Advancing our understanding of monocyte HLA-DR,S100A9,and the potential for individualized therapies in sepsis

By def inition, sepsis refers to a life threatening organ dysfunction due to a dysregulated host response to an infection[1]. More precisely, sepsis triggers a multifaceted response characterized by a simultaneous manifestation of proinflammatory and anti-inflammatory elements that disrupt mechanisms intended to maintain homeostasis. Initially, an overwhelming hyperinflammatory reaction ensues, resulting in tissue damage and organ dysfunction.

Refractory intraocular hypertension after dexamethasone-implant intravitreal injection treated with Preserflo MicroShunt implantation

Dear Editor,Herein,we report a case of a patient who presented with refractory ocular hypertension(OHT)after a dexamethasone implant(DEX-I)injection.Intraocular pressure(IOP)was finally managed after Preserflo Micro Shunt implantation,allowing the continued use of dexamethasone implant.

Current strategies for the restoration of adequate lordosis during lumbar fusion

Not restoring the adequate lumbar lordosis during lumbar fusion surgery may result in mechanical low back pain, sagittal unbalance and adjacent segment degeneration. The objective of this work is to describe the current strategies and concepts for restoration of adequate lordosis during fusion surgery. Theoretical lordosis can be evaluated from the measurement of the pelvic incidence and from the analysis of spatial organization of the lumbar spine with 2/3 of the lordosis given by the L4-S1 segment and 85% by the L3-S1 segment. Technical aspects involve patient positioningon the operating table, release maneuvers, type of instrumentation used(rod, screw-rod connection, interbody cages), surgical sequence and the overall surgical strategy. Spinal osteotomies may be required in case of fixed kyphotic spine. AP combined surgery is particularly efficient in restoring lordosis at L5-S1 level and should be recommended. Finally, not one but several strategies may be used to achieve the need for restoration of adequate lordosis during fusion surgery.

Locoregional therapies and their effects on the tumoral microenvironment of pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma(PDAC) is expected to become the second leading cause of death from cancer by 2030. Despite intensive research in the field of therapeutics, the 5-year overall survival is approximately 8%, with only 20% of patients eligible for surgery at the time of diagnosis. The tumoral microenvironment(TME) of the PDAC is one of the main causes for resistance to antitumoral treatments due to the presence of tumor vasculature, stroma, and a modified immune response. The TME of PDAC is characterized by high stiffness due to fibrosis, with hypo microvascular perfusion, along with an immunosuppressive environment that constitutes a barrier to effective antitumoral treatment. While systemic therapies often produce severe side effects that can alter patients’ quality of life, locoregional therapies have gained attention since their action is localized to the pancreas and can thus alleviate some of the barriers to effective antitumoral treatment due to their physical effects. Local hyperthermia using radiofrequency ablation and radiation therapy-most commonly using a local high single dose-are the two main modalities holding promise for clinical efficacy. Recently, irreversible electroporation and focused ultrasound-derived cavitation have gained increasing attention. To date, most of the data are limited to preclinical studies, but ongoing clinical trials may help better define the role of these locoregional therapies in the management of PDAC patients.

Neuronal networks in mental diseases and neuropathic pain:Beyond brain derived neurotrophic factor and collapsin response mediator proteins

The brain is a complex network system that has the capacity to support emotion, thought, action, learning and memory, and is characterized by constant activity, constant structural remodeling, and constant attempt to compensate for this remodeling. The basic insight that emerges from complex network organization is that substantively different networks can share common key organizational principles. Moreover, the interdependence of network organization and behavior has been successfully demonstrated for several specific tasks. From this viewpoint, increasing experimental/clinical observations suggest that mental disorders are neural network disorders. On one hand, single psychiatric disorders arise from multiple, multifactorial molecular and cellular structural/functional alterations spreading throughout local/global circuits leading to multifaceted and heterogeneous clinical symptoms. On the other hand, various mental diseases may share functional deficits across the same neural circuit as reflected in the overlap of symptoms throughout clinical diagnoses. An integrated framework including experimental measures and clinical observations will be necessary to formulate a coherent and comprehensive understanding of how neural connectivity mediates and constraints the phenotypic expression of psychiatric disorders.

Dual antibiotic loaded bone cement in patients at high infection risks in arthroplasty: Rationale of use for prophylaxis and scientific evidence

In view of the demographic changes and projected increase of arthroplasty procedures worldwide,the number of prosthetic joint infection cases will naturally grow.Therefore,in order to counteract this trend more rigid rules and a stricter implementation of effective preventive strategies is of highest importance.In the absence of a"miracle weapon"priorities should lie in evidence-based measures including preoperative optimization of patients at higher infection risks,the fulfilment of strict hygiene rules in the operating theatre and an effective antibiotic prophylaxis regimen.Instead of a"one size fits all"philosophy,it has been proposed to adjust the antibiotic prophylaxis protocol to major infection risks taking into account important patient-and procedure-related risk factors.A stronger focus on the local application mode via use of high dose dual antibioticloaded bone cement in such risk situations may have its advantages and is easy to apply in the theatre.The more potent antimicrobial growth inhibition in vitro and the strong reduction of the prosthetic joint infection rate in risk for infection patients with aid of dual antibiotic-loaded bone cement in clinical studies align with this hypothesis.

Double cholecystectomy in case of accessory gallbladder:Not as easy as two cholecystectomies

To the Editor:Accessory gallbladders(AG)are rare and their management are usually challenging.These variations are related with an abnormal division of the bile ducts precursors between the 5th and the 12th week of pregnancy.Harlaftis et al.[1]proposed an anatomical classification of these variations based on the embryologic abnormalities described.In type 1 both gallbladders are connected to the common bile duct at the same location.In type 2 the AG can reach either the common bile duct(ductular type)or an intrahepatic biliary duct(trabecular type).In type 3,three gallbladders are present.

Does the Animal Origin Influence the Calcification of Xenograft Tissue Heart Valve Substitutes? Comparison between Bovine and Camel Pericardium in a Subcutaneous Rat Model

Objective: To validate the hypothesis that camel pericardium could be more protected than bovine pericardium against calcification process according to the huge difference in their respective lifestyle and lifetime. Methods: Glutaraldehyde (GA) fixed bovine and camel pericardium samples (BP and CP respectively) were both implanted in 30 New Zealand white rats (2 BP and 2 CP matched specimens in each animal) and explanted after 60 days. Unimplanted GA-fixed samples of both species served as control. Matched implanted samples and unimplanted samples were randomly submitted to elemental analysis by spectroscopy, phospholipid extraction, macroscopic and X-ray examination and histology. Results: At 60 days, calcium and phosphorus content were respectively 9.54% ± 3.1% and 4.79% ± 1.4% of tissue dry weight in BP, and 12.52% ± 2.7% and 6.14% ± 1.3% of tissue dry weight in CP (ns). In X-ray analysis, the calcification score was 1.28 ± 0.45 and 2.14 ± 0.98 in BP and CP samples respectively without significant difference (p < 0.08). In histology, calcifications were lower in BP than in CP: 1.37 ± 0.85 vs 2.28 ± 0.83 (ns);collagen fibers were better conserved in BP than in CP: 2.4 ± 0.48 vs 1.87 ± 0.78 (ns), and less disoriented: 25% vs 62% (ns). In unimplanted samples, there was a higher but not significant rate of extracted lipids in CP: 5.7 ± 1.8 vs 9.5 ± 3.8 nanomoles in PS fraction and 11.3 ± 3.7 vs 19 ± 7.7 nanomoles in total fatty acids, in BP and CP samples respectively. All results were in conjunction and demonstrated a higher but not significant rate of mineralization in camel pericardium after implantation, which could be related to a higher but not significant basic rate of phospholipid and fatty acids. Conclusion: This experiment study in a subcutaneous rat model has failed to valid our hypothesis. Because the differences observed between bovine and camel pericardium did not reach the significance, at the best, there is no difference between both species and at the worst, camel pericardium has a higher rate of the phosphatidylserine fraction of phospholipid, and is more sensitive and prompt to calcification.

Optimization of Maturation of Radio-Cephalic Arteriovenous Fistula Using a Model Relating Energy Loss Rate and Vascular Geometric Parameters

The main reason for the early failure of radio-cephalic arteriovenous fistula (RCAVF) is non-maturity, which means that the blood flow rate in the fistula cannot increase to the expected value for dialysis. From a mechanical perspective, the vascular resistance at the artificially designed anastomosis causes an energy loss that affects blood flow rate growth and leads to early failure. This research studied how to maximize the RCAVF maturity and primary patency by controlling the energy loss rate. We theoretically analyzed and derived a model that evaluates the energy loss rate Eavf in RCAVF as a function of its blood vessel geometric parameters (GPs) for given flow rates. There was an aggregate of five controllable GPs in RCAVF: radial artery diameter (Dra), cephalic vein diameter (Dcv), blood vessel distance between artery and vein (h), anastomotic diameter (Da), and anastomotic angle (θ). Through this analysis, it was found that Eavf was inversely proportional to Dra, Dcv, Da, and θ, whereas proportional to h. Therefore, we recommended surgeons choose the vessels with large diameters, close distance, and increase the diameter and angle of the anastomosis to decrease the early failure of RCAVF. Simultaneously, we could explain the results of many clinical empiricisms with our formula. We found that increasing Dcv and θ was more significant in reducing Eavf than increasing Dra and Da. Based on our model, we could define two critical energy loss rates (CELa, CELb) to help surgeons evaluate the blood vessels and choose the ideal range of θ, and help them design the preoperative RCAVF plan for each patient to increase the maturity and the primary patency of RCAVF.

Prevalence of iron deficiency in patients aged 75 years or older with heart failure

Background The latest studies presented at the American Heart Association (AHA) meeting on heart failure and the update of the European Cardiology Society’s (ECS) recommendations on heart failure in 2016 recommend intravenous iron supplementation in patients with heart failure, reduced ejection fraction and iron deficiency for improves walking performance and quality of life, and reduces morbidity. In the present study, we investigated the prevalence of iron deficiency in heart failure patients aged 75 years or older, as there is currently no data on these patients. Methods We performed an observational study on hospitalized patients in Geriatric Cardiology Department. Among the 462 patients hospitalized during eight months, 176 were eligible for inclusion;22 patients was significant interference with an inflammatory syndrome (high ferritin with high C-reactive protein), and for 13 patients iron-related data were not available. For each patient included, a complete iron assessment and type of heart failure was available. Results A total of 141 patients were included, the mean age was 88 years (range: 75–101), and there were 52 (36.9%) of patients with reduced ejection fraction (EF), 37 (26.2%) with mid-range EF, and 52 (36.9%) with preserved EF. Irrespective of heart failure type, 73.8% had iron deficiency (95% CI: 65.7%–80.8%);this was found in 57.7%(95% CI: 43.2%–71.3%) of those with reduced EF, 78.4%(95% CI: 61.8%–90.2%) of those with mid-range EF, and 86.5%(95% CI: 74.2%–94.4%) of those with preserved EF (P = 0.003). Conclusion The prevalence of iron deficiency was very high in very elderly patients with heart failure, especially those with HF with mid-range EF or HF with preserved EF.

Factors associated with DAA virological treatment failure and resistance-associated substitutions description in HIV/HCV coinfected patients

AIM To describe factors associated with treatment failure and frequency of resistance-associated substitutions(RAS).METHODS Human immunodeficiency virus(HIV)/hepatitis C virus(HCV) coinfected patients starting a first direct-acting antiviral(DAA) regimen before February 2016 and included in the French ANRS CO13 HEPAVIH cohort were eligible. Failure was defined as:(1) non-response [HCV-RNA remained detectable during treatment, at end of treatment(EOT)]; and(2) relapse(HCVRNA suppressed at EOT but detectable thereafter). Sequencing analysis was performed to describe prevalence of drug class-specific RAS. Factors associated with failure were determined using logistic regression models.RESULTS Among 559 patients, 77% had suppressed plasma HIV-RNA < 50 copies/mL at DAA treatment initiation, 41% were cirrhotic, and 68% were HCV treatmentexperienced. Virological treatment failures occurred in 22 patients and were mainly relapses(17, 77%) then undefined failures(3, 14%) and non-responses(2, 9%). Mean treatment duration was 16 wk overall. Posttreatment NS3, NS5 A or NS5 B RAS were detected in 10/14 patients with samples available for sequencing analysis. After adjustment for age, sex, ribavirin use, HCV genotype and treatment duration, low platelet count was the only factor significantly associated with a higher risk of failure(OR: 6.5; 95%CI: 1.8-22.6). CONCLUSION Only 3.9% HIV-HCV coinfected patients failed DAA regimens and RAS were found in 70% of those failing. Low platelet count was independently associated with virological failure.

Biomarkers and atrial fibrillation: A new paradigm for assessing the progression of left atrial endocardial remodelling

Atrial fibrillation is a heterogeneous disorder that is usually characterized by paroxysmal onset, particularly in patients without structural heart disease. Defining biological markers of atrial remodelling would help identify patients at high risk who would benefit most from prophylactic treatment and careful monitoring. Biomarkers of atrial fibrillation progression would be helpful for following patients that present with asymptomatic atrial fibrillation. Notably, the roles of such markers in the pathophysiology of atrial fibrillation must be determined. Some markers may indicate the presence, complications or progression of the disease, while others may be involved in key pathological processes and thus represent novel therapeutic targets. Although a number of markers have been reported as potential predictors of paroxysmal atrial fibrillation progression towards persistent arrhythmia, their usefulness and clinical value need further validation. This report reviews several newly identified markers of atrial fibrillation progression.

Involvement of glycated albumin in adipose-derived-stem cellmediated interleukin 17 secreting T helper cell activation

BACKGROUND Advanced glycation end products(AGE)are a marker of various diseases including diabetes,in which they participate to vascular damages such as retinopathy,nephropathy and coronaropathy.Besides those vascular complications,AGE are involved in altered metabolism in many tissues,including adipose tissue(AT)where they contribute to reduced glucose uptake and attenuation of insulin sensitivity.AGE are known to contribute to type 1 diabetes(T1D)through promotion of interleukin(IL)-17 secreting T helper(Th17)cells.AIM To investigate whether lean adipose-derived stem cells(ASC)could be able to induce IL-17A secretion,with the help of AGE.METHODS As we have recently demonstrated that ASC are involved in Th17 cell promotion when they are harvested from obese AT,we used the same co-culture model to measure the impact of glycated human serum albumin(G-HSA)on human lean ASC interacting with blood mononuclear cells.IL-17A and pro-inflammatory cytokine secretion were measured by ELISA.Receptor of AGE(RAGE)together with intercellular adhesion molecule 1(ICAM-1),human leukocyte Antigen(HLA)-DR,cluster of differentiation(CD)41,and CD62P surface expressions were measured by cytofluorometry.Anti-RAGE specific monoclonal antibody was added to co-cultures in order to evaluate the role of RAGE in IL-17A production.RESULTS Results showed that whereas 1%G-HSA only weakly potentiated the production of IL-17A by T cells interacting with ASC harvested from obese subjects,it markedly increased IL-17A,but also interferon gamma and tumor necrosis factor alpha production in the presence of ASC harvested from lean individuals.This was associated with increased expression of RAGE and HLA-DR molecule by cocultured cells.Moreover,RAGE blockade experiments demonstrated RAGE specific involvement in lean ASC-mediated Th-17 cell activation.Finally,platelet aggregation and ICAM-1,which are known to be induced by AGE,were not involved in these processes.CONCLUSION Thus,our results demonstrated that G-HSA potentiated lean ASC-mediated IL-17A production in AT,suggesting a new mechanism by which AGE could contribute to T1D pathophysiology.

Differences in oxidative stress dependence between gastric adenocarcinoma subtypes

瞄准：在与他们的病理学的标准和组织学的子类型的关系在 pre 肿瘤、肿瘤的胃粘膜调查氧化应力的程度。方法：从 98 个病人的 104 胃的腺癌的一个总数(88 渗透性并且 16 个 intraepithelial 肿瘤)为 i NOS 的表示和包含包含 DNA ，，的蛋白质和 8-hydroxy-2'-deoxyguanosine ( 8-OH-dG )的 nitrotyrosine ( NTYR )的出现组织化学地是估计的免疫到蛋白质和 DNA 的没有生产和损坏的标记。结果：为 i NOS， NTYR 和 8-OH-dG 染色的肿瘤房间分别地在 41% 渗透性的癌， 62% 和 50% 被检测。三个标记在 intraepithelial 癌第一次被显示出。i NOS 的表示是显著地在与弥漫的癌(DC ) 相比的管状的癌(TC ) 更经常(54% 对 18% ；P = 0.008 ) 或在多形的癌(PolyC )(54% 对 21% ；P = 0.04 ) 。染色的 NTYR 更经常显然在 PolyC 比那在 TC 被发现(72% 对 30% ；P = 0.03 ) 。向当远转移(下午) 是在场的时，染色的 i NOS 的更高的率有一个趋势。在渗透性的 TC，氧化压力标记的存在显著地没与组织学的等级，发炎的密度，渗入(磅) 的深度，淋巴节点传播(pN ) 和病理学的阶段(pTNM ) 被相关。结论：iNOS 氧化的小径可以在 TC 起一个重要作用，但是中等在 PolyC 和 DC。DNA 氧化和蛋白质硝代发生在三种子类型。基于 NTYR 层次， TC 和 PolyC 的有效差量作为二种不同子类型出现。

Polymorphic multiple hepatocellular adenoma including a non-steatotic HNF1α-inactivated variant

To the Editor:Hepatocellular adenomas(HCAs)consist of benign liver tumors favored by the use of oral contraceptives,which preferentially occur in women.[1,2]They expose to the risk of hemorrhage(20%of cases)and more rarely,to the risk of malignant transformation(4%-10%of cases).[3,4]Multiple HCAs,which are defined by the presence of 10 or more

Five-year outcomes with anti-vascular endothelial growth factor in neovascular age-related macular degeneration:results of the Comparison of Age-related Macular Degeneration Treatments Trials

Age-related macular degeneration(AMD)is the leading cause of irreversible blindness in the elderly in industrialized countries(1,2).Current treatments for AMD are severely limited and only the wet form can be treated with anti-vascular endothelial growth factor(anti-VEGF).Although anti-VEGF is a palliative treatment,this drug dramatically improves the prognosis for patients with this disease(3).For example,in a population-based study in Denmark,the incidence of legal blindness from AMD was reduced by 50%after 2006(4).

Heidenhain型克-雅病

Introduction.Creutzfeldt-Jakob’s disease has various anatomoclinical present ations including a rare form with preponderant visual signs described by Heidenh ain. In this form, the visual symptoms may be isolated for a few weeks, leading to multiple ophthalmological examinations. Observation. We report the case of a 75-year-old woman who developed isolated visual disorders which rapidly increa sed over a period of two months. Addition of neurological symptoms, abnormalitie s of EEG and positivity of 14-3-3 protein led to the diagnosis of Creutzfeldt -Jakob’s disease. The patient died 14 months after the first neuroophthalmolog ic signs. The diagnosis was established by post-mortem examination and immuno- electrophoretic demonstration of type 1 prion protein. Conclusion. Heidenhain’s form of Creut zfeldt Jakob’s disease highlights the importance of general rules for preventio n of iatrogenic hazard during ophthalmological examinations.

Multiple evanescent white dot syndrome relapse following BNT162b2 mRNA COVID-19 vaccination

Dear Editor,We report a case of multiple evanescent white dot syndrome(MEWDS)relapse following mRNA corona virus disease 2019(COVID-19)vaccination.MEWDS is a choroidal inflammatory disease belonging to the group of“white dot syndromes”group,with an excellent prognosis[1].MEWDS is usually idiopathic,but there have been reports of MEWDS following viral infection or vaccination[1-2].

Cytoreductive surgery and hyperthermic intraperitonealchemotherapy in gastric cancer

Gastric cancer associated peritoneal carcinomatosis(GCPC) has a poor prognosis with a median survival of less than one year. Systemic chemotherapy including targeted agents has not been found to significantly increase the survival in GCPC. Since recurrent gastric cancer remains confined to the abdominal cavity in many patients, regional therapies like aggressive cytoreductive surgery( CRS) and hyperthermic intraperitoneal chemotherapy(HIPEC) have been investigated for GCPC. HIPEC has been used for three indications in GC- as an adjuvant therapy after a curative surgery, HIPEC has been shown to improve survival and reduce peritoneal recurrences in many randomised trials in Asian countries; as a definitive treatment in established PC, HIPEC along with CRS is the only therapeutic modality that has resulted in longterm survival in select groups of patients; as a palliative treatment in advanced PC with intractable ascites, HIPEC has been shown to control ascites and reduce the need for frequent paracentesis. While the results of randomised trials of adjuvant HIPEC from western centres are awaited, the role of HIPEC in the treatment of GCPC is still evolving and needs larger studies before it is accepted as a standard of care.

Evaluation of renal function in patients with cirrhosis:Where are we now?

In the clinical context of the patients with liver cirrhosis,accurate evaluation of the renal function is potentially crucial.Indeed,it can lead to early diagnosis of both acute kidney injury and chronic kidney disease and to reliable characterization of the renal status of the patient before performing a liver transplantation.Despite some limitations,the assay of serum creatinine(SCr)is universally used to estimate glomerular filtration rate(GFR)because of its wide availability,its simplicity and because it is inexpensive.Nevertheless,several reports show that the value of this assay to estimate GFR is strongly challenged in cirrhotic patients,especially in patients with liver failure and/or severely impaired renal function.This has led to seek new alternatives to estimate more reliably the GFR in these patients.Although the reference methods,based on the utilization of exogenous markers,allow measuring GFR and thereby constitute the"gold standard"to evaluate renal function,they are not feasible in routine clinical practice.Several studies have shown that a cystatin C(CysC)based formula perform better than the SCr-based estimates in cirrhotic patients and the estimation of GFR by these formulas could therefore lead to optimize the management of the patients.A new estimate based on CysC has been recently developed using a large number of patients and the first results regarding the evaluation of its performance are promising,making this new formula the best candidate for a reference estimate of the renal function in cirrhotic patients.