TMS 2023 BACK TO BUSINESS AT TMS2023

With nearly 4,500 attendees gathered in San Diego CA, the TMS 2023 Annual Meeting & Exhibition (TMS2023) was the fourth best-attended meeting in TMS history, marking a return to business as usual (more or less) after two decidedly unusual years for the Society's biggest event. By comparison, approximately 2,600 individuals came together in person for TMS2022 in Anaheim CA. One year earlier, TMS2021--held as a fully virtual conference--attracted 2,967 attendees from around the world. This year's event, held Mar 19-23 in one of TMS's most popular meeting locations, brought the conference back closer to its pre-COVID participation numbers. The last time TMS met in San Diego was in 2020 (shortly before widespread pandemic shutdowns began) when more than 4,600 individuals came together for the largest meeting in the Society's history.

Three-Stage Power Supply System Model for a Wearable IoT Device for COVID-19 Patients.

During the current crisis caused by the COVID-19 pandemic, Wearable IoT (WIoT) health devices have become essential resources for remote monitoring of the main physiological signs affected by this disease. As well as sensors, microprocessor, and wireless communication elements are widely studied, the power supply unit has the same importance for the WIoT technology, since the autonomy of the system between recharges is of great importance. This letter presents the design of the power supply system of a WIoT device capable of monitoring oxygen saturation and body temperature, sending the collected data to an IoT platform. The supply system is based on a three-stage block consisting of a rechargeable battery, battery charge controller, and dc voltage converter. The power supply system is designed and implemented as a prototype in order to test performance and efficiency. The results show that the designed block provides a stable supply voltage avoiding energy losses, which makes it an efficient and rapidly developing system.

An Update on the United Downs Geothermal Power Project, Cornwall, UK

The United Downs geothermal power project has been developed by Geothermal Engineering Ltd (GEL) and is the first geothermal electricity project in the UK. The site was selected in 2010 for its geology (strongly faulted, radiogenic granite), surface infrastructure, grid connection and potential community acceptance. The deep drilling programme started in 2018, with the production well drilled to 5,275 m MD and deviating from 3,390 m to a final inclination of 33.5º, representing the deepest onshore well in the UK. The injection well was then drilled to 2,393m MD, deviating from 1,020 m to a final inclination of 40º. The drilling of a deep production well and shallow injection well into a natural fault zone is a concept developed by GEL, based on some of the results from the research at the Hot Dry Rocks project in Rosemanowes, Cornwall. The production well has successfully encountered significant permeability horizons within the target fault zone, temperatures of 180ºC and world-class lithium concentrations. It is expected to provide between 2 and 3 MWe to the National Grid and carbon neutral heat to a proposed 6 km heat main and the project has been associated with many universities and pan European research projects. Despite the delays caused by the Covid-19 pandemic, the United Downs project has seen a number of exciting milestones since EGC 2019, including completion of drilling, extensive well testing/stimulation and signing of the first Power Purchase Agreement (PPA) for deep geothermal electricity in the UK with Ecotricity. The team also secured grant funding for a demonstration plant that will trial Direct Lithium Extraction (DLE) from the deep geothermal fluid. This paper presents an overview of the initial results of drilling and testing, briefly highlighting the success of hydraulic stimulation and management of induced seismicity during development. It also provides a forward look to the final stages of the United Downs development and the future of geothermal power projects across Cornwall. © 2022 Geothermal Resources Council. All rights reserved.

Exploration of DFT and TD-DFT computation to investigate the interaction between paracetamol and lithium or its compounds.

Paracetamol is a commonly used antipyretic drug and its consumption drastically was increased during the COVID-19 times as fever was one of the symptoms. The excessive usage of paracetamol could harm humans, as the unused accumulated paracetamol can involve in the reaction with many small molecules as well as can interact with several biomolecules. Lithium chloride in its hydrated form is used as an antimanic drug and a geroprotector. It is needed in very small quantities by humans. Tetrahydrated form of lithium ion is the most stable hydrated form. Herein, the authors have investigated the interaction of paracetamol with tetrahydrated lithium chloride (1:1 and 1:2) using the DFT and TD-DFT calculations at 298 K and 310 K. The interaction of paracetamol with lithium chloride P1 (1:1), P2 (2:1), P3 (3:1) and P4 (4:1) are also studied by DFT calculations in default and CPCM model. The authors have calculated the free energy, optimization energy, dipole moment and other thermodynamic parameters of all the systems. Based on enthalpy and change in Gibbs free energy, the interaction was maximum between the paracetamol and tetrahydrated lithium chloride at 298 K as well as 310 K which indicates that the hydrated lithium chloride is being consumed by unused paracetamol. In P1 and P3, lithium showed interaction with oxygen of phenolic group and other atoms of all the paracetamol molecules present, while in P2 and P4, lithium showed these interactions with only one paracetamol molecule.

Case report: Treatment-resistant depression, multiple trauma exposure and suicidality in an adolescent female with previously undiagnosed Autism Spectrum Disorder.

High rates of co-occurring depression are commonly reported in youth with Autism Spectrum Disorder (ASD), especially in individuals without intellectual disability (ID). Depression in ASD undermines adaptive behavior and is associated with a higher risk of suicidality. Females with ASD may be particularly vulnerable due to their greater use of camouflaging strategies. Indeed, in comparison to males, ASD is underdiagnosed in females, despite higher rates of internalizing symptoms and suicidality. Trauma exposure may also play a role in the development of depressive symptoms in this population. Moreover, evidence for effective treatments of depression in autistic youth are lacking, with ASD individuals frequently experiencing low efficacy and side effects. We present the case of an adolescent female with previously undiagnosed ASD without ID, admitted for active suicidal plans and a treatment-resistant depression (TRD), occurred after a COVID-19 lockdown in the context of cumulative exposure to stressful life events. Comprehensive clinical assessments performed at intake confirmed severe depression with suicidality. Intensive psychotherapy and different changes in medications were carried out (SSRI, SNRI, SNRI + NaSSA, SNRI + aripiprazole), all of which were ineffective, with persistent suicidal thoughts, often requiring intensive individual monitoring. The patient was finally successfully treated with lithium augmentation of fluoxetine, with no side effects. During hospitalization she was also evaluated by an ASD specialized center, where a diagnosis of ASD was made according to the Autism Diagnostic Observation Schedule (ADOS) and the Autism Diagnostic Interview-Revised (ADI-R) scores, as well as to clinical judgment of a senior psychiatrist. The present case report shows that clinicians should not overlook undiagnosed autism as a possible cause of TRD, especially in females without ID, where higher rates of under diagnosis may be in part related to their greater use of camouflage. It also suggests that ASD underdiagnosis and resulting unmet needs may be involved in vulnerability to stressful experiences, depression, and suicidality. Furthermore, it shows the complexity of providing care to TRD in youth with autism, suggesting that an augmentation therapy with lithium, a commonly recommended therapeutic strategy for refractory depression in typically developing samples, may also be effective in this population.

Latin American lithium in post-pandemic times

The Covid-19 pandemic represented a watershed in the dynamics of global socio- environmental change, consolidating the need to implement a new energy paradigm and electromobility as palliatives for the crisis unleashed by burning fossil fuels. Against this transforming scenario, extractive pressures on lithium reserves in the Global South increased. We hypothesize that the "Lithium Triangle" made up of the salt flats of Argentina, Bolivia and Chile, has given way to a "Latin American lithium-bearing quarry". Furthermore, the Lithium Triangle also witnesses the unfolding tensions between the Asian block and the Atlantic world, visible centrally in the dispute between the United States and China. China monopolized various lithium reserves in Latin America. Likewise, this picture is completed with a commitment by some nations (Bolivia, Chile, and Mexico) to create national public lithium companies and grow locally in lithium technology. With increasing pressure on lithium resources, under the prevailing "evaporite" technique, it is difficult to achieve the UN sustainable development goals related to land and water use. Methodologically, the research combines research data collected over a decade on the lithium debate, bibliographic review, statistics, interviews with key informants, and participant observation.

Asymmetric effects and volatility transmission from metals markets to solar energy stocks: Evidence from DCC, ADCC, and quantile regression approach

Detrimental environmental repercussions have recently given rise to an interest in green investments. Although solar energy stocks are appealing assets for ethical investors, little is known about their dynamic correlations and linkages with metal (silicon, lithium, and rare earth) markets, particularly during economic events which is essential for hedging effectiveness and asset allocation. This study investigates the nexus between metal markets, oil price volatility (OVX), market sentiments (VIX), and solar energy markets using DCC, ADCC models, and the quantile regression approach. The results show both symmetric and asymmetric shock spillover between metals markets, VIX, OVX, and solar energy markets which are more prominent during COVID-19 pandemic, US-China trade frictions, and Russian invasion of Ukraine. For portfolio management, the hedging effectiveness of lithium stocks is highest, followed by silicon and rare earth metals. However, the hedge ratios are time-varying, and the variability is highest during US-China trade frictions. The quantile regression estimates reveal that lithium market is the most persistent determinant of solar energy stocks followed by silicon market even after segregating the periods into Paris Agreement and COVID-19 pandemic. Thus, lithium and silicon are driving markets of solar energy markets and can be a cause of omitted variable bias if stay unobserved. Nonetheless, there is little influence of VIX, rare earth metals, and OVX on solar energy stocks. Lastly, the estimations of threshold regression suggest that market sentiments change the association between metal markets and solar energy markets after the VIX reaches a certain threshold level. © 2023

Analyze the Effects of COVID-19 on Energy Storage Systems: A Techno-Economic Approach

During the COVID-19 pandemic, the U.S. power sector witnessed remarkable electricity demand changes in many geographical regions. These changes were evident in population-dense cities. This paper incorporates a techno-economic analysis of energy storage systems (ESSs) to investigate the pandemic's influence on ESS development. In particular, we employ a linear program-based revenue maximization model to capture the revenues of ESS from participating in the electricity market, by performing arbitrage on the energy trading, and regulation market, by providing regulation services to stabilize the grid's frequency. We consider five dominant energy storage technologies in the U.S., namely, Lithium-ion, Advanced Lead Acid, Flywheel, Vanadium Redox Flow, and Lithium-Iron Phosphate storage technologies. Extensive numerical results conducted on the case of New York City (NYC) allow us to highlight the negative impact that COVID-19 had on the NYC power sector. © 2023 IEEE.

Lithium's antiviral effects: a potential drug for CoViD-19 disease?

BackgroundSince its introduction in modern medicine, naturalistic observations emerged about possible uses of lithium treatment for conditions different from recurring affective disorders, for which it is still a first-line treatment option. Some evidence about the antiviral properties of lithium began in the early 1970s, when some reports found a reduction of labial-herpetic recurrences. The present review aims to present most of the pre-clinical and clinical evidence about lithium's ability to inhibit DNA and RNA viruses, including Coronaviridae, as well as the possible pathways and mechanisms involved in such antiviral activity.Main bodyDespite a broad number of in vitro studies, the rationale for the antiviral activity of lithium failed to translate into methodologically sound clinical studies demonstrating its antiviral efficacy. In addition, the tolerability of lithium as an antiviral agent should be addressed. In fact, treatment with lithium requires continuous monitoring of its serum levels in order to prevent acute toxicity and long-term side effects, most notably affecting the kidney and thyroid. Yet lithium reaches heterogeneous but bioequivalent concentrations in different tissues, and the anatomical compartment of the viral infection might underpin a different, lower need for tolerability concerns which need to be addressed.ConclusionsLithium presents a clear antiviral activity demonstrated at preclinical level, but that remains to be confirmed in clinical settings. In addition, the pleiotropic mechanisms of action of lithium may provide an insight for its possible use as antiviral agent targeting specific pathways.

COVID-19: From the Molecular Mechanisms to Treatment

The 2019 novel coronavirus (SARS-CoV-2) causes severe pneumonia called COVID-19 and leads to severe acute respiratory syndrome with a high mortality rate. The SARS-CoV-2 virus in the human body leads to jumpstarting immune reactions and multi-organ inflammation, which has poorer outcomes in the presence of predisposing conditions, including hypertension, dyslipidemia, dysglycemia, abnormal adiposity, and even endothelial dysfunction via biomolecular mechanisms. In addition, leucopenia, hypoxemia, and high levels of both cytokines and chemokines in the acute phase of this disease, as well as some abnormalities in chest CT images, were reported in most patients. The spike protein in SARS-CoV-2, the primary cell surface protein, helps the virus anchor and enter the human host cells. Additionally, new mutations have mainly happened for spike protein, which has promoted the infection's transmissibility and severity, which may influence manufactured vaccines' efficacy. The exact mechanisms of the pathogenesis, besides molecular aspects of COVID-19 related to the disease stages, are not well known. The altered molecular functions in the case of immune responses, including T CD4+, CD8+, and NK cells, besides the overactivity in other components and outstanding factors in cytokines like interleukin-2, were involved in severe cases of SARS-CoV-2. Accordingly, it is highly needed to identify the SARS-CoV-2 bio-molecular characteristics to help identify the pathogenesis of COVID-19. This study aimed to investigate the bio-molecular aspects of SARS-CoV-2 infection, focusing on novel SARS-CoV-2 variants and their effects on vaccine efficacy.Copyright © 2022 NRITLD, National Research Institute of Tuberculosis and Lung Disease, Iran.

The Paradox of Green Growth: Challenges and Opportunities in Decarbonizing the Lithium-Ion Supply Chain

Global decarbonization is a megatrend destined to impact multiple sectors of the economy. The commodity sector in particular looks set to benefit, given the acute need for raw materials to feed the energy transition. This global transition will take decades and while an "all of the above” energy policy will be necessary, the lithium-ion battery promises to play a central role in the decarbonization of the transportation and grid scale energy storage sectors. With lithium-ion battery costs falling steadily since the early 1990s, many believe that the technology promises to become even more ubiquitous, helping to electrify the global economy. Recent exogenous shocks such as the US-China trade war, COVID-19, and the Russian invasion of Ukraine have underlined the fragility of global energy supply chains and the need for a resilient global energy infrastructure. While solutions to the exogenous shocks seem straightforward, there is an increasingly evident paradox. To achieve significant decarbonization and electrification goals, more, not fewer, battery raw materials will be required and the energy used to produce these materials will almost certainly originate from fossil fuels, possibly slowing the decline of the carbon intensity of industry. Innovation along the supply chain is the only realistic way to achieve large-scale decarbonization. This will require R&D, necessitating a coordinated response between the public and private sector as supply chains evolve. This chapter looks at the geopolitical, economic, technological, and legislative challenges and opportunities that green growth presents in the lithium-ion battery ecosystem as the industry embarks on a rapid growth phase. © 2023, The Author(s), under exclusive license to Springer Nature Switzerland AG.

The Thyroid Pathologist Meets Therapeutic Pharmacology.

The effects of many pharmacological agents on thyroid function are well known. Direct influences on measurements of thyroid function tests are also described. However, certain classes of drugs produce morphological changes in the gland. This review focuses on the significance of the following drug classes for the thyroid pathologist: iodine, antithyroid drugs, psychotropic drugs, antibiotics, cardiotropic drugs, antidiabetic drugs, and immunomodulatory agents. Radioactive iodine initially induces mild histologic changes; however, the long-term effects include marked follicular atrophy, fibrosis, and nuclear atypia-changes that vary depending on the pre-therapy condition of the gland. Some psychotropic drugs have been associated with a spectrum of inflammatory changes throughout the gland. The tetracycline class of antibiotics, namely minocycline, can lead to a grossly black thyroid gland with pigment seen in both colloid and follicular epithelial cells while variably present within thyroid nodules. The surgical pathologist most commonly sees an amiodarone-affected gland removed for hyperthyroidism, and the histologic findings again depend on the pre-therapy condition of the gland. While GLP-1 receptor agonists carry an FDA black box warning for patients with a personal or family history of multiple endocrine neoplasia or medullary thyroid carcinoma, the C cell hyperplasia originally noted in rats has not borne out in human studies. Finally, thyroiditis and hypothyroidism are well known complications of checkpoint inhibitor therapy, and rare cases of severe thyroiditis requiring urgent thyroidectomy have been reported with unique histologic findings. In this review, we describe the histologic findings for these drugs and more, in many cases including their functional consequences.

Nickel-Ion Activating Discarded COVID-19 Medical Surgical Masks for Forming Carbon-Nickel Composite Nanowires and Using as a High-Performance Lithium Battery Anode

With the prevalence of COVID-19, wearing medical surgical masks has become a requisite measure to protect against the invasion of the virus. Therefore, a huge amount of discarded medical surgical masks will be produced, which will become a potential hazard to pollute the environment and endanger the health of organisms without our awareness. Herein, a green and cost-effective way for the reasonable disposal of waste masks becomes necessary. In this work, we realized the transformation from waste medical surgical masks into high-quality carbon-nickel composite nanowires, which not only benefit the protection of the environment and ecosystem but also contribute to the realization of economic value. The obtained composite carbon-based materials demonstrate 70 S m-1conductivity, 5.2 nm average pore diameters, 234 m2g-1surface areas, and proper graphitization degree. As an anode material for lithium-ion batteries, the prepared carbon composite materials demonstrate a specific capacity of 420 mA h g-1after 800 cycles at a current density of 0.2 A g-1. It also displays good rate performance and decent cycling stability. Therefore, this study provides an approach to converting the discarded medical surgical masks into high-quality carbon nanowire anode materials to turn waste into treasure. © 2023 American Chemical Society. All rights reserved.

Fluoxetine plus lithium for treatment of mental health impairment in Long Covid.

Purposes: (1) To summarize the mental conditions that may accompany persistent symptoms following acute infection by SARS-CoV-2, often termed Long Covid; (2) to formulate treatment based upon the brain cells that are dominantly affected. Methods: (1) Review the reports relating to the mental symptoms occurring in Long Covid. (2) Review the drugs that address the brain cells affected in Long Covid, and suggest pharmacotherapy for those patients whose response to psychotherapy is suboptimal. Results: Long Covid affects ~ 10% of patients infected by SARS-CoV-2, and mental symptoms affect ~ 20% of persons with Long Covid. The brain cell-types that have been demonstrated as dominantly affected in Long Covid are astrocytes, oligodendrocytes, neurons, endothelial cells/pericytes, and microglia. Lithium and fluoxetine each address all of those four cell-types. Low dosage of each is likely to be well-tolerated and to cause neither clinically important adverse events (AE) nor serious adverse events (SAE). Conclusion: For those patients whose response to psychotherapy is suboptimal, lithium and fluoxetine should be administered in combination for both depth of benefit and reduction of dosages.

Sr(II) and Ba(II) Alkaline Earth Metal-Organic Frameworks (AE-MOFs) for Selective Gas Adsorption, Energy Storage, and Environmental Application.

Two new alkaline earth metal-organic frameworks (AE-MOFs) containing Sr(II) (UPJS-15) or Ba(II) (UPJS-16) cations and extended tetrahedral linker (MTA) were synthesized and characterized in detail (UPJS stands for University of Pavol Jozef Safarik). Single-crystal X-ray analysis (SC-XRD) revealed that the materials are isostructural and, in their frameworks, one-dimensional channels are present with the size of ~11 × 10 Å2. The activation process of the compounds was studied by the combination of in situ heating infrared spectroscopy (IR), thermal analysis (TA) and in situ high-energy powder X-ray diffraction (HE-PXRD), which confirmed the stability of compounds after desolvation. The prepared compounds were investigated as adsorbents of different gases (Ar, N2, CO2, and H2). Nitrogen and argon adsorption measurements showed that UPJS-15 has SBET area of 1321 m2 g-1 (Ar) / 1250 m2 g-1 (N2), and UPJS-16 does not adsorb mentioned gases. From the environmental application, the materials were studied as CO2 adsorbents, and both compounds adsorb CO2 with a maximum capacity of 22.4 wt.% @ 0 °C; 14.7 wt.% @ 20 °C and 101 kPa for UPJS-15 and 11.5 wt.% @ 0°C; 8.4 wt.% @ 20 °C and 101 kPa for UPJS-16. According to IAST calculations, UPJS-16 shows high selectivity (50 for CO2/N2 10:90 mixture and 455 for CO2/N2 50:50 mixture) and can be applied as CO2 adsorbent from the atmosphere even at low pressures. The increased affinity of materials for CO2 was also studied by DFT modelling, which revealed that the primary adsorption sites are coordinatively unsaturated sites on metal ions, azo bonds, and phenyl rings within the MTA linker. Regarding energy storage, the materials were studied as hydrogen adsorbents, but the materials showed low H2 adsorption properties: 0.19 wt.% for UPJS-15 and 0.04 wt.% for UPJS-16 @ -196 °C and 101 kPa. The enhanced CO2/H2 selectivity could be used to scavenge carbon dioxide from hydrogen in WGS and DSR reactions. The second method of applying samples in the area of energy storage was the use of UPJS-15 as an additive in a lithium-sulfur battery. Cyclic performance at a cycling rate of 0.2 C showed an initial discharge capacity of 337 mAh g-1, which decreased smoothly to 235 mAh g-1 after 100 charge/discharge cycles.

Current Situation and Trend of Electric Vehicle Battery Business - Take CATL as an example

New energy vehicles are one of the most important strategic emerging industries in China. Lithium battery is the universal choice of energy supply for new energy vehicles at present, which has the advantage of security and stability compared with other new energy sources. China has a complete lithium battery industry chain from lithium mining to battery manufacturing. The CATL is one of the large enterprises of this chain. However, with the rise of domestic competitors, foreign enterprises such as LG Chem have entered the Chinese market strongly. The intensification of market competition and the possible adjustment of national policies make the development of CATL facing many challenges. As early as before the COVID-19, the profits of CATL had declined, and the research on the strategic development of CATL has important practical significance. This paper analyzes the advantages and disadvantages, opportunities and threats faced by the power battery business of CATL through the SWOT analysis model. Based on the analysis of the development strategic direction corresponding to the combination of the four elements of the internal and external environment in the model, it is concluded that under the background of the emerging new energy vehicle industry and the gradual improvement of the market, CATL should seek diversified development strategic direction (ST strategy). [ FROM AUTHOR]

Total synthesis of antiviral drug, nirmatrelvir (PF-07321332).

The emergence and rapid spread of coronavirus disease 2019 (COVID-19), a potentially fatal disease, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has swiftly led to public health crisis worldwide. Hence vaccines and antiviral therapeutics are an important part of the healthcare response to combat the ongoing threat by COVID-19. Here, we report an efficient synthesis of nirmatrelvir (PF-07321332), an orally active SARS-CoV-2 main protease inhibitor.

A novel approach to monitoring lithium blood levels and renal function in patients receiving lithium during the COVID-19 pandemic

Introduction: Lithium is commonly administered to patients in an outpatient department (OPD) setting. Regular monitoring of lithium levels and renal function in accordance with published guidelines is required. In our unit, this is usually performed at OPD review. During the COVID-19 pandemic, reviews were either postponed or done remotely. Objective(s): 1. To devise a system to ensure that patients receiving lithium had appropriate blood test monitoring in the absence of traditional OPD appointments. 2. To assess the efficacy of this intervention by recording blood test dates and comparing with pre-COVID compliance. Method(s): All outpatients receiving lithium, identified from the hospital database, received (1) a letter summarising the monitoring guidelines and (2) prospectively dated blood request forms. Patients at higher risk of contracting COVID-19 were advised to attend their primary care setting. Others were encouraged to attend primary care or our phlebotomy department. Compliance was measured by accessing the hospital's laboratory enquiry computer based system and compared with pre-COVID-19 figures. Information was anonymised, as per General Data Protection Regulations. Result(s): 57 patients receiving lithium were identified. Prior to the first Irish lockdown in March 2020, 16 (28%) were overdue testing. Three months into the pandemic, 15 patients (26%) were overdue testing. Conclusion(s): In the absence of routine outpatient appointments during the COVID-19 pandemic, the provision of written guidelines and completed blood request forms for patients receiving lithium was effective in ensuring monitoring of lithium levels and renal function. This system can be utilised as an alternative/adjunct to OPD review benefitting patients and health service delivery.

Clues to Bradycardia in a Psychiatric Patient can be Revealed by Good History-Taking: A Case Report and Literature Review.

Lithium is a medication commonly used as a mood stabilizer and can have numerous long-lasting side effects. In this case report, we aim to remind clinicians of such consequences. A 68-year-old woman with a psychiatric history presented for mild COVID-19 and developed sinus bradycardia. A permanent pacemaker was planned for her but was cancelled following good history-taking which revealed prior lithium use. The patient was found to have hyperparathyroidism and hypothyroidism, treatment of which resolved the bradycardia. This case serves to remind clinicians that history-taking remains of paramount importance as in this scenario of bradycardia in a psychiatric patient. An invasive therapeutic measure was precluded by good history-taking. There are several mechanisms by which hypothyroidism and hyperparathyroidism can induce bradycardia. COVID-19 infection can also induce bradycardia. LEARNING POINTS: Clinicians should suspect lithium as a cause in any psychiatric patient with new-onset bradycardia.Lithium can induce bradycardia either directly or even after discontinuation indirectly through hypothyroidism and/or hyperparathyroidism.Invasive measures can be avoided with adequate management of these endocrine issues.

Conservative Management of Acquired Tracheo-Esophageal Fistula after Lithium Button Battery Ingestion

Introduction:Acquired tracheo-esophageal fistula (TEF) is a dreaded complication of lithium button battery (LBB) ingestion in the pediatric population. Traditionally acquired TEFs are managed with surgical interventions. Very few case reports have described successful closure of a TEF secondary to LBB with conservative management. There is no reported literature on the use fibrin glue or laser therapy to enhance closure. Here we describe successful conversative management of TEF secondary to LBB and for the first time, attempted trial of fibrin glue and argon laser therapy. Case presentation: 13-month-old female presented to the emergency department with a 3-day history of croupy cough. Neck X ray demonstrated a radio-opaque foreign body suggestive of a button battery. Patient urgently underwent rigid esophagoscopy and found to have a 20 mm lithium battery in the proximal esophagus. The negative pole was facing anteriorly. Battery was retrieved and inspection revealed a Zagar 2 B grade mucosal injury. Site was washed with 0.25% acetic acid. Direct laryngoscopy and bronchoscopy noted significant posterior tracheal wall edema. Patient was kept NPO overnight and an esophagram obtained next day was reassuring. Therefore, diet was advanced as tolerated and patient discharged next day with plan to repeat esophagram in 2 weeks and endoscopy in 4 weeks. Patient presented 3 days later with drooling, coughing, nasal congestion. She tested positive for SARS Covid 19 PCR on admission. Esophagram at admission noted irregularity and distension of the proximal esophagus with persistent focal outpouching. Patient was kept strict NPO and a repeat esophagram 24 hours later showed large volume aspiration associated with excessive coughing. A nasogastric tube was placed, and tube feedings initiated. Esophogastroduodenoscopy (EGD) was delayed by 1 week due to COVID positive status and upper respiratory symptoms. Initial EGD demonstrated purulent exudates in proximal esophagus and a 6 mm fistulous opening surrounded by ulcerated margins. Bronchoscopy confirmed tracheal end of fistula in addition to posterior tracheal wall ulceration. A fiber-optic scope was used to advance the endotracheal tube so that its distal end was positioned beyond the inflamed mucosa. Patient was kept intubated and sedated, on IV antibiotics and PPI, and on NG tube feeds in the ICU. Repeat scope 7 days post TEF diagnosis showed a 4 mm fistula with healing of the ulcerated mucosa. Fibrin glue was injected into the fistula from the tracheal side in an attempt to close the TEF, but this was unsuccessful and lead to dislodgment of fibrin glue into airway creating a foreign body which necessitated endoscopic retrieval. EGD, 14 days after diagnosis of TEF demonstrated a fistula now ~ 3 mm wide. Argon plasma coagulation (APC) probe (Beamer unit flow of 0.5 L/min,15 W) was directed at the mucosa lining the esophageal end of the fistula with an aim to promote healing by secondary intention. At 21 days post TEF diagnosis complete closure of the fistula was demonstrated on EGD and bronchoscopy and the per-operative esophogram was reported as normal. Patient was discharged 5 days later tolerating an age-appropriate diet. A follow-up esophogram 2 weeks later was reassuring. Patient was asymptomatic on clinical follow up visit 4 weeks from discharge. Discussion(s): Acquired TEF secondary to LBB ingestion is traditionally managened through endoscopic or open surgical repair. However, these procedures can be complicated by high rates of recurrent laryngeal nerve injury, tracheal stenosis, recurrent fistula, and mortality. Thus, experts have started to advocate the use of esophageal rest as conservative management of acquired TEF to permit closure by secondary intention. Five pediatric cases to date have reported sustained closure of TEF secondary to LBB with conservative management including strict NPO status and tube feeds/parenteral nutrition. The duration of healing has varied from 4 -11 weeks. We documented successful healing of acquired TEF within 21 days of initial diagnosis making it the shortest recovery period to date. We report the use of argon plasma coagulation at low settings to produce controlled heat coagulation at the fistula site in order to expose the submucosa and enhance healing by secondary intention. Successful closure of congenital TEF have been reported with injection of fibrin glue into the fistulous tract but this technique may not work for acquired TEF because of surrounding inflammation and a patulous tract. We opted to keep our patient sedated and intubated for 2 weeks to minimize movement, and promote healing of the TEF, but risk vs benefit needs to be weighed on a case-to-case basis. In conclusion, conservative management of acquired TEF is a feasible first step and may be considered before opting for surgical repair. Use of APC at low setting may reduce duration of closure of acquired TEF but high-powered, multi-center studies are needed.