The Diagnostic Accuracy of EXTEM and HEPTEM Clotting Times Versus Standard Laboratory Tests in Cardiac Surgical Patients With and Without Normal FIBTEM Values.

OBJECTIVES: There is extensive evidence to support the use of FIBTEM to identify hypofibrinogenemia during cardiac surgery, but less to support the use of EXTEM and INTEM clotting times (CTs) to identify other plasmatic coagulation factor deficiencies. The aim of the current study was to assess the diagnostic accuracy of EXTEM, INTEM, and HEPTEM CTs, using laboratory international normalized ratio (INR) and activated partial thromboplastin time (aPTT) as reference standards. DESIGN: This was a retrospective diagnostic accuracy study. SETTING: The work took place at a tertiary referral hospital. PARTICIPANTS: A total of 176 cardiac surgical patients were enrolled. INTERVENTIONS: INR, aPTT, ROTEM EXTEM, INTEM, and HEPTEM were measured post-heparin reversal after cardiopulmonary bypass. MEASUREMENTS AND MAIN RESULTS: Sensitivity, specificity, and positive (PPVs) and negative predictive values (NPVs) for EXTEM CT >80 seconds and HEPTEM CT >280 seconds to detect INR ≥2.0, and INTEM CT >205 seconds to detect aPTT ≥38.5 seconds were calculated for all patients and the subset with normal FIBTEM A5 (>6 mm). The prevalence of INR ≥2.0 was 13%. EXTEM CT >80 seconds had a sensitivity of 1.00, specificity of 0.25, PPV of 0.17, and NPV of 1.00. HEPTEM CT >280 seconds had a sensitivity of 0.91, specificity of 0.38, PPV of 0.18, and NPV of 0.97. INTEM CT >205 seconds had a sensitivity of 0.97, specificity of 0.11, PPV of 0.57, and NPV of 0.75 for aPTT ≥38.5 seconds. These values were similar for the subset of patients with normal FIBTEM A5. CONCLUSIONS: EXTEM CT >80 seconds and HEPTEM CT >280 seconds have high sensitivities and NPVs for INR >2.0, which would effectively "rule out" INR >2.0 as a cause for excessive bleeding. However, the low specificities and PPVs indicate they would be less effective in ruling it in. INTEM CT >205 seconds had low PPV and NPV in identifying aPTT >38.5 seconds.

The Use of Extracorporeal Circulation to Facilitate the Resection of a Large Retroperitoneal Sarcoma With Major Vessel Involvement: A Single-Center Review of 20 Cases.

OBJECTIVE: To describe the introduction of extracorporeal corporeal oxygenation (ECMO) to facilitate the surgical resection of large retroperitoneal sarcomas involving major vessels and to report preliminary outcomes. DESIGN: A case series. SETTING: At a tertiary university hospital and state sarcoma center. PARTICIPANTS: Patients undergoing retroperitoneal sarcoma resection requiring inferior vena cava (IVC) reconstruction between June 2018 and March 2022. INTERVENTION: ECMO for retroperitoneal tumor resection requiring IVC reconstruction. MEASUREMENTS AND MAIN RESULTS: A total of 20 patients underwent ECMO-assisted retroperitoneal sarcoma resection and IVC reconstruction. The median age was 60.5 years (IQR 48-69); 15 women and 5 men. The median procedure and ECMO durations were 10.8 hours (IQR 8.5-12.4 hours) and 2.2 hours (IQR 62-218 minutes), respectively. The median intensive care unit and hospital lengths of stay were 4 days (IQR 3-5 days) and 21 days (IQR 14-31 days), respectively. All 20 patients received packed cell transfusions (median 8 per patient [IQR 4-14]); 11 patients required fresh frozen plasma, 6 required platelets, and 11 required fibrinogen supplementation. One patient required recombinant activated factor VII. Sixteen patients experienced acute kidney injury, with 12 patients progressing to chronic kidney disease. Three patients were required to return to the operating room within 7 days, with no returns within the first 24 hours. There was no in-hospital or 30-day mortality. Survival at 3 years was 84%. CONCLUSIONS: ECMO for resecting large retroperitoneal tumor resection was introduced successfully and facilitated satisfactory outcomes for many patients who might otherwise have been considered too high risk.

Optic Nerve Sheath Diameter Increase on Ascent to High Altitude: Correlation With Acute Mountain Sickness.

OBJECTIVES: Elevated optic nerve sheath diameter on sonography is known to correlate with increased intracranial pressure and is observed in acute mountain sickness. This study aimed to determine whether optic nerve sheath diameter changes on ascent to high altitude are associated with acute mountain sickness incidence. METHODS: Eighty-six healthy adults enrolled at 1240 m (4100 ft), drove to 3545 m (11,700 ft) and then hiked to and slept at 3810 m (12,500 ft). Lake Louise Questionnaire scores and optic nerve sheath diameter measurements were taken before, the evening of, and the morning after ascent. RESULTS: The incidence of acute mountain sickness was 55.8%, with a mean Lake Louise Questionnaire score ± SD of 3.81 ± 2.5. The mean maximum optic nerve sheath diameter increased on ascent from 5.58 ± 0.79 to 6.13 ± 0.73 mm, a difference of 0.91 ± 0.55 mm (P = .09). Optic nerve sheath diameter increased at high altitude regardless of acute mountain sickness diagnosis; however, compared to baseline values, we observed a significant increase in diameter only in those with a diagnosis of acute mountain sickness (0.57 ± 0.77 versus 0.21 ± 0.76 mm; P = .04). This change from baseline, or Δ optic nerve sheath diameter, was associated with twice the odds of developing acute mountain sickness (95% confidence interval, 1.08-3.93). CONCLUSIONS: The mean optic nerve sheath diameter increased on ascent to high altitude compared to baseline values, but not to a statistically significant degree. The magnitude of the observed Δ optic nerve sheath diameter was positively associated with acute mountain sickness diagnosis. No such significant association was found between acute mountain sickness and diameter elevation above standard cutoff values, limiting the utility of sonography as a diagnostic tool.

An audit of the diagnostic accuracy of the ROTEM®sigma for the identification of hypofibrinogenaemia in cardiac surgical patients.

The ROTEM®delta (TEM Innovations GmbH, Munich, Germany) has been used extensively worldwide for the assessment of coagulation in cardiac surgical patients. Recently, a new cartridge-based ROTEM device (ROTEM®sigma, TEM Innovations GmbH, Munich, Germany) has become available. In this paper we report an audit of the diagnostic accuracy of the ROTEM sigma for the identification of hypofibrinogenaemia in cardiac surgical patients. We hypothesised that the diagnostic accuracy of the ROTEMsigma for the identification of hypofibrinogenaemia would be in a similar range to that previously reported for the ROTEMdelta. Simultaneous blood samples for Clauss laboratory fibrinogen and ROTEMsigma FIBTEM measurements were obtained immediately after heparin reversal post-cardiopulmonary bypass in 200 adult cardiac surgical patients. The sensitivity, specificity, and positive and negative predictive values for FIBTEM A5 and A10 for the identification of hypofibrinogenaemia (Clauss fibrinogen <1.5 g/l) were calculated. The prevalence of hypofibrinogenaemia across the 200 patients was 8%. The mean sensitivity and specificity of FIBTEM A10 ≤8 mm for the identification of hypofibrinogenaemia were 0.75 and 0.90 respectively, which are in a similar range to that reported in several previous studies using the ROTEMdelta. For FIBTEM A5 ≤6 mm the values were 0.63 and 0.98 respectively. The predictive values were also in a similar range to those previously reported for the ROTEMdelta, with low false negative rates (2% for A10 ≤8 mm; 3% for A5 ≤6 mm). These findings support the use of the ROTEMsigma as an alternative to the ROTEMdelta for the identification of hypofibrinogenaemia post-cardiopulmonary bypass in cardiac surgical patients. However, further studies are required in other settings.

Investigation of a His-rich arabinogalactan-protein for micronutrient biofortification of cereal grain.

The micronutrient content of most cereal grains is low and responsible for malnutrition deficiencies in millions of people who rely on grains as their primary food source. Any strategy that can increase the micronutrient content of grain will have significant benefits to world health. We identified a gene from barley encoding a cell wall protein with multiple histidine (His)-rich motifs interspersed with short arabinogalactan-protein (AGP) domains and have called it Hordeum vulgare His-rich AGP (HvHRA1). Sequence analysis shows that His-rich AGPs are rare in plants and that the number of His-rich and AGP domains differ between cereals and dicots. The barley and wheat encoded proteins have more than 13 His-rich domains, whereas the putative rice orthologue has only 5 His-rich regions. His-rich motifs are well-established metal-binding motifs; therefore, we developed transgenic (Tx) rice plants that constitutively overexpress barley HvHRA1. There was no significant effect on plant growth or grain yield in Tx plants. Purification of AGPs from wild-type and Tx plants showed that only Tx plants contained detectable levels of a His-rich AGP. Calcein assay shows that the AGP fraction from Tx plants had increased binding affinity for Cu(2+) . Micronutrient analysis of brown and white rice showed that the grain nutrient yield for Fe, Zn and Cu was higher in two Tx lines compared to their respective nulls, although the differences were not statistically significant. This approach highlights the potential of the plant apoplast (cell wall) for storage of key nutrients through overexpression of genes for metal-binding proteins.

Cosmetic outcomes following wide local excision of impalpable breast cancer: is radioguided occult lesion localization using iodine-125 seeds better than hookwire localization?

BACKGROUND: Hookwire localization (HWL) is the gold standard for localizing impalpable tumours for breast conserving surgery. An alternative technique, radioguided occult lesion localization using iodine-125 seeds (ROLLIS), has been associated with lower re-excision rates. This paper investigates if cosmetic outcomes differ in women undergoing breast conserving surgery with HWL or ROLLIS. METHODS: Women who had ROLLIS or HWL guided excision for impalpable breast cancer within a multicentre randomized controlled trial (RCT) (ANZCTR 12613000655741) were recruited. Exclusions were level 2 oncoplasty and mastectomy. Cosmetic outcome was calculated using BCCT.core, the Hopwood Body Image Scale and estimated percentage breast volume excised. Chi-squared analysis was used to determine the difference between the intervention groups. RESULTS: Analysis was performed for 123 participants (66 ROLLIS and 57 HWL). The cosmetic outcome determined by BCCT.core for all participants was good with no significant difference between the ROLLIS and HWL groups. When reviewing the number of patients who experienced either a good or excellent result, there was a significantly higher number of patients in the ROLLIS group (n = 53, 82%) compared to the HWL group (n = 42, 74%, P = 0.02. There were no differences in Hopwood Body Image Scale or estimated percentage breast volume excised between groups. There was a reduction in the frequency of re-excision in the ROLLIS group (n = 3, 4.5%) versus HWL group (n = 8, 14%); however, this was not significant (P = 0.06). CONCLUSION: Pre-operative localization of impalpable breast lesions using either ROLLIS or HWL resulted in a good cosmetic outcome with no significant difference between localization techniques.

Increased inspired oxygen concentration does not adversely affect oxidative stress and the resolution of inflammation during reperfusion in patients undergoing knee replacement surgery.

The level of inspired oxygen during surgery may modify free radical release, and reperfusion injury. This controlled trial examined the effect of inspired oxygen on F2-isoprostanes (F2-IsoPs), isofurans (IsoFs), and specialized mediators of inflammation resolution (SPM) during knee replacement surgery. Patients received either 30% O2 (control n = 21), 50% O2 (n = 20), or 80% O2 (n = 19) O2, in a parallel design. Hemoglobin (Hb) was measured throughout the surgery and F2-IsoPs, IsoFs and SPM were analyzed by mass spectrometry. The effect of O2 on F2-IsoPs and IsoFs was examined during tourniquet inflation and after tourniquet release. SPM were measured at baseline and the end of surgery. There was a significant interaction between O2 and Hb concentrations with plasma IsoFs during tourniquet inflation. An increase in plasma IsoFs over time was attenuated in the 80% O2 group (p=.012) compared with the 30% O2 group after adjusting for Hb concentration. After tourniquet release, plasma F2-IsoPs were significantly lower in the 50% and 80% O2 groups (p=.009 and p=.001, respectively) compared with the 30% O2 group after adjustment for Hb concentration. The SPM RvD2 and RvE2 were increased with 50% and 80% O2 (RvD2, p=.014 and p=.002, respectively; RvE2, p=.032 with 50% O2) compared with the 30% O2 group, in analyses that corrected for Hb concentration. We have shown for the first time that higher O2 levels may be beneficial in reducing oxidative stress and increasing resolution of inflammation during surgery that involves reperfusion after application of a tourniquet.

Anaphylaxis to intravenous paracetamol containing povidone. A case report and narrative review of excipient allergy related to anaesthesia.

Investigation of intraoperative anaphylaxis includes the exclusion of potential trigger agents the individual was exposed to within a plausible interval preceding the reaction. Occasionally, none of these agents will test positive. In this situation it is important to consider that excipients may be responsible for anaphylaxis, that the dilutions prepared to test the medication may not contain an appropriate concentration of the excipient to induce a positive skin reaction, or if an alternative formulation of the medication is tested, it may not contain the culprit excipient. This case describes a patient, who previously experienced an anaphylactic reaction to Betadine® (Sanofi-Aventis Australia Pty Ltd, North Ryde BC, NSW) experiencing anaphylaxis in the recovery period after general anaesthesia where Betadine was avoided. The recently administered therapeutics were excluded by skin testing, however further investigation determined that a povidone-containing formulation of paracetamol had been administered. Skin testing with povidone-containing paracetamol resulted in a positive reaction in the patient, but not in a volunteer control. Pharmaceutical excipients are added to medications to increase absorption, shelf-life and efficacy. Different brands of the same drug may contain different excipients. When testing for anaphylaxis with such compounds one must be sure the dilution is appropriate for both the parent compound and the excipient to ensure the accuracy of skin-prick and intradermal testing. This case demonstrates the potential for excipients to cause severe allergy and the importance of detailed history pertaining to previous allergic episodes as even the most unlikely of medications can potentially result in anaphylaxis due to excipients.

Monitoring electrical skin conductance: a tool for the assessment of postoperative pain in children?

BACKGROUND: Monitoring changes in electrical skin conductance has been described as a potentially useful tool for the detection of acute pain in adults. The aim of this study was to test the method in pediatric patients. METHODS: A total of 180 postoperative pediatric patients aged 1-16 yr were included in this prospective, blinded observational study. After arrival in the recovery unit, pain was assessed by standard clinical pain assessment tools (1-3 yr: Face Legs Activity Cry Consolability Scale, 4-7 yr: Revised Faces Scale, 8-16 yr: Visual Analogue Scale) at various time points during their stay in the recovery room. The number of fluctuations in skin conductance per second (NFSC) was recorded simultaneously. RESULTS: Data from 165 children were used for statistical analysis, and 15 patients were excluded. The area under the Receiver Operating Characteristic curve for predicting moderate to severe pain from NFSC was 0.82 (95% confidence interval 0.79-0.85). Over all age groups, an NFSC cutoff value of 0.13 was found to distinguish between no or mild versus moderate or severe pain with a sensitivity of 90% and a specificity of 64% (positive predictive value 35%, negative predictive value 97%). CONCLUSIONS: NFSC accurately predicted the absence of moderate to severe pain in postoperative pediatric patients. The measurement of NFSC may therefore provide an additional tool for pain assessment in this group of patients. However, more research is needed to prospectively investigate the observations made in this study and to determine the clinical applicability of the method.

The effects of neostigmine and glycopyrrolate on skin conductance as a measure of pain.

BACKGROUND AND OBJECTIVE: The number of fluctuations in skin conductance per second has been shown to correlate with postoperative pain. In this context, the effects of cholinesterase inhibitors and anticholinergic drugs used for the reversal of muscle relaxants were investigated. METHODS: Muscle relaxant effects were reversed in 30 patients with neostigmine and glycopyrrolate. No reversal agents were given to 30 controls. Patients' level of pain was quantified using a numeric rating scale (0-10) at several time points in the recovery room. The number of fluctuations in skin conductance per second was measured simultaneously. RESULTS: The number of fluctuations in skin conductance per second was significantly higher in patients with no and severe pain in the control compared with the reversal group (no pain 0.19 vs. 0.12; severe pain 0.40 vs. 0.19). The number of fluctuations in skin conductance per second was less sensitive to identify time points with moderate/severe pain in the reversal group. CONCLUSION: Skin conductance-based assessment of pain is affected by reversal agents.