Research Spotlight

Lyon, K. A., J. H. Huang and D. Garrett (2020). “Influence of psychiatric disorders and chronic pain on the surgical outcome in the patient with chronic coccydynia: a single institution’s experience.” Neurol Res June 4; 1-6. [Epub ahead of print].

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OBJECTIVE: Performing coccygectomy procedures on patients with psychiatric disorders and/or chronic low back pain have been previously thought of as contributing factors leading to inconsistent and often poor results. To determine if these two variables affect the post-operative pain relief obtained after coccygectomy, an analysis of the opioid requirements and pain descriptions before and after surgery was undertaken in each patient studied. METHODS: The hospital electronic medical records were searched, and only patients undergoing coccygectomy for chronic coccydynia were selected. A total of 8 patients were found. Each patient underwent a trial of conservative therapy prior to surgical evaluation. RESULTS: The average duration of symptoms prior to surgery was 41.3 months. In 7 out of 8 patients, at least one psychiatric disorder was present. In 6 out of 8 patients, chronic low back pain was present. Pain control with opioid-based medicines was required in 5 out of 8 patients prior to surgery. Of those, 4 were able to discontinue or reduce the amount of opioid-based medicines consumed after surgery. The average follow-up was 9 months. DISCUSSION: The results of this study indicate that patients with preexisting psychiatric disorders and/or chronic low back pain suffering from debilitating coccyx pain can obtain pain relief after coccygectomy as seen from a reduction in opioid requirements and pain burden. It should be noted that the obtained benefits from coccygectomy usually occur in a delayed fashion.

Leeds, S. G., A. Ebrahim, E. M. Potter, J. S. Clothier, P. Prajapati, G. O. Ogola and M. A. Ward (2020). “The role of preoperative workup in predicting dysphagia, dilation, or explantation after magnetic sphincter augmentation.” Surg Endosc May 27. [Epub ahead of print].

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BACKGROUND: Magnetic sphincter augmentation (MSA) is a surgical treatment for gastroesophageal reflux disease using a ring of titanium beads to improve the function of the lower esophageal sphincter. Prior to implantation, a comprehensive preoperative esophageal workup is required to determine patient candidacy in an effort to reduce the dysphagia, dilation, and explantation rate of the device. This study was designed to assess the best predictors for these endpoints. METHODS: A prospectively maintained IRB-approved database was retrospectively reviewed for patients undergoing MSA implantation. Patients were divided into 3 groups, those that needed no intervention, those that needed medical intervention with oral steroids for reported dysphagia, and surgical intervention, which included endoscopic dilation and/or surgical explantation. Primary endpoints included preoperative objective and subjective testing from a comprehensive esophageal workup including intraoperative notation of number of beads on the device. RESULTS: There were 99 patients eligible for the study with a mean age of 52 and mean follow-up of 10.2 months. Mean BMI was 27 and 59% were female. The no-intervention group had 59 patients, medical intervention group had 25 patients, and surgical intervention group had 15 patients. Preoperative esophageal manometry findings, pH testing off medications, endoscopic and radiologic evaluation showed no difference between the 3 groups. No differences were seen in preoperative subjective evaluations based on GERD-HRQL or RSI scores. There was no difference in average number of beads on the device between the 3 groups. CONCLUSION: A comprehensive esophageal workup is important to confirm the presence of gastroesophageal reflux disease and rule out other esophageal pathology. However, this study shows that a preoperative comprehensive esophageal workup does not predict which patients will develop dysphagia or require either medical or surgical interventions following MSA implantation.

Kim, K. H., L. She, K. L. Lee, R. Dabrowski, P. A. Grayburn, M. Rajda, D. L. Prior, P. Desvigne-Nickens, W. A. Zoghbi, M. Senni, G. Stefanelli, C. Beghi, T. Huynh, E. J. Velazquez, J. K. Oh and G. Lin (2020). “Incremental prognostic value of echocardiography of left ventricular remodeling and diastolic function in STICH trial.” Cardiovasc Ultrasound 18(1): 17.

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AIMS: We sought to determine which echocardiographic markers of left ventricular (LV) remodeling and diastolic dysfunction can contribute as incremental and independent prognostic information in addition to current clinical risk markers of ischemic LV systolic dysfunction in the Surgical Treatment for Ischemic Heart Failure (STICH) trial. METHODS AND RESULTS: The cohort consisted of 1511 of 2136 patients in STICH for whom baseline transmitral Doppler (E/A ratio) could be measured by an echocardiographic core laboratory blinded to treatment and outcomes, and prognostic value of echocardiographic variables was determined by a Cox regression model. E/A ratio was the most significant predictor of mortality amongst diastolic variables with lowest mortality for E/A closest 0.8, although mortality was consistently low for E/A 0.6 to 1.0. Mortality increased for E/A < 0.6 and > 1.0 up to approximately 2.3, beyond which there was no further increase in risk. Larger LV end-systolic volume index (LVESVI) and E/A < 0.6 and > 1.0 had incremental negative effects on mortality when added to a clinical multivariable model, where creatinine, LVESVI, age, and E/A ratio accounted for 74% of the prognostic information for predicting risk. LVESVI and E/A ratio were stronger predictors of prognosis than New York Heart Association functional class, anemia, diabetes, history of atrial fibrillation, and stroke. CONCLUSIONS: Echocardiographic markers of advanced LV remodeling and diastolic dysfunction added incremental prognostic value to current clinical risk markers. LVESVI and E/A ratio outperformed other markers and should be considered as standard in assessing risks in ischemic heart failure. E/A closest to 0.8 was the most optimal filling pattern.

Kardashian, A., J. Ge, C. E. McCulloch, M. R. Kappus, M. A. Dunn, A. Duarte-Rojo, M. L. Volk, R. S. Rahimi, E. C. Verna, D. R. Ganger, D. Ladner, J. L. Dodge, B. Boyarsky, M. McAdams-DeMarco, D. L. Segev and J. C. Lai (2020). “Identifying an Optimal Liver Frailty Index Cutoff to Predict Waitlist Mortality in Liver Transplant Candidates.” Hepatology June 3. [Epub ahead of print].

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BACKGROUND & AIMS: Frailty, as measured by the liver frailty index (LFI), is associated with liver transplant (LT) waitlist mortality. We sought to identify an optimal LFI cutoff that predicts waitlist mortality. APPROACH&RESULTS: Adults with cirrhosis awaiting LT without hepatocellular carcinoma at 9 LT centers in the United States with LFI assessments were included. Multivariable competing risk analysis assessed the relationship between LFI and waitlist mortality. We identified a single LFI cutoff by evaluating the fit of the competing risk models, searching for the cutoff that gave the best model fit (as judged by the pseudo-log-likelihood). We ascertained the area under the curve (AUC) in an analysis of waitlist mortality to find optimal cutoffs at 3, 6, or 12 months. We used the AUC to compare the discriminative ability of LFI+Model for End Stage Liver Disease-sodium (MELDNa) versus MELDNa alone in 3-month waitlist mortality prediction. Of 1,405 patients, 37(3%), 82(6%), and 135(10%) experienced waitlist mortality at 3, 6, and 12 months, respectively. LFI was predictive of waitlist mortality across a broad LFI range: 3.7-5.2. We identified an optimal LFI cutoff of 4.4 (95%CI:4.0-4.8) for 3-month, 4.2 (95%CI:4.1-4.4) for 6-month, and 4.2 (95%CI:4.1-4.4) for 12-month mortality. The AUC for prediction of 3-month mortality for MELDNa was 0.73; the addition of LFI to MELDNa improved the AUC to 0.79. CONCLUSIONS: LFI is predictive of waitlist mortality across a wide spectrum of LFI values. The optimal LFI cutoff for waitlist mortality was 4.4 at 3 months and 4.2 at 6 and 12 months. The discriminative performance of LFI+MELDNa was greater than MELDNa alone. Our data suggest that incorporating LFI with MELDNa can more accurately represent waitlist mortality in LT candidates.

Kandimalla, R., T. Shimura, S. Mallik, F. Sonohara, S. Tsai, D. B. Evans, S. C. Kim, H. Baba, Y. Kodera, D. Von Hoff, X. Chen and A. Goel (2020). “Identification of Serum miRNA Signature and Establishment of a Nomogram for Risk Stratification in Patients With Pancreatic Ductal Adenocarcinoma.” Ann Surg May 8. [Epub ahead of print].

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OBJECTIVE: The aim of the study was to perform mRNA-miRNA regulatory network analyses to identify a miRNA panel for molecular subtype identification and stratification of high-risk patients with pancreatic ductal adenocarcinoma (PDAC). BACKGROUND: Recent transcriptional profiling effort in PDAC has led to the identification of molecular subtypes that associate with poor survival; however, their clinical significance for risk stratification in patients with PDAC has been challenging. METHODS: By performing a systematic analysis in The Cancer Genome Atlas and International Cancer Genome Consortium cohorts, we discovered a panel of miRNAs that associated with squamous and other poor molecular subtypes in PDAC. Subsequently, we used logistic regression analysis to develop models for risk stratification and Cox proportional hazard analysis to determine survival prediction probability of this signature in multiple cohorts of 433 patients with PDAC, including a tissue cohort (n = 199) and a preoperative serum cohort (n = 51). RESULTS: We identified a panel of 9 miRNAs that were significantly upregulated (miR-205-5p and -934) or downregulated (miR-192-5p, 194-5p, 194-3p, 215-5p, 375-3p, 552-3p, and 1251-5p) in PDAC molecular subtypes with poor survival [squamous, area under the receiver operating characteristic curve (AUC) = 0.90; basal, AUC = 0.89; and quasimesenchymal, AUC = 0.83]. The validation of this miRNA panel in a tissue clinical cohort was a significant predictor of overall survival (hazard ratio = 2.48, P < 0.0001), and this predictive accuracy improved further in a risk nomogram which included key clinicopathological factors. Finally, we were able to successfully translate this miRNA predictive signature into a liquid biopsy-based assay in preoperative serum specimens from PDAC patients (hazard ratio: 2.85, P = 0.02). CONCLUSION: We report a novel miRNA risk-stratification signature that can be used as a noninvasive assay for the identification of high-risk patients and potential disease monitoring in patients with PDAC.