ℓ 1 -Regularized ICA: A Novel Method for Analysis of Task-Related fMRI Data.

We propose a new method of independent component analysis (ICA) in order to extract appropriate features from high-dimensional data. In general, matrix factorization methods including ICA have a problem regarding the interpretability of extracted features. For the improvement of interpretability, sparse constraint on a factorized matrix is helpful. With this background, we construct a new ICA method with sparsity. In our method, the ℓ1-regularized IC term is added to the cost function of ICA, and minimization of the cost function is performed by a difference of convex functions algorithm. For the validity of our proposed method, we apply it to synthetic data and real functional magnetic resonance imaging data.

Acute lung injury and post-cardiac arrest syndrome: a narrative review.

BACKGROUND: Post-cardiac arrest syndrome (PCAS) presents a multifaceted challenge in clinical practice, characterized by severe neurological injury and high mortality rates despite advancements in management strategies. One of the important critical aspects of PCAS is post-arrest lung injury (PALI), which significantly contributes to poor outcomes. PALI arises from a complex interplay of pathophysiological mechanisms, including trauma from chest compressions, pulmonary ischemia-reperfusion (IR) injury, aspiration, and systemic inflammation. Despite its clinical significance, the pathophysiology of PALI remains incompletely understood, necessitating further investigation to optimize therapeutic approaches. METHODS: This review comprehensively examines the existing literature to elucidate the epidemiology, pathophysiology, and therapeutic strategies for PALI. A comprehensive literature search was conducted to identify preclinical and clinical studies investigating PALI. Data from these studies were synthesized to provide a comprehensive overview of PALI and its management. RESULTS: Epidemiological studies have highlighted the substantial prevalence of PALI in post-cardiac arrest patients, with up to 50% of survivors experiencing acute lung injury. Diagnostic imaging modalities, including chest X-rays, computed tomography, and lung ultrasound, play a crucial role in identifying PALI and assessing its severity. Pathophysiologically, PALI encompasses a spectrum of factors, including chest compression-related trauma, pulmonary IR injury, aspiration, and systemic inflammation, which collectively contribute to lung dysfunction and poor outcomes. Therapeutically, lung-protective ventilation strategies, such as low tidal volume ventilation and optimization of positive end-expiratory pressure, have emerged as cornerstone approaches in the management of PALI. Additionally, therapeutic hypothermia and emerging therapies targeting mitochondrial dysfunction hold promise in mitigating PALI-related morbidity and mortality. CONCLUSION: PALI represents a significant clinical challenge in post-cardiac arrest care, necessitating prompt diagnosis and targeted interventions to improve outcomes. Mitochondrial-related therapies are among the novel therapeutic strategies for PALI. Further clinical research is warranted to optimize PALI management and enhance post-cardiac arrest care paradigms.

Temporal effects of lascufloxacin on human gut and salivary microbiota: Analysis using next-generation sequencing method.

INTRODUCTION: Antimicrobial treatment disrupts human microbiota. The effects of lascufloxacin (LSFX), a new fluoroquinolone, on human microbiota remains unknown. Therefore, in this study, we aimed to evaluate the effects of LSFX administration on the gut and salivary microbiota of healthy participants and those with pneumonia. METHODS: LSFX (75 mg, once a day, orally) was administered to healthy adults (healthy group) and adult patients with pneumonia (pneumonia group), and fecal and saliva samples were collected at five time points (Days 0, 3, 7, 14, and 28). Using the collected samples, α- and ß-diversity indices, as well as bacterial composition of the gut microbiota and salivary microbiota were analyzed using next-generation sequencing. RESULTS: In the healthy group, α-diversity indices of the gut and salivary microbiota were reduced and the lowest values on Day 3. For the gut microbiota, the Chao1 index (richness) recovered on Day 28, whereas the Shannon index (evenness) did not. In the salivary microbiota, the Chao1 and Shannon indices did not recover within the 28 day period. The ß-diversity indices changed after LSFX administration and subsequently recovered on Day 28. After LSFX administration, the abundance of the Lachnospiraceae family decreased in the gut microbiota, and the abundance of Granulicatella, Streptococcus, Prevotella, Absconditabacteriales(SR1), and Saccharimonadales decreased in the salivary microbiota. In the pneumonia group, the α-diversity indices were lowest on Day 14 after LSFX administration. CONCLUSIONS: We elucidated that LSFX administration differentially affected the gut and salivary microbiota; however, the richness and beta diversity recovered within 28 days.

Fatty acid metabolism constrains Th9 cell differentiation and antitumor immunity via the modulation of retinoic acid receptor signaling.

T helper 9 (Th9) cells are interleukin 9 (IL-9)-producing cells that have diverse functions ranging from antitumor immune responses to allergic inflammation. Th9 cells differentiate from naïve CD4+ T cells in the presence of IL-4 and transforming growth factor-beta (TGF-ß); however, our understanding of the molecular basis of their differentiation remains incomplete. Previously, we reported that the differentiation of another subset of TGF-ß-driven T helper cells, Th17 cells, is highly dependent on de novo lipid biosynthesis. On the basis of these findings, we hypothesized that lipid metabolism may also be important for Th9 cell differentiation. We therefore investigated the differentiation and function of mouse and human Th9 cells in vitro under conditions of pharmacologically or genetically induced deficiency of the intracellular fatty acid content and in vivo in mice genetically deficient in acetyl-CoA carboxylase 1 (ACC1), an important enzyme for fatty acid biosynthesis. Both the inhibition of de novo fatty acid biosynthesis and the deprivation of environmental lipids augmented differentiation and IL-9 production in mouse and human Th9 cells. Mechanistic studies revealed that the increase in Th9 cell differentiation was mediated by the retinoic acid receptor and the TGF-ß-SMAD signaling pathways. Upon adoptive transfer, ACC1-inhibited Th9 cells suppressed tumor growth in murine models of melanoma and adenocarcinoma. Together, our findings highlight a novel role of fatty acid metabolism in controlling the differentiation and in vivo functions of Th9 cells.

Lipid metabolism: a central modulator of RORγt-mediated Th17 cell differentiation.

Among the T helper cell subsets, Th17 cells contribute to the development of various inflammatory and autoimmune diseases, including psoriasis, rheumatoid arthritis, inflammatory bowel disease, steroid-resistant asthma, and multiple sclerosis. Retinoid-related orphan receptor gamma t (RORγt), a nuclear hormone receptor, serves as a master transcription factor for Th17 cell differentiation. Recent findings have shown that modulating the metabolic pathway is critical for Th17 cell differentiation, particularly through the engagement of de novo lipid biosynthesis. Suppression of lipid biosynthesis, either through the pharmacological inhibition or gene deletion of related enzymes in CD4+ T cells, results in significant impairment of Th17 cell differentiation. Mechanistic studies indicate that metabolic fluxes through both the fatty acid and cholesterol biosynthetic pathways have a pivotal role in the regulation of RORγt activity through the generation of endogenous RORγt lipid ligands. This review discusses recent discoveries highlighting the importance of lipid metabolism in Th17 cell differentiation and function, as well as exploring specific molecular pathways involved in RORγt activation through cellular lipid metabolism. We further elaborate on a pioneering therapeutic approach to improve inflammatory and autoimmune disorders via the inhibition of RORγt.

The integration of metabolic and proteomic data uncovers an augmentation of the sphingolipid biosynthesis pathway during T-cell differentiation.

Recent studies have highlighted the significance of cellular metabolism in the initiation of clonal expansion and effector differentiation of T cells. Upon exposure to antigens, naïve CD4+ T cells undergo metabolic reprogramming to meet their metabolic requirements. However, only few studies have simultaneously evaluated the changes in protein and metabolite levels during T cell differentiation. Our research seeks to fill the gap by conducting a comprehensive analysis of changes in levels of metabolites, including sugars, amino acids, intermediates of the TCA cycle, fatty acids, and lipids. By integrating metabolomics and proteomics data, we discovered that the quantity and composition of cellular lipids underwent significant changes in different effector Th cell subsets. Especially, we found that the sphingolipid biosynthesis pathway was commonly activated in Th1, Th2, Th17, and iTreg cells and that inhibition of this pathway led to the suppression of Th17 and iTreg cells differentiation. Additionally, we discovered that Th17 and iTreg cells enhance glycosphingolipid metabolism, and inhibition of this pathway also results in the suppression of Th17 and iTreg cell generation. These findings demonstrate that the utility of our combined metabolomics and proteomics analysis in furthering the understanding of metabolic transition during Th cell differentiation.

Organ-Specific Mitochondrial Alterations Following Ischemia-Reperfusion Injury in Post-Cardiac Arrest Syndrome: A Comprehensive Review.

BACKGROUND: Mitochondrial dysfunction, which is triggered by systemic ischemia-reperfusion (IR) injury and affects various organs, is a key factor in the development of post-cardiac arrest syndrome (PCAS). Current research on PCAS primarily addresses generalized mitochondrial responses, resulting in a knowledge gap regarding organ-specific mitochondrial dynamics. This review focuses on the organ-specific mitochondrial responses to IR injury, particularly examining the brain, heart, and kidneys, to highlight potential therapeutic strategies targeting mitochondrial dysfunction to enhance outcomes post-IR injury. METHODS AND RESULTS: We conducted a narrative review examining recent advancements in mitochondrial research related to IR injury. Mitochondrial responses to IR injury exhibit considerable variation across different organ systems, influenced by unique mitochondrial structures, bioenergetics, and antioxidative capacities. Each organ demonstrates distinct mitochondrial behaviors that have evolved to fulfill specific metabolic and functional needs. For example, cerebral mitochondria display dynamic responses that can be both protective and detrimental to neuronal activity and function during ischemic events. Cardiac mitochondria show vulnerability to IR-induced oxidative stress, while renal mitochondria exhibit a unique pattern of fission and fusion, closely linked to their susceptibility to acute kidney injury. This organ-specific heterogeneity in mitochondrial responses requires the development of tailored interventions. Progress in mitochondrial medicine, especially in the realms of genomics and metabolomics, is paving the way for innovative strategies to combat mitochondrial dysfunction. Emerging techniques such as mitochondrial transplantation hold the potential to revolutionize the management of IR injury in resuscitation science. CONCLUSIONS: The investigation into organ-specific mitochondrial responses to IR injury is pivotal in the realm of resuscitation research, particularly within the context of PCAS. This nuanced understanding holds the promise of revolutionizing PCAS management, addressing the unique mitochondrial dysfunctions observed in critical organs affected by IR injury.

Immune cell expression patterns of CD39/CD73 ectonucleotidases in rodent models of cardiac arrest and resuscitation.

Background: Cardiac arrest (CA) is a significant public health concern. There is the high imminent mortality and survival in those who are resuscitated is substantively compromised by the post-CA syndrome (PCAS), characterized by multiorgan ischemia-reperfusion injury (IRI). The inflammatory response in PCAS is complex and involves various immune cell types, including lymphocytes and myeloid cells that have been shown to exacerbate organ IRI, such as myocardial infarction. Purinergic signaling, as regulated by CD39 and CD73, has emerged as centrally important in the context of organ-specific IRI. Hence, comprehensive understanding of such purinergic responses may be likewise imperative for improving outcomes in PCAS. Methods: We have investigated alterations of immune cell populations after CA by utilizing rodent models of PCAS. Blood and spleen were collected after CA and resuscitation and underwent flow cytometry analysis to evaluate shifts in CD3+CD4+ helper T cells, CD3+CD8a+ cytotoxic T cells, and CD4/CD8a ratios. We then examined the expression of CD39 and CD73 across diverse cell types, including myeloid cells, T lymphocytes, and B lymphocytes. Results: In both rat and mouse models, there were significant increases in the frequency of CD3+CD4+ T lymphocytes in PCAS (rat, P < 0.01; mouse, P < 0.001), with consequently elevated CD4/CD8a ratios in whole blood (both, P < 0.001). Moreover, CD39 and CD73 expression on blood leukocytes were markedly increased (rat, P < 0.05; mouse, P < 0.01 at 24h). Further analysis in the experimental mouse model revealed that CD11b+ myeloid cells, with significant increase in their population (P < 0.01), had high level of CD39 (88.80 ± 2.05 %) and increased expression of CD73 (P < 0.05). CD19+ B lymphocytes showed slight increases of CD39 (P < 0.05 at 2h) and CD73 (P < 0.05 at 2h), while, CD3+ T lymphocytes had decreased levels of them. These findings suggested a distinct patterns of expression of CD39 and CD73 in these specific immune cell populations after CA. Conclusions: These data have provided comprehensive insights into the immune response after CA, highlighting high-level expressions of CD39 and CD73 in myeloid cells.

Development and validation of a novel overhead method for anteroposterior radiographs of fractured rat femurs.

We aimed to establish a new method of obtaining femur anteroposterior radiographs from live rats. We used five adult male Sprague-Dawley rats and created a femoral fracture model with an 8 mm segmental fragment. After the surgery, we obtained two femoral anteroposterior radiographs, a novel overhead method, and a traditional craniocaudal view. We obtained the overhead method three times, craniocaudal view once, and anteroposterior radiograph of the isolated femoral bone after euthanasia. We compared the overhead method and craniocaudal view with an isolated femoral anteroposterior view. We used a two-sample t-test and intraclass correlation coefficient (ICC) to estimate the intra-observer reliability. The overhead method had significantly smaller differences than the craniocaudal view for nail length (1.53 ± 1.26 vs. 11.4 ± 3.45, p < 0.001, ICC 0.96) and neck shaft angle (5.82 ± 3.8 vs. 37.8 ± 5.7, p < 0.001, ICC 0.96). No significant differences existed for intertrochanteric length/femoral head diameter (0.23 ± 0.13 vs. 0.23 ± 0.13, p = 0.96, ICC 0.98) or lateral condyle/medial condyle width (0.15 ± 0.16 vs. 0.13 ± 0.08, p = 0.82, ICC 0.99). A fragment displacement was within 0.11 mm (2.4%). The overhead method was closer to the isolated femoral anteroposterior view and had higher reliability.

Therapeutic potential of mitochondrial transplantation in modulating immune responses post-cardiac arrest: a narrative review.

BACKGROUND: Mitochondrial transplantation (MTx) has emerged as a novel therapeutic strategy, particularly effective in diseases characterized by mitochondrial dysfunction. This review synthesizes current knowledge on MTx, focusing on its role in modulating immune responses and explores its potential in treating post-cardiac arrest syndrome (PCAS). METHODS: We conducted a comprehensive narrative review of animal and human studies that have investigated the effects of MTx in the context of immunomodulation. This included a review of the immune responses following critical condition such as ischemia reperfusion injury, the impact of MTx on these responses, and the therapeutic potential of MTx in various conditions. RESULTS: Recent studies indicate that MTx can modulate complex immune responses and reduce ischemia-reperfusion injury post-CA, suggesting MTx as a novel, potentially more effective approach. The review highlights the role of MTx in immune modulation, its potential synergistic effects with existing treatments such as therapeutic hypothermia, and the need for further research to optimize its application in PCAS. The safety and efficacy of autologous versus allogeneic MTx, particularly in the context of immune reactions, are critical areas for future investigation. CONCLUSION: MTx represents a promising frontier in the treatment of PCAS, offering a novel approach to modulate immune responses and restore cellular energetics. Future research should focus on long-term effects, combination therapies, and personalized medicine approaches to fully harness the potential of MTx in improving patient outcomes in PCAS.

Universal Pretreatment Development for Low-input Proteomics Using Lauryl Maltose Neopentyl Glycol.

In recent years, there has been a growing demand for low-input proteomics, particularly in the context of single-cell proteomics (SCP). In this study, we have developed a lauryl maltose neopentyl glycol (LMNG)-assisted sample preparation (LASP) method. This method effectively reduces protein and peptide loss in samples by incorporating LMNG, a surfactant, into the digestion solution and subsequently removing the LMNG simply via reversed phase solid-phase extraction. The advantage of removing LMNG during sample preparation for general proteomic analysis is the prevention of mass spectrometry (MS) contamination. When we applied the LASP method to the low-input SP3 method and on-bead digestion in coimmunoprecipitation-MS, we observed a significant improvement in the recovery of the digested peptides. Furthermore, we have established a simple and easy sample preparation method for SCP based on the LASP method and identified a median of 1175 proteins from a single HEK239F cell using liquid chromatography (LC)-MS/MS with a throughput of 80 samples per day.

IL-27 regulates the differentiation of follicular helper NKT cells via metabolic adaptation of mitochondria.

Invariant natural killer T (iNKT) cells are innate-like T lymphocytes that express an invariant T cell receptor α chain and contribute to bridging innate and acquired immunity with rapid production of large amounts of cytokines after stimulation. Among effecter subsets of iNKT cells, follicular helper NKT (NKTFH) cells are specialized to help B cells. However, the mechanisms of NKTFH cell differentiation remain to be elucidated. In this report, we studied the mechanism of NKTFH cell differentiation induced by pneumococcal surface protein A and α-galactosylceramide (P/A) vaccination. We found that Gr-1+ cells helped iNKT cell proliferation and NKTFH cell differentiation in the spleen by producing interleukin-27 (IL-27) in the early phase after vaccination. The neutralization of IL-27 impaired NKTFH cell differentiation, which resulted in compromised antibody production and diminished protection against Streptococcus pneumoniae infection by the P/A vaccine. Our data indicated that Gr-1+ cell-derived IL-27 stimulated mitochondrial metabolism, meeting the energic demand required for iNKT cells to differentiate into NKTFH cells. Interestingly, Gr-1+ cell-derived IL-27 was induced by iNKT cells via interferon-γ production. Collectively, our findings suggest that optimizing the metabolism of iNKT cells was essential for acquiring specific effector functions, and they provide beneficial knowledge on iNKT cell-mediated vaccination-mediated therapeutic strategies.

Estimating the change in pleural pressure using the change in central venous pressure in various clinical scenarios: a pig model study.

BACKGROUND: We have previously reported a simple correction method for estimating pleural pressure (Ppl) using central venous pressure (CVP). However, it remains unclear whether this method is applicable to patients with varying levels of intravascular volumes and/or chest wall compliance. This study aimed to investigate the accuracy of our method under different conditions of intravascular volume and chest wall compliance. RESULTS: Ten anesthetized and paralyzed pigs (43.2 ± 1.8 kg) were mechanically ventilated and subjected to lung injury by saline lung lavage. Each pig was subjected to three different intravascular volumes and two different intraabdominal pressures. For each condition, the changes in the esophageal pressure (ΔPes) and the estimated ΔPpl using ΔCVP (cΔCVP-derived ΔPpl) were compared to the directly measured change in pleural pressure (Δd-Ppl), which was the gold standard estimate in this study. The cΔCVP-derived ΔPpl was calculated as κ × ΔCVP, where "κ" was the ratio of the change in airway pressure to the change in CVP during the occlusion test. The means and standard deviations of the Δd-Ppl, ΔPes, and cΔCVP-derived ΔPpl for all pigs under all conditions were 7.6 ± 4.5, 7.2 ± 3.6, and 8.0 ± 4.8 cmH2O, respectively. The repeated measures correlations showed that both the ΔPes and cΔCVP-derived ΔPpl showed a strong correlation with the Δd-Ppl (ΔPes: r = 0.95, p < 0.0001; cΔCVP-derived ΔPpl: r = 0.97, p < 0.0001, respectively). In the Bland-Altman analysis to test the performance of the cΔCVP-derived ΔPpl to predict the Δd-Ppl, the ΔPes and cΔCVP-derived ΔPpl showed almost the same bias and precision (ΔPes: 0.5 and 1.7 cmH2O; cΔCVP-derived ΔPpl: - 0.3 and 1.9 cmH2O, respectively). No significant difference was found in the bias and precision depending on the intravascular volume and intraabdominal pressure in both comparisons between the ΔPes and Δd-Ppl, and cΔCVP-derived ΔPpl and Δd-Ppl. CONCLUSIONS: The CVP method can estimate the ΔPpl with reasonable accuracy, similar to Pes measurement. The accuracy was not affected by the intravascular volume or chest wall compliance.

ACC1-mediated fatty acid biosynthesis intrinsically controls thymic iNKT cell development.

To meet the energetic requirements associated with activation, proliferation, and survival, T cells switch their metabolic signatures from energetically quiescent to activated. However, little is known about the role of metabolic pathway controlling the development of invariant natural killer T (iNKT) cells. In the present study, we found that acetyl-CoA carboxylase 1 (ACC1), a rate-limiting enzyme for the fatty acid biosynthesis pathway, plays an essential role in the development of iNKT cells in the thymus. Mice lacking T-cell specific ACC1 showed a reduced number of iNKT cells with an increased proportion of iNKT cells at immature stages 0 and 1. Furthermore, mixed bone marrow (BM) chimera experiments revealed that T-cell intrinsic ACC1 expression was selectively important for the development of thymic iNKT cells, especially for the differentiation of the NKT1 cell subset. Our single-cell RNA-sequencing (scRNA-seq) data and functional analysis demonstrated that ACC1 is responsible for survival of developing iNKT cells. Thus, these findings highlighted a novel role of ACC1 in controlling thymic iNKT cell development mediated by the control of cell survival.

Helicobacter fennelliae Localization to Diffuse Areas of Human Intestine, Japan.

The site of enterohepatic Helicobacter colonization/infection in humans is still unknown. We report microbiologically and histopathologically confirmed H. fennelliae localization in the large intestine in an immunocompromised patient in Japan. This case contributes to better understanding of the life cycle of enterohepatic Helicobacter species.

Performance Evaluation of Matrix Factorization for fMRI Data.

A hypothesis in the study of the brain is that sparse coding is realized in information representation of external stimuli, which has been experimentally confirmed for visual stimulus recently. However, unlike the specific functional region in the brain, sparse coding in information processing in the whole brain has not been clarified sufficiently. In this study, we investigate the validity of sparse coding in the whole human brain by applying various matrix factorization methods to functional magnetic resonance imaging data of neural activities in the brain. The result suggests the sparse coding hypothesis in information representation in the whole human brain, because extracted features from the sparse matrix factorization (MF) method, sparse principal component analysis (SparsePCA), or method of optimal directions (MOD) under a high sparsity setting or an approximate sparse MF method, fast independent component analysis (FastICA), can classify external visual stimuli more accurately than the nonsparse MF method or sparse MF method under a low sparsity setting.

COVID-19-Associated Portal Vein Thrombosis Post-Cholecystitis.

This case study describes a 45-year-old Caucasian male with a past medical history of obesity, hypertension, and non-insulin-dependent diabetes mellitus, who in the setting of coronavirus disease 2019 (COVID-19) pneumonia, developed portal vein thrombosis (PVT) presenting as an acute abdomen after hospital discharge from a cholecystitis episode. PVT is a very infrequent thromboembolic condition, classically occurring in patients with systemic conditions such as cirrhosis, malignancy, pancreatitis, diverticulitis, autoimmunity, and thrombophilia. PVT can cause serious complications, such as intestinal infarction, or even death, if not promptly treated. Due to the limited number of reports in the literature describing PVT in the COVID-19 setting, its prevalence, natural history, mechanism, and precise clinical features remain unknown. Therefore, clinical suspicion should be high for PVT, in any COVID-19 patient who presents with abdominal pain or associated signs and symptoms. To the best of our knowledge, this is the first report of COVID-19-associated PVT causing extensive thrombosis in the portal vein and its right branch, occurring in the setting of early-stage cirrhosis after a preceding episode of cholecystitis.

A Strategic Translational Research System for Drug Discovery in Tottori University.

The probability of successful drug discovery is declining, and research and development costs are increasing. To solve these problems, pharmaceutical companies tend to in-license seeds from venture companies and academia. Therefore, academia's role in drug discovery is extremely important. Tottori University started a "Next-Generation Research Support Project (Strategic Research Support Project)" in 2020, developing a translational research system to promote drug discovery. In this project, we established a research and development infrastructure, such as seed registration, construction of drug research and development support, and research fund allocation. The registered seed were converted into project, and the project implemented this research and development system, and evaluated and verified its results. Twenty-two seeds were converted into projects and portfolios were constructed. Research funds were allocated to eight prioritized projects. Each project raised the research and development stages. From the overall portfolio, one project with the Japan Agency for Medical Research and Development (AMED) Drug Discovery Booster Project, and three projects with Seeds A of the AMED Translational Research Strategic Promotion Program were adopted. Additionally, a new low-molecular weight chaperone drug against GM1-gangliosidosis was out-licensed to an overseas pharmaceutical company. The strength of this system was the strategic allocation of research funds and the accompanying support that leveraged internal and external resources with the PM and researchers at its core. This system achieved certain results in promoting drug discovery; however, resource optimization of specialized personnel needs to be strengthened in the future. In this report, we summarized the efforts of translational research in Japan and around the world. In addition, the translational research efforts of Japanese academia and Tottori University were compared and the current status was summarized.

Evaluation of the Characteristics of Ovarian Endometriomas in Patients with Endometriosis: Efficacy of a Low-Dose Estrogen/Progestogen Combination.

OBJECTIVES: Approximately 17-44% of women diagnosed with endometriosis have ovarian endometriomas (cysts). Although ovarian endometriomas may adversely affect quality of life and work performance, the associations among patient characteristics, cyst size, and pain in women with endometriosis have not yet been reported. Thus, the objective of this study was to assess the association among age, cyst size, and pain in women with ovarian endometriomas. DESIGN: This was a retrospective secondary analysis of pooled data from six randomized clinical trials on the use of low-dose estrogen/progestogen drugs for endometriosis. PARTICIPANTS/MATERIALS, SETTING, AND METHODS: Data on 491 patients enrolled in four randomized and two nonrandomized trials between 2003 and 2017 were pooled. None of the participants had undergone surgical treatment before trial participation. We examined differences in dysmenorrhea score, menstrual pain score, analgesic score, and pelvic pain, as measured using a visual analog scale (VAS), by age and endometrioma size. RESULTS: The mean dysmenorrhea, menstrual pain, and analgesic scores were 4.2, 2.2, and 2.0, respectively. The mean VAS for pelvic pain was 55, which decreased significantly with an increase in age. Age was not associated with endometrioma size, including volume and maximum diameter, or dysmenorrhea score. Additionally, endometrioma volume and maximum diameter were not associated with menstrual pain, analgesic score, or pelvic pain. LIMITATIONS: The details of past treatment history were not available; therefore, these could not be considered in the analysis. Additionally, the assessment of pain is heavily influenced by psychological factors, making it difficult to assess the true extent of pain. CONCLUSIONS: Endometrioma size was not associated with dysmenorrhea or pelvic pain measured using the VAS.

Risk and Prognosis of Upper Extremity Deep Vein Thrombosis.

Objectives: We aimed to investigate the clinical features of upper extremity deep vein thrombosis (UEDVT). Methods: We retrospectively reviewed the background, thrombus site, treatment, and outcome of 76 UEDVT patients. Results: Of the 76 UEDVT patients, 44 (57.9%) were men, and 51 (67.1%) were complicated by malignancy, 44 (57.9%) had an indwelling central vein (CV) catheter, 8 (10.5%) had concomitant pulmonary embolization (PE), and 33 (43.3%) were symptomatic. Regarding the thrombus site, the right internal jugular vein was the most common, with 30 cases (35.3%). As regards the treatment method, 53 patients (69.7%) received oral anticoagulants. In 2015, when direct oral anticoagulants (DOACs) was covered by insurance, there were 44 UEDVT cases, of which 34 (77.3%) received DOACs. Outcomes at a mean observation period of 37.5±41.5 months included 40 deaths (52.6%) with a mean survival of 16.3±21.3 months. The most common cause of death was malignancy, with 33 cases (82.5%). Conclusion: In the background of UEDVT, the combination of indwelling CV catheter placement and malignancy was frequently observed. While the risk of recurrence or PE complications is low, the prognosis of UEDVT complicated by malignancy is extremely poor.