A rat-based preclinical platform facilitating transcatheter hepatic arterial infusion in immunodeficient rats with liver xenografts of patient-derived pancreatic ductal adenocarcinoma.

Liver metastases from pancreatic ductal adenocarcinoma (PDAC) are highly fatal. A rat-based patient-derived tumor xenograft (PDX) model is available for transcatheter therapy. This study aimed to create an immunodeficient rat model with liver xenografts of patient-derived primary PDAC and evaluate efficacy of hepatic arterial infusion chemotherapy with cisplatin in this model. Three patient-derived PDACs were transplanted into the livers of 21 rats each (totally, 63 rats), randomly assigned into hepatic arterial infusion, systemic venous infusion, and control groups (n = 7 each) four weeks post-implantation. Computed tomography evaluated tumor volumes before and four weeks after treatment. Post-euthanasia, resected tumor specimens underwent histopathological examination. A liver-implanted PDAC PDX rat model was established in all 63 rats, with first CT identifying all tumors. Four weeks post-treatment, arterial infusion groups exhibited significantly smaller tumor volumes than controls for all three tumors on second CT. Xenograft tumors histologically maintained adenocarcinoma features compared to original patient tumors. Ki67 expression was significantly lower in arterial infusion groups than in the other two for the three tumors, indicating reduced tumor growth in PDX rats. A liver-implanted PDAC PDX rat model was established as a rat-based preclinical platform. Arterial cisplatin infusion chemotherapy represents a potential therapy for PDAC liver metastasis.

Reduction of adverse reactions and correlation between post-vaccination fever and specific antibody response across successive SARS-CoV-2 mRNA vaccinations.

Background: SARS-CoV-2 mRNA vaccination, recognized for high immunogenicity, frequently induces adverse reactions, especially fever. We previously reported a correlation between post-vaccination fever and specific antibody responses to the primary series and first booster. We herein report changes in adverse reactions and the correlation between post-vaccination fever and antibody responses across successive vaccinations, from monovalent to bivalent mRNA vaccines. Methods: This cohort study was conducted at a Japanese hospital to investigate adverse reactions to the monovalent primary, first booster, and BA.4/5 bivalent BNT162b2 vaccinations. Local and systemic reactions were reported through a self-reporting diary after each dose. The spike-specific IgG titers were measured following each vaccination. Results: Across 727 vaccinations in the vaccine series, the bivalent booster induced fewer adverse reactions than earlier doses. Fever ≥ 38.0 °C was significantly less frequent in the bivalent booster (12.3 %) compared to the primary series and monovalent booster (22.0 %, 26.2 %, p < 0.001). Reaction severity was also reduced in the bivalent booster. In the analysis of 70 participants with complete data for all doses, post-vaccination fever ≥ 38.0 °C exhibited the highest relative risk (RR) among all solicited reactions throughout the vaccine series (RR: 5.24 [95 % CI: 2.40-11.42] for monovalent and 6.24 [95 % CI: 2.14-18.15] for bivalent). The frequency of fever ≥ 38.0 °C after all doses was 8.6 % (6/70), with no fever ≥ 39.0 °C across all vaccinations. A high-grade post-vaccination fever was correlated with higher IgG titers, with multivariate analyses confirming this correlation as independent for each dose and unaffected by previous post-vaccination fever. Conclusions: The bivalent mRNA vaccine booster showed fewer and milder adverse reactions than the monovalent doses. Although vaccinees with a history of post-vaccination fever were more likely to experience fever after a subsequent dose, such recurrences were infrequent. A correlation between post-vaccination fever and increased IgG titers was identified for each vaccination, irrespective of post-vaccination fever history.

Text and image generation from intracranial electroencephalography using an embedding space for text and images.

OBJECTIVE: Invasive brain-computer interfaces (BCIs) are promising communication devices for severely paralyzed patients. Recent advances in intracranial electroencephalography (iEEG) coupled with natural language processing have enhanced communication speed and accuracy. It should be noted that such a speech BCI uses signals from the motor cortex. However, BCIs based on motor cortical activities may experience signal deterioration in users with motor cortical degenerative diseases such as amyotrophic lateral sclerosis (ALS). An alternative approach to using iEEG of the motor cortex is necessary to support patients with such conditions. Approach: In this study, a multimodal embedding of text and images was used to decode visual semantic information from iEEG signals of the visual cortex to generate text and images. We used contrastive language-image pretraining (CLIP) embedding to represent images presented to 17 patients implanted with electrodes in the occipital and temporal cortexes. A CLIP image vector was inferred from the high-γ power of the iEEG signals recorded while viewing the images. Main results: Text was generated by CLIPCAP from the inferred CLIP vector with better-than-chance accuracy. Then, an image was created from the generated text using StableDiffusion with significant accuracy. Significance: The text and images generated from iEEG through the CLIP embedding vector can be used for improved communication. .

Atypical heat shock transcription factor HSF5 is critical for male meiotic prophase under non-stress conditions.

Meiotic prophase progression is differently regulated in males and females. In males, pachytene transition during meiotic prophase is accompanied by robust alteration in gene expression. However, how gene expression is regulated differently to ensure meiotic prophase completion in males remains elusive. Herein, we identify HSF5 as a male germ cell-specific heat shock transcription factor (HSF) for meiotic prophase progression. Genetic analyzes and single-cell RNA-sequencing demonstrate that HSF5 is essential for progression beyond the pachytene stage under non-stress conditions rather than heat stress. Chromatin binding analysis in vivo and DNA-binding assays in vitro suggest that HSF5 binds to promoters in a subset of genes associated with chromatin organization. HSF5 recognizes a DNA motif different from typical heat shock elements recognized by other canonical HSFs. This study suggests that HSF5 is an atypical HSF that is required for the gene expression program for pachytene transition during meiotic prophase in males.

Virological and clinical outcomes in outpatients treated with baloxavir or neuraminidase inhibitors for A(H3N2) influenza: A multicenter study of the 2022-2023 season.

While clinical trials have illuminated both the virological and clinical efficacy of baloxavir for influenza and post-treatment viral resistance, these aspects warrant further study in real-world settings. In response, we executed a prospective, observational study of the Japanese 2022-2023 influenza season. A cohort of 73 A(H3N2)-diagnosed outpatients-36 treated with baloxavir, 20 with oseltamivir, and 17 with other neuraminidase inhibitors (NAIs)-were analyzed. Viral samples were collected before and after administering an antiviral on days 1, 5, and 10, respectively. Cultured viruses were amplified using RT-PCR and sequenced to detect mutations. Fever and other symptoms were tracked via self-reporting diaries. In the baloxavir cohort, viral detection was 11.1% (4/36) and 0% (0/36) on day 5 and day 10, respectively. Two isolates from day 5 (5.6%, 2/36) manifested I38T/M-substitutions in the polymerase acidic protein (PA). For oseltamivir and other NAIs, viral detection rates were 60.0% (12/20) and 52.9% (9/17) on day 5, and 16.7% (3/18) and 6.3% (1/16) on day 10, respectively. No oseltamivir-resistant neuraminidase mutations were identified after treatment. Median fever durations for the baloxavir, oseltamivir, and other NAI cohorts were 27.0, 38.0, and 36.0 h, respectively, with no significant difference. Two patients harboring PA I38T/M-substitutions did not exhibit prolonged fever or other symptoms. These findings affirm baloxavir's virological and clinical effectiveness against A(H3N2) in the 2022-2023 season and suggest limited clinical influence of post-treatment resistance emergence.

Impact of Tumor Subclassifications for Identifying an Appropriate Surgical Strategy in Patients with Intrahepatic Cholangiocarcinoma.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is subclassified into small and large duct types. The impact of these subclassifications for identifying appropriate surgical strategies remains unclear. PATIENTS AND METHODS: This study included 118 patients with ICC who underwent liver resection. Based on the pathological examination results, the participants were divided into the small duct-type ICC group (n = 64) and large duct-type ICC group (n = 54). The clinicopathological features and postoperative outcomes were compared between the two groups to investigate the impact of subclassification for selecting appropriate surgical strategies. RESULTS: Ten patients in the small duct-type ICC group had synchronous or metachronous hepatocellular carcinoma. The large duct-type ICC group had higher proportions of patients who underwent major hepatectomy, extrahepatic bile duct resection, portal vein resection, and lymph node sampling or dissection than the small duct-type ICC group. The large duct-type ICC group had significantly higher incidences of lymph node metastasis/recurrence and pathological major vessel invasion than the other. The small duct-type ICC group exhibited significantly higher recurrence-free and overall survival rates than the large duct-type ICC group. Further, the large duct-type ICC group had a significantly higher incidence of lymph node metastasis/recurrence than the small duct-type ICC at the perihilar region group. CONCLUSIONS: Suitable surgical strategies may differ between the small and large duct-type ICCs. In patients with large duct-type ICCs, hepatectomy with lymph node dissection and/or biliary reconstruction should be considered, whereas hepatectomy without these advanced procedures can be suggested for patients with small duct-type ICCs.

In vitro neuraminidase inhibitory concentrations (IC50) of four neuraminidase inhibitors in the Japanese 2022-23 season: Comparison with the 2010-11 to 2019-20 seasons.

To assess the extent of susceptibility to the four neuraminidase inhibitors (NAIs) approved in Japan of the epidemic viruses in the 2022-23 influenza season in Japan, we measured the 50 % inhibitory concentration (IC50) of oseltamivir, zanamivir, peramivir, and laninamivir in influenza virus isolates from patients. Viral isolation was done with specimens obtained prior to and after treatment, and the type/subtype was determined by RT-PCR using type- and subtype-specific primers. The IC50 was determined by a neuraminidase inhibition assay using a fluorescent substrate. Virus isolates, one A(H1N1)pdm09 and 74 A(H3N2), were measured in the 2022-23 season. The geometric mean IC50s of the 74 A(H3N2) isolated prior to treatment were 0.78 nM, 0.66 nM, 2.08 nM, and 2.85 nM for oseltamivir, peramivir, zanamivir, and laninamivir, respectively, comparable to those of the previous ten studied seasons. No A(H3N2) with highly reduced sensitivity to any of the NAIs was found in the 2022-23 season prior to or after drug administration. These results indicate that the sensitivity to these four commonly used NAIs has been maintained, at least for A(H3N2), in the 2022-23 influenza season in Japan, after the 2020-21 and 2021-22 seasons when the prevalence of influenza was extremely low.

An ecological transcriptome approach to capture the molecular and physiological mechanisms of mass flowering in Shorea curtisii.

Climatic factors have commonly been attributed as the trigger of general flowering, a unique community-level mass flowering phenomenon involving most dipterocarp species that forms the foundation of Southeast Asian tropical rainforests. This intriguing flowering event is often succeeded by mast fruiting, which provides a temporary yet substantial burst of food resources for animals, particularly frugivores. However, the physiological mechanism that triggers general flowering, particularly in dipterocarp species, is not well understood largely due to its irregular and unpredictable occurrences in the tall and dense forests. To shed light on this mechanism, we employed ecological transcriptomic analyses on an RNA-seq dataset of a general flowering species, Shorea curtisii (Dipterocarpaceae), sequenced from leaves and buds collected at multiple vegetative and flowering phenological stages. We assembled 64,219 unigenes from the transcriptome of which 1,730 and 3,559 were differentially expressed in the leaf and the bud, respectively. Differentially expressed unigene clusters were found to be enriched with homologs of Arabidopsis thaliana genes associated with response to biotic and abiotic stresses, nutrient level, and hormonal treatments. When combined with rainfall data, our transcriptome data reveals that the trees were responding to a brief period of drought prior to the elevated expression of key floral promoters and followed by differential expression of unigenes that indicates physiological changes associated with the transition from vegetative to reproductive stages. Our study is timely for a representative general flowering dipterocarp species that occurs in forests that are under the constant threat of deforestation and climate change as it pinpoints important climate sensitive and flowering-related homologs and offers a glimpse into the cascade of gene expression before and after the onset of floral initiation.

Comparing modeling methods of genomic prediction for growth traits of a tropical timber species, Shorea macrophylla.

Introduction: Shorea macrophylla is a commercially important tropical tree species grown for timber and oil. It is amenable to plantation forestry due to its fast initial growth. Genomic selection (GS) has been used in tree breeding studies to shorten long breeding cycles but has not previously been applied to S. macrophylla. Methods: To build genomic prediction models for GS, leaves and growth trait data were collected from a half-sib progeny population of S. macrophylla in Sari Bumi Kusuma forest concession, central Kalimantan, Indonesia. 18037 SNP markers were identified in two ddRAD-seq libraries. Genomic prediction models based on these SNPs were then generated for diameter at breast height and total height in the 7th year from planting (D7 and H7). Results and discussion: These traits were chosen because of their relatively high narrow-sense genomic heritability and because seven years was considered long enough to assess initial growth. Genomic prediction models were built using 6 methods and their derivatives with the full set of identified SNPs and subsets of 48, 96, and 192 SNPs selected based on the results of a genome-wide association study (GWAS). The GBLUP and RKHS methods gave the highest predictive ability for D7 and H7 with the sets of selected SNPs and showed that D7 has an additive genetic architecture while H7 has an epistatic genetic architecture. LightGBM and CNN1D also achieved high predictive abilities for D7 with 48 and 96 selected SNPs, and for H7 with 96 and 192 selected SNPs, showing that gradient boosting decision trees and deep learning can be useful in genomic prediction. Predictive abilities were higher in H7 when smaller number of SNP subsets selected by GWAS p-value was used, However, D7 showed the contrary tendency, which might have originated from the difference in genetic architecture between primary and secondary growth of the species. This study suggests that GS with GWAS-based SNP selection can be used in breeding for non-cultivated tree species to improve initial growth and reduce genotyping costs for next-generation seedlings.

Distinct features of SARS-CoV-2 humoral immunity against Omicron breakthrough infection.

BACKGROUND: SARS-CoV-2 Omicron breakthrough infection (Omicron-BTI) after vaccination has been frequently observed. A more detailed understanding of the humoral immunity against Omicron-BTI is required. METHODS: We measured strain-specific live-virus based neutralizing activity, anti-spike IgG, and anti-receptor-binding domain (RBD) IgG titers in individuals with Omicron/BA.1-BTI and directly compared them with controls with diverse combinations of wild-type (WT) mRNA vaccination and infection history. RESULTS: Omicron-BTI individuals showed markedly higher neutralizing titers against all the WT, Delta, and Omicron strains in convalescent sera, compared with unvaccinated Omicron-infection individuals with only Omicron neutralizing activity. Similar tendencies were found in strain-specific anti-spike and anti-RBD IgG titers. The Omicron-specificity (BA.1/WT neutralizing ratio), Omicron-neutralizing efficiency per antibody unit, and anti-Omicron RBD-directivity of anti-spike antibodies in Omicron-BTI individuals were all significantly lower than those in unvaccinated Omicron-infection individuals, but they were equivalent to or higher than those in uninfected vaccinees. The induction of Omicron-specific neutralizing activity after Omicron-BTI was not weakened for eight months from the last vaccination. CONCLUSIONS: These findings suggest that cross-reactive vaccine-induced immunity was intensively stimulated following Omicron breakthrough infection, which contributed to Omicron neutralization. Measuring SARS-CoV-2 variant-specific antibody levels as well as neutralizing activity is useful for evaluating humoral immunity after breakthrough infection in the current situation of antigenic gaps between vaccinated and epidemic (Omicron sub-lineages) strains.

Characteristics of Changes in Intrathecal Baclofen Dosage over Time due to Causative Disease.

Intrathecal baclofen (ITB) therapy effectively treats spasticity caused by brain or spinal cord lesions. However, only a few studies compare the course of treatment for different diseases. We investigated the change in daily dose of baclofen per year and its associated adverse events in patients presenting with the three most common etiologies at our institute: hereditary spastic paraplegia, cerebral palsy, and spinal cord injury. The ITB pumps were implanted from July 2007 to August 2019, with a mean follow-up period of 70 months. In patients with hereditary spastic paraplegia, baclofen dosage was reduced after eight years following ITB introduction, and the treatment was terminated in one patient owing to disease progression. In patients with cerebral palsy, the dosage increased gradually, and became constant in the 11th year. Patients with spinal cord injury gradually increased their baclofen dosage throughout the entire observation period. Severity and adverse event rates were higher in patients with cerebral palsy than in others. The degree and progression of spasticity varied depending on the causative disease. Understanding the characteristics and natural history of each disease is important when continuing ITB treatment.

Correlation between specific antibody response to wild-type BNT162b2 booster and the risk of breakthrough infection with omicron variants: Impact of household exposure in hospital healthcare workers.

BACKGROUND: The emergence of omicron variants exhibiting antigenic changes has led to an increase in breakthrough infection among individuals with a wild-type SARS-CoV-2 vaccine booster. The correlation between post-booster spike-specific antibodies and omicron infection risk remains unclear. METHODS: This prospective cohort study included SARS-CoV-2-naive healthcare workers with three-dose BNT162b2. Post-booster spike-specific IgG and interferon-γ levels were measured. Breakthrough infection was documented during a 10-month omicron-predominant period. Household and healthcare contacts were followed to identify subsequent infections. The IgG titers were additionally measured at the end of follow-up, and the titers at exposure were estimated from the two-point titers. RESULTS: Of 333 participants, 89 developed infection, of whom 37 (41.6 %) were household contacts. Kaplan-Meier curves indicated that higher IgG titers were significantly correlated with lower cumulative infection incidence (p = 0.029), whereas the interferon-γ levels were not (p = 0.926). Multivariate Cox analysis showed that increasing IgG titers were associated with a reduced hazard ratio (HR) of 0.26 (95% CI, 0.12-0.55). Household exposure posed a greater infection risk than healthcare exposure (HRs, 11.24 [6.88-18.40] vs. 2.82 [1.37-5.44]). The difference in geometric mean IgG titers of infected and uninfected participants was significant among household contacts (20,244 AU/mL vs. 13,842 AU/mL, p = 0.031). Estimation of IgG titers at exposure showed a significantly higher infection incidence in those exposed with titers of <3,000 AU/mL than in those with higher titers (79.2 % vs. 32.3 %, p < 0.001). CONCLUSIONS: Spike-specific antibodies induced by a wild-type SARS-CoV-2 vaccine booster are suggested to be effective in protecting against omicron infection. Household exposure would be a significant source of infection for hospital healthcare workers.

Utilization of three-dimensional fusion images with high-resolution computed tomography angiography for preoperative evaluation of microvascular decompression: patient series.

BACKGROUND: High-resolution computed tomography (CT), outfitted with a 0.25-mm detector, has superior capability for identifying microscopic anatomical structures compared to conventional CT. This study describes the use of high-resolution computed tomography angiography (CTA) for preoperative microvascular decompression (MVD) assessment and explores the potential effectiveness of three-dimensional (3D) image fusion with magnetic resonance imaging (MRI) by comparing it with traditional imaging methods. OBSERVATIONS: Four patients who had undergone preoperative high-resolution CTA and MRI for MVD at Osaka University Hospital between December 2020 and March 2022 were included in this study. The 3D-reconstructed images and intraoperative findings were compared. One patient underwent conventional CTA, thus allowing for a comparison between high-resolution and conventional CTA in terms of radiation exposure and vascular delineation. Preoperative simulations reflected the intraoperative findings for all cases; small vessel compression of the nerve was identified preoperatively in two cases. LESSONS: Compared with conventional CTA, high-resolution CTA showed superior vascular delineation with no significant change in radiation exposure. The use of high-resolution CTA with reconstructed 3D fusion images can help to simulate prior MVD. Knowing the location of the nerves and blood vessels can perioperatively guide neurosurgeons.

Transcriptomic responses of oil palm (Elaeis guineensis) stem to waterlogging at plantation in relation to precipitation seasonality.

Global warming-induced climate change causes significant agricultural problems by increasing the incidence of drought and flooding events. Waterlogging is an inevitable consequence of these changes but its effects on oil palms have received little attention and are poorly understood. Recent waterlogging studies have focused on oil palm seedlings, with particular emphasis on phenology. However, the transcriptomic waterlogging response of mature oil palms remains elusive in real environments. We therefore investigated transcriptomic changes over time in adult oil palms at plantations over a two-year period with pronounced seasonal variation in precipitation. A significant transcriptional waterlogging response was observed in the oil palm stem core but not in leaf samples when gene expression was correlated with cumulative precipitation over two-day periods. Pathways and processes upregulated or enriched in the stem core response included hypoxia, ethylene signaling, and carbon metabolism. Post-waterlogging recovery in oil palms was found to be associated with responses to heat stress and carotenoid biosynthesis. Nineteen transcription factors (TFs) potentially involved in the waterlogging response of mature oil palms were also identified. These data provide new insights into the transcriptomic responses of planted oil palms to waterlogging and offer valuable guidance on the sensitivity of oil palm plantations to future climate changes.

Achievement of sufficient antibody response after a fourth dose of wild-type SARS-CoV-2 mRNA vaccine in nursing home residents.

BACKGROUND: Infection control during COVID-19 outbreaks in nursing facilities is a critical public health issue. Antibody responses before and after the fourth (second booster) dose of wild-type severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine in nursing home residents have not been fully characterized. METHODS: This study included 112 individuals: 54 nursing home residents (mean age: 84.4 years; 35 SARS-CoV-2-naive and 19 previously infected) and 58 healthcare workers (mean age: 47.7 years; 25 SARS-CoV-2-naive and 33 previously infected). Antispike and antinucleocapsid antibody responses to messenger RNA vaccination were evaluated using serum samples collected shortly and 5 months after the third dose, and shortly after the fourth dose. RESULTS: The median immunoglobulin G (IgG) level in SARS-CoV-2-naive residents was similar to that in SARS-CoV-2-naive healthcare workers after the fourth dose (24,026.3 vs. 30,328.6 AU/mL, p = .79), whereas after the third dose the IgG level of SARS-CoV-2-naive residents was approximately twofold lower than that in SARS-CoV-2-naive healthcare workers. In residents with previous SARS-CoV-2 infection, timing of infection in relation to vaccination affected the kinetics of antibody responses. Residents infected after the third dose showed the highest IgG levels after the fourth dose among all groups (median: 64,328.8 AU/mL), in contrast to residents infected before initiating vaccination with antibody levels similar to those of SARS-CoV-2-naive residents. CONCLUSIONS: Advanced aged nursing home residents, poor responders in the initial SARS-CoV-2 vaccine series, could achieve sufficient antibody responses after the fourth (second booster) vaccination, comparable to those of younger adults.

SARS-CoV-2 strain-specific anti-spike IgG ELISA utilizing spike protein produced by silkworms.

BACKGROUND: A cost-effective and eco-friendly method is needed for the assessment of humoral immunity against SARS-CoV-2 in large populations. OBJECTIVE: We investigated the performance of an ELISA that uses silkworm-produced proteins to quantify the strain-specific anti-Spike IgG (anti-S IgG) titer. METHODS: The OD values for the anti-His-tag antibody, a standard material of ELISA quantification, were measured. Correlations between the ELISA for each strain and the Abbott SARS-CoV-2 IgG II Quant assay for the wild type were evaluated with serum samples from nine participants with various infection and vaccination statuses. RESULTS: Linear dose-responses were confirmed by high coefficients of determination: 0.994, 0.994, and 0.996 for the wild-type, Delta, and Omicron (BA.1) strain assays, respectively. The coefficient of determination for the wild-type and Delta strain assays was high at 0.959 and 0.892, respectively, while the Omicron strain assay had a relatively low value of 0.563. Booster vaccinees showed similar or higher titers against all strains compared to infected persons without vaccination. The Omicron-infected persons without vaccination had lower antibody titers against wild type than did the vaccinated persons. CONCLUSIONS: This study provides data indicating that the ELISA with silkworm-produced proteins makes it possible to discriminate and quantify the strain-specific anti-S IgG antibody induced by vaccination or infection.

Age-associated reduction of nuclear shape dynamics in excitatory neurons of the visual cortex.

Neurons decline in their functionality over time, and age-related neuronal alterations are associated with phenotypes of neurodegenerative diseases. In nonneural tissues, an infolded nuclear shape has been proposed as a hallmark of aged cells and neurons with infolded nuclei have also been reported to be associated with neuronal activity. Here, we performed time-lapse imaging in the visual cortex of Nex-Cre;SUN1-GFP mice. Nuclear infolding was observed within 10 min of stimulation in young nuclei, while the aged nuclei were already infolded pre-stimulation and showed reduced dynamics of the morphology. In young nuclei, the depletion of the stimuli restored the nucleus to a spherical shape and reduced the dynamic behavior, suggesting that nuclear infolding is a reversible process. We also found the aged nucleus to be stiffer than the young one, further relating to the age-associated loss of nuclear shape dynamics. We reveal temporal changes in the nuclear shape upon external stimulation and observe that these morphological dynamics decrease with age.

Efficacy and safety of tazobactam/ceftolozane in combination with metronidazole for intraabdominal infection in a hepato-biliary-pancreatic field in clinical practice.

INTRODUCTION: This single-center study evaluated the efficacy and safety of tazobactam/ceftolozane (TAZ/CTLZ) in combination with metronidazole for intraabdominal infection in a hepato-biliary-pancreatic field in clinical practice. METHODS: This study included 50 patients, including 35 with intraabdominal abscess or peritonitis, 5 with liver abscess, 4 with cholecystitis, and 6 with cholangitis with sepsis. Of the 50 patients, 29 received TAZ/CTLZ and metronidazole after a prior antibacterial therapy failure, including tazobactam/piperacillin, cefmetazole, and levofloxacin. Source control was performed in 36 patients. RESULTS: The clinical response could be evaluated in 49 patients. The clinical cure rate at end-of-therapy was 91.8% (45 of 49 patients) and that at test-of-cure was 89.6% (43 of 48 patients). Of 5 patients in whom clinical response at test-of-cure was a failure, 1 developed infectious disease during chemoradiotherapy for recurrent cancer and 4 after liver resection or pancreatoduodenectomy. Three of the 4 patients were associated with pancreatic juice leakage. Isolated pathogens were eradicated or presumably eradicated in 27 of 31 (87.1%) patients in whom microbiological response at test-of-cure could be evaluated. The response rate for AmpC-producing Enterobacteriaceae was 87.5%. Nausea was observed in two patients. Aspartate and alanine aminotransferase activities were increased in 3 of the 50 (6.0%) patients. The activities improved after the antibiotic discontinuation. CONCLUSIONS: This observational study demonstrated that TAZ/CTLZ in combination with metronidazole has a favorable effect without major drug-related adverse events for intraabdominal infection in the hepato-biliary-pancreatic field in clinical practice although the efficacy of TAZ/CTLZ may decrease in compromised patients.

[Electrocorticography Recorded from Subdural Electrodes and Stereo-Electroencephalography].

Epilepsy surgeons often encounter drug-resistant focal epilepsy, which needs to be diagnosed so that the epileptic foci can be identified and the patient treated. When noninvasive preoperative evaluation cannot determine the region of seizure onset or eloquent cortical areas, invasive epileptic video-EEG monitoring using intracranial electrodes needs to be applied. While subdural electrodes have been used to accurately identify epileptogenic foci via electrocorticography for some time, the use of stereo-electroencephalography has recently exploded in Japan, due to its less invasive nature and its better ability to reveal epileptogenic networks. This report describes the underlying concepts, indications, procedures, and contributions to neuroscience of both surgical procedures.

[A Study of the Safety of Chemotherapy with Generic Oxaliplatin for the Treatment of Colorectal Cancer].

BACKGROUND: Generic oxaliplatin is widely used in colorectal cancer chemotherapy; however, studies on the adverse events of generic drugs are limited. We investigated the safety of brand-name and generic oxaliplatin used in capecitabine plus oxaliplatin(plus bevacizumab: Bmab)for colorectal cancer treatment. PARTICIPANTS AND METHODS: A total of 86 patients who newly started CAPOX(plus Bmab)between January 2018 and January 2022 were included in this retrospective study, excluding those who changed to generic from the brand-name drug during the chemotherapy course. RESULTS: Forty-seven patients(54.6%)were in the generic drug(GE)group, while 39 patients(45.4%)were in the brand drug(EP)group. No significant difference was observed in the patient characteristics between the GE and EP groups. The median number of oxaliplatin administrations were 4 and 5 cycles in the GE and EP groups, respectively. Neutropenia of Grade 2 or higher was observed in 51.1%(24 patients)and 33.3%(13 patients)in the GE and EP groups, respectively. Hypersensitivity was observed in 14.9%(7 patients)and 7.7%(3 patients)in the GE and EP groups, respectively. CONCLUSION: There were no statistically significant differences between generic and brand-name oxaliplatin in the frequency of adverse events.