Percutaneous Nephrostomy versus Ureteral Stent for Severe Urinary Tract Infection with Obstructive Urolithiasis: A Systematic Review and Meta-Analysis.

Background and Objectives: The European Association of Urology guidelines on urolithiasis highlight the limited evidence supporting the superiority of percutaneous nephrostomy (PCN) over retrograde ureteral stent placement for the primary treatment of infected hydronephrosis secondary to urolithiasis. We, therefore, conducted a systematic review and meta-analysis comparing the effects of PCN and retrograde ureteral stent in patients with severe urinary tract infections secondary to obstructive urolithiasis. Materials and Methods: Meta-analyses were performed to compare four outcomes: time for the temperature to return to normal; time for the white blood cell (WBC) count to return to normal; hospital length of stay; and procedure success rate. After a full-text review, eight studies were identified as relevant and included in our systematic review and meta-analysis. Results: No significant difference was detected between PCN and retrograde ureteral stenting for the time for the temperature to return to normal (p = 0.13; mean difference [MD] = -0.74; 95% confidence interval [CI] = -1.69, 0.21; I2 = 96%) or the time for the WBC count to return to normal (p = 0.24; MD = 0.46; 95% CI = -0.30, 1.21; I2 = 85%). There was also no significant difference between methods for hospital length of stay (p = 0.78; MD = 0.45; 95% CI = -2.78, 3.68; I2 = 96%) or procedure success rate (p = 0.76; odds ratio = 0.86; 95% CI = 0.34, 2.20; I2 = 47%). Conclusions: The clinical outcomes related to efficacy did not differ between PCN and retrograde ureteral stenting for severe urinary tract infection with obstructive urolithiasis. Thus, the choice between procedures depends mainly on the urologist's or patient's preferences.

Repeated Infusions of Bone-Marrow-Derived Mesenchymal Stem Cells over 8 Weeks for Steroid-Refractory Chronic Graft-versus-Host Disease: A Prospective, Phase I/II Clinical Study.

Chronic graft-versus-host disease (cGVHD) is a long-term complication of allogeneic hematopoietic stem cell transplantation associated with poor quality of life and increased morbidity and mortality. Currently, there are several approved treatments for patients who do not respond to steroids, such as ruxolitinib. Nevertheless, a significant proportion of patients fail second-line treatment, indicating the need for novel approaches. Mesenchymal stem cells (MSCs) have been considered a potential treatment approach for steroid-refractory cGVHD. To evaluate the safety and efficacy of repeated infusions of MSCs, we administered intravenous MSCs every two weeks to ten patients with severe steroid-refractory cGVHD in a prospective phase I clinical trial. Each patient received a total of four doses, with each dose containing 1 × 106 cells/kg body weight from the same donor and same passage. Patients were assessed for their response to treatment using the 2014 National Institutes of Health (NIH) response criteria during each visit. Ten patients with diverse organ involvement were enrolled, collectively undergoing 40 infusions as planned. Remarkably, the MSC infusions were well tolerated without severe adverse events. Eight weeks after the initial MSC infusion, all ten patients showed partial responses characterized by the amelioration of clinical symptoms and enhancement of their quality of life. The overall response rate was 60%, with a complete response rate of 20% and a partial response (PR) rate of 40% at the last follow-up. Overall survival was 80%, with a median follow-up of 381 days. Two patients died due to relapse of their primary disease. Immunological analyses revealed a reduction in inflammatory markers, including Suppression of Tumorigenicity 2 (ST2), C-X-C motif chemokine ligand (CXCL)10, and Secreted phosphoprotein 1(SPP1), following the MSC treatment. Repeated MSC infusions proved to be both feasible and safe, and they may be an effective salvage therapy in patients with steroid-refractory cGVHD. Further large-scale clinical studies with long-term follow-up are needed in the future to determine the role of MSCs in cGVHD.

Dysfunctional adipocytes promote tumor progression through YAP/TAZ-dependent cancer-associated adipocyte transformation.

Obesity has emerged as a prominent risk factor for the development of malignant tumors. However, the existing literature on the role of adipocytes in the tumor microenvironment (TME) to elucidate the correlation between obesity and cancer remains insufficient. Here, we aim to investigate the formation of cancer-associated adipocytes (CAAs) and their contribution to tumor growth using mouse models harboring dysfunctional adipocytes. Specifically, we employ adipocyte-specific BECN1 KO (BaKO) mice, which exhibit lipodystrophy due to dysfunctional adipocytes. Our results reveal the activation of YAP/TAZ signaling in both CAAs and BECN1-deficient adipocytes, inducing adipocyte dedifferentiation and formation of a malignant TME. The additional deletion of YAP/TAZ from BaKO mice significantly restores the lipodystrophy and inflammatory phenotypes, leading to tumor regression. Furthermore, mice fed a high-fat diet (HFD) exhibit decreased BECN1 and increased YAP/TAZ expression in their adipose tissues. Treatment with the YAP/TAZ inhibitor, verteporfin, suppresses tumor progression in BaKO and HFD-fed mice, highlighting its efficacy against mice with metabolic dysregulation. Overall, our findings provide insights into the key mediators of CAA and their significance in developing a TME, thereby suggesting a viable approach targeting adipocyte homeostasis to suppress cancer growth.

Fracture load of chairside CAD-CAM veneers fabricated with pre-and fully crystalized lithium disilicate ceramics.

PURPOSE: To evaluate the fracture load of chairside computer-aided design and computer-aided manufacturing (CAD-CAM) veneers fabricated with two conventional pre-crystallized and two fully crystallized lithium disilicate ceramic materials. MATERIALS AND METHODS: Seventy-five chairside CAD-CAM veneers (15 specimens/group) for maxillary right central incisors were fabricated with different lithium disilicate brands: (1) IPS e.max CAD; (2) Amber Mill; (3) Cerec Tessera; (4) n!ce Straumann; and (5) GC Initial LiSi Block. Restorations were cemented with resin luting cement (Variolink Esthetic, Ivoclar) to 3D-printed resin dies. Bonded restorations received 5000 thermal cycles and then were loaded until fracture. Statistical analysis included One-Way ANOVA. RESULTS: Conventional pre-crystallized e.max CAD displayed the highest fracture load value (640 N), followed by fully-crystallized n!ce Straumann (547 N), pre-crystallized Cerec Tessera (503 N), pre-crystallized Amber Mill (476 N), respectively; fully-crystallized GC Initial LiSi Block (431 N) displayed the lowest values. When comparing the fracture load of recent lithium disilicate ceramic material to the e.max group, which acted as the control, significant differences were noted. The LiSi Block GC group, in particular, had considerably higher mean difference values (208.867, p < 0.001, 95% CI [89.63, 328.10]), as did the Amber Mill group (164.200, p = 0.002, 95% CI [44.96, 283.44]) and CEREC Tessera group (137.533, p = 0.016, 95% CI [18.30, 256.77]). The e.max and n!ce Straumann groups had no statistically significant differences in mean scores (92.933, p = 0.198, 95% CI [-26.30, 212.17]). These findings imply that the clinical performance of recent lithium disilicate veneers varies when compared to the e.max CAD group. CONCLUSIONS: The fracture load of chairside CAD-CAM lithium disilicate veneers for maxillary central incisors varies according to the type of ceramic brands. Conventional pre-crystallized e.max CAD displayed higher fracture load than the recent pre- and fully-crystallized lithium disilicate materials, emphasizing the significance of choosing the right product based on the desired clinical outcome.

The IL-6 signaling pathway contributes critically to the immunomodulatory mechanism of human decidua-derived mesenchymal stromal cells.

Human bone marrow-derived mesenchymal stromal cells (BM-MSCs) have been proposed as a treatment for graft-versus-host disease (GVHD), which is a major complication following allogeneic hematopoietic cell transplantation. However, clinical trials have not yielded good results, and human decidua-derived mesenchymal stromal cells (DSCs) have been proposed as an alternative. In addition, the mechanism by which DSCs exert their immunomodulatory effects is still unknown. We found that knockdown of IL-6 in DSCs reduced the expression of PD-L1 and PD-L2, which are known as classical immune checkpoint inhibitors. Expression of PD-L1 and PD-L2 was restored by adding recombinant IL-6 to the DSCs. When DSCs and IL-6-knockdown DSCs were administered as treatment in a murine GVHD model, the group receiving IL-6-knockdown DSCs had significantly higher mortality and clinical scores compared to the group receiving DSCs. Taken together, these data suggest that the IL-6 signaling pathway is a crucial contributor to the immunosuppressive capacity of DSCs.

Sex, age, and species differences of perfluorooctanoic acid modeled by flow- versus permeability-limited physiologically-based pharmacokinetic models.

This study aimed to investigate sex, age, and species differences of perfluorooctanoic acid (PFOA) using physiologically-based pharmacokinetic (PBPK) models in rats and humans. PBPK models were generally developed as either flow- or permeability-limited models. The flow-limited model is cost-effective and allows for human PK prediction through simple allometric scaling, while the permeability-limited model can incorporate detailed information on the disposition process through in vitro-in vivo extrapolation (IVIVE). PFOA was administered via oral or intravenous administration with 5 mg/kg in male and female rats of different ages and the data was used to develop the PBPK models. Our results showed that both models successfully captured sex differences in rats, while only the flow-limited model with male rats and the permeability-limited model with both male and female rats provided comparable predictions in the human clinical study. More than the flow-limited model, the permeability-limited model effectively explained sex differences in rats and species differences through IVIVE. Additionally, the ontogeny-based mechanistic description of PFOA disposition enabled the interpretation of age- and sex-dependent pharmacokinetics. Although the flow-limited PBPK model lacked mechanistic interpretability compared to the permeability-limited model, it demonstrated reliable human prediction through simple allometric scaling. In conclusion, the permeability PBPK model could interpret age, sex, and species differences and it could improve the accuracy of human prediction.

TLR5 agonist in combination with anti-PD-1 treatment enhances anti-tumor effect through M1/M2 macrophage polarization shift and CD8+ T cell priming.

Immune checkpoint inhibitors have revolutionized anti-tumor therapy, notably improving treatment responses in various tumors. However, many patients remain non-responsive and do not experience benefits. Given that Toll-like receptors (TLRs) can counteract tumor immune tolerance by stimulating both innate and adaptive immune responses, TLR agonists are being explored as potential immune adjuvants for cancer treatment. In this study, we assessed the potential of enhancing the efficacy of immune checkpoint inhibitors by activating innate immunity with a TLR5 agonist. In a mouse tumor model, combination therapy with TLR5 agonist and anti-PD-1 significantly inhibited tumor growth. The TLR5 agonist shifted the balance from M2-like to M1-like macrophages and upregulated the expression of co-stimulatory molecules in macrophages. Furthermore, TLR5 agonist promoted the activation and tumor infiltration of CD8+ T cells. As a result, the TLR5 agonist augmented the anti-tumor efficacy of anti-PD-1, suggesting its potential in modulating the tumor microenvironment to enhance the anti-tumor response. Our findings point toward the possibility of optimizing immune checkpoint inhibitor therapy using TLR5 agonists.

Effectiveness of virtual reality interactive simulation practice in prosthodontic education: A systematic review and meta-analysis.

INTRODUCTION: Virtual reality-based interactive simulation (VRIS) provides a safe and controlled environment for dental students and professionals to develop skills and knowledge. This study aimed to investigate the effectiveness of using the VRIS for prosthodontic practice and to explore the trends, application areas, and users' attitudes towards VRIS. MATERIALS AND METHODS: This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for searching studies published until 21 March 2023 that reported quantitative or qualitative learning outcomes related to the use of VRIS for dental prosthodontic practice and clinical training. The quality of the included studies was assessed using the Medical Education Research Study Quality Instrument (MERSQI) and Newcastle-Ottawa Scale-Education (NOS-E) tools. A random-effects meta-analysis was conducted to compare the intervention group (utilizing VRIS) and the control group (employing conventional prosthodontic training methods) based on performance skill scores and task completion time, with a significance level set at <.05. RESULTS: The meta-analysis revealed that the utilization of VRIS generally improves students' performance scores (SMD = 1.04; 95% CI, -0.35 to 2.44; I2 > 50%; p = .13) and reduces task completion time (SMD = -0.03; 95% CI, 1.39-7.72; I2 > 50%; p = .93). Notably, using VRIS significantly enhanced the performance scores in implant surgery practice (SMD = 0.26; 95% CI, 0.09-0.42; p < .05). Additionally, the VRIS method significantly reduced task completion time in the cavity restorative preparation task (SMD = -1.19; 95% CI, -1.85 to -0.53; p < .05). CONCLUSION: Engaging in practice with VRIS has the potential to enhance learning proficiency in prosthodontic education. The advantages associated with VRIS encompass the provision of immediate feedback, decreased task completion time, heightened confidence and motivation, accelerated skill acquisition, improved performance scores, and increased learning engagement.

Automated scoring and augmented reality visualization software program for evaluating tooth preparations.

STATEMENT OF PROBLEM: Tooth preparation is an essential part of prosthetic dentistry; however, traditional evaluation methods involve subjective visual inspection that is prone to examiner variability. PURPOSE: The purpose of this study was to investigate a newly developed automated scoring and augmented reality (ASAR) visualization software program for evaluating tooth preparations. MATERIAL AND METHODS: A total of 122 tooth models (61 anterior and 61 posterior teeth) prepared by dental students were evaluated by using visual assessments that were conducted by students and an expert, and auto assessment that was performed with an ASAR software program by using a 3-dimensional (3D) point-cloud comparison method. The software program offered comprehensive functions, including generating detailed reports for individual test models, producing a simultaneous summary score report for all tested models, creating 3D color-coded deviation maps, and forming augmented reality quick-response (AR-QR) codes for online data storage with AR visualization. The reliability and efficiency of the evaluation methods were measured by comparing tooth preparation assessment scores and evaluation time. The data underwent statistical analysis using the Kruskal-Wallis test, followed by Mann-Whitney U tests for pairwise comparisons adjusted with the Benjamini-Hochberg method (α=.05). RESULTS: Significant differences were found across the evaluation methods and tooth types in terms of preparation scores and evaluation time (P<.001). A significant difference was observed between the auto- and student self-assessment methods (P<.001) in scoring both the anterior and posterior tooth preparations. However, no significant difference was found between the auto- and expert-assessment methods for the anterior (P=.085) or posterior (P=.14) tooth preparation scores. Notably, the auto-assessment method required significantly shorter time than the expert- and self-assessment methods (P<.001) for both tooth types. Additionally, significant differences in evaluation time between the anterior and posterior tooth were observed in both self- and expert-assessment methods (P<.001), whereas the evaluation times for both the tooth types with the auto-assessment method were statistically similar (P=.32). CONCLUSIONS: ASAR-based evaluation is comparable with expert-assessment while exhibiting significantly higher time efficiency. Moreover, AR-QR codes enhance learning and training experiences by facilitating online data storage and AR visualization.

Reduced toxicity (FluBu3) versus myeloablative (BuCy) conditioning in acute myeloid leukemia patients who received first allogeneic hematopoietic stem cell transplantation in measurable residual disease-negative CR1.

In the present study, reduced toxicity (FluBu3) and myeloablative (BuCy) conditioning were compared in patients with AML who received first allogeneic HSCT in MRD-negative CR1. The study included 124 adult patients who underwent HSCT from an HLA-matched (8/8) sibling, unrelated, or 1-locus mismatched (7/8) unrelated donor (MMUD). The median age was 45 years and intermediate cytogenetics comprised majority (71.8%). The 2-year OS, RFS, CIR and NRM for BuCy (n = 78, 62.9%) and FluBu3 (n = 46, 37.1%) groups were 78.3% and 84.5% (p = 0.358), 78.0% and 76.3% (p = 0.806), 7.7% and 21.5% (p = 0.074) and 14.3% and 2.2% (p = 0.032), respectively. At the time of data cut-off, relapse and NRM were the main causes of HSCT failure in each of the FluBu3 and BuCy arms. Among patients, 75% of relapsed FluBu3 patients had high-risk features of either poor cytogenetics or FLT3-ITD mutation compared with 16.7% of BuCy patients. The majority of NRM in the BuCy group was due to GVHD (73%), half of whom received MMUD transplantation. To conclude, the FluBu3 reduced toxicity conditioning showed comparable post-transplant OS and RFS to BuCy and was associated with significantly reduced NRM that was offset by a trend towards higher risk of relapse even in MRD-negative CR1 population.

A comparison study of pathological features and drug efficacy between Drosophila models of C9orf72 ALS/FTD.

Amyotrophic lateral sclerosis is a devastating neurodegenerative disease with a complex genetic basis, presenting both in familial and sporadic forms. The hexanucleotide (G4C2) repeat expansion in the C9orf72 gene, which triggers distinct pathogenic mechanisms, has been identified as a major contributor to familial and sporadic Amyotrophic lateral sclerosis cases. Animal models have proven pivotal in understanding these mechanisms; however, discrepancies between models due to variable transgene sequence, expression levels, and toxicity profiles complicate the translation of findings. Herein, we provide a systematic comparison of 7 publicly available Drosophila transgenes modeling the G4C2 expansion under uniform conditions, evaluating variations in their toxicity profiles. Further, we tested 3 previously characterized disease-modifying drugs in selected lines to uncover discrepancies among the tested strains. Our study not only deepens our understanding of the C9orf72 G4C2 mutations but also presents a framework for comparing constructs with minute structural differences. This work may be used to inform experimental designs to better model disease mechanisms and help guide the development of targeted interventions for neurodegenerative diseases, thus bridging the gap between model-based research and therapeutic application.

Impact of restoration thickness and tooth shade background on the translucency of zirconia laminate veneers: An in vitro comparative study.

Purpose: Our in vitro comparative study aimed to investigate the impact of thickness and tooth shade background on the translucency of highly translucent zirconia veneers. Materials and Methods: A total of 75 5Y-TZP zirconia veneers of shade A1 were fabricated with thicknesses of 0.50 mm (n = 25), 0.75 mm (n = 25), and 1.0 mm (n = 25). The translucencies were measured on composite resin teeth with shades A1, A2, A3, A3.5, and A4 using a digital color imaging spectrophotometer. Data were analyzed using ANOVA and post hoc Tukey's test (p < 0.05). Results: The translucency values were optimal for the veneers placed over the substrate teeth with shades A1 and A2, regardless of the veneer thickness. Additionally, veneers with a thickness of 0.50 mm exhibited significantly higher translucency than those with thicknesses of 0.75 mm and 1.0 mm. Conclusions: Our study demonstrated that the translucency of the highly translucent zirconia veneers was influenced by both veneer thickness and tooth shade background. The optimal veneer thickness for achieving the highest translucency was 0.50 for the veneers with A1 and A2 shades placed over the substrate teeth. Clinical Relevance: The optimal thickness for achieving the highest translucency of the highly translucent zirconia laminate veneers was 0.50 mm for the veneers with A1 and A2 shades placed over the substrate teeth. Clinicians and dental technicians could consider this when selecting materials for aesthetic restorations.

Immune profiling of patients with extranodal natural killer/T cell lymphoma treated with daratumumab.

Natural killer/T cell lymphoma (NKTCL) is a highly aggressive, heterogeneous non-Hodgkin lymphoma resulting from malignant proliferation of cytotoxic natural killer (NK) or T cells. Previous studies demonstrated variable expression of CD38 on NKTCL tumors. Daratumumab, a human IgGκ monoclonal antibody targeting CD38 with a direct on-tumor and immunomodulatory mechanism of action, was hypothesized to be a novel therapeutic option for patients with relapsed or refractory (R/R) NKTCL. In the phase 2 NKT2001 study (ClinicalTrials.gov Identifier: NCT02927925) assessing the safety and efficacy of daratumumab, a suboptimal overall response rate was seen in R/R NKTCL patients. One patient, whose tumors did not express CD38, responded to treatment, suggesting that the immunomodulatory activities of daratumumab may be sufficient to confer clinical benefit. To understand the suboptimal response rate and short duration of response, we investigated the immune profile of NKTCL patients from NKT2001 in the context of daratumumab anti-tumor activity. Tumor tissue and whole blood were, respectively, analyzed for CD38 expression and patient immune landscapes, which were assessed via cytometry by time-of-flight (CyTOF), multiparameter flow cytometry (MPFC), clonal sequencing, and plasma Epstein-Barr virus (EBV)-DNA level measurements. Changes observed in the immune profiles of NKTCL patients from NKT2001, including differences in B and T cell populations between responders and nonresponders, suggest that modulation of the immune environment is crucial for daratumumab anti-tumor activities in NKTCL. In conclusion, these findings highlight that the clinical benefit of daratumumab in NKTCL may be enriched by B/T cell-related biomarkers.

Antibiotic Sensitivity and Nasal Microbiome in Patients with Acute Bacterial Rhinosinusitis.

OBJECTIVES: Acute rhinosinusitis (ARS) is a common upper respiratory tract infection that is mostly of viral origin. However, little is known about the nasal microbiome profile at presentation and the changes caused by antibiotics in acute bacterial rhinosinusitis (ABRS). METHODS: This was a prospective single-center study. Overall, 43 ARS patients were screened and were assessed with the symptom questionnaires, nasal endoscopy, and Water's view. Five healthy subjects were recruited as controls. Middle meatal mucus samples were obtained using a cotton swab (for bacterial culture and antimicrobial susceptibility testing) and the suction technique (for 16S rRNA sequencing). After 1 week of antibiotic use (amoxicillin with clavulanic acid), we enrolled 13 patients with ABRS with positive isolates and middle meatal samples for 16S rRNA sequencing were obtained again. RESULTS: Overall, we demonstrated a significantly lower abundance of the Lactobacillaceae family in ABRS patients than in healthy controls. Resistant ABRS had different characteristics of middle meatal microbiomes when compared to sensitive ABRS as follows: (1) lower proportion of lactic acid bacteria, (2) increased pathogens such as Rhodococcus sp., Massila sp., Acinetobacter sp., and H. influenza, and (3) increased beta diversity. However, no remarkable changes were observed in the middle meatal microbiome after antibiotic use. CONCLUSION: We showed the roles of Lactobacillaceae in ABRS, and Acinetobacter and Massilia in case of amoxicillin resistance. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:1081-1088, 2024.

Longitudinal Changes in Quality of Life Before and After Thyroidectomy in Patients With Differentiated Thyroid Cancer.

OBJECTIVE: The objective of this prospective study was to assess longitudinal variations in health-related quality of life (HR-QOL) in patients diagnosed with differentiated thyroid cancer (DTC) before and after thyroidectomy. METHODS: A cohort of 185 DTC patients who underwent thyroidectomy between January 2013 and December 2017 and who completed all necessary questionnaires was evaluated. Their HR-QOL was gauged using the University of Washington Quality of Life questionnaire (UW-QOL) and the City of Hope Quality of Life-Thyroid Version questionnaire (QOL-TV) both prior to surgery and at 3 months, 6 months, 1 year, 2 years, 3 years, and 5 years postoperatively. RESULTS: Out of 185 patients, 150 (81.1%) were female, with an average age of 48.7 ± 12.9 years. For both UW-QOL and QOL-TV, the total composite QOL scores notably declined from preoperative levels to 3 months postoperatively, then gradually improved over 5 years, ultimately exceeding preoperative scores. Factors such as total thyroidectomy, radioactive iodine (RAI) ablation, and postoperative hypoparathyroidism were associated with lower physical composite QOL scores. Patients who underwent remote-access thyroidectomy expressed significantly higher satisfaction with appearance compared with those who had conventional thyroidectomy. Mood and anxiety were major clinical concerns both before and after surgery, showing considerable improvement postoperatively. CONCLUSION: For DTC patients, HR-QOL experienced a significant drop 3 months postsurgery, subsequently showing gradual improvement, surpassing preoperative QOL by 5 years. Factors contributing to improved physical QOL included the utilization of remote-access thyroidectomy, less extensive thyroidectomy, and the absence of RAI ablation and hypoparathyroidism.

Physiologically-based pharmacokinetic model for evaluating gender-specific exposures of N-nitrosodimethylamine (NDMA).

N-nitrosodimethylamine (NDMA) is classified as a human carcinogen and could be produced by both natural and industrial processes. Although its toxicity and histopathology have been well-studied in animal species, there is insufficient data on the blood and tissue exposures that can be correlated with the toxicity of NDMA. The purpose of this study was to evaluate gender-specific pharmacokinetics/toxicokinetics (PKs/TKs), tissue distribution, and excretion after the oral administration of three different doses of NDMA in rats using a physiologically-based pharmacokinetic (PBPK) model. The major target tissues for developing the PBPK model and evaluating dose metrics of NDMA included blood, gastrointestinal (GI) tract, liver, kidney, lung, heart, and brain. The predictive performance of the model was validated using sensitivity analysis, (average) fold error, and visual inspection of observations versus predictions. Then, a Monte Carlo simulation was performed to describe the magnitudes of inter-individual variability and uncertainty of the single model predictions. The developed PBPK model was applied for the exposure simulation of daily oral NDMA to estimate blood concentration ranges affecting health effects following acute-duration (≤ 14 days), intermediate-duration (15-364 days), and chronic-duration (≥ 365 days) intakes. The results of the study could be used as a scientific basis for interpreting the correlation between in vivo exposures and toxicological effects of NDMA.

Obstructive Uropathy Caused by Massive Fecal Impaction in a Patient With Congenital Anorectal Malformation and Neurogenic Bladder.

Anorectal malformations (ARMs) comprise a broad spectrum of congenital anomalies involving both anorectal and urogenital tracts. After diagnosis, urological problems should be evaluated in addition to surgical correction of ARMs. Commonly encountered urological problems in patients with ARMs are recurrent urinary tract infections, vesicoureteral reflux, and chronic kidney disease. Therefore, the proper timing of urination and appropriate defecation habits are essential for preserving renal function in patients with ARMs. Here, we report a case of acute hydronephrosis by severe stool impaction in a patient with a history of congenital ARMs and neurogenic bladder. In this case, the physicians should consider properly managing chronic constipation and urination in patients with ARMs despite successful surgical corrections.

Long-term Clinical Outcomes of Optimizing Combination Therapy for Primary Pulmonary Mucosa-associated Lymphoid Tissue Lymphoma: A Retrospective Study.

INTRODUCTION: Pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma progresses with advancing disease stage. However, no standard treatment approach has been established. This single-center retrospective study evaluated clinical and radiological characteristics, treatment modalities, and long-term prognosis of pulmonary MALT lymphoma. METHODS: The study included 42 patients diagnosed with pulmonary MALT lymphoma between October 2004 and July 2019. Primary therapeutic modalities were determined using modified Ann Arbor staging. Therapeutic response was evaluated via computed tomography and laboratory analyses every 6 months for 5 years. Radiological findings were categorized based on the Lugano classification as complete response (CR), partial response, stable disease (SD), or progressive disease. RESULTS: Initial treatment included observation (n=2), surgical resection (n=6), or systemic chemotherapy (n=34). Patients treated surgically had localized disease and achieved initial and long-term CR. Of the 34 patients who underwent chemotherapy, 30 achieved CR, 2 achieved SD, and 2 died. Overall and progression-free survival (PFS) rates were 93.9% and 54.3%, respectively. Multivariate analysis indicated that PFS was lower in patients with modified Ann Arbor stage III-IV lymphoma and those who did not achieve CR. CONCLUSIONS: Optimized treatment based on anatomical location, pulmonary function, and disease stage can improve long-term survival in patients with pulmonary MALT lymphoma.

Dynamic changes in physical function during intensive chemotherapy affect transplant outcomes in older adults with AML.

Introduction: Intensive chemotherapy (IC) can affect all geriatric assessment (GA) domains in older adults with acute myeloid leukemia (AML), but data on the effects of these changes on transplant outcomes are lacking. Methods: Therefore, we prospectively assessed the prognostic role of GA domains at diagnosis and allogeneic hematopoietic stem cell transplantation (allo-HSCT) in 51 patients with AML aged ≥60 years who achieved complete remission after IC. We performed both baseline and pre-allo-HSCT GA; moreover, physical function, including a short physical performance battery (SPPB), cognitive function, psychological function, nutritional status, and social support were examined. Results: All GA domains showed dynamic changes between the two time points. The directions of change were statistically significant for social support, self-reported physical and psychological functions, and distress, but not for nutritional status, cognitive function, or physical function. Among all GA domains at each time point, only poor physical function and its submaneuvers at diagnosis but not at allo-HSCT were significantly associated with inferior survival. In particular, since the direction of change varied between patients, we found that patients whose physical function improved before allo-HSCT were more likely to survive longer than those with persistently impaired SPPB (55.6% vs. 28.6%, p=0.268). Finally, persistent impairment in SPPB (28.6% vs. 65.9%, p=0.006), tandem stand (0% vs. 63.3%, p=0.012), sit-and-stand (41.2% vs. 70.6%, p=0.009), and gait speed (38.5% vs. 68.4%, p=0.027) further strongly predicted inferior survival. Discussion: This study showed that IC courses can induce dynamic changes in different directions in the GA domains of each patient and that changes in objectively measured physical function can predict transplant outcomes.