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AbstractBackground Most studies on long-term follow-up of patients with COVID-19 focused on hospitalised patients. No prospective study with structured follow-up has been performed in non-hospitalised patients with COVID-19.Objectives To assess long-COVID and post-COVID (WHO definition: symptomatic at least 12 weeks), describe lingering symptoms, their impact on daily activities, and general practice visits and explore risk factors for symptom duration in outpatients.Methods A prospective study of adult outpatients with confirmed SARS-CoV-2 infection and symptoms consistent with COVID-19 in 11 European countries, recruited during 2020 and 2021 from primary care and the community. Structured follow-up by phone interviews (symptom rating, symptom impact on daily activities and general practice visits) was performed at weeks 2, 4, 8, and 12 by study personnel. Data was analysed descriptively by using correlation matrixes and Cox regression.Results Of 270 enrolled patients, 52% developed long-COVID and 32% post-COVID-syndrome. When only considering the presence of moderate or (very) severe symptoms at weeks 8 and 12, these percentages were 28% and 18%, respectively. Fatigue was the most often reported symptom during follow-up. The impact of lingering symptoms was most evident in sports and household activities. About half (53%) had at least one general practice contact during follow-up. Obese patients took twice as long to return to usual health (HR: 0.5, 95%CI: 0.3–0.8); no other risk profile could predict lingering symptoms.Conclusion Long-COVID and post-COVID are also common in outpatients. In 32%, it takes more than 12 weeks to return to usual health.

Background: Between-country differences have been described in antibiotic prescribing for respiratory tract infection (RTI) in primary care, but not yet for diagnostic testing procedures and prescribing confidence. Aim: To describe between-country differences in RTI management, particularly diagnostic testing and antibiotic prescribing, and investigate which factors relate to antibiotic prescribing and GPs’ prescribing confidence. Design & setting: Prospective audit in 18 European countries. Method: An audit of GP-registered patient, clinical, and management characteristics for patients presenting with sore throat and/or lower RTI (n = 4982), and GPs' confidence in their antibiotic prescribing decision. Factors related to antibiotic prescribing and confidence were analysed using multi-level logistic regression. Results: Antibiotic prescribing proportions varied considerably: 40% in six countries. There was also considerable variation in point-of-care (POC) testing (0% in Croatia, Moldova, and Romania, and >65% in Denmark and Norway, mainly for C-reactive protein [CRP] and group A streptococcal [strep A] infection), and in laboratory or hospital-based testing (30% in Croatia, Georgia, Greece, and Moldova, mainly chest X-ray and white blood cell counting). Antibiotic prescribing was related to illness severity, comorbidity, age, fever, and country, but not to having performed a POC test. In nearly 90% of consultations, GPs were confident in their antibiotic prescribing decision. Conclusion: Despite high confidence in decisions about antibiotic prescribing, there is considerable variation in the primary care of RTI in European countries, with GPs prescribing antibiotics overall more often than is considered appropriate. POC testing may enhance the quality of antibiotic prescribing decisions if it can safely reverse decisions confidently made on clinical grounds alone to prescribe antibiotics.

Up to 80% of antibiotics are prescribed in the community. An assessment of prescribing by indication will help to identify areas where improvement can be made. A point prevalence audit study (PPAS) of consecutive respiratory tract infection (RTI) consultations in general practices in 13 European countries was conducted in January–February 2020 (PPAS-1) and again in 2022 (PPAS-4). The European Surveillance of Antibiotic Consumption quality indicators (ESAC-QI) were calculated to identify where improvements can be made. A total of 3618 consultations were recorded for PPAS-1 and 2655 in PPAS-4. Bacterial aetiology was suspected in 26% (PPAS-1) and 12% (PPAS-4), and an antibiotic was prescribed in 30% (PPAS-1) and 16% (PPAS-4) of consultations. The percentage of adult patients with bronchitis who receive an antibiotic should, according to the ESAC-QI, not exceed 30%, which was not met by participating practices in any country except Denmark and Spain. For patients (≥1) with acute upper RTI, less than 20% should be prescribed an antibiotic, which was achieved by general practices in most countries, except Ireland (both PPAS), Croatia (PPAS-1), and Greece (PPAS-4) where prescribing for acute or chronic sinusitis (0–20%) was also exceeded. For pneumonia in adults, prescribing is acceptable for 90–100%, and this is lower in most countries. Prescribing for tonsillitis (≥1) exceeded the ESAC-QI (0–20%) in all countries and was 69% (PPAS-1) and 75% (PPAS-4). In conclusion, ESAC-QI applied to PPAS outcomes allows us to evaluate appropriate antibiotic prescribing by indication and benchmark general practices and countries.

Objective To describe primary health care (consultation characteristics and management) for patients contacting their general practitioner (GP) with a respiratory tract infection (RTI) early on in the COVID-19 pandemic in contrasting European countries, with comparison to prepandemic findings.Setting Primary care in 16 countries (79 practices), when no routine SARS-CoV-2 testing was generally available.Design and participants Before (n=4376) and early in the pandemic (n=3301), patients with RTI symptoms were registered in this prospective audit study.Outcome measures Consultation characteristics (type of contact and use of PPE) and management characteristics (clinical assessments, diagnostic testing, prescribing, advice and referral) were registered. Differences in these characteristics between countries and between pandemic and prepandemic care are described.Results Care for patients with RTIs rapidly switched to telephone/video consultations (10% in Armenia, 91% in Denmark), and when consultations were face-to-face, GPs used PPE during 97% (95% CI 96% to 98%) of contacts. Laboratory testing for SARS-CoV-2 in primary care patients with RTIs was rapidly implemented in Denmark (59%) and Germany (31%), while overall testing for C reactive protein decreased. The proportion of patients prescribed antibiotics varied considerably between countries (3% in Belgium, 48% in UK) and was lower during the pandemic compared with the months before, except for Greece, Poland and UK. GPs provided frequent and varied COVID-related advice and more frequently scheduled a follow-up contact (50%, 95% CI 48% to 52%). GPs reported a slightly higher degree of confidence in the likely effectiveness of their management in face-to-face (73% (very) confident, 95% CI 71% to 76%) than in virtual consultations (69%, 95% CI 67% to 71%).Conclusions Despite between-country variation in consultation characteristics, access to SARS-CoV-2 laboratory testing and medication prescribing, GPs reported a high degree of confidence in managing their patients with RTIs in the emerging pandemic. Insight in the highly variable pandemic responses, as measured in this multicountry audit, can aid in fine-tuning national action and in coordinating a pan-European response during future pandemic threats.

Malignant melanoma has shown an increasing incidence during the last two decades, exhibiting a large spectrum of locations and clinicopathological characteristics. Although current histopathological, biochemical, immunohistochemical, and molecular methods provide a deep insight into its biological behaviour and outcome, melanoma is still an unpredictable disease, with poor outcome. This review of the literature is aimed at updating the knowledge regarding melanoma’s clinicopathological and molecular hallmarks, including its heterogeneity and plasticity, involving cancer stem cells population. A special focus is given on the interplay between different cellular components and their secretion products in melanoma, considering its contribution to tumour progression, invasion, metastasis, recurrences, and resistance to classical therapy. Furthermore, the influences of the specific tumour microenvironment or “inflammasome”, its association with adipose tissue products, including the release of “extracellular vesicles”, and distinct microbiota are currently studied, considering their influences on diagnosis and prognosis. An insight into melanoma’s particular features may reveal new molecular pathways which may be exploited in order to develop innovative therapeutic approaches or tailored therapy.

Background. The impact of SARS-CoV-2 infection alongside with influenza and RSV, the major viral agents in pediatric disordes, may be an important concern to the healthcare system. Clini-cal outcomes of the interaction are unknown. The aim of this systematic review is to contribute at establishing the prevalence of the co-infection, its clinical outcomes and potential risk factors. Methods. A systematical literature search was performed for papers published in PubMed, Sco-pus, Web of Science, Pedro and Cochrane Library, from January 2020 - the beginning of the COVID 19 pandemic - to June 2023. Our review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methods. Studies were eligible for inclusion if they approached the co-infection COVID 19 and influenza or RSV, and were available in English. Due to the fact that studies conducted on pediatric population are scarce, we included patients of all ages. Results. Out of 159 articles found, 12 were eligible for inclusion. The prevalence of co-infection was between 5% and 12 % for influenza viruses and 10% for RSV. The most common symptoms were high-grade fever, cough, headache, and shortness of breath and the most frequent complications were pneumonia and respir-atory distress. In terms of laboratory findings, co-infected patients presented with signifi-cant lymphopenia and pro-nounced inflammatory response, as well as a progressive ten-dency towards pneumonia and respiratory distress. Regarding the clinical outcomes of co-infection, the majority of articles in-dicated that simultaneous infection with SARS-CoV-2 and influenza predisposes to a more se-vere course of the disease(s), with a longer length of hospital stay and an increased risk of death.Conclusion. Our study underlines that the frequency of such co-infections, although not very high, predisposes to more frequent hos-pitalisations and a longer length of stay, complica-tions including admission to intensive care and more severe outcomes, including life-threatening events. It is therefore essential to determine the epidemiological impact of such an interaction nowadays, in order to in-form and adjust treatment and control and prevention strategies, for limiting co-infection between major respiratory viruses. Due to the lack of studies on children, we were unable to identify specific features of co-infections in this population. Therefore, more studies are needed to evaluate the paediatric population and consequently, our doctoral research en-deavour is warranted.

Background: Childhood obesity is one of the major challenges of public health policies. The problem of fatty liver in childhood, known as MAFLD (metabolic dysfunction-associated fatty liver disease), is of particular interest as the gold standard diagnosis technique is invasive (liver biopsy). Hence, efforts are made to discover more specific biomarkers for the MAFLD signature. Therefore, the aim of the study was to evaluate Osteonectin and Hsp27 as biomarkers for MAFLD diagnosis and to assess their links with auxological and biochemical profiles of overweight and obese pediatric subjects. Methods: A cross-sectional study in which we (re)analyzed data from the MR PONy cohort comprising 71 pediatric subjects. Auxological data, liver ultrasonography and biochemical serum profile were recorded. Lipid-derived indices and body composition indices were calculated. Nevertheless, serum Osteonectin and Hsp27 levels were assessed using an ELISA approach. Results: MAFLD prevalence was 40.8%. Higher Osteonectin levels were noted in MAFLD subjects versus non-MAFLD subjects and in dyslipidemic children regardless of their liver function status. Lipid-derived indices had good diagnostic capacity for MAFLD. Conclusions: We confirm Osteonectin as a MAFLD diagnosis biomarker in children. Also, lipid-derived indices are useful as metabolic-associated organ impairment markers in children even before the onset of obesity.

One of the most frequent benign tumor pathology in children is represented by infantile hemangiomas (IHs). Although they are mostly cutaneous, sometimes they can develop at visceral level, the liver being the most common localization. Objectives. Estimating visceral hemangiomas (VHs) prevalence, and identification of risk factors for VHs in patients with infantile cutaneous hemangiomas (ICHs). Materials and methods. 6 years cross-sectional study (2012-2017) including children diagnosed with ICHs, admitted in I.N.S.M.C “Alfred-Rusescu“. All patients underwent an ultrasound screening for the detection of VHs. In order to identify possible risk factors, we collected demographic and perinatal data. Outcomes. 138 patients diagnosed with infantile cutaneous hemangiomas (ICHs) were included, with a slight predominance of girls (58%). The prevalence of the VHs in our study was 7,24% (10 patients). The liver was the most common visceral localization (7 patients). Conclusions. Female gender, preterm birth, low birth weight, and multiple gestations were described as potential risk factors for IHs. In our study, only multiple gestations tend to be associated with visceral hemangiomas, but without a significant statistical correlation.

Objectives. The aim of this study was to present and describe specific macroscopic and microscopic placental findings in patients with hypoxic-ischemic encephalopathy (HIE). Materials and methods. We conducted an observational prospective study which included 84 patients diagnosed with HIE and had available placental histopathological examination. HIE diagnosis was performed according to Sarnat Score. Both macroscopical and microscopical placental lesions were identified. Patients were divided into 2 groups according to the presence of placental lesions. Outcomes. Placental lesions were associated with HIE. Patients with both HIE and placental lesions had lower pH value (p

One of the affected organs in cystic fibrosis (CF) is the pancreas, mainly translated into exocrine pancreatic insufficiency. Although rare, acute pancreatitis (AP) has been described, mostly in pancreatic sufficient patients. Objectives. Estimating AP prevalence in CF pediatric population of the I.N.S.M.C. „Alessandrescu Rusescu” CF centre. Material and methods. 5 year retrospective study (2011-2016) including INSMC CF centre pediatric population aged 3-18 years. PA diagnosis was established on the presence of minimum 2 criteria between: characteristic abdominal pain, x3 normal value for age elevation of amylase/lipase, medical imaging evaluation suggestive for AP. Patients were evaluated with different criteria including PIP score of predicting AP risk. Outcomes. 48 patients were included with a slight female predominance (54%). 3 of them presented diagnostic criteria for AP (6,25%), all heaving pancreatic insufficiency and high PIP score (low risk of developing AP); 2 of them have low compliance with pancreatic enzymes substitution therapy; one of them presented recurrent episodes of AP. Conclusions. AP is a rare CF complication. It can be easily missed due to a large number of abdominal pain and emesis causes in CF patients. Although it is usually associated with pancreatic sufficiency, all our patients were pancreatic insufficient.

Malnutrition continues to be a major issue concerning pediatric cystic fibrosis patients’ medical care. Supplementary diagnostic association with food allergy in a cystic fibrosis patient leads to worse nutritional status decline. This particular association determines low quality of life and life expectance impairment. Low caloric intake, recurrent pulmonary infections, maldigestion and malabsorption, low treatment adherence, genetic susceptibility and chronic infections are all risk factors and/or causes of malnutrition in cystic fibrosis patients. The aim of our study was to evaluate the prevalence of IgE mediated food allergies in cystic fibrosis patients. A secondary objective was to assess nutritional status in cystic fibrosis patients with food allergies after exclusion diet. In order to accomplish our objectives, we conducted a descriptive, retrospective study on a 68 pediatric patient cohort with cystic fibrosis (CF). All children were diagnosed and followed in the Regional center for CF of INSMC “Alessandrescu-Rusescu”, Bucharest, between 2011 and 2016. After data collection and statistic analysis we observed a prevalence of 11.7% of food allergies in our cystic fibrosis patients cohort. Also, specific exclusion diet impact on nutritional status was evaluated.

With an incidence reaching almost 10%, infantile hemangiomas represent the most common tumors of infancy. Although the majority of hemangiomas develop on the skin, parenchymal tumor may occur in all organs. Parotid gland hemangiomas represent the most frequent vascular tumor of all salivary glands neoplasms. Ultrasound is a very helpfull tool in establishing the diagnosis of parotid gland infantile hemangioma as well as in the follow up of evolution durring treatment.

Infantile hemangiomas are the most frequent tumors of infancy, with an incidence reaching almost 10% (1). In children with more than 5 skin hemangiomas it has been noticed a highly association with visceral hemangiomas, the liver being the main site for their localization (2). Regarding therapeutic approach, if for skin hemangiomas the treatment is well established, for hepatic infantile hemangiomas clear guidelines are still necessary.

Struma ovarii is a rare type of ovarian teratoma primarily composed of over 50% thyroid tissue. Its occurrence is reported in 2–5% of all ovarian teratomas, with approximately 0.5% to 10% showing malignant transformation. Managing it during pregnancy poses significant challenges as pregnancy can promote the growth of malignant struma ovarii due to elevated levels of ovarian and pregnancy-related hormones, including estrogen, progesterone, and human chorionic gonadotrophin (hCG). Most ovarian tumors, including struma ovarii, are detected during routine ultrasonography in the first and second trimesters, often as acute emergencies. Diagnosis during pregnancy is rare, with some cases incidentally discovered during cesarean section when inspecting the adnexa for ovarian cysts. This review explores the diagnostic, management, and therapeutic approaches to struma ovarii during pregnancy.

Atypical polypoid adenomyoma (APAM) is a rare polypoid benign tumor of the uterus that causes irregular vaginal bleeding in women of reproductive age. It has the potential for malignant transformation, but it does not metastasize. APAM may coexist with endometrial hyperplasia and adenocarcinoma, usually leading to misdiagnosis. Histopathologically, it is a biphasic tumor, represented by the endometrioid glands with a complex histoarchitecture, with sometimes squamous morular metaplasia or cytologic atypia, interspersed with a fibromyomatous stroma. This tumor has a high incidence of recurrence. We present a very rare case of a 21-year-old patient, a virgin, without a significant medical history, with a bleeding mass occupying the vagina. The mass was excised using forceps, scissors, and a suture of the visible pedicle. After a four-year follow-up and no additional medical treatment, no relapse was observed. Given the risk of recurrence and progression, APAM might be treated via a hysterectomy in patients with no desire for pregnancy. Due to a lower recurrence rate, the conservative treatment of atypical polypoid adenomyoma performed via an operative hysteroscopy represents the best choice. Previously diagnosed in hysterectomy specimens, with the introduction of better-performing indirect imaging techniques, adenomyosis is a clinical entity that has the possibility of being diagnosed in the presurgical stage.

The perivascular adipose tissue (PVAT) has been recently recognized as an important factor in vascular biology, with implications in the pathogenesis of cardiovascular diseases. The cell types and the precursor cells of PVAT appear to be different according to their location, with the component cell type including white, brown, and beige adipocytes. PVAT releases a panel of adipokines and cytokines that maintain vascular homeostasis, but it also has the ability of intervention in the pathogenesis of the atherosclerotic plaques development and in the vascular tone modulation. In this review, we summarize the current knowledge and discuss the role of PVAT as a major contributing factor in the pathogenesis of ischemic coronary disease, hypertension, obesity, and diabetes mellitus. The new perspective of PVAT as an endocrine organ, along with the recent knowledge of the mechanisms involved in dysfunctional PVAT intervention in local vascular homeostasis perturbations, nowadays represent a new area of research in cardiovascular pathology, aiming to discover new therapeutic methods.

Placenta accreta spectrum disorder (PAS) has an increased frequency due to the high number of cesarean sections. The abnormal placentation associated with a retained placenta can cause persistent uterine bleeding, with ultrasound Doppler examination being the main choice to assess the uterine hemorrhage. An acquired uterine arteriovenous malformation (AVM) may occur because of uterine trauma, spontaneous abortion, dilation and curettage, endometrial carcinoma or gestational trophoblastic disease. The treatment for abnormal placentation associated with AVM can be conservative, represented by methotrexate therapy, arterial embolization, uterine curettage, hysteroscopic loop resection or radical, which takes into consideration total hysterectomy. Therapeutic management always considers the degree of placental invasion, the patient hemodynamic state and fertility preservation. Considering the aspects described, we present a case of retained placenta percreta associated with acquired uterine AVM, with imagistic and clinical features suggestive of a gestational trophoblastic disease, successfully treated by hysterectomy, along with a small review of the literature, as only a few publications have reported a similar association of diagnostics and therapy.

BMI-1 is a key component of stem cells, which are essential for normal organ development and cell phenotype maintenance. BMI-1 expression is deregulated in cancer, resulting in the alteration of chromatin and gene transcription repression. The cellular signaling pathway that governs BMI-1 action in the ovarian carcinogenesis sequences is incompletely deciphered. In this study, we set out to analyze the immunohistochemical (IHC) BMI-1 expression in two different groups: endometriosis-related ovarian carcinoma (EOC) and non-endometriotic ovarian carcinoma (NEOC), aiming to identify the differences in its tissue profile. Methods: BMI-1 IHC expression has been individually quantified in epithelial and in stromal components by using adapted scores systems. Statistical analysis was performed to analyze the relationship between BMI-1 epithelial and stromal profile in each group and between groups and its correlation with classical clinicopathological characteristics. Results: BMI-1 expression in epithelial tumor cells was mostly low or negative in the EOC group, and predominantly positive in the NEOC group. Moreover, the stromal BMI-1 expression was variable in the EOC group, whereas in the NEOC group, stromal BMI-1 expression was mainly strong. We noted statistically significant differences between the epithelial and stromal BMI-1 profiles in each group and between the two ovarian carcinoma (OC) groups. Conclusions: Our study provides solid evidence for a different BMI-1 expression in EOC and NEOC, corresponding to the differences in their etiopathogeny. The reported differences in the BMI-1 expression of EOC and NEOC need to be further validated in a larger and homogenous cohort of study.

Aim: To identify problems in the utilization of the logbook in the Centers where it is already implemented and to identify ways to extend the process in the Centers where the implementation process didn't start. Methods: A focus group with tutors and medical residents is to be organized. The research questions are: Is the logbook a useful orientation tool for the resident? Is the format of the log book friendly enough for data registration? Is there a need for improvement? How will function the dedicated log book for family medicine in the light of the unified logbook that is proposed by the Ministry of Health? Is the portfolio of clinal maneuvers a useful tool? How will the evaluation process at the end of the residency program will be done? Results: We expect that information will show an underutilization of the logbook and some barriers of understanding from the part of the medical resident's in the functions of the logbook. We expect to agree on the general principles of the evaluation at the end of the residency training. We shall be able to draw a position paper concerning the functions of the logbook and its role in the evaluation process. Conclusions: It is of major importance that all medical Universities unite in the effort of improving the quality of training in the residency program of Family Medicine. [ABSTRACT FROM AUTHOR]