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.

Clinical presentations and prognosis of metformin-associated lactic acidosis patients in the intensive care unit: A 20-year survey.

METHODS: We retrospectively analyzed 82 adult patients with MALA admitted to the ICU over 20 years. The association between the clinical parameters and mortality post-MALA was estimated using logistic regression analysis. RESULTS: Patients with MALA admitted to the ICU presented with clinical symptoms mainly associated with the head (40.24%), chest (41.46%), and abdomen (35.37%). Additionally, the PLL distribution significantly varied with age, APACHE II = Acute Physiology and Chronic Health Evaluation II (APACHE II) score, various laboratory parameters like nadir arterial bicarbonate level, multiple treatment modalities such as renal replacement therapy, and mortality. The overall mortality rate was 17.07%. After adjustment of age and gender, the significant predictors of mortality were APACHE II score, PLL, vasoactive support, ventilator support, and cardiopulmonary resuscitation. CONCLUSIONS: Despite MALA being a rare event, it is necessary to evaluate its clinical characteristics, especially the associated PLL and mortality. In the current study, higher levels of APACHE II score and PLL show a greater likelihood of mortality in MALA patients.

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.

Comparing machine learning with case-control models to identify confirmed dengue cases.

In recent decades, the global incidence of dengue has increased. Affected countries have responded with more effective surveillance strategies to detect outbreaks early, monitor the trends, and implement prevention and control measures. We have applied newly developed machine learning approaches to identify laboratory-confirmed dengue cases from 4,894 emergency department patients with dengue-like illness (DLI) who received laboratory tests. Among them, 60.11% (2942 cases) were confirmed to have dengue. Using just four input variables [age, body temperature, white blood cells counts (WBCs) and platelets], not only the state-of-the-art deep neural network (DNN) prediction models but also the conventional decision tree (DT) and logistic regression (LR) models delivered performances with receiver operating characteristic (ROC) curves areas under curves (AUCs) of the ranging from 83.75% to 85.87% [for DT, DNN and LR: 84.60% ± 0.03%, 85.87% ± 0.54%, 83.75% ± 0.17%, respectively]. Subgroup analyses found all the models were very sensitive particularly in the pre-epidemic period. Pre-peak sensitivities (<35 weeks) were 92.6%, 92.9%, and 93.1% in DT, DNN, and LR respectively. Adjusted odds ratios examined with LR for low WBCs [≤ 3.2 (x103/µL)], fever (≥38°C), low platelet counts [< 100 (x103/µL)], and elderly (≥ 65 years) were 5.17 [95% confidence interval (CI): 3.96-6.76], 3.17 [95%CI: 2.74-3.66], 3.10 [95%CI: 2.44-3.94], and 1.77 [95%CI: 1.50-2.10], respectively. Our prediction models can readily be used in resource-poor countries where viral/serologic tests are inconvenient and can also be applied for real-time syndromic surveillance to monitor trends of dengue cases and even be integrated with mosquito/environment surveillance for early warning and immediate prevention/control measures. In other words, a local community hospital/clinic with an instrument of complete blood counts (including platelets) can provide a sentinel screening during outbreaks. In conclusion, the machine learning approach can facilitate medical and public health efforts to minimize the health threat of dengue epidemics. However, laboratory confirmation remains the primary goal of surveillance and outbreak investigation.

High-level ambient particulate matter before influenza attack with increased incidence of Aspergillus antigenemia in Southern Taiwan, 2016.

We found significant correlation between the incidence of severe influenza and Aspergillus antigenemia among medical intensive care unit patients for 7-month observation (coefficient γ=0.976, p<0.001). High-level ambient pollution was noticed for 2 months before the epidemic, highlighting that influenza patients might coinfect with aspergillosis in the community.

Role of the Diphosphine Chelate in Emissive, Charge-Neutral Iridium(III) Complexes.

A class of neutral tris-bidentate IrIII metal complexes incorporating a diphosphine as a chelate is prepared and characterized here for the first time. Treatment of [Ir(dppBz)(tht)Cl3 ] (1, dppBz=1,2-bis(diphenylphosphino)benzene, tht=tetrahydrothiophene) with fppzH (3-trifluoromethyl-5-(2'-pyridyl)-1H-pyrazole) afforded the dichloride complexes, trans-(Cl,Cl)[Ir(dppBz)(fppz)Cl2 ] (2) and cis-(Cl,Cl)[Ir(dppBz)(fppz)Cl2 ] (3). The reaction of 3 with the dianionic chelate precursor, 5,5'-di(trifluoromethyl)-3,3'-bipyrazole (bipzH2 ) or 5,5'-(1-methylethylidene)-bis(3-trifluoromethyl-1H-pyrazole) (mepzH2 ), in DMF gave the tris-bidentate complex [Ir(dppBz)(fppz)(bipz)] (4) or [Ir(dppBz)(fppz)(mepz)] (5), respectively. In contrast, a hydride complex [Ir(dppBz)(fppz)(bipzH)H] (6) was isolated instead of 4 in protic solvent, namely: diethylene glycol monomethyl ether (DGME). All complexes 2-6 are luminescent in powder form and thin films where the dichlorides (2, 3) emit with maxima at 590-627 nm (orange) and quantum yields (QYs) up to 90 % whereas the tris-bidentate (4, 5) and hydride (6) complexes emit at 455-458 nm (blue) with QYs up to 70 %. Hybrid (time-dependent) DFT calculations showed considerable metal-to-ligand charge transfer contribution to the orange-emitting 2 and 3 but substantial ligand-centered 3 π-π* transition character in the blue-emitting 4-6. The dppBz does not participate in the radiative transitions in 4-6, but it provides the rigidity and steric bulk needed to promote the luminescence by suppressing the self-quenching in the solid state. Fabrication of an organic light-emitting diode (OLED) with dopant 5 gave a deep-blue CIE chromaticity of (0.16, 0.15). Superior blue emitters, which are vital in OLED applications, may be found in other neutral IrIII complexes containing phosphine chelates.

First N-Borylated Emitters Displaying Highly Efficient Thermally Activated Delayed Fluorescence and High-Performance OLEDs.

Despite the fast boom of thermally activated delayed fluorescence (TADF) emitters bearing borane-based acceptor, so far, no TADF emitter with a direct B-N linkage between N-donor and boryl acceptor has been reported. The latter should simplify the molecular architecture and hence facilitate the synthetic design and versatility. We report here the preparation and characterization of a new series of N-borylated compounds with functional acridine donor unit; namely: ACBM, PACBM, and SACBM. Spectroscopic studies were performed to explore their photophysical properties that exhibited prominent solvatochromism and thermally activated delayed fluorescence. The time-dependent DFT calculation indicated the involvement of substantial intramolecular charge transfer character for which HOMO and LUMO are spatially separated. For compound SACBM, fabrication of green emitting OLED gave CIE chromaticity of (0.22, 0.59) and maximum external quantum efficiency, luminance efficiency and power efficiency of 19.1%, 60.9 cd/A, and 43.6 lm/W, respectively, demonstrating for the first time the highly efficient OLEDs using N-borylated TADF emitters.

Higher mortality of severe influenza patients with probable aspergillosis than those with and without other coinfections.

BACKGROUND/PURPOSE: Aspergillus-associated infection might comprise up to 23-29% of severe influenza patients from the community throughout stay in an intensive care unit (ICU). In Taiwan, cases of severe influenza with aspergillosis are increasingly reported. Therefore, we describe the relative risk of mortality among severe influenza patients with aspergillosis and other coinfections compared to severe influenza patients without Aspergillus coinfections. METHODS: We retrospectively reviewed 124 adult patients with severe influenza in a tertiary medical center in southern Taiwan from January 2015 through March 2016. The definition of probable aspergillosis required abnormal radiological findings and positive Aspergillus galactomannan (GM) antigen and/or Aspergillus isolation. RESULTS: Probable aspergillosis (detected throughout the whole course) and other coinfections (only community-acquired) were diagnosed in 21 (17%) and 38 (31%) of all patients respectively. Klebsiella pneumoniae (36.8%), Pseudomonas aeruginosa (31.6%) and Staphylococcus aureus (31.6%) were the most frequent isolates of other coinfections. In-ICU mortality of Aspergillus group (66.7%) was significantly higher than other coinfections (23.7%, p = 0.001) or control group without coinfections (15.4%, p < 0.001), with significant odds ratios after adjusting for important variables. The factor of GM index ≥0.6 had a 19.82 (95% CI, 4.91 to 80.07, p < 0.0001) odds of expiring in an ICU among the Aspergillus group. CONCLUSION: Dual Aspergillus and influenza infection is emerging in southern Taiwan. Meanwhile, community-acquired P. aeruginosa should be listed in the common copathogens with severe influenza. The 67% mortality linked to aspergillosis highlights the need for physicians to focus attention on patients with GM ≥ 0.6.

Prognosis of alcohol-associated lactic acidosis in critically ill patients: an 8-year study.

Lactic acidosis is common in critical care; by contrast, a subtype called alcohol-associated lactic acidosis (AALA) is rarely encountered. The primary purpose of this study was to determine the prognosis of AALA in critically ill patients and the second aim was to determine whether the survival was associated to the peak blood lactate concentration. An 8-year retrospective analysis of adult patients admitted to the intensive care unit (ICU) with AALA between January 2007 and December 2014 was considered in a tertiary care hospital. In total, 23 patients were analyzed and the median peak blood lactate level was 15.9 mmol/L. Only 2 patients (8.7%) presented peak blood lactate levels <10 mmol/L. In this study, 21 patients survived from ICU and hospital, the mortality rate was 8.7%. The result indicted the survival of AALA was not associated with peak blood lactate concentration although survivors still had a better lactate clearance rate per hour than non-survivors. Moreover, AALA patients with coexisting sepsis presenting higher lactate clearance rate and shorter lactate clearance time than those of AALA patients with solely sepsis-related lactic acidosis.

Risk of Diabetes Mellitus after First-Attack Acute Pancreatitis: A National Population-Based Study.

OBJECTIVES: Population-based data on the risk of diabetes mellitus onset after acute pancreatitis (AP) are lacking. We assessed the incidence of diabetes in AP survivors compared with matched controls. METHODS: The study cohort, drawn from Taiwan National Health Insurance claims data, included 2,966 first-attack AP patients and 11,864 non-AP general controls individually matched on age and sex, with an AP/non-AP ratio of 1:4. Incidence rate was estimated under Poisson assumption. Relative risks of diabetes were indicated by hazard ratios (HRs) estimated from Cox proportional hazard regression models with a partitioning of time at 3 months to account for proportionality. RESULTS: In the first partition of time (<3 months), the incidences of diabetes were 60.8 and 8.0 per 1,000 person-years in AP and control groups, respectively; representing a covariate-adjusted HR of 5.90 (95% confidence interval (CI) 3.37-10.34). In the second partition (≥3 months), the incidences of diabetes were 22.5 and 6.7 per 1,000 person-years in AP and control groups, respectively (adjusted HR 2.54, 95% CI 2.13-3.04). In the second partition, the risk of diabetes was greater in men than in women (HR 3.21 vs. 1.58, P=0.0004). When the analyses were stratified by severity of AP, the results for mild AP were similar to those for all AP. CONCLUSIONS: The risk of diabetes increases by twofold after AP; therefore, a long-term screening is necessary to evaluate diabetes after an attack regardless of severity. Further research should be conducted to develop cost-effective follow-up strategies, and to elucidate the underlying mechanisms of the relationship between diabetes and AP.

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.

Acute symptomatic hydrocephalus in Listeria monocytogenes meningitis.

Listeria monocytogenes meningitis appears to have increased in incidence. Although most reported cases of listeriosis involve the central nervous system, brain computed tomography is usually normal. Hydrocephalus is a common complication of tuberculous meningitis, which has a high prevalence in Taiwan. However, patients with L. monocytogenes meningitis rarely develop the complication of symptomatic hydrocephalus. We report a patient with L. monocytogenes meningitis who presented with persistent alteration of consciousness after appropriate antimicrobial therapy. Follow-up brain computed tomography revealed acute hydrocephalus. An Ommaya reservoir was implanted, and daily drainage of the cerebrospinal fluid was performed. The patient improved gradually and his mental status recovered completely 4 days later. This case should remind physicians to be aware of the possible occurrence of hydrocephalus in L. monocytogenes meningitis and that prompt cerebrospinal fluid drainage may achieve a good outcome.