Objective Clinically, patients with proton pomp inhibitor (PPI)-resistant gastroesophageal reflux disease (GERD) are very challenging to treat. The aim of this study was to determine the rates of symptom relief and adverse events among PPI-resistant GERD patients that changed their therapy from a PPI to vonoprazan.

Methods Patients with severe gastroesophageal reflux symptoms (total GERD-Q score ≥8) without endoscopic findings of mucosal breaks who changed their medication from a PPI to vonoprazan during a 12-week period from 2015 to 2016 at 2 hospitals were selected. The primary outcome was the self-reported relief of gastroesophageal reflux symptoms. The odds ratio (OR) for the improvement of symptoms was calculated based on an exact binomial distribution using a matched-pair analysis. The secondary outcome was the GERD-Q score and adverse events.

Results Twenty-six patients (6 men) with a mean age of 67.5 years were analyzed. After the therapy was changed from a PPI to vonoprazan, 18 patients (69.2%) reported an improvement, 6 (23.1%) reported no change, and 2 (7.7%) reported an exacerbation of symptoms. A change in therapy was significantly associated with improved self-reported symptoms (OR 9.0, p<0.001). The mean total GERD-Q score during vonoprazan treatment was significantly lower than that during PPI therapy (11.96 vs. 8.92). There were no significant differences in the incidence of adverse events between the therapies.

Conclusion Changing the medication from a PPI to vonoprazan was significantly associated with an improvement in gastroesophageal reflux symptoms. Vonoprazan is one of the most promising treatment options for patients with PPI-resistant GERD.

Objective Hyponatremia is closely associated with the pathophysiology of cirrhosis. However, the association between the serum sodium level and the response to tolvaptan is unclear. This study evaluated the factors related to the tolvaptan response and the prognosis in cirrhosis patients with ascites and hyponatremia.

Methods We retrospectively reviewed the clinical records of cirrhosis patients hospitalized for treatment with tolvaptan. The associations of patient baseline characteristics with the tolvaptan response after one week and of the characteristics after one-month tolvaptan treatment with the prognosis were analyzed.

Results We analyzed 83 cirrhosis patients with ascites, including 34 patients with hyponatremia. The response rates to tolvaptan in patients with serum sodium <130 mEq/L, 130-135 mEq/L, and >135 mEq/L were 20%, 66%, and 58%, respectively (p=0.22). The serum sodium level was associated with the response to tolvaptan [odds ratio=1.18; 95% confidence interval (CI) =1.02-1.37; p=0.029]. In patients with hyponatremia, the serum sodium level after 1-month tolvaptan treatment was increased compared to baseline (132 mEq/L vs. 136 mEq/L, p=0.006), and an increasing serum sodium level was associated with a lower risk of mortality (hazard ratio=0.85; 95% CI=0.75-0.97; p=0.016). The survival rate was higher in patients with an increase in the serum sodium level after 1 month than in patients with a decreased serum sodium level (p=0.023).

Conclusion Tolvaptan treatment was effective in cirrhosis patients with ascites and hyponatremia, but a low serum sodium level was associated with non-responsiveness to tolvaptan. An increased serum sodium level after one-month tolvaptan treatment may positively influence the mortality risk in cirrhosis patients with hyponatremia.

Objective Eplerenone (EPL) is a mineralo-corticoid receptor antagonist that is highly selective and has few side effects. This study was conducted to examine whether or not EPL treatment was able to reverse glomerular hyperfiltration, as an indicator of aldosterone renal action, in primary aldosteronism (PA) patients.

Methods Changes in the estimated glomerular filtration rate (ΔGFR) were examined in 102 PA patients with EPL treatment. Furthermore, the sequential ΔGFR in 40 patients initially treated with EPL followed by adrenalectomy was examined in order to evaluate the extent of the remaining glomerular hyperfiltration in the patients treated with EPL.

Results EPL decreased the GFR at 1 month after treatment. The GFR at baseline was the sole significant predictor for the ΔGFR. Patients initially treated by EPL followed by adrenalectomy showed three different ΔGFR patterns during the treatment, despite having comparable doses of EPL and comparable control of blood pressure and serum potassium levels. The urinary aldosterone excretion was significantly different among these three groups, and the group with no decrease in the GFR after EPL treatment showed greater urinary aldosterone excretion. Glomerular hyperfiltration was completely restored only in 17.5% of our unilateral PA patients after EPL treatment.

Conclusion The present study revealed that blockade of aldosterone action by EPL could, at least partially, reverse glomerular hyperfiltration in PA. Whether or not these differential effects on the GFR affect the long-term outcome needs to be investigated, especially in patients with unilateral PA who do not want adrenalectomy and choose the EPL treatment option.

Objectives We retrospectively investigated the clinical and endocrinological characteristics of adrenal incidentalomas.

Methods We studied 61 patients who had been diagnosed with adrenal incidentalomas and had undergone detailed clinical and endocrinological evaluations while hospitalized. We used common criteria to diagnose the functional tumors, but for sub-clinical Cushing's syndrome, we used an updated set of diagnosis criteria: serum cortisol ≥1.8 μg/dL after a positive response to a 1-mg dexamethasone suppression test if the patient has a low morning adrenocorticotropic hormone (ACTH) level (<10 pg/mL) and a loss of the diurnal serum cortisol rhythm.

Results Of the 61 patients, none (0%) had malignant tumors, 8 (13.1%) had pheochromocytoma, and 15 (24.6%) had primary aldosteronism; when diagnosed by our revised criteria, 13 (21.3%) had cortisol-secreting adenomas (Cushing's syndrome and sub-clinical Cushing's syndrome), and 25 (41.0%) had non-functional tumors. Compared with the non-functional tumor group, the primary aldosteronism group and the cortisol-secreting adenoma group were significantly younger and had significantly higher rates of hypokalemia, whereas the pheochromocytoma group had significantly larger tumors and a significantly lower body mass index.

Conclusion Our study found a larger percentage of functional tumors among adrenal incidentalomas than past reports, partly because we used a lower serum cortisol level after a dexamethasone suppression test to diagnose sub-clinical Cushing's syndrome and because all of the patients were hospitalized and could therefore receive more detailed examinations. Young patients with hypokalemia or lean patients with large adrenal tumors warrant particularly careful investigation.

Objectives Pneumonia is a major cause of death among inpatients at psychiatric hospitals. Psychiatric hospital-acquired pneumonia (PHAP) is defined as pneumonia developed in inpatients at psychiatric hospitals. PHAP is a type of nursing and healthcare-associated pneumonia (NHCAP). The purpose of this study was to clarify the risk factors for mortality among PHAP patients.

Methods We retrospectively reviewed the clinical files of patients transferred to Tokyo Metropolitan Matsuzawa Hospital from psychiatric hospitals for PHAP treatment during the 10-year period from September 2007 to August 2017. We analyzed the clinical differences between the survivors and non-survivors and assessed the usefulness of severity classifications (A-DROP, I-ROAD, and PSI) in predicting the prognosis of PHAP.

Results This study included a total of 409 PHAP patients, 87 (21.3%) of whom expired and 322 (78.7%) of whom survived. The mortality rates, according to the A-DROP classifications, were 4.9% in the mild cases, 21.6% in the moderate cases, 40.7% in the severe cases, and 47.6% in the very severe cases. The mortality rates, according to the I-ROAD classifications, were 9.5% in group A, 34.7% in group B, and 36.2% in group C. The mortality rates, according to the PSI classifications, were 0% in class II and III, 23.1% in class IV, and 44.9% in class V. The mortality rate increased as the severity increased. We identified 3 factors (age ≥65 years, body mass index ≤18.5 kg/m², and bilateral pneumonic infiltration) as significant predictors of mortality. We therefore added two factors (body mass index ≤18.5 kg/m² and bilateral pneumonic infiltration) to the A-DROP classification and established a modified A-DROP classification with a range of 0 to 7. The area under the receiver operation characteristic curves for predicting mortality were 0.699 for the A-DROP classification and 0.807 for the modified A-DROP classification.

Conclusion The mortality rate in PHAP patients tended to increase with increasing classifications of severity. The modified A-DROP classification may be useful for predicting the prognosis of PHAP patients.

Objective We investigated a novel diagnostic scoring system to differentiate Legionella pneumophila pneumonia from Streptococcus pneumoniae pneumonia.

Methods We retrospectively reviewed the clinical data of 62 patients with L. pneumophila pneumonia (L-group) and 70 patients with S. pneumoniae pneumonia (S-group).

Results The serum sodium (Na) levels tended to be lower according to the severity [age, dehydration, respiratory failure, orientation disturbance, low blood pressure (A-DROP)] score in the L-group. On a multivariate analysis, we found that four factors were independent predictive markers for inclusion in the L-group: relative bradycardia [hazard ratio (HR) 5.177, 95% confidence interval (CI): 1.072-24.993, p=0.041], lactate dehydrogenase (LDH) levels ≥292 IU/L (HR 6.804, 95% CI: 1.629-28.416, p=0.009), C-reactive protein (CRP) levels ≥21 mg/dL (HR 28.073, 95% CI: 5.654-139.462, p<0.001), and Na levels ≤137 meq/L (HR 5.828, 95% CI: 1.411-24.065, p=0.015). Furthermore, a total score [ranging from 0 to 4, the sum of the points for each factor (0 or 1)] ≥3 points indicated a higher probability of inclusion in the L-group than in the S-group. The diagnostic accuracy of a total score of 3 had a sensitivity of 36.3%, specificity of 100%, and area under the curve of 0.682 (95% CI: 0.558-0.806, p=0.004), and that of a total score of 4 had a sensitivity 27.4%, specificity of 98.2%, and area under the curve (AUC) of 0.627 (95% CI: 0.501-0.754, p=0.045). The diagnostic accuracy had low sensitivity but high specificity.

Conclusions We found four markers that might be useful for differentiating L-group from S-group and created a novel diagnostic scoring system.

An asymptomatic 70-year-old woman was referred to our hospital because of liver enzyme elevation. Enhanced abdominal computed tomography demonstrated a small, round-shaped tumor with dilation of the common bile duct and main pancreatic duct. A biopsy specimen from the papilla showed mucin-containing cells that were positive for endocrine markers on immunohistochemical staining. Endoscopic snare resection was done, and there was a positive vertical margin on pathology. Pancreaticoduodenectomy was then performed later. The final diagnosis was goblet cell carcinoid, pT2N0M0, pStage IIA [Union for International Cancer Control (UICC) 7th edition]. Ampullary goblet cell carcinoid is an extremely rare disease of which there have been no recent reports.

A 67-year-old woman underwent esophagogastroduodenoscopy to determine the cause of her prolonged epigastric pain. During the examination, a sharp-pointed foreign body was observed; the edge of the object had been embedded in the gastric wall. The object was removed via an endoscope, and the patients' symptoms improved immediately. Based on a dietary history and an electron microscope examination, we identified the object as a stem of mizuna, a potherb mustard. Our report indicates that commonly eaten leafy green vegetables can act as sharp-pointed foreign bodies with the potential to injure the upper gastrointestinal tract.

A 74-year-old Japanese woman was diagnosed with pseudolipomatosis of the cecum and ascending colon. Colonoscopy was performed, which revealed the presence of slightly elevated white lesions, while a magnifying observation showed microbubbles within the mucosa. A month after colonoscopy, the patient was diagnosed with pneumatosis intestinalis. Although the exact pathogenesis is unclear, pneumatosis intestinalis may arise secondary to pseudolipomatosis. This case also indicates that a magnifying observation during colonoscopy may aid in the diagnosis of pseudolipomatosis of the large intestine, since it shows microbubbles within the mucosa, which may be a distinctive feature reflecting the pathology of this disease.

A 27-year-old man bearing an erythropoietic protoporphyria (EPP)-associated ferrochelatase (FECH) mutation was admitted to our hospital for general malaise and marked elevation of the serum levels of hepatobiliary enzymes and bilirubin. Initial treatment with plasma exchange did not reduce the blood protoporphyrin or serum liver enzyme levels, so phlebotomy was started. Surprisingly, weekly phlebotomy normalized the serum levels of liver enzymes, accompanied by a marked reduction in the blood protoporphyrin levels. The clinical course of this case strongly suggests that phlebotomy may be a suitable treatment option for EPP-related hepatopathy.

We report the case of a 75-year-old woman who was found to have hepatitis C virus (HCV) infection in 1987. Before treatment in 2016, she was found to have mixed cryoglobulinemia (MC). Direct-acting antiviral (DAA) treatment produced a sustained virological response 12 (SVR12). She noticed gradual muscle weakness in 2015 and the gradual development of dysarthria and dysphagia in 2017. We performed a muscle biopsy that showed inclusion body myositis (IBM). To the best of our knowledge, this is first case of a patient with HCV infection, MC, and IBM, in which MC and IBM did not improve after an SVR12 was obtained by DAA treatment.

Inferior vena cava (IVC) thrombosis is very rare, particularly in the absence of an apparent congenital caval abnormality or hypercoagulable state. We herein report an unusual case of a healthy and active 62-year-old male bodybuilder with a mass-like IVC thrombus. We placed an IVC filter and began treatment with rivaroxaban. The patient recovered successfully, and the IVC thrombus completely disappeared three months later. This case suggested that extrinsic compression of IVC by a tightened weightlifting belt around the abdomen is a triggering factor of IVC thrombosis, and rivaroxaban, a new oral anticoagulant, may be a useful option for treatment.

Carcinoembryonic antigen (CEA), the level of which is known to increase in both patients with gastrointestinal cancers and those with non-neoplastic conditions, is one of the most widely-used tumor markers. Hypothyroidism is a common endocrinological disorder in which CEA levels can rise, and is sometimes overlooked as a diagnosis in the absence of typical symptoms or thyroid enlargement. We report the cases of two patients with non-goiterous severe hypothyroidism with markedly elevated CEA levels that effectively decreased with levothyroxine replacement therapy alone. Hypothyroidism should be considered as an important cause of unexplained high serum CEA levels in order to avoid unnecessary medical examination.

An 84-year-old Japanese woman with metastatic insulinoma suffered from frequent hypoglycemic events. Continuous glucose monitoring (CGM) confirmed severe and frequent symptomatic/asymptomatic hypoglycemia. After the initiation of everolimus treatment, the hypoglycemic events were rapidly eliminated. CGM revealed that her blood glucose levels were maintained without hypoglycemia throughout the day. Furthermore, everolimus reduced the duration of time above the upper limit (>180 mg/dL) along with the standard deviation and mean amplitude of glycemic excursions. This case shows the potential effects of everolimus on hypoglycemia and glycemic control in a patient with inoperable metastatic insulinoma evaluated by CGM.

We herein describe a case of pulmonary tumor thrombotic microangiopathy (PTTM) with rapidly progressing colon cancer. A 61-year-old man who had been receiving treatment for type 2 diabetes mellitus for 3 years was hospitalized due to critical hypoxemia. Computed tomography, which had not shown any abnormalities 3 months previously, revealed a tumor in the ascending colon, multiple nodules in the liver, and the absence of any lung abnormalities. On day 3 of hospitalization, a sudden onset of severe dyspnea and tachycardia occurred, followed by death. Autopsy revealed microscopic metastatic tumor emboli in multiple pulmonary vessels with fibrin thrombus and intimal proliferation, which led to a diagnosis of PTTM.

A 64-year-old man with the bone marrow metastasis due to malignant pleural mesothelioma (MPM) was diagnosed with anemia, leukoerythroblastosis, thrombocytopenia, and lower back pain. A bone marrow biopsy demonstrated infiltrative malignant mesothelioma lesions in the bone marrow. The patient died within 15 days of the detection of the bone marrow involvement. Physicians should consider performing a bone marrow biopsy to diagnose bone marrow metastasis and treat patients with palliative chemotherapy at an earlier phase of the disease. To our knowledge, this is the first report of an MPM patient having bone marrow metastasis with anemia, leukoerythroblastosis, and thrombocytopenia.

A 75-year-old man visited our hospital complaining of a low-grade fever, dry cough, and chest abnormal shadow. Chest computed tomography revealed a nodule with a cavity in the right upper lobe. Endobronchial ultrasonography (EBUS) of the lesion suggested that the lesion was benign. Actinomyces graevenitzii was cultured from the specimen obtained by bronchoscopy using endobronchial ultrasonography with a guide sheath technique and was identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and 16S rRNA sequencing. The patient was treated with intravenous ampicillin; subsequently, his condition improved. We believe that careful observation of EBUS findings may be useful for the differential diagnosis.

A 63-year-old woman presented to our hospital for cough, sputum, and abnormal shadows on chest X-ray. Schizophyllum commune was isolated from mucous plugs. Positive specific IgE and IgG against the fungi, elevated serum IgE, and mucous plugs with typical histologic findings of allergic bronchopulmonary mycosis (ABPM) led to the diagnosis of ABPM due to S. commune. We initially administered itraconazole unsuccessfully. Changing the antifungal agent to voriconazole resulted in improvement of the symptoms and chest imaging findings. Her ABPM has not relapsed for two years since the cessation of voriconazole, which was administered for one year.

A 64-year-old woman complaining of progressive dyspnea was admitted with recurrence of massive pericardial effusion. The patient had been diagnosed with radiation pericarditis based on a previous case of pericardiocentesis. To make a diagnosis and improve her symptoms, imaging examinations and pericardial fenestration were performed. Because of difficulty making a diagnosis, after some months, pericardiotomy and incision of the epicardium were performed. The patient was ultimately diagnosed with primary malignant pericardial mesothelioma of the epithelioid type. Primary malignant pericardial mesothelioma is a rare tumor that is difficult to diagnose. An antemortem diagnosis can be made by a multidisciplinary evaluation.

A 44-year-old man was referred to our hospital for the treatment of a pulmonary and deep sternal wound tuberculosis infection, which is an extremely rare type of extrapulmonary tuberculosis. Laboratory testing revealed a serum immunoglobulin (Ig) G level of 286 mg/dL, IgA of 22 mg/dL and IgM of 13 mg/dL. We therefore diagnosed him with hypo-gamma-globulinemia. He was treated with anti-tuberculosis medications and intravenous immunoglobulin. At present, the tuberculosis has not relapsed in the past six years. It may be useful to assess the humoral immunity status in tuberculosis patients with a normal T cell function, and immunoglobulin therapy may be beneficial for protecting such patients from reactivation of tuberculosis.

We herein report a rare case of oral mucormycosis following allogeneic hematopoietic stem cell transplantation. Oral mucormycosis due to Rhizopus microsporus manifested as localized left buccal mucositis with a 1-cm black focus before neutrophil recovery. Combination therapy with liposomal amphotericin B was initiated and surgical debridement was performed; however, the patient died due to progressive generalized mucormycosis. Considerable attention needs to be paid to the diagnosis and management of oral mucormycosis in post-transplant patients, thereby suggesting the importance of fully understanding the risk factors.

A 55-year-old woman suffered from hemorrhagic tendency. She had severe thrombocytopenia without any hematological or coagulatory abnormalities, and a bone marrow examination revealed an increased number of megakaryocytes without any abnormal cells or blasts. No lymphadenopathy or hepatosplenomegaly was observed on computed tomography. She was initially diagnosed with immune thrombocytopenic purpura (ITP). None of the treatments administered for ITP produced a response. However, abnormal cells were eventually found during the third bone marrow examination. The pathological diagnosis was mature B-cell lymphoma. Rituximab-containing chemotherapy produced a marked increase in the patient's platelet count, and her lymphoma went into complete remission.

Pulmonary reinfection by Nocardia has been rarely reported. We describe a case of pulmonary reinfection by Nocardia in an immunocompetent patient. An 82-year-old immunocompetent woman with bronchiectasis presented with exacerbation of cough. She had a history of pulmonary nocardiosis three years earlier. At that time, Nocardia species were cultured from the sputum and identified as N. cyriacigeorgica with 16S ribosomal RNA gene sequencing. In the present episode, cultures of sputum and bronchial washing specimens grew N. beijingensis, which was identified with 16S ribosomal RNA gene sequencing. Pulmonary reinfection by different Nocardia species can occur in immunocompetent patients.

We herein report the case of a 61-year-old Japanese cirrhotic patient who developed rat bite fever (RBF) and whose first presentation was serious clinical features mimicking those of Henoch-Schönlein purpura (HSP). In addition to the critical clinical conditions, since the histopathology from purpuric skin eruptions was not inconsistent with that of HSP, therapy with prednisolone was promptly started in order to prevent his death. However, initial blood culture on admission yielded a small and slow-growing bacterial growth, which was gradually revealed by further subculture to be a peculiar bacterium, Streptobacillus moniliformis, leading to a definitive diagnosis of RBF. After the immediate cessation of prednisolone, the patient was treated with a more appropriate antibiotic and consequently made a full recovery. An immunocompromised condition with seriously decompensated liver cirrhosis together with moderately severe chronic kidney disease (CKD) in this patient probably exacerbated the severity of the disease.