Photodynamic therapy (PDT) is a promising therapeutic modality that involves the administration of a photosensitizer followed by local illumination with a specific wavelength of light in the presence of oxygen. PDT is minimally invasive, has high selectivity for cancer, and has good patient compliance due to the simplicity of the procedure; therefore, PDT is widely used as a palliative and salvage treatment in patients with various gastrointestinal malignancies. When used as a salvage treatment for locoregional failures after definitive chemoradiotherapy for esophageal cancer, favorable results have been reported. PDT in conjunction with biliary stenting is a promising palliative treatment for unresectable cholangiocarcinoma, and can be used as an advanced diagnostic and therapeutic strategy in peritoneal dissemination of gastric cancer. Recent clinical reports of PDT for treating non-resectable pancreatic cancer also show promising results. To widen the application of PDT, the integration of PDT with molecular imaging and nanotechnology is being extensively studied. Based on these new developments, PDT is likely to re-emerge as a valuable technique in the treatment of diverse gastrointestinal diseases.

Studies investigating diabetic nephropathy (DN) have mostly focused on interpreting the pathologic molecular mechanisms of DN, which may provide valuable tools for early diagnosis and prevention of disease onset and progression. Currently, there are few therapeutic drugs for DN, which mainly consist of antihypertensive and antiproteinuric measures that arise from strict renin-angiotensin-aldosterone system inactivation. However, these traditional therapies are suboptimal and there is a clear, unmet need for treatments that offer effective schemes beyond glucose control. The complexity and heterogeneity of the DN entity, along with ambiguous renal endpoints that may deter accurate appraisal of new drug potency, contribute to a worsening of the situation. To address these issues, current research into original therapies to treat DN is focusing on the intrinsic renal pathways that intervene with intracellular signaling of anti-inflammatory, antifibrotic, and metabolic pathways. Mounting evidence in support of the favorable metabolic effects of these novel agents with respect to the renal aspects of DN supports the likelihood of systemic beneficial effects as well. Thus, when translated into clinical use, these novel agents would also address the co-morbid factors associated with diabetes, such as obesity and risk of cardiovascular disease. This review will provide a discussion of the promising and effective therapeutic agents for the management of DN.

Gestational diabetes mellitus (GDM), defined as any degree of glucose intolerance with onset or first recognition during pregnancy, is characterized by underlying maternal defects in the ${\beta}$-cell response to insulin during pregnancy. Women with a previous history of GDM have a greater than 7-fold higher risk of developing postpartum diabetes compared with women without GDM. Various risk factors for postpartum diabetes have been identified, including maternal age, glucose levels in pregnancy, family history of diabetes, pre-pregnancy and postpartum body mass index, dietary patterns, physical activity, and breastfeeding. Genetic studies revealed that GDM shares common genetic variants with type 2 diabetes. A number of lifestyle interventional trials that aimed to ameliorate modifiable risk factors, including diet, exercise, and breastfeeding, succeeded in reducing the incidence of postpartum diabetes, weight retention, and other obesity-related morbidities. The present review summarizes the findings of previous studies on the incidence and risk factors of postpartum diabetes and discusses recent lifestyle interventional trials that attempted to prevent postpartum diabetes.

Recent advances in genome editing with programmable nucleases have opened up new avenues for multiple applications, from basic research to clinical therapy. The ease of use of the technology-and particularly clustered regularly interspaced short palindromic repeats (CRISPR)-will allow us to improve our understanding of genomic variation in disease processes via cellular and animal models. Here, we highlight the progress made in correcting gene mutations in monogenic hereditary disorders and discuss various CRISPR-associated applications, such as cancer research, synthetic biology, and gene therapy using induced pluripotent stem cells. The challenges, ethical issues, and future prospects of CRISPR-based systems for human research are also discussed.

Since the report of type 1 diabetes reversal in seven consecutive patients by the Edmonton protocol in 2000, pancreatic islet transplantation has been reappraised based on accumulated clinical evidence. Although initially expected to therapeutically target long-term insulin independence, islet transplantation is now indicated for more specific clinical benefits. With the long-awaited report of the first phase 3 clinical trial in 2016, allogeneic islet transplantation is now transitioning from an experimental to a proven therapy for type 1 diabetes with problematic hypoglycemia. Islet autotransplantation has already been therapeutically proven in chronic pancreatitis with severe abdominal pain refractory to conventional treatments, and it holds promise for preventing diabetes after partial pancreatectomy due to benign pancreatic tumors. Based on current evidence, this review focuses on islet transplantation as a realistic approach to treating diabetes.

Background/Aims: The aim of this study was to compare the clinical features and outcomes of ulcerative colitis (UC) according to the age of onset in Korea. Methods: A total of 1,141 patients who were diagnosed with UC between July 1987 and November 2013 at 11 tertiary hospitals were enrolled. The baseline disease characteristic and disease state at onset, treatment during the disease course were retrospectively reviewed among patients with young-onset (YO, < 20 years) and adult-onset (AO, ${\geq}20years$). Severe outcome was defined as use of intravenous (IV) steroids, infliximab, immunosuppressant, or UC-related operation. Results: There were 55 YO patients (mean age, $17.8{\pm}2.4$) and 1,086 AO patients (mean age, $43.0{\pm}13.6$). High Mayo scores ($7.7{\pm}3.0$ vs. $5.6{\pm}2.7$, p = 0.000), extensive UC (52.7% vs. 25.8%, p = 0.000) and IV steroid (41.8% vs. 18.0%, p = 0.000), immunosuppressant (47.3% vs. 26.9%, p = 0.002), and infliximab (20.0% vs. 7.2%, p = 0.001) use were more frequent in the YO than in the AO group. According to multivariate analysis, severe outcomes were related to YO disease (hazard ratio [HR], 2.18; 95% confidence interval [CI], 1.27 to 3.71), body mass index < $23kg/m^2$ (HR, 1.46; 95% CI, 1.07 to 2.00), severe (HR, 2.29; 95% CI, 1.36 to 3.38), and moderate (HR, 2.48; 95% CI, 1.67 to 3.67) disease, extensive UC (HR, 2.90; 95% CI, 1.79 to 4.69), UC-related admission (HR, 63.89; 95% CI, 20.41 to 200.02), and oral steroid use (HR, 0.51; 95% CI, 0.39 to 0.67). Conclusions: UC with YO presented with more advanced clinical features at onset and more severe outcomes than the AO. YO cases require careful management and intense treatment strategies.

Background/Aims: Despite improvements in surgical techniques and postoperative patient care, bile leakage can occur after hepatobiliary surgery and may lead to serious complications. The aim of this retrospective study was to evaluate the efficacy of endoscopic treatment of bile leakage after hepatobiliary surgery. Methods: The medical records of 20 patients who underwent endoscopic retrograde cholangiopancreatography because of bile leakage after hepatobiliary surgery from August 2009 to September 2014 were reviewed retrospectively. Endoscopic treatment included insertion of an endoscopic retrograde biliary drainage stent after endoscopic sphincterotomy. Results: Most cases of bile leakage presented as percutaneous bile drainage through a Jackson-Pratt bag (75%), followed by abdominal pain (20%). The sites of bile leaks were the cystic duct stump in 10 patients, intrahepatic ducts in five, liver beds in three, common hepatic duct in one, and common bile duct in one. Of the three cases of bile leakage combined with bile duct stricture, one patient had severe bile duct obstruction, and the others had mild strictures. Five cases of bile leakage also exhibited common bile duct stones. Concerning endoscopic modalities, endoscopic therapy for bile leakage was successful in 19 patients (95%). One patient experienced endoscopic failure because of an operation-induced bile duct deformity. One patient developed guidewire-induced microperforation during cannulation, which recovered with conservative treatment. One patient developed recurrent bile leakage, which required additional biliary stenting with sphincterotomy. Conclusions: The endoscopic approach should be considered a first-line modality for the diagnosis and treatment of bile leakage after hepatobiliary surgery.

Background/Aims: Chronic thromboembolic pulmonary hypertension (CTEPH) is a life-threatening complication after acute pulmonary embolism (APE) and is associated with substantial morbidity and mortality. This study aimed to investigate the incidence of CTEPH after APE in Korea and to determine echocardiographic predictors of CTEPH. Methods: Among 381 patients with APE confirmed by chest computed tomography (CT) between January 2007 and July 2013, 246 consecutive patients with available echocardiographic data were enrolled in this study. CTEPH was defined as a persistent right ventricular systolic pressure (RVSP) greater than 35 mmHg on echocardiography during follow-up and persistent pulmonary embolism on the follow-up CT. Results: Fifteen patients (6.1%) had CTEPH. The rate of right ventricular (RV) dilatation (66.7% vs. 28.1%, p = 0.002) and the RVSP (75.5 mmHg vs. 39.0 mmHg, p < 0.001) were significantly higher in the CTEPH group. D-dimers, RV dilatation, RV hypertrophy, RVSP, and intermediate-risk APE were associated with the risk of CTEPH after APE (odds ratio [OR] 0.59, 5.11, 7.82, 1.06, and 4.86, respectively) on univariate analysis. RVSP remained as a significant predictor of CTEPH on multivariate analysis (OR, 1.056; 95% confidence interval, 1.006 to 1.109; p = 0.029). Conclusions: This study showed that the incidence of CTEPH after APE in Korea was 6.1% and that initial RVSP by echocardiography was a strong prognostic factor for CTEPH.

Background/Aims: This study aimed to investigate the risk factors associated with provoked pulmonary embolism (PE). Methods: This retrospective cohort study included 237 patients with PE. Patients that had transient risk factors at diagnosis were classified as having provoked PE, with the remaining patients being classified as having unprovoked PE. The baseline clinical characteristics and factors associated with coagulation were compared. We evaluated the risk factors associated with provoked PE. Results: Of the 237 PE patients, 73 (30.8%) had provoked PE. The rate of respiratory failure and infection, as well as the disseminated intravascular coagulation score and ratio of right ventricular diameter to left ventricular diameter were significantly higher in patients with provoked PE than in those with unprovoked PE. The protein and activity levels associated with coagulation, including protein C antigen, protein S antigen, protein S activity, anti-thrombin III antigen, and factor VIII, were significantly lower in patients with provoked PE than in those with unprovoked PE. Multivariate analysis showed that infection (odds ratio [OR], 3.2; 95% confidence interval [CI], 1.4 to 7.4) and protein S activity (OR, 0.97; 95% CI, 0.95 to 0.99) were significantly associated with provoked PE. Conclusions: Protein S activity and presence of infection were important factors associated with provoked PE. We should pay attention to the presence of infection in patients with provoked PE.

Background/Aims: Previous studies have suggested that elevated serum vitamin D levels might protect against thyroid cancer. Elevated serum thyroid stimulating hormone levels and autoimmune thyroid disease (AITD) are suggested to be thyroid cancer promoting factors but have not been well controlled in previous studies. We designed the present study to evaluate whether serum vitamin D levels are associated with thyroid cancer in euthyroid patients with no clinical evidence of AITD. Methods: This cross-sectional study included subjects who underwent routine health check-ups, including serum 25-hydroxy vitamin D3 (25(OH)D3) levels, anti-thyroid peroxidase antibody (TPO-Ab), and thyroid ultrasonography (US). Inclusion criteria were euthyroid, negative TPO-Ab, and no evidence of AITD by US findings. Thyroid cancer diagnoses were based on fine needle aspiration cytology and/or postsurgical histopathological findings. Results: We enrolled 5,186 subjects (64% male, 37% female) in this study, including 53 patients (1%) with a diagnosis of thyroid cancer (33 males, 20 females). Mean 25(OH)D3 levels were similar between the thyroid cancer and control groups (p = 0.20). Subgroup analysis according to sex or seasonal variation also revealed no differences in 25(OH)D3 levels between the two groups. Based on the levels of 25(OH)D3, there was no significant difference in the prevalence of thyroid cancer; the prevalence was 0.71%, 0.94%, 1.40%, and 0.82% in the deficient, insufficient, sufficient, and excess groups, respectively (p = 0.64). Conclusions: The levels of serum 25(OH)D3 are not associated with thyroid cancer prevalence in euthyroid subjects with no clinical evidence of AITD.

Background/Aims: The optimal serum bicarbonate level is controversial for patients who are undergoing hemodialysis (HD). In this study, we analyzed the impact of serum bicarbonate levels on mortality among HD patients. Methods: Prevalent HD patients were selected from the Clinical Research Center registry for End Stage Renal Disease cohort in Korea. Patients were categorized into quartiles according to their total carbon dioxide ($tCO_2$) levels: quartile 1, a $tCO_2$ of < 19.4 mEq/L; quartile 2, a $tCO_2$ of 19.4 to 21.5 mEq/L; quartile 3, a $tCO_2$ of 21.6 to 23.9 mEq/L; and quartile 4, a $tCO_2$ of ${\geq}24mEq/L$. Cox regression analysis was used to calculate the adjusted hazard ratio (HR) and confidence interval (CI) for mortality. Results: We included 1,159 prevalent HD patients, with a median follow-up period of 37 months. Kaplan-Meier analysis revealed that the all-cause mortality was significantly higher in patients from quartile 4, compared to those from the other quartiles (p = 0.009, log-rank test). The multivariate Cox proportional hazard model revealed that patients from quartile 4 had significantly higher risk of mortality than those from quartile 1, 2 and 3, after adjusting for the clinical variables in model 1 (HR, 1.99; 95% CI, 1.15 to 3.45; p = 0.01) and model 2 (HR, 1.82; 95% CI, 1.03 to 3.22; p = 0.04). Conclusions: Our data indicate that high serum bicarbonate levels (a $tCO_2$ of ${\geq}24mEq/L$) were associated with increased mortality among prevalent HD patients. Further effort might be necessary in finding the cause and correcting metabolic alkalosis in the chronic HD patients with high serum bicarbonate levels.

Background/Aims: We investigated which dialysis unit blood pressure (BP) is the most useful for predicting home BP in patients undergoing hemodialysis (HD). Methods: Patients undergoing HD who had been treated > 3 months were included in this study. Exclusion criteria were hospitalized patients with acute illness and changes in dry weight and anti-hypertensive drugs 2 weeks before the study. We used the dialysis unit BP recording data, such as pre-HD, intra-HD, post-HD, mean pre-HD, and post-HD (pre-post-HD), mean pre-HD, intra-HD, and post-HD (pre-intra-post-HD) BP. Home BP (the same period of dialysis unit BP) was monitored as a reference method during 2 weeks using the same automatic oscillometric device. Patients were asked to record their BP three times daily (wake up, between noon and 6:00 PM, and at bedtime). Results: Significant differences were detected between home systolic blood pressure (SBP) and pre-HD, post-HD, and intra-HD SBP (p = 0.003, p = 0.001, p = 0.016, respectively). In contrast, no differences were observed between home SBP and pre-intra-post-HD and pre-post-HD SBP (p = 0.235, p = 0.307, respectively). Areas under the receiver operating characteristic curve for pre-intra-post-HD and pre-post-HD SBP with 2-week home BP as the reference standard were 0.812 and 0.801, respectively. Conclusions: These results suggest that pre-intra-post-HD and pre-post-HD SBP had similar accuracy for predicting mean 2-week home SBP in HD patients. Therefore, pre-intra-post-HD and pre-post-HD SBP should be useful for predicting home SBP in HD patients if ambulatory or home BP measurements are unavailable.

Background/Aims: The aim of this study was to identify the role of BCR-ABL1 transcript level as a predictor for post-transplant relapse and outcome in patients who underwent allogeneic stem cell transplantation (SCT) for chronic phase (CP) chronic myeloid leukemia (CML). Methods: Of 101 patients receiving allograft in CML CP, 85 had available quantitative reverse transcriptase polymerase chain reaction data at post-transplant 3 months. These patients were divided into two groups according to molecular response ($MR^{4{\cdot}5}$), defined as a BCR-ABL1 transcript level ${\leq}0.0032%$ on the international scale, at 3 months based on receiver operating characteristic curve analysis of relapse. Results: The 4-year overall survival and event-free survival (EFS) were 80.6% and 57.3%, respectively, and the cumulative incidence of relapse at 4 years was 29.6% after a median follow-up of 126.4 months. We performed multivariate analyses including potential variables to evaluate the early predictive role of $MR^{4{\cdot}5}$ at 3 months and found that $MR^{4{\cdot}5}$ at 3 months was associated with a higher EFS (p = 0.028) and showed a trend for a lower relapse rate (p = 0.089). Conclusions: our results imply that frequent molecular monitoring and immune suppressive therapy modulation are required for patients without reduction of BCR-ABL1 transcripts to this level after SCT.

Background/Aims: Mucosal immunoglobulin A (IgA) may prevent the entrance of allergens. This study examined the relationship between serum IgA levels (within the normal range) and sensitization to house dust mites (HDM) or airway hyper-responsiveness (AHR). Methods: The clinical records of 1,136 adult patients with suspected asthma, for whom test data for serum IgA level and methacholine-AHR were available, were reviewed retrospectively. The AHR/allergy indices were compared among patient groups with low (<140 mg/dL, group I), intermediate (140 to 280 mg/dL, group II), or high (${\geq}280mg/dL$, group III) IgA levels in serum. Results: The HDM skin sensitization rate progressively decreased from 30.0% in group I (n = 139) to 26.8% and 18.5% in groups II (n = 684) and III (n = 313), respectively (p = 0.003). Although both the HDM sensitization degree and the IgA level were significantly related to age, the adjusted odds ratio (OR) of association of a high IgA level (${\geq}280mg/dL$) with HDM sensitization was significant (0.617; 95% confidence interval [CI], 0.415 to 0.916; p = 0.017). Among younger subjects (${\leq}45$ years of age) with AHR, the prevalence of moderate/severe AHR progressively decreased (70.6%, 52.3%, and 47.1% in groups I, II, and III [n = 34, 149, and 51]), respectively (p = 0.045). The IgA < 140 mg/dL was a significant risk factor for moderate/severe AHR (OR, 2.306; 95% CI, 1.049 to 5.071; p = 0.038). Conclusions: Sensitization to HDM and methacholine-AHR were significantly associated with serum IgA levels in suspected asthmatics, even when those levels were normal.

Background/Aims: Although multidrug resistance (MDR) among extended-spectrum ${\beta}$-lactamase-producing Escherichia coli (ESBL-EC) poses significant therapeutic challenges, little is known regarding the risk factors and epidemiology of community-onset MDR-ESBL-EC infections. We performed this study to investigate risk factors and the molecular epidemiology of community-onset MDR-ESBL-EC infections. Methods: We conducted a case-control-control study of community-onset infections. MDR-ESBL-EC was defined as ESBL-EC that demonstrated in vitro resistance to trimethoprim-sulfamethoxazole, fluoroquinolones (FQs), and gentamicin. Patients with MDR-ESBL-EC infections were designated as case patients. A control group I (CG I) patient was defined as a person whose clinical sample yielded ESBL-EC that did not meet the criteria for MDR. A control group II (CG II) patient was defined as a patient with a non-ESBL-EC infection. Results: Of 108 patients with ESBL-EC infections, 30 cases (27.8%) were due to MDR-ESBL-EC. Compared with CG I, prior use of FQs (odds ratio [OR], 3.16; 95% confidence interval [CI], 1.11 to 8.98) and immunosuppressant use (OR, 10.47; 95% CI, 1.07 to 102.57) were significantly associated with MDR-ESBL-EC. Compared with CG II, prior use of FQs (OR, 15.53; 95% CI, 2.86 to 84.27) and healthcare-associated infection (OR, 5.98; 95% CI, 2.26 to 15.86) were significantly associated with MDR-ESBL-EC. CTX-M-15 was the most common in MDR-ESBL-EC infections (59.1% [13/22]), while CTX-M-14 was the most common in non-MDR-ESBL-EC infections (41.6% [32/77]). CTX-M-15 was significantly associated with MDR-ESBL-EC (59.1% vs. 32.5%, p = 0.028). Pulsed-field gel electrophoresis showed clonal diversity of MDR-ESBL-EC isolates. Conclusions: The emergence of strains of MDR-ESBL-EC in the community poses an important new public health threat. More information on the emergence and transmission of these strains will be necessary in order to prevent their spread.

Background/Aims: To evaluate the clinical course of hip arthritis and the risk factors for hip joint replacement in patients with ankylosing spondylitis (AS). Methods: In this retrospective analysis, we evaluated 488 AS patients at a single tertiary hospital. At baseline and the most recent visit to the outpatient clinic from the patients with hip arthritis in AS, radiographic hip arthritis was evaluated using the Bath Ankylosing Spondylitis Radiology Hip Index (BASRI-h). Also the average of the hip joint space width (interbone distance) at three distinct sites between the acetabulum and femoral head was recorded. Results: Among 488 patients with AS, 60 patients (12.3%) had hip arthritis. Erythrocyte sedimentation rate were associated with hip involvement (odds ratio, 1.01; 95% confidence interval [CI], 1.00 to 1.02; p = 0.004). Long disease duration and advanced axial disease were associated with severe hip arthritis ($3{\geq}BASRI-h$) at baseline. BASRI-h and interbone distance did not significantly change in patients with hip involvement during the follow-up period of $81.4{\pm}35.7$ months. Five patients had hip joint replacement surgery during follow-up period. The body mass index (BMI) and BASRI-h at baseline were associated with joint replacement surgery (hazard ratio [HR], 1.30; 95% CI, 1.00 to 1.67; p = 0.049 and HR, 20.64; 95% CI, 2.39 to 178.11; p = 0.006, respectively). Conclusions: Most of the patients with hip arthritis in AS showed no significant radiographic progression during the follow-up period. High BMI and advanced hip arthritis at baseline were associated with hip joint replacement surgery in patients with AS.

Background/Aims: To determine the prevalence of autonomic dysfunction among Korean patients with primary Sjogren's syndrome (pSS) and its associations with the clinical features of pSS. Methods: We analyzed 154 participants from the Korean Initiative of primary Sjogren's Syndrome (KISS) as a prospective pSS cohort and 154 age- and sex-matched healthy controls. A standardized 5-minute, supine, resting heart rate variability (HRV) test was performed, and autonomic dysfunction was defined as standard deviation of normal-to-normal RR intervals (SDNN) < 30 ms in patients < 50 years old and SDNN < 20 ms in patients ${\geq}50$ years old. The associations between autonomic dysfunction and various clinical features of pSS were analyzed. Results: The overall autonomic activity in patients with pSS was significantly lower than that in controls. Autonomic dysfunction with the HRV test was observed in 35.7% of the KISS participants and was associated with a higher European League Against Rheumatism Sjogren's Syndrome Patient Reported Index fatigue score (p = 0.024). Raynaud's phenomenon was a more frequent clinical presentation in pSS patients with autonomic dysfunction than in those without autonomic dysfunction (29.4% and 14.4%, respectively; p = 0.048). Decreased parasympathetic activity was observed in 41.6% of pSS patients. No differences were found in the oral and ocular signs of pSS according to the decreased parasympathetic activity. Conclusions: In Korean patients with pSS, decreased and imbalanced autonomic activity is prevalent and is associated with fatigue. However, an association between autonomic dysfunction and glandular manifestations was not detected.

Falls and fall-related injuries are common in older populations and have negative effects on quality of life and independence. Falling is also associated with increased morbidity, mortality, nursing home admission, and medical costs. Korea has experienced an extreme demographic shift with its population aging at the fastest pace among developed countries, so it is important to assess fall risks and develop interventions for high-risk populations. Guidelines for the prevention of falls were first developed by the Korean Association of Internal Medicine and the Korean Geriatrics Society. These guidelines were developed through an adaptation process as an evidence-based method; four guidelines were retrieved via systematic review and the Appraisal of Guidelines for Research and Evaluation II process, and seven recommendations were developed based on the Grades of Recommendation, Assessment, Development, and Evaluation framework. Because falls are the result of various factors, the guidelines include a multidimensional assessment and multimodal strategy. The guidelines were developed for primary physicians as well as patients and the general population. They provide detailed recommendations and concrete measures to assess risk and prevent falls among older people.