Clinical-DNA Correlates of Anxiety in Patients with Ehlers-Danlos Syndrome

Introduction: Anxiety disorders have a lifetime prevalence of 34% with a similar level of heritability (31%) yet lack objective markers that could differentiate patients with underlying conditions. Up to 60%-70% of patients with Ehlers-Danlos syndrome have anxiety that meets criteria of generalized anxiety disorder, their clinical-DNA findings worth examining as biomarkers for patients with generalized anxiety. Method: Of the 1899 patients diagnosed with Ehlers-Danlos syndrome, 1261 were systematically evaluated for 80 history and 40 physical findings and separated into 826 who reported anxiety and 435 who did not. The most consistently reported or management-directing 60 of these clinical findings were, along with variations in genes relevant to these disorders, examined for association with anxiety. Results: Among the 30 anxiety- associated findings judged most predictive of Ehlers-Danlos syndrome in patients with anxiety were expected ones of adrenergic stimulation (difficulty concentrating-87% frequency and 1.26 anxiety/no anxiety ratio;chronic fatigue-84%, 1.17;sleep issues 69%, 1.52 that are criteria for generalized anxiety disorder) or of cholinergic suppression (e.g., frequent nausea 64%, 1.26). Less associated but more discriminating for underlying disease were those reflective of neuromuscular impact (e.g., chronic daily headaches 76%, 1.12);hypermobility (e.g., awareness of flexibility 72%, 1.03), or skin changes (e.g., elasticity around jaw 71%, 1.06). Anxiety-associated DNA variants included 54 of 88 in collagen type I/V/VII/IX genes, 14 of 16 in sodium channel SCN9A/10A/ 11A genes, 59 of 85 in POLG/MT-DNA genes, and 21 of 28 in profilaggrin- FLG genes that respectively impacted tissue laxity, sensory neural, autonomic-mitochondrial, and autonomic-inflammatory functions. Conclusion: Analysis of pathogenetic mechanisms in Ehlers-Danlos syndrome selected some 50 clinical-DNA findings useful for its diagnosis in those with generalized anxiety disorders.

Prevalence and risk factors for acquired long QT syndrome in the emergency department:a retrospective observational study

BACKGROUND: Long QT syndrome(LQTS) is a heterogeneous syndrome that may be congenital or, more frequently, acquired. The real-world prevalence of acquired LQTS(aLQTS) in the emergency department(ED) remains to be determined. The aim of this study was to determine prevalence of aLQTS and its impact on symptoms on ED admissions.METHODS: Electrocardiograms(ECG) of 5,056 consecutively patients admitted in the ED of a tertiary hospital between January 28th and March 17th of 2020 were reviewed. All patients with aLQTS were included. Clinical data with a focus on QT prolonging drugs and clinical factors were recorded. Statistical comparison was made between the groups with and without corrected QT(QTc) interval greater than 500 ms(value that is considered severely increased).RESULTS: A total of 383 ECGs with prolonged QTc were recognized, corresponding to a prevalence of aLQTS at admission of 7.82%. Patients with aLQTS were more commonly men(53.3%) with an age of(73.49±14.79) years old and QTc interval of(505.3±32.4) ms. Only 20.4% of these patients with aLQTS were symptomatic. No ventricular arrhythmias were recorded. Patients with QT interval greater than 500 ms were more frequently female(59.5%;P<0.001) and were more frequently on QT prolonging drugs(77.3%;P=0.025). Main contributing factor was intake of antibiotics(odds ratio [OR] 4.680) followed by female gender(OR 2.473) and intake of antipsychotics(OR 1.925).CONCLUSION: aLQTS is particularly prevalent in the ED. Female patients on antibiotics and antipsychotics are at particularly high risk. Efforts must be made to avoid, detect and treat aLQTS as early as possible.

Inflammatory/immune-suppressive microenvironment characteristics of pancreatic cancer patients with Shi-Re syndrome identified by extracellular vesicle long RNA profiling

Background:Numerous long RNAs were detected in extracellular vesicles(EVs),some of which were related with the tissue origins and immune cell types.This study examined the molecular basis of different traditional Chinese medicine syndrome diagnoses(also called syndrome differentiation)in pancreatic ductal adenocarcinoma.Methods:128 pancreatic ductal adenocarcinoma patients with different syndrome diagnoses were retrospectively reviewed in this study.Long RNA sequencing was conducted to analyze the EV long RNA profile of plasma samples.Differentially regulated EV long RNAs were annotated and assessed for Gene Ontology pathway enrichment using DAVID.The online program xCell were used to perform the cell-type enrichment analysis.Results:An average of 15,000 annotated genes,mainly including messenger RNAs,were stably detected per sample.Different syndrome diagnoses exhibited unique EV mRNA expression profiles and therefore different enriched pathways.Gene Set Enrichment Analysis discovered transforming growth factor-βand kirsten rat sarcoma viral oncogene homolog signaling activation as the hallmarks of cancer with Shi-Re syndrome.Cell-type enrichment analysis also revealed a varied inflammation/immune cell type distribution among patients with or without Shi-Re diagnosis.Mast cells,platelets and Tregs were significantly enriched but basophils,common lymphoid progenitors,dendritic cells,and conventional dendritic cells were decreased in patients with Shi-Re diagnosis compared with patients without Shi-Re diagnosis.Conclusion:We identified the hallmarks of cancer with different syndrome diagnoses based on plasma EV long RNA sequencing.In particular,transforming growth factor-βand kirsten rat sarcoma viral oncogene homolog signaling activation were the hallmarks of Shi-Re syndrome,which contribute to shape an inflammatory/immune-suppressive tumor microenvironment in pancreatic ductal adenocarcinoma.

Nasogastric tube syndrome induced by an indwelling long intestinal tube

The nasogastric tube(NGT) has become a frequently used device to alleviate gastrointestinal symptoms. Nasogastric tube syndrome(NTS) is an uncommon but potentially life-threatening complication of an indwelling NGT. NTS is characterized by acute upper airway obstruction due to bilateral vocal cord paralysis. We report a case of a 76-year-old man with NTS, induced by an indwelling long intestinal tube. He was admitted to our hospital for treatment of sigmoid colon cancer. He underwent sigmoidectomy to release a bowel obstruction, and had a long intestinal tube inserted to decompress the intestinal tract. He presented acute dyspnea following prolonged intestinal intubation, and bronchoscopy showed bilateral vocal cord paralysis. The NGT was removed immediately, and tracheotomy was performed. The patient was finally discharged in a fully recovered state. NTS be considered in patients complaining of acute upper airway obstruction, not only with a NGT inserted but also with a long intestinal tube.

Drugs to be avoided in patients with long QT syndrome:Focus on the anaesthesiological management

Long QT syndrome incidence is increasing in general population.A careful pre-,peri-and post-operative management is needed for patients with this syndrome because of the risk of Torsades de Pointes and malignant arrhythmias.The available data regarding prevention of lethal Torsades de Pointes during anesthesia in patients with long QT syndrome is scant and conflicting:only case reports and small case series with different outcomes have been published.Actually,there are no definitive guidelines on pre-,peri-and post-operative anesthetic management of congenital long QT syndrome.Our review focuses on anesthetic recommendations for patients diagnosed with congenital long QT syndrome furnishing some key points for preoperative optimization,intraoperative anesthetic agents and postoperative care plan,which could be the best for patients with c-long QT syndrome who undergo surgery.

Delayed inflammatory pulmonary syndrome: A distinct clinical entity in the spectrum of inflammatory syndromes in COVID-19 infection?

BACKGROUND During the second wave of the coronavirus disease 2019(COVID-19)pandemic,a subset of critically ill patients developed delayed respiratory deterioration in the absence of new infection,fluid overload or extra-pulmonary organ dysfunction.AIM To describe the clinical and laboratory characteristics,outcomes,and management of these patients,and to contrast this entity with other post COVID-19 immune dysregulation related inflammatory disorders.METHODS This was a retrospective observational study of adult patients admitted to the medical intensive care unit of a 2200-bed university affiliated teaching hospital,between May and August 2021,who fulfilled clearly defined inclusion and exclusion criteria.Outcome was assessed by a change in PaO_(2)/FiO_(2) ratio and levels of inflammatory markers before and after immunomodulation,duration of mechanical ventilation after starting treatment,and survival to discharge.RESULTS Five patients developed delayed respiratory deterioration in the absence of new infection,fluid overload or extrapulmonary organ dysfunction at a median interquartile range(IQR)duration of 32(23-35)d after the onset of symptoms.These patients had elevated inflammatory markers,required mechanical ventilation for 13(IQR 10-23)d,and responded to glucocorticoids and/or intravenous immunoglobulin.One patient died(20%).CONCLUSION This delayed respiratory worsening with elevated inflammatory markers and clinical response to immunomodulation appears to contrast the well described Multisystem Inflammatory Syndrome–Adults by the paucity of extrapulmonary organ involvement.The diagnosis can be considered in patients presenting with delayed respiratory worsening,that is not attributable to cardiac dysfunction,fluid overload or ongoing infections,and associated with an increase in systemic inflammatory markers like C-reactive protein,inteleukin-6 and ferritin.A good response to immunomodulation can be expected.This delayed inflammatory pulmonary syndrome may represent a distinct clinical entity in the spectrum of inflammatory syndromes in COVID-19 infection.

Genotypic diagnosis of long QT syndrome by analysis of candidate genes

Objective To diagnose 6 LQTS families by genetic analysis.Methods A total aof 6 LQTS pedigrees with 43 family members were brought together for genetic diagnosis by using short-sequence tandem-repeat(STR)markers or sequencing.Genomic DNA was extracted from blood samples by standard procedure.STR markers or KCNQ1,KCNH2 and SCN5A were amplified.The haplotype analysis for LQTS was performed.If the family got the negative haplotype analysis,the sequencing was performed.Results LQTS patients were always linkaged with the SCN5A gene in family 1.KCNH2 was linkaged with the disease in family 2 to 5.21 gene carriers were identified from these 5 families.A mutation(A561V-KCNH2)was only found in the proband of family 6 and an SNP(G1691A)was found in all the members of the family.Conclusion Genetic diagnosis can not only improve presymptomatic diagnosis,but also provide the basis for personal therapy and research on disease-causing mutations.

A novel mutation—L539fs/47 of hERG in a Chinese long QT syndrome family

Objective To identify the mutation of human ether-a-go-go-related gene(hERG)and analyze the clinical characteristics of a Chinese family with long ST syndrome(LQTS).Methods The electrocardiogram and DNA samples were obtained from a Chinese LQTS family of 26 members.Genotype was performed with polymorphic short tandem repeat(STR)markers at the known LQT1,LQT2,and LQT3 loci.SSCP analysis was used to find aberrant conformers.hERG mutation was confirmed by cloning and sequencing.Results Three gene carriers were linked to chromosome 7q35-36,where the potassium channel gene hERG was encoded.A 19-base pair deletion was identified.The mutation was located at nucleotide position 1 619-1 637 between transmembrane domains S4 and S5.Furthermore,A1692G polymorphism was found both in the normal control and patients.Conclusion A novel 19 bp deletion mutation of hERG is identified in a Chinese family.All gene carriers are demonstrated to be typical LQT2 ECG phenotype.

A novel splice mutation of HERG in a Chinese family with long QT syndrome

Congenital long QT syndrome (LQTS) is a genetically heterogeneous disease in which six ion-channel genes have been identified. The phenotype-genotype relationships of the HERG (human ether-a-go-go-related gene) mutations are not fully understood. The objective of this study is to identify the underlying genetic basis of a Chinese family with LQTS and to characterize the clinical manifestations properties of the mutation. Single strand conformation polymorphism (SSCP) analyses were conducted on DNA fragments amplified by polymerase chain reaction from five LQT-related genes. Aberrant conformers were analyzed by DNA sequencing. A novel splice mutation in C-terminus of HERG was identified in this Chinese LQTS family,leading to the deletion of 11-bp at the acceptor splice site of Exon9 [Exon9 IVS del (-12→-2)]. The mutation might affect,through deficient splicing, the putative cyclic nucleotide binding domain (CNBD) of the HERG K+ channel. This mutation resulted in a mildly affected phenotype. Only the proband had a history of syncopes, while the other three individuals with long QT interval had no symptoms. Two other mutation carriers displayed normal phenotype. No sudden death occurred in the family. The 4 affected individuals and the two silent mutation carriers were all heterozygous for the mutation. It is the first splice mutation of HERG reported in Chinese LQTS families. Clinical data suggest that the CNBD mutation may be less malignant than mutations occurring in the pore region and be partially dominant over wild-type function.

Diagnosis of long QT syndrome via support vector machines classification

Congenital Long QT Syndrome (LQTS) is a genetic disease and associated with significant arrhythmias and sudden cardiac death. We introduce a noninva-sive procedure in which Discrete Wavelet Trans-form (DWT) is used to extract features from elec-trocardiogram (ECG) time-series data first, then the extracted features data is classified as either abnormal or unaffected using Support Vector Machines (SVM). A total of 26 genetically identified patients with LQTS and 19 healthy controls were studied. Due to the limited number of samples, model selection was done by training 44 instances and testing it on remaining one in each run. The proposed method shows reasonably high average accuracy in LQTS diagnosis when combined with best parameter selection process in the classifica-tion stage. An accuracy of 80%is achieved when Sigmoid kernel is used in v-SVM with parameters v = 0.58 and r = 0.5. The corresponding SVM model showed a classification rate of 21/26 for LQTS pa-tients and 15/19 for controls. Since the diagnosis of LQTS can be challenging, the proposed method is promising and can be a potential tool in the correct diagnosis. The method may be improved further if larger data sets can be obtained and used.

The Relationship between T-Wave Alternans and Adverse Cardiac Events in Patients with Congenital Long QT Syndrome:A Systematic Review and Meta-Analysis

Background:T-wave alternans(TWA)is a risk factor of ventricular arrhythmias or sudden cardiac death(SCD)in patients with ischemic cardiomyopathy.Nevertheless,the relationship between TWA and adverse cardiac events(ACE)in patients with congenital long QT syndrome(LQT)remains controversial.Methods:A systematic electronic search of PubMed,Embase and the Cochrane Library was conducted from database inception dates to 28 April 2021 and assessed the relationship between TWA and ACE in patients with LQTS.Sub-group analysis evaluated the association between microvolt TWA(MTWA)and ACE in different monitoring models and ECGlead numbers.Results:A pooled analysis of seven studies of 625 patients with LQTS showed that TWA was significantly associated with ACE(OR 3.16,95%CI 1.86–5.37,P<0.001).Advanced analysis showed that macroscopic TWA was significantly related to ACE(OR 6.01,95%CI 2.96–12.21,P<0.001),while MTWA did not(OR 0.92,95%CI 0.37–2.30,P=0.85).Sub-group analysis showed that MTWA recorded in 24 h continuous ECG(OR 6.79,95%CI 0.80–57.75,P=0.08)might have a stronger association with ACE than recorded in stress ECG(OR 0.28,95%CI 0.07–1.10,P=0.07).No difference was observed between MTWA measured in multi-lead ECG and limited ECG leads(P=0.15).Conclusions:Macroscopic TWA was significantly related to ACE in patients with LQTS.In terms of MTWA,MTWA recorded in 24 h continuous ECG might have a stronger association with ACE than stress ECG,but still deserves further evaluation.

Discovery of Digenic Mutation, KCNH2 c.1898A > C and JUP c.916dupA, in a Chinese Family with Long QT Syndrome via Whole-Exome Sequencing

Long QT syndrome(LQTS),which is caused by an ion channel–related gene mutation,is a malignant heart disease with a clinical course of a high incidence of ventricular fi brillation and sudden cardiac death in the young.Mutations in KCNH2(which encodes potassium voltage-gated channel subfamily H member 2)are responsible for LQTS in many patients.Here we report the novel mutation c.1898A>C in KCNH2 in a Chinese family with LQTS through whole-exome sequencing.The c.916dupA mutation in JUP(which encodes junction plakoglobin)is also discovered.Mutations in JUP were found to be associated with arrhythmogenic right ventricular cardiomyopathy.The double mutation in the proband may help explain his severe clinical manifestations,such as sudden cardiac death at an early age.Sequencing for the proband’s family members revealed that the KCNH2 mutation descends from his paternal line,while the mutation in JUP came from his maternal line.The data provided in this study may help expand the spectrum of LQTS-related KCNH2 mutations and add support to the genetic diagnosis and counseling of families affected by malignant arrhythmias.

Preventive and therapeutic effect of long snake moxibustion on psoriasis with yang deficiency and external cold syndrome based on the theory of "treatment of winter disease in summer"

Psoriasis is a chronic inflammatory skin disease with multiple layers of silvery white scales on the surface of erythema papule as the main clinical characteristics,of which yang-deficiency external cold psoriasis is refractory,recurrent and severe in winter and mild in summer,which has a great impact on patients'physical and mental health and quality of life.Traditional Chinese medicine has unique insights in the treatment of psoriasis,both curative effect and safety,have obvious advantages.Based on the concept of"winter disease and summer treatment",long-snake moxibustion gives full play to its functions of warming the kidney,invigorating the marrow,warming the meridians,activating blood circulation and removing blood stasis,so as to restore the deficiency of Yang in patients with psoriasis with external cold syndrome,enhance disease resistance,and prevent psoriasis recurrence or aggravation in winter.Therefore,based on the theory of"winter disease and summer treatment",this paper preliminarily discusses the mechanism of long-snake moxibustion in the prevention and treatment of psoriasis with external cold syndrome of Yang deficiency,and provides new ideas and directions for the prevention and treatment of psoriasis with traditional Chinese medicine.

Effect of Calcium-Channel Antagonist on Repolarization Heterogeneity of Ventricular Myocardium in an in Vitro Rabbit Model of Long QT Syndrome

Intracellular Ca2＋ and Ca2＋-dependent signaling molecule play an essential role in the genesis of long-QT （LQT） syndrome-related ventricular arrhythmias. The effect of calcium-channel antagonist verapamil on repolarization heterogeneity of ventricular myocardium was assessed in an in vitro rabbit model of LQT syndrome. By using the monophasic action potential （MAP） recording technique, MAPs of epicardium, mid-myocardium and endocardium were simultaneously recorded by specially designed plunge-needle electrodes across the left ventricular free wall in rabbit hearts purfused by Langendorff method with standard Tyrode＇s solution. Bradycardia was induced by com- plete ablation of atrioventricular node. A catheter was introduced into the right ventricle to pace at the cycle lengths （CLs） of 1500, 1000, and 500 ms, successively. Quinidine （2 μmol/L） prolonged QT interval and ventricular MAP duration （MAPD）, and increased transmural dispersion of repolarization （TDR） in a reverse rate-dependent fashion in isolated rabbit heart. No polymorphic ventricular tachycardias were induced under this condition. The effective free therapeutic plasma concentrations of verapamil （0.01--0.05μmol/L） used in this experiment had no effect on quinidine-induced changes of QT interval, MAPD and TDR. This study demonstrated that, in this model of LQT syndrome, blockade of calcium-channel with verapmil had no effect on quinidine-induced changes of repolatiation heterogeneity of ventricular myocardium.

Non genetic risk factors of long-QT syndrome

The purpose of the present study is to provide guidelines regarding risk factors that may worsen the Long-QT Syndrome (LQTS), based on available literature. This review evaluates the current knowledge on these risk factors of acquired LQTS, with an emphasis on non genetic risk factors, including environmental factors. PubMed was searched for literature in English from 1999 to 2011 on the molecular and clinical studies of Long-QT syndrome. We agree, with recent investigations described in the literature, that variety of factors, inherited or environmental, can influence expression of ion channel proteins with impact on repolarization.

The Novel Long QT Syndrome Type 2-associated F129I Mutation in the KCNH2 Gene Significantly Affects IKr Through the hERG1 Homomeric and Heteromeric Potassium Channels

Objective:The long QT syndrome type 2 is caused by the loss-of-function mutations in the KCNH2 gene,which encodes hERG1,the voltage-gated potassium channel.The hERG1 channels conduct rapid delayed rectifier K^(+)currents(I_(Kr))in the human cardiac tissue.KCNH2 encodes 2 main isoforms-hERG1a and hERG1b,which assemble to form the homomeric or heteromeric hERG1 channels.However,the functional characteristics of the heteromeric hERG1 channels in long QT syndrome type 2 are not clear.In this study,a novel mutation in the N-terminus of hERG1a(F129l)was identified in a proband of long QT syndrome type 2.The purpose of this study was to identify the electrophysiological change of homomeric and heteromeric hERG1 channels with theF129l-hERG1a.Methods:Candidate genes were screened by direct sequencing.F129l-hERG1a was cloned in the pcDNA3.1 vector by site-directed mutagenesis.Then,the wild-type(WT)hERG1a and/or F129l-hERG1a were transiently expressed in the HEK293 cells with or without hERG1b co-expression.The expression levels of the transgenes,cellular distribution of hERG1a and hERG1b,and the electrophysiological features of the homomeric and the heteromeric hERG1 channels with the WT-hERG1a or F129l-hERG1a were analyzed using whole-cell patch-clamp electrophysiology,western blotting,and immunofluorescence techniques.Results:The proband was clinically diagnosed with long QT syndrome type 2 and carried a heterozygous mutation c.385T>A(F1291)in the KCNH2 gene.Electrophysiology study proved that the F129l substitution in hERG1a significantly decreased I_(Kr) in both the homomeric and heteromeric hERG1channels by 86%and 70%,respectively(WT-hERG1a(54.88±18.74)pA/pF vs.F129l-hERG1a(7.34±1.90)pA/pF,P<0.001;WT-hERG1a/hERG1b(89.92±24.51)pA/pF vs.F129l-hERG1a/hERG1b(26.54±9.83)pA/pF,P<0.001).The voltage dependence of I_(Kr) activation(V_(1/2) and k)was not affected by the mutation in both the homomeric and heteromeric hERG1 channels.The peak current densities and the kinetic characteristics of I_(Kr) were comparable for both WT/F129l-hERG1a and WT-hERG1a.The channel inactivation and deactivation analysis showed that F129l substitution did not affect deactivation of the homomeric hERG1a channel,but significantly accelerated the deactivation and recovery from inactivation of the heteromeric hERG1a/hERG1b channel based on the time constants of fast and slow recovery from deactivation F129l-hERG1a/hERG1b vs.WT-hERG1a/hERG1b(P<0.05).Western blotting and immunofluorescence labeling experiments showed that maturation and intracellular trafficking of the F129l-hERG1a protein was impaired and potentially increased the ratio of hERG1b to hERG1a in the F129l-hERG1a/hERG1b tetramer channel,thereby resulting in electrophysiological changes characteristic of the long QT syndrome type 2 pathology.Conclusions: I_(Kr) Was significantly reduced in the homomeric and heteromeric hERG1 channels with F129l-hERG1a.The F129l mutation significantly accelerated the deactivation and recovery from inactivation of the heteromeric F129l-hERG1a/hERG1b channel.F129l-hERG1a exhibited impaired maturation and intracellular trafficking,thereby potentially increasing the ratio of the hERG1b to hERG1a stoichiometry in the hERG1 tetrameric channel.These changes demonstrated the importance of the heteromeric hERG1 channel in long QT syndrome type 2 pathophysiology.

Polycystic ovary syndrome patients with high BMI tend to have functional disorders of androgen excess:a prospective study

Biochemical or clinical changes of hyperandrogenism are important elements of polycystic ovary syndrome （PCOS）. There is currently no consensus on the definition and diagnostic criteria of hyperandrogenism in PCOS. The aim of this study was to investigate the complex symptoms of hyperandrogenic disorders and the correlations between metabolism and hyperandrogenism in patients with PCOS from an outpatient reproductive medicine clinic in China. We conducted a case control study of 125 PCOS patients and 130 controls to evaluate differences in body mass index （BMI）, total testosterone （TT）, modified Ferriman-Gallwey hirsutism score, sex hormone binding globulin （SHBG）, homeostasis model assessment-estimated insulin resistance （HOMA-IR） and free androgen index （FAI） between PCOS patients and controls and subgroups of PCOS. The prevalence of acne and hirsutism did not differ significantly between the hyperandrogenic and non-hyperandrogenic subgroup. Patients with signs of hyper- androgenism had significantly higher BMI （P 〈 0.05）, but differences in TT, SHBG, FAI and waist/hip ratio were insignificant. The odds ratio of overweight was calculated for all PCOS patients. Our results suggest that PCOS patients with high BMI tend to have functional disorders of androgen excess; therefore, BMI may be a strong pre-dictor of hyperandrogenism in PCOS.

Main factors influencing long-term outcomes of liver transplantation in 2022

Liver transplant(LT)outcomes have markedly improved in the recent decades,even if long-term morbidity and mortality are still considerable.Most of late deaths are independent from graft function and different comorbidities,including complications of metabolic syndrome and de novo neoplasms,seem to play a key role in determining long-term outcomes in LT recipients.This review discusses the main factors associated with late mortality and suggests possible strategies to improve long-term management and follow-up after liver transplantation.In particular,the reduction of drug toxicity,the use of tools to identify high-risk patients,and setting up a multidisciplinary team also for long-term management of LT recipients may further improve survival after liver transplantation.

Fat Embolism Syndrome in a Patient with Bilateral Tibial Fractures: Report of the Case and Review of the Literature

Background: Although the original clinical description of fat embolism syndrome (FES) dates from 1873, the condition remains a diagnostic challenge for modern clinicians. The syndrome is described as a serious consequence of fat emboli producing a distinct pattern of clinical symptoms and signs. It is mainly associated with fractures of the long-bones and the pelvis. The present paper describes the case of a trauma patient with bilateral tibial fractures that present the syndrome and highlights the importance of early identification and aggressive treatment of FES which is obligatory for the patient’s survival. Case Description: A 32 year-old man reached the hospital as a trauma call after a road traffic accident. Clinical examination was unremarkable with the only finding that the patient was unable to straight leg raise and weight bear. Both shins were painful and swollen at their middle third, while the left one was in varus and posterior displacement. Neurovascular status of both lower extremities was normal. Plain radiographic control (X-Rays) revealed an oblique right tibial fracture of the mid-shaft with a distal third fibular fracture and a comminuted fracture of the left tibia with a fracture of the fibula at the same level. The legs were immobilised on a splint and the decision was to treat the patient surgically. Within a few post admission hours the haemoglobin dropped by 2.9 mg/dL, however a source of active bleeding could not be allocated. The abdomen was soft and not tender in palpation and the central nervous system did not present any abnormalities. The following day the haemoglobin dropped but the new ultrasonography control did not reveal any free abdominal fluid. Both lower limbs were not compromised. The second post-injury day the patient went to theatre and the right tibia was stabilised with an antegrade nail (T2-Stryker) while the left one with an external fixation. During the reaming process the haemoglobin dropped to 7.1 gr/dL, so he was transfused with 3 blood units. Immediately after extubation, the patient desaturated on air and ABG values forced the anaesthetists to intubate him in recovery and place him in mechanical ventilation with high levels of positive end expiratory pressure (PEEP). Symptoms subsided rapidly and he was transferred to the IMU. Clinical image and CT scan were in favour of fat embolism syndrome. On the fifth post-operative day the patient was transferred back to ward and a week later he was discharged being completely free of symptoms. Clinical Relevance: Fat embolism syndrome is typically presented with the following triad: a) respiratory changes;b) neurologic abnormalities;c) petechial rash. These three constitute the major criteria described by Gurd and are pathognomonic for the condition. The patient—described in the present case report—developed progressively all those symptoms within the expected period of time. The FES is a well-known pathological condition that is well described in literature and should be familiar to those clinicians that manage trauma patients. Diagnosing the condition can be highly demanding since there are no laboratory investigations or radiographic imaging techniques specific for FES. Suspicion and diagnosis can be mainly placed based on the criteria described by Gurd, in 1970.

Slow and Steady: The Cautious Use of Neuroleptics in a Patient with Andersen-Tawil Syndrome

Long QT syndrome (LQT) is a disease of cardiac repolarization caused by alterations in the transmembrane potassium and sodium currents. This results in prolongation of the QT interval on electrocardiography (EKG) and can result in torsade de pointes and sudden cardiac death. We present a case of a patient who has Anderson Tawil syndrome;a congenital long QT syndrome, with a history of cardiac arrhythmias who developed acute paranoid schizophrenia that was refractory to treatment with non-QT-prolonging drugs and required institution of neuroleptics to control her psychiatric symptoms.