Objective The present study evaluated the strategic role of percutaneous transhepatic gallbladder aspiration (PTGBA) for acute cholecystitis (AC) induced by a metallic stent (MS) placed in a malignant biliary stricture in comparison with percutaneous transhepatic gallbladder drainage (PTGBD).

Methods The treatment outcomes for 31 patients who underwent PTGBA as the initial intervention for MS-induced AC were evaluated and compared with those for 12 who underwent PTGBD.

Results The technical success rate was 100% for both groups. PTGBA was ineffective for 11 patients, all of whom recovered with additional intervention, whereas PTGBD was effective for all patients except for 1 who died of sepsis (clinical success rate, 65% vs. 90%, p=0.16). Adverse events (AEs) were observed in only 1 case (3%) in the PTGBA group (mild bile peritonitis). Among the clinically effective cases, AC recurred in 20% of the PTGBA group and 33% of the PTGBD group (p=0.72). In the PTGBA group, the clinical success rate was significantly higher for patients without cancer invasion to a feeding artery of the gallbladder than in those with invasion (75% without invasion vs. 29% with invasion; p=0.036). According to the multivariate analysis, this factor was an independent factor for clinical success of PTGBA (odds ratio, 9.27; p=0.040).

Conclusion Although the clinical success rate of PTGBA for MS-induced AC was lower than that of PTGBD, PTGBA remains a viable option because of its safety and procedural simplicity, especially for cases without tumor invasion to a feeding artery.

Objective This study analyzed changes in the estimated glomerular filtration rate calculated using cystatin C (eGFRcys) and sodium excretion in the urine after administering dapagliflozin as an add-on therapy to conventional treatment for diabetes.

Methods This was a single-center, single-group, prospective interventional study. Dapagliflozin was administered to improve the plasma glucose control in 30 subjects with type 2 diabetes mellitus (age 53±8 years old; 66.6% men). Blood and urine tests were performed before and 6 and 12 months after dapagliflozin administration. The daily sodium excretion was estimated with the Kawasaki formula using second-morning urine samples.

Results The eGFRcys did not markedly differ before and 6 months after the dapagliflozin administration but was significantly increased after 12 months (p<0.001), and the estimated daily sodium excretion was also significantly increased (p<0.001 at 6 months and p=0.002 at 12 months). The systolic and diastolic blood pressures tended to decrease after administration. The HbA1c level after the administration of dapagliflozin tended to be lower in the T3 group, showing the smallest increase in changes in the estimated daily sodium excretion from baseline to 6 months (28.2-107.5 mEq/day), than in the combined groups of T1 (219.5-110.1 mEq/day) and T2 (101.4-28.9 mEq/day). In contrast, the eGFRcys was significantly higher in the combined groups of T1 and T2 than that in the T3 group at both 6 and 12 months (p=0.031 and p=0.007, respectively).

Conclusions Add-on therapy with dapagliflozin increased the urinary sodium excretion and decreased the blood pressure even in the early phase of this therapy. Our results suggest that dapagliflozin add-on therapy may exert nephroprotective effects in subjects with type 2 diabetes mellitus.

Objective The prognostic factors for azacitidine in untreated acute myeloid leukemia (AML) patients ineligible for intensive therapy remain unknown. To identify prognostic factors for azacitidine monotherapy and assist clinicians in deciding whether to use azacitidine monotherapy or other therapies.

Methods We retrospectively analyzed 27 patients with AML who were newly treated with azacitidine between 2013 and 2021 at our hospital. We evaluated potential predictors based on the overall survival (OS).

Results A univariate analysis found that an Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2 and platelet count (Plt) <27,000/μL had a significant negative influence on the OS. A multivariate analysis confirmed that both factors had significant independent adverse effects on the OS. An ECOG PS ≥2 and Plt <27,000/μL were thus assigned 1 point each, and a clinical scoring system was created. Log-rank testing showed that the 0-point group (n=12) had a median OS of 680 days [95% confidence interval (CI) 220-898 days] and a 1-year OS rate of 80.8% (95% CI 42.3-94.9%), the 1-point group (n=11) had a median OS of 90 days (95% CI 62-345 days) and a 1-year OS rate of 18.2% (95% CI 2.9-44.2%), and the 2-point group (n=4) had a median OS of 82 days [95% CI 19-not applicable (NA) days] and a 1-year OS rate of 0% (95% CI NA-NA). The p value of 0.00008 indicated that this scoring was useful.

Conclusion The ECOG PS and Plt can be used to predict the OS with azacitidine monotherapy in untreated AML patients ineligible for intensive therapy.

Objective To investigate the pathogenesis of Philadelphia (Ph)-positive acute lymphocytic leukemia (ALL), we established a lymphoblastoid cell line.

Methods Bone marrow cells from a patient with Ph-positive ALL were enriched by Ficoll-Hypaque centrifugation and cultured in medium with fetal calf serum.

Materials The mononuclear cells of bone marrow aspirate were obtained from an adult man with ALL after he experienced relapse following induction therapy including imatinib mesylate.

Results The cell line termed TNA-M was established, carrying a three-way Ph translocation involving two chromosome 9s and one chromosome 22 as a sole karyotypic abnormality. Furthermore, the cells were positive for CD13 and CD33 in addition to CD19, CD22 and CD79a antigens.

Conclusion This unique cell line is expected to be a valuable tool for understanding the pathogenesis of Ph-positive ALL.

Objectives This study clarified the usefulness of carotid duplex ultrasound (CDU) in evaluating large vessel occlusion (LVO) in patients with acute stroke planned to be treated with mechanical thrombectomy (MT).

Methods This study was single-center, prospective, observational trial. If the ratio of end-diastolic velocity in the common carotid arteries was ≥1.4, or diastolic flow in the affected internal carotid artery (ICA) was absent on CDU, patients were immediately transferred to the angio-suite without additional cerebrovascular imaging. Clinical parameters, including time metrics and outcomes, were evaluated in participants.

Patients We enrolled stroke patients with a National Institutes of Health Stroke Scale score ≥6 and Alberta Stroke Program Early CT score ≥6 in whom MT could be initiated within 6 hours of the stroke onset.

Results Among 140 patients screened during the study period, 48 were ultimately enrolled. Twenty-seven patients were diagnosed with LVO by CDU alone. CDU offered 83% sensitivity and 82% specificity for identifying the occlusion of the ICA or M1 segment of the middle cerebral artery. Among the 29 total patients treated with MT, 20 (67%) showed a modified Rankin Scale score ≤2 at 90 days. The door-to-puncture time was significantly shorter in patients evaluated by CDU alone (34 minutes) than in those evaluated by magnetic resonance angiography after CDU (47.5 minutes, p<0.001).

Conclusion CDU might reduce the time metrics for early initiation of MT with good sensitivity and specificity in identifying LVO.

Objective Prediction of time until and causes of becoming bedridden may help patients with Parkinson's disease (PD) plan their productive lives. This study assessed the relationship between the age at the PD onset and time taken to reach Hoehn and Yahr stage (HY) 5 as well as the causes of motor decline to HY5 in Japanese patients with PD.

Patients We enrolled patients with PD who visited our institute between April 2015 and December 2020, met the UK brain bank criteria, had medical records from the early PD stage, and had had HY5 for over three months. The relationship between the age at the PD onset and the disease duration was evaluated. Data on the possible causes of motor decline to HY5 were obtained from patients, caregivers or medical records.

Results In total, 123 patients with PD (mean age at the PD onset was 69.3 years old; 80 women and 43 men) were included. The age at the PD onset was significantly and negatively correlated with the time until the decline to HY5. Among the 123 patients, 49 reported that the natural course of PD caused the decline to HY5. Possible events that accelerated the motor decline to HY5 included traumatic injury, pneumonia, and other medical or social conditions that might have resulted in reduced daily activities.

Conclusion The time until the decline to HY5 can be estimated based on the age at the PD onset. In addition to natural PD progression, medical or social conditions that reduce physical activity may accelerate motor decline to HY5.

Objectives Coronavirus disease 2019 (COVID-19) reportedly causes thromboembolic complications due to coagulopathy with hypercoagulability and a hypofibrinolytic state. We evaluated the time-course of coagulopathy in patients with severe COVID-19 from admission to discharge from our intensive-care unit (ICU).

Methods We conducted a retrospective study of adults with severe COVID-19 admitted to our ICU between January 20, 2021, and March 31, 2022. We obtained clinical information, laboratory data, and rotational thromboelastometry (ROTEM) parameters at admission and discharge.

Results Fifteen patients were included. Fibrinogen and D-dimer values did not change significantly but were above the normal ranges at admission and discharge. Regarding ROTEM parameters, the maximum clot firmness in fibrinogen function (FIBTEM), a marker of hypercoagulability, did not change significantly but was above the normal range at admission and discharge [median (interquartile range), admission vs. discharge: 31 (25-34) mm vs. 31 (27-32) mm, p=0.589]. The maximum lysis at 60 minutes in the extrinsic coagulation pathway (EXTEM) and intrinsic coagulation pathway (INTEM), as markers of the fibrinolytic function, were both significantly lower at discharge than at admission [median (interquartile range), admission vs. discharge: EXTEM, 3 (2-4) vs. 1 (0-2), p=0.011; INTEM, 3 (1-6) vs. 1 (0-2), p=0.008].

Conclusion This study revealed a persistent hypercoagulable state at ICU discharge and a worse hypofibrinolytic state at discharge than at admission. These results may contribute to a better understanding of coagulopathies in the acute to subacute phases of severe COVID-19.

A 75-year-old man was referred to our hospital with a suspected pancreatic cyst. Imaging tests revealed a 3-cm cystic lesion located ventrally in the duodenal bulbus, which was suspected to be a duplication cyst with its muscularis propria contiguous to that of the duodenum. One year later, the cyst grew to 6 cm due to intracystic hemorrhaging; therefore, surgery was performed. Histopathology revealed a heterotopic pancreas (HP) in the duodenal wall. The diagnosis was a large, non-malignant retention cyst. Inflammation due to impaired outflow of pancreatic juice from the HP was identified as the cause of cyst enlargement.

An 86-year-old Japanese woman was referred to our hospital due to the sudden onset of abdominal pain. Abdominal contrast-enhanced computed tomography (CT) revealed no signs of ischemic bowel; however, laboratory investigations revealed metabolic lactic acidosis, elevation of inflammatory markers, and a remarkable elevation in the serum phosphate level. A prompt surgical evaluation revealed non-occlusive mesenteric ischemia (NOMI). Elevated serum phosphate levels may suggest extensive bowel ischemia or infarction, which can lead to a prompt surgical evaluation, even in the absence of specific radiological findings.

A 75-year-old woman visited our hospital with constipation. Colonoscopy revealed a submucosal tumor in the rectum. She was followed up as a case of mucosal prolapse syndrome. Six years later, she was referred to our hospital due to hematochezia and abdominal pain. Colonoscopy revealed that the submucosal tumor had an ulcerative appearance with bleeding. Low anterior resection was performed. Amyloid protein deposition was detected from the submucosa to subserosa. Other organs showed no evidence of amyloidosis; we therefore diagnosed the patient with localized rectal amyloidosis. This is a rare case of symptomatic localized rectal amyloidosis whose long-term progression was able to be endoscopically observed.

Chronic nausea and vomiting syndrome (CNVS), one of a functional gastroduodenal disorder, was identified in an 8-year-old girl and a 13-year-old boy who had complained of nausea for more than 4 months following coronavirus disease 2019 (COVID-19) due to normality of their head computed tomography and upper gastrointestinal tract images. The patients' symptoms responded quickly to acotiamide, a medication that is effective for treating functional dyspepsia (FD). Despite being a distinct illness from FD, CNVS is also a functional gastrointestinal disorder, and acotiamide may be just as effective for CNVS following COVID-19 as for FD.

A 39-year-old man was admitted because of cardiac arrest. Emergent coronary angiography revealed a preserved coronary blood flow; however, multiple-row detector computed tomography (MDCT) revealed that the proximal right coronary artery (RCA) was running inside the aortic wall, creating proximal stenosis without atherosclerotic changes. Surgical intervention with unroofing was performed; however, postoperative stenosis of the proximal RCA required additional coronary artery bypass grafting (CABG). Intraoperative findings during CABG did not reveal hematoma or coronary dissection. However, MDCT one year after CABG depicted improvement of the RCA and graft stenoses, suggesting that the post-unroof stenosis may have been caused by an inflammatory reaction after surgical intervention.

A 56-year-old man with a 2.5-month history of anorexia developed sweating, weakness, and left hemiplegia and hemispatial neglect. Brain magnetic resonance imaging detected no abnormalities, but magnetic resonance angiography revealed narrowing of the right middle cerebral artery (MCA). The focal neurological signs and narrowing of the MCA resolved after detection and correction of hypoglycemia. Endocrinological examinations indicated adrenal insufficiency. Hemiplegia is a rare but important neurological manifestation of hypoglycemia, although the mechanisms involved remain unknown. Combined hypoglycemia and decreased MCA blood flow associated with vasospasm probably induced regionally severe neuroglycopenia with ischemia, which presented as focal neurological symptoms.

A 42-year-old Japanese woman was admitted for the evaluation of proteinuria. She had a history of four habitual abortions and valvular heart disease, including severe mitral regurgitation and moderate tricuspid regurgitation. A kidney biopsy showed fibrointimal thickening of interlobular arteries, fibrin thrombosis, and associated focal segmental sclerosis. Although the standard test for antiphospholipid (aPL) antibodies was negative, the patient was diagnosed with antiphospholipid syndrome (APS)-related disease by testing for phosphatidylserine dependent anti-prothrombin anticardiolipin antibody, a non-criterial aPL antibody. A kidney biopsy may lead to a diagnosis of APS in patients with negative laboratory test findings for APS.

Pulmonary artery agenesis (PAA) is a rare congenital vascular anomaly usually diagnosed during infancy. We herein report a 67-year-old man with PAA manifesting as massive hemoptysis. Contrast-enhanced computed tomography of the chest revealed the diagnosis of PAA, which we speculated to have resulted in the present event. Detailed angiography provided more accurate information on the pulmonary vasculature and collateral circulation, which helped us plan tailored treatment. Although very rare, we must consider the possibility of PAA in adults with unexplained hemoptysis.

A 50-year-old woman who had previously undergone right hemicolectomy and chemotherapy for colorectal cancer was hospitalized with respiratory failure. Chest computed tomography showed reticulonodular opacities and enlarged lymph nodes. A transbronchial biopsy revealed adenocarcinoma with epidermal growth factor receptor (EGFR) mutations T790M and L861Q. Treatment with the EGFR-tyrosine kinase inhibitor (TKI) osimertinib was started, and she achieved a partial response. We diagnosed her with metastatic lung tumors from colorectal cancer based on additional immunohistochemical staining and the EGFR mutation status (L861Q) of the specimens. Although cases with EGFR mutations have been rarely reported, an EGFR-TKI can be an effective treatment option for colorectal cancer.

Multiple myeloma (MM) is a cancer characterized by the expansion of plasma cells in the bone marrow. Survival times of patients with MM have increased due to the development of novel therapeutic agents. We herein highlight three MM cases that had a poor prognosis despite treatment with novel therapeutic agents. Of note, all patients presented with hyperammonemia that led to a consciousness disorder. The outcome for patients with MM showing high levels of serum ammonia continues to be poor, even with the use of novel therapies. For such patients showing a consciousness disorder, hyperammonemia should be considered as a possible cause.

A 44-year-old woman was admitted to our hospital with a fever, dizziness, and gait disturbance after undergoing allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia followed by graft-versus-host disease. She presented with cerebellar ataxia, nystagmus, and numbness of the lower extremities. Brain magnetic resonance imaging and perfusion scintigraphy showed progressive cerebellar involvement. Cerebrospinal fluid tests showed mildly elevated protein and IgG levels without pleocytosis. Anti-ganglioside antibodies were detected, but their levels did not follow the patient's clinical course. The patient did not respond sufficiently to steroids or other immunotherapies. We herein report the clinical characteristics of this case and a literature review.

A Japanese man in his 60s on medication for chronic lymphocytic leukemia presented with progressive, multifocal neurological manifestations. Magnetic resonance imaging showed a small, solitary region of brainstem involvement. Sensitive real-time polymerase chain reaction testing detected a small amount of JC virus (JCV) DNA (170 copies/mL) with pathogenic mutation in cerebrospinal fluid. We diagnosed the patient with progressive multifocal leukoencephalopathy (PML). The small PML lesion may have caused multifocal neurological symptoms because of its focal brainstem involvement. This case contributes to knowledge regarding the diagnosis and treatment of brainstem PML in the context of hematologic malignancies and other underlying diseases.

Several case reports of patients with both moyamoya syndrome (MMS) and antiphospholipid syndrome (APS) have been published. However, the relationship between MMS and APS has not been clarified. We herein report a patient with MMS who had an ischemic stroke with rapid worsening of stenosis of the middle cerebral artery associated with APS. The patient was triple-positive for antiphospholipid antibodies. Patients with MMS complicated by APS should be closely followed up with vascular imaging.

Anti-mitochondrial antibody (AMA)-associated myopathies represent a homogeneous disease entity with severe arrhythmia and slowly progressive proximal muscle weakness with lordotic posture, irrespective of the presence of primary biliary cholangitis (PBC). We herein report a case of myositis associated with PBC without AMAs. A 48-year-old woman presented with clinical features very similar to AMA-associated myositis, despite negative AMAs. PBC, ascertained by a liver biopsy performed based on mildly elevated liver enzymes, and the efficacy of steroid therapy on muscle weakness confirmed the diagnosis of immune-mediated myositis. When AMAs are negative, a liver biopsy is indispensable for diagnosing treatable PBC-associated myositis.