Pro-Hemorrhagic Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy Associated with NOTCH3 p.R75P Mutation with Low Vascular NOTCH3 Aggregation Property.

OBJECTIVES: Intracerebral hemorrhage (ICH) and cerebral microbleeds (CMB) in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy are more common in East Asian populations than in people of white European ancestry. We hypothesized that the ethnic difference is explained by the East Asian-specific NOTCH3 p.R75P mutation. METHODS: This retrospective observational study included 118 patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy in Japanese and Korean cohorts. We investigated whether the p.R75P mutation is associated with symptomatic ICH and multiple CMB (>5) using quasi-Poisson regression models. We predicted the NOTCH3 extracellular domain protein structures in silico and graded NOTCH3 extracellular domain immunostaining in skin vessels of some patients, with subsequent comparisons between p.R75P and other conventional mutations. RESULTS: Among 63 Japanese patients (median age 55 years; 56% men), 15 had a p.R75P mutation, significantly associated with symptomatic ICH (adjusted relative risk 9.56, 95% CI 2.45-37.31), multiple CMB (3.00, 1.34-6.71), and absence of temporopolar lesions (4.91, 2.29-10.52) after adjustment for age, sex, hypertension, and antithrombotics. In the Korean cohort (n = 55; median age 55 years; 51% men), the p.R75P mutation (n = 13) was also associated with symptomatic ICH (8.11, 1.83-35.89), multiple CMB (1.90, 1.01-3.56), and absence of temporopolar lesions (2.32, 1.08-4.97). Structural analysis revealed solvent-exposed free cysteine thiols in conventional mutations, directly causing aggregation, whereas a stereochemically incompatible proline residue structure in p.R75P lowers correct disulfide bond formation probability, indirectly causing aggregation. Pathologically, the p.R75P mutation resulted in less vascular NOTCH3 extracellular domain accumulation than the other conventional mutations. INTERPRETATION: NOTCH3 p.R75P mutation is associated with hemorrhagic presentations, milder temporopolar lesions, and distinct mutant protein structure properties. ANN NEUROL 2024;95:1040-1054.

A Novel Method to Localize Patency Capsule by Ileocolonoscopy Facilitates Endoscopic Assessment of the Small and Large Intestine in Patients with Crohn's Disease.

INTRODUCTION: Patients with Crohn's disease (CD) require an assessment of small bowel lesions, while difficulties exist in performing small intestinal examinations, especially in small-sized medical offices. Small bowel capsule endoscopy (SBCE) is handy and can be performed in most clinical settings. The only drawback of SBCE is a requirement of patency testing prior to the exam because it sometimes requires CT scanning to localize the ingested patency capsule (PC), which may be a substantial burden for the patient. We have developed a novel PC detection system named PICS (patency capsule, ileocolonoscopy, and small bowel capsule endoscopy) method by which we can avoid CT scanning. In the PICS method, ileocolonoscopy (ICS) is performed after 30-33 h of PC ingestion and the PC can be localized by ICS in patients who have not excreted the PC, and the entire intestine can be examined in combination with subsequent SBCE without additional bowel preparation. The aim of this study was to assess the usefulness and safety of the PICS method for CD patients. METHODS: CD patients who underwent PICS method from April 2021 to March 2023 were reviewed for clinical data, outcome of PICS method including the rates of PC detection by ICS, the number of patients underwent SBCE, and adverse events. Lewis score was used to assess SBCE results. RESULTS: The PICS method was performed in 54 patients. The median age of patients was 28.5 years old, and 64.8% of them were ileocolic type. The median disease duration was 10.5 months and 24.1% had history of small bowel resection. Five cases (9.3%) confirmed gastrointestinal patency by ICS, and none of the cases required CT scanning. One patient who could not be confirmed patency by ICS, and the other patient who excreted PC but was found ileal stenosis by ICS did not undergo SBCE. Remaining 52 patients received SBCE, and the median Lewis score of them was 0 (IQR 0, 450). There were no adverse events including small bowel obstruction by PC and SBCE retention in this series. CONCLUSION: The PICS method is not only feasible and safe but also convenient to assess disease extent in patients with CD. By localizing PC with ICS, additional CT scanning could be unnecessary for SBCE, which benefits both physicians and CD patients.

Long-term results following off-pump coronary-artery bypass grafting in left ventricular dysfunction.

Severe left ventricular (LV) dysfunction is an independent risk factor for early and long-term mortality after coronary-artery bypass grafting (CABG). Off-pump CABG (OPCAB) significantly reduces the early incidence of major complications in high-risk patients. Moreover, bilateral internal thoracic artery (BITA) grafting after CABG is associated with improved long-term outcomes. We aimed to evaluate the impact of multivessel OPCAB with BITA grafting for complete revascularization on postoperative and long-term outcomes in patients with low LV ejection fraction (EF). We included 121 patients with EF ≤ 30.0% who underwent isolated multivessel OPCAB (average LVEF, 24.8%) between April 2007 and December 2019. Sixty-six patients received BITA grafts, while 55 had single internal thoracic artery (SITA) grafts. We conducted multivariate analyses to examine the correlation between perioperative data and late mortality rate. The early mortality rate was 1.65%. After excluding in-hospital mortality cases, we performed long-term follow-up of 119 patients. Early postoperative echocardiography showed significant LVEF improvement in 89 (75.2%) patients. However, LVEF remained ≤ 30.0% in 30 (24.8%) patients. We recorded 15 and 30 cases of cardiac death and cardiac events, respectively, during the long-term follow-up period. Postoperative LVEF ≤ 30.0% (P < 0.01) and no use of BITA grafting (P = 0.03) were significant predictors of cardiac death and events; moreover, hemodialysis was a significant predictor of all-cause mortality rather than cardiac death. Multivessel OPCAB in patients with severe LV dysfunction was associated with acceptable in-hospital mortality and early postoperative improvement in LV function. Additionally, OPCAB with BITA grafting may provide long-term benefits with respect to cardiac death and events. However, the long-term benefits were significantly limited in patients without early postoperative improvement in LV function and patients with chronic hemodialysis.Clinical registration number: 5590 (14/5/2020 Tokyo Women's Medical University).

Propensity score-matched comparison of total arterial off- and on-pump coronary artery bypass with complete revascularization.

Little is known regarding the long-term (> 10 years) outcomes and risk factors of total arterial coronary artery bypass grafting (CABG). This study evaluated the long-term outcomes and risk factors for all-cause mortality and major adverse cardiac and cerebrovascular events (MACCEs) following total arterial on-pump CABG (ONCAB) or off-pump CABG (OPCAB) with complete revascularization. This retrospective cohort analysis enrolled patients with stable angina who underwent total arterial CABG with complete revascularization in our institute between July 2000 and June 2019. The endpoints were all-cause mortality and MACCE incidence, including a comparison between OPCAB and ONCAB. Long-term (10-year) outcomes were analyzed using propensity score-matched pairs, and risk factors were evaluated using univariate and multivariate analyses. Overall, 401 patients who underwent primary total arterial CABG were classified into the OPCAB (n = 269) and ONCAB (n = 132) groups. Using propensity score matching (PSM), 88 patients who underwent OPCAB were matched with 88 patients who underwent ONCAB. The mean follow-up period was 7.9 ± 6.3 years. No significant difference in all-cause mortality (hazard ratio, 1.04; 95% confidence interval, 0.53-2.04; p = 0.9138) and MACCE incidence (hazard ratio, 1.06; 95% confidence interval, 0.68-1.65; p = 0.7901) was observed between the two groups. Renal failure requiring dialysis was a significant risk factor for mortality (p < 0.0001) and MACCEs (p = 0.0003). Long-term outcomes of total arterial OPCAB and ONCAB with complete revascularization showed similar findings using PSM. Renal failure requiring dialysis was a significant risk factor for mortality and morbidity.Journal standard instruction requires an unstructured abstract; hence the headings provided in abstract were deleted. Kindly check and confirm.Thank you for your kindness.Clinical registration number 5598, Tokyo Women's Medical University Hospital.

Thirty-year outcomes of low-intensity anticoagulation for mechanical aortic valve.

The long-term safety, efficacy, and outcomes of low-intensity anticoagulation for mechanical heart valves remain unclear. This study aimed to evaluate the long-term outcomes of low-intensity anticoagulation therapy after aortic valve replacement (AVR) with a mechanical prosthesis. This retrospective cohort study consulted medical records and conducted a questionnaire to investigate 519 patients who underwent single AVR with the St. Jude Medical bileaflet valve and were in sinus rhythm. All patients were followed up with an international normalized ratio (INR) target of 1.6-2.5, and their INR values were checked throughout the follow-up period. The survival rate, incidence of major adverse cardiac and cerebrovascular events (MACCE), and risk factors for cardiac death and MACCE were investigated. The total follow-up was 9793 patient-years, and the follow-up periods were 19.9 (standard deviation [SD]: 7.9) years. The mean INR was 2.03 (SD: 0.54). Survival rates from cardiac death were 93.6% in 20 years and 85.2% in 30 years. Advanced age ≥ 70 years was the only significant risk factor for cardiac death and MACCE, and the INR < 2.0 was not significant risk factor for MACCE including thromboembolism or bleeding events. Low-intensity anticoagulation with an INR of 1.6-2.5 for patients with sinus rhythm after AVR with a bileaflet mechanical valve is safe and effective, even over 30 years.

Harboring Cnm-expressing Streptococcus mutans in the oral cavity relates to both deep and lobar cerebral microbleeds.

BACKGROUND: Cerebral microbleeds (CMBs) influence long-term prognoses of stroke patients. Streptococcus mutans expressing the collagen-binding protein Cnm induces cerebrovascular inflammation, impairing blood brain barrier integrity and causing cerebral bleeding. Here, we examine the association of Cnm-positive S. mutans with CMBs. METHODS: Acute stroke patients were selected from a single-center registry database. Oral carriage of Cnm-positive or Cnm-negative S. mutans was determined using polymerase chain reaction assays. The associations of Cnm-positive S. mutans with CMB number and specifically the presence of >10 CMBs were examined using quasi-Poisson and logistic regression models, respectively. RESULTS: This study included 3154 stroke patients, of which 428 patients (median [interquartile range] age, 73.0 [63.0-81.0] years; 269 men [62.9%]) underwent oral bacterial examinations. In total, 326 patients harbored S. mutans. After excluding four patients without imaging data, we compared patients with Cnm-positive (n = 72) and Cnm-negative (n = 250) S. mutans. Harboring Cnm-positive S. mutans was independently associated with the presence of >10 CMBs (adjusted odds ratio 2.20 [1.18-4.10]) and higher numbers of deep and lobar CMBs (adjusted risk ratio 1.61 [1.14-2.27] for deep; 5.14 [2.78-9.51] for lobar), but not infratentorial CMBs, after adjusting for age, sex, hypertension, stroke type, National Institutes of Health Stroke Scale score, and cerebral amyloid angiopathy. CONCLUSIONS: Harboring Cnm-positive S. mutans was independently associated with a higher number of CMBs in deep and lobar locations. Reducing Cnm-positive S. mutans in the oral cavity may serve as a novel therapeutic approach for stroke.

[Commando Procedure for Rapidly Progressing Infective Endocarditis in Immunosuppressive State: Report of a Case].

A 68-year-old woman with immunosuppressive state following chemotherapy for cancer of unknown primary origin developed infective endocarditis due to methicillin-resistant Staphylococcus aureus (MRSA). Echocardiography showed shunt blood flow from the aortic annular abscess into the left atrium, which indicated infection of the intervalvular fibrosa (IVF). She underwent Commando procedure owing to progression of heart failure. The aortic valve, IVF, and anterior leaflet of the mitral valve were resected. The mitral valve was replaced with a bioprosthesis, and a bovine pericardial patch was used to reconstruct the IVF and left atrial roof. Bentall procedure was performed because the infection extended to the sinus of Valsalva, and the ascending aorta was 49 mm in diameter. She had no serious postoperative complications and is currently being followed up at the outpatient clinic. Because infection in these patients are potentially fatal, we believe Commando procedure is effective in spite of high early mortality rate.

Pleiotropic neuroprotective effects of taxifolin in cerebral amyloid angiopathy.

Cerebral amyloid angiopathy (CAA) results from amyloid-ß deposition in the cerebrovasculature. It is frequently accompanied by Alzheimer's disease and causes dementia. We recently demonstrated that in a mouse model of CAA, taxifolin improved cerebral blood flow, promoted amyloid-ß removal from the brain, and prevented cognitive dysfunction when administered orally. Here we showed that taxifolin inhibited the intracerebral production of amyloid-ß through suppressing the ApoE-ERK1/2-amyloid-ß precursor protein axis, despite the low permeability of the blood-brain barrier to taxifolin. Higher expression levels of triggering receptor expressed on myeloid cell 2 (TREM2) were associated with the exacerbation of inflammation in the brain. Taxifolin suppressed inflammation, alleviating the accumulation of TREM2-expressing cells in the brain. It also mitigated glutamate levels and oxidative tissue damage and reduced brain levels of active caspases, indicative of apoptotic cell death. Thus, the oral administration of taxifolin had intracerebral pleiotropic neuroprotective effects on CAA through suppressing amyloid-ß production and beneficially modulating proinflammatory microglial phenotypes.

Amyloid-ß: Structure, Function, and Pathophysiological Significance in Neurodegenerative Diseases.

The rate of dementia continues to increase worldwide; however, there currently exist no therapeutic strategies for this condition [...].

[Resection of Left Upper Division by Uniportal Video-assisted Thoracoscopic Surgery for Congenital Bronchial Atresia:Report of a Case].

We report a case of congenital bronchial atresia resected by the uniportal thoracoscopic approach. A man in his 20s with congenital bronchial atresia diagnosed at 16 years of age visited our hospital with gradually worsening shortness of breath. Chest computed tomography revealed a localized emphysematous area that progressively increased in size, in the left upper lobe and the absence of a left upper division bronchus with mucoid impaction. Surgical treatment was deemed necessary in view of dyspnea and progressively worsening emphysema, and the resection of left upper division was performed by uniportal video-assisted thoracoscopic surgery.

[Introduction and Activities of Nurse Practitioner in Japan in a University Hospital].

Nurse practitioner (NP) is widely known to be an essential position of medical team in the United States, but has not yet been established as an official qualification in Japan. NP in Japan (NP-J) is accepted instead of NP, but they are not the same. We summarized the actual activities of NP-J at our hospital and had an insight into the roles of NP-J in a university hospital and the problems of introduction of NP in the future. The benefits of working as a NP-J at a university hospital are the safe acquisition of procedures at an educational institution and the involvement of various departments. In the future, the education of NP-J in a university hospital may lead to the training of NP-J working in public and private hospitals. The problem of introduction of NP in the future is the legislation. The importance of task shifting and education of NP-J in a university hospital may lead to the spread of NP in the future in Japan.

[A case of advanced pancreatic cancer with spontaneous tumor lysis syndrome].

A 74-year-old male with pancreatic cancer and multiple huge liver metastases received palliative care due to the cancer progression after chemotherapy. The patient was admitted to our hospital for increased abdominal pain and dehydration. Tumor lysis syndrome was diagnosed on the fifth hospital day owing to the advancement of renal impairment, hyperuricemia, hyperkalemia, and hyperphosphatemia. The patient's condition rapidly deteriorated despite increased intravenous infusion and the provision of antihyperuricemia medicine and demised on the seventh hospital day. Autopsy results revealed generalized necrosis of the tumor, consistent with tumor lysis syndrome.

Technical Features and Clinical Outcomes of Coronary Venous Left Ventricular Lead Removal and Reimplantation.

BACKGROUND: The number of patients undergoing cardiac resynchronization therapy has increased. Consequently, there is increased frequency in the removal and reimplantation of coronary venous (CV) leads due to infection or malfunction.Methods and Results:A total of 345 consecutive patients referred for lead(s) extraction were reviewed. Of these, 34 patients who underwent a CV lead removal were investigated. The indications for CV leads removal were device-related infections in 29 patients and lead malfunctions in 5 patients. The average duration of the CV leads was 4.1±3.8 years. All CV leads were successfully removed without any major complications, except for 1 in-hospital death. Successful CV lead removal by simple traction (ST) was achieved in 21 patients (62%), whereas extraction tools were required in 13 patients (38%). Local infection and CV lead dwell time were significantly associated with successful ST (P=0.04 and P=0.014, respectively). CV lead re-implantation was successfully performed in 25 patients; however, a right-side approach was required in 92%, and occlusion/stenosis of the previous CV was observed in 80% of the patients. CONCLUSIONS: CV lead removal is relatively successful and safe. The presence of local infection and a shorter lead duration may enable successful ST of a CV lead. However, the re-implantation procedure should be well prepared for the complexity related to the right-side approach and occlusion/stenosis of the previous CV.

A 54 Gy in three fractions of stereotactic body radiotherapy using CyberKnife for T1b-2aN0M0 pathologically confirmed non-small cell lung cancer.

OBJECTIVE: Optimal dose-fractionation regimen of stereotactic body radiotherapy for peripheral early-stage non-small cell lung cancer remains unclear. We retrospectively investigated outcomes of stereotactic body radiotherapy using CyberKnife at 54 Gy in three fractions in 26 patients (median age: 76 years) with pathologically confirmed T1b-T2aN0M0 non-small cell lung cancer. METHODS: A 54 Gy in three fractions was prescribed to cover the 99% of gross tumor volume. We estimated cumulative local control, progression-free survival and overall survival rates (Kaplan-Meier method), and toxicity (Common Toxicity Criteria for Adverse Events, version 5.0). RESULTS: All the tumors were located at peripheral area of lung. Mean distance from chest wall to tumor was 6.5 mm (range: 0-32 mm). The patients' pathological diagnoses were: adenocarcinoma: n = 18, squamous cell carcinoma: n = 7 and non-small cell carcinoma: n = 1. Their stages were T1b: n = 9, T1c: n = 14 and T2a: n = 3. Median follow-up was 24 months (range: 6-54). Cumulative 2-year effect rates were local control: 100%, progression-free survival 70% and overall survival: 92%. Twenty patients developed grade one radiation pneumonitis, but grade 2 or greater radiation pneumonitis was not observed. CONCLUSIONS: We found CyberKnife-stereotactic body radiotherapy for pathologically confirmed T1b-T2aN0M0 non-small cell lung cancer to be effective and safe. However, these results should be validated with a larger patient cohort and prospective follow-up monitoring.

Nutcracker syndrome due to chronic aortic dissection.

Nutcracker syndrome (NCS) is known as a status of compression of the left renal vein (LRV) between the abdominal aorta and superior mesenteric artery (SMA). We here report a case of NCS in a Marfan syndrome patient with type B aortic dissection who was presented with sudden gross hematuria. Computed tomography revealed the compression of the LRV sandwiched between the SMA and the dilated dissecting abdominal aorta. The compression was released by surgical intervention and the hematuria was promptly resolved. This report highlights that NCS should be considered as a differential diagnosis of unexplained hematuria in patients with a chronic dissecting aorta.

Coronary artery bypass using bilateral internal thoracic artery grafts in polyarteritis nodosa.

Polyarteritis nodosa (PAN) affects small- and medium-sized arteries but rarely occurs in coronary artery aneurysms and stenosis. For patients with PAN, coronary artery bypass grafting (CABG) can be challenging, especially with respect to graft selection. We performed CABG using a bilateral internal thoracic artery (ITA) graft for a 21-year-old patient with PAN, with successful postoperative outcomes. Arterial grafts have the risk of stenosis in PAN, but the patient's condition was controlled by steroids and immunosuppressants, and angiography showed no stenosis. We decided to use the ITA graft as a bypass conduit and found that long-term follow-up and continuous treatment are necessary.

Study Protocol for a Randomized, Double-Blind, Placebo-Controlled, Phase-II Trial: AdrenoMedullin for Ischemic Stroke Study.

OBJECTIVES: Adrenomedullin (AM), a vasoactive peptide, has strong anti-inflammatory and angiogenic properties, which have been reported to ameliorate the consequences of ischemic stroke in several animal models. After a phase I study in healthy volunteers, two phase II trials of AM for inflammatory bowel diseases have been recently completed. The current AdrenoMedullin For Ischemic Stroke (AMFIS) study aims to assess the safety and efficacy of AM in patients with acute ischemic stroke. MATERIALS AND METHODS: The AMFIS study is an investigator-initiated, randomized, double-blind, phase-II trial. AM or placebo will be administered to patients with non-cardioembolic ischemic stroke within 24 h after stroke onset. In the first cohort of the AMFIS study, patients will be randomly allocated to the investigation treatment A (30 µg/kg of AM in total for 7 days, n = 20) or placebo group (n = 10). In the second cohort, patients will be assigned to the investigation treatment B (56 µg/kg of AM in total for 7 days, n = 20) or placebo group (n = 10). RESULTS: Serious adverse events related to the protocol treatment will be evaluated as the primary outcome. All adverse events will be analyzed as the secondary outcome. Regarding efficacy endpoints, the change in National Institutes of Health Stroke Scale and modified Rankin Scale scores will be compared between investigation treatment and placebo groups. CONCLUSIONS: AM is expected to be a safe and effective treatment for ischemic stroke.

A Nationwide Multi-Center Questionnaire Survey on the Real-World State and Issues Regarding Post-Stroke Complications in Japan.

OBJECTIVES: Post-stroke complications affect stroke survivors across the world, although data on them are limited. We conducted a questionnaire survey to examine the real-world state and issues regarding post-stroke complications in Japan, which represents a super-aged society. MATERIALS AND METHODS: In 2018, a nationwide multi-center questionnaire survey was conducted in the top 500 Japanese hospitals regarding the number of stroke patients treated. Three questionnaires regarding post-stroke complications were mailed to the doctors responsible for stroke management. RESULTS: Responses were obtained from 251 hospitals (50.2%). The chief doctors responsible for stroke management answered the questionnaires. The number of stroke patients in the departments of neurology and neurosurgery was 338.3 ± 195.3 and 295.8 ± 121.8. Hospitals were classified using the categories secondary (n =142) and tertiary hospitals (n = 106); most hospitals were acute hospitals. Dementia was the most common complication (30.9%), followed by dysphagia (29.3%), and apathy (16.3%). Dementia was thought to be more common by neurologists than neurosurgeons, while apathy and bladder-rectal disorder were thought to be more common by neurosurgeons than neurologists (p = 0.001). The most difficult complication to treat was dysphagia (40.4%), followed by dementia (33.9%), epilepsy (4.1%), and fall (4.1%). Dementia was considered to lack clinical evidence regarding treatment (32.8%), followed by dysphagia (25.3%), and epilepsy (14.1%). Epilepsy was considered to lack clinical evidence among hospitals with a larger number of stroke cases (p = 0.044). CONCLUSION: This study revealed the current state and issues regarding post-stroke complications in Japan. Clinicians should be aware of the importance of post-stroke complications, although data on them remain unsatisfactory.

[Hybrid Treatment for Left Internal Thoracic Artery-Pulmonary Artery Fistula with Aneurysm Complicated with Mitral Regurgitation:Report of a Case].

A 78-year-old man with mitral regurgitation incidentally diagnosed with aneurysm of the left internal thoracic artery(LITA) and several internal thoracic artery-pulmonary artery( ITA-PA) fistulas originating from the aneurysm. To prevent rupture of the aneurysm, ITA ligation was performed during surgery for the mitral valve. Because of the complex anatomy surrounding the aneurysm, the main duct of the ITA was ligated at the peripheral and center of the aneurysm, then arterial fistulae were resected as many as possible. Postoperative computed tomography (CT), however, showed patent LITA and contrast material in the aneurysm. Second stage coil embolization procedure was performed with successful results. Intravascular treatment is effective for ITA aneurysms or ITA-PA fistulae because we can clearly visualize and confirm blood flow during operation.

Oral Carriage of Streptococcus mutans Harboring the cnm Gene Relates to an Increased Incidence of Cerebral Microbleeds.

BACKGROUND AND PURPOSE: Cerebral microbleeds (CMB) are associated with stroke and cognitive impairment. We previously reported a high prevalence of CMB in people with Streptococcus mutans expressing Cnm, a collagen-binding protein in the oral cavity. S.mutans is a major pathogen responsible for dental caries. Repeated challenge with S.mutans harboring the cnm gene encoding Cnm induced cerebral bleeding in stroke-prone spontaneously hypertensive rats. The purpose of this longitudinal study is to examine the relationship of cnm-positive S.mutans to the development of CMB. METHODS: We retrospectively investigated patients with stroke receiving oral microbiological examination and head 3T magnetic resonance imaging evaluations twice in the period 2014 to 2019, allowing >180-day interval. Patients with cnm-positive S.mutans were compared with those without. Quasi-Poisson regression models were used to explore associations between cnm-positive S.mutans and the increase in number of CMB between the 2 magnetic resonance imaging scans. RESULTS: A total of 111 patients were identified; 21 (19%) with cnm-positive S.mutans and 90 (81%) without. Clinical history, including blood pressure and the use of antithrombotic agents, were comparable between the 2 groups. New CMB were more commonly observed in patients with cnm-positive S.mutans (52% versus 23%; P=0.008). The incidence of CMB was significantly higher in the group with cnm-positive S.mutans, especially in deep areas, (incidence rate ratios [95% CI], 5.1 [1.9-13.6] for CMB in any brain region; 15.0 [5.4-42.0] for deep CMB), which persisted after adjusting for age, sex, hypertension, and renal impairment (4.7 [1.8-11.9] for CMB in any brain region; 13.9 [4.3-44.5] for deep CMB). CONCLUSIONS: This study demonstrates that cnm-positive S.mutans is associated with an increased incidence of CMB. Treatment for cnm-positive S.mutans infection may be a novel microbiota-based therapeutic approach for stroke and cognitive impairment.