Journal of Personalized Medicine最新文献

{"title":"Laparoscopic Lymph Node Assessment Prior to Open Radical Hysterectomy-A Two-Center Retrospective Study on Individualized Surgical Management of Early-Stage Cervical Cancer.","authors":"Magdalena Postl, Christoph Grimm, Melina Danisch, Patrik Petrov, Mara Mantovan, Alexander Reinthaller, Eva Langthaler, Stephan Polterauer, Christian Marth, Nicole Concin, Alain Gustave Zeimet","doi":"10.3390/jpm16090475","DOIUrl":"10.3390/jpm16090475","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Recent evidence suggests open radical hysterectomy is safer than radical hysterectomy by minimally invasive surgery (MIS) in early-stage cervical cancer. This study evaluated the oncological safety of laparoscopic lymph node assessment followed by open radical hysterectomy and the rate of unnecessary laparotomies avoided compared with a completely open approach. <b>Methods</b>: This two-center retrospective study included patients with cervical cancer FIGO stage ≤ Ib3 treated at two Austrian centers between 2015 and 2023. Patients undergoing laparoscopic lymph node assessment followed by open radical hysterectomy were compared with a matched historical cohort treated with primary open surgery between 2012 and 2017. Recurrence rates and progression-free survival (PFS) were compared using univariate and multivariate analyses. <b>Results</b>: In total, 130 patients were included: 79 (60.8%) underwent the combined approach and 51 (39.2%) the completely open approach. Recurrence rates (10.1% vs. 5.9%, <i>p</i> = 0.53) and median PFS (<i>p</i> = 0.36; median 26.0 vs. 71.3 months) did not differ between the two approaches. All patients underwent thorough preoperative radiologic and clinical assessment without suspected nodal metastases and were scheduled for radical hysterectomy with prior nodal assessment by MIS or open surgery. Intraoperative lymph node metastases were incidentally detected in 21/130 (16.2%) patients (combined approach <i>n</i> = 12 [15.2%] vs. open approach <i>n</i> = 9 [17.6%]). In cases of positive lymph nodes, surgery was abandoned without performing open radical hysterectomy and patients were referred to chemoradiotherapy. The needed to treat number to prevent one unnecessary open surgery was 6.25. <b>Conclusions</b>: Laparoscopic lymph node assessment before open radical hysterectomy appears oncologically safe, with comparable recurrence rates and PFS, and could spare one unnecessary laparotomy in every 7th patient with early-stage cervical cancer undergoing the combined approach.</p>","PeriodicalId":16722,"journal":{"name":"Journal of Personalized Medicine","volume":"16 9","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13608262/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149039365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ramadan Fasting in Metabolic Dysfunction-Associated Steatotic Liver Disease: Linking the Gut-Mitophagy-Circadian Axis to Endothelial Dysfunction and Hepatic Outcomes.","authors":"Musaab Ahmed, Nisha Shantakumari, Safaa Badi, Mohamed H Ahmed","doi":"10.3390/jpm16090474","DOIUrl":"10.3390/jpm16090474","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatotic liver disease (MASLD) is the predominant etiology of chronic liver disease and the leading factor to liver-related mortality. The endothelial dysfunction is a significant contributor to the onset of cardiovascular disease and is closely linked to MASLD. Previous studies have shown that changes in diet influence both MASLD and endothelial function and modify their risk factors. A small number of studies have evaluated the possible effects of Ramadan fasting on MASLD, related endothelial dysfunction and the gut-mitophagy-circadian axis. The aim of this narrative review is to evaluate the impacts of Ramadan fasting on MASLD, hepatic complications, related endothelial dysfunction and the gut-mitophagy-circadian axis. This review integrates endothelial dysfunction, gut microbiota, mitophagy, and circadian rhythm into a single mechanistic framework. We performed searches of SCOPUS and the PubMed databases using diverse search keywords. The review targeted scholarly English articles from the year 2000 to 2026. The review included seventy-three studies. Ramadan fasting might enhance MASLD, hepatic complications, and associated endothelium dysfunction and alter risk factors by facilitating weight loss, ameliorating insulin resistance, enhancing mitophagy, and inducing alterations in gut microbiota and circadian gene expression. Further studies are necessary to assess safety and efficacy of Ramadan fasting on MASLD, hepatic complications and related endothelial function. Circadian control offers a significant molecular foundation connecting Ramadan fasting to metabolic health.</p>","PeriodicalId":16722,"journal":{"name":"Journal of Personalized Medicine","volume":"16 9","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13608236/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149039395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Tumor-Bed Boost Irradiation in Early-Stage Breast Cancer 30 Years After the Landmark Trials: What Is New?","authors":"Ilaria Benevento, Angela Solazzo, Francesca Tortoreto, Genoveva Ionela Boboc, Barnaba Floreno, Luciana Rago, Barbara D'Andrea, Antonietta Montagna, Antonella Bianculli, Aldo Piscitelli, Fabrizio Sanna, Salvatrice Campoccia, Antonella Ciabattoni, Grazia Lazzari","doi":"10.3390/jpm16090473","DOIUrl":"10.3390/jpm16090473","url":null,"abstract":"<p><p>Breast-conserving surgery followed by adjuvant whole-breast irradiation (WBI) remains the standard of care for patients with early-stage breast cancer. In this setting, irradiation of the tumor bed with an additional boost dose has historically been used to reduce the risk of ipsilateral breast tumor recurrence (IBTR). Major randomized trials established that boost irradiation improved local control, particularly in younger patients, but did not confer a consistent overall survival (OS) benefit and was associated with increased late toxicity, like fibrosis, and poorer cosmetic outcomes as well. More recent evidence, including systematic reviews and contemporary consensus recommendations, suggests that boost irradiation may be safely omitted in selected low-risk patients, especially when the estimated absolute reduction in 10-year local recurrence is less than 3%. At the same time, the routine use of boost irradiation has been challenged by modern systemic therapy treatments questioning if boost could be really omitted in this set. Further advances in radiation techniques are redefining the scheduling and timing of boost administration, shifting from a conventional fractionation to hypofractionation and from the sequential (SEB) to simultaneous delivery with simultaneous integrated boost (SIB). In light of increasingly minimally invasive surgery and a de-escalation RT policy, unresolved clinical issues still remain about the management of positive or close margins and the role of boost irradiation in ductal carcinoma in situ. This narrative review summarizes the biological rationale, historical trial evidence, and recent literature addressing these evolving scenarios. Current evidence supports a more individualized approach to boost prescription based on recurrence risk, patient age, tumor biology, margin status, treatment techniques (surgery and radiotherapy), and patient preference.</p>","PeriodicalId":16722,"journal":{"name":"Journal of Personalized Medicine","volume":"16 9","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13608340/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149039356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Factors Associated with Anxiety Disorders in Adults with Childhood Hypospadias Repair: Results from the F.R.E.S.H. Study.","authors":"Michele Gnech, Massimiliano Buoli, Federica Fanti, Giulia Rotondi, Federica Marceca, Francesca Mitzman, Fabio Ciamarra, Giulia Garelli, Dario Guido Minoli, Erika Adalgisa De Marco, Daniele Stroppa, Massimo Di Grazia, Camilla Taverna, Eduje Thomas, Marco Castagnetti, Gianantonio Manzoni, Alfredo Berrettini","doi":"10.3390/jpm16090472","DOIUrl":"10.3390/jpm16090472","url":null,"abstract":"<p><p><b>Objectives:</b> This study aimed to evaluate the prevalence of pathological anxiety and to identify clinical, functional, and surgical factors associated with anxiety disorders in adults who underwent hypospadias repair during childhood. <b>Patients and Methods:</b> This cross-sectional analysis included adult males (≥18 years) previously treated surgically for hypospadias in childhood who underwent clinical evaluation and completed validated questionnaires assessing anxiety (State-Trait Anxiety Inventory, STAI-Y1/Y2), depression (Beck Depression Inventory-II), urological function (uroflowmetry and International Prostate Symptom Score), sexual function, and genital perception. Pathological anxiety was defined as STAI-Y1 ≥ 40. Patients with and without anxiety were compared using univariate analyses, and variables reaching statistical significance were entered into a binary logistic regression model to identify clinical variables independently associated with anxiety. <b>Results:</b> A total of 302 patients who underwent hypospadias surgery between 1975 and 2005 were included in this study. Of the 302 traced patients, 113 (37.4%) were contacted successfully, and a total of 36 adult male patients met the inclusion criteria for this study (mean age at assessment 23.6 years). Pathological anxiety was present in 14 patients (38.9%). Compared with non-anxious individuals, anxious patients were younger at assessment (<i>p</i> = 0.012), showed more impaired voiding dynamics, with lower flow index values (<i>p</i> = 0.060), and reported more severe urinary symptoms (<i>p</i> = 0.050). Depressive symptoms were significantly higher in the anxiety group (BDI-II: 9.5 vs. 3.1; <i>p</i> < 0.001) and were independently associated with pathological anxiety on multivariable analysis (OR 1.84, 95% CI 1.16-2.92; <i>p</i> = 0.01). Postoperative complications were more frequent and more severe among anxious patients, although this did not reach statistical significance. Subjective and objective aesthetic outcomes did not differ between groups. <b>Conclusions:</b> This study demonstrates that anxiety in adults treated for hypospadias during childhood is more closely related to functional urinary impairment, surgical complications, and depressive symptoms than to aesthetic outcomes. These findings emphasise the need for long-term, multidisciplinary follow-up incorporating routine mental health assessment. Early psychological screening and targeted supportive interventions may be associated with better functional and psychosocial outcomes, supporting a holistic, integrated model of care for hypospadias patients.</p>","PeriodicalId":16722,"journal":{"name":"Journal of Personalized Medicine","volume":"16 9","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13608580/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149039451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A New Gain-of-Function NLRP1 Variant Is Associated with Inflammasome Activation and Disease Severity in SLC25A38 Congenital Sideroblastic Anemia Case Report.","authors":"María Sánchez-Villalobos, Eulalia Campos Baños, Elena Martínez-Balsalobre, Miriam Pinilla-Marquínez, Verónica Navarro-Ramírez, Thomas Macartney, Laura Hurtado-Navarro, David Hernández-García, Miguel Blanquer, Pablo Pelegrín, Eduardo Salido-Fierrez, Ana Belén Pérez-Oliva","doi":"10.3390/jpm16090471","DOIUrl":"10.3390/jpm16090471","url":null,"abstract":"<p><p>Inflammasomes play a pivotal role in inflammation and infection, but the clinical relevance of inflammasomes goes beyond infectious disease. Here, we report a novel variant in the NLRP1 gene (p.V939M) identified in a patient with congenital sideroblastic anemia due to a homozygous SLC25A38 mutation. This patient exhibits severe anemia, iron overload, and dependence on frequent transfusions. Functional characterization of peripheral blood mononuclear cells from the patient revealed constitutive activation of the NLRP1 inflammasome in primary cells, evidenced by increased processing of NLRP1, cleavage of CASP1, and ASC oligomerization. Moreover, in a speck in vitro assay, the newly identified genetic variant increases ASC oligomerization, and using ex vivo erythroid differentiation assays with patient-derived cells, we demonstrated that pharmacological inhibition of CASP1 enhances erythrocyte formation. This patient-derived NLRP1 variant was evaluated in a newly generated human NLRP1 knockdown system using CRISPR-Cas9 in K562 cells, in combination with ferroptotic/oxidative stress induction to mimic patient clinical features, and our results indicate that the presence of NLRP1 p.V939M, together with enhanced ferroptosis, may contribute to the patient's phenotype. Furthermore, both CASP1 inhibition and ferroptosis inhibition further enhance the restoration of erythroid colony formation from primary progenitor cells derived from the patient. Therefore, our study identifies a novel NLRP1 inflammasome variant involved in human erythropoiesis and highlights its possible contribution to the pathogenesis of congenital sideroblastic anemia, providing a basis for the development of new potential therapeutic strategies.</p>","PeriodicalId":16722,"journal":{"name":"Journal of Personalized Medicine","volume":"16 9","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13608223/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149039423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Cytochrome P450 and P-glycoprotein Gene Polymorphisms on the Risk of Hemorrhagic Complications in Older Patients with Non-Valvular Atrial Fibrillation Treated with Rivaroxaban.","authors":"Ivan V Sychev, Andrey P Kondrakhin, Sherzod P Abdullaev, Pavel O Bochkov, Svetlana N Tuchkova, Lyubov V Selivanova, Denis S Fedorinov, Olga A Milovanova, Karin B Mirzaev, Dmitry A Sychev","doi":"10.3390/jpm16090470","DOIUrl":"10.3390/jpm16090470","url":null,"abstract":"<p><p><b>Background:</b> The administration of direct oral anticoagulants to older adults requires careful risk stratification against a backdrop of polypharmacy and age-related renal function decline. The role of single nucleotide polymorphisms in cytochrome P450 genes and efflux transporters in this context remains a clinically understudied issue. This study aimed to investigate the association of <i>ABCB1</i>, <i>CYP3A4</i>, and <i>CYP3A5</i> allelic variants with the safety of rivaroxaban therapy in geriatric patients with non-valvular atrial fibrillation (AF). <b>Materials and Methods:</b> This prospective cohort study consecutively enrolled 94 patients (mean age 83.2 ± 9.2 years). Rivaroxaban trough plasma concentrations (Cmin,ss ) were quantified using a validated high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) assay. Real-time polymerase chain reaction was utilized for the molecular genetic profiling of the <i>ABCB1</i> (rs1045642, rs2032582), <i>CYP3A4*22</i> (rs35599367), and <i>CYP3A5*3</i> (rs776746) loci. Comorbidity severity and the spectrum of drug-drug interactions were evaluated as additional predictors. <b>Results:</b> Clinically relevant hemorrhagic complications were documented in 36.2% (<i>n</i> = 34) of the monitored patients. A significant association was established between the homozygous CC genotype at the <i>ABCB1</i> rs1045642 locus and increased bleeding propensity (odds ratio [OR] 2.42; 95% CI: 1.02-5.74; <i>p</i> = 0.042), whereas the alternative TT variant was associated with a pronounced protective effect. No statistically significant correlations were identified for biotransformation isoenzyme markers (<i>CYP3A4*22</i>, <i>CYP3A5*3</i>). Anticoagulant metrics were comparably distributed across groups and showed no dependence on genetic status. The leading non-genetic factors associated with hemorrhage were advanced age (<i>p</i> < 0.0001), progressive glomerular filtration rate decline (CKD stages 3b-4; <i>p</i> = 0.0009), and pharmacokinetic/pharmacodynamic interference from the co-administration of amiodarone (OR 3.61), non-steroidal anti-inflammatory drugs, and antiplatelet agents. The validated HAS-BLED score demonstrated no predictive power within the comorbid conditions of this cohort (<i>p</i> = 0.052). <b>Conclusions:</b> The <i>ABCB1</i> rs1045642 (C3435T) polymorphism is associated with the occurrence of hemorrhagic events. Implementing pharmacogenetic testing of the P-glycoprotein transporter combined with a rigorous audit of renal excretory function and concomitant therapy management may optimize the safety profile of rivaroxaban in geriatric practice. These findings warrant confirmation in a larger cohort.</p>","PeriodicalId":16722,"journal":{"name":"Journal of Personalized Medicine","volume":"16 9","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13608412/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149039355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment-Resistant Depression as a Heterogeneous Clinical Syndrome: A Personalized Medicine Framework for Diagnostic Reassessment, Suicide Risk, and Mechanism-Based Treatment.","authors":"Davoud Amiri, Swetang J Shah, Lamberto Briziarelli, Sara Amiri, Barry Karlsson","doi":"10.3390/jpm16090468","DOIUrl":"10.3390/jpm16090468","url":null,"abstract":"<p><p><b>Background:</b> Treatment-resistant depression (TRD) is an operational category based on inadequate outcome after adequate antidepressant treatment. The same label may encompass insufficient treatment exposure, an incorrect primary diagnosis, clinically important comorbidity, or depressive illnesses with different maintaining mechanisms. This heterogeneity limits the clinical meaning of treatment history alone and complicates individualized care. <b>Objective:</b> To integrate evidence on diagnostic reassessment, suicide risk, neurobiology, psychological and functional factors, and treatment, and to define a clinically testable personalized medicine framework for TRD. Methods: Targeted PubMed/MEDLINE searches were conducted from database inception through 31 July 2026 and supplemented by reference-list searching. Two authors independently assessed publications for relevance, and disagreements were resolved by discussion and consensus. Ninety-six sources were included and synthesized narratively. <b>Results:</b> Inadequate exposure or adherence can produce pseudo-resistance, whereas bipolar spectrum illness, neurodevelopmental or trauma-related conditions, personality pathology, sleep or substance-related disorders, and medical disease may represent alternative diagnoses, comorbidities, or modifiers of treatment course. Glutamatergic signaling, impaired plasticity, stress-system dysregulation, inflammation, circadian disturbance, metabolism, and neural circuitry contribute to heterogeneity at the group level but do not define validated individual subtypes. Established pharmacological, psychological, and neuromodulatory interventions should be selected according to diagnosis, severity, urgency, previous response, comorbidity, functional impairment, safety, feasibility, and patient preference. <b>Conclusions:</b> TRD is an operational treatment-history category, not a unitary disease. A personalized medicine approach begins with confirmation of major depressive disorder, adequate treatment exposure and adherence, followed by parallel treatment of depression and clinically relevant comorbidity. Biomarkers should guide allocation only when they provide prospectively validated predictive value beyond high-quality clinical and functional assessment.</p>","PeriodicalId":16722,"journal":{"name":"Journal of Personalized Medicine","volume":"16 9","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13608669/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149039435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cell-Based Therapies for Periodontal Regeneration: A Systematic Review and Meta-Analysis with Future Implications for Personalized Medicine.","authors":"Rafael X Erazo Vaca, Gabriela G Zambrano Manzaba, Luis-Chauca Bajaña, Andrea-Ordoñez Balladares, Andres-Villao Leon, Nayely J Teran Sanchez, Gema N Mendoza Manzaba, Rito A Salazar Román, Jorge L Teran Sanchez, David A Flor Ronquillo, Byron-Velasquez Ron","doi":"10.3390/jpm16090469","DOIUrl":"10.3390/jpm16090469","url":null,"abstract":"&lt;p&gt;&lt;p&gt;&lt;b&gt;Background/Objectives&lt;/b&gt;: Periodontitis is a chronic inflammatory disease characterized by progressive destruction of the periodontal supporting tissues. Regenerative responses may vary according to patient-related biological characteristics, periodontal defect morphology, the local inflammatory microenvironment, cellular source, biomaterial selection, and delivery strategy. Cell-based regenerative therapies may therefore provide a biological foundation for the future development of personalized periodontal regenerative approaches. This systematic review and meta-analysis evaluated the effectiveness of cell-based therapies for periodontal regeneration and considered how the current evidence may inform future personalized regenerative strategies. &lt;b&gt;Methods&lt;/b&gt;: A comprehensive electronic search was conducted in MEDLINE via PubMed, Web of Science, Embase, and the Cochrane Library, with additional searches performed in SciELO and Latindex, in accordance with PRISMA guidelines. Randomized and quasi-randomized controlled clinical trials evaluating cell-based regenerative therapies for periodontal defects were included. The primary outcomes were clinical attachment level (CAL) gain and probing depth (PD) reduction, while radiographic bone regeneration was considered a secondary outcome. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated using random-effects models. Leave-one-out sensitivity analyses were performed to assess the stability of the pooled estimates. &lt;b&gt;Results&lt;/b&gt;: Six clinical trials were included in the qualitative synthesis, and five contributed to the quantitative analysis. Cell-based regenerative therapies showed a small, non-significant effect for CAL gain (SMD = 0.17; 95% CI: -0.12 to 0.45; I&lt;sup&gt;2&lt;/sup&gt; = 0%) and PD reduction (SMD = 0.13; 95% CI: -0.22 to 0.48; I&lt;sup&gt;2&lt;/sup&gt; = 33.0%). Radiographic bone regeneration showed a larger favorable effect, although statistical significance was not reached and substantial heterogeneity was present (SMD = 1.25; 95% CI: -0.08 to 2.58; I&lt;sup&gt;2&lt;/sup&gt; = 88.2%). Leave-one-out analyses did not materially alter the non-significant interpretation for CAL or PD, although some variation in effect magnitude and direction was observed. Radiographic bone regeneration was more sensitive to the exclusion of individual studies. Overall, superiority of cell-based regenerative therapies over control interventions was not demonstrated. Risk-of-bias assessment indicated a low overall risk for most randomized trials, with some concerns in one trial and moderate risk in the quasi-randomized study. &lt;b&gt;Conclusions&lt;/b&gt;: Cell-based regenerative therapies showed preliminary but inconclusive signals of benefit for periodontal regeneration. However, no statistically significant superiority over control interventions was demonstrated for CAL gain, PD reduction, or radiographic bone regeneration. Further well-designed clinical trials are required before these approaches can","PeriodicalId":16722,"journal":{"name":"Journal of Personalized Medicine","volume":"16 9","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13608774/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149039474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Complex Screening for Congenital Cardiovascular Malformations.","authors":"Eszter Hódi, Éva Horváth-Varga, Márta Katona, Hajnalka Orvos, Áron Lajkó, Zsófia Fritsch, Szabolcs Várbíró, Zita Gyurkovits","doi":"10.3390/jpm16090467","DOIUrl":"10.3390/jpm16090467","url":null,"abstract":"&lt;p&gt;&lt;p&gt;&lt;b&gt;Importance:&lt;/b&gt; Congenital heart defects constitute the most prevalent developmental abnormality. Among these, critical congenital heart defects are associated with substantial morbidity and mortality if not promptly identified. &lt;b&gt;Objective:&lt;/b&gt; To evaluate the screening performance of a newborn protocol combining prenatal ultrasonography, postnatal physical examination, and pulse oximetry screening, with particular attention being paid to the timing of the postnatal examination. This is an evaluation of screening performance in a single centre and not a study of birth prevalence. &lt;b&gt;Methods:&lt;/b&gt; We performed a retrospective cohort study of all live-born infants delivered at University of Szeged, Hungary, between 2019 and 2024. Screening comprised prenatal ultrasonography, postnatal physical examination within 24 h and at a 48-72 h range, and pulse oximetry screening at 24 ± 6 h. The primary outcome was an echocardiographically confirmed congenital heart defect, classified as critical, severe, requiring surgical correction after one year of age, or minimal. Isolated patent foramen ovale, isolated patent ductus arteriosus when the only echocardiogram was performed before 21 days of age, and a patent duct in preterm infants were classified as transitional findings and were excluded. Proportions are reported with exact (Clopper-Pearson) 95% confidence intervals and groups were compared using Fisher's exact test. &lt;b&gt;Results:&lt;/b&gt; Among 13,979 live births, 123 infants had an echocardiographically confirmed structural defect of the heart or great vessels detected through screening; a further 39 infants had transitional findings. Postnatal physical examination accounted for 107/123 (87.0%, 95% confidence interval range: 79.7-92.4) of the cases detected by screening; because echocardiography was not performed in screen-negative infants and defects presenting after discharge were not systematically traced, this is the share of screen-detected cases and not the sensitivity of the examination. The second examination at the 48-72 h range accounted for 92/123 (74.8%, 66.2-82.2), including 3 critical and 5 severe defects in which the first examination had shown no abnormality. Prenatal ultrasonography identified 6/16 (37.5%, 15.2-64.6) of critical and severe defects, and 15/123 (12.2%, 7.0-19.3) of all structural defects. The latter figure is not a prenatal detection rate, since there are lesions that cannot be identified before birth. Pulse oximetry screening identified 1/123 (0.8%, 0.0-4.4) after negative prenatal ultrasonography and no clinical signs. The combined protocol detected 123 of the 124 infants known to have a structural defect (99.2%) before discharge; this is a detection rate among known cases. Critical defects were identified in at least 0.50 per 1000 live births and critical plus severe defects in at least 1.14 per 1000; these are lower limits for live births in one centre, not birth prevalence estimates. &lt;b&gt;Interpretations:&lt;/b&gt; Repea","PeriodicalId":16722,"journal":{"name":"Journal of Personalized Medicine","volume":"16 9","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13608021/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149039530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Personalized Sequential Nephron Blockade for Diuretic Resistance in Acute Decompensated Heart Failure: A Narrative Review for the Cardiorenal Clinician.","authors":"Guido Gembillo, Concetto Sessa, Luca Zanoli, Luca Visconti, Maria Federica Ricca, Lorenzo Lo Cicero, Andrea Corsonello, Salvatore Petrina, Antonino Nicosia, Luca Soraci, Giuseppe Fede, Guglielmo Piccione, Sebastiano Lumera, Walter Morale, Domenico Santoro","doi":"10.3390/jpm16090466","DOIUrl":"10.3390/jpm16090466","url":null,"abstract":"<p><p>Heart failure affects more than 64 million people worldwide, and admissions for acute decompensation account for a substantial proportion of cardiovascular healthcare expenditure. Achieving complete decongestion remains the principal objective of inpatient management, yet many patients are discharged with persistent volume overload, a consistent predictor of early rehospitalization and mortality. Loop diuretics have remained the cornerstone of decongestive therapy for more than six decades; however, their effectiveness is frequently limited by diuretic resistance, leaving many patients incompletely decongested despite dose escalation. Diuretic resistance reflects adaptive sodium retention distributed across multiple nephron segments, a process that extends well beyond the loop itself. Distal-tubular-remodeling-enhanced proximal sodium reabsorption, neurohormonal activation, post-diuretic sodium retention, and impaired tubular drug delivery collectively blunt natriuretic responsiveness, explaining why progressive loop-dose escalation often yields diminishing returns. Sequential nephron blockade provides a physiology-based strategy that matches the adjunct agent to the predominant mechanism of sodium retention. We integrate contemporary randomized evidence with renal tubular physiology to propose a mechanism-based approach: acetazolamide for patients with hypochloremic metabolic alkalosis and enhanced proximal sodium reabsorption, thiazide-type diuretics when distal cotransporter escape predominates, vasopressin antagonists for dilutional hyponatremia complicating congestion, and sodium-glucose cotransporter 2 inhibitors as foundational therapy that combines modest acute natriuresis with durable cardiorenal protection. Early assessment of natriuretic response using spot urine sodium further enables individualized treatment escalation. Together, these concepts move sequential nephron blockade beyond empirical combination diuretic therapy toward a mechanism-based strategy for overcoming diuretic resistance. We propose a personalized, phenotype-driven framework in which early urinary sodium response, kidney function, serum chloride, acid-base status, serum sodium, background SGLT2 inhibitor therapy, and venous congestion imaging guide the selection, escalation, and de-escalation of adjunctive therapy, with the goal of more complete and safer decongestion in acute decompensated heart failure. Matching adjunct choice to a patient's individual biochemical phenotype, rather than applying diuretics in a fixed sequence, exemplifies precision medicine applied to acute decongestive therapy.</p>","PeriodicalId":16722,"journal":{"name":"Journal of Personalized Medicine","volume":"16 9","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13608559/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149039425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}