Real-world evidence on adjuvant chemotherapy in older adults with stage II/III colon cancer

Colon cancer represents one of the most common cancers diagnosed in older adults worldwide. The standard of care in resected stage II and stage III colon cancer continues to evolve. While there is unequivocal evidence to suggest both disease free and overall survival benefits with the use of combination chemotherapy in patients with stage III colon cancer, data regarding its use in patients with stage II colon cancer are less clear. Further, although colon cancer is a disease that affects older adults, there is considerable debate on the value of adjuvant chemotherapy in the aging population. In particular, many older patients are undertreated when compared to their younger counterparts. In this review, we will describe the clinical trials that contributed to the current adjuvant chemotherapy approach in colon cancer, discuss representation of older adults in trials and the specific challenges associated with the management of this sub-population, and highlight the role of comprehensive geriatric assessments. We will also review how real-world evidence complements the data gaps from clinical trials of early stage colon cancer.     

Heterograft biocompatibility without proteolytic digestion

Bovine and sheep carotid heterografts (BED and S-ED) were modified by sequential treatment with 95% ethanol and 1.3% dialdehyde starch and stored in 70% ethanol. Compared with ficin digested, dialdehyde tanned bovine carotid artery (B-FD), chemical treatment produced heterografts with greater in vitro anastomotic tensile strength and significantly reduced surface clotting time. Seven of 20 canine inferior caval implants of B-ED heterografts remained patent for periods up to 4 weeks while 4 of 5 B-FD interpositions thrombosed within 2 hr. A patency rate of over 90% was obtained in canine abdominal and thoracic aorta B-ED and S-ED interpositions during a follow up period of 3 to 6 months. As arteriovenous fistulas B-ED heterografts maintained excellent patency, tolerated repetitive percutaneous puncture and exhibited self sealing capability. Microscopic examination of longterm B-ED implants showed smooth intimal surfaces with no fibrin deposition or morphologic evidence of rejection. In contrast to the ficin digested heterograft, ethanol-dialdehyde processing suppresses antigenic potential but preserves structural integrity. The end product retains components of the heterograft wall and results in a nonviable, biocompatible conduit with improved thromboresistance and greater strength.     

Acquired immune deficiency syndrome and systemic lupus erythematosis: potential causes of surgical emergencies of the hand

Compartment Syndrome (CS) is a disease that has 2 etiologies, that of acute events and that of chronic. It occurs when the pressure in a fascia-encased compartment exceeds the profusion pressure in tissue. The end result, when left untreated, is muscle and nerve ischemia that can cause significant morbidity. Nerve paralysis, muscle necrosis and fibrosis and, when occurring in an extremity, loss of the limb are some of the potential outcomes of missed diagnosis. This case series involves 2 cases of CS that where caused by vasculitis with etiologies of human immunodeficiency virus and systemic lupus erythematosis. Autoimmune vasculitis has many systemic and local manifestations, but to our knowledge CS has not been described as one of its sequelae. The following is literature review and presentation of these 2 cases.     

Donor-specific indirect pathway analysis reveals a B-cell-independent signature which reflects outcomes in kidney transplant recipients

To investigate the role of donor‐specific indirect pathway T cells in renal transplant tolerance, we analyzed responses in peripheral blood of 45 patients using the trans‐vivo delayed‐type hypersensitivity assay. Subjects were enrolled into five groups—identical twin, clinically tolerant (TOL), steroid monotherapy (MONO), standard immunosuppression (SI) and chronic rejection (CR)—based on transplant type, posttransplant immunosuppression and graft function. The indirect pathway was active in all groups except twins but distinct intergroup differences were evident, corresponding to clinical status. The antidonor indirect pathway T effector response increased across patient groups (TOL < MONO < SI < CR; p < 0.0001) whereas antidonor indirect pathway T regulatory response decreased (TOL > MONO = SI > CR; p < 0.005). This pattern differed from that seen in circulating naïve B‐cell numbers and in a cross‐platform biomarker analysis, where patients on monotherapy were not ranked closest to TOL patients, but rather were indistinguishable from chronically rejecting patients. Cross‐sectional analysis of the indirect pathway revealed a spectrum in T‐regulatory:T‐effector balance, ranging from TOL patients having predominantly regulatory responses to CR patients having predominantly effector responses. Therefore, the indirect pathway measurements reflect a distinct aspect of tolerance from the recently reported elevation of circulating naïve B cells, which was apparent only in recipients off immunosuppression.     

Perinatal Immunization With Vaccine-Grade Listeria monocytogenes Provides Protection Against Murine Th2 Airway Inflammation

Purpose

Asthma is a chronic respiratory disorder that leads to inflammation and narrowing of the airways. Its global prevalence has attained epidemic levels and treatment options that reach beyond temporary relief of symptoms are urgently needed. Since the processes leading to clinically symptomatic asthma start early in life, we set out to systematically evaluate a neonatal immunotherapeutic based on Listeria monocytogenes (Lm) for the control of allergic sensitization.

Methods

We modified Lm to express the model allergen, ovalbumin (OVA), and tested the ability of neonatal immunization with this strain to control allergic sensitization in a mouse model of OVA-induced asthma. Mice were immunized as newborns with live or heat killed LmOVA or live Lm, followed 6 weeks later by allergic sensitization with OVA. In order to determine whether the T_H1-polarizing effect of this vaccine vector inadvertently may exacerbate development of certain T_H1-driven allergic diseases, mice immunized as newborns were assessed in a model of adult hypersensitivity pneumonitis (HP).

Results

Both LmOVA and Lm-control vaccines were highly effective in providing long-lasting protection from airway inflammation after only one immunization given perinatally. Serum antibody levels and lung cytokine production suggest that this prophylactic strategy is associated with an allergen specific T_H1-dominated response. Specifically, LmOVA vaccinated mice displayed significantly elevated OVA-specific serum IgG2a, but no difference in anti-OVA IgE antibodies and only slightly decreased anti-OVA IgG1 antibodies. Importantly, Lm-based neonatal vaccination did not exacerbate Th1/Th17 driven HP, arguing against broad spectrum immune skewing.

Conclusions

Our findings highlight the promise of early life Lm-based immunomodulatory interventions as a prophylactic strategy for allergic asthma.     

Applying Machine Learning Across Sites: External Validation of a Surgical Site Infection Detection Algorithm

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Discordant Cardiopulmonary Resuscitation and Code Status at Death

ContextOne fundamental way to honor patient autonomy is to establish and enact their wishes for end-of-life care. Limited research exists regarding adherence with code status.ObjectivesThis study aimed to characterize cardiopulmonary resuscitation (CPR) attempts discordant with documented code status at the time of death in the U.S. and to elucidate potential contributing factors.MethodsThe Cerner Acute Physiology and Chronic Health Evaluation (APACHE) outcomes database, which includes 237 U.S. hospitals that collect manually abstracted data from all critical care patients, was queried for adults admitted to intensive care units with a documented code status at the time of death from January 2008 to December 2016. The primary outcome was discordant CPR at death. Multivariable logistic regression models were used to identify patient-level and hospital-level associated factors after adjustment for age, hospital, and illness severity (APACHE III score).ResultsA total of 21,537 patients from 56 hospitals were included. Of patients with a do-not-resuscitate code status, 149 (0.8%) received CPR at death, and associated factors included black race, higher APACHE III score, or treatment in small or nonteaching hospitals. Of patients with a full code status, 203 (9.0%) did not receive CPR at death, and associated factors included higher APACHE III score, primary neurologic or trauma diagnosis, or admission in a more recent year.ConclusionAt the time of death, 1.6% of patients received or did not undergo CPR in a manner discordant with their documented code statuses. Race and institutional factors were associated with discordant resuscitation, and addressing these disparities may promote concordant end-of-life care in all patients.     

Spontaneous Intercostal Lung Hernia

Spontaneous intercostal lung herniae are infrequently described. Presented is a patient whose hernia arose after a vigorous cough. Treatment consisted of excision of the sac and repair. Demonstration of the defect roentgenographically and on physical examination is diagnostic. The defect can regress spontaneously; surgery is frequently curative, although techniques vary.