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The analysis and review of the thermal decomposition properties required for the fire spread simulation of cables composed of multiple materials were performed. Thus, a typical two-step pyrolysis reaction was identified independent of cable type. It is expected that the Kissinger and flynn–wall–ozawa (FWO) methods, which are calculated using various heating rates, more accurately predict fire spread than the input method that uses the and values calculated using a single heating rate. Consequently, in the case of flame-retardant cables (CLASS 1E and TFR-8), the Kissinger method is more likely to overestimate the fire spread rate than the FWO method. In the case of polyvinyl chloride (PVC) cables (vinyl cabtire power cable, VCTF), the fire spread rate may be underestimated.

BACKGROUND Measurement of sodium intake in hospitalized patients is critical for their care. In this study, artificial intelligence (AI)-based imaging was performed to determine sodium intake in these patients. OBJECTIVE The applicability of a diet management system was evaluated using AI-based imaging to assess the sodium content of diets prescribed for hospitalized patients. METHODS Based on the information on the already investigated nutrients and quantity of food, consumed sodium was analyzed through photographs obtained before and after a meal. You only look once (YOLO v4)-based models and convolutional neural networks, including ResNet-101, were used to classify food and dish areas as well as food quantity, respectively. The 24-h urine sodium (UNa) value was measured as a reference for evaluating the sodium intake. RESULTS Among the 54 people enrolled, 25 participants with full data were analyzed. The results revealed that the median sodium intake calculated by the AI algorithm (AI-Na) was 2022.7 mg per day/person (adjusted by administered fluids). Although the 24-h UNa revealed a significant relationship with AI-Na along with the estimated glomerular filtration rate, the AI-Na calculations and 24-h UNa measurements differed considerably. Finally, a formula was derived using regression with an interaction term considering patients’ characteristics, such as sex, age, renal function, the use of diuretics, and administered fluids; thus, AI-Na has clinical significance in the calculation of salt intake in hospitalized patients using images without measuring 24-h UNa. Furthermore, we estimated that AI-Na corresponds to the 24-h UNa, dependent on a factor of 2.355 in the diuretics group and 0.353 in the non-diuretics group, indicating that the use of diuretics affects sodium excretion. CONCLUSIONS This study highlights the potential of AI-based imaging for determining sodium intake in hospitalized patients.

The differentiation of naive CD8+ T cells into effector cells is important for establishing immunity. However, the effect of heterogeneous naive CD8+ T cell populations is not fully understood. Here, we demonstrate that steady-state naive CD8+ T cells are composed of functionally heterogeneous subpopulations that differ in their ability to differentiate into type 17 cytotoxic effector cells (Tc17) in inflammatory disease models. The differential ability of Tc17 differentiation was not related to T-cell receptor (TCR) diversity and antigen specificity but was inversely correlated with self-reactivity acquired during development. Mechanistically, this phenomenon was linked to differential levels of intrinsic TCR sensitivity and basal SMAD3 expression, generating a wide spectrum of Tc17 differentiation potential within naive CD8+ T cell populations. These findings suggest that developmental self-reactivity can determine the fate of naive CD8+ T cells to generate functionally distinct effector populations and achieve immense diversity and complexity in antigen-specific T-cell immune responses.

Background: No consensus exists regarding the early use of subcutaneous (SC) basal insulin facilitating the transition from continuous intravenous insulin infusion (CIII) to multiple SC insulin injections in patients with severe hyperglycemia other than diabetic ketoacidosis. This study evaluated the effect of early co-administration of SC basal insulin with CIII on glucose control in patients with severe hyperglycemia.Methods: Patients who received CIII for the management of severe hyperglycemia were divided into two groups: the early basal insulin group (n=86) if they received the first SC basal insulin 0.25 U/kg body weight within 24 hours of CIII initiation and ≥4 hours before discontinuation, and the delayed basal insulin group (n=79) if they were not classified as the early basal insulin group. Rebound hyperglycemia was defined as blood glucose level of >250 mg/dL in 24 hours following CIII discontinuation. Propensity score matching (PSM) methods were additionally employed for adjusting the confounding factors (n=108).Results: The rebound hyperglycemia incidence was significantly lower in the early basal insulin group than in the delayed basal insulin group (54.7% vs. 86.1%), despite using PSM methods (51.9%, 85.2%). The length of hospital stay was shorter in the early basal insulin group than in the delayed basal insulin group (8.5 days vs. 9.6 days, P=0.027). The hypoglycemia incidence did not differ between the groups.Conclusion: Early co-administration of basal insulin with CIII prevents rebound hyperglycemia and shorten hospital stay without increasing the hypoglycemic events in patients with severe hyperglycemia.

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We recruited 50 patients with unresectable stage III NSCLC who received CCRT between March 2020 and March 2021. Durvalumab consolidation (DC) was administered to patients (n = 23) without progression after CCRT and programmed death-ligand 1 (PD-L1) ≥ 1%. Blood samples were collected before (C0) and after CCRT (C1) to calculate PBC counts and analyze CTCs. CTCs, isolated by the CD-PRIMETM system, exhibited EpCAM/CK+/CD45− phenotype in BioViewCCBSTM. At median follow-up of 27.4 months, patients with residual CTC clusters at C1 had worse median PFS than those without a detectable CTC cluster (11.0 vs. 27.8 months, p = 0.032), and this trend was noted only in the DC group (p = 0.034). Patients with high platelets at C1 (PLThi, >252 × 103/µL) had worse median PFS than those with low platelets (PLTlo) (5.9 vs. 17.1 months, p < 0.001). In multivariable analysis, PLThi and residual CTC clusters at C1 were independent risk factors for PFS, and DC group with PLThi and residual CTC clusters at C1 showed the worst median PFS (2.6 months, HR 45.16, p = 0.001), even worse than that of the CCRT alone group with PLThi (5.9 months, HR 15.39, p = 0.001). The comprehensive analysis of CTCs and PBCs before and after CCRT revealed that the clearance of CTC clusters and platelet counts at C1 might be potential biomarkers for predicting survival.

Gastric adenomas can be successfully treated with endoscopic resection, including endoscopic submucosal dissection (ESD) and endoscopic mucosal resection (EMR). The aim of this study was to evaluate and compare the efficacy of ESD and EMR with circumferential precutting (EMR-P) in the treatment of small gastric adenomas. This study included 1014 gastric adenomas ≤ 15 mm in diameter treated with ESD or EMR-P from 2012 to 2019, retrospectively. Propensity score matching between the ESD and EMR-P groups (1:1 to 3:1) was performed according to age, sex, tumor size, tumor location (upper, middle, and lower thirds), morphology, and preprocedural histology. The procedure time and the rates of en bloc resection, complete resection, adverse events, and local recurrence were compared between the two groups. After propensity score matching, 478 lesions (ESD: 295, EMR-P: 183) were analyzed. The rates of en bloc resection (94.9% vs. 93.4%, p = 0.498), complete resection (93.6% vs. 90.2%, p = 0.177), bleeding (8.1% vs. 3.8%, p = 0.063), and local recurrence (0.0% vs. 1.4%, p = 0.185) did not significantly differ between the two groups. The procedure time was significantly longer for ESD than for EMR-P (p

Background: The tendency toward conservative treatment for clavicle fractures in polytrauma patients may be related to certain characteristics of polytrauma patients. The purpose of this study was to analyze the factors that could affect delayed displacement of fractures during conservative treatment for clavicle fracture in polytrauma patients. Methods: From January 2013 to April 2017, 178 polytrauma patients with an ISS of 16 or more and a clavicle fracture were enrolled from a single trauma center. Of these patients, 79 who had an initial displacement of fractures of less than 100% of the clavicle diameter and initially underwent conservative treatment were included. We analyzed the risk factors that could affect delayed displacement of clavicle fracture by performing a regression analysis of the following factors: patients’ demographic characteristics, location of fracture, presence of comminuted fracture, duration of the intensive care unit stay, ventilator care, initial consciousness level, combined upper extremity injuries, rib fractures of the ipsilateral side, brain injury, and spinal cord injury.Results: A total of 31 patients had delayed displacement of clavicle fracture. The univariable and multivariable logistic regression analyses showed that the statistically significant risk factors for delayed displacement of clavicle fractures were the presence of comminuted fracture and middle third shaft clavicle fracture. Other factors were not statistically related to delayed displacement.Conclusion: Polytrauma patients with clavicle fractures are more likely to develop delayed displacement if there is a presence of comminuted fracture or middle third clavicle fracture. However, polytrauma-related factors did not reduce the risk of delayed displacement of clavicle fractures in polytrauma patients. Level of Evidence: III, retrospective cohort study

We report the ultrasonographic and MRI findings of an infected sclerosing lipogranuloma after scrotal hernioplasty. Sclerosing lipogranuloma is a rare foreign-body reaction of fat tissue, with most cases being associated with the genital and urinary tracts. To the best of our knowledge, MRI findings in sclerosing lipogranuloma in the scrotal sac have not yet been published and this is possibly the first study to report the case of an infected sclerosing lipogranuloma in the English literature.

Background The extraesophageal manifestations of gastroesophageal reflux disease (GERD) are more difficult to manage than the typical symptoms. The efficacy of high-dose and standard-dose proton pump inhibitors against these atypical symptoms is not yet established. Methods In this single center, randomized, open-label study, patients with GERD received rabeprazole for 8 weeks, either 20 mg once daily (standard-dose group) or 20 mg twice daily (high-dose group). Patients were assessed before treatment and at weeks 4 and 8 with a 5-graded scale questionnaire consisting of 2 typical symptoms (heartburn and acid regurgitation) and 8 atypical symptoms (chest pain, cough, globus, wheezing, laryngopharyngitis, hoarseness, belching, and dysphagia). Sufficient improvement of reflux symptoms was defined as ≥50% reduction from the initial questionnaire score. Results Final analyses included 35 patients in the standard-dose group and 38 patients in the high-dose group. The rate of sufficient improvement for typical symptoms was significantly higher in the high-dose group than in the standard-dose group (100.0% vs. 84.0%, P = 0.040). For atypical symptoms, the rate of sufficient improvement tended to be higher in the high-dose group than in the standard-dose group (82.4% vs. 63.0%, P = 0.087). Scores of typical and some atypical symptoms (cough and globus) improved after treatment, with significant inter-group differences in time-course changes. Conclusions High-dose rabeprazole is more effective for relieving typical GERD symptoms and some atypical symptoms such as cough and globus than a standard-dose regimen. Trial registration This research was enrolled in a registry of clinical trials run by United States National Library of Medicine at the National Institutes of Health (ClinicalTrials.gov Protocol Registration and Results system ID: NCT04001400). This study was registered on June 26, 2019 - Retrospectively registered.

Ureterosciatic hernia is extremely rare. In ureteral herniation, ureter prolapses occur through either the greater or lesser sciatic foramen. Atrophy of the piriformis muscle, hip joint diseases, and defects in the parietal pelvic fascia are predisposing factors for the development of ureterosciatic hernia. Most symptomatic patients have been treated surgically, with conservative treatment reserved only for asymptomatic patients. To the best of our knowledge, long-term follow-up outcomes after ureterosciatic hernia management are sparse. In this paper, we report the case of a 68-year-old woman who presented with colicky left abdominal pain. After computed tomography (CT) scan and anterograde pyelography, she was diagnosed ureterosciatic hernia with obstructive uropathy. We performed ureteral balloon dilatation and double-J ureteral stent placement. After this minimally invasive procedure, CT scan demonstrated that the left ureter had returned to its normal anatomical position without looping into the sciatic foramen. The patient remained asymptomatic with no adverse events 7 years after the minimally invasive procedures. This brief report describes ureterosciatic hernia successfully managed with minimally invasive procedures with long-term follow-up outcomes.

Purpose This study aimed to (1) quantitatively analyze the fibular footprints of the lateral collateral ligament (LCL) and popliteofibular ligament (PFL) and (2) evaluate whether a fibular tunnel can restore the LCL and PFL fibular footprints simultaneously without modification in anatomic posterolateral corner reconstruction of the knee. Methods In 20 cadaveric knees, anatomic characteristics, such as diameter, location and relationship with anatomic landmarks, of the LCL and PFL footprints were analyzed. Subsequently, a fibular tunnel that connected the LCL and PFL footprint centers was created with 1.5 mm drill bit, and tunnel depth, which is defined as the distance between the tunnel and the nearest cortex, was evaluated. An additional tunnel from the anteroinferior border of the LCL footprint to the posteroinferior border of the PFL footprint was created, and its tunnel depth was evaluated as well and compared with that of the original tunnel. Results The LCL footprint was longitudinally ovoid (8.4 ± 1.0 × 13 ± 1.0 mm), and its inferior margin corresponded well with the lateral apex of the fibula (distance, 1.0 ± 0.7 mm). The PFL footprint was round (9.7 ± 1.3 × 9.0 ± 1.1 mm), and its center was very close to the tip of the fibular styloid process (1.2 ± 0.8 mm). The tunnel depth of the original fibular tunnel was 1.8 ± 0.7 mm, and it was very shallow for tunnel reaming. On the contrary, the tunnel depth of the modified fibular tunnel (6.4 ± 1.1 mm) was significantly higher than that of the original tunnel (P Conclusions A single fibular tunnel cannot reproduce the LCL and PFL footprint centers simultaneously because the trajectory is too close to the cortex. A modified fibular tunnel, using the margins of the footprints, is recommended to avoid cortical blowout. Clinical Relevance A modified fibular tunnel that covers only portions of the LCL and PFL footprints, from the anteroinferior LCL footprint to the posteroinferior PFL footprint, is less likely to blow out the lateral fibula than is a similar tunnel using the anatomic footprint centers.

Background Ankle sprains are one of the most common musculoskeletal injuries. To guide management decisions, a clear insight into the relevant subgroups of patients with a potentially better or worse prognosis is important. This study aimed to evaluate injury severity, using ultrasonography (US), as a prognostic factor of acute ankle sprain and other possible factors including age, sex, body mass index (BMI), level of job activity, and level of sports activity. Materials and methods We retrospectively reviewed 28 patients with acute ankle sprain who reported at initial examination with an acutely twisted ankle. All patients had received a standard physical examination, radiography and standard ultrasound, to diagnose specific ligament injuries and their ankle sprain had been treated using standard conservative management. Various data including age, sex, BMI, level of sports activity, level of daily job activity, and final functional score (Foot and Ankle Outcome Scores, FAOS) were obtained. Mean comparison and correlations were used to assess risk factors. Risk factors associated with functional outcomes were evaluated using a multiple linear regression test. Results At final follow-up as 1 year after injury, FAOS differed significantly for injury severity, age, and BMI. There were no significant differences in sex, job activity, and exercise levels. The factor most affecting FAOS for both pain (FAOS-Pain) and symptoms (FAOS-Sx) was the number of completely torn ligaments. Age was the most important factor affecting the FAOS-Daily Living Activity (ADL). BMI was the most important factor for sports activity level (FAOS-Sports). Age and the number of completely torn ligaments were both important to FAOS-Sports and quality of life (FAOS-QOL). Conclusion The severity of injury, defined using US, was a prognostic factor for long-term outcome following acute ankle sprain. Therefore, US imaging of acute ankle ligament injury may be important to predict prognosis of acute ankle sprain.

The purpose of this study was to evaluate cartilage quality after internal fixation of osteochondral lesion of the talus (OLT) using second-look arthroscopies and MRIs. Thirty-four patients underwent internal fixation of OLTs involving large bone fragments. Twenty-one of these patients underwent second-look arthroscopies and 23 patients underwent MRIs postoperatively. The arthroscopic findings were assessed using the International Cartilage Repair Society (ICRS) grading system, and the MRI findings were evaluated using the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score. Five of the patients who underwent second-look arthroscopies showed normal cartilage, 12 showed nearly normal cartilage, 3 showed abnormal cartilage, and 1 showed severely abnormal cartilage, according to the overall ICRS repair grades. All the patients who achieved bone fragment union showed normal, or nearly normal cartilage upon second-look arthroscopy. The ICRS and MOCART scores were significantly higher for the patients with bone fragment union compared to those with nonunion (ICRS scores: 10.3 ± 1.5 vs. 6.0 ± 2.0, p p p = 0.55), and the signal intensities increased postoperatively to levels similar to the underlying talus when bone union was achieved. Second-look arthroscopy and MRI showed normal, or nearly normal, cartilage after internal fixation of OLTs when bone union was achieved. The nonunion of bone fragments resulted in inferior cartilage quality.

Background Upper tract urothelial carcinoma (UTUC) is rare and the treatment for recurrent or metastatic UTUC is unclear. We evaluated the outcomes of salvage and palliative radiotherapy (RT) and prognostic factors in UTUC patients and find implications for salvage and palliative RT. Methods Between August 2006 and February 2021, 174 patients (median age, 68 years; range, 37–90) underwent salvage and palliative RT. Disease status at RT included initially diagnosed advanced disease (n = 8, 4.6%), local recurrence only (n = 56, 32.2%), distant metastasis only (n = 59, 33.9%), and local recurrence and distant metastasis (n = 51, 29.3%). The primary tumor location included the renal pelvis (n = 87, 50%), ureter (n = 77, 44.3%), and both (n = 10, 5.7%). Radical nephroureterectomy, chemotherapy, and immunotherapy were used in 135 (77.6%), 101 (58%), and 19 (10.9%) patients, respectively. Survival outcomes and prognostic factors were analysed using Cox and logistic regression analysis. Results Salvage RT and palliative RT was administered in 73 (42%) and 101 (58%) patients, respectively. The median radiation dose was 45 Gy (range, 15–65). Two-dimensional (2D) or three-dimensional (3D) RT and intensity modulated RT (IMRT) were used in 61 (35.1%) and 113 (64.9%) patients, respectively. The median follow-up was 7.8 months. The median duration of overall survival (OS) was 13.4 months, and the 1-year OS was 53.5%. The median progression-free survival (PFS) was 4.7 months, and the 6-month PFS was 41.9%. The 6-month infield PFS was 84%. In multivariate analysis, RT method (2D/3D vs. IMRT, p = 0.007) and RT response (p = 0.008) were independent prognostic factors for OS, and RT response correlated with PFS (p = 0.015). In subgroup analysis in patients with PD-L1 data, positive PD-L1 correlated with better PFS (p = 0.009). RT response-associated factors were concurrent chemotherapy (p = 0.03) and higher radiation dose (p = 0.034). Of 145 patients, 10 (6.9%) developed grade 3 acute or late toxicity. Conclusions Salvage and palliative RT for UTUC are feasible and effective. Patients with RT response using IMRT may have survival benefit from salvage and palliative RT. Positive PD-L1 status might be related to radiosensitivity. High-dose radiation with concurrent chemotherapy may improve RT response.

Hospitalists are becoming increasingly involved in end-of-life (EOL) care decision making. They participate in the completion of physician orders for life-sustaining treatment (POLST) for patients who have not yet decided whether to proceed with life-sustaining treatment (LST) at the EOL. However, hospitalists are not physicians who have continuously treated patients in outpatient settings; hence, the continuity of care may be poor. We aimed to analyze the effect of outpatient physician involvement on the POLST completed by hospitalists.A retrospective cohort study was conducted in patients aged 18 years or older treated by hospitalists who completed POLST at Seoul National University Bundang Hospital from February 2018 to March 2020. The clinical and sociodemographic data were obtained through a medical chart review, and the differences in the characteristics of POLST were analyzed depending on the status of outpatient physician involvement.A total of 3,533 POLST forms were written, of which 175 (5.22%) were completed by the hospitalists. The proportion of POLSTs completed by hospitalists gradually increased from 2.53% in 2018 to 4.58% in 2019 and 15.9% in 2020. A total of 144 (82.3%) patients had malignancies, while 31 (17.7%) patients had non-cancer illnesses. In 47.4% of the patients, outpatient physicians were involved in completing physician's orders for LST. When the outpatient physicians were involved, more patients signed the POLST form themselves (P=0.02) and chose comfort measures only when asked to determine their preferred LST type (P=0.00).The completion of POLST by hospitalists is gradually increasing. LST was reduced when the outpatient physicians participated in the completion of POLST. Using measures to increase the involvement of outpatient providers in goal care discussions, the quality and goal concordance of EOL care can be improved.

The strength of the T cell receptor interaction with self-ligands affects antigen-specific immune responses. However, the precise function and underlying mechanisms are unclear. Here, we demonstrate that naive CD8+T cells with relatively high self-reactivity are phenotypically heterogeneous owing to varied responses to type I interferon, resulting in three distinct subsets, CD5loLy6C–, CD5hiLy6C–, and CD5hiLy6C+cells. CD5hiLy6C+cells differ from CD5loLy6C–and CD5hiLy6C–cells in terms of gene expression profiles and functional properties. Moreover, CD5hiLy6C+cells demonstrate more extensive antigen-specific expansion upon viral infection, with enhanced differentiation into terminal effector cells and reduced memory cell generation. Such features of CD5hiLy6C+cells are imprinted in a steady-state and type I interferon dependence is observed even for monoclonal CD8+T cell populations. These findings demonstrate that self-reactivity controls the functional diversity of naive CD8+T cells by co-opting tonic type I interferon signaling.

The gastrointestinal tract is the first organ directly affected by fasting. However, little is known about how fasting influences the intestinal immune system. Intestinal dendritic cells (DCs) capture antigens, migrate to secondary lymphoid organs, and provoke adaptive immune responses. We evaluated the changes of intestinal DCs in mice with short-term fasting and their effects on protective immunity against

STAT1 serves as a gatekeeper for naïve CD8 + T cell homeostasis by restraining type I IFN-STAT4-mTOR signaling axis.

The relationship between overall obesity, as measured by body mass index (BMI) and risk of esophageal squamous cell carcinoma (ESCC) has been reported to show a negative correlation. However, the relationship of ESCC, which accounts for around 90% of esophageal cancers in South Korea, with abdominal obesity, as measured by waist circumference (WC), may be different. Thus, we investigated the association between abdominal obesity and esophageal cancer in a nationwide population-based cohort. A retrospective cohort study of 22,809,722 individuals who had undergone regular health check-ups provided by the National Health Insurance Corporation between 2009 and 2012 (median follow-up period, 6.4 years) in South Korea was conducted. Abdominal obesity was defined as a WC > 90 cm for men and > 85 cm for women. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) using χ2 test and Cox proportional hazards model adjusted for confounding factors. The primary outcome was newly developed esophageal cancer. After adjusting for BMI, abdominal obesity increased the risk of esophageal cancer (HR 1.29, 95% CI 1.23–1.36). WC increased the risk for esophageal cancer in a dose-dependent manner (p values for trend

Background:Although an appropriate hinge position to prevent unstable lateral hinge fractures is well established in medial opening wedge high tibial osteotomy, the position during medial closing wedge distal femoral osteotomy has not been elucidated.Purpose/Hypothesis:The purpose was to evaluate the ideal hinge position that would prevent an unstable lateral hinge fracture during biplanar medial closing wedge distal femoral osteotomy based on soft tissue coverage and bone density around the hinge area. The hypothesis was that the ideal hinge position could be clarified by analyzing soft tissue coverage and bone density around the lateral hinge area.Study Design:Controlled laboratory study.Methods:In 20 cadaveric knees (mean age, 70.3 ± 19.2 years), the femoral attachment of the gastrocnemius lateral head was quantitatively analyzed as a soft tissue stabilizer using digital photography and fluoroscopy. Then, medial closing wedge distal femoral osteotomy was performed, locating the lateral hinge either inside (group 1) or outside (group 2) the femoral attachment of the gastrocnemius lateral head, and the incidence of unstable lateral hinge fractures was compared between the 2 groups. Cortical bone density around the lateral hinge was measured using Hounsfield units on 30 computed tomography scans and reconstructed as a 3-dimensional mapping model. The transitional zone with low bone density was regarded as the safe hinge position with an increased capacity for bone deformation.Results:The upper and lower margins of the femoral attachment of the gastrocnemius lateral head were 9.1 ± 0.9 mm above and 8.0 ± 1.4 mm below the upper border of the lateral femoral condyle, respectively, and the femoral attachment of the gastrocnemius lateral head was widest in the anteroposterior dimension 0.4 ± 1.7 mm above the upper border of the lateral femoral condyle. The incidence of unstable lateral hinge fractures during osteotomy was significantly decreased in group 1 compared with group 2 (group 1: 0/10; group 2: 5/10; P = .01). An isolated transitional zone with low bone density was observed in all 30 knees and located 1.3 ± 0.8 mm above the upper border of the lateral femoral condyle. Bone density of the transitional zone with low bone density was significantly lower than surrounding femoral cortices ( P < .001).Conclusion:Only the upper border of the lateral femoral condyle can be recommended as an ideal hinge position to prevent unstable lateral hinge fractures during biplanar medial closing wedge distal femoral osteotomy based on soft tissue coverage and bone density.Clinical Relevance:When the hinge is positioned at the upper border of the lateral femoral condyle during biplanar medial closing wedge distal femoral osteotomy, the risk of unstable hinge fractures can be minimized.

The purpose of the present study was to compare the outcomes of patients with Achilles tendon rupture treated with minimally invasive repair and early functional rehabilitation with the outcomes of similar patients treated with cast immobilization. After undergoing minimally invasive surgery, a below-knee splint with the foot in 30° of plantarflexion was applied to each patient for the first week. Patients were then assigned to a cast immobilization group (IG; n = 25) or a functional group (FG; n = 16). Data were collected during outpatient checks at 6 weeks, 3 months, 6 months, and 1 year. Outcomes of interest included range of motion (ROM), heel height, calf circumference, pain and functional score, return to work and light sports activity, and complications. The time interval for return to work in the FG was faster than that in the IG (p = .026). There was no clinically important difference between the 2 groups with regard to heel height, ROM, return to sports, calf circumference, visual analog scale, American Orthopaedic Foot and Ankle Society score, or Achilles tendon Total Rupture Score at every outpatient check except ROM difference at 6 weeks and heel height at 3 months. Rerupture occurred in 2 patients (1 [4%] in the IG and 1 [6.25%] in the FG). Early functional rehabilitation seemed to be as safe as traditional postoperative immobilization with a similar functional result and complications, but it was advantageous for the early phase of rehabilitation only.

Cyclic dinucleotides (CDNs), such as cyclic diadenylate monophosphate and cyclic diguanylate monophosphate, are commensal bacteria-derived second messengers in the gut that modulate bacterial survival, colonization, and biofilm formation. Recently, CDNs have been discovered to have an immunomodulatory activity by inducing the expression of type I interferon (IFN) through STING signaling pathway in macrophages. Because CDNs are possibly absorbed and delivered into the bone marrow, where bone-resorbing osteoclasts are derived from monocyte/macrophage lineages, CDNs could affect bone metabolism by regulating osteoclast differentiation. In this study, we investigated the effect of CDNs on the differentiation and function of osteoclasts and osteoblasts. When bone marrow-derived macrophages (BMMs) were differentiated into osteoclasts with macrophage colony-stimulating factor (M-CSF) and receptor activator of NF-κB ligand (RANKL) in the presence of CDNs, the differentiation was inhibited by CDNs in a dose-dependent manner. In contrast, CDNs did not influence the differentiation of committed osteoclasts or osteoblast precursors. STING signaling pathway appeared to be critical for CDNs-mediated inhibition of osteoclast differentiation since CDNs induced the phosphorylation of TBK1 and IRF3, a representative feature of STING activation, and osteoclast differentiation was restored in STING knockdown BMMs with siRNA. Moreover, CDNs increased the mRNA expression of STING-meditated IFN-β, which is a negative regulator of osteoclastogenesis. In addition, CDNs also induced the phosphorylation of STAT1, which mediates IFN-α/β receptor (IFNAR) signal transduction. The inhibitory effects of CDNs on osteoclast differentiation were not observed in the presence of antibody blocking IFNAR or in macrophages derived from IFNAR1-/- mice. Experiments using a mouse calvarial implantation model showed that RANKL-induced bone resorption was inhibited by CDNs. Taken together, these results suggest that CDNs inhibit osteoclast differentiation and bone resorption through induction of IFN-β via the STING signaling pathway. © 2019 American Society for Bone and Mineral Research.

Skeletal dysplasia (SD), a heterogeneous disease group with rare incidence and various clinical manifestations, is associated with multiple causative genes. For clinicians, accurate diagnosis of SD is clinically and genetically difficult. The development of next-generation sequencing (NGS) has substantially aided in the genetic diagnosis of SD. In this study, we conducted a targeted NGS of 437 genes – included in the nosology of SD published in 2019 – in 31 patients with a suspected SD. The clinical and genetic diagnoses were confirmed in 16 out of the 31 patients, and the diagnostic yield was 51.9%. In these patients, 18 pathogenic variants were found in 13 genes (COL2A1, MYH3, COMP, MATN3, CTSK, EBP, CLCN7, COL1A2, EXT1, TGFBR1, SMAD3, FIG4, and ARID1B), of which, four were novel variants. The diagnosis rate was very high in patients with a suspected familial SD and with radiological evidence indicating clinical SD (11 out of 15, 73.3%). In patients with skeletal involvement and other clinical manifestations including dysmorphism or multiple congenital anomalies, and various degrees of developmental delay/intellectual disability, the diagnosis rate was low (5 out of 16, 31.2%) but rare syndromic SD could be diagnosed. In conclusion, NGS-based gene panel sequencing can be helpful in diagnosing SD which has clinical and genetic heterogeneity. To increase the diagnostic yield of suspected SD patients, it is important to categorize patients based on the clinical features, family history, and radiographic evidence.