Contrast-enhanced sonography of pancreatic ductal carcinoma using agent detection imaging

Purpose The aim of this study was to evaluate the enhancement behavior of pancreatic ductal carcinoma by contrast-enhanced sonography with agent detection imaging (ADI), and to clarify the origin of microbubble signals by comparisons with histological findings of resected specimens. Methods The subjects were 21 patients with resectable pancreatic carcinoma. The final histological diagnosis was tubular adenocarcinoma in 20 cases, and anaplastic carcinoma in one case. Ultrasound examinations were performed using an Acuson Sequoia 512 series system, and the contrast agent (Levovist) was injected intravenously in doses of 7 ml (300 mg/ml). The ADI signals (in the tumor) were recorded continuously for 30 s after an injection of Levovist (vascular image) and then obtained intermittently (30 s time-intervals) until the signal had diminished in pancreatic tissue (perfusion image). Results Contrast enhancement of the tumor was observed in 71.4% of subjects on the vascular image and 76.3% of subjects on the perfusion image. Enhancement patterns on the vascular image were classified into three types: VI-1 (linear enhancement), VI-2 (spotty enhancement), and VI-3 (no enhancement). VI-1, VI-2, and VI-3 were seen in 9 (42.8%), 6 (28.6%), and 6 (28.6%) of the 21 cases, respectively. Enhancement patterns on the perfusion image were classified into four types: PI-1 (diffuse uneven enhancement), PI-2 (spotty enhancement), PI-3 (peripheral enhancement), and PI-4 (negative enhancement). The incidence of PI-1, PI-2, PI-3, and PI-4 was 4.8%, 42.9%, 28.6%, and 23.8%, respectively. With respect to resectable cases, these enhancement patterns were compared with histological findings, i.e., the distribution of blood vessels in the tumor, remaining pancreatic tissues in the tumor, differentiation of types of adenocarcinoma, volume of stroma, and invasion types of carcinoma. The enhanced patterns consequently corresponded to either the distribution of the blood vessels or the remaining pancreatic tissues in the tumor. Conclusion This study indicated that pancreatic ductal carcinoma is frequently enhanced by microbubbles, and the signals seem to originate from fine blood vessels and the remaining pancreatic tissues in the tumor.     

Effect of plaunotol in combination with clarithromycin or amoxicillin on Helicobacter pylori in vitro and in vivo

Plaunotol, a cytoprotective anti-ulcer agent, has antibacterial activity against Helicobacter pylori. The purpose of the present study was to investigate the effect of plaunotol when combined with clarithromycin or amoxicillin against H. pylori. When combined with clarithromycin, plaunotol showed synergic activity against 11 of 14 strains, and additive activity against the other three strains, by chequerboard titration. When combined with amoxicillin, plaunotol showed additive activity against 10 of 14 strains. No antagonistic effects were seen against any of the strains tested. The interactions between plaunotol and either clarithromycin or amoxicillin were determined by time-kill assay against the Sydney Strain (strain SS1) of H. pylori. The combination of plaunotol with clarithromycin showed synergic activity and with amoxicillin showed additive activity. In a C57BL/6 mouse gastritis model infected with H. pylori SS1, the plaunotol-clarithromycin and plaunotol-amoxicillin combinations both exhibited synergic effects, which allowed the effective dose of clarithromycin to be reduced when co-administered with plaunotol. These results suggest that plaunotol may have a useful role in combination with anti-H. pylori drugs in the treatment of H. pylori-associated diseases.     

Cognitive behavioural therapy with behavioural analysis for pharmacological treatment-resistant chronic insomnia

This study aimed to determine whether (1) cognitive behavioural therapy with behavioural analysis for insomnia (CBTi-BA) is more effective for insomnia and co-morbid depressive symptoms than treatment as usual (TAU) and (2) whether CBTi-BA promotes earlier reduction of the daily dose of hypnotic medication in chronic insomnia resistant to pharmacological treatment. A total of 63 patients with chronic insomnia aged 20–77 years who already received hypnotic medication regularly were assigned to two interventions: combined therapy or TAU alone. The subjects provided demographic information and completed self-rating scales for insomnia and depressive symptoms. After treatment, the combined therapy group showed significant decreases in the symptoms of both insomnia and depression and significant reductions in the daily dose of hypnotic medication compared with the group receiving TAU alone. In the combined therapy group, 71% of the participants reported a reduction in insomnia to normal levels and 79% succeeded in decreasing the daily dose of hypnotics to 50% or less of the baseline dose. These results revealed that CBTi-BA can reduce insomnia and depressive symptoms as well as the daily dose of hypnotic medication in patients with chronic insomnia resistant to pharmacological treatment.     

Myeloid/Natural Killer Cell Precursor Acute Leukemia Accompanied by Homozygous Protein C Deficiency

A patient with myeloid/natural killer (NK) cell precursor acute leukemia who was also homozygous for protein C deficiency was treated and showed a complete remission while he simultaneously received low molecular weight heparin. He presented with fever spikes, lymphadenopathy, and a bulky tumor of the anterior mediastinum. A bone marrow aspirate showed the infiltration of immature lymphoblastoid cells. The patient's diagnosis was determined to be myeloid/NK cell precursor acute leukemia by morphologic and immunophenotypic analysis (CD7(+)CD33(+)CD34(+)CD56(+)). The patient developed a thrombosis in his jugular vein on cannulation of the internal jugular vein. An examination of the serum levels and the activities of proteins C and S demonstrated a slight decrease in the protein C level but an undetectable protein C activity. The patient received the diagnosis of homozygous protein C deficiency, because both parents were found to have heterozygous protein C activity. Treatment of the patient's leukemia included induction chemotherapy (Ara-C and idarubicin) with concomitant administration of low molecular weight heparin for his homozygous protein C deficiency. He achieved a complete remission without expressing any thrombosis during the course of chemotherapy. To our knowledge, this is the first case ever described in which acute myeloid leukemia was complicated with homozygous protein C deficiency.     

Hydroxyapatite Affects the Physicochemical Properties of Contemporary One-Step Self-Etch Adhesives

The study aimed to evaluate the influence of the manipulation surfaces on the physical properties of one-step self-etch adhesives (1-SEAs). Scotchbond Universal (SBU), Clearfil Universal Bond Quick ER (UBQ), and an experimental adhesive (UBQ_exp) were manipulated on different surfaces: manufacturer’s Teflon-based dispensing dish (TD) or hydroxyapatite plate (HA). After manipulation of the adhesives, the pH of each 1-SEA was measured. Samples of each adhesive/manipulation surface were prepared and subjected to water sorption (WS)/solubility (SL) and flexural strength tests. The modulus of elasticity (E) was measured in dry and wet conditions before and after 24 h water storage, and the percentage of variation of E (ΔE) was calculated. Results were analyzed using the t-test with Bonferroni corrections (α = 0.05). When adhesives were manipulated on the HA plate, there was a significant increase in the adhesives’ pH. WS and SL of all 1-SEAs decreased when the HA was used. Only SBU showed higher flexural strength when manipulated on the HA compared to the manipulation on TD under dry and wet conditions. For each 1-SEA, the use of HA resulted in significantly higher E in dry and wet conditions. ΔE of all adhesives was smaller with the manipulation on HA than on TD. It was concluded that the manipulation of 1-SEA on a hydroxyapatite plate considerably affected the adhesives’ properties.     

Vascular endothelial growth factor receptor 2 expression and immunotherapy efficacy in non–small cell lung cancer

It is unclear whether tumor vascular endothelial growth factor receptor 2 expression affects the therapeutic efficacy of immune‐checkpoint inhibitors and antiangiogenic agents. This retrospective, multicenter study included patients with advanced non–small cell lung cancer who were treated with immune‐checkpoint inhibitors. We constructed tissue microarrays and performed immunohistochemistry with an anti‐vascular endothelial growth factor receptor 2 antibody. We analyzed immune and tumor cell staining separately in order to determine their correlation with the objective response rate, progression‐free survival, and overall survival in patients receiving immune‐checkpoint inhibitors. Of 364 patients, 37 (10%) expressed vascular endothelial growth factor receptor 2 in immune cells and 165 (45%) in tumor cells. The objective response rate, progression‐free survival, and overall survival were significantly worse in patients treated with immune checkpoint inhibitor monotherapy who expressed vascular endothelial growth factor receptor 2 in immune cells than those who did not (10% vs 30%, p = 0.028; median = 2.2 vs 3.6 months, p = 0.012; median = 7.9 vs 17.0 months, p = 0.049, respectively), while there was no significant difference based on tumor cell expression (24% vs 30%, p = 0.33; median = 3.1 vs 3.5 months, p = 0.55; median = 13.6 vs 16.8 months, p = 0.31). There was no significant difference in overall survival between patients treated with and without antiangiogenic agents in any treatment period based on vascular endothelial growth factor receptor 2 expression. Immune checkpoint inhibitor efficacy was limited in patients expressing vascular endothelial growth factor receptor 2 in immune cells.     

Necessity of Multi-Step Surgical Treatment for Patients with Interstitial Lung Disease and a Pneumothorax

Purpose: A pneumothorax occurs in 3%–8% of patients with idiopathic pulmonary fibrosis. A pneumothorax may predict a poor outcome in patients with interstitial lung disease (ILD), and it is difficult to treat patients with ILD and a pneumothorax.Patients and Methods: We retrospectively studied data from all 12 patients with ILD and a pneumothorax who underwent surgical treatment at Toho University Omori Medical Center Hospital between 2009 and 2021.Results: Of the 12 patients, 2 had home oxygen therapy preoperatively and were classified with grade IV interstitial pneumonia (IP). Six patients had preoperative pleurodesis and two had postoperative one using auto-blood. Three patients (25%) had multi-step surgery ≥2, and 5 patients had surgical resection of bullae. No patients had postoperative acute exacerbations and all were discharged from the hospital in a stable condition. The 5-year overall survival rate for all patients was 70.0%. The median survival time was not reached. One patient with unclassified IP was doing well 116 months after surgery.Conclusion: Patients with ILD and a pneumothorax were shown to require multi-step surgical treatment and can anticipate long-term survival.     

The Proportion of Long-term Response to Anti-N IgG Antibody after 12 Months for COVID-19 Subclinical Infections and a Longitudinal Survey for COVID-19 Subclinical Infections in 2021

Objective To examine the continuation of antibody prevalence status after 12 months and background factors in antibody-positive subjects following asymptomatic infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods We initially determined the SARS-CoV-2 anti-nucleocapsid protein immunoglobulin G (anti-N IgG) antibody prevalence in 1,603 patients, doctors, and nurses at 65 medical institutions in Kanagawa Prefecture, Japan. We then obtained consent from 33 of the 39 subjects who tested positive and performed follow-up for 12 months. Results Follow-up for up to 12 months showed that a long-term response of the anti-N IgG antibody could be detected in 6 of the 33 participants (18.2%). The proportions with hypertension, using an angiotensin-receptor blocker, and without a drinking habit were higher among the participants with a long-term anti-N IgG antibody response for up to 12 months than among those without a long-term antibody response. Conclusions The proportion of individuals with subclinical COVID-19 who continuously had a positive result for the anti-N IgG antibody at 12 months was low.