Non-random distribution of deleterious mutations in the DNA and protein-binding domains of IRF6 are associated with Van Der Woude syndrome

Background: The development of the face occurs during the early days of intrauterine life by the formation of facial processes from the first Pharyngeal arch. Derangement in these well-organized fusion events results in Orofacial clefts (OFC). Van der Woude syndrome (VWS) is one of the most common causes of syndromic cleft lip and/or palate accounting for 2% of all cases. Mutations in the IRF6 gene account for 70% of cases with the majority of these mutations located in the DNA-binding (exon 3, 4) or protein-binding domains (exon 7-9). The current study was designed to update the list of IRF6 variants reported for VWS by compiling all the published mutations from 2013 to date as well as including the previously unreported VWS cases from Africa and Puerto Rico.Methods: We used PubMed with the search terms; "Van der Woude syndrome," "Popliteal pterygium syndrome," "IRF6," and "Orofacial cleft" to identify eligible studies. We compiled the CADD score for all the mutations to determine the percentage of deleterious variants.Results: Twenty-one new mutations were identified from nine papers. The majority of these mutations were in exon 4. Mutations in exon 3 and 4 had CADD scores between 20 and 30 and mutations in exon 7-9 had CADD scores between 30 and 40. The presence of higher CADD scores in the protein-binding domain (exon 7-9) further confirms the crucial role played by this domain in the function of IRF6. In the new cases, we identified five IRF6 mutations, three novel missense mutations (p.Phe36Tyr, p.Lys109Thr, and p.Gln438Leu), and two previously reported nonsense mutations (p.Ser424*and p.Arg250*).Conclusion: Mutations in the protein and DNA-binding domains of IRF6 ranked among the top 0.1% and 1% most deleterious genetic mutations, respectively. Overall, these findings expand the range of VWS mutations and are important for diagnostic and counseling purposes.</p

A comparison of the effect of two doses of propofol with sodium thiopentone in the prevention of suxamethonium induced fasciculation and myalgia

Background: The use of suxamethonium commonly results in fasciculation and myalgia. This could be distressing to the patient. We compared the efficacy of high dose propofol, 3.5mg/kg with standard dose propofol, 2mg/kg and thiopentone sodium, 5mg/kg in reducing the suxamethonium induced fasciculation and myalgia.Methods: A prospective double blind randomized study in 105 unpremedicated, ASA l or II patients, scheduled for elective general anaesthesia. They were randomized, and induced with propofol, 2mg/kg (Group P), thiopentone, 5mg/kg (Group STP) or high dose propofol, 3.5mg/kg (Group HP). Tracheal intubation was facilitated with IV suxamethonium (1mg/kg). The incidence and severity of fasciculation, 24 hours postoperative myalgia and creatine phosphokinase (CPK) levels were recorded.Results: The incidence (p &lt; 0.001) and severity (p =0.034) of fasciculation was significantly lower in Group HP than Groups P and STP. The incidence (p &lt;0.001), and severity (p =0.010)of myalgia followed a similar trend. The mean 24hours postoperative CPK level was significantly lower in Group HP than Groups P and STP, p &lt;0.001.Conclusion: It is concluded that high dose propofol is more efficient than standard dose propofol and thiopentone in minimizing suxamethonium-induced fasciculation and myalgia. Key Words: suxamethonium, myalgia, fasciculation, creatinine kinase, propofol, sodium thiopenton

Evaluation of the accuracy of the masimo pronto compared to laboratory spectrophotometric method of intraoperative haemoglobin measurement

Background: Transfusion decisions intra-operatively are generally guided by accurate blood loss estimation and intermittent invasive haemoglobin measurement. We investigated the accuracy of non- invasive intraoperative haemoglobin measurement using the Masimo Pronto (SpHb) as compared to laboratory spectrophotometry (tHb). Methods and Materials: This was a cross sectional study of 110 adult patients undergoing surgery with a potential for blood loss of 500 ml and over under general anaesthesia. Haemoglobin level was determined simultaneously postinduction, pre-transfusion and postoperatively using (SpHb) readings from Masimo Pronto® Pulse CO-Oximeter (Rainbow® SET® Technology Masimo Corporation, Irvine, CA) and haemoglobin analyzer with laboratory spectrophotometry (tHb). Results: A total of 244 sample pairs were analysed; 110 postinduction, 24 pre-transfusion and 110 post-operatively. There was a significant difference in mean haemoglobin between SpHb and tHb during the study at all time periods, p&lt;0.0001. The overall mean haemoglobin was SpHb 12.02 ±1.86 g/dl, and tHb10.49 ±1.92 g/dl, p&lt;0.0001, bias (1.5 ±1.76 g/dl), and limits of agreement-1.9 to 5.0 g/dl. There was moderate Pearson correlation (0.57) between SpHb and tHb measurements. The mean pre-transfusion haemoglobin was SpHb 10.25 ±1.96 g/dl, and tHb 8.26 ±1.27 g/dl, p&lt;0.0001, bias, 2.0 ±1.89 g/dl and limits of agreement, -1.7 to 5.7 g/dl. Conclusion: It is concluded that SpHb overestimated haemoglobin measurement as compared with tHb. Hence the Masimo Pronto was found to be inaccurate as compared with laboratory spectrophotometry in intraoperative haemoglobin measurement. The bias was too large and limits of agreement too wide between SpHb and tHb to make appropriate transfusion decisions. Keywords: Haemoglobin, invasive, non-invasive, transfusion, intraoperativ

Does the anesthetic technique influence the epinephrine and norepinephrine concentration during pelvic surgery?

Background: Epinephrine and norepinephrine concentrations increase by up to ten-fold immediately after surgical injury depending on the severity of the injury. However, the plasma levels of epinephrine and norepinephrine do not necessarily increase concurrently. The plasma epinephrine levels increase for about 48 h, while the norepinephrine levels remain elevated for about 8-10 days after injury. The choice of anesthesia has been shown to influence the secretion of epinephrine and norepinephrine. Materials and Methods: We compared the effects of balanced combined spinal-epidural anesthesia (CSEA, n = 20) and general anesthesia relaxant (GAR, n = 20) on epinephrine and norepinephrine concentrations during major pelvic surgery in patients with uterine mass > 20 weeks gestation. Blood samples for epinephrine and norepinephrine were analyzed at preinduction and 1, 3, and 4 h after surgical incision using enzyme-linked immunosorbent assay technique. Results: The mean norepinephrine concentration differs significantly after incision; at 1 h, CSEA 230.11 ± 42.85 versus GAR 51.25 ± 29.15 pg/ml, P = 0.015; and at 3 h, CSEA 116.22 ± 39.91 versus GAR 27.00 ± 19.89 pg/ml, P = 0.045. The norepinephrine concentrations increased from preinduction values after incision; at 1 h, increased in CSEA by +168% but increased in GAR by +31.7%; at 3 h, increased in CSEA by +35.64% but decreased in GAR by -22.85%; while at 4 h, decreased in CSEA by −3.37% but increased in GAR by +38.94% , P = 0.04 [Figure 2]. The mean epinephrine was comparable during the study, P > 0.05, while the mean heart rate, mean arterial blood pressure, and estimated blood loss were significantly lower with CSEA. Conclusion: We have demonstrated that in patients with uterine mass >20 weeks gestation, CSEA when compared to general anesthesia resulted in an initial increase in mean norepinephrine concentration 1 h after surgical incision followed by gradual decrease toward preinduction values

EMLA Cream vs 10% Lidocaine Cream for Attenuating Venous Cannulation Pain – A Clinical Trial

Background: Venous cannulation is a painful procedure that is associated with anxiety, distress and discomfort. But pain is frequently overlooked in adults. Aims and Objective: We compared the efficacy of 5% EMLA cream and 10% lidocaine cream in attenuating pain associated with peripheral venous cannulation. Methods: This prospective, randomized, placebo-controlled trial was conducted in 102 ASA I and II adults scheduled for elective surgery. They were randomly allocated by blind balloting to one of three groups: group E had 1.5 mL of EMLA cream, group L 1.5 mL of 10% lidocaine cream, and group P 1.5 mL KY gel. All cream was applied over a visible vein for 60 min with occlusive dressing. Pain was evaluated using visual analogue scale (VAS) and verbal rating scale (VRS). Results: The mean VAS score was significantly lower with either EMLA cream (2.62±1.76 cm) or 10% lidocaine cream (1.85±1.58 cm) than with placebo (4.78 ±1.88 cm), p<0.001. Most patients who received EMLA cream (76.5%) or 10% lidocaine cream (70.6%) compared with placebo (55.9%) had mild pain during cannulation using VRS. Conclusion: The eutectic mixture of local anesthetic cream and lidocaine cream attenuated pain associated with peripheral venous cannulation to varying degrees

Epidemiology and outcomes of hospital-acquired bloodstream infections in intensive care unit patients: the EUROBACT-2 international cohort study

Purpose In the critically ill, hospital-acquired bloodstream infections (HA-BSI) are associated with significant mortality. Granular data are required for optimizing management, and developing guidelines and clinical trials. Methods We carried out a prospective international cohort study of adult patients (≥ 18 years of age) with HA-BSI treated in intensive care units (ICUs) between June 2019 and February 2021. Results 2600 patients from 333 ICUs in 52 countries were included. 78% HA-BSI were ICU-acquired. Median Sequential Organ Failure Assessment (SOFA) score was 8 [IQR 5; 11] at HA-BSI diagnosis. Most frequent sources of infection included pneumonia (26.7%) and intravascular catheters (26.4%). Most frequent pathogens were Gram-negative bacteria (59.0%), predominantly Klebsiella spp. (27.9%), Acinetobacter spp. (20.3%), Escherichia coli (15.8%), and Pseudomonas spp. (14.3%). Carbapenem resistance was present in 37.8%, 84.6%, 7.4%, and 33.2%, respectively. Difficult-to-treat resistance (DTR) was present in 23.5% and pan-drug resistance in 1.5%. Antimicrobial therapy was deemed adequate within 24 h for 51.5%. Antimicrobial resistance was associated with longer delays to adequate antimicrobial therapy. Source control was needed in 52.5% but not achieved in 18.2%. Mortality was 37.1%, and only 16.1% had been discharged alive from hospital by day-28. Conclusions HA-BSI was frequently caused by Gram-negative, carbapenem-resistant and DTR pathogens. Antimicrobial resistance led to delays in adequate antimicrobial therapy. Mortality was high, and at day-28 only a minority of the patients were discharged alive from the hospital. Prevention of antimicrobial resistance and focusing on adequate antimicrobial therapy and source control are important to optimize patient management and outcomes