Research Spotlight

Wang, C. H., W. T. Chang, C. H. Huang, M. S. Tsai, T. C. Lu, E. Chou, Y. W. Wu and W. J. Chen (2020). “Associations between Central Obesity and Outcomes of Adult In-hospital Cardiac Arrest: A Retrospective Cohort Study.” Sci Rep 10(1): 4604.

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To investigate the association between central obesity and outcomes following in-hospital cardiac arrest (IHCA). A single-centred retrospective study was conducted. Adult patients that experienced IHCA during 2006-2015 were screened. Body mass index (BMI) was calculated at hospital admission. Central obesity-related anthropometric parameters were measured by analysing computed tomography images. A total of 648 patients were included, with mean BMI of 23.0 kg/m(2). The proportions of BMI-defined obesity in this cohort were underweight (13.1%), normal weight (41.4%), overweight (31.5%) and obesity (14.0%). The mean waist circumference was 85.9 cm with mean waist-to-height ratio (WHtR) of 0.53. The mean sagittal abdominal diameter was 21.2 cm with mean anterior and posterior abdominal subcutaneous adipose tissue (SAT) depths of 1.6 and 2.0 cm, respectively. Multivariate logistic regression analyses indicated BMI of 11.7-23.3 kg/m(2) (odds ratio [OR]: 2.53, 95% confidence interval [CI]: 1.10-5.85; p-value = 0.03), WHtR of 0.49-0.59 (OR: 3.45, 95% CI: 1.56-7.65; p-value = 0.002) and anterior abdominal SAT depth <1.9 cm (OR: 2.84, 95% CI: 1.05-7.74; p-value = 0.04) were positively associated with the favourable neurological outcome. Central obesity was associated with poor IHCA outcomes, after adjusting for the effects of BMI.

Voss, R. K., J. C. Lin, M. T. Roper, M. H. Al-Temimi, J. H. Ruan, W. H. Tseng, M. Tam, M. J. Sherman, D. D. Klaristenfeld and M. J. Tomassi (2020). “Adjuvant Chemotherapy Does Not Improve Recurrence-Free Survival in Patients With Stage 2 or Stage 3 Rectal Cancer After Neoadjuvant Chemoradiotherapy and Total Mesorectal Excision.” Dis Colon Rectum 63(4): 427-440.

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BACKGROUND: Current guidelines for locally advanced stage 2/3 rectal cancer recommend neoadjuvant chemoradiotherapy followed by total mesorectal excision and adjuvant chemotherapy. The oncologic benefit of adjuvant chemotherapy has not been consistently demonstrated. OBJECTIVE: The purpose of this study was to evaluate disease recurrence and survival in patients with rectal cancer who received adjuvant chemotherapy after chemoradiotherapy and total mesorectal excision. DESIGN: This was a retrospective review of patients with stage 2/3 rectal cancer after chemoradiotherapy and surgery, based on receipt of adjuvant chemotherapy. SETTINGS: The study was conducted at the Kaiser Permanente Southern California system of 14 hospitals and associated clinics. PATIENTS: A total of 862 patients with stage 2/3 rectal cancer diagnosed and treated between January 1, 2005, and December 31, 2016, were included in this study. INTERVENTIONS: The study involved neoadjuvant chemoradiotherapy followed by total mesorectal excision with or without adjuvant chemotherapy. MAIN OUTCOME MEASURES: The primary end point was recurrence-free survival. RESULTS: A total of 348 stage 2 and 514 stage 3 patients were included; 660 patients (76.6%) underwent adjuvant chemotherapy. Mean patient follow-up after surgery was 63.0 months (range, 3-160). Multivariable analysis showed that yp stage (HR for yp stage 2 = 4.74; yp stage 3 = 8.83) and en bloc resection (HR = 1.76) were the only variables that significantly predicted disease recurrence. Neither pretreatment tumor stage nor receipt of adjuvant chemotherapy was significantly associated with recurrence-free survival. Log-rank testing failed to demonstrate significant recurrence-free survival improvement after receipt of adjuvant chemotherapy in any patient subgroup. LIMITATIONS: The study was limited by selection bias attributed to the nature of a retrospective study without patient randomization or predefined treatment protocol. CONCLUSIONS: In stage 2/3 rectal cancer treated with chemoradiotherapy and surgery, the addition of adjuvant chemotherapy was not associated with decreased recurrence-free survival in the entire cohort or in any subgroup, whereas tumor response to chemoradiotherapy is closely associated with disease recurrence. These findings have important consequences for treatment and surveillance decisions for patients with rectal cancer. Presurgical efforts that maximize tumor downstaging, such as total neoadjuvant therapy, may produce better oncologic outcomes than traditional adjuvant chemotherapy.

Van Der Pol, B., K. B. Waites, L. Xiao, S. N. Taylor, A. Rao, M. Nye, S. Chavoustie, A. Ermel, C. Kaplan, D. Eisenberg, P. A. Chan, L. Mena, S. Pacheco, S. Krishnamurthy, R. Mohan, R. Bertuzis, C. L. McGowin, R. Arcenas and E. M. Marlowe (2020). “Mycoplasma genitalium detection in urogenital specimens from symptomatic and asymptomatic men and women using the cobas TV/MG test.” J Clin Microbiol Mar 25. pii: JCM.02124-19. [Epub ahead of print].

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Mycoplasma genitalium (MG) infections are a growing concern within the field of sexually transmitted infections. However, diagnostic assays for MG have been limited in the United States (US). As most infections are asymptomatic, individuals can unknowingly pass the infection on and the prevalence is likely to be underestimated. Diagnosis of MG infection is recommended using a nucleic acid test. This multicenter study assessed the performance of the cobas(R) TV/MG assay (cobas) for the detection of MG, using 22,150 urogenital specimens from both symptomatic and asymptomatic men and women collected at geographically diverse sites across the US. The performance was compared to a reference standard of three laboratory-developed tests (LDTs). The specificity of the cobas assay for MG ranged from 96.0% to 99.8% across symptomatic and asymptomatic men and women. The sensitivity in female vaginal swabs and urine samples was 96.6% (95% confidence interval [CI] 88.5-99.1%) and 86.4% (95% CI 75.5-93.0%), respectively. The sensitivity in male urine and meatal swab samples was 100% (95% CI 94.0-100%) and 85.0% (95% CI 73.9-91.9%), respectively. This study demonstrated that the cobas assay was highly sensitive and specific in all relevant clinical samples for the detection of MG.

Spechler, S. J. (2020). “Refractory Gastroesophageal Reflux Disease and Functional Heartburn.” Gastrointest Endosc Clin N Am 30(2): 343-359.

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This report discusses the potential mechanisms that might underlie refractory GERD and functional heartburn, and how to distinguish among those mechanisms using a systematic evaluation that includes careful medical history, endoscopy with esophageal biopsy, esophageal manometry, and esophageal multichannel intraluminal impedance-pH monitoring. The report provides an approach to patient management that depends on the underlying mechanism identified by this systematic evaluation.

Singhal, N. K., S. Sternbach, S. Fleming, K. Alkhayer, J. Shelestak, D. Popescu, A. Weaver, R. Clements, B. Wasek, T. Bottiglieri, E. J. Freeman and J. McDonough (2020). “Betaine restores epigenetic control and supports neuronal mitochondria in the cuprizone mouse model of multiple sclerosis.” Epigenetics Mar 9:1-16. [Epub ahead of print].

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Methionine metabolism is dysregulated in multiple sclerosis (MS). The methyl donor betaine is depleted in the MS brain where it is linked to changes in levels of histone H3 trimethylated on lysine 4 (H3K4me3) and mitochondrial impairment. We investigated the effects of replacing this depleted betaine in the cuprizone mouse model of MS. Supplementation with betaine restored epigenetic control and alleviated neurological disability in cuprizone mice. Betaine increased the methylation potential (SAM/SAH ratio), levels of H3K4me3, enhanced neuronal respiration, and prevented axonal damage. We show that the methyl donor betaine and the betaine homocysteine methyltransferase (BHMT) enzyme can act in the nucleus to repair epigenetic control and activate neuroprotective transcriptional programmes. ChIP-seq data suggest that BHMT acts on chromatin to increase the SAM/SAH ratio and histone methyltransferase activity locally to increase H3K4me3 and activate gene expression that supports neuronal energetics. These data suggest that the methyl donor betaine may provide neuroprotection in MS where mitochondrial impairment damages axons and causes disability.