CD24-Fc suppression of immune related adverse events in a therapeutic cancer vaccine model of murine neuroblastoma.

Introduction: The combination of Myc-suppressed whole tumor cells with checkpoint inhibitors targeting CTLA-4 and PD-L1 generates a potent therapeutic cancer vaccine in a mouse neuroblastoma model. As immunotherapies translate from pre-clinical to clinical trials, the potential immune-related adverse events (irAEs) associated with induction of potent immunity must be addressed. The CD24-Siglec 10/G interaction is an innate checkpoint that abrogates inflammatory responses to molecules released by damaged cells, but its role in cancer immunology is not well defined. We investigate irAEs of an effective whole cell neuroblastoma vaccine and subsequently the effect of CD24-Fc, a CD24 and Fc fusion protein, on both the vaccine efficacy and induced irAEs in a mouse neuroblastoma model. Methods: To test whether the whole tumor cell vaccination leads to autoimmune responses in other organ systems we harvested lung, heart, kidney and colon from naïve mice (n=3), unvaccinated tumor only mice (n=3), and vaccinated mice with CD24 Fc (n=12) or human IgG-Fc control (n=12) after tumor inoculation and vaccination therapy at day 30. The Immune cell infiltrates and immunogenic pathway signatures in different organ systems were investigated using NanoString Autoimmune Profiling arrays. Nanostring RNA transcript results were validated with immunohistochemistry staining. Results: The whole tumor cell vaccine combined with immune checkpoint therapy triggers occult organ specific immune cell infiltrates, primarily in cardiac tissue and to a lesser extent in the renal and lung tissue, but not in the colon. CD24-Fc administration with vaccination partially impedes anti-tumor immunity but delaying CD24-Fc administration after initial vaccination reverses this effect. CD24-Fc treatment also ameliorates the autoimmune response induced by effective tumor vaccination in the heart. Discussion: This study illustrates that the combination of Myc suppressed whole tumor cell vaccination with checkpoint inhibitors is an effective therapy, but occult immune infiltrates are induced in several organ systems in a mouse neuroblastoma model. The systemic administration of CD24-Fc suppresses autoimmune tissue responses, but appropriate timing of administration is critical for maintaining efficacy of the therapeutic vaccine.

Assessment of a novel biliary-specific near-infrared fluorescent dye (BL-760) for intraoperative detection of bile ducts and biliary leaks during hepatectomy in a preclinical swine model.

OBJECTIVES: Postoperative bile leakage is a common complication of hepatobiliary surgery and frequently requires procedural intervention. Bile-label 760 (BL-760), a novel near-infrared dye, has emerged as a promising tool for identifying biliary structures and leakage, owing to its rapid excretion and strong bile specificity. This study aimed to assess the intraoperative detection of biliary leakage using intravenously administered BL-760 compared with intravenous (IV) and intraductal (ID) indocyanine green (ICG). MATERIALS AND METHODS: Laparotomy and segmental hepatectomy with vascular control were performed on two 25-30 kg pigs. ID ICG, IV ICG, and IV BL-760 were administered separately, followed by an examination of the liver parenchyma, cut liver edge, and extrahepatic bile ducts for areas of leakage. The duration of intra- and extrahepatic fluorescence detection was assessed, and the target-to-background (TBR) of the bile ducts to the liver parenchyma was quantitatively measured. RESULTS: In Animal 1, after intraoperative BL-760 injection, three areas of leaking bile were identified within 5 min on the cut liver edge with a TBR of 2.5-3.8 that was not apparent to the naked eye. In contrast, after IV ICG administration, the background parenchymal signal and bleeding obscured the areas of bile leakage. A second dose of BL-760 demonstrated the utility of repeated injections, confirming two of the three previously visualized areas of bile leakage and revealing one previously unseen leak. In Animal 2, neither ID ICG nor IV BL-760 injections showed obvious areas of bile leakage. However, fluorescence signals were observed within the superficial intrahepatic bile ducts after both injections. CONCLUSIONS: BL-760 enables the rapid intraoperative visualization of small biliary structures and leaks, with the benefits of fast excretion, repeatable intravenous administration, and high-fluorescence TBR in the liver parenchyma. Potential applications include the identification of bile flow in the portal plate, biliary leak or duct injury, and postoperative monitoring of drain output. A thorough assessment of the intraoperative biliary anatomy could limit the need for postoperative drain placement, a possible contributor to severe complications and postoperative bile leak.

Polymer nanomaterials for use as adjuvant surgical tools.

Materials employed in the treatment of conditions encountered in surgical and clinical practice frequently face barriers in translation to application. Shortcomings can be generalized through their reduced mechanical stability, difficulty in handling, and inability to conform or adhere to complex tissue surfaces. To overcome an amalgam of challenges, research has sought the utilization of polymer-derived nanomaterials deposited in various fashions and formulations to improve the application and outcomes of surgical and clinical interventions. Clinically prevalent applications include topical wound dressings, tissue adhesives, surgical sealants, hemostats, and adhesion barriers, all of which have displayed the potential to act as superior alternatives to current materials used in surgical procedures. In this review, emphasis will be placed not only on applications, but also on various design strategies employed in fabrication. This review is designed to provide a broad and thought-provoking understanding of nanomaterials as adjuvant tools for the assisted treatment of pathologies prevalent in surgery. This article is categorized under: Implantable Materials and Surgical Technologies > Nanomaterials and Implants Implantable Materials and Surgical Technologies > Nanoscale Tools and Techniques in Surgery.

Controlled Release of a Therapeutic Peptide in Sprayable Surgical Sealant for Prevention of Postoperative Abdominal Adhesions.

Formation of asymmetric, rigid scar tissue known as surgical adhesions is caused by traumatic disruption of mesothelial-lined surfaces in surgery. A widely adopted prophylactic barrier material (Seprafilm) for the treatment of intra-abdominal adhesions is applied operatively as a pre-dried hydrogel sheet but has reduced translational efficacy due its brittle mechanical properties. Topically administered peritoneal dialysate (Icodextrin) and anti-inflammatory drugs have failed to prevent adhesions due to an uncontrolled release profile. Hence, inclusion of a targeted therapeutic into a solid barrier host matrix with improved mechanical properties could provide dual utility in adhesion prevention and as a surgical sealant. Spray deposition of poly(lactide-co-caprolactone) (PLCL) polymer fibers through solution blow spinning has yielded a tissue-adherent barrier material with previously reported adhesion prevention efficacy due to a surface erosion mechanism that inhibits deposition of inflamed tissue. However, such an approach uniquely presents an avenue for controlled therapeutic release through mechanisms of diffusion and degradation. Such a rate is kinetically tuned via facile blending of "high" molecular weight (HMW) and "low" molecular weight (LMW) PLCL with slow and fast biodegradation rates, respectively. Here, we explore viscoelastic blends of HMW PLCL (70% w/v) and LMW PLCL (30% w/v) as a host matrix for anti-inflammatory drug delivery. In this work, COG133, an apolipoprotein E (ApoE) mimetic peptide with potent anti-inflammatory properties was selected and tested. In vitro studies with PLCL blends presented low (∼30%) and high (∼80%) percent release profiles over a 14-day period based on the nominal molecular weight of the HMW PLCL component. Two independent mouse models of cecal ligation and cecal anastomosis significantly reduced adhesion severity versus Seprafilm, COG133 liquid suspension, and no treatment control. The synergy of physical and chemical methods in a barrier material with proven preclinical studies highlights the value of COG133-loaded PLCL fiber mats in effectively dampening the formation of severe abdominal adhesions.

Sprayable tissue adhesive with biodegradation tuned for prevention of postoperative abdominal adhesions.

Adhesions are dense, fibrous bridges that adjoin tissue surfaces due to uncontrolled inflammation following postoperative mesothelial injury. A widely used adhesion barrier material in Seprafilm often fails to prevent transverse scar tissue deposition because of its poor mechanical properties, rapid degradation profile, and difficulty in precise application. Solution blow spinning (SBS), a polymer fiber deposition technique, allows for the placement of in situ tissue-conforming and tissue-adherent scaffolds with exceptional mechanical properties. While biodegradable polymers such as poly(lactic-co-glycolic acid) (PLGA) have desirable strength, they exhibit bulk biodegradation rates and inflammatory profiles that limit their use as adhesion barriers and result in poor tissue adhesion. Here, viscoelastic poly(lactide-co-caprolactone) (PLCL) is used for its pertinent biodegradation mechanism. Because it degrades via surface erosion, spray deposited PLCL fibers can dissolve new connections formed by inflamed tissue, allowing them to function as an effective, durable, and easy-to-apply adhesion barrier. Degradation kinetics are tuned to match adhesion formation through the design of PLCL blends comprised of highly adhesive "low"-molecular weight (LMW) constituents in a mechanically robust "high"-molecular weight (HMW) matrix. In vitro studies demonstrate that blending LMW PLCL (30% w/v) with HMW PLCL (70% w/v) yields an anti-fibrotic yet tissue-adhesive polymer sealant with a 14-day erosion rate countering adhesion formation. PLCL blends additionally exhibit improved wet tissue adhesion strength (~10 kPa) over a 14-day period versus previously explored biodegradable polymer compositions, such as PLGA. In a mouse cecal ligation model, select PLCL blends significantly reduce abdominal adhesions severity versus no treatment and Seprafilm-treated controls.

Sparing the Perineal Body: A Modification of the Posterior Sagittal Anorectoplasty for Anorectal Malformations with Rectovestibular Fistulae.

BACKGROUND: The posterior sagittal anorectoplasty (PSARP) used to repair an anorectal malformation (ARM) with a rectovestibular fistula involves incising the perineal body skin and the sphincter muscles and a posterior sagittal incision to the coccyx. Perineal body dehiscence is the most common and morbid complication post-PSARP which can have a negative impact on future bowel control. With consideration of all the other approaches described to repair this anomaly, we developed a perineal body sparing modification of the standard PSARP technique. METHODS: Four patients with ARM with a rectovestibular fistula were repaired with a perineal body sparing modified PSARP at a single institution between 2020 and 2021. The incision used was limited, involving only the length of the anal sphincter, with no incision anterior or posterior to the planned anoplasty. Dissection of the distal rectum and fistula was performed without cutting the perineal body. Once the distal rectum was mobilized off the posterior vaginal wall and out of the vestibule, the perineal body muscles, where the fistula had been, were reinforced and an anoplasty was then performed. RESULTS: Operative time was the same as for a standard PSARP. There were no intraoperative or postoperative complications. No postoperative dilations were performed. All patients healed well with an excellent cosmetic result. All are too young to assess for bowel control. CONCLUSION: We present a new technique, a modification of the traditional PSARP for rectovestibular fistula, which spares the perineal body. This approach could eliminate the potential complication of perineal body dehiscence.

Unsupervised and quantitative intestinal ischemia detection using conditional adversarial network in multimodal optical imaging.

Purpose: Intraoperative evaluation of bowel perfusion is currently dependent upon subjective assessment. Thus, quantitative and objective methods of bowel viability in intestinal anastomosis are scarce. To address this clinical need, a conditional adversarial network is used to analyze the data from laser speckle contrast imaging (LSCI) paired with a visible-light camera to identify abnormal tissue perfusion regions. Approach: Our vision platform was based on a dual-modality bench-top imaging system with red-green-blue (RGB) and dye-free LSCI channels. Swine model studies were conducted to collect data on bowel mesenteric vascular structures with normal/abnormal microvascular perfusion to construct the control or experimental group. Subsequently, a deep-learning model based on a conditional generative adversarial network (cGAN) was utilized to perform dual-modality image alignment and learn the distribution of normal datasets for training. Thereafter, abnormal datasets were fed into the predictive model for testing. Ischemic bowel regions could be detected by monitoring the erroneous reconstruction from the latent space. The main advantage is that it is unsupervised and does not require subjective manual annotations. Compared with the conventional qualitative LSCI technique, it provides well-defined segmentation results for different levels of ischemia. Results: We demonstrated that our model could accurately segment the ischemic intestine images, with a Dice coefficient and accuracy of 90.77% and 93.06%, respectively, in 2560 RGB/LSCI image pairs. The ground truth was labeled by multiple and independent estimations, combining the surgeons' annotations with fastest gradient descent in suspicious areas of vascular images. The total processing time was 0.05 s for an image size of 256 × 256 . Conclusions: The proposed cGAN can provide pixel-wise and dye-free quantitative analysis of intestinal perfusion, which is an ideal supplement to the traditional LSCI technique. It has potential to help surgeons increase the accuracy of intraoperative diagnosis and improve clinical outcomes of mesenteric ischemia and other gastrointestinal surgeries.

Tumor Apolipoprotein E is a key checkpoint blocking anti-tumor immunity in mouse melanoma.

Immunotherapy is a key modality in the treatment of cancer, but many tumors remain immune resistant. The classic mouse model of B16-F10 melanoma is immune resistant even in the face of checkpoint inhibition. Apolipoprotein E (apoE), a known immune suppressant is strikingly elevated in many human tumors, but its role in cancer immunology is not defined. We investigated the role of apoE in the immune micro-environment using a mouse melanoma model. We demonstrate that ApoE is -highly expressed in wild-type B16-F10 melanoma and serum levels progressively increase as tumors grow. The conditioned media from wild type ApoE secreting melanoma cells suppress T-cell activation in vitro while this suppressive effect is absent in conditioned media from ApoE knock out tumor cells. Mechanistically, apoE induces IL-10 secreting dendritic cells and stimulates T-cell apoptosis and arrest partially via the lrp8 receptor. Ablating ApoE in mice inoculated with tumor cells enabled tumor cell rejection and was associated with induction of immune pathway activation and immune cell infiltration. Tumor secreted apoE appears to be a potent immune cell checkpoint and targeting apoE is associated with enhanced tumor immunity in the mouse melanoma model.

Evaluation of healing outcomes combining a novel polymer formulation with autologous skin cell suspension to treat deep partial and full thickness wounds in a porcine model: a pilot study.

Autologous skin cell suspensions (ASCS) can treat burns of varying depths with the advantage of reduced donor site wound burden. The current standard primary dressing for ASCS is a nonabsorbant, non-adherent, perforated film (control) which has limited conformability over heterogeneous wound beds and allows for run-off of the ASCS. To address these concerns, a novel spray-on polymer formulation was tested as a potential primary dressing in porcine deep partial thickness (DPT) and full thickness (FT) wounds. It was hypothesized that the polymer would perform as well as control dressing when evaluating wound healing and scarring. DPT or FT wounds were treated with either a spray-on poly(lactic-co-glycolic acid) (PLGA) and poly(lactide-co-caprolactone) (PLCL) formulation or control ASCS dressings. Throughout the experimental time course (to day 50), we found no significant differences between polymer and control wounds in % re-epithelialization, graft-loss, epidermal or dermal thickness, or % dermal cellularity in either model. Pigmentation, erythema, elasticity, and trans-epidermal water loss (TEWL), were not significantly altered between the treatment groups, but differences between healing wounds/scars and un-injured skin were observed. No cytotoxic effect was observed in ASCS incubated with the PLGA and PLCL polymers. These data suggest that the novel spray-on polymer is a viable option as a primary dressing, with improved ease of application and conformation to irregular wounds. Polymer formulation and application technique should be a subject of future research.

Recidivism following childhood maltreatment necessitating inpatient care in the United States.

INTRODUCTION: Non-accidental trauma (NAT) is one of the common causes of injury in children in the United States (US). Abuse and maltreatment affect 2 per 100,000 children annually and may go unrecognized. The aim of this study to quantify the recidivistic nature of NAT in the US pediatric population. METHODS: The National Readmissions Database (2007-2015) was queried for pediatric (≤18y) trauma patients. Children presenting for non-accidental trauma were further identified. Data was obtained on demographic, clinical, and hospital-level characteristics. Body regions with an Abbreviated Injury Scale (AIS) greater than three were further identified. Multivariable logistic regression analysis (adjusting for age, gender, insurance status, year, Injury Severity Score [ISS], hospital region, and mechanism of injury) was utilized to determine factors influencing unintentional and intentional (assault) non-accidental traumatic injuries. RESULTS: NAT represents 1.6% (n = 4,634/286,508) of all pediatric trauma. The median age of presentation was <1y [IQR:0-3] with a male predominance (56.2%). Median ISS was 9 [IQR:2-16]. 87.5% of incidents represented assault (intentional). The most commonly affected body region was the head and neck (32.8%), followed by the extremities (11.4%) and soft tissue trauma or burns (6.3%). Penetrating trauma accounted for 18% of these injuries. 3.2% were readmitted to the hospital for a recurrent episode. 85.5% presented to the hospital for their initial evaluation. Mortality rates were 3.8% for those re-admitted to the hospital. The most common perpetrators were other specified persons known to the family, followed by fathers and mothers. CONCLUSION: Although uncommon, recidivism, after an initial episode of NAT, can have devastating consequences. The majority of the perpetrators of abuse are individuals known to the patient or family. Health policy aimed towards developing preventative strategies is needed to facilitate early recognition and tackle abuse in children. LEVEL OF EVIDENCE: III. TYPE OF EVIDENCE: Case Control Study.

The impact of regionality and hospital status on mortality associated with non-accidental trauma.

INTRODUCTION: Non-accidental trauma (NAT) affects 2 per 100,000 children annually in the US and may go unrecognized. The aim of this study to quantify the burden of NAT and to evaluate regional variations in mortality. METHODS: The Kids Inpatient Database (2000-2012) was queried for pediatric patients presenting with a diagnosis of NAT. Data was obtained on demographic, clinical and hospital-level characteristics. Primary outcome measure was mortality. Multivariable logistic regression models for age, sex, race/ethnicity, insurance status, income quartile, hospital volume, region (Northeast, South, West and Midwest), teaching status, and injury severity scores. RESULTS: NAT represented 1.92% (n = 15,999) of all trauma patients. Mortality rates were 3.98% for patients presenting with NAT. African American children had a higher likelihood of mortality compared to White children (OR[95%CI]:1.35[1.03-1.79]), however, this effect was not statistically significant for patients being treated at designated children's hospitals (OR[95%CI]:1.23(0.78-1.95) and urban facilities (OR[95%CI]:1.30[0.99-1.72]). Statistically significant regional variations in mortality, lost significance for patients treated at designated children's hospitals (p > 0.05). CONCLUSION: NAT has devastating consequences and is associated with a high mortality rate. Treatment at designated children's hospitals results in the loss of variation in mortality, resulting in diminished disparities and improved outcomes. These findings align with current trends towards the "regionalization of pediatric health care" and reflects the value of regional transfer centers that are.

Biodegradable, Tissue Adhesive Polyester Blends for Safe, Complete Wound Healing.

Pressure-sensitive adhesives typically used for bandages are nonbiodegradable, inhibiting healing, and may cause an allergic reaction. Here, we investigated the effect of biodegradable copolymers with promising thermomechanical properties on wound healing for their eventual use as biodegradable, biocompatible adhesives. Blends of low molecular weight (LMW) and high molecular weight (HMW) poly(lactide-co-caprolactone) (PLCL) are investigated as tissue adhesives in comparison to a clinical control. Wounds treated with PLCL blend adhesives heal completely with similar vascularization, scarring, and inflammation indicators, yet require fewer dressing changes due to integration of the PLCL adhesive into the wound. A blend of LMW and HMW PLCL produces an adhesive material with significantly higher adhesive strength than either neat polymer. Wound adhesion is comparable to a polyurethane bandage, utilizing conventional nonbiodegradable adhesives designed for extremely strong adhesion.

Mediated Electrochemical Probing: A Systems-Level Tool for Redox Biology.

Biology uses well-known redox mechanisms for energy harvesting (e.g., respiration), biosynthesis, and immune defense (e.g., oxidative burst), and now we know biology uses redox for systems-level communication. Currently, we have limited abilities to "eavesdrop" on this redox modality, which can be contrasted with our abilities to observe and actuate biology through its more familiar ionic electrical modality. In this Perspective, we argue that the coupling of electrochemistry with diffusible mediators (electron shuttles) provides a unique opportunity to access the redox communication modality through its electrical features. We highlight previous studies showing that mediated electrochemical probing (MEP) can "communicate" with biology to acquire information and even to actuate specific biological responses (i.e., targeted gene expression). We suggest that MEP may reveal an extent of redox-based communication that has remained underappreciated in nature and that MEP could provide new technological approaches for redox biology, bioelectronics, clinical care, and environmental sciences.

Improved Nerve Visualization in Head and Neck Surgery Using Mueller Polarimetric Imaging: Preclinical Feasibility Study in a Swine Model.

BACKGROUND AND OBJECTIVES: Meticulous dissection and identification of nerves during head and neck surgery are crucial for preventing nerve damage. At present, nerve identification relies heavily on the surgeon's knowledge of anatomy, optionally combined with intraoperative neuromonitoring. Recently, optical techniques such as Mueller polarimetric imaging (MPI) have shown potential to improve nerve identification. STUDY DESIGN/MATERIALS AND METHODS: With institutional approval, seven 25-35 kg Yorkshire pigs underwent cervical incision in the central neck. Intraoperative images were obtained using our in-house MPI system. Birefringence maps from the MPI system were processed to quantify the values between 0 and 255 from different tissue types; an active contour model was applied to further improve nerve visualization on the corresponding color images. RESULTS: Among the seven pigs, the vagus nerves and recurrent laryngeal nerves were successfully differentiated with a mean intensity of 130.954 ± 20.611, which was significantly different (P < 0.05) from those of arteries (78.512 ± 27.78) and other surrounding tissues (82.583 ± 35.547). There were no imaging-related complications during the procedure. © 2021 Wiley Periodicals LLC. CONCLUSIONS: MPI is a potentially complementary intraoperative tool for nerve identification in adjacent tissues.

MYC oncogene is associated with suppression of tumor immunity and targeting Myc induces tumor cell immunogenicity for therapeutic whole cell vaccination.

BACKGROUND: MYC oncogene is deregulated in 70% of all human cancers and is associated with multiple oncogenic functions including immunosuppression in the tumor microenvironment. The role of MYC in the immune microenvironment of neuroblastoma and melanoma is investigated and the effect of targeting Myc on immunogenicity of cancer cells is evaluated. METHODS: Immune cell infiltrates and immunogenic pathway signatures in the context of MYCN amplification were analyzed in human neuroblastoma tumors and in metastatic melanoma. Dose response and cell susceptibility to MYC inhibitors (I-BET726 and JQ1) were determined in mouse cell lines. The influence of downregulating Myc in tumor cells was characterized by immunogenic pathway signatures and functional assays. Myc-suppressed tumor cells were used as whole cell vaccines in preclinical neuroblastoma and melanoma models. RESULTS: Analysis of immune phenotype in human neuroblastoma and melanoma tumors revealed that MYCN or c-MYC amplified tumors respectively are associated with suppressed immune cell infiltrates and functional pathways. Targeting Myc in cancer cells with I-BET726 and JQ1 results in cell cycle arrest and induces cell immunogenicity. Combining vaccination of Myc-inhibited tumor cells with checkpoint inhibition induced robust antitumor immunity and resulted in therapeutic cancer vaccine therapy in mouse neuroblastoma tumors. Despite vigorous antitumor immunity in the mouse melanoma model, upregulation of immunosuppressive pathways enabled tumor escape. CONCLUSIONS: This study demonstrates that the Myc oncogene is an appropriate target for inducing tumor cell immunogenicity and suggests that Myc-suppressed whole tumor cells combined with checkpoint therapy could be used for formulating a personalized therapeutic tumor vaccine.

A Team-Based Approach for Children With Congenital Cardiac Disease Undergoing Antireflux Procedure With Gastrostomy.

INTRODUCTION: Laparoscopic Nissen fundoplication with gastrostomy tube (LPNF-GT) placement is often indicated in children with congenital cardiac diseases (CCDs) for nutritional optimization. This study aims to evaluate institutional outcomes of LPNF-GT, with a team-based approach in operative management. METHODS: Five years of an institutional database at a tertiary care children's hospital was queried for LPNF-GT in children with CCDs. Descriptive analyses were performed. A national comparison was performed utilizing the 2012-2013 Pediatrics NSQIP database, using propensity score matching. Outcome measures of interest were operative-time, unplanned readmission, and 30-day mortality. RESULTS: A team-based approach was utilized in 51 cases. Median operative time was 68.5 (IQR: 48-89) minutes. All patients tolerated tube feeds postoperatively. All patients survived 30 days post surgery. When compared to 136 similarly matched children nationally, the risk-adjusted operative time with a team-based approach was 47.38 (12.43-82.33) minutes shorter (P < .05). There were no statistically significant differences in the likelihood of being in the hospital past 30 days, unplanned readmissions, and mortality (P > .05). CONCLUSION: LPNF-GT can be safely performed in children with CCDs. A team-based approach demonstrates improved operative time and achieved similar outcomes when compared nationally.

Tracheal Agenesis: Vertical Division of the Native Esophagus - A Novel Surgical Approach and Review of the Literature.

INTRODUCTION: Tracheal agenesis (TA) is rare and usually fatal. Few survivors with concomitant tracheoesophageal fistulae (TEF) who underwent ligation of the distal esophagus with creation of a spit-fistula and neo-trachea from the proximal esophagus exist. We report a novel surgical technique whereby the esophagus is divided longitudinally to preserve a functional alimentation tract and a parallel neo-trachea. We review the literature of reported cases, including survivors beyond 12 months. METHODS: Case report and literature review. RESULTS: A female infant with prenatal polyhydramnios was born at 35 weeks gestation with immediate respiratory distress and absent cry. Oxygenation was maintained with a laryngeal mask airway. Despite a normal appearing larynx, she could not be intubated and emergent neck exploration disclosed no cervical trachea. The patient was placed on extra corporeal membranous oxygenation (ECMO), and later diagnosed with TA, Floyd Type I. Parental desire for reconstruction but refusal of a spit-fistula necessitated a novel procedure. The esophagus was divided longitudinally via a microstapler to preserve the original alimentary tract and create a parallel neo-trachea originating from the TEF and terminating as a cervical stoma. The healing process was complicated but the baby was ultimately discharged to home where she developed normally neurologically until succumbing one night to accidental decannulation at 16 months of age. CONCLUSION: We describe a novel surgical approach to manage TA. This includes avoiding creation of a spit fistula and preserving the native esophagus. We then survey the literature, reporting the survivorship duration and operative management of 174 reported cases of TA.

Variations in the management of adolescent adnexal torsion at a single institution and the creation of a unified care pathway.

PURPOSE: Adnexal torsion is a gynecologic emergency, requiring intervention for tissue preservation. At our institution, torsion is managed by pediatric surgeons or gynecologists. We evaluated differences between specialties to streamline evaluation for children with gynecological emergencies, develop a clinical pathway, and prevent care delays. METHODS: A retrospective review of adolescents undergoing intervention for adnexal torsion from 2004-2018 was performed. Differences in time to intervention, operation duration, the procedure performed, and length of stay (LOS) between the specialties were analyzed. RESULTS: Eighty-six patients underwent 94 operations for presumed adnexal torsion with 87 positive cases. Pediatric surgeons performed 60 operations and 34 cases were performed by gynecologists. Preservation of fertility was the goal in both cohorts and the rate of oophoropexy, cystectomy, and oophorectomy were similar between the cohorts (p = 0.14, p = 1.0, p = 0.39, respectively). There was no difference in intra-operative time (p = 0.69). LOS was shorter in the gynecology cohort (median 1 day [1-2] vs. 2 days [2-3], p > 0.001). CONCLUSIONS: Adnexal torsion is a time-sensitive diagnosis requiring prompt intervention for ovarian or fallopian tube preservation. A multidisciplinary institutional care pathway should be developed and implemented.