Case report of pharmacokinetic analysis of continuous intravenous infusion of fentanyl in a patient with severe burn: burn shock stage complicates pain management.

BACKGROUND: Fentanyl is widely used as an analgesic and sedative for patients with severe burn injuries in intensive care units. However, pharmacokinetic (PK) data for fentanyl, particularly for continuous intravenous infusion during the acute phase of burn injuries, are limited. Here, we report the clinical course and changes in blood fentanyl concentrations during the acute phase in a patient with severe burns treated with continuous intravenous infusion of fentanyl. CASE PRESENTATION: A woman in her 40s, with burns caused by a gas cylinder explosion, was transported to our hospital. The patient had burn wounds on face, neck, shoulders, and all four extremities, with a total burn area of 39.0%. For pain relief, the patient received a continuous infusion of 0.01 mg/mL fentanyl (20-30 µg/h) with a target blood concentration of 1.0-1.5 ng/mL, but continued to suffer from pain due to burning during the acute phase. We measured the blood fentanyl concentrations and found that all concentrations obtained during the acute phase were subtherapeutic. Notably, during the burn shock stage, blood concentrations of fentanyl were 0.50 ng/mL on day 1 and 0.66 ng/mL on day 2, indicating that the blood concentration did not rise sufficiently for the dosage. From days 0 to 2, the patient was administered a massive fluid load for burn shock. After the burn shock stage resolved, fentanyl concentrations gradually approached the target range, and the pain rating scale improved, even though the fentanyl administration rate remained unchanged (30 µg/h). CONCLUSIONS: Major changes in the fluid volumes of body compartments that occur with large burns might increase the volume of fentanyl distribution, thereby lowering its concentration when a standard dose is administered. Our findings indicate that the PK of fentanyl in patients with severe burns can be substantially affected, especially during the shock phase, implying the importance of titrating analgesics for clinical efficacy in the acute phase.

Assessing the ability of the Cancer and Aging Research Group tool to predict chemotherapy toxicity in older Japanese patients: A prospective observational study.

INTRODUCTION: The Cancer and Aging Research Group (CARG) prediction tool was designed in the United States to predict grade ≥ 3 chemotherapy-related adverse events (CRAE) in older patients. However, its usefulness among Japanese people, who have different sensitivities to anticancer drugs and life expectancy, remains unknown. We aimed to prospectively evaluate the utility of the CARG tool for predicting severe CRAE in older Japanese patients with cancer. MATERIAL AND METHODS: Patients with solid tumors aged 65 years and older who commenced anticancer drug regimens from April 2018 to October 2020 were divided into three groups (low, medium, and high-risk) based on their CARG risk scores. Toxicity was prospectively observed by a pharmacist. The primary objective was to evaluate the correlation between the incidence of grade ≥ 3 CRAE and the CARG risk score. The secondary objective was to evaluate hematological and non-hematological toxicities. CRAE incidence was compared among the three groups using a closed testing procedure: (1) Cochran-Armitage test for trend and (2) chi-square test for paired comparison. RESULTS: The patients (N = 165) had a median age of 71 years (range: 65-89 years). CRAE in patients divided into low-, medium-, and high-risk groups, based on CARG risk scores, were 39%, 55%, and 82%, respectively (low vs high; p < 0.001, medium vs high; p < 0.01). The incidence of severe hematologic toxicity was 37%, 35%, and 50% in the low-, medium-, and high-risk groups, respectively; the incidence of severe non-hematologic toxicity was 15%, 36%, and 65%, respectively (low vs medium; p < 0.01, low vs high; p < 0.001, and medium vs high; p < 0.01). DISCUSSION: To our knowledge, this is the first prospective observational study to validate the CARG prediction tool in older Japanese patients with cancer. The CARG risk score may be effective in predicting the development of non-hematologic toxicities. These results should be considered when administering chemotherapy to older Japanese patients with advanced solid tumors.

[Factors Associated with the Continuation of Anamorelin in Patients with Cancer-associated Cachexia: A Single-center Retrospective Study].

Cancer-associated cachexia, a multifactorial syndrome involving loss of muscle mass and anorexia, affects the survival of cancer patients. Anamorelin was the first drug approved in Japan for the treatment of cachexia. However, cases in which anamorelin is discontinued within 3 weeks are often observed in clinical practice. This study aimed to explore the factors associated with continued anamorelin dosing. We retrospectively reviewed records of patients with lung, gastric, pancreatic, and colorectal cancer who started anamorelin at Fukuoka University Hospital from April 2021 to November 2022. Patients were divided into two groups based on the duration of anamorelin administration: 15 patients were classified into the <3 weeks group and 22 were classified into the ≥3 weeks group. The primary objective was to explore the potential factors associated with the continuation of anamorelin, and the secondary objectives were to compare survival and nutritional indices. In the univariate analysis, there were significant differences between the two groups in terms of cancer type (p=0.007) and serum albumin level (p=0.026). In the multivariate analysis, gastric cancer and albumin 2.7 g/dL or less were associated with the continuation of anamorelin. Survival was significantly shorter in the <3 weeks group (p=0.019). This study suggests that the continuation of anamorelin may be influenced by specific tumor types and serum albumin levels. Furthermore, the duration of anamorelin administration may affect patient survival.

Comparison of preventive effects of combined furosemide and mannitol versus single diuretics, furosemide or mannitol, on cisplatin-induced nephrotoxicity.

Cisplatin (CDDP)-induced nephrotoxicity is a common dose-limiting toxicity, and diuretics are often administered to prevent nephrotoxicity. However, the efficacy and optimal administration of diuretics in preventing CDDP-induced nephrotoxicity remain to be established. This study aimed to evaluate the efficacy of combining furosemide and mannitol to prevent CDDP-induced nephrotoxicity. This was a post-hoc analysis of pooled data from a multicenter, retrospective, observational study, including 396 patients who received one or two diuretics for CDDP-based chemotherapy, compared using propensity score matching. Multivariate logistic regression analyses were used to identify risk factors for nephrotoxicity. There was no significant difference in the incidence of nephrotoxicity between the two groups (22.2% vs. 28.3%, P = 0.416). Hypertension, CDDP dose ≥ 75 mg/m2, and no magnesium supplementation were identified as risk factors for nephrotoxicity, whereas the use of diuretics was not found to be a risk factor. The combination of furosemide and mannitol showed no advantage over a single diuretic in preventing CDDP-induced nephrotoxicity. The renal function of patients receiving CDDP-based chemotherapy (≥ 75 mg/m2) and that of those with hypertension should be carefully monitored. Magnesium supplementation is important for these patients.

Increased risk of incisional hernia after stoma closure in patients with colorectal cancer.

PURPOSE: Stoma construction and closure are common surgical strategies in patients with colorectal cancer. The present study evaluated the influence of multiple incisional sites resulting from stoma closure on incisional hernia after colorectal cancer surgery. METHODS: The study included 1681 patients who underwent colorectal cancer surgery. Multiple incisional sites were defined as the coexistence of incisions at the midline and stoma closure sites. We retrospectively investigated the relationship between the presence of multiple incisional sites and incisional hernia development in patients with colorectal cancer. RESULTS: Among the 1681 patients, 420 (25%) underwent stoma construction, with a stoma closure-to-construction ratio of 33% (139/420), and 155 (9.2%) developed incisional hernias after colorectal cancer surgery. In the multivariate analysis, female sex (p < 0.001), body mass index (p < 0.001), multiple incisional sites (p = 0.001), wound infection (p = 0.003), and postoperative chemotherapy (p = 0.030) were independent predictors of incisional hernia. In the multiple incisional sites group, the age (p < 0.001), surgical approach (laparoscopic) (p = 0.013), wound infection rate (p = 0.046), small bowel obstruction rate (p < 0.001), and anastomotic leakage rate (p = 0.008) were higher in those in the single incisional site group. CONCLUSIONS: Multiple incisional sites resulting from stoma closure are associated with the development of incisional hernia following colorectal cancer surgery.

Prognostic usefulness of the C-reactive protein-albumin-lymphocyte (CALLY) index as a novel biomarker in patients undergoing colorectal cancer surgery.

BACKGROUND: The C-reactive protein (CRP)-albumin-lymphocyte (CALLY) index is a novel immuno-nutritional biomarker based on the levels of CRP, serum albumin, and lymphocyte count. This study examined the prognostic value of the CALLY index in patients with colorectal cancer undergoing curative surgery. METHODS: Between 2010 and 2017, 578 patients with stage II-III colorectal cancer who underwent curative resection were enrolled. The CALLY index was defined as (albumin × lymphocyte)/(CRP × 104). We investigated the association of the CALLY index with disease-free survival (DFS) and overall survival (OS). RESULTS: The cutoff value of the CALLY index was determined to be 2. Of the 578 patients, 175 (30%) had a preoperative CALLY index <2. In multivariate analysis, the pre-operative carcinoembryonic antigen (CEA) level (p = 0.003), cell differentiation (p = 0.045), venous invasion (p = 0.036), Tumor-Node-Metastasis stage (p < 0.001), and CALLY index score <2 (p = 0.006) were independent predictors of DFS. Meanwhile, preoperative carbohydrate antigen (CA)19-9 levels (p = 0.019), lymphatic invasion (p = 0.018), preoperative platelet (p = 0.037), and CALLY index score <2 (p = 0.007) were independent predictors of OS. CONCLUSION: The CALLY index may be an independent prognostic biomarker for long-term outcomes in patients with colorectal cancer.

Implementable assay for monitoring minimum residual disease after radical treatment for colorectal cancer.

Considering the cost and invasiveness of monitoring postoperative minimal residual disease (MRD) of colorectal cancer (CRC) after adjuvant chemoradiotherapy (ACT), we developed a favorable approach based on methylated circulating tumor DNA to detect MRD after radical resection. Analyzing the public database, we identified the methylated promoter regions of the genes FGD5, GPC6, and MSC. Using digital polymerase chain reaction (dPCR), we termed the "amplicon of methylated sites using a specific enzyme" assay as "AMUSE." We examined 180 and 114 pre- and postoperative serial plasma samples from 28 recurrent and 19 recurrence-free pathological stage III CRC patients, respectively. The results showed 22 AMUSE-positive of 28 recurrent patients (sensitivity, 78.6%) and 17 AMUSE-negative of 19 recurrence-free patients (specificity, 89.5%). AMUSE predicted recurrence 208 days before conventional diagnosis using radiological imaging. Regarding ACT evaluation by the reactive response, 19 AMUSE-positive patients during their second or third blood samples showed a significantly poorer prognosis than the other patients (p = 9E-04). The AMUSE assay stratified four groups by the altered patterns of tumor burden postoperatively. Interestingly, only 34.8% of cases tested AMUSE-negative during ACT treatment, indicating eligibility for ACT. The AMUSE assay addresses the clinical need for accurate MRD monitoring with universal applicability, minimal invasiveness, and cost-effectiveness, thereby enabling the timely detection of recurrences. This assay can effectively evaluate the efficacy of ACT in patients with stage III CRC following curative resection. Our study strongly recommends reevaluating the clinical application of ACT using the AMUSE assay.

Terrestrial predatory leeches of the genus Orobdella (Hirudinea: Erpobdelliformes: Orobdellidae) endemic to the Southern Russian Far East: a new species of the genus from Primorsky Krai, Russia.

A quadrannulate species, Orobdella ganini sp. nov., is described from the Lazovsky Nature Reserve in Primorsky Krai, the Southern Russian Far East, Russia. Morphological features of O. ghilarovi Nakano & Prozorova, 2019 from the reserve are also provided leading to an amendment of the species diagnosis. Maximum likelihood and Bayesian inference phylogenetic analyses, which were performed using nuclear 18S rRNA, 28S rRNA, and histone H3, and mitochondrial cytochrome c oxidase subunit I, tRNACys, tRNAMet, 12S rRNA, tRNAVal, 16S rRNA, tRNALeu and NADH dehydrogenase subunit 1 markers, show that O. ganini sp. nov., O. ghilarovi and two species endemic to Hokkaido, Japan form a clade, with the new species sister to a lineage composed of the two Japanese species. A partial cytochrome c oxidase subunit I sequence obtained from a cocoon found in the Lazovsky Nature Reserve reveals that Orobdella leeches deposit cocoons somewhat similar to those deposited by terrestrial blood-sucking leeches of Haemadipsidae.

Relictithismia kimotsukiensis, a new genus and species of Thismiaceae from southern Japan with discussions on its phylogenetic relationship.

The family Thismiaceae, known as "fairy lanterns" for their urn- or bell-shaped flowers with basally fused tepals, consists of non-photosynthetic flowering monocots mainly in tropical regions, extending into subtropical and temperate areas. Here, we propose a new mycoheterotrophic genus, Relictithismia Suetsugu & Tagane (Thismiaceae), with its monotypic species Relictithismia kimotsukiensis Suetsugu, Yas.Nakam. & Tagane from Kimotsuki Mountains in the Osumi Peninsula, Kagoshima Prefecture, Kyushu Island, southern Japan. Relictithismia resembles Haplothismia Airy Shaw in having a cluster of tuberous roots, a feature previously observed only in this genus within the family Thismiaceae. However, it differs in having solitary flowers (vs. 2-6-flowered pseudo-raceme in Haplothismia), anther thecae largely separated (vs. connate), and the presence of an annulus (vs. absent). Additionally, Relictithismia differs from the geographically overlapping genus Thismia Griff. in its stamen structure and the position of the annulus. In Relictithismia, the stamens lack connectives, and its free filaments arise from the annulus located inside the perianth mouth, while in Thismia, the stamens typically have connate connectives, forming a staminal tube pendulous from the annulus located at the mouth of the floral tube. Our morphological and phylogenetic data indicated that R. kimotsukiensis holds an early-diverging position within the family, situated outside the Old World Thismia clade. This paper offers an extensive description and color photographs of R. kimotsukiensis, complemented by notes on its phylogenetic relationship and evolutionary history.

High-output stoma is a risk factor for stoma outlet obstruction in defunctioning loop ileostomies after rectal cancer surgery.

PURPOSE: Defunctioning loop ileostomy has been reported to reduce symptomatic anastomotic leakage after rectal cancer surgery; however, stoma outlet obstruction (SOO) is a serious postileostomy complication. We, therefore, explored novel risk factors for SOO in defunctioning loop ileostomy after rectal cancer surgery. METHODS: This is a retrospective study that included 92 patients who underwent defunctioning loop ileostomy with rectal cancer surgery at our institution. Among them, 77 and 15 ileostomies were created at the right lower abdominal and umbilical sites, respectively. We defined the output volumeMAX as the maximum output volume the day before the onset of SOO or-for those without SOO-that was observed during hospitalization. Univariate and multivariate analyses were performed to evaluate risk factors for SOO. RESULTS: SOO was observed in 24 cases, and the median onset was 6 days postoperatively. The stoma output volume in the SOO group was consistently higher than that in the non-SOO group. In the multivariate analysis, the rectus abdominis thickness (p < 0.01) and output volumeMAX (p < 0.01) were independent risk factors for SOO. CONCLUSION: A high-output stoma may predict SOO in patients with defunctioning loop ileostomy for rectal cancer. Considering that SOO occurs even at umbilical sites with no rectus abdominis, a high-output stoma may trigger SOO primarily.

O-GlcNAcylation is essential for therapeutic mitochondrial transplantation.

BACKGROUND: Transplantation of mitochondria is increasingly explored as a novel therapy in central nervous system (CNS) injury and disease. However, there are limitations in safety and efficacy because mitochondria are vulnerable in extracellular environments and damaged mitochondria can induce unfavorable danger signals. METHODS: Mitochondrial O-GlcNAc-modification was amplified by recombinant O-GlcNAc transferase (OGT) and UDP-GlcNAc. O-GlcNAcylated mitochondrial proteins were identified by mass spectrometry and the antiglycation ability of O-GlcNAcylated DJ1 was determined by loss-of-function via mutagenesis. Therapeutic efficacy of O-GlcNAcylated mitochondria was assessed in a mouse model of transient focal cerebral ischemia-reperfusion. To explore translational potential, we evaluated O-GlcNAcylated DJ1 in CSF collected from patients with subarachnoid hemorrhagic stroke (SAH). RESULTS: We show that isolated mitochondria are susceptible to advanced glycation end product (AGE) modification, and these glycated mitochondria induce the receptor for advanced glycation end product (RAGE)-mediated autophagy and oxidative stress when transferred into neurons. However, modifying mitochondria with O-GlcNAcylation counteracts glycation, diminishes RAGE-mediated effects, and improves viability of mitochondria recipient neurons. In a mouse model of stroke, treatment with extracellular mitochondria modified by O-GlcNAcylation reduces neuronal injury and improves neurologic deficits. In cerebrospinal fluid (CSF) samples from SAH patients, levels of O-GlcNAcylation in extracellular mitochondria correlate with better clinical outcomes. CONCLUSIONS: These findings suggest that AGE-modification in extracellular mitochondria may induce danger signals, but O-GlcNAcylation can prevent glycation and improve the therapeutic efficacy of transplanted mitochondria in the CNS.

Mitochondria are the part of a cell that generate most of its energy to perform its functions. In injury or disease, mitochondrial function can become disrupted. Transplantation of healthy mitochondria is being explored as a potential therapy to replace damaged mitochondria and restore normal cellular function. However, this approach is difficult to perform because mitochondria are not able to maintain their healthy state outside of cells. Here, we show that one of the reasons for this is due to a molecular process called advanced glycation end product modification. We show that simple modification of mitochondria with a sugar prevents this process and helps to improve the success of therapeutic mitochondrial transplantation in cells and in a mouse model of stroke. Our findings may help to guide future efforts to develop therapies based on mitochondrial transplantation.

Efficacy of 3-day versus 5-day aprepitant regimens for long-delayed chemotherapy-induced nausea and vomiting in patients receiving cisplatin-based chemotherapy.

BACKGROUND: Chemotherapy-induced nausea and vomiting (CINV) is an ongoing problem. While effectiveness of triplet antiemetic regimens in the delayed CINV phase (24-120 hours after administration of chemotherapy) has been studied, their effectiveness in the long-delayed phase (120-168 hours post-administration) is unknown. We compared the efficacy of 3- and 5-day courses of a triplet antiemetic prophylaxis containing aprepitant (APR) in controlling long-delayed CINV after cisplatin (CDDP)-based chemotherapy. RESEARCH DESIGN AND METHODS: We obtained patient-level data from a nationwide, multicenter, prospective observational study in Japan. The incidence and timing of CINV after 3- and 5-day APR-containing regimens were compared using inverse probability treatment weighting. RESULTS: The analysis included 380 patients. The incidence rates of long-delayed nausea and vomiting were significantly reduced for the 5-day compared with the 3-day regimen (29.1% vs. 22.2%, p = 0.0042; 6.7% vs. 0%, p < 0.0001, respectively). Among those without CINV, vomiting was not reported after day 2 in the 5-day APR group but increased after day 4 in the 3-day APR group. CONCLUSION: A 5-day regimen triplet antiemetic prophylaxis with APR decreased long-delayed vomiting compared with a 3-day regimen in patients receiving CDDP-based chemotherapy. However, the 5-day regimen showed no advantage over the 3-day regimen against long-delayed nausea.

Clinical Significance of Controlling Nutritional Status (CONUT) Score in Patients With Colorectal Liver Metastases After Hepatectomy.

BACKGROUND/AIM: The prognostic outcome of the controlling nutritional status (CONUT) score in patients with colorectal liver metastases (CRLM) who underwent hepatectomy has not been investigated. The aim of this study was to investigate the prognostic value of preoperative CONUT score and other systemic inflammation-related biomarkers in patients who underwent hepatectomy for CRLM. PATIENTS AND METHODS: The subjects included 145 patients with CRLM who underwent hepatectomy and retrospectively investigated the association of preoperative CONUT score with disease-free survival (DFS), surgical failure-free survival (SFS), and overall survival (OS) using univariate and multivariate analyses. RESULTS: In this study, the cut-off of the CONUT score was 4. In the univariate analysis, the high CONUT score was associated with worse SFS and OS (p=0.01, 0.01). The multivariate analysis showed significant and independent predictors of OS were lymph node metastases (p=0.03) and a high CONUT score (p=0.04). In patients with a high CONUT score, postoperative complications due to infections were significantly more than in those with a low CONUT score (27% vs. 9%, p=0.04). CONCLUSION: The CONUT score can be useful for predicting not only short-term but also long-term outcomes in patients with CRLM after hepatectomy.

A new species of the genus Pseudocrangonyx (Crustacea: Amphipoda: Pseudocrangonyctidae) from subterranean waters of Japan.

A new species of pseudocrangonyctid amphipod, Pseudocrangonyx asuwaensis, is described from subterranean water in a quarry on Mt. Asuwa "Nanatsuo-guchi", Fukui Prefecture, Japan. Pseudocrangonyx asuwaensis sp. nov. differs from its congeners in various morphological features, such as head without eyes, relative length of antennae 1, female antenna 2 without calceoli, length ratio of mandibular palp articles, setal numbers on maxillae 1 and 2 inner plates, absence of sternal gills, armature of urosomite 1, and shape of telson. Molecular phylogenetic analyses suggest that P. asuwaensis sp. nov. is clustered with P. komaii Tomikawa & Nakano, 2018, Pseudocrangonyx sp. 7 and Pseudocrangonyx sp. 8, and was the first of these species to diverge.

A New Species of Branchellion (Hirudinea: Piscicolidae) Parasitizing the Gills of Short-Tail Stingrays (Batoidea: Dasyatidae) from the West Pacific.

A new fish leech, Branchellion brevicaudatae sp. n., is described based on specimens parasitizing the gills of the short-tail stingray, Bathytoshia brevicaudata (Hutton, 1875), collected from Japanese waters. The new species can be distinguished from other congeners by having: i) pulsating vesicles emerging from posterior base of branchiae, one pair per somite; ii) dorsal white spots, not arranged in longitudinal row; and iii) blackish body. A phylogenetic tree based on partial sequences of the mitochondrial cytochrome c oxidase subunit I gene from the new species and other piscicolid worms showed that the new species is sister to Branchellion torpedinis Savigny, 1822. This is the first record of Branchellion Savigny, 1822 from Japanese waters.

Adrenaline-resistant anaphylactic shock caused by contrast medium in a patient after risperidone overdose: a case report.

BACKGROUND: In Japan, the use of risperidone in combination with adrenaline is contraindicated, except in cases of anaphylaxis. Therefore, there is limited clinical evidence regarding the interaction of these two drugs. Here, we report the clinical course of a case of adrenaline-resistant anaphylactic shock induced by a contrast medium injection after a risperidone overdose. CASE PRESENTATION: A man in his 30s was transported to our hospital after attempting suicide by taking 10 mg of risperidone and jumping from a height of 10 m. To determine the location and severity of his injuries, he was injected with an iodinated contrast medium, after which he developed generalized erythema and hypotension and was diagnosed with anaphylactic shock. A 0.5 mg dose of adrenaline was administered with no improvement, followed by another 0.5 mg dose that did not change his blood pressure. After infusion of a sodium bicarbonate solution (8.4%), administration of fresh frozen plasma, and additional administration of adrenaline (0.6-1.2 µg/min), his blood pressure improved, and he recovered from the anaphylactic shock. CONCLUSIONS: This was a rare case of a risperidone overdose followed by adrenaline-resistant anaphylactic shock. The resistance is likely associated with the high blood concentration of risperidone. Our findings indicate that the potential for decreased adrenergic responsiveness should be considered in patients undergoing risperidone treatment in the event of anaphylactic shock.

Characteristics of Patients With Inflammatory Bowel Disease Who Develop Bloodstream Infection.

Background: The causative microorganisms of bloodstream infections (BSIs) in patients with inflammatory bowel disease (IBD) and the clinical characteristics of these patients have not yet been fully identified. Therefore, this study investigated IBD patients who developed BSI to determine their clinical characteristics and identify the BSI-causing bacteria. Methods: The subjects were IBD patients who developed bacteremia between 2015 and 2019 at Fukuoka University Chikushi Hospital. The patients were divided into two groups according to IBD type (Crohn's disease (CD) or ulcerative colitis (UC)). The medical records of the patients were reviewed to determine their clinical backgrounds and identify the BSI-causing bacteria. Results: In total 95 patients, 68 CD and 27 UC patients were included in this study. The detection rates of Pseudomonas aeruginosa (P. aeruginosa) and Klebsiella pneumoniae (K. pneumoniae) were higher in the UC group than in the CD group (18.5% vs. 2.9%, P = 0.021; 11.1% vs. 0%, P = 0.019, respectively). Immunosuppressive drugs use was higher in the CD group than in the UC group (57.4% vs. 11.1%, P = 0.00003). Hospital stay length was longer in the UC group than in the CD group (15 vs. 9 days; P = 0.045). Conclusions: The causative bacteria of BSI and clinical backgrounds differed between patients with CD and UC. This study showed that P. aeruginosa and K. pneumoniae had higher abundance in UC patients at the onset of BSI. Furthermore, long-term hospitalized patients with UC required antimicrobial therapy against P. aeruginosa and K. pneumoniae.

Comparison of the cytokine adsorption ability in continuous renal replacement therapy using polyethyleneimine-coated polyacrylonitrile (AN69ST) or polymethylmethacrylate (PMMA) hemofilters: a pilot single-center open-label randomized control trial.

BACKGROUND: Sepsis occurs as a result of dysregulated host response to infection. However, cytokine adsorption therapy may restore the balance of proinflammatory and anti-inflammatory mediator responses in patients with sepsis. This study aimed to determine the cytokine adsorption ability of two different types of continuous renal replacement therapy (CRRT) hemofilters for polyethyleneimine-coated polyacrylonitrile (AN69ST) (surface-treated) and polymethylmethacrylate (PMMA) CRRT. METHODS: We performed a randomized controlled trial among sepsis patients undergoing CRRT, who were randomly assigned (1:1) to receive either AN69ST or PMMA-CRRT. The primary outcome was cytokine clearance of hemofilter adsorption (CHA). The secondary endpoints were the intensive care unit (ICU) and 28-day mortalities. RESULTS: We randomly selected 52 patients. Primary outcome data were available for 26 patients each in the AN69ST-CRRT and PMMA-CRRT arms. The CHA of high-mobility group box 1, tumor necrosis factor, interleukin (IL)-8, monokine induced by interferon-γ, and macrophage inflammatory protein were significantly higher in the AN69ST-CRRT group than in the PMMA-CRRT group (P < 0.001, P < 0.01, P < 0.001, P < 0.001 and P < 0.001, respectively). In contrast, the CHA of IL-6 was significantly higher in the PMMA-CRRT group than in the AN69ST-CRRT group (P < 0.001). In addition, the 28-day mortality was not significantly different between the two groups (50% in AN69ST-CRRT vs. 30.8% in PMMA-CRRT, P = 0.26). CONCLUSION: AN69ST and PMMA membranes have different cytokine CHA in patients with sepsis. Therefore, these two hemofilters may have to be used depending on the target cytokine. TRIAL REGISTRATION NUMBER: This study was registered in the University Hospital Medical Information Network on November 1, 2017 (Trial No: UMIN000029450, https://center6.umin.ac.jp ).

Effectiveness of Palonosetron, 1-Day Dexamethasone, and Aprepitant in Patients Undergoing Carboplatin-Based Chemotherapy.

INTRODUCTION: Dexamethasone (DEX)-sparing strategy with 5-hydroxytryptamine-3 receptor antagonist (5HT3RA) and aprepitant (APR), as triplet antiemetic prophylaxis, is associated with poor control of delayed chemotherapy-induced nausea and vomiting (CINV) in patients receiving carboplatin (CBDCA)-based chemotherapy. This study aimed to evaluate whether using palonosetron (PALO) as a 5HT3RA provides superior control with CINV than first-generation (1st) 5HT3RA in triplet antiemetic prophylaxis with a DEX-sparing strategy. METHODS: Pooled patient-level data from a nationwide, multicenter, and prospective observational study were analyzed to compare the incidence of CINV between patients administered PALO and 1st 5HT3RA in combination with 1-day DEX and APR. RESULTS: No significant differences were observed in the incidence of CINV, pattern of CINV, or severity of nausea by type of 5HT3RA in triplet antiemetic prophylaxis with DEX-sparing strategy. In both groups, the incidence of nausea gradually increased from day 3, peaked on day 4 or 5, and then declined slowly. The visual analog scale scores in the delayed phase remained high throughout the 7-day observation period. CONCLUSION: Careful patient selection and symptom monitoring are needed when implementing the DEX-sparing strategy in triplet antiemetic prophylaxis for patients undergoing CBDCA-based chemotherapy. Furthermore, additional strategies may be needed to achieve better control of delayed CINV.

Immune Checkpoint Inhibitors for Nasopharyngeal Carcinoma in a Real-world Setting in Japan.

BACKGROUND/AIM: The advent of immune checkpoint inhibitor (ICI) treatment has transformed the treatment of recurrent or metastatic head and neck cancer; however, nasopharyngeal carcinoma (NPC) has not been included in major phase III trials. The clinical outcomes of ICI for NPC in real-world practice remain to be fully elucidated. PATIENTS AND METHODS: We retrospectively reviewed 23 patients with recurrent or metastatic NPC treated with nivolumab or pembrolizumab at 6 institutions from April 2017 to July 2021 and investigated the correlation of clinicopathological factors and immune-related adverse events with the effects of ICI therapy and the prognosis. RESULTS: The objective response rate was 39.1% and the disease control rate was 78.3%. The median progression-free survival was 16.8 months and overall survival has not been reached. As with other treatment procedures, the efficacy and the prognosis tended to be better in EBER-positive cases than in EBER-negative cases. The rate of significant immune-related adverse events that necessitated discontinuation of treatment was only 4.3%. CONCLUSION: ICI monotherapy (e.g., nivolumab and pembrolizumab) was effective and tolerable for NPC in a real-world setting.