Gastrointestinal Stromal Tumour of the Appendix: A Very Rare Entity.

A 74-year-old man who presented with upper abdominal pain was found to have an incidental appendiceal mass on cross-sectional imaging. He underwent a laparoscopic appendicectomy with histopathological examination confirming a completely resected appendiceal gastrointestinal stromal tumour (GIST). Appendiceal GISTs are rare. Therefore, there is limited evidence to guide risk stratification and management with extrapolation of prognosis from data on GISTs at other sites. This paper highlights the rarity of these tumours and presents another case which correlates well with the existing but limited literature. There is a need to maintain a registry of this rare disease entity with the maintenance of longer-term follow-up data.

Defining Benchmarks for Pelvic Exenteration Surgery: A Multicentre Analysis of Patients with Locally Advanced and Recurrent Rectal Cancer.

OBJECTIVE: To establish globally applicable benchmark outcomes for pelvic exenteration (PE) in patients with locally advanced primary (LARC) and recurrent rectal cancer (LRRC), using outcomes achieved at highly specialised centres. BACKGROUND DATA: PE is established as the standard of care for selected patients with LARC and LRRC. There are currently no available benchmarks against which surgical performance in PE can be compared for audit and quality improvement. METHODS: This international multicentre retrospective cohort study included patients undergoing PE for LARC or LRRC at 16 highly experienced centres between 2018 and 2023. Ten outcome benchmarks were established in a lower-risk subgroup. Benchmarks were defined by the 75th percentile of the results achieved at the individual centres. RESULTS: 763 patients underwent PE, of which 464 patients (61%) had LARC and 299 (39%) had LRRC. 544 patients (71%) who met predefined lower risk criteria formed the benchmark cohort. For LARC patients, the calculated benchmark threshold for major complication rate was ≤44%; comprehensive complication index (CCI): ≤30.2; 30-day mortality rate: 0%; 90-day mortality rate: ≤4.3%; R0 resection rate: ≥79%. For LRRC patients, the calculated benchmark threshold for major complication rate was ≤53%; CCI: ≤34.1; 30-day mortality rate: 0%; 90-day mortality rate: ≤6%; R0 resection rate: ≥77%. CONCLUSIONS: The reported benchmarks for PE in patients with LARC and LRRC represent the best available care for this patient group globally and can be used for rigorous assessment of surgical quality and to facilitate quality improvement initiatives at international exenteration centres.

Characterization of Ssc, an N-acetylgalactosamine-containing Staphylococcus aureus surface polysaccharide.

Whole genome sequencing has revealed that the genome of Staphylococcus aureus possesses an uncharacterized 5-gene operon (SAOUHSC_00088-00092 in strain 8325 genome) that encodes factors with functions related to polysaccharide biosynthesis and export, indicating the existence of a new extracellular polysaccharide species. We designate this locus as ssc for staphylococcal surface carbohydrate. We found that the ssc genes were weakly expressed and highly repressed by the global regulator MgrA. To characterize Ssc, Ssc was heterologously expressed in Escherichia coli and extracted by heat treatment. Ssc was also conjugated to AcrA from Campylobacter jejuni in E. coli using protein glycan coupling technology (PGCT). Analysis of the heat-extracted Ssc and the purified Ssc-AcrA glycoconjugate by tandem mass spectrometry revealed that Ssc is likely a polymer consisting of N-acetylgalactosamine. We further demonstrated that the expression of the ssc genes in S. aureus affected phage adsorption and susceptibility, suggesting that Ssc is surface-exposed. IMPORTANCE: Surface polysaccharides play crucial roles in the biology and virulence of bacterial pathogens. Staphylococcus aureus produces four major types of polysaccharides that have been well-characterized. In this study, we identified a new surface polysaccharide containing N-acetylgalactosamine (GalNAc). This marks the first report of GalNAc-containing polysaccharide in S. aureus. Our discovery lays the groundwork for further investigations into the chemical structure, surface location, and role in pathogenesis of this new polysaccharide.

Intravenous thrombolysis for multi-ethnic Asians with acute ischaemia stroke in Malaysian public primary stroke centres versus acute stroke ready hospitals: Comparison of real-world clinical outcomes.

INTRODUCTION: Intravenous thrombolysis (IVT) with recombinant tissue plasminogen activator is beneficial in acute ischaemic stroke (AIS). We aim to compare the realworld clinical outcomes and service efficiency of IVT in Malaysian primary stroke centres (PSCs) versus acute stroke ready hospitals (ASRHs). MATERIALS AND METHODS: We conducted a multi-centre cohort study involving 5 PSCs and 7 ASRHs in Malaysia. Through review of medical records of AIS patients who received IVT from 01 January 2014 to 30 June 2021, real-world data was extracted for analysis. Univariate and multivariate regression models were employed to evaluate the role of PSCs versus ASRHs in post-IVT outcomes and complications. Statistical significance was set at p<0.05. RESULTS: A total of 313 multi-ethnic Asians, namely 231 from PSCs and 82 from ASRHs, were included. Both groups were comparable in baseline demographic, clinical, and stroke characteristics. The efficiency of IVT delivery (door-toneedle time), functional outcomes (mRS at 3 months post- IVT), and rates of adverse events (intracranial haemorrhages and mortality) following IVT were comparable between the 2 groups. Notably, 46.8% and 48.8% of patients in PSCs and ASRHs group respectively (p=0.752) achieved favourable functional outcome (mRS≤1 at 3 months post-IVT). Regression analyses demonstrated that post-IVT functional outcomes and adverse events were independent of the role of PSCs or ASRHs. CONCLUSION: Our study provides real-world evidence which suggests that IVT can be equally safe, effective, and efficiently delivered in ASRHs. This may encourage the establishment of more ASRHs to extend the benefits of IVT to a greater proportion of stroke populations and enhance the regional stroke care.

Clinical-radiological features and diagnostic modalities for mediastinal melioidosis.

Melioidosis is a potentially life-threatening infection caused by the Gram-negative bacillus Burkholderia pseudomallei. Mediastinal melioidosis has a range of clinical presentations, making it difficult to diagnose: we therefore reviewed the evidence on the clinical characteristics, radiological features and invasive diagnostic modalities or interventions. An electronic search was conducted on three databases (PubMed, SCOPUS, Google Scholar) from November to December 2022. The initial search yielded 120 results, of which 34 studies met the inclusion criteria, but only 31 full-texts were retrievable. Among these, 4 were cohort studies, 26 case reports or series and 1 a conference abstract. The four main themes covered were mediastinal melioidosis as a diagnostic dilemma, unexpected complications, invasive interventions or an accompanying thoracic feature. Radiological manifestations included matting, necrosis and abscess-like collection. Severe presentations of mediastinal melioidosis included superior vena cava obstruction, sinus tract formation and pericardial tamponade. Transbronchial needle aspiration was the most common invasive diagnostic modality. Further research is needed to understand the relationship between the thoracic features of melioidosis on patient prognosis, its relationship to melioidosis transmission and potential preventive measures.

Regulation of Staphylococcal Capsule by SarZ is SigA-Dependent.

Production of capsular polysaccharides in Staphylococcus aureus is transcriptionally regulated by a control region of the cap operon that consists of SigA- and SigB-dependent promoters. A large number of regulators have been shown to affect cap gene expression. However, regulation of capsule is only partially understood. Here we found that SarZ was another regulator that activated the cap genes through the SigA-dependent promoter. Gel electrophoresis mobility shift experiments revealed that SarZ is bound to a broad region of the cap promoter including the SigA-dependent promoter but mainly the downstream region. We demonstrated that activation of cap expression by SarZ was independent of MgrA, which also activated capsule through the SigA-dependent promoter. Our results further showed that oxidative stress with hydrogen peroxide (H2O2) treatments enhanced SarZ activation of cap expression, indicating that SarZ is able to sense oxidative stress to regulate capsule production. IMPORTANCE Expression of virulence genes in Staphylococcus aureus is affected by environmental cues and is regulated by a surprisingly large number of regulators. Much is still unknown about how virulence factors are regulated by environment cues at the molecular level. Capsule is an antiphagocytic virulence factor that is highly regulated. In this study, we found SarZ was an activator of capsule and that the regulation of capsule by SarZ was affected by oxidative stress. These results provide an example of how a virulence factor could be regulated in response to an environmental cue. As the host oxidative defense system plays an important role against S. aureus, this study contributes to a better understanding of virulence gene regulation and staphylococcal pathogenesis.

Acute necrotizing encephalopathy in a child secondary to dengue fever: A case report.

Dengue fever (DF) is an important public health problem, and it is now endemic in more than 100 countries worldwide. Dengue associated neurological complication is estimated to be affecting 0.5 to 6.2% of patients. Even though this is rare, neurological manifestation of DF is an increasingly recognized entity in recent years due to significant mortality and morbidity reported/seen. Reported central nervous system manifestations due to dengue include encephalitis, encephalopathy, myelitis, myositis, acute disseminated encephalomyelitis, Guillain-Barré syndrome, stroke and etc. We report here a case of acute necrotizing encephalopathy secondary to DF in a previously healthy 12-year-old girl.

Sex-based differences in bacterial meningitis in adults: Epidemiology, clinical features, and therapeutic outcomes.

BACKGROUND: To investigate the sex-based differences in clinical features, causative pathogens, and outcomes of hospital-based culture-proven adult bacterial meningitis. OBJECTIVE: This retrospective study enrolled 621 patients at a tertiary medical center. To compare changes over time, the presentation of disease among the enrolled patients was divided into two equal time periods: the first study period (1986-2002) and the second study period (2003-2019). RESULTS: Of the 621 patients enrolled in this study, 396 were males and 225 were females. The overall case fatality rate was 30.4% with 30.1% and 31.1% in males and females, respectively. Regarding the causative pathogens, there was a rising incidence of coagulase-negative staphylococcal infections and a decreasing incidence of Klebsiella pneumoniae infection in both male and female in the second study period. The prevalence of patients with nosocomial infection in a postneurosurgical state were 41.9% (68/162) in the first study period and 58.1% (94/162) in the second study period in male group, and 34.8% (32/92) in the first study period and 65.2% (60/92) in the second study period in female group, respectively. Significant factors between the sexes difference included age (P = 0.004), traumatic brain injury (P = 0.01), alcoholism (P < 0.001), brain tumor (P < 0.001), systemic lupus erythematosus (SLE) (P = 0.004), presence of diabetic ketoacidosis/hyperglycemic hyperosmolar state (P = 0.033), brain abscess (P = 0.042), and total protein (P = 0.002) and white blood cell count (P = 0.036) of cerebrospinal fluid data. CONCLUSION: Our study revealed an increase in the number of patients with nosocomial infection with a postneurosurgical state in both male and female in the second study period. Males were younger and frequently presented with a history of head trauma and alcoholism with concomitant brain abscesses while females presented with SLE and brain tumor. The therapeutic outcome did not show differences between the sexes.

A Rat Model of Orthopedic Implant-Associated Infection for Identification of Staphylococcal Biofilm Proteins.

Secreted bacterial proteins are difficult to identify directly from an infection site due to a limited amount of bacteria and presence of a large quantity of host proteins. Here we describe a rat model of orthopedic implant that allows us to harvest bacterial biofilm materials sufficient for identification of bacterial proteins in the biofilm matrix by liquid chromatography-tandem MS (GeLC-MS/MS) analysis.

Fatal subarachnoid haemorrhage in a patient with severe dengue.

Dengue fever is one of the commonest tropical disease in the tropics. It can present with mild acute febrile illness to severe organ failure. Reported neurological complications of dengue include dengue encephalopathy, encephalitis, transverse myelitis and intracranial haemorrhage. Intracranial haemorrhage in dengue can present as subdural haematoma, extradural haematoma, intracerebral haemorrhage and subarachnoid haemorrhage. We report here a case of subarachnoid haemorrhage in a patient with severe dengue. Our patient was a 30-year-old man who presented with acute febrile illness. He subsequently developed plasma leakage and upper gastrointestinal bleeding. He then had reduced conscious level. Computed tomography of his brain showed subarachnoid haemorrhage. He eventually succumbed to his illness.

A case of Takayasu Arteritis presenting with young stroke.

Stroke is a debilitating disease as it carries significant morbidity especially when it affects the younger population. There are various etiologies of young stroke, namely arterial dissection, cardioembolism, thrombophilia, inherited genetic disorder and vasculitis. Young patient with stroke should undergo complete evaluation to identify the underlying etiology in order to prevent recurrence of stroke. Here, we would like to illustrate a case of Takayasu arteritis presenting as young stroke in a 17-years-old lady with no known medical illness.

MgrA Activates Staphylococcal Capsule via SigA-Dependent Promoter.

Staphylococcus aureus capsule polysaccharide is an important antiphagocytic virulence factor. The cap genes are regulated at the promoter element (Pcap) upstream of the cap operon. Pcap, which consists of a dominant SigB-dependent promoter and a weaker upstream SigA-dependent promoter, is activated by global regulator MgrA. How MgrA activates capsule is unclear. Here, we showed that MgrA directly bound to the Pcap region and affected the SigA-dependent promoter. Interestingly, an electrophoretic mobility shift assay showed that MgrA bound to a large region of Pcap, mainly downstream of the SigA-dependent promoter. We further showed that the ArlRS two-component system and the Agr quorum sensing system activated capsule primarily through MgrA in the early growth phases.IMPORTANCE The virulence of Staphylococcus aureus depends on the expression of various virulence factors, which is governed by a complex regulatory network. We have been using capsule as a model virulence factor to study virulence gene regulation in S. aureus MgrA is one of the regulators of capsule and has a major effect on capsule production. However, how MgrA regulates capsule genes is not understood. In this study, we were able to define the mechanism involving MgrA regulation of capsule. In addition, we also delineated the role of MgrA in capsule regulatory pathways involving the key virulence regulators Agr and Arl. This study further advances our understanding of virulence gene regulation in S. aureus, an important human pathogen.