Impact of Day 14 Peripheral Blood Chimerism after Allogeneic Hematopoietic Stem Cell Bone Transplantation on the Treatment Outcome of Non-Malignant Disease

BACKGROUND: The impact of early peripheral blood chimerism on the outcome of allogeneic hematopoietic stem cell transplantation (allo-HSCT) is unclear. We aimed to determine whether day 14 peripheral blood chimerism after allo-HSCT predicts outcomes in patients with non-malignant diseases. METHODS: Data from 56 patients who received allo-HSCT between April 2007 and March 2016 were retrospectively analyzed. Chimerism was evaluated using short-tandem repeat polymerase chain reaction, with mixed chimerism (MC) defined as greater than 1% recipient cells which was further categorized into low-level MC (> 1% and < 15% of recipient-derived cells) and high-level MC (≥ 15% of the recipient-derived cells). RESULTS: Thirty-six patients showed complete donor chimerism (CC), 14 low-level MC, and 6 high-level MC at day 14 post-transplant. The estimated 5-year event-free survival (EFS) was higher in the CC or low-level MC groups than in the high-level MC group (86.1% vs. 71.4% vs. 33.3%; P = 0.001). In BM or peripheral blood stem cell (BM/PBSC) transplants, the 5-year EFS was higher in the CC or low-level MC group than in the high-level MC group (93.1% vs. 66.7% vs. 0%; P < 0.001). However, in cord blood transplants, the 5-year OS and EFS according to the day 14 peripheral blood chimerism did not reach statistical significance. CONCLUSION: Although CC is not always necessary after allo-HSCT for non-malignant diseases, our data suggest that day 14 peripheral blood chimerism may predict outcomes in patients with non-malignant diseases who underwent BM/PBSC transplants.

Study the usefulness of ascitic fluid cholesterol level in diagnosis of malignant related ascites

Background: Dengue fever is currently the most important arthropod borne viral disease. Since occurrence of dengue infections has been an epidemic in many parts of India and complications like DHF and DSS are increasing, while at the same time the diagnosis is challenging, particularly the laboratory diagnosis is confusing, this study was conducted to evaluate the different laboratory test methods and to compare their respective efficacy, timing, advantages and disadvantages.Methods: This study was done in the Department of Microbiology in collaboration with the Department of Medicine and Pediatrics in two tertiary care medical colleges and hospitals in eastern India. Blood samples from 319 patients with clinical features suggestive of Dengue fever were included in this study. Laboratory investigations were done which included immunological assays that were performed using commercially available kits - SD dengue duo NS1Ag + Ab combo rapid test, NS1 Ag capture ELISA, IgM capture ELISA, IgG capture ELISA test for dengue and other routine tests -full blood cell count, coagulation tests, routine biochemical and lipid profile were also done. Ethical considerations were taken care of and statistical evaluations were done.Results: An increased detection of IgM antibody (46.15%) was seen in the early febrile period (1-5 days) as compared to the mid-febrile period (6-10 days), and late febrile period (6-10 days) when it is 6.89%. IgG antibody is much less in early febrile period (4.16%). Compared to mid-febrile period (24.13%), and late febrile period (62.5%). IgM antibodies were detected in 44.5% of the samples, IgG antibodies were detected in 43.5% of the samples, Rapid test was positive in 36.9% and NS1AG ELISA was detected in 43.5% of the samples in the study.Conclusions: It can be inferred from our study that for detection of dengue in the early febrile period (1-5 days), estimation of dengue-specific serum IgM is the most sensitive antibody detection method.

Rol del PET/CT con 18FDG en patología no neoplásica / Role of 18FDG PET/CT in non-malignant diseases

La Tomografía por emisión de positrones/tomografía computada (PET/CT) se ha vuelto fundamental para la evaluación oncológica. En los últimos años se ha hecho evidente su utilidad para evaluar otras patologías inflamatorias no neoplásicas, las cuales pueden presentar aumento del metabolismo medible. El PET/CT tiene la ventaja de poder detectar enfermedades incluso cuando no tienen un correlato en las imágenes morfológicas, permitiendo además localizar de manera precisa estas alteraciones. Entre estas patologías se encuentran el estudio de fiebre de origen desconocido, enfermedades inflamatorias, enfermedades del tejido conectivo, vasculitis y también en el seguimiento y diagnóstico de algunas patologías infecciosas. Se realizará una revisión en la literatura de la utilidad del PET/CT en estas patologías complementada con casos clínicos.

A histopathological study of non-malignant breast lesions.

Background: The study was undertaken to know the various histopathological patterns of non-malignant breast lesions and its frequency of occurrence. A wide spectrum of malignant, benign and non-neoplastic diseases can affect the breast. Though, the carcinoma of the breast is fairly common, non-malignant breast lesions constitute a separate group which poses diagnostic difficulty to both clinicians and pathologists as it simulates malignancy clinically, morphologically and microscopically. Methods: The current study was carried out in a tertiary care institute in West Maharashtra, India. Cases included in this study were of non-malignant breast lesions which included excisional and incisional biopsies and lumpectomy specimens from surgical department at tertiary hospital. Results: 540 non-malignant breast lesions were studied out of total 759 breast biopsies, in the period of six years. The incidence of non-malignant breast lesions was found to be 71.15% of all breast lesions. The commonest non-malignant breast lesion was fibroadenoma, seen in 216 (40%) cases; followed by fibrocystic disease, seen in 177 (32.78%) cases. Conclusions: Thus, we came to a conclusion that benign breast lesions are complex of inflammatory lesions, tumour and pseudo tumour like hamartoma. Thus even if they may cause lump or not, the breast lesions remain enigma.

Usefulness of Ascitic Fluid Cholesterol and Protein in the Differential Diagnosis of Ascites in Nigeria: Comparison with Conventional Cytology.

Aim: This study was done to assess and evaluate the diagnostic accuracy of cholesterol and protein in differentiating ascites into malignant and non-malignant group in comparison with cytology. Study Design: A cross sectional study to determine the correlation between ascitic fluid cholesterol and protein and malignant and non-malignant ascites. Place and Duration of Study: This study was carried out at the clinics of gastroenterology surgery, and obstetrics/gynecology at the Lagos University Teaching Hospital (LUTH), between August 2011 and July 2013. Methodology: A total of 75 consecutive patients of Nigerian origin with ascites (37 malignant and 38 non-malignant) were studied for total cholesterol and total protein concentration in ascites. Also, cytology was done for all the 75 samples of ascitic fluid. Statistical analyses were carried out using SPSS software (version 15.0), and the level of significance set at p<0.05 and p<0.001. Results: The ascitic fluid cholesterol and protein levels in malignant ascites were higher (values of 103.10±30.00 mg/dL for cholesterol and 38.72±18.00 g/L for protein respectively) than in nonmalignant ascites (values of 33.20±22.00 mg/dL for cholesterol and 30.21±15.00 g/L for protein). The p value for cholesterol was less than 0.001. Cytology had sensitivity, specificity, positive predictive value, negative predictive value and overall diagnostic accuracy of 56.8%, 100%, 100%, 70.4%, and 78.6% respectively. Using a cut-off limit of 72.7 mg/dL, cholesterol had sensitivity, specificity, positive predictive value, negative predictive value and overall diagnostic accuracy of 94.6%, 94.7%, 94.6%, 94.7% and 94.7% respectively. Ascitic fluid total protein had sensitivity, specificity, positive predictive value, negative predictive value and overall diagnostic accuracy of 37.8%, 86.8%, 73.7%, 58.9%, and 62.7% respectively. Cholesterol was more sensitive than protein and cytology in the differentiating malignant from non-malignant ascites. Conclusion: It was concluded that measurement of cholesterol in ascitic fluid can differentiate between malignant and non-malignant ascites, and can supplement cytology in the differential diagnosis of ascites.

The Relevance of Ascitic Lactate Dehydrogenase (LDH) and Serum Ascites Albumin Gradient (SAAG) in the Differential Diagnosis of Ascites among Patients in a Nigerian Hospital.

Aim: The study aimed to determine the diagnostic values for lactate dehydrogenase (LDH) and serum ascites albumin gradient (SAAG) with maximum sensitivity and minimum false positivity so as to differentiate malignancy-related ascites from non-malignant ascites in South West region of Nigeria. Study Design: This is a cross sectional study to determine the correlation between ascitic fluid LDH and SAAG and malignant and non-malignant ascites. Place and Duration of Study: This study was carried out at the clinics of gastroenterology, surgery, and obstetrics/gynecology at the Lagos University Teaching Hospital (LUTH), between August 2011 and July 2013. Methods: A total of 75 patients with ascites admitted into Lagos University Teaching Hospital (LUTH) from 2011 to 2013 were enrolled for the study. Thirty seven (7males, 30 females) had malignancy-related ascites while 38(18 males, 20 females) had non-malignant ascites. Levels of LDH and SAAG were determined in all patients with ascites. Statistical analysis was performed using SPSS software application (version 15.0) and p˂0.05 was considered statistically significant and results expressed as mean ± standard deviation. Results: A total of 75 patients were recruited for the study. Twenty-five of them (33.3%) were males while 50(66.7%) were females. The mean age for both sexes was 59.03±13.54 years. Using Receiver Operator Characteristic (ROC) curve, cut-off levels were 11.5 for SAAG and 310 IU/l for LDH. These cut-offs divided the malignant from the non-malignant group. Higher levels of ascitic LDH were seen in the malignant group (900.67±918.45 IU/l) when compared to the non-malignant group (199.29±194.53 IU/l). This was statistically significant (P<0.05). The diagnostic accuracy of LDH was 90.7%. SAAG was lower in the malignant (6.74±4.84 g/L) group when compared to the non-malignant (13.56±7.50 g/L). This was also statistically significant (P<0.05). The diagnostic accuracy of SAAG was 73.3%. Conclusion: It was concluded that measurement of ascitic fluid LDH and SAAG were relevant in differentiating malignant from non-malignant ascites. The determined cut-off values for LDH and SAAG in this study provides the distinctive differential diagnosis between malignant and nonmalignant ascites. Routine analysis of serum and ascitic fluid albumin and LDH will resolve the problem of malignant and non-malignant ascites especially in low-resource areas or in the developing world.

Ascitic Fluid Fibronectin: A Marker to Differentiate Between Malignant and Non-malignant Ascites.

Background and Aims: So far, the differentiation between malignant and non-malignant ascites by laboratory parameters has not been fully achieved yet. Fibronectin is a glycoprotein which plays an important role in cell adhesion, growth, migration, and differentiation. The aim of the study was to assess the accuracy of fibronectin for the diagnosis of malignant ascites and to compare it with conventional use of cytology. Study Design: A cross sectional study to determine the correlation between ascitic fluid fibronectin and malignant and non-malignant ascites. Place and Duration of Study: This study was carried out at the clinics of gastroenterology, surgery, and obstetrics/gynecology at the Lagos University Teaching Hospital (LUTH), between August 2011 and July 2013. Methods: Ascitic fluid and serum samples from 75 patients were taken. 37 of them (7 males and 30 females) had malignancy-related ascites (Group 1), while the other 38 (18 males and 20 females) had non-malignant ascites (Group 2) respectively. These were analysed for fibronectin, lactate dehydrogenase (LDH), total protein, and albumin. Cytology was also done for all ascitic fluid samples. Results: Mean values of ascitic fluid fibronectin and LDH were higher in malignancy-related ascites (97.5 μg/ml, and 900.60 IU/L) respectively than in non-malignant ascites (47.7 μg/ml, and 199.31 IU/L) respectively (P less than 0.001). Ascitic fluid fibronectin with a cut-off value of 73 μg/ml gave the best diagnostic accuracy with a sensitivity and specificity of 94.7% and 94.6% respectively, while ascitic fluid LDH with a cut-off value of 310 IU/L gave diagnostic accuracy with a sensitivity and specificity of 97.3% and 84.2% respectively. The mean total protein level in the malignant group was 38.72±18.00 g/L and 30.21±15.00 g/L for the non-malignant group. The mean albumin levels were 28.08±10.32 g/L and 31.23±10.01 g/L for the malignant and non-malignant groups respectively. For both total protein and albumin, the P value was statistically insignificant. In this study, cytology yielded a sensitivity of 56.8% and a specificity of 100%. Conclusion: The results of this study suggest that fibronectin concentration in ascitic fluid may be useful in differentiating malignant from non-malignant ascites and could supplement cytology in the differential diagnosis of ascites. Further studies are needed to confirm these results.

End-of-life care by expert clinical nurses for non-malignant chronic illness patients in genelral hospitals

This study clarified practices in end-of-life care for non-malignant chronic illness patients by expert nurses in general hospitals. Interviews with 7 chronic illness specialist nurses on practice cases were conducted, and final labels were elicited using a qualitative synthesis method（KJ method）. As patients’ conditions deteriorated, nurses defined the necessary interactions to support patients’ decision-making for living their own way of life and accompany patients and families based on their experience, and using patients’ restoration of self-esteem, sense of satisfaction, and acceptance as indices. In general hospitals, measures to cope with pain for patients not receiving life-prolonging treatment were insufficient;and while it was difficult to agree on care between medical professionals and to maintain care in other facilities, expert nurses grasped patients’ wishes on a daily basis and made arrangements for them to permeate through family and community care systems. In end-of-life care in treatment settings, it is necessary to be supportive so that the family and medical professionals can continue the patient’s care. Medical professionals who have been involved from the initial diagnosis stage need to improve their awareness and support skills as medical professionals to be involved purposefully from an early stage to the final stage.

Clinical implications of chimerism after allogeneic hematopoietic stem cell transplantation in children with non-malignant diseases

BACKGROUND: The effects of chimerism on outcomes following allogeneic hematopoietic stem cell transplantation (HSCT) are unclear and may differ between diseases. We retrospectively evaluated the association between chimerism and transplant outcomes in children with nonmalignant diseases. METHODS: Chimerism was evaluated using short-tandem repeat polymerase chain reaction (STR-PCR) in 48 patients, with mixed chimerism (MC) defined as greater than 1% recipient cells. RESULTS: The only variable exerting a significant influence on patients' chimerism status was the number of infused CD34+ cells. MC was detected in 23 transplants (9 showing transient MC; 10 with sustained low levels [30%]). The degree of STR-PCR at 28 days after HSCT was significantly higher in patients with high-level MC than those with transient or low-level MC. All patients with transient or low-level MC successfully maintained engraftment and showed a clinical response to HSCT, whereas 2 of the 4 patients with high-level MC experienced graft failure. The incidences of grades II-IV acute and chronic graft-versus-host disease (GVHD) were significantly higher in patients with complete donor chimerism (CC) than MC. We observed no significant survival differences between CC and MC groups. However, the survival rate was lower in patients with high MC than those with low-level or transient MC (P=0.03). CONCLUSION: In non-malignant diseases, MC may indicate a tolerant state with a decreased incidence of GVHD. However, high-level MC may signify an increased risk of graft failure and a lower survival rate.