St Mary's Hospital

OBJECTIVE: To provide evidence-based recommendations and expert guidance for the management of antineutrophil cytoplasmic antibody-associated vasculitis (AAV), including granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). METHODS: Clinical questions regarding the treatment and management of AAV were developed in the population, intervention, comparator, and outcome (PICO) format (47 for GPA/MPA, 34 for EGPA). Systematic literature reviews were conducted for each PICO question. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to assess the quality of evidence and formulate recommendations. Each recommendation required ≥70% consensus among the Voting Panel. RESULTS: We present 26 recommendations and 5 ungraded position statements for GPA/MPA, and 15 recommendations and 5 ungraded position statements for EGPA. This guideline provides recommendations for remission induction and maintenance therapy as well as adjunctive treatment strategies in GPA, MPA, and EGPA. These recommendations include the use of rituximab for remission induction and maintenance in severe GPA and MPA and the use of mepolizumab in nonsevere EGPA. All recommendations are conditional due in part to the lack of multiple randomized controlled trials and/or low-quality evidence supporting the recommendations. CONCLUSION: This guideline presents the first recommendations endorsed by the American College of Rheumatology and the Vasculitis Foundation for the management of AAV and provides guidance to health care professionals on how to treat these diseases.

OBJECTIVE: To provide evidence-based recommendations and expert guidance for the management of giant cell arteritis (GCA) and Takayasu arteritis (TAK) as exemplars of large vessel vasculitis. METHODS: Clinical questions regarding diagnostic testing, treatment, and management were developed in the population, intervention, comparator, and outcome (PICO) format for GCA and TAK (27 for GCA, 27 for TAK). Systematic literature reviews were conducted for each PICO question. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to rate the quality of the evidence. Recommendations were developed by the Voting Panel, comprising adult and pediatric rheumatologists and patients. Each recommendation required ≥70% consensus among the Voting Panel. RESULTS: We present 22 recommendations and 2 ungraded position statements for GCA, and 20 recommendations and 1 ungraded position statement for TAK. These recommendations and statements address clinical questions relating to the use of diagnostic testing, including imaging, treatments, and surgical interventions in GCA and TAK. Recommendations for GCA include support for the use of glucocorticoid-sparing immunosuppressive agents and the use of imaging to identify large vessel involvement. Recommendations for TAK include the use of nonglucocorticoid immunosuppressive agents with glucocorticoids as initial therapy. There were only 2 strong recommendations; the remaining recommendations were conditional due to the low quality of evidence available for most PICO questions. CONCLUSION: These recommendations provide guidance regarding the evaluation and management of patients with GCA and TAK, including diagnostic strategies, use of pharmacologic agents, and surgical interventions.

The purpose of tumour staging for colorectal cancer (CRC) is to help define clinical management, facilitate communication between physicians, provide a basis for stratification and analysis of treatment results in prospective studies, and provide some prognostic information for patients and their families. The World Congresses of Gastroenterology, Digestive Endoscopy, and Coloproctology, Working Party on staging for CRC studied six commonly used systems to review their strengths and weaknesses. Although it was concluded that defining a new staging system was unnecessary, it was recognized that there is a need to define a terminology to describe the full anatomic extent of spread of CRC. Furthermore, we note that there are several additional features, derived from both clinical and pathology information, which have had prognostic significance shown by appropriately constructed multivariate analyses and which can be used to formulate a more accurate prognostic index than that provided by a description of anatomical tumour spread. Thus the Working Party came to two principal conclusions. First, a standard format should be adopted for the collection of the essential data required for prospective studies, and we recommend the 'International Documentation System (IDS) for CRC' for this purpose. Second, a nomenclature which describes the full anatomical extent of tumour spread and residual tumour status in CRC has been defined and should be adopted, from which all currently used staging systems can be derived. We have called this nomenclature the 'International Comprehensive Anatomical Terminology (ICAT) for CRC'. In the event that these recommendations are adopted, we envision that there will be improved clarity in the documentation of treatment outcome for patients with CRC and improved communication of results derived from prospective studies. Furthermore, an acceptance of IDS and ICAT would set the scene to develop a prognostic index for individual patients with CRC by the expansion of anatomical clinicopathology staging information to include additional factors which have independent prognostic significance.

Cytologic examinations of sputum collected periodically since 1957 on a group of uranium miners have been studied and related to the development of bronchogenic carcinoma. Many individuals developed abnormal squamous cell metaplasia that gradually progressed, in several, to develop invasive carcinoma. This progression has been classified into mild, moderate, and marked atypical, squamous cell metaplasias and carcinoma in situ. Cigarette smoking and uranium mining were both associated with the prevalence of these atypias, and with carcinoma in situ and invasive cancer. Neither of these agents, however, appeared to be strongly associated with the duration of the stages of atypia. Age at start of uranium mining was more strongly associated with age at development of carcinoma in situ than other factors tested. There appears to be an average period of 4 or 5 years during which individuals exfoliate cells that are markedly atypical or represent carcinoma in situ in their sputum before developing invasive carcinoma of epidermoid or small cell, undifferentiated varieties. Periodic sputum surveillance of groups at elevated risk of bronchogenic cancer can utilize this period for early detection and treatment.

Shear stress is the tangential force of the flowing blood on the endothelial surface of the blood vessel. Shear is described mathematically or ideal fluids, and in vitro models have enabled researchers to describe the effects of shear on endothelial cells. High shear stress, as found in laminar flow, promotes endothelial cell survival and quiescence, alignment in the direction of flow, and secretion of substances that promote vasodilation and anticoagulation. Low shear stress, or changing shear stress direction as found in turbulent flow, promotes endothelial proliferation and apoptosis, shape change, and secretion of substances that promote vasoconstriction, coagulation, and platelet aggregation. The precise pathways by which endothelial cells sense shear stress to promote their quiescent or activated pathways are currently unknown. Clinical applications include increasing shear stress via creation of an arteriovenous fistula or vein cuff to promote bypass graft flow and patency. Since an abnormal level of shear stress is implicated in the pathogenesis of atherosclerosis, neointimal hyperplasia, and aneurysmal disease, additional research to understand the effects of shear stress on the blood vessel may provide insight to prevent vascular disease.

The incidence of colorectal cancer in the United States is increasing. Because more than half of patients with colorectal cancer have liver metastases develop, the number of patients with hepatic metastases also is increasing. Unfortunately, metastatic disease will be limited to the liver in perhaps 25% of these patients and confined to only one lobe of the liver 25% of this subgroup. Consequently, solitary or unilobar colorectal metastases are found in as few as 5% of patients with colorectal cancer. The median survival of patients with unresected hepatic metastases is approximately 10.6 months. Patients with solitary lesions or small tumor burdens may attain a median survival of 16-20 months, but 5-year survivors are extremely rare. In contrast, rates of 5-year survival average approximately 36% after resections of solitary hepatic lesions and may approach the same level in selected patients with multiple lesions. Factors that appear to adversely effect survival include detection of metastatic disease because of signs or symptoms of disease, an elevated carcinoembryonic antigen (CEA) level, elevated liver function tests, poorly differentiated primary lesions, lymph node-positive primary lesions, extrahepatic sites of metastases, more than four hepatic lesions, bilobar disease, a satellite pattern of metastases in the liver, positive margins of the liver resection, positive extrahepatic lymph nodes, and more than 10 units of blood transfusion during the perioperative period. Operative mortality for liver resections should remain approximately 4%, and major morbidity should be in the range of 20-30%. Modalities other than surgical resection have not improved survival in patients with colorectal hepatic metastases. Thus, when feasible, patients with metastatic colorectal cancer limited to one lobe of the liver should undergo hepatic resection. Unfortunately, only approximately 5% of patients with colorectal cancer fall into this category, so resection of hepatic metastases can improve overall survival of patients with colorectal cancer by only 1-2%.

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.

BACKGROUND AND OBJECTIVES: Experimentally elevated potassium causes a clear pattern of electrocardiographic changes, but, clinically, the reliability of this pattern is unclear. Case reports suggest patients with renal insufficiency may have no electrocardiographic changes despite markedly elevated serum potassium. In a prospective series, 46% of patients with hyperkalemia were noted to have electrocardiographic changes, but no clear criteria were presented. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Charts were reviewed for patients who were admitted to a community-based hospital with a diagnosis of hyperkalemia. Inclusion criteria were potassium >/=6 with a concurrent electrocardiogram. Data were abstracted regarding comorbid diagnoses, medications, and treatment. Potassium concentrations were documented along with other electrolytes, pH, creatinine, and biomarkers of cardiac injury. Coincident, baseline, and follow-up electrocardiograms were examined for quantitative and qualitative changes in the QRS and T waves as well as the official cardiology readings. RESULTS: Ninety patients met criteria; two thirds were older than 65, and 48% presented with renal failure. Common medications included beta blockers, insulin, and aspirin; 80% had potassium <7.2. The electrocardiogram was insensitive for diagnosing hyperkalemia. Quantitative assessments of T-wave amplitude corroborated subjective assessments of T-wave peaking; however, no diagnostic threshold could be established. The probability of electrocardiographic changes increased with increasing potassium. The correlation between readers was moderate. CONCLUSIONS: Given the poor sensitivity and specificity of electrocardiogram changes, there is no support for their use in guiding treatment of stable patients. Without identifiable electrocardiographic markers of the risk for complications, management of hyperkalemia should be guided by the clinical scenario and serial potassium measurements.

OBJECTIVE: To provide evidence-based recommendations and expert guidance for the management of antineutrophil cytoplasmic antibody-associated vasculitis (AAV), including granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). METHODS: Clinical questions regarding the treatment and management of AAV were developed in the population, intervention, comparator, and outcome (PICO) format (47 for GPA/MPA, 34 for EGPA). Systematic literature reviews were conducted for each PICO question. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to assess the quality of evidence and formulate recommendations. Each recommendation required ≥70% consensus among the Voting Panel. RESULTS: We present 26 recommendations and 5 ungraded position statements for GPA/MPA, and 15 recommendations and 5 ungraded position statements for EGPA. This guideline provides recommendations for remission induction and maintenance therapy as well as adjunctive treatment strategies in GPA, MPA, and EGPA. These recommendations include the use of rituximab for remission induction and maintenance in severe GPA and MPA and the use of mepolizumab in nonsevere EGPA. All recommendations are conditional due in part to the lack of multiple randomized controlled trials and/or low-quality evidence supporting the recommendations. CONCLUSION: This guideline presents the first recommendations endorsed by the American College of Rheumatology and the Vasculitis Foundation for the management of AAV and provides guidance to health care professionals on how to treat these diseases.

OBJECTIVES: Spontaneous pneumomediastinum (SPM) is an uncommon, benign, self-limited disorder that usually occurs in young adults without any apparent precipitating factor or disease. The purpose of this study was to review our experience in dealing with this entity and detail a reasonable course of assessment and management. METHODS: A retrospective case series was conducted to identify adult patients with SPM who were diagnosed and treated in a single institution between 1993 and 2000. RESULTS: Twenty-four patients were identified who included 18 men and 6 women with a mean age of 17.5 years. Acute onset chest pain was the predominant symptom at presentation. Only half of the patients developed clinically evident subcutaneous emphysema. The most frequent precipitating factor was a history of illegal drug abuse seen in 25% of patients. Other factors included asthmatic bronchospasm, physical activity and violent coughing or vomiting. Chest radiography and computerized tomography (CT) were diagnostic in all cases with CT scan revealing six cases with associated pulmonary abnormalities. Esophagogram and flexible bronchoscopy were selectively used. Twelve patients (50%) were admitted to the hospital. Their mean hospital stay was 2 days. All patients were conservatively treated. In a follow-up of 3-10 years no complications or recurrences were observed. CONCLUSIONS: SPM follows alveolar rupture in the pulmonary interstitium. It shows a rising incidence in young drug users. It has a wide range of clinical features necessitating a high index of suspicion. Chest X-ray and CT scan should be always performed. Hospitalization and aggressive approach should be limited. SPM responds well to conservative treatment and follows a benign natural course.

BACKGROUND: Clinical reads of coronary computed tomography angiography (CTA), especially by less experienced readers, may result in overestimation of coronary artery disease stenosis severity compared with expert interpretation. Artificial intelligence (AI)-based solutions applied to coronary CTA may overcome these limitations. OBJECTIVES: This study compared the performance for detection and grading of coronary stenoses using artificial intelligence-enabled quantitative coronary computed tomography (AI-QCT) angiography analyses to core lab-interpreted coronary CTA, core lab quantitative coronary angiography (QCA), and invasive fractional flow reserve (FFR). METHODS: Coronary CTA, FFR, and QCA data from 303 stable patients (64 ± 10 years of age, 71% male) from the CREDENCE (Computed TomogRaphic Evaluation of Atherosclerotic DEtermiNants of Myocardial IsChEmia) trial were retrospectively analyzed using an Food and Drug Administration-cleared cloud-based software that performs AI-enabled coronary segmentation, lumen and vessel wall determination, plaque quantification and characterization, and stenosis determination. RESULTS: Disease prevalence was high, with 32.0%, 35.0%, 21.0%, and 13.0% demonstrating ≥50% stenosis in 0, 1, 2, and 3 coronary vessel territories, respectively. Average AI-QCT analysis time was 10.3 ± 2.7 minutes. AI-QCT evaluation demonstrated per-patient sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 94%, 68%, 81%, 90%, and 84%, respectively, for ≥50% stenosis, and of 94%, 82%, 69%, 97%, and 86%, respectively, for detection of ≥70% stenosis. There was high correlation between stenosis detected on AI-QCT evaluation vs QCA on a per-vessel and per-patient basis (intraclass correlation coefficient = 0.73 and 0.73, respectively; P < 0.001 for both). False positive AI-QCT findings were noted in in 62 of 848 (7.3%) vessels (stenosis of ≥70% by AI-QCT and QCA of <70%); however, 41 (66.1%) of these had an FFR of <0.8. CONCLUSIONS: A novel AI-based evaluation of coronary CTA enables rapid and accurate identification and exclusion of high-grade stenosis and with close agreement to blinded, core lab-interpreted quantitative coronary angiography. (Computed TomogRaphic Evaluation of Atherosclerotic DEtermiNants of Myocardial IsChEmia [CREDENCE]; NCT02173275).

The anatomic description of the extent of tumor spread (tumor staging) assists clinical management, facilitates communication among physicians, is an essential part of randomized controlled trials, and may help in the counseling patients and their families. However, in recent years, additional "prognostic factors" have been defined, many of which assess or reflect the biologic behavior of malignant neoplasms. Other measures of tumor biochemistry address the natural history of neoplastic development and often are included in a discussion of new prognostic factors. This review article summarizes current knowledge and thinking related to tumor prognostic factors in four areas by providing: (1) a definition and principles of anatomic spread of tumor (staging) and some suggestions for improvement, (2) a description of some examples of additional factors of prognostic significance, (3) some statistical methods to evaluate prognostic factors, and (4) an examination of the possible future of summary statements of outcome (i.e., prognostic indexes).

A boy with metastatic and fatal chondroblastoma is presented. Unlike previously published examples of metastatic chondroblastoma, these metastases developed before any operative manipulation of the primary tumor. The histologic characteristics of the primary, metastatic, and locally recurrent tumors were those of a conventional chondroblastoma. A review of published cases of atypical, aggressive, and malignant chondroblastoma is presented with current follow-up information. Although some metastatic chondroblastomas may result from operative manipulation of the primary tumor and are clinically benign, other histologically benign chondroblastomas exist that are capable of pursuing a malignant course. The authors designate these as malignant chondroblastomas. No histologic criteria exist for the separation of these tumors.

Abstract Determining the amount of human DNA extracted from a crime scene sample is an important step in DNA profiling. The forensic community relies almost entirely upon a technique (slot blot) to quantitate human DNA that is imprecise, time consuming, and labor intensive. We have previously described a method for quantitation of human DNA based on PCR amplification of a repetitive Alu sequence that uses a fluorescence plate reader. This manuscript describes and validates a variation of this assay using real-time PCR and SYBR® Green I for quantitation. The advantages of the real-time assay over the plate reader assay are: reduced hands-on time, lower assay cost, and a greater dynamic range. The main disadvantage is the cost of the real-time instrument. However, for those forensic laboratories with access to a real-time instrument, this Alu-based assay has a dynamic range of 16 ng to 1 pg, is sensitive, specific, fast, quantitative, and uses only 2 µL of sample.

Treatment with buserelin, an agonist of luteinising hormone releasing hormone, and human menopausal gonadotrophin was compared with the conventional treatment of clomiphene citrate and human menopausal gonadotrophin in the outcome of in vitro fertilisation. Seventy seven infertile women had 83 cycles of treatment with buserelin and human menopausal gonadotrophin, and concurrently another 328 infertile women were treated with clomiphene citrate and human menopausal gonadotrophin. Seven (8%) cycles were cancelled owing to inadequate super-ovulation or ovarian hyperstimulation in the women receiving buserelin and 103 (31%) were cancelled because of poor follicular development in those receiving clomiphene citrate. The mean number of oocytes recovered was significantly higher with buserelin (9.5 (SD 4.5) v 5.5 (2.2)) as was the mean number of embryos obtained (4.3 (2.4) v 2.9 (1.7)). Significantly more women who had an embryo transfer became clinically pregnant after treatment with buserelin (53% (30/57) v 30% (48/159), or 36% v 14% of treatment cycles). Altogether 33% (10) of pregnancies in women treated with buserelin were multiple compared with 23% (11) in those treated conventionally. Of the 17 completed pregnancies in women treated with buserelin, 11 resulted in the birth of live babies (eight singletons, two sets of twins, and one set of triplets) and six failed, five before 12 weeks' gestation and one at 22 weeks. The 13 continuing pregnancies (32 weeks) were eight singletons, two sets of twins, and three sets of triplets. Of the 48 completed pregnancies in women treated with clomiphene citrate, 35 resulted in the birth of live babies (26 singletons, five sets of twins and four sets of triplets) and 13 failed, eleven before 12 weeks' gestation and two by 27 weeks. Buserelin increased the chance of pregnancy after in vitro fertilisation compared with conventional treatment, but the risk of multiple pregnancy may be increased.

Gastrointestinal (GI) fistulas allow abnormal diversions of GI contents, digestive juices, water, electrolytes, and nutrients from one hollow viscus to another or to the skin, potentially precipitating a wide variety of pathophysiologic effects. Mortality rates have decreased significantly during the past few decades from as high as 40% to 65% to 5.3% to 21.3% largely as a result of advances in intensive care, nutritional support, antimicrobial therapy, wound care, and operative techniques. The primary causes of death secondary to enterocutaneous fistulas have been, and continue to be, malnutrition, electrolyte imbalances, and sepsis, especially in high-output fistulas, which continue to have a mortality rate of about 35%. Priorities in the management of GI fistulas include restoration of blood volume and correction of fluid, electrolyte, and acid-base imbalances; control of infection and sepsis with appropriate antibiotics and drainage of abscesses; initiation of GI tract rest including secretory inhibition and nasogastric suction; control and collection of fistula drainage with protection of the surrounding skin; and provision of optimal nutrition by total parenteral nutrition (TPN) or enteral nutrition (EN) (or both). The role of nutrition support in the management of enterocutaneous fistulas as either TPN or EN is primarily one of supportive care to prevent malnutrition, thereby obviating further deterioration of an already debilitated patient. It has been shown in several studies that TPN has substantially improved the prognosis of GI fistula patients by increasing the rate of spontaneous closure and improving the nutritional status of patients requiring repeat operations. Moreover, other studies have shown that nutritional support decreases or modifies the composition of the GI tract secretions and is thus considered to have a primary therapeutic role in the management of fistula patients. Finally, if a fistula has not closed within 30 to 40 days, or if it is unlikely to close because of a variety of collateral or compounding pathophysiologic conditions, consideration must be given to operative resection of the fistula while continuing to maintain the previous nutritional and metabolic support. The morbidity and mortality rates in such unfortunate patients remain high despite the many recent advances in surgical and metabolic technology.

377 Background: Neoadjuvant therapy has been associated with a median overall survival (OS) of 18 – 23 months (mo) in patients (pts) with BR pancreatic ductal adenocarcinoma (PDAC). To establish reference regimens to which novel treatments can be compared in future studies, we evaluated neoadjuvant mFOLFIRINOX with or without RT in BR PDAC in a phase II National Clinical Trials Network (NCTN) trial. Methods: Pts with ECOG PS 0-1 and BR PDAC confirmed by central real-time radiographic review after pre-registration were randomized to either arm A: 8 cycles of neoadjuvant mFOLFIRINOX (oxaliplatin 85 mg/m 2 , irinotecan 180 mg/m 2 , leucovorin 400 mg/m 2 and infusional 5-fluorouracil 2400 mg/m 2 over 46 hours), or arm B: 7 cycles of mFOLFIRINOX followed by stereotactic body RT (SBRT, 33-40 Gy in 5 fractions [fx]) or hypofractionated image guided RT (HIGRT, 25 Gy in 5 fx). Pts in either arm without disease progression underwent pancreatectomy, then 4 cycles of adjuvant mFOLFOX6 (oxaliplatin 85 mg/m 2 , leucovorin 400 mg/m 2 and infusional 5-fluorouracil 2400 mg/m 2 over 46 hours). The primary endpoint, 18-mo OS rate, of each arm was compared to a historical control of 50%. Planned interim analysis mandated closure of either arm in which &lt;11 of first 30 accrued pts underwent R0 resection. Results: 155 pts pre-registered and 126 pts were enrolled to arm A (N=70; 54 randomized, 16 following closure of arm B) or arm B (N=56; closed at interim analysis, all pts randomized prior to closure). Median age (A: 63y, B: 67y), median CA 19-9 level (A: 171 U/ml, B: 248 U/ml) and ECOG PS (A: 51% PS 0, B: 57% PS 0) of registered pts were similar between arms (p &gt; 0.05). Treatment detailed in Table. The 18-mo OS rate based on Kaplan Meier estimates was 67.9% (95%CI: 54.6 – 78.0) in arm A and 47.3% (95%CI: 33.7 – 59.7) in arm B. Among pts who underwent pancreatectomy, 18-mo OS rate was 93.1% (95%CI: 84.3 – 100) and 78.9% (95%CI: 62.6 – 99.6) in arm A and B, respectively. With median follow-up of 27 and 31 mo, median OS was 31.0 (95%CI: 22.2 – NE) mo and 17.1 (95%CI: 12.8 – 24.4) mo in arm A and B, respectively. Conclusions: Neoadjuvant mFOLFIRINOX was associated with favorable OS relative to historical data in pts with BL PDAC in this phase II NCTN trial. mFOLFIRINOX with hypofractionated RT did not improve OS compared to historical data. mFOLFIRINOX represents a reference regimen in this setting and a backbone on which to add novel agents. Support: U10CA180821, U10CA180882, U24CA196171; https://acknowledgments.alliancefound.org Clinical trial information: NCT02839343. [Table: see text]

Nutritional support of surgical and critically ill patients has undergone significant advances since 1936 when Studley demonstrated a direct relationship between pre-operative weight loss and operative mortality. The advent of total parenteral nutrition followed by the extraordinary progress in parenteral and enteral feedings, in addition to the increased knowledge of cellular biology and biochemistry, have allowed clinicians to treat malnutrition and improve surgical patient's outcomes. We reviewed the literature for the current status of perioperative nutrition comparing parenteral nutrition with enteral nutrition. In a surgical patient with established malnutrition, nutritional support should begin at least 7-10 days prior to surgery. Those patients in whom eating is not anticipated beyond the first five days following surgery should receive the benefits of early enteral or parenteral feeding depending on whether the gut can be used. Compared to parenteral nutrition, enteral nutrition is associated with fewer complications, a decrease in the length of hospital stay, and a favorable cost-benefit analysis. In addition, many patients may benefit from newer enteral formulations such as Immunonutrition as well as disease-specific formulations.

OBJECTIVE: To provide evidence-based recommendations and expert guidance for the management of giant cell arteritis (GCA) and Takayasu arteritis (TAK) as exemplars of large vessel vasculitis. METHODS: Clinical questions regarding diagnostic testing, treatment, and management were developed in the population, intervention, comparator, and outcome (PICO) format for GCA and TAK (27 for GCA, 27 for TAK). Systematic literature reviews were conducted for each PICO question. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to rate the quality of the evidence. Recommendations were developed by the Voting Panel, comprising adult and pediatric rheumatologists and patients. Each recommendation required ≥70% consensus among the Voting Panel. RESULTS: We present 22 recommendations and 2 ungraded position statements for GCA, and 20 recommendations and 1 ungraded position statement for TAK. These recommendations and statements address clinical questions relating to the use of diagnostic testing, including imaging, treatments, and surgical interventions in GCA and TAK. Recommendations for GCA include support for the use of glucocorticoid-sparing immunosuppressive agents and the use of imaging to identify large vessel involvement. Recommendations for TAK include the use of nonglucocorticoid immunosuppressive agents with glucocorticoids as initial therapy. There were only 2 strong recommendations; the remaining recommendations were conditional due to the low quality of evidence available for most PICO questions. CONCLUSION: These recommendations provide guidance regarding the evaluation and management of patients with GCA and TAK, including diagnostic strategies, use of pharmacologic agents, and surgical interventions.

We conducted this systematic review, one of four related to productive aging, to explore the existing evidence for the health benefits of engagement in occupations and activities among older adults. The review incorporates the breadth of areas of occupation in which older adults engage and the range of health benefits derived from that engagement. The results of this review demonstrate the multidisciplinary appreciation for occupational engagement and associated well-being and elucidate the health effects of engagement in a wide variety of occupations and activities. Additionally, the results of this systematic review support occupational therapy's historical ideologies and core philosophies linking occupational engagement to improved health and well-being. The findings suggest an increasing role for occupational therapy service delivery in community-based health promotion and prevention efforts to meet the everyday activity and health needs of the growing older adult population.