Pancreatic microcirculation in acute pancreatitis

We present a review of the microvascular morphology of the pancreas and microstructure of the pancreatic lobule, and report our experimental results of the investigation of pancreatic microcirculation following acute pancreatitis. Impairment of pancreatic microcirculation in the early phase of acute pancreatitis may play a key role in the progression of this disease. Possible contributory mechanisms include increased vascular permeability, reduced blood flow, leukocyte-endothelial cell interaction and intravascular thrombus formation. Using an in-vivo microscope system and off-line computer analysis, we achieved direct visualization and quantification of changes in microvascular permeability and leukocyte behavior in pancreas with acute pancreatitis. Bradykinin and oxygen radicals have been demonstrated to be involved in the increase of vascular permeability in the early stage of caerulein pancreatitis. Leukocyte adherence to the vessels in the pancreatic microcirculation is a secondary event following permeability changes in acute pancreatitis. Leukocyte infiltration during exacerbation of acute pancreatitis is mediated by leukocyte-endothelial cell interaction via leukocyte integrin CD11b/18.     

Bloodstream infection by multidrug‐resistant Streptococcus oralis in a leukemic patient with febrile neutropenia after hematopoietic stem cell transplantation

We reported the case of a patient with leukemia who developed febrile neutropenia after hematopoietic stem cell transplantation. Blood culture results revealed the presence of Streptococcus oralis, while antimicrobial susceptibility testing showed the resistance to penicillin and cephem. Furthermore, isolates were not susceptible to either meropenem or daptomycin but not to vancomycin. S oralis is known to belong to Streptococcus mitis group and be a causative agent of bacteremia in the neutropenic patients, but multidrug resistance of S oralis is rare. Our findings suggest that we might pay attention to the emergence of the microorganisms acquiring multidrug resistance in neutropenic patients.     

A multicentre phase II study of vorinostat in patients with relapsed or refractory indolent B‐cell non‐Hodgkin lymphoma and mantle cell lymphoma

Although initial rituximab‐containing chemotherapies achieve high response rates, indolent B‐cell non‐Hodgkin lymphoma (B‐NHL), such as follicular lymphoma (FL), is still incurable. Therefore, new effective agents with novel mechanisms are anticipated. In this multicentre phase II study, patients with relapsed/refractory indolent B‐NHL and mantle cell lymphoma (MCL) received vorinostat 200 mg twice daily for 14 consecutive days in a 21‐d cycle until disease progression or unacceptable toxicity occurred. The primary endpoint was overall response rate (ORR) in FL patients and safety and tolerability in all patients. Secondary endpoints included progression‐free survival (PFS). Fifty‐six eligible patients were enrolled; 50 patients (39 with FL, seven with other B‐NHL, and four with MCL) were evaluable for ORR, and 40 patients had received rituximab‐containing prior chemotherapeutic regimens. For the 39 patients with FL, the ORR was 49% [95% confidence interval (CI): 32·4, 65·2] and the median PFS was 20 months (95% CI: 11·2, 29·7). Major toxicities were manageable grade 3/4 thrombocytopenia and neutropenia. Vorinostat offers sustained antitumour activity in patients with relapsed or refractory FL with an acceptable safety profile. Further investigation of vorinostat for clinical efficacy is warranted.     

Efficacy of patient-controlled analgesia for management of pain after abdominal operations.

In order to control pain during the early post-operative period, patient-controlled analgesia (PCA) with buprenorphine as an analgesic drug was applied in 23 patients undergoing abdominal operations. With this "on demand" system, the patient was allowed to self-administer narcotic analgesic medication using a programmable infusion pump. Overdose could be minimized with a mandatory lock-out interval between allowable injections. Average total requirement of buprenorphine was 0.355 mg at 48 hr after operation. Nineteen of the 23 (82.6%) patients characterized their pain control as "excellent" or "good". In these patients there existed high correlation between the total number of patient attempts and the number of successful injections. The PCA system was thought to provide improved pain relief at smaller total drug dosages. In addition, earlier and greater spontaneous physical activity was maintained with PCA therapy. The potential for overdose could be minimized, and thereby PCA appears to be an efficacious and safe method of providing for postoperative pain relief.     

Early detection of euglycemic ketoacidosis during thoracic surgery associated with empagliflozin in a patient with type 2 diabetes: A case report

We report the first case of intraoperatively detected euglycemic diabetic ketoacidosis (DKA) associated with sodium–glucose cotransporter 2 inhibitors during thoracic surgery. A 59-year-old man had a 12-year history of type 2 diabetes mellitus treated with insulin and empagliflozin. The patient developed bacterial empyema and was initiated with antibiotics at a local hospital. Owing to the persistence of his symptoms, he was transferred to our hospital after the medication of empagliflozin the day before surgery. After overnight fasting, the patient underwent thoracoscopic debridement and intrathoracic lavage surgery. During this surgery, he was noted to have euglycemic ketosis and acidosis, and diagnosed as euglycemic DKA. Immediately after the consultation in our department, the patient underwent treatment for DKA. He awoke from anesthesia normally and showed no symptoms of DKA. DKA gradually resolved over the next 24 h. Early identification and management are critical for rapid recovery from perioperative euglycemic DKA associated with sodium–glucose cotransporter 2 inhibitors, especially during thoracic surgery.     

Structure-Guided Design of Novel l-Cysteine Derivatives as Potent KSP Inhibitors

l-cysteine derivatives as selective KSP inhibitors. Here, we report further optimizations using docking modeling in the L5 allosteric binding site, which led to the discovery of several high affinity derivatives with two fused phenyl rings in the trityl group giving low nanomolar range KSP ATPase inhibition. The representative derivatives potently inhibited cell growth of HCT116 cells in correlation with KSP inhibitory activities and significantly suppressed tumor growth in the xenograft model in vivo.     

Mortality and risk factor analysis for Candida blood stream infection: A multicenter study

Candida blood stream infection (candidemia) is severe systemic infection mainly develops after intensive medical cares. The mortality of candidemia is affected by the underlying conditions, causative agents and the initial management. We retrospectively analyzed mortality-related risk factors in cases of candidemia between April 2011 and March 2016 in five regional hospitals in Japan. We conducted bivariate and multivariate analysis of factors including causative Candida species, patients' predisposing conditions, and treatment strategies, such as empirically selected antifungal drug and time to appropriate antifungal treatment, to elucidate their effects on 30-day mortality. The study enrolled 289 cases of candidemia in adults. Overall 30-day mortality was 27.7%. Forty-nine cases (17.0%) were community-acquired. Bivariate analysis found advanced age, high Sequential Organ Failure Assessment (SOFA) score, and prior antibiotics use as risk factors for high mortality; however community-acquired candidemia, C. parapsilosis candidemia, obtaining follow-up blood culture, and empiric treatment with fluconazole were associated with low mortality. Logistic regression revealed age ≥65 years (adjusted odds ratio, 2.13) and sequential organ failure assessment (SOFA) score ≥6 (6.30) as risk factors for 30-day mortality. In contrast, obtaining follow-up blood culture (0.38) and empiric treatment with fluconazole (0.32) were found to be protective factors. The cases with candidemia in associated with advanced age and poor general health conditions should be closely monitored. Obtaining follow-up blood culture contributed to an improved prognosis.     

Thromboembolism in lung cancer patients]

We reviewed 649 primary lung cancer patients with special reference to the occurrence of thromboembolism. Thirteen episodes of thromboembolism were detected in 12 (1.8%) of the 649. Eight of the 12 were men, and their mean age was 63. Adenocarcinoma was the predominant cell type. Most patients had an advanced stage of the disease, but in some in the cancer was at an early stage. In 5 cases, the finding of thromboembolisms led to diagnosis of the lung cancer (38.5%). Anticoagulant therapy was performed in 9 cases, of which 8 responded without serious complication. We emphasize the importance of anticoagulant therapy as a therapy indicated for thromboembolism in patients with lung cancer.