Use of patient-derived explants as a preclinical model for precision medicine in colorectal cancer: A scoping review.

PURPOSE: Whilst the treatment paradigm for colorectal cancer has evolved significantly over time, there is still a lack of reliable biomarkers of treatment response. Treatment decisions are based on high-risk features such as advanced TNM stage and histology. The role of the tumour microenvironment, which can influence tumour progression and treatment response, has generated considerable interest. Patient-derived explant cultures allow preservation of native tissue architecture and tumour microenvironment. The aim of the scoping review is to evaluate the utility of patient-derived explant cultures as a preclinical model in colorectal cancer. METHODS: A search was conducted using Ovid MEDLINE, EMBASE, Web of Science, and Cochrane databases from start of database records to September 1, 2022. We included all peer-reviewed human studies in English language which used patient-derived explants as a preclinical model in primary colorectal cancer. Eligible studies were grouped into the following categories: assessing model feasibility; exploring tumour microenvironment; assessing ex vivo drug responses; discovering and validating biomarkers. RESULTS: A total of 60 studies were eligible. Fourteen studies demonstrated feasibility of using patient-derived explants as a preclinical model. Ten studies explored the tumour microenvironment. Thirty-eight studies assessed ex vivo drug responses of chemotherapy agents and targeted therapies. Twenty-four studies identified potential biomarkers of treatment response. CONCLUSIONS: Given the preservation of tumour microenvironment and tumour heterogeneity, patient-derived explants has the potential to identify reliable biomarkers, treatment resistance mechanisms, and novel therapeutic agents. Further validation studies are required to characterise, refine and standardise this preclinical model before it can become a part of precision medicine in colorectal cancer.

The Suicidal Patient: Evaluation and Management.

Suicide rates in the United States increased from 20% to 30% between 2005 and 2015, and family physicians need evidence-based resources to address this growing clinical concern. Asking high-risk patients (e.g., patients with previous suicide attempts, substance misuse, low social support) about suicidal intent leads to better outcomes and does not increase the risk of suicide. There is insufficient evidence to support routine screening. Important elements of the patient history include the intent, plan, and means; availability of social support; previous attempts; and the presence of comorbid psychiatric illness or substance misuse. After intent has been established, inpatient and outpatient management should include ensuring patient safety and medical stabilization, activating support networks, and initiating therapy for psychiatric diseases. Care plans for patients with chronic suicidal ideation include these same steps and referral for specialty care. In the event of a completed suicide, physicians should provide support for family members who may be experiencing grief complicated by guilt, while also activating support networks and risk management systems.

Impact of an Electronic Pain and Opioid Risk Assessment Program: Are There Improvements in Patient Encounters and Clinic Notes?

OBJECTIVE: A comprehensive electronic self-report assessment, called PainCAS® (Clinical Assessment System), was developed and implemented in three clinics. PainCAS captures demographic information, pain assessment, quality-of-life variables, and contains validated, electronic versions of screeners for risk of aberrant opioid-related behaviors (the SOAPP and COMM). This investigation sought to determine the impact of PainCAS on documentation of pain and opioid risk evaluations. Exploratory hypotheses examined changes in the content of the patient-provider interaction and any impact on outcome. METHODS: In study 1, chart reviews were conducted between pain patients who completed the electronic program (N = 89) and controls who represented standard of care (N = 120). In study 2, two groups of chronic pain patients (treatment-as-usual Control condition = 75, PainCAS Experimental condition = 72) were interviewed after completing their index clinic visit and completed mailed questionnaires 3 months later. RESULTS: Results revealed significantly more key, pain-relevant chart elements documented in charts of patients who completed the PainCAS than those using a traditional paper questionnaire (Study 1; <0.001). In Study 2, the Experimental group reported more discussion about legal issues, substance use history, and medication safety compared with the Control group (p < 0.05). Satisfaction questionnaire responses supported provider and patient perceived benefit from using PainCAS. However, as expected, no differences were found between conditions on outcome measures of pain, mood, and function. CONCLUSIONS: Results indicate that use of the PainCAS electronic pain assessment improves documentation of chart elements in clinic notes and is associated with increased discussion of key, pain-relevant topics during the clinical visit.

The Mental Status Examination.

The mental status examination includes general observations made during the clinical encounter, as well as specific testing based on the needs of the patient and physician. Multiple cognitive functions may be tested, including attention, executive functioning, gnosia, language, memory, orientation, praxis, prosody, thought content, thought processes, and visuospatial proficiency. Proprietary and open-source clinical examination tools are available, such as the Mini-Mental State Examination and the Mini-Cog. Physician judgment is necessary in selecting the most appropriate tool for an individual patient. These tools have varying sensitivity and specificity for neurologic and psychiatric disorders, but none are diagnostic for any mental status disorder. Each must be interpreted in the context of physician observation. The mental status examination is useful in helping differentiate between a variety of systemic conditions, as well as neurologic and psychiatric disorders ranging from delirium and dementia to bipolar disorder and schizophrenia. There are no guidelines to direct further testing in the setting of an abnormal mental status examination; therefore, testing is based on clinical judgment.

Prophylactic embolization versus observation for high-grade blunt trauma splenic injury: a systematic review with meta-analysis.

OBJECTIVE: The objective of this systematic review was to compare the effectiveness of prophylactic angioembolization with observation as primary management strategies for patients with high-grade (grades 3-5) blunt trauma splenic injury. INTRODUCTION: The spleen is frequently injured in abdominal trauma. Historical management practices involved splenectomy, but more recent evidence suggests an increased risk of severe infections and sepsis associated with this approach. Accordingly, non-operative management strategies, including prophylactic splenic artery embolization and clinical observation, have gained prominence. This systematic review with meta-analysis directly compares angioembolization with clinical observation for high-grade splenic injuries only, aiming to provide clarity on this matter amid ongoing debates and variations in clinical practice. INCLUSION CRITERIA: This review included adult patients aged 15 years or older with high-grade splenic injuries (grade 3-5) due to blunt trauma. Outcomes of interest include the need for further intervention (failure of management), mortality, complications, red blood cell transfusion requirements, hospital length of stay, and intensive care unit length of stay. METHODS: A comprehensive search of PubMed, Embase, and CINAHL (EBSCOhost), was performed with no restrictions on language or publication date. Gray literature was searched, including trial registries and relevant conference proceedings. After deduplication, 2 reviewers independently assessed titles and abstracts, and, subsequently, full-text articles for eligibility. Methodological quality of the included studies was assessed using standardized instruments from JBI. Data was extracted using predefined templates, and statistical meta-analysis was performed, where possible, using a random effects model. Heterogeneity was assessed using statistical methods, and potential publication bias was tested with a funnel plot. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach was used to evaluate the certainty of evidence. RESULTS: Sixteen studies were included in this review. Methodological quality assessment indicated some risk of bias in most studies, with concerns primarily related to differences in injury severity and potential confounding factors. Meta-analysis revealed that prophylactic angioembolization significantly reduced risk of management failure by 57% (OR 0.43, 95% CI 0.28-0.68, I2=53%, 15 studies) and decreased patient mortality by 37% (OR 0.63, 95% CI 0.43-0.93, I2=0%, 9 studies) compared with clinical observation alone. There was a 47% reduction in risk of complications associated with prophylactic embolization compared with clinical observation (OR 0.53, 95% CI 0.29-0.95, I2=0%, 4 studies). Some statistical heterogeneity was observed, with I2 ranging from 0% to 53%. No significant differences were observed between the 2 management strategies for red blood cell transfusion requirements and hospital length of stay. CONCLUSIONS: The results of this study support the use of prophylactic embolization for high-grade blunt trauma splenic injuries, indicated by lower failure of management rates, reduced need for additional interventions, lower mortality, and fewer complications. REVIEW REGISTRATION: PROSPERO CRD42023420220.

Effectiveness of NOTES versus traditional techniques on surgical outcomes in adults with diverticulitis: a systematic review protocol.

OBJECTIVE: This review will evaluate the effectiveness of natural orifice transluminal endoscopic surgery (NOTES)/hybrid NOTES versus traditional surgical techniques in the management of diverticular disease. INTRODUCTION: Diverticular disease can have a significant impact on a patient's quality of life, especially the changes affecting bowel function. Recurrent/severe symptoms may require surgery. Resections are invasive and can have significant operative complications. There has been a shift from an open resection to a more minimally invasive technique such as laparoscopy. Furthermore, the use of natural orifice transluminal endoscopic resection, using a transanal/transvaginal approach, has begun to be used in colorectal resections. INCLUSION CRITERIA: Eligible studies will include patients who underwent surgical resection for diverticular disease or diverticulitis. The review will consider studies that evaluate NOTES in the management of diverticular disease or diverticulitis. This will include hybrid procedures involving both NOTES and natural orifice specimen extraction (NOSE), with the aid of laparoscopy/endoscopy/robotic equipment. Studies on participants under 18 years of age and presenting with non-diverticular pathologies will be excluded. METHODS: This review will follow the JBI methodology for systematic reviews of effectiveness and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement. Databases to be searched will include PubMed, MEDLINE (Ovid), CINAHL (EBSCOhost), Cochrane Library, Web of Science, Scopus, ProQuest, ClinicalTrials.gov, and ANZCTR, with no language limitations. The reference lists of included studies will be screened for additional studies. This review will preferentially consider experimental and quasi-experimental study designs. Two reviewers will conduct critical appraisal and data extraction. Studies will, where possible, be pooled in statistical meta-analyses. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42023420771.

Randomized evaluation of a school-based, trauma-informed group intervention for young women in Chicago.

This study explores whether a school-based group counseling program for adolescent girls, implemented at scale, can mitigate trauma-related mental health harms. In a randomized trial involving 3749 Chicago public high school girls, we find that participating in the program for 4 months induces a 22% reduction in posttraumatic stress disorder symptoms and find significant decreases in anxiety and depression. Results surpass widely accepted cost-effectiveness thresholds, with estimated cost-utility well below $150,000 per quality adjusted life year. We find suggestive evidence that effects persist and may even increase over time. Our results provide the first efficacy trial of such a program specifically designed for girls, conducted in America's third largest city. These findings suggest the promise of school-based programs to mitigate trauma-related harms.

Evaluation and treatment of the suicidal patient.

Evaluation and treatment of a suicidal patient are challenging tasks for the physician. Because no validated predictive tools exist, clinical judgment guides the decision-making process. Although there is insufficient evidence to support routine screening, evidence shows that asking high-risk patients about suicidal intent leads to better outcomes and does not increase the risk of suicide. Important elements of the history that permit evaluation of the seriousness of suicidal ideation include the intent, plan, and means; the availability of social support; previous suicide attempts; and the presence of comorbid psychiatric illness or substance abuse. After intent has been established, inpatient and outpatient management should include ensuring patient safety and medical stabilization; activating support networks; and initiating therapy for psychiatric diseases. Care plans for patients with chronic suicidal ideation include these same steps, as well as referral for specialty care. In the event of a completed suicide, physicians should provide support for family members who may be experiencing grief complicated by guilt, while also activating their own support networks and risk management systems.

Treatment of childhood and adolescent depression.

Major depressive disorder in children and adolescents is a common condition that affects physical, emotional, and social development. Risk factors include a family history of depression, parental conflict, poor peer relationships, deficits in coping skills, and negative thinking. Diagnostic criteria are the same for children and adults, with the exception that children and adolescents may express irritability rather than sad or depressed mood, and weight loss may be viewed in terms of failure to reach appropriate weight milestones. Treatment must take into account the severity of depression, suicidality, developmental stage, and environmental and social factors. Cognitive behavior therapy and interpersonal therapy are recommended for patients with mild depression and are appropriate adjuvant treatments to medication in those with moderate to severe depression. Pharmacotherapy is recommended for patients with moderate or severe depression. Tricyclic antidepressants are not effective in children and adolescents. Antidepressants have a boxed warning for the increased risk of suicide; therefore, careful assessment, follow-up, safety planning, and patient and family education should be included when treatment is initiated.

New paradigm in nutrition support: using evidence to drive practice.

Adequate nutrition support is a key component in achieving favorable outcomes for the critically ill patient. Significant evidence supports starting enteral nutrition rather than parenteral nutrition as early as possible after injury to promote positive outcomes. Evidence shows that enteral nutrition improves patient outcomes and decreases intensive care unit length of stay by improving splanchnic blood flow, moderating the metabolic response, sustaining gut integrity, and preventing bacterial translocation from the gut to the bloodstream. Implementing early enteral nutrition can be challenging. This article describes the rationale for early enteral nutrition, the evidence that favors enteral nutrition over parenteral nutrition, barriers to delivery of full enteral nutrition, and an evidence-based protocol developed at Harborview Medical Center to promote appropriate support. The role of the registered dietitian on the health care team in facilitating appropriate feeding is discussed. In addition, we will describe emerging nutrition therapies including the use of antioxidants, addition of the amino acid glutamine, use of immune-enhancing enteral formulas, and the potential role of probiotics that show promise in improving patient outcome.

Evaluating Changes in Family Medicine Applicant Characteristics Following the Onset of Virtual Interviewing.

BACKGROUND AND OBJECTIVES: The COVID-19 pandemic obliged the field of graduate medical education to pivot from in-person to virtual residency interviews in 2020. The decreased travel and financial barriers of this format could potentially lead to greater diversity and equity in the primary care workforce. We aimed to evaluate changes in applicant pools from in-person to virtual interviewing cycles. METHODS: We conducted a retrospective review of Electronic Residency Application Services (ERAS) from five US family medicine residencies across five interview cycles (three in-person and two virtual; 2017/2018 through 2021/2022). We compared geographic and demographic data about applicants as well as administrative program data. RESULTS: The study included 25,271 applicants. The average distance between applicants and programs was 768 miles during in-person interview years and 772 miles during virtual interview years (P=.27). Applicants who interviewed with programs were 446 and 459 miles away, respectively (P=.06). During in-person application years, applicants with backgrounds historically underrepresented in medicine (URM) submitted an average of 21% of applications; this increased approximately 1% during virtual interviewing years (OR, 1.08; P=.03). There were no other differences between in-person and virtual application years in rates of URM applicants. Residency programs received more applications from US medical schools (OR, 1.46; P<.0001) and were more likely to interview a US medical school applicant (OR, 2.26; P<.0001) in virtual years. Program fill rates appeared to be lower during virtual years. CONCLUSIONS: The virtual interviewing format did not appear to substantially increase the geographic, racial, or ethnic diversity of applicants, and was associated with increased applications from US medical schools.

Toward sustainable syntheses of Ca-based MOFs.

We report the use of benign and green precursors, including waste chicken eggshells and PET (polyethylene terephthalate) from recycled plastic bottles, for the facile synthesis of a variety of calcium-based metal-organic frameworks (Ca-MOFs), using water based and mechanochemical synthesis techniques.

Top 10 Facts You Need to Know About Synthetic Cannabinoids: Not So Nice Spice.

In April and May 2015, the state of Mississippi experienced an unprecedented outbreak of severe reactions to the drug commonly referred to as "Spice." After numerous calls to the Poison Control Center, it became clear that health care providers were largely unfamiliar with the category of synthetic cannabinoids. This review article briefly highlights cannabinoid effects, chemical characteristics, and treatment for this often-dangerous category of drugs of abuse.

Social desirability, defense styles, and the Children's Role Inventory scale.

This investigation was designed to answer several research questions. First, using each participant's dominant score to place that individual into one of the four Children's Role Inventory categories, what would be the distribution of college students across the categories? Second, is there a relationship between scores on scales of the Children's Role Inventory and (a) on the Marlowe-Crowne Social Desirability Scale and (b) on scales of the Defense Style Questionnaire? 236 undergraduate students at a southern university completed the above questionnaires. The distribution of participants over Children's Role Inventory categories was Hero 179, Mascot 41, Scapegoat 1, Lost Child 9, and Not Classified 6. After Bonferroni correction, significant positive but small correlations were reported between the Hero Scale of the Children's Role Inventory and the Marlowe-Crowne Social Desirability Scale, as well as between the Hero Scale of the Children's Role Inventory and the Adaptive Scale of the Defense Style Questionnaire.

Measuring rodent electroretinograms to assess retinal function.

Electroretinography is a noninvasive technique used to measure the electrical activity of neurons in the retina. Electroretinogram (ERG) waveforms can be used to quantify retinal function in normal and diseased rodents. In particular, the functions of rod and cone pathways can be isolated. Inner retinal neuronal functioning, such as bipolar cell activity or ganglion cell activity, can also be measured. In this chapter we describe the common full-field ERG techniques of scoptic flash, photopic flash, and flicker used to isolate and compare rod-driven and cone-driven function.

Depression, screening and quality of life in chronic kidney disease.

INTRODUCTION: To determine the prevalence of positive screens for depression and to assess quality of life (QoL) and usefulness of the brief and easily administered Patient Health Questionnaire-2 (PHQ-2) for depression screening in the chronic kidney disease (CKD) population; and to explore the relationship between depressive symptoms and markers of inflammation. METHODS: Seventy-one adult patients with estimated glomerular filtration rate <60 mL/min/1.73 m or proteinuria, but not on dialysis, were enrolled. QoL was assessed using the Short Form-36. The Center for Epidemiological Studies Depression Scale (CES-D) and PHQ-2 were used to screen for depression. Serum ferritin, albumin, C-reactive protein and hematocrit were also measured as markers of inflammation. RESULTS: The PHQ-2 and CES-D were significantly correlated (P < 0.05). Positive scores on the CES-D or PHQ-2 had significantly lower Short Form-36 scores. Mean hemoglobin values were significantly lower in patients who screened positive for depression either by CES-D (12.2 ± 1.7 versus 13.2 ± 1.7, P < 0.05) or by PHQ-2 (12 ± 1.6 versus 13.4 ± 1.6, P < 0.01). Neither PHQ-2 nor CES-D correlated with other markers of inflammation in this sample. CONCLUSION: Both the CES-D and the PHQ-2 can identify patients with CKD who need further evaluation for depression. The PHQ-2 seems to be a useful screen for depression and impaired QoL in a renal clinic setting. Patients with CKD and lower hemoglobin may be at greater risk for depression than those with normal values.