Mycobacterium tuberculosis (M. tuberculosis) causes an enormous burden of disease worldwide. As a central aspect of its pathogenesis, M. tuberculosis grows in macrophages, and host and microbe ...influence each other's metabolism. To define the metabolic impact of M. tuberculosis infection, we performed global metabolic profiling of M. tuberculosis-infected macrophages. M. tuberculosis induced metabolic hallmarks of inflammatory macrophages and a prominent signature of cholesterol metabolism. We found that infected macrophages accumulate cholestenone, a mycobacterial-derived, oxidized derivative of cholesterol. We demonstrated that the accumulation of cholestenone in infected macrophages depended on the M. tuberculosis enzyme 3β-hydroxysteroid dehydrogenase (3β-Hsd) and correlated with pathogen burden. Because cholestenone is not a substantial human metabolite, we hypothesized it might be diagnostic of M. tuberculosis infection in clinical samples. Indeed, in 2 geographically distinct cohorts, sputum cholestenone levels distinguished subjects with tuberculosis (TB) from TB-negative controls who presented with TB-like symptoms. We also found country-specific detection of cholestenone in plasma samples from M. tuberculosis-infected subjects. While cholestenone was previously thought to be an intermediate required for cholesterol degradation by M. tuberculosis, we found that M. tuberculosis can utilize cholesterol for growth without making cholestenone. Thus, the accumulation of cholestenone in clinical samples suggests it has an alternative role in pathogenesis and could be a clinically useful biomarker of TB infection.
Nontuberculous mycobacteria (NTM) infections are caused by environmental exposure. We describe spatial distribution of NTM infections and associations with sociodemographic factors and flooding in ...Missouri, USA. Our retrospective analysis of mycobacterial cultures reported to the Missouri Department of Health and Social Services surveillance system during January 1, 2008-December 31, 2019, detected geographic clusters of infection. Multilevel Poisson regression quantified small-area geographic variations and identified characteristics associated with risk for infection. Median county-level NTM infection rate was 66.33 (interquartile range 51-91)/100,000 persons. Risk of clustering was significantly higher in rural areas (rate ratio 2.82, 95% CI 1.90-4.19) and in counties with >5 floodings per year versus no flooding (rate ratio 1.38, 95% CI 1.26-1.52). Higher risk for NTM infection was associated with older age, rurality, and more flooding. Clinicians and public health professionals should be aware of increased risk for NTM infections, especially in similar environments.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Integrase inhibitors (INSTIs) have been associated with poorer cognition in people with HIV (PWH). We examined the impact of switching to INSTIs on neuropsychological (NP) outcomes in PWH 40 years of ...age and older.
From the AIDS Clinical Trials Group observational cohort study, HAILO, we identified PWH who switched to INSTIs, had ≥2 NP assessments before and at least 1 after switch, and maintained viral suppression while on INSTIs. NP performance was assessed with a composite score (NPZ4) including Hopkins Verbal Learning Test (HVLT-R), Digit Symbol test (DSY), Trail Making A, and Trail Making B, while adjusting for covariates and learning effects. Outcomes changes from preswitch and postswitch periods were estimated using piecewise linear mixed models.
Among 395 PWH (mean age 54 years, 81% male, 20% Hispanic, and 29% Black) NPZ4 increased preswitch and postswitch. There was no difference in slopes between periods for NPZ4 preswitch 0.036/year (95% CI: 0.03 to 0.043); postswitch 0.022/year (95% CI: 0.006 to 0.005); P = 0.147. All tests scores improved preswitch (P < 0.01). Postswitch, Trail Making A and DSY increased (all P < 0.01) without differences in rate of change (all P > 0.05). HVLT-R had a nonsignificant decrease postswitch (P = 0.22), resulting in a significant preswitch vs postswitch difference in slopes (P = 0.03).
NP performance improved regardless of INSTI use. There was an attenuation of improvement in verbal memory in the postswitch vs preswitch period. The clinical significance of these changes is unclear but, overall, INSTIs did not have a consistent detrimental effect on NP outcomes.
Although Worst pattern of invasion (WPOI) is one of the histopathological (HP) markers that has been utilized in risk stratification of oral squamous cell carcinoma (OSCC) patients, its potential as ...an independent predictive factor for lymph node metastasis (LNM) and prognosis is least analyzed. Aim of the study is to analyze the relationship of various HP parameters to WPOI, their propensity for lymph node metastasis and prognostic value. This retrospective study included 140 patients diagnosed with resectable OSCC who underwent definitive surgery. Multiparametric HP risk assessment was done on the postoperative specimen and patients were categorized as low-risk WPOI (Type 1–3), and high-risk group (type 4 and 5). After categorization, 36.1% patients had low-risk WPOI and 63.9% had high-risk WPOI. Significant association was noted between WPOI and patient’s age (p = 0.001), nodal stage (p = 0.001), lymphovascular invasion (LVI) (p = 0.006) and neural invasion (p = 0.001). 87% patients with nodal metastasis had high risk WPOI. LVI (p = 0.014) and WPOI (p < 0.001) had significant predictive role in LNM. High-risk WPOI and bone involvement were found to be predictive factors for overall survival, and only high risk WPOI had strong correlation with disease free survival having significant poor prognosis. Analyzing WPOI is essential in reporting HP specimens in OSCC. High-risk WPOI can act as an independent predictor for LNM, early recurrence and poor prognosis. Incorporation of WPOI into TNM staging is recommended to improve clinician’s ability to prognosticate and individualize treatment strategies.
In India, oral cancers are the major cause of cancer-related death. Tongue and buccal mucosa being the major subsites in oral cancer have varying clinicopathological presentations. This study is ...intended to know the difference in clinicopathological behavior of these two subsites. This retrospective study included 474 patients of which 232 patients had tongue cancer and 242 patients had buccal alveolar complex (BAC) cancer. Comparison between the pathological characters including pattern of nodal involvement was analyzed. Disease-free survival (DFS) and factors influencing the DFS were analyzed and compared using Cox regression analysis. Mean age of the study population was 52.7 years. Tongue oral squamous cell carcinoma (OSCC) differed significantly from BAC OSCC in terms of age of presentation, tumor staging, and perineural invasion. Among neck nodal involvement, tongue OSCC commonly involved level IIa (
p
< 0.001) whereas BAC involved level Ib (
p
< 0.001). At a median follow-up of 27 months, 141 patients had disease recurrence, tongue OSCC commonly recurred in neck (
p
= 0.008), and BAC OSCC relapsed at primary site (
p
= 0.001). Patients older than 45 years with BAC cancer had lesser risk of recurrence (HR, 0.30; 95% CI, 0.2–0.5;
p
< 0.0001). Pathological tumor stage in tongue cancer (HR, 14.9; 95% CI, 2.6–84.8;
p
= 0.002) and grade of tumor differentiation in BAC OSCC (HR, 9.2; 95% CI, 1.9–43.3;
p
< 0.005) were the most significant factors that influenced tumor recurrence. There was a significant difference in factors influencing disease recurrence among tongue and BAC OSCC. Also, pattern of nodal metastasis and pattern of recurrence were different. Hence, further research on OSCC may be done site specific.
Though work has been done studying nursing home (NH) residents with either advanced Alzheimer's disease (AD) or Alzheimer's disease related dementia (ADRD), none have distinguished between them; even ...though their clinical features affecting survival are different. In this study, we compared mortality risk factors and survival between NH residents with advanced AD and those with advanced ADRD.
This is a retrospective observational study, in which we examined a sample of 34,493 U.S. NH residents aged 65 and over in the Minimum Data Set (2011-2013). Incident assessment of advanced disease was defined as the first MDS assessment with severe cognitive impairment (Cognitive Functional Score equals to 4) and diagnoses of AD or ADRD. Demographics, functional limitations, and comorbidities were evaluated as mortality risk factors using Cox models. Survival was characterized with Kaplan-Maier functions.
Of those with advanced cognitive impairment, 35 % had AD and 65 % ADRD. At the incident assessment of advanced disease, those with AD had better health compared to those with ADRD. Mortality risk factors were similar between groups (shortness of breath, difficulties eating, substantial weight-loss, diabetes mellitus, heart failure, chronic obstructive pulmonary disease, and pneumonia; all p < 0.01). However, stroke and difficulty with transfer (for women) were significant mortality risk factors only for those with advanced AD. Urinary tract infection, and hypertension (for women) only were mortality risk factors for those with advanced ADRD. Median survival was significantly shorter for the advanced ADRD group (194 days) compared to the advanced AD group (300 days).
There were distinct mortality and survival patterns of NH residents with advanced AD and ADRD. This may help with care planning decisions regarding therapeutic and palliative care.
Highlights • Observed standard precaution adherence was suboptimal. • Sizeable discrepancy between reported and observed adherence exists. • Features of safety climate were correlated with standard ...precaution adherence.
Recently, the Centers for Medicare & Medicaid Services (CMS) final rule required that nursing homes (NHs) develop an infection control program that includes an antibiotic stewardship component and ...employs a trained infection preventionist (IP). The objectives of this study were to provide a baseline assessment of (1) NH facility and infection control program characteristics associated with having an infection control deficiency citation and (2) associations between IP training and the presence of antibiotic stewardship policies, controlling for NH characteristics. A cross-sectional survey of 2514 randomly sampled US NHs was conducted to assess IP training, staff turnover, and infection control program characteristics (ie, frequency of infection control committee meetings and the presence of 7 antibiotic stewardship policies). Responses were linked to concurrent Certification and Survey Provider Enhanced Reporting data, which contain information about NH facility characteristics and citations. Descriptive statistics and multivariable regression analyses were conducted to account for NH characteristics. Surveys were received from 990 NHs; 922 had complete data. One-third of NHs in this sample received an infection control deficiency citation. The NHs that received deficiency citations were more likely to have committees that met weekly/monthly versus quarterly (P < .01). The IPs in 39% of facilities had received specialized training. Less than 3% of trained IPs were certified in infection control. The NHs with trained IPs were more likely to have 5 of the 7 components of antibiotic stewardship in place (all P < .05). The IP training, although infrequent, was associated with the presence of antibiotic stewardship policies. Receiving an infection control citation was associated with more frequent infection control committee meetings. Training and support of IPs is needed to ensure infection control and antibiotic stewardship in NHs. As the CMS rule becomes implemented, more research is warranted. There is a need for increase in trained IPs in US NHs. These data can be used to evaluate the effectiveness of the CMS final rule on infection management processes in US NHs.
Oral cancers are the leading cause of cancer-related death in Indian men. Currently steps to contain the transmission and treatment of COVID-19 pandemic have crippled the entire health care system. ...With hospitals running short of resources, the oncological practice became standstill, especially during the initial phase. This is a retrospective study among patients who presented to our tertiary care hospital in early 3 months of COVID-19 era(ECE) with respect to pre-COVID-19 era(PCE). The study includes patients discussed in multidisciplinary tumor board(MDT)(421 in ECE Vs 31 in PCE) and those who underwent surgery(192 in ECE Vs 26 in PCE). The presentation and outcomes of oral carcinoma were compared between the two eras. There was a significant drop in the number of patients who presented during ECE. Though mean age and gender remained comparable between groups, there was a statistical difference in relation to demographic profile of patient (
p
value < 0.001). Among operated during ECE, 80% had a significantly advanced tumor stage (
p
value < 0.034) and advanced composite stage (
p
value < 0.049). Among patients discussed in MDT during ECE, 38.7% were deemed inoperable which is double the number when compared with PCE (
p
value < 0.009). Results of our study showed a higher incidence of advanced stage disease during ECE, with many patient turning inoperable. Thus, the survival of newly diagnosed oral carcinoma patients will be worser. In the management of oral cancer both early stage and advanced stage should have the same priority. Immediate resumption of safe oncology services is mandatory to curtail the current issues.
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