Predictors associated with the rate of progression of nigrostriatal degeneration in Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) manifests as a wide variety of clinical phenotypes and its progression varies greatly. However, the factors associated with different disease progression remain largely unknown. METHODS: In this retrospective cohort study, we enrolled 113 patients who underwent 18F-FP-CIT PET scan twice. Given the negative exponential progression pattern of dopamine loss in PD, we applied the natural logarithm to the specific binding ratio (SBR) of two consecutive 18F-FP-CIT PET scans and conducted linear mixed model to calculate individual slope to define the progression rate of nigrostriatal degeneration. We investigated the clinical and dopamine transporter (DAT) availability patterns associated with the progression rate of dopamine depletion in each striatal sub-region. RESULTS: More symmetric parkinsonism, the presence of dyslipidemia, lower K-MMSE total score, and lower anteroposterior gradient of the mean putaminal SBR were associated with faster progression rate of dopamine depletion in the caudate nucleus. More symmetric parkinsonism and lower anteroposterior gradient of the mean putaminal SBR were associated with faster depletion of dopamine in the anterior putamen. Older age at onset, more symmetric parkinsonism, the presence of dyslipidemia, and lower anteroposterior gradient of the mean putaminal SBR were associated with faster progression rate of dopamine depletion in the posterior putamen. Lower striatal mean SBR predicted the development of LID, while lower mean SBR in the caudate nuclei predicted the development of dementia. DISCUSSION: Our results suggest that the evaluation of baseline clinical features and patterns of DAT availability can predict the progression of PD and its prognosis.

Anterolateral Dual Plate Fixation for Distal Metaphyseal-Diaphyseal Junction Fractures of the Humerus: Biomechanical Finite Element Analysis with Clinical Results.

Background: Distal metaphyseal-diaphyseal junction fractures of the humerus are a subset of injuries between humeral shaft fractures and distal intra-articular humerus fractures. A lack of space for distal fixation and the unique anatomy of concave curvature create difficulties during operative treatment. The closely lying radial nerve is another major concern. The aim of this study was to determine whether anterolateral dual plate fixation could be effective for a distal junctional fracture of the humerus both biomechanically and clinically. Methods: A right humerus 3-dimensional (3D) model was obtained based on plain radiographs and computed tomography data of patients. Two fractures, a spiral type and a spiral wedge type, were constructed. Three-dimensional models of locking compression plates and screws were constructed using materials provided by the manufacturer. The experiment was conducted by using COMSOL Multiphysics, a finite element analysis, solver, and simulation software package. For the clinical study, from July 2008 to March 2021, a total of 72 patients were included. Their medical records were retrospectively reviewed to obtain patient demographics, elbow range of motion, Disabilities of the Arm, Shoulder and Hand (DASH) scores, Mayo Elbow Performance Scores (MEPS), and hand grip strength. Results: No fracture fixation construct completely restored stiffness comparable to the intact model in torsion or compression. Combinations of the 7-hole and 5-hole plates and the 8-hole and 6-hole plates showed superior structural stiffness and stress than those with single lateral plates. At least 3 screws (6 cortices) should be inserted into the lateral plate to reduce the load effectively. For the anterior plate, it was sufficient to purchase only the near cortex. Regarding clinical results of the surgery, the range of motion showed satisfactory results in elbow flexion, elbow extension, and forearm rotation. The average DASH score was 4.3 and the average MEPS was 88.2. Conclusions: Anterolateral dual plate fixation was biomechanically superior to the single-plate method in the finite element analysis of a distal junctional fracture of the humerus model. Anterolateral dual plate fixation was also clinically effective in a large cohort of patients with distal junctional fractures of the humerus.

Design, Synthesis, and Biological Evaluation of New 2,6,7-Substituted Purine Derivatives as Toll-like Receptor 7 Agonists for Intranasal Vaccine Adjuvants.

TLR7/8 agonists are versatile immune stimulators capable of treating various diseases such as viral infections, autoimmune, and cancer. Despite the structural similarity of TLR7/8, their immune stimulation mechanisms and time-course responses significantly differ. In this study, a new series of TLR7-selective agonists was synthesized utilizing the economical building block 2,6-dichloropurine. Compound 27b showed the most potent activity on hTLR7 with an EC50 of 17.53 nM and demonstrated high hTLR7 selectivity (224 folds against TLR8). 27b effectively stimulated the secretion of proinflammatory cytokines in mouse macrophages and enhanced intranasal vaccine efficacy against influenza A virus in vivo. Assessment of humoral and mucosal antibody titers confirmed that 27b elevates IgG and IgA levels, protecting against both homologous and heterologous influenza viral infections. These findings suggest that 27b is a promising candidate as a vaccine adjuvant to prevent viral infections or as a robust immunomodulator with prolonged activity for treating immune-suppressed diseases.

Inhibition of endocytic uptake of severe acute respiratory syndrome coronavirus 2 and endo-lysosomal acidification by diphenoxylate.

Cell culture-based screening of a chemical library identified diphenoxylate as an antiviral agent against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The observed 50% effective concentrations ranged between 1.4 and 4.9 µM against the original wild-type strain and its variants. Time-of-addition experiments indicated that diphenoxylate is an entry blocker targeting a host factor involved in viral infection. Fluorescence microscopic analysis visualized that diphenoxylate prevented SARS-CoV-2 particles from penetrating the cell membrane and also impaired endo-lysosomal acidification. Diphenoxylate exhibited a synergistic inhibitory effect on SARS-CoV-2 infection in human lung epithelial Calu-3 cells when combined with a transmembrane serine protease 2 (TMPRSS2) inhibitor, nafamostat. This synergy suggested that efficient antiviral activity is achieved by blocking both TMPRSS2-mediated early and endosome-mediated late SARS-CoV-2 entry pathways. The antiviral efficacy of diphenoxylate against SARS-CoV-2 was reproducible in a human tonsil organoids system. In a transgenic mouse model expressing the obligate SARS-CoV-2 receptor, human angiotensin-converting enzyme 2, intranasal administration of diphenoxylate (10 mg/kg/day) significantly reduced the viral RNA copy number in the lungs by 70% on day 3. This study underscores that diphenoxylate represents a promising core scaffold, warranting further exploration for chemical modifications aimed at developing a new class of clinically effective antiviral drugs against SARS-CoV-2.

Association of Basal Forebrain Volume with Amyloid, Tau, and Cognition in Alzheimer's Disease.

Background: Degeneration of cholinergic basal forebrain (BF) neurons characterizes Alzheimer's disease (AD). However, what role the BF plays in the dynamics of AD pathophysiology has not been investigated precisely. Objective: To investigate the baseline and longitudinal roles of BF along with core neuropathologies in AD. Methods: In this retrospective cohort study, we enrolled 113 subjects (38 amyloid [Aß]-negative cognitively unimpaired, 6 Aß-positive cognitively unimpaired, 39 with prodromal AD, and 30 with AD dementia) who performed brain MRI for BF volume and cortical thickness, 18F-florbetaben PET for Aß, 18F-flortaucipir PET for tau, and detailed cognitive testing longitudinally. We investigated the baseline and longitudinal association of BF volume with Aß and tau standardized uptake value ratio and cognition. Results: Cross-sectionally, lower BF volume was not independently associated with higher cortical Aß, but it was associated with tau burden. Tau burden in the orbitofrontal, insular, lateral temporal, inferior temporo-occipital, and anterior cingulate cortices were associated with progressive BF atrophy. Lower BF volume was associated with faster Aß accumulation, mainly in the prefrontal, anterior temporal, cingulate, and medial occipital cortices. BF volume was associated with progressive decline in language and memory functions regardless of baseline Aß and tau burden. Conclusions: Tau deposition affected progressive BF atrophy, which in turn accelerated amyloid deposition, leading to a vicious cycle. Also, lower baseline BF volume independently predicted deterioration in cognitive function.

CO2-Free Ethylene Oxide Production via Liquid-Phase Epoxidation with Fe2O3/MSM Catalyst.

In this study, we present an approach for ethylene oxide (EO) production that addresses environmental concerns by eliminating greenhouse gas emissions. Our catalyst, Fe2O3/MSM, was synthesized using a hydrothermal method, incorporating Fe2O3 nanoparticles into a well-structured mesoporous silica matrix (MSM). We selected peracetic acid as the oxidant, enabling CO2-free EO production while yielding valuable by-products such as acetic acid, monoethylene glycol, and diethylene glycol. X-ray diffraction (XRD), X- ray photoelectron spectroscopy (XPS), and Brunauer-Emmett-Teller (BET) analyses confirmed the heteroatom structure of the catalysts and porosity, while Transmission electron microscopy (TEM) analysis provided insights into its morphology. Then, the synthesized catalyst was used in the liquid-phase epoxidation of ethylene for EO production. Our systematic experiments involved varying critical parameters such as temperature, ethylene to oxidant ratio, catalyst dosage, and solvent to optimize EO selectivity and ethylene conversion. The results of this study demonstrated an 80.2 % ethylene conversion to EO with an EO selectivity of 87.6 %. The production process yielded valuable by-products without CO2 emissions, highlighting its environmental friendliness.

Clinical characteristics and outcome of lung cancer in patients with fibrosing interstitial lung disease.

BACKGROUND: Lung cancer (LC) is an important comorbidity of interstitial lung disease (ILD) and has a poor prognosis. The clinical characteristics and outcome of each ILD subtype in LC patients have not been sufficiently investigated. Therefore, this study aimed to evaluate the difference between idiopathic pulmonary fibrosis (IPF) and non-IPF ILD as well as prognostic factors in patients with ILD-LC. METHODS: The medical records of 163 patients diagnosed with ILD-LC at Asan Medical Center from January 2018 to May 2023 were retrospectively reviewed. Baseline characteristics and clinical outcomes were compared between the IPF-LC and non-IPF ILD-LC groups, and prognostic factors were analyzed using the Cox proportional-hazard model. RESULTS: The median follow-up period was 11 months after the cancer diagnosis. No statistically significant differences were observed in clinical characteristics and mortality rates (median survival: 26 vs. 20 months, p = 0.530) between the groups. The independent prognostic factors in patients with ILD-LC were higher level of Krebs von den Lungen-6 (≥ 1000 U/mL, hazard ratio [HR] 1.970, 95% confidence interval [CI] 1.026-3.783, p = 0.025) and advanced clinical stage of LC (compared with stage I, HR 3.876 for stage II, p = 0.025, HR 5.092 for stage III, p = 0.002, and HR 5.626 for stage IV, p = 0.002). In terms of treatment, surgery was the significant factor for survival (HR 0.235; 95% CI 0.106-0.520; p < 0.001). CONCLUSIONS: No survival difference was observed between IPF-LC and non-IPF ILD-LC patients. A higher level of Krebs von den Lungen-6 may act as a prognostic marker in ILD-LC patients.

Comparison of resumption of ovulation after cessation of oral contraceptives and medroxyprogesterone acetate in women with polycystic ovary syndrome.

OBJECTIVE: Both oral contraceptive pills (OCPs) and cyclic medroxyprogesterone acetate (MPA) are widely used to control menstrual abnormalities in women with polycystic ovary syndrome (PCOS). We aimed to evaluate the chance of ovulation resumption after cessation of OCPs and MPA in women with PCOS. METHODS: A retrospective study was conducted of women with PCOS who were treated with OCPs or cyclic MPA from September 2015 to March 2019. After cessation of medication, ovulation was assessed using basal body temperature and/or measurement of serum progesterone. The odds ratio for ovulation resumption was assessed with multivariable logistic regression. Additionally, doubly robust analysis was performed with inverse-probability-weighted analysis and regression adjustment based on the covariate balancing propensity score to adjust for the effect of covariates on the treatment assignment. RESULTS: Among 272 women with PCOS, 136 were prescribed OCPs and 136 were prescribed cyclic MPA. Ovulation resumed in 18.4% of women (n = 25) after cessation of MPA and in 24.3% of women (n = 33) after cessation of OCPs. The odds of ovulation resumption in MPA users were comparable with those in OCP users (adjusted odds ratio (aOR) 1.00, 95% confidence interval (CI) 0.89-1.12). After multiple imputation due to missing values, the results did not change substantially (aOR 0.99, 95% CI 0.89-1.10). CONCLUSIONS: Among women with PCOS, MPA users have a similar chance of ovulation resumption as OCP users after cessation of medication. Cyclic MPA can be a good alternative to OCPs in women for whom OCPs are contraindicated or who decline to take OCPs.

Direction-selective Resistance to Cerebrospinal Fluid Flow as the Cause of Syringomyelia.

The pathophysiology of syringomyelia remains poorly understood. Two prevailing challenges stand out: the need for a comprehensive understanding of its diverse types and the yet-to-be-explained mechanism of cerebrospinal fluid (CSF) retention in the syrinx despite its higher pressure than that in the adjacent subarachnoid space. Expanding on our previous proposal that direction-selective resistance to subarachnoid CSF flow drives syringomyelia genesis, this study uses a computer model to explore this mechanism further. We developed a computer simulation model to study spinal CSF dynamics, employing a lumped parameter approach with multiple compartments. This model replicated the to-and-fro movement of CSF in the spinal subarachnoid space and within an intraspinal channel. Subsequently, a direction-selective resistance-opposing only the caudal subarachnoid CSF flow-was introduced at a specific location within the subarachnoid space. Following the introduction of the direction-selective resistance, a consistent pressure increase was observed in the intraspinal channel downstream of the resistance. Importantly, this increase in pressure accumulated with every cycle of to-and-fro CSF flow. The accumulation results from the pressure drop across the resistance, and its effect on the spinal cord matrix creates a pumping action in the intraspinal channel. Our findings elucidate the mechanisms underlying our hypothesis that a direction-selective resistance to subarachnoid CSF flow causes syringomyelia. This comprehensively explains the various types of syringomyelia and resolves the puzzle of CSF retention in the syrinx despite a pressure gradient.

Different effect of hypo- and hypermetabolism on cognition in dementia with Lewy bodies: are they coupled or independent?

Patients with dementia with Lewy bodies (DLB) show widespread brain metabolic changes. This study investigated whether brain hypo- and hypermetabolism in DLB have differential effects on cognition. We enrolled 55 patients with DLB (15 prodromal DLB [MCI-LB] and 40 probable DLB) and 13 healthy controls who underwent 18F-fluorodeoxyglucose positron emission tomography and detailed neuropsychological tests. Metabolic indices reflecting associated changes in regional cerebral glucose metabolism were calculated as follows: index(-) for hypometabolism [DLB-hypo] and index(+) for hypermetabolism [DLB-hyper]. The effects of DLB-hypo or DLB-hyper on cognitive function were assessed using a multivariate linear regression model. Additionally, a linear mixed model was used to investigate the association between each index and the longitudinal cognitive decline. There was no correlation between DLB-hypo and DLB-hyper in the disease group. The multivariate linear regression model showed that DLB-hypo was associated with language, visuospatial, visual memory, and frontal/executive functions; whereas DLB-hyper was responsible for attention and verbal memory. There was significant interaction between DLB-hypo and DLB-hyper for verbal and visual memory, which was substantially affected by DLB-hyper in relatively preserved DLB-hypo status. A linear mixed model showed that DLB-hypo was associated with longitudinal cognitive outcomes, regardless of cognitive status, and DLB-hyper contributed to cognitive decline only in the MCI-LB group. The present study suggests that DLB-hypo and DLB-hyper may be independent of each other and differentially affect the baseline and longitudinal cognitive function in patients with DLB.

Clinical outcomes of extensor indicis proprius tendon transfer for extensor pollicis longus tendon rupture.

LEVEL OF EVIDENCE: IV.

Comparison of survival prediction models for bone metastases of the extremities following surgery.

Aims: This study aimed to compare the performance of survival prediction models for bone metastases of the extremities (BM-E) with pathological fractures in an Asian cohort, and investigate patient characteristics associated with survival. Methods: This retrospective cohort study included 469 patients, who underwent surgery for BM-E between January 2009 and March 2022 at a tertiary hospital in South Korea. Postoperative survival was calculated using the PATHFx3.0, SPRING13, OPTIModel, SORG, and IOR models. Model performance was assessed with area under the curve (AUC), calibration curve, Brier score, and decision curve analysis. Cox regression analyses were performed to evaluate the factors contributing to survival. Results: The SORG model demonstrated the highest discriminatory accuracy with AUC (0.80 (95% confidence interval (CI) 0.76 to 0.85)) at 12 months. In calibration analysis, the PATHfx3.0 and OPTIModel models underestimated survival, while the SPRING13 and IOR models overestimated survival. The SORG model exhibited excellent calibration with intercepts of 0.10 (95% CI -0.13 to 0.33) at 12 months. The SORG model also had lower Brier scores than the null score at three and 12 months, indicating good overall performance. Decision curve analysis showed that all five survival prediction models provided greater net benefit than the default strategy of operating on either all or no patients. Rapid growth cancer and low serum albumin levels were associated with three-, six-, and 12-month survival. Conclusion: State-of-art survival prediction models for BM-E (PATHFx3.0, SPRING13, OPTIModel, SORG, and IOR models) are useful clinical tools for orthopaedic surgeons in the decision-making process for the treatment in Asian patients, with SORG models offering the best predictive performance. Rapid growth cancer and serum albumin level are independent, statistically significant factors contributing to survival following surgery of BM-E. Further refinement of survival prediction models will bring about informed and patient-specific treatment of BM-E.

Differential effects of cholesterol levels on cognition according to body mass index in Parkinson's disease.

BACKGROUND: Cholesterol is an essential component of the neuronal cell membrane and is crucial for neuronal function; however, the role of cholesterol levels in Parkinson's disease (PD) is debatable. This study investigated the complex relationship between total cholesterol (TC) levels, body mass index (BMI), and cognition in patients with PD. METHODS: This study included 321 drug-naïve patients with PD who underwent dopamine transporter (DAT) imaging and baseline neuropsychological tests. Multivariate linear regression and Cox regression models were used to investigate the effect of TC levels on the composite score of each cognitive domain and dementia conversion after adjusting for covariates, respectively. Interaction analyses were performed to examine the interaction effect between TC levels and BMI on baseline cognition and dementia conversion. RESULTS: TC levels and cognition showed no significant relationship after adjusting for potential confounders. A significant interaction effect between TC levels and BMI was observed in frontal/executive function and dementia conversion. Further analyses showed that TC levels were positively associated with frontal/executive function in the under-/normal weight group (ß = 0.205, p = 0.013), whereas a negative relationship existed between TC levels and frontal/executive function in the obese group (ß = - 0.213, p = 0.017). Cox regression analyses also showed the differential effects of TC levels on dementia conversion according to BMI (under-/normal weight group: hazard ratio [HR] = 0.550, p = 0.013; obese group: HR = 2.085, p = 0.014). CONCLUSIONS: This study suggests a cross-over interaction between TC levels and BMI on cognitive symptoms in PD.

Recovery-focused self-help intervention using vodcasts for patients with personality disorder: feasibility randomised controlled trial.

BACKGROUND: Availability of long-term psychological interventions for personality disorders is limited because of their high intensity and cost. Research in evidence-based, low-intensity interventions is needed. AIMS: This study aimed to examine the feasibility, acceptability and potential impact of a low-intensity, digital guided self-help (GSH) intervention that is focused on emotion regulation, recovery-oriented and provides in-the-moment delivery for patients with personality disorders. METHOD: We conducted a single-blind feasibility trial. A total of 43 patients with a personality disorder were recruited and randomly assigned to either a GSH arm (n = 22) or a treatment-as-usual arm (n = 21). The GSH intervention included a series of short videos offering psychoeducation and support, personalised feedback using text messages, and supportive telephone calls, for 4 weeks in addition to treatment as usual. Outcomes of emotional disturbance, emotion dysregulation, self-harm behaviours and decentring ability were measured at baseline, 4 weeks (end of intervention) and 8 weeks (follow-up). RESULTS: All patients who attended the first session continued until the last session. There was an interaction effect between time and group on anxiety (P = 0.027, Δη2 = 0.10), where the GSH group showed a significant reduction in anxiety at follow-up (P = 0.003, d = 0.25). The GSH group increased in decentring ability at the end of intervention (P = 0.007, d = -0.65), and the decrease in self-harm behaviours continued until follow-up (P = 0.02, d = 0.57). CONCLUSIONS: The results suggest that a personalised digital GSH with a focus on recovery could reduce anxiety and self-harm behaviours at short-term follow-up.

Amputation in patients with extremity soft tissue sarcoma: the experience of an East Asian referral center.

BACKGROUND: This study aimed to investigate the characteristics and clinical outcomes in a series of patients with extremity soft tissue sarcoma (STS) who underwent amputation at a large East Asian referral center. PATIENTS AND METHODS: Of the 652 patients who underwent surgery for extremity STS, data of 37 consecutive patients who underwent amputation were reviewed retrospectively. The median follow-up period was 96.0 months (range, 15-216). The patients were classified in to three cohorts. The primary localized (PL) group included patients who underwent amputation as a primary surgical procedure with curative intent. The recurrent localized (RL) group included patients who underwent amputation as a revision procedure after failure of previous limb sparing surgeries. The metastatic group included patients who underwent amputation as a palliative procedure. RESULTS: There were 22 cases of amputation in 596 STS patients and the amputation rate was 3.6% (22/596). Further, 1.8% (9/490) of patients with primary localized STS underwent amputation. Patients with localized STS who underwent amputation had a 5-year disease-specific survival (DSS) rate of 89.9% (95% Confidence Interval (CI), 87.1-92.7%), a local-recurrence-free survival (LRFS) of 84.1% (95% CI, 80.5-87.6%), and a metastasis-free survival (MFS) of 84.6%. (95% CI, 81.1-88.0%) Compared with previous studies, our results showed higher DSS and MFS rates with similar LRFS. CONCLUSIONS: The amputation rate of extremity STS in our institute in East Asia was similar but slightly lower than that reported in Western studies. The oncologic outcome of amputation reported in this study was higher than that indicated in Western studies and oncologic outcome of amputation was not statistically different from those of limb salvage surgery. However, considering the small cohort in single institute study, there is a possibility of selection bias and future multi-center study is necessary. From our results, amputation is still a feasible option for appropriately selected patients unsuitable for limb-conserving surgery.

Profiles of perceived resources among low-income, rural mothers: Prospective associations with maternal and child outcomes.

Low-income, rural families face significant mental health risks. However, the understanding of resources associated with mental health risks is limited. The present study investigated the associations between perceived resources of low-income, rural mothers, and longitudinal maternal and child outcomes. This study utilized longitudinal data from the Family Life Project (N = 1203), from US rural areas with high poverty rates. Mothers reported their resources at 6-month postpartum, and their levels of depression, anxiety, and role overload were assessed at 2-year postpartum. Mothers reported their children's behavioral problems at 3 years old. Using a person-centered approach, we identified four maternal profiles: lower resources (7.1%); higher intra-family support (11.1%); higher inter-family support (20.8%); and higher resources (60.9%). In general, the higher resource profile was associated with lower mental health concerns of mothers and lower levels of behavior problems of children. Mothers in the higher intra-family support profile had disproportionately higher role overload. Children of mothers in the higher inter-family support profile showed disproportionately higher behavioral problems. Maternal partner status and education were significant predictors of resource profiles. Findings support the heterogeneity in perceived resources among low-income, rural families and different risk levels. Identifying these subgroups has significant implications for policy and interventions aimed toward this vulnerable population.

Infant sleep interventions with sleep measurements using actigraphy: A systematic review.

AIM: This review investigated the outcomes and methodological quality of infant sleep intervention studies utilizing actigraphy. BACKGROUND: Parents need appropriate support for infant sleep from nurses. There are few methodological reports of actigraphy in infant sleep intervention studies that objectively measure infant sleep in a natural setting. DESIGN: This was a systematic review study. DATA SOURCES: Ovid MEDLINE, Embase, Cochrane, CINAHL and PsycINFO were searched from database establishment to 30 December 2021. REVIEW METHODS: This systematic review utilized the Cochrane Collaboration review guidelines. RESULTS: Eleven sleep intervention studies were reviewed. Three used extinction-based behavioural interventions, and eight included parental education programs. The infant sleep interventions positively affected the sleep outcomes of both infants and parents. Fairly consistent effects were found on infants' number of awakenings and sleep onset latency. However, parental psychosocial outcomes were inconsistent. All studies reported device placement, the algorithm for analysis, the use of a sleep diary and number of days/nights, but external movements affecting infants' sleep records were insufficiently reported. Only two studies had a low risk of bias. CONCLUSIONS: The infant sleep interventions had positive effects on both infants and their parents. Comprehensive methodological considerations are required for more standardized assessments using actigraphy for infant sleep evaluation.

Case Series of Soft Tissue Sarcoma Patients with Brain Metastasis with Implications from Genomic and Transcriptomic Analysis.

PURPOSE: Brain metastasis rarely occurs in soft tissue sarcoma (STS). Here, we present five cases of STS with brain metastases with genetic profiles. MATERIALS AND METHODS: We included five patients from Seoul National University Hospital who were diagnosed with STS with metastasis to the brain. Tissue from the brain metastasis along with that from the primary site or other metastases were used for DNA and RNA sequencing to identify genetic profiles. Gene expression profiles were compared with sarcoma samples from The Cancer Genome Atlas. RESULTS: The overall survival after diagnosis of brain metastasis ranged from 2.2 to 34.3 months. Comparison of mutational profiles between brain metastases and matched primary or other metastatic samples showed similar profiles. In two patients, copy number variation profiles between brain metastasis and other tumors showed several differences including MYCL, JUN, MYC, and DDR2 amplification. Gene ontology analysis showed that the group of genes significantly highly expressed in the brain metastasis samples was enriched in the G-protein coupled receptor activity, structural constituent of chromatin, protein heterodimerization activity, and binding of DNA, RNA, and protein. Gene set enrichment analysis showed enrichment in the pathway of neuroactive ligand-receptor interaction and systemic lupus erythematosus. CONCLUSION: The five patients had variable ranges of clinical courses and outcomes. Genomic and transcriptomic analysis of STS with brain metastasis implicates possible involvement of complex expression modification and epigenetic changes rather than the addition of single driver gene alteration.

Surgical Treatment for Patients with Post-traumatic Flexion Contracture of Proximal Interphalangeal Joint: Analysis of Various Affecting Factors.

Background: A flexion contracture (FC) of the proximal interphalangeal (PIP) joint can have a profound negative influence on daily activity. The outcomes of surgical release of the PIP joint in literature are based on small sample size studies done several decades ago. The aim of this study is to report the outcomes of surgical treatment for post-traumatic FC of the PIP joint and to identify factors that affect these outcomes. Methods: This single institute retrospective study included patients from 2000 to 2020. We only included patients with post-traumatic FC of the PIP joint. We evaluated the demographic characteristics, cause of FC, surgical approaches and the various procedures conducted. We surveyed postoperative complications. During the study period, we asked about their current symptoms and evaluated their operative outcomes as excellent, good, fair or poor through the phone. Results: The average FC recovery angle was 37.3°. The small finger was the most affected, and the most common cause of FC was a tendon laceration. The volar plate complex release was the most frequently conducted procedure. The FC improvement was positively correlated to the degree of preoperative FC. The more severe preoperative flexion-extension arc was presented, the more FC recovery was achieved after operation. Patients who underwent multiple procedures had a higher degree of preoperative FC, and better correction was achieved with multiple procedures than with a single procedure. The most critical complication was recurrence. Conclusions: We were able to obtain average 37.3° of extension by surgical treatment. The more severe the FC presented before surgery, the greater the need for multiple procedures, however, this resulted in a significant increase in joint extension. Nevertheless, caution should be exercised regarding recurrence and could occur even with an experienced surgeon. Level of Evidence: Level IV (Therapeutic).