A novel variant of PHEX in a Korean family with X-linked hypophosphatemic rickets

X-linked dominant hypophosphatemic rickets are the most common form of familial hypophosphatemic rickets resulting from hypophosphatemia caused by renal phosphate wasting, which in turn is a result of loss-of-function mutations in PHEX.Herein, we report a 39-year-old female with short stature and skeletal deformities and 12-month-old asymptomatic daughter.The female has a history of multiple surgical treatments because of lower limb deformities. Her biochemical findings revealed low serum phosphorus levels with elevated serum alkaline phosphatase activity and normal serum calcium levels, suggesting presence of hypophosphatemic rickets. To identify the molecular causes, we used a multigene testing panel and found a mutation, c.667dup (p.Asp223GlyfsTer15), in PHEX gene. To the best of our knowledge, this is a novel mutation. A heterozygous form of the same variant was detected in daughter, who showed no typical symptoms such as bow legs, frontal bossing, or waddling gate, but presented early signs of impaired mineralization in both X-ray and biochemical findings. The daughter was initiated onto early medical treatment with oral phosphate supplementation and an active vitamin D analog. Because the daughter was genetically diagnosed based on a family history before the onset of symptoms, appropriate medical management was possible from early infancy.

Machine learning based potentiating impacts of 12‑lead ECG for classifying paroxysmal versus non‑paroxysmal atrial fibrillation

Background@#Conventional modality requires several days observation by Holter monitor to differentiate atrial fibril‑ lation (AF) between Paroxysmal atrial fibrillation (PAF) and Non-paroxysmal atrial fibrillation (Non-PAF). Rapid and practical differentiating approach is needed. @*Objective@#To develop a machine learning model that observes 10-s of standard 12-lead electrocardiograph (ECG) for real-time classification of AF between PAF versus Non-PAF. @*Methods@#In this multicenter, retrospective cohort study, the model training and cross-validation was performed on a dataset consisting of 741 patients enrolled from Severance Hospital, South Korea. For cross-institutional validation, the trained model was applied to an independent data set of 600 patients enrolled from Ewha University Hospital, South Korea. Lasso regression was applied to develop the model. @*Results@#In the primary analysis, the Area Under the Receiver Operating Characteristic Curve (AUC) on the test set for the model that predicted AF subtype only using ECG was 0.72 (95% CI 0.65–0.80). In the secondary analysis, AUC only using baseline characteristics was 0.53 (95% CI 0.45–0.61), while the model that employed both baseline characteris‑ tics and ECG parameters was 0.72 (95% CI 0.65–0.80). Moreover, the model that incorporated baseline characteristics, ECG, and Echocardiographic parameters achieved an AUC of 0.76 (95% CI 0.678–0.855) on the test set. @*Conclusions@#Our machine learning model using ECG has potential for automatic differentiation of AF between PAF versus Non-PAF achieving high accuracy. The inclusion of  Echocardiographic parameters further increases model per‑ formance. Further studies are needed to clarify the next steps towards clinical translation of the proposed algorithm.

Environmental monitoring shows SARS-CoV-2 contamination of surfaces in food plants

The SARS-CoV-2 pandemic has presented new challenges to food manufacturers. In addition to preventing the spread of microbial contamination of food, with SARS-CoV-2, there is an additional focus on preventing SARS-CoV-2 infections in food plant personnel. During the early phase of the pandemic, several large outbreaks of Covid-19 occurred in food manufacturing plants resulting in deaths and economic loss. In March of 2020, we assisted in implementation of environmental monitoring programs for SARS-CoV-2 in 116 food production facilities. All participating facilities had already implemented measures to prevent symptomatic personnel from coming to work. During the study period, from March 17, 2020 to September 3, 2020, 1.23% of the 22,643 environmental samples tested positive for SARS-CoV-2, suggesting that infected individuals are actively shedding virus. Virus contamination was commonly found on frequently touched surfaces. Most plants managed to control their environmental contamination when they became aware of the positive findings. Comparisons of the personnel test results to environmental contamination in one plant showed a good correlation between the two. Our work illustrates that environmental monitoring for SARS-CoV-2 can be used as a surrogate for identifying the presence of asymptomatic and pre-symptomatic personnel in workplaces and may aid in controlling infection spread. HighlightsO_LIEnvironmental contamination by SARS-CoV-2 virus was detected in food plants C_LIO_LIOut of 22,643 environmental swabs, 278 (1.23%) were positive for SARS-CoV-2 C_LIO_LIFrequently touched surfaces had the most contamination C_LIO_LISurface testing for SARS-CoV-2 may indicate presence of asymptomatic carriers C_LI

A simplified cell-based assay to identify coronavirus 3CL protease inhibitors

We describe a mammalian cell-based assay capable of identifying coronavirus 3CL protease (3CLpro) inhibitors without requiring the use of live virus. By enabling the facile testing of compounds across a range of coronavirus 3CLpro enzymes, including the one from SARS-CoV-2, we are able to quickly identify compounds with broad or narrow spectra of activity. We further demonstrate the utility of our approach by performing a curated compound screen along with structure-activity profiling of a series of small molecules to identify compounds with antiviral activity. Throughout these studies, we observed concordance between data emerging from this assay and from live virus assays. By democratizing the testing of 3CL inhibitors to enable screening in the majority of laboratories rather than the few with extensive biosafety infrastructure, we hope to expedite the search for coronavirus 3CL protease inhibitors, to address the current epidemic and future ones that will inevitably arise.

Long-term Efficacy of S-1 Monotherapy or Capecitabine Plus Oxaliplatin as Adjuvant Chemotherapy for Patients with Stage II or III Gastric Cancer after Curative Gastrectomy: a Propensity Score-Matched Multicenter Cohort Study

Purpose@#To compare long-term disease-free survival (DFS) between patients receiving tegafur/gimeracil/oteracil (S-1) or capecitabine plus oxaliplatin (CAPOX) adjuvant chemotherapy (AC) for gastric cancer (GC). @*Materials and Methods@#This retrospective multicenter observational study enrolled 983 patients who underwent curative gastrectomy with consecutive AC with S-1 or CAPOX for stage II or III GC at 27 hospitals in Korea between February 2012 and December 2013. We conducted propensity score matching to reduce selection bias. Long-term oncologic outcomes, including DFS rate over 5 years (over-5yr DFS), were analyzed postoperatively. @*Results@#The median and longest follow-up period were 59.0 and 87.6 months, respectively. DFS rate did not differ between patients who received S-1 and CAPOX for pathologic stage II (P=0.677) and stage III (P=0.899) GC. Moreover, hazard ratio (HR) for recurrence did not differ significantly between S-1 and CAPOX (reference) in stage II (HR, 1.846; 95% confidence interval [CI], 0.693–4.919; P=0.220) and stage III (HR, 0.942; 95% CI, 0.664–1.337; P=0.738) GC. After adjustment for significance in multivariate analysis, pT (4 vs. 1) (HR, 11.667; 95% CI, 1.595–85.351; P=0.016), pN stage (0 vs. 3) (HR, 2.788; 95% CI, 1.502–5.174; P=0.001), and completion of planned chemotherapy (HR, 2.213; 95% CI, 1.618–3.028; P<0.001) were determined as independent prognostic factors for DFS. @*Conclusions@#S-1 and CAPOX AC regimens did not show significant difference in over-5yr DFS after curative gastrectomy in patients with stage II or III GC. The pT, pN stage, and completion of planned chemotherapy were prognostic factors for GC recurrence.

Erratum: A Validation Study of a Multiple Reaction Monitoring-Based Proteomic Assay to Diagnose Breast Cancer / 한국유방암학회지

In the article, “A Validation Study of a Multiple Reaction Monitoring-Based Proteomic Assay to Diagnose Breast Cancer” in Volume 22(4), page 579-586 was error in the table. In Table 1, the value of pN0 was incorrectly listed as 29 (56.9) in ‘diagnosed as normal by biomarker’ and corrected to 39 (76.5). The authors apologize for any inconvenience that this may have caused.

A Validation Study of a Multiple Reaction Monitoring-Based Proteomic Assay to Diagnose Breast Cancer / 한국유방암학회지

Who Can Perform Adjuvant Chemotherapy Treatment for Gastric Cancer? A Multicenter Retrospective Overview of the Current Status in Korea

PURPOSE: To investigate the current status of adjuvant chemotherapy (AC) regimens in Korea and the difference in efficacy of AC administered by surgical and medical oncologists in patients with stage II or III gastric cancers. MATERIALS AND METHODS: We performed a retrospective observational study among 1,049 patients who underwent curative resection and received AC for stage II and III gastric cancers between February 2012 and December 2013 at 29 tertiary referral university hospitals in Korea. To minimize the influence of potential confounders on selection bias, propensity score matching (PSM) was used based on binary logistic regression analysis. The 3-year disease-free survival (DFS) rates were compared between patients who received AC administered by medical oncologists or surgical oncologists. RESULTS: Between February 2012 and December 2013 in Korea, the most commonly prescribed AC by medical oncologists was tegafur/gimeracil/oteracil (S-1, 47.72%), followed by capecitabine with oxaliplatin (XELOX, 16.33%). After performing PSM, surgical oncologists (82.74%) completed AC as planned more often than medical oncologists (75.9%), with statistical significance (P=0.036). No difference in the 3-year DFS rates of stage II (P=0.567) or stage III (P=0.545) gastric cancer was found between the medical and surgical oncologist groups. CONCLUSIONS: S-1 monotherapy and XELOX are a main stay of AC, regardless of whether the prescribing physician is a medical or surgical oncologist. The better compliance with AC by surgical oncologists is a valid reason to advocate that surgical oncologists perform the treatment of AC for stage II or III gastric cancers.

Nationwide survey of partial fundoplication in Korea: comparison with total fundoplication

PURPOSE: Laparoscopic total fundoplication is the standard surgery for gastroesophageal reflux disease. However, partial fundoplication may be a viable alternative. Here, we conducted a nationwide survey of partial fundoplication in Korea. METHODS: The Korean Anti-Reflux Surgery study group recorded 32 cases of partial fundoplication at eight hospitals between September 2009 and January 2016. The surgical outcomes and postoperative adverse symptoms in these cases were evaluated and compared with 86 cases of total fundoplication. RESULTS: Anterior partial fundoplication was performed in 20 cases (62.5%) and posterior in 12 (37.5%). In most cases, partial fundoplication was a secondary procedure after operations for other conditions. Half of patients who underwent partial fundoplication had typical symptoms at the time of initial diagnosis, and most of them showed excellent (68.8%), good (25.0%), or fair (6.3%) symptom resolution at discharge. Compared to total fundoplication, partial fundoplication showed no difference in the resolution rate of typical and atypical symptoms. However, adverse symptoms such as dysphagia, difficult belching, gas bloating and flatulence were less common after partial fundoplication. CONCLUSION: Although antireflux surgery is not popular in Korea and total fundoplication is the primary surgical choice for gastroesophageal reflux disease, partial fundoplication may be useful in certain conditions because it has less postoperative adverse symptoms but similar efficacy to total fundoplication.

Outcome of Gastric Cancer Surgery in Elderly Patients

PURPOSE: Owing to increased life expectancy, the number of elderly patients with gastric cancer has increased. This study aimed to identify the outcomes of gastric cancer patients aged 80 years or older through comparison of their clinicopathological characteristics, surgical outcomes, and oncologic outcomes. MATERIALS AND METHODS: Between January 2006 and December 2013, the records of 478 patients who underwent surgery for gastric cancer were retrospectively evaluated. Patients were divided into two groups: patients <80 years old (n=446) and patients ≥80 years old (n=32). RESULTS: There were no significant differences in sex, body mass index, length of hospital stay, duration of surgery, depth of invasion, nodal metastasis, histologic type, or tumor size between the two groups. However, significant differences were found for the American Society of Anesthesiologist score and the serum albumin level between the two groups. Postoperative morbidity, mortality, disease-free survival, and recurrence rate did not differ between curatively resected patients in the two groups. CONCLUSIONS: In elderly patients with gastric cancer, active treatment including radical gastrectomy is necessary.

Clinical outcomes of subtotal cholecystectomy performed for difficult cholecystectomy

PURPOSE: Laparoscopic subtotal cholecystectomy (LSC) can be an alternative surgical technique for difficult cholecystectomies. Surgeons performing LSC sometimes leave the posterior wall of the gallbladder (GB) to shorten the operation time and avoid liver injury. However, leaving the inflamed posterior GB wall is a major concern. In this study, we evaluated the clinical outcomes of standard laparoscopic cholecystectomy (SLC), LSC, and LSC removing only anterior wall of the GB (LSCA). METHODS: We retrospectively reviewed the medical records of laparoscopic cholecystectomies performed between January 2006 to December 2015 and analyzed the outcomes of SLC, LSC, and LSCA. RESULTS: A total of 1,037 patients underwent SLC. 22 patients underwent LSC; and 27 patients underwent LSCA. The mean operating times of SLC, LSC, and LSCA were 41, 74, and 68 minutes, respectively (P < 0.01). Blood loss was 5, 45, and 33 mL (P < 0.05). The mean lengths of postoperative hospitalization were 3.4, 5.4, and 5.8 days. Complications occurred in 24 SLC patients (2.3%), 2 LSC patients (9%), and 1 LSCA patient (3.7%). There was no mortality among the LSC and LSCA patients. CONCLUSION: LSC and LSCA are safe and feasible alternatives for difficult cholecystectomies. These procedures help surgeons avoid bile duct injury and conversion to laparotomy. LSCA has the benefits of shorter operation time and less bleeding compared to LSC.

Analysis of patient-dropouts from the critical pathways for gastric cancer

PURPOSE: This study was designed to determine the factors affecting completion of critical pathway for elective gastrectomy. METHODS: Since 2008, a critical pathway has been applied for elective gastrectomy at Chosun University Hospital. We retrospectively analyzed 252 patients who underwent elective gastrectomies from January 2009 to April 2013. The completion rate was determined, and risk factors for patient dropout were examined. RESULTS: The completion rate of the critical pathway was 45.6% (115/252). Mean length of stay was 11.7 +/- 8.6 days (8-59 days). Readmission rates were 4.4% (11/252). Causes of failure for clinical pathway were systemic complications (21/137, 15.3%), intra-abdominal complications (44/137, 32.8%), patient factors (41/137, 29.9%), and wound complications (30/137, 21.9%). There were no significant differences between the two groups in age, sex, American Society of Anesthesiologists (ASA) score, operation time, readmission, and underlying disease (P > 0.05). Body mass index (P = 0.008) and pathologic stage (P = 0.001) were significantly different between the two groups. In multivariate analysis, the conventional approach (odds ratio, 2.0), and total gastrectomy (odds ratio, 5.3) were determined to be independent risk factors to drop the critical pathway. But there were no significant differences between total and distal gastrectomy groups in age, gender, underlying diseases, ASA score, readmission, operation time, and cause of dropout (P > 0.05). CONCLUSION: We concluded that total gastrectomy may not be suitable for the critical pathway. We suggest that the critical pathway for elective distal gastrectomy is divided 2 subgroups, according to the surgical approach.

Early Gastric Cancer with Neurofibroma Mimicking a Metastatic Node: A Case Report

Neurofibromas are benign tumors that originate from the peripheral nerves, including neurites and fibroblasts. Generally, a solitary neurofibroma is located in the skin and rarely in other places. A 72-year-old female suffered from epigastric discomfort for 2 months. Endoscopic findings showed an early gastric cancer type IIc at the antrum. Abdominal computed tomography revealed early gastric cancer with a 1.6 cm-sized metastatic node posterior to the duodenum. Laparoscopic assisted distal gastrectomy and retro-pancreatic dissection were performed uneventfully. Histological examination revealed gastric adenocarcinoma, invading the mucosa without nodal metastasis, and a neurofibroma. Herein, we present a case of a gastric cancer patient with a solitary retroperitoneal neurofibroma which mimicked a distant metastatic node.

Early Gastric Cancer with Neurofibroma Mimicking a Metastatic Node: A Case Report

Neurofibromas are benign tumors that originate from the peripheral nerves, including neurites and fibroblasts. Generally, a solitary neurofibroma is located in the skin and rarely in other places. A 72-year-old female suffered from epigastric discomfort for 2 months. Endoscopic findings showed an early gastric cancer type IIc at the antrum. Abdominal computed tomography revealed early gastric cancer with a 1.6 cm-sized metastatic node posterior to the duodenum. Laparoscopic assisted distal gastrectomy and retro-pancreatic dissection were performed uneventfully. Histological examination revealed gastric adenocarcinoma, invading the mucosa without nodal metastasis, and a neurofibroma. Herein, we present a case of a gastric cancer patient with a solitary retroperitoneal neurofibroma which mimicked a distant metastatic node.

Diagnostic imaging of malignant insulinoma in a dog / 대한수의학회지

Endocrine test data from a 13-year old intact female Maltese was indicative of the presence of an insulinoma, however ultrasonography identified a pancreatic mass only after 10 months after the first admission. Following identification of both pancreatic tumor and hepatic metastasis on computed tomography (CT), surgical excision of the mass was attempted. However, total excision failed because of tumor adhesion to adjacent large vessels. The pancreatic mass was monitored over the next 25 months via ultrasonography, CT, and positron emission tomography-computed tomography (PET-CT). Histopathological and immunohistochemical data confirmed the diagnosis of insulinoma with hepatic metastasis.

Ewing's Sarcoma of the Stomach; Rare Case of Ewing's Sarcoma and Suggestion of New Treatment Strategy

Ewing's sarcoma is a neoplasm of the undifferenciated small round cells, which generally affects the bone and deep soft tissues of children and adolescents. We present a case of gastric Ewing's sarcoma; a 35-year-old female who had no symptoms. While she was at a routine medical checkup, a protruding mass in her gastric antrum was incidentally found on esophagogastroduodenoscopy. Endoscopic ultrasonogram showed a submucosal mass on the same lesion and a laparosopic wedge resection was done. Pathologic gross findings showed a granular grape appearance tissue and histoloigc examination revealed a small round cell tumor with CD 99 immunoexpression positive. In general, a combined modality therapy for Ewing's sarcoma such as surgical resection with chemotherapy, is accepted as an effective method. However, this patient had no adjuvant chemotherapy after surgery and she has no recurrence for eleven months.

Ewing's Sarcoma of the Stomach; Rare Case of Ewing's Sarcoma and Suggestion of New Treatment Strategy

Ewing's sarcoma is a neoplasm of the undifferenciated small round cells, which generally affects the bone and deep soft tissues of children and adolescents. We present a case of gastric Ewing's sarcoma; a 35-year-old female who had no symptoms. While she was at a routine medical checkup, a protruding mass in her gastric antrum was incidentally found on esophagogastroduodenoscopy. Endoscopic ultrasonogram showed a submucosal mass on the same lesion and a laparosopic wedge resection was done. Pathologic gross findings showed a granular grape appearance tissue and histoloigc examination revealed a small round cell tumor with CD 99 immunoexpression positive. In general, a combined modality therapy for Ewing's sarcoma such as surgical resection with chemotherapy, is accepted as an effective method. However, this patient had no adjuvant chemotherapy after surgery and she has no recurrence for eleven months.

Consideration of Cardia Preserving Proximal Gastrectomy in Early Gastric Cancer of Upper Body for Prevention of Gastroesophageal Reflux Disease and Stenosis of Anastomosis Site

PURPOSE: The aim of this study is to evaluate the feasibility and safety of cardia preserving proximal gastrectomy, in early gastric cancer of the upper third. MATERIALS AND METHODS: A total of 10 patients were diagnosed with early gastric cancer of the upper third through endoscopic biopsy. The operation time, length of resection free margin, number of resected lymph nodes and postoperative complications, gastrointestinal symptoms, nutritional status, anastomotic stricture, and recurrence were examined. RESULTS: There were 5 males and 5 females. The mean age was 56.5+/-0.5 years. The mean operation time was 188.5+/-0.5 minutes (laparoscopic operation was 270 minutes). Nine patients were T1 stage (T2 : 1), and N stage was all N0. The mean number of resected lymph nodes was 25.2+/-0.5. The length of proximal resection free margin was 3.1+/-0.1 cm and distal was 3.7+/-0.1 cm. Early complications were surgical site infection (1), bleeding (1), and gastro-esophageal reflux disease (1) (this symptom was improved with medication). Late complications were dyspepsia (3) (this symptom was improved without any treatment), and others were nonspecific results of endoscopy or symptom. CONCLUSIONS: Cardia preserving proximal gastrectomy was feasible for early gastric cancer of the upper third. Further evaluation and prospective research will be required.

Clinical Effectiveness of Regular Use of Unripe Apple Mask Pack on Skin Status of Middle-aged Women

The effects of unripe apple mask pack made from unripe apple extracts on the skin status of middle-aged women for 4 weeks were investigated. The subjects were divided into three groups: placebo mask pack as the control (PM, n = 8), apple mask pack (AM, n = 16), and apple mask pack + apple intake (AAM, n = 12). The study included a survey questionnaire, and evaluations of nutrients intakes and of skin status. Skin status was measured by Aramo-TS. After 4 weeks, facial moisture, elasticity, evenness, and wrinkle level were improved in AM and AAM. The facial moisture level (AM: +3.13 +/- 2.73, AAM: +2.25 +/- 2.93) and elasticity level (AM: +5.81 +/- 8.27, AAM: +5.50 +/- 6.13) of AM (p < 0.001) and AAM (p < 0.05) were increased. The facial evenness level (AM: -5.25 +/- 8.13, AAM: -9.17 +/- 4.26) and wrinkle level (AM: -10.88 +/- 11.74, AAM: -17.83 +/- 12.22) were significantly decreased. AAM was more effective in improving skin elasticity, evenness, and wrinkle. The skin status of PM was not changed. While the macronutrient intakes of all the subjects were not different before and after the study, the daily intakes of some vitamins (vitamins B6, C, and E and folic acid) during the study were significantly increased in AAM. These findings suggested that regular use of apple mask pack was effective in improving overall skin status. Furthermore, the consumption of apples with mask pack application was much better in improving skin status.

Airway Responsiveness to Inhaled Aspirin is Influenced by Airway Hyperresponsiveness in Asthmatic Patients

BACKGROUND/AIMS: Many patients with aspirin-induced asthma have severe methacholine airway hyperresponsiveness (AHR), suggesting a relationship between aspirin and methacholine in airway response. This study was performed to determine whether methacholine AHR affects the response of asthmatics to inhaled aspirin. METHODS: The clinical records of 207 asthmatic patients who underwent inhalation challenges with both aspirin and methacholine were reviewed retrospectively. An oral aspirin challenge was performed in patients with a negative inhalation response. The bronchial reactivity index (BRindex) was calculated from the percent decrease in lung function divided by the last dose of the stimulus. RESULTS: Forty-one (20.9%) and 14 (7.1%) patients showed a positive response to aspirin following an inhalation and oral challenge, respectively. Only 24.3 and 14.3% of the responders had a history of aspirin intolerance, respectively. The methacholine BRindex was significantly higher in the inhalation responders (1.46 +/- 0.02) than in the oral responders (1.36 +/- 0.03, p < 0.01) and in non-responders (n = 141, 1.37 +/- 0.01, p < 0.001). The aspirin BRindex was significantly correlated with the methacholine BRindex (r = 0.270, p < 0.001). Three of four patients who received the oral challenge, despite a positive inhalation test, showed negative responses to the oral challenge. Two of these patients had severe AHR. CONCLUSIONS: A considerable number of asthmatic patients with no history of aspirin intolerance responded to the inhalation aspirin challenge. The airway response to aspirin was significantly correlated with methacholine-AHR, and a false-positive response to aspirin inhalation test seemed to occur primarily in patients with severe AHR.