Journal of Internal Medicine最新文献

Dear Editor,

We read with enthusiasm the article [1] comparing standard and advanced (speckle-tracking) echocardiographic parameters measured in patients with Paget's disease of bone (PDB) and would like to bring the following comments.

First, Giaquinto et al. present a multicenter case–control study of patients with PDB and normal controls who underwent very detailed echocardiographic analyses. Although the analyses are detailed, these findings are mainly descriptive and do not necessarily guide practice. The authors may need to evaluate the predictive value of outcomes and prognosis independently among the standard and advanced echocardiographic parameters in the populations [2]. The optimal cut-off value for myocardial work and speckle-tracking parameters in receiver operating characteristic curve analysis should also be applied to help come up with predictive parameters [3].

Second, no significant difference was observed in global longitudinal strain, whereas the left ventricle ejection fraction (LVEF) was significantly lower between the groups in Table 3 (p < 0.05). However, left ventricle global longitudinal strain is a more sensitive method than LVEF for diagnosing mild systolic dysfunction, applying to patients suspected of having heart failure with normal LVEF [4], which is inconsistent with the results in the study.

In addition, global longitudinal strain and global work efficiency were significantly lower in patients with PDB than those in controls. In fact, left ventricle was divided into 18 segments for the exploration of the distribution of regional, however, segmental strain and myocardial work were not evaluated, which added value to explore the distribution of myocardial impairment [4, 5].

Huihui Wu and Dong Wang: Conception and design. Huihui Wu and Lihong Wang: Writing of the manuscript. All authors have reviewed and approved the final version of the manuscript.

The authors declare no conflicts of interest.

Yen FS, Hung YM, Huang JY, Hsu CC, Cheng WY, Hwu CM, et al. Effects of SGLT2 inhibitors on transplant survival and key clinical outcomes in heart transplant recipients with diabetes. J Intern Med. 2025;297(5):532-542. https://doi.org/10.1111/joim.20077

In the originally published article, the affiliation for Jing-Yang Huang was incorrectly listed.

The incorrect affiliation was:

“6 Institute of Medicine, Chung Shan Medical University, Taichung City, Taiwan”

The correct affiliations for Jing-Yang Huang are:

“6 Institute of Medicine, Chung Shan Medical University, Taichung, 402, Taiwan; Department of Medical Research, Chung Shan Medical University Hospital, Taichung, 402, Taiwan.”

We apologize for this error.

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 ex vivo 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.

Dear Editor,

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) [1]. 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 [2]. 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 [1]. 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 [1]. These findings lend support to the hypothesis that coexisting 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 [1]. 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 [3]. 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 [4]. 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.

The author declares no conflicts of interest.

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.

Dear Editor,

We thank Dr. Shamsulddin for his perspective [1] on our meta-analysis on intensive versus standard systolic blood pressure (SBP) control [2]. 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.

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.

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.

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.

The authors declare no conflicts of interest.

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.