Background: Epicranial cortical stimulation (ECS) is a minimally invasive neuromodulation technique that works by passing electric current between subcutaneous electrodes positioned on the skull. ECS causes a stronger and more focused electric field in the cortex compared to transcranial electric stimulation (TES) where the electrodes are placed on the scalp. However, it is unknown if ECS can target deeper regions where the electric fields become relatively weak and broad. Recently, interferential stimulation (IF) using scalp electrodes has been proposed as a novel technique to target subcortical regions. During IF, two high, but slightly different, frequencies are applied which sum to generate a low frequency field  at a target subcortical region. We hypothesized that IF using ECS electrodes would cause stronger and more focused subcortical stimulation than that using TES electrodes.Objective: Use computational modeling to determine if interferential stimulation-epicranial cortical stimulation (IF-ECS) can target subcortical regions. Then, compare the focality and field strength of IF-ECS to that of interferential Stimulation-transcranial electric stimulation (IF-TES) in the same subcortical region.Methods: A human head computational model was developed with 19 TES and 19 ECS disk electrodes positioned on a 10–20 system. After tetrahedral mesh generation the model was imported to COMSOL where the electric field distribution was calculated for each electrode separately. Then in MATLAB, subcortical targets were defined and the optimal configurations were calculated for both the TES and ECS electrodes.Results: Interferential stimulation using ECS electrodes can deliver stronger and more focused electric fields to subcortical regions than IF using TES electrodes.Conclusion: Interferential stimulation combined with ECS is a promising approach for delivering subcortical stimulation without the need for a craniotomy. The use of electrical brain stimulation to modulate neural activity is a rapidly growing field with many novel methods currently being proposed and evaluated . One of Recently a groundbreaking study introduced a novel electrical brain stimulation technique that can target deep brain regions non-invasively using interfering fields . This teIn a recent computational study on IF, In this study, we hypothesized that IF using ECS electrodes would produce a stronger and more focused subcortical stimulation than IF using TES electrodes. To test this hypothesis, we used a human head computational model with either a set of 19 ECS electrodes or 19 TES electrodes. Then, we pre-defined a number of subcortical targets and calculated the optimized electrode configurations for each of the two approaches. Finally, we compared the fields’ strength and focality obtained with IF-ECS and IF-TES at the target points and showed that IF-ECS can target subcortical regions with more focused and stronger fields than is achievable with IF-TES.A high-precision human head computational model was generated using the multimodal imaging–based detailed anatomical (MIDA) model  and thenAfter tetrahedral meshes were generated using ScanIP, the volumetric model was imported to COMSOL multiphysics 5.3  to calculate the electric field distribution for each electrode separately. Thus, a total of 38 electric field simulations were required. Each simulation estimated the electric field distribution through one of the ECS or TES electrodes with a 1 mA (zero to peak amplitude) current being set as a boundary condition for the finite element problem. Electric current was applied between the selected electrode and a reference electrode defined as the bottom of the head representing a far body reference electrode . FinallySkin = 0.465 S/m, σSkull = 0.01 S/m, σCSF = 1.65 S/m, σGM = 0.27 S/m, σWM = 0.126 S/m, σPDMS = 10–19 S/m, σpt = 9.43 × 106 S/m  for the tissues were always: σ 106 S/m . The resN × m where m represents the number of electrodes and N the number of brain elements (n) multiplied by 3 (N = n × 3) taking into account the electric field at the different coordinate axes . Given the matrix A we can now estimate the total absolute electric field (E) generated in the brain by the electrode arrays as following:Above, the electric field vector was calculated for each electrode separately assuming that the current is only passed between the selected electrode and the reference. Here, the resultant electric field for simultaneous multiple electrodes stimulation is calculated. Using Matlab, the electric field distributions for ECS and TES electrodes were sorted in separate matrices Amax. Therefore, by adjusting the values in vector s, the induced electric field in the brain can be steered. This is essential when aiming to stimulate with a maximum field a given brain area while avoiding others. To maximize the electric field at a target brain element, a similar approach to where s is a vector of length m representing the applied electric current to each electrode. Eq. 4 ensures all currents entering the brain must exit and Eq. 5 ensures that the maximum applied electric current is below a maximum value Iwhere e is the desired brain electric field vector having length N and specifying which brain element to target and what the desired field direction  is. Each element in the vector e has a value between zero and one with higher values indicating the target area. In this study, the target point was set to have a value of one and then to decrease in a Gaussian distance relation when moving away from that target. To minimize the electric field at non-target brain elements the following constraint on the non-target electric field power was applied to the optimization approach (6):max is an input parameter that specifies the maximum allowed electric field power in the non-target brain elements. A low Pmax value restricts the electric field in the non-target region but might also limit the applied electric current leading to lower fields in the target. The default value of Pmax was calculated as Pmax0 = eT A(AT Γ2A)–1 ATe (such that (| | .| |) is the L2-norm and Γ is a diagonal matrix with size N and having diagonal component with values between zero and one to specify the weight of each element in the penalty form. In contrast to e, Γ has a value of zero at the target and increases in a Gaussian distance relation when moving away from that target. PA)–1 ATe .1| |,| | E2| |) where E1 and E2 are the electric fields generated by the sources s1 and s2 at the given brain element, respectively. To maximize the resultant interferential field at the target, s1 and s2 were calculated by solving the following optimization problem:So far it was assumed that the electric current applied to all electrodes was sinusoidal and from the same source, meaning that they have the same frequency and phase. However, when two groups of electrodes receive electric current from two different sinusoidal sources with slightly different high frequencies, interferential phenomenon occurs. This section aims to calculate the optimal electrode configuration, of both IF-ECS and IF-TES, to target any pre-selected point in the brain with the resultant interferential low frequency field. Thus, we sought to use an approach similar to To minimize the resultant interferential field at the non-target elements the following constraint to the above optimization was applied:max values as described by To determine if IF-ECS can target subcortical regions and compare the focality and field strength of IF-ECS to that of IF-TES, a number of subcortical targets were preselected. The selected regions are the left subthalamic nucleus (STN), right ventral intermediate nucleus (VIM), left hypothalamus and the left insula, which are of clinical and research interest for neuromodulation. Each region was defined by one point. Then the optimal electrode configurations were calculated for both IF-ECS and IF-TES for a series of PBecause IF-ECS works using minimally invasive electrodes, limiting the number of implanted electrodes becomes important. However, this comes at the cost of electric field strength and focality. To test the effect of limiting the electrodes number on such parameters, the values were recalculated with only the electrodes with the highest applied current accounting for at least 75% of the total applied current. Then the applied currents were proportionally readjusted to ensure a total of 1 mA current was injected. The selection was done for each of the two sources (s1 and s2) and for the cathode and anode poles separately.x-axis). To adjust the balance between maximizing the interferential field at the target and minimizing the field at the non-target regions, the solution for Eqs. 9–12 was solved for several values of Pmax varying between Pmax0 × 10–3 and Pmax0 × 105 in a step of 101.For each of the pre-selected targets the optimal electrode configuration was calculated given a predefined desired electric field direction . This solution was selected as the grand optimal configuration and was used for further analysis.The optimization method aims to maximize the interferential fields at the target and minimize it elsewhere. To adjust the leverage between the two factors, PEpicranial cortical stimulation delivers stronger and more focused non-interferential electric field than TES . To testmax values, higher electric fields were reached in the target regions, but this comes at the cost of focality. This is in line with the findings using transcranial electrodes (The first aim of this study was to use computational modeling to optimize the electrodes configuration and test the ability of IF-ECS to target subcortical regions. The optimization method we applied was already investigated in the context of TES and it was shown to successively work . In thisectrodes .The second aim was to compare the outcomes of IF-ECS and IF-TES. It has already been shown that ECS induces a stronger and more focused cortical electric fields than TES. However, this is the first study to compare the interferential fields induced by both techniques. The results show that IF-ECS induces higher and more focused interferential fields than IF-TES. On average this was an increase of 3.8 times in field amplitude and an improve of 9% in focality. Moreover, ECS has the advantage that higher stimulation amplitude are achievable, due to the insulating back layer that blocks the current from passing through the skin . TherefoA limitation of this study is that it focuses on the induced interferential fields in the brain but not the non-inferential ones. However, this is based on our assumption that neurons will respond to low frequency electric fields but not to that with high frequencies. While there is evidence to support our assumption , testingVarious studies have focused on the effects of anatomical differences and electrode dimensions on the electric field distribution during transcranial and epicranial stimulation . A recenEpicranial cortical stimulation is a novel technique that was shown to induce strong and focused electric field in the cortex . This stThe raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.AK and ML: conceptualization, methodology, writing, and review. BA: methodology, writing, and review. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Right thoracotomy with ligation of the fistula with end to end anastomosis was performed successfully without complications. Breastfeeding initiated and the child discharged after she started gaining weight. Early post-operation complication (anastomotic stricture) was noticed after 2 weeks; however, corrected with endoscopic balloon dilatation. Currently, the child is healthy weighing 10kgs at 18 months age.Tracheoesophageal fistula is a challenging anomaly with a rare prevalence with symptoms mainly respiratory, sometimes digestive. We present a rare case of oesophageal atresia with distal Tracheoesophageal fistula in a female child whose mother presented with severe oligohydramnios on ultrasonography with intrauterine growth retardation before caesarean section. After the birth of preterm and very low birth weight neonate, we initially diagnosed as respiratory distress syndrome with club foot. However, we diagnosed oesophageal atresia with distal Tracheoesophageal fistula on 2 Further, she was referred to our centre . Repeat USG was done at 31 weeks which revealed severe oligohydramnios with amniotic fluid index (AFI) 1.5cm and intrauterine growth retardation (IUGR) with the expected fetal weight of 1365 grams only. Emergency lower segment caesarean section was performed with prior administration of 2 doses of dexamethasone (12mg) and prophylactic antibiotics to the mother. A female baby was born with a birth weight of 1.2 kilograms and was immediately transferred to the neonatal intensive care unit (NICU) due to respiratory distress. There was no gross congenital anomaly (no murmur) noted except the club foot. She was managed conservatively with intravenous fluids, antibiotics and non-invasive ventilation (Continuous positive airway pressure (CPAP) at 6 centimetre water) with an initial diagnosis of respiratory distress syndrome with a pre-term baby with very low birth weight. Further, NG tube insertion was tried but failed to pass beyond 10 cm for feeding purpose. Therefore, a red rubber catheter was inserted and a chest X-ray was performed which demonstrated EA with TEF. Eventually, surgical correction was planned with all the pre-operative evaluation done to rule out other associated anomalies and complications. Right thoracotomy with ligation of the fistula with end to end anastomosis was performed without any perioperative complications .Additionally, a prophylactic chest tube was kept in situ and the NG tube was fixed. Furthermore, post-operatively continuous monitoring of vitals, haemoglobin, electrolytes, nasogastric and chest tube care, antibiotics coverage (Piperacillin-tazobactam + Metronidazole), and maintaining neutral neck position were done. Repeat chest X-ray on the first post-operative day (POD) showed atelectasis of the left lung and chest tube in situ on right . NG feed4 A rare clinical condition but a challenging congenital anomaly which was first reported in 1697 by Thomas Gibson, has always made managing this condition to be very much strenuous.4 The abnormality is itself a huge challenge, as a rule, comes in association with one other abnormality .1 These abnormalities can be explained as in Table 1. The TEF classification is determined by the location of the oesophageal atresia and the presence of any associated fistula to the trachea.2 Five different variants have been clinically described, the first described by Vogt in 1929, and modified by Gross in 1953. Thus, two classifications are used today which includes: (i) EA with distal TEF , (ii) Isolated EA without TEF , (iii) TEF without atresia or H-type TEF , (iv) EA with proximal TEF , and (v) EA with proximal and distal TEF .4Tracheo-oesophageal fistula is an abnormal communication between the trachea and the oesophagus.1 The presentation may vary depending upon the presence or absence of EA. New-borns with EA present immediately after birth with excessive secretions that cause drooling, choking, respiratory distress, and feeding inability. Gastric distension is a common complication of a fistula between the trachea and the distal oesophagus. In EA subsequent inability to swallow typically cause polyhydramnios in utero, a common finding on antenatal USG scanning.2 However, in our case, the mother presented with oligohydramnios which led our doubts overshadowed towards correct diagnosis and hence, following the scan done at 31st weeks of gestation a diagnosis of oligohydramnios with intrauterine growth retardation was made. A very low birth weight infant with the birth weight of 1.2 kgs delivered via a caesarean section without gross anomaly except for club foot. Additionally, there was no excessive secretions. This contrasts with the typical presentation of esophageal atresia. One reason behind the cause of severe oligohydramnios in our case after reviewing the history again could be per vaginal leaking of amniotic fluid. Prenatal diagnosis with USG scans can be helpful when a scan in a mother with polyhydramnios shows the absence of a stomach or a small stomach.1 Routine USG scans done between 16-20 weeks of pregnancy can aid the diagnosis but the findings are not specific, are subjective and occasionally transient. This might be due to the reason that polyhydraminos is only diagnostic if TEF is associated with EA. MRI can be complementary to USG as it can be highly predictive although questions have been raised over the feasibility and cost.2 After birth, if EA is suspected, a radiopaque 8 French (in preterm infants) or 10 French (in term infants) NG or feeding tube should be passed. In patients with atresia, the NG tube coils at 10 to 12 cm.5 After passing the tube, chest radiographs  including the entire abdomen should be obtained to confirm the position of the tube.4 In patients with EA, the air in the stomach confirms the presence of a fistula. In our case, as she was delivered pre-term and had very low birth weight, she had a higher risk of developing respiratory distress and so was admitted in NICU  and started on intravenous fluids, antibiotics and non-invasive ventilation with a diagnosis of acute respiratory distress syndrome. This misled us to establish the correct diagnosis. However, when a NG tube was inserted in the NICU for the purpose of feeding, the tube could not be inserted; additionally, continuous frothy secretion was noticed only after that point. This gave a clue to us to suspect TEF and hence, a red rubber tube was inserted and a chest x-ray was performed.TEF presents in a new-born by copious salivation associated with choking, coughing, vomiting, and cyanosis during the onset of feeding.2 Earlier to this many attempts were made and many surgical procedures tried which failed and this proves how difficult the procedure can be.4 The survival rate of such cases which was once hopeless has improved and reached 100%.5 For successful management care and precision has to be given since the time of diagnosis and needs special pre-operative, intra-operative and post-operative care and management.5 An open surgery which includes thoracotomy with end to end anastomosis of the esophagus with correction of fistula has been reducing the mortality rate of the patients diagnosed with this challenging condition.2 Currently various endoscopic and other surgical techniques are being tried in various hospitals with some promising outcomes.6 In cases of neonates with very low birth weight and extremely low birth weight primary repair of EA and closure of a TEF seems to be a better option amongst the open surgical procedure and has proven to enhance the better outcome than the staged repair;7 however controversies exist here as well.8 In our case, we performed right thoracotomy with ligation of the fistula with end to end anastomosis without any peri-operative complications. Many surgeons prefer stage repair in VLBW neonate over primary repair; however, here we performed primary repair as patient was from remote region with low socio-economic condition leading to refusal for stage repair or follow ups.Following multiple innovative ways aimed at the correction, it was 1941 when a successful surgical correction was performed by Cameron Haight.4 The prognosis may be influenced by the presence of major anomalies such as cardiac malformation, renal deformity, external risk factorssepsis, respiratory failure; it is also influenced by the neonatal caregivers.9 Undoubtedly, any efforts to reduce the incidence of the external risk factors may decrease the mortality rate.Complications are mostly post-operative and include anastomotic leak (10-20%), anastomotic strictures (30-40%) as in our case which was managed with balloon dilatation, recurrent TEF (5-14%), tracheomalacia (10%), gastroesophageal reflux (40%), and respiratory infections.9 however, we were lucky enough and our patient proved herself a survivor. Spitz classification deals with classification and survival based on weight.2 This classification states that the survival rate of infants below 1.5 kgs of birth weight without any major cardiac anomaly to be between 59-82%.4 Despite our strengths, we were unable to diagnose this anomaly during pre-delivery (LSCS) USG scanning and the child, unfortunately, developed an early complication as oesophageal stricture; however, oesophageal stricture was successfully managed endoscopically with balloon dilatation.The early diagnosis of the case, within 2 days of delivery despite normal antenatal check-up, and the most successfully performed surgery, good post-operative NICU care without any intra or post-surgical complication, are the prime strength of our study. Very low birth weight and prematurity were some of the worth considering factors in the case of our patient as both of them have been taken as factors that adversely affect the outcome;Although TEF is uncommon in newborn babies, it is wise to USG screening during the antenatal check-up and if doubtful, MRI. Sometimes, they may present with an atypical presentation like in our case with oligohydramnios. Early diagnosis and good care to prevent external risk factors and ultimately surgical correction provide a good prognosis unless the absence of major organ anomalies.


The “developmental origins of health and disease” (DOHaD) hypothesis refers to the influence of early developmental exposures and fetal growth on the risk of chronic diseases in later periods. During fetal and early postnatal life, cell differentiation and tissue formation are influenced by several factors. The interaction between genes and environment in prenatal and early postnatal periods appears to be critical for the onset of multiple diseases in adulthood. Important factors influencing this interaction include genetic predisposition, regulation of gene expression, and changes in microbiota. Premature birth and intrauterine growth restriction (IUGR) are other important factors considered by the DOHaD hypothesis. Preterm birth is associated with impaired or arrested structural or functional development of key organs/systems, making preterm infants vulnerable to cardiovascular, respiratory, and chronic renal diseases during adulthood. Growth restriction, defined as impaired fetal growth compared to expected biological potential in utero, is an additional negative factor increasing the risk of subsequent diseases. Environmental factors implicated in the developmental programming of diseases include exposure to pollution, stress, drugs, toxic agents, nutrition, and exercise. The DOHaD may explain numerous conditions, including cardiovascular, metabolic, respiratory, neuropsychiatric, and renal diseases. Potential antenatal and postnatal preventive measures, interventions, and future directions are discussed. The concept that early life events predict adult health and disease was initially proposed in 1986, when Barker et al. showed that adults who had low birth weight (<2.5 kg) were at higher risk of cardiovascular disease [In this narrative review, we will propose examples of diseases and discuss potential preventive measures with potential long-term impacts.Critical perinatal factors influencing organogenesis and predisposition to disease include genetic factors, interaction between genes and environment, duration of gestation, and maternal–fetal interactions.The interaction between genes and the environment in prenatal and early postnatal periods appears to be critical for the onset of diseases in adulthood and has the potential to be modified by interventions. Important factors influencing this interaction include regulation of gene expression and changes in microbiota  and microbiome (their collective genomes) . Across Premature birth and intrauterine growth restriction ( IUGR) are other important factors considered by the the DOHaD hypothesis. Preterm birth is associated with impaired or arrested structural or functional development of key organs/systems, making preterm infants vulnerable to several diseases at adulthood .Another implication of preterm birth is the lack of hormonal supply with steroid hormones (estradiol and progesterone), which is typically observed among term infants. Both hormones increase up to 100-fold during pregnancy in the mother and the fetus. After preterm birth, these hormones drop dramatically in the mother and the newborn within hours. This is a physiological event at term, but the very preterm infant is disrupted from this huge hormonal supply at a much earlier developmental stage. Preliminary clinical data showed that the replacement of estradiol and progesterone in very preterm infants may improve lung development and neurological outcome ,6.Growth restriction, defined as impaired fetal growth compared to expected biological potential in utero, is an additional negative factor increasing the risk of subsequent diseases . Fetal gTrue IUGR, compared to constitutional smallness, is a pathological condition in which the placenta fails to deliver an adequate supply of oxygen and nutrients to the developing fetus . DiffereInfants with IUGR, compared appropriately grown gestational age infants, have a significantly higher risk of mortality and neonatal complications with long-term consequences ,11,12. TChanges in microbial population and their interactions with genes and the environment in different organs  have been linked to the development of several diseases, including metabolic syndrome, cardiovascular diseases, and respiratory and psychiatric disorders ,15.Suboptimal nutrition and extrauterine growth restriction also increase the risk of complications of prematurity . HoweverEnvironmental factors implicated in the developmental programming of diseases include exposure to pollution, stress, drugs, toxic agents, exercise, and nutrients ,21,22.hypertension [Preterm birth and IUGR can result in structural changes of the cardiovascular system, such as the development of short sarcomeres in cardiomyocytes and vascular remodeling (muscularization), resulting in increased arterial stiffness. IUGR and preterm birth are independent risk factors for the development of subsequent cardiovascular disease and rtension ,24,25. Trtension .According to a recent study, young adults born preterm have evidence of greater diffuse myocardial fibrosis in the left ventriculum that relates to the degree of prematurity, resulting in impaired diastolic function . GreaterInfants born afterIUGR have increased vascular stiffness and increased intima-media thickness, resulting in decreased vascular compliance and impaired endothelial-dependent vasodilation. These vascular alterations may increase myocardial workload and contribute to the development of hypertension in adulthood ,29,30.Bassareo et al. suggested that central aortic elasticity in former extremely preterm infants is impaired when compared with that of term-born controls, particularly in the context of intrauterine growth restriction . Animal The postnatal environment plays an important role in reducing or enhancing the likelihood of disease expression: proposed postnatal factors include nutrient availability and stress . In theiIn a meta-analysis by Horta et al., breastfeeding, regardless of IUGR status, decreased the likelihood of developing major cardiovascular risk factors, including type 2 diabetes and obesity; however, no association was observed with blood pressure . Lindberobesity, and the risk increases with decreasing gestational age [Prematurity is also a major risk factor also for onal age . Among oonal age . Abdominonal age .diabetes later in life. Preterm and early term birth were associated with up to 1.5-fold increased risk of type 1 and type 2 diabetes from childhood into early to mid-adulthood in a large population-based cohort [In addition to family history and unhealthy lifestyle factors, early life exposures have been identified as potential risk factors for the development of d cohort . These fd cohort . Pretermd cohort . Other cd cohort .Most studies show a 30–40% reduction in insulin sensitivity in children and young adults born very preterm (<32 weeks’ gestation) in comparison with those born at term . AnotherStroke is one of the most common causes of disability among adults worldwide. Previous studies have indicated that low birth weight is associated with an increased risk of adult stroke in men and that birth weight is inversely associated with the risk of stroke in women [in women ,55. The in women . Some stin women , making In humans 60% of the nephrons develop during the third trimester of gestation, mostly between 28 and 34 weeks of gestation. The final endowment of nephrons is both dependent on gestational age at birth and intrauterine environment. The principal factor, among others, which determines nephron number is birth weight . An evenChronic kidney disease (CKD) is defined as the reduction of reduced glomerular filtration rate (GFR) up to end-stage renal disease (ESRD), proteinuria, or both. Prevalence of ESRD is increasing worldwide. Reduced nephron endowment has been proposed as playing a determinant role in the pathogenesis of CKD [s of CKD . Reduceds of CKD . Concomis of CKD . Low birs of CKD . In pretWhile rapid postnatal growth and/or overfeeding enhances the “vulnerability state” acquired in utero and accelerates the development of adult diseases (“mismatch hypothesis”), slow postnatal growth and breastfeeding in particular (possibly through reduced protein and sodium intakes) tend to prevent such diseases . Nephronasthma, in up to 75% of infants born below 30 weeks of gestation [Conditions such as prematurity and its complications, fetal growth restriction, and inflammation have been associated with long-term pulmonary morbidity, including estation ,65. Premestation . Proposechronic obstructive pulmonary disease (COPD) has been observed in subsets of extremely preterm-born adults, as lung function will commence its normal age-related decline from subnormal levels, possibly at steeper trajectories [BPD and pulmonary hypertension [Early-life inflammatory insults, as in neonatal respiratory distress and bronchopulmonary dysplasia (BPD), may hamper the development of properly organized pulmonary interstitium, with consequences for acinar structure and function, peribronchial airway support, and elastic recoil pressures . Early oectories . It has ectories . Structurtension . BPD hasrtension . Patientrtension ,73. Howertension . In a strtension .Difficulties in this research area, characterized by a long time span between birth and the occurrence of complications, include the rapid evolution of obstetric and neonatal care  that can have an important influence on long-term outcomes.Increased risk of impaired neurodevelopment and psychological dysfunctions in the first four decades of life were reported in preterm infants, in small for gestational age (SGA) infants compared to appropriate for gestational age (AGA) infants and in pregnancies complicated by maternal diabetes ,76,77. Uantenatal measures are: improved identification of subjects with increased risk of complications , dietary modifications during pregnancy to ensure normalization of body weight, zinc and iron levels, glycemia and blood pressure control, lifestyle measures , reduced stress and exposure to pollution), and management of chronic diseases. Some of these measures are currently being evaluated in the context of clinical studies [Several preventive measures can be identified and considered to promote long-term health. Examples of useful  studies ,86,87,88The prevention of preterm birth and enhanced maturation  is of paramount importance. Global policies to enhance health, particularly in low-income countries have been advocated . SpecifiFinally, the administration of drugs during high-risk pregnancies  is another potential measure: sildenafil has been investigated but increased fetal death in a clinical trial has led to discontinuation of the study ; vasculaPostnatal interventions in the early phases of life include promotion of breastfeeding, optimization of nutrition and growth , adequate follow-up of patients at high risk, appropriate resource allocation [location . The chalocation , pre-proNovel drugs under investigation include lactoferrin and stem cell administration ,97.Knowledge translation, the process of putting knowledge into action, is of paramount importance to ensure the use of research findings in decision-making . In factIn conclusion, developmental programming is emerging as a new concept for the explanation of several diseases in children and adults. The characterization of underlying mechanisms and the identification of preventive measures and treatment are of great importance in order to promote health and prevent the development of several chronic diseases.


In Senegal, studies focusing specifically on vaccination coverage with the Bacille de Calmette et Guérin (BCG) vaccine, the birth dose of oral polio vaccine (OPV zero dose) and the birth dose of hepatitis B (HepB-BD) vaccine are insufficient. This study aimed to highlight vaccination coverages with birth doses and factors associated with timely vaccination in Podor health district.A cross-sectional study was carried out from June 19 to 22, 2020. The study population consisted of children aged 12 to 23 months of which 832 were included. A stratified two-stage cluster survey was carried out. The sources of data were home-based records (HBR), health facility registries (HFR) and parental recalls. Timely vaccination refers to any vaccination that has taken place within 24 h after birth. Descriptive analyzes, the chi-square test and logistic regression were performed.The crude vaccination coverages with BCG, OPV zero dose and HepB-BD were 95.2%, 88.3% and 88.1%, respectively. Vaccination coverages within 24 h after birth were estimated at 13.9%, 30% and 42.1%, respectively. The factors associated with timely HepB-BD are delivery in a health facility , access to television , weighing  and hospitalization of the newborn immediately after birth .Timely administration of birth doses is a challenge in the Podor health district. The solutions would be improving geographic access to health facilities, involving community health workers, raising awareness and integrating health services.The online version contains supplementary material available at 10.1186/s12889-022-12535-z. Vaccination is a preventive act whose objective is to allow the vaccinated individual to benefit from specific protection against an infectious agent before any exposure to it . It is rIn 1974, the World Health Organization (WHO) established the Expanded Programme on Immunization (EPI). WHO recommends that the Bacille de Calmette et Guérin vaccine, the birth dose of oral polio vaccine (OPV-zero dose) and the birth dose of hepatitis B (HepB-BD) vaccine be given at birth, ideally within 24 h after birth . These rAccording to the Global Hepatitis Report published in 2017, 257 million people were living with chronic hepatitis B in 2015, a prevalence of 3.5% . A recenAccording to WHO, 10 to 20 million people of all ages are living with paralytic polio . To dateBy 2030, the WHO estimates that vaccine coverage with BCG and HepB-BD followed by subsequent doses of hepatitis B vaccine reaching 90% should prevent 84% of hepatitis B virus-related deaths  and 115,A Systematic Review and Meta-Analysis showed that in sub-Saharan Africa the pooled coverage rates at day 0–1 after birth were 14.2% (95% CI: 10.1–18.9) for BCG and 1.3% (0.0–4.5) for HepB-BD. No data were available for OPV0 at day 0–1. The rates of vaccine coverage immediately after birth were very low for BCG and HepB-BD, and no data for OPV0 . For popIn Senegal, the tuberculosis incidence rate is estimated at 117 cases per 100,000 inhabitants in 2019. Children aged 0 to 14 years old accounted for 4% of the tuberculosis cases detected in the country [Regarding hepatitis B, Senegal belongs to the group of countries with high endemicity . It has Senegal has implemented the EPI since 1979. In accordance with WHO recommendations, the country has a vaccination policy against tuberculosis, hepatitis B and polio at birth. The HepB-BD has been integrated into the EPI since February 2016 . HoweverAccording to the continuous demographic and health survey carried out in Senegal in 2019 (CDHS-2019), vaccination coverage with BCG, OPV-zero dose and HepB-BD were respectively 94.5%, 80.5% and 81.3%. In the northern zone to which Podor health district belongs, these indicators are respectively estimated at 93.9%, 75.3% and 75.5% . AdminisIt is in this context that this study was undertaken to help fill these gaps. The purpose is to allow the development of guidance notes in terms of strategies for improving vaccination coverage at birth. The objective of this study was to highlight vaccination coverages with birth doses and factors associated with timely vaccination in Podor health district.Vaccination at birth is linked to access and use of health services. Several studies use Andersen RM theoretical model to understand the factors that condition these events . This pr2 [The study took place in Podor health district, which belongs to the eponymous department and Saint Louis region. The health district is located in northern Senegal, in the middle valley of the Senegal River and about 490 km from the Senegalese capital, Dakar. It is bounded to the north by the Islamic Republic of Mauritania, to the south by the health districts of Dahra and Linguère which appear to Louga region, to the west by the health district of Dagana and to the east by the health district of Pété. The health district hosts 247,891 inhabitants. The density is estimated at 35 inhabitants per km2 . Much of2 .It has been established that 45% of the population is in a mobile or advanced zone, that is to say more than 5 km from a health facility . The disIt was a cross-sectional study. Data collection took place from June 19 to 22, 2020. The study population consists of children aged 12 to 23 months. This choice is based on the recommendations of the WHO, which considers that the assessment of routine immunization coverage should relate to an annual birth cohort. Children aged 12 to 23 months are the ideal population for estimating recommended dose coverage between 0 and 11 months. This period concerns not only the three birth doses but also other basic antigens, the last of which is given at 9 months, namely the measles-rubella and yellow fever vaccines. Another advantage is the possibility of estimating the full immunization coverage with this study population .The eligibility criteria are:- Being 12 to 23 months old at the time of the survey;- Having slept in the household the previous night.The sample size is estimated according to the new WHO recommendations .First, the effective sample size (ESS) is calculated as follows:1-α: standard normal distribution evaluated at 1-α = 5%- Z- d: desired half-width of the set confidence interval = 5%- p: expected vaccination coverage rate = 90%- k = 0.51. WHO estimates that when the expected immunization coverage rate is between 0.7 and 1-d, k is calculated using the following formula: k = 4 (p-d) (1-p + d) = 0.51.Thus, the ESS is equal to 216 children aged 12 to 23 months. It corresponds to the number of subjects necessary for a simple random survey.This size will be increased due to the variability between the clusters. To do this, it will be multiplied by a factor called the design effect (DEFF).DEFF = 1 + (m—1) X ICC.- m: number of subjects per cluster equal to 10.- ICC: intra-cluster correlation coefficient fixed here at 1/3.DEFF = 1 + (10—1) X 0.333 = 4.Thus, the minimum sample size = ESS x DEFF = 864. This number is rounded to 870.The number of clusters to select is calculated by relating the sample size to the number of children required for each cluster.Then, a distribution proportional to the size was made to determine the number of clusters required for each health structure.A two-stage cluster sampling was carried out. The survey was stratified according the health facilities. This means that sampling was carried out in each stratum independently. All 39 health facilities were included and each corresponds to a geographical area covering several villages. The first stage corresponds to villages and / or neighborhoods (primary units), the number of which is allocated proportionately according to the size of the geographical area in terms of number of inhabitants. The selection was made according to a simple random survey using the ALEA function of the Excel software. The second stage is made up of households (secondary units). In each village or neighborhood included, households are visited. The first included household is randomly selected from the center of the cluster. Beforehand, a street near the centre of the cluster is drawn at random. The survey started with the first household on the right. The subsequent households are recruited step by step until the required number of children per cluster is reached.A household may not be included due to unavailability or refusal to participate. In this case, it is replaced by the next household. In accordance with the principle of the cluster survey, all eligible children in a household are included.The survey tool was a structured questionnaire designed on the basis of the literature , 32. ItsThe pre-test is carried out on 80 children aged 12 to 23 months living in three parts of Podor city for purposes of inducing interviewers to become familiar with the survey tools. The comments resulting from the pre-test made it possible to finalize the questionnaire which has five sections: i) socio-demographic characteristics of the parents, ii) individual characteristics of the child, obstetric characteristics, iii) knowledge about vaccination, iv) vaccination data according to the home-based records (HBR) or the health facility registry (HFR) and v) vaccination data from vaccination history as recalled by the child’s mothers/caregivers.Twenty-five interviewers were recruited. They were all students. They were given a two-day training course. The first was devoted to the presentation of the target diseases of the EPI, the vaccination schedule, HBR and the HFR. The second day was dedicated to the presentation of the survey objectives, the questionnaire administration method and the collection tools. A round table was made to read the questions. A question-and-answer game followed to further clarify the concepts. Next, the ODK collect application was presented. The teaching techniques used were PowerPoint presentation and role playing.Data collection began after verifying that the child belonged to the age group concerned by the survey. The interviewer determines the exact age of the child based on the date of birth given by the mother / caregiver and the date of the survey. The age is calculated automatically once the date of birth is entered into the tablet.For each eligible child, two data sources are systematically used. The first is the HBR to collect vaccination status and date of vaccination. Investigators are encouraged to take pictures of HBR when they were unable to decipher vaccination dates.The second source is the mother/caregiver statement to assess immunization status only. The questions were worded by describing the sites of administration of the vaccine, namely, the arm, shoulder, thigh and mouth in order to facilitate the understanding of mothers or caregivers.Consultation of the HFR at the child’s usual health care facility is required in one of the following situations: i) the HBR is not available, ii) the HBR is available but information on vaccination is not there or not mentioned, is illegible or is incomplete. To facilitate the use of the HFR, the investigators recorded the first name, last name and date of birth of the child, as well as the first and last name of the mother before leaving the household. This information is sent, using WhatsApp, to the District Medical Officer (DMO) who, in turn, passes it on to the head of the health facility attended by the child. The latter, once the message has been received, checks the vaccination status and the date of vaccination. This data is transmitted to the DMO again and entered into the tablets.Vaccination data relate to vaccination status and date of vaccination. The dependent variable was HepB-BD vaccination coverage within 24 h. The delay was obtained by making the difference between the date of vaccination and the date of birth. It is binary and the modalities are: yes and no. Timely vaccination is one that has taken place within 24 h of birth. Because the time of birth is not marked on the vaccination documents, any vaccination that took place on the day of birth or the next day is considered to have occurred within 24 h after birth.The explanatory variables are those identified and organized using Andersen's theoretical model:Predisposing variables: Mother's age , mother's education , marital status , father's professional status , child’s sex , birth order (1–2 and > 2), knowledge about the age for beginning vaccination , knowledge about the benefits of vaccination , knowledge about co-administration ,Enabling variables: place of residence , distance between residence and health facility , access to newspaper , access to radio , access to television , decision-making about the child's health , family allowance , health insurance , wealth quintile , availability of the HBR , timely initiation of BF , place of delivery , year of birth , season of birth .Need variables: ANC attendance , advice on vaccination during ANC , Hospitalization of the newborn immediately after birth , weighing of the newborn at birth , gestational age , type of delivery , PNC attendance , advice on vaccination during PNC .In accordance with the new WHO recommendations, the inverse probability weighting method was performed for the estimation of crude vaccination coverage with BCG, OPV-zero and HepB-BD. To this end, the probability of including a cluster was calculated. Then, in a given cluster, the probability of including a child is estimated. The product of these two probabilities was used to obtain the probability of selecting a child knowing that the cluster is selected. The reciprocal of this probability is the weight of each child included in the sample .Two types of analyzes were performed. These are descriptive statistics and analytical statistics. The descriptive part made it possible to express the variables as a proportion.Crude vaccination coverage is calculated for each of the three birth doses. This indicator is a proportion. The numerator is the weighted number of children who received the dose. The denominator is the weighted number of children who participated in the survey.The vaccination status of the child is treated as follows: i) if the HBR is available with complete information, then it is valid, ii) if the HBR is not available but the child was in the HFR, then this is valid or iii) if the child does not have a HBR and his name does not appear in the HFR, mother / caregiver recall about the child’s vaccination history is valid.Then, vaccination coverage within 24 h after birth is estimated as a proportion. For this indicator, only the HBR or the HFR are valid. The numerator is the number of children who received the vaccine within 24 h of life. The denominator corresponds to the number of children who received the vaccine regardless of the date of vaccination.The analytical part consisted of investigating factors associated with timely HepB-BD vaccination. The choice made on this dose is explained by the fact that the administration of this dose within 24 h after birth is an indicator of EPI performance . BivariaOf the 870 children aged 12 to 23 months planned, 832 were included, for a response rate of 95.86%.More than one in two mothers or caregivers were between 20 and 29 years old, at 54.7%. The proportion of married was 96.2%. That of children whose fathers were employed was 94.5%. Male children and those in the first or second birth order accounted for 53.0% and 45.2%, respectively.In addition, the proportion of deliveries taking place in health facilities stands at 68.8%. In addition, 84.9% of mothers have attended PNC and 87.7% of children are weighed at birth Table .Table 1BTwo indicators were calculated. Crude BCG, HepB-BD and OPV-zero vaccination coverage were estimated at 95.2%, 88.1% and 89.3%, respectively. In contrast, vaccination coverage within the first 24 h of life was 13.9%, 42.1% and 30%, respectively . In addition, this chance is multiplied by 1.62  and 3.90  when the child is born in a health facility and weighed at birth, respectively. In contrast, a newborn hospitalized immediately after birth has a 58% lower chance of receiving HepB-BD on time  compared to an outpatient newborn  are part of immediate newborn care, while administration of HepB-BD is an essential newborn care . Thus, aHospitalization of the newborn immediately after birth has rightly appeared as a barrier to timely immunization. Two Vietnamese and Italian studies published in 2008 and 2014 respectively highlighted a similar situation , 40. OneHowever, communication should be established between the originating and receiving institution to allow administration of the dose once the newborn is stable .This study found that home birth is a barrier to immunization within 24 h of birth. Three studies from China, Ethiopia and Nigeria illustrate this phenomenon well –43, regaAdditionally, the study found that access to television was positively associated with administration of HepB-BD within 24 h of birth. This result is evocative of the importance of the educational role of the media in public health. More and more people are interested in issues related to their health. Thus, the media are seen as a powerful channel for disseminating information and increasing vaccine awareness and the opinions of vaccine supporters and opponents . This reThe strengths of this study are important to underline. First, the sample size and number of clusters were calculated according to the new WHO recommendations for immunization coverage surveys .Cross-sectional studies are subject to selection and information bias, as well as to confounding factors . In thisThen, the introduction of information bias is mitigated by three strategies. The first is the use of HFR when HBR is unavailable or does not provide accurate immunization status information. The second strategy is to choose a cohort of children aged 12 to 23 months, thus allowing mothers or caregivers to remember the vaccines received. Finally, the training of interviewers and the pre-test of the questionnaire made it possible to harmonize the data collection procedures. Kesmodel US considers that this method is one of the rare solutions to control this type of bias .Confounding factors are a major source of bias . In thisThis study has three main limitations. The first is due to its cross sectional nature, which does not allow a causal relationship to be established between the independent variables and the dependent variable. The second limitation relates to the geographic nature of the study. This was conducted in a single district which may have different characteristics compared to other health districts in the country. Therefore, the generalizability of the results should be viewed with caution. The third limitation is that the time of birth is not mentioned in the HFR. In this case, it is difficult to know precisely whether the child is vaccinated or not within 24 h of birth. The resulting consequence would be the overestimation of immunization coverage within 24 h of birth.This study indicated satisfactory crude vaccination coverage. But those for the 24-h postnatal period are very low. Factors favorable to timely vaccination were access to television, delivery in a health facility and weighing the newborn immediately after birth. In contrast, hospitalization of the newborn immediately after birth was found to be a barrier. Therefore, actions should focus on sensitizing mothers on the importance of immunization at birth using mass media such as television, conducting home visits and pregnancy monitoring by CHWs to administer timely birth doses to home-born children, integrating immunization at birth with essential neonatal care such as weighing, and creating linkages between neonatal immunization services and hospitalization services.In addition, further studies should be conducted to increase knowledge about the facets of birth vaccination.Additional file 1: Table 3. Bivariate analysis of factors associated with HepB-BD vaccination coverage within 24 hours (N = 629), continued. Table 3. Bivariate analysis of factors associated with HepB-BD vaccination coverage within 24 hours (N = 629), continued and end.


There are several methods available in the literature for predicting the insert factor for clinical electron beams. The purpose of this work was to build on a previously published technique that uses a bivariate spline model generated from elliptically parameterized empirical measurements. The technique has been previously validated for Elekta linear accelerators for limited clinical electron setups. The same model is applied to Varian machines to test its efficacy for use with these linear accelerators. Insert factors for specifically designed elliptical cutouts were measured to create spline models for 6, 9, 12, 16, and 20 MeV electron energies for four different cone sizes at source‐to‐surface distances (SSD) of 100, 105, and 110 cm. Insert factor validation measurements of patient cutouts and clinical standard cutouts were acquired to compare to model predictions. Agreement between predicted insert factors and validation measurements averaged 0.8% over all energies, cones, and clinical SSDs, with an uncertainty of 0.6% (1SD), and maximum deviation of 2.1%. The model demonstrated accurate predictions of insert factors using the minimum required amount of input data for small cones, with more input measurements required for larger cones. The results of this study provide expanded validation of this technique to predict insert factors for all energies, cones, and SSDs that would be used in most clinical situations. This level of accuracy and the ease of creating the model necessary for the insert factor predictions demonstrate its acceptability to use clinically for Varian machines. Circular or rectangular shaped fields have established analytical formulas that can be used to calculate the insert factor.One such analytical technique presented by Biggs et al. allows for the calculation of the insert factor for any irregular shape using a bivariate spline model fit to empirically measured output factors.Biggs et al. validated their technique for a 10 cm electron applicator for an Elekta Agility  linear accelerator. The purpose of the current study was to validate the ability of a bivariate spline model to analytically calculate the insert factor for irregularly shaped fields across the range of electron energies and cone sizes for the Varian  Clinac iX and TrueBeam linear accelerators.22.1In our clinic, the MUs for a clinical electron field are calculated using Equation Where:Equation 2.2Empirically measured insert factors for known shapes are used as the basis to create the spline model used to calculate the insert factor for any given irregularly shaped insert. The order of the spline function used requires a minimum of eight data points to create a model. To maximize the ability of the spline model to accurately calculate the insert factor across the full range of insert shapes possible for a given cone size, while also minimizing the number of measurements required, Biggs et al. recommends taking measurements of shapes that bound the range of possible equivalent ellipses that can fit in a given cone. This can be accomplished by measuring multiple ellipses with a length equal to the maximum diagonal dimension of the cone with varying widths, combined with varying diameter circular shapes which represent an ellipse having equal length and width. The insert shapes designed to meet these criteria are illustrated in Table Each insert shape was created in the Varian Eclipse treatment planning system, version 15.6, and a printout of the beams eye view at 100 SSD was used to cut the Cerrobend insert with the Aktina  electron beam cutting and shaping system.The insert factor varies with energy, cone, and SSD. Therefore, a spline model must be created for each electron energy, cone, and SSD combination that could be used clinically, requiring insert factors to be measured for each combination. In our clinic, treatments use electron energies of 6, 9, 12, 16, and 20 MeV with SSDs of 100, 105, or 110 cm.max) for each insert shape must be determined to accurately measure the insert factor. Hence, for each of the inserts, a percent depth dose (PDD) scan was performed to determine the actual dmax for each insert and electron energy. Percent depth ionization (PDI) scans were acquired at 100 cm SSD with the Sun Nuclear  3DS scanning system using a Sun Nuclear 0.125cc ionization chamber. The PDI scans were then converted to PDD using the AAPM TG‐70 protocol in the Sun Nuclear Dosimetry software. The dmax obtained from the PDD scans for each insert was recorded and used for the subsequent ionization measurements. Since the PDD for electron beams does not vary strongly with a change in SSD,max was used for all SSDs.The depth of maximum dose  application was developed to generate the spline model and calculate the insert factor for an irregular insert. The code used to parameterize insert shapes and generate the spline model was the electron factors module in the open‐source Python package PyMedPhys version 0.33.0 made available by Biggs et al.The RT Plan DICOM data created in Eclipse for every insert shape measured in Table To calculate the insert factor for an arbitrary shape, the program reads in an RT Plan DICOM file exported from Eclipse, from which the beam parameters and insert shape are extracted, and then uses the database text file to generate a spline model for the cone, energy, and SSD combination that matches that of the insert. The generated spline model is then used to calculate the insert factor. Finally, the application provides a report of the beam parameters, insert shape, shape parameterization, and the calculated insert factor.2.4To validate the model, insert factor measurements were performed for a sampling of patient inserts that were under treatment, as well as a variety of standard circle and ellipsoid inserts that are used for treatments. A broad range of inserts sizes, beam energies, and SSDs were chosen to validate the model's ability to accurately calculate insert factors across the full range that would be used clinically.Insert factors for the validation inserts were acquired using the same process described in Section 2.2. Patient validation measurements were acquired on a Varian iX, while the standard insert validation measurements were acquired on a Varian TrueBeam.To calculate the insert factors, the clinically used DICOM RT plan data for each patient and each standard insert were exported from Eclipse to the web‐based insert factor program detailed in Section 2.3. The program was run for each patient and each standard insert, and a PDF report was saved of the parameterization and calculated insert factor. An example of the report is presented in Figure 3Tables For the patient cases, the average absolute percent difference between measured and calculated insert factors was 0.9% with a maximum deviation of 2.1% and a standard deviation of 0.8% (1SD). A possible limitation of the validation measurements, which may have led to larger discrepancies between the program's calculations and measurements, is that some of the inserts were not centered about the central axis.For the standard insert validation, the average absolute percent difference between calculated and measured values was 0.6%. The maximum deviation for any case was 1.9%. The standard deviation was 0.8%.The combination of all 42 insert validation comparisons yields a mean absolute difference of 0.8% with a maximum difference of 2.1% and a standard deviation of 0.6%. A histogram illustrating the distribution of the agreement between predicted and measured insert factors is presented in Figure 4The accuracy for the calculation of an insert factor for an arbitrary insert shape demonstrated by the current study compares similarly to previous methods presented in the literature. One dimensional methodology demonstrates an accuracy between measured and calculated insert factors of 2%–3%, pencil beam methods 2%–2.7%, and sector integration methods ranges from 1% to 3%.The results of the current study provide expanded validation on the efficacy of using the bivariate spline model with elliptical shape parameterization for the calculation of insert factors. Biggs et al. validated the technique for 6, 9, 12, 15, and 18 MeV electrons with a 10 cm cone at 100 SSD for an Elekta linear accelerator. In the current study, models were generated and validation measurements were obtained for 6, 9, 12, 16, and 20 MeV for both the Varian iX and TrueBeam linear accelerators for 6 × 6, 10 × 10, 15 × 15, and 20 × 20 cm cones at SSDs of 100, 105, and 110 cm. This validation set covers essentially all possible electron treatments that may be encountered clinically.For clinical treatments involving SSDs other than the modeled 100, 105, or 110 cm, it may be possible to determine the insert factor for an arbitrary SSD by using the insert factors calculated at the three modeled SSDs and interpolating for the insert factor at the desired SSD. Preliminary investigation showed the predicted insert factors follow a quadratic trend, from which a second order polynomial could be fit and used to calculate the insert factor at any SSD within the prediction space. Validation of this technique is a topic of future investigation.One of the main advantages of the technique highlighted by Biggs is the ease of creating the model due to the relatively small number of measurements that are required. The spline model requires a minimum of eight empirical measurements, and the expected uncertainty of the technique to predict insert factors for a 12 MeV beam and 10 cm cone with this number of measurements was estimated as 0.5%.5A previously published technique for the analytical calculation of electron insert factors using a bivariate spline model generated from elliptically parameterized empirical measurements was implemented for Varian linear accelerators. A main advantage of the technique is the ability of models to generate accurate predictions using a minimal amount of input data, with accurate results obtained using only eight data points for the smallest cone and maximum of 11 data points for the larger cones. This study provides expanded validation on the efficacy of using the technique to predict insert factors over the range of electron energy, cone size, and SSD combinations that may be used clinically. Across the range of validation measurements performed, the accuracy of the predicted insert factors was on par with other proposed techniques in the literature, with an average absolute difference of 0.8%, maximum difference of 2.1%, and an uncertainty of 0.6%. Therefore, this methodology can be deemed acceptable for clinical use. It can be reliably used to predict insert factors for any Varian linear accelerator.The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.Both the authors contributed equally to conception and design of the study, acquisition and analysis of the data, and final writing of the manuscript.


Progestogens  are widely recommended for women at high risk of preterm birth. Typical regimens include 17‐hydroxyprogesterone caproate (250 mg intramuscularly weekly), starting at 16–20 gestational weeks until 36 weeks or delivery for women with a singleton gestation and a history of spontaneous preterm birth, or vaginal progesterone  for women with a short cervix . Although some randomized trials support this approach, neither of the largest trials  demonstrated efficacy. There are almost no data on long‐term effects, and none that shows benefit beyond the neonatal period. Although some analyses suggest the cost‐effectiveness of the approach, a cervical length screening program followed by progesterone for those with a short cervix will reduce preterm birth rates by less than 0.5%. The present review assesses evidence on the efficacy, likely impact, and long‐term effects of implementing the recommendations for progestogens in full. Clinicians and pregnant women can look forward to resolution of the conflicting views on efficacy once the Patient‐Centered Outcomes Research Initiative (PCORI)‐funded individual patient data meta‐analysis is published. The efficacy, probable impact, and long‐term effects of progesterone or 17‐hydroxyprogesterone acetate on the prevention of preterm labor are uncertain. This can be done at the same time as the ultrasound performed for the anatomical survey  diagnosed in the mid‐trimester should be offered daily vaginal micronized progesterone treatment for the prevention of preterm birth and neonatal morbidity.”“The progesterone formulation to be used is vaginal micronized progesterone  nightly or vaginal micronized progesterone gel (90 mg) each morning.”“Universal cervical length screening and vaginal progesterone treatment  is a cost‐effective model for the prevention of preterm birth.”“In cases in which a transvaginal ultrasound is not available, other devices may be used as a screening tool to measure objectively and reliably the cervical length.”The importance of progesterone in the maintenance of pregnancy is well established and applies across many species. Indeed, the term “progesterone” is derived from the phrase “progestational steroidal ketone.” In 2015, the International Federation of Gynecology and Obstetrics (FIGO) working group on the best practice in maternal fetal medicine published a guideline endorsing the use of progesterone to prevent preterm birth for selected women.The aim of the present review is to discuss the rationale for these recommendations, their likely impact, and whether they should be updated in the light of new evidence.2Progesterone clearly plays a role in the maintenance of pregnancy. Circulating levels of progesterone rise during pregnancy: the major source (in humans) is the corpus luteum until approximately week 8 of pregnancy, and the placenta thereafter. One of the major mechanisms of progesterone action in maintaining pregnancy is inhibition of the contractions of the myometrium: research has demonstrated the relaxant effect of progesterone on myometrial strips in vitro.The importance of progesterone in maintaining human pregnancy in vivo has been demonstrated by studies administering receptor antagonists such as mifepristone (RU486). If administered in early pregnancy, mifepristone increases uterine contractility in vivo,So, what is the evidence on which the FIGO recommendations for progesterone prophylaxis in women with a short cervix are based? To address this question, it is necessary to consider the efficacy of progesterone, the impact of such a strategy on a population basis, and the long‐term benefits and harmful effects of progesterone treatment in pregnancy.3The most recent Cochrane review on progesterone for the prevention of preterm birth (published in 2013) examined evidence on the use of any progestogen for women at risk of preterm birth either because of a previous preterm birth or because of a short cervix.For women with cervical shortening the review found that, among the above outcomes, only preterm birth before 34 weeks was reduced by progestogen .Further analyses in the review found no differential effects in terms of route of administration, time of commencement of therapy, or dose of progesterone for the majority of outcomes examined.+0 and 20+6 gestational weeks, and continued until 37 weeks or delivery (whichever is earlier). Supporting evidence for the licensing of intramuscular 17‐hydroxyprogesterone caproate were provided by the trial of Meis et al.Importantly for clinicians and for pregnant women, the regulatory status of the different progestogen formulations given for preterm birth differs. Intramuscular 17‐hydroxyprogesterone caproate (Makena) is licensed by the US Food and Drug Administration (FDA), but not the European Medicines Agency (EMA), to reduce the risk of preterm birth for women with a singleton pregnancy who have a history of singleton spontaneous preterm birth. The product license refers to a dose of 250 mg, administered intramuscularly once per week, starting between 16+0 to 20+6 gestational weeks until 37 weeks or delivery (whichever is the earliest). The two co‐primary efficacy endpoints were preterm birth before 35 gestational weeks and a composite index of neonatal morbidity and mortality.Although the FDA provided a license, a component of approval was the requirement for a confirmatory trial.The results of the PROLONG study were published in October 2019.Commentators have had a mixed reaction to publication of the PROLONG study. The FDA advisory committee has suggested that 17‐hydroxyprogesterone acetate should be withdrawn from the market for the prevention of preterm delivery, although this decision has not yet been finalized. The American College of Obstetricians and Gynecologists (ACOG) and the Society for Maternal and Fetal Medicine (SMFM) have both noted that women enrolled in the PROLONG trial were at lower risk for preterm birth as compared with those in the trial of Meis et al.+0 to 23+6 gestational weeks were randomized either to vaginal progesterone (90 mg) or placebo. The primary outcome was delivery before 33 weeks, and 235 and 223 women were available for follow‐up in each group. The progesterone group showed a significant reduction in the rate of preterm birth before 33 gestational weeks  and in neonatal outcome as a composite of adverse events . Among the individual components of neonatal outcome, only a reduction in respiratory distress syndrome was statistically significant .In contrast to 17‐hydroxyprogesterone caproate, vaginal progesterone is not licensed for preventing preterm birth in the United States. A submission to the FDA was prepared from data generated by a large randomized trial conducted in the United States and elsewhere.Having reviewed the data from that study, the FDA chose not to provide a license for vaginal progesterone for preterm birth prevention. The FDA notes accompanying their decision state: “the statistical test used by the ‘applicant’ was inappropriate because of insufficient sample size in each strata and inconsistent treatment effects within strata,” that “the first dose, maternal age, cervical length, body mass index, and race differed notably by region,” and that “after adjusting for these covariates, the effect of progesterone in reducing preterm birth was not statistically significant”.improve obstetric outcome by lengthening pregnancy and thus reducing the incidence of preterm delivery (before 34 weeks);improve neonatal outcome by reducing a composite of death and major morbidity;lead to improved childhood cognitive and neurosensory outcomes at 2 years.Two large studies published since the Cochrane review in 1913 did not find a positive effect of progesterone in preventing preterm birth. For women at high risk of preterm labor, the OPPTIMUM study+0 and 24+0 gestational weeks, combined with a history in a previous pregnancy of any of the following: preterm birth, second‐trimester loss, premature fetal membrane rupture, or a cervical procedure to treat an abnormal smear test. In addition, women with a history of a previous spontaneous preterm birth before 34+0 weeks and those with a cervical length of 25 mm in the index pregnancy were eligible regardless of the fetal fibronectin test result.The double‐masked placebo‐controlled randomized OPPTIMUM trial was conducted among 1228 women at high risk of preterm birth at 65 UK National Health Service (NHS) hospitals and one Swedish hospital between February 2009 and April 2013.P values for the three primary outcomes are summarized in Table The odds ratio (OR), 95% CI, and P=0.912).Subsequently, the PROGRESS studyThus, there are clearly conflicting data about the efficacy of progesterone for preterm birth prevention.To address this controversy, the Patient‐Centered Outcomes Research Initiative (PCORI) has commissioned a prospective, independent comprehensive, high‐quality, individual patient data meta‐analysis on the efficacy of progesterone for preterm birth prevention. Researchers from all studies evaluating the efficacy of progestogens for preterm birth prevention have been invited to submit their data. The results are expected in early 2020, and it is likely that this project will give the most authoritative estimates of the efficacy of progesterone for preventing preterm birth and its consequences for women at high risk.4Many groups have evaluated the cost‐effectiveness of routine cervical length scanning to identify women with a short cervix, combined with prescribing progesterone for preterm birth prevention.The overall analysis suggested that a policy of routine cervical length scanning  combined with progesterone prophylaxis for 0.85% of women with a short cervix would be cost‐effective in the United States. It would require 2.19 million vaginal sonograms, and the prescription of vaginal progesterone for 11 027 women annually; however, there would be 913 fewer preterm births and 63 fewer neonatal deaths. The total cost would be US $52 million annually. Given the costs accruing from adverse outcomes due to prematurity, the “no screen” option was most expensive. Risk‐based screening was the least expensive option, but universal screening was most cost‐effective, with an incremental cost‐effectiveness ratio of US $21 144 per quality‐adjusted life year.Regardless of its cost‐effectiveness, the impact of universal cervical length screening on the rate of preterm births is trivial in the context of the overall preterm birth rate. In 2014, there were 381 659 preterm births in the United States; thus, prevention of 913 births would reduce the rate of preterm birth from 9.57% to 9.55%. Performing a similar analysis in France, Rozenberg has described this as the inverse of the Pareto principle—in other words, a large amount of effort for a small gain.There are other challenges in providing universal cervical length screening. The sonogram “cost” of US $73.47 described above probably does not include training, quality‐control programs, or equipment. In addition, without extensive training of additional providers, there will be insufficient availability of cervical length scanning to perform this analysis on a population basis. Furthermore, reproducibility is limited even when experienced observers perform measurements under standardized conditions.5Clinicians and pregnant women wishing to use progesterone to prevent preterm birth need to be aware of the long‐term risks and benefits. The primary rationale for preventing preterm birth is to avert adverse consequences for the newborn. Worldwide, 15 million preterm births per annum result in around 2000 neonatal deaths, and neurodevelopmental disability in nearly 1 million survivors.A good example of this is the ORACLE II randomized trial of antibiotics to prevent preterm birth among women presenting with signs and symptoms of preterm labor, but with intact fetal membranes. Although there were no major differences in outcome in the short term ,P=0.087).Regarding singleton pregnancy, only two studies have examined the long‐term effect of progestogens. The follow‐up to the study of 17‐hydroxyprogesterone caproate by Meis et al.66 gestational weeks receive 17‐hydroxyprogesterone caproate (250 mg intramuscularly weekly) starting at 16–20 weeks until 36 weeks or delivery for women with a singleton gestation and a history of prior spontaneous preterm birth.The National Institute of Clinical Excellence in the United Kingdom,As discussed in this review, however, the evidence on efficacy for those at risk of preterm birth, impact on preterm birth rates, and long‐term effects for the baby of implementing these recommendations remains inconclusive. Clinicians and pregnant women can look forward to some resolution of the conflicting views on efficacy once the PCORI‐funded individual patient data meta‐analysis is published. Recommendations should be updated once the full details of the PCORI individual patient data meta‐analysis is in the public domain.JN wrote and revised this article, and is responsible for the final version.The author has received funding from government and charities for research on preterm birth, stillbirth, and obesity in pregnancy. She is on a Data and Safety Monitoring Committee for GlaxoSmithKline for a trial of an agent to treat women in preterm labor, was the Chair of the NICE guideline development committee on Preterm Labor and Birth (pub. Nov 2015), and received funding from NIHR for the OPPTIMUM study of progesterone for the prevention of preterm birth.


The hydatid cyst is a worldwide anthropozoonosis, which constitutes a health issue in Northern Africa. It may involve any organ, but it mostly affects the liver. This often asymptomatic disease can lead to multiple complications. Among them, spontaneous fistulization of a hepatic hydatid cyst in the stomach is exceptional even in endemic countries. We report the case of a 38-year-old female with febrile biliary colics due to a hydatid cyst of the liver fistulized in the stomach. The diagnosis was established based upon different clinical, biological and mainly radiological features. She received surgical treatment with satisfactory postoperative outcome. We report the case of a 38-year-old female with no prior medical history, no comorbidities nor allergies. She presented to the emergency room with a 3-month history of isolated biliary colics. She experienced worsening of the symptoms 1 week prior, with the onset of intermittent fever and vomiting containing membranes. Physical examination found a patient with vital signs within the normal range aside from mild tachycardia, a fever of 38.5°C , no conjunctival pallor, and normally colored urine and stools. Abdominal examination was notable for a distended abdomen and right hypochondrium tenderness. The rest of the physical examination was normal. Laboratory analysis found high levels of C-reactive protein at 240 mg / l  and normal white blood cell count at 10,000/mm3 . Cholestasis assessment was normal: total bilirubin at 4.2 mg / l  with a unconjugated fraction at 1.7 mg / l , aspartate aminotransferase at 37 IU / l , alanine aminotransferase at 30 IU / l .All the causes of gallstones complications (acute cholecystitis and cholangitis), liver abscess, pancreatitis but also causes of febrile right upper quadrant abdominal pain : pyelonephritis, subhepatic appendicitis, or even right basal pneumonia.On the erect plain abdominal film, there was an abnormal extra luminal gas collection in the epigastric region . An abdoA computed tomography scan of the chest and abdomen was performed with intravenous contrast demonstrating a cystic mass within the left liver lobe parenchyma, with an air fluid level, well-defined and thick capsule, compressing the stomach. Further assessment revealed a close contact with the gastric wall and an air filled communication track with the cyst.In addition we observed mass effect on the splenic vein resulting in many collateral vessels and a markedly dilated coronary vein. The CT also revealed coelio mesenteric lymphadenopathies .Finally, there was no pulmonary or mediastinal abnormalities on the chest CT examination.We then chose complete the CT examination with oral contrast to confirm the presence of an abnormal communication between the liver mass and gastric lumen. It showed the contrast delineating a fistula track between the stomach through the lesser curvature wall and the cyst .The patient underwent a laparotomy, finding an enormous multilocular hepatic hydatid cyst adherent to the gastric wall. Cystic exploration found of a fistula between the cyst and the stomach .A nasogastric tube was placed, and aspirated purulent fluid containing membranes, suggesting the presence of a fistula. A resection of the protruding dome was performed with a gastric wedge resection and the stomach defect was sutured. Finally a surgical drain was placed in the residual cavity.Post-operative outcome was satisfactory and the patient was discharged after 3 weeks.1,2 the most common site of perforation being the stomach. To the best knowledge of the other no case report of this nature has been reported.Fistulization of the hydatid cyst in the gastro intestinal (GI) tract is extremely rare even in highly endemic countries.,3–5According to surgical records of hepatic hydatid cysts: 0.29% were ruptured into the gastrointestinal tract and 0.15% into the duodenum. In a multicentric study conducted by Zaouche on hydatid cyst complications in 1994, only 3 cases were ruptured into the hollow viscus.It is believed that hydatid cyst communication with the bowel lumen depends on : cyst location, infection and close contact.3,4Communication between the hydatid cyst and any part of GI tract  is more likely to occur when the cyst is located on the inferior surface of the liver.Also, infection of the cyst with the thickening of its walls may create adhesions between the cyst and the surrounding organs.Moreover, continuous friction by the thickened or calcified cyst results in bowel wall erosion.These last two conditions were met in our patient .On the other hand, this complication is known for its clinical polymorphism ranging from abdominal discomfort to pain, or fever.6Typically, the presence of membranes in the stools “hydatidorrhea” or in the vomit “hydatidemesis” are highly suggestive.In our case, the patient presented with biliary colics, fever and hydatid vomiting.Although this complication is hardly ever diagnosed pre operatively, imaging appears to have a key role in making the diagnosis.Because of its availability and simplicity, ultrasound is the first imaging technique used in an emergency setting.7It helps characterize the cystic nature of the lesion and the Gharbi classification which remains the first and most widely used classification, particularly for ultrasound.8The imaging findings of hydatid disease vary according to its stage of development, ranging from cystic lesions to a completely solid mass. The classification of Gharbi is currently replaced by the World Health Organization (WHO) classification, useful in deciding the appropriate management depending on the stage of the cyst on ultrasound.There is a correspondence between the two classifications. The cystic echinococcus (CE) one cyst refers to a simple cyst (Gharbi Type I). The CE2 stage consists of a multi vesicular cyst, containing septations, described as a “rosette” or a “honeycomb” sign (Gharbi Type III). This appearance is pathognomonic.9–11The CE3 cyst contains a daughter cyst within the encompassing parent cyst. The daughter cyst can have detached laminated membranes, giving a “water lily” sign (Gharbi Type II). The CE4 stage has a mixed hypoechoic and/or hyperechoic matrix, with no daughter cysts (Gharbi Type IV). The CE5 cyst is characterized by a thick partially or completely calcified wall (Gharbi Type V). Ultrasound classifications can be extrapolated to computed tomography and magnetic resonance imaging.Cross-sectional imaging appears to be essential in the event of complications particularly for the preoperative assessment.CT scan plays a major role, showing a cystic lesion of the liver commonly on the inferior surface, with signs of infection like thickening and enhancing wall, containing an air fluid level, and responsible for a mass effect and very intimate contact with the stomach.6,12Oral contrast administration makes it easier to visualize the fistula between the cyst and the stomach, demonstrated by the passage of the iodine from the stomach to the cyst.This examination protocol was the key to make the diagnosis in our case.13However, the fistula is not always visualized, often related to hydatid membranes obstructing the communication, in which case the diagnosis is only made in the operating room.Currently, surgery is the standard treatment for complicated cysts as well as extensive, large and symptomatic uncomplicated cysts.10Preoperative medical treatment with albendazole is recommended because it decreases the viability of the cysts. There is little specific data on the benefits of postoperative or perioperative use of medical treatment. But most authors agree on the effectiveness of postoperative medical treatment in reducing the risk of recurrence.Being an emergency surgery in our case, the patient did not receive premedication.Hydatid cyst is a worldwide anthropozoonosis. It mainly affects the liver and presents several complications dominated by fistulas and infection. Fistulization in the bowel lumen remains exceptional and is dominated by fistulization in the stomach.Imaging is essential for correct and appropriate diagnosis of gastric cyst fistulization and to avoid treatment delays. The key examination is computed tomography with oral contrast, making it easy to visualize the gastric fistula. Treatment is mainly surgical.Early diagnosis and surgical treatment of complicated and symptomatic intra abdominal hydatid cysts reduces morbidity and mortality.


The development of motor function is related to the development of neural pathways in the white matter. Children with developmental delay (DD) and hypotonia have reduced motor function, and their neural pathways are observed differently from those of typically developed children. We investigated changes in neural pathways through diffusion tensor imaging (DTI) after utilizing the Vojta approach. The participant was a child with DD and hypotonia, and had delayed motor function. Although he had no brain damage on magnetic resonance imaging findings, damage to the neural pathway was confirmed through DTI due to cytomegalovirus infection in the mother’s womb. From 11 months of age, the Vojta approach was performed for a total of 8 months. In this study, we found that in CST, the left FA and right TV increased in follow-up DTI more than in the initial DTI. In CRP, Wallerian degeneration was observed in the left FA, MD, and TV in follow-up DTI. GMFM-88 improved after intervention. The structural change of neural pathways through the Vojta approach influenced the improvement of gross motor function. Therefore, it is thought that the Vojta approach can be suggested as a meaningful intervention for children with DD and hypotonia. The Vojta approach induces a certain movement by stimulating specific stimulation zones. It is a method that suppresses abnormal movement, and induces normal motor development by repeatedly memorizing the normal movement in the brain . These sDD and hypotonia are diseases that cause problems due to interference with normal brain development at the time of brain formation, or after birth . This inThe development of motor function is related to the development of neural pathways . The neuDiffusion tensor imaging (DTI) is a method for evaluating the structure of these neural pathways, which is an effective test for studying the fundamental structure of white matter . DTI is Among the various intervention methods, the Vojta approach is reported to be effective in improving the motor function of children with DD and hypotonia , but stuThe participant was a male, born on 19 April 2016, with a gestation period of 39 weeks and 4 days, and a birth weight of 2.6 kg. At birth, his heart rate decreased, and autonomous respiration was difficult, so oxygen therapy was given for 10 days. MRI showed no brain damage. Thereafter, he was discharged from the hospital and lived at home, and there were no special features in sleep, diet, and other lifestyle patterns. However, he had difficulty in head control and eye contact until approximately six months of age, and was diagnosed with DD at the hospital in October 2016.In February 2017, there was no progress in motor development, so he underwent a thorough examination at the hospital. As a result, the child was diagnosed with cytomegalovirus infection transmitted from the mother in utero. He was hospitalized for approximately one month for cytomegalovirus treatment, and was discharged after completion of treatment. While in the hospital, he underwent an initial DTI at 10 months of age, which confirmed damage to his neural pathways. He also had hearing problems. He was discharged in early March 2017, and was able to control his head and roll over at the time. The child received the Vojta approach from early March 2017, after his hospital discharge. A follow-up DTI was performed after 9 months. The goal of rehabilitation for the child and parent involved was to enable normal motor development and participation in daily life through early intervention. We informed the child and parent of the purpose of the study, and they consented to this study. This study was approved by the Research Ethics Committee of Kyungnam University (1040460-A-2020-055).DTI was used to measure the neural pathway changes before (10 months of age) and after (18 months of age) intervention application. Since the child was young and unable to follow the examiner’s verbal instructions, the child was tested after taking a sleep-inducing drug to limit movement during the measurement.2; TE = 76 ms; TR = 10.726 ms; SENSE factor = 2, EPI factor = 67; b = 600 mm2 s−1; NEX = 1; and a slice thickness of 2.3 mm. Pre-processing of the DTI data set was performed using the Oxford Centre for Functional Magnetic Resonance Imaging of the Brain (FMRIB) software library (FSL), and DTI Studio software  was used for reconstruction of CST and CRP.The DTI data were acquired using a Synergy-L Sensitivity Encoding (SENSE) head coil on a 1.5 T Philips Gyroscan Intera , and single-shot echo-planar imaging (EPI). For each of the 32 non-collinear and non-coplanar diffusion-sensitizing gradients, we acquired 60 contiguous slices parallel to the anterior commissure–posterior commissure line. The image parameters were as follows: matrix = 128 × 128; field of view = 221 × 221 mmThe fiber tracking was performed using a fractional anisotropy (FA) threshold of >0.15 and direction threshold of <70°. The three-dimensional fibers were superimposed on the T2 transverse images performed immediately after DTI imaging. We measured the FA, mean diffusion (MD), and tract volume (TV) of CST and CRP in both hemispheres .The Gross Motor Function Measure-88 (GMFM-88) is a standardized evaluation tool that can evaluate changes in gross motor function and the effects of treatment . The iteIntervention was performed by physical therapist. The Vojta approach consists of reflex turning 1, reflex turning 2, and reflex creeping. Reflex turning 1 and reflex turning 2 target the quadrupedal position by stimulating specific zones, and the reflex creeping induces forward movement from the prone position. The intervention was applied for 40 min per session, 3 times a week, for a total of 8 months. It consisted of 10 min each, depending on posture, a total of 30 min, and stretching was performed for 5 minutes before and after the intervention.In the CST, the right FA decreased at follow-up rather than at the initial intervention, but the left FA increased at follow-up rather than at the initial intervention. The right and left MD decreased at follow-up rather than at the initial intervention. The right TV increased at follow-up rather than at the initial intervention, but the left TV decreased at follow-up rather than at the initial intervention.In the CRP, the right FA decreased at follow-up than at the initial intervention, but the right MD and TV increased at follow-up rather than at the initial intervention. The left FA, MD, and TV showed degeneration at the initial intervention  Table 1Table 1. In the GMFM-88 scale, gross motor function improved from 17.17% at initial intervention to 57.35% at follow-up .Myelination of white matter is closely related to the development of sensory, motor, and cognitive functions in children ,24, and The development of the CST affects the prognosis of motor function . Azizi eThe CRP exhibits symmetrical integrity during normal motor development, but if disruption occurs, it cannot be considered normal development . As a reThe limitation of this study is that it is a single case report, and it is difficult to generalize the results, since there is only one participant. Furthermore, there was no control group, so it was difficult to compare the results. In addition, it was difficult to perform various functional evaluations due to the young age of the subject. Therefore, in future work, studies that complement these limitations should be conducted.We were able to objectively prove the effect of the Vojta approach on the improvement of gross motor function by observing neural pathway changes using DTI in a child with DD and hypotonia.


Breast pseudoaneurysm is a very rare complication. In this study, we report a patient with huge breast pseudoaneurysm after ultrasound-guided vacuum-assisted biopsy (UGVAB) of breast nodules. In treatment, we used microwave ablation to treat the pseudoaneurysm, and then used UGVAB again to eliminate the complicated hematoma. The patients obtained good therapeutic effect. From this case, we experience that, before the interventional operations for breast nodules, the systematic ultrasound examination should be performed. In the needle entering channel, the obvious blood vessels should be avoided to reduce the unnecessary vascular injury. When the pseudoaneurysm occurs, the patient’s condition, pseudoaneurysm situation and hematoma size should be comprehensively considered, combined with the multidisciplinary consultation, for selecting the best treatment strategy. Pseudoaneurysm often occurs in the main and middle arteries. The most common sites of traumatic pseudoaneurysm are the femoral artery, carotid artery, ulnar artery, etc..A 48 year-old woman was found with multiple nodules in her breasts during the routine physical examination. The patient came to our hospital, and asked the minimally invasive treatment of two larger nodules. Under the ultrasound guidance, the UGVAB was performed using the 9-guage rotary cutting needle. The histopathology showed the breast sclerosing adenosis combined with reactive lymph node hyperplasia in the right-side mass and breast fibroadenoma combined with local acute and chronic inflammatory cell infiltration and micro abscess in the left-side mass. On the third day after the surgery, the patient came back to the hospital. She complained that, after the removing the bandage at postoperative 48 hour, there was a mass in the right breast. The mass then became larger and larger, and the pain became more and more serious. When she arrived at the hospital, she was difficult to lift the right hand up. The conventional ultrasound examination showed an uneven hypoechoic mass (about 6.7 cm * 3.5 cm * 5.3 cm) in the right upper breast quadrant, with a pulsatile dark area (about 1.1 cm * 0.7 cm * 0.5 cm) at the inner edge . The colIn the treatment of pseudoaneurysm, the commonly used methods included the ultrasound-guided local directional compression, percutaneous prothrombin injection,The most common complications of UGVAB are the hematoma and infection. At present, hematoma is the main complication found in our hospital, which can be spontaneously absorbed in 3-6 weeks. The vascular injury is a rare complication of UGVAB. It has been reported that, the incidence of pseudoaneurysm is very low in iatrogenic injury.From this case, we obtain some experiences for breast pseudoaneurysm. Before the interventional operations including core needle biopsy and UGVAB, the systematic ultrasound examination should be performed. In the needle entering channel, the obvious blood vessels should be avoided, so as to reduce the unnecessary vascular injury. When the pseudoaneurysm occurs, the patient’s condition, pseudoaneurysm situation and hematoma size should be comprehensively considered, combined with the multidisciplinary consultation, for selecting the best treatment strategy.