Use of the index of pulmonary vascular disease for predicting long-term outcome of pulmonary arterial hypertension associated with congenital heart disease

AimsLimited data exist on risk factors for the long-term outcome of pulmonary arterial hypertension (PAH) associated with congenital heart disease (CHD-PAH). We focused on the index of pulmonary vascular disease (IPVD), an assessment system for pulmonary artery pathology specimens. The IPVD classifies pulmonary vascular lesions into four categories based on severity: (1) no intimal thickening, (2) cellular thickening of the intima, (3) fibrous thickening of the intima, and (4) destruction of the tunica media, with the overall grade expressed as an additive mean of these scores. This study aimed to investigate the relationship between IPVD and the long-term outcome of CHD-PAH.MethodsThis retrospective study examined lung pathology images of 764 patients with CHD-PAH aged <20 years whose lung specimens were submitted to the Japanese Research Institute of Pulmonary Vasculature for pulmonary pathological review between 2001 and 2020. Clinical information was collected retrospectively by each attending physician. The primary endpoint was cardiovascular death.ResultsThe 5-year, 10-year, 15-year, and 20-year cardiovascular death-free survival rates for all patients were 92.0%, 90.4%, 87.3%, and 86.1%, respectively. The group with an IPVD of ≥2.0 had significantly poorer survival than the group with an IPVD <2.0 (P = .037). The Cox proportional hazards model adjusted for the presence of congenital anomaly syndromes associated with pulmonary hypertension, and age at lung biopsy showed similar results (hazard ratio 4.46; 95% confidence interval: 1.45–13.73; P = .009).ConclusionsThe IPVD scoring system is useful for predicting the long-term outcome of CHD-PAH. For patients with an IPVD of ≥2.0, treatment strategies, including choosing palliative procedures such as pulmonary artery banding to restrict pulmonary blood flow and postponement of intracardiac repair, should be more carefully considered

Characterization of Piperacillin/Tazobactam-Resistant Klebsiella oxytoca Recovered from a Nosocomial Outbreak.

We characterized 12 clinical isolates of Klebsiella oxytoca with the extended-spectrum β-lactamase (ESBL) phenotype (high minimum inhibitory concentration [MIC] values of ceftriaxone) recovered over 9 months at a university hospital in Japan. To determine the clonality of the isolates, we used pulsed-field gel electrophoresis (PFGE), multi-locus sequence typing (MLST), and PCR analyses to detect blaRBI, which encodes the β-lactamase RbiA, OXY-2-4 with overproduce-type promoter. Moreover, we performed the isoelectric focusing (IEF) of β-lactamases, and the determination of the MICs of β-lactams including piperacillin/tazobactam for 12 clinical isolates and E. coli HB101 with pKOB23, which contains blaRBI, by the agar dilution method. Finally, we performed the initial screening and phenotypic confirmatory tests for ESBLs. Each of the 12 clinical isolates had an identical PFGE pulsotype and MLST sequence type (ST9). All 12 clinical isolates harbored identical blaRBI. The IEF revealed that the clinical isolate produced only one β-lactamase. E. coli HB101 (pKOB23) and all 12 isolates demonstrated equally resistance to piperacillin/tazobactam (MICs, >128 μg/ml). The phenotypic confirmatory test after the initial screening test for ESBLs can discriminate β-lactamase RbiA-producing K. oxytoca from β-lactamase CTX-M-producing K. oxytoca. Twelve clinical isolates of K. oxytoca, which were recovered from an outbreak at one university hospital, had identical genotypes and produced β-lactamase RbiA that conferred resistance to piperacillin/tazobactam. In order to detect K. oxytoca isolates that produce RbiA to promote research concerning β-lactamase RbiA-producing K. oxytoca, the phenotypic confirmatory test after the initial screening test for ESBLs would be useful

Choroidal Neovascularization Is Inhibited in Splenic-Denervated or Splenectomized Mice with a Concomitant Decrease in Intraocular Macrophage

<div><p>Purpose</p><p>To determine the involvement of sympathetic activity in choroidal neovascularization (CNV) using laser-induced CNV in a mouse model.</p><p>Methods</p><p>We investigated changes in the proportions of intraocular lymphocytes, granulocytes, and three macrophage subtypes (Ly6C^hi, Ly6C^int, and Ly6C^lo) after laser injury in mice using flow cytometry, and evaluated CNV lesion size in mice lacking inflammatory cells. Further, we evaluated the lesion size in mice administered the β3 receptor antagonist, splenic-denervated and splenectomized mice. We also assessed changes in the proportions of intraocular macrophages and peripheral blood monocytes in splenic-denervated and splenectomized mice. Lastly, lesion size was compared between splenic-denervated mice with or without adoptive transfer of macrophages following laser injury. After Ly5.1 mice spleen-derived Ly6C^hi cells were transferred into Ly5.2 mice, the proportions of intraocular Ly5.1⁺Ly6C^hi cells were compared.</p><p>Results</p><p>In WT mice, the proportion of CD4⁺ T cells recruited into the eye increased progressively from day 3 to day 7 after laser injury, whereas, intraocular CD8⁺ T cells did not change significantly. Proportions of B220⁺ cells, granulocytes, and two subtypes of intraocular macrophages (Ly6C^hi and Ly6C^lo) peaked at day 3 following laser injury. In contrast, Ly6C^int/loCD64⁺ subtype showed a significantly higher percentage at day 7 after laser injury. There were no differences in lesion size between <i>CD4</i>^{<i>–/–</i>}or <i>Rag2</i>^{<i>–/–</i>}mice and controls, whereas lesion size was significantly reduced in <i>CCR2</i>^{<i>−/−</i>} mice and clodronate liposome-treated mice. CNV lesion area was significantly reduced in mice with β3 blocker treatment, splenic-denervated and splenectomized mice compared with controls. Intraocular Ly6C^hi macrophages were also reduced by splenic denervation or splenectomy. Adoptive transfer of spleen-derived Ly6C^hi cells increased the lesion size in splenic-denervated mice. Compared with controls, intraocular donor-derived Ly6C^hi cells recruited into the eye were reduced in splenic-denervated and splenectomized mice.</p><p>Conclusions</p><p>Although lymphocytes had little effect on CNV formation, Ly6C^hi macrophages/monocytes exacerbated CNV in mice. Sympathetic activity might contribute to CNV via the recruitment of macrophages to the eye.</p></div

Comparison of lesion size between wild-type (WT) and transgenic mice lacking lymphocytes at day 7 after laser injury.

<p>(A) There were no differences in mean choroidal neovascularization (CNV) area between WT and <i>CD4</i>^{<i>−/−</i>} mice or (B) between WT and <i>Rag2</i>^{<i>−/−</i>} mice. (C) Representative micrographs of CNV (white arrows) in RPE-choroid flatmounts. Scale bars, 100 μm. n = 8 for all groups.</p

Changes in the proportions of intraocular macrophages and peripheral blood monocytes in splenectomized mice after laser injury.

<p>(A) Less Ly6C^hi cells were recruited into the eye in splenectomized mice than those in controls both before laser treatment and at day 3 after laser injury, and intraocular Ly6C^int/loCD64⁺ cells were also reduced by splenectomy from before laser photocoagulation up to 7 days after laser, whereas, there were no significant changes in Ly6C^lo cells between two groups with or without laser injury. (B) In the peripheral blood, a lower proportion of Ly6C^int cells was observed before laser treatment, at day 3 and day 7 after laser injury, and Ly6C^lo cells were also reduced at day 7 after laser injury. In contrast, peripheral blood Ly6C^hi monocytes showed no differences between controls and splenectomized mice. All experiments were performed in triplicate. *P < 0.05 versus control of the same subtype with Dunn's multiple comparison test for post-hoc analysis.</p