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Objective: To investigate the real-world efficacy and toxicity of paclitaxel-cisplatin-bevacizumab and identify prognostic factors for paclitaxel-cisplatin-bevacizumab in platinum-naïve primary stage IVB cervical cancer. Materials and methods: We retrospectively reviewed patients with stage IVB cervical cancer who received paclitaxel-cisplatin-bevacizumab as first-line treatment between July 2015 and December 2021 at Asan Medical Center, Korea. Patient data including clinicopathologic characteristics, imaging, paclitaxel-cisplatin-bevacizumab administration, recurrence, and survival were collected. Results: Overall, 61 patients were included in this study. The median age of the patients was 56 (range, 28−79) years. Patients received a median of 9 (range, 2−30) cycles of paclitaxel-cisplatin-bevacizumab. The most common adverse event (all grades) during treatment was azotemia (80.3 %). Dose reduction and drug interruption were conducted in 41.0 % and 26.2 % of patients, respectively. The median progression-free survival (PFS) and the median overall survival (OS) were 11.8 (95 % confidence interval [CI], 9.3−14.2) and 24.3 (95 % CI, 16.9−31.7) months, respectively. Multivariate analysis indicated that cervical mass size reduction rate ≥40 % at the longest diameter was an independent prognostic factor for PFS (adjusted hazard ratio, 0.24; 95 % CI, 0.11−0.53; p

Diabetes is a chronic metabolic disorder characterized by elevated blood glucose levels, posing significant health risks such as cardiovascular disease, and nerve, kidney, and eye damage. Effective management of blood glucose is essential for individuals with diabetes to mitigate these risks. This study introduces the Glu-Ensemble, a deep learning framework designed for precise blood glucose forecasting in patients with type 2 diabetes. Unlike other predictive models, Glu-Ensemble addresses challenges related to small sample sizes, data quality issues, reliance on strict statistical assumptions, and the complexity of models. It enhances prediction accuracy and model generalizability by utilizing larger datasets and reduces bias inherent in many predictive models. The framework's unified approach, as opposed to patient-specific models, eliminates the need for initial calibration time, facilitating immediate blood glucose predictions for new patients. The obtained results indicate that Glu-Ensemble surpasses traditional methods in accuracy, as measured by root mean square error, mean absolute error, and error grid analysis. The Glu-Ensemble framework emerges as a promising tool for blood glucose level prediction in type 2 diabetes patients, warranting further investigation in clinical settings for its practical application.

Background: This study aimed to assess the feasibility and efficacy of neoadjuvant chemotherapy (NACT) in treating patients with high-grade neuroendocrine carcinoma of the uterine cervix (HGNEC). Methods: We performed a retrospective case-control study at Asan Medical Center, Seoul, Republic of Korea, from January 1993 to December 2017, involving 60 patients with surgically treated HGNEC. Thirteen patients (21.7%) received NACT before undergoing surgery. Regarding the comparison between the group that underwent NACT and the group that did not, we used a propensity score-matched analysis, matching 22 patients in the primary radical surgery group with 11 patients in the neoadjuvant chemotherapy followed by radical hysterectomy group. Results: In the entire cohort, primary open surgery was more common in the primary surgery group compared to the NACT group (p = 0.004). After propensity score matching (PSM), the median tumor size was 3.5 cm in the primary surgery group and 2.4 cm in the NACT group (p = 0.078). After matching, there was no significant difference in the recurrence rate between the two groups (63.6% in the primary surgery group vs. 63.6% in the neoadjuvant chemotherapy group, p = 0.782). After PSM, the primary surgery group exhibited a lower intraoperative transfusion rate (10%) than the NACT group (45.5%, p = 0.052). Conclusions: While NACT was feasible in patients with HGNEC, it did not significantly improve the survival rate over primary radical surgery.

Progressive familial intrahepatic cholestasis (PFIC) is an autosomal recessive inherited disease requiring liver transplantation (LT). Hepatocellular carcinoma (HCC) is very rare in infants. We present a case of living donor LT using a left lateral section graft performed in a 7-month-old female infant diagnosed with PFIC type II and HCC. No mutation on ABCB11 gene was identified. Because of progressive deterioration of liver function, living donor LT with her mother’s left lateral section graft was performed. Pretransplant serum alpha-fetoprotein (AFP) level was increased to 2,740 ng/mL, but HCC was not taken into account because of its rarity. The explant liver showed micronodular liver cirrhosis, multiple infantile hemangiomas and two HCCs of 0.7 cm and 0.3 cm in size. The patient recovered uneventfully from the LT operation. This patient has been regularly followed up with abdomen ultrasonography and AFP measurement every 6 months. The patient has been continually doing well for 8 years after the LT. In conclusion, LT is currently the only effective treatment for PFIC-associated end-stage liver diseases. HCC can develop at the cirrhotic liver of any cause, thus elevation of HCC tumor markers in pediatric patients is an important clue to perform further investigation before LT.

Background Dipeptidyl peptidase-4 (DPP-4) inhibitor has been reported to have kidney-protective benefits. To elucidate how antidiabetic agents prevent diabetic kidney disease progression, it is important to investigate their effect on the kidney environment in type 2 diabetes mellitus (DM) patients. Herein, we investigated the expression pattern of urinary exosome-derived microRNA (miRNA) in patients taking a combination of DPP-4 inhibitor and metformin (DPP-4 inhibitor group) and compared them with patients taking a combination of sulfonylurea and metformin (sulfonylurea group). Methods This was a prospective study involving 57 patients with type 2 DM (DPP-4 inhibitor group, n = 34; sulfonylurea group, n = 23) and healthy volunteers (n = 7). We measured urinary exosomal miRNA using the NanoString nCounter miRNA array (NanoString Technologies) across the three groups (n = 4 per each group) and validated findings using real-time polymerase chain reaction. Results Twenty-one differentially expressed candidate miRNAs were identified, and six (let-7c-5p, miR-23a-3p, miR-26a-3p, miR-30d, miR-205, and miR-200a) were selected for validation. Validation showed no significant difference in miRNA expression between the DPP-4 inhibitor and sulfonylurea groups. Only miR-23a-3p was significantly overexpressed in the diabetes group compared with the control group (DPP-4 inhibitor vs. control, p = 0.013; sulfonylurea vs. control, p = 0.007). This trend was consistent even after adjusting for age, sex, and body mass index. Conclusion There was no significant difference in urine exosome miRNA expression between diabetic participants taking DPP-4 inhibitor and those taking sulfonylurea. The miR-23a levels were higher in diabetic participants than in nondiabetic controls.

Congenital factor X (FX) deficiency is a rare autosomal-recessive disease that induces bleeding disorder. Herein, we present the 10-year posttransplant course of a pediatric patient who underwent liver transplantation (LT) with portal vein (PV) stenting for correction of severe congenital FX deficiency, with focus on long-term maintenance of coagulation function and patency of PV stenting. A 17-month-old infant with recurrent hemorrhagic episodes due to FX deficiency underwent split LT using a left lateral section graft. The graft-recipient weight ratio was 2.2%. The graft implantation procedures were performed by following the standard pediatric split LT procedure. Nevertheless, a wall stent was inserted due to PV anastomotic stenosis on posttransplant day 1. Graft function recovered slowly because of partial parenchyma infarct, and the patient was discharged at 46 days after LT operation. The FX activity started to increase soon after LT and gradually normalized; the coagulation profiles have been maintained well for the past 10 years. The patient has been doing well for the past 10 years after LT without any episodes of abnormal bleeding. Due to the risk of vascular complications owed to PV stenting, life-long follow-up is mandatory with special attention until attainment of complete physical growth to adolescent and adulthood.

Congenital absence of the portal vein (CAPV) is a rare venous malformation in which mesenteric venous blood drains directly into systemic circulation. Herein, we report a case of pediatric deceased donor liver transplantation (DDLT) for symptomatic CAPV with whole liver graft from a hepatitis B surface antigen (HBsAg)-positive donor. A 4-year-old boy suffered from CAPV and secondary portal hypertension. He was also diagnosed with DiGeorge syndrome and heart anomalies. After waiting for 4 months, a 5-year-old donor weighing 19 kg with positive HBsAg was allocated to this 4-year-old patient weighing 15 kg. Recipient operation was performed according to the standard procedures of pediatric DDLT. Portal vein reconstruction was performed using interposition of a vascular homograft conduit to the superior mesenteric vein-splenic vein confluence. The patient recovered uneventfully from DDLT. He has been administered with lamivudine to prevent hepatitis B virus infection. This patient has been doing well for 5 years after DDLT without growth retardation. In conclusion, CAPV patients can have various vascular anomalies, thus combined vascular anomalies should be thoroughly assessed before and during liver transplantation operation. The most effective reconstruction techniques should be used to achieve satisfactory results following liver transplantation.

Biliary atresia (BA)-polysplenia syndrome (PS) is diagnosed in a small proportion of BA patients. We present a case of split liver transplantation (LT) successfully performed in a pediatric recipient with BA-PS. The recipient was 29-month-old boy who underwent Kasai procedure. The coexisting malformations included agenesis of the inferior vena cava with azygos vein continuation, polysplenia, intestinal malrotation, truncated pancreas, and preduodenal portal vein and annular pancreas. With pediatric end-stage liver disease score of 33, the patient was allocated for split LT. Under this condition, the left lateral section graft was equivalent to a graft-recipient weight ratio of 2.6%. The recipient surgery was performed according to the standard procedures of pediatric LT. The graft hepatic vein was directly anastomosed with the suprahepatic confluence of the recipient hepatic veins. An external iliac vein homograft was interposed for portal vein reconstruction. Portal collateral veins were embolized intraoperatively to secure portal vein inflow. No surgical complications were developed. Currently, the patient has been doing well for 4 years after transplantation. Our pediatric patient with BA-PS had various anatomical malformations. Thorough preoperative and intraoperative assessment of these anomalies, adoption of customized reconstruction techniques of LT, and careful posttransplant monitoring are necessary for successful LT.

Background : We investigated the incidence and outcomes of pediatric deceased donor liver transplantation (DDLT) using whole liver grafts in a high-volume liver transplantation (LT) center. Methods : The study was a retrospective single-center analysis of whole LT in pediatric recipients. The study period was set as 20 years between January 2000 and December 2019. We defined pediatric recipients and donors to be aged ≤18 years. Results : During the study period, there were 98 cases of pediatric DDLT, and 34 patients (34.7%) received whole liver grafts. The age range of the deceased donors was 3 months to 56 years and that of pediatric recipients was 7 months to 17 years. Common primary diseases for LT were biliary atresia in 13, acute liver failure in four, Wilson disease in four, congenital portal vein agenesis in three, and genetic metabolic diseases in three. Pediatric-to-pediatric and adult-to-pediatric whole LTs were 22 (64.7%) and 12 (35.3%), respectively. A good correlation was noted between the donor and the recipient’s body weight, and the recipient’s body weight and allograft’s weight. Graft and overall patient survival rates were 91.2% and 91.2% at 1 year, 88.0% and 88.0% at 3 years, and 88.0% and 88.0% at 5 years, respectively. Conclusions: The results of this study revealed that Korean Network for Organ Sharing (KONOS) regulations with donor-recipient body weight matching exhibited good performance. Considering the reciprocal trades of liver organs among pediatric and adult donors and recipients, it is necessary to establish a policy for pediatric donor liver grafts to pediatric recipients on a priority basis.

We present a case of successful split liver transplantation (LT) using a hyperreduced left lateral segment (LLS) graft in a 106-day-old female infant patient weighing 4 kg. The patient was diagnosed with progressive familial intrahepatic cholestasis. Her general condition and liver function deteriorated progressively and she was finally allocated for a split LT under status 1. The deceased donor was a 20-year-old female weighing 63.7 kg. We performed in situ liver splitting and in situ size reduction sequentially. The weight of the hyperreduced LLS graft was 225 g, with a graft-recipient weight ratio of 5.5%. We performed recipient hepatectomy and graft implantation according to the standard procedures for pediatric living-donor LT. Since the graft was too large for primary abdomen closure, the abdominal wall was closed in three stages to make a prosthetic silo, temporary closure with a xenograft sheet, and final primary repair over 2 weeks. The patient has been doing well for more than 6 years after transplantation. In conclusion, split LT using a hyperreduced LLS graft can be a useful option for treating small infants. However, large-for-size graft-related problems, particularly in terms of graft thickness, still remain to be solved.

The tumor suppressor gene, p53, is inactivated in the human hepatocellular carcinoma cells line, Hep3B. Berberine has been reported to inhibit the proliferation of cancer cells. This study examined whether apoptosis was induced in berberine-treated Hep3B cells and observed the association between apoptosis and the expression of p53 and DNA methyltransferase (DNMT). The cell viability was measured using an MTT assay. Apoptosis of Hep3B was measured using annexin V flow cytometry. Berberine-treated cells were examined for their DNMT enzymatic activity, mRNA expression, and protein synthesis. The p53 levels were examined by Western blot analysis. The berberine treatment resulted in increased Hep3B cell death and apoptosis in a time- and dose-dependent manner. The DNMT3b activity, mRNA expression, and protein levels all decreased after the berberine treatment. In contrast, the p53 protein levels increased with a concomitant decrease in DNMT3b. No change in the expression of ERK was observed, but the P-ERK levels decreased in a dose dependent manner. These results indicate that a treatment of Hep3B cells with berberine can reduce the expression of DNMT3b, leading to an increase in the tumor suppressant gene p53 and an increase in cell apoptosis. This shows that berberine can effectively suppress the proliferation of liver cancer cells.

Forecasting blood glucose (BG) values for patients can help prevent hypoglycemia and hyperglycemia events in advance. To this end, this study proposes an intelligent ensemble deep learning system to predict BG values in 15, 30, and 60 min prediction horizons (PHs) based on historical BG values collected via continuous glucose monitoring devices as an endogenous factor and carbohydrate intake and insulin administration information (times) as exogenous factors. Although there are numerous deep learning algorithms available, this study applied five algorithms, namely, recurrent neural network (RNN), which is optimized for sequence data (e.g., time-series), and RNN-based algorithms (e.g., long short-term memory (LSTM), stacked LSTM, bidirectional LSTM, and gated recurrent unit). Then, a genetic algorithm (GA) was applied to the five prediction models to optimize their weights through ensemble techniques and to yield (output) the final predicted BG values. The performance of the proposed model was compared to that of the autoregressive integrated moving average (ARIMA) model as a baseline. The results show that the proposed model significantly outperforms the baseline in terms of the root mean square error (RMSE) and continuous glucose error grid analysis. For the valid 29 diabetic patients for the multivariate models, the RMSE was 11.08 (±3.19), 19.25 (±5.28), and 31.30 (±8.81) mg/DL for 15, 30, and 60 min PH, respectively. When the same data were applied to univariate models, the RMSE was 11.28 (±3.34), 19.99 (±5.59), and 33.13 (±9.27) mg/DL for 15, 30, and 60 min PH, respectively. Both the univariate and multivariate models showed a statistically significant difference compared with the baseline at a 5% statistical significance level. Instead of using a model with a single algorithm, applying a GA based on each output of a model with multiple algorithms was found to play a significant role in improving model performance.

Background Primary breast sarcoma (PBS) is rare, comprising approximately 1% of breast malignancies. Rhabdomyosarcoma (RMS) accounts for an extremely small proportion of PBSs, often leading to delayed histologic confirmation. Methods Upon reviewing Asan Medical Center’s pathology database between 2000 and 2018, 41 PBS cases were retrieved, including three cases of primary RMS of the breast. Their clinicopathological features were analyzed, and the literature related to PBS and primary RMS of the breast was reviewed. Results We identified three primary breast RMS cases from our institution database, comprising 7.3% of PBS: one case each of spindle cell/sclerosing RMS (ssRMS), alveolar RMS (aRMS), and embryonal RMS (eRMS). All cases involved adolescents or young adults (14, 16, and 25 years, respectively) who underwent mastectomy or radiotherapy and were confirmed using immunohistochemical testing for myogenin, desmin, and myogenic differentiation. The ssRMS patient experienced recurrence at the operation site 4 months post-surgery despite undergoing concurrent chemoradiotherapy. The aRMS patient had multiple metastases at diagnosis and showed FAX3-FOXO1 fusion transcripts; she died 22 months after the diagnosis. The eRMS patient had enlarged axillary lymph nodes; post-radiotherapy, the lesion recurred as multiple metastases to the bone and lung. She died 18 months post-diagnosis. Conclusions Our experience on RMS cases suggests that spindle cell or small round cell malignancy in breasts of young female should raise suspicion for the possibility of primary or secondary RMS. To our knowledge, this is the second report of primary breast ssRMS and it may help clinicians who encounter this rare disease in the future.

Abstract Background Palliative chemotherapy should be used with caution when attempting to alleviate symptoms in patients with end-stage cancer. However, palliative chemotherapy continues to be utilized in cancer patients during their last stages of life. In this study, we analyzed the pattern of chemotherapy administered during the last 6 months of life in patients with end-stage gynecologic cancer who were treated with active palliative chemotherapy for the past 10 years. Method We retrospectively analyzed the data for patients with gynecologic cancer who died after undergoing active palliative chemotherapy without receiving hospice management at Asan Medical Center from 2006 to 2015. Patients were divided into two groups: those who died between 2006 and 2010, and those who died between 2011 and 2015. Based on the electronic medical records, the demographic and baseline characteristics of the patients, hospital admission during the last 6 months, invasive procedures, palliative chemotherapy patterns, and the time of the last chemotherapy session were confirmed. Results A total of 193 patients with gynecologic cancer were eligible for this study. 92 patients died during 2006 to 2010, and 101 patients died during 2011 to 2015. The mean frequency of admission during the last 6 months was 5.12 for those who died in 2006–2010 and 6.06 for those who died during 2011–2015 (p = 0.003); similarly, the mean frequency of palliative chemotherapy during the last 6 months was 3.84 (2006–2010) vs. 4.93 times (2011–2015; p

Abstract Background Lymph node metastasis is a significant predictive factor for disease recurrence and survival in cervical cancer patients. Given the importance of lymph node metastasis, it is imperative that patients harboring metastasis are identified and can undergo appropriate treatment. Sentinel lymph node (SLN) mapping has drawn attention as a lymph node mapping technique. We evaluated the feasibility and efficacy of (SLN) mapping using indocyanine green (ICG) in cervical cancer. Methods We performed a single-center, retrospective study of 103 surgically treated cervical cancer patients who underwent SLN mapping. After using ICG to detect SLN during surgery, we removed the SLNs followed by laparoscopic or robotic-assisted radical surgery and bilateral pelvic lymphadenectomy. Results Stage IB1 was the most common (61.17%). At least one SLN was detected in all cases. Eighty-eight patients (85.44%) had bilateral pelvic SLNs. The mean number of SLN per patient was 2.34. The side-specific sensitivity was 71.43%, the specificity was 100%, the negative predictive value (NPV) was 93.98%, and the false negative rate (FNR) was 28.57%. In cases of tumors smaller than 2 cm with negative lymph node metastasis on imaging, the study revealed a side-specific sensitivity of 100%, a specificity of 100%, a NPV of 100%, and a FNR of 0%. Large tumor size (≥ 4 cm), a previous history of a loop electrosurgical excision procedure (LEEP), depth of invasion (≥ 50%), the microscopic parametrial (PM) invasion, and vaginal extension were significantly associated with the false-negative detection of SLN. Moreover, the microscopic PM invasion was the only risk factor of the false-negative detection of SLN in multivariate analysis. Conclusion SLN mapping with ICG in cervical cancer is feasible and has high detection rate. The sensitivity of 100% was high enough to perform SLN biopsy alone in an early stage in which the tumor is less than 2 cm, with no lymphadenopathy on image examination. However, for large or invasive tumors, we would have to be cautious about performing SLN biopsy alone. Trial registration Retrospectively registered 2017-0600.

Abstract Background We aimed to evaluate the efficacy and the safety of uterine preservation in patients with early-stage uterine adenosarcoma who want to preserve future fertility. Methods We performed a retrospective review of patients with stage I uterine adenosarcoma diagnosed and treated at a single institute from 1998 through 2014. Results Among the total of 31 patients, uterine preservation surgery was performed in 7 of the nulliparas. Of the 7 patients receiving uterine preservation surgery, 3 showed no evidence of disease (NED), 2 had persistent disease confined to the uterus, and 2 were alive with disease (AWD) after recurrence. One patient with an NED status had a vaginal delivery at term. In the uterine preservation group, 1 patient had sarcomatous overgrowth at the time of diagnosis and experienced disease recurrence. In the hysterectomy group, 3 of 24 patients had tumor recurrence. Of the five patients with tumor recurrence, four (80%) had sarcomatous overgrowth at diagnosis and it was significantly associated with recurrence by univariate analysis (OR 13.3, p = 0.027). Conclusions Uterine preservation represents a possible treatment option for young female patients who want to maintain fertility. However, a detailed explanation of the risk of recurrence is necessary, especially in patients with sarcomatous overgrowth, which seems to be associated with a higher risk of recurrence. Trial registration Retrospectively registered.

In this study, we propose a personalized glucose prediction model using deep learning for hospitalized patients who experience Type-2 diabetes. We aim for our model to assist the medical personnel who check the blood glucose and control the amount of insulin doses. Herein, we employed a deep learning algorithm, especially a recurrent neural network (RNN), that consists of a sequence processing layer and a classification layer for the glucose prediction. We tested a simple RNN, gated recurrent unit (GRU), and long-short term memory (LSTM) and varied the architectures to determine the one with the best performance. For that, we collected data for a week using a continuous glucose monitoring device. Type-2 inpatients are usually experiencing bad health conditions and have a high variability of glucose level. However, there are few studies on the Type-2 glucose prediction model while many studies performed on Type-1 glucose prediction. This work has a contribution in that the proposed model exhibits a comparative performance to previous works on Type-1 patients. For 20 in-hospital patients, we achieved an average root mean squared error (RMSE) of 21.5 and an Mean absolute percentage error (MAPE) of 11.1%. The GRU with a single RNN layer and two dense layers was found to be sufficient to predict the glucose level. Moreover, to build a personalized model, at most, 50% of data are required for training.

Objective: Malignant Brenner tumors (MBTs) of the ovary are very rare, and their definition, biology, and treatment modality have not been established. This study investigated the clinical characteristics of MBTs and the importance of chemotherapy for recurrent disease. Materials and methods: We conducted a retrospective analysis of 10 patients with MBT of the ovary treated at a single tertiary center from 1991 to 2013. Results: The median age was 55.5 years (range, 37–68 years). Nine of the 10 patients were symptomatic. The median size of the ovarian tumors was 10.5 cm (range, 2.5–25.0 cm). The cancer antigen-125 level was elevated in three patients. Six patients had a stage I tumor, one had a stage II tumor, two had a stage III tumor, and one had a stage IV tumor. Six patients received systemic adjuvant chemotherapy after surgery. The mean follow-up duration was 54.5 months (range, 8–173 months). Disease recurrence occurred in four of the 10 patients. The median time to recurrence was 11 months (range, 9–18 months). Two patients with locoregional recurrence showed favorable results after chemotherapy, regardless of the initial stage of the tumor. The patient with the stage IIIC tumor is alive at 13 months after recurrence on current chemotherapy. The patient with the stage IV tumor showed no evidence of the disease > 12 years after the last chemotherapy. Lastly, two patients with distant recurrence died after showing a long-term survival of 49 months and 88 months, respectively, after recurrence and intensive chemotherapy. Conclusion: Our results showed that systemic chemotherapy is beneficial in patients with recurrence of a primary MBT of the ovary, especially in the locoregional recurrence.

Objectives: Primary small cell carcinoma of the endometrium is a rare disease that can only be diagnosed at an advanced stage, and thus has a poor prognosis. In this study, the clinicopathologic characteristics of endometrial small cell carcinoma are described and the survival outcomes are discussed. Materials and methods: The data from six patients from a single medical institution who were diagnosed with endometrial small cell carcinoma in the past 20 years were retrospectively reviewed. Results: The median age of the six patients was 60 years. Vaginal bleeding was the most common symptom. All six patients underwent complete staging surgery, including hysterectomy, bilateral salpingoophorectomy, and systematic lymphadenectomy. Three of the patients were diagnosed with early stage disease, [International Federation of Gynecology and Obstetrics (FIGO) stage I or II], and the other three were in an advanced stage (FIGO stage III). Pathologically, deep myometrial invasion was observed in five (83.3%) of the patients, and lymphovascular invasion in six. As adjuvant therapy, four (66.7%) patients received platinum-based chemotherapy and one (16.7%) underwent concurrent chemoradiotherapy. During the median follow-up period of 16.2 months, recurrence developed in four patients (66.7%). There were disseminated recurrences on the peritoneum and lymph nodes in two cases, and distant metastasis to the brain in the other two cases. The median time to recurrence was 7.5 months (range, 315 months). One patient died of disease. Conclusion: Small cell carcinoma of the endometrium shows an aggressive clinical behavior, such as a disseminated disease and distant metastasis within a short time to recurrence. Initial active management with complete surgical resection and systemic chemotherapy might improve outcomes, although further large studies should be done to confirm this.

Renal failure caused by scrub typhus is known to be reversible. In most cases, renal function is almost fully restored after appropriate antibiotic treatment. A 71-year-old man was diagnosed with scrub typhus complicated by renal failure. A renal biopsy revealed histopathologic findings consistent with acute tubulointerstitial nephritis. Renal function did not improve 18 months after discharge and the patient required continuous hemodialysis. Although severe renal failure requiring dialysis is a rare complication of scrub typhus, we describe a case of scrub typhus requiring maintenance hemodialysis. To the best of our knowledge, this is the first such report.

Objective: To investigate the surgical and obstetric outcomes after adnexal surgery during pregnancy, focusing on the comparison between laparotomic and laparoscopic approaches. Materials and Methods: We retrospectively reviewed the medical charts for women who underwent surgery for adnexal mass or torsion during pregnancy between November 1991 and November 2011. Results: In a total of 152 women, the mean gestational age at surgery was 14.8 ± 4.1 weeks, and most operations were performed at second trimester (64.5%). Adnexal torsion was detected in 27 patients (17.8%), and malignant pathology was confirmed in four patients (2.6%). Among 111 patients who were followed up until delivery, postoperative adverse outcomes were observed in only two patients (1.8%) with miscarriage and 16 patients (14.4%) with preterm labor. Comparison between the laparotomy (118 patients, 77.6%) and laparoscopy (34 patients, 22.4%) groups showed that the latter had a shorter postoperative hospital stay and better surgical outcome than the former (5.9 ± 2.5 days vs. 2.4 ± 0.7 days, p

Background: Muscular strength is a powerful marker of current health status and robust predictor of age-related disease and disability. Handgrip strength (HGS) using isometric dynamometry is a convenient, feasible, and widely used method of assessing muscular strength among people of all ages. While adult HGS norms have been published for many countries, no study has yet synthesized available data to produce international norms. The objective of this study was to generate international sex- and age-specific norms for absolute and body size-normalized HGS across the adult lifespan. Methods: Systematic searches were conducted in 6 databases/web search engines (MEDLINE, SPORTDiscus, Embase, Web of Science, CINAHL, and Google Scholar) up to December 1, 2023. We included full-text peer-reviewed observational studies that reported normative HGS data for adults aged ≥20 years by sex and age. Pseudo data were generated using Monte Carlo simulation following harmonization for methodological variation. Population-weighted Generalized Additive Models for Location, Scale, and Shape were used to develop sex- and age-specific norms for absolute HGS (kg) and HGS normalized by height (Ht, m) squared (i.e., HGS/Ht2 in kg/m2). Norms were tabulated as percentile values (5th to 95th) and visualized as smoothed percentile curves. Results: We included data from 100 unique observational studies representing 2,405,863 adults (51.9% female) aged 20 to 100+ years from 69 countries and regions tested from the year 2000 onward. On average, absolute and normalized HGS values negligibly improved throughout early adulthood, peaked from age 30–39 years (at 49.7 kg (males) and 29.7 kg (females) for absolute HGS or 16.3 kg/m2 (males) and 11.3 kg/m2 (females) for HGS/Ht2), and declined afterwards. The age-related decline in HGS accelerated from middle to late adulthood and was slightly larger for males than for females during middle adulthood. Conclusion: This study provides the world's largest and most geographically comprehensive international norms for adult HGS by sex and age. These norms have utility for global peer-comparisons, health screening, and surveillance.

To evaluate the clinical role of adjuvant chemotherapy (AC) in FIGO stage IB-IIA cervical cancer patients.A cohort of 262 patients with cervical cancer who received radical hysterectomy (RH) and adjuvant therapy at Asan Medical Center between 1992 and 2012 was enrolled. In this cohort, 85 patients received adjuvant chemotherapy (AC), and 177 received adjuvant radiotherapy or concurrent chemoradiation therapy (AR). Oncologic outcomes and adverse events in both treatment arms were compared using weighted Cox proportional hazards regression models with inverse-probability-of-treatment weighting (IPTW) to reduce the impact of treatment selection bias and potential confounding factors.During a 46.8-month median follow-up duration, 39 patients (14.9%) had recurrences, and 18 patients (6.9%) died of disease. In multivariate analysis, the hazard ratio (HR) for recurrence and death was not significantly different in patients in either treatment arm (p=0.62 and 0.12, respectively). Also, after IPTW matching, the HR for recurrence did not significantly differ between the arms (HR 1.57, 95% CI 0.68-3.62, p=0.29). Similarly, disease-free survival and overall survival were not significantly different between the arms (p=0.47 and 0.13, respectively). In addition, patients with AC had a much lower prevalence of long-term complications (lymphedema: n=8 (9.4%) vs. 46 (26.0%), p=0.03; ureteral stricture: n=0 vs. 9 (6.2%), p=0.05).Patients with FIGO stage IB-IIA cervical cancer can benefit from AC after RH with fewer long-term complications and non-inferior therapeutic effect to AR. Chemotherapy may therefore be an alternative adjuvant treatment option for cervical cancer, particularly in younger patients.

The TP53 mutations have been proved to be predominated in ovarian cancer in a study from The Cancer Genome Atlas (TCGA). However, the molecular characteristics of recurrent ovarian cancers following initial treatment have been poorly estimated. This study was to investigate the pattern of somatic point mutations in matched paired samples of primary and recurrent epithelial ovarian cancers, using the OncoMap mutation detection protocol. We have adapted a high-throughput genotyping platform to determine the mutation status of a large panel of known cancer genes. OncoMap v.4.4 was used to evaluate genomic DNA isolated from a set of 92 formalin-fixed, paraffin-embedded (FFPE) tumors, consisting of matched paired samples of initially diagnosed and recurrent tumors from 46 epithelial ovarian cancer (EOC) patients. Mutations were observed in 33.7% of the samples, with 29.3% of these samples having a single mutation and the remaining 4.3% having two or more mutations. Among the 41 genes analyzed, 35 mutations were found in four genes, namely, CDKN2A (2.2%), KRAS (6.5%), MLH1 (8.2%) and TP53 (20.7%). TP53 was the most frequently mutated gene, but there was no correlation between the presence of mutation in any gene and clinical prognosis. Furthermore, somatic mutations did not differ between primary and recurrent ovarian carcinomas. Every mutation present in recurrent samples was detected in the corresponding primary sample. In conclusion, these OncoMap data of Korean EOC samples provide that somatic mutations were found in CDKN2A, KRAS, MLH1, and TP53. No differences in mutational status between primary and recurrent samples were detected. To understand the biology of tumor recurrence in epithelial ovarian cancer, more studies are necessary, including epigenetic modifications or additional mutations in other genes.

Hirschsprung disease (HSCR) is a congenital and heterogeneous disorder characterized by the absence of intramural nervous plexuses along variable lengths of the hindgut. Although RET is a well-established risk factor, a recent genome-wide association study (GWAS) of HSCR has identified NRG1 as an additional susceptibility locus. To discover additional risk loci, we performed a GWAS of 123 sporadic HSCR patients and 432 unaffected controls using a large-scale platform with coverage of over 1 million polymorphic markers. The result was that our study replicated the findings of RET-CSGALNACT2-RASGEF1A genomic region (rawP = 5.69×10(-19) before a Bonferroni correction; corrP = 4.31×10(-13) after a Bonferroni correction) and NRG1 as susceptibility loci. In addition, this study identified SLC6A20 (adjP = 2.71×10(-6)), RORA (adjP = 1.26×10(-5)), and ABCC9 (adjP = 1.86×10(-5)) as new potential susceptibility loci under adjusting the already known loci on the RET-CSGALNACT2-RASGEF1A and NRG1 regions, although none of the SNPs in these genes passed the Bonferroni correction. In further subgroup analysis, the RET-CSGALNACT2-RASGEF1A genomic region was observed to have different significance levels among subgroups: short-segment (S-HSCR, corrP = 1.71×10(-5)), long-segment (L-HSCR, corrP = 6.66×10(-4)), and total colonic aganglionosis (TCA, corrP>0.05). This differential pattern in the significance level suggests that other genomic loci or mechanisms may affect the length of aganglionosis in HSCR subgroups during enteric nervous system (ENS) development. Although functional evaluations are needed, our findings might facilitate improved understanding of the mechanisms of HSCR pathogenesis.

The Korean Society of Gynecologic Oncology has updated its clinical practice guidelines for endometrial cancer to incorporate advancements in recent high-quality randomized controlled trials. These guidelines address evolving treatment paradigms, and are tailored to the Korean medical context. Key updates include a strong recommendation for doxorubicin/trabectedin combination therapy in metastatic or recurrent unresectable leiomyosarcoma based on the significant survival benefits demonstrated in a randomized controlled trial. For advanced or recurrent endometrial cancer, immune checkpoint inhibitors combined with chemotherapy have received strong recommendations, owing to their proven efficacy and increased accessibility in Korea. Conditional recommendations were made for combination therapies involving durvalumab and olaparib, reflecting their potential benefits, but acknowledging regulatory and accessibility constraints. These guidelines aim to provide evidence-based, practical strategies to optimize care for patients with endometrial cancer while addressing unmet clinical needs and adapting global advancements to Korea's healthcare environment. [ABSTRACT FROM AUTHOR]

Background: Bulky or multiple lymph node (LN) metastases are associated with poor prognosis in cervical cancer, and the size or number of LN metastases is not yet reflected in the staging system and therapeutic strategy. Although the therapeutic effects of surgical resection of bulky LNs before standard treatment have been reported in several retrospective studies, well-planned randomized clinical studies are lacking. Therefore, the aim of the Korean Gynecologic Oncology Group (KGOG) 1047/DEBULK trial is to investigate whether the debulking surgery of bulky or multiple LNs prior to concurrent chemoradiation therapy (CCRT) improves the survival rate of patients with cervical cancer IIICr diagnosed by imaging tests. Methods: The KGOG 1047/DEBULK trial is a phase III, multicenter, randomized clinical trial involving patients with bulky or multiple LN metastases in cervical cancer IIICr. This study will include patients with a short-axis diameter of a pelvic or para-aortic LN ≥2 cm or ≥3 LNs with a short-axis diameter ≥1 cm and for whom CCRT is planned. The treatment arms will be randomly allocated in a 1:1 ratio to either receive CCRT (control arm) or undergo surgical debulking of bulky or multiple LNs before CCRT (experimental arm). CCRT consists of extended-field external beam radiotherapy/pelvic radiotherapy, brachytherapy and LN boost, and weekly chemotherapy with cisplatin (40 mg/m2), 4--6 times administered intravenously. The primary endpoint will be 3-year progression-free survival rate. The secondary endpoints will be 3-year overall survival rate, treatment-related complications, and accuracy of radiological diagnosis of bulky or multiple LNs. [ABSTRACT FROM AUTHOR]

The Korean Society of Gynecologic Oncology (KSGO) had been making an effort to standardize and enhance the quality of domestic uterine corpus cancer treatment by developing updated clinical practice guidelines in 2021. The KSGO revised the guidelines based on a literature search using 4 key elements: Population, Intervention, Comparison, and Outcome framework. These elements include the evaluation of the efficacy and safety of immune checkpoint inhibitor treatment in recurrent/advanced endometrial cancer patients who have failed platinum-based chemotherapy, as well as the effect of combined treatment with trastuzumab in patients with HER2/neu-positive endometrial cancer. Additionally, the guideline assessed the efficacy and safety of omitting lymph node dissection in low-risk endometrial cancer patients, investigated the effect of sentinel lymph node mapping in early-stage endometrial cancer surgery, addressed the outcome of chemoradiation therapy as a postoperative treatment in patients with advanced (stage III-IVA) endometrial cancer, and explored the impact of initial treatment with immune checkpoint inhibitors on survival in patients with advanced or recurrent endometrial cancer patients. [ABSTRACT FROM AUTHOR]

Background. Salinity is a major abiotic stress that prevents normal plant growth and development, ultimately reducing crop productivity. This study investigated the effects of salinity stress on two wheat lines: PL1 (wild type) and PL6 (mutant line generated through gamma irradiation of PL1). Results. The salinity treatment was carried out with a solution consisting of a total volume of 200 mL containing 150 mM NaCl. Salinity stress negatively impacted germination and plant growth in both lines, but PL6 exhibited higher tolerance. PL6 showed lower Na+ accumulation and higher K+ levels, indicating better ion homeostasis. Genome-wide transcriptomic analysis revealed distinct gene expression patterns between PL1 and PL6 under salt stress, resulting in notable phenotypic differences. Gene ontology analysis revealed positive correlations between salt stress and defense response, glutathione metabolism, peroxidase activity, and reactive oxygen species metabolic processes, highlighting the importance of antioxidant activities in salt tolerance. Additionally, hormone-related genes, transcription factors, and protein kinases showed differential expression, suggesting their roles in the differential salt stress response. Enrichment of pathways related to flavonoid biosynthesis and secondary metabolite biosynthesis in PL6 may contribute to its enhanced antioxidant activities. Furthermore, differentially expressed genes associated with the circadian clock system, cytoskeleton organization, and cell wall organization shed light on the plant's response to salt stress. Conclusions. Understanding these mechanisms is crucial for developing stress-tolerant crop varieties, improving agricultural practices, and breeding salt-resistant crops to enhance global food production and address food security challenges. [ABSTRACT FROM AUTHOR]