Rapid Normalization Research Articles

Refractory Hyperlactatemia After a Septic Shock in a Patient With Carnitine Deficiency: A Case Report

A 56-year-old woman with septic shock presented with persistent hyperlactatemia, despite an adequate clinical response to treatment. Carnitine deficiency was suspected, as the patient was malnourished and chronically taking valproic acid. No other plausible cause of hyperlactatemia was found. Carnitine supplementation resulted in rapid normalization of lactatemia.

Оцінка показників коагулограми у пацієнтів з тромбозом системи нижньої порожнистої вени

Мета. Оцінити зміни показників коагулограми у пацієнтів з тромбозом глибоких вен (ГВ) системи нижньої порожнистої вени (НПВ) залежно від виду лікування.
 Матеріали і методи. Проведена кількісна оцінка показників коагулограми у 615 пацієнтів із тромбозом у системі НПВ. Залежно від методу лікування хворі розподілені на дві групи: 1-ша – 380 (61,8%) хворих, яким провели хірургічне лікування з наступним призначенням антикоагулянтної терапії; 2-га – 235 (38,2%) хворих, яким призначали лише антикоагулянтну терапію.
 Результати. Оцінка більшості показників коагулограми показала більш виражену гіпокоагуляцію у пацієнтів 1-ї групи порівняно з 2-ю групою: рівень D-димеру був нижче на 14,1%, середня концентрація тромбокриту (СКТ) - на 7,8%, протромбіновий індекс (ПІ) - на 7,1%, міжнародне нормалізоване співвідношення (МНС) - на 3,8%, рівень гематокриту - на 2,4%, кількість тромбоцитів - на 1,9%. У пацієнтів 1-ї групи спостерігали більш виражене подовження активованого часткового тромбопластинового часу (АЧТЧ), активованого часу рекальцифікації (АЧР) та протромбінового часу (ПЧ) порівняно з пацієнтами 2-ї групи: на 37,9, 10,6 та 4,8% відповідно. Водночас рівень фібриногену у 1-й групі був на 9,1% вище порівняно з 2-ю групою.
 Висновки. Гіпокоагуляційні зміни гемостазу у пацієнтів, яким застосували хірургічне лікування тромбозу ГВ системи НПВ, порівняно з пацієнтами, яким призначали лише антикоагулянтну терапію, дають підстави припустити, що механічне видалення тромботичних мас сприяє більш швидкій нормалізації показників гемостазу.

Abstract A05: Investigating mechanisms of obesity-mediated pancreatic cancer progression

Abstract Genetically engineered mouse models (GEMMs) that faithfully recapitulate the genetics and histology of human tumors are an underutilized tool to understand how modifiable risk factors influence tumor development. Prospective cohort studies have shown that obesity is associated with an increased risk of developing pancreatic cancer, more advanced disease at diagnosis, and worse survival, though the precise mechanisms behind which obesity contributes to cancer progression remain elusive. We crossed mice harboring loss-of-function mutations in the leptin gene (ob/ob) with Pdx1-Cre; LSL-KrasG12D (KC) mice predisposed to initiate pancreatic cancers. KC; ob/ob mice are obese and exhibit markedly shortened survival (~4 months vs. ~1 year), increased primary tumor burden, and enhanced progression to adenocarcinoma compared to nonobese KC mice. Interestingly, early correction of leptin deficiency using an adeno-associated virus (AAV)-based approach induces rapid normalization of body weight and hyperglycemia and completely prevents the emergence of enhanced tumor burden. In contrast, late leptin restoration following tumor progression does not impact survival. These data suggest a causal and reversible role for obesity in early pancreatic cancer progression. Furthermore, by evaluating the degree by which alternative interventions phenocopy the effects of leptin restoration, we have developed a model to rapidly interrogate mechanisms of obesity-mediated tumor progression. As a proof of principle, we have tested the ability of immunomodulatory (aspirin) and antidiabetic (metformin) agents, observed to impact pancreatic cancer risk and survival in human cohorts, to intercept cancer progression in this model. Finally, combined molecular and biochemical analyses of tumors reveal increased immune cell activation and fibrosis in KC; ob/ob mice compared to nonobese KC and KC; p53 mutant mice and provide specific molecular targets to evaluate for pancreatic cancer therapy and prevention. Citation Format: Mandar Deepak Muzumdar, Kimberly Judith Dorans, Katherine Minjee Chung, Arjun Bhutkar, Charles Fuchs, Tyler Jacks. Investigating mechanisms of obesity-mediated pancreatic cancer progression [abstract]. In: Proceedings of the AACR Special Conference: Advances in Modeling Cancer in Mice: Technology, Biology, and Beyond; 2017 Sep 24-27; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(10 Suppl):Abstract nr A05.

Hepcidin regulation in a mouse model of acute hypoxia.

During hypoxia, hepcidin expression is inhibited to allow iron mobilization to sustain erythropoietic expansion. We analyzed molecular mechanisms underlying hypoxia-induced hepcidin inhibition in an in vivo model of acute hypoxia. Mice were kept under normal or hypoxic conditions for 6hours and 15hours and treated with α-PDGF-BB antibody or PDGF-BB receptor inhibitor. Blood, liver, spleen, and bone marrow were collected to extract RNA and protein or to quantify EPO and PDGF-BB. mRNA and protein levels were assessed by RT-PCR and Western blot. Hepcidin was strongly inhibited at 15hours, and this downregulation followed erythropoiesis activation and upregulation of several growth factors. PDGF-BB, erythroferrone, GDF15, and TWSG1 were upregulated by hypoxia in the bone marrow, but not in spleen or liver. Inactivation of PDGF-BB or its receptor suppressed the hypoxia-induced hepcidin inhibition. Spleen and liver are not involved in the early stages of hypoxia-induced hepcidin downregulation. Our data support the role of PDGF-BB and probably also of erythroferrone in the recruitment of iron for erythropoiesis in the hypoxia setting. The rapid normalization of all the erythroid factors against persistent hepcidin suppression suggests that other signals are involved that should be clarified in future studies.

A comparative description of dynamics of metabolic response indexes in the phases of burn disease course depending on terms of the onset of surgical intervention.

A question of possibilities of influence on decline of progressing systemic response on the burn trauma remains open, despite actuality and active study of this problem. The aim of this work was carrying out a comparative description of dynamics of metabolic response indexes in the phases of burn disease (BD) course depending on terms of the beginning of the surgical intervention. Рatients with a thermal trauma were inspected and analyzed in this work. All the patients were estimated for the index of the thermal defeat severity, the percentage of the area of deep burn, a general area of burn, the age of a patient and the presence of respiration system burn. According to these, all the patients were divided into separate groups of research. The 1st group included 46 injured with the index of thermal defeat severity (TDS) from 61 to 90 units. The 2 group included 29 patients with the TDS index over 91 units. According to the terms of surgical intervention, patients of these groups were divided into sub-groups: 1.1 and 2.1, where the first surgical intervention was conducted five days before burn disease; 1.2 and 2.2, where the first surgical intervention was conducted five days after of burn disease. The level of cortisol and glycaemia of blood serum of injured people on different stages of inspection were taken into consideration. The diagnostically-curative program was conducted according to the clinical protocol of medical care to injured with thermal trauma. Estimating the dynamics of cortisol level, there was a considerable increase of it over the first twenty-four hours in both groups, which preserved during an acute period of burn disease. In the patients of the sub-group 2.1, with the TDS index over 91 units, who underwent early surgical tactics, the further activating of a sympathic adrenal system on the 7th day after the burn (an increase in cortisol by 82% compared with the previous indicator) was noted. From the first twenty-four hours after the burn, injured people suffered from a stress-induced hyperglycaemia which developed in all research groups, the latter did not depend on the severity of the burn trauma and did not correlate with the cortisol level of blood serum. With the early surgical treatment of burns, a more rapid normalization of blood glucose level in patients of 1.1 and 2.1 sub-groups on the 5th and 7th day of burn disease accordingly occurred.

CORRECTION OF DISTURBED NEUROIMMUNE INTERACTIONS IN EXPERIMENTAL TRAUMATIC BRAIN INJURY BY MEANS OF RECOMBINANT INTERLEUKIN 2

Traumatic brain injury (TBI) commonly proceeds as a severe disease with high morbidity that can lead to neurological disorders in some of these patients. TBI is associated by multidirectional abnormalities of immune system, which affect quantity and functions of T-, B-, and NK-lymphocytes leading to infectious complications or autosensibilization. Restoration of the disturbances in neuroimmune interactions after TBI may be achieved by means of immunomodulators that have neuroprotective properties and may potentially initiate regenerative CNS activity. IL-2 is a cytokine that possesses neurooperative and neuroprotective properties. In immune system, IL-2 is produced by T-cells in response to antigen stimuli; in CNS, by brain cells. Lack of IL-2 production by both T-lymphocytes and brain cells increases a possibility of autoimmune and inflammatory pathologies. The objective of present study was to evaluate possible effects of human recombinant IL-2 (rIL-2, Roncoleukin®, Biothech Ltd., Russia) upon state and correction of immune and neuro-endocrine TBI consequences. The study was performed in adult Wistar rats. Mechanical TBI was produced by the dropping load model. 72 hours after inflicting the TBI, r-IL-2, at dose 30 mg/kg was injected once a day for three times. The animals from control group received 0.15M NaCl solution over the same period. The results have shown that, within first hours and days after TBI, corticosterone levels showed a sharp increase, whereas testosterone concentrations were decreased.In parallel, an increase in cytotoxic and proliferative activity of splenocytes was revealed, as well as increased number of splenocytes at their late apoptotic stage. Three daily injections of rIL-2 resulted into a significant increase in corticosterone and testosterone levels in injured animals on the day 7 after TBI. The animals treated with rIL-2 have exhibited more rapid normalization of cytotoxic and proliferative activity of splenocytes and return to normal ratio of proliferating splenocytes vs. apoptotic cells. Therefore, usage of rIL-2 may correct neuro-endocrine and immune interaction disturbances after TBI and decrease risk of chronic neurological disorders in TBI patients.

4:03 PM Abstract No. 118 Protein-losing enteropathy following thoracic duct ligation: diagnosis and treatment

Protein-losing enteropathy (PLE) is a condition characterized by severe loss of proteins in the intestinal tract. This report describes a series of pediatric patients who developed PLE following thoracic duct (TD) ligation. A retrospective review of 3 consecutive patients (M/F = 2/1; mean age 5.5 years) who developed PLE following TD ligation was performed. Lymphatic imaging included Dynamic Contrast Enhanced MR lymphangiogram (DCRML) and/or intranodal lymphangiogram (IL). Two patients (P1, P2) developed PLE following TD ligation for post-cardiac surgery chylothorax and the third patient (P3) following TD ligation for idiopathic chylothorax. The post-ligation course was complicated by anasarca, severe hypoalbuminemia (mean 1.4 mg/dL), and electrolyte imbalances in all subjects. P1 and P3 had elevated stool alpha1-antitrypsin (A1A) (mean 324 mg/dL; reference ≤54 mg/dL). A1A for patient P2 was not documented. On DCRML, all patients had an occlusion of the TD and retrograde lymphatic flow through the intestinal lymphatic duct with leakage of the contrast into the lumen of the intestines. For P1 and P2, conservative treatment with oral steroids, sildenafil, octreotide, heparin, and diet modification was unsuccessful. In these patients, IL was performed followed by percutaneous access of the intestinal lymphatic ducts and embolization with n-BCA glue resulting in rapid normalization of albumin and electrolyte levels and symptomatic improvement. In P3, treatment with low fat diet and supplementation similarly resulted in drastic improvement. On follow-up (mean 2.6 months), P1 and P3 remained asymptomatic with normal laboratory values while P2 developed recurrent PLE with lymphatic leak into the intestines 8 months after embolization that is currently being managed medically. Our study demonstrated the unusual development of the PLE in patients following TD ligation due to development of the retrograde lymphatic flow into the intestinal lymphatic ducts. Conservative treatment should be the initial approach. However, if this is unsuccessful, lymphatic embolization should be considered. Further long-term follow-up is needed to determine the durability of this treatment.

Treatment of congenital hypothyroidism in a newborn with malabsorption after subtotal ileum resection.

SummaryCongenital hypothyroidism requires prompt treatment to prevent adverse health outcomes. Poor intestinal levothyroxine absorption can complicate management. We present a case of a term female newborn with necrotizing enterocolitis (NEC) requiring subtotal ileum resection. Congenital hypothyroidism was diagnosed by newborn screening. Treatment was complicated by intestinal malabsorption of levothyroxine. Intravenous levothyroxine substitution restored euthyroidism and supraphysiologic PO doses subsequently maintained a euthyroid state. After several months, the required levothyroxine dose was weaned down to typical recommended dosing. In conclusion, small bowel resection secondary to NEC may lead to malabsorption of oral levothyroxine. An intravenous levothyroxine dose of approximately 50% typical PO dosing is effective in providing rapid normalization of free T4 and TSH. High PO doses may be required to maintain euthyroidism. Close thyroid function monitoring and immediate therapy adjustment are essential as the individual absorption may vary widely. Normal absorption levels may be regained due to adaption of the neonatal intestines.Learning points:In neonates with malabsorption after ileum resection intravenous levothyroxine replacement should be used to provide normalization of free T4 and TSH.Very high doses of up to 500% usual oral levothyroxine may be required to maintain euthyroidism. The estimated degree of malabsorption can be used to determine the initial dose.Close thyroid function monitoring and immediate therapy adjustment are essential as the absorption and intestinal adaption may vary widely.

‘Now She’s Just an Ordinary Baby’: The Birth of IVF in the British Press

The birth of Louise Brown, the first baby born through in vitro fertilisation (IVF), in England in 1978 attracted worldwide media attention. This article examines how the contemporary British news media framed this momentous event. Drawing on the example of the Daily Mail’s coverage, it focuses on the way in which the British press depicted Louise’s parents’ emotions, marital relationship and social class in a context of political and economic crisis and resurgent social conservatism. The British press framed the Browns as ordinary and respectable, noting their work ethic, family orientation and moral values. The article argues that the human-interest angle that the press used to represent this story created a dominant narrative in which IVF was simply a means of helping married heterosexual couples have babies and that this established a frame for subsequent depictions of IVF, as well as contributing to its rapid normalisation.

СОЧЕТАННАЯ ТРАНСПЛАНТАЦИЯ ГЕПАТОЦИТОВ С МЕЗЕНХИМАЛЬНЫМИ СТВОЛОВЫМИ КЛЕТКАМИ КОСТНОГО МОЗГА НА КЛЕТОЧНЫХ НОСИТЕЛЯХ ИЗ ПОРИСТО-ПРОНИЦАЕМОГО НИКЕЛИДА ТИТАНА

The aim of the research was to study of the therapeutic efficacy of combined transplantation of liver cells and mesenchymal stem cells of bone marrow (MSC) on TiNi-based alloy scaffolds of rats with chronic hepatitis. Materials and methods: Three groups of experiments were carried out on Wistar rats and intact rats (control) - I group; in the II group - chronic hepatitis; III group - cell-engineering designs with liver cells; in the IV group - cell-engineering designs with liver cells and BM MMSC. The activity of recovery processes was evaluated by using biochemical methods in dynamics on 10, 20, 30th days. Results. The optimal ratio of liver cells to MSC (5:1) was previously found in TiNi-based alloy scaffolds after transplantation and through co-cultivation of hepatocytes and MSC at different ratios. It was shown that recovery processes in the group with scaffolds transplanted into damaged livers were much more active if compared with those in the control group with chronic hepatitis. At the same time, in the group with combined transplantation on TiNi-based alloy scaffolds contributed to a more rapid normalization of liver enzyme indices compared with the group with transplantation of some hepatocytes on scaffolds. These data are confirmed by an increase in the life span of animals with combined hepatocytes and MSC transplantation on TiNi-based alloy scaffolds. Conclusions. A higher level and prolonged periods of liver regeneration during the transplantation of TiNi-based alloy scaffolds are due to the creation of biologically appropriate conditions for cells with certain ratio.

Direct-acting Antiviral Agents in Hepatitis C Virus-infected Renal Allograft Recipients: Treatment and Outcome Experience from Single Center.

Hepatitis C virus (HCV) infection in renal allograft recipient is associated with increased morbidity and mortality. At present, only few studies related to treatment and outcomes of HCV-infected renal allograft recipients with DAAs have been published. We aimed the study to assess the efficacy and safety of sofosbuvir-based regimens in HCV-infected renal allograft recipients. We analyzed data of 22 eligible HCV-infected renal allograft recipients (14 genotype-3, 6 genotype-1, one each genotype-2 and 4) who were treated with DAAs at our institute. DAA regimen included sofosbuvir and ribavirin with or without ledipasvir or daclatasvir for 12–24 weeks. Patients were followed up for 24 weeks after completion of treatment. A rapid viral response of 91%, end of therapy response of 100%, and sustained viral response at 12 and 24 weeks of 100% with rapid normalization of liver enzymes were observed. Therapy was well tolerated except for ribavirin-related anemia. A significant decrease in tacrolimus trough levels was observed and most patients required increase in tacrolimus dose during the study. Treatment with newer DAAs is effective and safe for the treatment of HCV-infected renal allograft recipients.

Regulation of thyroid sodium-iodide symporter in different stages of goiter: Possible involvement of reactive oxygen species.

Na+ /I- symporter (NIS) transports iodide into thyrocytes, a fundamental step for thyroid hormone biosynthesis. Our aim was to evaluate NIS regulation in different status of goitrogenesis and its underlying mechanisms. Wistar rats were treated with methimazole (MMI) for 5 and 21days, to achieve different status of goiter. We then evaluated the effect of MMI removal for 1day (R1d), after 5 (R1d-5d) or 21 (R1d-21d) days of MMI treatment. MMI increased thyroid weight, iodide uptake and in vitro TPO activity in a time-dependent way. Although MMI removal evoked a rapid normalization of TPO activity in R1d-5d, it was still high in R1d-21d. On the other hand, iodide uptake was rapidly down-regulated in R1d-21d, but not in R1d-5d, suggesting that the increased TPO activity in R1d-21d led to increased intraglandular organified iodine (I-X), which is known to inhibit iodide uptake. Since TGFβ has been shown to mediate some effects of I-X, we evaluated TGFβ and TGFβ receptor mRNA levels, which were increased in R1d-21d. Moreover, it has been demonstrated that TGFβ stimulates NOX4. Accordingly, our data revealed increased NOX4 expression and H2 O2 generation in R1d-21d. Finally, we evaluated the effect of H2 O2 on NIS function and mRNA levels in PCCL3 thyroid cell line, which were reduced. Thus, the present study suggests that there is a relationship between the size of the goiter and NIS regulation and that the mechanism might involve I-X, TGFβ, NOX4 and increased ROS production.

Study protocol for a phase II dose evaluation randomized controlled trial of cholecalciferol in critically ill children with vitamin D deficiency (VITdAL-PICU study)

BackgroundClinical research has recently demonstrated that vitamin D deficiency (VDD) is highly prevalent in the pediatric intensive care unit (PICU) and associated with worse clinical course. Multiple adult ICU trials have suggested that optimization of vitamin D status through high-dose supplementation may reduce mortality and improve other clinically relevant outcomes; however, there have been no trials of rapid normalization in the PICU setting. The objective of this study is to evaluate the safety and efficacy of an enteral weight-based cholecalciferol loading dose regimen in critically ill children with VDD.Methods/designThe VITdAL-PICU pilot study is designed as a multicenter placebo-controlled phase II dose evaluation pilot randomized controlled trial. We aim to randomize 67 VDD critically ill children using a 2:1 randomization schema to receive loading dose enteral cholecalciferol (10,000 IU/kg, maximum of 400,000 IU) or a placebo solution. Participants, caregivers and outcome assessors will be blinded to allocation. Eligibility criteria include ICU patient, aged 37 weeks to 18 years, expected ICU length of stay more than 48 h, anticipated access to bloodwork at 7 days, and VDD (blood total 25 hydroxyvitamin D < 50 nmol/L). The primary objective is to determine whether the dosing protocol normalizes vitamin D status, defined as a blood total 25(OH)D concentration above 75 nmol/L. Secondary objectives include an examination of the safety of the dosing regimen (e.g. hypercalcemia, hypercalciuria, nephrocalcinosis), measures of vitamin D axis function (e.g. calcitriol levels, immune function), and protocol feasibility (eligibility criteria, protocol deviations, blinding).DiscussionDespite significant observational literature suggesting VDD to be a modifiable risk factor in the PICU setting, there is no robust clinical trial evidence evaluating the benefits of rapid normalization. This phase II clinical trial will evaluate an innovative weight-based dosing regimen intended to rapidly and safely normalize vitamin D levels in critically ill children. Study findings will be used to inform the design of a multicenter phase III trial evaluating the clinical and economic benefits to rapid normalization. Recruitment for this trial was initiated in January 2016 and is expected to continue until November 30, 2017.Trial registrationClinicaltrials.gov NCT02452762

Littoral cell angioma of the spleen revealed by a Kasabach-Merritt syndrome in a 22-month-old child

Introduction: Kasabach-Merrit syndrome (KMS) is characterized by the association of a vascular tumor, thrombocytopenia and potentially life-threatening coagulopathy. Observation: A 22-month-old child was referred to our center for incidental discovery of thrombocytopenia in a context of recurrent throat infections. Clinical examination showed petechial purpura, subicterus, no tumoral syndrome and good overall condition. His biological parameters showed regenerative hemolytic anemia (10.2 g/dL), thrombocytopenia (32 G/L), no schistocytes, moderate fibrinopenia and positive D-dimer test. The results of bone marrow analysis and auto-immune tests were normal. No treatment was undertaken given the absence of diagnosis and complication. The child was regularly followed-up in consultation. Complementary investigations ruled out Wilson’s disease, thrombotic thrombocytopenic purpura and constitutional red blood cell disorders. The main hypothesis remained a thrombotic microangiopathy despite absence of schistocytes on repeated blood tests. Two months later, he was rehospitalized for acute clinical and biological worsening with splenomegaly and severe consumption coagulopathy leading to suspect a myeloproliferative syndrome, finally refuted. Steroids were started due to worsening hemorrhagic symptoms, daily transfusion requirements and increasing splenomegaly. Due to worsening health status and risk of threatening rupture, splenectomy was performed and histopathological analysis revealed a vascular lesion infiltrating the whole spleen, compatible with a littoral cell angioma. The child showed rapid clinical improvement and complete hematological normalization within 48 hours post-splenectomy. Conclusion: Littoral cell angioma is a very rare and benign vascular lesion which may be complicated by a life-threatening KMS. This diagnosis should be suspected in patients presenting with splenomegaly and features of thrombotic microangiopathy.

Prolapso rectal como presentación inhabitual de enfermedad celiaca. A propósito de 2 casos clínicos

Rectal prolapse (RP) is related to an increase of intra-abdominal pressure, pelvic floor disease or anal sphincter. The most common causes of RP are constipation, cystic fibrosis, whooping cough and dysenteric diarrhea. However, celiac disease is not considered among the pathologies re lated to RP. To present a scarcely described association between RP and celiac disease. We presented 2 preschoolers in whom the reason for consultation was RP, whose study was focused on as prolonged diarrhea, due to the antecedent of pasty consistency of stools. The tests showed elevated anti-tissue transglutaminase (anti-tTG) antibody titers, and duodenal biopsies with villous atrophy and increased intraepithelial lymphocytes, consistent with celiac disease. Both had an excellent response to the gluten-free diet, with rapid normalization of depositions, without presenting any episodes of RP after treatment. Both with normal staturo-ponderal development and anti-tTG-negative controls at the annual 5-year follow-up. Although the association between RP and celiac disease has not been described yet, it should be considered in diagnosis and treatment.

Smoldering myocarditis following immune checkpoint blockade

BackgroundSevere myocarditis associated with electrical conduction abnormalities and occasionally heart failure has been well documented following treatment with immune checkpoint blockade with an estimated incidence of less than 1%. However, the incidence, early detection, and management of less severe immune-related myocarditis are unknown since most immunotherapy trials have not included routine cardiac monitoring. Herein, we provide the first description of subclinical or smoldering myocarditis with minimal signs and symptoms following immune checkpoint blockade with a single dose of ipilimumab and nivolumab.Case presentationOur patient was diagnosed with immune checkpoint blockade-induced myocarditis based upon an acute rise in serum cardiac troponin I beginning 2 weeks after the initial dose of ipilimumab/nivolumab consistent with the reported median onset of clinical myocarditis at 17 days, as well as a lack of other causes despite extensive cardiac evaluation. The patient initially presented with intractable nausea with no known gastrointestinal etiology. High dose glucocorticoid therapy led to rapid resolution of nausea and a four-fold decrease in troponin I over 4 days. Serum troponin I spiked again following a steroid taper to 13 times the upper limit of normal with endomyocardial biopsy revealing collagen fibrosis and lymphocytic inflammation predominantly comprised of CD8+ T cells consistent with chronic smoldering myocarditis. Serum anti-striated muscle antibodies were also detected with no evidence of rhabdomyolysis. Serum cardiac troponin I levels as an indicator of ongoing myocyte damage gradually improved with chronic prednisone at 10 mg daily. Late addition of intravenous immunoglobulin was associated with rapid normalization of creatine kinase-myocardial band.ConclusionsThis case demonstrates that subclinical, smoldering myocarditis may occur following immune checkpoint blockade, with evidence of both humoral and cell-mediated immunity responsive to corticosteroid therapy. This experience supports early monitoring for myocarditis with serial electrocardiograms and serum troponin I determinations in large, prospective cohorts of patients receiving combination immune checkpoint blockade as early detection and initiation of immunosuppression may forestall fulminant presentation of this disease and limit myocardial damage.

Whole body perfusion strategy for aortic arch repair under moderate hypothermia.

Aortic arch reconstruction under moderate hypothermia is commonly performed with antegrade cerebral perfusion (ACP) for brain protection; however, hypothermia alone is often solely relied upon for visceral and lower body protection. We investigated whether the addition of simultaneous lower body perfusion to ACP (whole body perfusion - WBP) may ameliorate the metabolic derangements of moderate hypothermic circulatory arrest (MHCA). Between 2008 and 2014, 106 consecutive patients underwent elective or emergent aortic arch surgery with MHCA, with either ACP only (44 patients, 66±12 years, 30% female) or WBP (62 patients, 61±15 years, 31% female). Primary outcomes included 30-day/in-hospital mortality, intensive care unit (ICU) and hospital lengths of stay (LOS) and specific parameters of metabolic recovery. There were no significant differences between the groups in 30-day/in-hospital mortality (ACP: 3 (6.8%), WBP: 2 (3.2%); p=0.65), stroke (ACP: 1 (2.3%), WBP: 1 (1.6%); p=1.0) or renal failure (ACP: 2 (4.5%), WBP: 1 (1.5%); p=0.57). In the WBP group, we identified a significant reduction in lactate level at ICU admission (ACP 5.5 vs. WBP 3.5 mmol/L; p=0.002), time to lactate normalization (p=0.014) and median ICU length-of-stay (ACP 3 vs. WBP 1 days; p=0.049). There was no difference in post-operative creatinine (ACP: 104, WBP: 107 μmol/L; p=0.66). After multivariable regression adjustment, perfusion strategy no longer remained an independent predictor of ICU discharge time (p=0.09), however, cardiopulmonary bypass time (p=0.02), age (p=0.012) and emergent surgery (p=0.02) were. A WBP strategy during aortic arch reconstruction with MHCA may be associated with more rapid normalization of metabolic parameters and reduced ICU length of stay compared to using ACP alone. Further evaluation with a randomized trial is warranted.

Thiamine Deficiency Mimicking Guillain-Barré Syndrome

SESSION TITLE: Critical Care 4 SESSION TYPE: Affiliate Case Report Slide PRESENTED ON: Tuesday, October 31, 2017 at 07:30 AM - 08:30 AM INTRODUCTION: Thiamine (Vitamin B1) is an essential vitamin utilized in a number of cellular functions and metabolic pathways. Thiamine deficiency can be associated with peripheral neuropathy (termed dry beriberi), lactic acidosis and cardiovascular insufficiency (wet beriberi). Shoshin beriberi refers to a variant of this condition characterized by acute onset and rapidly progressive deterioration of cardiovascular function which, if not treated could result in cardiovascular collapse and death. CASE PRESENTATION: A 47 year old Cambodian male with no significant past medical history presented with numbness, tingling and progressive weakness of his lower extremities for a month. He drank alcohol occasionally. He was alert and oriented but had decreased lower extremity strength and decreased patellofemoral reflexes bilaterally. Lab work was significant for hyponatremia, hypokalemia, mild renal failure and an elevated lactic acid of 6.1 mg/dL. He was admitted and given fluids for presumed dehydration but had persistent weakness and lactic acidosis. On the third day of his admission, he developed hypotension requiring vaseopressor support. DISCUSSION: An extensive initial work-up including cultures, HIV, hepatitis panel, urine toxicology screen, RPR and rheumatologic testing was negative. An echocardiogram showed normal left ventricular function and evidence of pulmonary hypertension and mild right ventricular dysfunction. CT of the head, cervical spine, chest, abdomen and pelvis were all unremarkable. Electromyography showed demyelination and a diagnosis of Guillain-Barre Syndrome was considered, despite a lumbar puncture showing normal protein levels in the CSF. The patient was administered IVIG. A thiamine level sent on day 2 of his admission resulted at 7 nmol/L (normal 8 -30) 5 days after it was sent confirming a diagnosis of thiamine deficiency. Aggressive thiamine repletion was started, IVIG was stopped and the patient improved with rapid normalization of his lactic acidosis and blood pressure. He also slowly recovered his motor strength. CONCLUSIONS: Severe thiamine deficiency is rare in developed countries, and is likely vastly under-detected in the absence of standardized testing. As has been previously reported1, this case highlights to physicians caring for critically ill patients the potential for missed diagnoses and poor outcomes in patients with thiamine deficiency. Reference #1: 1. Koike, et al “Rapidly developing weakness mimicking Guillain-Barré syndrome in beriberi neuropathy: two case reports.” Nutrition, 2008 DISCLOSURE: The following authors have nothing to disclose: Anton Edwards, Nader Azab, Gerardo Carino No Product/Research Disclosure Information

Hyperéosinophilie isolée précédant le diagnostic d’une fasciite à éosinophiles (maladie de Shulman)

IntroductionEosinophilic fasciitis or Shulman's disease is characterized, in its typical form, by palpable thickening of the skin and soft tissues, blood hypereosinophilia and fascia lesions. We hereby report a case of eosinophilic fasciitis in which hypereosinophilia preceded for several months the clinical signs of fasciitis. Case reportA 64-year-old woman, with a history of Little's syndrome with motor disability, was admitted in internal medicine for eosinophilia. For almost three months, no origin to the eosinophilia was found. The secondary onset of an edema and pain located on four limbs led to the diagnosis of eosinophilic fasciitis. Muscle magnetic resonance imaging was supportive and the muscle histological analysis confirmed the diagnosis of eosinophilic fasciitis. Treatment with steroids induced a rapid normalization of the eosinophilia and edema. ConclusionIn this case report, eosinophilia was preceding the clinical cutaneous signs that led to the diagnosis of eosinophilic fasciitis. It is likely to believe that myalgias, frequently found in the onset of eosinophilic fasciitis, may have been hidden by the history of infantile encephalopathy. The diagnosis of eosinophilic fasciitis must be kept in mind of physicians in the investigation of an eosinophilia, even though cutaneous signs are lacking.

Successful intravenous thrombolysis for ischemic stroke after reversal of dabigatran anticoagulation with idarucizumab: a case report

BackgroundNon-vitamin K antagonist oral anticoagulants, including dabigatran, are currently widely used for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation. Recently, idarucizumab, a monoclonal antibody fragment for immediate reversal of dabigatran-induced anticoagulation, has been introduced into the market to be used in life-threatening bleeding or urgent surgery, allowing for rapid normalization of clotting parameters. The use of idarucizumab is not yet well established in patients presenting with acute ischemic stroke on dabigatran who are candidates for thrombolytic therapy.Case presentationWe report the case of a 71-year-old hypertensive Caucasian woman with non-valvular atrial fibrillation treated with dabigatran 150 mg twice daily, who presented with acute ischemic stroke causing right-sided hemiparesis and aphasia. Two hours after presentation to the emergency department, a decision was made to administer idarucizumab for achieving complete reversal of any potential anticoagulant effect of dabigatran and, in the absence of any contraindications, our patient underwent successful thrombolysis. At discharge, our patient was able to walk unassisted and had only residual aphasia. Twenty days later, she had completely recovered motor function of her right side, with further progressive improvement of aphasia. Repeat cranial computed tomography confirmed the absence of hemorrhage, and anticoagulant therapy with dabigatran 150 mg twice daily was resumed.ConclusionsOur case report adds to the evidence that idarucizumab administration is safe in the setting of patients with atrial fibrillation treated with dabigatran who develop acute ischemic stroke requiring thrombolysis.