Association of Nilotinib With Cardiovascular Diseases in Patients With Chronic Myelogenous Leukemia: A National Population-Based Cohort Study.

BACKGROUND: Tyrosine kinase inhibitor (TKI) treatment has been identified to be a risk factor for metabolic syndrome and cardiovascular diseases (CVDs) in patients diagnosed with chronic myeloid leukemia (CML). However, the specific contribution of post-TKI metabolic syndrome and the individual TKIs, including imatinib, nilotinib, and dasatinib, contribute to the development of CVDs remains unclear. METHODS: We conducted a nationwide database to investigate the incidence of post-TKI metabolic syndrome, including diabetes, hyperlipidemia, and hypertension, as well as their association with CVDs. To compare the risk of post-TKI comorbidities and CVDs among TKIs, we utilized the incidence rate ratio (IRR), and subdistribution hazard ratio (SHR) calculated from multiple Fine-Gray models. RESULTS: A total of 1211 patients without diabetes, 1235 patients without hyperlipidemia, and 1074 patients without hypertension were enrolled in the study. The incidence rate of post-TKI diabetes and hyperlipidemia was the highest in patients treated with nilotinib compared to imatinib and dasatinib (IRRs ≥ 3.15, Ps ≤ .047). After adjusting for confounders, nilotinib remained a significant risk factor for post-TKI diabetes and hyperlipidemia at an SHR of 3.83 (P < .001) and 5.15 (P < .001), respectively. Regarding the occurrence of CVDs, patients treated with nilotinib were more likely to develop CVDs than those treated with imatinib in non-hyperlipidemic group (IRR = 3.21, P = .020). Pre-existing and post-TKI hyperlipidemia were found to have a stronger association with CVDs, with SHR values of 5.81 (P = .034) and 13.21 (P = .001), respectively. CONCLUSION: The findings of this study indicate that nilotinib treatment is associated with increased risks of diabetes and hyperlipidemia, with hyperlipidemia being the most significant risk for CVDs. Therefore, we recommend that CML patients receiving nilotinib should undergo screening for diabetes and hyperlipidemia prior to initiating TKI treatment. Additionally, regular monitoring of lipid profiles during TKI therapy and implementing effective management strategies to control hyperlipidemia are crucial.

Epidemiology and outcomes of multidrug-resistant bacterial infection in non-cystic fibrosis bronchiectasis.

PURPOSE: Multidrug-resistant (MDR) bacteria impose a considerable health-care burden and are associated with bronchiectasis exacerbation. This study investigated the clinical outcomes of adult patients with bronchiectasis following MDR bacterial infection. METHODS: From the Chang Gung Research Database, we identified patients with bronchiectasis and MDR bacterial infection from 2008 to 2017. The control group comprised patients with bronchiectasis who did not have MDR bacterial infection and were propensity-score matched at a 1:2 ratio. The main outcomes were in-hospital and 3-year mortality. RESULTS: In total, 554 patients with both bronchiectasis and MDR bacterial infection were identified. The types of MDR bacteria that most commonly affected the patients were MDR- Acinetobacter baumannii (38.6%) and methicillin-resistant Staphylococcus aureus (18.4%), Extended-spectrum-beta-lactamases (ESBL)- Klebsiella pneumoniae (17.8%), MDR-Pseudomonas (14.8%), and ESBL-E. coli (7.5%). Compared with the control group, the MDR group exhibited lower body mass index scores, higher rate of chronic bacterial colonization, a higher rate of previous exacerbations, and an increased use of antibiotics. Furthermore, the MDR group exhibited a higher rate of respiratory failure during hospitalization (MDR vs. control, 41.3% vs. 12.4%; p < 0.001). The MDR and control groups exhibited in-hospital mortality rates of 26.7% and 7.6%, respectively (p < 0.001); 3-year respiratory failure rates of 33.5% and 13.5%, respectively (p < 0.001); and 3-year mortality rates of 73.3% and 41.5%, respectively (p < 0.001). After adjustments were made for confounding factors, the infection with MDR and MDR bacteria species were determined to be independent risk factors affecting in-hospital and 3-year mortality. CONCLUSIONS: MDR bacteria were discovered in patients with more severe bronchiectasis and were independently associated with an increased risk of in-hospital and 3-year mortality. Given our findings, we recommend that clinicians identify patients at risk of MDR bacterial infection and follow the principle of antimicrobial stewardship to prevent the emergence of resistant bacteria among patients with bronchiectasis.

Inference for the dimension of a regression relationship using pseudo-covariates.

In data analysis using dimension reduction methods, the main goal is to summarize how the response is related to the covariates through a few linear combinations. One key issue is to determine the number of independent, relevant covariate combinations, which is the dimension of the sufficient dimension reduction (SDR) subspace. In this work, we propose an easily-applied approach to conduct inference for the dimension of the SDR subspace, based on augmentation of the covariate set with simulated pseudo-covariates. Applying the partitioning principal to the possible dimensions, we use rigorous sequential testing to select the dimensionality, by comparing the strength of the signal arising from the actual covariates to that appearing to arise from the pseudo-covariates. We show that under a "uniform direction" condition, our approach can be used in conjunction with several popular SDR methods, including sliced inverse regression. In these settings, the test statistic asymptotically follows a beta distribution and therefore is easily calibrated. Moreover, the family-wise type I error rate of our sequential testing is rigorously controlled. Simulation studies and an analysis of newborn anthropometric data demonstrate the robustness of the proposed approach, and indicate that the power is comparable to or greater than the alternatives.

Non-missile penetrating brain injury-surgical techniques for removing a long penetrating foreign body: a case report.

PURPOSE: Penetrating brain injury (PBI), a relatively uncommon injury, is associated with remarkable secondary complications such as vascular injury, intracranial haemorrhage, infection, and mortality. Non-missile PBI (NMPBI) due to sharp or blunt objects is usually treated surgically by removing the penetrating object, evacuating the associated haemorrhage, identifying possible bleeders along with haemostasis, and performing debridement. Various approaches are used for different scenarios of non-missile PBI according to the object's characteristics, penetrating site, depth, associated intracerebral haemorrhage (ICH), and presence of vascular injury along the penetrating tract. NMPBI cases are rarely reported among civilians. We herein describe a patient who was successfully treated for NMPBI, as well as frontal ICH, by simultaneously removing the heavy, metallic penetrating foreign body. METHODS: We performed corticotomy through a shorter tract instead of a deep penetrating trajectory, which minimizes the extent of damage to the brain and enables immediate management of vascular injury under direct vision while removing the foreign body, and intraoperative sonography, which provides real-time information of the penetrating object and the surrounding brain structure. We did not perform computed tomography angiography and digital subtraction angiography (DSA) because the stab location was at the frontal region, with low risk of vascular injury. Moreover, DSA is time-consuming, which may delay decompressive surgery. RESULTS: The patient was successfully treated through an alternative approach removing the long, heavy, metallic penetrating foreign body and eliminating the accompanying frontal ICH simultaneously. Focal brain abscess developed 8 days after the injury and resolved completely after antibiotics treatment. Dysphasia gradually improved but right distal limbs weakness with spasticity is still present. CONCLUSIONS: Our findings suggest prompt diagnosis by preoperative imaging, screening of vascular injury, decompression with debridement, and antibiotics treatment are important. The alternative surgical approach we proposed is exceptional and should be considered while treating patients with deep NMPBI.

Resection of swollen temporal muscles in patients with intractable intracranial hypertension after decompressive craniectomy.

BACKGROUND: Decompressive craniectomy is employed as treatment for traumatic brain swelling in selected patients. We discussed the effect of temporal muscle resection in patients with intractable intracranial hypertension and temporal muscle swelling after craniectomy. METHODS: Records of 280 craniectomies performed on 258 patients who were admitted with severe head injury were retrospectively reviewed. Eight patients developed intractable increased intracranial pressure with temporal muscle swelling within 24 h after craniectomy and were treated by muscle resection. RESULTS: The initial Glasgow Coma Scale score was 7 ± 1. The mean intracranial pressure was 41.7 ± 8.59 mmHg before muscle resection and 14.81 ± 8.07 mmHg immediately after surgery. Five patients had skull fracture and epidural hematoma at the craniectomy site. The mean intensive care unit stay was 11.25 ± 5.99 days. Glasgow Outcome Scale-Extended scoring performed during the 12-month follow-up visit showed that 6 patients (75%) had a favorable outcome. CONCLUSIONS: Our study findings indicate that a direct impact on the temporal region during trauma may lead to subsequent temporal muscle swelling. Under certain circumstances, muscle resection can effectively control intracranial pressure.

A Miniature Intermittent-Flow Respirometry System with a 3D-Printed, Palm-Sized Zebrafish Treadmill for Measuring Rest and Activity Metabolic Rates.

Zebrafish are a preferred vertebrate model for evaluating metabolism during development, and for toxicity studies. However, commercially available intermittent-flow respirometry systems (IFRS) do not provide a suitable zebrafish-scaled swimming tunnel with a low water volume and proper flow velocities. We developed a miniature IFRS (mIFRS) with a 3D-printed, palm-sized zebrafish treadmill for measuring the swimming ability and metabolic rate of a single one- or three-month-old zebrafish with and without toxicity treatment. The 3D-printed zebrafish treadmill consists of discrete components assembled together which enables the provision of a temporary closed circulating water flow. The results showed that three-month-old zebrafish of normal physiological status had higher energetic efficiency and could swim at a higher critical swimming speed (Ucrit) of 16.79 cm/s with a lower cost of transport (COTopt) of 0.11 µmol g-1m-1. However, for a single three-month-old zebrafish treated with an antibacterial agent, Ucrit decreased to 45% of normal zebrafish and the COTopt increased to 0.24 µmol g-1m-1, due to the impairment of mitochondria. Our mIFRS provides a low-cost, portable, and readily adaptable tool for studying the swimming performance and energetic metabolism of zebrafish.

Bioenergetic Health Assessment of a Single Caenorhabditis elegans from Postembryonic Development to Aging Stages via Monitoring Changes in the Oxygen Consumption Rate within a Microfluidic Device.

Monitoring dynamic changes in oxygen consumption rates (OCR) of a living organism in real time provide an indirect method of monitoring changes in mitochondrial function during development, aging, or malfunctioning processes. In this study, we developed a microfluidic device integrated with an optical detection system to measure the OCR of a single developing Caenorhabditis elegans (C. elegans) from postembryonic development to aging stages in real time via phase-based phosphorescence lifetime measurement. The device consists of two components: an acrylic microwell deposited with an oxygen-sensitive luminescent layer for oxygen (O2) measurement and a microfluidic module with a pneumatically driven acrylic lid to controllably seal the microwell. We successfully measured the basal respiration (basal OCR, in pmol O2/min/worm) of a single C. elegans inside a microwell from the stages of postembryonic development (larval stages) through adulthood to aged adult. Sequentially adding metabolic inhibitors to block bioenergetic pathways allowed us to measure the metabolic profiles of a single C. elegans at key growth and aging stages, determining the following fundamental parameters: basal OCR, adenosine triphosphate (ATP)-linked OCR, maximal OCR, reserve respiratory capacity, OCR due to proton leak, and non-mitochondrial OCR. The bioenergetic health index (BHI) was calculated from these fundamental parameters to assess the bioenergetic health of a single developing C. elegans from the postembryonic development to aging stages. The changes in BHI are correlated to C. elegans development stage, with the highest BHI = 27.5 for 4-day-old adults, which possess well-developed bioenergetic functionality. Our proposed platform demonstrates for the first time the feasibility of assessing the BHI of a single C. elegans from postembryonic development to aging stages inside a microfluidic device and provides the potential for a wide variety of biomedical applications that relate mitochondrial malfunction and diseases.

Synthetic Fluororutaecarpine Inhibits Inflammatory Stimuli and Activates Endothelial Transient Receptor Potential Vanilloid-Type 1.

The natural product, rutaecarpine (RUT), is the main effective component of Evodia rutaecarpa which is a widely used traditional Chinese medicine. It has vasodilation, anticoagulation, and anti-inflammatory activities. However, further therapeutic applications are limited by its cytotoxicity. Thus, a derivative of RUT, 10-fluoro-2-methoxyrutaecarpine (F-RUT), was designed and synthesized that showed no cytotoxicity toward RAW264.7 macrophages at 20 µM. In an anti-inflammation experiment, it inhibited the production of nitric oxide (NO) and tumor necrosis factor (TNF)-α in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages; cyclooxygenase (COX)-2 and inducible NO synthase (iNOS) induced by LPS were also downregulated. After 24 h of treatment, F-RUT significantly inhibited cell migration and invasion of ovarian A2780 cells. Furthermore, F-RUT promoted expressions of transient receptor potential vanilloid type 1 (TRPV1) and endothelial (e)NOS in human aortic endothelial cells, and predominantly reduced the inflammation in ovalbumin/alum-challenged mice. These results suggest that the novel synthetic F-RUT exerts activities against inflammation and vasodilation, while displaying less toxicity than its lead compound.

Increased risk of second primary malignancies following uterine cancer: a population-based study in Taiwan over a 30-year period.

BACKGROUND: Previous studies assessing second primary malignancies (SPMs) after uterine cancer have been conducted in Western populations with conflicting results. This study aimed to define the incidence and risk of SPMs in Taiwanese patients with an initial diagnosis of uterine cancer. METHODS: Using population-based data from the Taiwan Cancer Registry for the period 1979-2008, we quantified standardized incidence ratios (SIRs) among 11,571 women with an initial diagnosis of uterine cancer. RESULTS: Among the 11,571 women, 555 (4.80%) developed at least one SPM during 69,987 person-years of follow-up. There was a 71% increased risk of SPM following uterine cancer (SIR=1.71, 95% CI, 1.57-1.86), with higher risks in the vagina/vulva (SIR=9.06), small intestine (SIR=8.45), ovary (SIR=4.15), urinary bladder (SIR=2.31), kidney (SIR=2.24), colorectum (SIR=2.24), lung (SIR=1.96), and breast (SIR=1.43). The risk of SPM was found to be the highest within the first 5 years after diagnosis of uterine cancer, with surveillance bias possibly contributing to the extremely high risk observed in the first follow-up year. The overall risk and pattern of SPM development observed in this study differed from those previously reported in Western populations, possibly because of the methodology and shorter follow-up period employed in this study. The cumulative incidence of SPMs was significantly higher in older patients (≥50 years) than in younger patients (P<0.001). CONCLUSIONS: To our knowledge, this is the first study in an Asian population to report 71% increased risk in SPMs in women previously diagnosed with uterine cancer. A younger age at diagnosis of uterine cancer conferred an increased risk of second malignancies, and SPMs worsened survivorship in patients who survived uterine cancer.

Light-addressable measurement of in vivo tissue oxygenation in an unanesthetized zebrafish embryo via phase-based phosphorescence lifetime detection.

We have developed a digital light modulation system that utilizes a modified commercial projector equipped with a laser diode as a light source for quantitative measurements of in vivo tissue oxygenation in an unanesthetized zebrafish embryo via phase-based phosphorescence lifetime detection. The oxygen-sensitive phosphorescent probe (Oxyphor G4) was first inoculated into the bloodstream of 48 h post-fertilization (48 hpf) zebrafish embryos via the circulation valley to rapidly disperse probes throughout the embryo. The unanesthetized zebrafish embryo was introduced into the microfluidic device and immobilized on its lateral side by using a pneumatically actuated membrane. By controlling the illumination pattern on the digital micromirror device in the projector, the modulated excitation light can be spatially projected to illuminate arbitrarily-shaped regions of tissue of interest for in vivo oxygen measurements. We have successfully measured in vivo oxygen changes in the cardiac region and cardinal vein of a 48 hpf zebrafish embryo that experience hypoxia and subsequent normoxic conditions. Our proposed platform provides the potential for the real-time investigation of oxygen distribution in tissue microvasculature that relates to physiological stimulation and diseases in a developing organism.

Influence of cyclic heating on physical property and biocompatibility of α- and ß-form gutta-percha.

BACKGROUND/PURPOSE: Thermoplasticized techniques with high temperature and repetitive heating in root canal filling may cause degeneration of gutta-percha, producing cytotoxic byproducts and interfering sealing quality. This study was conducted to investigate the influence of cyclic heating on the physical property and biocompatibility of α- and ß-form gutta-perchas. METHODS: Both α- and ß-form gutta-perchas were submitted to two heating processes: continuous heating and cyclic heating. Continuous heating was carried out by heating the samples up to 300°C and 400°C. The samples were then analyzed by differential scanning calorimetry, differential thermal analysis (DTA), and thermogravimetry. For cyclic heating process, samples were heated from 30°C to 200°C for seven cycles and analyzed with DTA and thermogravimetry. For cell adhesion assay, samples were treated (30°C to 200°C, one and seven cycles), submitted to cell culture and examined by scanning electron microscope. RESULTS: Differential scanning calorimetry and DTA indicated that α-form gutta-percha presented a major endothermic peak at 50-57°C, while ß-form gutta-percha showed two major endothermic peaks at 46-50°C and 60-63°C. Total weight loss of ß-form gutta-percha was about 2-fold greater than that of α-form gutta-percha after continuous heating up to 300°C, or cyclic heating for seven times. Scanning electron microscopy showed no obvious difference of cell adhesion on α- and ß-form samples, even with seven cyclic heating or one heating cycle. However, the attachment of the cells to the culture plate (the control) is better than to the gutta-percha samples. CONCLUSION: The increase of heating cycles for α- and ß-form gutta-percha exerts no adverse influence on their biocompatibility. Because the physical property of ß-form gutta-percha becomes unstable when it is heated at over 300°C or subjected to cyclic heating, ß-form gutta-percha may not be recommended for use in thermoplasticized gutta-percha techniques.

Major adverse cardiovascular events in advanced-stage lung cancer: a multicenter cohort study.

Background: Lung cancers are common worldwide. First-line targeted therapy and chemotherapy are both standard treatments in the current guidelines. With the development of new anticancer therapy, the lifespan of patients with late-stage lung cancer has increased. Cardiovascular events can occur during cancer treatment. This observational study aimed to report the incidence of major adverse cardiovascular events (MACE) after cancer treatment using real-world data. Objectives: Patients diagnosed with advanced-stage lung cancer between January 2011 and December 2017 were enrolled. Data were collected from the Chang Gung Research Database (CGRD). Design: Retrospective cohort study. Methods: Baseline characteristics, clinical stages, pathologies, and outcomes were retrieved from the CGRD. Results: We identified 4406 patients with advanced lung cancer, of whom 2197 received first-line epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapy and 2209 received first-line platinum-based chemotherapy. Most patients in the first-line EGFR-TKI group were never-smokers (74.9%), whereas those in the first-line chemotherapy group were ever-smokers (66.0%). The incidence of MACE was not significantly different between the two groups (12.0% versus 11.9%, p = 0.910). However, the incidence of ischemic stroke was higher in the first-line EGFR-TKI group than in the first-line chemotherapy group (3.9% versus 1.9%, p < 0.001). Conclusion: MACEs are common in patients with advanced-stage lung cancer during treatment. The incidence of MACE was similar between the first-line EGFR-TKI therapy and first-line chemotherapy groups. Although more patients in the EGFR-TKI group were female and never-smokers, the risk of ischemic stroke was higher in patients who received first-line EGFR-TKI therapy than in those who received first-line chemotherapy.

Light-addressed electrodeposition of enzyme-entrapped chitosan membranes for multiplexed enzyme-based bioassays using a digital micromirror device.

This paper describes a light-addressed electrolytic system used to perform an electrodeposition of enzyme-entrapped chitosan membranes for multiplexed enzyme-based bioassays using a digital micromirror device (DMD). In this system, a patterned light illumination is projected onto a photoconductive substrate serving as a photo-cathode to electrolytically produce hydroxide ions, which leads to an increased pH gradient. The high pH generated at the cathode can cause a local gelation of chitosan through sol-gel transition. By controlling the illumination pattern on the DMD, a light-addressed electrodeposition of chitosan membranes with different shapes and sizes, as well as multiplexed micropatterning, was performed. The effect of the illumination time of the light pattern on the dimensional resolution of chitosan membrane formation was examined experimentally. Moreover, multiplexed enzyme-based bioassay of enzyme-entrapped chitosan membranes was also successfully demonstrated through the electrodeposition of the chitosan membranes with various shapes/sizes and entrapping different enzymes. As a model experiment, glucose and ethanol were simultaneously detected in a single detection chamber without cross-talk using shape-coded chitosan membranes entrapped with glucose oxidase (GOX), peroxidase (POD), and Amplex Red (AmR) or alcohol oxidase (AOX), POD, and AmR by using same fluorescence indicator (AmR).

Suramin ameliorates osteoarthritis by acting on the Nrf2/HO-1 and NF-κB signaling pathways in chondrocytes and promoting M2 polarization in macrophages.

Osteoarthritis (OA)-the most prevalent of arthritis diseases-is a complicated pathogenesis caused by cartilage degeneration and synovial inflammation. Suramin has been reported to enhance chondrogenic differentiation. However, the therapeutic effect of suramin on OA-induced cartilage destruction has remained unclear. Suramin is an anti-parasitic drug that has potent anti-purinergic properties. This study investigated the protective effects and underlying mechanisms of suramin on articular cartilage degradation using an in vitro study and mice model with post-traumatic OA. We found that suramin markedly suppressed the IL-1ß increased expression of matrix destruction proteases-such as ADAMT4, ADAMTS5, MMP3, MMP13, and inflammatory mediators-including the iNOS, COX2, TNFα, and IL-1ß; while greatly enhancing the synthesis of cartilage anabolic factors-such as COL2A1, Aggrecan and SOX9 in IL-1ß-induced porcine chondrocytes. In vivo experiments showed that intra-articular injection of suramin ameliorated cartilage degeneration and inhibited synovial inflammation in an anterior cruciate ligament transection (ACLT)-induced OA mouse model. In mechanistic studies, we found that exogenous supplementation of suramin can activate Nrf2, and accordingly inhibit the nuclear factor kappa-light-chain-enhancer of activated B cells (NF- κB) and mitogen-activated protein kinase (MAPK) pathways, thereby alleviating the inflammation and ECM degeneration of chondrocytes stimulated by IL-1ß. In addition, suramin also repolarized M1 macrophages to the M2 phenotype, further reducing the apoptosis of chondrocytes. Collectively, the results of the study suggests that suramin is a potential drugs which could serve as a facilitating drug for the application of OA therapy toward clinical treatment.

Real-world patient characteristics and treatment patterns of polycythemia vera in Taiwan between 2016 and 2017: a nationwide cross-sectional study.

Background: Polycythemia vera (PV) patients often experience constitutional symptoms and are at risk of thromboembolism as well as disease progression to myelofibrosis or acute myeloid leukemia. Not only is PV often overlooked but treatment options are also limited, however. Objectives: To explore the patient characteristics and treatment pattern of PV patients in Taiwan, and compare with other countries reported in the literature. Design: This is a nationwide cross-sectional study. Methods: The National Health Insurance Research Database in Taiwan, which covers 99% of the population, was utilized. Patients were identified during the cross-sectional period between 2016 and 2017, and their retrospective data were retrieved from 2001 to 2017. Results: A total of 2647 PV patients were identified between 1 January 2016 and 31 December 2017. This study described the demographic information of these patients, including number of patients by risk stratification and by sex, age at diagnosis, age at cross-sectional period, rate of bone marrow aspiration/biopsy at diagnosis, comorbidities, number of postdiagnosis thrombosis, number of disease progression, and death. The mortality rate of PV patients (4.1%) over 60 of age was higher than the general population of the same age group (2.8%). This study also compared the different treatment patterns between sexes and risk groups. Hydroxyurea was deferred to an older age, but conversely was prescribed at higher dose to younger patients. Alarmingly, a high proportion of patients did not receive phlebotomy or hydroxyurea for at least 2 years. Furthermore, discrepancies in prevalence, age at diagnosis, sex ratio, incidence of thrombosis and mortality were also found when compared with data reported in other countries. Conclusion: The clinical landscape of PV in Taiwan between 2016 and 2017 was examined. Distinctive patterns of phlebotomy and hydroxyurea were identified. Overall, these findings highlight the importance of understanding the patient characteristics and treatment patterns of PV in different regions to better inform clinical practice and improve patient outcomes.

Active endocytosis and microtubule remodeling restore compressed pyramidal neuron morphology in rat cerebral cortex.

Previous studies have shown that compression alone reduced the thickness of rat cerebral cortex and apical dendritic lengths of pyramidal neurons without apparent cell death. Besides, decompression restored dendritic lengths at different degrees depending on duration of compression. To understand the mechanisms regulating dendritic shortening and lengthening upon compression and decompression, we applied transmission electron microscopy to examine microtubule and membrane structure of pyramidal neurons in rat sensorimotor cortex subjected to compression and decompression. Microtubule densities within apical dendritic trunks decreased significantly and arranged irregularly following compression for a period from 30 min to 24 h. In addition, apical dendritic trunks showed twisted contour. Two reasons are accounted for the decrease of microtubule density within this period. First, microtubule depolymerized and resulted in lower number of microtubules. Second, the twisted membrane widened the diameters of apical dendritic trunks, which also caused a decrease in microtubule density. Interestingly, these compression-induced changes were quickly reversed to control level following decompression, suggesting that these changes were accomplished passively. Furthermore, microtubule densities were restored to control level and the number of endocytotic vesicles significantly increased along the apical dendritic membrane in neurons subjected to 36 h or longer period of compression. However, decompression did not make significant changes on dendrites compressed for 36 h, for they had already shown straight appearance before decompression. These results suggest that active membrane endocytosis and microtubule remodeling occur in this adaptive stage to make the apical dendritic trunks regain their smooth contour and regular microtubule arrangement, similar to that of the normal control neurons.

Risk of second primary malignancies in women with cervical cancer: a population-based study in Taiwan over a 30-year period.

OBJECTIVE: Studies conducted in Western countries have reported an increased risk for second primary malignancies after cervical cancer. There is little documentation of ethnic differences in this increased risk, and most of the Asian studies are hospital-based studies with small case numbers. METHODS: Using population-based data from the Taiwan Cancer Registry for the period 1979-2008, we quantified standardized incidence ratios (SIRs) among 52,972 women with initial diagnoses of cervical cancer. RESULTS: Among the 52,972 women, 3061 (5.78%) developed second primary cancers during 433,571 person-years of follow-up. Overall, the SIR for developing a subsequent second cancer was significantly greater than that of the general population (1.36 [95% CI, 1.32-1.41]). There was a greater risk for cancers of the esophagus, stomach, small intestine, rectum, lung, bone, non-melanoma skin, uterine corpus, vagina/vulva, bladder, kidney, and leukemia. When further examining age at diagnosis of cervical cancer (<50 and ≥50) for these 12 sites, we found that the risk of second cancers (SIR, <50 and ≥50: 3.08 vs. 1.63) was higher not only in younger patients, except for non-melanoma skin cancer and endometrial cancer, but also within the first 5 years after diagnosis of cervical cancer. The median overall survival for women with cervical cancer was 18.58 years. The second cancers had a negative impact on overall survival after adjusting for age (P<0.001). CONCLUSIONS: SIR for second cancers was significantly greater than the general population in cervical cancer patients. A young age at the diagnosis of cervical cancer predicted an increased risk. The second cancers worsened overall survival.

Modified Mitchell osteotomy with screw fixation for correction of hallux valgus.

BACKGROUND: The authors have performed more than 1500 cases of a Mitchell osteotomy and traditionally used two crossed pins for fixation. The previous series showed some complications related to pin tract infection, pin migration, and transfer metatarsalgia. Since 2009, the authors have used a compression screw for fixation and made some technical modifications and the results are reported in this article. METHODS: A total of 95 patients underwent a Mitchell ostotomy to correct hallux valgus deformity with fixation with multi-use compression (MUC) screws. Hallux valgus angle (HVA), intermetatarsal angle (IMA), the American Orthopaedic Foot and Ankle Society (AOFAS) hallux metatarsophalangeal-interphalangeal scale were measured preoperatively and postoperatively. RESULTS: ~There were statistically differences between the preoperatively and postoperatively HVA, first IMA, and AOFAS hallux metatarsophalangeal-interphalangeal scores. Five patients (8/137 feet, 5.8%) underwent removal of the screw because of screw tip irritation. Eight patients (9/137 feet, 6.5%) had transfer metatarsalgia of the second metatarsal, with two of them caused by dorsal tilt of the metatarsal head. One patient (1/137 feet, 0.7%) had undercorrection. There was no superficial infection, deep infection, nonunion, or osteonecrosis of the first metatarsal head. CONCLUSION: On the basis of the results observed in this study, it appears that the use of a multi-use compression screw provides satisfactory stabilization of the modified Mitchell osteotomy and was not associated with any serious complications. The modified technique also helped reduce transfer metatarsalgia.

Arthroscopic Partial Trapeziectomy for Thumb Carpometacarpal Joint Osteoarthritis: 5-Year Follow-up.

Osteoarthritis of the thumb carpometacarpal (CMC) joint is the most common type of arthritis of the hand. The goal of the study was to evaluate clinical results and radiographic changes after arthroscopic partial trapeziectomy combined with ligament shrinkage and K-wire fixation to treat thumb CMC joint arthritis. From February 2013 to March 2014, 24 patients with thumb CMC joint arthritis received this arthroscopic procedure. We investigated the preoperative and postoperative Modified Mayo Wrist Score (MMWS); Disabilities of the Arm, Shoulder and Hand (DASH) score; radiographic changes; and associated complications. Sixteen patients completed 5 years of functional score and radiographic follow-up. Comparison of preoperative and postoperative MMWS and DASH scores showed significant improvement after the arthroscopic procedure. Pre-operative and postoperative evaluation of radiographic changes showed significant differences in the CMC joint distance, scaphoid-metacarpal distance, trapezium-metacarpal distance, and metacarpal prominence distance. This arthroscopic procedure is an effective and less invasive method for the treatment of CMC joint arthritis. This procedure can improve clinical function, preserve the mechanical height of the trapezium, and increase CMC joint space. We report our surgical technique and some pitfalls that required attention during the arthroscopic procedure. [Orthopedics. 2022;45(3):e140-e147.].

Different impacts of common risk factors associated with thrombocytopenia in patients with hepatitis B virus and hepatitis C virus infection.

BACKGROUND: Thrombocytopenia is a common extrahepatic manifestation in chronic liver disease. However, there have been rare studies of impacts of risk for hepatitis C virus-associated thrombocytopenia (HCV-TP) and hepatitis B virus-associated thrombocytopenia (HBV-TP). The aim of this study is to evaluate different impacts of risk factors for HCV-TP and HBV-TP. METHODS: We retrospectively collected 1803 HCV patients and 1652 HBV patients to examine the risk factors for time to moderate and severe thrombocytopenia (platelet counts <100 × 109/L and <50 × 109/L, respectively) by Cox proportional hazards models. Moreover, we prospectively enrolled 63 HCV-TP patients, 11 HBV-TP patients, and 27 HCV controls to detect specific antiplatelet antibodies by enzyme-linked immunosorbent assay and analyze their effects. RESULTS: Prevalence of platelet <100 × 109/L was 11.86% and 6.35% in HCV and HBV patients without cancer history, respectively. HCV-to-HBV incidence rate ratio for thrombocytopenia was 6.95. Initial thrombocytopenia was the most significant risk factor for HCV-TP and HBV-TP regardless of thrombocytopenia severity. Splenomegaly and cirrhosis were significant risk factors for moderate, but not severe HCV-TP. Hyperbilirubinemia was an important moderate and severe HBV-TP risk factor. Antiplatelet antibodies were correlated with HCV-TP severity, of which anti-glycoprotein IIb/IIIa antibody being associated with smaller spleen size. The antiplatelet autoantibody might contribute to thrombocytopenia either independently or with splenomegaly as the important risk in HCV-TP patients without advanced cirrhosis. CONCLUSION: HCV was associated with higher thrombocytopenia incidence than HBV. Thrombocytopenia risk factors varied with virus type and severity. Different management for HCV-TP and HBV-TP was suggested.