Objective The incidence of osteoporosis is increasing with the rapid aging of the Japanese population. Bisphosphonates are first-line agents used for the treatment of osteoporosis, but they can cause upper gastrointestinal mucosal injury. This study investigated symptoms and upper gastrointestinal mucosal injury associated with oral bisphosphonates.

Methods Symptoms were evaluated using the F-scale questionnaire, and esophageal mucosal injury and gastroduodenal ulceration were assessed by endoscopy. Patients were stratified by the type of bisphosphonate (alendronate, risedronate, or minodronate), treatment schedule (once weekly or every four weeks), and the concomitant use of other medications [antithrombotic agents, nonsteroidal anti-inflammatory drugs (NSAIDs), or acid suppressants].

Patients The subjects included 221 patients treated with oral bisphosphonates for at least one month.

Results The median F-scale total score was 4 (0-34), reflux score was 2 (0-20), and the mean dyspepsia score was 2 (0-16). Endoscopy showed esophageal mucosal injury of Grade A or worse (Los Angeles classification) in 22/221 patients (10.0%) and gastroduodenal ulcers in 9 patients (4.1%). The dyspepsia score in patients who took minodronate every four weeks was significantly lower (p<0.05) in comparison to patients who took other bisphosphonates. The dyspepsia score was significantly higher (p<0.05) and mucosal injury was significantly more frequent in patients who also used antithrombotic agents and NSAIDs.

Conclusion Symptoms and upper gastrointestinal mucosal damage were not necessarily frequent or severe in patients treated with bisphosphonates. However, the concomitant use of bisphosphonates with antithrombotic agents and NSAIDs increased both symptoms and mucosal injury. The symptoms were milder in patients using minodronate once monthly.

Objective Persistent renal damage (RD) three months after exposure to contrast media is associated with contrast-induced acute kidney injury (CI-AKI) and poor clinical outcomes. Little is known about the role of preprocedural hydration on persistent RD in patients with chronic kidney disease [CKD; estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m²] undergoing percutaneous coronary intervention (PCI). We therefore examined the use of preprocedural hydration to decrease the incidence of persistent RD.

Methods Between 2012 and 2015, 1,230 consecutive patients undergoing PCI, except for patients with an eGFR ≥60 mL/min/1.73 m², on dialysis, having acute myocardial infarction, or recently having started renin-angiotensin inhibitors, were screened (n=333). Before their index PCI, the 12-h saline group (n=103) received 1 mL/kg/h 0.9% sodium chloride for 12 hours, and the 1-h bicarbonate group (n=63) received 3 mL/kg 154 mEq/L sodium bicarbonate for 1 hour. The control group (n=167) received no pre-procedural hydration. The study outcome of kidney function decline was investigated using the percent-change (%-change) of the calculated creatinine clearance between the baseline value and the lowest value recorded three to six months after index PCI.

Results There was less renal function deterioration in the saline group than in the control group, and the bicarbonate group showed deterioration similar to the other groups (%-change; 12-h saline 2.0±11.3% vs. control −5.6±12.6%, p<0.001; vs. 1-h bicarbonate −1.8±14.1%, p=0.18; 1-h bicarbonate vs. control, p=0.14 ANOVA). A multiple regression analysis adjusted for risk factors for persistent RD showed that saline hydration correlated independently with a higher %-change (r=0.262, p<0.001).

Conclusion Preprocedural 12-h saline may be better than no preprocedural hydration in preventing mid-term renal insufficiency in CKD patients undergoing PCI.

Objective Glucose-lowering drug-induced hypoglycemia is a serious complication and there have been a few reports of seasonal variations in hypoglycemia in patients with type 2 diabetes. The aim of the present study was to examine the association between severe drug-induced hypoglycemia and seasonal variations, and to elucidate the contributing factors.

Methods This retrospective, single center clinical study, analyzed the cases of 125 patients who required emergency hospitalization for severe drug-induced hypoglycemia between January 1, 2001 and December 31, 2014. The period from November to April was defined as the cold season.

Results Severe hypoglycemia occurred more often in the cold season than in the warm season. In the cold season, 62 of 9,981 (0.6%) emergency department visits involved patients who required hospitalization for drug-induced hypoglycemia. In contrast, in the warm season, 27 of 8,649 (0.3%) visits involved patients who required hospitalization for drug-induced hypoglycemia (p=0.002). The proportion of patients treated with sulfonylurea (SU) in the cold season was higher than that in the warm season. Even the use of low-dose SU caused hypoglycemia in the cold season. In the SU-treated group, the proportion of patients with white blood cell and/or C-reactive protein elevation was higher in the cold season than in the warm season (p=0.04).

Conclusion Severe glucose-lowering drug-induced hypoglycemia occured more frequently in the cold season than in the warm season, and was associated with an inflammatory state in patients treated with SU.

Objective Since pulmonary complications are a major cause of mortality in patients with hematologic diseases, their rapid detection and treatment are essential. Bronchoalveolar lavage (BAL) is widely performed to diagnose pulmonary infiltrates not evident with non-invasive investigations; however, reports on its clinical benefits for patients with hematologic diseases are limited. The aim of our study was to investigate the utility of diagnostic bronchoscopy with BAL for those patients.

Methods We retrospectively reviewed the clinical records of 37 consecutive BAL procedures in 33 adult patients with hematological diseases and pulmonary infiltrates with at least 6 months of follow-up between August 2013 and September 2017 (total 747 BAL procedures). The BAL results, ensuing treatment modifications, treatment outcomes, survival times, and adverse events were evaluated.

Results Microbiological findings were detected in 11 (29.7%), even though wide-spectrum antibiotics and antifungal drugs had been empirically administered to most patients (>70%) prior to the bronchoscopy procedure. Overall, 25 of the 37 BAL procedures (67.6%) had some impact on the diagnosis of pulmonary diseases. Patients without specific diagnostic findings from BAL had a significantly poorer survival than those with diagnostic findings via BAL (30-day survival: 33.3% vs. 92.0%; 180-day survival: 8.3% vs. 64.0%). Four patients (12.1%) experienced complications associated with bronchoscopy; there were no procedure-related deaths.

Conclusion BAL seems still important for diagnosing pulmonary infiltrates and/or excluding some of the important respiratory tract pathogens in patients with hematological diseases; furthermore, negative specific diagnostic findings from BAL may be associated with poor prognoses.

Objective We evaluated the clinical effects of a telephone call service for psychological symptoms such as anxiety, depression or apathy in subacute myelo-optico-neuropathy (SMON) patients living alone or with a single caregiver.

Methods Up to 16 SMON patients (4 men, 12 women) and 32 control subjects were evaluated by the geriatric depression scale (GDS), apathy scale (AS) and state and trait anxiety inventory (STAI) forms X-I, including the P and A values for depression, apathy and state anxiety including disturbed peace of mind and enhanced anxiety, respectively, before (pre) and three months after (post) the telephone call service.

Results The SMON patients, especially women, had significantly worse baseline scores in GDS (depression), AS (apathy) and STAI (state anxiety) than control subjects. The automated telephone call service significantly improved the high baseline STAI scores, including the P and A scores (disturbed peace of mind and enhanced anxiety), of SMON patients but not the GDS or AS scores.

Conclusion SMON patients, especially women, living alone or with a single caregiver showed higher baseline depression, apathy and anxiety scores than the control subjects. The present automated telephone call service proved to be a useful care tool for improving the anxiety of SMON patients with high STAI P and A scores.

The standard chemotherapies for neuroendocrine tumors (NETs) are somatostatin analog (SSA) and targeted-agents for NET G1/G2 and platinum-based chemotherapy for neuroendocrine carcinoma (NEC), classified according to the WHO criteria of 2010. We report a case of NET, in which tumors were successfully treated with platinum-containing chemotherapy after remarkable progression with SSA. A 46-year-old man with multiple lymph nodes and liver metastases of unknown primary origin was diagnosed with NET G2 based on the examination of a biopsy specimen. His tumors were stable with SSA for a year, but rapidly became enlarged. A second biopsy revealed NEC. He received cisplatin plus etoposide, and his tumors showed a marked reduction in size.

The patient was diagnosed with ulcerative colitis and received remission induction therapy with prednisolone. While they developed muscle pain in the lower extremities after starting prednisolone, they ultimately achieved clinical remission. After discharge, hematemesis and gastric discomfort developed. Esophagogastroduodenoscopy showed mucosal edema, redness, and oozing bleeding in the gastric body. In addition, the patient had bloody stool and was considered to have a relapse of ulcerative colitis. They therefore received remission induction therapy with tacrolimus. The patient achieved clinical remission again; however, gastric discomfort and muscle pain remained. A drug lymphocyte stimulation test revealed positivity for prednisolone; therefore, the patient was diagnosed with an allergy to prednisolone.

Pancreatic cysts include a variety of benign, premalignant, and malignant lesions. Endometrial cysts in the pancreas are extremely rare lesions that are difficult to diagnose before surgery. We report the case of a 26-year-old patient with a recent episode of left abdominal pain who presented with a large cyst in the pancreatic body. Laboratory results showed white blood cell and C-reactive protein elevation, whereas the patient's tumor marker levels were within the normal range. Distal pancreatectomy with splenectomy was performed. The final histopathological examination confirmed the presence of endometriotic cysts within the pancreas. Only 13 cases of endometriotic cysts of the pancreas have been previously reported. The preoperative diagnosis is challenging, and most patients undergo pancreatic resection because of suspected neoplasms. This case report reviews previous studies and discusses the clinicopathological features, pathogenesis, and appropriate treatment for pancreatic endometrial cysts.

We performed split drug-eluting bead transarterial chemoembolization (DEB-TACE) in a patient with huge unresectable hepatocellular carcinoma and multiple intrahepatic metastases. However, TACE was discontinued at the fourth application because the tumor was fed by the cholecystic artery. As most intrahepatic metastases disappeared following DEB-TACE, the patient was able to undergo radical hepatectomy, and has maintained a complete response. DEB-TACE enables cancer treatment without reducing the liver or renal function. However, it is associated with a risk of ischemia in other organs in patients whose arteries feed both tumors and other organs; thus appropriate selection is required.

A 47-year-old man with ulcerative colitis was transferred to our hospital due to progressive dyspnea. Electrocardiography on admission showed ST elevation in leads II, III, aVF, and V5-V6. Coronary angiography revealed no remarkable coronary stenosis, and left ventriculography showed a depressed left ventricular ejection fraction (EF) of 23%. Although the patient received percutaneous cardiopulmonary support, his EF progressively decreased (7-15%), and both ventricular tachycardia (VT) and high-degree atrial-ventricular block occurred. An endomyocardial biopsy showed eosinophilic infiltration in the myocardium. Steroid therapy improved the patient's EF. However, his severe inferior wall hypokinesis and non-sustained VT remained after the abovementioned treatment.

IgG4-related diseases (IgG4-RDs) have recently been reported in many organs other than the salivary, pancreatic and hepatobiliary systems. A 64-year-old woman was referred to our department for her abdominal fullness and cardiomegaly on chest X-ray. After draining the pericardial fluid, her symptom promptly diminished, and pericardial friction rubbing became clearly audible. Elevated serum levels of IgG and IgG4 and ureteral wall thickening on computed tomography suggested IgG4-RD. After the initiation of oral corticosteroid therapy, the pericardial effusion was resolved, and she has been in a steady-state condition for the past two years.

A 79-year-old Japanese woman presented with consciousness disturbance, hypercalcemia, and hypermagnesemia. She had rheumatoid arthritis and osteoporosis. Three months before admission, she was treated with oral calcitriol for osteoporosis. Two months before admission, she was treated with magnesium oxide for constipation. One month before admission, she underwent articular femoral bone replacement. Two weeks postoperatively, consciousness disturbance and elevated serum calcium levels were observed, and she was transferred to our hospital. On admission, her laboratory data showed elevated serum magnesium and creatinine levels. This is a rare case of coexistent hypercalcemia and hypermagnesemia associated with consciousness disturbance and acute kidney injury.

We herein report two cases of miliary lung metastases from genital carcinoma in uterine cervix and endometrium. Notably, these patients were unable to receive any anti-tumor chemotherapy due to rapid progression causing respiratory failure, and they ultimately died of disease progression within only a month after the first visit to our hospitals. A postmortem examination confirmed the diagnosis of genital large-cell neuroendocrine carcinoma (LCNEC). Chest physicians should be aware of genital LCNEC with a dismal prognostic entity as an important differential diagnosis of miliary lung metastases.

A 71-year-old man presented to our hospital for dyspnea lasting for the past 3 days. Chest X-ray and computed tomography demonstrated right tension pneumothorax, and an electrocardiogram suggested acute inferior myocardial infarction. Despite the relief of tension pneumothorax, the electrocardiographic findings were not completely resolved. Emergency coronary angiography demonstrated an occlusive lesion in the right coronary artery, and percutaneous coronary intervention was performed successfully. Thereafter, the chest tube was removed, and he was discharged. While rare, multiple life-threatening diseases that present with similar symptoms can coexist, so a re-evaluation after performing the initial treatment for one of these diseases is crucial.

A 64-year-old man who presented with repeated bouts of pneumothorax was admitted to our hospital because of gradually progressive dyspnea and repeated episodes of a fever. The physiological, radiological and pathological findings were consistent with pleuroparenchymal fibroelastosis (PPFE). In addition, the serum-specific precipitating antibody for Aspergillus was positive. After the administration of voriconazole, a marked improvement was observed in the imaging and physiological findings. Given this clinical course, we diagnosed the patient with PPFE secondary to aspergillosis. The present case suggests that a therapeutic approach based on the cause of secondary PPFE may improve the prognosis of PPFE.

Nintedanib has been shown to significantly reduce the annual rate of decline in the forced vital capacity (FVC) in patients with idiopathic pulmonary fibrosis (IPF) in previous randomized trials. A 71-year-old man developed exertional dyspnea and was diagnosed with IPF. Four months after treatment with nintedanib, high-resolution computed tomography findings revealed reduced areas of ground-glass opacity and consolidation; 13 months after treatment, the FVC showed improvement from 3.07 to 3.43 L, and the serum Krebs von den Lungen (KL)-6 concentration showed a decline to normal levels. We herein report a patient with IPF who was considered a super responder to nintedanib.

Chronic hypersensitivity pneumonitis is an interstitial pneumonia caused by an immunological reaction to the chronic inhalation of an antigen. Little is known, however, about the pathological change of the pulmonary lesions. A 33-year-old man was diagnosed with chronic bird-related hypersensitivity pneumonitis based on the findings of a surgical lung biopsy and an inhalation provocation test. He underwent lung transplantation at 8 years after the diagnosis because of disease progression. We conclude that the analysis of the explant suggests that the presence of extensive fibrosis in the centrilobular and perilobular area with bridging fibrosis is a form of pathological progression of chronic hypersensitivity pneumonitis.

We herein report two epilepsy patients with the seizure focus in the non-dominant hemisphere manifesting secondarily generalized convulsion (sGC) with retained awareness characterized by a lack of autonomic signs although GC was complicated by respiratory arrest. Given the semiology and electrophysiological findings, the seizure activity was considered to propagate to the supplementary-motor area and the bilateral primary-motor area, with a clinical manifestation of sGC. The absence of autonomic signs during GC can be a key indicator that the seizure remains in the bilateral suprasylvian area and thus does not involve the region necessary for awareness preservation, which may assist in the diagnosis of this atypical epileptic seizure.

We herein report the case of a 60-year-old man with a "target sign" in the left frontal lobe on magnetic resonance imaging (MRI), which is thought to be a specific sign of cerebral toxoplasmosis. ¹⁸F-fluorodeoxyglucose-positron emission tomography showed no increased uptake, and ²⁰¹Tl-single photon emission computed tomography showed the focal uptake in the left frontal lesion. On a brain biopsy, the patient was given a definitive diagnosis of brain metastasis from diffuse large B-cell lymphoma, and cerebral toxoplasmosis was excluded. In the present case, multilayer intensities on MRI may reflect the fast-growing nature of this tumor.

A rare case of Mollaret meningitis characterized by four recurrent episodes of aseptic meningitis during a three-year period is reported. The patient showed a high fever and severe headache accompanied by a high level of cerebrospinal fluid (CSF) cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α). The symptoms and high CSF cytokines were resolved immediately after introducing indomethacin treatment. Reactivation of the latent virus is considered to be the cause of this rare disease, and indomethacin is believed to inhibit the periodic abnormal generation of eicosanoid in the brain, resulting in a reduction in the fever and subsequent inflammation.

Hashimoto's encephalopathy (HE) is a steroid-responsive autoimmune encephalopathy associated with Hashimoto thyroiditis. We herein report a case of HE manifesting "smoldering" limbic encephalitis with persisting symptoms and abnormalities on examinations. Although our patient experienced partial clinical remission after treatment, hippocampal hypermetabolism on [¹⁸F] fluorodeoxyglucose positron emission tomography (FDG-PET) and subclinical seizures on video electroencephalography persisted. Hypermetabolism on FDG-PET was improved by additional prednisolone therapy. Thus, as with other autoimmune limbic encephalitis cases, HE can take a course of "smoldering" encephalitis. FDG-PET and electroencephalogram findings can reflect the disease activity degree in such patients, although with certain neurophysiological and biochemical distinctions.

We report the case of an 80-year-old man with generalized granuloma annulare (GGA) who subsequently developed giant cell arteritis (GCA). Steroid treatment was effective for both diseases in this case. Although cases of concomitant GGA and GCA have rarely been reported, previous studies suggest that common histological characteristics underlie the two diseases. It is therefore necessary to recognize that GGA can be complicated by GCA, particularly when typical symptoms, such as headache and visual disturbance, are present.