Hernandez, Matthew C.

AbstractBackgroundAcute appendicitis is a common pediatric surgical emergency; however, there are few grading systems to assign disease severity. The American Association for the Surgery of Trauma (AAST) recently developed a grading system for a variety of emergency surgical conditions, including appendicitis. The severity of acute appendicitis in younger patients in KwaZulu‐Natal (South Africa) is unknown. We aimed to describe the disease severity in this patient population using the AAST grading system hypothesizing that the AAST grade would correlate with morbidity, management type, and duration of stay.MaterialsSingle institutional review of patients <18 years old with a final diagnosis of acute appendicitis during 2010–2016 in KwaZulu‐Natal, South Africa, was performed. Demographics, physiologic and symptom data, procedural details, postoperative complications, and Clavien–Dindo classification were abstracted. AAST grades were generated based on intraoperative findings. Summary, univariate, and nominal logistic regression analyses were performed to compare AAST grade and outcomes.ResultsA total of 401 patients were identified with median [IQR] age of 11 [5–13], 65% male. Appendectomy was performed in all patients; 2.4% laparoscopic, 37.6% limited incision, and 60% midline laparotomy. Complications occurred in 41.6%, most commonly unplanned relaparotomy (22.4%), surgical site infection (8.9%), pneumonia (7.2%), and acute renal failure (2.9%). Complication rate and median length of stay increased with greater AAST grade (all p < 0.001). AAST grade was independently associated with increased risk of complications.ConclusionPediatric appendicitis is a morbid disease in a developing middle‐income country. The AAST grading system is generalizable and accurately corresponds with management strategies as well as key clinical outcomes.Level of evidenceRetrospective study, Level IV.Study typeRetrospective single institutional study.

AbstractBackgroundThe American Association for the Surgery of Trauma (AAST) anatomic severity grading system for adhesive small bowel obstruction (ASBO) has demonstrated to be a valid tool in North American patient populations. Using a multi‐national patient cohort, we retrospectively assessed the validity the AAST ASBO grading system and estimated disease severity in a global population in order to correlate with several key clinical outcomes.MethodsMulticenter retrospective review during 2012–2016 from four centers, Minnesota USA, Bologna Italy, Pietermaritzburg South Africa, and Bucharest Romania, was performed. Adult patients (age ≥ 18) with ASBO were identified. Baseline demographics, physiologic parameters, laboratory results, operative and imaging details, outcomes were collected. AAST ASBO grades were assigned by independent reviewers. Univariate and multivariable analyses with odds ratio (OR) and 95% confidence intervals (CIs) were performed.ResultsThere were 789 patients with a median [IQR] age of 58 [40–75] years; 47% were female. The AAST ASBO grades were I (n = 180, 23%), II (n = 443, 56%), III (n = 87, 11%), and IV (n = 79, 10%). Successful non‐operative management was 58%. Conversion rate from laparoscopy to laparotomy was 33%. Overall mortality and complication and temporary abdominal closure rates were 2, 46, and 4.7%, respectively. On regression, independent predictors for mortality included grade III (OR 4.4 95%CI 1.1–7.3), grade IV (OR 7.4 95%CI 1.7–9.4), pneumonia (OR 5.6 95%CI 1.4–11.3), and failing non‐operative management (OR 2.4 95%CI 1.3–6.7).ConclusionThe AAST EGS grade can be assigned with ease at any surgical facility using operative or imaging findings. The AAST ASBO severity grading system has predictive validity for important clinical outcomes and allows for standardization across institutions, providers, and future research. Disease severity and outcomes varied between countries.Level of evidence IIIStudy type Retrospective multi‐institutional cohort study.

Tube thoracostomy (TT) insertion can serve as a life-saving adjunct for thoracic trauma. Unfortunately, suboptimal positioning using the open, standard of care technique is associated with complications resulting in impaired TT function. Using a porcine model, we aimed to determine whether a magnetic chest tube positioning system (MCTPS) could be utilized to direct the intrathoracic TT position. Using recently deceased cross-bred domestic swine, we performed TT using our MCTPS and the standard of care open technique. The operator held one magnet outside of the thorax. The second magnet was positioned at the distal aspect of the TT. The operator was tasked with positioning the TT to distinct premarked intra-thoracic locations under blinded conditions. The experiment was video-recorded through an open sternotomy incision. As a control, TT was inserted using the standard of care open technique. The utilization of MCTPS successfully directed TT from one premarked location to another in 4 of 5 attempts (80%). Conversely, the control TT without magnetic guidance failed to navigate the premarked intra-thoracic locations with 0 of 5 attempts successful (p = 0.05). Positional flaws after TT placement are common. We demonstrate the feasibility of the MCTPS as an alternative to traditional hand-guided technique under simulated TT insertion conditions. The MCTPS is possibly superior to the current standard of care technique of TT. Additional studies are needed to develop this emerging technology in humans.

AbstractBackgroundCoagulopathy can delay or complicate surgical diseases that require emergent surgical treatment. Prothrombin complex concentrates (PCC) provide concentrated coagulation factors which may reverse coagulopathy more quickly than plasma (FFP) alone. We aimed to determine the time to operative intervention in coagulopathic emergency general surgery patients receiving either PCC or FFP. We hypothesize that PCC administration more rapidly normalizes coagulopathy and that the time to operation is diminished compared to FFP alone.MethodsSingle institution retrospective review was performed for coagulopathic EGS patients during 2/1/2008 to 8/1/2016. Patients were divided into three groups (1) PCC alone (2) FFP alone and (3) PCC and FFP. The primary outcome was the duration from clinical decision to operate to the time of incision. Summary and univariate analyses were performed.ResultsCoagulopathic EGS patients (n = 183) received the following blood products: PCC (n = 20, 11%), FFP alone (n = 119, 65%) and PCC/FFP (n = 44, 24%). The mean (± SD) patient age was 71 ± 13 years; 60% were male. The median (IQR) Charlson comorbidity index was similar in all three groups (PCC = 5(4–6), FFP = 5(4–7), PCC/FFP = 5(4–6), p = 0.33). The mean (± SD) dose of PCC administered was similar in the PCC/FFP group and the PCC alone group (2539 ± 1454 units vs. 3232 ± 1684, p =. 09). The mean (±SD) time to incision in the PCC alone group was significantly lower than the FFP alone group (6.0 ± 3.6 vs. 8.8 ± 5.0 h, p = 0.01). The mean time to incision in the PCC + FFP group was also significantly lower than the FFP alone group (7.1 ± 3.6 vs. 8.8 ± 5.0, p = 0.03). The incidence of thromboembolic complications was similar in all three groups.ConclusionsPCC, alone or in combination with FFP, reduced INR and time to surgery effectively and safely in coagulopathic EGS patients without an apparent increased risk of thromboembolic events, when compared to FFP use alone.Level of evidenceIV single institutional retrospective review.

AbstractIntroductionAppendicitis is a significant economic and healthcare burden in low‐, middle‐, and high‐income countries. We aimed to determine whether urban and rural patient status would affect outcomes in appendicitis in a combined population regardless of country of economic status. We hypothesize that patients from rural areas and both high‐ and low‐middle‐income countries would have disproportionate outcomes and duration of symptoms compared to their urban counterparts.MethodsAdults (≥18 years) with appendicitis during 2010–2016 in South Africa and USA were reviewed using multi‐institutional data. Baseline demographic, operative details, durations of stay, and complications (Clavien–Dindo index) were collected. AAST grades were assigned by two independent reviewers based on operative findings. Summary, univariate, and multivariable analyses of rural and urban patients in both countries were performed.ResultsThere were 2602 patients with a median interquartile range [IQR] of 26 [18–40] years; 45% were female. Initial management included McBurney incisions (n = 458, 18%), laparotomy (n = 915, 35%), laparoscopic appendectomy (n = 1185, 45%), and laparoscopy converted to laparotomy (n = 44, 2%). Comparing rural versus urban patient status, there were increased overall median [IQR] AAST grades (3 [1–5] vs. 2 [1–3], p = 0.001), prehospital duration of symptoms (2 [1–5] vs. 2 [1–3], p = 0.001), complications (44.3 vs. 23%, p = 0.001), and need for temporary abdominal closure (20.3 vs. 6.9%, p = 0.001).ConclusionDespite socioeconomic status and country of origin, patients from more rural environments demonstrate poorer outcomes notwithstanding significant differences in overall disease severity. The AAST grading system may serve a potential benchmark to recognize areas with disparate disease burdens. This information could be used for strategic improvements for surgeon placement and availability.

AbstractBackgroundTube thoracostomy (TT) is a commonly performed procedure which is associated with significant complication rates. Currently, there is no validated taxonomy to classify and compare TT complications across different populations. This study aims to validate such TT complication taxonomy in a cohort of South African trauma patients.MethodsPost hoc analysis of a prospectively collected trauma database from Pietermaritzburg Metropolitan Trauma Service (PMTS) in South Africa was performed for the period January 2010 to December 2013. Baseline demographics, mechanism of injury and complications were collected and categorized according to published classification protocols. All patients requiring bedside TT were included in the study. Patients who necessitated operatively placed or image‐guided TT insertion were excluded. Summary and univariate analyses were performed.ResultsA total of 1010 patients underwent TT. The mean age was (±SD) of 26 ± 8 years. Unilateral TTs were inserted in n = 966 (96%) and bilateral in n = 44 (4%). Complications developed in 162 (16%) patients. Penetrating injury was associated with lower complication rate (11%) than blunt injury (26%), p = 0.0001. Higher complication rate was seen in TT placed by interns (17%) compared to TT placed by residents (7%), p = 0.0001. Complications were classified as: insertional (38%), positional (44%), removal (9%), infective/immunologic (9%), and instructional, educational or equipment related (0%).ConclusionsDespite being developed in the USA, this classification system is robust and was able to comprehensively assign and categorize all the complications of TT in this South African trauma cohort. A universal standardized definition and classification system permits equitable comparisons of complication rates. The use of this classification taxonomy may help develop strategies to improve TT placement techniques and reduce the complications associated with the procedure.Level of evidenceV.Study typeSingle Institution Retrospective review.

AbstractThe Hippo pathway effector YAP is implicated in the pathogenesis of cholangiocarcinoma (CCA). The Hippo pathway relies on signaling cross talk for its regulation. Given the importance of platelet derived growth factor receptor (PDGFR) signaling in CCA biology, our aim was to examine potential YAP regulation by PDGFR. We employed human and mouse CCA specimens and cell lines for these studies. Initially, we confirmed upregulation of PDGFRβ and PDGFR ligands in human and mouse CCA specimens and cell lines. YAP, a transcriptional co‐activator, was localized to the nucleus in human CCA specimens and a cell line, as well as patient derived xenografts (PDX). PDGFR pharmacologic inhibition led to a redistribution of YAP from the nucleus to cytosol and downregulation of YAP target genes in a human CCA cell line. siRNA silencing of PDGFR‐β similarly downregulated YAP target genes. YAP activation (nuclear localization and target gene expression) was regulated by Src family kinases (SFKs) downstream of PDGFR. SFK activity resulted in phosphorylation of YAP on tyrosine357 (YAPY357). The importance of YAPY357 phosphorylation in regulating YAP activation was confirmed utilizing the SB‐1 cell line, a mouse cell line expressing YAP S127A precluding canonical serine phosphorylation. PDGFR inhibition decreased cellular abundance of the survival protein Mcl‐1, a known YAP target gene, and accordingly increased cell death in CCA cells in vitro and in vivo. These preclinical data demonstrate that a PDGFR‐SFK cascade regulates YAP activation via tyrosine phosphorylation in CCA. Inhibiting this cascade may provide a viable therapeutic strategy for this human malignancy.

Abstract Background Tube thoracostomy (TT) can be an effective therapy for thoracic pathologies. Ineffective placement of TT is common and associated with significant complications. Complications require additional interventions to repair damaged tissues or replace dysfunctional TT. We hypothesize that complicated TT insertion increases cost to the hospital system. Methods Adult trauma patients requiring TT at a level 1 trauma center (2012–2013) were reviewed. Intraoperative or image‐guided TT placements were excluded. Baseline demographics and TT insertion cost (normalized and assigned by hospital billing records) were recorded. Costs included initial TT equipment, radiographs, and subsequent operative or radiologic intervention to correct TT complications. Complications were categorized using previously validated method. Secondary outcomes included: number of TT inserted, number of chest radiographs performed, and TT dwell time utilizing a standardized TT discontinuation protocol. Results A total of 154 patients with 246 TT were included. Ninety TT (37%) had complication. Complication categories are postremoval ( n = 15, 16.7%), insertional ( n = 13, 14.4%), positional ( n = 62, 68.9%). Overall median complicated TT cost was 9 times greater than uncomplicated TT insertion, p = 0.001. Insertional complications median cost 21 times greater than an uncomplicated, due to operative and radiologic interventions ( p = 0.0001). Positional and postremoval complication rates increased median cost by 3 times compared to uncomplicated TT ( p = 0.03). Operative or radiologic interventions ( n = 10) were performed for organ injury or uncontrolled hemo‐/pneumothorax. Increased dwell time median [IQR] was associated with complicated TT compared to uncomplicated 3 [1–5] versus 2 [1–3], p = 0.01. Conclusion TT is a common procedure. TT complications are often considered benign. However, patients with a complicated TT insertion, especially related to insertional subtypes, have markedly increased hospitalization costs due to need for operative or radiologic repair. Level of evidence Level V—retrospective study. Study type This is a retrospective single‐institution study.