Publications by authors named "Richard Butterfield"

33 Publications

HIV Infection Is an Independent Predictor of Mortality Among Adults with Reduced Level of Consciousness in Uganda.

Am J Trop Med Hyg 2022 Jan 17. Epub 2022 Jan 17.

Department of Neurology, Mayo Clinic College of Medicine and Science, Phoenix, Arizona.

The clinical epidemiology of adults admitted with reduced level of consciousness (LOC) in sub-Saharan Africa (SSA) and the impact of HIV infection on the risk of mortality in this population is unknown. We secondarily analyzed data from a cohort study that enrolled 359 consecutive adults with reduced LOC presenting to Mbarara Regional Hospital in Uganda with the aim of comparing the prognostic utility of the Full Outline of Unresponsiveness (FOUR) score to the Glasgow Coma Scale (GCS) Score. For this analysis, we included 336 individuals with known HIV serostatus, obtaining clinical, laboratory, and follow-up data. We recorded investigations and treatments deemed critical by clinicians for patient care but were unavailable. We computed mortality rates and used logistic regression to determine predictors of 30-day mortality. The median GCS was 10. Persons living with HIV infection (PLWH) accounted for 97 of 336 (29%) of the cohort. The 30-day mortality rate in the total cohort was 148 of 329 (45%), and this was significantly higher in PLWH (57% versus 40%, adjusted odds ratio [aOR] 2.39: 95% confidence interval [CI]: 1.31-4.35, P = 0.0046). Other predictors of mortality were presence of any unmet clinical need (aOR 1.72; 95% CIL 1.04-2.84, P = 0.0346), anemia (aOR 1.68; 95% CI: 1.01-2.81, P = 0.047), and admission FOUR score < 12 [aOR 4.26; 95% CI: 2.36-7.7, P < 0.0001). Presentation with reduced LOC in Uganda is associated with high mortality rates, with worse outcomes in PLWH. Improvement of existing acute care services is likely to improve outcomes.
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http://dx.doi.org/10.4269/ajtmh.21-0813DOI Listing
January 2022

End-of-Life Care in Patients Undergoing Allogeneic Hematopoietic Cell Transplantation.

J Palliat Med 2022 Jan 27;25(1):97-105. Epub 2021 Oct 27.

Division of Hematology and Oncology, Mayo Clinic Arizona, Phoenix, Arizona, USA.

Patients receiving allogeneic hematopoietic cell transplantation (HCT) have high morbidity and mortality risk, but literature is limited on factors associated with end-of-life (EOL) care intensity. Describe EOL care in patients after allogeneic HCT and examine association of patient and clinical characteristics with intense EOL care. Retrospective chart review. A total of 113 patients who received allogeneic HCT at Mayo Clinic Arizona between 2013 and 2017 and died before November 2019. A composite EOL care intensity measure included five markers: (1) no hospice enrollment, (2) intensive care unit (ICU) stay in the last month, (3) hospitalization >14 days in last month, (4) chemotherapy use in the last two weeks, and (5) cardiopulmonary resuscitation, hemodialysis, or mechanical ventilation in the last week of life. Multivariable logistic regression modeling assessed associations of having ≥1 intensity marker with sociodemographic and disease characteristics, palliative care consultation, and advance directive documentation. Seventy-six percent of patients in our cohort had ≥1 intensity marker, with 43% receiving ICU care in the last month of life. Median hospital stay in the last month of life was 15 days. Sixty-five percent of patients died in hospice; median enrollment was 4 days. Patients with higher education were less likely to have ≥1 intensity marker (odds ratio 0.28,  = 0.02). Patients who died >100 days after HCT were less likely to have ≥1 intensity marker than patients who died ≤100 days of HCT ( = 0.04). Death within 100 days of HCT and lower educational attainment were associated with higher likelihood of intense EOL care.
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http://dx.doi.org/10.1089/jpm.2021.0093DOI Listing
January 2022

VO prior to transplant differentiates survival post kidney transplant.

Clin Transplant 2021 Oct 22:e14517. Epub 2021 Oct 22.

Division of Biomedical Statistics and Informatics, Mayo Clinic, Phoenix, Arizona, USA.

The OPTN/UNOS utilizes the calculated estimated posttransplant survival (EPTS) score as the measure of post-kidney transplant survival to guide allocation of deceased donor kidney transplantation. This score does not include any metric of functional capacity. Peak oxygen uptake (VO ), is an established predictor of survival among both the general and diseased populations. We assessed the association and discriminative capacity of VO and that of EPTS score and all-cause mortality post-kidney transplant. Additionally, we assessed the "mortality risk" lower VO conferred on those patients with low EPTS score. Among a cohort of 293 transplant recipients with at least 3-years post-transplant follow-up, the median VO was 15.0 ml/Kg/min. Lower pre-transplant VO and higher EPTS score conferred higher risk of post-transplant mortality. Among the cohort of "low-risk" patients (patients with EPTS score < 50) those with lower VO had significantly higher risk of mortality (log rank p = 0.045). In fact, the mortality risk among those with low-EPTS (< 50) and low VO < 12 ml/Kg/min was equivalent to those with high EPTS (> 80) score. We concluded functional capacity as defined by VO is an important reflection of post-transplant survival. VO is able to identify those with low EPTS who have similar survival to that of high EPTS phenotype.
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http://dx.doi.org/10.1111/ctr.14517DOI Listing
October 2021

Low-Dose Ketamine Infusion for Perioperative Pain Management in Patients Undergoing Laparoscopic Gastric Bypass: A Prospective Randomized Controlled Trial.

Anesthesiol Res Pract 2021 21;2021:5520517. Epub 2021 Jul 21.

Department of Anesthesiology and Perioperative Medicine, Mayo Clinic Hospital, 5777 E Mayo Blvd, Phoenix, AZ 85054, USA.

Introduction: Obesity is a common comorbidity seen in the perioperative setting and is associated with many diseases including cardiovascular disease and obstructive sleep apnea. Laparoscopic Roux-en-Y gastric bypass is the gold standard surgical treatment for patients whose weight is refractory to diet and exercise. Caring for these patients perioperatively presents unique challenges to anesthesiologists and is associated with an increased risk of adverse respiratory events. In our study, we hypothesize that a low-dose perioperative ketamine infusion will reduce opioid consumption and improve analgesia when compared to standard therapy.

Methods: This is a single-center, prospective randomized controlled study enrolling 35 patients in total. Patients were randomized equally into the ketamine and control group. Preop, intraop, and postop management regimens were standardized. The ketamine group received a 0.3 mg/kg ideal body weight ketamine bolus after induction followed by a 0.2 mg/kg/hr ketamine infusion continued into the postop setting for up to 24 hours. Data collected included total perioperative opioids used converted to oral morphine equivalents (ME), pain scores, side effects, hospital length of stay, and patient satisfaction captured via postoperative questionnaires.

Results: The use of perioperative opioid consumption was significantly lower in the ketamine group when compared with the control group (179.9 ME versus 248.7 ME, =0.03). There was no statistically significant difference in pain scores or hospital length of stay postoperatively between the two groups. There were also no reported adverse respiratory events, prolonged sedation, agitation, or other side effects reported in either group. The patient satisfaction questionnaires showed a significant difference with the ketamine group reporting lower maximum pain scores, a decrease in how pain limited activities of daily living once discharged, and increased hospital pain management satisfaction scores.

Conclusions: Perioperative low-dose ketamine infusions significantly reduced opioid consumption in morbidly obese patients undergoing laparoscopic gastric bypass surgery.
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http://dx.doi.org/10.1155/2021/5520517DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8321702PMC
July 2021

Differences in menopausal symptoms and female sexual function by region and ethnicity in West Texas and Central Arizona: a cross-sectional survey.

Menopause 2021 07 19;28(9):1037-1043. Epub 2021 Jul 19.

School of Medicine Greenville, University of South Carolina, Greenville, SC.

Objective: To evaluate menopausal symptoms and sexual problems in Hispanic and non-Hispanic women in two Southwest areas.

Methods: An anonymous survey including the Green Climacteric Scale (GCS), Female Sexual Function Index (FSFI), and demographics was distributed to English and Spanish-speaking women age 40 to 60 in Scottsdale, Arizona, and West Texas. FSFI for sexually active women and GCS scores for the Hispanic and non-Hispanic women in Texas were analyzed with multivariable analysis and compared between Texas and Arizona for Non-Hispanic participants.

Results: Predominantly non-Hispanic women (70%), average age 51.5 (SD = 7.25) completed questionnaires (199 West Texas, 163 Scottsdale). A majority of sexually active women (88%) were found to be at risk of sexual dysfunction. Within the Texas cohort, GCS score was estimated to be 3.49 points lower (less symptoms) in Hispanic versus non-Hispanic participants [95% CI -6.58 to -0.40, P = 0.03], and FSFI score was estimated to be 2.31 points lower (more symptoms) in Hispanic versus non-Hispanic participants [95% CI -4.49 to -0.14, P = 0.04]. Among non-Hispanic women, GCS scores were lower (less symptoms) in Texas versus Arizona by 10.25 points [95% CI -14.83 to -5.66, P < 0.01], while FSFI scores were higher overall (less symptoms) in Texas by 3.65 points [95% CI 0.53-6.77), P = 0.02]. All FSFI and GCS scores were adjusted for multiple variables.

Conclusions: In a group of menopausal women from the Southwest, most reported symptoms were consistent with FSD, and the degree of sexual problems appeared to be greater in the Hispanic participants from Texas.
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http://dx.doi.org/10.1097/GME.0000000000001810DOI Listing
July 2021

Prognostic Utility of Daily Changes in Glasgow Coma Scale and the Full Outline of Unresponsiveness Score Measurement in Patients with Metabolic Encephalopathy, Central Nervous System Infections and Stroke in Uganda.

Neurocrit Care 2021 Dec 23;35(3):835-844. Epub 2021 Jun 23.

Department of Neurology, Mayo Clinic, Phoenix, AZ, USA.

Background: Metabolic encephalopathy (ME), central nervous system (CNS) infections, and stroke are common causes of reduced level of consciousness in Uganda. However, the prognostic utility of changes in the daily measurements of the Full Outline of Unresponsiveness (FOUR) score and Glasgow Coma Scale (GCS) score in these specific disorders is not known.

Methods: We conducted secondary analyses of data from patients who presented with reduced level of consciousness due to CNS infections, stroke, or ME to a tertiary hospital in Uganda. Patients had FOUR/GCS scores at admission and at 24 and 48 h. We calculated a change in FOUR score (ΔFOUR) and change in GCS score (ΔGCS) at 24 and 48 h and used logistic regression models to determine whether these changes were predictive of 30-day mortality. In addition, we determined the prognostic utility of adding the admission score to the 24-h ΔFOUR and 24-h ΔGCS on mortality.

Results: We analyzed data from 230 patients (86 with ME, 79 with CNS infections, and 65 with stroke). The mean (SD) age was 50.8 (21.3) years, 27% (61 of 230) had HIV infection, and 62% (134 of 230) were peasant farmers. ΔFOUR at 24 h was predictive of mortality among those with ME (odds ratio [OR] 0.64 [95% confidence interval {CI} 0.48-0.84]; p = 0.001) and those with CNS infections (OR 0.65 [95% CI 0.48-0.87]; p = 0.004) but not in those with stroke (OR 1.0 [95% CI 0.73-1.38]; p = 0.998). However, ΔGCS at 24 h was only predictive of mortality in the ME group (OR 0.69 [95% CI 0.56-0.86]; p = 0.001) and not in the CNS or stroke group. This 24-h ΔGCS and ΔFOUR pattern was similar at 48 h in all subgroups. The addition of an admission score to either 24-h ΔFOUR or 24-h ΔGCS significantly improved the predictive ability of the scores in those with stroke and CNS infection but not in those with ME.

Conclusions: Twenty-four-hour and 48-h ΔFOUR and ΔGCS are predictive of mortality in Ugandan patients with CNS infections and ME but not in those with stroke. For individuals with stroke, the admission score plays a more significant predictive role that the change in scores.
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http://dx.doi.org/10.1007/s12028-021-01245-wDOI Listing
December 2021

Necrobiosis lipoidica-associated cutaneous malignancy.

J Am Acad Dermatol 2021 Jun 18. Epub 2021 Jun 18.

Department of Dermatology, Mayo Clinic, Scottsdale, Arizona. Electronic address:

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http://dx.doi.org/10.1016/j.jaad.2021.06.848DOI Listing
June 2021

Clinical and morphological features of necrobiosis lipoidica.

J Am Acad Dermatol 2021 Apr 18. Epub 2021 Apr 18.

Department of Dermatology, Mayo Clinic Arizona, Scottsdale, Arizona. Electronic address:

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http://dx.doi.org/10.1016/j.jaad.2021.04.034DOI Listing
April 2021

Evaluation of the Safety of Calcitonin Gene-Related Peptide Antagonists for Migraine Treatment Among Adults With Raynaud Phenomenon.

JAMA Netw Open 2021 04 1;4(4):e217934. Epub 2021 Apr 1.

Department of Dermatology, Mayo Clinic Arizona, Scottsdale.

Importance: Calcitonin gene-related peptide (CGRP) antagonists have demonstrated tremendous promise in migraine management. However, these medications decrease reflex vasodilatory response, which may lead to exacerbation of microvascular disease in susceptible patients, such as patients with Raynaud phenomenon (RP).

Objective: To investigate the microvascular complications of CGRP antagonists in patients with underlying RP.

Design, Setting, And Participants: This retrospective cohort study was performed from May 18, 2018, to September 15, 2020, in Mayo Clinic Health System patients with Raynaud phenomenon while undergoing CGRP antagonist therapy to treat migraine. Inclusion criteria were age older than 18 years, history of migraine, past or current treatment with CGRP antagonists, and diagnosis of primary or secondary RP.

Exposure: Treatment with CGRP antagonists.

Main Outcomes And Measures: The main outcome measure was microvascular complications (eg, worsening RP, digital ulcerations, and gangrenous necrosis) after initiation of treatment with a CGRP antagonist. Patient demographic and clinical characteristics were compared between those who experienced complications and those who did not.

Results: A total of 169 patients (163 [96.4%] female; 151 [89.3%] non-Hispanic White; mean [SD] age, 46 [13] years) were identified. Of the 169 patients, 9 (5.3%) exhibited microvascular complications, ranging from worsening RP to gangrene and autonecrosis that required distal digit amputation. Comparative analysis did not find statistically significant differences in demographic or clinical characteristics between the 2 cohorts. All 9 patients with complications were female (mean [SD] age, 40 [12] years). Five of the 9 patients (55.6%) had previously diagnosed RP; in 3 the RP was primary, and 2 it was secondary to scleroderma. The other 4 patients (44.4%) were newly diagnosed with RP. Eight of the 9 patients (88.9%) had chronic migraine; 4 had migraine with aura, and 5 had migraine without aura. The CGRP antagonist agents temporally associated with the microvascular complications included galcanezumab (in 3 patients), erenumab (in 5 patients), and fremanezumab (in 1 patient).

Conclusions And Relevance: The results of this study indicate that microvascular complications of CGRP antagonist use in patients with underlying RP are uncommon. The incidence of serious adverse events, although rare, warrant caution when considering the use of these agents in patients with RP.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.7934DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056280PMC
April 2021

Comorbidities and diabetic complications in patients with necrobiosis lipoidica.

J Am Acad Dermatol 2021 Mar 17. Epub 2021 Mar 17.

Department of Dermatology, Mayo Clinic Arizona, Scottsdale, Arizona. Electronic address:

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http://dx.doi.org/10.1016/j.jaad.2021.03.026DOI Listing
March 2021

A Framework for Revisiting Brain Death: Evaluating Awareness and Attitudes Toward the Neuroscientific and Ethical Debate Around the American Academy of Neurology Brain Death Criteria.

J Intensive Care Med 2021 Oct 22;36(10):1149-1166. Epub 2021 Feb 22.

Department of Biostatistics, Mayo Clinic, Scottsdale, AZ, USA.

Background: There remains a lack of awareness around the American Academy of Neurology (AAN) procedural criteria for brain death and the surrounding controversies, leading to significant practice variability. This survey study assessed for existing knowledge and attitude among healthcare professionals regarding procedural criteria and potential change after an educational intervention.

Methods: Healthcare professionals with increased exposure to brain injury at Mayo Clinic hospitals in Arizona and Florida were invited to complete an online survey consisting of 2 iterations of a 14-item questionnaire, taken before and after a 30-minute video educational intervention. The questionnaire gathered participants' opinion of (1) their knowledge of the AAN procedural criteria, (2) whether these criteria determine complete, irreversible cessation of brain function, and (3) on what concept of death they base the equivalence of brain death to biological death.

Results: Of the 928 people contacted, a total of 118 and 62 participants completed the pre-intervention and post-intervention questionnaire, respectively. The results show broad, unchanging support for the concept of brain death (86.8%) and that current criteria constitute best practice. While 64.9% agree further that the loss of consciousness and spontaneous breathing is sufficient for death, contradictorily, 37.6% believe the loss of additional integrated bodily functions such as fighting infection is necessary for death. A plurality trusts these criteria to demonstrate loss of brain function that is irreversible (67.6%) and complete (43.6%) at baseline, but there is significantly less agreement on both at post-intervention.

Conclusion: Although there is consistent support that AAN procedural criteria are best for clinical practice, results show a tenuous belief that these criteria determine irreversible and complete loss of all brain function. Despite support for the concept of brain death first developed by the President's Council, participants demonstrate confusion over whether the loss of consciousness and spontaneous breath are truly sufficient for death.
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http://dx.doi.org/10.1177/0885066620985827DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8442138PMC
October 2021

Effects of Intense Pulsed Light on Tear Film TGF-β and Microbiome in Ocular Rosacea with Dry Eye.

Clin Ophthalmol 2021 27;15:323-330. Epub 2021 Jan 27.

Ophthalmology, Mayo Clinic, Scottsdale, AZ, USA.

Purpose: To assess tear film transforming growth factor-beta (TGF-β) and ocular microbiome changes after intense pulsed light with meibomian gland expression (IPL-MGX) vs only MGX in treating ocular rosacea with dry eye symptoms.

Methods: Twenty patients were randomly assigned to IPL-MGX or MGX. Patients were examined, treated, and administered the ocular surface disease index (OSDI) survey every 4-6 weeks for four total treatments. Tear film and conjunctival samples were collected at first and last visits, and analyzed for TGF-β concentration and 16s rRNA amplicon sequencing of ocular microbiome. Wilcoxon Rank Sum and Sign-Rank were used to examine changes from baseline.

Results: OSDI revealed significantly greater improvement in symptoms after IPL-MGX (p=0.030) compared to MGX. There was no significant difference in mean TGF-β1, 2, or 3 concentration after IPL-MGX (p=0.385, 0.709, 0.948, respectively). Quantities of , , , , , , , , and were significantly reduced from baseline in both groups but without a significant difference between the two treatment groups.

Conclusion: IPL-MGX improved dry eye symptoms more than MGX alone. IPL treatment offered no additional benefit to MGX in decreasing virulent bacteria present on the ocular surface and did not influence TGF-β levels in tears. Prospective studies on IPL-MGX with larger sample sizes are needed to further investigate cytokines and IPL in patients suffering from ocular rosacea with dry eye symptoms.

Clinicaltrialsgov Identifier: NCT03194698.
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http://dx.doi.org/10.2147/OPTH.S280707DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7850425PMC
January 2021

Microvascular Transposition Without Teflon: A Single Institution's 17-Year Experience Treating Trigeminal Neuralgia.

Oper Neurosurg (Hagerstown) 2021 03;20(4):397-405

Department of Neurologic Surgery, Mayo Clinic, Phoenix, Arizona.

Background: Trigeminal neuralgia (TN) refractory to medical management is often treated with microvascular decompression (MVD) involving the intracranial placement of Teflon. The placement of Teflon is an effective treatment, but does apply distributed pressure to the nerve and has been associated with pain recurrence.

Objective: To report the rate of postoperative pain recurrence in TN patients who underwent MVD surgery using a transposition technique with fibrin glue without Teflon.

Methods: Patients were eligible for our study if they were diagnosed with TN, did not have multiple sclerosis, and had an offending vessel that was identified and transposed with fibrin glue at our institution. All eligible patients were given a follow-up survey. We used a Kaplan-Meier (KM) model to estimate overall pain recurrence.

Results: A total of 102 patients met inclusion criteria, of which 85 (83%) responded to our survey. Overall, 76 (89.4%) participants responded as having no pain recurrence. Approximately 1-yr pain-free KM estimates were 94.1% (n = 83), 5-yr pain-free KM estimates were 94.1% (n = 53), and 10-yr pain-free KM estimates were 83.0% (n = 23).

Conclusion: Treatment for TN with an MVD transposition technique using fibrin glue may avoid some cases of pain recurrence. The percentage of patients in our cohort who remained pain free at a maximum of 17 yr follow-up is on the high end of pain-free rates reported by MVD studies using Teflon. These results indicate that a transposition technique that emphasizes removing any compression near the trigeminal nerve root provides long-term pain-free rates for patients with TN.
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http://dx.doi.org/10.1093/ons/opaa413DOI Listing
March 2021

Evolving Natural History of Metastatic Prostate Cancer.

Cureus 2020 Nov 14;12(11):e11484. Epub 2020 Nov 14.

Hematology/Oncology, Mayo Clinic, Scottsdale, USA.

Introduction The systemic therapies available to patients with metastatic prostate cancer (mPC) have improved dramatically over the past decade. Anecdotal experience suggests that the increased available lines of therapy have changed the profile of mPC to include a higher prevalence of visceral metastases. Materials and Methods A retrospective review of 472 patients with prostate cancer who died in 2009 and in 2016 was performed. Patients with metastatic disease who had imaging within six months of death were included. A total of 164 patients were eligible for analysis. Results Overall rates of visceral and distant metastases, including the lung, liver, adrenal, brain, renal, spleen, and thyroid, were higher in patients who died in 2016 as compared to those who died in 2009 (40.0% and 26.1%, respectively, p-value = 0.07). Forty-four percent of patients who died in 2016 used five or more lines of systemic treatments compared to 26.1% of patients in 2009. Conclusion The emergence of new systemic therapies for mPC is changing the natural history of the disease. Visceral metastases are being seen with increasing frequency than in the past. This observation is important for clinicians who are monitoring patients with prostate cancer to maintain a high suspicion for visceral disease.
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http://dx.doi.org/10.7759/cureus.11484DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7735525PMC
November 2020

Migraine Treatment in Pregnancy: An American Headache Society Survey.

Headache 2020 11 29;60(10):2594-2596. Epub 2020 Sep 29.

Department of Neurology, Weill Cornell, New York, NY, USA.

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http://dx.doi.org/10.1111/head.13974DOI Listing
November 2020

Does location matter? Characterisation of the anatomic locations, molecular profiles, and clinical features of gliomas.

Neurol Neurochir Pol 2020 11;54(5):456-465. Epub 2020 Sep 11.

Mayo Clinic Arizona Department of Neurology.

Background: Neuroanatomic locations of gliomas may influence clinical presentations, molecular profiles, and patients' prognoses.

Methods: We investigated our institutional cancer registry to include patients with glioma over a 10-year period. Statistical tests were used to compare demographic, genetic, and clinical characteristics among patients with gliomas in different locations. Survival analysis methods were then used to assess associations between location and overall survival in the full cohort, as well as in relevant subgroups.

Results: 182 gliomas were identified. Of the tumours confined to a single lobe, there were 51 frontal (28.0%), 50 temporal (27.5%), 22 parietal (12.1%), and seven occipital tumours (3.8%) identified. Tumours affecting the temporal lobe were associated with reduced overall survival when compared to all other tumours (11 months vs. 13 months, log-rank p = 0.0068). In subgroup analyses, this result was significant for males [HR (95%CI) 2.05 (1.30, 3.24), p = 0.002], but not for females [HR (95%CI) 1.12 (0.65, 1.93), p = 0.691]. Out of 82 cases tested for IDH-1, 10 were mutated (5.5%). IDH-1 mutation was present in six frontal, two temporal, one thalamic, and one multifocal tumour. Out of 21 cases tested for 1p19q deletions, 12 were co-deleted, nine of which were frontal lobe tumours. MGMT methylation was assessed in 45 cases; 7/14 frontal tumours and 6/13 temporal tumours were methylated.

Conclusion: Our results support the hypothesis that the anatomical locations of gliomas influence patients' clinical courses. Temporal lobe tumours were associated with poorer survival, though this association appeared to be driven by these patients' more aggressive tumour profiles and higher risk baseline demographics. Independently, female patients who had temporal lobe tumours fared better than males. Molecular analysis was limited by the low prevalence of genetic testing in the study sample, highlighting the importance of capturing this information for all gliomas.

Importance Of This Study: The specific neuroanatomic location of tumours in the brain is thought to be predictive of treatment options and overall prognosis. Despite evidence for the clinical significance of this information, there is relatively little information available regarding the incidence and prevalence of tumours in the different anatomical regions of the brain. This study has more fully characterised tumour prevalence in different regions of the brain. Additionally, we have analysed how this information may affect tumours' molecular characteristics, treatment options offered to patients, and patients' overall survival. This information will be informative both in the clinical setting and in directing future research.
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http://dx.doi.org/10.5603/PJNNS.a2020.0067DOI Listing
November 2020

Current Practices for Screening and Management of Financial Distress at NCCN Member Institutions.

J Natl Compr Canc Netw 2020 07;18(7):825-831

3Fred Hutchinson Cancer Research Center, University of Washington Children's Hospital, Seattle, Washington.

Background: Financial distress from medical treatment is an increasing concern. Healthcare organizations may have different levels of organizational commitment, existing programs, and expected outcomes of screening and management of patient financial distress.

Patients And Methods: In November 2018, representatives from 17 (63%) of the 27 existing NCCN Member Institutions completed an online survey. The survey focused on screening and management practices for patient financial distress, perceived barriers in implementation, and leadership attitudes about such practices. Due to the lack of a validated questionnaire in this area, survey questions were generated after a comprehensive literature search and discussions among the study team, including NCCN Best Practices Committee representatives.

Results: Responses showed that 76% of centers routinely screened for financial distress, mostly with social worker assessment (94%), and that 56% screened patients multiple times. All centers offered programs to help with drug costs, meal or gas vouchers, and payment plans. Charity care was provided by 100% of the large centers (≥10,000 unique annual patients) but none of the small centers that responded (<10,000 unique annual patients; P=.008). Metrics to evaluate the impact of financial advocacy services included number of patients assisted, bad debt/charity write-offs, or patient satisfaction surveys. The effectiveness of institutional practices for screening and management of financial distress was reported as poor/very poor by 6% of respondents. Inadequate staffing and resources, limited budget, and lack of reimbursement were potential barriers in the provision of these services. A total of 94% agreed with the need for better integration of financial advocacy into oncology practice.

Conclusions: Three-fourths of NCCN Member Institutions reported screening and management programs for financial distress, although the actual practices and range of services vary. Information from this study can help centers benchmark their performance relative to similar programs and identify best practices in this area.
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http://dx.doi.org/10.6004/jnccn.2020.7538DOI Listing
July 2020

Clinical evaluation of fitness to drive in patients with brain metastases.

Neurooncol Pract 2019 Dec 3;6(6):484-489. Epub 2019 Jul 3.

Department of Neurology, Mayo Clinic, Phoenix, AZ.

Background: Guidelines to provide recommendations about driving restrictions for patients with brain metastases are lacking. We aim to determine whether clinical neurologic examination is sufficient to predict suitability to drive in these patients by comparison with an occupational therapy driving assessment (OTDA).

Methods: We prospectively evaluated the concordance between neurology assessment of suitability to drive (pass/fail) and OTDA in 41 individuals with brain metastases. Neuro-oncology evaluation included an interview and neurological examination. Participants subsequently underwent OTDA during which a battery of objective measures of visual, cognitive, and motor skills related to driving was administered.

Results: The mean age of patients who failed OTDA was age 68.9 years vs 59.3 years in the group members who passed ( = .0046). The sensitivity of the neurology assessment to predict driving fitness compared with OTDA was 16.1% and the specificity 90%. The 31 patients who failed OTDA were more likely to fail Vision Coach, Montreal Cognitive Assessment, and Trail Making B tests.

Conclusions: There was poor association between the assessment of suitability to drive by neurologists and the outcome of the OTDA in patients with brain metastases. Subtle deficits that may impair the ability to drive safely may not be evident on neurologic examination. The positive predictive value was high to predict OTDA failure. Age could be a factor affecting OTDA performance. The results raise questions about the choice of assessments in making recommendations about driving fitness in people with brain metastases. OTDA should be strongly considered in patients with brain metastases who wish to continue driving.
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http://dx.doi.org/10.1093/nop/npz027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6899051PMC
December 2019

Triptan and ergotamine overdoses in the United States: Analysis of the National Poison Data System.

Neurology 2020 04 2;94(14):e1460-e1469. Epub 2019 Dec 2.

From the Departments of Neurology (J.V.R., J.H.S.) and Biostatistics (R.J.B.), Mayo Clinic, Scottsdale; Departments of Child Health and Medicine, Division of Medical Toxicology and Precision Medicine (A.M.K.), University of Arizona College of Medicine-Phoenix; and Department of Medical Toxicology and Banner Poison and Drug Information Center (A.M.K.), Banner-University Medical Center Phoenix, AZ.

Objective: To examine the clinical outcomes of intentional overdoses involving triptans and ergotamines with a retrospective review of the National Poison Data System (NPDS).

Methods: This was a 5-year retrospective cross-sectional study (2014-2018) using the NPDS. Demographics, exposure characteristics, and outcomes were described. Univariate logistic regression was used to estimate the odds ratio (OR) for major effect or death. A multivariable logistic regression model with inclusion criteria of < 0.1 in univariate analysis was implemented with backwards selection.

Results: In this population (n = 1,489), multiple exposure was most common (n = 1,145). The mean age was 31.2 years and 1,197 (80.4%) participants were female. Major effects from a single exposure were seen in <1% with no recorded deaths. Triptan ingestion (n = 328) resulted in hypertension (14%), tachycardia (10.7%), drowsiness (11%), nausea (6.4%), vomiting (4.6%), vertigo (4%), chest pain (3.7%), and diaphoresis (2.4%). Ergotamine ingestion (n = 16) resulted in abdominal pain (16%), vomiting (12.5%), numbness (12.5%), nausea (6.3%), diarrhea (6.3%), and vertigo (6.3%). No clinical effect was seen in 90 (26.2%). No cases met Hunter criteria for serotonin syndrome. There is risk of major event or death due to age (OR 1.02; 95% confidence interval [CI] 1.01-1.04; = 0.004), multiple product exposure (OR 9.50; 95% CI 2.29-39.48; = 0.002), and concomitant overdose with benzodiazepines (OR 1.71; 95% CI 1.05-2.78; = 0.032) or tricyclic antidepressants (OR 3.16; 95% CI 1.88-5.31; < 0.001).

Conclusion: The risk of major effect or death was low and predicted by age, multiple product exposure, and concomitant benzodiazepine or tricyclic antidepressant. The triptan toxidrome consists of hypertension, tachycardia, and drowsiness. The toxic effects of ergotamine are acute gastrointestinal syndrome with vertigo and numbness. No cases of serotonin syndrome were seen.
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http://dx.doi.org/10.1212/WNL.0000000000008685DOI Listing
April 2020

Expanding the Spectrum of Radiation Necrosis After Stereotactic Radiosurgery (SRS) for Intracranial Metastases From Lung Cancer: A Retrospective Review.

Am J Clin Oncol 2020 02;43(2):128-132

Hematology/Oncology.

Objective: Radiation therapy (RT) is the primary treatment of intracranial metastasis (ICM) from lung cancer (LC). Radiation necrosis (RN) has been reported post-RT with an incidence of 5% to 24%. We reviewed the spectrum of imaging changes in patients treated with RT for ICM from LC in an effort to identify potential risk factors for RN.

Methods: We reviewed 63 patients with LC and ICM who received RT (radiosurgery [stereotactic radiosurgery] with/without whole brain radiation therapy) at our institution between 2013 and 2018. Data evaluated included demographics, tumor type, ICM burden and location, chemotherapy, surgery, and RT details as well as treatment choices and outcomes.

Results: Of the 63 patients, clinical and radiographic criteria for RN were noted in 24 (38%) as early as 2 months and as late as 5 years posttreatment. Six patients required surgical resection due to refractory symptoms revealing pathology-proven RN and occasionally tumor. Patients were significantly more likely to develop RN if they had surgical resection of an ICM (45.8% vs. 20.5%, P=0.05). No differences were found in location, size, or genetic profile of lesions. In total, 80% of patients received treatment for symptoms and/or radiographic change. This was generally a combination of steroids, bevacizumab, laser interstitial thermal treatment, or surgical resection. Most patients required >1 treatment modality.

Conclusions: This review of outcomes of RT for ICM in LC demonstrates a higher rate of RN than previously reported in the literature in those having had a surgical resection plus stereotactic radiosurgery. Our observation of RN as late as 5 years post-RT for ICM necessitates clinician awareness.
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http://dx.doi.org/10.1097/COC.0000000000000642DOI Listing
February 2020

Prognostic value of inositol polyphosphate-5-phosphatase expression in recurrent and metastatic cutaneous squamous cell carcinoma.

J Am Acad Dermatol 2020 Apr 19;82(4):846-853. Epub 2019 Aug 19.

Department of Dermatology, Mayo Clinic, Scottsdale, Arizona. Electronic address:

Background: Inositol polyphosphate-5-phosphatase (INPP5A) has been shown to play a role in the progression of actinic keratosis to cutaneous squamous cell carcinoma (cSCC) and the progression of localized disease to metastatic disease. Currently, no cSCC biomarkers are able to risk stratify recurrent and metastatic disease.

Objective: To determine the prognostic value of INPP5A expression in cSCC recurrent and metastatic disease.

Methods: We conducted a multicenter, single-institutional, retrospective cohort study within the Mayo Clinic Health System on the use of immunohistochemical staining to examine cSCC INPP5A protein expression in primary tumors and recurrent and metastatic disease. Dermatologists and dermatopathologists were blinded to outcome.

Results: Low staining expression of INPP5A in recurrent and metastatic disease tumors was associated with poor overall survival (OS) (31.0 months for low versus 62.0 months for high expression; P = .0272). A composite risk score (calculated as score of primary tumor + score of recurrent or metastatic disease tumor, with tumors with high expression scoring a zero and low expression a 1, score range 0-2) of 0 was predictive of improved OS compared with a composite risk score of ≥1 (hazard ratio 0.42, 95% confidence interval 0.21-0.84; P = .0113).

Limitations: This is a multicenter but single institution study of a white population.

Conclusion: Loss of INPP5A expression predicts poor OS in recurrent and metastatic disease of cSCC.
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http://dx.doi.org/10.1016/j.jaad.2019.08.027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7043906PMC
April 2020

A comparison of the Full Outline of Unresponsiveness (FOUR) and Glasgow Coma Scale (GCS) Scores in Predicting Mortality Among Patients with Reduced Level of Consciousness in Uganda.

Neurocrit Care 2020 06;32(3):734-741

Department of Neurology, Mayo Clinic, Phoenix, AZ, USA.

Background: Reduced level of consciousness (LOC) is a common cause of presentation among acutely ill adults in sub-Saharan Africa and is associated with high rates of mortality. Although the Full Outline of Unresponsiveness (FOUR) score is often used in clinical practice, its utility in predicting mortality has not been assessed in the region.

Methods: We prospectively enrolled adults presenting with reduced LOC to Mbarara Regional Referral Hospital in Uganda. We recorded clinical and laboratory data and performed the FOUR and Glasgow Coma Scale (GCS) scores at admission. We used survival analysis, fit Cox proportional hazards regression models to assess the predictive properties of the two scores, and compared their performance using area under the receiver operating characteristic curve (AUROC).

Results: We enrolled 359 patients, mean (SD) age was 51 (22.2) years, and 58% (210/359) were male. The median (interquartile range) admission FOUR and GCS scores were 13.0 (3.0-16.0) and 10.0 (3.0-14.0), respectively. Subjects with the FOUR score of 0-11 had a 2.6-fold higher hazard of 30-day mortality (HR 2.6, 95% CI 1.9-3.6, p < 0.001) compared to those with the score of 12-16. Those with the GCS score of 3-8 had a 2.7-fold higher hazard of 30-day mortality (HR 2.7, 95% CI 2.0-3.8, p < 0.001) compared to those with the score of 9-15. The AUROC (95% CI) for the FOUR score and GCS score was 0.68 (0.62-0.73) and 0.67 (0.62-0.73), respectively (p = 0.825).

Conclusions: The FOUR score is comparable to the GCS score in predicting mortality in Uganda. Our findings support the introduction of the FOUR score in guiding the management of patients with reduced LOC in sub-Saharan Africa.
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http://dx.doi.org/10.1007/s12028-019-00806-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7004860PMC
June 2020

CSF Pressure, Volume, and Post-Dural Puncture Headache: A Case-Control Study and Systematic Review.

Headache 2019 09 24;59(8):1324-1338. Epub 2019 Jul 24.

Department of Library Services, Mayo Clinic, Scottsdale, AZ, USA.

Objectives: (1) To perform a systematic literature review to evaluate associations between post-dural puncture headache (PDPH) and opening pressure (OP), closing pressure (CP), and volume of cerebrospinal fluid (V) removed. (2) To perform a case-control study to evaluate pressure-volume index (PVI) as a novel risk factor for PDPH.

Background: According to the International Classification of Headache Diagnoses, 3rd Edition (ICHD-3), the diagnosis of PDPH requires documentation of intracranial hypotension. However, this remains an unproven concept.

Methods: A systematic literature review was conducted, searching Cochrane Database of Systematic Reviews, Ovid EMBASE, OVID MEDLINE, Scopus, and Web of Science. Study inclusion required a comparison of headache incidence following a LP as a function of OP, CP, and/or V. A retrospective, case-control study with 1:1 matching was conducted utilizing ICHD-3 criteria. Patients with factors that could influence CSF pressure were excluded.

Results: In our case-control study, we did not identify a paired difference in either median (95% CI) elastance (0.05 [-0.09, 0.11], P = .503) or PVI (4.53 [-7.98, 19.97], P = .678). We identified 22 references, evaluating V (n = 14), OP (n = 11), and/or CP (n = 4). There was no convincing evidence for an association of PDPH with either OP or CP. A minority of studies documenting an association with V included patients with high-volume CSF removal, and/or stratified patients by the timing of the headache onset.

Conclusions: The overall risk of PDPH does not appear to be influenced by OP, CP, V or PVI. PDPH may be related to V in instances of high-volume removal, and depend on the timing of outcome assessment. Future revision of criteria should consider the existence of immediate and delayed PDPH subtypes, and not presume intracranial hypotension as a mandatory feature.
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http://dx.doi.org/10.1111/head.13602DOI Listing
September 2019

Assessment of Quality of Life following Allogeneic Stem Cell Transplant for Myelofibrosis.

Biol Blood Marrow Transplant 2019 11 6;25(11):2267-2273. Epub 2019 Jul 6.

Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Patient-reported outcomes (PROs) for patients with myelofibrosis (MF) have been well characterized, but little is known about quality of life (QoL) following allogeneic stem cell transplantation (allo-SCT). Medical data and PRO measures were collected before transplant and at day 30, day 100, and 1 year after allo-SCT. PRO measures include Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF), Brief Fatigue Inventory, Global Assessment of Change, and Functional Assessment of Cancer Therapy-Bone Marrow Transplant. Forty-four patients who had baseline QoL and at least 1 post-transplant assessment were included. The median age of the patients was 62.5 years (range, 35 to 74 years). At baseline, the mean MPN Total Symptom Score was 28.0, and at day 30, day 100, and 1 year, it was 25.4, 32.3, and 24.3, respectively. However, in myeloproliferative neoplasm-specific symptoms, such as itching, night sweats, bone pain, and fever, a statistically significant improvement was observed for at least 1 time point following transplant. At day 30, 10 (26.3%) patients reported a little/moderately/very much better overall QoL since their transplant, and 26 (68.45%) had a little/moderately/very much worse QoL. At day 100, 10 (30.3%) reported better QoL and 19 (57.6%) reported worsening since transplant. By 1 year, 16 (61.5%) reported feeling better. Our study shows that there is very little change in symptom burden at 1 year following transplant in general, but MF-specific symptoms showed improvement. By 1 year, 61% felt that their QoL was better than it was before transplant.
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http://dx.doi.org/10.1016/j.bbmt.2019.07.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8114229PMC
November 2019

Parameters associated with efficacy of epidural steroid injections in the management of postherpetic neuralgia: the Mayo Clinic experience.

J Pain Res 2019 23;12:1279-1286. Epub 2019 Apr 23.

Department of Dermatology, Mayo Clinic, Scottsdale, AZ, USA.

Thirty percent of patients with postherpetic neuralgia (PHN) receiving conservative treatment report unsatisfactory pain relief. Epidural steroid injections (ESIs) are commonly used as a therapeutic intervention in these patients. In this study, we aimed to determine if there are variables that predict the efficacy of ESI in patients with PHN. We retrospectively identified patients seen at Mayo Clinic who had PHN and received ESI. From their medical records, we abstracted the demographic variables, concurrent medication use, anatomic approach and medication for ESI, and degree of pain relief at 2 and 12 weeks' postintervention. None of the studied variables were significantly associated with efficacy of ESI in patients with PHN. PHN that began <11 months before treatment was predictive of a response to ESI at 12 weeks postintervention (positive predictive value, 55%). Patients who reported poor ESI efficacy 2 weeks after the intervention had a 94% chance of still having pain at 12 weeks. For this cohort of patients with PHN being treated with ESI, no demographic characteristics, concurrently used medications, or type of ESI were associated with ESI treatment efficacy at 2 or 12 weeks after the intervention.
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http://dx.doi.org/10.2147/JPR.S190646DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6503501PMC
April 2019

Radial artery access is under-utilized in women undergoing PCI despite potential benefits: Mayo Clinic PCI Registry.

Catheter Cardiovasc Interv 2020 03 21;95(4):675-683. Epub 2019 May 21.

Department of Cardiology, Mayo Clinic, Scottsdale, Arizona.

Background: Women may benefit from radial artery access (RAA) for percutaneous coronary interventions (PCI) due to a higher risk of bleeding compared to men; however, RAA may be underutilized in women. We sought to determine the frequency and predictors of RAA use in patients undergoing PCI.

Methods: We studied 21,123 (29.0% female) participants in the Mayo Clinic PCI Registry from January 1, 2006-December 31, 2016. Data were analyzed as a cohort and by time tertiles. Frequency of RAA versus femoral access and bleeding events were recorded. Logistic regression was used to identify predictors of RAA.

Results: In the overall cohort, women compared to men were older (69.6 ± 12.6 vs. 65.6 ± 11.9; p < .001), more likely to present with acute coronary syndrome (82.0% in women vs. 80.0% in men; p = .0008) and had more comorbidities. RAA increased from tertile one (3.5% for women vs. 4.0% for men; p = .3) through tertile three (46.8% for women vs. 50.3% for men; p = .01), but remained lower in women. In multivariable analysis, female sex is associated with 22% less RAA use (OR 0.78, 95% CI 0.72-0.84; p < .0001). Women compared to men experienced more bleeding (6.3 vs. 3.0%; p < .0001) but bleeding was less likely in RAA (OR 0.45, 95% CI 0.36-0.56; p < .0001).

Conclusion: Women undergoing PCI are less likely to receive RAA compared to men despite having a higher risk of bleeding. This trend persists despite increase in RAA use. Given the potential benefit of RAA in women, sex should be considered in patient selection for RAA.
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http://dx.doi.org/10.1002/ccd.28341DOI Listing
March 2020

Same-Day Discharge after Vaginal Hysterectomy with Pelvic Floor Reconstruction: Pilot Study.

J Minim Invasive Gynecol 2020 02 10;27(2):498-503.e1. Epub 2019 Apr 10.

Department of Gynecologic Surgery (Drs. Liu, Yi, Cornella, and Wasson). Electronic address:

Study Objective: To determine the safety and feasibility of same-day discharge (SDD) in patients undergoing vaginal hysterectomy with pelvic floor reconstruction.

Design: Prospective cohort pilot study.

Setting: Single academic medical center.

Patients: Women undergoing vaginal hysterectomy with pelvic floor reconstruction were considered for inclusion in the study.

Interventions: SDD or overnight hospitalization after surgery.

Measurements And Main Results: A total cohort of 55 women undergoing vaginal hysterectomy and pelvic floor reconstruction for pelvic organ prolapse and/or urinary incontinence was identified. The control group consisted of 19 women who were planned for overnight hospitalization. The intervention group had 36 women who were planned for SDD. In the intervention group 63.9% of patients (n = 23) were successfully discharged home and 36.1% (n = 13) required an unplanned overnight admission. Reasons for unplanned admission included persistent anesthetic effects (dizziness/nausea/drowsiness, n = 9, 69%), uncontrolled pain (n = 1, 7.7%), fever (n = 1, 7.7%), anemia (n = 2, 15.4%), with return to operating room for hematoma evacuation (n = 1, 7.7%). A voiding trial was passed on the first attempt in 30 patients (54.5%). The percentage of successful voiding trials on the first attempt was 30.8% for patients requiring unplanned admission and 78.9% for patients with planned overnight hospitalization (p = .011). There were no significant differences in the number of emergency department visits (p = .677) or unplanned office visits (p = .193) between the control and intervention groups.

Conclusion: SDD after vaginal hysterectomy with pelvic floor reconstruction appears to be safe and feasible. Patients who were discharged the same day did not require a higher volume of emergency department or office evaluations.
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http://dx.doi.org/10.1016/j.jmig.2019.04.010DOI Listing
February 2020

Germ Cell Tumors with Malignant Somatic Transformation: A Mayo Clinic Experience.

Oncol Res Treat 2019 27;42(3):95-100. Epub 2019 Feb 27.

Background: Germ cell tumors (GCTs) with malignant somatic transformation (MST) represent an uncommon variant of what is typically a curable malignancy. There is a paucity of data on time of somatic transformation, response to conventional therapy, and survival outcomes of different somatic subtypes.

Methods: After obtaining institutional review board (IRB) approval, we searched our institutional database from 1982 to 2017 and identified patients with GCTs with MST. Patient characteristics, pathologic description, treatment, and clinical outcomes were extracted from the medical records.

Results: We identified 24 cases of GCTs with MST; the MST was adenocarcinoma in 50% and sarcoma in 50%. Median age at diagnosis was 27. Alpha-fetoprotein and beta-human chorionic gonadotropin were undetectable in 44%, both were elevated in 54%. The majority were advanced stage (71% stage III), and International Germ Cell Cancer Collaborative Group (IGCCCG) risk was classified as 'good' in 60%. Median follow-up was 41 months (range 10-346 months). Median progression-free survival was 84 months (95% confidence interval (CI) 56-232), and median overall survival was 219 months (95% CI 165-not reported).

Conclusion: Patients with GCTs with an MST appear to have poor responses to cisplatin-based chemotherapy, suggesting that somatic component-driven therapies should be considered. Furthermore, resection of residual disease when feasible is an essential component of management.
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http://dx.doi.org/10.1159/000495802DOI Listing
August 2019
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