Optimal Predictor of Gonadal Viability in Testicular Torsion: Time to Treat Versus Duration of Symptoms.

BACKGROUND: We hypothesize that in testicular torsion, the duration of symptoms (DoS) better correlates with predicting testicular viability than minimizing the "time-to-treat" (TtT) after presentation to a medical facility. MATERIALS AND METHODS: Medical records of male pediatric patients treated for suspected diagnosis of testicular torsion in the emergency department (ED) from January 1, 2016, to December 31, 2018, were retrospectively evaluated. Forty-one patients met inclusion criteria. Statistical analysis compared testicular viability based on TtT, DoS, and site of initial presentation. RESULTS: Testicular salvage rates for patients presenting directly to our ED was 56.3% with an average TtT of 2.5 h versus 77.8% and 1.96 h, respectively, for transferred patients. Overall testicular survival was not statistically impacted by the difference in TtT. Comparing DoS, an 84% testicular salvage rate (DoS < 24 h) versus a 15.4% salvage rate (DoS > 24 h) was shown in patients presenting directly to our ED (P ≤ 0.0001). Within the total population (n = 41), a significant difference was also shown (P ≤ 0.0001) when comparing overall testicular salvage rates in patients presenting with <24 h versus >24 h total DoS (84% versus 25%). CONCLUSIONS: These data reveal that an alternative predictor of testicular salvage rates is a DoS < 24 h. This is a meaningful metric when providing accurate preoperating counseling to parents and may be a better focus of quality improvement efforts surrounding this topic.

Single-Incision Laparoscopic Appendectomy in Children And Conversion to Multiport Appendectomy.

BACKGROUND: Single-incision laparoscopic appendectomy (SILA) in the pediatric population has been well described. Our children's hospital has adopted this modality for nearly all appendectomies. From our center's experience, we hoped to identify factors that portend conversion from SILA to multiport appendectomy. We compared our cohort of conventional three-port laparoscopic appendectomy (CLA) for outcomes including operative time, postop length of stay (LOS), complications, and readmission. MATERIALS AND METHODS: A retrospective chart review of patients who underwent appendectomy from 2012 to 2017 at our children's hospital was performed. The type of appendectomy performed, if the case required conversion to multiple ports, and perforation status were recorded. Demographic data identified included age, sex, and body mass index. Outcomes analyzed were operative time, LOS, and postoperative complication/readmission rate. RESULTS: Of 1001 appendectomies performed, 959 (95.9%) were initiated with plan for SILA, and 35 (3.5%) were initiated CLA. Of those initiated SILA, 884/959 (92.2%) were completed without additional port placement. Cases which were not able to be completed SILA were statistically significantly more likely to be male patients, have increased body mass index, or perforated appendicitis. When compared to cases initiated CLA, SILA remained statistically similar for readmission and LOS but had significantly faster operative time. CONCLUSIONS: SILA appears to be a safe and efficient modality for the treatment of appendicitis in pediatric populations with no increased morbidity. Parents of children who are obese, males, or present with perforation should be counseled regarding the possibility of additional port placement or considered for initiating conventional three-port laparoscopic appendectomy.

Image-guided percutaneous drainage vs. surgical repair of gastrointestinal anastomotic leaks: is there a difference in hospital course or hospitalization cost?

PURPOSE: To identify differences in hospital course and hospitalization cost when comparing image-guided percutaneous drainage with surgical repair for gastrointestinal anastomotic leaks. MATERIALS AND METHODS: A retrospective IRB-approved search using key words "leak" and/or "anastomotic" was performed on all adult CT reports from 2002 to 2011. CT examinations were reviewed for evidence of a postoperative gastrointestinal leak and assigned a confidence score of 1-5 (1 = no leak, 5 = definite leak). Patients with an average confidence score <4 were excluded. Type of surgery, patient data, method of leak management, number of hospital admissions, length of hospital stay, discharge disposition, number of CT examinations, number of drains, and hospitalization costs were collected. RESULTS: One hundred thirty-nine patients had radiographic evidence of a gastrointestinal anastomotic leak (esophageal, gastric, small bowel or colonic). Nine patients were excluded due to low confidence scores. Twenty-seven patients underwent surgical repair (Group A) and 103 were managed entirely with percutaneous image-guided drainage (Group B). There was no significant difference in patient demographics or number of hospital admissions. Patients in Group A had longer median hospital stays compared to Group B (48 vs. 32 days, p = 0.007). The median total hospitalization cost for Group A was more than twice that for Group B ($99,995 vs. $47,838, p = 0.001). Differences in hospital disposition, number of CT examinations, number of drains, and time between original surgery and first CT examination were statistically significant. CONCLUSION: Gastrointestinal anastomotic leaks managed by percutaneous drainage are associated with lower hospital cost and shorter hospital stays compared with surgical management.

Osteopontin regulates epithelial mesenchymal transition-associated growth of hepatocellular cancer in a mouse xenograft model.

OBJECTIVE: To determine the efficacy of osteopontin (OPN) targeting in hepatocellular cancer (HCC). SUMMARY/BACKGROUND: OPN is associated with HCC growth and metastasis and represents a unique therapeutic target. METHODS: OPN and epithelial-mesenchymal transition (EMT) markers, α-smooth muscle actin (SMA), vimentin, and tenascin-c, were measured in archived human HCC tissues from metastatic (n = 4) and nonmetastatic (n = 4) settings. Additional studies utilized human Sk-Hep-1 (high OPN expression) and Hep3b (low OPN expression) HCC cells. An RNA aptamer (APT) that avidly binds (Kd = 18 nM; t1/2 = 7 hours) and ablates OPN binding was developed. Adhesion, migration/invasion, and EMT markers were determined with APT or a mutant control aptamer (Mu-APT). RFP-Luc-Sk-Hep-1 were implanted into NOD-scid mice livers and followed by using bioluminescence imaging. After verification of tumor growth, at week 3, APT (0.5 mg/kg; n = 4) or Mu-APT (0.5 mg/kg; n = 4) was injected q48h. When mice were killed at week 8, tumor cells were reisolated and assayed for EMT markers. RESULTS: OPN and EMT markers were significantly increased in the metastatic cohort. APT inhibited Sk-Hep-1 adhesion and migration/invasion by 5- and 4-fold, respectively. APT significantly decreased EMT protein markers, SMA, vimentin, and tenascin-c. In contrast, APT did not alter Hep3B adhesion, or migration/invasion. EMT markers were slightly decreased. In the in vivo model, at weeks 6 to 8, APT inhibited HCC growth by more than 10-fold. SMA, vimentin, and tenascin-c mRNAs were decreased by 60%, 40%, and 49%, respectively, in RFP-positive Sk-Hep-1 recovered by fluorescence-activated cell sorting (P < 0.04 vs Mu-APT for all). CONCLUSIONS: APT targeting of OPN significantly decreases EMT and tumor growth of HCC.

Osteopontin is induced by hedgehog pathway activation and promotes fibrosis progression in nonalcoholic steatohepatitis.

UNLABELLED: Nonalcoholic steatohepatitis (NASH) is a leading cause of cirrhosis. Recently, we showed that NASH-related cirrhosis is associated with Hedgehog (Hh) pathway activation. The gene encoding osteopontin (OPN), a profibrogenic extracellular matrix protein and cytokine, is a direct transcriptional target of the Hh pathway. Thus, we hypothesize that Hh signaling induces OPN to promote liver fibrosis in NASH. Hepatic OPN expression and liver fibrosis were analyzed in wild-type (WT) mice, Patched-deficient (Ptc(+/-) ) (overly active Hh signaling) mice, and OPN-deficient mice before and after feeding methionine and choline-deficient (MCD) diets to induce NASH-related fibrosis. Hepatic OPN was also quantified in human NASH and nondiseased livers. Hh signaling was manipulated in cultured liver cells to assess direct effects on OPN expression, and hepatic stellate cells (HSCs) were cultured in medium with different OPN activities to determine effects on HSC phenotype. When fed MCD diets, Ptc(+/-) mice expressed more OPN and developed worse liver fibrosis (P < 0.05) than WT mice, whereas OPN-deficient mice exhibited reduced fibrosis (P < 0.05). In NASH patients, OPN was significantly up-regulated and correlated with Hh pathway activity and fibrosis stage. During NASH, ductular cells strongly expressed OPN. In cultured HSCs, SAG (an Hh agonist) up-regulated, whereas cyclopamine (an Hh antagonist) repressed OPN expression (P < 0.005). Cholangiocyte-derived OPN and recombinant OPN promoted fibrogenic responses in HSCs (P < 0.05); neutralizing OPN with RNA aptamers attenuated this (P < 0.05). CONCLUSION: OPN is Hh-regulated and directly promotes profibrogenic responses. OPN induction correlates with Hh pathway activity and fibrosis stage. Therefore, OPN inhibition may be beneficial in NASH.

Retrograde ascending aortic dissection as an early complication of thoracic endovascular aortic repair.

OBJECTIVE: Retrograde ascending aortic dissection (rAAD) is a potential complication of thoracic endovascular aortic repair (TEVAR), yet little data exist regarding its occurrence. This study examines the incidence, etiology, and outcome of this event. METHODS: A prospective institutional database was used to identify cases of acute rAAD following TEVAR from a cohort of 309 consecutive procedures from March 2005 (date of initial Food and Drug Administration approval) to September 2010. The database was analyzed for the complication of rAAD as well as relevant patient and operative variables. RESULTS: The incidence of rAAD was 1.9% (6/309); all cases occurred with proximal landing zone in the ascending aorta and/or arch (zones 0-2). All were identified in the perioperative period (range, 0-6 days) with 33% (2/6) 30-day/in-hospital mortality. Eighty-three percent (5/6) underwent emergent repair; one patient died without repair. rAAD patients were similar to the non-rAAD group (n = 303) across pertinent variables, including age, gender, race, and device size (all P > .1). rAAD incidence by aortic pathology was 1.0% (2/200) for aneurysm, 4.4% (4/91) for dissection, and 0% (0/18) for transection; P = .08. rAAD incidence by device was TAG (Gore) 1.0% (2/205), Talent (Medtronic) 4.7% (2/43), and Zenith TX2 (Cook) 3.6% (2/55). rAAD incidence was observed to be higher among patients with an ascending aortic diameter ≥ 4.0 cm (4.8% vs 0.9% for ascending diameter <4.0 cm); P = .047. Incidence was also higher with proximal landing zone in the native ascending aorta (zone 0) 6.9% (2/29) versus 1.4% for all others (4/280); P = .101. For patients with dissection pathology and an ascending aortic diameter ≥ 4.0 cm, 11% (3/28) suffered rAAD; with the combination of native ascending aorta (zone 0) landing zone measuring ≥ 4.0 cm, the incidence was 25% (2/8). Definitive diagnosis was by computed tomography angiography (n = 1), intraoperative transesophageal echocardiography (n = 3), intraoperative arteriography (n = 1), or postmortem autopsy (n = 1). CONCLUSIONS: rAAD is a lethal early complication of TEVAR, which may be more common when treating dissection, with devices utilizing proximal bare springs or barbs for fixation, with native zone 0 proximal landing zone and with ascending aortic diameter ≥ 4 cm. Combinations of these risk factors may be particularly high risk. Intraoperative imaging assessment of the ascending aorta should be conducted following TEVAR to avoid under-recognition. National database reporting of this complication is needed to ensure safety and proper application of emerging TEVAR technology.

Combined in-person and tele-delivered mobile school clinic: A novel approach for improving access to healthcare during school hours.

AIMS: We report a novel pilot project that allows access to healthcare for children and staff at school via a mobile clinic or telemedicine portal connected to the mobile clinic. The objectives of this pilot project were (a) to perform physicals for children not attached to a primary care physician; (b) to provide medical consultations and treatment for acute illnesses of students and staff, and (c) to lower absenteeism rates among students and staff. METHODS: In 2013, Ronald McDonald House Charities, a non-profit organization, partnered with Children's Hospital of Erlanger to provide a mobile clinic trademarked Ronald McDonald Care Mobile utilising a large, box-style truck equipped with examination rooms and a telemedicine portal. Initially, starting with three elementary schools in Bradley County, Tennessee, USA, the programme rapidly expanded to include schools in five other participating Tennessee counties. Only three schools in Bradley County have the option of in-person visits. All other schools access care via telemedicine portals. Funding is provided through multiple grants and community partners. If a student does have insurance, the insurance carrier is billed for the visit, but students without insurance are treated free of charge. Prior to the 2018-2019 school year, only limited data were collected. RESULTS: Our first goal was to perform physicals for children not attached to a primary care physician. During the 2018-2019 school year, 28 patients presented for a well-child check. However, 16 of these (57%) did not have a primary care physician. Of note, 19% of students presenting for any complaint did not have a primary care physician on file (172 students). All well-child checks were performed in-person on the Care Mobile. Our second goal was to provide medical consultations and treatment for acute illnesses. A total of 1446 persons were seen for sick visits. Of these, 424 were telemedicine visits (352 students and 72 staff), while 1022 were in-person visits. The five most common diagnoses that the nurse practitioner managed during the 2018-2019 school year included acute pharyngitis, acute upper respiratory infection, streptococcal pharyngitis, fever and acute maxillary sinusitis. Finally, our third goal was to lower absenteeism rates. There were 1446 sick person visits (1253 students and 193 staff). Twenty-two per cent of the students (276 persons) returned to class while 74% (142 persons) of staff returned to work. CONCLUSION: The mobile/telemedicine health clinic is a novel innovation to increase access to acute care and reduce school absenteeism among both students and staff, potentially saving schools hundreds to thousands of dollars.

Osteopontin promotes CCL5-mesenchymal stromal cell-mediated breast cancer metastasis.

The interaction between cancer and its local microenvironment can determine properties of growth and metastasis. A critical component of the tumor microenvironment in this context is the cancer-associated fibroblast (CAF), which can promote tumor growth, angiogenesis and metastasis. It has been hypothesized that CAF may be derived from mesenchymal stromal cells (MSC), derived from local or distant sources. However, the signaling mechanisms by which tumors and MSCs interact to promote CAF-dependent cancer growth are largely unknown. In this study with in vitro and in vivo models using MDA-MB231 human breast cancer cells, we demonstrate that tumor-derived osteopontin (OPN) induces MSC production of CCL5; the mechanism involves OPN binding to integrin cell surface receptors and activator protein-1 c-jun homodimer transactivation. In a murine xenograft model, concomitant inoculation of MSC with MDA-MB231 cells induces: (i) significantly increased growth and metastasis of MB231 cells and (ii) increased MSC migration to metastatic sites in lung and liver; this mechanism is both OPN and CCL5 dependent. MSCs retrieved from sites of metastases exhibit OPN-dependent expression of the CAF markers, α-smooth muscle actin, tenascin-c, CXCL12 (or stromal cell-derived factor 1) and fibroblast-specific protein-1 and the matrix metalloproteinases (MMP)-2 and MMP-9. Based upon these results, we propose that tumor-derived OPN promotes tumor progression via the transformation of MSC into CAF.

Osteopontin and protein kinase C regulate PDLIM2 activation and STAT1 ubiquitination in LPS-treated murine macrophages.

The molecular pathways regulating signal transducer and activator of transcription 1 (STAT1) levels in states of inflammation are incompletely understood. The suppressor of cytokine signaling, protein inhibitor of STAT, and SHP-1/2 tyrosine phosphatases ultimately regulate activity of STAT molecules. However, these mechanisms do not degrade STAT proteins. In this regard, using a murine macrophage model of LPS stimulation, we previously demonstrated that osteopontin (OPN) increased STAT1 ubiquitination and 26 S proteasome degradation via the ubiquitin E3 ligase, PDLIM2. In this study, we further characterize OPN-dependent activation of PDLIM2 in a model of LPS-stimulated RAW264.7 murine macrophages. We identify serine 137 as a protein kinase C-phosphorylation site in PDLIM2 that is required for ubiquitination of STAT1. PDLIM2 phosphorylation requires OPN expression. Using phospho-mutants and phospho-mimetic constructs of PDLIM2, our in vivo and in vitro ubiquitination studies confirm the role of PDLIM2 in formation and degradation of Ub-STAT1. The functional consequences of PDLIM2-mediated STAT1 degradation were confirmed using an IFN-γ-regulated transcription factor STAT1α reporter construct and chromatin immunoprecipitation assay for the inducible nitric-oxide synthase promoter. In a murine cecal ligation and puncture model of sepsis in wild-type and OPN (-/-) animals, OPN was necessary for PDLIM2 serine phosphorylation and STAT1 ubiquitination in bone marrow macrophages. We conclude that OPN and PDLIM2 are important regulators of STAT1-mediated inflammatory responses.

Pan-aortic hybrid treatment of mega-aorta syndrome.

Hybrid procedures combining traditional open and newer endovascular techniques are increasingly used to treat complex aortic disease. We present a novel approach for total aortic replacement, including hybrid repair of the arch and thoracoabdominal aorta, in a patient with "mega-aorta syndrome." A two-stage approach using a valve-sparing aortic root replacement, total arch replacement (stage I elephant trunk), and left carotid-axillary bypass was used to treat the root, proximal-mid arch, and left subclavian aneurysmal pathology. This was followed by a hybrid distal arch/Extent II thoracoabdominal aneurysm repair 3 months later. After 15 months follow-up, the patient remains asymptomatic with an intact repair, no endoleak, and normal ventricular and aortic valve function. This case demonstrates a novel "pan-aortic" hybrid approach for repair of extensive thoracic aortic disease.

Mycotic aneurysm of the thoracoabdominal aorta in a child with end-stage renal disease.

A 5-year-old child with nephrotic syndrome developed a mycotic saccular thoracoabdominal aortic aneurysm (TAAA) involving the visceral segment within a 4-month period following pneumococcal bacteremia and presumed spontaneous bacterial peritonitis (SBP). Due to continued aneurysm growth and progression to end-stage renal disease, TAAA repair was performed, followed by cadaveric kidney transplantation. This is the first known instance of mycotic aortic aneurysm formation as a consequence of SPB and the first report of TAAA repair in preparation for kidney transplantation in a child.

Comparison of Operative Experiences of PGY-1 and PGY-2 General Surgery Residents During Night-Float vs. 24-Hour Call Systems.

OBJECTIVE: We aimed to specifically compare the impact of a night-float system vs. a 24-hour call system on the number and types of cases performed by PGY-1 and PGY-2 general surgery residents to determine if both of these schedules could meet the ACGME first two-year 250 case minimum requirement, and if so, which schedule provided the best operative experience for PGY-1 and PGY-2 residents. DESIGN: This is a retrospective review of call schedules and operative case logs of PGY-1 and PGY-2 general surgery residents. Residents were separated into two groups based on type of call schedule: 24-hour vs. night-float. The case logs of PGY-1 and PGY-2 residents were obtained from the ACGME Case Log System and data analysis was performed between the two groups. SETTING: This study was performed at a general surgery residency at a hybrid academic center. PARTICIPANTS: Forty-three residents met inclusion criteria. Twenty-three were part of the night-float system and 20 were part of the 24-hour call system. RESULTS: Total cases and major cases for PGY-1 and PGY-2 years were compared between the two groups. The 24-hour call group had a significantly higher total number of cases than the night-float group (646.0 ± 181.5 vs. 504.8 ±148.9, p = 0.008). Major cases were also significantly higher in the 24-hour call group than the night-float group (418.5 ± 99.6 vs. 355 ± 99.5, p = 0.043). CONCLUSIONS: Both the 24-hour call and night-float systems were able to meet the ACGME first two year 250 case minimum requirement as well as follow work-hour guidelines. The 24-hour call system was associated with PGY-1 and PGY-2 residents having a better operative experience than the night-float system.

Robotic inguinal lymph node dissection for melanoma: a novel approach to a complicated problem.

BACKGROUND: Indications for superficial inguinal lymph node (ILN) dissection in melanoma include fine needle aspiration or clinically positive ILN and sentinel lymph nodes (SLN). Open inguinal lymphadenectomy may be complicated by poor wound healing, deep vein thrombosis, and lymphedema. Technical considerations and case series of a novel surgical approach, robotic inguinal lymphadenectomy, are presented. METHODS: This is a case series of four robotic ILN dissections for melanoma at a tertiary care facility. Each patient had previously diagnosed melanoma by lymph node biopsy. Physician and patient jointly decided on robotic procedure after disclosure of this novel approach. Demographic, complication, pathological outcome, estimated blood loss (EBL), operative time, and length of stay (LOS) data were collected. RESULTS: No cases were aborted due to technical difficulty. The median patient age was 44.5 years (range 22-53 years) and median BMI was 27.5 (range 20.4-40.2). Operative time range was 120-231 min and EBL from 0 to 100 mL. Median nodal count was 5.5 (range 1-14 nodes). Patient LOS ranged from 0 (discharged from post anesthesia care unit) to 96 h. There was one complication of port site cellulitis, one seroma formation, and no instances of lymphedema. To date, there have been no deaths or melanoma recurrences in this population. CONCLUSION: Recent data suggest a minimum node count of six to seven for inguinal dissection. Of our four dissections, two were above this threshold and there were minimal postoperative complications. Given our limited sample size, future focus should be on increasing the data on this approach to optimize surgical outcomes and oncologic results.

Comparative effectiveness of treatment strategies for severe splenic trauma in the pediatric population.

BACKGROUND: Splenic angioembolization (SAE) is increasingly used in the management of splenic injuries in adults, although its value in pediatric trauma is unclear. We sought to assess outcomes related to splenectomy vs SAE. METHODS: The National Trauma Data Bank was queried for patients 0 to 15 years of age from 2007 to 2011. Subgroup analysis of splenectomy vs SAE was performed for high-grade injuries using propensity analysis and inverse probability weighting. RESULTS: Of 11,694 children presenting with splenic trauma, over 90% were treated nonoperatively. Adjusted analysis of high-grade injuries included 265 children who underwent splenectomy and 199 who underwent SAE. The Injury Severity Score, number of transfusions, and complications rates were not significantly different between the 2 groups. Overall adjusted mortality for children with high-grade injuries was 13.4% following splenectomy and 10.0% following SAE (P = .31) CONCLUSION: Patients undergoing SAE for high-grade splenic trauma have comparable morbidity and mortality with splenectomy.

Diagnostic performance of MDCT in identifying closed loop small bowel obstruction.

PURPOSE: To assess the diagnostic performance of MDCT in the diagnosis of closed loop small bowel obstruction. MATERIALS AND METHODS: One hundred fifty patients with CT reports including "small bowel obstruction (SBO)" between 1/30/2011 and 12/4/2012 were included (65 men, 85 women, mean age 63 years). CT examinations were independently and blindly reviewed by five radiologists to determine the presence of closed loop obstruction (CL-SBO) and to assess findings of bowel ischemia. Clinical records were reviewed to determine management and operative findings. Using operative findings as a gold standard, reader agreement for the diagnosis of and the CT findings associated with CLO was analyzed using Pearson's correlation (r). Positive predictive value (PPV) and negative predictive value for the diagnosis of CL-SBO and CT signs of bowel ischemia were analyzed. RESULTS: Eighty-eight of 150 patients underwent operative intervention for SBO and 24/88 were considered CL-SBO operatively. Average reader sensitivity and specificity for CL-SBO was 53 % (95 % CI 44-63 %) and 83 % (95 % CI 79-87 %). Reader agreement on CL-SBO was poor to moderate (K = 0.39-0.63). Reader agreement for CT signs of bowel ischemia resulting in a diagnosis of CL-SBO was weak (r = 0.19-0.32). CONCLUSION: The CT diagnosis of CL-SBO is complex and associated imaging findings have variable sensitivity for predicting a closed loop operative diagnosis. CT can be helpful in excluding a closed loop component in patients with SBO.

Gastroesophageal heterotopia and HER2/neu overexpression in an adenocarcinoma arising from a small bowel duplication.

Small bowel duplications are congenital structures commonly lined by heterotopic gastric or pancreatic mucosa. Though benign in children, small bowel duplications have the potential for malignant degeneration in adulthood. Here, we present the first reported case of metastatic adenocarcinoma arising from a small bowel duplication lined by gastroesophageal mucosa. The cancer demonstrated overexpression of the HER2/neu oncoprotein and amplification of the HER2/neu gene. This represents the only report of HER2 overexpression in this type of lesion. The patient is being treated with traditional chemotherapeutic agents in addition to monoclonal antibody therapy directed at the HER2 protein, and has demonstrated a clinical benefit from treatment. This case demonstrates that the anatomic location of a mass may be distinct from its biological origin, and this difference may have important practical implications for diagnostic testing and treatment.