Priapism as an initial manifestation in an adult patient with chronic myeloid leukemia in Japan: case report and review of the literature.

We report the first documented Japanese case in the English literature of chronic myeloid leukemia (CML) in which priapism was the presenting symptom. Priapism, a rare manifestation in CML patients, is particularly uncommon in Japan. This can be attributed to the high quality of medical services and proactive health strategies implemented by the Japanese government. These strategies include recommending regular blood tests for company employees aged 35 and above, thereby facilitating early detection of CML. Hence, it is crucial to consider CML when examining any patient presenting with priapism, particularly among those who have not undergone regular medical check-ups.

Isolation of OXA-48-like carbapenemase-producing Escherichia coli susceptible to piperacillin/tazobactam in a Japanese patient without a history of travel abroad.

Oxacillinase (OXA)-48-like ß-lactamases are the most common carbapenemases in Enterobacterales in certain regions of the world and are being introduced on a regular basis into regions of non-endemicity. Japan has been characterized by low rates of carbapenemase-producing Enterobacterales, and among them, OXA-48-like carbapenemase-producing isolates are extremely rare. Here we describe a Japanese medical worker, without a history of travel abroad, who was diagnosed as having a community-acquired urinary tract infection, and whose urine sample was found to be positive for OXA-48-like carbapenemase-producing Escherichia coli. None of her close contacts had a history of foreign travel, and the same drug-resistant organism was not observed in other patients who had been hospitalized and undergone environmental culture tests in the same medical institution. This isolate was resistant to penicillins, narrow-spectrum cephalosporins, fluoroquinolones, and cefmetazole, but was susceptible to broad-spectrum cephalosporins, piperacillin/tazobactam, and meropenem and displayed reduced susceptibility to imipenem. The modified carbapenem inactivation test supported carbapenemase production, but inhibitor-based synergistic tests yielded negative results of carbapenemase production. Multiplex polymerase chain reaction revealed the presence of the carbapenemase gene (blaOXA-48) blaTEM and AmpC ß-lactamase gene (blaDHA). Singleplex polymerase chain reaction targeting the blaOXA-48 region amplified a product sequencing to nearly the full length (722 bp) and matching 100% with OXA-48. The present case highlights a new concern regarding OXA-48-like carbapenemase-producing Enterobacterales, which remain challenging to detect for clinical laboratories in regions of non-endemicity, and may already be latent in Japan.

Presumptive complicating Clostridium paraputrificum bacteremia as a presenting manifestation in a patient with undiagnosed ulcerative colitis followed by acute colonic pseudo-obstruction.

Clostridium paraputrificum is a member of the commensal flora of the gastrointestinal tract and skin. Despite being linked with cases of severe invasive infection, this organism is an uncommon pathogen in humans. Here, we report a case of undiagnosed ulcerative colitis in which the presentation was one of presumptive complicating C. paraputrificum bacteremia and, later, acute colonic pseudo-obstruction. The patient was an elderly male with prostate cancer who was admitted in a state of shock secondary to suspected septicemia from an abdominal source. Only one of two sets of anaerobic blood cultures were positive for C. paraputrificum. Endoscopic and pathological investigations revealed proctitis consistent with ulcerative colitis. The patient's abdominal manifestations worsened, and abdominal imaging demonstrated de novo massive colonic dilatation without any apparent mechanical obstruction. We speculated that C. paraputrificum bacteremia caused by undiagnosed ulcerative colitis had created ideal conditions for acute colonic pseudo-obstruction. This case demonstrates that C. paraputrificum bacteremia can be associated with latent severe gastrointestinal pathologies, indicating the need to investigate any abdominal source of infection, even if only a single blood culture is positive.

A case of fatal myxedema coma with electrocardiogram Osborne J-wave in a patient initially diagnosed with hypothyroidism.

Myxedema coma is a life-threatening endocrine emergency with a high mortality rate resulting from severe insufficiency of thyroid hormones. Intravenous levothyroxine replacement is considered the standard therapy for myxedema coma in many countries. In Japan, however, although there are diagnostic criteria highly suggestive or diagnostic for myxedema coma, no management strategy has been established, despite the availability of levothyroxine. Here we report a 75-year-old man with a history of Alzheimer's disease and schizophrenia who developed somnolence and generalized edema. Except for a pulse rate of 60 bpm, his vital signs and blood oxygen level were stable. Thyroid studies showed an elevated serum thyrotropin level of 219.2 µU/mL and a decreased serum free-thyroxine level of 0.15 ng/dL. On this basis he was diagnosed as having hypothyroidism rather than being highly suggestive for myxedema coma. Daily oral levothyroxine 25 µg was initiated and increased to 50 µg 3 days later. Seven days after being started on levothyroxine, the patient suddenly developed impaired consciousness, hypoxemia, hypotension, hypothermia, and hyponatremia. Electrocardiography revealed junctional bradycardia with Osborne J-wave. Myxedema coma was therefore diagnosed. He went into cardiac arrest in the emergency room but was resuscitated. Despite subsequent intravenous administration of hydrocortisone and levothyroxine, as well as intensive supportive care, he eventually died 12 hours after hospital admission. This case illustrates some of the challenges associated with the management of patients with signs highly suggestive/diagnostic of myxedema coma, including the optimal loading dosage and intervention timing of thyroid hormone replacement.

Monitoring of MYD88 L265P mutation by droplet digital polymerase chain reaction for prediction of early relapse in a patient with Bing-Neel syndrome.

Bing-Neel syndrome (BNS) is a rare neurologic complication of lymphoplasmacytic lymphoma (LPL) characterized by direct infiltration of lymphoplasmacytic cells (LPCs). Although no standard treatment has yet been established, patients with BNS harboring the MYD88 L265P mutation have been reported to respond favorably to ibrutinib, which can cross the blood-brain barrier and trigger apoptosis of MYD88 L265P-positive LPCs. However, it is still unclear whether monitoring of MYD88 L265P mutation status would be useful for predicting relapse/progression or for assisting diagnosis and evaluating response to chemotherapy. Here, we report the case of a patient with BNS receiving ibrutinib in whom we detected relapse early by monitoring for molecular residual disease (MRD) based on the presence of the MYD88 L265P mutation in cerebrospinal fluid (CSF) on droplet digital polymerase chain reaction assay. Persistent MRD increased 2 weeks before the onset of relapse symptoms without any abnormal imaging findings or evidence of clonal LPCs on CSF cytology, flow cytometry analysis, or immunofixation electrophoresis. Our findings suggest that an increase in MRD levels is correlated with relapse in patients with BNS.

Occupational Lead Poisoning in a Patient with Acute Abdomen and Normocytic Anemia.

We herein report a 24-year-old male construction worker with occupational lead poisoning who presented with acute abdomen and normocytic anemia. The levels of urinary delta-aminolevulinic acid and free erythrocyte protoporphyrin were elevated without any increase in the level of urine porphobilinogen. Detection of an elevated blood lead level of 100 µg/dL confirmed a diagnosis of lead poisoning. Chelation therapy with calcium disodium ethylenediaminetetraacetate resulted in prompt improvement of the clinical symptoms and the blood lead level. Clinicians should be aware that lead poisoning caused by occupational exposure can still occur sporadically in construction workers in Japan.

Hemodialysis vascular access infection caused by Methylobacterium radiotolerans: The first confirmed case in Japan.

Methylobacterium species are heterotrophic and fastidious Gram-negative bacilli that can be opportunistic pathogens in immunocompromised patients. These species form pink-pigmented colonies on agar plates and have been frequently isolated from tap water in hospitals. Herein, we describe a case of vascular access-related bloodstream infection caused by Methylobacterium radiotolerans in an 82-year-old man who was undergoing hemodialysis and had an implanted permanent pacemaker. Gram-negative rods cultured from his peripheral blood after incubation for 7 days were identified as M. radiotolerans by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) and 16S rRNA gene sequencing. The patient was treated with meropenem and daptomycin for 8 days, and levofloxacin was subsequently given orally for 6 days. However, eleven days after completion of the treatment, the patient developed another febrile episode, and the vascular access line blood and his peripheral blood also grew M. radiotolerans. Meropenem and rifampicin were administered and the vascular access line was removed and replaced. Subsequently, oral levofloxacin and rifampicin treatment was maintained for 8 weeks and the patient recovered without removal of the permanent pacemaker. M. radiotolerans grew slowly in blood culture, and the isolate showed optimal growth on Reasoner's 2 Agar (R2A). To our knowledge, this is the first report of a hemodialysis vascular access-related bloodstream infection caused by M. radiotolerans in Japan. Our experience suggests that clinicians should be aware of the possibility of vascular access infection caused by M. radiotolerans.

A patient with severe fever with thrombocytopenia syndrome and hemophagocytic lymphohistiocytosis-associated involvement of the central nervous system.

Severe fever with thrombocytopenia syndrome (SFTS), a severe infectious disease caused by novel bunyavirus, SFTS virus (SFTSV), is endemic to China, Korea, and Japan. Most SFTS patients show abnormalities in consciousness. Pathological findings in the central nervous system (CNS) of SFTS patients are not reported. A 53-year-old Japanese man was admitted to Uwajima City Hospital with an 8-day history of fever and diarrhea. Laboratory tests revealed leukopenia, thrombocytopenia, and liver enzyme elevation. He was diagnosed as having severe fever with thrombocytopenia syndrome (SFTS) following detection of the SFTSV genome in his blood. Bone marrow aspiration revealed hemophagocytic lymphohistiocytosis. He suffered progressive CNS disturbance and died on day 13 from onset of first symptoms. The SFTSV genome load in blood and levels of certain cytokines increased over the disease course. Necrotizing lymphadenitis with systemic lymphoid tissues positive for nucleocapsid protein (NP) of SFTSV was revealed by immunohistochemical (IHC) analysis. SFTSV-NP-positive immunoblasts were detected in all organs examined, including the CNS, and in the vascular lumina of each organ. Parenchymal cells of all organs examined were negative for SFTSV-NP on IHC analysis. Microscopic examination of the pons showed focal neuronal cell degeneration with hemosiderin-laden macrophages around extended microvessels with perivascular inflammatory cell infiltration and intravascular fibrin deposition. Autopsy confirmed this patient with SFTS was positive for systemic hemophagocytic lymphohistiocytosis including in the CNS. This patient's neurological abnormalities may have been caused by both functional and organic abnormalities. These novel findings provide important insights into the pathophysiology of SFTS.

Unusual presentation of a severely ill patient having severe fever with thrombocytopenia syndrome: a case report.

BACKGROUND: Severe fever with thrombocytopenia syndrome is an emerging infectious disease caused by a novel phlebovirus belonging to the family Bunyaviridate. Emergence of encephalitis/encephalopathy during severe fever with thrombocytopenia syndrome progression has been identified as a major risk factor associated with a poor prognosis. Here we report the case of a severely ill patient with severe fever with thrombocytopenia syndrome virus-associated encephalitis/encephalopathy characterized by a lesion of the splenium, which resolved later. CASE PRESENTATION: A 56-year-old Japanese man presented with fever and diarrhea, followed by dysarthria. Diffusion-weighted magnetic resonance imaging demonstrated high signal intensity in the splenium of the corpus callosum. The severe fever with thrombocytopenia syndrome virus genome was detected in our patient's serum, and the clinical course was characterized by convulsion, stupor, and hemorrhagic manifestations, with disseminated intravascular coagulation and hemophagocytic lymphohistiocytosis. Supportive therapy not including administration of corticosteroids led to gradual improvement of the clinical and laboratory findings, and magnetic resonance imaging demonstrated resolution of the splenial lesion. The serum severe fever with thrombocytopenia syndrome viral copy number, which was determined with the quantitative reverse-transcription polymerase chain reaction, rapidly decreased despite the severe clinical course. Our patient's overall condition improved, allowing him to be eventually discharged. CONCLUSIONS: Patients with encephalitis/encephalopathy due to severe fever with thrombocytopenia syndrome virus infection may have a favorable outcome, even if they exhibit splenial lesions and a severe clinical course; monitoring the serum viral load may be of value for prediction of outcome and potentially enables the avoidance of corticosteroids to intentionally cause opportunistic infection.

Diffuse large B-cell lymphoma, not otherwise specified presenting with bone and bone marrow involvement in the absence of lymphadenopathy.

A 74-year-old woman visited our hospital because of right chest pain and fatigue. Laboratory examinations revealed pancytopenia and an elevated level of serum lactate dehydrogenase. Although bone lesions were detected by computed tomography, there was no lymphadenopathy. Blastoid cells were evident in the bone marrow. From the patient's medical history and results of immunohistological and chromosomal analysis, she was diagnosed as having diffuse large B-cell lymphoma, not otherwise specified. This form of presentation of diffuse large B-cell lymphoma is very rare, and emphasizes the need for careful evaluation of such cases, including bone marrow biopsy for accurate diagnosis.

Acute abdomen due to group A streptococcus bacteremia caused by an isolate with a mutation in the csrS gene.

Streptococcus pyogenes (group A streptococcus) is an aerobic gram-positive coccus that causes infections ranging from non-invasive pharyngitis to severely invasive necrotizing fasciitis. Mutations in csrS/csrR and rgg, negative regulator genes of group A streptococcus, are crucial factors in the pathogenesis of streptococcal toxic shock syndrome, which is a severe, invasive infection characterized by sudden onset of shock and multiorgan failure, resulting in a high mortality rate. Here we present a case of group A streptococcal bacteremia in a 28-year-old Japanese woman with no relevant previous medical history. The patient developed progressive abdominal symptoms that may have been due to spontaneous bacterial peritonitis, followed by a state of shock, which did not fulfill the proposed criteria for streptococcal toxic shock. The isolate was found to harbor a mutation in the negative regulator csrS gene, whereas the csrR and rgg genes were intact. It was noteworthy that this strain carrying a csrS mutation had caused group A streptococcal bacteremia characterized by acute abdomen as the presenting symptom in a young individual who had been previously healthy. This case indicates that group A streptococcus with csrS mutations has potential virulence factors that are associated with the onset of group A streptococcal bacteremia that does not meet the diagnostic criteria for streptococcal toxic shock syndrome.

[Diagnosis of disseminated bone marrow carcinomatosis from gastric carcinoma initially presenting as asymptomatic anemia].

A 75-year-old man who had undergone subtotal gastrectomy for advanced gastric cancer 18 years previously with no signs of recurrence visited our hospital because of anemia detected by medical examination. Although no clinical abnormalities were evident, treatment with iron and vitamin B12 was started. However, because serum ALP was elevated, metastatic bone cancer was suspected. Subsequently, upper gastrointestinal endoscopy revealed findings suggestive of residual gastric cancer, and examination of a biopsy specimen demonstrated signet ring cell carcinoma. Furthermore, cells in a bone marrow biopsy sample showed morphology similar to that of cells obtained by stomach biopsy. FDG-PET demonstrated FDG accumulation only in the bone and residual stomach. The final diagnosis was bone metastasis from residual gastric cancer, and disseminated carcinomatosis of the bone marrow. Thereafter, pancytopenia progressed rapidly, and the patient died due to disseminated intravascular coagulation. When serum ALP is elevated in patients with a history of gastric cancer, bone marrow carcinomatosis should be suspected irrespective of symptoms, and imaging studies and bone marrow examination should be performed.

Analysis of chemotherapy-induced neutropenia and optimal timing for prophylactic use of G-CSF in B-cell non-Hodgkin lymphoma patients treated with R-CHOP.

BACKGROUND: Febrile neutropenia (FN) is one of the serious complications of chemotherapy. However, the hematological nadir after chemotherapy and the timing of prophylaxis for FN remain unclear, especially for outpatients. METHODS: We prospectively analyzed laboratory data from outpatients treated with a single chemotherapy regimen, rituximab (R)-CHOP, on three consultation days (days 8, 10, and 15) after chemotherapy to identify any factors that might predict the onset of the hematological nadir and the optimal timing of G-CSF prophylaxis. RESULTS: A total of 100 courses of chemotherapy (total 33 patients) were analyzed. Onset of the hematological nadir was not predictable in any of the patients who had a white blood cell count (WBC) of >5,500 × 10(6)/L and/or monocyte count of >80 × 10(6)/L on day 8, and thus there was little opportunity for G-CSF prophylaxis in each treatment course. Among patients who had a WBC count of 1,500-5,500 × 10(6)/L on day 8, the monocyte count on day 8 was significantly associated with the hematological nadir. Patients who had a monocyte count of <5 × 10(6)/L on day 8, were identified as a high-risk group for neutropenia for whom G-CSF administration during the current treatment course should be considered. CONCLUSION: Our results indicate that, in outpatients receiving R-CHOP chemotherapy, the monocyte count on day 8 is a useful marker of the hematological nadir, allowing an opportunity for G-CSF prophylaxis.

Role of activation-induced cytidine deaminase in the progression of follicular lymphoma.

Activation-induced cytidine deaminase (AID/AICDA) is required for somatic hypermutation and class-switch recombination of the immunoglobulin gene, and for c-myc translocation of germinal center-derived B-cell lymphoma. In the present study, we attempted to clarify the significance of AID associated with c-myc in the progression of follicular lymphoma (FL) using RT-PCR and quantitative real-time PCR. Tissues from the patients with grade 3 FL expressed relatively higher levels of c-myc and AID. The samples taken from a patient with FL who died within 2 years after the start of treatment showed either no or low expression of AID, despite expressing high levels of c-myc. In order to examine the role of AID expression in rapidly progressive FL, the full-length AID transcript was transfected into AID-negative cell lines established from different patients with rapidly progressive FL. This led to the establishment of AID-expressing transfectants with a low proliferation rate and a significantly increased incidence of G(0)/G(1) arrest compared with controls. Our results indicate that AID may act as a negative regulator of cell survival in FL when sufficient c-myc is expressed. Switch-off or low expression of AID after c-myc amplification may correlate with the clinical outcomes of FL.

Usage of granulocyte colony-stimulating factor every 2 days is clinically useful and cost-effective for febrile neutropenia during early courses of chemotherapy.

BACKGROUND: In order to analyze the clinical activity and cost-effectiveness of granulocyte colony-stimulating factors (G-CSF), the prophylactic usage of G-CSF in patients treated with a single chemotherapy regimen during early courses was prospectively evaluated. METHODS: Thirty patients with newly diagnosed non-Hodgkin lymphoma (NHL) treated with the first course of an R-CHOP regimen were enrolled randomly. After treatment with the first course of chemotherapy, a daily dose of G-CSF (lenograstim, 100 µg) was administered to half (15 cases) of the patients, and a dose of G-CSF (100 µg) was administered every other day to the other half of the patients when leukocytopenia (<1.5 × 10(9)/L) and/or neutropenia (<0.5 × 10(9)/L) occurred. Changes in leukocyte and neutrophil counts, prophylaxis, febrile neutropenia (FN) events, and cost performance between the two groups were analyzed. RESULTS: No significant difference between the two groups was observed in recoveries of leukocyte and neutrophil counts and evidence of FN. The only difference was the total cost of G-CSF. CONCLUSION: We concluded that every-other-day use of G-CSF was as clinically effective for the prophylaxis of FN as the daily use of G-CSF, and economically speaking, the administration of G-CSF every other day should be more beneficial for patients with NHL during early courses of R-CHOP chemotherapy.

Myeloid sarcoma in essential thrombocythemia that transformed into acute myeloid leukemia.

A 72-year-old man was diagnosed with essential thrombocythemia (ET) and was treated with hydroxyurea for approximately 5 years. He was well until April 2007. In May 2007, a slight fall in hemoglobin levels was found. In June 2007, an upper endoscopy performed to investigate the cause of anemia showed multiple polypoid lesions in the body of the stomach. A gastric biopsy showed a diffuse infiltration of very immature cells. Several additional immunohistochemical staining showed that the cells were positive for CD13, CD34, CD117, and HLA DR, but negative for myeloperoxidase, CD42b, glycophorin, B cell marker, T cell marker, cytokeratin and desmin. We finally diagnosed the condition as myeloid sarcoma. Subsequently, the patient's ET transformed into acute myeloid leukemia. To our knowledge, this is an exceedingly rare event involving a patient with essential thrombocythemia.

Follicular dendritic cell tumor as an unknown primary tumor.

A 70-year-old Japanese man presented to our hospital with a 1-month history of progressive general fatigue and anorexia. A physical examination revealed severe anemic condition, mild persistent splenomegaly, and no palpable surface lymph nodes. He had pleural effusion and ascites, though no malignant cells were detected in the effusion. He eventually died without any diagnosis of his disease. Immunohistochemical staining of his tumor after autopsy showed atypical cells that were negative for epithelial membrane antigen (EMA), keratin (AE1/3), keratin-20, vimentin, factor VIII, leukocyte common antigen (LCA/T200; CD45), myeloperoxidase (MPO), terminal deoxynucleotidyl transferase (TdT), lysozyme, CD1a, CD3, CD4, CD10, CD15, CD20 (L26), CD21, CD23, CD34, CD43, CD56, CD68, CD79a, CD138, and EBER-1 in situ. Only a few scattered cells expressed CD30, but they showed no staining for anaplastic large-cell lymphoma kinase (ALK). A few scattered cells expressed S-100 antigen and the majority of cells dominantly expressed dendritic cell-associated antigens (CD35, FDC, Ki-M1p). In conclusion, we found this unknown primary tumor to be consistent with a follicular dendritic cell tumor with anaplastic features.

[Two cases of heparin-induced thrombocytopenia (HIT) and a review of the literature].

We experienced two cases of heparin-induced thrombocytopenia (HIT) which occurred during unfractionated heparin treatment. The first patient was a 72-year-old man, who was admitted to our hospital because of sudden onset dyspnea in January 2000. He was diagnosed as having a pulmonary embolism and heparin was started. Nine days later, progressive embolization of the pulmonary artery and femoral vein was found and thrombocytopenia (platelet count 20 x 10(9)/l) was observed 14 days after that. Cessation of heparin and administration of argatroban resulted in progressive normalization of the platelet count. The second patient was a 62-year-old woman, who was admitted to our hospital in April 2001, with the chief complaint of sudden onset dyspnea. She was diagnosed as having acute left-sided heart failure and heparin was started. Fifteen 15 days later, thrombocytopenia (platelet count 17 x 10(9)/l) was observed. Cessation of heparin resulted in normalization of the platelet count. Both cases were positive for anti-heparin-platelet factor 4 (PF4) antibody. Here we report on the clinical course of two cases of HIT with a review of the literature.