Megapneumonia Coinfection: pneumococcus, Mycoplasma pneumoniae,

We report a young girl who died of Streptococcus pneumoniae 19A pneumonia, septic shock, and hemolytic uremic syndrome despite prior pneumococcal vaccination, appropriate antibiotics, and aggressive intensive care support. Serotype 19A is not covered by the 7- or 10-valent pneumococcal vaccines. Mycoplasma pneumoniae and metapneumovirus were simultaneously detected by PCR in the nasopharyngeal and tracheal aspirates. The pneumococcus is penicillin sensitive. Although infections with each of these pathogens alone are typically mild, this case highlights that co-infection with the triple respiratory pathogens possibly contributed to the fatal outcome of this child. Also, the new policy in Hong Kong to use PCV13 may help prevent further cases of serotype 19A infections

Spot diagnosis: An ominous rash in a newborn

Purpura fulminans (PF) is an ominous cutaneous condition usually associated with meningococcemia. PF in the newborn is rarely reported. We report the case of a female preterm infant with extensive PF due to group B streptococcus (GBS) septicemia. She developed multi-organ system failure despite neonatal intensive care support and succumbed 9 days later. GBS, sensitive to penicillin, was isolated from the blood cultures of the mother and the infant. Invasive early GBS infection is common in the newborn and is empirically treated with prompt institution of intravenous antibiotics. PF associated with GBS is a rare cutaneous sign that must not be missed. Mortality remains high despite aggressive treatment and ICU support

Treatment with Methylphenidate for Attention Deficit Hyperactivity Disorder (ADHD) and the Risk of All-Cause Poisoning in Children and Adolescents:A Self-Controlled Case Series Study

BACKGROUND: Children and adolescents with attention deficit hyperactivity disorder (ADHD) are at higher risk of all-cause poisoning by drugs and chemicals (intentional or accidental). Currently, there is limited data on whether medication treatment for ADHD can reduce the risk of all-cause poisoning. METHODS: Patients aged 5–18 years with a methylphenidate (MPH) prescription and an incident poisoning diagnosis between January 2001 and June 2020 were identified from the Hong Kong Clinical Data Analysis and Reporting System. A self-controlled case series study design was used to compare the incidence rate ratios (IRRs) of all-cause poisoning during different risk windows (30 days before the first MPH prescription, exposure periods within 30 days of the first prescription, and periods of subsequent exposure) compared with the reference window (other non-exposure periods). RESULTS: 42,203 patients were prescribed ADHD medication in Hong Kong during the study period. Of these, 417 patients who had both an MPH prescription and poisoning incident recorded were included in the main analysis. Compared with other non-exposed periods, a higher risk of poisoning was found in the 30 days before the first prescription (IRR 2.64, 95% confidence interval [CI] 1.33–5.22) and exposure periods within 30 days of the first prescription (IRR 2.18, 95% CI 1.06–4.48), but not during prolonged exposure. However, compared with 30 days before the first prescription as well as exposure periods within 30 days of the first prescription, there was a lower risk during the subsequent exposure (IRRs 0.49 and 0.60, respectively). Similar results to the main analysis were also found in the subgroup analysis of intentional poisoning and females, but not in that of accidental poisoning and males. CONCLUSIONS: The risk of all-cause poisoning was higher shortly before and after the first MPH prescription and became lower during the subsequent prescription period. Our results do not support an association between the use of MPH and an increased risk of all-cause poisoning in children and adolescents and, in fact, suggest that longer-term use of MPH may be associated with a lower risk of all-cause poisoning, although this latter finding requires further study. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40263-021-00824-x

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease

Discovery of an Abundance of Biosynthetic Gene Clusters in Shark Bay Microbial Mats

Biosynthetic gene clusters identified in Shark Bay microbial mat

New Approaches to Detect Biosynthetic Gene Clusters in the Environment

Microorganisms in the environment can produce a diverse range of secondary metabolites (SM), which are also known as natural products. Bioactive SMs have been crucial in the development of antibiotics and can also act as useful compounds in the biotechnology industry. These natural products are encoded by an extensive range of biosynthetic gene clusters (BGCs). The developments in omics technologies and bioinformatic tools are contributing to a paradigm shift from traditional culturing and screening methods to bioinformatic tools and genomics to uncover BGCs that were previously unknown or transcriptionally silent. Natural product discovery using bioinformatics and omics workflow in the environment has demonstrated an extensive distribution of BGCs in various environments, such as soil, aquatic ecosystems and host microbiome environments. Computational tools provide a feasible and culture-independent route to find new secondary metabolites where traditional approaches cannot. This review will highlight some of the advances in the approaches, primarily bioinformatic, in identifying new BGCs, especially in environments where microorganisms are rarely cultured. This has allowed us to tap into the huge potential of microbial dark matter

Rocking the cradle of life: Illuminating the microbiome of microbial mats from Shark Bay using genome-resolved metagenomic analyses

Microbial mats are modern analogues of ancient stromatolites on Precambrian Earth. Microbial mats are ideal ecological systems to study microbial and functional diversity adapting to extreme environments. Prior to this study, little was known of the phylogenetic diversity and functional capacity of the uncultivated microorganisms in the iconic systems in Shark Bay. This dissertation aims to elucidate the phylogenetic diversity of archaeal communities, functional genetic capacity of the overall microbial mat microbiome, and the role of microbial dark matter in Shark Bay mats. Amplicon sequencing at a millimetre scale coupled with microelectrode measurements have revealed novel archaeal groups such as Asgard and DPANN archaea for the first time in these systems. This approach increased resolution at the taxonomic level and reinforced the proposal of a surface anoxic niche. Genome-resolved metagenomics have revealed complex biogeochemical cycles and adaptive responses in smooth mats, as well as high capacities of sulfur and Wood-Ljungdahl metabolisms. High abundances of copper resistance and phosphate intake genes corroborates with the high copper concentration and extremely low phosphorus concentration measured in Shark Bay. Pathways of environmental adaptation (UV, hypersalinity, and heavy metal resistance) were also delineated, as well as putative viral defensive mechanisms (CRIPSR. BREX and DISARM). For the first time metagenome-assembled genomes (MAGs) affiliated to microbial dark matter were reconstructed in Shark Bay microbial mats, spanning across 33 phyla within bacterial and archaeal domains. In addition, this dissertation reports for the first time evidence of candidate phylum GN15 putatively taking part in dissimilatory sulfate reduction, as well as diversity-generating retroelements (DGRs) present in Asgard archaea. Microbial dark matter MAGs encode minimum-sized genomes and lack complete biosynthetic pathways, yet are proposed to have a role in recycling organic carbon in the Shark Bay mats. Various forms of RuBisCo were found in microbial dark matter MAGs, along with carbon monoxide dehydrogenase and high abundance of hydrogenases, suggesting that H2, CO2/CO and ribose as prominent currencies among microbial dark matter communities. The results of this dissertation highlight vast microbial and functional diversity, ‘hot spots’ of critical functions, and provide putative models for intricate microbial interactions driving these evolutionarily significant systems