Expression of sterile-α and armadillo motif containing protein (SARM) in rheumatoid arthritis monocytes correlates with TLR2-induced IL-1ß and disease activity.

OBJECTIVE: Cartilage and bone damage in RA are associated with elevated IL-1ß. The effects of IL-1ß can be reduced by biological therapies that target IL-1ß or TNF-α. However, the mechanisms responsible for increased IL-1ß and the effect of anti-TNF-α have not been fully elucidated. Recently, sterile-α and armadillo motif containing protein (SARM) was identified as a negative regulator of toll-like receptor (TLR) induced IL-1ß secretion through an interaction with the inflammasome. This study set out to investigate SARM during TLR-induced IL-1ß secretion in RA peripheral blood monocytes and in patients commencing anti-TNF-α treatment. METHODS: Monocytes were isolated from RA patients and healthy controls; disease activity was measured by DAS28. IL-1ß secretion was measured by ELISA following TLR1/2, TLR4 and TLR7/8 stimulation. The mRNA expression of SARM1, IL-1ß and the components of the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome were measured by quantitative PCR. SARM protein expression was measured by western blotting. RESULTS: TLR1/2 activation induced elevated IL-1ß in RA monocytes compared with healthy controls (P = 0.0009), which negatively correlated with SARM1 expression (P = 0.0086). Lower SARM expression also correlated with higher disease activity (P = 0.0246). Additionally, patients responding to anti-TNF-α treatment demonstrated a rapid upregulation of SARM, which was not observed in non-responders. CONCLUSION: Together, these data highlight a potential contribution from SARM to RA pathophysiology where decreased SARM may lead to elevated IL-1ß associated with RA pathogenesis. Furthermore, the data additionally present a potential mechanism by which TNF-α blockade can modify IL-1ß secretion.

Analyses of the performance of the Ebola virus disease alert management system in South Sudan: August 2018 to November 2019.

South Sudan implemented Ebola virus disease preparedness interventions aiming at preventing and rapidly containing any importation of the virus from the Democratic Republic of Congo starting from August 2018. One of these interventions was a surveillance system which included an Ebola alert management system. This study analyzed the performance of this system. A descriptive cross-sectional study of the Ebola virus disease alerts which were reported in South Sudan from August 2018 to November 2019 was conducted using both quantitative and qualitative methods. As of 30 November 2019, a total of 107 alerts had been detected in the country out of which 51 (47.7%) met the case definition and were investigated with blood samples collected for laboratory confirmation. Most (81%) of the investigated alerts were South Sudanese nationals. The alerts were identified by health workers (53.1%) at health facilities, at the community (20.4%) and by screeners at the points of entry (12.2%). Most of the investigated alerts were detected from the high-risk states of Gbudwe (46.9%), Jubek (16.3%) and Torit (10.2%). The investigated alerts commonly presented with fever, bleeding, headache and vomiting. The median timeliness for deployment of Rapid Response Team was less than one day and significantly different between the 6-month time periods (K-W = 7.7567; df = 2; p = 0.0024) from 2018 to 2019. Strengths of the alert management system included existence of a dedicated national alert hotline, case definition for alerts and rapid response teams while the weaknesses were occasional inability to access the alert toll-free hotline and lack of transport for deployment of the rapid response teams which often constrain quick response. This study demonstrates that the Ebola virus disease alert management system in South Sudan was fully functional despite the associated challenges and provides evidence to further improve Ebola preparedness in the country.

What did we learn from preparing for cross-border transmission of Ebola virus disease into a complex humanitarian setting - The Republic of South Sudan?

BACKGROUND: Following the West Africa Ebola virus disease (EVD) outbreak (2013-2016), WHO developed a preparedness checklist for its member states. This checklist is currently being applied for the first time on a large and systematic scale to prepare for the cross border importation of the ongoing EVD outbreak in the Democratic Republic of Congo hence the need to document the lessons learnt from this experience. This is more pertinent considering the complex humanitarian context and weak health system under which some of the countries such as the Republic of South Sudan are implementing their EVD preparedness interventions. MAIN TEXT: We identified four main lessons from the ongoing EVD preparedness efforts in the Republic South Sudan. First, EVD preparedness is possible in complex humanitarian settings such as the Republic of South Sudan by using a longer-term health system strengthening approach. Second, the Republic of South Sudan is at risk of both domestic and cross border transmission of EVD and several other infectious disease outbreaks hence the need for an integrated and sustainable approach to outbreak preparedness in the country. Third, a phased and well-prioritized approach is required for EVD preparedness in complex humanitarian settings given the costs associated with preparedness and the difficulties in the accurate prediction of outbreaks in such settings. Fourth, EVD preparedness in complex humanitarian settings is a massive undertaking that requires effective and decentralized coordination. CONCLUSION: Despite a very challenging context, the Republic of South Sudan made significant progress in its EVD preparedness drive demonstrating that it is possible to rapidly scale up preparedness efforts in complex humanitarian contexts if appropriate and context-specific approaches are used. Further research, systematic reviews and evaluation of the ongoing preparedness efforts are required to ensure comprehensive documentation and application of the lessons learnt for future EVD outbreak preparedness and response efforts.

Anesthesia Provision in Disasters and Armed Conflicts.

PURPOSE OF REVIEW: Disasters and armed conflicts are characterized by high numbers of trauma cases, and occur mainly in developing countries where the healthcare response is already impaired, resulting in an inadequate response. Aside of the trauma cases, other surgical health conditions are also still present and require urgent care. Surgical care needs are different from context to context and depend on local means and capabilities. RECENT FINDINGS: Doctors without Borders (MSF) has proven that even in precarious situations, safe administration of anesthesia is possible, and the "do no harm" principle can and must be upheld. Anesthesia providers need to recognize the difficulties linked to these contexts. SUMMARY: Local, spinal and general intravenous (mainly with Ketamine) anesthetics seem to be the most widely accepted. Inhalation anesthesia has constraints; regional is underused and epidural is not recommended. Standard operative procedures should be in place, and an informed consent from the patient must be granted.

"Providing a Roof" and More to Communities Affected by Typhoon Haiyan in the Philippines: the Médecins Sans Frontières Experience.

OBJECTIVES: Typhoon Haiyan hit the Philippines in November 2013 and left a trail of destruction. As part of its emergency response, Médecins Sans Frontières distributed materials for reconstructing houses and boats as standardized kits to be shared between households. Community engagement was sought and communities were empowered in deciding how to make the distributions. We aimed to answer, Was this effective and what lessons were learned? METHODS: A cross-sectional survey using a semi-structured questionnaire was conducted in May 2014 and included all community leaders and 269 households in 22 barangays (community administrative areas). RESULTS: All houses were affected by the typhoon, of which 182 (68%) were totally damaged. All households reported having received and used the housing material. However, in 238 (88%) house repair was incomplete because the materials provided were insufficient or inappropriate for the required repairs. CONCLUSION: This experience of emergency mass distribution of reconstruction or repair materials of houses and boats led by the local community was encouraging. The use of "standardized kits" resulted in equity issues, because households were subjected to variable degrees of damage. A possible way out is to follow up the emergency distribution with a needs assessment and a tailored distribution. (Disaster Med Public Health Preparedness. 2017;11:285-289).

Descriptive spatial analysis of the cholera epidemic 2008-2009 in Harare, Zimbabwe: a secondary data analysis.

This ecological study describes the cholera epidemic in Harare during 2008-2009 and identifies patterns that may explain transmission. Rates ratios of cholera cases by suburb were calculated by a univariate regression Poisson model and then, through an Empirical Bayes modelling, smoothed rate ratios were estimated and represented geographically. Mbare and southwest suburbs of Harare presented higher rate ratios. Suburbs attack rates ranged from 1.2 (95% Cl = 0.7-1.6) cases per 1000 people in Tynwald to 90.3 (95% Cl = 82.8-98.2) in Hopley. The identification of this spatial pattern in the spread, characterised by low risk in low density residential housing, and a higher risk in high density south west suburbs and Mbare, could be used to advocate for improving water and sanitation conditions and specific preparedness measures in the most affected areas.

An elderly woman with 'Red Man Syndrome' in association with oral vancomycin therapy: a case report.

INTRODUCTION: 'Red Man Syndrome' is a recognized adverse reaction to intravenous vancomycin therapy. This case concerns an elderly woman who developed a 'Red Man Syndrome' reaction whilst on oral vancomycin therapy for Clostridium difficile (C difficile) diarrhoea. Isolated case reports exist recording this reaction in association with oral vancomycin therapy in patients with inflammatory bowel conditions or impaired renal function, of which this patient had both. CASE PRESENTATION: An 82 year old Caucasian woman who developed C. difficile diarrhoea after co-amoxiclav therapy for a urinary tract infection. She was treated with oral vancomycin therapy during which she developed a widespread erythematous rash in keeping with that of 'Red Man Syndrome'. This rash resolved on stopping the oral vancomycin. CONCLUSION: This case is important in the light of the increasing use of oral vancomycin to treat C. difficile diarrhoea, a rising problem in the UK. It also calls us to review our understanding of the mechanism of the 'Red Man Syndrome' reaction. It is possible that significant absorption of orally administered vancomycin occurs in the presence of an inflammatory bowel condition.

How many sentinel nodes should be harvested in oral squamous cell carcinoma?

The number of harvested lymph nodes when performing sentinel lymph node (SLN) biopsy remains controversial. The aim of this study was to examine the maximum number of nodes to be harvested for histopathological analysis. We also wanted to determine if the level of radioactivity within a SLN or its size were indicators for the likelihood of nodal metastases. The SLNs from 34 neck dissection specimens from patients with T1/T2 N0 oral and oropharyngeal carcinomas were included. Altogether 76 SLNs were measured for radioactivity and lymph node dimensions and volume. Tumour was identified in 16 of 76 nodes (positive nodes), and the remaining 60 nodes were free from tumour (negative nodes). In 9 of 16 cases, metastases were in the hottest node. Two patients had more than one positive SLN: the first and fourth hottest in one and the second and fourth hottest nodes in another contained tumour. However, all patients would have been staged accurately if only the hottest three sentinel nodes had been retrieved. Lymph nodes that contained tumour had a greater maximum diameter than non-metastatic SLNs. To stage the neck accurately, only the three hottest lymph nodes required sampling.

Preliminary experience of 99mTc-Aprotinin scintigraphy in amyloidosis.

BACKGROUND AND AIM: Radio-labelled Aprotinin has been shown to bind with amyloid fibrils in vitro as well as in vivo. The aim was to test the usefulness of 99mTc-Aprotinin imaging in systemic amyloidosis. METHODS: Thirty-five cases who had 99mTc-Aprotinin scans for the assessment of systemic amyloidosis were reviewed retrospectively. Eighteen had biopsy-proven amyloidosis and 17 were controls (amyloidosis was excluded by negative biopsies and non-invasive tests). Five of 18 patients with amyloidosis had final diagnosis of cardiac amyloid. RESULTS: Physiological uptake of 99mTc-Aprotinin was noted in the urinary tract (kidneys and bladder) and in the liver of all patients and controls; and non-specific uptake of 99mTc-Aprotinin was visualised in the spleen and oro-facial structures in the majority of both groups. Myocardial 99mTc-Aprotinin uptake was noted in all five patients with final diagnosis of cardiac amyloidosis and in none of the 30 subjects who did not have cardiac amyloid. The median heart to background uptake ratio was 2.0 in cardiac amyloid patients and 1.1 in subjects without cardiac amyloid (P = 0.0004). Single Photon Emission Tomography (SPECT) studies of the thorax confirmed that the site of uptake lay within the myocardium. In the amyloidosis group, site-specific 99mTc-Aprotinin uptake was also identified in the subcutaneous tissue of the legs and in a breast nodule shown to be positive for amyloidosis on biopsy. CONCLUSIONS: 99mTc-Aprotinin imaging may be a useful non-invasive method for the assessment of the presence and extent of extra-abdominal amyloid, particularly cardiac amyloidosis. It has little role in diagnosis of amyloidosis involving the oro-facial and abdominal structures.

The use of sentinel node biopsy to upstage the clinically N0 neck in head and neck cancer.

OBJECTIVE: To investigate the possible role of sentinel node biopsy (SNB) alone to upstage the clinically N0 neck in patients with oral and oropharyngeal squamous cell carcinoma. DESIGN: Prospective clinical study. SETTING: Head and neck referral center. PATIENTS: Patients with primary untreated oral and/or oropharyngeal squamous cell carcinoma accessible to injection and with clinically N0 necks were enrolled in the study. INTERVENTION: An SNB was performed after radiocolloid and blue dye injection. Preoperative lymphoscintigraphy and the perioperative use of a gamma probe identified radioactive sentinel nodes and visualization of blue-stained lymphatics identified blue sentinel nodes. If the sentinel node was found negative, there was no further treatment to the neck. If the sentinel node tested positive, a therapeutic neck dissection was performed. All patients underwent regular follow-up at the outpatient clinic to identify possible recurrence. MAIN OUTCOME MEASURES: Upstaging of the clinically N0 neck by SNB and development of subsequent disease in SNB-negative necks. RESULTS: An SNB was performed on 57 clinically N0 necks in 48 patients. Sentinel nodes were harvested in 43 (90%) of 48 patients. Fifteen (35%) of 43 patients were upstaged by SNB and 28 (65%) of 43 were staged SNB negative. There was a mean follow-up of 18 months. One patient developed subsequent disease after having been staged negative with SNB. The overall sensitivity of the procedure using the full pathologic protocol was 94% (15/16). CONCLUSIONS: Sentinel node biopsy can be used to upstage the N0 neck in patients with early subclinical nodal disease. However, before it becomes the standard of care in head and neck squamous cell carcinoma, longer follow-up observational trials are needed.

The natural history of venous thromboembolism: impact on ventilation/perfusion scan reporting.

Deep vein thrombosis (DVT) and pulmonary embolism (PE) are separate but related aspects of the same dynamic disease process known as venous thromboembolism (VTE). Recent community studies have shown that VTE is a major health issue for the developed world, with at least 201,000 new cases each year in the United States, comprising 107,000 with DVT and 94,000 with PE. A quarter of PE cases die within 7 days, some so rapidly that treatment or intervention is impossible. Despite the availability of heparin prophylaxis, the annual incidence of VTE has remained constant at 1 event per 1,000 person-years since 1979 but reaches 1 event per 100 person-years for the over-85-year-olds. The most important risk factors for VTE are hemostatic and environmental. The recent discoveries of factor V Leiden, prothrombin 20210A, and high concentrations of factor VIII have highlighted the increasing importance of a genetic predisposition to thrombophilia. Acquired hemostatic factors include pregnancy and the puerperium, oral contraception, hormone-replacement therapy, malignant tumors, and antiphospholipid syndromes. Important environmental risk factors include hospitalization with previous surgery or trauma, confinement in a care facility, neurologic disease or paraplegia after stroke, current or recent central venous catheter or transvenous pacemaker, and long airplane flights. Internists may be confused about the risk of PE after ventilation/perfusion (VQ) imaging. This may well arise from their use of the relative risk of PE after a low-probability category scan rather than the absolute risk obtained by incorporating the PE prevalence for their particular patient in the risk analysis. Ideally, personal communication with an experienced referring physician provides this clinical information for nuclear medicine. Diagnostic tools or checklists can be used as an alternative. A general knowledge of the natural history of VTE will encourage the nuclear medicine physician to provide an appropriate clinical signal to complement VQ categorical analysis. Combination of these 2 dynamic elements of the art and science of VQ scan reporting-the clinical pretest probability of PE and lung scan category-will permit an accurate prediction of the absolute risk of PE posttest.

Anatomy of the human body

The term human anatomy comprises a consideration of the various structures which make up the human body. In a restricted sense it deals merely with the parts which form the fully developed individual and which can be rendered evident to the naked eye by various methods of dissection. Regarded from such a standpoint it may be studied by two methods: (1) the various structures may be separately considered - systemic anatomy; or (2) the organs and tissues may be studied in relation to one another - topographical or regional anatomy (AU)