Parkinson disease (PD) is a slowly progressive neurodegenerative disease characterized by the loss of dopaminergic neurons and terminals in the nigrostriatal system. Dopamine transporter (DAT) imaging is widely performed for the differential diagnosis of PD and other degenerative parkinsonism from essential tremor, vascular parkinsonism, and drug-induced parkinsonism. DAT is the plasma membrane carrier specific to dopamine neurons that are responsible for re-uptaking dopamine from the synaptic cleft back into the nerve ending. DAT binding might reflect striatal presynaptic dysfunction or DAT expression in PD patients. Longitudinal studies of DAT imaging have reported progressive changes from early PD patients. This imaging may be used as a progressive biomarker. Follow-up DAT imaging for therapeutic interventions has been applied for several anti-parkinsonian drugs. We herein review the progressive changes and therapeutic modification of DAT binding by anti-PD medications in early PD patients.

Objective Endoscopic ultrasound (EUS) is a safe and accurate examination for evaluating the presence of common bile duct stones (CBDSs). The EUS-first approach, where EUS is performed before endoscopic retrograde cholangiopancreatography (ERCP) for patients suspected of having CBDSs, may help reduce the risk of ERCP-related adverse events and save manpower by avoiding unnecessary ERCP. To evaluate the efficacy of the EUS-first approach in patients with suspected CBDSs.

Methods Between April 2012 and March 2016, 104 patients who underwent the EUS-first approach for suspected CBDSs were retrospectively evaluated. The relevant outcomes were the short- and long-term adverse event rates and the ERCP avoidance rate.

Results EUS findings were positive for CBDSs in 52 patients, showed sludge formation or possible CBDSs in 4 patients, and were negative for CBDSs in 42 patients (but positive for other diseases in 6). Sixty-two patients (62/104, 59.6%) underwent ERCP, and proper treatments were successfully performed in all but 1 who underwent only cholangiography. In the remaining 42 patients (42/104, 40.4%), ERCP was omitted based on the EUS findings. Early adverse events were recognized in 0% of the EUS-only group and 8 patients (12.9%) in the EUS+ERCP group (p=0.02). Regarding late adverse events, recurrent CBDSs occurred in 1 patient (2.3%) in the EUS-only group and 2 (3.2%) in the EUS+ERCP group (p=1.0).

Conclusion The EUS-first approach in patients with suspected CBDSs was useful for reducing early adverse events associated with ERCP without increasing the late adverse event rate, as EUS enabled the avoidance of unnecessary ERCP.

Objective The purpose of the present study was to examine the relationship between thrombocytopenia at baseline and in-hospital outcomes in unselected patients undergoing elective percutaneous coronary intervention (PCI) in Japan.

Methods Among a total of 1,247 consecutive elective PCI-treated patients, patients with a baseline platelet count 150,000-449,000/μL and 50,000-149,000/μL were assigned to the normal platelet (n=1,009) and thrombocytopenia (n=226) groups, respectively. The thrombocytopenia group was further divided into the mild thrombocytopenia (100,000-149,000/μL, n=187) and moderate thrombocytopenia (50,000-99,000/μL, n=39) groups.

Results The angiographic success rate of PCI and in-hospital mortality rate did not differ to a statistically significant extent between the normal platelet and thrombocytopenia groups or between the mild thrombocytopenia and moderate thrombocytopenia groups, whereas the moderate thrombocytopenia group had a significantly higher rate of access site-related bleeding complications than the normal platelet group. According to a multivariate analysis, moderate thrombocytopenia was an independent predictor of access site-related bleeding complications.

Conclusion Among patients with mild to moderate thrombocytopenia, elective PCI might be feasible and effective in the short term; however, more attention should be paid to access site-related bleeding complications, particularly in patients with moderate thrombocytopenia.

Objective Depression is common in patients with heart failure (HF) and is a possible risk factor for adverse outcomes. The aim of this study was to determine the prevalence of depression assessed by the 2-item Patient Health Questionnaire (PHQ-2) and the effect of depression on outcomes in Japanese outpatients with HF.

Methods This sub-analysis of a prospective observational study assessed 976 patients with HF (mean age 66±13 years; 26.7% female; 42.7% with an ischemic etiology). Depression was defined as a PHQ-2 score ≥3. The main composite outcome was death from any cause or hospitalization due to worsening HF. PHQ-2 items were extracted from the PHQ-9 results. To evaluate the association of PHQ-2 scores with outcomes, Cox proportional hazards models were evaluated.

Results Fifty-seven (5.8%) patients were diagnosed with depression. During a median follow-up of 21 months, the incidence rates for death from any cause and hospitalization due to worsening HF in patients with and without depression were 2.2 vs. 0.9 per 100 person-years and 6.7 vs. 1.6, p<0.001, respectively. There was a higher incidence of the main outcome in patients with depression than in those without depression (p<0.001). After adjustment for conventional risk factors, depression (PHQ-2 ≥3) was an independent predictor of the main outcome (hazard ratio 2.41, 95% confidence interval 1.14-4.67, p=0.022), and a score for item 1 of the PHQ-2 (loss of interest or pleasure) ≥2 was also an independent risk factor (hazard ratio 3.57, 95% confidence interval 1.85-6.46, p<0.001).

Conclusion Depression as assessed by the PHQ-2 was identified in 5.8% of Japanese outpatients with HF and was associated with outcomes.

Objective Although several studies have reported the relationship between hypoalbuminemia and the clinical outcome, it remains disputable in patients with acute decompensated heart failure (ADHF). We therefore investigated the relationship between hypoalbuminemia on admission and long-term mortality in hospitalized patients following ADHF.

Methods We examined a cohort of 751 consecutive patients who were admitted to the cardiac intensive-care unit between 2007 and 2011 with a diagnosis of ADHF. These patients were divided into 2 groups according to the presence or absence of hypoalbuminemia on admission, which was defined as a serum albumin ≤3.4 g/dL. A propensity score (PS) was calculated to evaluate the effects of variables related to the presence or absence of hypoalbuminemia. The association between hypoalbuminemia and mortality was assessed using two Cox regression models-namely, conventional adjustment and matching patients with and without hypoalbuminemia using the PS.

Results Among the pre-match patients (n=551), 311 (56%) were classified as exhibiting hypoalbuminemia on admission. There were 152 deaths (27.5%), and the median follow-up was 1.9 years. The presence of hypoalbuminemia on admission tended to be associated with increased mortality in the unadjusted model [hazard ratio (HR) 1.32, 95% confidence interval (95% CI) 0.95-1.84; p=0.098] but not in the conventional adjusted model (HR 0.98, 95% CI 0.64-1.52; p=0.938). Even in post-match patients, no association between hypoalbuminemia and mortality was observed (HR 1.09, 95% CI 0.68-1.76; p=0.722).

Conclusion Hypoalbuminemia on admission was not associated with long-term mortality in patients with ADHF, even if PS matching was used.

Objective Biological disease-modifying anti-rheumatic drugs (bDMARDs) represent an important advance in alleviating rheumatoid arthritis (RA), but their effect on rheumatic airway disease (AD) and interstitial lung disease (ILD) is still unclear. This study was performed to evaluate the association of the use of different bDMARDs with new-onset or worsening of RA-AD/ILD.

Methods We performed a retrospective cohort study of RA patients who received bDMARDs and assessed their AD/ILD before and after drug initiation in our hospital over the past 10 years. We evaluated the serial changes in computed tomography (CT), classified patients according to AD/ILD progression, and analyzed associations between clinical characteristics and outcomes.

Results We enrolled 49 patients. Thirty patients received tumor necrosis factor inhibitors (TNFis), 12 received abatacept (ABT), and the remaining 7 received tocilizumab (TCZ). Seventeen patients had ILD, 10 had AD, and 6 had both AD and ILD before the initiation of bDMARDs. New emergence or exacerbation of AD/ILD was observed in 18 patients after drug initiation, while the remaining 31 remained stable or improved. Multiple logistic regression analyses revealed that pre-existing AD was an independent risk factor against the emergence or exacerbation of RA-AD/ILD, and ABT use was a protective factor against it.

Conclusion Our study showed that pre-existing RA-AD is associated with future worsening of RA-AD/ILD, and ABT over other bDMARDs was associated with a better prognosis. Future studies to confirm our results are needed.

Objective The updated guidelines of 2015 for cardiopulmonary resuscitation (CPR) do not recommend the routine use of atropine for cardiopulmonary arrest.

Methods The study population included out-of-hospital cardiac arrest (OHCA) patients with non-shockable rhythm who were encountered at a Japanese community hospital between October 1, 2012 and April 30, 2017.

Results At the outcome, the epinephrine with atropine and epinephrine-only groups had a similar survival rate to that at hospital admission (28.7% vs. 26.7%: p=0.723). The odds ratio (OR) for the survival to hospital admission after the administration of atropine with epinephrine was 1.33 (95% CI 1.09-1.62; p<0.01), while that after the administration of epinephrine was 0.64 (95% CI: 0.55-0.74, p<0.01). The ORs for the survival to hospital admission for patients with pulseless electrical activity in the epinephrine-alone group and the atropine with epinephrine group were 0.62 (95% CI 0.49-0.78; p<0.01) and 1.35 (95% CI 0.99-1.83; p=0.06), respectively, and those for such patients with asystole in the epinephrine-alone group and the atropine with epinephrine group were 0.64 (95% CI 0.53-0.76; p<0.01) and 1.39 (95% CI 1.10-1.77; p<0.01), respectively. The OR for the survival to hospital admission after the administration of atropine sulfate (1 mg) was 2.91 (95% CI 1.49-5.67; p<0.01), while that for the survival to hospital admission after the administration of 0, 2 and ≥3 mg atropine sulfate was 0.38 (95% CI 0.29-0.50; p<0.01), 1.54 (95% CI 0.58-4.08; p=0.38) and 0.23 (95% CI 0.09-0.60; p<0.01), respectively.

Conclusion The addition of atropine (within 2 mg) following epinephrine was a comprehensive independent predictor of the survival to hospital admission for non-shockable (especially asystole) OHCA adults.

A 40-year-old man suffered from short bowel syndrome. Since a large amount of intestinal output and watery diarrhea hampered his quality of life, we tried to control the intestinal output by reducing the secretion of gastric acid with lansoprazole. Because the small intestine was only 10 cm in length and effective absorption of oral lansoprazole was doubtful, we monitored his intragastric pH for 24 hours and confirmed that the holding time above pH 3.0 was 14.5 hours (60.4%). He spent his home life eating porridge during the day, and receiving total parenteral nutrition of 1,100 mL/day at night while taking lansoprazole as an oral tablet (30 mg) once a day.

An 80-year-old man was found to have a reddish depressed lesion on the middle thoracic esophagus. The morphology of the lesion had been almost unchanged for 3 years, but it transformed to a 2-cm depressed lesion with elevated margins and an irregular nodular surface. The lesion was resected endoscopically and ultimately diagnosed as a combined neuroendocrine carcinoma and squamous cell carcinoma with submucosal invasion. The patient was additionally treated with chemoradiotherapy but died of the primary disease eight months after the initial treatment. It is important to elucidate the natural history of this disease at an early stage.

Portal vein thrombosis (PVT) has been reported in many patients with and without liver cirrhosis. The portal vein is a rare site of thrombosis, and various conditions can predispose an individual to PVT. Among those conditions, hereditary thrombophilia has been increasingly reported recently. We herein report the case of a non-cirrhotic 30-year-old man who developed acute PVT with hereditary antithrombin deficiency. Antithrombin (AT) replacement therapy was required along with heparin. Given our experience with this case, we believe that a screening test for prothrombotic disorders, such as AT deficiency, should be considered in cases of PVT.

Two men (24 and 34 years of age) with a single hypervascular liver tumor were admitted to our hospital. The tumors were diagnosed as hepatocellular adenoma (HCA) by an ultrasound-guided biopsy and classified as inflammatory type by immunohistochemical staining. Considering the risk of malignant transformation, they underwent surgical resection. Although the serum levels of protein induced by vitamin K absence/antagonist-II (PIVKA-II) were slightly elevated, they normalized after the resection. The diagnosis of HCA including malignant transformation is often difficult by image findings alone. Careful immunohistochemical examinations are very useful for the diagnosis and classification of subgroups, including malignant transformation. In addition, we proved that HCA without malignant transformation expresses PIVKA-II.

The patient was a 76-year-old man who was treated with nivolumab due to recurrent gastric cancer. A blood examination revealed grade 3 alkaline phosphatase (ALP) elevation. A histopathological examination revealed marked portal infiltration, including eosinophils and CD4+ and CD8+ T lymphocytes, suggesting nivolumab-related cholangitis accompanied by the features of both an immune-related adverse event (irAE) and drug-induced liver injury (DILI) with allergic reaction. The patient's ALP level immediately decreased after the administration of prednisolone. Although nivolumab-related cholangitis, a rare irAE, has been reported to be refractory to steroid therapy, patients with features of irAE and allergic DILI might immediately respond to prednisolone.

A 66-year-old man was admitted to our hospital because of multiple refractory skin ulcers. Based on his severe systemic arterial calcification and severe calcium-phosphate imbalance due to severe kidney dysfunction, we initially considered calciphylaxis. However, a skin biopsy provided a diagnosis of cholesterol crystal embolization. Although we initiated hemodialysis, steroid treatment, and low-density lipoprotein-cholesterol apheresis, he died of multiple intestinal perforation. An autopsy showed cholesterol crystals occluding multiple organ arterioles. This case suggests that skin ulcers in patients with chronic kidney disease may be an important diagnostic hallmark and may be associated with several serious diseases.

A 70-year-old woman was admitted for the evaluation of wheezes and a nodular lesion in the left lung field. She had been diagnosed with rheumatoid arthritis at 45 years of age and was continuously treated with methotrexate (MTX) at 8 mg/week. Bronchoscopic aspiration histology of a hilar lymph node suggested a lymphoproliferative disorder (LPD). After discontinuation of MTX, the lung nodule and wheezes disappeared. Although wheezes are not a usual manifestation of LPD, her clinical course clearly demonstrated an obvious relationship between LPD-induced airway narrowing and wheezes.

Hepatopulmonary syndrome (HPS) and pulmonary arteriovenous malformation (PAVM) are hypoxemic diseases caused by right-to-left shunting but are rarely concomitant with pulmonary hypertension (PH). A 66-year-old woman with chronic hepatitis C was scheduled to undergo liver transplantation. She was referred to our department for hypoxia and an abnormal shadow in the right lung found on a preoperative examination. She was diagnosed with HPS and a PAVM in the right middle lobe. After liver transplantation, PH temporarily developed, but the pulmonary arterial pressure normalized after coil embolization. Combined HPS and PAVM may cause unique changes in pulmonary hemodynamics during treatment.

Sarcoidosis is a multisystem noncaseating granulomatous disorder of unknown etiology that can be found in almost any organ, but symptomatic respiratory muscle involvement is rare. We herein report the case of a 77-year-old woman with diaphragm sarcoidosis diagnosed by a computed tomography (CT)-guided needle biopsy that was successfully treated with a corticosteroid. The patient presented with dyspnea that lasted for two weeks and respiratory failure. CT revealed diffuse diaphragm thickening with contrast enhancement, which might be a characteristic imaging finding for diaphragm myopathy/myositis, including sarcoidosis. A CT-guided needle biopsy proved useful for the diagnosis of diaphragm sarcoidosis.

Encephalopathy is a rare side effect of cephalosporin treatment. We herein present a case of encephalopathy induced by ceftriaxone, a third-generation cephalosporin, in a patient with renal failure. An 86-year-old woman on maintenance hemodialysis received ceftriaxone for Helicobacter cinaedi bacteremia. Her mental status deteriorated during antibiotic treatment, and an electroencephalogram revealed triphasic waves predominantly in the frontal area. Her consciousness improved after the discontinuation of the antibiotic due to the suspicion of ceftriaxone-induced encephalopathy. This is the first reported case of encephalopathy associated with high plasma and cerebrospinal fluid ceftriaxone concentrations, and provides significant evidence for a causal relationship between the administration of ceftriaxone and the onset of encephalopathy.

A 53-year-old man with recurrent episodes of large joint pain and a low-grade fever at irregular intervals for 16 years developed right knee and ankle arthralgia, watery diarrhea, and abdominal pain. Following an ileum and colon biopsy, he was diagnosed with gastrointestinal amyloidosis. We suspected familial Mediterranean fever (FMF) based on his history and administered colchicine; his symptoms subsequently improved. Thus, he was diagnosed with atypical FMF. After tocilizumab administration, the amyloid deposits disappeared. This case suggests that physicians should consider FMF even in cases with atypical symptoms in order to prevent the progression of amyloidosis and that amyloid deposits can be eliminated by interleukin (IL)-6 inhibition.

A 75-year-old woman was admitted with urosepsis due to Escherichia coli infection. After improvement with a ureteral stent and antimicrobial agent, she complained of back pain and showed elevated inflammation marker levels. Arthralgia and arthritis of multiple peripheral joints were noted, and radiography indicated cartilage calcification. Magnetic resonance imaging revealed lumbar facet joint effusion. Her symptoms improved with nonsteroidal anti-inflammatory drug administration. Thus, she was diagnosed with calcium pyrophosphate deposition (CPPD)-related facet joint arthritis (FJA) rather than infectious FJA. CPPD-related FJA is an important differential diagnosis in elderly individuals with a risk of CPPD disease who complain of back pain.

We encountered a case of syndrome of inappropriate antidiuretic hormone secretion (SIADH) caused by duloxetine, serotonin and norepinephrine reuptake inhibitor (SNRI). A 74-year-old woman complaining of severe lethargy was transferred to our emergency department. Her serum sodium level was 109 mEq/L. Plasma hypo-osmolality with urine normo-osmolality was observed, indicating SIADH. Her essential hypertension had long been treated with telmisartan, and she had just started duloxetine 20 mg/day for chronic musculoskeletal pain 4 days prior to admission. On prescribing duloxetine in the primary care setting, clinicians should be aware of the possibility of duloxetine-induced hyponatremia, particularly in combination with telmisartan.