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The purpose of this study is to illustrate how matching approaches based on different balancing scores lead to variations in the treatment effect estimators. We introduced a case study evaluating the effect of anti-thrombotic agents on the severe progression of patients with intracerebral hemorrhage. We extracted subpopulations based on propensity and prognostic scores and then estimated the relative risk between the treatment groups. Furthermore, to illustrate the situation where the treatment effect estimates varied depending on employed balancing scores, we conducted a simulation experiment. In the case study, the matching using different balancing scores extracted subpopulations with different characteristics. Then, the estimated relative risk (95% confidence interval) was 1.27 (0.98–1.94) among the propensity score matched cohort, whereas it was 0.91 (0.76–1.08) among the prognostic score matched cohort. In the simulation experiments, the results indicated that the matching schemes based on different balancing scores created distinct matched cohorts, leading to varying estimates under treatment effect heterogeneity. Moreover, the variability of the estimated effect becomes substantial when there are covariates strongly related to the dependent variable of the nuisance functions. The difference in the selected subpopulation via matching based on different balancing scores is a thoughtful factor that can result in different estimates when there is effect heterogeneity. In practice, we recommend assessing the characteristics of the matched subpopulation and employing the balancing score that can estimate the treatment effect among the target population of interest in each study. Plain Language Summary: This study aimed to understand why different methods of matching patients in a study can lead to different estimates of how well a treatment works. We used a real example of a study where the treatment's effectiveness varied for different patients and compared how different methods of matching patients affected the results. We also did a series of experiments to see how the different methods affected estimates of treatment effect when the effectiveness varied among patients. Our study found that the different matching methods extracted the different patients. The difference in the matched patients led to very different results, especially when the treatment's effectiveness was not the same for all patients. Therefore, it is important to check the characteristics of patients after matching and consider whether the treatment's effectiveness is not the same for all patients. [ABSTRACT FROM AUTHOR]

The association between cancer survivors and stroke deaths remains unclear. We aimed to evaluate the risk of fatal stroke in patients with cancer. This study was conducted using data from the Osaka Cancer Registry and vital statistics in Japan, collected from 1985 to 2013. We extracted patient data and investigated the causes of death. Standardized mortality ratios were calculated to compare the risk of stroke in patients with cancer to that in the general population. Poisson regression models were used to estimate the risk of stroke in patients with cancer and other cancer subgroups. Stroke types were used for risk stratification. We identified 688,473 eligible patients with cancer. The cohort contributed 2,668,126 person-years at risk. During the study period, 337,117 patients died; stroke was the cause of death in 5496 patients. Stroke types included cerebral infarction (3259), intracerebral hemorrhage (1539), subarachnoid hemorrhage (364), and other cerebrovascular diseases (334). The crude mortality rate from fatal stroke was 205.99 per 100,000 person-years. The standardized mortality ratio (95 % confidence interval) for fatal stroke was 1.75 (1.71–1.80). When stratified by stroke types, the ratios for cerebral infarction, intracerebral hemorrhage, and subarachnoid hemorrhage were 1.83 (1.76–1.89), 2.38 (2.26–2.50), and 2.28 (2.03–2.56), respectively. The risk of fatal stroke increased with time after cancer diagnosis. The multivariate Poisson regression model indicated that men were more likely to die of stroke than women. Cancer survivors have a higher risk of fatal stroke than the general population across all stroke types. [Display omitted] • The risk of fatal stroke in cancer survivors remains unclear. • Cancer survivors have a significant high risk of death from stroke. • The risks varied by cerebral infarction, intracerebral hemorrhage, and subarachnoid hemorrhage. • Careful follow-up for cancer survivors in clinical practice is required. • The risk of fatal stroke among cancer survivors has decreased in recent years. [ABSTRACT FROM AUTHOR]

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The risk of Parkinson's disease (PD)-related death in patients with cancer largely unexplored. We analyzed data from the Neoplasms ANd other causes of DEath (NANDE) study, which investigates the causes of death in patients with cancer in Japan. Standardized mortality ratios (SMRs) were calculated to compare the risk of PD-related deaths in patients with cancer to that of the general population. Poisson regression models were employed to estimate the relative risk of PD-related death in the subgroups. The cohort included 548,485 patients with cancer, yielding 2,047,398 person-years at risk from 1995 to 2013. During the study period, 242,250 patients died and 145 deaths were attributable to PD. The SMR for PD-related death was 2.34 (95% confidence interval [CI]: 1.99–2.75). Patients who were diagnosed with cancer before 70 years of age had a high SMR (>5) for PD-related deaths. The SMR of patients with mouth-to-stomach cancers (lip, oral cavity, pharynx, esophagus, and stomach cancers) was 3.72 (95% CI: 2.84–4.86), while that of those with other cancers was 1.93 (95% CI: 1.57–2.37). The multivariate Poisson regression model revealed that patients with mouth-to-stomach cancers were more likely to die of PD than those without (relative risk 2.07, 95 % CI; 1.46–2.93). Patients with cancer are at a high risk of PD-related death; particularly, mouth-to-stomach cancers and potentially obstructing medication for PD are attributable to a high mortality risk. Careful management, including adequate PD treatment, would benefit cancer survivors with PD and reduce the risk of PD-related death. • Cancer patients have an increased risk of death from Parkinson's disease (PD). • PD-related deaths were twice as high for mouth-to-stomach cancers than for others. • Clinicians should recognize high risk of PD-related death in cancer patients. [ABSTRACT FROM AUTHOR]

The incidence of cancer-associated stroke has increased with the prolonged survival times of cancer patients. Recent genetic studies have led to progress in cancer therapeutics, but relationships between oncogenic mutations and stroke remain elusive. Here, we focused on the driver gene KRAS , which is the predominant RAS isoform mutated in multiple cancer types, in cancer associated stroke study. KRAS G13D /− and parental human colorectal carcinoma HCT116 cells were inoculated into mice that were then subjected to a photochemically-induced thrombosis model to establish ischemic stroke. We found that cancer inoculation exacerbated neurological deficits after stroke. Moreover, mice inoculated with KRAS G13D /− cells showed worse neurological deficits after stroke compared with mice inoculated with parental cells. Stroke promoted tumor growth, and the KRAS G13D /− allele enhanced this growth. Brain RNA sequencing analysis and serum ELISA showed that chemokines and cytokines mediating pro-inflammatory responses were upregulated in mice inoculated with KRAS G13D /− cells compared with those inoculated with parental cells. STAT3 phosphorylation was promoted following ischemic stroke in the KRAS G13D /− group compared with in the parental group, and STAT3 inhibition significantly ameliorated stroke outcomes by mitigating microglia/macrophage polarization. Finally, we compared the prognosis and mortality of colorectal cancer patients with or without stroke onset between 1 January 2007 and 31 December 2020 using a hospital-based cancer registry and found that colorectal cancer patients with stroke onset within 3 months after cancer diagnosis had a worse prognosis. Our work suggests an interplay between KRAS and ischemic stroke that may offer insight into future treatments for cancer-associated stroke. • Colorectal cancer and stroke interact mutually and aggravated each other. • KRAS G13D -mutant colorectal cancer triggered STAT3 activation in the brain that promoted post-stroke neuroinflammation. • STAT3 inhibition attenuated stroke outcomes by suppressing neuroinflammation and attenuating p44/42 MAPK pathway inhibition after stroke. [ABSTRACT FROM AUTHOR]

Objective To clarify the characteristics of cryptogenic stroke in patients with active cancer. Methods Patients with or without cancer diagnosed with acute ischemic stroke between January 2006 and February 2015 were extracted from a prospectively collected stroke database of Osaka University Hospital. Patients were categorized according to the presence of active cancer and known stroke mechanisms. Results Among 1191 patients with acute ischemic stroke, 145 (12%) had active cancer. Patients with active cancer were diagnosed more often with cryptogenic stroke than were patients without cancer (47% vs. 12%, P < 0.001). Compared with cryptogenic stroke patients without cancer, cryptogenic stroke patients with active cancer had fewer atherosclerotic risk factors, lower nutrition status, higher plasma D-dimer levels, and multiple vascular lesions. In a multivariate logistic analysis, plasma D-dimer level (odds ratio [OR] per 1 standard deviation increase: 6.30; 95% confidence interval [CI]: 2.94-15.69; P < 0.001), and the presence of multiple vascular lesions (OR: 6.40; 95% CI: 2.35-18.35; P < 0.001) were independent predictors of active cancer. When comparing active cancer patients who had known stroke mechanisms with those who had cryptogenic stroke, high plasma D-dimer levels, multiple vascular lesions, and receiving chemotherapy and/or radiation therapy were associated with cryptogenic stroke etiology. Interpretation In cryptogenic stroke, patients with active cancer has a unique pathology characterized by high plasma D-dimer levels and multiple vascular lesions. The hypercoagulable state and malnutrition due to cancer and its treatments potentially influence the development of cryptogenic stroke in cancer patients. [ABSTRACT FROM AUTHOR]

Direct oral anticoagulants (DOACs) are at least as efficacious as conventional anticoagulation therapy for the initial and long-term treatment of cancer patients with venous thromboembolism (VTE). Whether DOACs are non-inferior to low-molecular-weight heparin for the management of cancer patients with VTE is under investigation. In addition, the efficacy of DOACs for the treatment of cancer patients with arterial thrombosis (e.g., ischemic stroke) remains unclear. Herein, we report on two cancer patients admitted to our hospital with Stage IV gastric adenocarcinoma who were being treated with DOACs due to a history of VTE and had developed their first ever ischemic stroke, which was diagnosed due to cancer-related hypercoagulation. Notably, neither patient had recurrence of VTE during the course of their disease. In cancer-related thrombosis, DOACs effectively reduce VTE, but may be insufficient for preventing ischemic stroke. [ABSTRACT FROM AUTHOR]

Stroke is occasionally the first manifestation of occult infective endocarditids. Although infective endocarditids commonly presents acutely, infective endocarditids remains a diagnostic challenge in a patient with few symptoms or culture-negative endocarditis. Here, we present a 74-year-old Japanese woman with recurrent ischemic stroke and palmoplantar pustulosis caused by occult postoperative infective endocarditids. She had undergone an operation for mitral regurgitation, mitral annuloplasty, 4 years before admission. Intriguingly, our patient suffered from intractable palmoplantar pustulosis after cardiac surgery, but the patient's cutaneous manifestations completely resolved after treatment of occult postoperative infective endocarditids. In patients with unexplained intermittent fever and palmoplantar pustulosis after cardiac surgery, clinicians need to consider the possibility of occult postoperative infective endocarditids. [ABSTRACT FROM AUTHOR]

The article discusses a study on the accuracy of diagnostic codes for stroke in a hospital-based cancer registry using electronic medical records (EMRs) in Japan. The study involved 27,932 patients enrolled in the hospital-based cancer registry at Osaka University Hospital. It analyzed the details of the diagnostic codes, including acute or old diagnoses and primary or other diagnoses.

'Yips' in golf is a complex spectrum of anxiety and movement-disorder that affects competitive sporting performance. With unclear etiology and high prevalence documented in western literature, the perception and management of this psycho-neuromuscular problem among Japanese elite golfers is unknown. The objective of this study was to explore factors associated with yips, investigate the performance deficits and the strategies implemented to prevent yips. We surveyed approx. 1300 professional golfers on their golfing habits, anxiety and musculoskeletal problems, kinematic deficits, changes in training and their outcomes. Statistical procedures included multiple logistic regression and network analysis. 35% of the respondents had experienced yips in their career, their odds increasing proportionally to their golfing experience. Regardless of musculoskeletal symptoms, about 57% of all yips-golfers attributed their symptoms to psychological causes. Network analysis highlighted characteristic movement patterns, i.e. slowing, forceful or freezing of movement for putting, approach and teeing shots respectively. Golfers' self-administered strategies to relieve yips were mostly inconsequential. Within the limits of our self-reported survey, most golfers perceived yips as a psychological phenomenon despite evidence pointing to a movement-disorder. While self-administered interventions were satisfactory at best, it may be imperative to sensitize golfers from a movement-disorder standpoint for early management of the problem. [ABSTRACT FROM AUTHOR]

Objectives: Several studies have investigated that anticholinergic drugs cause cognitive impairment. However, the risk of dementia associated with anticholinergics has not been extensively investigated in the super‐aging society of Japan. We conducted this study to assess the association between anticholinergic drugs and the risk of dementia in older adults in Japan. Methods: This nested case‐control study used data from the Longevity Improvement & Fair Evidence Study, which includes claim data in Japan from 2014 to 2020. We included 66,478 cases of diagnosed dementia and 328,919 matched controls aged ≥65 years, matched by age, sex, municipality, and cohort entry year. Primary exposure was the total cumulative anticholinergic drugs prescribed from cohort entry date to event date or matched index date, which was the total standardized daily doses for each patient, calculated by adding the total dose of different types of anticholinergic drugs in each prescription, divided by the World Health Organization‐defined daily dose values. Odds ratios for dementia associated with cumulative exposure to anticholinergic drugs were calculated using conditional logistic regression adjusted for confounding variables. Results: The mean (standard deviation) age at index date was 84.3 (6.9), and the percentage of women was 62.1%. From cohort entry date to event date or matched index date, 18.8% of the case patients and 13.7% of the controls were prescribed at least one anticholinergic drug. In the multivariable‐adjusted model, individuals with anticholinergic drugs prescribed had significantly higher odds of being diagnosed with dementia (adjusted odds ratio, 1.50 [95% confidence interval, 1.47–1.54]). Among specific types of anticholinergic drugs, a significant increase in risk was observed with the use of antidepressants, antiparkinsonian drugs, antipsychotics, and bladder antimuscarinics in a fully multivariable‐adjusted model. Conclusions: Several types of anticholinergic drugs used by older adults in Japan are associated with an increased risk of dementia. These findings suggest that the underlying risks should be considered alongside the benefits of prescribing anticholinergic drugs to this population. Key points: The risk of dementia associated with anticholinergics has not been extensively investigated in the super‐aging society of Japan.This nested case‐control study found a statistically significant association between anticholinergic drug use and the risk of dementia, especially for antipsychotics, antiparkinsonian agents, antidepressants, and bladder antimuscarinics, after adjusting for confounding variables.The prescription of specific types of anticholinergic drugs to older adults should be made with caution due to the associated risk of dementia. [ABSTRACT FROM AUTHOR]

Blood–brain barrier (BBB) disruption contributes to brain injury and neurological impairment. Tight junctions (TJs) and cell–cell adhesion complexes develop between endothelial cells in the brain to establish and maintain the BBB. Occludin, the first transmembrane protein identified in TJs, has received intense research interest because numerous in vitro studies have suggested its importance in maintaining BBB integrity. However, its role in maintaining BBB integrity after ischemic stroke is less clear owing to the lack of in vivo evidence. This study aimed to investigate the dynamics and function of occludin across the acute and chronic phases after stroke using occludin-deficient mice. By photochemically induced thrombosis model, the expression of occludin was decreased in brain endothelial cells from ischemic lesions. The neurological function of occludin-deficient mice was continuously impaired compared to that of wild-type mice. BBB integrity evaluated by Evans blue and 0.5-kDa fluorescein in the acute phase and by 10-kDa fluorescein isothiocyanate-labeled dextran in the chronic phase was decreased to a greater extent after stroke in occludin-deficient mice. Furthermore, occludin-deficient mice showed decreased claudin-5 and neovascularization after stroke. Our study reveals that occludin plays an important role from the acute to the chronic phase after ischemic stroke in vivo. [ABSTRACT FROM AUTHOR]

The potential impact of long-term left ventricular assist device (LVAD) support on the brain remains unclear. This study aimed to investigate cerebral microvascular damage in patients after long-term LVAD implantation using magnetic resonance imaging (MRI). We reviewed the medical records of patients after continuous-flow LVAD implantation in our hospital from 2006 to 2016, who underwent brain MRI after LVAD explantation for either transplantation or recovery. Age- and sex-matched healthy controls and patients with chronic heart failure (CHF) were collected from our pooled MRI database. The presence of cerebral microbleeds (CMBs) and cortical superficial siderosis and the severity of white matter hyperintensity (WMH) and cerebral atrophy were compared between patients with prior LVAD and 2 control groups. This study included 49 patients with prior LVAD, 49 healthy controls, and 45 patients with CHF. CMBs and cortical superficial siderosis were detected in 98% (p < 0.001) and 31% (p < 0.001) of patients with prior LVAD, respectively. The number of CMBs was higher in patients with prior LVAD than in the 2 control groups. The severity of the WMH was higher in patients with prior LVAD than in healthy controls but similar to that in patients with CHF. Quantitative analyses of cerebral atrophy revealed a significantly higher bicaudate ratio and cella media index in patients with prior LVAD than in the 2 control groups. Patients after long-term LVAD support showed a higher prevalence of CMBs and cortical superficial siderosis and more severe cerebral atrophy than did controls. These findings may indicate cerebral microvascular damages in long-term LVAD support patients. [ABSTRACT FROM AUTHOR]

Background The temporal and anatomical features of vasoconstriction in patients with reversible cerebral vasoconstriction syndrome within hours after symptom onset, in the hyperacute phase, are unclear. Case result Herein we report the cases of two patients with acute severe headache who were diagnosed with reversible cerebral vasoconstriction syndrome. Magnetic resonance imaging within hours after symptom onset revealed multiple areas of isolated cortical vasogenic edema and hyperintense vessel signs of the distal cerebral arteries. Follow-up imaging performed four days later in both cases showed diffuse segmental arterial vasoconstriction in the proximal regions of the cerebral arteries. Both patients received antivasoconstrictive therapy shortly after admission, and neither had neurological sequelae at discharge. The magnetic resonance imaging findings improved gradually within three months after symptom onset. Conclusion Isolated cortical vasogenic edema and hyperintense vessel signs, when observed within hours from sudden severe headache onset, may be useful early markers of reversible cerebral vasoconstriction syndrome. [ABSTRACT FROM AUTHOR]

Background: This study aimed to validate an algorithm that determines stroke diagnostic code accuracy, in a hospital-based cancer registry, using electronic medical records (EMRs) in Japan.Methods: The subjects were 27,932 patients enrolled in the hospital-based cancer registry of Osaka University Hospital, between January 1, 2007 and December 31, 2015. The ICD-10 (international classification of diseases, 10th revision) diagnostic codes for stroke were extracted from the EMR database. Specifically, subarachnoid hemorrhage (I60); intracerebral hemorrhage (I61); cerebral infarction (I63); and other transient cerebral ischemic attacks and related syndromes and transient cerebral ischemic attack (unspecified) (G458 and G459), respectively. Diagnostic codes, both "definite" and "suspected," and brain imaging information were extracted from the database. We set the algorithm with the combination of the diagnostic code and/or the brain imaging information, and manually reviewed the presence or absence of the acute cerebrovascular disease with medical charts.Results: A total of 2654 diagnostic codes, 1991 "definite" and 663 "suspected," were identified. After excluding duplicates, the numbers of "definite" and "suspected" diagnostic codes were 912 and 228, respectively. The proportion of the presence of the disease in the "definite" diagnostic code was 22%; this raised 51% with the combination of the diagnostic code and the use of brain imaging information. When adding the interval of when brain imaging was performed (within 30 days and within 1 day) to the diagnostic code, the proportion increased to 84% and 90%, respectively. In the algorithm of "definite" diagnostic code, history of stroke was the most common in the diagnostic code, but in the algorithm of "definite" diagnostic code and the use of brain imaging within 1 day, stroke mimics was the most frequent.Conclusions: Combining the diagnostic code and clinical examination improved the proportion of the presence of disease in the diagnostic code and achieved appropriate accuracy for research. Clinical research using EMRs require outcome validation prior to conducting a study. [ABSTRACT FROM AUTHOR]