Neurolymphomatosis diagnosed after a recurrence of facial palsy.

Neurolymphomatosis (NL) is a rare complication of non-Hodgkin's lymphoma, characterized by the infiltration of lymphoma cells into the peripheral nerves. A 54-year-old woman initially presented with right facial palsy without any other significant symptoms and was diagnosed with Bell's palsy. Despite initial improvement, her condition recurred, prompting further evaluation. Magnetic resonance imaging (MRI) revealed contrast enhancement from the tympanic segment to the surface of the masseter muscle along the right facial nerve and an adjacent mass lesion. Biopsy of the mass revealed a diagnosis of T-cell/histiocyte-rich large B-cell lymphoma. Chemotherapy resulted in complete resolution of facial palsy. Follow-up MRI confirmed the absence of contrast enhancement along the facial nerve. Facial palsy was considered to be caused by NL. This case was classified as that of primary NL because the facial palsy was the first manifestation of a hematologic malignancy. Recurrent facial palsy, which is atypical in Bell's palsy, led to further evaluation with MRI, which finally resulted in the diagnosis of malignant lymphoma. In cases of recurrent facial palsy, clinicians should consider various diagnoses, including that of NL, and advocate early imaging tests and biopsy, if possible, for accurate diagnosis and improved outcomes.

Diffuse large B-cell lymphoma with DNA copy number changes in a Japanese black calf.

A 2-month-old Japanese Black calf exhibited mandibular and superficial cervical lymph node swelling. Fine needle aspiration cytology of the superficial cervical lymph node revealed large lymphoblast-like cells with mitoses. Hematological examination revealed remarkable lymphocytosis with atypical lymphocytes. Increased activities of serum total lactate dehydrogenase and thymidine kinase were detected. At necropsy, generalized swelling of lymph nodes was observed. Histopathological analysis revealed diffuse proliferation of medium-sized round centroblastic neoplastic cells that were positive for CD20, CD79α, PAX5, and BLA-36, and negative for CD3, CD5, CD10, and CD34. The calf was diagnosed with centroblastic diffuse large B-cell lymphoma (DLBCL) based on these findings. Analysis of DNA copy number variation revealed an increased copy number for the GIMAP family relative to that in healthy cattle. Moreover, decreases in copy numbers of GBP-1, MIR3141, OR5P1E, and PTPRG relative to those in healthy cattle were also observed. Because DNA copy number variation represent a major contribution to the somatic mutation landscapes in human tumors, these findings suggest that DNA copy number changes might have contributed to the onset of DLBCL in the present case.

Monoclonal proliferation of B-cells with two integration sites of bovine leukemia virus proviral DNA in cattle with enzootic bovine leukosis.

The present study analyzed B-cell clonality and bovine leukemia virus (BLV) provirus integration sites in cattle with enzootic bovine leukosis (EBL) having BLV proviral copy numbers less or greater than the number of bovine nucleated cells. EBL cattle with BLV copy numbers less than the number of bovine nucleated cells showed monoclonal and biclonal proliferation of B-cells with one BLV provirus integration site. On the other hand, EBL cattle with BLV copy numbers greater than the number of bovine nucleated cells showed monoclonal proliferation of B-cells with two BLV provirus integration sites. These results suggest that superinfection of BLV can occur in EBL cattle.

Real-world progression-free survival and overall survival of palbociclib plus endocrine therapy (ET) in Japanese patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer in the first-line or second-line setting: an observational study.

BACKGROUND: A recent large real-world study conducted in the United States reported the effectiveness of palbociclib plus aromatase inhibitor in HR+/HER2- advanced breast cancer (ABC). However, local clinical practice and available medical treatment can vary between Japan and Western countries. Thus, it is important to investigate Japanese real-world data. This observational, multicenter study (NCT05399329) reports the interim analysis of effectiveness of palbociclib plus ET as first-line or second-line treatment for HR+/HER2- ABC by estimating real-world progression-free survival (rwPFS) and overall survival (OS) in Japanese routine clinical practice. METHODS: Real-world clinical outcomes and treatment patterns of palbociclib plus ET were captured using a medical record review of patients diagnosed with HR+/HER2- ABC who had received palbociclib plus ET in the first-line or second-line treatment across 20 sites in Japan. The primary endpoint was rwPFS; secondary endpoints were OS, real-world overall response rate, real-world clinical benefit rate, and chemotherapy-free survival. RESULTS: Of the 677 eligible patients, 420 and 257 patients, respectively, had received palbociclib with ET as first-line and second-line treatments. Median rwPFS (95% confidence interval) was 24.5 months (19.9-29.4) for first-line and 14.5 months (10.2-19.0) for second-line treatment groups. Median OS was not reached in the first-line group and was 46.7 months (38.8-not estimated) for the second-line group. The 36-month OS rates for de novo metastasis, treatment-free interval (TFI) ≥ 12 months, and TFI < 12 months were 80.2% (69.1-87.7), 82.0% (70.7-89.3), and 66.0% (57.9-72.9), respectively. CONCLUSION: The addition of palbociclib to ET was effective for treating HR+/HER2- ABC in Japanese routine clinical practice.

Non-suppurative and necrotizing testicular arteritis in the male reproductive organs of a heavy draft horse.

Equine testicular arteritis commonly occurs as a consequence of the migration of nematode larvae or equine arteritis virus (EAV) infection. However, testicular arteritis without evidence of these infections has been reported, and the underlying pathogenesis remains unclear. We encountered testicular arteritis without evidence of nematode or EAV infection in a 3-year-old male heavy draft horse with scrotal enlargement. Grossly, the volume of the pampiniform plexus was markedly increased due to edema. Histologically, non-suppurative and necrotizing testicular arteritis, characterized by lymphocyte infiltration and fibrinoid necrosis of the arterial walls, was diffusely observed in the spermatic cord, pampiniform plexus (most severe), testis, and epididymis. We were unable to identify the cause of arteritis, such as a viral infection or autoimmune abnormality.

Scintillation properties of lithium-6 salicylate-loaded liquid scintillators.

The limited availability of conventional 3He proportional counters provides impetus for developing novel neutron detectors. As a candidate, lithium-6-loaded liquid scintillators with neutron/gamma pulse shape discrimination (n-γ PSD) capabilities have been developed. However, the trade-off relationship between the 6Li-loading amount and scintillation light yield is a significant problem. This is because 6Li-loading involves the addition of non-luminescent materials, which cause non-radiative relaxation of the excited states. Therefore, aiming to reduce non-radiative relaxation, we chose lithium-6 salicylate (6LiSal), which shows fluorescence in the visible light region, as a chemical for 6Li-loading. In this study, we analyzed the photoluminescence/scintillation properties based on the Förster resonance energy transfer and investigated the optimal content for obtaining a high light yield. By maximizing the sequential energy transfer from the solvent (toluene) to the phosphor (POPOP), a high light yield 6Li-loaded liquid scintillator (4220 photons per MeV under gamma-ray irradiation) with a 6Li concentration of approximately 0.1 wt% was developed. Thermal neutron events were successfully detected with a light yield of 3970 photons per neutron, which is more than three times higher than those of other organic scintillators. In addition, focusing on the triplet-triplet annihilation process and further optimizing the component for the n-γ PSD, the thermal neutron and gamma-ray events were successfully separated. The developed high light yield 6Li-loaded liquid scintillators show n-γ PSD capabilities and can be promising candidates as alternative detectors to the 3He proportional counter.

Prophylactic activity of orally administered dry-heat-sterilized Acremonium egyptiacum against Trypanosoma congolense-induced animal African trypanosomosis.

Animal African trypanosomosis (AAT) is an important global disease of livestock that causes economic losses of up to 4.5 billion US dollars per year. Thus, eliminating AAT in endemic countries will improve agricultural productivity and economic growth. To prevent AAT, vector control and the development of prophylactic drugs are crucial. Ascofuranone (AF) is a bioactive fungal compound with proven in vitro trypanocidal potency and in vivo treatment efficacy. However, the complex stereoselective synthesis of AF has prevented its cost-effective industrial production. Recently, a genetically modified strain of Acremonium egyptiacum fungus that produces a high yield of AF was developed. Therefore, we hypothesized that the oral administration of the AF-producing fungus itself may be effective against AAT. Hence, this study aimed to evaluate the prophylactic activity of orally administered dry-heat-sterilized A. egyptiacum against Trypanosoma congolense IL3000 infection using a mouse model. The survival rate was significantly prolonged (p = 0.009), and parasitemia was suppressed in all AF-fungus-treated groups (Group 1-9) compared with that in the untreated control group (Group 10). Hence, the trypanocidal activity of AF was retained after dry-heat-sterilization of the AF-producing fungus and that its oral administration effectively prevented AAT. Since AAT is endemic to rural areas with underdeveloped veterinary infrastructure, dry-heat-sterilized A. egyptiacum would be the most cost-effective potential treatment for AAT.

Transplantation of Human Embryonic Stem Cell-Derived Pericyte-Like Cells Transduced with Basic Fibroblast Growth Factor Promotes Angiogenic Recovery in Mice with Severe Chronic Hindlimb Ischemia.

Critical limb ischemia (CLI) is a state of severe peripheral artery disease, with no effective treatment. Cell therapy has been investigated as a therapeutic tool for CLI, and pericytes are promising therapeutic candidates based on their angiogenic properties. We firstly generated highly proliferative and immunosuppressive pericyte-like cells from embryonic stem (ES) cells. In order to enhance the angiogenic potential, we transduced the basic fibroblast growth factor (bFGF) gene into the pericyte-like cells and found a significant enhancement of angiogenesis in a Matrigel plug assay. Furthermore, we evaluated the bFGF-expressing pericyte-like cells in the previously established chronic hindlimb ischemia model in which bone marrow-derived MSCs were not effective. As a result, bFGF-expressing pericyte-like cells significantly improved blood flow in both laser Doppler perfusion imaging (LDPI) and dynamic contrast-enhanced MRI (DCE-MRI). These findings suggest that bFGF-expressing pericyte-like cells differentiated from ES cells may be a therapeutic candidate for CLI.

Histologic, immunohistochemical, and in situ hybridization study of myxoid stroma in feline oral squamous cell carcinoma.

Oral squamous cell carcinoma (oSCC) is a highly invasive malignant neoplasm in cats. Recently, tumor stroma, known as tumor microenvironments, have been considered to play an essential role in tumor progression. However, their role in feline squamous cell carcinoma (SCC) remains unclear. This study aimed to reveal the cancer microenvironment of feline oSCC and evaluate the pathological mechanisms of progression. We used 19 samples from 17 cats with oSCC, which were examined using light microscopy, immunohistochemistry, and in situ hybridization (RNAscope®). Feline oSCCs had two types of stroma, namely fibrotic and myxoid stromal reaction patterns, which were easily distinguished using hematoxylin-eosin staining. The myxoid stroma was rich in hyaluronic acid, which seems to be produced by neoplastic cells. Furthermore, the presence of myxoid stroma was correlated with histological parameters, including the appearance of cancer-associated fibroblasts and tumor budding. Periostin protein expression was also frequently observed in the stroma of feline oSCC and was significantly more common in the myxoid stromal reaction pattern group than in the fibrotic group. Positive signals for periostin mRNA were detected in stromal cancer-associated fibroblasts. This study indicates that the interaction between neoplastic cells and stromal reaction pattern components, such as hyaluronic acid and periostin, may be involved in tumor malignancy. Therefore, we propose that focus be placed not only on the tumor tissue but also on the characterization of the stroma for analyzing feline oSCC.

Expression profile analysis of the transient receptor potential (TRPM) channel, a possible target of praziquantel in Schistosoma japonicum.

The WHO considers schistosomiasis, which is controlled by the mass administration of the drug praziquantel (PZQ), to be a neglected tropical disease. Despite its clinical use for over four decades, PZQ remains the only choice of chemotherapy against this disease. Regarding the previous studies that demonstrated that PZQ activates the transient receptor potential (TRP) channel in Schistosoma mansoni (Sm.TRPMPZQ), the expression profile of the ortholog of this channel gene (Smp_246790.5) in S. japonicum (EWB00_008853) (Sj.TRPMPZQ) was analyzed. The relative expression of this gene in various stages of the parasite lifecycle was analyzed by quantitative real-time reverse transcription-PCR (qRT-PCR), and the expression of Sj.TRPMPZQ was observed by immunohistochemical staining using anti-serum against the recombinant Sj.TRPMPZQ protein. qRT-PCR revealed the significantly lower mRNA expression in the snail stage in comparison to other stages (p < 0.01). The relative quantity of the Sj.TRPMPZQ expression for paired females, unpaired males, and eggs was 60%, 56%, and 68%, respectively, in comparison to paired males that showed the highest expression (p < 0.05). Interestingly, immunostaining demonstrated that Sj.TRPMPZQ is expressed in the parenchyma which contains muscle cells, neuronal cells and tegument cells in adult worms. This may support the two major effects of PZQ-worm paralysis and tegument disruption-induced by channel activation. Moreover, the channel was expressed in both the eggshell and the miracidia inside, but could not be observed in sporocyst. These results suggest that the expression of Sj.TRPMPQZ corresponds to the known sensitivity of S. japonicum to PZQ.

Changes in cell-free DNA after short-term palbociclib and fulvestrant treatment for advanced or metastatic hormone receptor-positive and human epidermal growth factor 2-negative breast cancer.

PURPOSE: Here, we investigated the potential predictive and elucidating efficacy of cell-free DNA (cfDNA) changes on clinical outcomes and biological effects, respectively, after short-term palbociclib and fulvestrant treatment for patients with hormone receptor (HR)-positive and human epidermal growth factor 2 (HER2)-negative advanced or metastatic breast cancer (ABC). METHODS: In this secondary analysis of the Japan Breast Cancer Research Group-M07 (FUTURE) trial, blood cfDNA was obtained before palbociclib treatment and on day 15 of cycle one (28-day cycle). Target enrichment was performed using next-generation sequencing; progression-free survival (PFS) was compared based on cfDNA changes between baseline and day 15 of cycle one after combination therapy. RESULTS: Fifty-six patients (112 paired blood samples) were examined. The median follow-up time was 8.9 months. PIK3CA (30.4%, 17/56), FOXA1 (30.4%, 17/56), and ESR1 (28.6%, 16/56) were most frequently mutated at baseline. The number of mutated genes was significantly decreased on day 15 compared with that at baseline (paired t test: P value = 0.025). No significant difference was observed in PFS (decrease group, 7.9 m vs the others, 9.3 m; log-rank P value = 0.75; hazard ratio, 1.13; 95% confidence interval, 0.53-2.41). Among patients without previous aromatase inhibitor treatment (n = 15), three (20%) had ESR1 mutations after progression to fulvestrant. CONCLUSION: No significant association was observed between changes in mutated genes after short-term palbociclib and fulvestrant treatment and disease progression; a significant reduction in cfDNA mutation level was observed on day 15 of cycle one. Clinical meanings of cfDNA should be investigated in the future trials.

Risk Factors for Eribulin-induced Severe Neutropenia in Patients With Recurrent Breast Cancer.

BACKGROUND/AIM: Eribulin is an effective chemotherapeutic agent for advanced and metastatic breast cancer. However, severe neutropenia occurs in 30-40% of patients and interferes with the recommended treatment schedule. Neutropenia is a major cause of treatment interruptions, delays, or even relative dose reductions. This study aimed to examine the risk factors for severe neutropenia after eribulin treatment. PATIENTS AND METHODS: We retrospectively evaluated 263 patients with metastatic breast cancer who had received eribulin therapy. Risk factors for severe neutropenia in the first cycle were evaluated. RESULTS: Severe neutropenia in cycle 1 occurred in 50% of the patients. Multivariate analysis suggested six risk factors for severe neutropenia: low baseline neutrophil count and body mass index, high aspartate aminotransferase and bilirubin levels, creatinine clearance (CrCl) less than 50 ml/min, and eribulin dose of 1.4 mg/m2 Conclusion: This is one of the few studies to simultaneously examine both hepatic and renal functions in relation to severe neutropenia induced by eribulin. We have provided important information to support the close monitoring of patients with these risk factors and subsequent dosage adjustments, if necessary.

Patients Offer Radiofrequency Ablation Therapy for Early Breast Cancer as Local Therapy (PO-RAFAELO) Study under the Patient-proposed Health Services.

Introduction: Due to the increase in the number of early-stage breast cancer patients, there is growing interest in minimally invasive local therapies for breast cancer. Radiofrequency ablation (RFA) therapy is one of the most promising minimally invasive treatments. The Radiofrequency Ablation Therapy for Early Breast Cancer as Local Therapy (RAFAELO) study, a multicenter collaborative study that aims to validate the efficacy and safety of RFA and to standardize its use for early-stage breast cancer, was conducted under the Advanced Medical Care B system in 2013. This study enrolled the expected number of patients in November 2017; moreover, it is currently in the follow-up period. Some patients with early-stage breast cancer who are eligible for RFA could not receive the RFA treatment, as it is still not covered by insurance. Therefore, the Patients Offer Radiofrequency Ablation Therapy for Early Breast Cancer as Local Therapy (PO-RAFAELO) study under the Patient-proposed Health Services (PPHS) was proposed and approved in March 2019. Methods: The PPHS is a system that allows patients to receive prompt access to advanced medical care at a medical facility close to them, starting with their request. This system is considered a part of the specific and special medical coverage. The PO-RAFAELO study is the only study in the surgical field utilizing the PPHS, aiming to help in achieving regulatory approval and insurance coverage of RFA for breast cancer. Results: As of January 2023, 120 patients have undergone RFA using the PPHS and no grade 3 or higher early adverse events have occurred. Conclusions: A certain number of patients with early-stage breast cancer prefer nonsurgical treatment, and it is important to provide information regarding the availability of RFA for early-stage breast cancer under the PPHS.Trial registration: registered with Japan Registry of Clinical Trial on March 06, 2019 (Trial ID: jRCTs032180187).

LINE-1 Methylation Status in Canine Splenic Hemangiosarcoma Tissue and Cell-Free DNA.

Splenic hemangiosarcoma is one of the most common malignant tumors in dogs, and early diagnosis is of great importance for achieving a good prognosis. DNA methylation plays an important role in cancer development. Long interspersed nuclear element 1 (LINE-1) is the most abundant repetitive element in the genome. LINE-1 hypomethylation has been shown to be related to carcinogenesis in humans, and it has been used as a novel cancer biomarker. This study aimed to evaluate the methylation status of LINE-1 in tumor tissue and circulating cell-free DNA and assess its clinical significance in canine splenic hemangiosarcoma. Genomic DNA was isolated from splenic masses of 13 dogs with hemangiosarcoma, 11 with other malignant tumors, and 15 with benign lesions. LINE-1 methylation was quantified using methylation-sensitive and -insensitive restriction enzyme digestion followed by real-time polymerase chain reaction. Additionally, blood samples were collected from eight patients to isolate cell-free DNA to determine LINE-1 methylation status changes during the treatment course. LINE-1 methylation in tumor samples was significantly lower in patients with hemangiosarcoma than in those with other malignant tumors and benign lesions. Non-significant but similar results were observed for the cell-free DNA samples. Our results demonstrate that LINE-1 methylation status is a potential biomarker for splenic hemangiosarcoma.

Real-World Predictors of Severe Neutropenia Associated with Palbociclib and Endocrine Therapy for Metastatic Breast Cancer in Japanese Patients.

Therapy for patients of metastatic breast cancer based on palbociclib, a cyclin-dependent kinase 4/6 inhibitor, has been approved in Japan. However, the risk factors for palbociclib-induced severe neutropenia in Japanese patients are rarely reported. Hence, the present study is aimed to identify the risk factors for adverse events requiring palbociclib dose reduction or discontinuation, and to identify the factors necessary to identify a more stable strategy for treatment continuation. This retrospective cohort analysis included patients with advanced breast cancer treated with 125 mg/d palbociclib. We demonstrated that severe neutropenia required significant dose reduction or therapy cessation. Most (77%) of the patients had severe neutropenia within the three courses. Risk factors for grade 3 or higher included low neutrophil counts (< 3250 /µL) before treatment [odds ratio (OR) = 9.10, 95% confidence interval (CI) (2.80-29.41), p < 0.001] and high age-adjusted Charlson comorbidity index (> 9) [OR = 1.64, 95% CI (1.09-2.48), p = 0.018]. Thus, low baseline neutrophil counts and high values for Age-adjusted Charlson comorbidity index are prospective predictive markers for palbociclib-induced severe neutropenia.

Long-term voice evaluation after arytenoid adduction surgery in patients with unilateral vocal fold paralysis.

PURPOSE: Laryngeal framework surgery, including medialization laryngoplasty and arytenoid adduction (AA), is expected to have a lasting or permanent effect in patients with unilateral vocal fold paralysis (UVFP); however, there are few reports about the long-term outcomes of AA. This study aimed to evaluate the long-term postoperative effects of AA surgery and examine its stability and reliability. METHODS: This study collected the voice handicap index (VHI) questionnaire from patients with UVFP who underwent AA more than 2 years previously. The VHI values preoperatively and 3 months postoperatively (early postoperative evaluation) were retrospectively calculated, and VHI values more than 2 years after surgery (late postoperative evaluation) were collected by mailing a sheet to the patients and asking to fill and return it. Possible influenced subscales such as age, sex, causes of UVFP, affected side, and surgeons were also analyzed. RESULTS: A total of 77 patients with UVFP who underwent AA had significantly lower early and late postoperative evaluations than preoperative evaluations. In 38 patients with no missing values, there were no significant differences between early and late postoperative evaluations, measured at a median of approximately 5 years. There were also no significant differences between early and late postoperative evaluations in any of the subscale groups. CONCLUSION: Patients with UVFP who underwent AA surgery achieved stable voice improvement in the long term after surgery.

Tips and Complications of Two-step Open Procedure for Ethanol Sclerosis Therapy for a Venous Hemangioma of the Thoracic Spine: A Case Report.

Introduction: Venous hemangiomas of the thoracic spine are rare tumors that are diagnose based on radiological findings. Ethanol sclerosis therapy through the percutaneous or open approaches has been reported to be useful treatment options. Therefore, radiological examination and the treatment procedure can be performed together. As pathological diagnosis of the tumor is important, a strategy that comprises biopsy followed by definitive treatment is ideal. The tips and complications of the two-step open procedure for ethanol sclerosis therapy have not been discussed in detail. This is the first report of this kind in the literature, especially about the tips and complications. Case Report: A 51-year-old woman presented with pain in the upper part of her back. Radiological examination revealed a hypervascular tumor at the second thoracic vertebra. We first performed an open biopsy along with decompression and fixation surgery, because the patient developed a walking disability with motor weakness in her right leg. The tumor was pathologically diagnosed as a venous hemangioma. Therefore, we performed ethanol sclerosis therapy using the open approach as a curative technique for the tumor 17 days after the initial surgery. A total of 10 mL of a mixture of 100% ethanol and a lipid-soluble contrast medium - which improve visibility - was injected intermittently and slowly. This was followed by the injection of 3 mL of a water-soluble contrast medium to confirm sclerosis. Immediately after the last procedure, the amplitudes of motor-evoked potentials in all bilateral lower extremity muscles disappeared simultaneously. The patient incomplete paralysis of the lower extremity and transient dysuria postoperatively; however, she could walk without assistance after 5 months. Conclusion: This case highlights the following: First, the two-step procedure of open biopsy followed by ethanol injection using the open approach allowed accurate diagnosis and effective treatment. Second, additional injection of a water-soluble contrast medium to confirm sclerosis after ethanol injection can cause paralysis. Third, a mixture of ethanol and a lipid-soluble contrast medium effective improves visibility to identify expansions. These experiences will be useful for following ethanol sclerosis therapy for a venous hemangioma of the thoracic spine.

Efficacy of oral administration of ascofuranone with and without glycerol against Trypanosoma congolense.

In many developing countries, trypanosomosis in animals results in the reduction of livestock productivity. Since trypanosomosis is endemic to rural areas where medical and veterinary infrastructure is underdeveloped, development of affordable and easy-to-maintain drugs for treatment and prophylaxis against trypanosomosis is necessary. To this end, in this study, we evaluated the efficacy of oral administration of ascofuranone (AF), with and without glycerol (GOL), against trypanosomosis, using a mouse model. We used T. congolense IL3000, the most virulent animal-infecting trypanosome, and BALB/c mice in this study. Eight mice were assigned to either of Groups 1-7: non-infected, untreated, AF 10, 20, 30, 50, and 100 mg/kg with or without GOL, respectively. In the experiment with AF administered with GOL, survival rates were 0% in Group 2 (untreated) and Group 3 (AF 10 mg/kg), 37.5% in Group 4 (AF 20 mg/kg) and Group 5 (AF 30 mg/kg), 50% in Group 6 (AF 50 mg/kg), and 100% in Group 7 (AF 100 mg/kg). In groups in which AF was administered without GOL, survival rates were 0% in Group 2 (untreated), Group 3 (AF 10 mg/kg), Group 4 (AF 20 mg/kg), Group 5 (AF 30 mg/kg), and Group 6 (AF 50 mg/kg), and 12.5% in Group 7 (AF 100 mg/kg), with one mouse surviving till the end of the observation period. The results of the analysis showed that survival rates were significantly higher in all groups (Groups 3-7) than in the untreated group (Group 2) (p < 0.05). Furthermore, a comparison of groups with or without GOL at the same AF concentration revealed that the survival rate was significantly higher in the group treated with GOL. These results suggest that the treatment efficacy of AF against animal trypanosomosis caused by T. congolense is greater when co-administered with GOL, and that oral administration of AF could be a new therapeutic strategy for animal African trypanosomosis.

Clinical Management of Potential Toxicity of Abemaciclib and Approaches to Ensure Treatment Continuation.

INTRODUCTION: The association between abemaciclib dose reduction and treatment adherence is not clear. In this study, we examined real-world data of Japanese patients with advanced breast cancer (ABC) to determine how abemaciclib dose reduction is related to treatment continuation. METHODS: This retrospective observational study involved 120 consecutive patients with ABC who received abemaciclib from December 2018 to March 2021. The time to treatment failure (TTF) was estimated using the Kaplan-Meier method. Univariate and multivariate analyses were performed to identify factors associated with a TTF of >365 days (TTF365). RESULTS: According to the dose reduction during treatment, the patients were classified into 100, 200, and 300 mg/day abemaciclib groups. The 300 mg/day group had a TTF of 7.4 months, whereas the 100 and 200 mg/day groups had significantly longer TTFs (17.9 and 17.3 months, respectively; P = 0.0002). In this study, relative to the 300 mg/day arm, TTF was improved in 200mg/day arm and 100 mg/day arm (hazard ratio [HR], 0.55; 95% confidence interval [CI], 0.33-0.93) and [HR], 0.37; 95% CI, 0.19-0.74). For patients who received 300mg/day of abemaciclib dose arm, 200mg/day, and 100mg/day, the median TTF was 7.4 ,17.9 and 17.3 months. The frequently reported adverse effects (AEs) were anemia, increased blood creatinine levels, diarrhea, and neutropenia (90%, 83%, 83%, and 75% of the patients, respectively). Neutropenia, fatigue, and diarrhea were the top AEs causing dose reduction. A multivariate analysis that examined factors associated with achieving TTF 365 confirmed that dose down was an important factor (odds ratio: 3.95, 95% confidence interval: 1.68-9.36, P = 0.002). CONCLUSIONS: In this study, the 100 and 200 mg/day groups had a longer TTF than the 300 mg/day group, and dose reduction was identified as an important factor in achieving longer TTF.