bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pancreatic Enzyme Replacement Therapy for Patients Diagnosed With Pancreaticobiliary Cancer
Authors: Carnie Lindsay E. , Farrell Kelly , Barratt Natalie , Abraham Marc , Gillespie Loraine , Satyadas Thomas , McNamara Mairéad G. , Hubner Richard A. , Geraghty Joe , Bibby Neil , Valle Juan W. , Lamarca Angela 
Published: December 2021

Objective
An algorithm was designed aiming to provide consistency of pancreatic enzyme replacement therapy (PERT) dosing/titration across healthcare professionals in pancreaticobiliary cancers (PBCs). This prospective observational study aimed to validate this algorithm.

Methods
Consecutive patients with inoperable or postoperative PBC with pancreatic exocrine insufficiency (PEI) symptoms, not taking PERT, or taking below the algorithm “starting dose,” were eligible. A dietitian or clinical nurse specialist reviewed patients for up to 3 weeks, titrating PERT as per the algorithm. Feasibility of algorithm deliverability was assessed by the percentage of patients with successful completion (primary objective).

Results
Twenty-five patients were eligible (N = 25): at baseline, 22 took PERT (100% on suboptimal doses, 54.5% taking incorrectly) and 3 initiated PERT because of PEI symptoms. Algorithm completion (20 of 25, 80%) confirming deliverability by dietitians (11 of 12, 92%) and clinical nurse specialists (9 of 13, 69%). Symptom resolution occurred in 8 of 19 (42%), 3 of 7 (43%), and 1 of 3 (33%) patients at first, second, and third reviews, respectively; advice compliance was between 63% and 86%.

Conclusions
This algorithm provides a structured method to titrate PERT. At diagnosis, all patients with PBC should be assessed for PEI and adequate PERT initiated. Regular reviews are required for timely symptom resolution and adequate escalation, facilitating differential diagnosis if refractory symptoms exist.
Survival of Patients With Gastroenteropancreatic Neuroendocrine Tumors and Diabetes Mellitus
Authors: Thapi Sahityasri , Baeg Kiwoon , Kim Michelle K. , Gallagher Emily J. 
Published: December 2021

Objectives
Diabetes mellitus (DM) is associated with an increased risk of gastroenteropancreatic neuroendocrine tumors (GEP-NETs), but the association between DM and GEP-NET survival is unknown. We evaluated disease characteristics and survival in individuals with DM and GEP-NETs.

Methods
Using the Surveillance, Epidemiology, and End Results registry linked to Medicare (SEER-Medicare) claims database, we examined sociodemographics, GEP-NET characteristics, and treatment in patients with and without DM before GEP-NET diagnosis. We compared survival using univariate and multivariate analyses.

Results
We identified 1858 individuals with GEP-NETs: 478 (25.7%) with DM and 1380 (74.3%) without. Significant differences in race (P = 0.002) were found between the DM and non-DM groups. Compared with individuals without DM, those with DM had more gastric (9.7% vs 14.9%), duodenal (6.5% vs 10.0%), and pancreatic (17.0% vs 21.8%), and less jejunal/ileal (18.1% vs 12.8%) NETs (P < 0.0001). Patients with DM had earlier stages (stage I, 37.0%; stage IV, 30.8%) than those without (stage I, 30.6%; stage IV, 36.4%; P = 0.0012). We found no difference in survival (multivariate hazard ratio, 0.97; 95% confidence interval, 0.76–1.23) between groups.

Conclusions
Among patients with and without DM before GEP-NET diagnosis, we found differences in tumor location and stage, but not survival.
Rationale for and Development of the Pancreatic Quantitative Sensory Testing Consortium to Study Pain in Chronic Pancreatitis
Authors: Phillips Anna Evans , Faghih Mahya , Singh Vikesh K. , Olesen Søren Schou , Kuhlmann Louise , Novovic Srdan , Bick Benjamin , Hart Philip A. , Ramsey Mitchell L. , Talukdar Rupjyoti , Garg Pramod K. , Yadav Dhiraj , Drewes Asbjørn Mohr 
Published: December 2021

Objectives
Abdominal pain is the primary symptom of chronic pancreatitis (CP), but pain is difficult to assess, and objective methods for pain assessment are lacking. The characterization of the sensory component of pain as a surrogate for nociception can be achieved by sensory testing using standardized stimuli. Herein, we describe the rationale for and development of an international consortium to better understand and characterize CP pain.

Methods
A collaboration was initially formed between the University of Aalborg, Johns Hopkins University, and the University of Pittsburgh. This group refined the protocol for pancreatic quantitative sensory testing (P-QST) and then expanded the collaboration with plans for incorporating P-QST into prospective studies.

Results
The collaboration has successfully developed a P-QST nomogram. Chronic pancreatitis patients identified with P-QST as having widespread hyperalgesia had higher pain intensity scores, higher prevalence of constant pain, and decreased quality of life. Psychiatric comorbidities were independent of pain phenotypes. Multiple studies are underway to validate these findings and evaluate their utility in clinical trials.

Conclusions
Development of the P-QST Consortium will facilitate collaborative efforts to use P-QST as a means for evaluation and characterization of pain in CP patients, and optimize methods to guide individualized pain management approaches.
Intraoperative Allogeneic Red Blood Cell Transfusion Negatively Influences Prognosis After Radical Surgery for Pancreatic Cancer
Authors: Kanda Taishu , Wakiya Taiichi , Ishido Keinosuke , Kimura Norihisa , Nagase Hayato , Kubota Shunsuke , Fujita Hiroaki , Hagiwara Yusuke , Hakamada Kenichi 
Published: December 2021

Objective
We aimed to investigate the real impact of allogeneic red blood cell transfusion (ABT) on postoperative outcomes in resectable pancreatic ductal adenocarcinoma (PDAC) patients.

Methods
Of 128 patients undergoing resectable PDAC surgery at our facility, 24 (18.8%) received ABT. Recurrence-free survival (RFS) and disease-specific survival (DSS), before and after propensity score matching (PSM), were compared among patients who did and did not receive ABT.

Results
In the entire cohort, ABT was significantly associated with decreased RFS (P = 0.002) and DSS (P = 0.014) before PSM. Cox regression analysis identified ABT (risk ratio, 1.884; 95% confidence interval, 1.015–3.497; P = 0.045) as an independent prognostic factor for RFS. Univariate and multivariate analysis identified preoperative hemoglobin value, preoperative total bilirubin value, and intraoperative blood loss as significant independent risk factors for ABT. Using these 3 variables, PSM analysis created 16 pairs of patients. After PSM, the ABT group had significantly poorer RFS rates than the non-ABT group (median, 9.8 vs 15.8 months, P = 0.022). Similar tendencies were found in DSS rates (median, 19.4 vs 40.0 months, P = 0.071).

Conclusions
This study revealed certain negative effects of intraoperative ABT on postoperative survival outcomes in patients with resectable PDAC.
Noninvasive Models Screen New-Onset Diabetics at Low Risk of Early-Onset Pancreatic Cancer
Authors: Khan Salman , Al Heraki Samee , Kupec Justin T. 
Published: December 2021

Objectives
Several noninvasive models have been developed to identify new-onset diabetics at higher risk of developing pancreatic ductal adenocarcinoma (PDAC). However, they need external validation before implementation.

Methods
This study validated one such model (Boursi model) among a cohort of new-onset diabetics. A bivariate analysis of the model's components was done between patients who developed PDAC and type 2 diabetics. The model performance was assessed through receiver-operative characteristic curve analysis.

Results
Patients with PDAC had significantly lower total cholesterol and alkaline phosphatase at diagnosis of diabetes (P < 0.01). They were observed losing body mass index (BMI) preceding diagnosis (ΔBMI = −0.42 kg/m2, P < 0.01). The model's area under the curve was 0.83 (95% confidence interval, 0.79–0.88). The cutoff that maximized the Youden index was at 0.8%. At this cutoff, the sensitivity was 75%, specificity was 80%, and the prevalence of pancreatic cancer increased from 0.19% at baseline to 0.69%.

Conclusions
Boursi model enriches the prevalence of PDAC among new-onset diabetics.
Estrogen Receptor Expression in Pancreatic Adenocarcinoma
Authors: Lykoudis Panagis M. , Contis John 
Published: December 2021

Abstract
Pancreatic adenocarcinoma remains a chemotherapy-resistant and refractory malignancy with high mortality, unaffected by recent progress in anticancer treatment. Expression of estrogen receptors was detected almost 50 years ago, in both benign and malignant pancreatic cells. However, early preclinical studies in pancreatic cancer led to contradictory findings, and most clinical studies failed to demonstrate an effect with tamoxifen treatment. The identification of a second form of estrogen receptor seems to provide some explanation for these discrepancies. Predominantly expressed in malignant cells and structurally different from what was considered the only estrogen receptor, estrogen receptor β was recognized as a negative prognostic factor and a possible therapeutic target in pancreatic ductal adenocarcinoma. Therefore, findings of research before the identification of estrogen receptor β should be reconsidered, and further studies should be designed to reassess the expression and effect of this specific estrogen receptor type in pancreatic cancer.
Analysis of Outcomes in COVID-19 Patients With Varying Degrees of Hyperlipasemia
Authors: Benias Petros C. , Inamdar Sumant , Wee Diana , Liu Yan , Buscaglia Jonathan M. , Satapathy Sanjaya K. , Trindade Arvind J. 
Published: December 2021

Objectives
Coronavirus disease 2019 (COVID-19) patients may have varying degrees of hyperlipasemia. The aim was to compare outcomes among different levels of hyperlipasemia in patients with COVID-19.

Methods
This is a retrospective study examining outcomes among hospitalized COVID-19 patients with a lipase <3× upper limit of normal (ULN), asymptomatic hyperlipasemia (>3× ULN), secondary pancreatitis (typical respiratory COVID-19 symptoms and found to have pancreatitis), and primary pancreatitis (presenting with pancreatitis).

Results
Of 11,883 patients admitted with COVID-19, 1560 patients were included: 1155 patients had normal serum lipase (control group), 270 had elevated lipase <3× ULN, 46 patients had asymptomatic hyperlipasemia with lipase >3× ULN, 57 patients had secondary pancreatitis, and 32 patients had primary pancreatitis. On adjusted multivariate analysis, the elevated lipase <3× ULN and asymptomatic hyperlipasemia groups had worse outcomes with higher mortality (odds ratio [OR], 1.6 [95% confidence interval [CI], 1.2–2.2) and 1.1 [95% CI, 0.5–2.3], respectively), higher need for mechanical ventilation (OR, 2.8 [95% CI, 1.2–2.1] and 2.8 [95% CI, 1.5–5.2], respectively), and longer length of stay (OR, 1.5 [95% CI, 1.1–2.0] and 3.16 [95% CI, 1.5–6.5], respectively).

Conclusions
Patients with COVID-19 with elevated lipase <3× ULN and asymptomatic hyperlipasemia have generally worse outcomes than those with pancreatitis.
Anti‐Proteinase 3 Antibodies as a Biomarker for Ulcerative Colitis and Primary Sclerosing Cholangitis in Children
Authors: Laass Martin Walter , Ziesmann Josefine , de Laffolie Jan , Röber Nadja , Conrad Karsten 
Published: December 2021

ABSTRACTObjectives:Anti‐neutrophil cytoplasmic antibody (ANCA) directed against proteinase 3 (PR3) is a marker for granulomatosis with polyangiitis, but is also found in patients with inflammatory bowel disease (IBD), mainly ulcerative colitis (UC). The aim of our study was to investigate ANCA and PR3‐ANCA in paediatric IBD.Methods:We tested 326 paediatric IBD patients and 164 controls for anti‐Saccharomyces cerevisiae antibodies (ASCA), ANCA (indirect immunofluorescence, IIF) and PR3‐ANCA (chemiluminescence immunoassay). We applied the Paris classification for paediatric IBD and documented liver manifestations such as primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH).Results:We found PR3‐ANCA in 49/121 (40%) of UC, 20/187 (11%) of Crohn disease (CD) and 2/18 (11%) of IBD‐unclassified (IBD‐U) patients but in none of the controls. 54% UC and 12% CD patients were positive for ANCA (IIF). PR3‐ANCA positive UC patients were characterised by more extensive disease (P = .070). Fourteen of 21 (67%) of UC patients with backwash ileitis were anti‐PR3 ANCA‐positive (P = .011). We diagnosed PSC or PSC/AIH in 19 UC and 3 IBD‐U patients. Fifteen of 22 (68%) patients with PSC or PSC/AIH were anti‐PR3‐ANCA positive in contrast to 36 of 117 (32%) patients without PSC (P = .001). PR3‐ANCA positive patients showed higher levels of gamma‐glutamyl transferase, alanine transaminase and aspartate transferase (P < 0.001, 0.001, 0.006, respectively). Forty‐seven percent of CD and 6% of UC patients were ASCA‐IgA positive. PR3‐ANCA‐positive and ‐negative patients showed no significant differences concerning age at diagnosis, disease activity, need for drugs, and number of hospitalisations.Conclusions:Our study provides data for PR3‐ANCA as a potential serological marker for paediatric UC and PSC.
Do intra-articular knee injuries detected by preoperative MRI affect the clinical management of extensor mechanism ruptures?
Authors: Turner Elizabeth H.G. , Akoh Craig C. , Hetzel Scott J. , Markhardt B. Keegan , Spiker Andrea M. 
Published: December 2021

Abstract

Objectives:
We sought to determine the prevalence of intra-articular findings at the time of extensor mechanism injury that required subsequent surgical intervention.

Design:
Retrospective cohort study.

Setting:
Level 1 academic trauma center.

Patients/participants:
Sixty-seven knees in 66 nonconsecutive patients (mean age 53.6 years, 95.6% male) with extensor mechanism injury and preoperative magnetic resonance imaging (MRI) before undergoing open primary surgical repair.

Main outcome measurements:
Patellar or quadriceps tendon rupture, high or low injury energy level, and age above or below 45 years were used to stratify patients. The primary outcome was additional surgery for intra-articular injury. Demographics, comorbidities, mechanism and location of injury, and internal derangements based on MRI findings were also collected.

Results:
Fifty-one knees (76.1%) had quadriceps tendon injury, 13 knees (19.4%) had patellar tendon injury, and 3 knees (4.6%) had both. Thirty-four knees (50.7%) had intra-articular pathology and 3 (4.5%) required additional surgery, including 1 knee (7.7%) with patellar tendon injury and 2 knees (3.9%) with quadriceps tendon injury. Patellar tendon injuries were more commonly associated with cruciate ligament injury (P < .01) and occurred in younger patients (P < .001) than quadriceps tendon injury.

Conclusions:
50.7% of cases with extensor mechanism injury had intra-articular pathology but only 4.5% required additional surgery. The results of our study suggest that preoperative MRI is unlikely to be of significant clinical utility in most extensor mechanism injuries but should be considered in cases of patellar tendon rupture in younger patients where the incidence of concomitant cruciate ligament injury is higher.

Level of evidence:
Diagnostic Level III.
Circulating CD4+ TEMRA and CD4+ CD28− T cells and incident diabetes among persons with and without HIV
Authors: Bailin Samuel S. , Kundu Suman , Wellons Melissa , Freiberg Matthew S. , Doyle Margaret F. , Tracy Russell P. , Justice Amy C. , Wanjalla Celestine N. , Landay Alan L. , So-Armah Kaku , Mallal Simon , Kropski Jonathan A. , Koethe John R. 
Published: December 2021

Objective:
A higher proportion of circulating memory CD4+ T cells is associated with prevalent diabetes mellitus in persons with HIV (PWH) and HIV-negative persons. We assessed whether circulating T-cell subsets could also identify individuals who will subsequently develop diabetes.

Design:
This is a longitudinal follow-up study of PWH and similar HIV-negative individuals from the Veterans Aging Cohort Study who provided peripheral mononuclear blood cells between 2005 and 2007.

Methods:
We quantified T-cell subsets using flow cytometry and functional assays to identify CD4+ and CD8+ naive, activated, senescent, memory (central, effector, and effector RA+), and TH1, TH2, and TH17-phenotype cells. The occurrence of an incident diabetes diagnosis (i.e. after baseline blood draw) was adjudicated by a two-physician chart review. Cox proportional hazards models adjusted for traditional risk factors, cytomegalovirus serostatus, and plasma inflammatory biomarkers assessed the relationship between T-cell subsets and incident diabetes.

Results:
One thousand, eight hundred and thirty-seven participants (1259 PWH) without diabetes at baseline were included; 69% were black, 95% were men, and median follow-up was 8.6 years. Higher baseline frequencies of CD4+ T effector memory RA+ (TEMRA) cells defined as CD45RA+ CD27− (P = 0.04) and senescent T cells defined as CD4+ CD28− (P = 0.04) were associated with incident diabetes in PWH only.

Conclusions:
Higher frequencies of CD4+ TEMRA and CD4+ CD28− T cells were associated with incident diabetes in PWH only after adjustment for other factors. Additional studies are necessary to assess whether these cells act in blood via inflammatory mediators or reflect T-cell populations in metabolically active tissues.
Contributions of chronic tobacco smoking to HIV-associated brain atrophy and cognitive deficits
Authors: Liang Hua-Jun , Ernst Thomas , Cunningham Eric , Chang Linda 
Published: December 2021

Objectives:
Tobacco smoking is linked to cognitive deficits and greater white matter (WM) abnormalities in people with HIV disease (PWH). Whether tobacco smoking additionally contributes to brain atrophy in PWH is unknown and was evaluated in this study.

Design:
We used a 2 × 2 design that included 83 PWH (43 nonsmokers, 40 smokers) and 171 HIV-seronegative (SN, 106 nonsmokers, 65 smokers) participants and assessed their brain structure and cognitive function.

Methods:
Selected subcortical volumes, voxel-wise cortical volumes and thickness, and total WM volume were analyzed using FreeSurfer. Independent and interactive effects of HIV and smoking were evaluated with two-way analysis of covariance on cognitive domain Z-scores and morphometric measures on T1-weighted MRI.

Results:
Regardless of smoking status, relative to SN, PWH had smaller brain volumes [basal ganglia, thalami, hippocampi, subcortical gray matter (GM) and cerebral WM volumes (P = 0.002–0.042)], steeper age-related declines in the right superior-parietal (interaction: P < 0.001) volumes, and poorer attention/working memory and learning (P = 0.016–0.027). Regardless of HIV serostatus, smokers tended to have smaller hippocampi than nonsmokers (−0.6%, P = 0.055). PWH smokers had the smallest total and regional subcortical GM and cortical WM volume and poorest cognitive performance.

Conclusions:
Tobacco smoking additionally contributed to brain atrophy and cognitive deficits in PWH. The greater brain atrophy in PWH smokers may be due to greater neuronal damage or myelin loss in various brain regions, leading to their poor cognitive performance. Therefore, tobacco smoking may exacerbate or increase the risk for HIV-associated neurocognitive disorders.
Clinical Characteristics for Predicting Recovery of Acquired Fourth Cranial Nerve Palsy
Authors: Kim Jae Hyun , Choi Hee-Young , Jeon Hyeshin 
Published: December 2021

Background:Fourth cranial nerve palsy is the most common disease diagnosed in patients with vertical diplopia. Although it is reported to present a good prognosis, there are currently no agreed on prognostic factors that anticipate the recovery of the palsy other than the etiology. The purpose of this study was to investigate the prognostic factors of acquired fourth cranial nerve palsy.Methods:The medical records of consecutive patients diagnosed with acquired unilateral fourth cranial nerve palsy from 2010 to 2020 and followed up for ≥6 months were retrospectively reviewed. The cause and degree of palsy, ocular deviation (horizontal, vertical, and cyclo), and fundus torsion were reviewed. The cause of palsy was classified as ischemic, traumatic, intracranial mass, others, or idiopathic. Patients were divided into 2 groups according to palsy recovery: complete recovery (group CR) or not CR (group NCR). The clinical characteristics of the 2 groups were compared, and the risk factors for incomplete recovery were investigated.Results:Thirty-five patients (25 men) were included in the study. The average age was 55.94 ± 16.11 years. CR was achieved in 23 patients (65.7%), and the time to recovery was 3.91 ± 4.03 months. The most common cause was traumatic (40.0%), followed by ischemia (37.1%), intracranial mass (11.4%), others (8.6%), and idiopathic (2.9%). The degree of palsy and fundus torsion was significantly higher in group NCR (P= 0.010 andP= 0.001). Severe oculomotor limitation, large fundus torsion, and intracranial mass cause rather than ischemic cause indicated a higher risk of incomplete or no recovery (P= 0.016,P= 0.009, andP= 0.043).Conclusion:Identifying whether a patient has an intracranial mass, severe oculomotor limitation, or large fundus excyclotorsion may be useful for predicting the recovery of acquired unilateral fourth cranial nerve palsy.
Online prescribing for sexually transmitted infections – what’s on offer? An evaluation of internet pharmacies based in the United Kingdom
Authors: Okecha Elizabeth , Boardman Emily , Patel Saleha , Morgan Emile 
Published: December 2021

AbstractBackgroundOnline pharmacies offer an alternative approach for patients to manage their sexual health. Our aim was to determine the type of antimicrobials sold as treatment for sexually transmitted infections (STIs) by UK internet pharmacies and if providers were adhering to national guidelines.MethodsA search engine results page (SERP) generated a list of registered UK online pharmacies offering treatment for the following infections: Chlamydia trachomatis, Neisseria gonorrhoeae, Herpes simplex and Trichomonas vaginalis. An initial audit in 2017 benchmarked each provider against the British Association of Sexual Health & HIV (BASHH guidelines. Results were fed back to each provider before re-audit in 2020. Websites selling antibiotics for non-gonococcal urethritis (NGU) and Mycoplasma genitalium were included at re-audit.ResultsThere were 30 pharmacies identified in 2017 of which, five were excluded. Treatment could be obtained for Neisseria gonorrhoeae from five pharmacies without providing a culture result; three (60%) pharmacies sold BASHH approved antibiotics for Neisseria gonorrhoeae. All 25 pharmacies sold Chlamydia trachomatis treatment; 22 (88%) offered first line treatment options but no website assessed for proctitis. Herpes simplex treatment was sold on 22 websites of which, 13 (59%) offered treatment recommended by BASHH. Trichomonas vaginalis treatment was sold by four websites in line with BASHH. Results at re-audit showed an improvement in standards, although advice before, during and after treatment remained variable.DiscussionOur work has allowed us to engage with providers to improve prescribing within the UK online pharmacy industry. However, tougher regulation is needed in order to embed sustainable change for patients who choose to access treatment online.