Photoacoustic imaging for non-invasive assessment of biomarkers of intestinal injury in experimental necrotizing enterocolitis.

BACKGROUND: Necrotizing enterocolitis (NEC) is an often-lethal disease of the premature infant intestinal tract, exacerbated by significant diagnostic difficulties. In NEC, the intestine exhibits hypoperfusion and dysmotility, contributing to disease pathogenesis. However, these features cannot be accurately and quantitively assessed with current imaging modalities. We have previously demonstrated the ability of photoacoustic imaging (PAI) to non-invasively assess intestinal tissue oxygenation and motility in a healthy neonatal rat model. METHODS: In this first-in-disease application, we evaluated NEC using PAI to assess intestinal health biomarkers in an experimental model of NEC. NEC was induced in neonatal rats from birth to 4-days. Healthy breastfed (BF) and NEC rat pups were imaged at 2- and 4-days. RESULTS: Intestinal tissue oxygen saturation was measured with PAI, and NEC pups showed significant decreases at 2- and 4-days. Ultrasound and PAI cine recordings were used to capture intestinal peristalsis and contrast agent transit within the intestine. Intestinal motility, assessed using computational intestinal deformation analysis, demonstrated significant reductions in both early and established NEC. NEC damage was confirmed with histology and dysmotility was confirmed by small intestinal transit assay. CONCLUSION: This preclinical study presents PAI as an emerging diagnostic imaging modality for intestinal disease assessment in premature infants. IMPACT: Necrotizing enterocolitis (NEC) is a devastating intestinal disease affecting premature infants with significant mortality. NEC presents significant clinical diagnostic difficulties, with limited diagnostic confidence complicating timely and effective interventional efforts. This study is an important foundational first-in-disease preclinical study that establishes the utility for PAI to detect changes in intestinal tissue oxygenation and intestinal motility with NEC disease induction and progression. This study demonstrates the feasibility and exceptional promise for the use of PAI to non-invasively assess oxygenation and motility in the healthy and diseased infant intestine.

The Effect of 4-Factor Prothrombin Complex Concentrate to Reverse Factor Xa Inhibitors in Patients With Traumatic Intracranial Hemorrhage.

The utility of 4-factor prothrombin complex concentrate (4F-PCC) for reversal in patients on factor Xa inhibitors (XaI) is unclear, specifically in mild traumatic brain injury (mTBI). This is a retrospective review over 6 years at a level 1 trauma center of patients presenting with mTBI on XaI comparing outcomes for those that received 4F-PCC to those that did not. 140 patients were included, 103 (74%) of these patients received 4F-PCC while 37 (26%) did not. There was no significant difference in neurologic decline within 48 hours of admission or need for neurosurgical intervention. Interestingly, there was no difference in ICH progression (16% vs 14%, P = .77). In this study, 4F-PCC given after mild traumatic brain injury did not impact ICH progression, neurologic decline, or need for neurosurgical intervention. Although limited in numbers, this study suggests that 4F-PCC is not necessarily required in mTBI and further studies are indicated.

Contemporary Management and Outcomes of Blunt Traumatic AAST-OIS Grade III and IV Pancreatic Injuries in Children: A TQIP analysis.

BACKGROUND: The Trauma Quality Improvement Program (TQIP) database has delineated management strategies and outcomes for adults with AAST-OIS grade III-IV pancreatic injuries and suggests that non-operative management (NOM) is a viable option for these injuries. However, management strategies vary for children following significant pancreatic injuries and outcomes for these intermediate/high grade injuries have not been sufficiently studied. Our aim is to describe the management and outcomes for grade III-IV pancreatic injuries utilizing TQIP. We hypothesize that pediatric patients with intermediate/high grade injuries can be safely managed with NOM. METHODS: All pediatric patients (<18 years old) registered in TQIP between 2013-2021 who suffered a grade III or IV pancreatic injury due to blunt trauma were included in the current study. Patient demographics, clinical characteristics, complications, and in-hospital mortality were compared between the different treatment strategies for pancreatic injury: NOM versus drainage and/or pancreatic resection. RESULTS: 580 patients meeting criteria were identified. A total of 416 pediatric patients suffered a grade III pancreatic injury; 79% (N = 332) were NOM, 7% (N = 27) received a drain, and 14% (N = 57) underwent a pancreatic resection. A further 164 patients suffered a grade IV pancreatic injury; 77% (N = 126) were NOM, 11% (N = 18) received a drain, and 12% (N = 20) underwent a pancreatic resection. No differences in overall injury severity or demographical data were observed between the treatment groups. No difference in in-hospital mortality was detected between the different management strategies. Patients who received a drain had a longer hospital length of stay (LOS). CONCLUSION: The majority of children with AAST-OIS grade III-IV pancreatic injuries are managed nonoperatively. NOM is a reasonable strategy for these injuries and results in equivalent in-hospital adverse outcome profiles as pancreatic drainage or resection with a shorter hospital LOS. LEVEL OF EVIDENCE: Level III.

Does the Timing of Surgical Intervention Impact Outcomes in Necrotizing Enterocolitis?

OBJECTIVES: The optimal time for intervention in surgical necrotizing enterocolitis (sNEC) remains to be elucidated. Surgical management varies between peritoneal drain (PD), laparotomy (LAP), and PD with subsequent LAP (PD + LAP). We propose that some infants with surgical NEC benefit from late (>48 h) operative intervention to allow for resuscitation. METHODS: A retrospective comparison of clinical information in infants with sNEC from 2012 to 2022 was performed. Early intervention was defined as less than 48 hours from time of NEC diagnosis to surgical intervention. RESULTS: 118 infants were identified, 92 underwent early intervention (62 LAP; 22 PD; 8 PD + LAP) and 26 underwent late intervention (20 LAP; 2 PD; 4 PD + LAP). Infants with early intervention were diagnosed younger (DOL 8 [6, 15] vs 20 [11, 26]; P=< .05) with more pneumoperitoneum (76% vs 23%; P=< .05). The early intervention group had a higher mortality (35% vs 15%; P=< .05). When excluding infants with pneumoperitoneum, the early intervention group had a higher mortality rate (10/22 (45%), 4/26 (15%); P < .05) and had more bowel resected (29 ± 17 cm vs 9 ± 8 cm; P < .05), with the same number of patients scoring above 3 on the MD7 criteria. CONCLUSION: Infants with NEC who underwent early surgical intervention had a higher mortality and more bowel resected. While this study has a provocative finding, it is severely limited by the non-specific 48-hour cut off. However, our data suggests that a period of medical optimization may improve outcomes in infants with sNEC and thus more in-depth studies are needed.

A Comparative Analysis of "Surgery First" vs. "Endoscopy First" for Pediatric Choledocholithiasis Presenting at the End of the Week.

BACKGROUND: Choledocholithiasis in children is commonly managed with an "endoscopy first" (EF) strategy (endoscopic retrograde cholangiopancreatography (ERCP) followed by laparoscopic cholecystectomy (LC) under a separate anesthetic). Endoscopic Retrograde Cholangiopancreatography is limited at the end of the week (EoW). We hypothesize that a "surgery first" (SF) approach with LC, intraoperative cholangiogram (IOC), and possible laparoscopic common bile duct exploration (LCBDE) can decrease length of stay (LOS) and time to definitive intervention (TTDI). METHODS: This is a retrospective single-center cohort study conducted between 2018 and 2023 in pediatric patients with suspected choledocholithiasis. Work week (WW) presentation included admission between Monday and Thursday. Time to definitive intervention was defined as time to LC. RESULTS: 88 pediatric patients were identified, 61 managed with SF (33 WW and 28 EoW) and 27 managed with EF (18 WW and 9 EoW). Both SF groups had shorter mean LOS for WW and EoW presentation (64.5 h, 92.4 h, 112.9 h, and 113.0 h; P < .05). There was a downtreading TTDI in the SF groups (SF: WW 24.7 h and EoW 21.7 h; EF: WW 31.7 h and EoW 35.9 h; P = .11). 44 patients underwent LCBDE with similar success rates (91.6% WW and 85% EoW; P = 1.0). All EF patients received 2 procedures; 69% of SF patients were definitively managed with one. CONCLUSION: Children with choledocholithiasis at the EoW have a longer LOS and TTDI. These findings are amplified when children enter an EF treatment pathway. An SF approach results in shorter LOS with fewer procedures, regardless of the time of presentation.

A Novel Taxonomy of Intraoperative Cholangiograms in Suspected Choledocholithiasis: A Tool for Advancing Laparoscopic Common Bile Duct Exploration Outcomes Research.

BACKGROUND: Cholangiography for visualization of the biliary tree during laparoscopic cholecystectomy is an important diagnostic roadmap in the context of suspected choledocholithiasis (CDL). The renewed interest in transcystic laparoscopic common bile duct exploration (LCBDE) necessitates a general description of the range of CDL presentations. Our aim was to establish a novel classification system of intraoperative cholangiograms (IOCs) to advance research efforts in this field. METHODS: A novel cholangiogram classification system, featuring 8 distinct presentations of choledocholithiasis, was applied to a data set of 80 preintervention IOCs for suspected choledocholithiasis. The classification system is as follows: A (no common bile duct stones, duodenal filling present, and concern for air bubbles), B (no common bile duct stones, no duodenal filling, and concern for sludge), C1 (stone(s) < 2x size of cystic duct with duodenal filling), C2 (stone(s) < 2x size of cystic duct without duodenal filling), D1 (stone(s) ≥ 2x size of cystic duct with duodenal filling), D2 (stone(s) ≥ 2x size of cystic duct without duodenal filling), E1 (congenital anatomical variant and/or common duct stricture), and E2 (surgically altered biliary anatomy). RESULTS: Cholangiogram review yielded preintervention classifications for 6 of 8 variants (A-E): A (7.5%), B (3.75%), C1 (23.75%), C2 (42.5%), D1 (15%), and D2 (7.5%). Analysis of cystic duct diameter yielded no significant differences among classification groups, indicating no predominant pattern of cystic duct anatomy within a given classification. DISCUSSION: An IOC classification system for suspected choledocholithiasis is foundational to answering key clinical questions for transcystic laparoscopic common bile duct exploration.