Anesthetic management of parturients with achondroplasia: a case series.

Background: Achondroplasia is the most common form of dwarfism, and cesarean delivery is often required in parturients with achondroplasia due to cephalopelvic disproportion. Given the challenges for both regional and general anesthetic techniques, there is no consensus on the optimal anesthetic management for cesarean delivery in these patients. Method: A search of our electronic medical records for all female patients who had a diagnosis of achondroplasia and had a delivery in our health system from January 1, 2001 through June 16, 2023 was performed. Institutional review board exemption was obtained. Results: We identified seven achondroplastic patients with 12 cesarean deliveries and described their anesthetic management during labor and delivery. Conclusion: Despite the historical preference of general anesthesia in achondroplastic patients due to concerns of unpredictable spinal anatomy and unreliable local anesthetic spread, neuraxial anesthesia was successfully utilized in achondroplastic parturients and is a viable option in carefully selected patients. Reduction of intrathecal local anesthetic dose that minimizes the risk of high spinal and emergent intubation, as well as a titratable neuraxial technique, can be effective in this patient population.

The complementarity of phosphatidylethanol in whole blood and ethyl glucuronide in hair as biomarkers for the monitoring of alcohol use.

Monitoring long-term alcohol use and/or abstinence is essential in clinical and medico-legal cases. Analysis of ethyl glucuronide (EtG) in hair provides information on alcohol consumption over several months. However, there is a lag time between ethanol consumption, incorporation of EtG in the hair bulb and hair growing out of the scalp. Phosphatidylethanol (PEth) 16:0/18:1 analysis in whole blood has a detection window of 2-4 weeks, allowing for the detection of recent alcohol consumption. In this study, 2340 paired samples (of hair and venous whole blood from 1170 individuals) were analysed for EtG in hair (hEtG) and PEth 16:0/18:1 in venous whole blood. PEth 16:0/18:1 and hEtG results were subdivided into three categories according to the consensus of SoHT (hEtG) and PEth-NET (PEth): abstinence/low, moderate or excessive alcohol consumption. For hEtG analysis, 446 individuals presented abstinence/low alcohol consumption, of which 2% were classified as excessive alcohol users through PEth 16:0/18:1 analysis. This suggests excessive alcohol consumption in the weeks before sample collection. Out of 483 individuals classified as heavy alcohol users based on hEtG analysis, 14% showed abstinence/low alcohol consumption for PEth 16:0/18:1 analysis, implying that these subjects stopped drinking 2-4 weeks before sample collection. Our results show that the analysis of the two different biomarkers can lead to a more accurate categorisation of individuals. Therefore, we emphasize that for the retrospective investigation of alcohol use, it is necessary to include two alcohol use biomarkers with different detection windows.

Hair as an alternative matrix to assess exposure of premature neonates to phthalate and alternative plasticizers in the neonatal intensive care unit.

Due to adverse health effects, di-(2-ethylhexyl) phthalate (DEHP), a plasticizer used to soften plastic medical devices (PMDs), was restricted, and gradually replaced by alternative plasticizers (APs). Up to this date, urine was the sole matrix studied for plasticizer exposure in neonates hospitalized in the neonatal intensive care unit (NICU), a population highly vulnerable to toxic effects of plasticizers. The primary aim of this study was to assess simultaneous measurement of phthalate and AP metabolites in neonatal scalp hair. In addition, we aimed to use this matrix to investigate exposure of premature neonates to plasticizers during their stay in the NICU. Hair samples in this study were collected from premature neonates and their mothers included in a prospective birth cohort study in a tertiary NICU at the Antwerp University Hospital (UZA), Belgium. Samples from premature neonates (n = 45) and their mothers (n = 107) as well as from control neonates (n = 24) and mothers (n = 29) were analyzed using liquid-chromatography coupled to tandem mass spectrometry. This is the first study reporting metabolites of phthalate and alternative plasticizers in neonatal hair samples as biomarkers for exposure to these plasticizers. Results showed that hair sampled from premature neonates after a NICU stay contained significantly higher metabolite concentrations of both phthalates (DEHP, DiBP, and DnBP; 9.0-2500, 9.3-2200, and 24.7-5300 ng/g), and alternative plasticizers (DEHA, DEHT, and TOTM; 38.8-3400, 127.5-5700, and 10.8-8700 ng/g) - when compared to healthy control neonates. Besides, DEHP and DEHT metabolite concentrations were significantly higher than in hair sampled from adult populations. In addition, prolonged NICU exposure to non-invasive respiratory support devices and gastric tubes was correlated with increased concentrations in hair samples, indicating accumulation of plasticizers in this alternative matrix. In conclusion, our data indicate that preterm neonates are still highly exposed to phthalate and alternative plasticizers during NICU stay, despite the EU Medical Devices Regulation.

Effect of erythrophagocytosis-induced ferroptosis during angiogenesis in atherosclerotic plaques.

Intraplaque (IP) angiogenesis is a key feature of advanced atherosclerotic plaques. Because IP vessels are fragile and leaky, erythrocytes are released and phagocytosed by macrophages (erythrophagocytosis), which leads to high intracellular iron content, lipid peroxidation and cell death. In vitro experiments showed that erythrophagocytosis by macrophages induced non-canonical ferroptosis, an emerging type of regulated necrosis that may contribute to plaque destabilization. Erythrophagocytosis-induced ferroptosis was accompanied by increased expression of heme-oxygenase 1 and ferritin, and could be blocked by co-treatment with third generation ferroptosis inhibitor UAMC-3203. Both heme-oxygenase 1 and ferritin were also expressed in erythrocyte-rich regions of carotid plaques from ApoE-/- Fbn1C1039G+/- mice, a model of advanced atherosclerosis with IP angiogenesis. The effect of UAMC-3203 (12.35 mg/kg/day) on atherosclerosis was evaluated in ApoE-/- Fbn1C1039G+/- mice fed a western-type diet (WD) for 12 weeks (n = 13 mice/group) or 20 weeks (n = 16-21 mice/group) to distinguish between plaques without and with established IP angiogenesis, respectively. A significant decrease in carotid plaque thickness was observed after 20 weeks WD (87 ± 19 µm vs. 166 ± 20 µm, p = 0.006), particularly in plaques with confirmed IP angiogenesis or hemorrhage (108 ± 35 µm vs. 322 ± 40 µm, p = 0.004). This effect was accompanied by decreased IP heme-oxygenase 1 and ferritin expression. UAMC-3203 did not affect carotid plaques after 12 weeks WD or plaques in the aorta, which typically do not develop IP angiogenesis. Altogether, erythrophagocytosis-induced ferroptosis during IP angiogenesis leads to larger atherosclerotic plaques, an effect that can be prevented by ferroptosis inhibitor UAMC-3203.

Antegrade administration of mitomycin gel for upper tract urothelial carcinoma via percutaneous nephrostomy tube: a multi-institutional retrospective cohort study.

OBJECTIVES: To assess the safety profile of antegrade mitomycin gel instillation through a percutaneous nephrostomy tube (PCNT) for upper tract urothelial carcinoma (UTUC) with the aim of decreasing morbidity associated with therapy. PATIENTS AND METHODS: Patients undergoing antegrade administration of mitomycin gel via PCNT were retrospectively included for analysis from four tertiary referral centres between 2020 and 2022. The primary outcome was safety profile, as graded by Common Terminology Criteria for Adverse Events (v5.0). Post-therapy disease burden was assessed by primary disease evaluation (PDE) via ureteroscopy. RESULTS: Thirty-two patients received at least one dose of mitomycin gel via PCNT for UTUC, 29 of whom completed induction and underwent PDE. Thirteen patients (41%) had residual tumour present prior to induction therapy. At a median of 15.0 months following first dose of induction therapy, ureteric stenosis occurred in three patients (9%), all of whom were treated without later recurrence or chronic stenosis. Other adverse events included fatigue (27%), flank pain (19%), urinary tract infection (12%), sepsis (8%) and haematuria (8%). No patients had impaired renal function during follow-up and there were no treatment-related deaths. Seventeen patients (59%) had no evidence of disease at PDE and have not experienced recurrence at a median follow-up of 13.0 months post induction. CONCLUSIONS: Administration of mitomycin gel via a PCNT offers a low rate of ureteric stenosis, demonstrates a favourable safety profile, and is administered without general anaesthesia.

Evaluating the impact of COVID-19 countermeasures on alcohol consumption through wastewater-based epidemiology: A case study in Belgium.

Wastewater-based epidemiology (WBE) is a complementary approach to monitor alcohol consumption in the general population. This method measures concentrations of xenobiotic biomarkers (e.g., ethyl sulphate) in influent wastewater (IWW) and converts these to population-normalized mass loads (PNML, in g/day/1000 inhabitants) by multiplying with the flow rate and dividing by the catchment population. The aims of this case study were to: (i) investigate temporal trends in alcohol use during the COVID-19 pandemic; and (ii) measure the effect of policy measures on alcohol consumption. Daily 24-h composite IWW samples (n = 735) were collected in the wastewater treatment plant of the university city of Leuven (Belgium) starting from September 2019 to September 2021. This is the first study that investigates alcohol use through WBE for a continuous period of two years on a daily basis. Mobile phone data was used to accurately capture population fluxes in the catchment area. Data was evaluated using a time series based statistical framework to graphically and quantitatively assess temporal differences in the measured PNML. Different WBE studies observed temporal changes in alcohol use during the COVID-19 pandemic. In this study, the PNML of ethyl sulphate decreased during the first lockdown phase, potentially indicating that less alcohol was consumed at the Leuven area during home confinement. Contrastingly, alcohol use increased after the re-opening of the catering industry. Additionally, a decrease in alcohol use was observed during the exam periods at the University of Leuven and an increase during the holiday periods. The present study shows the potential of WBE to rapidly assess the impact of some policy measures on alcohol consumption in Belgium. This study also indicates that WBE could be employed as a complementary data source to fill in some of the current knowledge gaps linked to lifestyle behavior.

Targeting ferroptosis protects against experimental (multi)organ dysfunction and death.

The most common cause of death in the intensive care unit (ICU) is the development of multiorgan dysfunction syndrome (MODS). Besides life-supporting treatments, no cure exists, and its mechanisms are still poorly understood. Catalytic iron is associated with ICU mortality and is known to cause free radical-mediated cellular toxicity. It is thought to induce excessive lipid peroxidation, the main characteristic of an iron-dependent type of cell death conceptualized as ferroptosis. Here we show that the severity of multiorgan dysfunction and the probability of death are indeed associated with plasma catalytic iron and lipid peroxidation. Transgenic approaches underscore the role of ferroptosis in iron-induced multiorgan dysfunction. Blocking lipid peroxidation with our highly soluble ferrostatin-analogue protects mice from injury and death in experimental non-septic multiorgan dysfunction, but not in sepsis-induced multiorgan dysfunction. The limitations of the experimental mice models to mimic the complexity of clinical MODS warrant further preclinical testing. In conclusion, our data suggest ferroptosis targeting as possible treatment option for a stratifiable subset of MODS patients.

Development of an analytical method based on solid-phase extraction and LC-MS/MS for the monitoring of current-use pesticides and their metabolites in human urine.

Pyrethroids, organophosphorus pesticides and fipronil have been listed as priority chemicals in human biomonitoring studies because of their wide use and potential health effects in humans. The determination of 13 pesticides, including pyrethroids (deltamethrin, cypermethrin, permethrin, cyfluthrin, bifenthrin), organophosphorus (chlorpyrifos, chlorpyrifos-methyl, and malathion), fipronil, neonicotinoids (imidacloprid, acetamiprid and thiacloprid) and triazole (prothioconazole), together with 13 corresponding metabolites in human urine samples was achieved by solid-phase extraction and analysis by liquid chromatography coupled to tandem mass spectrometry. All targeted compounds, except malathion dicarboxylic acid, were measured with a mean within-accuracy (n = 5) of 71%-114% (RSD: 1%-14%) and between-run (n = 15) accuracy of 80%-118% (RSD: 2%-14%). Limits of quantitation of the targeted analytes ranged from 0.1 to 16 pg/mL. The detection result of urine samples from 25 volunteers indicated that the detection frequencies of 3,5,6-trichloro-2-pyridinol (median: 448 pg/mL), 6-chloropyridine-3-carboxylic acid (median: 193 pg/mL), 2-methyl-3-phenylbenzoic acid (median: 181 pg/mL), 3-phenoxybenzoic acid (median: 99 pg/mL), 2-isopropyl-6-methyl-4-pyrimidinol (median: 77 pg/mL), cyfluthrin (median: 59 pg/mL), cis-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylic acid (cis-DCCA, median: 53 pg/mL), trans-DCCA (median: 25 pg/mL), prothioconazole (median: 21 pg/mL), imidacloprid (median: 7 pg/mL), and prothioconazole-desthio (median: 1 pg/mL) were > 50%. The obtained results show that the validated method is suitable for the human biomonitoring of these current-use pesticides and their metabolites.

Anesthetic Considerations for Patients on Psychotropic Drug Therapies.

Psychotropic drugs are used in the treatment of psychiatric and non-psychiatric conditions. Many patients who are on psychotropic medications may present for procedures requiring anesthesia. Psychotropic medications can have dangerous interactions with drugs commonly used in anesthesia, some of which can be life-threatening. In this review, we describe the current anesthetic considerations for patients on psychotropic drug therapies, including antidepressants, antipsychotics, mood stabilizers, anxiolytics, and stimulants. The pharmacology, side effects, and potential drug interactions of the commonly prescribed psychotropic drug therapies with anesthetic agents are described. Further, we highlight the current recommendations regarding the cessation and continuation of these medications during the perioperative period.

Antisynthetase Syndrome with Severe Interstitial Lung Disease in Pregnancy.

Antisynthetase syndrome is a rare multisystem autoimmune disorder which clinically manifests with myositis, arthritis, interstitial lung disease, Raynaud phenomenon, and skin hyperkeratosis. Lung involvement represents the most severe form of disease and has rarely been reported in pregnancy. We present the case of a 22-year-old woman with antisynthetase syndrome and severe restrictive pulmonary disease who experienced a successful pregnancy and delivery. We discuss anesthetic considerations and highlight the importance of a multidisciplinary team approach in caring for parturients with multifactorial medical conditions.

Feasibility study on the use of elemental profiles to authenticate aromatic rice: the case of Basmati and Thai rice.

Among the thousands of existing rice varieties, aromatic rice has increasingly attracted consumer's preference in recent years. Within aromatic rice, Basmati, cultivated in some regions in Pakistan and India, is highly demanded. Other aromatic rice, cultivated in specific regions, for instance in Thailand (commonly referred to as Jasmine Thai rice), are also highly appreciated by consumers. In this work, the elemental profiles of commercially available rice samples (17 Basmati, 11 Thai, and 7 Long Grain rice) were determined by energy-dispersive X-ray fluorescence (ED-XRF) spectroscopy. The mass fractions of P, Cl, S, K, Fe, Cu, and Zn were significantly different (95% confidence interval) between Basmati and Thai rice and between Thai and Long Grain rice; only Cl, S, and Zn were significantly different between Basmati and Long Grain rice. Multivariate evaluation of the results combining soft independent modelling by class analogy (SIMCA) and partial least square discriminant analysis (PLS-DA) allowed the correct classification (true positives) of 94.1, 85.6, and 100% of the Basmati, Long Grain, and Thai rice, respectively. The specificity (true negatives) of Basmati, Long Grain, and Thai was 94.4, 82.1, and 100%, respectively.

Are the elemental fingerprints of organic and conventional food different? ED-XRF as screening technique.

Research has been conducted the last years to assess whether organically grown food is chemically different from produce of conventional agriculture and which markers are appropriate to discriminate between them. Most articles focus on one single food commodity, produced under strict controlled organic farming conditions, leaving open the question whether the difference would be seen when applied to the same commodity under different growing conditions. In this work 118 organic and 151 conventional samples of commercially available paprika powder, cinnamon, coffee, tea, chocolate, rice, wheat flour, cane sugar, coconut water, honey and bovine milk were characterised for their elemental composition using energy dispersive X-ray fluorescence. Resulting profiles were analysed using univariate and multivariate statistical techniques. Organic samples of a given commodity clustered together and were separated from their conventional counterparts. Differences in the elemental composition of food, could be used to develop statistical models for verifying the agronomical production system.

Application of wastewater-based epidemiology to investigate stimulant drug, alcohol and tobacco use in Lithuanian communities.

WBE was applied to evaluate illicit drug (i.e. amphetamine, cocaine, MDMA and methamphetamine), alcohol and tobacco use in three Lithuanian cities in 2018 and 2019. Considerable concentrations of methamphetamine and MDMA were found in the three locations, suggesting a specific Lithuanian consumption pattern. Yet, unexpected high concentrations of amphetamine (>4 µg/L) were detected in two samples of Kaunas in 2018. Through the use of chiral analysis and non-target and suspect drug precursor compound screening, these extreme values were confirmed to be the result of direct disposal of amphetamine in the sewers. Furthermore, substantial alcohol use was measured in the three investigated catchment populations of Lithuania with almost 4 standard drinks/day/inhabitant aged 15+ on average in 2019. For tobacco, an average of 5.6 cigarettes/day/inhabitant aged 15+ in 2019 was reported with large discrepancies between WBE figures and sales data, potentially highlighting illegal trade of tobacco products.

Authentication of PDO paprika powder (Pimentón de la Vera) by multivariate analysis of the elemental fingerprint determined by ED-XRF. A feasibility study.

Products with a Protected Denomination of Origin (PDO) are vulnerable to misdescription of their true geographical origin. In this work a method has been developed that allows the authentication of La Vera paprika powder (Pimentón de la Vera), a PDO product from the central-west Spanish region, Extremadura. The mass fractions of Br, Ca, Cr, Cl, Cu, Fe, K, Mn, Ni, P, Rb, S, Sr and Zn determined by energy dispersive X-ray fluorescence (ED-XRF) are used for classification purposes by multivariate analysis using Soft Independent Modelling of Class Analogy (SIMCA) (PCA-Class) and Partial Least Square-Discriminant Analysis (PLS-DA). Sixty-seven paprika samples purchased in supermarkets around Europe and on-line via the official web-site of Pimentón de La Vera, were used to build up the models for prediction purposes. The PCA-class model of La Vera paprika powder had a sensitivity of 82%, a specificity of 100% and an accuracy of 91%, whereas the PLS-DA model had a sensitivity of 100%, a specificity of 91% and an accuracy of 96%.

Stability of phosphatidylethanol 16:0/18:1 in authentic and spiked whole blood.

Phosphatidylethanol 16:0/18:1 (PEth) is the most abundant homologue of the phosphatidylethanol group of phospholipids. Formed only in the presence of ethanol, PEth is used as a biomarker in whole blood to provide information about the consumption of alcohol. As information on the storage life of PEth is essential for its beneficial use as a biomarker, this study investigated the stability of PEth in spiked and authentic whole blood samples stored at 4°C. Human whole blood samples (n = 23) and spiked whole blood samples (n = 7) with a concentration range between 5 and 2000 ng/ml were analysed at specific time intervals, up to 90 days. Differences were evident between the stability of authentic and spiked samples. PEth was stable at 4°C for 60 days (concentrations within 15% of initial concentration) in authentic samples, whereas spiked samples were stable for up to 30 days. This study emphasizes the importance of including authentic samples in stability experiments.

Use of elemental profiles to verify geographical origin and botanical variety of Spanish honeys with a protected denomination of origin.

Honey with Protected Denomination of Origin (PDO) could be an attractive target for fraudsters. Elemental profiles by Energy Dispersive-X Ray Fluorescence were processed by multivariate methods to classify 183 PDO honeys produced in three regions of Spain (Liébana, Granada, Tenerife). Additional honey samples (18) produced in a fourth region without PDO (El Bierzo) separated well from the PDO clusters. The manganese content was a discriminant marker of Liébana PDO and El Bierzo, that could also be differentiated from each other. Within each region, distinct clusters revealed differences between dark vs light varieties, multi- vs uni-floral honey and producers of the same PDO. The developed models were validated with 131 samples produced outside the PDO regions and El Bierzo. The proposed classification approach could be implemented as a fast screening tool to support pollen analysis in honey authentication. The reduced number of observations in some light honey models affected their performance.

Peripheral Nerve Blockade with Combined Standard and Liposomal Bupivacaine in Major Lower-Extremity Amputation.

BACKGROUND AND OBJECTIVES: Optimizing perioperative analgesia for patients undergoing major lower-extremity amputation remains a considerable challenge. The utility of liposomal bupivacaine as a component of peripheral nerve blockade for lower-extremity amputation is unknown. METHODS: We conducted an observational study comparing three different perioperative analgesic techniques for adults undergoing major lower-extremity amputation under general anesthesia between 2012 and 2017 at an academic medical center: (1) no regional anesthesia, (2) peripheral nerve blockade with standard bupivacaine, and (3) peripheral nerve blockade with a mixture of standard and liposomal bupivacaine. The primary outcome of cumulative opioid oral morphine milligram equivalent utilization in the first 72 hours postoperatively was compared across groups utilizing multivariable linear regression. RESULTS: A total of 631 unique anesthetics were included for 578 unique patients, including 416 (66%) without regional anesthesia, 131 (21%) with peripheral nerve blockade with a mixture of standard and liposomal bupivacaine, and 84 (13%) with peripheral nerve blockade with standard bupivacaine alone. Cumulative morphine equivalents were lower in those receiving peripheral nerve blockade with combined standard and liposomal bupivacaine compared with those not receiving regional anesthesia (multiplicative increase 0.67; 95% CI 0.50 to 0.90; P = 0.007). There were no significant differences in opioid utilization between peripheral nerve blockade groups (P = 0.59). CONCLUSIONS: Peripheral nerve blockade is associated with reduced opioid requirements after lower-extremity amputation compared with general anesthesia alone. However, the incorporation of liposomal bupivacaine is not significantly different to blockade employing only standard bupivacaine.

Use of energy-dispersive X-ray fluorescence combined with chemometric modelling to classify honey according to botanical variety and geographical origin.

Honey is one of the food commodities most frequently affected by fraud. Although addition of extraneous sugars is the most common type of fraud, analytical methods are also needed to detect origin masking and misdescription of botanical variety. In this work, multivariate analysis of the content of certain macro- and trace elements, determined by energy-dispersive X-ray fluorescence (ED-XRF) without any type of sample treatment, were used to classify honeys according to botanical variety and geographical origin. Principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) were used to create classification models for nine different botanical varieties-orange, robinia, lavender, rosemary, thyme, lime, chestnut, eucalyptus and manuka-and seven different geographical origins-Italy, Romania, Spain, Portugal, France, Hungary and New Zealand. Although characterised by 100% sensitivity, PCA models lacked specificity. The PLS-DA models constructed for specific combinations of botanical variety-country (BV-C) allowed the successful classification of honey samples, which was verified by external validation samples. Graphical abstract.

Heterochromia of the Hair and Eyelashes with Blaschkoid Dyspigmentation.

Heterochromia of the hair involves the presence of two distinctive colors of scalp hair in one individual. We report the case of a 4-year-old girl with reddish streaks of scalp hair, heterochromia of the eyelashes, and cutaneous hypopigmentation following the lines of Blaschko.

Malingering Imposed on Another: A Diagnosis That is Missing in Action?

BACKGROUND: Descriptions of malingering imposed on another, in which an individual induces or exaggerates symptoms in another for secondary gain (including financial benefit or access to medications), are remarkably scant in the current literature. We summarize reported cases of malingering imposed on another in order to underscore its relevance to practicing physicians. OBJECTIVE: We sought to review the available literature describing the creation or exaggeration of symptoms of illness, motivated by secondary gain, in another vulnerable individual. METHOD: A search of the literature using PubMed was undertaken searching the terms "malingering," "by proxy," and "imposed on another." RESULTS: Malingering imposed on another may be under-reported in the professional literature. Maintaining awareness that caregivers may misrepresent or embellish the symptoms of the identified patient for their own gain is an important consideration to forestall unnecessary testing, hospital admission, and exposure to adverse effects of treatments.