Gut microbiota changes associated with frailty in older adults:A systematic review of observational studies

BACKGROUND Frailty is a complex aging-related syndrome characterized by a cumulative loss of physiological reserve and increased vulnerability to adverse clinical outcomes,including falls,disability,incapacity and death.While an increasing number of studies suggest that the gut microbiota may play a key role in the pathophy-siology of frailty,direct evaluation of the association between gut microbiome alterations and frailty in older adults remains limited.AIM Seven electronic databases(China National Knowledge Infrastructure,VIP,SinoMed,Wanfang,PubMed,Web of Science and EMBASE)were searched for articles published before October 31,2023 to identify observational studies that compared the microbiomes of older adults with and without frailty.The diversity and composition of the gut microbiota were the main outcomes used to analyze the associations of changes in the gut microbiota with frailty in older adults.The quality of the included studies was assessed via the Newcastle-Ottawa Scale and the Agency for Healthcare Research and Quality.RESULTS Eleven observational studies with 912 older adults were included in this review.Consistent results revealed a significant difference in the gut microbiota composition between frail and non-frail older adults,with a significant decrease inαdiversity and a significant increase inβdiversity in frail older adults.The pooled results revealed that at the phylum level,four microbiota(Actinobacteria,Proteo-bacteria,Verrucomicrobia and Synergistetes)were significantly enriched,and two microbiota(Firmicutes and Fusobacteria)were significantly depleted in frail older adults.At the family level,the results consistently revealed that the abundances of 6 families,most of which belong to the Actinobacteria or Proteo-bacteria phylum,were greater in frail than in non-frail older adults.At the genus or species level,consistent results from more than two studies revealed that the abundances of the genera Prevotella,Faecalibacterium,and Roseburia were significantly lower in frail older adults;individual studies revealed that the abundances of some genera or species(e.g.,Megamonas,Blautia,and Megasphaera)were significantly lower,whereas those of other genera or species(e.g.,Bifidobacterium,Oscillospira,Ruminococcus and Pyramidobacter)were significantly greater in frail older adults.CONCLUSION This systematic review suggests that changes in the gut microbiota are associated with frailty in older adults,which is commonly reflected by a reduction in beneficial species and an increase in pathogenic species.However,further studies are needed to confirm these findings.

Red meat intake and the risk of endometrial cancer:Metaanalysis of observational studies

AIM:To evaluate whether red meat intake is related to the risk of endometrial cancer(EC) using meta-analysis.METHODS:We searched Pub Med,EMBASE,and the Cochrane Library up to June 2013,using common keywords related to red meat and EC.Case-control studies and cohort studies comparing the risk of endometrial cancer among categories by the amount of intake were included.Eleven case-control studies and five cohort studies met our criteria.We performed a conventional and a dose-response meta-analysis of case-control studies using the Der Simonian-Laird method for random-effects.For cohort studies we performed a conventional meta-analysis.Publication bias was evaluated using Egger's test.RESULTS:In the meta-analysis of 11 case-control studies including 5419 cases and 12654 controls,higher red meat consumption was associated with an increased risk of EC [summary relative risk(SRR) = 1.43,95%CI:1.15-1.79;I2 = 73.3% comparing extreme intake categories).In a dose-response analysis,for red meat intake of 100 g/d,SRR was 1.84(95%CI:1.64-2.05).In contrast,in the meta-analysis of five prospective studies including a total of 2549 cases among 247746 participants,no significant association between red meat intake and EC risk(SRR = 0.97,95%CI:0.85-1.11;I2 = 4.9% comparing extreme intake categories) was observed.CONCLUSION:Our meta-analysis found a significantlinear association between red meat intake and EC risk based on case-control studies but this was not confirmed in prospective studies.

Determination of Causal Effect in Observational Studies： Analysis of Correlated Data with Binary End-Points

Identifying the causal impact of＇ some intervention challenging when one is faced with correlated binary end-points in observational studies is a challenging task, and it is even more The statistical literature on analyzing such data is well documented. Dependence between observations from the same study subject in correlated data renders invalid the usual chi-square tests of independence and inflates the variance ofparameter estimates. Disaggregated approaches such as hierarchical linear models which are able to adjust for individual level covariate：s are favoured in the analysis of such data, thereby gaining power over aggregated and individual-level analyses. In this article the authors, therefore, address the issue of analyzing correlated data with dichotomous end-points by using hierarchical logistic regression, a generalization of the standard logistic regression model for independent outcomes.

Experimental Design of Observational Studies in Real-World Study

Objective To introduce the design of observational trials under real-world study(RWS),and to provide guidance for clinical development of new research trials and reference for real-world researchers.Methods Relevant literature of RWS and observational experiments at home and abroad were reviewed and analyzed,and then the design of observational studies was summarized under RWS.Results and Conclusion The data and information provided in observational studies not only help to further verify the clinical study results obtained by randomized controlled trial(RCT)in clinical practice,but also objectively reflect the real situation in the process of clinical research and application.

Partial Least Squares Method for Treatment Effect in Observational Studies with Censored Outcomes

To estimate the true treatment effect on a censored outcome in observational studies, potential confounding effect and complex heterogeneity in the treatment assignment have to be properly adjusted. In this article, we demonstrate that the partial least squares method could be a valuable tool in this regard. It is showed that the partial least squares method not only can adequately account for the heterogeneity in treatment assignment, but also be robust to treatment assignment model misspecifications. Numerical results show that the partial least squares estimator is more efficient and robust. A real data set is analyzed to illustrate the proposed method.

Analysis of therapeutic effect of cell reduction combined with intraperitoneal thermoperfusion chemotherapy in treatment of peritoneal pseudomyxoma

BACKGROUND Pseudomyxoma peritonei is a rare tumor that can produce a biological behavior similar to that of a malignant tumor.Surgical resection combined with chemo-therapy is the traditional treatment method,but the effect is not good.Cell reduction(CRS)combined with intraperitoneal thermoperfusion chemotherapy(HIPEC)has become a new method for the treatment of peritoneal pseudomy-xoma(PMP).AIM To find out if CRS and HIPEC can be used safely and effectively to treat PMP.METHODS This is an observational study.Clinical data of PMP patients treated with CRS+HIPEC at our hospital from January 2013 to June 2023 was collated and analyzed.The main outcome measures were overall survival(OS),and the secondary outcome measures were the incidence of surgical complications and serious adverse events.Complications were graded according to common adverse event evaluation criteria.Peritoneal tumor staging was performed using the peritoneal tumor index(PCI)scoring system,and a cell reduction degree(CCR)score was performed after CRS.CCR-0 and CCR-1 were considered satisfactory CRS.RESULTS A total of 186 patients with PMP were included,with a median age of 56(48-64)years,65(34.9%)years in males,and 121(65.1%)years in females.The median PCI score was 28(20-34)points.The median operative time was 300(211-430)minutes,and no significant complications occurred.91.4%(170/186)were from the appendix,53.2%(99/186)were from the low grade,and 30.6%(57/186)were from the high grade.CCR scores showed that 55 patients(29.6%)achieved satisfactory CRS,and 113 patients(60.8%)did not achieve satisfactory CRS.The fatality rate at 30 days after surgery was 2.7%(5/186),1.6%(3/186)needed a second operation,and the fatality rate at 90 days was 4.3%(8/186).The total incidence of III-IV complications was 43.0%(80/186),among which the higher incidence was mainly anemia(27.4%,51/186),electrolyte disturbance(11.6%,21/181),and albumin decrease(7.5%,14/186).The main compli-cations associated with abdominal surgery were gastrointestinal anastomotic leakage(2.2%,4/186),abdominal hemorrhage(2.2%,4/186),and abdominal infection(4.3%,8/186).The median follow-up was 38.1(95%CI:31.2-45.1)months.The 5-year OS of PMP patients treated with CRS+HIPEC was 50.3%(95%CI:40.7%-59.9%),and the median survival time was 66.1(95%CI:43.1-89.1)months.The results of the survival analysis showed that patients with a low pathological grade,a low PCI,and a satisfactory CCR score had a higher survival rate(all P<0.05).5-year OS was 88.9%(95%CI:68.3%-100.0%)in CCR-0 patients,77.6%(95%CI:62.7%-92.5%)in CCR-1 patients,and 42.0%(95%CI:29.5%-54.5%)in CCR-2/3 patients.CONCLUSION The application of CRS+HIPEC in PMP is safe and feasible,and the survival benefit is high,especially in those who achieve satisfactory CRS,which can significantly extend the OS.

Clinical and demographic features of patients undergoing videocapsule endoscopy management:A descriptive study

BACKGROUND Video-capsule endoscopy(VCE)is an efficient tool that has proven to be highly useful in approaching several gastrointestinal diseases.VCE was implemented in Colombia in 2003,however current characterization of patients undergoing VCE in Colombia is limited,and mainly comes from two investigations conducted before the SARS-CoV-2 pandemic period.AIM To describe the characteristics of patients undergoing VCEs and establish the main indications,findings,technical limitations,and other outstanding features.METHODS A descriptive study was carried out using data from reports of VCE(PillCam SB3 system)use in a Gastroenterology Unit in Bogotá,Colombia between September 2019 and January 2023.Demographic and clinical variables such as indication for the VCE,gastric and small bowel transit times(GTT,SBTT),endoscopic preparation quality,and limitations were described[n(%),median(IQR)].RESULTS A total of 133 VCE reports were analyzed.Most were in men with a median age of 70 years.The majority had good preparation(96.2%),and there were technical limitations in 15.8%of cases.The main indications were unexplained anemia(91%)or occult bleeding(23.3%).The median GTT and SBTT were 14 and 30 minutes,respectively.The frequencies of bleeding stigma(3.79%)and active bleeding(9.09%)were low,and the most frequent abnormal findings were red spots(28.3%),erosions(17.6%),and vascular ectasias(12.5%).CONCLUSION VCE showed high-level safety.The main indication was unexplained anemia.Active bleeding was the most frequent finding.Combined with artificial intelligence,VCE can improve diagnostic precision and targeted therapeutic interventions.

Methodological quality(risk of bias) assessment tools for primary and secondary medical studies: What are they and which is better?

Methodological quality(risk of bias)assessment is an important step before study initiation usage.Therefore,accurately judging study type is the first priority,and the choosing proper tool is also important.In this review,we introduced methodological quality assessment tools for randomized controlled trial(including individual and cluster),animal study,non-randomized interventional studies(including follow-up study,controlled before-and-after study,before-after/pre-post study,uncontrolled longitudinal study,interrupted time series study),cohort study,case-control study,cross-sectional study(including analytical and descriptive),observational case series and case reports,comparative effectiveness research,diagnostic study,health economic evaluation,prediction study(including predictor finding study,prediction model impact study,prognostic prediction model study),qualitative study,outcome measurement instruments(including patient-reported outcome measure development,content validity,structural validity,internal consistency,cross-cultural validity/measurement invariance,reliability,measurement error,criterion validity,hypotheses testing for construct validity,and responsiveness),systematic review and meta-analysis,and clinical practice guideline.The readers of our review can distinguish the types of medical studies and choose appropriate tools.In one word,comprehensively mastering relevant knowledge and implementing more practices are basic requirements for correctly assessing the methodological quality.

Observational Facts Regarding the Joint Activities of the Southwest Vortex and Plateau Vortex after Its Departure from the Tibetan Plateau

Using atmospheric observational data from 1998 to 2013,station rainfall data,TRMM（Tropical Rainfall Measuring Mission） data,as well as annual statistics for the plateau vortex and shear line,the joint activity features of sustained departure plateau vortexes（SDPVs） and southwest vortexes（SWVs） are analyzed.Some new and useful observational facts and understanding are obtained about the joint activities of the two types of vortex.The results show that：（1） The joint active period of the two vortexes is from May to August,and mostly in June and July.（2） The SDPVs of the partnership mainly originate near Zaduo,while the SWVs come from Jiulong.（3） Most of the two vortexes move in almost the same direction,moving eastward together with the low trough.The SDPVs mainly act in the area to the north of the Yangtze River,while the SWVs are situated across the Yangtze River valley.（4） The joint activity of the two vortexes often produces sustained regional heavy rainfall to the south of the Yellow River,influencing wide areas of China,and even as far as the Korean Peninsula,Japan and Vietnam.（5） Most of the two vortexes are baroclinic or cold vortexes,and they both become strengthened in terms of their joint activity.（6） When the two vortexes move over the sea,their central pressure descends and their rainfall increases,especially for SWVs.（7） The two vortexes might spin over the same area simultaneously when there are tropical cyclones in the eastern and southern seas of China,or move southward together if a tropical cyclone appears near Hainan Island.

Endothelial progenitor cells, potential biomarkers for diagnosis and prognosis of ischemic stroke: protocol for an observational case-control study

Ischemic stroke is a devastating,life altering event which can severely reduce patient quality of life.Despite years of research there have been minimal therapeutic advances.Endothelial progenitor cells(EPCs),stem cells involved in both vasculogenesis and angiogenesis,may be a potential therapeutic target.After a stroke,EPCs migrate to the site of ischemic injury to repair cerebrovascular damage,and their numbers and functional capacity may determine patients'outcome.This study aims to determine whether the number of circulating EPCs and their functional aspects may be used as biomarkers to identify the type(cortical or lacunar)and/or severity of ischemic stroke.The study will also investigate if there are any differences in these characteristics between healthy volunteers over and under 65 years of age.100 stroke patients(50 lacunar and 50 cortical strokes)will be recruited in this prospective,observational case-controlled study.Blood samples will be taken from stroke patients at baseline(within 48 hours of stroke)and days 7,30 and90.EPCs will be counted with flow cytometry.The plasma levels of pro-and anti-angiogenic factors and inflammatory cytokines will also be determined.Outgrowth endothelial cells will be cultured to be used in tube formation,migration and proliferation functional assays.Primary outcome is disability or dependence on day 90 after stroke,assessed by the modified Rankin Scale.Secondary outcomes are changes in circulating EPC numbers and/or functional capacity between patient and healthy volunteers,between patient subgroups and between elderly and young healthy volunteers.Recruitment started in February 2017,167 participants have been recruited.Recruitment will end in November 2019.West Midlands-Coventry&Warwickshire Research Ethics Committee approved this study(REC number:16/WM/0304)on September8,2016.Protocol version:2.0.The Bayraktutan Dunhill Medical Trust EPC Study was registered in ClinicalTrials.gov(NCT02980354)on November 15,2016.This study will determine whether the number of EPCs can be used as a prognostic or diagnostic marker for ischemic strokes and is a step towards discovering if transplantation of EPCs may aid patient recovery.

An Observational Study of the 30-50 Day Atmospheric Oscillations Part I: Structure and Propagation

Features of structure and propagation of the 30 to SO day atmospheric oscillations are investigated using the ECMWF analysis of 1980-1983. Evidence is provided to confirm the characteristics of the oscillation in the equatorial region. Those in the mid-high latitudes, however, are revealed to be very different from the tropics and pose a strong barotropic structure. Horizontal coherence shows teleconnection patterns which can be identified as EAP and PNA. The wind field of the specified time scale of the oscillation appears as long-lived vortices and vortex pairs. Mid-latitude perturbations propagate clearly westwards, especially during the winter season. In the high latitudes, they propagate westwards in the winter but eastwards in the summer. Meridional propagations are rather different from region to region.

Observational Study on the Onset of the South China Sea Southwest Monsoon

Based on the long-term marine ship observation data, records of meteorological stations and High-Reflective Cloud(HRC) data by satellite remote sensing , this paper has studied the circulation patterns and variability in elements during onset and the established periods of the South China Sea(SCS) southwest(SW) monsoon. The averaged date of the onset SW monsoon in the SCS occurs in the middle of May climatologically. The corresponding date for the northern part is little earlier (May 12) and those for the southern parts are little later (May 20). The interannual range of the onset dates is about one month. Following the onset of the SW monsoon, the cloud amount and the precipitation increase while the convection activities enhance over the SCS. But there is a strong spatial heterogeneity within the domain. After onset of the SW monsoon the strong convective area moves northwards, while the SCS rain band moves to the center and north. Sea surface temperature(SST) increases rapidly before the onset and the leading time is about one month. The increment of SST supplies heat and vapor for the onset. From April to May the surface heat fluxes display obvious changes, e.g., latent heat exchange and evaporation enhancement. It is one of the reasons why the SW monsoon bursts firstly in the SCS.

An Observational Study of the 30-50 Day Atmospheric Oscillations Part II: Temporal Evolution and Hemispheric Interaction across the Equator

In this part, the temporal evolution and interaction across the equator of 30-50 day oscillation in the atmosphere are investigated further. The annual variation of 30-50 day oscillation is quite obvious in the mid-high latitudes. In the tropical atmosphere, the obvious interannual variation is an important property for temporal evolution of 30-50 day oscillation. The low-frequency wavetrain across the equator over the central Pacific and central Atlantic area, the movement of the long-lived low-frequency system across the equator and the meridional wind component across the equator will obviously show the interaction of 30-50 day oscillation in the atmosphere across the equator.

Outcomes of different minimally invasive surgical treatments for vertebral compression fractures:An observational study

BACKGROUND Osteoporosis with vertebral compression fractures is increasingly common in the elderly population.Cement augmentation is one of the effective surgical treatments for these patients.Currently,there are several different types of cement augmentation treatments.No studies have compared the safety and efficacy of different cement augmentation types for the treatment of such fractures;thus,we retrospectively compared vertebroplasty,balloon kyphoplasty,and kyphoplasty with SpineJack or an intravertebral expandable pillar.AIM To compare the postoperative safety and efficacy of each surgical intervention in treating vertebral compression fractures.METHODS We retrospectively analyzed 354 patients with acute vertebral compression fractures,defined as signal changes in the T1 weighted magnetic resonance imaging,and randomly divided the patients into five groups.Their visual analog scale scores for pain,kyphotic angle,average body height,rate of cement leakage,and occurrence of adjacent vertebral compression fractures were followed for 1 year.One-way analysis of variance,the post hoc Bonferroni test,and Fisher exact probability test were used for statistical analyses.RESULTS All pain scores significantly improved 12 mo postoperatively;however,there was no significant difference between the groups(P=0.325).Kyphoplasty with SpineJack significantly reduced the kyphotic angle(P=0.028)and restored the height of the vertebral body(P=0.02).The rate of adjacent compression fractures was the highest in the vertebroplasty group,with a statistically significant difference according to the Fisher exact probability test(P=0.02).The treatment with the lowest cement leakage rate cannot be identified because of the small sample size;however,kyphoplasty with SpineJack,an IVEP,and vesselplasty resulted in lower rates of cement leakage than balloon kyphoplasty and vertebroplasty.CONCLUSION Kyphoplasty with SpineJack has good outcomes in kyphotic angle reduction and body height restoration.Vertebroplasty has the highest cement leakage rate and adjacent compression fracture occurrence.

The Relationships between Erythrocyte Membrane n-6 to n-3 Polyunsaturated Fatty Acids Ratio and Blood Lipids and C-reactive Protein in Chinese Adults:An Observational Study

Objective To investigate the relationships between erythrocyte membrane n-6：n-3 PUFAs ratio and blood lipids and high sensitivity C-reactive protein （hs-CRP）. Methods The Chinese and a observational study consisted of a population-based cross-sectiona subsequent 1-year follow-up study of 171 subjects with the fasting cholesterol of 5.13-8.00 mmol/L. study of 456 plasma total Results In the cross-sectional analysis, plasma low-density lipoprotein cholesterol （LDL-c） had a significant and negative association with the erythrocyte membrane n-6：n-3 PUFAs ratio （P for trend=0.019） after adjusting for sex, age and total PUFA percentage. In the follow-up study, 171 subjects were categorized into quartiles by the changes of n-6：n-3 ratio in erythrocyte membrane （△=month 12-month 0）. In the top quartile whose ratios of n-6：n-3 increased by an average of 1.25 during the follow-up, the LDL-c-lowering extent was 3.3 times of that in the lowest quartile whose ratios of n-6：n-3 decreased by an average of 1.13 （-1.07 mmol/L v.s. -0.32 mmol/L）. The hsCRP decreased by 0.11 mg/dL in the lowest quartile while increasing by 0.10 mg/dL in the top quartile （P for difference=0.052）. Conclusion Our results suggested that the balance between n-6 and n-3 fatty acids may optimize the cardiovascular benefits from dietary PUFAs.

Sensorineural hearing dysfunction after discharge from critical care in adults:A retrospective observational study

Background Patients undergoing intensive care are exposed to risk factors for hearing impairment.This study assessed the worse changes in pure tone average(PTA)thresholds after intensive care and identified the factors associated with worse hearing function.Methods We conducted a single-centre retrospective study,and included adult patients admitted to the intensive care unit(ICU)of Kurashiki Central Hospital between January 2014 and September 2019,who had regular pure tone audiometry performed before and after ICU admission.Correlations between changes in PTA threshold and patient characteristics,were evaluated.The included ears were classified as those with worse hearing(>10 dB increase in the PTA threshold)and those without worse hearing,and the baseline characteristics were compared.Results During the study period,125 ears of 71 patients(male:female ratio,35:36;mean age,72.5±12.3 years)met the eligibility criteria.Age,sex,and the use of furosemide were not correlated with changes in PTA threshold.Univariate analysis showed that ears with worse hearing were associated with a lower serum platelet count than ears without worse hearing(153±85×10^(9)/L vs.206±85×10^(9)/L,respectively;P=0.010),and the rate of planned ICU admission(elective surgery)was higher in the worse hearing group(57.1% vs.28.8%,respectively;p=0.011).Conclusions Age,sex,and the use of furosemide did not have adversely affect hearing function.Low serum platelet count and planned admission appear to be risk factors for worse hearing.

Comment on “Outcomes of different minimally invasive surgical treatments for vertebral compression fractures: An observational study”

Recently we read the article entitled“Outcomes of different minimally invasive surgical treatments for vertebral compression fractures:An observational study”.This was an observational study that reviewed the safety and efficacy of different cement augmentation modalities for vertebral compression fractures under osteoporotic condition.Overall,this is a valuable study that can provide a reference for clinical practice.On the other hand,we also noticed some points in the article and are willing to share our views.Further studies with a higher level of evidence can add more knowledge regarding relevant concerns.

Prescription of Cancer Treatment Modalities in Developing Countries:Results from a Multi-Centre Observational Study

Background: Treatment is an important component of a comprehensive cancer control approach and its outcomes strongly depend on infrastructure, equipment, human and financial resources available. Therefore it is imperative to generate evidence-based tools to assist health policy makers from low resourced countries in planning efficient and equitable treatment services for a defined population based on what it is feasible to these settings. Methods: The intended cancer spe-cific treatment planned and written in the patients’ medical record (treatment prescription) of untreated adult cancer cases (≥18 years of age), excluding non-melanoma skin cancer, was recorded in a chronological way from 1 January 2012 onwards in a group of eight comprehensive cancer centres located in middle income countries and offering the main modalities of cancer treatment (surgery, medical oncology and radiotherapy). Results: A total of 17,713 medical records were reviewed, of which 7106 (54.2%) met the eligibility criteria. Prescription of main cancer treatment modalities were distributed as follows: 57.6% for chemotherapy (n = 4093), 56.8% for surgery (n = 4038), and 46.8% for radiotherapy (n = 3327). There was a predominance of plans consisting of combined treatment modalities over monotherapy (55.2% versus 44.8%). At the time of diagnosis 54.3% of the cancer cases had disease that had spread beyond the primary site, 41.2% were considered as having local disease and in 4.5% of the cases the information on disease extension was unknown. Conclusions: The results obtained should be seen as an approximation of cancer treatment service demand based on what it is currently practiced and therefore feasible in developing countries, particularly in middle income countries.