Predicting Trabectedin Efficacy in Soft Tissue Sarcoma: Inflammatory Biomarker Analysis.

BACKGROUND/AIM: Trabectedin is used as a treatment for advanced-stage soft tissue sarcomas (STSs), particularly liposarcoma and leiomyosarcoma. Aside from its direct effect on tumor cells, trabectedin can affect the immune system in the tumor microenvironment. This study aimed to evaluate whether inflammatory biomarkers predict trabectedin efficacy in STSs. PATIENTS AND METHODS: We retrospectively reviewed the clinical features and outcomes of patients with STS treated with trabectedin at our institution between 2016 and 2020. The neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), and systemic inflammation response index (SIRI=neutrophil × monocyte/lymphocyte) were calculated based on the blood samples obtained prior to trabectedin treatment initiation. Analyses of overall survival (OS) and progression-free survival (PFS) were performed according to various factors. RESULTS: Of the 101 patients identified, 54 had L-sarcoma (leiomyosarcoma: 30; liposarcoma: 24), and 47 had other types of STSs. Elevated SIRI, NLR, PLR, LMR, and C-reactive protein (CRP) were associated with worse PFS (p<0.001, p=0.008, p=0.027, p=0.013, and p<0.001, respectively) according to the results of the univariate analysis. Multivariate analysis showed that elevated SIRI, other histology, and CRP were associated with poor PFS (p=0.007, p=0.008, and p=0.029, respectively). In addition, the multivariate analysis of OS showed that SIRI was an independent prognostic factor (hazard ratio=2.16, p=0.006). CONCLUSION: Pretreatment SIRI can be considered a biomarker for the prognostic prediction of patients with STS treated with trabectedin.

Administration of Intravenous Lipid Emulsion for Dextromethorphan Poisoning with Serotonin Syndrome: A Case Report.

Dextromethorphan (DXM) is used to treat colds and coughs; however, it can cause central nervous system symptoms, such as severe serotonin syndrome (SS). To our knowledge, there is no specific treatment for severe DXM poisoning, and there are no reports on the clinical use of intravenous lipid emulsion (ILE) for its treatment. Herein, we report a case of severe DXM poisoning with SS that was successfully treated with ILE. An older adolescent male visited the emergency department 1 h after ingesting 4500 mg of DXM orally. Physical examination revealed generalized convulsions, muscle rigidity, mydriasis (8.0/8.0 mm), and flushed skin, with a Glasgow Coma Scale score of 8 (E3V1M4). Severe DXM poisoning with SS was diagnosed. The patient was intubated and administered midazolam for continuous convulsions and SS. Activated charcoal was also administered, and body surface cooling was performed. After an 11 h intensive care unit admission, SS with mydriasis (6.0/6.0 mm) did not improve. Subsequently, 1100 mL of 20% soybean oil was injected as an ILE. Mydriasis improved (3.5/3.5 mm) 30 min after ILE administration; simultaneously, blood DXM concentration rapidly increased approximately two-fold. After discontinuing midazolam, the patient's consciousness signs improved, and he was weaned off the ventilator. SS was cured with no recurrence of convulsions. In cases of DXM poisoning with severe central nervous system disorders, such as SS, ILE treatment can potentially be an effective therapeutic option. For oral overdose cases, where the drug may remain in the intestinal tract, measures such as administering activated charcoal should be taken before administering ILE.

Incidence of skeletal-related events in patients with Ewing sarcoma: An observational retrospective study in Japan.

BACKGROUND: Skeletal-related events (SREs), including the pathological fracture, surgical treatment or radiation of bone lesions, malignant spinal cord compression, hypercalcemia, are important considerations when managing metastatic bone tumors; however, owing to their rarity, the incidence of SREs in patients with Ewing sarcoma remains unknown. METHODS: We retrospectively reviewed the clinical data from 146 patients with Ewing sarcoma treated at a single institution from 2005 to 2019. The median age at diagnosis was 22.7 years. Fifty patients (34.2%) had metastatic disease at diagnosis. The primary outcome was the SRE-free rate among patients with Ewing sarcoma. Moreover, we identified the risk factors for SREs using univariate or multivariate analyses. RESULTS: During the observational period (median, 2.6 years), SREs occurred in 23 patients. Radiation to the bone, malignant spinal cord compression, and hypercalcemia were documented as the initial SREs in 12 patients (52.2%), 10 patients (43.5%), and one patient (4.3%), respectively. The SRE-free rate was 94.2 ± 2.0, 87.3 ± 3.0, and 79.6 ± 3.8% at 1, 2, and 3 years after the initial visit, respectively. Multivariate analysis revealed bone metastasis at diagnosis (hazard ratio [HR] = 4.41, p = 0.007), bone marrow invasion (HR = 34.08, p < 0.001), and local progression or recurrence after definitive treatment (HR = 3.98, p = 0.012) as independent risk factors for SREs. CONCLUSIONS: SREs are non-rare events that can occur during the treatment course for Ewing sarcoma, with an especially high incidence of malignant spinal cord compression. Patients with metastatic disease at diagnosis, especially in the bone or bone marrow, or with local progression or recurrence after definitive treatment, should be carefully monitored for the occurrence of SREs. The most effective methods to monitor the occurrence of SREs and new preventative therapies for SREs should be investigated in the future.

Adenovirus pneumonia mimicking osimertinib-induced pneumonitis in a patient with advanced NSCLC with EGFR mutation: A case report.

Drug-related pneumonitis (DRP) caused by epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) is a fatal adverse event in patients with EGFR-mutant non-small cell lung cancer (NSCLC). The diagnosis of DRP is based on radiological findings, the temporal association of presentation with the initiation of a systemic therapeutic agent, and the exclusion of other likely causes. Here we report a case in which severe adenoviral pneumonia mimicking DRP occurred during treatment with osimertinib, and osimertinib was successfully resumed after recovery from adenoviral pneumonia.

Concomitant use of hydroxyzine and haloperidol did not worsen delirium in patients with cancer: A multicenter, retrospective, observational study.

OBJECTIVES: There is concern that hydroxyzine exacerbates delirium, but a recent preliminary study suggested that the combination of haloperidol and hydroxyzine was effective against delirium. This study examined whether the concomitant use of hydroxyzine and haloperidol worsened delirium in patients with cancer. METHODS: This retrospective, observational study was conducted at 2 general hospitals in Japan. The medical records of patients with cancer who received haloperidol for delirium from July to December 2020 were reviewed. The treatments for delirium included haloperidol alone or haloperidol combined with hydroxyzine. The primary outcome was the duration from the first day of haloperidol administration to the resolution of delirium, defined as its absence for 2 consecutive days. The time to delirium resolution was analyzed to compare the haloperidol group and hydroxyzine combination group using the log-rank test with the Kaplan-Meier method. Secondary outcomes were (1) the total dose of antipsychotic medications, including those other than haloperidol (measured in chlorpromazine-equivalent doses), and (2) the frequencies of detrimental incidents during delirium, specifically falls and self-removal of drip infusion lines. The unpaired t-test and Fisher's exact test were used to analyze secondary outcomes. RESULTS: Of 497 patients who received haloperidol, 118 (23.7%) also received hydroxyzine. No significant difference in time to delirium resolution was found between the haloperidol group and the hydroxyzine combination group (log-rank test, P = 0.631). No significant difference between groups was found in either chlorpromazine-equivalent doses or the frequency of detrimental incidents. SIGNIFICANCE OF RESULTS: This study showed that the concomitant use of hydroxyzine and haloperidol did not worsen delirium in patients with cancer.

Label-free cell detection of acute leukemia using ghost cytometry.

Early diagnosis and prompt initiation of appropriate treatment are critical for improving the prognosis of acute leukemia. Acute leukemia is diagnosed by microscopic morphological examination of bone marrow smears and flow cytometric immunophenotyping of bone marrow cells stained with fluorophore-conjugated antibodies. However, these diagnostic processes require trained professionals and are time and resource-intensive. Here, we present a novel diagnostic approach using ghost cytometry, a recently developed high-content flow cytometric approach, which enables machine vision-based, stain-free, high-speed analysis of cells, leveraging their detailed morphological information. We demonstrate that ghost cytometry can detect leukemic cells from the bone marrow cells of patients diagnosed with acute lymphoblastic leukemia and acute myeloid leukemia without relying on biological staining. The approach presented here holds promise as a precise, simple, swift, and cost-effective diagnostic method for acute leukemia in clinical practice.

Clinical characteristics of primary cutaneous and subcutaneous Ewing sarcoma.

OBJECTIVE: Given the rarity of cutaneous/subcutaneous Ewing sarcoma, their clinical characteristics remain poorly understood. In this study, we aimed to analyse the clinical characteristics of patients with cutaneous/subcutaneous Ewing sarcoma and review the treatment strategy. METHODS: We reviewed the clinical data of 154 patients with Ewing sarcoma who were treated at our hospital between 2005 and 2019. Amongst these patients, 21 patients with cutaneous/subcutaneous Ewing sarcoma were analysed. As a basic strategy, patients with localized disease received intensive chemotherapy (vincristine-doxorubicin-cyclophosphamide/ifosfamide-etoposide), followed by definitive surgery with or without radiotherapy. In total, 15 patients underwent pre-diagnostic resection with macroscopic residue (seven patients) or non-macroscopic residue (eight patients) before intensive chemotherapy. RESULTS: The median tumour length of the measurable lesions was 3.2 cm, and the ratio of metastasis was significantly lower than the Ewing sarcoma of other anatomical sites (10% vs. 37%, P = 0.013). Despite the pre-diagnostic resection, local recurrence after additional resection and/or adjuvant radiotherapy did not occur in any of the patients with localized disease. Overall survival was significantly higher in patients with cutaneous/subcutaneous Ewing sarcoma than in patients with Ewing sarcoma of other anatomical sites (hazard ratio = 0.33, P = 0.013). The event-free survival rate of cutaneous/subcutaneous Ewing sarcoma was also superior to that of Ewing sarcoma of other anatomical sites (hazard ratio = 0.35, P = 0.01). CONCLUSIONS: Patients with cutaneous/subcutaneous Ewing sarcoma may have better prognosis than those with Ewing sarcoma at other anatomical sites. Although pre-diagnostic resection without appropriate investigations is not recommended, local control may be recovered by using a combination of additional resection, chemotherapy and radiotherapy.

Effects of reduced edoxaban administration on bleeding risk and D-dimer levels in patients wearing elastic stockings after total hip arthroplasty: A retrospective cohort study.

OBJECTIVE: Edoxaban is sometimes given at reduced doses when used concomitantly with physical prophylaxis to prevent symptomatic venous thromboembolism (VTE) after total hip arthroplasty (THA). This study aimed to evaluate the safety of reduced doses of edoxaban administered independent of the dose-reduction criteria and their effects on D-dimer levels after THA in Japanese patients. MATERIALS AND METHODS: This study enrolled 22 patients who received edoxaban 30 mg/day and 45 patients who received edoxaban 15 mg/day with dose adjustment as a standard-dose group, and 110 patients who received edoxaban 15 mg/day without dose adjustment as a low-dose group. The incidence of bleeding events was then compared between groups with patients wearing elastic stockings. Multivariate regression analysis was also performed to examine the effect of edoxaban administration on D-dimer levels after THA. RESULTS: The incidence of bleeding events after THA did not differ significantly between groups. In the multivariate model, dose reduction of edoxaban did not correlate with D-dimer levels on postoperative days 7 and 14, but higher D-dimer levels at postoperative days 7 and 14 correlated significantly with longer duration of surgery (odds ratio (OR) 1.66, 95% confidence interval (CI) 1.20 - 2.29, p = 0.002; OR 1.63, 95% CI 1.17 - 2.29, p = 0.004, respectively). CONCLUSION: These results suggest that information on the duration of surgery may be useful in the pharmaceutical management in edoxaban drug prophylaxis combined with physical prophylaxis after THA in Japanese patients.

Preferential formation of specific hexose and heptose in the formose reaction under microwave irradiation.

To realize sustainable societies, the production of organic compounds not based on fossil resources should be developed. Thus, C1 chemistry, utilizing one-carbon compounds as starting materials, has been of increasing importance. In particular, the formose reaction is promising because the reaction produces sugars (monosaccharides) from formaldehyde under basic conditions. On the other hand, since microwave (MW) induces the rotational motion of molecules, MW irradiation often improves the selectivity and efficiency of reactions. In this study, the formose reaction under MW irradiation was thus investigated under various conditions. The formose reaction proceeded very fast using 1.0 mol per kg formaldehyde and 55 mmol per kg calcium hydroxide (Ca(OH)2) as a catalyst at a high set temperature (150 °C) for a short time (1 min) to form preferentially specific hexose and heptose. The major products were isolated by thin layer chromatography and characterized by mass spectroscopy and NMR. These characterization data elucidated that the hexose and heptose were 2-hydroxymethyl-1,2,4,5-tetrahydroxy-3-pentanone (C6*) and 2,4-bis(hydroxymethyl)-1,2,4,5-tetrahydroxy-3-pentanone (C7*), respectively. On the basis of these observations, as well as density functional theory calculations, a plausible reaction pathway was also discussed; once 1,3-dihydroxyacetone is formed, consecutive aldol reactions favorably occur to form C6* and C7*.

Successful Treatment of Amoxapine-Induced Intractable Seizures With Intravenous Lipid Emulsion.

BACKGROUND: Amoxapine is a second-generation tricyclic antidepressant with a greater seizure risk than other antidepressants. If administered in large amounts, amoxapine can cause severe toxicity and death. Therefore, it is necessary to terminate seizures immediately if amoxapine toxicity occurs. However, intractable seizures often occur in these patients. We describe a case of intractable seizures caused by amoxapine poisoning, in which intravenous lipid emulsion (ILE) was used successfully. CASE REPORT: A 44-year-old woman with a history of depression ingested 3.0 g of amoxapine during a suicide attempt. Although she was initially treated with intravenous diazepam, her seizures persisted. Levetiracetam and phenobarbital were then administered, but seizures persisted. Hence, ILE was injected for over 1 min. At 2 min after ILE administration, the patient's status seizures ceased. Recurrence of seizures was observed 30 min after ILE, and the seizures disappeared after re-administration of ILE. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: ILE may be effective in amoxapine intoxication. Emergency physicians may consider ILE as an adjunctive therapy for amoxapine poisoning with a high mortality rate. ILE should be implemented carefully with monitoring of total dosage and adverse events.

Artificial Intelligence-Powered Prediction of ALK Gene Rearrangement in Patients With Non-Small-Cell Lung Cancer.

PURPOSE: Several studies reported the possibility of predicting genetic abnormalities in non-small-cell lung cancer by deep learning (DL). However, there are no data of predicting ALK gene rearrangement (ALKr) using DL. We evaluated the ALKr predictability using the DL platform. MATERIALS AND METHODS: We selected 66 ALKr-positive cases and 142 ALKr-negative cases, which were diagnosed by ALKr immunohistochemical staining in our institution from January 2009 to March 2019. We generated virtual slide of 300 slides (150 ALKr-positive slides and 150 ALKr-negative slides) using NanoZoomer. HALO-AI was used to analyze the whole-slide imaging data, and the DenseNet network was used to build the learning model. Of the 300 slides, we randomly assigned 172 slides to the training cohort and 128 slides to the test cohort to ensure no duplication of cases. In four resolutions (16.0/4.0/1.0/0.25 µm/pix), ALKr prediction models were built in the training cohort and ALKr prediction performance was evaluated in the test cohort. We evaluated the diagnostic probability of ALKr by receiver operating characteristic analysis in each ALKr probability threshold (50%, 60%, 70%, 80%, 90%, and 95%). We expected the area under the curve to be 0.64-0.85 in the model of a previous study. Furthermore, in the test cohort data, an expert pathologist also evaluated the presence of ALKr by hematoxylin and eosin staining on whole-slide imaging. RESULTS: The maximum area under the curve was 0.73 (50% threshold: 95% CI, 0.65 to 0.82) in the resolution of 1.0 µm/pix. In this resolution, with an ALKr probability of 50% threshold, the sensitivity and specificity were 73% and 73%, respectively. The expert pathologist's sensitivity and specificity in the same test cohort were 13% and 94%. CONCLUSION: The ALKr prediction by DL was feasible. Further study should be addressed to improve accuracy of ALKr prediction.

Lobe-specific nodal dissection with intraoperative frozen section analysis for clinical stage-I non-small cell lung cancer: a validation study by propensity score matching.

OBJECTIVE: Lobe-specific nodal dissection (LND) is increasingly used for non-small cell lung cancer (NSCLC) in Japan; however, its treatment validity remains unclarified. Since 2013, LND has been used as a standard procedure for clinical stage-I (c-stage-I) NSCLC at our institution. We aimed to evaluate its validity using intraoperative frozen section analysis (FSA) for c-stage-I NSCLC. METHODS: The participants comprised patients with NSCLC who underwent LND between 2013 and 2016 (n = 307) or systematic nodal dissection (SND) between 2002 and 2013 (n = 367) for c-stage-I disease. FSA was routinely performed in LND to examine at least three stations. Outcomes were compared between the LND and SND groups. Patients in whom LND was converted to SND due to metastasis on FSA of the sampled lymph node were still categorized into the LND group, i.e., intention-to-treat analysis. The prognostic impact was compared using propensity score matching. RESULTS: The rate of conversion from LND to SND was 10.4%. Of the patients converted to SND, 12.5% had metastases outside the LND area. False-negative N2 results were detected in only 0.7% of the LND group patients after FSA. After matching, each group had 220 patients. There were no significant between-group differences in the lymph-node recurrence rate (7% vs. 6%), 5-year recurrence-free survival (80.1% vs. 79.0%), and overall survival (90.4% vs. 90.3%). CONCLUSIONS: LND with intraoperative FSA is a valid modality that could serve as a standard surgical procedure for c-stage-I NSCLC. Intraoperative FSA may lower the residual lymph-node metastasis risk in LND.

Incidence and risk factors for hyperkalaemia in patients treated for COVID-19 with nafamostat mesylate.

WHAT IS KNOWN AND OBJECTIVE: Nafamostat mesylate (NM) is used clinically in combination with antiviral drugs to treat coronavirus disease (COVID-19). One of the adverse events of NM is hyperkalaemia due to inhibition of the amiloride-sensitive sodium channels (ENaC). The incidence and risk factors for hyperkalaemia due to NM have been studied in patients with pancreatitis but not in COVID-19. COVID-19 can be associated with hypokalaemia or hyperkalaemia, and SARS-CoV-2 is thought to inhibit ENaC. Therefore, frequency and risk factors for hyperkalaemia due to NM may differ between COVID-19 and pancreatitis. Hyperkalaemia may worsen the respiratory condition of patients. The objective of this study was to determine the incidence and risk factors for hyperkalaemia in COVID-19 patients treated with favipiravir, dexamethasone and NM. METHODS: This retrospective study reviewed the records of hospitalized COVID-19 patients treated with favipiravir and dexamethasone, with or without NM, between March 2020 and January 2021. Multivariable logistic regression analysis was performed to identify the risk factors for hyperkalaemia. RESULTS AND DISCUSSION: Of 45 patients who received favipiravir and dexamethasone with NM for the treatment of COVID-19, 21 (47%) experienced hyperkalaemia. The duration of NM administration was a significant predictor of hyperkalaemia (odds ratio: 1.55, 95% confidence interval: 1.04-2.31, p = 0.031). The receiver-operating characteristic curve analysis determined that the cut-off value for predicting the number of days until the onset of hyperkalaemia was 6 days and the area under the curve was 0.707. WHAT IS NEW AND CONCLUSION: This study revealed that the incidence of hyperkalaemia is high in patients treated for COVID-19 with NM, and that the duration of NM administration is a key risk factor. When NM is administered for the treatment of COVID-19, it should be discontinued within 6 days to minimize the risk of hyperkalaemia.

Preventive effect of rebamipide on NSAID-induced lower gastrointestinal tract injury using FAERS and JADER.

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for their antipyretic, analgesic, and anti-inflammatory properties. However, various aspects of NSAID-induced lower gastrointestinal tract injury remain unclear, and effective prophylaxis has not been established. Based on its pharmacological effect and clinical trials, rebamipide may prevent lower gastrointestinal tract injury, although this evidence is limited by the small scale of trials. The present study used the FDA Adverse Event Reporting System (FAERS) and the Japanese Adverse Event Reporting Database (JADER) to assess the efficacy of rebamipide in combination with loxoprofen and diclofenac in preventing NSAID-induced lower gastrointestinal tract injury. The calculated reporting odds ratio and 95% confidence interval (CI) for rebamipide in combination with loxoprofen and diclofenac were 1.15 (95% CI 0.88-1.51) and 1.28 (95% CI 0.82-2.01) for FAERS, and 0.50 (95% CI 0.35-0.71) and 0.43 (95% CI 0.27-0.67) for JADER, respectively. No signal was detected when combining drugs. These results suggest a prophylactic effect of rebamipide on NSAID-induced lower gastrointestinal tract injury.

Elevated INR in a COVID-19 patient after concomitant administration of favipiravir and warfarin: A case report.

WHAT IS KNOWN AND OBJECTIVE: Favipiravir is a promising treatment candidate for managing coronavirus disease 2019 (COVID-19). Warfarin has many drug interactions, but no interactions with favipiravir have been reported. CASE SUMMARY: Our patient was taking warfarin for deep vein thrombosis. The international normalized ratio (INR) was stable (1.65 to 2.0); however, it increased to 4.63 after administering favipiravir. The patient had no other factors justifying this change. WHAT IS NEW AND CONCLUSION: Favipiravir and warfarin might have previously unidentified drug interactions that elevated the INR. Therefore, INR must be closely monitored when they are concomitantly administered in COVID-19 patients.

Efficacy of vonoprazan against bleeding from endoscopic submucosal dissection-induced gastric ulcers under antithrombotic medication: A cross-design synthesis of randomized and observational studies.

Vonoprazan, a potassium-competitive acid blocker, is expected to be superior to proton pump inhibitors (PPIs) in preventing post-endoscopic submucosal dissection (ESD)-induced gastric bleeding. However, the results of randomized controlled trials (RCTs) and observational studies on the efficacy of vonoprazan have been inconsistent. This study aimed to evaluate the effectiveness of vonoprazan in antithrombotic drug users, a population that has been excluded from RCTs. Treatment effects were assessed using cross-design synthesis, which can be adjusted for differences in study design and patient characteristics. We used data from an RCT in Japan (70 patients in the vonoprazan group and 69 in the PPI group) and an observational study (408 patients in the vonoprazan group and 870 in the PPI group). After matching, among the antithrombotic drug users in the observational study, post-ESD bleeding was noted in 8 out of 86 patients in the vonoprazan group and 18 out of 86 patients in the PPI group. After pooling the data from the RCT and observational study, the risk difference for antithrombotic drug users was -14.6% (95% CI: -22.0 to -7.2). CDS analysis suggested that vonoprazan is more effective than PPIs in preventing post-ESD bleeding among patients administered antithrombotic medications.

A case report of super responder of critical COVID-19 pneumonia.

This report presents a case of a 74-year-old man who showed dramatic therapeutic response to treatment of coronavirus infectious disease-19 (COVID-19) pneumonia. He reported four-day history of sustained fever and acute progressive dyspnea. He developed severe respiratory failure, underwent urgent endotracheal intubation and showed marked elevation of inflammatory and coagulation markers such as c-reactive protein (CRP), ferritin, lactate dehydrogenase (LDH) and D-dimer. Chest computed tomography (CT) demonstrated diffuse consolidation and ground glass opacity (GGO). We diagnosed critical COVID-19 pneumonia with detailed sick contact history and naso-pharyngeal swab of a reverse-transcriptase-polymerase-chain reaction (RT-PCR) assay testing. He received anti-viral drug, anti-interleukin (IL-6) receptor antagonist and intravenous methylprednisolone. After commencing combined intensive therapy, he showed dramatic improvement of clinical condition, serum biomarkers and radiological findings. Early diagnosis and rapid critical care management may provide meaningful clinical benefit even if severe case. J. Med. Invest. 68 : 192-195, February, 2021.

Effects of Palonosetron on Nausea and Vomiting Induced by Multiple-Day Chemotherapy: A Retrospective Study.

Patients who undergo multiple-day chemotherapy sessions experience hard-to-treat nausea and vomiting. Currently, there is no effective standard treatment for this condition. This study compared the preventive effect of first-generation 5-hydroxytryptamine 3 receptor antagonists (5-HT3 RAs) and second-generation 5-HT3 RAs palonosetron in multiple-day chemotherapy-induced nausea and vomiting. The design of this study was a retrospective case-control study of patients who received a five-day cisplatin-based chemotherapy and were treated with aprepitant, dexamethasone, granisetron, and ramosetron or palonosetron. The patients were divided into two groups: patients given granisetron and ramosetron (the first-generation group), and those given palonosetron (palonosetron group). The percentage of patients with a complete response or total control was assessed. They were divided into three phases: 0-216 h (overall phase), 0-120 h (remedial phase), and 120-216 h (after phase). The remedial phase was further divided into 0-24 h (early phase) and 24-120 h (later phase). Moreover, the nutritional status of each patient was assessed by noting the patients' total calorie-intake per day and total parenteral nutrition. First-generation 5-HT3 RAs and palonosetron were used for treatment in 18 and 28 patients, respectively. The complete response rate and caloric oral intake of the later phase were higher in the palonosetron group than in the first-generation group. We conclude that palonosetron treatment was more effective than first-generation 5-HT3 RAs in controlling multiple-day chemotherapy-induced nausea and vomiting.

EGFR in enterocytes & endothelium and HIF1α in enterocytes are dispensable for massive small bowel resection induced angiogenesis.

BACKGROUND: Short bowel syndrome (SBS) results from significant loss of small intestinal length. In response to this loss, adaptation occurs, with Epidermal Growth Factor Receptor (EGFR) being a key driver. Besides enhanced enterocyte proliferation, we have revealed that adaptation is associated with angiogenesis. Further, we have found that small bowel resection (SBR) is associated with diminished oxygen delivery and elevated levels of hypoxia-inducible factor 1-alpha (HIF1α). METHODS: We ablated EGFR in the epithelium and endothelium as well as HIF1α in the epithelium, ostensibly the most hypoxic element. Using these mice, we determined the effects of these genetic manipulations on intestinal blood flow after SBR using photoacoustic microscopy (PAM), intestinal adaptation and angiogenic responses. Then, given that endothelial cells require a stromal support cell for efficient vascularization, we ablated EGFR expression in intestinal subepithelial myofibroblasts (ISEMFs) to determine its effects on angiogenesis in a microfluidic model of human small intestine. RESULTS: Despite immediate increased demand in oxygen extraction fraction measured by PAM in all mouse lines, were no differences in enterocyte and endothelial cell EGFR knockouts or enterocyte HIF1α knockouts by POD3. Submucosal capillary density was also unchanged by POD7 in all mouse lines. Additionally, EGFR silencing in ISEMFs did not impact vascular network development in a microfluidic device of human small intestine. CONCLUSIONS: Overall, despite the importance of EGFR in facilitating intestinal adaptation after SBR, it had no impact on angiogenesis in three cell types-enterocytes, endothelial cells, and ISEMFs. Epithelial ablation of HIF1α also had no impact on angiogenesis in the setting of SBS.