Objective To examine the add-on effects, compared to the existing antidiabetes treatment, of the sodium-glucose cotransporter 2 inhibitor ipragliflozin on glycemic control and the risk factors of cardiovascular disease (CVD) and chronic kidney disease (CKD) in patients with inadequately controlled type 2 diabetes.

Methods This 12-week, randomized, open-label, active-controlled trial included 30 patients with type 2 diabetes who were randomized 1:1 to ipragliflozin and control groups (n=15 each). The ipragliflozin group received 50 mg of ipragliflozin once daily in addition to conventional therapy. The primary outcome was the change in hemoglobin A1c (HbA1c) from the baseline. Secondary outcomes were changes from the baseline in indices of glycemic control, uric acid (UA), renal function, and arterial stiffness.

Results The patients' diminished estimated glomerular filtration rate (eGFR) was alleviated in the ipragliflozin group compared to the control group [difference between groups (Δ) =4.6 (95% confidence interval (CI): 1.5-7.7) mL/min/1.73 m², p=0.006] prior to significant improvements in HbA1c and other parameters, including anthropometric indices and arterial stiffness. Furthermore, ipragliflozin add-on therapy resulted in a greater reduction in serum UA levels than control therapy [Δ=-52.3 (95% CI: -85.5-19.1) μmol/L, p=0.003]. The changes in the eGFR with ipragliflozin treatment were associated with ipragliflozin-mediated changes in the UA, even after adjusting for the age, sex, baseline HbA1c, baseline UA, and baseline eGFR (standardized regression coefficient=-0.535, p=0.010).

Conclusion Ipragliflozin add-on therapy was associated with beneficial renal effects in parallel with reducing serum UA levels.

Objective In Japan, the aging demographic structure is becoming pronounced, and the full-blown graying of society appears not far off, which indicates an increasing population that will require healthcare contact. Klebsiella spp. are major pathogens in healthcare-associated infections, and their importance is increasing. The aim of this study was to clarify the characteristics of Klebsiella spp. chest infections by evaluating the differences in the characteristics of chest infections caused by Klebsiella spp. and pneumoniae.

Methods We conducted a retrospective study of consecutive patients hospitalized with pneumonia, lung abscess/necrotizing pneumonia, and empyema due to Klebsiella spp. and S. pneumoniae for 15 years at our institution in Saitama, Japan.

Patients Patients with chest infections due to Klebsiella spp. (K group, n=76) and S. pneumoniae (S group, n=446) were included.

Results The K group more frequently was male, older, coinfected by Pseudomonas aeruginosa, and had diabetes mellitus, a history of upper digestive system surgery, alcohol drinking habit, a smoking habit, and an impaired premorbid performance status than the S group. The percentages of lung abscesses or necrotizing pneumonia (31.6% vs. 0.9%) and empyema without pulmonary parenchymal shadow (3.9% vs. 0.7%) were higher in the K group than those in the S group. Severity on admission and mortality did not differ between the groups; however, patients in the K group required a longer duration of antibiotics administration and hospital stay than those in the S group.

Conclusion Klebsiella spp. chest infections have some marked characteristics when compared with pneumococcal infections, and our results serve to differentiate Klebsiella spp. infection from pneumococcal infection.

Although a few reports of neuroendocrine tumor (NET) in the stomach or appendix with surrounding micronests have been published, cases of rectal NET are rare. We herein report a unique case of a patient with single rectal NET treated endoscopically. A pathological examination revealed multiple endocrine cell micronests (ECMs) in the submucosal layer around the main NET lesion. Neither lymph node metastasis nor distant metastasis in computed tomography was observed six years after the treatment. Because case reports of multiple ECM are very rare, the significance of malignancy is unclear. It therefore appears to be necessary to accumulate similar cases.

We herein report a case of gastrointestinal (GI) Kaposi's sarcoma (KS) without cutaneous involvement in a 73-year-old man who had received immunosuppressive drugs for granulomatosis with polyangiitis. After one year of prednisolone use, he presented with tarry stool and severe anemia. Endoscopic and pathological examinations revealed bright-reddish protruding lesions with proliferating spindle cells positive for D2-40, CD34, and HHV-8, which are definitively diagnostic of GI-KS. Drug-induced KS without HIV infection or transplantation is extremely rare, and its clinical features remain unknown. Therefore, we conducted a literature review of steroid-induced KS.

We experienced marked efficacy with steroid treatment of three patients with jackhammer esophagus (JHE). An esophageal biopsy revealed eosinophilic esophagitis (EoE) in two patients. One of the patients without EoE had eosinophilia and an increased serum immunoglobulin E level, and endoscopic ultrasonography revealed thickening of the esophageal muscularis propria. Esophageal manometry was used to diagnose all cases of JHE. Treatment consisted of steroid administration, which improved the symptoms and resolved the esophageal muscularis propria thickening in all patients. The esophageal manometry findings also normalized following treatment. Allergic diseases, including EoE, were assumed to have caused JHE.

We examined a 22-year-old woman who was admitted to our hospital with abdominal distention. At 19 years of age, the patient presented with hepatosplenomegaly. She was examined several times in another hospital; however, the cause was unidentified. Our evaluation showed severe pancytopenia and a spleen 13×24 cm in size. The serum levels of angiotensin-converting enzyme and lysozyme were elevated. She was diagnosed with liver sarcoidosis based on non-caseating epithelioid granuloma in liver biopsy tissue. To improve the symptoms, splenectomy was performed, and her pancytopenia and symptoms improved. Sarcoidosis should be considered in cases of massive splenomegaly.

Pancreatic serous cystic neoplasms (SCNs), such as serous cystadenoma (SCA), are generally recognized as benign because malignant counterparts of SCNs have been extremely rare. In clinical practice, pancreatic cystic neoplasms diagnosed as SCNs have been managed by conservative observation, as long as the patients remained asymptomatic. We herein report a case of metachronous ductal adenocarcinoma that was discovered during long-term follow-up of SCN and review the related literature. To our knowledge, this was the first reported case of the local presence of ductal adenocarcinoma adjacent to SCA that was preoperatively diagnosed by endoscopic ultrasound-guided fine-needle aspiration.

A 59-year-old man who was receiving lenvatinib as a third-line tyrosine kinase inhibitor to treat hepatocellular carcinoma and multiple bone metastases complained of general fatigue four months after starting lenvatinib. A blood examination showed unexpectedly elevated serum C-reactive protein (CRP) levels. Computed tomography (CT) revealed rupture of the gallbladder wall, indicating gallbladder perforation. After conservative treatment, the patient received lenvatinib again under informed consent; however, one month later, CT revealed repeated rupture of the gallbladder wall. Gallbladder perforation had again been induced by lenvatinib. For this reason, lenvatinib is strongly considered a causative drug for gallbladder perforation.

A 72-year-old woman was referred to our institution with decompensated congestive heart failure owing to subacute severe aortic regurgitation and mitral regurgitation. Her blood sample tested positive for myeloperoxidase anti-neutrophil cytoplasmic antibody (ANCA). Cardiac computed tomography revealed abnormal thickening and shortening of the aortic valvar leaflets as well as wall thickening of the sinuses of Valsalva. Based on the diagnosis of ANCA-associated vasculitis, predominantly involving the aortic root, prednisolone administration was initiated, which failed to improve the valvar dysfunction. The patient underwent aortic root replacement and mitral annuloplasty. Histopathology confirmed severe inflammation involving both the aortic valvar sinuses and leaflets.

Venous thromboembolism occurs in prothrombotic states, such as malignancy. To prevent fatal pulmonary thromboembolism, an indwelling inferior vena cava (IVC) filter is considered in addition to anticoagulation therapy. We herein report a case of fracture of a retrievable IVC filter in a malignant lymphoma patient. One of the filter arms was fractured and fixed to the IVC wall after one year. Since dislocation of the fractured arm was assessed correctly using three-dimensional computed tomography, we were able to retrieve the main body of the IVC filter successfully. Indications and management of IVC filter fracture should be discussed.

Giant internal carotid artery aneurysms sometimes extend into the sellar region, which rarely but occasionally results in hypopituitarism due to the compression of the normal pituitary gland or hypothalamus. Hyponatremia is a known complication of hypopituitarism. We herein report two cases of hypopituitarism caused by intrasellar aneurysm of different origins, resulting in hyponatremia. Untreated hypopituitarism may lead to lethargy, coma, cardiac arrhythmia, and death. Therefore, we must be alert for the occurrence of giant intrasellar aneurysm, as it causes hypopituitarism. The prompt diagnosis and treatment of hypopituitarism are necessary to prevent this fatal outcome.

A 45-year-old man with idiopathic aplastic anemia required renal replacement therapy (RRT) due to end-stage renal disease (ESRD). We succeeded in inserting the peritoneal dialysis (PD) catheter under cover of frequent red blood cell and platelet infusions because of severe pancytopenia. During the one-year period after starting PD using an ultraviolet-ray sterilization device, he developed severe leukopenia but no PD-related peritonitis or exit site/tunnel infection until he died of pneumonia. This case suggests that PD might be a suitable choice as RRT in ESRD patients with aplastic anemia, even in those with severe pancytopenia.

We encountered a pregnant hemodialysis patient with severe hyperparathyroidism (HPT). Although her disease was considered to be refractory to medical treatment, the serum intact parathyroid hormone (PTH) level remarkably improved without manifestation of hypercalcemia through only strict serum phosphorus control, mainly via intensification of dialysis. The very strong correlation between the serum phosphorus level and serum intact PTH level suggested the possibility of secondary HPT. She ultimately gave birth to a healthy baby. The clinical course of the patient's HPT and the growth of the child have been good for more than six years.

A 26-year-old man with a history of bronchial asthma was found to have high-density shadows along the bronchovascular bundle and in the subpleural area on computed tomography of the chest. Surgical lung biopsy specimens from the right S⁵ showed fibroelastosis in the subpleural and central airway area with alveolar destruction. He was diagnosed with airway-centered fibroelastosis of unknown cause after multidisciplinary discussions. The patient developed pulmonary hypertension and died 6 years later. The patient was younger in comparison to patients in earlier reports and had more obvious subpleural fibroelastic lesions in the upper lobes than in previously described cases.

Invasion of the endobronchial mucosa by cancer cells is frequently seen in small cell lung cancer (SCLC), but an intraluminal polypoid growth pattern is extremely rare. We herein describe the case of a 69-year-old woman with limited-stage SCLC who had a pedunculated mass in the orifice of the right upper bronchus. Thin-section CT of the lung showed an endobronchial protruding mass accompanied by tubular and branching opacities (the so-called finger-in-glove sign) in the right upper lobe bronchus, which were enhanced by contrast media. She responded well to chemotherapy with concurrent radiation therapy. Although very rare, SCLC patients can have intraluminal polypoid growth, as was observed in this case.

Rheumatoid vasculitis (RV) usually occurs in patients with refractory rheumatoid arthritis (RA). An 80-year-old woman was transferred to our hospital because of muscle weakness and paresthesia in all 4 limbs. She had been diagnosed with RA 30 years ago and achieved sustained clinical remission. At presentation, polyarthritis and drop foot were observed, and rheumatoid factor was prominently elevated. A peripheral nerve conduction test revealed mononeuritis multiplex in her limbs. We suspected that RV had developed rapidly despite RA having been stable for many years and started immunosuppression therapy with steroids combined with azathioprine. The treatment prevented worsening of muscle weakness and paresthesia.

We herein report a 65-year-old man with elevated serum IgG4 levels, enlarged thyroid, and renal dysfunction, mimicking IgG4-related disease (IgG4-RD). The definitive diagnosis of IgG4-RD was not established because a tissue biopsy revealed no IgG4-positive cell infiltration or fibrosis. The presence of an M peak in the β fraction, Bence Jones protein in urine, and progressive anemia suggested multiple myeloma (MM). The κ/λ ratio was >100, tumor plasma cells were present at >20% in bone marrow, and immunostaining revealed IgG4-positive plasma cells; therefore, he was diagnosed with IgG4-type MM. Patients with elevated IgG4 levels with no significant mass lesions should undergo systemic examinations to exclude malignancy.

A 47-year-old man was admitted to our hospital because of thrombocytopenia and consciousness disturbance. As his laboratory data showed undetectable activity of a disintegrin-like and metalloproteinase with thrombospondin type 1 motifs 13 (ADAMTS13) and the presence of ADAMTS13 inhibitor, he was diagnosed with acquired thrombotic thrombocytopenic purpura (TTP). Asymptomatic primary Sjögren's syndrome (SS) and primary hypothyroidism were incidentally diagnosed on screening. After initial plasma exchange therapy and pulse corticosteroid therapy, the patient received rituximab therapy for refractory TTP with "inhibitor boosting" and recovered. TTP secondary to primary SS is rare but can trigger refractory TTP. Treatment with rituximab, which is considered "inhibitor boosting," should be considered when re-exacerbation occurs.

Adult-onset Still's disease (AOSD) usually affects young adults. Some cases of elderly-onset Still's disease (EOSD) have been reported, but its clinical features are unclear. We herein report a 74-year-old woman who developed AOSD with macrophage activation syndrome (MAS). We also reviewed 24 previous EOSD cases in patients over 70 years old and compared the findings with overall AOSD. While the clinical features were similar between the two, including the presence of MAS, disseminated intravascular coagulation was more frequent in EOSD than in AOSD. Furthermore, despite a similar frequency of glucocorticoid use, immunosuppressants and biologics were less frequently administered in EOSD than in AOSD. This report highlights the fact that typical AOSD can develop in elderly patients with some characteristic features.

A 54-year-old woman developed drop head syndrome (DHS), Raynaud's phenomenon and creatine kinase (CK) elevation. She did not meet the international classification criteria of dermatomyositis/polymyositis, as we observed no muscle weakness, grasping pain or electromyography abnormality in her limbs, and anti-aminoacyl tRNA synthetase (ARS) antibody was negative. Cervical magnetic resonance imaging and a muscle biopsy of the trapezius muscle revealed myositis findings as the only clinical observations in muscle. These findings, along with her anti-U1-ribonucleoprotein (RNP) antibody positivity and leukopenia, resulted in a diagnosis of mixed connective tissue disease (MCTD). Prednisolone treatment significantly improved her myositis. To our knowledge, this is the first report of DHS as the only muscle complication of MCTD.

A 74-year-old man underwent intravesical bacillus Calmette-Guerin (BCG) therapy for bladder cancer and later presented with lower left back pain. Magnetic resonance imaging of the spine showed high signal intensity, diagnosed as a cystic lesion in the epidural and bilateral intestinal psoas muscle. A computed tomography-guided needle biopsy and histological examination revealed bacteria from the family Mycobacteriaceae, and Mycobacterium bovis was identified using multiplex polymerase chain reaction. If lower back pain appears in a patient who has undergone BCG therapy, it is necessary to test for tuberculous spondylitis. In addition, QuantiFERON is useful for the differential diagnosis of M. bovis BCG infection.

A 42-year-old man was hospitalized due to a fever, orchiodynia, and extremely severe myalgia predominantly in the extremities, which made it difficult for him to stand or walk. He had a history of contact with his son who had acute upper respiratory infection. Based on the characteristic clinical symptoms and detection of the partial sequence of human parechovirus type 3 (HPeV3) in throat swabs as well as stool and serum samples, he was diagnosed with epidemic myalgia associated with HPeV3 infection. Because HPeV3 infection is widespread among children in Japan, HPeV3-associated myalgia should be considered when adult patients manifest such distinguishing clinical characteristics.