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Abstract Background Fat embolism syndrome (FES) is a rare syndrome that typically occurs 12–72 h after long bone or pelvic fractures with a classic triad of respiratory distress, neurologic changes, and petechial rash. Although Gurd’s criteria for FES include anuria or oliguria, the mechanism of acute kidney injury (AKI) remain unknown. Here, we present a case of FES complicated by AKI that required blood purification. Case presentation A 79-year-old woman was admitted to our hospital because of a right humerus and pelvic fracture caused by a traffic accident. On the second day of hospitalization, she developed impaired consciousness, respiratory failure, and disseminated intravascular coagulation (DIC). Chest radiography revealed bilateral diffuse alveolar infiltration. Brain magnetic resonance imaging revealed diffuse high signal intensity on diffusion-weighted imaging and diffuse low signal intensity on susceptibility-weighted imaging in the cerebral and cerebellar regions. The diagnosis of FES was confirmed and the patient was treated with methylprednisolone (40 mg/day) and ulinastatin. On the third day of hospitalization, she was admitted to our department because of AKI with oliguria. Although echocardiography showed an elevated right ventricular artery systolic pressure suggestive of pulmonary hypertension (PH), pulmonary congestion was initially considered on chest imaging, and hemodialysis and rapid ultrafiltration were initiated. However, she developed hypovolemic shock and treatment was switched to continuous hemodiafiltration and slow ultrafiltration. Thereafter, her consciousness, hypoxemia, DIC and PH completely improved. She was weaned from blood purification therapy on the 29th day of hospitalization. She had hemolytic anemia that might have been caused by thrombotic microangiopathy (TMA), but it resolved without plasmapheresis. On the 51st day of hospitalization, the patient was transferred to another hospital for rehabilitation. Conclusions FES can be complicated by AKI. In this case, DIC, which was difficult to differentiate from TMA, and/or renal congestion were considered to be a cause of AKI. Chest radiographs of FES may be indistinguishable from pulmonary congestion. In our case, chest radiography showed bilateral diffuse alveolar infiltrates which was not indicative of pulmonary congestion but pulmonary involvement of FES. FES is associated with PH, which may lead to right heart failure. Therefore, the patient could have developed hypovolemic shock due to hemodialysis and rapid ultrafiltration. Clinicians should pay attention to the hemodynamics when blood purification for FES is performed.

Abstract Background Cardiac surgery is performed worldwide, and acute kidney injury (AKI) following cardiac surgery is a risk factor for mortality. However, the optimal blood pressure target to prevent AKI after cardiac surgery remains unclear. We aimed to investigate whether relative hypotension and other hemodynamic parameters after cardiac surgery are associated with subsequent AKI progression. Methods We retrospectively enrolled adult patients admitted to 14 intensive care units after elective cardiac surgery between January and December 2018. We defined mean perfusion pressure (MPP) as the difference between mean arterial pressure (MAP) and central venous pressure (CVP). The main exposure variables were time-weighted-average MPP-deficit (i.e., the percentage difference between preoperative and postoperative MPP) and time spent with MPP-deficit > 20% within the first 24 h. We defined other pressure-related hemodynamic parameters during the initial 24 h as exploratory exposure variables. The primary outcome was AKI progression, defined as one or more AKI stages using Kidney Disease: Improving Global Outcomes’ creatinine and urine output criteria between 24 and 72 h. We used multivariable logistic regression analyses to assess the association between the exposure variables and AKI progression. Results Among the 746 patients enrolled, the median time-weighted-average MPP-deficit was 20% [interquartile range (IQR): 10–27%], and the median duration with MPP-deficit > 20% was 12 h (IQR: 3–20 h). One-hundred-and-twenty patients (16.1%) experienced AKI progression. In the multivariable analyses, time-weighted-average MPP-deficit or time spent with MPP-deficit > 20% was not associated with AKI progression [odds ratio (OR): 1.01, 95% confidence interval (95% CI): 0.99–1.03]. Likewise, time spent with MPP-deficit > 20% was not associated with AKI progression (OR: 1.01, 95% CI 0.99–1.04). Among exploratory exposure variables, time-weighted-average CVP, time-weighted-average MPP, and time spent with MPP

Abstract Background Chemotherapy-induced peripheral neuropathy (CIPN) is a painful, dose-limiting adverse effect of commonly used chemotherapeutic agents. The purpose of this exploratory study was to evaluate the efficacy and safety of mirogabalin in patients with moderate to severe CIPN during chemotherapy and the effects of 12 weeks’ intervention on chemotherapy completion and CIPN severity. Methods Patients experiencing moderate to severe CIPN while undergoing oxaliplatin- or taxane-containing chemotherapy for colorectal, gastric, non-small-cell lung, or breast cancer received mirogabalin at between 5 and 15 mg twice daily. The primary endpoint was change in numeric rating scale (NRS) score for pain from baseline to week 12. Secondary endpoints included NRS scores for tingling and sleep, completion of chemotherapy, severity of CIPN, and quality of life (QOL) scores. The safety endpoint was incidence of adverse events. Results Of 58 patients who consented to participation, 52 were eligible and constituted the full analysis set and safety analysis set. From baseline to week 12 (last observation carried forward [LOCF]), NRS score decreased by 30.9%: mean change (95% confidence interval [CI]), − 1.7 (− 2.4 to − 1.0) (p

Abstract Immune checkpoint inhibitor (ICI) therapy is often associated with cutaneous immune‐related adverse events (irAEs). Drug eruptions stemming from concomitantly or consecutively administered medications are also frequent and tend to be severe. We herein present three cases of severe drug eruption in patients receiving antibiotics during ICI therapy in which hypotensive shock occurring during antibiotic administration was followed by generalized erythema and prolonged organ damage. Three patients received tazobactam/piperacillin (TAZ/PIPC) for an infection during ICI treatment. A high fever developed in all the patients after a switch was made to other antibiotics (Figures 2–4). Since no skin rash was observed at fever onset, a flare‐up of the infection was suspected, and TAZ/PIPC administration was resumed. Thereafter, the patients suddenly experienced hypotensive shock and respiratory failure requiring ICU management for generalized erythema and organ damage. Since anaphylaxis caused by TAZ/PIPC is rare, the patients’ clinical findings might be a manifestation of synergistic, complementary, immunomodulatory effects of ICI. In patients receiving ICI therapy, a fever occurring during antibiotic administration may indicate the onset of an immune hypersensitivity reaction to the drug. Resumption of antibiotic administration, especially TAZ/PIPC, during such a period may trigger an excessive inflammatory response, leading to an anaphylaxis‐like reaction and organ damage.

BackgroundChemotherapy-induced peripheral neuropathy (CIPN) is one of the most common adverse events that can significantly impair the quality of life of patients. Although limb cooling may be beneficial for preventing CIPN, logistical challenges exist in ensuring consistent efficacy and safety. The purpose of this randomized controlled trial is to validate whether limb cooling with strict temperature control can reduce CIPN in patients with breast cancer receiving weekly paclitaxel as a perioperative treatment.MethodsThis study is a multicenter, double-blinded, randomized controlled trial. We plan to enroll patients with breast cancer who are scheduled to receive 12 weekly doses of paclitaxel (60 min 80 mg/m2 intravenous infusion) as perioperative chemotherapy. Patients will be randomly divided into the intervention or control groups and undergo limb cooling therapy maintained at a constant temperature of 13°C and 25°C, respectively. The primary endpoint is the proportion of patients who report Patient Neurotoxicity Questionnaire (PNQ) ≥ D in their limbs by the end of the study treatment or at the time of discontinuation.DiscussionThe results of this trial will contribute to the establishment of new evidence for limb cooling therapy in the mitigation of CIPN and present a safe and stable cooling device that may be suitable for use in the clinic.Clinical trial registrationhttps://jrct.niph.go.jp/en-latest-detail/jRCT2032210115, identifier jRCT2032210115.

Abstract Background Higher body mass index (BMI) is associated with worse prognosis in pre‐ and postmenopausal patients with breast cancer (BC). However, there is insufficient evidence regarding the optimal adjuvant endocrine therapy for obese premenopausal women with hormone receptor (HR)‐positive BC. Aim To evaluate the impact of obesity and adjuvant endocrine therapy on prognosis in premenopausal patients with BC. Methods and results We retrospectively reviewed the medical record of premenopausal women who received curative surgery for clinical stage I–III HR‐positive BC from 2007 to 2017. Patients were classified into five groups according to BMI: underweight (UW), normal weight (NW), obese 1 degree (OB1), obese 2 degree (OB2), and obese 3 degree (OB3) categories. The primary analysis was a comparison of BC‐specific survival (BCSS) according to BMI (UW/NW vs. OB1–3) and adjuvant endocrine therapy (with or without ovarian function suppression [OFS]). Of 13 021 patients, the data of 3380 patients were analyzed. BCSS in OB1–3 patients was significantly worse than that in patients with UW/NW (hazard ratio [HR] 2.37; 95% confidence interval [CI], 1.40–4.02: p = .0009). In OB1–3 patients who received tamoxifen (TAM), BCSS was significantly worse than that in UW/NW patients (p = .0086); however, a significant difference was not shown in patients who received TAM and OFS (p = .0921). Conclusion High BMI was associated with worse prognosis in premenopausal patients with HR‐positive BC who received adjuvant TAM. The role of OFS as adjuvant endocrine therapy remains unclear, and further studies are required to explore the adequate management of obese premenopausal patients.

Abstract Talimogene laherparepvec (T-VEC) is an immunotherapy that generates local tumor lysis and systemic antitumor immune response. We studied the efficacy of intratumoral administration of T-VEC as monotherapy for inoperable locoregional recurrence of breast cancer. T-VEC was injected intratumorally at 106 PFU/mL on day 1 (cycle 1), 108 PFU/mL on day 22 (cycle 2), and 108 PFU/mL every 2 weeks thereafter (cycles ≥ 3). Nine patients were enrolled, 6 with only locoregional disease and 3 with both locoregional and distant disease. No patient completed the planned 10 cycles or achieved complete or partial response. The median number of cycles administered was 4 (range, 3–8). Seven patients withdrew prematurely because of uncontrolled disease progression, 1 withdrew after cycle 3 because of fatigue, and 1 withdrew after cycle 4 for reasons unrelated to study treatment. Median progression-free survival and overall survival were 77 days (95% CI, 63–NA) and 361 days (95% CI, 240–NA). Two patients received 8 cycles with clinically stable disease as the best response. The most common grade 2 or higher adverse event was injection site reaction (n = 7, 78%). Future studies could examine whether combining intratumoral T-VEC with concurrent systemic therapy produces better outcomes.

Abstract Background Among patients with colorectal cancer (CRC) treated with oxaliplatin (L-OHP)-based chemotherapy, delayed chemotherapy-induced nausea and vomiting (CINV) have not been well controlled. Methods We pooled data from two prospective observational studies in Japan and one phase III clinical trial to assess whether delayed CINV could be controlled with a combination of three antiemetics adding a neurokinin-1 receptor antagonist and identified individual risk factors, using an inverse probability treatment-weighted analysis. Results A total of 661 patients were evaluable in this study (median age: 64 years; 391 male, and 270 female). 3 antiemetics controlled delayed nausea (33.18% vs. 42.25%; p = 0.0510) and vomiting (4.15% vs. 16.08%; p

Background: Visceral crisis in metastatic breast cancer (MBC) is defined as severe organ dysfunction requiring rapidly efficacious therapy. Although weekly paclitaxel plus bevacizumab (wPTX + BV) achieves a high response rate in human epidermal growth factor receptor 2 (HER2)-negative MBC, the efficacy and safety of wPTX + BV for visceral crisis is unclear. Methods: We retrospectively investigated patients with MBC with visceral crisis who received wPTX + BV. Visceral crisis was defined as follows: liver dysfunction (aspartate or alanine aminotransferase >200 U/L or total bilirubin >1.5 mg/dl), respiratory dysfunction (carcinomatous lymphangiomatosis, SpO2

Abstract The human AlkB homolog family (ALKBH) of proteins play a critical role in some types of cancer. However, the expression and function of the lysine demethylase ALKBH4 in cancer are poorly understood. Here, we examined the expression and function of ALKBH4 in non-small-cell lung cancer (NSCLC) and found that ALKBH4 was highly expressed in NSCLC, as compared to that in adjacent normal lung tissues. ALKBH4 knockdown significantly induced the downregulation of NSCLC cell proliferation via cell cycle arrest at the G1 phase of in vivo tumour growth. ALKBH4 knockdown downregulated E2F transcription factor 1 (E2F1) and its target gene expression in NSCLC cells. ALKBH4 and E2F1 expression was significantly correlated in NSCLC clinical specimens. Moreover, patients with high ALKBH4 expression showed a poor prognosis, suggesting that ALKBH4 plays a pivotal tumour-promoting role in NSCLC.

Noble metals in waste liquid discharged from a metal plating process are landfilled as sludge formed by neutralization precipitation. In order to utilize this resource, we have attempted to recover nickel from waste liquid by electrolysis. The efficiency of nickel recovery is impaired by decreasing pH in electrolysis due to the use of an insoluble anode. To maintain the pH of the electrolyte, we introduced an anion exchange membrane into the recovery device. As a result, we confirmed recovery of 98% nickel from waste liquid. [ABSTRACT FROM AUTHOR]

Intestinal perforation is a rare adverse event of antineoplastic therapy. However, once it occurs, it is potentially fatal. This report describes a case of intestinal perforation caused by bevacizumab in a patient with ovarian cancer who concurrently developed neutropenic enterocolitis. A 66-year-old woman diagnosed with metastatic ovarian cancer received combination chemotherapy with carboplatin, gemcitabine, and bevacizumab. On day 14, she developed grade 4 pancytopenia and febrile neutropenia, which resulted in neutropenic enterocolitis and intestinal perforation. Emergency surgery was performed, and an intestinal perforation found in the ascending colon was closed. Postoperatively, she developed an intra-abdominal abscess requiring peritoneal drainage. She was discharged from the hospital on recovery.

To address whether expression of the relevant MHC molecules on thymic epithelial cells (TEC) is sufficient for positive selection, the fate of CD4+ T cells directed by the DRαEβb molecule was compared between two lines of HLA-DRA transgenic mice, DRα-24 expressing DRαEβb on TEC and hematopoietic cells, and DRα-30 expressing the molecule on TEC but not on other cell lineages. CD4+ T cells were selected to mature on DRαEβb molecules in both lines deficient for the endogenous MHC class I and class II molecules, whereas CD4+ T cell differentiation in DRα-30, as compared with that in DRα-24, was severely impaired when these mice were crossed with mice transgenic for the DRαEβb-restricted αβ TCR. In contrast, CD4+ T cells expressing the same TCRαβ as the transgenes were selected to mature in DRα-30 crossed with the single TCRβ transgenic mice. Taken together, these results indicate that the restricted expression of DRαEβb on TEC is sufficient for positive selection in the TCRβ and non-TCR transgenic mice, but the expression on both TEC and hematopoietic cells is required for that in the TCRαβ transgenic mice. In the light of the difference in the developmental stage at which αβ TCR are expressed between TCRαβ and TCRβ transgenic mice, the interaction of the TCRαβ with DRαEβb molecules expressed on hematopoietic cells required for positive selection in TCRαβ transgenic mice could be mapped to the early stage of T cell differentiation and might mimic ‘undefined’ early signaling of thymocytes in physiological T cell differentiation. [ABSTRACT FROM AUTHOR]