Treatment Options Research Articles

PSMA-PET/CT response after metastasis-directed radiotherapy of bone oligometastases in prostate cancer.

Bone metastases are very common in advanced prostate cancer and can sensitively be detected utilizing PSMA-PET/CT. Therefore, our goal was to evaluate the suitability of PSMA-PET/CT-guided metastasis-directed external beam radiotherapy (MDT) as treatment option for patients with biochemical recurrence and oligometastatic bone lesions. We retrospectively examined 32 prostate cancer patients with biochemical recurrence and PSMA-positive oligometastatic disease limited to the bone (n = 1-3). A total of 49 bone lesions were treated with MDT. All patients received a post-radiotherapy PSMA-PET/CT-Scan. Changes in SUVmax, PSMA-positive tumor volume per lesion and PSA, as well as the correlation between the PET/CT-interval and SUVmax response were calculated. MDT lead to a SUVmax decrease in 46/49 (94%) of the lesions. The median relative decline of SUVmax was 60.4%, respectively. Based on PSMA-positive lesion volume with a SUV cut-off of 4, 46/49 (94%) of lesions showed complete response, two (4%) partial response and one lesion (2%) was stable on PSMA-PET/CT after MDT. Most of the treated patients (56.3%) showed an initial PSA decline at three months and a PSA nadir of median 0.14 ng/ml after a median time of 3.6 months after MDT. The median relative PSA change at three months after MDT was 3.9%. MDT is a very effective treatment modality for prostate cancer bone oligometastases and lesion response to MDT can be assessed using the (semi-)quantitative parameters SUVmax and PSMA-positive lesion volume with established SUV cut-offs.

Stage IC grade 1 endometrioid adenocarcinoma of the ovary: assessment of post-operative chemotherapy de-escalation

ObjectiveGiven limited real-world practice data evaluating the National Comprehensive Cancer Network clinical practice guidelines for possible post-operative chemotherapy omission as a treatment option for patients with stage IC grade 1...

New Endoscopic Devices and Techniques for the Management of Post-Sleeve Gastrectomy Fistula and Gastric Band Migration.

Post-sleeve gastrectomy fistulas are a rare but possibly severe life-threatening complication. Besides early reoperation and drainage, endoscopy is the main treatment option. According to the clinical setting, endoscopic treatment options comprise stent or clip placement. New endoscopic therapies have recently gained attention, including endoscopic vacuum therapy, VacStent therapy, endoscopic internal drainage with pigtail stents, endoscopic suturing and stem cell injection. In this narrative review, we shed light on recent literature, developments, indications and contraindications of these treatments. Intragastric gastric band migration is a rare complication after gastric band positioning. Reoperation can sometimes be difficult, especially when a gastric band has already migrated far into the stomach. Endoscopic retrieval can be a valid, non-invasive therapeutic solution. We reviewed the current literature on this matter.

Prognostic Nomogram Predicting Survival and Propensity Score Matching with Demographics and Comparative Analysis of Prostate Small Cell and Large Cell Neuroendocrine Carcinoma.

Background: This retrospective study aims to examine the patient demographics, survival rates, and treatment methods for small-cell neuroendocrine carcinoma (SCNEC) and large-cell neuroendocrine carcinoma (LCNEC) of prostate origin while also identifying the main differences between common types of prostate cancer with comparative analysis for survival. Methods: Our analysis utilized the Surveillance, Epidemiology, and End Results database (SEER), and data was collected from 2000-2020. Cox proportional hazards and chi-squared analysis were used for statistical analysis. Results: A total of 718 cases of prostate small and large neuroendocrine carcinoma were identified. The median age was 71.5 years, and the median follow-up was 11.0 years (95% confidence interval (95% CI) = 9.2-12.8). Most patients were over the age of 80 years (33.8%) and Caucasian (74.4%). The overall 5-year survival was 8.0% (95% CI = 6.8-9.2). The 5-year OS for Caucasians was 7.3% (95% C.I. 6.0-8.3). For Black Americans, the 5-year OS was 11.9% (95% C.I. 7.3-16.5). For Hispanics, the 5-year OS was 12.2% (95% C.I. 7.7-16.7). The 5-year cause-specific survival (CSS) was 16.2% (95% CI = 14.3-18.1). For treatment modality, the five-year survival for each were as follows: chemotherapy, 3.5% (95% CI = 2.1-4.9); surgery, 18.2% (95% CI = 13.6-22.8); multimodality therapy (surgery and chemotherapy), 4.8% (95% CI = 1.7-7.9); and combination (chemoradiation with surgery), 5.0% (95% CI = 1.0-9.0). The prognostic nomogram created to predict patient survivability matched the findings from the statistical analysis with a statistical difference found in race, income, housing, stage, and nodal status. The nomogram also indicated a slight increase in mortality with tumors of greater size. This analysis showed a slight increase in mortality for patients of Asian race. In addition, there was a significant increase in death for patients with stage 3 tumors, as well as patients who underwent surgery and radiation. Furthermore, we performed propensity score matching for survival differences, and no survival difference was found between SCNEC and LCNEC. Conclusions: Asian patients, larger tumor size, and distant disease were associated with worse long-term clinical outcomes. By leveraging insights from registry-based studies, clinicians can better strategize treatment options, improving patient outcomes in this challenging oncology arena.

Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors as a New Treatment Option for Anemia in Chronic Kidney Disease.

Anemia plays an important role in chronic kidney disease (CKD) progression because it worsens the quality of life and increases the risk of cardiovascular complications in CKD patients. In such cases, anemia is mainly caused by endogenous erythropoietin (EPO) and iron deficiencies. Therefore, KDIGO and ERBP guidelines for anemia treatment in CKD patients focus on recombinant EPO and iron supplementation. A recent new treatment option for anemia in CKD patients involves blocking the hypoxia-inducible factor (HIF) system with prolyl hydroxylase inhibitors (PHIs), what causes increasing endogenous EPO production and optimizing the use of iron. Clinical studies have shown that the hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) covered in this manuscript-roxadustat, vadadustat, daprodustat, and molidustat-effectively increase hemoglobin (Hb) levels in both non-dialyzed and dialyzed CKD patients. Moreover, these medicines reduce blood lipid levels and do not accelerate CKD progression. However, blockage of the HIF system by HIF-PHIs may be associated with adverse effects such as cardiovascular complications, tumorogenesis, hyperkalemia. and retinopathy. More extensive and long-term clinical trials of HIF-PHIs-based anemia treatment in CKD patients are needed, and their results will indicate whether HIF-PHIs represent an effective and safe alternative to EPO and iron supplementation for anemia treatment in CKD patients.

A side-by-side comparison of fine-tuning options for treatment of medically refractory epilepsy: Antiseizure medications, vagus nerve stimulation and ketogenic diet therapies.

There are many treatment options available for patients with medically refractory epilepsy including antiseizure medications, surgery, devices and ketogenic diet therapy. Ketogenic diet therapy has been shown to be a safe and effective treatment option in adult and pediatric patients. In order to obtain maximal clinical effectiveness and tolerability of any treatment option, adjustments are often necessary. This article outlines the “fine tuning” options available for antiseizure medications, vagus nerve stimulation and ketogenic diet therapies and demonstrates that ketogenic diet therapies offer a wider array of personalizing and fine-tuning options.

T cell-related circRNA pairs to predict prognosis of patients with esophageal squamous cell carcinoma

The prognosis for esophageal squamous cell carcinoma (ESCC), a prevalent and aggressive form of cancer, remains poor despite advancements in treatment options. Addressing the gap in comprehensive prognostic information derived from circRNA expression profiles for ESCC, our study aimed to establish a linkage between circRNA expressions and ESCC prognosis. To achieve this, we first developed an optimized prognostic model named T cell-related risk score (TRRS), which integrates T cell-associated features with machine learning algorithms. In parallel, we re-analyzed existing RNA-seq datasets to redefine the expression profiles of circRNAs and mRNAs. Utilizing the TRRS as a foundational “bridge,” we identified circRNAs correlated with TRRS, leading to the development of a novel circRNA pair-based prognostic model, the TCRS, which is independent of specific expression levels. Further investigations uncovered two circRNAs, circNLK(5,6,7).1 and circRC3H1(2).1, with potential functional significance. These findings underscore the utility of these risk scores as tools for predicting overall survival and identifying potential therapeutic targets for ESCC patients.

Construction of a prognostic model for colon cancer by combining endoplasmic reticulum stress responsive genes

Endoplasmic reticulum stress may affect the occurrence and development of cancer. However, its effect on the prognosis of colon cancer (CC) patients is not clear yet. Herein, based on TCGA database, we screened 15 endoplasmic reticulum stress responsive genes (ERSRGs) associated with the prognosis of CC patients by Cox regression. By LASSO and multivariate Cox regression analyses, a prognostic risk assessment model involving 12 genes (DNAJB2, EIF4A1, YPEL4, COQ10A, IRX3, ASPHD1, NTRK2, TRIM39, XBP1, GRIN2B, LRRC59, and RORC) was built. The survival curves indicated that patients in the low-risk group had good prognosis. ROC curves demonstrated a good performance of this 12-gene prognostic model, and the Riskscore could be considered as an independent prognostic factor. Patients in low-risk group benefit more from immune checkpoint inhibitor and immune checkpoint blockade (ICB) treatment. Besides, the enrichment analysis suggested a remarkable difference in Ca2+ signaling in both groups. Finally, based on the cMAP database, we identified several potential drugs that could target high-risk groups, such as Dasatinib, GNF-2, Saracatinib, and WZ-1-84. To sum up, our research constructed an ERSRGs-characteristic prognostic model. The model is a promising biomarker for prediction of clinical outcomes and immune therapy response of CC patients. SignificanceBased on the transcriptomic data of colon cancer in the TCGA database, this study screens 12 endoplasmic reticulum stress-related genes (ERSRGs), including DNAJB2, EIF4A1, YPEL4, COQ10A, IRX3, ASPHD1, NTRK2, TRIM39, XBP1, asphD1, NTRK2. GRIN2B, LRRC59, and RORC, and a prognostic model was constructed. This model can be used as a predictor of prognosis and immunotherapy response in colon cancer patients. At the same time, model-based prediction of drugs can also be a potential option for colon cancer treatment in the future.

Bioresponsive hydroxyethyl starch-flurbiprofen nanoparticles targeted to inflammatory microenvironments for post-operative pain management

Post-operative pain can hinder post-operative recovery by activating the neuroendocrine stress response to surgery, caused by inflammation. Preemptive analgesia using flurbiprofen preoperatively is a potential treatment option to avoid hyperalgesia and prevent post-operative pain. However, the hydrophobicity and short in vivo elimination half-life of flurbiprofen are limitations. In this study, a strategy is presented for targeting inflammatory microenvironments using bioresponsive nanoparticles that simultaneously alleviate inflammation and inhibit hyperalgesia, effectively managing post-operative pain in rats. Our study demonstrates that flurbiprofen-conjugated hydroxyethyl starch can self-assemble into nanoparticles in water, imparting flurbiprofen with higher solubility in water and a longer half-life. Additionally, these biocompatible flurbiprofen-conjugated hydroxyethyl starch nanoparticles accumulate in the incision. Pathological analysis of nerves indicates that hyperalgesia was effectively inhibited by the preoperative administration of HES-Flurbiprofen nanoparticles in the rat incisional pain model. This hydroxyethyl starch-based nanoparticle system also suggests a promising and straightforward strategy for developing biocompatible and bioresponsive formulations for post-operative pain management.

Exosomal delivery of miR-200b-3p suppresses the growth of hepatocellular carcinoma cells by targeting ERG- and VEGF-mediated angiogenesis

Hepatocellular carcinoma (HCC) remains a lethal malignancy with limited treatment options. Recent discoveries have highlighted the pivotal role of miRNAs in HCC progression. We previously reported that the expression of miR-200b-3p was decreased in HCC cells and exosomal miR‐200b‐3p from hepatocytes inhibited angiogenesis by suppressing the expression of the endothelial transcription factor ERG (erythroblast transformation‐specific (ETS)‐related gene), leading to the hypothesis that the delivery of this miRNA may inhibit angiogenesis and suppress HCC growth in vivo. Here, we tested this hypothesis by using human HCC inoculation models. First, we transfected the human HepG2 HCC cells and established a stable cell line that overexpressed a high level of miR-200b-3p. When miR-200b-3p-overexpressing cells were injected into severe combined immunedeficiency (SCID)-beige mice, tumor growth was significantly reduced compared to tumors of control cells, with a reduction in the expression of ERG and vascular endothelial growth factor (VEGF) and subsequent angiogenesis. Intra-tumoral injection of exosomes containing high levels of miR-200b-3p also reduced the growth of parental HepG2 tumors with reduced ERG and VEGF expression and angiogenesis. These results validate the inhibitory role of miR-200b-3p in tumor angiogenesis, thereby suppressing HCC tumor growth, and provide a novel insight into its potential therapeutic application.

Current Knowledge and Perspectives of Immunotherapies for Neuroblastoma.

Neuroblastoma (NBL) cells highly express disialoganglioside GD2, which is restricted and weakly expressed in selected healthy cells, making it a desirable target of immunotherapy. Over the past two decades, application of dinutuximab, an anti-GD2 monoclonal antibody (mAb), has been one of the few new therapies to substantially improve outcomes to current levels. Given the persistent challenge of relapse and therapeutic resistance, there is an urgent need for new effective and tolerable treatment options for high-risk NBL. Recent breakthroughs in immune checkpoint inhibitor (ICI) therapeutics have not translated into high-risk NBL, like many other major pediatric solid tumors. Given the suppressed tumor microenvironment (TME), single ICIs like anti-CTLA4 and anti-PD1 have not demonstrated significant antitumor response rates. Meanwhile, emerging studies are reporting novel advancements in GD2-based therapies, targeted therapies, nanomedicines, and other immunotherapies such as adoptive transfer of natural killer (NK) cells and chimeric antigen receptors (CARs), and these hold interesting promise for the future of high-risk NBL patient care. Herein, we summarize the current state of the art in NBL therapeutic options and highlight the unique challenges posed by NBL that have limited the successful adoption of immune-modifying therapies. Through this review, we aim to direct the field's attention to opportunities that may benefit from a combination immunotherapy strategy.

UK survey of patient and caregiver perspectives on the impact of chronic kidney disease-associated anaemia

ObjectiveChronic kidney disease (CKD)-associated anaemia has substantial biopsychosocial impacts. This study explores the impact of CKD-associated anaemia and treatment preferences from the patient perspective.DesignCross-sectional survey.SettingAnonymised online survey implemented by Ipsos...

Combining Aloin with TIENAM ameliorates cecal ligation and puncture-induced sepsis in mice by attenuating inflammation and modulating abdominal cavity microbiota

Despite the high mortality rate, sepsis lacks specific and effective treatment options. Conventional antibiotics, such as TIENAM (TIE; imipenem and cilastatin sodium for injection), face challenges owing to the emergence of bacterial resistance, which reduces their effectiveness and causes adverse effects. Addressing resistance and judicious drug use is crucial. Our research revealed that aloin (Alo) significantly boosts survival rates and reduces inflammation and bacterial load in mice with sepsis, demonstrating strong antimicrobial activity. Using a synergistic Alo + TIE regimen in a cecal ligation and puncture (CLP)-induced sepsis model, we observed a remarkable increase in survival rates from 10 % to 75 % within 72 h compared with the CLP group alone. This combination therapy also modulated inflammatory markers interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α, mitigated tissue damage, regulated immune cells by lowering NK, activated CD8+ and CD4+ T cells while increasing peritoneal macrophages, and decreased the bacterial load in the peritoneal cavity. We noted a significant shift in the abdominal cavity microbiota composition post-treatment, with a decrease in harmful bacteria, such as Lachnospiraceae_NK4A136_group, Klebsiella, Bacillus, and Escherichia, and an increase in beneficial bacteria, such as Lactobacillus and Mucispirillum. Our study emphasizes the efficacy of combining Alo with TIE to combat sepsis, and paves the way for further investigations and potential clinical applications aiming to overcome the limitations of TIE and enhance the therapeutic prospects of Alo.

High-Resolution Magic Angle Spinning Nuclear Magnetic Resonance Spectroscopy of Paired Clinical Liver Tissue Samples from Hepatocellular Cancer and Surrounding Region.

The global burden of liver cancer is increasing. Timely diagnosis is important for optimising the limited available treatment options. Understanding the metabolic consequences of hepatocellular carcinoma (HCC) may lead to more effective treatment options. We aimed to document metabolite differences between HCC and matched surrounding tissues of varying aetiology, obtained at the time of liver resection, and to interpret metabolite changes with clinical findings. High-resolution magic angle spinning nuclear magnetic resonance (HRMAS-NMR) spectroscopy analyses of N = 10 paired HCC and surrounding non-tumour liver tissue samples were undertaken. There were marked HRMAS-NMR differences in lipid levels in HCC tissue compared to matched surrounding tissue and more subtle changes in low-molecular-weight metabolites, particularly when adjusting for patient-specific variability. Differences in lipid-CH3, lipid-CH2, formate, and acetate levels were of particular interest. The obvious differences in lipid content highlight the intricate interplay between metabolic adaptations and cancer cell survival in the complex microenvironment of liver cancer. Differences in formate and acetate might relate to bacterial metabolites. Therefore, documentation of metabolites in HCC tissue according to histology findings in patients is of interest for personalised medicine approaches and for tailoring targeted treatment strategies.

Treatment of Plantar Warts with a Nitric-Zinc Complex Solution: A Review of 72 Cases.

There are multiple conservative treatment options for plantar warts, but none have proven to be universally effective. Nitric acid is often used empirically by podiatrists in the treatment of plantar warts. A novel medical device or topical solution of nitric-zinc complex solution (NZCS) could potentially offer an effective and safe alternative for the targeted treatment of plantar warts. To observe the rate of complete healing of NZCS in a series of plantar wart cases and to establish the minimum number of product applications and time needed for healing. This will help standardize and protocolize its use. A descriptive study was conducted involving 72 patients who exhibited symptoms of plantar warts. These patients underwent chemical treatment using a nitric-zinc complex. The cure rate with NZCS was 59.2%. The average number of NZCS applications was 5.9 ± 3.0 and the mean duration of treatment was 9.4 ± 7.1 weeks. A recurrence rate of 6.7% was observed. The topical solution of the nitric-zinc complex is an effective treatment for plantar warts, which can be considered a first-line treatment option in the general population.

Nifedipine outperforms labetalol: A comparative analysis of hypertension management in black pregnancies

BackgroundNifedipine has previously exhibited superior efficacy to labetalol in managing hypertension in the non-pregnant Black population, establishing itself as a first-line treatment option. However, the unique challenges of hypertension during pregnancy, especially prevalent in Black individuals, remain underexplored in terms of effective medication choices. This gap highlights the need for targeted research on antihypertensive efficacy specifically within this population. ObjectiveThis study aims to evaluate the effectiveness of nifedipine versus labetalol in managing blood pressure in Black pregnancies. The primary measure is the mean systolic and diastolic blood pressure trajectories throughout pregnancy, determining the superiority of nifedipine in this context. Study designA retrospective cohort study was conducted at a multi-center institution in the metropolitan Detroit area, encompassing data from 1,235 Black pregnancies affected by chronic hypertension between 2015 and 2022. Mean blood pressure trajectories during pregnancy were fit by linear mixed effects model with a random intercept and time effect. ResultsPatients on nifedipine had an estimated 2.08 mmHg lower mean systolic and 1.60 mmHg lower mean diastolic blood pressure compared to those on labetalol, with significant p-values of 0.040 and 0.028. Additionally, nifedipine users were less likely to need increased doses, with an odds ratio of 0.28 (95 % CI: 0.19–0.40, p < 0.001) compared to labetalol users. ConclusionThis study provides compelling evidence that nifedipine outperforms labetalol in managing blood pressure during Black pregnancies. These findings suggest that the initiation of nifedipine should be considered in the management of chronic hypertension among Black pregnant individuals, offering a potentially more effective treatment option.

The Current Understanding of Molecular Mechanisms in Adenomyosis-Associated Infertility and the Treatment Strategy for Assisted Reproductive Technology.

Adenomyosis, endometriosis of the uterus, is associated with an increased likelihood of abnormal endometrial molecular expressions thought to impair implantation and early embryo development, resulting in disrupted fertility, including the local effects of sex steroid and pituitary hormones, immune responses, inflammatory factors, and neuroangiogenic mediators. In the recent literature, all of the proposed pathogenetic mechanisms of adenomyosis reduce endometrial receptivity and alter the adhesion molecule expression necessary for embryo implantation. The evidence so far has shown that adenomyosis causes lower pregnancy and live birth rates, higher miscarriage rates, as well as adverse obstetric and neonatal outcomes. Both pharmaceutical and surgical treatments for adenomyosis seem to have a positive impact on reproductive outcomes, leading to improved pregnancy and live birth rates. In addition, adenomyosis has negative impacts on reproductive outcomes in patients undergoing assisted reproductive technology. This association appears less significant after patients follow a long gonadotropin-releasing hormone agonist (GnRHa) protocol, which improves implantation rates. The pre-treatment of GnRHa can also be beneficial before engaging in natural conception attempts. This review aims to discover adenomyosis-associated infertility and to provide patient-specific treatment options.

Diagnostic challenges and burden of idiopathic hypersomnia: a systematic literature review.

Idiopathic hypersomnia (IH) is a rare neurological sleep disorder, characterized by excessive daytime sleepiness despite normal sleep duration, that can significantly impact patient's lives. The burden of IH goes beyond excessive daytime sleepiness, pervading all aspects of everyday life. Characteristic and burdensome symptoms of IH include sleep inertia/drunkenness, long sleep duration, and daytime cognitive dysfunction. This systematic review assessed current knowledge regarding IH diagnostic challenges and burden of illness. Literature searches for original epidemiological, clinical, humanistic, or economic research relevant to IH published between 2012 and 2022 in MEDLINE, Embase, Cochrane, gray literature (diagnostic criteria and treatment guidelines), conferences (2019-2022), and clinical trial databases yielded 97 articles. Findings indicate that IH remains a poorly defined diagnosis of exclusion that is difficult to distinguish from narcolepsy type 2 because of symptom overlap and inadequacies of objective testing. Consequently, individuals with IH endure diagnostic delays of up to 9 years. The economic burden of IH has not been characterized to any appreciable extent. Pharmacological treatment options can improve symptoms and functional status, but rarely restores normal levels of functioning. These findings highlight the need to reclassify central disorders of hypersomnolence. Further collaboration is now required between research groups to identify and validate objective markers to help redefine diagnostic criteria for IH. This would move IH into a position that could benefit from future targeted therapeutic interventions. The study was funded by Takeda Development Center Americas, Inc.

Approaches for Targeting Naegleria fowleri Using Nanoparticles and Artificial Peptides.

Naegleria fowleri is a free-living amoeba which causes primary amoebic meningoencephalitis (PAM). Although PAM is rare, the fatality rate is staggering at over 97%. So, the importance of finding an effective treatment and cure for PAM caused by N. fowleri is a crucial area of research. Existing research on developing novel therapeutic strategies to counter N. fowleri infection is limited. Since the blood-brain barrier (BBB) presents an obstacle to delivering drugs to the site of infection, it is important to employ strategies that can effectively direct the therapeutics to the brain. In this regard, our review focuses on understanding the physiology and mechanisms by which molecules pass through the BBB, the current treatment options available for PAM, and the recent research conducted in the decade of 2012 to 2022 on the use of nanomaterials to enhance drug delivery. In addition, we compile research findings from other central nervous system (CNS) diseases that use shuttle peptides which allow for transport of molecules through the BBB. The approach of utilizing BBB shuttles to administer drugs through the BBB may open up new areas of drug discovery research in the field of N. fowleri infection.

Adaptive evolution of carbapenem-resistant hypervirulent Klebsiella pneumoniae in the urinary tract of a single patient

The emergence of carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKp) is a growing concern due to its high mortality and limited treatment options. Although hypermucoviscosity is crucial for CR-hvKp infection, the role of changes in bacterial mucoviscosity in the host colonization and persistence of CR-hvKp is not clearly defined. Herein, we observed a phenotypic switch of CR-hvKp from a hypermucoviscous to a hypomucoviscous state in a patient with scrotal abscess and urinary tract infection (UTI). This switch was attributed to decreased expression of rmpADC, the regulator of mucoid phenotype, caused by deletion of the upstream insertion sequence ISKpn26. Postswitching, the hypomucoid variant showed a 9.0-fold decrease in mice sepsis mortality, a >170.0-fold reduction in the ability to evade macrophage phagocytosis in vitro, and an 11.2- to 40.9-fold drop in growth rate in normal mouse serum. Conversely, it exhibited an increased residence time in the mouse urinary tract (21 vs. 6 d), as well as a 216.4-fold boost in adhesion to bladder epithelial cells and a 48.7% enhancement in biofilm production. Notably, the CR-hvKp mucoid switch was reproduced in an antibiotic-free mouse UTI model. The in vivo generation of hypomucoid variants was primarily associated with defective or low expression of rmpADC or capsule synthesis gene wcaJ, mediated by ISKpn26 insertion/deletion or base-pair insertion. The spontaneous hypomucoid variants also outcompeted hypermucoid bacteria in the mouse urinary tract. Collectively, the ISKpn26-associated mucoid switch in CR-hvKp signifies the antibiotic-independent host adaptive evolution, providing insights into the role of mucoid switch in the persistence of CR-hvKp.