METHODS: A 62-year-old woman came to our hospital with worsening cough and dyspnea over the preceding week, during which time she had been treated with azithromycin and prednisone for suspected pneumonia. She had no fever, chills, or sweats, but her cough had become productive of clear to blood-tinged phlegm during the interval. Medical history was significant for insulin-dependent diabetes mellitus and OSA. She had quit smoking 44 years earlier and had no history of lung disease. She was a bank teller residing in southeastern Minnesota and described no relevant inhalational or environmental exposures, drug use, aspiration, or travels preceding her illness.

UNASSIGNED: Lower respiratory tract infection (LRTI) is a leading cause of infant morbidity and mortality globally. LRTI may be caused by viral or bacterial infections, individually or in combination. We investigated associations between LRTI and infant nasopharyngeal (NP) viruses and bacteria in a South African birth cohort.
UNASSIGNED: In a case-control study of infants enrolled in the Drakenstein Child Health Study (DCHS), LRTI cases were identified prospectively and age-matched with controls from the cohort. NP swabs were tested using quantitative real-time polymerase chain reaction (qPCR) and 16S rRNA gene amplicon sequencing. We calculated adjusted Conditional Odds Ratios (aORs) for qPCR targets and used mixed effects models to identify differentially abundant taxa between LRTI cases and controls and explore viral-bacterial interactions.
UNASSIGNED: Respiratory Syncytial Virus (RSV) [aOR: 5.69, 95% CI: 3.03-10.69], human rhinovirus (HRV) [1.47, 1.03-2.09], parainfluenza virus [3.46, 1.64-7.26], adenovirus [1.99, 1.08-3.68], enterovirus [2.32, 1.20-4.46], Haemophilus influenzae [1.72, 1.25-2.37], Klebsiella pneumoniae [2.66, 1.59-4.46], or high-density (> 6.9 log10 copies/mL) Streptococcus pneumoniae [1.53, 1.01-2.32] were associated with LRTI. Using 16S sequencing, LRTI was associated with increased relative abundance of Haemophilus (q = 0.0003) and decreased relative abundance of Dolosigranulum (q = 0.001), Corynebacterium (q = 0.091) and Neisseria (q = 0.004). In samples positive for RSV, Staphylococcus and Alloprevotella were present at lower relative abundance in cases than controls. In samples positive for parainfluenza virus or HRV, Haemophilus was present at higher relative abundance in cases.
UNASSIGNED: The associations between bacterial taxa and LRTI are strikingly similar to those identified in high-income countries, suggesting a conserved phenotype. RSV was the major virus associated with LRTI. H. influenzae appears to be the major bacterial driver of LRTI, acting synergistically with viruses. The Gram-positive bacteria Dolosigranulum and Corynebacteria may protect against LRTI, while Staphylococcus was associated with reduced risk of RSV-related LRTI.
UNASSIGNED: National Institutes of Health of the USA, Bill and Melinda Gates Foundation, National Research Foundation South Africa, South African Medical Research Council, L\'Oréal-UNESCO For Women in Science South Africa, Australian National Health and Medical Research Council.

BACKGROUND: Viral wheezing is an important risk factor for asthma, which comprises several respiratory phenotypes. We sought to understand if the etiology of early-life wheezing illnesses relates to childhood respiratory and asthma phenotypes.
METHODS: Data were collected prospectively on 429 children in the Urban Environment and Childhood Asthma (URECA) birth cohort study through age 10 years. We identified wheezing illnesses and the corresponding viral etiology (PCR testing of nasal mucus) during the first 3 years of life. Six phenotypes of respiratory health were identified at 10 years of age based on trajectories of wheezing, allergic sensitization, and lung function. We compared the etiology of early wheezing illnesses to these wheezing respiratory phenotypes and the development of asthma.
RESULTS: In the first 3 years of life, at least one virus was detected in 324 (67%) of the 483 wheezing episodes documented in the study cohort. Using hierarchical partitioning we found that non-viral wheezing episodes accounted for the greatest variance in asthma diagnosed at both 7 and 10 years of age (8.0% and 5.8% respectively). Rhinovirus wheezing illnesses explained the most variance in respiratory phenotype outcome followed by non-viral wheezing episodes (4.9% and 3.9% respectively) at 10 years of age.
CONCLUSIONS: Within this high-risk urban-residing cohort in early life, non-viral wheezing episodes were frequently identified and associated with asthma development. Though rhinovirus wheezing illnesses had the greatest association with phenotype outcome, the specific etiology of wheezing episodes in early life provided limited information about subsequent wheezing phenotypes.

OBJECTIVE: Our purpose was to assess the impact of muscle quality on overall survival (OS) in patients with advanced HCC.
METHODS: This is a subanalysis of the SORAMIC trial. Overall, 363 patients were included. The SIRT/Sorafenib treatment group comprised 182 patients and the sorafenib group 181 patients. Myosteatosis was defined as skeletal muscle density (SMD) < 41 HU for patients with a body mass index up to 24.9 kg/m2 and <33 HU for patients with a body mass index ≥25 kg/m2. Albumin-gauge score was calculated as follows: serum albumin (g/dL) × SMD (HU). To assess the impact of muscle quality on clinical variables and OS, a Cox regression model was used. Hazard ratios are presented together with 95 % confidence intervals (95 % CI). Kaplan-Meier curves were used for survival analysis.
RESULTS: In the SIRT/sorafenib cohort, low albumin-gauge score was an independent predictor of worse OS, HR = 1.74, CI 95% (1.16-2.62), p = 0.01. In the sorafenib cohort, muscle quality parameters did not predict OS. In alcohol-induced HCC (n = 129), myosteatosis independently predicted OS, HR = 1.85, CI 95% (1.10; 3.12), p = 0.02. In viral-induced HCC (n = 99), parameters of muscle quality did not predict OS. In patients with NASH/Non-alcoholic fatty liver disease (NAFLD) induced HCC, albumin-gauge score was a strong independent predictor of worse OS in the subgroup undergoing combined treatment with SIRT and sorafenib, HR = 9.86, CI 95% (1.12; 86.5), p = 0.04.
CONCLUSIONS: Myosteatosis predicts independently worse OS in patients with alcohol-induced HCC undergoing combined treatment with SIRT and sorafenib. In patients with NASH/NAFLD induced HCC undergoing treatment with SIRT and sorafenib, albumin-gauge score predicts independently worse OS.
UNASSIGNED: Associations between parameters of muscle quality and OS are different in accordance to the treatment strategy and etiology of HCC. These findings highlight the prognostic potential of skeletal muscle quality in patients with advanced HCC.

Hepatocellular carcinoma (HCC) is the most frequent among primary liver tumors (90%) and one of the main causes of cancer-related death. It develops usually in a chronically inflamed environment, ranging from compensatory parenchymal regeneration to fibrosis and cirrhosis: carcinogenesis can potentially happen in each of these stages. Inflammation determined by chronic viral infection (hepatitis B, hepatitis C, and hepatitis delta viruses) represents an important risk factor for HCC etiology through both viral direct damage and immune-related mechanisms. The deregulation of the physiological liver immunological network determined by viral infection can lead to carcinogenesis. The recent introduction of immunotherapy as the gold-standard first-line treatment for HCC highlights the role of the immune system and inflammation as a double-edged weapon in both HCC carcinogenesis and treatment. In this review we highlight how the inflammation is the key for the hepatocarcinogenesis in viral, alcohol and metabolic liver diseases.

BACKGROUND: The positive end-expiratory pressure (PEEP) strategy in patients with coronavirus 2019 (COVID-19) acute respiratory distress syndrome (ARDS) remains debated. Most studies originate from the initial waves of the pandemic. Here we aimed to assess the impact of high PEEP/low FiO2 ventilation on outcomes during the second wave in the Netherlands.
METHODS: Retrospective observational study of invasively ventilated COVID-19 patients during the second wave. Patients were categorized based on whether they received high PEEP or low PEEP ventilation according to the ARDS Network tables. The primary outcome was ICU mortality, and secondary outcomes included hospital and 90-day mortality, duration of ventilation and length of stay, and the occurrence of kidney injury. Propensity matching was performed to correct for factors with a known relationship to ICU mortality.
RESULTS: This analysis included 790 COVID-ARDS patients. At ICU discharge, 32 (22.5%) out of 142 high PEEP patients and 254 (39.2%) out of 848 low PEEP patients had died (HR 0.66 [0.46-0.96]; P = 0.03). High PEEP was linked to improved secondary outcomes. Matched analysis did not change findings.
CONCLUSIONS: High PEEP ventilation was associated with improved ICU survival in patients with COVID-ARDS.

BACKGROUND: In the conjugate vaccine era, viruses are the most common cause of meningitis. Here, we evaluated epidemiological trends in laboratory-confirmed viral meningitis across all age-groups over an 11-year period in England.
METHODS: In England, hospital laboratories routinely report laboratory-confirmed infections electronically to the UK Health Security Agency. Records of positive viral detections in cerebrospinal fluid during 2013-2023 were extracted. Incidence rates with confidence intervals were calculated using mid-year resident population estimates.
RESULTS: There were 22,114 laboratory-confirmed viral meningitis cases, including 15,299 cases during 2013-19 (pre COVID-19), with a gradual increase in incidence from 3.5/100,00 (95%CI: 3.3-3.6) to 3.9/100,000 (95%CI: 3.6-4.1). During 2020-21 when pandemic restrictions were in place, there were 2061 cases (1.8/100,000; 1.7-1.9), which increased to 4754 (4.2/100,000; 4.0-4.3) during 2022-23 (post pandemic restrictions). Infants aged <3 months accounted for 39.4% (8702/22,048) of all cases, with a stable incidence 2013-19 (504/100,000, 95%CI: 491-517), followed by a significant decline during 2020-21 (204/100,000; 188-221) and then an increase during 2022-23 (780/100,000; 749-812), with enteroviruses being the commonest cause (84.9%, 7387/8702; 424.74/100,000; 95%CI: 415.12-434.51), followed by parechoviruses (9.1%, 792/8702; 45.54/100,000; 95%CI: 42.42-48.82) and herpes simplex virus (4.4%, 380/8702; 21.85/100,000; 95%CI: 19.71-24.16). Pandemic restrictions were associated with significant declines in the incidence of enterovirus (77.7%) and parechoviruses (64% lower), with rebounds after societal restrictions were lifted.
CONCLUSIONS: Rates of viral meningitis have returned to pre-pandemic levels since societal restrictions were lifted. The highest incidence of viral meningitis remains in infants aged <3 months and most commonly due to enteroviral infection.

Emerging viruses pose significant threats to human health and the global economy. In the past two decades, three different coronaviruses have emerged to cause worldwide public health concerns. The advent of high throughput genomic and transcriptomic technologies facilitated the study of virus-host interactions, accelerating the development of diagnostics, vaccines, and therapeutics. Here, we describe quantitative PCR (qPCR) in studies of virus-host interactions to dissect host responses and viral kinetics and how these relate to one another.

In absence of a \"gold standard\", a standardized clinical adjudication process was developed for a registrational trial of a transcriptomic host response (HR) test. Two physicians independently reviewed clinical data to adjudicate presence and source of bacterial and viral infections in emergency department patients. Discordant cases were resolved by a third physician. Agreement among 955 cases was 74.1% (708/955) for bacterial, 75.6% (722/955) for viral infections, and 71.2% (680/955) overall. Most discordances were minor (85.2%; 409/480) versus moderate (11.7%; 56/480) or complete (3.3%; 16/480). Concordance levels were lowest for bacterial skin and soft tissue infections (8.2%) and for viral respiratory tract infections (4.5%). This robust adjudication process can be used to evaluate HR tests and other diagnostics by regulatory agencies and for educating clinicians, laboratorians, and clinical researchers. Clinicaltrials.gov NCT04094818. SUMMARY: Without a gold standard for evaluating host response tests, clinical adjudication is a robust reference standard that is essential to determine the true infection status in diagnostic registrational clinical studies.

UNASSIGNED: This study aimed to predict severe coronavirus disease 2019 (COVID-19) progression in patients with increased pneumonia lesions in the early days. A simplified nomogram was developed utilizing artificial intelligence (AI)-based quantified computed tomography (CT).
UNASSIGNED: From 17 December 2019 to 20 February 2020, a total of 246 patients were confirmed COVID-19 infected in Jingzhou Central Hospital, Hubei Province, China. Of these patients, 93 were mildly ill and had follow-up examinations in 7 days, and 61 of them had enlarged lesions on CT scans. We collected the neutrophil-to-lymphocyte ratio (NLR) and three quantitative CT features from two examinations within 7 days. The three quantitative CT features of pneumonia lesions, including ground-glass opacity volume (GV), semi-consolidation volume (SV), and consolidation volume (CV), were automatically calculated using AI. Additionally, the variation volumes of the lesions were also computed. Finally, a nomogram was developed using a multivariable logistic regression model. To simplify the model, we classified all the lesion volumes based on quartiles and curve fitting results.
UNASSIGNED: Among the 93 patients, 61 patients showed enlarged lesions on CT within 7 days, of whom 19 (31.1%) developed any severe illness. The multivariable logistic regression model included age, NLR on the second time, an increase in lesion volume, and changes in SV and CV in 7 days. The personalized prediction nomogram demonstrated strong discrimination in the sample, with an area under curve (AUC) and the receiver operating characteristic curve (ROC) of 0.961 and a 95% confidence interval (CI) of 0.917-1.000. Decision curve analysis illustrated that a nomogram based on quantitative AI was clinically useful.
UNASSIGNED: The integration of CT quantitative changes, NLR, and age in this model exhibits promising performance in predicting the progression to severe illness in COVID-19 patients with early-stage pneumonia lesions. This comprehensive approach holds the potential to assist clinical decision-making.