Emerging Novel Therapeutic Approaches for the Treatment of Alzheimer’s Disease

Alzheimer’s disease (AD) is caused by synaptic failure and the excessive accumulation of misfolded proteins especially Aβ and tau, and associated with memory loss and cognitive impairment. Treatment of AD mainly consists of symptomatic therapy and disease-modifying therapy (DMT). Several monotherapies including small molecules or antibodies have been evaluated through multiple clinical trials, but a very few have been approved by the USFDA to intervene the disease’s pathogenesis. Past research has shown multifactorial nature of AD, therefore, multi-target drugs were proposed to target different pathways at the same time, however, currently no rationally designed multi-target directed ligand (MTDL) has been clinically approved. Different combinations and bispecific antibodies are also under development. Novel approaches like stem cell-based therapies, microRNAs, peptides, ADCs and vaccines cast a new hope for AD treatment, however, a number of questions remained to be answered prior to their safe and effective clinical translation. This review explores the small molecules, MTDL, and antibodies (monospecific and bispecific) for the treatment of AD. Finally, future perspectives (stem cell therapy, PROTAC approaches, microRNAs, ADC, peptides and vaccines) are also discussed with regard to their clinical applications and feasibility.

An Assisted Diagnosis of Alzheimer’s Disease Incorporating Attention Mechanisms Med-3D Transfer Modeling

Alzheimer’s disease(AD)is a complex,progressive neurodegenerative disorder.The subtle and insidious onset of its pathogenesis makes early detection of a formidable challenge in both contemporary neuroscience and clinical practice.In this study,we introduce an advanced diagnostic methodology rooted in theMed-3D transfermodel and enhanced with an attention mechanism.We aim to improve the precision of AD diagnosis and facilitate its early identification.Initially,we employ a spatial normalization technique to address challenges like clarity degradation and unsaturation,which are commonly observed in imaging datasets.Subsequently,an attention mechanism is incorporated to selectively focus on the salient features within the imaging data.Building upon this foundation,we present the novelMed-3D transfermodel,designed to further elucidate and amplify the intricate features associated withADpathogenesis.Our proposedmodel has demonstrated promising results,achieving a classification accuracy of 92%.To emphasize the robustness and practicality of our approach,we introduce an adaptive‘hot-updating’auxiliary diagnostic system.This system not only enables continuous model training and optimization but also provides a dynamic platform to meet the real-time diagnostic and therapeutic demands of AD.

Zinc Oxide Nanostructures for NO_2 Gas–Sensor Applications:A Review

Because of the interesting and multifunctional properties,recently,ZnO nanostructures are considered as excellent material for fabrication of highly sensitive and selective gas sensors.Thus,ZnO nanomaterials are widely used to fabricate efficient gas sensors for the detection of various hazardous and toxic gases.The presented review article is focusing on the recent developments of NO2gas sensors based on ZnO nanomaterials.The review presents the general introduction of some metal oxide nanomaterials for gas sensing application and finally focusing on the structure of ZnO and its gas sensing mechanisms.Basic gas sensing characteristics such as gas response,response time,recovery time,selectivity,detection limit,stability and recyclability,etc are also discussed in this article.Further,the utilization of various ZnO nanomaterials such as nanorods,nanowires,nano-micro flowers,quantum dots,thin films and nanosheets,etc for the fabrication of NO2gas sensors are also presented.Moreover,various factors such as NO2concentrations,annealing temperature,ZnO morphologies and particle sizes,relative humidity,operating temperatures which are affecting the NO2gas sensing properties are discussed in this review.Finally,the review article is concluded and future directions are presented.

Antidiabetic activity of alcoholic leaves extract of Alangium lamarckii Thwaites on streptozotocin-nicotinamide induced type 2 diabetic rats

Objective:To investigate antidiabetic potential of alcoholic leaves extract of Alangium lamarekii (A.lamarckii) on streptozotocin-nicotinamide induced type 2 diabetic rats.Methods:Oral glucose tolerance test was done by inducing hyperglycemic state via administration of glucose in water(2 g/kg).Single dose of alcoholic leaves extract of.4.lamarckii(250 and 500 mg/kg,p.o.) were administered to normoglycemic,hyperglycemic rats.Type 2 diabetes was induced by single intraperitoneal injection of nicotinamide(110 mg/kg) followed by streptozotocin(65 mg/kg).The study also included estimations of blood plasma glucose,lipid profile,liver glycogen,body weight and antioxidant status in normal and diabetic rats.Results:Admistration of alcoholic extract of A.lamarekii at two dosage 250 and 500 rag/kg,p.o.did not showed any significant change in blood glucose level of normoglycemic rats(P】0.05).whereas,oral glucose tolerance test depicted reduction in blood glucose level(P【0.05).The streptozotocin-nicotinamide induced diabetic rats, significantly decreased the blood plasma glucose level(P【0.001) comparable to glibenclamide (10 mg/kg),restored the lipid profile and showed improvement in liver glycogen,body weight and antioxidant status in diabetic rats.Conclusions:Present finding demonstrated the significant antidiabetic activity of alcoholic leaves extract of.4.lamarekii.

Evaluation of phytochemical and antioxidant activities of the different fractions of Hybanthus enneaspermus (Linn.) F.Muell. (Violaceae).

Objective:To investigate the naturally occurring antioxidant for the first time from the different solvent fractions of Hybanthus enneaspermus（H.enneaspermus） Linn F.Muell.family（Violaceae）. Methods:Different fractions of H.enneaspermus were tested for total phenolic content,and in vitro antioxidant activity was measured by total antioxidant assay,DPPH assay,reducing power, nitric oxide（NO）,hydrogen peroxide（H2O2） scavenging assays.Results:The ethyl acetate（EA） fraction was found to have high levels of phenolic content[（212.15±0.79） mg GAE/g].The EA fraction exhibited higher total antioxidant capacity,higher percentage of DPPH radical scavenging activity[（127.07±2.29） Fg/mL],nitric oxide[（245.16±1.44）μg/mLJ,hydrogen peroxide[（227.38±7.18）μg/mL],deoxyribose[（270.61±8.72）μg/mL]and higher reducing power.There was a significant correlation between total phenolic content and total antioxidant activity（r =0.972）. Conclusions:These results reveal that EA fraction of H.enneaspermus has strong antioxidant potential compared with other fractions.Our further study has been extended to the isolation of the possible compound that is responsible for having antioxidant property.

Inhibitory effect of two Indian medicinal plants on aldose reductase of rat lens in vitro

Objective:To assesse the inhibitor) effect of alcoholic extract of two Indian medicinal plants namely Ceasalpinia digyna Rottler and.Alangium lamarckii Thwaits on aldose reductase（AR） of rat lens.Methods:Rats lens were enucleated through posterior approach and their homogenate was prepared and centrifuged to obtain a clear supernatant for the determination of AR activity and protein content.Results:The alcoholic extract of Ceasalpirda digyna and Alangium lamarckii had a potent inhibitory effect on the lens AR enzyme.The IC50 values of alcoholic extract of the selected plants were calculated and were（46.29±11.17） and（106.00±5.11）μg/mL,respectively. Quercetin was used as a positive control and its IC50 value was（2.95±1.53）μg/mL.Conclusions:Thus,it is concluded that alcoholic extracts of the selected plant exhibit significant inhibitory effects on AR in the rat lens in vitro.

Pedalium murex Linn.:An overview of its phytopharmacological aspects

Pedalium murex Linn(family:Pedaliaceae)(P.murex) commonly known as Large Caltrops and Gokhru(India) is a shrub found in the Southern part.Deccan region of India and in some parts of Ceylon.Different parts of the plant are used to treat various ailments like,cough,cold and as an antiseptic.Interestingly.P.murex is reported traditionally to have an excellent cure in patients with reproductive disorders which are mainly impotency in men.nocturnal emissions,gonorrhoea as well as leucorrhoea in women.The plant has also benifiled in complications like urinary track disorder as well as gastro intestinal tract disorders.Phytochemically the plant is popular for the presence of a considerable amount of diosgenin and vanillin which are regarded as an important source and useful starting materials for synthesizing steroidal contraceptive drugs and isatin alkaloids.Other phytochemicals reported in the plant includes quercetin.ursolic acid,caffeic acid,amino acids(glycine,histidine,tyrosine,threonine,aspartie acid and glutamic acid) and various classes of fatty acids(triacontanoic acid,nonacosane.tritriacontane.tetratriacontanyl and heptatriacontan-4-one).Pharmacologically,the plant have been investigated for antiulcerogenic. nephroprotective.hypolipidemic,aphrodisiac,antioxidant,antimicrobial and insecticidal activities.From all these reports it can be concluded that the plant were found to have a better profile with potential natural source for the treatment of various range of either acute or chronic disease.The overall database of our review article was collected from the scientific sources in regards with all the information ol the research article for P.murex published so far.

Review on hepatitis B virus precore/core promoter mutations and their correlation with genotypes and liver disease severity

Of 350 million people worldwide are chronically infected with hepatitis B virus(HBV)and are at risk of developing cirrhosis and hepatocellular carcinoma(HCC)later in life.HBV is the most diverse DNA virus,and its genome is composed of four open reading frames:Presurface antigen/surface antigen gene(preS/S),precore/core gene(preC/C),polymerase gene(P),and theχgene(χ).HBV produces quasispecies naturally or in response to antiviral agents because of the absence of proofreading activity amid reverse transcription and a high replication rate.The virus has 10 genotypes(A to J)with different geographical distributions.There are various HBV mutations in the HBV genome,including preC/C mutations,preS/S mutations,P gene mutations,andχgene mutations.The core promoter region plays a vital part in the replication,morphogenesis and pathogenesis of the virus.The precore region also plays a crucial role in viral replication.Both core promoter and precore mutations rescue the virus from host immune surveillance and result in the formation of mutated strains that may have altered pathogenicity.preC/C mutations are associated with liver disease progression.Precore mutations stop hepatitis B e antigen(HBeAg)production and basal core promoter mutations downregulate HBeAg production.Mutations in the basal core promoter are also associated with increased HBV replication and an increased incidence of advanced liver diseases such as cirrhosis and HCC.The emergence of antiviral-resistant mutations is the main reason for treatment failure.This review focuses mainly on preC/C promoter mutations and their correlation with genotypes and liver disease severity.Thorough perception and knowledge of HBV genetic variety and mutants could be vital to discover techniques for the prognosis and control of HBV infection.

A review on the current research on microwave processing techniques applied to graphene-based supercapacitor electrodes:An emerging approach beyond conventional heating

The various methods for microwave processing of materials exhibit numerous advantages,such as short processing times,high yield,expanded reaction conditions,high reproducibility,and high purity of products.Microwave-assisted synthesis strategies have been widely adopted for the preparation of highperformance graphene-based materials for supercapacitor electrodes.Metal oxides,mixed metal oxides,metal hydroxides,layered double hydroxides,carbon nanotubes and conducting polymers are some of the main materials which have been added to graphene derivatives for advanced composite/hybrid electrodes.This review article first provides a brief introduction and an overview of microwave heating and its advantages for processing graphene-based electrode materials.After that,a systematic survey of recently published research on microwave irradiation-assisted processing is presented,focusing on:(i)transformation of graphite/graphite oxide into graphene/graphene oxide by exfoliation and reduction;(ii)formation of graphene derivatives in various liquid and gaseous media;(iii)modification of graphene derivatives with various metal oxides/hydroxides,carbon nanotubes,and conducting polymers for use in supercapacitors.Major challenges and future perspectives for microwave-assisted processing of graphene-based materials for cutting-edge supercapacitor electrode applications are also summarized in the conclusion.

Cardiac arrhythmias detection in an ECG beat signal using fast fourier transform and artificial neural network

Cardiac Arrhythmias shows a condition of abnor-mal electrical activity in the heart which is a threat to humans. This paper presents a method to analyze electrocardiogram (ECG) signal, extract the fea-tures, for the classification of heart beats according to different arrhythmias. Data were obtained from 40 records of the MIT-BIH arrhythmia database (only one lead). Cardiac arrhythmias which are found are Tachycardia, Bradycardia, Supraventricular Tachycardia, Incomplete Bundle Branch Block, Bundle Branch Block, Ventricular Tachycardia. A learning dataset for the neural network was obtained from a twenty records set which were manually classified using MIT-BIH Arrhythmia Database Directory and docu- mentation, taking advantage of the professional experience of a cardiologist. Fast Fourier transforms are used to identify the peaks in the ECG signal and then Neural Networks are applied to identify the diseases. Levenberg Marquardt Back-Propagation algorithm is used to train the network. The results obtained have better efficiency then the previously proposed methods.

Safety and Efficacy of Neoadjuvant DOF [Docetaxel, Oxaliplatin, 5-Fluorouracil] Chemotherapy Regimen in Patients with Locally Advanced Gastric and Gastro-Esophageal Junction Cancers: A Single Center Experience from India

Background:?The role of chemotherapy in Gastric Cancer is constantly evolving?with various neoadjuvant and adjuvant strategies. Several chemotherapeutic agents are used in the treatment of locally advanced gastric cancer (LAGC) namely Platinum based compounds (Cisplatin, Oxaliplatin), Fluoropyrimidines like 5-Flurouracil [(5-FU), Capecitabine)], Taxanes (Docetaxel) and Anthracyclines (Epirubicin). Various doublet and triplet combination chemotherapy regimens have been used for neo-adjuvant chemotherapy (NACT) in LAGCs. In this study we evaluated the safety and efficacy of docetaxel based triplet regimen DOF [Docetaxel, Oxaliplatin, 5-Fluorouracil] in LAGC. Material and methods:?50 Newly diagnosed patients of Locally Advanced Gastric Cancer (stage II or III) deemed fit to receive chemotherapy were included in our study. After 3 cycles of neoadjuvant chemotherapy, patients were assessed based on radiological and pathological response.?Results: 50 Patients were included in our study of which majority were male (32), median age at presentation was 55 years and 24 patients presented with a history of gastrointestinal reflux disease (GERD). The most common hematological toxicities observed in our study were anemia (61.2%), neutropenia (42.6%, febrile neutropenia constituted 6%) and thrombocytopenia (13.2%). The most common gastro-intestinal [GI] toxicities observed in our study included nausea (69.2%), vomiting (31.2%), diarrhea (34%), oral mucositis (14%) and constipation (6.6%). We found that safety profile of DOF regimen was favorable with majority of patients tolerating the regimen well. The Overall Response Rate (68%), Disease Control Rate (96%) and Resectability Rate (80%) were higher compared to western studies. Pathological CR (17.5%), ypN0?disease status (42.5%) and nodal down staging (52%), all showed positive correlations with survival outcomes. Conclusion:?DOF regimen is an effective and feasible option for neoadjuvant treatment of LAGC in an Indian population.

NiCo_2O_4 Nano-/Microstructures as High-Performance Biosensors: A Review

Non-enzymatic biosensors based on mixed transition metal oxides are deemed as the most promising devices due to their high sensitivity,selectivity,wide concentration range,low detection limits,and excellent recyclability.Spinel NiCo2O4 mixed oxides have drawn considerable attention recently due to their outstanding advantages including large specific surface area,high permeability,short electron,and ion diffusion pathways.Because of the rapid development of non-enzyme biosensors,the current state of methods for synthesis of pure and composite/hybrid NiCo2P4 materials and their subsequent electrochemical biosensing applications are systematically and comprehensively reviewed herein.Comparative analysis reveals better electrochemical sensing of bioanalytes by one-dimensional and two-dimensional NiCo2O4 nano-/microstructures than other morphologies.Better biosensing efficiency of NiCo2O4 as compared to corresponding individual metal oxides,viz.NiO and Co3O4,is attributed to the close intrinsic-state redox couples of Ni3+/Ni2+(0.58 V/0.49 V) and Co3+/Co2+(0.53 V/0.51 V).Biosensing performance of NiCo2O4 is also significantly improved by making the composites of NiCo2O4 with conducting carbonaceous materials like graphene,reduced graphene oxide,carbon nanotubes(single and multi-walled),carbon nanofibers;conducting polymers like polypyrrole(PPy),polyaniline(PANI);metal oxides NiO,Co3O4,SnO2,MnO2;and metals like Au,Pd,etc.Various factors affecting the morphologies and biosensing parameters of the nano-/microstructured NiCo2O4 are also highlighted.Finally,some drawbacks and future perspectives related to this promising field are outlined.

Vitamin D3: Association of Low Vitamin D3 Levels with Semen Abnormalities in Infertile Males

Background: Insufficiency of vitamin D is one of the utmost general health issues all over the globe, including Pakistan;incompatible data are present on the possible relationship among serum vitamin D values and quality of semen. Objective: Lack of Vitamin D in body is related with a higher risk of various health problems including infertility. In our setup no such type of study had been conducted in the past on the relationship among serum vitamin D levels and infertility. This study was aimed to investigate male subjects with infertility and serum levels of vitamin D. Methods: This study was cross-sectional and performed on 243 male subjects who attended the clinic for evaluation of infertility from January 2016 to December 2017. Mean age of patients was 31.94 years with standard deviation of 7.52 years. The mean age of controls was 32.2 years with SD 8.42 years, age ranged between 20 years as minimum to 46 years as maximum. The minimum vitamin D level was 7.00 ng/dl while maximum 130 ng/dl, mean was 26.20 and standard deviation was 22.06 ng/ml. Levels of vitamin D were significantly low in (67%) male subjects with infertility. The mean vitamin D level of controls was 49.40 with SD of 35.98 ng/ml. 28% of controls had also vitamin D levels below the normal range, which indicates the prevalence of vitamin D deficiency in general population here in our setup. The participants were divided according to WHO (World Health Organization) 2010 criteria along with corresponding healthy control subjects. A questionnaire for evaluation of infertility in male subjects was filled by all the contestants. Results: Levels of vitamin D were significantly low in (67%) male subjects with infertility. While 28% of controls had also vitamin D levels below the normal range. Infertile male subjects with low or no sperm count were found insufficient for vitamin D in comparison to healthy control subjects. Conclusion: It was concluded from the results of current study that low levels of vitamin D are related with abnormal male reproductive function, the severity of that was subject to the amount of vitamin D insufficiency.

Sacred groves of India:repositories of a rich heritage and tools for biodiversity conservation

Sacred groves preserve a rich religious and socio-cultural heritage of Indian biodiversity from primeval times,due to their values.They act as a bridge between man and nature.Groves help to improve soil quality,replenish water resources and are pivotal for biodiversity conservation of plants and animals including rare,endemic,threatened,vulnerable species and ethnobotanical species.Most of India's sacred groves are associated with a deity or a spiritual being,who protects the grove and local people.Vegetation cover of these groves has traditional ethnobotanical value,especially in the field of ethnomedicine,which accounts for the conservation of groves over the years.Numerous plant species from sacred groves are used according to tradition and culture to prevent or cure various health problems.However,modernisation,industrialisation,increased encroachment and misuse of forest resources increasingly threaten sacred groves.These treasures of nature must be conserved by formulating and applying new laws and policies while creating awareness among people about the value of sacred groves.Toward this aim,we review the distribution,ecological and socio-cultural significance of sacred groves of India and strategies to conserve them.

Physics design of 14 MeV neutron generator facility at the Institute for Plasma Research

A high energy and high yield neutron source is a prime requirement for technological studies related to fusion reactor development. It provides a high-energy neutron environment for small-scale fusion reactor components research and testing such as tritium breeding, shielding, plasmafacing materials, reaction cross-section data study for fusion materials, etc. Along with ITER participation, the Institute of Plasma Research, India is developing an accelerator-based 14 MeV neutron source with a yield of 10^(12)n s^(-1). The design of the source is based on the deuterium–tritium fusion reaction. The deuterium beam is accelerated and delivered to the tritium target to generate 14 MeV neutrons. The deuterium beam energy and tritium availability in the tritium target are the base parameters of the accelerator-based neutron source design. The paper gives the physics design of the neutron generator facility of the Institute for Plasma Research. It covers the requirements, design basis, and physics parameters of the neutron generator. As per the analytical results generator can produce more than 1 × 10^(12)n s^(-1)with a 110 keV D^(+) ion beam of 10 mA and a minimum 5 Ci tritium target. However, the detailed simulation with the more realistic conditions of deuteron ion interaction with the tritium titanium target shows that the desired results cannot be achieved with 110 keV. The safe limit of the ion energy should be 300 keV as per the simulation. At 300 keV ion energy and 20 mA current, it reaches 1.6 × 10^(12)n s^(-1). Moreover, it was found that to ensure sufficiently long operation time a tritium target of more than 20 Ci should be used. The scope of the neutron source is not limited to the fusion reactor research studies, it is extended to other areas such as medical radioisotopes research, semiconductor devices irradiations, and many more.

Neutronic analysis of Indian helium-cooled solid breeder tritium breeding module for testing in ITER

India has proposed the helium-cooled solid breeder blanket concept as a tritium breeding module to be tested in ITER.The module has lithium titanate for tritium breeding and beryllium for neutron multiplication.Beryllium also enhances tritium breeding.A design for the module is prepared for detailed analysis.Neutronic analysis is performed to assess the tritium breeding rate,neutron distribution,and heat distribution in the module.The tritium production distribution in submodules is evaluated to support the tritium transport analysis.The tritium breeding density in the radial direction of the module is also assessed for further optimization of the design.The heat deposition profile of the entire module is generated to support the heat removal circuit design.The estimated neutron spectrum in the radial direction also provides a more in-depth picture of the nuclear interactions inside the material zones.The total tritium produced in the HCSB module is around 13.87 mg per full day of operation of ITER,considering the 400 s ON time and 1400 s dwell time.The estimated nuclear heat load on the entire module is around 474 kW,which will be removed by the high-pressure helium cooling circuit.The heat deposition in the test blanket model(TBM)is huge(around 9 GJ)for an entire day of operation of ITER,which demonstrates the scale of power that can be produced through a fusion reactor blanket.As per the Brayton cycle,it is equivalent to 3.6 GJ of electrical energy.In terms of power production,this would be around 1655 MWh annually.The evaluation is carried out using the MCNP5 Monte Carlo radiation transport code and FEDNL 2.1 nuclear cross section data.The HCSB TBM neutronic performance demonstrates the tritium production capability and high heat deposition.

Peripheral cemento-ossifying fibroma: A case report with review of literature

Peripheral cemento-ossifying fibroma(PCOF) is a rare osteogenic neoplasm that ordinarily presents as an epulis-like growth. This is of a reactive rather than neoplastic nature and its pathogenesis is uncertain. PCOF predominantly affects adolescent and young adults with greatest prevalence around 28 years. We report here a rare clinical case of PCOF of the mandible, 1 cm mesiodistally and 1.5 cm occluso-gingivally in diameter, which caused difficulty in eating and speech, in a 42-year-old female patient. She was asymptomatic for 1 year and on follow-up for 6 mo post surgically showed gingival health and normal radioopacity of bone without any recurrence. Clinical, radiographic and histological characteristics are discussed and recommendations regarding differential diagnosis, treatment and follow up are provided. The controversial varied nomenclature and possible etiopathogenesis of PCOF are emphasized.

Groundwater Quality Analysis of Safidon and Julana Blocks of District Jind, Haryana, India

We present an extensive investigation of physico-chemical parameters of water samples of Julana and Safidon blocks of District Jind, Haryana, India. Water samples were collected from different localities in cleaned polythene bottles and were analyzed for the different physico-chemical parameters like pH, electrical conductivity, total dissolved solids (TDS), total hardness (TH), calcium, magnesium, total alkalinity (TA), carbonate, bicarbonate, sodium, potassium, chloride, sulphate and fluoride. The analyzed parameters were compared with the standard desirable limits prescribed by World Health Organization (WHO), Bureau of Indian Standard (BIS) and Indian Council of Medical Research (ICMR) standards of drinking water quality parameters. For the identification of the highly correlated and interrelated water quality parameters, the correlation coefficients were calculated between different parameters and the t-test was applied for checking significance. The results showed significant variations in water quality parameters in the study areas.

Stock Market Index Prediction Using Machine Learning and Deep Learning Techniques

Stock market forecasting has drawn interest from both economists and computer scientists as a classic yet difficult topic.With the objective of constructing an effective prediction model,both linear and machine learning tools have been investigated for the past couple of decades.In recent years,recurrent neural networks(RNNs)have been observed to perform well on tasks involving sequence-based data in many research domains.With this motivation,we investigated the performance of long-short term memory(LSTM)and gated recurrent units(GRU)and their combination with the attention mechanism;LSTM+Attention,GRU+Attention,and LSTM+GRU+Attention.The methods were evaluated with stock data from three different stock indices:the KSE 100 index,the DSE 30 index,and the BSE Sensex.The results were compared to other machine learning models such as support vector regression,random forest,and k-nearest neighbor.The best results for the three datasets were obtained by the RNN-based models combined with the attention mechanism.The performances of the RNN and attention-based models are higher and would be more effective for applications in the business industry.

Immediate in-hospital outcomes after percutaneous revascularization of acute myocardial infarction complicated by cardiogenic shock

BACKGROUND Cardiogenic shock(CS)is a life-threatening complication of acute myocardial infarction with high morbidity and mortality rates.Primary percutaneous coro-nary intervention(PCI)has been shown to improve outcomes in patients with CS.AIM To investigate the immediate mortality rates in patients with CS undergoing primary PCI and identify mortality predictors.METHODS We conducted a retrospective analysis of 305 patients with CS who underwent primary PCI at the National Institute of Cardiovascular Diseases,Karachi,Pak-istan,between January 2018 and December 2022.The primary outcome was immediate mortality,defined as mortality within index hospitalization.Uni-variate and multivariate logistic regression analyses were performed to identify predictors of immediate mortality.RESULTS In a sample of 305 patients with 72.8%male patients and a mean age of 58.1±11.8 years,the immediate mortality rate was found to be 54.8%(167).Multivariable analysis identified Killip class IV at presentation[odds ratio(OR):2.0;95%co-nfidence interval(CI):1.2-3.4;P=0.008],Multivessel disease(OR:3.5;95%CI:1.8-6.9;P<0.001),and high thrombus burden(OR:2.6;95%CI:1.4-4.9;P=0.003)as independent predictors of immediate mortality.CONCLUSION Immediate mortality rate in patients with CS undergoing primary PCI remains high despite advances in treatment strategies.Killip class IV at presentation,multivessel disease,and high thrombus burden(grade≥4)were identified as independent predictors of immediate mortality.These findings underscore the need for aggressive management and close monitoring of patients with CS undergoing primary PCI,particularly in those with these high-risk characteristics.