Changes in holopelagic Sargassum spp. biomass composition across an unusual year.

The year 2021 marked a decade of holopelagic sargassum (morphotypes Sargassum natans I and VIII, and Sargassum fluitans III) stranding on the Caribbean and West African coasts. Beaching of millions of tons of sargassum negatively impacts coastal ecosystems, economies, and human health. Additionally, the La Soufrière volcano erupted in St. Vincent in April 2021, at the start of the sargassum season. We investigated potential monthly variations in morphotype abundance and biomass composition of sargassum harvested in Jamaica and assessed the influence of processing methods (shade-drying vs. frozen samples) and of volcanic ash exposure on biochemical and elemental components. S. fluitans III was the most abundant morphotype across the year. Limited monthly variations were observed for key brown algal components (phlorotannins, fucoxanthin, and alginate). Shade-drying did not significantly alter the contents of proteins but affected levels of phlorotannins, fucoxanthin, mannitol, and alginate. Simulation of sargassum and volcanic ash drift combined with age statistics suggested that sargassum potentially shared the surface layer with ash for ~50 d, approximately 100 d before stranding in Jamaica. Integrated elemental analysis of volcanic ash, ambient seawater, and sargassum biomass showed that algae harvested from August had accumulated P, Al, Fe, Mn, Zn, and Ni, probably from the ash, and contained less As. This ash fingerprint confirmed the geographical origin and drift timescale of sargassum. Since environmental conditions and processing methods influence biomass composition, efforts should continue to improve understanding, forecasting, monitoring, and valorizing sargassum, particularly as strandings of sargassum show no sign of abating.

ARTISTRY-7: phase III trial of nemvaleukin alfa plus pembrolizumab vs chemotherapy for platinum-resistant ovarian cancer.

Standard single-agent nonplatinum chemotherapy provides only modest benefit in a small proportion of patients with platinum-resistant/-refractory ovarian cancer, with objective response rates of 6-20% and progression-free survival of ≈3-4 months. Nemvaleukin alfa (nemvaleukin, ALKS 4230) is a novel cytokine designed to capture and expand the therapeutic potential of high-dose interleukin-2 (IL-2) while mitigating its associated toxicity issues. Nemvaleukin preferentially activates cytotoxic CD8+ T cells and natural killer cells with minimal, non-dose-dependent effects on CD4+ regulatory T cells. The global, randomized, open-label, phase III ARTISTRY-7 trial will compare efficacy and safety of nemvaleukin plus pembrolizumab with chemotherapy in patients with platinum-resistant ovarian cancer. The primary end point is investigator-assessed progression-free survival. Clinical Trial Registration: GOG-3063; ENGOT-OV68; NCT05092360 (ClinicalTrials.gov).

In many patients with ovarian cancer who are treated with platinum-based chemotherapy, the tumor comes back after a few months and fails to respond to repeated treatment. This type of disease is called platinum-resistant ovarian cancer (PROC). Researchers are searching for new medicines to help more patients with PROC. One treatment approach that has shown promise in different cancers is called immunotherapy. These medicines work by helping the body's immune system attack cancer cells. One of the immunotherapies being studied is called nemvaleukin. It is designed to trigger specific immune responses that may result in the immune system attacking cancer cells while potentially avoiding other immune responses that can block the attack or cause certain unwanted side effects. Nemvaleukin is being studied in a variety of cancer types. In a worldwide clinical trial called ARTISTRY-7, researchers are investigating how nemvaleukin works in patients with PROC when given with another immunotherapy called pembrolizumab. Patients who participate in this trial will be randomly assigned to one of four treatment groups: the combination of nemvaleukin and pembrolizumab, nemvaleukin by itself, pembrolizumab by itself, or a type of chemotherapy selected by the treating physician. The main purpose of ARTISTRY-7 is to understand whether the combination of nemvaleukin and pembrolizumab helps patients with PROC live longer without their cancer getting worse. At the time of this writing, ARTISTRY-7 is open for new patients to join.

Feasibility and Morbidity for the Use of MR-Guided Laser-Induced Thermotherapy for the Treatment of Skull Base Tumors: A Report of Three Cases.

Background Laser-induced thermotherapy (LITT) is a minimally invasive technique that has been demonstrated as an effective treatment of many pathologies; however, it has never been investigated for the use in skull base tumors. Case Series Three patients underwent LITT for treatment of skull base meningiomas. All three patients were determined to be poor candidates for open resection. Each patient was treated with a single laser fiber. Postoperative imaging confirmed ablation zones along the tract of the catheter in all three patients. Ablation zones were estimated to be 9 to 20% of the intended to treat tumor volume. Two of three treated patients suffered cranial nerve injury following the procedure with one patient diagnosed with neurotrophic keratitis and one patient with symptoms consistent with anesthesia dolorosa. Conclusion LITT is a technically feasible, minimally invasive treatment modality for skull base lesions. Significant risk to cranial nerves and small ablation zones afforded by a single cannula placement proposes serious obstacles. Further investigation is warranted prior to using this technique outside of a palliative indication.

Contralateral Transmaxillary Approach for Resection of Chondrosarcoma of the Petrous Apex: A Case Report.

BACKGROUND: Deep location and neurovascular structures make access to lesions of the petrous apex a significant challenge. A novel approach for these tumors is the contralateral transmaxillary approach. CLINICAL PRESENTATION: A 31-year-old male was evaluated for left abducens nerve palsy. Magnetic resonance imaging (MRI) and computed tomography revealed an enhancing, lytic lesion of the petrous apex with extension to the cavernous sinus and petroclival junction. The patient underwent a combined endoscopic contralateral transmaxillary and endoscopic endonasal transclival approach for resection of the lesion. No new or worsening neurologic deficits were noted following the procedure. Pathology revealed low-grade chondrosarcoma (grade I). Postoperative MRI revealed gross total resection of the lesion. Patient underwent adjuvant radiation therapy at the discretion of radiation oncology. CONCLUSION: The contralateral transmaxillary approach to the petrous apex allows for resection of lesions of the petrous apex with the ability to extend the dissection laterally. Excellent results achieved by institutions with advanced extended endoscopic endonasal experience can be reproduced in institutions with less experience. Further characterization of the risks and benefits of this approach is needed.

Efficacy of Preoperative mFOLFIRINOX vs mFOLFIRINOX Plus Hypofractionated Radiotherapy for Borderline Resectable Adenocarcinoma of the Pancreas: The A021501 Phase 2 Randomized Clinical Trial.

Importance: National guidelines endorse treatment with neoadjuvant therapy for borderline resectable pancreatic ductal adenocarcinoma (PDAC), but the optimal strategy remains unclear. Objective: To compare treatment with neoadjuvant modified FOLFIRINOX (mFOLFIRINOX) with or without hypofractionated radiation therapy with historical data and establish standards for therapy in borderline resectable PDAC. Design, Setting, and Participants: This prospective, multicenter, randomized phase 2 clinical trial conducted from February 2017 to January 2019 among member institutions of National Clinical Trials Network cooperative groups used standardized quality control measures and included 126 patients, of whom 70 (55.6%) were registered to arm 1 (systemic therapy; 54 randomized, 16 following closure of arm 2 at interim analysis) and 56 (44.4%) to arm 2 (systemic therapy and sequential hypofractionated radiotherapy; all randomized before closure). Data were analyzed by the Alliance Statistics and Data Management Center during September 2021. Interventions: Arm 1: 8 treatment cycles of mFOLFIRINOX (oxaliplatin, 85 mg/m2; irinotecan, 180 mg/m2; leucovorin, 400 mg/m2; and infusional fluorouracil, 2400 mg/m2) over 46 hours, administered every 2 weeks. Arm 2: 7 treatment cycles of mFOLFIRINOX followed by stereotactic body radiotherapy (33-40 Gy in 5 fractions) or hypofractionated image-guided radiotherapy (25 Gy in 5 fractions). Patients without disease progression underwent pancreatectomy, which was followed by 4 cycles of treatment with postoperative FOLFOX6 (oxaliplatin, 85 mg/m2; leucovorin, 400 mg/m2; bolus fluorouracil, 400 mg/m2; and infusional fluorouracil, 2400 mg/m2 over 46 hours). Main Outcomes and Measures: Each treatment arm's 18-month overall survival (OS) rate was compared with a historical control rate of 50%. A planned interim analysis mandated closure of either arm for which 11 or fewer of the first 30 accrued patients underwent margin-negative (R0) resection. Results: Of 126 patients, 62 (49%) were women, and the median (range) age was 64 (37-83) years. Among the first 30 evaluable patients enrolled to each arm, 17 patients in arm 1 (57%) and 10 patients in arm 2 (33%) had undergone R0 resection, leading to closure of arm 2 but continuation to full enrollment in arm 1. The 18-month OS rate of evaluable patients was 66.7% (95% CI, 56.1%-79.4%) in arm 1 and 47.3% (95% CI 35.8%-62.5%) in arm 2. The median OS of evaluable patients in arm 1 and arm 2 was 29.8 (95% CI, 21.1-36.6) months and 17.1 (95% CI, 12.8-24.4) months, respectively. Conclusions and Relevance: This randomized clinical trial found that treatment with neoadjuvant mFOLFIRINOX alone was associated with favorable OS in patients with borderline resectable PDAC compared with mFOLFIRINOX treatment plus hypofractionated radiotherapy; thus, mFOLFIRINOX represents a reference regimen in this setting. Trial Registration: ClinicalTrials.gov Identifier: NCT02839343.

Assessing the effectiveness of microplastic extraction methods on fishmeal with different properties.

Microplastic presence in fishmeal is an emerging research area because of its potential to enter food chains, and the importance of fishmeal within global food security. However, fishmeal is a complex medium dependant on fish composition. This study measured properties (organics, carbonates, protein and density) of five fishmeal types (trimmings, sardine and anchovy, krill, tuna and salmon), sourced from locations worldwide (Norway, South America, Antarctica, Spain and Scotland). Microplastic recovery rates were compared for existing methodologies using sodium chloride overflows and potassium hydroxide digestions and then compared to newly developed methods. These methods included dispersants and calcium chloride density separations which were developed and designed to be environmentally conscious and affordable, which we argue should become an international standard approach for researchers. A calcium chloride overflow with dispersant and potassium hydroxide digestion provided the highest recovery rate in sardine and anchovy fishmeal (66.3%). Positive correlations with recovery rate were found with protein content, and negative correlations with organic content. Low recovery rates found here suggest microplastics in fishmeal reported in the literature are underestimated. With complex media such as fishmeal, attention must be paid to variation between types and composition when choosing methods and interpreting results.

Infratemporal Fossa Vascular Anatomy Pertinent to Percutaneous Access to the Foramen Ovale for Treatment of Trigeminal Neuralgia: A Comparison of Cadaveric Dissection and Computed Tomography Analysis.

BACKGROUND: Trigeminal neuralgia may be treated via percutaneous access to the foramen ovale (FO). Vascular complications associated with the needle trajectory can result in serious morbidity and mortality. This study aimed to correlate the vascular relationships of the FO at the skull base via cadaveric dissections and computed tomography (CT). METHODS: Two fresh cadaver heads were injected with red and blue latex to delineate arteries and veins. Neck and infratemporal fossa dissections were carried out to delineate the vascular relationships of the FO. High-resolution head CT images of adult patients undergoing neurosurgical evaluations or procedures were analyzed for distances and sizes of skull base foramina in the infratemporal fossa. RESULTS: Three infratemporal fossa dissections (2 cadaveric specimens) were performed. Mean distance of FO to internal carotid artery was 2.4 ± 0.12 cm, and mean distance of FO to middle meningeal artery was 0.8 ± 0.16 cm. Head CT images of 52 patients (104 sides) with 1-mm axial slice thickness were analyzed. Area of the FO was 31.1 ± 9.6 mm2. Distance of FO to internal carotid artery was 1.70 ± 0.31 cm, and distance of FO to middle meningeal artery was 0.73 ± 0.61 cm. CONCLUSIONS: Cadaveric delineation of vascular structures in the infratemporal fossa correlates with head CT imaging and may be used to accurately plan percutaneous access to the FO. Inadvertent puncture of the extracranial internal carotid artery is nearly impossible with good technique. The most likely source of percutaneous vascular injury is the middle meningeal artery and distal branches of the maxillary artery.

Pelagic Sargassum events in Jamaica: Provenance, morphotype abundance, and influence of sample processing on biochemical composition of the biomass.

Pelagic Sargassum species have been known for centuries in the Sargasso Sea of the North Atlantic Ocean. In 2011, a new area concentrating high biomass of these brown algae started developing in the Tropical Atlantic Ocean. Since then, massive and recurrent Sargassum influxes have been reported in the Caribbean and off the coast of Western Africa. These Sargassum events have a major negative impact on coastal ecosystems and nearshore marine life, and affect socio-economic sectors, including public health, coastal living, tourism, fisheries, and maritime transport. Despite recent advances in the forecasting of Sargassum events, and elucidation of the seaweed composition, many knowledge gaps remain, including morphotype abundance during Sargassum events, drift of the seaweeds in the months prior to stranding, and influence of sample processing methods on biomass biochemical composition. Using seaweeds harvested on the coasts of Jamaica in summer of 2020, we observed that S. fluitans III was the most abundant morphotype at different times and sampling locations. No clear difference in the geographical origin, or provenance, of the Sargassum mats was observed. The majority of Sargassum backtracked from both north and south of Jamaica experienced ambient temperatures of around 27 °C and salinity in the range of 34-36 psu before stranding. We also showed that cheap (sun) compared to expensive (freeze) drying techniques influence the biochemical composition of biomass. Sun-drying increased the proportion of phenolic compounds, but had a deleterious impact on fucoxanthin content and on the quantities of monosaccharides, except for mannitol. Effects on the content of fucose containing sulfated polysaccharides depended on the method used for their extraction, and limited variation was observed in ash, protein, and fatty acid content within most of the sample locations investigated. These observations are important for the storage and transport of the biomass in the context of its valorisation.

Endovascular management of portal vein obstruction in hepatobiliary cancer patients.

BACKGROUND AND OBJECTIVES: The purpose of this article is to describe the procedural safety, technical success, and clinical success of endovascular management of portal and mesenteric venous obstruction in patients with hepatobiliary neoplasms. METHODS: Institutional Review Board (IRB)-approved HIPAA compliant retrospective review of 21 consecutive patients with hepatobiliary malignancies who underwent endovascular portal vein recanalization and stent placement between January 2012 and March 2020. Clinical diagnoses were pancreatic cancer (n = 19), colon cancer metastatic to the liver (n = 1), and cholangiocarcinoma (n = 1). Presenting signs and symptoms included: ascites, abdominal pain, abnormal liver function tests, diarrhea, and gastrointestinal bleeding. Stent patency and patient survival are presented with Kaplan-Meier method. RESULTS: The technical success rate was 100%. A transhepatic approach was used in 20 cases (95.2%); trans-splenic access in one. Primary stent patency was 95.2%, 84%, and 68% at 1, 3, and 6 months, respectively. All stent occlusions were caused by tumor progression. A total of 80% of patients reported symptomatic improvement. Patient survival at 10 months was 40%. The early death rate was 4.76%. There were no bleeding complications from the percutaneous tracts. CONCLUSION: Endovascular recanalization with stent placement is safe with high technical and clinical success.

Management of colorectal cancer during the COVID-19 pandemic: Recommendations from a statewide multidisciplinary cancer collaborative.

COVID-19 has resulted in significant disruptions in cancer care. The Illinois Cancer Collaborative (ILCC), a statewide multidisciplinary cancer collaborative, has developed expert recommendations for triage and management of colorectal cancer when disruptions occur in usual care. Such recommendations would be applicable to future outbreaks of COVID-19 or other large-scale disruptions in cancer care.

Robotic-Navigated Percutaneous Pedicle Screw Placement Has Less Facet Joint Violation Than Fluoroscopy-Guided Percutaneous Screws.

OBJECTIVE: To directly compare robotic-versus fluoroscopy-guided percutaneous pedicle screw (PPS) placement in thoracolumbar spine trauma with a focus on clinically acceptable pedicle screw accuracy and facet joint violation (FJV). METHODS: A retrospective chart review assessed 37 trauma patients undergoing percutaneous thoracic and/or lumbar fixation. Postoperative computed tomography images were reviewed by authors blinded to surgical technique who assessed pedicle screw trajectory accuracy and FJV frequency. RESULTS: Seventeen patients underwent placement of 143 PPS with robotic assistance (robot group), compared with 20 patients receiving 149 PPS using fluoroscopy assistance (control group). Overall, the robot cohort demonstrated decreased FJV frequency of 2.8% versus 14.8% in controls (P = 0.0003). When further stratified by level of surgery (i.e., upper thoracic, lower thoracic, lumbar spine), the robot group had FJV frequencies of 0%, 3.2%, and 3.7%, respectively, compared with 17.7% (P = 0.0209), 14.3% (P = 0.0455), and 11.9% (P = 0.2340) in controls. The robot group had 84.6% clinically acceptable screw trajectories compared with 81.9% in controls (P = 0.6388). Within the upper thoracic, lower thoracic, and lumbar regions, the robot group had acceptable screw trajectories of 66.7%, 87.1%, and 90.7%, respectively, compared with 58.8% (P = 0.6261), 91.1% (P = 0.5655), and 97.6% (P = 0.2263) in controls. CONCLUSIONS: There was no significant difference in clinically acceptable screw trajectory accuracy between robotic versus fluoroscopy-guided PPS placement. However, the robot cohort demonstrated a statistically significantly decreased FJV overall and specifically within the thoracic spine region. Use of robotic technology may improve radiographic outcomes for a subset of patients or spine surgeries.

Burr-Hole Evacuation of an Acute Epidural Hematoma using the Artemis Neuroevacuation Device With Flexible Endoscopic Visualization: 2-Dimensional Operative Video.

Minimally invasive (MIS) endoscopic burr-hole evacuation of both acute and subacute subdural hematomas (SDHs) has been demonstrated as a way to avoid large craniotomies and additional morbidity, particularly for patients who are poor surgical candidates.1,2 Although generally safe and effective, there are risks of complications including SDH recurrence or new hemorrhage including epidural hematoma (EDH).3,4 Acute intraparenchymal hemorrhage has also been successfully treated using MIS endoscopic techniques with the assistance of aspiration devices; however, acute EDHs generally still necessitate a craniotomy for evacuation, nullifying many of the advantages of burr-hole craniostomy.5,6 In this surgical video, we demonstrate-to our knowledge-the first case of endoscopic burr-hole evacuation of an acute EDH using an Artemis Neuro Evacuation device (Penumbra, Alameda, CA). We present the case of a 40 year-old man with a left anterior middle cranial fossa arachnoid cyst who developed a traumatic left subacute SDH and hemorrhage into the cyst. He underwent burr-hole craniostomy for endoscopic evacuation of subacute SDH, evacuation of hemorrhage within the cyst, and fenestration of arachnoid cyst. On postoperative day 2, he developed an acute left EDH with midline shift. An Artemis device was inserted into 1 of the pre-existing burr-holes and used to evacuate the acute EDH with direct visualization from a flexible endoscope inserted into the second burr-hole. The patient did well, was discharged 2 days later, and demonstrated complete resolution of hemorrhage 5 weeks post-procedure. The video also provides a brief background on arachnoid cysts, their association with hemorrhage, and MIS techniques for hemorrhage evacuation.7-12 There is no identifying information in the video. The patient provided informed consent for both procedures (Video 1).

Retrospective Assessment of the Use of Liposomal Bupivacaine in Lumbar Fusions in Immediate Postoperative Hospital Care.

BACKGROUND: Liposomal bupivacaine (LB) is approved by the U.S. Food and Drug Administration for administration into surgical sites for postsurgical analgesia. The liposomal formulation allows for sustained effects up to 72 hours. METHODS: A retrospective study assessed patients undergoing lumbar interbody surgery. Visual analog scale pain scores and amount of opioids consumed were recorded at 12-hour intervals for 72 hours postoperatively, as were patterns of discharge and hospital length of stay (LOS). RESULTS: A total of 122 patients (97 LB vs. 25 control group) were reviewed. Median LOS was shorter in the LB cohort compared with controls (1.94 vs. 3.08 days, respectively; P = 0.0043). When assessing the percentage of discharges between groups at 12-hour intervals, there were significantly more discharges in the LB cohort at 36-48 hours (P = 0.0226), and no differences elsewhere. There was a decrease in intravenous opioids consumed at 48-60 hours in the LB cohort compared with controls (P = 0.0494), a difference not detected at other time points or with oral or total opioids. Mean visual analog scale scores were significantly higher in the LB cohort compared with controls at 0-12 hours (5.2 vs. 3.9, respectively; P = 0.0079), but insignificantly different subsequently up to 72 hours. The LB cohort and controls were not significantly different in total amount of opioids consumed, overall pain scores, or regarding how the opioid amount consumed or pain scores changed over time. CONCLUSIONS: The use of LB in lumbar interbody fusion decreases patients' LOS but has little effect on reducing overall pain scores or opioid use in the 72-hour postoperative hospital period.

Evaluation of the Association of Perioperative UGT1A1 Genotype-Dosed gFOLFIRINOX With Margin-Negative Resection Rates and Pathologic Response Grades Among Patients With Locally Advanced Gastroesophageal Adenocarcinoma: A Phase 2 Clinical Trial.

Importance: Patients with locally advanced gastroesophageal adenocarcinoma (ie, stage ≥T3 and/or node positive) have high rates of recurrence despite surgery and adjunctive perioperative therapies, which also have high toxicity profiles. Evaluation of pharmacogenomically dosed perioperative gFOLFIRINOX (fluorouracil, leucovorin, oxaliplatin, and UGT1A1 genotype-directed irinotecan) to optimize efficacy while limiting toxic effects may have value. Objective: To evaluate the coprimary end points of margin-negative (R0) resection rates and pathologic response grades (PRGs) of gFOLFIRINOX therapy among patients with locally advanced gastroesophageal adenocarcinoma. Design, Setting, and Participants: This single-group phase 2 trial, conducted at 2 academic medical centers from February 2014 to March 2019, enrolled 36 evaluable patients with locally advanced adenocarcinoma of the esophagus, gastroesophageal junction, and gastric body. Data analysis was conducted in May 2019. Interventions: Patients received biweekly gFOLFIRINOX (fluorouracil, 2400 mg/m2 over 46 hours; oxaliplatin, 85 mg/m2; irinotecan, 180 mg/m2 for UGT1A1 genotype 6/6, 135 mg/m2 for UGT1A1 genotype 6/7, or 90 mg/m2 for UGT1A1 genotype 7/7; and prophylactic peg-filgastrim, 6 mg) for 4 cycles before and after surgery. Patients with tumors positive for ERBB2 also received trastuzumab (6-mg/kg loading dose, then 4 mg/kg). Main Outcomes and Measures: Margin-negative resection rate and PRG. Results: A total of 36 evaluable patients (27 [78%] men; median [range] age, 66 [27-85] years; 10 [28%] with gastric body cancer; 24 [67%] with intestinal-type tumors; 6 [17%] with ERBB2-positive tumors; 19 [53%] with UGT1A1 genotype 6/6; 16 [44%] with genotype 6/7; and 1 [3%] with genotype 7/7) were enrolled. Of these, 35 (97%) underwent surgery; 1 patient (3%) died after completing neoadjuvant chemotherapy while awaiting surgery. Overall, R0 resection was achieved in 33 of 36 patients (92%); 2 patients (6%) with linitis plastica achieved R1 resection. Pathologic response grades 1, 2, and 3 occurred in 13 patients (36%), 9 patients (25%), and 14 patients (39%), respectively, and PRG 1 was observed in 11 of 24 intestinal-type tumors (46%). Median disease-free survival was 30.1 months (95% CI, 15.0 months to not reached), and median overall survival was not reached (95% CI, 8.3 months to not reached). There were no differences in outcomes by UGT1A1 genotype group. A total of 38 patients, including 2 (5%) with antral tumors, were evaluable for toxic effects. Grade 3 or higher adverse events occurring in 5% or more of patients during the perioperative cycles included diarrhea (7 patients [18%]; 3 of 19 patients [16%] with genotype 6/6; 2 of 16 patients [13%] with genotype 6/7; 2 of 3 patients [67%] with genotype 7/7), anemia (2 patients [5%]), vomiting (2 patients [5%]), and nausea (2 patients [5%]). Conclusions and Relevance: In this study, perioperative pharmacogenomically dosed gFOLFIRINOX was feasible, providing downstaging with PRG 1 in more than one-third of patients and an R0 resection rate in 92% of patients. Trial Registration: ClinicalTrials.gov Identifier: NCT02366819.

Clinical Assessment of 5-Fluorouracil/Leucovorin, Nab-Paclitaxel, and Irinotecan (FOLFIRABRAX) in Untreated Patients with Gastrointestinal Cancer Using UGT1A1 Genotype-Guided Dosing.

PURPOSE: 5-Fluorouracil (5-FU)/leucovorin, irinotecan, and nab-paclitaxel are all active agents in gastrointestinal cancers; the combination, FOLFIRABRAX, has not been previously evaluated. UDP Glucuronosyltransferase 1A1 (UGT1A1) clears SN-38, the active metabolite of irinotecan. UGT1A1*28 polymorphism reduces UGT1A1 enzymatic activity and predisposes to toxicity. We performed a trial to assess the safety and tolerability of FOLFIRABRAX with UGT1A1 genotype-guided dosing of irinotecan. PATIENTS AND METHODS: Patients with previously untreated, advanced gastrointestinal cancers received FOLFIRABRAX with prophylactic pegfilgrastim every 14 days. UGT1A1 *1/*1, *1/*28, and *28/*28 patients received initial irinotecan doses of 180, 135, and 90 mg/m2, respectively. 5-FU 2,400 mg/m2 over 46 hours, leucovorin 400 mg/m2, and nab-paclitaxel 125 mg/m2 were administered. Doses were deemed tolerable if the dose-limiting toxicity (DLT) rate during cycle 1 was ≤35% in each genotype group. DLTs were monitored using a sequential procedure. RESULTS: Fifty patients enrolled, 30 pancreatic, 9 biliary tract, 6 gastroesophageal, and 5 others. DLTs occurred in 5 of 23 (22%) *1/*1 patients, 1 of 19 (5%) *1/*28 patients, and 0 of 7 *28/*28 patients. DLTs were all grade 3: diarrhea (3 patients), nausea (2 patients), and febrile neutropenia (1 patient). The overall response rate was 31%. Response rates in pancreatic, gastroesophageal, and biliary tract cancers were 34%, 50%, and 11%, respectively. Eighteen patients (36%) received therapy for at least 24 weeks. CONCLUSIONS: FOLFIRABRAX with genotype-guided dosing of irinotecan is tolerable in patients with advanced gastrointestinal cancer and UGT1A1*1*1 or UGT1A1*1*28 genotypes. Too few *28/*28 patients were enrolled to provide conclusive results. Responses occurred across multiple tumor types.

Pathologic Response to Primary Systemic Therapy With FOLFIRINOX in Patients With Resectable Pancreatic Cancer.

BACKGROUND: Primary systemic therapy in resectable pancreatic cancer is currently under investigation. FOLFIRINOX has been shown to be effective in both the adjuvant and metastatic settings and is increasingly being used on and off study in the neoadjuvant setting. The objective pathologic response elicited by this regimen in truly resectable disease has not as yet been widely reported. METHODS: This analysis focuses on 14 patients with resectable pancreatic cancer who were treated in a pilot study of primary systemic therapy, using 4 cycles of neoadjuvant FOLFIRINOX before surgery. A dedicated pancreatic pathologist reviewed all of the subsequent surgical specimens to assess the degree of tumor regression elicited by this approach, according to the scoring system proposed by Evans. RESULTS: Four patients (28.6%) had Evans grade I, 4 (28.6%) Evans grade IIa, 2 (14.2%) Evans grade IIb, and 4 (28.6%) Evans grade III response to the primary systemic therapy. There were no Evans grade IV responses. CONCLUSIONS: The results are intriguing with 28% of the specimens showing destruction of <10% of tumor cells, and only 28% achieving >90% destruction of tumor cells. The significant variation in response once again confirms the known heterogeneity in the biology of this cancer and clearly FOLFIRINOX is not equally effective in all patients. Future studies evaluating primary systemic therapy in pancreatic cancer should examine the optimal duration of therapy before surgery and should include a standardized pathologic grading scheme to better enable comparison of results.

Ocean precursors to the extreme Atlantic 2017 hurricane season.

Active Atlantic hurricane seasons are favoured by positive precursor sea surface temperature anomalies (SSTA) in the main development region (MDR, 10-20°N, 20-80°W). Here, we identify a different driving mechanism for these anomalies in 2017 (most costly season on record) compared to the recent active 2005 and 2010 seasons. In 2005 and 2010, a weakened Atlantic Meridional Overturning Circulation is the primary driver of positive SSTA. However, in 2017, reduced wind-driven cold water upwelling and weaker surface net heat loss in the north-eastern MDR were the main drivers. Our results are the first to show that air-sea heat flux and wind stress related processes are important in generating precursor positive SSTAs and that these processes were active pre-determinants of the 2017 season severity. In contrast to other strong seasons, positive SSTA developed later in 2017 (between April and July rather than March) compounding the challenge of predicting Atlantic hurricane season severity.

Management of Opioid Use Disorder Treatment: An Overview.

It is important for nurses not working in the area of addictions to be informed of the diagnosis and treatment of opioid use disorder so that they may serve as a resource, educate others, and influence and refer individuals to seek treatment on the basis of best evidence. In this article, we provide an overview of the postscreening diagnosis and treatment of opioid use disorders with an emphasis on medication-assisted treatment, starting with the definition of substance use disorder, tolerance, dependence, and addiction.

A UGT1A1 genotype-guided dosing study of modified FOLFIRINOX in previously untreated patients with advanced gastrointestinal malignancies.

BACKGROUND: FOLFIRINOX (5-fluorouracil [5-FU], leucovorin, irinotecan, oxaliplatin) is an effective but toxic therapy for pancreatic cancer. UGT1A1 (UDP glucuronosyltransferase 1A1) eliminates the active metabolite of irinotecan. Polymorphisms reduce UGT1A1 activity, leading to toxicity. The primary objective was to determine the dose-limiting toxicity (DLT) rate in cycle 1 of modified FOLFIRINOX (mFOLFIRINOX) using genotype-guided dosing of irinotecan for the most common UGT1A1 genotypes (*1/*1, *1/*28) in advanced gastrointestinal malignancies, with expansion in pancreatic and biliary tract cancers. METHOD: 5-FU (2400 mg/m2 over 46 hours), leucovorin (400 mg/m2 ), oxaliplatin (85 mg/m2 ), and irinotecan were given every 14 days. Irinotecan doses of 180, 135, and 90 mg/m2 were administered for UGT1A1 genotypes *1/*1, *1/*28, and *28/*28, respectively. Prophylactic pegfilgrastim was omitted in cycle 1 for cohort 1 (tolerability by genotype), but was given in cohort 2 (tolerability by tumor type). Doses were tolerable if the upper limit of a 2-sided 80% confidence interval for DLT rate was ≤33%. RESULTS: In cohort 1, DLTs (most commonly febrile neutropenia, fatigue, diarrhea) occurred in 2/15 (13%), 3/16 (19%), and 4/10 (40%) patients with *1/*1, *1/*28, and *28/*28 genotypes, respectively. In cohort 2, 6/19 (32%) pancreatic and 4/19 (21%) biliary tract cancer patients experienced DLTs (most commonly fatigue, diarrhea, nausea/vomiting). In cohort 2, upper confidence limits of DLT rates exceeded 33%. Response rates were 38% in pancreatic and 21% in biliary tract cancers. CONCLUSION: On the basis of our prespecified criteria, tolerability of UGT1A1 genotype-guided mFOLFIRINOX was not established in pancreatic and biliary tract cancers. However, this regimen was effective.

Using the "Patient Generated Index" in Spine Surgery in an Appalachian Population.

In most health care fields, outcomes are becoming increasingly scrutinized and may play a role in "pay for performance;" therefore, selecting the most appropriate outcomes measures for the populations being studied or treated has evolved into a key aspect of outcomes monitoring. One way to assess patient goals is to administer a "patient generated index" (PGI). The philosophical underpinning of the PGI is that the person living the life is the best judge of the quality of that life. The PGI has been utilized in low back pain, as well as in adult spinal deformity surgery, however, it has not been previously utilized in an Appalachian population. The PGI was administered by means of self-report to 80 new patients with back pain who presented for assessment in the neurosurgery clinic. Participants completed an acceptability survey and written comments as well as compliance were analyzed. Findings indicate that the PGI in its earliest form did not meet acceptable levels for use in this Appalachian subspecialist clinic setting. This study contributes to the growing body of knowledge on patient reported outcomes and more specifically, the importance of utilizing patient generated responses to map improvements in quality of life for patients over time.