bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhanced Recovery Pathway Benefits Patients Undergoing Nonelective Colorectal Surgery
Authors: Liska David , Novello Matteo , Cengiz Bora Turgut , Holubar Stefan D. , Aiello Alexandra , Gorgun Emre , Steele Scott R. , Delaney Conor P. 
Published: October 2019

Objective:
The aim of our study was to determine if an enhanced recovery pathway (ERP) can successfully be applied in nonelective colorectal surgery.

Background:
ERPs have been shown to reduce hospital length of stay (LOS), complications, and costs after elective colorectal surgery. Yet, little data exist regarding the benefits of ERPs in patients undergoing nonelective colorectal surgery. We hypothesized that ERP implementation in a nonelective colorectal surgery population is associated with decreased postoperative LOS.

Methods:
A prospectively-maintained database was used to identify consecutive patients undergoing colorectal surgery after emergency room (ER) or hospital transfer admissions over a period from 2 years before until 1 year after implementation of a comprehensive ERP. The primary endpoint was LOS. Secondary endpoints included total LOS [TLOS = postoperative LOS + LOS of readmission(s)], readmission rates, complication rates, 30-day mortality, and hospital costs. Univariate and multivariate analyses were performed to assess the relationship between ERP implementation and LOS.

Results:
We identified 269 pre-ERP and 135 ERP patients fulfilling the inclusion criteria. Admit source (ER 43.4% vs transfers 56.7%), Charlson comorbidity index, American Society of Anesthesiologists (ASA) status, diagnosis (inflammatory bowel disease 45.8%, malignancy 19.6%, benign intestinal obstructions 10.4%, diverticulitis 9.4%, others 10.4%), and blood loss were comparable (P > 0.05) between the cohorts. Pre-ERP patients had a higher number of previous abdominal surgeries, whereas post-ERP patients had more laparoscopy and more compliance with ERP elements. ERP patients had a shorter postoperative LOS [6 (4, 10) vs 7 (5, 12) days; P = 0.0007]. Hospital costs were 13.4% lower (P = 0.004). Postoperative 30-day morbidity, mortality, and readmissions were comparable, although reoperation rate was higher in the ERP group. On multivariate analysis, ERP implementation and laparoscopy were the only modifiable variables independently associated with shorter LOS, whereas longer operative times and higher ASA classification were associated with longer LOS.

Conclusions:
Patients undergoing nonelective colorectal surgery after ER or hospital transfer admission benefit from the use of an ERP, demonstrating decreased LOS and costs without an increase in complications.
Comparing Outcomes and Costs of Surgical Patients Treated at Major Teaching and Nonteaching Hospitals
Authors: Silber Jeffrey H. , Rosenbaum Paul R. , Niknam Bijan A. , Ross Richard N. , Reiter Joseph G. , Hill Alexander S. , Hochman Lauren L. , Brown Sydney E. , Arriaga Alexander F. , Kelz Rachel R. , Fleisher Lee A. 
Published: October 2019

Objective:To compare outcomes and costs between major teaching and nonteaching hospitals on a national scale by closely matching on patient procedures and characteristics.Background:Teaching hospitals have been shown to often have better quality than nonteaching hospitals, but cost and value associated with teaching hospitals remains unclear.Methods:A study of Medicare patients at 340 teaching hospitals (resident-to-bed ratios ≥ 0.25) and matched patient controls from 2444 nonteaching hospitals (resident-to-bed ratios < 0.05).We studied 86,751 pairs admitted for general surgery (GS), 214,302 pairs of patients admitted for orthopedic surgery, and 52,025 pairs of patients admitted for vascular surgery.Results:In GS, mortality was 4.62% in teaching hospitals versus 5.57%, (a difference of −0.95%, <0.0001), and overall paired cost difference = $915 (P< 0.0001). For the GS quintile of pairs with highest risk on admission, mortality differences were larger (15.94% versus 18.18%, difference = −2.24%,P< 0.0001), and paired cost difference = $3773 (P< 0.0001), yielding $1682 per 1% mortality improvement at 30 days. Patterns for vascular surgery outcomes resembled general surgery; however, orthopedics outcomes did not show significant differences in mortality across teaching and nonteaching environments, though costs were higher at teaching hospitals.Conclusions:Among Medicare patients, as admission risk of mortality increased, the absolute mortality benefit of treatment at teaching hospitals also increased, though accompanied by marginally higher cost. Major teaching hospitals appear to return good value for the extra resources used in general surgery, and to some extent vascular surgery, but this was not apparent in orthopedic surgery.
International Validation of Reduced Major Morbidity After Minimally Invasive Distal Pancreatectomy Compared With Open Pancreatectomy
Authors: Klompmaker Sjors , de Rooij Thijs , Koerkamp Bas Groot , Shankar Anuraj H. , Siebert Uwe , Besselink Marc G. , Moser A. James 
Published: October 2019

Objective:
To quantify the nationwide impact of minimally invasive distal pancreatectomy (MIDP) on major morbidity as compared with open distal pancreatectomy (ODP).

Background:
A recent randomized controlled trial (RCT) demonstrated significant reduction in time to functional recovery after MIDP compared with ODP, but was not powered to assess potential risk reductions in major morbidity.

Methods:
International cohort study using the American College of Surgeons’ National Quality Improvement Program (ACS-NSQIP) (88 centers; 2014–2016) to evaluate the association between surgical approach (MIDP vs ODP) and 30-day composite major morbidity (CMM; death or severe complications) with external model validation using Dutch Pancreatic Cancer Group data (17 centers; 2005–2016). Multivariable logistic regression assessed the impact of nationwide MIDP rates between 0% and 100% on postoperative CMM at conversion rates between 0% and 25%, using estimated marginal effects. A sensitivity analysis tested the impact at various scenarios and patient populations.

Results:
Of 2921 ACS-NSQIP patients, 1562 (53%) underwent MIDP with 18% conversion, and 1359 (47%) underwent ODP. MIDP was independently associated with reduced CMM [odds ratio (OR) 0.50, 95% confidence interval (CI) 0.42–0.60, P < 0.001], confirmed by external model validation (n = 637, P < 0.003). The association between rising MIDP implementation rates and falling postoperative morbidity was linear between 0% (all ODP) and 100% (all MIDP). The absolute risk reduction for CMM was 11% (95% CI 7.3%–15%) at observed conversion rates and improved to 14% (95% CI 11%–18%) as conversion approached 0%. Similar effects were seen across subgroups.

Conclusion:
This international study predicted a nationwide 11% risk reduction for CMM after MIDP versus ODP, which is likely to improve as conversion rates decrease. These findings confirm secondary outcomes of the recent LEOPARD RCT.
Oncological Impact of High Vascular Tie After Surgery for Rectal Cancer
Authors: Boström Petrus , Hultberg Daniel Kverneng , Häggström Jenny , Haapamäki Markku M. , Matthiessen Peter , Rutegård Jörgen , Rutegård Martin 
Published: October 2019

Objective:
The purpose of this study was to investigate the impact of tie level on oncological outcomes in rectal cancer surgery.

Summary background data:
Theoretically, a high tie of the inferior mesenteric artery could facilitate removal of apical node metastases and improve tumor staging accuracy. However, no appropriately sized randomized controlled trial exists and results from observational studies are not consistent.

Methods:
All stage I–III rectal cancer patients who underwent abdominal surgery with curative intention in 2007 to 2014 were identified and followed, using the Swedish Colorectal Cancer Registry. Primary outcome was cancer-specific survival, whereas overall and relative survival, locoregional and distant recurrence, and lymph node harvest were secondary outcomes, with high tie as exposure. We used propensity score matching to emulate a randomized controlled trial, and then performed Cox regression analyses to estimate hazard ratios (HRs) with confidence intervals (CIs).

Results:
Some 8287 patients remained for analysis, of which 37% had high tie surgery. After propensity score matching, the 5-year cancer-specific survival rate was overall 86% and we found no association between the level of tie and cancer-specific (HR 0.92, 95% CI 0.79–1.07) or overall (HR 0.98, 95% CI 0.89–1.08) survival, nor to locoregional (HR 0.85, 95% CI 0.59–1.23) or distant (HR 1.01, 95% CI 0.88–1.15) recurrence, nor to relative survival (HR 1.05, 95% CI 0.85–1.28). Stratification and sensitivity analyses were similarly insignificant, after adjustment for confounding. Total lymph node harvest was, however, increased after high tie surgery (P < 0.01), but no differences were seen regarding positive nodes (P = 0.72).

Conclusion:
In this nationwide cohort study, the level of tie did not influence any patient-oriented oncological outcome, neither overall nor in node-positive patients. This would allow the patient's anatomical configuration and the surgeon's preferences to determine the level of tie.
The Impact of Age and Luminal Preservation on the Development of Intestinal Preservation Injury in Rats
Authors: Søfteland John Mackay , Casselbrant Anna , Akyürek Levent M. , Hellström Mats , Oltean Mihai 
Published: October 2019

Background.
Organs from older donors are believed to withstand ischemia worse than those from younger donors. The effect of age on the development of intestinal preservation injury (IPI) is unclear.

Methods.
We compared the development of IPI in intestines from young (3 mo), adult (14 mo), and old (20 mo) rat donors and assessed if luminal preservation (LP) is effective in delaying IPI. Small intestines were perfused with, and stored in, preservation solution (Custodiol) with or without LP solution (polyethylene glycol 3350). IPI was studied using histology (Chiu score, Alcian blue staining), Western blot, and electrophysiological assessment (Ussing chamber) at 4, 8, and 14 hours.

Results.
Intestines of old rats did not show major histological alterations, whereas their aortas and kidneys revealed typical age-related changes (arteriosclerosis and glomerulosclerosis). Intestines from old rats fared similarly to their younger counterparts at all time points regarding preservation injury and goblet cells count. Intestines undergoing LP showed fewer histological signs of damage and higher goblet cells count when compared with samples without LP, regardless of donor age. Ussing chamber experiments indicated a time-dependent deterioration of all parameters studied, which was delayed by the use of LP.

Conclusions.
Older intestines did not convincingly demonstrate a faster IPI compared with intestines from adult and young donors. The small differences between the age groups were nullified by the use of LP. LP significantly delayed the IPI in all age groups and may allow for longer preservation periods without an increased risk of mucosal damage.
Inducing Transient Mixed Chimerism for Allograft Survival Without Maintenance Immunosuppression With Combined Kidney and Bone Marrow Transplantation: Protocol Optimization
Authors: Lee Kyo Won , Park Jae Berm , Park Hyojun , Kwon Yeongbeen , Lee Ji Soo , Kim Kyeong Sik , Chung Young Jae , Rhu Jin Soo , Choi Sooin , Kwon Ghee Young , Kim Hee Jin , Kang Eun-Suk , Jung Chul Won , Shin Eui-Cheol , Kawai Tatsuo , Kim Sung Joo , Joh Jae-Won 
Published: October 2019

Background.
Tolerance induction is an important goal in the field of organ transplantation. We have sequentially modified our conditioning regimen for induction of donor-specific tolerance in recipients of major histocompatibility complex-mismatched combined kidney and bone marrow transplantation (CKBMT).

Methods.
From December 2011 to May 2017, 8 major histocompatibility complex-mismatched patients received CKBMT. The initial conditioning regimen (protocol 1) consisted of cyclophosphamide (CP), rituximab, rabbit antithymocyte globulin, and thymic irradiation. Tacrolimus and steroids were used for the maintenance of immunosuppression (IS).

Results.
This regimen was complicated by transient acute kidney injury, which has been the major clinical feature of engraftment syndrome and side effects of CP, although one of 2 subjects successfully discontinued his IS for 14 months. The conditioning regimen was modified by reducing the CP dose and adding fludarabine (protocol 2). The final modification was reducing the fludarabine and rabbit antithymocyte globulin doses (protocol 3). Mixed chimerism, detected by the short tandem repeat method, was achieved transiently in all subjects for 3–20 weeks. Among the 3 subjects treated with protocol 2, IS was successfully discontinued for >35 months in one subject, but the other 2 subjects suffered from severe BK virus-associated nephritis. All 3 subjects treated with protocol 3 tolerated the protocol well and have successfully discontinued IS for >4–41 months. Interestingly, de novo donor-specific antibody was not detected in any subject during all the follow-up periods.

Conclusions.
Our clinical trial has shown that long-term renal allograft survival without maintenance IS can be achieved by induction of mixed chimerism following CKBMT.
Clinicopathologic Assessment of Monoclonal Immunoglobulin-associated Renal Disease in the Kidney Allograft: A Retrospective Study and Review of the Literature
Authors: Kamal Jeanne , Khairallah Pascale , Crew Russell J. , Ye Xiaoyi , Swanson Sidney J. , Kudose Satoru , Park David C. , Appel Gerald B. , Markowitz Glen S. , D’Agati Vivette D. , Batal Ibrahim 
Published: October 2019

Background.
Monoclonal immunoglobulin (MIg)-associated renal disease (MIgARD) comprises a group of disorders caused by direct deposition of paraproteins in the kidney. Allograft MIgARD is infrequently encountered and poorly characterized.

Methods.
First, we assessed our allograft biopsies diagnosed with MIgARD between 2007 and 2018. The cohort included the following 26 patients: proliferative glomerulonephritis with MIg deposits (PGNMID) (n = 13), AL amyloidosis (n = 5), light chain deposition disease (n = 5), light chain proximal tubulopathy (n = 2), and light chain cast nephropathy (n = 1). Second, we conducted a literature review to evaluate the rare non-PGNMID entities. We identified 20 studies describing 29 patients that were added to our cohort (total n = 42).

Results.
Part 1: Patients’ median age was 55 years; 31% were women, and 19% were blacks. Twelve patients (46%) lost their grafts at a median of 8 months after diagnosis. Compared to non-PGNMID, PGNMID patients had lower frequency of detectable paraproteins (31% versus 92%, P = 0.004) and hematologic neoplasms (23% versus 77%, P = 0.02). Within PGNMID group, 6 patients changed their apparent immunofluorescence phenotype between monotypic and polytypic, while all 3 patients with hematologic neoplasms had substructure on electron microscopy. Part 2: Whereas light chain cast nephropathy occurred the earliest and had the worst graft survival, AL amyloidosis occurred the latest and had the best graft survival.

Conclusions.
MIgARD in the kidney allograft is associated with poor prognosis. While posttransplant PGNMID can change its apparent clonality by immunofluorescence supporting oligoclonal immune responses, the presence of deposit substructure is an important indicator of underlying hematologic neoplasm. Non-PGNMID are often associated with hematologic neoplasms and varied prognosis.
TNFAIP8 Deficiency Exacerbates Acute Graft Versus Host Disease in a Murine Model of Allogeneic Hematopoietic Cell Transplantation
Authors: Kumari Reena , Palaniyandi Senthilnathan , Strattan Ethan , Huang Timothy , Kohler Katharina , Jabbour Nashwan , Dalland Joanna , Du Jing , Kesler Melissa V. , Chen Youhai H. , Hildebrandt Gerhard C. 
Published: October 2019

Background.
Gastrointestinal acute graft-versus-host disease (GVHD) occurring after allogeneic hematopoietic cell transplant is an allo-reactive T cell and inflammatory cytokine driven organ injury with epithelial apoptosis as 1 of its hallmark findings and is associated with significant mortality. Tumor necrosis factor (TNF)-alpha-induced protein 8 (TNFAIP8 or TIPE) acts as a negative mediator of apoptosis via inhibition of caspase-3 activation, promotes cell proliferation and Tipe
−/− deficiency is associated with increased inflammation.

Methods.
To evaluate the role of TIPE in acute GVHD, naive C57BL/6 and Tipe
−/− C57BL/6 mice were conditioned with 1000 cGy single dose total body irradiation, followed by transplantation of 10 million bone marrow cells and 20 million splenocytes from either syngeneic C57BL/6 or allogeneic BALB/c donors.

Results.
Allo TIPE-deficient mice developed exacerbated gut GVHD compared with allo controls and had significantly decreased survival (6 wk overall survival: 85% versus 37%; P < 0.05), higher clinical GVHD scores, more profound weight loss, increased serum proinflammatory cytokines (interleukin-17A, TNF, interleukin-6, and interferon-γ). T-cell infiltration into the ileum was increased; epithelial proliferation was decreased along with significantly higher levels of chemokines KC and monokine induced by gamma interferon. Using bone marrow chimeric experiments, TIPE was found to have a role in both hematopoietic and nonhematopoietic cells.

Conclusions.
Absence of TIPE results in excessive inflammation and tissue injury after allo-HCT, supporting that TIPE confers immune homeostasis and has tissue-protective function during the development of gut GVHD and may be a potential future target to prevent or treat this complication after allogeneic HCT.
A Laboratory Method for Determining Bacterially Formed Odorants and Reducing Odor in Absorbent Incontinence Products
Authors: Ryttsén Frida , Lafqvist Sofia , Wall Torun , Forsgren-Brusk Ulla , Larsson Peter 
Published: October 2019

PURPOSE:
The purpose of this study was to design a laboratory test method to mimic the formation of bacterially formed odorants during the use of absorbent urinary incontinence products. Three odor inhibitors with different modes of action were tested and evaluated.

METHODS:
Bacterially formed odorants in incontinence products were evaluated by adding a synthetic urine inoculated with a mixture of 4 bacterial strains to product samples cut from the incontinence products. The product samples were incubated in sealed flasks. The odorants that formed in the head space were sampled onto adsorbent tubes and analyzed by gas chromatography. The inhibitory effects of low pH, ethylenediaminetetraacetic acid (EDTA), and activated carbon were then measured.

RESULTS:
This technique enabled production of known odorants 3-methylbutanal, guaiacol, diacetyl, and dimethyl disulfide (DMDS) in concentrations of 50 to 600 ng/L in incontinence products. The method was further evaluated by testing 3 types of odor inhibitors; EDTA significantly reduced formation of all 4 odorants (P < .001). Lowering the pH from 6.0 to 4.9 decreased levels of 3-methylbutanal, DMDS, and guaiacol (P < .001); however, diacetyl levels increased (P < .001). Activated carbon significantly reduced the formation of diacetyl, DMDS, guaiacol, and 3-methylbutanal (P < .001).

CONCLUSIONS:
The technique we developed can be used to evaluate inhibitors with different modes of action to determine odor control in incontinence products. The odorants formed are produced by bacteria and have been identified as key contributors to the odor of used incontinence products. This work can be a step toward establishing a standard in the field of incontinence and odor control; creation of a standard will help the health care sector compare products to be purchased and benefit patients through the development of better products.
Modification of the association between paroxetine serum concentration and SERT-occupancy by ABCB1 (P-glycoprotein) polymorphisms in major depressive disorder
Authors: Simoons Mirjam , Mulder Hans , Appeldoorn Jerôme T.Y. , Risselada Arne J. , Schene Aart H. , van Schaik Ron H.N. , van Roon Eric N. , Ruhé Eric G. 
Published: October 2019

Background
Selective serotonin reuptake inhibitors (SSRIs) exert substantial variability in effectiveness in patients with major depressive disorder (MDD), with up to 50–60% not achieving adequate response. Elucidating pharmacokinetic factors that explain this variability is important to increase treatment effectiveness.

Objectives
To examine potential modification of the relationship between paroxetine serum concentration (PSC) and serotonin transporter (SERT)-occupancy by single nucleotide polymorphisms (SNPs) of the ABCB1 gene, coding for the P-glycoprotein (P-gp) pump, in MDD patients. To investigate the relationship between ABCB1 SNPs and clinical response.

Methods
Patients had MDD and received paroxetine 20 mg/day. We measured PSC after 6 weeks. We quantified SERT-occupancy with SPECT imaging (n = 38) and measured 17-item Hamilton Depression Rating Scale (HDRS17)-scores at baseline and after 6 weeks (n = 81). We genotyped ABCB1 at rs1045642 [3435C>T], rs1128503 [1236C>T], rs2032582 [2677G>T/A] and rs2235040 [2505G>A]. For our primary aim, we modeled mean SERT-occupancy in an E
max nonlinear regression model with PSC and assessed whether the model improved by genetic subgrouping. For our secondary aim, we used multivariate linear regression analysis.

Results
The rs1128503 and rs2032582 SNPs modified the relationship between PSC and SERT-occupancy in both our intention-to-treat and sensitivity analyses at the carriership level. However, we could not detect significant differences in clinical response between any of the genetic subgroups.

Conclusion
Pharmacokinetic influences of the ABCB1 rs1128503 and rs2032582 represent a potentially relevant pharmacogenetic mechanism to consider when evaluating paroxetine efficacy. Future studies are needed to support the role of ABCB1 genotyping for individualizing SSRI pharmacotherapy.
Predicting the required pre-surgery blood volume in surgical patients based on machine learning
Authors: Li Ruilin , Han Xinyin , Sun Liping , Feng Yannan , Sun Xiaolin , He Xiaoyu , Zhang Yu , Zhu Haidong , Zhao Dan , Dai Chuangchuang , He Zhipeng , Chen Shanyu , Wang Xin , Li Weizhong , Chi Xuebin , Yu Yang , Niu Beifang , Wang Deqing 
Published: October 2019

AbstractPrecisely predicting the required pre-surgery blood volume (PBV) in surgical patients is a formidable challenge in China. Inaccurate estimation is associate with excessive costs, postponed surgeries and adverse outcome after surgery due to in sufficient supply or inventory. This study aimed to predict required PBV based on machine learning techniques. 181,027 medical documents over 6 years were cleaned and finally obtained 92,057 blood transfusion records. The blood transfusion and surgery related factors of perioperative patients, surgeons experience volumes and the actual volumes of transfused RBCs were extracted. 6 machine learning algorithms were used to build prediction models. The surgery patients received allogenic RBCs or without transfusion, had total volume less than 10 units, or had the latest laboratory examinations of pre-surgery within 7 days were included, providing 118,823 data points. 39 predictive factors related to the RBCs transfusion were identified. Random forest model was selected to predict the required PBV of RBCs with 72.9% accuracy and strikingly improved the accuracy by 30.4% compared with surgeons experience, where 90% of data was used for training. We tested and demonstrated that both the data-driven models and the random forest model achieved higher accuracy than surgeons experience. Furthermore, we developed a computational tool, PTRBC, to precisely estimate the required PBV in surgical patients and we believe this tool will find more applications in assisting clinician decisions, not only confined to making accurate pre-surgery blood requirement predicting.