Thyroid Cancer Incidence and Tumor Size in New Mexico American Indians, Hispanics, and Non-Hispanic Whites, 1992 to 2019.

BACKGROUND: The incidence of thyroid cancer in the United States has risen dramatically since the 1970s, driven by an increase in the diagnosis of small tumors. There is a paucity of published New Mexico (NM) specific data regarding thyroid cancer. We hypothesized that due to New Mexico's unique geographic and cultural makeup, the incidence of thyroid cancer and tumor size at diagnosis in this state would differ from that demonstrated on a national level. METHODS: The New Mexico Tumor Registry (NMTR) was queried to include all NM residents diagnosed with thyroid cancer between 1992 and 2019. For 2010 to 2019, age-adjusted incidence rates were calculated via direct method using the 2000 United States population as the adjustment standard. Differences in incidence rate and tumor size by race/ethnicity and residence (metropolitan vs non-metropolitan) were assessed with rate ratios between groups. For 1992 to 2019, temporal trends in age-adjusted incidence rates for major race/ethnic groups in NM [Non-Hispanic White (NHW), Hispanic, and American Indian (AI)] were assessed by joinpoint regression using National Cancer Institute software. RESULTS: Our study included 3,161 patients for the time period 2010 to 2019, including NHW (1518), Hispanic (1425), and AI (218) cases. The overall incidence rates for NM AIs were lower than those for Hispanics and NHWs because of a decreased incidence of very small tumors (<1.1 cm). The incidence rates for large tumors (>5.1 cm) was equivalent among groups. In the early 2000s, Hispanics also had lower rates of small tumors when compared to NHWs but this trend disappeared over time. CONCLUSION: AIs in New Mexico have been left out of the nationwide increase in incidental diagnosis of small thyroid tumors. This same pattern was noted for Hispanics in the early 2000s but changed over time to mirror incidence rates for NHWs. These data are illustrative of the health care disparities that exist among New Mexico's population and how these disparities have changed over time.

Surgeon and medical student response to patient death.

BACKGROUND: Virtually all surgeons will experience patient death in their practice. Despite this, little is known about how surgeons cope with patient death or its potential adverse impact on surgeons' well-being. Education on how to respond to loss is not often incorporated into current wellness curricula in surgical training. In light of the ongoing COVID-19 pandemic and the significant hospital-related mortality, understanding surgical provider response to patient loss takes on unique import. METHODS: A retrospective analysis was performed following administration of a 10-item survey that assessed healthcare provider (HCP) experience with patient death, activities used to cope with patient loss, and symptoms HCPs experienced. Participants included surgical faculty, residents, surgical advance practice providers and medical students on their surgical clerkship. Demographic characteristics were recorded: age, gender, academic level. Chi-squared test or Fisher exact test compared proportionality between those that did and did not experience patient loss. Logistic regression generated odds ratios examining impact of patient loss on symptoms experienced and activities engaged in after patient loss. RESULTS: Fifty-six (75%) respondents experienced patient death. Common responses were to talk with colleagues (71%) and seek comfort from family/friends/partner (55%). Most respondents did not report symptoms related to patient death (53%); burnout was the most common symptom reported (36%). Respondents were less likely to seek interpersonal support for COVID-19-related death (P<0.008). Only 49% of participants received education on coping with patient death. CONCLUSIONS: Few surgeons receive training related to patient death. Optimal coping strategies are unknown but may mitigate potential negative impacts, including burnout. The data presented here also suggests the need to establish medical education designed to mitigate the distress associated with patient loss.

Outcomes of Carotid Body Tumor Management with Active Surveillance.

OBJECTIVES: To assess outcomes of carotid body tumors (CBTs) managed with active surveillance. METHODS: Retrospective chart review of CBTs managed with active surveillance from 2001 to 2019. RESULTS: A total of 115 cases were identified during chart review. Sixty-five of these patients were managed with active surveillance, and 11 patients had bilateral tumors for a total of 76 tumors. Follow-up records with symptomatic outcomes were available for 51 patients, and 47 tumors had follow-up imaging. Thirty-one (66%) actively surveilled CBTs remained stable or decreased in size while 16 (34%) increased in size. Patients undergoing active surveillance developed symptoms in 12 cases, 6 of these patients underwent surgical intervention. Nine CBTs managed with active surveillance (18%) were ultimately resected. The majority of patients who did not undergo surgical intervention never developed symptoms (36/42, 86%). CONCLUSIONS: Active surveillance may be a reasonable approach for a subset of CBTs.

Tracheotomy in ventilator-dependent patients with COVID-19: a cross-sectional study of analgesia and sedative requirements.

OBJECTIVE: During March 2020 in the United States, demand for sedatives increased by 91%, that for analgesics rose by 79%, and demand for neuromuscular blockers increased by 105%, all owing to the number of COVID-19 cases requiring invasive mechanical ventilation (MV). We hypothesize that analgesic and sedative requirements decrease following tracheotomy in this patient population. METHODS: In this cross-sectional study, we conducted a retrospective chart review to identify patients with COVID-19 who underwent tracheotomy (T) at an academic medical center between March 2020 and January 2021. We used a paired Student t-test to compare total oral morphine equivalents (OMEs), total lorazepam equivalents, 24-hour average dexmedetomidine dosage in µg/kg/hour, and 24-hour average propofol dosage in µg/kg/minute on days T-1 and T+2 for each patient. RESULTS: Of 50 patients, 46 required opioids before and after tracheotomy (mean decrease of 49.4 mg OMEs). Eight patients required benzodiazepine infusion (mean decrease of 45.1 mg lorazepam equivalents. Fifteen patients required dexmedetomidine infusion (mean decrease 0.34 µg/kg/hour). Seventeen patients required propofol (mean decrease 20.5 µg/kg/minute). CONCLUSIONS: When appropriate personal protective equipment is available, use of tracheotomy in patients with COVID-19 who require MV may help to conserve medication supplies in times of extreme shortages.

Laparoscopic Revision of Nissen to Partial Fundoplication 20 Years After Initial Surgery as an Infant.

We report a case of a 21-year-old male who presented with adult-onset dysphagia after previous Nissen fundoplication initially created at age 10.5 months. The patient first presented one year ago to a different hospital, where he underwent extensive workup for his symptomatology. Physiologic tests performed were esophagogastroduodenoscopy (EGD), abdominal ultrasound, hepatobiliary iminodiacetic acid scan, esophageal manometry, and lactulose breath test. The EGD identified stricture at the level of the gastroesophageal junction. The other studies did not reveal other physiologic causes for his symptoms. The patient then presented to our institution, at which time a repeat EGD showed evidence of tight Nissen fundoplication. The patient subsequently underwent laparoscopic exploration, which revealed that the fundoplication had was partially disrupted, herniated, and twisted causing a long-segment distal stricture. To alleviate the patient's presenting symptom of dysphagia as well as prevent possible future reflux, it was decided to convert repair the hernia and revise the Nissen into a partial fundoplication. This was successfully accomplished laparoscopically with subsequent resolution of the patient's symptoms.

Distinct, sex-dependent miRNA signatures in piglet hippocampus induced by a clinically relevant isoflurane exposure: a pilot study.

PURPOSE: To evaluate the effects of sex on miRNA expression in the hippocampus after isoflurane anesthesia in a neonatal piglet model. METHODS: Six male and 6 female piglets, aged 3-5 days, were anesthetized with 2% isoflurane in room air for 3 h. Full physiologic monitoring was observed. Untreated animals (6 male, 6 female) served as controls. Expression of miRNAs in hippocampus was assessed. RESULTS: In controls, miRNA expression in the hippocampus was highly conserved between males and females. However, 17/326 displayed sex-dependent differences: 10 miRNAs were more highly expressed in males; 7 showed lower expression in males than females. Isoflurane was associated with changes in the expression of distinct subsets of miRNAs in both males and females. In females, 14/326 miRNAs were significantly changed (3 downregulated; 11 upregulated); in males, 17/326 miRNAs were changed (7 downregulated; 10 upregulated). There was no overlap in significantly changed miRNAs between isoflurane-exposed males and females. CONCLUSIONS: In the neonatal piglet hippocampus, miRNA expression was highly conserved. There was no overlap in miRNA expression between isoflurane-exposed males and females, suggesting sex differences in isoflurane-induced miRNA expression. These results support the hypothesis that a clinically relevant exposure to isoflurane induces distinct miRNA signatures in the hippocampus of neonatal male and female piglets. Their functional relevance in anesthesia-induced neurotoxicity remains unknown, although changes in specific miRNAs may either contribute to or protect against anesthesia-induced neurotoxicity.

Patient preferences on the use of technology in cancer surveillance after curative surgery: A cross-sectional analysis.

BACKGROUND: Advances in communication technology have enabled new methods of delivering test results to cancer survivors. We sought to determine patient preferences regarding the use of newer technology in delivering test results during cancer surveillance. METHODS: A single institutional, cross-sectional analysis of the preferences of adult cancer survivors regarding the means (secure digital communication versus phone call or office visit) to receive surveillance test results was undertaken. RESULTS: Among 257 respondents, the average age was 59.1 years (SD 13.5) and 61.8% were female. Common malignancies included melanoma/sarcoma (29.5%), thyroid (25.7%), breast (22.8%), and gastrointestinal (22.0%) cancer. Although patients expressed a relative preference to receive normal surveillance results via MyChart or secure e-mail, the majority preferred abnormal imaging (87.2%) or blood results (85.9%) to be communicated by in-office appointments or phone calls irrespective of age or cancer type. Patients with a college degree or higher were more likely to prefer electronic means of communication of abnormal blood results compared with a telephone call or in-person visit (odds ratio 2.18, 95% confidence interval: 1.01-4.73, P < .05). In contrast, patients >65 years were more likely to express a preference for telephone or in-person communication of normal imaging results (odds ratio: 2.03, 95% CI: 1.16-3.56, P < .05) versus patients ≤65 years. Preference also varied according to malignancy type. CONCLUSION: Although many cancer patients preferred to receive "normal" surveillance results electronically, the majority preferred receiving abnormal results via direct conversation with their provider. Shifting routine communication of normal surveillance results to technology-based applications may improve patient satisfaction and decrease health care system costs.

Postoperative Pancreatic Fistula Following Pancreaticoduodenectomy-Stratification of Patient Risk.

BACKGROUND: Postoperative pancreatic fistula (POPF) remains a major cause of morbidity following pancreaticoduodenectomy (PD). We sought to develop and validate a risk score system that utilized preoperative computed tomography (CT) measurements, laboratory values, and intraoperative pancreatic texture to estimate risk of developing POPF after PD. METHODS: Patients who underwent PD between 2014 and 2017 were identified. Pre- and intraoperative risk factors associated with POPF were identified. Three separate risk models were developed and assessed using multivariable analyses and receiver operating curves. RESULTS: Among the 150 patients who underwent a PD, mean age was 64 years and the majority of the patients were male (59.3%, n = 89). Overall, the incidence of BL/POPF following PD was 22%. On multivariable analysis, factors associated with POPF included preoperative total serum protein < 6 g/dL (OR 3.35, 95% CI 1.04-10.34, p = 0.04), radiologic pancreatic duct diameter (OR 0.72, 95% CI 0.53-0.97, p = 0.03), intraoperative pancreatic gland texture estimated by surgeon (OR 0.17, 95% CI 0.05-0.62, p = 0.006), as well as intraoperative pancreatic duct diameter measured by surgeon (OR 0.77, 95% CI 0.61-0.98, p = 0.030). Each risk factor was assigned a weighted score (CT pancreatic duct diameter < 5 mm: 8 points; soft pancreatic gland texture: 5 points; total serum protein < 6 g/dL: 3 points; CT visceral abdominal fat ≥ 230 cm2: 2 points). Patients scoring 4-5 were at low risk of POPF, while patients with a score of 6-18 had a high risk for POPF. The Harrell's c-index for the scoring system was 0.71 (standard error [SD] 0.094) for the training set and 0.67 (SD 0.034) for the test set (with n = 1000 bootstrapping resamples). CONCLUSION: A simple risk score for POPF that utilized preoperative radiologic and clinical variables combined with specific intra-operative factors was able to stratify patients relative to POPF risk with good discriminatory ability.

Spinal anesthesia for pediatric urological surgery: Reducing the theoretic neurotoxic effects of general anesthesia.

BACKGROUND: Spinal anesthesia (SA) is an effective technique that has been used in children for years. With growing concern with regard to the risks of general anesthesia (GA), we developed a SA program to provide an alternative option. We present our initial experience with this program. OBJECTIVE: To implement a SA program at a large tertiary care pediatric center and assess the safety and efficacy of the technique as an alternative to GA for urologic surgery. STUDY DESIGN/METHODS: We prospectively collected data on all children undergoing SA at our institution. We recorded demographics, procedure, time required for placement of the SA, length of surgery, success of lumbar puncture, success of attaining adequate surgical anesthesia, need for supplemental systemic sedation, conversion to GA, and perioperative complications. RESULTS: SA was attempted in 105 consecutive children (104 boys, 1 girl) with a mean age of 7.4 ± 4.3 months (range 19 days-24 months) and mean weight of 8.3 ± 1.7 kg (range 3.5-13.7). Placement of the SA was successful in 93/105 children (89%). Inability to achieve lumbar puncture (cerebrospinal fluid was not obtained) meant that SA was abandoned in seven (7%) patients and GA was administered. In five patients in whom SA was successful and surgery was begun, 5/93 (5%) required conversion to GA: two because of evisceration of intestine through large hernia defects related to coughing and abdominal irritation, two because of lack of motor blockade despite an adequate sensory block, and one because of an inability to place an intravenous catheter in the lower extremities (required per SA protocol). If necessary, an intravenous catheter can be placed in the upper extremity, but this must be weighed against the fact that the block has already been placed and is of limited duration. Overall, SA was successful (SA was placed and surgery was completed without conversion to GA) in 88/105 children (84%). No additional sedation and no systemic anesthetic agents were required in 75/88 children (85%). The average time required to place the SA was 3.8 ± 2.7 min (range 1-12). The average time for the surgical procedure was 38.3 ± 23.1 min (range 10-122). No patient required conversion to GA because of recession of block. There were no surgical complications. DISCUSSION/CONCLUSIONS: SA is a safe and efficacious technique for routine pediatric urological procedures. SA should be considered for cases such as neonatal torsion or patients with significant cardiac or pulmonary comorbidities when the risks of GA are often weighed against the risks of non-intervention.

Selective induction of IL-1ß after a brief isoflurane anesthetic in children undergoing MRI examination.

PURPOSE: To determine if isoflurane anesthesia without surgery causes systemic inflammation in children. Inflammation is targeted as responsible for the development of many neurologic pathologies. The effect will be evaluated by measuring serum cytokine levels before and after isoflurane anesthesia. The possible neurotoxic effect of anesthetic agents is a concern in pediatric anesthesia. Questions remain as to the true effects of anesthesia alone on systemic inflammation. The current study assesses systemic inflammatory response to general anesthesia in children not exposed to surgical stress. METHODS: Twenty-five patients, aged 6 months to 11 years undergoing MRI scanning were recruited. Patients with ASA Physical Status Classification >II, known neurologic disease, prematurity, recent infection, or current treatment with anti-inflammatory medications were excluded. Each patient received a sevoflurane induction, peripheral intravenous catheterization, and laryngeal mask airway placement. Isoflurane was titrated to ensure adequate depth of anesthesia. Two peripheral blood samples were obtained: one immediately after placement of the PIV and one upon arrival to the post-anesthesia care unit. Serum cytokine levels were compared between pre- and post-isoflurane time points using paired t tests. RESULTS: For all patients, interleukin-1ß increased after isoflurane when compared to pre-isoflurane samples (pre = 25.97 ± 9.01, post = 38.53 ± 16.56, p = 0.0002). Serum levels of IL-6 (pre = 2.28 ± 2.27, post = 2.04 ± 2.15, p = 0.146) and tumor necrosis factor-α (pre = 94.26 ± 18.07, post = 85.84 ± 12.12, p = 0.057) were not significantly changed. Interleukin-10 and vascular endothelial growth factor were undetectable in pre- and post-isoflurane samples at a minimum detection threshold of 6.6 and 10 pg/ml, respectively. CONCLUSIONS: A brief (approximately 60 min) exposure to isoflurane general anesthesia, without induced surgical stress, significantly increased serum IL-1ß, a selective activation marker of systemic inflammation (IL-1ß pathway).

Holliday Junction Thermodynamics and Structure: Coarse-Grained Simulations and Experiments.

Holliday junctions play a central role in genetic recombination, DNA repair and other cellular processes. We combine simulations and experiments to evaluate the ability of the 3SPN.2 model, a coarse-grained representation designed to mimic B-DNA, to predict the properties of DNA Holliday junctions. The model reproduces many experimentally determined aspects of junction structure and stability, including the temperature dependence of melting on salt concentration, the bias between open and stacked conformations, the relative populations of conformers at high salt concentration, and the inter-duplex angle (IDA) between arms. We also obtain a close correspondence between the junction structure evaluated by all-atom and coarse-grained simulations. We predict that, for salt concentrations at physiological and higher levels, the populations of the stacked conformers are independent of salt concentration, and directly observe proposed tetrahedral intermediate sub-states implicated in conformational transitions. Our findings demonstrate that the 3SPN.2 model captures junction properties that are inaccessible to all-atom studies, opening the possibility to simulate complex aspects of junction behavior.

Exosome transfer from stromal to breast cancer cells regulates therapy resistance pathways.

Stromal communication with cancer cells can influence treatment response. We show that stromal and breast cancer (BrCa) cells utilize paracrine and juxtacrine signaling to drive chemotherapy and radiation resistance. Upon heterotypic interaction, exosomes are transferred from stromal to BrCa cells. RNA within exosomes, which are largely noncoding transcripts and transposable elements, stimulates the pattern recognition receptor RIG-I to activate STAT1-dependent antiviral signaling. In parallel, stromal cells also activate NOTCH3 on BrCa cells. The paracrine antiviral and juxtacrine NOTCH3 pathways converge as STAT1 facilitates transcriptional responses to NOTCH3 and expands therapy-resistant tumor-initiating cells. Primary human and/or mouse BrCa analysis support the role of antiviral/NOTCH3 pathways in NOTCH signaling and stroma-mediated resistance, which is abrogated by combination therapy with gamma secretase inhibitors. Thus, stromal cells orchestrate an intricate crosstalk with BrCa cells by utilizing exosomes to instigate antiviral signaling. This expands BrCa subpopulations adept at resisting therapy and reinitiating tumor growth.