Study protocol: infectious diseases consortium (I3D) for study on integrated and innovative approaches for management of respiratory infections: respiratory infections research and outcome study (RESPIRO).

BACKGROUND: Community-acquired respiratory infections are a leading cause of illness and death globally. The aetiologies of community-acquired pneumonia remain poorly defined. The RESPIRO study is an ongoing prospective observational cohort study aimed at developing pragmatic logistical and analytic platforms to accurately identify the causes of moderate-to-severe community-acquired pneumonia in adults and understand the factors influencing disease caused by individual pathogens. The study is currently underway in Singapore and has plans for expansion into the broader region. METHODS: RESPIRO is being conducted at three major tertiary hospitals in Singapore. Adults hospitalised with acute community-acquired pneumonia or lower respiratory tract infections, based on established clinical, laboratory and radiological criteria, will be recruited. Over the course of the illness, clinical data and biological samples will be collected longitudinally and stored in a biorepository for future analysis. DISCUSSION: The RESPIRO study is designed to be hypothesis generating, complementary to and easily integrated with other research projects and clinical trials. The detailed clinical database and biorepository will yield insights into the epidemiology and outcomes of community-acquired lower respiratory tract infections in Singapore and the surrounding region and offers the opportunity to deeply characterise the microbiology and immunopathology of community-acquired pneumonia.

Is there an optimal timing between radiotherapy and surgery to reduce wound complications in metastatic spine disease? A systematic review.

PURPOSE: Surgery with radiation therapy (RT) is more effective in treating spinal metastases, than RT alone. However, RT when administered in close proximity to surgery may predispose to wound complications. There exist limited guidelines on the optimal timing between RT and surgery. The purpose of this systematic review is to: (1) address whether pre-operative RT (preop-RT) and/or post-operative RT (postop-RT) is associated with wound complications and (2) define the safe interval between RT and surgery or vice versa. METHODS: PubMed, Embase and Scopus databases were systematically searched for articles dealing with spinal metastases, treated with surgery and RT, and discussing wound status. RESULTS: We obtained 2332 articles from all databases, and after applying exclusion criteria, removing duplicates and reading the full text, we identified 27 relevant articles. Fourteen additional articles were identified by hand-search, leading to a total of 41 articles. All 41 mentioned wound complications/healing. Sixteen articles discussed preop-RT, 8 postop-RT, 15 both, and 2 mentioned intraoperative-RT with additional pre/postop-RT. Twenty studies mentioned surgery-RT time interval; one concluded that wound complications were higher when RT-surgery interval was ≤ 7 days. Seven studies reported significant association between preop-RT and wound complications. CONCLUSIONS: Evidence is insufficient to draw definitive conclusion about optimal RT-surgery interval. However, based on published literature and expert opinions, we conclude that an interval of 2 weeks, the minimum being 7 days, is optimum between RT-surgery or vice versa; this can be reduced further by postop-stereotactic body RT. If RT-surgery window is > 12 months, wound-complications rise. Postop-RT has fewer wound complications versus preop-RT.

Advancing biomarker development for diagnostics and therapeutics using solid tumour cancer stem cell models.

The cancer stem cell model hopes to explain solid tumour carcinogenesis, tumour progression and treatment failure in cancers. However, the cancer stem cell model has led to minimal clinical translation to cancer stem cell biomarkers and targeted therapies in solid tumours. Many reasons underlie the challenges, one being the imperfect understanding of the cancer stem cell model. This review hopes to spur further research into clinically translatable cancer stem cell biomarkers through first defining cancer stem cells and their associated models. With a better understanding of these models there would be a development of more accurate biomarkers. Making the clinical translation of biomarkers into diagnostic tools and therapeutic agents more feasible.

Complements and Their Role in Systemic Disorders.

The complement system is critical to the body's innate defense against exogenous pathogens and clearance of endogenous waste, comprising the classical, alternative, and lectin pathways. Although tightly regulated, various congenital and acquired diseases can perturb the complement system, resulting in specific complement deficiencies. Systemic rheumatic, neurological, ophthalmological, renal, and hematological disorders are some prototypical complement-mediated diseases. An adequate understanding of the mechanisms of the normal complement system and the pathophysiology of complement dysregulation is critical for providing diagnostic clues and appropriately managing these conditions. This review guides clinicians in understanding the role of complement factors in systemic diseases and what diagnostic and therapeutic options are available for complement-mediated disorders.

From microscope to micropixels: A rapid review of artificial intelligence for the peripheral blood film.

Artificial intelligence (AI) and its application in classification of blood cells in the peripheral blood film is an evolving field in haematology. We performed a rapid review of the literature on AI and peripheral blood films, evaluating the condition studied, image datasets, machine learning models, training set size, testing set size and accuracy. A total of 283 studies were identified, encompassing 6 broad domains: malaria (n = 95), leukemia (n = 81), leukocytes (n = 72), mixed (n = 25), erythrocytes (n = 15) or Myelodysplastic syndrome (MDS) (n = 1). These publications have demonstrated high self-reported mean accuracy rates across various studies (95.5% for malaria, 96.0% for leukemia, 94.4% for leukocytes, 95.2% for mixed studies and 91.2% for erythrocytes), with an overall mean accuracy of 95.1%. Despite the high accuracy, the challenges toward real world translational usage of these AI trained models include the need for well-validated multicentre data, data standardisation, and studies on less common cell types and non-malarial blood-borne parasites.

Vacuum-Assisted Closure: An Effective Technique to Manage Wound Complications After Metastatic Spine Tumour Surgery (MSTS)-A Case Report.

The management of wound complications following metastatic spine tumor surgery (MSTS) remains a formidable task. Plastic coverage procedures after MSTS are challenging due to unhealthy donor sites following previous radiotherapy and prolonged nonambulation. Negative pressure wound therapy (NPWT) is usually not recommended after MSTS due to fear of tumor seeding and excessive blood loss. However, in certain patients post-MSTS, who may be considered as receiving palliative treatment, NPWT can be effective in managing wound complications. We describe our initial experience with the use of NPWT in a 57-year-old lady diagnosed with multiple lumbar and cervicothoracic vertebral metastases secondary to non-small cell lung carcinoma. She underwent 2 cycles of preoperative radiotherapy followed by decompression and posterior instrumentation of lumbosacral and cervicothoracic regions succeeded by another cycle of radiotherapy. The patient developed wound dehiscence and poly-microbial surgical site infection that was not responsive to regular debridements and antibiotics. Hence, we applied NPWT as an alternative treatment to plastic surgical procedures. The patient clinically improved with a reduced quantity of wound discharge, increased granulation tissue, and a downward trend in the inflammatory markers. Subsequently, wound was secondarily closed after 14 days. The patient was discharged after a total hospital stay of 41 days. The intravenous antibiotics (piperacillin/tazobactam) were changed to oral (ciprofloxacin) after 6 weeks and continued for 4 months. The patient survived for 3 years without any wound complications. Our case report suggests that NPWT can be a potential treatment option for managing wound complications following MSTS.

Factors influencing extended hospital stay in patients undergoing metastatic spine tumour surgery and its impact on survival.

Metastatic spine tumour surgeries (MSTS) are indicated for preservation or restoration of neurological function, to provide mechanical stability and pain alleviation. The goal of MSTS is to improve the quality of life of the patients with spinal metastases and rarely for oncological control which is usually achieved by adjuvant therapies. Hence outcome measures such as length of stay (LOS) and rate of complications after MSTS are important indicators of quality but there is limited literature evidence for the same. We carried out a retrospective study to determine the incidence and the factors influencing normal (nLOS) and extended length of stay (eLOS) after MSTS. Data of 220 consecutive patients who underwent MSTS between 2005 and 2015 were retrieved from hospital electronic records. The preoperative, intraoperative and postoperative variables, discharge destinations as well as socioeconomic factors were analyzed. eLOS defined as positive when the LOS exceeded the 75th percentile for this cohort, was the key outcome indicator. Univariate and multivariate logistic regression analyses were performed to determine the predictive factors of eLOS. The overall median LOS was 7 days (1-30 days) and 55 patients had eLOS (LOS ≥ 11 days). Multivariate analysis revealed that significant variables independently associated with eLOS were instrumentation >9 spinal segmental levels (OR 2.89, 95% CI 1.1-7.5, p = 0.032) and presence of postoperative complications (OR 3.68, 95% CI 1.85-7.30, p < 0.001). Metastatic tumours other than breast, prostate and lung have lesser risk of eLOS (OR 0.31, 95% CI 0.14-0.70, p = 0.004). Survival estimates show that patients with eLOS have shorter survival than patients with nLOS (Crude HR 1.81, 95% CI 1.13-2.89, p = 0.003).