Objective: Primary frozen shoulder causes significant pain and progressively restricts shoulder movements. Diagnosis is made clinically based on patient history and physical examination. Management is mainly non-invasive owing to its self-limiting clinical course. However, clinical practice guidelines for frozen shoulder have not yet been developed in Korea. The developed guidelines aim to provide evidence-based recommendations for the diagnosis and treatment of frozen shoulder. Methods: A guideline development committee reviewed the literature from four databases (PubMed, Embase, Cochrane Library, and KMbase). Using the Population, Intervention, Comparator, and Outcome (PICO) framework, the committee formulated two backgrounds and 16 key questions to address common clinical concerns. Recommendations were made using the Grading of Recommendations, Assessment, Development, and Evaluation framework. Results: Diabetes, thyroid disease, and dyslipidemia significantly increase the risk of developing a frozen shoulder. Although frozen shoulder is often self-limiting, some patients may experience long-term functional disabilities. Ultrasound and magnetic resonance imaging should be used as adjunctive tools alongside clinical diagnosis, and rather than as independent diagnostic methods. Noninvasive approaches, such as medications, physical modalities, exercises, electrical stimulation, and manual therapy, may reduce pain and improve shoulder function. Other noninvasive interventions have limited evidence, and their application should be based on clinical judgment. Intra-articular steroid injections are recommended for treatment, and physiotherapy or hydrodilation with steroid injections can also be beneficial. Conclusion These guidelines provide evidence-based recommendations for diagnosing and treating primary frozen shoulder.

Background: Genetically immunodeficient mice lacking Il2rg and Rag2 genes have been widely utilized in the field of biomedical research. However, immunodeficient rats, which offer the advantage of larger size, have not been as extensively used to date. Recently, Severe Combined Immunodeficiency (SCID) rats were generated using CRISPR/ Cas9 system, targeting Il2rg and Rag2 in National BioResource Project in Japan. We imported and investigated more detailed phenotypes of wild-type (WT) Il2rg knockout (KO), Rag2 KO and Il2rg/Rag2 KO rats for 20 weeks. Results: During experiments, Il2rg KO, Rag2 KO and Il2rg/Rag2 KO rats showed decreased white blood cells and sys‑ temic lymphopenia, with reduced CD4+, CD8+ T cells and CD161+ NK cells. Additionally, all KO strains exhibited reduced relative spleen weights, hypoplasia of the germinal center in the white pulp, and atrophy with the disap‑ pearance of the boundary between the cortex and medulla in the thymus, compared to WT rats. Furthermore, we established human acute lymphoblastic leukemia xenograft rat model by intravenously injecting 5.0 × ­106 cells/kg of NALM6 cells into Il2rg/Rag2 KO rats. Conclusions These findings indicate that Il2rg KO, Rag2 KO, and Il2rg/Rag2 KO rats exhibited SCID phenotypes, sug‑ gesting their potential application as immunodeficient animal models for tumor xenograft studies.

Background: Lac color, a natural red dye derived from the larvae of laccifer lacca kerr, is one of the most commonly used substances in food. To date, no studies have reported on the antigenicity of lac color and the other biomarkers that can determine anaphylactic reactions. To address this, we evaluated the antigenicity of lac color through active systemic anaphylaxis (ASA) in addition to identifying potential biomarkers performing exploratory studies. For ASA test, Guinea pigs (n = 5) were sensitized with 0(negative control), 4 mg/kg of lac color, 4 mg/kg of lac color + FCA, and 5 mg/kg of ovalbumin + FCA (positive control) 3 times a week for three weeks. Fourteen days after the last sensi‑ tization, animals were challenged intravenously weekly for two weeks. Hematological and histopathological analyses were performed and compared to control groups. Results: In the ASA test, all lac color groups showed mild symptoms such as nose rubbing, urination, and evacuation, which are insufficient indicators of anaphylaxis. Exploratory studies identified several biomarkers: decreased platelet count, and increased basophil count; distention in the lung, and redness on the inner wall of trachea; mononuclear inflammatory cell infiltration (MICI) in the ear, and heart hemorrhage. When these biomarkers were applied to the ASA test of lac color, in comparison to the negative control group, the positive control group (ovalbumin + FCA) showed a significant over 60-fold reduction in platelet count and nearly threefold higher basophil count compared to other groups. Furthermore, only positive control group exhibited full lung distention and severe redness on the inner wall of the trachea. Mononuclear inflammatory cell infiltration (MICI) in the ear was about three times higher, and heart hemorrhage was only present in the positive control group compared to others. None of the lac color groups were different from the negative control group (p > 0.05), whereas the positive control group was significantly different (p < 0.05). Conclusions Our study concludes that lac color, at the tested concentrations, does not induce antigenicity in the guinea pig model, providing valuable safety data. Furthermore, the biomarkers identified in this study offer a supportive approach to evaluating the immunogenicity of substances in future research.

Objective: This study aimed to compare the accuracy of robotic spine surgery and conventional pedicle screw fixation in lumbar degenerative disease. We evaluated clinical and radiological outcomes to demonstrate the noninferiority of robotic surgery. Methods: This study employed propensity score matching and included 3 groups: robot-assisted mini-open posterior lumbar interbody fusion (PLIF) (robotic surgery, RS), c-arm guided minimally invasive surgery transforaminal lumbar interbody fusion (C-arm guidance, CG), and freehand open PLIF (free of guidance, FG) (54 patients each). The mean follow-up period was 2.2 years. The preoperative spine condition was considered. Accuracy was evaluated using the Gertzbein-Robbins scale (GRS score) and Babu classification (Babu score). Radiological outcomes included adjacent segmental disease (ASD) and mechanical failure. Clinical outcomes were assessed based on the visual analogue scale, Oswestry Disability Index, 36-item Short Form health survey, and clinical ASD rate. Results: Accuracy was higher in the RS group (p < 0.01) than in other groups. The GRS score was lower in the CG group, whereas the Babu score was lower in the FG group compared with the RS group. No significant differences were observed in radiological and clinical outcomes among the 3 groups. Regression analysis identified preoperative facet degeneration, GRS and Babu scores as significant variables for radiological and clinical ASD. Mechanical failure was influenced by the GRS score and patients’ age. Conclusion This study showed the superior accuracy of robotic spine surgery compared with conventional techniques. When combined with minimally invasive surgery, robotic surgery is advantageous with reduced ligament and muscle damage associated with traditional open procedures.

Purpose: This study was performed to examine the ultrasonography (US) features of normal parathyroid glands (PTGs) that were identified on preoperative US and subsequently confirmed during thyroid surgery. Methods: This retrospective study included a consecutive sample of 161 patients (mean±standard deviation age, 56±14 years; 128 women) with 294 normal PTGs identified on preoperative US PTG mapping and confirmed during thyroidectomy. A presumed normal PTG on US was defined as a small, round to oval, hyperechoic structure in the central neck. These presumed normal PTGs, as identified on preoperative US, were mapped onto thyroid computed tomography images and diagrams of the thyroid gland and neck. During the preoperative real-time US examinations, the location, size, shape, echogenicity, echotexture, and intraglandular vascular flow of the identified presumed PTGs were assessed. These characteristics were compared between superior and inferior PTGs using the generalized estimating equation method. Results: The typical US features of homogeneous hyperechogenicity without intraglandular vascular flow were observed in 267 (90.8%) normal PTGs, while atypical features, including isoechogenicity (1.0%), heterogeneous echotexture with focal hypoechogenicity (5.8%), and intraglandular vascular flow (3.7%), were noted in 27 (9.2%). Inferior PTGs were more frequently identified in posterolateral (36.1% vs. 5.3%) and thyroid pole locations (29.9% vs. 5.3%), and less frequently in posteromedial locations (29.2% vs. 88.0%), compared to superior PTGs (P<0.001 for each comparison). Conclusion Most normal PTGs displayed the typical US features of homogeneous hyperechogenicity without intraglandular vascular flow. However, in rare cases, normal PTGs exhibited atypical features, including isoechogenicity, heterogeneous echotexture with focal hypoechogenicity, and intraglandular vascular flow.

Purpose: This study was performed to examine the ultrasonography (US) features of normal parathyroid glands (PTGs) that were identified on preoperative US and subsequently confirmed during thyroid surgery. Methods: This retrospective study included a consecutive sample of 161 patients (mean±standard deviation age, 56±14 years; 128 women) with 294 normal PTGs identified on preoperative US PTG mapping and confirmed during thyroidectomy. A presumed normal PTG on US was defined as a small, round to oval, hyperechoic structure in the central neck. These presumed normal PTGs, as identified on preoperative US, were mapped onto thyroid computed tomography images and diagrams of the thyroid gland and neck. During the preoperative real-time US examinations, the location, size, shape, echogenicity, echotexture, and intraglandular vascular flow of the identified presumed PTGs were assessed. These characteristics were compared between superior and inferior PTGs using the generalized estimating equation method. Results: The typical US features of homogeneous hyperechogenicity without intraglandular vascular flow were observed in 267 (90.8%) normal PTGs, while atypical features, including isoechogenicity (1.0%), heterogeneous echotexture with focal hypoechogenicity (5.8%), and intraglandular vascular flow (3.7%), were noted in 27 (9.2%). Inferior PTGs were more frequently identified in posterolateral (36.1% vs. 5.3%) and thyroid pole locations (29.9% vs. 5.3%), and less frequently in posteromedial locations (29.2% vs. 88.0%), compared to superior PTGs (P<0.001 for each comparison). Conclusion Most normal PTGs displayed the typical US features of homogeneous hyperechogenicity without intraglandular vascular flow. However, in rare cases, normal PTGs exhibited atypical features, including isoechogenicity, heterogeneous echotexture with focal hypoechogenicity, and intraglandular vascular flow.

Background and Objectives: The popliteal artery is generally regarded as a “no-stent zone.”Limited data are available on the outcomes of drug-coated balloons (DCBs) for popliteal artery disease. This study aimed to evaluate the 12-month clinical outcomes among patients who received DCB treatment for atherosclerotic popliteal artery disease. Methods: This prospective, multicenter registry study enrolled 100 patients from 7 Korean endovascular centers who underwent endovascular therapy using IN.PACT DCB (Medtronic) for symptomatic atherosclerotic popliteal artery disease. The primary endpoint was 12-month clinical primary patency and the secondary endpoint was clinically driven target lesion revascularization (TLR)–free rate. Results: The mean age of the study cohort was 65.7±10.8 years, and 77% of enrolled patients were men. The mean lesion length was 93.7±53.7 mm, and total occlusions were present in 45% of patients. Technical success was achieved in all patients. Combined atherectomy was performed in 17% and provisional stenting was required in 11%. Out of the enrolled patients, 91 patients completed the 12-month follow-up. Clinical primary patency and TLR-free survival rates at 12 months were 76.0% and 87.2%, respectively. A multivariate Cox regression analysis identified female and longer lesion length as the significant independent predictors of loss of patency. Conclusions DCB treatment yielded favorable 12-month clinical primary patency and TLRfree survival outcomes in patients with popliteal artery disease.

Background: Genetically immunodeficient mice lacking Il2rg and Rag2 genes have been widely utilized in the field of biomedical research. However, immunodeficient rats, which offer the advantage of larger size, have not been as extensively used to date. Recently, Severe Combined Immunodeficiency (SCID) rats were generated using CRISPR/ Cas9 system, targeting Il2rg and Rag2 in National BioResource Project in Japan. We imported and investigated more detailed phenotypes of wild-type (WT) Il2rg knockout (KO), Rag2 KO and Il2rg/Rag2 KO rats for 20 weeks. Results: During experiments, Il2rg KO, Rag2 KO and Il2rg/Rag2 KO rats showed decreased white blood cells and sys‑ temic lymphopenia, with reduced CD4+, CD8+ T cells and CD161+ NK cells. Additionally, all KO strains exhibited reduced relative spleen weights, hypoplasia of the germinal center in the white pulp, and atrophy with the disap‑ pearance of the boundary between the cortex and medulla in the thymus, compared to WT rats. Furthermore, we established human acute lymphoblastic leukemia xenograft rat model by intravenously injecting 5.0 × ­106 cells/kg of NALM6 cells into Il2rg/Rag2 KO rats. Conclusions These findings indicate that Il2rg KO, Rag2 KO, and Il2rg/Rag2 KO rats exhibited SCID phenotypes, sug‑ gesting their potential application as immunodeficient animal models for tumor xenograft studies.

Background: Lac color, a natural red dye derived from the larvae of laccifer lacca kerr, is one of the most commonly used substances in food. To date, no studies have reported on the antigenicity of lac color and the other biomarkers that can determine anaphylactic reactions. To address this, we evaluated the antigenicity of lac color through active systemic anaphylaxis (ASA) in addition to identifying potential biomarkers performing exploratory studies. For ASA test, Guinea pigs (n = 5) were sensitized with 0(negative control), 4 mg/kg of lac color, 4 mg/kg of lac color + FCA, and 5 mg/kg of ovalbumin + FCA (positive control) 3 times a week for three weeks. Fourteen days after the last sensi‑ tization, animals were challenged intravenously weekly for two weeks. Hematological and histopathological analyses were performed and compared to control groups. Results: In the ASA test, all lac color groups showed mild symptoms such as nose rubbing, urination, and evacuation, which are insufficient indicators of anaphylaxis. Exploratory studies identified several biomarkers: decreased platelet count, and increased basophil count; distention in the lung, and redness on the inner wall of trachea; mononuclear inflammatory cell infiltration (MICI) in the ear, and heart hemorrhage. When these biomarkers were applied to the ASA test of lac color, in comparison to the negative control group, the positive control group (ovalbumin + FCA) showed a significant over 60-fold reduction in platelet count and nearly threefold higher basophil count compared to other groups. Furthermore, only positive control group exhibited full lung distention and severe redness on the inner wall of the trachea. Mononuclear inflammatory cell infiltration (MICI) in the ear was about three times higher, and heart hemorrhage was only present in the positive control group compared to others. None of the lac color groups were different from the negative control group (p > 0.05), whereas the positive control group was significantly different (p < 0.05). Conclusions Our study concludes that lac color, at the tested concentrations, does not induce antigenicity in the guinea pig model, providing valuable safety data. Furthermore, the biomarkers identified in this study offer a supportive approach to evaluating the immunogenicity of substances in future research.

Objective: This study aimed to compare the accuracy of robotic spine surgery and conventional pedicle screw fixation in lumbar degenerative disease. We evaluated clinical and radiological outcomes to demonstrate the noninferiority of robotic surgery. Methods: This study employed propensity score matching and included 3 groups: robot-assisted mini-open posterior lumbar interbody fusion (PLIF) (robotic surgery, RS), c-arm guided minimally invasive surgery transforaminal lumbar interbody fusion (C-arm guidance, CG), and freehand open PLIF (free of guidance, FG) (54 patients each). The mean follow-up period was 2.2 years. The preoperative spine condition was considered. Accuracy was evaluated using the Gertzbein-Robbins scale (GRS score) and Babu classification (Babu score). Radiological outcomes included adjacent segmental disease (ASD) and mechanical failure. Clinical outcomes were assessed based on the visual analogue scale, Oswestry Disability Index, 36-item Short Form health survey, and clinical ASD rate. Results: Accuracy was higher in the RS group (p < 0.01) than in other groups. The GRS score was lower in the CG group, whereas the Babu score was lower in the FG group compared with the RS group. No significant differences were observed in radiological and clinical outcomes among the 3 groups. Regression analysis identified preoperative facet degeneration, GRS and Babu scores as significant variables for radiological and clinical ASD. Mechanical failure was influenced by the GRS score and patients’ age. Conclusion This study showed the superior accuracy of robotic spine surgery compared with conventional techniques. When combined with minimally invasive surgery, robotic surgery is advantageous with reduced ligament and muscle damage associated with traditional open procedures.