Journal of Internal Medicine最新文献

{"title":"Precision oncology to overcome resistance in R/R AML in children and adults requires combinations of cytotoxic, targeted, and immunological treatments","authors":"Martin Jädersten,&nbsp;Ingrid Lilienthal,&nbsp;Christer Nilsson,&nbsp;Louisa Fredrikson,&nbsp;Cornelis Jan Pronk,&nbsp;Kristian Løvvik Juul-Dam,&nbsp;Mika Kontro,&nbsp;Nikolas Herold","doi":"10.1111/joim.70004","DOIUrl":"10.1111/joim.70004","url":null,"abstract":"<p>Although outcomes for newly diagnosed acute myeloid leukaemia (AML) have been incrementally improved over the last decades, management of relapsed and refractory (R/R) AML remains a medical challenge. A curative intent for R/R AML usually involves chemotherapy (with or without targeted therapy) with subsequent consolidation, including allogeneic haematopoietic stem cell transplantation. Despite this, long-term survival rates of R/R AML only reach approximately 10% in adults and 40% in children. Given this great unmet clinical need, this review outlines the current and emerging paradigms for preventing and treating R/R AML. Somatic mutations, gene expression, and functional drug testing are important for the selection of small molecule inhibitors of oncogenic signalling pathways (e.g., FLT3), menin inhibitors that disrupt leukemogenic programmes, inhibitors of isocitrate dehydrogenases to restore oncometabolic homoeostasis, and proapoptotic Bcl-2 homology 3 (BH3) mimetics, such as venetoclax. Targeting the recently identified resistance factor SAMHD1 promises to overcome resistance to cytarabine and fludarabine. Given the growing number of potential combinatorial drug regimens and the genetic heterogeneity of AML, real-time <i>ex vivo</i> drug response profiling to guide individualized treatment decisions will become an important complement. We argue that better outcomes for R/R AML critically depend on being guided by precision oncology to define the best combination of chemotherapy, targeted therapy, and immunological therapy informed by phenotypic and genotypic patient- and disease-specific parameters.</p>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"298 4","pages":"297-318"},"PeriodicalIF":9.2,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.70004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144797753","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: Standard and advanced echocardiographic study of patients with Paget's disease of bone: Evidence of a Pagetic heart disease?","authors":"Giuseppe Famularo","doi":"10.1111/joim.70011","DOIUrl":"10.1111/joim.70011","url":null,"abstract":"<p>Dear Editor,</p><p>I appreciate Giaquinto et al. sharing the findings of their case–control study on cardiac abnormalities in patients with Paget's disease of the bone (PDB) [<span>1</span>]. Even though patients and controls were matched for several cardiovascular risk factors such as age, sex, body mass index, and history of arterial hypertension, it remains unclear if the abnormal echocardiographic parameters the authors recognized in PDB patients resulted from either the disease itself or other unrelated conditions. The most specific cardiovascular manifestation of PDB is high-output heart failure due to the extensive arteriovenous shunting that leads to markedly increased blood flow through the Pagetic bone [<span>2</span>]. This is a rare complication that typically occurs in patients with advanced and metabolically active disease involving large portions of the skeleton. However, only 21 out of the 69 PDB patients they reported on had active disease according to elevated blood levels of total alkaline phosphatase, and 31 out of 69 had a limited involvement of the skeleton with a monostotic rather than polyostotic disease [<span>1</span>]. Furthermore, no significant differences in echocardiographic parameters were observed between patients with active and those with inactive disease and between patients with monostotic and those with polyostotic disease [<span>1</span>]. These findings lend support to the hypothesis that coexistin<i>g</i> conditions may be at play in damaging the myocardial function and structure, at least in a proportion of PDB patients. To rule out any interference, however, Giaquinto et al. excluded cases and controls with a spectrum of potential causes of cardiac impairment, but transthyretin cardiac amyloidosis (TTA) was not investigated [<span>1</span>]. The coexistence of TTA could have been suggested by some demographic, clinical, and echocardiographic characteristics that appear to be shared by both the PDB patients reported by Giaquinto et al. and the typical patients with TTA cardiomyopathy [<span>3</span>]. No study has so far ascertained the relative importance of TTA in PDB patients, and only one report has described a single patient with both PDB and TTA [<span>4</span>]. It is worth addressing the problem of unrevealed TTA as a source of bias when investigating the cardiovascular manifestations of PDB and the impact on the current analyses in the study by Giaquinto et al. It would be of interest if the authors could provide information on this issue.</p><p>The author declares no conflicts of interest.</p>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"298 5","pages":""},"PeriodicalIF":9.2,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.70011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144803026","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":"Hospital-treated infections and the risk and prognosis of amyotrophic lateral sclerosis: A population-based study","authors":"Yihan Hu,&nbsp;Charilaos Chourpiliadis,&nbsp;Caroline Ingre,&nbsp;Viktor H. Ahlqvist,&nbsp;Jiangwei Sun,&nbsp;Huan Song,&nbsp;Yudi Pawitan,&nbsp;Fredrik Piehl,&nbsp;Fang Fang","doi":"10.1111/joim.70008","DOIUrl":"10.1111/joim.70008","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Infection has been suspected as a risk factor for amyotrophic lateral sclerosis (ALS). However, previous research has focused on specific pathogens and rarely examined the influence of infection on disease progression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>To assess whether hospital-treated infections correlate with the risk and prognosis of ALS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using data from the Swedish Motor Neuron Disease Quality Registry, we conducted three nested case-control studies, including 1159 individuals diagnosed with ALS during 2015–2023 and 5795 age- and sex-matched population controls, 1558 full-sibling controls, and 680 spouse controls, respectively. We used conditional logistic regression to estimate the association of hospital-treated infections with subsequent risk of ALS and Cox model to assess the association of pre- or post-diagnostic infections with mortality after an ALS diagnosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Hospital-treated infections before diagnosis were associated with an increased risk of ALS in the population comparison (odds ratio [OR] 1.31; 95% confidence interval [CI] 1.15–1.49). A similar association was noted after excluding infections within 3-, 5-, or 10-years preceding ALS diagnosis and was confirmed in sibling and spouse comparisons, although results were not always statistically significant. Patients with a hospital-treated infection before diagnosis were more likely to present with bulbar symptoms, poorer functional status, and higher prevalence of anxiety and depressive symptoms at diagnosis than others. Pre-diagnostic infections were not associated with mortality, whereas post-diagnostic infections were associated with increased mortality (hazard ratio [HR] 1.89; 95%CI 1.59–2.24) among ALS patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Hospital-treated infections are associated with an increased risk of ALS and may modify its clinical presentation at diagnosis. Post-diagnostic infections are associated with poor survival in ALS.</p>\u0000 </section>\u0000 </div>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"298 4","pages":"349-360"},"PeriodicalIF":9.2,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.70008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144787921","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":"Choosing oral antihyperglycaemic drugs in people living with Type 2 diabetes and severe chronic kidney disease","authors":"Mikael Rydén","doi":"10.1111/joim.70002","DOIUrl":"10.1111/joim.70002","url":null,"abstract":"&lt;p&gt;Managing hyperglycaemia in individuals with Type 2 diabetes (T2D) and advanced chronic kidney disease (CKD) involves several important considerations [&lt;span&gt;1&lt;/span&gt;]. For instance, metformin is renally excreted, and a reduced estimated glomerular filtration rate (eGFR) increases the risk of drug accumulation, potentially leading to serious adverse events such as lactic acidosis. Although sulphonylureas and pioglitazone are primarily metabolized in the liver, their active metabolites are renally excreted, which—particularly in the context of impaired kidney function—may increase the risk of hypoglycaemia or fluid retention, respectively. SGLT2 inhibitors have limited glucose-lowering efficacy in patients with eGFR values below 20–25 mL/min/1.73 m&lt;sup&gt;2&lt;/sup&gt;. Additionally, GLP-1 receptor agonists promote weight loss, which may be undesirable in normal-weight patients, and insulin therapy, though often necessary, is associated with a heightened risk of hypoglycaemia and can be challenging to optimize in this vulnerable group. In contrast, the meglitinide repaglinide has been considered a particularly suitable oral agent under these circumstances. It undergoes hepatic metabolism, and only its inactive metabolites are excreted renally. Moreover, repaglinide's short duration of action and meal-time dosing provide safety and additional flexibility in glucose control.&lt;/p&gt;&lt;p&gt;Dipeptidyl peptidase-4 inhibitors (DPP-4i), such as sitagliptin and linagliptin, have been in clinical use for nearly two decades and are generally regarded as safe, with a favourable side-effect profile. Notably, their risk of inducing hypoglycaemia is significantly lower compared to sulphonylureas and meglitinides. This is attributed to their glucose-dependent mechanism of action, with insulinotropic effects markedly reduced at plasma glucose concentrations below approximately 4.5 mmol/L. Furthermore, DPP-4i are weight-neutral, which may be advantageous for patients with T2D and CKD in the normal or lower body mass index range. The pharmacokinetics of agents within this class vary. Thus, while sitagliptin is primarily excreted unchanged by the kidneys, linagliptin undergoes hepatic metabolism [&lt;span&gt;2&lt;/span&gt;]. Consequently, although sitagliptin requires dose adjustment in the context of reduced eGFR, linagliptin does not. Importantly, sitagliptin itself is not considered intrinsically nephrotoxic, even in the setting of advanced CKD. However, despite these favourable characteristics, clinical evidence on the safety and efficacy of DPP-4i in patients with T2D and Stage 5 CKD (eGFR &lt;15 mL/min/1.73 m&lt;sup&gt;2&lt;/sup&gt;) remains limited.&lt;/p&gt;&lt;p&gt;It is therefore timely to highlight the work by Hung et al., ‘Use of dipeptidyl peptidase-4 inhibitors is associated with lower risk of severe renal outcomes in pre-dialysis patients with Type 2 diabetes: A cohort study’ in the Journal of Internal Medicine [&lt;span&gt;3&lt;/span&gt;]. In this study, the authors investigated renal outcomes in adults with T2D","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"298 3","pages":"149-151"},"PeriodicalIF":9.2,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.70002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144783110","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":"Water scarcity and conservation and their role in obesity in nature and in humans","authors":"Richard J. Johnson,&nbsp;Johanna Painer-Gigler,&nbsp;Szilvia Kalgeropoulu,&nbsp;Sylvain Giroud,&nbsp;Paul G. Shiels,&nbsp;Mehmet Kanbay,&nbsp;Ana Andres-Hernando,&nbsp;Bernardo Rodriguez-Iturbe,&nbsp;Miguel A. Lanaspa,&nbsp;Peter Stenvinkel,&nbsp;Laura G. Sánchez-Lozada","doi":"10.1111/joim.70003","DOIUrl":"10.1111/joim.70003","url":null,"abstract":"<p>Increasing temperatures and water scarcity pose threats to animals living in the wild and humans. Here, we review biological mechanisms animals use to prevent dehydration. Fat and glycogen generate water during metabolism that can be used by many animals as a source of water. In hibernating animals, fat production is stimulated in the autumn by a vasopressin-dependent, carbohydrate-based metabolism that leads to thirst, increased water intake, and storage of glycogen and fat. As fall advances, the animals switch to fat-based metabolism with falling vasopressin levels, and actual entrance into torpor can be triggered when water becomes unavailable and/or unpredictable. Once in torpor, metabolic water is generated by fat metabolism along with a suppression of vasopressin and fall in serum osmolality that blocks thirst. We suggest that water production from fat does not keep up with demands, and that respiratory acidosis also develops as a consequence of hypoventilation, and this leads to the necessity of interbout arousals (IBA), in which the animal rewarms with a switch to carbohydrate metabolism that causes a rapid increase in water availability from the breakdown of glycogen that facilitates the ventilation needed to correct the acidemia. The animal then drops its metabolic rate again, allowing fat metabolism to continue. The observation that water deficit may be a stimulus for fat storage in hibernation carries significance for human obesity, especially in response to salt and sugar, as it suggests that hydration may be protective. These studies also provide an understanding of how glucagon-like peptide-1 agonists may cause weight loss.</p>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"298 6","pages":"562-577"},"PeriodicalIF":9.2,"publicationDate":"2025-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.70003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144774391","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: Systolic blood pressure targets below 120 mmHg are associated with reduced mortality: A meta-analysis","authors":"Felix Bergmann,&nbsp;Markus Zeitlinger,&nbsp;Anselm Jorda","doi":"10.1111/joim.70007","DOIUrl":"10.1111/joim.70007","url":null,"abstract":"<p>Dear Editor,</p><p>We thank Dr. Shamsulddin for his perspective [<span>1</span>] on our meta-analysis on intensive versus standard systolic blood pressure (SBP) control [<span>2</span>]. Although our findings show consistent benefits of intensive SBP control, we agree that identifying individuals who are most likely to benefit or experience harm remains a significant challenge.</p><p>Generalizability is a common limitation of trial-level meta-analyses, particularly when the included studies are geographically concentrated. In our analysis, most participants were enrolled in studies conducted in North America and East Asia. Although heterogeneity across study populations may compromise the precision and interpretability of pooled effect estimates, a certain degree of clinical and methodological variation is essential to support the external validity and applicability of meta-analytic findings. Besides geographical diversity, the included studies enrolled patients with different risk profiles, including diabetes, history of stroke, and cardiovascular disease of varying severity. Nonetheless, our subgroup analyses did not show significant heterogeneity of treatment effect across these clinical strata, suggesting a consistency that could be interpreted as a pragmatic proxy for real-world variability. However, this does not serve as a substitute for specifically designed regional studies, which would be required to confirm the benefits of intensive SBP control in genetically diverse populations and within different healthcare systems.</p><p>Finally, the risk of adverse events, such as the incidence of syncope, acute kidney injury and electrolyte disturbances, may also differ between geographical and clinical subgroups. These aspects of heterogeneity are rarely addressed in clinical trials and meta-analyses, which are often limited to subgroup analyses for efficacy outcomes.</p><p>Although we welcome the call for global validation, we believe our findings provide robust evidence supporting the benefits of intensive blood pressure lowering across diverse populations. Clinicians should use this evidence to guide personalized treatment decisions.</p><p>The authors declare no conflicts of interest.</p>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"298 4","pages":""},"PeriodicalIF":9.2,"publicationDate":"2025-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.70007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144774388","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: Systolic blood pressure targets below 120 mm Hg are associated with reduced mortality: A meta-analysis","authors":"Ahmed B. Shamsulddin","doi":"10.1111/joim.70006","DOIUrl":"10.1111/joim.70006","url":null,"abstract":"&lt;p&gt;Dear Editor,&lt;/p&gt;&lt;p&gt;The meta-analysis by Bergmann et al. [&lt;span&gt;1&lt;/span&gt;] published in &lt;i&gt;Journal of Internal Medicine&lt;/i&gt; provides a significant synthesis, concluding that intensive systolic blood pressure (SBP) control (&lt;120 mm Hg) reduces mortality and MACE in high-risk individuals. This finding could reinforce a dominant narrative that “lower is always better” for SBP, universally applicable. However, the “insight” arises when considering the study's own highlighted limitations and the geographical concentration of the included RCTs (primarily North America and East Asia). This prompts a reconsideration of how these important findings are translated into global clinical practice.&lt;/p&gt;&lt;p&gt;Why is this reconsideration needed now? The increasing recognition of global health disparities and the influence of diverse socio-environmental and genetic factors on disease presentation and treatment response means that a one-size-fits-all approach, even for well-established interventions, may fall short. Extant therapeutic guidelines often strive for universality, but the gap in current understanding is how to effectively adapt evidence from specific trial populations to the vast heterogeneity of real-world patients globally. Simply stating a pooled benefit without robustly addressing generalizability overlooks this critical translational step.&lt;/p&gt;&lt;p&gt;This analysis by Bergmann et al., therefore, offers a new framing for future research: Instead of solely focusing on whether intensive SBP control works, the emphasis should shift to for whom, under what conditions, and with what regional adaptations. The generalizability point is not just a caveat; it is a call to extend the literature through trials specifically designed to assess intensive SBP strategies in underrepresented regions (e.g., Middle East, Africa, and South America), potentially incorporating cross-disciplinary thinking from public health and implementation science to understand contextual barriers and facilitators.&lt;/p&gt;&lt;p&gt;Furthermore, the consistent signal of increased adverse events (hypotension, syncope, AKI) [1] is not merely a secondary concern but a primary driver for the practical implication of individualized therapy. The challenge now is to move beyond simply acknowledging this trade-off. Indeed, if the profound cardiovascular benefits demonstrated by Bergmann et al. could be consistently replicated across all global regions and achieved without the burden of these significant adverse effects, it would undoubtedly represent a paradigm shift in cardiovascular prevention. Therefore, the future direction must be proactive: To discover and validate targeted strategies—perhaps guided by pharmacogenomics, precision risk stratification for adverse events, or novel co-therapies—that can uncouple the desired cardiovascular benefits from the concerning harms.&lt;/p&gt;&lt;p&gt;To convince a potentially skeptical audience that this nuance is paramount, I argue that the true advancement lies not just in dem","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"298 4","pages":"363-364"},"PeriodicalIF":9.2,"publicationDate":"2025-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.70006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144774389","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":"The pharmacotherapeutic potential of neuropeptide Y for chronic pain","authors":"Al A. Nie,&nbsp;Bradley K. Taylor","doi":"10.1111/joim.20118","DOIUrl":"10.1111/joim.20118","url":null,"abstract":"<p>Chronic pain is a major medical problem that requires new therapeutic options. Discovered by Victor Mutt in 1982, neuropeptide Y (NPY) is rapidly emerging as a master regulator of pain relief. Genetic knockdown of NPY or pharmacological inhibition of its receptors demonstrates that NPY signaling tonically inhibits indices of chronic inflammatory and neuropathic pain. Primary targets of NPY analgesia include neurons in the dorsal horn of the spinal cord and the parabrachial nucleus of the brain that express the Npy1r (Y1) receptor. NPY signaling is enhanced following injury, and endogenous analgesic synergy between Y1 receptors and mu opioid receptors maintain chronic pain sensitization in a latent state of remission. We propose that disruptions to endogenous NPY analgesia may mediate pathological transitions from acute to chronic pain, which could be treated by CNS administration of Y1 agonists or Npy2r (Y2) agonists or antagonists, depending on the pain state. Chemogenetic manipulations or targeted ablations in rodent models of chronic inflammation or peripheral nerve injury establish that spinal Y1-interneurons are necessary and sufficient to elicit behavioral signs of both the sensory and affective dimensions of pain. Transcriptomic and in situ hybridization studies revealed three primary subpopulations of spinal Y1-interneurons that are conserved in higher order mammals, including non-human primates and humans. Spinally directed (intrathecal) administration of Y1-selective pharmacological agonists inhibit pronociceptive neurons that co-express Y1 and gastrin-releasing peptide to inhibit neuropathic pain. To circumvent highly invasive administration routes, ongoing studies are leveraging the intranasal route for delivery of NPY into the brain.</p>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"298 4","pages":"280-296"},"PeriodicalIF":9.2,"publicationDate":"2025-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.20118","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144774390","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":"Low-protein diet for chronic kidney disease: Evidence, controversies, and practical guidelines","authors":"Denise Mafra,&nbsp;Isabela Brum,&nbsp;Natália A. Borges,&nbsp;Viviane O. Leal,&nbsp;Denis Fouque","doi":"10.1111/joim.20117","DOIUrl":"10.1111/joim.20117","url":null,"abstract":"<p>The benefits of a low-protein diet (LPD) in patients with altered kidney function remain controversial. Dietary intake studies are inherently complex and may present numerous biases that must be understood and controlled. Due to these challenges, the scientific evidence in this area remains limited and is subject to dispute. However, there is abundant literature showing that excessive protein intake in these patients is linked to cardiovascular issues, oxidative stress, hyperphosphatemia, bone mineral disease, metabolic acidosis, inflammation, and gut dysbiosis, contributing to kidney damage and other concurrent systemic disorders. An LPD remains a valuable recommendation for non-dialysis chronic kidney disease (CKD) patients if age, nutritional status, and disease complications are carefully considered to ensure optimal outcomes. On the one hand, excessive protein intake may lead to the accumulation of nitrogenous waste products, thereby burdening renal function. On the other hand, overly restrictive protein consumption can lead to muscle mass loss, potentially worsening clinical outcomes and patient prognosis. This narrative review highlights the harmful impact of a high-protein diet on kidney function, particularly for those with preexisting kidney impairment or a predisposition to CKD. It also discusses the importance of an individualized and well-monitored protein intake strategy to balance the benefits of protein restriction with the risks of malnutrition.</p>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"298 4","pages":"319-335"},"PeriodicalIF":9.2,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.20117","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144751948","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":"Remnant cholesterol as a driver for atherosclerosis in patients with type 2 diabetes: Insights from a long-term prospective cohort study","authors":"Heinz Drexel,&nbsp;Laura Schnetzer,&nbsp;Andreas Leiherer,&nbsp;Peter Fraunberger,&nbsp;Arthur Mader,&nbsp;Christoph H. Saely,&nbsp;Andreas Festa","doi":"10.1111/joim.70001","DOIUrl":"https://doi.org/10.1111/joim.70001","url":null,"abstract":"","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"298 3","pages":"268-272"},"PeriodicalIF":9.2,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144892506","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}