Evaluation of computed tomography obstruction index in guiding therapeutic decisions and monitoring percutanous catheter fragmentation in massive pulmonary embolism

In the present study, we evaluated computed tomography pulmonary angiography （CTPA） in guiding therapeutic decisions and monitoring patients undergoing percutaneous catheter fragmentation in acute massive pulmonary embolism. From Jan 2003 to Dec 2009, 35 patients were diagnosed with acute massive pulmonary embolism by CTPA （TO） and treated with percutaneous catheter fragmentation. The severity was assessed by CT obstruction index （Qanadli index） and compared with Miller index. CTPA, oxygen saturation （SaO2） and pulmonary artery pressure were performed as follow-up index. The mean percentage of Qanadli index was （55 ± 13）% （range, 40%- 75%）, and Miller index was （62 ± 15）% （range, 45%-85%）. Correlations between them were statistically significant （r = 0.867, P 〈 0.0001）. The Qanadli index showed significant reduction [TO： （55±13）%; TI： （12±10）%; P 〈 0.001] in 33 patients. Significant correlation was observed between the Qanadli index, SaO2 （r = 0.934）, and pulmonary artery pressure （r = 0.813）. The Qanadli index provides an accurate method for distinguishing massive pulmonary embolism from sub-massive pulmonary embolism. It can be used to determine therapeutic options and monitor clinical outcomes.

Pulmonary Embolism: Epidemiological, Clinical, Therapeutic and Evolution Aspects in the Medicine Department of Hospital of Mali Bamako

Background: Pulmonary embolism (PE) is a severe form of venous thromboembolic disease. In Africa, prevalence of PE in hospitalized medical patients varies among studies. Objective: Aim of this work was to study the epidemiological, clinical, therapeutic and evolution aspects of PE in the medicine department of Mali’s Hospital Bamako-Mali. Methodology: This was a retrospective cross-sectional study carried out from January 01, 2017 to December 31, 2020 in the medicine department of Mali’s hospital Bamako, including all inpatients admitted for PE during the study period. Results: Of 1814 hospitalized patients, 54 patients had pulmonary embolism. Hospital frequency of pulmonary embolism was 2.97%. Predominance was female and sex-ratio M/F was 0.38. Mean age in our series was 54.24 ±1.19 years. Predisposing factors to pulmonary embolism were dominated by obesity 37%, high blood pressure 35.2% and history of cardiovascular disease 20.4%. Dominant signs were dyspnoea and chest pain in 83.3% and 70.4% of cases respectively. Probability of pulmonary embolism was high in 40.7% according to Wells score. Patients with right heart failure were 22.2%. EKG showed sinus tachycardia70.4% and S1Q3 aspect 7.4%. Heart right chambers were dilated at transthoracic echography 42.6%. Obstruction was bilateral at chest angio CT for 51.9% and proximal for 42.6%. Deep venous thrombosis was associated at EP in 16.6%. Treatment was low weight molecular heparin followed by vitamin K antagonist or direct oral anticoagulant. One patient was successfully treated by thrombolysis. Hospital mortality was 16.7%. Conclusion: PE is a serious disease probably underdiagnosed. It is responsible of important mortality.

Epidemio-Clinical, Therapeutic and Evolutive Aspects of Pulmonary Embolism in Young Subject in the Cardiology Department in Point “G” Hospital University Center Bamako

Objective: The purpose of this work was to determine the epidemiological, clinical and evolutionary aspects of the pulmonary embolism of the young person in the cardiology department of the University Hospital Center (CHU) Point G in Bamako-Mali. Methodology: This was an analytical study from January 01, 2018 to December 31, 2018 in the CHU Point G cardiology department, including all patients hospitalized during this period. Results: Of 1379 hospitalized patients, 19 patients were concerned by pulmonary embolism of the young person. The prevalence of pulmonary embolism of the young person was 1.37%. The most affected age group was 21 - 30 (47.4%) of patients. The predominance was female (89.47%) with a gender ratio of 0.11 in favour of women. The average age in the series was 29.79 years with extremes of 16 years and 40 years. Factors predisposing to pulmonary embolism were dominated by peri partum, cardiomyopathy and obesity with 47.3%, 31.57% and 21.1%, respectively. The dominant signs were chest pain and dyspnea in 94.7% and 89.5% of cases respectively. Pulmonary embolism was unlikely in 60.52% according to the Geneva and Wells score simplified. At the thoracic angioscanner, the embolism was bilateral in 52.6% of cases and distal in 36.8% of patients;in 10 patients who performed cardiac ultrasound, pulmonary arterial hypertension (70%), dilation of the right ventricle (20%) and left ventricular dilation (40%). Hyper leucocytosis (47.4%), anemia and low prothrombin rate (TP) (22.2%) were the most found biological abnormalities. More than 2/3 (68.5%) our patients had an intermediate mortality risk according to the PESI (Pulmonary Embolism Severity Index) score. The average hospital stay was 10 days. Hospital mortality was 10.5%. Conclusion: The pulmonary embolism of the young person is a frequent, serious and multifactorial pathology and the female sex is most affected especially during peri partum periods, hence the need for preventive measures. Clinical signs are not specific and based on the assessment of clinical probability. Pulmonary angioscanner remains the confirmation review in our context.

Advances in Zika virus vaccines and therapeutics:A systematic review

Zika virus(ZIKV)is the causative agent of a viral infection that causes neurological complications in newborns and adults worldwide.Its wide transmission route and alarming spread rates are of great concern to the scientific community.Numerous trials have been conducted to develop treatment options for ZIKV infection.This review highlights the latest developments in the fields of vaccinology and pharmaceuticals developments for ZIKV infection.A systematic and comprehensive approach was used to gather relevant and up-to-date data so that inferences could be made about the gaps in therapeutic development.The results indicate that several therapeutic interventions are being tested against ZIKV infection,such as DNA vaccines,subunit vaccines,live-attenuated vaccines,virus-vector-based vaccines,inactivated vaccines,virus-like particles,and mRNA-based vaccines.In addition,approved anti-ZIKV drugs that can reduce the global burden are discussed.Although many vaccine candidates for ZIKV are at different stages of development,none of them have received Food and Drug Authority approval for use up to now.The issue of side effects associated with these drugs in vulnerable newborns and pregnant women is a major obstacle in the therapeutic pathway.

A fast-track diagnostic and therapeutic strategy for acute pulmonary embolism patients at peri-operational period

Acute pulmonary embolism(APE) in operation room is a constant,lethal but treatable disease.A fast determination of APE in an operation room is currently difficult due to a non-specificity on its signs,symptoms,electrocardiograph findings,arterial blood gas abnormalities and chest X-rays.Clinically,an APE can automatically originate from a small and clinically asymptomatic embolus to massive,proximal emboli with shock during a scheduled surgery period.An accurate,brief and prompt diagnostic and therapeutic strategy for APE in a peri-operation period is crucial for anesthesiologists to make a decision on an appropriate clinical intervention to improve patients' outcomes.The purpose of this mini-review article is to illuminate a fast-track diagnostic and therapeutic strategy for APE patients in a perioperative period through a hybrid of the high sensitive and high specific viable diagnostic modality of D-dimer assay in conjunction with necessary emergent pulmonary angiography(EPA),including digital subtraction angiography(DSA),or a spiral computed tomography angiography(sCTA) for APE patients' diagnosis and treatment during operation.The postulated fast-track diagnostic and therapeutic strategy can effectively confirm or exclude highly suspected APE and simultaneously provide fast therapeutic opportunities for APE patients at an operative period.

Dual ligand-targeted Pluronic P123 polymeric micelles enhance the therapeutic effect of breast cancer with bone metastases

Bone metastasis secondary to breast cancer negatively impacts patient quality of life and survival.The treatment of bone metastases is challenging since many anticancer drugs are not effectively delivered to the bone to exert a therapeutic effect.To improve the treatment efficacy,we developed Pluronic P123(P123)-based polymeric micelles dually decorated with alendronate(ALN)and cancer-specific phage protein DMPGTVLP(DP-8)for targeted drug delivery to breast cancer bone metastases.Doxorubicin(DOX)was selected as the anticancer drug and was encapsulated into the hydrophobic core of the micelles with a high drug loading capacity(3.44%).The DOX-loaded polymeric micelles were spherical,123 nm in diameter on average,and exhibited a narrow size distribution.The in vitro experiments demonstrated that a pH decrease from 7.4 to 5.0 markedly accelerated DOX release.The micelles were well internalized by cultured breast cancer cells and the cell death rate of micelle-treated breast cancer cells was increased compared to that of free DOX-treated cells.Rapid binding of the micelles to hydroxyapatite(HA)microparticles indicated their high affinity for bone.P123-ALN/DP-8@DOX inhibited tumor growth and reduced bone resorption in a 3D cancer bone metastasis model.In vivo experiments using a breast cancer bone metastasis nude model demonstrated increased accumulation of the micelles in the tumor region and considerable antitumor activity with no organ-specific histological damage and minimal systemic toxicity.In conclusion,our study provided strong evidence that these pH-sensitive dual ligand-targeted polymeric micelles may be a successful treatment strategy for breast cancer bone metastasis.

Clinical and Therapeutic Aspects of Migraine in Brazzaville

Introduction: Migraine is the most common primary headache, and can cause significant disability. There are two types, migraine without aura and migraine with aura. The diagnosis of migraine is essentially clinical. Worldwide prevalence was estimated at 11.6% in 2009. In Africa, it is estimated at 10.4%. Objective: To describe the clinical and therapeutic aspects of migraine in Brazzaville. Patients and Methods: This was a door-to-door cross-sectional study conducted from 1st May to 1 st July 2018 in the city of Brazzaville. Subjects over 18 with clearly expressed consent were included. The questionnaire covered demographic characteristics, diagnostic criteria for migraine according to the IHS, treatments taken. The degree of disability was determined using the Migraine Disability Assessment Scale (MIDAS). Statistical analysis was performed using SPSS 22.0 for MAC. Results: Of the 1017 subjects interviewed in this study, 115 (39.9%) had migraine, including 73 women (63.47%) and 42 men (36.52%). In the group of migraine sufferers, the number of cases of definite migraine was 61 (53.04%) and that of probable migraine 54 (46.95%). For 81 migraine sufferers (70.43%), stress was the triggering factor. The frequency of attacks was weekly and monthly for 30 (26.1%) and 19 (16.5%) sufferers respectively. The location of the migraine was unilateral in 38% of cases and tilted in 24.3%. The intensity of the attack was described as moderate and severe in 41.7% and 57.4% of subjects respectively. Phonophobia/photophobia accompanied the migraine in 65.2% of cases. One hundred and eight subjects were treated. Of these, 106 (98.1%) were on medication. Eleven (10.37%) had received a medical prescription, and ninety-seven (89.8%) were self-medicating. Five and three subjects were under the care of a general practitioner and a neurologist respectively. Conclusion: Migraine is a frequent pathology in Brazzaville. Its preponderance among young people and women calls for the implementation of effective prevention strategies for these already vulnerable social groups. The form without aura was the most common type. Visual aura was the most common type. Headache-related symptoms were dominated by phonophotophobia, followed by nausea and vomiting. Almost all migraine sufferers were self-medicating, and very few were under the care of a doctor. First-line analgesics and NSAIDs were the mainstay of treatment.

Lin28 as a therapeutic target for central nervous system regeneration and repair

Axon disconnection in the central nervous system(CNS) usually causes signal transduction failure and severe functional deficits in patients with neurological disorders. Currently, there is no cure for patients with CNS axon injury and they usually suffer from life-long neurological defects(e.g., paralysis, loss of sensory function, and autonomic dysfunction) and life-threatening complications(e.g., autonomic dysreflexia).

Pulmonary embolism secondary to acute anterior ST-elevation myocardial infarction:a case report

Thrombophilia denotes a condition,whether acquired or hereditary,characterized by increased susceptibility to hypercoagulation.[1]This condition was first described in 1965,coinciding with the discovery of an inherited predisposition to venous thromboembolism(VTE)in patients deficient in antithrombin III.[2]While arterial and venous thromboses are common in hospitalized patients,acute myocardial infarction(AMI)and pulmonary embolism(PE)stand out as lifethreateningconditions.However,theoccurrenceof AMI complicated by PE is exceedingly rare,especially when considering cases where paradoxical embolism originating from a patent foramen ovale is absent.This report presents a case of AMI complicated with PE.A comprehensive understanding of the pathophysiology of this rare yet critical condition is important for ensuring prompt diagnosis and treatment.

Perspectives for delivery of therapeutics by extravasation of biodegradable microspheres in the brain

Development of therapeutics for brain diseases has remained challenging,in particular due to the difficulty of passing the blood-brain barrier.As a result,the current arsenal of therapeutics targeting the brain is limited to small,lipid-soluble drugs and there is a lack of options for treating neuroblastomas,Alzheimer’s disease,and many other devastating pathologies.Despite the advances in strategies for crossing the blood-brain barrier such as the use of nanoparticles(Hersh et al.,2022;Duan et al.,2023),such delivery systems have not yet reached clinical practice.Therefore,novel platforms for the transport of therapeutics across the blood-brain barrier remain highly desired.This specifically holds for large molecules such as monoclonal antibodies and recombinant proteins,as well as nucleotide-based therapeutics and cell therapies.Research efforts in this field are increasing exponentially,with thousands of publications in the last few years.

A novel approach to Parkinson's disease treatment with a potentially dual-acting therapeutic agent that targetsα-synuclein aggregation and neuron death

Parkinson's disease(PD),a prevalent neurodegenerative disorder,is chara cterized by the loss of dopaminergic neurons and the aggregation ofα-synuclein protein into Lewy bodies.While the current standards of therapy have been successful in providing some symptom relief,they fail to address the underlying pathophysiology of PD and as a result,they have no effect on disease progression.

Lecanemab Unveiled:Exploring Alzheimer’s Treatment Advancements,Assessing Strengths,Limitations,and Its Therapeutic Landscape Position

In the ever-evolving landscape of Alzheimer’s treatment,lecanemab(Leqembi)has emerged as a promising drug.Unlike conventional therapies that merely alleviate symptoms,lecanemab is a humanized monoclonal antibody with a distinct focus.It targets protofibrils,insoluble fibrils,amyloid oligomers,and soluble amyloid-beta protofibrils,which are known to be especially damaging to neurons,with high accuracy.

Eradication Treatment of Helicobacter pylori Infection: Evaluation of Therapeutic Strategies in N’Djamena

Background: Helicobacter pylori (Hp) infection is the most widespread bacterial infection in the world. The infection is generally acquired in childhood, but can persist into adulthood. Eradication therapy has undergone several modifications. The aim of this study was to evaluate the different therapeutic strategies used in the eradication of Helicobacter pylori infection in the Centre Hospitalier Universitaire La Reference Nationale of N’Djaména. Patients and Methods: This was a prospective, descriptive analytical study spread over one year, from September 2021 to September 2022. Patients at least 15 years of age presenting with dyspeptic symptoms, seen consecutively in a hepato-gastroenterology consultation and with a positive stool test for H. pylori infection, were included in the study. Equally, 1/3 of patients were treated with dual or triple therapy. The remaining third received quadritherapy. Results: A total of 268 patients were included in the study (mean age 38.40 ± 14.66 with extremes of 16 and 80 years). Males predominated in 58% of cases. Overall therapeutic efficacy was 88.9%. According to different therapeutic strategies, efficacy was 90.75% for dual therapy with PPI (Rabeprazole) and Amoxicillin. On the other hand, efficacy was 87% and 88.88% for PPI-based triple therapy and dual antibiotic therapy, and for PPI-based quadruple therapy and triple antibiotic therapy. Conclusion: H. pylori infection is a common disease in Chad. Dual therapy with rabeprazole combined with a high dose of amoxicillin over a period of at least two weeks showed similar if not better efficacy than triple or quadruple therapy.

MicroRNA-451a is a candidate biomarker and therapeutic target for major depressive disorder

Background Increasing evidence supports the role of microRNAs(miRNAs)in major depressive disorder(MDD),but the pathophysiological mechanism remains elusive.Aims To explore the mechanism of microRNA-451a(miR-451a)in the pathology and behaviours of depression.Methods Abnormal miRNAs such as miR-451a reported previously in the serum of patients with MDD were screened and then confirmed in a mouse model of depression induced by chronic restraint stress(CRS).Eight-week-old male C57BL/6 mice had miR-451a overexpression in the medial prefrontal cortex(mPFC)via adeno-associated virus serotype 9 vectors encoding a pri-mmu-miR-451a-GFP fusion protein followed by behavioural and pathological analyses.Finally,molecular biological experiments were conducted to investigate the potential mechanism of miR-451a against depression.Results The serum levels of miRNA-451awere significantly lower in patients with MDD,with a negative correlation with the Hamilton Depression Scale scores.Additionally,a negative association between serum miR-451a and behavioural despair or anhedonia was observed in CRS mice.Notably,miR-451a expression was significantly downregulated in the mPFC of CRS-susceptible mice.Overexpressing miR-451a in the mPFC reversed the loss of dendritic spines and the depression-like phenotype of CRS mice.Mechanistically,miR-451a could inhibit CRS-induced corticotropin-releasing factor receptor 1 expression via targeting transcription factor 2,subsequently protecting dendritic spine plasticity.Conclusions Together,these results highlighted miR-451a as a candidate biomarker and therapeutic target for MDD.

Biological,pathological,and multifaceted therapeutic functions of exosomes to target cancer

Exosomes,small tiny vesicle contains a large number of intracellular particles that employ to cause various diseases and prevent several pathological events as well in the human body.It is considered a“double-edged sword”,and depending on its biological source,the action of exosomes varies under physiological conditions.Also,the isolation and characterization of the exosomes should be performed accurately and the methodology also will vary depending on the exosome source.Moreover,the uptake of exosomes from the recipients’cells is a vital and initial step for all the physiological actions.There are different mechanisms present in the exosomes’cellular uptake to deliver their cargo to acceptor cells.Once the exosomal uptake takes place,it releases the intracellular particles that leads to activate the physiological response.Even though exosomes have lavish functions,there are some challenges associated with every step of their preparation to bring potential therapeutic efficacy.So,overcoming the pitfalls would give a desired quantity of exosomes with high purity.

Therapeutic Compliance of Hypertensive Patients Followed in Ambulatory in the Cardiology Department of Kati University Hospital

Introduction: High blood pressure is a major public health problem worldwide due to its frequency and cardiovascular complications. Adherence to treatment for chronic diseases is a global problem. The aim was to study therapeutic adherence in hypertensive patients followed in ambulatory. Materials and Methods: This was a cross-sectional, descriptive study with prospective recruitment that took place from July 1 to December 31, 2022 (6 months) in the cardiology department of the university hospital of Kati. The variables studied were sociodemographic data, cardiovascular risk factors, comorbidities, the possession of insurance and compliance (the Girerd questionnaire was used to assess adherence). Results: A total of 1182 patients were consulted, including 887 for hypertension, a frequency of 75%. Fifty-six patients were included in the study. The average age was 58.18 ± 13.25 years with extremes of 30 and 80 years. There was a female predominance (75%) with a sex ratio of 0.3. The majority of patients lived in urban areas (89.3%). Out-of-school patients accounted for 44.6%, more than half of patients or 55.4% had no income, patients with medical coverage accounted for 67.9% of cases. The main risk factors were physical inactivity (25%) followed by smoking 14.3%. More than 71% of patients had a compliance problem and the main reasons were forgetting to take the drug with 73.2%, followed by delayed treatment of 50% and drug discontinuation of 28.6%. Conclusion: Compliance is a real challenge and a major public health issue. This study allowed us to find a real problem of compliance in our hypertensive patients. There was a statistically significant relationship between drug adherence and forgetting to take the drug and drug discontinuation.

Regeneration of the heart:f rom molecular mechanisms to clinical therapeutics

Heart injury such as myocardial infarction leads to cardiomyocyte loss,fibrotic tissue deposition,and scar formation.These changes reduce cardiac contractility,resulting in heart failure,which causes a huge public health burden.Military personnel,compared with civilians,is exposed to more stress,a risk factor for heart diseases,making cardiovascular health management and treatment innovation an important topic for military medicine.So far,medical intervention can slow down cardiovascular disease progression,but not yet induce heart regeneration.In the past decades,studies have focused on mechanisms underlying the regenerative capability of the heart and applicable approaches to reverse heart injury.Insights have emerged from studies in animal models and early clinical trials.Clinical interventions show the potential to reduce scar formation and enhance cardiomyocyte proliferation that counteracts the pathogenesis of heart disease.In this review,we discuss the signaling events controlling the regeneration of heart tissue and summarize current therapeutic approaches to promote heart regeneration after injury.

Push forward LC-MS-based therapeutic drug monitoring and pharmacometabolomics for anti-tuberculosis precision dosing and comprehensive clinical management

The spread of tuberculosis(TB),especially multidrug-resistant TB and extensively drug-resistant TB,has strongly motivated the research and development of new anti-TB drugs.New strategies to facilitate drug combinations,including pharmacokinetics-guided dose optimization and toxicology studies of first-and second-line anti-TB drugs have also been introduced and recommended.Liquid chromatography-mass spectrometry(LC-MS)has arguably become the gold standard in the analysis of both endo-and exo-genous compounds.This technique has been applied successfully not only for therapeutic drug monitoring(TDM)but also for pharmacometabolomics analysis.TDM improves the effectiveness of treatment,reduces adverse drug reactions,and the likelihood of drug resistance development in TB patients by determining dosage regimens that produce concentrations within the therapeutic target window.Based on TDM,the dose would be optimized individually to achieve favorable outcomes.Pharmacometabolomics is essential in generating and validating hypotheses regarding the metabolism of anti-TB drugs,aiding in the discovery of potential biomarkers for TB diagnostics,treatment monitoring,and outcome evaluation.This article highlighted the current progresses in TDM of anti-TB drugs based on LC-MS bioassay in the last two decades.Besides,we discussed the advantages and disadvantages of this technique in practical use.The pressing need for non-invasive sampling approaches and stability studies of anti-TB drugs was highlighted.Lastly,we provided perspectives on the prospects of combining LC-MS-based TDM and pharmacometabolomics with other advanced strategies(pharmacometrics,drug and vaccine developments,machine learning/artificial intelligence,among others)to encapsulate in an all-inclusive approach to improve treatment outcomes of TB patients.

Bile acids,gut microbiota,and therapeutic insights in hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is a prevalent and aggressive liver malignancy.The interplay between bile acids(BAs)and the gut microbiota has emerged as a critical factor in HCC development and progression.Under normal conditions,BA metabolism is tightly regulated through a bidirectional interplay between gut microorganisms and BAs.The gut microbiota plays a critical role in BA metabolism,and BAs are endogenous signaling molecules that help maintain liver and intestinal homeostasis.Of note,dysbiotic changes in the gut microbiota during pathogenesis and cancer development can disrupt BA homeostasis,thereby leading to liver inflammation and fibrosis,and ultimately contributing to HCC development.Therefore,understanding the intricate interplay between BAs and the gut microbiota is crucial for elucidating the mechanisms underlying hepatocarcinogenesis.In this review,we comprehensively explore the roles and functions of BA metabolism,with a focus on the interactions between BAs and gut microorganisms in HCC.Additionally,therapeutic strategies targeting BA metabolism and the gut microbiota are discussed,including the use of BA agonists/antagonists,probiotic/prebiotic and dietary interventions,fecal microbiota transplantation,and engineered bacteria.In summary,understanding the complex BA-microbiota crosstalk can provide valuable insights into HCC development and facilitate the development of innovative therapeutic approaches for liver malignancy.

Research progress on the clinical diagnosis and treatment of COPD with pulmonary embolism

Chronic obstructive pulmonary disease(COPD)is one of the most common and important diseases leading to the death of elderly patients in the world at present.It is characterized by continuous airflow restriction and irreversible chronic airway obstruction,which can easily lead to a variety of complications and accompanying symptoms,greatly affecting the quality of life of individuals and increasing the economic burden of families and society.Pulmonary embolism(PE)is one of the complications of COPD,which can lead to pulmonary blood circulation and respiratory failure,with a high risk of death.However,because its clinical symptoms overlap with the symptoms of acute exacerbation of COPD and lack of specific clinical manifestations and laboratory tests,it is easy to be misdiagnosed and ignored,thus delaying the treatment of patients and affecting the prognosis.This article will elaborate on the clinical diagnosis and treatment of chronic obstructive pulmonary disease combined with pulmonary embolism,providing certain value for early identification of COPD combined with PE patients and the severity of the condition.