Human Case Reports Research Articles

Molecular prevalence of Dirofilaria sp. hongkongensis, among the dog population in Thiruvananthapuram, India

Human dirofilariasis is an emerging vector-borne zoonotic parasitic disease in India. Humans are accidental hosts. Symptomatic dirofilariasis, although uncommon is typically manifested in humans as pulmonary, ocular, or subcutaneous nodules. The present research reports the prevalence of the species, Dirofilaria sp. hongkongensis among the dog population in the Kani tribal settlements within the Agasthyamala Biosphere Reserve located at the southernmost end of the Western Ghats, Kerala. To study the prevalence, we conducted a random blood survey among the dog population in these tribal settlements in Thiruvananthapuram. Whole blood was collected from stray and domesticated animals. Genomic DNA was extracted and the microfilariae in the blood were characterized using the slide smear and COI-based marker specific to nematodes. After processing the data from the Sanger sequencer using BLAST, the sequences were submitted to GenBank. Over 25 % of dogs were found positive for Dirofilaria sp. hongkongensis, which is genetically identical to the strain causing human dirofilariasis as is shown by the phylogenetic analysis. The study reveals that the Kani tribes, who reside in deep forests, are particularly vulnerable to this strain of Dirofilaria sp. hongkongensis. Human case reports of this specific strain have been recorded in Kerala over the past decade. The effective elimination is ultimately impacted by a lack of knowledge regarding the mosquito vectors. Dirofilariasis in dogs and humans is on the rise, which demands both active disease surveillance and proper treatment.

Rickettsia africae infections in sub-Saharan Africa: A systematic literature review of epidemiological studies and summary of case reports.

Rickettsia africae is a tick-borne bacteria known to cause African tick bite fever (ATBF). While the disease was first described more than 100 years ago, knowledge of transmission risk factors and disease burden remain poorly described. To better understand the burden of R. africae, this article reviewed and summarized the published literature related to ATBF epidemiology and clinical management. Using a systematic approach, consistent with the PRISMA guidelines, we identified more than 100 eligible articles, including 65 epidemiological studies and 41 case reports. Most reports described R. africae in ticks and livestock, while human studies were less common. Human disease case reports were exclusively among returning travellers from non-endemic areas, which limits our disease knowledge among at-risk populations: people living in endemic regions. Substantial efforts to elucidate the ATBF risk factors and clinical manifestations among local populations are needed to develop effective preventative strategies and facilitate appropriate and timely diagnosis.

Thyroid Hyperplasia and Neoplasm Adverse Events Associated With Glucagon-Like Peptide-1 Receptor Agonists in the Food and Drug Administration Adverse Event Reporting System: Retrospective Analysis.

Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) are one of the most commonly used drugs for type 2 diabetes mellitus. Clinical guidelines recommend GLP-1 RAs as an adjunct to diabetes therapy in patients with chronic kidney disease, presence or risk of atherosclerotic cardiovascular disease, and obesity. The weight loss observed in clinical trials has been explored further in healthy individuals, putting GLP-1 RAs on track to be the next weight loss treatment. Although the adverse event profile is relatively safe, most GLP-1 RAs come with a labeled boxed warning for the risk of thyroid cancers, based on animal models and some postmarketing case reports in humans. Considering the increasing popularity of this drug class and its expansion into a new popular indication, a further review of the most recent postmarketing safety data was warranted to quantify thyroid hyperplasia and neoplasm instances. GLP-1 RA patient reports from the US Food and Drug Administration (FDA) Adverse Event Reporting System database were analyzed using reporting odds ratios and 95% CIs. In this study, we analyzed over 18 million reports from the US FDA Adverse Event Reporting System and provided evidence of significantly increased propensity for thyroid hyperplasias and neoplasms in patients taking GLP-1 RA monotherapy when compared to patients taking sodium-glucose cotransporter-2 (SGLT-2) inhibitor monotherapy. GLP-1 RAs, regardless of indication, are associated with an over 10-fold increase in thyroid neoplasm and hyperplasia adverse event reporting when compared to SGLT-2 inhibitors.

Dyslipidaemia management in pregnant patients: a 2024 update.

Over several decades, the approach to treating dyslipidaemias during pregnancy remains essentially unchanged. The lack of advancement in this field is mostly related to the fact that we lack clinical trials of pregnant patients both with available as well as new therapies. While there are numerous novel therapies developed for non-pregnant patients, there are still many limitations in dyslipidaemia treatment during pregnancy. Besides pharmacotherapy and careful clinical assessment, the initiation of behavioural modifications as well as pre-conception management is very important. Among the various lipid-lowering medications, bile acid sequestrants are the only ones officially approved for treating dyslipidaemia in pregnancy. Ezetimibe and fenofibrate can be considered if their benefits outweigh potential risks. Statins are still considered contraindicated, primarily due to animal studies and human case reports. However, recent systematic reviews and meta-analyses as well as data on familial hypercholesterolaemia (FH) in pregnant patients have indicated that their use may not be harmful and could even be beneficial in certain selected cases. This is especially relevant for pregnant patients at very high cardiovascular risk, such as those who have already experienced an acute cardiovascular event or have homozygous or severe forms of heterozygous FH. In these cases, the decision to continue therapy during pregnancy should weigh the potential risks of discontinuation. Bempedoic acid, olezarsen, evinacumab, evolocumab and alirocumab, and inclisiran are options to consider just before and after pregnancy is completed. In conclusion, decisions regarding lipid-lowering therapy for pregnant patients should be personalized. Despite the challenges in designing and conducting studies in pregnant women, there is a strong need to establish the safety and efficacy of dyslipidaemia treatment during pregnancy.

Native Australian Bronze Orange Stink Bug (Musgraveia sulciventris)–Related Corneal Injury

Abstract: The bronze orange stink bug (Musgraveia sulciventris) is an insect native to Australia that is found in citrus trees and gardens in coastal Queensland and New South Wales. The common name “stink bug” is attributed to the foul spray emitted from these insects when they are threatened. This spray can result in corneal injuries; however, human case reports of stink bug bodily fluid exposure to the eye are rare and have not been previously reported for this species. This report describes a case of the native Australian insect bronze orange stink bug causing irritant contact keratitis in the eye, which is the only reported case in the literature. Patients who garden in Queensland and New South Wales should be advised to handle these insects with care, by wearing protective eyewear and gloves when handling citrus trees or when removing them from their gardens, to minimize their risk of corneal damage if sprayed.

Requirements for essential micronutrients during caloric restriction and fasting.

Caloric restriction (CR) or energy restriction, when carefully designed, monitored, and implemented in self-motivated and compliant individuals, proves to be a viable non-pharmacologic strategy for human weight control and obesity management. Beyond its role in weight management, CR has the potential to impede responses involved not only in the pathogenesis of various diseases but also in the aging process in adults, thereby being proposed to promote a healthier and longer life. The core objective of implementing caloric restriction is to establish a balance between energy intake and expenditure, typically involving a reduction in intake and an increase in expenditure-a negative balance at least initially. It may transition toward and maintain a more desired equilibrium over time. However, it is essential to note that CR may lead to a proportional reduction in micronutrient intake unless corresponding supplementation is provided. Historical human case reports on CR have consistently maintained adequate intakes (AI) or recommended dietary allowances (RDA) for essential micronutrients, including vitamins and minerals. Similarly, longevity studies involving non-human primates have upheld micronutrient consumption levels comparable to control groups or baseline measures. Recent randomized controlled trials (RCTs) have also endorsed daily supplementation of multivitamins and minerals to meet micronutrient needs. However, aside from these human case reports, limited human trials, and primate experiments, there remains a notable gap in human research specifically addressing precise micronutrient requirements during CR. While adhering to AI or RDA for minerals and vitamins appears sensible in the current practice, it's important to recognize that these guidelines are formulated for generally healthy populations under standard circumstances. The adequacy of these guidelines in the setting of prolonged and profound negative energy balance remains unclear. From perspectives of evidence-based medicine and precision nutrition, this field necessitates comprehensive exploration to uncover the intricacies of absorption, utilization, and metabolism and the requirement of each hydrophilic and lipophilic vitamin and mineral during these special periods. Such investigations are crucial to determine whether existing daily dietary recommendations for micronutrients are quantitatively inadequate, excessive, or appropriate when energy balance remains negative over extended durations.

Pulmonary Artery Wedge Pressure Can Underestimate Direct Pulmonary Vein Pressure in Pediatric Pulmonary Vein Stenosis

BackgroundPulmonary artery wedge pressure (PAWP) can underestimate directly measured pulmonary vein pressure (PVP) as demonstrated in animal studies and human case reports. This concept has not been validated in a larger cohort of pediatric patients with pulmonary vein stenosis (PVS). MethodsPediatric patients who underwent cardiac catheterization for PVS at a single center from January 1, 2018, to March 31, 2023, were retrospectively reviewed. Mismatch between the PAWP and directly measured PVP or LA pressure was defined as >3 mm Hg. Preintervention angiography was reviewed and percent stenosis calculated. ResultsTwenty-six patients met inclusion criteria; 51 lower pulmonary veins (34 left, 17 right) from 42 catheterizations were evaluated. Significant PVS (≥30% stenosis) was seen in 38/51 (75%) veins, and 9/51 (18%) veins had no angiographic narrowing (0% stenosis). PAWP-PVP mismatch occurred in 37/51 (73%) veins with a median difference of 8 mm Hg (IQR, 6-12). Of these, PAWP was equal to LA pressure in 26 instances, all of which had significant PVS (median % stenosis 54 [IQR, 45-60]). Six of the cases with PAWP-PVP mismatch, PVS (range, 41%-70% stenosis), and no PAWP-LA mismatch reported both a proximal and distal segmental PAWP. In all 6 instances, there was no distal PAWP-PVP mismatch (median difference 1 mm Hg [range, 0-3]). ConclusionsIn this single-center study of pediatric patients with PVS, PAWP significantly underestimated directly measured PVP in lower pulmonary veins. Balloon wedge or end hole catheter position in a distal lobar segment may more accurately estimate the PVP.

The rise, fall, and resurgence of phage therapy for urinary tract infection

ABSTRACT In the face of rising antimicrobial resistance, bacteriophage therapy, also known as phage therapy, is seeing a resurgence as a potential treatment for bacterial infections including urinary tract infection (UTI). Primarily caused by uropathogenic Escherichia coli , the 400 million UTI cases annually are major global healthcare burdens and a primary cause of antibiotic prescriptions in the outpatient setting. Phage therapy has several potential advantages over antibiotics including the ability to disrupt bacterial biofilms and synergize with antimicrobial treatments with minimal side effects or impacts on the microbiota. Phage therapy for UTI treatment has shown generally favorable results in recent animal models and human case reports. Ongoing clinical trials seek to understand the efficacy of phage therapy in individuals with asymptomatic bacteriuria and uncomplicated cystitis. A possible challenge for phage therapy is the development of phage resistance in bacteria during treatment. While resistance frequently develops in vitro and in vivo , resistance can come with negative consequences for the bacteria, leaving them susceptible to antibiotics and other environmental conditions and reducing their overall virulence. “Steering” bacteria toward phage resistance outcomes that leave them less fit or virulent is especially useful in the context of UTI where poorly adherent or slow-growing bacteria are likely to be flushed from the system. In this article, we describe the history of phage therapy in treating UTI and its current resurgence, the state of its clinical use, and an outlook on how well-designed phage therapy could be used to “steer” bacteria toward less virulent and antimicrobial-susceptible states.

Clinical Use of a Mineral-Organic Resorbable Bone Adhesive: A First Human Case Report with a 3-Year Follow-up.

The ability for clinicians to adequately obtain primary stability in host bone is critical to the success of dental implants. Numerous conditions require dentists to perform multistage approaches to rebuild deficient bone volume prior to surgically placing implants. In many instances, implant placement cannot be achieved due to a lack of primary implant stability. Recently, a novel mineral-organic resorbable bone adhesive (MORBA) has demonstrated promising results in animal studies. MORBA is a synthetic, injectable, self-setting, load-bearing adhesive biomaterial that exhibits osteopromotive properties and bonds bone to bone and metal within 10 minutes and can fully resorb in 30 weeks. Its unique novel formulation was developed from biomimetic proteins found in marine animal creatures that possess distinct adhesive properties underwater. Excellent long-term results have shown its potential use for achieving primary stability in immediate implants. The present case report demonstrates the first use of MORBA in a human patient, utilized on a nonrestorable mandibular first molar. MORBA was utilized after placement of a mobile 5.8-mm implant to achieve stabilization. At 3 months postsurgery, both clinical and CBCT evaluations showed maintained implant stability. One year after implant placement, radiographic bone was seen on the buccal surface of the implant with continued long-term stabilization. This case report extends to 3 years whereby the use of MORBA, in an initially unstable situation, demonstrated an excellent long-term follow-up. MORBA provided immediate implant stability with resorbable characteristics, leading to successful long-term clinical outcomes up to 3 years. This innovative biomaterial offers a more efficient solution to a critical problem in implant dentistry, allowing optimal primary stability during immediate implant placement, thus reducing treatment times and costs.

GATA1 in Normal and Pathologic Megakaryopoiesis and Platelet Development.

GATA1 is a highly conserved hematopoietic transcription factor (TF), essential for normal erythropoiesis and megakaryopoiesis, that encodes a full-length, predominant isoform and an amino (N)terminus-truncated isoform GATA1s. It is consistently expressed throughout megakaryocyte development and interacts with its target genes either independently or in association with binding partners such as FOG1(friend of GATA1). While the N-terminus and zinc finger have classically been demonstrated to be necessary for the normal regulation of platelet-specific genes, murine models, cell-line studies, and human case reports indicate that the carboxy-terminal activation domain and zinc finger also play key roles in precisely controlling megakaryocyte growth, proliferation, and maturation. Murine models have shown that disruptions to GATA1 increase the proliferation of immature megakaryocytes with abnormal architecture and impaired terminal differentiation into platelets. In humans, germline GATA1 mutations result in variable cytopenias, including macrothrombocytopenia with abnormal platelet aggregation and excessive bleeding tendencies, while acquired GATA1s mutations in individuals with trisomy 21 (T21) result in transient abnormal myelopoiesis (TAM) and myeloid leukemia of Down syndrome (ML-DS) arising from a megakaryocyte-erythroid progenitor(MEP). Taken together, GATA1 plays a key role in regulating megakaryocyte differentiation, maturation, and proliferative capacity. As sequencing and proteomic technologies expand, additional GATA1 mutations and regulatory mechanisms contributing to human diseases of megakaryocytes and platelets are likely to be revealed.

Warfarin and bisphosphontes interaction in patients undergoing total knee arthroplasty

BackgroundPatients undergoing knee arthroplasty (TKA) surgery need anticoagulant therapy, mainly warfarin for prevention of venous thromboembolism (VTE). Warfarin is mainly eliminated by renal glomerular filtration where 92 % of warfarin is excreted in urine. Warfarin overdose may lead to significant bleeding and warfarin underdosing may cause VTE and other complications. Thus, international normalized ratio (INR) monitoring is crucial in TKA patients taking warfarin. Great interest has been expressed in bisphosphonate to reduce periprosthetic osteoporosis in patients undergoing total joint arthroplasty. Many human case reports and cohort studies proved bisphosphonates induced impaired renal function. ObjectivesThe main goal of the current study is to examine the pharmacodynamin effect of bisphosphonates on warfarin excretion and clinical effects in patients undergoing TKA surgery. MethodsFifty patients undergoing TKA were recruited in the current study. Twenty five patients were given warfarin and twenty five patients were given warfarin and bisphosphonates starting three days after surgery. INR, major bleeding events and minor bleeding events were followed up in all recruited patients for one month after surgery. Resultswarfarin plus zoledronic acid group had significantly higher percent of post INR greater than 4 (p = 0.022) and significantly higher percent of minor bleeding events (p = 0.041) than warfarin only group. ConclusionConcomitant administration of bisphosphonates may increase warfarin bleeding adverse effects in elderly patient undergoing TKA.

Experimental Evidence of the Diarrheal Activity of Sarcocystis sp. in Sika Deer (Cervus nippon).

Recently, the wild deer population has been increasing in Japan, causing serious feeding-related damage to the agricultural and forestry industries. In conjunction with the government's promotion of hunting for population control, the effective utilization of resources and promotion of the game meat industry as a sixth sector of industrialization are desired by local governments. However, several cases in which patients showed intestinal symptoms such as diarrhea due to the consumption of sika deer meat infected with protozoan Sarcocystis spp. have been reported, and the pathogenic microorganisms found in wild deer should be investigated. In this study, Sarcocystis sp. parasitized Kyushu sika deer (Cervus nippon nippon) in Nagasaki Prefecture, Japan, was examined for its enterotoxicity. A phylogenetic analysis based on the sequence of the 18S rRNA gene and cox1 showed that the species was highly homologous to Sarcocystis japonica and/or Sarcocystis sp. HM050622. We attempted to confirm the diarrhea-evoking toxicity of Sarcocystis sp. in sika deer meat, which has been previously reported in human case reports. A mouse ileal loop assay showed that Sarcocystis sp. in sika deer meat induced significant fluid accumulation in the loop at doses of ∼5 × 106 bradyzoites. Western blotting showed that these Sarcocystis parasites possess actin-depolymerizing factor, a diarrhea-evoking factor, similar to Sarcocystis fayeri, which exists in horsemeat. However, the pathogenic conditions of the ileal loop were different from those of similar experiments with S. fayeri. This study suggests that S. japonica parasitizing C. n. nippon may cause diarrhea via a different mechanism from that of S. fayeri.

Transvenous Radiofrequency Catheter Ablation for an Aldosterone-Producing Tumor of the Left Adrenal Gland: A First in Human Case Report

PurposeTo describe a novel technique of transvenous radiofrequency catheter ablation of an aldosterone-producing adenoma (APA) of the left adrenal gland using the GOS System (Japan Lifeline, Tokyo, Japan). Using the GOS system, a flexible radiofrequency tip catheter can be inserted into the adrenal central and tributary veins, the drainers for functional tumors.Materials and methodsAn APA at the left adrenal gland, which was diagnosed by segmental adrenal venous sampling following administration of 0.25 mg cosyntropin, was ablated using the GOS catheter inserted into adrenal tributary veins via a right femoral vein 7-Fr sheath. The effect of radiofrequency ablation on APA was assessed using the international consensus on surgical outcomes for unilateral primary aldosteronism (PA).ResultsNo device-related complications were observed. The patient was deeply sedated under blood pressure and heart rate control with continuous administration of β-blockers. Then, the tumor and surrounding adrenal gland were cauterized at 7000 J two times each in sequence. The output time was 7−11 min for each ablation and 80 min in total. For blood pressure and pulse rate control, esmolol hydrochloride and phentolamine mesylate were used. The contrast enhancement of APA disappeared on dynamic CT immediately after the procedure. PA was biochemically cured until 12 months after the procedure.ConclusionUsing the radiofrequency device with the GOS catheter and system is a method for cauterizing adrenal tumors from blood vessels. This approach resulted in a marked reduction in aldosterone concentrations and a complete biochemical cure of PA over the observation period.Graphical

Metastatic sarcomas of the oral cavity: A systematic review

Oral metastatic sarcomas (OMSs) occur only occasionally, and information about their characteristics is based on the restricted number of cases reported in the literature. This study aims to systematically review the English literature to recognize the clinicopathologic characteristics of OMSs. An electronic search was performed in PubMed Central and Scopus databases. The search included all the published articles (human case reports and case series) up till April 2023, with no time restrictions. OMSs were slightly more prevalent in males in their fifth to seventh decades of life. However, a high percentage of OMSs has been reported in the second decade of life. Lower extremities, breasts and uterus are the most common primary origin of metastatic sarcoma. Gingiva and mandible were common locations in the oral cavity for metastatic deposits. Generally, they demonstrated widespread affliction. The mean time interval between primary tumor detection and diagnosis of the oral metastasis was about 33.54 ± 36.19 months. Death was reported in 83 patients (67.48 %) with a mean survival rate of 7.98 ± 10.30 months. The most common microscopic tumor types were leiomyosarcoma (n = 21, 17 %), followed by angiosarcoma (n = 20, 16.26 %) and osteosarcoma (n = 18, 14.63 %). In conclusion, while oral metastases of sarcomas are not common, those should be considered in the differential diagnosis of the oral lesions. Although OMSs show a high occurrence in the 7th decade of the life, the average age of patients with oral involvement is lower than the overall metastatic lesions. OMSs may present as widespread disease with poor prognosis.

Volumetric graft changes after liver transplantation: evidence of adaptation to recipient body size.

It is believed that whole liver grafts adjust their size to fit the body size of the recipient after transplantation, despite a lack of evidence. The aim of this study was to test this hypothesis. This was a retrospective cohort study of 113 liver transplantations performed at Karolinska University Hospital. The cohort was divided based on graft volume-to-standard liver volume ratio (GV/SLV) into quartiles of small, mid, and large grafts. Serial volumetric assessment was performed on the day of transplantation and at posttransplant check-ups early (<2 mo) and late (9-13 mo) after transplantation using computed tomography (CT) volumetry. Change in GV/SLV ratio over time was analyzed with ANOVA repeated measures. A multiple regression model was used to investigate the influence of intraoperative blood flow, recipient body size, age, and relative sickness on graft volume changes. Between the three time points, mean GV/SLV ratio adapted to 0.55-0.94-1.00 in small grafts (n = 29, P < 0.001); 0.87-1.18-1.13 in midgrafts (n = 56, P < 0.001); 1.11-1.51-1.18 in large grafts (n = 28, P < 0.001). Regression analysis showed a positive correlation between posttransplant graft growth and portal flow (β = 1.18, P = 0.005), arterial flow (β = 0.17, P = 0.001), and recipient body surface area (β = 59.85, P < 0.001). A negative correlation was observed for graft weight-to-recipient weight ratio (GRWR; β = -33.12, P < 0.001). Grafts with initial GV/SLV-ratio < 0.6 adapt toward the ideal volume for recipient body size 1 year after transplantation. The disparity between graft size relative to recipient body size, and the portal and arterial perfusion, influence volumetric graft changes.NEW & NOTEWORTHY This is the first and largest human study to verify the hypothesis that whole liver grafts adjust their size to match recipient body size 1 year after transplantation-a phenomenon that has previously only been observed in experimental animal studies and human case reports. The direction of volumetric changes is driven by the disparity between graft size relative to recipient body surface area and weight, as well as the intraoperative portal- and arterial graft perfusion.

Abdominal aortic junctional tourniquet (AAJT-S): a systematic review of utility in military practice

IntroductionHaemorrhage is the leading cause of potentially survivable death on the battlefield. Despite overall improvement in battlefield mortality, there has been no improvement in survival following non-compressible torso haemorrhage (NCTH)....

Spaceflight Recovery Considerations for Acute Inhalational Exposure to Hydrazines.

INTRODUCTION: Inhalation of hydrazine or hydrazine-derivative (for example, monomethylhydrazine) vapors during spaceflight operations remains a risk to crew and ground support personnel. Here we sought to provide an evidence-based approach to inform acute clinical treatment guidelines for inhalational exposures during a noncatastrophic contingency spaceflight recovery scenario.METHODS: A review of published literature was conducted concerning hydrazine/hydrazine-derivative exposure and clinical sequelae. Priority was given to studies that described inhalation though studies of alternative routes of exposure were additionally reviewed. Where possible, human clinical presentations were prioritized over animal studies.RESULTS: Rare human case reports of inhalational exposure and multiple animal studies provide evidence of varied clinical sequelae, including mucosal irritation, respiratory concerns, neurotoxicity, hepatotoxicity, hemotoxicity (including Heinz body development and methemoglobinemia), and longitudinal risks. In an acute timeframe (minutes to hours), clinical sequelae are likely to be limited to mucosal and respiratory risk; neurological, hepatotoxic, and hemotoxic sequelae are unlikely without recurrent, longitudinal, or noninhalational exposure.CONCLUSIONS: Acute clinical management should focus on likely clinical concerns as supported by existing data; recovery medical personnel should be prepared to manage mucosal irritation and respiratory concerns, including the potential need for advanced airway management. There is little evidence supporting the need for acute interventions for neurotoxicity and there is no evidence that acute hemotoxic sequelae would drive the need for on-scene management of methemoglobinemia, Heinz body development, or hemolytic anemia. Training that overemphasizes neurotoxic or hemotoxic sequelae or specific treatments for such conditions potentially raises the risk for inappropriate treatment or operational fixation.Hanshaw BC, Ryder VE, Johansen BD, Pattarini JM, Nguyen HN, Nowadly CD, Blue RS. Spaceflight recovery considerations for acute inhalational exposure to hydrazines. Aerosp Med Hum Perform. 2023; 94(7):532-543.

A narrative review of prehospital hemorrhagic shock treatment with non-blood product medications.

Hemorrhagic shock remains a leading cause of death in both military and civilian trauma casualties. While standard of care involves blood product administration, maintaining normothermia, and restoring hemostatic function, alternative strategies to treat severe hemorrhage at or near the point of injury are needed. We reviewed adjunct solutions for managing severe hemorrhage in the prehospital environment. We performed a literature review by searching PubMed with a combination of several keywords. Additional pertinent studies were identified by crossreferencing primary articles. Clinical experience of each author was also considered. We identified several promising antishock therapies that can be utilized in the prehospital setting: ethinyl estradiol sulfate (EES), polyethylene glycol 20,000 (PEG20K), C1 esterase inhibitors (e.g. Berinert, Cinryze), cyclosporin A, niacin, bortezomib, rosiglitazone, icatibant, diazoxide, and valproic acid (VPA). Several studies show promising adjunct treatment options in the management of severe prehospital hemorrhage. While some are rarely used, many others are readily available and commonly utilized for other indications. This suggests the potential for future use in resourcelimited settings. Human studies and case reports supporting their use are currently lacking.

Intravenous topiramate for seizure emergencies – First in human case report

Topiramate (TPM) is widely used in focal and generalized epilepsies. It is commercially available as tablets and sprinkles capsules for oral treatment. Previous studies comparing intravenous (IV) to oral TPM in healthy adults showed more rapid pharmacodynamic effects in cases of IV administration. Despite promising findings, no clinical application in humans followed. We present a case of a pregnant woman with idiopathic generalized epilepsy who experienced a generalized tonic-clonic seizure in the third trimenon due to low TPM levels attributed to pregnancy followed by repeated prolonged absences. We applied a new meglumine-based solution (1%) of TPM (10 mg/ml) in two IV infusions of 200 mg each under EEG monitoring over a total duration of 1 hour. The infusion was well tolerated and led to a rapid increase in plasma TPM levels. A clinical as well as electroencephalographic improvement was documented within the first hours. To the best available knowledge, this is the first reported case where IV TPM was used therapeutically for seizure treatment in humans. It is also the first time that the new meglumine-based solution was used in a human with epilepsy. The advantages of IV route delivery and the solution’s quick preparation, high tolerability, and low toxicity make it ideal for use in many clinical settings and high-care patients. IV TPM seems to be a reasonable adjunctive option for adults with seizures, previously stabilized on oral TPM, who need rapid plasma concentration boosting. Although our experience was successful in using injectable TPM in seizure emergencies, randomized controlled clinical trials are required to make recommendations for the use of IV TPM on patients with epilepsy.This paper was presented at the 8th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures held in September 2022 in Salzburg, Austria.

Lipid Emulsion Treatment for Drug Toxicity in Pediatric Patients

Medication mistakes continue to be one of the most serious issues in hospitals. Such mistakes can occur during the prescription, distribution, or administration of medications. Lipid emulsions are commonly utilized in whole or partial parenteral feeding initially, Following convincing results from animal models and effective case reports in humans, the use of intravenous lipid emulsions (ILEs) as an antidote in local anesthetic systemic toxicity has acquired considerable acceptance. Although intravenous lipid emulsion (ILE) was initially employed to treat life-threatening local anesthetic (LA) toxicity, its application has broadened to cover non-LA poisoning and less severe symptoms of toxicity. However, in recent years, the function of lipid emulsions in the treatment of lipophilic chemical toxicity and overdose has been established. In addition to typical poisoning treatment, lipid emulsion therapy was employed. The observed sequence of events provides substantial support for the importance of ILE treatment in the effective management of both instances. However, further study is needed in this area to provide definite guidelines for the use of intravenous lipid emulsions in pediatric lipophilic agent poisoning. The body of data supporting the use of ILEs in acute drug intoxication is growing. The current data supports the use of ILEs only when there is an imminent threat to life from local anesthetic systemic toxicity or lipophilic cardio-toxin poisoning. Lipid emulsion therapy is a potential and less expensive alternative in cases of acute lipophilic poisoning where a specific antidote is unavailable.