High Mycobacterium tuberculosis Bacillary Loads Detected by Tuberculosis Molecular Bacterial Load Assay in Patient Stool: a Potential Alternative for Nonsputum Diagnosis and Treatment Response Monitoring of Tuberculosis

This paper highlights the value of stool as a sample type for diagnosis of tuberculosis. While other studies have used DNA-based assays like the Xpert MTB/RIF and culture to detect Mycobacterium tuberculosis in stool, this is the first study that has applied TB-MBLA, an RNA-based assay, to quantify TB bacteria in stool.

Comparison of double-stranded and single-stranded cfDNA library construction methods for targeted genome and methylation sequencing

Cell-free DNA (cfDNA) profiling by deep sequencing (i.e., by next generation sequencing (NGS)) has wide applications in cancer diagnosis, prognosis, and therapy response monitoring. One key step of cfDNA deep sequencing workflow is NGS library construction, whose efficiency significantly affects the utilization efficiency of cfDNA molecules, and eventually determines effective sequencing depth and sequencing accuracy. In this study, we compared two different types of cfDNA library construction methods, namely double-stranded library (dsLib, the conventional method which captures dsDNA molecules) and single-stranded library (ssLib) preparation, which captures ssDNA molecules, for the applications of mutation detection and methylation profiling, respectively. Our results suggest that the dsLib method was suitable for mutation detection while the ssLib method proved more efficient for methylation analysis. Our findings could help researchers choose the more appropriate library construction method for corresponding downstream applications of cfDNA sequencing.

Complete remission in a patient with widely metastatic HER2-amplified pancreatic adenocarcinoma following multimodal therapy informed by tumor sequencing and organoid profiling

This work, "Complete remission in a patient with widely metastatic HER2-amplified pancreatic adenocarcinoma following multimodal therapy informed by tumor sequencing and organoid profiling" highlights the power of multi-institution collaboration, combining strengths in organoid profiling (Kuo group at Stanford), personalized vaccine therapy (Gillanders group at WUSTL), in vitro drug testing and drug sensitivity (SEngine, MSK, and Mprobe), clinical trials (Dr Ari Baron at CPMC), and the Canopy Health learning network. Here, we demonstrate a complete clinical response achieved in a patient with HER2+ metastatic pancreatic ductal adenocarcinoma to a coordinated barrage of anti-HER2, personalized vaccine and checkpoint inhibition immunotherapy, radiation, and chemotherapy. Comprehensive organoid profiling with drug sensitivity screening and drug testing suggested a vulnerability to anti-HER2 directed therapy, facilitating personalized treatment selection for our patient, which contributed to her clinical benefit. Immune response monitoring following personalized vaccine, radiation and checkpoint inhibition showed a sustained increase in neoantigen specific T cell response.

Humoral and cellular responses to SARS-CoV-2 vaccination in patients with lymphoid malignancies

SUMMARYSARS-CoV-2 vaccination protects against COVID-19. Antibodies and antigen-specific T-cell responses against the spike domain can be used to measure vaccine immune response. Individuals with lymphoma have defects in humoral and cellular immunity that may compromise vaccine response. In this prospective observational study of 457 participants with lymphoma, 52% of participants vaccinated on treatment had undetectable anti-spike IgG antibodies compared to 9% who were not on treatment. Marked impairment was observed in those receiving anti- CD20 antibody within 12 months where 60% had undetectable antibodies compared to 11% on chemotherapy, which persisted despite three vaccine doses. Overall, 63% had positive T-cell responses irrespective of treatment. Individuals with indolent B-cell lymphoma have impaired antibody and cellular responses that were independent of treatment. The significant reduction and heterogeneity in immune responses in these individuals emphasise the urgent need for immune response monitoring and alternative prophylactic strategies to protect against COVID- 19.

Molecular Targeted Positron Emission Tomography Imaging and Radionuclide Therapy of Pancreatic Ductal Adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) has an inauspicious prognosis, mainly due to difficulty in early detection of the disease by the current imaging modalities. The upcoming development of tumour-specific tracers provides an alternative solution for more accurate diagnostic imaging techniques for staging and therapy response monitoring. The future goal to strive for, in a patient with PDAC, should definitely be first to receive a diagnostic dose of an antibody labelled with a radionuclide and to subsequently receive a therapeutic dose of the same labelled antibody with curative intent. In the first part of this paper, we summarise the available evidence on tumour-targeted diagnostic tracers for molecular positron emission tomography (PET) imaging that have been tested in humans, together with their clinical indications. Tracers such as radiolabelled prostate-specific membrane antigen (PSMA)—in particular, 18F-labelled PSMA—already validated and successfully implemented in clinical practice for prostate cancer, also seem promising for PDAC. In the second part, we discuss the theranostic applications of these tumour-specific tracers. Although targeted radionuclide therapy is still in its infancy, lessons can already be learned from early publications focusing on dose fractioning and adding a radiosensitiser, such as gemcitabine.

Sputum microbiota profiles of treatment-naïve TB patients in Uganda before and during first-line therapy

Information on microbiota dynamics in pulmonary tuberculosis (TB) in Africa is scarce. Here, we sequenced sputa from 120 treatment-naïve TB patients in Uganda, and investigated changes in microbiota of 30 patients with treatment-response follow-up samples. Overall, HIV-status and anti-TB treatment were associated with microbial structural and abundance changes. The predominant phyla were Bacteroidetes, Firmicutes, Proteobacteria, Fusobacteria and Actinobacteria, accounting for nearly 95% of the sputum microbiota composition; the predominant genera across time were Prevotella, Streptococcus, Veillonella, Haemophilus, Neisseria, Alloprevotella, Porphyromonas, Fusobacterium, Gemella, and Rothia. Treatment-response follow-up at month 2 was characterized by a reduction in abundance of Mycobacterium and Fretibacterium, and an increase in Ruminococcus and Peptococcus; month 5 was characterized by a reduction in Tannerella and Fusobacterium, and an increase in members of the family Neisseriaceae. The microbiota core comprised of 44 genera that were stable during treatment. Hierarchical clustering of this core’s abundance distinctly separated baseline (month 0) samples from treatment follow-up samples (months 2/5). We also observed a reduction in microbial diversity with 9.1% (CI 6–14%) of the structural variation attributed to HIV-status and anti-TB treatment. Our findings show discernible microbiota signals associated with treatment with potential to inform anti-TB treatment response monitoring.

Hemophagocytic Lymphohistiocytosis as Initial Presentation of Malignancy in Pediatric Patients: Rare but Not to Be Ignored

It is complicated to establish a consensus on the management and diagnosis of malignancy-triggered hemophagocytic lymphohistiocytosis (M-HLH) in children, as an initial presentation of malignancy is complicated. In this paper, we analyze the clinical characteristics and outcomes of eight pediatric patients in which M-HLH was the initial presentation of malignancy. All patients had hematologic malignancies: three subcutaneous panniculitis-like T-cell lymphomas, two acute lymphoblastic leukemias, two anaplastic large cell lymphomas, and a systemic EBV + T-cell lymphoma of childhood. The incidence rate of M-HLH among leukemia and malignant lymphoma patients in our institution was 1.9%. From the initial diagnosis of HLH, the median time taken to be diagnosed as a malignancy was about 1.3 months. The majority of patients received HLH-targeted immunosuppression and/or etoposide at first. The patients’ clinical response to treatment for HLH and malignancies were varied. Five out of the eight patients died, one of whom died due to HLH-related cerebral edema after the initiation of chemotherapy. The median overall survival was 1.6 years. In order to improve the survival rate, the early detection of M-HLH, rapid screening for malignancy, and complete control of M-HLH with HLH-directed therapy followed by a thorough response monitoring are required.