Stratification of Fusobacterium nucleatum by local health status in the oral cavity defines its subspecies disease association.

The ubiquitous inflammophilic oral pathobiont Fusobacterium nucleatum (Fn) is widely recognized for its strong association with inflammatory dysbiotic diseases and cancer. Fn is subdivided into four subspecies, which are historically considered functionally interchangeable in the oral cavity. To test this assumption, we analyzed patient-matched dental plaque and odontogenic abscess clinical specimens and examined whether an inflammatory environment selects for/against particular Fn subspecies. Dental plaque harbored a greater diversity of fusobacteria, with Fn. polymorphum dominating, whereas odontogenic abscesses were exceptionally biased for the largely uncharacterized organism Fn. animalis. Comparative genomic analyses revealed significant genotypic distinctions among Fn subspecies that correlate with their preferred ecological niches and support a taxonomic reassignment of each as a distinct Fusobacterium species. Despite originating as a low-abundance organism in dental plaque, Fn. animalis typically outcompetes other oral fusobacteria within the inflammatory abscess environment, which may explain its prevalence in other oral and extraoral diseases.

Contemporary Outcomes of Transduodenal Sphincteroplasty: the Importance of Surgical Quality.

BACKGROUND: Sphincter of Oddi dysfunction (SOD) is managed primarily by endoscopic sphincterotomy (ES); however, surgical transduodenal sphincteroplasty (TDS) is a treatment option for select patients. In our high-volume pancreatico-biliary practice, we have observed variable outcomes among TDS patients; therefore, we sought to determine preoperative predictors of durable improvement in quality of life. METHODS: SOD patients treated by TDS between January 2006 and December 2015 were studied. The primary outcome measure was long-term changes in quality of life after sphincteroplasty. The secondary outcome measure examined postoperative outcomes, including postoperative complications, need for repeat procedures, and readmission rates. Perioperative data were abstracted, and the SF-36 quality-of-life (QoL) survey was administered. Standard statistical analysis included non-parametric methods to examine bivariate associations. RESULTS: Eighty-eight patients had an average follow-up duration of 6.7 (± 2.9) years. Thirty (34%) patients were naïve to endoscopic therapy. Patients with prior endoscopy averaged 2.1 procedures (range 1 to 13) prior to surgery. Perioperative morbidity was 27%; one postoperative death was caused by severe acute pancreatitis. Twenty-nine (33%) patients required subsequent biliary-pancreatic procedures. QoL analysis from available patients showed that 66% were improved or much improved. With multivariable analysis including SOD type and prior endoscopic instrumentation, freedom from surgical complication was the only variable that correlated significantly with a good outcome (p < 0.02). CONCLUSION: Surgical transduodenal sphincteroplasty provides durable symptom management for select patients with sphincter of Oddi dysfunction. Minimizing surgical complications optimizes long-term outcomes.

Prostate-Specific Antigen Response to Androgen Deprivation Therapy in the Neoadjuvant Setting for High-Risk Prostate Adenocarcinoma (PIRANHA): Pooled Analysis of Two Randomized Clinical Trials.

PURPOSE: A suboptimal prostate-specific antigen (PSA) response to neoadjuvant androgen deprivation therapy (ADT) among men who go on to receive definitive radiation therapy for prostate cancer might suggest the existence of castration-resistant disease or altered androgen receptor signaling. This in turn may portend worse long-term clinical outcomes, especially in men with high-risk disease. We set out to evaluate the prognostic impact of poor PSA response to neoadjuvant ADT in men with high-risk prostate cancer. METHODS AND MATERIALS: This was a post hoc analysis of the multicenter TROG 03.04 RADAR and PCS IV randomized clinical trials. Inclusion criteria for this analysis were patients with high-risk prostate cancer (defined as Gleason score ≥8, initial PSA ≥20 ng/mL, or cT3a disease or higher) who received definitive radiation therapy, at least 18 months of ADT, and had a preradiation therapy PSA level drawn after at least 3 months of neoadjuvant ADT. Poor PSA response was defined as PSA >0.5 ng/mL. Cox regression and Fine-Gray models were used to test whether poor PSA response was associated with metastasis-free survival, biochemical recurrence, prostate-cancer specific mortality, and overall survival. RESULTS: Nine hundred thirty men met inclusion criteria for this analysis. Median follow-up was 130 months (interquartile range [IQR], 89-154 months). After a median of 3 months (IQR, 3-4.2 months) of neoadjuvant ADT, the median PSA was 0.60 ng/mL (IQR, 0.29-1.59). Overall, 535 men (57%) had a PSA >0.5 ng/mL. Poor PSA response was associated with significantly worse metastasis-free survival (hazard ratio [HR], 3.93; P = .02), worse biochemical recurrence (subdistribution HR, 2.39; P = .003), worse prostate-cancer specific mortality (subdistribution HR, 1.50; P = .005), and worse overall survival (HR, 4.51; P = .05). CONCLUSIONS: Patients with PSA >0.5 mg/mL after at least 3 months of neoadjuvant ADT had worse long-term clinical outcomes and should be considered for treatment intensification.

The prevalence of Fusobacterium nucleatum subspecies in the oral cavity stratifies by local health status.

The ubiquitous inflammophilic pathobiont Fusobacterium nucleatum is widely recognized for its strong association with a variety of human dysbiotic diseases such as periodontitis and oral/extraoral abscesses, as well as multiple types of cancer. F. nucleatum is currently subdivided into four subspecies: F. nucleatum subspecies nucleatum (Fn. nucleatum), animalis (Fn. animalis), polymorphum (Fn. polymorphum), and vincentii/fusiforme (Fn. vincentii). Although these subspecies have been historically considered as functionally interchangeable in the oral cavity, direct clinical evidence is largely lacking for this assertion. Consequently, we assembled a collection of oral clinical specimens to determine whether F. nucleatum subspecies prevalence in the oral cavity stratifies by local oral health status. Patient-matched clinical specimens of both disease-free dental plaque and odontogenic abscess were analyzed with newly developed culture-dependent and culture-independent approaches using 44 and 60 oral biofilm/tooth abscess paired specimens, respectively. Most oral cavities were found to simultaneously harbor multiple F. nucleatum subspecies, with a greater diversity present within dental plaque compared to abscesses. In dental plaque, Fn. polymorphum is clearly the dominant organism, but this changes dramatically within odontogenic abscesses where Fn. animalis is heavily favored over all other fusobacteria. Surprisingly, the most commonly studied F. nucleatum subspecies, Fn. nucleatum, is only a minor constituent in the oral cavity. To gain further insights into the genetic basis for these phenotypes, we subsequently performed pangenome, phylogenetic, and functional enrichment analyses of oral fusobacterial genomes using the Anvi'o platform, which revealed significant genotypic distinctions among F. nucleatum subspecies. Accordingly, our results strongly support a taxonomic reassignment of each F. nucleatum subspecies into distinct Fusobacterium species. Of these, Fn. animalis should be considered as the most clinically relevant at sites of active inflammation, despite being among the least characterized oral fusobacteria.

Transgastric pancreatic necrosectomy: Tricks of the trade.

Necrotizing pancreatitis (NP) affects 20 % of the 300,000 patients diagnosed with acute pancreatitis every year. Mechanical intervention to debride necrotic and/or infected pancreatic and peripancreatic tissue is frequently required. Minimally invasive approaches to treat pancreatic necrosis have gained popularity over the last two decades, including transgastric pancreatic necrosectomy. The purpose of this report is to review the indications, surgical technique, advantages, and limitations of surgical transgastric necrosectomy.

Addition of Metastasis-Directed Therapy to Intermittent Hormone Therapy for Oligometastatic Prostate Cancer: The EXTEND Phase 2 Randomized Clinical Trial.

Importance: Despite evidence demonstrating an overall survival benefit with up-front hormone therapy in addition to established synergy between hormone therapy and radiation, the addition of metastasis-directed therapy (MDT) to hormone therapy for oligometastatic prostate cancer, to date, has not been evaluated in a randomized clinical trial. Objective: To determine in men with oligometastatic prostate cancer whether the addition of MDT to intermittent hormone therapy improves oncologic outcomes and preserves time with eugonadal testosterone compared with intermittent hormone therapy alone. Design, Setting, Participants: The External Beam Radiation to Eliminate Nominal Metastatic Disease (EXTEND) trial is a phase 2, basket randomized clinical trial for multiple solid tumors testing the addition of MDT to standard-of-care systemic therapy. Men aged 18 years or older with oligometastatic prostate cancer who had 5 or fewer metastases and were treated with hormone therapy for 2 or more months were enrolled to the prostate intermittent hormone therapy basket at multicenter tertiary cancer centers from September 2018 to November 2020. The cutoff date for the primary analysis was January 7, 2022. Interventions: Patients were randomized 1:1 to MDT, consisting of definitive radiation therapy to all sites of disease and intermittent hormone therapy (combined therapy arm; n = 43) or to hormone therapy only (n = 44). A planned break in hormone therapy occurred 6 months after enrollment, after which hormone therapy was withheld until progression. Main Outcomes and Measures: The primary end point was disease progression, defined as death or radiographic, clinical, or biochemical progression. A key predefined secondary end point was eugonadal progression-free survival (PFS), defined as the time from achieving a eugonadal testosterone level (≥150 ng/dL; to convert to nanomoles per liter, multiply by 0.0347) until progression. Exploratory measures included quality of life and systemic immune evaluation using flow cytometry and T-cell receptor sequencing. Results: The study included 87 men (median age, 67 years [IQR, 63-72 years]). Median follow-up was 22.0 months (range, 11.6-39.2 months). Progression-free survival was improved in the combined therapy arm (median not reached) compared with the hormone therapy only arm (median, 15.8 months; 95% CI, 13.6-21.2 months) (hazard ratio, 0.25; 95% CI, 0.12-0.55; P < .001). Eugonadal PFS was also improved with MDT (median not reached) compared with the hormone therapy only (6.1 months; 95% CI, 3.7 months to not estimable) (hazard ratio, 0.32; 95% CI, 0.11-0.91; P = .03). Flow cytometry and T-cell receptor sequencing demonstrated increased markers of T-cell activation, proliferation, and clonal expansion limited to the combined therapy arm. Conclusions and Relevance: In this randomized clinical trial, PFS and eugonadal PFS were significantly improved with combination treatment compared with hormone treatment only in men with oligometastatic prostate cancer. Combination of MDT with intermittent hormone therapy may allow for excellent disease control while facilitating prolonged eugonadal testosterone intervals. Trial Registration: ClinicalTrials.gov Identifier: NCT03599765.

Definitive local therapy for T4 prostate cancer associated with improved local control and survival.

OBJECTIVES: To evaluate patients with clinical (c)T4 prostate cancer (PCa), which represent both a heterogenous and understudied population, who often present with locally advanced disease and obstructive symptoms causing significant morbidity and mortality. We analysed whether receiving definitive local therapy influenced symptomatic and oncological outcomes. METHODS: Retrospective analysis of 154 patients with cT4 PCa treated at a single institution in 1996-2020. Systemic therapy with or without local treatment (surgery, radiotherapy [RT], or both). Uni- and multivariate analyses of associations between clinicopathological features (including obstructive symptoms) and receipt of local therapy on overall survival (OS) and disease control were done with Cox regression. RESULTS: The median follow-up time was 5.9 years. Most patients had adenocarcinoma (88%), Gleason score 9-10 (77%), and median baseline prostate-specific antigen (PSA) of 20 ng/mL; most (54%) had metastatic cT4N0-1M1 disease; 24% regionally advanced cT4N1M0, and 22% localised cT4N0M0. Local therapies were RT (n = 44), surgery (n = 28), or both (n = nine). Local therapy was associated with improved OS (hazard ratio [HR] 0.3, P < 0.001), longer freedom from local recurrence (HR 0.39, P = 0.002), less local progression (HR 0.41, P = 0.02), fewer obstructive symptoms with progression (HR 0.31, P = 0.01), and less death from local disease (HR 0.25, P = 0.002). On multivariate, local therapy was associated with improved survival (HR 0.58, P = 0.02), and metastatic disease (HR 2.93, P < 0.001) or high-risk pathology (HR 2.05, P = 0.03) was associated with worse survival. CONCLUSION: Definitive local therapy for cT4 PCa was associated with improved symptomatic outcomes and survival even among men with metastatic disease. Pending prospective evaluation, these findings support definitive treatment with local therapy for cT4 disease in select cases.

Neoadjuvant therapy at local versus outside institutions does not adversely impact surgical timing or long-term outcomes in patients with pancreatic adenocarcinoma.

BACKGROUND: Although high-volume centers are known to have better surgical outcomes, patients with pancreatic adenocarcinoma often receive chemotherapy at treatment centers closer to home. This study aimed to determine whether treatment site of neoadjuvant therapy relative to surgery location impacts surgical timing and long-term outcomes. METHODS: All patients with pancreatic adenocarcinoma who underwent oncologic resection at a single, high-volume institution between January 2016 and February 2020 and had neoadjuvant chemotherapy before surgery were queried from a prospectively maintained database. Patients were sorted based on location of neoadjuvant chemotherapy. RESULTS: A total of 179 patients were included in the study. Seventy-four (41.3%) patients received neoadjuvant chemotherapy at the same institution as their surgery (group A), 20 (11.2%) received chemotherapy outside of their surgical institution but within the same hospital/healthcare system (group B), and 85 (47.5%) received chemotherapy at an outside location (group C). The time from completion of neoadjuvant therapy to surgery was not significantly different between groups (A vs B vs C median [interquartile range]: 34.5 [14] vs 41.5 [24] vs 36 [22] days, P = .08). Thirty-day readmission rate was lower in group A (n (%): 1 (1.4%) vs 2 (10.0%) vs 11 (12.9%), P = .02). However, the 90-day mortality and overall survival did not differ significantly between groups. CONCLUSION: Patients may receive neoadjuvant therapy at local centers without impacting surgical scheduling. Although these patients may experience higher postoperative readmission rates, perioperative mortality and long-term survival are not adversely affected by location of chemotherapy. Multidisciplinary care can be effectively practiced in different locations without affecting overall outcomes in patients with pancreatic adenocarcinoma.

Readmission in acute pancreatitis: Etiology, risk factors, and opportunities for improvement.

Acute pancreatitis is associated with a readmission rate ranging from 7 to 34%. Readmission rates are highest among biliary (4-37%) and alcohol-induced (2-60%) acute pancreatitis. Severe acute pancreatitis and necrotizing pancreatitis have readmission rates ranging from 20 to 75%. The most common causes of readmission include recurrent acute pancreatitis (17-45% of readmissions) and smoldering symptoms/local complications (17-38%). A number of risk scores reliably estimate risk of readmission in acute pancreatitis. Decreased rates of readmission were reported in patients that underwent same-admission cholecystectomy in biliary pancreatitis and alcohol cessation interventions in alcohol-induced pancreatitis. This review article discusses readmission in acute pancreatitis, including etiology, risk factors, and opportunities for improved patient care.

Pancreatitis associated anxiety, depression, and stress: Hypothesis, definition, and intervention.

Necrotizing pancreatitis is characterized by a prolonged disease course requiring frequent hospitalization and intervention. Necrotizing pancreatitis patients have high rates of intensive care unit admission and organ failure. Critical illness is an identified risk factor for the development of anxiety, depression, and posttraumatic stress disorder. Limited literature examines quality of life in necrotizing pancreatitis patients, and studies examining psychiatric sequalae of necrotizing pancreatitis including depression, anxiety, and posttraumatic stress disorder are virtually nonexistent. Here, we review critical literature examining risk factors for poor mental health outcomes during and after necrotizing pancreatitis, identify several screening instruments to quantify mental health outcomes, and propose an intervention to improve mental health outcomes in patients with necrotizing pancreatitis. We conclude that establishing the incidence of mental health disorders and implementing strategies to improve mental health outcomes are critical to holistic care of necrotizing pancreatitis patients.

Obesity Worsens Local and Systemic Complications of Necrotizing Pancreatitis and Prolongs Disease Course.

BACKGROUND: Obesity is epidemic in the USA. Limited data exist examining obesity's influence on necrotizing pancreatitis (NP) disease course. METHODS: Retrospective review of prospectively maintained database of 571 adult necrotizing pancreatitis patients treated between 2007 and 2018. Patients were grouped according to body mass index (BMI) at disease onset. Patient characteristics, necrotizing pancreatitis course, and outcomes were compared between non-obese (BMI < 30) and obese (BMI > 30) patients. RESULTS: Among 536 patients with BMI data available, 304 (57%) were obese (BMI > 30), and 232 (43%) were non-obese (BMI < 30). NP etiology in the obese group was more commonly biliary (55% versus 46%, p = 0.04) or secondary to hypertriglyceridemia (10% versus 2%, p < 0.001) and less commonly alcohol (17% versus 26%, p = 0.01). Obese patients had a higher incidence of baseline comorbid disease. The CT severity index was similar between groups though obese patients had a higher rate of > 50% pancreatic gland necrosis (27% versus 19%, p = 0.02). The rates of infected necrosis and organ failure were higher among obese patients. Percutaneous drainage was more common in obese patients. Time to first necrosis intervention was earlier with increasing BMI. NP disease duration was longer in obese patients. The overall mortality rate of non-obese and obese patients did not differ. However, mortality rate increased with increasing BMI. CONCLUSION: Necrotizing pancreatitis in obese patients is characterized by a prolonged disease course, a higher risk of organ failure, infected necrosis, and the need for early necrosis-related intervention. Mortality increases with increasing BMI.

Development of the First Tractable Genetic System for Parvimonas micra, a Ubiquitous Pathobiont in Human Dysbiotic Disease.

Parvimonas micra is a Gram-positive obligate anaerobe and a typical member of the human microbiome. P. micra is among the most highly enriched species at numerous sites of mucosal dysbiotic disease and is closely associated with the development of multiple types of malignant tumors. Despite its strong association with disease, surprisingly little is known about P. micra pathobiology, which is directly attributable to its longstanding genetic intractability. To address this problem, we directly isolated a collection of P. micra strains from odontogenic abscess clinical specimens and then screened these isolates for natural competence. Amazingly, all of the P. micra clinical isolates exhibited various levels of natural competence, including the reference strain ATCC 33270. By exploiting this ability, we were able to employ cloning-independent methodologies to engineer and complement a variety of targeted chromosomal genetic mutations directly within low-passage-number clinical isolates. To develop a tractable genetic system for P. micra, we first adapted renilla-based bioluminescence for highly sensitive reporter studies. This reporter system was then applied for the development of the novel Theo+ theophylline-inducible riboswitch for tunable gene expression studies over a broad dynamic range. Finally, we demonstrate the feasibility of generating mariner-based transposon sequencing (Tn-seq) libraries for forward genetic screening in P. micra. With the availability of a highly efficient transformation protocol and the current suite of genetic tools, P. micra should now be considered a fully genetically tractable organism suitable for molecular genetic research. The methods presented here provide a clear path to investigate the understudied role of P. micra in polymicrobial infections and tumorigenesis. IMPORTANCE Parvimonas micra is among the most highly enriched species at numerous sites of mucosal dysbiotic disease and is closely associated with numerous cancers. Despite this, little is known about P. micra pathobiology, which is directly attributable to its longstanding genetic intractability. In this study, we provide the first report of P. micra natural competence and describe the only tractable genetic system for this species. The methods presented here will allow for the detailed study of P. micra and its role in infection and tumorigenesis.

Contemporary Intervention in Necrotizing Pancreatitis: Improved Understanding Changing Practice.

BACKGROUND: Treatment of necrotizing pancreatitis (NP) has shifted in favor of a minimally invasive step-up approach rather than early open pancreatic debridement. We hypothesized that this paradigm shift would be reflected in the intervention, morbidity, and mortality profile of NP patients. STUDY DESIGN: Single-institution retrospective review of 767 NP patients treated between 2005 and 2019. Two eras of NP intervention were identified relative to the introduction of a minimally invasive approach to NP. Patients treated between 2005 and 2010 were classified as the "early" group and compared with patients treated between 2011 and 2019, classified as the "late" group. RESULTS: In total, 299 NP patients comprised the early group and 468 patients comprised the late group. No differences were seen in patient demographics, comorbidity profile, or NP etiology between groups. Necrosis volume, necrosis location, CT severity index (CTSI), and rates of infected necrosis were similar between groups. No difference was seen in mortality. Mechanical intervention for NP was more common in the early than the late group (86% vs. 73%, p < 0.001). Time to first intervention was similar between groups (79 ± 7d vs. 75 ± 6d). The early group had higher rates of open pancreatic debridement (72% vs. 55%, p < 0.001). Endoscopic intervention was less common in the early than the late group (7% vs. 16%, p < 0.001). NP disease duration was longer in the early than the late group (223 ± 12d vs. 179 ± 7d, p = 0.001). CONCLUSION: Contemporary management of necrotizing pancreatitis is marked by less frequent operative debridement and shorter disease duration.

Early postoperative serum hyperamylasemia: Harbinger of morbidity hiding in plain sight?

BACKGROUND: The clinical significance of postoperative serum pancreatic enzyme elevation after pancreatoduodenectomy is understudied. We hypothesized that elevation in serum enzymes predicts morbidity and mortality after pancreatoduodenectomy. METHODS: Retrospective review of 677 patients who underwent pancreatoduodenectomy at a single institution from 2013 to 2019. Patients were categorized based on serum enzyme concentrations. Patient characteristics, drain amylase, and outcomes among groups were compared. RESULTS: In total, 415 of 677 patients had postoperative serum amylase concentrations measured. Of these, 243 (59%) were normal, 96 (23%) were classified as postoperative serum hyperamylasemia, and 76 (18%) were classified as postoperative acute pancreatitis. Major morbidity was lower among patients with normal enzyme concentration (10%) and higher in patients with postoperative serum hyperamylasemia (23%) and postoperative acute pancreatitis (18%) (P = .008). Patients with normal enzymes were less likely to develop postoperative pancreatic fistula (5%) compared with patients with postoperative serum hyperamylasemia (26%) and postoperative acute pancreatitis (21%) (P < .001) and less likely to develop delayed gastric emptying (9% vs 23% and 20%, respectively); P = .002. No difference in mortality was seen among groups. CONCLUSION: Elevated serum pancreatic enzyme concentration occurs frequently after pancreatoduodenectomy and is associated with increased postoperative morbidity. Serum enzyme concentration should be considered in management after pancreatoduodenectomy.

Outcomes in Endoscopic and Operative Transgastric Pancreatic Debridement.

OBJECTIVES: Select patients with anatomically favorable walled off pancreatic necrosis may be treated by endoscopic (Endo-TGD) or operative (OR-TGD) transgastric debridement (TGD). We compared our experience with these 2 approaches. SUMMARY BACKGROUND DATA: Select necrotizing pancreatitis (NP) patients are suitable for TGD which may be accomplished endoscopically or surgically. Limited experience exists contrasting these techniques exists. METHODS: Patients undergoing Endo-TGD and OR-TGD at a single, high-volume pancreatic center between 2008 and 2019 were identified from a prospective database. Patient characteristics, procedural details, and outcomes of these 2 groups were compared. RESULTS: Among 498 NP patients undergoing necrosis intervention, 160 (32%) had TGD: 59 Endo-TGD and 101 OR-TGD. The groups were statistically similar in age, comorbidity, pancreatitis etiology, necrosis anatomy, pancreatitis severity, and timing of TGD from pancreatitis insult. OR-TGD required 1.1 ±â€Š0.5 and Endo-TGD 3.0 ±â€Š2.0 debridements/patient. Fewer hospital readmissions and repeat necrosis interventions, and shorter total inpatient length of stay were observed in OR-TGD patients. New-onset organ failure [Endo-TGD (13%); OR-TGD (13%); P = 1.0] was similar between groups. Hospital length of stay after TGD was significantly longer in patients undergoing Endo-TGD (13.8 ±â€Š20.8 days) compared to OR-TGD (9.4 ±â€Š6.1 days; P = 0.047). Mortality was 7% in Endo-TGD and 1% in OR-TGD (P = 0.04). CONCLUSIONS: Operative and endoscopic transgastric debridement achieve necrosis resolution with different temporal and procedural profiles. Clear multidisciplinary communication is essential to determine appropriate approach to individual necrotizing pancreatitis patients.

Duodenal complications in necrotizing pancreatitis: Challenges of an overlooked complication.

BACKGROUND: Duodenal complications of necrotizing pancreatitis (NP) are challenging and understudied. We sought to characterize the demographics and clinical course of NP patients with duodenal complications. METHODS: Single institution retrospective review of 687 NP patients treated from 2005 to 2018. RESULTS: Duodenal complications developed in 40 (6%) patients including fistula in 11 (2%) and stricture in 29 (4%) patients. Patients with duodenal complications had increased computed tomography severity index (CTSI), degree of glandular necrosis, organ failure, infected necrosis, and disease duration. Mortality from NP was increased in patients with duodenal fistula (36%) compared to patients with duodenal stricture (7%) and patients without duodenal complications (9%). Surgical management of duodenal complications was required in 9/11 (82%) patients with fistula and 17/29 (59%) patients with stricture. CONCLUSIONS: Duodenal complications occurred in 6% of necrotizing pancreatitis patients. Sixty five percent of patients with duodenal complications required surgical correction. Duodenal fistula was associated with increased mortality.

Prospective Analysis of the Mechanisms Underlying Ineffective Deep Vein Thrombosis Prophylaxis in Necrotizing Pancreatitis.

BACKGROUND: Patients with necrotizing pancreatitis (NP) have the highest rate of venous thromboembolism (VTE) of any hospitalized patient (57%). We hypothesized that VTE prophylaxis might be inadequate in the setting of this profound inflammatory disease and that early detection of deep vein thrombosis would limit pulmonary embolism. STUDY DESIGN: All patients with NP treated at a single center between August 2018 and December 2019 were enrolled in prospective, weekly VTE screening, including 4-extremity duplex ultrasound. Routine chemoprophylaxis included low-molecular-weight or unfractionated heparin. Peak serum anti-factor Xa concentration was measured during weekly screening (goal prophylaxis 0.2 to 0.4 IU/mL). RESULTS: Eighty-five patients with NP underwent a total of 201 screening events (mean 2.4 per patient). VTE developed in 55 patients (65%), including splanchnic vein thrombosis in 41 patients (48%) and extremity deep vein thrombosis (eDVT) in 32 patients (38%). Extremity DVT was diagnosed a mean ± SD of 44 ± 30 days after NP onset. Symptomatic pulmonary embolism was prevented in all patients diagnosed with eDVT and no contraindication to anticoagulation (0 of 29). Prophylactic anti-factor Xa concentration was only achieved in 21% (12 of 57 screening events); no eDVTs developed in patients achieving prophylactic anti-factor Xa concentration. CONCLUSIONS: In patients with NP, identification of eDVT by screening ultrasound permits early treatment and prevents symptomatic pulmonary embolism. Fixed dosing of chemical prophylaxis is inadequate in most patients with NP and likely contributes to the mechanism of increased VTE in NP.

Should the femoral or brachial artery be used if radial artery cannulation is difficult?

Current best practice in placement of arterial lines is to attempt to cannulate the radial artery in the first instance. However, if the radial artery is difficult to cannulate there is no consensus among clinicians on how best to proceed. This article looks at the evidence for the different options.