Nocturnal blood pressure and cardiovascular disease: a review of recent advances

The accurate measurement, prediction and treatment of high blood pressure (BP) are essential issues in the management of hypertension. Ambulatory blood pressure monitoring (ABPM) has been shown to be superior to clinic BP measurements as ABPM can provide the following important information: (i) the mean BP levels, (ii) the diurnal variation in BP and (iii) the short-term BP variability. Among these parameters, there is increasing evidence that the mean nocturnal BP level is the most sensitive predictor of cardiovascular morbidity and mortality. Furthermore, several studies have shown that less nocturnal BP dipping, defined as less nocturnal BP decline relative to daytime BP, or a high night-day BP ratio was associated with poor prognosis irrespective of the 24-hour BP levels. These findings can be interpreted in at least two ways: namely, high nocturnal BP or less nocturnal BP dipping might be not only a potent risk factor for cardiovascular disease (CVD), but also a marker of pre-existing or concurrent diseases that can lead to nocturnal BP elevation. In this review, we consider the clinical utility of ABPM and in particular focus on the nocturnal BP levels or nocturnal BP dipping as a potent risk factor for CVD. In addition, the clinical management of high nocturnal BP and blunted nocturnal BP dipping with antihypertensive medications is discussed.     

Early aggressive intervention with tocilizumab for rheumatoid arthritis increases remission rate defined using a Boolean approach in clinical practice

The goal of treating rheumatoid arthritis (RA) should be remission, for which a new definition was proposed in 2011. To determine which patients can achieve the new Boolean-based definition of remission in clinical practice, we analyzed factors associated with remission in 123 patients who received tocilizumab for 52 weeks. We found that patients with short disease duration (<4.8 years) had a significantly higher rate of remission (31.7%) than those with longer disease duration, and patient global assessment was the most important factor for achieving remission. Multivariate analysis revealed the following predictors of remission: short disease duration [<4.8 years; odds ratio (OR) 2.5, 95% confidence interval (CI) 1.4-4.7] and lower disease activity [28-joint disease activity score-erythrocyte sedimentation rate (DAS28-ESR) <5.23; OR 2.5, 95% CI 1.2-5.1). In this study, we showed that remission, as newly defined using a Boolean approach, is a realistic goal for patients treated with tocilizumab with short disease duration in real-world clinical practice.     

Study protocol of a multicenter registry of patients with rheumatoid arthritis starting biologic therapy in Japan: Tsurumai Biologics Communication Registry (TBCR) Study

Biologic agents have proven to be effective against rheumatoid arthritis (RA) in clinical trials and post-marketing surveillance (PMS) studies. However, limited follow-up periods and strict criteria for recruitment might lead to an underestimation of adverse events. To document the long-term course of patients with RA treated with biologics in clinical settings, we established the Tsurumai Biologics Communication Registry (TBCR). First, we retrospectively collected data of patients registered for any biologic PMS study or clinical trial at participating institutes. Thus far, thirteen institutes have joined the registry and 860 patients have been identified. Comparing baseline characteristics by age and initiation year of biologics, young patients had significantly less joint damage and dysfunction and a higher dose of concomitant methotrexate (MTX) compared to older patients. Older age and functional class were significantly related to the incidence of adverse events that resulted in discontinuation of the 1st biologic treatment. The TBCR is in its initial stages, and information on all patients newly starting biologic therapy at participating institutes is being collected prospectively. Differences in baseline characteristics by age and initiation year of biologics need to be carefully evaluated in order to report on drug-related survival and long-term prognosis, using follow-up data in the near future.     

Combination therapy with single incision laparoscopic surgery and double-balloon endoscopy for small intestinal bleeding: report of three cases

The clinical introduction of double-balloon endoscopy (DBE) has brought about a revolution in the diagnosis and the treatment of diseases of the small intestine. DBE allows not only direct observation of the entire small intestine, but also interventional therapies, tissue sampling and India ink marking (tattooing). Single incision laparoscopic surgery (SILS) was developed from conventional laparoscopic surgery to further reduce the degree of invasiveness. SILS requires only one umbilical incision, thus resulting in almost scarless surgery. This report presents three cases of small intestinal bleeding successfully treated by SILS following tattooing under DBE. The average operative time was 67 min and average blood loss was 5 ml. All patients immediately recovered without any complications. SILS, in conjunction with presurgical tattooing by DBE for small intestinal bleeding is considered to be an ideal approach in terms of minimal surgical trauma and aesthetics.     

Anatomical measurements to optimize instrumentation for transvaginal surgery

Background

Use of rigid instruments via transvaginal (TV) route has been proposed as a practical alternative to natural orifice translumenal endoscopic surgery (NOTES) using flexible devices. However, its safety has not been fully evaluated for each abdominal organ with different positional relationship to the vagina. The aim of this study is to obtain baseline anatomical data necessary for safer use of rigid TV instruments, by three-dimensional (3-D) radiologic measurements.

Patients and methods

A retrospective study was conducted on 51 consecutive female Japanese patients with aortic aneurysm who underwent whole-body multidetector computed tomography as preoperative evaluation. The gallbladder (GB), esophagogastric junction (EGJ), and spleen were located on 3-D images, and the following were obtained: (1) the distance from the vagina, (2) the transverse deviation from the midline, and (3) the sagittal deviation from the “vagina–promontory (V–P)” line.

Results

The median distance from the vagina was 26.1 cm for GB, 30.6 cm for EGJ, and 31.1 cm for spleen. The transverse deviation from the midline was 17.7° for GB, 7.0° for EGJ, and 12.9° for spleen. The sagittal deviation from the V–P line was 7.6 degrees for GB, ?7.0° for EGJ, and ?10.3° for spleen. The percentage of “negative angle” cases, which means that the target is located “below” the V–P line, was only 9.8 % for GB versus 88 % for EGJ and spleen.

Conclusions

The intra-abdominal length of TV instruments should be more than 35 cm in Japanese population. GB is widely deviated from the midline and therefore can be safely approached even with rigid/straight instruments. Access to more midline and distant targets may suffer from interference by the sacral promontory, and be potentially dangerous in terms of risk of compression injury by rigid and straight instruments.     

Comparison of Billroth I and Roux-en-Y Reconstruction after Distal Gastrectomy for Gastric Cancer: One-year Postoperative Effects Assessed by a Multi-institutional RCT

Purpose

This randomized, controlled trial evaluated the clinical efficacy of Billroth I (BI) and Roux-en-Y (RY) reconstruction at 1 year after distal gastrectomy for gastric cancer.

Methods

The primary end point was the amount of body weight lost at 1 postoperative year, and secondary end points included other items related to nutritional status such as serum albumin and lymphocyte count, as well as endoscopic examination findings of the remnant stomach and esophagus. Of the 332 patients enrolled, 163 were assigned to the BI group and 169 were randomized to the RY group.

Results

The loss in body weight 1 year after surgery did not differ significantly between the BI and RY groups (9.1 % and 9.7 %, respectively, p = 0.39). There were no significant differences in other aspects of nutritional status between the 2 groups. Endoscopic examination 1 year after gastrectomy showed reflux esophagitis in 26 patients (17 %) in the BI group versus 10 patients (6 %) in the RY group (p = 0.0037), while remnant gastritis was observed in 71 patients (46 %) in the BI group versus 44 patients (28 %) in the RY group (p = 0.0013); differences were significant for both conditions. Multivariable analysis showed that the only reconstruction was the independently associated factor with the incidence of reflux esophagitis.

Conclusions

RY reconstruction was not superior to BI in terms of body weight change or other aspects of nutritional status at 1 year after surgery, although RY more effectively prevented reflux esophagitis and remnant gastritis after distal gastrectomy.     

PTK787/ZK222584 Combined with Interferon Alpha and 5-Fluorouracil Synergistically Inhibits VEGF Signaling Pathway in Hepatocellular Carcinoma

Background

The prognosis of patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus remains poor. We previously reported the beneficial effects of interferon alpha (IFN) and 5-fluorouracil (5-FU) combination therapy for these patients. We showed that the mechanism of therapy was regulation of vascular endothelial growth factor (VEGF). Here, we combined IFN/5-FU therapy with the VEGF receptor–selective inhibitor PTK787/ZK222584 (PTK/ZK) and examined the antitumor effects and the mechanism of action.

Methods

We studied two HCC cell lines, PLC/PRF/5 and HuH7, and a human umbilical vein endothelial cell line, HUVEC. We studied the effects of IFN/5-FU with or without PTK/ZK in growth inhibition assays, immunohistochemistry, Western blot analysis, and immunocytochemistry.

Results

In a HuH7 xenograft model, the combination of PTK/ZK and IFN/5-FU significantly inhibited proliferation, induced apoptosis, decreased microvessel density, reduced the number of tumor cells that expressed VEGF receptor 2 (VEGFR-2), and repressed the phosphorylation of Akt in vivo. In HCC cells and HUVECs in vitro, IFN/5-FU plus PTK/ZK repressed the expression of VEGFR-2 and repressed the phosphorylation of VEGFR, Akt, Erk, and p38MAPK.

Conclusions

VEGF signaling inhibition enhanced the antitumor effects of IFN/5-FU therapy on HCC cells and endothelial cells via Erk, Akt, and p38MAPK pathways.

     

Aortic arch thrombosis in the neonate

Aortic arch thrombosis (AAT) of the neonate is rare but life-threatening by fatal compromise associated with thrombotic obstruction of the ascending aorta. We report a neonate with AAT who demonstrated a severe coarctation of the aorta and cerebral hypo-perfusion immediately after birth. Echocardiography confirmed the diagnosis of AAT on the findings of a large thrombus located on the transverse arch and blocking the cervical arterial branches. Low-molecular-weight heparin reduced the size of the thrombus and improved the hemodynamics of coarctation and cerebral perfusion. Echocardiography is a powerful tool to make a diagnosis and to monitor the size and regression of AAT.