Integration of Genomic and Transcriptional Features in Pancreatic Cancer Reveals Increased Cell Cycle Progression in Metastases

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Genomic analysis of inherited breast cancer among Palestinian women: Genetic heterogeneity and a founder mutation in TP53

Breast cancer among Palestinian women has lower incidence than in Europe or North America, yet is very frequently familial. We studied genetic causes of this familial clustering in a consecutive hospital‐based series of 875 Palestinian patients with invasive breast cancer, including 453 women with diagnosis by age 40, or with breast or ovarian cancer in a mother, sister, grandmother or aunt (“discovery series”); and 422 women diagnosed after age 40 and with negative family history (“older‐onset sporadic patient series”). Genomic DNA from women in the discovery series was sequenced for all known breast cancer genes, revealing a pathogenic mutation in 13% (61/453) of patients. These mutations were screened in all patients and in 300 Palestinian female controls, revealing 1.0% (4/422) carriers among older, nonfamilial patients and two carriers among controls. The mutational spectrum was highly heterogeneous, including pathogenic mutations in 11 different genes: BRCA1, BRCA2, TP53, ATM, CHEK2, BARD1, BRIP1, PALB2, MRE11A, PTEN and XRCC2. BRCA1 carriers were significantly more likely than other patients to have triple negative tumors (p = 0.03). The single most frequent mutation was TP53 p.R181C, which was significantly enriched in the discovery series compared to controls (p = 0.01) and was responsible for 15% of breast cancers among young onset or familial patients. TP53 p.R181C predisposed specifically to breast cancer with incomplete penetrance, and not to other Li‐Fraumeni cancers. Palestinian women with young onset or familial breast cancer and their families would benefit from genetic analysis and counseling.     

Vaccination Decreases the Infectious Viral Load of Delta Variant SARS-CoV-2 in Asymptomatic Patients

The Delta variant of SARS-CoV-2 has caused many breakthrough infections in fully vaccinated individuals. While vaccine status did not generally impact the number of viral RNA genome copies in nasopharyngeal swabs of breakthrough patients, as measured by Ct values, it has been previously found to decrease the infectious viral load in symptomatic patients. We quantified the viral RNA, infectious virus, and anti-spike IgA in nasopharyngeal swabs collected from individuals asymptomatically infected with the Delta variant of SARS-CoV-2. Vaccination decreased the infectious viral load, but not the amount of viral RNA. Furthermore, vaccinees with asymptomatic infections had significantly higher levels of anti-spike IgA in their nasal secretions compared to unvaccinated individuals with asymptomatic infections. Thus, vaccination may decrease the transmission risk of Delta, and perhaps other variants, despite not affecting the amount of viral RNA measured in nasopharyngeal swabs.     

Performing under Pressure: Insights into the Diagnostic Testing Burden at a UK National Health Service Clinical Virology Laboratory during the SARS-CoV-2 Pandemic

UK National Health Service (NHS) Clinical Virology Departments provide a repertoire of tests on clinical samples to detect the presence of viral genomic material or host immune responses to viral infection. In December 2019, a novel coronavirus (SARS-CoV-2) emerged which quickly developed into a global pandemic; NHS laboratories responded rapidly to upscale their testing capabilities. To date, there is little information on the impact of increased SARS-CoV-2 screening on non-SARS-CoV-2 testing within NHS laboratories. This report details the virology test requests received by the Leicester-based NHS Virology laboratory from January 2018 to May 2022. Data show that in spite of a dramatic increase in screening, along with multiple logistic and staffing issues, the Leicester Virology Department was mostly able to maintain the same level of service for non-respiratory virus testing while meeting the new increase in SARS-CoV-2 testing.     

Epidemiological Aspects of Equid Herpesvirus-Associated Myeloencephalopathy (EHM) Outbreaks

Equid Herpesvirus Myeloencephalopathy (EHM) is a multifactorial disease following an EHV-1 infection in Equidae. We investigated a total of 589 horses on 13 premises in Europe in search of risk factors for the development of EHM. We found that fever (p < 0.001), increasing age (p = 0.032), and female sex (p = 0.042) were risk factors for EHM in a logistic mixed model. Some breeds had a decreased risk to develop EHM compared to others (Shetland and Welsh ponies; p = 0.017; p = 0.031), and fewer EHV-1-vaccinated horses were affected by EHM compared to unvaccinated horses (p = 0.02). Data evaluation was complex due to high variability between outbreaks with regards to construction and environment; viral characteristics and the virus’s transmissibility were affected by operational management. This study confirms earlier suspected host-specific risk factors, and our data support the benefit of high vaccine coverage at high-traffic boarding facilities.     

Ancillary treatment of patients with lung disease due to non-tuberculous mycobacteria: a narrative review

Background and ObjectiveNon-tuberculous mycobacterial lung disease (NTM-LD) manifests with bronchiectasis, inflammatory bronchiolitis, nodules, and/or cavitation. Bronchiectasis is characterized by permanently dilated airways wherein mucus accumulates, creating a vicious cycle of chronic injurious inflammation and recurrent infections. While antibiotics are an important part of the treatment of NTM-LD, airway clearance techniques to mitigate this pathogenic mechanism of bronchiectasis as well as other ancillary measures are also important components of NTM-LD treatment. The objective of this contemporaneous Narrative Review is to emphasize the importance of such ancillary measures.MethodsWe searched PubMed for the key words of “airway clearance”, “pulmonary rehabilitation”, “nutrition”, “swallowing dysfunction”, “gastroesophageal reflux”, “vestibular dysfunction”, or “cochlear dysfunction” with that of “non-tuberculous mycobacterial lung disease”, “bronchiectasis”, or “respiratory disease”. The bibliographies of identified articles were further searched for relevant articles not previously identified. Each relevant article was reviewed by one or more of the authors and a narrative review was composed.Key Content and FindingsHerein, we discuss five ancillary treatment measures that are pertinent to patients with bronchiectasis and NTM-LD: (I) airway clearance; (II) physical and pulmonary rehabilitation; (III) nutrition; (IV) diagnosis and mitigation of swallowing dysfunction and of gastroesophageal reflux disease (GERD); and (V) minimization of vestibular and cochlear dysfunction associated with some anti-NTM drugs.ConclusionsWhile antibiotics is often the central focus of treatment of NTM-LD, given its propensity for recurrent and recalcitrant infection, other ancillary measures to break the vicious cycle of injurious inflammation and infection should also be emphasized to optimize treatment success.