Survey of sensory impairment in critically ill patients after intensive care unit discharge: An ambidirectional cohort study.

BACKGROUND: Sensory impairment affects the quality of life after intensive care. However, no studies have comprehensively examined sensory impairment after intensive care. OBJECTIVES: This study aimed to investigate sensory impairment in critically ill patients. METHODS: This ambidirectional cohort study was conducted in the intensive care unit (ICU) of a university hospital between April 2017 and January 2020. Patients who survived despite invasive mechanical ventilation for >48 h, with a discharge period of >6 months, participated in the study. A questionnaire was sent to consenting patients to investigate the presence or absence of sensory impairment at that time, and treatment-related data were collected from their medical records. RESULTS: Of 75 eligible patients, 62 responded to our survey. Twenty-seven (43.6%) patients had some sensory impairment. Nine (14.5%) patients had chronic pain after ICU discharge, 4 (6.5%) had chronic pain and visual impairment, 3 (4.8%) had visual impairment only, and 3 (4.8%) had chronic pain and taste impairment. The most common overlapping symptom was a combination of chronic pain. CONCLUSIONS: Critically ill patients who survived and were discharged from the ICU accounted for 43.6% of patients with complaints of sensory impairment in the chronic phase. The results of this study suggest the need for follow-up and treatment of possible sensory impairment following ICU discharge.

Impact of MRD on clinical outcomes of unrelated hematopoietic stem cell transplantation in patients with Ph+ ALL: A retrospective nationwide study.

Measurable residual disease (MRD) status before transplantation has been shown to be a strong prognostic factor in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). However, the outcomes of unrelated hematopoietic stem cell transplantation based on the MRD status have not been fully investigated. In this retrospective study, we compared the outcomes of 715 consecutive adults with Ph+ ALL in complete remission who underwent unrelated cord blood transplantation (UCBT) (single-unit UCBT, n = 232 [4/6, 5/6, and 6/6 HLA match]), HLA-matched unrelated bone marrow transplantation (UBMT; n = 292 [8/8 HLA match]), or HLA-mismatched UBMT (n = 191 [7/8 HLA match]). In the MRD+ cohort, adjusted 3-year leukemia-free survival rates were 59.8%, 38.3%, and 55.5% after UCBT, HLA-matched UBMT, and HLA-mismatched UBMT, respectively. In the MRD- cohort, the corresponding rates were 65.3%, 70.4%, and 69.7%, respectively. The MRD+ HLA-matched UBMT group had a significantly higher risk of relapse than the MRD+ HLA-mismatched UBMT group (hazard ratio [HR] in the MRD+ HLA-mismatched UBMT group, 0.33; 95% confidence interval [CI] 0.15-0.74) and the MRD+ UCBT group (HR in the MRD+ UCBT group, 0.38; 95% CI 0.18-0.83). Furthermore, HLA-matched UBMT had a significant effect of MRD on death (HR 1.87; 95% CI 1.19-2.94), relapse or death (HR 2.24; 95% CI 1.50-3.34), and relapse (HR 3.12; 95% CI 1.75-5.57), while UCBT and HLA-mismatched UBMT did not. In conclusion, our data indicate Ph+ ALL patients with positive MRD may benefit from undergoing UCBT or HLA-mismatched UBMT instead of HLA-matched UBMT to reduce leukemic relapse.

[Philadelphia chromosome-positive acute lymphoblastic leukemia complicated by concomitant Achromobacter xylosoxidans and Corynebacterium striatum bacteremia following allogeneic hematopoietic stem cell transplantation].

A 54-year-old woman with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) underwent hematopoietic stem cell transplantation from an HLA-matched sibling. Subsequently, she suffered from chronic graft versus host disease (GvHD) and received medical treatment. Fever developed on day 697 and resulted in a shock state at 10 h after the visit. Achromobacter xylosoxidans was detected in the initial blood culture on day 699. General conditions exacerbated even after the start of meropenem hydrate (MEPM, Meropen®) administration, with Corynebacterium striatum detected as an additional species in the initial blood culture on day 701. Although vancomycin hydrochloride (VCM, Vancomycin®) was administered, the conditions did not improve. She died on day 702. Between January 2012 and December 2016, A. xylosoxidans was detected only in nine cases in our hospital, which included five with hematological malignancies and only one (present) with sepsis. At the same time, Corynebacterium species were detected in blood cultures from 39 cases in our hospital, which included 31 with hematological malignancies. Some reports on drug-resistant A. xylosoxidans and C. striatum have been published. Infections with these species may become fatal when complicated by sepsis in immunocompromised patients with hematological malignancies. More cases should be accumulated for detailed investigation.

Post-allogeneic stem cell transplant extramedullary relapse of acute megakaryoblastic leukemia initially detected by elevated WT1 mRNA levels in peripheral blood.

An 18-year-old male was admitted to our hospital for fever, and was diagnosed with acute megakaryoblastic leukemia (AML M7) based on the presence of CD42a and CD61 positive myeloblasts in peripheral blood (PB). Induction chemotherapy at our hospital resulted in complete remission (CR). Subsequently, he underwent unrelated HLA-DR one locus-mismatched allogeneic bone marrow (BM) transplantation. Although CR was maintained without development of graft-versus-host disease (GvHD), the WT1 mRNA level in PB was elevated on post-transplant day 134. As BM aspiration performed 1 week later confirmed maintenance of CR, and because the WT1 mRNA level in BM was not high in comparison with PB, we suspected extramedullary relapse. PET-CT demonstrated a thymic tumor and a gastric tumor with abnormal accumulation of FDG, and biopsy confirmed both to be extramedullary relapse of AML M7. Induction chemotherapy following local radiation therapy achieved a second CR, following which he received HLA haploidentical peripheral blood stem cell transplantation on day 256 after the first transplant. The patient is currently surviving free from both relapse and GvHD. High WT1 mRNA levels in PB as compared with BM should raise suspicion of extramedullary relapse, and PET-CT is very useful for whole body evaluation in such cases.

Assessment of Dyspnea in Critically Ill Patients: A Comparative Analysis of Evaluation Scales.

Purpose This study aimed to evaluate the Respiratory Distress Observation Scale (RDOS), Intensive Care RDOS (IC-RDOS), and Mechanical Ventilation RDOS (MV-RDOS) as potential markers of dyspnea in ICU patients by describing their relationship with the Dyspnea Visual Analog Scale (D-VAS). Materials and methods A researcher and a trained nurse independently assessed ICU patients simultaneously. One researcher assessed the RDOS (IC/MV-RDOS) and the depth of sedation. An objective evaluation using the observational D-VAS was simultaneously performed by a trained nurse. Results The correlation coefficients for each scale were 0.338 for the D-VAS and RDOS, 0.239 for the IC-RDOS, and 0.237 for the MV-RDOS, indicating a low correlation. The prediction of self-reported dyspnea showed that each scale's area under the curve (AUC) as a predictor of D-VAS ≥4 was 0.79 (95% Confidence Interval [CI] 0.71-0.87) for RDOS, 0.77 (95% CI 0.68-0.84) for IC-RDOS, and 0.73 (95% CI 0.64-0.81) for MV-RDOS. Conclusions The objective rating scales RDOS, IC-RDOS, and MV-RDOS can predict subjective dyspnea to a certain extent; however, they have limitations in accurately discriminating dyspnea intensity.

Bosutinib-induced osteonecrosis of the jaw in a patient with chronic myeloid leukemia: a case report.

Medication-related osteonecrosis of the jaw (MRONJ) is an uncommon adverse drug reaction that can be induced by certain therapeutic drugs, including antiresorptive and antiangiogenic agents. Here, we describe the first case of ONJ induced by bosutinib, a tyrosine kinase inhibitor, in a patient with chronic myeloid leukemia (CML) who was not taking an antiresorptive agent. A 65-year-old male with no history of either antiresorptive treatment or dental surgery but diagnosed with CML had been undergoing treatment with bosutinib for 2 years. He developed right mandibular stage 2 osteonecrosis. The patient eventually underwent extensive surgery consisting of removal of the necrotic bone and infected soft tissue in combination with nasolabial flap reconstruction. He obtained complete resolution of MRONJ at 12 months postoperatively. As new cancer therapies become available, it is important that clinicians are aware of this novel case of bosutinib-induced ONJ in a patient undergoing CML treatment.

Efficacy and safety of quizartinib in Japanese patients with FLT3-ITD positive relapsed or refractory acute myeloid leukemia in an open-label, phase 2 study.

FMS-like tyrosine kinase 3 (FLT3) internal tandem duplication (ITD) mutations in patients with acute myeloid leukemia (AML) are associated with early relapse and poor survival. This multicenter, single-arm, two-stage phase 2 study (NCT02984995) was conducted to evaluate the efficacy and safety of quizartinib hydrochloride (initial dose 20/30 mg/day), an oral, highly potent, selective FLT3 inhibitor in Japanese patients (median age 65 years) with FLT3-ITD positive relapsed/refractory (R/R) AML. The composite complete remission (CRc) rate (primary endpoint) was 53.8% (90% confidence interval 36.2-70.8%) for evaluable patients in the efficacy analysis set. The median duration of CRc and overall survival was 16.1 weeks and 34.1 weeks, respectively. The most frequent treatment-emergent adverse events (TEAEs) were febrile neutropenia (43.2%), platelet count decreased (37.8%), and QT prolonged (35.1%). Two (5.4%) patients experienced TEAEs associated with treatment discontinuation. All serious TEAEs (45.9%), except febrile neutropenia (16.2%), were reported in ≤ 2 patients. The incidence of QTcF 451-480 ms and 481-500 ms was 37.8% and 2.7%, respectively. No QTcF > 500 ms, events of torsade de pointes or arrhythmia with clinical symptoms were reported. Quizartinib monotherapy was well tolerated and resulted in clinically meaningful reductions in blast count in Japanese patients with FLT3-ITD R/R AML.

Successful haploidentical stem cell transplantation with prophylactic administration of liposomal amphotericin B after invasive pulmonary zygomycosis.

A 54-year-old woman with acute myeloid leukemia (AML) achieved complete remission by induction chemotherapy, but developed zygomycosis after consolidation therapy. As zygomycosis could not be cured by liposomal amphotericin B and micafungin, left lower lobectomy was performed. As AML relapsed 7 months after onset, she received haploidentical stem cell transplantation under administration of liposomal amphotericin B. Despite experiencing severe acute graft-versus-host disease, she remains alive with no relapse of either zygomycosis or AML.