Development and validation of an LC-MSMS method to quantify creatinine from dried blood spots.

Introduction: Screening for chronic kidney disease relies on accurate and precise creatinine measurements. Traditionally, creatinine is measured in serum or plasma using high-throughput chemistry analyzers. However, dried blood spots (DBS) can also be utilized to improve testing access. Methods: Samples were obtained from a 6 mm DBS punch, which was reconstituted in water before undergoing an acetonitrile crash. The resulting supernatant was diluted using an 80:20 acetonitrile: water before injection. Creatinine was identified using an isocratic gradient, and detected using an API 4000 triple quadrupole mass analyzer. Quantification relied on matrix-matched calibrators, with values harmonized to the Roche Cobas enzymatic assay. Validation studies assessing method performance included precision, linearity, accuracy, method comparison, stability, interference, and matrix effects. Results: The LC-MSMS assay was linear from 0.3 to 20 mg/dL (y = 1.02x-0.11; R2 = 0.996). Precision ranged from 5.2 to 8.1 % using matrix-matched controls (n = 4) that spanned the analytical measurement range. LC-MSMS results corresponded to the enzymatic assay (Roche) with a fitted line equation of y = 0.956x-0.07 (R2 = 0.995; n = 173). The Siemens and Roche enzymatic assays demonstrated higher accuracy in correlating to the DBS creatinine concentration (n = 40 paired venous/DBS collections) compared to the Beckman Jaffe assay (-2.5 % and -0.8 % versus -6.3 % and -4.1 %, respectively) or the iSTAT (-28.4 % and -27.1 %, respectively). Accuracy was unaffected by hematocrit, blood spot volume, excess IgG or IgA, or hypertriglyceridemia. No matrix effects were observed, and both extraction and processing efficiency were robust.Ambient stability extended to at least 10 days, and exposure to extreme temperature did not affect the creatinine results. Conclusion: We successfully developed an accurate and precise LC-MSMS method for quantifying creatinine in DBS.

Matrix-matched calibrators are necessary for robust and high-quality dried blood spots lead screening assays by inductively coupled plasma-mass spectrometry.

Background and aims: Reliable lead screening methods are necessary to support early identification of lead exposure in children. Sample collection using dried blood spots (DBS) offers advantages compared to traditional venipuncture and capillary collection. Here, we describe and compare three lead DBS inductively coupled plasma-mass spectrometry (ICP-MS) methods for lead screening. Materials and methods: Lead was extracted from Whatman 903 protein saver cards punches and analyzed by ICP-MS across three independent clinical laboratories. Each laboratory evaluated the performance of aqueous and matrix-matched DBS calibrators using external quality control samples (WI State of Laboratory of Hygiene Program). Leftover patient samples (n = 39) were used for an interlaboratory comparison of lead DBS. Lead DBS results were compared to whole blood methods. Results: The DBS ICP-MS methods using matrix-matched DBS calibrators had superior performance to the aqueous calibrations. There was a strong correlation between lead measured in DBS (matrix-matched) and whole blood for the three methods evaluated. Conclusion: Lead can be measured accurately by ICP-MS in DBS samples when matrix-matched calibrators are used. External quality control programs are valuable to assess the performance of DBS methods. DBS lead ICP-MS methods are a robust analytical option for lead screening even though the limitations of DBS are well recognized.

Applying Magnetic Curvature to MMS Data to Identify Thin Current Sheets Relative to Tail Reconnection.

Thin current sheets (TCSs) have been postulated to be a necessary precondition for reconnection onset. Magnetic reconnection X-lines in the magnetotail have been observed to be more common duskward of midnight. We take advantage of the MMS tetrahedral formation during the 2017-2020 MMS tail seasons to calculate the thickness of the cross-tail neutral sheet relative to ion gyroradius. While a similar technique was applied to Cluster data, current sheet thickness over a broader range of radial distances has not been robustly explored before this study. We compare our analysis to recent theories regarding mechanisms of tail current sheet thinning and to recent simulations. We find MMS spent more than twice as long in ion-scale TCSs in the pre-midnight sector than post-midnight, despite nearly even plasma sheet dwell time. The dawn-dusk asymmetry in the distribution of Ion Diffusion Regions, as previously reported in relation to regions of TCSs, is also analyzed.

Airo® navigation versus freehand fluoroscopy technique: A comparative study of accuracy and radiological exposure for thoracolumbar screws placement.

PURPOSE: The aim was to compare the accuracy of freehand fluoroscopy and CT based navigation on thoracolumbar screws placement and their respective effects on radiological exposure to the patient. No previous study directly compared the Airo® navigation system to freehand technique. METHODS: In this monocentric retrospective study, 156 consecutive patients who underwent thoracolumbar spine surgery were included. Epidemiological data and surgical indications were noted. Heary classification was used for thoracic screws and Gertzbein-Robbins classification for lumbar screws. Radiological exposure was collected for each surgery. RESULTS: A total of 918 screws were implanted. We analyzed 725 lumbar screws (Airo® 287; freehand fluoroscopy 438) and 193 thoracic screws (Airo® 49; freehand fluoroscopy 144). Overall, lumbar screws accuracy (Gertzbein-Robbins grade A and B) was good in both groups (freehand fluoroscopy 91.3%; Airo® 97.6%; P<0.05). We found significantly less Grade B and C in the Airo® group. Thoracic accuracy was also good in both groups (Heary 1 and 2; freehand fluoroscopy 77.8%; Airo® 93.9%), without reaching statistical significance. Radiological exposure was significantly higher in the Airo® group with a mean effective dose of 9.69 mSv versus 0.71mSv for freehand fluoroscopy. CONCLUSION: Our study confirmed that the use of Airo® navigation yielded good accuracy. It however exposed the patient to higher radiological exposure compared with freehand fluoroscopy technique. LEVEL OF EVIDENCE: Level 3.

[Treatment of 52 patients with a self-adhesive siliconised superabsorbent dressing: a multicentre observational study]. / Lechenie ran u 52 patsientov s primeneniem samokleyashcheisya silikonizirovannoi superabsorbiruyushchei povyazki: mnogotsentrovoe nablyudatel'noe issledovanie.

OBJECTIVE: To provide 'in use' clinical data to support exudate management in patients with moderately to highly exuding wounds with bordered superabsorbent wound dressing with a silicone adhesive interface Zetuvit Plus Silicone Border (Paul Hartmann Ltd., Germany). MATERIALS AND METHODS: This study was an open-labelled non-comparative study. Patients included in the study were selected by the clinical investigator(s) according to whether the patient required a dressing for the management of moderately to highly exuding wounds such as pressure ulcers, diabetic foot ulcers, venous leg ulcer and arterial ulcers The patients were treated with A superabsorbent sterile wound dressing with bordered superabsorbent wound dressing with a silicone adhesive interface Zetuvit Plus Silicone Border (Paul Hartmann Ltd., Germany). RESULTS: The Zetuvit Plus Silicone Border dressing had met the clinical objectives relating to exudate management, affirmed by the health professionals with a yes response in 94% of cases. Additionally, the health professionals rated the handling of exudate as excellent/good (78%) and most (80%) reported that they would use the superabsorbent wound dressing with a silicone adhesive interface again. Allied to this was the fact that the dressing improved the wound edge and periwound skin conditions (29% and 36% of patients, respectively). The dressing retained its position in 72% of patients. For wear time, the largest proportion of dressing changes, both pre-study and during the evaluation period, was every third day (45% and 44%, respectively). But there was a shift to extended wear time with use of the superabsorbent wound dressing with a silicone adhesive interface with 72% of patients' dressing changes being every third day or longer. CONCLUSION: The superabsorbent silicone border dressing was successful in managing wound exudate in moderately to highly exuding wounds and consequently this had a beneficial impact on the wound edge and periwound skin. Overall, there was a positive effect on wound bed preparation and in turn the healing response was progressive.

Does gabapentin provide benefit for patients with knee OA? A benefit-harm and cost-effectiveness analysis.

OBJECTIVE: Gabapentin can treat neuropathic pain syndromes and has increasingly been prescribed to treat nociplastic pain. Some patients with knee osteoarthritis (OA) suffer from both nociceptive and nociplastic pain. We examined the cost-effectiveness of adding gabapentin to knee OA care. METHOD: We used the Osteoarthritis Policy Model, a validated Monte Carlo simulation of knee OA, to examine the value of gabapentin in treating knee OA by comparing three strategies: 1) usual care, gabapentin sparing (UC-GS); 2) targeted gabapentin (TG), which provides gabapentin plus usual care for those who screen positive for nociplastic pain on the modified PainDETECT questionnaire (mPD-Q) and usual care only for those who screen negative; and 3) universal gabapentin plus usual care (UG). Outcomes included cumulative quality-adjusted life years (QALYs), lifetime direct medical costs, and incremental cost-effectiveness ratios (ICERs), discounted at 3% annually. We derived model inputs from published literature and national databases and varied key input parameters in sensitivity analyses. RESULTS: UC-GS dominated both gabapentin-containing strategies, as it led to lower costs and more QALYs. TG resulted in a cost increase of $689 and a cumulative QALY reduction of 0.012 QALYs. UG resulted in a further $1,868 cost increase and 0.036 QALY decrease. The results were robust to plausible changes in input parameters. The lowest TG strategy ICER of $53,000/QALY was reported when mPD-Q specificity was increased to 100% and AE rate was reduced to 0%. CONCLUSION: Incorporating gabapentin into care for patients with knee OA does not appear to offer good value.

A comparison of self-reported risk and protective factors and the death implicit association test in the prediction of future suicide attempts in adolescent emergency department patients.

BACKGROUND: Concerns have been raised about the utility of self-report assessments in predicting future suicide attempts. Clinicians in pediatric emergency departments (EDs) often are required to assess suicidal risk. The Death Implicit Association Test (IAT) is an alternative to self-report assessment of suicidal risk that may have utility in ED settings. METHODS: A total of 1679 adolescents recruited from 13 pediatric emergency rooms in the Pediatric Emergency Care Applied Research Network were assessed using a self-report survey of risk and protective factors for a suicide attempt, and the IAT, and then followed up 3 months later to determine if an attempt had occurred. The accuracy of prediction was compared between self-reports and the IAT using the area under the curve (AUC) with respect to receiver operator characteristics. RESULTS: A few self-report variables, namely, current and past suicide ideation, past suicidal behavior, total negative life events, and school or social connectedness, predicted an attempt at 3 months with an AUC of 0.87 [95% confidence interval (CI), 0.84-0.90] in the entire sample, and AUC = 0.91, (95% CI 0.85-0.95) for those who presented without reported suicidal ideation. The IAT did not add significantly to the predictive power of selected self-report variables. The IAT alone was modestly predictive of 3-month attempts in the overall sample ((AUC = 0.59, 95% CI 0.52-0.65) and was a better predictor in patients who were non-suicidal at baseline (AUC = 0.67, 95% CI 0.55-0.79). CONCLUSIONS: In pediatric EDs, a small set of self-reported items predicted suicide attempts within 3 months more accurately than did the IAT.

Delayed axial flaps for coverage of a fourth degree scalp burn.

Although free tissue transfers may be required to cover wounds of the head and neck with bone involvement and exposure, options lower on the reconstructive ladder should still be considered during the planning process. We present a case of an elderly gentleman with a history of cardiovascular comorbidity and neck radiotherapy, who sustained a deep flame burn injury to his scalp. Two delayed axial flaps, based on the superficial temporal and supraorbital arteries respectively, were used to obtain durable coverage of this complex wound.

The impact of coronavirus disease 2019 on the head and neck cancer pathway in the West of Scotland.

OBJECTIVE: The coronavirus disease 2019 pandemic has greatly disrupted head and neck cancer services in the West of Scotland. This study aimed to assess the impact of the first wave of the pandemic on cancer waiting times. METHODS: A retrospective review of multidisciplinary team records was undertaken between March and May in 2019 and the same months in 2020. Time-to-diagnosis and time-to-treatment for new cancers treated with curative intent were compared between the study periods, and subclassified by referral pathway. RESULTS: A total of 236 new cancer patients were included. During the pandemic, pathways benefitted from reduced diagnostic and treatment times resulting from the restructuring of service provisions. A 75 per cent reduction in secondary care referrals and a 33 per cent increase in urgent suspicion of cancer referrals were observed in 2020. CONCLUSION: Head and neck cancer pathway times did not suffer because of the coronavirus pandemic. Innovations introduced to mitigate issues brought about by coronavirus benefitted patients, led to a more streamlined service, and improved diagnostic and treatment target compliance.

A systematic review: impact of in-office biopsy on safety and waiting times in head and neck cancer.

OBJECTIVE: This study aimed to assess the current literature on the safety and impact of in-office biopsy on cancer waiting times as well as review evidence regarding cost-efficacy and patient satisfaction. METHOD: A search of Cinahl, Cochrane Library, Embase, Medline, Prospero, PubMed and Web of Science was conducted for papers relevant to this study. Included articles were quality assessed and critically appraised. RESULTS: Of 19 741 identified studies, 22 articles were included. Lower costs were consistently reported for in-office biopsy compared with operating room biopsy. Four complications requiring intervention were documented. In-office biopsy is highly tolerated, with a procedure abandonment rate of less than 1 per cent. When compared with operating room biopsy, it is associated with significantly reduced time-to-diagnosis and time-to-treatment initiation. It is linked to improved overall three-year survival. CONCLUSION: In-office biopsy is a safe procedure that may help certain patients avoid general anaesthetic. It was shown to significantly reduce time-to-diagnosis and time-to-treatment initiation when compared with operating room biopsy. This may have important implications for oncological outcomes. In-office biopsy requires fewer resources and is likely to be cost-saving five-years following introduction. With high rates of sensitivity and specificity, in-office biopsy should be considered as the first-line procedure to achieve tissue diagnosis.

Choosing wisely in burn care.

BACKGROUND: The Choosing Wisely Campaign was launched in 2012 and has been applied to a broad spectrum of disciplines in almost thirty countries, with the objective of reducing unnecessary or potentially harmful investigations and procedures, thus limiting costs and improving outcomes. In Canada, patients with burn injuries are usually initially assessed by primary care and emergency providers, while plastic or general surgeons provide ongoing management. We sought to develop a series of Choosing Wisely statements for burn care to guide these practitioners and inform suitable, cost-effective investigations and treatment choices. METHODS: The Choosing Wisely Canada list for Burns was developed by members of the Canadian Special Interest Group of the American Burn Association. Eleven recommendations were generated from an initial list of 29 statements using a modified Delphi process and SurveyMonkey™. RESULTS: Recommendations included statements on avoidance of prophylactic antibiotics, restriction of blood products, use of adjunctive analgesic medications, monitoring and titration of opioid analgesics, and minimizing 'routine' bloodwork, microbiology or radiological investigations. CONCLUSIONS: The Choosing Wisely recommendations aim to encourage greater discussion between those involved in burn care, other health care professionals, and their patients, with a view to reduce the cost and adverse effects associated with unnecessary therapeutic and diagnostic procedures, while still maintaining high standards of evidence-based burn care.

A case of intramuscular lumbar myxoma: Uncertainty in the preoperative diagnosis of a spinal soft tissue tumour.

We report an uncommon case of a 76-year-old woman who presented with lower back pain, an intermittent L5 radiculopathy and a right palpable paraspinal mass. Imaging studies revealed a 7-cm lumbar paraspinal pseudo-cystic soft tissue tumour developed in the paravertebral musculature, without a clear radiological diagnosis. Gross total surgical resection was performed, resulting in complete resolution of pain. Histopathological studies revealed an intramuscular (IM) myxoma. With a low positive predictive value of radiological work-up and a poor yield of percutaneous biopsies, surgery remains the mainstay treatment for these rare soft tissue tumours of the lumbar spine. Intramuscular myxomas show excellent postoperative results.

Learning from mistakes when reporting urgent and emergency vascular studies.

The majority of out-of-hours cases relate to neurological, chest, and gastrointestinal pathologies with acute vascular cases being encountered less commonly. Trainees and exposure of non-vascular/interventional radiology (IR) consultants to angiographic imaging is often limited in working hours and this may lead to reporting on-call cases outside of normal daytime practice. In a recent local review, a number on-call vascular studies were found to contain a number of vascular-related discrepancies. Vascular reporting is a complex subspecialty, which comprises many clear diagnoses (large vessel occlusions, large vessel aneurysms, or dissections); however, also several subtle and complex abnormalities. These more subtle abnormalities, at times, require dedicated vascular specialist review to ensure subtle findings are communicated appropriately to the clinical team. The recent increased complexity of endovascular treatments and their complications has also provided further challenge for the non-specialist reporter. Similarly, improved imaging techniques have allowed for non-obvious but significant findings that may require urgent management, such as small aneurysms and dissection flaps. We will review a range of key vascular findings that demonstrate learning opportunities, particularly within the acute and on-call settings. These will include gastrointestinal haemorrhage, subtle aortic pathologies, head and neck vascular emergencies, small to mid-sized vessel injuries and imaging of post-procedural complications. Educational hints and tips will be provided to enable learning from mistakes encountered by trainees and non-vascular specialist radiologists in the on-call or urgent reporting settings, and these will be reviewed with reference to the literature.

Investigating the Role of Amazonian Mesoscale Wind Patterns and Strength on the Spatial Distribution of Martian Bedrock Exposures.

The Martian highlands contain Noachian-aged areally-extensive (>225 km2) bedrock exposures that have been mapped using thermal and visible imaging datasets. Given their age, crater density and impact gardening should have led to the formation of decameter scale layers of regolith that would overlie and bury these outcrops if composed of competent materials like basaltic lavas. However, many of these regions lack thick regolith layers and show clear exposures of bedrock materials with elevated thermal inertia values compared to the global average. Hypothesized reasons for the lack of regolith include: (a) relatively weaker material properties than lavas, where friable materials are comminuted and deflated during wind erosion, (b) long-term protection from regolith development through burial and later exhumation through one or more surface processes, and (c) spatially concentrated aeolian erosion and wind energetics on well-lithified basaltic substrates. To test the third hypothesis, we used the Mars Regional Atmospheric Modeling System to calculate wind erosive strength at 10 regions throughout the Martian highlands and compared it to their thermophysical properties by using thermal infrared data derived from the Thermal Emission Spectrometer to understand the effect that Amazonian mesoscale wind patterns may have on the exposure of bedrock. We also investigated the effect of planet obliquity, Ls of perihelion, and atmospheric mean pressure on wind erosion potential. We found no evidence for increased aeolian activity over bedrock-containing regions relative to surrounding terrains, including at the mafic floor unit at Jezero crater (Máaz formation), supporting the first or second hypotheses for these regions.

Optimal timing and technique for endoscopic management of dysphagia in pediatric aerodigestive patients.

INTRODUCTION: The best strategy to manage an interarytenoid defect [Type 1 laryngeal cleft (LC-1) or deep interarytenoid groove (DIG)] in pediatric aerodigestive patients with dysphagia remains uncertain. This study compared benefit of interarytenoid augmentation (IAA) to suture repair or clinical observation alone in pediatric patients. METHODS: A 3-year retrospective, single-center analysis of children with dysphagia undergoing endoscopic airway evaluation was performed. Physician preference guided treatment plan: suture repair with CO2 laser, IAA (carboxy methylcellulose or calcium hydroxyapatite), or observation. Primary outcome was improved post-operative diet. Significance was assumed at p < 0.05. RESULTS: 449 patients underwent diagnostic endoscopy. Mean age (±SD) at procedure was 21 ± 13 months, with nearly one fourth (28 %) of children ≤ 12 months. Eighty (18 %) had either an LC-1 (n = 55) or DIG (n = 25). Of these, 35 (42 %) underwent suture repair, 22 (28 %) IAA, and 23 (30 %) observation only. Aspiration improved overall in the interventional groups compared to observational controls (58 % vs. 9 %, p < 0.05), with no change in benefit observed by age of intervention. IAA was as effective as suture repair (59 % vs 55 %, p = 0.46). In patients with only a DIG, IAA intervention alone significantly improved swallow function (66.6 % vs. 0 %, p < 0.05). CONCLUSION: In pediatric aerodigestive patients with dysphagia, 18 % of children have an addressable lesion. IAA or suture repair similarly improves dietary advancement. IAA improves swallow function in patients with DIG. These findings support a novel protocol to intervene in dysphagia patients with LC-1 or DIG via IAA at the initial operative evaluation.

Flap coverage for necrotising soft tissue infections: A systematic review.

BACKGROUND: Necrotising soft tissue infections (NSTI) are destructive and often life-threatening infections of the skin and soft tissue, necessitating prompt recognition and aggressive medical and surgical treatment. After debridement, the aim of surgical closure and reconstruction is to minimize disability and optimize appearance. Although skin grafting may fulfil this role, techniques higher on the reconstructive ladder, including local, regional and free flaps, are sometimes undertaken. This systematic review sought to determine the circumstances when this is true, which flaps were most commonly employed, and for which anatomical areas. METHODS: A systematic review of the literature was conducted utilising electronic databases (Medline, Embase, Cochrane Library). Full text studies of flaps used for the management of NSTI's (including Necrotising Fasciitis and Fournier Gangrene) were included. The web-based program 'Covidence' facilitated storage of references and data management. Data obtained in the search included reference details (journal, date and title), the study design, the purpose of the study, the study findings, number of patients with NSTI included, the anatomical areas of NSTI involved, the types of flaps used, and the complication rate. RESULTS: After screening 4555 references, 501 full text manuscripts were assessed for eligibility after duplicates and irrelevant studies were excluded. 230 full text manuscripts discussed the use of 888 flap closures in the context of NSTI in 733 patients; the majority of these were case series published in the last 20 years in a large variety of journals. Reconstruction of the perineum following Fournier's gangrene accounted for the majority of the reported flaps (58.6%). Free flaps were used infrequently (8%), whereas loco-regional muscle flaps (18%) and loco-regional fasciocutaneous flaps (71%) were employed more often. The reported rate of partial or complete flap loss was 3.3%. CONCLUSION: Complex skin and soft tissue defects from NSTIs, not amenable to skin grafting, can be more effectively and durably covered using a spectrum of flaps. This systematic review highlights the important contribution that the plastic surgeon makes as an integral member of multidisciplinary teams managing these patients.