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PubMed2026

Bone progression in multiple myeloma: Benefit of zoledronic acid for patients achieving at least Very Good Partial Response and prognostic value of bone turnover markers.

The Magnolia study demonstrated that continuation of zoledronic acid (ZOL) beyond 2 years reduces the risk of progressive bone disease (PBD) in patients with multiple myeloma (MM). This follow-up study investigated the effects of ZOL in patients achieving very good partial response (VGPR) compared to patients who did not and whether bone turnover markers could identify patients at an increased risk of PBD following treatment cessation. Two Magnolia trial subgroups were analysed: patients with VGPR or better after 2 years of ZOL, randomized to either continued treatment or observation, and patients randomized to observation in whom serial bone markers (C-terminal cross-linked telopeptide of type I collagen [CTX], procollagen type I N-terminal propeptide [P1NP], bone-specific alkaline phosphatase [BAP], tartrate-resistant acid phosphatase isoform 5b [TRAcP]) were measured for up to 4 years. Continued monthly ZOL beyond 2 years significantly reduced the risk of PBD (hazard ratio 0.40; 95% confidence interval [CI] 0.16-0.92) in patients with VGPR or better (subgroup 1). After ZOL discontinuation, bone markers increased gradually. Elevated CTX (≥0.30 μg/L) and TRAcP (≥4 U/L) levels were associated with increased 6-month PBD risk (29% and 15% respectively) (subgroup 2). Continuation of ZOL beyond 2 years seems to reduce skeletal progression risk in patients achieving VGPR or better. Elevated CTX or TRAcP levels may help identify patients who could benefit from re-initiating ZOL.

Humans↗

PubMed2026

Association between SGLT2 inhibitors and reporting of phimosis/paraphimosis: a comparative pharmacovigilance analysis of the WHO database.

PURPOSE: Recent data have discussed occurrence of phimosis with Sodium-glucose co-transporter-2 (SGLT2) inhibitors. However, the potential risk among the different SGLT2 inhibitors is unknown. METHODS: Using Individual Case Safety Reports (ICSRs) registered in the WHO pharmacovigilance database (01/01/2000-30/06/2025), comparisons between the different SGLT2 inhibitors and versus other drugs used in diabetes (DUD) were performed. Results are shown as Reporting Odds Ratios (ROR). RESULTS: Among 11 342 810 ICSRs, 227 were phimosis/paraphimosis with SGLT2 inhibitors, mainly between 45 and 64 years. The higher ROR value was found with empagliflozin followed by dapagliflozin and canagliflozin. ROR for SGLT2 inhibitors was higher that of all other DUD [34.72 (25.86-46.62)]. The reporting risk of phimosis/paraphimosis with SGLT2 inhibitors was also higher than that of each pharmacological class of DUD. CONCLUSION: The results suggest an association between SGLT2 inhibitors use and phimosis ICSRs. Empagliflozin had the higher reporting risk.

Humans↗

PubMed2026

Population-level impact of HPV vaccination: a global systematic review of ecological, cross-sectional, and cohort studies.

BACKGROUND: Human papillomavirus (HPV) causes approximately 4.5% of cancers globally, with the highest burden in low- and middle-income countries (LMICs). Since their introduction in 2006, HPV vaccination programs have led to substantial declines in HPV-related outcomes, although impact varies across settings. RESEARCH DESIGN AND METHODS: We conducted a systematic review to evaluate the population-level impact of HPV vaccination on HPV infection, cervical intraepithelial neoplasia grade 2 or higher (CIN2+), genital warts, invasive cervical cancer (ICC), and oropharyngeal cancer (OPC), and examined the influence of coverage, age at initiation, and vaccine type. The review followed PRISMA 2020. RESULTS: Of 13,549 records screened, 63 were included: 9 assessed HPV infection, 24 on CIN2+, 25 on genital warts, and 7 on ICC. Greatest reductions were observed in settings with at least 70% coverage and early vaccination prior to sexual debut, typically achieved through school-based programs. Reported declines ranged from 58-100% for HPV infection, 30-88% for CIN2+, 60-90% for genital warts, and 70-88% for ICC. CONCLUSIONS: HPV vaccination offers strong protection, especially when delivered early and at high coverage within schools. Expanding access and prioritizing underserved populations are essential to achieving global cancer prevention goals. Limitations include heterogeneity across designs, outcome definitions, and follow-up.

Humans↗

PubMed2026

Prevalence and cardiometabolic impact of mild autonomous cortisol secretion in primary aldosteronism: a systematic review and meta-analysis.

Many primary aldosteronism (PA) patients harbor concomitant mild autonomous cortisol secretion (MACS), termed "Connshing syndrome." The prevalence and cardiometabolic impact of this co-secretion have not been quantitatively synthesized. To determine the pooled prevalence of MACS in PA and evaluate its association with cardiovascular (CV) events, type 2 diabetes mellitus (T2DM), and obesity. PubMed, Embase, Cochrane, Web of Science, and Scopus through January 2026. Following PRISMA 2020 and MOOSE guidelines (PROSPERO: CRD420261334965), studies reporting MACS prevalence [post-1 mg dexamethasone suppression test (DST) cortisol ≥1.8 μg/dl] in PA were included. Prevalence was pooled using random-effects models. Odds ratios (ORs) were calculated for cardiometabolic outcomes. Certainty was evaluated using GRADE. Fourteen studies (2356 patients) were included. Pooled MACS prevalence was 26.2% [95% confidence interval (CI): 24.1-28.4; I2 = 24.2%; prediction interval: 21.6-31.4%], consistent across European (27.0%) and East Asian (25.2%) cohorts ( P = 0.62). MACS + PA patients had higher odds of CV events (OR 1.60; 95% CI: 1.07-2.38; P = 0.021) and T2DM (OR 1.37; 95% CI: 1.00-1.86; P = 0.048), but not obesity (OR 1.10; P = 0.411). Sensitivity analyses confirmed robustness. GRADE certainty was moderate for prevalence and low for CV events. Approximately one in four PA patients has MACS, associated with a 60% higher CV event risk. These findings support routine DST screening in PA and have implications for perioperative management and cardiometabolic risk stratification.

Humans↗

PubMed2026

MET expression by immunohistochemistry as a biomarker in pancreatic neuroendocrine tumours.

INTRODUCTION: MET (c-MET) is a receptor tyrosine kinase implicated in numerous cancers, including pancreatic neuroendocrine tumours (pNETs), by promoting cell proliferation, survival, invasion and angiogenesis. Recognizing its oncogenic potential, there is significant interest in MET-targeted therapies for malignancies like pNETs, which often develop treatment resistance. Immunohistochemistry (IHC) has become a practical method for detecting MET overexpression in cancers. This study evaluates MET expression in pNETs by IHC and assesses its correlation with prognostic variables and survival outcomes. METHODS AND RESULTS: Tissue microarrays containing well-differentiated neuroendocrine tumours from the gastrointestinal tract were analysed. The study included 125 pNET cores from 112 patients after application of inclusion criteria. MET expression was determined using the H-score system. Different variables were assessed for H-score distribution and cross-tables. Survival analyses were conducted based on progression-free survival and overall survival. Positive MET expression was found in 83.5% of cases. Higher MET H-scores were seen in patients with lymphovascular invasion (LVI), distant metastases and higher tumour grade (P < 0.05). When assessing different variables for higher MET H-scores, a significant association emerged at the 150-cut-off-point for LVI, perineural invasion, radiological evidence of progression and overall survival. For survival analysis, at a MET H-score threshold of 200, high MET expression was significantly associated with shorter progression-free survival (mean 8.7 versus 13.4 years, P < 0.05) and overall survival (mean 3.6 versus 7.7 years, P < 0.05). CONCLUSION: Elevated MET expression is linked to adverse histopathological features and worse clinical outcomes in pNET. Standardizing MET IHC evaluation is critical as anti-MET therapies develop, and identifying patients likely to benefit from these treatments remains essential.

MET protein↗

PubMed2026

Blood Metabolomic Signatures of 1-Hour Glucose Predict Cardiometabolic Risk.

BACKGROUND: Elevated 1-hour glucose levels during an oral glucose tolerance test strongly predict type 2 diabetes (T2D) and cardiovascular disease. We investigated whether the fasting blood metabolome predicting 1-hour glucose could be a target for improving β-cell function, long-term glycemic trajectories, and reducing the risks of T2D and coronary heart disease. We also investigated whether plasma microRNAs derived from key metabolic organs regulate changes in a metabolomic risk score (MRS) for predicting 1-hour glucose. METHODS: Untargeted blood metabolomics and a frequently sampled 75-g oral glucose tolerance test were performed in participants from the OmniCarb trial (n=162). In an independent weight-loss dietary intervention trial (POUNDS Lost [Preventing Overweight Using Novel Dietary Strategies]), temporal changes in MRS and plasma microRNAs measured by genome-wide sequencing were analyzed. In addition, associations of MRS at baseline and its 10-year changes with long-term risk of incident T2D and coronary heart disease were prospectively investigated in the NHS (Nurses' Health Study). RESULTS: We created a fasting blood MRS for predicting 1-hour glucose (Pearson r=0.8) and found significant associations with half-day (diurnal) postprandial glucose excursions and insulin secretion after 5-week controlled feeding interventions varying in carbohydrate amount and glycemic index. In the POUNDS Lost trial, diet-induced changes in MRSs were related to 2-year trajectories of glucose metabolism; circulating microRNAs regulating cardiometabolic abnormalities were pivotal factors influencing these changes. In the NHS, women in the top 20% of MRS had a multivariate-adjusted relative risk of 3.80 (95% CI, 2.22-6.51) for T2D and 1.48 (95% CI, 1.04-2.12) for coronary heart disease compared with those in the lowest 20%. In addition, 10-year increases in plasma metabolites related to 1-hour glucose were linearly associated with a higher risk of T2D. CONCLUSIONS: Our findings indicate that fasting blood metabolomic signatures predicting elevated 1-hour glucose reflect disease pathophysiology and could be targets for preventing T2D and coronary heart disease.

blood glucose↗

PubMed2026

Prognostic effect of serum glial fibrillary acidic protein and neurofilament light chain for predicting progression independent of relapse activity in multiple sclerosis: A systematic review.

BACKGROUND: Progression independent of relapse activity (PIRA) is increasingly appreciated as one of the important factors contributing to disability accumulation in MS. sGFAP and sNfL could represent markers reflecting two separate biological processes related to relapse-independent progression in MS. OBJECTIVE: To perform a systematic review of the literature on blood GFAP and/or NfL measured in relation to PIRA or other similar relapse-independent progression endpoints in people with MS. METHODS: PubMed, Scopus, and Web of Science databases were searched from inception to 1 June 2026. The eligible studies were original human studies measuring blood GFAP and/or NfL concentrations in serum, plasma, or any other type of blood-derived material and assessing PIRA, PIRMA, CDP/CDW without relapses, relapse-free EDSS progression, non-inflammatory progression, or comparable relapse-independent disability worsening outcomes. Methodological quality was assessed according to the Newcastle-Ottawa scale and the QUIPS instrument for bias detection in the body of evidence on prognostic factors. Due to heterogeneity of outcomes, biomarker measurements and effect estimates, results were synthesized qualitatively rather than quantitatively. RESULTS: After removing duplicates, 1206 records were screened, followed by full-text review of 120 reports. A total of 18 reports were included. Overall, sGFAP was associated more frequently with PIRA or PIRA-like disability progression, particularly in cohorts with suppressed or limited overt inflammatory activity. Evidence for sNfL was more variable and context-dependent: several studies reported associations with PIRA-like or relapse-independent disability worsening when acute inflammatory activity was absent, suppressed, or analytically separated, whereas other studies reported negative or inconclusive findings. Negative or inconclusive results were reported by several articles, particularly when broad outcomes were evaluated or the study population was small. CONCLUSION: Blood GFAP and NfL give complementary but non-interchangeable information concerning PIRA in MS patients. The existing evidence base does not allow us to perform meta-analysis because of heterogeneity in terms of outcomes, standardization of biomarkers, and treatment context. Further prospective investigations with uniform criteria will be necessary for their use as biomarkers of PIRA in clinical settings.

Humans↗

PubMed2026

Construction of an infectious clone of Spodoptera frugiperda densovirus and its biological characteristics.

Densoviruses are highly pathogenic to their insect hosts and have great potential for biocontrol. Spodoptera frugiperda densovirus (SfDV) was isolated from diseased larvae of Spodoptera frugiperda, while its biological functions remain unclear. Herein, we successfully constructed an infectious clone of SfDV. The S. frugiperda larvae transfected with the infectious clone exhibited anorexia, stunted growth, and reduced activity. Histopathological analysis further showed that the epidermis, fat body and trachea were infected instead of muscle and midgut tissues. Transmission electron microscopy (TEM) revealed that numerous virions of about 22 nm were distributed within both the nucleoplasm and cytoplasm of epidermal cells. Moreover, many virions were also found contained within vesicles in the cytoplasm. The replication kinetics of the rescued SfDV (rSfDV) was similar to that of the parental SfDV. The median lethal dose (LD50) and median lethal time (LT50) values of rSfDV were 6.63 × 107 viral genome copies (vgc), 5.23 d, respectively, which were also comparable to those of the parental SfDV. Taken together, the infectious clone of SfDV provides an important tool for further exploring the genome function, pathogenesis, and interactions with its hosts.

Animals↗

PubMed2026

Integrative genomic and transcriptomic analyses identify key regulators of skin pigmentation in Larimichthys crocea.

The yellow body coloration of large yellow croaker (Larimichthys crocea) constitutes a crucial economic trait, yet its underlying genetic regulatory mechanisms remain poorly understood. This study systematically elucidated the molecular basis of body color variation by integrating genome resequencing and skin transcriptome analyses, combined with the contextual analysis of key pigmentation-related genes and phenotypic histological validation. 200 phenotyped individuals (including yellow-selected lines, F1 progeny, and normal control groups, all derived from a well-characterized aquaculture stock) identified 39 significantly associated SNPs (-log₁₀(P) ≥ 6), mapping to multiple candidate genes. These genes were significantly enriched in pathways related to pigment deposition (GO:0033059), melanosome organization (GO:0032438), melanogenesis, and tyrosine metabolism. Cross-developmental stage transcriptome analysis revealed 2395 differentially expressed genes (DEGs). Multi-omics integration identified eight overlapping candidate genes, including tyrp1, slc45a2, oca2, and dgat2, among which tyrp1 was prioritized for in-depth validation based on its core regulatory role in eumelanin synthesis, significant SNP association signal, and consistent downregulation in transcriptomic data. Experimental validation demonstrated that the g.895C > T mutation in exon 2 of tyrp1b was strongly significantly associated with the yellow phenotype: the frequency of mutant genotypes (TT/CT) reached 92.86%in the yellow-selected group, whereas the control group exclusively exhibited the wild-type genotype (CC). qPCR confirmed significantly downregulated tyrp1b expression in the skin of yellow individuals, consistent with the transcriptome trend. Histological and stereomicroscopic observations of skin tissues further validated the physiological basis of the yellow phenotype, revealing a significant reduction in melanophore number and abnormal melanosome morphology in yellow-phenotype individuals, accompanied by increased xanthophore density. These results suggest that tyrp1b mutation is strongly associated with the yellow phenotype. However, the presence of a wild-type CC individual in the yellow group indicates that this mutation is not strictly required for yellow coloration, suggesting that other genetic or environmental factors may also contribute to the phenotype, Additionally, downregulation of the carotenoid metabolism gene bco2 coupled with upregulation of xdh, together with the functional changes of slc45a2 and oca2, may synergistically promote xanthophore pigment deposition, contributing to the yellow phenotype. As melanin synthesis in large yellow croaker relies on the conserved tyrosinase pathway and transporter proteins, mutations in associated genes (tyrp1b, slc45a2, oca2) represent a primary underlying cause for the loss of melanin-based coloration and transition to a yellow phenotype in L. crocea. These findings provide key molecular targets and a theoretical foundation for molecular breeding of body color in this species, and also enrich the understanding of xanthism regulatory mechanisms in teleosts.

Animals↗

PubMed2026

The combined and independent influence of food texture and a 'mindful eating' instruction on eating rate and food intake among Dutch primary schoolchildren.

Eating rate (ER), the amount of food consumed per unit of time, is a key determinant of food intake, with faster ER associated with larger meal size. Research in adults has shown that both sensory properties like texture, and instructions can influence ER and intake. However, their independent and combined effect on ER and intake in children remain poorly understood. This study examined the effects of food texture and a 'mindful eating' instruction on ER and food intake in children. Children (N = 73), 38 boys, aged 4-12 years, participated in a 4-week cluster-randomized incomplete cross-over study conducted during regular school lunches. Using a 2×3 factorial design, children were exposed to two levels of food texture (softer vs. harder whole-grain buns) and three types of instructions (none, control, 'mindful'). Linear mixed models with repeated measures were used, adjusting for sex and group. As the interaction between food-texture and type of instructions was non-significant, it was excluded from the final models. Results revealed a strong main effect of food texture on ER and food intake (all p < 0.001), where compared with softer buns, harder buns were associated with a slower eating rate (Δ = -6.67 g/min, SE = 0.59) and reduced food intake (Δ = -70 g, SE = 8). In contrast, type of instruction had no significant effect on ER or intake (p = 0.85). Our findings demonstrate that food texture exerts a dominant influence on children's eating rate and food intake, highlighting texture modification as a potential leverage point for influencing ER and intake in children.

Humans↗

PubMed2026

Metabolic engineering of Candida yeasts for biotechnological applications.

Candida yeasts represent a versatile yet underexploited platform for industrial biotechnology. These yeasts utilize a remarkably broad range of carbon sources, particularly for hydrophobic carbon sources, coupled with robust growth and diverse biosynthetic capacities, making them promising hosts for sustainable production of chemicals, fuels, and proteins. Despite these advantages, industrial deployment of Candida species has been hindered by concerns regarding opportunistic pathogenicity and the historical lack of efficient genetic manipulation tools, leading to a substantial gap between metabolic potential and practical utilization. Recent advances in functional genomics, genome editing, and systems metabolic engineering are rapidly overcoming these barriers, enabling more precise and efficient strain development. In this review, we systematically summarize recent progress in the metabolic engineering of Candida species as microbial cell factories, with particular emphasis on expanding genetic toolkits, utilizting renewable and non-conventional carbon sources, and biosynthesizing high-value compounds. In addition, we propose a biosafety-oriented classification framework to support their safe industrial deployment. Finally, we discuss current challenges and emerging opportunities, emphasizing that the synergy of synthetic biology and artificial intelligence-driven design holds the key to unlocking the biotechnological potential of Candida yeasts.

Candida↗

PubMed2026

Molecular adaptation of caspase genes to salinity stress in the tropical sea cucumber Stichopus monotuberculatus: A comparative analysis across echinoderms.

Apoptosis is an essential physiological process that plays a critical role in development and tissue homeostasis. Caspases, as central regulators of apoptosis, are crucial in controlling inflammation and cell death. In this study, we investigated the caspase gene family in Stichopus monotuberculatus to explore their potential roles in salinity stress adaptation. Five caspase genes were identified from the genome of S. monotuberculatus, including Smcaspase3, Smcaspase6, Smcaspase8a, Smcaspase8b, and Smcaspase8c. Phylogenetic analysis revealed that these Smcaspase genes clustered into distinct caspase subfamilies and showed high conservation with homologs from other echinoderms and representative vertebrates. Conserved motif and gene structure analyses showed relatively similar structural patterns within each clade, whereas divergence was observed among different subfamilies. Promoter analysis identified numerous cis-acting elements related to gene regulation, immune response, and growth and development. Expression profiling under salinity stress showed that Smcaspase8a was significantly upregulated, particularly under prolonged stress, whereas the other genes exhibited limited transcriptional responses. Our findings highlight caspase function in salinity stress and provide the foundation of molecular salinity adaptation mechanisms in S. monotuberculatus.

Animals↗

PubMed2026

Deciphering CD8+ T cell exhaustion in human cancers through single-cell and spatial transcriptomics.

Exhausted CD8+ T cells (Tex) within the tumor microenvironment (TME) represents a critical barrier limiting anti-tumor immune responses. Tex cells are characterized by upregulated inhibitory immune checkpoint receptors, reduced cytotoxicity, and functional heterogeneity. Their genomic features and regulatory networks remain poorly defined, and only a minority of patients respond to immune checkpoint blockade (ICB) therapy. Single-cell RNA sequencing (scRNA-seq), through high-resolution transcriptomic profiling, has revealed diverse Tex subpopulations, identified subpopulation-specific marker genes and regulatory pathways. Spatial transcriptomics has further mapped the spatial distribution of Tex and their interaction networks with immune cells, tumor cells, and stromal cells, elucidating the impact of spatial heterogeneity on Tex functionality. Current studies indicate that the exhausted state of Tex is dynamic and modifiable, with functional differences among subpopulations closely associated with tumor progression and therapeutic response. However, the genomic characteristics, epigenetic regulation, and spatial interaction mechanisms of Tex require further exploration. This review summarizes recent advances in high-resolution omics technologies for precisely dissecting Tex heterogeneity, functional features, and interactions with other cells. It emphasizes the central value of optimizing Tex-targeted tumor immunotherapy strategies, providing theoretical foundations and directional guidance for developing more effective anti-tumor immunotherapies.

Humans↗

PubMed2026

Emergence of a Novel, Phenotypically Difficult-to-Detect Vancomycin-Resistant Enterococcus faecium Clone (ST117/CT7799).

A significant increase of vancomycin-resistant Enterococcus faecium (VREfm) infections was observed in South-Eastern Austria since 2024. The prolonged outbreak is caused by a novel vanB-VREfm clone (ST117/CT7799, "VREfmstyr"). This study characterizes the atypical difficult-to-detect resistance phenotype and assesses the genomic relatedness of the isolates. Patient and outbreak characteristics were investigated including whole genome sequencing of the isolates. Sensitivity of broth microdilution (BMD), gradient tests (GT), disk diffusion (DD), and automated susceptibility testing (VITEK2) was compared. The performance of commercial screening media was evaluated. From sporadic detections in early 2024 case numbers began to rise during the year. In 30/31 (97%) of all cases, intra-hospital transmission was considered likely and an association with invasive procedures was identified in most cases. Core genome multilocus sequence typing revealed only six allelic differences between VREfmstyr isolates collected in a 12-month period, all belonging to the E. faecium ST117/CT7799 lineage. BMD detected vancomycin resistance (MIC > 4 mg/L) in no more than 16/31 (52%) of isolates after 24 h incubation, while GT and DD misclassified all isolates. Only prolonged incubation improved the performance of these assays. VITEK2 analysis, however, correctly classified all 31 isolates. Of four commercially available VRE-screening agars, only one was capable of detecting VREfmstyr after 24 h incubation. The emergence and clonal dissemination of VREfm ST117/CT7799 reveals a serious diagnostic gap as commonly used diagnostic algorithms fail to reliably detect this resistance phenotype. Our findings should help to further evaluate the true geographical distribution and clinical significance of this novel VREfm clone.

Enterococcus faecium↗

PubMed2026

Early-stage trajectories of social-occupational functioning and long-term functional outcome prediction in early psychosis: A 12-year follow-up of the randomized controlled trial on extended early intervention.

BACKGROUND: Functional impairment in psychosis often persists despite symptomatic remission. There is a paucity of research examining early-course psychosocial functioning trajectories, and none has been conducted to examine relationship between the trajectories and prospective long-term functional outcomes in early psychosis sample. METHODS: We conducted 12-year follow-up of a randomized controlled trial on extended early intervention for first-episode psychosis to identify early-course social-occupational functioning trajectories and their baseline predictors and associations with 12-year outcomes. Participants who completed Social and Occupational Functioning Scale (SOFAS) scores at three or more timepoints between baseline and 3-year follow-up were included in the study. Premorbid adjustment, illness characteristics, symptom severity, functioning, and treatment profiles were assessed. Latent growth mixture modeling was employed to derive early-course social-occupational functioning trajectories based on SOFAS scores over 3-year follow-up. RESULTS: A total of 148 participants were included in this study, with 106 patients having completed the 12-year follow-up. Our results identified four distinct trajectories, including persistently-good class, gradually-improved class, suboptimal-stable class, and persistently-poor class. Patients in persistently-poor class had more severe negative symptoms at baseline compared to patients in persistently-good class. Patients with persistently-poor trajectory had worse long-term outcomes than those with other classes in the majority of functional measures at 12-year follow-up. CONCLUSIONS: The majority of patients were classified in early-stage suboptimal or poor functional trajectories. Above one-fourth of the participants exhibited persistently-poor social-occupational functioning trajectory, which predicted worse functional outcomes at 12-year follow-up. These findings highlighted the importance of tracking functional changes during the initial years of illness.

Humans↗

PubMed2026

Comparison of VCV and PCV-VG modes on diaphragmatic function in diabetic patients undergoing laparoscopic colorectal surgery: a prospective randomized controlled study.

BACKGROUND: Diabetic patients are prone to induce diaphragmatic weakness, which can lead to postoperative pulmonary complications (PPCs). The optimal mechanical ventilation mode may potentially improve postoperative diaphragmatic function. This study evaluates the effects of two ventilation modes under driving pressure-guided ventilation strategy on diaphragmatic function, as assessed by diaphragm thickening fraction (DTF) and diaphragm excursion (DE), in diabetic patients following laparoscopic colorectal surgery. METHODS: Eighty patients diagnosed with Type II diabetes scheduled for elective laparoscopic colorectal surgery, were randomly allocated to either the pressure-controlled volume-guaranteed ventilation (PCV-VG) group (Group P) or the volume-controlled ventilation (VCV) group (Group V) during surgery. The primary outcome was diaphragmatic function assessed during both tidal breathing and maximal inspiratory effort after surgery. Secondary outcomes included intraoperative mechanical power, PPCs, and other complications. RESULTS: A total of eighty patients were included in the final analysis. The averaged area under the curve (AUC) for mechanical power during ventilation was significantly lower in Group P than in Group V (p = 0.002). PCV-VG significantly improved both DE and DTF within the first two days post-surgery (AUCDEtidal: p = 0.088, AUCDTFtidal: p = 0.004, AUCDEmax: p = 0.029, AUCDTFmax: p = 0.017). Postoperative diaphragmatic weakness was less frequent in Group P than in Group V (p = 0.019). However, there was no difference in the incidence of PPCs between the two groups (p = 0.155). CONCLUSION: PCV-VG mode can reduce intraoperative mechanical power, better preserve postoperative diaphragmatic function. However, these improvements did not translate into clinical benefits, as evidenced by the lack of reduction in the incidence of PPCs.

Humans↗

PubMed2026

Phase 1 Study Evaluating Gefurulimab Pharmacokinetics and Safety Following Delivery Via Autoinjector or Prefilled Syringe With Needle Safety Device in Healthy Adults.

PURPOSE: Gefurulimab, a novel dual-binding nanobody targeting complement component 5 (C5), is in clinical development for anti-acetylcholine receptor antibody-positive generalized myasthenia gravis. Gefurulimab has a low molecular weight, enabling subcutaneous (SC) self-administration by autoinjector (AI) or prefilled syringe with needle safety device (PFS-SD). We compared gefurulimab pharmacokinetic (PK) exposure and safety in healthy adults following a single SC dose administered by AI versus PFS-SD. METHODS: In this phase 1, open-label, randomized, parallel-group study (NCT06208488), healthy participants aged 18 to 65 years were stratified by weight and randomized equally to 1 of 6 combination groups of device and injection site (abdomen/thigh/upper arm). Participants received a single SC dose of gefurulimab on day 1 and were assessed throughout the 92-day evaluation period. Primary endpoints were PK parameters for each device: maximum observed concentration (Cmax) and area under the serum concentration-time curve (AUCinf, AUClast). PK across injection sites, pharmacodynamics, safety, immunogenicity, and device performance were also assessed. FINDINGS: Overall, 175 participants were randomized: AI (n = 87), PFS-SD (n = 88). Geometric least squares mean ratios (90% CI) comparing AI/PFS-SD for Cmax, AUCinf, and AUClast were 97.6% (94.5-100.8), 99.6% (96.1-103.3), and 98.8% (95.2‒102.6), respectively. Secondary analyses found no meaningful differences in PK parameters across injection sites. Serum-free C5 concentrations over time, treatment-emergent adverse event (TEAE) profiles, and antidrug antibody responses were similar between cohorts. Most TEAEs were mild; none led to study discontinuation. IMPLICATIONS: SC administration of gefurulimab by AI and PFS-SD was well tolerated with comparable exposure, meeting bioequivalence criteria.

Humans↗

PubMed2026

Risk factors associated with urinary tract infection within 4 days of male rectal cancer surgery in the era of enhanced recovery after surgery (ERAS) programs.

BACKGROUND: Bladder drainage is systematically used in rectal cancer surgery in male patients, even in the era of enhanced recovery after surgery (ERAS). However, little data is available on risk factors for urinary tract infection (UTI). Identifying the risk factors associated with UTI within 4 days of male rectal cancer surgery in an ERAS program could support more individualized decision-making. METHODS: We used data from the GRECCAR 10 randomized clinical trial, a comparison of outcomes of transurethral catheterization (TUC) or suprapubic catheterization (SPC). 240 patients were randomized, 209 retained in the study (TUC n = 99; SPC n = 109). Univariate and multivariate logistic regression post-hoc study analyses were performed to assess association between potential predictive factors and UTI within 30 days after surgery. RESULTS: Out of 208 patients (median age 64.5 years), 19 (9.1%) had UTI, 26 (12.5%) had bacteriuria and 145 (69.7%) had pyuria. Univariate analysis identified age ≥ 65 years (OR = 3.08 [1.07-8.89]; p = 0.038), hypertension (OR = 3.65 [1.23-10.84]; p = 0.020) and ASA score ≥ 3 (OR = 4.15 [1.53-11.2]; p = 0.005) as risk factors for UTI until POD4. Multivariate analysis identified ASA score ≥ 3 with a risk of UTI. CONCLUSION: Regarding male rectal cancer surgery, our study shows that nearly 1 in 10 patients had UTI within 4 days. An ASA score ≥ 3 is an independent risk factor linked to UTI. Identifying this risk factor for UTI is necessary to advise patients, support a tailored decision-making process, and prevent these complications.

Humans↗