Association of oral mucositis induced by anthracycline-cyclophosphamide and subsequent docetaxel treatment for perioperative breast cancer.

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.

30° anteriorly tilted CT for visualizing the drainage pathway of the frontal sinus.

KEY POINTS: The optimal tilt for anteriorly tilted coronal CT was examined. A 30° anteriorly tilted coronal CT best visualized the frontal sinus drainage pathway.

The Time to Spontaneous Drop of Polyglactin 910 (Vicryl) in the Nasal Cavity.

Sutures play a crucial role in closing mucosal incisions during endoscopic nasal surgery. The duration until the spontaneous drop of polyglactin 910 (Vicryl) sutures in the nasal cavity remains uncertain. To investigate this, we examined the medical records of patients who underwent septoplasty, inferior turbinate reduction, or endoscopic modified medial maxillectomy with polyglactin 910 sutures. The sutures were counted and monitored during follow-up visits, and removal occurred only if patients reported discomfort. In our study of 124 patients, a total of 453 sutures were placed during surgery. Eighteen sutures had to be intentionally removed due to discomfort. Importantly, no surgical site infections were observed during the follow-up period. We found that sutures on the lateral nasal wall persisted longer than those on the nasal septum, with respective half-lives of 70 days and 64 days (p = 0.0071). In conclusion, using polyglactin 910 sutures in nasal surgery and allowing them to dissolve naturally in the submucosa is an effective approach. The sutures exhibit longer persistence on the lateral nasal wall compared to the nasal septum.

Development of an Evaluation System Using Intestinal Organoids for Drug Efflux Transport Analysis by an Imaging Approach.

There are several in vitro systems that enable evaluation of the absorption direction, but there are few quantitative systems that enable easy evaluation of the excretion direction. Enteroids, organoids derived from intestine, have been frozen and passaged for various research. But it is not clear how the freezing and passaging affect the expression and function of transporters. We investigated the effects of passage and cryopreservation of enteroids. We focused on P-gp (P-glycoprotein) and compared the transfer rates of rhodamine 123 (Rh123) into the lumen of enteroids with and without a P-gp inhibitor. mRNA expression levels did not change significantly before and after passage and cryopreservation. Accumulation of Rh123 in the lumen of enteroids was observed. With some P-gp inhibitors, excretion of Rh123 into the lumen of enteroids was inhibited and the nonexcreted Rh123 accumulated in enteroids epithelial cells. The transfer rate of Rh123 into the lumen of enteroids with a P-gp inhibitor was significantly decreased compared to that of without a P-gp inhibitor. Before and after passage and cryopreservation, the transfer rate was almost the same as that of primary cultured enteroids. We succeeded in easily evaluating whether a component is a substrate of P-gp using enteroids.

Evaluation of the impact of systemic dexamethasone dosage on docetaxel-induced hand-foot syndrome in patients with breast cancer.

Hand-foot syndrome (HFS) is a frequently occurring and treatment-requiring adverse effect of docetaxel. We previously reported that systemic dexamethasone (DEX) prevents the other docetaxel-induced adverse inflammatory effects in a dose-dependent manner. This study aimed to evaluate the dose-dependent efficacy of systemic DEX in attenuating HFS in patients with breast cancer receiving docetaxel. Patients with breast cancer receiving docetaxel (75 mg/m2)-containing regimens (n = 111) were divided into 4 and 8 mg/day DEX groups, with each DEX dose administered on days 2-4, and analyzed retrospectively. Development of all-grade HFS in all treatment cycles was significantly lower in the 8 mg group (50.0%) than in the 4 mg group (73.0%, P = 0.03), with primary endpoint accomplishment. Moreover, its development in the first cycle was also lower in the 8 mg group than in the 4 mg group. These results were confirmed in a propensity score-matched population. Logistic regression analysis suggested higher DEX dosage as an independent preventive factor (adjusted odds ratio 0.35; 95% confidence interval 0.14-0.86, P = 0.02 for all cycles; 0.26, 0.11-0.63, P = 0.003 for the first cycle). Our study suggests that systemic DEX prevents the occurrence of docetaxel-induced HFS in patients with breast cancer in a dose-dependent manner in a real-world setting.

Propriety of various examinations for subjective symptoms of olfactory disorders.

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.

Factors influencing residual plus moist HS-W calcium alginate packing material after endoscopic sinus surgery.

OBJECTIVE: This study aims to evaluate the presence of residual Plus Moist HS-W (PM), a novel calcium alginate packing material, during the initial postoperative visit following endoscopic sinus surgery. The research aims to identify factors that influence the quantity of remaining PM. METHODS: A retrospective review of medical records was conducted for patients who underwent middle meatus packing with PM. RESULTS: A total of fifty-two patients (representing 92 sides of paranasal sinuses) were included in the analysis. The remaining PM was classified as follows: absent (0) in 41 out of 92 cases, minimal (1) in 22 out of 92 cases, moderate (2) in 15 out of 92 cases, and substantial (3) in 14 out of 92 cases. Notably, all three patients who underwent Draf III surgery exhibited a significant amount of PM during their initial visit, with two patients classified as grade 2 and one patient as grade 3. Other factors investigated were found to be unrelated to the persistence of PM. Removal of all PM was achieved effortlessly using suction under flexible endoscopy. CONCLUSION: This study highlights the efficacy of PM in post-endoscopic sinus surgery care. It is important to limit an amount of PM, particularly in Draf III procedures.

Evaluation of Efficacy of Adding Aprepitant to Palonosetron and Dexamethasone in Carboplatin and Etoposide Therapy.

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.

Anteriorly Tilted Coronal CT of Paranasal Sinuses for Endoscopic Sinus Surgery.

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.

Evaluation of the risk factors for the failure of a single prophylactic dose of anticholinergic drugs for irinotecan-induced cholinergic symptoms.

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.

Immunoregulatory Effects of Elemental Diet and Its Ingredient, Tryptophan, via Activation of the Aryl Hydrocarbon Receptor in Mice.

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.

Impact of preexisting proteinuria on the development of regorafenib-induced problematic proteinuria in real-world metastatic colorectal cancer treatment.

Regorafenib is the first multikinase inhibitor for treating metastatic colorectal cancer (mCRC). Proteinuria is a frequently encountered adverse effect, regardless of prior administration of vascular endothelial growth factor inhibitors. Herein, we aimed to assess the impact of baseline preexisting proteinuria on regorafenib-induced problematic proteinuria during real-world mCRC therapy. Patients with mCRC receiving regorafenib (n = 100) were retrospectively assessed and divided into control and preexisting proteinuria (baseline grade of 1-2) groups. The primary endpoint was the development of grade ≥ 2 (grade ≥ 3 in case of baseline grade 2 patients) proteinuria. Propensity score-matching was performed to confirm the robustness of primary analyses. Defined proteinuria occurred in 30.7 and 57.9% of patients in the control and preexisting proteinuria groups, respectively, with significant differences in the all-patient population (P = 0.01). The preexisting proteinuria group exhibited significant defined proteinuria development within 7 days of regorafenib initiation, grade ≥ 3 symptoms, and treatment suspension owing to proteinuria. Similar results were obtained in the propensity score-matched population. According to multivariate logistic regression analysis, baseline proteinuria was a singular risk factor for defined proteinuria development (adjusted odds ratio; 3.76, 95% confidence interval; 1.45-9.75, P = 0.007). Collectively, our study revealed that patients with preexisting proteinuria develop regorafenib-induced proteinuria degradation.

Platelets Affect the Activity of Amino Acid Transporter SNAT4 in HuH-7 Human Hepatoma Cells.

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.

Evaluation of Prediabetes in Cisplatin-induced Nephrotoxicity in the Short Hydration Method: A Subgroup Analysis.

BACKGROUND/AIM: Cisplatin-induced nephrotoxicity (CIN) is one of the most attention-requiring adverse effects. We have reported that diabetes mellitus significantly increases the incidence of CIN in a short hydration method in real-world lung cancer treatment. However, the effect of prediabetes on CIN development remains unclear. This study investigated whether patients with prediabetes exhibit CIN at a greater rate during real-world cisplatin-including treatments as a subgroup analysis. PATIENTS AND METHODS: This retrospective observational study enrolled patients with lung cancer receiving cisplatin treatment (≥75 mg/m2) from May 2014 to January 2021 (n=169). Patients were divided into a prediabetes group (baseline HbA1c 5.7-6.4%) and a control group (baseline HbA1c <5.7%). The primary endpoint of this study was the incidence of CIN in all treatment cycles between the two groups. We also assessed variations in serum creatinine (SCr) levels and creatinine clearance (CCr). RESULTS: CIN occurred in 4.7% of controls and 8.3% of patients with prediabetes in all cycles, with no significant difference (p=0.37). In contrast, variation of SCr levels and CCr was significantly worse in the prediabetes group [median variation level (range) 0.11 mg/dl (-0.11-0.46 mg/dl) and 0.12 mg/dl (-0.02-1.08 mg/d) in controls and prediabetes, p=0.04 for SCr; -12.9 ml/min (-54.1-4.9 ml/min) and -16.3 ml/min (-49.4-3.0 ml/min), p=0.02 for CCr, respectively]. These results were also confirmed during the first cycle of treatment. CONCLUSION: Patients with prediabetes did not develop problematic CIN, although they exhibited significant increases in SCr and decreases in CCr.

Significantly Delayed Development of Polyarthritis with Active Tenosynovitis after Possible Temporary Neutropenic Immune-Related Adverse Events Caused by Atezolizumab Treatment: A Novel Case Report.

Immune checkpoint inhibitors have drastically improved cancer treatment. However, they may induce immune-related adverse events (irAEs). Here, we report a case of significantly delayed rheumatic irAEs (Rh-irAEs) with prior possible temporary neutropenic irAEs in a patient with atezolizumab-treated non-small-cell lung cancer and its management. A man in his sixties received atezolizumab monotherapy as the sixth-line treatment. He experienced an infusion-related reaction (fever) during the first cycle. On day 22 of cycle 2, grade 4 neutropenia suddenly appeared, but it disappeared on the next day. Cycle 3 was initiated after seven days; the patient did not exhibit any symptoms for approximately 500 days. However, on day 534 (day 1 of cycle 21), the patient complained of pain in the shoulders, back, and wrists. On day 644, the shoulder and back pain worsened with obvious swelling of the fingers. We thus suspended treatment and consulted a rheumatologist. A diagnosis of polyarthritis with active tenosynovitis was made based on joint ultrasound and laboratory tests. Prednisolone 15 mg attenuated the symptoms, allowing suspension of analgesics; however, dose reduction from 15 mg/day was difficult because of symptom flares. Finally, iguratimod 25 mg twice daily was initiated on day 764; prednisolone was reduced to 10 mg without flares, and its dosage was slowly reduced to 5 mg/day. Although irAEs exhibit multisystem features, delayed development of polyarthritis with active tenosynovitis after possible temporary neutropenic irAEs is rare. Thus, irAEs need to be monitored for a long time in patients with suspected irAE development even if it appears transiently.

Decrease in Mycophenolic Acid Plasma Level by Sacubitril/Valsartan in a Lupus Nephritis Patient: A Case Report.

Introduction: Mycophenolate mofetil (MMF), an inactive prodrug of mycophenolic acid (MPA), is an immunosuppressive drug used widely in the treatment of lupus nephritis. In this case report, the area under the blood concentration time curve (AUC) of MPA was significantly decreased by the concomitant use of sacubitril/valsartan. Case Presentation: The patient was a man in his 40s with a diagnosis of lupus nephritis class IVa/c+V. MMF dose was 1.5 g/day at admission, and AUC of MPA on day 14 was 25.1 µg⋅h/mL. Owing to poor blood pressure control, sacubitril/valsartan was initiated at 97/103 mg/day on day 29. On day 37, AUC of MPA was significantly decreased to 8.7 µg⋅h/mL, suggesting drug interaction with the newly initiated sacubitril/valsartan. Sacubitril/valsartan was decreased to 49/51 mg/day, and AUC of MPA on day 67 was 37.6 µg⋅h/mL, achieving the target range. The final MMF dose was set at 1.75 g/day. A possible mechanism of drug interaction between sacubitril/valsartan and MPA involves an organic anion transporting polypeptide (OATP). The inhibition of OATPs by sacubitril may have interrupted the enterohepatic circulation of MPA, resulting in a lower plasma concentration. Conclusion: Since lupus nephritis is often associated with hypertension, the drug interaction observed in this report may also occur in other cases. However, it is impossible to conclude that the decrease in plasma MPA levels was due to the concomitant use of sacubitril/valsartan, and more cases and basic findings are needed.

Epidemiology of postoperative bleeding after endoscopic nasal and sinus surgery and factors associated with bleeding.

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.

Comparison of the incidence of nausea and vomiting between linezolid and vancomycin using claims database: a retrospective cohort study.

BACKGROUND: Nausea and vomiting during linezolid therapy have been reported as part of safety analyses in clinical trials. We have previously examined the incidence of vomiting during linezolid therapy (18.1%). A previous study conducted at a single hospital showed low external validity. It is necessary to verify whether these results can be reproduced using generalizable data sources. AIM: To evaluate the incidence of nausea and vomiting during linezolid therapy compared with vancomycin using a Japanese claims database. METHOD: Patients administered linezolid or vancomycin were selected from the database between January 2005 and June 2017. The primary endpoint was the comparison of nausea and vomiting between the linezolid and vancomycin groups. We conducted propensity score matching (PSM) to adjust for patient characteristics. To assess risk factors for nausea and vomiting, logistic regression was conducted as the secondary endpoint. We defined nausea and vomiting as the first prescription of antiemetics during linezolid or vancomycin therapy as a surrogate endpoint. RESULTS: In total, 1215 patients were enrolled. After PSM, the number of patients in the linezolid and vancomycin groups was 241. Nausea and vomiting were observed in 11.2% and 5.0% of patients in the linezolid and vancomycin groups, respectively (p < 0.05). Linezolid administration was extracted as a risk factor for nausea and vomiting (odds ratio, 2.09; 95% confidence interval, 1.02-4.30). CONCLUSION: This study clarified the relationship between linezolid and nausea and vomiting using a Japanese claims database. Further studies are required to elucidate the unknown mechanisms of linezolid-induced nausea and vomiting.

Evaluation of the additional prophylactic effect of topical steroid ointment to systemic minocycline against anti-epidermal growth factor antibody-induced skin toxicities in metastatic colorectal cancer treatment.

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.

Palonosetron for prevention of delayed chemotherapy-induced nausea and vomiting in pediatric patients: a meta-analysis.

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.