Comparison of lung cancer occurring in fibrotic versus non-fibrotic lung on chest CT.

PURPOSE: Evaluate the behavior of lung nodules occurring in areas of pulmonary fibrosis and compare them to pulmonary nodules occurring in the non-fibrotic lung parenchyma. METHODS: This retrospective review of chest CT scans and electronic medical records received expedited IRB approval and a waiver of informed consent. 4500 consecutive patients with a chest CT scan report containing the word fibrosis or a specific type of fibrosis were identified using the system M*Model Catalyst (Maplewood, Minnesota, U.S.). The largest nodule was measured in the longest dimension and re-evaluated, in the same way, on the follow-up exam if multiple time points were available. The nodule doubling time was calculated. If the patient developed cancer, the histologic diagnosis was documented. RESULTS: Six hundred and nine patients were found to have at least one pulmonary nodule on either the first or the second CT scan. 274 of the largest pulmonary nodules were in the fibrotic tissue and 335 were in the non-fibrotic lung parenchyma. Pathology proven cancer was more common in nodules occurring in areas of pulmonary fibrosis compared to nodules occurring in areas of non-fibrotic lung (34% vs 15%, p < 0.01). Adenocarcinoma was the most common cell type in both groups but more frequent in cancers occurring in non-fibrotic tissue. In the non-fibrotic lung, 1 of 126 (0.8%) of nodules measuring 1 to 6 mm were cancer. In contrast, 5 of 49 (10.2%) of nodules in fibrosis measuring 1 to 6 mm represented biopsy-proven cancer (p < 0.01). The doubling time for squamous cell cancer was shorter in the fibrotic lung compared to non-fibrotic lung, however, the difference was not statistically significant (p = 0.24). 15 incident lung nodules on second CT obtained ≤ 18 months after first CT scan was found in fibrotic lung and eight (53%) were diagnosed as cancer. CONCLUSIONS: Nodules occurring in fibrotic lung tissue are more likely to be cancer than nodules in the nonfibrotic lung. Incident pulmonary nodules in pulmonary fibrosis have a high likelihood of being cancer.

Gut colonization with multidrug resistant organisms in the intensive care unit: a systematic review and meta-analysis.

BACKGROUND: Gut colonization with multidrug-resistant organisms (MDRO) frequently precedes infection among patients in the intensive care unit (ICU), although the dynamics of colonization are not completely understood. We performed a systematic review and meta-analysis of ICU studies which described the cumulative incidence and rates of MDRO gut acquisition. METHODS: We systematically searched PubMed, Embase, and Web of Science for studies published from 2010 to 2023 reporting on gut acquisition of MDRO in the ICU. MDRO were defined as multidrug resistant non-Pseudomonas Gram-negative bacteria (NP-GN), Pseudomonas spp., and vancomycin-resistant Enterococcus (VRE). We included observational studies which obtained perianal or rectal swabs at ICU admission (within 48 h) and at one or more subsequent timepoints. Our primary outcome was the incidence rate of gut acquisition of MDRO, defined as any MDRO newly detected after ICU admission (i.e., not present at baseline) for all patient-time at risk. The study was registered with PROSPERO, CRD42023481569. RESULTS: Of 482 studies initially identified, 14 studies with 37,305 patients met criteria for inclusion. The pooled incidence of gut acquisition of MDRO during ICU hospitalization was 5% (range: 1-43%) with a pooled incidence rate of 12.2 (95% CI 8.1-18.6) per 1000 patient-days. Median time to acquisition ranged from 4 to 26 days after ICU admission. Results were similar for NP-GN and Pseudomonas spp., with insufficient data to assess VRE. Among six studies which provided sufficient data to perform curve fitting, there was a quasi-linear increase in gut MDRO colonization of 1.41% per day which was stable through 30 days of ICU hospitalization (R2 = 0.50, p < 0.01). CONCLUSIONS: Acquisition of gut MDRO was common in the ICU and increases with days spent in ICU through 30 days of follow-up. These data may guide future interventions seeking to prevent gut acquisition of MDRO in the ICU.

Change in parental knowledge and beliefs about early childhood dental caries following a pragmatic community-based trial.

OBJECTIVES: To evaluate parent knowledge and belief changes following the MySmileBuddy (MSB) early childhood caries (ECC) intervention. METHODS: Pre- and post-intervention surveys were completed by 669 parents of children with visually-evident ECC from among 977 participants in a 6-12-month pragmatic community-based caries management trial administered by community health workers (CHWs). Six domains of knowledge about caries and motivating and facilitating determinants were assessed via 26 survey items. Principal components analysis and reliability testing reduced dataset dimensionality. Parent and CHW characteristics were analyzed as potential moderators. Paired T-tests measured pre-to-post-intervention changes. Generalized estimating equations accounted for within-participant correlation with significance set at p < 0.05. RESULTS: Twenty items consolidated into five factors (saliva, hygiene, diet, seriousness/susceptibility, and outcome expectations). Six additional items were evaluated individually. Positive post-intervention changes (p < 0.0001) were observed across all factors and all but one individual item (tooth decay is very common). Greatest knowledge increases related to caries as a bacterial disease in two measures, the saliva factor and a single caries belief item tooth decay is an infectious disease (0.59 unit increase, 95% CI [0.55, 0.64] and 0.46 unit increase, 95% CI [0.4, 0.51], respectively), and in the value of fluoridated water over bottled (0.46 unit increase, 95% CI [0.39-0.53]). Most parents improved knowledge of ECC salivary (72%) and dietary risks (57%), and preventative hygiene behaviors (59%). CONCLUSIONS: MSB enhanced knowledge and beliefs about caries and confirmed hypothesized mediators of behavior change among parents of high-risk children. Engaging peer-like CHW interventionists may have moderated intervention effects, warranting further exploration.

mTOR Inhibition Prolongs Survival and Has Beneficial Effects on Heart Function After Onset of Lamin A/C Gene Mutation Cardiomyopathy in Mice.

BACKGROUND: Mutations in LMNA encoding nuclear envelope proteins lamin A/C cause dilated cardiomyopathy. Activation of the AKT/mTOR (RAC-α serine/threonine-protein kinase/mammalian target of rapamycin) pathway is implicated as a potential pathophysiologic mechanism. The aim of this study was to assess whether pharmacological inhibition of mTOR signaling has beneficial effects on heart function and prolongs survival in a mouse model of the disease, after onset of heart failure. METHODS: We treated male LmnaH222P/H222P mice, after the onset of heart failure, with placebo or either of 2 orally bioavailable mTOR inhibitors: everolimus or NV-20494, a rapamycin analog highly selective against mTORC1. We examined left ventricular remodeling, and the cell biological, biochemical, and histopathologic features of cardiomyopathy, potential drug toxicity, and survival. RESULTS: Everolimus treatment (n=17) significantly reduced left ventricular dilatation and increased contractility on echocardiography, with a 7% (P=0.018) reduction in left ventricular end-diastolic diameter and a 39% (P=0.0159) increase fractional shortening compared with placebo (n=17) after 6 weeks of treatment. NV-20494 treatment (n=15) yielded similar but more modest and nonsignificant changes. Neither drug prevented the development of cardiac fibrosis. Drug treatment reactivated suppressed autophagy and inhibited mTORC1 signaling in the heart, although everolimus was more potent. With regards to drug toxicity, everolimus alone led to a modest degree of glucose intolerance during glucose challenge. Everolimus (n=20) and NV-20494 (n=20) significantly prolonged median survival in LmnaH222P/H222P mice, by 9% (P=0.0348) and 11% (P=0.0206), respectively, compared with placebo (n=20). CONCLUSIONS: These results suggest that mTOR inhibitors may be beneficial in patients with cardiomyopathy caused by LMNA mutations and that further study is warranted.

Reseña del estudio "LINKS": Factores asociados a la infección por VIH en hombres que tienen sexo con hombres de Buenos Aires, Argentina / Review of the "LINKS" study: Factors associated with HIV infection in men who have sex with men in Buenos Aires, Argentina

Este artículo resume resultados publicados del proyecto LINKS. Un to-tal de 500 hombres que tienen sexo con hombres se incluyeron en un estudio de factores asociados a la infección por VIH, utilizando la meto-dología de Muestreo Dirigido por los Participantes (Respondent Driven Sampling, RDS, en inglés). El 24,5 % se identificó como homosexual, 36,2 % como bisexual, 21,9 % como heterosexual y 17,4 % como "otro". El 33 % de los participantes reportó haber tenido relaciones sexuales con hombres, mujeres y mujeres trans durante los 2 meses previos. La prevalencia de VIH, hepatitis B y sífilis fue de 17,3 %, 22,9 % y 20,5 %, respectivamente. Los participantes que sólo reportaron parejas sexua-les masculinas tuvieron prevalencias significativamente mayores. Más de dos tercios reportaron coito anal o vaginal sin protección durante los últimos dos meses. El 52 % nunca se había realizado el diagnóstico de VIH. El 25 % informó consumo ex-cesivo de alcohol y 34 % poli-consumo de drogas du-rante los dos meses previos. El 18 % de participantes reportó una experiencia sexual antes de los 13 años con una pareja al menos cuatro años mayor de edad. La aceptabilidad de los microbicidas y de la prueba casera del VIH fue alta