Characteristics and outcomes for pulmonary aspergillosis in critically ill patients without influenza: A 3-year retrospective study.

BACKGROUND: Previous studies have revealed higher mortality rates in patients of severe influenza coinfected with invasive pulmonary aspergillosis (IPA) than in those without the coinfection; nonetheless, the clinical outcome of IPA in critically ill patients without influenza remains unclear. PATIENTS AND METHODS: This retrospective study was conducted in three institutes. From 2016-2018, all adult patients diagnosed with IPA in the intensive care units (ICUs) were identified. The logistic regression was used to identify the potential risk factors associated with in-hospital mortality in patients with non-influenza IPA. The stratified analysis of IPA patients with and without antifungal therapy was also performed. The final model was established using a forward approach, selecting variables with p-values less than 0.05. RESULTS: Ninety patients were included during the study period, and 63 (70%) were men. The most common comorbidity was diabetes mellitus (n = 24, 27%), followed by solid cancers (n = 22, 24%). Antifungal therapy was administered to 50 (56%) patients, mostly voriconazole (n = 44). The in-hospital mortality rate was 49% (n = 44). Univariate analysis revealed that the risk factors for mortality included daily steroid dose, APACHE II score, SOFA score, C-reactive protein (CRP) level, carbapenem use, antifungal therapy, and caspofungin use. Multiple regression analysis identified four independent risk factors for mortality: age (Odds ratio [OR], 1.052, p = 0.013), daily steroid dose (OR, 1.057, p = 0.002), APACHE II score (OR, 1.094, p = 0.012), and CRP level (OR, 1.007, p = 0.008). Furthermore, the multivariable analysis identified that more physicians would initiate antifungal therapy for patients with prolonged steroid use (p = 0.001), lower white blood cell count (p = 0.021), and higher SOFA score (p = 0.048). Thus, under the selection bias, the independent risk factors for mortality in the antifungal treatment subgroup were daily steroid dose (OR, 1.046, p = 0.001) and CRP (OR, 1.006, p = 0.018), whereas the independent risk factor for mortality in the untreated group became APACHE II score (OR, 1.232, p = 0.007). CONCLUSIONS: Patients with IPA had a substantially high mortality. Overall, age, steroid use, APACHE II score, and CRP level were identified as the independent risk factors for mortality in patients in the ICU.

The Impacts of Aspergillosis on Outcome, Burden and Risks for Mortality in Influenza Patients with Critical Illness.

Previous studies have revealed higher mortality rates in patients with severe influenza who are coinfected with invasive pulmonary aspergillosis (IPA) than in those without IPA coinfection; nonetheless, the clinical impact of IPA on economic burden and risk factors for mortality in critically ill influenza patients remains undefined. The study was retrospectively conducted in three institutes. From 2016 through 2018, all adult patients with severe influenza admitted to an intensive care unit (ICU) were identified. All patients were classified as group 1, patients with concomitant severe influenza and IPA; group 2, severe influenza patients without IPA; and group 3, severe influenza patients without testing for IPA. Overall, there were 201 patients enrolled, including group 1 (n = 40), group 2 (n = 50), and group 3 (n = 111). Group 1 patients had a significantly higher mortality rate (20/40, 50%) than that of group 2 (6/50, 12%) and group 3 (18/11, 16.2%), p < 0.001. The risk factors for IPA occurrence were solid cancer and prolonged corticosteroid use in ICU of >5 days. Group 1 patients had significantly longer hospital stay and higher medical expenditure than the other two groups. The risk factors for mortality in group 1 patients included patients' Charlson comorbidity index, presenting APACHE II score, and complication of severe acute respiratory distress syndrome. Overall, IPA has a significant adverse impact on the outcome and economic burden of severe influenza patients, who should be promptly managed based on risk host factors for IPA occurrence and mortality risk factors for coinfection with both diseases.

Aggressive natural killer-cell neoplasm presenting in the marrow: a report of two cases including one with gains of chromosomes 4q and 9p.

Aggressive nature killer (NK)-cell neoplasm includes aggressive NK-cell leukemia (ANKL) and extranodal NK/T-cell lymphoma (ENKTL), nasal type. ANKL is rare and is characterized by a systemic neoplastic proliferation of NK-cells, usually with a leukemic presentation. ENKTL is a predominantly extranodal lymphoma, occurring mainly in the upper aerodigestive tract. Both are aggressive neoplasms strongly associated with Epstein-Barr virus (EBV). Here we report two patients with aggressive NK-cells neoplasms localized in the bone marrow (BM) who presented as prolonged fever, anemia, and thrombocytopenia. Both were treated initially as infectious disease. Imaging studies revealed splenomegaly without any nodular lesion or lymphadenopathy. BM examination revealed extensive involvement by EBV-positive NK-cells in both cases. Staging workup including nasal examination/biopsy was negative. Both patients passed away in a month. One case showed gains of chromosomes 4q and 9p by array comparative genomic hybridization. Both tumors were diagnostically challenging due to the unusual clinical presentation and absence of leukemic change, tumor mass or lymphadenopathy. Our cases demonstrate that lymphoma should be considered in patients with fever of unknown origin and bone marrow aspiration/biopsy should be performed as early diagnosis and novel therapeutic regimens may benefit these patients.

Cytomegalovirus colitis in intensive care unit patients: difficulties in clinical diagnosis.

PURPOSE: Cytomegalovirus (CMV) infection occurs increasingly in critically ill patients in intensive care units (ICUs). We reported CMV colitis which has rarely been recognized in the ICU patients. METHODS: CMV DNA was detected by polymerase chain reaction (PCR) for blood and/or stool samples. Definite diagnosis of CMV colitis required histopathology or CMV immunohistochemical staining of colorectal biopsies. We reviewed ICU patients characterized by positive blood or stool CMV-PCR with colorectal bleeding or water diarrhea. RESULTS: We identified 18 patients (biopsy-proved, n=8; probable cases, n=10). The most common comorbidities were chronic renal disease, diabetes mellitus, and coronary artery disease. Stool CMV-PCR was positive in 7 of 10 patients (2 of 3 biopsy-proved and 5 of 7 probable cases). Colonoscopy was performed for 15 patients, revealing ulcerative or polypoid lesions. The endoscopists obtained colonic biopsies from 9 patients. Yet, the pathologists reported CMV colitis for 4 patients. Additional 4 patients were confirmed using immunohistochemical stain by the request of clinical physicians. Pseudomembranous colitis was found in 4 patients. CONCLUSION: Diagnosis of CMV colitis seems difficult in clinical practice and need persistent communication between clinicians. The positive stool CMV-PCR result was a useful hint for adding immunohistochemical stain in mucosal biopsies to make a definite diagnosis of CMV colitis.

Rapidly fatal leukemia comprising pleomorphic large granular lymphocytes: a report of 2 cases.

BACKGROUND: Large granular lymphocytes (LGLs) are either cytotoxic T or natural killer (NK) cells exhibiting round nuclei and azurophilic cytoplasmic granules. Morphologically, neoplastic LGLs of T cell lineage (T-LGLLs) are usually indistinguishable from normal LGLs, while there is a wide morphological range of aggressive NK cell leukemia (ANKL). CASES: We present 2 consecutive cases of leukemia comprising pleomorphic LGLs. One patient presented with drowsy consciousness and unstable hemodynamics. Her peripheral blood smear disclosed a significant number of LGLs with pleomorphic nuclei expressing CD2, CD56 and HLA-DR but not surface or cytoplasmic CD3 (cCD3). The second patient, previously healthy, presented with a sudden death. Her peripheral blood revealed LGLs ranging from round to pleomorphic nuclei with a CD2+ cCD3+ surface CD3- CD56+ phenotype and clonally rearranged T cell receptor gene. The findings of the first patient were consistent with ANKL and the second, T-LGLL. Both patients passed away shortly before treatment. CONCLUSION: The 2 cases highlight the importance of a multidisciplinary approach in addition to cytological examination to reach accurate diagnoses of such rare leukemia cases.

Multicentric primary intestinal EBV-positive diffuse large B cell lymphoma of the elderly presenting with perforation.

Epstein-Barr virus (EBV)-positive diffuse large B cell lymphoma (DLBCL) of the elderly is a recently defined subgroup of DLBCL in the 2008 WHO classification of lymphoid neoplasms. It is characterized by an EBV-positive clonal B cell lymphoproliferation that occurs in patients aged over 50 years without any known immunodeficiency. This disease shows frequent extranodal involvement, a morphological spectrum from polymorphous to monomorphic large cells, and a poor prognosis. We reported the case of a 75-year-old male who had a primary intestinal multicentric EBV(+) DLBCL and presented with perforation, the first multicentric case in the literature. The monomorphic tumor cells exhibited extensive necrosis and expressed CD20, CD138, and EBNA2 with diffuse positivity for EBV by in situ hybridization. Quantitative real-time PCR revealed a low serum EBV viral load. The patient passed away in 10 days. His poor outcome was probably due to perforation, age over 70, the presence of B symptoms, poor general condition, and high performance score.

Cardiotoxin III induces c-jun N-terminal kinase-dependent apoptosis in HL-60 human leukaemia cells.

Cardiotoxin III (CTX III), a basic polypeptide with 60 amino acid residues isolated from Naja naja atra venom, has been reported to have anticancer activity. The molecular effects of CTX III on HL-60 cells were dissected in the present study. We found that the antiproliferative action of CTX III on HL-60 cells was mediated through apoptosis, as characterized by an increase of sub G1 population, DNA fragmentation and poly(ADP-ribose) polymerase (PARP) cleavage. Upregulation of Bax, downregulation of Bcl-2, the release of mitochondrial cytochrome c to cytosol and the activations of capase-9 and -3 were noted, while CTX III had no appreciable effect on the levels of Bcl-X(L) and Bad proteins. Moreover, c-Jun N-terminal kinase (JNK) was activated shortly after CTX III treatment in HL-60 cells. Consistently, the SP600125 compound, an anthrapyrazolone inhibitor of JNK, suppressed apoptosis induced by CTX III. As expected, this JNK inhibitor also attenuated the modulation of Bax and Bcl-2, as well as the cytosolic appearance of cytochrome c and the activation of caspase-3 and caspase-9 that induced by CTX III. These findings suggest that CTX III can induce apoptosis in HL-60 cells via the mitochondrial caspase cascade and the activation of JNK is critical for the initiation of the apoptotic death of HL-60 cells.