Pediatric tympanostomy tube assessment via deep learning.

PURPOSE: Tympanostomy tube (TT) placement is the most frequently performed ambulatory surgery in children under 15. After the procedure it is recommended that patients follow up regularly for "tube checks" until TT extrusion. Such visits incur direct and indirect costs to families in the form of days off from work, copays, and travel expenses. This pilot study aims to compare the efficacy of tympanic membrane (TM) evaluation by an artificial intelligence algorithm with that of clinical staff for determining presence or absence of a tympanostomy tube within the TM. METHODS: Using a digital otoscope, we performed a prospective study in children (ages 10 months-10 years) with a history of TTs who were being seen for follow up in a pediatric otolaryngology clinic. A smartphone otoscope was used by study personnel who were not physicians to take ear exam images, then through conventional otoscopic exam, ears were assessed by a clinician for tubes being in place or tubes having extruded from the TM. We trained and tested a deep learning (artificial intelligence) algorithm to assess the images and compared that with the clinician's assessment. RESULTS: A total of 123 images were obtained from 28 subjects. The algorithm classified images as TM with or without tube in place. Overall classification accuracy was 97.7 %. Recall and precision were 100 % and 96 %, respectively, for TM without a tube present, and 95 % and 100 %, respectively, for TM with a tube in place. DISCUSSION: This is a promising deep learning algorithm for classifying ear tube presence in the TM utilizing images obtained in awake children using an over-the-counter otoscope available to the lay population. We are continuing enrollment, with the goal of building an algorithm to assess tube patency and extrusion.

Fluctuation of BCR-ABL1 qPCRIS level beyond 0.1%IS after stopping tyrosine kinase inhibitor in chronic myeloid leukaemia patients with deep molecular response for at least two years.

Fluctuation of BCR-ABL1 real-time quantitative polymerase chain reaction in International Scale (qPCRIS) level below major molecular response (MMR) (0.1%IS) is a known phenomenon after stopping tyrosine kinase inhibitor (TKI) in chronic myeloid leukaemia (CML) patients who are attempting treatment free remission (TFR). We report here four cases of fluctuation beyond MMR during conduct of a Malaysia Stop TKI Trial (MSIT) to examine the validity of the commonly used relapse criterion - loss of MMR for one reading - aiming to provide evidence in setting relapse criteria for future CML patients who want to attempt TFR.

Reference interval establishment of full blood count extended research parameters in the multi-ethnic population of Malaysia.

Haematological cellular structures may be elucidated using automated full blood count (FBC) analysers such as Unicel DxH 800 via cell population data (CPD) analysis. The CPD values are generated by calculating volume, conductivity, and five types of scatter angles of individual cells which would form clusters or populations. This study considered 126 CPD parameter values of 1077 healthy Malaysian adults to develop reference intervals for each CPD parameter. The utility of the CPD reference interval established may range from understanding the normal haematological cellular structures to analysis of distinct cellular features related to the development of haematological disorders and malignancies.

Selection of reference genes for quantitative studies in acute myeloid leukaemia.

INTRODUCTION: Quantitative polymerase chain reaction (qPCR) is commonly used in the investigation of acute myeloid leukaemias (AML). Stable reference genes (RG) are essential for accurate and reliable reporting but no standard method for selection has been endorsed. MATERIALS AND METHODS: We evaluated simple statistics and published model-based approaches. Multiplex-qPCR was conducted to determine the expression of 24 candidate RG in AMLs (N=9). Singleplex-qPCR was carried out on selected RG (SRP14, B2M and ATP5B) and genes of interest in AML (N=15) and healthy controls, HC (N=12). RESULTS: RG expression levels in AML samples were highly variable and coefficient of variance (CV) ranged from 0.37% to 10.17%. Analysis using GeNorm and Normfinder listed different orders of most stable genes but the top seven (ACTB, UBE2D2, B2M, NF45, RPL37A, GK, QARS) were the same. In singleplex-qPCR, SRP14 maintained the lowest CV in AML samples. B2M, one of most stable reference genes in AML, was expressed near significantly different in AML and HC. GeNorm selected ATP5B+SRP14 while Normfinder chose SRP14+B2M as the best two RG in combination. The median expressions of combined RG genes in AML compared to HC were less significantly different than individually implying smaller expression variation after combination. Genes of interest normalised with RG in combination or individually, displayed significantly different expression patterns. CONCLUSIONS: The selection of best reference gene in qPCR must consider all sample sets. Model-based approaches are important in large candidate gene analysis. This study showed combination of RG SRP14+B2M was the most suitable normalisation factor for qPCR analysis of AML and healthy individuals.

Incidence and risk factors for incomplete HBV DNA suppression in HIV/HBV-co-infected patients initiating tenofovir-based therapy.

Suppression of hepatitis B virus (HBV)-DNA to undetectable levels is an important goal for HIV/HBV-co-infected patients receiving anti-HBV-active antiretroviral therapy (ART), and current guidelines recommend that this outcome should be reached by 1 year of treatment. However, the proportion of patients that fail to achieve an undetectable HBV DNA at this time point and its determinants remain unknown in clinical practice. The objective of this study was to determine the incidence and risk factors for incomplete HBV suppression following 1 year of tenofovir-based ART. We performed a cohort study among tenofovir-treated HIV/HBV-co-infected patients. Patients had HBV viraemia, initiated tenofovir-based ART and had HBV DNA measured at 1 year of therapy. The primary outcome was incomplete HBV suppression (HBV DNA ≥2.6 log IU/mL) at 1 year. Logistic regression determined odds ratio (ORs) of incomplete HBV suppression for risk factors of interest. Among 133 patients, 54% (95% CI, 46-63%) had incomplete HBV suppression at 1 year. Incomplete suppression was associated with higher baseline HBV DNA (OR, 1.46 per log IU/mL increase; 95% CI, 1.1-1.94) and detectable HIV viraemia at 1 year (OR, 2.52; 95% CI, 1.19-5.32). Among 66 patients with suppressed HIV RNA at 1 year, 28 (42%) failed to achieve an undetectable HBV DNA. Failure to suppress HBV DNA by 1 year occurred in a sizeable proportion of tenofovir-treated HIV/HBV-co-infected patients. Higher HBV DNA and detectable HIV viraemia were risk factors for incomplete HBV suppression.

MicroRNA (miRNA) expression profiling of peripheral blood samples in multiple myeloma patients using microarray.

MicroRNAs (miRNAs) are mostly located at cancer-associated genomic regions or in fragile sites, suggesting their important role in the pathogenesis of human cancers. Multiple myeloma (MM) is a cancer of plasma cells, the third most common cancer of the blood after lymphoma and leukaemia. There are several published reports on miRNAs in MM, however most used bone marrow rather than peripheral blood samples. The aim of this study is to characterise miRNA expression in normal and MM patients using peripheral blood samples as it is less invasive and is readily available from patients. Blood samples from 35 MM patients were analysed using the microarray method. We identified up-regulation of 36 miRNAs (57%) and down-regulation of 27 miRNAs (43%). We also identified the CCND2, HMGA2 and IGF1R genes were among the highly predictive target genes (P(CT) > 0.80) for most of the deregulated miRNAs. These genes are known to play important roles in MM as well as other cancers. Five miRNAs (let-7c, miR-16, miR- 449, miR-181a and miR-181b) were found to exhibit similar expression patterns (p < 0.05) in peripheral blood when compared to data obtained by using bone marrow aspirates from MM patients in other studies. In conclusion, our study has demonstrated that miRNAs are also present and differentially expressed in the peripheral blood of MM patients compared to controls and may potentially serve as candidate tumour biomarkers in MM. In particular, let-7c and miR-16 have been shown to be significantly expressed in the bone marrow.

Thalassaemia screening among students in a secondary school in Ampang, Malaysia.

Thalassaemia is a common disorder in Malaysia. It is estimated that 4.5% of the population are carriers for beta- or alpha- thalassaemias. We set out to screen Form 4 students aged between 15 and 16 years old in a national school, for thalassaemia in March 2008. Written consent was obtained from 310 students. The carrier rate for the common thalassaemia syndromes was 6.8% (2.9% for beta-thalassaemia, 2.6% for HbE and 1.3% for two-gene deletion for alpha-thalassaemia). Carriers for beta-thalassaemia and two-gene deletion for alpha-thalassaemia were more common in the Chinese (4.3% and 1.4% respectively) while heterozygous HbE was more common in the Malays (3.8%). The laboratory cost of screening one student was RM 45 and the total number of man-hours spent in this screening activity was 600. This screening exercise showed that thalassaemia carriers are common among the Chinese and Malays and it is feasible to carry out a screening programme for secondary school students.

Determinants of viral clearance and persistence during acute hepatitis C virus infection.

The virological and immunological features of hepatitis C virus (HCV) infection were studied weekly for 6 months after accidental needlestick exposure in five health care workers, four of whom developed acute hepatitis that progressed to chronicity while one subject cleared the virus. In all subjects, viremia was first detectable within 1-2 weeks of inoculation, 1 month or more before the appearance of virus-specific T cells. The subject who cleared the virus experienced a prolonged episode of acute hepatitis that coincided with a CD38+ IFN-gamma- CD8+ T cell response to HCV and a small reduction in viremia. Subsequently, a strong CD4+ T cell response emerged and the CD8+ T cells became CD38- and started producing IFN-gamma in response to HCV, coinciding with a rapid 100,000-fold decrease in viremia that occurred without a corresponding surge of disease activity. Chronic infection developed in two subjects who failed to produce a significant T cell response and in two other subjects who initially mounted strong CD4+ T cell responses that ultimately waned. In all subjects, viremia was higher at the peak of acute hepatitis than it was when the disease began, and the disease improved during the viremia. These results provide the first insight into the host-virus relationship in humans during the incubation phase of acute HCV infection, and they provide the only insight to date into the virological and immunological characteristics of clinically asymptomatic acute HCV infection, the commonest manifestation of this disease. In addition, the results suggest that the vigor and quality of the antiviral T cell response determines the outcome of acute HCV infection, that the ability of HCV to outpace the T cell response may contribute to its tendency to persist; that the onset of hepatitis coincides with the onset of the CD8+ T cell response, that disease pathogenesis and viral clearance are mediated by different CD8+ T cell populations that control HCV by both cytolytic and noncytolytic mechanisms, and that there are different pathways to viral persistence in asymptomatic and symptomatic acute HCV infection.

National Cancer Patient Registry--Haematology Malignancy (NCPR-HM).

Treatment option of Haematological malignancies has expanded over the last decade. The outcome of treatment is expected to be better compare to previously. However, study of treatment outcome for haematological malignancies has not been carried out in Malaysia. The goal of this study is to measure the treatment outcome in patients with haematological malignancy.

Quantitative analysis of the peripheral blood cytotoxic T lymphocyte response in patients with chronic hepatitis C virus infection.

Hepatitis C virus (HCV)-specific cytotoxic T lymphocytes (CTL) are present in the peripheral blood and liver of chronically infected patients. The current study was performed to study the relationship between the strength of the CTL response, liver disease severity, and viral load. The results may be summarized as follows: first, using CTL precursor frequency (CTLpf) analysis to quantitate the peripheral blood CTL response, chronically infected patients were less strongly sensitized to a panel of well-defined HCV epitopes than they were to an epitope within the influenza matrix protein. Second, HCV-specific CTLpf did not correlate with disease activity or viral load in the majority of patients on a cross-sectional basis, although it did increase in three patients concomitant with sharp increases in liver disease. Finally, interferon therapy did not enhance the CTLpf against the HCV epitopes studied in these patients, indicating that its antiviral effect is independent of the CTL response. Since the HCV-specific CTLpf in the blood is actually quite low, the CTL may contribute to ongoing liver disease in these patients while being quantitatively inadequate to destroy all of the infected hepatocytes, thereby facilitating HCV persistence and contributing to chronic liver disease.

Immunological significance of cytotoxic T lymphocyte epitope variants in patients chronically infected by the hepatitis C virus.

This study was performed to test the hypothesis that cytotoxic T lymphocyte (CTL) selection of hepatitis C virus (HCV) escape variants plays a role in HCV persistence. The peripheral blood CTL responsiveness of patients with well-established chronic hepatitis C to a panel of 10 prototype HCV peptides (genotype 1a) was compared with the corresponding sequences encoded by the infecting viruses in each patient. Variant viral peptide sequences were threefold more frequent in the presence of a CTL response than in its absence, and CTL responses were detected nearly twice as often in association with variant rather than with prototype viral peptide sequences. Furthermore, over half of the patients were infected with potential CTL escape variants that contained nonimmunogenic and noncross-reactive variant peptides many of which displayed reduced HLA-binding affinity. Surprisingly, follow up analysis over a period of up to 46 mo revealed that, in contrast to the relatively high frequency of escape variants initially observed, the subsequent emergence rate of CTL escape variants was very low. Interestingly, the one escape variant that was detected proved to be a CTL antagonist. Collectively, these observations suggest that CTL selection of epitope variants may have occurred in these patients before their entrance into the study and that it may have played a role in HCV persistence. The low apparent rate of ongoing CTL selection in chronically infected patients, however, suggests that if CTL escape occurs during HCV infection it is probably an early event.

Recognition of a novel naturally processed, A2 restricted, HCV-NS4 epitope triggers IFN-gamma release in absence of detectable cytopathicity.

Using short term CTL lines derived from HLA A2/Kb transgenic mice and IFN-gamma release assays we demonstrate that the NS4.1769 epitope, is generated from natural processing of the NS4 antigen, and presented in the context of the A2/Kb molecules. Interestingly, T cell recognition of the naturally processed form of the NS4. 1769 epitope was associated with significant IFN-gamma release, but no direct cytolytic activity. Epitopes of this phenotype might be of interest, in terms of therapy of chronic HCV infection by associating the benefit of localized lymphokine release with low or absent direct cytopathicity.

Large cell neuroendocrine carcinoma of the ampulla of Vater with glandular differentiation.

Large cell neuroendocrine carcinoma of the ampulla of Vater is extremely rare. A 55 year old woman presented with an ampullary tumour causing pancreaticobiliary obstruction and a pancreaticoduodenectomy was performed. Microscopically, the tumour was diagnosed as a CD117 positive large cell neuroendocrine carcinoma with glandular differentiation. Four months later the patient developed a general recurrence. The metastatic tumours showed CD117 negativity and pure neuroendocrine features. The patient died of disease six months after diagnosis. It is postulated that the two components originated from a common multipotential stem cell. The clinical behaviour of ampullary large cell neuroendocrine carcinomas appears to be highly aggressive, with early metastases and a fatal outcome.

Immunoreactivity of nm23-H1 protein in renal cell carcinoma.

Formalin-fixed, paraffin-embedded tissue blocks from 25 surgical specimens of renal cell carcinoma (RCC) including 13 adjacent normal renal tissues were investigated. The specimens were examined by immunohistochemistry using the monoclonal antibody, nm23-H1. The positive immunostaining of nm23-H1 protein was confined primarily to the cytoplasm of both normal renal tubular epithelial cells and renal tumor cells. Immunostaining of nm23-H1 protein was reduced significantly in RCC as compared to the normal renal tissues (P = 0.003). The positive immunostaining of nm23-H1 protein was seen in 92% (12/13) of normal renal tissues and in 60% (15/25) of RCC. No relationship was found between immunostaining of nm23-H1 protein and the patient's clinicopathological factors including age, tumor size, tumor location, tumor grade and tumor stage. Furthermore, immunostaining of nm23-H1 protein was not correlated with patient survival. Although immunoreactivity of nm23-H1 protein in patients with RCC was not correlated with survival, nm23-H1 protein may play a role in human renal tubular tumorigenesis.

Inhibitory activity of cigarette-smoke condensate on the mutagenicity of heterocyclic amines.

Cigarette-smoke condensate (CSC) is a complex mixture containing over 3800 identified chemicals including nicotine, water, mutagens, antimutagens, cytotoxins and inert chemicals. Although CSC is mutagenic in the Ames test, its effect on the activity of other mutagens has not been characterized. Using the Ames Salmonella bacterial mutagenesis assay, we found CSC exerts a significant inhibitory effect on mutagens requiring bioactivation. Those studied included heterocyclic amines (Glu-P-1, Glu-P-2, IQ, MeIQ, Trp-P-1 and Trp-P-2), benzo[a]pyrene (B[a]P) and aflatoxin B1. However, CSC had no effect on the activity of direct-acting mutagens (2-nitrofluorene, sodium azide, 4-nitro-1,2-phenylenediamine, 4-nitroquinoline N-oxide and methyl methanesulfonate). With indirect-acting mutagens, the reduced number of revertants observed in the presence of CSC was not attributable to cytotoxicity. CSC exhibited a potent inhibitory effect on the cytochrome P-450 dependent monooxygenases, ethoxyresorufin O-deethylase and B[a]P hydroxylase. This suggests inhibition of the cytochrome P-450 isozymes as one possible mechanism for the antimutagenicity of CSC. Fractionation studies of CSC revealed that the neutral, weakly acidic (phenolic) and basic fractions are all effective as antimutagens against Glu-P-1, a representative heterocyclic amine. This indicates that several classes of chemicals contribute to the inhibitory effect of CSC on the mutagenicity of the heterocyclic amines.

Clinical evaluation of electronic and manual constant force probes.

The objective of this study was to compare the measurements of an electronic controlled-force probe (FP) to that of a manual controlled-force probe (SP) and a conventional probe (CP). Twelve subjects were recruited. A quadrant with no missing teeth (excluding third molars) was selected. Probing depth was measured at 6 sites per tooth (mesiobuccal, buccal, distobuccal, mesiolingual, lingual, and distolingual) by two examiners (AK and KC) each using the three probes in the following sequence: FP, SP, and CP. The same measurements were repeated a week later by both examiners. The mean difference of measurements between CP and FP was 0.375 +/- 0.858 mm (P < 0.05), with 52.7% of the measurements within 0.5 mm and 80% within 1.0 mm. Correlation between measurements was high (0.7208) and significant (P < 0.001). The mean difference between SP and FP was 0.450 +/- 0.863 mm (P < 0.05), with 49.1% of the measurements within 0.5 mm and 76.9% within 1.0 mm. Correlation between measurements was high (0.7354) and significant (P < 0.001). The mean difference between CP and SP was -0.074 +/- 0.373 mm (P < 0.05), with 49.1% of the measurements within 0.5 mm and 76.9% within 1.0 mm. Correlation between measurements was high (0.95) and significant (P < 0.001). Intra-examiner differences varied for each examiner. For both examiners, the correlations for FP (AK = 0.77, KC = 0.46) were lower than that for CP (AK = 0.86, KC = 0.80) and SP (AK = 0.86, KC = 0.83). Inter-examiner comparisons showed that the correlation for FP (0.50) was lower than that for CP (0.85) and SP (0.86). The percentage of sites within 1 mm differences was less for FP (70%) than for CP (94%) or SP (94%). In conclusion, both CP and SP correlated well with FP. None of the three probes investigated completely eliminated probing errors. The CP and SP yielded more reproducible measurements than FP. Regardless of the type of probe used, probing measurements are subject to both intra- and interexaminer errors.

Colonization and persistence of rough and smooth colony variants of Actinobacillus actinomycetemcomitans in the mouths of rats.

Fresh isolates of Actinobacillus actinomycetemcomitans (Aa) bind avidly to surfaces in vitro, but existing in vivo studies of the adherence of Aa are limited. This study had two goals: (1) to compare the oral colonization of two isogenic strains of Aa-CU1010, a clinical isolate that expresses the adherent phenotype, and CU1012, a minimally adherent laboratory variant-and (2) to check for phenotypic reversion of these strains in a clinical setting. Rifampicin-resistant strains, developed for tracking in Sprague-Dawley rats, were tested in vitro to determine their stability and binding. In study 1, after antibiotic suppression, six rats (group I) received CU1010 in their feed. The eight rats in group II received CU1012 in their feed and four were supplemented by oral swabbing and four by gastric gavage. Group III consisted of three sham-inoculated controls. All rats were inoculated for 4 days. Microbiological data were collected at 1, 4 and 8 weeks after inoculation. Supporting data were supplied by antibody titres and clinical measures of alveolar bone loss. Study 2 consisted of six rats in each of three groups as above, but tagged strains of Aa were delivered by food alone. At all time-points in both studies, Aa was absent before inoculation and controls had no Aa or antibody to Aa. In study 1, all six rats in group I yielded positive cultures for Aa at 8 weeks. In group II, five of eight had positive cultures for Aa at 1 week, two of eight at 4 weeks and none had Aa at 8 weeks (P < or =0.001). All six rats in group I had serum anti-Aa titres compared to group II, where titres were seen in four of eight rats (P < or =0.015). In vitro data paralleled those found in vivo. No phenotypic reversion of either strain was seen in vivo. In study 2, four of six rats in group I showed Aa and had titres to Aa, while no other animals showed Aa at any time. The model provides convincing evidence that, unlike laboratory variants, clinical isolates colonize, persist and integrate into an already established, albeit reduced, econiche.

Epidermal growth factor in gingival crevicular fluid and its binding capacity in inflamed and non-inflamed human gingiva.

Epidermal growth factor (EGF) is a pro-inflammatory small peptide (6000 Da) with a variety of biological activities including stimulation of cell differentiation and mediation of proteolysis by binding to its specific receptor on the cell surface. The purpose of this study was to determine the levels of EGF in gingival crevicular fluid (GCF) and the EGF-binding capacity to its receptor in gingival tissue. The GCF samples were collected from six patients by inserting paper strips into shallow (< 5 mm) and deep pockets (> or = 5 mm) for 30 s. The strips were soaked in 0.2 M acetate for extraction and the EGF in the supernatants was analysed by radioimmunoassay. To determine the binding capacity of EGF to its receptor, inflamed gingival tissues (pocket depth > or = 5 mm, Gingival Index = 1, 2 or 3) were collected during periodontal flap surgery and non-inflamed gingival tissues (pocket depth < 5 mm, Gingival Index = 0) were collected during surgical "crown lengthening' for aesthetic purposes. The tissues were pooled by group, homogenized for membrane preparation and the supernatants obtained after centrifugation were used in a 125IEGF binding assay. To determine the effect of inflammation on gingival EGF receptor, inflamed and non-inflamed gingival tissues were collected from six patients and prepared similarly to the binding assay. Gingival preparations were then electrophoresed for Western blot analysis with EGF receptor antiserum. The EGF level in GCF was significantly lower (P < 0.05) in the samples collected from pockets > or = 5 mm (0.9 +/- 0.6 ng/ml) than in those from pockets < 5 mm (2.4 +/- 2.1 ng/ml). The average Gingival Index was higher (2.6 +/- 0.6) in pockets > or = 5 mm than in pockets < 5 mm (1.4 +/- 1.0). Specific binding of 125I-EGF to its receptor in inflamed gingiva was 2.7-fold higher than in non-inflamed gingiva (14.4 +/- 4.9 vs 5.4 +/- 1.8 fmol/g wet tissue). Western blot analysis showed two major immunoreactive bands (180 and 120 kDa), which represent EGF receptor and its degradation products, in inflamed gingiva. The findings show that inflammation activates EGF binding capacity in gingiva and that the up-regulation of EGF receptor in inflamed gingiva might be associated with a lowered concentration of EGF in GCF produced adjacent to inflamed gingiva. This up-regulation of EGF receptor during inflammation might be an important mechanism in the pathogenesis of periodontal disease.

Diagnosis of an advanced endodontic/periodontic lesion: report of a case.

Diagnosis of endodontic/periodontic lesions is often a challenge for clinicians. Treatment will not be successful without correct diagnosis. This article presents an advanced case of an endodontic/periodontic lesion in a patient who was referred to a periodontist. After careful examination of the patient, as well as consultation with an endodontist, an endodontic diagnosis was made and the patient treated accordingly. Success was attained without periodontal intervention.

Clinical patterns among invasive pulmonary aspergillosis patients with and without recent intensive immunosuppressive therapy.

BACKGROUND AND PURPOSE: Invasive pulmonary aspergillosis (IPA) is usually an acute life-threatening infection in cancer patients receiving chemotherapy and in organ transplant recipients receiving immunosuppressive therapy. In some immunocompetent patients, IPA has a chronic and indolent clinical course. We compared the clinical patterns among IPA patients who had received recent intensive immunosuppressive therapy (RIIT) and those who had not (N-RIIT). METHODS: We reviewed the medical records of patients with a diagnosis of IPA made between 1992 and 1999. RIIT was defined as chemotherapy or high-dose corticosteroid therapy (at least 500 mg/d methylprednisolone, or equivalent, for at least 3 d) within 2 weeks before the onset of symptoms. RIIT patients were divided into those with and without malignancy. We compared clinical characteristics including age, sex, chest image patterns, diagnostic methods, culture results, treatment conditions, mortality, and recurrence rate in IPA patients: RIIT versus N-RIIT, and RIIT with and without malignancy. RESULTS: A total of 24 patients with IPA, 17 patients who had received RIIT and seven patients who had not (N-RIIT), were included. In the RIIT group, 11 patients had malignancy and six did not. No significant differences in gender, chest image patterns, diagnostic methods, and culture results were found between the RIIT and N-RIIT groups. The N-RIIT group was older and was treated significantly later after the onset of symptoms than the RIIT group (mean +/- standard deviation, SD, 89.43 +/- 129.47 vs 9.70 +/- 9.33 d, p = 0.018). Only one of the seven N-RIIT patients died, while nine of the 17 RIIT patients died (p = 0.08). Among the RIIT patients, five of the six without malignancy died, while four of the 11 patients with malignancy died. IPA recurred in seven of the eight RIIT patients, all of whom had malignancy, but in none of the six N-RIIT patients during a similar follow-up period (mean +/- SD, 16.3 +/- 18.9 vs 27.0 +/- 54.5 mo, p = 0.505). CONCLUSIONS: No differences were noted in image and culture studies between RIIT and N-RIIT IPA patients. RIIT IPA patients had acute and fulminant clinical courses, especially patients without malignancy, even though they received treatment with a mean duration of about 10 days starting from the onset of symptoms. All patients with malignancy undergoing further chemotherapy had recurrence of IPA. N-RIIT IPA patients had chronic clinical courses, a trend of lower mortality rate even with delayed diagnosis, and no recurrence.