Study on the efficacy of early treatment with pirfenidone on the lung function of patients with idiopathic pulmonary fibrosis

BACKGROUND Idiopathic pulmonary fibrosis(IPF)is classified under fibrotic interstitial pneumonia,characterized by a chronic and progressive course.The predominant clinical features of IPF include dyspnea and pulmonary dysfunction.AIM To assess the effects of pirfenidone in the early treatment of IPF on lung function in patients.METHODS A retrospective analysis was performed on 113 patients with IPF who were treated in our hospital from November 2017 to January 2023.These patients were divided into two groups:control group(n=53)and observation group(n=60).In the control group,patients received routine therapy in combination with methylprednisolone tablets,while those in the observation group received routine therapy together with pirfenidone.After applying these distinct treatment approaches to the two groups,we assessed several parameters,including the overall effectiveness of clinical therapy,the occurrence of adverse reactions(e.g.,nausea,vomiting,and anorexia),symptom severity scores,pulmonary function index levels,inflammatory marker levels,and the 6-min walk distance before and after treatment in both groups.RESULTS The observation group exhibited significantly higher rates than the control group after therapy,with a clear distinction(P<0.05).After treatment,the observation group experienced significantly fewer adverse reactions than the control group,with a noticeable difference(P<0.05).When analyzing the symptom severity scores between the two groups of patients after treatment,the observation group had significantly lower scores than the control group,with a distinct difference(P<0.05).When comparing the pulmonary function index levels between the two groups of patients after therapy,the observation group displayed significantly higher levels than the control group,with a noticeable difference(P<0.05).Evaluating the inflammatory marker data(C-reactive protein,interleukin-2[IL-2],and IL-8)between the two groups of patients after therapy,the observation group exhibited significantly lower levels than the control group,with significant disparities(P<0.05).Comparison of the 6-min walking distance data between the two groups of patients after treatment showed that the observation group achieved significantly greater distances than the control group,with a marked difference(P<0.05).CONCLUSION Prompt initiation of pirfenidone treatment in individuals diagnosed with IPF can enhance pulmonary function,elevate inflammatory factor levels,and increase the distance covered in the 6-min walk test.This intervention is conducive to effectively decreasing the occurrence of adverse reactions in patients.

PKHD1L1 blocks the malignant behavior of lung adenocarcinoma cells and restricts tumor growth by regulating CBX7

Objective:To explore the role of polycystic kidney and hepatic disease 1-like 1(PKHD1L1)in lung adenocarcinoma(LUAD).Methods:Bioinformatics tools were utilized to examine the clinical profile of PKHD1L1 and chromobox protein homolog 7(CBX7)in LUAD.The Cell Counting Kit-8,colony formation,terminal deoxynucleotidyl transferase dUTP nick end labeling,Transwell,and wound-healing assays were carried out to assess the proliferative,apoptotic,invasive,and migrative capacities of the cells.Furthermore,the interrelation between PKHD1L1 and CBX7 was validated using a co-immunoprecipitation assay.A LUAD mice model was constructed by subcutaneous injection of A549 cells.Finally,immunohistochemical staining was performed to evaluate CBX7 and Ki67 expression.Results:PKHD1L1 was downregulated in LUAD and predicted dismal outcomes in patients with LUAD.PKHD1L1 upregulation repressed the proliferative,invasive,and migrative capabilities of A549 cells and exacerbated the apoptotic rate.Additionally,PKHD1L1 may bind to CBX7 and positively modulate CBX7 expression.CBX7 deletion partly abrogated the effects of PKHD1L1 upregulation on the cellular biological activities in A549 cells.Furthermore,the PKHD1L1/CBX7 axis regulates the Hippo signaling pathway in A549 cells.PKHD1L1 restricted tumor growth in LUAD xenograft mice;this was partly abolished by CBX7 knockdown.Conclusion:PKHD1L1 can hinder LUAD progression by regulating CBX7-mediated Hippo signaling.

Prognostic and immunological roles of heat shock protein A4 in lung adenocarcinoma

BACKGROUND Heat shock protein A4(HSPA4)belongs to molecular chaperone protein family which plays important roles within variable cellular activities,including cancer initiation and progression.However,the prognostic and immunological significance of HSPA4 in lung adenocarcinoma(LUAD)has not been revealed yet.AIM To explore the prognostic and immunological roles of HSPA4 to identify a novel prognostic biomarker and therapeutic target for LUAD.METHODS We assessed the prognostic and immunological significance of HSPA4 in LUAD using data from The Cancer Genome Atlas database.The association between HSPA4 expression and clinical-pathological features was assessed through Kruskal-Wallis and Wilcoxon signed-rank test.Univariate/multivariate Cox regression analyses and Kaplan-Meier curves were employed to evaluate prognostic factors,including HSPA4,in LUAD.Gene set enrichment analysis(GSEA)was conducted to identify the key signaling pathways associated with HSPA4.The correlation between HSPA4 expression and cancer immune infiltration was evaluated using single-sample gene set enrichment analysis(ssGSEA).RESULTS Overexpressing HSPA4 was significantly related to advanced pathologic TNM stage,advanced pathologic stage,progression disease status of primary therapy outcome and female subgroups with LUAD.In addition,increased HSPA4 expression was found to be related to worse disease-specific survival and overall survival.GSEA analysis indicated a significant correlation between HSPA4 and cell cycle regulation and immune response,particularly through diminishing the function of cytotoxicity cells and CD8 T cells.The ssGSEA algorithm showed a positive correlation between HSPA4 expression and infiltrating levels of Th2 cells,while a negative correlation was observed with cytotoxic cell infiltration levels.CONCLUSION Our findings indicate HSPA4 is related to prognosis and immune cell infiltrates and may act as a novel prognostic biomarker and therapeutic target for LUAD.

Molecular Epidemiology and Clinical Characteristics of Hand, Foot and Mouth Disease in North Sichuan Region, China, 2018-2023: A Descriptive Study

Background: Hand, foot and mouth disease (HFMD) remains an important public health problem in China. Many studies on the epidemiological characteristics of HFMD have been reported, but studies in North Sichuan region have been neglected. Methods: HFMD-related enterovirus infected cases were clinically confirmed and underwent real-time RT-PCR (rRT-PCR) from May 2018 to October 2023 in Guangyuan Central Hospital. Results: During 2018-2023, other EV (437 cases, 81.08%) was the most predominant serotype followed by CV-A16 (94 cases, 17.44%), EV-A71 (8 cases, 1.48%) was the least predominant serotype. Peak infections occurred in July and October. There were no significant differences in gender, age and serotypes. HFMD was concentrated in children under 47 months of age, with the highest incidence in children aged 12 - 23 months and the highest proportion of other EV infections in the whole age group. COVID-19 did not cause significant changes in gender, age and serotype. Overall, there was a significant increase in the proportion of children aged 12 - 23 months infected with CV-A16, and an increase in the proportion of children aged over 36 months infected with other EVs. Conclusions: The incidence of HFMD caused by EV-A71 has decreased significantly, and other EVs have become the main pathogens of HFMD in North Sichuan region in recent years. In the prevention and control of CV-A16, more attention should be paid to children aged 12 - 23 months and the dominant serotype should be closely monitored. Our study highlights the importance of developing of new diagnostic reagents and vaccines for the prevention and control of enterovirus infection. This study for the first time provides insights into district interventions to local conditions.

Traumatic brain injury and variants of shock index

Traumatic Brain Injury is a major cause of death and long-term disability.The early identification of patients at high risk of mortality is important for both management and prognosis.Although many modified scoring systems have been developed for improving the prediction accuracy in patients with trauma,few studies have focused on prediction accuracy and application in patients with traumatic brain injury.The shock index(SI)which was first introduced in the 1960s has shown to strongly correlate degree of circulatory shock with increasing SI.In this editorial we comment on a publication by Carteri et al wherein they perform a retrospective analysis studying the predictive potential of SI and its variants in populations with severe traumatic brain injury.

Analysis of the Effect of Continuous Nursing Care in Patients with COPD

Objective:to study the effect of continuous nursing intervention in patients with chronic obstructive pulmonary disease(COPD).Methods:In this paper,56 COPD patients were selected and grouped by drawing lots,with 28 cases in each group.The study group underwent continuous nursing intervention,while the control group underwent conventional care,and the parameters of both groups of patients were compared.Results:Compared with the control group,the patients in the study group had a significantly higher forced expiratory volume in one second to forced vital capacity ratio(FEV1/FVC),a significantly lower COPD Assessment Test(CAT)score,and Hamilton Depression(HAM-D)score,and a significantly higher 6-Minute Walk Test(6WMT)score after nursing care.Besides,their self-care ability score and SaO_(2)were significantly higher,while their PaCO_(2)and coagulation indexes were significantly lower(P<0.05).Conclusion:Continuous nursing intervention is beneficial for COPD patients.

National survey of the awareness and implementation status of early pulmonary rehabilitation for patients with critical illness in departments of pulmonary and critical care medicine in 2019

To the Editor:The aim of early pulmonary rehabilitation(PR)in the intensive care unit(ICU)is to reduce the incidence of post-ICU syndrome,increase the number of ventilator-free days,reestablish and improve functional capacity,improve health-related life quality,promote mental health,and enhance participation in everyday life.PR in the ICU is highly effective and plays an important role in recovery of patients with reduced exercise endurance,functional capacity,and health-related life quality.Several surveys outside China have assessed the implementation of early rehabilitation in the ICU,[1]but there are few data from China.This study aimed to investigate the awareness and implementation of early PR in secondary-and tertiary-class hospitals with pulmonary and critical care medicine(PCCM)standardized certification.PCCM staff members were recruited to fill out a selfdesigned questionnaire.We defined early PR as PR within 5 days of ICU admission.

Bioengineered exosomal-membrane-camouflaged abiotic nanocarriers: neurodegenerative diseases, tissue engineering and regenerative medicine

A bio-inspired strategy has recently been developed for camouflaging nanocarriers with biomembranes,such as natural cell membranes or subcellular structure-derived membranes.This strategy endows cloaked nanomaterials with improved interfacial properties,superior cell targeting,immune evasion potential,and prolonged duration of systemic circulation.Here,we summarize recent advances in the production and application of exosomal membrane-coated nanomaterials.The structure,properties,and manner in which exosomes communicate with cells are first reviewed.This is followed by a discussion of the types of exosomes and their fabrication methods.We then discuss the applications of biomimetic exosomes and membrane-cloaked nanocarriers in tissue engineering,regenerative medicine,imaging,and the treatment of neurodegenerative diseases.Finally,we appraise the current challenges associated with the clinical translation of biomimetic exosomal membrane-surface-engineered nanovehicles and evaluate the future of this technology.

Critical respiratory failure due to pregnancy complicated by COVID-19 and bacterial coinfection:A case report

BACKGROUND In the past 3 years,the global pandemic of coronavirus disease 2019(COVID-19)has posed a great threat to human life and safety.Among the causes of death in COVID-19 patients,combined or secondary bacterial infection is an important factor.As a special group,pregnant women experience varying degrees of change in their immune status,cardiopulmonary function,and anatomical structure during pregnancy,which puts them at higher risk of contracting COVID-19.COVID-19 infection during pregnancy is associated with increased adverse events such as hospitalisation,admission to the intensive care unit,and mechanical ventilation.Therefore,pregnancy combined with coinfection of COVID-19 and bacteria often leads to critical respiratory failure,posing severe challenges in the diagnosis and treatment process.CASE SUMMARY We report a case of COVID-19 complicated with Staphylococcus aureus(S.aureus)coinfection in a pre-gnant woman at 34 wk of gestation.Her rapid progression of pulmonary lesions caused severe respiratory failure,and she received noninvasive ventilator-assisted respiratory treatment.Subsequently,we delivered a foetus via emergency caesarean section after accelerating the maturity of the foetal pulmonary system,and the respiratory condition of the puerperant woman significantly improved after the delivery of the foetus.Lavage fluid was taken under tracheoscopy to quickly search for pathogens by the metagenomic nextgeneration sequencing(mNGS),and both COVID-19 and S.aureus were detected.After targeted anti-infective treatment,the maternal condition gradually improved,and the patient was discharged from the hospital.CONCLUSION The coinfection of pregnancy with COVID-19 and bacteria often leads to critical respiratory failure,which is a great challenge in the process of diagnosis and treatment.It is crucial to choose the right time to deliver the foetus and to quickly find pathogens by mNGS.

Key elements and checklist of shared decisionmaking conversation on life-sustaining treatment in emergency:a multispecialty study from China

BACKGROUND:Shared decision-making(SDM)has broad application in emergencies.Most published studies have focused on SDM for a certain disease or expert opinions on future research gaps without revealing the full picture or detailed guidance for clinical practice.This study is to investigate the optimal application of SDM to guide life-sustaining treatment(LST)in emergencies.METHODS:This study was a prospective two-round Delphi consensus-seeking survey among multiple stakeholders at the China Consortium of Elite Teaching Hospitals for Residency Education.Participants were identified based on their expertise in medicine,law,administration,medical education,or patient advocacy.All individual items and questions in the questionnaire were scored using a 5-point Likert scale,with responses ranging from"very unimportant"(a score of 1)to"extremely important"(a score of 5).The percentages of the responses that had scores of 4-5on the 5-point Likert scale were calculated.A Kendall’s W coefficient was calculated to evaluate the consensus of experts.RESULTS:A two-level framework consisting of 4 domains and 22 items as well as a ready-touse checklist for the informed consent process for LST was established.An acceptable Kendall’s W coefficient was achieved.CONCLUSION:A consensus-based framework supporting SDM during LST in an emergency department can inform the implementation of guidelines for clinical interventions,research studies,medical education,and policy initiatives.

Pulmonary reversed halo cycles and consolidations after immunotherapy:A case report

BACKGROUND Immune checkpoint inhibitor-associated interstitial lung disease(ICI-ILD)and opportunistic pneumonias are the main pulmonary complications during immunotherapy for malignancies.The organizing pneumonia(OP)pattern is one of the common radiological manifestations of ICI-ILD,and OP is the most common cause of reversed halo cycles and consolidations.However,opportunistic pneumonias should be excluded.CASE SUMMARY In this report,we described a case of a 44-year-old man with esophageal cancer who showed multiple reversed-halo cycles and consolidations on chest computed tomography(CT)after he had a cold during immunotherapy.He was diagnosed with esophageal squamous-cell cancer(T2NIM0)after surgery.Then,he was successfully treated with 6 cycles of chemotherapy plus tislelizumab,one cycle of radiotherapy and 9 cycles of tislelizumab.Two months later,he complained of low-grade fever and cough with nonpurulent sputum after he had a cold.Community-acquired pneumonia was considered,but moxifloxacin was ineffective.Chest CT showed multiple reversed-halo cycles and consolidations.Mycobacterium tuberculosis was identified with next-generation sequence analysis of bronchoalveolar lavage fluid(BALF).Two months later,he improved with standard anti-tuberculosis medications.Both the cycles and consolidations disappeared in the repeat CT after 6 mo of medications.CONCLUSION When chest CT shows reversed-halo cycles and consolidations in patients during anticancer immunotherapy,both ICI-ILD and infectious pneumonia should be considered.BALF microbiological analysis was helpful to differentiate them.

Initial steps on the analysis of the underlying pharmacological mechanisms of Wendan decoction on sudden deafness using network pharmacology and molecular docking

Background:Despite its widespread therapeutic use and effectiveness,the underlying pharmacologic mechanisms of Wendan decoction(WDD)and how it works to treat sudden deafness(SD)remain unclear.In this study,the pharmacological mechanisms of WDD underlying SD were analyzed using network pharmacology and molecular docking.Methods:The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)was employed to identify the active compounds and target genes of WDD,and genes associated with SD were screened on five databases.RGUI conducted Gene Ontology(GO)functional and the Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses.A compound-target network was established using Cytoscape,and the STRING database created a protein-protein interaction(PPI)network to identify the key compounds and targets.Subsequently,a network of crucial compound-target was generated for further molecular docking analysis.For molecular docking simulations of the macromolecular target proteins and their matching ligand molecules,AutoDock Vina and AutoDockTool were utilized.Results:TCMSP identified 162 active target genes and 36 active compounds for WDD.The active target genes were compared with the 2271 genes associated with SD to identify 70 intersecting active target genes linked to 34 active compounds.The GO functional enrichment and KEGG pathway enrichment analyses were undertaken,and compound–target,and PPI networks were built.The key compounds and protein targets were identified and integrated to form a key compound–target network.Eventually,molecular docking was performed to investigate the interactions of the protein targets with their respective compounds.Conclusion:This study highlights the mechanisms of multi-compounds,targets,and pathways of WDD acting on SD and provides further evidence of crucial compounds and their matching target proteins of WDD acting on SD.

Expert consensus on the monitoring and treatment of sepsis-induced immunosuppression

Emerged evidence has indicated that immunosuppression is involved in the occurrence and development of sepsis.To provide clinical practice recommendations on the immune function in sepsis,an expert consensus focusing on the monitoring and treatment of sepsis-induced immunosuppression was developed.Literature related to the immune monitoring and treatment of sepsis were retrieved from PubMed,Web of Science,and Chinese National Knowledge Infrastructure to design items and expert opinions were collected through an online questionnaire.Then,the Delphi method was used to form consensus opinions,and RAND appropriateness method was developed to provide consistency evaluation and recommendation levels for consensus opinions.This consensus achieved satisfactory results through two rounds of questionnaire survey,with 2 statements rated as perfect consistency,13 as very good consistency,and 9 as good consistency.After summarizing the results,a total of 14 strong recommended opinions,8 weak recommended opinions and 2 non-recommended opinions were produced.Finally,a face-to-face discussion of the consensus opinions was performed through an online meeting,and all judges unanimously agreed on the content of this consensus.In summary,this expert consensus provides a preliminary guidance for the monitoring and treatment of immunosuppression in patients with sepsis.

Clinical Significance and Levels of NLRP3,MUC5AC,and MUC5B in Asthma

Objective:To explore the role of NLRP3 in mucus hypersecretion in asthmatic patients.Methods:From January 2020 to June 2022,90 patients with asthma and 60 healthy patients under the Department of Pulmonary and Critical Care Medicine of the First Affiliated Hospital of Xi’an Medical University were selected.Immunohistochemistry and enzyme-linked immunosorbent assay were performed.NLRP3 inflammasome and mucins MUC5AC and MUC5B levels in lung tissue and sputum were detected.Results:Compared to the healthy control group,the asthma group had significantly higher sputum MUC5A(20.12±5.07 versus 36.21±6.13)and NLRP3(72.31±15.13 versus 119.21±31.21)levels(P<0.05)but lower MUC5B levels(1.35±0.12 versus 0.53±0.11,P<0.05).Immunohistochemistry showed that NLRP3,MUC5AC,and MUC5B expressions were consistent with the sputum results.Conclusion:NLRP3 and MUC5AC levels are significantly increased in asthmatic patients,whereas MUC5B levels are reduced in these patients.They can be used as targets for the diagnosis and treatment of asthma.

An intelligent prediction model of epidemic characters based on multi-feature

The epidemic characters of Omicron(e.g.large-scale transmission)are significantly different from the initial variants of COVID-19.The data generated by large-scale transmission is important to predict the trend of epidemic characters.However,the re-sults of current prediction models are inaccurate since they are not closely combined with the actual situation of Omicron transmission.In consequence,these inaccurate results have negative impacts on the process of the manufacturing and the service industry,for example,the production of masks and the recovery of the tourism industry.The authors have studied the epidemic characters in two ways,that is,investigation and prediction.First,a large amount of data is collected by utilising the Baidu index and conduct questionnaire survey concerning epidemic characters.Second,theβ-SEIDR model is established,where the population is classified as Susceptible,Exposed,Infected,Dead andβ-Recovered persons,to intelligently predict the epidemic characters of COVID-19.Note thatβ-Recovered persons denote that the Recovered persons may become Sus-ceptible persons with probabilityβ.The simulation results show that the model can accurately predict the epidemic characters.

Clinical evolution of antisynthetase syndrome-associated interstitial lung disease after COVID-19 in a man with Klinefelter syndrome:A case report

BACKGROUND This study presents a case of rapidly developing respiratory failure due to antisynthetase syndrome(AS)following coronavirus disease 2019(COVID-19)in a 33-year-old man diagnosed with Klinefelter syndrome(KS).CASE SUMMARY A 33-year-old man with a diagnosis of KS was admitted to the Department of Pulmonary and Critical Care Medicine of a tertiary hospital in China for fever and shortness of breath 2 wk after the onset of COVID-19.Computed tomography of both lungs revealed diffuse multiple patchy heightened shadows in both lungs,accompanied by signs of partial bronchial inflation.Metagenomic next-generation sequencing of the bronchoalveolar lavage fluid suggested absence of pathogen.A biopsy specimen revealed organizing pneumonia with alveolar septal thickening.Additionally,extensive auto-antibody tests showed strong positivity for anti-SSA,anti-SSB,anti-Jo-1,and anti-Ro-52.Following multidisciplinary discussions,the patient received a final diagnosis of AS,leading to rapidly progressing respiratory failure.CONCLUSION This study underscores the clinical progression of AS-associated interstitial lung disease subsequent to viral infections such as COVID-19 in patients diagnosed with KS.

Optimization of tracheoesophageal fistula model established with Tshaped magnet system based on magnetic compression technique

BACKGROUND The magnetic compression technique has been used to establish an animal model of tracheoesophageal fistula(TEF),but the commonly shaped magnets present limitations of poor homogeneity of TEF and poor model control.We designed a Tshaped magnet system to overcome these problems and verified its effectiveness via animal experiments.AIM To investigate the effectiveness of a T-shaped magnet system for establishing a TEF model in beagle dogs.METHODS Twelve beagles were randomly assigned to groups in which magnets of the Tshaped scheme(study group,n=6)or normal magnets(control group,n=6)were implanted into the trachea and esophagus separately under gastroscopy.Operation time,operation success rate,and accidental injury were recorded.After operation,the presence and timing of cough and the time of magnet shedding were observed.Dogs in the control group were euthanized after X-ray and gastroscopy to confirm establishment of TEFs after coughing,and gross specimens of TEFs were obtained.Dogs in the study group were euthanized after X-ray and gastroscopy 2 wk after surgery,and gross specimens were obtained.Fistula size was measured in all animals,and then harvested fistula specimens were examined by hematoxylin and eosin(HE)and Masson trichrome staining.RESULTS The operation success rate was 100%for both groups.Operation time did not differ between the study group(5.25 min±1.29 min)and the control group(4.75 min±1.70 min;P=0.331).No bleeding,perforation,or unplanned magnet attraction occurred in any animal during the operation.In the early postoperative period,all dogs ate freely and were generally in good condition.Dogs in the control group had severe cough after drinking water at 6-9 d after surgery.X-ray indicated that the magnets had entered the stomach,and gastroscopy showed TEF formation.Gross specimens of TEFs from the control group showed the formation of fistulas with a diameter of 4.94 mm±1.29 mm(range,3.52-6.56 mm).HE and Masson trichrome staining showed scar tissue formation and hierarchical structural disorder at the fistulas.Dogs in the study group did not exhibit obvious coughing after surgery.X-ray examination 2 wk after surgery indicated fixed magnet positioning,and gastroscopy showed no change in magnet positioning.The magnets were removed using a snare under endoscopy,and TEF was observed.Gross specimens showed well-formed fistulas with a diameter of 6.11 mm±0.16 mm(range,5.92-6.36 mm),which exceeded that in the control group(P<0.001).Scar formation was observed on the internal surface of fistulas by HE and Masson trichrome staining,and the structure was more regular than that in the control group.CONCLUSION Use of the modified T-shaped magnet scheme is safe and feasible for establishing TEF and can achieve a more stable and uniform fistula size compared with ordinary magnets.Most importantly,this model offers better controllability,which improves the flexibility of follow-up studies.

Subclinical hepatitis E virus genotype 1 infection:The concept of“dynamic human reservoir”

Hepatitis E virus(HEV)is hyperendemic in South Asia and Africa accounting for half of total Global HEV burden.There are eight genotypes of HEV.Among them,the four common ones known to infect humans,genotypes 1 and 2 are prevalent in the developing world and genotypes 3 and 4 are causing challenge in the industrialized world.Asymptomatic HEV viremia in the general population,especially among blood donors,has been reported in the literature worldwide.The clinical implications related to this asymptomatic viremia are unclear and need further exploration.Detection of viremia due to HEV genotype 1 infection,apparently among healthy blood donors is also reported without much knowledge about its infection rate.Similarly,while HEV genotype 3 is known to be transmitted via blood transfusion in humans and has been subjected to screening in many European nations,instances of transmission have also been documented albeit without significant clinical consequences.Epidemiology of HEV genotype 1 in endemic areas often show waxing and waning pattern.Occasional sporadic occurrence of HEV infection interrupted by outbreaks have been frequently seen.In absence of known animal reservoir,where HEV exists in between outbreak is a mystery that needs further exploration.However,occurrence of asymptomatic HEV viremia due to HEV genotype 1 during epidemiologically quiescent period may explain that this phenomenon may act as a dynamic reservoir.Since HEV genotype 1 infection cannot cause chronicity,subclinical transient infection and transmission of virus might be the reason it sustains in interepidemic period.This might be the similar phenomenon with SARS COVID-19 corona virus infection which is circulating worldwide in distinct phases with peaks and plateaus despite vaccination against it.In view of existing evidence,we propose the concept of“Dynamic Human Reservoir.”Quiescent subclinical infection of HEV without any clinical consequences and subsequent transmission may contribute to the existence of the virus in a community.The potential for transmitting HEV infection by asymptomatic HEV infected individuals by fecal shedding of virus has not been reported in literature.This missing link may be a key to Pandora's box in understanding epidemiology of HEV infection in genotype 1 predominant region.

Critical care practice in India:Results of the intensive care unit need assessment survey(ININ2018)

BACKGROUND A diverse country like India may have variable intensive care units(ICUs)practices at state and city levels.AIM To gain insight into clinical services and processes of care in ICUs in India,this would help plan for potential educational and quality improvement interventions.METHODS The Indian ICU needs assessment research group of diverse-skilled individuals was formed.A pan-India survey"Indian National ICU Needs"assessment(ININ 2018-I)was designed on google forms and deployed from July 23rd-August 25th,2018.The survey was sent to select distribution lists of ICU providers from all 29 states and 7 union territories(UTs).In addition to emails and phone calls,social medial applications-WhatsApp™,Facebook™and LinkedIn™were used to remind and motivate providers.By completing and submitting the survey,providers gave their consent for research purposes.This study was deemed eligible for category-2 Institutional Review Board exempt status.RESULTS There were total 134 adult/adult-pediatrics ICU responses from 24(83%out of 29)states,and two(28%out of 7)UTs in 61 cities.They had median(IQR)16(10-25)beds and most,were mixed medical-surgical,111(83%),with 108(81%)being adult-only ICUs.Representative responders were young,median(IQR),38(32-44)years age and majority,n=108(81%)were males.The consultants were,n=101(75%).A total of 77(57%)reported to have 24 h in-house intensivist.A total of 68(51%)ICUs reported to have either 2:1 or 2≥:1 patient:nurse ratio.More than 80%of the ICUs were open,and mixed type.Protocols followed regularly by the ICUs included sepsis care,ventilator-associated pneumonia(83%each);nutrition(82%),deep vein thrombosis prophylaxis(87%),stress ulcer prophylaxis(88%)and glycemic control(92%).Digital infrastructure was found to be poor,with only 46%of the ICUs reporting high-speed internet availability.CONCLUSION In this large,national,semi-structured,need-assessment survey,the need for improved manpower including;in-house intensivists,and decreasing patient-tonurse ratios was evident.Sepsis was the most common diagnosis and quality and research initiatives to decrease sepsis mortality and ICU length of stay could be prioritized.Additionally,subsequent surveys can focus on digital infrastructure for standardized care and efficient resource utilization and enhancing compliance with existing protocols.

Causal relationship between feelings and cognitive decline:An univariable and multivariable Mendelian randomization study

BACKGROUND While the impact of depression on cognition is well-documented,the relationship between feelings and cognition has received limited attention.AIM To explore the potential association between feelings and cognition with a twosample Mendelian randomization(MR)analysis.METHODS Our analysis utilized genome-wide association data on various feelings(fed-up feelings,n=453071;worrier/anxious feelings,n=450765;guilty feelings,n=45-0704;nervous feelings,n=450700;sensitivity/hurt feelings,n=449419;miserableness,n=454982;loneliness/isolation,n=455364;happiness,n=152348)in the European population and their impact on cognitive functions(intelligence,n=269867).Conducting a univariable MR(UVMR)analysis to assess the relationship between feelings and cognition.In this analysis,we applied the inverse variance weighting(IVW),weighted median,and MR Egger methods.Additionally,we performed sensitivity analysis(leave-one-out analysis),assessed heterogeneity(using MR-PRESSO and Cochran’s Q test),and conducted multiple validity test(employing MR-Egger regression).Subsequently,a multivariable MR(MVMR)analysis was employed to examine the impact of feelings on cognition.IVW served as the primary method in the multivariable analysis,complemented by median-based and MR-Egger methods.RESULTS In this study,UVMR indicated that sensitivity/hurt feelings may have a negative causal effect on cognition(OR=0.63,95%CI:0.43-0.92,P=0.017).After adjustment of other feelings using MVMR,a direct adverse causal effect on cognition was observed(OR_(MVMR)=0.39,95%CI:0.17-0.90,P_(MVMR)=0.027).While a potential increased risk of cognitive decline was observed for fed-up feelings in the UVMR analysis(ORUVMR=0.64,95%CI:0.42-0.97,PUVMR=0.037),this effect disappeared after adjusting for other feelings(OR_(MVMR)=1.42,95%CI:0.43-4.74,P_(MVMR)=0.569).These findings were generally consistent across MV-IVW,median-based,and MR-Egger analyses.MR-Egger regression revealed pleiotropy in the impact of worrier/anxious feelings on cognition,presenting a challenge in identifying the effect.Notably,this study did not demonstrate any significant impact of guilty feelings,nervous feelings,miserableness,or loneliness/isolation on cognition.Due to a limited number of instrumental variables for happiness,this study was unable to analyze the relationship between happiness and cognition.CONCLUSION This MR study finds that sensitivity/hurt feelings are associated with cognitive decline,while the link between worrier/anxious feelings and cognition remains inconclusive.Insufficient evidence supports direct associations between happiness,guilty feelings,nervous feelings,miserableness,loneliness/isolation,and cognition.