scholarly journals S100A9 Links Inflammation and Repair in Myocardial Infarction

2020 ◽  
Vol 127 (5) ◽  
pp. 664-676 ◽  
Author(s):  
Goran Marinković ◽  
Duco Steven Koenis ◽  
Lisa de Camp ◽  
Robert Jablonowski ◽  
Naomi Graber ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Function ◽  
Therapeutic Window ◽  
Term Therapy ◽  
Short Term ◽  
Hematopoietic Stem ◽  
Beneficial Effects ◽  
Inflammatory Phase ◽  
Short Term Therapy

Rationale: The alarmin S100A9 has been identified as a potential therapeutic target in myocardial infarction. Short-term S100A9 blockade during the inflammatory phase post-myocardial infarction inhibits systemic and cardiac inflammation and improves cardiac function long term. Objective: To evaluate the impact of S100A9 blockade on postischemic cardiac repair. Methods and Results: We assessed cardiac function, hematopoietic response, and myeloid phagocyte dynamics in WT (wild type) C57BL/6 mice with permanent coronary artery ligation, treated with the specific S100A9 blocker ABR-238901 for 7 or 21 days. In contrast to the beneficial effects of short-term therapy, extended S100A9 blockade led to progressive deterioration of cardiac function and left ventricle dilation. The treatment reduced the proliferation of Lin − Sca-1 + c-Kit + hematopoietic stem and progenitor cells in the bone marrow and the production of proreparatory CD150 + CD48 − CCR2 + hematopoietic stem cells. Monocyte trafficking from the spleen to the myocardium and subsequent phenotype switching to reparatory Ly6C lo MerTK hi macrophages was also impaired, leading to inefficient efferocytosis, accumulation of apoptotic cardiomyocytes, and a larger myocardial scar. The transcription factor Nur77 (Nr4a1 [nuclear receptor subfamily 4 group A member 1]) mediates the transition from inflammatory Ly6C hi monocytes to reparatory Ly6C lo macrophages. S100A9 upregulated the levels and activity of Nur77 in monocytes and macrophages in vitro and in Ly6C hi/int monocytes in vivo, and S100A9 blockade antagonized these effects. Finally, the presence of reparatory macrophages in the myocardium was also impaired in S100A9 −/ − mice with permanent myocardial ischemia, leading to depressed cardiac function long term. Conclusions: We show that S100A9 plays an important role in both the inflammatory and the reparatory immune responses to myocardial infarction. Long-term S100A9 blockade negatively impacts cardiac recovery and counterbalances the beneficial effects of short-term therapy. These results define a therapeutic window targeting the inflammatory phase for optimal effects of S100A9 blockade as potential immunomodulatory treatment in acute myocardial infarction.

Time—A Neglected Aspect of Psychiatric Treatments

1978 ◽  
Vol 12 (4) ◽  
pp. 291-295
Author(s):  
O. T. Stanley
Keyword(s):  
Treatment Outcome ◽  
Special Reference ◽  
Latency Period ◽  
Term Therapy ◽  
Psychological Processes ◽  
Short Term ◽  
Therapeutic Implications ◽  
Short Term Therapy ◽  
Difficult Issue

This review attempts to deal with the complex issues involved in the time to heal, with special reference to psychological processes. The questions of convalescence and relapse in organic medicine are explored and extrapolated to psychiatric processes. The concept of a latency period of change in treatment outcome is discussed with reference to both less complicated reactive states as well as highly charged neurotic processes. The problems of recognizing slow but perceptible change and separating it from failure to respond is analysed. The value of long-term psychotherapy is assessed and comparison made with the newer concept of short-term therapy. Crisis therapy and disaster reactions are discussed within the concept of time to heal. Finally the difficult issue of “miraculous cure” with its therapeutic implications is evaluated.

scholarly journals Ambulatory Intravenous Antibiotic Therapy in Quebec: The Hôpital Charles LeMoyne Experience in 1996

2000 ◽  
Vol 11 (suppl a) ◽  
pp. 6A-10A
Author(s):  
Laurent Delorme ◽  
Charles Frenette ◽  
Isabelle Le Corre ◽  
Julie Duchesne ◽  
Carole Delorme ◽  
...  
Keyword(s):  
Antibiotic Therapy ◽  
Term Therapy ◽  
Outpatient Therapy ◽  
Short Term ◽  
Intravenous Antibiotic ◽  
Therapy Program ◽  
Intravenous Antibiotic Therapy ◽  
Short Term Therapy ◽  
Long Term Therapy

From January 1, 1996 to December 31, 1996, 343 patients received outpatient intravenous antibiotic therapy at Charles LeMoyne Hospital, a 436-bed, acute care hospital in Greenfield Park, south of Montréal, Québec. The infectious diseases department saved 2660 bed-days using outpatient therapy. The mean duration of outpatient therapy was 7.76 days; 81.6% of patients were admitted to the program directly from the emergency room, or outpatient hospital clinics or private offices in the community. Hospitalized patients constituted only 18.4% of admissions to the outpatient intravenous antibiotic therapy program. Forty per cent of the surgical/medical staff participated in the program and they were able to generate a significant impact by diverting patients to outpatient therapy. Two types of patients can benefit from an outpatient intravenous antibiotic therapy program. One group of patients needs empirical short term therapy and can be switched to oral sequential therapy after two to five days of outpatient intravenous antibiotic therapy. A second group of patients needs specific long term therapy for the full duration of the antibiotic therapy. Empirical short term therapy can be managed by emergency department or hospital-based primary physicians, or medical/surgical specialists. Specific long term therapy can be managed by microbiology/infectious disease specialists or medical/surgical specialists. Hospitals that want to relieve pressure on emergency rooms and hospital bed demands should create facilities for both types of patients. Cefazolin and gentamicine/tobramycine were the most commonly used antibiotics in empirical short term therapy and in terms of number of patients treated. Ceftriaxone and vancomycin were most commonly used for long term therapy. The Drug acquisition antibiotic cost was $73,117 but constituted only 20% of the total outpatient intravenous antibiotic therapy cost. The per diem ambulatory cost was $140/patient/day.

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