bluuebunny/crossref_metadata_2025 huggingface dataset:
Colonic mucosal eosinophilia and immunohistochemical expression of COX-2 and NF-kB in patients with irritable bowel syndrome
Authors: Hassanin Taha M , Fouad Yasser , Mohamed Fatma Elzahraa , Abdel-Hafeez Ekhlas H. , Hassnine Alshymaa
Published: March 2022

Background

There is growing evidence that eosinophilic infiltration can release mediators which are harmful to the intestinal epithelium in patients with irritable bowel syndrome (IBS). Although cyclooxygenase 2 (COX-2) and nuclear factor-kappa beta (NF-kB) expression had been previously reported to increase in many inflammatory conditions, there is a paucity in data investigating their expressions in IBS. Our aim was to evaluate colonic mucosal eosinophilia and immunohistochemical expression of COX-2 and NF-kB in patients with irritable bowel syndrome.

Methods

A total of 80 patients who met the inclusion criteria of IBS based on Rome IV symptoms questionnaire were subjected to abdominal ultrasound, laboratory investigations, serum immunoglobulin E (IgE) level assessment and colonoscopic examination. Immunohistochemistry was performed to detect COX-2 and NF-kB expression in colonic biopsies obtained from IBS patients.

Results

Histopathological examination showed that 60 colonic biopsy specimens (75%) showed few mixed inflammatory cells ≤3 cells/ HPF, 12 biopsy specimens (15%) showed eosinophilic infiltration ≥25 eosinophils/HPF and 8 biopsy specimens (10%) showed severe lymphocytic infiltration and aggregation. Colonic eosinophilic infiltrate was significantly higher among patients presented with IBS-D subtype. Serum IgE was significantly higher among patients with colonic eosinophilic infiltrate than the others. In IBS-D patients, colonic mucosa showed positive expression of COX-2 and NF-kB in 52.1% and 81.25% of cases, respectively.

Conclusion

Patients with IBS -particularly IBS-D subtype- should undergo colonoscopy and biopsy to exclude underlying inflammatory pathology. Moreover, patients with positive COX-2 and NF-kB need further evaluation and follow-up.
Contribution of phosphate and FGF23 to CKD progression
Authors: Jansson Kyle P. , Yu Alan S.L. , Stubbs Jason R.
Published: March 2022

Purpose of review

Progressive forms of chronic kidney disease (CKD) exhibit kidney inflammation and fibrosis that drive continued nephron loss; however, factors responsible for the development of these common pathologic features remain poorly defined. Recent investigations suggest pathways involved in maintaining urinary phosphate excretion in CKD may be contributing to kidney function decline. This review provides an update on recent evidence linking altered phosphate homeostasis to CKD progression.

Recent findings

High dietary phosphate intake and increased serum concentrations of fibroblast growth factor 23 (FGF23) both increase urinary phosphate excretion and are associated with increased risk of kidney function decline. Recent investigations have discovered high concentrations of tubular phosphate promote phosphate-based nanocrystal formation that drives tubular injury, cyst formation, and fibrosis.

Studies presented in this review highlight important scientific discoveries that have molded our current understanding of the contribution of altered phosphate homeostasis to CKD progression. The collective observations from these investigations implicate phosphaturia, and the resulting formation of phosphate-based crystals in tubular fluid, as unique risk factors for kidney function decline. Developing a better understanding of the relationship between tubular phosphate handling and kidney pathology could result in innovative strategies for improving kidney outcomes in patients with CKD.
Percutaneous endoscopic jejunostomy: when, how, and when to avoid it
Authors: Gkolfakis Paraskevas , Arvanitakis Marianna
Published: March 2022

Purpose of review

The current review summarizes current evidence regarding the indications, contraindications, and technical aspects of placing a direct percutaneous endoscopic jejunostomy (DPEJ), as well as procedure-related and patient-related outcomes.

Recent findings

DPEJ is indicated for patients who require long-term (>4 weeks) jejunal nutrition due to existing altered foregut anatomy (e.g., previous gastrectomy) or because the gastric route is not an option (e.g., due to high risk of aspiration, intolerance, gastroparesis). DPEJ may also offer decompression of the gastrointestinal tract in cases of small bowel obstruction (e.g., peritoneal carcinomatosis). Absolute contraindications include active peritonitis, uncorrectable coagulopathy, and ongoing bowel ischemia. Technically, the ‘pull’ technique using a paediatric colonoscope will be sufficient for most cases. Recent publications demonstrate high rates of technical success (>85%), while patient outcomes do not differ among patients undergoing percutaneous endoscopic gastrostomy (PEG) and those undergoing DPEJ. Obesity is a risk factor for technical failure, while age more than 80 years, diabetes mellitus, and ongoing inflammatory status may be considered risk factors for DPEJ-associated mortality.

DPEJ is a safe and efficacious modality for long-term jejunal nutrition with an acceptable risk of mild complications. Careful patient selection and respect of preprocedural, periprocedural, and postprocedural precautions are of the utmost importance to ensuring a favourable outcome.
Are the Diagnosis and Treatment of Acute Cystitis in the Premenopausal, Pregnant, and Postmenopausal Women the Same? A Review of the Literature
Authors: Pagan Megan E. , Racher M. Luann , Phillips Amy M. , Manning Nirvana , Whittington Julie R. , Thomas Shelia , Magann Everett F.
Published: March 2022

Importance

Acute cystitis is a common condition diagnosed in women. The diagnosis and treatment of this condition change throughout a woman's life. Understanding the differences in diagnosis and treatment in premenopausal, pregnant, and postmenopausal woman increases the likelihood of treatment success and decreases risk of complications from untreated or suboptimally treated infections.

Objective

The aim of this review is to describe the incidence, risk factor, pathophysiology, diagnosis, and management of acute cystitis and the similarities and differences of these aspects of the condition in the premenopausal, pregnant, and postmenopausal woman.

Evidence Acquisition

A PubMed, Web of Science, and CINAHL search was undertaken with the years 1990 to 2020 searched.

Results

There were 393 articles identified, with 103 being the basis of review. Multiple risk factors for acute cystitis have been identified and are largely consistent throughout a woman's lifetime with few exceptions. The diagnoses by group with common diagnostic tools, such as urinalysis, vary in specificity and sensitivity between these groups. Management also varies between groups, with pregnancy having specific limitations related to drug safety in regard to possible fetal effects posed by certain medications commonly used to treat acute cystitis.

Conclusions

Acute cystitis not only varies in presentation throughout a woman's lifespan, but also in appropriate diagnosis and treatment. Treatment of acute cystitis does have some commonalities between the groups; however, there are contraindications unique to each group. These differences are paramount to not only ensuring appropriate treatment but also treatment success.

Relevance

Acute cystitis is a common condition with different diagnostic and management recommendations throughout a woman's lifespan.

Target Audience

Obstetricians and gynecologists, family physicians.

Learning Objectives

After completing this activity, the learner should be better able to evaluate published literature regarding acute cystitis in female patients; diagnose and recommend treatment for acute cystitis in premenopausal, pregnant, and postmenopausal patients; and identify the limitations and contraindications for antibiotics used to treat acute cystitis in each group.
My Baby's Movements: A Stepped-Wedge Cluster-Randomised Controlled Trial of a Fetal Movement Awareness Intervention to Reduce Stillbirths
Authors: Flenady V. , Gardener G. , Ellwood D. , Coory M. , Weller M. , Warrilow K. A. , Middleton P. F. , Wojcieszek A. M. , Groom K. M. , Boyle F.M. , East C. , Lawford H. L. S. , Callander E. , Said J. M. , Walker S. P. , Mahomed K. , Andrews C. , Gordon A. , Norman J. E. , Crowther C.
Published: March 2022

(Abstracted from BJOG 2022;129:29–41)

Decreased fetal movement (DFM) can indicate that a pregnancy is at risk for stillbirth. Maternal awareness and monitoring of fetal movement have been considered to be a simple, low-cost stillbirth prevention strategy.
Paracetamol Use During Pregnancy—A Call for Precautionary Action
Authors: Bauer Ann Z. , Swan Shanna H. , Kriebel David , Liew Zeyan , Taylor Hugh S. , Bornehag Carl-Gustaf , Andrade Anderson M. , Olsen Jørn , Jensen Rigmor H. , Mitchell Rod T. , Skakkebaek Niels E. , Jégou Bernard , Kristensen David M.
Published: March 2022

(Abstracted from Nat Rev Endocrinol 2021;17:757–766)

Paracetamol, otherwise known as acetaminophen, is the active ingredient in over 600 prescription and nonprescription analgesic and antipyretic medications. Worldwide and in the United States, more than 50% and 65% of pregnant women use acetaminophen, respectively.
Updates in Grading of Renal Cell Carcinomas Beyond Clear Cell Renal Cell Carcinoma and Papillary Renal Cell Carcinoma
Authors: Paner Gladell P. , Chumbalkar Vaibhav , Montironi Rodolfo , Moch Holger , Amin Mahul B.
Published: March 2022

The World Health Organization (WHO) recommends grading of clear cell renal cell carcinoma (RCC) and papillary RCC using the WHO/International Society of Urological Pathology (ISUP) grade, which is primarily based on nuclear features. As the spectrum of RCC continues to evolve, with more recently described subtypes in the past decade, literature evidence on grading these subtypes is limited or not available for some tumor types. Herein, we outline a pragmatic approach to the topic of grading RCC, dividing the contemporarily described RCC subtypes into 7 categories based on the potential clinical applicability of grading as a useful prognostic parameter: (1) RCC subtypes that are reasonably validated and recommended for WHO/ISUP grading; (2) RCC subtypes where WHO/ISUP is not applicable; (3) RCC subtypes where WHO/ISUP grading is potentially clinically useful; (4) inherently aggressive RCC subtypes where histologic classification itself confers an aggressive biologic potential; (5) renal epithelial tumors where WHO/ISUP grading provides potentially misleading prognostic implication; (6) renal epithelial neoplasms where low WHO/ISUP grade features are a prerequisite for accurate histologic classification; and (7) renal epithelial neoplasms with no or limited data on grading or incomplete understanding of the biologic potential. Our aim in outlining this approach is 2-fold: (a) identify the gaps in understanding and application of grading in RCC subtypes so that researchers in the field may perform additional studies on the basis of which the important pathologic function of assignment of grade may be recommended to be performed as a meaningful exercise across a wider spectrum of RCC; and (b) to provide guidance in the interim to surgical pathologists in terms of providing clinically useful grading information in RCC based on currently available clinicopathologic information.
Comparative Analysis of PRAME Expression in 127 Acral and Nail Melanocytic Lesions
Authors: Santandrea Giacomo , Valli Riccardo , Zanetti Eleonora , Ragazzi Moira , Pampena Riccardo , Longo Caterina , Lai Michela , Piana Simonetta , Cesinaro Anna M.
Published: March 2022

PRAME (PReferentially expressed Antigen in MElanoma), a cancer testis antigen expressed in low levels in gonadal, endometrial, and adrenal gland tissues, has been recently considered a valuable tool in the differential diagnosis between benign and malignant melanocytic lesions. The aim of the current study is to perform PRAME immunostaining on a large series of benign and malignant acral lesions to evaluate the reproducibility of data reported in the literature and to validate PRAME as an affordable tool in the differential diagnosis between benign and malignant acral melanocytic tumors. Immunohistochemical analysis for PRAME was performed in 127 benign and malignant acral and nail melanocytic lesions. To better correlate PRAME expression with the nature (benign vs. malignant) of the lesions, we categorized PRAME tumor cells percentage positivity and intensity in a cumulative score obtained by adding the quartile of positive tumor cells (0, 1+, 2+, 3+, 4+) to PRAME expression intensity in tumor cells (0, 1+, 2+, 3+). Adopting an arbitrary PRAME expression score of < 5 versus ≥5 resulted in a correct identification of 82.5% of benign and 87.1% of malignant lesions. PRAME immunohistochemistry demonstrated good sensitivity and specificity in the diagnosis of acral melanocytic lesions, however, in line with the previous literature, we identified a subset of challenging cases such as acral Spitz nevi, in situ melanomas, and small, thin, invasive melanomas in which PRAME did not correlate with morphologic features. This suggests that PRAME can be a valid tool to be incorporated in a diagnostic clinicopathologic algorithm, subject to morphologic characteristics.
Pumping the Periosteum: A Feasibility Study
Authors: Saulacic Nikola , Vunjak-Novakovic Gordana , Haga-Tsujimura Maiko , Nakahara Ken , Gerbaix Maude Coline , Ferrari Serge Livio
Published: March 2022

Purpose

Gradual elevation of periosteum from the bone surface is known to promote the adaptation of soft tissues and the formation of hard tissues. The aim of our study was to estimate the benefit of periosteal distraction osteogenesis (PDO) on de novo bone formation in a rat model.

Materials and Methods

After device placement, animals were allowed for a latency period of 7 days. Animals in the PDO group were subjected to distraction at a rate of 0.1 mm/d for 10 days. In the periosteal pumping (PP) group, the animals were subjected to distraction at a rate of 0.1 mm/d. The direction of distraction was alternated every 2 days. The animals were euthanized at 17, 31, and 45 days after surgery, and the samples were analyzed histologically and by microcomputed tomography.

Results

In both groups, the new bone was characterized as primary woven bone that was located at the leading edge of bone apposition. Bone volumes significantly increased throughout the observation period both in the PP group (P = 0.018) and in the PDO group (P < 0.001). The new bone was denser and more mature in the PP group than in the PDO group, and the difference was significant at the 31-day time point (P = 0.024). However, the volume of the new bone was higher in the PDO at the 45-day time point (P < 0.001).

Conclusions

We propose that the PP may be applied to enhance the osteogenic capacity of periosteum without plate elevation. Because this is only a proof-of-principle study, the alternated protocol of periosteal distraction warrants evaluation in the future studies.
The Role of Nasal Sill Correction in Secondary Cleft Rhinoplasty
Authors: Lamb Patrick , Jinka Sanjay , McNinch Neil L. , Murthy Ananth S.
Published: March 2022

Background

Evaluating outcomes after cleft rhinoplasty can be challenging because of the lack of objective measures that would lead to a more desirable outcome.

Methods

This study is a 10-year retrospective review of 30 consecutive patients who underwent secondary unilateral cleft rhinoplasty performed by a single surgeon. Subjective ratings were made using the Unilateral Cleft Lip Surgical Outcomes Evaluation (UCL SOE), which rates 4 components (nose, cupid's bow, lateral lip, and free vermillion) with a score of 0 to 2. Multiple anthropometric measurements (nostril height ratio, width ratio, medial ¼ height ratio, sill ratio, nostril area ratio, columellar angle, tip projection ratio, and nasolabial angle) were taken using a free National Institutes of Health program, ImageJ. Standardized photographs were compared at T0 (preoperatively), T1 (<6 weeks postoperatively), and T2 (>6 weeks postoperatively).

Results

There were 30 patients who met our inclusion criteria: 10 males (66.7%) and 20 females (66.7%). Of these patients, 26 (86.7%) had a complete cleft lip and 4 (13.3%) had an incomplete cleft lip. The patients' average age at time of surgery was 16.2 years with a mean follow-up of 17.9 months. Subjective scores in both nasal and overall UCL SOE ratings improved from T0 to T1, 0.7 to 1.2 (P ≤ 0.001) and 3.6 to 4.7 (P ≤ 0.001), respectively. Visual analog scores in nasal and overall UCL SOE ratings improved between T0 and T2, 0.7 to 0.9 (P = 0.023) and 3.6 to 4.8 (P = 0.002), respectively. Of all the objective measures, nasal sill ratio and cleft height to width ratio correlated with improved subjective ratings across multiple time points.

Conclusions

Our study shows that objective measures such as nasal sill and nostril shape (cleft height to width ratio) correlate with improved subjective visual analog scale using the UCL SOE. The nasal sill is an often overlooked, yet essential, part of creating an aesthetically pleasing nose during cleft rhinoplasty.
Prelamination of the Radial Forearm Free Flap Using Free Full-Thickness Eyelid Skin Grafts
Authors: Jehn Philipp , Gellrich Nils-Claudius , Moysich Holger , Zeller Alexander-Nicolai , Lentge Fritjof , Tavassol Frank , Spalthoff Simon , Korn Philippe
Published: March 2022

Free flap transfer for reconstruction of intraoral defects is a common procedure in oral and maxillofacial surgery. For tumor-related defects, the radial forearm flap is widely used for soft tissue restoration. However, transfer of free skin grafts to the donor site region is often required for wound closure after free flap harvesting, resulting in esthetic disturbances due to shrinkage of the grafted skin, attendant scarring, or mismatches in skin texture or color. Furthermore, free flap transfer may result in hair follicle transfer into the oral cavity, causing unfavorable intraoral hair growth in adult men in particular. Free flap prelamination can help reduce the potential disadvantages of free flaps, in terms of both flap design and size and donor site morbidity. For surgical treatment of oral cancer in middle-aged and elderly patients, eyelid dermatochalasis may present as a comorbidity leading to esthetic impairments or, in cases involving the upper eyelid, even a reduced field of view. In these cases, bilateral blepharoplasty can reduce the excess eyelid skin. The present study is the first to attempt to use excised skin after bilateral blepharoplasty as full-thickness skin grafts for radial forearm free flap prelamination. This approach combined surgical therapy of eyelid dermatochalasis with free flap prelamination, thereby avoiding the need to harvest free skin grafts from other anatomically healthy regions to close the donor site defect and preventing the accompanying disadvantages. The reconstruction results and clinical outcomes of patients revealed that radial forearm free flap prelamination using bilateral free full-thickness eyelid skin grafts was an easy and feasible method for intraoral defect reconstruction. In particular, this approach could avoid intraoral hair growth and additional skin grafting from other healthy anatomical regions, yielding good esthetic and functional results at the flap's recipient and donor sites.
The Role of Maximal Locoregional Block in Autologous Breast Reconstruction
Authors: Atwez Abdelaziz , Martinez Carlos , Mujadzic Tarik , Mujadzic Mirsad , Chen Elliott , Friedman Harold I. , Gilstrap Jarom
Published: March 2022

Background

Enhanced Recovery After Surgery (ERAS) has become the standard of care in microsurgical breast reconstruction. The current literature provides overwhelming evidence of the benefit of ERAS pathways in improving quality of recovery, decreasing length of hospital stay, and minimizing the amount of postoperative narcotic use in these patients. However, there are limited data on the role of using maximal locoregional anesthetic blocks targeting both the abdomen and chest as an integral part of an ERAS protocol in abdominally based autologous breast reconstruction. The aim of this study is to compare the outcomes of implementing a comprehensive ERAS protocol with and without maximal locoregional nerve blocks to determine any added benefit of these blocks to the standard ERAS pathway.

Methods

Forty consecutive patients who underwent abdominally based autologous breast reconstruction in the period between July 2017 and February 2020 were included in this retrospective institutional review board–approved study. The goal was to compare patients who received combined abdominal and thoracic wall locoregional blocks as part of their ERAS pathway (study group) with those who had only transversus abdominis plane blocks. The primary end points were total hospital length of stay, overall opioids consumption, and overall postoperative complications.

Results

The use of supplemental thoracic wall block resulted in a shorter hospital length of stay in the study group of 3.2 days compared with 4.2 days for the control group (P < 0.01). Postoperative total morphine equivalent consumption was lower at 38 mg in the study group compared with 51 mg in the control group (P < 0.01). Complications occurred in 6 cases (15%) in the control group versus one minor complication in the thoracic block group. There was no difference between the 2 groups in demographics, comorbidities, and type of reconstruction.

Conclusion

The maximal locoregional nerve block including a complete chest wall block confers added benefits to the standard ERAS protocol in microvascular breast reconstruction.
Precise Intraoral Condylectomy With the Guide of Three-Dimensional Printed Template in a Mandibular Condylar Hyperplasia Patient
Authors: Yuan Hao , Jiang Tengfei , Shi Jun , Shen Steve G. F.
Published: March 2022

Purpose:

This study aimed to introduce an innovative method for mandibular condylectomy. A customized three-dimensional (3D) printed template is used to perform precise condylectomy in an intraoral approach.

Methods:

Condylectomy combined with orthognathic surgery was used for the treatment of facial asymmetry secondary to unilateral condylar hyperplasia. The customized 3D printed osteotomy guide was placed with an intraoral approach under endoscopy, in order to perform a precise condylectomy.

Result:

With the customized 3D printed template, the condylectomy was performed more precisely, and the conventional extraoral incision was avoided. The osteotomy line was accurately transferred from the virtual surgical plan to the real surgery, which assured the precise resection.

Conclusions:

The intraoral approach combined with a 3D printed template provides a novel solution to perform the condylectomy precisely.
Does Presurgical Nasoalveolar Molding Reduce the Need for Future Bone Grafting in Cleft Lip and Palate Patients? A Systematic Review and Meta-Analysis
Authors: Jahanbin Arezoo , Alizadeh Farzaneh Lal , Bardideh Erfan , Sharifi Sajjad , Nazari Mohammad Sadegh
Published: March 2022

Objective:

Nasoalveolar molding (NAM) is a technique that is utilized in patients with cleft lip/palate before performing lip surgery. This procedure has been shown to result in a more aesthetic nose with lesser columellar deviation and reduced scaring. The aim of our study was to evaluate the long-term results of NAM and gingivoperiosteoplasty in patients with cleft lip and palate.

Methods and Materials:

An electronic search of databases (ie, PubMed, ISI Web of Science, EMBASE, Scopus, and Google Scholar) from inception to March 2021 was performed and after selecting the eligible studies, relevant data were collected using piloted extraction forms. The success rate of NAM and gingivoperiosteoplasty, and Bergland score were pooled using random-effects inverse variance meta-analysis.

Results:

Seven studies were included in this meta-analysis and systematic review. The pooled mean success rate of NAM with gingivoperiosteoplasty (GPP) based on the continuity of alveolar bone structure was 71% (95% confidence interval [CI] = 54–85). This means that in 71% of cases NAM + GPP treatment eliminated the need for future bone grafts. Also, no significant difference between the success rate (risk ratio = 1.00, 95% CI = 0.64–1.58) and mean Bergland score (mean difference = 0.64, 95% CI = −1.04 to 2.31) of NAM + GPP and skeletal bone graft was found.

Conclusions:

Nasoalveolar molding and gingivoperiosteoplasty was successful in 71% of cases treating patients with cleft lip and palate. This treatment is similar with the secondary alveolar bone graft in both the success rate and the alveolar height that it generates while being less invasive and with lower morbidity.
Posterior Mandibular Segmental Split Osteotomy: A Novel Technique for Edentulous Space Reconstruction in Patients With Skeletal Class III Malocclusion
Authors: Zhu Zihe , Ni Shilei , Sun Xiumei , Wu Guomin
Published: March 2022

This study presents an innovative surgery that successfully improved the facial profile and occlusal function of a patient with a skeletal Class III malocclusion and posterior hypodontia. The patient had chief complaints of missing teeth and a protrudedjaw. A novel 1-stage surgery referred to as posterior mandibular segmental split osteotomy combined with Le Fort i osteotomy and BSSRO was used because the patient wanted to save time and was worried about periodontal complications associated with other treatment methods. As a result, a satisfying facial profile and a Class I occlusion with a normal position of the posterior dentoalveolar segment of the mandible were achieved with no adverse effects. Thus, posterior mandibular segmental split osteotomy can be considered an effective treatment for skeletal Class III malocclusion with posterior hypodontia.
An Ideal Choice for Closure of Large Free Radial Forearm Flap Donor Site Using a Local Full-Thickness Skin Graft
Authors: Shimbo Keisuke , Osaki Takeo , Koshima Isao
Published: March 2022

The local full-thickness skin graft (FTSG) method based on the V–Y closure is reported to be the most convenient and reliable technique for free radial forearm flap (FRFF) donor site closure. The spindle-shaped FTSG was the most common local closure method in free osteofasciocutaneous fibula flaps but not FRFF reconstructions, despite being conveniently applicable to FRFF donor sites. The authors devised a spindle-shaped FTSG harvested from the ipsilateral radial forearm as a new concept in repairing the FRFF donor site. This procedure was performed on 4 patients and the average flap defect size was 5.0 × 8.3 cm (41.3 cm2). The spindle-shaped FTSG is more likely to adapt to longer FRFFs, while a V–Y closure is more likely to adapt to wider ones. It is desirable to use both FTSGs properly depending on the large FRFF shape.
Prediction of R Status in Resections for Pancreatic Cancer Using Simplified Radiological Criteria
Authors: Bolm Louisa , Pisuchpen Nisanard , Qadan Motaz , Kambadakone Avinash , Sondermann Stefan , Mueller Katharina , Petruch Natalie , May Katharina , Zelga Piotr , Nebbia Martina , Michelakos Theodoros , Baba Taisuke , Roldan Jorge , Harrison Jon M. , Honselmann Kim C. , Keck Tobias , Lillemoe Keith D. , Ferrone Cristina R. , Wellner Ulrich F. , Fernandez-del Castillo Carlos
Published: March 2022

Objective:

Predicting R status before surgery for pancreatic cancer (PDAC) patients with upfront surgery and neoadjuvant therapy.

Summary Background Data:

Negative surgical margins (R0) are a key predictor of long-term outcomes in PDAC.

Methods:

Patients undergoing pancreatic resection with curative intent for PDAC were identified. Using the CT scans from the time of diagnosis, the 2019 NCCN borderline resectability criteria were compared to novel criteria: presence of any alteration of the superior mesenteric-portal vein (SMPV) and perivascular stranding of the superior mesenteric artery (SMA). Accuracy of predicting R status was evaluated for both criteria. Patient baseline characteristics, surgical, histopathological parameters, and long-term overall survival (OS) after resection were evaluated.

Results:

A total of 593 patients undergoing pancreatic resections for PDAC between 2010 and 2018 were identified. Three hundred and twenty-five (54.8%) patients underwent upfront surgery, whereas 268 (45.2%) received neoadjuvant therapy. In upfront resected patients, positive SMA stranding was associated with 56% margin positive resection rates, whereas positive SMA stranding and SMPV alterations together showed a margin positive resection rate of 75%. In contrast to these criteria, the 2019 NCCN borderline criteria failed to predict margin status. In patients undergoing neoadjuvant therapy, only perivascular SMA stranding remained a predictor of margin positive resection, leading to a rate of 33% R+ resections. Perivascular SMA stranding was related to higher clinical T stage (P = 0.003) and clinical N stage (P = 0.043) as well as perineural invasion (P = 0.022). SMA stranding was associated with worse survival in both patients undergoing upfront surgery (36 vs 22 months, P = 0.002) and neoadjuvant therapy (47 vs 34 months, P = 0.050).

Conclusions:

The novel criteria were accurate predictors of R status in PDAC patients undergoing upfront resection. After neoadjuvant treatment, likelihood of positive resection margins is approximately halved, and only perivascular SMA stranding remained a predictive factor.
Discrimination Toward Women in Surgery
Authors: Ferrari Linda , Mari Valentina , Parini Sara , Capelli Giulia , Tacconi Giovanna , Chessa Antonella , De Santi Gabriella , Verdi Daunia , Frigerio Isabella , Scarpa Marco , Gumbs Andrew , Spolverato Gaya
Published: March 2022

Background:

Over the past twenty years explicit gender bias toward women in surgery has been replaced by more subtle barriers, which represent indirect forms of discrimination and prevents equality.

Objective:

The aim of our scoping review is to summarize the different forms of discrimination toward women in surgery.

Methods:

The database search consisted of original studies regarding discrimination toward female surgeons.

Results:

Of 3615 studies meeting research criteria, 63 were included. Of these articles, 11 (18%) were focused on gender-based discrimination, 14 (22%) on discrimination in authorship, research productivity, and research funding, 21 (33%) on discrimination in academic surgery, 7 (11%) on discrimination in surgical leadership positions and 10 (16%) on discrimination during conferences and in surgical societies. The majority (n = 53, 84%) of the included studies were conducted in the U.S.A. According to our analysis, female surgeons experience discrimination from male colleagues, healthcare workers, but also from patients and trainees. Possible solutions may include acknowledgment of the problem, increased education of diversity and integration for the younger generations, mentorship, coaching, and more active engagement by male and female partners to support women in the surgical field.

Conclusions:

Gender-based discrimination toward women in the field of surgery has evolved over the past twenty years, from an explicit to a more subtle attitude. A work-environment where diversity and flexibility are valued would allow female surgeons to better realize their full potential.
III. Magnetical Observations at Port, &c. A. 1824-25, comprehending observations on the diurnal variation and diurnal intensity of the horizontal needle; also on the dip of the magnetic needle at Woolwich, and at different, within the arctic circle.
Authors: Parry William Edward , Foster Henry
Published: March 2022

The daily variation of the horizontal needle was first observed in London by Mr. Graham, in the year 1722; but in consequence of its small amount, it has always been considered amongst the minor phenomena which the magnetic needle presents. Mr. Barlow , however, having explained a method of encreasing the amount of this daily change very considerably, in any latitude, this phenomenon began to assume a different character, and seemed to furnish a subject of highly interesting, if not of useful, enquiry.
Hydrogen peroxide, sodium dichloro-s-triazinetriones and quaternary alcohols significantly inactivate the dry-surface biofilms of Staphylococcus aureus and Pseudomonas aeruginosa more than quaternary ammoniums
Authors: Chaggar Gurpreet K. , Nkemngong Carine A. , Li Xiaobao , Teska Peter J. , Oliver Haley F.
Published: March 2022

Globally, healthcare-associated infections (HAI) are the most frequent adverse outcome in healthcare delivery. Although bacterial biofilms contribute significantly to the incidence of HAI, few studies have investigated the efficacy of common disinfectants against dry-surface biofilms (DSB). The objective of this study was to evaluate the bactericidal efficacy of seven Environmental Protection Agency (EPA)-registered liquid disinfectants against DSB of

Staphylococcus aureus

and

Pseudomonas aeruginosa

. We hypothesized that overall, there will be significant differences among the bactericidal efficacies of tested disinfectants by product type and active ingredient class. We also hypothesized that depending on the species, higher bactericidal efficacies against DSB will be exhibited after 24 h of dehydration compared to 72 h. Wet-surface biofilms of

S. aureus

and

P. aeruginosa

were grown following EPA-MLB-SOP-MB-19 and dehydrated for 24 and 72 h to establish DSB. Seven EPA-registered disinfectants were tested against dehydrated DSB following EPA-MLB-SOP-MB-20. Overall, quaternary ammonium plus alcohol, sodium dichloro-s-triazinetrione and hydrogen peroxide products were more efficacious against DSB than quaternary ammoniums for both tested species. While there was no significant difference in the log10 reductions between 24 and 72 h

S

.

aureus

biofilms, significantly higher log10 reductions were observed when products were challenged with 24 h

P

.

aeruginosa

DSB compared to 72 h

P

.

aeruginosa

DSB. Species type, active ingredient class and dry time significantly impact disinfectant efficacy against DSB of

S. aureus

or

P. aeruginosa

.
The relative impact of vaccination momentum on COVID-19 rates of death in the USA in 2020/2021. The forgotten role of population wellness
Authors: Keddis Victor
Published: March 2022

It is widely accepted that individual underlying health conditions contribute to morbidity and mortality associated with COVID-19; and by inference population wellness will also contribute to COVID-19 outcomes. In addition, over the last two years the predominant pharmaceutical public health response to COVID-19 has been vaccination momentum (i.e. mass and rapid inoculation campaigns).

This paper aims to compare vaccination momentum throughout 2021 and measures of population wellness to estimate the relative impact of each on deaths attributed to COVID-19 across the 50 States of America, plus Washington DC, during 2020 (i.e. the pre-vaccination period) and 2021 (i.e. the vaccination period).

Our analysis shows that: (a) COVID-19 rates of death in 2020 are more important, and statistically more significant, at predicting rates of death in 2021 than vaccination momentum during 2021; (b) vaccination momentum does not predict the magnitude of change in COVID-19 rates of death between 2020 and 2021; and (c) for several underlying heath and risk factors vaccination momentum is significantly less important than population wellness at predicting COVID-19 rates of death.

Of particular interest are our observations that exercise and fruit consumption are 10.1 times more significant at predicting COVID-19 deaths than vaccination momentum, obesity (BMI 30+) is 9.6 times more significant at predicting COVID-19 deaths than vaccination momentum, heart attacks are 4.37 times more significant at predicting COVID-19 deaths than vaccination momentum and smoking is 3.2 times more significant at predicting COVID-19 deaths than vaccination momentum.

If medical and health regulators are to deliver a quantum decrease in COVID-19 deaths they must move beyond the overwhelming focus on COVID-19 vaccination. They must have the courage to urge governments and private organisations to mandate greater exercise, weight loss, less junk food, and better nutrition. And a concerted effort at reducing chronic adverse health conditions.
Understanding frailty: probabilistic causality between components and their relationship with death through a Bayesian network and evidence propagation
Authors: Ramírez-Aldana Ricardo , Parra-Rodríguez Lorena , Gomez-Verjan Juan Carlos , Garcia-Peña Carmen , Gutierrez-Robledo Luis Miguel
Published: March 2022

Identifying relationships between components of an index helps to have a better understanding of the condition they define. The Frailty Index (FI) measures the global health of individuals and can be used to predict outcomes as mortality. Previously, we modelled the relationship between the FI components (deficits) and death through an undirected graphical model, analyzing their relevance from a social network analysis framework. Here, we model the FI components and death through an averaged Bayesian network obtained through a structural learning process and resampling, to understand how the FI components and death are causally related. We identified that the components are not similarly related between them and that deficits are related according to its type. Two deficits were the most relevant in terms of their connections and other two were directly associated with death. We also obtained the strength of the relationships to identify the most plausible, identifying clusters of deficits heavily related. Finally, we propagated evidence (assigned values to all deficits) and studied how FI components predict mortality, obtaining a correct assignation of almost 74%, whereas a sensitivity of 56%. As a classifier of death, the more number of deficits included for the evidence, the best performance; but the FI seems not to be very good to correctly classify death people.
Patient-specific forecasting of post-radiotherapy prostate-specific antigen kinetics enables early prediction of biochemical relapse
Authors: Lorenzo Guillermo , Muzio Nadia di , Deantoni Chiara Lucrezia , Cozzarini Cesare , Fodor Andrei , Briganti Alberto , Montorsi Francesco , Pérez-García Víctor M. , Gomez Hector , Reali Alessandro
Published: March 2022

The detection of prostate cancer recurrence after external beam radiotherapy relies on the measurement of a sustained rise of serum prostate-specific antigen (PSA). However, this biochemical relapse may take years to occur, thereby delaying the delivery of a secondary treatment to patients with recurring tumors. To address this issue, here we propose to use patient-specific forecasts of PSA dynamics to early predict biochemical relapse. Our forecasts are based on mechanistic models of prostate cancer response to external beam radio-therapy, which are fit to patient-specific PSA data collected during standard post-treatment monitoring. Our results show a remarkable performance of our models in recapitulating the observed changes in PSA and yielding short-term predictions over approximately one year (cohort median RMSE of 0.10 to 0.47 ng/mL and 0.13 to 1.41 ng/mL, respectively). Additionally, we identify three model-based biomarkers that enable an accurate identification of biochemical relapse (AUC > 0.80) significantly earlier than standard practice (p < 0.01).
Low cost and real-time surveillance of enteric infection and diarrhoeal disease using rapid diagnostic tests: A pilot study
Authors: Watson Samuel I. , Ul Alam Mohammed Atique , Rego Ryan T.T. , Lilford Richard J. , Barman Ashok Kumar , Alam Baharul , Faruque A.S.G. , Islam Md. Sirajul
Published: March 2022

Background

Real-time disease surveillance is an important component of infection control in at-risk populations. However, data on cases or from lab testing is often not available in many low-resource settings. Rapid diagnostic tests (RDT), including immunochromatographic assays, may provide a low cost, expedited source of infection data.

Methods

We conducted a pilot survey-based prevalence mapping study of enteric infection in Camp 24 of the camps for the forcibly displaced Rohingya population from Myanmar in Cox’s Bazar, Bangladesh. We randomly sampled the population and collected and tested stool from under-fives for eight pathogens using RDTs in January-March 2021 and September-October 2021. A Bayesian geospatial statistical model allowing for imperfect sensitivity and specificity of the tests was adapted.

Results

We collected and tested 396 and 181 stools in the two data collection rounds. Corrected prevalence estimates ranged from 0.5% (Norovirus) to 27.4% (Giardia). Prevalence of E.coli O157, Campylobacter, and Cryptosporidium were predicted to be higher in the high density area of the camp with relatively high probability (70-95%), while Adenovirus, Norovirus, and Rotavirus were lower in the areas with high water chlorination. Clustering of cases of Giardia and Shigella was also observed, although associated with relatively high uncertainty.

Conclusions

With an appropriate correction for diagnostic performance RDTs can be used to generate reliable prevalence estimates, maps, and well-calibrated uncertainty estimates at a significantly lower cost than lab-based studies, providing a useful approach for disease surveillance in these settings.
Demuxafy: Improvement in droplet assignment by integrating multiple single-cell demultiplexing and doublet detection methods
Authors: Neavin Drew , Senabouth Anne , Hang Lee Jimmy Tsz , Ripoll Aida ,   sc-eQTLGen Consortium, Franke Lude , Prabhakar Shyam , Ye Chun Jimmie , McCarthy Davis J. , Melé Marta , Hemberg Martin , Powell Joseph E.
Published: March 2022

Recent innovations in droplet-based single-cell RNA-sequencing (scRNA-seq) have provided the technology necessary to investigate biological questions at cellular resolution. With the ability to assay thousands of cells in a single capture, pooling cells from multiple individuals has become a common strategy. Droplets can subsequently be assigned to a specific individual by leveraging their inherent genetic differences, and numerous computational methods have been developed to address this problem. However, another challenge implicit with droplet-based scRNA-seq is the occurrence of doublets - droplets containing two or more cells. The inaccurate assignment of cells to individuals or failure to remove doublets contribute unwanted noise to the data and result in erroneous scientific conclusions. Therefore, it is essential to assign cells to individuals and remove doublets accurately. We present a new framework to improve individual singlet classification and doublet removal through a multi-method intersectional approach.

We developed a framework to evaluate the enhancement in donor assignment and doublet removal through the consensus intersection of multiple demultiplexing and doublet detecting methods. The accuracy was assessed using scRNA-seq data of ∼1.4 million peripheral blood mononucleated cells from 1,034 unrelated individuals and ∼90,000 fibroblast cells from 81 unrelated individuals. We show that our approach significantly improves droplet assignment by separating singlets from doublets and classifying the correct individual compared to any single method. We show that the best combination of techniques varies under different biological and experimental conditions, and we present a framework to optimise cell assignment for a given experiment. We offer Demuxafy (https://demultiplexing-doublet-detecting-docs.readthedocs.io/en/latest/index.html) - a framework built-in Singularity to provide clear, consistent documentation of each method and additional tools to simplify and improve demultiplexing and doublet removal. Our results indicate that leveraging multiple demultiplexing and doublet detecting methods improves accuracy and, consequently, downstream analyses in multiplexed scRNA-seq experiments.
The impact of SNP density on quantitative genetic analyses of body size traits in a wild population of Soay sheep
Authors: James Caelinn , Pemberton Josephine M. , Navarro Pau , Knott Sara
Published: March 2022

Understanding the genetic architecture underpinning quantitative traits in wild populations is pivotal to understanding the processes behind trait evolution. The ‘animal model’ is a popular method for estimating quantitative genetic parameters such as heritability and genetic correlation and involves fitting an estimate of relatedness between individuals in the study population. Genotypes at genome-wide markers can be used to estimate relatedness; however, relatedness estimates vary with marker density, potentially affecting results. Increasing density of markers is also expected to increase the power to detect quantitative trait loci (QTL). In order to understand how the density of genetic markers affects the results of quantitative genetic analyses, we estimated heritability and performed genome-wide association studies (GWAS) on five body size traits in an unmanaged population of Soay sheep using two different SNP densities: a dataset of 37,037 genotyped SNPs, and an imputed dataset of 417,373 SNPs. Heritability estimates did not differ between the two SNP densities, but the high-density imputed SNP dataset revealed four new SNP-trait associations that were not found with the lower density dataset, as well as confirming all previously-found QTL. We also demonstrated that fitting fixed and random effects in the same step as performing GWAS is a more powerful approach than pre-correcting for covariates in a separate model.
Emergence of integrated information at macro timescales in real neural recordings
Authors: Leung A , Tsuchiya N
Published: March 2022

How a system generates conscious experience remains an elusive question. One approach towards answering this is to consider the information available in the system from the perspective of the system itself. Integrated information theory (IIT) proposes a measure to capture this, integrated information (Φ). While Φ can be computed at any spatiotemporal scale, IIT posits that it be applied at the scale at which the measure is maximised. Importantly, Φ should emerge to be maximal not at the smallest spatiotemporal scale, but at some macro scale where system elements or timesteps are grouped into larger elements or timesteps. Emergence in this sense has been demonstrated in artificial binary systems, but it remains unclear whether it occurs in real neural recordings which are generally continuous and noisy. Here we first utilise a computational model to confirm that Φ becomes maximal at the temporal scales underlying its generative mechanisms. Second, we search for emergence in local field potentials from the fly brain recorded during wakefulness and anaesthesia, finding that normalised Φ (wake/anaesthesia), but not raw Φ values, peaks at 5 ms. Lastly, we extend our model to investigate why raw Φ values themselves did not peak. This work extends the application of Φ to simple artificial systems consisting of logic gates towards searching for emergence of a macro spatiotemporal scale in real neural systems.