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Infection and Drug Resistance 2024Previous studies have indicated that the development of severe adverse events is associated with linezolid peak concentration (C), but the factors affecting linezolid C...
PURPOSE
Previous studies have indicated that the development of severe adverse events is associated with linezolid peak concentration (C), but the factors affecting linezolid C and evidences on therapeutic drug monitoring to anticipate toxicity in drug-resistant tuberculosis (DR-TB) patients have not been clarified clearly. This study aimed to explore the factors influencing linezolid C and investigate the association between linezolid concentration and hematological toxicity.
PATIENTS AND METHODS
This study included patients with drug-resistant tuberculosis treated with linezolid from January 2022 to September 2023. We analyzed the factors affecting linezolid C using chi-squared and binary logistic regression. The diagnostic utility of linezolid C in predicting hematological toxicity was evaluated using receiver operating characteristic (ROC) analysis.
RESULTS
A total of 76 patients were enrolled in the study. 63.20% met the standard rates for linezolid C. Age (P=0.036), weight (P=0.0016), and creatinine clearance (P=0.0223) significantly correlated with the C. Hematological toxicity was observed in 46.05% (35/76) of patients, characterized by thrombocytopenia (31.58%, 24/76), anemia (6.58%, 5/76), and leukopenia (21.05%, 16/76). ROC curve analysis confirmed the predictive value of linezolid C for thrombocytopenia with an area under curve of 0.728.
CONCLUSION
Suboptimal linezolid C was prevalent among patients with DR-TB, with age, weight, and renal function emerging as influential factors. Elevated linezolid C increases the risk of thrombocytopenia. Meticulous monitoring of linezolid C is imperative during anti-DR-TB therapy to tailor treatment and mitigate hematological toxicity.
PubMed: 38933777
DOI: 10.2147/IDR.S464429 -
Frontiers in Pharmacology 2024Unusual site deep vein thrombosis (DVT) was defined as venous thromboembolism (VTE) occurring outside the conventional deep veins of the lower extremity or pulmonary...
BACKGROUND
Unusual site deep vein thrombosis (DVT) was defined as venous thromboembolism (VTE) occurring outside the conventional deep veins of the lower extremity or pulmonary arteries. However, the optimal anticoagulation therapy for unusual site DVT remained unclear. This study aims to evaluate the efficacy and safety of rivaroxaban in unusual site DVT.
METHODS
This retrospective cohort study enrolled consecutive patients at Nanjing Drum Tower Hospital between January 2011 and December 2021 who were diagnosed with unusual site DVT. Patients were divided into two groups based on their ultimate medication choice: the warfarin group and the rivaroxaban group. The demographic characteristics were recorded for all enrolled patients. Clinical outcomes included recurrent VTE, bleeding complications and major bleeding.
RESULTS
A total of 1,088 patients were divided into warfarin ( = 514) and rivaroxaban ( = 574) groups. After the stabilized inverse probability of treatment weighting, Hazard Ratios for warfarin vs. rivaroxaban of recurrent VTE, bleeding complications and major bleeding were 0.52(95% CI: 0.25-1.08), 0.30(95% CI: 0.14-0.60), and 0.33 (95% CI, 0.13-0.74), respectively. Risk of clinical outcomes in specified subgroups for age, gender, renal function, thrombosis sites and diagnosis were assessed. The interaction of gender and treatment on major bleeding was significant (P for interaction = 0.062). Otherwise, there was no significant interaction between the other subgroups and the treatment group in terms of clinical outcomes.
CONCLUSION
Compared with warfarin, rivaroxaban exhibited comparable efficacy for the anticoagulant treatment of unusual site DVT, associated with a lower risk of bleeding complications and major bleeding.
PubMed: 38933677
DOI: 10.3389/fphar.2024.1419985 -
F1000Research 2023The risk of recurrence after nephrectomy for primary clear cell renal cell carcinoma (ccRCC) is estimated in daily practice solely based on clinical criteria. The aim of...
BACKGROUND
The risk of recurrence after nephrectomy for primary clear cell renal cell carcinoma (ccRCC) is estimated in daily practice solely based on clinical criteria. The aim of this study was to assess the prognostic relevance of common somatic mutations with respect to tumor aggressiveness and outcomes of ccRCC patients after definitive treatment.
METHODS
Primary tumors from 37 patients with ccRCC who underwent radical nephrectomy were analyzed for presence of somatic mutations using a 15-gene targeted next-generation sequencing (NGS) panel. Associations to histopathologic characteristics and outcomes were investigated in the study cohort (n=37) and validated in The Cancer Genome Atlas (TCGA) ccRCC cohort (n=451).
RESULTS
was the most frequently mutated gene (51%), followed by (27%), (13%), (13%), (5%), (5%), (5%), and (3%). One-third of patients did not have any somatic mutations within the 15-gene panel. The vast majority of tumors harboring no mutations at all or VHL-only mutations (51%) were more frequently of smaller size (pT1-2) and earlier stage (I/II), whereas presence of any other gene mutations in various combinations with or without was enriched in larger (pT3) and higher stage tumors (III) (p=0.02). No recurrences were noted in patients with unmutated tumors or -only mutations as opposed to three relapses in patients with non- somatic mutations (p=0.06). Presence of somatic mutations in , or genes in 451 TCGA ccRCC patients was associated with a significantly shorter disease-free survival (DFS) compared to those with unaltered tumors (q=0.01).
CONCLUSIONS
Preliminary findings from this ongoing study support the prognostic value of non- mutations including , and in primary ccRCC tumors as surrogates of earlier recurrence and potential selection for adjuvant immune checkpoint inhibition.
Topics: Humans; Carcinoma, Renal Cell; Male; Female; Kidney Neoplasms; Middle Aged; Mutation; Aged; Immune Checkpoint Inhibitors; Ubiquitin Thiolesterase; Neoplasm Recurrence, Local; Tumor Suppressor Proteins; Ataxia Telangiectasia Mutated Proteins; Von Hippel-Lindau Tumor Suppressor Protein; Prognosis; Histone-Lysine N-Methyltransferase; Adult; Transcription Factors; Aged, 80 and over; Nuclear Proteins; High-Throughput Nucleotide Sequencing; DNA-Binding Proteins; Histone Demethylases
PubMed: 38933491
DOI: 10.12688/f1000research.136087.2 -
Frontiers in Oncology 2024Renal cell carcinoma (RCC) is a common malignant kidney tumor; however, gastric metastasis is rare. We report the case of an 82-year-old male patient who developed...
Renal cell carcinoma (RCC) is a common malignant kidney tumor; however, gastric metastasis is rare. We report the case of an 82-year-old male patient who developed gastric metastasis 12 years after an initial diagnosis of RCC. The patient underwent endoscopic full-thickness resection (EFTR), and the gastric metastatic focus was successfully removed. Postoperative pathology and immunohistochemistry showed that the gastric metastasis originated from RCC. Although gastric metastasis of RCC is rare, it should be suspected in patients with a history of RCC or gastrointestinal symptoms. EFTR is associated with reduced trauma and greater retention of gastric tissue and function. It is a more appropriate choice than surgical resection; however, it requires more endoscopists.
PubMed: 38933445
DOI: 10.3389/fonc.2024.1394784 -
World Journal of Nuclear Medicine Jun 2024Technetium-99m ethylene dicysteine (Tc-99m EC) is a well-established, tubular tracer for diuretic renography. Few occasional cases have been reported in literature...
Technetium-99m ethylene dicysteine (Tc-99m EC) is a well-established, tubular tracer for diuretic renography. Few occasional cases have been reported in literature regarding visualization of liver, gallbladder (GB), or bowel due to increased hepatobiliary route of excretion of Tc-99m EC on diuretic renography. This study aimed to retrospectively review the incidence of visualization of liver, GB, or bowel and its clinical significance in Tc-99m EC diuretic renography. Data of all patients who underwent diuretic renography in the department from January 24, 2022 to March 31, 2023 was included in the study. The data was analyzed to assess the incidence of visualization of GB or bowel loops, correlation of the hepatobiliary localization with factors like age of the patient, concentration of 99m TcO4 solution, quality control parameters, presence of renal stone disease, serum creatinine, relative renal function, and effective renal plasma flow. Effect of hepatobiliary localization on scan interpretation and reporting was assessed. The retrospective analysis of 437 diuretic renograms revealed the hepatobiliary localization of tracer in 34 patients. Out of these 34 patients, 14 patients had only faint visualization of tracer at 4 hours delayed image. Twenty scans had visualization of both GB and bowel. Out of these 20 scans, GB and bowel were visualized during dynamic imaging in one scan, after initial 20 minutes in two scans and in 2 to 4 hours delayed images in rest of the 17 scans. Two out of 20 patients had increased serum creatinine, 16 patients had either single kidney or relative renal function less than 26%, and 12 patients had renal stone disease. Out of the four patients in whom relative renal function was more than 25%, one patient had raised serum creatinine and three patients had renal stone disease. Interpretation of images was affected only in three patients, in which reporting of the scans required single-photon emission computed tomography imaging and correlation with other imaging modalities. Hepatobiliary excretion of Tc-99m EC usually does not usually affect the scan interpretation and quantitative renogram analysis, but reader should be cognizant of the potential pitfalls during scan interpretation. In this study, we reviewed the possible causes of this hepatobiliary clearance and importance of additional views and correlation with other imaging modalities to clarify the suspicion arises for accurate reporting.
PubMed: 38933062
DOI: 10.1055/s-0044-1779748 -
Viruses May 2024(1) Background: Geriatric patients are at high risk of complications of Coronavirus disease-2019 (COVID-19) and are good candidates for antiviral drugs. (2) Methods: A...
(1) Background: Geriatric patients are at high risk of complications of Coronavirus disease-2019 (COVID-19) and are good candidates for antiviral drugs. (2) Methods: A retrospective study of electronic health records (EHRs) aiming to describe antiviral (nirmatrelvir and ritonavir (nirmatrelvir/r) or remdesivir) use, drug-drug interactions (DDIs) and adverse drug reactions (ADRs) in elderly patients (75 and over), hospitalized with mild-to-moderate COVID-19 between July 2022 and June 2023. (3) Results: Out of 491 patients (mean age: 86.9 years), 180 (36.7%) received nirmatrelvir/r, 78 (15.9%) received remdesivir, and 233 (47.4%) received no antiviral therapy. No association was found between the choice of antiviral and the demographic or medical data. No serious ADR was observed. Nirmatrelvir/r dosage adjustment was inadequate in 65% of patients with renal impairment. In total, 128 patients (71%) on nirmatrelvir/r had potential pharmacokinetic DDIs, with 43 resulting in a possibly related ADR. In the remdesivir group, pharmacodynamic DDIs were more frequent, with QTc prolongation risk in 56 patients (72%). Only 20 patients underwent follow-up ECG, revealing QTc prolongation in 4. (4) Conclusions: There is an underutilization of antivirals despite their justified indications. Nirmatrelvir/r dosage was rarely adjusted to renal function. Dose adjustments and closer monitoring are needed due to the high risk of drug interactions.
Topics: Humans; Antiviral Agents; Female; Male; Aged, 80 and over; Retrospective Studies; COVID-19 Drug Treatment; Alanine; Adenosine Monophosphate; SARS-CoV-2; Aged; Ritonavir; Drug Interactions; COVID-19; Adenosine
PubMed: 38932157
DOI: 10.3390/v16060864 -
Pharmaceutics May 2024Hydronephrosis resulting from unilateral ureteral obstruction (UUO) is a common cause of renal injury, often progressing to late-stage renal fibrosis or even potential...
Hydronephrosis resulting from unilateral ureteral obstruction (UUO) is a common cause of renal injury, often progressing to late-stage renal fibrosis or even potential renal failure. Renal injury and repair processes are accompanied by changes in cellular senescence phenotypes. However, the mechanism is poorly understood. The purpose of this study is to clarify the changes in senescence phenotype at different time points in renal disease caused by UUO and to further investigate whether eliminating senescent cells using the anti-senescence drug ABT263 could attenuate UUO-induced renal disease. Specifically, renal tissues were collected from established UUO rat models on days 1, 2, 7, and 14. The extent of renal tissue injury and fibrosis in rats was assessed using histological examination, serum creatinine, and blood urea nitrogen levels. The apoptotic and proliferative capacities of renal tissues and phenotypic changes in cellular senescence were evaluated. After the intervention of the anti-senescence drug ABT263, the cellular senescence as well as tissue damage changes were re-assessed. We found that before the drug intervention, the UUO rats showed significantly declined renal function, accompanied by renal tubular injury, increased inflammatory response, and oxidative stress, alongside aggravated cellular senescence. Meanwhile, after the treatment with ABT263, the rats had a significantly lower number of senescent cells, attenuated renal tubular injury and apoptosis, enhanced proliferation, reduced oxidative stress and inflammation, improved renal function, and markedly inhibited fibrosis. This suggests that the use of the anti-senescence drug ABT263 to eliminate senescent cells can effectively attenuate UUO-induced renal injury. This highlights the critical role of cellular senescence in the transformation of acute injury into chronic fibrosis.
PubMed: 38931822
DOI: 10.3390/pharmaceutics16060695 -
Nutrients Jun 2024Individuals with chronic kidney disease (CKD) often experience reduced muscle strength and diminished health-related quality of life (HRQoL), and engaging in regular...
BACKGROUND
Individuals with chronic kidney disease (CKD) often experience reduced muscle strength and diminished health-related quality of life (HRQoL), and engaging in regular exercise may improve them. The aim of this study was to assess the effect of intradialytic exercise using non-immersive virtual reality (VR) on body composition of patients with CKD on hemodialysis (HD).
METHODS
This was a substudy in a clinical trial of intradialytic exercise intervention using a non-immersive VR game in which the patient interacted by moving the lower limbs. Body composition was determined by BCM Fresenius multifrequency stereoscopic bioimpedance. Body mass index (BMI), fat tissue index (FTI), lean tissue index (LTI), extracellular/intracellular water (EIW), and phase angle (PA) were recorded in 52 patients, 24 in the control group (CG) and 28 in the exercise group (EG).
RESULTS
Statistically significant differences were observed between both groups. The LTI increased in the EG while it decreased in the CG. The FTI and the EIW decreased in the EG compared to the increase observed in the CG.
CONCLUSIONS
Intradialytic exercise using non-immersive VR was associated with an increase in LTI and a decrease in FTI of CKD patients on HD.
Topics: Humans; Body Composition; Renal Dialysis; Male; Renal Insufficiency, Chronic; Female; Middle Aged; Virtual Reality; Aged; Exercise Therapy; Body Mass Index; Quality of Life; Exercise; Adult; Electric Impedance
PubMed: 38931320
DOI: 10.3390/nu16121968 -
Nutrients Jun 2024Chronic kidney disease increases uremic toxins concentrations, which have been associated with intestinal dysbiosis. L. Moench has dietary fiber and bioactive... (Randomized Controlled Trial)
Randomized Controlled Trial
A Symbiotic Meal Containing Extruded Sorghum and Probiotic () Ameliorated Intestinal Health Markers in Individuals with Chronic Kidney Disease: A Secondary Analysis of a Subsample from a Previous Randomized and Controlled Clinical Trial.
BACKGROUND
Chronic kidney disease increases uremic toxins concentrations, which have been associated with intestinal dysbiosis. L. Moench has dietary fiber and bioactive compounds, while can promote beneficial health effects.
METHODS
It is a controlled, randomized, and single-blind clinical trial. Thirty-nine subjects were randomly separated into two groups: symbiotic group (SG), which received 100 mL of unfermented probiotic milk with strain and 40 g of extruded sorghum flakes; and the control group (CG), which received 100 mL of pasteurized milk and 40 g of extruded corn flakes for seven weeks.
RESULTS
The uremic toxins decreased, and gastrointestinal symptoms improved intragroup in the SG group. The acetic, propionic, and butyric acid production increased intragroup in the SG group. Regarding α-diversity, the Chao1 index was enhanced in the SG intragroup. The KEGG analysis revealed that symbiotic meal increased the intragroup energy and amino sugar metabolism, in addition to enabling essential amino acid production and metabolism, sucrose degradation, and the biosynthesis of ribonucleotide metabolic pathways.
CONCLUSIONS
The consumption of symbiotic meal reduced BMI, improved short-chain fatty acid (SCFA) synthesis and gastrointestinal symptoms, increased diversity according to the Chao1 index, and reduced uremic toxins in chronic kidney disease patients.
Topics: Humans; Renal Insufficiency, Chronic; Probiotics; Sorghum; Male; Female; Gastrointestinal Microbiome; Middle Aged; Single-Blind Method; Bifidobacterium longum; Fatty Acids, Volatile; Biomarkers; Aged; Dysbiosis; Adult; Intestines
PubMed: 38931207
DOI: 10.3390/nu16121852 -
Nutrients Jun 2024Zinc deficiency has been associated with the worsening of diabetes while zinc supplementation has been proposed to ameliorate diabetes. This study examined the effects...
Zinc deficiency has been associated with the worsening of diabetes while zinc supplementation has been proposed to ameliorate diabetes. This study examined the effects of marginal zinc deficiency (MZD) and zinc supplementation (ZS) on obesity, glycemic control, pancreatic islets, hepatic steatosis and renal function of Zucker diabetic fatty (ZDF) rats. Male ZDF rats were fed an MZD, zinc control (ZC) or ZS diet (4, 30 and 300 mg Zn/kg diet, respectively), and lean Zucker rats were fed a ZC diet for 8 weeks. MZD and ZS did not alter body weight or whole-body composition in ZDF rats. MZD ZDF rats had reduced zinc concentrations in the femur and pancreas, a greater number of enlarged pancreatic islets and a diminished response to an oral glucose load based on a 1.8-fold greater incremental area-under-the-curve (AUC) for glucose compared to ZC ZDF. ZS ZDF rats had elevated serum, femur and pancreatic zinc concentrations, unchanged pancreatic parameters and a 50% reduction in the AUC for insulin compared to ZC ZDF rats, suggesting greater insulin sensitivity. Dietary zinc intake did not alter hepatic steatosis, creatinine clearance, or levels of proteins that contribute to insulin signaling, inflammation or zinc transport in epididymal fat. Potential adverse effects of ZS were suggested by reduced hepatic copper concentrations and elevated serum urea compared to ZC ZDF rats. In summary, ZS improved the pancreatic insulin response but not the glucose handling. In contrast, reduced zinc status in ZDF rats led to impaired glucose tolerance and a compensatory increase in the number and size of pancreatic islets which could lead to β-cell exhaustion.
Topics: Animals; Rats, Zucker; Zinc; Dietary Supplements; Male; Insulin; Islets of Langerhans; Rats; Blood Glucose; Obesity; Insulin Resistance; Pancreas; Liver; Diabetes Mellitus, Experimental
PubMed: 38931174
DOI: 10.3390/nu16121819