bluuebunny/crossref_metadata_2025 huggingface dataset:
Does docetaxel matter in metastatic gastric cancer? FOLFOX versus FLOT regimens as first-line treatment
Authors: Gürler Fatih , İlhan Ayşegül , Güven Deniz Can , Turhan Okan , Kurt İnci Bediz , Sütçüoğlu Osman , Yildiz Fatih , Arik Zafer , Öksüzoğlu Berna , Yalçin Şuayib , Özdemir Nuriye , Yazici Ozan , Özet Ahmet
Published: July 2021

We aimed to compare the efficacy and the safety of the FOLFOX and the FLOT regimens in metastatic gastric cancer (mGC) as first-line treatment. It was a retrospective multicenter observational study. The comparisons between groups were conducted in terms of progression-free survival (PFS), overall survival (OS), objective response rate (ORR) and hematologic adverse events. Seventy-nine patients, diagnosed with mGC between March 2012 and December 2019, treated with FOLFOX (n = 43) or FLOT (n = 36) regimens as first-line treatment were included in the study. The mPFS was 10.9 months [95% confidence interval (CI), 5.8–16.1] in the FLOT arm and 7.1 months (95% CI, 5.1–9.1) in the FOLFOX arm (P < 0.001). The ORR was 63.9% in the FLOT arm and 30.2% in the FOLFOX arm (P = 0.003). The mOS was 13.3 months (95% CI, 11.3–15.4) in the FLOT arm and 10.9 months (95% CI, 8.2–13.5) in the FOLFOX arm (P = 0.103). The hematologic adverse events in all grades were 88.4% (n = 38) in the FOLFOX arm compared with 80.6% (n = 29) in the FLOT arm (P = 0.335). The FLOT regimen might be a preferred option in mGC with an improved PFS and ORR compared with the FOLFOX regimen.
Osimertinib is an effective epidermal growth factor receptor-tyrosine kinase inhibitor choice for lung cancer with epidermal growth factor receptor exon 18–25 kinase domain duplication: report of two cases
Authors: Zhang Long-Dan , Gao Han , Qin Shou-Ming , Zeng Qian , Chen Quan-Fang
Published: July 2021

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are an effective treatment for common EGFR mutations in non–small-cell lung cancer (NSCLC). Rarer EGFR mutations such as kinase domain duplications (KDDs) have been identified, but the optimal therapy following treatment resistance remains unknown. We report two patients who were diagnosed with NSCLC including KDD. For case 1, afatinib (40 mg once daily) was at first effective but then became ineffective. Consequently, osimertinib therapy (80 mg once daily) was administered. As of 26 May 2021, the osimertinib therapy achieved a stable disease state according to the chest computed tomography scan. As for case 2, the patient received second-line chemotherapy and anlotinib (12 mg once daily) for 6 months and died in May 2020. Here, we describe osimertinib as an effective therapy for EGFR-KDD positive lung adenocarcinoma and thereby provide a new alternative for further treatment following resistance to first- and second-generation EGFR-TKIs.
ZNF668: a new diagnostic predictor of kidney renal clear cell carcinoma
Authors: Wei Chuang , Gao Yijun , Chen Xiatian , Zhao Cheng , Li Peifeng
Published: July 2021

The most common pathological subtype of renal carcinoma is RCC, and its development is closely related to immune infiltration. In our study, we investigated the relationship between zinc finger protein 668 and the prognostic risk, clinical characteristics, overall survival and related pathways. We analyzed the association between ZNF668 and immune cell infiltration through the TIMER database. The results showed that the expression of ZNF668 in RCC was higher than that in normal tissues (P < 0.001). The high expression of ZNF668 is clinically relevant, such as tumor stage (P = 0.001) and TNM classification (T: P = 7.37 e-04; N: P = 0.008; M: P < 0.001). Survival analysis showed that patients with high ZNF668 expression had a significantly poor prognosis (P = 0.023). Univariate analysis showed a significant decrease in overall survival in RCC patients with high ZNF668 expression (P = 0.023). Immuno-cell infiltration showed a significant decrease in CD4+ T cell and dendritic cell infiltration in RCC patients with high expression of ZNF668. GO/KEGG analysis showed that multiple pathways were differentially enriched in the high expression pathway of ZNF668, such as complement activation, and estrogen signaling pathway. In conclusion, high ZNF668 expression is a predictor in RCC.
Advances in management of nonendometrioid endometrial carcinoma, with an emphasis on the sentinel lymph node technique
Authors: Eriksson Ane Gerda Z. , Mueller Jennifer J.
Published: July 2021

Purpose of review

During the last few years there have been important advances in our understanding of endometrial cancer biology, staging, and therapy. In this article, we discuss updates and controversies in the treatment of nonendometrioid endometrial carcinoma (non-EEC), with an emphasis on the role of sentinel lymph node (SLN) biopsy.

Recent findings

Lymph node involvement is an important factor in determining prognosis and guiding adjuvant therapy in endometrial carcinoma. SLN biopsy has emerged as a less morbid alternative to lymphadenectomy in surgical staging, and it has generally gained acceptance in the setting of low-grade endometrial carcinoma; however, its role in the setting of high-grade disease remains a topic of debate. Several prospective studies have demonstrated the accuracy of SLN biopsy in detecting nodal metastasis in high-grade endometrial carcinoma. Retrospective series have compared oncologic outcomes of patients with high-grade disease, surgically staged by SLN biopsy, to those staged with lymphadenectomy, and have reported similar survival outcomes. Prospective data on survival is lacking.

Currently, there is sufficient data to support the diagnostic accuracy of SLN biopsy in the surgical staging of non-EEC. The retrospective evidence demonstrates similar survival for SLN biopsy versus lymphadenectomy.
Patient-specific preprocedural planning for tricuspid valve repair and replacement procedures
Authors: Vukicevic Marija , Faza Nadeen N. , Little Stephen H.
Published: July 2021

Purpose of review

Despite the prevalence of tricuspid valve regurgitation disorders, isolated interventions on tricuspid valves were previously infrequent due to high mortality rates and lack of advanced clinical imaging technology. Due to advancements in cardiovascular imaging and interventional technologies tricuspid valve repairs and replacement interventions became increasingly more attainable.

Recent findings

Noninvasive clinical imaging of the tricuspid valve can be challenging, providing anincomplete assessment of unique tricuspid anatomy. 3D printing technology represents an additional tool for more comprehensive preprocedural planning of tricuspid interventions and observation of tricuspid valve geometry. Patient-specific 3D printed replicas of tricuspid valve apparatus are especially useful in highly complicated cases, where physiological tricuspid replicas allow benchtop observation of individual patient's anatomy, device implantation in physiological tricuspid valves and interactions of devices with native tricuspid tissue, frequently leading to optimization or change in operational strategy.

Comprehensive use of clinical imaging including echocardiography, computed tomography, and cardiac magnetic resonance along with 3D printed modeling is key to successful tricuspid repair and replacements. Patient-specific 3D printed models of tricuspid anatomy can facilitate preprocedural planning, educate patients and clinicians, and improve device design, leading to the overall improvement of patients’ outcomes and care.
The current landscape of lipoprotein(a) in calcific aortic valvular disease
Authors: Hsieh Grace , Rizk Theresa , Berman Adam N. , Biery David W. , Blankstein Ron
Published: July 2021

Purpose of review

Calcific aortic stenosis (CAVS) is the most common form of valvular heart disease in developed countries, increasing in prevalence with the aging population. Surgical or transcatheter aortic valve replacement is the only treatment available for CAVS. However, these interventions are typically reserved for severe symptomatic aortic stenosis (AS). The purpose of this review is to summarize the recent literature in uncovering the underlying pathophysiology of CAVS in the setting of lipoprotein (a) [Lp(a)] and emerging therapies targeting Lp(a) which may help halt disease progression in CAVS.

Recent findings

Pathophysiologic, epidemiological, and genetic studies over the past two decades have provided strong evidence that Lp(a) is an important mediator of calcific aortic valvular disease (CAVD). Studies suggest that Lp(a) is a key carrier of pro-calcifying oxidized phospholipids (OxPL). The metabolism of OxPL results in a pro-inflammatory state and subsequent valvular thickening and mineralization through pro-osteogenic signaling. The identification of Lp(a) as a causal mediator of CAVD has allowed for opportunities for emerging therapeutic agents which may slow the progression of CAVD (Fig. 1

JOURNAL/cocar/04.03/00001573-202109000-00007/figure1/v/2023-09-11T232128Z/r/image-jpeg

).

This review summarizes the current knowledge on the association of Lp(a) with CAVD and ongoing studies of potential Lp(a)-lowering therapies. Based on the rate-limiting and causal role of Lp(a) in progression of CAVS, these therapies may represent novel pharmacotherapies in AS and inform the developing role of Lp(a) in the clinical management of CAVD.
Accuracy of a new instrument for noninvasive evaluation of pulse wave velocity: the Arterial sTiffness faitHful tOol aSsessment project
Authors: Leone Dario , Buraioli Irene , Mingrone Giulia , Lena Davide , Sanginario Alessandro , Vallelonga Fabrizio , Tosello Francesco , Avenatti Eleonora , Cesareo Marco , Astarita Anna , Airale Lorenzo , Sabia Luca , Veglio Franco , Demarchi Danilo , Milan Alberto
Published: July 2021

Background:

Large artery stiffness, assessed by carotid--femoral pulse wave velocity (cfPWV), is a major risk factor for cardiovascular events, commonly used for risk stratification. Currently, the reference device for noninvasive cfPWV is SphygmoCor but its cost and technically challenging use limit its diffusion in clinical practice.

Aim:

To validate a new device for noninvasive assessment of cfPWV, ATHOS (Arterial sTiffness faitHful tOol aSsessment), designed in collaboration with the Politecnico di Torino, against the reference noninvasive method represented by SphygmoCor.

Methods:

Ninety healthy volunteers were recruited. In each volunteer, we assessed cfPWV, using SphygmoCor (PWVSphygmoCor) and ATHOS (PWVATHOS) devices in an alternate fashion, following the ARTERY Society guidelines. The accuracy was assessed by Bland--Altman plot, and reproducibility was assessed by interoperator correlation coefficient (ICC).

Results:

Mean PWVATHOS and mean PWVSphygmoCor were 7.88 ± 1.96 and 7.72 ± 1.95 m/s, respectively. Mean difference between devices was 0.15 ± 0.56 m/s, with a high correlation between measurements (r = 0.959, P < 0.001). Considering only PWV values at least 8 m/s (n = 30), mean difference was 0.1 ± 0.63 m/s. The ICC was 97.7% with ATHOS

Conclusion:

ATHOS showed an excellent level of agreement with SphygmoCor, even at high PWV values, with a good reproducibility. Its simplicity of use could help increase clinical application of PWV assessment, improving patients’ cardiovascular risk stratification.
European Society of Hypertension position paper on renal denervation 2021
Authors: Schmieder Roland E. , Mahfoud Felix , Mancia Giuseppe , Azizi Michael , Böhm Michael , Dimitriadis Kyriakos , Kario Kazuomi , Kroon Abraham A. , D Lobo Melvin , Ott Christian , Pathak Atul , Persu Alexandre , Scalise Filippo , Schlaich Markus , Kreutz Reinhold , Tsioufis Costas
Published: July 2021

This ESH Position Paper 2021 with updated proposed recommendations was deemed necessary after the publication of a set of new pivotal sham-controlled randomized clinical trials (RCTs), which provided important information about the efficacy and safety of endovascular device-based renal denervation (RDN) for hypertension treatment. RDN is effective in reducing or interrupting the sympathetic signals to the kidneys and decreasing whole body sympathetic activity. Five independent, fully completed, sham-controlled RCTs provide conclusive evidence that RDN lowers ambulatory and office blood pressure (BP) to a significantly greater extent than sham treatment. BP-lowering efficacy is evident both in patients with and without concomitant antihypertensive medication. The average decrease of 10 mmHg in office BP is estimated to lower the incidence of cardiovascular events by 25–30%, based on meta-analyses of RCTs using pharmacological treatment. Neither peri-procedural, nor short-term or long-term adverse events or safety signals (available up to 3 years) have been observed. Implementing RDN as an innovative third option in the armamentarium of antihypertensive treatment requires a structured process that ensures the appropriate performance of the endovascular RDN procedure and adequate selection of hypertensive patients. The latter should also incorporate patients’ perspective and preference that needs to be respected in a shared decision-making process.
Football beats hypertension: results of the 3F (Fit&Fun with Football) study
Authors: Schrader Bastian , Schrader Joachim , Vaske Bernhard , Elsässer Albrecht , Haller Hermann , del Vecchio Alessandro , Koziolek Michael , Gehlenborg Eugen , Lüders Stephan
Published: July 2021

Objective(s):

Football as the most popular sport could improve insufficient physical activity in patients with cardiovascular risk factors. A modified ‘healthy’ football training format could motivate hypertensive patients to return to sport and improve risk factors.

Methods:

The 3F study: ‘Fit and Fun with Football’ a prospective interventional study with 1 year follow-up. Football group: n = 103, structured ‘health’-football training (1×/week, 90 min) led by Deutscher Fußball Bund-licensed football coaches. Hypertensive patients at least 45 years who have not exercised for several years were compared with a control group (n = 105).

Primary study objective:

Reduction of office (OBP) and/or 24-h ambulatory blood pressure (BP) monitoring (ABPM) and/or reduction of number or dosage of antihypertensive medication.

Main results:

OBP values decreased significantly in the football group from 142.6/87.9 to 130.8/81.8 mmHg (P < 0.001), in the control group the values increased slightly (NS). ABPM values decreased significantly in the football group, while a slight increase was found in the control group. At the end of the study, the mean values in the football group of both OPB (P < 0.001) and ABPM (systolic P < 0.001, diastolic P = 0.017) were significantly lower than in the control group. Significantly more people in the football group were able to reduce antihypertensive patients than in the control group (football group:16, control group:6), while more participants in the control group intensified antihypertensive therapy (football group:3, control group:14) (P < 0.001). Among the secondary endpoints, there was a weight loss of 3 kg in the football group and an increase of 1.7 kg in the control group (P < 0.001).

Conclusion:

Offering modified ‘healthy’ football-training to middle-aged hypertensive patients can lead to better BP control and a reduction of antihypertensive medication. Therefore, the offer of ‘health football’ should be established and supported by clubs, insurances and authorities.
Relation Between Body Mass Index and Dry Eye Disease: The Japan Public Health Center–Based Prospective Study for the Next Generation
Authors: Yamanishi Ryutaro , Sawada Norie , Hanyuda Akiko , Uchino Miki , Kawashima Motoko , Yuki Kenya , Tsubota Kazuo , Kato Tadahiro , Saito Isao , Arima Kazuhiko , Mizukami Satoshi , Tanno Kozo , Sakata Kiyomi , Yamagishi Kazumasa , Iso Hiroyasu , Yasuda Nobufumi , Shimazu Taichi , Yamaji Taiki , Goto Atsushi , Inoue Manami , Iwasaki Motoki , Tsugane Shoichiro ,   for the JPHC-NEXT Group
Published: July 2021

Objective:

To investigate the relation between body mass index (BMI) and dry eye disease (DED).

Methods:

We conducted a cross-sectional questionnaire-based survey in 85,264 Japanese men and women aged 40 to 74 years who participated in the Japan Public Health Center–based Prospective Study for the Next Generation (JPHC-NEXT Study). Dry eye disease was defined as the presence of severe symptoms or clinical diagnosis. A multivariable logistic regression model was used to estimate the odds ratios (ORs) of DED associated with BMI and their two-sided 95% confidence intervals (CIs). We adjusted for age, cohort area, visual display terminal time, smoking status, alcohol intake, education status, income status, as well as history of hormone replacement therapy for women.

Results:

Prevalence of DED was 23.4% (n = 19,985; 6,289 men, 13,696 women). Higher BMI was correlated with a lower prevalence of DED in a dose–response fashion, with an adjusted OR of DED (95% CI) per 1 kg/m2 increment of BMI of 0.98 (95% CI: 0.97–0.99) for men and 0.97 (95% CI: 0.97–0.98) for women.

Conclusions:

This large population-based study showed an inverse relationship between BMI and prevalence of DED in a Japanese population. Underestimation of DED is warned, especially for participants with high BMI.
Changes in Limbal Optical Coherence Tomography Angiography Outcomes in Patients With Overnight Contact Lens Wear
Authors: Bostanci Ceran Basak , Ozates Serdar , Arifoglu Hasan Basri , Tasindi Emrullah
Published: July 2021

Objectives:

To evaluate the perilimbal vasculature of patients who wear contact lenses (CLs) overnight with optical coherence tomography angiography (OCTA) and compare the results with healthy population.

Methods:

Forty-two patients were included in this observational study. The OCTA imaging was performed in the temporal quadrant of the perilimbal region using a swept-source optical coherence tomography system (Triton DRI-OCT; Topcon Corporation, Tokyo, Japan). The assessments were made in two depths: starting from the conjunctival epithelium to 200 μm scleral depth and the scleral depth between 200 and 1,000 μm. The vessel density, vessel length density, vessel diameter index, and fractal dimension were the main outcomes and compared between overnight CL users and healthy population.

Results:

Twenty-two patients who have been using CLs overnight for at least 3 months and 20 healthy individuals were included in the study. The vessel density at the superficial layer was significantly higher in the CL group compared with the control group (P<0.001). Vessel diameter index, vessel length density, and fractal dimension at the superficial layer did not differ between the groups (P>0.05 for all). There was no difference in the vessel density, vessel diameter index, vessel length density, and fractal dimension in the deep layer between the groups (P>0.05 for all).

Conclusions:

Patients who use CL overnight exhibit increased vessel density in the superficial layers of the perilimbal region, which may suggest new vessel formation in the conjunctiva. Anterior segment OCTA may be useful to evaluate the initial changes in limbal vasculature in CL users.
Quality-of-Life Improvement After Scleral Lens Fitting in Patients With Keratoconus
Authors: Baudin Florian , Chemaly Alicia , Arnould Louis , Barrénéchea Elsa , Lestable Lolita , Bron Alain M. , Creuzot-Garcher Catherine
Published: July 2021

Objectives:

To assess the quality-of-life improvement after scleral lens fitting in patients with keratoconus.

Methods:

We conducted a prospective observational study of all consecutive patients with keratoconus starting scleral lens fitting in 2019, from January 2 to December 27, at the Dijon University Hospital, France. Quality of life was assessed before and after wearing scleral lenses for 3 months through the National Eye Institute Visual Function Questionnaire 25 (NEI-VFQ 25) questionnaire. We investigated factors potentially influencing quality of life: final visual acuity, keratoconus stage, and maximum keratometry reading.

Results:

In total, 41 eyes of 24 patients were successfully fitted with scleral lenses, 92.9% were 18 mm in diameter and 7.1% were 17 mm. The visual acuity improved by −0.4±0.3 logarithm of the minimum angle of resolution (P<0.001) after scleral lens fitting. Visual gain increased with keratometry and keratoconus severity (P<0.001; P<0.01). The NEI-VFQ 25 score increased by 19.5±19.1 points on average (P<0.001). No association was found between the factors under study and improvement in quality of life.

Conclusion:

Our study confirms the functional improvement in patients with keratoconus fitted with scleral lenses, especially in patients with more advanced disease. Moreover, it suggests a major role of these lenses in improving quality of life, independently of the severity of the disease and the visual gain.
Diagnostic accuracy of the Pain (P), Enjoyment (E), and General activity (G) scale, a three-item questionnaire, for grading the impact of orofacial pain-related dysfunction
Authors: Roldán-Majewski Carolina , Broedel Elias , von Korff Michael , Rammelsberg Peter , Schindler Hans Jürgen , Giannakopoulos Nikolaos Nikitas
Published: July 2021

Purpose of this study was to examine the discriminative properties of the 3-item Pain (P), Enjoyment (E), and General activity (G) (PEG) questionnaire for grading impact of nondental orofacial pain. Two hundred eighty-six consecutive patients with orofacial pain of nondental origin filled out the PEG questionnaire and Graded Chronic Pain Scale (GCPS, version 2). Correlation between the PEG and GCPS scores, internal consistency of the PEG, and differences between groups were examined statistically (level of significance: P ≤ 0.05). The mean (±SD) age of the 213 patients (158 female) who were included in the analysis was 43.1 (±16.7) years. Of the sample, 48.8% (n = 104) had some degree of orofacial pain-related disability (mean overall characteristic pain intensity: 51.2 ± 23.2, average overall PEG score: 4.3 ± 2.7, and average PHQ-9 score: 8.2 ± 6.5). No significant differences were found between the sexes for any score. The number of disability points (GCPS) and overall PEG score showed a strong and positive correlation (Spearman ρ = 0.77, P < 0.001). The internal consistency of the PEG questionnaire was high (Cronbach α = 0.86). Assuming 3 different levels of orofacial pain-related disability (mild, moderate, and severe), we obtained overall accuracy of 69.01%, with high specificity for mild and severe cases. The 3 PEG groups (mild, moderate, or severe) differed from each other significantly regarding their clinical grading according to the GCPS (Kruskal–Wallis, P < 0.001). Analysis of the receiver operating characteristic curve showed that a single cutoff value of 3.8 points in the PEG score yields adequate validity (sensitivity = 0.91 and specificity = 0.78). The proposed 2 cutoff points (upper = 7 and lower = 4) yield low sensitivity for the upper threshold. The 3-item PEG questionnaire is suitable for grading impact of nondental orofacial pain.
Treatment of Pulmonary Carcinoid Tumors With Bronchoscopic Cryotherapy
Authors: Perikleous Periklis , Mayer Nora , Finch Jonathan , Beddow Emma , Anikin Vladimir , Asadi Nizar
Published: July 2021

Background:

Pulmonary carcinoids are rare tumors originating from neuroendocrine cells in the lungs. Because of their potentially infiltrative nature, surgical resection remains the treatment of choice. However, not all patients with technically resectable disease will be able to undergo surgery, primarily because of poor lung function or medical co-morbidities. Centrally located, intraluminal tumors have been reported to be amenable to bronchoscopic treatment. We specifically examined the role of cryotherapy in the treatment of bronchial carcinoid tumors.

Methods:

Sixty-three patients (52.38% female) who underwent a combined total of 243 cryotherapy procedures for treatment of bronchial carcinoid between 1992 and 2020 in our institution were included in the study. Following discussion in multidisciplinary meetings, patients were considered for first-line cryotherapy when lung resection was deemed not possible or when they had rejected surgery.

Results:

Cryotherapy resulted in complete remission in 21 (33.33%) patients with maximum tumor diameter less than 20 mm (mean: 11.08 mm, 95% confidence interval: 8.76-13.40), and allowed 22 (34.92%) patients with larger lesions (mean: 24.04 mm, 95% confidence interval: 18.78-29.30) to proceed with parenchymal sparing resections. Marked symptomatic relief (P<0.001) was reported by 58 (92.06%) patients. The median follow-up was 33 months (range: 0 to 243 mo). One (1.59%) patient was diagnosed with recurrence in a contralateral lobe 3 years after surgery and was treated with radiofrequency ablation.

Conclusions:

In the absence of a definitive randomized controlled trial comparing bronchoscopic treatment with surgical resection, we provide evidence on the safety and efficacy of cryotherapy and encourage wider adoption of this inexpensive and minimally invasive technique for treatment of bronchial carcinoids.
Left Ventricular Flow Dynamics with the HeartMate3 Left Ventricular Assist Device: Effect of Inflow Cannula Position and Speed Modulation
Authors: Ortiz Sean , Vu Vi , Montes Ricardo , May-Newman Karen
Published: July 2021

Improper left ventricular assist device (LVAD) inflow cannula (IC) positioning creates areas of stasis and low pulsatility that predispose thromboembolism, but may be mitigated with LVAD speed modulation. A mock loop study was performed to assess the sensitivity of left ventricle (LV) flow architecture to IC position and speed modulation during HeartMate3 support. System pressure, flow, and the time-resolved velocity field were measured within a transparent silicone LV for three IC angles and three IC insertion depths at matched levels of cardiac function and LVAD speed. Inflow cannula angulation towards the septum increased the resistance to LVAD flow as well as increasing the size and energy of the counter-clockwise (CCW) vortex. Apical velocity was reduced compared to IC angulation towards the mitral valve, but regional pulsatility was maintained across all angles and LVAD speeds. Increased IC protrusion decreased LVAD flow resistance, increasing velocity within the IC but reducing flow and pulsatility in the adjacent apical region. Increasing LVAD flow resistance improves aortic valve opening and strengthens the CCW vortex which directs inflow towards the septum, producing higher blood residence time and shear activation potential. Despite this impact on flow architecture, pulsatility reduction with increased LVAD speed was minimal with the HeartMate3 speed modulation feature.
Two heterozygous mutations associated with type I protein C deficiency in two Chinese independent families
Authors: Xu Qiyu , Wang Mingshan , Jin Yanhui , Liu Siqi , Luo Shasha , Yang Lihong
Published: July 2021

To explore the pathogenesis of protein C (PC) deficiency in two independent families by mutations detection and bioinformatics analysis. The PC activity (PC:A) and PC antigen (PC:Ag) were detected by chromogenic substrate and ELISA, respectively. The PROC sequencing was performed to identify the mutational sites. The molecular pathogenesis of the mutations were studied by the conservation, bioinformatics and model analysis. The PC:A and PC:Ag of the proband 1 were observably reduced at 35 and 44%, respectively. Gene sequencing analysis revealed the p.Leu278Pro derived from a heterozygous c.833T>C point mutations in exon 9 of PROC gene. For proband 2, the PC:A and PC:Ag were decreased to 40 and 51%, respectively, caused p.Ala178Pro missense mutation by a heterozygous point mismatch of c.532G>C in exon 5 of PROC gene. Bioinformatics and model analysis indicated that it was the Leu278Pro and Ala178Pro that caused clinical PC deficiency (PCD). The heterozygous mutations Leu278Pro and Ala178Pro were observed in two independent families. The Leu278Pro mutation in the PROC gene has not been described elsewhere. The two mutations can both lead to the type I hereditary PCD, and probably be the major causes of PCD in the families.
Pediatric sarcoidosis with diagnostic and therapeutical insights
Authors: Sergi Consolato M.
Published: July 2021

Purpose of review

Sarcoidosis is a chronic granulomatous disorder involving multiple systems and organs of undefined etiology. Although most of the morbidity relies upon lung disease, the function of several systems and organs can be affected. The natural history of lung disease consists of pulmonary involvement. An exaggerated and abnormal inflammatory response accompanies this aspect. There are noncaseating confluent epithelioid granulomas and, potentially, a progressive airway obstruction ab externo. As the disease is multisystemic, there is an increased likelihood of complications that may be serious and even fatal.

Recent findings

The American Thoracic Society (ATS) Core Curriculum updates clinicians annually in adult and pediatric lung disease, critical medical care, and sleep medicine. In late 2020, the ATS targeted sarcoidosis. Also, in 2019, the French Sarcoidosis Group thoroughly revised the literature on pediatric sarcoidosis. Currently, staging is based on chest radiograph findings, and the most commonly used system is the Scadding classification, which has been applied to both children and adults alike. Treatment may consist of oral or pulsed intravenous corticosteroids, but it should be implemented in union with a rheumatologist, as there are no randomized controlled studies in children.

Sarcoidosis is rare in childhood. Diagnosis is complex and relies on multiple diagnostic modalities with both staging and therapy progressively mirroring the sarcoidosis, which affects adults. In the majority of patients, spontaneous resolution will occur and observation is justified above treatment. Nevertheless, in case treatment is needed corticosteroids remain the mainstay of the treatment in some pediatric patients. Relapses are not uncommon and a long-term follow-up is essential.
Vitamin C for Sepsis and Septic Shock
Authors: Ammar Mahmoud A. , Ammar Abdalla A. , Condeni Melanie S. , Bell Carolyn M.
Published: July 2021

Background:

Sepsis remains a leading cause of death in the critically ill. The combination of thiamine, vitamin C, and hydrocortisone has recently emerged as a potential adjunctive therapy and supportive care for patients with sepsis and septic shock.

Areas of Uncertainty:

Several randomized and observational controlled trials evaluated the role of vitamin C in sepsis and septic shock. However, there are variabilities in the findings of these studies that led to a substantial global debate on incorporating vitamin C therapy in clinical practice.

Data Sources:

A PubMed and Embase English language literature search through April 2021 was performed using the following terms: ascorbic acid, vitamin C, corticosteroid, hydrocortisone, thiamine, HAT, sepsis, and shock. Citations, including controlled trials, observational studies, review articles, guidelines, and consensus statements, were reviewed. The risk of bias for each clinical study was systematically evaluated. Relevant clinical data focusing on efficacy, safety, and special considerations regarding the use of vitamin C with and without thiamine and hydrocortisone in sepsis and septic shock were narratively summarized.

Results:

The most commonly used vitamin C dosing in sepsis and septic shock is 1.5 g every 6 hours with and without thiamine and hydrocortisone. Current literature is limited because of heterogeneity in vitamin C regimen used, initiation time, and duration of treatment. This limitation led to variability in outcomes evaluated. Vitamin C decreases proinflammatory mediators and slows the progression of endothelial injury in severe sepsis. There is an inconsistency between randomized controlled trials and observational controlled trials regarding mortality, resolution in organ failure, hospital and intensive care unit length of stay findings with the use of vitamin C in septic shock. Vitamin C seems to be safe in comparison with placebo.

Conclusions:

Future studies with consistent end points, initiation time with an emphasis on early initiation, and standard vitamin C dosing regimen are needed to determine the overall benefit of vitamin C in sepsis.
Secondary stroke prevention in patients with patent foramen ovale
Authors: Rhoades Ruben , Tzeng Diana , Ruggiero Nicholas
Published: July 2021

Purpose of review

Although a patent foramen ovale (PFO) is an established risk factor for cryptogenic ischemic stroke, strategies for secondary prevention remain controversial. Increasing evidence over the past decade from well designed clinical trials supports transcatheter PFO closure for selected patients whose stroke was likely attributable to the PFO. However, patient selection using imaging findings, clinical scoring systems, and in some cases, thrombophilia testing, is crucial for determining patients most likely to benefit from closure, anticoagulation, or antiplatelet therapy.

Recent findings

Recent studies have found that patients with a high Risk of Paradoxical Embolism (RoPE) score and those with a thrombophilia benefit more from closure than medical therapy (including antiplatelet or anticoagulant therapy) alone. Meta-analyses have demonstrated an increased short-term risk of atrial fibrillation in closure patients, and that residual shunt after closure predicts stroke recurrence. Last, recent data have been inconclusive as to whether patients receiving medical therapy only benefit more from anticoagulation or antiplatelet therapy, so this remains an area of controversy.

Transcatheter PFO closure is an evidence-based, guideline-supported therapy for secondary stroke prevention in patients with a PFO and cryptogenic stroke. However, proper patient selection is critical to achieve benefit, and recent studies have helped clarify those patients most likely to benefit from closure.
Change in Incidence and Epidemiology of Inflammatory Bowel Disease in 2‐ to 9‐Year‐olds in Southwest England
Authors: Fernandes Sofia , Spray Christine H. , Whitmarsh Alex , Sandhu Bhupinder K. , Wiskin Anthony E.
Published: July 2021

Objectives:

The aim of the study was to characterize epidemiology, phenotype, and clinical outcome of Inflammatory Bowel Disease (IBD) diagnosed ages 2 to 9 years, and compare age groups 2 to 5 and 6 to 9 years.

Methods:

A population‐based retrospective cohort study of all <10‐year‐olds diagnosed with IBD between 2004 and 2017 in Southwest England was performed. Patients were divided into age groups at diagnosis. Demographics, investigations, and phenotype at diagnosis were collected. Treatments and outcomes were analysed at 1, 2, 5, and 10 years follow‐up. Poisson regression was used for IBD incidence rate ratios; Wald test for variation by age group; parametric/nonparametric tests for phenotype.

Results:

There were 666 new paediatric IBD (pIBD) patients ages ⩽16 years, from which 136 were 2 to 9 (2–5 years: 32; 6–9 years: 104). Incidence of pIBD increased from 4 to 6 cases per 100,000 whereas in A1a group was stable around 2 cases per 100,000. Crohn Disease (CD) children were majority boys, 2‐ to 5‐year‐olds were more likely to have ileal sparing than 6 to 9‐year group but had similar rates of surgery and anti‐TNF therapy. Two‐ to 5‐year‐olds with ulcerative colitis were more likely to have surgery but rates for anti‐TNF therapy were similar. Sixteen percent of 2‐ to 5‐year‐olds and 10% of 6‐ to 9‐year‐olds had IBD‐unclassified. No significant differences in symptoms or time to diagnosis were found.

Conclusions:

Twenty percent of pIBD in Southwest England are 2 to 9 years old. pIBD incidence has increased but is stable in that group. In terms of phenotypic differences, ileal sparing in CD and pancolitis and surgery in UC, are more likely in 2‐ to 5‐year‐olds.
Understanding and Responding to the Impact of COVID‐19 on Paediatric Gastroenterology Training & Practice of Young ESPGHAN Members
Authors: Niţă Andreia F. , Tsita Despina , Grima Anne‐Marie , Cameron Fiona , Rock Nathalie M. , Tapsas Dimitrios
Published: July 2021

Objectives:

Limited data exist about the impact of the coronavirus disease 2019 (COVID‐19) pandemic on the training and clinical practice of young doctors. The aim of this study was to evaluate the impact on paediatric gastroenterologists in training posts during the first wave of the European COVID pandemic.

Methods:

All Young members of European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) (YE) members received a multiple‐choice questionnaire concerning the impact (if any) on their clinical practice, mental health, quality of care provided and fellowship/training experience. The survey was conducted between May 22, 2020 and June 10, 2020.

Results:

Of the 144 responders (40% of YE members), 85% (n = 123) reported an impact of COVID‐19. Ninety‐six percent reported an impact on their clinical practice, including more virtual patient consultation (n = 91), underutilization of ambulatory care (n = 113) and reduced or lack of planned admissions (n = 75). Endoscopy restrictions to semi‐urgent or emergency cases were reported in 82 and lack of medical equipment/drugs (n = 47) were also reported.

Reported adverse mental health issues included poor concentration, increased stress levels, an impact on family life in 62% and a reduced quality of care in 45%; this was more often reported in doctors from Southern Europe (54%) than in those from other geographical areas.

Seventy‐seven percent reported an impact on the content of their fellowship, including lack of participation in national/international meetings, withdrawn research time and limited mentoring.

Conclusions:

The impact of the COVID‐19 pandemic has been shown to affect the clinical practice, training and mental health of YE members. Adaptations of training programmes and targeted strategies to improve the clinical practice of young practitioners are needed and proposed in this manuscript.
Insight Into Illness and Psychological Defense Attitudes in People With Chronic Schizophrenia Using Markova's Insight Scale
Authors: Ogawa Yasuhiro , Fukuhara Keita , Tanaka Hiroyuki , Nagata Yuma , Ishimaru Daiki , Urakawa Mizuki , Nishikawa Takashi
Published: July 2021

Insight into illness is a multidimensional phenomenon, and various assessments are available. We focused on Markova's Insight Scale (IS) and investigated the relationship between insight, psychological defenses, and neurocognition in 38 patients with schizophrenia. Results showed that insight was significantly correlated with an immature defense style. Moreover, IS was significantly predicted by immature defense style after adjusting for clinical variables. Although insight is often assumed to be multidetermined with potential contributions from factors such as cognitive function and psychological defensive mechanisms, our results indicated that better insight assessed with the IS is more likely to reflect immature defenses. This may also be reflected in our result that a higher insight score correlated with earlier onset of illness. The insight score may reflect the immature psychological defensive attitudes of schizophrenia and may lead such patients to wish to comply with the views of clinicians.
Meeting Undergraduate Nursing Students' Clinical Needs
Authors: Leighton Kim , Kardong-Edgren Suzan , Schneidereith Tonya , Foisy-Doll Colette , Wuestney Katherine A.
Published: July 2021

Background

Nurse educators expanded replacement of traditional clinical practice and face-to-face simulation experiences with screen-based simulation (SBS) during the COVID-19 (coronavirus disease 2019) pandemic.

Purpose

The purpose of this research was to understand the student experience when learning in 3 types of clinical education environments.

Methods

This quantitative descriptive survey study used the Clinical Learning Environment Comparison Survey 2.0 (CLECS 2.0) to compare prelicensure nursing students' perceptions of learning in 3 clinical learning environments.

Results

The CLECS 2.0 was completed by 113 participants from 3 countries. Most scores were highest for the traditional clinical practice environment, and all were lowest for the SBS environment.

Conclusions

The findings are concerning as discussions about whether SBS can replace traditional clinical practice hours unfolds. The findings support the need for concentrated efforts to improve specific areas of the SBS experience.
A future with no MVC patients? Impact of autonomous vehicles on orthopaedic trauma may be slow and steady
Authors: Childs Benjamin R. , Simson Joshua E. , Wells Matthew E. , Macias Reuben A. , Blair James A.
Published: July 2021

Introduction:

Orthopaedic trauma results in significant patient morbidity. Autonomous vehicle (AV) companies have invested over $100 billion in product development. Successful AVs are projected to reduce motor vehicle collision (MVC)-related injuries by 94%. The purpose of this study was to estimate the timing and magnitude of AV impact on orthopaedic trauma volume.

Methods:

ICD 9 codes consistent with acetabulum (OTA 62), pelvis (OTA 61), hip (OTA 31), femur (OTA 32–33), tibia (OTA 41–43), ankle (OTA 44), and calcaneus (OTA 82) fractures and the proportion of cases caused by MVC were taken from the National Trauma Databank (NTDB) 2009–2016. Regression was performed on estimates of market penetration for autonomous vehicles taken from the literature.

Results:

For NTDB years 2009 to 2016, 300,233 of 987,610 fractures of interest were the result of MVC (30.4%). However, the percentage of MVC mechanism of injury ranged from 9% to 53% depending on fracture type. Regression of estimates of AV market penetration predicted an increase of 2.2% market share per year. In the next 15 years we project 22% market penetration resulting in a 6% reduction in orthopaedic lower extremity trauma volume.

Conclusion:

Adoption of AVs will result in a projected 8% reduction in MVC-related orthopaedic trauma-related injuries over a 15-year period. Although this represents a significant reduction in morbidity, the advent of AVs will not eliminate the need for robust orthopaedic trauma programs. The gradual rate of injury reduction will allow hospitals to adapt and reallocate resources accordingly.
Evaluation of post-production handling practices of monoclonal antibodies throughout the world
Authors: Fayek Rana , Soleyman Mostafa , Jiskoot Wim , Crul Mirjam
Published: July 2021

Introduction:

This survey aimed to create a snapshot of the post-production handling of monoclonal antibodies in daily practice in health-care facilities in several parts of the world.

Methods:

A worldwide web-based survey was distributed among pharmacists between November and December 2020.

The questions were categorized in sections related to storage conditions, reconstitution practices including the use of medical devices, administration practices, transportation, visual examination and shelf-life of mAbs, education of health-care professionals, and patient's home-administration.

Results:

A total of 247 responders from 37 countries around the world participated in the survey. Hospital pharmacists were the largest group of respondents (92%). Most of the respondents (92%) reported that they store the mAbs at 2 to 8°C and 71% protect the prepared ready-to-administer mAbs from light by secondary packaging. The participants used spikes (38%), closed system transfer devices (CSTDs) (12%), and needles (22%) or a combination of these (28%) as a medical device, and 89% perform the reconstitution practices manually, versus 4% by semi-automatic pump system, 1% by robot, and 5% by a combination of these reconstitution methods. The respondents reported that in their institution, after compounding mAbs are transported via a logistic employee on foot at ambient temperature (59%) or in a cool-box (20%), or via the tube system (7%). More than half (64%) do not have written guidelines for transportation, but 86% perform a visual examination for particles of prepared mAbs before administration. Furthermore, 52% of the responders answered that nurses as well as pharmacists and pharmacy assistants receive staff training on the potential risks of mAb handling.

Conclusion:

There is a high level of variability in daily practices of mAb handling in pharmacies worldwide.
ERG Immunoreactivity in Blastic Hematolymphoid Neoplasms: Diagnostic Pitfall in the Workup of Undifferentiated Malignant Neoplasms
Authors: Koo Matthew , Natkunam Yasodha
Published: July 2021

Undifferentiated malignant neoplasms pose diagnostic challenges, and reliable immunohistochemical markers with well-characterized staining profiles are desirable when characterizing them. Our initial observation of erythroblast transformation specific regulated gene-1 (ERG) reactivity in myeloid sarcomas led us to broadly explore the utility of ERG as a marker of immature hematolymphoid neoplasms presenting in extramedullary sites. We stained 207 immature and mature hematolymphoid lesions as well as 39 benign hematolymphoid tissues and found weak-to-moderate ERG immunopositivity in 15 of 16 (94%) acute myeloid leukemias/myeloid sarcomas, including 4 of 5 (80%) CD34-negative/CD117-negative acute myeloid leukemias/myeloid sarcomas. ERG positivity was also seen in all 9 cases of B-lymphoblastic and T-lymphoblastic leukemia/lymphoma, all 3 cases of hematogone hyperplasia, and all 4 cases of systemic mastocytosis. ERG was negative in 148 mature B-cell and T-cell lymphomas, including 2 high-grade B-cell lymphomas and 2 blastoid variant mantle cell lymphomas; 23 histiocytic/dendritic cell neoplasms; 2 indolent T-lymphoblastic proliferations; and 2 blastic plasmacytoid dendritic cell neoplasms. We conclude that ERG immunoreactivity may pose a significant diagnostic pitfall in the workup of undifferentiated malignant neoplasms, particularly those presenting in extramedullary sites.
Increased Expression of the lncRNA NRON Along With NFATc1/PIM-1 in Labial Salivary Glands of Sjögren’s Syndrome Patients
Authors: Horai Yoshiro , Nakamura Hideki , Shimizu Toshimasa , Nishihata Shinya , Iwamoto Naoki , Kuroki Tamotsu , Okano Shinji , Kawakami Atsushi
Published: July 2021

The aim of our study was to analyze the expressions of nuclear factor of activated T cells (NFAT)-related substances including long noncoding RNA NRON which participates in pathophysiology of Sjögren’s syndrome (SS), and to assess the histologic findings in individuals with SS. In this study, the expressions of NRON, NFATc1, CD3/CD4, and proviral integration site for Moloney murine leukemia virus (PIM)-1 were examined by in situ hybridization, immunohistochemical analysis, and immunofluorescence in labial salivary glands (LSGs) obtained from 16 patients with SS and five controls. The microcell count method has been applied to calculate the NFATc1-positive area/infiltrating cell area in LSGs, and we compared those results to the infiltrating cell area, focus score, serum immunoglobulin G, and the European League Against Rheumatism Sjögren’s Syndrome Disease Activity Index. The NRON expression in the nuclei of cell-infiltration lesions of the SS patients were prominent. The NFATc1 expression was strong in the cytoplasm of infiltrating mononuclear cells and weak in ducts of both SS and controls. In SS, the NFATc1-positive area/infiltrating cell area was positively correlated with the infiltrating cell area and focus score. CD3/CD4 was expressed in infiltrating mononuclear cells, and PIM-1 colocalized with NFATc1 in the cytoplasm. These results suggest NRON along with NFATc1/PIM-1 in SS LSGs might participate in SS pathophysiology.