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[Background]: Homozygous familial hypercholesterolaemia (HoFH) is a rare inherited disorder resulting in extremely elevated low-density lipoprotein cholesterol levels and premature atherosclerotic cardiovascular disease (ASCVD). Current guidance about its management and prognosis stems from small studies, mostly from high-income countries. The objective of this study was to assess the clinical and genetic characteristics, as well as the impact, of current practice on health outcomes of HoFH patients globally., [Methods]: The HoFH International Clinical Collaborators registry collected data on patients with a clinical, or genetic, or both, diagnosis of HoFH using a retrospective cohort study design. This trial is registered with ClinicalTrials.gov, NCT04815005., [Findings]: Overall, 751 patients from 38 countries were included, with 565 (75%) reporting biallelic pathogenic variants. The median age of diagnosis was 12∙0 years (IQR 5∙5–27∙0) years. Of the 751 patients, 389 (52%) were female and 362 (48%) were male. Race was reported for 527 patients; 338 (64%) patients were White, 121 (23%) were Asian, and 68 (13%) were Black or mixed race. The major manifestations of ASCVD or aortic stenosis were already present in 65 (9%) of patients at diagnosis of HoFH. Globally, pretreatment LDL cholesterol levels were 14∙7 mmol/L (IQR 11∙6–18∙4). Among patients with detailed therapeutic information, 491 (92%) of 534 received statins, 342 (64%) of 534 received ezetimibe, and 243 (39%) of 621 received lipoprotein apheresis. On-treatment LDL cholesterol levels were lower in high-income countries (3∙93 mmol/L, IQR 2∙6–5∙8) versus non-highincome countries (9∙3 mmol/L, 6∙7–12∙7), with greater use of three or more lipid-lowering therapies (LLT; highincome 66% vs non-high-income 24%) and consequently more patients attaining guideline-recommended LDL cholesterol goals (high-income 21% vs non-high-income 3%). A first major adverse cardiovascular event occurred a decade earlier in non-high-income countries, at a median age of 24∙5 years (IQR 17∙0–34∙5) versus 37∙0 years (29∙0–49∙0) in high-income countries (adjusted hazard ratio 1∙64, 95% CI 1∙13–2∙38)., [Interpretation]: Worldwide, patients with HoFH are diagnosed too late, undertreated, and at high premature ASCVD risk. Greater use of multi-LLT regimens is associated with lower LDL cholesterol levels and better outcomes. Significant global disparities exist in treatment regimens, control of LDL cholesterol levels, and cardiovascular event-free survival, which demands a critical re-evaluation of global health policy to reduce inequalities and improve outcomes for all patients with HoFH., Amsterdam University Medical Centers, Location Academic Medical Center; Perelman School of Medicine at the University of Pennsylvania; and European Atherosclerosis Society

The current study was designed to compare oncological outcomes between oncoplastic (OBCS) and conventional breast-conserving surgery (BCS). Data collected retrospectively from two groups of patients diagnosed with breast cancer, cases group (OBCS) and control group (BCS), were analyzed. A total of 277 women were included in the analysis: 193 (69.7%) in the cases group and 84 (30.3%) in the control group. Resected volume was larger in the OBCS group (438.05 ± 302.26 cm3 vs 223.34 ± 161.75 cm3; p

To illustrate the effectiveness of hysteroscopic endometrial resection in conservative treatment of early endometrial cancer/atypical hyperplasia in women of reproductive age. Review of outcomes of women of reproductive age who underwent fertility sparing treatment (hysteroscopic superficial endometrectomy followed by progestin therapy) in early endometrial cancer. Eight women with Stage I endometrial cancer and three with atypical endometrial hyperplasia underwent hysteroscopic superficial endometrial resection, followed by 1-year treatment with oral megestrol acetate. One patient had a synchronous endometrioid ovarian carcinoma. One patient with Grade 2 carcinoma opted for conservative treatment and had hysterectomy 3 months later for persisting disease. Ten patients showed no evidence of residual disease during a 12-month follow-up period with regular hysteroscopy. Five patients had seven pregnancies without assisted reproductive technology. One patient got pregnant after one attempt of in-vitro fertilization and oocyte donation. Pregnancy rate was 54.5%; two patients had two successful pregnancies and deliveries. Average time to pregnancy was 16 months from the end of treatment. All babies were delivered vaginally. Total superficial endometrial resection followed by progestin can be considered in patients with early endometrial cancer/atypical hyperplasia who still want to conceive. It does not seem to impair fertility nor pregnancy outcomes in women of reproductive age.

We present the case of a 30-year-old lady who underwent a core needle biopsy for a BIRADS 4 lesion of her left breast and was diagnosed as having a cellular fibroadenoma. The final diagnosis after excision returned to be a periductal stromal tumor (PST). An extremely rare entity, the PST is actually classified as a subtype of phyllodes tumor, with specific criteria that are only found upon histological examination of the specimen. Care should be taken when considering the diagnosis of fibroadenoma based only on clinical, radiological, and biopsy findings. Any nonclassical, clinical, or radiological findings should prompt a wide excision. Prognosis is generally good when clear margins are obtained and in the absence of malignant heterologous elements.

Organoids represent one of the most important advancements in the field of stem cells during the past decade. They are three-dimensional in vitro culturing models that originate from self-organizing stem cells and can mimic the in vivo structural and functional specificities of body organs. Organoids have been established from multiple adult tissues as well as pluripotent stem cells and have recently become a powerful tool for studying development and diseases in vitro, drug screening, and host–microbe interaction. The use of stem cells—that have self-renewal capacity to proliferate and differentiate into specialized cell types—for organoids culturing represents a major advancement in biomedical research. Indeed, this new technology has a great potential to be used in a multitude of fields, including cancer research, hereditary and infectious diseases. Nevertheless, organoid culturing is still rife with many challenges, not limited to being costly and time consuming, having variable rates of efficiency in generation and maintenance, genetic stability, and clinical applications. In this review, we aim to provide a synopsis of pluripotent stem cell-derived organoids and their use for disease modeling and other clinical applications.

Breast conservation rate is being increasingly used nowadays as a marker of breast cancer care among hospitals. Searching for the ideal technique to predict the feasibility of BCS is ongoing. For this matter, the preoperative MRIs of 169 patients operated with radical or conservative surgery were reviewed. We estimated the tumor volume (TV) and breast volume (BV) on enhanced 3D-MRI and compared the tumor-to-breast volume ratio (TV/BV) in both groups. The mean ratio was 9.5% in the mastectomy group and 1.7% in the BCS group. A tumor-to-breast volume ratio less than 4% seemed to favor the adoption of a conservative option. Our data suggest that preoperative 3D-MRI can orient the surgical approach by assessing the TV/BV ratio, increasing lumpectomy rates with clear margins and good cosmetic outcome.

Aim: To describe the activity in the ‘breast unit’ at the department of radiology during the coronavirus disease 19 lockdown in a university hospital treating coronovirus disease 19 patients in a Middle-Eastern developing country. Materials: This was a retrospective study conducted from March 9 until 11 May 2020, in the breast unit at the department of radiology of a central university hospital in a Middle-Eastern developing country. Data were collected from 205 patients visiting the breast unit during the lockdown period and compared with the activity in the same period in the previous year. Results: Reduction of the breast unit activity was estimated at 73%. In addition, 153 mammograms, 205 ultrasounds, and 16 breast MRIs were done. Indications for mammogram were screening (41.5%), follow-up (22%), clinical symptoms (20%) and breast cancer surveillance (16.5%). MRI was performed mostly for preoperative surgical management. The rate of positive biopsies was 41%. All staff members and patients have accommodated to new adjustments. Conclusion: Activity in the breast unit dropped during the lockdown period. Staff should continue to seek their own and their patient’s safety without diminishing the quality of healthcare.

To evaluate the diagnostic value of diffusion-weighted imaging (DWI) in combination with conventional MRI in predicting metastatic axillary lymph nodes (ALN) in breast cancer (BC). We reviewed pathological findings and clinical breast MRI examinations of 169 patients with invasive BC who were evaluated at the Hotel-Dieu de France Hospital in 2009-2015. Morphological parameters and apparent diffusion coefficient (ADC) value were compared with pathological nodal status. Independent t-test/chi-square test and a Pearson correlation analysis were used. With pathological diagnosis as reference, MRI-based interpretations were 87.5% specific and 70.3% sensitive. On conventional MRI, the round shape of lymph nodes (LNs), loss of fatty hilum, irregular margins and hypo-intensity/heterogeneous intensity on T2-weighted sequence were statistically significantly different between metastatic and nonmetastatic groups (P < .001, each). Mean size of metastatic ALN was larger compared with negative ALN (13.9 mm vs. 10.9 mm, P < .001). LNs ≥ 12 mm were associated with higher risk of metastasis (P < .001). ADC value was not significantly different between both groups (P = .862). Conventional MRI using the ALN shape, signal intensity in T2-weighted sequences, loss of fatty hilum, regularity of the margins and size of the LNs can evaluate the axilla with high specificity. ADC value could not be used as a reliable parameter.

Background Placenta percreta is associated with high hemorrhagic risk and can be complicated with fatal thromboembolic events. Involving a multidisciplinary team in the treatment of these patients is mandatory to reduce morbidity and mortality. Case presentation This paper reports the case of a 22-year-old patient with placenta percreta who was referred to our tertiary care center for delivery. Few hours after undergoing a successful cesarean hysterectomy, the patient developed a pulmonary embolism and cardiac arrest. A transthoracic echocardiogram done in the intensive care unit (ICU) showed a thrombus in the right ventricle. After cardiac resuscitation, the patient underwent an urgent thoracotomy and a pulmonary artery thrombectomy; many clots were retrieved from the pulmonary artery. After weaning from extracorporeal circulation, an intraoperative transesophageal cardiac ultrasound enabled the medical team to detect a new free-floating thrombus in the right atrium and right ventricle, and consequently to perform an embolectomy and prevent the patient’s death. Conclusion This case emphasizes the role of multidisciplinary team in treating high-risk obstetric cases that could be complicated with massive and fatal thromboembolic events. The use of intraoperative transthoracic echocardiography helps in detecting a new thrombus and guides the anesthesiologist in the intra-operative monitoring.

Prostate cancer (PCa) is the second most common cancer in men. Common treatments include active surveillance, surgery, or radiation. Androgen deprivation therapy and chemotherapy are usually reserved for advanced disease or biochemical recurrence, such as castration-resistant prostate cancer (CRPC), but they are not considered curative because PCa cells eventually develop drug resistance. The latter is achieved through various cellular mechanisms that ultimately circumvent the pharmaceutical’s mode of action. The need for novel therapeutic approaches is necessary under these circumstances. An alternative way to treat PCa is by repurposing of existing drugs that were initially intended for other conditions. By extrapolating the effects of previously approved drugs to the intracellular processes of PCa, treatment options will expand. In addition, drug repurposing is cost-effective and efficient because it utilizes drugs that have already demonstrated safety and efficacy. This review catalogues the drugs that can be repurposed for PCa in preclinical studies as well as clinical trials.

Uvod: I přes velký pokrok v nedavne době je familiarni hypercholesterolemie (FH) stale jestě celosvětově podceňovane, nedostatecně diagnostikovane, a tedy i nedostatecně lecene onemocněni. O přesne prevalenci pacientů postižených familiarni hypercholesterolemii v regionu středni, východni a jižni Evropy (CESE) mame jen velmi malo informaci. Cilem studie bylo popsat na zakladě dostupných udajů epidemiologickou situaci v regionu CESE. Metody: Vsichni vedouci představitele projektu ScreenPro FH v jednotlivých oblastech byli požadani o poskytnuti lokalnich udajů, ktere se týkaji (a) expertniho odhadu prevalence FH, (b) již fungujicich zdravotnických zařizeni, (c) použitých diagnostických kriterii, (d) poctu pacientů již zavedených v mistni databazi a konecně (e) dostupnosti možnosti lecby (zejmena plazmaferezy). Výsledky: Vzhledem k odhadovane prevalenci FH přibližně 1 : 500 odhadujeme, že celkova populace FH heterozygotů v regionu CESE zahrnuje 588 363 osob. V mistnich databazich se vsak zobrazilo pouze 14 108 osob (2,4 %), přicemž mira zobrazeni se lisila v rozmezi od 0,1 % až 31,6 %. Pouze 4 země oznamily dostupnost LDL aferezy. Zavěr: Nase udaje svědci o velke populaci pacientů postižených heterozygotni formou FH v regionu CESE a zaroveň o nizkých podilech jejich zobrazeni. V ramci projektu ScreenPro FH jsou vsak nyni vytvařeny potřebne struktury a můžeme tak doufat v dosaženi přiznivějsich výsledků.

Objectives: Surveys of the general population regarding sex selection using pre-implantation genetic diagnosis are limited and were mainly conducted in the United States and Northern Europe. In those Western societies, surveys have shown that people’s interest in using sex selection techniques is encouraged by the desire for a sexually balanced family. It is important to determine attitudes to sex selection in a wider range of countries especially that cultural differences exist among countries. Study design: A questionnaire-based cross-sectional study regarding attitudes towards sex selection for non-medical reasons was designed. One thousand five hundred participants of the reproductive age group presenting to the Women s Health Center at the American University of Beirut Medical Center were offered to complete the survey. The questionnaire included demographic details, obstetric and infertility history, opinions regarding sex selection, personal interest in expanding the family, and personal interest in choosing the sex of a future child. Results: The response rate was 86.6%. Nineteen per cent of the respondents considered it strictly prohibited, 38.8% considered the technique acceptable only if medically indicated while 33.4% believed that it should be available to all those who request it. Multivariate logistic regression on the predictors of the variable affecting the attitudes towards sex selection showed that the educational level, religious disapproval and the desire of the opposite sex of the already existing children were the only significant predictors. Conclusion: The middle-eastern multi-religious population studied has a negative attitude towards sex selection through pre-implantation genetic diagnosis. Religion, educational status and desire of children of both genders were identified as the significant predictors of the decision whether to accept sex selection or not. Keywords: Surveys and questionnaires, Sex preselection, Attitude, Humans

Background Clinical trials conducted in Lebanon are increasing. However, little is known about the performance of research ethics committees (RECs) in charge of reviewing the research protocols. This study aimed to assess the level of adherence to the ethics surrounding the conduct of clinical trials and perceptions of team members regarding roles of the RECs during the conduct of clinical trials in Lebanon. The research question was: Are RECs adherent to the ethics surrounding the conduct of clinical trials (chapters II and IV in ‘Standards and Operational Guidance for Ethics Review of Health-related Research with Human Participants’ in Lebanon?’ Methods This was a quantitative and descriptive questionnaire-based study conducted among RECs of university hospitals in Lebanon. The questionnaire had to be completed online and included general questions in addition to items reflecting the different aspects of a REC performance and effectiveness. All the questionnaire was assigned a total score of 175 points. General information and questions assigned point values/scores were analysed using descriptive statistics: frequency and percentage, mean score ± standard deviation. Results Ten RECs participated in the study (52 persons: four chairs, one vice-president, 47 ordinary members). Forty-seven (90.4%) had previous experience with clinical research and 30 (57.7%) had a diploma or had done a training in research ethics. Forty-one percent confirmed that they were required to have a training in research ethics. All RECs had a policy for disclosing and managing potential conflicts of interest for its members, but 71.8% of participants reported the existence of such a policy for researchers. Thirty-three point three percent reported that the RECs had an anti-bribery policy. The questionnaire mean score was 129.6 ± 22.3/175 points reflecting thus an excellent adherence to international standards. Conclusion Inadequate training of REC members and the lack of anti-bribery policies should be resolved to improve their performance. Electronic supplementary material The online version of this article (doi:10.1186/s13063-017-2397-2) contains supplementary material, which is available to authorized users.

Objective To report the outcomes of women with placenta percreta who were surgically treated by a specialized technique based on gynecologic oncology experience, and to demonstrate its safety in preventing ureteral lesions and reducing blood loss. Methods In the present retrospective study, data from patients with placenta percreta radically treated at Hotel-Dieu de France, Beirut, Lebanon, between December 2012 and January 2017 were reviewed. Demographic, pathology, and delivery data, medical history, per-operative and postoperative information, and neonatal data were assessed. Operative and postoperative outcomes were compared between emergency and scheduled cases. Results Data from 35 patients were reviewed. Median gestational age at delivery was 34 weeks. Cesarean hysterectomy was scheduled in 20 (60%) cases. No ureteral lesions were noted. The median estimated blood loss was 1 L and a median of 3 units of red blood cells units was transfused. Emergency and scheduled cases presented comparable estimated blood loss, intra-operative transfusion, bladder injury incidence, and surgery duration (all P>0.05). The mean delivery weight was 2100 g; admission to the neonatal intensive care unit was needed for 30 (86%) neonates. Conclusion The surgical technique developed for placenta percreta was found to be effective (operative and postoperative outcomes) and safe (prevention of ureteral lesions).

Intima-media thickness (IMT) is a well-described marker of cardiovascular disease. In this study we aim to determine whether low-density lipoprotein (LDL) levels and disease-related mutation status can predict IMT in patients with severe familial hypercholesterolemia (FH) referred for or on LDL apheresis.Genetic screening, lipid profile testing, and IMT measurements were performed on a series of 33 severe FH patients (19 homozygous) on LDL apheresis treatments (LDL 447 ± 151 mg/dL, age range 6-60 years). Data were then compared with literature IMT-LDL data for normal subjects, mild FH patients, and severe FH patients (18, 41, and 6 studies, respectively).Age-adjusted IMT was linearly related to LDL levels over a wide range of values (500 mg/dL), except for the severe FH no-apheresis cohort. Alternatively, our severe FH population (mostly on apheresis) did follow the mild FH/control age-adjusted IMT-LDL relation.In severe FH, measuring LDL levels is more predictive of increased IMT than genetic screening.

Purpose. To study the distribution of breast mammogram density in Lebanese women and correlate it with breast cancer (BC) incidence.Methods. Data from 1,049 women who had screening or diagnostic mammography were retrospectively reviewed. Age, menopausal status, contraceptives or hormonal replacement therapy (HRT), parity, breastfeeding, history of BC, breast mammogram density, and final BI-RADS assessment were collected. Breast density was analyzed in each age category and compared according to factors that could influence breast density and BC incidence.Results. 120 (11.4%) patients had BC personal history with radiation and/or chemotherapy; 66 patients were postmenopausal under HRT. Mean age was52.58±11.90years. 76.4% of the patients (30–39 years) had dense breasts. Parity, age, and menopausal status were correlated to breast density whereas breastfeeding and personal/family history of BC and HRT were not. In multivariate analysis, it was shown that the risk of breast cancer significantly increases 3.3% with age (P=0.005), 2.5 times in case of menopause (P=0.004), and 1.4 times when breast density increases (P=0.014).Conclusion. Breast density distribution in Lebanon is similar to the western society. Similarly to other studies, it was shown that high breast density was statistically related to breast cancer, especially in older and menopausal women.

"Transfusion-related acute lung injury" (TRALI) is a post-transfusion lesional pulmonary edema, potentially severe, better defined since the conference of Toronto in 2004. The incidence of TRALI reported in France remains low in part because of its ignorance by physicians. The objective of our study was to evaluate retrospectively transfusion accidents with respiratory complications that occurred in Nancy University Hospital and reported to the haemovigilance between 1996 and 2006, from the software "Traceline" listing all the blood transfusion complications from signs observed. The analysis of the files has been performed by applying rigorously diagnostic criteria of Toronto. Forty-one cases of respiratory complications were found in 34,573 blood products. Ten cases of TRALI were diagnosed while only one case had been reported to the haemovigilance. The remaining nine cases were previously labeled transfusion-associated circulatory overload (TACO). No cases of TRALI have been identified in the ICU. Our work can find an incidence of TRALI 10 times greater than previously reported. Ignorance of TRALI and the lack of consensus definition before 2004 are not sufficient to explain these results. This study demonstrates the potential interest of database and computerized declaration system based on the symptoms observed. It highlights the vulnerability of the current haemovigilance too dependent on a single medical observer. Although TRALI are recognized as serious complications, sometimes requiring resuscitative care, our work was not isolated severe TRALI in ICU. Physician awareness of TRALI to the identification and to the declaration, including ICU should be continued. Finally, the diagnostic criteria for TRALI must be adapted to the ICU.

The authors report on 8 observations of respiratory complications, following catheterization of the superior caval system. They mention its clinical features, the seriousness of its development and the diagnostic procedure. The symptomatic treatment is based on the evacuation of the extravasation and the withdrawal of the catheter. Sometimes there has to be recourse to surgery. Finally, the authors emphasize the need for prevention of such typically iatrogenous complications.

Familial hypercholesterolemia (FH) is a genetic disorder with well-known genetic transmission and clinical course. Despite great recent progress, FH is still underestimated, under-diagnosed and thus undertreated. Furthermore it represents a significant healthcare challenge as a common risk factor for the premature development of coronary heart disease. The ScreenPro FH Project is an international network project aiming at improving complex care - from timely screening, through diagnosis to up-to-date treatment of familial hypercholesterolemia in Central, Eastern and Southern Europe. An important task for the project is to harmonise and unify diagnostic and therapeutic approaches in participating countries, where the situation differs from country to country. Countries with more experience should serve as a model for countries developing the FH network.Key words: diagnosis - familial hypercholesterolemia - screening - treatment optimization.