2 Minute Medicine Rewind December 3, 2023
1. This retrospective cohort study tested ovarian tumors for 113 viruses and found six viruses of interest (VOIs) that were present in one-quarter of tumors.
2. The presence of one of these VOIs was associated with a four-fold decrease in overall survival (OS) compared to those with any other viral strain or no viral strains. This finding did not apply to women above the age of 70, however.
Evidence Rating Level: 2 (Good)
Infectious agents are thought to cause just shy of one-fifth of cancer cases globally, and thus far, ovarian cancer is not known to have an infectious etiology. Internationally, eleven infectious organisms are currently classified as carcinogenic. However, one such infectious agent, human papillomavirus (HPV), is often found in ovarian tumors. The literature has not elucidated whether this takes place after the development of cancer or prior to it, but there is data to suggest that the expression of viral microRNA in tumors could be associated with worse clinical outcomes. Thus, this current study sought to assess whether ovarian tumors commonly carried viruses and whether presence of viruses in ovarian tumors was associated with decreased overall survival (OS). Tumor cells were analyzed from 98 patients (archived tumors) and any tissue that had been exposed to chemotherapies were excluded. The samples were tested by polymerase chain reaction (PCR) to detect 113 infectious agents. Results indicated that 46.9% of all samples contained at least one virus, and the most common viruses identified included herpesviruses EBV1 and HHV6b, polyomavirus MCPyV, a gamma HPV type (HPV4), a beta HPV types (HPV23), and one mucosal high-risk HPV (HPV16). In high-grade serous epithelial cancer, the most common histology of ovarian cancer, one or more of these six viruses of interest (VOI) were present in one quarter of tumors. Overall, patients with tumors containing any of these VOIs had a four-fold worse OS than those with other infectious agents or no virus present (HR 4.11, p = .0001; median survival 22 versus 44 months). This difference was no longer significant in women over the age of 70 (p > .05). Other factors also associated with lower OS included older age and advanced stage at diagnosis. Overall, these results indicate that viral infiltration of ovarian tumors may have implications for survival, but future studies should elucidate whether or not there is an element of reverse causation between these viruses and cancers.
1. This prospective cohort study revealed that children born to mothers with gestational diabetes mellitus (GDM) had significantly higher serum concentrations of branched-chain amino acids (BCAAs) at 6-year follow-up.
2. LDL levels were also significantly higher in offspring of GDM mothers at approximately 6 years of age.
Evidence Rating Level: 2 (Good)
The literature has established that children of mothers who experienced hyperglycemia at any point during pregnancy are at increased risk for cardiometabolic health issues and hypertension. However, the way by which this occurs is not well-studied. Some emerging literature suggests that maternal metabolomic profiles, which include amino acid (AA) concentrations, are altered in GDM and that these AA profiles also differ in offspring. AAs are also being studied in their relation to cardiovascular disease risk. The current study sought to investigate long-term impacts of GDM in mid-late pregnancy, hypothesizing that in these children, mid-childhood AA profiles and cardiometabolic risk would be increased. Women with GDM diagnosed between 26 and 28 weeks were recruited from two major hospitals between 2009 and 2010 as part of a larger study. Data were analyzed from 422 children at 6 years postpartum (mean age 6.1 years, 47.6% female). Significant differences in childhood leucine, valine and total BCAA levels were found between children of GDM and non-GDM mothers (p < .05). Children of mothers with higher fasting glucose at 26-28 weeks were more likely to have increases in plasma valine levels, and this was dose-dependent. Higher 26-28 week 2-hour glucose concentrations were associated with increased concentrations of histidine, leucine, valine, and total BCAAs in mid-childhood (ps < .05). From a cardiometabolic standpoint, the low-density lipoprotein (LDL) levels were significantly different between children of GDM and non-GDM mothers. AAs including isoleucine, leucine, valine, and total BCAAs demonstrated associations with mid-childhood cardiometabolic risks including insulin-resistance (HOMA-IR) and presence of high sensitivity C-reactive protein (hsCRP). Overall, the results of this study warrant further investigation before broad generalizations can be made, but this study does support one hypothesis for the mechanism by which GDM increases cardiometabolic risk.
1. In this superiority, parallel-group, open-label, multicentre, randomised controlled trial (RCT), point-of-care (POC) polymerase chain reaction (PCR) testing resulted in earlier use of targeted and adequate antibiotics, but did not result in less antibiotic use compared to the standard of care only (SCO).
Evidence Rating Level: 1 (Excellent)
With increasing rates of antimicrobial resistance worldwide, the topic of antibiotic stewardship is one of importance and developing efficient and effective ways to avoid antibiotic misuse and excessive use is pertinent. Community-acquired pneumonia (CAP) is a relatively common patient presentation which can have serious consequences if left untreated. Point-of-care (POC) polymerase chain reaction (PCR) testing presents a potential medium by which healthcare providers can more efficiently discontinue broad spectrum empiric antibiotics when not necessary and reduce the length of hospitalization. This method of testing has yet to be studied in the emergency department (ED) setting, which is exactly what the current study sought to do. The multicentre randomized study was conducted in three Danish hospitals and adults whose emergency physicians suspected CAP were invited to participate. Patients with suspected pneumonia (n = 291; median age 73, 51% male) were randomized 1:1 to either the POC-PCR group, or the standard care only (SCO) group. Those in the experimental group received results of POC-PCR from a sputum sample within 4 hours. POC-PCR was not found to be superior to SCO regarding prescriptions of ‘no or narrow-spectrum antibiotics’ within 4 hours of admission, and more patients in the SCO group were being treated with no or narrow spectrum treatments at the 5-day mark, which is likely due to the resulting of cultures. However, targeted and adequate antibiotics were used significantly more often in the POC-PCR group earlier on (both at 4 hours and 48 hours; p < .05), indicating that this method of testing can allow providers to make rapid, targeted decisions around antibiotic prescribing. There were no differences in mortality, admissions to ICU, or 30-day readmission between the groups. Length of stay was nonsignificant but was decreased for the POC-PCR group (4.3 vs 3.6 days, p = .164). The results of this study contradict some of the more promising findings of POC-PCR but should be replicated in environments where there is more resistance. There is also promise in the fact that targeted antibiotics were more efficiently selected when using POC-PCR in early stages of treatment.
Inflammatory Tongue Conditions and Risk of Oral Tongue Cancer Among the US Elderly Individuals
1. In this case-control study, those with tongue cancer were found to have ten-fold increases in rates of inflammatory tongue conditions (e.g., glossodynia, glossitis, precancer) preceding cancer diagnosis, and this remained significant even in conditions diagnosed ≥ 5 years prior to cancer occurrence.
2. Rates of oropharyngeal and oral cavity cancers were not found to be associated with tongue cancers.
Evidence Rating Level: 3 (Average)
Over the past decade alone, the rate at which people are being diagnosed with oral cancers, and specifically tongue cancer, is on the rise. It is well-established that certain modifiable risk factors increase risk for tongue cancer, including tobacco use, alcohol overuse, and HPV. There is also some literature to support that inflammatory states in the mouth may promote the development of tongue cancer. The current case-control study sought to investigate whether associations between certain inflammatory tongue conditions and oral cancer exist. The study population included patients with oral tongue, oral cavity, and oropharyngeal cancers (2,534, 6,832, and 9,373), as well as controls (200,000). Several inflammatory tongue conditions were included in the analysis of these patients’ medical records, including several types of glossitis, glossodynia, oral precancers, or other unspecified conditions. It was found that those with tongue cancers had significantly higher rates – ten-fold – of inflammatory conditions than healthy controls (6.0% and 0.6%, respectively; 95% CI, [4.7 to 7.2]), and this remained true even when inflammatory conditions had been diagnosed several years prior to the occurrence of the cancer (≥ five years). Oropharyngeal and other oral cancers were not found to be significantly associated with preceding inflammatory tongue conditions (p > .05). While these results are not absolute and bound to the limitations of a case-control study, there are some implications for the recognition of inflammatory tongue conditions as a risk factor for downstream oral cancers. Healthcare providers should potentially consider a heightened suspicion for oral precancers/cancers in patients with previous diagnosis of inflammatory tongue conditions, even spanning back ≥ 5 years.
1. Patients randomized to have Zinc (Zn) supplementation incorporated into an 8-week diet and exercise intervention for patients with NAFLD led to decreases in waist circumference, body-mass index (BMI), aspartate transaminase (AST), total cholesterol, and low-density lipoprotein (LDL-C) levels compared to controls.
Evidence Rating Level: 1 (Excellent)
Non-alcoholic fatty liver disease (NAFLD) is rising in prevalence globally and is currently the most common etiology of liver disease. Several modifiable risk factors are known to contribute to its development, and NAFLD predisposes patients to development of other chronic diseases such as diabetes and cardiovascular disease. While recommended treatment is usually lifestyle-related, the use of pharmacological agents may be beneficial. Zinc (Zn) deficiency in particular has been studied in relation to several metabolic conditions and is physiologically involved in the reduction of IR and oxidative stress, impacting other aspects of the lipid profile as well. The current randomized, double-blinded controlled clinical trial categorized 50 adults (mean age 44.68, SD 9.9 years) with NAFLD into either an intervention group (dietary plan + 30 mg Zinc gluconate daily) or control group (dietary plan + placebo capsule). After the 8-week study period, both groups experienced a significant change in weight from baseline (p < .05). However, in comparing intervention and control groups, the intervention group experienced a significant increase in Zn level, and decreases in weight, BMI, and waist circumference (ps < .05). There was also a significant change in AST, total cholesterol, and LDL-C levels (ps < .05) between the groups. However, no difference in IR, high-sensitivity C-reactive protein (hs-CRP), or high-density lipoprotein (HDL-C) levels was observed. The current study has its strengths in controlling diet for both intervention and control groups, which indicates that Zn could potentially serve useful in the treatment of NAFLD. Further studies are required to elucidate this finding, and should make use of a larger sample size to bolster validity of results.
Image: PD
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