Late Kidney Injury After Admission to Intensive Care Unit for Acute Heart Failure.

Late kidney injury (LKI) in patients with acute heart failure (AHF) requiring intensive care is poorly understood.We analyzed 821 patients with AHF who required intensive care. We defined LKI based on the ratio of the creatinine level 1 year after admission for AHF to the baseline creatinine level. The patients were categorized into 4 groups based on this ratio: no-LKI (< 1.5, n = 509), Class R (risk; ≥ 1.5, n = 214), Class I (injury; ≥ 2.0, n = 78), and Class F (failure; ≥ 3.0, n = 20). Median follow-up after admission for AHF was 385 (346-426) days. Multivariate logistic regression analysis revealed that acute kidney injury (AKI) during hospitalization (Class R, odds ratio [OR]: 1.710, 95% confidence interval [CI]: 1.138-2.571, P = 0.010; Class I, OR: 6.744, 95% CI: 3.739-12.163, P < 0.001; and Class F, OR: 9.259, 95% CI: 4.078-18.400, P < 0.001) was independently associated with LKI. Multivariate Cox regression analysis showed that LKI was an independent predictor of 3-year all-cause death after final follow-up (hazard ratio: 1.545, 95% CI: 1.099-2.172, P = 0.012). The rate of all-cause death was significantly lower in the no-AKI/no-LKI group than in the no-AKI/LKI group (P = 0.048) and in the AKI/no-LKI group than in the AKI/LKI group (P = 0.017).The incidence of LKI was influenced by the presence of AKI during hospitalization, and was associated with poor outcomes within 3 years of final follow-up. In the absence of LKI, AKI during hospitalization for AHF was not associated with a poor outcome.

Ten-year trends in non-surgical patients requiring intensive care: Long-term prognostic differences by year of admission.

BACKGROUND: The aim of the present study is to elucidate prognostic impact of temporal trends of non-surgical patients requiring intensive care over a 10-year period. METHODS AND RESULTS: A total of 4276 non-surgical patients requiring intensive care from 2012 to 2021 were enrolled. Patients' backgrounds, in-hospital management, and prognoses were compared between five groups [2012-2013 (n = 825), 2014-2015 (n = 784), 2016-2017 (n = 864), 2018-2019 (n = 939), and 2020-2021 (n = 867)]. During the study period, mean age significantly increased from 69 years in 2012-2013 to 72 years in 2020-2021. Mean Acute Physiology and Chronic Health Evaluation scores significantly increased from 10 points in 2012-2013 to 12 points in 2020-2021. The median duration of intensive care unit stays increased from 3 to 4 days. Kaplan-Meier survival curve analysis showed that survival rates during 30- and 365-days were significantly lower in 2020-2021 than in 2012-2013, but it was not significantly different by a Cox proportional hazards regression model in 30 days. A Cox proportional hazards regression model revealed that the risks of 365-day all-cause death were significantly higher in patients enrolled in 2016-2017 (HR: 1.324, 95 % CI: 1.042-1.680, p = 0.021), in 2018-2019 (HR: 1.329, 95 % CI: 1.044-1.691, p = 0.021), and in 2020-2021 (HR: 1.409, 95 % CI: 1.115-1.779, p = 0.004). CONCLUSION: The condition of patients requiring intensive care is becoming more critical year by year, leading to poorer long-term prognoses despite improvements in treatment strategies. These findings emphasize the importance of additional care management after admission into non-surgical intensive care units, particularly for the aging society of Japan.

Impact of previous anthracycline therapy in patients with acute myeloid leukemia receiving venetoclax.

Venetoclax (VEN) combination regimens are now recognized as effective against acute myeloid leukemia (AML). However, the prognosis of patients who do not attain a composite complete response (cCR) is extremely poor, and clinical determinants of response remain unknown. Medical records of 57 patients with AML treated with VEN combination regimens from April 2021 to March 2022 at six institutions were retrospectively analyzed. The primary endpoint was cCR, complete remission, or complete remission with incomplete hematologic recovery after one cycle of VEN combination regimen. Five patients had previously relapsed after allogeneic hematopoietic stem cell transplantation (allo-SCT). The treatment regimen was azacitidine-VEN in 48 patients (84%) and low-dose cytarabine-VEN in 9 patients (16%). Thirty patients (53%) achieved cCR after one cycle of a VEN regimen. In univariate analysis, the number of prior chemotherapy regimens, post-allo-SCT relapse, and cytogenetic risk category were associated with a decreased likelihood of achieving cCR. In multivariate analysis, second-line chemotherapy remained a significant predictor of response. Patients who received anthracycline immediately before the VEN regimen had a higher cCR rate than patients who did not receive anthracycline. In this study, prior chemotherapy/allo-SCT and cytogenetic risk were associated with VEN treatment outcomes.

Risk factors for lower respiratory tract disease and outcomes in allogeneic hematopoietic stem cell transplantation recipients with influenza virus infection.

INTRODUCTION: Influenza virus infection (IVI) is frequent in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients, and reports from several countries indicate high morbidity and mortality from progression to lower respiratory tract disease (LRTD). However, there have been no reports on IVI clinical characteristics, treatment outcomes, and risk factor for progression to LRTD among allo-HSCT recipients in Japan. METHODS: We retrospectively reviewed the medical charts of allo-HSCT recipients who developed IVI between 2012 and 2019. RESULTS: Forty-eight cases of IVI following allo-HSCT were identified at our institution. The median age was 42 years, and median time from allo-HSCT to IVI was 25 months. Thirty-seven patients (77.1%) were administered neuraminidase inhibitors (NAIs) as antiviral therapy within 48 h of symptom onset (early therapy), whereas 11 (22.9%) received NAI over 48 h after onset (delayed therapy). Subsequently, 12 patients (25.0%) developed LRTD after IVI. Multivariate analysis identified older age (hazard ratio [HR], 7.65; 95% confidence interval [CI], 2.22-26.3) and bronchiolitis obliterans (HR, 5.74; 95% CI, 1.57-21.0) as independent risk factors for progression to LRTD. Moreover, land-mark analysis showed that early therapy prevented progression to LRTD (11.8% vs. 45.5%, P = 0.013). The IVI-related mortality rate was 2.1%. CONCLUSIONS: Early NAI treatment is recommended for reducing the risk of LRTD progression due to IVI in allo-HSTC recipients, particularly for older patients and those with bronchiolitis obliterans.

Pterostilbene downregulates BCR/ABL and induces apoptosis of T315I-mutated BCR/ABL-positive leukemic cells.

In this study, we examined the antileukemic effects of pterostilbene, a natural methylated polyphenol analog of resveratrol that is predominantly found in berries and nuts, using various human and murine leukemic cells, as well as bone marrow samples obtained from patients with leukemia. Pterostilbene administration significantly induced apoptosis of leukemic cells, but not of non-malignant hematopoietic stem/progenitor cells. Interestingly, pterostilbene was highly effective in inducing apoptosis of leukemic cells harboring the BCR/ABL fusion gene, including ABL tyrosine kinase inhibitor (TKI)-resistant cells with the T315I mutation. In BCR/ABL+ leukemic cells, pterostilbene decreased the BCR/ABL fusion protein levels and suppressed AKT and NF-κB activation. We further demonstrated that pterostilbene along with U0126, an inhibitor of the MEK/ERK signaling pathway, synergistically induced apoptosis of BCR/ABL+ cells. Our results further suggest that pterostilbene-promoted downregulation of BCR/ABL involves caspase activation triggered by proteasome inhibition-induced endoplasmic reticulum stress. Moreover, oral administration of pterostilbene significantly suppressed tumor growth in mice transplanted with BCR/ABL+ leukemic cells. Taken together, these results suggest that pterostilbene may hold potential for the treatment of BCR/ABL+ leukemia, in particular for those showing ABL-dependent TKI resistance.

Lasso loop technique using bioabsorbable thread to treat intra-articular distal radius fracture.

ABSTRACT: This article introduces our lasso loop technique (LLT) using a bioabsorbable thread for the treatment of intra-articular distal radius fractures with displaced dorsal bone fragment containing articular surface (DBF). We also examined whether the articular gap is sufficiently reduced and maintained by the LLT, along with the results of other radiological and clinical evaluations. We retrospectively reviewed 19 patients who underwent LLT for intra-articular distal radius fracture with a displaced DBF. Patient radiographic images and medical records were used to investigate radiological characteristics, symptoms, physical findings, and the Quick Disabilities of the Arm, Shoulder, and Hand scores. Sagittal-view computed tomography showed that the mean preoperative articular gap was 2.6 mm, but the gap was reduced by LLT, and the gap immediately postoperatively was <1.0 mm in all patients. No re-displacement of the DBF was evident from immediately postoperatively to 6 months postoperatively. Postoperatively, no losses of correction in palmar tilt, radial inclination, or ulnar variance were seen in the evaluation of plain radiographs, and satisfactory joint range of motion, grip strength, and the Quick Disabilities of the Arm, Shoulder, and Hand score were obtained. No significant complications due to LLT were observed. LLT appears to offer a simple and effective procedure to reduce displaced DBF with little risk of complications. LLT may become a useful option in the treatment of intra-articular distal radius fractures with displaced DBF.

Prosthetic joint infection after total hip arthroplasty caused by Sneathia sanguinegens: A case report (CARE-complaint).

INTRODUCTION: Sneathia sanguinegens(S sanguinegens) is a gram-negative rod-shaped bacterium mostly reported to cause a perinatal infection, and there are no reports of S sanguinegens in prosthetic joint infection (PJI). The purpose of this report is to describe a very rare case of PJI after total hip arthroplasty (THA) caused by S sanguinegens. PATIENT CONCERNS: A 79-year-old woman presented with right coxalgia, inability to walk, and a fever of 39°C. She had undergone THA 28 years earlier for osteoarthritis of the hip. DIAGNOSES: The diagnosis was acute late-onset PJI, because blood tests revealed marked inflammatory reaction and computed tomography showed an abscess at the right hip joint; synovial fluid analysis resulted in detection of a gram-negative bacillus. INTERVENTION: Surgical debridement with retention of the implant and antibiotic therapy was performed. OUTCOMES: One month after surgery, polymerase chain reaction (PCR) assay showed that the pathogen was 99.9% likely to be S sanguinegens. There has been no recurrence of infection or loosening of the implant in the 2 years since her surgery. LESSONS: PCR should facilitate detection of previously unknown pathogens and potentially novel bacterial species.

A Case of Composite Lymphoma with Extranodal NK/T-cell Lymphoma, Nasal-type and Diffuse Large B-cell Lymphoma.

Composite lymphoma (CL) is defined as the occurrence of two distinct types of lymphoma within the same patient. Most cases of CL involve Hodgkin and non-Hodgkin lymphomas or two distinct types of B-cell lymphomas; true CL is a composite B-cell and T-cell lymphoma, and is rare. We herein report a case involving concurrent extranodal NK/T-cell lymphoma, nasal-type and diffuse large B-cell lymphoma, which has not been previously reported. As the mechanisms and treatments of composite B-cell and T-cell lymphomas are unclear, further studies are required to improve the prognosis.

Primary CNS post-transplant lymphoproliferative disorder following haploidentical HSCT using post-transplant high-dose cyclophosphamide.

Neurological complications after hematopoietic stem cell transplantation (HSCT) are frequently life-threatening, and their clinical management can be highly challenging. In the case of central nervous system lesions post-HSCT, a definitive diagnosis is often difficult to reach because many different causative and contributing conditions may be present, including bacterial, fungal, or viral infections; original disease relapse; and post-transplant lymphoproliferative disorder (PTLD). Here, we report a case of a 32-year-old male patient with Philadelphia chromosomepositive acute lymphoid leukemia who underwent three HSCTs and was then diagnosed with primary central nervous system (PCNS) PTLD by brain biopsy. The third HSCT was a haplo-identical peripheral blood stem cell transplantation from his mother, with post-transplant high-dose cyclophosphamide and tacrolimus used as graft-versus-host disease prophylaxis. Four months after the HSCT, multiple small ring lesions were detected in the parabasal ganglia of the patient's brain during magnetic resonance imaging. A lesion biopsy indicated Epstein-Barr virus (EBV)-positive, diffuse large B-cell lymphoma. Because the patient had no evidence of systemic lymphadenopathy, we diagnosed him with PCNS-PTLD. There was no EBV DNA in this patient's cerebrospinal fluid. The diagnosis of PCNS-PTLD by EBV DNA polymerase chain reaction is difficult and highlights the importance of a brain biopsy to diagnose PCNS-PTLD, especially in cases showing no EBV DNA in the cerebrospinal fluid. Although a rare condition, it is essential to locate and analyze cases of PCNS-PTLD after HSCT to establish the optimal strategy for treatment or prophylaxis.

Iron removal enhances vitamin C-induced apoptosis and growth inhibition of K-562 leukemic cells.

Although vitamin C (VC) has recently garnered interest as an alternative cancer therapy, its clinical effects remain controversial. It was recently reported using in vitro prostate cancer cell lines that excess extracellular iron (EEI) diminishes anti-cancer effects of VC, promoting the decomposition of hydrogen peroxide (H2O2) generated by VC. Here we demonstrated that EEI diminished the inhibitory effect of VC on the survival of K562 human leukemic cells in vitro, by reducing the amount of H2O2 and abrogating the apoptosis pathways induced by VC. In vivo, in the presence of EEI, the growth inhibitory effect of VC on K562 cells was completely abrogated; in fact, VC enhanced K562 cell growth. Reduction of EEI restored the apoptosis-inducing effect of VC in vitro and enhanced the growth inhibitory effect of VC in vivo. Further studies are warranted to investigate whether the combination of VC and iron depletion has similar effects in various other leukemic or cancer cells against which VC has been effective in previous experimental studies.

Environmentally benign process for the preparation of antimicrobial α-methylene-ß-hydroxy-γ-butyrolactone (tulipalin B) from tulip biomass.

Tulipalin B (α-methylene-ß-hydroxy-γ-butyrolactone, PaB) is an antimicrobial natural product occurring in tulip (Tulipa gesneriana). PaB is directly formed from the precursor glucose ester 6-tuliposide B (PosB) by endogenous Pos-converting enzyme (TCE). Despite the potential usefulness of antibacterial PaB in various industrial applications, lack of facile synthetic schemes hampers its practical use. Herein, we describe an environmentally benign and facile process for the preparation of PaB using tulip biomass materials based on one-step enzyme reaction catalyzed by TCE without the use of petroleum-derived solvents. By screening 115 tulip cultivars, we found three elite cultivars, which accumulated PosB almost exclusively in flower tissues. The flower extracts with aqueous ethanol were partially purified with activated charcoal and subjected to the enzyme reaction with reusable immobilized TCE prepared from bulb crude extracts. The reaction was completed in a few hours at room temperature, and PaB was purified with activated charcoal and ethanol in a batch-wise manner.