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Table 9 Experimental conduct and exclusion criteria of lymphocyte apoptosis studies

From: Uncontrolled sepsis: a systematic review of translational immunology studies in intensive care medicine

Author Study population Sample timing Definition of sepsis Microbiology results provided Independent adjudication of sepsis diagnosis Exclusion criteria immunosuppressive disease Exclusion criteria malignancy Primary conclusion of study (in relation to lymphocyte apoptosis)
Time of first sample No. samples (time span)
Roger [43] Sepsis Before first abs 1 3 B C Y Y Y Y Concomitant T cell proliferation and T cell apoptosis are observed in human sepsis
Bandyopadhyay [58] Trauma ? Every 4 days (28 days) N N N Y N CD47 triggering, SHP-1 mediated NFkB suppression and elevated TRAIL levels increase…T cell apoptosis
White [11] Sepsis 24 h (ICU adm/positive BC) 2 (7 days) 1 B C N Y Y N Patients with infection and sepsis have deficient IL-2 and IL-7 gene expression
White [11] Elective surgery (infective complications) Pre-insult 3 (5 days) 4 N Y Y N  
Zhang [44] Sepsis 24 h (sep shock) 1 1C N N Y N The expression of PD-1 on T cells [is] up regulated in septic shock
Guignant [45] Sepsis 48 h (sep shock) 3 (10 days) 1C Y Y N Y PD-1 related molecules may constitute a novel immunoregulatory system involved in sepsis-induced immune alterations
Vaki [46] Sepsis 12 h (organ failure)   2 B C Y Y Y N These findings support…the existence of an early circulating factor in severe sepsis/shock, modulating apoptosis of CD4 lymphocytes
Slotwinski [62] Elective surgery Pre-insult 4 (7 days) N N N Y N Preoperative enteral immunonutrition prevents postoperative decrease in lymphocyte subsets
Gogos [47] Sepsis 24 h (signs of sepsis) 1 2 B C Y Y Y N Major differences of the early statuses of innate and adaptive immune systems exist between sepsis and severe sepsis/shock in relation the underlying type of infection
Hoogerwerf [48] Sepsis 24 h (dx sepsis) 1 2 A Y Y Y N In patients with sepsis, alterations in apoptosis of circulating leukocytes occur in a cell-specific manner
Yousef [49] Sepsis ? 1 1 A B C N N Y N Percentage of apoptotic lymphocyte median values [could be] an indicator of prognosis and survival in critically ill patients
Turrel-Davin [50] Sepsis 48 h (sep shock) 2 (5 days) 1C Y Y N N Pro-apoptotic genes BID and FAS appear to constitute promising apoptosis markers
Pelekanou [51] Sepsis 24 h (signs of sepsis) 1 1 2 A B C Y Y Y N Decrease of CD-4 lymphocytes…is characteristic of sepsis arising in ventilator associated pneumonia
Papadima [61] Elective surgery Pre-insult 2 (1 day) N -   Y Y No alterations in lymphocyte counts [and] subpopulations [following use of epidural anaesthesia]
Delogu [52] Sepsis 24 h (sep shock) 1 ? C Y N N N Blood caspase-1 elevated in sepsis. IL-6 correlates with apoptotic rate and caspase-9 expression in lymphocytes
Weber [53] Sepsis 4 h (sev sepsis) 1 1 B N N Y Y In early severe sepsis…induction of…Bim,Bid,Bak and downregulation of Bcl-2 and Bcl-xl is observed
Roth [54] Sepsis ? 1 1 A B C N N N N These findings strongly suggest that in septic patients Th1 T cells are selectively susceptible to apoptosis
Le Tulzo [55] Sepsis +ve microbiology ±3 days 2 (6 days) 1 B C E Y N N N Lymphocyte apoptosis is rapidly increased in…septic shock…and leads to a profound and persistent lymphopaenia associated with poor outcome
Hotchkiss [56] Sepsis 6 h (death) 1 6 Y N Y N Capsase 9 mediates profound progressive loss of B and CD4 T helper cells in [severe] sepsis
Delogu [63] Elective surgery Pre-insult 3 (4 days) N N N Y Y Surgical trauma is associated with a significant but transient increase in lymphocyte commitment to apoptosis
Pellegrini [59] Trauma ? 2/week (until death/discharge) N N N N N Increased levels of apoptosis are not directly associated with negative trauma patient outcome
Delogu [64] Surgical Pre-insult 3 (4 days) N N N Y Y Surgical trauma upregulates lymphocyte death signalling factors and downregulates survival factors. Increased apoptosis of CD8+ cells maybe associated with greater risk of postsurgical infection
Hotchkiss [60] Trauma 10 h (injury to surgery) 1 N N N N N Focal apoptosis of intestinal epithelial and lymphoid tissues occurs extremely rapidly after injury
Hotchkiss [57] Sepsis 6 h (death) 1 6 Y Y N N Caspase-3 mediated apoptosis causes extensive lymphocyte apoptosis in sepsis
Sasajima [65] Elective surgery Pre-insult 5 (7 days) N N N N N Transient T cell apoptosis occurs after major operations
Sugimoto [66] Elective surgery Pre-insult 4 (4 days) N N N N N Enhanced FasL expression is likely to be related to systemic inflammatory responses induced during the perioperative period
  1. Sample timing: Were control samples taken at the same time point after the inflammatory stimulus as subject samples? When was the first sample taken from the subject? How many samples were taken for each subject in total and over what time span? Sepsis criteria: The criteria used to enrol subjects into the study. Where subgroups of these criteria were used (e.g. septic shock) these are detailed. 0, not stated; 1, ACCP/SCCM 1992 Consensus Conference [73]; 2, ACCP/SCCM Consensus Conference 2001 [74]; 3, SSC Consensus Conference 2008 [75]; 4, CDC NNIC [86]; 5, Microbiology and clinical assessment; 6, Postmortem identification of infection; N, infection not considered; question mark (?), criteria not described. Sepsis severity groups enrolled: A = sepsis, B = severe sepsis, C = septic shock, D = acute renal failure, E = SIRS. Microbiology documentation: Were causative organisms clearly isolated and identified? Were additional steps taken to define whether the subject had sepsis beyond the initial clinical diagnosis, i.e. retrospective review of the case in light of subsequent information?