Barriers and proposed solutions to at-home colorectal cancer screening tests in medically underserved health centers across three US regions to inform a randomized trial.

INTRODUCTION: At-home colorectal cancer (CRC) screening is an effective way to reduce CRC mortality, but screening rates in medically underserved groups are low. To plan the implementation of a pragmatic randomized trial comparing two population-based outreach approaches, we conducted qualitative research on current processes and barriers to at-home CRC screening in 10 community health centers (CHCs) that serve medically underserved groups, four each in Massachusetts and California, and two tribal facilities in South Dakota. METHODS: We conducted 53 semi-structured interviews with clinical and administrative staff at the participating CHCs. Participants were asked about CRC screening processes, categorized into eight domains: patient identification, outreach, risk assessment, fecal immunochemical test (FIT) workflows, FIT-DNA (i.e., Cologuard) workflows, referral for a follow-up colonoscopy, patient navigation, and educational materials. Transcripts were analyzed using a Rapid Qualitative Analysis approach. A matrix was used to organize and summarize the data into four sub-themes: current process, barriers, facilitators, and solutions to adapt materials for the intervention. RESULTS: Each site's process for stool-based CRC screening varied slightly. Interviewees identified the importance of offering educational materials in English and Spanish, using text messages to remind patients to return kits, adapting materials to address health literacy needs so patients can access instructions in writing, pictures, or video, creating mailed workflows integrated with a tracking system, and offering patient navigation to colonoscopy for patients with an abnormal result. CONCLUSION: Proposed solutions across the three regions will inform a multilevel intervention in a pragmatic trial to increase CRC screening uptake in CHCs.

The Revised United States Preventive Services Task Force Screening Recommendations and Racial/Ethnic Differences in Colorectal Cancer Screening in a Boston Healthcare System.

INTRODUCTION: To evaluate the impact of the updated United States Preventive Services Task Force colorectal cancer (CRC) screening recommendations on screening rates in a large health system. METHODS: We reviewed Massachusetts General Brigham electronic health record data for individuals eligible for CRC screening between January 3, 2020, and January 5, 2023, and calculated whether age-eligible individuals were up-to-date with CRC screening. RESULTS: There were large declines in the percentage of individuals who were up-to-date with CRC screening for all racial/ethnic groups, with non-Hispanic Asians being largest (-13.5%). DISCUSSION: Health systems should implement culturally tailored strategies to reach and screen newly eligible individuals for CRC screening to prevent worsening disparities in CRC.

Community collaboration to advance racial/ethnic equity in colorectal Cancer screening: Protocol for a multilevel intervention to improve screening and follow-up in community Health centers.

INTRODUCTION: Colorectal cancer (CRC) screening utilization is low among low-income, uninsured, and minority populations that receive care in community health centers (CHCs). There is a need for evidence-based interventions to increase screening and follow-up care in these settings. METHODS: A multilevel, multi-component pragmatic cluster randomized controlled trial is being conducted at 8 CHCs in two metropolitan areas (Boston and Los Angeles), with two arms: (1) Mailed FIT outreach with text reminders, and (2) Mailed FIT-DNA with patient support. We also include an additional CHC in Rapid City (South Dakota) that follows a parallel protocol for FIT-DNA but is not randomized due to lack of a comparison group. Eligible individuals in participating clinics are primary care patients ages 45-75, at average-risk for CRC, and overdue for CRC screening. Participants with abnormal screening results are offered navigation for follow-up colonoscopy and CRC risk assessment. RESULTS: The primary outcome is the completion rate of CRC screening at 90 days. Secondary outcomes include the screening completion rate at 180 days and the rate of colonoscopy completion within 6 months among participants with an abnormal result. Additional goals are to enhance our understanding of facilitators and barriers to CRC risk assessment in CHC settings. CONCLUSIONS: This study assesses the effectiveness of two multilevel interventions to increase screening participation and follow-up after abnormal screening in under-resourced clinical settings, informing future efforts to address CRC disparities. TRIAL REGISTRATION: NCT05714644.

Vulnerability and Colorectal screening during the pandemic.

Objective: Disparities in colorectal cancer (CRC) screening prevalence across United States neighborhoods may reflect social inequities that create barriers to accessing and completing preventive health services. Our objective was to identify whether neighborhood social vulnerability was associated with a change in CRC screening prevalence in Boston neighborhoods during the COVID-19 pandemic. Methods: Adults ages 50-74 years due for CRC screening who received primary care at one of 35 primary care practices affiliated with Massachusetts General Hospital or Brigham and Women's Hospital (Boston, MA), 3/1/2020 to 3/1/2022. The Social Vulnerability Index (SVI) is an aggregate measure of neighborhood social factors often used by public health authorities to examine neighborhood susceptibility to many health outcomes. Results: In 2020, 74.9 % of eligible individuals were up to date with CRC screening and this fell to 67.4 % in 2022 (p < 0.001). In 2020, 36.2 % of eligible patients lived in a neighborhood above the 80th percentile of SVI, consistent with high social vulnerability, while the same value was 35.1 % in 2022. There was no association between the change in screening prevalence and SVI: a decrease of 5.5 % screened in neighborhoods with SVI ≤ 80 compared to a decrease of 3.6 % in neighborhoods with SVI > 80 (p = 0.79). Conclusions: The COVID-19 pandemic equalized the prevalence of CRC screening across Boston-area neighborhoods despite pre-existing geographic disparities in screening prevalence and SVI. Strategies to ensure equitable participation in CRC screening to promote health equity should be considered to promote equitable pandemic recovery.

Spotlight on the pediatric eye: a pictorial review of orbital anatomy and congenital orbital pathologies.

Orbital lesions in the pediatric population vary from adults in terms of their presentation, unique pathology, and imaging characteristics. The prompt and accurate diagnosis of these lesions is imperative to prevent serious consequences in terms of visual impairment and disfigurement. Along with dedicated ophthalmologic examination, imaging is instrumental in characterizing these lesions, both for accurate diagnosis and subsequent management. In our pictorial essay, we provide a basic review of orbital embryology, anatomy, and congenital orbital pathologies, with emphasis on radiological findings.

Magnetic resonance imaging criteria of immune checkpoint inhibitor-induced hypophysitis.

Autoimmune hypophysitis is a rare complication of immune checkpoint inhibitors. Immune checkpoint inhibitors have been used for advanced stages of melanoma, renal cell carcinoma, and lung cancer. Multiple endocrinopathies, among them hypophysitis, could result as a reverse event from this therapy. MRI is the imaging modality of choice and usually demonstrates pituitary gland hypertrophy, irregular thickening of the pituitary infundibulum, and diffuse enhancement. We present a case of stage IV metastatic renal cell carcinoma complicated with hypophysitis secondary to combined nivolumab and ipilimumab therapy.

Activity Within an Extraperitoneal Ureteral Herniation Detected on Bone Scan, Associated With a Partially Duplicated Collecting System.

A 64-year-old man with history of renal stones and prostate cancer presented for evaluation of osseous metastatic disease due to elevated prostate-specific antigen (13.7 ng/mL). A Tc-labeled bone scan demonstrated unusual linear uptake projecting over the lower pelvis extending into the scrotum. Follow-up CT confirmed a rare case of inguinoscrotal extraperitoneal herniation of the ureter associated with a partially duplicated left renal collecting system. The left-sided inguinoscrotal uptake was within the herniated ureter, potentially mimicking disease within the pelvis.

Appendiceal diverticulosis in a patient with family history of Birt-Hogg-Dubé syndrome--a case report.

Birt-Hogg-Dubé syndrome (BHD) is a rare autosomal dominant disorder that predisposes patients to cutaneous tumors, pulmonary cysts with recurrent spontaneous pneumothoraces, and a variety of renal neoplasms including hybrid oncocytic and chromophobe renal cell carcinomas. There has been much debate regarding the genetic link with the occurrence of colorectal cancer and other colonic anomalies. Associations between BHD and intestinal adenomatous polyposis and sigmoid diverticulosis have been described in the literature, but there have been no prior reports of appendiceal diverticulosis in patients with BHD. Here, we present a 40-year-old female patient with a known family history of BHD, who was found to have diverticulosis of the appendix and pulmonary blebs on computed tomography upon routine screening for renal and pulmonary abnormalities, suggesting additional focus be given to the gastrointestinal tract (including the appendix) at the time of CT assessment.

Spontaneous hemorrhage of an adrenal myelolipoma treated with transarterial embolization: A case report.

Adrenal myelolipoma is a benign tumor of the adrenal cortex composed predominantly of fat and hematopoietic tissue. These lesions are usually asymptomatic, and most often incidentally detected on imaging. Uncommonly, they present with retroperitoneal hemorrhage, and these have been traditionally treated with emergent surgery. Although, transarterial embolization has been effectively and safely used in patients presenting with active hemorrhage from acute traumatic and nontraumatic causes, literature specifically pertaining to adrenal artery embolization is scant, perhaps due to smaller size and variability of adrenal arteries. With recent advances in endovascular techniques and imaging, there are emerging case reports and series of adrenal artery embolization in acute and nonacute settings. We report a case of spontaneous hemorrhage within an adrenal myelolipoma in a 43-year-old male patient, successfully treated with transarterial embolization, thereby avoiding major surgery. Our report adds to the growing body of literature pertaining to adrenal artery embolization.

Metastatic appendiceal cancer treated with Yttrium 90 radioembolization and systemic chemotherapy: A case report.

BACKGROUND: Primary appendiceal cancers are rare, and they generally present with liver and/or peritoneal metastases. Currently there are no guidelines to treat metastatic appendiceal cancer, and hence they are treated as metastatic colorectal cancer. Combining Yttrium 90 (Y-90) radioembolization (RE) with systemic chemotherapy early in the treatment of right sided colon cancers has been shown to improve survival. Based on this data, a combination of systemic chemotherapy and Y-90 RE was used to treat a case of metastatic appendiceal cancer. CASE SUMMARY: A 76-year-old male presented to the emergency room with progressive right lower quadrant pain. A Computed Tomography of the abdomen and pelvis was performed which showed acute appendicitis and contained perforation. Urgent laparoscopic appendectomy was then followed by histological analysis, which was significant for appendiceal adenocarcinoma. After complete workup he underwent right hemicolectomy and lymph node dissection. He received adjuvant chemotherapy as the local lymph nodes were positive. Follow-up imaging was significant for liver metastasis. Due to rapid growth of the liver lesions and new peritoneal nodules, the patient was treated with a combination of Y-90 RE and folinic acid, fluorouracil, and irinotecan with bevacizumab and not microwave ablation as previously planned. Follow up imaging demonstrated complete response of the liver lesions. At 12-mo follow-up, the patient continued to enjoy good quality of life with no recurrent disease. CONCLUSION: Utilization of Y-90 RE concomitantly with systemic chemotherapy early in the treatment of appendiceal cancer may provide improved control of this otherwise aggressive cancer.

Amelioration of ongoing experimental autoimmune encephalomyelitis with fluoxetine.

In patients with multiple sclerosis, the selective serotonin reuptake inhibitor, fluoxetine, resulted in less acute disease activity. We tested the immune modulating effects of fluoxetine in a mouse model of multiple sclerosis, i.e. experimental autoimmune encephalomyelitis (EAE). We show that fluoxetine delayed the onset of disease and reduced clinical paralysis in mice with established disease. Fluoxetine had abrogating effects on proliferation of immune cells and inflammatory cytokine production by both antigen-presenting cells and T cells. Specifically, in CD4 T cells, fluoxetine increased Fas-induced apoptosis. We conclude that fluoxetine possesses immune-modulating effects resulting in the amelioration of symptoms in EAE.

Peroxisome proliferator-activated receptor delta limits the expansion of pathogenic Th cells during central nervous system autoimmunity.

Peroxisome proliferator-activated receptors (PPARs; PPAR-alpha, PPAR-delta, and PPAR-gamma) comprise a family of nuclear receptors that sense fatty acid levels and translate this information into altered gene transcription. Previously, it was reported that treatment of mice with a synthetic ligand activator of PPAR-delta, GW0742, ameliorates experimental autoimmune encephalomyelitis (EAE), indicating a possible role for this nuclear receptor in the control of central nervous system (CNS) autoimmune inflammation. We show that mice deficient in PPAR-delta (PPAR-delta(-/-)) develop a severe inflammatory response during EAE characterized by a striking accumulation of IFN-gamma(+)IL-17A(-) and IFN-gamma(+)IL-17A(+) CD4(+) cells in the spinal cord. The preferential expansion of these T helper subsets in the CNS of PPAR-delta(-/-) mice occurred as a result of a constellation of immune system aberrations that included higher CD4(+) cell proliferation, cytokine production, and T-bet expression and enhanced expression of IL-12 family cytokines by myeloid cells. We also show that the effect of PPAR-delta in inhibiting the production of IFN-gamma and IL-12 family cytokines is ligand dependent and is observed in both mouse and human immune cells. Collectively, these findings suggest that PPAR-delta serves as an important molecular brake for the control of autoimmune inflammation.

Inhibitory role for GABA in autoimmune inflammation.

GABA, the principal inhibitory neurotransmitter in the adult brain, has a parallel inhibitory role in the immune system. We demonstrate that immune cells synthesize GABA and have the machinery for GABA catabolism. Antigen-presenting cells (APCs) express functional GABA receptors and respond electrophysiologically to GABA. Thus, the immune system harbors all of the necessary constituents for GABA signaling, and GABA itself may function as a paracrine or autocrine factor. These observations led us to ask further whether manipulation of the GABA pathway influences an animal model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE). Increasing GABAergic activity ameliorates ongoing paralysis in EAE via inhibition of inflammation. GABAergic agents act directly on APCs, decreasing MAPK signals and diminishing subsequent adaptive inflammatory responses to myelin proteins.

Innate and adaptive autoimmunity directed to the central nervous system.

The immune system has two major components, an innate arm and an adaptive arm. Certain autoimmune diseases of the brain represent examples of disorders where one of these constituents plays a major role. Some rare autoimmune diseases involve activation of the innate arm and include chronic infantile neurologic, cutaneous, articular (CINCA) syndrome. In contrast, adaptive immunity is prominent in multiple sclerosis, neuromyelitis optica, and the paraneoplastic syndromes where highly specific T cell responses and antibodies mediate these diseases. Studies of autoimmune brain disorders have aided in the elucidation of distinct neuronal roles played by key molecules already well known to immunologists (e.g., complement and components of the major histocompatibility complex). In parallel, molecules known to neurobiology and sensory physiology, including toll-like receptors, gamma amino butyric acid and the lens protein alpha B crystallin, have intriguing and distinct functions in the immune system, where they modulate autoimmunity directed to the brain.