Remnant Preservation of the Primary Vertical Graft in Revision Anterior Cruciate Ligament Reconstruction.

Background: The remnant preservation of a primary vertical graft in revision anterior cruciate ligament reconstruction (ACLR) can benefit anteroposterior stability. However, studies that address this concept are rare. Purpose: To evaluate clinical outcomes of remnant preservation of primary vertical graft in revision ACLR. Study Design: Cohort study; Level of evidence, 3. Methods: A total of 74 patients with revision ACLR were included in this retrospective study. Remnant preservation revision ACLR was performed only in patients with primary vertical grafts. The patients were divided into 2 groups according to whether the primary remnant vertical graft was preserved (remnant group; n = 48) or absent or sacrificed (no-remnant group; n = 26). The remnant group was further divided according to the degree of remnant tissue: sufficiently preserved subgroup (graft coverage, ≥50%; n = 25) and insufficiently preserved subgroup (graft coverage, <50%; n = 23). Clinical outcomes were evaluated using the International Knee Documentation Committee (IKDC) subjective form, Lysholm score, Tegner activity scale, manual laxity tests, and side-to-side difference in anterior tibial translation on Telos stress radiographs. Results: The mean time to final follow-up was 40.7 ± 16.8 months. The remnant group showed more improved results in the postoperative Lachman test and Telos side-to-side difference than did the no-remnant group (P = .017 and .016, respectively). The post hoc test revealed that the side-to-side difference in laxity in the sufficiently preserved subgroup significantly outperformed that in the no-remnant group (P = .001), although no significant difference existed between the insufficiently preserved and no-remnant subgroups (P = .850). The postoperative IKDC subjective form, Lysholm score, and Tegner activity scale did not show significant differences between the 2 groups (P = .480, .277, and .883, respectively). Conclusion: The remnant preservation of the primary vertical graft in revision ACLR may result in better anteroposterior stability. However, subjective outcomes in the remnant group did not exceed that of the no-remnant group. The subgroup analysis revealed that only sufficiently preserved remnants demonstrated better anteroposterior stability.

Potential of γ-Aminobutyric Acid-Producing Leuconostoc mesenteroides Strains Isolated from Kimchi as a Starter for High-γ-Aminobutyric Acid Kimchi Fermentation.

γ-Aminobutyric acid (GABA)-producing Leuconostoc mesenteroides K1501 and K1627, isolated from kimchi, exhibited the highest GABA production in 1% monosodium glutamic acid. Both strains showed high survival rates of approximately 87% in artificial gastric juice (pH 3.0) and >80% in 0.1% artificial bile salt fluid. The survival rate was approximately 28% in 0.3% artificial bile salt fluid and 0% in 0.5% artificial bile salts. Both strains showed excellent adhesion to intestinal epithelial cells (>99%). Furthermore, it was observed that growth was not inhibited at 2% salt concentration; however, it was slightly retarded at salt concentrations of 3% and 4%. Moreover, L. mesenteroides K1501 and K1627 inhibited the growth of certain species of Lactobacillus, whose presence in kimchi fermentation is undesirable. Therefore, L. mesenteroides K1501 and K1627 have the potential to be used as starter organisms for functional GABA-rich kimchi.

Direct-Acting Antivirals and the Risk of Hepatitis B Reactivation in Hepatitis B and C Co-Infected Patients: A Systematic Review and Meta-Analysis.

Hepatitis B (HBV) reactivation was observed to be more than 10% in patients receiving interferon-based therapy for hepatitis C (HCV) co-infection. At present, when direct-acting antiviral (DAA) has become the main treatment for HCV, there are few large-scale studies on the reactivation of HBV in these population. We studied HBV reactivation risk and prophylactic HBV treatment efficacy in HBV/HCV co-infected patients receiving DAA therapy. Relevant studies were selected from the Ovid-Medline, Ovid-EMBASE, Cochrane Central Register of Controlled Trials, KoreaMed, KMbase, and RISS databases through 4 September 2020. Data pooling was carried out using the random-effects method. We identified 39 articles with 119,484 patients with chronic (n = 1673) or resolved (n = 13,497) HBV infection under DAA therapy. When the studies were pooled, the HBV reactivation rate was 12% (95% confidence interval (CI) 6-19, I2 = 87%), indicating that this population needs careful attention. When stratified by baseline HBV DNA, the undetectable HBV DNA group showed a significantly lower risk of reactivation than the detectable HBV DNA group (odds ratio (OR) 0.30, 95% CI 0.11-0.86, I2 = 0%). Prophylactic HBV therapy reduced HBV reactivation risk (OR 0.25, 95% CI 0.07-0.92, I2 = 0%). Patients with a resolved HBV infection showed a negligible rate (0.4%) of HBV reactivation. In conclusion, patients with detectable HBV DNA levels warrant careful monitoring for HBV reactivation and may benefit from preventive anti-HBV treatment.

Primary hepatic sarcoidosis presenting with cholestatic liver disease and mimicking primary biliary cholangitis: a case report.

Sarcoidosis often involves the liver. However, primary hepatic sarcoidosis confined to the liver without evidence of systemic involvement is rare. We report the case of a 37-year-old man with hepatic sarcoidosis who initially presented with elevated liver enzymes and suspicious cirrhotic nodules on computed tomography. The patient had cirrhosis but did not have portal hypertension. Based on the initial histopathologic finding of chronic granulomatous inflammation and the common clinical characteristics of sarcoidosis, he was initially diagnosed with primary biliary cholangitis, and his daily dosage of ursodeoxycholic acid was increased to 900 mg. After 14 months of treatment, his total serum bilirubin concentration was 10.9 mg/dL (upper normal limit, 1.2 mg/dL). Additionally, a transjugular liver biopsy revealed multiple noncaseating granulomas. He was diagnosed with primary hepatic sarcoidosis involving the lungs, heart, spleen, kidneys, and skin. Treatment with methylprednisolone was initiated. Two weeks later, he was started on azathioprine, and the dose of steroid was simultaneously reduced. These findings indicate the importance of including hepatic sarcoidosis as a possible diagnosis in patients with elevated liver enzymes or cryptogenic cirrhosis.

Statin Supply and Polydrug Use in Older Adults: A Focus on Drug Combinations that Reduce Bone Density.

BACKGROUND: We investigated the comorbidities of individuals who were prescribed statins to identify the use of bone mineral density (BMD)-reducing drugs, examine polydrug use trends involving these drugs, and explore their relationship with osteoporosis. METHODS: We analyzed claims data from the Korean National Health Insurance Service (January 2014-December 2018). We sampled 20% of 8,379,419 patients aged ≥50 years who were prescribed statins. Among them, we analyzed the data of those who were administered two or more prescriptions for 14 days or longer within 6 months of the initial date of statin prescription. Data on comorbidities and drugs that can potentially reduce BMD were obtained. Osteoporosis-related diagnoses were obtained as an outcome measure. The relationship between statins and BMD-reducing drugs was analyzed using logistic regression. RESULTS: Among the 4,138 statin users aged 50 years or older, 552 were diagnosed with osteoporosis. The most common comorbidity in statin users was hypertension, followed by ischemic heart disease, diabetes mellitus, and stroke. The most frequently administered BMD-reducing drugs were proton pump inhibitors (PPIs). The osteoporosis diagnosis rate was higher in patients who were prescribed both statins and PPIs or both statins and levothyroxine than in those using only a statin. CONCLUSION: PPIs and levothyroxine should be prescribed cautiously in statin users and bone densitometry should be proactively performed considering the increased risk of osteoporosis.

The prognostic significance of tumor-infiltrating lymphocytes assessment with hematoxylin and eosin sections in resected primary lung adenocarcinoma.

The prognostic significance of tumor-infiltrating lymphocytes has been determined in cancers of the lung, colon and breast, though there is no standardized method for using this prognostic indicator for lung cancer. We applied a modified version of the method proposed by the International Immuno-Oncology Biomarkers Working Group to primary lung adenocarcinoma, which uses histologic findings of hematoxylin and eosin sections. The study included a total cohort of 146 lung adenocarcinoma patients who underwent lobectomy with lymph node dissection at two hospitals between 2008 and 2012. The full-face sections of hematoxylin and eosin-stained slides were reviewed, and we evaluated the level of tumor-infiltrating lymphocytes as a percentage of the area occupied out of the total intra-tumoral stromal area. Histopathologic factors include histologic grade, necrosis, extracellular mucin, lymphovascular invasion, lymph node metastasis, level of tumor infiltrating lymphocytes, tertiary lymphoid structures around the tumor, and the presence of a germinal center in tertiary lymphoid structures. The high level of tumor-infiltrating lymphocytes was found to be significantly correlated with the histologic grade (p = 0.023), necrosis (p = 0.042), abundance of tertiary lymphoid structures(p<0.001) and presence of a germinal center in tertiary lymphoid structures (p = 0.004). A high level of tumor-infiltrating lymphocytes was associated with better progression-free survival (p = 0.011) as well as overall survival (p = 0.049). On multivariable analysis, high tumor-infiltrating lymphocyte levels were a good independent prognostic factor for progression-free survival (Hazard ratio: 0.389, 95% confidence interval: 0.161-0.941, p = 0.036). Histologic evaluation of tumor-infiltrating lymphocytes level in lung adenocarcinoma with H&E sections therefore has prognostic value in routine surgical pathology.

Bronchoscopic management of solitary bronchial myelolipoma: a case report.

BACKGROUND: Myelolipoma is a rare benign tumor composed of mature adipose and hematopoietic tissues. Most myelolipomas are found in the adrenal glands, whereas intrathoracic myelolipoma is extremely rare. In particular, bronchial myelolipoma without the involvement of lung parenchyma has never been reported. CASE PRESENTATION: A previously healthy 38-year-old male developed dyspnea and a productive cough. Computed tomography revealed an endobronchial mass at the right bronchus intermedius and subsequent atelectasis of the right middle and lower lobes. Flexible bronchoscopy found a total obstruction of the right bronchus intermedius due to an endobronchial tumor. Using a rigid bronchoscope, the endobronchial tumor was resected and the base of the tumor was additionally ablated with a diode laser to prevent recurrence. The removed endobronchial tumor was a 13 mm × 20 mm-sized oval-shaped mass and was pathologically diagnosed as bronchial myelolipoma. Chest radiographs, obtained on the day following the procedure, showed an improvement of atelectasis, and accompanying symptoms were immediately improved. Follow-up bronchoscopy performed after 12 months evidenced no recurrence of the bronchial myelolipoma. CONCLUSIONS: We used bronchoscopic intervention in patients with solitary bronchial myelolipoma and there was no evidence of recurrence.

Thyrocyte-specific deletion of insulin and IGF-1 receptors induces papillary thyroid carcinoma-like lesions through EGFR pathway activation.

Insulin and insulin-like growth factor (IGF)-1 signaling in the thyroid are thought to be permissive for the coordinated regulation by thyroid-stimulating hormone (TSH) of thyrocyte proliferation and hormone production. However, the integrated role of insulin receptor (IR) and IGF-1 receptor (IGF-1R) in thyroid development and function has not been explored. Here, we generated thyrocyte-specific IR and IGF-1R double knockout (DTIRKO) mice to precisely evaluate the coordinated functions of these receptors in the thyroid of neonates and adults. Neonatal DTIRKO mice displayed smaller thyroids, paralleling defective folliculogenesis associated with repression of the thyroid-specific transcription factor Foxe1. By contrast, at postnatal day 14, absence of IR and IGF-1R paradoxically induced thyrocyte proliferation, which was mediated by mTOR-dependent signaling pathways. Furthermore, we found elevated production of TSH during the development of follicular hyperplasia at 8 weeks of age. By 50 weeks, all DTIRKO mice developed papillary thyroid carcinoma (PTC)-like lesions that correlated with induction of the ErbB pathway. Taken together, these data define a critical role for IR and IGF-1R in neonatal thyroid folliculogenesis. They also reveal an important reciprocal relationship between IR/IGF-1R and TSH/ErbB signaling in the pathogenesis of thyroid follicular hyperplasia and, possibly, of papillary carcinoma.

Long Cut Straw Provides Stable the Rates of Survival, Pregnancy and Live Birth for Vitrification of Human Blasotcysts.

Most of the commercial devices for vitrification are directly immersed into the warming solution (WS) for increasing of warming rate. However, the previous modified cut standard straw (MCS) which has reported is difficult to immerse into the WS. The aim of this study was to investigate whether the long cut straw (LCS) could be useful as a stable tool for vitrified-warmed human blastocysts. A total of 138 vitrified-warmed cycles were performed between November 2013 and November 2014 (exclusion criteria: women ≥38 years old, poor responder, surgical retrieval sperm, and severe male factor). The artificial shrinkage was conducted using 29-gauge needles. Ethylene glycol and dimethyl sulfoxide (7.5% and 15% (v/v)) were used as cryoprotectants. Freezing and warming were conducted using the LCS tool. The cap of LCS was removed using the forceps in the liquid nitrogen (LN2) and then directly immersed into the first WS for 1 min at 37℃ (1 M sucrose). Only re-expanded blastocysts were transferred after it was cultured in sequential media for 18-20 h. A total of 294 blastocysts were warmed, and all were recovered (100%). Two hundred eighty-five embryos were survived (96.9%). The vitrifiedwarmed blastocysts of all patients were transferred without any cancellation. We were able to achieve a reasonable implantation (24.2%), following by clinical pregnancy (36.2%), which then continued to ongoing pregnancy (36.2%), and live birth (31.2%). Using LCS is achieved the acceptable rates of survival, pregnancy and live birth. Therefore, the LCS could be considered as a stable and simple tool for human embryo vitrificaton.

Nodular Fasciitis of External Auditory Canal.

Nodular fasciitis is a pseudosarcomatous reactive process composed of fibroblasts and myofibroblasts, and it is most common in the upper extremities. Nodular fasciitis of the external auditory canal is rare. To the best of our knowledge, less than 20 cases have been reported to date. We present a case of nodular fasciitis arising in the cartilaginous part of the external auditory canal. A 19-year-old man complained of an auricular mass with pruritus. Computed tomography showed a 1.7 cm sized soft tissue mass in the right external auditory canal, and total excision was performed. Histologic examination revealed spindle or stellate cells proliferation in a fascicular and storiform pattern. Lymphoid cells and erythrocytes were intermixed with tumor cells. The stroma was myxoid to hyalinized with a few microcysts. The tumor cells were immunoreactive for smooth muscle actin, but not for desmin, caldesmon, CD34, S-100, anaplastic lymphoma kinase, and cytokeratin. The patient has been doing well during the 1 year follow-up period.

Deletion of IGF-1 Receptors in Cardiomyocytes Attenuates Cardiac Aging in Male Mice.

IGF-1 receptor (IGF-1R) signaling is implicated in cardiac hypertrophy and longevity. However, the role of IGF-1R in age-related cardiac remodeling is only partially understood. We therefore sought to determine whether the deletion of the IGF-1R in cardiomyocytes might delay the development of aging-associated myocardial pathologies by examining 2-year-old male cardiomyocyte-specific IGF-1R knockout (CIGF1RKO) mice. Aging was associated with the induction of IGF-1R expression in hearts. Cardiomyocytes hypertrophied with age in wild-type (WT) mice. In contrast, the cardiac hypertrophic response associated with aging was blunted in CIGF1RKO mice. Concomitantly, fibrosis was reduced in aged CIGF1RKO compared with aged WT hearts. Expression of proinflammatory cytokines such as IL-1α, IL-1ß, IL-6, and receptor activator of nuclear factor-κB ligand was increased in aged WT hearts, but this increase was attenuated in aged CIGF1RKO hearts. Phosphorylation of Akt was increased in aged WT, but not in aged CIGF1RKO, hearts. In cultured cardiomyocytes, IGF-1 induced senescence as demonstrated by increased senescence-associated ß-galactosidase staining, and a phosphoinositide 3-kinase inhibitor inhibited this effect. Furthermore, inhibition of phosphoinositide 3-kinase significantly prevented the increase in IL-1α, IL-1ß, receptor activator of nuclear factor-κB ligand, and p21 protein expression by IGF-1. These data reveal an essential role for the IGF-1-IGF-1R-Akt pathway in mediating cardiomyocyte senescence.

Combined use of basal insulin analog and acarbose reduces postprandial glucose in patients with uncontrolled type 2 diabetes.

AIMS/INTRODUCTION: Early initiation of basal insulin therapy is recommended for normalizing fasting blood glucose in type 2 diabetes mellitus. However, basal insulin treatment might not adequately control postprandial glucose levels. The present study evaluated whether the combination of the α-glucosidase inhibitor, acarbose, and basal insulin improved blood glucose control under daily-life treatment conditions in a large sample of Korean patients. MATERIALS AND METHODS: The present study was a multicenter, prospective, observational study under daily-life treatment conditions. A total of 539 patients with type 2 diabetes who were treated with basal insulin and additional acarbose were enrolled and followed up for 20 weeks. Changes in hemoglobin A1c, fasting and postprandial blood glucose were evaluated at baseline and at the end of the observation period. The physician and patient satisfaction of the combination treatment and safety were assessed. RESULTS: Hemoglobin A1c decreased by 0.55 ± 1.05% from baseline (P < 0.0001). Fasting and postprandial blood glucose levels were reduced by 0.89 ± 3.79 and 2.59 ± 4.77 mmol/L (both P < 0.0001). The most frequently reported adverse drug reactions were flatulence (0.37%) and abnormal gastrointestinal sounds (0.37%), and all were mild in intensity and transient. In the satisfaction evaluation, 79.0% of physicians and 77.3% of patients were 'very satisfied' or 'satisfied' with the combined basal insulin and acarbose therapy. CONCLUSIONS: Combination therapy of basal insulin and acarbose in patients with type 2 diabetes improved glucose control, and had no drug-specific safety concerns, suggesting that the treatment might benefit individuals who cannot control blood glucose with basal insulin alone.

Arthroscopic repair of horizontal meniscal cleavage tears with marrow-stimulating technique.

PURPOSE: The purpose of this study was to evaluate patients after arthroscopic repair of meniscal horizontal tears with a marrow-stimulating technique through clinical signs and second-look arthroscopy. METHODS: We retrospectively reviewed a consecutive series of 32 meniscal repairs with horizontal cleavage tears and evaluated them through clinical assessment and second-look arthroscopic examinations. Arthroscopic meniscal repair and a marrow-stimulating technique were performed. Functional outcomes were evaluated using the visual analog scale (VAS) pain score, Lysholm knee scoring scale, and Tegner activity scale. Assessment of meniscal healing was evaluated clinically by the presence of meniscal signs; second-look arthroscopy was performed in 11 patients. Correlation between chronicity of a meniscal lesion (time from initial symptom [TFIS]) and meniscal healing was evaluated. RESULTS: The mean follow-up period was 45.6 ± 13.9 months. Improvements in mean VAS scores from 6.7 to 1.9 (P < .001) were observed. The Lysholm score increased from 48.0 ± 14.4 to 92.0 ± 6.3 (P < .001). The Tegner activity score increased from 3.3 ± 1.1 to 6.8 ± 0.8 (P < .001). At the last follow-up, 29 of 32 patients (91%) were evaluated as healing in the clinical assessment. Of the 11 patients who underwent second-look arthroscopy, 8 (73%) showed complete healing, 2 (18%) had incomplete healing, and 1 (9%) failed to heal. Correlation between TFIS and meniscal healing was clinically significant (P = .001) but arthroscopically insignificant (P = .085) on second-look arthroscopy. CONCLUSIONS: The meniscal repair procedure for horizontal cleavage tears in the present study suggests an alternative treatment option to approach the treatment of meniscal tears extending into the avascular zone and degenerative tissue. The marrow-stimulating technique using a cannulated reamer can be considered as an alternative method for the augmentation of meniscal healing. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

IGF-1 receptor deficiency in thyrocytes impairs thyroid hormone secretion and completely inhibits TSH-stimulated goiter.

Although thyroid-stimulating hormone (TSH) is known to be a major regulator of thyroid hormone biosynthesis and thyroid growth, insulin-like growth factor 1 (IGF-1) is required for mediating thyrocyte growth in concert with TSH in vitro. We generated mice with thyrocyte-selective ablation of IGF-1 receptor (TIGF1RKO) to explore the role of IGF-1 receptor signaling on thyroid function and growth. In 5-wk-old TIGF1RKO mice, serum thyroxine (T4) concentrations were decreased by 30% in concert with a 43% down-regulation of the monocarboxylate transporter 8 (MCT8), which is involved in T4 secretion. Despite a 3.5-fold increase in circulating concentrations of TSH, thyroid architecture and size were normal. Furthermore, thyrocyte area was increased by 40% in WT thyroids after 10 d TSH injection, but this effect was absent in TSH-injected TIGF1RKO mice. WT mice treated with methimazole and sodium perchlorate for 2 or 6 wk exhibited pronounced goiter development (2.0 and 5.4-fold, respectively), but in TIGF1RKO mice, goiter development was completely abrogated. These data reveal an essential role for IGF-1 receptor signaling in the regulation of thyroid function and TSH-stimulated goitrogenesis.

Reliability and validity of a self-reported measure of medication adherence in patients with type 2 diabetes mellitus in Korea.

OBJECTIVE: This study examined the psychometric properties of the Korean version of the eight-item Morisky Medication Adherence Scale (MMAS-8) to measure adherence to diabetes medication in patients with type 2 diabetes mellitus. METHODS: The English version of the MMAS-8 was translated into Korean and administered to patient with type 2 diabetes mellitus via face-to-face interviews, conducted by an independent interviewer. Patient characteristics and glycosylated haemoglobin (HbA1c) levels were assessed at the same clinic visit. A proportion of patients was randomly selected for 2-week test-retest reliability via telephone interviews. Convergent validity of the MMAS-8 against a four-item MMAS, correlations with HbA1c levels and construct validity of the MMAS-8 were evaluated. RESULTS: In total, 317 patients were included; 70 completed the 2-week test-retest interview. Internal consistency reliability was moderate and test-retest reliability of the MMAS-8 was excellent, although a ceiling effect was detected. Good convergent validity was shown by the high correlation of the new scale scores with the original MMAS-4. A significant association was found between MMAS-8 scores and HbA1c levels. Using glycaemic control as a gold standard, sensitivity was 74.1% and specificity was 38.3%. Explanatory factor analysis identified three dimensions of the scale. CONCLUSIONS: In light of acceptable reliability and validity, the MMAS-8 is a simple and quick method for the assessment of medication adherence among patient with type 2 diabetes mellitus, in a busy clinic setting.

Nutritional status and cardiac autophagy.

Autophagy is necessary for the degradation of long-lasting proteins and nonfunctional organelles, and is activated to promote cellular survival. However, overactivation of autophagy may deplete essential molecules and organelles responsible for cellular survival. Lifelong calorie restriction by 40% has been shown to increase the cardiac expression of autophagic markers, which suggests that it may have a cardioprotective effect by decreasing oxidative damage brought on by aging and cardiovascular diseases. Although cardiac autophagy is critical to regulating protein quality and maintaining cellular function and survival, increased or excessive autophagy may have deleterious effects on the heart under some circumstances, including pressure overload-induced heart failure. The importance of autophagy has been shown in nutrient supply and preservation of energy in times of limitation, such as ischemia. Some studies have suggested that a transition from obesity to metabolic syndrome may involve progressive changes in myocardial inflammation, mitochondrial dysfunction, fibrosis, apoptosis, and myocardial autophagy.

A case of teriparatide on pregnancy-induced osteoporosis.

Pregnancy-induced osteoporosis is a rare disorder characterized by fragility fracture and low bone mineral density (BMD) during or shortly after pregnancy, and its etiology is still unclear. We experienced a case of a 39-year-old woman who suffered from lumbago 3 months after delivery. Biochemical evidence of increased bone resorption is observed without secondary causes of osteoporosis. Radiologic examination showed multiple compression fractures on her lumbar vertebrae. We report a case of patient with pregnancy-induced osteoporosis improved her clinical symptom, BMD and bone turnover marker after teriparatide therapy.

Mechanisms and consequences of inflammatory signaling in the myocardium.

To further understand chronic heart disease, such as heart failure and cardiomyopathy, we must fully define signaling pathways within the myocardium. Recent studies suggest that some forms of heart disease are associated with a chronic low-grade inflammation that promotes adverse ventricular remodeling and correlates with disease progression. Several inflammatory mediators, including TNF-α, IL-1ß, and IL-6, are involved in cardiac injury subsequent to myocardial ischemia and reperfusion, sepsis, viral myocarditis, and transplant rejection. Once activated, components of the inflammatory response can have both beneficial and deleterious effects on the heart. In this review, we discuss the complex inflammatory signaling pathways in the myocardium and potential therapeutic implications.