Interleukin 1βreceptor and synaptic dysfunction in recurrent brain infection with Herpes simplex virus type-1

Several experimental evidence suggests a link between brain Herpes simplex virus type-1 infection and the occurrence of Alzheimer’s disease.However,the molecular mechanisms underlying this association are not completely understood.Among the molecular mediators of synaptic and cognitive dysfunction occurring after Herpes simplex virus type-1 infection and reactivation in the brain neuroinflammatory cytokines seem to occupy a central role.Here,we specifically reviewed literature reports dealing with the impact of neuroinflammation on synaptic dysfunction observed after recurrent Herpes simplex virus type-1 reactivation in the brain,highlighting the role of interleukins and,in particular,interleukin 1βas a possible target against Herpes simplex virus type-1-induced neuronal dysfunctions.

Quantitative assessment of self-management in patients with nonalcoholic fatty liver disease: An unmet clinical need

In this editorial we comment on the article titled“Establishment and validation of an adherence prediction system for lifestyle interventions in non-alcoholic fatty liver disease”by Zeng et al published in a recent issue of the World Journal of Gastroenterology.Non-alcoholic fatty liver disease(NAFLD)represents one of the current challenges in hepatology and public health,due to its continuous growing prevalence and the rising incidence of NAFLD-related fibrosis,non-alcoholic steatohepatitis and cirrhosis.The only effective therapeutic strategy for this dis-ease is represented by encouraging patients to improve their lifestyle through the modification of dietary intake and increased physical exercise,but the effective application of such modifications is often limited by various factors such as lack of information,psychological barriers or poor social support.While poor adherence to a healthy lifestyle can be decisive in determining the clinical outcome,in daily practice there is a lack of quantitative instruments aimed at identifying patients with the lowest adherence to lifestyle changes and higher risk of disease progre-ssion in the course of follow-up.In this article,Zeng et al propose a quantitative scale to assess the grade of adherence of patients with NAFLD to hea-lthy lifestyle intervention,called the Exercise and Diet Adherence Scale(EDAS).This scale,consisting of 33 items divided into 6 dimensions which relates to six subjective aspects in the self-management of NAFLD,has shown a good correlation with the identification of the sub-cohort of patients with the highest reduction in caloric intake,increase in physical exercise,probability of a reduction in liver stiffness measurement and alanine aminotransferase levels.The cor-relation among clinical outcomes and specific dimensions of this scale also highlights the pivotal role of a good and confidential doctor-patient relationship and of an effective communication.There is an urgent need for practical and effective instruments to assess the grade of self-management of NAFLD patients,together with the development of multidisciplinary teams with the aim of applying structured behavioral interventions.

Driving pressure:A useful tool for reducing postoperative pulmonary complications

The operating room is a unique environment where surgery exposes patients to non-physiological changes that can compromise lung mechanics.Therefore,raising clinicians’awareness of the potential risk of ventilator-induced lung injury(VILI)is mandatory.Driving pressure is a useful tool for reducing lung complications in patients with acute respiratory distress syndrome and those undergoing elective surgery.Driving pressure has been most extensively studied in the context of single-lung ventilation during thoracic surgery.However,the awareness of association of VILI risk and patient positioning(prone,beach-chair,parkbench)and type of surgery must be raised.

Portal vein thrombosis in cirrhosis: Why a well-known complication is still matter of debate

Portal vein thrombosis(PVT)represents a well-known complication during the natural course of liver cirrhosis(LC),ranging from asymptomatic cases to lifethreating conditions related to portal hypertension and hepatic decompensation.Portal flow stasis,complex acquired hypercoagulable disorders and exogenous factors leading to endothelial dysfunction have emerged as key factors for PVT development.However,PVT occurrence remains unpredictable and many issues regarding its natural history,prognostic significance and treatment are still elusive.In particular although spontaneous resolution or disease stability occur in most cases of PVT,factors predisposing to disease progression or recurrence after spontaneous recanalization are not clarified as yet.Moreover,PVT impact on LC outcome is still debated,as PVT may represent itself a consequence of liver fibrosis and hepatic dysfunction progression.Anticoagulation and transjugular intrahepatic portosystemic shunt are considered safe and effective in this setting and are recommended in selected cases,even if the safer therapeutic option and the optimal therapy duration are still unknown.Nevertheless,their impact on mortality rates should be addressed more extensively.In this review we present the most debated questions regarding PVT,whose answers should come from prospective cohort studies and large sample-size randomized trials.

Oral frailty and neurodegeneration in Alzheimer’s disease

Frailty is a critical intermediate status of the aging process with a multidimensional and multisystem nature and at higher risk for adverse health-related outcomes,including falls,disability,hospitalizations,institutionalization,mortality,dementia,and Alzheimer’s disease.Among different frailty phenotypes,oral frailty has been recently suggested as a novel construct defined as a decrease in oral function with a coexisting decline in cognitive and physical functions.We briefly reviewed existing evidence on operational definitions of oral frailty,assessment and screening tools,and possible relationships among oral frailty,oral microbiota,and Alzheimer’s disease neurodegeneration.Several underlying mechanism may explain the oral health-frailty links including undernutrition,sarcopenia linked to both poor nutrition and frailty,psychosocial factors,and the chronic inflammation typical of oral disease.Oral microbiota may influence Alzheimer’s disease risk through circulatory or neural access to the brain and the interplay with periodontal disease,often causing tooth loss also linked to an increased Alzheimer’s disease risk.On this bases,COR388,a bacterial protease inhibitor targeting Porphyromonas gingivalis implicated in periodontal disease,is now being tested in a double-blind,placebocontrolled Phase II/III study in mild-to-moderate Alzheimer’s disease.Therefore,oral status may be an important contributor to general health,including Alzheimer’s disease and latelife cognitive disorders,suggesting the central role of preventive strategies targeting the novel oral frailty phenotype and including maintenance and improvement of oral function and nutritional status to reduce the burden of both oral dysfunction and frailty.

Intestinal permeability after Mediterranean diet and low-fat diet in non-alcoholic fatty liver disease

BACKGROUND In non-alcoholic fatty liver disease(NAFLD), a high-fat or high-fructose diet increases intestinal permeability and promotes derangement of the gut-liver axis.We hypothesize that, diet could be able to modulate intestinal permeability in patients with NAFLD.AIM To detect diet-induced modification of intestinal permeability in patients with NAFLD undergoing a Mediterranean diet or a low-fat diet.METHODS The current study was a dietary intervention for non-diabetic, patients with biopsy-verified NAFLD and increased transaminases. A crossover design was employed: participants underwent 16 weeks of Mediterranean diet, 16 wk of free wash-out, and 16 weeks of low-fat diet. Both diets were hypocaloric and no consumption of supplements was allowed. All patients were followed bimonthly by a dietitian. Evaluations of clinical and metabolic parameters were completed at baseline and at the end of each dietary period. Intestinal permeability was assessed by chromium-51 ethylene diamine tetraacetate excretion testing(51 CrEDTA).RESULTS Twenty Caucasian patients, 90% male, median age 43 years, body mass index(BMI) 30.9, with biopsy-verified NAFLD were enrolled. At the end of 16 weeks of a Mediterranean diet, a significant reduction in mean body weight(-5.3 ± 4.1 kg,P = 0.003), mean waist circumference(-7.9 ± 4.9 cm, P = 0.001), and mean transaminase levels [alanine aminotransferase(ALT)-28.3 ± 11.9 IU/L, P =0.0001; aspartate aminotransferase(AST)-6.4 ± 56.3 IU/L, P = 0.01] were observed. These benefits were maintained after 16 wk of wash-out and also after16 wk of low-fat diet, without further improvements. Fourteen of the 20 patients had intestinal permeability alteration at baseline(mean percentage retention of51 Cr-EDTA = 5.4%), but no significant changes in intestinal permeability were observed at the end of the 16 wk of the Mediterranean diet or 16 wk of the low-fat diet.CONCLUSION Mediterranean diet is an effective strategy for treating overweight, visceral obesity and serum transaminase in patients with NAFLD. If the Mediterranean diet can improve intestinal permeability in patients with NAFLD, it deserves further investigation.

Contrast-enhanced ultrasound Liver Imaging Reporting and Data System:Lights and shadows in hepatocellular carcinoma and cholangiocellular carcinoma diagnosis

BACKGROUND Contrast-enhanced ultrasound(CEUS)is considered a secondary examination compared to computed tomography(CT)and magnetic resonance imaging(MRI)in the diagnosis of hepatocellular carcinoma(HCC),due to the risk of misdiagnosing intrahepatic cholangiocarcinoma(ICC).The introduction of CEUS Liver Imaging Reporting and Data System(CEUS LI-RADS)might overcome this limitation.Even though data from the literature seems promising,its reliability in real-life context has not been well-established yet.AIM To test the accuracy of CEUS LI-RADS for correctly diagnosing HCC and ICC in cirrhosis.METHODS CEUS LI-RADS class was retrospectively assigned to 511 nodules identified in 269 patients suffering from liver cirrhosis.The diagnostic standard for all nodules was either biopsy(102 nodules)or CT/MRI(409 nodules).Common diagnostic accuracy indexes such as sensitivity,specificity,positive predictive value(PPV),and negative predictive value(NPV)were assessed for the following associations:CEUS LR-5 and HCC;CEUS LR-4 and 5 merged class and HCC;CEUS LR-M and ICC;and CEUS LR-3 and malignancy.The frequency of malignant lesions in CEUS LR-3 subgroups with different CEUS patterns was also determined.Inter-rater agreement for CEUS LI-RADS class assignment and for major CEUS pattern identification was evaluated.RESULTS CEUS LR-5 predicted HCC with a 67.6%sensitivity,97.7%specificity,and 99.3%PPV(P<0.001).The merging of LR-4 and 5 offered an improved 93.9%sensitivity in HCC diagnosis with a 94.3%specificity and 98.8%PPV(P<0.001).CEUS LR-M predicted ICC with a 91.3%sensitivity,96.7%specificity,and 99.6%NPV(P<0.001).CEUS LR-3 predominantly included benign lesions(only 28.8%of malignancies).In this class,the hypo-hypo pattern showed a much higher rate of malignant lesions(73.3%)than the iso-iso pattern(2.6%).Inter-rater agreement between internal raters for CEUS-LR class assignment was almost perfect(n=511,k=0.94,P<0.001),while the agreement among raters from separate centres was substantial(n=50,k=0.67,P<0.001).Agreement was stronger for arterial phase hyperenhancement(internal k=0.86,P<2.7×10-214;external k=0.8,P<0.001)than washout(internal k=0.79,P<1.6×10-202;external k=0.71,P<0.001).CONCLUSION CEUS LI-RADS is effective but can be improved by merging LR-4 and 5 to diagnose HCC and by splitting LR-3 into two subgroups to differentiate iso-iso nodules from other patterns.

Resveratrol corrects aberrant splicing of RYR1 pre-mRNA and Ca2+ signal in myotonic dystrophy type 1 myotubes

Myotonic dystrophy type 1(DM1) is a spliceopathy related to the mis-splicing of several genes caused by sequestration of nuclear transcriptional RNA-binding factors from non-coding CUG repeats of DMPK pre-mRNAs. Dysregulation of ryanodine receptor 1(RYR1), sarcoplasmatic/endoplasmatic Ca^2+-ATPase(SERCA) and α1 S subunit of voltage-gated Ca^2+ channels(Cav1.1) is related to Ca^2+ homeostasis and excitation-contraction coupling impairment. Though no pharmacological treatment for DM1 exists, aberrant splicing correction represents one major therapeutic target for this disease. Resveratrol(RES, 3,5,4′-trihydroxy-trans-stilbene) is a promising pharmacological tools for DM1 treatment for its ability to directly bind the DNA and RNA influencing gene expression and alternative splicing. Herein, we analyzed the therapeutic effects of RES in DM1 myotubes in a pilot study including cultured myotubes from two DM1 patients and two healthy controls. Our results indicated that RES treatment corrected the aberrant splicing of RYR1, and this event appeared associated with restoring of depolarization-induced Ca^2+ release from RYR1 dependent on the electro-mechanical coupling between RYR1 and Cav1.1. Interestingly, immunoblotting studies showed that RES treatment was associated with a reduction in the levels of CUGBP Elav-like family member 1, while RYR1, Cav1.1 and SERCA1 protein levels were unchanged. Finally, RES treatment did not induce any major changes either in the amount of ribonuclear foci or sequestration of muscleblind-like splicing regulator 1. Overall, the results of this pilot study would support RES as an attractive compound for future clinical trials in DM1. Ethical approval was obtained from the Ethical Committee of IRCCS Fondazione Policlinico Universitario A. Gemelli, Rome, Italy(rs9879/14) on May 20, 2014.

Phase Ⅱ study of apatinib in combination with oral vinorelbine in heavily pretreated HER2-negative metastatic breast cancer and clinical implications of monitoring ctDNA

Objective:Apatinib is an oral TKI targeting VEGFR-2.Single-agent apatinib treatment has been shown to produce an objective response in patients with pretreated m BC.Oral vinorelbine also holds promise as a treatment of choice in patients with m BC.This study aimed to investigate the efficacy and safety of the oral vinorelbine-apatinib combination in patients with pretreated m BC.In addition,we detected gene variants in ct DNA to explore the therapeutic implications.Methods:This study enrolled patients with HER2-negative m BC who were pretreated with anthracycline/taxanes.Patients were treated with apatinib at 500 mg/425 mg daily plus oral vinorelbine 60 mg/m2 on days 1,8,and 15 of every cycle(3 weeks).The primary endpoint was PFS.The secondary endpoints were ORR,CBR,OS,and safety.Patients eligible for ct DNA detection were evaluated before and during treatment.Results:Forty patients were enrolled.The median PFS was 5.2 months(95%CI,3.4–7.0 months),and the median OS was 17.4 months(95%CI,8.0–27.0 months).The ORR was 17.1%(6/35),and the CBR was 45.7%(16/35).The most common AEs included gastrointestinal reaction,myelosuppression,and hypertension.In 20 patients,ct DNA was detected at baseline and during treatment.A significant difference was found in PFS for undetected vs.detected baseline ct DNA(13.9 months vs.3.6 months,P=0.018).Conclusions:All-oral therapy with apatinib plus vinorelbine displayed objective efficacy in patients with heavily pretreated HER2-negative m BC,with acceptable and manageable toxicity profiles.Patients with no gene variant detected and lower variant allele frequencies in ct DNA at baseline showed longer PFS.

Impact of COVID-19 in individuals with and without pre-existent digestive disorders with a particular focus on elderly patients

Coronavirus disease 2019(COVID-19)has several extrapulmonary symptoms.Gastrointestinal(GI)symptoms are among the most frequent clinical manifestations of COVID-19,with severe consequences reported in elderly patients.Furthermore,the impact of COVID-19 on patients with pre-existing digestive diseases still needs to be fully elucidated,particularly in the older population.This review aimed to investigate the impact of COVID-19 on the GI tract,liver,and pancreas in individuals with and without previous digestive diseases,with a particular focus on the elderly,highlighting the distinctive characteristics observed in this population.Finally,the effectiveness and adverse events of the anti-COVID-19 vaccination in patients with digestive disorders and the peculiarities found in the elderly are discussed.

Why do we not reverse the path?Stress can cause depression,reduction of brain-derived neurotrophic factor and increased inflammation

The aim of this paper is to describe the direction of the link between stress,depression,increased inflammation and brain-derived neurotrophic factor(BDNF)reduction.We hypothesize that severe stress or prolonged stress can be the driving factor that promote the onset of depression.Both stress and depression,if not resolved over time,activate the production of transcription factors that will switch on pro-inflammatory genes and translate them into cytokines.This cascade fosters systemic chronic inflammation and reduced plasma BDNF levels.Since people with depression have a 60%increased risk of developing type 2diabetes(T2D)and show high levels of inflammation and low levels of BDNF,we hypothesize possible reasons that might explain why T2D,depression and dementia are often associated in the same patient.

Intranasal nerve growth factor for prevention and recovery of the outcomes of traumatic brain injury

Traumatic brain injury is one of the main causes of mortality and disability worldwide.Traumatic brain injury is characterized by a primary injury directly induced by the impact,which progresses into a secondary injury that leads to cellular and metabolic damages,starting in the first few hours and days after primary mechanical injury.To date,traumatic brain injury is not targetable by therapies aimed at preventing and/or limiting the outcomes of secondary damage but only by palliative therapies.Nerve growth factor is a neurotrophin targeting neuronal and non-neuronal cells,potentially useful in preventing/limiting the outcomes of secondary damage in traumatic brain injury.This potential has further increased in the last two decades since the possibility of reaching neurotrophin targets in the brain through its intranasal delivery has been exploited.Indeed,molecules intranasally delivered to the brain parenchyma may easily bypass the blood-brain barrier and reach their therapeutic targets in the brain,with favorable kinetics,dynamics,and safety profile.In the first part of this review,we aimed to report the traumatic brain injury-induced dysfunctional mechanisms that may benefit from nerve growth factor treatment.In the second part,we then exposed the experimental evidence relating to the action of nerve growth factor(both in vitro and in vivo,after administration routes other than intranasal)on some of these mechanisms.In the last part of the work,we,therefore,discussed the few manuscripts that analyze the effects of treatment with nerve growth factor,intranasally delivered to the brain parenchyma,on the outcomes of traumatic brain injury.

Allergy in total knee replacement surgery:Is it a real problem?

Total knee arthroplasty is a common procedure, with extremely good clinical results. Despite this success, it produces 20% unsatisfactory results. Among the causes of these failures is metal hypersensitivity. Metal sensitization is higher in patients with a knee arthroplasty than in the general population and is even higher in patients undergoing revision surgery. However, a clear correlation between metal sensitization and symptomatic knee after surgery has not been ascertained. Surely, patients with a clear history of metal allergy must be carefully examined through dermatological and laboratory testing before surgery. There is no globally accepted diagnostic algorithm or laboratory test to diagnose metal hypersensitivity or metal reactions. The patch test is the most common test to determine metal hypersensitivity, though presenting some limitations. Several laboratory assays have been developed, with a higher sensitivity compared to patch testing, yet their clinical availability is not widespread, due to high costs and technical complexity. Symptoms of a reaction to metal implants present across a wide spectrum, ranging from pain and cutaneous dermatitis to aseptic loosening of the arthroplasty. However, although cutaneous and systemic hypersensitivity reactions to metals have arisen, thereby increasing concern after joint arthroplasties, allergies against implant materials remain quite rare and not a well-known problem. The aim of the following paper is to provide an overview on diagnosis and management of metal hypersensitivity in patients who undergo a total knee arthroplasty in order clarify its real importance.

Dynamic contrast enhanced ultrasound in gastrointestinal diseases:A current trend or an indispensable tool?

Contrast enhanced ultrasound(CEUS)has been widely implemented in clinical practice because of the enormous quantity of information it provides,along with its low cost,reproducibility,minimal invasiveness,and safety of the secondgeneration ultrasound contrast agents.To overcome the limitation of CEUS given by the subjective evaluation of the contrast enhancement behaviour,quantitative analysis of contrast kinetics with generation of time-intensity curves has been introduced in recent years.The quantification of perfusion parameters[named as dynamic-CEUS(D-CEUS)]has several applications in gastrointestinal neoplastic and inflammatory disorders.However,the limited availability of large studies and the heterogeneity of the technologies employed have precluded the standardisation of D-CEUS,which potentially represents a valuable tool for clinical practice in management of gastrointestinal diseases.In this article,we reviewed the evidence exploring the application of D-CEUS in gastrointestinal diseases,with a special focus on liver,pancreas,and inflammatory bowel diseases.

Special features of SARS-CoV-2 in daily practice

The severe acute respiratory syndrome-coronavirus-2(commonly known as SARS-CoV-2)is a novel coronavirus(designated as 2019-nCoV),which was isolated for the first time after the Chinese health authorities reported a cluster of pneumonia cases in Wuhan,China in December 2019.Optimal management of the Coronavirus Disease-2019 disease is evolving quickly and treatment guidelines,based on scientific evidence and experts’opinions with clinical experience,are constantly being updated.On January 30,2020,the World Health Organization declared the SARS-CoV-2 outbreak as a"Public Health Emergency of International Concern".The total lack of immune protection brought about a severe spread of the contagion all over the world.For this reason,diagnostic tools,patient management and therapeutic approaches have been tested along the way,in the desperate race to break free from the widespread infection and its fatal respiratory complications.Current medical knowledge and research on severe and critical patients’management and experimental treatments are still evolving,but several protocols on minimizing risk of infection among the general population,patients and healthcare workers have been approved and diffused by International Health Authorities.

Endoscopic ultrasound-guided gallbladder drainage in pancreatic cancer and cholangitis: A case report

BACKGROUND Head pancreatic cancers often present with clinical challenges requiring biliary drainage for chemotherapy or palliative scope.If usual endoscopic modalities fail or if percutaneous approach is not feasible,endoscopic ultrasound(EUS)guided biliary drainage can be considered.Here we describe and discuss an interesting clinical case in which EUS-guided gallbladder drainage(EUS-GBD)was chosen to treat acute severe cholangitis in a patient with advanced pancreatic cancer.CASE SUMMARY An 84-year-old female with a previous EUS-biopsy proven diagnosis of head pancreatic cancer presented with clinical signs of acute cholangitis.In September 2018 she had positioned a biliary and duodenal stent to relieve jaundice and an initial duodenal substenosis.In the emergency ward,an abdominal computed tomography scan showed proximal biliary stent occlusion due to neoplastic progression,but endoscopic retrograde cholangiopancreatography was impossible because of worsening duodenal stenosis and the absence of a chance to reach the Vater’s papilla area.EUS-guided choledocoduodenostomy was not technically feasible but because the cystic duct was free of neoplastic infiltration,an EUS-GBD using an Axios^TM stent was successfully performed.The patient started to feed after 48 h and was discharged 1 wk later.No other hospitalizations due to cholangitis or symptoms of Axios^TM stent occlusion/dysfunction were observed up until her death 6 mo later due to underlying disease.CONCLUSION This case demonstrated how different EUS therapeutic approaches could have a key role to treat critical and seemingly unsolvable situations and that they could play a more fundamental role in the next future.

Arteriovenous malformations:the newest Sonic hedgehog game in the postnatal brain

The morphogen Sonic hedgehog(Shh)is crucial for the embryonic development of the central nervous system,but is also an important player in the postnatal brain,with activities that range from the modulation of self-renewal and specification of neural stem cells to the regulation of neural regeneration after injury.Active Shh signaling occurs also in molecular subclasses of brain tumors,such as medulloblastoma and adult glioma.

Alcohol use disorder and liver injury related to the COVID-19 pandemic

Alcohol use disorder is a complex and heterogeneous phenomenon that can be studied from several points of view by focusing on its different components.Alcohol is a hepatotoxin whose metabolism creates profound alterations within the hepatocyte.The liver is the central organ in the metabolism of alcohol,a process that also involves other organs and tissues such as the brain,heart and muscles,but the most relevant organ is the liver.The anatomopathological alterations in the liver associated with the prolonged use of alcohol range from the simple accumulation of neutral fats in the hepatocytes,to cirrhosis and hepatocellular carcinoma.Alcohol abuse frequently leads to liver disease such as steatosis,steatohepatitis,fibrosis,cirrhosis,and tumors.Following the spread of coronavirus disease 2019(COVID-19),there was an increase in alcohol consumption,probably linked to the months of lockdown and smart working.It is known that social isolation leads to a considerable increase in stress,and it is also recognized that high levels of stress can result in an increase in alcohol intake.Cirrhotic patients or subjects with liver cancer are immunocompromised,so they may be more exposed to COVID-19 infection with a worse prognosis.This review focuses on the fact that the COVID-19 pandemic has made the emergence of alcohol-induced liver damage a major medical and social problem.

Limb lengthening with PRECICE magnetic nail in pediatric patients: A systematic review

BACKGROUND Limb lengthening techniques play an increasingly important role in the pediatric orthopedic field.The principles of the osteogenesis distraction bonded traditionally with external fixators;however,the recent deployment of fully implantable systems has been able to overcome severities related to external fixators.The PRECICE®is an implantable limb lengthening intramedullary nail system that is remotely controlled and magnetically driven.AIM To review the current literature available on this matter in order to assess the PRECICE clinical and radiological outcomes and its possible complications in a population of pediatric patients undergoing limb lengthening.METHODS Only five studies met the inclusion criteria and were consequently included in the review for a total of 131 patients and 135 femurs.The clinical and radiological outcomes of interest were:the main lengthening obtained,the distraction rate,the period of time to full weight bearing,the consolidation index,and the Association for the Study and Application of Methods of Ilizarov score.RESULTS In conclusion,data collected from the articles under investigation were comparable with the exception of the consolidation index.Unfortunately,the study population was too small and the patients’follow-up was too short to make definitive conclusions.CONCLUSION This review shows that the PRECICE Nail System is still a therapeutic challenge in limb lengthening for pediatric orthopedic surgeons;however,careful preoperative planning and an accurate surgical technique could allow the correction of more complex deformities with a low rate of complications.

Pulmonary Perfusion Asymmetry in Patients after Repair of Tetralogy of Fallot: A 4D Flow MRI-Based Study

Background:Repaired Tetralogy of Fallot(rTOF)patients may have residual lesions such as main(MPA)and branch pulmonary artery stenosis(BPAS).While MPA stenosis is well studied,few data are available on BPAS in rTOF.We aimed to describe pulmonary perfusion in a large paediatric cohort of rTOF and its impact on right ventricular and outflow-tract hemodynamics using 4D flow CMR.Methods:130 consecutive patients(mean age at CMR 14.3±4.6 years)were retrospectively reviewed.96 patients had transannular patch without valve preservation while 34 patients had conserved annulus or valved conduit.A pulmonary blood flow ratio(right pulmonary artery(RPA)/left pulmonary artery(LPA))between 0.75 and 1.56 was considered normal.Results:Asymmetric pulmonary perfusion was present in 59/130 patients(45%),with 54/59(91%)having left lung hypoperfusion(blood flow ratio>1.56).RPA/LPA perfusion ratio in the whole cohort was independently associated with the LPA Z-score(−0.053,p=0.007),the RPA regurgitant fraction(RF)(0.013,p=0.011)and previous LPA stenting(0.648,p=0.004).Decreasing LPA%perfusion(and conversely increasing RPA%perfusion)was significantly associated with higher MPA diameter Z-score(−0.06,p=0.007).On multivariate analysis,MPA Z-score was independently associated with pulmonary RF(0.48,p<0.001)and with right ventricular indexed volumes(coefficient 3.6,p=0.023).In patients with transannular patch repair,asymmetric pulmonary flow was an independent predictor of right ventricular ejection fraction(RVEF)(−3.66,p=0.04).Conclusions:Pulmonary perfusion asymmetry is frequent in rTOF and is associated with abnormal right ventricular and outflow-tract hemodynamics,including MPA dilatation and decreased RVEF in patients after transannular patch.