Role of protein kinase D1 in vasoconstriction and haemodynamics in rats.

AIMS: Protein kinase D (PKD), once considered an effector of protein kinase C (PKC), now plays many pathophysiological roles in various tissues. However, little is known about role of PKD in vascular function. We investigated the role of PKD in contraction of rat aorta and human aortic smooth muscle cells (HASMCs) and in haemodynamics in rats. METHODS AND RESULTS: Isometric tension of rat aortic was measured to examine norepinephrine-induced contraction in the presence of PKD, PKC and Rho-kinase inhibitors. Phosphorylation of PKD1, myosin targeting subunit-1 (MYPT1), myosin light chain (MLC), CPI-17 and heat-shock protein 27 (HSP27), and actin polymerization were measured in the aorta. Phosphorylation of MYPT1 and MLC was also measured in HASMCs knocked down with specific siRNAs of PKD 1, 2 and 3. Intracellular calcium concentrations and cell shortening were measured in HASMCs. Norepinephrine-induced aortic contraction was accompanied by increased phosphorylation of PKD1, MYPT1 and MLC and actin polymerization, all of which were attenuated with PKD inhibitor CRT0066101. PKD1 phosphorylation was not inhibited by PKC inhibitor, chelerythrine or Rho kinase inhibitor, fasudil. In HASMCs, the phosphorylation of MYPT1 and MLC was attenuated by PKD1, but not PKD2, 3 knockdown. In HASMCs, CRT0066101 inhibited norepinephrine-induced cell shortening without affecting calcium concentration. Administration of CRT0066101 decreased systemic vascular resistance and blood pressure without affecting cardiac output in rats. CONCLUSIONS: PKD1 may play roles in aorta contraction and haemodynamics via phosphorylation of MYPT1 and actin polymerization in a calcium-independent manner.

A prospective cohort study of a new electrosurgical unit for preventing colorectal post-endoscopic submucosal dissection coagulation syndrome.

BACKGROUND AND AIM: Post-endoscopic submucosal dissection coagulation syndrome (PECS) is a recognized complication of colorectal endoscopic submucosal dissection (ESD); however, there is a lack of interventions for preventing PECS. We therefore conducted a prospective study to evaluate the utility of maXium, a novel electrosurgical unit, for preventing PECS. METHODS: This single-center, prospective cohort study prospectively enrolled patients undergoing colorectal ESD. The voltage and power of the electrosurgical units were measured. PECS was defined as a visual analog scale (VAS) ≥ 30 mm, an increase of VAS ≥ 20 mm from baseline, body temperature ≥ 37.5°C, or white blood cell count ≥ 10 000/µL after ESD. PECS was classified into type I (without extra-luminal air) and type II (with peri-luminal air). The primary endpoint was the incidence of PECS. A sample size of 92 patients was required to ensure the upper limit of the 90% CI for the incidence of PECS was less than 15%. RESULTS: At resistances greater than 400 Ω, the maXium unit allowed submucosal dissection with lower power than with the VIO300D unit. Ninety-one patients meeting the inclusion criteria were included in the final study analysis. The incidence of PECS was 16% (90% CI, 10-23%), comprising type I (11%) and type II (5%) PECS. Simple extra-luminal air without PECS was observed in 7% of patients. CONCLUSION: Use of the maXium electrosurgical unit did not reduce the incidence of PECS after colorectal ESD; however, the maXium unit had equivalent performance to a conventional electrosurgical unit used for colorectal ESD.

Clinical Impact of Proton Pump Inhibitor and Potassium-Competitive Acid Blocker for Predicting the Curability of Endoscopic Resection in Ulcerative Early Gastric Cancer.

INTRODUCTION: Endoscopic diagnosis is essential for predicting the curability of early gastric cancer (EGC; R0 resection) before treatment, but the relationship between ulcerative lesions and clinical outcomes remains unclear. We aimed to investigate the effect of proton pump inhibitor (PPI) or potassium-competitive acid blocker (P-CAB) on the morphological changes of ulcerative EGCs and its relevance to the clinical outcomes. METHODS: Altogether, 143 patients with differentiated ulcerative EGC that were resected by endoscopic submucosal dissection were retrospectively identified and divided into the following two cohorts depending on their PPI/P-CAB administration status: PPI/P-CAB (n = 76) and non-PPI/P-CAB (n = 67) cohorts. Furthermore, in each cohort, the patients were further divided into the improved and unimproved subgroups based on the ulcerative changes. RESULTS: In the PPI/P-CAB cohort, the deep submucosal invasion and lymphovascular invasion rates were significantly higher in the unimproved subgroup than in the improved subgroup, resulting in a significantly lower R0 resection rate. Contrarily, no significant differences were found between the two subgroups in the non-PPI/P-CAB cohort. The significance of PPI/P-CAB administration was observed only in the ulcerative EGCs with open-type atrophy (R0 resection rate; improved vs. unimproved, 90.9% vs. 48.0%, p = 0.001). When the finding of improved ulcer with PPI/P-CAB administration was used as the indication of endoscopic resection in ulcerative EGCs with open-type atrophy, high sensitivity (78.9%) and accuracy (76.3%) rates for the curability were observed, which were higher than those of conventional endoscopic diagnosis alone (p = 0.021). CONCLUSION: PPI or P-CAB administration might contribute to the potential selection of ulcerative EGCs, enabling endoscopic curative resection.

Synthesis and Characterization of Dibenzothieno[a,f]pentalenes Enabling Large Antiaromaticity and Moderate Open-Shell Character through a Small Energy Barrier for Bond-Shift Valence Tautomerization.

Experimental and theoretical rationalization of bond-shift valence tautomerization, characterized by double-well potential surfaces, is one of the most challenging topics of study among the rich electronic properties of antiaromatic molecules. Although the pseudo-Jahn-Teller effect (PJTE) is an essential effect to provide attractive characteristics of 4nπ systems, an understanding of the structure-property relationship derived from the PJTE for planar 4nπ electron systems is still in its infancy. Herein, we describe the synthesis and characterization of two regioisomers of the thiophene-fused diareno[a,f]pentalenes 6 and 7. The magnetic and optoelectronic properties characterize these sulfur-doped diareno[a,f]pentalenes as open-shell antiaromatic molecules, in sharp contrast to the closed-shell antiaromatic systems of 3 and 5, in which these main cores consist of the same number of π electrons as 6 and 7. Notably, thiophene-fused 6b and 7b showed pronounced antiaromaticity, the strongest among the previous systems, as well as moderate open-shell characteristics. Our experimental and theoretical investigations concluded that these properties of 6b and 7b are derived from the small energy barrier Ea‡ for the bond-shift valence tautomerization. The energy profile of the single crystal of 6b showed the temperature-dependent structural variations assigned to the dynamic mutual exchange between the two Cs-symmetric structures, which was also supported by changes in the chemical shifts of variable-temperature 1H NMR spectra in the solution phase. Both experimental and computational results revealed the importance of introducing heteroaromatic rings into 4nπ systems for controlling the PJTE and manifesting the antiaromatic and open-shell natures originating from the high-symmetric structure. The findings of this study advance the understanding of antiaromaticity characterized by the PJTE by controlling the energy barrier for bond-shift valence tautomerizations, potentially leading to the rational design of optoelectronic devices based on novel antiaromatic molecules possessing the strong contributions of their high-symmetric geometries.

Right ventricular overloading is attenuated in monocrotaline-induced pulmonary hypertension model rats with a disrupted Gpr143 gene, the gene that encodes the 3,4-l-dihydroxyphenyalanine (l-DOPA) receptor.

Pulmonary hypertension (PH) is a severe and progressive disease that causes elevated right ventricular systolic pressure, right ventricular hypertrophy and ultimately right heart failure. However, the underlying pathophysiologic mechanisms are poorly understood. We previously showed that 3,4-l-dihydroxylphenyalanine (DOPA) sensitizes vasomotor response to sympathetic tone via coupling between the adrenergic receptor alpha1 (ADRA1) and a G protein-coupled receptor 143 (GPR143), a DOPA receptor. We investigated whether DOPA similarly enhances ADRA1-mediated contraction in pulmonary arteries isolated from rats, and whether GPR143 is involved in the PH pathogenesis. Pretreating the isolated pulmonary arteries with DOPA 1 µM enhanced vasoconstriction in response to phenylephrine, an ADRA1 agonist, but not to U-46619, a thromboxane A2 agonist or endothelin-1. We generated Gpr143 gene-deficient (Gpr143-/y) rats, and confirmed that DOPA did not augment phenylephrine-induced contractile response in Gpr143-/y rat pulmonary arteries. We utilized a rat model of monocrotaline (MCT)-induced PH. In the MCT model, the right ventricular systolic pressure was attenuated in the Gpr143-/y rats than in WT rats. Phenylephrine-induced cell migration and proliferation were also suppressed in Gpr143-/y pulmonary artery smooth muscle cells than in WT cells. Our result suggests that GPR143 is involved in the PH pathogenesis in the rat models of PH.

Long-term outcomes of nasogastric tube with Gastrografin for adhesive small bowel obstruction.

BACKGROUND: We had previously reported that the administration of Gastrografin through a nasogastric tube (NGT-G) followed by long tube (LT) strategy could be a novel standard treatment for adhesive small bowel obstruction (ASBO); however, the long-term outcomes after initial improvement remain unknown. This study aimed to analyze the long-term outcomes of first-line NGT-G. METHODS: Enrolled patients with ASBO were randomly assigned to receive LT or NGT-G between July 2016 and November 2018. Thereafter, the cumulative surgery rate, cumulative recurrence rate, and overall survival (OS) rate were analyzed. In addition, subset analysis was conducted to determine the cumulative recurrence rate according to colonic contrast with Gastrografin at 24 h. RESULTS: A total of 223 patients (LT group, n = 111; NGT-G group, n = 112) were analyzed over a median follow-up duration of 550 days. The cumulative 1-year surgery rates, cumulative 1-year recurrence rates, and 1-year OS rates in the LT and NGT-G groups were 18.8% and 18.1%, 30.0% and 31.7%, and 99.1% and 96.6%, respectively; no significant differences were observed between both groups. In the NGT-G group, a negative colonic contrast at 24 h demonstrated a higher tendency for future recurrence compared with a positive colonic contrast at 24 h (1-year recurrence rate: negative contrast, 46.9% vs positive contrast, 27.6%). CONCLUSIONS: Gastrografin through a nasogastric tube followed by LT can be a promising treatment strategy for ASBO, with long-term efficacies equivalent to initial LT placement.

Comparison of the Incidence of Periprocedural Myocardial Infarction in Bifurcation Lesions Between Medina (1,1,1) and (0,1,1) in Elective Percutaneous Coronary Intervention.

Periprocedural myocardial infarction (PMI) following percutaneous coronary intervention (PCI) is more frequently observed in true bifurcation lesions such as Medina (1,1,1) and (0,1,1). The aim of this study is to compare the incidence of PMI in elective PCI between Medina (1,1,1) and (0,1,1) bifurcation lesions. This was a retrospective, single-center study. We included 162 true bifurcation lesions, which were divided into the (1,1,1) group (n = 85) and the (0,1,1) group (n = 77). We compared the incidence of PMI between the two groups and performed multivariate logistic regression analysis using PMI as a dependent variable. The incidence of PMI was similar in the (1,1,1) group and the (0,1,1) group (12.9% versus 15.6%, P = 0.658). The final TIMI flow grade of the side branches and that of the main branches were also similar in the two groups. In multivariate logistic regression analysis, Medina classification (1,1,1) was not associated with PMI (odds ratio (OR), 0.996; 95% confidence interval (CI), 0.379-2.621; P = 0.994), but the angle of the side branch < 45° (OR, 3.569; 95% CI, 1.320-9.654; P = 0.012), lesion length in a main vessel (per 10-mm increase) (OR, 1.508; 95% CI, 1.104-2.060; P = 0.010), and absence of side branch protection (OR, 3.034; 95% CI, 1.095-8.409; P = 0.033) were significantly associated with PMI. In conclusion, the Medina (1,1,1) bifurcation lesions did not increase the incidence of PMI as compared to Medina (0,1,1). However, the narrow side branch angle, diffuse long lesion, and absence of side branch protection were significantly associated with PMI. We should pay attention to these high-risk features in the treatment of true bifurcation lesions.

Optimal definition of coagulation syndrome after colorectal endoscopic submucosal dissection: a post hoc analysis of randomized controlled trial.

PURPOSE: Endoscopic clipping closure after colorectal endoscopic submucosal dissection (ESD) did not reduce the incidence of post-ESD coagulation syndrome (PECS) in our recent randomized controlled trial (RCT); however, the definition of PECS is still controversial. The aim of this study is to establish optimal definition of PECS with additional analysis of RCT based on another definition. METHODS: In this multicenter, single-blind RCT, individuals were randomly assigned to colorectal ESD followed by endoscopic clipping closure or non-closure. In this post hoc analysis, the definition of PECS was modified as both localized abdominal pain on visual analogue scale and inflammatory response (fever or leukocytosis), from either localized abdominal pain or inflammatory response in the original study. All participants underwent a computed tomography after ESD, and PECS was classified into type I, conventional PECS without extra-luminal air, and type II, PECS with peri-luminal air. RESULTS: A total of 155 patients (84 in the non-closure group and 71 in the closure group) were analyzed. As a result of criteria modification, 21 type I PECS and four type II PECS cases in the original study, which included patients with clear pain and inflammatory response, were downgraded to no adverse event and simple peri-luminal air, respectively. The frequency of PECS showed no significant difference between non-closure and closure groups. CONCLUSION: Clipping closure after colorectal ESD does not reduce the incidence of PECS regardless of the diagnostic criteria. Either localized abdominal pain or inflammatory response might be optimal criteria of PECS (UMIN000027031). TRIAL REGISTRATION NUMBER: UMIN000027031 DATE OF REGISTRATION: April 18, 2017.

A multicenter, single-blind randomized controlled trial of endoscopic clipping closure for preventing coagulation syndrome after colorectal endoscopic submucosal dissection.

BACKGROUND AND AIMS: Post endoscopic submucosal dissection coagulation syndrome (PECS) occasionally occurs after colorectal endoscopic submucosal dissection (ESD), presenting with localized abdominal pain and inflammation. We conducted a randomized controlled trial (RCT) to assess the usefulness of endoscopic clipping closure to prevent PECS and delayed perforation (DP). METHODS: This is a multicenter, single-blind RCT. Prospectively enrolled patients undergoing colorectal ESD were randomly allocated to endoscopic clipping closure and nonclosure after ESD, stratifying by institution and tumor size. All participants underwent a computed tomography scan after ESD. PECS was defined as visual analog scale (VAS) ≥30 mm, an increase in VAS ≥20 mm from baseline, body temperature ≥37.5°C or white blood cells ≥10,000/µL after colorectal ESD. DP was defined as PECS accompanied by extraluminal air. The preplanned sample size was 320 patients, and the primary endpoint was the rate of PECS/DP. RESULTS: At the planned interim analysis, this trial was terminated by recommendation of the independent data and safety monitoring committee because conditional power with superiority was lower than the preplanned futility limit. Finally, 155 patients were analyzed. The rate of PECS/DP was 16% (95% confidence interval [CI], 8%-23%) in the nonclosure group and 24% (95% CI, 14%-34%) in the closure group (P = .184). All cases of DP were within minor criteria, and all PECS/DP patients were managed conservatively without surgical treatment. Simple periluminal air without PECS was observed in 16% (95% CI, 8%-23%) in the nonclosure group and 10% (95% CI, 3%-17%) in the closure group. CONCLUSION: Endoscopic clipping closure could not reduce the high incidence of PECS/DP after colorectal ESD. (University Hospital Medical Network Clinical Trials Registry number: UMIN000027031.).

IgM response is a prognostic biomarker of primary biliary cholangitis treated with ursodeoxycholic acid and bezafibrate.

BACKGROUND AND AIM: Primary biliary cholangitis (PBC) patients who are refractory to ursodeoxycholic acid (UDCA) are at risk for progression to cirrhosis and liver failure. Bezafibrate could be an alternative second-line therapeutic option in these patients. This study aimed to evaluate the long-term outcome(s) of combined UDCA and bezafibrate therapy in UDCA-refractory PBC patients and identify prognostic factors. METHODS: Among 445 patients treated with UDCA, 150 patients inadequately responded to UDCA monotherapy and received long-term UDCA plus bezafibrate (median, 15 years). Data from these patients were used for this retrospective analysis. RESULTS: Combination therapy resulted in significant improvements in serum biochemistry and liver transplantation risk estimated using the UK-PBC-risk and the GLOBE scores. The cumulative normalization rates of alkaline phosphatase, gamma-glutamyltransferase, and immunoglobulin M (IgM) were significantly higher in patients without cirrhosis-related symptoms or liver-related events than in those with them. Overall, IgM constantly emerged as a significant factor associated with cirrhosis-related symptoms and liver-related events at all time points. Cumulative survival rates were significantly lower in patients with IgM ≥ 240 mg/dL than in patients with IgM < 240 mg/dL. Thus, normalization of IgM levels was a good surrogate predictor of long-term prognosis. None of the patients discontinued combination therapy due to any adverse events during the follow-up period. CONCLUSIONS: Our findings point to the beneficial effects of long-term UDCA plus bezafibrate combination therapy for UDCA-refractory PBC patients, and IgM response can be a useful predictive biomarker of long-term clinical outcomes.

Determinants of Periprocedural Myocardial Infarction in Current Elective Percutaneous Coronary Interventions.

Periprocedural myocardial infarction (PMI) is closely associated with long-term cardiovascular events. The factors associated with PMI are not fully understood. The purpose of this study was to investigate the determinants of PMI in contemporary elective percutaneous coronary intervention (PCI). Overall, 731 elective PCI was divided into the PMI (n = 27) and non-PMI (n = 704) groups. Univariate and multivariate logistic regression analysis was used to find factors associated with PMI. In the univariate analysis, PMI was associated with complex lesion characteristics, such as the lesion length, lesion angle, calcification, and Medina classification. In the multivariate logistic regression analysis, the lesion length (per 10-mm increase: odds ratio (OR), 1.477; 95% confidence interval (CI), 1.161‒1.879; P = 0.002), lesion angle ≥ 45° (versus lesion angle < 45°: OR, 4.244; 95% CI, 1.187‒15.171; P = 0.026), and Medina classification (0,1,1) / (1,1,1) (versus other lesions: OR, 14.843; 95% CI, 6.235‒35.334; P < 0.001) were significantly associated with PMI. Of the 24 lesions with lesion angle ≥ 45° in the PMI group, 14 had final TIMI flow grade ≤ 2 in side branches and 9 had transient slow flow in main branches/transient ST elevation during PCI. Of the 87 lesions with Medina classification (1,1,1) / (0,1,1), 19 had final TIMI grade ≤ 2 in side branches. In conclusion, the lesion length, lesion angle ≥ 45°, and Medina classification (0,1,1) / (1,1,1) were significantly associated with PMI in contemporary elective PCI. Preventing flow limitation in both side branches and main vessels in elective PCI for the diffuse long, angulated, or true bifurcation lesions is important.

Effects of vasopressin during a pulmonary hypertensive crisis induced by acute hypoxia in a rat model of pulmonary hypertension.

BACKGROUND: A pulmonary hypertensive crisis (PHC) can be a life-threatening condition. We established a PHC model by exposing rats with monocrotaline (MCT)-induced pulmonary hypertension to acute hypoxia, and investigated the effects of vasopressin, phenylephrine, and norepinephrine on the PHC. METHODS: Four weeks after MCT 60 mg kg-1 administration i.v., right ventricular systolic pressure (RVSP), systolic BP (SBP), mean BP (MBP), cardiac index (CI), and pulmonary vascular resistance index (PVRI) were measured. PHC defined as an RVSP exceeding or equal to SBP was induced by changing the fraction of inspiratory oxygen to 0.1. Rats were subsequently treated by vasopressin, phenylephrine, or norepinephrine, followed by assessment of systemic haemodynamics, isometric tension of femoral and pulmonary arteries, cardiac function, blood gas composition, and survival. RESULTS: PHC was associated with increased RV dilatation and paradoxical septal motion. Vasopressin increased MBP [mean (standard error)] from 52.6 (3.8) to 125.0 (8.9) mm Hg and CI from 25.4 (2.3) to 40.6 (1.8) ml min-1 100 g-1 while decreasing PVRI. Vasopressin also improved RV dilatation, oxygenation, and survival in PHC. In contrast, phenylephrine increased MBP from 54.8 (2.3) to 96.8 (3.2) mm Hg without improving cardiac pump function. Norepinephrine did not alter MBP. Vasopressin contracted femoral but not pulmonary arteries, whereas phenylephrine contracted both arterial beds. Hence, improvements with vasopressin in PHC might be associated with decreased PVRI and selective systemic vasoconstriction. CONCLUSIONS: In this rat model of a PHC, vasopressin, but not phenylephrine or norepinephrine, resulted in better haemodynamic and vascular recovery.

Pre-anesthetic ultrasonographic assessment of the internal jugular vein for prediction of hypotension during the induction of general anesthesia.

PURPOSE: Severe hypotension caused by anesthetic administration for anesthesia induction, which might cause ischemic stroke, myocardial injury, acute kidney injury and postoperative mortality, should be prevented. Anesthesiologists are familiar with ultrasound examination of the internal jugular vein (IJV). This study aimed to clarify whether ultrasonographic IJV evaluation just before induction could predict the occurrence of such hypotension. METHODS: Adult patients undergoing surgery under general anesthesia were enrolled after excluding patients with cardiovascular disease or ASA-PS ≥ III. Ultrasonographic IJV images were recorded in both the supine and 10° Trendelenburg positions immediately before induction. Using these images, IJV area (IJV-A), diameter and change rate with posture were measured. Hypotension during induction was defined as mean BP < 60 mmHg or > 30% decrease from baseline. RESULTS: Hypotension during induction was observed in 37 of 82 patients. IJV-A in the Trendelenburg position was 2.02 ± 0.86 and 1.72 ± 0.68 in the hypotensive and non-hypotensive groups, respectively (P = 0.08). Logistic regression analysis performed using age, use of calcium antagonists, angiotensin converting enzyme inhibitors/angiotensin receptor blockers, baseline mean BP and IJV-A in the Trendelenburg position as variables showed that IJV-A in the Trendelenburg position was an independent predictor of hypotension, with an adjusted odds ratio of 3.11 (95% CI 1.07-9.03, P = 0.04). Area under the curve was 0.595 (95% CI 0.469-0.722) for IJV-A in the Trendelenburg position. CONCLUSION: IJV-A in the Trendelenburg position was an independent predictor of hypotension during induction. Further study is required to examine the diagnostic accuracy of IJV-A as a predictor for hypotension during induction.

[Tricuspid Valve Infective Endocarditis with Ventricular Septal Defect].

Right-sided infective endocarditis (IE) accounts for 3-14% of all cases of IE. Compared with leftsided IE, its antibiotic treatment is more effective. Therefore, the timing of its surgical treatment is still controversial. We report 2 cases of tricuspid valve IE and ventricular septal defect (VSD) associated with multiple lung abscesses and infarctions. After successful antibiotic treatment, they underwent vegetectomy, tricuspid valve plasty and VSD patch closure. Antibacterial treatment preceding surgical treatment is effective for tricuspid endocarditis complicated with multiple lung abscesses.

[Myocardial Ischemia in Acute Type A Aortic Dissection; Coronary Artery Dissection and Functional Ischemia].

Myocardial ischemia due to acute type A dissection is a fatal complication. This study was undertaken to evaluate the surgical results of acute type A aortic dissection with myocardial ischemia. Between 1986 and 2014, 364 patients were treated for acute type A dissection in our hospital. Twenty-four patients were underwent myocardial revascularization. Preoperative coronary artery stent placement was involved in 2, coronary-artery bypass grafting (CABG) 18 (right 12, left 4, both 2), reCABG 2, and Carrel patch with coronary orifice restoration 2. Seven of CABG group had no symptom of myocardial ischemia, but right coronary artery was circumferentially detached from the intimal ostia. Hospital mortality was 20.1% in patients who underwent CABG. Sixteen patients with significant electrocardiogram ischemic change were not undertaken with CABG, because coronary artery was not involved by dissection. In these cases, acute aortic valve regurgitation, loss of backward pressure from distal aorta, or valve formation by intimal tear in ascending aorta might decrease diastolic pressure at aortic root and make myocardial ischemia.

[Epidural Anesthesia with Non-invasive Positive Pressure Ventilation for Laparotomy in a Patient with Amyotrophic Lateral Sclerosis].

In patients with amyotrophic lateral sclerosis (ALS), general anesthesia carries a significant risk of respiratory complications and may result in prolonged intubation. Epidural anesthesia may be a feasible alternative in selected cases but may impair respiratory function by producing intercostal muscle weakness. Here, we present a case of ALS who underwent emergency laparotomy that was successfully managed with epidural anesthesia and non-invasive positive pressure ventilation.

Effects of rosuvastatin versus atorvastatin on small dense low-density lipoprotein: a meta-analysis of randomized trials.

In addition to their high-intensity effects on the reduction in low-density lipoprotein (LDL) levels, rosuvastatin and atorvastatin would be expected to also reduce small dense LDL (sdLDL) levels. To determine which reduces sdLDL levels more, we performed the first meta-analysis and meta-regression of randomized head-to-head trials of rosuvastatin versus atorvastatin therapy. MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched through April 2012. Eligible studies were prospective, randomized controlled trials of rosuvastatin versus atorvastatin therapy reporting final sdLDL (directly measured or calculated) levels as an outcome. For each study, data regarding final sdLDL levels in both the rosuvastatin and atorvastatin groups were used to generate mean differences (MD) and 95 % confidence intervals (CI). Meta-regression analysis was performed to determine whether the effects of rosuvastatin therapy were modulated by the prespecified factors. Of 159 potentially relevant articles screened initially, 28 reports of randomized trials enrolling a total of 7802 patients were included. Pooled analysis suggested a significant reduction in final sdLDL levels among patients randomized to rosuvastatin versus atorvastatin therapy (MD, -1.56 mg/dl; 95 % CI, -2.30 to -0.83 mg/dl; P < 0.0001). The meta-regression coefficients were statistically significant for the baseline LDL/sdLDL level and the difference in LDL changes between the two groups. In conclusion, rosuvastatin rather than atorvastatin therapy is likely more effective in reduction of sdLDL levels. It should be further investigated whether the reduction in sdLDL levels implies overt clinical benefits of rosuvastatin over atorvastatin.

Circulating interleukin-6 levels are associated with abdominal aortic aneurysm presence: a meta-analysis and meta-regression of case-control studies.

BACKGROUND: In a number of relatively small-size studies, investigators have measured and compared circulating interleukin-6 (IL-6) levels in cases with abdominal aortic aneurysm (AAA) and controls without AAA to assess its possible role in the pathogenesis or progression of AAA. To summarize the present evidence for an association between circulating IL-6 levels and AAA presence, we performed a meta-analysis of case-control studies that compared circulating IL-6 levels between patients with AAA and subjects without AAA. METHODS: MEDLINE and EMBASE were searched through December 2013 using Web-based search engines (PubMed and OVID). Eligible studies were case-control studies of patients with AAA and subjects without AAA reporting circulating IL-6 levels. For each study, data regarding plasma or serum IL-6 levels in both the AAA and control groups were used to generate standardized mean differences (SMDs) and 95% confidence intervals (CIs). Mixed-effects (unrestricted maximum likelihood) meta-regression analyses were performed to determine whether the differences in circulating IL-6 levels were modulated by the prespecified factors. RESULTS: Our search identified 13 eligible studies enrolling a total of 1,029 cases with AAA and 924 controls without AAA. Pooled analysis of the 13 studies demonstrated significantly greater circulating IL-6 levels in the AAA group than those in the control group (random-effects SMD 0.59; 95% CI 0.37-0.80; P for effect < 0.00001; P for heterogeneity < 0.0000). The meta-regression coefficient for the mean age (P = 0.10196) and the proportion of current smokers (P = 0.29893) was not statistically significant. That for the mean AAA diameter, however, was significantly positive (coefficient 0.02789; 95% CI 0.00778-0.04800; P = 0.00657), and that for the proportion of men was significantly negative (coefficient -0.01823; 95% CI -0.03202 to -0.00445; P = 0.00952). CONCLUSIONS: Circulating IL-6 levels are greater in patients with AAA than those in subjects without AAA, which suggest that greater circulating IL-6 levels are associated with AAA presence. As the mean AAA diameter and the proportion of men increase, circulating IL-6 levels in patients with AAA are respectively more and less greater than those in controls without AAA.

Primary ciliary dyskinesia diagnosed on nasal mucosal biopsy in two newborns.

Primary ciliary dyskinesia (PCD) is a genetic disease that causes abnormalities in ciliary structure and/or function. Ciliated cells line the upper and lower respiratory tracts and the Eustachian tube. Impairment of mucus clearance at these sites leads to sinusitis, repeated pulmonary infections, bronchiectasis, and chronic otitis media. Situs inversus occurs randomly in approximately 50% of subjects with PCD. The triad of situs inversus, bronchiectasis and sinusitis is known as Kartagener syndrome. PCD is usually an autosomal recessive disease, but occasional instances of X-linked transmission have been reported. Specific diagnosis requires examination of ciliary function or structure on light and electron microscopy. Early diagnosis and respiratory management are important in order to prevent the development of bronchiectasis and deterioration in lung function. We report early diagnosis of PCD on nasal mucosal biopsy in two newborns who presented with prolonged respiratory distress and rhinorrhea.