A Nationwide, Population-Based, Study In Italy

[Posted 22/May/2023]

AUDIENCE: Family Medicine

KEY FINDINGS: The findings suggest that primary care databases may be used to enhance the early identification of SMA. Additional efforts are needed to exploit the electronic health records of general practitioners to allow early recognition of SMA.

BACKGROUND: Spinal muscular atrophy (SMA) is a rare genetic disease with a broad spectrum of severity. Although an early diagnosis of SMA is crucial to allow proper management of patients, the diagnostic delay is still an issue. Therefore, this study aimed to investigate the clinical correlates of SMA among primary care patients.

DETAILS: The Health Search Database (HSD) was adopted. To estimate the prevalence and incidence rate of SMA, a cohort study was conducted on the population (aged >=6 years) being registered in HSD from 1 January 2000 up to 31 December 2019. To investigate the clinical correlates of SMA, a nested case-control study was performed. SMA cases have been classified according to a clinically based iterative process as "certain", "probable" or "possible". To test the association between clinical correlates and SMA cases a multivariate conditional logistic regression model was estimated. The SMA prevalence combining "certain", "probable" and "possible" cases was 5.1 per 100,000 in 2019 (i.e. 1.12 per 100,000 when limited to "certain" cases), while the yearly incidence rate ranged from 0.12 to 0.56 cases per 100,000. Comparing "certain" cases with matched controls, the presence of neurology visits (OR = 6.5; 95% CI: 1.6-25.6) and prescription of electromyography (OR = 4.6; 95% CI: 1.1-18.7) were associated with higher odds of SMA diagnosis.

Copyright © The Authors. Oxford University Press. All rights reserved.

Source: Maggi, L., Vita, G., Marconi, E., et al. (2023). Opportunities For An Early Recognition Of Spinal Muscular Atrophy In Primary Care: A Nationwide, Population-Based, Study In Italy. Family Practice. 2023; 40(2): 308-313. Published: April, 2023. DOI: 10.1093/fampra/cmac091.

A Meta-Analysis

[Posted 9/Dec/2025]

AUDIENCE: Endocrinology, Nephrology

KEY FINDINGS: Within the studied participants, there were clear absolute benefits of SGLT2 inhibitors on kidney, hospitalization, and mortality outcomes irrespective of diabetes status and level of UACR.

BACKGROUND: There is uncertainty about the effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors in participants with chronic kidney disease, with guidelines offering different strengths of recommendation based on diabetes status and urine albumin to creatinine ratio (UACR). Study was conducted to assess the relative and absolute effects of SGLT2 inhibitor use across efficacy and serious safety outcomes in participants stratified by diabetes status and UACR (>=200 mg/g or <200 mg/g). Included 8 randomized clinical trials that studied an SGLT2 inhibitor with a label indication for use in kidney disease and recorded longitudinal kidney outcomes and baseline data on albuminuria. Assessed the effects of SGLT2 inhibitor use on clinical efficacy and safety outcomes. Heterogeneity by baseline level of UACR was assessed separately by diabetes status.

DETAILS: A total of 58,816 participants (mean age, 64 [SD, 10] years; 35% were female; 48,946 with diabetes and 9870 without diabetes) were included from trials comparing an SGLT2 inhibitor vs placebo. Allocation to an SGLT2 inhibitor produced a lower rate of kidney disease progression (33 vs 48 for placebo per 1000 patient-years; hazard ratio [HR], 0.65 [95% CI, 0.60-0.70] in those with diabetes and 32 vs 46 per 1000; HR, 0.74 [95% CI, 0.63-0.85] in those without diabetes), a lower rate of acute kidney injury (14 vs 18 per 1000 [HR, 0.77; 95% CI, 0.69-0.87] with diabetes and 13 vs 18 per 1000 [HR, 0.72; 95% CI, 0.56-0.92] without diabetes), a lower rate of any hospitalization (202 vs 231 per 1000 [HR, 0.90; 95% CI, 0.87-0.92] with diabetes and 203 vs 237 per 1000 [HR, 0.89; 95% CI, 0.83-0.95] without diabetes), and a lower rate of any death (42 vs 47 per 1000 [HR, 0.86; 95% CI, 0.80-0.91] with diabetes and 42 vs 48 per 1000 [HR, 0.91; 95% CI, 0.78-1.05] without diabetes). Diabetes-specific HRs were similar in participants (with a UACR >=200 mg/g vs with a UACR <200 mg/g) considered separately. Higher absolute risk at a UACR of 200 mg/g or greater meant larger estimated absolute benefits on kidney disease progression were evident in this subgroup. Clear absolute benefits were evident for other efficacy outcomes, and particularly hospitalization, in participants with a UACR less than 200 mg/g. Net absolute benefits remained in the analyses of non–heart failure populations and when estimated glomerular filtration rate was less than 60 mL/min/1.73 m2.

Copyright © American Medical Association. All Rights Reserved.

Source: Staplin, N., Roddick, A. J., Neuen, B. L., et al. Effects of Sodium Glucose Cotransporter 2 Inhibitors by Diabetes Status and Level of Albuminuria: A Meta-Analysis. JAMA. . 2025; Published online: November 7, 2025. DOI: 10.1001/jama.2025.20835.

[Posted 11/Nov/2025]

AUDIENCE: Ob/Gyn, Cardiology

KEY FINDINGS: Overall, prenatal fine particulate matter exposure induces excessive inflammation and oxidative stress in paraventricular nucleus microglia through the Nrf2/NLRP3 signaling pathway, resulting in central and peripheral sympathetic overactivation, leading to hypertension and left ventricular hypertrophy.

BACKGROUND: Adverse factors during pregnancy can significantly increase the incidence of hypertension in adult offspring. Activation of the sympathetic nervous system is closely associated with the development and progression of hypertension.

DETAILS: Authors established a model of offspring hypertension induced by prenatal fine particulate matter exposure to evaluate the role of the sympathetic nervous system activation. Quantitative immunofluorescence and Western blot analysis were used to assess the levels of activated and inhibitory sympathetic neurons. The effects of the central and peripheral sympathetic nervous systems were evaluated using clonidine and renal sympathetic denervation. In addition, the activation of microglia in the lateral ventricle region and the expression of the Nrf2 (nuclear factor E2-related factor)/ NLRP3 (NLR family pyrin domain-containing 3) signaling pathway were analyzed. The adult offspring showed increased neuronal hyperactivity and sympathetic nervous system activity. Specific inhibition of the central sympathetic nervous system and renal denervation effectively reversed the prenatal fine particulate matter-induced blood pressure elevation in adult offspring. In addition, overactivation of oxidative stress and microglia-mediated inflammation in the paraventricular nucleus was responsible for increased central sympathetic activity in the adult offspring exposed to prenatal fine particulate matter. Furthermore, authors confirmed the critical role of the Nrf2/NLRP3 signaling pathway in oxidative stress and inflammation activation in the paraventricular nucleus of adult offspring.

Copyright © American Heart Association, Inc. All rights reserved.

Source: Zhang, X., Yang, B., Li, M., et al. Prenatal PM2.5 Exposure Induces Offspring c via Nrf2/NLRP3 Pathway. Hypertension. 2025; 82(11): 1841-1843), Published: November, 2025. DOI: 10.1161/HYPERTENSIONAHA.125.2487.

Secondary Analysis of DRIGITAT Study

[Posted 5/Nov/2025]

AUDIENCE: Ob/Gyn, Family Medicine

KEY FINDINGS: In a SGA population, maternal BMI, gestational age, EFW and sFlt-1/PlGF ratio at inclusion, highest UCR at any time, development of pre-eclampsia and fetal growth velocity were associated with CAPO. A model incorporating EFW at inclusion, sFlt-1/PlGF ratio at inclusion and highest UCR was most effective for the prediction of CAPO.

BACKGROUND: Purpose of this study is to evaluate the predictive value of markers of placental insufficiency and fetal growth restriction for a composite adverse perinatal outcome (CAPO) in a small-for-gestational-age (SGA) population. Authors also aimed to identify profiles that discriminate fetuses as low or high risk for CAPO, and to evaluate the association of onset of labor and mode of birth with CAPO.

DETAILS: This was a preplanned post-hoc analysis of the DRIGITAT study, a Dutch multicenter cohort study of management strategy in 690 singleton SGA pregnancies at 32.0-36.9 weeks' gestation, between 2018 and 2022. Authors used data from 440 participants with available biomarker measurements, who were not randomized for immediate birth before 36 weeks' gestation on the basis of recurrent abnormal Doppler velocimetry. Authors defined CAPO as fetal death, adverse condition at birth, major neonatal morbidity and/or neonatal mortality. Authorse analyzed the predictive value for CAPO of maternal body mass index (BMI), gestational age, estimated fetal weight (EFW) and soluble fms-like tyrosine kinase-1 to placental growth factor ratio (sFlt-1/PlGF ratio) at inclusion, development of pre-eclampsia, highest value of the umbilicocerebral ratio (UCR) and fetal growth velocity. Authors also used these variables to develop a prediction model for CAPO using forward stepwise logistic regression to emulate real-world clinical evaluation. In this population of 440 singleton SGA pregnancies, maternal BMI at inclusion (P = 0.02), gestational age at inclusion (P <= 0.001), EFW at inclusion (P <= 0.001), sFlt-1/PlGF ratio at inclusion (P <= 0.001), development of pre-eclampsia (P <= 0.001), highest value of the UCR measured at any time during pregnancy (P <= 0.001) and fetal growth velocity (P <= 0.001) were all associated significantly with CAPO. When combined into a prediction model using logistic regression analysis, maternal BMI at inclusion, gestational age at inclusion, development of pre-eclampsia and fetal growth velocity did not add to the predictive value of the model, because of their correlation with other variables. The area under the receiver-operating-characteristics curve of the final prediction model, comprising EFW at inclusion, sFlt-1/PlGF ratio at inclusion and the highest UCR value at any time, was 0.75 (95% CI, 0.70–0.81). At false-positive rates of 5%, 10% and 25%, the sensitivities of the prediction model for CAPO were 35.6%, 44.2% and 63.5%, respectively. The median gestational age at birth and birth weight were lower in neonates that experienced CAPO compared with those that did not (37.0 weeks vs 38.3 weeks and 1.993 kg vs 2.518 kg, respectively). Vaginal birth occurred in 69.3% of our population. In the group that experienced CAPO, a higher number of (emergency) Cesarean sections were performed.

Copyright © The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. All rights reserved

Source: Kamphof, H. D., Marijnen, M. C., Damhuis, S. E., et al. Predictive Value of Fetal Doppler Velocimetry, Fetal Growth Trajectory and Maternal Serum Biomarkers for Short-Term Adverse Perinatal Outcome: Secondary Analysis of DRIGITAT Study. Ultrasound in Obstetrics & Gynecology. 2025; 66(4): 470-470. Published: October, 2025. DOI: 10.1002/uog.29266.

[Posted 4/Nov/2025]

AUDIENCE: Oncology, Gastroenterology

KEY FINDINGS: In the phase II Pancreatic Adenocarcinoma Signature Stratification for Treatment-01 (PASS-01) trial population, PFS was similar between GnP and mFFX; however, OS and safety trends favored GnP. The second-line setting appears inadequate to offer precision choices, given the short survival observed.

BACKGROUND: Goal of this study is to assess modified folinic acid/leucovorin, fluorouracil, irinotecan, oxaliplatin (FOLFIRINOX [mFFX]) versus gemcitabine/nab-paclitaxel (GnP) in de novo metastatic pancreatic ductal adenocarcinoma (PDAC) and explore predictive biomarkers.

DETAILS: Patients were randomly assigned 1:1 to mFFX or GnP with exclusion of germline pathogenic variants in BRCA1/2 or PALB2. The primary end point was progression-free survival (PFS) between arms with 0.3 significance. The per-protocol (PP) population included patients who received one dose of chemotherapy. Pretreatment biopsies underwent whole-genome/transcriptome sequencing and patient-derived organoid (PDO) development, providing correlate recommendations at a molecular tumor board and outcomes assessed according to RNA signatures (basal-like v classical). Of 160 patients randomly assigned (80 mFFX, 80 GnP), 140 patients were in the PP population (71 mFFX, 69 GnP), with median follow-up of 8.3 months. The median PFS was 4.0 months for mFFX versus 5.3 months for GnP (hazard ratio [HR], 1.37 [95% CI, 0.97 to 1.92]; P = .069) in intention-to-treat. Median overall survival (OS) was 8.5 months with mFFX and 9.7 months with GnP (HR, 1.57 [95% CI, 1.08 to 2.28]; P = .017). Genomic data were generated in 94%, transcriptomes in 74%, and PDOs in 50%. The median PFS for those with basal-like was 3.0 (mFFX) and 5.5 (GnP) months (P = .17), and classical PDAC was 6.3 (mFFX) versus 5.4 (GnP) months (P = .36). The median OS in basal-like was 7.5 (mFFX) and 8.9 (GnP) months (P = .75) versus in classical OS was 9.7 (mFFX) and 13.9 (GnP) months (P = .047). Overall, 75 (54%) of patients received second-line treatment, 33/75 (44%) correlate-guided. The median time on second-line treatment was only 2.1 months with a median OS of 5.4 months for a correlate-guided choice versus 4.4 months on a standard chemotherapy approach (P = .45).

Copyright © American Society of Clinical Oncology. All rights reserved.

Source: Knox, J. J., O'Kane, G., King, D., et al. PASS-01: Randomized Phase II Trial of Modified FOLFIRINOX Versus Gemcitabine/Nab-Paclitaxel and Molecular Correlatives for Previously Untreated Metastatic Pancreatic Cancer. Journal of Clinical Oncology. 2025; 43(31):3325. Published: November, 2025. DOI: 10.1200/JCO-25-004.

[Posted 3/Nov/2025]

AUDIENCE: Internal Medicine, Cardiology

KEY FINDINGS: HDL_Lox levels are highest in patients with ACS. Patients with stable CAD have higher levels than healthy controls. Correspondingly, the parameters of HDL function measured in this study, which all indicate a loss of HDL's atheroprotective function, correlate with these findings. Our study establishes a novel mechanistic pathway linking oxidized HDL to the presence of an ACS.

BACKGROUND: High-density lipoprotein (HDL) function, rather than its concentration, plays a crucial role in the development of coronary artery disease (CAD). Diminished HDL antioxidant properties, indicated by elevated oxidized HDL (nHDL_Lox) and diminished paraoxonase-1 (PON-1) activity, may contribute to vascular dysfunction and inflammation. Data on these associations in CAD patients, including acute coronary syndrome (ACS), remain limited. The aim of this study is to assess the association of oxidized HDL with PON-1 activity, oxidized low-density lipoprotein (LDL), vascular cell adhesion molecule-1 (VCAM-1), IL-6 levels, and nitric oxide (NO) production as markers of vascular health.

DETAILS: Authors assessed HDL function in three groups: 90 CAD patients, 90 healthy controls, and 90 ACS patients. HDL antioxidant function was measured using a validated biochemical assay to quantify oxidized HDL (nHD_Lox). Plasma PON-1 activity, oxidized LDL, VCAM-1, IL-6, and NO production were also evaluated. ACS patients had nHDL_Lox levels 140% higher than healthy controls (p < 0.001). Higher nHDLox levels were significantly linked to vascular inflammation, reflected by elevated VCAM-1 levels. Additionally, a reduced PON-1 activity indicates an impaired antioxidant protection in ACS patients. Finally, oxidized LDL levels were elevated, and NO production was reduced, suggesting impaired vascular function.

Copyright © John Wiley & Sons, Inc. All rights reserved

Source: Sasko, B., Pagonas, N., Christ, M., et al. Oxidized High-Density Lipoprotein Associates with Cardiometabolic Dysfunction in Coronary Artery Disease and Acute Coronary Syndrome. Journal of Internal Medicine. 2025; 298(5): 464-477. Published: November, 2025. DOI: 10.1111/joim.70019.