ABSTRACT
PURPOSE: Anthracycline-cyclophosphamide followed by docetaxel-containing chemotherapy is effective for perioperative breast cancer treatment. However, these treatments frequently induce oral mucositis (OM), with an incidence ranging from 20 to 50%. The association of OM development between different chemotherapeutic treatments remains unclear. Consequently, this study aimed to compare OM development during docetaxel-containing chemotherapy between patients with and without OM experience during previous anthracycline-cyclophosphamide treatments to assess the association between OM development and treatment regimens. METHODS: Seventy-two patients with breast cancer receiving anthracycline-cyclophosphamide followed by docetaxel-containing chemotherapy as a perioperative treatment were categorized into the control (no prior OM experience with anthracycline-cyclophosphamide) and OM-experience (OM development during previous treatment) groups and retrospectively evaluated. The primary endpoint was the incidence of all-grade OM in the first docetaxel-containing chemotherapy cycle. Additionally, the incidences of OM and dysgeusia during all treatment cycles and factors associated with the incidence of OM were evaluated. RESULTS: The incidence of all-grade OM in the first cycle was significantly higher in the OM-experience group (54.2%) than in the control group (10.4%; P < 0.0001). Furthermore, its incidence in all treatment cycles was higher in the OM-experience group (66.7%) than in the control group (12.5%, P < 0.0001). However, the incidence of dysgeusia did not differ between the groups. Multivariate logistic regression analysis revealed OM experience during previous anthracycline-cyclophosphamide treatment and concomitant pertuzumab use as independent risk factors for OM development in subsequent docetaxel-containing chemotherapy. CONCLUSION: Our study suggests that patients experiencing OM with anthracycline-cyclophosphamide during perioperative breast cancer treatment exhibit symptoms following subsequent docetaxel-containing chemotherapy.
Subject(s)
Anthracyclines , Antineoplastic Combined Chemotherapy Protocols , Breast Neoplasms , Cyclophosphamide , Docetaxel , Stomatitis , Humans , Breast Neoplasms/drug therapy , Breast Neoplasms/surgery , Female , Docetaxel/administration & dosage , Docetaxel/adverse effects , Cyclophosphamide/administration & dosage , Cyclophosphamide/adverse effects , Middle Aged , Stomatitis/chemically induced , Stomatitis/epidemiology , Retrospective Studies , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Anthracyclines/adverse effects , Anthracyclines/administration & dosage , Adult , Aged , Incidence , Taxoids/adverse effects , Taxoids/administration & dosage , Risk FactorsABSTRACT
Platelets have been reported to exert diverse actions besides hemostasis and thrombus formation in the body. However, whether platelets affect transporter activity remains to be determined. In this study, we examined the effects of platelets on the activity of amino acid transporter system A, which is known to be changed by various factors, and we clarified the mechanism by which platelets affect system A activity. Among system A subtypes, we found that sodium-coupled neutral amino acid transporter (SNAT) 4 played a central role in the transport activity of system A in HuH-7 human hepatoma cells. Interestingly, platelets showed a biphasic effect on system A activity: activated platelet supernatants (APS) including the granule contents released from platelets downregulated system A activity at lower concentrations and the downregulation was suppressed at higher concentrations. The downregulation was due to a decrease in the affinity of SNAT4 for its substrate and not a decrease in the SNAT4 abundance on the plasma membrane. In addition, APS did not decrease the expression level of SNAT4 mRNA. On the other hand, platelets did not affect system A activity when the platelet suspension was added to HuH-7 cells. These results indicate that platelets indirectly affect the transport activity of system A by releasing bioactive substances but do not directly affect it by binding to HuH-7 cells.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Amino Acid Transport Systems/metabolism , Blood Platelets/metabolism , Cell Membrane/metabolism , RNA, Messenger/geneticsABSTRACT
Although carboplatin (CBDCA) is classified as a moderately emetogenic agent, the majority of guidelines recommend the use of a neurokinin-1 receptor antagonist in addition to a 5-hydroxytryptamine type 3 receptor antagonist with dexamethasone (DEX) for CBDCA-containing chemotherapy because of its higher emetogenic risk. However, the additional efficacy of aprepitant (APR) in CBDCA-containing treatment remains controversial, and data on multiple-day treatments are limited. Etoposide (ETP) was administered on days 1-3 in the CBDCA + ETP regimen, and it is important to evaluate suitable antiemetic therapy for the regimen. Therefore, we evaluated the efficacy of additional APR in CBDCA + ETP. Patients were divided into two groups and retrospectively evaluated. One was the control group, which was prophylactically administered palonosetron (PALO) and DEX, and the other was the APR group, which received APR orally with PALO and DEX. The primary endpoint was complete response (CR) between the groups. The overall CR rates were 75.0 and 76.4% in the control and APR groups, respectively, with no significant difference (p = 1.00). In the acute phase, it was 88.9 and 97.2%, respectively, and 86.1 and 79.2% in the delayed phase, respectively, without significant differences (p = 0.10 and 0.38, respectively). The incidence and severity of nausea, vomiting, and anorexia were not significantly different between the two groups in the acute and delayed phases. Our findings suggest that combining APR with PALO and DEX does not improve the CR rate in CBDCA + ETP therapy.
Subject(s)
Antiemetics , Aprepitant , Carboplatin , Dexamethasone , Etoposide , Nausea , Palonosetron , Vomiting , Aprepitant/therapeutic use , Aprepitant/administration & dosage , Carboplatin/administration & dosage , Carboplatin/therapeutic use , Carboplatin/adverse effects , Humans , Dexamethasone/administration & dosage , Dexamethasone/therapeutic use , Palonosetron/administration & dosage , Palonosetron/therapeutic use , Male , Etoposide/administration & dosage , Etoposide/therapeutic use , Antiemetics/administration & dosage , Antiemetics/therapeutic use , Female , Middle Aged , Vomiting/chemically induced , Vomiting/prevention & control , Aged , Nausea/chemically induced , Nausea/prevention & control , Retrospective Studies , Adult , Drug Therapy, Combination , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Quinuclidines/administration & dosage , Quinuclidines/therapeutic use , Morpholines/administration & dosage , Morpholines/therapeutic use , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/adverse effects , Isoquinolines/administration & dosage , Isoquinolines/therapeutic use , Treatment OutcomeABSTRACT
OBJECTIVE: Irinotecan (IRI) is an anticancer drug that is frequently used to treat colorectal, gastric, and pancreatic cancers. Its side effects include cholinergic symptoms, such as diarrhea, abdominal pain, nausea, and hyperhidrosis. Anticholinergic medicines are frequently used for treatment or prophylaxis; however, the risk factors for the failure of a single prophylactic anticholinergic administration remain unclear. Moreover, an appropriate anticholinergic drug for prophylaxis remains unknown. Thus, we aimed to identify the risk factors associated with the failure of a single prophylactic dose of anticholinergic drugs for IRI-induced cholinergic symptoms and to evaluate the usefulness of multiple prophylactic doses of anticholinergic drugs. MATERIALS AND METHODS: Patients who underwent IRI treatment for colorectal, gastric, or pancreatic cancer and received prophylactic anticholinergic drugs for IRI-induced cholinergic symptoms (n = 135) were retrospectively evaluated. Univariate and multivariate logistic regression analyses were performed to identify the risk factors for failure of a single prophylactic dose of anticholinergic drugs. We also evaluated the efficacy of multiple prophylactic anticholinergic drug administration. RESULTS: Based on univariate and multivariate analyses, colorectal cancer, female sex, and prophylactic use of scopolamine butyl bromide were identified as risk factors for failure of a single prophylactic dose of anticholinergic drugs. The efficacy of multiple prophylactic doses was confirmed to be 95% of the patients who had a single prophylactic failure due to temporary effect but symptom appearance after a certain period of time (wearing-off). CONCLUSION: We determined that colorectal cancer, female sex, and prophylactic use of scopolamine butyl bromide were risk factors associated with the failure of a single prophylactic dose of anticholinergic drugs, and that multiple prophylactic doses for wearing-off can be a promising method.
Subject(s)
Cholinergic Antagonists , Colorectal Neoplasms , Hydrocarbons, Brominated , Humans , Female , Irinotecan/adverse effects , Retrospective Studies , Cholinergic Antagonists/adverse effects , Risk Factors , Cholinergic Agents , Butylscopolammonium Bromide , Colorectal Neoplasms/drug therapyABSTRACT
Conventional coronal CT scans of paranasal sinuses, aligned perpendicularly to the nasal floor, often deviate significantly from the endoscopic view during sinus surgery. This discrepancy complicates the interpretation of anatomical structures. In response, we propose the utilization of anteriorly tilted coronal CT slices to enhance anatomical understanding. These slices align more closely with the endoscopic view, fostering an intuitive grasp of paranasal sinus anatomy. This study aims to quantify the tilt of the endoscope to the nasal floor during endoscopic sinus surgery. To figure out the tilt of the endoscopically true coronal slices, we calculated the tilt of the endoscope to the nasal floor in the operative setting by taking pictures of the operation and measuring the image and sagittal CT. Fourteen patients (25 sides of paranasal sinuses) were analyzed. Endoscope tilts to the nasal floor were measured at different anatomical landmarks: 16.2 ± 9.7 degrees (lower edge of ground lamella), 29.8 ± 7.9 degrees (central ground lamella), 62.3 ± 10.1 degrees (most superior part), and 25.6 ± 7.0 degrees (optic canal). In conclusion, we showed the actual tilt of the endoscope to the nasal floor during endoscopic sinus surgery. A 30-degree anteriorly tilted coronal scan for frontal recess and sphenoid sinus is more intuitive than a traditional coronal scan, which helps surgeons understand the complex sinus anatomy.
Subject(s)
Endoscopy , Paranasal Sinuses , Tomography, X-Ray Computed , Humans , Paranasal Sinuses/surgery , Paranasal Sinuses/diagnostic imaging , Paranasal Sinuses/anatomy & histology , Tomography, X-Ray Computed/methods , Endoscopy/methods , Male , Female , Middle Aged , Adult , AgedABSTRACT
PURPOSE: Endoscopic nasal and sinus surgery is a surgical procedure frequently performed by otolaryngologists. Postoperative bleeding is detrimental to both healthcare providers and patients. We investigated the epidemiology of postoperative bleeding during endoscopic nasal and sinus surgery and explored possible bleeding triggers. METHODS: We evaluated the patients who underwent endoscopic nasal and sinus surgery. Data regarding the age, sex, presence of hypertension, and abnormal coagulability, including oral anticoagulants, diagnoses, operative procedures, intraoperative use of drills and blood loss, and postoperative antimicrobial administration of eligible patients, were extracted from medical records and retrospectively reviewed. RESULTS: One hundred and eighty-six patients underwent endoscopic nasal or sinus surgery during the study period, and postoperative bleeding occurred in 9 patients (4.8%). Posterior nasal neurotomy (PNN) was the procedure most likely to cause postoperative bleeding (4 surgeries, 13.3%). Postoperative antimicrobial administration significantly reduced the incidence of postoperative bleeding (p = 0.04). CONCLUSIONS: Postoperative bleeding requiring intervention occurs in 4.8% of cases, and PNN is associated with a high risk of postoperative bleeding. Wound infection is a potential cause of postoperative bleeding, and antimicrobial administration should be considered in addition to local treatment.
Subject(s)
Anti-Infective Agents , Endoscopy , Humans , Retrospective Studies , Endoscopy/adverse effects , Postoperative Hemorrhage/epidemiology , Postoperative Hemorrhage/etiology , NoseABSTRACT
PURPOSE: In Japan, two types of tests for diagnosing olfactory disorders, T and T (T&T) olfactometry and intravenous olfactory tests, are covered by insurance and performed on patients with olfactory disorders. This study examined the validity of these olfactory tests and whether psychophysical or morphological tests are more helpful in evaluating olfactory disorders. METHODS: We evaluated patients who visited our department and underwent two types of olfaction tests and sinus computed tomography (CT). Data regarding the age, sex, peripheral blood eosinophil percentage, presence of bronchial asthma, diagnoses, olfactory symptom score, results of the two olfactory tests, and CT findings in eligible patients were extracted from medical records and retrospectively reviewed. RESULTS: One hundred and sixty-three patients underwent all tests during the study period. The results of the T&T olfactometry and intravenous olfactory tests were significantly correlated. However, only the results of T&T olfactometry and olfactory cleft opacification on CT were statistically significant predictors of the olfactory symptom scores. CONCLUSION: T&T olfactometry and CT evaluations of olfactory cleft opacification helped evaluate olfactory dysfunction. It is important to note that intravenous olfactory tests are best performed with careful control and not blindly to assess olfactory disorders.
ABSTRACT
Inflammatory bowel disease (IBD) is characterized by chronic intestinal inflammation and its treatment varies widely; however, when inflammation is high, a complete nutrient containing pre-digested elemental diet (ED) is used to preserve the intestinal tract. In this study, we investigated the mechanisms underlying the effectiveness of EDs for IBD using mice. C57BL/6 mice were orally treated with the ED (5 mL/day) and its ingredient L-tryptophan (Trp) (1-100 mg/kg), respectively. Flow cytometry analysis revealed that treatment with the ED and Trp (10 and 100 mg/kg) significantly increased the percentage of splenic CD4+-/CD25+-/Foxp3+ regulatory T cells (Tregs). In the 2% DSS-induced colitis-mouse model, Trp administration (100 mg/kg) led to a significant decrease in TNF-α and increase in IL-10 in the serum as well as a significant decrease in the inflammation score. Furthermore, the aryl hydrocarbon receptor (AhR) agonistic activity, which is a key function of Treg induction, of Trp and 15 Trp metabolites was characterized using a highly sensitive DR-EcoScreen cell assay. Five Trp metabolites, including L-kynurenine, acted as AhR agonists, while Trp did not. Taken together, these results suggest that the ED treatment has a Trp-dependent immunoregulatory effect, and several Trp metabolites that activate the AhR might contribute to induction of remission in patients with IBD.
Subject(s)
Inflammatory Bowel Diseases , Tryptophan , Humans , Animals , Mice , Tryptophan/pharmacology , Tryptophan/metabolism , Receptors, Aryl Hydrocarbon/metabolism , Mice, Inbred C57BL , Inflammatory Bowel Diseases/drug therapy , InflammationABSTRACT
PURPOSE: Thrombocytopenia is a major event associated with linezolid (LZD) therapy. Factors affecting LZD-induced thrombocytopenia (LIT) have been reported in previous studies. However, several issues pertaining to LIT have not yet been clarified. In the present study, we used Japanese big data to investigate associated factors and their high-risk combinations that influence LIT. METHODS: Patients administered LZD between May 2006 and October 2020 were included in this study. LIT was defined as either a 30% or more reduction from the baseline platelets or platelet values of < 100,000/µL. We evaluated factors affecting LIT and combinations of factors that alter LIT risk according to a decision tree (DT) analysis, a typical machine learning method. RESULTS: We successfully enrolled 1399 patients and LIT occurred in 44.7% of the patients (n = 626). We classified the laboratory data on renal function, LZD duration, age, and body weight (BW) into smaller categories. The results of multivariate analysis showed that prolonged LZD therapy, BW < 45 kg, estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2, and dialysis were risk factors for LIT. The DT analysis revealed that the highest risk was a combination of LZD duration ≥ 14 days and eGFR < 30 mL/min/1.73 m2. CONCLUSIONS: The present study extracted four risk factors and identified high-risk combinations for LIT. Patients with these risk factors should be closely monitored.
Subject(s)
Anemia , Thrombocytopenia , Humans , Linezolid/adverse effects , Electronic Health Records , Big Data , East Asian People , Thrombocytopenia/chemically induced , Anemia/chemically induced , Risk Factors , Anti-Bacterial AgentsABSTRACT
PURPOSE: Chemotherapy-induced nausea and vomiting (CINV) are common adverse events in patients undergoing emetogenic chemotherapy. Palonosetron, a second-generation 5-hydroxytryptamine-3 receptor antagonist (5-HT3 RA), has demonstrated non-inferiority to first-generation 5-HT3 RAs for CINV in pediatric patients. Although palonosetron has a long half-life and prolonged antiemetic action, its efficacy against delayed CINV in pediatric patients is not well understood. Therefore, this meta-analysis of randomized controlled trials (RCTs) aimed to evaluate the efficacy of palonosetron for delayed CINV in pediatric patients. METHODS: A literature search of MEDLINE/PubMed, Embase, Cochrane Library, and Web of Science databases was performed. A meta-analysis was performed using forest plots, and risk ratios (RRs) and 95% confidence intervals (CIs) were calculated. A funnel plot was constructed to explore publication bias. RESULTS: The literature search retrieved 842 records, of which 23 full-text articles were assessed, including six RCTs. Meta-analysis of four RCTs that reported on the complete response (CR: defined as no emesis and no rescue medication) rate for delayed CINV revealed that palonosetron was statistically superior to first-generation 5-HT3 RAs (RR = 1.21 [95% CI 1.09-1.35]; p < 0.01). Although the number of studies included was small, no publication bias was observed in the funnel plots. In addition, the CR rate for overall and acute CINV was also significantly higher for palonosetron (RR = 1.25 [95% CI 1.01-1.54]; p = 0.04 and RR = 1.06 [95% CI 1.01-1.12]; p = 0.03, respectively). CONCLUSION: Palonosetron is effective in the prophylaxis of delayed CINV in pediatric patients.
Subject(s)
Antiemetics , Antineoplastic Agents , Humans , Child , Palonosetron/therapeutic use , Isoquinolines/therapeutic use , Quinuclidines/therapeutic use , Nausea/chemically induced , Nausea/prevention & control , Nausea/drug therapy , Antiemetics/therapeutic use , Vomiting/chemically induced , Vomiting/prevention & control , Vomiting/drug therapy , Antineoplastic Agents/adverse effects , Serotonin 5-HT3 Receptor Antagonists/therapeutic useABSTRACT
PURPOSE: Anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibodies are effective in treating RAS wild-type metastatic colorectal cancer (mCRC). However, their administration induces skin toxicity, markedly reducing patients' quality of life. This study is aimed at identifying the risk factors associated with anti-EGFR monoclonal antibody-induced skin toxicities. METHODS: Patients with mCRC (n = 116) who received anti-EGFR monoclonal antibody treatment were retrospectively evaluated. Primary endpoint was evaluation of the risk factors for grade ≥ 2 overall skin toxicities during all the treatment periods. Furthermore, factors associated with each grade ≥ 2 skin symptoms were assessed. RESULTS: Incidence of total grade ≥ 2 skin toxicity symptoms was 61.2%, and those of grade ≥ 2 rash, dry skin, fissures, and paronychia were 34.5%, 25.9%, 20.7%, and 25.0%, respectively. Multivariate logistic regression analyses revealed that liver metastasis was an independent risk factor for overall grade ≥ 2 skin toxicities (adjusted odds ratio [OR], 2.88; 95% confidence interval [CI], 1.22-6.78; P = 0.02) and prophylactic administration of antibiotics as a preventive factor (OR 0.10; 95%CI 0.01-0.91; P = 0.04). For grade ≥ 2 rash, prophylactic use of systemic antibiotics and topical steroid ointment was a preventive factor (OR 0.37; 95%CI 0.16-0.89; P = 0.03). Moreover, liver metastasis (OR 8.37; 95%CI 1.98-35.47; P = 0.004) and prophylactic administration of antibiotics (OR 0.15; 95%CI 0.03-0.76; P = 0.02) were significantly associated with grade ≥ 2 paronychia. CONCLUSION: Liver metastasis was suggested to be a risk factor for the incidence of overall grade ≥ 2 skin toxicities; moreover, preemptive systemic antibiotic administration drastically decreased this risk during all periods of anti-EGFR treatment for mCRC.
Subject(s)
Antineoplastic Agents , Colonic Neoplasms , Colorectal Neoplasms , Exanthema , Paronychia , Rectal Neoplasms , Humans , Panitumumab/adverse effects , Cetuximab/adverse effects , Paronychia/chemically induced , Quality of Life , Retrospective Studies , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/pathology , ErbB Receptors/metabolism , Antibodies, Monoclonal/adverse effects , Antineoplastic Agents/adverse effects , Exanthema/chemically induced , Anti-Bacterial Agents/therapeutic use , Risk FactorsABSTRACT
BACKGROUND: Anti-epidermal growth factor receptor (EGFR) antibodies often cause skin toxicities. Preemptive skin treatments using systemic antibiotics with or without topical steroid are reportedly effective although the most suitable method remains unclear. This study aimed to determine whether combination prophylaxis using systemic minocycline and topical steroid is superior to minocycline alone in a real-world metastatic colorectal cancer (mCRC) treatment. METHODS: Patients with mCRC (n = 87) who received anti-EGFR monoclonal antibodies were retrospectively assessed. The primary objective was to compare the incidence of grade ≥ 2 overall skin toxicities during all treatment periods between the control group receiving prophylactic minocycline 100 mg/day, and the combination prophylaxis group receiving minocycline 100 mg/day + topical steroid. The incidence of each skin symptom was also evaluated. RESULTS: The incidence of grade ≥ 2 overall skin toxicities was 63.6% in the control and 56.9% in the combination groups, with no significant difference (P = 0.63). Similarly, the incidence of grade ≥ 2 dry skin, fissures, paronychia, and pruritus did not significantly differ. In addition, incidence of all-grade skin toxicities was not different. However, the incidence of grade ≥ 2 papulopustular rashes was significantly lower in the combination group (23.1% vs. 50.0%, P = 0.03). Propensity score-matched analysis supported these results. Multivariate logistic regression analysis showed no significant association between combination prophylaxis and grade ≥ 2 overall skin toxicities, but it did show a reduction in grade ≥ 2 papulopustular rashes. CONCLUSION: Adding topical steroids to systemic minocycline did not mitigate grade ≥ 2 overall skin toxicities induced by anti-EGFR antibodies; however, it significantly improved papulopustular rashes.
Subject(s)
Colonic Neoplasms , Exanthema , Skin Diseases , Humans , Minocycline/adverse effects , Ointments , Retrospective Studies , Steroids , Intercellular Signaling Peptides and ProteinsABSTRACT
PURPOSE: Taxane-associated acute pain syndrome (T-APS) is one of the most bothersome adverse effects caused by taxanes. We have previously reported the attenuating effect of dexamethasone (DEX) on T-APS and its risk factors under DEX prophylaxis. However, the appropriate DEX dosage administration remains unclear. Therefore, this study aimed to investigate whether DEX dose-dependently prevents T-APS in breast cancer patients. METHODS: We retrospectively evaluated patients with breast cancer who received docetaxel (75 mg/m2)-containing chemotherapy without pegfilgrastim and regular non-steroidal anti-inflammatory drugs. The patients were divided into 4 mg/day and 8 mg/day DEX groups, with each DEX dosage on days 2-4 (n = 68 for each group). Primary endpoint was the comparison of all-grade T-APS incidence between the groups. Propensity score-matching was performed to adjust the baseline factors between the groups, and outcomes in the matched-population were also assessed. RESULTS: The incidence of all-grade T-APS was 72.1% in 4 mg/day group and 48.5% in 8 mg/day group, which was significantly lowered by higher DEX dosage (P = 0.008). The severity of T-APS was also significantly reduced in 8 mg/day group (P = 0.02). These results were confirmed in the propensity score matching. Multivariate logistic analysis showed that higher DEX dosage was an independent T-APS preventive factor, whereas age < 55 years was a risk factor. Moreover, DEX-dosage-associated adverse effects similarly appeared in both groups. CONCLUSION: Our study suggested that DEX dose-dependently prevents T-APS in breast cancer treatment. As understanding of the nature of T-APS and its appropriate management can significantly contribute to less onerous chemotherapy provision, further studies are required.
Subject(s)
Acute Pain , Breast Neoplasms , Humans , Middle Aged , Female , Breast Neoplasms/drug therapy , Acute Pain/chemically induced , Retrospective Studies , Taxoids , Dexamethasone/therapeutic useABSTRACT
The Child-Pugh score is widely used to assess liver function and estimate drug clearance in patients with liver cirrhosis. Recently, the albumin-bilirubin (ALBI) score, which objectively assesses liver function based only on albumin and total bilirubin levels, was developed as a new method. The purpose of this study was to analyze the relationship between the liver function assessment method and the plasma concentration of voriconazole (VRCZ), an antifungal drug for patients with liver cirrhosis. This single-center retrospective study enrolled 159 patients who received VRCZ between 2012 and 2020. In patients administered VRCZ orally, the median concentration to dose (C : D) ratio increased with the progression of Child-Pugh and ALBI grades. Positive correlations between the ALBI score and VRCZ C : D ratio were observed in patients with cirrhosis (r = 0.52 (95% confidence interval, 0.069-0.79); p < 0.05). In addition, a highly negative correlation was observed between the ALBI score and VRCZ daily maintenance dose (r=-0.79 (95% confidence interval, -0.92 to -0.50); p < 0.0001). In contrast, for patients administered VRCZ intravenously, no increase in C : D ratio was observed for both Child-Pugh and ALBI scores compared to the non-liver cirrhosis group. This may be because the injection is often used in severely ill patients, and factors other than impaired liver function may affect the plasma concentrations of VRCZ. In conclusion, the ALBI score was shown to be useful in predicting VRCZ clearance as well as the Child-Pugh score, and the initial dose of VRCZ might be determined according to the ALBI score.
Subject(s)
Bilirubin , Liver Neoplasms , Humans , Voriconazole , Serum Albumin/analysis , Retrospective Studies , Liver Cirrhosis/drug therapy , PrognosisABSTRACT
The modified Cockcroft-Gault (CG) equation, previously developed for an aged-oriented cohort, was validated in a newly obtained dataset. Estimates of creatinine clearance (CCr) using this equation were found to be more accurate than those determined using the conventional CG equation, particularly for patients exceeding 65 years of age. We identified a subset of patients in this cohort whose estimates were inadequate. Using statistical analysis, we found that the deviation from estimates was attributed to a decreased albumin level. In addition, we determined a reduced albumin cutoff value for the modified CG equation to obtain a good estimate. Univariate linear regression analysis was applied to measure the CCr in this cohort and identify parameters related to body composition, and we found that extracellular water (ECW)/total body water (TBW) and body fat (%) were relevant. Using measured values of ECW/TBW and body fat (%), a multivariate linear regression (MLR) estimating equation was developed based on the modified CG equation. This equation was applied to a cohort over 65 years of age, and it was found that a good estimate was obtained for older patients with low albumin levels. Thus, we propose a flow diagram that illustrates conditions for selecting an appropriate estimating equation from among the CG, modified CG, and MLR equations.
Subject(s)
Body Composition , Kidney , Humans , Aged , Glomerular Filtration Rate , Creatinine , Kidney/physiology , AlbuminsABSTRACT
Vancomycin (VCM)-induced nephrotoxicity (VIN) is a major side effect in paediatric patients. However, most studies are limited to patients aged 0-18 years. We evaluated the risk factors of VIN in patients aged 0-1 year using Japanese electronic medical record database. We used RWD database which was contained electronic medical records and claims data of approximately 20 million people from 160 medical institutions. We targeted hospitalized patients who were administered VCM between June 2000 and December 2020. VIN was defined by two criteria: Criterion 1 was an increase in serum creatinine (Scr) ≥ 0.5 mg/dL or 50% during VCM treatment period compared to the Scr baseline; and criterion 2 was an increase in Scr ≥50% within seven days or Scr ≥0.3 mg/dL within two days during VCM treatment. The risk factors of VIN were evaluated using multivariate logistic regression analysis. We analysed 446 patients; patients with VIN in Criteria 1 and 2 were 33 and 58, respectively. In Criterion 1, multivariate logistic regression analysis identified four independent factors with p-value <0.05 (VCM concentration ≥20 mg/L, amphotericin B (AMPH-B), piperacillin-tazobactam (TAZ/PIPC), and vasopressor drugs). In Criterion 2, multivariate logistic regression analysis identified concomitant use of vasopressor drugs with p-value <0.05. Therefore, concomitant use of vasopressor drugs was suggested to affect the risk of VIN in patients aged 0-1 year. The findings may help in developing estimation models to assess the risk of VIN in paediatric patients.
Subject(s)
Anti-Bacterial Agents , Vancomycin , Humans , Anti-Bacterial Agents/therapeutic use , East Asian People , Retrospective Studies , Risk Factors , Vancomycin/therapeutic use , Infant, Newborn , InfantABSTRACT
OBJECTIVE: Chemotherapy-induced nausea and vomiting (CINV) and chemotherapy-associated dyspepsia syndrome (CADS) are frequently appearing adverse effects of cisplatin (CDDP)-containing chemotherapy. Antiemetic guidelines suggest that the administration of antacids such as proton pump inhibitors (PPIs) or histamine type-2 receptor antagonists be considered for CADS, although their efficacy for treating these symptoms remains unknown. This study aimed to reveal whether antacids attenuate gastrointestinal symptoms in CDDP-containing chemotherapy. MATERIALS AND METHODS: In total, 138 patients with lung cancer who received ≥ 75 mg/m2 CDDP-containing regimens were enrolled in this retrospective study. Patients were divided into an antacid group including patients administered PPIs or vonoprazan during all chemotherapy periods and controls without antacid administration. The primary endpoint was the comparison of anorexia incidence during the first cycle of chemotherapy. Secondary endpoints were CINV evaluation and risk factor analysis for the incidence of anorexia using logistic regression analysis. RESULTS: The incidence of anorexia during the first cycle was 54.4% in the control group and 60.3% in the antacid group, without significant differences (p = 0.60). The incidence of nausea was also similar between the groups (p = 1.00). Multivariate analysis suggested that antacid administration was not associated with anorexia. CONCLUSION: Baseline antacid administration does not affect gastrointestinal symptoms associated with CDDP-containing treatment in lung cancer.
Subject(s)
Antineoplastic Agents , Lung Neoplasms , Humans , Cisplatin/adverse effects , Antacids/therapeutic use , Antineoplastic Agents/adverse effects , Anorexia/chemically induced , Anorexia/drug therapy , Retrospective Studies , Lung Neoplasms/drug therapy , Vomiting/chemically induced , Vomiting/drug therapy , Vomiting/epidemiology , Nausea/chemically induced , Nausea/drug therapy , Nausea/epidemiologyABSTRACT
PURPOSE: Regorafenib is the first multikinase inhibitor used for metastatic colorectal cancer (mCRC) treatment. Reports regarding other multikinase inhibitors have suggested that the development of hypertension is associated with improved clinical benefits. We aimed to reveal the relationship between the development of severe hypertension and regorafenib efficacy in an mCRC real-world setting. METHODS: Patients with mCRC (n = 100) who received regorafenib were assessed retrospectively. The primary endpoint was a comparison of progression-free survival (PFS) between patients with and without ≥ grade 3 hypertension. The secondary endpoints were overall survival (OS), disease control rate (DCR), and adverse effects. RESULTS: Patients developing ≥ grade 3 hypertension accounted for 30%, and obtained significantly longer PFS than control patients (median PFS of 53 and 56 days, 95% confidence interval [CI] of 46-144 and 49-63 days, respectively; P = 0.04). In contrast, OS and DCR were not statistically different between the groups (P = 0.13 and P = 0.46, respectively). The incidence and severity of adverse effects were not significantly different, except for hypertension. Treatment interruption was significantly more frequent in patients with hypertension (P = 0.04). Multivariate Cox hazard analysis suggested that the development of ≥ grade 3 severe hypertension was an independent factor for improved PFS (adjusted hazard ratio 0.57, 95% CI 0.35-0.93; P = 0.02). In contrast, baseline hypoalbuminemia was associated with a worse PFS (1.85, 1.14-3.01; P = 0.01). CONCLUSION: We have revealed that patients who develop severe hypertension after regorafenib treatment for mCRC have improved PFS. Management of hypertension is important for effective treatment with less burden; therefore, further evaluation is needed.
Subject(s)
Colonic Neoplasms , Colorectal Neoplasms , Hypertension , Rectal Neoplasms , Humans , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/pathology , Progression-Free Survival , Retrospective Studies , Colonic Neoplasms/drug therapy , Rectal Neoplasms/drug therapy , Phenylurea Compounds/adverse effects , Hypertension/chemically induced , Hypertension/drug therapyABSTRACT
BACKGROUND: Immune checkpoint inhibitors (ICIs) are used in cancer immunotherapy; however, they can lead to immune-related adverse events (irAEs) through immune function of patients. Therefore, this meta-analysis aimed to assess the concomitant effect of acid suppressants (ASs) on ICIs, including several subgroup analyses. METHODS: We identified related studies and generated the forest plot. The primary endpoint was defined as the change in progression free survival (PFS) and overall survival (OS) with or without ASs administration. We also evaluated the effect of ASs on the incidence of irAEs. RESULTS: The total hazard ratio (HR) of ASs on PFS with ICI treatment was 1.39 and the 95% confidence interval (95% CI) was 1.21-1.59 (Z: p < 0.00001). Moreover, the total HR of ASs on OS was 1.40 and the 95% CI was 1.21-1.61 (Z: p < 0.00001), suggesting that ASs reduced ICI's therapeutic effect. The total odds ratio (OR) for evaluating the effect of ASs on irAEs was 1.23 with a 95% CI of 0.81-1.88 (Z: p = 0.34). However, ASs significantly worsened acute kidney injury (AKI) (total OR 2.10; 95% CI 1.74-2.53 (Z, p < 0.00001)). Furthermore, although proton pump inhibitors (PPIs) reduced ICI's therapeutic effect, histamine H2-receptor antagonists (H2RAs) did not affect OS. CONCLUSIONS: It was shown that ASs, especially PPIs, reduced ICI's therapeutic effect, while H2RAs had no effect, and ASs did not affect irAEs; however, it is a risk factor for ICIs-induced AKI.
ABSTRACT
BACKGROUND: There is little evidence regarding risk prediction for surgical site infection (SSI) after lower third molar (L3M) surgery. METHODS: We conducted a nested case-control study to develop a multivariable logistic model for predicting the risk of SSI after L3M surgery. Data were obtained from Hokkaido University Hospital from April 2013 to March 2020. Multiple imputation was applied for the missing values. We conducted decision tree (DT) analysis to evaluate the combinations of factors affecting SSI risk. RESULTS: We identified 648 patients. The final model retained the available distal space (Pell & Gregory II [p = 0.05], Pell & Gregory III [p < 0.01]), depth (Pell & Gregory B [p < 0.01], Pell & Gregory C [p < 0.01]), surgeon's experience (3-10 years [p = 0.25], <3 years [p < 0.01]), and simultaneous extraction of both L3M [p < 0.01]; the concordance-statistic was 0.72. The DT analysis demonstrated that patients with Pell and Gregory B or C and simultaneous extraction of both L3M had the highest risk of SSI. CONCLUSIONS: We developed a model for predicting SSI after L3M surgery with adequate predictive metrics in a single center. This model will make the SSI risk prediction more accessible.