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We sought to determine the impact of the indication for shunt placement on shunt-related outcomes after major arterial injuries. We hypothesized that a shunt placed for damage control indications would be associated with an increase in shunt-related complications including shunt dislodgement, thrombosis, or distal ischemia.A prospective, multicenter study (eleven level one US trauma centers) of all adult trauma patients undergoing temporary intravascular shunts (TIVS) after arterial injury was undertaken (January 2017-May 2019). Exclusion criteria included age15years, shunt placement distal to popliteal/brachial arteries, isolated venous shunts, and death before shunt removal. Clinical variables were compared by indication and shunt-related complications. The primary endpoint was TIVS complications (thrombosis, migration, distal ischemia).The 66 patients who underwent TIVS were primarily young (30years [IQR 22-36]) men (85%), severely injured (ISS 17 [10-25]) by penetrating mechanisms (59%), and had their shunts placed for damage control (41%). After a median SDT of 198min [89-622], 9% experienced shunt-related complications. Compared by shunt placement indication (damage control shunts [n=27] compared to non-damage control shunts [n=39]), there were no differences in gender, mechanism, extremity AIS, MESS score, fractures, or surgeon specialty between the two groups (all p0.05). Patients with shunts placed for damage control indications had more severe injuries (ISS 23.5 compared to 13; SBP 100 compared to 129; GCS 11 compared to 15; lactate 11.5 compared to 3.6; all p0.05), and had more frequent shunt complication predictors, but damage control shunts did not have significantly more TIVS complications (11.1% compared to 7.7%, p=0.658). Shunt complication patients were discharged home less often (33% vs 65%; p0.05) but all survived.Shunts placed for damage control indications were not associated with shunt complications in this prospective, multicenter study.

Background: Early diagnosis and prompt debridement of necrotizing soft tissue infection (NSTI) improves the outcome. We sought to determine whether failure to admit NSTI patients to acute care surg...

Background Outcome data on the very elderly patients undergoing emergency general surgery (EGS) are sparse. We sought to examine short- and long-term mortality in the 80 plus years population following EGS. Methods Using our institutional 2008-2018 EGS Database, all the 80 plus years patients undergoing EGS were identified. The data were linked to the Social Security Death Index to determine cumulative mortality rates up to 3 years after discharge. Univariate and multivariable logistic regression analyses were used to determine predictors of in-hospital and 1-year cumulative mortality. Results A total of 385 patients were included with a mean age of 84 years; 54% were female. The two most common comorbidities were hypertension (76.1%) and cardiovascular disease (40.5%). The most common procedures performed were colectomy (20.0%), small bowel resection (18.2%), and exploratory laparotomy for other procedures (15.3%; e.g., internal hernia, perforated peptic ulcer). The overall in-hospital mortality was 18.7%. Cumulative mortality rates at 1, 2, and 3 years after discharge were 34.3%, 40.5%, and 43.4%, respectively. The EGS procedure associated with the highest 1-year mortality was colectomy (49.4%). Although hypertension, renal failure, hypoalbuminemia, hyperbilirubinemia, and elevated liver enzymes predicted in-hospital mortality, the only independent predictors of cumulative 1-year mortality were hypoalbuminemia (odds ratio, 2.17; 95% confidence interval, 1.10-4.27; p = 0.025) and elevated serum glutamic pyruvic transaminase (SGOT) level (odds ratio, 2.56; 95% confidence interval, 1.09-4.70; p = 0.029) at initial presentation. Patients with both factors had a cumulative 1-year mortality rate of 75.0%. Conclusion More than half of the very elderly patients undergoing major EGS were still alive at 3 years postdischarge. The combination of hypoalbuminemia and elevated liver enzymes predicted the highest 1-year mortality. Such information can prove useful for patient and family counseling preoperatively. Level of evidence Prognostic, Level III.

The objective of this study was to describe and compare the timing of cervical spine clearance in trauma patients with an unreliable physical examination. We prospectively included adult trauma patients admitted with a cervical collar and an unreliable clinical examination (as defined by the NEXUS criteria) at two level 1 trauma centers: one in the USA (US) and one in Denmark (DK). We excluded patients with cervical spine injuries requiring a collar or surgery as treatment and patients with a collar placed after hospital arrival. The primary outcome was time from emergency department (ED) arrival to collar removal. Secondary outcomes included time to CT of the cervical spine (CTCS). At the US trauma center, an institutional protocol allowing cervical spine clearance exclusively by CTCS was in place. At the Danish trauma center, cervical spine clearance was based on a clinical evaluation by an orthopedic surgeon, usually after CTCS. A total of 113 patients were included (US: n = 56; DK: n = 57). The median age was 47 years, and 68% were males. The main reasons for an unreliable physical examination were a Glasgow Coma Scale score below 14 (35%), distracting injuries (26%), cervical spine tenderness (13%) and intoxication (13%). The injury severity score at the US trauma center was higher than at the DK trauma center (median: 17 vs. 11, p = 0.03). Both time to CTCS (median: 41 vs. 18 min, p

Background The long-term consequences of in-hospital complications remain largely unknown. We sought to study the effect of complications on the long-term functional outcome of trauma patients. Methods Patients with an Injury Severity Score ≥ 9 admitted to 3, level I trauma centers between 2015 and 2017 were contacted 6 to 12 months postinjury and administered a validated trauma quality-of-life survey, assessing for the presence of any functional limitation. Functional limitation was defined as the inability to perform independently one or more activities of daily living (eg, driving, walking on flat surfaces/upstairs, dressing). Medical records and the trauma registry were reviewed systematically for all patient and injury variables. The occurrence of predefined in-hospital complications (eg, pneumonia, surgical site infection) was recorded. The impact of in-hospital complications on functional limitation was assessed using multivariate logistic regression models. Results Of 1,709 patients, 1,022 completed the study. The mean age was 58 y, 56% were male, 94% had blunt trauma, and the mean Injury Severity Score was 15. A total of 168 patients (16.4%) had a minimum of 1 in-hospital complication and reported significantly more functional limitations in most activities of daily living at 6 to 12 months, compared with those without complications. In multivariable analyses adjusting for confounders, the occurrence of complications was associated with a greater likelihood of functional limitation 6 to 12 months postinjury (odds ratio = 1.82, 95% confidence interval 1.22–2.69, P = .003). Conclusion Trauma patients with in-hospital complications have a worse long-term functional outcome. In addition to prevention of primary complications, more rehabilitation resources should be made available to trauma patients who survive complications.

Recent studies suggest that obesity is a risk factor for Clostridium difficile infection, possibly due to disruptions in the intestinal microbiome composition. We hypothesized that body mass index (BMI) is associated with increased incidence of C. difficile infection in surgical patients.In this nationwide retrospective cohort study in 680 American College of Surgeons National Surgical Quality Improvement Program participating sites across the United States, the occurrence of C. difficile infection within 30 days postoperatively between different BMI groups was compared. All American College of Surgeons National Surgical Quality Improvement Program patients between 2015 and 2016 were classified as underweight, normal-weight, overweight, or obese class I-III if their BMI was less than 18.5, 18.5 to 25, 25 to 30, 30 to 35, 35 to 40 or greater than 40, respectively.A total of 1,426,807 patients were included; median age was 58 years, 43.4% were male, and 82.9% were white. The postoperative incidence of C. difficile infection was 0.42% overall: 1.11%, 0.56%, 0.39%, 0.35%, 0.33% and 0.36% from the lowest to the highest BMI group, respectively (p0.001 for trend). In univariate then multivariable logistic regression analyses, adjusting for patient demographics (e.g., age, sex), comorbidities (e.g., diabetes, systemic sepsis, immunosuppression), preoperative laboratory values (e.g., albumin, white blood cell count), procedure complexity (work relative unit as a proxy) and procedure characteristics (e.g., emergency, type of surgery [general, vascular, other]), compared with patients with normal BMI, high BMI was inversely and incrementally correlated with the postoperative occurrence of C. difficile infection. The underweight were at increased risk (odds ratio, 1.15 [1.00-1.32]) while the class III obese were at the lowest risk (odds ratio, 0.73 [0.65-0.81]).In this nationwide retrospective cohort study, obesity is independently and in a stepwise fashion associated with a decreased risk of postoperative C. difficile infection. Further studies are warranted to explore the potential and unexpected association.Prognostic/Epidemiologic, Level IV.

Spontaneous retroperitoneal and rectus sheath hemorrhage (SRRSH) is associated with high mortality in the literature, but studies on the subject are lacking. The objective of this study was to identify early predictors of the need for angiographic or surgical intervention (ASI) in patients with SRRSH and define risk factors for mortality. We conducted a retrospective cohort study at a tertiary academic hospital. All patients with computed tomography-identified SRRSH between 2012 to 2017 were included. Exclusion criteria were age below 18 years, possible mechanical cause of SRRSH, aortic aneurysm rupture or dissection, and traumatic or iatrogenic sources of SRRSH. The primary outcome was the incidence of ASI and/or mortality. Of 100 patients included (median age 70 years, 52% males), 33% were transferred from another hospital, 82% patients were on therapeutic anticoagulation, and 90% had serious comorbidities. Overall mortality was 22%, but SRRSH-related mortality was only 6%. Sixteen patients underwent angiographic intervention (n = 10), surgical intervention (n = 5), or both (n = 1). Flank pain (OR 4.15, 95% CI 1.21–14.16, p = 0.023) and intravenous contrast extravasation (OR 3.89, 95% CI 1.23–12.27, p = 0.020) were independent predictors of ASI. Transfer from another hospital (OR 3.72, 95% CI 1.30–10.70, p = 0.015), age above 70 years (OR 4.24, 95% CI 1.25–14.32, p = 0.020), and systolic blood pressure below 110 mmHg at the time of diagnosis (OR 4.59, 95% CI 1.19–17.68, p = 0.027) were independent predictors of mortality. SRRSH is associated with high mortality but is typically not the direct cause. Most SRRSHs are self-limited and require no intervention. Pattern identification of ASI is hard.

Older adults with disease and disability are particularly vulnerable to experiencing more severe consequences of depression. The purpose of the present study is to investigate the relationship between disease comorbidities (number of disease: ND0, 1 disease: ND1 and 2 or more diseases: ND &ge, 2), hand grip strength (low HGS and high HGS), and the prevalence of depression in Korean older adults. Data from the living profiles of older people survey that was conducted by the ministry of health and welfare in Korea were utilized. Data for 6107 females and 4347 males were appropriate for statistical tests. The results demonstrated that depression was more prevalent as ND increased (p &lt, 0.01). In addition, HGS appeared lower as ND increased in both male (p &lt, 0.01) and female subjects (p &lt, 0.01). Furthermore, relative to ND0 and low HGS, ND0 and high HGS showed a ~65% reduction in the prevalence of depression (p &lt, 0.01). After adjusting for age, the prevalence of depression was reduced by ~60% in the subgroup with ND0 and high HGS relative to ND0 and low HGS (p &lt, 0.01). These data demonstrate that muscular strength indices such as HGS may be useful when assessing depression in older adults. Further research in this area is warranted.

Background Obesity has long been considered a risk factor for postoperative adverse events in surgery. We sought to study the impact of body mass index (BMI) on the clinical outcomes of the high-risk emergency general surgery (EGS) elderly patients. Methods All EGS ≥65 years old patients in the 2007-2016 ACS-NSQIP database, identified using the variables ‘emergency’ and ‘surgspec,’ were included. Patients were classified into five groups: normal weight: BMI Results A total of 78,704 patients were included, of which 26,011 were overweight (33.1%), 13,897 (17.6%) had Class I obesity, 5904 (7.5%) had Class II obesity, and 4490 (5.7%) had Class III obesity. On multivariable analyses, compared to the nonobese, patients who are overweight or with Class I-III obesity paradoxically had a lower risk of mortality, bleeding requiring transfusion, pneumonia, stroke and myocardial infarction (MI). Additionally, the incidence of MI and stroke decreased in a stepwise fashion as BMI progressed from overweight to severely obese (MI: OR: 0.84 [0.73-0.95], OR: 0.73 [0.62-0.86], OR: 0.66 [0.52-0.83], OR: 0.51 [0.38-0.68]; stroke: OR: 0.80 [0.65-0.99], OR: 0.79 [0.62-1.02], OR: 0.71 [0.50-1.00], OR: 0.43 [0.28-0.68]). Conclusion In our study of elderly EGS patients, overweight and obese patients had a lower risk of mortality, bleeding requiring transfusion, pneumonia, reintubation, stroke, and MI. Further studies are needed to confirm and investigate the obesity paradox in this patient population.

Laparoscopic cholecystectomy (LC) has a wide range of technical difficulty. Preoperative risk stratification is essential for adequate planning and patient counseling. We hypothesized that gallbladder wall thickness (GWT) is more objective marker than symptom duration in predicting complexity, as determined by operative time (OT), intraoperative events (IE), and postoperative complications.All adult patients who underwent LC during 2010-2018 were included. GWT, measured on imaging and on the histopathologic exam, was divided into three groups:3 mm (normal), 3-7 mm and7 mm. Univariate and multivariable analyses were performed to determine the association between GWT and 1) operative time, 2) the incidence of IE and 3) postoperative outcomes.A total of 1089 patients, subjects to LC, were included in the study. GWT was positively correlated with median OT (p 0.001), the incidence of IE (p 0.001) and median length of hospital stay (p 0.001). GWT independently predicted IE (OR = 2.1 95% CI: 1.3-3.4) and outperformed symptom duration, which was not significantly associated with any of the outcomes (p = 0.7).GWT independently predicted IE and may serve as an objective marker of LC complexity.

The impact of immunosuppression on the outcomes of emergent surgery remains poorly described. We aimed to quantify the impact of chronic immunosuppression on outcomes of patients undergoing emergent colectomy (EC). The Colectomy-Targeted ACS-NSQIP database 2012–2016 was queried for patients who underwent colectomy for an emergent indication. As per NSQIP, chronic immunosuppression was defined as the use of corticosteroid or immunosuppressant medication within the prior 30 days. Patients undergoing EC for any indication were divided into two groups: immunosuppressant use (IMS) and no immunosuppressant use (NIS). Patients were propensity-score-matched on demographics, comorbidities, preoperative laboratory values, and operative variables in a 1:1 ratio to control for confounding factors. The primary outcome was 30-day mortality. Secondary outcomes included overall 30-day morbidity, individual postoperative complications (e.g., wound dehiscence, anastomotic leak, and sepsis), and hospital length of stay. Out of a total of 130,963 patients, 17,707 patients underwent an EC, of which 15,422 were NIS and 2285 were IMS. Totally, 2882 patients were matched (1441 NIS; 1441 IMS). The median age was 66 [IQR 56–76]; 56.8% were female; patients more frequently underwent a diversion procedure rather than primary anastomosis (68.4% vs 31.6%). Overall, as compared to NIS, IMS patients had higher 30-day mortality (21.4% vs 18.5%, p = 0.045) and overall morbidity (79.7% vs 75.7%, p = 0.011). Particularly, IMS patients had increased rates of unplanned intubations (11.5% vs 7.9%, p = 0.001), wound dehiscence (5.7% vs 3.5%, p = 0.006), progressive renal insufficiency 2.2% vs 1.2%, p = 0.042), pneumonia (12.6% vs 10.0%, p = 0.029), and longer median hospital length of stay [12.0 (8.0–21.0) vs 11.0 (7.0–19.0), p

BACKGROUND Supplemental oxygen is recommended during the initial treatment of trauma patients according to several guidelines, but the supporting evidence is sparse. We aimed to describe the use of supplemental oxygen and occurrence of hyperoxemia in the initial phase of trauma management at two level 1 trauma centers, TC1 and TC2. METHODS In this prospective, observational study we included trauma patients ≥16 years of age. Data on pre- and in-hospital supplemental oxygen, arterial oxygen tension (PaO2 ), and outcomes (in-hospital mortality, hospital- and intensive care unit length of stay) were collected. RESULTS We included 56 patients. There were 22 (39%) females with a mean age of 49 years (SD: 18) and a median Injury Severity Score of 9 (IQR: 4-14, n = 49). A total of 23 (45%) out of 51 spontaneously breathing patients received pre-hospital supplemental oxygen, but did not differ significantly from the patients that did not receive supplemental oxygen. In-hospital, 29 (59%) out of 49 spontaneously breathing patients received supplemental oxygen. The median PaO2 was 26.5 kPa [IQR: 22.2-34.1] in four intubated patients and 12.3 kPa [IQR: 9.7-25.7] in eight patients with spontaneous respiration on supplemental oxygen. At TC1 a significantly greater proportion of spontaneously breathing patients received both pre-hospital (TC1: 18 [64%]; TC2: 5 [21%], P = 0.002) and in-hospital (TC1: 24 [92%]; TC2: 7 [30%], P

The decision to emergently operate on nonagenarian patients (NONAs) can be complex due to the uncertainty about outcomes and goals of care at this advanced age. We sought to study: (1) the outcomes and predictors of mortality for NONAs undergoing emergency general surgery (EGS) and (2) the accuracy of ACS-NSQIP mortality risk calculator in this special population.Using the 2007 to 2015 ACS-NSQIP database, we included all patients older than 90 years of age who underwent an emergent operation with a Current Procedural Terminology (CPT) code for "digestive system." Multivariable logistic regression analyses were performed to identify independent predictors of 30-day mortality. NONAs' mortality rates for different combinations of risk factors were also studied and compared to the ACS-NSQIP calculator-predicted mortality rates.Out of a total of 4,456,809 patients, 4,724 NONAs were included. The overall 30-day patient mortality and morbidity rates were 21% and 45%, respectively. In multivariable analyses, several independent predictors of 30-day mortality were identified, including recent history of weight loss, history of steroid use, smoking, functional dependence, hypoalbuminemia and sepsis or septic shock. The mortality among NONAs with a history of steroid use and a recent history of weight loss was 100%. Similarly, the mortality of NONAs with recent history of weight loss who presented with preoperative septic shock was 93%. The ACS-NSQIP calculator significantly and consistently underestimated the risk of mortality in all NONAs undergoing EGS.Most NONAs undergoing EGS survive the hospital stay and the first 30 postoperative days, even in the presence of significant preexisting comorbidities. However, the combination of recent weight loss with either steroid use or septic shock nearly ensures mortality and should be used in the discussions with patients and families before a decision to operate is made. The ACS-NSQIP surgical risk calculator should be used with caution in these high-risk patients.Prognostic study, level III.

The Emergency Surgery Score (ESS) was validated recently as an accurate and user-friendly post-operative mortality risk calculator specific for Emergency General Surgery (EGS). ESS is calculated by adding one to three integer points for each of 22 pre-operative variables (demographics, co-morbidities, and pre-operative laboratory values); increasing scores accurately and gradually predict higher mortality rates. We sought to evaluate whether ESS can predict the occurrence of post-operative infectious complications in EGS patients.Using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database from 2007-2015, all EGS patients were identified by using the "emergent" ACS-NSQIP variable and a concomitant surgery Current Procedural Terminology code for "digestive system." Patients with any missing ESS variables or those who died within 72 hours from the surgical procedure were excluded. A composite variable, post-operative infection, was created and defined as the post-operative occurrence of one or more of the following: superficial, deep incisional or organ/space surgical site infection, surgical site disruption, pneumonia, sepsis, septic shock, or urinary tract infection. ESS was calculated for all included patients, and the correlation between ESS and post-operative infection was examined using c-statistics.Of a total of 4,456,809 patients, 90,412 patients were included. The mean age of the population was 56 years, 51% were female, and 70% were white; 22% developed one or more post-operative infections, most commonly sepsis/septic shock (12.2%), surgical site infection (9%), and pneumonia (5.7%). The ESS gradually and consistently predicted infectious complications; post-operative infections developed in 7%, 24%, and 49% of patients with an ESS of 1, 5, and 10, respectively. The c-statistics for overall post-operative infection, post-operative sepsis/septic shock, and pneumonia were 0.73, 0.75, and 0.80, respectively.The ESS accurately predicts the occurrence of post-operative infectious complications in EGS patients and could be used for pre-operative clinical decision-making as well as quality benchmarking of infection rates in EGS.

Background The emergency surgery score (ESS) is a preoperative risk calculator recently validated as a mortality predictor in emergency surgery (ES) patients. We sought to evaluate the utility of ESS as an ICU admission triage tool. Methods A four-step methodology was designed. First, the 2007–2015 ACS-NSQIP database was examined to identify all ES patients using the “emergent” variable and CPT codes for “digestive system”. Second, we created a composite variable called ICUneed, defined as death or the development of one or more postoperative complication warranting critical care (e.g. unplanned intubation, ventilator dependent ≥48 h, cardiac arrest, septic shock and coma ≥24 h). Third, for each patient, ESS was calculated. Fourth, the correlation between ESS and ICUneed was assessed by calculating the model c-statistics (AUROC). Results Out of a total of 4,456,809 patients, 65,989 patients were included. The mean population age was 56 years; 51% were female, and 71% were white. The overall 30-day postoperative mortality and morbidity were 8.2% and 31.7%, respectively. ESS gradually and accurately predicted ICUneed, with 1%, 40% and 98% of patients with ESS of 2, 9 and 16 requiring critical care, respectively. Only 6.2% of patients with ESS ≤7 had an ICUneed, while 97.2% of patients with ESS ≥15 had an ICUneed. The c-statistic of the predictive model was 0.90. Conclusions ESS accurately predicts the need for postoperative critical care and ICU admission. In resource-limited settings, ESS may prove useful as an ICU triage tool ensuring a prompt rescue of the clinically deteriorating patient without unnecessary and burdensome ICU admissions.

Background Diversion of unused prescription opioids is a major contributor to the current United States opioid epidemic. We aimed to study the variation of opioid prescribing in emergency surgery. Methods Between October 2016 and March 2017, all patients undergoing laparoscopic appendectomy, laparoscopic cholecystectomy, or inguinal hernia repair in the acute care surgery service of 1 academic center were included. For each patient, we systematically reviewed the electronic medical record and the prescribing pharmacy platform to identify: (1) history of opioid abuse, (2) opioid intake 3 months preoperatively, (3) number of opioid pills prescribed, (4) prescription of nonopioid pain medications (eg, acetaminophen, ibuprofen), and (5) the need for opioid prescription refills. The mean and range of opioid pills prescribed, as well as their oral morphine equivalent, were calculated. Results A total of 255 patients were included (43.5% laparoscopic appendectomy, 44.3% laparoscopic cholecystectomy, and 12.1% inguinal hernia repair). The mean age was 47.5 years, 52.1% were female, 11.4% had a history of opioid use, and 92.5% received opioid prescriptions upon hospital discharge. Only 70.9% of patients were instructed to use nonopioid pain medications. The mean and range of opioid pills prescribed were 17.4; 0–56 (laparoscopic appendectomy), 17.1; 0–75 (laparoscopic cholecystectomy), and 20.9; 0–50 (inguinal hernia repair), while the range of prescribed oral morphine equivalent was 0–600 mg for laparoscopic appendectomy/laparoscopic cholecystectomy and 0–375 mg for inguinal hernia repair. No patients required any opioid medication refills. Conclusion Even within the same surgical service, wide variation of opioid prescription was observed. Guidelines that standardize pain management may help prevent opioid overprescribing.

Background We aimed to determine the incidence, risk factors, and outcomes of cervical spinal cord injury (CSCI) after blunt assault. Methods The ACS National Trauma Data Bank (NTDB) 2012 Research Data Set was used to identify victims of blunt assault using the ICD-9 E-codes 960.0, 968.2, 973. ICD-9 codes 805.00, 839.00, 806.00, 952.00 identified cervical vertebral fractures/dislocations and CSCI. Multivariable analyses were performed to identify independent predictors of CSCI. Results 14,835 (2%) out of 833,311 NTDB cases were blunt assault victims and thus included. 217 (1%) had cervical vertebral fracture/dislocation without CSCI; 57 (0.4%) had CSCI. Age ≥55 years was independently predictive of CSCI; assault by striking/thrown object, facial fracture, and intracranial injury predicted the absence of CSCI. 25 (0.02%) patients with CSCI underwent cervical spinal fusion. Conclusions CSCI is rare after blunt assault. While the odds of CSCI increase with age, facial fracture or intracranial injury predicts the absence of CSCI. Summary The incidence, risk factors, and outcomes of cervical spinal cord injury (CSCI) after blunt assault was investigated. 14,835 blunt assault victims were identified; 217 had cervical vertebral fracture/dislocation without CSCI; 57 had CSCI. Age ≥55 years was found to independently predict CSCI, while assault by striking/thrown object, facial fracture, and intracranial injury predicted the absence of CSCI.

Kawasaki disease (KD) is the most common cause of acquired heart disease in children. Intravenous immunoglobulin (IVIG) is the standard therapy for KD, but more than 10% of KD patients do not respond to IVIG and are at high risk for the development of coronary artery lesions (CALs). To identify clinical and genetic risk factors associated with CAL development and IVIG nonresponsiveness, this study analyzed the clinical data for 478 Korean KD patients. Multivariate logistic regression analysis showed that incomplete KD, IVIG nonresponse, fever duration of 7 days or longer, and the CC/AC genotypes of the rs7604693 single nucleotide polymorphism (SNP) in the PELI1 gene were significantly associated with the development of CALs, with odds ratios (ORs) ranging from 2.06 to 3.04. The risk of CAL formation was synergistically increased by the addition of individual risk factors, particularly the genetic variant in the PELI1 gene. Multivariate analysis also showed that a serum albumin level of 3.6 g/dl or lower was significantly associated with nonresponsiveness to IVIG [OR, 2.76; 95% confidence interval (CI), 1.34-5.68; P = 0.006]. Conclusively, incomplete KD, IVIG nonresponsiveness, long febrile days, and the rs7604693 genetic variant in the PELI1 gene are major risk factors for the development of CALs, whereas low serum albumin concentration is an independent risk factor for IVIG nonresponsiveness.

Kawasaki disease (KD) is an acute self-limited vasculitis of infants and children that manifests as fever and signs of mucocutaneous inflammation. Coronary artery aneurysms develop in approximately 15-25% of untreated children. Although the etiology of KD is largely unknown, epidemiologic data suggest the importance of genetic factors in the susceptibility to KD. In order to identify genetic variants that influence KD susceptibility, we performed a genome-wide association study (GWAS) using Affymetrix SNP array 6.0 in 186 Korean KD patients and 600 healthy controls; 18 and 26 genomic regions with one or more sequence variants were associated with KD and KD with coronary artery lesions (CALs), respectively (p

Kawasaki disease (KD) is often complicated by coronary artery lesions (CALs), including aneurysms. Because of the complications associated with KD, this disorder is the leading cause of acquired heart disease in children from developed countries. To identify genetic loci that confer a higher risk of developing CALs, we performed a case-control association study using previous genome-wide association study data for samples from KD cases only (n=186) by grouping KD patients without CALs (control: n=123) vs KD patients with extremely large aneurysms (diameter5 mm) (case: n=17). Twelve loci with one or more sequence variants were found to be significantly associated with CALs (P1 × 10(-5)). Of these, an SNP (rs17136627) in the potassium intermediate/small conductance calcium-activated channel, subfamily N, member 2 (KCNN2) at 5q22.3 was validated in 32 KD patients with large aneurysms (diameter5 mm) and 191 KD patients without CALs (odds ratio (OR)=12.6, P(combined)=1.96 × 10(-8)). This result indicates that the KCNN2 gene can have an important role in the development of coronary artery aneurysms in KD.

High-dose intravenous immunoglobulin (IVIG) therapy is the highly effective and standard treatment for Kawasaki disease (KD). However, ~20 % of KD patients have persistent fever or recurrence of fever after the initial IVIG treatment, which increases the risk for coronary artery lesions (CALs). Furthermore, the mechanism of IVIG resistance in KD patients still is unknown. The number of CC chemokine ligand 3-like 1 (CCL3L1) gene copies is reported to be associated with KD and IVIG resistance in Japanese patients. In addition, the authors observed significant upregulation of the CCL3L1 gene expression after in vitro immunoglobulin treatment in B cell lines derived from KD patients. Therefore, this study of 459 KD patients and 496 healthy control subjects tested whether the number of CCL3L1 gene copies is associated with a risk of KD, CALs, and/or IVIG resistance in Korean KD patients. However, the number of CCL3L1 gene copies was not associated with KD (P = 0.18), CAL formation (P = 0.062), or the IVIG resistance (P = 0.90). Therefore, the results indicate that the number of CCL3L1 gene copies does not have a role in susceptibility to KD or CALs nor with IVIG resistance in Korean KD patients.