Subcutaneous checkpoint inhibition is equivalent to systemic delivery when combined with nelitolimod delivered via pressure-enabled drug delivery for depletion of intrahepatic myeloid-derived suppressor cells and control of liver metastases.

BACKGROUND: Toll-like receptor 9 (TLR9) agonists induce inflammatory responses that promote the killing of infectious micro-organisms, cancer cells and develop adaptive immune responses. Their ability as immunomodulators to enhance the activity of checkpoint inhibitors (CPI) in treating liver tumors is limited in part by the distinctive biology of intrahepatic myeloid-derived suppressor cells (MDSC) and challenges with tumor-specific therapeutic delivery. We have shown that the regional delivery of type C TLR9 agonist via pressure-enabled drug delivery (PEDD) system improves delivery to the tumor, enhances depletion of MDSCs and overall, stimulates the immune system in combination with or without CPI. Currently, CPIs are delivered intravenously, although there is a growing interest in its subcutaneous (SQ) administration. We compared nelitolimod formerly known as SD-101 administered using PEDD in combination with systemic (Sys) or SQ CPI in murine liver metastases (LM). METHODS: The LM model was developed by injecting MC38-Luc cells via the spleen of 8-12 week old male C57/BL6 mice followed by splenectomy. After a week, fluorescently labeled nelitolimod (10 µg/mouse) was delivered via PEDD and co-administered anti-programmed cell death-1 (α-PD-1) either via Sys or SQ. Tumor burden was monitored by in vivo imaging system. Serum cytokine levels were analyzed by Luminex. Tissues were harvested on Day 3 (D3) or Day 10 (D10) post-PEDD to enrich CD45+ cells and were analyzed via NanoString targeted transcriptomics (D3) or flow cytometry (FC, D10) to interrogate immune cell populations (D10). For NanoString analysis, the innate immune panels were selected, and for FC, MDSCs (CD11b+Gr1+), B cells (B220+), dendritic cells (DC, CD11c+), T (CD3+) cells, and M1-like macrophages (F4/80+CD38+Egr2-) were quantified. RESULTS: Nelitolimod delivered via PEDD resulted in changes in innate and adaptive immune cells within LM, including depletion of liver MDSC and increased M1-like macrophages in the liver, which are supportive of antitumor immunity. While CPI monotherapy failed to control tumor progression, nelitolimod and CPI combination improved LM control, survival and antitumor immunity beyond the nelitolimod monotherapy effect, irrespective of CPI delivery route. CONCLUSION: The SQ route of CPI delivery was equivalent to Sys in combination with nelitolimod, suggesting SQ-CPI may be a rational choice in combination with PEDD of nelitolimod for liver tumor treatment.

Interpectoral nerve blocks may lower postoperative narcotic use after mastectomy.

BACKGROUND: Pain management following mastectomy is a significant challenge often requiring opioids. Nonopioid pain management utilizing nerve blocks has been shown in other fields to reduce postoperative opioid use and may be effective for postoperative pain in mastectomy patients. The primary purpose of this study was to compare postoperative opioid use, measured in morphine milligram equivalents (MME), between mastectomy patients who underwent interpectoral nerve block (IPNB) and a historical control group. Secondary outcomes included length of stay (LOS) and postoperative pain scores. METHODS: This is a single-center, retrospective cohort study. The charts of women who underwent mastectomy for cancer without immediate reconstruction from 10/2017-12/2019 were reviewed. Wilcoxon rank sum test was used for unadjusted analysis and multiple linear regression for adjusted analysis. RESULTS: There were 105 patients included in this study, of which 37 (35%) underwent IPNB. In unadjusted analysis, median MME use was significantly lower in patients that received IPNB compared to the control group (IPNB = 5, controls = 17, p = 0.03). Patients that received IPNB had an observed reduction in LOS and postoperative pain, though these results failed to reach statistical significance. There were no IPNB-related complications. CONCLUSIONS: IPNB may be an effective strategy to decrease postoperative opioid use in mastectomy patients. Larger, prospective studies are needed to further investigate the effectiveness of IPNB.

Management of Acute Appendicitis in HIV/AIDs Patients: A 19-year Review from the National In-Patient Sample.

BACKGROUND: Acute Appendicitis (AA), one of the most common surgical emergencies, is usually managed operatively. There is a paucity of data addressing how HIV/AIDS affects management of acute uncomplicated appendicitis. METHODS: A retrospective review of HIV/AIDS positive (HPos) versus negative (HNeg) patients with acute, uncomplicated appendicitis over a 19-year period. The primary outcome was undergoing appendectomy. RESULTS: Among 912,779 AA patients, 4,291 patients were HPos. HIV rates increased from 3.8/1,000 in 2000 to 6.3 per 1,000 appendicitis cases in 2019 (p<0.001). HPos patients were older, less likely to have private insurance, and more likely to have psychiatric illnesses, hypertension, and a history of prior malignancy. HPos AA patients underwent operative intervention less often than HNeg AA patients (90.7% versus 97.7%;p<0.001). Overall, comparing HPos to HNeg patients, there was no difference in post-operative infections or mortality. CONCLUSION: HIV-positive status should not deter surgeons from offering definitive care for acute uncomplicated appendicitis.

Hospitalizations for pediatric dog bite injuries in the United States.

BACKGROUND: Dog bites are a common cause of pediatric trauma requiring hospital admission. We aim to describe pediatric bite victims, associated injuries and interventions. METHODS: Children (≤18 years old) were identified with an ICD-9 diagnosis of dog bite in the Kids' Inpatient Database for the years 2006, 2009 and 2012. National estimates were obtained using case weighting. Multivariable logistic regression was performed. RESULTS: We identified 6323 admissions for a dog bite with mean age of 6.63 years. Patients were predominately male (56.9%), non-Hispanic white (61.9%), resided in the South (35.1%), and in an urban environment (59.9%). Almost one third underwent a surgical procedure. Open wounds of the head, neck and trunk were the most common injury and decreased in prevalence with increasing age. Open wounds of the extremities were the second most common and the prevalence increased with increasing age. Children aged 1-4 and 5-10 years were both more than three times more likely to be admitted than those more than age 11. CONCLUSIONS: Dog bite injuries are common for pediatric patients. Children less than age 11 are at greatest risk, particularly in the summer. Dog safety training should be focused on elementary and middle school children close to the start of summer vacation. LEVEL OF EVIDENCE: III.

Acute Alcohol Use and Injury Patterns in Young Adult Prehospital Patients.

The objective was to determine if acute alcohol consumption is associated with differences in injury pattern among young adult patients with traumatic injuries presenting to emergency medical services (EMS). A cross-sectional, retrospective review of prehospital patient care reports (PCRs) was conducted evaluating injured patients who presented to a collegiate EMS agency from January 1, 2011 to December 31, 2012. Included patients were age 18-24 y and sustained an injury within the previous 24 h. PCRs were reviewed independently by two abstractors to determine if the patient was documented to have acutely consumed alcohol proximate to his/her injury. Primary and secondary sites of regional body injury were recorded. Injury severity was recorded using the Revised Trauma Score (RTS). The association between primary injury site and acute alcohol use was assessed using a chi-square test. Multiple logistic regression was used to control for sex in predicting injury type. Of 440 injured patients, 135 (30.6%) had documented alcohol use prior to injury. Acute alcohol consumption altered the overall pattern of regional injury (p < 0.001). Alcohol users were more likely to present with injury secondary to assault, fall/trip, and unknown mechanism of injury (p < 0.001, all comparisons). RTS scores were statistically lower in the alcohol group (p < 0.001), although the clinical significance of this is unclear. Controlling for sex, acute alcohol consumption predicted increased risk of head/neck injury 5.59-fold (p < 0.001). Acute alcohol use in collegiate EMS patients appears to alter injury patterns in young adults and increases risk of head/neck injury. EMS providers in similar agencies should consider these trends when assessing and treating injured college-aged patients.