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1.
Curr Pharm Teach Learn ; 15(8): 761-768, 2023 08.
Article de Anglais | MEDLINE | ID: mdl-37500304

RÉSUMÉ

BACKGROUND AND PURPOSE: Flip the Pharmacy (FtP) helps community pharmacies "flip" from dispensing- to patient-centered care models with assistance from practice transformation coaches ("coaches"). Purdue University College of Pharmacy created a novel advanced pharmacy practice experience (APPE) positioning students to serve as FtP coaches with oversight from four faculty coaches. This communication describes the APPE's design, characterizes preliminary student coaching outcomes, and identifies the APPE's strengths and limitations. EDUCATIONAL ACTIVITY AND SETTING: Twelve pharmacies were coached by APPE students. The APPE was designed to enhance student knowledge and skills in the scaled implementation of advanced patient care services through structured weekly activities: Week 1, student orientation and training; Week 2, preparing for pharmacy visits; and Weeks 3 and 4, conducting pharmacy visits. Students also performed recurring tasks each week, including managing social media accounts. FINDINGS: Twenty-eight students completed the APPE. Students conducted 81 in-person and 105 virtual visits. Faculty coaches were estimated to need 40 to 50  hours each month for coaching-related activities; involving student coaches reduced faculty coach time by approximately 50%, with faculty spending 20  hours on average per month vs. students spending 50.84  hours. APPE strengths included intentional weekly structuring and oversight and careful student transitions; limitations included minimal pharmacy vendor knowledge and limited rapport-building with pharmacies. SUMMARY: Early experiences demonstrated several benefits, including optimized faculty coach time and student exposure to practice transformation. Future endeavors to implement similar APPEs should incorporate strategies to enhance pharmacy vendor knowledge and strengthen relationship-building with participating pharmacies.


Sujet(s)
Enseignement pharmacie , Services pharmaceutiques , Pharmacies , Pharmacie , Étudiant pharmacie , Humains , Programme d'études
3.
Cancer Causes Control ; 32(7): 725-737, 2021 Jul.
Article de Anglais | MEDLINE | ID: mdl-33881651

RÉSUMÉ

PURPOSE: The aim of the World Health Organization-International Paediatric Oncology Society is to improve childhood cancer survival in low- and middle-income countries to 60% by 2030. This can be achieved using standardised evidence-based national treatment protocols for common childhood cancers. The aim of the study was to describe the development and implementation of the SACCSG NB-2017 neuroblastoma (NB) treatment protocol as part of the treatment harmonisation process of the South African Children's Cancer Study Group. METHODS: The Consolidated Framework for Implementation Research was used to identify factors that could influence the implementation of the national NB protocol as a health care intervention. The evaluation was done according to five interactive domains for implementation: intervention characteristics, inner setting, outer setting, individual or team characteristics and the implementation process. RESULTS: The protocol was developed over 26 months by 26 physicians involved in childhood cancer management. The process included an organisational phase, a resource identification phase, a development phase and a research ethics approval phase. Challenges included nationalised inertia, variable research ethical approval procedures with delays and uncoordinated clinical trial implementation. CONCLUSION: The implementation of the national NB protocol demonstrated the complexity of the implementation of a national childhood cancer treatment protocol. However, standardised paediatric cancer treatment protocols based on local expertise and resources in limited settings are feasible.


Sujet(s)
Prestations des soins de santé/organisation et administration , Programmes nationaux de santé/organisation et administration , Neuroblastome/thérapie , Protocoles antinéoplasiques , Enfant , Enfant d'âge préscolaire , Femelle , Humains , Nourrisson , Mâle , Évaluation des résultats des patients , République d'Afrique du Sud
4.
Pediatr Blood Cancer ; 68(4): e28878, 2021 04.
Article de Anglais | MEDLINE | ID: mdl-33484106

RÉSUMÉ

PURPOSE: Low- and middle-income countries (LMICs) reported a higher median age at diagnosis of neuroblastoma (NB) compared to high-income countries. The aim was to determine if the optimal age at diagnosis, which maximizes the difference in overall survival between younger versus older patients in the South African population was similar to the internationally validated 18 months age cut-point. METHODS: Four hundred sixty NB patients diagnosed between 2000 and 2016 were included. Receiver operating characteristic (ROC) curves were used to predict potential age cut-point values for overall survival in all risk group classifications. Risk ratios, sensitivity, specificity, and positive and negative predictive values at the specific cut-points were estimated with 95% confidence intervals, and time to mortality by age at the specific cut-points was shown with Kaplan-Meier curves and compared using log-rank tests. RESULTS: The median age at diagnosis for the total cohort was 31.9 months (range 0.2-204.7). For high-risk (HR), intermediate-risk, low-risk, and very low-risk patients, the median age at diagnosis was, respectively, 36 months (range 0.4-204.7), 16.8 months (range 0.7-145.1), 14.2 months (range 2.0-143.5), and 8.7 months (range 0.2-75.6). The ROC curves for the total NB cohort (area under the curve [AUC] 0.696; P < .001) and HR (AUC 0.682; P < .001) were analyzed further. The optimal cut-point value for the total cohort was at 19.1 months (sensitivity 59%; specificity 78%). The HR cohort had potential cut-point values identified at 18.4 months age at diagnosis (sensitivity 45%; specificity 87%) and 31.1 months (sensitivity 67%; specificity 62%). The 19.1 months cut-point value in the total cohort and the 18.4 months cut-point value in HR were as useful in predicting overall survival as 18 months age at diagnosis. CONCLUSION: The 18 months cut-point value appears to be the appropriate age for prognostic determination, despite the higher median age at diagnosis in South Africa.


Sujet(s)
Neuroblastome/diagnostic , Facteurs âges , Enfant , Enfant d'âge préscolaire , Études de cohortes , Femelle , Humains , Nourrisson , Mâle , Neuroblastome/épidémiologie , Pronostic , République d'Afrique du Sud , Analyse de survie
5.
Pediatr Surg Int ; 36(4): 457-469, 2020 Apr.
Article de Anglais | MEDLINE | ID: mdl-32112128

RÉSUMÉ

PURPOSE: To investigate the impact of local therapies on high-risk neuroblastoma (HR-NB) outcomes in South Africa. METHODS: Data from 295 patients with HR-NB from nine pediatric oncology units between 2000 and 2014 were analysed. All patients received chemotherapy. Five-year overall (OS) and event free survival (EFS) were determined for patients who had received local therapy, either surgery or radiotherapy or both. RESULTS: Surgery was performed in only 35.9% (n = 106/295) patients. Surgical excision was done for 34.8% (n = 85/244) of abdominal primaries, 50.0% (n = 11/22) of thoracic primaries; 22.2% (n = 2/9) neck primaries and 66.7% (n = 8/12) of the paraspinal primaries. Only 15.9% (n = 47/295) of all patients received radiotherapy. Children, who had surgery, had an improved five-year OS of 32.1% versus 5.9% without surgery (p < 0.001). Completely resected disease had a five-year OS of 30.5%, incomplete resections 31.4% versus no surgery 6.0% (p < 0.001). Radiated patients had a five-year OS of 21.3% versus 14.2% without radiotherapy (p < 0.001). Patients who received radiotherapy without surgical interventions, had a marginally better five-year OS of 12.5% as opposed to 5.4% (p < 0.001). Patients who underwent surgery had a longer mean overall survival of 60.9 months, while patients, who were irradiated, had a longer mean overall survival of 7.9 months (p < 0.001). On multivariate analysis, complete metastatic remission (p < 0.001), surgical status (p = 0.027), and radiotherapy status (p = 0.040) were significant predictive factors in abdominal primaries. CONCLUSION: Surgery and radiotherapy significantly improve outcomes regardless of the primary tumor site, emphasizing the importance of local control in neuroblastoma.


Sujet(s)
Stadification tumorale , Tumeurs du système nerveux/thérapie , Neuroblastome/thérapie , Adolescent , Biopsie , Enfant , Enfant d'âge préscolaire , Association thérapeutique/méthodes , Survie sans rechute , Femelle , Humains , Incidence , Nourrisson , Imagerie par résonance magnétique , Mâle , Tumeurs du système nerveux/diagnostic , Tumeurs du système nerveux/épidémiologie , Neuroblastome/diagnostic , Neuroblastome/épidémiologie , République d'Afrique du Sud/épidémiologie , Taux de survie/tendances , Tomodensitométrie
6.
Pediatr Hematol Oncol ; 37(4): 300-313, 2020 May.
Article de Anglais | MEDLINE | ID: mdl-32075464

RÉSUMÉ

Achieving remission after induction therapy in high-risk neuroblastoma (HR-NB) is of significant prognostic importance. This study investigated remission after induction-chemotherapy using three standard neuroblastoma protocols in the South African (SA) setting. Retrospective data of 261 patients with HR-NB diagnosed between January 2000 and December 2016, who completed induction chemotherapy with standard treatment protocols were evaluated. The treatment protocols were either OPEC/OJEC or the St Jude NB84 protocol (NB84) or rapid COJEC (rCOJEC). The postinduction metastatic complete remission (mCR) rate, 2-year overall survival (OS) and 2-year event free survival (EFS) were determined as comparative denominators. The majority (48.3%; n = 126) received OPEC/OJEC, while 70 patients received (26.8%) rCOJEC and 65 (24.9%) NB84. Treatment with NB84 had the best mCR rate (36.9%), followed by OPEC/OJEC (32.5%) and rCOJEC (21.4%). The 2-year OS of treatment with NB84 was 41% compared to OPEC/OJEC (35%) and rCOJEC (24%) (p = 0.010). The 2-year EFS of treatment with NB84 was 37% compared to OPEC/OJEC (35%) and rCOJEC (18%) (p = 0.008). OPEC/OJEC had the least treatment-related deaths (1.6%) compared to rCOJEC (7.1%) and NB84 (7.5%) (p = 0.037). On multivariate analysis LDH (p = 0.023), ferritin (p = 0.002) and INSS stage (p = 0.006) were identified as significant prognostic factors for OS. The induction chemotherapy was not significant for OS (p = 0.18), but significant for EFS (p = 0.08) Treatment with NB84 achieved better mCR, OS and EFS, while OPEC/OJEC had the least treatment-related deaths. In resource-constrained settings, OPEC/OJEC is advised as induction chemotherapy in HR-NB due to less toxicity as reflected in less treatment-related deaths.


Sujet(s)
Protocoles de polychimiothérapie antinéoplasique/administration et posologie , Chimiothérapie d'induction , Neuroblastome , Protocoles de polychimiothérapie antinéoplasique/effets indésirables , Enfant , Enfant d'âge préscolaire , Survie sans rechute , Femelle , Humains , Nourrisson , Nouveau-né , Mâle , Neuroblastome/traitement médicamenteux , Neuroblastome/mortalité , Études rétrospectives , République d'Afrique du Sud/épidémiologie , Taux de survie
7.
Pediatr Blood Cancer ; 66(11): e27944, 2019 11.
Article de Anglais | MEDLINE | ID: mdl-31368239

RÉSUMÉ

BACKGROUND: Outcome data for neuroblastoma in sub-Saharan Africa are minimal, whereas poor outcome is reported in low- and middle-income countries. A multi-institutional retrospective study across South Africa was undertaken to determine outcome. METHODS: Patients treated between January 2000 and December 2014 in nine South African pediatric oncology units were included. Kaplan-Meier curves and Cox regression models were employed to determine two-year survival rates and to identify prognostic factors. RESULTS: Data from 390 patients were analyzed. The median age was 39.9 months (range, 0-201 months). The majority presented with stage 4 disease (70%). The main chemotherapy regimens were OPEC/OJEC (44.8%), St Jude NB84 protocol (28.96%), and Rapid COJEC (22.17%). Only 44.4% had surgery across all risk groups, whereas only 16.5% of high-risk patients received radiotherapy. The two-year overall survival (OS) for the whole cohort was 37.6%: 94.1%, 81.6%, and 66.7%, respectively, for the very-low-risk, low-risk, and intermediate-risk groups and 27.6% for the high-risk group (P < 0.001, 95% CI). The median survival time for the whole group was 13 months (mean, 41.9 months; range, 0.1-209 months). MYCN-nonamplified patients had a superior two-year OS of 51.3% in comparison with MYCN-amplified patients at 37.3% (P = 0.002, 95% CI). CONCLUSIONS: Limited disease had an OS comparable with high-income countries, but advanced disease had a poor OS. South Africa should focus on early diagnosis and implementation of a national protocol with equitable access to treatment.


Sujet(s)
Neuroblastome/mortalité , Protocoles de polychimiothérapie antinéoplasique/usage thérapeutique , Enfant , Enfant d'âge préscolaire , Comorbidité , Interventions chirurgicales de cytoréduction , Pays en voie de développement , Amplification de gène , Gènes myc , Accessibilité des services de santé , Humains , Nourrisson , Nouveau-né , Estimation de Kaplan-Meier , Stadification tumorale , Neuroblastome/diagnostic , Neuroblastome/anatomopathologie , Neuroblastome/thérapie , Pronostic , Modèles des risques proportionnels , Radiothérapie/méthodes , Études rétrospectives , République d'Afrique du Sud/épidémiologie , Transplantation de cellules souches , Taux de survie , Transplantation autologue
8.
Trop Doct ; 47(4): 305-311, 2017 Oct.
Article de Anglais | MEDLINE | ID: mdl-28682220

RÉSUMÉ

Paediatric surgical disease is a neglected health problem. Patients travel great distances to tertiary level care for management. This study aimed at analysing referral patterns to design an outreach programme for paediatric surgery in KwaZulu Natal. Data forms of patients referred to the service between January and July 2016 were correlated with the clinical record. Delays in management were compared to morbidity and mortality. Out of 781, 158 referrals were accepted as emergencies. The majority (62%) were children aged < 1 year. Gastro-intestinal problems (38.4%) and congenital anomalies (26.9%) formed the majority. Patients who died had a significantly longer delay in transfer. Longer total delay was associated with statistically significant greater morbidity. In a setting where a large rural population is served by single-centre tertiary care, delays exist and contribute to morbidity. The authors advocate the establishment of an outreach programme to address these issues.


Sujet(s)
Relations communauté-institution , Interventions chirurgicales non urgentes/statistiques et données numériques , Maladies gastro-intestinales/chirurgie , Orientation vers un spécialiste/statistiques et données numériques , Soins de santé tertiaires/statistiques et données numériques , Plaies et blessures/chirurgie , , Enfant , Enfant d'âge préscolaire , Femelle , Maladies gastro-intestinales/épidémiologie , Humains , Nourrisson , Nouveau-né , Mâle , Population rurale , République d'Afrique du Sud/épidémiologie , Plaies et blessures/épidémiologie
9.
Trop Doct ; 47(4): 370-374, 2017 Oct.
Article de Anglais | MEDLINE | ID: mdl-28403698

RÉSUMÉ

Neuroblastoma is uncommon in Africa, but when seen usually presents as high-risk disease with a poor prognosis. This aggressive biology of the tumour is frequently augmented by delayed presentation. Current treatment depends upon technologies and skills that are scarce in developing countries and the cost involved is generally beyond the means of healthcare providers who are faced with a myriad more pressing healthcare issues. The presentation, treatment and outcome of 45 African children with neuroblastoma are described. Due to a lack of resources precise risk stratification was impossible but visceral or bone metastases were present in 73% of patients at diagnosis. In 91% the primary tumour was intra-abdominal. Three children (7%) were paraplegic on admission. A localised tumour was seen in one child (2%). Fifteen children (33%) underwent a surgical procedure, with intent to cure in five among whom resection was incomplete in three. For all other children, treatment was palliative using chemotherapy with judicious use of radiotherapy. Thirteen children (29%) survived longer than six months. Overall survival at three years was 4%.


Sujet(s)
Neuroblastome/épidémiologie , Afrique subsaharienne/épidémiologie , Enfant , Enfant d'âge préscolaire , Pays en voie de développement , Femelle , Humains , Nourrisson , Nouveau-né , Mâle , Neuroblastome/anatomopathologie , Neuroblastome/chirurgie , Soins palliatifs , Taux de survie
10.
Pediatr Blood Cancer ; 64(7)2017 Jul.
Article de Anglais | MEDLINE | ID: mdl-28027433

RÉSUMÉ

BACKGROUND: In developing countries up to 77% of children with cancer have been shown to be malnourished on admission. High rates of malnutrition occur due to factors such as poverty and advanced disease. Weight can be an inaccurate parameter for nutritional assessment of children with solid tumours as it is influenced by tumour mass. This study aimed to assess the prevalence of malnutrition amongst children with Wilms tumour (WT), the level of nutritional support received on admission and the influence of nutritional status on outcome. METHODS: Seventy-six children diagnosed with WT and admitted to Inkosi Albert Luthuli Central Hospital between 2004 and 2012 were studied prospectively. Nutritional assessment was conducted using weight, height, mid-upper arm circumference (MUAC) and triceps skinfold thickness (TSFT) prior to initiating treatment. Outcome was determined 2 years after admission. Time until commencement of nutritional resuscitation and nature, thereof, were recorded. RESULTS: Stunting and wasting was evident in 12% and 15% of patients, respectively. The prevalence of malnutrition was 66% when MUAC, TSFT and albumin were used. Malnutrition was not a predictor of poor outcome and did not predict advanced disease. The majority of patients (84%) received nutritional resuscitation within 2 weeks of admission. CONCLUSIONS: When classifying nutritional status in children with WT, the utilisation of weight and height in isolation can lead to an underestimation of the prevalence of malnutrition. Nutritional assessment of children with WT should also include MUAC and TSFT. Early aggressive nutritional resuscitation is recommended.


Sujet(s)
Tumeurs du rein , Malnutrition/épidémiologie , Malnutrition/étiologie , État nutritionnel , Tumeur de Wilms , Adolescent , Bras , Enfant , Enfant d'âge préscolaire , Femelle , Humains , Nourrisson , Mâle , Prévalence , Épaisseur du pli cutané , République d'Afrique du Sud
11.
S Afr Med J ; 105(11): 939-47, 2015 Nov.
Article de Anglais | MEDLINE | ID: mdl-26632323

RÉSUMÉ

BACKGROUND: Childhood cancer is an emerging problem in Africa. Its extent is hazy because data are scarce, but it should be addressed. This is the first report from the South African Children's Tumour Registry (SACTR), which covers the whole of South Africa (SA). It provides minimal estimates of cancer incidence and discusses the challenges of cancer surveillance and control in a child population in a middle-income country. Only about 2% of the African population is covered by cancer registries producing comparable incidence data. OBJECTIVE: To present and interpret incidence patterns and trends of childhood cancer over a 21-year period. The results should raise awareness of the problem of childhood cancer in an African population and provide sensible data for taking this problem in hand. METHODS: All eligible and validated cancer cases registered in the SACTR over the period 1987-2007 and classified according to the International Classification of Childhood Cancer were included. Population data were retrieved from official sources and estimated for the population subcategories. Incidence rates were standardised to the world standard and time trends were evaluated using joinpoint models, adjusting for sex and age. RESULTS: Based on the 11,699 cases, the overall age-standardised average annual incidence rate was 45 per million. Threefold differences in the overall incidence rates were observed between the ethnic groups, ranging from 116 for whites to 37 for black Africans, and they differed by diagnostic group. Differences between the nine provinces of SA relate to the ethnic composition and prevailing socioeconomic status. The overall incidence rate declined by 1.2% per year for the whole country (p<0.01). However, the decline was mainly observed during the first few years of the study period, after which rates stabilised or increased. CONCLUSIONS: Diagnosis and notification of childhood cancer should improve. The differences in incidence between ethnic groups suggest the priorities for cancer control.

12.
Int J Pediatr ; 2015: 706058, 2015.
Article de Anglais | MEDLINE | ID: mdl-25883659

RÉSUMÉ

Background. Nephroblastoma is the commonest renal tumour seen in children. It has a good prognosis in developed countries with survival rates estimated to be between 80% and 90%, while in Africa it remains low. Method. Retrospective study of patients diagnosed with nephroblastoma who are seen at 4 paediatric oncology units, representing 58.5% of all South African children with nephroblastoma and treated following SIOP protocol between January 2000 and December 2010. Results. A total of 416 patients were seen at the 4 units. Over 80% of our patients were African and almost 10% of mixed ethnicity. The most common stage was stage 4. The median survival was 28 months after diagnosis with the mixed ethnicity patients recording the longest duration (39 months) and the white patients had the shortest median survival. The overall 5-year survival rate was estimated to be 66%. Stage 2 patients did significantly better (85%). Conclusions. Our patients are similar with regard to gender ratio, median age, and age distribution as described in the literature, but in South Africa the more advanced stage disease seen than in other developed countries is translated into low overall survival rate.

13.
Semin Pediatr Surg ; 23(6): 357-62, 2014 Dec.
Article de Anglais | MEDLINE | ID: mdl-25459442

RÉSUMÉ

Peritonitis is a progressive disease leading inexorably from local peritoneal irritation to overwhelming sepsis and death unless this trajectory is interrupted by timely and effective therapy. In children peritonitis is usually secondary to intraperitoneal disease, the nature of which varies around the world. In rich countries, appendicitis is the principal cause whilst in poor countries diseases such as typhoid must be considered in the differential diagnosis. Where resources are limited, the clinical diagnosis of peritonitis mandates laparotomy for diagnosis and source control. In regions with unlimited resources, radiological investigation, ultrasound, CT scan or MRI may be used to select patients for non-operative management. For patients with appendicitis, laparoscopic surgery has achieved results comparable to open operation; however, in many centres open operation remains the standard. In complicated peritonitis "damage control surgery" may be appropriate wherein source control is undertaken as an emergency with definitive repair or reconstruction awaiting improvement in the patient's general condition. Awareness of abdominal compartment syndrome is essential. Primary peritonitis in rich countries is seen in high-risk groups, such as steroid-dependent nephrotic syndrome patients, whilst in poor countries the at-risk population is less well defined and the diagnosis is often made at surgery.


Sujet(s)
Infections intra-abdominales , Sepsie , Humains , Infections intra-abdominales/épidémiologie , Infections intra-abdominales/étiologie , Infections intra-abdominales/chirurgie , Sepsie/épidémiologie , Sepsie/étiologie , Sepsie/chirurgie
14.
Pediatr Blood Cancer ; 61(6): 987-9, 2014 Jun.
Article de Anglais | MEDLINE | ID: mdl-24453084

RÉSUMÉ

BACKGROUND: Patients under age 4 with stage I favorable histology (FH) Wilms tumor have a reported survival advantage. Among children above 10 years, a poorer prognosis has been associated with a higher prevalence of diffuse anaplasia. PURPOSE: To determine if, in our practice, patients with Wilms tumors >8 years of age (stage II-V) have a poorer prognosis than those aged <8 years or <4 years. PROCEDURE: Case-control study of 19 patients >8 years with Wilms tumor stages II-V who were identified from a cohort of 192 new patients (2002-2012). For each patient two controls were chosen matched for stage and histology, one 0-3 years and one 4-7 years. Neo-adjuvant chemotherapy was offered to all, combined with intensive supportive care. Postoperative treatment was determined by local stage and histology. OS and EFS at 5 years for the different age groups were compared. RESULTS: Each age group contained 19 patients, of whom 6 had stage II tumors, 3 stage III, 8 stage IV, and 2 stage V. Histology was intermediate risk (IR) in 17 and high risk (HR) in 2. OS at 5 years was 80.8% and EFS was 79.2% for the whole group. No significant difference in outcome could be shown between age groups. Loss to follow up was 6/57 (11%). CONCLUSIONS: The survival advantage of young age (<4 years) associated with stage I FH could not be demonstrated in higher stages. Age had no significant impact on prognosis although a trend to better outcome was seen in children <4 years.


Sujet(s)
Facteurs âges , Tumeurs du rein/mortalité , Tumeur de Wilms/mortalité , Protocoles de polychimiothérapie antinéoplasique/usage thérapeutique , Études cas-témoins , Enfant , Enfant d'âge préscolaire , Association thérapeutique , Survie sans rechute , Femelle , Humains , Nourrisson , Estimation de Kaplan-Meier , Tumeurs du rein/traitement médicamenteux , Tumeurs du rein/anatomopathologie , Tumeurs du rein/chirurgie , Mâle , Traitement néoadjuvant , Stadification tumorale , Néphrectomie , Pronostic , Études rétrospectives , République d'Afrique du Sud/épidémiologie , Résultat thérapeutique , Tumeur de Wilms/traitement médicamenteux , Tumeur de Wilms/anatomopathologie , Tumeur de Wilms/chirurgie
15.
Am J Transplant ; 14(2): 284-94, 2014 Feb.
Article de Anglais | MEDLINE | ID: mdl-24410909

RÉSUMÉ

We utilized mouse models to elucidate the immunologic mechanisms of functional graft loss during mixed antibody-mediated rejection of renal allografts (mixed AMR), in which humoral and cellular responses to the graft occur concomitantly. Although the majority of T cells in the graft at the time of rejection were CD8 T cells with only a minor population of CD4 T cells, depletion of CD4 but not CD8 cells prevented acute graft loss during mixed AMR. CD4 depletion eliminated antidonor alloantibodies and conferred protection from destruction of renal allografts. ELISPOT revealed that CD4 T effectors responded to donor alloantigens by both the direct and indirect pathways of allorecognition. In transfer studies, CD4 T effectors primed to donor alloantigens were highly effective at promoting acute graft dysfunction, and exhibited the attributes of effector T cells. Laser capture microdissection and confirmatory immunostaining studies revealed that CD4 T cells infiltrating the graft produced effector molecules with graft destructive potential. Bioluminescent imaging confirmed that CD4 T effectors traffic to the graft site in immune replete hosts. These data document that host CD4 T cells can promote acute dysfunction of renal allografts by directly mediating graft injury in addition to facilitating antidonor alloantibody responses.


Sujet(s)
Lymphocytes T CD4+/immunologie , Lymphocytes T CD8+/immunologie , Rejet du greffon/étiologie , Alloanticorps/immunologie , Isoantigènes/immunologie , Maladies du rein/immunologie , Transplantation rénale/effets indésirables , Animaux , Cytométrie en flux , Maladies du rein/complications , Maladies du rein/chirurgie , Microdissection au laser , Déplétion lymphocytaire , Souris , Souris de lignée BALB C , Souris de lignée C57BL , Souris de lignée DBA , Souris knockout , Souris transgéniques , Transplantation homologue
16.
Trop Doct ; 43(1): 1-4, 2013 Jan.
Article de Anglais | MEDLINE | ID: mdl-23550196

RÉSUMÉ

We investigated the causes, management and outcome of head injuries in paediatric patients admitted to the paediatric surgery unit at King Edward VIII Hospital over a 3-year period, from 1999 to 2001. There were 506 patients (331 male; M:F ratio 2:1) and the mean age was 71.99 +36.8 months (2 weeks to 180 months). The injuries were due to: motor vehicle crashes (324); falls (121); assault (30); inadvertent injury (23); and unknown (11). Forty-nine patients (9%) were admitted with a Glasgow Coma Scale ≤8. The most common intracranial pathology on computed tomography was: intracranial haematoma/haemorrhage (44); contusion (16); and brain oedema (10). Nineteen patients (3.4%) underwent neurosurgical intervention and the rest were managed conservatively. Eighteen died in hospital (3.6%). The mean hospital stay was 5 ± 12 days. Twenty-three patients (4.5%) were discharged with neurological sequelae. Few paediatric patients are admitted with severe head injury: the majority from blunt injury caused by motor vehicle crashes. Management mainly requires simple neurological observation in a general ward with a surprisingly good prognosis. Specific protocols for paediatric head injuries have been proposed based on these findings.


Sujet(s)
Traumatismes cranioencéphaliques , Adolescent , Enfant , Enfant d'âge préscolaire , Traumatismes cranioencéphaliques/épidémiologie , Traumatismes cranioencéphaliques/étiologie , Traumatismes cranioencéphaliques/thérapie , Pays en voie de développement , Femelle , Échelle de coma de Glasgow , Hospitalisation , Humains , Nourrisson , Nouveau-né , Mâle , Études rétrospectives , République d'Afrique du Sud/épidémiologie
17.
Pediatr Surg Int ; 29(5): 419-23, 2013 May.
Article de Anglais | MEDLINE | ID: mdl-23456286

RÉSUMÉ

PURPOSE: To present our experience of 20 children with bilateral Wilms' tumour seen in a resource-challenged environment over a 10-year period. METHOD: All patients with a diagnosis of bilateral synchronous Wilms' tumour were identified and recruited. RESULTS: Study patients represented 11 % of a cohort of 177 new patients with Wilms' tumour seen over the same period. Three patients had a syndromic predisposition to Wilms' tumour. Metastatic disease was seen at presentation in four patients (20 %) and three children presented with unilateral tumour rupture. One patient presented with paraplegia and one with obstruction of the duodenum. All children received neoadjuvant chemotherapy. One HIV-infected child died of IRIS after neoadjuvant treatment, but before surgery. One child died of progressive disease after unilateral nephrectomy. Nephron-sparing surgery was performed in 22 kidneys and 15 kidneys were removed in toto. Following enucleation of tumours, three children had positive margins. Discordant histopathology was seen in 53 % of patients. Overall survival at 2 years is 85 %. CONCLUSION: Despite significant co-morbidity and advanced disease, bilateral Wilms' tumour is a treatable disease in a resource-constrained environment.


Sujet(s)
Tumeurs du rein/chirurgie , Tumeurs primitives multiples/chirurgie , Tumeur de Wilms/chirurgie , Traitement médicamenteux adjuvant , Enfant , Enfant d'âge préscolaire , Pays en voie de développement , Femelle , Humains , Nourrisson , Tumeurs du rein/mortalité , Tumeurs du rein/anatomopathologie , Mâle , Tumeurs primitives multiples/mortalité , Tumeurs primitives multiples/anatomopathologie , Complications postopératoires/épidémiologie , Analyse de survie , Tumeur de Wilms/mortalité , Tumeur de Wilms/secondaire
18.
Clin Transplant ; 26(4): E402-11, 2012.
Article de Anglais | MEDLINE | ID: mdl-22882695

RÉSUMÉ

BACKGROUND: Acute allograft rejection after HLA desensitization is common early post-transplant but the sequence of histopathologic changes leading to graft dysfunction has not been well defined. METHODS: We evaluated the early pathogenesis and sequence of antibody-mediated graft damage of 35 desensitized living donor kidney recipients by studying the course of biopsies taken in the very early post-transplant period (<1 month). RESULTS: A total of 14 of the 35 patients met criteria for acute antibody-mediated rejection (AMR). In these patients, the chronologic sequence of pathologic changes was C4d peritubular capillary deposition, acute tubular injury, and peritubular capillaritis, followed by glomerulitis and interstitial inflammation. Classic AMR lesions occurred early, followed by mononuclear cellular infiltration, which comprised CD4 and CD8 T cells and monocytes. Development of graft dysfunction in most patients occurred concurrently with the emergence of graft cellular infiltration, rather than at the earlier time of antibody deposition as detected via C4d deposition. CONCLUSION: These data provide novel insight into the sequence of pathologic changes in patients with AMR post-transplant after HLA desensitization.


Sujet(s)
Désensibilisation immunologique , Rejet du greffon/immunologie , Rejet du greffon/anatomopathologie , Antigènes HLA/immunologie , Alloanticorps/immunologie , Transplantation rénale/immunologie , Transplantation rénale/anatomopathologie , Cytométrie en flux , Études de suivi , Humains , Alloanticorps/sang , Pronostic , Études rétrospectives , Transplantation homologue
19.
Pediatr Blood Cancer ; 59(2): 391-4, 2012 Aug.
Article de Anglais | MEDLINE | ID: mdl-22315136

RÉSUMÉ

BACKGROUND: From Africa, where socio-economic circumstances differ from the developed world, there are no data regarding the influence of liver metastases on survival of children with Wilms tumour. PROCEDURE: One hundred fifty new patients with WT were seen between 2002 and 2010, 45 (30%) had metastases at diagnosis. Seven patients had bilateral disease with additional visceral metastases. Nine patients who developed liver metastases during treatment were excluded. The site of metastases and the results of pretreatment biopsies were retrieved. Neo-adjuvant chemotherapy was combined with nutritional resuscitation, and aggressive supportive care. Post-operative treatment was determined by stage and histology. RESULTS: Liver metastases were present in 19 (42%) patients but were the sole metastatic site in only 4 (9%). Overall survival at 5 years was 58.5%. Event Free Survival was 54%. Thirty-three (73%) had favourable histology, nine unfavourable and undetermined in three. No influence of histology on outcome was evident. Three patients had resection of persistent liver metastases. The pattern of metastatic disease had no influence on outcome. Despite aggressive supportive care two patients (4%) died within a week of presentation. Two patients died of chemotoxicity and two of complications following biopsy. Eight patients (17%) were lost to follow-up of whom five were on palliative treatment only. CONCLUSIONS: In Africa liver metastases do not appear to worsen the prognosis of children with Stage IV WT. Despite the poor socio-economic circumstances survival is comparable to other countries.


Sujet(s)
Tumeurs du rein/mortalité , Tumeurs du foie/mortalité , Tumeur de Wilms/mortalité , Enfant , Enfant d'âge préscolaire , Association thérapeutique , Femelle , Humains , Nourrisson , Nouveau-né , Tumeurs du rein/anatomopathologie , Tumeurs du rein/thérapie , Tumeurs du foie/secondaire , Tumeurs du foie/thérapie , Mâle , Stadification tumorale , Pronostic , Études prospectives , Taux de survie , Tumeur de Wilms/anatomopathologie , Tumeur de Wilms/thérapie
20.
World J Surg ; 36(3): 565-72, 2012 Mar.
Article de Anglais | MEDLINE | ID: mdl-22270981

RÉSUMÉ

BACKGROUND: Pediatric non-Wilms' renal tumors (NWRT) are poorly understood owing to their heterogeneity and relative rarity. This study aimed at auditing the outcome of the management of NWRT in a tertiary hospital in the Third World. METHODS: Records of all patients (n = 68) treated for NWRT over a 32-year period (1978-2010) were reviewed retrospectively. RESULTS: The major histological groups included clear cell sarcoma of the kidney (CCSK) (33.8%), mesoblastic nephroma (17.6%), cystic partially differentiated nephroblastoma (CPDN) (17.6%), intrarenal neuroblastoma (8.8%), malignant rhabdoid tumor (MRT) (7.4%), and renal cell carcinoma (RCC) (5.9%). Sixteen (69.7%) patients with CCSK and 11 (91.7%) with CPDN were aged 1-4 years. Ten (83.3%) patients with mesoblastic nephroma were aged <1 year and three (60.0%) with RCC were aged 10-14 years. Ten (43.5%) patients with CCSK and four (80.0%) with RCC had metastases at diagnosis. The sensitivity of a pretreatment Tru-Cut biopsy was 100% for MRT. All the patients with CCSK, mesoblastic nephroma, CPDN, and RCC had radical nephrectomy. Only eight (34.8%) patients with CCSK received radiotherapy. The overall 1-10-year survival rates were 52.2%, 91.7%, 75.0%, 40.0% and 0.0% for CCSK, mesoblastic nephroma, CPDN, RCC, and MRT, respectively. The overall 1-10-year survival for the entire cohort was 51.5%. CONCLUSIONS: The demography and clinical presentation of pediatric NWRT, which comprises 13.6% of pediatric renal tumors in the Third World, were similar to those in the Developed World. The overall 1-10-year survival for pediatric NWRT was low.


Sujet(s)
Tumeurs du rein/chirurgie , Sarcome à cellules claires/chirurgie , Adolescent , Néphrocarcinome/chirurgie , Traitement médicamenteux adjuvant , Enfant , Enfant d'âge préscolaire , Humains , Nourrisson , Tumeurs du rein/mortalité , Tumeurs du rein/thérapie , Traitement néoadjuvant , Néphrome mésoblastique/chirurgie , Études rétrospectives , Tumeur de Wilms/chirurgie
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