Intestinal Rehabilitation Program for Adult Patients with Intestinal Failure: A 20-Year Analysis of Outcomes in the Single-Center Experience at a Tertiary Hospital.

BACKGROUND & AIMS: The intestinal rehabilitation program (IRP) is a specialized approach to managing patients with intestinal failure (IF). The goal of IRP is to reduce the patient's dependence on parenteral nutrition by optimizing nutrition intake while minimizing the risk of complications and providing individualized medical and surgical treatment. We aimed to provide a thorough overview of our extensive history in adult IRP. METHODS: We reviewed the medical records of adults with IF treated at our center's IRP over the past two decades. We collected data on demographic and clinical results, such as the causes of IF, the current status of the remaining bowel, nutritional support, and complications or mortality related to IF or prolonged parenteral nutrition. RESULTS: We analyzed a total of 47 adult patients with a median follow-up of 6.7 years. The most common cause of IF was massive bowel resection due to mesenteric vessel thrombosis (38.3%). Twenty-eight patients underwent rehabilitative surgery, including 12 intestinal transplants. The 5-year survival rate was 81.9% with 13 patients who expired due to sepsis, liver failure, or complication after transplantation. Of the remaining 34 patients, 18 were successfully weaned off from parenteral nutrition. CONCLUSION: Our results of IRP over two decades suggest that the individualized and multidisciplinary program for adult IF is a promising approach for improving patient outcomes and achieving nutritional autonomy.

Cytokine engineered NK-92 therapy to improve persistence and anti-tumor activity.

Natural killer (NK) cells are an attractive cell source in cancer immunotherapy due to their potent antitumor ability and promising safety for allogenic applications. However, the clinical outcome of NK cell therapy has been limited due to poor persistence and loss of activity in the cytokine-deficient tumor microenvironment. Benefits from exogenous administration of soluble interleukin-2 (IL-2) to stimulate the activity of NK cells have not been significant due to cytokine consumption and activation of other immune cells, compromising both efficacy and safety. Methods: To overcome these drawbacks, we developed a novel membrane-bound protein (MBP) technology to express IL-2 on the surface of NK-92 cells (MBP NK) inducing autocrine signal for proliferation without IL-2 supplementation. Results: The MBP NK cells exhibited not only improved proliferation in IL-2 deficient conditions but also stronger secretion of cytolytic granules leading to enhanced anti-tumor activity both in vitro and in vivo. Furthermore, the experiment with a spheroid solid tumor model exhibited enhanced infiltration by MBP NK cells creating higher local effector-to-target ratio for efficient tumor killing. These results suggest MBP technology can be an effective utility for NK-92 cell engineering to increase anti-tumor activity and reduce potential adverse effects, providing a higher therapeutic index in clinical applications.

Using acellular porcine dermal matrix (XCM Biologic® Tissue Matrix) to repair a giant omphalocele: A case report.

RATIONALE: An omphalocele is an abdominal wall birth defect, and a giant omphalocele (GO) is defined as an omphalocele having a diameter >5 cm or containing a herniated liver. GOs are usually treated in stages and in this case, during the silo reduction, dehiscence occurred at the suture site of the axis ring and skin edge, which was repaired using synthetic absorbable mesh. PATIENT CONCERNS: A girl infant was born at 36 weeks with a GO of 8 cm diameter, and herniated multiple organs such as the small bowel, cecum, appendix, and the entire liver. Even after the staged repair technique for the GO silo, wound dehiscence between the ring of the silo and the edge of the skin occurred and gradual reduction failed. DIAGNOSIS: A GO of 8 cm diameter, which was found during prenatal ultrasonography. INTERVENTIONS: Revision was performed to repair the defect. The small bowel and liver were still prolapsed, and there were severe adhesions. After adhesiolysis, the muscle layer of the abdominal wall was repaired using the tissue matrix, but the skin could not be repaired. After the second operation, the defect wound was dressed as sterilely as possible. OUTCOMES: The abdominal wall defect was repaired completely; there were no residual complications. LESSONS: Repair of GOs using an acellular porcine dermal matrix can be considered a viable treatment option.

Comparison of the UEscope Video Laryngoscope with the Traditional Direct Laryngoscope in Neonates and Infants: A Randomized Clinical Trial.

The role of video laryngoscopy in adults is well established, but its role in children is still inconclusive. Previous studies on the UEscope in pediatric patients with difficult airways showed that it could reduce the time to intubation (TTI) compared to a conventional direct laryngoscope. The main objective of the current study was to investigate if the use of the UEscope could reduce the TTI in neonates and infants. Forty patients under 12 months old were recruited from a single tertiary hospital from March 2020 to September 2021 and were randomly assigned to the direct laryngoscope group (n = 19, neonates = 4, infants = 15) or UEscope group (n = 21, neonates = 6, infants = 15). Although the quality of glottic view was comparable in both groups, the TTI was significantly lower in the UEscope group in both the "intention-to-treat" (-19.34 s, 95% confidence interval = -28.82 to -1.75, p = 0.0144) and "as treated" (-11.24 s, 95% confidence interval: -21.73 to 0, p = 0.0488) analyses. The UEscope may be a better choice for tracheal intubation than conventional direct laryngoscope in neonates and infants.

Endotracheal intubation in rabbits using a video laryngoscope with a modified blade.

Rabbits are being increasingly used as companion animals, and in research; thus, the need for proper veterinary care for rabbits has increased. Surgical access is more challenging in rabbits under inhalation anesthesia compared to other animals, such as dogs and cats. Rabbits have a very narrow and deep oral cavity, large incisors, and a large tongue. Moreover, their temporomandibular joint has limited mobility, making it more difficult to approach the larynx. Various methods have been proposed to overcome this difficulty. The video laryngoscope was introduced in 1999 and is useful when airway intubation is unsuccessful using a conventional laryngoscope. We postulated that a video laryngoscope with a modified size 1 Macintosh blade (McGrath MAC Video Laryngoscope, Medtronic, USA) would facilitate the intubation of New Zealand White rabbits. Sixteen specific-pathogen-free male New Zealand White rabbits weighing 3.45-4.70 kg were studied. All rabbits were intubated using the video laryngoscope. Typically, a 3.0 mm endotracheal tube was used for rabbits weighing < 4 kg, while a 3.5 mm tube was used in those weighing > 4 kg. During surgery, anesthesia was well maintained, and there were no major abnormalities in the animals' conditions. No rabbit developed breathing difficulties or anorexia after recovering from anesthesia. We established an intubation method using a video laryngoscope with a modified blade and stylet in the supine (ventrodorsal) position and successfully applied it in 16 rabbits. It is useful for training novices and for treating rabbits in veterinary hospitals with few staff members and animal research facilities where there are insufficient human resources.

Adrenocortical carcinoma and a sporadic MEN1 mutation in a 3-year-old girl: a case report.

Childhood adrenocortical carcinoma (ACC) is a rare disease that is mostly linked to familial cancer syndrome. Although the prevalence of ACC is extremely low in children, it is clinically important to diagnose ACC early because age and tumor stage are closely related to prognosis. From this perspective, understanding the underlying genetics and possible symptoms of ACC is crucial in managing ACC with familial cancer syndromes. In this report, we present the case of a 3-year-old girl who initially presented with symptoms of precocious puberty and was later found to have ACC by imaging analysis. On genetic analysis, the patient was found to have a MEN1 gene mutation. MEN1 mutations are found in patients with multiple endocrine neoplasia type 1 (MEN1), usually precipitating multiple endocrine tumors, including pituitary adenoma, parathyroid hyperplasia, and adrenal tumors. Although MEN1 mutation is usually inherited in an autosomal dominant manner, neither of the patient's parents had the same mutation, making hers a case of sporadic MEN1 mutation with initial presentation of ACC. The clinical course and further investigations of this patient are discussed in detail in this report.

Communicating multiple tubular enteric duplication with toxic megacolon in an infant: A case report.

RATIONALE: Gastrointestinal tract duplication is a rare congenial anomaly which can be found anywhere along the gastrointestinal tract. While many patients are incidentally diagnosed during operation, in some cases it can present with severe gastrointestinal symptoms. In this case report, the patient presented with signs of toxic megacolon leading to rapid aggravation of inflammatory shock. PATIENT CONCERNS: A 49-day old male infant presented with fever, poor feeding, and severe abdominal distension. DIAGNOSIS: Abdominal ultrasonography was done. During the examination, a foley catheter was inserted through the anus to evaluate bowel patency and enable rectal decompression. The tip of the foley catheter was located in a separate narrower tubular lumen adjacent to the distended rectum. These findings suggested possibility of a tubular duplication cyst of the rectum as the culprit for the bowel obstruction. INTERVENTIONS: The patient underwent emergency laparotomy. Findings showed multiple tubular intestinal duplications involving the ileum, appendix, cecum, descending colon, sigmoid colon and rectum. The true lumen of the rectosigmoid colon was completely collapsed while the adjacent tubular cyst remained severely distended and stool passage was not possible. Decompression of the sigmoid colon was done with loop colostomy with both the wall of the true bowel and enteric cyst forming the colostomy orifice. OUTCOMES: After 40 days of postoperative care, the patient was discharged with no immediate complications. Four months after the initial operation, colostomy take-down and transanal rectal common wall division was done. No complications were observed. LESSONS: To our knowledge, this is the first case to be reported where a rare presentation of intestinal duplication resulted in an acute presentation toxic megacolon. Such emergency cases can be effectively treated with emergency surgical bowel decompression and elective common wall division.

Comparison of total midgut volvulus and segmental volvulus in neonates.

BACKGROUND: Intestinal volvulus in a neonate, complete or segmental, is a true surgical emergency, which when the diagnosis is delayed can bring detrimental results. The aim of this study was to describe the clinical characteristics of intestinal volvulus during the neonatal period by comparing total midgut volvulus (TMV) and segmental volvulus (SV). METHODS: The medical records of 44 neonates who were operated on for intestinal volvulus from 1993 to 2019 were retrospectively reviewed. The patients were divided into TMV and SV groups, and clinical features were compared. RESULTS: Operations were performed on 27 patients for TMV and 17 for SV. All cases of TMV were associated with intestinal malrotation, while those with SV were not. Gestational age, birth weight, and ratio of prematurity showed no differences between the groups. Preoperative diagnosis of TMV or SV was possible in 23 and 5 (85% and 29%) cases, respectively. Intestinal resection was required in 16/17 patients (94%) with SV, while it was required in 5/27 (19%) patients with TMV. When bowel resection was performed in TMV, all but one patient suffered from short bowel syndrome leading to two mortalities, while SV group showed good recovery. CONCLUSION: Diagnosis of SV before laparotomy can be difficult. Even though performing intestinal resection in SV neonates is highly likely, it shows a favorable outcome. TMV neonates are less likely to undergo intestinal resection; however, when bowel ischemia is present, significant morbidity can occur. TYPE OF STUDY: Treatment study. LEVEL OF EVIDENCE: Level IV.

The analysis of risk for peptic ulcer disease using Korean national health and nutrition examination survey: a cross-sectional analysis of a national survey sample.

BACKGROUND: To evaluate the risk factors associated with the incidence of peptic ulcer disease (PUD), study was conducted to assess the relationship between socioeconomic and environmental factors and PUD in a large scales data of the Korean population using the Korea National Health and Nutrition Examination Survey (KNHANES). METHODS: We conducted a cross sectional study of 12,095 enrollment in the Health Professionals Follow-Up Study. The data was collected from KNHANES between 2008 and 2009 by the Division of Chronic Disease Surveillance under the Korea Centers for Disease Control and Prevention and the Korean Ministry of Health and Welfare. Multiple logistic regression analyses were used to assess the associations of PUD with the multiple variables. RESULTS: An association between old age, mental and psychosocial factor and PUD could be seen in both genders under multivariate analysis. Additionally, PUD in male associated with lower BMI and lesser exercise in life. CONCLUSIONS: These findings suggest that, in Korean, mental health is associated with increased prevalence of PUD.

Multi-layered Free-form 3D Cell-printed Tubular Construct with Decellularized Inner and Outer Esophageal Tissue-derived Bioinks.

The incidences of various esophageal diseases (e.g., congenital esophageal stenosis, tracheoesophageal fistula, esophageal atresia, esophageal cancer) are increasing, but esophageal tissue is difficult to be recovered because of its weak regenerative capability. There are no commercialized off-the-shelf alternatives to current esophageal reconstruction and regeneration methods. Surgeons usually use ectopic conduit tissues including stomach and intestine, presumably inducing donor site morbidity and severe complications. To date, polymer-based esophageal substitutes have been studied as an alternative. However, the fabrication techniques are nearly limited to creating only cylindrical outer shapes with the help of additional apparatus (e.g., mandrels for electrospinning) and are unable to recapitulate multi-layered characteristic or complex-shaped inner architectures. 3D bioprinting is known as a suitable method to fabricate complex free-form tubular structures with desired pore characteristic. In this study, we developed a extrusion-based 3D printing technique to control the size and the shape of the pore in a single extrusion process, so that the fabricated structure has a higher flexibility than that fabricated in the conventional process. Based on this suggested technique, we developed a bioprinted 3D esophageal structure with multi-layered features and converged with biochemical microenvironmental cues of esophageal tissue by using decellularizedbioinks from mucosal and muscular layers of native esophageal tissues. The two types of esophageal tissue derived-decellularized extracellular matrix bioinks can mimic the inherent components and composition of original tissues with layer specificity. This structure can be applied to full-thickness circumferential esophageal defects and esophageal regeneration.

Non-invasive optical control of endogenous Ca2+ channels in awake mice.

Optogenetic approaches for controlling Ca2+ channels provide powerful means for modulating diverse Ca2+-specific biological events in space and time. However, blue light-responsive photoreceptors are, in principle, considered inadequate for deep tissue stimulation unless accompanied by optic fiber insertion. Here, we present an ultra-light-sensitive optogenetic Ca2+ modulator, named monSTIM1 encompassing engineered cryptochrome2 for manipulating Ca2+ signaling in the brain of awake mice through non-invasive light delivery. Activation of monSTIM1 in either excitatory neurons or astrocytes of mice brain is able to induce Ca2+-dependent gene expression without any mechanical damage in the brain. Furthermore, we demonstrate that non-invasive Ca2+ modulation in neurons can be sufficiently and effectively translated into changes in behavioral phenotypes of awake mice.

Structure-based glycoengineering of interferon lambda 4 enhances its productivity and anti-viral potency.

Interferon lambda 4 (IFNλ4) has been recently known and studied for its role in hepatitis C virus (HCV) infection, but its clinical potential is significantly hampered due to its poor expression in vitro. Our study reports the successful production of IFNλ4 from a mammalian cell line through a glycoengineering and structure-based approach. We introduced de novo N-glycosylation of IFNλ4, guided by structural analysis, and produced IFNλ4 variants in Expi293F that displayed improved expression and potency. To preserve the structure and functionality of IFNλ4, the model structure of the IFNλ4 signaling complex was analyzed and the N-glycosylation candidate sites were selected. The receptor binding activity of engineered IFNλ4 variants and their receptor-mediated signaling pathway were similar to the E. coli version of IFNλ4 (eIFNλ4), while the antiviral activity and induction levels of interferon-stimulated gene (ISG) were all more robust in our variants. Our engineered IFNλ4 variants may be further developed for clinical applications and utilized in basic research to decipher the immunological roles of IFNλ4.

Pediatric Adenocarcinoma in Korea: A Multicenter Study.

PURPOSE: Adenocarcinoma is an extremely rare malignancy in the pediatric population. Research regarding pediatric adenocarcinoma is very rare in Korea. This study aimed to investigate the clinical features of pediatric adenocarcinomas of various primary organ sites in Korea. MATERIALS AND METHODS: Pediatric patients under 18 years, diagnosed with adenocarcinoma of various sites between January 1995 and December 2016, were included. We retrospectively reviewed patient and tumor characteristics and calculated survival estimates, reported as 5-year survival rate and 95% confidence interval. RESULTS: Of 80 patients (median age, 15 years; range, 10 to 17 years), 37 (46.3%) were men, and 24 (30%) had a family history of cancer or underlying disease relevant to malignancy. The cancer locations were the colon and rectum (n=32), ovaries (n=18), stomach (n=15), lung (n=4), small bowel (n=1), and other sites (n=10). Totally, 54.8% patients (42/77) had stage 3 or 4 disease. The median follow-up period was 2.0 years (range, 0 to 20.4). The 5-year overall survival estimate for all patients, and for those with stomach, colorectal, ovarian, and other cancer sites were 57.9%±11.5%, 58.2%±25.7%, 41.5%±18.2%, 87.5%±16.2%, and 64.0%±34.4%, respectively. The 5-year survival rate differed significantly between categories of adenocarcinomas into gastrointestinal (GI) (44.7%) and non-GI adenocarcinomas (78.8%) (p=0.007). The 5-year survival rate also differed significantly according to carcinoembryonic antigen level (69.3% in < 3 ng/mL, 23.8% in > 3 ng/mL; p < 0.001). CONCLUSION: In pediatric patients, adenocarcinomas arise from various organs and are often diagnosed at advanced stages. Large, prospective studies for their accurate clinical characteristics and prognostic factors are needed.

Long-Term Outcomes of Renal Function After Adult Intestinal Transplantation at a Single Small-Volume Center: 2 Cases of Renal Transplantation.

PURPOSE: Renal dysfunction more frequently occurs after intestinal transplantation (ITx) than after heart, lung, or liver transplantation. We provide a clinical analysis of renal function after adult ITx. METHODS: We retrospectively analyzed 8 adult ITx patients who survived for at least 6 months between 2004 and 2018. Glomerular filtration rate (GFR) measurements were performed at baseline, at 3 and 6 months post-transplantation, and yearly. The median follow-up duration was 53.5 months. RESULTS: All cases were isolated ITx; 3 received living-donor ITx, and 5 received deceased-donor ITx. The mean baseline GFR was 97 mL/min/1.73 m2. The GFR had decreased by more than 50% of baseline at 1 year post-transplant. Renal dysfunction was observed in 4 patients. Two patients developed acute kidney injury due to acute rejection and sepsis. One of these patients fully recovered renal function, but the second patient died. Another 2 patients developed chronic kidney disease and required hemodialysis (HD) within 6 and 3 years, respectively. The first living-donor ITx patient lost renal function progressively over 6 years after ITx. She received a renal graft from the same living donor as for the ITx after 3 years of HD. The other patient (deceased-donor ITx) received a kidney from his daughter at 5 months after HD. CONCLUSIONS: To obtain an accurate assessment of renal function, frequent direct measurements of GFR should be performed to facilitate early diagnosis of renal impairment and to determine subsequent strategies to improve renal function after ITx.

Psychometric properties of transitional care instruments and their relationships with health literacy: Brief PREPARED and Care Transitions Measure.

OBJECTIVE: To assess the psychometric properties of the Brief PREPARED (B-PREPARED) and the Care Transitions Measure (CTM) in patients discharged from hospitals in Korea, and examine their relationships with health literacy. DESIGN: A cross-sectional study with a follow-up telephone survey 4 weeks post-discharge. SETTING: Six medical and surgical wards in a tertiary hospital in Seoul. PARTICIPANTS: 293 patients discharged from general wards. MAIN OUTCOME MEASURES: Psychometric properties of the Korean versions of the B-PREPARED and the 15- and 3-item CTM (CTM-15 and CTM-3), and the 3-item Brief Screening Questionnaire for health literacy. RESULTS: All instruments discriminated well between patients who were satisfied with hospital care and the discharge process, and those who were not. One month post-discharge, the CTM-15 score was significantly higher in patients with good health status than the others, and the CTM-3 score was significantly higher in patients who used outpatient care than the others. However, no significant difference was found in the scores for all instruments by emergency department visits, rehospitalization, and medication adherence. Cronbach's alpha values were 0.69 for B-PREPARED, 0.91 for CTM-15 and 0.67 for CTM-3. Intraclass correlation coefficients were 0.64, 0.75 and 0.66, respectively. Approximately 33% of the participants had limited health literacy. After adjusting for other patient variables, those with inadequate health literacy had lower scores on all instruments. CONCLUSIONS: Although the three instruments had acceptable validity and reliability, they showed limited criterion validity. Patients with limited health literacy should be supported to ensure the quality of transitional care.

Current Status of Pediatric Critical Care in Korea: Results of 2015 National Survey.

BACKGROUND: The aim of this study was to describe the structure, organization, management, and staffing of pediatric critical care (PCC) in Korea. METHODS: We directed a questionnaire survey for all Upper Grade General Hospitals (n = 43) in Korea in 2015. The first questionnaire was mainly about structure, organization, and staffing and responses were obtained from 32 hospitals. The second questionnaire was mainly about patients and management. Responses to second questionnaire were obtained from 18 hospitals. RESULTS: Twelve from 32 Upper Grade General Hospitals had pediatric intensive care units (PICUs) and 11 of them had the PICU which was exclusive for children. Total number of PICU beds in Korea was 113. The ratio of the number of PICU beds to the number of children was 1:77,460 in Korea and this ratio is lower than that of other developed countries. The mean number of beds in the PICUs was 9.4 ± 9.3 (range, 2-30). There were 16 medical doctors who were assigned for PCC and only 5 of them were full time pediatric intensivists. In the 18 Upper Grade General Hospitals that responded to the second questionnaire survey, there were 97 patients in the PICUs with an average number of 5.7 ± 7.2 (range, 0-22) on the survey day. The mean age of the patients was 3.4 ± 5.6 years. The mean length of hospital stay was 82 ± 271 days. The mean Pediatric Risk of Mortality score III was 9.4 ± 7.8 at the time of admission to the PICUs. CONCLUSION: There is a considerable shortage of PICU beds compared to those in developed countries. In addition, the proportion of PICUs with PCC specialists is much lower than those in the US and European countries.

IFN-λ4 potently blocks IFN-α signalling by ISG15 and USP18 in hepatitis C virus infection.

Genetic polymorphisms in IFNL4 have been shown to predict responses to IFN-α-based therapy in hepatitis C virus (HCV)-infected patients. The IFNL4-ΔG genotype, which encodes functional IFN-λ4 protein, is associated with a poor treatment response. In the present study, we investigated the induction and biological effects of IFN-λ4 in HCV-infected hepatocytes and their association with responsiveness to IFN-α. We also studied the effects of direct-acting antiviral (DAA) treatment on IFN-λ4 expression and IFN-α responsiveness. HCV infection induced IFN-λ4 expression at mRNA and protein levels in primary human hepatocytes (PHHs). In hepatoma cells, IFNL4 gene transfection or recombinant IFN-λ4 protein treatment robustly increased the protein levels of ISG15 and USP18 in an IFNLR1-dependent manner and potently blocked IFN-α signalling. The ISG15/USP18-mediated IFN-α unresponsiveness was demonstrated by transfection of siRNAs targeting ISG15 and/or USP18. This potent IFN-λ4 effect was related to prolonged ISG expression after IFNL4 gene transfection. DAA treatment of HCV-infected PHHs reduced the expression of IFN-λs, including IFN-λ4, and restored IFN-α responsiveness. These results demonstrate that virus-induced IFN-λ4 potently blocks IFN-α signalling by inducing high protein levels of ISG15 and USP18. Moreover, the data clearly demonstrate that DAA therapy restores IFN-α responsiveness in HCV-infected cells.

A Comparison of Self-Inflicted Stab Wounds Versus Assault-Induced Stab Wounds.

BACKGROUND: Although self-inflicted and assault-induced knife injuries might have different mortality and morbidity rates, no studies have actually evaluated the importance of the cause of knife injuries in terms of patient outcomes and treatment strategies. OBJECTIVES: The aims of this study were to assess the difference between the outcomes of patients presenting with self-inflicted stab wounds (SISW) versus assault-induced stab wounds (AISW). PATIENTS AND METHODS: A retrospective review of the relevant electronic medical records was performed for the period between January 2000 and December 2012 for patients who were referred to the department of surgery for stab wounds by the trauma team. The patients were divided into either SISW (n = 10) or AISW groups (n = 11), depending on the cause of the injury. RESULTS: A total of 19 patients had undergone exploratory laparotomy. Of the nine patients with SISW undergoing this procedure, no injury was found in seven of the patients. In the AISW group, eight of the ten laparotomies were therapeutic. Three patients in the AISW group died during hospital admission. The average number of stab wounds was 1.2 for the SISW group and 3.5 for the AISW group. Organ injuries were more frequent in the AISW group, affecting the lung (2), diaphragm (3), liver (5), small bowel (2), colon (2), and kidney (1). CONCLUSIONS: Although evaluations of the initial vital signs and physical examinations are still important, the history regarding the source of the stab wounds (AISW vs. SISW) may be helpful in determining the appropriate treatment methods and predicting patient outcomes.

Designed nucleases for targeted genome editing.

Targeted genome-editing technology using designed nucleases has been evolving rapidly, and its applications are widely expanding in research, medicine and biotechnology. Using this genome-modifying technology, researchers can precisely and efficiently insert, remove or change specific sequences in various cultured cells, micro-organisms, animals and plants. This genome editing is based on the generation of double-strand breaks (DSBs), repair of which modifies the genome through nonhomologous end-joining (NHEJ) or homology-directed repair (HDR). In addition, designed nickase-induced generation of single-strand breaks can also lead to precise genome editing through HDR, albeit at relatively lower efficiencies than that induced by nucleases. Three kinds of designed nucleases have been used for targeted DSB formation: zinc-finger nucleases, transcription activator-like effector nucleases, and RNA-guided engineered nucleases derived from the bacterial clustered regularly interspaced short palindromic repeat (CRISPR)-Cas (CRISPR-associated) system. A growing number of researchers are using genome-editing technologies, which have become more accessible and affordable since the discovery and adaptation of CRISPR-Cas9. Here, the repair mechanism and outcomes of DSBs are reviewed and the three types of designed nucleases are discussed with the hope that such understanding will facilitate applications to genome editing.

Proper tip position of central venous catheter in pediatric patients.

BACKGROUND: In this study, we analyzed the thin-section pulmonary computed tomographic (CT) angiogram scans of pediatric patients to determine the normative length of superior vena cava (SVC) and the distance between carina and cephalad of SVC or cavocatrial junction. METHODS: Consecutive child patients, under 13 years of age in whom the central catheters were inserted under ultrasound guidance from December 2004 to April 2005 were evaluated retrospectively. RESULTS: In the 14 cases, the mean age was 7.2 ± 4.21 years. The mean length and diameter of the SVC in the pediatric patients were 45.6 ± 23.03 and 13.7 ± 3.62 mm, respectively. The distance from the carina to the cavoatrial junction was 22.0 ± 9.98 mm. The mean distance from the superior margin of the SVC to the carina was 23.7 ± 16.70 mm. The mean distance from the carina to the catheter tip was 38.9 ± 18.60 mm. In no case was the cavoatrial junction cephalad with respect to the carina. Carina to cavoatrial junction junction was significantly associated with age, height, and weight, respecitively (r = 0.750; p = 0.005, r = 0.763; p = 0.004; r = 0.777; p = 0.003). CONCLUSIONS: The carina is a good landmark for the upper border of the cavoatrial junction. Length of carina to cavoaterial juction was associated with age. The rates of malposition and re-intervention and the patient's exposure to radiation can be reduced by using ultrasound during the catheter insertion.