The effect of inhaled nitric oxide on shunt fraction in mechanically ventilated patients with COVID-19 pneumonia.

Background: Studies in patients with severe acute respiratory distress syndrome (ARDS) with refractory hypoxaemia suggest that inhaled nitric oxide (iNO) can be added to ventilatory strategies as a potential bridge to clinical improvement. However, the potential role of iNO as a management strategy in severe COVID-19 pneumonia remains unclear. The authors describe their clinical findings of using iNO for severe COVID-19 pneumonia in 10 patients with refractory hypoxaemia in a tertiary respiratory intensive care unit. The results showed an improvement in shunt fraction, P/F ratio, PaO2 and arterial oxygen saturation but the improvements did not translate into a mortality benefit. This report adds to the current body of literature indicating that the correct indications, timing, dose and duration of iNO therapy and how to harness its pleiotropic effects still remain to be elucidated. What the study adds: This brief report adds to the body of literature exploring the potential use of inhaled nitric oxide as a management strategy in patients with severe COVID-19 pneumonia with refractory hypoxaemia. What are the implications of the findings: The findings of the report shows that there is a beneficial role of using inhaled nitric oxide to improve respiratory parameters, but that it does not translate to a mortality benefit. It adds to the investigation of establishing which patients, the duration and at what dose, inhaled nitric oxide should be used to gain maximum benefit for this subgroup of patients.

Prophylaxis is the new standard of care in patients with haemophilia.

Randomised controlled clinical trial evidence on prophylaxis as optimal care for patients with haemophilia was generated more than a decade ago. However, this knowledge has not translated into clinical practice in South Africa (SA) owing to many barriers to prophylaxis. These include the high treatment burden imposed by prophylaxis (frequent injections two to four times a week), the need for intravenous access to administer replacement clotting factor therapies, and the higher volume of clotting factor required compared with episodic treatment. The recently introduced non-factor therapies in haemophilia care have addressed many of these barriers. For example, emicizumab, which is currently the only globally approved non-factor therapy, can be administered subcutaneously less frequently (weekly, fortnightly or every 4 weeks) and has led to global adoption of prophylaxis as the standard of care in haemophilia by the bleeding disorders community. Haemophilia A is the most prevalent clotting factor deficiency in SA, with >2 000 people diagnosed to date. However, only a few of these patients are currently on prophylaxis. In this 'In Practice' article, we review the rationale for prophylaxis, outline its goals and benefits, and provide evidence-based guidance on which haemophilia patients should be prioritised for emicizumab prophylaxis. This consensus guidance facilitates the adoption of prophylaxis as a national policy and the new standard of care in haemophilia in SA.

The Association of Clinical Characteristics and Tumour Markers With Image-Defined Risk Factors in the Management of Neuroblastoma in South Africa.

AIMS: Image-defined risk factors (IDRFs) in neuroblastoma predict surgical complications and management outcomes. As there is a lack of data regarding the association of IDRFs with clinical and pathological factors, this study evaluated the prognostic value of IDRFs to predict neuroblastoma survival outcomes. MATERIALS AND METHODS: This was a retrospective study including 345 patients and reviewed diagnostic imaging for 20 IDRFs, pleural effusions and ascites. The IDRFs were grouped into five 'primary IDRFs' cohorts with vascular encasement, involvement of multiple body compartments, organ infiltration, airway obstruction and intraspinal extension. The association between clinical, histopathological and biological characteristics of neuroblastoma and management was evaluated. RESULTS: More patients without IDRFs had operations compared with patients with IDRFs, with a trend towards significance (64.4% versus 35.6%, P = 0.082). Patients with multiple compartment tumour involvement (P = 0.003) and organ infiltration (P < 0.001) had a higher risk of surgical complications. The 5-year overall survival of the group with more than one IDRF was 0.0% and those with pleural effusions or ascites 6.7%, associated with the worst outcome (P = 0.005). The total number of IDRFs was not predictive of the metastatic remission rate (P = 0.585) or overall survival (P = 0.142), with no conclusive association found between IDRF groups and clinical or biological markers. CONCLUSIONS: Patients with more than one IDRF had the shortest survival time, whereas those with pleural effusions and ascites at diagnosis had a poor outcome. Standardised reporting of IDRFs is crucial for predicting prognosis.

Assessment of the anterior loop of the inferior alveolar nerve using reformatted computed tomography: a retrospective study.

The anterior loop of the inferior alveolar nerve (IAN) is an important landmark in the anterior mandible that must be considered during the placement of dental implants. We measured the length and prevalence of loops of the IAN in 188 consecutive, dentate patients using reformatted computed tomography (CT). A total of 158/188 (84%) had at least one anterior loop; 111/188 (59%) had bilateral loops. The mean (SD) length of the loops in the third quadrant was 1.4 (0.7)mm; 95% CI 1.3 to 1.6; (range 0.3 - 4.0mm). The mean (SD) length of the loops in the fourth quadrant was 1.5 (0.9)mm; 95% CI 1.4 to 1.6; range 0.3 - 5.5mm. In total 42/188 (22%) had loops that were longer than 2mm in quadrants three and four. CT images that have been reformatted with specialised software may be useful to identify loops in the IAN, particularly when recent cone-beam CT images are not freely available. The prevalence of these loops is high while their length varies, which makes meticulous assessment necessary before the placement of implants.

Episodic replacement of clotting factor concentrates does not prevent bleeding or musculoskeletal damage - the MUSFIH study.

PATIENTS AND METHODS: A longitudinal study was carried out in 255 children from 10 centres in nine developing countries over 5 years to assess the musculoskeletal outcome of children on episodic factor replacement. Outcome was documented by assessment of the annual joint bleeding rate (AJBR), WFH clinical and Pettersson radiological joint scores as well as the FISH score for activities. Of the 203 patients for whom data was available at the end of 5 years, 164 who had received only episodic treatment are included in this report. RESULTS: The median age at the beginning of the study was 10 years (IQR 7-12). The median clotting factor concentrate (CFC) usage was 662 IU kg-1 year-1 (IQ range: 280-1437). The median AJBR was 10 (IQ range: 5-17). The median AJBR was higher in the older children with the median being 5 for the 5 year old child, while it was 9 for the 10 year old and 11 for children older than 15. Given the episodic nature of the replacement therapy, those with a higher AJBR used significantly greater annual CFC doses (P < 0.001); The median change in WFH clinical score and Pettersson radiological score over the 5 years was 0.4/year for each, while the FISH deteriorated at a rate of 0.2/year with poor correlation of these changes with CFC dose. WFH and FISH scores were significantly worse in those with an AJBR of >3 per year (P = 0.001). The change in the Pettersson score was significantly more in those with an AJBR of >5 per year (P = 0.020). Significant changes in FISH scores were only noted after 10 years of age. CONCLUSION: Episodic CFC replacement over a large range of doses does not alter the natural course of bleeding in haemophilia or the musculoskeletal deterioration and should not be recommended as a long term option for treatment. Prophylaxis is the only way to preserve musculoskeletal function in haemophilia.

Bioreactor microbial ecosystems for thiocyanate and cyanide degradation unravelled with genome-resolved metagenomics.

Gold ore processing uses cyanide (CN(-) ), which often results in large volumes of thiocyanate- (SCN(-) ) contaminated wastewater requiring treatment. Microbial communities can degrade SCN(-) and CN(-) , but little is known about their membership and metabolic potential. Microbial-based remediation strategies will benefit from an ecological understanding of organisms involved in the breakdown of SCN(-) and CN(-) into sulfur, carbon and nitrogen compounds. We performed metagenomic analysis of samples from two laboratory-scale bioreactors used to study SCN(-) and CN(-) degradation. Community analysis revealed the dominance of Thiobacillus spp., whose genomes harbour a previously unreported operon for SCN(-) degradation. Genome-based metabolic predictions suggest that a large portion of each bioreactor community is autotrophic, relying not on molasses in reactor feed but using energy gained from oxidation of sulfur compounds produced during SCN(-) degradation. Heterotrophs, including a bacterium from a previously uncharacterized phylum, compose a smaller portion of the reactor community. Predation by phage and eukaryotes is predicted to affect community dynamics. Genes for ammonium oxidation and denitrification were detected, indicating the potential for nitrogen removal, as required for complete remediation of wastewater. These findings suggest optimization strategies for reactor design, such as improved aerobic/anaerobic partitioning and elimination of organic carbon from reactor feed.

Nephroblastoma--a 25-year review of a South African unit.

RATIONALE: To determine the outcome of patients with nephroblastoma in a South African hospital. OBJECTIVE: To determine if there is a difference in the outcome of patients with nephroblastoma comparing two treatment protocols SIOP (Société International D'Oncologie Pédiatrique Protocol) versus NWTS (National Wilms' Tumour Study Protocol). METHODS AND RESULTS: A retrospective audit of 25 years (1983-2007), of children diagnosed with nephroblastoma in Tygerberg Hospital. One hundred and seven patients were included in the study and 98 were analyzed. The average age at diagnosis was 3.8 years. Most patients (37%) presented with stage 1 of the disease, followed by patients with stage 3 (27%). Most patients were treated according to the SIOP protocol (61%). Gender and race did not influence the outcome. Patients with stage 1 and 2 of the disease had the best outcome (76% versus 43% for stages 3 and 4). The SIOP group had a better outcome than the NWTS group (p value 0.001). The two groups had an equal distribution of the stage of presentation. The tumor volumes were bigger in the NWTS group (1004cm3 compared to 613cm3). Nutritional status did not influence the outcome although more patients were underweight for age in the SIOP group. The statistical methods used were: Kaplan Meier, Gehan's Wilcoxon Test, Chi -square test and the Fisher exact test. DISCUSSION: Contrary to the other studies, patients treated according to the SIOP protocol had a statistically significant better outcome. Larger collaborative studies are needed to investigate this result in Africa.

Substance abuse among oral healthcare workers.

The abuse of both licit and illicit substances by the general population affects at least one in ten people. Research shows that the oral healthcare worker has at least the same prevalence of substance abuse, perhaps even higher. The emergence of prescription drug abuse is one of the most worrying and dangerous aspects for the healthcare worker, due to ease of access to such drugs. According to the United Nations, prescription drug abuse is amongst the top three practices of substance abuse. We have an obligation to incorporate the evidence of substance abuse among oral healthcare professionals in our undergraduate dental curricula in order to combat this phenomenon. As the stress of daily survival in single practitioner practices increase, so will the danger of substance abuse. This may lead to impairment of the healthcare worker and ultimately loss of registration. It will take a combined effort from organised dentistry and academic institutions to establish a national strategy to ensure we address this important issue at undergraduate level and provide support at practitioner level. This paper will deal with substance abuse and the implications of impairment it holds for the oral healthcare worker.

Substance abuse and oral health: an overview.

Substance abuse is a worldwide phenomenon. It is on the increase in most countries and claims the lives of millions every year. Substance abuse may involve licit and illicit drugs, with licit substances claiming more lives than illicit drugs. Illicit substance abuse is on the increase, especially with new drugs emerging on the world market every year. These new drugs appear faster than scientific studies can keep pace in determining their possible detrimental influences on health. Many abused drugs do have oral health complications. For this reason, it is important for dentists to have a thorough knowledge of the oral environment to be able to detect any abnormalities, regardless of what the underlying cause may be. Due to the nature of illicit substance abuse, reliable information and science is hard to come by. This overview will focus on the direct consequences for oral health, whilst acknowledging that substance abuse may also have direct and indirect influences on general health.

Enhanced activity of demineralised bone matrix augmented with xenogeneic bone morphogenetic protein complex in rats.

INTRODUCTION: Demineralised bone matrix (DBM) is an allograft material widely used as a bone filler and bone graft substitute. DBM contains bone morphogenetic proteins (BMPs), which induce and regulate bone formation during embryogenesis and in postnatal life. AIMS AND OBJECTIVES: To investigate the osteoinductivity of DBM augmented with xenogeneic BMP-complex at different doses. MATERIALS AND METHODS: Rat DBM was augmented with BMP-complex purified from porcine diaphyseal bone. RESULTS: Dorsal subcutaneous implantation of 25 mg rat allogeneic DBM augmented with 0, 3, 6 and 12 mg BMP-complex per gram of DBM resulted in dose dependant up-regulation of bone formation on day 21, as scored histologically and biochemically. CONCLUSIONS: Allogeneic DBM can be augmented with xenogeneically sourced BMP-complex to improve DBM performance in vivo. This work demonstrates the potential of BMP-complex augmented DBM to induce new bone formation with improved parameters of bone formation.

Epidemiology of oral squamous cell carcinoma.

The National Cancer Registry (NCR) of South Africa publishes the pathology-based cancer incidence in the country and is the main cancer data source. The data published by the NCR have been used extensively in the development of the draft national guidelines for cancer prevention and control as well as for cancer research. The list of contributing pathology laboratories is fairly inclusive. Data from the NCR and the University of Limpopo, Department of Oral Pathology for the five years 1997-2001 were combined and then filtered for sites in the oral and oropharyngeal region. Age-Standardised Incidence Rates (ASIR) and the Cumulative Lifetime Risk (LR) for males and females in the different population groups were determined. Comprehensive reporting of oral and oropharyngeal cancer incidence will influence the allocation of government resources for prevention and treatment of oral cancers.

Aetiology of oral cancer.

The terms Oral cancer (OC) and oral squamous cell carcinoma (OSCC) are used interchangeably, as more than 95% of all OCs are OSCCs. Worldwide up to 275 000 new cases of OC are seen every year. Most of these cases are seen in developing countries such as South Africa. Up to 50% of all patients living with OC will die within five years, and this survival rate has not improved over the last few decades. Tobacco and alcohol usage account for up to 75% of all OC cases. As these causative factors can be avoided, all oral health workers should be aware of the aetiology of OC so that sound preventive advice may be given to their patients. Infections and nutrition play a lesser but still important role in the aetiology of OC. This article reviews the importance of the aetiology of OC, with the emphasis on tobacco and alcohol.

Chronic ulcerative stomatitis: a distinct clinical entity?

Chronic ulcerative stomatitis (CUS) is a mucocutaneous disorder which is characterised by persistent oral mucosal ulceration. The clinical appearance is often reminiscent of oral lichen planus (OLP) leading to erroneous diagnoses. The immune mediated inhibition of the CUS protein (CUSP) is implicated in the pathogenesis of CUS. CUSP acts as an anti-apoptotic protein and when its action is prevented it may result in significant epithelial injury. The objective or this article is to present the first documented case of CUS in South Africa, with relevant reference to current international literature. CUS should be considered in patients previously diagnosed with OLP but who are unresponsive to glucocorticosteroid therapy. The condition can be successfully managed using hydroxychloroquine.