Analysis of the MLH1, MLH2, MLH6, PMS2 genes and their correlations with clinical data in rectal mucinous adenocarcinoma.

BACKGROUND: Microsatellites are short repeated DNA sequences normally found in the human genome. Following specific mutations, microsatellites can vary in the number of repeats thus making the DNA unstable. Microsatellite instability (MSI) is responsible for approximately 20% of rectal cancers, while the remaining 80% are caused by chromosomal instability. One of the following genes, MLH1, MLH2, MLH 6, and PMS2, is inactivated, leading to MSI colorectal cancers. AIM: This study aimed to analyze the expression of some MMR system genes presenting mutations in mucinous rectal cancer and their correlations with clinical data. METHODS: A retrospective study was performed on patients with rectal mucinous adenocarcinoma who underwent surgery between January 2000 and January 2017. We collected a total of 42 patients and analyzed the demographic data, histopathological results and MMR system genes mentioned above. RESULTS: Almost 93% of the cases analyzed had MSI-H and only 7% were MSI-L. For MLH1, 50% of stage T2 and 50% of stage T4 had weak expression, while in stage T3, 42.50% had moderate expression. Regarding the N stage, we found that 66.67% of the patients with moderate gene expression (2+) were N2, while 42% of the patients with weak expression were N0. For MSH2, the majority of patients with strong gene expression were in stage T3 (27%). Weak expression was found in 50% of the patients in stage T2, 35% of the patients in stage T3, and 33.3% in T4. In 44.44% of the weak expression was N2, while for strong expression, there was an equivalent percentage of 33.33% in stages N1 and N2. Describing the MSH6 gene, we found that the most heterogeneous results were in stage T3. Weak expression was observed in 38.46% of the patients, while moderate and strong expression was observed in 30.77% and 11.54% respectively. Analysis of PMS2 revealed that 66.67% of the patients in stage T4 had a weak expression of the gene, while the same expression was found in 38.46% of the patients in stage T3. A total of 23.08% of patients in stage T3 had strong gene expression. We also analyzed the overall gene expression. Thus, we found that three patients (7.14%) had only 1, three genes were expressed, nine (21.42%) had two genes and the remaining 27 patients had all 4. The 1-year survival rate in the analyzed lot was 75%, decreasing to 60% in the second year and 35% in the 3rd. There were no statistically significant differences in survival data between the stages or gene expression. CONCLUSIONS: Our study showed no statistical difference regarding the survival on different gene expression or staging, consistent with studies that found that mucin expression does not have a significant impact on local recurrence, nor does it affect nodal down staging. KEY WORDS: Mucinous adenocarcinoma, Microsatelites instability.

Evidence of a gabapentinoid and diuretic prescribing cascade among older adults with lower back pain.

BACKGROUND/OBJECTIVES: Gabapentinoids are commonly prescribed to relieve pain. The development of edema, an established adverse effect of gabapentinoids, may lead to a potentially harmful prescribing cascade whereby individuals are subsequently prescribed diuretics and exposed to diuretic-induced adverse events. The frequency of this prescribing cascade is unknown. Our objective was to measure the association between new dispensing of a gabapentinoid and the subsequent dispensing of a diuretic in older adults with new low back pain. DESIGN: Population-based cohort study. SETTING: Ontario, Canada. PARTICIPANTS: A total of 260,344 community-dwelling adults aged 66 years or older, newly diagnosed with low back pain between April 1, 2011, and March 31, 2019. MEASUREMENTS: Exposure status was assigned using dispensed medications in the 1 week after low back pain diagnosis. Older adults newly dispensed a gabapentinoid (N = 7867) were compared with older adults who were not newly dispensed a gabapentinoid (N = 252,477). Hazard ratios (HRs) with 95% confidence intervals (CIs) for dispensing of a diuretic within 90 days of follow-up among older adults prescribed gabapentin relative to those who were not. RESULTS: Older adults newly dispensed a gabapentinoid had a higher risk of being subsequently dispensed a diuretic within 90 days compared with older adults who were not prescribed a gabapentinoid (2.0% vs. 1.3%). After covariate adjustment, new gabapentinoid users had a higher rate of being dispensed a diuretic compared with those not prescribed a gabapentinoid (HR: 1.44, 95% CI: 1.23, 1.70). The rate of diuretic prescription among new gabapentinoid users increased with increasing gabapentinoid dosages. CONCLUSIONS: We have demonstrated the presence of a potentially inappropriate and harmful prescribing cascade. Given the widespread use of gabapentinoids, the population-based scale of this problem may be substantial. Increased awareness of this prescribing cascade is required to reduce the unnecessary use of diuretics and the exposure of patients to additional adverse drug events.

Health Forums and Twitter for Dementia Research: Opportunities and Considerations.

BACKGROUND/OBJECTIVES: Social media platforms are promising sources for large quantities of participant-driven research data and circumvent some common challenges when conducting dementia research. This study provides a summary of key considerations and recommendations about using these platforms as research tools for dementia. DESIGN: Mixed methods. SETTING: Alzheimer's Society's online Dementia Talking Point forum from inception to April 17, 2018, and Twitter in February and March 2018. PARTICIPANTS: All users of Dementia Talking Point who posted in subforums labeled "I have dementia" and "I care for a person with dementia," and Twitter users whose posts contained the keywords "dementia," "Alzheimer," or "Alzheimer's." MEASUREMENTS: We quantified the average daily number of dementia-related posts on each platform and number of words per post. Guided by a codebook, we conducted thematic content analysis of 5% of the 15,513 posts collected from Dementia Talking Point, and 10% of the 25,948 comprehensible posts from Twitter containing "dementia," "Alzheimer," or "Alzheimer's." We also summarized research-relevant characteristics inherent to platforms and posts. RESULTS: On average, Dementia Talking Point provided less than two new daily dementia-related posts with 213.5 to 241.5 words, compared with 7,883 new daily Twitter posts with 14.5 words. Persons with dementia (PWDs) commonly shared dementia-related concerns (75.7%), experiences (68.6%), and requests for, as well as offers of, information and support (44.3% and 38.6%, respectively). Caregivers commonly shared caregiving experience (67.0%) and requests for information and support (52.5%). Most common dementia-related Twitter posts were derogatory use of the term dementia (14.5%), advocacy, fundraising, and awareness (11.6%), and research dissemination (8.0%). Recommendations about these platforms' unique technical and ethical considerations are outlined. CONCLUSIONS: Understanding the priorities of PWDs and their caregivers remains important to understand how clinicians can best support them. This study will help clinicians and researcher to better leverage online health forums and Twitter for such dementia-related information.

Management of Sleep Disorders in Community-Dwelling Older Women and Men at the Time of Diagnosis.

OBJECTIVES: Sedative and hypnotic medications are associated with harm, and guidelines suggest limiting their use. Only limited evidence has described how older adults are managed following an initial sleep disorder diagnosis. We aimed to describe clinical management patterns of sleep disorders in older women and men at the time of initial diagnosis. DESIGN: Population-based retrospective cohort study using linked administrative databases. SETTING: Ontario, Canada. PARTICIPANTS: Community-dwelling adults aged 66 and older, diagnosed with a new sleep disorder by a primary care provider (n = 30 729; 56% women and 44% men). We compared women and men for each outcome. MEASUREMENTS: The primary outcome was prescription of a medication used for sleep within 30 days of a new sleep disorder diagnosis. Additional analysis included medical investigations such as sleep studies and visits to specialists who manage obstructive sleep disorders within 90 days of diagnosis. RESULTS: Among the 30 729 older adults with a new sleep disorder diagnosis, 5512 (17.9% total; 18.8% of women and 16.9% of men) were prescribed a medication used for sleep. Compared with men, women were somewhat more likely to be prescribed at least one sedative medication (adjusted odds ratio = 1.09; 95% confidence interval = 1.03-1.16). A total of 2573 (8.4%) older adults underwent a sleep study, and 3743 (12.2%) were evaluated by a specialist; both occurred more commonly in men. CONCLUSION: In our cohort, almost 1 in 5 older adults with a new sleep disorder diagnosis were prescribed a medication used for sleep; of these, a higher proportion were women. Comparatively few older adults were further evaluated; of these, a higher proportion were men. Our study highlights the high rates at which medications are prescribed to older adults with a new sleep disorder diagnosis and identifies potential sex differences in the management of such diagnoses. J Am Geriatr Soc 1-8, 2019. J Am Geriatr Soc 67:2094-2101, 2019.

Intravascular large B-cell lymphoma presenting as Richter's syndrome with cerebral involvement in a patient with chronic lymphocytic leukemia.

Intravascular large B-cell lymphoma (IVLBCL) is an aggressive non-Hodgkin's lymphoma which can present with B symptoms, rash, and neurological deterioration. Up to 10% of cases of IVLBCL are associated with other hematological neoplasms, including this extremely rare presentation of IVLBCL as Richter's transformation in chronic lymphocytic leukemia.