bluuebunny/crossref_metadata_2025 huggingface dataset:
Host Suitability of Cover Crops to the Root-Lesion Nematode Pratylenchus penetrans Associated with Potato
Authors: Neupane Kamal , Yan Guiping
Published: December 2022

Nonhost or poor host cover crops can provide an alternative method for nematode management. A total of 25 cover crop species/cultivars, along with three controls were evaluated in greenhouse experiments for their host suitability to the root-lesion nematode Pratylenchus penetrans. Trials were conducted in a completely randomized design using nematode-infested soil and terminated 3 months after planting. Nematodes were extracted from the roots and soil of each crop to determine their final population densities, reproductive factor (Rf = final population density/initial population density), and distributions in the soil and root habitats. Reproductive factor was used to categorize the host suitability of crops. Faba bean cv. Petite produced the greatest nematode population density in all trials, whereas only alfalfa cv. Bullseye constantly demonstrated the poor host ability to P. penetrans. Annual ryegrass, winter rye cv. ND Dylan, and white proso millet also showed poor hosts in most trials. Five cover crops consistently maintained the population throughout the experiments, with Rf values less than 2, and the remaining tested cover crops were suitable hosts for P. penetrans. The majority of the tested cover crops had less than or equal to 30% of the final population residing in the roots after three months of growth in all the trials. This research helps us gain the knowledge on cover crops and P. penetrans interaction and will be useful for potato growers to select better cover crops and avoid susceptible hosts to manage P. penetrans in infested fields to minimize potato yield losses.
Meperidine Compared With Nitrous Oxide for Intrapartum Pain Relief in Multiparous Patients
Authors: Zuarez-Easton Sivan , Zafran Noah , Garmi Gali , Dagilayske Dorit , Inbar Shiri , Salim Raed
Published: December 2022

OBJECTIVE:

To compare the efficacy and adverse effects of intravenous meperidine and inhaled nitrous oxide for intrapartum analgesia in multiparous patients.

METHODS:

This randomized controlled trial was conducted in the delivery ward of a university teaching medical center in Afula, Israel. Multiparous patients with term, singleton pregnancies who were in labor were randomized in a 1:1 ratio to 50 mg intravenous meperidine or inhaled nitrous oxide. The primary outcome was pain intensity 20–30 minutes after analgesic administration, measured on a visual analog scale (VAS) from 0 to 10 cm. Secondary outcomes included the need for additional analgesia, labor length, delivery mode, patient satisfaction, and maternal and neonatal adverse effects. To detect a 1-cm (±2.6) difference in VAS score between the groups, 214 total participants were needed to achieve 80% power with an alpha of 0.05.

RESULTS:

From August 2016 through May 2019, 214 participants were enrolled. Fourteen were excluded after randomization. Of the 200 analyzed, 102 received nitrous oxide, and 98 received intravenous meperidine. Demographic and obstetric variables were comparable between the two groups. The VAS score 20–30 minutes after analgesic administration did not differ between the groups (7.7±2.3 cm and 7.6±2.7 cm in the nitrous oxide and meperidine groups, respectively, P=.89). There were no significant differences between the groups in the rate of additional analgesic use, labor length, delivery mode, Apgar scores, rate of breastfeeding, patient satisfaction, or maternal and neonatal adverse effects.

CONCLUSION:

Pain intensity was comparable in multiparous patients 20–30 minutes after administration of meperidine and nitrous oxide. Adverse effects were also comparable.

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov, NCT02783508.
Fasting Compared With Fed and Oral Intake Before the 1-Hour Oral Glucose Tolerance Test
Authors: Sperling Meryl M. , Leonard Stephanie A. , Miller Sarah E. , Hurtado Janet , El-Sayed Yasser Y. , Herrero Tiffany , Faig Jeffrey , Carter Susan , Blumenfeld Yair J.
Published: December 2022

OBJECTIVE:

To evaluate the effect of fasting compared with eating before the 1-hour oral glucose tolerance test (OGTT) on gestational diabetes mellitus (GDM) screening results.

METHODS:

In a single-center, prospective randomized trial, participants were randomized to: 1) fasting for 6 or more hours or 2) oral intake (“fed”) within 2 hours of the 50-g, 1-hour OGTT. The 1-hour OGTT was administered after 24 weeks of gestation. A positive screen result was defined as a serum glucose level of 140 mg/dL or higher. Protocol adherence was assessed by a survey administered immediately after the OGTT. We planned to enroll 100 participants in each group to detect an absolute difference of 20 percentage points or more on the 1-hour OGTT screen-positive rate using Fisher exact test, assuming an estimated screen-positive rate of 45% in the fasting and 25% in the fed group and 10% attrition, with a two-sided α=0.05, power=0.8. The primary outcome was the 1-hour OGTT screen-positive rate. Secondary outcomes included mean 1-hour OGTT glucose values, GDM diagnosis, maternal and neonatal outcomes, and patient perceptions regarding the 1-hour OGTT.

RESULTS:

From November 2020 through April 2021, 200 participants were randomized. One hundred ninety-five completed the 1-hour OGTT (97 fasting, 98 fed). Participant surveys confirmed 97.9% (n=95) adherence to the fasting and 91.8% (n=90) adherence to the fed groups. The screen-positive rate was significantly higher in the fasting than the fed group (32.0% vs 13.3%, respectively, P=.002), as was the mean glucose value (127.7 mg/dL vs 113.3 mg/dL, P=.002). The incidence of GDM in the fasting group was 12.4% (n=12) and in the fed group was 5.1% (n=5) (P=.08). There were no significant differences in maternal or neonatal outcomes.

CONCLUSION:

Fasting for 6 or more hours doubled the incidence of a positive 1-hour OGTT result when compared with eating within 2 hours of the test.

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov, NCT04547023.
Timing of Prone Positioning During Venovenous Extracorporeal Membrane Oxygenation for Acute Respiratory Distress Syndrome
Authors: Giani Marco , Rezoagli Emanuele , Guervilly Christophe , Rilinger Jonathan , Duburcq Thibault , Petit Matthieu , Textoris Laura , Garcia Bruno , Wengenmayer Tobias , Bellani Giacomo , Grasselli Giacomo , Pesenti Antonio , Combes Alain , Foti Giuseppe , Schmidt Matthieu ,   for the European Prone positioning During Extracorporeal Membrane Oxygenation (EuroPronECMO) Investigators
Published: December 2022

OBJECTIVES:

To assess the association of timing to prone positioning (PP) during venovenous extracorporeal membrane oxygenation (V-V ECMO) with the probability of being discharged alive from the ICU at 90 days (primary endpoint) and the improvement of the respiratory system compliance (Cpl,rs).

DESIGN:

Pooled individual data analysis from five original observational cohort studies.

SETTING:

European extracorporeal membrane oxygenation (ECMO) centers.

PATIENTS:

Acute respiratory distress syndrome (ARDS) patients who underwent PP during ECMO.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Time to PP during V-V ECMO was explored both as a continuous and a categorical variable with Cox proportional hazard models. Three hundred patients were included in the analysis. The longer the time to PP during V-V ECMO, the lower the adjusted probability of alive ICU discharge (adjusted hazard ratio [HR] 0.90 for each day increase; 95% CI, 0.87–0.93). Two hundred twenty-three and 77 patients were included in the early PP (≤ 5 d) and late PP (> 5 d) groups, respectively. The cumulative 90-day probability of being discharged alive from the ICU was 61% in the early PP group vs 36% in the late PP group (log-rank test, p <0.001). This benefit was maintained after adjustment for confounders (adjusted HR, 2.52; 95% CI, 1.66–3.81; p <0.001). In the early PP group, PP was associated with a significant improvement of Cpl,rs (4 ± 9 mL/cm H2O vs 0 ± 12 in the late PP group, p=0.038).

CONCLUSIONS:

In a large cohort of ARDS patients on ECMO, early PP during ECMO was associated with a higher probability of being discharged alive from the ICU at 90 days and a greater improvement of Cpl,rs.
Prediction of Difficult Laryngoscopy Using Ultrasound: A Systematic Review and Meta-Analysis
Authors: Bhargava Vidit , Rockwell Nicholas A. , Tawfik Daniel , Haileselassie Bereketeab , Petrisor Cristina , Su Erik
Published: December 2022

OBJECTIVES:

Evaluate associations between ultrasound measures and difficult laryngoscopy.

DATA SOURCES:

MEDLINE, Embase, Google Scholar, Web of Science, and the Cochrane Library were searched using MeSH terms and keywords.

STUDY SELECTION:

Studies published in English describing the use of airway ultrasound for identifying difficult laryngoscopy, with sufficient data to calculate sensitivity and specificity using 2 × 2 tables.

DATA EXTRACTION:

We assigned the described indices of airway dimension to one of three domains based on methodology characteristics: anterior tissue thickness domain, anatomical position domain, and oral space domain. We then performed a bivariate random-effects meta-analysis, deriving pooled sensitivity, specificity, diagnostic odds ratio, positive likelihood ratio, and negative likelihood ratio estimates. We assessed risks of bias using Quality Assessment of Diagnostic Accuracy Studies-2 analysis.

DATA SYNTHESIS:

Thirty-three studies evaluating 27 unique indices were included in the meta-analysis. The ultrasound protocols of the included studies were heterogeneous. Anterior tissue thickness demonstrated a pooled sensitivity of 76% (95% CI, 71–81%), specificity of 77% (95% CI, 72–81%), and an area under the receiver operating characteristic curve (AUROC) of 0.83 (95% CI, 0.80–0.86). Anatomical position demonstrated a pooled sensitivity of 74% (95% CI, 61–84%), specificity of 86% (95% CI, 78–91%), and an AUROC of 0.87 (95% CI, 0.84–0.90). Oral space demonstrated a pooled sensitivity of 53% (95% CI, 0.36–0.69), specificity of 77% (95% CI, 0.67–0.85), and an AUROC of 0.73 (95% CI, 0.69–0.77).

CONCLUSIONS:

Airway ultrasound metrics associate with difficult laryngoscopy in three domains: anterior tissue thickness, anatomic position, and oral space. An assessment instrument combining clinical and ultrasound assessments may be an accurate screening tool for difficult laryngoscopy.
Endovascular Management of Aortic Arch Diseases: Current Status and Future Trends
Authors: Shu Chang , Li Jiehua , Luo Mingyao , Li Quanming , Fang Kun
Published: December 2022

Treatment of aortic arch (AA) diseases is challenging for surgeons. Conventional open surgery remains the “gold standard” but is associated with significant morbidity and mortality despite improvements in techniques. In the last 2 decades, thoracic endovascular aortic repair (TEVAR) has become the first-line treatment for diseases of the descending aorta, and its indications have expanded gradually. Various strategies have been proposed to preserve supra-aortic branches in TEVAR: hybrid technique, chimney technique, fenestration technique (including custom-made fenestrated or “scalloped” stent grafts, in situ fenestration, and physician-modified fenestration), and branched stent grafts. Though acceptable outcomes of endovascular aortic repair have been documented, the evidence regarding its long-term safety and efficacy is lacking, and concerns remain about the risk of cerebrovascular events, retrograde type-A dissection, endoleaks, and branch occlusion. This review discusses the current status and progress of endovascular repair of the AA, and looks toward future trends. We believe that multidisciplinary collaboration of a “HENDO” team (professionals in hybrid repair, endovascular repair, open surgery, cardiovascular anesthesia, and genetics) is essential for future repair of the AA to provide the optimal treatment.
Developmental language disorders in preschool children after high exposure to perfluoroalkyl substances from contaminated drinking water in Ronneby, Sweden
Authors: Stübner Charlotte , Ebel Matilda , Jakobsson Kristina , Gillberg Christopher , Nielsen Christel , Miniscalco Carmela
Published: December 2022

Background:

There are indications that early-life exposure to perfluoroalkyl substances (PFAS) can impact neurodevelopment, but results are inconclusive. The objective was to investigate if high early-life exposure to primarily perfluorohexanesulfonic acid (PFHxS) and perfluorooctanesulfonic acid (PFOS) increases the risk of developmental language disorder in children up to seven years of age.

Methods:

A register-based cohort of all children born 1998–2013 in Blekinge county, Sweden, was studied. Maternal residential history, that is, with or without highly PFAS-contaminated drinking water, during the 5-year period before childbirth was used as a proxy for early-life exposure. Exposure was categorized as high (n = 646), intermediate (n = 1,650), or background (n = 9,599). We used Cox proportional hazards regression to estimate hazard ratios (HR) for (1) referral to a speech- and language pathologist after routine screening at Child Health Services, and (2) subsequent language disorder diagnosis after clinical assessment. Models were adjusted for parity, maternal age, education level, and smoking, and explored effect modification by sex.

Results:

In children from the high-exposed area, the adjusted HR for referral was 1.23 (95% CI = 1.03, 1.47) and 1.13 (95% CI = 0.97, 1.56) for subsequent diagnosis. There was no increased risk in the intermediate exposure category.

Conclusion:

Children, particularly girls, with high exposure had an increased risk of both referral and confirmed developmental language disorder. Further research is needed on PFAS in the context of general neurodevelopment, for which language development is a proxy.
Prescription Habits of Scleral Lenses for the Management of Corneal Irregularity and Ocular Surface Disease Among Scleral Lens Practitioners
Authors: Shorter Ellen , Fogt Jennifer , Nau Cherie , Harthan Jennifer , Nau Amy , Schornack Muriel
Published: December 2022

Objectives:

To describe prescribing patterns of therapeutic scleral lenses (SLs) in the management of corneal irregularity and ocular surface disease among practitioners who prescribe SLs.

Methods:

Participants ranked treatment options for corneal irregularity and ocular surface disease in the order they would generally consider using them in an electronic survey. Median rank score for each option is reported, along with the percentage of participants assigning first place ranking to each option. The percentage of participants assigning first, second, or third place ranking to each option is also reported.

Results:

Seven hundred and seventy-eight practitioners participated. Scleral lenses are most frequently considered as the first choice for the management of corneal irregularity based on overall median rank, followed by corneal rigid lenses (rigid gas-permeable [RGPs]). Scleral lenses were the first choice of 42% of participants, followed by RGPs (20%). For ocular surface disease, lubricant drops are most frequently used first, followed by meibomian gland expression, topical cyclosporine or lifitegrast, topical steroids, punctal plugs, and SLs, respectively. Lubricant drops were the first therapeutic option considered for ocular surface disease by 63% of participants and 45% ranked SLs as their sixth, seventh or eighth treatment based on median overall rank.

Conclusions:

Scleral lenses were identified as the first option for management of corneal irregularity more frequently than RGPs. Scleral lenses are considered for management of ocular surface disease before surgical intervention but after meibomian gland expression, punctal occlusion, and topical medical therapy are attempted.
The Role of the Hand Surgery Consultant in the Care of the Baseball Athlete
Authors: Graham Thomas J.
Published: December 2022

The approach to the care of baseball athletes and organizations is influenced by 2 factors that distinguish it from other sports: the number of contests and the number of players. America’s pastime is a marathon that can (if successful in the regular season and postseason play) stretch over a 10-months, 162+-game schedule. In addition, unlike other major North American sports, baseball’s “feeder system” is the highly-structured Minor League Baseball. This is in contradistinction to caring for 15 basketball players who arrive at the professional level through collegiate (or even high school) play or 20 hockey players that may have had an NCAA experience or come through the Junior Leagues in Canada. Even though a 53-man football roster can keep a Hand Surgery Consultant busy, it is still a limited professional level cohort that is one-third to one-fourth of the size of baseball’s and is played across less than 20 contests. Granted, every sport has its own culture—which is why we have developed this format for this publication—but planning for the scope of baseball care is also influenced by the unique pace and intensity of the interactions, that is why it is called a “clubhouse,” rather than a “locker room”. With these fundamentals shared, let us expand on what our experience has taught us about the care for athletes that are engaged in batting, throwing, receiving, and colliding on the diamond.
The Role of the Hand Surgery Consultant in the Care of the Hockey Athlete
Authors: French Rodney J.
Published: December 2022

Ice hockey is a high-speed sport played on a slippery ice surface, using sharp skate blades, rigid sticks with a hard rubber puck, and allowing full-force physical contact that includes body checking and fighting. Although many of the same injuries to the hand and wrist occur that are seen in other sports, there is a higher frequency of certain injuries in the hockey athlete due to the forces involved, the way the hockey stick is gripped, torqued, and used, and the fact that players can slash one another with their sticks. Beyond timely and accurate management of the injury itself, the role of the consultant hand surgeon in hockey encompasses mastery of the intangible skills in the art and humanity of medical care. Injury to the hockey athlete sets in motion a dynamic process that involves many stakeholders who each require your knowledge of how this will affect the hockey athlete’s immediate and long-term health, how long they may be out of competition, and the kind of treatments, splints and equipment modifications that could help foster the earliest return-to-play in a safe manner. The consultant hand surgeon needs the ability to communicate information at a high level to team physicians and trainers while remaining nimble enough to simplify that information for general managers, coaches, agents, and athletes. The role demands commitment in time and flexibility, remaining open to gray areas in treatment options, possessing a creative mindset for problem-solving, and the ability to quickly assimilate vast amounts of information to provide a risk assessment of short and long-term implications the injury presents to both the player and the team.
Cancer Immunology: Immune Escape of Tumors—Expression and Regulation of HLA Class I Molecules and Its Role in Immunotherapies
Authors: Wang Yuan , Jasinski-Bergner Simon , Wickenhauser Claudia , Seliger Barbara
Published: December 2022

The addition of “avoiding immune destruction” to the hallmarks of cancer demonstrated the importance of cancer immunology and in particular the role of immune surveillance and escape from malignancies. However, the underlying mechanisms contributing to immune impairment and immune responses are diverse. Loss or reduced expression of the HLA class I molecules are major characteristics of human cancers resulting in an impaired recognition of tumor cells by CD8+ cytotoxic T lymphocytes. This is of clinical relevance and associated with worse patients outcome and limited efficacy of T-cell-based immunotherapies. Here, we summarize the role of HLA class I antigens in cancers by focusing on the underlying molecular mechanisms responsible for HLA class I defects, which are caused by either structural alterations or deregulation at the transcriptional, posttranscriptional, and posttranslational levels. In addition, the influence of HLA class I abnormalities to adaptive and acquired immunotherapy resistances will be described. The in-depth knowledge of the different strategies of malignancies leading to HLA class I defects can be applied to design more effective cancer immunotherapies.
Resident Perceptions of Continuity Clinic Patient Metrics Differ From EHR Data: Pilot Use of Population Health Dashboards
Authors: Smith Brandon M. , Kuryla Christine L. , Shilkofski Nicole A. , Hughes Helen K. , Wheeler Noah J. , Tschudy Megan M. , Solomon Barry S. , Kim Julia M.
Published: December 2022

Background and Objectives:

Population health management (PHM) dashboards using electronic health record (EHR) data can teach trainees about the population they serve while also delivering data on their clinical practice. Yet, few studies have demonstrated their use. In this pilot study, we assessed baseline resident perceptions of population health metrics for continuity clinic panels by comparing resident estimates with EHR-reported values delivered by individualized PHM dashboards.

Methods:

A descriptive, comparative study was conducted at a primary continuity clinic site for pediatric residents in January 2018. Residents were surveyed about population health metrics for their patient panels, including demographics, utilization, and medical diagnoses. We compared resident estimates to corresponding EHR-reported values using 2-tailed paired t tests.

Results:

A total of 42 out of 55 eligible residents (76%) completed the survey. Compared with EHR-reported values, residents estimated higher percentages of emergency department utilization (22.1% vs 10.3%, P < .01) and morbidity, including medical complexity (15.6% vs 5.9%, P < .01), overweight (38.1% vs 11.7%, P < .01), obesity (20.5% vs 15.8%, P = .02), and asthma (34.6% vs 21.4%, P < .01).

Conclusions:

In this pilot study of PHM dashboards, resident perceptions of continuity clinic population health metrics did not align with EHR data. Estimates were higher for measures of utilization and morbidity. PHM dashboards may help trainees better understand their patient populations and serve as a consistent source of objective practice data. However, further research and investment is needed to evaluate dashboard implementation and impact on trainee and patient outcomes.
Local/Regional Recurrence Rates After Breast-Conserving Therapy in Patients Enrolled in Legacy Trials of the Alliance for Clinical Trials in Oncology (AFT-01)
Authors: Schumacher Jessica R. , Wiener Alyssa A. , Greenberg Caprice C. , Hanlon Bret , Edge Stephen B. , Ruddy Kathryn J. , Partridge Ann H. , Le-Rademacher Jennifer G. , Yu Menggang , Vanness David J. , Yang Dou-Yan , Havlena Jeffrey , Strand Carrie , Neuman Heather B.
Published: December 2022

Objective:

We sought to evaluate local/regional recurrence rates after breast-conserving surgery in a cohort of patients enrolled in legacy trials of the Alliance for Clinical Trials in Oncology and to evaluate variation in recurrence rates by receptor subtype.

Background:

Multiple randomized controlled trials have demonstrated equivalent survival between breast conservation and mastectomy, albeit with higher local/regional recurrence rates after breast conservation. However, absolute rates of local/regional recurrence have been declining with multi-modality treatment.

Methods:

Data from 5 Alliance for Clinical Trials in Oncology legacy trials that enrolled women diagnosed with breast cancer between 1997 and 2010 were included. Women who underwent breast-conserving surgery and standard systemic therapies (n=4,404) were included. Five-year rates of local/regional recurrence were estimated from Kaplan-Meier curves. Patients were censored at the time of distant recurrence (if recorded as the first recurrence), death, or last follow-up. Multivariable Cox proportional hazards models were used to identify factors associated with time to local/regional recurrence, including patient age, tumor size, lymph node status, and receptor subtype.

Results:

Overall 5-year recurrence was 4.6% (95% CI=4.0-5.4%). Five-year recurrence rates were lowest in those with ER+ or PR+ tumors (Her2+ 3.4% [95% CI 2.0-5.7%], Her2- 4.0% [95% CI 3.2-4.9%]) and highest in the triple-negative subtype (7.1% [95% CI 5.4-9.3%]). On multivariable analysis, increasing nodal involvement and triple-negative subtype were positively associated with recurrence (P<0.0001).

Conclusions:

Rates of local/regional recurrence after breast conservation in women with breast cancer enrolled in legacy trials of the Alliance for Clinical Trials in Oncology are significantly lower than historic estimates. This data can better inform patient discussions and surgical decision-making.
Trends in Surgeon Burnout in the US and Canada: Systematic Review and Meta-Regression Analysis
Authors: Etheridge James C , Evans Devon , Zhao Lily , Ibrahim Nourah , Wick Elizabeth C , Freischlag Julie A , Brownstein Michelle R
Published: December 2022

BACKGROUND:

Burnout among surgeons is increasingly recognized as a crisis. However, little is known about changes in burnout prevalence over time. We evaluated temporal trends in burnout among surgeons and surgical trainees of all specialties in the US and Canada.

STUDY DESIGN:

We systematically reviewed MEDLINE, Embase, and PsycINFO for studies assessing surgeon burnout from January 1981 through September 2021. Changes in dichotomized Maslach Burnout Inventory scores and mean subscale scores over time were assessed using multivariable random-effects meta-regression.

RESULTS:

Of 3,575 studies screened, 103 studies representing 63,587 individuals met inclusion criteria. Publication dates ranged from 1996 through 2021. Overall, 41% of surgeons met criteria for burnout. Trainees were more affected than attending surgeons (46% vs 36%, p = 0.012). Prevalence remained stable over the study period (−4.8% per decade, 95% CI −13.2% to 3.5%). Mean scores for emotional exhaustion declined and depersonalization declined over time (−4.1 per decade, 95% CI −7.4 to −0.8 and −1.4 per decade, 95% CI −3.0 to −0.2). Personal accomplishment scores remained unchanged. A high degree of heterogeneity was noted in all analyses despite adjustment for training status, specialty, practice setting, and study quality.

CONCLUSIONS:

Contrary to popular perceptions, we found no evidence of rising surgeon burnout in published literature. Rather, emotional exhaustion and depersonalization may be decreasing. Nonetheless, burnout levels remain unacceptably high, indicating a need for meaningful interventions across training levels and specialties. Future research should be deliberately designed to support longitudinal integration through prospective meta-regression to facilitate monitoring of trends in surgeon burnout.
Effect of Present at Time of Surgery on Unadjusted and Risk-Adjusted Postoperative Complication Rate
Authors: Bronsert Michael R , Henderson William G , Colborn Kathryn L , Dyas Adam R , Madsen Helen J , Zhuang Yaxu , Lambert-Kerzner Anne , Meguid Robert A
Published: December 2022

BACKGROUND:

Present at the time of surgery (PATOS) is an important measure to collect in postoperative complication surveillance systems because it may affect a patient’s risk of a subsequent complication and the estimation of postoperative complication rates attributed to the healthcare system. The American College of Surgeons (ACS) NSQIP started collecting PATOS data for 8 postoperative complications in 2011, but no one has used these data to quantify how this may affect unadjusted and risk-adjusted postoperative complication rates.

STUDY DESIGN:

This study was a retrospective observational study of the ACS NSQIP database from 2012 to 2018. PATOS data were analyzed for the 8 postoperative complications of superficial, deep, and organ space surgical site infection; pneumonia; urinary tract infection; ventilator dependence; sepsis; and septic shock. Unadjusted postoperative complication rates were compared ignoring PATOS vs taking PATOS into account. Observed to expected ratios over time were also compared by calculating expected values using multiple logistic regression analyses with complication as the dependent variable and the 28 nonlaboratory preoperative variables in the ACS NSQIP database as the independent variables.

RESULTS:

In 5,777,108 patients, observed event rates for each outcome were reduced by between 6.1% (superficial surgical site infection) and 52.5% (sepsis) when PATOS was taken into account. The observed to expected ratios were similar each year for all outcomes, except for sepsis and septic shock in the early years.

CONCLUSIONS:

Taking PATOS into account is important for reporting unadjusted event rates. The effect varied by type of complication—lowest for superficial surgical site infection and highest for sepsis and septic shock. Taking PATOS into account was less important for risk-adjusted outcomes (observed to expected ratios), except for sepsis and septic shock.
Immunological and Clinico-Molecular Features of Tumor Border Configuration in Colorectal Cancer
Authors: Sonal Swati , Deshpande Vikram , Ting David T , Neyaz Azfar , Pankaj Amaya , Taylor Martin S , Dinaux Anne M , Leijssen Lieve GJ , Boudreau Chloe , Berger David L
Published: December 2022

INTRODUCTION:

Infiltrating tumor border configuration (ITBC) portends a poor prognosis compared with pushing tumor border configuration (PTBC) in colorectal cancer. The tumor and its surrounding immune microenvironment of tumor border configuration is not well-characterized. We aim to elucidate the differences in expression of molecular markers between the 2 groups using tissue microarray (TMA).

STUDY DESIGN:

Immunohistochemistry was performed on TMAs of surgical pathology specimens obtained from colorectal cancer patients consecutively operated at our institution from 2004 to 2015. TMAs were stained for immune cells (CD8, FOXP3, LAG3, PU1, CD163, and PDL1); HLA II, beta 2 microglobulin, and HC10 on tumor cells; BRAFV600E mutation; and DNA mismatch repair proteins (MMR) status. Patients who received neoadjuvant therapy were excluded.

RESULTS:

There were 646 tumors with ITBC and 310 tumors with PTBC. There was a significantly lower expression (p < 0.05) of immune components, namely CD8, FOXP3, LAG3, PU1, PDL1 immune cells, and Beta-2 Microglobulin on tumor cells in the tumors with ITBC compared with PTBC, except CD163 immune cells, and HC10 and HLAII on tumor cells. Tumors with ITBC were less likely to be associated with BRAFV600E mutations and deficient MMR proteins (p < 0.001). On analyzing MMR-proficient tumors separately, we could not find any difference in the expression of any molecular marker (including BRAF), except a lower expression of PDL1 immune cells in tumors with ITBC (p < 0.001).

CONCLUSIONS:

Colorectal tumors with ITBC are associated with a generalized low immune microenvironment and low rates of BRAFV600E mutation compared with tumors with PTBC. However, the molecular expression of tumor border configuration seems confounded by the MMR molecular signature. MMR-proficient colorectal tumors with ITBC are associated with a lower expression of only PDL1 immune cells among all immune markers examined.
Ligation of Intersphincteric Fistulous Tract vs Endorectal Advancement Flap for High-Type Fistula in Ano: A Randomized Controlled Trial
Authors: Kumar Pankaj , Sarthak Siddhant , Singh Pradeep K , Mishra Tushar S , Sasmal Prakash K
Published: December 2022

BACKGROUND:

This study aimed to compare the postoperative outcomes and success rate of the endorectal advancement flap and ligation of intersphincteric fistulous tract (LIFT) in high-type fistula in ano.

STUDY DESIGN:

This randomized control trial included patients with high-type fistula in ano of cryptoglandular origin. The primary endpoint was complete fistula healing at the end of 6 months. However, the patients were followed up for 2 years. Other parameters studied were perioperative complications, duration of surgery, postoperative pain, hospital stay in hours, continence, and quality of life at 6 months.

RESULTS:

A total of 84 patients were recruited (42 in each group). The healing rate in the LIFT arm was better than that in the endorectal advancement flap arm (76.2.% vs 54.7%, p = 0.039). Four patients in the endorectal advancement flap group and two in the LIFT group had flatus incontinence at the end of 6 months, but all were continent at 2 years. At the end of the first week, the Visual Analog Scale score and quality of life at 6 months were better in the LIFT arm (3.7 ± 1.16 vs 4.7 ± 0.81 and 0.7 vs 0.6, p < 0.05). The mean duration of surgery was significantly less in the LIFT group (46.43 ± 9.32 vs 89.29 ± 10.90 minutes). None had any postoperative complications, and >80% were discharged within 24 hours.

CONCLUSIONS:

The shorter operative duration, better quality of life at 6 months, and higher healing rate make LIFT a superior treatment option for high fistula in ano. However, studies with a large sample size will be needed to verify these results.
Using Right-Sided Roll to Improve Reliability of Focused Assessment with Sonography in Trauma: An Eastern Association for the Surgery of Trauma Multicenter Prospective Study
Authors: Cibulas Shumway Megan , Granet Jason , Solomon Rachele J , Parreco Joshua P , Lee Seong K , Pigneri Danielle A ,   for the FASTeR Study Group
Published: December 2022

BACKGROUND:

The Focused Assessment Sonography in Trauma (FAST) examination is the standard of care for detecting hemoperitoneum in hypotensive blunt trauma patients. A pilot study demonstrated earlier identification of intra-abdominal fluid via FAST after right-sided roll (FASTeR) when compared with the standard FAST. The purpose of this study was to evaluate this phenomenon prospectively in hypotensive blunt trauma patients.

STUDY DESIGN:

An Eastern Association for the Surgery of Trauma–approved multicenter prospective trial was performed June 2016 to October 2020 at 8 designated trauma centers. Hypotensive adult blunt trauma patients were included. A traditional FAST examination was performed. After this, the secondary survey logroll for back examination was standardized to the patient’s right side. A repeat supine right upper quadrant ultrasound view was obtained. The presence or absence of hemoperitoneum was confirmed by CT scan or intraoperative findings. FAST and FASTeR were compared using receiver operating characteristics. The area under the curve was calculated.

RESULTS:

A total of 182 patients met inclusion criteria. A total of 65 patients (35.7%) had hemoperitoneum on CT scan or intraoperative findings. The sensitivity of FASTeR was 47.7%, and of FAST was 40.0% (p = 0.019). The receiver operating characteristics area under the curve of the FASTeR examination was 0.717 vs 0.687 for the FAST examination (p = 0.091).

CONCLUSIONS:

Addition of a right upper quadrant view after right-sided roll does improve the sensitivity of the FAST examination while maintaining the standard positive predictive value. We demonstrate a trend that does not reach statistical significance about the overall accuracy. This multicenter prospective trial was underpowered to reveal a statistically significant difference in the overall accuracy as measured by the receiver operating characteristics area under the curve.
Role of IL4 and GMCSF in Predicting Survival in Esophageal Cancer
Authors: Rebernick Ryan J , Bell Hannah N , Bauer Tyler M , McEwen Dyke , Werkman Douglas F , Chang Andrew C , Lin Jules , Reddy Rishindra M , Kresty Laura , Lagisetty Kiran
Published: December 2022

BACKGROUND:

Esophageal cancer (EC) originates in the setting of chronic inflammation. Although previous studies have sought to understand the role of inflammatory signaling in EC, the effect of these immunologic changes on patient outcomes remains understudied. This study’s objective was to identify relationships between cytokine levels and prognosis in a mixed cohort of esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC) patients.

STUDY DESIGN:

A total of 37 serum cytokines were profiled at the time of resection using multiplex ELISA in 47 patients (42 esophageal adenocarcinoma, 5 esophageal squamous cell carcinoma). Cytokine levels were median-binarized and assessed using Cox regression models. Findings were validated at the RNA level using The Cancer Genome Atlas EC cohort (81 esophageal adenocarcinoma, 81 esophageal squamous cell carcinoma).

RESULTS:

Univariable analysis revealed high serum interleukin 4 (IL4) and granulocyte-macrophage colony-stimulating factor (GMCSF) were negatively associated with overall survival (p = 0.046, p = 0.040). Multivariable analysis determined both high serum IL4 or high serum GMCSF were negatively associated with survival independent of important clinical factors (hazard ratio [HR] 7.55, p < 0.001; HR 5.24, p = 0.001). These findings were validated at the RNA level in The Cancer Genome Atlas EC cohort, where multivariable analysis identified high IL4 expression, high CSF2 expression (encodes GMCSF), and advanced pathologic stage as independent negative predictors of survival when controlled for clinical factors (HR 2.35, p = 0.012; HR 1.97, p = 0.040).

CONCLUSIONS:

These results show that high IL4/GMCSF levels are negatively associated with survival in EC. These relationships are independent of pathologic stage and are identified across modalities, histologic subtypes, and the presence/absence of neoadjuvant therapy.
Mass Dynamics 2.0: An improved modular web-based platform for accelerated proteomics insight generation and decision making
Authors: Quaglieri Anna , Bloom Joseph , Triantafyllidis Aaron , Green Bradley , Condina Mark R. , Ngov Paula Burton , Infusini Giuseppe , Webb Andrew I.
Published: December 2022

Data processing is essential to reliably generate knowledge from proteomics studies. The complexity of the proteomics data, as well as the ability of research teams to adopt complex analysis pipelines, have proven to be an obstacle to effective collaboration and more efficient biological insight generation.

Here, we introduce MD 2.0, a cloud- and web-based platform for quantitative proteomics data, which implements a novel analysis workspace where statistical analyses, visualizations, and external knowledge generation are integrated into a modular framework. This modularity enables researchers the flexibility to test different hypotheses, and customize and template complex proteomics analyses, thereby expediting insight generation for complex datasets. The extensible MD 2.0 environment has been built with a scalable architecture to allow rapid development of future analysis modules and enhanced tools for remote collaboration, like experiment sharing and a live chat capability.

The new drag-and-drop modules allow researchers to easily and quickly assess different aspects of an experiment, including quality control, differential expression and enrichment analysis. The modularity of MD 2.0 lays the foundation to support broader community-based analytical template generation and optimized sharing and collaboration between proteomics experts and biologists, thereby accelerating research teams’ abilities to extract knowledge from complex proteomics datasets.
Application of Aligned-UMAP to longitudinal biomedical studies
Authors: Dadu Anant , Satone Vipul K. , Kaur Rachneet , Koretsky Mathew J. , Iwaki Hirotaka , Qi Yue A. , Ramos Daniel M. , Avants Brian , Hesterman Jacob , Gunn Roger , Cookson Mark R. , Ward Michael E. , Singleton Andrew B , Campbell Roy H , Nalls Mike A , Faghri Faraz
Published: December 2022

Longitudinal multi-dimensional biological datasets are ubiquitous and highly abundant. These datasets are essential to understanding disease progression, identifying subtypes, and drug discovery. Discovering meaningful patterns or disease pathophysiologies in these datasets is challenging due to their high dimensionality, making it difficult to visualize hidden patterns. Several methods have been developed for dimensionality reduction, but they are limited to cross-sectional datasets. Recently proposed Aligned-UMAP, an extension of the UMAP algorithm, can visualize high-dimensional longitudinal datasets. In this work, we applied Aligned-UMAP on a broad spectrum of clinical, imaging, proteomics, and single-cell datasets. Aligned-UMAP reveals time-dependent hidden patterns when color-coded with the metadata. We found that the algorithm parameters also play a crucial role and must be tuned carefully to utilize the algorithm’s potential fully.

Altogether, based on its ease of use and our evaluation of its performance on different modalities, we anticipate that Aligned-UMAP will be a valuable tool for the biomedical community. We also believe our benchmarking study becomes more important as more and more high-dimensional longitudinal data in biomedical research becomes available.

Highlights

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explored the utility of Aligned-UMAP in longitudinal biomedical datasets

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offer insights on optimal uses for the technique

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provide recommendations for best practices

In Brief

High-dimensional longitudinal data is prevalent yet understudied in biological literature. High-dimensional data analysis starts with projecting the data to low dimensions to visualize and understand the underlying data structure. Though few methods are available for visualizing high dimensional longitudinal data, they are not studied extensively in real-world biological datasets. A recently developed nonlinear dimensionality reduction technique, Aligned-UMAP, analyzes sequential data. Here, we give an overview of applications of Aligned-UMAP on various biomedical datasets. We further provide recommendations for best practices and offer insights on optimal uses for the technique.
Generalizing the isothermal efficiency by using Gaussian distributions
Authors: Schneider Thomas D.
Published: December 2022

Unlike the Carnot heat engine efficiency published in 1824, an isothermal efficiency derived from thermodynamics and information theory can be applied to biological systems. The original approach by Pierce and Cutler in 1959 to derive the isothermal efficiency equation came from Shannon’s channel capacity of 1949 and from Felker’s 1952 determination of the minimum energy dissipation needed to gain a bit. In 1991 and 2010 Schneider showed how the isothermal efficiency equation can be applied to molecular machines and that this can be used to explain why several molecular machines are 70% efficient. Surprisingly, some macroscopic biological systems, such as whole ecosystems, are also 70% efficient but it is hard to see how this could be explained by a thermodynamic and molecular theory. The thesis of this paper is that the isothermal efficiency can be derived without using thermodynamics by starting from a set of independent Gaussian distributions. This novel derivation generalizes the isothermal efficiency equation for use at all levels of biology, from molecules to ecosystems.
The role of Absorbing Markov Chains in childhood cancer
Authors: Margarit David H. , Reale Marcela V. , Scagliotti Ariel F. , Romanelli Lilia M.
Published: December 2022

Absorbing Markov Chains are an important mathematical tool used for different applications in science. On the other hand, cancer and its metastases in children have a significant impact on health due to their degree of lethality. Therefore, the aim of this work is to model the metastatic pathways of the main childhood cancers worldwide. The probabilities of generating metastases, from a primary site to secondary and tertiary sites, were characterized by constructing a directed graph and the associated transition matrix. In addition, the time of absorption and the probabilities of absorption by each absorbing state were calculated.
Deciphering the determinants of recombinant protein yield across the human secretome
Authors: Masson Helen O. , Kuo Chih-Chung , Malm Magdalena , Lundqvist Magnus , Sievertsson Åsa , Berling Anna , Tegel Hanna , Hober Sophia , Uhlén Mathias , Grassi Luigi , Hatton Diane , Rockberg Johan , Lewis Nathan E.
Published: December 2022

Mammalian cells are critical hosts for the production of most therapeutic proteins and many proteins for biomedical research. While cell line engineering and bioprocess optimization have yielded high protein titers of some recombinant proteins, many proteins remain difficult to express. Here, we decipher the factors influencing yields in Chinese hamster ovary (CHO) cells as they produce 2165 different proteins from the human secretome. We demonstrate that variation within our panel of proteins cannot be explained by transgene mRNA abundance. Analyzing the expression of the 2165 human proteins with machine learning, we find that protein features account for only 15% of the variability in recombinant protein yield. Meanwhile, transcriptomic signatures account for 75% of the variability across 95 representative samples. In particular, we observe divergent signatures regarding ER stress and metabolism among the panel of cultures expressing different recombinant proteins. Thus, our study unravels the factors underlying the variation on recombinant protein production in CHO and highlights transcriptomics signatures that could guide the rational design of CHO cell systems tailored to specific proteins.
Alkalinity modulates a unique suite of genes to recalibrate growth and pH homeostasis
Authors: Bailey Mitylene , Hsieh En-Jung , Tsai Huei-Hsuan , Ravindran Arya , Schmidt Wolfgang
Published: December 2022

Alkaline soils pose a conglomerate of constraints to plants, restricting the growth and fitness of non-adapted species in habitats with low active proton concentrations. To thrive under such conditions, plants have to compensate for a potential increase in cytosolic pH and restricted softening of the cell wall to invigorate cell elongation in a proton-depleted environment. To discern mechanisms that aid in the adaptation to external pH, we grew plants on media with pH values ranging from 4.5 to 8.5. Growth was severely restricted at pH 4.5 and above pH 6.5, and associated with decreasing chlorophyll levels at alkaline pH. Bicarbonate treatment worsened plant performance, suggesting effects that differ from those exerted by pH as such. Transcriptional profiling of roots subjected to short-term transfer from optimal (pH 5.5) to alkaline (pH 7.5) media unveiled a large set of differentially expressed genes that were partially congruent with genes affected by low pH, bicarbonate and nitrate, but showed only a very small overlap with genes responsive to the availability of iron. Further analysis of selected genes disclosed pronounced responsiveness of their expression over a wide range of external pH values. Alkalinity altered the expression of various proton/anion co-transporters, possibly to recalibrate cellular proton homeostasis. Co-expression analysis of pH-responsive genes identified a module of genes encoding proteins with putative functions in the regulation of root growth, which appears to be conserved in plants subjected to low pH or bicarbonate. Our analysis provides an inventory of pH-sensitive genes and allows comprehensive insights into processes that are orchestrated by external pH.