[Effect of SLC7A11 gene downregulation on the gefitinib resistance of lung adenocarcinoma PC9/GR cells and its mechanism].

Objective: To screen the key genes involved in gefitinib resistance of lung adenocarcinoma PC9/GR cells which harbored 19 exon mutation of epidermal growth factor receptor (EGFR) gene, and discuss the effect and mechanism of downregulation of solute carrier family 7 member 11 (SLC7A11) on the gefitinib resistance of PC9/GR cells. Methods: RNA microarray was conducted to detect the gene expressions in PC9 and PC9/GR cells. The differently expressed genes were screened by using limma package of R language and analyzed by Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis. Western blotting was performed to determine the expression of SLC7A11 protein in PC9 and PC9/GR cells. PC9/GR cells were infected with lentivirus plasmid containing short hairpin RNA (shRNA) targeting SLC7A11 or negative control shRNA (sh-NC), respectively. Real-time quantitative polymerase chain reaction (RT-qPCR) was performed to evaluate the efficacy of shRNA on the expression of SLC7A11 mRNA. Cell counting kit-8 (CCK-8) assay was conducted to determine the suppressing effect of gefitinib on PC9/GR cells. Mito-Tracker Red CMXRos probe and malondialdehyde (MDA) assay kit were used to evaluate gefitinib-induced ferroptosis in PC9/GR cells. Immunohistochemistry (IHC) was conducted to detect the expression of SLC7A11 protein in the tumor tissues of advanced stage lung adenocarcinoma patients harboring 19 exon mutation of EGFR gene. Thirty-six advanced stage lung adenocarcinoma patients who received EGFR-tyrosihe kinase inhibitor(TKI) as first-line treatment in Fourth Hospital of Hebei Medical Unviersity were enrolled. Kaplan-Meier survival curve was drawn to analyze the correlation between SLC7A11 expression and progression-free survival (PFS) of the patients. Results: RNA array demonstrated that 2 888 genes were differently expressed between PC9 and PC9/GR cells. KEGG analysis showed that ferroptosis-related gene was one of the most enriched region of the differently expressed genes between PC9 and PC9/GR cells. These ferroptosis-related gene cohort contained 13 genes, among which SLC7A11 exhibited the most significant difference. Western blotting showed that the expression of SLC7A11 protein in PC9/GR cells was significantly higher than that in PC9 cells (0.76±0.03 vs. 0.19±0.02, P<0.001). The 50% inhibiting concentration (IC(50)) of gefitinib was 35.08 µmol/L and 64.01 µmol/L for sh-SLC7A11 and sh-NC group PC9/GR cells, respectively. PC9/GR cells in sh-SLC7A11 group exhibited significantly lower density of mitochondria fluorescence after gefitinib treatment, compared to the sh-NC group (213.77±26.50 vs. 47.88±4.55, P<0.001). In addition, PC9/GR cells in sh-SLC7A11 group exhibited significantly higher MDA after gefitinib treatment, compared to the sh-NC group [(15.43±1.60) µmol/mg vs. (82.18±7.77) µmol/mg, P<0.001]. The PFS of the patients with low expression of SLC7A11 (n=18) was significantly longer than the patients with high expression of SLC7A11 (n=18, 16.77 months vs. 9.14 months, P<0.001). Conclusion: Downregulation of SLC7A11 could increase the sensitivity of PC9/GR cells to gefitinib by promoting ferroptosis.

Coagulation parameters and Apgar score are associated with severity in preterm infants.

OBJECTIVE: Coagulation parameters are used to diagnose hematological diseases. The correlation between the coagulation parameters and Apgar score at 5 min is yet to be elucidated. The present study aimed at describing the neonatal coagulation parameters in preterm infants with a low Apgar score at 5 min. PATIENTS AND METHODS: In this case-control study, 32 serious preterm infants were compared with 20 preterm infants, according to the Apgar score at 5 min. The prothrombin time (PT), thrombin time (TT), fibrinogen (Fbg), activated partial thromboplastin time (APTT), calculated international normalized ratio (INR), D-dimer (D2), fructose diphosphate sodium (FDP), and procalcitonin (PCT) values were recorded. The linear correlation between coagulation parameters and Apgar score at 5 min was analyzed by linear regression. The two groups were compared using GraphPad Prism 8 (LaJolla, CA, USA). RESULTS: In the study, the mean coagulation parameters were significantly higher in the serious preterm infants with low the Apgar score at 5 min compared to the preterm infants with normal Agar scores at 5 min (p<0.05). The correlation between coagulation parameters and Apgar score at 5 min was recorded (PT: R=0.3984; APTT: R=0.3165; INR: R=0.4139). CONCLUSIONS: The coagulation parameters were significantly higher in serious preterm infants with a low Apgar score at 5 min. Also, the coagulation parameters and Apgar score at 5 min are associated with severity in preterm infants.

Out of the labor force due to health reasons? An analysis of the Survey of Income and Program Participation regarding persons with visual impairments.

Persons with visual impairments (VI) have a high nonparticipation rate in the labor force. Information about factors influencing their labor force participation could provide insight into how to increase employment rates. We selected persons with VI from the Survey of Income and Program Participation to investigate factors that differentiate persons out of the labor force (OLF) for chronic health or disability reasons from those employed and those OLF due to other reasons. Persons with VI and OLF for chronic health or disability reasons were more likely to have additional disabilities; have physical, mental, or other health limitations to work; and receive Supplemental Security Income or Social Security Disability Insurance. Compared with those employed, people with VI and OLF for chronic health or disability reasons appear to have multiple characteristics indicating poorer health, lower education attainment, and greater financial insecurity. Compared with those OLF due to other reasons, people with VI and OLF for chronic health or disability reasons were less likely to be female but more likely to receive food assistance and to indicate disadvantaged health status. These results suggest that skills to accommodate vision disability or health conditions are essential to employment or further education, and additional education may expand vocational options. Benefits counseling, encouragement, and careful career planning may assist persons with VI in moving toward financial independence.

MiR-93 blocks STAT3 to alleviate hepatic injury after ischemia-reperfusion.

OBJECTIVE: Signal transducer and activator of transcription 3 (STAT3) is correlated with ischemia-reperfusion (I-R) injury. The previous studies showed a decreased miR-93 expression after I-R injury of heart or brain organs, but without knowledge in liver tissues. This study aims to investigate effects of MiR-93 on the hepatic injury after ischemia/reperfusion. MATERIALS AND METHODS: Rat liver I-R model was generated. Liver function indexes including alanine transaminase (ALT) and aspartate aminotransferase (AST) were quantified, and serum tumor necrosis factor α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) levels were quantified. Hepatic tissue apoptosis was measured by transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL), and expression of microRNA-93 (miR-93), STAT3, and phosphorylated STAT3 (p-STAT3) were measured. Dual luciferase reporter gene assay confirmed targeted relationship between miR-93 and STAT3. Agomir or miR-93 agomir was injected into the peritoneal cavity of I-R model, followed by ALT and AST assays. Serum levels of TNF-α, IL-1ß, and IL-6 were measured, followed by TUNEL assay for comparing STAT3 and p-STAT3 expression. RESULTS: Comparing to sham group, I-R group rat showed significantly elevated serum ALT, AST, TNF-α, IL-1ß, and IL-6 contents, along with significantly elevated hepatic cell apoptosis, plus decreased miR-93 expression, whilst STAT3 and p-STAT3 expression was enhanced. Intraperitoneal injection of miR-93 agomir significantly decreased STAT3 or p-STAT3 expression, and decreased cell apoptotic rate. Serum levels of ALT, AST, TNF-α, IL-1ß, and IL-6 were significantly decreased, accompanied by improved liver function. CONCLUSIONS: Hepatic I-R injury is accompanied by miR-93 down-regulation, plus STAT3 up-regulation. Overexpression of miR-93 significantly depressed STAT3 expression in liver I-R injury, alleviated hepatic injury or apoptosis, decreased inflammatory response, and improved liver function.

[Clinical analysis of 128 cases of cervical lesion diagnosed by multi-point biopsy of colposcopy and endocervical curettage].

Objective: To investigate the clinical values of colposcopy and cervical biopsy and/or endocervical curettage (ECC) in the diagnosis of cervical lesion. Methods: Clinical data of 128 cases of cervical lesion diagnosed by Xuzhou Cancer Hospital from January 23, 2014 to October 11, 2016 were collected and retrospectively analyzed, all patients underwent colposcopy and cervical biopsy and/or ECC. Results: Among them, the age between 30 to 50 years old were 70 cases, whose transformation zone types of Ⅰ, Ⅱ and Ⅲ were 28 cases (40.0%), 23 cases (32.9%) and 19 cases (27.1%), respectively. The age older than 50 years were 45 cases, whose transformation zone types of Ⅱ and Ⅲ were 1 case (2.2%) and 44 cases (97.8%), respectively. Among the 128 cases of cervical lesions, diagnostic results of colposcopy showed that the chronic inflammation were 57 cases, cervical intraepithelial neoplasia (CIN)Ⅰwere 35 cases, CINⅡor CINⅡ~Ⅲ were 8 cases, CIN Ⅲ were 5 cases and cervical cancer were 23 cases. Alternatively, the pathological results showed that the chronic inflammation were 81 cases, CINⅠwere 17 cases, CINⅡor CINⅡ~Ⅲ were 7 cases, CIN Ⅲ were 5 cases and cervical cancer were 18 cases, respectively. Among the 81 cases of chronic inflammation diagnosed by pathology, 52 cases (64.2%) were consistent with the diagnostic results of colposcopy. Among the 17 cases of low grade squamous epithelial cell lesion (LSIL) diagnosed by pathology, 10 cases were in agree with the diagnostic results of colposcopy. Among the 12 cases of high-grade squamous epithelial cell lesion (HSIL) diagnosed by pathology, 9 cases were concordant with the diagnostic results of colposcopy. Among the 18 cases of cervical cancer diagnosed by pathology, 17 cases were consistent with the diagnostic results of colposcopy. Conclusions: The type of transformation zone is positively correlated with the age, and it can help to choose biopsy and therapeutic manner. The diagnostic accuracies of HSIL and early stage of cervical cancer by multi-point biopsy of colposcopy and/or ECC are high. The cervical lesions which are difficultly found by direct visualization can be identified by colposcopy, and thus provides objective evidence to determine the therapeutic manner for patients with stage ⅡA of cervical cancer.

The antitumor efficacy of anti-p21Ras scFv mediated by the dual-promoter-regulated recombinant adenovirus KGHV300.

Ras mutations and overexpression of the Ras protein, p21Ras, are main causes of cancer development and progression, which has made the Ras gene and p21Ras important targets for therapy of Ras-driven cancers. We previously prepared recombinant adenovirus KGHV100 based on replication-defective adenovirus type 5, which could intracellularly express anti-p21Ras single chain fragment viable antibodies (scFv) and repress tumor growth in vitro and in vivo. However, the anti-tumor effects of this anti-p21Ras scFv were limited by short-term scFv expression due to a replication defect of KGHV100. To enhance the anti-tumor efficacy and safety of anti-p21Ras scFv, the present study constructed a dual-promoter-regulated recombinant adenovirus KGHV300 that carried anti-p21Ras scFv. In KGHV300, the expression levels of the essential replication genes E1a and E1b, were controlled by the human telomerase reverse transcriptase promoter and the hypoxia response element, respectively, and the anti-p21Ras scFv gene was controlled by the cytomegalovirus promoter. The conditional replication of KGHV300 and its antitumor efficacy were characterized in several tumor cell lines in vitro and in xenograft models of human breast cancer in nude mice. TCID50 assay demonstrated that KGHV300 could replicate in tumor cell lines but not in normal cell lines. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay indicated that the growth of tumor cells was effectively inhibited by KGHV300 infection. In MDA-MB-231 tumor xenograft models, KGHV300 effectively and significantly inhibited tumor growth and induced apoptosis of tumor cells. We concluded that the recombinant adenovirus KGHV300 may be a more potent and safer antitumor therapeutic for Ras-driven cancer biotherapy.

Harnessing the clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated Cas9 system to disrupt the hepatitis B virus.

The current therapies to treat hepatitis B virus (HBV) infection are limited. Recently, clustered regularly interspaced short palindromic repeat (CRISPR) systems, originally identified in bacteria and archaea, have been found to consist of an RNA-based adaptive immune system that degrades complimentary sequences of invading plasmids and viruses. Here, we studied the effects of the CRISPR/CRISPR-associated Cas9 system that was targeted to the surface antigen (HBsAg)-encoding region of HBV, both in a cell culture system and in vivo. The HBsAg levels in the media of the cells and in the sera of mice were analyzed by a quantitative enzyme-linked immunosorbent assay. The HBV DNA levels were assessed by quantitative PCR and HBsAg expression in mouse livers was assessed by an immunohistochemical assay. The amount of HBsAg secreted in the cell culture and mouse serum was reduced by CRISPR/Cas9 treatment. Immunohistochemistry analyses showed almost no HBsAg-positive cells in the liver tissue of CRISPR/Cas9-S1+X3-treated mice. The CRISPR/Cas9 system efficiently produced mutations in HBV DNA. Thus, CRISPR/Cas9 inhibits HBV replication and expression in vitro and in vivo and may constitute a new therapeutic strategy for HBV infection.

Complications of the endovascular management of acute ischemic stroke.

Acute ischemic stroke is a significant source of morbidity and mortality across the globe. Currently, the only US Food and Drug Administration approved medical treatment of acute ischemic stroke is intravascular (IV) alteplase. While IV thrombolysis has been shown to decrease morbidity and mortality from acute ischemic stroke, it is limited in both its efficacy in certain types of stroke, as well as in its generalizability. It has been shown that time to revascularization is one of the most important predictors of outcomes in acute ischemic stroke, and thus clinicians have turned to endovascular options in efforts to improve outcomes from stroke. Direct intra-arterial thrombolysis was one of the first of such efforts to improve efficacy rates and increase the timeline for thrombolytic therapy. More recently, investigators and clinicians have turned to newer endovascular options in attempts to further improve recanalization rates. Many different endovascular techniques have been employed and are growing exponentially in use. Examples include stenting, as well as mechanical thrombectomy with both older-generation devices and newer stent retrieval technology. While the majority of the literature focuses on the effectiveness of different techniques, such as recanalization rates and major overall outcomes such as death and disability, there is very little literature on the complications of the different techniques. The purpose of this article is to review the different forms of endovascular treatment of acute ischemic stroke and their associated complications.

Defining risks and predicting adverse events after lower extremity bypass for critical limb ischemia.

Successful treatment of patients with critical limb ischemia (CLI), hinges on the adequacy of revascularization. However, CLI is associated with a severe burden of systemic atherosclerosis, and patients often suffer from multiple cardiovascular comorbidities. Therefore, CLI patients in general represent a cohort at increased risk for procedural complications and adverse events. Although endovascular therapy represents a minimally invasive alternative to open surgical bypass, the durability of surgical reconstruction is superior, and it remains the "gold standard" approach to revascularization in CLI. Therefore, selection of the optimal treatment modality for individual patients requires careful consideration of the procedural risks and likelihood of adverse events associated with surgery. Individualized decision-making with regard to revascularization strategy requires a comprehensive understanding of the likelihood of adverse outcomes after major surgery. Here we review the risks of surgical bypass in patients with CLI, with particular emphasis on the identification of preoperative variables that predict poor outcome.

Variability in anesthetic considerations for arteriovenous fistula creation.

INTRODUCTION: Anesthetic options for arteriovenous fistula (AVF) creation include regional anesthesia (RA), general anesthesia (GA) and local anesthetic for select cases. In addition to the benefits of avoiding GA in high-risk patients, recent studies suggest that RA may increase perioperative venous dilation and improve maturation. Our objective was to assess perioperative outcomes of AVF creation with respect to anesthetic modality and identify patient-level factors associated with variation in contemporary anesthetic selection. METHODS: National Surgical Quality Improvement Project (NSQIP) data (2007-2010) were accessed to identify patients undergoing AVF creation. Univariate analysis and multivariate logistic regression were performed to assess the relationships among patient characteristics, anesthesia modality and outcome. RESULTS: Of 1,540 patients undergoing new upper extremity AVF creation, 52% were male and 81% were younger than 75 years. Anesthesia distribution was GA in 85.2%, local/monitored anesthetic care (MAC) in 2.9% and RA in 11.9% of cases. By multivariate analysis, independent predictors of RA were dyspnea at rest (hazard ratio [HR] 2.3, 95% confidence interval [CI] 1.1-4.9), age >75 (HR 1.6, 95% CI 1.1-2.3) and teaching hospital status as indicated by housestaff involvement (HR 3.7, 95% CI 2.5-5.5). RA was associated with higher total operative time, duration of anesthesia, length of time in operating room and duration of anesthesia start until surgery start (p<0.01). There were no differences between perioperative complications or mortality among anesthetic modalities, although all deaths occurred in the GA group. DISCUSSIONS: Despite recent reports highlighting potential benefits of RA for AVF creation, GA was surprisingly used in the vast majority of cases in the United States. The only comorbidities associated with preferential RA use were advanced age and dyspnea at rest. Practice environment may influence anesthetic selection for these cases, as a nonteaching environment was associated with GA use. The trend seen here toward higher mortality in GA and the potential perioperative benefits of RA for the access should encourage more widespread use of RA in practice for this high-risk patient population.

Risk factors for protracted postoperative length of stay after lower extremity bypass for critical limb ischemia.

BACKGROUND: Compared with other common chronic conditions, admissions for management of peripheral arterial disease (PAD) are associated with prolonged hospitalizations. Length of stay (LOS) is one of many metrics receiving increased attention in the current focus on efficient healthcare delivery. Our objective was to characterize LOS among patients with severe PAD, those undergoing surgical bypass for critical limb ischemia (CLI), and identify risk factors for protracted postoperative LOS. METHODS: Patient data from the 2007 to 2009 American College of Surgeons National Surgical Quality Improvement Program were used to develop a database consisting of patients undergoing bypass surgery for CLI (n = 4,894). Protracted postoperative LOS was defined as the top quartile of days hospitalized from surgery to discharge. Preoperative risk factors with significant association (Pearson chi-squared test; P < 0.05) were used to develop a logistic regression model for protracted postoperative LOS. RESULTS: Average postoperative LOS was 7.5 days (median 6 days). The top quartile of postoperative LOS, >8 days, was used to define protracted LOS. Independent preoperative risk factors for protracted postoperative LOS included demographic characteristics (advanced age and non-Caucasian race), comorbidities, and medical history (e.g., obesity, dialysis dependence, severe cardiac and pulmonary disease, and bleeding disorders). Indicators of PAD severity (e.g., distal target sites, open wounds or gangrene, and prior arterial surgery) were also independent predictors of protracted LOS after surgery. The greatest predictors of extended postoperative LOS were prolonged preoperative hospitalization (OR 2.2 [95% CI: 1.8-2.6], P < 0.001) and preoperative dependent functional status (OR 2.0 [95% CI: 1.7-2.3], P < 0.001 for partial dependence; OR 2.8 [95% CI: 1.8-4.3], P < 0.001 for totally dependent status), where OR and CI stand for odds ratio and confidence interval. CONCLUSIONS: Here, we identify preoperative risk factors for protracted postoperative LOS after infrainguinal bypass for CLI. These findings provide an important evidence basis for ongoing efforts to reduce healthcare spending and facilitate provision of efficient health care. Future efforts will include prospective identification of patients at high risk for protracted postoperative LOS and targeted multidisciplinary efforts to reduce associated costs without sacrificing healthcare quality.

Endovascular intervention for tibial artery occlusive disease in patients with critical limb ischemia.

Surgical bypass has traditionally been the gold standard for treating critical limb ischemia caused by isolated infrapopliteal arterial disease (IP CLI). However, as endovascular techniques continue to progress, they are increasingly applied to this patient population, especially to the high-risk surgical cohort or patients with limited surgical options. This enthusiasm to employ endovascular interventions in IP CLI is accompanied by persistent controversies, as demonstrated in the recent literature. Percutaneous transluminal balloon angioplasty has been the predominant endovascular intervention applied to treat IP CLI and recent literature supports its role. The durability of percutaneous transluminal balloon angioplasty is limited, and thus this intervention is recommended for high-risk patients with limited life expectancy. Bare-metal stents for IP CLI currently do not have supportive data to warrant their use as a primary treatment. Newer drug-eluting stents improve patency and prevent restenosis, but they do not significantly improve patient clinical status compared with bare-metal stents alone. Drug-coated balloons are still relatively new tools in this arena and evidence of their safety and clear efficacy are still lacking. The data on atherectomy, in all of its forms, for IP CLI are overall variable, without any clear benefit to justify its increased complication risks and costs over other modalities. Use of retrograde tibial/pedal access for treating IP CLI as a viable alternative to antegrade access and treatment from a totally retrograde approach has recently been described. Level I evidence to aid in clarifying the true efficacy for each of these endovascular modalities is greatly needed. As we await these data, we must remember that, as with any arterial intervention, proper patient selection is extremely important and the intervention, whether endovascular or open surgical repair, should be tailored to the individual patient's anatomy and disease characteristics.

Population-based estimate of the burden of acute gastrointestinal illness in Jiangsu province, China, 2010-2011.

To determine the burden and distribution of acute gastrointestinal illness (AGI) in the population, a cross-sectional, monthly face-to-face survey of 10 959 residents was conducted in Jiangsu province between July 2010 and June 2011. The adjusted monthly prevalence was 4.7% with 0.63 AGI episodes/person per year. The prevalence was the highest in children aged <5 years and lowest in persons aged ≥ 65 years. A bimodal seasonal distribution was observed with peaks in summer and winter. Regional difference of AGI prevalence was substantial [lowest 0.5% in Taicang, highest 15.1% in Xinqu (Wuxi prefecture)]. Healthcare was sought by 38.4% of the ill respondents. The use of antibiotics was reported by 65·2% of the ill respondents and 38.9% took antidiarrhoeals. In the multivariable model, gender, education, season, sentinel site and travel were significant risk factors of being a case of AGI. These results highlight the substantial burden of AGI and the risk factors associated with AGI in Jiangsu province, China.

A feasibility study for determining ablative margin with 3D-CEUS-CT/MR image fusion after radiofrequency ablation of hepatocellular carcinoma.

PURPOSE: To explore the feasibility and value of 3D-CEUS-CT/MR image fusion in evaluating ablative margin (AM) after radiofrequency ablation of hepatocellular carcinoma. METHODS AND MATERIALS: There were 49 HCC in 41 patients enrolled in our prospective study. The AM were evaluated with 3D-CEUS-CT/MR image fusion, the results were divided into two groups: in group A, the tumor was completely ablated with a 5 mm AM; in group B, the tumor was completely ablated, but a 5 mm AM was not obtained. The time used in US-CT/MR image fusion and 3 D image post-processing, the technical success rate of 3D-CEUS-CT/MR image fusion and the relation between LTP and AM were observed. RESULTS: The time taken for US-CT/MR image fusion and 3 D image post-processing was 9.2 ±â€Š2.1 min (6 - 12 min), 14.6 ±â€Š2.6 min (9 - 20 min), respectively. The technical success rate of 3D-CEUS-CT/MR image fusion was 81.6 % (40/49). 27 HCC had sufficient AM (group A) and 13 HCC had insufficient AM (group B). The LTP rates in groups A and B were 0/27 and 4/13, respectively. There was a significant difference between groups A and B (P = 0.002). There was a significant negative correlation between LTP and AM (r = -1.000, P< 0.001), and the locations of LTP and insufficient AM were concordant. CONCLUSIONS: The results suggest that 3D-CEUS-CT/MR image fusion is feasible and useful in evaluating the AM after HCC ablation.

Diagnostic, surgical judgment, and systems issues leading to reoperation: mining administrative databases.

BACKGROUND: Underreporting of surgical adverse events limits the ability to identify quality and safety issues. Automated screening of the clinical information system (CIS) can improve case capture and reduce dependency on self-reporting. We compared screening of a CIS to self-reporting for identifying unplanned reoperation and also examined the relationship between causality and probability of reporting. METHODS: Between 2005 and 2009, all unplanned reoperations identified by automated screening of databases were reviewed and classified according to causality. Comparison was made to cases self-reported to departmental morbidity and mortality; conditional probability analysis assessed the likelihood of reporting as a function of causality. RESULTS: Of 104,938 operations performed, automated CIS screening identified 1,010 cases requiring unplanned reoperation; 23.6% were self-reported to morbidity and mortality; the probability of reporting varied widely depending on causality. CONCLUSIONS: Screening of a CIS for adverse events requiring reoperation revealed significant underreporting, with additional bias in reporting based on underlying causality.