• Tuberculosis and Respiratory Diseases
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• v.55 no.5
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• pp.449-458
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• 2003

Background : The poor prognostic factors of far-advanced pulmonary tuberculosis(FAPTB) are lymphocytopenia in the peripheral blood(PB)(< $1,000/mm^3$) and $T_4$-cell count ${\leq}500/mm^3$. However, the cause of PB lymphocytopenia in FAPTB is unclear. The aim of this study was to analyze the lymphocyte proportion and cytokines of the bone marrow(BM) in FAPTB patients with peripheral lymphocytopenia in order to clarify whether the limiting step of the lymphocytopenia occurs in production, differentiation, or circulation. Methods : This study included patients with FAPTB between August 1999 and August 2002 who visited Gachon Medical School Gil Medical Center. The exclusion criteria were old age(${\geq}65years$), cachexia or a low body weight, shock, hematologic diseases, or BM involvement of tuberculosis. The distributions of cells in PB and BM were analyzed and compared to the control group. The interleukin(IL)-2, IL-7, IL-10, TNF-${\alpha}$, Interferon-${\gamma}$, and TGF-${\beta}$ levels in the BM were measured by ELISA. Result : Thirteen patients(male : female=9:4) were included and the mean age was $42{\pm}12$years. The proportion and count of the lymphocytes in the PB were significantly lower in the FAPTB group ($7.4{\pm}3.0%$, $694{\pm}255/mm^3$ vs. $17.5{\pm}5.8%$, $1,377{\pm}436/mm^3$, each p=0.0001 and 0.002). The proportion of immature lymphocyte in the BM showed a decreasing trend in the FAPTB group($9{\pm}4%$ vs. $12{\pm}3%$, p=0.138). The IL-2($26.0{\pm}29.1$ vs. $112.2{\pm}42.4pg/mL$, p=0.001) and IL-10($3.4{\pm}4.7$ vs. $12.0{\pm}8.0pg/mL$, p=0.031) levels in the BM were significantly lower in the FAPTB group than those in control. The levels of the other cytokines in FAPTB group and control were similar. Conclusion : These results suggest that the cause of lymphocytopenia in PB is associated with a abnormality IL-2 and IL-10 production in the BM. More study will be needed to define the mechanism of a decreased reservoir in BM.

• Pediatric Infection and Vaccine
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• v.23 no.1
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• pp.31-39
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• 2016

Purpose: The aim of this study was to investigate the prognostic factors for Pneumocystis jirovecii pneumonia (PCP) and to evaluate the influence of PCP prophylaxis in pediatric patients. Methods: From January 2002 to April 2015, patients aged <18 years with a diagnosis of confirmed PCP at our institute were reviewed retrospectively. Clinical characteristics and outcomes were compared according to the groups with or without PCP prophylaxis. Risk factors associated with PCP-related death were analyzed by logistic regression analysis. Results: During study period, a total of 24 patients were diagnosed with PCP by immunofluorescence assay and/or PCR. The median age of the patients was 5 years (range, 3 months-18 years) and 23 (96%) had immunocompromised conditions including hematologic disorders with or without hematopoietic stem cell transplantation (n=15), solid organ transplantation (n=4), and primary immune deficiency (n=4). Most common presenting symptoms were tachypnea and cough (92%, each). At the time of diagnosis, 79% (19/24) and 25% (6/24) suffered from respiratory failure and multi-organ dysfunction syndrome (MODS), respectively. Mechanical ventilation was required in 8 (33%) patients and 5 (21%) patients died of PCP. Multivariate analysis showed that MODS at initial presentation was an indicator of poor prognosis (OR, 17.1 [95% CI 1.13-257.67]; P=0.04). Compared to the patients without PCP prophylaxis, the frequency of MODS at diagnosis, need for mechanical ventilation and length of hospital days were significantly less common in the children who received PCP prophylaxis. Conclusions: MODS at presentation was a significant predictor for poor outcome and PCP prophylaxis could alleviate the clinical courses of pediatric PCP. Prospective study will be mandatory to determine the risk factors for development and deterioration of PCP in children.

• The Korean Journal of Nuclear Medicine
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• v.37 no.6
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• pp.428-436
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• 2003

Purpose: Increased periarticular uptake could be associated with peripheral bone marrow expansion in cancer patients with axial bone marrow metastasis. We compared bone scan and bone marrow scan to investigate whether the increased whole body count in patients with increased periarticular uptake on bone scan is useful in the diagnosis of axial marrow metastasis, and evaluate the role of additional bone marrow scan in these cases. Materials and methods: Twelve patients with malignant diseases who showed increased periarticular uptake on bone scan were included. Whole body count was measured on bone scan and it is considered to be increased when the count is more than twice of other patients. Bone marrow scan was taken within 3-7 days. Results: Five hematologic malignancy, 3 stomach cancer, 2 breast cancer, 1 prostate cancer and 1 lung cacner were included. All three patients with increased whole body count on bone scan showed axial marrow suppression and peripheral marrow expansion. Eight of 9 patients without increased whole body count showed axial marrow suppression and peripheral marrow expansion. One turned out to be blastic crisis of chronic myelogeneous leukemia, and seven showed normal axial marrow with peripheral marrow expansion in chronic anemia of malignancy. The last one without increased whole body count showed normal bone marrow scan finding. Conclusion: Increased whole body count on bone scan could be a clue to axial bone marrow metastasis in cancer patients with increased periarticular uptake, and bone marrow scan is a valuable method for differential diagnosis in these cases.

• Childhood Kidney Diseases
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• v.13 no.2
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• pp.130-137
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• 2009

Purpose : Stem cell transplantation (SCT) has gained worldwide acceptance as a treatment for hematologic disorders. This study was performed to evaluate the clinical characteristics and outcomes of the acute kidney injury after SCT in children. Methods : The records of 53 patients who were treated with SCT at the pediatric department of Yeungnam University Hospital between January, 1996 and April, 2009 were used as subjects. Their were divided into two groups ; 'Early renal insufficiency' (ERI, n=18) and 'Non-early renal insufficiency' (NERI, n=35). ERI had greater than 25% of drop in GFR after SCT. Results: Total 53 patients were analyzed. In cord blood SCT (n=11), ERI was 4 (36.4%) and NERI was 7 (63.6%). In bone marrow SCT (n=16), ERI was 8 (50.0%) and NERI was 8 (50.5%). In autologous peripheral blood SCT (n=26), ERI was 6 (23.1%) and NERI was 20 (76.9%). There is no difference in both groups according to kinds of SCT. GVHD was developed in 22 patients, and there is no difference in each group. Twenty two of 53 patients died. ERI was 12 (66.7%) and NERI was 10 (28.6%). Acute renal failure is most important cause of the deaths. Conclusion : Out of 53 pediatric patients who were treated with SCT, 18 patients had greater than 25% of drop in GFR. There is no difference in both groups according to kinds of SCT. GVHD was found in 22 patients and there is no relation between GVHD development and acute kideney injury.

• Clinical and Experimental Pediatrics
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• v.45 no.4
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• pp.489-497
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• 2002

Purpose : The objectives of this study were to investigate the causes of chronic cough and to establish the appropriate diagnostic approach to chronic cough in children. Methods : One hundred and thirty two cases of chronic cough were prospectively evaluated. They visitors to pediatric chronic cough clinics at Kang-nam saint Mary's Hospital of Catholic University from August 2000 to July 2001 for 12 months. Careful history taking by questionnaire, physical examination, radiologic studies of chest and sinus, hematologic and immunologic studies, allergic skin tests, and methacholine challenge tests were performed. Color doppler(CD) ultrasonography were performed and compared with simultaneous 24 Hr. esophageal pH monitoring to diagnose gastroesophageal reflux disease(GERD). Results : Age distributions were demonstrated that nine in infants, 82 in early childhood, 38 in late childhood, and three in adolescence. Common causes of chronic cough were bronchial asthma in 40 cases, chronic sinusitis in 22 cases, GERD in seven cases, bronchial asthma combined with sinusitis in 28 cases, bronchial asthma combined with GERD in 14 cases, psychogenic cough in two. cases, foreign body in one case, chronic bronchitis in one case, and bronchiolitis in one case. Comparing with 24 Hr. pH monitoring, sensitivity, specificity, positive predictive value and negative predictive values of CD ultrasonography were 88%, 69%, 85 %, and 73% respectively. Conclusion : The most common causes of chronic cough in children were bronchial asthma, sinusitis and GERD in order. We suggest that CD ultrasonography can be used as a good, convenient screening method for patients with suspected GERD in outpatient settings.

• Clinical and Experimental Pediatrics
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• v.52 no.10
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• pp.1153-1160
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• 2009

Purpose:To evaluate the risk factors for mortality and prognostic factors in pediatric hemato-oncology patients admitted to the pediatric intensive care unit (PICU). Methods:We retrospectively reviewed the medical records of pediatric hemato-oncology patients admitted at the PICU of the Asan Medical Center between September 2005 and July 2008. Patients admitted at the PICU for perioperative or terminal care were excluded. Results:Total 88 patients were analyzed. Overall ICU mortality rate was 34.1%. Mean age at PICU admission was $7.0{\pm}5.7$ years and mean duration of PICU stay was $18.1{\pm}22.2$ days. Hematologic diseases contributed to 77.3% of all the primary diagnoses, and the primary cause of admission was respiratory failure (39.8%). The factors related to increased mortality were C-reactive protein level (P<0.01), ventilation or dialysis requirement (P<0.01), and hematopoietic stem cell transplantation (P<0.05). In all, 3 scoring systems were investigated [Number of Organ System Failures (OSF number), the Pediatric Risk of Mortality III (PRISM III) score, and the Sequential Organ Failure Assessment (SOFA) score]; higher score correlated with worse outcome (P<0.01). The Oncological Pediatric Risk of Mortality (O-PRISM) scores of the 21 patients who had received hematopoietic stem cell transplantation were higher among the non-survivors, but not statistically significant (P=0.203). Conclusion:The PRISM III and SOFA scores obtained within 24 hours of PICU admission were found to be useful as early mortality predictors. The highest OSF number during the PICU stay was closely related to poor outcome.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.4
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• pp.1811-1815
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• 2014

Background: In clinical trials with no upper age limit, the proportion of older patients is usually small, probably reflecting the more conservative approach adopted by clinicians when treating the elderly. An exploratory analysis of elderly patients in the RECORD-1 Trial showed that patients ${\geq}$ 65 y.o. had superior median PFS than overall RECORD-1 population (5.4 months and 4.9 months, respectively). We investigated the efficacy, relative benefit and safety of Everolimus (EVE) as sequential therapy after failure of VEGFr-TKI therapy for older patients with metastatic renal cell cancer (mRCC), in daily practice. Materials and Methods: 172 consecutive IRB approved patients with mRCC (median age 65, M:F 135/37, 78% clear cell) who received salvage EVE at 39 tertiary institutions between October 2009 and August 2011 were included in this analysis. Some 31% had progressed on sunitinib, 22% on sorafenib, 1% on axitinib, 41% on sequential therapy, and 5% had received other therapy. Patients with brain metastases were not included and 95% of the patients had a ECOG (Eastern Cooperative Oncology Group) performance status (PS) of 0 or 1. Previous radiotherapy was an exclusion criterion, but prior chemotherapy was permitted. Adequate organ function and hematologic parameters were mandatory. EVE administration was approved by the institutional review board at each participating institution and signed informed consent was obtained from all patients. Results: Median time of the whole cohort to last follow-up was 3.5 months (range 0.4-15.2 months). Forty four percent were continuing to take EVE at last followup. There were 86 (50%) patients ${\geq}$ 65 y.o. and 86 (50%) <65 y.o. The percentage of patients who showed PR/SD was higher in the older group than in the younger one (5.9%/61.2% vs 1.2%/46.5%, respectively). Median survival of older patients was also significantly longer (3.5 +/- 0.31 vs 3.1 +/- 0.34, hazard ratio=0.45, CI; 0.255-0.802). Analysis using Cox regression model adjusted for gender, PS, number of metastases, site of metastases, histology, smoking history and age detected an association between age and PFS (p=0.011). The frequency of adverse events in elderly patients treated with EVE was no greater than that in younger patients, although such toxicity may have had a greater impact on their quality of life. Conclusions: Older patients should not generally be excluded from accepted therapies (mTOR inhibitors after failure of VEGFr-TKI therapy) for mRCC.

• Pediatric Infection and Vaccine
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• v.12 no.1
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• pp.75-85
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• 2005

Purpose : Fungal infection is one of the important causes of morbidity and mortality in patients with hematologic malignancies. Amphotericin B(ABV) and itraconazole(ITZA) have been used as the standard empirical antifungal therapy in neutropenic patients with acute leukemia who have persistent fever that does not respond to antibiotic therapy. ABV is an antifungal drug associated with side effects such as fever and chills, symptoms which may be mediated by pro-inflammatory cytokines such as interleukin-$1{\beta}$(IL-$1{\beta}$) and tumor necrosis factor-${\alpha}$(TNF-${\alpha}$). We assessed modulation of these pro-inflammatory cytokines as well as the anti-inflammatory cytokines(IL-4, IL-1Ra) by ABV and ITZA. Methods : From March 2004 to February 2005, a total of 30 episodes from acute leukemia patients with febrile neutropenia were analyzed for this study. They were randomly allocated to receive intravenous ABV or ITZA for 14 days. Clinical responses were evaluated at the completion of therapy, and cytokine IL-$1{\beta}$, TNF-${\alpha}$, IL-4, and IL-1Ra were measured for determination to know the correlation between two antifungal agents and inflammatory cytokines. Results : Empirical antifungal agents were given to 37 patients(ABV 20, ITZA 17), and 30 patients(ABV 15, ITZA 15) were evaluable for efficacy. White blood cell and absolute neutrophil count in the group treated with ITZA increased early days of treatment, so the duration of neutropenia in ITZA group is shorter. Serum creatinine level is lower in ITZA group than in ABV group but this is not statistically significant. There was no significant difference in response rate between two groups. The IL-$1{\beta}$ was increased in ABV treatment group and the ratio of IL-1Ra/IL-$1{\beta}$ is markedly decreased in ABV treatment group while increased in ITZA group. Conclusion : ITZA and ABV have at least equivalent efficacy as empirical antifungal therapy in neutropenic children with acute leukemia. However ITZA is associated with significantly less toxicity in clinical and molecular aspects.

• Pediatric Infection and Vaccine
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• v.16 no.1
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• pp.61-72
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• 2009

Purpose : We evaluated the clinical features of Norovirus gastroenteritis compared with Rotavirus gastroenteritis in hospitalized children. Methods : We detected causative agents in 3,261 samples of children hospitalized with gastroenteritis symptoms at a single center of pediatrics between 2005 and 2006. Among 266 and 303 samples which tested positive for Norovirus and Rotavirus, we selected 73 and 182 samples of children with relatively pure gastroenteritis symptoms and retrospectively analyzed the corresponding medical records. Results : The male-to-female ratio of the Norovirus (+) and Rotavirus (+) groupswas 1.43:1 and 1.56:1 both groups were predominantly in males. The mean age of the Norovirus (+) and Rotavirus (+) groups was 36.7 and 24.4 months, respectively the children in the former group were older than the children in the latter group. The incidence in the Norovirus (+) group was more concentrated in the winter. The symptoms in the Norovirus (+), in decreasing order, included vomiting, diarrhea, and fever. The duration of vomiting, diarrhea, and fever was 2.1, 1.2, and 1.2 days. The maximum number of episodes of vomiting and diarrhea per day was 3.5 and 4.5, respectively. The severity score was 10.16. The symptoms inthe Rotavirus (+) group, in decreasing order, included diarrhea, vomiting, and fever. The duration of diarrhea, vomiting, and fever was 2.2, 4.3, and 2.2 days, respectively. The maximum number of episodes of vomiting and diarrhea per day was 3.3 and 6.5, respectively. The severity score was 11.9. The severity in the Norovirus (+) group was somewhat lower than the Rotavirus (+) group. The younger the child, the more severe the symptoms in the Norovirus (+) group. There was no difference between mono-and co-infection in severity and between the two groups regarding the hematologic findings. Conclusion : Based on the findings reported herein, additional studies about prophylaxis, as well as the epidemiology and clinical features of pediatric Norovirus gastroenteritis, are required.