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Alternating motion rate as an index of speech motor disorder in traumatic brain injury.

The task of syllable alternating motion rate (AMR) (also called diadochokinesis) is suitable for examining speech disorders of varying degrees of severity and in individuals with varying levels of linguistic and cognitive ability. However, very limited information on this task has been published for subjects with traumatic brain injury (TBI). This study is a quantitative and qualitative acoustic analysis of AMR in seven subjects with TBI. The primary goal was to use acoustic analyses to assess speech motor control disturbances for the group as a whole and for individual patients. Quantitative analyses included measures of syllable rate, syllable and intersyllable gap durations, energy maxima, and voice onset time (VOT). Qualitative analyses included classification of features evident in spectrograms and waveforms to provide a more detailed description. The TBI group had (1) a slowed syllable rate due mostly to lengthened syllables and, to a lesser degree, lengthened intersyllable gaps, (2) highly correlated syllable rates between AMR and conversation, (3) temporal and energy maxima irregularities within repetition sequences, (4) normal median VOT values but with large variation, and (5) a number of speech production abnormalities revealed by qualitative analysis, including explosive speech quality, breathy voice quality, phonatory instability, multiple or missing stop bursts, continuous voicing, and spirantization. The relationships between these findings and TBI speakers' neurological status and dysarthria types are also discussed. It was concluded that acoustic analyses of the AMR task provides specific information on motor speech limitations in individuals with TBI.

Adolescent↗

Outer membrane changes enable evolutionary escape from bacterial predation.

Antimicrobial resistance (AMR) is a threat to modern medicine. To combat AMR pathogens, natural predators like bacteriophages and predatory bacteria have gained interest recently. Predatory bacterium Bdellovibrio bacteriovorus is ubiquitous and has a broad prey range. It is particularly potent at killing many AMR Gram-negative bacterial pathogens featured on the WHO priority list. However, it is currently unclear whether prey bacteria can evolve genetically-determined resistance against predation by B. bacteriovorus. Here, we show that the model bacterium Escherichia coli K-12 consistently evolves resistance against B. bacteriovorus during experimental evolution. Selection for resistance scaled positively with predation pressure and was widespread after two cycles of predator exposure. Similar to antibiotics, predation resistance was costly, manifesting in a trade-off between predation resistance and fitness in the absence of predators. Genetic analysis combined with proteomics identified mutations that lead to the down-regulation of the outer membrane porin OmpF as a common resistance mechanism. In addition, a rarer mutation in cell envelope lipopolysaccharide-modifying enzyme WaaF also conferred predation resistance, likely by a pleiotropic effect, which included OmpF down regulation. While our study uncovers evolutionary and mechanistic aspects of prey escape from predation, it also highlights that the high cost of resistance reflects a handicap for the pathogen and can thus be exploited to increase treatment sustainability. Altogether, our work generates essential knowledge in ecologically important predator-prey interactions and can advance predatory bacteria as "living antibiotics" to combat AMR.

Bdellovibrio bacteriovorus↗

Phenotype-genotype discordance in antimicrobial resistance profiles of Gram-negative uropathogens recovered from catheter-associated urinary tract infections in Egypt.

OBJECTIVES: Catheter-associated urinary tract infections (CAUTIs) are among the most common healthcare-associated infections in low- and middle-income countries (LMICs), but there are few resistome data available for relevant uropathogens. The goal of this study was to characterize the antimicrobial resistance (AMR) phenotypes and genotypes of a large collection of Gram-negative bacteria recovered from CAUTIs in a hospital in Mansoura, Egypt. METHODS: Phenotypic AMR profiles and whole-genome sequence data were generated for 132 isolates. Resistomes were predicted using ResFinder, CARD and AMRFinder. Similarity of uropathogen genomic data was determined using sourmash (kmer signatures). Escherichia coli genomic data were subject to a pangenome analysis using Panaroo. RESULTS: Sixty-seven E. coli (Phylogroup B2; 53.7%, 36/67), 14 Pseudomonas aeruginosa, 11 Klebsiella pneumoniae, 9 Proteus mirabilis, 8 Providencia spp., 5 Enterobacter hormaechei and 18 rare CAUTI-associated isolates were identified. Several (22/132) isolates were multidrug-resistant, while almost half (62/132) were extensively drug-resistant. Phenotype-genotype discordance was found to be an important consideration in resistome studies in Egypt, with a total concordance of 91% (1115/1225), 85.7% (1273/1485) and 80.5% (1196/1485) for ResFinder, CARD and AMRFinder, respectively. Pseudomonas, at the species level, exhibited the greatest discordance. At the antimicrobial level, meropenem was subject to greatest discordance. New AMR variants were found for Egypt for Pseudomonas (blaOXA-486, blaOXA-488, blaOXA-905, blaIMP-43, blaPDC-35, blaPDC-45, blaPDC-201) and E. coli (blaTEM-176, blaTEM-190). CONCLUSIONS: This study shows that there is phenotype-genotype discordance in AMR profiling among CAUTI isolates, highlighting the need for comprehensive approaches in resistome studies. We also show the genomic diversity of Gram-negative uropathogens contributing to disease burden in a little-studied LMIC setting.

Egypt↗

Simultaneous recording of early and middle components of auditory electric response.

The auditory brain stem response (ABR) and the auditory middle response (AMR) were simultaneously recorded in 19 normal adults and 29 patients with hearing loss. The test was performed using tone pips at 0.5, 1, 2, and 4 kHz with intensity levels of 0, 10, 20, and 30 dB above the individual's behavioral threshold. A wide pass-band of 0.5 Hz to 3 kHz was used for recording the response. The typical waveform of the response provided six peaks that were successively labeled as P10, N15, P20, N25, P35, and N45. P10 was a large positive deflection in the ABR. N15-P20-N25, P35, and N45 corresponded to the Na peak complex, Pa, and Nb of the AMR, respectively. Of all components recorded, P10 was detected most consistently. However, because N25 and P35 of the AMR also gave important information for the assessment of hearing, simultaneous recording of the ABR and AMR is considered a useful clinical technique for estimating hearing in normal as well as in hearing-impaired subjects.

Acoustic Stimulation↗

Antibody-mediated rejection after adult ABO-incompatible liver transplantation remedied by gamma-globulin bolus infusion combined with plasmapheresis.

Adult ABO-incompatible liver transplantation has been known to be associated with markedly desperate outcomes. Antibody-mediated rejection (AMR) has been recognized as one of the primary causes of these desperate outcomes, but its clinical features and significance have not been well understood. Recently, some clinicians have succeeded in improving the outcome of adult ABO-incompatible liver transplantation. However, in some transplant patients undergoing these treatments, AMR has still led to graft losses. We recently encountered two patients suffering from AMR after adult ABO-incompatible liver transplantation and remedied their conditions with various therapeutic modalities including direct hepatic infusion therapy and gamma-globulin bolus infusion therapy combined with plasmapheresis. In this article, we describe the clinical features of these patients and the therapeutic strategies we applied. Furthermore, we show the histologic course of the recovery from AMR in the second patient, from whom we were able to extract serial liver biopsies.

ABO Blood-Group System↗

Genomic epidemiology and antimicrobial resistance profile of Shigella isolated from diarrhoea diseases in under-five children in Blantyre, Malawi.

Antimicrobial resistance (AMR) in Shigella is rising globally, complicating shigellosis management. Whole-genome sequence analysis (WGSA) has advanced our understanding of AMR and transmission dynamics, yet contemporary whole-genome sequencing data from Shigella in sub-Saharan Africa remain scarce. In this study, we applied WGSA to 27 Shigella isolates collected from children presenting with diarrhoea at Ndirande Health Centre in Malawi (2022-2023), as part of the Enterics for Global Health Shigella surveillance study. Serotyping, AMR profiling and phylogenetic analysis revealed Shigella sonnei as the dominant serogroup, with distinct genetic clustering relative to global reference strains among S. sonnei, Shigella flexneri and Shigella boydii. We identified 16 AMR genes linked to ten antimicrobial classes with qnrS1 and qnrB19 genes conferring resistance to fluoroquinolone, alongside IncFIB(K) and IncFII plasmid replicon markers. Importantly, no azithromycin resistance determinants were detected both genotypically and phenotypically, providing baseline evidence that warrants continued surveillance of current first-line treatment. However, the detection of fluoroquinolone resistance genes with plasmid replicon markers in the absence of phenotypic resistance might indicate a silent reservoir with epidemic potential. This is the first contemporary Shigella data from a large-scale diarrhoea disease surveillance study in Malawi, providing essential baseline information for guiding antibiotic treatment and future vaccine development efforts, contributing to the efforts to combat shigellosis in Malawi and other similar regions.

Humans↗

National conference to assess antibody-mediated rejection in solid organ transplantation.

The process of humoral rejection is multifaceted and has different manifestations in the various types of organ transplants. Because this process is emerging as a leading cause of graft loss, a conference was held in April 2003 to comprehensively address issues regarding humoral rejection. Though humoral rejection may result from different factors, discussion focused on a paradigm caused by antibodies, typically against donor HLA antigens, leading to the term 'antibody-mediated rejection' (AMR). Conference deliberations were separated into four workgroups: The Profiling Workgroup evaluated strengths and limitations of different methods for detecting HLA reactive antibody, and created risk assessment guidelines for AMR; The Diagnosis Workgroup reviewed clinical, pathologic, and serologic criteria for assessing AMR in renal, heart and lung transplant recipients; The Treatment Workgroup discussed advantages, limitations and possible mechanisms of action for desensitization protocols that may reverse AMR; and The Basic Science Workgroup presented animal and human immunologic models for humoral rejection and proposed potential targets for future intervention. This work represents a comprehensive review with contributions from experts in the fields of Transplantation Surgery, Medicine, Pathology, Histocompatibility, Immunology, and clinical trial design. Immunologic barriers once considered insurmountable are now consistently overcome to enable more patients to undergo organ transplantation.

Antibodies↗

Antibody-mediated rejection of a pancreas allograft.

The role of antibody-mediated rejection (AMR) in pancreas transplantation is poorly understood. Here, we report on a patient who developed AMR of his pancreas allograft after receiving a simultaneous pancreas-kidney transplant. Pre-operative enhanced cytotoxicity and flow cytometry T-cell crossmatches were negative; B-cell crossmatches were not performed as per institutional protocol. The patient's post-operative course was significant for elevated serum amylase levels and development of hyperglycemia approximately 1 month after transplantation. A pancreatic biopsy at this time showed no cellular infiltrate but strong immunofluorescent staining for C4d in the interacinar capillaries. Analysis of the patient's serum identified donor-specific HLA-DR alloantibodies. He received intravenous immunoglobulin (IVIg), rituximab and plasmapheresis, and his pancreatic function normalized. We conclude that clinically significant AMR can develop in a pancreas allograft and recommend that pancreatic biopsies be assessed for C4d deposition if the patient has risk factors for AMR and/or the pathologic evidence for cell-mediated rejection is underwhelming.

Adult↗

Phosphorylated S6 ribosomal protein: a novel biomarker of antibody-mediated rejection in heart allografts.

We tested the hypothesis that phosphorylation of S6 ribosomal protein (S6RP), a downstream target of the PI3K/Akt/mTOR pathway, is a biomarker of antibody-mediated rejection (AMR) in heart allografts. Primary cultures of human aortic and microvascular endothelial cells (EC) were treated with anti-HLA class I and class II antibodies (Ab) and cell lysates were studied for phosphorylation of S6 ribosmal protein at Serine235/236 (p-S6RP). Treatment of cultured EC with anti-class I and class II Ab stimulated S6RP phosphorylation. Immunohistochemical techniques were used to detect the level of p-S6RP in endomyocardial biopsies (n = 131) from 46 heart transplant recipients and the results were correlated with histopathological diagnosis of rejection, C4d staining, production of posttransplant anti-HLA Ab and clinical outcome. Increased phosphorylation of S6RP in endomyocardial biopsies was significantly associated with the diagnosis of AMR (p < 0.0001). No significant association between acute cellular rejection (ACR) and p-S6RP was observed. C4d staining was positively associated with both AMR and p-S6RP. Posttransplant anti-HLA class II Ab production was also significantly associated with a positive p-S6RP status in cardiac biopsies. These results indicate that p-S6RP is a useful biomarker for the diagnosis of AMR.

Acute Disease↗

Clinical carbapenem-resistant Enterobacterales in a University Hospital in Dakar, Senegal: genomic insights into Enterobacter hormaechei ST182 strains carrying blaNDM-5 and blaOXA-48 genes&#x2003;.

Senegal has witnessed the emergence and spread of carbapenem-resistant Enterobacterales (CRE), which often cause deadly infections. Accordingly, this study aimed to determine the antimicrobial susceptibility and prevalence of carbapenemases, as well as to perform a whole-genome sequence analysis of clinical CRE isolates from a university hospital in Dakar, Senegal. MALDI-TOF MS and VITEK2 systems were used for bacterial identification and antimicrobial susceptibility testing (AST). Carbapenemase- and cephalosporinase-encoding genes were screened using simplex end-point polymerase chain reaction. Whole-genome sequencing (WGS) was performed using the Illumina MiSeq platform. The CRE isolates were resistant to almost all the 34 antimicrobials tested. Nevertheless, colistin and amikacin remained active, with susceptibility rates of 96% and 71%, respectively. Only the carbapenemase genes blaOXA-48 (53.8%; 15/28) and blaNDM (35.7%; 10/28) and the cephalosporinase gene blaCMY-1 (25%; 7/28) were identified. In this context, two extensively drug-resistant Enterobacter hormaechei isolates were subjected to WGS analysis. These isolates were assigned as sequence type (ST) 182 and carried several genes related to antimicrobial resistance (AMR), metal tolerance, and virulence. An IncL/M plasmid with 61,054 bp in length was identified as carrying the blaOXA-48 gene, whereas an IncFIB(pECLA)/IncFII(pECLA)/IncX3 mutireplicon plasmid with 217,745 bp in length was detected as harboring the blaNDM-5 gene and other genes related to AMR and metal tolerance. Our study presents the first landscape of clinical CRE circulating in Senegal, along with additional genomic analysis of E. hormaechei ST182 strains, which could be useful for mitigating the burden associated with CRE in this country.IMPORTANCEThe investigation of global critical priority CRE isolates has become crucial to reduce morbidity and mortality associated with AMR. This study revealed that colistin and amikacin can be considered good alternatives for treating CRE-associated infections in Dakar. In addition, the genomic approach revealed that the CRE isolates carried both a wide resistome and virulome. Moreover, the abundance of horizontal gene transfer regions in the genomes suggests the great implications of mobile genetic elements in the spread of AMR in Dakar. Furthermore, this study reported the complete sequences of chromosomes and blaOXA-48 and blaNDM-5-carrying plasmids. Our findings are of great importance because complete genome sequences are still rarely characterized in the West African region. Finally, this study highlights the importance of strengthening genomic surveillance of CRE in sub-Saharan African countries to mitigate the burden associated with these pathogens.

Senegal↗

Symptomatic differences in decreased alternating motion rates between individuals with spastic and with ataxic dysarthria: an acoustic analysis.

Acoustic analysis was conducted to investigate symptomatic differences in decreased oral alternating motion rates (AMRs) between individuals with spastic and with ataxic dysarthria. The subjects were 6 individuals with spastic dysarthria, 6 with ataxic dysarthria and 6 normal speakers. Monosyllables /pa/ and /ta/ were used to examine alternating motions of the lips and tongue, respectively. In the decreased AMRs of the spastic group, the mean syllable durations were generally longer in the individuals where the mean total syllable durations were longer, and in the decreased AMRs of the ataxic group, the mean gap durations were generally longer in the individuals where the mean total syllable durations were longer. It was suggested that each syllable component could represent a separate function and contribute differently to the decreased AMRs in these dysarthric groups.

Adult↗

Behaviour of motor unit action potential rate, estimated from surface EMG, as a measure of muscle activation level.

BACKGROUND: Surface electromyography (EMG) parameters such as root-mean-square value (RMS) are commonly used to assess the muscle activation level that is imposed by the central nervous system (CNS). However, RMS is influenced not only by motor control aspects, but also by peripheral properties of the muscle and recording setup. To assess motor control separately, the number of motor unit action potentials (MUAPs) per second, or MUAP Rate (MR) is a potentially useful measure. MR is the sum of the firing rates of the contributing MUs and as such reflects the two parameters that the CNS uses for motor control: number of MUs and firing rate.MR can be estimated from multi-channel surface EMG recordings. The objective of this study was to explore the behaviour of estimated MR (eMR) in relation to number of active MUs and firing rate. Furthermore, the influence of parameters related to peripheral muscle properties and recording setup (number of fibers per MU, fiber diameter, thickness of the subcutaneous layer, signal-to-noise-ratio) on eMR was compared with their influence on RMS. METHODS: Physiological parameters were varied in a simulation model that generated multi-channel EMG signals. The behaviour of eMR in simulated conditions was compared with its behaviour in experimental conditions. Experimental data was obtained from the upper trapezius muscle during a shoulder elevation task (20-100 N). RESULTS: The simulations showed strong, monotonously increasing relations between eMR and number of active MUs and firing rate (r(2) > 0.95). Because of unrecognized superimpositions of MUAPs, eMR was substantially lower than the actual MUAP Rate (aMR). The percentage of detected MUAPs decreased with aMR, but the relation between eMR and aMR was rather stable in all simulated conditions. In contrast to RMS, eMR was not affected by number of fibers per MU, fiber diameter and thickness of the subcutaneous layer. Experimental data showed a strong relation between eMR and force (individual second order polynomial regression: 0.96 < r(2) < 0.99). CONCLUSION: Although the actual number of MUAPs in the signal cannot be accurately extracted with the present method, the stability of the relation between eMR and aMR and its independence of muscle properties make eMR a suitable parameter to assess the input from the CNS to the muscle at low contraction levels non-invasively.

Journal Article↗

Genomics for precision surgical source control in anti-microbial resistant infections: A global review with focus on resource-limited settings.

BACKGROUND & OBJECTIVE: Antimicrobial resistance (AMR) critically threatens surgical safety, impairing perioperative prophylaxis and complicating infection management. Timely surgical source control is essential but relies on accurate microbiological diagnosis. Conventional culture-based methods are slow and insensitive, often leading to empirical broad-spectrum therapy. This review evaluates the role of advanced genomic diagnostics in enhancing surgical source control for AMR infections, with a focus on challenges and opportunities in low- and middle-income countries (LMICs) like Pakistan. METHODOLOGY: A narrative review was conducted via a structured search of PubMed, Google Scholar, and ScienceDirect (January 2015-October 2025). Studies involving genomic tools in the management of AMR-related surgical infections were included. Evidence was synthesized thematically, covering genomic platforms, clinical applications, implementation barriers, and LMIC specific perspectives. RESULTS: Genomic tools, particularly metagenomic next-generation sequencing (mNGS) and rapid multiplex PCR, demonstrate superior sensitivity (80.6-95.45%) and faster turnaround times (e.g., roughly 27 hours for mNGS) compared to culture. They improve pathogen detection in complex infections (e.g., prosthetic joints, necrotizing soft tissue), guide targeted antibiotic therapy, and can reduce broad-spectrum use. However, major implementation barriers exist, including high costs, need for specialized infrastructure and expertise, bioinformatic challenges, and ethical data concerns, which are especially pronounced in LMICs. CONCLUSION: Genomic diagnostics offer a powerful approach to accelerate and refine surgical source control in the era of AMR. Strategic investments in local capacity, affordable platforms, and integration with antimicrobial stewardship are needed to realize their potential for improving surgical outcomes, particularly in resource-limited settings.

Antimicrobial resistance↗

Versatile wastewater monitoring of pathogens and antimicrobial resistance enabled by metatranscriptomics and long-read metagenomics.

Widespread interest in the development of population-wide pathogen and antimicrobial resistance (AMR) monitoring has revealed wastewater's microbial footprint as a marker of public health. Near-source wastewater remains a difficult sample type for microbiome analyses but represents a closer link to human health than the downstream products of its treatment. Few studies integrate methods for non-targeted monitoring applications, and critically, current methods cannot connect AMR genes to species, nor resolve full genomes. We address these challenges by developing a pipeline that enables untargeted metagenomics, metatranscriptomics, and novel long-read metagenomics (LRG). We achieve untargeted pathogen detection, limited by highly abundant resident species, while retaining microbial information with near-source sampling. Furthermore, LRG identifies antibiotic resistance gene-containing microbes and enables assembly of culture-independent genomes with previously unreported AMR genes. We establish an integrated approach to broadly monitor pathogens in wastewater, while demonstrating the importance of LRG to illuminate microbial AMR at the species level.

Journal Article↗

Mobilome-driven antimicrobial resistance in a one health context: evidence and lessons from Africa.

Antimicrobial resistance (AMR) is one of the most urgent global health threats and is increasingly recognized as a One Health challenge driven by interactions among human, animal, and environmental reservoirs. Central to the emergence and dissemination of AMR across these interfaces are mobile genetic elements (MGEs), which form an interconnected mobilome capable of transferring resistance genes across bacterial taxa and ecological niches. These elements facilitate the accumulation and spread of multidrug resistance determinants and are shaped by co-selective pressures operating at the animal-environment-human interface. Despite their critical role, genomic surveillance of MGEs remains limited, particularly in high-burden regions such as Africa. This narrative review synthesizes evidence from published genomic surveillance studies, primarily whole-genome sequencing-based analyses, to examine the distribution and dynamics of AMR genes and MGEs across One Health interfaces. We highlight animal-environmental systems as major hotspots for mobilome-driven resistance dissemination and also evaluate key advances, methodological approaches, and persistent surveillance challenges and gaps specific across Africa. By integrating findings from diverse genomic studies, and highlighting key lessons and implementation gaps from One Health studies across Africa, this review underscores the need for coordinated One Health surveillance strategies to better capture mobilome dynamics and inform sustainable AMR control efforts.

Africa↗

An evaluation of methods for the detection of spinal cord in product derived from advanced meat recovery systems.

This study investigated the usefulness of immunohistochemistry, histochemistry, and polarization microscopy in documenting the presence of spinal cord in ground product produced by advanced meat recovery systems (AMRS). A battery of diagnostic stains proved most helpful for definitive documentation of spinal cord in the AMRS product. Antibodies to neurofilament and glial fibrillary acidic proteins were useful for highlighting the presence of neural tissue in comminuted product but when used alone did not definitively differentiate central nervous system tissue from peripheral nerve. Polariscopy, trichrome staining, and immunostaining for synaptophysin were very useful for differentiating spinal cord from peripheral nerve. Spinal cord was found in 2 of 196 AMRS samples when only hematoxylin and eosin staining was used. In a later immunohistochemical subset of the survey study, spinal cord was found in 7 of 17 AMRS samples. More recently, spinal cord tissue has been found in 3 of 26 regulatory samples using hematoxylin and eosin stains combined with immunohistochemical techniques.

Animals↗

A Decade of Achievements and Future Directions in Global Antimicrobial Resistance Surveillance System in Korea (Kor-GLASS).

OBJECTIVES: To comprehensively evaluate the 10-year operational outcomes (2016-2025) Global Antimicrobial Resistance Surveillance System in Korea (Kor-GLASS), assess its public health significance for national stewardship and global surveillance, and propose strategies for future development. METHODS: The study described the operational framework of Kor-GLASS, including its strain collection, analysis, and quality control systems, based on surveillance data. It analyzed resistance trends among key bloodstream pathogen isolates collected from 2016 to 2024 and evaluated major achievements, including alignment with the World Health Organization (WHO)'s Global Antimicrobial Resistance Surveillance System (GLASS), integration with the Emerging Antimicrobial Resistance Reporting (EAR) system, and activities as a WHO Collaborating Centre. RESULTS: Kor-GLASS operates on a foundation of standardized, isolate-based surveillance supported by an independent quality management system that complies with WHO GLASS standards. In alignment with the strategic direction of WHO GLASS, the surveillance scope has progressively expanded in terms of catchment areas, target pathogens, specimen types, and antimicrobial panels. From 2016 to 2024, a total of 116,955 clinical isolates were collected and analyzed through the network of collection and analysis centers. This has enabled the continuous generation of nationally representative antimicrobial resistance (AMR) data from general hospitals. The accumulated surveillance data provide fundamental evidence for tracking long-term resistance trends and elucidating the molecular epidemiological characteristics of key pathogens. These outcomes are disseminated through the publication of the "National Antimicrobial Resistance Surveillance Annual Report" and data submissions to WHO GLASS and GLASS-EAR, thereby supporting both national and global AMR surveillance efforts. Furthermore, Kor-GLASS has strengthened international surveillance and One Health collaboration capacities through its designation and redesignation as a WHO Collaborating Centre for AMR Surveillance. CONCLUSIONS: Over the past decade, Kor-GLASS has served as the cornerstone of national antimicrobial resistance surveillance, providing evidence to inform policy and supporting global surveillance systems. Moving forward, Kor-GLASS is expected to evolve into a pivotal national AMR surveillance system through the introduction of whole-genome sequencing and stronger integration with national antimicrobial consumption surveillance.

Anti-bacterial agents↗

A phase I study of irinotecan in combination with amrubicin for advanced lung cancer patients.

BACKGROUND: A combination phase I study was conducted in a cohort of lung cancer patients to determine the maximum tolerated dose (MTD) and toxicities of irinotecan (CPT-11), a topoisomerase I inhibitor, in combination with amrubicin (AMR), a topoisomerase II inhibitor, and to observe their antitumor activities. PATIENTS AND METHODS: Patients with lung cancer received AMR (35 - 40 mg/m2 given intravenously over 5 min) for 3 consecutive days, and CPT-11 (50 - 60 mg/m2 given intravenously over 90 min) after the completion of AMR infusion on days 1 and 8, every 3 weeks. RESULTS: In total, eleven patients were enrolled in this study. The most frequent toxicities were bone marrow suppression, particularly leucopenia and neutropenia, followed by infection, diarrhea and pneumonitis. As a consequence of these toxicities, the MTD and the recommended dose could not be determined. There were two partial responses, which included one patient with small cell lung cancer (SCLC) who had previously received chemotherapy and the other with previously untreated non-small cell lung cancer (NSCLC). CONCLUSION: These data suggest that the combination of CPT-11 and AMR is not tolerated, as it mediates an unexpectedly strong myelosuppressive effect, and is inactive against both NSCLC and SCLC.

Aged↗