bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrin β5 enhances the malignancy of human colorectal cancer by increasing the TGF-β signaling
Authors: Shi Wei , He Jie , Huang Yuee , Zeng Zheng , Feng Zhiqiang , Xu Haoming , Nie Yuqiang
Published: February 2021

Increased integrin β5 (ITGB5) expression is associated with the progression and metastasis of several types of cancers. However, whether upregulated ITGB5 expression can act as a prognostic factor for colorectal cancer (CRC) remains controversial. In this study, we aimed to identify the role ITGB5 plays during the pathogenesis of human CRC and explore the underlying molecular mechanism. Here, we show that ITGB5 expression is upregulated in CRC and is significantly associated with exacerbated CRC malignancy and an unfavourable overall survival rate among CRC patients. ITGB5 silencing significantly inhibited the proliferation and invasion of human CRC cell lines (HCT116 and HT29) in vitro and suppressed the growth and metastasis of implanted CRC tumours in vivo. Mechanistically, upregulated ITGB5 expression enhanced transforming growth factor β/Smad signalling and facilitated the epithelial–mesenchymal transition in CRC cells. Together, such findings indicate that ITGB5 acts as an oncogenic factor to enhance the malignancy of CRC and suggest that ITGB5 may be a therapeutic target.
Fetal Vesicoallantoic Cyst and Intraabdominal Defects: An Unusual Case and Review of the Literature
Authors: Delvaux Mathieu , Sznajer Yves , Marbaix Etienne , Biard Jean Marc , Hubinont Corinne
Published: February 2021

We present an unusual and, until now, unreported case of vesicoallantoic cyst associated with multiple malformations in a fetus. A differential diagnosis is discussed, including the hypothesis of a genetic disorder.
Genetics of hypertriglyceridemia and atherosclerosis
Authors: Gill Praneet K. , Dron Jacqueline S. , Hegele Robert A.
Published: February 2021

Purpose of review

The relationship between elevated triglyceride levels (i.e. hypertriglyceridemia) and risk of atherosclerotic cardiovascular disease (ASCVD) has been investigated for decades. Recent genetic studies have sought to resolve the decades-old question of a causal relationship.

Recent findings

Genetic studies seem to demonstrate associations between elevated triglyceride levels and ASCVD risk. Mendelian randomization studies suggest this association may be causal. However, simultaneous pleiotropic effects of metabolically linked lipid variables – such as non-HDL cholesterol, apolipoprotein B and HDL cholesterol -- often go unaccounted for in these studies. Complex underlying pleiotropic interactions of triglycerides with these lipid fractions together with unmeasured intercalated nonlipid-related mechanisms, such as inflammation and coagulation, impair the ability of genetic studies to implicate a direct role for triglycerides on ASCVD risk. One potential mechanism seems largely driven by the cholesterol carried within triglyceride-rich lipoproteins and their remnants, rather than their triglyceride content.

Although the exact mechanisms linking elevated triglyceride levels to ASCVD remain to be determined, new therapeutics that reduce triglyceride levels might be advantageous in certain patients. Newer investigational triglyceride-lowering therapies derived from human genetics target key proteins, such as apo C-III and ANGPTL3. Although these treatments clearly lower triglyceride levels, their efficacy in atherosclerotic risk reduction remains unproven.
OnabotulinumtoxinA affects cortical recovery period but not occurrence or propagation of cortical spreading depression in rats with compromised blood–brain barrier
Authors: Melo-Carrillo Agustin , Strassman Andrew M. , Schain Aaron J. , Broide Ron S. , Cai Brian B. , Rhéaume Catherine , Brideau-Andersen Amy D. , Ashina Sait , Flores-Montanez Yadira , Brin Mitchell F. , Burstein Rami
Published: February 2021

OnabotulinumtoxinA (BoNT-A) is an Food and Drug Administration-approved, peripherally acting preventive migraine drug capable of inhibiting meningeal nociceptors. Expanding our view of how else this neurotoxin attenuates the activation of the meningeal nociceptors, we reasoned that if the stimulus that triggers the activation of the nociceptor is lessened, the magnitude and/or duration of the nociceptors' activation could diminish as well. In the current study, we further examine this possibility using electrocorticogram recording techniques, immunohistochemistry, and 2-photon microscopy. We report (1) that scalp (head) but not lumbar (back) injections of BoNT-A shorten the period of profound depression of spontaneous cortical activity that follows a pinprick-induced cortical spreading depression (CSD); (2) that neither scalp nor lumbar injections prevent the induction, occurrence, propagation, or spreading velocity of a single wave of CSD; (3) that cleaved SNAP25—one of the most convincing tools to determine the anatomical targeting of BoNT-A treatment—could easily be detected in pericranial muscles at the injection sites and in nerve fibers of the intracranial dura, but not within any cortical area affected by the CSD; (4) that the absence of cleaved SNAP25 within the cortex and pia is unrelated to whether the blood–brain barrier is intact or compromised; and (5) that BoNT-A does not alter vascular responses to CSD. To the best of our knowledge, this is the first report of peripherally applied BoNT-A's ability to alter a neuronal function along a central nervous system pathway involved in the pathophysiology of migraine.
European Whites May Need Lower Minimum Therapeutic Clozapine Doses Than Those Customarily Proposed
Authors: Schoretsanitis Georgios , Smith Robert L. , Molden Espen , Solismaa Anssi , Seppälä Niko , Kopeček Miloslav , Švancer Patrik , Olmos Ismael , Vázquez Marta , Iglesias-Garcia Celso , Iglesias-Alonso Ana , Spina Edoardo , de Leon Jose
Published: February 2021

Purpose/Background

A nomogram from a British naturalistic study proposed that the clozapine dosing needed to reach a serum concentration of 350 ng/mL ranged from 265 mg/d (female nonsmokers) to 525 mg/d (male smokers). Some European reviews have used these dosing recommendations, which seem greater than what we found in an Italian White sample ranging from 245 mg/d (female nonsmokers) to 299 mg/d (male smokers). Five other published samples of European Whites were added to the Italian sample to estimate clozapine doses recommended for reaching 350 ng/mL.

Methods/Procedures

Average clozapine metabolizers were obtained by eliminating outliers with confounding variables: (1) psychiatric inducers and inhibitors; (2) doses less than 100 mg/d; and (3) when possible, patients with inflammation, obesity, or using oral contraceptives. The study included 1363 average metabolizer European Whites: the Italian sample and 5 new samples. Mean averages that reached serum concentration levels of 350 ng/mL were calculated after stratification by sex and smoking status in each sample. Then, weighted mean averages were obtained by combining the 6 samples.

Findings/Results

The estimated weighted mean clozapine dosages ranged from 236 to 368 mg/d (236 mg/d in 218 female nonsmokers, 256 mg/d in 340 male nonsmokers, 357 mg/d in 269 female smokers, and 368 mg/d in 546 male smokers).

Implications/Conclusions

Our recommended dosages are less than those recommended in Europe. Future studies in European Whites need to replicate these recommended doses for average metabolizer patients after sex and smoking stratification and further explore clozapine dosing for those with relevant clinical confounders.
Identification of two novel mutations in three children with congenital factor VII deficiency
Authors: Liang Kairong , Nikuze Lauriane , Zhang Fuyong , Lu Zhengjing , Wei Manlv , Wei Hongying
Published: February 2021

Congenital factor VII deficiency (FVIID) is a rare F7 gene mutation causing bleeding disorder inherited in an autosomal recessive manner. In this study, we aimed to identify genetic defects and analyze their relationships with phenotype in three Chinese FVIID patients. The diagnosis of FVIID was made based on FVII coagulant activity (FVII:C) levels assessed through prothrombin time assay. Direct sequencing and protein modeling were performed to detect genetic mutations and the resulting protein expression. Patient 1, a 2-year-old girl, presented with mild bleeding and was found to have a FVII:C of 0.2% and a compound heterozygous F7 Cys389Gly/Cys115Arg mutation. Patient 2, a 7-year-old boy, consulted for moderate bleeding and was found to have a FVII:C of 0.8% and a compound heterozygous F7 Thr241Asn/Pro324Leu mutation. Patient 3, a 5-year-old boy who developed a mild bleeding after trauma was found to have a FVII:C of 1.8% and a compound heterozygous F7 Thr241Asn/ IVS5-2A>G mutation. We hereby report three congenital FVIID patients with FVII:C less than 2% and their respective F7 mutations, two of which (F7 Cys115Arg, Pro324Leu) are novel. The molecular model analysis of the two novel mutations F7 Cys115Arg and Pro324Leu respectively indicated impairment of the proper folding of epidermal growth factor 1 domain situated on F7 gene and impairment of the procoagulant function of FVII both leading to the congenital deficiency of FVII.
Markers of Bile Acid Metabolism in Pediatric Diarrhea Predominant Irritable Bowel Syndrome and Healthy Controls
Authors: Beinvogl Beate C. , Manini Mhd Louai , Camilleri Michael , Donato Leslie J. , Harmsen William Scott , Absah Imad , Burch Elizabeth , Schechter Neil L. , Nurko Samuel
Published: February 2021

Objectives:

Excessive fecal bile acids in adults have been associated with diarrhea‐predominant irritable bowel syndrome (IBS‐D), but their role in pediatric IBS‐D is unknown. Serum markers including 7α‐hydroxy‐4‐cholesten‐3‐one (C4) and fibroblast growth factor‐19 (FGF‐19) were validated in adults to detect bile acid diarrhea (BAD) compared to 48‐hour fecal bile acid collection (48FBA). Our aims were to assess fasting serum C4 and FGF–19 and 48FBA in a pediatric population, to compare measurements in IBS‐D patients and healthy controls (HC), and to determine the prevalence of BAD among children with IBS‐D.

Methods:

Using a cross‐sectional design, 26 patients with IBS‐D and 56 HC were recruited in two pediatric tertiary care centers. Fasting serum C4 and FGF‐19 and 48FBA were obtained. Participants completed a 7‐day bowel diary coinciding with stool collection. Associations were analyzed using Spearman correlations.

Results:

Mean age was 14.7 ± 2.5 years (42.3% female) in IBS‐D and 12.6 ± 2.4 years (39.3% female) in HC. There was a significant correlation of C4 with 48FBA (r = 0.48, P < 0.05) and an inverse association with FGF‐19 (r = –0.43, P < 0.05). No significant differences were noted in C4 (P = 0.32), FGF‐19 (P = 0.1), or 48FBA (P = 0.5) between IBS‐D and HC groups; however, 20% of IBS‐D patients had elevated C4 and 28% had low FGF‐19 values.

Fecal primary BA was significantly correlated with stool frequency (r = 0.45, P < 0.002).

Conclusions:

Correlations of C4 with 48FBA and FGF‐19 are confirmed in a pediatric population. Twenty percent of pediatric patients with IBS‐D had abnormal fasting serum C4. This serum test could be applied to identify BAD in pediatric IBS‐D.
A Diet High in Fat and Fructose Induces Early Hepatic Mitochondrial Aging
Authors: Bramlage Kristin S. , Bhattacharjee Jashdeep , Kirby Michelle , Myronovych Andriy , Gupta Rohun , Gonzalez Rosa‐Maria Salazar , Xanthakos Stavra , Bove Kevin , Kohli Rohit
Published: February 2021

To investigate the effect of high fructose diet on ultrastructure and content of hepatic mitochondria, we randomized 6–8 weeks old male C57Bl6/J mice to ad lib chow or high‐fat‐high‐fructose (HF2) diet for 32 weeks. HF2‐fed mice gained more weight, had higher plasma alanine aminotransferase, and fasting glucose levels and increased hepatic triglyceride content at all time points compared to chow‐fed mice. HF2‐fed mice had lower mitochondrial to nuclear DNA ratio compared to chow‐fed mice. HF2‐fed mice had lower average mitochondrial surface area and the number of mitochondria compared to chow‐fed mice. HF2‐fed mice had higher expression of the hepatic endoplasmic reticulum stress marker Chop, compared to chow‐fed mice. A diet high in fat and fructose leads to enhanced hepatic mitochondrial aging, depletion, and dysfunction, which may be important determinants of nonalcoholic steatohepatitis pathogenesis.
Pediatric‐onset Inflammatory Bowel Disease Has Only a Modest Effect on Final Growth
Authors: Assa Amit , Assayag Noa , Balicer Ran D. , Gabay Hagit , Greenfeld Shira , Kariv Revital , Ledderman Natan , Matz Eran , Dotan Iris , Ledder Oren , Yerushalmy‐Feler Anat , Turner Dan , Cohen Shlomi
Published: February 2021

Objectives:

The impact of pediatric‐onset inflammatory bowel disease (IBD) on growth is debated. We aimed to investigate the effect of IBD on anthropometric measures at young adulthood.

Methods:

Children diagnosed with Crohn disease (CD) or ulcerative colitis (UC) (2005–2019) were identified in a national database along with matched non‐IBD controls.

Results:

Overall, 2229 IBD cases (68% CD) were matched to 4338 controls. Only females with CD differed in final height from controls (z scores: −0.37 ± 1.09 vs −0.25 ± 1.06, respectively; P = 0.01), corresponding to a mean difference of 0.7 ± 0.2 cm (all females) and 1.2 ± 0.3 cm in females diagnosed <14 years (P = 0.02). Final height was reduced in both sexes according to adjusted mean height difference analysis (−0.43 cm, 95% confidence interval −0.85 to −0.02; P = 0.04). This difference increased in patients with CD who underwent abdominal surgery (−0.91 cm, 95% confidence interval −1.39 to −0.42; P = 0.01). The proportion of patients with CD achieving final height z scores of −1 and zero differed significantly from controls for both males (71.1% and 34.8% vs 79.1% and 43.0%, respectively; P < 0.001) and females (67.7% and 30.4% vs 79.6%, and 43.3%, respectively; P < 0.001). Patients treated with anti‐tumor necrosis factor agents during growth potential had similar height improvement to other regimens. Predominantly, patients with CD were leaner, with a greater proportion of subjects with underweight, compared with controls.

Conclusions:

In pediatric‐onset IBD, absolute final height was modestly affected by females with CD. Nevertheless, greater proportions of both sexes with early diagnosis of CD failed to achieve normal final height, compared with controls.
The Effect of Nutritional Therapy on Bone Mineral Density and Bone Metabolism in Pediatric Crohn Disease
Authors: Lev‐Tzion Raffi , Ben‐Moshe Tehila , Abitbol Guila , Ledder Oren , Peleg Sarit , Millman Peri , Shaoul Ron , Kori Michal , Assa Amit , Cohen Shlomi , Strich David , Revel‐Vilk Shoshana , Tiomkin Maayan , Levine Arie , Sigall Boneh Rotem , Turner Dan
Published: February 2021

Objectives:

Both the inflammatory burden of Crohn disease (CD) and corticosteroids have a negative effect on bone density. Exclusive enteral nutrition (EEN) avoids corticosteroids and promotes endoscopic healing. We aimed to explore the effect of nutritional therapy on bone health in pediatric CD.

Methods:

This was a planned sub‐study of a clinical trial enrolling children with new‐onset mild‐moderate CD. Children were randomized to either 6 weeks EEN followed by 6 weeks 25% partial enteral nutrition (PEN) or 6 weeks of 50% PEN with a CD exclusion diet followed by 6 weeks of 25% PEN with exclusion diet. Bone formation and resorption were measured at baseline, week 12 and week 24 by serum C‐Propeptide of Type I Procollagen (CICP) and type I Collagen N‐Telopeptide (NTX), respectively. Bone mineral density (BMD) was measured by dual energy X‐ray absorptiometry (DXA) scan at baseline and week 24.

Results:

Median CICP improved from 130 ng/mL (106–189) at baseline to 223 (143–258) at week 12 and 193 (143–252) at week 24 (P = 0.016 for both, n = 29 children). Median NTX remained unchanged (P = 0.45 and P = 0.45). Thirty‐six children had DXA scans performed at diagnosis; 81% and 33% had z scores of <−1 and <−2, respectively. DXA z scores did not improve from baseline (adjusted total body less head [TBLH] BMD −1.62 ± 0.87) to week 24 (−1.76 ± 0.75; P = 0.30, n = 21 with both scans).

Conclusions:

Low bone density is common in new‐onset mild‐moderate pediatric CD. CICP, a sensitive marker of bone formation, improved following dietary intervention but this was not associated with improved BMD.
Identifying Language Features Associated With Needs of Ovarian Cancer Patients and Caregivers Using Social Media
Authors: Lee Young Ji , Jang Hyeju , Campbell Grace , Carenini Giuseppe , Thomas Teresa , Donovan Heidi
Published: February 2021

Background

Online health communities (OHCs) can be a source for clinicians to learn the needs of cancer patients and caregivers. Ovarian cancer (OvCa) patients and caregivers deal with a wide range of unmet needs, many of which are expressed in OHCs. An automated need classification model could help clinicians more easily understand and prioritize information available in the OHCs.

Objective

The aim of this study was to use initial OHC postings to develop an automated model for the classification of OvCa patient and caregiver needs.

Methods

We collected data from the OvCa OHC and analyzed the initial postings of patients and caregivers (n = 853). Two annotators coded each posting with 12 types of needs. Then, we applied the machine learning approach with bag-of-words features to build a model to classify needs. F1 score, an indicator of model accuracy, was used to evaluate the model.

Results

The most reported needs were information, social, psychological/emotional, and physical. Thirty-nine percent of postings described information and social needs in the same posting. Our model reported a high level of accuracy for classifying those top needs. Psychological terms were important for classifying psychological/emotional and social needs. Medical terms were important for physical and information needs.

Conclusions

We demonstrate the potential of using OHCs to supplement traditional needs assessment. Further research would incorporate additional information (eg, trajectory, stage) for more sophisticated models.

Implications for Practice

This study shows the potential of automated classification to leverage OHCs for needs assessment. Our approach can be applied to different types of cancer and enhanced by using domain-specific information.
Infections in Children With Cancer
Authors: Karavanaki Kyriaki , Kossiva Lydia , Sklavou Rigina , Kakleas Kostas , Tsentidis Charalambos , Gourgiotis Dimitris , Marmarinos Antonis , Sdogou Triantafyllia , Tsolia Maria , Polychronopoulou Sophia
Published: February 2021

Background

Infections in patients with cancer are a major cause of morbidity and mortality. In most cases, the presence of neutropenia renders them prone to infections to either common or opportunistic pathogens. A wide spectrum of bacterial, viral, or fungal agents is encountered in these patients.

Aim

The aim of this study was to evaluate infection types and pathogens in pediatric patients with cancer with and without neutropenia.

Methods

A total of 37 pediatric patients with cancer (median age ± 25% quartile, 6.0 ± 2.0% years) with 70 febrile episodes were evaluated at fever’s onset and 48 hours later with complete blood count, C-reactive protein, cultures of biological fluids, polymerase chain reaction, and antibody titers.

Results

Of 70 infections, 30 (42.85%) were bacterial, 13 (18.57%) were viral, 3 (4.28%) were fungal, 16 (22.85%) were fever of unknown origin, 18 (25.71%) were opportunistic, and 12 (17.14%) were mixed infections. Neutropenia was detected in 42 (60.0%) of 70 febrile episodes, mainly in patients with hematological malignancies [odds ratio, 2.81 (0.96–8.22); P = 0.059]. Neutropenic patients had higher prevalence of mucocutaneous infections (47.6% vs 7.14%; P = 0.004). Herpes simplex virus 1 infections occurred only in the neutropenic group (14.3%).

Conclusions

Patients with cancer exhibited a high prevalence of bacterial (42.85%), opportunistic (25.7%), and mixed infections (17.14%). Patients with hematological malignancies and neutropenia presented higher frequency of mucocutaneous and herpes simplex virus 1 infections than the nonneutropenic ones.
Osteomyelitis in an Unusual Location With an Atypical Presentation
Authors: Gerber Nicole , Fawcett Kelsey , Bittman Mark , Beiner Joshua
Published: February 2021

Bacterial osteomyelitis of the scapula is rare in pediatric patients. When it occurs, it usually affects young infants and patients often exhibit fever and functional limitation of the extremity. We present a case of a 12-year-old boy with subacute bacterial scapular osteomyelitis and a normal physical examination. The patient was briefly treated with intravenous antibiotics and then transitioned to oral antibiotics to complete a 4-week course for methicillin-sensitive Staphylococcus aureus osteomyelitis.
Improving CPR Quality by Using a Real-Time Feedback Defibrillator During Pediatric Simulation Training
Authors: Frazier Maria , Dewan Maya , Keller-Smith Rachel , Shoemaker Jamie , Stewart Claire , Tegtmeyer Ken
Published: February 2021

Objective

The aim of this study was to assess the effectiveness of a defibrillator with real-time feedback during code team training to improve adherence to the American Heart Association (AHA) resuscitation guidelines.

Methods

This is a retrospective cohort study designed to compare pediatric resident adherence to the AHA cardiopulmonary resuscitation guidelines before and after use of real-time feedback defibrillator during code team training simulation. After institution of a real-time feedback defibrillator, first-year resident's adherence to the AHA guidelines for chest compression rate (CCR), fraction, and depth during code team training from January 2017 to December 2018 was analyzed. It was then compared with results of a previously published study from our institution that analyzed the CCR and fraction from January 2015 to January 2016, before the implementation of a defibrillator with real-time feedback.

Results

We compared 19 eligible session preintervention and 36 postintervention sessions. Chest compression rate and chest compression fraction (CCF) were assessed preintervention and postintervention. The depth of compression was only available postintervention. There was improvement in the proportion of code team training sessions with mean compression rate (74% preintervention vs 100% postintervention, P = 0.003) and mean CCF (79% vs 97%, P = 0.04) in adherence with the AHA guideline.

Conclusions

The use of real-time feedback defibrillators improved the adherence to the AHA cardiopulmonary resuscitation guidelines for CCF and CCR during pediatric resident simulation.
Malignant Peritoneal Mesothelioma Associated With Endometriosis: A Clinicopathologic Study of 15 Cases
Authors: Malpica Anais , Euscher Elizabeth D. , Marques-Piubelli Mario L. , Miranda Roberto N. , Fournier Keith F. , Raghav Kanwal P. , Ramalingam Preetha
Published: February 2021

Only a few cases of malignant peritoneal mesothelioma (MPeM) associated with endometriosis have been published; with chronic inflammation of the peritoneum associated with the latter being postulated as an inducing factor in the pathogenesis of this tumor. We assessed the clinicopathologic characteristics of MPeM associated with endometriosis to determine if there were other factors besides inflammation that may contribute to the pathogenesis in this patient population. Fifteen MPeM associated with endometriosis were retrieved from our files. Most presented with abdominal/pelvic pain, mass or distention; median age was 45 yr. Only 16% of patients had a history of asbestos exposure. In contrast, a third of the patients had a personal history of other neoplasms, and >80% had a family history of malignancies. Although most tumors had gross and microscopic features typical of MPeM, some had confounding features including “adhesion-like” appearance or gelatinous cysts/nodules, and signet ring cells. Tumors were epithelioid (9) and biphasic (6). MPeM was misdiagnosed as Müllerian carcinoma in 40% of cases. All patients (n=15) had cytoreductive surgery in addition to other therapies. Only 2/12 patients died of disease (17%). The 3- and 5-yr overall survival was 90%. MPeM associated with endometriosis tends to occur in patients with personal/familial history of malignancies, which may be a predisposing factor. In light of this finding, the role of endometriosis in the pathogenesis of MPeM is likely less relevant. The favorable outcome seen in these patients may be related to germline mutations or the hormonal milieu and needs further investigation.
Reducing Alarm Burden in a Level IV Neonatal Intensive Care Unit
Authors: McCauley Kortany E. , Schroeder Alissa A. , DeBoth Tawney K. , Wiebe Alexander M. , Bosley Christopher L. , Ballweg Diane D. , Fang Jennifer L.
Published: February 2021

Introduction:

Excessive alarm burden contributes to alarm fatigue, causing staff to ignore or delay response to clinically significant alarms. The objective of this quality improvement project was to reduce yellow self-resolving SpO2 alarms from a mean of 14 alarms/patient-hour (APH) to 7 APH (a 50% reduction) within a 6-month period, without significantly decreasing the amount of time spent in target SpO2 range (90%–95%).

Methods:

A multidisciplinary team used Define-Measure-Analyze-Improve-Control methodology to identify etiologies of alarm frequency and design improvement interventions to reduce alarm burden in a single-site Level IV NICU. Data-driven changes in alarm limit settings, alarm delay, and trial of a new pulse oximeter probe were used. Alarm data from the bedside monitor were analyzed following each improvement cycle. As a balancing measure, histograms monitored time spent in target SpO2 range.

Results:

SpO2 alarm data were collected for 4,320 patient-hours (180 patient-days) on 40 neonatal intensive care unit patients meeting inclusion criteria. Corresponding histograms were obtained for each patient day. Following 5 Plan-Do-Study-Act cycles, the mean number of yellow self-resolving SpO2 alarms decreased from 14 to 5 APH, a 64% decrease. There was no difference in time spent in target SpO2 range (50% versus 50%, P = 0.93). After achieving the project aim, 2 control phase measurements demonstrated sustained improvement (mean APH = 6).

Conclusions:

Yellow self-resolving SpO2 alarm frequency was reduced by 64% through the implementation of data-driven changes in alarm limit settings, alarm delays, and trial of a more sensitive oximeter probe without introducing harm to patients.
Stewardship Intervention to Optimize Central Venous Catheter Utilization in Critically Ill Children
Authors: Blumenthal Jennifer A. , Ormsby Jennifer A. , Mirchandani Dimple , Petti Chonel A. , Carpenter Jane , Geller Maggie , Harding Stephanie N. , O’Brien Mary , Sandora Thomas J. , Kleinman Monica E. , Priebe Gregory P. , Mehta Nilesh M.
Published: February 2021

Introduction:

We aimed to describe utilization and indication(s) for long-term central venous catheters (CVCs) in a pediatric intensive care unit (PICU) and identify potential strategies to decrease CVC utilization.

Methods:

We conducted a single-center prospective quality improvement initiative at a 30-bed PICU in a large, freestanding, academic children’s hospital. We created an electronic report to identify patients with an indwelling CVC for 7 days and older (defined as long term). We discussed the ongoing need for each long-term CVC with PICU clinicians at weekly interdisciplinary structured “CVC stewardship rounds.” We then made recommendations around expedited removal of CVCs. We conducted multiple Plan-Do-Study-Act cycles to categorize CVC indications, identify modifiable factors, and educate PICU clinicians. We hypothesized that CVC stewardship rounds would decrease long-term CVC utilization in our PICU.

Results:

From October 2016 to September 2017, 607 long-term CVCs were eligible for the stewardship intervention. Compared to the preintervention period, we recorded a significant increase in peripherally inserted central catheters and a decrease in nontunneled CVCs (P < 0.001). Most patients had single- or double-lumen CVCs in both the preintervention and intervention periods (86% and 91%, respectively). The utilization of overall long-term CVC devices, and those with modifiable indications, decreased during the intervention period.

Conclusions:

A single-center QI intervention focused on PICU CVC stewardship was associated with a decrease in CVC utilization.
Patient Safety Education in Entry to Practice Pharmacy Programs: A Systematic Review
Authors: El-Awaisi Alla , Koummich Sarra , Koraysh Somaya , El Hajj Maguy Saffouh
Published: February 2021

Objectives

The aim of this systematic review was to synthesize, summarize, and evaluate the quality of extant quantitative and qualitative literature related to patient safety in pharmacy education. This systematic review included literature that targeted the content, delivery, and outcomes of patient safety in addition to literature that explored the perspectives of pharmacy students and faculty on how patient safety is integrated within their curricula.

Methods

A systematic review was conducted. Four electronic databases were searched for articles published between 2000 and 2019: PubMed, MEDLINE, EMBASE, and ScienceDirect. Selection was based on prespecified criteria and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Two independent reviewers selected articles, extracted data, and assessed articles’ qualities using the Crowe Critical Appraisal Tool. Discrepancies were resolved by consensus or by consulting a third reviewer. Descriptive synthesis of data was performed.

Results

Twenty-five eligible articles were included. The majority of studies originated from United States (n = 15). Educational content involved principles of patient safety, and identification, disclosure, and management of medication errors. There was a lack of standardization on how patient safety is incorporated into the pharmacy curricula. Eleven articles (64%) were interprofessional in nature, delivered as a patient safety course (n = 6), through simulation (n = 3), as seminars (n = 1), or as part of student experiential learning (n = 1). Of the 7 articles discussing delivery of patient safety through courses or modules, 4 (57%) were offered as elective courses. Students’ perceptions and attitudes significantly improved after all patient safety interventions, reflecting the importance of addressing patient safety in education to ensure optimum future practice.

Conclusions

This systematic review demonstrated how patient safety education was incorporated into pharmacy programs in terms of the content and methods of delivery. It was promising to see patient safety content being delivered interprofessionally and in experiential education. Students and faculty regarded implementing patient safety in education as an essential act to meet future work demands. Longitudinal studies to assess the long-term impact of incorporating patient safety on student behaviors upon graduation and health outcomes are needed.
Impact of Efavirenz Mid-dose Plasma Concentration on Long-Term Weight Change Among Virologically Suppressed People Living With HIV
Authors: Huang Sung-Hsi , Huang Wei-Chieh , Lin Shu-Wen , Chuang Yu-Chung , Sun Hsin-Yun , Chang Sui-Yuan , Kuo Po-Hsien , Wu Pei-Ying , Liu Wen-Chun , Chiang Chieh , Hung Chien-Ching , Chang Shan-Chwen
Published: February 2021

Background:

Pharmacogenetic studies have shown that slow and intermediate metabolizers of efavirenz (EFV) gained less weight compared with extensive metabolizers. It is hypothesized that increased EFV exposure suppresses weight gain. We investigated the effect of EFV mid-dose plasma concentration (C12) on long-term weight change among virologically suppressed people living with HIV (PLWH).

Methods:

Participants in a prospective EFV pharmacokinetic study were included if they had been taking EFV-containing combination antiretroviral therapy for more than 240 weeks and had 3 or more weight measurements. The weight changes and time to ≥5% of weight gain over 192 weeks were compared between PLWH with higher and those with lower EFV C12 (using mean population C12 as the cutoff). EFV C12 and CYP2B6 516G>T polymorphism were examined in generalized estimating equations and in a Cox proportional hazards model for associations with weight gain, after adjustments for age, sex, companion antiretroviral agent, CD4 lymphocyte count, and plasma HIV RNA.

Results:

One hundred eighteen PLWH were included. PLWH with higher EFV C12 had less mean weight gain compared with those with lower C12 after 192 weeks (−0.09 vs +1.58 kg, P = 0.033). PLWH with higher C12 were less likely to gain ≥5% weight in Kaplan–Meier analysis (P = 0.0003). In both generalized estimating equations and Cox proportional hazards models, a higher EFV C12 was associated with less weight gain, while CYP2B6 516G>T was not, after adjustments made for confounding factors.

Conclusions:

Our findings support that increased EFV exposure was associated with less weight gain.
Maternal HIV Infection and Spontaneous Versus Provider-Initiated Preterm Birth in an Urban Zambian Cohort
Authors: Price Joan T. , Vwalika Bellington , Edwards Jessie K. , Cole Stephen R. , Kasaro Margaret P. , Rittenhouse Katelyn J. , Kumwenda Andrew , Lubeya Mwansa K. , Stringer Jeffrey S. A.
Published: February 2021

Objective:

We investigated the effect of maternal HIV and its treatment on spontaneous and provider-initiated preterm birth (PTB) in an urban African cohort.

Methods:

The Zambian Preterm Birth Prevention Study enrolled pregnant women at their first antenatal visit in Lusaka. Participants underwent ultrasound, laboratory testing, and clinical phenotyping of delivery outcomes. Key exposures were maternal HIV serostatus and timing of antiretroviral therapy initiation. We defined the primary outcome, PTB, as delivery between 16 and 37 weeks' gestational age, and differentiated spontaneous from provider-initiated parturition.

Results:

Of 1450 pregnant women enrolled, 350 (24%) had HIV. About 1216 (84%) were retained at delivery, 3 of whom delivered <16 weeks. Of 181 (15%) preterm deliveries, 120 (66%) were spontaneous, 56 (31%) were provider-initiated, and 5 (3%) were unclassified. In standardized analyses using inverse probability weighting, maternal HIV increased the risk of spontaneous PTB [RR 1.68; 95% confidence interval (CI): 1.12 to 2.52], but this effect was mitigated on overall PTB [risk ratio (RR) 1.31; 95% CI: 0.92 to 1.86] owing to a protective effect against provider-initiated PTB. HIV reduced the risk of preeclampsia (RR 0.32; 95% CI: 0.11 to 0.91), which strongly predicted provider-initiated PTB (RR 17.92; 95% CI: 8.13 to 39.53). The timing of antiretroviral therapy start did not affect the relationship between HIV and PTB.

Conclusion:

The risk of HIV on spontaneous PTB seems to be opposed by a protective effect of HIV on provider-initiated PTB. These findings support an inflammatory mechanism underlying HIV-related PTB and suggest that published estimates of PTB risk overall underestimate the risk of spontaneous PTB.
Progression of Cabozantinib-Related Osteonecrosis Mimicking Metastases on Bone Scan
Authors: Xu Guofan , Lu Yang
Published: February 2021

Patient was a 73-year-old woman with metastatic renal cell carcinoma. Bone scan showed multifocal bone metastases. The patient received cabozantinib treatment for more than 1 year. On the follow-up bone scan, the previously biopsy-proven left pelvic bone lesion has improved, whereas the right maxillary lesion showed increased extent and intensity of abnormal radiotracer uptake. Given the different change pattern of these lesions, the right maxillary lesion was further evaluated. Biopsy results confirmed devitalized bone with bacterial colonies overgrowth and without tumor cell, suggestive of medication-related osteonecrosis.
Panniculectomy Performed in Conjunction With Gynecologic Surgery in Obese and Morbidly Obese Patients
Authors: Nag Shayoni , Patel Tirth , Gaughan John P. , Bonawitz Steven C.
Published: February 2021

Introduction

Panniculectomy is a common procedure in plastic surgery, often performed after massive weight loss and in morbidly obese patients. It is also performed in combination with various gynecologic procedures based on the rational that it will reduce complication rates and benefit the patient (Am J Obstet Gynecol, 2000. 182, 1502–1505; J Gynecol Technol, 1997;3:9–16; J Am Coll Surg, 1995). These and other studies fail to provide proof of these claims for a number of reasons, including study design, lack of a control group and the inclusion of nonmorbidly obese patients (J Am Coll Surg, 1995; Gynecol Oncol, 1998, 70, 80–86; Int J Gynecol Cancer, 2015;25(8):1503–1512). Recent medical practice has focused increasingly on minimizing patient morbidity and trends in reimbursement are moving toward penalizing practices, which increase complications. The aim of this study was to evaluate the premise that the addition of panniculectomy to gynecologic surgery in the obese and morbidly obese patient population results in a statistically significant improvement in measureable outcomes.

Methods/Results

The American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database was reviewed to assess the association of complications with panniculectomy combined with gynecologic surgery in the morbidly obese patient population. The query identified 296 patients with a body mass index greater than 30 who had panniculectomy concomitant with gynecologic surgery. The results demonstrated a statistically significant relationship (P < 0.05) of these concomitant procedures with superficial infection, wound infection, pulmonary embolism, systemic sepsis, return to operating room, length of operation and length of stay. A systematic review of the literature was then performed which identified only 5 studies that included comparative cohorts of those with gynecologic surgery, with and without panniculectomy. There was no significant benefit across the studies in measured paramters.

Conclusions

This NSQIP study and systematic review of the existing literature does not support the premise that there is a statistically significant benefit associated with performing panniculectomy in conjunction with gynecologic surgery in the morbidly obese patient population. The NSQIP data demonstrate significant elevation of negative outcomes in morbidly obese patients undergoing combined procedures. In the light of the risks to patients and current direction of medical practice the addition of elective panniculectomy to gynecologic surgery should be reevaluated in the a patient population with a body mass index greater than 30.
Successful Treatment of a Nail Gun Injury in Right Parietal Region and Superior Sagittal Sinus
Authors: Wang An Shuo , Zeng Ming Hui , Wang Fei
Published: February 2021

Background Introduction:

Nail injuries are important causes of penetrating craniocerebral injuries. Theirs incidence is very low, but the injuries can be fatal. Since the nail gun was gradually popularized in 1959, the incidence of nail injuries has been increasing. Here we report a case of nail gun injury to superior sagittal sinus and review the literature of the past 60 years to find out what are the possible factors of nail gun injury and what are their respective ratios?

Clinical Report:

An 18-year-old male patient was accidentally injured in the head by the worker's nail gun, accompanied by scalp pain, no physical sensation disorder, and consciousness disorder. A computed tomography scan of his skull showed the penetrating site at the right frontal area, near the superior sagittal sinus. Seven days later, the patient underwent a successful surgery without neurological sequelae.

Discussion:

Nail injuries are rare, but can be potentially fatal. We found that nail guns were the main cause of nail injuries, and other causes include occupational injury, violence, lack of supervision of young children (potential for domestic violence, and child abuse), mental illness, and suicide attempts. While paying attention to the anatomical location of trauma, clinicians should also think more about the possibility of injury so as to provide better help to patients in time.
Single Layer and Double Layer Duraplasty for the Management of Persistent Cerebrospinal Fluid Rhinorrhea Following Frontal Sinus Trauma: A Retrospective Study
Authors: Sahoo Nanda Kishore , Thakral Ankur , Carvalho AS. , Gulati Prachi
Published: February 2021

Persistent cerebrospinal fluid (CSF) rhinorrhea is an infrequent complication of frontal sinus trauma. It often require craniotomy for dural repair and obliteration of sinus with well vascularized pericranial flap. The multilayer vascularized techniques have gained popularity over the years owing to low rate of postoperative CSF leaks. The study retrospectively analyzed 25 frontal sinus trauma patients (20 males, 5 females) of mean age 32 ± 10.23 years with persistent CSF rhinorrhea from January 2011 to December 2018. All patients underwent frontal craniotomy and duraplasty was done with pericranial flap alone in 14 patients (Group I) and in combination with fascia lata graft in 11 patients (Group II). The clinical outcomes of single and double layer dural reconstruction techniques in management of CSF leak were analyzed. The size of defects ranged between 3 to 28 mm. Significant association was present between defect size and reconstruction technique with large defects underwent double layer repair. Two patients developed CSF leak following repair with pericranial flap alone. The rate of successful closure of CSF fistula was 100% with double layer reconstruction technique. However, statistically no significant association was noted between postoperative CSF leak and reconstruction technique. There was no evidence of meningitis, subdural hematoma, intracranial abscess, and mucocele formation in all patients during follow-up of 50.7 ± 23.6 months. To conclude, pericranial flap is a reliable reconstruction material for management of post traumatic frontal sinus CSF leaks. Dual flap technique that combine the use of fascia lata provides comprehensive solution of CSF fistula repair.
The Harvest of a Lateral Segment of Costal Cartilage for Treating Nasal Deformities
Authors: Jiang Jiang , Fan Xu-Hui , Yue Lei , Jia Zhi-Yu , Yang Wei , Zhao Yun-Zhuan , Liu Ji-Lun , Liu Yao-Qiang , Zhang Ying-Huai
Published: February 2021

Background:

Although costal cartilage has many uses and is a reliable source of cartilage for rhinoplasty procedures, donor-site complications may arise with conventional harvesting techniques. The present report reports a novel technique of harvesting costal cartilage using a specially designed scalpel and studies the use of the harvested cartilage in the reconstruction of secondary nasal deformities in patients with cleft lips.

Methods:

Ten patients (7 females and 3 males) with nasal deformities secondary to cleft lip underwent rhinoplasty using this new technique at the Department of Oral and Maxillofacial Surgery, Second Hospital of Hebei Medical University, China, between May 2011 and December 2013. Clinical outcomes were evaluated with a follow-up period of 6 to 30 months.

Results:

The new technique successfully corrected primary nasal deformities, including flat nasal tip, short columella, flaring alae, and asymmetrical nostrils. Surgeons and patients assessed the outcome to be either good or satisfactory. Patients experienced transient discomfort at the wound site but there were no major complications (such as wound infection, dehiscence, exposure, graft extrusion, and pulmonary involvement).

Conclusions:

The novel technique can harvest a lateral segment of costal cartilage for use in the reconstruction of nasal deformities secondary to cleft lip in a one-stage procedure, with minimal donor-site morbidity.
Orbital Fractures and Air Travel
Authors: Riordan Edward A. , van der Rijt Rhys G. , Kernohan Michael D.
Published: February 2021

Previous surveys indicate that the majority of clinicians recommend avoidance of air travel for a period of time following an acute orbital fracture. This advice has largely been based on the theoretical risk that in-flight pressure variation may exacerbate orbital emphysema and produce visual compromise, though no previous reviews have been conducted on the evidence underpinning this advice. The purpose of this study was, therefore, to conduct a systematic review of the literature pertaining to the safety of air travel in the setting of an acute orbital fracture. A systematic review of the OVID Medline database – and of cases referenced as providing evidence for adverse outcomes due to flying with an orbital fracture – was carried out.

Two articles were identified from the literature with data specific to patients who undertook air travel following orbital fractures. A large case series identified no complications in patients exposed to both pressurized and unpressurized air travel, and only a single case report detailed an adverse outcome requiring intervention. The remainder of the articles that had previously been cited as evidence against air travel involved additional factors such as intra-ocular pathologies. There is, therefore, a paucity of evidence to support the conventional advice regarding avoidance of air travel, though clinicians should exclude the possibility of an associated intra-ocular injury, advise against nose-blowing in flight, and provide advice regarding alternative methods to the Valsalva maneuver for equalizing middle ear pressure in flight.

Level of Evidence:

IV
Repair of Defects in the Scalp and Face With Expanded Superficial Temporal Artery Flaps: A Single-Center Retrospective Study
Authors: Ni Xiao-Dong , Xu Yuan , Wang Min , Xu Meng-Nan , Sun Li-Ming , Cui Lei , Yuan Si-Ming
Published: February 2021

Background and Objective:

Defects resulted from the removal of large scars, benign tumors, severe pigmentation abnormalities, and vascular malformations, etc., in the scalp and face need to be repaired to restore the appearance. Here, the authors introduced the application of various expanded superficial temporal artery (STA) flaps in the repair of above defects.

Methods:

From Jan. 2015 to Dec. 2018, 19 patients with craniofacial secondary defects received the repair with expanded STA flaps in our clinic. The defects were resulted from the removal of scalp scar (n = 6), neurofibroma (n = 4), sebaceous nevus (n = 3), arteriovenous malformation (n = 2), facial scar (n = 2), and port-wine stain (n = 2). The expanded STA flaps included 14 cases of flaps pedicled by parietal branch of STA, 2 cases of flaps pedicled by parietal branch of STA combined with laser hair removal, 1 case of flaps pedicled by frontal branch of STA, and 2 cases of prefabricated expanded skin flap with the superficial temporal fascia in the neck.

Results:

The two-stage operation and water-filling expansion were accomplished in all patients. All flaps survived well, except one flap with venous congestion, which resolved after blood-letting and application of drugs promoting venous draining. In the three to six months follow-up, the flaps’ color, texture, and thickness were satisfying.

Conclusions:

Individual application of different types of expanded STA flaps could achieve ideal results in repairing craniofacial secondary defects.