Background/Objectives: Chronic kidney disease (CKD) is a major global public health problem, and conventional biomarkers such as serum creatinine primarily reflect excretory function with limited sensitivity for early detection and for predicting progression. Amino acids (AAs) and acylcarnitines (ACs) reflect metabolic processes related to nitrogen metabolism and mitochondrial fatty-acid oxidation that are influenced by renal function. This study aimed to characterize CKD-associated alterations in AAs and ACs profiles using an integrated analytical framework combining differential analysis, supervised multivariate modeling, differential network enrichment analysis (DNEA), and cross-compartment plasma-urine profiling, moving beyond individual metabolite associations toward a multi-level characterization of CKD-associated metabolic reprogramming. Methods: Plasma and urine samples from 78 patients with CKD and plasma samples from 70 healthy controls were analyzed using flow-injection tandem mass spectrometry (FIA-MS/MS). An integrated targeted metabolomics framework combining differential, multivariate and network-based analyses including DNEA was applied to plasma and paired urine samples to characterize systemic and urinary metabolic alterations in CKD, focusing on AAs and ACs. Results: CKD was characterized by significant elevated short-chain dicarboxylic acylcarnitines, increased methylhistidine (MetHis) and argininosuccinic acid (ASA), together with reduced tryptophan, serine, methionine, and tyrosine in plasma. These metabolites were consistently identified across different analyses and correlated with kidney function markers. DNEA revealed coherent network-level reorganization, with acylcarnitine pathways gaining connectivity and centrality while amino acid modules lost integration in CKD. Cross-compartment analysis identified both systemic and compartment-specific patterns of metabolite distribution. An exploratory clustering-guided biomarker panel combining MetHis, C3DC, and Trp achieved an area under the curve (AUC) of 0.881 for discriminating patients with CKD from controls. Moreover, C6, C8, and C10 remained significantly associated with CKD after additional adjustment for estimated glomerular filtration rate (eGFR). Conclusions: Targeted metabolomic profiling revealed a coordinated metabolic signature in CKD suggesting disturbances in pathways related to fatty-acid oxidation, nitrogen imbalance, and altered amino acid metabolism. Network-level analysis provided evidence of systemic metabolic reorganization beyond individual metabolite changes. As findings derive from an observational cohort with high comorbidity prevalence, the identified signatures should be considered CKD-associated rather than CKD-specific.

Background: Cigarette smoking is a widely recognized risk factor for several diseases and a crucial problem in global health, as it contributes to the development and worsening of various diseases, resulting in an increase in both morbidity and mortality. One of the strategies to reduce the impact of tobacco damage is based on the transition from flammable to non-flammable nicotine products. Objectives: The aim of this narrative review is to summarize the effects of traditional cigarette smoking and non-combustible nicotine products on kidney function. Conclusions: The evidence shows that both combustible and non-combustible nicotine products have harmful effects on kidney health and may promote the onset and progression of kidney dysfunction, leading to chronic kidney disease (CKD).

Background: Constipation in children often presents with non-specific symptoms, which can complicate its recognition in the pediatric emergency department (PED). Aim: This study aimed to characterize the clinical presentations, diagnostic context and testing patterns of children discharged with constipation from a tertiary pediatric emergency center. Methods: A retrospective analysis of medical records of patients under 18 years of age was conducted for patients who presented to the PED of a tertiary hospital in northern Poland from 2021-2024 and were ultimately discharged as K59.0 ICD-10 code (constipation). Demographic data, symptoms reported upon admission, and laboratory and imaging tests performed were collected and reviewed. Results: PED visits discharged with ICD-10 code K59.0 accounted for 2.97% of all 34,278 PED visits during study period. Among 1017 patients discharged with ICD-10 code K59.0, only 26.5% reported constipation as their main complaint. The most common complaints were abdominal pain (61.6%), vomiting (14.4%), and urinary symptoms (4.9%). Commonly suspected initial diagnoses were urinary tract infections or acute appendicitis. More complete documentation of constipation-related symptoms showed an exploratory association with less intensive diagnostic testing. Conclusions: Constipation should be routinely considered in children presenting to the PED with abdominal pain, vomiting, urinary symptoms, or rectal bleeding, even when bowel problems are not the main complaint. Structured history taking supported by simple diagnostic tools could help standardize assessment and support patient selection for further testing, although prospective studies are needed to determine clinical outcomes.

In recent years, Klebsiella pneumoniae (Kpn) has evolved into a global public health threat. Convergent Kpn lineages that are both hypervirulent and multidrug-resistant have emerged and can cause community-acquired, drug-resistant infections, with increased mortality. A major driver of hypervirulence in Kpn is hypermucoviscosity (HMV), a phenotype historically associated with increased capsular polysaccharide (CPS) production. Recent findings show that HMV is a distinct trait characterized by increased CPS chain length and uniformity, rather than by overproduction of CPS. The regulators of mucoid phenotype (RmpADC and/or RmpA2) have traditionally been characterized as determinants of HMV. However, recent evidence suggests that Kpn can also manifest HMV independently of the regulators of mucoid phenotype, driven by missense mutations in the wzc gene of the CPS biosynthesis locus. These findings have immense ramifications, as non-hypervirulent Kpn lineages can rapidly enhance their virulence and invasiveness by acquiring wzc mutations and manifesting HMV. Since HMV confers Kpn with the ability to adhere poorly to immune cells and resist phagocytosis, it enables systemic dissemination. This benefit, however, appears to be niche specific, as HMV hinders adhesion to epithelial cells and biofilm formation on medical devices, traits which may be beneficial in some niches. Kpn tackles this problem by fine-tuning HMV expression via switches driven by mutations or through regulatory control in response to environmental cues. This review synthesizes recent findings on the molecular mechanisms by which HMV is manifested, is intricately regulated, and how HMV contributes to Kpn's success in diverse infection niches, such as the respiratory tract, bloodstream, and urinary tract.

Idiopathic normal pressure hydrocephalus (iNPH) is a common and treatable syndrome related to cerebrospinal fluid circulation disorders in the elderly, with clinical problems including missed diagnosis, misdiagnosis and significant variations in therapeutic efficacy. Therefore, multidisciplinary experts in the Chinese Association for Geriatric Health Care's Hydrocephalus Specialty Branch, the Chinese Medical Association's Neurosurgery Branch, the Chinese Neurosurgery Critical Care Management Collaborative Group, and the Beijing Medical Association's Neurosurgery Branch were organized to formulate the Expert consensus for the diagnosis and treatment of idiopathic normal pressure hydrocephalus (2026 edition). Based on the Chinese expert consensus on the diagnosis and treatment of idiopathic normal pressure hydrocephalu (2016 edition), this consensus systematically reviews relevant literature from January 2016 to June 2025. Combining the findings of comprehensive qualitative analysis and clinical practice, it develops clinical practice recommendations covering epidemiology, pathophysiological mechanisms, diagnosis, assessment, treatment and follow-up. This consensus clarifies the core clinical features, characteristic imaging features, and key auxiliary diagnostic indicators. Comprehensive diagnosis of iNPH requires integration with the results of the cerebrospinal fluid tap test, and differential diagnosis should be made from various neurodegenerative diseases and secondary hydrocephalus. The cerebrospinal fluid tap test is recommended as the core preoperative evaluation tool, with standardized multi-dimensional assessment methods for cognition, urinary function and gaitto match the test. Surgical shunting is confirmed as the current effective treatment, with detailed recommendations on the selection of surgical approaches, shunt system selection and the management of comorbidities, 39 recommendations were finally established. This consensus provides a standardized reference for the clinical diagnosis, assessment and treatment of iNPH. It also highlights future research directions, including early diagnostic biomarkers, minimally invasive surgical techniques and intelligent shunt systems.

Fetal intervention for lower urinary tract obstruction (LUTO) has advanced more slowly than other areas of fetal surgery. Thirteen years after the PLUTO trial, three core problems remain unresolved. Firstly, prenatal ultrasound diagnosis is not accurate enough to reliably distinguish LUTO from non-obstructive megacystis. Secondly, selection criteria for vesico-amniotic shunting (VAS) remain poorly defined, since the developmental impact of bladder outlet obstruction is highly variable between fetuses. Thirdly, outcome reporting is inconsistent, with "perinatal survival" obscuring the true long-term picture for posterior urethral valves (PUV). The introduction of the low-profile SOMATEX© shunt has enabled VAS from as early as 11 weeks' gestation. A recent prospective cohort study (IUS1st) of first-trimester shunting for severe megacystis reported 73% perinatal survival and largely preserved renal function at one year, but also revealed striking urological morbidity, with over half of infants requiring diversion procedures for urethral hypoplasia. Whether this reflects a consequence of urethral bypass throughout gestation, or simply the natural history of the underlying disease, remains unresolved - underscoring the continued need for a control group. Looking ahead, more selective patient stratification may come from combining ultrasound with fetal MRI, fetal urinary peptidomic signatures, and AI-assisted image analysis, while next-generation, pressure-limiting shunts such as the Vortex© device aim to preserve physiological bladder cycling rather than fully defunctionalising the bladder. An international collaborative registry, rather than a further randomised controlled trial, may offer the most realistic route to answering these questions.

Lower urinary tract symptoms (LUTS) and various lower urinary tract dysfunctions (LUTDs) often coexist because their prevalence increases with ageing. In men, benign prostatic obstruction (BPO) is often proposed as a cause of other "secondary" LUTDs. However, causality of BPO in LUTDs, other than voiding LUTS and acute urinary retention, is probably indirect, if present at all. Indirect mechanisms complicate the inference of causality and may reduce the chance of reversibility. BPO is not a unifying explanation for LUTD, but one possible aetiological factor among many age-related, metabolic, neurological, behavioural, and anatomical factors. This mini-review discusses how to evaluate whether associations between BPO and LUTD are causal, reversible, and relevant to treatment decisions. The Bradford Hill viewpoints (strength, consistency, specificity, temporality, biological gradient, plausibility, coherence, experiment, and analogy) remain a useful framework for considering whether observed associations may be causal. However, the potential surgical setting of BPO adds two additional dimensions. First, is BPO needed to maintain the phenotype, such that treating BPO should bring resolution of the secondary problem? Second, if causation appears to apply at a population level, how confidently can that inference be applied to the individual man considering surgery? Association should not be mistaken for causation, causation should not be mistaken for reversibility, and reversibility should not be mistaken for sufficient net benefit for the individual man considering surgery.

Recreational ketamine use is rapidly increasing, and ketamine-induced uropathy (KIU) is gaining recognition for its severe impact on quality of life (QoL), including pain, hematuria, lower urinary tract symptoms (LUTS), and potential negative effects on sexual function. This study investigates the prevalence of sexual dysfunction among men with KIU.

Uropathogenic Escherichia coli (UPEC) strains are the primary cause of urinary tract infections and pose a serious clinical problem due to their remarkable genetic variability, diverse virulence traits, and rapidly increasing antibiotic resistance. In this study, five clinical UPEC isolates (EC3, EC149, EC164, EC179, and EC256) were deeply investigated to better understand their pathogenic potential. The strains differed substantially in genome architecture, mobile genetic elements, plasmid composition, virulence factors composition, and antibiotic resistance profiles, illustrating the highly dynamic nature of UPEC populations. Of particular concern was the detection of plasmids linked to resistance against "last-resort" antibiotics, emphasizing the growing epidemiological risk associated with these pathogens. To address the limitations of conventional therapy, five lytic bacteriophages active against the analyzed UPEC strains were isolated and thoroughly characterized. Comparative genomic and phylogenetic analyses revealed that all phages represent previously undescribed species belonging to the genera Hanrivervirus, Warwickvirus, Nonavirus, Kagunavirus, and Vectrevirus. Functional assays demonstrated pronounced differences in host range and infectivity. Among them, phage vB_EcoS-149_4M emerged as the most promising candidate, combining broad antibacterial activity with high stability and a favourable safety profile, including the absence of toxin or antibiotic resistance genes and no detectable cytotoxicity toward human cell lines. Taken together, these findings highlight both the complexity and clinical threat posed by UPEC strains and the substantial potential of carefully selected bacteriophages as effective and precise antimicrobial tools. In effect, this multi-faceted approach provides a strong foundation for the development of precision phage therapy against multidrug-resistant UPEC infections.

Patient-reported outcome measures (PROMs) complement oncological endpoints by capturing what matters most to patients. The TrueNTH surgical collaboration presented 1-yr PROMs following robotic prostatectomy using accessible visual formats. We present 5-yr PROMs from the phase 3, international PACE-B trial, which randomised men with localised prostate cancer to stereotactic body radiotherapy (SBRT) or conventionally fractionated radiotherapy (CRT). PROMs are reported from baseline to 5 yr and presented using waffle charts to enable visual alignment with surgical outcomes. At 5 yr, urinary incontinence outcomes were favourable and comparable between SBRT and CRT. Leak-free rates were 64% (164/258) for SBRT and 69% (172/249) for CRT, pad-free rates were 91% (233/257) for SBRT and 90% (225/250) for CRT, and moderate or big urinary leakage problems were reported by only 6% (15/250) for SBRT and 4% (9/244) for CRT. Intercourse-adequate erections declined in both groups from baseline to 5 yr: from 35% (133/374) to 17% (43/250) for SBRT, and from 40% (157/391) to 20% (47/240) for CRT. Moderate or big sexual problems increased in both groups, from 24% (87/367) to 31% (74/242) for SBRT and from 22% (85/382) to 32% (77/238) for CRT. Bowel effects were low and comparable between groups, with moderate or big bowel problems reported by 2% (7/397) at baseline and 5% (12/265) for SBRT at 5 yr, and 2% (9/415) at baseline and 5% (13/253) for CRT at 5 yr. Stool incontinence as a moderate or big problem rose from <1% (1/374) to 2% (4/240) in the SBRT group and from <1% (1/395) to 3% (7/238) in the CRT group.

Immune checkpoint inhibitors (ICIs) are increasingly used in oncology and commonly cause thyroid dysfunction. Most patients who develop hypothyroidism after ICI-induced thyroiditis respond to standard weight-based levothyroxine replacement. However, causes of treatment-refractory hypothyroidism are less well recognized in this context. We describe an 81-year-old woman with uterine cancer treated with lenvatinib and pembrolizumab who developed ICI-related thyroiditis with subsequent hypothyroidism. Despite progressive levothyroxine dose escalation to nearly twice the expected weight-based dose, thyroid-stimulating hormone (TSH) remained elevated after normalization of free thyroxine (FT4) and triiodothyronine (T3). Evaluation for malabsorption and nonadherence was unrevealing. Further investigation identified significant proteinuria associated with lenvatinib therapy. Given that thyroid hormone circulates primarily bound to plasma proteins, urinary loss of protein-bound thyroid hormone was suspected to contribute to the increased levothyroxine requirement. Following temporary discontinuation and subsequent dose reduction of lenvatinib, proteinuria improved and thyroid function tests (TFTs) normalized, allowing for a reduction in levothyroxine dose. This case highlights that excessive proteinuria can lead to urinary loss of protein-bound thyroid hormone, resulting in apparent levothyroxine resistance. Clinicians should consider renal losses along with gastrointestinal and medication-related causes when thyroid hormone requirements exceed expected dosing. This is particularly relevant in patients receiving combination cancer therapies that increasingly include ICIs.