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Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death in the United States and worldwide. HCC screening among patients at elevated risk is associated with improved early detection and overall survival, but current ultrasound-based screening strategies are challenged by low adherence and suboptimal sensitivity. Blood-based screening tests have the potential to enhance adherence and improve early-stage HCC detection if they can demonstrate favorable performance compared with ultrasound-based screening. Here we present the design and rationale for ALTUS (A lternative to Ultrasound), a prospective, longitudinal, multicenter study in the United States to investigate the performance of the multi-target HCC blood test (mt-HBT) for the detection of HCC in a screening population. Methods: Adults with liver cirrhosis or chronic hepatitis B infection will be enrolled to undergo standard-of-care screening imaging and concurrent blood collection for the mt-HBT. All participants will undergo contrast-enhanced CT or MRI imaging with central radiology LI-RADS assessment as the reference method to determine HCC status. Participants without an identified malignancy will undergo a second screening visit and blood collection, and longitudinal clinical and imaging data will be collected up to 18 months from enrollment. The primary study objectives are to demonstrate that the mt-HBT is non-inferior to ultrasound for early-stage HCC sensitivity and to assess mt-HBT HCC specificity. The secondary objective is to assess mt-HBT overall sensitivity. Results: ALTUS is in progress with readout of the primary analysis expected in 2025. Conclusions: This prospective head-to-head comparison of the mt-HBT versus ultrasound will provide novel data regarding the performance and utility of the mt-HBT for HCC screening.

Abstract Background The pediatric resuscitation and trauma outcome (PRESTO) model was developed to aid comparisons of risk‐adjusted mortality after injury in low‐ and middle‐income countries (LMICs). We sought to validate PRESTO using data from a middle‐income country (MIC) trauma registry and compare its performance to the Pediatric Trauma Score (PTS), Revised Trauma Score, and pediatric age‐adjusted shock index (SIPA). Methods We included children (age < 15 years) admitted to a single trauma center in South Africa from December 2012 to January 2019. We excluded patients missing variables necessary for the PRESTO model—age, systolic blood pressure, pulse, oxygen saturation, neurologic status, and airway support. Trauma scores were assigned retrospectively. PRESTO's previously high‐income country (HIC)‐validated optimal threshold was compared to MIC‐validated threshold using area under the receiver operating characteristic curves (AUROC). Prediction of in‐hospital death using trauma scoring systems was compared using ROC analysis. Results Of 1160 injured children, 988 (85%) had complete data for calculation of PRESTO. Median age was 7 (IQR: 4, 11), and 67% were male. Mortality was 2% ( n = 23). Mean predicted mortality was 0.5% (range 0–25.7%, AUROC 0.93). Using the HIC‐validated threshold, PRESTO had a sensitivity of 26.1% and a specificity of 99.7%. The MIC threshold showed a sensitivity of 82.6% and specificity of 89.4%. The MIC threshold yielded superior discrimination (AUROC 0.86 [CI 0.78, 0.94]) compared to the previously established HIC threshold (0.63 [CI 0.54, 0.72], p < 0.0001). PRESTO showed superior prediction of in‐hospital death compared to PTS and SIPA (all p < 0.01). Conclusion PRESTO can be applied in MIC settings and discriminates between children at risk for in‐hospital death following trauma. Further research should clarify optimal decision thresholds for quality improvement and benchmarking in LMIC settings.

AbstractIntroductionWe aimed to expand on the global surgical discussion around splenic trauma in order to understand locally and clinically relevant factors for operative (OP) and non‐operative management (NOM) of splenic trauma in a South African setting.MethodsA retrospective cohort study was performed using 2013–2017 data from the Pietermaritzburg Metropolitan Trauma Service. All adult patients (≥15 years) were included. Those managed with OP or NOM for splenic trauma were identified and analyzed descriptively. Multiple logistic regression analysis identified patients and clinical factors associated with management type.ResultsThere were 127 patients with splenic injury. Median age was 29 [19–35] years with 42 (33%) women and 85 (67%) men. Blunt injuries occurred in the majority (81, 64%). Organ Injury Scale (OIS) grades included I (25, 20%), II (43, 34%), III (36, 28%), IV (15, 11%), and V (8, 6%). Nine patients expired. On univariate analysis, increasing OIS was associated with OP management, need for intensive care unit (ICU) admission, and hospital and ICU duration of stay, but not mortality. In patients with a delayed compared to early presentation, ICU utilization (62% vs. 36%, p = 0.008) and mortality (14% vs. 4%, p = 0.03) were increased. After adjusting for age, sex, presence of shock, and splenic OIS, penetrating trauma (adjusted odds ratio, 5.7; 95%CI, 1.7–9.8) and admission lactate concentration (adjusted odds ratio, 1.4; 95%CI 1.1–1.9) were significantly associated with OP compared to NOM (p = 0.002; area under the curve 0.81).ConclusionsWe have identified injury mechanism and admission lactate as factors predictive of OP in South African patients with splenic trauma. Timely presentation to definitive care affects both ICU duration of stay and mortality outcomes. Future global surgical efforts may focus on expanding non‐operative management protocols and improving pre‐hospital care in patients with splenic trauma.

AbstractBackgroundSnake envenomation is associated with major morbidity especially in low‐ and middle‐income countries and may require fasciotomy. We determined patient factors associated with the need for fasciotomy after venomous snake bites in children located in KwaZulu‐Natal, South Africa.MethodsSingle institutional review of historical data (2012–2017) for children (<18 years) sustaining snake envenomation was performed. Clinical data, management, and outcomes were abstracted. Syndromes after snake bite were classified according to Blaylock nomenclature: progressive painful swelling (PPS), progressive weakness (PW), or bleeding (B), as it is difficult to reliably identify the species of snake after a bite. Comparative and multivariable analyses to determine factors associated with fasciotomy were performed.ResultsThere were 72 children; mean age was 7 (±3) years, 59% male. Feet were most commonly affected (n = 27, 38%) followed by legs (n = 18, 25%). Syndromes (according to Blaylock) included PPS (n = 63, 88%), PW (n = 5, 7%), and B (n = 4, 5%). Eighteen patients underwent fasciotomy, and one required above knee amputation. Nine patients received anti‐venom. Few patients (15%) received prophylactic beta‐lactam antibiotics. Hemoglobin < 11 mg/dL, leukocytosis, INR >1.2, and age‐adjusted shock index were associated with fasciotomy. On regression, age‐adjusted shock index and hemoglobin concentration < 11 mg/dL, presentation >24 h after snake bite, and INR >1.2 were independently associated with fasciotomy. Model sensitivity was 0.89 and demonstrated good fit.ConclusionsPatient factors were associated with the fasciotomy. These factors, coupled with clinical examination, may identify those who need early operative intervention. Improving time to treatment and the appropriate administration of anti‐venom will minimize the need for surgery.Level of evidenceIII

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.

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.