A retrospective study of antivenom-associated adverse reaction and anaphylaxis at Ngwelezana Hospital, South Africa.

BACKGROUND: Snakebite victims are commonly seen in KwaZulu-Natal Hospitals, with only a minority of patients requiring antivenom. This study reviewed antivenom-associated adverse events at our institution, after administration of the South African Vaccine Producers (SAVP) polyvalent antivenom. METHODS: A retrospective review, over 52 months (January 2016-April 2020), of patients who received antivenom. Demographics, clinical details and clinical course following antivenom administration were analysed. RESULTS: Emergency department doctors treated 758 snakebites; 156 patients were admitted of which 51 (33%) received antivenom. Indications for antivenom included: neurotoxicity (24%), haemotoxicity (18%) and significant cytotoxicity (58%). Antivenom-associated adverse events occurred in 61% of patients; with 47% developing anaphylaxis requiring adrenaline infusion. There was a higher incidence of anaphylaxis in children (57%) than in adults (40%), p = 0.55. There was no association between antivenom dose and anaphylaxis. No benefit was noted with adrenaline premedication (p = 0.64), nor with the addition of antihistamine or steroid pre-medicants to adrenaline (p = 0.61). Multivariable logistic regression identified age as a predictor for anaphylaxis, but not dose or duration of antivenom and not any particular form of premedication. Intubation was required in 29% of patients developing anaphylaxis. There were no deaths and all patients made full recovery. CONCLUSION: Almost half of the patients at Ngwelezana hospital in Kwazulu-Natal receiving the SAVP polyvalent antivenom developed anaphylaxis requiring adrenaline infusion, with children at higher risk. The administration of this antivenom must only be given for valid indications, in a high-care environment by medical personnel ready to manage anaphylactic shock. The addition of antihistamine and corticosteroids to adrenaline for premedication has no added benefit.

Penetrating colon trauma - outcomes related to single versus multiple colonic injuries.

INTRODUCTION: There is no conclusive evidence to guide surgical management in the presence of multiple colonic injuries as opposed to a single colonic injury, and whether multiple colonic suture lines are associated with worse outcomes than single suture lines. AIM: We reviewed the outcomes of penetrating colonic trauma in relation to whether patients had single versus multiple colonic suture lines (primary repair or anastomosis) following laparotomy. METHODS: A retrospective study was conducted at a major trauma centre in South Africa from 2012-2020 for all patients over 18 years who had sustained penetrating colon injury. RESULTS: 541 cases were included: 409 with single suture line and 54 with multiple suture lines. There were no differences between groups in terms of mechanism of injury (gunshot vs stab; p = 0.328), Injury Severity Score (p = 0.071), or Penetrating Abdominal Trauma Index (p = 0.396). Admission lactate was worse for multiple suture line patients (p = 0.049), but no other blood gas parameters were different, and there was no higher incidence of damage control surgery (p = 0.558) or ICU admission (p = 0.156) for this group. There was a higher rate of diversion in the multiple suture line group (p < 0.001). Univariable logistic regression did not show an increased risk of gastro-intestinal complications, suture line leak rate, or mortality for multiple suture lines compared to single. CONCLUSION: It appears that there is no appreciable difference in outcome between patients with a single colonic suture line compared to patients with more than one suture line following trauma laparotomy. In light of this, each injury should be treated on its own merit, in the context of the patient's overall physiological condition, without undue fear of leaving the patient with more than one colonic suture line. However, judicious use of diversion remains advisable.

Penetrating colon trauma-the effect of concomitant small bowel injury on outcome.

INTRODUCTION: There is limited evidence to suggest that patients with penetrating colon injury have higher complication rates when there is concomitant small bowel (SB) injury. AIM: We performed a retrospective study looking at outcomes of penetrating colonic trauma in patients with- and without concomitant SB injury. METHODS: We interrogated our electronic registry over an eight-year period (2012-2020) for all patients over 18 years who had sustained penetrating colon injury and who had survived beyond 72 h. Demographic data, admission physiology, and Injury Severity Score (ISS) were recorded. Two groups of patients were observed: those with colonic injury (no SB injury) and those with combined colon and SB injury. Outcomes observed included leak rates, length of Intensive Care Unit (ICU) stay, length of hospital stay (LOS), morbidity and mortality. RESULTS: A total of 450 patients were eligible for analysis, of which 257 had colon injury without SB injury and 193 had a combination of colon and SB injury. There was no difference in mechanism of injury between groups. Admission physiology was similar between groups but arterial blood gas values were worse in the combined group. Rates of damage control surgery and ICU admission were higher in the combined group. Primary repair was done in equal proportions between groups but anastomosis was more frequently performed in the combined group. There was no difference in complication rates, including gastro-intestinal complications and suture line leaks. Length of ICU stay, LOS, and mortality were similar between groups. Univariable analysis demonstrated that the presence of concomitant small bowel injury was not an independent risk factor for colonic suture line failure or death. CONCLUSION: There is no evidence from this data that the presence of a combined penetrating colon and SB injury should change management priorities. Each injury should be treated on its own merit, in the context of the patient's physiology.

An audit of the outcomes of the College of Surgeons general surgery final examinations.

BACKGROUND: An audit of the Fellowship of the College of Surgeons (FCS) of South Africa examination results has not been previously performed. The purpose of this study was to review and determine any predictors of outcome (pass or fail). METHODS: The results of the FCS(SA) final examinations from October 2005 to and including October 2014, were retrieved from the College of Medicine of South Africa database. The current format of the examinations consists of two written essay question papers, an objectively structured clinical examination (OSCE), two clinical cases and two oral examinations. These were retrospectively reviewed and analysed. Predictors of failure or success were determined. RESULTS: During the 10-year study period, 472 candidates attempted the examinations. A total of 388 (82%) candidates were successful in the written component of the examination and were subsequently invited to participate in the clinical component of the examinations. Overall, 296 (63%) candidates passed and 176 (37%) failed. There were 51 candidates who were invited to the oral examinations despite an average of less than 50% in the two papers, and 34 (67%) failed the overall examination. Similarly, 126 candidates were invited having failed one of the two papers of which 81 (64%) ultimately failed. A total of 49 candidates failed the OSCE, 82% of these candidates failed overall. There were strong correlations between the averages of the papers versus the orals (Spearman ρ = 0.51), the papers versus the cases (Spearman ρ = 0.50), and the papers versus the OSCE (Spearman ρ = 0.55). CONCLUSION: The written papers are the main determinant of invitation to the second part of the examination. Candidates with marginal scores in the written component had an overall failure rate of 67%. Failing one paper and passing the other, resulted in an overall failure rate of 64%. Failing the OSCE resulted in an overall 82% failure rate. With the high failure rate of candidates with marginal scores and with the inter-examination variability of the papers, it might be prudent to revisit both the process of invitation selection and the decision to continue with the long-form of the written component.

Surgical resources in South Africa: an analysis of the inequalities between the public and private sector.

BACKGROUND: The full extent of the global burden of surgical disease is largely unknown, however, the scope of the problem is thought to be large. Despite the substantial burden of surgical disease, surgical services are inaccessible to many of those who need them most. There are disparities between public and private sectors in South Africa, which compound inequitable access to surgical care. This study forms part of a series analysing surgical resources in South Africa. METHOD: This study involved a descriptive analysis of surgical resources and included the total number of hospitals, of hospital beds, the number of surgical beds, the number of general surgeons (specialist and non-specialist), and the number of functional operating theatres in South Africa. A comparison was performed between the public and private sectors. Hospitals were contacted during the period from 1 October 2014 until 31 December 2014. RESULTS: Surgical resources were concentrated in metropolitan areas of urban provinces. There were striking differences between the public and private sectors, where private resources were comparable to those available in high income countries (HICs). CONCLUSION: Improving access to surgical services in lower middle income countries (LMICs) requires addressing gaps between the public and private sector regarding infrastructure, personnel, as well as equipment. These data identified disparities between geographic regions which may be contributing to ongoing inequity in South Africa, and by doing so allows for evidence-based planning towards improving surgical infrastructure and workforce.

A retrospective evaluation of the Modified Alvarado Score for the diagnosis of acute appendicitis in HIV-infected patients.

BACKGROUND: The aim of this study was to evaluate and compare the diagnostic value of a Modified Alvarado Score (MAS) ≥7 for acute appendicitis in both Human Immunodeficiency Virus (HIV)-negative (HIVneg) and positive (HIVpos) patientcohorts. METHODS: This retrospective study included all HIV-tested patients undergoing appendectomy at a regional hospital from March 2010 to March 2011. The MAS was calculated for all patients, as well as for the HIVneg and HIVpos groups separately. Two subgroups were considered for each of these: MAS ≥7 (high likelihood of appendicitis) and MAS <7 (low likelihood of appendicitis). These subgroups were then analysed against histopathological findings of the resected appendix. MAS specificities and sensitivities were determined by comparing Receiver Operator Characteristic (ROC) curves for the various scores. RESULTS: The study comprised 133 patients. Eighty-six (65%) were men and the median age was 20 years (range 4-64); 18 patients (14%) were HIVpos. Appendicitis was confirmed histologically in 113 patients, 100 in the HIVneg group and 13 in the HIVpos group. Specificity and sensitivity of a MAS ≥7 for HIVneg patients was 73 and 85% respectively. Based on the ROC curves, HIVpos patients only showed similar sensitivities (69%) and specificities (80%) at a MAS ≥8. CONCLUSION: A MAS ≥7 is a reliable predictor of acute appendicitis in HIVneg patients. In HIVpos patients, the MAS threshold required to accurately predict appendicitis is 8. The use of a MAS ≥7 in this group of patients will result in unnecessary surgical intervention.

Surgical resources in South Africa: an analysis of the inequalities between the public and private sector

Background:The full extent of the global burden of surgical disease is largely unknown, however, the scope of the problem is thought to be large. Despite the substantial burden of surgical disease, surgical services are inaccessible to many of those who need them most. There are disparities between public and private sectors in South Africa, which compound inequitable access to surgical care. This study forms part of a series analysing surgical resources in South Africa. Methods:This study involved a descriptive analysis of surgical resources and included the total number of hospitals, of hospital beds, the number of surgical beds, the number of general surgeons (specialist and non-specialist), and the number of functional operating theatres in South Africa. A comparison was performed between the public and private sectors. Hospitals were contacted during the period from 1 October 2014 until 31 December 2014.Results: Surgical resources were concentrated in metropolitan areas of urban provinces. There were striking differences between the public and private sectors, where private resources were comparable to those available in high income countries (HICs).Conclusion: Improving access to surgical services in lower middle income countries (LMICs) requires addressing gaps between the public and private sector regarding infrastructure, personnel, as well as equipment. These data identified disparities between geographic regions which may be contributing to ongoing inequity in South Africa, and by doing so allows for evidence-based planning towards improving surgical infrastructure and workforce

Provision of acute and elective general surgical care at a tertiary facility in the era of subspecialisation.

BACKGROUND: The need for an acute care and general surgical unit (ACGSU) to provide care for patients previously managed on an ad hoc basis by subspecialist units was recognised by the provincial government of the Western Cape Province, South Africa, the management of Groote Schuur Hospital (GSH) and the Department of Surgery. OBJECTIVE: To describe the resulting ACGSU and its functioning. METHODS: Data available from administrative records, patient files and operating room forms were collected in spreadsheet form for the period July 2013 - November 2016 inclusive. RESULTS: The ACGSU comprised a medical care team of four consultants and four to five trainees. A total of 7 571 patients were seen during the study period, the majority (66.1%) referred from the GSH Emergency Centre. Skin and soft-tissue infections formed the major disease complex. A total of 3 144 operative records were available. The most common procedures were wound debridement and inguinal hernia repairs. Trainees acted as primary surgeon in most cases. Complications (Clavien-Dindo grades I - V) were noted in 25.0% of patients. CONCLUSIONS: The ACGSU provides patient management that would otherwise complicate care in the subspecialist surgical units. It serves as a training ground for registrars and stands as a model for other institutions. Further research into the effect on patient care is planned.

Efatutazone, an oral PPAR-γ agonist, in combination with paclitaxel in anaplastic thyroid cancer: results of a multicenter phase 1 trial.

PURPOSE: A phase 1 study was initiated to determine the safety, potential effectiveness, and maximal tolerated dose and recommended phase 2 dose of efatutazone and paclitaxel in anaplastic thyroid cancer. EXPERIMENTAL DESIGN: Patients received efatutazone (0.15, 0.3, or 0.5 mg) orally twice daily and then paclitaxel every 3 weeks. Patient tolerance and outcomes were assessed, as were serum efatutazone pharmacokinetics. RESULTS: Ten of 15 patients were women. Median age was 59 years. Seven patients received 0.15 mg of efatutazone, 6 patients received 0.3 mg, and 2 patients received 0.5 mg. One patient receiving 0.3 mg of efatutazone had a partial response from day 69 to day 175; 7 patients attained stable disease. Median times to progression were 48 and 68 days in patients receiving 0.15 mg of efatutazone and 0.3 mg of efatutazone, respectively; corresponding median survival was 98 vs 138 days. The median peak efatutazone blood level was 8.6 ng/mL for 0.15-mg dosing vs 22.0 ng/mL for 0.3-mg twice daily dosing. Ten patients had grade 3 or greater adverse events (Common Terminology Criteria for Adverse Events), with 2 of these (anemia and edema) related to efatutazone. Thirteen events of edema were reported in 8 patients, with 2 of grade 3 or greater. Eight patients had ≥1 serious adverse event, with 1 of these (anemia) attributed to efatutazone and 1 (anaphylactic reaction) related to paclitaxel. The maximal tolerated dose was not achieved. Angiopoietin-like 4 was induced by efatutazone in tissue biopsy samples of 2 patients. CONCLUSIONS: Efatutazone and paclitaxel in combination were safe and tolerated and had biologic activity.

Novel high-affinity PPARgamma agonist alone and in combination with paclitaxel inhibits human anaplastic thyroid carcinoma tumor growth via p21WAF1/CIP1.

Peroxisome proliferator-activated receptor gamma (PPARgamma) agonists demonstrate antitumor activity likely through transactivating genes that regulate cell proliferation, apoptosis, and differentiation. The PAX8/PPARgamma fusion oncogene, which is common in human follicular thyroid carcinomas appears to act via dominant negative suppression of wild-type PPARgamma, suggesting that it may be a tumor suppressor gene in thyroid cells. We have identified a novel high-affinity PPARgamma agonist (RS5444) that is dependent upon PPARgamma for its biological activity. This is the first report of this molecule and its antitumor activity. In vitro, the IC50 for growth inhibition is approximately 0.8 nM while anaplastic thyroid carcinoma (ATC) tumor growth was inhibited three- to fourfold in nude mice. siRNA against PPARgamma and a pharmacological antagonist demonstrated that functional PPARgamma was required for growth inhibitory activity of RS5444. RS5444 upregulated the cell cycle kinase inhibitor, p21WAF1/CIP1. Silencing p21WAF1/CIP1 rendered cells insensitive to RS5444. RS5444 plus paclitaxel demonstrated additive antiproliferative activity in cell culture and minimal ATC tumor growth in vivo. RS5444 did not induce apoptosis but combined with paclitaxel, doubled the apoptotic index compared to that of paclitaxel. Our data indicate that functional PPARgamma is a molecular target for therapy in ATC. We demonstrated that RS5444, a thiazolidinedione (Tzd) derivative, alone or in combination with paclitaxel, may provide therapeutic benefit to patients diagnosed with ATC.

99mTc-MIBI stress-rest myocardial perfusion scintigraphy in patients with complete left bundle branch block.

BACKGROUND: Patients with complete left bundle branch block (LBBB) often show a false-positive ischaemic pattern in the interventricular septum on thallium-201 (201TI) stress-rest myocardial perfusion scintigraphy. Equivocal results have been reported with technetium-99m labelled hexakis-methoxyisobutyl isonitrile (99mTc-MIBI) in such patients. The aim of this retrospective study was to determine the effect of LBBB on the septal uptake of 99mTc-MIBI during stress-rest single photon emission computed tomography (SPECT) scintigraphy. METHODS: We studied 75 consecutive patients with LBBB, referred for 99mTc-MIBI stress-rest SPECT. Studies were evaluated by visual analysis using a semi-quantitative grading technique. In all patients with abnormal septal segments, the presence or absence of ischaemic heart disease was confirmed either clinically or by means of angiographical examination. RESULTS: Forty-three patients (57.3%) had completely normal studies. Only 15 (20%) had septal abnormalities (11 with reversible and 4 with fixed defects), while 17 patients (22.7% had abnormal segments in areas other than the interventricular septum. Except for 1 patient lost to follow-up, ischaemic heart disease was confirmed in all the patients with septal changes. CONCLUSION: We conclude that 99mTc-MIBI is more specific than 201TI for identifying ischaemic heart disease in the presence of LBBB.

Brain uptake of iodine-131 metaiodobenzylguanidine following therapy of malignant pheochromocytoma.

Intracranial metaiodobenzylguanidine (MIBG) uptake is occasionally and only faintly visualized on diagnostic studies. Recently, intense normal cerebellar uptake was described on posttherapy MIBG images. Experience at the University of Michigan with posttherapy MIBG scintigraphy of pheochromocytoma was reviewed. The patterns and correlates of intracranial uptake after therapeutic 1-131 MIBG in 25 patients (61 patient treatment encounters) were evaluated by review of records and blinded consensus interpretation of diagnostic and posttherapeutic MIBG scans. Thirty-nine (64%) patient treatment encounters demonstrated at least faint (grade 1) MIBG uptake in one or more brain sites; the most common site was the cerebellum. There was a statistically significant relation between intracranial uptake and 1) size of therapeutic dose and 2) patient age, but no relation between intracranial uptake and gender, body mass index, plasma epinephrine level, plasma norepinephrine level, urine metanephrine level, or the therapy-to-imaging interval. Although the influence of age on the pattern and intensity of intracranial uptake is unexplained, the relation to therapy dose may be explained by the possible generation of MIBG metabolites that can cross the blood-brain barrier (high activity administered and the delay until imaging). Further studies are needed to define mechanisms of intracranial uptake and relation to responses and toxicity after MIBG therapy of neuroendocrine tumors.

Randomized comparison of angioplasty of complex coronary lesions at a single center. Excimer Laser, Rotational Atherectomy, and Balloon Angioplasty Comparison (ERBAC) Study.

BACKGROUND: The purpose of this study was to test whether coronary revascularization with ablation of either excimer laser or rotational atherectomy can improve the initial angiographic and clinical outcomes compared with dilatation (balloon angioplasty) alone. METHODS AND RESULTS: At a single center, a total of 685 patients with symptomatic coronary disease warranting elective percutaneous revascularization for a complex lesion were randomly assigned to balloon angioplasty (n = 222), excimer laser angioplasty (n = 232), or rotational atherectomy (n = 231). The primary end point was procedural success (diameter stenosis < 50%, absence of death, Q-wave myocardial infarction, or coronary artery bypass surgery). The patients who underwent rotational atherectomy had a higher rate of procedural success than those who underwent excimer laser angioplasty or conventional balloon angioplasty (89% versus 77% and 80%, P = .0019), but no difference was observed in major in-hospital complications (3.2% versus 4.3% versus 3.1%, P = .71). At the 6-month follow-up, revascularization of the original target lesion was performed more frequently in the rotational atherectomy group (42.4%) and the excimer laser group (46.0%) than in the angioplasty group (31.9%, P = .013). CONCLUSIONS: Procedural success of rotational atherectomy is superior to laser angioplasty and balloon angioplasty; however, it does not result in better late outcomes. The role of plaque debulking before balloon dilatation in percutaneous coronary revascularization remains to be fully defined.

[Results after coronary bypass operation]. / Ergebnisse nach koronarer Bypass-Operation.

OBJECTIVE: To determine the influence of various risk factors on 30-day postoperative mortality rate of aortocoronary bypass operation at different centres. PATIENTS AND METHODS: Data on 227 patients (179 men, mean age 63 [40-87] years; 48 women, mean age 68 [44-81] years), 219 first operations, 8 second operations) were retrospectively analysed. In all patients the indications for aortocoronary bypass surgery had been established in the last 3 months of 1993. The operations had been performed at six cardiac centres in Germany (five in Hessen [H1-H5]) and in three hospitals elsewhere in Europe outside of Germany (E1-E3). RESULTS: The operative mortality was relatively high (5.3%), 152 patients (67%) presenting with one or more risk factors accounting for an increased perioperative mortality. The mortality rate was significantly higher for: clearly impaired left ventricular function (ejection fraction < 40%): 20 vs 3% with an ejection fraction > or = 40% (P < 0.001); emergency operation: 16.6 vs 2.7% for elective operation (P < 0.001); advanced age (> or = 70 years): 10.9 vs 3.1% for younger patients (P < 0.025); and unstable angina: 9.2 vs 2.9% with stable angina (P < 0.05). Most of the bypasses were done with the internal mammary artery (63.9%, usually combined with venous bypasses (exclusive use of venous bypasses in 35.2%), but the proportion of arterial bypasses differed greatly between centres (96% in H3, 19% in H4). CONCLUSIONS: (1) Aortocoronary bypass operations are done on many patients with important risk factors, resulting in a relatively high 30-day postoperative mortality rate. (2) The proportion of internal mammary artery bypasses markedly differs between centres in Hessen.

Imaging infection and inflammation in an African environment: comparison of 99Tcm-HMPAO-labelled leukocytes and 67Ga-citrate.

A considerable segment of the population of South Africa has a disease spectrum similar to those of the industrialized countries. However, a much larger proportion of its inhabitants comes from historically disadvantaged communities and is plagued by diseases typical of the developing world. Infectious diseases head the list as a cause of mortality in certain age groups. We have studied 108 patients presenting with a wide array of infections. Fifty-eight patients were examined with 67Ga-citrate and with 99Tcm-HMPAO-labelled leukocytes, 40 with leukocytes alone and 10 who had a high pre-test probability of tuberculosis with 67Ga only. The sensitivity and specificity of 99Tcm-labelled leukocyte scintigraphy in the 58 patients who had both studies were 89 and 84%, respectively, while the corresponding values for 67Ga scintigraphy were 81 and 74%, respectively. The overall sensitivity and specificity for 99Tcm-labelled leukocytes for detecting inflammatory sites in all 98 cases were 92 and 89%, respectively. Although labelled leukocytes were the better of the two agents for the early diagnosis of infections with a high probability of neutrophil infiltration, 67Ga remains an excellent alternative. It is the first choice in patients in whom tuberculosis or a neoplastic process is suspected as a cause of fever. It is also safer to use in areas where labelling of leukocytes is inadvisable because of inadequate sterility or where the risk is high of infecting other patients or staff with HIV.

[The recanalization of chronic coronary artery occlusions: what factors influence success?]. / Wiedereröffnung chronischer Koronararterienverschlüsse: Welche Faktoren beeinflussen den Erfolg?

Between January 1986 and June 1990, recanalization with guide-wire and balloon angioplasty (PTCA) was attempted in 509 patients (416 men, 93 women; mean age 57.5 +/- 9 years) with chronic coronary artery occlusions. The data recorded were analysed to determine the factors which influenced the outcome. The intervention was initially successful in 284 patients (55.8%; circumflex branch: 50%; right coronary artery: 52%; venous bypass graft: 50%; anterior interventricular branch: 64%). The success rate was markedly reduced if (1) the occlusion had persisted for more than 6 months (9.5%; P < 0.001); (2) occlusion had occurred at or after a vessel kink (28.5%; P < 0.001); (3) there had been no vessel "stump" (36%; P < 0.01) and (4) the occlusion was longer than 10 mm (40.7%; P < 0.05). The success-rate was higher if (1) intracoronary anastomoses were absent (61.2%); (2) occlusion had occurred in a straight vessel (62.6%); (3) there had been a vessel stump (64%); (4) the occlusion had persisted for less than 4 weeks (68.5%) and (5) the length of occlusion was < or = 10 mm (75.8%).-These data indicate that the success of PTCA after chronic coronary artery occlusion depended on the site of occlusion, its duration and length, absence of orthograde collaterals and the presence of a vessel stump. Knowing the extent of these factors helps in delineating the indications.