The clinical utility of PET/CT scan and tissue biopsy in the management and follow-up of paediatric Hodgkin lymphoma in South Africa.

BACKGROUND: In low- to middle-income countries (LMICs) like South Africa, there is a need to understand the clinical practices surrounding diagnosis and surveillance of paediatric Hodgkin lymphoma (HL) to reduce the burden on health systems. Understanding the clinical utility of PET/CT scans may decrease repeated tissue biopsies during disease surveillance. METHODS: This is a retrospective cohort study of patients aged less than 18 years treated for HL at Chris Hani Baragwanath Academic Hospital from 1 January 2009 to 31 December 2018. RESULTS: Fifty-four patients were included in the study; male-to-female ratio was 5:1 with a mean age of 9 years. Seventy per cent of patients (n = 38) received a PET/CT and tissue biopsy during their initial diagnostic workup, whereas 20.4% (n = 11) of patients received a PET/CT and tissue biopsy during surveillance. Tissue biopsy and PET/CT showed slight agreement (κ = 0.14) in diagnosing relapsed disease during surveillance. The false negative rate for tissue biopsy during surveillance was 42.9%. Surveillance PET/CT showed a positive predictive value (PPV) of 66.7% and negative predictive value (NPV) of 100% when compared to tissue biopsy. CONCLUSION: This study is the first cohort to explore the clinical utility of PET/CT scans and tissue biopsies in a lowresourced setting. Our findings showed slight agreement between the modalities in diagnosing relapsed disease during surveillance. A portion of this discordance can be attributed to false negative tissue biopsy results. While the sample is limited, our findings are consistent with the high NPV of PET/CT scans of > 95% as is reported in the literature.

Outcomes following anterior odontoid screw versus posterior arthrodesis for odontoid fractures: a systematic review and meta-analysis.

OBJECTIVE: Odontoid fractures can be managed surgically when indicated. The most common approaches are anterior dens screw (ADS) fixation and posterior C1-C2 arthrodesis (PA). Each approach has theoretical advantages, but the optimal surgical approach remains controversial. The goal in this study was to systematically review the literature and synthesize outcomes including fusion rates, technical failures, reoperation, and 30-day mortality associated with ADS versus PA for odontoid fractures. METHODS: A systematic literature review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines by searching the PubMed, EMBASE, and Cochrane databases. A random-effects meta-analysis was performed and the I2 statistic was used to assess heterogeneity. RESULTS: In total, 22 studies comprising 963 patients (ADS 527, PA 436) were included. The average age of the patients ranged from 28 to 81.2 years across the included studies. The majority of the odontoid fractures were type II based on the Anderson-D'Alonzo classification. The ADS group was associated with statistically significantly lower odds to achieve bony fusion at last follow-up compared to the PA group (ADS 84.1%; PA 92.3%; OR 0.46; 95% CI 0.23-0.91; I2 42.6%). The ADS group was associated with statistically significantly higher odds of reoperation compared to the PA group (ADS 12.4%; PA 5.2%; OR 2.56; 95% CI 1.50-4.35; I2 0%). The rates of technical failure (ADS 2.3%; PA 1.1%; OR 1.11; 95% CI 0.52-2.37; I2 0%) and all-cause mortality (ADS 6%; PA 4.8%; OR 1.35; 95% CI 0.67-2.74; I2 0%) were similar between the two groups. In the subgroup analysis of patients > 60 years old, the ADS was associated with statistically significantly lower odds of fusion compared to the PA group (ADS 72.4%; PA 89.9%; OR 0.24; 95% CI 0.06-0.91; I2 58.7%). CONCLUSIONS: ADS fixation is associated with statistically significantly lower odds of fusion at last follow-up and higher odds of reoperation compared to PA. No differences were identified in the rates of technical failure and all-cause mortality. Patients receiving ADS fixation at > 60 years old had significantly higher and lower odds of reoperation and fusion, respectively, compared to the PA group. PA is preferred to ADS fixation for odontoid fractures, with a stronger effect size for patients > 60 years old.

Burn-injured patients - the preferably unheard.

BACKGROUND: Data on colorectal cancer (CRC) diagnosis to treatment interval (DTI), an index of quality assurance in high-income countries (HICs) is lacking in South Africa. This study aimed to determine DTIs and their impact on CRC survival in a South African cohort. METHODS: Participants (n = 289) from the Colorectal Cancer in South Africa (CRCSA) cohort were identified for inclusion. The DTI was defined as the duration between the diagnosis and initial definitive treatment and categorised into approximate quartiles (Q1-4). The DTI quartiles were 0-14 days, 15-28 days, 29-70 days, and ≥ 71 days. Overall survival (OS) was illustrated using the Kaplan-Meier method and compared between DTI groups using Cox proportional hazards (PH) regression. RESULTS: There was no significant impact of the DTI (as quartiles) on overall CRC survival. The median length of time between DTI in this cohort was 29 days. Significant associations were identified between the DTI and self-reported ethnicity (p-value = 0.025), the site of the malignancy (colon vs rectum) (p-value < 0.0001), multidisciplinary team (MDT) review (p-value = 0.015) and the initial treatment modality (p-value < 0.0001). CONCLUSION: Prolonged DTIs did not significantly impact survival for those with CRC in the CRCSA cohort. Symptom to diagnosis time should be investigated as a determinant of survival.

Seizure Outcomes of Epilepsy Surgery in Children.

Investigators from the Hospital for Sick Children in Toronto reviewed the literature pertaining to seizure outcomes following epilepsy surgery in the pediatric population.

Impact of medical student involvement on outcomes following spine surgery: A single center analysis of 6485 patients.

Medical student (MS) observation and assistance in the operating room (OR) is a critical component of medical education. Though participation in the operating room has many benefits to the medical student, the potential cost of these experiences to the patients must be taken into account. Other studies have shown differences in outcomes with resident involvement, but the effect of medical students in the OR has been poorly understood. The objective of this study was to understand how medical students and residents impacted surgical outcomes in posterior spinal fusions, anterior cervical discectomy and fusions (ACDFs), and lumbar discectomies. We conducted a retrospective study of patients undergoing posterior spinal fusions, ACDFs, and lumbar discectomies over 15 years. There were 6485 patients met the inclusion criteria of either undergoing a posterior fusion, ACDF or lumbar discectomy (1250 posterior fusion, 1381 ACDF, 3854 lumbar discectomies). Overall, little difference was observed when a medical student was present for surgical outcomes including length of stay, infection, and readmission. For ACDFs, having a medical student present had a significantly longer procedure durations (OR = 1.612, p = 0.001) than cases without. Besides slightly longer operative time (in posterior fusions), there were no major differences in outcomes when a medical student was present in the OR.

Spatial and temporal contrasts in the distribution of crops and pastures across Amazonia: A new agricultural land use data set from census data since 1950.

Amazonia holds the largest continuous area of tropical forests with intense land use change dynamics inducing water, carbon, and energy feedbacks with regional and global impacts. Much of our knowledge of land use change in Amazonia comes from studies of the Brazilian Amazon, which accounts for two thirds of the region. Amazonia outside of Brazil has received less attention because of the difficulty of acquiring consistent data across countries. We present here an agricultural statistics database of the entire Amazonia region, with a harmonized description of crops and pastures in geospatial format, based on administrative boundary data at the municipality level. The spatial coverage includes countries within Amazonia and spans censuses and surveys from 1950 to 2012. Harmonized crop and pasture types are explored by grouping annual and perennial cropping systems, C3 and C4 photosynthetic pathways, planted and natural pastures, and main crops. Our analysis examined the spatial pattern of ratios between classes of the groups and their correlation with the agricultural extent of crops and pastures within administrative units of the Amazon, by country, and census/survey dates. Significant correlations were found between all ratios and the fraction of agricultural lands of each administrative unit, with the exception of planted to natural pastures ratio and pasture lands extent. Brazil and Peru in most cases have significant correlations for all ratios analyzed even for specific census and survey dates. Results suggested improvements, and potential applications of the database for carbon, water, climate, and land use change studies are discussed. The database presented here provides an Amazon-wide improved data set on agricultural dynamics with expanded temporal and spatial coverage. KEY POINTS: Agricultural census database covers Amazon basin municipalities from 1950 to 2012Harmonized database groups crops and pastures by cropping system, C3/C4, and main cropsWe explored correlations between groups and the extent of agricultural lands.

Identification of the Transmembrane Glucose Regulated Protein 78 as a Biomarker for the Brain Cancer Glioblastoma Multiforme by Gene Expression and Proteomic Studies.

The prognosis of patients with Glioblastoma Multiforme (GBM), the most malignant adult glial brain tumor, remains poor in spite of advances in treatment procedures, including surgical resection, irradiation and chemotherapy. Genetic heterogeneity of GBM warrants extensive studies to gain a thorough understanding of the biology of this tumor. While there have been several studies of global transcript profiling of glioma with the identification of gene signatures for diagnosis and disease management, translation into clinics is yet to happen. In the present study, we report a novel proteomic approach by using two-dimensional difference gel electrophoresis (2D-DIGE) followed by spot picking and analysis of proteins/peptides by Mass Spectrometry. We report Glucose Regulated Protein 78 (GRP78) as a differentially expressed protein in the GBM cell line compared to human normal Astrocyte cells. In addition to proteomic studies, we performed microarray analysis which further confirmed up regulation of GRP78 in GBM cells compared to human normal Astrocyte cells. GRP78 has long been recognized as a molecular chaperone in the endoplasmic reticulum (ER) and can be induced by the ER stress response. Besides its location in the ER, GRP78 has been found in cell plasma membrane, cytoplasm, mitochondria, nucleus and other cellular secretions. GRP78 is implicated in tumor cell proliferation, apoptosis resistance, immune escape, metastasis and angiogenesis, and its elevated expression usually correlates with a variety of tumor micro environmental stresses, including hypoxia, glucose deprivation, lactic acidosis and inflammatory response. GRP78 protein acts as a centrally located sensor of stress, which senses and facilitates the adaptation to the tumor microenvironment. Our findings showed differential expression of this gene in brain cancer GBM and thus confirm similarities in findings in existing transcriptional and translational studies. Thus, these findings could be of further importance for diagnostic, therapeutic and prognostic approaches for dealing with this highly malignant cancer.

Thalidomide prevents donor corneal graft neovascularization in an alkali burn model of corneal angiogenesis.

OBJECTIVE: Thalidomide is a potent inhibitor of angiogenesis. We evaluated the effects of Thalidomide on corneal angiogenesis and on tissue survival of grafts in rabbit eyes with pre-existing neovascularization secondary to alkali burn. METHODS: Sixteen rabbits received alkali burns to one cornea. One month post-injury, assessments of corneal neovascularization were performed followed by corneal transplantation. Four rabbits received oral Thalidomide and ten got placebo (powdered sugar) for thirty days. Total corneal neovascularization (NV), clock hours (CH) involved in (NV), longest (NV) pedicle length (NVP) and the duration of time required for NV to develop were assessed. RESULTS: Thalidomide significantly decreased the total neovascularization (p<0.0072), the number of (CH) involved (p<0.0002) and the longest (NVP) length (p<0.0001). There was also a significant delay in the earliest development of NV in the test group (p<0.0064). The test group retained corneal clarity significantly longer than the control group (p<0.0008). CONCLUSION: Thalidomide is an effective inhibitor of corneal angiogenesis and prolongs graft survival as measured by graft clarity in donor corneas in eyes with previous neovascularization secondary to alkali injury. CLINICAL RELEVANCE: Thalidomide may be used as a modulator of corneal angiogenesis to prolong graft survival in eyes with pre-existing corneal neovascularization.

Multiple myeloma presenting as vortex crystalline keratopathy and complicated by endocapsular hematoma.

The crystalline keratopathy of multiple myeloma may involve the corneal epithelium, but has not previously been described in a vortex epithelial distribution. Endocapsular hematomas have been described in the period immediately after extracapsular cataract extraction, but not later on or in association with systemic disease. We report a pseudophakic patient who developed a vortex epithelial crystalline keratopathy as a presenting sign of multiple myeloma, and who subsequently developed a spontaneous endocapsular hematoma.

Noncyclooxygenase metabolites of arachidonic acid amplify the vasopressin-induced Ca2+ signal in glomerular mesangial cells by releasing Ca2+ from intracellular stores.

Noncyclooxygenase metabolites of arachidonic acid may be potent modulators of the mitogenic response of renal mesangial cells to the mitogenic vasoactive peptide arginine vasopressin (AVP). Since Ca2+ is a critical second messenger in the response of mesangial cells to AVP, and Ca2+ has been implicated in the regulation of growth, we determined whether noncyclooxygenase metabolites altered the phospholipase C-Ca2+ signalling cascade which is activated by AVP. Pretreatment of mesangial cells for 10 min with lipoxygenase and cytochrome P450 monooxygenase inhibitors, nordihydroguaiaretic acid (NDGA, 10(-5) M) or SKF-525A (2.5 x 10(-5) M), but not the cyclooxygenase inhibitor indomethacin (2 x 10(-5) M), reduced the magnitude of the AVP (10(-8) and 10(-7) M)-induced increase in cytosolic free Ca2+ concentration ([Ca2+]i) without affecting inositol trisphosphate production. With 10(-8) M AVP, [Ca2+]i increased to 250 +/- 47 nM in NDGA-treated cells versus 401 +/- 59 nM in control cells (p less than 0.01). [Ca2+]i, measured 2 min after exposure to AVP, was also lower with NDGA (152 +/- 21 nM) when compared with AVP alone (220 +/- 22 nM, p less than 0.01). 14,15-epoxyeicosatrienoic acid (EET) (10(-8) M), which had no effect on inositol trisphosphate production, completely reversed the NDGA-induced inhibition of the [Ca2+]i transient, whereas 5-hydroperoxyeicosatetraenoic acid (HPETE) (5 x 10(-7) M) did not. Pretreatment with higher concentrations of 14,15-EET (10(-7)-10(-6) M) markedly potentiated the AVP-induced increase in [Ca2+]i. NDGA-induced inhibition of the AVP-generated [Ca2+]i transient was also observed when cells were incubated in low Ca2+ media ([Ca2+] less than 5 x 10(-8) M), suggesting that NDGA pretreatment impaired intracellular release of Ca2+. Since NDGA had no direct effect on inositol 1,4,5-trisphosphate-induced Ca2+ release, we postulated that NDGA blocked production of a metabolite that releases Ca2+ from intracellular stores. 14,15-EET and 15-HPETE, but not 15-hydroxyeicosatetraenoic acid (each at 3 x 10(-7) M), raised [Ca2+]i when added directly to cells in low Ca2+ media. In permeabilized cells 14,15-EET and 15-HPETE (10(-7) M) potently released Ca2+ from intracellular stores. In summary, noncyclooxygenase metabolites of arachidonic acid, and in particular P450 metabolites, are potent endogenous amplifiers of the AVP-induced [Ca2+]i signal by mechanisms not directly involving phospholipase C activation. This effect is mediated, at least in part, by enhanced release of Ca2+ from intracellular storage sites by an inositol 1,4,5-trisphosphate-independent mechanism.

Effects of tamoxifen on spinal bone density in women with breast cancer.

Bone densitometry (L2-L4) was performed on 10 postmenopausal women with breast cancer after 0, 6, and 12 months of tamoxifen treatment; the results were compared with data from 10 normal controls. The patients and controls differed significantly at 6 (P less than .05) and 12 (P less than .003) months. The tamoxifen group showed a nonsignificant mean gain in bone mineral density after 6 and 12 months of treatment (+0.024 +/- 0.014 and +0.022 +/- 0.018 g/cm2, respectively), whereas the controls showed a nonsignificant mean loss of bone mass at 6 months (-0.012 +/- 0.018 g/cm2) and a statistically significant loss of bone density after 12 months (-0.024 +/- 0.01 g/cm2). These preliminary data suggest that tamoxifen use is associated with preservation of bone mass during the first year of treatment.

Jaundice and intrahepatic cholestasis following high-dose megestrol acetate for breast cancer.

High-dose megestrol acetate, a synthetic progestin, has been advocated recently in treating patients with metastatic breast carcinoma; no significant increase in adverse effects has been reported. This report describes a patient with jaundice and intrahepatic cholestasis after high-dose megestrol acetate therapy. This cholestatic lesion may have a pathogenesis similar to that observed with estrogens and oral contraceptives.

Evaluation of metastatic melanoma with planar and SPECT scintigraphy using ZME 018 and 96.5 radiolabeled monoclonal antibodies.

To determine the feasibility of using serial injections of monoclonal antibodies (MoAbs; 96.5 and ZME 018) to evaluate metastases of malignant melanoma, 11 patients were studied. Each patient received two injections of antibody 7 days apart and were imaged 7 days after injection. Serum for human antimouse antibody (HAMA) was obtained immediately prior to injection of MoAb and 7-10 days after the second injection. Six patients were evaluated with both planar and single photon emission computed tomography (SPECT) images. Planar imaging alone was compared with SPECT alone and with planar and SPECT imaging in combination. In seven patients with 19 lesions, 96.5 and ZME 018 each identified eight lesions. In no case did one antibody identify a lesion missed by the other. In the six patients on whom SPECT imaging was performed, 14 confirmed and six suspected lesions were identified. Using planar imaging alone, only 12 confirmed and one suspected lesion were identified. HAMA titers rose significantly (0.32 optical density (O.D.) units prior to injection to 1.28 O.D. units on day 14, P less than 0.001). Allergic reactions occurred during the second injection in two patients. One of these demonstrated elevated HAMA titers and one did not. The preliminary data suggest that monoclonal antibody imaging may be aided by SPECT and that a normal HAMA titer does not preclude an allergic reaction.

Comparative effects of intravenously administered alizapride and prochlorperazine in cisplatin-induced emesis.

A randomized, double blind crossover trial compared the antiemetic effects of alizapride, a benzamide, and prochlorperazine, a phenothiazine, both administered intravenously to 32 patients treated with chemotherapy combinations containing cisplatin. The total dose of alizapride administered to each patient was 14 mg/kg, and of prochlorperazine .56 mg/kg, divided in five doses. Although alizapride resulted in complete protection against emesis in 31% of the patients during their first course of cisplatin therapy, 42% of those who received alizapride had five or more episodes of emesis. Although prochlorperazine was less effective in offering complete protection against emesis, only 15% of the patients receiving this drug vomited more than five times. The duration of emesis during prochlorperazine treatment was also significantly shorter than during alizapride therapy (p less than 0.02). Optimal dosage and pharmacokinetic distribution of both drugs should be investigated further.

Treatment effectiveness of hypnosis and behaviour therapy in smoking cessation: a methodological refinement.

Studies in smoking cessation have generally failed to adequately control for active treatment effects and have assumed that measures of smoking behaviour (i.e., estimated smoking rate, self-monitoring and chemical analysis) are equally reliable measures. Sixty smokers were randomly assigned to one of four different smoking cessation treatment groups: hypnosis, focussed smoking, attention placebo and a waiting list control. Subjects were asked to estimate and monitor their own smoking behaviour. Blood samples were also taken for thiocyanate analysis before treatment. Smoking rates were similarly measured directly, at 3 months and 6 months after treatment. The results indicate that the three measures of smoking behaviour were all highly correlated. No significant differences were found between treatments, directly after treatment or at the 3- and 6-month follow-ups. These results suggest that active treatment effects may not be responsible for behavioural change in a smoking cessation program. The implications of these findings are discussed.

Effects of dichloromethylene diphosphonate in women with breast carcinoma metastatic to the skeleton.

Ten women with skeletal metastases from breast carcinoma received dichloromethylene diphosphonate (Cl2MDP), an inhibitor of osteoclast function, in a placebo-controlled, double-blind, crossover study. Eight of these patients had either hypercalcemia or hypercalciuria, and all 10 had elevated urinary hydroxyproline levels as evidence of active skeletal disease. Eight patients had moderate to severe bone pain. After eight weeks of oral dichloromethylene diphosphonate treatment (3,200 mg per day), either preceded by or followed by an eight-week placebo period, seven of eight patients with hypercalciuria had significant reductions in urinary calcium levels, and nine of 10 had reductions in urinary hydroxyproline levels (significant in eight) when the dichloromethylene diphosphonate treatment periods were compared with prestudy or placebo periods. Additionally, seven of eight subjects had decreased pain with dichloromethylene diphosphonate. There were no adverse effects other than transient diarrhea in some patients. We conclude that oral dichloromethylene diphosphonate can significantly inhibit osteoclast-mediated bone destruction in patients with bone metastases from breast cancer.