Research Spotlight

Rasmussen, M., Leeds, S. G., Ward, M. A., Sanchez, C., Chin, K., Hansen, L. and Ogola, G. O. (2022). “Can subjective symptoms predict objective findings in gastroesophageal reflux disease patients?” Surg Endosc.

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INTRODUCTION: Medical therapy is the first-line treatment for gastroesophageal reflux disease, but surgical options are available and shown to be effective when medical management fails. There is no consensus for when a surgical evaluation is indicated. We set out to determine if the GERD-HRQL questionnaire scores correlate to objective findings found in patients undergoing anti-reflux surgery to predict when surgical consultation could be warranted. METHODS: A prospectively gathered database was used for patients undergoing anti-reflux surgery from January 2014 to September 2020. Inclusion criteria required a diagnosis of GERD and comprehensive esophageal workup with the GERD-HRQL questionnaire, EGD, esophageal manometry, and ambulatory pH monitoring. Analysis of the GERD-HRQL scores was compared to objective endpoints to see correlation and predictability. Logistic regression analysis was used to assess relationship between the presence of objective findings and GERD-HRQL questionnaire scores. RESULTS: There were 246 patients meeting inclusion criteria. There was no significant correlation between GERD-HRQL score and DeMeester score (correlation coefficient = 0.23), or presence of a hiatal hernia, regardless of size (p = 0.89). Patients with esophagitis had significantly higher average GERD-HRQL scores compared to those without esophagitis (40.1 ± 18.9 vs 30.4 ± 19.1, p < 0.0001). Patients with a score of 40 or greater had a 42% to 65% probability of having esophagitis versus a score of 30 or less, lowering the chances of having esophagitis to less than 35%. CONCLUSION: Usage of a GERD-HRQL questionnaire score can potentially show the correlation between subjective and objective findings in the workup of a patient for anti-reflux surgery. Specifically, patients with a GERD-HRQL score of 40 or greater have an increased probability of esophagitis compared to those with a score of 30 or less. Using these scores can help referring clinicians identify those patients failing medical therapy and allow for prompt referral for surgical evaluation.

Rabasco, A., McKay, D., Smits, J. A., Powers, M. B., Meuret, A. E. and McGrath, P. B. (2022). “Psychosocial treatment for panic disorder: An umbrella review of systematic reviews and meta-analyses.” J Anxiety Disord 86: 102528.

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BACKGROUND: Panic disorder is a common and disabling psychiatric condition marked by sudden onset of physiological sensations that are appraised as dangerous. A number of studies and reviews have examined the efficacy of psychosocial treatments for PD; however, there is a lack of overarching reports that discuss the strength of evidence for the different psychosocial treatments for PD. This umbrella review provides an overview of systematic reviews and meta-analyses on psychosocial treatments for PD. METHODS: A systematic search and review of the literature was conducted according to PRISMA guidelines. RESULTS: A total of 38 reviews (31 meta-analyses and 7 systematic reviews) were included in the umbrella review. Most of the 38 reviews were focused on the use of CBT, both in-person and internet-based, to treat PD among adults, generally finding it to be an efficacious treatment compared to control conditions. A limited number of the 38 reviews included other age ranges or examined other forms of psychosocial treatments. The methodological quality of most included reviews was rated as critically low according to the AMSTAR-2 rating system. CONCLUSIONS: Future reviews should focus on improving their methodological quality. Although the included reviews supported CBT as an efficacious treatment for reducing panic symptoms among adults, future research could focus on how CBT compares to other psychosocial treatments and the efficacy of CBT for PD among other populations (e.g., children and adolescents) and among diverse cultural groups.

Qin, T., Chen, K., Li, J., Qian, W., Xiao, Y., Wu, E., Ma, J., Chen, Z., Wang, Z., Ma, Q. and Wu, Z. (2022). “Heat shock factor 1 inhibition sensitizes pancreatic cancer to gemcitabine via the suppression of cancer stem cell-like properties.” Biomed Pharmacother 148: 112713.

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Pancreatic cancer is a fatal disease with poor prognosis. Gemcitabine has been regarded as the mainstay of chemotherapy for pancreatic cancer; however, it is accompanied with a high rate of chemoresistance. Cancer stem cells (CSCs) are characterized by resistance to traditional chemo- and radiotherapies. We have previously reported that heat shock factor 1 (HSF1) is involved in the invasion and metastasis of pancreatic cancer, a highly conserved transcriptional factor that mediates the canonical proteotoxic stress response. Here, we investigate whether HSF1 contributes to the chemoresistance of pancreatic cancer cells caused by gemcitabine and explore the underlying mechanisms. Genetically engineered mice (LSL-Kras(G12D/+); Trp53(fl/+); Pdx1-Cre mice), which spontaneously develop pancreatic cancer, were used to examine the sensitivity of pancreatic cancer to gemcitabine in vivo. We found that HSF1 was enriched in sphere-forming cancer cells. Panc-1 and MiaPaCa-2 cells treated chronically with gemcitabine displayed increased transcription and expression of CSC-associated markers. In addition, gemcitabine-surviving Panc-1 and MiaPaCa-2 cells showed an increased ability to form tumorspheres. Moreover, we observed that gemcitabine treatment increased the activity and expression of HSF1, as well as transcription of its downstream targets. Finally, HSF1 inhibition significantly suppressed the expression of CSC-associated markers, augmented the cancer-killing property of gemcitabine, and increased chemosensitivity to gemcitabine in vivo. Our study reveals a novel mechanism in which HSF1 promotes the chemoresistance of pancreatic cancer to gemcitabine by modulating CSC-like properties. Targeting HSF1 could be thus a rational strategy to improve treatment outcomes.

Polk, H., Johannesson, L., Testa, G. and Wall, A. E. (2022). “The Future of Uterus Transplantation: Cost, Regulations, and Outcomes.” Clin Obstet Gynecol 65(1): 101-107.

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Uterus transplantation (UTx) has evolved rapidly since technical success was first demonstrated, and is now practiced worldwide, using both living and deceased donors. As UTx transitions from an experimental to widely available standard clinical procedure, new challenges and questions are becoming more urgent. These include issues of cost and coverage, the establishment of guidelines and registries to ensure quality of care and monitor outcomes, regulatory oversight (including for the allocation organs from deceased donors), and the extent to which indications for UTx should be expanded.

Podduturi, V. and Guileyardo, J. M. (2022). “Methamphetamine Injection Into Face Causing Fatal Cavernous Sinus Thrombosis.” Am J Forensic Med Pathol.

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Cavernous sinus thrombosis is a rare and often fatal condition, usually associated with infections in the head and neck region. Clinical presentation includes fever, headache, and periorbital swelling. Mortality can be high; however, prompt treatment can reduce the probability of death. We present a case of a cavernous sinus thrombosis associated with methamphetamine injection into the face.