Comparative analysis of persistence and remission with guselkumab versus secukinumab and ixekizumab in the United States.

Purpose: Real-world data comparing long-term performance of interleukin (IL)-23 and IL-17 inhibitors in psoriasis are limited. This study compared treatment persistence and remission among patients initiating guselkumab versus IL-17 inhibitors.Methods: Adults with psoriasis initiating guselkumab, secukinumab, or ixekizumab treatment (index date) were identified from Merative™ MarketScan® Research Databases (01/01/2016-10/31/2021). Persistence was defined as no index biologic supply gaps of twice the labeled maintenance dosing interval. Remission was defined using an exploratory approach as index biologic discontinuation for ≥6 months without psoriasis-related inpatient admissions and treatments.Results: There were 3516 and 6066 patients in the guselkumab versus secukinumab comparison, and 3805 and 4674 patients in guselkumab versus ixekizumab comparison. At 18 months, the guselkumab cohort demonstrated about twice the persistence rate as secukinumab (hazard ratio [HR] = 2.15; p < 0.001) and ixekizumab cohorts (HR = 1.77; p < 0.001). At 6 months after index biologic discontinuation, the guselkumab cohort was 31% and 40% more likely to achieve remission than secukinumab (rate ratio [RR] = 1.31; p < 0.001) and ixekizumab cohorts (RR = 1.40; p < 0.001).Conclusions: Guselkumab was associated with greater persistence and likelihood of remission than IL-17 inhibitors, indicating greater disease control and modification potential.

Genomic loci influence patterns of structural covariance in the human brain.

Normal and pathologic neurobiological processes influence brain morphology in coordinated ways that give rise to patterns of structural covariance (PSC) across brain regions and individuals during brain aging and diseases. The genetic underpinnings of these patterns remain largely unknown. We apply a stochastic multivariate factorization method to a diverse population of 50,699 individuals (12 studies and 130 sites) and derive data-driven, multi-scale PSCs of regional brain size. PSCs were significantly correlated with 915 genomic loci in the discovery set, 617 of which are newly identified, and 72% were independently replicated. Key pathways influencing PSCs involve reelin signaling, apoptosis, neurogenesis, and appendage development, while pathways of breast cancer indicate potential interplays between brain metastasis and PSCs associated with neurodegeneration and dementia. Using support vector machines, multi-scale PSCs effectively derive imaging signatures of several brain diseases. Our results elucidate genetic and biological underpinnings that influence structural covariance patterns in the human brain.

Mapping the Relationship of White Matter Lesions to Depression in Multiple Sclerosis.

BACKGROUND: Multiple sclerosis (MS) is an immune-mediated neurological disorder, and up to 50% of patients experience depression. We investigated how white matter network disruption is related to depression in MS. METHODS: Using electronic health records, 380 participants with MS were identified. Depressed individuals (MS+Depression group; n = 232) included persons who had an ICD-10 depression diagnosis, had a prescription for antidepressant medication, or screened positive via Patient Health Questionnaire (PHQ)-2 or PHQ-9. Age- and sex-matched nondepressed individuals with MS (MS-Depression group; n = 148) included persons who had no prior depression diagnosis, had no psychiatric medication prescriptions, and were asymptomatic on PHQ-2 or PHQ-9. Research-quality 3T structural magnetic resonance imaging was obtained as part of routine care. We first evaluated whether lesions were preferentially located within the depression network compared with other brain regions. Next, we examined if MS+Depression patients had greater lesion burden and if this was driven by lesions in the depression network. Primary outcome measures were the burden of lesions (e.g., impacted fascicles) within a network and across the brain. RESULTS: MS lesions preferentially affected fascicles within versus outside the depression network (ß = 0.09, 95% CI = 0.08 to 0.10, p < .001). MS+Depression patients had more lesion burden (ß = 0.06, 95% CI = 0.01 to 0.10, p = .015); this was driven by lesions within the depression network (ß = 0.02, 95% CI = 0.003 to 0.040, p = .020). CONCLUSIONS: We demonstrated that lesion location and burden may contribute to depression comorbidity in MS. MS lesions disproportionately impacted fascicles in the depression network. MS+Depression patients had more disease than MS-Depression patients, which was driven by disease within the depression network. Future studies relating lesion location to personalized depression interventions are warranted.

Amidine-Based Cationic Conjugated Oligoelectrolytes with Antimicrobial Activity against Pseudomonas aeruginosa Biofilms.

Pseudomonas aeruginosa is an opportunistic Gram-negative bacterium that can cause high-morbidity infections. Due to its robust, flexible genome and ability to form biofilms, it can evade and rapidly develop resistance to antibiotics. Cationic conjugated oligoelectrolytes (COEs) have emerged as a promising class of antimicrobials. Herein, we report a series of amidine-containing COEs with high selectivity for bacteria. From this series, we identified 1b as the most active compound against P. aeruginosa (minimum inhibitory concentration (MIC) = 2 µg/mL) with low cytotoxicity (IC50 (HepG2) = 1024 µg/mL). The activity of 1b was not affected by known drug-resistant phenotypes of 100 diverse P. aeruginosa isolates. Moreover, 1b is bactericidal with a low propensity for P. aeruginosa to develop resistance. Furthermore, 1b is also able to inhibit biofilm formation at subinhibitory concentrations and kills P. aeruginosa in established biofilms. The in vivo efficacy of 1b was demonstrated in biofilm-associated murine wound infection models.

Textbook outcome as a composite measure of quality in hepaticopancreatic surgery.

BACKGROUND: Textbook outcome (TO) is a valuable metric to assess postoperative outcomes. The aim of this study was to assess TO in patients undergoing hepatopancreatic surgery. METHODS: This was a retrospective cohort NSQIP study from 2015 to 2018. TOs are defined as no complication or mortality and length of stay within the 75th percentile. RESULTS: This study included 44 235 patients. Of those patients, 61% underwent pancreatic surgery (PS) and 39% hepatic surgery (HS). The most common surgical procedure was pancreaticoduodenectomy (16 464), followed by partial hepatectomy (11 817), distal pancreatectomy (8292), hemihepatectomy (4247), hepatic trisegmentectomy (1366) and total pancreatectomy (706). TO was more common for HS than PS, 47% versus 40%, p < .001. TO was more common for younger (0-65, OR: 1.60; CI: 1.30-1.96, p < .001), female (OR: 1.23; CI: 1.17-1.29, p < .001), white (OR: 1.10; CI: 1.01-1.19, p = .022), and lower ASA class (OR: 2.11; CI: 1.54-2.90, p < .001) patients. For patients undergoing HS TO was more common after partial lobectomy than trisegmentectomy and lobectomy (OR: 1.36; CI: 1.18-1.57, p < .001). For those undergoing PS, there was a lower likelihood of TO for those who are obese/morbidly obese compared to normal-weight patients (OR: 0.73; CI: 0.67-0.79, p < .001). Unlike HS, TO for patients undergoing PS was not associated with the type of surgical procedure. CONCLUSIONS: TO is a composite that can be applied to a national data set to analyze outcome quality. In HS, more complex surgical procedures are associated with a decreased likelihood of TO. In PS, TO are similar regardless of the procedure but less common in obese or morbidly obese patients.

Mapping the relationship of white matter lesions to depression in multiple sclerosis.

Importance: Multiple sclerosis (MS) is an immune-mediated neurological disorder that affects nearly one million people in the United States. Up to 50% of patients with MS experience depression. Objective: To investigate how white matter network disruption is related to depression in MS. Design: Retrospective case-control study of participants who received research-quality 3-tesla neuroimaging as part of MS clinical care from 2010-2018. Analyses were performed from May 1 to September 30, 2022. Setting: Single-center academic medical specialty MS clinic. Participants: Participants with MS were identified via the electronic health record (EHR). All participants were diagnosed by an MS specialist and completed research-quality MRI at 3T. After excluding participants with poor image quality, 783 were included. Inclusion in the depression group (MS+Depression) required either: 1) ICD-10 depression diagnosis (F32-F34.*); 2) prescription of antidepressant medication; or 3) screening positive via Patient Health Questionnaire-2 (PHQ-2) or -9 (PHQ-9). Age- and sex-matched nondepressed comparators (MS-Depression) included persons with no depression diagnosis, no psychiatric medications, and were asymptomatic on PHQ-2/9. Exposure: Depression diagnosis. Main Outcomes and Measures: We first evaluated if lesions were preferentially located within the depression network compared to other brain regions. Next, we examined if MS+Depression patients had greater lesion burden, and if this was driven by lesions specifically in the depression network. Outcome measures were the burden of lesions (e.g., impacted fascicles) within a network and across the brain. Secondary measures included between-diagnosis lesion burden, stratified by brain network. Linear mixed-effects models were employed. Results: Three hundred-eighty participants met inclusion criteria, (232 MS+Depression: age[SD]=49[12], %females=86; 148 MS-Depression: age[SD]=47[13], %females=79). MS lesions preferentially affected fascicles within versus outside the depression network (ß=0.09, 95% CI=0.08-0.10, P<0.001). MS+Depression had more white matter lesion burden (ß=0.06, 95% CI=0.01-0.10, P=0.015); this was driven by lesions within the depression network (ß=0.02, 95% CI 0.003-0.040, P=0.020). Conclusions and Relevance: We provide new evidence supporting a relationship between white matter lesions and depression in MS. MS lesions disproportionately impacted fascicles in the depression network. MS+Depression had more disease than MS-Depression, which was driven by disease within the depression network. Future studies relating lesion location to personalized depression interventions are warranted.

Minimally invasive distal pancreatectomy for adenocarcinoma of the pancreas.

INTRODUCTION: Minimally invasive (MI) surgery has been widely adopted to treat left-sided pancreatic cancer. However, outcomes are not clearly defined. MATERIALS: Retrospective cohort study utilizing NCDB and NSQIP data. RESULTS: Patients undergoing distal pancreatectomy for pancreatic adenocarcinoma from 2004 to 2016 were included (n = 7347). Utilizing NSQIP (n = 2406), patients were divided into two groups: intention-to-treat (ITT) MI (including MI converted to open, n = 929) and open (n = 1477). Patients undergoing open pancreatectomy were more likely to have longer length of stay (6 vs. 5 days, p=<0.001). On multivariate analysis, open procedures were not associated with mortality (OR 1.24; CI 0.51-3.30, p = 0.64), serious complications (OR 1.03; CI 0.90-1.37, p = 0.79), and any complications (OR 1.07; CI 0.86-1.32, p = 0.56). NCDB patients (n = 4941) were also divided into two groups, ITT MI (n = 1,769, 36%) and open group (n = 3,172, 64%). The median survival was lower in open procedure patients, 23 vs. 27.1 months (p < 0.001). This finding was maintained on multivariable analysis (HR 1.16; CI 1.03-1.32, p = 0.017). CONCLUSION: Based on these data, MI distal pancreatectomy could be considered a standard of care for pancreatic cancer when technically feasible. Although morbidity and mortality were similar, the laparoscopic approach had a shorter length of stay and could hasten recovery.

Improved Overall Survival of Patients with Pancreatic Cancer through Multiagent Chemotherapy and Increased Rates of Surgical Resection.

BACKGROUND: Seminal trials have demonstrated improved survival in pancreatic adenocarcinoma with novel multiagent chemotherapy regimens. To understand the clinical ramifications of this paradigm shift, we reviewed our institutional experience. METHODS: This retrospective cohort study utilized a prospective database at a single institution to study all patients diagnosed with and treated for pancreatic adenocarcinoma between 2000 and 2020. RESULTS: 1,572 patients were included of which 36% were diagnosed before (Era 1) and 64% after (Era 2) 2011. Survival improved in Era 2 (Median survival 10 vs 8 months, HR .79; P < .001). The survival advantage for Era 2 was primarily seen in patients with high-risk disease (12 vs10 months, HR .71; P < .001). A similar trend was noted for patients undergoing surgical resection (26 vs 21 months, HR .80; P = .081) and with imminently resectable tumors (19 vs 15 months, HR .88; P = .4); however, this was not statistically significant. There was no survival advantage for patients with stage IV disease (4 vs 4 months). Patients in Era 2 were more likely to undergo surgery (OR 2.78; CI 2.00-3.92, P < .001). This increase was driven primarily by increased surgical resection for those with high-risk disease (42 vs 20%, OR 3.74; P < .001). DISCUSSION/CONCLUSIONS: This single institutional study showed improved survival after the shift to novel chemotherapy regimens. This was driven by improved survival for patients with high-risk disease and may be due to more effective eradication of microscopic metastatic disease with adjuvant chemotherapy and increased resection rates.

Pathologic Tumor Regression is Associated With Improved Survival in Pancreatic Cancer.

OBJECTIVES: The advent of effective chemotherapy regimens has increased the use of neoadjuvant multiagent chemotherapy in pancreatic cancer. However, the effect of tumor downstaging with neoadjuvant treatment on survival is unclear. METHODS: Retrospective study included all resected patients with pancreatic adenocarcinoma who underwent neoadjuvant chemotherapy with FOLFIRINOX or gemcitabine/Abraxane. Downstaging was quantified using (1) difference between presenting AJCC clinical and final pathologic stage and (2) College of American Pathologists (CAP) Tumor Regression Grading Schema. RESULTS: Eighty-seven patients met inclusion criteria. FOLFIRINOX was the most common regimen, 63.2% vs 21.8%. Change in regimen occurred in 15% of patients. Downstaging based on a difference in AJCC stage group occurred in only 4.6%. In contrast, 45.2% were classified as downstaged by the CAP Tumor Regression of 0-2. Downstaging was similar for FOLFIRINOX gemcitabine/Abraxane (64.7 vs 53.6, P = .12) using the CAP criteria. On univariate analysis, treatment regimen (gemcitabine/Abraxane vs FOLFIRINOX, median survival 27 vs 29 mo; HR 1.57, P = .2) had similar survival. Downstaging by the AJCC stage was not associated with improved survival (HR 1.51, P = .4). However, there was a survival benefit for those downstaged by the CAP Tumor Regression Grading Schema, the median survival of 41 mo vs 25 mo; HR 3.05, P = .009. Improved survival 3.32 (1.35-8.16), P = .009) was maintained on multivariate analysis. CONCLUSION: Survival is significantly improved in those downstaged, as assessed by the CAP Tumor Regression Schema. Downstaging is an important prognostic variable that can help with joint decision making for clinicians and patients.

Preoperative downstaging of pancreatic cancer is associated with improved survival after multi-agent chemotherapy, but not after radiation.

BACKGROUND: Downstaging has been associated with improved survival for many cancers. However, the implications of downstaging are unclear for pancreatic cancer in an era of effective neoadjuvant systemic chemotherapy. METHODS: NCDB retrospective cohort study of resected pancreatic carcinoma treated with neoadjuvant therapy. RESULTS: The study included 73,985 patients: 66,589 with no neoadjuvant therapy, 2,102 neoadjuvant radiation therapy (N-RT), 3,195 neoadjuvant multiagent chemotherapy (N-MAC) and 2.099 with both neoadjuvant radiation and multiagent chemotherapy. There was increased use of N-MAC over the period of this study. Patients selected for treatment with N-MAC had longer survival from surgery on univariate (23.1 vs. 18.7 months, p = < 0.01) and multivariate analyses HR 0.81 (0.76-0.87, p < 0.001) compared to those selected with N-RT. Downstaging was similar in N-RT and N-MAC groups (25.1 vs. 24.1%, p = 0.43). Downstaging following N-MAC was associated with a survival benefit, HR 0.85 (0.74-0.98). However, downstaging following N-RT was not associated with a survival advantage, HR 1.12 (0.99-0.99). CONCLUSION: Clinicians have rapidly adopted N-MAC for treatment of pancreatic cancer. Although the rates of downstaging are similar between treatment groups, response translates into increased survival only with N-MAC and not with N-RT.

Contemporary Treatment Paradigms are Associated with Improved Survival in Pancreatic Cancer.

INTRODUCTION: Over the last decade, a paradigm shift has been made in treating pancreatic cancer. Starting in 2011, several trials demonstrated a survival advantage for multiagent chemotherapy (MAC). However, the implication for survival at the population level remains unclear. METHODS: A retrospective study of the National Cancer Database from 2006 to 2019 was conducted. Patients treated from 2006 to 2010 were classified as "Era 1", and those treated from 2011 to 2019 as "Era 2." RESULTS: A total of 316,393 patients with pancreatic adenocarcinoma were identified, with 87,742 treated in Era 1 and 228,651 in Era 2. Survival increased from Era 1 to Era 2 in all patients and sub-analyses; surgical (18.7 vs 24.6 months, HR .85, 95% CI 0.82-.88, P < .001), imminently resectable (Stage IA and IB, 12.2 vs 14.8 months, HR .90, 95% CI 0.86-.95, P < .001), high-risk (Stage IIA, IIB, and III, 9.6 vs 11.6 months, HR .82, 95% CI 0.79-.85, P < .001), and Stage IV (3.5 vs 3.9 months, HR .86, 95% CI 0.84-.89, P < .001). Survival was decreased for those who were African American (P = .031), on Medicaid (P < .001), or in the lowest quartile of annual income (P < .001). Surgery rates decreased from 20.5% in Era 1 to 19.8% in Era 2 (P < .001). DISCUSSION: Adoption of MAC regimens at a population level correlates with improved pancreatic cancer survival. Unfortunately, socioeconomic factors are associated with an unequal benefit from new treatment regimens, and underuse of surgery for resectable neoplasms persists.

The Effectiveness of Guselkumab by BMI Category Among Patients with Moderate-to-Severe Plaque Psoriasis in the CorEvitas Psoriasis Registry.

INTRODUCTION: Prior studies have demonstrated guselkumab improves disease activity and patient-reported outcomes (PROs) among patients with moderate-to-severe plaque psoriasis. However, the real-world effectiveness of guselkumab across different subgroups [e.g., body mass index (BMI) categories] remains an area of active research. METHODS: This study included patients enrolled in the CorEvitas Psoriasis Registry between July 18, 2017 and March 10, 2020 who had moderate-to-severe psoriasis [Investigator's Global Assessment (IGA) score ≥ 3], initiated guselkumab at a registry visit (index date), and had a follow-up registry visit after persistent guselkumab therapy for 9-12 months. Patients were stratified into three BMI categories: obese (≥ 30 kg/m2), overweight (25- < 30 kg/m2), and underweight/normal weight (< 25 kg/m2). Response rates and mean changes for disease activity outcomes and PROs at follow-up were assessed within each BMI category. RESULTS: Of the 180 patients included in the study, 101 (56%) were obese, 52 (29%) were overweight, and 27 (15%) were underweight/normal weight. Among the obese, overweight, and underweight/normal weight patients, 57%, 58%, and 72%, respectively, achieved an IGA score of 0/1 after 9-12 months of persistent guselkumab treatment. An IGA score of 0 was achieved by 33%, 35%, and 48% of obese, overweight, and underweight/normal weight patients, respectively. A 90% improvement in the Psoriasis Area and Severity Index was achieved by 46%, 46%, and 56% in these respective subgroups. Mean improvements in disease activity and PRO scores were similar among BMI subgroups. CONCLUSION: The results of this real-world study showed improvements in disease severity and several PRO scores within all BMI categories among patients with moderate-to-severe psoriasis treated with guselkumab. These unadjusted findings suggest that obese and overweight patients have comparable absolute improvements to those with lower BMI; however, they may be less likely to achieve relative endpoints. Additional analyses are needed to fully characterize this relationship.

Long-Term Psoriasis Control with Guselkumab, Adalimumab, Secukinumab, or Ixekizumab in the USA.

BACKGROUND: Biologics have revolutionized the management of psoriasis, but response to treatment varies. Loss of treatment efficacy may occur over time, requiring treatment switching or escalation. Claims data on persistence may be informative of real-world treatment outcome. This analysis described persistence and rates of remission of patients with psoriasis initiated on current biologics. METHODS: Adults with psoriasis initiated (index date) on guselkumab, adalimumab, secukinumab, or ixekizumab between 07/13/2017 and 07/31/2020 were identified in the IBM MarketScan Databases. Discontinuation (or end of persistence) was defined as gaps in index biologic supply of more than twice the labelled dosing interval or mode days of supply (> 120 days for guselkumab and > 60 days for adalimumab, secukinumab, and ixekizumab). The proportion of patients reinitiating index therapy post-discontinuation and the proportion achieving remission (proxy definition: no claims for psoriasis-related treatment post-discontinuation among patients with ≥ 6 months of follow-up post-discontinuation) were assessed. RESULTS: There were 3408 patients in the guselkumab (mean age: 47.9 years old; female: 47.1%), 8017 in the adalimumab (47.4 years old; 54.1%), 6123 in the secukinumab (49.4 years old; 54.2%), and 3728 in the ixekizumab cohorts (49.1 years old; 50.3%). The median time to discontinuation was 26.2 months in the guselkumab cohort and 9.9, 12.4, and 12.5 months in adalimumab, secukinumab, and ixekizumab cohorts, respectively. Among those who discontinued index therapy, 22.9% in the guselkumab cohort and 21.1%, 31.9%, and 32.0% in the adalimumab, secukinumab, and ixekizumab cohorts reinitiated it. Remission rates were 17.2% in the guselkumab cohort and 12.4%, 10.5%, and 9.0% in adalimumab, secukinumab, and ixekizumab cohorts, respectively. CONCLUSIONS: Patients on guselkumab showed trends toward better persistence and higher remission rates relative to other biologics. Finding patients who may be in remission suggests potential disease modification with current agents.

Longitudinal temperature measurement can determine humane endpoints in BALB/c mouse models of ESKAPEE infection.

Antimicrobial resistance (AMR) is a worldwide problem, which is driving more preclinical research to find new treatments and countermeasures for drug-resistant bacteria. However, translational models in the preclinical space have remained static for years. To improve animal use ethical considerations, we assessed novel methods to evaluate survival after lethal infection with ESKAPEE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter cloacae, and Escherichia coli) in pulmonary models of infection. Consistent with published lung infection models often used for novel antimicrobial development, BALB/c mice were immunosuppressed with cyclophosphamide and inoculated intranasally with individual ESKAPEE pathogens or sterile saline. Observations were recorded at frequent intervals to determine predictive thresholds for humane endpoint decision-making. Internal temperature was measured via implanted IPTT300 microchips, and external temperature was measured using a non-contact, infrared thermometer. Additionally, clinical scores were evaluated based on animal appearance, behaviour, hydration status, respiration, and body weight. Internal temperature differences between survivors and non-survivors were statistically significant for E. faecium, S. aureus, K. pneumoniae, A. baumannii, E. cloacae, and E. coli, and external temperature differences were statistically significant for S. aureus, K. pneumoniae, E. cloacae, and E. coli. Internal temperature more precisely predicted mortality compared to external temperature, indicating that a threshold of 85ºF (29.4ºC) was 86.0% predictive of mortality and 98.7% predictive of survival. Based on our findings, we recommend future studies involving BALB/c mice ESKAPEE pathogen infection use temperature monitoring as a humane endpoint threshold.

Pancreatic Cancer with Vascular Involvement: Adherence to Current Standard-of-Care Associated with Improved Survival.

METHODS: This study is a retrospective cohort study of National Cancer Data Base (NCDB) data for pancreatic cancer with vascular involvement. RESULTS: A total of 23 903 patients with vascular involvement were included and divided into 3 groups; no treatment (40.6%), medical treatment (36.6%), and resection (22.8%). Of the patients undergoing resection, 31.3% received neoadjuvant multiagent chemotherapy (N-MAC). The remainder were treated with postoperative adjuvant treatment (33.8%), surgery alone (24.9%), preoperative radiotherapy (8.3%), or single-agent preoperative chemotherapy (1.7%). Median survival for N-MAC was superior (28.42 months) when compared to neoadjuvant radiotherapy (20.73 months), neoadjuvant single-agent chemotherapy (20.8 months), postoperative adjuvant therapy (17.87 months), and surgery alone (10.12 months). N-MAC was associated with improved survival compared to postoperative multiagent chemotherapy (P-MAC) (28.4 vs 16.95, HR 1.82; CI 1.64-2.02, P < .0010) (Figure 1). The addition of radiation therapy to N-MAC did not improve survival (27.4 vs 29.8, HR .93; CI .83-1.05, P = .3). Clinical downstaging occurred in 40% of patients treated with N-MAC, and downstaging was associated with improved survival (HR .74; CI .64-.85, P < .001). N-MAC patients were more likely to undergo an R0 resection than P-MAC (74% v. 48, P < .001). CONCLUSIONS: Most resected pancreatic cancer patients in this study with vascular involvement receive either postoperative or no adjuvant therapy. N-MAC increases downstaging, R0 resection rates, and survival.

Revisiting the Pancreatic Fistula Risk Score: Clinical Nomogram Accurately Assesses Risk.

OBJECTIVES: Surgeons have created numerous iterations of the pancreatic fistula risk score (FRS) to predict risk for clinically relevant postoperative pancreatic fistula (CR-POPF). The multitude of often conflicting models makes it difficult for surgeons to apply data in clinical practice. METHODS: We conducted a retrospective cohort study utilizing National Surgical Quality Improvement Program data from 2015 to 2018. The study included patients undergoing pancreaticoduodenectomy. Missing data were resolved with multiple imputations. RESULTS: The study included 5975 patients; 1018 (17%) had a CR-POPF. On multivariate analysis, male sex (odds ratio (OR) 1.60 CI: 1.29-1.98 P < .001), obesity (OR 1.65 CI: 1.31-2.08 P < .001), and soft gland texture (OR 3.21 CI: 2.45-4.23 P < .001) were all associated with increased odds of a CR-POPF. Variables not associated with CR-POPF included diabetes, preoperative bilirubin, preoperative albumin, and American Society of Anesthesiologists (ASA) classification. On multivariate analysis, duct diameter >6 mm (OR .52 CI: .34-.77 P = .001), pancreatic adenocarcinoma pathology (OR .67 CI: .53-.84 P < .001), and neoadjuvant treatment (OR .71 CI: .51-.98 P = .042) were all associated with decreased odds of a CR-POPF. We constructed a clinically relevant nomogram from this model known as the Portland FRS. Model characteristics were superior to previously published FRS models. The area under the curve (AUC) for the Portland FRS was .72 (CI: .704-.737). In comparison, AUCs for the Alternative and Seoul FRS were .70 and .64, respectively. CONCLUSION: Utilizing readily available clinical data, the Portland FRS can accurately predict the risk for pancreatic fistula. The nomogram may assist surgeons in patient counseling and perioperative management.

The Cost of Frailty in Complex Gastrointestinal Surgery.

BACKGROUND: Frailty is a syndrome characterized by decreased physiologic reserve related with aging; it has been associated with increased costs of health care. Factors driving its economic impact remain poorly understood. We examine the association between frailty, complications, and costs in complex gastrointestinal surgery. METHODS: Retrospective review of a prospective database encompassing elective complex gastrointestinal operations from 2017 to 2018 at a tertiary care hospital. Patients were categorized into non-frail (NF): MFI 0, pre-frail (PF): MFI 1-2, and frail (FR): MFI >2 based on the 5-Factor Modified Frailty Index. Linear regression models were applied. RESULTS: 612 patients were included; 268 (44%) were NF, 325 (53%) were PF, and 19 (3%) were FR. The FR group had a longer length of stay (7.26 days) compared to NF (5.05 days) or PF (5.67 days) (p = 0.031). The average total cost of care for all patients was $19,413.06 (CI 18,297.13-20,528.98). The cost for NF was $17,648.54 (CI 15,969.18-19,327.9), PF $20,435.70 (CI 18,911.01-21,960.4, p = .016), and FR patients was $26,809.36 (CI 20,511.9-33,106.81). A complication was observed in 91 patients (14.9%); of these, 76 (12.4%) were serious complications, as defined by NSQIP. There was no difference in incidence of complications (NF 14.93%, PF 14.46%, FR 21.05%, p = .734). On average, a complication added $12,656.67 regardless of frailty category. DISCUSSION: Frail patients are more costly and have a longer length of stay than their more robust counterparts. Complications were the major driver of costs after complex gastrointestinal surgery regardless of frailty status.

Automated analysis of low-field brain MRI in cerebral malaria.

A central challenge of medical imaging studies is to extract biomarkers that characterize disease pathology or outcomes. Modern automated approaches have found tremendous success in high-resolution, high-quality magnetic resonance images. These methods, however, may not translate to low-resolution images acquired on magnetic resonance imaging (MRI) scanners with lower magnetic field strength. In low-resource settings where low-field scanners are more common and there is a shortage of radiologists to manually interpret MRI scans, it is critical to develop automated methods that can augment or replace manual interpretation, while accommodating reduced image quality. We present a fully automated framework for translating radiological diagnostic criteria into image-based biomarkers, inspired by a project in which children with cerebral malaria (CM) were imaged using low-field 0.35 Tesla MRI. We integrate multiatlas label fusion, which leverages high-resolution images from another sample as prior spatial information, with parametric Gaussian hidden Markov models based on image intensities, to create a robust method for determining ventricular cerebrospinal fluid volume. We also propose normalized image intensity and texture measurements to determine the loss of gray-to-white matter tissue differentiation and sulcal effacement. These integrated biomarkers have excellent classification performance for determining severe brain swelling due to CM.