Journal of Internal Medicine最新文献

{"title":"Tadalafil use is associated with a lower incidence of Type 2 diabetes in men with benign prostatic hyperplasia: A population-based cohort study","authors":"Atsushi Takayama,&nbsp;Satomi Yoshida,&nbsp;Koji Kawakami","doi":"10.1111/joim.20012","DOIUrl":"10.1111/joim.20012","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Tadalafil, commonly prescribed for benign prostatic hyperplasia (BPH), may benefit patients with Type 2 diabetes mellitus (T2DM) for glycemic markers and complications. However, the association between the long-term use of tadalafil and the incidence of T2DM has not been investigated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We emulated a target trial of tadalafil use (5 mg/day) and the risk of T2DM using a population-based claims database in Japan. Patients who initiated tadalafil or alpha-blockers for BPH and had no history of diabetes diagnosis, no dispensing of glucose-lowering drugs, and no history of hemoglobin A1c levels of ≥6.5% (47–48 mmol/mol) were included. The primary outcome was the incidence of T2DM. Pooled logistic regression was used to estimate adjusted risk ratios (RRs) and 5-year cumulative incidence differences (CIDs).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 5180 participants initiated tadalafil treatment and were compared with 20,049 patients who initiated alpha-blockers. The median follow-up time for each arm was 27.2 months (interquartile range [IQR], 12.0–47.9) in tadalafil users and 31.3 months (IQR, 13.7–57.2) in alpha-blocker users. The incidence rates of T2DM in tadalafil and alpha-blocker users were 5.4 (95% confidence interval [CI], 4.0–7.2) and 8.8 (95% CI, 7.8–9.8) per 1000-person years, respectively. Initiation of tadalafil was associated with a reduced risk of T2DM (RR, 0.47; 95% CI, 0.39–0.62; 5-year CID, −0.031; 95% CI, −0.040 to −0.019).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The incidence of T2DM was lower in men with BPH treated with tadalafil than in those treated with alpha-blockers. Thus, tadalafil may be more beneficial than alpha-blockers in preventing T2DM.</p>\u0000 </section>\u0000 </div>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"296 5","pages":"422-434"},"PeriodicalIF":9.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.20012","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142254081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Authors reply: Adherence to guideline-recommended care of late-onset hypertension in females versus males: A population-based cohort study","authors":"Ann Bugeja,&nbsp;Gregory L. Hundemer,&nbsp;Daniel I. McIsaac","doi":"10.1111/joim.20010","DOIUrl":"10.1111/joim.20010","url":null,"abstract":"&lt;p&gt;Dear Editor,&lt;/p&gt;&lt;p&gt;We thank Dr. Huang et al. for their thoughtful response to our published manuscript [&lt;span&gt;1, 2&lt;/span&gt;]. Their first concern addresses our interpretation of the adjusted hazard ratio (aHR 0.98 [95% CI 0.96, 0.99]) for antihypertensive medication prescription by sex. Although statistically significant, its clinical significance remains uncertain, though we acknowledge its relevance at the population level in the discussion section of our manuscript. To explore potential effect modifiers, we tested a priori interactions between sex and several plausible variables—age, diabetes status, era of hypertension diagnosis, and preexisting cardiovascular disease—by incorporating these multiplicative terms into our model. We then reported aHRs of each stratum from stratified analyses for those variables that were statistically significant on the multiplicative scale. However, we did not report measures of relative excess due to interaction [&lt;span&gt;3&lt;/span&gt;]. It is certainly possible that other covariates may have been effect modifiers of the association between sex and prescription of antihypertensive medication.&lt;/p&gt;&lt;p&gt;Second, misclassification bias is a recognized issue in observational studies utilizing administrative data. Nonetheless, the case definition for hypertension used in our study has been validated, showing a sensitivity of 75%, specificity of 94%, positive predictive value of 81%, and negative predictive value of 92%, as detailed in our methods section [&lt;span&gt;4&lt;/span&gt;]. As the authors correctly note, administrative data do not capture nuances related to gender and patient preferences that can influence hypertension treatment, which may introduce residual confounding [&lt;span&gt;5&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Third, although the aHR for the prescription of guideline-recommended antihypertensive medication is statistically significant (aHR 0.995, 95% CI [0.994, 0.997]), determining its clinical significance is challenging. We acknowledge that this effect may be clinically relevant at the population level, as discussed in our manuscript. Evaluating antihypertensive medication prescriptions over time, alongside data on actual blood pressure management and drug intolerance, would offer additional insights beyond our current findings.&lt;/p&gt;&lt;p&gt;Lastly, we aimed to address the observation that better cardiovascular outcomes in females compared to males do not appear to be linked to the completion of hypertension-related investigations or the prescription of antihypertensive medication [&lt;span&gt;6&lt;/span&gt;]. We proposed that females might benefit more from antihypertensive treatment compared to males, but we recognize that we cannot draw definitive conclusions due to limitations such as insufficient data on treatment adherence, gender-specific issues, and potential residual confounding. More detailed data would enhance our study and support the development of targeted implementation strategies for older populations.&lt;/p&gt;&lt;p&gt;The authors declare no conflicts of i","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"296 5","pages":"454-455"},"PeriodicalIF":9.0,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.20010","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142152728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diabetes risk reduction diet and risk of liver cancer and chronic liver disease mortality: A prospective cohort study","authors":"Yun Chen,&nbsp;Longgang Zhao,&nbsp;Su Yon Jung,&nbsp;Margaret S. Pichardo,&nbsp;Melissa Lopez-Pentecost,&nbsp;Thomas E. Rohan,&nbsp;Nazmus Saquib,&nbsp;Yangbo Sun,&nbsp;Fred K. Tabung,&nbsp;Tongzhang Zheng,&nbsp;Jean Wactawski-Wende,&nbsp;JoAnn E. Manson,&nbsp;Marian L Neuhouser,&nbsp;Xuehong Zhang","doi":"10.1111/joim.20007","DOIUrl":"10.1111/joim.20007","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>We aimed to prospectively evaluate the association between a diabetes risk reduction diet (DRRD) score and the risk of liver cancer development and chronic liver disease-specific mortality.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We included 98,786 postmenopausal women from the Women's Health Initiative-Observational Study and the usual diet arm of the Diet Modification trial. The DRRD score was derived from eight factors: high intakes of dietary fiber, coffee, nuts, polyunsaturated fatty acids, low intakes of red and processed meat, foods with high glycemic index, sugar-sweetened beverages (SSBs), and <i>trans</i> fat based on a validated Food-Frequency Questionnaire administered at baseline (1993–1998). Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) for liver cancer incidence and chronic liver disease mortality were estimated using Cox proportional hazards regression models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results and conclusion</h3>\u0000 \u0000 <p>After a median follow-up of 22.0 years, 216 incident liver cancer cases and 153 chronic liver disease deaths were confirmed. A higher DRRD score was significantly associated with a reduced risk of developing liver cancer (HR_{Tertile 3 vs. Tertile 1} = 0.69; 95% CI: 0.49–0.97; <i>P</i>_trend = 0.03) and chronic liver disease mortality (HR_{T3 vs. T1} = 0.54; 95% CI: 0.35–0.82; <i>P</i>_trend = 0.003). We further found inverse associations with dietary fiber and coffee, and positive associations with dietary glycemic index, SSBs, and <i>trans</i> fat. A higher DRRD score was associated with reduced risk of developing liver cancer and chronic liver disease mortality among postmenopausal women.</p>\u0000 </section>\u0000 </div>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"296 5","pages":"410-421"},"PeriodicalIF":9.0,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142138801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Apixaban, edoxaban and rivaroxaban but not dabigatran are associated with higher mortality compared to vitamin-K antagonists: A retrospective German claims data analysis","authors":"Christiane Engelbertz,&nbsp;Ursula Marschall,&nbsp;Jannik Feld,&nbsp;Lena Makowski,&nbsp;Stefan A. Lange,&nbsp;Eva Freisinger,&nbsp;Joachim Gerß,&nbsp;Günter Breithardt,&nbsp;Andreas Faldum,&nbsp;Holger Reinecke,&nbsp;Jeanette Köppe","doi":"10.1111/joim.20006","DOIUrl":"10.1111/joim.20006","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Vitamin-K antagonists (VKAs) have widely been replaced by non-VKA oral anticoagulants (NOACs). This includes Austria, Germany and Switzerland, where as VKA, instead of warfarin, the much longer-acting phenprocoumon is used, which was not compared to NOACs in clinical trials.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using administrative data from a large German health insurance, we included all anticoagulation-naïve patients with a first prescription of a NOAC or VKA between 2012 and 2020. We analysed overall survival, major adverse cardiac and cerebrovascular events, major thromboembolic events and major bleeding.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Overall, 570,137 patients were included (apixaban: 26.9%, dabigatran: 4.6%, edoxaban: 8.8%, rivaroxaban: 39.1% and VKA: 20.7% of these 99.4% phenprocoumon). In the primary analysis using a 1:1 propensity score matching-cohort (PSM-cohort), a significantly higher overall mortality was found for apixaban, edoxaban and rivaroxaban (all <i>p </i>&lt; 0.001) but not for dabigatran (<i>p</i> = 0.13) compared to VKA. In this PSM-cohort, 5-year mortality was 22.7% for apixaban versus 12.7% for VKA, 19.5% for edoxaban versus 11.4% for VKA, 16.0% for rivaroxaban versus 12.3% for VKA (all <i>p</i> &lt; 0.001) and 13.0% for dabigatran versus 12.8% for VKA (<i>p</i> = 0.06). The observed effect was confirmed in sensitivity analyses using un-weighted and three different weighted Fine–Gray regression models on the basis of the entire cohort.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In this large real-world analysis, apixaban, edoxaban and rivaroxaban, but not dabigatran, were associated with worse survival compared to VKA. These findings, consistent with a few other studies including phenprocoumon, cast profound doubts on the unreflected, general use of NOACs. Randomized trials should assess whether phenprocoumon might actually be superior to NOACs.</p>\u0000 </section>\u0000 </div>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"296 4","pages":"362-376"},"PeriodicalIF":9.0,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.20006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142102693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regarding: Adherence to guideline-recommended care of late-onset hypertension in females versus males: A population-based cohort study","authors":"Shanshan Huang,&nbsp;Yanli Chen,&nbsp;Dan Shan,&nbsp;Renquan Wang","doi":"10.1111/joim.20009","DOIUrl":"10.1111/joim.20009","url":null,"abstract":"&lt;p&gt;Dear Editor,&lt;/p&gt;&lt;p&gt;Bugeja et al. offered significant insights into the management of late-onset hypertension [&lt;span&gt;1&lt;/span&gt;]; however, several methodological and interpretive issues warrant further scrutiny.&lt;/p&gt;&lt;p&gt;The study's statistical analysis, while robust, may overlook subtle but clinically significant interactions between sex and other covariates. For instance, the adjusted hazard ratios (aHR) for the prescription of antihypertensive medications (aHR 0.98 for females vs. males) suggest a minor statistical difference that the authors deem non-clinically significant. However, given the large sample size, even small differences can translate into meaningful impacts at the population level. A more nuanced statistical approach, such as the use of interaction terms and stratified analyses, might uncover important sex-specific differences in treatment efficacy and adherence. Austin et al. emphasized the importance of understanding interactions in epidemiological research, which can provide a more detailed understanding of how sex may influence treatment outcomes [&lt;span&gt;2&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Furthermore, the study's reliance on retrospective data from administrative databases introduces potential biases. Although the authors adjusted for numerous covariates, the inherent limitations of such data sources, such as coding inaccuracies and unmeasured confounders, cannot be fully mitigated. The use of the ICD-10 coding system for hypertension diagnosis and subsequent treatment prescriptions may not accurately reflect the clinical nuances of patient management. Quan et al. noted that administrative data, while useful, often lack the granularity needed for precise clinical studies, potentially leading to misclassification biases that can skew results [&lt;span&gt;3&lt;/span&gt;]. Future research should consider these limitations and possibly integrate clinical data to enhance the accuracy of findings.&lt;/p&gt;&lt;p&gt;The interpretation of the results also warrants reconsideration. The authors conclude that there are no clinically meaningful sex-based differences in the initial management of late-onset hypertension. However, this interpretation might be premature. The study finds that females are less likely to be prescribed certain antihypertensive medications, such as Angiotensin-converting enzyme (ACE) inhibitors, compared to males (aHR 0.995). This subtle difference, while statistically modest, could reflect underlying disparities in clinical decision-making processes, possibly influenced by provider biases or patient preferences. Evidence has shown that such disparities can have long-term implications for health outcomes, suggesting the cumulative impact of small biases in clinical care over time [&lt;span&gt;4&lt;/span&gt;]. This highlights the need for a more detailed examination of prescribing practices and their long-term effects on patient outcomes.&lt;/p&gt;&lt;p&gt;Lastly, although the discussion section is comprehensive, it occasionally overgeneralizes findings. The assertion that “females","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"296 5","pages":"452-453"},"PeriodicalIF":9.0,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.20009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142118565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of NO pathway in the clinical picture of idiopathic systemic capillary leak syndrome","authors":"Maddalena Alessandra Wu,&nbsp;Chiara Cogliati,&nbsp;Emanuele Catena,&nbsp;Riccardo Colombo","doi":"10.1111/joim.20005","DOIUrl":"10.1111/joim.20005","url":null,"abstract":"&lt;p&gt;Dear Editor,&lt;/p&gt;&lt;p&gt;Clarkson's disease, also known as idiopathic systemic capillary leak syndrome (ISCLS), is a rare and potentially lethal paroxysmal permeability disorder characterized by unpredictable episodes of massive plasma leakage from the intravascular to the extravascular compartment, most often into muscular tissues, leading to shock and ultimately multiple organ failure.&lt;/p&gt;&lt;p&gt;The underlying pathophysiological mechanisms of ISCLS are not well understood. They are believed to involve hypersensitivity of the capillaries to inflammatory or immune system triggers, which result in the transitory derangement of inter-endothelial junctions, causing the abrupt loss of endothelial barrier function. Most ISCLS patients have a monoclonal gammopathy of undetermined significance, which is a characteristic trait in the adult form of ISCLS and has been hypothesized to play a role in the pathophysiology, although not yet characterized. Therefore, the term “monoclonal gammopathy of clinical significance” appears more appropriate with respect to Clarkson's disease. Patients’ sera, collected during the acute and intercritical phases, have been reported to significantly increase the permeability of human umbilical vein endothelial cells (ECs) compared to sera from healthy controls [&lt;span&gt;1&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Recently, it has been demonstrated experimentally that ECs derived from ISCLS patients were functionally hyperresponsive to the two permeabilizing factors vascular endothelial growth (VEGF) and histamine [&lt;span&gt;2&lt;/span&gt;]. There is evidence that the main alteration lies in the hyperactivation of the endothelial nitric oxide synthase (eNOS) in ISCLS-derived ECs. Furthermore, eNOS blockade by the administration of NG-nitro-&lt;span&gt;l&lt;/span&gt;-arginine methyl ester (NAME) improved vascular leakage in a mouse model of ISCLS after histamine or VEGF challenge [&lt;span&gt;2&lt;/span&gt;]. On the other hand, methylene blue, which blocks the nitric oxide (NO) pathway by inhibiting the guanylate cyclase [&lt;span&gt;3&lt;/span&gt;] and is generally used in conditions characterized by increased levels of NO, like septic shock [&lt;span&gt;4&lt;/span&gt;], did not show efficacy in ISCLS. There is only an anecdotal report of a patient who was successfully treated with methylene blue during an ISCLS crisis. Remarkably, this patient suffered from several attacks per year, and repeated administrations of methylene blue did not yield positive results [&lt;span&gt;5&lt;/span&gt;]. Furthermore, the measurement of circulating NO metabolites in both acute and intercritical sera revealed no significant difference in NO levels in samples from ISCLS patients compared to control [&lt;span&gt;1&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Given the suggested central role of the NO pathway in the pathogenesis of ISCLS flares and considering the intrinsic hyperresponsiveness of ISCLS ECs, we decided to assess the endothelial function of ISCLS patients in vivo using a NO-dependent noninvasive functional methodology. Specifically, we employed peripheral arterial tonome","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"296 5","pages":"449-451"},"PeriodicalIF":9.0,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.20005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142102694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hospitalization after hydroxychloroquine initiation in patients with heart failure with preserved ejection fraction and autoimmune disease","authors":"Munaza Riaz,&nbsp;Haesuk Park,&nbsp;Carl J. Pepine,&nbsp;Ashutosh M. Shukla","doi":"10.1111/joim.20004","DOIUrl":"10.1111/joim.20004","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Hydroxychloroquine (HCQ) reduces cardiovascular events among patients with autoimmune disorders and is being evaluated as a therapeutic option for populations with high-risk cardiovascular disease. However, recent studies have raised concerns about HCQ use and cardiovascular events.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To assess the association of HCQ initiation with heart failure–related and all-cause hospitalizations among patients with heart failure and preserved ejection fraction (HFpEF).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a cohort study of patients aged ≥18 years with diagnosed HFpEF and autoimmune disease using MarketScan Commercial and Medicare Supplemental databases (2007–2019). Patients were required to initiate HCQ after their first HFpEF diagnosis (HCQ users) or not (HCQ nonusers). For the patients in the HCQ users group, the first HCQ prescription date was assigned as the index date. Index date for the HCQ nonuser group was assigned by prescription-time distribution matching HCQ users, by utilizing the number of days from HFpEF diagnosis to the first HCQ prescription. After 1:≥3 propensity score (PS) matching, Cox proportional hazards regression models were used to compare HF-related and all-cause hospitalizations between users and nonusers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>After PS matching, 2229 patients (592 HCQ users and 1637 HCQ nonusers) were included. After controlling for covariates, patients who received HCQ had lower risks of HF-related hospitalization (adjusted hazard ratio, 0.44; 95% CI, 0.24–0.82) and all-cause hospitalization (adjusted hazard ratio, 0.69; 95% CI, 0.57–0.83) compared with patients not using HCQ.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Among patients with HFpEF and autoimmune disease, initiation of HCQ use was associated with a decreased risk of HF-related and all-cause hospitalizations.</p>\u0000 </section>\u0000 </div>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"296 5","pages":"399-409"},"PeriodicalIF":9.0,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142078657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of cancer on the mortality of patients with idiopathic inflammatory myopathies by flexible parametric multistate modelling","authors":"Weng Ian Che,&nbsp;Ralf Kuja-Halkola,&nbsp;Karin Hellgren,&nbsp;Ingrid E. Lundberg,&nbsp;Helga Westerlind,&nbsp;Fredrik Baecklund,&nbsp;Marie Holmqvist","doi":"10.1111/joim.20003","DOIUrl":"10.1111/joim.20003","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Patients with idiopathic inflammatory myopathies (IIM) have an increased risk of cancer, but their cancer-related disease burden remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>To explore how cancer might impact the mortality of patients with IIM and examine the associated prognostic factors for cancer and death.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We identified patients with IIM diagnosed between 1998 and 2020 and ascertained their cancer and death records via linkage to the Swedish healthcare and population registers. Transition hazards from IIM diagnosis to cancer and death were estimated in multistate models using flexible parametric methods. We then predicted the probability of having cancer or death, and the duration of staying alive at a given time from IIM and cancer diagnoses from a crude model. We also explored prognostic factors for progression to cancer and death in a multivariable model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of 1826 IIM patients, 310 (17%) were diagnosed with cancer before and 306 (17%) after IIM diagnosis. In patients diagnosed with <i>cancer after</i> IIM, the 5-year probability of death from cancer and from other causes was 31% and 18%, respectively, compared to 7% and 15% in patients without <i>cancer after</i> IIM. We reported several factors associated with risk of progression to cancer and death. Specifically, patients with <i>first cancer after</i> IIM who were older at IIM diagnosis, had cancer history, dermatomyositis and a cancer diagnosis within 1 year following IIM faced a greater cancer-specific mortality.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>We observed a substantial increase in mortality from cancer, compared to before, rather than other causes after a cancer diagnosis following IIM, suggesting an unmet medical need for effective cancer management in IIM patients. This finding, along with the identified prognostic factors, provides useful insight into future research directions for improving cancer management in IIM patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"296 4","pages":"336-349"},"PeriodicalIF":9.0,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.20003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141873693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clonal hematopoiesis of indeterminate potential and risk of neurodegenerative diseases","authors":"Xinyuan Liu,&nbsp;Huiwen Xue,&nbsp;Karin Wirdefeldt,&nbsp;Huan Song,&nbsp;Karin Smedby,&nbsp;Fang Fang,&nbsp;Qianwei Liu","doi":"10.1111/joim.20001","DOIUrl":"10.1111/joim.20001","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Little is known regarding the association between clonal hematopoiesis of indeterminate potential (CHIP) and risk of neurodegenerative diseases.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To estimate the risk of neurodegenerative diseases among individuals with CHIP.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a community-based cohort study based on UK Biobank and used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of any neurodegenerative disease, subtypes of neurodegenerative diseases (including primary neurodegenerative diseases, vascular neurodegenerative diseases, and other neurodegenerative diseases), and specific diagnoses of neurodegenerative diseases (i.e., amyotrophic lateral sclerosis [ALS], Alzheimer's disease [AD], and Parkinson's disease [PD]) associated with CHIP.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We identified 14,440 individuals with CHIP and 450,907 individuals without CHIP. Individuals with CHIP had an increased risk of any neurodegenerative disease (HR 1.10, 95% CI: 1.01–1.19). We also observed a statistically significantly increased risk for vascular neurodegenerative diseases (HR 1.31, 95% CI 1.05–1.63) and ALS (HR 1.50, 95% CI 1.05–2.15). An increased risk was also noted for other neurodegenerative diseases (HR 1.13, 95% CI 0.97–1.32), although not statistically significant. Null association was noted for primary neurodegenerative diseases (HR 1.06, 95% CI 0.96–1.17), AD (HR 1.04, 95% CI 0.88–1.23), and PD (HR 1.02, 95% CI 0.86–1.21). The risk increase in any neurodegenerative disease was mainly observed for <i>DNMT3A</i>-mutant CHIP, <i>ASXL1</i>-mutant CHIP, or <i>SRSF2</i>-mutant CHIP.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Individuals with CHIP were at an increased risk of neurodegenerative diseases, primarily vascular neurodegenerative diseases and ALS, but potentially also other neurodegenerative diseases. These findings suggest potential shared mechanisms between CHIP and neurodegenerative diseases.</p>\u0000 </section>\u0000 </div>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"296 4","pages":"327-335"},"PeriodicalIF":9.0,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141786657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SARS-CoV-2 spike protein acts as a β-adrenergic receptor agonist: A potential mechanism for cardiac sequelae of long COVID","authors":"Xiangning Deng,&nbsp;Hongtu Cui,&nbsp;Hao Liang,&nbsp;Xinyu Wang,&nbsp;Haiyi Yu,&nbsp;Jingjia Wang,&nbsp;Wenyao Wang,&nbsp;Dongyang Liu,&nbsp;Youyi Zhang,&nbsp;Erdan Dong,&nbsp;Yida Tang,&nbsp;Han Xiao","doi":"10.1111/joim.20000","DOIUrl":"10.1111/joim.20000","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Currently, pathophysiological mechanisms of post-acute sequelae of coronavirus disease-19-cardiovascular syndrome (PASC-CVS) remain unknown.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and results</h3>\u0000 \u0000 <p>Patients with PASC-CVS exhibited significantly higher circulating levels of severe acute respiratory syndrome-coronavirus-2 spike protein S1 than the non-PASC-CVS patients and healthy controls. Moreover, individuals with high plasma spike protein S1 concentrations exhibited elevated heart rates and normalized low frequency, suggesting cardiac β-adrenergic receptor (β-AR) hyperactivity. Microscale thermophoresis (MST) assay revealed that the spike protein bound to β₁- and β₂-AR, but not to D1-dopamine receptor. These interactions were blocked by β₁- and β₂-AR blockers. Molecular docking and MST assay of β-AR mutants revealed that the spike protein interacted with the extracellular loop 2 of both β-ARs. In cardiomyocytes, spike protein dose-dependently increased the cyclic adenosine monophosphate production with or without epinephrine, indicating its allosteric effects on β-ARs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Severe acute respiratory syndrome-coronavirus-2 spike proteins act as an allosteric β-AR agonist, leading to cardiac β-AR hyperactivity, thus contributing to PASC-CVS.</p>\u0000 </section>\u0000 </div>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"296 3","pages":"291-297"},"PeriodicalIF":9.0,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141786658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}