Challenges and Opportunities in the Elective Management of Diverticulitis: Perspectives From a National Sample of Colorectal Surgeons.

BACKGROUND: Diverticulitis is a complex, heterogeneous disease process that affects a diverse population of patients. In the elective management of this disease, treatment guidelines have shifted toward patient-centered, individualized decision-making. It is not known what challenges surgeons face as they approach these nuanced treatment decisions in practice. OBJECTIVE: This study aimed to identify opportunities to support colorectal surgeons in elective diverticulitis treatment. DESIGN: This was a qualitative study using standardized, semistructured interviews to explore the perspectives of 29 colorectal surgeons recruited using a purposive sampling technique. Data were analyzed using an "open-coding" approach. SETTINGS: Interviews with a national sample of colorectal surgeons were conducted from a single center using an online video platform. PATIENTS: This study did not involve patients. MAIN OUTCOME MEASURES: Interviews explored surgeons' experiences treating diverticulitis in the elective setting, focusing on perceived challenges in providing patient-centered care as well as opportunities to improve treatment decisions. RESULTS: Our qualitative analysis identified an overarching challenge in elective diverticulitis management for surgeons: difficulty ensuring adequate patient understanding of the risks and benefits of various treatments. This was thought to be due to 1) preexisting patient expectations about treatment and 2) lack of data regarding long-term treatment outcomes. Surgeons identified 2 potential opportunities to combat these challenges: 1) patient education and 2) additional research regarding treatment outcomes, with potential for the development of diverticulitis-specific decision support tools. LIMITATIONS: These results are based on a national sample of colorectal surgeons, but they capture qualitative data that is not intended to provide generalizable findings. CONCLUSIONS: As surgeons work toward providing individualized care for diverticulitis patients, they find it difficult to adequately counsel patients regarding the patient-specific risks of various treatments. The results of this study identify specific contributors to this problem as well as potential targets for intervention, which can guide future efforts to support surgeons in providing patient-centered care. See Video Abstract . DESAFOS Y OPORTUNIDADES EN EL MANEJO ELECTIVO DE LA DIVERTICULITIS PERSPECTIVAS DE UNA MUESTRA NACIONAL DE CIRUJANOS COLORRECTALES: ANTECEDENTES:La diverticulitis es un proceso patológico complejo y heterogéneo que afecta a una población diversa de pacientes. En el manejo electivo de esta enfermedad, las pautas de tratamiento se han desplazado hacia una toma de decisiones individualizada y centrada en el paciente. No se sabe qué desafíos enfrentan los cirujanos al abordar estas decisiones de tratamiento matizadas en la práctica.OBJETIVO:Identificar oportunidades para apoyar a los cirujanos colorrectales en el tratamiento electivo de la diverticulitis.DISEÑO:Este fue un estudio cualitativo que utilizó entrevistas semiestructuradas estandarizadas para explorar las perspectivas de 29 cirujanos colorrectales reclutados mediante una técnica de muestreo intencional. Los datos se analizaron utilizando un enfoque de "codificación abierta".ESCENARIO:Las entrevistas con una muestra nacional de cirujanos colorrectales se realizaron desde un solo centro utilizando una plataforma de video en línea.PRINCIPALES MEDIDAS DE RESULTADO:Las entrevistas exploraron las experiencias de los cirujanos en el tratamiento de la diverticulitis en el entorno electivo, centrándose en los desafíos percibidos en la prestación de atención centrada en el paciente, así como en las oportunidades para mejorar las decisiones de tratamiento.RESULTADOS:Nuestro análisis cualitativo identificó un desafío general en el manejo de la diverticulitis electiva para los cirujanos: la dificultad para asegurar que el paciente comprenda adecuadamente los riesgos y beneficios de los diversos tratamientos. Se pensó que esto se debía a 1) las expectativas preexistentes del paciente sobre el tratamiento y 2) la falta de datos sobre los resultados del tratamiento a largo plazo. Los cirujanos identificaron dos oportunidades potenciales para combatir estos desafíos: 1) educación del paciente y 2) investigación adicional sobre los resultados del tratamiento, con potencial para el desarrollo de herramientas de apoyo a la toma de decisiones específicas para la diverticulitis.LIMITACIONES:Estos resultados se basan en una muestra nacional de cirujanos colorrectales, pero capturan datos cualitativos que no pretenden proporcionar hallazgos generalizables.CONCLUSIONES:A medida que los cirujanos trabajan para brindar atención individualizada a los pacientes con diverticulitis, les resulta difícil aconsejar adecuadamente a los pacientes sobre los riesgos específicos de los pacientes para los diversos tratamientos. Los resultados de este estudio identifican contribuyentes específicos a este problema, así como objetivos potenciales para la intervención, que pueden guiar los esfuerzos futuros para ayudar a los cirujanos a brindar atención centrada en el paciente. (Traducción-Dr. Felipe Bellolio ).

Surgical Trainee Perspectives on the Opioid Crisis: The Influence of Explicit and Hidden Curricula.

OBJECTIVE: In order to effectively create and implement an educational program to improve opioid prescribing practices, it is important to first consider the unique perspectives of residents on the frontlines of the opioid epidemic. We sought to better understand resident perspectives on opioid prescribing, current practices in pain management, and opioid education as a needs assessment for designing future educational interventions. DESIGN: This is a qualitative study using focus groups of surgical residents at 4 different institutions. SETTING: We conducted focus groups using a semistructured interview guide in person or over video conferencing. The residency programs selected for participation represent a broad geographic range and varying residency sizes. PARTICIPANTS: We used purposeful sampling to recruit general surgery residents from the University of Utah, University of Wisconsin, Dartmouth-Hitchcock Medical Center, and the University of Alabama at Birmingham. All general surgery residents at these locations were eligible for inclusion. Participants were assigned to focus groups by residency site and their status as junior (PGY-2, PGY-3) or senior resident (PGY-4, PGY-5). RESULTS: We completed 8 focus groups with a total of 35 residents included. We identified 4 main themes. First, residents relied on clinical and nonclinical factors when making decisions about opioid prescribing. However, hidden curricula based on unique institutional cultures and attending preferences heavily influenced residents' prescribing practices. Second, residents acknowledged that stigma and biases towards certain patient groups influenced opioid prescribing practices. Third, residents encountered barriers within their health systems to evidence-based opioid prescribing. Fourth, residents did not routinely receive formal education on pain management or opioid prescribing. Residents recommended several interventions to improve the current state of opioid prescribing, including standardized prescribing guidelines, improved patient education, and formal training during the first year of residency. CONCLUSIONS: Our study highlighted several areas of opioid prescribing that can be improved upon through educational interventions. These findings can be used to develop programs aimed at improving residents' opioid prescribing practices, both during and after training, and ultimately the safe care of surgical patients. ETHICS STATEMENT: This project was approved by the University of Utah Institutional Review Board, ID # 00118491. All participants provided written informed consent.

The Influence of Rural Healthcare Systems and Communities on Surgery and Recovery: A Qualitative Study.

INTRODUCTION: Successful recovery after surgery is complex and highly individual. Rural patients encounter greater barriers to successful surgical recovery than urban patients due to varying healthcare and community factors. Although studies have previously examined the recovery process, rural patients' experiences with recovery have not been well-studied. The rural socioecological context can provide insights into potential barriers or facilitators to rural patient recovery after surgery. METHODS: We conducted semi-structured qualitative interviews with a purposeful sample of 30 adult general surgery patients from rural areas in the Mountain West region of the United States. We used the socioecological framework to analyze their responses. Interviews focused on rural participants' experiences accessing healthcare and the impact of family and community support during postoperative recovery. Interviews were transcribed verbatim and coded using content and thematic analysis. RESULTS: All participants commented on the quality of their rural healthcare systems and its influence on postoperative care. Some enjoyed the trust developed through long-standing relationships with providers in their communities. However, participants described community providers' lack of money, equipment, and/or knowledge as barriers to care. Following surgery, participants recognized that there are advantages and disadvantages to receiving family and community support. Some participants worried about being stigmatized or judged by their community. CONCLUSIONS: Future interventions aimed at improving access to and recovery from surgery for rural patients should take into account the unique perspectives of rural patients. Addressing the socioecological factors surrounding rural surgery patients, such as healthcare, family, and community resources, will be key to improving postoperative recovery.

Socioeconomic disadvantage is associated with greater mortality after high-risk emergency general surgery.

BACKGROUND: Socioeconomic disadvantage is associated with worse outcomes after elective surgery, but the effect on emergency general surgery (EGS) remains unclear. We examined the association of socioeconomic disadvantage and outcomes after EGS procedures and investigated whether admission to hospitals with comprehensive clinical and social resources mitigated this effect. METHODS: Adults undergoing 1 of the 10 most burdensome high- and low-risk EGS procedures were identified in six 2014 State Inpatient Databases. Socioeconomic disadvantage was assessed using Area Deprivation Index (ADI) of patient residence. Multivariable logistic regression models adjusting for patient and hospital factors were used to evaluate the association between ADI quartile (high >75 percentile vs. low <25 percentile), and 30-day readmission, in-hospital mortality, and discharge disposition. Effect modification between ADI and (a) level 1 trauma center and (b) safety-net hospital status was tested. RESULTS: A total of 103,749 patients were analyzed: 72,711 low-risk (70.1%) and 31,038 high-risk procedures (29.9%). Patients from neighborhoods with high socioeconomic disadvantage had a higher proportion with ≥3 comorbidities (41.9% vs. 32.0%), minority race/ethnicity (66.3% vs. 42.4%), and Medicaid (28.8% vs. 14.7%) and were less likely to be treated at level 1 trauma centers (18.3% vs. 27.7%; p < 0.001 for all). Adjusting for competing factors, high socioeconomic disadvantage was associated with increased in-hospital mortality after high-risk procedures (odd ratio, 1.30; 95% confidence interval, 1.01-1.66; p = 0.04) and higher odds of non-home discharge (odd ratio, 1.15; 95% confidence interval, 1.02-1.30; p = 0.03) for low-risk procedures. Socioeconomic disadvantage was not associated with 30-day readmission for either procedure group. Level 1 trauma status and safety-net hospital did not meaningfully mitigate effect of ADI for any outcome. CONCLUSION: Socioeconomic disadvantage is associated with increased mortality after high-risk procedures and higher odds of non-home discharge after low-risk procedures. This effect was not mitigated by either level 1 trauma or safety-net hospitals. Interventions that specifically address the needs of socially vulnerable communities will be required to significantly improve EGS outcomes for this population. LEVEL OF EVIDENCE: Prognostic and Epidemiologic, level III.

Use of post-discharge opioid consumption patterns as a tool for evaluating opioid prescribing guidelines.

BACKGROUND: Leftover pills from postoperative opioid prescriptions place patients and members of their communities at risk for opioid misuse. We aimed to better understand patients' post-discharge opioid consumption patterns to inform new methods of postoperative opioid prescribing. METHODS: We assessed post-discharge opioid consumption of general surgery patients and assessed the adequacy of discharge opioid prescriptions. We then compared patient opioid consumption to a number of theoretical discharge prescriptions based on different opioid prescribing guidelines and a proposed discharge prescription based on the metric 24-h pre-discharge opioid consumption (PDOC). RESULTS: 62/99 patients (62.6%) returned an opioid log book. Median 24-h PDOC was 22.5 MME (IQR 5.0-45.0) and median discharge prescription size was 15 pills (IQR:10-20). Prescriptions were adequate for 83.7% of patients. The median number of pills used was 3 (IQR:0-11) and median time to opioid cessation was 3 days (IQR:0-5). Actual prescriptions were consistent with national opioid prescribing guidelines. Prescriptions based on the formula 2 × 24-h PDOC would have decreased the number of leftover pills by 7.5 per patient. CONCLUSIONS: Despite prescribing opioids consistent with national opioid prescribing guidelines, patients still receive too many pills. Improved opioid prescribing could be accomplished by use of the formula 2 × 24-h PDOC.

Benign Colonic Strictures.

CASE SUMMARY: A 46-year-old man with no significant medical or surgical history presented to the emergency department with a 1-week history of worsening constipation, abdominal distension, nausea, and nonbloody, nonbilious emesis. Workup included a CT scan that was notable for a 5.3 × 3.9 cm "apple core-type" mass located within the sigmoid colon with proximal large-bowel dilation. Carcinoembryonic antigen was 1.4. No metastatic disease was seen on chest, abdominal, or pelvic CT scans. Flexible sigmoidoscopy identified a sigmoid colon mass 30 cm from the anal verge with near complete obstruction. Biopsies of the mass did not show evidence of dysplasia or malignancy. The Gastroenterology service declined to place a stent without a malignancy diagnosis. The patient subsequently underwent exploratory laparotomy, sigmoid colectomy, and end colostomy. Recovery was uneventful. Final pathology showed diverticulitis with abscess formation and no evidence of malignancy. A completion colonoscopy was unremarkable, and the patient underwent colostomy reversal 3 months later.

Expansion of Simian Immunodeficiency Virus (SIV)-Specific CD8 T Cell Lines from SIV-Naive Mauritian Cynomolgus Macaques for Adoptive Transfer.

UNLABELLED: CD8 T cells play a crucial role in the control of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV). However, the specific qualities and characteristics of an effective CD8 T cell response remain unclear. Although targeting breadth, cross-reactivity, polyfunctionality, avidity, and specificity are correlated with HIV control, further investigation is needed to determine the precise contributions of these various attributes to CD8 T cell efficacy. We developed protocols for isolating and expanding SIV-specific CD8 T cells from SIV-naive Mauritian cynomolgus macaques (MCM). These cells exhibited an effector memory phenotype, produced cytokines in response to cognate antigen, and suppressed viral replication in vitro. We further cultured cell lines specific for four SIV-derived epitopes, Nef103-111 RM9, Gag389-394 GW9, Env338-346 RF9, and Nef254-262 LT9. These cell lines were up to 94.4% pure, as determined by major histocompatibility complex (MHC) tetramer analysis. After autologous transfer into two MCM recipients, expanded CD8 T cells persisted in peripheral blood and lung tissue for at least 24 weeks and trafficked to multiple extralymphoid tissues. However, these cells did not impact the acute-phase SIV load after challenge compared to historic controls. The expansion and autologous transfer of SIV-specific T cells into naive animals provide a unique model for exploring cellular immunity and the control of SIV infection and facilitate a systematic evaluation of therapeutic adoptive transfer strategies for eradication of the latent reservoir. IMPORTANCE: CD8 T cells play a crucial role in the control of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV). Autologous adoptive transfer studies followed by SIV challenge may help define the critical elements of an effective T cell response to HIV and SIV infection. We developed protocols for isolating and expanding SIV-specific CD8 T cells from SIV-naive Mauritian cynomolgus macaques. This is an important first step toward the development of autologous transfer strategies to explore cellular immunity and potential therapeutic applications in the SIV model.

Whole genome sequencing of SIV-infected macaques identifies candidate loci that may contribute to host control of virus replication.

BACKGROUND: A small percentage of human immunodeficiency virus (HIV)-infected people and simian immunodeficiency virus (SIV)-infected macaques control virus replication without antiretroviral treatment. The major determinant of this control is host expression of certain major histocompatibility complex alleles. However, this association is incompletely penetrant, suggesting that additional loci modify the major histocompatibility complex's protective effect. Here, to identify candidate control-modifying loci, we sequence the genomes of 12 SIV-infected Mauritian cynomolgus macaques that experienced divergent viral load set points despite sharing the protective M1 major histocompatibility complex haplotype. RESULTS: Our genome-wide analysis of haplotype-level variation identifies seven candidate control-modifying loci on chromosomes 2, 3, 7, 8, 9, 10, and 14. The highest variant density marks the candidate on chromosome 7, which is the only control-modifying locus to comprise genes with known immunological function. Upon closer inspection, we found an allele for one of these genes, granzyme B, to be enriched in M1(+) controllers. Given its established role as a cytotoxic effector molecule that participates in CD8-mediated killing of virus-infected cells, we test the role of variation within gzmb in modifying SIV control by prospectively challenging M1(+) granzyme B-defined macaques. CONCLUSIONS: Our study establishes a framework for using whole genome sequencing to identify haplotypes that may contribute to complex clinical phenotypes. Further investigation into the immunogenetics underlying spontaneous HIV control may contribute to the rational design of a vaccine that prevents acquired immune deficiency syndrome.

Rapid, repeated, low-dose challenges with SIVmac239 infect animals in a condensed challenge window.

BACKGROUND: Simian immunodeficiency virus (SIV) infection of nonhuman primates is the predominant model for preclinical evaluation of human immunodeficiency virus (HIV) vaccines. These studies frequently utilize high-doses of SIV that ensure infection after a single challenge but do not recapitulate critical facets of sexual HIV transmission. Investigators are increasingly using low-dose challenges in which animals are challenged once every week or every two weeks in order to better replicate sexual HIV transmission. Using this protocol, some animals require over ten challenges before SIV infection is detectable, potentially inducing localized immunity. Moreover, the lack of certainty over which challenge will lead to productive infection prevents tissue sampling immediately surrounding the time of infection. FINDINGS: Here we challenged Mauritian cynomolgus macaques with 100 50% tissue culture infectious doses (TCID50) of SIVmac239 intrarectally three times a day for three consecutive days. Ten of twelve animals had positive plasma viral loads after this challenge regimen. CONCLUSIONS: This approach represents a straightforward advance in SIV challenge protocols that may avoid induction of local immunity, avoid inconsistent timing between last immunization and infection, and allow sampling immediately after infection using low-dose challenge protocols.

T cell response specificity and magnitude against SIVmac239 are not concordant in major histocompatibility complex-matched animals.

BACKGROUND: CD8+ T cell responses, restricted by major histocompatibility complex (MHC) class I molecules, are critical to controlling human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV) replication. Previous studies have used MHC-matched siblings and monozygotic twins to evaluate genetic and stochastic influences on HIV-specific T cell responses and viral evolution. Here we used a genetically restricted population of Mauritian cynomolgus macaques (MCM) to characterize T cell responses within nine pairs of MHC-matched animals. FINDINGS: In MHC-matched animals, there was considerable heterogeneity in the specificity and magnitude of T cell responses detected via individual peptide gamma interferon (IFN-γ) enzyme-linked immunospot (ELISPOT) assays. These findings were further supported by full proteome pooled peptide matrix ELISPOT data collected from this cohort at 52 weeks post-infection. Interestingly, peptide regions that elicited dominant T cell responses were more commonly shared between MHC-matched MCM than peptide regions that elicited non-dominant T cell responses. CONCLUSIONS: Our findings suggest that, while some T cell responses mounted during chronic infection by MHC-matched MCM are similar, the majority of responses are highly variable. Shared responses detected in this study between MHC-matched MCM were directed against epitopes that had previously elicited relatively dominant responses in MCM with the same MHC class I haplotype, suggesting that the factors that influence dominance may influence the reproducibility of responses as well. This may be an important consideration for future T cell-based vaccines aiming to consistently and reproducibly elicit protective T cell responses.

Specific CD8+ T cell responses correlate with control of simian immunodeficiency virus replication in Mauritian cynomolgus macaques.

Specific major histocompatibility complex (MHC) class I alleles are associated with an increased frequency of spontaneous control of human and simian immunodeficiency viruses (HIV and SIV). The mechanism of control is thought to involve MHC class I-restricted CD8(+) T cells, but it is not clear whether particular CD8(+) T cell responses or a broad repertoire of epitope-specific CD8(+) T cell populations (termed T cell breadth) are principally responsible for mediating immunologic control. To test the hypothesis that heterozygous macaques control SIV replication as a function of superior T cell breadth, we infected MHC-homozygous and MHC-heterozygous cynomolgus macaques with the pathogenic virus SIVmac239. As measured by a gamma interferon enzyme-linked immunosorbent spot assay (IFN-γ ELISPOT) using blood, T cell breadth did not differ significantly between homozygotes and heterozygotes. Surprisingly, macaques that controlled SIV replication, regardless of their MHC zygosity, shared durable T cell responses against similar regions of Nef. While the limited genetic variability in these animals prevents us from making generalizations about the importance of Nef-specific T cell responses in controlling HIV, these results suggest that the T cell-mediated control of virus replication that we observed is more likely the consequence of targeting specificity rather than T cell breadth.