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Background and Aims: The coronavirus disease 2019 (COVID-19) pandemic stimulated a paradigm shift in medical and surgical education from in-person teaching to online teaching. It is unclear whether an in-person or online approach to surgical teaching for medical students is superior. We aim to compare the outcomes of in-person versus online surgical teaching in generating interest in and improving knowledge of surgery in medical students. We also aim the quantify the impact of a peer-run surgical teaching course. Methods: A six-session course was developed by medical students and covered various introductory surgical topics. The first iteration was offered online to 70 UK medical students in March 2021, and the second iteration was in-person for 20 students in November 2021. Objective and subjective knowledge was assessed through questionnaires before and after each session, and also for the entire course. Data were analyzed from this mixed-methods study to compare the impact of online versus in-person teaching on surgical knowledge and engagement. Results: Students in both iterations showed significant improvement of 33%-282% across the six sessions in knowledge and confidence after completing the course (p < 0.001). There was no significant difference in the level of objective knowledge, enjoyment, or organization of the course between online and in-person groups, although the in-person course was rated as more engaging (mean Likert score 9.1 vs. 9.7, p = 0.033). Discussion: Similar objective and subjective surgical teaching outcomes were achieved in both iterations, including in "hands-on" topics such as suturing, gowning, and gloving. Students who completed the online course did not have any lower knowledge or confidence in their surgical skills; however, the in-person course was reported to be more engaging. Surgical teaching online and in-person may be similarly effective and can be delivered according to what is most convenient for the circumstances, such as in COVID-19.
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BACKGROUND: The variations in outcome and frequent occurrence of kidney allograft failure continue to pose important clinical and research challenges despite recent advances in kidney transplantation. The aim of this systematic review was to examine the current application of machine learning models in kidney transplantation and perform a meta-analysis of these models in the prediction of graft survival. METHODS: This review was registered with the PROSPERO database (CRD42021247469) and all peer-reviewed original articles that reported machine learning model-based prediction of graft survival were included. Quality assessment was performed by the criteria defined by Qiao and risk-of-bias assessment was performed using the PROBAST tool. The diagnostic performance of the meta-analysis was assessed by a meta-analysis of the area under the receiver operating characteristic curve and a hierarchical summary receiver operating characteristic plot. RESULTS: A total of 31 studies met the inclusion criteria for the review and 27 studies were included in the meta-analysis. Twenty-nine different machine learning models were used to predict graft survival in the included studies. Nine studies compared the predictive performance of machine learning models with traditional regression methods. Five studies had a high risk of bias and three studies had an unclear risk of bias. The area under the hierarchical summary receiver operating characteristic curve was 0.82 and the summary sensitivity and specificity of machine learning-based models were 0.81 (95 per cent c.i. 0.76 to 0.86) and 0.81 (95 per cent c.i. 0.74 to 0.86) respectively for the overall model. The diagnostic odds ratio for the overall model was 18.24 (95 per cent c.i. 11.00 to 30.16) and 29.27 (95 per cent c.i. 13.22 to 44.46) based on the sensitivity analyses. CONCLUSION: Prediction models using machine learning methods may improve the prediction of outcomes after kidney transplantation by the integration of the vast amounts of non-linear data.
Subject(s)
Kidney Transplantation , Renal Insufficiency , Humans , Kidney Transplantation/adverse effects , Graft Survival , Sensitivity and Specificity , ROC Curve , Machine LearningABSTRACT
BACKGROUND: We used the BSAi (Donor BSA/Recipient BSA) to assess whether transplanting a small or large kidney into a pediatric recipient relative to his/her size influences renal transplant outcomes. METHODS: We included 14 322 single-kidney transplants in pediatric recipients (0-17 years old) (01/2000-02/2020) from the United Network for Organ Sharing database. We divided cases into four BSAi groups (BSAi ≤ 1, 1 < BSAi ≤ 2, 2 < BSAi ≤ 3, BSAi > 3). RESULTS: There were no differences concerning delayed graft function (DGF) or primary non-function (PNF) rates, whether the grafts were from living or brain-dead donors. In both transplants coming from living donors and brain-dead donors, cases with BSAi > 3 and cases with 2 < BSAi ≤ 3 had similar graft survival (p = .13 for transplants from living donors, p = .413 for transplants from brain-dead donors), and both groups had longer graft survival than cases with 1 < BSAi ≤ 2 and cases with BSAi ≤ 1 (p < .001). The difference in 10-year graft survival rates between cases with BSAi > 3 and cases with BSAi ≤ 1 reached around 25% in both donor types. The better graft survival in transplants with BSAi > 2 was confirmed in multivariable analysis. CONCLUSIONS: There is no significant impact of donor-recipient size mismatch on DGF and PNF rates in pediatric renal transplants. However, graft survival is significantly improved when the donor's size is more than twice the pediatric recipient's size.
Subject(s)
Kidney Diseases , Kidney Transplantation , Humans , Child , Male , Female , Infant, Newborn , Infant , Child, Preschool , Adolescent , Tissue Donors , Living Donors , Graft Survival , Survival Rate , Brain Death , RegistriesABSTRACT
Renal artery aneurysmal (RAA) disease is a rare, but potentially life-threatening cause of renovascular disease presenting with hypertension. Conventional management involves aneurysmal excision followed by renal auto-transplantation. We present the management of a 13-year-old girl with complex multiple saccular aneurysmal disease of the left renal artery with hilar extension and symptomatic hypertension. We used 3D printing to print a patient-specific model that was not implanted in the patient but was used for surgical planning and discussion with the patient and their family. Endovascular options were precluded due to anatomical complexities. Following multi-disciplinary review and patient-specific 3D printing, she underwent successful in-situ RAA repair with intraoperative cooling, without the need for auto-transplantation. 3D printing enabled appreciation of aneurysmal spatial configuration and dimensions that also helped plan the interposition graft length needed following aneurysmal excision. The models provided informed multidisciplinary communications and proved valuable during the consent process with the family for this high-risk procedure. To our knowledge, this is the first reported case utilizing 3D printing to facilitate in-situ complex repair of RAA with intra-hilar extension for paediatric renovascular disease.
Subject(s)
Aneurysm , Hypertension, Renovascular , Hypertension , Kidney Diseases , Female , Humans , Child , Adolescent , Renal Artery/surgery , Aneurysm/diagnostic imaging , Aneurysm/surgery , Aneurysm/complications , Hypertension, Renovascular/etiology , Kidney Diseases/complications , Printing, Three-DimensionalABSTRACT
BACKGROUND: Transplant rejection is a major cause of graft loss and morbidity. Currently, no human models of antibody-mediated rejection (AMR) exist, limiting mechanistic investigation and organ-specific targeted therapy. Here, using 12 human kidneys and ex-vivo normothermic machine perfusion, we demonstrate phenotypes of AMR after addition of antibodies against either human HLA class I or blood group antigens (A, B), thus modelling clinical AMR that can follow HLA incompatible (HLAi) or blood group incompatible (ABOi) transplantation. METHODS: Discarded human kidneys with wide ranging demographics and cold ischaemia times (11-54 h) were perfused with red blood cells and fresh frozen plasma (FFP) as a source of complement/coagulation factors. For the HLAi model, 600 µg of W6/32 anti-class 1 HLA antibody was added to the circuit (time '0'). For the ABOi model, high titre FFP of the relevant blood group antibody was added. Renal blood flow index (RBFi, mL/min/100 g), C3 desArg, prothrombin fragments 1 + 2 and histology were determined. Our endpoints included haemodynamic changes, thrombosis, and biopsy proven complement deposition. FINDINGS: Compared to control kidneys perfused without anti-donor antibodies, both models demonstrated haemodynamic collapse after antibody perfusion with only the HLAi model showing glomerular C4d deposition. INTERPRETATION: We show that a clinically relevant human kidney model of AMR is feasible, and anticipate that these models, with refinements, could provide a basis to test different strategies to prevent AMR. FUNDING: The Rosetrees and Stonygate Trust, The Royal College of Surgeons of England Fellowship Grant, NIHR Biomedical Research Centre/KCL Early Career Grant, Kidney Research U.K.
Subject(s)
Kidney Transplantation , Humans , Kidney Transplantation/adverse effects , HLA Antigens , ABO Blood-Group System , Graft Rejection , Antibodies , Kidney/pathology , PerfusionABSTRACT
The incidence of incisional hernia after kidney transplantation varies between 1.1% and 3.8%. These are usually repaired electively using polypropylene mesh. We present here a case where a patient presented as an emergency, with a large painful incisional hernia over his kidney transplant, and evidence of local erythema and systemic inflammation. As this could have represented either infection or rejection, the patient was started on antibiotics and subsequently underwent graft nephrectomy and hernia repair using a biological (porcine-derived) acellular dermal matrix, Strattice™, with a satisfactory outcome. In addition, histology showed evidence of allograft rejection. This is the first reported case of an incisional hernia containing a rejecting kidney allograft, managed with nephrectomy and biological mesh repair.
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BACKGROUND: Postoperative infection after hand-assisted laparoscopic donor nephrectomy (HALDN) confers significant morbidity to a healthy patient group. Current UK guidelines cite a lack of evidence for routine antibiotic prophylaxis. This trial assessed if a single preoperative antibiotic dose could reduce post HALDN infections. METHODS: Eligible donors were randomly and blindly allocated to preoperative single-dose intravenous co-amoxiclav or saline. The primary composite endpoint was clinical evidence of any postoperative infection at 30 days, including surgical site infection (SSI), urinary tract infection (UTI), and lower respiratory tract infection (LRTI). FINDINGS: In all, 293 participants underwent HALDN (148 antibiotic arm and 145 placebo arm). Among them, 99% (291/293) completed follow-up. The total infection rate was 40.7% (59/145) in the placebo group and 23% (34 of 148) in the antibiotic group (P = 0.001). Superficial SSIs were 20.7% (30/145 patients) in the placebo group versus 10.1% (15/148 patients) in the antibiotic group (P = 0.012). LRTIs were 9% (13/145) in the placebo group and 3.4% (5/148) in the antibiotic group (P = 0.046). UTIs were 4.1% (6/145) in the placebo group and 3.4% (5/148) in the antibiotic group (P = 0.72).Antibiotic prophylaxis conferred a 17.7% (95% confidence interval 7.2%-28.1%), absolute risk reduction in developing postoperative infection, with 6 donors requiring treatment to prevent 1 infection. INTERPRETATION: Single-dose preoperative antibiotic prophylaxis dramatically reduces post-HALDN infection rates, mainly impacting SSIs and LRTIs.
Subject(s)
Amoxicillin-Potassium Clavulanate Combination/administration & dosage , Antibiotic Prophylaxis , Living Donors , Nephrectomy , Surgical Wound Infection/prevention & control , Adult , Double-Blind Method , Female , Humans , Laparoscopy , Male , Middle Aged , Respiratory Tract Infections/prevention & control , United Kingdom , Urinary Tract Infections/prevention & controlABSTRACT
International guidelines recommend colonoscopy following hospitalisation for acute diverticulitis. There is a paucity of evidence supporting the efficacy of colonoscopy in this context, particularly for patients with CT-diagnosed uncomplicated left-sided diverticulitis. This study aims to investigate the frequency that colorectal cancer (CRC) and advanced adenomas (AA) are identified during follow-up colonoscopy after hospitalisation with CT-proven left-sided diverticulitis for the first time in a UK population. In this single-centre retrospective-cohort study all patients presenting with CT-diagnosed uncomplicated left-sided diverticulitis between 2014 and 2017 were identified. The incidence of histologically confirmed CRC and AA identified at follow-up colonoscopy 4-6 weeks following discharge was assessed. 204 patients with CT proven uncomplicated left-sided diverticulitis underwent follow-up colonoscopy. 72% were female and the median age was 63 years. There were no major complications. 22% of patients were found to have incidental hyperplastic polyps or adenomas with low-grade dysplasia. No CRC or AA were found. Routine colonoscopy following acute diverticulitis in this cohort did not identify a single CRC or AA and could arguably have been omitted. This would significantly reduce cost and pressure on endoscopy departments, in addition to the pain and discomfort that is commonly associated with colonoscopy.
Subject(s)
Colonoscopy , Diverticulitis, Colonic/diagnosis , Tomography, X-Ray Computed , Acute Disease , Adult , Aged , Aged, 80 and over , Comorbidity , Disease Management , Female , Follow-Up Studies , Humans , Male , Middle Aged , Retrospective StudiesABSTRACT
Ex vivo normothermic perfusion (EVNP) technology is a promising means of organ preservation, assessment, and preconditioning prior to kidney transplantation, which has been pioneered by a single group. We describe the challenges of setting up clinical EVNP programs in 2 new centers, as well as early patient outcomes. Governance, training, and logistical pathways are described. In order to demonstrate safety and proficiency in this new technique, early patient outcomes are also described. Patient outcomes included the incidence of primary nonfunction, delayed graft function, graft and patient survival at 1 year. Contralateral kidneys undergoing static cold storage alone were used as a comparator group. Between March 2016 and July 2017, EVNP was performed on 14 kidneys from 12 donors (11 kidneys in center 1, 3 kidneys in center 2). Of the 14 kidneys that underwent EVNP, 12 organs were implanted into 10 recipients. Two pairs of kidneys were implanted as dual grafts and 1 kidney was implanted simultaneously with a pancreas. The remaining 7 kidneys were transplanted as single allografts. Seven pairs of kidneys were available for paired analysis comparing EVNP versus static cold storage. Graft and patient outcomes were comparable between the 2 preservation techniques. The introduction of a clinical EVNP service requires a careful multimodal approach, drawing on the expertise of specialists in transplantation, hematology, and microbiology. Both new clinical EVNP programs demonstrated proficiency and safety when a structured dissemination process was followed.
Subject(s)
Kidney Transplantation , Kidney/physiology , Organ Preservation/instrumentation , Perfusion/instrumentation , Adult , Equipment Design , Humans , Kidney Transplantation/methods , Organ Preservation/methods , Perfusion/methods , Tissue DonorsABSTRACT
OBJECTIVE: The authors investigated a novel application of patient-specific three-dimensional (3D) printing, to enhance preoperative, multidisciplinary planning in complex, living-donor pediatric renal transplantation. SUMMARY BACKGROUND DATA: For children with end-stage kidney disease, the transplantation of adult-sized, living-donor kidneys into small recipients (<20âkg) with increasingly complex structural anomalies can be difficult. Establishing the operative feasibility in such cases demands a surgical understanding of anatomy to be derived from medical imaging. However, this is hampered by the representation of complex structures in 2D, the inherent interpretive expertise this demands, and the challenge of conveying this appreciation to others. METHODS: We report the novel use of patient-specific 3D printed models to achieve personalized management for 3 children who underwent living-donor renal transplantation. Each presented a unique surgical challenge that would otherwise prevent preoperative determination of transplantation feasibility. Patient-specific geometries were segmented from imaging data and fabricated using polyjet, 3D printing technology. Models were verified by an expert radiologist and presented during multidisciplinary discussion and surgical simulation. RESULTS: 3D printed models enhanced preoperative deliberation and surgical simulation and allowed on-table exploration of a small child to be avoided. We have critically determined specific clinical indications, technical insights, limitations, and outcomes of this approach. At latest follow-up (>16 mo) all patients remain well with functioning renal allografts. CONCLUSIONS: We report the new and safe integration of patient-specific 3D printing into complex pediatric renal transplantation. This technique enhances surgical planning and can inform operative feasibility in those cases which would otherwise be uncertain.
Subject(s)
Kidney Transplantation/methods , Printing, Three-Dimensional , Adult , Age Factors , Child , Child, Preschool , Humans , Kidney/anatomy & histology , Kidney/surgery , Organ SizeABSTRACT
INTRODUCTION: Robotic surgery has been increasingly used in fashioning various surgical anastomoses. Our aim was to collect and analyze outcomes related to anastomoses performed using a robotic approach and compare them with those done using laparoscopic or open approaches through meta-analysis. METHODS: A systematic review was conducted for articles comparing robotic with laparoscopic and/or open operations (colectomy, low anterior resection, gastrectomy, Roux-en-Y gastric bypass (RYGB), pancreaticoduodenectomy, radical cystectomy, pyeloplasty, radical prostatectomy, renal transplant) published up to June 2019 searching Medline, Scopus, Google Scholar, Clinical Trials and the Cochrane Central Register of Controlled Trials. Studies containing information about outcomes related to hand-sewn anastomoses were included for meta-analysis. Studies with stapled anastomoses or without relevant information about the anastomotic technique were excluded. We also excluded studies in which the anastomoses were performed extracorporeally in laparoscopic or robotic operations. RESULTS: We included 83 studies referring to the aforementioned operations (4 randomized controlled and 79 non-randomized, 10 prospective and 69 retrospective) apart from colectomy and low anterior resection. Anastomoses done using robotic instruments provided similar results to those done using laparoscopic or open approach in regards to anastomotic leak or stricture. However, there were lower rates of stenosis in robotic than in laparoscopic RYGB (p=0.01) and in robotic than in open radical prostatectomy (p<0.00001). Moreover, all anastomoses needed more time to be performed using the robotic rather than the open approach in renal transplant (p≤0.001). CONCLUSION: Robotic anastomoses provide equal outcomes with laparoscopic and open ones in most operations, with a few notable exceptions.
Subject(s)
Printing, Three-Dimensional , Prostatectomy/methods , Prostatic Neoplasms/surgery , Robotic Surgical Procedures/methods , Aged , Follow-Up Studies , Humans , Magnetic Resonance Imaging/methods , Male , Middle Aged , Models, Anatomic , Pilot Projects , Prospective Studies , Prostate/pathology , Prostate/surgeryABSTRACT
Robotic-assisted kidney transplantation (RAKT) offers key benefits for patients that have been demonstrated in several studies. A barrier to the wider uptake of RAKT is surgical skill acquisition. This is exacerbated by the challenges of modern surgery with reduced surgical training time, patient safety concerns and financial pressures. Simulation is a well-established method of developing surgical skill in a safe and controlled environment away from the patient. We have developed a 3D printed simulation model for the key step of the kidney transplant operation which is the vascular anastomosis. The model is anatomically accurate, based on the CT scans of patients and it incorporates deceased donor vascular tissue. Crucially, it was developed to be used in the robotic operating theatre with the operating robot to enhance its fidelity. It is portable and relatively inexpensive when compared with other forms of simulation such as virtual reality or animal lab training. It thus has the potential of being more accessible as a training tool for the safe acquisition of RAKT specific skills. We demonstrate this model here.
Subject(s)
Kidney Transplantation/instrumentation , Models, Anatomic , Printing, Three-Dimensional , Robotic Surgical Procedures/instrumentation , Equipment Design , Humans , Kidney Transplantation/methods , Robotic Surgical Procedures/methodsABSTRACT
BACKGROUND: Children with end-stage kidney disease may have coexisting iatrogenic or congenital vascular anomalies making transplantation difficult. We describe our approach in 5 recipients with vascular anomalies and significant comorbidities, including one case of blood group incompatibility. METHODS: Five children aged 3 to 17 years (median, 7 years), weighing 14 to 34 kg (median, 18 kg) kg of whom 4 had occluded inferior vena cava or iliac veins and 2 had previous complex vascular reconstructions before transplantation for midaortic syndrome and multiple aortic aneurysms, respectively underwent renal transplantation. To establish implant feasibility surgery was commenced in 2 recipients before the donor surgery. RESULTS: There was 4 (80%) of 5 patient survival after 1 death from sepsis (with a functioning graft) and 2 cases of delayed graft function. At the latest median follow-up of 19 months, there was 100% (death-censored) renal allograft survival with estimated glomerular filtration rates (mL/min per 1.73 m) of 43 to 72 (median, 55). CONCLUSIONS: We conclude that major vascular anomalies do not necessarily preclude transplantation in complex pediatric patients and that surgical exploration of the recipient before commencing the donor surgery is valuable where feasibility and safety are uncertain. In addition, we have developed a novel classification system of congenital vascular abnormalities and propose its use in complex pediatric transplantation.
Subject(s)
Kidney Failure, Chronic/surgery , Kidney Transplantation/methods , Tissue Donors , Transplant Recipients , Vascular Malformations/complications , Adolescent , Child , Child, Preschool , Fatal Outcome , Female , Follow-Up Studies , Graft Survival , Humans , Kidney Failure, Chronic/complications , Male , Middle Aged , Time Factors , Transplantation, HomologousABSTRACT
BACKGROUND: Blood group incompatible transplantation (ABOi) in children is rare as pretransplant conditioning remains challenging and concerns persist about the potential increased risk of rejection. METHODS: We describe the results of 11 ABOi pediatric renal transplant recipients in the 2 largest centers in the United Kingdom, sharing the same tailored desensitization protocol. Patients with pretransplant titers of 1 or more in 8 received rituximab 1 month before transplant; tacrolimus and mycophenolate mofetil were started 1 week before surgery. Antibody removal was performed to reduce titers to 1 or less in 8 on the day of the operation. No routine postoperative antibody removal was performed. RESULTS: Death-censored graft survival at last follow-up was 100% in the ABOi and 98% in 50 compatible pediatric transplants. One patient developed grade 2A rejection successfully treated with antithymocyte globulin. Another patient had a titer rise of 2 dilutions treated with 1 immunoadsorption session. There was no histological evidence of rejection in the other 9 patients. One patient developed cytomegalovirus and BK and 2 others EBV and BK viremia. CONCLUSIONS: Tailored desensitization in pediatric blood group incompatible kidney transplantation results in excellent outcomes with graft survival and rejection rates comparable with compatible transplants.
Subject(s)
ABO Blood-Group System/immunology , Blood Group Incompatibility/drug therapy , Desensitization, Immunologic/methods , Graft Rejection/prevention & control , Histocompatibility , Immunosuppressive Agents/administration & dosage , Kidney Transplantation/methods , Adolescent , Age Factors , Blood Group Incompatibility/immunology , Blood Group Incompatibility/mortality , Child , Child, Preschool , Desensitization, Immunologic/adverse effects , Desensitization, Immunologic/mortality , Disease-Free Survival , Drug Therapy, Combination , Female , Graft Rejection/immunology , Graft Rejection/mortality , Graft Survival/drug effects , Humans , Immunosuppressive Agents/adverse effects , Kaplan-Meier Estimate , Kidney Transplantation/adverse effects , Kidney Transplantation/mortality , London , Male , Mycophenolic Acid/administration & dosage , Risk Factors , Rituximab/administration & dosage , Tacrolimus/administration & dosage , Time Factors , Treatment OutcomeABSTRACT
INTRODUCTION: We present a case of primary gastrointestinal tuberculosis that has culminated in ulcer formation, in the absence of pulmonary involvement in an immunocompetent patient. PRESENTATION OF CASE: A 28-year-old Asian male presented to casualty with a 1-week history of epigastric cramping abdominal pain and several episodes of non-bilious vomiting. The patient deteriorated clinically, becoming more cachectic and given his unexplained weight loss, an oesophageal-gastro-duodenal endoscopic imaging confirmed a duodenal ulcer. The biopsy of the non-healing ulcer was the hallmark of the disease, revealing evidence of granulomatous inflammation consistent with tuberculosis bacilli. DISCUSSION: Gastrointestinal tuberculosis with ulceration is rare with respect to the oesophagus, stomach and duodenum. This case proves to be unique, as our patient had experienced primary isolated gastric tuberculosis in the absence of pulmonary tuberculosis in a healthy individual. Immunohistochemical staining, histopathology and radiological investigations have demonstrated their importance in confirming abdominal tuberculosis and the extent of bowel involvement. CONCLUSION: This case has illustrated the difficulties associated with a prompt diagnosis of an unusual case of primary duodenal tuberculosis from chronic peptic ulcer disease in an immunocompetent patient.
Subject(s)
Aneurysm, Infected/surgery , Kidney Transplantation/methods , Renal Artery/surgery , Adult , Allografts , Anastomosis, Surgical , Gout/therapy , Humans , Hyperuricemia/therapy , Iliac Artery/surgery , Inflammation , Kidney Diseases/therapy , Kidney Failure, Chronic/therapy , Male , Meropenem , Postoperative Complications , Teicoplanin/therapeutic use , Thienamycins/therapeutic use , Treatment OutcomeABSTRACT
BACKGROUND: The sequestration of Plasmodium falciparum-infected erythrocytes in brain microvasculature through cytoadherence to endothelium, is the hallmark of the definitive diagnosis of cerebral malaria and plays a critical role in malaria pathogenesis. The complex pathophysiology, which leads each patient to the final outcome of cerebral malaria, is multifaceted and thus, metrics to delineate specific patterns within cerebral malaria are needed to further parse patients. METHODS: A method was developed for quantification utilizing counts of capillary contents (early-stage parasites, late-stage parasites and fibrin) from histological preparations of brain tissue after death, and compared it to the standard approach, in which the percentage of parasitized vessels in cross-section is determined. RESULTS: Within the initial cohort of 50 patients, two different observers agreed closely on the percentage of vessels parasitized, pigmented parasites and pigment globules (ICC = 0.795-0.970). Correlations between observers for correct diagnostic classification were high (Kendall's tau-b = 0.8779, Kappa = 0.8413). When these methods were applied prospectively to a second set of 50 autopsy samples, they revealed a heterogeneous distribution of sequestered parasites in the brain with pigmented parasites and pigment globules present in the cerebellum > cortex > brainstem. There was no difference in the distribution of early stages of parasites or in the percentage of vessels parasitized across the same sites. The second cohort of cases was also used to test a previously published classification and regression tree (CART) analysis; the quantitative data alone were able to accurately classify and distinguish cerebral malaria from non-cerebral malaria. Classification errors occurred within a subclassification of cerebral malaria (CM1 vs CM2). A repeat CART analysis for the second cohort generated slightly different classification rules with more accurate subclassification, although misclassification still occurred. CONCLUSIONS: The traditional measure of parasite sequestration in falciparum malaria, the percentage of vessels parasitized, is the most reliable and consistent for the general diagnosis of cerebral malaria. Methods that involve quantitative measures of different life cycle stages are useful for distinguishing patterns within the cerebral malaria population; these subclassifications may be important for studies of disease pathogenesis and ancillary treatment.