Polymorphisms in the ficolin 1 gene (FCN1) are associated with susceptibility to the development of rheumatoid arthritis

Objectives. We investigated the possible association of rheumatoid arthritis (RA) with single nucleotide polymorphisms (SNP) within the ficolin (FCN) genes. Two SNPs in the FCN1 gene, four SNPs in the FCN2 gene and one SNP in the FCN3 gene were studied. Methods. The SNPs within the FCN genes were detected by an experimental INNO-LiPA methodology (Innogenetics, Belgium) in a population consisting of 338 RA patients and 595 controls. The significant SNPs were further evaluated in two subpopulations and related to carriage of the human leukocyte antigen-shared epitope (HLA-SE), rheumatoid factor (RF) and the presence of anti-citrullinated protein/peptide antibodies (ACPA). Results. Two SNPs in the FCN1 gene were significantly associated with RA: the A allele rs2989727 was significantly increased in RA patients (67%) compared with controls (60%) (P = 0.002). Also, the frequency of the G allele of rs1071583 was increased in RA patients (68%) compared with controls (61%) (P = 0.003). Analysis of agreement between SNPs suggested strong linkage between rs2989727 and rs1071583. Carriage of a FCN1 SNP was independent of carriage of the HLA-SE, RF status and ACPA positivity. Conclusions. We describe two linked SNPs in the FCN1 gene that are associated with the development of RA

Chronic kidney disease progression is mainly associated with non-recovery of acute kidney injury

Background: Identifying individuals who are at increased risk for accelerated progressive chronic kidney disease (CKD) and who might benefit from preventive interventions is an important challenge. Methods: The present observational study evaluated the effect of an episode of Acute Kidney Injury (AKI) on the evolution of the renal trajectory in a cohort of 311 ambulatory CKD patients. We analyzed the evolution of eGFR in this cohort within a 5-year time window around an AKI episode. The mean of the available eGFR-values over a 6 month period was calculated once at the start and once at the end of the 5-year period. Slow and fast CKD progression were defined as a decrease by respectively 1 category of 15 ml/min/1.73 m(2) over the 5-year time window. The influence of AKI on progression status was analyzed. Results: Median eGFR decline over the 5 year period was 11, 22 and 6 ml/min/1.73 m(2) in the total, AKI and no AKI group respectively. AKI occurred in 44/72 versus 50/239 of fast versus slow progressors (odds ratio: 5.9, 95 % confidence interval: 3.4-10.5). An incomplete recovery of eGFR after an AKI episode (median in overall, fast progressors, slow progressors 11, 20 and 4 ml/min/1.73 m(2) respectively) was the major component for the overall loss of renal function over the 5-year window. Our data failed to provide evidence that the CKD progression became more accelerated once kidney function was stabilized after the AKI episode. Conclusions: Incomplete recovery of AKI was related with accelerated CKD-progression. Episodes of AKI were not associated with an accelerated decline of kidney function once the AKI episode had resolved. In the group without AKI episode, the progression was similar to that of the general population without CKD

Which sevoflurane wash-in rates towards 1.0 MAC ensure adequate anesthetic depth after a standardized intravenous induction before surgical incision?

Background: After intravenous (IV) induction of anesthesia, inhaled agent wash-in has to be titrated in such a manner that the combined effects of this agent and remaining opioid and propofol continue to ensure loss of consciousness (LOC) prior to incision. We assessed the effect of different sevoflurane wash-in rates on anesthetic depth. Methods: Anesthesia was induced with sufentanil (0.2 mu g/kg), followed 4 min later by propofol (1-2 mg/kg, depending on age), and rocuronium (0.6 mg/kg) in 33 ASA PS I-III patients. After tracheal intubation, sevoflurane wash-in towards 1 age-adjusted minimal alveolar concentration (MAC) was controlled to occur exponentially with a time constant of 2.5, 5.0, or 11.1 min, depending on the anticipated time of incision: FAST, MEDIUM, or SLOW, respectively. The effect-site MAC (MACe), sufentanil effect site concentration (CeSuf), Noxious Stimulation Response Index, Bispectral Index (BIS), and Brice questionnaire defined 3 probabilities of LOC (PLOC): extremely high, i.e. MACe > 0.63 and CeSuf > 0.17 ng/mL or NSRI 65; and insufficient, i.e. NSRI > 50 and BIS > 65 or recall elicited by the Brice questionnaire. Results: The end-expired sevoflurane concentration rose towards 1 MAC with a time constant (95% con-fidence interval) of 2.6 (2.6; 2.7), 5.7 (5.3; 6.2), and 10.9 (9.6; 12.6) min in groups FAST, MEDIUM, and SLOW, respectively. 0.63 MACe was reached at 9.8 [9.8; 9.8], 12.3 [12.3; 12.6], and 18.5 [18.3; 18.7] min (median and interquartile range), for groups FAST, MEDIUM, and SLOW, respectively, with CeSuf > 0.17 ng/mL at the moment 0.63 MACe was reached in all but 2 patients in group SLOW. Before reaching 0.63 MACe, PLOC was high to extremely high in group FAST and MEDIUM patients, but insufficient in group SLOW, even though the modified Brice questionnaire did not elicit any recall. Conclusion: An exponential end-expired sevoflu-rane wash-in rate towards 1.0 MAC with a time constant = 10.9 min ensures hypnosis after IV induction with propofol (1-2 mg/kg), preceded 4 min earlier by sufentanil (0.2 mu g/kg). Integrating these patterns into automated low-flow target controlled algorithms may help optimize anesthetic agent delivery

Monitoring the risk for a “valley of inadequate anesthesia” using bispectral index and the noxious stimulation response index during different inflow speeds of sevoflurane.

Title: Monitoring the risk for a “valley of inadequate anesthesia” using bispectral index and the noxious stimulation response index during different inflow speeds of sevoflurane. Authors: Mira Van Thielen MD1 2, Rik Carette MD1 , Jan F.A. Hendrickx MD, PhD1 2 , Andre M. De Wolf MD, PhD3 , Hugo E.M. Vereecke MD, PhD4 5 Affilliations: 1 OLV Hospital, Aalst, Belgium; 2 Ghent University, Ghent, Belgium; 3 Northwestern University, Chicago, USA; 4 AZ Sint-Jan Brugge-Oostende AV, Brugge, Belgium; 5 University Medical Center Groningen and University of Groningen, Groningen, The Netherlands Abstract Introduction: The “valley of inadequate anesthesia” refers to an increased risk for awareness, movement or hemodynamic instability evoked by an insufficient inflow of volatile agents to compensate for the gradual elimination of intravenously administered boluses of induction agents. The combined drug effects of volatile and intravenous drugs should ensure a sufficient hypnotic drug effect and immobility (as respectively quantified by bispectral index (BIS, Medtronic) and the noxious stimulation response index (NSRI, Dräger)), while maintaining stability in arterial blood pressure (ABP) and heart rate (HR). NSRI is a derivative of the probability of tolerance of laryngoscopy, as estimated by Hannivoort et al. for most combinations of propofol, opioids and volatile agents.1 NSRI of 20 equals an estimated probability of immobility in response to laryngoscopy of 90%. We compare the time course of BIS, NSRI, ABP and HR after a bolus of propofol and sufentanil, followed by three different inflow speeds of sevoflurane. We hypothesize that BIS and NSRI should stay below 60 and 20, respectively, at all times between the start of sevoflurane and reaching a target of 1.0 MAC. We also compare ABP and HR between groups. Methods: 33 ASA score I-III patients (age range: 27-86 years; BMI range 22-34 kg/m2 ) presenting for abdominal surgery received sufentanil (0.2 µg/kg) and propofol (1 or 2 mg/kg, depending on age) followed by intubation of the trachea, 2.5 min after loss of responsiveness and rocuronium (0.6 mg/kg). Sevoflurane was administered (after randomization) in a ‘slow’(n = 9), ‘medium’(n = 8), and ‘fast’(n = 9) group; defined by a time constant of respectively 10.9, 5.7, and 2.6 min wash-in time towards 1.0 MAC. These inflow speeds are similar to those used in a commercialized automatic controller of the inflow of volatile agents (Flow-I, Maquet). BIS and NSRI were blinded to the anesthesiologist. For all measures, the 95% confidence interval (CI 95%) of the difference of means was calculated at one minute intervals between minutes 0 to 25 after propofol (p < 0.05 if zero is outside 95% CI). An escape bolus of sufentanil (0.1 µg/kg) was allowed per protocol (and included in the NSRI calculations) to counter movement, tachycardia or hypertension indicating insufficient anesthesia at any time. Results and discussion: Extra sufentanil was needed in all groups, for movement (1 in slow, 1 in medium, 1 in fast), for tachycardia (1 in slow, 1 in medium and 1 in fast), and for hypertension (3 in medium, 2 in fast). Figure 1 shows the time course of BIS, NSRI, HR and MAP. All groups included cases with BIS > 60 and/or NSRI > 20 (n in slow > medium > fast). High BIS and NSRI were not always consistent. Figure 2 shows similar BIS and NSRI during the first 8 minutes in all groups, confirming equipotency for these measures till the start of sevoflurane. Mean NSRI differs between slow and medium, slow and fast and medium and fast (respectively from minute 10 to 18, 10 to 20 and 10 to 14) evoked by the deliberate differences in inflow speed of sevoflurane. Mean BIS differs between slow and medium and slow and fast (respectively from minute 15 to 16 and 11 to 24). Heart rate and blood pressure did not differ between groups. A Brice questionnaire found no cases of explicit recall. Conclusion: After a bolus dose of propofol, sufentanil, and rocuronium, both BIS>60 and NSRI>20 warn the anesthesiologist for an increased risk of a “valley of inadequate anesthesia”. ABP and HR don’t identify differences in drug potency between groups. A higher initial dose of sufentanil (e.g. 0,3 µg/kg) might reduce the need for escape treatment. Reference 1. Hannivoort LN, et al., Br J Anaesth. 2016 May;116(5):624-31