Recurrent bilateral adrenal infarction with myelodysplastic/myeloproliferative neoplasm-unclassifiable (MDS/MPN-U): a case report.

BACKGROUND: Bilateral adrenal infarction is rare and only a small number of cases have been reported so far. Adrenal infarction is usually caused by thrombophilia or a hypercoagulable state, such as antiphospholipid antibody syndrome, pregnancy, and coronavirus disease 2019. However, adrenal infarction with myelodysplastic/myeloproliferative neoplasm (MDS/MPN) has not been reported. CASE PRESENTATION: An 81-year-old man with a sudden severe bilateral backache presented to our hospital. Contrast-enhanced computed tomography (CT) led to the diagnosis of bilateral adrenal infarction. Previously reported causes of adrenal infarction were all excluded and a diagnosis of MDS/MPN-unclassifiable (MDS/MPN-U) was reached, which was considered to be attributed to adrenal infarction. He developed a relapse of bilateral adrenal infarction, and aspirin administration was initiated. Partial primary adrenal insufficiency was suspected as the serum adrenocorticotropic hormone level was persistently high after the second bilateral adrenal infarction. CONCLUSION: This is the first case of bilateral adrenal infarction with MDS/MPN-U encountered. MDS/MPN has the clinical characteristics of MPN. It is reasonable to assume that MDS/MPN-U may have influenced bilateral adrenal infarction development, considering the absence of thrombosis history and a current comorbid hypercoagulable disease. This is also the first case of recurrent bilateral adrenal infarction. It is important to carefully investigate the underlying cause of adrenal infarction once adrenal infarction is diagnosed, as well as to assess adrenocortical function.

Toxic shock like syndrome caused by Streptococcus agalactiae bacteremia during treatment for multiple myeloma.

Toxic shock-like syndrome (TSLS) is a life-threatening hyperinflammatory complication caused by Streptococcus species infections. We reported the first case of TSLS caused by primary bacteremia of Streptococcus agalactiae during chemotherapy for multiple myeloma. A 74-year-old woman, who received combination chemotherapy of elotuzumab, pomalidomide, and dexamethasone for treatment-refractory multiple myeloma, was transported to our hospital under comatose and septic shock. Her blood culture detected Streptococcus agalactiae, and considering the progressive multiorgan failure, she was diagnosed with TSLS. Empiric antibiotic treatment with meropenem and respiratory and circulatory support were quickly initiated, resulting in an almost complete recovery of organ functions. It should be noted that with the advances of chemotherapy, the risk of infection is becoming more diverse.

Successful treatment of pneumonia caused by multidrug-resistant Pseudomonas aeruginosa after allogeneic hematopoietic stem cell transplantation with colistin and amikacin inhalation therapy.

Pseudomonas aeruginosa is a Gram-negative bacillus that often causes severe infections during immunosuppression in patients with hematologic malignancies. P. aeruginosa can easily acquire drug resistance, and often develops into multidrug-resistant P. aeruginosa (MDRP). Although many antibiotics are used in combination to treat MDRP infections, colistin and amikacin are less likely to be transferred to the lungs, and inhalation therapy may be used. Herein, we report a Case of pneumonia caused by MDRP after allogeneic hematopoietic stem cell transplantation (HSCT) treated with inhaled colistin and amikacin. This 61-year-old female patient was diagnosed with myelodysplastic syndromes and underwent allogeneic HSCT from an 8/8 HLA-matched unrelated donor after reduced-intensity conditioning. On the day of the stem cell infusion, the patient's sputum culture was found to be positive for MDRP. The patient subsequently developed bacteremia, pneumonia, and lung abscess caused by MDRP, and we administered multidrug antibiotic therapy including colistin and amikacin inhalation therapy. The patient's blood cultures were subsequently turned negative, and the lung abscess disappeared. To our knowledge, this is the first case of MDRP pneumonia after HSCT in which colistin and amikacin inhalation therapy was effective.

Cerebral toxoplasmosis complicating lymphoplasmacytic lymphoma in partial remission.

Toxoplasma gondii can develop toxoplasmic encephalitis (TE) in immunodeficient conditions such as AIDS and after organ transplantation. While some cases of TE with malignant lymphoma were reported, these cases occurred immediately after chemotherapy or when their diseases were active. Here we report the first Case of TE that occurred in patient who was in partial remission (PR) of lymphoplasmacytic lymphoma (LPL) for two years. A 76-year-old man was referred to our institute because of disturbance of consciousness, right arm weakness and paresthesia. A computed tomography (CT) scan detected multiple nodules in his brain. Magnetic resonance imaging (MRI) of the head detected multiple gadolinium-enhancing parenchymal lesions with hyperintense signals on T2-and diffusion-weighted images, located in both cerebral and cerebellar hemispheres. Blood test and cerebrospinal fluid (CSF) findings were unremarkable. His rapidly deteriorating consciousness precluded a chance of brain biopsy. Considering the limited efficacy of antimicrobials and the imaging findings that could be compatible with the diagnosis of malignant lymphoma, we suspected central nerve system (CNS) recurrence of LPL. Although chemotherapy was initiated, he died of respiratory failure just after chemotherapy. A pathological autopsy showed his cause of death was TE. To our knowledge, this is the first case of TE in long-term PR of malignant lymphoma. TE should be suspected when patients with malignant lymphoma present unexplained neurologic symptoms regardless of their treatment efficacy of lymphoma. (226/250 words).

Severe cellulitis caused by Achromobacter xylosoxidans after allogeneic hematopoietic stem cell transplantation.

Achromobacter xylosoxidans (A. xylosoxidans) is an aerobic gram-negative bacillus and often isolated from aquatic environments. It is supposed to cause infections in patients with malignancy or immunodeficiency. It causes various healthcare-associated infections, but cellulitis is rare. Herein, we report the first case of sever cellulitis by A. xylosoxidans after allogeneic hematopoietic stem cell transplantation (HSCT). A 49-year-old man underwent allogeneic HSCT from 8/8 HLA-matched unrelated donor with myeloablative conditioning for relapsed acute myeloid leukemia. He developed skin chronic graft versus host disease 11 months after HSCT. During the prolonged treatment with prednisolone and cyclosporine, he developed cellulitis on his left leg and admitted to our hospital. Blood and exudate culture revealed A. xylosoxidans. Although empirical therapy with cefepime was ineffective, his symptoms were dramatically improved after administration of meropenem. To our knowledge, this is the first case of A. xylosoxidans cellulitis after allogeneic HSCT. A. xylosoxidans should be considered as a possible cause of cellulitis in post-allogeneic HSCT patients on prolonged immunosuppressive therapy.

TUBB1 dysfunction in inherited thrombocytopenia causes genome instability.

Inherited thrombocytopenia is a genetically heterogeneous disease characterized by varying degrees of thrombocytopenia and risk of haematological malignancy, and the genetic cause of many cases remains unknown. We performed whole-exome sequencing of a family with thrombocytopenia and myeloid malignancy and identified a novel TUBB1 variant, T149P. Screening of other thrombocytopenia pedigrees identified another TUBB1 variant, R251H. TUBB1 encodes the tubulin ß-1 chain, a major component of microtubules abundant in megakaryocytes. Variant TUBB1 disrupted the normal assembly of microtubules and impaired proplatelet formation in vitro. In addition, DNA damage response was severely attenuated by loss of TUBB1. We found that the nuclear accumulation of p53 (also termed TP53) and the expression of pro-apoptotic genes triggered by genotoxic stress were blocked in TUBB1-deficient cells and, accordingly, apoptosis after DNA damage was diminished by knockdown of TUBB1. Thus, we have demonstrated that microtubule dysfunction confers resistance to apoptosis, even in DNA damage-accumulated cells, which explains genome instability in the affected individuals. These studies will lead us to a better understanding of how microtubule dysfunction can contribute to the accumulation of DNA damage, genetic instability and leukaemogenesis.

Effect of Using a Cardiac Catheterization Table-Stabilizing Stick on the Quality of Cardiopulmonary Resuscitation in the Cardiac Catheterization Laboratory: A Simulation-Based Study.

Rapid defibrillation and high-quality cardiopulmonary resuscitation (CPR) are necessary for patients with cardiopulmonary arrest, one of the most serious and frequently encountered complications in cardiac catheterization laboratories. However, when the catheterization table is withdrawn from its neutral position for fluoroscopy, it is unstable and unsuitable for resuscitation because of its cantilever structure. To stabilize the table in its withdrawn position, the use of a table-stabilizing stick might improve CPR quality. To investigate the effect of using a cardiac catheterization table-stabilizing stick on CPR quality, a CPR simulation mannequin was placed on a cardiac catheterization table that was withdrawn from the C-arm of the X-ray machine. CPR quality was assessed with or without the use of a table-stabilizing stick under the table. The CPR quality assessment (Q-CPR) scores were 79.6 ± 11.4% using the table-stabilizing stick and 47.7 ± 30.3% without the use of the stick device (p = 0.02). In this simulation-based study, the use of a table-stabilizing stick in a cardiac catheterization table withdrawn from the C-arm of the X-ray machine improved the quality of CPR.

[Development of Animation Projector System and Usefulness in Pediatric Head CT].

The restlessness of young children often causes motion artifacts on CT images. We devised a new animation projector system (CT Theater) that enables a child to view an animation during a pediatric head CT examination. The purpose of this study is to assess the usefulness on a children of a video viewed during a head CT scan. Children of 3-10 years old who underwent head CT (SOMATOM Definition Flash, SOMATOM Force; Siemens) were analyzed for a period from 6 months before, to 6 months after, introduction of the projector system (before: n=46, after: n=29). Mobile projector (MP-CL1; Sony) connected with tablet device (iPad; Apple) was put on the CT table near the child's head. An animation was projected on the child's line of sight inside the gantry. The animation is projected on the line of sight of the child such that the projector moves with the child on the table. The number of requests for use made by children was 28/29 (96.6%). The presence of images without motion artifacts decreased significantly after introduction (before/after introduction: 84.8% vs 100%, p=0.03). The overall examination success rate tended to increase after introduction (84.8% vs 92.9%, p=0.26). The overall examination time was significantly reduced (92.4±42.4 s vs 65.1±47.3 s, p<0.001). We developed an animation projector system that shortened examination time and decreased motion artifacts in pediatric head CT.

[Development of estimated time of arrival method and usefulness in pulmonary artery/vein separation 3D-CT].

We have developed an estimated time of arrival (ETA) method as a new single-phase scan for pulmonary artery/vein separation. This method enables differentiation of CT values between arteries and veins by means of two-step consecutive injection of contrast medium based on the pulmonary circulation time. This paper presents an overview of the ETA method and scan technique. Since the ETA method is a single-phase scan, it uses a low radiation dose compared with the conventional multi-phase scan. Moreover, this method eliminates gaps due to breath holding. The ETA method can detect irregularities and obtain high-quality pulmonary artery/vein separation 3D-CT images.

Primary Extranodal Diffuse Large B-cell Lymphoma Presenting in the Lips: A Case Report and Literature Review.

Approximately 30-40% of malignant lymphomas are classified as diffuse large B-cell lymphoma (DLBCL), with 30% of DLBCL cases manifesting as extranodal lymphomas. Among these extranodal DLBCLs, primary DLBCL in oral lesions, particularly in the lips, is rare. While the treatment methods, chemotherapy assessment, and prognosis for nodal and extranodal DLBCLs are generally similar, diagnostic challenges can lead to delayed therapeutic intervention. We herein present a recent case of primary extranodal DLBCL in the lips that was swiftly diagnosed and managed using rituximab-containing chemotherapies. Our experience underscores the important role that hematologists play in identifying the possibility of oral hematological tumors, thereby allowing for a rapid diagnosis and timely intervention.

Longitudinal CT, MRI, and 18F-FDG PET/CT Imaging Findings of Peliosis Hepatis: A Case Report.

Peliosis hepatis (PH) is a rare benign vascular condition characterized by sinusoidal dilatation and the presence of blood-filled spaces within the liver. PH is often clinically asymptomatic and is discovered incidentally. It presents a clinical challenge as its imaging findings frequently mimic other pathologies, including primary or secondary malignancies and abscesses. In this article, we present a case of a 73-year-old woman with a history of recurrent tongue cancer treated by surgery and chemoradiotherapy, and concurrent multiple myeloma, in whom PH was incidentally discovered. Based on computed tomography, magnetic resonance imaging, and 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) imaging findings prior to biopsy, PH was diagnosed, and pathologically confirmed. Follow-up computed tomography five months after the discontinuation of raloxifene hydrochloride, a selective estrogen receptor modulator and a suspected drug causing PH, the regression of PH lesions was observed.

Daratumumab plus lenalidomide and dexamethasone for relapsed POEMS syndrome with bone plasmacytoma harboring 17p deletion.

The standard therapies for polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes (POEMS) syndrome are radiation therapy, high-dose chemotherapy followed by autologous stem cell transplantation, and lenalidomide combined with dexamethasone. Daratumumab was reported to be effective for treatment-naive and relapsed POEMS syndrome, but treatment options for relapsed POEMS syndrome with poor prognostic factors or cytogenetic abnormalities have not been established due to a lack of studies in these patients. Here, we describe a case of relapsed POEMS syndrome with bone plasmacytoma harboring a newly detected 17p deletion after high-dose chemotherapy followed by autologous stem cell transplantation and radiation therapy in a male patient. He was successfully treated with daratumumab plus lenalidomide and dexamethasone (Dara-Rd). Dara-Rd could be effective in relapsed POEMS syndrome with 17p deletion, which is known as a poor cytogenetic abnormality in multiple myeloma. This report may broaden the application of Dara-Rd for POEMS syndrome.

Prompt Initiation of Conventional Chemotherapy to Avoid Early Death in Patients with Newly Diagnosed Acute Promyelocytic Leukemia.

Objective Compared to prospective trials, the early death rate of newly diagnosed acute promyelocytic leukemia (APL) in the real-world clinical setting is higher. However, the early death rate was heterogeneous according to the reported institutes. Thus, the therapeutic approach at each institute may be important for preventing early death. This study evaluated the management strategy for untreated APL in our institute to avoid early death. Methods We identified consecutive 21 patients with untreated APL who received induction therapy including all-trans retinoic acid (ATRA) between July 2007 and December 2021 at the University of Tokyo Hospital. Results As therapeutic approaches, 16 patients (76%) received ATRA administration on the day of admission, and the remaining 5 received ATRA within 4 days from admission. Notably, all patients received conventional chemotherapy added to ATRA at a median of 1 day from admission (range: 0-9 days). As clinical outcomes, no patient died during induction therapy for untreated APL, and all achieved complete molecular remission. Conclusion Compared to the previous nationwide survey, a higher proportion of patients at our institute received conventional chemotherapy in addition to ATRA, and it was initiated more promptly, which may have helped prevent early death.

Acalabrutinib and steroid for autoimmune thrombocytopenia due to relapsed chronic lymphocytic leukemia with severe bone marrow infiltration.

Thrombocytopenia is a frequent complication in chronic lymphocytic leukemia (CLL). Differentiating autoimmune thrombocytopenia from thrombocytopenia due to bone marrow infiltration is necessary for appropriate treatment, but sometimes difficult. Here we report a 60-year-old male patient with CLL who had achieved complete response after treatment with fludarabine, cyclophosphamide, and rituximab two years prior to presentation. He was admitted with severe thrombocytopenia that was unresponsive to intravenous immunoglobulin. Imaging studies revealed systemic enlarged lymph nodes and bone marrow aspiration was hypercellular with > 95% lymphocytes and scant megakaryocytes. Acalabrutinib 200 mg/day was administered for the treatment of CLL exacerbation. A gradual decrease in CLL cells and recovery of megakaryocytes in bone marrow were observed, but platelet counts remained low. Systemic administration of prednisolone 0.5 mg/kg, in addition to acalabrutinib, was started, considering the contribution of autoimmune thrombocytopenia; platelet recovery was rapid and sustained for more than a year. Even if bone marrow examination suggested thrombocytopenia due to direct leukemic infiltration, it is difficult to exclude the possibility of concomitant immunogenic thrombocytopenia. We conclude that for CLL patients with severe thrombocytopenia, repeating bone marrow examination and concurrent immunosuppressive therapies and treatment of the underlying CLL may be beneficial.

Clinical characteristics of steroid-responsive but dependent chronic graft-versus-host disease: a multicenter retrospective analysis.

Chronic graft-versus-host disease (cGVHD) is a long-term complication of allogeneic hematopoietic stem cell transplantation. The clinical importance of long-term corticosteroid dependency in steroid-responsive cGVHD is undetermined. We retrospectively reviewed the data of 120 consecutive patients who received systemic steroid therapy for cGVHD between January 2007 and December 2018 at three institutions. Among patients with steroid-responsive cGVHD, those who successfully tapered off corticosteroids within 1 year were defined as the early withdrawal group (EW-cGVHD) and others were defined as the dependent group (Dp-cGVHD). Twenty-six patients were classified as EW-cGVHD and 55 as Dp-cGVHD. The proportion of men was significantly higher and performance status was significantly better in EW-cGVHD. The 5-year overall survival and cGVHD recurrence-free survival rates were significantly higher in EW-cGVHD than Dp-cGVHD (96% vs. 68%, p = 0.017 and 84% vs. 41%, p = 0.002, respectively). While the relapse-free survival rate did not differ significantly (84% vs. 65%, p = 0.15), the proportion of patients requiring readmission, mainly due to cGVHD recurrence or infection, was significantly increased in Dp-cGVHD (38% vs. 84%, p < 0.001). In summary, steroid dependency in cGVHD for more than 1 year was significantly associated with poor transplant outcomes.