Improved long-term performance of pulsatile extracorporeal left ventricular assist device

SummaryBackground and purposeThe majority of heart transplant (HTx) candidates require left ventricular assist device (LVAD) support for more than 2 years before transplantation in Japan. However, the only currently available device is the extracorporeal pulsatile LVAD. The long-term management of extracorporeal LVAD support has improved remarkably over the years. To determine which post-operative management factors are related to the long-term survival of patients on such LVAD, we retrospectively compared the incidence of complications and their management strategies between the initial and recent eras of LVAD use, classified by the year of LVAD surgery.MethodsSixty-nine consecutive patients supported by extracorporeal pulsatile LVAD as a bridge to HTx between 1994 and 2007 were reviewed retrospectively. The patients were assigned according to the time of LVAD surgery to either group A (n=30; between 1994 and 2000) or group B (n=39; between 2001 and 2007).ResultsPatients in group B survived significantly longer on LVAD support than those in group A (674.6 vs. 369.3 days; p<0.001). The 1- and 2-year survival rates were significantly higher in group B than that in group A (82% vs. 48%, p<0.0001; 68% vs. 23%, p<0.0001, respectively). The proportion of deaths due to cerebrovascular accidents was lower (17% vs. 50%, p<0.001) in group B compared with group A. The incidences of systemic infection were similar in both groups, but the proportions of patients alive and achieving transplant surgery after systemic infection were higher in group B than those in group A (55% vs. 14%, p<0.01; 14% vs. 36%, p<0.05, respectively).ConclusionsThe long-term survival of patients even on “first-generation” extracorporeal LVAD has improved significantly in the recent era. Careful management of cerebrovascular accidents and systemic infection will play important roles in the long-term LVAD management

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J-SSCG 2016)

Background and purposeThe Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J-SSCG 2016), a Japanese-specific set of clinical practice guidelines for sepsis and septic shock created jointly by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine, was first released in February 2017 and published in the Journal of JSICM, [2017; Volume 24 (supplement 2)] https://doi.org/10.3918/jsicm.24S0001 and Journal of Japanese Association for Acute Medicine [2017; Volume 28, (supplement 1)] http://onlinelibrary.wiley.com/doi/10.1002/jja2.2017.28.issue-S1/issuetoc.This abridged English edition of the J-SSCG 2016 was produced with permission from the Japanese Association of Acute Medicine and the Japanese Society for Intensive Care Medicine.MethodsMembers of the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine were selected and organized into 19 committee members and 52 working group members. The guidelines were prepared in accordance with the Medical Information Network Distribution Service (Minds) creation procedures. The Academic Guidelines Promotion Team was organized to oversee and provide academic support to the respective activities allocated to each Guideline Creation Team. To improve quality assurance and workflow transparency, a mutual peer review system was established, and discussions within each team were open to the public. Public comments were collected once after the initial formulation of a clinical question (CQ) and twice during the review of the final draft. Recommendations were determined to have been adopted after obtaining support from a two-thirds (> 66.6%) majority vote of each of the 19 committee members.ResultsA total of 87 CQs were selected among 19 clinical areas, including pediatric topics and several other important areas not covered in the first edition of the Japanese guidelines (J-SSCG 2012). The approval rate obtained through committee voting, in addition to ratings of the strengths of the recommendation, and its supporting evidence were also added to each recommendation statement. We conducted meta-analyses for 29 CQs. Thirty-seven CQs contained recommendations in the form of an expert consensus due to insufficient evidence. No recommendations were provided for five CQs.ConclusionsBased on the evidence gathered, we were able to formulate Japanese-specific clinical practice guidelines that are tailored to the Japanese context in a highly transparent manner. These guidelines can easily be used not only by specialists, but also by non-specialists, general clinicians, nurses, pharmacists, clinical engineers, and other healthcare professionals

Germ cell-intrinsic requirement for the homeodomain transcription factor PKnox1/Prep1 in adult spermatogenesis.

PKnox1 (also known as Prep1) belongs to the TALE family of homeodomain transcription factors that are critical for regulating growth and differentiation during embryonic and postnatal development in vertebrates. We demonstrate here that PKnox1 is required for adult spermatogenesis in a germ cell-intrinsic manner. Tamoxifen-mediated PKnox1 loss in the adult testes, as well as its germ cell-specific ablation, causes testis hypotrophy with germ cell apoptosis and, as a consequence, compromised spermatogenesis. In PKnox1-deficient testes, spermatogenesis was arrested at the c-Kit+ spermatogonia stage, with a complete loss of the meiotic spermatocytes, and was accompanied by compromised differentiation of the c-Kit+ spermatogonia. Taken together, these results indicate that PKnox1 is a critical regulator of maintenance and subsequent differentiation of the c-Kit+ stage of spermatogonia in the adult testes

Germ cell-specific PKnox1 loss causes defective spermatogenesis.

<p>The size (<b>A</b>) and weight (<b>B</b>) of testes from 12-week-old PKnox1-GKO and control mice. Bars are the mean and standard deviation of the weight of testes. (n = 4 for each genotype). Tissue sections from control and GKO epididymis stained with H&E (<b>C</b>, <b>D</b>) and testes stained with H&E (<b>E, F</b>), TUNEL (<b>G, H</b>) and anti-SCP3 antibody with DAPI (<b>I, J</b>). Data are representative of 4 independent experiments. Scale bars, 50 μm.</p

Loss of PKnox1 affects PCNA expression in c-Kit⁺ spermatogonia.

<p>Tissue sections from the testis from 12-week-old PKnox1-GKO and control mice were double stained with the indicated antibody combinations and counterstained with DAPI. Arrows indicate GFRα1⁺ and c-Kit⁺ cells with or without PCNA expression. Broken lines indicate the basement membrane of seminiferous tubules. Data are representative of 3 independent experiments. Scale bars, 25 μm.</p

PLZF and c-Kit are expressed in a distinct subset of spermatogonia in PKnox1-deficient testes.

<p>Immunohistochemical analysis of PLZF (<b>A, D</b>) and c-Kit (<b>B, E</b>) expression in the testis from 12-week-old PKnox1-GKO and control mice with merged images (<b>C</b>, <b>F</b>). Tissue sections were double stained with the indicated combinations of antibodies and counterstained with DAPI. Arrowheads and arrows indicate PLZF⁺ and c-Kit⁺ cells, respectively. Broken lines indicate the basement membrane of seminiferous tubules. Data are representative of 3 independent experiments. Scale bars, 50 μm.</p

Loss of PKnox1 in the adult testis causes defective spermatogenesis.

<p>The size (<b>A</b>) and weight (<b>B</b>) of adult testes from 12-week-old PKnox1-CKO and control mice 3 weeks after induction of <i>PKnox1</i> deletion. Bars are the mean and standard deviation of the weight of testes. (n = 4 for each genotype). Tissue sections from control and CKO epididymis stained with H&E (<b>C</b>, <b>D</b>) and testes stained with H&E (<b>E, F</b>), TUNEL (<b>G, H</b>) and anti-SCP3 antibody with DAPI (<b>I, J</b>). Data are representative of 4 independent experiments. Scale bars, 50 μm.</p

Loss of PKnox1 causes accumulation of GFRα1⁺ cells and differentiation arrest of c-Kit⁺ spermatogonia.

<p>Whole-mount immunodetection of cells expressing GFRα1 (red) and c-Kit (green) in seminiferous tubules of 12-week-old littermate controls (<b>A, C, C’, E, G and G’</b>), PKnox1-GKO (<b>B, D</b>), and -CKO mice (<b>F, H</b>). A_s; single cell, A_pr; paired cells, A_al; aligned cells. Data are representative of 3 independent experiments. Scale bars, 50μm.</p

Expression of PKnox1 in postnatal testes.

<p>(<b>A</b>) Expression of <i>PKnox1</i> and <i>β-actin</i> (control) mRNA transcripts in testes at postnatal (P) days 6, 14, 35 and 6 months obtained from wild-type mice and 12-week-old <i>W/Wv</i> mice. (<b>B-E</b>) Immunohistochemical analysis to localize PKnox1-expressing cells in the adult testis. Serial tissue sections of the testes from 8-week-old wild-type mice were stained with a PKnox1-specific antibody, in combination with anti-c-Kit (<b>B</b>, <b>C</b>) or PLZF antibodies (<b>D</b>, <b>E</b>). Inserts indicate cells co-expressing both Prep1 and c-Kit or PLZF. Asterisks indicate haploid cells positive for PKnox1. Data are representative of 3 independent experiments. Scale bar, 50 μm.</p