Impact of Tumor Size and Management on Survival in Small Gastric Gastrointestinal Stromal Tumors.

BACKGROUND: Society guidelines remain inconsistent on the role of endoscopic and radiographic surveillance as an alternative to surgical resection of small gastric gastrointestinal stromal tumors (GISTs). Herein, we aimed to assess survival among patients with gastric GISTs undergoing observation versus surgical resection, stratified by tumor size. METHODS: The National Cancer Database (NCDB) was queried for gastric GISTs < 2 cm diagnosed from 2010-2017. Patients were stratified by management strategy-observation vs surgical resection. The primary outcome, overall survival (OS), was examined with Kaplan-Meier and multivariable Cox proportional hazard methods. Subgroup analyses were conducted on tumors < 1 cm and 1-2 cm in size. RESULTS: Altogether, 1208 patients were identified: 439 (36.3%) undergoing observation and 769 (63.7%) receiving surgical resection. In the overall cohort, patients undergoing surgical resection demonstrated improved survival (93.6 vs. 88.8% 5-year OS, p=0.02). In multivariable analysis, upfront surgical resection was not associated with a reduction in mortality; however, there was a significant interaction with tumor size. For patients with tumors < 1 cm, there was no difference in survival based on management strategy. However, resection of tumors 1-2 cm was associated with improved survival relative to surveillance. CONCLUSIONS: While surgical resection and surveillance were associated with similar survival for patients with gastric GISTs < 1 cm, this NCDB analysis suggests that patients with tumor size ≥ 1 cm may benefit from upfront surgical resection. Prospective studies comparing these two approaches and their impact on recurrence-free and disease-specific survival are needed to better align consensus guidelines and recommendations.

Complement-targeting therapeutics for ischemia-reperfusion injury in transplantation and the potential for ex vivo delivery.

Organ shortages and an expanding waitlist have led to increased utilization of marginal organs. All donor organs are subject to varying degrees of IRI during the transplant process. Extended criteria organs, including those from older donors and organs donated after circulatory death are especially vulnerable to ischemia-reperfusion injury (IRI). Involvement of the complement cascade in mediating IRI has been studied extensively. Complement plays a vital role in the propagation of IRI and subsequent recruitment of the adaptive immune elements. Complement inhibition at various points of the pathway has been shown to mitigate IRI and minimize future immune-mediated injury in preclinical models. The recent introduction of ex vivo machine perfusion platforms provides an ideal window for therapeutic interventions. Here we review the role of complement in IRI by organ system and highlight potential therapeutic targets for intervention during ex vivo machine preservation of donor organs.

Gene Therapy: Will the Promise of Optimizing Lung Allografts Become Reality?

Lung transplantation is the definitive therapy for patients living with end-stage lung disease. Despite significant progress made in the field, graft survival remains the lowest of all solid organ transplants. Additionally, the lung has among the lowest of organ utilization rates-among eligible donors, only 22% of lungs from multi-organ donors were transplanted in 2019. Novel strategies are needed to rehabilitate marginal organs and improve graft survival. Gene therapy is one promising strategy in optimizing donor allografts. Over-expression or inhibition of specific genes can be achieved to target various pathways of graft injury, including ischemic-reperfusion injuries, humoral or cellular rejection, and chronic lung allograft dysfunction. Experiments in animal models have historically utilized adenovirus-based vectors and the majority of literature in lung transplantation has focused on overexpression of IL-10. Although several strategies were shown to prevent rejection and prolong graft survival in preclinical models, none have led to clinical translation. The past decade has seen a renaissance in the field of gene therapy and two AAV-based in vivo gene therapies are now FDA-approved for clinical use. Concurrently, normothermic ex vivo machine perfusion technology has emerged as an alternative to traditional static cold storage. This preservation method keeps organs physiologically active during storage and thus potentially offers a platform for gene therapy. This review will explore the advantages and disadvantages of various gene therapy modalities, review various candidate genes implicated in various stages of allograft injury and summarize the recent efforts in optimizing donor lungs using gene therapy.

Harnessing the B Cell Response in Kidney Transplantation - Current State and Future Directions.

Despite dramatic improvement in kidney transplantation outcomes over the last decades due to advent of modern immunosuppressive agents, long-term outcomes remain poor. Antibody-mediated rejection (ABMR), a B cell driven process, accounts for the majority of chronic graft failures. There are currently no FDA-approved regimens for ABMR; however, several clinical trials are currently on-going. In this review, we present current mechanisms of B cell response in kidney transplantation, the clinical impact of sensitization and ABMR, the B cell response under current immunosuppressive regimens, and ongoing clinical trials for ABMR and desensitization treatment.

Regional anesthesia does not decrease inpatient or outpatient opioid demand in distal femur fracture surgery.

INTRODUCTION: Regional anesthesia (RA) is sometimes used to decrease pain and opioid consumption in distal femur fractures. However, the real-world impact of RA on inpatient opioid consumption and outpatient opioid demand is not well known. The hypothesis of this study is that RA would be associated with decreased inpatient opioid consumption and outpatient opioid demand. METHODS: This study evaluated inpatient post-operative opioid consumption (0-24 h, 24-48 h, 48-72 h) and outpatient opioid demand (discharge to 2 weeks, 6 weeks, and 90 days) in all patients ages 18 and older undergoing operative treatment of distal femur fractures at a single institution from 7/2013 to 7/2018 (n = 230). Unadjusted and adjusted multivariable models were used to evaluate the impact of RA and other baseline patient and operative characteristics on inpatient opioid consumption and outpatient opioid demand. RESULTS: Adjusted models demonstrated a small, significant increase in inpatient opioid consumption in patients with RA compared to no RA (4.7 estimated OE's without RA vs 6.2 OE's with RA from 24- to 48-h post-op, p < 0.05) but otherwise no significant differences at other timepoints (6.7 estimated OE's without RA vs 6.9 OE's with RA from 0- to 24-h post-op and 4.5 vs 4.4 from 48- to 72-h post-op, p > 0.05). Estimated cumulative outpatient opioid demand was significantly higher in patients with RA from discharge to 6 weeks and to 90 days (55.8 OE's without RA vs 63.9 with RA from discharge to 2 weeks, p > 0.05; 74.9 vs 95.1 OE's to 6 weeks, and 85 vs 113.1 OE's to 90 days, p < 0.05). DISCUSSION: In distal femur fracture surgery, RA was associated with increased inpatient and outpatient opioid demand after adjusting for baseline patient and treatment characteristics. These results call into question the routine use of RA in distal femur fractures. LEVEL OF EVIDENCE: Level III, retrospective, therapeutic cohort study.

Regional anesthesia does not decrease inpatient or outpatient opioid demand in femoral shaft fracture surgery.

INTRODUCTION: Regional anesthesia (RA) may be used in femoral shaft fracture surgery to decrease pain and opioid consumption. However, the impact of RA on inpatient and outpatient opioid demand in patients undergoing femoral shaft fracture surgery is largely unknown. The aim of this study was to evaluate the impact of RA on inpatient opioid consumption and outpatient opioid demand in patients undergoing femoral shaft fracture surgery. METHODS: Inpatient opioid consumption and outpatient opioid demand in all patients undergoing femoral shaft fracture surgery was recorded at a single, Level I trauma center from 7/2013 - 7/2018 (n=436). In addition to RA, baseline and treatment factors including age, sex, race, body mass index (BMI), smoking, chronic opioid use, American Society of Anesthesiologists (ASA) score, injury mechanism, additional injuries, open injury, and additional inpatient surgery were recorded. Unadjusted and adjusted multivariable models were used to evaluate the impact of RA on inpatient opioid consumption and outpatient opioid demand. RESULTS: Adjusted models demonstrated increases in inpatient opioid consumption in patients with RA (6.9 estimated OE's without RA vs 8.8 OE's with RA from 48-72 hours post-op, p<0.05) but no significant differences at other timepoints (10.3 estimated OE's without RA vs 9.2 OE's with RA from 0-24 hours post-op, 8.2 vs 8.8 from 24-48 hours post-op, p>0.05). Estimated cumulative outpatient opioid demand did not differ significantly in patients with RA (82.3 OE's without RA vs 94.8 with RA from discharge to two-weeks, 105.4 vs 116.3 OE's to 6-weeks, and 124.5 vs 137.9 OE's to 90-days, all p>0.05). Late opioid refills were significantly more common in patients with RA (1.57 odds at 2-weeks to 6-weeks, 1.69 odds at 6-weeks to 90-days, p<0.05) DISCUSSION: In femoral shaft fracture surgery, RA was not associated with decreased opioid demand after adjusting for baseline patient and treatment characteristics. These results provide a real-world estimate of the impact of RA on opioid demand in femoral shaft fracture surgery and encourage providers to seek alternative analgesic modalities. LEVEL OF EVIDENCE: Level III, retrospective, therapeutic cohort study.

Legislation Only Limiting Opioid Prescription Length Has Minimal Impact on Prescribing in Orthopaedic Trauma.

This study evaluates the efficacy of North Carolina's Strengthen Opioid Misuse Prevention (STOP) Act in reducing the volume and rate of 90-day perioperative opioid prescribing to patients ages 18 and older after orthopaedic trauma surgery. Patients undergoing fracture surgery from January 2017 to June 2017 (pre-STOP) were compared with patients undergoing fracture surgery from January 2018 to June 2018 (post-STOP). Adjusted analyses demonstrated that patients undergoing surgery after the STOP Act (n = 730) were prescribed significantly lower volume of opioids in the discharge to 2-week time frame and at the first postoperative prescription (7.3 and 5.8 fewer oxycodone, respectively). Otherwise, there were no significant differences between the two cohorts in adjusted volume or rates of 90-day opioid prescribing. The STOP act has had only a minor impact on early post-discharge opioid prescribing in patients undergoing fracture surgery. These findings question the efficacy of this type of legislation in combating opioid overprescribing in orthopaedic trauma. (Journal of Surgical Orthopaedic Advances 30(2):101-107, 2021).