Background: Atherogenic dyslipidemia, which is frequently associated with type 2 diabetes (T2D) and insulin resistance, contributes to the development of vascular complications. Statin therapy is the primary approach to dyslipidemia management in T2D, however, the role of non-statin therapy remains unclear. Ezetimibe reduces cholesterol burden by inhibiting intestinal cholesterol absorption. Fibrates lower triglyceride levels and increase high-density lipoprotein cholesterol (HDL-C) levels via peroxisome proliferator- activated receptor alpha agonism. Therefore, when combined, these drugs effectively lower non-HDL-C levels. Despite this, few clinical trials have specifically targeted non-HDL-C, and the efficacy of triple combination therapies, including statins, ezetimibe, and fibrates, has yet to be determined. Methods: This is a multicenter, prospective, randomized, open-label, active-comparator controlled trial involving 3,958 eligible participants with T2D, cardiovascular risk factors, and elevated non-HDL-C (≥100 mg/dL). Participants, already on moderate-intensity statins, will be randomly assigned to either Ezefeno (ezetimibe/fenofibrate) addition or statin dose-escalation. The primary end point is the development of a composite of major adverse cardiovascular and diabetic microvascular events over 48 months. Conclusion This trial aims to assess whether combining statins, ezetimibe, and fenofibrate is as effective as, or possibly superior to, statin monotherapy intensification in lowering cardiovascular and microvascular disease risk for patients with T2D. This could propose a novel therapeutic approach for managing dyslipidemia in T2D.

Background: Current international guidelines recommend against deep sedation as it is associated with worse outcomes in the intensive care unit (ICU). However, in Korea the prevalence of deep sedation and its impact on patients in the ICU are not well known. Methods: From April 2020 to July 2021, a multicenter, prospective, longitudinal, noninterventional cohort study was performed in 20 Korean ICUs. Sedation depth extent was divided into light and deep using a mean Richmond Agitation–Sedation Scale value within the first 48 hours. Propensity score matching was used to balance covariables; the outcomes were compared between the two groups. Results: Overall, 631 patients (418 [66.2%] and 213 [33.8%] in the deep and light sedation groups, respectively) were included. Mortality rates were 14.1% and 8.4% in the deep and light sedation groups (P = 0.039), respectively. Kaplan-Meier estimates showed that time to extubation (P < 0.001), ICU length of stay (P = 0.005), and death P = 0.041) differed between the groups. After adjusting for confounders, early deep sedation was only associated with delayed time to extubation (hazard ratio [HR], 0.66; 95% confidence inter val [CI], 0.55– 0.80; P < 0.001). In the matched cohort, deep sedation remained significantly associated with delayed time to extubation (HR, 0.68; 95% 0.56–0.83; P < 0.001) but was not associated with ICU length of stay (HR, 0.94; 95% CI, 0.79–1.13; P = 0.500) and in-hospital mortality (HR, 1.19; 95% CI, 0.65–2.17; P = 0.582). Conclusion In many Korean ICUs, early deep sedation was highly prevalent in mechanically ventilated patients and was associated with delayed extubation, but not prolonged ICU stay or in-hospital death.

Purpose: Total hip arthroplasty (THA) using dual mobility components (DMC) is a reasonable surgical option for displaced femoral neck fractures in elderly patients, resulting in lower dislocation rates and improved stability. The purpose of this study was to investigate the clinical outcomes and risk factors responsible for mortality in elderly patients who were diagnosed with a displaced femoral neck fracture and had undergone DMC-THA. Materials and Methods: Out of 147 cases of THA from December 2018 to June 2020, a total of 79 cases were enrolled in this study, with the following characteristics: (1) Garden stage III or IV, (2) over 75 years of age, and (3) over 1 year of follow-up. All the patients received DMC-THA surgery using the anterolateral approach. Results: The mean follow-up period was 15.0±8.43 months and a total of one dislocation case was observed. The mortality rate was 17.7% (14/79), and it was especially higher in patients with a past medical history of malignancy (odds ratio [OR]=7.18, p=0.03) or a cognitive disorder such as dementia (OR=5.48, p=0.03). Preoperative low initial hemoglobin levels (OR=0.65, p=0.04) and low UCLA (Uni-versity of California at Los Angeles) score (OR=0.47, p=0.02) were also associated with mortality. Conclusion When considering THA as a treatment approach in elderly patients with a displaced femoral neck fracture, a high mortality rate is expected in patients with low preoperative hemoglobin levels or a history of malignancy or cognitive disorders. Hence, thorough monitoring and management should be undertaken before and after surgery.

Background: Serotonin syndrome is a life-threatening disease if not appropriately treated. This study aimed to investigate the prescription status of contraindicated drug combinations that cause serotonin syndrome and identify the related factors. Methods: A cross-sectional study was conducted using nationwide claims data. Adult patients taking serotonergic drugs with Parkinson’s disease or mental disorders were selected. Based on international medical databases (MDBs) and the Korean Drug Utilization Review (DUR), the status of prescribing contraindicated drug combinations that induce serotonin syndrome, the related factors, and the difference between international MDBs and the Korean DUR were analyzed. Results: Of the 49,773 study subjects, 163 (0.3%) were prescribed contraindicated serotonergic drug combinations based on international MDBs, and among them, only 105 (64.4%) were contraindicated by the Korean DUR. Positive influencing factors for prescribing contraindicated drug combinations include patient age between 65 and 74 and physician’s specialties (neurologists, and orthopedists). Negative influencing factors were physician’s specialty (internists) and medical institution (primary institutions). Conclusion Despite the implementation of DUR, 3 out of 1,000 study subjects received contraindicated drug combinations that caused serotonin syndrome. Hence, it is necessary to comply with the DUR and improve it in accordance with international MDBs.

Purpose: This study was performed to compare the clinical results and radiological follow-up differences between intertrochanteric fractures treated with the U-blade Gamma3 nail or the Zimmer natural nail (ZNN). Materials and Methods: The medical records of 129 cases diagnosed with an intertrochanteric frac-ture (90 cases of U-blade Gamma3 nail, 39 cases of ZNN) from July 2015 to December 2018 were reviewed. Patients were assigned to a U-blade Gamma3 nail (n=39) or a ZNN (n=39) group. To reduce selective bias, groups were subjected to Propensity score matching by age, body mass index, bone mineral density, and fracture type. Patients that met the following criteria were excluded; age <65 years, non-ambulatory, high energy or pathologic fracture, and a follow-up of <6 months. Operation times, estimated blood losses, preoperative and postoperative Koval grades, Harris hip score and radiological lag screw positions in the femoral head, reduction quality, cut-out, tip-apex distance (TAD), lag screw sliding distances, and times to union were compared. Results: Clinical results were similar in the two groups, but lag screw TAD was significantly greater in Ublade Gamma3 nail group (23.4 mm vs. 21.0 mm) (p=0.042). One case of cut-out occurred in the Ublade Gamma3 nail group, but no other nail-related postoperative complication was noted. Conclusion No significant difference was observed between the outcomes of U-blade Gamma3 nail or ZNN treatments of intertrochanteric fractures. We conclude that the U-blade confers no specific advan-tage.

Purpose: This study was performed to compare the clinical results and radiological follow-up differences between intertrochanteric fractures treated with the U-blade Gamma3 nail or the Zimmer natural nail (ZNN). Materials and Methods: The medical records of 129 cases diagnosed with an intertrochanteric frac-ture (90 cases of U-blade Gamma3 nail, 39 cases of ZNN) from July 2015 to December 2018 were reviewed. Patients were assigned to a U-blade Gamma3 nail (n=39) or a ZNN (n=39) group. To reduce selective bias, groups were subjected to Propensity score matching by age, body mass index, bone mineral density, and fracture type. Patients that met the following criteria were excluded; age <65 years, non-ambulatory, high energy or pathologic fracture, and a follow-up of <6 months. Operation times, estimated blood losses, preoperative and postoperative Koval grades, Harris hip score and radiological lag screw positions in the femoral head, reduction quality, cut-out, tip-apex distance (TAD), lag screw sliding distances, and times to union were compared. Results: Clinical results were similar in the two groups, but lag screw TAD was significantly greater in Ublade Gamma3 nail group (23.4 mm vs. 21.0 mm) (p=0.042). One case of cut-out occurred in the Ublade Gamma3 nail group, but no other nail-related postoperative complication was noted. Conclusion No significant difference was observed between the outcomes of U-blade Gamma3 nail or ZNN treatments of intertrochanteric fractures. We conclude that the U-blade confers no specific advan-tage.

Background/Aims: Needle knife fistulotomy (NKF) is a technique to facilitate pancreatic and biliary duct access during ERCP. The double-guidewire technique (DGT) is also used in cases of difficult cannulation, but it can increase the incidence of post-ERCP-pancreatitis (PEP). This study examined the success and complication rates of NKF after unsuccessful standard cannulation or DGT in patients with pancreaticobiliary disease. Methods: The data of 209 patients who received NKF as a rescue procedure between January 2009 and December 2016 were reviewed retrospectively. The cannulation success and complication rates were assessed. Results: The overall cannulation success rate was 90.4%. The success rates of patients who received NKF after standard cannulation or DGT were similar (82.6% [142/172] and 73.0% [27/37], respectively, p=0.179). Furthermore, there was no significant difference in the incidence of procedure-related adverse events between the two groups (10.5% [18/172] and 16.2% [6/37], respectively, p=0.391). Endoscopic retrograde pancreatic drainage (ERPD) insertion decreased the incidence of PEP (0% [0/16] in ERPD and 14.6% [19/130] in non-ERPD, p=0.132) among patients who received PD cannulation. Conclusions NKF is an effective and safe method that can be considered for rescue management after the initial failure of standard cannulation or DGT. NKF following standard cannulation can be preferred over NKF following DGT because of the higher success rate and the lower rate of pancreatitis, but the difference was not significant. PD stenting in patients at high risk of PEP can be considered to decrease pancreatitis.

PURPOSE: To compare outcomes (i.e., clinical and radiological findings, postoperative complication) in the fixation of intertrochanteric fractures with U-blade Gamma3 and Gamma3 nails. MATERIALS AND METHODS: A review of 162 patients (both male and female) treated for intertrochanteric fractures between December 2012 and December 2018 was conducted. All patients were older than 65 years of age and treated with U-blade Gamma3 (n=90) or Gamma3 (n=72) nails. Evaluations included: (i) screw-head position, (ii) fracture-reduction status, (iii) time to union, (iv) cases of cut-out, (v) tip-apex distance, and (vi) lag screw sliding distance. Differences in pre- and postoperative ambulatory ability was also investigated. RESULTS: There were no significant differences in baseline demographics between the two groups. While the lag-screw sliding distance was significantly shorter in U-blade Gamma3 nail group (4.7 mm vs. 3.6 mm; P=0.025), the mean time to union was similar between the groups (P=0.053). Three and six cases of cut-out were noted in the U-blade Gamma3 and Gamma3 nail groups, respectively (P=0.18), however no other postoperative complications were noted in either group. Lastly, there was no difference between the change from pre- to postoperative activity level between the groups (P=0.753). CONCLUSION Of all the clinical and radiological outcomes assessed, the only significant improvement between those treated with U-Blade Gamma and Gamma3 nails was a shorter lag-screw sliding distance. These findings should benefit clinicians when deciding between the use of U-Blade Gamma or Gamma3 nails.

Tryptamines are monoamine alkaloids with hallucinogenic properties and are widely abused worldwide. To hasten the regulations of novel substances and predict their abuse potential, we designed and synthesized four novel synthetic tryptamine analogs: Pyrrolidino tryptamine hydrochloride (PYT HCl), Piperidino tryptamine hydrochloride (PIT HCl), N,N-dibutyl tryptamine hydrochloride (DBT HCl), and 2-Methyl tryptamine hydrochloride (2-MT HCl). Then, we evaluated their rewarding and reinforcing effects using the conditioned place preference (CPP) and self-administration (SA) paradigms. We conducted an open field test (OFT) to deter-mine the effects of the novel compounds on locomotor activity. A head-twitch response (HTR) was also performed to characterize their hallucinogenic properties. Lastly, we examined the effects of the compounds on 5-HTR1a and 5-HTR2a in the prefrontal cortex using a quantitative real-time polymerase chain reaction (qRT-PCR) assay. None of the compounds induced CPP in mice or initiated SA in rats. PYT HCl and PIT HCl reduced the locomotor activity and elevated the 5-HTR1a mRNA levels in mice. Acute and repeated treatment with the novel tryptamines elicited HTR in mice. Furthermore, a drug challenge involving a 7-day abstinence from drug use produced higher HTR than acute and repeated treatments. Both the acute treatment and drug challenge increased the 5-HTR2a mRNA levels. Ketanserin blocked the induced HTR. Taken together, the findings suggest that PYT HCl, PIT HCl, DBT HCl, and 2-MT HCl produce hallucinogenic effects via 5-HTR2a stimulation, but may have low abuse potential.

PURPOSE: With the emergence of next-generation sequencing (NGS) technology, profiling a wide range of genomic alterations has become a possibility resulting in improved implementation of targeted cancer therapy. In Asian populations, the prevalence and spectrum of clinically actionable genetic alterations has not yet been determined because of a lack of studies examining high-throughput cancer genomic data. MATERIALS AND METHODS: To address this issue, 1,071 tumor samples were collected from five major cancer institutes in Korea and analyzed using targeted NGS at a centralized laboratory. Samples were either fresh frozen or formalin-fixed, paraffin embedded (FFPE) and the quality and yield of extracted genomic DNA was assessed. In order to estimate the effect of sample condition on the quality of sequencing results, tissue preparation method, specimen type (resected or biopsied) and tissue storage time were compared. RESULTS: We detected 7,360 non-synonymous point mutations, 1,164 small insertions and deletions, 3,173 copy number alterations, and 462 structural variants. Fifty-four percent of tumors had one or more clinically relevant genetic mutation. The distribution of actionable variants was variable among different genes. Fresh frozen tissues, surgically resected specimens, and recently obtained specimens generated superior sequencing results over FFPE tissues, biopsied specimens, and tissues with long storage duration. CONCLUSION: In order to overcome, challenges involved in bringing NGS testing into routine clinical use, a centralized laboratory model was designed that could improve the NGS workflows, provide appropriate turnaround times and control costs with goal of enabling precision medicine.
Academies and Institutes ; Asian Continental Ancestry Group ; DNA ; Humans ; Korea ; Methods ; Paraffin ; Point Mutation ; Precision Medicine ; Prevalence