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1.
Int J Spine Surg ; 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38744483

RESUMO

BACKGROUND: Atlantoaxial transarticular fixation, also called the Magerl technique, is said to be the most robust biomechanical method of fixation of the atlantoaxial vertebrae. However, the procedure carries a risk of spinal cord and vertebral artery injury during the insertion process, especially in patients with a high-riding vertebral artery. In this study, a computed tomography (CT)-based navigation system was used for preoperative planning and insertion. This investigation sought to determine the rate and direction of screw perforation as well as the incidence of screw loosening in computer-assisted atlantoaxial transarticular fixation. METHODS: Sixty patients (31 men and 29 women; mean ± SD age: 65.3 ± 19.6 years) who received atlantoaxial transarticular screw insertion with preoperative CT navigation were analyzed. We investigated screw position and loosening by CT at the final follow-up. RESULTS: Of the 108 screws inserted, the rate of Grade 2 or higher perforation was 4.6% (5/108). Nine of 81 (11.1%) screws inserted into the 44 patients who were followed for at least 6 months showed loosening. Logistic regression analysis revealed that unilateral insertion (odds ratio: 8.50, 95% confidence interval: 1.53-47.2, P = 0.014) was significantly associated with the incidence of screw loosening. CONCLUSIONS: The screw perforation rate of Grade 2 or higher in computer-assisted atlantoaxial transarticular screw fixation was 4.6%, with comparable frequencies of perforation direction. Unilateral insertion was a significant independent factor associated with screw loosening, which occurred in 11.1% of insertions. CLINICAL RELEVANCE: Spine surgeons should follow up with patients with caution because screws with unilateral insertion are prone to loosening.

2.
Biol Pharm Bull ; 47(5): 895-903, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38692865

RESUMO

Epidermal growth factor (EGF)-EGF receptor (EGFR) signaling studies paved the way for a basic understanding of growth factor and oncogene signaling pathways and the development of tyrosine kinase inhibitors (TKIs). Due to resistance mutations and the activation of alternative pathways when cancer cells escape TKIs, highly diverse cell populations form in recurrent tumors through mechanisms that have not yet been fully elucidated. In this review, we summarize recent advances in EGFR basic research on signaling networks and intracellular trafficking that may clarify the novel mechanisms of inhibitor resistance, discuss recent clinical developments in EGFR-targeted cancer therapy, and offer novel strategies for cancer drug development.


Assuntos
Antineoplásicos , Receptores ErbB , Neoplasias , Inibidores de Proteínas Quinases , Transdução de Sinais , Humanos , Receptores ErbB/metabolismo , Receptores ErbB/antagonistas & inibidores , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Transdução de Sinais/efeitos dos fármacos , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/farmacologia , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologia , Animais , Resistencia a Medicamentos Antineoplásicos , Terapia de Alvo Molecular/métodos
3.
ESC Heart Fail ; 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627993

RESUMO

AIMS: This study aimed to elucidate age-stratified clinical profiles and outcomes in patients with heart failure (HF) with preserved left ventricular ejection fraction (LVEF) (HFpEF). METHODS AND RESULTS: The Chronic Heart Failure Registry and Analysis in the Tohoku District-2 (CHART-2) Study included 2824 consecutive HFpEF patients with LVEF ≥ 50% (mean age 69.0 ± 12.3 years; 67.7% male) with a median follow-up of 9.8 years. We stratified them into five age groups: ≤54 (N = 349, 12.4%), 55-64 (N = 529, 18.7%), 65-74 (N = 891, 31.6%), 75-84 (N = 853, 30.2%), and ≥85 years (N = 202, 7.2%), and we categorized these age groups into younger (≤64 years) and older (≥65 years) groups. We compared the clinical profiles and outcomes of HFpEF patients across age groups. Younger HFpEF groups exhibited a male predominance, elevated body mass index (BMI), and poorly controlled diabetes (haemoglobin A1c > 7.0%). Older HFpEF groups were more likely to be female with multiple comorbidities, including coronary artery disease, hypertension, renal impairment, and atrial fibrillation. The positive association between elevated BMI and HFpEF was more pronounced with lower classes of age from ≥85 to ≤54 years, especially in males. With higher classes of age from ≤54 to ≥85 years, mortality rates increased, and HF death became proportionally more prevalent (Ptrend < 0.001), whereas sudden cardiac death (SCD) exhibited the opposite trend (Ptrend = 0.002). Poorly controlled diabetes emerged as the only predictor of SCD in the younger groups (adjusted hazard ratio 4.26; 95% confidence interval 1.45-12.5; P = 0.008). Multiple comorbidities were significantly associated with an increased risk of HF-related mortality in the older groups. CONCLUSIONS: Younger HFpEF patients (≤64 years) exhibit a male predominance, elevated BMI, and poorly controlled diabetes, highlighting the importance of glycaemic control in reducing SCD risk. Older HFpEF patients (≥65 years) are more likely to be female, with multiple comorbidities linked to an increased risk of HF-related mortality. These findings underscore the need for physicians to recognize age-related, distinct HFpEF phenotypes for personalized patient management.

4.
Eur Spine J ; 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38573386

RESUMO

PURPOSE: Preoperative computed tomography (CT)-based navigation is used for cervical pedicle screw (CPS) insertion to mitigate the risk of spinal cord and vertebral artery injury. In vertebrae with osteosclerosis due to degeneration or other factors, however, probing may not proceed easily, with difficulty creating the CPS insertion hole. This study investigated the impact of osteosclerosis on the accuracy of CPS insertion. METHODS: A total of 138 patients with CPS inserted at the C3-C7 level using preoperative CT navigation were retrospectively analyzed. Pre- and postoperative CT was employed to investigate screw position and Hounsfield unit (HU) values at the lateral mass to evaluate the degree of osteosclerosis in the CPS insertion pathway. RESULTS: Among 561 CPS insertions, the Grade 3 perforation rate was 1.8%, and the Grade 2 or higher perforation rate was 8.0%. When comparing insertions with and without CPS perforation, HU values were significantly higher in the perforation group (578 ± 191 vs. 318 ± 191, p < 0.01). The frequency of CPS insertion into the mid-cervical spine was also significantly greater in the perforation group (68.9% vs. 62.5%, p < 0.01). Logistic regression analysis revealed that a high HU value at the lateral mass (odds ratio 1.09, 95% confidence interval: 1.07-1.11, p < 0.01) was a significant independent factor associated with CPS deviation. CONCLUSIONS: The screw perforation rate of Grade 2 or higher in CPS insertion using preoperative CT-based navigation was 8.0%. Since osteosclerosis was an independent factor related to CPS deviation, additional care may be required during insertion into affected vertebrae.

5.
Circ J ; 2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38684394

RESUMO

BACKGROUND: Women with acute myocardial infarction (AMI) often present a worse risk profile and experience a higher rate of in-hospital mortality than men. However, sex differences in post-discharge prognoses remain inadequately investigated. We examined the impact of sex on 1-year post-discharge outcomes in patients with AMI undergoing percutaneous coronary intervention.Methods and Results: We extracted patient-level data for the period January 2017-December 2018 from the J-PCI OUTCOME Registry, endorsed by the Japanese Association of Cardiovascular Intervention and Therapeutics. One-year all-cause and cardiovascular mortality and major adverse cardiovascular events were compared between men and women. In all, 29,856 AMI patients were studied, with 6,996 (23.4%) being women. Women were significantly older and had a higher prevalence of comorbidities than men. Crude all-cause mortality was significantly higher among women than men (7.5% vs. 5.4% [P<0.001] for ST-elevation myocardial infarction [STEMI]; 7.0% vs. 5.2% [P=0.006] for non-STEMI). These sex-related differences in post-discharge outcomes were attenuated after stratification by age. Multivariate analysis demonstrated an increase in all-cause mortality in both sexes with increasing age and advanced-stage chronic kidney disease (CKD). CONCLUSIONS: Within this nationwide cohort, women had worse clinical outcomes following AMI than men. However, these sex-related differences in outcomes diminished after adjusting for age. In addition, CKD was significantly associated with all-cause mortality in both sexes.

6.
ESC Heart Fail ; 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38685603

RESUMO

AIMS: The incidence and prognosis of symptomatic heart failure following acute myocardial infarction (AMI) in the primary percutaneous coronary intervention era have rarely been reported in the literature. This study aimed to (i) determine the incidence of heart failure admission among AMI survivors, (ii) compare 1 year outcomes between patients with heart failure admission and those without, and (iii) identify the independent risk factors associated with heart failure admission. METHODS AND RESULTS: The Japan Acute Myocardial Infarction Registry is a prospective multicentre registry from which data on consecutively enrolled patients with AMI from 50 institutions between 2015 and 2017 were obtained. Among the 3411 patients enrolled, 3226 who survived until discharge were included in this study. The primary endpoint was all-cause mortality. The secondary endpoints were major adverse cardiovascular events (defined as cardiovascular mortality, non-fatal myocardial infarction, or non-fatal cerebral infarction) and major bleeding events corresponding to Bleeding Academic Research Consortium Type 3 or 5. Clinical outcomes were compared between the patients who were and were not admitted for heart failure. Over a median follow-up of 12 months, 124 patients (3.8%) were admitted due to heart failure. Independent risk factors for heart failure admission included older age, female sex, Killip class ≥2 on admission, left ventricular ejection fraction <40%, estimated glomerular filtration rate ≤30 mL/min/1.73 m2, a history of malignancy, and non-use of angiotensin-converting enzyme inhibitors at discharge. The cumulative incidence of all-cause mortality was significantly higher in the heart failure admission group than in the no heart failure admission group (11.3% vs. 2.5%, P < 0.001). The rates of major adverse cardiovascular events (16.9% vs. 2.7%, P < 0.001) and major bleeding (6.5% vs. 1.6%, P < 0.001) were significantly higher in the heart failure admission group. Heart failure admission was associated with a higher risk of all-cause mortality, even after adjusting for potential confounders (adjusted hazard ratio: 2.41, 95% confidence interval: 1.33-4.39, P = 0.004). CONCLUSIONS: Utilizing real-world data of the contemporary percutaneous coronary intervention era from the Japan Acute Myocardial Infarction Registry database, this study demonstrates that the heart failure admission of AMI survivors was significantly associated with higher all-cause mortality rates.

7.
Cell Rep ; 43(4): 114104, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38602872

RESUMO

Clinical evidence has revealed that high-level activation of NRF2 caused by somatic mutations in NRF2 (NFE2L2) is frequently detected in esophageal squamous cell carcinoma (ESCC), whereas that caused by somatic mutations in KEAP1, a negative regulator of NRF2, is not. Here, we aspire to generate a mouse model of NRF2-activated ESCC using the cancer-derived NRF2L30F mutation and cancer driver mutant TRP53R172H. Concomitant expression of NRF2L30F and TRP53R172H results in formation of NRF2-activated ESCC-like lesions. In contrast, while squamous-cell-specific deletion of KEAP1 induces similar NRF2 hyperactivation, the loss of KEAP1 combined with expression of TRP53R172H does not elicit the formation of ESCC-like lesions. Instead, KEAP1-deleted cells disappear from the esophageal epithelium over time. These findings demonstrate that, while cellular NRF2 levels are similarly induced, NRF2 gain of function and KEAP1 loss of function elicits distinct fates of squamous cells. The NRF2L30F mutant mouse model developed here will be instrumental in elucidating the mechanistic basis leading to NRF2-activated ESCC.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Proteína 1 Associada a ECH Semelhante a Kelch , Fator 2 Relacionado a NF-E2 , Fator 2 Relacionado a NF-E2/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Animais , Camundongos , Carcinoma de Células Escamosas do Esôfago/metabolismo , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/genética , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/genética , Humanos , Proteína Supressora de Tumor p53/metabolismo , Proteína Supressora de Tumor p53/genética , Mutação com Ganho de Função , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/genética , Mutação com Perda de Função
8.
J Parkinsons Dis ; 14(3): 415-435, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38457149

RESUMO

Parkinson's disease (PD) is an increasingly prevalent neurological disorder, affecting more than 8.5 million individuals worldwide. α-Synucleinopathy in PD is considered to cause dopaminergic neuronal loss in the substantia nigra, resulting in characteristic motor dysfunction that is the target for current medical and surgical therapies. Standard treatment for PD has remained unchanged for several decades and does not alter disease progression. Furthermore, symptomatic therapies for PD are limited by issues surrounding long-term efficacy and side effects. Cell replacement therapy (CRT) presents an alternative approach that has the potential to restore striatal dopaminergic input and ameliorate debilitating motor symptoms in PD. Despite promising pre-clinical data, CRT has demonstrated mixed success clinically. Recent advances in graft biology have renewed interest in the field, resulting in several worldwide ongoing clinical trials. However, factors surrounding the effective neurosurgical delivery of cell grafts have remained under-studied, despite their significant potential to influence therapeutic outcomes. Here, we focus on the key neurosurgical factors to consider for the clinical translation of CRT. We review the instruments that have been used for cell graft delivery, highlighting current features and limitations, while discussing how future devices could address these challenges. Finally, we review other novel developments that may enhance graft accessibility, delivery, and efficacy. Challenges surrounding neurosurgical delivery may critically contribute to the success of CRT, so it is crucial that we address these issues to ensure that CRT does not falter at the final hurdle.


Assuntos
Neurônios Dopaminérgicos , Doença de Parkinson , Humanos , Doença de Parkinson/terapia , Animais
9.
No Shinkei Geka ; 52(2): 380-388, 2024 Mar.
Artigo em Japonês | MEDLINE | ID: mdl-38514128

RESUMO

Surgical extirpation of brain arteriovenous malformations(AVMs)requires precise pre-surgical simulation. Utilizing image software, widely used with picture archiving and communication systems(PACS), surgeons can generate simulation images that precisely illustrate the proper feeders, passing arteries, and drainers. The crucial steps for creating informative simulation images include: (1)the free rotation of reconstructed 3D digital subtraction angiography(DSA)images; (2)removal of irrelevant arteries(the most important procedure); and(3)construction of stereo imagery of the "core images." This article presents a detailed description of these procedures.


Assuntos
Malformações Arteriovenosas Intracranianas , Humanos , Malformações Arteriovenosas Intracranianas/diagnóstico por imagem , Malformações Arteriovenosas Intracranianas/cirurgia , Imageamento Tridimensional/métodos , Angiografia Digital/métodos , Artérias , Encéfalo/diagnóstico por imagem
10.
J Orthop Sci ; 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38519378

RESUMO

INTRODUCTION: Hip fractures are commonly associated with osteoporosis and pose a risk for secondary fractures. Although the administration of anti-osteoporotic drugs is recommended after fractures to mitigate this risk, the potential effect of strong anti-resorptive drugs (e.g., denosumab) on fracture healing processes have not been extensively studied. This prospective study aimed to evaluate the feasibility of early denosumab administration after femoral intertrochanteric fracture surgery and to compare its effect on fracture healing to that of bisphosphonate-treated patients. MATERIALS AND METHODS: Patients who underwent surgery for intertrochanteric femoral fragility fractures between November 2018 and November 2020 were prospectively examined. Patients were randomized into two groups (denosumab [DSM] and ibandronate [IBN] groups) using a simple randomization procedure. Physical findings, plain radiographs, and computed tomography (CT) were used to evaluate fracture healing at 3 months postoperatively. RESULTS: Physical findings showed no significant differences between the two groups in pain on loading, tenderness at fracture site, or walking ability. There were inter-rater differences in radiological fracture healing rate: plain radiographs, 57.5%-81.8% in the DSM group and 51.5%-90.9% in the IBN group; CT, 51.5%-72.7% in the DSM group and 45.4%-81.8% in the IBN group. Although there were variations, there were no significant differences in the fracture healing rate between groups on plain radiographs or CT among all three raters. CONCLUSIONS: Early administration of denosumab after intertrochanteric femoral fracture surgery did not delay radiological or clinical fracture healing times when compared with ibandronate administration.

11.
Sci Rep ; 14(1): 5602, 2024 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-38453997

RESUMO

This investigation examined the clinical implications of mild vertebral fractures in older community-dwelling residents. Focusing on the locomotion health of older individuals, the earlier reported Obuse study enrolled 415 randomly sampled Japanese residents aged between 50 and 89 years, 411 of whom underwent X-ray evaluations for pre-existing vertebral fractures. A blinded assessment of vertebral fractures based on Genant's criteria was conducted on the T5-L5 spine for rating on a severity scale. Grade 1 mild fractures were not linked to age in males, but increased with aging in females. Female participants had fewer Grade 1 and 2 fractures (P = 0.003 and 0.035, respectively) but more Grade 3 fractures (P = 0.013) than did males independently of age (Grade 1, 2, and 3: 25%, 16%, and 9% in females and 40%, 22%, and 6% in males, respectively). Weak negative correlations were observed between the number of fractures and bone mineral density in females for all fracture grades (Spearman's rho: 0.23 to 0.36, P < 0.05). Our study showed that Grade 1 mild vertebral fractures in males lacked pathological significance, while in females they potentially indicated fragility fractures and were related to poor lumbopelvic alignment.


Assuntos
Vida Independente , Fraturas da Coluna Vertebral , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Fatores de Risco , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/epidemiologia , Coluna Vertebral , Densidade Óssea
12.
J Wound Care ; 33(Sup3a): lxi-lxviii, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38457269

RESUMO

OBJECTIVE: The use of 2-octyl cyanoacrylate with polyester mesh (OCA-M) has become common in total hip and knee arthroplasty (THA, TKA). We aimed to compare the safety and cosmetic outcomes between OCA-M and standard suture techniques and staples, and determine whether OCA-M can safely be used for TKA. METHOD: Inclusion criteria were patients who underwent THA or TKA from January 2010 to October 2011 (Suture group), November 2011 to August 2013 (Staple group), March 2017 to September 2018 (OCA-M group). Exclusion criteria was loss of imaging data. Complications during hospitalisation (early complication) and after discharge (late complication) were compared in groups. Plastic and orthopaedic surgeons performed cosmetic evaluations with the modified Vancouver Scar Scale (VSS) and Likert scale at three and six months postoperatively and compared in groups. RESULTS: A total of 249 arthroplasties (suture group=88 patients; staple group=94 patients; OCA-M group=67 patients) were included in the study. The OCA-M group had a significantly lower early complication rate than the suture group (p=0.015). For THA, the OCA-M group had a significantly lower total complication rate than the suture group (p=0.048). For TKA, there was no significant difference among the three groups. The complication rate in the OCA-M group showed no significant difference between THA/TKA. With regards to the VSS, the OCA-M group was significantly better for cosmetic qualities than the suture group (p=<0.001, p=0.021 at three and six months, respectively). For the Likert scale, the OCA-M group was also significantly better for cosmetic qualities than the suture group and staple group (suture-OCA-M, p=0.003 (three months), p=<0.001 (six months); staple-OCA-M, p=0.027 (three months)). CONCLUSION: In this study, the OCA-M complication rate was low compared to suturing and similar to stapling. Moreover, better cosmetic outcomes were achieved compared to suturing and stapling.


Assuntos
Artroplastia de Quadril , Artroplastia do Joelho , Cianoacrilatos , Humanos , Telas Cirúrgicas , Técnicas de Sutura , Suturas , Poliésteres/uso terapêutico
13.
J Nutr Sci Vitaminol (Tokyo) ; 70(1): 82-87, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38417856

RESUMO

We investigated the effects of short-term dietary zinc deficiency on zinc and calcium metabolism. Four-week-old male Wistar rats were divided into two pair-fed groups for a 1-wk treatment: zinc-deficient group (ZD, 1 ppm); control group (PF, 30 ppm). The mRNA expression of zinc transporters, such as Slc39a (Zip) 4, Zip5, Zip10, and Slc30a (ZnT) 1, in various tissues (liver, kidney, and duodenum) quickly responded to dietary zinc deficiency. Although there was no significant difference in serum calcium concentrations between the PF and ZD groups, serum 1,25-dihydroxycholecalciferol (1,25(OH)2D3) was higher in the ZD group than in the PF group. Moreover, short-term zinc deficiency significantly increased mRNA expression of transient receptor potential (TRP) cation channel subfamily vanilloid (V) member 6, S100 calcium binding protein G (S100g), and ATPase plasma membrane Ca2+ transporting 1 (Atp2b1) in the duodenum. Furthermore, short-term zinc deficiency increased vitamin D receptor (VDR) and cytochrome P450 family 24 subfamily A member 1 (Cyp24a1) mRNA expression in the kidney. These findings suggested that short-term zinc deficiency maintains serum calcium concentrations through Ca absorption-related gene expression in the duodenum, and that short-term zinc deficiency induced the expression of Cyp24a1 in kidney in response to an increase in the serum 1,25(OH)2D3 level.


Assuntos
Cálcio , Zinco , Ratos , Masculino , Animais , Cálcio/metabolismo , Vitamina D3 24-Hidroxilase/genética , Ratos Wistar , Dieta , Expressão Gênica , RNA Mensageiro/metabolismo
14.
Bioengineering (Basel) ; 11(2)2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38391666

RESUMO

Calcium phosphate-based synthetic bone is broadly used for the clinical treatment of bone defects caused by trauma and bone tumors. Synthetic bone is easy to use; however, its effects depend on the size and location of the bone defect. Many alternative treatment options are available, such as joint arthroplasty, autologous bone grafting, and allogeneic bone grafting. Although various biodegradable polymers are also being developed as synthetic bone material in scaffolds for regenerative medicine, the clinical application of commercial synthetic bone products with comparable performance to that of calcium phosphate bioceramics have yet to be realized. This review discusses the status quo of bone-regeneration therapy using artificial bone composed of calcium phosphate bioceramics such as ß-tricalcium phosphate (ßTCP), carbonate apatite, and hydroxyapatite (HA), in addition to the recent use of calcium phosphate bioceramics, biodegradable polymers, and their composites. New research has introduced potential materials such as octacalcium phosphate (OCP), biologically derived polymers, and synthetic biodegradable polymers. The performance of artificial bone is intricately related to conditions such as the intrinsic material, degradability, composite materials, manufacturing method, structure, and signaling molecules such as growth factors and cells. The development of new scaffold materials may offer more efficient bone regeneration.

15.
Int J Cardiol Heart Vasc ; 50: 101345, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38313451

RESUMO

Background: In patients with chronic heart failure (CHF), comorbidities are often managed with multiple medications, characterized by polypharmacy, leading to increased risk of potentially inappropriate medication and adverse effects. Methods: We studied 4,876 consecutive patients with CHF (Stage C/D, age 69.0 ± 12.3 years) in the CHART-2 study to evaluate the association among polypharmacy, underuse of HF medications, and all-cause death. Polypharmacy was defined as the daily use of ≥ 8 medications for the survival classification and regression tree analysis. Results: The average number of medications was 10 in the polypharmacy group and 5 in the non-polypharmacy group, respectively. Over a median of 8.3 (4.1-11.7) years, the incidence rate of all-cause death was significantly higher in the polypharmacy group (n = 2,108) than in the non-polypharmacy group (57.3 % vs. 40.6 %; adjusted hazard ratio [aHR] 1.34 (95 %CI, 1.22-1.48), P < 0.001), even in age < 55 years (26.6 % vs. 14.3 %; adjusted hazard ratio [aHR] 1.61 (95 %CI, 1.04-2.50), P = 0.033). In patients with polypharmacy, those without renin-angiotensin system inhibitors (RAS-I) and/or beta-blockers (N = 1,023) were associated with increased incidence of all-cause death as compared with those with both medications (aHR 1.18; 95 %CI 1.04-1.35, P = 0.012). Conclusions: Polypharmacy was associated with poor long-term prognosis, even in younger patients with CHF. Among 4,876 patients with CHF, 1023 (20.9%) with polypharmacy and underuse of RAS-I and/or beta-blocker were associated with increased risk of all-cause death.

16.
J Orthop Sci ; 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38233330

RESUMO

BACKGROUND: Restrictions in daily activities due to coronavirus infection countermeasures reduced opportunities for physical activity and social participation in people of all ages. This study investigated the associations of restricted outings on locomotive function during the COVID-19 pandemic using a cohort of middle-aged and elderly community-dwelling residents. METHODS: Registered citizens of 50-89 years old were targeted for this investigation. We established 8 groups based on age (50's, 60's, 70's, and 80's) and gender (male and female) after random sampling from the basic resident registry of Obuse town in 2014. All participants were surveyed by a 25-question geriatric locomotive function scale (GLFS-25) at the time of checkup before the COVID-19 pandemic. Then, in 2021 and 2022 after government restrictions on outings were lifted for COVID-19 pandemic, all participants were mailed questionnaires including the GLFS-25. A total of 296 (143 male and 153 female) participants who responded at least once were included. We evaluated the changes in opportunities to go out between pre- and post-pandemic time points and the impact on GLFS-25 scores. RESULTS: In total, 128 (43.2%) respondents had fewer opportunities to go out than the previous year. Pre- and post-pandemic GLFS-25 scores in the decreased outing (+) group were significantly worse than in the decreased outing (-) group (both p < 0.01). The final multivariate model revealed GLFS-25 score worsening beta coefficient of 0.27 for age (+10 years), 3.97 for male, 4.54 for decreased outings, and 4.46 for spinal canal stenosis. CONCLUSIONS: In this randomly sampled Japanese cohort based on a resident registry, restricted outings during the COVID-19 pandemic was a significant independent factor associated with lower locomotive function.

17.
Science ; 383(6678): 55-61, 2024 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-38175903

RESUMO

Decision-making is always coupled with some level of risk, with more pathological forms of risk-taking decisions manifesting as gambling disorders. In macaque monkeys trained in a high risk-high return (HH) versus low risk-low return (LL) choice task, we found that the reversible pharmacological inactivation of ventral Brodmann area 6 (area 6V) impaired the risk dependency of decision-making. Selective optogenetic activation of the mesofrontal pathway from the ventral tegmental area (VTA) to the ventral aspect of 6V resulted in stronger preference for HH, whereas activation of the pathway from the VTA to the dorsal aspect of 6V led to LL preference. Finally, computational decoding captured the modulations of behavioral preference. Our results suggest that VTA inputs to area 6V determine the decision balance between HH and LL.


Assuntos
Assunção de Riscos , Área Tegmentar Ventral , Animais , Área Tegmentar Ventral/citologia , Área Tegmentar Ventral/fisiologia , Macaca fuscata
18.
Spine (Phila Pa 1976) ; 49(8): 547-552, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-37014827

RESUMO

STUDY DESIGN: Retrospective cohort study with interrupted time series analysis. OBJECTIVE: To examine the clinical effectiveness of gelatin-thrombin matrix sealant (GTMS) on blood loss reduction after adolescent idiopathic scoliosis (AIS) surgery. SUMMARY OF BACKGROUND DATA: The real-world effectiveness of GTMS on blood loss reduction in AIS surgery has not been determined. PATIENTS AND METHODS: The medical records of patients receiving AIS surgery were retrospectively collected during a period before GTMS approval at our institution (January 22, 2010-January 21, 2015) as well as during a postintroduction period (January 22, 2015-January 22, 2020). The primary outcomes were intraoperative blood loss, drain output over 24 hours, and total blood loss (intraoperative blood loss + drain output over 24 h). Interrupted time series analysis using a segmented linear regression model was used to estimate the effect of GTMS on blood loss reduction. RESULTS: A total of 179 AIS patients [mean age (range): 15.4 (11-30) yr; 159 females and 20 males; 63 preintroduction patients and 116 postintroduction patients] were included. After its introduction, GTMS was used in 40% of cases. Interrupted time series analysis revealed changes of -340 mL (95% CI: -649 to -31, P = 0.03) for intraoperative blood loss, -35 mL (95% CI: -124 to 55, P = 0.44) for drain output over 24 hours, and -375 mL (95% CI: -698 to -51, P = 0.02) for total blood loss. CONCLUSIONS: The availability of GTMS was significantly associated with reduced intraoperative and total blood loss in AIS surgery. GTMS use as needed is recommended to control intraoperative bleeding in the setting of AIS surgery. LEVEL OF EVIDENCE: 3.


Assuntos
Cifose , Escoliose , Fusão Vertebral , Adolescente , Feminino , Humanos , Masculino , Perda Sanguínea Cirúrgica , Gelatina , Análise de Séries Temporais Interrompida , Estudos Retrospectivos , Escoliose/cirurgia , Trombina , Resultado do Tratamento , Criança , Adulto Jovem , Adulto
19.
Jpn J Infect Dis ; 77(2): 118-120, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38030269

RESUMO

Legionella pneumophila serogroup (SG) 1, the main cause of Legionnaires' disease, can be diagnosed using urinary antigen testing kits. However, lower respiratory tract specimen cultures are required to identify L. pneumophila SG 2-15. We attempted to detect L. pneumophila SG-specific genes in a culture-negative sputum specimen from a patient with pneumonia who was suspected to have Legionnaires' disease. Two multiplex PCR methods targeting L. pneumophila were modified and amplicons considered to be SG13 specific were detected. Direct sequencing revealed that the amplicons were identical to the nucleotide sequence of L. pneumophila SG13. Based on the presentation and clinical course (fever, muscle pain, disturbance of consciousness, high C-reactive protein titer, rhabdomyolysis, hypophosphatemia, and symptomatic improvement with levofloxacin treatment), in combination with the detection of L. pneumophila SG-specific genes, we suspected L. pneumophila SG13 pneumonia. L. pneumophila non-SG1 pneumonia is thought to be underestimated because of its difficult laboratory diagnosis. The modified multiplex PCR system for lower respiratory tract specimens revealed in this study is likely to improve the diagnosis of Legionnaires' disease caused by L. pneumophila SG13 and other SGs.


Assuntos
Legionella pneumophila , Doença dos Legionários , Pneumonia , Humanos , Legionella pneumophila/genética , Doença dos Legionários/diagnóstico , Doença dos Legionários/tratamento farmacológico , Sorogrupo , Escarro , Pneumonia/diagnóstico
20.
J Cardiol ; 83(1): 17-24, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37524299

RESUMO

Myocardial infarction with non-obstructive coronary arteries (MINOCA) is a heterogeneous and diverse disease entity, which accounts for about 6 % of all acute myocardial infarction (AMI) cases. In patients with chest pain and acute myocardial injury detected by a highly sensitive troponin assay, the absence of epicardial coronary stenosis of 50 % or greater on angiography leads to the working diagnosis of MINOCA. The updated JCS/CVIT/JCC 2023 Guideline described MINOCA as a new disease concept and recommended a multimodality approach to uncovering the underlying causes of MINOCA. Cardiac magnetic resonance (CMR) is useful in not only making a definite diagnosis of MINOCA, but also excluding non-ischemic causes that mimic AMI such as takotsubo cardiomyopathy and myocarditis. Meanwhile, intracoronary imaging, particularly optical coherence tomography (OCT), enables us to evaluate precisely intracoronary morphological alterations including plaque disruption and spontaneous coronary artery dissection which are not revealed by angiographic findings alone. Recent studies have shown that an initial workup with the combination of CMR and OCT could provide a definite diagnosis in a significant percentage of patients suspected of MINOCA. Consecutively, patients with inconclusive results of a series of CMR and OCT implementation are eligible for assessing the potential for coronary functional abnormalities or blood coagulopathy as another factor involved in the development of MINOCA. Although uncovering the pathogenesis of MINOCA might be essential for establishing an individualized treatment approach, significant knowledge gaps in terms of secondary prevention strategies for MINOCA focusing on the improvement of long-term prognosis remain to be overcome. In this review, we summarize our current understanding of MINOCA and highlight contemporary diagnostic approaches for patients with suspected MINOCA.


Assuntos
Doença da Artéria Coronariana , Infarto do Miocárdio , Placa Aterosclerótica , Humanos , Vasos Coronários/patologia , MINOCA , Angiografia Coronária/efeitos adversos , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/patologia , Placa Aterosclerótica/patologia , Doença da Artéria Coronariana/complicações
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