105 results on '"Kaddu-Mulindwa D"'
Search Results
2. Hypophosphatemia after high-dose iron repletion with ferric carboxymaltose and ferric derisomaltose—the randomized controlled HOMe aFers study
- Author
-
Emrich, I. E., Lizzi, F., Siegel, J. D., Seiler-Mussler, S., Ukena, C., Kaddu-Mulindwa, D., D’Amelio, R., Wagenpfeil, S., Brandenburg, V. M., Böhm, M., Fliser, D., and Heine, G. H.
- Published
- 2020
- Full Text
- View/download PDF
3. PB2104: DOSE-DENSE CHEMOTHERAPY WITH R-CHOP-14 IN OLDER ADULTS AGED ≥80 YEARS WITH DIFFUSE LARGE B-CELL LYMPHOMA
- Author
-
Christofyllakis, K., primary, Dilbaz, Z. G., additional, Denker, S., additional, Ankermann, C., additional, Kunte, A., additional, Poeschel, V., additional, Bewarder, M., additional, Kaddu-Mulindwa, D., additional, Stilgenbauer, S., additional, Thurner, L., additional, Na, I.-K., additional, and Bittenbring, J.-T., additional
- Published
- 2022
- Full Text
- View/download PDF
4. LIVER STIFFNESS MEASUREMENTS IN EMERGENCY TRIAGE PREDICT INPATIENT HEALTH CARE UTILIZATION
- Author
-
Kaddu-Mulindwa, D, additional, von Martial, M, additional, Thiel-Bodenstaff, A, additional, Lesan, V, additional, Ewen, S, additional, Mahfoud, F, additional, Lammert, F, additional, and Krawczyk, M, additional
- Published
- 2021
- Full Text
- View/download PDF
5. FDG PET/CT to detect bone marrow involvement in the initial staging of patients with aggressive non-Hodgkin lymphoma : results from the prospective, multicenter PETAL and OPTIMAL > 60 trials
- Author
-
Kaddu-Mulindwa, D., Altmann, B., Held, G., Angel, S., Stilgenbauer, S., Thurner, L., Bewarder, Moritz, Schwier, M., Pfreundschuh, Michael, Löffler, Markus, Menhart, Karin, Grosse, Jirka, Ziepert, Marita, Herrmann, Ken, Dührsen, Ulrich, Hüttmann, Andreas, Barbato, Francesco, Pöschel, Viola, and Hellwig, Dirk
- Subjects
Medizin - Published
- 2020
6. Rolle der FDG-PET/CT zur Erkennung eines Befalls des Knochenmarkes (KM) beim initialen Staging des aggressiven Non-Hodgkin-Lymphoms (NHL)
- Author
-
Grosse, J, additional, Altmann, B, additional, Kaddu-Mulindwa, D, additional, Held, G, additional, Ziepert, M, additional, Menhart, K, additional, Angel, S, additional, Stilgenbauer, S, additional, Pfreundschuh, M, additional, Pöschel, V, additional, and Hellwig, D, additional
- Published
- 2020
- Full Text
- View/download PDF
7. SAMD14/NEURABIN-I AS BCR-ANTIGENS OF PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA
- Author
-
Thurner, L., primary, Bewarder, M., additional, Fadle, N., additional, Regitz, E., additional, Poeschel, V., additional, Ziepert, M., additional, Schuck, R., additional, Altmeyer, S., additional, Kemele, M., additional, Bock, T., additional, Schormann, C., additional, Walter, S., additional, Szczepanowski, M., additional, Klapper, W., additional, Monoranu, C., additional, Rosenwald, A., additional, Moeller, P., additional, Kim, Y., additional, Buslei, R., additional, Kaddu-Mulindwa, D., additional, Neumann, F., additional, Roemer, K., additional, Bohle, R., additional, Illerhaus, G., additional, Schorb, E., additional, Schaefer, H., additional, Hansmann, M.L., additional, Hartmann, S., additional, Held, G., additional, Stilgenbauer, S., additional, Murawski, N., additional, Pfreundschuh, M., additional, and Preuss, K.D., additional
- Published
- 2019
- Full Text
- View/download PDF
8. Safety and feasibility of electrical muscle stimulation in patients undergoing autologous and allogeneic stem cell transplantation or intensive chemotherapy
- Author
-
Bewarder, M., primary, Klostermann, A., additional, Ahlgrimm, M., additional, Bittenbring, J. T., additional, Pfreundschuh, M., additional, Wagenpfeil, S., additional, and Kaddu-Mulindwa, D., additional
- Published
- 2018
- Full Text
- View/download PDF
9. 'Ten Commandments' for the Appropriate use of Antibiotics by the Practicing Physician in an Outpatient Setting
- Author
-
Levy-Hara, G, Amábile-Cuevas, CF, Gould, I, Hutchinson, J, Abbo, L, Saxynger, L, Vlieghe, E, Lopes Cardoso, FL, Methar, S, Kanj, S, Ohmagari, N, Harbarth, S, Aiken, A, Alnimr, A, Bavestrello, L, Carlet, J, Dreser, A, Essack, S, Hsueh, P-R, Ismail, N, Kaddu-Mulindwa, D, Kolmos, HJ, Mochizuki, T, Ndewga, L, Odio, C, Peredo, MA, Vega, S, Viswanathan, R, and Wertheim, H
- Subjects
Microbiology (medical) ,medicine.medical_specialty ,Evidence-based practice ,antibiotic resistance ,medicine.drug_class ,Antibiotics ,lcsh:QR1-502 ,antibiotic stewardship ,Appropriate use ,Microbiology ,lcsh:Microbiology ,generic antibiotics ,Antibiotic resistance ,medicine ,Short course ,guidelines ,Medical prescription ,Intensive care medicine ,antibiotic stewarship ,treatment compliance ,self-prescription ,business.industry ,Perspective Article ,Antibiotic Stewardship ,business ,Self-medication - Abstract
A multi-national working group on antibiotic stewardship, from the International Society of Chemotherapy, put together ten recommendations to physicians prescribing antibiotics to outpatients. These recommendations are: (1) use antibiotics only when needed; teach the patient how to manage symptoms of non-bacterial infections; (2) select the adequate ATB; precise targeting is better than shotgun therapy; (3) consider pharmacokinetics and phar-macodynamics when selecting an ATB; use the shortest ATB course that has proven clinical efficacy; (4) encourage patients' compliance; (5) use antibiotic combinations only in specific situations; (6) avoid low quality and sub-standard drugs; prevent prescription changes at the drugstore; (7) discourage self-prescription; (8) follow only evidence-based guidelines; beware those sponsored by drug companies; (9) rely (rationally) upon the clinical microbiology lab; and (10) prescribe ATB empirically - but intelligently; know local susceptibility trends, and also surveillance limitations. © 2011 Lev-Hara, Amábile-Cuevas, Gould, Hutchinson, Abbo, Saxynger, Vlieghe, Cardoso, Methar, Kanj, Ohmagari, HarbarthandISC-ASW Group.
- Published
- 2011
- Full Text
- View/download PDF
10. Prevalence and immediate outcome of candida colonized preterm neonates admitted to Special Care Unit of Mulago Hospital, Kampala Uganda
- Author
-
Abdallah, Y, primary, Kaddu-Mulindwa, D, additional, Nankunda, J, additional, and Musoke, PM, additional
- Published
- 2015
- Full Text
- View/download PDF
11. Campylobacter spp among Children with acute diarrhea attending Mulago hospital in Kampala - Uga
- Author
-
Msahan, SE, Joloba, M, Kakooza, A, and Kaddu-Mulindwa, D
- Subjects
Campylobacter spp, Prevalence, Acute diarrhea - Abstract
Background: Campylobacter infections occur worldwide. A recent study in Kampala, Uganda, found that 87% of broiler chickens had Campylobacter jejuni; these are potential source of human infection. Isolation rate in developing countries is between 5-35%. This study aimed at finding prevalence of children with campylobacter infection among children with acute diarrhea attending Mulago hospital. Objective: The objective was to establish the proportion of children infected with Campylobacter spp among children with acute diarrhea at Mulago hospital. Methods: A crossectional study from July to October 2005 was conducted involved 226 children with sampling was done a total of 226 stool specimens were obtained and cultured on selective media. Identification was done using biochemical test and susceptibility using standard discs diffusion method.Results: Campylobacter spp were isolated in 21 (9.3%) of 226 stool specimens analyzed. Campylobacter jejuni 17 (80.9%), Campylobacter lari 2 (9.5%), Campylobacter coli 1 (4.5%) and Campylobacter jejuni/coli 1(4.5%). All Campylobacter isolates were sensitive to erythromycin, and 20% had intermediate resistance to Ampicillin. Conclusion: Campylobacter spp are prevalent among children with acute diarrhea in Kampala- Uganda. A large multicenter study should be undertaken so that the extent of campylobacter infection in our setting can be established.Keywords: Campylobacter spp, Prevalence, Acute diarrheaAfrican Health Sciences 2009; 9(3):201-205
- Published
- 2009
12. Campylobacter spp among Children with acute diarrhea attending Mulago hospital in Kampala - Uganda
- Author
-
Mshana, SE, Joloba, M, Kakooza, A, and Kaddu-Mulindwa, D
- Subjects
Diarrhea ,Male ,Infant ,Campylobacter ,Articles ,Microbial Sensitivity Tests ,Anti-Bacterial Agents ,Feces ,Age Distribution ,Cross-Sectional Studies ,Child, Preschool ,Acute Disease ,Campylobacter Infections ,Drug Resistance, Bacterial ,Prevalence ,Humans ,Female ,Uganda - Abstract
Campylobacter infections occur worldwide. A recent study in Kampala, Uganda, found that 87% of broiler chickens had Campylobacter jejuni; these are potential source of human infection. Isolation rate in developing countries is between 5-35%. This study aimed at finding prevalence of children with campylobacter infection among children with acute diarrhea attending Mulago hospital.The objective was to establish the proportion of children infected with Campylobacter spp among children with acute diarrhea at Mulago hospital.A crossectional study from July to October 2005 was conducted involved 226 children with acute diarrhea. Serial sampling was done a total of 226 stool specimens were obtained and cultured on selective media. Identification was done using biochemical test and susceptibility using standard discs diffusion method.Campylobacter spp were isolated in 21 (9.3%) of 226 stool specimens analyzed. Campylobacter jejuni 17 (80.9%), Campylobacter lari 2 (9.5%), Campylobacter coli 1 (4.5%) and Campylobacter jejuni/coli 1(4.5%). All Campylobacter isolates were sensitive to erythromycin, and 20% had intermediate resistance to Ampicillin.Campylobacter spp are prevalent among children with acute diarrhea in Kampala- Uganda. A large multicenter study should be undertaken so that the extent of campylobacter infection in our setting can be established.
- Published
- 2009
13. Intravascular catheter related infections in children admitted on the paediatric wards of Mulago hospital, Uganda
- Author
-
Nahirya, P, Byarugaba, J, Kiguli, J, and Kaddu-Mulindwa, D
- Abstract
Introduction: Worldwide use of intravascular catheters (IVC) has been associated with both local and systemic infections. No studies have been done in the sub-Saharan region on IVC related infections. Objective: To determine the prevalence, causative organisms and their antimicrobial susceptibility pattern and the factors associated with infections related to short term peripheral venous catheters in children admitted to the general paediatric wards in Mulago Hospital, Uganda. Methods: A cross-sectional study of 391 children aged one day to 12 years, on Jelliffe ward in Mulago Hospital, who had short peripheral venous intravascular catheters uncoated with no antibiotic or antiseptic, was done. Social demographic characteristics, anthropometry, clinical examination including the catheter site were determined at enrollment. The children had their blood, catheter tip and hub samples taken off for culture and sensitivity as well as complete blood counts. The data collected was entered using EPIINFO and analysed with SPSS packages. Results: Out of the 391 short term peripheral venous catheters collected, 20.7% catheter tips and 11.3% catheter hubs were colonised. Phlebitis was observed in 17.4%. Bacteria isolated from colonised catheter tips were Staphylococcus aureus (60.5%), Staphylococcus epidermidis (23.5%). The most common organism isolated from the hub was Staphylococcus aureus (56.8%) followed by Staphylococcus epidermidis (18.1%). Gram positive and negative organisms were sensitive to ciprofloxacin, gentamycin for gramnegative organisms and augmentin, cefuroxime, ceftriaxone for the gram-positive organisms. After logistic regression, factors such oedema, modified Glasgow coma score of
- Published
- 2009
14. Role of microscopic examination of stool specimens in the diagnosis of campylobacter infection from children with acute diarrhoea in Kampala, Uganda
- Author
-
Mshana, S.E., Joloba, M.L., Kakooza, A., Kaddu-Mulindwa, D., Mshana, S.E., Joloba, M.L., Kakooza, A., and Kaddu-Mulindwa, D.
- Abstract
Campylobacter species are a frequent cause of enteritis and less often of extraintestinal infections in humans. The diagnosis of campylobacter infection depends mainly on culture which is difficult and expensive to be done as routine in most clinical microbiology laboratories in the developing countries. This study was conducted to determine the sensitivity and specificity of Gram-stain of the stool in diagnosis of campylobacter infection, using culture as the gold standard. A total of 226 stool specimens were obtained from children with acute diarrhoea, attending Mulago Hospital in Kampala, Uganda. Stool smears were made and conventional Gram stain done using 0.3% carbol-fuschin as counter stain for 5 minutes. Mucous part of the stool was cultured in Charcoal Ceferaperazone Deoxycholate Agar and blood contained selective media. A total of 21 stool samples (9.3%) were positive by culture and 17 (7.5%) by Gram stain. Sensitivity and specificity of Gram stain in the diagnosis of campylobacter infection was 76% and 99.5%, respectively with positive predictive value of 94.1%. A total of 127 (56.2%) had white blood cells (WBC) in stool and there was strong association between WBC in stool and the presence of campylobacter infection (P=0.001). Gram stain is a good alternative in diagnosis of campylobacter infection in place where facilities for culture are limited.
- Published
- 2011
15. Bacterial aetiology and outcome in children with severe pneumonia in Uganda
- Author
-
Nantanda, R, Hildenwall, H, Peterson, S, Kaddu-Mulindwa, D, Kalyesubula, I, Tumwine, K, Nantanda, R, Hildenwall, H, Peterson, S, Kaddu-Mulindwa, D, Kalyesubula, I, and Tumwine, K
- Abstract
Background: Pneumonia is a major cause of morbidity and mortality in the 'under-5s' and in Uganda accounts for 10-30% of childhood deaths. Antibiotic resistance is increasing. Objective: To describe the bacterial aetiology, antimicrobial sensitivity and outcome of severe pneumonia among children aged 2-59 months admitted to the Acute Care Unit, Mulago Hospital, Uganda. Methods: A total of 157 children aged 2-59 months with symptoms of severe pneumonia according to WHO guidelines were recruited over a 4-month period in 2005/2006. Blood and induced sputum were obtained for culture, and chest radiographs were undertaken. Children were clinically classified as having severe or very severe pneumonia and were followed up for a maximum of 7 days. Results: Bacteraemia was detected in 15.9% of patients with Staphylococcus aureus (36%) and Streptococcus pneumoniae (28%) were the organisms most commonly isolated. Bacteria were isolated from sputum in half of the children, the commonest organisms being Streptococcus pneumoniae (45.9%), Haemophilus influenzae (23.5%) and Klebsiella species (22.4%). Staphylococcus aureus had only 33.3% sensitivity to chloramphenicol and H. influenzae isolates were completely resistant. S. pneumoniae was sensitive to chloramphenicol in 87.4% of cases. The case fatality rate was 15.5%. Independent predictors of death were very severe pneumonia (OR 12.9, CI 2.5-65.8), hypoxaemia (SaO(2) <92%, OR 4.9, CI 1.2-19.5) and severe malnutrition (OR 16.5, CI 4.2-65.5). Conclusion: S. aureus, S. pneumoniae and H. influenzae are common bacterial causes of severe pneumonia. Chloramphenicol, the current first-line antibiotic for treating severe pneumonia in Ugandan children, is useful in pneumonia caused by S. pneumoniae but other common bacteria show resistance. The presence of severe malnutrition, hypoxaemia and very severe pneumonia increase the risk of death and should be considered in case management protocols.
- Published
- 2008
- Full Text
- View/download PDF
16. Faecal Calprotectin in HIV-infected, HAART-naïve Ugandan Children
- Author
-
Hestvik, E., primary, Olafsdottir, E., additional, Tylleskar, T., additional, Aksnes, L., additional, Kaddu-Mulindwa, D., additional, Ndeezi, G., additional, Tumwine, J.K., additional, and Grahnquist, L., additional
- Published
- 2012
- Full Text
- View/download PDF
17. Role of microscopic examination of stool specimens in the diagnosis of campylobacter infection from children with acute diarrhoea in Kampala, Uganda
- Author
-
Mshana, S. E., primary, Joloba, M. L., additional, Kakooza, A., additional, and Kaddu-Mulindwa, D., additional
- Published
- 2010
- Full Text
- View/download PDF
18. Bacterial aetiology and outcome in children with severe pneumonia in Uganda
- Author
-
Nantanda, R., primary, Hildenwall, H., additional, Peterson, S., additional, Kaddu-Mulindwa, D., additional, Kalyesubula, I., additional, and K.Tumwine, J., additional
- Published
- 2008
- Full Text
- View/download PDF
19. Occurrence of Shiga toxin-producing Escherichia coli in fecal samples from children with diarrhea and from healthy zebu cattle in Uganda
- Author
-
Kaddu-Mulindwa, D, primary
- Published
- 2001
- Full Text
- View/download PDF
20. Relative prevalence of methicilline resistant Staphylococcus aureus and its susceptibility pattern in Mulago Hospital, Kampala, Uganda.
- Author
-
OJULONG, J., MWAMBU, T. P., JOLOBA, M., BWANGA, F., and KADDU-MULINDWA, D. H.
- Abstract
Methicilline resistant Staphylococcus aureus (MRSA) strains are becoming increasingly multiresistant, and have recently developed resistance to vancomycin, which has been used successfully to treat MRSA for many years. In-vitro determination of resistance patterns of S. aureus is critical in terms of administering suitable antimicrobial treatments. The objective of this study was to determine the relative prevalence of MRSA among S. aureus isolates from surgical site infections and their antibiotic susceptibility pattern in Mulago Hospital, Kampala, Uganda. One hundred eighty eight pus swabs were collected from patients with surgical site infections. Swabs were inoculated for culture at the Microbiology Laboratory of the Faculty of Medicine, Makerere University. S. aurues isolates were identified using standard procedures and tested for oxacillin resistance according to methods of the National Committee for Clinical Laboratory Standards. Out of the 188 specimens, 54 (28.7%) grew S. aureus. Seventeen (31.5%) of the S. aureus isolates were confirmed as MRSA by PCR. Resistance rates of MRSA were 88.2% for trimethoprim-sulfamethoxazole, 88.2% for erythromycin, 58.8% for gentamycin, 70.6% for ciprofloxacin, and 88.2% for chloramphenicol. All isolates were found to be sensitive to vancomycin and clindamycin though the D-test was found to be positive in 82.4% of the isolates. In our region, although methicillin resistance increased in S. aureus strains, because of the unavailability and the high cost of alternative antibiotics, gentamycin is still suggested as an alternative for treatment of S. aureus infections. These results however indicate that vancomycin seemed to be the only antimicrobial agent effective against MRSA and it could be the drug of choice in treating multidrug resistant MRSA infection. [ABSTRACT FROM AUTHOR]
- Published
- 2009
- Full Text
- View/download PDF
21. Rolle der FDG-PET/CT zur Erkennung eines Befalls des Knochenmarkes (KM) beim initialen Staging des aggressiven Non-Hodgkin-Lymphoms (NHL).
- Author
-
Grosse, J, Altmann, B, Kaddu-Mulindwa, D, Held, G, Ziepert, M, Menhart, K, Angel, S, Stilgenbauer, S, Pfreundschuh, M, Pöschel, V, and Hellwig, D
- Published
- 2020
- Full Text
- View/download PDF
22. PB2104: DOSE-DENSE CHEMOTHERAPY WITH R-CHOP-14 IN OLDER ADULTS AGED ≥80 YEARS WITH DIFFUSE LARGE B-CELL LYMPHOMA
- Author
-
Konstantinos Christofyllakis, Dilbaz Z, Denker S, Ankermann C, Kunte A, Poeschel V, Bewarder M, Kaddu-Mulindwa D, Stilgenbauer S, Thurner L, Na I, and Bittenbring J
- Subjects
Hematology
23. Bacteriuria among adult non-pregnant women attending Mulago hospital assessment centre in Uganda
- Author
-
Mwaka, A. D., Harriet Mayanja-Kizza, Kigonya, E., and Kaddu-Mulindwa, D.
- Subjects
Adult ,Adolescent ,Bacteria ,Bacteriuria ,Original Articles ,Bacterial Infections ,Microbial Sensitivity Tests ,Middle Aged ,Anti-Bacterial Agents ,Young Adult ,Age Distribution ,Cross-Sectional Studies ,Prevalence ,Humans ,Female ,Uganda ,Hospitals, Teaching ,Bacteriuria, empiric therapy, E. coli, Uganda, urinary tract infections ,Aged - Abstract
Background: Urinary tract infections (UTIs) in women are a common problem in primary health care settings. Resistance of bacterial uropathogens to commonly used antibiotics is common in many places.Objectives: To determine the prevalence of UTI, associated uropathogens and their antimicrobial susceptibility.Methods: A cross section study carried out at Mulago hospital outpatients’ department. Midstream urine samples (MSU) were collected from 399 women, who gave informed consent and fulfilled other study criteria. Quantitative culture method, identification of uropathogens and antibiotic susceptibility testing using the Kirby-Bauer disc diffusion technique wereapplied to the isolates.Results: Out of 399 MSU samples, 40 pure significant bacterial growths (>105 colony forming units (cfu)/ml of urine) were isolated and these included Escherichia coli, 23 (57.5%), Staphylococcus aureus, 9 (22.5%), Enterococci spp, 6 (15%) and Klebsiella pneumoniae, 2 (5.0%). Overall, sensitivities were: nitrofurantoin (98.3%), cefuroxime (89.3%), andcotrimoxazole (20%) by all uropathogens isolated.Conclusions: Culture positive UTI among adult non-pregnant women are a common problem, occurring in 10% of the study population. Most bacterial uropathogens showed high sensitivity to nitrofurantoin but low sensitivity to SXT. Recommendations: Nitrofurantoin should be considered as drug of choice for empirical treatment of community acquired uncomplicated UTI in adult non-pregnant women.
24. Survival of Some Pathogenic and Facultative Pathogenic Bacteria in Groundwater
- Author
-
Filip, Z., primary, Kaddu-Mulindwa, D., primary, and Milde, G., primary
- Published
- 1988
- Full Text
- View/download PDF
25. Survival and Adhesion of some Pathogenic and Facultative Pathogenic Micro-Organisms in Groundwater
- Author
-
Filip, Z., primary, Kaddu-Mulindwa, D., primary, and Milde, G., primary
- Published
- 1987
- Full Text
- View/download PDF
26. Nasopharyngeal carriage rate of Streptococcus pneumoniae in Ugandan children with sickle cell disease
- Author
-
Kateete David P, Kajumbula Henry, Kaddu-Mulindwa Deogratias H, and Ssevviri Augustine K
- Subjects
Medicine ,Biology (General) ,QH301-705.5 ,Science (General) ,Q1-390 - Abstract
Abstract Background Nasopharyngeal carriage of Streptococcus pneumoniae is a determinant for invasive pneumococcal disease, which often complicates homozygous sickle cell disease. Here, we determined the nasopharyngeal carriage rate of S. pneumoniae in Ugandan children with homozygous sickle cell disease, who attended the outpatient Sickle Cell Clinic at Mulago National Referral hospital in Kampala, Uganda. Results S. pneumoniae occurred in 27 of the 81 children with homozygous sickle cell disease (giving a carriage rate of 33%, 27/81). Twenty three children were previously hospitalized of whom S. pneumoniae occurred in only two (9%, 2/23), while among the 58 who were not previously hospitalized it occurred in 25 (43%, 25/58, χ2 = 8.8, p = 0.003), meaning there is an association between high carriage rate and no hospitalization. Two children previously immunized with the pneumococcal conjugate vaccine did not carry the organism. Prior antimicrobial usage was reported in 53 children (65%, 53/81). There was high resistance of pneumococci to penicillin (100%, 27/27) and trimethoprime-sulfamethoxazole (97%, 26/27), but low resistance to other antimicrobials. Of the 70 children without sickle cell disease, S. pneumoniae occurred in 38 (54%, 38/70) of whom 43 were males and 27 females (53% males, 23/43, and 56% females, 15/27). Conclusion Nasopharyngeal carriage of penicillin resistant pneumococci in Ugandan children with homozygous sickle cell disease is high. While nasopharyngeal carriage of S. pneumoniae is a determinant for invasive pneumococcal disease, pneumococcal bacteremia is reportedly low in Ugandan children with sickle cell disease. Studies on the contribution of high carriage rates to invasive pneumococcal disease in these children will be helpful. This is the first report on pneumococcal carriage rate in Ugandan children with sickle cell disease.
- Published
- 2012
- Full Text
- View/download PDF
27. Faecal calprotectin concentrations in apparently healthy children aged 0-12 years in urban Kampala, Uganda: a community-based survey
- Author
-
Grahnquist Lena, Ndeezi Grace, Tylleskar Thorkild, Tumwine James K, Hestvik Elin, Kaddu-Mulindwa Deogratias H, Aksnes Lage, and Olafsdottir Edda
- Subjects
Pediatrics ,RJ1-570 - Abstract
Abstract Background Calprotectin is a calcium and zinc binding protein, abundant in neutrophils and is extremely stable in faeces. Faecal calprotectin is used as a non-specific marker for gastrointestinal inflammation. It has a good diagnostic precision to distinguish between irritable bowel syndrome and inflammatory bowel disease. Studies have established normal concentrations in healthy children; all these studies have been performed in high-income countries. The objective of this study was to determine the concentration of faecal calprotectin in apparently healthy children aged 0-12 years in urban Kampala, Uganda. Method We tested 302 apparently healthy children aged, age 0-12 years (162 female, 140 male) in urban Kampala, Uganda. The children were recruited consecutively by door-to-door visits. Faecal calprotectin was analyzed using a quantitative enzyme-linked immunosorbent assay. Faeces were also tested for Helicobacter pylori (H. pylori) antigen, for growth of enteropathogens and microscopy was performed to assess protozoa and helminths. A short standardized interview with socio-demographic information and medical history was obtained to assess health status of the children. Results In the different age groups the median faecal calprotectin concentrations were 249 mg/kg in 0 < 1 year (n = 54), 75 mg/kg in 1 < 4 years (n = 89) and 28 mg/kg in 4 < 12 years (n = 159). There was no significant difference in faecal calprotectin concentrations and education of female caretaker, wealth index, gender, habits of using mosquito nets, being colonized with H. pylori or having other pathogens in the stool. Conclusion Concentrations of faecal calprotectin among healthy children, living in urban Ugandan, a low-income country, are comparable to those in healthy children living in high-income countries. In children older than 4 years, the faecal calprotectin concentration is low. In healthy infants faecal calprotectin is high. The suggested cut-off concentrations in the literature can be used in apparently healthy Ugandan children. This finding also shows that healthy children living under poor circumstances do not have a constant inflammation in the gut. We see an opportunity to use this relatively inexpensive test for further understanding and investigations of gut inflammation in children living in low-income countries.
- Published
- 2011
- Full Text
- View/download PDF
28. Helicobacter pylori in apparently healthy children aged 0-12 years in urban Kampala, Uganda: a community-based cross sectional survey
- Author
-
Ndeezi Grace, Kaddu-Mulindwa Deogratias H, Tylleskar Thorkild, Hestvik Elin, Grahnquist Lena, Olafsdottir Edda, and Tumwine James K
- Subjects
Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Abstract Background Helicobacter pylori is one of the most common causes of bacterial infection in human beings. Studies have showed a high prevalence of Helicobacter pylori among people in low-income countries and colonization early in life. A monoclonal antigen test, performed on faeces, HpSA®ImmunoCardSTAT, has a high sensitivity, specificity and accuracy and the faecal test can be performed in all ages, also in resource-limited settings. The main objective of this study was to determine the prevalence and factors associated with Helicobacter pylori colonization in apparently healthy children aged 0-12 years in urban Kampala, Uganda. Method We tested 427 apparently healthy children, age 0-12 years (211 males, 216 females), in a cross sectional survey for Helicobacter pylori colonization using HpSA ®ImmunoCardSTAT. A short standardized interview with socio-demographic information and medical history was used to assess risk factors. Results The overall prevalence of Helicobacter pylori in the 427 children was 44.3% (189 out of 427). Early colonization was common, 28.7%, in children younger than 1 year of age. The age specific rates were 46.0% in children age 1- < 3 years, 51.7% in children age 3- < 6 years, 54.8% in children age 6- < 9 years and 40.0% in children age 9- < 12 years. There was a significant difference in prevalence by gender; female 38.5% versus male 49.8% and by type of housing; permanent house 38.5% versus semi-permanent house 48.6%. Congestive living and education level of the female caretaker showed a clear trend for a difference in prevalence. Factors independently associated with Helicobacter pylori colonization included: drugs taken last three months, using a pit latrine, sources of drinking water and wealth index. Conclusion The prevalence of Helicobacter pylori colonization among urban Ugandan children is high at an early age and increases with age. The impact of Helicobacter pylori colonization on children's health in Uganda needs to be further clarified.
- Published
- 2010
- Full Text
- View/download PDF
29. Bacteraemia among severely malnourished children infected and uninfected with the human immunodeficiency virus-1 in Kampala, Uganda
- Author
-
Kaddu-Mulindwa Deogratias H, Tylleskär Thorkild, Bachou Hanifa, and Tumwine James K
- Subjects
Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background To establish the magnitude of bacteraemia in severely malnourished children, and describe the types of bacteria and antimicrobial sensitivity by HIV status. Method Isolates were recovered from 76 blood specimens. Antibiotic susceptibility tests were performed using commercial antibiotic disks and demographic and clinical findings were recorded. Results Of the 450 children 63% were male; median age 17.0 months (inter quartile range, IQR 12–24) and 57% had oedema. 151 (36.7 %) of 411 tested HIV-positive; 76 (17.1%) of 445 blood specimens grew bacterial isolates; 58% were Gram negative – S. typhimurium (27.6%) and S. enteriditis (11.8%). Staph. aureus (26.3%) and Strep. pneumoniae (13.2%) were the main Gram positive organisms. There was no difference in the risk of bacteraemia by HIV status, age < 24 months, male sex, or oedema, except for oral thrush (OR 2.3 CI 1.0–5.1) and hypoalbuminaemia (OR 3.5 CI 1.0–12.1). Isolates from severely immuno-suppressed children (CD4% Salmonella enteriditis (OR 5.4; CI 1.6 – 17.4). The isolates were susceptible (≥ 80%) to ciprofloxacin, ceftriaxone and gentamicin; with low susceptibility to chlorampenicol, ampicillin (< 50%) and co-trimoxazole ( Conclusion Bacteraemia affects 1 in every 6 severely malnourished children and carries high mortality especially among the HIV-positive. Given the high level of resistance to common antibiotics, there is need for clinical trials to determine the best combinations of antibiotics for management of bacteraemia in severely malnourished children.
- Published
- 2006
- Full Text
- View/download PDF
30. Survival of some pathogenic and facultative pathogenic bacteria in groundwater
- Author
-
Milde, G., Filip, Z., and Kaddu-Mulindwa, D.
- Subjects
BACTERIAL pollution of water ,BACTERIA ,GROUNDWATER - Published
- 1988
31. An inherited genetic variant of the CEP72 gene is associated with the development of vincristine-induced peripheral neuropathy in female patients with aggressive B-cell lymphoma.
- Author
-
Christofyllakis K, Kaddu-Mulindwa D, Lesan V, Rixecker T, Kos IA, Held G, Regitz E, Pfreundschuh M, Bittenbring JT, Thurner L, Poeschel V, Ziepert M, Altmann B, and Bewarder M
- Abstract
Vincristine-induced peripheral neuropathy (VIPN) is an adverse effect of regimens used for the treatment of aggressive B-cell non-Hodgkin lymphoma (B-NHL). A single-nucleotide polymorphism (SNP) in the promotor region of the CEP72 gene has been identified as risk factor for the development of VIPN in children. To validate these results in adults we aimed to determine the association of the high-risk CEP72 (rs924607 TT genotype) with the occurrence and severity of VIPN. Analysis of SNP rs924607 (TT, CC or CT) was performed in all enrolled patients with available blood samples with a TaqMan genotyping assay. Rates and grades of VIPN were assessed prospectively as part of the RICOVER-60 trial. CEP72 genotype could be assessed in 519 patients. VIPN data was available for 499/519 patients who were included in the final analysis. 286 (57%) patients developed VIPN of any grade during treatment. Grade 2-4 VIPN occurred in 33% (166/499) of patients. The high-risk CEP72 TT genotype at rs924607 was identified in 97/499 (19%) patients. The TT genotype was not correlated with VIPN in the overall study population compared to patients with either CC or CT genotypes (p = 0.748). However, in the subgroup of female patients, the TT genotype was associated with increased occurrence of any-grade VIPN as well as grade 2-4 VIPN as compared to patients with either CC or CT genotypes (p = 0.016 and p = 0.020, respectively). Thus, the SNP rs924607 in the CEP72 gene is associated with increased VIPN incidence in female patients with aggressive B-NHL treated with CHOP chemotherapy. Trial registration ClinicalTrials.gov identifier: NCT00052936, submission date: 2005-06-23, EudraCT Number: 2010-019587-36., (© 2024. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
32. Comparison of R-CHOP-14 and R-mini-CHOP in older adults with diffuse large B-cell lymphoma-A retrospective multicenter cohort study.
- Author
-
Dilbaz ZG, Denker S, Ankermann C, Bittenbring JT, Kaddu-Mulindwa D, Kunte AS, Hünecke S, Poeschel V, Stilgenbauer S, Thurner L, Na IK, Bewarder M, and Christofyllakis K
- Abstract
Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma entity, and its incidence increases with age. There is a paucity of data regarding use of biweekly R-CHOP (R-CHOP-14) in patients ≥80 years of age. We performed a retrospective cohort study of patients with DLBCL aged ≥80 years treated with R-CHOP-14 and R-miniCHOP in two academic tertiary centers in Germany between 01/01/2005 and 12/30/2019. Overall, 79 patients were included. Median age was 84 years (range 80-91). Despite higher CR rates with R-CHOP-14 (71.4% vs. 52.4%), no statistically significant difference could be found between patients treated with R-CHOP-14 and R-miniCHOP regarding overall survival (OS) (p = .88, HR 0.94, 95% CI = 0.47-1.90) and progression-free survival (PFS) (p = .26, HR 0.66, 95% CI = 0.32-1.36). At a median follow-up of 40 months, the 2-year OS rates were 56% with R-CHOP-14 and 53% with R-miniCHOP. Two-year PFS rates were 46% for R-CHOP-14 and 50% for R-mini-CHOP. Relative dose intensity of chemotherapy did not correlate with OS (p = .72). With the caveat of a retrospective cohort study, we conclude that lacking a difference in OS, R-miniCHOP should be preferred for most patients with untreated DLBCL aged ≥80 years., (© 2024 The Author(s). European Journal of Haematology published by John Wiley & Sons Ltd.)
- Published
- 2024
- Full Text
- View/download PDF
33. Hyper-N-glycosylated SEL1L3 as auto-antigenic B-cell receptor target of primary vitreoretinal lymphomas.
- Author
-
Elbert M, Neumann F, Kiefer M, Christofyllakis K, Balensiefer B, Kos I, Carbon G, Kaddu-Mulindwa D, Bittenbring JT, Fadle N, Regitz E, Fend F, Bonzheim I, Thurner L, and Bewarder M
- Subjects
- Humans, Glycosylation, Cell Line, Tumor, Retinal Neoplasms genetics, Retinal Neoplasms metabolism, Retinal Neoplasms pathology, Retinal Neoplasms immunology, Autoantigens immunology, Autoantigens metabolism, Lymphoma, Large B-Cell, Diffuse genetics, Lymphoma, Large B-Cell, Diffuse immunology, Lymphoma, Large B-Cell, Diffuse pathology, Lymphoma, Large B-Cell, Diffuse metabolism, Female, Male, Vitreous Body metabolism, Vitreous Body pathology, Middle Aged, Aged, Receptors, Antigen, B-Cell metabolism
- Abstract
Primary vitreoretinal lymphoma (PVRL) is a rare subtype of DLBCL and can progress into primary central nervous system lymphoma (PCNSL). To investigate the role of chronic antigenic stimulation in PVRL, we cloned and expressed B-cell receptors (BCR) from PVRL patients and tested for binding against human auto-antigens. SEL1L3, a protein with multiple glycosylation sites, was identified as the BCR target in 3/20 PVRL cases. SEL1L3 induces proliferation and BCR pathway activation in aggressive lymphoma cell lines. Moreover, SEL1L3 conjugated to a toxin killed exclusively lymphoma cells with respective BCR-reactivity. Western Blot analysis indicates the occurrence of hyper-N-glycosylation of SEL1L3 at aa 527 in PVRL patients with SEL1L3-reactive BCRs. The BCR of a PVRL patient with serum antibodies against SEL1L3 was cloned from a vitreous body biopsy at diagnosis and of a systemic manifestation at relapse. VH4-04*07 was used in both lymphoma manifestations with highly conserved CDR3 regions. Both BCRs showed binding to SEL1L3, suggesting continued dependence of lymphoma cells on antigen stimulation. These results indicate an important role of antigenic stimulation by post-translationally modified auto-antigens in the genesis of PVRL. They also provide the basis for a new treatment approach targeting unique lymphoma BCRs with ultimate specificity., (© 2024. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
34. PLWH treated with modern ART and high CD4 T cell counts: no evidence of HIV-associated vasculopathy measured by extra- and intracranial ultrasound.
- Author
-
Fousse M, Heit M, Fassbender K, and Kaddu-Mulindwa D
- Subjects
- Humans, Ultrasonography, Cell Count, CD4-Positive T-Lymphocytes, HIV Infections complications, HIV Infections diagnostic imaging, HIV Infections drug therapy
- Published
- 2024
- Full Text
- View/download PDF
35. A dynamic time-to-event model for prediction of acute graft-versus-host disease in patients after allogeneic hematopoietic stem cell transplantation.
- Author
-
Och K, Turki AT, Götz KM, Selzer D, Brossette C, Theobald S, Braun Y, Graf N, Rauch J, Rohm K, Weiler G, Kiefer S, Schwarz U, Eisenberg L, Pfeifer N, Ihle M, Grandjean A, Fix S, Riede C, Rissland J, Smola S, Beelen DW, Kaddu-Mulindwa D, Bittenbring J, and Lehr T
- Subjects
- Humans, Male, Female, Adult, Middle Aged, Risk Factors, Young Adult, Acute Disease, Time Factors, Adolescent, Aged, Cyclosporine therapeutic use, Graft vs Host Disease etiology, Hematopoietic Stem Cell Transplantation adverse effects, Transplantation, Homologous adverse effects, Transplantation Conditioning adverse effects, Transplantation Conditioning methods
- Abstract
Background: Acute graft-versus-host disease (aGvHD) is a major cause of death for patients following allogeneic hematopoietic stem cell transplantation (HSCT). Effective management of moderate to severe aGvHD remains challenging despite recent advances in HSCT, emphasizing the importance of prophylaxis and risk factor identification., Methods: In this study, we analyzed data from 1479 adults who underwent HSCT between 2005 and 2017 to investigate the effects of aGvHD prophylaxis and time-dependent risk factors on the development of grades II-IV aGvHD within 100 days post-HSCT., Results: Using a dynamic longitudinal time-to-event model, we observed a non-monotonic baseline hazard overtime with a low hazard during the first few days and a maximum hazard at day 17, described by Bateman function with a mean transit time of approximately 11 days. Multivariable analysis revealed significant time-dependent effects of white blood cell counts and cyclosporine A exposure as well as static effects of female donors for male recipients, patients with matched related donors, conditioning regimen consisting of fludarabine plus total body irradiation, and patient age in recipients of grafts from related donors on the risk to develop grades II-IV aGvHD. Additionally, we found that higher cumulative hazard on day 7 after allo-HSCT are associated with an increased incidence of grades II-IV aGvHD within 100 days indicating that an individual assessment of the cumulative hazard on day 7 could potentially serve as valuable predictor for later grades II-IV aGvHD development. Using the final model, stochastic simulations were performed to explore covariate effects on the cumulative incidence over time and to estimate risk ratios., Conclusion: Overall, the presented model showed good descriptive and predictive performance and provides valuable insights into the interplay of multiple static and time-dependent risk factors for the prediction of aGvHD., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)
- Published
- 2024
- Full Text
- View/download PDF
36. Impact of vincristine dose reduction on outcomes of patients with aggressive B-cell lymphoma treated with (R)-CHOP.
- Author
-
Bewarder M, Kaddu-Mulindwa D, Kos IA, Lesan V, Held G, Poeschel V, Thurner L, Bittenbring JT, Schmitz N, Truemper L, Pfreundschuh M, Christofyllakis K, Loeffler M, Altmann B, and Ziepert M
- Subjects
- Humans, Vincristine therapeutic use, Drug Tapering, Rituximab therapeutic use, Cyclophosphamide therapeutic use, Prednisone therapeutic use, Doxorubicin therapeutic use, Antineoplastic Combined Chemotherapy Protocols adverse effects, Lymphoma, B-Cell drug therapy, Lymphoma, Large B-Cell, Diffuse pathology
- Published
- 2023
- Full Text
- View/download PDF
37. Vitamin D Enhances Immune Effector Pathways of NK Cells Thus Providing a Mechanistic Explanation for the Increased Effectiveness of Therapeutic Monoclonal Antibodies.
- Author
-
Christofyllakis K, Neumann F, Bewarder M, Thurner L, Kaddu-Mulindwa D, Kos IA, Lesan V, and Bittenbring JT
- Subjects
- Humans, Female, Antibodies, Monoclonal, Vitamins, Killer Cells, Natural, Ubiquitins, Vitamin D, Vitamin D Deficiency
- Abstract
Patients with diffuse large cell lymphoma who have an adequate vitamin D supply derive significantly more benefit from immuno-chemotherapy with rituximab than patients with vitamin D deficiency; this is especially true for female patients. We have already been able to show that vitamin D increases the antibody-dependent cytotoxicity (ADCC) of NK cells in a sex-dependent manner, but it is unclear how vitamin D makes NK cells more efficient., Methods: Healthy individuals with vitamin D deficiency were supplemented with vitamin D to sufficient levels. NK cells were isolated from blood samples before and after vitamin D saturation. For transcriptome analysis, we used the Affymetrix Gene-Chip 2.0™. Gene expression analysis as well as supervised and unsupervised pathway analysis were performed., Results: Among others the "NK cell-associated cytotoxicity pathway" increased after vitamin D substitution. Five IFN-α subtypes (2, 4, 6, 7 and 10) and IFN-κ were more highly expressed and are mainly responsible in these pathways. In contrast, the pathway "interferon-gamma response", as well as other sets in cytokine production and chemotaxis showed a reduction. Toll-like receptor genes (TLR-8, TLR-7, TLR-2) were downregulated and, therefore, are responsible for the decline of these pathways. The same could be shown for the "ubiquitin-ligase" pathway., Conclusions: Increased expression of several IFN-α subtypes may explain the increased ADCC of NK cells in vitamin D-replenished and otherwise healthy subjects. Other regulators of interferon production and ADCC are compensatory upregulated in compensation, such as Toll-like receptors and those of the ubiquitin ligase, and normalize after vitamin D substitution.
- Published
- 2023
- Full Text
- View/download PDF
38. Radiation and Dose-densification of R-CHOP in Aggressive B-cell Lymphoma With Intermediate Prognosis: The UNFOLDER Study.
- Author
-
Thurner L, Ziepert M, Berdel C, Schmidt C, Borchmann P, Kaddu-Mulindwa D, Viardot A, Witzens-Harig M, Dierlamm J, Haenel M, Metzner B, Wulf G, Lengfelder E, Keller UB, Frickhofen N, Nickelsen M, Gaska T, Griesinger F, Mahlberg R, Marks R, Shpilberg O, Lindemann HW, Soekler M, Fischer von Weikersthal L, Kiehl M, Roemer E, Bentz M, Krammer-Steiner B, Trappe R, de Nully Brown P, Federico M, Merli F, Engelhard M, Glass B, Schmitz N, Truemper L, Bewarder M, Hartmann F, Murawski N, Stilgenbauer S, Rosenwald A, Altmann B, Schmidberger H, Fleckenstein J, Loeffler M, Poeschel V, and Held G
- Abstract
UNFOLDER (Unfavorable Young Low-Risk Densification of R-Chemo Regimens) is an international phase-3 trial in patients 18-60 years with aggressive B-cell lymphoma and intermediate prognosis defined by age-adjusted International Prognostic Index (aaIPI) of 0 and bulky disease (≥7.5 cm) or aaIPI of 1. In a 2 × 2 factorial design patients were randomized to 6× R-CHOP-14 or 6× R-CHOP-21 (rituximab, cyclophosphamide, doxorubicin, vincristine, and prediso[lo]ne) and to consolidation radiotherapy to extralymphatic and bulky disease or observation. Response was assessed according to the standardized response criteria published in 1999, not including F-18 fluordesoxyglucose positron emission tomography/computed tomography (FDG-PET). Primary endpoint was event-free survival (EFS). A total of 695 of 700 patients were eligible for the intention-to-treat analysis. Totally 467 patients qualified for radiotherapy of whom 305 patients were randomized to receive radiotherapy (R-CHOP-21: 155; R-CHOP-14: 150) and 162 to observation (R-CHOP-21: 81, R-CHOP-14: 81). Two hundred twenty-eight patients not qualifying for radiotherapy were randomized for R-CHOP-14 versus R-CHOP-21. After a median observation of 66 months 3-year EFS was superior in the radiotherapy-arm versus observation-arm (84% versus 68%; P = 0.0012), due to a lower rate of partial responses (PR) (2% versus 11%). PR often triggered additional treatment, mostly radiotherapy. No significant difference was observed in progression-free survival (PFS) (89% versus 81%; P = 0.22) and overall survival (OS) (93% versus 93%; P = 0.51). Comparing R-CHOP-14 and R-CHOP-21 EFS, PFS and OS were not different. Patients randomized to radiotherapy had a superior EFS, largely due to a lower PR rate requiring less additional treatment (NCT00278408, EUDRACT 2005-005218-19)., Competing Interests: L. Thurner has received travel grants from Abbvie, Janssen and EUSA-Pharm, and has indicated consultancy for Takeda, Astra-Zeneca, Merck, EUSA-pharm. DK-M has received personal fees from Novartis, Astra-Zeneca, Gilead Sciences, GlaxoSmithKline, Janssen-Cilag, and nonfinancial support from Gilead Sciences, Janssen-Cilag, Takeda, Novartis. AV has received honoraria from Roche, Amgen, Kite, Gilead, Novartis, Bristol-Myers Squibb and has indicated a membership of the advisory board of Roche, Amgen, Kite, Gilead, Novartis, Bristol-Myers Squibb. UBK has received honoraria and advisory fees from Roche, Janssen-Cilag, Takeda, Bristol-Myers Squibb, Gilead, Hexal, Pfizer, Astra- Zeneca, Pentixapharm, Amgen, Novartis, MSD and has received clinical study support for Celgene, Takeda, BMS, Roche, Astra-Zeneca, Novartis, MSD, Janssen-Cilag, Pfizer. MN has received travel grants from Roche, Celgene and MSD and personal fees from Roche, Celgene, MSD, Janssen, Amgen, Incyte and Abbvie. FG participates in advisory board of Roche, Boehringer Ingelheim, Abbvie, Merck, Takeda, MSD, Sanofi, Pfizer, Novartis, Amgen and Janssen. RT has received grants from Atara and Roche and travel support from Roche, Atara, Celgene, Janssen and Abbvie; he has indicated a membership of the advisory board of Atara and Abbvie and has indicated consultancy for s Atara. PdNB has indicated consultancy for Roche, Incyte and Novartis. FM has received travel grants from Roche, Takeda, Janssen and Gilead and has indicated consultancy and advisory role for Roche, Gilead, Janssen, MSD, Takeda and Novartis. SS has received grants from Abbvie, Astra-Zeneca, Celgene, Gilead, Roche, Janssen, Novartis, Morphosys and has indicated consultancy for for Abbvie, Astra-Zeneca, Celgene, Gilead, Roche, Janssen, Novartis, Morphosys; he has received drug/equipment supplied by entity from Abbvie, Astra-Zeneca, Celgene, Gilead, Roche, Janssen, Novartis, Morphosys. VP has received grants from Deutsche Krebshilfe (German Cancer Aid), Chugai, Abbvie, Amgen, Roche and Bristol Myers Squibb. GH has received grants from Roche and Bristol Myers Squibb and personal fees from Bristol Myers Squibb, Roche, Amgen, Spectrum and MSD. All the other authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Hematology Association.)
- Published
- 2023
- Full Text
- View/download PDF
39. Ars2-containing bispecific, Fab- and IgG1-format BAR-bodies to target DLBCL cells.
- Author
-
Kiefer M, Thurner L, Bock T, Cetin O, Kos I, Lesan V, Kaddu-Mulindwa D, Bittenbring JT, Fadle N, Regitz E, Hoth M, Neumann F, Preuss KD, Pfreundschuh M, Christofyllakis K, and Bewarder M
- Abstract
Despite recent advances in the therapy of diffuse large B-cell lymphoma, not otherwise specified (DLBCL), around 30% of patients develop refractory disease or relapse after first-line treatment. Recently, Ars2 was reported as the auto-antigenic target of the B-cell receptor (BCR) in approximately 25% of activated B-cell DLBCL cases. Ars2 could be used to specifically target B cells expressing Ars2-reactive BCRs. However, the optimal therapeutic format to integrate Ars2 into has yet to be determined. To mimic therapeutic antibody formats, Ars2-containing bispecific and IgG1-like constructs (BCR antigens for reverse [BAR]-bodies) were developed. Two bispecific BAR-bodies connecting single-chain antibodies against CD16 or CD3 to the BCR-binding epitope of Ars2 were constructed. Both constructs showed strong binding to U2932 cells and induced effector cell-dependent and selective cytotoxicity against U2932 cells of up to 44% at concentrations of 20 μg/ml. Additionally, IgG1-format Ars2 BAR-bodies were constructed by replacing the variable heavy- and light-chain regions of a full-length antibody with the Ars2 epitope. IgG1-format Ars2 BAR-bodies also bound selectively to U2932 and OCI-Ly3 cells and induced selective cytotoxicity of up to 60% at 10 μg/ml. In conclusion, Ars2-containing bispecific and IgG1-format BAR-bodies both are new therapeutic formats to target DLBCL cells., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 The Authors. eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.)
- Published
- 2022
- Full Text
- View/download PDF
40. Adaptive humoral immune response and cellular immune status in cancer patients and patients under immunosuppression vaccinated against SARS-CoV-2.
- Author
-
Kos IA, Kiefer M, Brill K, Cetin O, Bittenbring JT, Ahlgrimm M, Smola S, Lohse S, Christofyllakis K, Kaddu-Mulindwa D, Neumann F, Bewarder M, and Thurner L
- Subjects
- Humans, Immunity, Humoral, SARS-CoV-2, COVID-19 Vaccines, Lenalidomide, Tumor Necrosis Factor Inhibitors, Antibodies, Viral, Immunosuppression Therapy, COVID-19 prevention & control, Neoplasms therapy, Autoimmune Diseases
- Abstract
Background: Patients with cancer and autoimmune diseases are at higher risk of severe COVID-19. They may not develop protective immune responses following vaccination. We investigated patients' cellular and humoral immune response after two COVID-19 vaccine doses., Research Design and Methods: Subjects were stratified into subgroups according to therapy and grade of immunosuppression at time of vaccination., Results: Antibody titers were compared to healthy controls. 32/122 (26%) did not develop detectable antibody titers. Of these, 22 (66.6%) had active therapy. Patients showed significant lower antibody titers compared to controls (median 790 vs. 3923 AU/mL, p = 0.026). Patients with active therapy had significant lower antibody titers compared to those without (median 302 vs. 3952 U/L P < 0.001). B-cell count was lower in the group without antibody titers (median 29.97 vs. 152.8; p = 0.002). 100% of patients under anti-CD20 therapy had no detectable antibody titer, followed by anti-TNF (66%), BTK inhibitors (50%), ruxolitinib (35.5%), TKI (14.2%), and lenalidomide (12.5%). Anti-CD20 therapy, ruxolitinib, BTK inhibitors, and anti-CD38 therapy presented significant lower antibody titers compared to controls., Conclusions: Patients undergoing therapy for cancer or autoimmune diseases are at higher risk of insufficient humoral immune response following COVID-19 vaccination. Furthermore, alterations in the B-cell compartment correlate with lower antibody titers.
- Published
- 2022
- Full Text
- View/download PDF
41. Fewer neurocognitive deficits and less brain atrophy by third ventricle measurement in PLWH treated with modern ART: A prospective analysis.
- Author
-
Kaddu-Mulindwa D, Heit M, Wagenpfeil G, Bewarder M, Fassbender K, Behnke S, Yilmaz U, and Fousse M
- Abstract
Background: Despite antiretroviral therapy, cognitive dysfunction seems to remain a major issue for people living with human immunodeficiency virus (PLWH). Previous studies showed a correlation between the width of the third ventricle (WTV) and neurocognitive disorders in PLWH., Patients and Methods: We investigated prevalence and correlation of neuropsychological disorders using WTV as a brain atrophy marker examined by transcranial sonography and MRI in PLWH and healthy age- and gender-matched controls. We used Becks Depression Inventory (BDI) for depression screening, the questionnaires Fatigue Severity Scale (FSS) for fatigue and Short-Form-36 (SF36) for quality of life (QoL) evaluation and Consortium to establish a registry for Alzheimer's disease (CERAD-PLUS) as neuropsychological test battery., Results: 52 PLWH (47 males) and 28 non-infected controls (23 males) with a median age of 52 years (24-78 years) and 51 years (22-79) were analyzed. WTV correlated significantly with age ( p < 0.01) but showed no significantly difference in PLWH (median = 3.4 mm) compared to healthy controls (median = 2.8 mm) ( p = 0.085). PLWH had both significantly higher BDI-Scores ( p = 0.005) and FSS-Scores ( p = 0.012). Controls reported higher QoL (SF-36) with significant differences in most items. However, the overall cognitive performance (CERAD total score) showed no significant difference. The WTV of all subjects correlated with neurocognitive performance measured as CERAD total score ( p = 0.009) and trail making tests A ( p < 0.001) and B ( p = 0.018). There was no correlation between the scores of BDI, FSS, SF-36, and CERAD-PLUS items and WTV., Conclusion: WTV is considered as a predictor of cognitive deficits in neurodegenerative diseases. Nevertheless, we found no significant difference in WTV or overall cognitive performance between PLWH and controls. PLWH suffer more often from depression and fatigue and report reduced QoL when compared to healthy controls., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kaddu-Mulindwa, Heit, Wagenpfeil, Bewarder, Fassbender, Behnke, Yilmaz and Fousse.)
- Published
- 2022
- Full Text
- View/download PDF
42. Salvage High-dose Melphalan With Autologous Stem cell Transplantation as Bridge to Consolidation Therapy for Chemoresistant Aggressive B-cell Lymphoma.
- Author
-
Kaddu-Mulindwa D, Gödel P, Kutsch N, Heger JM, Scheid C, Borchmann P, Holtick U, Held G, Thurner L, Bewarder M, Rixecker T, and Bittenbring JT
- Subjects
- Antineoplastic Combined Chemotherapy Protocols adverse effects, Consolidation Chemotherapy, Humans, Melphalan therapeutic use, Neoplasm Recurrence, Local drug therapy, Retrospective Studies, Salvage Therapy methods, Stem Cell Transplantation, Transplantation, Autologous, Hematopoietic Stem Cell Transplantation methods, Lymphoma drug therapy, Lymphoma, B-Cell drug therapy
- Abstract
Background: Patients suffering from refractory aggressive B-cell lymphoma not responding to salvage chemotherapy have a dismal prognosis. CAR T-cells or allogeneic stem cell transplantation (SCT) are potentially curative approaches. However, obtaining a remission, and lowering tumor burden before consolidation seems crucial for long-term efficacy of both treatment modalities., Materials and Methods: In this retrospective analysis, we reviewed patients with chemoresistant aggressive B-cell lymphoma, defined as being refractory or progressive to at least second line salvage chemotherapy including the regimen immediately preceding autologous stem cell transplantation (ASCT), treated at 2 tertiary centers, who were eligible for intensive treatment using single agent high-dose (HD) melphalan to obtain a remission before consolidating therapy., Results: We identified 36 patients that received single agent HD melphalan and ASCT as remission induction followed by CAR T-cells or allogeneic stem cell transplantation (SCT). Thirteen of the evaluable patients (39.4%) achieved a partial remission and 9 patients (27.73%) a complete remission, resulting in an overall response rate (ORR) of 66.7%. High remission rates were seen across all subgroups including patients with primary refractory lymphoma (ORR 58.3%), uncontrolled disease and high tumor burden as indicated by increased LDH levels (ORR 66.7% for patients with elevated LDH above 2 times upper limit of norm). 22 patients proceeded to allogeneic SCT and 5 to CAR T-cell therapy. Treatment related mortality of ASCT was 5.5% (2 patients, both due to infections). Two-year overall survival of all patients was 15.8%, primarily due to a high non-relapse mortality (45.5%) of allogeneic SCT patients treated with myeloablative conditioning chemotherapy., Conclusion: Single agent HD melphalan produces high remission rates in patients with chemoresistant, uncontrolled aggressive B-cell lymphoma and provides a window of opportunity for consolidation therapy., Microabstract: Patient with refractory/relapsed aggressive B-cell lymphoma after salvage therapy are an unmet medical need because of their very poor prognosis. In our retrospective analysis of 36 patients we showed that single agent high-dose melphalan can achieve high response rates (ORR 66.7%) even in uncontrolled disease enabling consolidation therapy e.g. with allogeneic stem cell transplantation or CAR T-cell therapy., (Copyright © 2022. Published by Elsevier Inc.)
- Published
- 2022
- Full Text
- View/download PDF
43. Management of Extranodal Marginal Zone Lymphoma: Present and Upcoming Perspectives.
- Author
-
Kaddu-Mulindwa D, Thurner L, Christofyllakis K, Bewarder M, and Kos IA
- Abstract
Extranodal marginal zone lymphoma (EMZL) encompasses a subgroup of non-Hodgkin lymphomas that often present with localized involvement and may manifest in a diversity of organs and tissues. EMZL pathogenesis is in some cases linked to chronic inflammation/infection, which may impose additional diagnostic and clinical challenges. The most studied and established connection is the presence of Helicobacter pylori in gastric EMZL. Due to its heterogeneity of presentation and intricate pathological features, treatment can be complex, and staging systems are decisive for the choice of therapy. Nevertheless, there is no consensus regarding the most suitable staging system, and recommendations vary among different countries. As a rule of thumb, in limited stages, a local therapy with surgery or radiation is the preferred option, and it is potentially curative. Of note, eradicating the causal agent may be an important step of treatment, especially in gastric EMZL, in which Helicobacter pylori eradication remains the first-line therapy for the majority of patients. In patients with more advanced stages, watch-and-wait is a valuable option, especially amongst those without clear indications for systemic therapy, and it may be carried on for several years. If watch-and-wait is not an option, systemic therapy may be needed. Even though several agents have been tested as monotherapy or in combination in recent years, there is no consensus regarding the first-line therapy, and decisions can vary depending on individual factors, such as age, clinical performance and stage. This review aims to discuss the several aspects of EMZL, including genetic milieu, pathogenesis and staging systems, that may influence the choice of therapy. In addition, we present a summary of evidence of several systemic therapies, compare different recommendations worldwide and discuss future perspectives and novelties in its therapy.
- Published
- 2022
- Full Text
- View/download PDF
44. IgG seroprevalence of COVID-19 among people living with HIV or at high risk of HIV in south-west Germany: A seroprevalence study.
- Author
-
Kaddu-Mulindwa D, Keuser L, Lesan V, Rissland J, Smola S, Werdecker V, Stilgenbauer S, Christofyllakis K, Thurner L, Bewarder M, Lohr B, Lutz J, Lohse S, and Rieke A
- Subjects
- Antibodies, Viral, COVID-19 Testing, Cross-Sectional Studies, Female, Humans, Immunoglobulin G, Male, Middle Aged, Prospective Studies, SARS-CoV-2, Seroepidemiologic Studies, Surveys and Questionnaires, COVID-19 diagnosis, COVID-19 epidemiology, HIV Infections complications, HIV Infections epidemiology
- Abstract
Objectives: Seroprevalence studies of SARS-CoV-2 have shown that there is a high number of undiagnosed missing cases. Seroprevalence of SARS-CoV-2 in people living with HIV (PLWH) is lacking. Therefore, we conducted a prospective cross-sectional study to estimate the seroprevalence of SARS-CoV-2 among PLWH without known diagnosis of COVID-19 in the south-west of Germany., Methods: Serological testing for SARS-CoV-2 immunoglobulin G (IgG) antibodies based on two assays was performed in PLWH who visited the outpatient HIV centre of two hospitals from April to June 2020. Additionally, patients had to answer questionnaires about possible COVID-19-related symptoms and predefined risk factors. Moreover, we tested 50 non-HIV-infected patients receiving post- or pre-exposure (PEP/PrEP) HIV prophylaxis., Results: In all, 594 (488 male, 106 female) PLWH (median age 51 years) and 50 PEP/PrEP-users were included in the study. The estimated seroprevalence of the PLWH cohort was 1.85% (11/594), with 11 positive tested cases in the cohort. Among all patients, only five had COVID-19-related symptoms. One PCR-positive patient did not show any antibody response in repeatedly carried out tests. None of the patients was hospitalized due to COVID-19. Three PrEP users were tested positive. Three patients had been previously diagnosed with SARS-COV-2 infection before inclusion. The used questionnaire did not help to detect SARS-CoV-2 positive patients., Conclusions: Despite the limitation of being only a snapshot in time because of the ongoing pandemic, to our knowledge this is the largest study so far on seroprevalence of SARS-CoV-2 in PLWH in Germany. Our study suggests that the seroprevalence of SARS-CoV-2 in PLWH is comparable to those previously reported for parts of the general German population and that the questionnaire used here might not be the best tool to predict COVID-19 diagnosis., (© 2021 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)
- Published
- 2022
- Full Text
- View/download PDF
45. Liver stiffness as surrogate parameter in emergency assessment for inpatient health care utilization.
- Author
-
Kaddu-Mulindwa D, von Martial M, Thiel-Bodenstaff A, Lesan V, Ewen S, Mahfoud F, Lammert F, and Krawczyk M
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Humans, Liver diagnostic imaging, Liver pathology, Liver Cirrhosis pathology, Male, Middle Aged, Patient Acceptance of Health Care, Young Adult, Elasticity Imaging Techniques, Inpatients
- Abstract
Background: Transient elastography (TE) allows non-invasive quantification of liver stiffness (LSM) and steatosis (controlled attenuation parameter, CAP). Here we test the feasibility and utility of TE in the emergency department (ED) and investigate whether LSM predicts longer hospitalization and reimbursement for non-elective patients., Methods: LSM and CAP were determined in prospectively recruited consecutive adult patients admitted to the ED of a tertiary referral center. Patients were stratified according to the 9.1 kPa and 13.0 kPa LSM cut-offs. Elastography measurements were correlated with clinical and outcome parameters, including duration of hospital stay and hospitalization costs., Results: In 200 ED patients (133 men, age 18 - 97 years), median LSM was 5.5 kPa (2.4 - 69.1 kPa), and median CAP was 252 dB/m (100 - 400 dB/m). In total, 39 patients (19.5%) presented with LSM ≥ 9.1 kPa, and 24 patients (12.0%) presented with LSM ≥ 13.0 kPa. Heart failure (n = 19) was associated with higher LSM (p = 0.045). Patients with LSM ≥ 9.1 kPa were significantly (p < 0.01) more likely to require longer hospitalization than those with lower LSM. Patients with LSM ≥ 13.0 kPa generated significantly (p = 0.001) higher costs as compared to patients with low LSM., Conclusions: Transient elastography represents an easily accessible screening tool in ED that might help identify patients in need of increased health care resources., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2022
- Full Text
- View/download PDF
46. Significant reduced loss of bone mineral density after four vs. six cycles of R-CHOP: an analysis of the FLYER-trial.
- Author
-
Kaddu-Mulindwa D, Lesan V, Berdel C, Stilgenbauer S, Bewarder M, Thurner L, Witzens-Harig M, Viardot A, Soekler M, Keller U, Truemper L, Christofyllakis K, Fleser O, Bittenbring JT, Poeschel V, Held G, and Jagoda P
- Subjects
- Antineoplastic Combined Chemotherapy Protocols adverse effects, Cyclophosphamide therapeutic use, Doxorubicin therapeutic use, Humans, Prednisone adverse effects, Rituximab, Vincristine adverse effects, Bone Density, Lymphoma, Large B-Cell, Diffuse diagnosis, Lymphoma, Large B-Cell, Diffuse drug therapy, Lymphoma, Large B-Cell, Diffuse etiology
- Abstract
Patients with diffuse large B-cell lymphoma (DLBCL) treated with the R-CHOP regime receive a high cumulative dose of prednisone. We used computer tomography-ascertained Hounsfield units (HU) as a surrogate parameter for bone mineral density (BMD) in three different locations of the L3 vertebral body at baseline and post-treatment. HU were measured in 50 patients with DLBCL of the previously published FLYER-trial which compared four cycles of R-CHOP + 2 × rituximab infusion to six cycles of R-CHOP in young, favorable DLBCL patients. In total, median loss was 26.8 HU in all patients over time. The median HU loss was significantly lower in the four cycles arm (21.3 HU vs. 41.3 HU, p = 0.023). In conclusion, young patients with DLBCL receiving R-CHOP have significant HU/BMD loss under treatment with R-CHOP. Patients receiving four cycles of R-CHOP had less HU/BMD loss than patients receiving six cycles.
- Published
- 2022
- Full Text
- View/download PDF
47. KIR2DS1-HLA-C status as a predictive marker for benefit from rituximab: a post-hoc analysis of the RICOVER-60 and CLL8 trials.
- Author
-
Kaddu-Mulindwa D, Altmann B, Robrecht S, Ziepert M, Regitz E, Tausch E, Held G, Poeschel V, Lesan V, Bittenbring JT, Thurner L, Pfreundschuh M, Christofyllakis K, Truemper L, Loeffler M, Schmitz N, Hoth M, Hallek M, Fischer K, Stilgenbauer S, Bewarder M, and Rixecker TM
- Subjects
- Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Cyclophosphamide therapeutic use, Doxorubicin therapeutic use, Humans, Middle Aged, Prednisone, Prospective Studies, Vincristine, HLA-C Antigens genetics, Receptors, KIR genetics, Rituximab therapeutic use
- Abstract
Background: The addition of rituximab to chemotherapy has substantially improved outcomes for patients with B-cell malignancies. The mechanisms of action of rituximab include activation of natural killer cells. Killer-cell immunoglobulin-like receptors (KIRs) mediate natural killer cell function through interaction with HLA. We evaluated the clinical impact of KIR-HLA genotypes on rituximab-containing therapy., Methods: For this post-hoc analysis, we used data from the RICOVER-60 trial (NCT00052936) as the discovery cohort and the CLL8 trial (NCT00281918) as the validation cohort. RICOVER-60 included patients aged 61-80 years with aggressive B-cell lymphoma treated with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) with or without rituximab. CLL8 included patients aged 30-81 years with chronic lymphocytic leukaemia treated with chemotherapy (fludarabine and cyclophosphamide; FC) with or without rituximab. We evaluated the KIR and HLA-C status of 519 patients with available blood samples in the RICOVER-60 trial and the KIR2DS1 and HLA-C status of 549 patients with available blood samples in the CLL8 trial, and evaluated their associations with event-free survival (RICOVER-60), progression-free survival, and overall survival (RICOVER-60 and CLL8)., Findings: In the RICOVER-60 trial, 201 (39%) patients were positive for KIR2DS1, 79 (15%) were homozygous for HLA-C2, and 36 (7%) were positive for KIR2DS1 and homozygous for HLA-C2. In the CLL8 trial, 206 (38%) patients were positive for KIR2DS1, 75 (14%) were homozygous for HLA-C2, and 26 (5%) were positive for KIR2DS1 and homozygous for HLA-C2. In the RICOVER-60 trial, both KIR2DS1 and HLA-C status were identified as independent risk factors for survival. KIR2DS1 positivity, homozygosity for HLA-C2, and subsequent KIR2DS1-HLA-C status were associated with adverse clinical outcome in patients receiving rituximab-containing therapy (event-free survival for patients with KIR2DS1-HLA-C2/C2 vs all other patients, HR 2·6 [95% CI 1·4-4·7], p=0·0015; progression-free survival, 2·7 [1·5-5·1], p=0·0013; overall survival, 2·8 [1·5-5·4], p=0·0016) but not in patients receiving CHOP chemotherapy only (event-free survival, 0·9 [0·5-1·7], p=0·85; progression-free survival, 1·1 [0·6-2·0], p=0·81; overall survival, 1·2 [0·6-2·4], p=0·53). A significant interaction between KIR2DS1-HLA-C status and rituximab was observed (p=0·018 for event-free survival and p=0·034 for progression-free survival). In contrast to all other patients, those positive for KIR2DS1 and homozygous for HLA-C2 did not benefit from adding rituximab to CHOP chemotherapy (event-free survival, 1·9 [0·8-4·6], p=0·16; progression-free survival, 1·4 [0·6-3·4], p=0·48; overall survival, 1·6 [0·6-4·3], p=0·33). In the CLL8 trial, KIR2DS1-HLA-C status was confirmed as a predictive marker for benefit from rituximab therapy (p=0·024 for the interaction of KIR2DS1-HLA-C status and rituximab regarding progression-free survival). In contrast to all other patients, those positive for KIR2DS1 and homozygous for HLA-C2 did not benefit from adding rituximab to FC chemotherapy (progression-free survival, 2·1 [0·9-4·9], p=0·094; overall survival, 2·6 [0·5-12·7], p=0·21)., Interpretation: Assessment of KIR2DS1 and HLA-C genotype might identify patients who would not benefit from rituximab, thereby allowing alternative therapies to be given. Further validation of these findings in prospective clinical trials is needed., Funding: F Hoffman La Roche., Competing Interests: Declaration of interests DK-M reports personal fees, grants, and non-financial support from Novartis, ViiV Healthcare, and Gilead. SS reports personal fees, grants, and non-financial support from AbbVie, Amgen, AstraZeneca, BeiGene, Bristol Myers Squibb, Celgene, Gilead, GlaxoSmithKline, Roche, Janssen, Novartis, and Sunesis. KF reports personal fees from AbbVie and Roche, outside the submitted work. VP reports non-financial support from Abbvie, Amgen, Bristol Myers Squibb, and Roche. JTB reports personal fees from Merck Sharp & Dohme and Incyte Pharmaceutical, and non-financial support from Gilead. LTh reports grants from the non-profit Wilhelm Sander Foundation, personal fees from EUSA Pharma and AstraZeneca, and non-financial support from AbbVie, EUSA Pharma, and Janssen. MB reports grants from the non-profit Deutsche José-Carreras Leukaemie Stiftung. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)
- Published
- 2022
- Full Text
- View/download PDF
48. Cost-effectiveness of precision cancer medicine-current challenges in the use of next generation sequencing for comprehensive tumour genomic profiling and the role of clinical utility frameworks (Review).
- Author
-
Christofyllakis K, Bittenbring JT, Thurner L, Ahlgrimm M, Stilgenbauer S, Bewarder M, and Kaddu-Mulindwa D
- Abstract
Precision cancer medicine (PCM) is an emerging paradigm in oncology, which includes tumour comprehensive genomic profiling (CGP) to enable molecularly guided therapy. However, cost-effectiveness analyses of PCM are faced with several challenges and, thus, its cost-effectiveness remains unclear. Early trials using only molecularly guided therapy were faced with the challenge of providing adequate measures of outcome, which probably explains the modest treatment benefits demonstrated. Endpoints like the progression-free survival (PFS)2/PFS1 ratio may assist in overcoming this issue. Moreover, specific tumour subtypes appear to benefit more from PCM. Costs associated with next-generation sequencing (NGS) for CGP are decreasing, but targeted therapy itself represents a major cost driver. CGP not only enables prediction of response to treatment, but also resistance, and could thus prevent administration of unnecessary (and costly) therapies. In clinical practice, the presence of clinical frameworks, such as the Recommendations for the Use of NGS for Patients with Metastatic Cancers from the ESMO Precision Medicine Working Group, and the ESMO Scale for Clinical Actionability of Molecular Targets, are essential in appropriately identifying situations where PCM is clinically meaningful, thereby improving its cost-effectiveness., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2020, Spandidos Publications.)
- Published
- 2022
- Full Text
- View/download PDF
49. Advances in Lymphoma Molecular Diagnostics.
- Author
-
Kos IA, Thurner L, Bittenbring JT, Christofyllakis K, and Kaddu-Mulindwa D
- Abstract
Lymphomas encompass a diverse group of malignant lymphoid neoplasms. Over recent years much scientific effort has been undertaken to identify and understand molecular changes in lymphomas, resulting in a wide range of genetic alterations that have been reported across all types of lymphomas. As many of these changes are now incorporated into the World Health Organization's defined criteria for the diagnostic evaluation of patients with lymphoid neoplasms, their accurate identification is crucial. Even if many alterations are not routinely evaluated in daily clinical practice, they may still have implications in risk stratification, treatment, prognosis or disease monitoring. Moreover, some alterations can be used for targeted treatment. Therefore, these advances in lymphoma molecular diagnostics in some cases have led to changes in treatment algorithms. Here, we give an overview of and discuss advances in molecular techniques in current clinical practice, as well as highlight some of them in a clinical context.
- Published
- 2021
- Full Text
- View/download PDF
50. FDG PET/CT to detect bone marrow involvement in the initial staging of patients with aggressive non-Hodgkin lymphoma: results from the prospective, multicenter PETAL and OPTIMAL>60 trials.
- Author
-
Kaddu-Mulindwa D, Altmann B, Held G, Angel S, Stilgenbauer S, Thurner L, Bewarder M, Schwier M, Pfreundschuh M, Löffler M, Menhart K, Grosse J, Ziepert M, Herrmann K, Dührsen U, Hüttmann A, Barbato F, Poeschel V, and Hellwig D
- Subjects
- Biopsy, Bone Marrow diagnostic imaging, Bone Marrow pathology, Humans, Neoplasm Staging, Positron Emission Tomography Computed Tomography, Positron-Emission Tomography, Prospective Studies, Retrospective Studies, Fluorodeoxyglucose F18, Lymphoma, Non-Hodgkin diagnostic imaging
- Abstract
Purpose: Fluorine-18 fluorodeoxyglucose positron emission tomography combined with computed tomography (FDG PET/CT) is the standard for staging aggressive non-Hodgkin lymphoma (NHL). Limited data from prospective studies is available to determine whether initial staging by FDG PET/CT provides treatment-relevant information of bone marrow (BM) involvement (BMI) and thus could spare BM biopsy (BMB)., Methods: Patients from PETAL (NCT00554164) and OPTIMAL>60 (NCT01478542) with aggressive B-cell NHL initially staged by FDG PET/CT and BMB were included in this pooled analysis. The reference standard to confirm BMI included a positive BMB and/or FDG PET/CT confirmed by targeted biopsy, complementary imaging (CT or magnetic resonance imaging), or concurrent disappearance of focal FDG-avid BM lesions with other lymphoma manifestations during immunochemotherapy., Results: Among 930 patients, BMI was detected by BMB in 85 (prevalence 9%) and by FDG PET/CT in 185 (20%) cases, for a total of 221 cases (24%). All 185 PET-positive cases were true positive, and 709 of 745 PET-negative cases were true negative. For BMB and FDG PET/CT, sensitivity was 38% (95% confidence interval [CI]: 32-45%) and 84% (CI: 78-88%), specificity 100% (CI: 99-100%) and 100% (CI: 99-100%), positive predictive value 100% (CI: 96-100%) and 100% (CI: 98-100%), and negative predictive value 84% (CI: 81-86%) and 95% (CI: 93-97%), respectively. In all of the 36 PET-negative cases with confirmed BMI patients had other adverse factors according to IPI that precluded a change of standard treatment. Thus, the BMB would not have influenced the patient management., Conclusion: In patients with aggressive B-cell NHL, routine BMB provides no critical staging information compared to FDG PET/CT and could therefore be omitted., Trial Registration: NCT00554164 and NCT01478542., (© 2021. The Author(s).)
- Published
- 2021
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.