low anterior resection (LAR) are almost non-existent. This study aimed to compare different proactive and conservative treatment approaches for AL after LAR.MethodsThis retrospective cohort study included all patients with AL after LAR in three university hospitals. Different treatment approaches were compared, including a pairwise comparison of conventional treatment and endoscopic vacuum-assisted surgical closure (EVASC). Primary outcomes were healed and functional anastomosis rates at end of follow-up.ResultsOverall, 103 patients were included, of which 59 underwent conventional treatment and 23 EVASC. Median number of reinterventions was 1 after conventional treatment, compared to 7 after EVASC (p < 0.01). Median follow-up was 39 and 25 months, respectively. Healed anastomosis rate was 61% after conventional treatment, compared to 78% after EVASC (p = 0.139). Functional anastomosis rate was higher after EVASC, compared to conventional treatment (78% vs. 54%, p = 0.045). Early initiation of EVASC in the first week after primary surgery resulted in better functional anastomosis rate compared to later initiation (100% vs. 55%, p = 0.008).ConclusionProactive treatment of AL consisting of EVASC resulted in improved healed and functional anastomosis rates for AL after LAR for rectal cancer, compared to conventional treatment. If EVASC was initiated within the first week after index surgery, a 100% functional anastomosis rate was achievable.

Alternative clinical approaches to the treatment of pruritus related with canine atopic dermatitis

Canine atopic dermatitis (CAD) is a genetically inheritable, inflammatory and pruritic skin disease with characteristic clinical features, most commonly associated with IgE antibodies to environmental allergens. Itching is the most prominent clinical finding. Depending on the allergens involved, seasonal or non-seasonal pruritus may occur. &#x0D; In the first active phase of pruritus treatment, which consists of two stages, acute exacerbations should be controlled by drugs with active ingredients such as corticosteroids, oclacitinib, lokivetmab, etc. In the proactive pruritus treatment, it is aimed to prevent exacerbations and prolong the pruritus-free period with maintenance treatment. For this purpose, in addition to active phase of the therapy, different treatment options such as cyclosporine, tacrolimus, antihistamines, essential fatty acids, Palmitoylethanolamide (PEA), topical drugs and shampoos can be used to repair the skin barrier.&#x0D; Due to the side effects and costs of the drugs used in the treatment of pruritus in atopic dermatitis, researches on alternative treatment methods are still continuing. Applications such as mesenchymal stem cell therapy, recombinant canine gamma-interferon, luteolin, vitamin D, vitamin E, lactoferricin/verbascoside, mastinib, cannabidiol (CBD), probiotics and vaccination against IL-31 are the alternative treatment options for atopic dermatitis in dogs. However, more studies are needed before their inclusion in our routine clinical practices and added to the guidelines. In this review, it is aimed to provide information about new treatments used for pruritus in CAD and to encourage their use in routine veterinary clinical practice.

SPINAL MUSCULAR ATROPHY CLINICAL FEATURES, CLASSIFICATION, NATURAL HISTORY, GENETICS, DIAGNOSIS, COMPLICATIONS AND TREATMENT OF THE DISEASE

Introduction: Spinal muscular atrophy (SMA) is a complex neuromuscular disorder, it is the most usual autosomal recessively inherited lethal neuromuscular disease in pediatrics, it presents a defective alteration in the survival motor neuron 1 (SMN1) gene. Spinal muscular atrophy clinically shows progressive weakness of skeletal and respiratory muscles. In recent years, drugs with encouraging results from phase II and III clinical trials have been presented. Objective: to detail current information related to spinal muscular atrophy, clinical features, classification, natural history, genetics, diagnosis, complications and treatment of the disease. Methodology: a total of 40 articles were analyzed in this review, including review and original articles, as well as clinical cases, of which 31 bibliographies were used because the other articles were not relevant to this study. The sources of information were PubMed, Google Scholar and Cochrane; the terms used to search for information in Spanish, Portuguese and English were: spinal muscular atrophy, Spinal Muscular Atrophy, spinal muscular atrophy and spinal muscular atrophy. Results: About 95 % of the occurrences of spinal muscular atrophy are generated by homozygous deletions. Individuals with 5q mutation make up 95% of cases of spinal muscular atrophy and the remaining 5% are generated by mutations in 5q1-5. Targeted treatments may prevent or delay the progression of some symptoms of spinal muscular atrophy. Conclusions: Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease characterized by muscle atrophy and weakness resulting from irreversible loss and progressive degeneration of the brainstem nuclei and anterior horn cells in the spinal cord (lower motor neurons). Clinically it presents with symmetrical proximal limb weakness that also impacts the axial muscles, intercostal and bulbar musculature and is progressive, and the classification protocol is important in genetics, as well as providing prognostic and clinical information. The natural history of the disease is variable and complicated. It is made by demonstrating a history of proximal muscle weakness, motor difficulties or regression, diminished or absent deep tendon reflexes. Among the most frequent complications in unsupported individuals are those previously mentioned such as poor weight gain with growth retardation, scoliosis, restrictive lung disease, joint contractures and sleep difficulties. In terms of treatment, several different compounds have been investigated in recent years, focused on increasing muscle strength and function. Proactive supportive treatment involving a multidisciplinary team is paramount to decrease the severity of symptoms. KEY WORDS: muscle atrophy, spine, spinal, spinal cord, motor neuron.

Digital technology for early identification of exacerbations in people with cystic fibrosis.

Cystic fibrosis (CF) is a life-limiting genetic condition affecting various organ systems including the gastrointestinal tract, endocrine system and especially the respiratory tract. Pulmonary exacerbations in CF result in increased symptoms, an acceleration in the rate of lung decline and an increased need for treatment. Early detection of infections or clinical worsening provides an opportunity for proactive treatment that may affect clinical outcomes. To evaluate whether digital technology can effectively predict pulmonary exacerbations to allow earlier intervention and improved health outcomes without increasing the burden of treatment in people with CF. We used standard, extensive Cochrane search methods. We searched the Cochrane Cystic Fibrosis Trials Register and the reference lists of relevant articles and reviews on 13 October 2022. We searched Embase and the clinical trial registries on 3 January 2023. We included randomised controlled trials (RCTs) or quasi-RCTs in people with CF looking at whether digital technology can effectively predict pulmonary exacerbations to allow earlier intervention and improved health outcomes without increasing the burden of treatment. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were 1. pulmonary exacerbations and 2. quality of life (QoL). Our secondary outcomes were 3. lung function, 4. hospitalisations, 5. intravenous (IV) antibiotics, 6. microbiology, 7. cost-effectiveness and 8. We used GRADE to assess certainty of evidence. We included three studies (415 participants) in people with CF aged 15 to 41 years over a 12-month period. One was a multicentre RCT, whilst two were single-centre RCTs. The three studies were mostly similar in their risk of bias, having low or unclear risk of selection bias but a high risk of detection bias, due to the unblinded design of these studies. The studies used a variety of digital technologies to monitor symptoms such as a digital symptom diary either with or without home spirometry monitoring. As the trials only included adults and older children, we are not certain that the results would apply to younger children. One of our primary outcomes was to assess time to detection of pulmonary exacerbation and number of pulmonary exacerbations identified between the intervention and routine care groups. We were largely unable to pool results in a meta-analysis due to the variety of methodologies and ways of reporting data. Two studies noted a shorter time to detection of exacerbations in the intervention group and one of these also reported that the intervention group had a shorter time to first exacerbation (hazard ratio for time to first exacerbation 1.45, 95% confidence interval (CI) 1.09 to 1.93), whilst a further study reported a shorter time to detection of exacerbations in the intervention group requiring oral or IV antibiotics compared to the control group (median: 70 (interquartile range (IQR) 123) days with intervention versus 141 (IQR 140) days with control; P = 0.02). However, all three studies were concordant in finding no probable effect on spirometry in the intervention groups when compared with their routine care groups over a 12-month period. We found that there is probably no difference between groups with regard to QoL scores across most domains except for Weight and Body Image, which favoured the usual care group. There is also probably no difference in the number of days of additional IV antibiotics needed or newly detected pathogens. No studies reported serious adverse events directly linked to the intervention and one study reported their smartphone application was generally well received. Pulmonary exacerbations are universally accepted to be detrimental to progression of CF-related lung disease, therefore, it is intuitive that early detection and intervention would help to improve outcomes. Digital technology provides an opportunity to detect physiological and symptomatic changes to identify exacerbations early. Our review found that digital technologies based on recording physiological change (spirometry) and symptoms probably allow earlier identification of exacerbations as a group. However, this may not reduce the number of exacerbations warranting IV antibiotics and there is probably no effect on lung function. This may be partly due to inconsistent definitions of pulmonary exacerbations and discrepancy in the management strategies for pulmonary exacerbations. Overall, the intervention may make little or no difference to QoL scores. The adherence to and uptake of digital technologies, especially those which include physiological measurements, are not well sustained and the costs of these need to be balanced against the clinical efficacy.

The promotion of sleep wellness: Resilience as a protective factor.

To evaluate the association between resilience, sleep quality, and health. This cross-sectional study included 190 patients (Mean age = 51, SD = 15.57) recruited from the Johns Hopkins Center for Sleep and Wellness. Patients completed a modified version of the brief resilience scale (BRS) to assess characteristics of resilience and questions to assess aspects of mental health, physical health, sleep quality, and daytime functioning. Participants' average score on the BRS was 4.67 (SD = 1.32, range = 1.17-7), reflecting a high level of resilience. There was a significant gender difference in resilience levels for men (Mean = 5.04, SD = 1.14) and women (Mean = 4.30, SD = 1.38), such that men reported significantly higher levels of resilience compared to women (t (188) = 4.02, p < 0.001) [lower levels of resilience were significantly associated with higher levels of (current) fatigue and tiredness after adjusting for demographic, physical, and mental covariates. In those reporting between one and three mental health symptoms, high levels of resilience minimized the negative influence that these symptoms had on sleep quality. This minimizing effect was no longer evident in those experiencing >3 mental health symptoms, who also reported significantly higher symptoms of fatigue despite their high resilience scores. This study emphasizes how resilience may affect the relationship between mental health and sleep quality in sleep patients. Resilience may further our understanding of the inter-relationships between sleep and the manifestation of physical health symptoms, a relationship that will likely heighten in relevance during personal and global crisis. An awareness of this interaction could be used as a proactive prevention and treatment strategy. In other words, incorporating methods to evaluate resilience in patients with mental illnesses regularly can be useful for predicting the potential manifestation and severity of sleep disturbance. Therefore, strategies that focus on promoting resilience could improve health and wellness.

Saccharomyces cerevisiae surface display of endolysin LysKB317 for control of bacterial contamination in corn ethanol fermentations.

Control of bacterial contamination in bioethanol fermentation facilities has traditionally relied on chemical-based products such as hop acids and use of antibiotics. Recent emphasis on antibiotic stewardship has prompted new research into the development of alternative approaches to microbial remediation strategies. We recently described a recombinant peptidoglycan hydrolase, endolysin LysKB317, which inhibited Limosilactobacillus fermentum strains in corn mash fermentation. Here, Saccharomyces cerevisiae EBY100 was used to anchor recombinant LysKB317 using cell surface display with the a-agglutinin proteins Aga1p-Aga2p. Immunostaining and confocal fluorescence were used for localization of the extracellular interface of the cells. Yeast surface-expressed endolysin demonstrated an 83.8% decrease in bacterial cell counts compared to a 9.5% decrease in control yeast. Recombinant S. cerevisiae expressing LysKB317 used for small-scale corn mash fermentation, when infected with L. fermentum, could proactively control bacterial infection for 72h with at least 1-log fold reduction. Analysis of fermentation products showed improved ethanol concentrations from 3.4% to at least 5.9% compared to the infection-only control and reduced levels of lactic and acetic acid from 34.7mM to 13.8mM and 25.5mM to 18.1mM, respectively. In an optimized yeast surface display system, proactive treatment of bacterial contaminants by endolysin LysKB317 can improve fermentation efficiency in the presence of L. fermentum contamination.

Spectrum of Liver: GI Disorders in Pregnancy.

Pregnant women are affected by gastrointestinal and liver disorders. These may or may not be related to pregnancy. Unrelated conditions are pre-existent or coincidental during pregnancy. Pregnancy may promote symptoms/alter course of new or pre-existing disease resulting in complications only during pregnancy. This in turn can have adverse effect on clinical course affecting mother and fetus. The management remains same but its effect on mother and fetus needs to be kept in mind with pro-active treatment. Severe liver diseases though rare during pregnancy can occasionally be life threatening. Pregnancy after bariatric surgery/liver transplant is possible but with thorough counseling and needs multidisciplinary approach. Endoscopy for GI problems, if required can be carried out by gastroenterologist with special attention. Hence, this article, for quick reference to tackle GI and liver disorders in pregnancy.

Intestinal Permeability Targeted Rectal Enema Nutraceutical Intervention in Dogs with Cutaneous Adverse Food Reactions: Gut-Brain-Skin Axis Directed Pro-active Treatment

Intestinal Permeability Targeted Rectal Enema Nutraceutical Intervention in Dogs with Cutaneous Adverse Food Reactions: Gut-Brain-Skin Axis Directed Pro-active Treatment

Impact of additional genetic abnormalities at diagnosis of chronic myeloid leukemia for first-line imatinib-treated patients receiving proactive treatment intervention.

The BCR::ABL1 gene fusion initiates chronic myeloid leukemia (CML); however, evidence has accumulated from studies of highly selected cohorts that variants in other cancer-related genes are associated with treatment failure. Nevertheless, the true incidence and impact of additional genetic abnormalities (AGA) at diagnosis of chronic phase (CP)-CML is unknown. We sought to determine whether AGA at diagnosis in a consecutive imatinib-treated cohort of 210 patients enrolled in the TIDEL-II trial influenced outcome despite a highly proactive treatment intervention strategy. Survival outcomes including overall survival, progression-free survival, failure-free survival, and BCR::ABL1 kinase domain mutation acquisition were evaluated. Molecular outcomes were measured at a central laboratory and included major molecular response (MMR, BCR::ABL1 ≤0.1%IS), MR4 (BCR::ABL1 ≤0.01%IS), and MR4.5 (BCR::ABL1 ≤0.0032%IS). AGA included variants in known cancer genes and novel rearrangements involving the formation of the Philadelphia chromosome. Clinical outcomes and molecular response were assessed based on the patient's genetic profile and other baseline factors. AGA were identified in 31% of patients. Potentially pathogenic variants in cancer-related genes were detected in 16% of patients at diagnosis (including gene fusions and deletions) and structural rearrangements involving the Philadelphia chromosome (Ph-associated rearrangements) were detected in 18%. Multivariable analysis demonstrated that the combined genetic abnormalities plus the EUTOS long-term survival clinical risk score were independent predictors of lower molecular response rates and higher treatment failure. Despite a highly proactive treatment intervention strategy, first-line imatinib-treated patients with AGA had poorer response rates. These data provide evidence for the incorporation of genomically-based risk assessment for CML.

Enhanced early skin treatment for atopic dermatitis in infants reduces food allergy

Early-onset atopic dermatitis is a strong risk factor for food allergy, suggesting that early effective treatment may prevent transcutaneous sensitization. This study tested whether enhanced treatment of atopic dermatitis to clinically affected and unaffected skin is more effective in preventing hen's egg allergy than reactive treatment to clinically affected skin only. This was a multicenter, parallel-group, open-label, assessor-blind, randomized controlled trial (PACI [Prevention of Allergy via Cutaneous Intervention] study). This study enrolled infants 7-13 weeks old with atopic dermatitis and randomly assigned infants in a 1:1 ratio to enhanced early skin treatment or conventional reactive treatment using topical corticosteroids (TCSs). The primary outcome was the proportion of immediate hen's egg allergy confirmed by oral food challenge at 28 weeks of age. This study enrolled 650 infants and analyzed 640 infants (enhanced [n= 318] or conventional [n= 322] treatment). Enhanced treatment significantly reduced hen's egg allergy compared with the conventional treatment (31.4% vs 41.9%, P= .0028; risk difference: -10.5%, upper bound of a 1-sided CI: -3.0%), while it lowered body weight (mean difference: -422 g, 95% CI: -553 to -292 g) and height (mean difference: -0.8 cm, 95% CI: -1.22 to -0.33 cm) at 28 weeks of age. This study highlighted the potential of well-controlled atopic dermatitis management as a component of a hen's egg allergy prevention strategy. The enhanced treatment protocol of this trial should be modified before it can be considered as an approach to prevent hen's egg allergy in daily practice to avoid the adverse effects of TCSs. After remission induction by TCSs, maintenance therapy with lower potency TCSs or other topical therapies might be considered as alternative proactive treatments to overcome the safety concerns of TCSs.