The Accuracy of Electrical Impedance Tomography for Breast Cancer Detection: A Systematic Review and Meta-Analysis

Introduction. Incidence of breast cancer (BC) in 2020 is about 2.26 million new cases. It is the first common cancer accounting for 11.7% of all cancer worldwide. Disease complications and the mortality rate of breast cancer are highly dependent on the early diagnosis. Therefore, novel human breast-imaging techniques play an important role in minimizing the breast cancer morbidity and mortality rate. Electrical impedance tomography (EIT) is a noninvasive technique to image the breast using the electrical impedance behavior of the body tissues. Objectives. The aims of this manuscript are as follows: (1) a comprehensive investigation of the accuracy of EIT for breast cancer diagnosis through searching pieces of evidence in the valid databases and (2) meta-analyses of the results. Methods. The systematic search was performed in the electronic databases including PubMed, Web of Science, EMBASE, Science Direct, ProQuest, Scopus, and Google Scholar without time and language limitation until January 2021. Search terms were “EIT” and “Breast Cancer” with their synonyms. Relevant studies were included based on PRISMA and study objectives. Quality of studies and risk of bias were performed by QUADAS-2 tools. Then, relevant data were extracted in Excel form. The hierarchical/bivariate meta-analysis was performed with “metandi” package for the ROC plot of sensitivity and specificity. Forest plot of the Accuracy index and double arcsine transformations was applied to stabilize the variance. The heterogeneity of the studies was evaluated by the forest plots, χ2 test (assuming a significance at the a-level of 10%), and the I2 statistic for the Accuracy index. Results. A total of 4027 articles were found. Finally, 12 of which met our criteria. Overall, these articles included studies of 5487 breast cancer patients. EIT had an overall pooled sensitivity and specificity of 75.88% (95% CI, 61.92% to 85.89%) and 82.04% (95% CI, 69.72% to 90.06%), respectively. The pooled diagnostic odds ratio was 14.37 (95% CI, 6.22% to 33.20%), and the pooled effect of accuracy was 0.79 with 95% CI (0.73, 0.83). Conclusions. This study showed that EIT can be used as a useful method alongside mammography. EIT sensitivity could not be compared with the sensitivity of MRI, but in terms of specificity, it can be considered as a new method that probably can get more attention. Furthermore, large-scale studies will be needed to support the evidence

Development of the Breast Surgical Oncology Fellowship in the United States

The surgical treatment of breast cancer has rapidly evolved over the past 50 years, progressing from Halsted’s radical mastectomy to a public campaign of surgical options, aesthetic reconstruction, and patient empowerment. Sparked by the research of Dr. Bernard Fisher and the first National Surgical Adjuvant Breast and Bowel Project trial in 1971, the field of breast surgery underwent significant growth over the next several decades, enabling general surgeons to limit their practices to the breast. High surgical volumes eventually led to the development of the first formal breast surgical oncology fellowship in a large community-based hospital at Baylor University Medical Center in 1982. The establishment of the American Society of Breast Surgeons, as well as several landmark clinical trials and public campaign efforts, further contributed to the advancement of breast surgery. In 2003, the Society of Surgical Oncology (SSO), in partnership with the American Society of Breast Surgeons and the American Society of Breast Disease, approved its first fellowship training program in breast surgical oncology. Since that time, the number of American fellowship programs has increased to approximately 60 programs, focusing not only on training in breast surgery, but also in medical oncology, radiation oncology, pathology, breast imaging, and plastic and reconstructive surgery. This article focuses on the happenings in the United States that led to the transition of breast surgery from a subset of general surgery to its own specialized field. 1. Introduction: The Breast Surgery Movement Breast cancer awareness has become a social and cultural movement. Individuals worldwide understand the meaning of the “pink ribbon” as a symbol of support for breast cancer and its patients, survivors, and research. This international recognition is appropriate, as breast cancer is the world’s most prevalent cancer. At the end of 2020, there were 7.8 million women alive who were diagnosed with breast cancer in the last five years. [1] The treatment of breast cancer has radically changed over the past several decades, leading to the development of breast surgery as a surgical specialty. As only 50 years have passed since the first National Surgical Adjuvant Breast and Bowel Project (NSABP) clinical trial in 1971, it is fruitful to analyze the contributions and historical happenings that have led to the development of breast surgery as a specialty. 2. 1970-1971: Dr. Bernard Fisher’s Surgical Dilemma and Landmark Trial Prior to 1970, the “Halstedian Hypothesis” governed the way that physicians thought about cancer and metastasis. This paradigm proposed an orderly spread from local to distant sites [2]. However, even after a “radical” resection of skin, breast, muscle, and lymphatics, patients succumbed to widespread breast cancer. It was at this time that Dr. Bernard Fisher from the University of Pittsburgh published a critique entitled “The Surgical Dilemma in the Primary Therapy of Invasive Breast Cancer: A Critical Appraisal” (Figure 1)

The Prognosis and Predictive Value of Estrogen Negative/Progesterone Positive (ER−/PR+) Phenotype: Experience of 1159 Primary Breast Cancer from a Single Institute

Breast cancer is a serious worldwide public health problem and is currently the most common cancer overall. Its endocrine therapy is related to the expression of the steroid hormones, estrogen receptor (ER), and progesterone receptor (PR). Breast cancers can be presented under multiple profiles of steroid hormones: ER(−)/PR(+), ER(+)/PR(−), double-positive/negative ER, and PR. 2–8% of all breast cancers express only PR (ER−/PR+) which is an abnormal phenotype, with less known about their behaviors and outcomes. Our study was performed on a large and well-characterized database of primary breast cancer from 2012 to 2019, up to 1159 cases. These cases were divided according to ER and PR expression, as we put all of our focus on ER-negative/PR-positive group, more specifically ER−/PR+/HER2+ and ER−/PR+/HER2− gene expressions, to highlight their features and find a pattern that links HR (hormone receptors) profiles and breast cancer subtypes. Out of the informative cases, 94 patients (8%) had ER−/PR+ breast cancers, while 676 (58.4%) had ER+/PR+, 88 (7.6%) had ER+/PR−, and 164 (14.2%) had ER−/PR− tumors. The ER−/PR+ group was statistically correlated with a high risk of recurrence and death in midway between the double-negative and double-positive HR. According to HER2 status, a low DFS was observed in patients ER−/PR+/HER2−, which is closer to the DFS of TNBC cases but worse than ER+/PR any. On the other side, the ER−/PR+/HER2+ showed also a poorer DFS closer to the HER2+ subgroup in between TNBC and ER+/PR any. The clinicopathological features of the ER−/PR+/HER2− and ER−/PR+ HER2+ have distinguished the patients into two groups with a difference in some clinicopathological characteristics: both groups had closer OS estimation, which was worse than ER−/PR any and better than TNBC and HER2. The ER−/PR+/HER2− seems to increase the risk of recurrence than ER−/PR+/HER2+ when compared to ER+/PR any. On the other hand, the ER−/PR+/HER2+ seems to increase the risk of death more than ER−/PR+/HER2− in comparison with ER+/PR any. Our results support that ER−/PR+ tumors really exist and are rare and clinically and biologically distinct subtypes of breast cancer. In addition, our analysis, which was based on dividing the groups according to HER2 expression, has revealed the existence of two distinct groups; this gave the ER−/PR+ subgroup a heterogeneity characterization. Moreover, this breast cancer subtype should not be treated as a luminal tumor but rather according to the HER2 expression status. 1. Introduction Breast cancer is a serious worldwide public health problem and is currently the most common cancer overall [1], causing the highest number of cancer-related deaths among women. Due to its complexity and heterogeneity, breast cancer presents veritable variation in clinical, morphological, and molecular management [2]. The molecular classification by immunohistochemical expression of estrogen receptor ER, progesterone receptor PR, human epidermal growth factor receptor 2 (HER2), and proliferation index Ki-67 established by St. Gallen surrogate for breast cancer subtypes reveals five main entities: luminal-A, luminal-B HER2-negative, luminal B HER2-positive, HER2 enriched, and TNBC (triple negative: lack of expression of ER, PR, and no overexpression of HER2) [3, 4]. Breast cancer endocrine therapy is actually related to the expression of the steroid hormones, estrogen receptor (ER), and progesterone receptor (PR). The estrogen receptor (ER) and progesterone receptor (PR) are expressed in more than 75% of breast cancers [5, 6]. They are one of the most powerful prognostic factors and predictive markers in hormonal treatment [7–9]. Therefore, breast cancers can be presented in multiple profiles of steroid hormones: ER(−)/PR(+), ER(+)/PR(−), double-positive/negative ER, and PR [3]. The treatment strategies decisions in cases of double-positive/negative steroid hormones can be taken easily [9]. Not to mention, hormone-receptor-positive breast tumors are qualified by less aggressive clinicopathological outcomes and a high prognosis in reason of the benefits from endocrine therapy [10]. Estrogen receptors (ER) status on its own is useful in predicting benefits from antiestrogenic treatment, but not from hormonal treatment. Thus, progesterone receptors are often tested in parallel with estrogen receptors, as studies have shown that PR expression is conditional on ER activity [3, 4, 11, 12]. Consequently, the luminal tumors are the most common breast cancer phenotypes, presenting more than 50% of all breast cancers [9]. Moreover, only 15–20% of all breast cancer cases have expressed one hormone receptor at a time, with a predominance of tumors expressing ER, but not PR (ER+/PR−) [13, 14]. The existence of breast cancer with ER-negative/PR-positive phenotype is still debated. The biological significance, prognosis, and predictive impact of ER−/PR+ breast cancers have been discussed; there are some hypotheses about considering this profile as a technical artifact. The HR status of breast cancer may be altered due to several factors, resulting in a false-negative ER and/or false-positive PR assay. Antibody selection for ER testing, improper tissue fixations, and different thresholds for reporting immunostaining or less sensitive immunohistochemistry, are some of these factors [15–17]. The American Society of Clinical Oncology/College of American Pathologists recommended that ER−/PR+ tumors should be tested repeatedly to avoid false negative ER results [7, 18]

Safety of Vaccines against SARS-CoV-2 among Polish Patients with Multiple Sclerosis Treated with Disease-Modifying Therapies

(1) Background: The present study aims to report the side effects of vaccination against coronavirus disease 2019 (COVID-19) among patients with multiple sclerosis (MS) who were being treated with disease-modifying therapies (DMTs) in Poland. (2) Methods: The study included 2261 patients with MS who were being treated with DMTs, and who were vaccinated against COVID-19 in 16 Polish MS centers. The data collected were demographic information, specific MS characteristics, current DMTs, type of vaccine, side effects after vaccination, time of side-effect symptom onset and resolution, applied treatment, relapse occurrence, and incidence of COVID-19 after vaccination. The results were presented using maximum likelihood estimates of the odds ratio, t-test, Pearson’s chi-squared test, Fisher’s exact p, and logistic regression. The statistical analyses were performed using STATA 15 software. (3) Of the 2261 sampled patients, 1862 (82.4%) were vaccinated with nucleoside-modified messenger RNA (mRNA) vaccines. Mild symptoms after immunization, often after the first dose, were reported in 70.6% of individuals. Symptoms included arm pain (47.5% after the first dose and 38.7% after the second dose), fever/chills/flu-like symptoms (17.1% after the first dose and 20.5% after the second dose), and fatigue (10.3% after the first dose and 11.3% after the second dose). Only one individual presented with severe side effects (pro-thrombotic complications) after vaccination. None of the DMTs in the presented cohort were predisposed to the development of side effects. Nine patients (0.4%) had a SARS-CoV-2 infection confirmed despite vaccination. (4) Conclusions: Vaccination against SARS-CoV-2 is safe for people with MS who are being treated with DMTs. Most adverse events following vaccination are mild and the acute relapse incidence is lo

The Existence of at Least Three Genomic Signature Patterns and at Least Seven Subtypes of COVID-19 and the End of the Disease

Hoping to find genomic clues linked to COVID-19 and end the pandemic has driven scientists’ tremendous efforts to try all kinds of research. Signs of progress have been achieved but are still limited. This paper intends to prove the existence of at least three genomic signature patterns and at least seven subtypes of COVID-19 driven by five critical genes (the smallest subset of genes) using three blood-sampled datasets. These signatures and subtypes provide crucial genomic information in COVID-19 diagnosis (including ICU patients), research focuses, and treatment methods. Unlike existing approaches focused on gene fold-changes and pathways, gene-gene nonlinear and competing interactions are the driving forces in finding the signature patterns and subtypes. Furthermore, the method leads to high accuracy with hospitalized patients, showing biological and mathematical equivalences between COVID-19 status and the signature patterns and a methodological advantage over other methods that cannot lead to high accuracy. As a result, as new biomarkers, the new findings and genomic clues can be much more informative than other findings for interpreting biological mechanisms, developing the second (third) generation of vaccines, antiviral drugs, and treatment methods, and eventually bringing new hopes of an end to the pandemic

Epitope Profiling of Diphtheria Toxoid Provides Enhanced Monitoring for Consistency Testing during Manufacturing Process Changes

In the vaccine industry, multiple physicochemical, immunological, in vitro and in vivo analytical methods are applied throughout the manufacturing process to characterize and monitor the quality of vaccines. Presented here is the Single Epitope Antigenicity Test (SEAT), an innovative, quantitative epitope profiling method which provides an extended immunochemical analysis for diphtheria toxoid (DTxd) to be used for consistency testing during manufacturing process changes. The method uses BioLayer Interferometry (BLI) and a panel of monoclonal antibodies (mAbs) to independently assess nine individual antigenic sites of DTxd. The panel includes mAbs which are functional, bind distinct sites on DTxd and are able to distinguish intact DTxd from that which has been exposed to heat treatment. The SEAT method was qualified for precision, accuracy, and linearity, and was used to define a preliminary comparability range for DTxd made using the current manufacturing process. DTxd lots manufactured using alternate processes were assessed in the context of this range to determine the impact on DTxd antigenicity. Epitope profiling by SEAT provides quantitative information on the integrity of multiple important antigenic regions of DTxd, and therefore represents a valuable tool in a comprehensive analytical test package which can be used to support manufacturing process changes for vaccine

Prevalence, Severity, and Predictors of Poststroke Depression in a Prospective Cohort of Jordanian Patients

Poststroke depression (PSD) is common and remains a significant risk factor for poor outcomes. This prospective study is aimed at assessing the prevalence, severity, and predictors of PSD among Jordanian stroke survivors. A total of 151 patients who were consequently admitted to a tertiary teaching hospital with ischemic or hemorrhagic strokes were enrolled. Participants were screened on admission for premorbid depression using the PHQ-9 questionnaire; then, screening for PSD was repeated one and three months after stroke using the same tool. Depression prevalence at each screening was reported, and logistic regression analysis was conducted to evaluate for significant predictors. PHQ-9 scores suggestive of depression were reported by 15%, 24.83%, and 17.39% of respondents on admission and after one and three months, respectively. Scores suggesting severe depression were reported by 0.71%, 2.13%, and 6.52% of respondents, respectively. Significant predictors of PSD were having chronic kidney disease, current smoking status, moderate or severe disability (mRS score) at stroke onset, and severe dependence (BI) after one month ( values 0.007, 0,002, 0.014, and 0.031, respectively). Patients with secondary and high school education levels were less likely to get depression compared with illiterate patients ( 0.042). This study showed that nearly one in four Jordanian stroke survivors experienced PSD after one month. In contrast, while the overall PSD prevalence declined towards the end of follow-up period, patients who remained depressed showed a tendency towards higher PSD severity. 1. Introduction Stroke is a significant cause of morbidity and mortality globally [1]. It is the second leading noncommunicable cause of death in Jordan and a considerable source of complications and physical disability [2, 3]. Stroke survivors are liable to a multitude of physical, psychiatric, social, and functional impacts. Poststroke depression (PSD) is the most frequent and a very important neuropsychiatric complication. Stroke survivors who develop PSD are at a greater risk of poor functional outcomes, lower quality of life, increasing cognitive impairment, recurrent vascular events, and higher mortality than those without depression [4–6]. The DSM-V defines poststroke mood disorders as mood disorders due to stroke, with the specifiers of depressive features, major depressive-like episode, or mixed mood features [6]. Studies evaluating PSD have reported varying findings owing to heterogeneous settings, populations, and methodologies. Also, several studies suggested that PSD prevalence differs with the time interval between stroke and depression assessment [7]. Additionally, some neurological symptoms such as aphasia and cognitive impairment may conceal mood abnormalities, and there is a lack of consensus over the best screening tool for case-finding [7, 8]. Subsequently, the range of estimated PSD prevalence is wide [9, 10]. However, meta-analyses with large databases reported that approximately one-third of survivors developed PSD at any time point up to 5 years following stroke [11–13]. Surveys from the Middle East and North Africa (MENA) region also reported a wide prevalence of PSD (17-73%) [10], while previous surveys from Jordan reported a range from 25% to 76% [14–17]. Studies aiming to identify risk factors predisposing to PSD have also been inconsistent. The most frequently identified risk factors include the level of physical disability, stroke severity, and history of mental illness [7, 18]. Different instruments have been used to screen stroke survivors for PSD [19]. The Patient Health Questionnaire-9 (PHQ-9) is a self-administered tool that employs nine standard questions to score each of the nine DSM criteria as zero (not at all) to three (nearly every day) [20]. It has been well-validated in different settings as a brief screener for PSD [19, 21, 22]. A meta-analysis found that PHQ-9 had a summary sensitivity of 0.77 and a specificity of 0.94 (0.90–0.97) [23]. Cut-off PHQ-9 scores of 5, 10, 15, and 20 represent mild, moderate, moderately severe, and severe depression, respectively [20]. This study is aimed at determining the prevalence and severity of PSD at one and three months after stroke and at investigating PSD predictors among Jordanian stroke survivors

Daytime Sleepiness among Medical Colleges’ Students in Jordan: Impact on Academic Performance

ntroduction. Sleep disorders are extremely prevalent in the general population. College students are more susceptible to sleep problems. This is due to the increased competition in getting a job position and the current alterations in the labor market. Poor sleep is prevalent and has deleterious effects on college students, but its frequency among college students has not been documented in Jordan. So, the aims of this study are to assess the prevalence of daytime sleepiness among medical college students in Jordan and to look for any links between daytime sleepiness and academic performance. Methods. A cross-sectional study performed on medical and paramedical specialties students and Epworth sleepiness Sscale (ESS) was used. To assess the students’ academic performance, the cumulative grade point average was utilized. Results. 977 students from five medical colleges participated in the study. ESS scores were abnormal in 34.4% of students and were considered to have daytime sleepiness. Significant lower ESS scores were associated with students who reported good sleep quality than students who reported poor sleep quality. Significant lower ESS scores were reported by students who slept more than 7 hours compared with students who slept less than 6 hours. The ESS scores were not significantly associated with students’ CPGA. Conclusion. Daytime sleepiness is highly prevalent among medical students in Jordan. The data of this study might be very helpful to assess the academic policy makers to develop intervention strategies that resolve the sleep disturbances in college students and reduce its impact on the academic achievements

Most common reasons for primary care visits in low- and middle-income countries: A systematic review

With the Covid-19 pandemic and the introduction of the WHO’s Essential Diagnostics List (EDL), increasing global attention is focused on the crucial role of diagnostics in achieving universal health coverage. To create national EDLs and to aid health system planning, it is vital to understand the most common conditions with which people present at primary care health facilities. We undertook a systematic review of the most common reasons for primary care visits in low- and middle-income countries. Six databases were searched for articles published between January 2009 and December 2019, with the search updated on MEDLINE to January 2021. Data on the most common patient reasons for encounter (RFEs) and provider diagnoses were collected. 17 of 22,279 screened articles were included. Most studies used unvalidated diagnostic classification systems or presented provider diagnosis data grouped by organ system, rather than presenting specific diagnoses. No studies included data from low-income countries. Only four studies (from Brazil, India, Nigeria and South Africa) using the ICPC-2 classification system contained RFE and provider diagnosis data and could be pooled. The top five RFEs from the four studies were headache, fever, back or low back symptom, cough and pain general/multiple sites. The top five diagnoses were uncomplicated hypertension, upper respiratory tract infection, type 2 diabetes, malaria and health maintenance/prevention. No psychological symptoms were among the top 10 pooled RFEs. There was more variation in top diagnoses between studies than top RFEs, showing the importance of creating location-specific lists of essential diagnostics for primary care. Future studies should aim to sample primary care facilities from across their country of study and use ICPC-3 to report both patient RFEs and provider diagnoses

Revision Surgery Using Retrograde Nail versus Replating in Nonunion Distal Femur Fracture Treated with Plate

Articular distal femur fractures represent 4% to 6% of femur fractures. Locking compression plates (LCPs) are the main treatment option. Nevertheless, a reoperation rate of 12.9% has been reported; nonunion is reported at 4.8%, delayed union at 1.6%, and malunion at 0.6%. Treatment of nonunions can be challenging as no unanimous consensus regarding the best surgical technique has been reached. The aim of this study was to evaluate and compare two types of revision surgery as treatment of LCP-treated articular distal femoral fracture nonunion: retrograde nail or replating. A retrospective cohort study of patients admitted from January 2015 to February 2017 for nonunion of AO/OTA 33C2 fractures previously treated with a lateral LCP was conducted. Patients were treated either with intramedullary nailing (Group A) or with replating (Group B). One independent observer performed clinically and radiographically followed up at 1, 3, 6, 9, 12, 24, and 36 months after surgery. The nonunion scoring system (NUSS) was used. Nine patients were included in our study. The mean follow-up was 2 years. Five patients were treated with intramedullary nailing and four with replating. The NUSS score was 24.2 ± 6.8 in the nailing group and 37.3 ± 3 in the replating group (). In the nailing group, radiographic consolidation was obtained in all cases. In the replating group, nonunion was found in 3 patients and failure of osteosynthesis in one patient. Therefore, four patients (Group B) underwent implant removal and retrograde femoral nailing, obtaining radiological healing. The union time was 7.6 months in the nailing group. Retrograde intramedullary nailing can be used as an effective treatment of aseptic AO-33C distal femoral nonunion following primary locking plating