Global predictors of tracheostomy-related pressure injury in the COVID-19 era: A study of secondary data.

OBJECTIVES: To determine the incidence and risk factors of tracheostomy-related pressure injuries (TRPI) and examine the COVID-19 pandemic's impact on TRPI incidence. DESIGN: Secondary analysis of Global Tracheostomy Collaborative database and a multi-center hospital system's electronic medical records. SETTING: 27 hospitals, primarily in the United States, United Kingdom, and Australasia. PATIENTS: 6,400 adults and 2,405 pediatric patients hospitalized with tracheostomy between 1 January 2019 and 31 December 2021. MEASUREMENT: TRPI as a binary outcome, reported as odds ratios. RESULTS: TRPI incidence was 4.69 % in adults and 5.65 % in children. For adults, associated risks were female sex (OR: 0.64), severe obesity (OR: 2.62), ICU admission (OR: 2.05), cuffed tracheostomy (OR: 1.49), fenestrated tracheostomy (OR: 15.37), percutaneous insertion (OR: 2.03) and COVID-19 infection (OR: 1.66). For children, associated risks were diabetes mellitus (OR: 4.31) and ICU admission (OR: 2.68). TRPI odds increased rapidly in the first 60 days of stay. Age was positively associated with TRPI in adults (OR: 1.014) and children (OR: 1.060). Black patients had higher TRPI incidence than white patients; no moderating effects of race were found. Hospital cluster effects (adults ICC: 0.227; children ICC: 0.138) indicated unmeasured hospital-level factors played a significant role. CONCLUSIONS: Increasing age and length of stay up to 60 days are TRPI risk factors. Other risks for adults were female sex, severe obesity, cuffed/fenestrated tracheostomy, percutaneous insertion, and COVID-19; for children, diabetes mellitus and FlexTend devices were risks. Admission during the COVID-19 pandemic had contrasting effects for adults and children. Additional research is needed on unmeasured hospital-level factors. IMPLICATIONS FOR CLINICAL PRACTICE: These findings can guide targeted interventions to reduce TRPI incidence and inform tracheostomy care during public health crises. Hospital benchmarking of tracheostomy-related pressure injuries is needed.

PSMA-Targeted Therapy: Advancements in Detection and Treatment Modalities with Dr. Scott T. Tagawa.

Prostate cancer is one of the most challenging malignancies due to its high incidence and prevalence, as it is the most frequently diagnosed non-skin cancer in men. The timely identification of prostate cancer and its metastasis is paramount for ensuring favorable outcomes for patients. Prostate-specific membrane antigen (PSMA) emerges as a promising biomarker for its detection, due to its specificity. This makes it an ideal target for the early identification of a metastatic phenotype. Situated on the membrane of tumor cells, PSMA facilitates the attachment of PSMA-targeting particles, enabling their detection through positron emission tomography (PET) scans with relative ease. Utilizing these imaging agents in conjunction with PET scans enhances the accuracy of prostate cancer tumor detection compared to PET scans alone. The advancement in prostate cancer imaging has paved the way for innovative treatment modalities. Prostate-specific membrane antigen-targeted radionuclide therapies (PSMA-TRT) exploit PSMA imaging agents to target identified prostate cancer malignancies with precise radiation, thereby reducing or eliminating the tumor mass. PSMA-TRT exhibits significant promise in prostate cancer therapy, evident from the notable declines in prostate-specific antigen (PSA) levels post treatment. However, PSMA-TRT carries both beneficial and adverse effects. While it represents a substantial leap forward in tumor cell imaging, PSMA-based antigens, being larger particles than ligands, offer prolonged imaging capabilities. Yet, the long-term effects of PSMA-TRT remain unknown, with the short-term adverse ones including fatigue, nausea, pain flares, and potential radiation exposure to others.

Reimagining Colorectal Cancer Screening: Innovations and Challenges with Dr. Aasma Shaukat.

Colorectal cancer (CRC) currently ranks as the third most common cancer and the second leading cause of cancer-related deaths worldwide, posing a significant global health burden to the population. Recent studies have reported the emergence of a new clinical picture of the disease, with a notable increase in CRC rates in younger populations of <50 years of age. The American Cancer Society (ACS) now recommends CRC screening starting at age 45 for average-risk individuals. Dr. Aasma Shaukat's Keynote Conference highlights the critical need for updated screening strategies, with an emphasis on addressing the suboptimal adherence rates and the effective management of the growing burden of CRC. Lowering the adenoma detection screening age can facilitate early identification of adenomas in younger asymptomatic patients, altering the epidemiologic landscape. However, its implications may not be as profound unless a drastic shift in the age distribution of CRC is observed. Currently, various screening options are available in practice, including stool-based tests like multitarget stool DNA (mtDNA) tests, fecal immunochemical testing (FIT), and imaging-based tests. In addition to existing screening methods, blood-based tests are now emerging as promising tools for early CRC detection. These tests leverage innovative techniques along with AI and machine learning algorithms, aiding in tumor detection at a significantly earlier stage, which was not possible before. Medicare mandates specific criteria for national coverage of blood-based tests, including sensitivity ≥ 74%, specificity ≥ 90%, FDA approval, and inclusion in professional society guidelines. Ongoing clinical trials, such as Freenome, Guardant, and CancerSEEK, offer hope for further advancements in blood-based CRC screening. The development of multicancer early detection tests like GRAIL demonstrates a tremendous potential for detecting various solid tumors and hematologic malignancies. Despite these breakthroughs, the question of accessibility and affordability still stands. The ever-evolving landscape of CRC screening reflects the strength of the scientific field in light of an altered disease epidemiology. Lowering screening age along with the integration of blood-based tests with existing screening methods holds great potential in reducing the CRC-related burden. At the same time, it is increasingly important to address the challenges of adaptation of the healthcare system to this change in the epidemiologic paradigm.

Reviewing the Landscape of Cancer Survivorship: Insights from Dr. Lidia Schapira's Programs and Beyond.

The constantly escalating population of cancer survivors worldwide has prompted a focused exploration of their unique needs and experiences within the context of healthcare medicine. This review initiates its analysis inspired by Dr. Lidia Schapira's insightful keynote conference on the Survivorship 1.0 and Survivorship 2.0 Programs, shedding light on their implementation challenges and setting the stage for a comprehensive analysis of cancer survivorship initiatives. Within the transformed landscape of cancer care, patient-centric strategies embedded in cancer survivorship programs comprising vital elements such as connection, support, and education are presented. While placing cancer recurrence surveillance at the forefront, the review underlines concern regarding the potential oversight of the enduring impact on mental and physical health. Dr. Schapira's insights further extend into the exploration of mental health challenges faced by survivors, promoting an examination of diverse strategies to address these concerns. Furthermore, the discussion continues toward promising areas of research, notably Precision Medicine's role in de-escalating cancer therapies, and advocates for measures such as early cancer awareness and timely referrals to supportive services. Highlighting the significance of education, the role of online resources in enhancing the knowledge of healthcare practitioners and future generations in cancer care is then explored. The paper concludes by presenting some of the most prominent global current survivorship programs, identifying critical knowledge gaps in cancer care and projecting future developments aimed at delivering accurate and holistic care, improving the quality of life for survivors, and enhancing both mental and physical well-being. Drawing upon the insights from Dr. Schapira, this review lays the groundwork for a nuanced exploration of cancer survivorship and its multifaceted implications.

Cholangiocarcinoma Insights: Established Foundations and Cutting-Edge Innovations from Dr. James Cleary's Pioneering Research.

This paper provides insights into the conventional understanding of biliary tract malignancies, with a specific focus on cholangiocarcinoma (CCA). We then delve into the groundbreaking ideas presented by Dr. James Cleary. CCA, originating from biliary tree cells, manifests diverse subtypes contingent upon anatomical localization and differentiation status. These variants exhibit discrete genetic aberrations, yielding disparate clinical phenotypes and therapeutic modalities. Intrahepatic, perihilar, and distal CCAs intricately involve distinct segments of the biliary tree, further categorized as well-differentiated, moderately differentiated, or poorly differentiated adenocarcinomas based on their histological differentiation. Understanding the etiological factors contributing to CCA development assumes paramount importance. Stratifying these factors into two groups, those unrelated to fluke infestations (e.g., viral hepatitis and fatty liver conditions) and those associated with fluke infestations (e.g., chronic liver inflammation), facilitates predictive modeling. The epidemiology of CCA exhibits global variability, with Southeast Asia notably displaying higher incidences attributed primarily to liver fluke infestations. Jaundice resulting from bile duct obstruction constitutes a prevalent clinical manifestation of CCA, alongside symptoms like malaise, weight loss, and abdominal pain. Diagnostic challenges arise due to the symptomatic overlap with other biliary disorders. Employing comprehensive liver function tests and imaging modalities such as computed tomography assumes a pivotal role in ensuring accurate diagnosis and staging. However, the definitive confirmation of CCA necessitates a biopsy. Treatment modalities, predominantly encompassing surgical resection and radiation therapy, hold curative potential, although a considerable subset of patients is deemed unresectable upon exploration. Challenges intensify, particularly in cases classified as cancer of unknown origin, underscoring the imperative for early intervention. Advancements in genomic sequencing have revolutionized precision medicine in CCA. Distinct genomic markers, including fibroblast growth factor receptor 2 (FGFR2) alterations and isocitrate dehydrogenase 1 (IDH1) mutations, have emerged as promising therapeutic targets. FGFR2 alterations, encompassing mutations and rearrangements, play pivotal roles in oncogenesis, with FGFR inhibitors demonstrating promise despite identified resistance mechanisms. Similarly, IDH1 inhibitors face challenges with resistance, despite encouraging early clinical trial results, prompting exploration of novel irreversible inhibitors. Dr. James Cleary's illuminating discourse underscores the significance of diverse FGFR2 alterations and the potential of IDH1 inhibition in reshaping the treatment landscape for CCA. These findings unveil critical avenues for targeted therapeutic interventions, emphasizing the critical need for ongoing research to optimize outcomes in this challenging cancer subtype, incorporating innovative insights from Dr. Cleary.

Innovations in Thoracic Oncology and the Promise of Liquid Biopsies with Dr. Luis Raez.

Thoracic oncology continues to pose a great threat to human health as one of the most common forms of cancer. Liquid biopsies present a transformative approach to treating patients affected by these types of diseases by providing a less invasive genetic overview of the tumor, aiding in both diagnostic and treatment measures. The primary objective of this article is to examine the prospects of liquid biopsies in managing thoracic malignancies and to present barriers to their usage as demonstrated by Dr. Luis Raez. In examining why molecular diagnostics continue to be employed together with more traditional methods, this article presents the next steps in the clinical application of blood-based cancer screening. Future cancer diagnosis and treatment aim to prioritize circulating biomarker analyses based on their potential for the detection and monitoring of thoracic cancers. Liquid biopsies are favored thanks to their reduced invasiveness with respect to traditional treatments. The further study of clinical biomarkers and technological advancements are thus pivotal to enhance the clinical applicability of this method. In conclusion, this blood-based analysis offers a promising route by which the diagnosis, treatments, and outcomes of thoracic cancer can be improved.

Sacituzumab Govitecan in Combination With Pembrolizumab for Patients With Metastatic Urothelial Cancer That Progressed After Platinum-Based Chemotherapy: TROPHY-U-01 Cohort 3.

PURPOSE: Pembrolizumab is standard therapy for patients with metastatic urothelial cancer (mUC) who progress after first-line platinum-based chemotherapy; however, only approximately 21% of patients respond. Sacituzumab govitecan (SG) is a trophoblast cell surface antigen-2-directed antibody-drug conjugate with US Food and Drug Administration-accelerated approval to treat patients with locally advanced or mUC who previously received platinum-based chemotherapy and a checkpoint inhibitor (CPI). Here, we report the primary analysis of TROPHY-U-01 cohort 3. METHODS: TROPHY-U-01 (ClinicalTrials.gov identifier: NCT03547973) is a multicohort, open-label phase II study. Patients were CPI-naïve and had mUC progression after platinum-based chemotherapy in the metastatic setting or ≤12 months in the (neo)adjuvant setting. Patients received 10 mg/kg of SG once on days 1 and 8 and 200 mg of pembrolizumab once on day 1 of 21-day cycles. The primary end point was objective response rate (ORR) per central review. Secondary end points included clinical benefit rate (CBR), duration of response (DOR) and progression-free survival (PFS) per central review, and safety. RESULTS: Cohort 3 included 41 patients (median age 67 years; 83% male; 78% visceral metastases [29% liver]). With a median follow-up of 14.8 months, the ORR was 41% (95% CI, 26.3 to 57.9; 20% complete response rate), CBR was 46% (95% CI, 30.7 to 62.6), median DOR was 11.1 months (95% CI, 4.8 to not estimable [NE]), and median PFS was 5.3 months (95% CI, 3.4 to 10.2). The median overall survival was 12.7 months (range, 10.7-NE). Grade ≥3 treatment-related adverse events occurred in 61% of patients; most common were neutropenia (37%), leukopenia (20%), and diarrhea (20%). CONCLUSION: SG plus pembrolizumab demonstrated a high response rate with an overall manageable toxicity profile in patients with mUC who progressed after platinum-based chemotherapy. No new safety signals were detected. These data support further evaluation of SG plus CPI in mUC.

Intermittent cytomegalovirus infection alters neurobiological metabolism and induces cognitive deficits in mice.

Risk factors contributing to dementia are multifactorial. Accumulating evidence suggests a role for pathogens as risk factors, but data is largely correlative with few causal relationships. Here, we demonstrate that intermittent murine cytomegalovirus (MCMV) infection of mice, alters blood brain barrier (BBB) permeability and metabolic pathways. Increased basal mitochondrial function is observed in brain microvessels cells (BMV) exposed to intermittent MCMV infection and is accompanied by elevated levels of superoxide. Further, mice score lower in cognitive assays compared to age-matched controls who were never administered MCMV. Our data show that repeated systemic infection with MCMV, increases markers of neuroinflammation, alters mitochondrial function, increases markers of oxidative stress and impacts cognition. Together, this suggests that viral burden may be a risk factor for dementia. These observations provide possible mechanistic insights through which pathogens may contribute to the progression or exacerbation of dementia.

The Potential of Lifestyle Medicine: Strategies to Optimize Health and Well-Being in Oncology Care with Dr. Amy Comander.

The field of lifestyle medicine in cancer care and survivorship is undergoing significant transformation, presenting both challenges and opportunities. This collection of insights and reflections by an esteemed speaker aims to address critical facets of this evolving landscape and the intersection of healthcare, lifestyle, and cancer. With a focus on optimizing the health of cancer survivors, the speaker emphasizes the correlation between general population health and strategies for mitigating cancer risk. Evidence-based resources have a key role in their comprehensive insights into lifestyle changes' role in cancer prevention and survivorship. Lifestyle interventions also have a promising role in mitigating the late effects in the pediatric context. Therefore, encouraging the early adoption of healthy practices in childhood cancer survivors emerges as a pivotal strategy. Furthermore, challenges in enhancing education and access to lifestyle medicine are addressed. This highlights the importance of patient-centered communication, motivational interviewing, and personalized guidance in facilitating lifestyle changes with patients. Finally, the role of nutritionists in advising breast cancer patients to consider calorie restriction to lower IGF-1 levels is explored. This collection underscores the multifaceted nature of lifestyle medicine in cancer care, highlighting challenges, opportunities, and the transformative power of passion and curiosity in shaping healthcare careers.

The Evolving Landscape: Exploring the Future of Myelodysplastic Syndrome Treatment with Dr. Rami Komrokji.

This perspective delves into the evolving landscape of Myelodysplastic Syndrome (MDS) treatment. MDS presents a significant clinical challenge, often progressing to acute myeloid leukemia. For low-risk MDS, the emphasis is on personalized care through comprehensive risk assessment, clinical monitoring, and tailored interventions, including promising agents like erythropoiesis-stimulating agents, lenalidomide, and luspatercept, with the anticipation of an expanding therapeutic arsenal and early intervention for improved outcomes. In contrast, high-risk MDS treatment is evolving towards upfront doublet or triplet therapies with a focus on minimal residual disease (MRD) monitoring. A holistic approach integrates various modalities, including stem cell transplant and post-transplant maintenance, all guided by individual patient circumstances. Risk-adapted strategies are crucial for enhancing patient outcomes. Precision medicine for MDS treatment is budding, largely driven by Next Generation Sequencing (NGS). NGS aids in early diagnosis, prognostication, and the targeting of specific mutations, with molecular data increasingly informing treatment responses and allowing for tailored interventions. Clinical trials within homogeneous patient groups with similar molecular profiles are becoming more common, enhancing treatment precision. In conclusion, the future of MDS treatment is moving towards personalized medicine, leveraging advanced technologies like NGS and molecular insights to improve outcomes in the realm of hematological malignancies.

Rapidly developed, optimized, and applied wastewater surveillance system for real-time monitoring of low-incidence, high-impact MPOX outbreak.

Recent MPOX viral resurgences have mobilized public health agencies around the world. Recognizing the significant risk of MPOX outbreaks, large-scale human testing, and immunization campaigns have been initiated by local, national, and global public health authorities. Recently, traditional clinical surveillance campaigns for MPOX have been complemented with wastewater surveillance (WWS), building on the effectiveness of existing wastewater programs that were built to monitor SARS-CoV-2 and recently expanded to include influenza and respiratory syncytial virus surveillance in wastewaters. In the present study, we demonstrate and further support the finding that MPOX viral fragments agglomerate in the wastewater solids fraction. Furthermore, this study demonstrates that the current, most commonly used MPOX assays are equally effective at detecting low titers of MPOX viral signal in wastewaters. Finally, MPOX WWS is shown to be more effective at passively tracking outbreaks and/or resurgences of the disease than clinical testing alone in smaller communities with low human clinical case counts of MPOX.

Development of a CRISPR-Cas12a rapid diagnostic for human cytomegalovirus.

Despite decades of research, human cytomegalovirus (CMV) continues to contribute to significant morbidity and mortality in transplant settings and remains the leading cause of viral congenital infections. Clinical diagnosis of CMV infection and/or reactivation under these settings is completed using real time quantitative polymerase chain reaction (RT-qPCR). This assay performs well but is hampered by poor sensitivity and a lack of standardization among testing facilities. A point-of-care rapid diagnostic to determine CMV viremia could address these issues and improve patient care. In this manuscript, we introduce clustered regularly interspaced short palindromic repeats (CRISPR)-Cas12a technology to design and validate a rapid diagnostic for CMV. This system was tested using CMV spiked human saliva and urine samples. Sensitivity of the assay was ∼10 infectious units (IU)/mL. Specificity of the assay was robust and failed to detect other herpesviruses. Collectively, we have designed and validated a rapid diagnostic for CMV that overcomes limitations of the current standard diagnostic. This assay has the potential to be used as a point-of-care screening tool in transplant and neonatal settings.

Cancer and COVID-19: unravelling the immunological interplay with a review of promising therapies against severe SARS-CoV-2 for cancer patients.

Cancer patients, due to their immunocompromised status, are at an increased risk for severe SARS-CoV-2 infection. Since severe SARS-CoV-2 infection causes multiple organ damage through IL-6-mediated inflammation while stimulating hypoxia, and malignancy promotes hypoxia-induced cellular metabolic alterations leading to cell death, we propose a mechanistic interplay between both conditions that results in an upregulation of IL-6 secretion resulting in enhanced cytokine production and systemic injury. Hypoxia mediated by both conditions results in cell necrosis, dysregulation of oxidative phosphorylation, and mitochondrial dysfunction. This produces free radicals and cytokines that result in systemic inflammatory injury. Hypoxia also catalyzes the breakdown of COX-1 and 2 resulting in bronchoconstriction and pulmonary edema, which further exacerbates tissue hypoxia. Given this disease model, therapeutic options are currently being studied against severe SARS-COV-2. In this study, we review several promising therapies against severe disease supported by clinical trial evidence-including Allocetra, monoclonal antibodies (Tixagevimab-Cilgavimab), peginterferon lambda, Baricitinib, Remdesivir, Sarilumab, Tocilizumab, Anakinra, Bevacizumab, exosomes, and mesenchymal stem cells. Due to the virus's rapid adaptive evolution and diverse symptomatic manifestation, the use of combination therapies offers a promising approach to decrease systemic injury. By investing in such targeted interventions, cases of severe SARS-CoV-2 should decrease along with its associated long-term sequelae and thereby allow cancer patients to resume their treatments.

Implementation of an evidence-based accidental tracheostomy dislodgement bundle in a community hospital critical care unit.

BACKGROUND: Tracheostomy dislodgment can lead to catastrophic neurological injury or death. A fresh tracheostomy amplifies the risk of such events, where an immature tract predisposes to false passage. Unfortunately, few resources exist to prepare healthcare professionals to manage this airway emergency. AIM: To create and implement an accidental tracheostomy dislodgement (ATD) bundle to improve knowledge and comfort when responding to ATD. MATERIALS & METHODS: A multidisciplinary team with expertise in tracheostomy developed a 3-part ATD bundle including (1) Tracheostomy Dislodgement Algorithm, (2) Head of Bed Tracheostomy Communication Tool and (3) Emergency Tracheostomy Kit. The team tested the bundle during the COVID-19 pandemic in a community hospital critical care unit with the engagement of nurses and Respiratory Care Practitioners. Baseline and post-implementation knowledge and comfort levels were measured using Dorton's Tracheotomy Education Self-Assessment Questionnaire, and adherence to protocol was assessed. Reporting follows the revised Standards for Quality Improvement Reporting Excellence (SQUIRE). RESULTS: Twenty-four participants completed pre-test and post-test questionnaires. The median knowledge score on the Likert scale increased from 4.0 (IQR = 1.0) pre-test to 5.0 (IQR = 1.0) post-test. The median comfort level score increased from 38.0 (IQR = 7.0) pre-test to 40.0 (IQR = 5.0) post-test). In patient rooms, adherence was 100% for the Head of Bed Tracheostomy Communication Tool and Emergency Tracheostomy Kit. The adherence rate for using the Dislodgement Algorithm was 55% in ICU and 40% in SCU. DISCUSSION: This study addresses the void of tracheostomy research conducted in local community hospitals. The improvement in knowledge and comfort in managing ATD is reassuring, given the knowledge gap among practitioners demonstrated in prior literature. The ATD bundle assessed in this study represents a streamlined approach for bedside clinicians - definitive management of ATD should adhere to comprehensive multidisciplinary guidelines. CONCLUSIONS: ATD bundle implementation increased knowledge and comfort levels with managing ATD. Further studies must assess whether ATD bundles and other standardised approaches to airway emergencies reduce adverse events. Relevance to Clinical Practice A streamlined intervention bundle employed at the unit level can significantly improve knowledge and comfort in managing ATD, which may reduce morbidity and mortality in critically ill patients with tracheostomy.

Prevention of Tracheostomy-Related Pressure Injury: A Systematic Review and Meta-analysis.

BACKGROUND: In the critical care environment, individuals who undergo tracheostomy are highly susceptible to tracheostomy-related pressure injuries. OBJECTIVE: To evaluate the effectiveness of interventions to reduce tracheostomy-related pressure injury in the critical care setting. METHODS: MEDLINE, Embase, CINAHL, and the Cochrane Library were searched for studies of pediatric or adult patients in intensive care units conducted to evaluate interventions to reduce tracheostomy-related pressure injury. Reviewers independently extracted data on study and patient characteristics, incidence of tracheostomy-related pressure injury, characteristics of the interventions, and outcomes. Study quality was assessed using the Cochrane Collaboration's risk-of-bias criteria. RESULTS: Ten studies (2 randomized clinical trials, 5 quasi-experimental, 3 observational) involving 2023 critically ill adult and pediatric patients met eligibility criteria. The incidence of tracheostomy-related pressure injury was 17.0% before intervention and 3.5% after intervention, a 79% decrease. Pressure injury most commonly involved skin in the peristomal area and under tracheostomy ties and flanges. Interventions to mitigate risk of tracheostomy-related pressure injury included modifications to tracheostomy flange securement with foam collars, hydrophilic dressings, and extended-length tracheostomy tubes. Interventions were often investigated as part of care bundles, and there was limited standardization of interventions between studies. Meta-analysis supported the benefit of hydrophilic dressings under tracheostomy flanges for decreasing tracheostomy-related pressure injury. CONCLUSIONS: Use of hydrophilic dressings and foam collars decreases the incidence of tracheostomy-related pressure injury in critically ill patients. Evidence regarding individual interventions is limited by lack of sensitive measurement tools and by use of bundled interventions. Further research is necessary to delineate optimal interventions for preventing tracheostomy-related pressure injury.

Prevention of Endotracheal Tube-Related Pressure Injury: A Systematic Review and Meta-analysis.

BACKGROUND: Hospital-acquired pressure injuries, including those related to airway devices, are a significant source of morbidity in critically ill patients. OBJECTIVE: To determine the incidence of endotracheal tube-related pressure injuries in critically ill patients and to evaluate the effectiveness of interventions designed to prevent injury. METHODS: MEDLINE, Embase, CINAHL, and the Cochrane Library were searched for studies of pediatric or adult patients in intensive care units that evaluated interventions to reduce endotracheal tube-related pressure injury. Reviewers extracted data on study and patient characteristics, incidence of pressure injury, type and duration of intervention, and outcomes. Risk of bias assessment followed the Cochrane Collaboration's criteria. RESULTS: Twelve studies (5 randomized clinical trials, 3 quasi-experimental, 4 observational) representing 9611 adult and 152 pediatric patients met eligibility criteria. The incidence of pressure injury was 4.2% for orotracheal tubes and 21.1% for nasotracheal tubes. Interventions included anchor devices, serial endotracheal tube assessment or repositioning, and barrier dressings for nasotracheal tubes. Meta-analysis revealed that endotracheal tube stabilization was the most effective individual intervention for preventing pressure injury. Nasal alar barrier dressings decreased the incidence of skin or mucosal injury in patients undergoing nasotracheal intubation, and data on effectiveness of serial assessment and repositioning were inconclusive. CONCLUSIONS: Airway device-related pressure injuries are common in critically ill patients, and patients with nasotracheal tubes are particularly susceptible to iatrogenic harm. Fastening devices and barrier dressings decrease the incidence of injury. Evidence regarding interventions is limited by lack of standardized assessments.

Insulin facilitates corneal wound healing in the diabetic environment through the RTK-PI3K/Akt/mTOR axis in vitro.

Diabetic patients can develop degenerative corneal changes, termed diabetic keratopathy, during the course of their disease. Topical insulin has been shown to reduce corneal wound area and restore sensitivity in diabetic rats, and both the insulin receptor (IR) and insulin-like growth factor 1 receptor (IGF-1R) stimulate cell signaling of the PI3K-Akt pathway. The purpose of this study was to assess a mechanism by which improved wound healing occurs by characterizing expression within the PI3K-Akt pathway in corneal epithelial and stromal cells. In vitro scratch tests were used to evaluate wound healing outcomes under variable glucose conditions in the presence or absence of insulin. Protein expression of intracellular kinases in the PI3K pathway, stromal cell markers, and GLUT-1 was evaluated by immunoblotting.TGF-ß1 expression was evaluated by ELISA. Insulin promoted in vitro wound healing in all cell types. In human corneal epithelial cells, insulin did not induce PI3K-Akt signaling; however, in all other cell types evaluated, insulin increased expression of PI3K-Akt signaling proteins compared to vehicle control. Fibroblasts variably expressed α-SMA under all treatment conditions, with significant increases in α-SMA and TGF-ß1 occurring in a dose-dependent manner with glucose concentration. These results indicate that insulin can promote corneal cellular migration and proliferation by inducing Akt signaling. Exogenous insulin therapy may serve as a novel target of therapeutic intervention for diabetic keratopathy.

Machine Learning-Based Short-Term Mortality Prediction Models for Patients With Cancer Using Electronic Health Record Data: Systematic Review and Critical Appraisal.

BACKGROUND: In the United States, national guidelines suggest that aggressive cancer care should be avoided in the final months of life. However, guideline compliance currently requires clinicians to make judgments based on their experience as to when a patient is nearing the end of their life. Machine learning (ML) algorithms may facilitate improved end-of-life care provision for patients with cancer by identifying patients at risk of short-term mortality. OBJECTIVE: This study aims to summarize the evidence for applying ML in ≤1-year cancer mortality prediction to assist with the transition to end-of-life care for patients with cancer. METHODS: We searched MEDLINE, Embase, Scopus, Web of Science, and IEEE to identify relevant articles. We included studies describing ML algorithms predicting ≤1-year mortality in patients of oncology. We used the prediction model risk of bias assessment tool to assess the quality of the included studies. RESULTS: We included 15 articles involving 110,058 patients in the final synthesis. Of the 15 studies, 12 (80%) had a high or unclear risk of bias. The model performance was good: the area under the receiver operating characteristic curve ranged from 0.72 to 0.92. We identified common issues leading to biased models, including using a single performance metric, incomplete reporting of or inappropriate modeling practice, and small sample size. CONCLUSIONS: We found encouraging signs of ML performance in predicting short-term cancer mortality. Nevertheless, no included ML algorithms are suitable for clinical practice at the current stage because of the high risk of bias and uncertainty regarding real-world performance. Further research is needed to develop ML models using the modern standards of algorithm development and reporting.

Darolutamide and Survival in Metastatic, Hormone-Sensitive Prostate Cancer.

BACKGROUND: Darolutamide is a potent androgen-receptor inhibitor that has been associated with increased overall survival among patients with nonmetastatic, castration-resistant prostate cancer. Whether a combination of darolutamide, androgen-deprivation therapy, and docetaxel would increase survival among patients with metastatic, hormone-sensitive prostate cancer is unknown. METHODS: In this international, phase 3 trial, we randomly assigned patients with metastatic, hormone-sensitive prostate cancer in a 1:1 ratio to receive darolutamide (at a dose of 600 mg [two 300-mg tablets] twice daily) or matching placebo, both in combination with androgen-deprivation therapy and docetaxel. The primary end point was overall survival. RESULTS: The primary analysis involved 1306 patients (651 in the darolutamide group and 655 in the placebo group); 86.1% of the patients had disease that was metastatic at the time of the initial diagnosis. At the data cutoff date for the primary analysis (October 25, 2021), the risk of death was significantly lower, by 32.5%, in the darolutamide group than in the placebo group (hazard ratio 0.68; 95% confidence interval, 0.57 to 0.80; P<0.001). Darolutamide was also associated with consistent benefits with respect to the secondary end points and prespecified subgroups. Adverse events were similar in the two groups, and the incidences of the most common adverse events (occurring in ≥10% of the patients) were highest during the overlapping docetaxel treatment period in both groups. The frequency of grade 3 or 4 adverse events was 66.1% in the darolutamide group and 63.5% in the placebo group; neutropenia was the most common grade 3 or 4 adverse event (in 33.7% and 34.2%, respectively). CONCLUSIONS: In this trial involving patients with metastatic, hormone-sensitive prostate cancer, overall survival was significantly longer with the combination of darolutamide, androgen-deprivation therapy, and docetaxel than with placebo plus androgen-deprivation therapy and docetaxel, and the addition of darolutamide led to improvement in key secondary end points. The frequency of adverse events was similar in the two groups. (Funded by Bayer and Orion Pharma; ARASENS ClinicalTrials.gov number, NCT02799602.).

Tracheostomy care and communication during COVID-19: Global interprofessional perspectives.

OBJECTIVE: Investigate healthcare providers, caregivers, and patient perspectives on tracheostomy care barriers during COVID-19. STUDY DESIGN: Cross-sectional anonymous survey SETTING: Global Tracheostomy Collaborative Learning Community METHODS: A 17-item questionnaire was electronically distributed, assessing demographic and occupational data; challenges in ten domains of tracheostomy care; and perceptions regarding knowledge and preparedness for navigating the COVID-19 pandemic. RESULTS: Respondents (n = 115) were from 20 countries, consisting of patients/caregivers (10.4%) and healthcare professionals (87.0%), including primarily otolaryngologists (20.9%), nurses (24.3%), speech-language pathologists (18.3%), respiratory therapists (11.3%), and other physicians (12.2%). The most common tracheostomy care problem was inability to communicate (33.9%), followed by mucus plugging and wound care. Need for information on how to manage cuffs and initiate speech trials was rated highly by most respondents, along with other technical and knowledge areas. Access to care and disposable supplies were also prominent concerns, reflecting competition between community needs for routine tracheostomy supplies and shortages in intensive care units. Integrated teamwork was reported in 40 to 67% of respondents, depending on geography. Forty percent of respondents reported concern regarding personal protective equipment (PPE), and 70% emphasized proper PPE use. CONCLUSION: While safety concerns, centering on personal protective equipment and pandemic resources are prominent concerns in COVID-19 tracheostomy care, patient-centered concerns must also be prioritized. Communication and speech, adequate supplies, and care standards are critical considerations in tracheostomy. Stakeholders in tracheostomy care can partner to identify creative solutions for delays in restoring communication, supply disruptions, and reduced access to tracheostomy care in both inpatient and community settings.