Deciphering Cathepsin K inhibitors: a combined QSAR, docking and MD simulation based machine learning approaches for drug design.

Cathepsin K (CatK), a lysosomal cysteine protease, contributes to skeletal abnormalities, heart diseases, lung inflammation, and central nervous system and immune disorders. Currently, CatK inhibitors are associated with severe adverse effects, therefore limiting their clinical utility. This study focuses on exploring quantitative structure-activity relationships (QSAR) on a dataset of CatK inhibitors (1804) compiled from the ChEMBL database to predict the inhibitory activities. After data cleaning and pre-processing, a total of 1568 structures were selected for exploratory data analysis which revealed physicochemical properties, distributions and statistical significance between the two groups of inhibitors. PubChem fingerprinting with 11 different machine-learning classification models was computed. The comparative analysis showed the ET model performed well with accuracy values for the training set (0.999), cross-validation (0.970) and test set (0.977) in line with OECD guidelines. Moreover, to gain structural insights on the origin of CatK inhibition, 15 diverse molecules were selected for molecular docking. The CatK inhibitors (1 and 2) exhibited strong binding energies of -8.3 and -7.2 kcal/mol, respectively. MD simulation (300 ns) showed strong structural stability, flexibility and interactions in selected complexes. This synergy between QSAR, docking, MD simulation and machine learning models strengthen our evidence for developing novel and resilient CatK inhibitors.

Measurement of Angular Coefficients of B[over ¯]→D

We measure the complete set of angular coefficients J_{i} for exclusive B[over ¯]→D^{*}ℓν[over ¯]_{ℓ} decays (ℓ=e, µ). Our analysis uses the full 711 fb^{-1} Belle dataset with hadronic tag-side reconstruction. The results allow us to extract the form factors describing the B[over ¯]→D^{*} transition and the Cabibbo-Kobayashi-Maskawa matrix element |V_{cb}|. Using recent lattice QCD calculations for the hadronic form factors, we find |V_{cb}|=(40.7±0.7)×10^{-3} using the Boyd-Grinstein-Lebed parametrization, compatible with determinations from inclusive semileptonic decays. We search for lepton flavor universality violation as a function of the hadronic recoil parameter w and investigate the differences of the electron and muon angular distributions. We find no deviation from standard model expectations.

Measurements of the Branching Fraction, Polarization, and CP Asymmetry for the Decay B

We present a comprehensive study of B^{0}→ωω decays using 772×10^{6} BB[over ¯] pairs collected with the Belle detector at the KEKB e^{+}e^{-} collider. This process is a suppressed charmless decay into two vector mesons and can exhibit interesting polarization and CP violation. The decay is observed for the first time with a significance of 7.9 standard deviations. We measure a branching fraction B=(1.53±0.29±0.17)×10^{-6}, a fraction of longitudinal polarization f_{L}=0.87±0.13±0.13, and a time-integrated CP asymmetry A_{CP}=-0.44±0.43±0.11, where the first uncertainties listed are statistical and the second are systematic. This is the first observation of B^{0}→ωω and the first measurements of f_{L} and A_{CP} for this decay.

Nationwide precision oncology pilot study: KOrean Precision Medicine Networking Group Study of MOlecular profiling-guided therapy based on genomic alterations in advanced solid tumors (KOSMOS) KCSG AL-20-05.

BACKGROUND: Next-generation sequencing (NGS) has become widely available but molecular profiling-guided therapy (MGT) had not been well established in the real world due to lack of available therapies and expertise to match treatment. Our study was designed to test the feasibility of a nationwide platform of NGS-guided MGT recommended by a central molecular tumor board (cMTB) for metastatic solid tumors. PATIENTS AND METHODS: Patients with advanced or metastatic solid tumors with available NGS results and without standard treatment were enrolled. The cMTB interpreted the patients' NGS reports and recommended the following: (i) investigational medicinal products (IMPs) approved in other indications; (ii) alternative treatments; (iii) clinical trials. The primary variables were the proportion of patients with actionable genomic alterations and those receiving MGT as per cMTB recommendations. Others included treatment duration (TD), overall response rate (ORR), disease control rate (DCR), and safety. RESULTS: From February 2021 to February 2022, 193 cases [99 (51.3%) men; median age 58 years (range 24-88 years); median line of previous treatment 3 (range 0-9)] from 29 sites were enrolled for 60 cMTB sessions. The median time from case submission to cMTB discussion was 7 days (range 2-20 days), and to IMP treatment initiation was 28 days (range 14-90 days). Actionable genetic alterations were found in 145 patients (75.1%). A total of 89 (46.1%) patients received actual dosing of IMPs, and 10 (5.2%) were enrolled in cMTB-recommended clinical trials, achieving an MGT rate of 51.3%. ORR and DCR of IMPs were 10.1% and 72.5%, respectively. The median TD was 3.5 months [95% confidence interval (CI) 2.8-5.5 months], and the 4-month TD rate was 44.9%. The median overall survival of patients who received IMPs was 6.9 months (95% CI 5.2-10.0 months). CONCLUSION: KOSMOS confirmed the feasibility of MGT recommended by the cMTB, achieving a high MGT match rate and promising effectiveness in heavily pretreated advanced cancer patients.

A phase II study of tepotinib in patients with advanced solid cancers harboring MET exon 14 skipping mutations or amplification (KCSG AL19-17).

BACKGROUND: We evaluated the efficacy and safety of tepotinib in patients with various solid cancers harboring MET exon 14 skipping mutation (METex14) or MET gene amplification. PATIENTS AND METHODS: A phase II, multicenter study was conducted in patients with advanced or metastatic solid cancers who progressed after standard treatment, harboring either METex14 or MET amplification detected in tissue-based next-generation sequencing (NGS). The primary endpoint was objective response rate (ORR). For exploratory analyses, we analyzed the gene profiles using plasma NGS test. RESULTS: Thirty-five patients were enrolled. The ORR was 57.6% for all patients, 52.2% for those with METex14, and 70% for those with MET amplification. Median progression-free survival (PFS) was 8 months [95% confidence interval (CI) 4.5-11.5 months] and median overall survival (OS) was 14 months (95% CI 7.8-20.2 months) in all patients. For patients with non-small-cell lung cancer with METex14, the median PFS was 9 months (95% CI 4.7-13.4 months) and the median OS was 17 months [95% CI not applicable (NA)-NA]. For patients with MET amplification, the median PFS was 7 months (95% CI 1.5-12.5 months) and the median OS was 10 months (95% CI 5.8-14.2 months). The ORR of patients with MET dysregulation detected by plasma NGS was 72.2%, whereas the ORR was 30% in those without detection. The most common adverse events were peripheral edema, asthenia, transaminase elevation, and anorexia, mostly grade 1 or 2. CONCLUSIONS: Tepotinib demonstrated consistent antitumor activity in patients with METex14, and promising antitumor activity in various cancers with MET amplification. Detection of MET dysregulation by plasma NGS may predict the response to tepotinib.

Exposome Signatures of Gastrointestinal Disorders Among Active Duty Service Members.

INTRODUCTION: We evaluated the risk factors associated with gastrointestinal disorders (GD) among the soldiers of the Army and Marine Aviation community (AMAC) using an exposomic approach. Specifically, we aimed to determine the medical and operational factors associated with reported GD in the Military Health System. METHODS: Longitudinal data were obtained from the Medical Assessment and Readiness System (MARS) housed at Womack Army Medical Center, Fort Liberty, NC, for a retrospective cohort study that included 79,249 active duty United States AMAC active duty service members (ADSMs) from October 2015 to December 2019. Multivariable mixed-effects logistic regression was used to assess the relationship between the incidence occurrence of GD and variables including rank, service time, deployment, Armed Forces Qualification Test score, education, tobacco use, alcohol use, age, gender, race, ethnicity, body mass index (BMI), and marital status. RESULTS: The incidence of GD included 22,813 person-years of observations with a rate of 2.2 per 100 person-years and a period prevalence of 3.2%. GD was independently associated with rank, service time, and deployment (all P < 0.05). CONCLUSION: The high-risk categories associated with GD in the AMAC included age, BMI, race (not ethnicity), marital status, and service time. Our data also show that deployment time, not geographical location, was associated with a higher risk of GD. Together, these analyses suggest that White ADSMs older than 33 years of age who have experienced marriage, longer service time, and deployments appear to have a higher risk of GDs. Our assessment shows the utility of using an exposomic approach to create a member-specific, big data-informed personalized clinical algorithm of health outcomes.

Fasciotomy and Occupational Separation among US Service Members with Lower Extremity Chronic Exertional Compartment Syndrome.

PURPOSE: Lower extremity chronic exertional compartment syndrome (LE-CECS) can limit rigorous physical activity, particularly in the US military, and fasciotomy is a potential treatment. Associations between LE-CECS, fasciotomy, and occupational outcomes appear understudied. We studied active-duty US service members to identify whether LE-CECS diagnoses and fasciotomy for LE-CECS predict military service separation. METHODS: We conducted a retrospective cohort study of 1,103,417 individuals who entered service during 2011 to 2017. Distributions of separation statuses and independent variables were tabulated, and sex-specific multivariable regression models were computed for separation outcomes. RESULTS: LE-CECS was associated with a 474% medical service separation risk in men (95% confidence interval (CI) for adjusted risk ratio: 5.21 to 6.33) and a 282% increase in women (CI: 2.99 to 4.88). Among 1947 patients with LE-CECS, men saw a 57% nonmedical separation risk increase (CI: 1.27 to 1.93) and women had a 119% increase (CI: 1.10 to 4.35) when anterior and/or lateral compartment procedures occurred. Men with LE-CECS and any posterior procedures saw a 47% nonmedical separation risk increase (CI: 1.17 to 1.86). Men with anterior and/or lateral procedures and any posterior procedures experienced 36% (CI: 1.09 to 1.71) and 78% (CI: 1.40 to 2.26) medical separation risk increases, respectively. No statistically significant risk increases for the outcomes were otherwise seen for women. CONCLUSIONS: LE-CECS was associated with increased military service discharge risks. Among the affected patients, positive effects on career longevity were not seen in association with fasciotomy. However, fasciotomy could simply serve as a marker of the most refractory cases that are least likely to continue service. More study is needed to clarify causal pathways and identify patients who may derive career benefits from surgical treatment.

The GRB221009A gamma-ray burst as revealed by the gamma-ray spectrometer onboard the KPLO (Danuri).

The strongest gamma-ray burst (GRB) of the century, GRB20221009A, has been detected by the Korean Pathfinder Lunar Orbiter Gamma-ray Spectrometer (KGRS) instrument onboard the Korean Pathfinder Lunar Orbiter (KPLO). KGRS uses a LaBr3 detector to measure GRB counts with five energy bins in the energy range from 30 keV to 12 MeV. KGRS detected GRB221009A at a distance of 1.508 million kilometers from the Earth. The full duration of the main burst was recorded between 13:20 and 13:26 on October 9, 2022 with peak counts of over 1000 times background. The dead time of KGRS reached as high as 50%, and the intrinsic gamma-ray spectrum of LaBr3 was significantly altered.

Single host plant species may harbour more than one species of Peronospora - a case study on Peronospora infecting Plantago.

The genus Peronospora is the largest genus of the oomycetes, fungus-like members of the kingdom Straminipila that also contains amoeboid (e.g., Leukarachnion) and plant-like (e.g., Laminaria) lifeforms. Peronospora species are obligate biotrophic plant pathogens, causing high economic losses in various crops and ornamentals, including Plantago species. Several species of Plantago are used as speciality crops and medicinal plants. In this study, Peronospora species parasitic on Plantago were investigated based on morphology and phylogenetic analyses using two nuclear (ITS, nrLSU) loci and one mitochondrial (cox2) locus. As a result of these investigations, 10 new species are added to the already known Peronospora species on Plantago. Interestingly, it was found that four independent species are parasitic to Plantago major, highlighting that the reliance on the host plant for pathogen determination can be misleading in Peronospora. Taking this into account, morphological and phylogenetic analyses should be conducted as a prerequisite for effective quarantine regulations and phytosanitary measures. Citation: Mu M, Choi Y-J, Kruse J, et al. 2024. Single host plant species may harbour more than one species of Peronospora - a case study on Peronospora infecting Plantago. Persoonia 52: 94-118. https://doi.org/10.3767/persoonia.2024.52.04 .

Tick-borne pathogens isolated from ticks, rodents, and a shrew in Gangwon and Gyeonggi provinces in the Republic of Korea.

The prevalence of tick-borne pathogens (TBP), Orientia tsutsugamushi, Rickettsia and Borrelia spp. in wild small animals, namely wild rodents, is now widely investigated. This study is to present the prevalence and distribution of O. tsutsugamushi, Rickettsia and Borrelia spp. in wild small animals and ticks collected from Gyeonggi and Gangwon provinces, Republic of Korea (ROK) in 2014. A total of 131 wild small animals, rodents and shrews, and 2,954 ticks were collected from Gyeonggi and Gangwon provinces from May to November 2014. The wild small animals (KR1-9) and ticks (K1-17) were grouped in accordance with capture dates and locations. Among the wild small animals, a total of 393 tissues and blood samples were extracted from six selected small animal series (KR1-3, KR6-8). Also, each date and location-grouped ticks were identified for its species and pooled according to the stage of development. Molecular identification for Rickettsia, Orientia, and Borrelia species was performed using polymerase chain reaction (PCR). To detect TBPs among wild small animals and ticks, primer sets targeting the 56 kDa protein encoding gene of Orientia spp., outer membrane protein B gene (OmpB) of Rickettsia spp., and 5S-23S intergenic spacer region (IGS) gene of Borrelia spp. were used. Of the 393 wild small animals' blood and tissue samples, 199 (50.6%) were positive for Orientia spp., 158 (40.2%) were positive for Borrelia spp., and 55 (14.0%) were positive for Rickettsia spp. Moreover, a total of 14 tick pools (n = 377) was positive for Rickettsia spp. (n=128, 34.0%) and Borrelia spp. (n=33, 8.8%). High prevalence of Orientia spp. and Rickettsia spp. in rodents and shrews were observed. This study presents significant insights by presenting data collected in 2014 that the prevalence of TBP was already high in mid 2010s. This study highlights the sustainable routine surveillance model for TBP.

The impact of resilience and coping strategies on depressive symptoms among Korean American older adults during COVID-19.

OBJECTIVES: This study examined how resilience and coping strategies were associated with depressive symptoms among Korean American older adults during COVID-19. The prevalent depressive symptoms and low use of mental health services in this population have raised significant concerns among healthcare professionals. Therefore, this study aims to understand the relationships between resilience and coping types on depressive symptoms and provide valuable insights into addressing these issues within this ethnic group. METHOD: A cross-sectional survey was conducted with 132 Korean American older adults. Hierarchical linear regression analyses were performed to assess the effect of sociodemographic factors (age, gender, marital status, years of living in the U.S., self-rated health, financial security), resilience, and coping strategies (problem-focused coping, emotion-focused coping, avoidant coping) on depressive symptoms. Next, the interactions between resilience and three coping strategies for depressive symptoms were tested. RESULTS: The findings show that depressive symptoms were associated with financial security and avoidant coping. Also, resilience interacted with avoidant coping and emotion-focused coping. Among the participants with low resilience, depressive symptoms increased rapidly when avoidant and emotion-focused coping strategies increased, respectively. CONCLUSION: This study emphasizes the importance of culturally tailored interventions to promote resilience and decrease avoidant and emotion-focused coping among Korean American older adults.

Search for Baryon-Number-Violating Processes in B

We report the results of the first search for B^{-} decays to the Ξ[over ¯]_{c}^{0}Λ[over ¯]_{c}^{-} final state using 711 fb^{-1} of data collected at the ϒ(4S) resonance with the Belle detector at the KEKB asymmetric-energy e^{+}e^{-} collider. The results are interpreted in terms of both direct baryon-number-violating B^{-} decay and Ξ_{c}^{0}-Ξ[over ¯]_{c}^{0} oscillations which follow the standard model decay B^{-}→Ξ_{c}^{0}Λ[over ¯]_{c}^{-}. We observe no evidence for baryon number violation and set the 95% confidence-level upper limits on the ratio of baryon-number-violating and standard model branching fractions B(B^{-}→Ξ[over ¯]_{c}^{0}Λ[over ¯]_{c}^{-})/B(B^{-}→Ξ_{c}^{0}Λ[over ¯]_{c}^{-}) to be <2.7% and on the effective angular frequency of mixing ω in Ξ_{c}^{0}-Ξ[over ¯]_{c}^{0} oscillations to be <0.76 ps^{-1} (equivalent to τ_{mix}>1.3 ps).

STING recognition of viral dsDNA by nociceptors mediates pain in mice.

Pain is often one of the initial indicators of a viral infection, yet our understanding of how viruses induce pain is limited. Immune cells typically recognize viral nucleic acids, which activate viral receptors and signaling, leading to immunity. Interestingly, these viral receptors and signals are also present in nociceptors and are associated with pain. Here, we investigate the response of nociceptors to nucleic acids during viral infections, specifically focusing on the role of the viral signal, Stimulator of Interferon Genes (STING). Our research shows that cytosolic double-stranded DNA (dsDNA) from viruses, like herpes simplex virus 1 (HSV-1), triggers pain responses through STING expression in nociceptors. In addition, STING agonists alone can elicit pain responses. Notably, these responses involve the direct activation of STING in nociceptors through TRPV1. We also provided a proof-of-concept showing that STING and TRPV1 significantly contribute to the mechanical hypersensitivity induced by HSV-1 infection. These findings suggest that STING could be a potential therapeutic target for relieving pain during viral infections.

The interplay of social support and education on diabetes knowledge: a focus on Korean American women.

OBJECTIVE: Although diabetes is one of the leading causes of death among Korean Americans, the levels and predictors of diabetes knowledge in this group have not been sufficiently reported. This study aimed to (1) describe the level of diabetes knowledge of Korean immigrant women in the U.S. and (2) examine whether there is an interaction effect between social support and education on diabetes knowledge. DESIGN: This study conducted a cross-sectional survey design. The sample included 227 Korean immigrant women living in the southeast region of the U.S. The fourteen items of the Diabetes Knowledge Test were used to assess the diabetes knowledge level of Korean American women. A multiple linear regression analysis was conducted to examine the interaction effect between social support and education on diabetes knowledge. RESULTS: Only 6% of the participants presented a good diabetes knowledge level, 12.5% had a poor level, and the majority (81.5%) had a moderate level. We found a significant interaction effect between social support and education on diabetes knowledge. The highest diabetes knowledge was observed when individuals with a lower education level had higher social support. CONCLUSION: Future health practices and policies may focus on increasing knowledge among Korean American women with lower education levels and lower social support. Implementing peer-led initiatives can enhance diabetes knowledge and encourage better self-care practices within the community.

Metataxonomic and metabolomic profiling revealed Pinus koraiensis cone essential oil reduced methane emission through affecting ruminal microbial interactions and host-microbial metabolism.

BACKGROUND: Pinus koraiensis cone essential oil (PEO) contains functional compounds such as monoterpene hydrocarbons, and the administration of PEO reduced methane (CH4) emissions during growing phase of goats. However, the mode of action of PEO driven CH4 reduction is not known, especially how the administration of PEO can affect rumen microbiota and host metabolism in goats during the fattening phase. This study aimed to elucidate the potential microbial and host responses PEO supplementation in goats using metataxonomics (prokaryotes and protozoa) and metabolomics (rumen fluid and serum). RESULTS: Ten fattening Korean native goats were divided into two dietary groups: control (CON; basal diet without additives) and PEO (basal diet + 1.5 g/d of PEO) with a 2 × 2 crossover design and the treatment lasted for 11 weeks. Administration of PEO reduced CH4 concentrations in the exhaled gas from eructation by 12.0-13.6% (P < 0.05). Although the microbial composition of prokaryotes (bacteria and archaea) and protozoa in the rumen was not altered after PEO administration. MaAsLin2 analysis revealed that the abundance of Selenomonas, Christensenellaceae R-7 group, and Anaerovibrio were enriched in the rumen of PEO supplemented goats (Q < 0.1). Co-occurrence network analysis revealed that Lachnospiraceae AC2044 group and Anaerovibrio were the keystone taxa in the CON and PEO groups, respectively. Methane metabolism (P < 0.05) was enriched in the CON group, whereas metabolism of sulfur (P < 0.001) and propionate (P < 0.1) were enriched in the PEO group based on microbial predicted functions. After PEO administration, the abundance of 11 rumen and 4 serum metabolites increased, whereas that of 25 rumen and 14 serum metabolites decreased (P < 0.1). Random forest analysis identified eight ruminal metabolites that were altered after PEO administration, among which four were associated with propionate production, with predictive accuracy ranging from 0.75 to 0.88. Additionally, we found that serum sarcosine (serum metabolite) was positively correlated with CH4 emission parameters and abundance of Methanobrevibacter in the rumen (|r|≥ 0.5, P < 0.05). CONCLUSIONS: This study revealed that PEO administration reduced CH4 emission from of fattening goats with altered microbial interactions and metabolites in the rumen and host. Importantly, PEO administration affected utilizes various mechanisms such as formate, sulfur, methylated amines metabolism, and propionate production, collectively leading to CH4 reduction. The knowledge is important for future management strategies to maintain animal production and health while mitigate CH4 emission.

Assessment of a continuous passive motion assistive device in dogs following stifle surgery.

Canine rehabilitation optimizes recovery and the quality of life in dogs with musculoskeletal conditions or after surgery. Achieving proper range of motion (ROM) is vital post-stifle surgery, often accomplished through manual therapy and active exercises. We investigated the mechanical performance of a continuous passive motion (CPM) device for dogs and its potential use in canine rehabilitation therapy. In the ethical review process, our research was accepted to be evaluated in a sample of four dogs that had undergone left stifle surgery. Each dog underwent four sessions with the device at three different speeds. Results showed the device replicated extension angles close to goniometer measurements used in manual therapy. Flexion was also achieved, but not to the same extent. A force threshold stopped the device, avoiding discomfort in dogs with restricted ROM. Dog-specific factors like body position, opposition to movement, limb size, stage of recovery, haircoat, and discomfort, appeared to influence device operation. Mechanical improvements to allow for enhanced flexion are recommended in future CPM device designs, including a resistance threshold that could be adjusted for individual dogs and stages of healing. This study serves as a foundation for future advancements in canine rehabilitation systems. A canine CPM device may provide an affordable option to improve ROM. This could be beneficial for dog owners, who may not be comfortable with manual therapy, to assist with home rehabilitation exercises.

Antenatal creatine supplementation reduces persistent fetal lung inflammation and oxidative stress in an ovine model of chorioamnionitis.

Chorioamnionitis is a common antecedent of preterm birth and induces inflammation and oxidative stress in the fetal lungs. Reducing inflammation and oxidative stress in the fetal lungs may improve respiratory outcomes in preterm infants. Creatine is an organic acid with known anti-inflammatory and antioxidant properties. The objective of the study was to evaluate the efficacy of direct fetal creatine supplementation to reduce inflammation and oxidative stress in fetal lungs arising from an in utero proinflammatory stimulus. Fetal lambs (n = 51) were instrumented at 90 days gestation to receive a continuous infusion of creatine monohydrate (6 mg·kg-1·h-1) or saline for 17 days. Maternal chorioamnionitis was induced with intra-amniotic lipopolysaccharide (LPS; 1 mg, O55:H6) or saline 7 days before delivery at 110 days gestation. Tissue creatine content was assessed with capillary electrophoresis, and inflammatory markers were analyzed with Luminex Magpix and immunohistochemistry. Oxidative stress was measured as the level of protein thiol oxidation. The effects of LPS and creatine were analyzed using a two-way ANOVA. Fetal creatine supplementation increased lung creatine content by 149% (PCr < 0.0001) and had no adverse effects on lung morphology. LPS-exposed groups showed increased levels of interleukin-8 in the bronchoalveolar lavage (PLPS < 0.0001) and increased levels of CD45+ leukocytes (PLPS < 0.0001) and MPO+ (PLPS < 0.0001) cells in the lung parenchyma. Creatine supplementation significantly reduced the levels of CD45+ (PCr = 0.045) and MPO+ cells (PCr = 0.012) in the lungs and reduced thiol oxidation in plasma (PCr < 0.01) and lung tissue (PCr = 0.02). In conclusion, fetal creatine supplementation reduced markers of inflammation and oxidative stress in the fetal lungs arising from chorioamnionitis.NEW & NOTEWORTHY We evaluated the effect of antenatal creatine supplementation to reduce pulmonary inflammation and oxidative stress in the fetal lamb lungs arising from lipopolysaccharide (LPS)-induced chorioamnionitis. Fetal creatine supplementation increased lung creatine content and had no adverse effects on systemic fetal physiology and overall lung architecture. Importantly, fetuses that received creatine had significantly lower levels of inflammation and oxidative stress in the lungs, suggesting an anti-inflammatory and antioxidant benefit of creatine.

Non-cardiac comorbid health outcomes and prevalence after myocardial infarction: an umbrella review.

OBJECTIVE: There exists limited comprehensive evidence on the potential association between non-cardiac comorbidities and myocardial infarction (MI). Thus, we conducted an umbrella review of existing meta-analyses to provide a broad understanding of non-cardiac health outcomes associated with MI. MATERIALS AND METHODS: The primary focus on the prevalence of related health outcomes in patients with MI was systemically searched. Each original meta-analysis that was included had its methodological quality evaluated by a Measurement Tool Assessment Systematic Reviews 2 (AMSTAR2). To evaluate the certainty in the evidence for each outcome, we employed GRADE and the Joanna Briggs Institute Prevalence Critical Appraisal Tool. The protocol was registered in PROSPERO (CRD42023458642). RESULTS: We identified seven meta-analyses comprising 126 studies with 336,581 participants from 22 countries and five continents. The pooled prevalence of comorbidities in patients with MI was 39% anxiety [95% confidence interval (CI), 30-48; GRADE, very low certainty], 29% depression (95% CI, 23-36; very low certainty), 39% frailty (95% CI, 24-55; very low certainty), and 23% failure of returning to work (95% CI, 16-29; very low certainty). The diagnosis of MI was associated with an increased risk of cognitive impairment (odds ratio, 1.45; 95% CI, 1.10-1.92; moderate certainty). Among frail patients, MI was associated with an increased risk of major bleeding (relative risk, 1.93; 95% CI, 1.08-3.45; low certainty) and mortality (relative risk, 2.29; 95% CI, 1.48-3.53; moderate certainty). However, we did not find any evidence of cancer risk associated with the development of MI. CONCLUSIONS: Our umbrella meta-analysis provided comprehensive evidence of the association between MI and several non-cardiac health conditions. The robustness of our study is attributed to the integration of evidence across several studies, thus, these insights offer valuable treatment options for policymakers and physicians to develop personalized health strategies.