The effect of live birth/parity number on incident hypertension was investigated among Iranian parous women aged 30–70 years. The study population included 2188 normotensive women who were enrolled in 1999–2001. They were followed for incident hypertension (based on JNC 7 report) by 3‐year intervals up to April 2018. Multivariable Cox proportional hazard models, adjusted for a wide set of potential hypertension risk factors, reproductive factors, and pregnancy complications, were applied to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of the number of parity/live birth(s) for incident hypertension. Additionally, as a sensitivity analysis, age‐scale Cox regression was also done. During a median follow‐up of 13.5 years, 935 incident hypertension have occurred. Compared to those with two live births, the participants who had 3 and ≥4 live births were at higher risk of hypertension development by the HRs of 1.25 [95% CI: 1.02–1.55] and 1.39 [1.12–1.72], respectively, in the full‐adjusted model. Moreover, each additional live birth increased the risk of hypertension by a HR of 1.06 [95%CI: 1.02–1.11]. Results of parity number were also similar. Considering age as time scale also did not change the results generally. The authors found a significant interaction between live birth/parity number and age groups; the adverse effect of higher live birth/parity numbers on hypertension development was mainly found among those aged < 50 years. To sum up, compared to the live birth/parity number of two, Iranian women with ≥3 live birth/parity had a higher risk of incident hypertension; the issue was more prominent among younger mothers. Most of these hypertensive cases live in low‐ and middle‐income countries.In addition to known hypertension risk factors such as aging, dietary factors , obesity, lack of physical activity, and other potential hypertension risk factors,Most of the previous findings of the effect of live birth and parity on BP level or hypertension were limited to cross‐sectional studies with inconsistent results. Although some previous studies suggested that parity can have lowering effects on BP level,The current study aims at determining whether the live birth/parity number is an independent risk factor for hypertension development among Iranian women aged 30–70 years, with 13.5 years of follow‐up, using a population‐based cohort, the Tehran Lipid and Glucose Study (TLGS).22.1The TLGS is a prospective cohort study. This study was conducted on a representative sample of Tehranian citizens that resided in district 13 of Tehran. Determining the prevalence, incidence, and other epidemiologic aspects of non‐communicable diseases (NCDs) and also prevention of NCDs by advancing healthier lifestyles were the original aims of the TLGS. The details of the design, measurement methods, and enrollment strategy of the TLGS have been described elsewhere.n = 243), and no follow‐up measurement (n = 409), remaining 2188 eligible women to follow‐up to April 2018.Among a total of 4283 female participants aged 30–70 years, 153 single women, and eight married women with no live birth were excluded. We also excluded 1212 patients with prevalent hypertension and 70 patients with prevalent CVD at baseline, leading to 2840 women. Other reasons for exclusion were missing data on parity/live birth number and other covariates  was calculated as weight in kilograms divided by the square of height in meters. We also measured waist circumference (WC) at the level of the umbilicus with light clothing. Subsequent to 15 min of rest, using a standardized mercury sphygmomanometer , BP measured two times by a trained physician on the right arm in a sitting position in the TLGS office. The mean of these two office BP measurements was considered as the patient's BP. After at least 12 h of fasting, morning blood samples were collected from all participants. Measurements of fasting plasma glucose (FPG), triglycerides (TG), and high‐density lipoprotein cholesterol (HDL‐C) were performed by standard and validated methods, as explained before.2.3Main exposure: The sum of the number of live birth and the stillbirth (defined as the birth of an infant which died in the mother's uterus after 20 weeks of gestation) was considered as parity number.Confounder factors: Diabetes mellitus (DM) was defined as a FPG level of ≥7.0 mmol/L or pharmacologically treated with glucose‐lowering drugs. Smoking status was categorized into two groups; current smokers versus former/never smokers. Prior diagnosed CVD in female first‐degree blood relatives aged < 65 years or male first‐degree blood relatives aged < 55 years was defined as a positive family history of premature CVD. Based on the World Health Organization's definition, the absence of spontaneous menstrual bleeding for more than 12 months, without other pathologic or physiologic cause could be determined as menopauseOutcome: Based on the seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high BP (the JNC 7 report), hypertension, whether at baseline or as an outcome during follow‐up, was defined as the presence of at least one of the following criteria: (a) having SBP≥140 mm Hg, (b) having DBP≥90 mm Hg, and (c) initiation of anti‐hypertensive drugs usage. Moreover, SBP 120–139 mm Hg or DBP 80–89 mm Hg were defined as prehypertension.2.4Descriptive statistics were used to describe baseline characteristics as mean ± standard deviation (SD) for normally distributed continuous variables, median (interquartile range: IQR) for the highly skewed variables, and number (%) for categorical variables. We compared the baseline characteristics of the participants across the number of live birth  using chi‐square, fisher's exact, ANOVA, and Kruskal–Wallis tests as appropriate.The time to event was described as the time of censoring or the outcome occurring, whichever firstly came. In the case of death, leaving the district, or being until the end of study phase VI (April 2018) without any event, we censored participants. For individuals with incident hypertension, the event date was defined as the mid‐time between the dates of the follow‐up visit at which a patient developed hypertension and the last follow‐up visit preceding incident hypertension.Cox proportional hazard models were used to evaluate the association of parity and live birth number with incident hypertension. Parity and live birth number were considered as both continuous and categorical variables in the Cox models, separately. We considered live birth/parity number of two as the reference group, given that this number was associated with the lowest risk for CVD event among Iranian women.p‐values for interaction were lower than .02), HRs with 95% CIs were reported for each subgroup of age separately.Since the effect of parity/live birth number on BP might be differed by menopausal statusp‐value ≤.05 was considered significant.Using the Schoenfeld residual test, the proportionality was assessed for the Cox models. All proportionality assumptions were appropriate in this study. STATA version 14  statistical software was used for statistical analyses of the current study and a two‐tailed 3The study population consists of 2188 female participants with a mean age (SD) of 43.64 (9.53) years. The baseline characteristics of the study population according to the number of live birth are presented in Table During a median follow‐up of 13.58 years (IQR:7.36–15.94), 935 incident hypertension have occurred. As shown in Figure p‐value: .056], and significant for parity number of ≥4 (1.24 [1.01–1.52]) in model 4 . Moreover, after adjustment for a wide series of confounders in model 2, compared to the reference group (live birth/parity number = 2), having 3 and ≥4 live birth/parity(s) increased the risk significantly; even with the further adjustment of prehypertension, preeclampsia and GDM, the association remained marginally significant for live birth number of ≥4  increased the risk of incident hypertension significantly in model 4 (1.05 [1.01—1.10] for live birth number and 1.05 [1.01–1.09] for parity number). Moreover, after excluding these 133 participants, our results for women without having other delivery after baseline were similar to main analysis Table .p‐values > .05). On the other hand, live birth/parity number, whether as continuous or categorical variables, had a different effect on hypertension development in < 50‐year and ≥50‐year participants . Multivariable HRs and 95% CIs in different subgroups of age are shown in Figures The interaction of menopausal status and live birth/parity number  was non‐significant ; however, due to cross‐sectional design of this study, their finding was not comparable with our prospective results.Based on a study on perimenopausal and postmenopausal women from Italy, Giubertoni and coworkers found that compared with nulliparous women, those with at least one child had higher prevalence of hypertension; however, the incidence of hypertension during follow‐up was not related with parity.The observed higher hypertension risk and prevalence by increasing in live birth/parity number was suggested to be mainly attributed to the pathway of metabolic changes  that occur during pregnancy physiologically.n = 8) to compare the impact of nulliparity with ever parity. Third, we relied on office BP measurements using non‐automated device rather than ambulatory or home BP measurements; hence, we cannot diagnose those with “white coat” hypertension or “masked” hypertension. However, the method applied in other population‐based studies.The key strengths of this study are its long duration of follow‐up, standardized measurements for confounders and outcome rather than relying on self‐reported data, and using a wide set of confounders, especially complications of pregnancy that poorly addressed in previous studies. However, several important limitations need to be considered. First, no access exists for valid data on job status, income, and diet habits of participants. These factors can be the socioeconomic and lifestyle factors that have a potential effect on hypertension development. Second, the number of female participants with no children at baseline was too low (To sum up, during more than a decade of follow‐up, among residents of the metropolitan city of Tehran, compared to live birth/parity number of two, those with ≥3 live birth/parity had higher risk of incident hypertension, independent of well‐known hypertension risk factors and reproductive factors; the issue was more prominent among younger mothers. Further investigations are needed to evaluate this issue in other parts of the country and also discover the potential role of socioeconomic and lifestyle factors in the pathway between live birth/parity and hypertension development.There are no conflicts of interest.Study conception and design: Seyyed Saeed Moazzeni and Farzad Hadaegh; Analysis and interpretation of data: Samaneh Asgari and Farzad Hadaegh; Drafting of the manuscript: Seyyed Saeed Moazzeni and Farzad Hadaegh; Critical revision: Fereidoun Azizi and Farzad Hadaegh. All authors read and approved the final manuscript.Supporting materialClick here for additional data file.Supporting materialClick here for additional data file.Supporting materialClick here for additional data file.


An omental cyst is a rare intraabdominal pathology that can cause acute abdomen and intestinal obstruction among children. A 2-year-old boy presented with fever, bilious vomiting, abdomen distension and loose stool of acute onset. The chest and abdominal radiographs showed right pleural effusion and prominent small bowels with thickening walls respectively. Ultrasonography revealed a gastrointestinal duplication cyst. An exploratory laparotomy was done and found a 5x5 cm infected omental cyst, severely adhered to and eroded into the ileum causing a small perforation. Omental cyst excision and ileal primary repair were done. The final diagnosis was a benign omental cyst. Omental cyst is usually asymptomatic; however, symptomatic omental cyst should be cautious for bleeding, intestinal obstruction, infection, torsion and rupture. An omental cyst is an uncommon intraabdominal pathology. It can mimic acute abdomen and intestinal obstruction among children in complicated cases ,2. The pPatient information: a 2-year-old boy with no known medical illness, initially presented with fever for 8 days, after 2 days he developed bilious vomiting more than 10 episodes per day but still tolerate nourishing fluid, followed by abdomen distension and loose stool 5-10 episodes. Otherwise, none of his family members has any similar symptoms. He has no contact with tuberculosis patients.Clinical findings: his vital signs are normal except fever spike daily. On inspection, he is active and not septic looking. His abdomen is distended but soft and not tender. There is no mass or hernia.Diagnostic assessment: his haemoglobin is 7.6 g/dL, total white blood cell is 8.6 x103/uL, the platelet is 380 x103/uL, normal renal profile and liver function test. His chest radiograph noted right pleural effusion and the abdominal radiograph showed prominent small bowels with thickening walls without a transitional point  with 20 mL frank pus inside the thin cyst wall and adhered to surrounding small bowels. The cyst was severely adhered to and eroded into the ileum (Escherichia coli and Klebsiella pneumoniae which were sensitive to gentamicin, amikacin and cefepime. Histopathological examination reported as a benign omental cyst.he ileum  and caushe ileum  and ileaFollow-up and outcomes: the patient had recovered well after the surgery except for surgical site infection which needed intravenous gentamicin, wound saline flushing and dressing. After a week, the patient´s wound was healed and he discharged home.Patient perspective: the patient was well taken care of during his hospitalization. The parents were relieved with treatment that was carried out on their child. They were happy to see such improvement from day one of admission until the day of discharge.Patient´s consent: informed consent was obtained from the parents for us to utilize the pictures in this manuscript.An intra-abdominal cyst can be grouped by location such as mesenteric, omental, solid organ and retroperitoneum . OmentalDiagnosis can be challenging where omental cyst could present in 3 ways: asymptomatic, chronic abdominal pain and acute abdomen . When omComplete excision is recommended for omental cyst and a laparoscopic approach is recommended . IncomplOmental cyst is rare and usually asymptomatic. Symptomatic omental cyst should be aware and alert of its complications. In complicated omental cyst such as bleeding, intestinal obstruction, infection, torsion, and rupture, urgent surgical intervention is needed. We report here another omental cyst complication which is bowel erosion with perforation. Recommended diagnostic imaging is ultrasound. If in doubt with ultrasound finding, CT and MRI scan is an alternative. Complete excision of omental cyst is gold standard and laparoscope is preferred whenever feasible. If the complete excision is not possible, partial excision followed by marsupialization or OK-432 injection will be an option.


South Africa has included birth companions in its national guidelines for maternity care and the revised Maternity Case Record, in and effort to improve the quality and experience of care. However, reservations amongst healthcare providers remain about the acceptability of birth companions in the labour ward.To document the experiences and perceptions of birth companions who supported women in labour in a rural hospital in Limpopo Province where a Respectful Maternity Care (RMC) project was piloted.An institution-based cross-sectional study design was employed. Purposive sampling was employed where all birth companions who supported a woman during labour and birth were included in the study. The experiences and perceptions of birth companions were captured using a birth companion feedback book during the period of 1st April to 30th August 2019. Thematic analysis was used to analyse the data.Seventy-one (71) of the 73 birth companions only had positive responses about the birthing experience and how both the birth companion and woman in labour were treated. Two birth companions were dissatisfied with the treatment provided by the midwife that supported the birth.It is important for healthcare providers to understand the far reaching emotional and psychological impact of their attitudes and behaviour on, not only women in labour but also on others who witness their  behaviour. Mechanisms to obtain feedback from birth companions should be integrated into strategies to improve the quality and experience of care for women during childbirth. Childbirth is a highly stressful event for many women, which requires the constant involvement of the mind and body, and evoking a wide range of positive and negative emotions , information about labour progress and advice regarding coping techniques, comfort measures  and advocacy  WHO .Despite the overwhelming evidence of the benefits of birth companionship, its implementation is not universal. A study in Brazil found that in spite of the legal obligation to provide a companion to support women during labour, birth companions are still not fully accepted in public hospitals  project was piloted in a sub-district of Limpopo Province, South Africa. One of the key components of the RMC project was for pregnant women to identify a birth companion of choice to support them during pregnancy, labour, birth and postnatal period. The labour ward staff were orientated on the RMC approach and the role of birth companions during the pregnancy, labour and postnatal period. They were also instructed to adjust their infrastructure to accommodate birth companions by ensuring all labour rooms to have a chair and at least a curtain to maintain the privacy of the woman in labour. They were also equipped with information to capacitate birth companions (including pamphlets and posters) and supplied with birth companion toolkits, which comprised items to promote non-pharmacological pain relief, such as birthing balls, hand massages, massage cream, lip balm and so on.A fair amount of resistance was experienced from frontline healthcare workers and managers during the project inception phase. Some of the impediments to successfully implement birth companionship that was identified by frontline healthcare workers and managers during buy-in and orientation workshops included a perceived reluctance of community members to accompany pregnant women into the labour ward and witness the birthing process, inadequate space for birth companions in the labour ward and compromising of client privacy in the presence of birth companions in the labour ward. A review of studies conducted in middle and lower-income countries revealed that in all the studies, healthcare providers displayed negative attitude towards birth companionship, citing the following reasons: fear of cross-infection and overcrowding in labour wards; the complexity of expected collaboration amongst women, their companions and healthcare providers and interference of birth companions with the clinical duties of healthcare providers . The sub-district is constituted by 128 villages and one small industrial town, which makes up a total population of 212 701. The hospital has four First Stage of labour rooms, three Active Stage of labour rooms and one theatre for caesarian sections in the Maternity Ward. The hospital conducts between 400 and 500 births per month. The hospital was selected for the purpose of piloting an RMC project aimed at improving the quality and experience of care for pregnant women during labour and childbirth.An institution-based cross-sectional study design was employed. The experiences and perceptions of birth companions who supported women during labour and childbirth were captured using a birth companion feedback book during the period of 01 April 2019 to 30 August 2019.Birth companions who supported women during labour and childbirth at the district hospital.Purposive sampling was employed where all birth companions who supported a woman during labour and birth were expected to respond and thus included in the study. The midwife supporting each birth was tasked with encouraging each birth companion, who were present during labour and birth to share their experience of supporting a woman during childbirth.Birth companions were encouraged, but not forced, to participate in the study. The purpose of the study was explained to all participants. They were also told that the information obtained from them would be used to improve the quality of care for pregnant women during labour and birth. They were given the option to remain anonymous and were assured that no harm or discriminatory action would befall them or the pregnant woman that they were supporting through participation or non-participation in the study. Birth companions providing feedback in the birth companion book after the purpose of the study was explained to them, was an implication of providing consent to participate in the study.Birth companion is an adult male or female, selected by a pregnant woman, who provides her with continuous physical and emotional support throughout labour and birth.A birth companion feedback book was developed and placed at the nurses’ station for all the birth companions to provide written feedback on their experience and perceptions whilst supporting a woman in labour and childbirth. The book has fields to fill in details such as the name of the woman in labour , the birth companion’s name , the relationship of the birth companion to the woman in labour, date of delivery, name of the midwife who supported the birth and feedback from the birth companion. Healthcare providers were tasked with encouraging the birth companions to document their experiences as soon after the birth as possible and before the woman is transferred from the labour ward to the postnatal ward. The birth companions had the option to record their feedback in their language of choice. The birth companion book was placed on the counter at the nurses’ station in the labour ward. Data from 01 April 2019 to 31 August 2019 were used for the study.Sepedi  were translated into English. Thematic analysis was used to analyse the data. Themes were identified, and then the data were coded and systematically placed in the identified themes. Similarities and contradictions were highlighted.Copies of the data from the Birth Companion Feedback Book were made, as the book could not be removed from the nurses’ station where it was accessible to birth companions. The responses were read by two researchers to make sure that all responses were captured accurately, especially those that were illegible. The responses in Ethical approval was obtained from the University of Limpopoi Turfloop Research Ethics Committee (TREC/59/2019:IR).The district hospital had 1860 births during the study period. Seventy-three (73) birth companions provided written feedback in the Birth Companion Feedback Book during the period between April to August 2019. The low response rate can have multiple interpretations, namely that the majority of mothers during the study period did not have a birth companion to support them during labour and birth (high probability as the concept of birth companionship was new to the community and facility) or not all birth companions documented the birthing experience in the birth companion book . Seventy-one (71) of the 73 birth companions gave only positive responses about the birthing experience and how both the birth companion and woman in labour were treated. Two birth companions were dissatisfied with the treatment of the midwife that supported the delivery. The findings of the study are not generalisable in terms of the proportion of birth companions that had a positive experience versus the proportion of birth companions that had a negative experience during labour and birth. The findings do, however, provide valuable insights into the community acceptability of providing continuous physical and emotional support to women during labour and birth through the use of birth companions.n = 71) of the birth companions were females, and most (58) were a relative of the birthing woman , whilst the rest were volunteer birth companions with no prior relationship with the woman being supported.The majority , helping her to focus on the purpose of labour and its ultimate goal when she feels that she is unable to continue to the end of the birthing process, serving as an intermediary between the woman in labour and the healthcare team by helping the healthcare team to communicate effectively with the woman in labour who may find it difficult to interpret and synthesise information during intense contractions and high levels of anxiety and fear. Birth companions also help to effectively communicate the feelings, needs and desires of the woman in labour to the healthcare team when needed and facilitate non-pharmacological pain relief ‘She was booked for a c-section [caesarian section]. I lay on the floor with her, which is where she preferred to be, and I encouraged and supported her to use different breathing techniques as well as massaging her back and hands and reassuring her. She eventually focused on the breathing and my encouraging messages, which calmed her down and she stopped asking for a c/section. Congratulations to Y on the natural birth of her 2nd baby boy.’ ‘It was a pleasure being a birth companion to Y. She was very anxious and felt that she was not able to handle the pain and she kept begging for a c/section  uniform whereas she [nurse] still has other places to go when she knocks off, unlike the mother. I gave the mother my hand to hold onto as she was being stitched and she almost dug holes into my hand. I felt so sad for the mother … it almost felt like I was the one feeling her pain. It really put a damper on the beautiful experience of the labour and birth.’ ‘The nurse who was helping to deliver the baby was impatient and rude to the mother. Once the baby was delivered and she had to stitch the mother’s vagina where she had cut her, the mother felt a lot of pain and kept moving backwards on the bed. The nurse kept shouting at the mother for moving away and told her that she is going to dirty her [One other birth companion witnessed disrespectful behaviour towards a woman who gave birth on the floor in the passage of the postnatal ward:‘The nurse started screaming at the mother and blaming her for what was happening as if it was her fault that the baby started coming when she was in the passage. Then the nurse started screaming at everyone to go away … I understand she did not want everyone around watching the mother giving birth but she was very rude in how she was speaking to the mother and to everyone in the passage.’ The study aimed to enhance insights into the perceptions and experiences of birth companions of choice, as well as volunteer birth companions, about their role in providing continuous physical and emotional support to women during labour and birth. The study revealed that birth companions generally have positive experiences and perceptions about their role. Their experiences are directly influenced by the attitudes of healthcare workers towards the women that they support during labour and birth.The RMC model that is implemented at the study hospital advocates for all women to be continuously supported by a birth companion during labour and birth. The model also advocates for birth companions to be orientated on their roles and responsibilities as birth companions upon arrival in the labour ward. The orientation appears to have contributed to the positive experience of birth companions, by increasing their sense of confidence and perceived value of their role. Providing physical and emotional support to women in labour is the core purpose and function of birth companions, and thus deriving satisfaction from fulfilling their role is a testament to the need for birth companions during labour and birth.Thus, it is important to invest in equipping birth companions with the necessary knowledge and skills to execute their roles and responsibilities during labour and birth. A competent and confident birth companion not only enhances the experience of labour and birth for the woman being supported but also contributes to the acceptability of birth companions by healthcare providers.Although male partners as birth companions have been associated with reported challenges that include cultural and practical considerations, it does not take away from the important role that they play in family-centred care during labour and birth. The males that participated in the study reported positive experiences of their role in supporting their partners. Far more effort should be made in debunking the myths and misperceptions about male partners as birth companions and normalising their role in supporting women during labour and birth.One other key role of birth companions, which is not always appreciated by healthcare providers, is one of holding healthcare providers accountable. The birth companions are key witnesses to both positive and negative experiences in the labour ward. Their mere presence in the labour ward should, and often does, deter healthcare providers from providing disrespectful and abusive care to women in labour. Accountability is critical for improving the quality of care provided by a health facility, and therefore positive and negative feedback from birth companions should be incorporated into ongoing quality improvement strategies.Although the study provides valuable insights for the integration of birth companions into the labour ward, there are a number of limitations that need to be taken into account. For one, there were no measures to enforce healthcare providers encouraging all birth companions to document their experiences in the birth companion feedback book. The onus was entirely on midwives attending to a birth to do so. Furthermore, it is also possible that some birth companions could have felt intimidated to provide negative feedback in the book, which is placed at the nurse’s station, in spite of the option for them to remain anonymous.The RMC project that was piloted advocates for women to be supported continuously by a birth companion of choice during labour and childbirth. Documenting the experiences and perceptions of birth companions who are supporting women is critical for the continuous improvement of the quality and experience of care by pregnant women during labour and childbirth. It is important for healthcare providers to understand the far reaching emotional and psychological impact of their attitudes and behaviour on not only the women in labour but also on others who witness their  behaviour. Mechanisms to obtain feedback from birth companions should be integrated into the strategies to improve the quality and experience of care for women during labour and childbirth.


Results: Compared to manual GT, IRIS reduced the segmentation time by more than 10-fold. Compared to automated LS, IRIS reduced the mean liver cyst volume error from 42.22% to 13.44% (p < 0.001). IRIS segmentation agreed well with manual GT (79% dice score and 99% intraclass correlation coefficient). Conclusion: IRIS is feasible for fast, accurate liver cyst segmentation in patients with ADPKD.Purpose: To develop and integrate interactive features with automatic methods for accurate liver cyst segmentation in patients with autosomal dominant polycystic kidney and liver disease (ADPKD). Methods: SmartClick and antiSmartClick were developed using iterative region growth guided by spatial and intensity connections and were integrated with automated level set (LS) segmentation and graphical user interface, forming an intelligent rapid interactive segmentation (IRIS) tool. IRIS and LS segmentations of liver cysts on  Most patients with autosomal dominant polycystic kidney disease (ADPKD) develop polycystic liver disease in their later life . Liver c tedious . Automat tedious ,6.The purpose of this study is to develop a rapid semiautomated lesion segmentation tool combining rapid interactive edits with automated segmentation based on computer vision techniques: intelligent rapid interactive segmentation (IRIS). The liver cyst labeling process is intelligently automated while allowing for user interaction to rapidly improve the automated segmentation. We evaluated the speed and accuracy of IRIS for fast liver cyst segmentation in 17 patients with ADPKD.Image data were preprocessed for the liver region of interest (ROI) segmentation preprocessing using a convolutional neural network with residual layers , and imag) at a given iteration by thresholding over an affinity sensitivity relative to its neighboring seed voxel (s) according to their intensity (I) difference, p < 0.5). On the other hand, the antiSmartClick employed the same feature as SmartClick but recursively removed voxels for erasing erroneously included voxels in segmentation such as IRIS provided a graphic user interface for editing the automated LS segmentation with smart features, SmartClick and antiSmartClick, in addition to a simple paintbrush. Similar to the recursive region growing guided by intensity similarity for segmenting the left ventricle in cardiac MRI ,10, Smarsitivity . This rehttps://clinicaltrials.gov/ct2/show/NCT00792155, accessed on 31 January 2022), an ongoing longitudinal investigation of ADPKD conducted at our medical center [n = 5) and 3 T (n = 12) MRI systems  between 1 January 2017 and 31 July 2021. Cases were selected randomly from ADPKD-positive subjects, and selection was based on the presence of MRI data were obtained from patients enrolled in the Polycystic Kidney Disease Repository , as well as the automated level set (LS). Segmentation times were recorded for all methods. The similarity between the segmented cyst spatial distributions by the two methods was evaluated using the dice score to assess geometric match and intraclass correlation coefficient (ICC) to assess volume agreement. The liver cyst signal-to-noise ratio (SNR) was measured as the cyst signal intensity ROI mean over standard deviation; the liver cyst–liver contrast-to-noise ratio (CNR) was measured as the cyst to adjacent liver signal difference over the cyst signal ROI standard deviation; and the cyst SNR and CNR measurements were performed over three representative cysts per patient. The 1.5 T cases were compared with 3 T cases with matching cyst patterns. The liver cyst volumes measured on all segmentations were compared using linear regression and the Bland–Altman plot. The statistical significance between LS and IRIS was assessed using Student’s p = 0.05), the cyst CNR was 3.26 ± 0.95 vs. 2.64 ± 0.81 (p = 0.25), the manual processing time was 2072 ± 1383 vs. 2369 ± 925 (p = 0.64), and the IRIS processing time was 179 ± 72 vs. 236 m ± 82 (p = 0.26). There was no significant difference in processing time between 1.5 T and 3 T; for further analysis, all cases were aggregated together and the cyst SNR/CNR on average over all cases was 35.77/3.08.For 3 T vs 1.5 T matched comparison, the cyst SNR was 42.45 ± 25.20 vs. 19.74 ± 14.40 (p = 8.92 × 10−6).Speed metrics comparing GT, LS, and IRIS are shown in p = 5.53× 10−4), decreased the mean ± STD liver cyst volume  from 42.22 ± 44.49% to 13.44 ± 9.70% (p = 0.0097), increased ICC from 98.91% to 99.54%, and decreased the liver cyst volume root mean squared error (RMSE) from 66.4 mL to 35.9 mL  from 0.922/0.976  segmentation, significantly improving cyst segmentation accuracy as measured by dice score and liver cyst volume differences. IRIS reduces the liver cyst segmentation time by more than 10-fold compared to manual segmentation, down to 3.4 min on average, making segmentation of numerous cysts in ADPKD liver clinically feasible.The large number and heterogeneity of liver cysts in ADPKD patients have made automated segmentation of these cysts challenging ,6. A majThe level set method selected for automated cyst segmentation in this study is a popular approach that starts with the user’s initial segmentation and evolves into the desired segmentation . It is kIt should be noted that manual segmentation is not a perfect ground truth. Small cysts can be missed on manual segmentation because it is so tedious and tiring, as exemplified in This encouraging preliminary study has identified several limitations for future improvements. (1) Both manual and level set segmentation have difficulties in segmenting small cysts due to poor conspicuities, which remains a challenge for IRIS. Though the current clinical management is based on total liver cyst volume, small cyst identification may allow the study of their progression. A cause of poor conspicuity is motion artifacts, which should be minimized as required so in clinical practice. Another case of poor conspicuity is noise, which should be further investigated. (2) Vascular structures also appear hyperintense on ensation ,22,23,24ensation ,25. (4) In summary, intelligent rapid interactive segmentation (IRIS) is feasible for fast and accurate liver cyst segmentation in autosomal dominant polycystic kidney disease (ADPKD), using SmartClick and antiSmartClick to rapidly refine automated level set segmentation. The accuracy performance of IRIS segmentation closely matches that of the manual segmentation.


Home birth is experienced by people very differently worldwide. These experiences likely differ by the type of stakeholder involved , the experience itself , and by the health system within which home birth occurs . Research evidence of stakeholders’ perspectives of home birth could usefully inform personal and policy decisions about choosing and providing home birth, but the current literature is fragmented and its breadth is not fully understood.We conducted a systematic scoping review to understand how the research literature on stakeholders’ perspectives of home birth is characterized in terms of populations, settings and identified issues, and what potential gaps exist in the research evidence. A range of electronic, web-based and key informant sources of evidence were searched. Located references were assessed, data extracted, and descriptively analyzed using robust methods.Our analysis included 460 full reports. Findings from 210 reports of studies in high-resource countries suggested that research with fathers and same-sex partners, midwives, and vulnerable populations and perspectives of freebirth and transfer to hospital could be synthesized. Gaps in primary research exist with respect to family members, policy makers, and those living in rural and remote locations. A further 250 reports of studies in low- and middle-resource countries suggested evidence for syntheses related to fathers and other family members, policy makers, and other health care providers and examination of issues related to emergency transfer to hospital, rural and remote home birth, and those who birth out of hospital, often at home, despite receiving antenatal care intended to increase healthcare-seeking behavior. Gaps in primary research suggest an examination is needed of perspectives in countries with higher maternal mortality and among first-time mothers and young mothers.Our scoping review identified a considerable body of research evidence on stakeholder perspectives of home birth. These could inform the complex factors influencing personal decisions and health system planning around home birth in both high- and low- and middle-resource countries. Future primary research is warranted on specific stakeholders worldwide and with vulnerable populations in areas of high maternal mortality. Childbirth is an important event for a woman and her family –3. BirthBetween 1 and 16% of childbearing people in high-resource countries (HRCs) choose to give birth at home, where midwifery services are well-integrated into the health system model of care –12. HereWithin this myriad of personal, societal, and health system influences, women decide whether to birth at home, their partners decide whether and how to support them, and practitioners and policy makers plan, deliver, and evaluate home birth services. Evidence from research examining the experiences of key stakeholders, including women, partners, family members, health care practitioners, policy and decision-makers, could usefully inform personal and policy decisions regarding home birth. Different stakeholders’ perspectives can provide an important source of evidence underpinning quality of care in both hospital facilities and planned home births . ListeniA large amount of qualitative research on women’s experiences of home birth exists and may be useful, however, this evidence comes from diverse populations. Several previous systematic reviews have examined the perspectives of women, midwives and nurses. The majority of these focus on women’s views in high-resource countries –39. Of tThe primary research exploring perspectives other than women or practitioners is disparate and may provide conflicting findings in countries where home birth is, and is not, well integrated –49. ThesTo facilitate evidence-informed decision-making among women, their support persons, health care professionals, and those setting clinical and policy standards, there is a need to understand the body of research examining the experiences and perspectives of home birth as voiced by those who are involved in home birth decisions. This involves first understanding the breadth of evidence that has been conducted and the types of participants, settings and contexts in which home birth research has been conducted.By mapping or scoping the breadth of research on people’s perspectives of home birth, our aim is to understand the range of debates on the value and place of home birth in different communities and among different populations. By mapping or scoping the breadth of research on people’s perspectives of home birth, our aim is to understand the range of debates on the value and place of home birth in different communities and among different populations. Collating this research literature will identify the breadth of research on this topic, examining determinants such as ethnicity, socioeconomic status, disability, sexual/gender orientation, migration status, age, geography, and with health system factors which interact with issues of sex or gender and influence birth processes and outcomes , 61. SucHow is the research literature on stakeholder perspectives, opinions, and views of planned home birth characterized in terms of populations, settings, and identified issues?Where are there gaps in the research evidence on stakeholder perspectives of planned home birth?In order to prioritize the populations and topics where home birth research exists and could be synthesized usefully for evidence-informed policy, practice and personal decisions, the research landscape must be understood . A scopiA review protocol was published on the McMaster Midwifery Research Centre’s website in March 2020 .As part of a larger CIHR-funded knowledge planning and dissemination grant (CIHR #162186), we consulted an advisory group comprised of midwifery researchers, obstetric, family practice and midwifery practitioners, and a member of the public with maternity policy expertise. Advisory group members were consulted twice: first to advise on review methods and identify potentially relevant key research and second to consider and interpret emerging findings.Searches were updated from our previous systematic review of home birth , 16 and Were an empirical study ;Concerned women/clients who planned to or did give birth at home;Aimed to elicit views, perspectives, opinions or experiences of any stakeholders ;Were published in English or are translatable; andWere published from 2010 onward.All identified references were screened hierarchically and included in the review if they:We excluded narrative descriptive birth stories that described events or outcomes, but any research including rationales, reasons, motivation, values, perspectives, and decision-making as part of the descriptive were included. As English language is the research team’s primary language, this was the minimum required for adequate eligibility screening. However, studies in other languages were marked for possible future research. To ensure that the included research reflected current professional guidance and stakeholder perspectives on home birth, a date limit of 2010 was used. This reflected either the date since data were collected or when the reference was published. Studies were also excluded that focused solely on hospital birth or alternative birth center settings.Data from included studies were extracted using previously developed modified coding frameworks that were informed by the advisory group , 65. ExtTo establish the breadth of research conducted on home birth, extracted study characteristics were descriptively analyzed and summarized in tabular format. Descriptive frequencies of all study characteristics  were calculated using Excel. Assessing risk of bias or critical appraisal of studies was not undertaken, as this stage is not appropriate for a scoping review where the aims are to understand the nature and breadth of research in an area of inquiry , 67. SimEPPI-Reviewer software was utilized for review processes. The protocol and final report were developed as per PRISMA(-P) reporting guidelines , 71. ForAs a scoping review, registration was not possible in PROSPERO’s systematic review register. Instead, the protocol was made publicly available on McMaster University’s Midwifery Research Centre website . Two altn = 3353), were not focused on home birth (n = 2770), or were not research on people’s perspectives (n = 1728). The flow of studies through the review is provided in Fig. Searching identified 10,196 references. After duplicate removal and screening on title and abstract, a total of 720 references were retrieved for assessment based on the full report. Of these, 460 met the eligibility criteria and were included in the scoping review analysis. Most studies were excluded at title/abstract or full text screening stages because they were not empirical research , followed by Australia (20%), the USA (16%), the Netherlands (11%), and Canada (9%). It should be noted that some studies sampled from more than one country, hence numbers add up to the overall totals for HRCs reported above. Several HRCs were not represented, including Chile and Colombia, South Korea, and several countries within Europe .The experiences of a wide range of clients, support persons, and health care practitioners were sought across high-resource countries, as illustrated in Fig. n = 3) and policy makers (n = 2) regarding home birth were rarely studied.Women’s experiences were most often reported , although the perspectives of fathers (9%) and family members (2%) were also included in some studies. Midwives were the most frequently researched healthcare providers (32%), followed by obstetricians (11%), nurses (5%) and family practitioners (4%). Pediatricians (1%) and other health care providers  were studied less often (3%). The views of service managers (4%) and staff members (2%) were studied infrequently. The perspectives of community leaders . Another 67 studies (32%) focused on understanding home birth from the perspectives of those providing home birth services.The perspectives of different types of clients were also the main focus of a group of studies. Perspectives of home birth among women experiencing their first pregnancy were reported in 23 studies within HRCs (11%), with only 5% asking multiparous women. The experiences of rural and remote participants (3%), Indigenous groups (3%), and immigrants (one study) were less often reported.Some studies also explored purposely the views of partners and family members: the perspectives of fathers or partners were the specific focus in nine studies (4%). Only one study sought the experiences of children/siblings who were present during home births.Perspectives on risk in home birth were also a focus. A total of 11 studies (5%) considered the experiences of those who chose to freebirth. The experiences of home birth for those with high-risk pregnancy were reported in eleven studies (5%) and of women who had a previous hospital delivery in eight studies (4%). The perspectives of those who experienced transfer from home to hospital during birth were reported in 15 of the included HRC studies (7%).A slightly higher proportion of the included studies took place in low- and middle-resource countries (LMRCs): a total of 250 studies eliciting the views of stakeholders about home birth across 48 countries. This is shown in Fig. Studies of stakeholder perspectives of home birth were conducted in multiple LMRCs, as illustrated in Fig. The largest body of research in this group has been conducted in Ethiopia . A modest number of studies have been conducted in other countries with high rates of maternal mortality including Brazil (9%), Nigeria (7%), India (6%), Tanzania and Kenya (5%), and Zambia, Nepal, Ghana, and Bangladesh (4% each). Countries with the highest maternal mortality rates  as defined by the WHO, UNICEF, the UN Population Fund, and the World Bank  were parAs in studies conducted in HRCs, the perspectives of women experiencing home birth in LMRCs were most often sought . This is shown in Fig. Many other types of stakeholders participated in home birth research studies across LMRCs. Fathers perspectives were explored in 45 studies (18%), as were family members (8%). A diversity of healthcare providers perspectives were also studied, including outreach workers, health extension workers, and unspecified health workers (17%). The experiences of traditional birth attendants were reported in similar proportions (17%), followed by midwives (8%), nurses (7%), and skilled birth attendants (2%). The experiences of service managers (5%) and staff members and obstetricians (2% each), family practitioners (three studies), and pediatricians (one study) were less often reported.A modest number of studies within LMRCs included the perspectives or community leaders (10%), followed by community members (9%), and policy makers (4%). Perspectives of academics or social service personnel (two studies each) and religious leaders (one study) were less often stated.A wide range of topics were studied across LMRCs, as shown in Fig. Within LMRCs, participants’ perspectives shaped by geographic and economic determinants were evidenced, with studies of those experiencing rural or remote home birth , in poorly resourced areas (20%), nomadic or pastoralist communities (5%) studied.Almost one third of the studies in LMRCs sought to understand home birth from the perspective of those people experiencing home birth . The focus of those providing home birth services was examined in 32 studies (9%).Many of the studies conducted in LMRCs sought to understand why home birth took place despite an emphasis on promoting health facility delivery (26%). Other related studies examined perspectives of women who experienced home birth despite receiving antenatal care (6%), or not utilizing antenatal care (2%). The views of those women experiencing previous hospital delivery were reported in four studies (2%). Another six studies (2%) examined the views of those experiencing transfer from home to hospital.Specific populations at risk of poor outcomes were less often studied, including first time mothers, multiparas, and Indigenous groups (four studies each), refugees and migrants, and those with high-risk pregnancies (three studies each). Studies originating in LMRCs with a specific focus on the perspectives of fathers only were rarely reported (one study).It has long been considered important that health policy and practice decisions should be informed by the perspectives of those who plan, provide and are affected by them . The resIn HRCs, a body of research was located on fathers’ and same-sex partners’ experiences of home birth. A synthesis of the existing literature on these partners’ perspectives of home birth in high resource countries is an important area of need, as this appears to be a new area of birth research. In LMRCs, it has been suggested that fathers and other family members influence women’s health care decisions, including place of birth –82. Our A substantial number of studies examining LMRC community members’ views of home birth were also located. This could further supplement existing evidence syntheses of community interventions to prevent maternal and newborn mortality , 86. In Health professionals’ perspectives of home birth also hold the potential to inform maternity policy and practice; however, only one previous systematic review was located which examined midwives’ discussions of place of birth options with women in HRCs . This scSeveral topics or issues of interest also emerged from the analysis of HRC research on stakeholder views of home birth. This included new primary research on people’s perspectives of freebirth or unassisted birth, where women choose to birth without a trained professional present, even where there is access to medical facilities. Previous syntheses of this research suggest that women make this choice, for reasons of autonomy, choice, and control over their own bodies, due to midwives and current maternity services , 87. ThiSimilarly, our scoping review identified multiple research studies of stakeholder perspectives on home birth in high-risk pregnancy, in those who had a previous hospital delivery and among women experiencing transfer from home to hospital. Integration of this body of research conducted in high-resource settings could broaden our understanding of home birth with reference to safety and risk. For example, this could update an existing evidence synthesis examining perspectives of transfer from home to hospital . This foSeveral studies originating in LMRCs also examined stakeholder perspectives of home birth where the population is rural, remote, or has poor access to health services. It has been noted that poor geographic access to hospital facilities in LMRCs impedes health care utilization . StakehoThis scoping review of stakeholder research about home birth also identified several gaps in primary research. For example, in high-resource countries, very little research was identified which sought the views of same-sex childbearing partners, or other family members, such as grandparents. Given the influence of family members on women’s birth decisions , 81, 82,The views of specific populations concerning home birth also bear further examination. These include the perspectives of stakeholders in countries of higher maternal mortality, including countries in sub-Saharan Africa and Southeast Asia .Research on the perspectives of first-time mothers and multiparas, whose experiences may differ from one another, could also suggest different avenues of health system support.In addition, primary research seeking young mothers’ perspectives of home birth was rarely located. Given that the highest rate of maternal mortality in LMRCs occurs in women aged 10 to 14 years, this is an important area of future research .Finally, primary stakeholder research on home birth among specific and potentially more vulnerable populations is also lacking in both HRCs and LMRCs, including Indigenous populations, immigrants, refugees, and migrants. Displaced populations are at higher risk of maternal mortality due to the associated conflict and humanitarian crises . This suThe main strength of this systematic scoping review lies in its broad search for relevant literature and consistent methods of screening, coding and analysis. To our knowledge, this is the first representation of the landscape of qualitative literature worldwide focused specifically on stakeholders’ experience and perspectives of home birth. As such, it provides a valuable resource for researchers, members of the public and decision-makers for informing personal and policy decisions related to home birth and identifies areas for future research.The results of this review are limited by the depth of analysis possible using scoping review methods, a challenge noted by others , 96. TheOur systematic scoping review identified a large body of research literature that privileged the experiences and perspectives of a wide range of key stakeholders about home birth in both high and low and middle income countries.Groups of primary research focused on different topics and populations within HRCs and LMRCs could be usefully synthesized to inform personal practice and policy decisions. However, these research syntheses would be best informed by collaboration between researchers and childbearing women and their support people, clinicians, professional organizations, research funders, and clinical and policy decision-makers. These stakeholders can better inform personal and policy decisions by working together to collectively identify emerging issues, priorities, and the associated research questions , 97, 98.


The underlying pathogenesis of cerebral palsy (CP) remains poorly understood. The possibility of an early inflammatory response after acute insult is of increasing interest. Patterns of inflammatory and related biomarkers are emerging as potential early diagnostic markers for understanding the etiologic diversity of CP. Their presence has been investigated in plasma and umbilical cord blood but not in cerebrospinal fluid (CSF).A clinical CP sample was recruited using a single-time point cross-sectional design to collect CSF at point-of-care during a standard-of-care surgical procedure . Patient demographic and clinical characteristics were sourced from medical chart audit.p ≤ 0.001) associations were found among neuroinflammatory, neuroendocrine, and nociceptive analytes with association patterns varying by birth status . When between birth-group correlations were compared directly, there was a significant difference between preterm and extremely preterm birth subgroups for the correlation between tumour necrosis factor alpha (TNFα) and substance P.Significant (This investigation shows that CSF can be used to study proteins in CP patients. Differences in inter-correlational patterns among analytes varying by birth status underscores the importance of considering birth status in relation to possible mechanistic differences as indicated by biomarker signatures. Future work should be oriented toward prognostic and predictive validity to continue to parse the heterogeneity of CP’s presentation, pathophysiology, and response to treatment.The online version contains supplementary material available at 10.1186/s12883-021-02333-2. Cerebral palsy (CP) is a neurodevelopmental disorder of movement, muscle tone or posture caused by an insult to the developing brain before birth, at birth, or before the age of two years. CP is the most common motor disability in childhood, affecting an estimated 500,000 American children and occurring in approximately 2 children per 1,000 live births. The pathogenesis of CP is not fully understood. CP risk factors predominantly involve perinatal factors such as anoxia and ischemia and prenatal factors such as young gestational age, intrauterine viral infections, and maternal thyroid abnormalities. Intrauterine infection and inflammation are of particular interest with both maternal response (chorioamnionitis) and fetal response  being associated with white matter damage (WMD) and CP ; Adjusted P (Adj P) = 0.041)  Fig. .Fig. 2ViPreterm Birth status resulted in clusters of analytes that were highly correlated to one another Fig. . There wExtremely Preterm Birth status also resulted in distinct analyte correlations different from both Term Birth and Preterm Birth participants Fig. . There wp < 0.05).Differences in correlations between subgroups were also directly tested. As noted above, to be included in between-group analysis, each correlation first had to be statistically significant within the subgroups. Thirty-two pairs of correlations were statistically significant across all subgroups. Then the identified correlations were tested against one another to check whether they were significantly different by birth status. Based on this approach, there was a significant difference between the Preterm and Extremely Preterm Birth subgroups for the correlation between TNFα and substance P . Of the many putative causal agents and pathways to CP, the role of neuroinflammation in perinatal brain damage has received considerable empirical attention. There has also been considerable conceptual emphasis challenging conventional wisdom about the nature of the threat in relation to inflammation and the developing brain with a distinct shift to a perspective that a core underlying feature may be less about static events  and more about sustained states . The significance of this shift is in widening the focus of inquiry to include tertiary mechanisms of brain damage, which, in turn, could shed new light on a very old problem – namely treating CP based on its underlying pathophysiology.working hypothesis that suggests that the relationship among key neuroendocrine hormones, excitatory neuropeptides, and neuroinflammatory cytokines as markers may be a critical variable predicting outcome. The conceptual basis for this is the past two decades of work supporting the cross-talk among the endocrine, nociceptive, and immune systems. In healthy states there is an optimal balance between stress hormones and proinflammatory cytokines. In children with CP, the white matter damage may be ‘driving’ an immune-mediated inflammatory cascade. There is evidence supporting this possibility from three related studies with CP patients, one using umbilical cord serum [There is a rd serum , one usird serum , and onerd serum .The current analysis expands the previous work and provides further description of the molecular milieu present in the CNS of CP patients. Such documentation provides a unique opportunity to consider how differences in CNS concentrations of various inflammatory-relevant analytes between differing presentations of CP may be relevant for hypotheses about mechanisms underlying the differential outcomes in CP. Specifically, in this sample, it was observed that Term Birth, Preterm Birth, and Extremely Preterm Birth status was associated with distinct patterns of analyte inter-correlations. If reproducibility of these findings could be established, there is an opportunity to better understand the mechanisms underlying various and varying outcomes specific to birth term in CP.The correlations present in the participants suggest relationships among systems subserving arousal (orexin A), inflammation (TNFα), anti-inflammation (IL-1ra), and neuronal excitation (substance P), with distinctions depending on birth term. Orexin A (hypocretin 1) is an excitatory, hypothalamic neuropeptide that binds to both the orexin 1 and 2 receptors (OX1R and OX2R); the former is thought to act largely through the excitatory Gq protein and both are implicated in wakefulness and sleep cycle stability . NarcoleIn clinical investigations, evidence suggests an autoimmune destruction of orexin neurons , and ore2 [Further, the relevance of the difference between the Preterm and Extremely Preterm subgroups appears particularly striking and significant given the literature documenting the clinical differences in phenotypic presentation between these two groups. Understanding the relationship between TNFα and substance P expression and regulation may have implications related to the underlying pathophysiology with possible prognostic and treatment relevance. One study of cultured human astrocytes demonstrated a functional interaction between these two analytes: substance P enhanced the stimulatory effect of TNFα on production of two inflammatory mediators: IL-6 and PGE2 . This biFrom a knowledge translation perspective, the correlation difference between Preterm and Extremely Preterm Birth subgroups for TNFα and substance P may represent a potential interaction and intervention point between inflammation and nociceptive neurotransmission specifically in the CNS; however, demonstration of a spinal or trigeminal localization of this interaction would be required to underpin this interpretation. Such an understanding may provide an opportunity to improve outcomes through earlier intervention that includes targeting these specific pathways and their unique mechanisms. One weakness of the current analysis is that the group sizes are not robust enough to distinguish larger signature patterns/differences between groups that may be informational for identifying distinctions between different patient subgroup populations; ultimately, there may be different CP patient subgroups with specific, identifiable protein signatures. Larger samples with confirmatory analyses are needed. Additionally, further consideration regarding appropriate comparison groups or control samples is warranted. Healthy controls could be useful  but their use could be limited in so much as it might be more important to consider inclusion of carefully defined samples from other neurodegenerative disorders in which more is known about the underlying immune pathology and disease progression . Doing so would provide important points of comparison for similarities and differences in inflammatory analyte levels/profiles that would, in turn, increase our understanding of inflammatory mechanisms specific to the CP phenotype.Our long-term goal is to establish clinical value in adopting a biomarker approach to understand clinical outcomes among patients with CP. A biological marker or biomarker is any characteristic that can be measured and evaluated as an indicator of normal biologic processes, pathologic processes, or pharmacologic responses to therapeutic intervention. Biomarkers hold the potential of a better understanding of the etiology and pathology of a given disorder, providing valuable insight into diagnosis, treatment, and prognosis for many debilitating disorders and diseases. Current diagnostic and therapeutic approaches to manage chronic disability among individuals with neurodevelopmental disorders including CP are limited by our narrow understanding of the biological mechanisms underlying developmental disorders of various etiologies and confounded further by phenotypic and etiologic heterogeneity  and the lack of biomarkers predictive of therapeutic outcome.Part of the hope is that molecular biomarkers may provide a useful ‘work around’ for closing the gap between clinical presentation and often unknown underlying pathophysiology in CP. To get there, however, there are enormous gaps in what is known from a normative perspective within the population of CP . The difficulty with any clinical sample is whether the detectable analyte represents a biomarker for ‘exposure’ (to an inflammatory process) or ‘outcome’ (of brain damage). There is no easy solution to this dilemma absent an experimental model. With that point acknowledged, we believe there is value in continuing to adopt and adapt a ‘biomarker epidemiological’ perspective as outlined by Dammann . Doing sIn particular, it would be important to obtain comparison values from healthy and/or non-inflammatory based controls to establish the utility of neurochemical profile patterns as prognostic  or predictive tools . With that said, as noted above, careful selection of other well-defined diseases in which immune-mediated inflammation is a core feature would also be a valuable approach . A thirfunctional consequences of altered inflammatory processes and responses in children with CP and to consider the potential for mechanism-driven intervention based on protein/peptide/neurotransmitter signatures in CP patients. Increasing our scientific understanding of the neurochemical milieu involved in distinct subgroups of CP may shed light on potential targets for earlier intervention to perhaps prevent transition to more severe presentation. Clarifying a mechanistic understanding of developmental differences may be what the analyte patterns are pointing to and offer a specific starting domain for further exploration. Our hope is that these preliminary findings lay the groundwork for additional studies to confirm and expand on the potential for protein signatures in CP to be valuable clinical tools in the future.Given the preliminary data presented here: 1) that endocrine, neuropeptide, and inflammatory markers are detectable in CSF from pediatric patients with CP and 2) that significant correlations exist among markers for endocrine hormones, nociceptive neuropeptides and inflammatory mediators that are distinct in various subgroups of individuals with CP, we think it is critical to continue this line of research to consider further the Additional file 1: Table 1. A Pearson’s correlation test against the null hypothesis of 0 was conducted for all possible pairs of analytes assayed, controlling for familywise Type I errors using the Benjamini & Hochberg (1995) false discovery rate correction. As there were 528 correlation tests, only those retaining a significant correlation (p ≤ 0.05) after the false discovery rate correction are presented. Table 2. Pearson’s correlation coefficients between pairs of analytes within the Term Birth gestational age subgroup. Only significant correlations (p ≤ 0.05) after controlling for false discovery rate are presented. There were no unique analyte correlations specific to those with Term Birth that were not also significant within the other gestational age subgroups. Table 3. Pearson’s correlation coefficients between pairs of anlytes within the Preterm Birth gestational age subgroup. Only significant correlations (p ≤ 0.05) after controlling for false discovery rate are presented. Table 4. Pearson’s correlation coefficients between pairs of analytes within the Extremely Preterm Birth gestational age subgroup. Only significant correlations (p ≤ 0.05) after controlling for false discovery rate are presented. Figure 1. Visual representation of the direction and strength of the Pearson’s correlation coefficients between analytes assayed within the subgroup with spastic CP. Positive (blue), negative (red), strong (dark shading), and weak (light shading) correlations are depicted. Table 5A. Pearson’s correlation coefficients between pairs of analytes within the subgroup with spastic CP. Complete dataset of significant correlations (p ≤ 0.05) after controlling for false discovery rate are presented. Table 5B. Significant Pearson’s correlations (p ≤ 0.001) between analyte pairs in the subgroup with spastic CP. There were 8 unique positive analyte correlations (bold font) specific to spastic CP that were not significant within the subgroup with mixed tone CP. Figure 2. Visual representation of the direction and strength of the Pearson’s correlation coefficients between analytes assayed within the subgroup with mixed tone CP. Positive (blue), negative (red), strong (dark shading), and weak (light shading) correlations are depicted. Table 6A. Pearson’s correlation coefficients between pairs of analytes within the subgroup with mixed tone CP. Complete dataset of significant correlations (p ≤ 0.05) after controlling for false discovery rate are presented. Table 6B. Significant Pearson’s correlations (p ≤ 0.001) between analyte pairs in the subgroup with mixed tone CP. There were 7 unique positive analyte correlations (bold font) specific to mixed tone CP that were not significant within the subgroup with spastic CP. Figure 3. Visual representation of the direction and strength of the Pearson’s correlation coefficients between analytes assayed within the subgroup with seizures present. Positive (blue), negative (red), strong (dark shading), and weak (light shading) correlations are depicted. Table 7A. Pearson’s correlation coefficients between pairs of analytes within the subgroup with seizures present. Complete dataset of significant correlations (p ≤ 0.05) after controlling for false discovery rate are presented. Table 7B. Significant Pearson’s correlations (p ≤ 0.001) between analyte pairs in the subgroup with seizures. There were no unique analyte correlations specific to those with seizures that were not also significant within the subgroup without seizures. Figure 4. Visual representation of the direction and strength of the Pearson’s correlation coefficients between analytes assayed within the subgroup without seizures. Positive (blue), negative (red), strong (dark shading), and weak (light shading) correlations are depicted. Table 8A. Pearson’s correlation coefficients between pairs of analytes within the subgroup without seizures. Complete dataset of significant correlations (p ≤ 0.05) after controlling for false discovery rate are presented. Table 8B. Significant Pearson’s correlations (p ≤ 0.001) between analyte pairs in the subgroup without seizures. There were 30 unique positive analyte correlations (bold font) specific to those without seizures that were not significant within the subgroup with seizures. Figure 5. Visual representation of the direction and strength of the Pearson’s correlation coefficients between analytes assayed within the subgroup with quadriplegia. Positive (blue), negative (red), strong (dark shading), and weak (light shading) correlations are depicted. Table 9A. Pearson’s correlation coefficients between pairs of analytes within the subgroup with quadriplegia. Complete dataset of significant correlations (p ≤ 0.05) after controlling for false discovery rate are presented. Table 9B. Significant Pearson’s correlations (p ≤ 0.001) between analyte pairs in the subgroup with quadriplegia. There were 16 unique positive analyte correlations (bold font) specific to those with quadriplegia that were not significant within the subgroup without quadriplegia. Figure 6. Visual representation of the direction and strength of the Pearson’s correlation coefficients between analytes assayed within the subgroup without quadriplegia. Positive (blue), negative (red), strong (dark shading), and weak (light shading) correlations are depicted. Table 10A. Pearson’s correlation coefficients between pairs of analytes within the subgroup without quadriplegia. Complete dataset of significant correlations (p ≤ 0.05) after controlling for false discovery rate are presented. Table 10B. Significant Pearson’s correlations (p ≤ 0.001) between analyte pairs in the subgroup without quadriplegia. There were 2 unique positive analyte correlations (bold font) specific to those without quadriplegia that were not significant within the subgroup with quadriplegia.


Therapy choices for cystic echinococcisis (CE) are stage-specific: surgical, minimally invasive, medical or observation without intervention. PAIR  has been considered the treatment of choice for uncomplicated echinococcal liver cysts. However, PAIR carries the risk of toxic cholangitis or hypernatremia and that the cyst frequently refills with bile after withdrawing the catheter. We treated a patient with a giant CE 1 liver cyst with puncture drainage (PD) under albendazole coverage. Drainage enabled us to monitor the morphology of protoscolices under praziquantel (PZQ) co-medication. Protoscolices degenerated within 5 days of PZQ 50 mg/kg/d. The cyst cavity solidified with no evidence of reactivation or secondary spread. Percutaneous treatments can replace surgery in a significant number or cases with hepatic CE. PD allows to assess microscopically the viability of protoscolices under co-medication with PZQ–albendazole and to avoid the instillation of topical scolicides. The clinical management of cystic echinococcosis (CE) is complex, as the various manifestations of this disease with multiple variables such as cyst number, dimension, stage, anatomical location make a systematic analysis difficult. An expert group convened by the World Health Organization has proposed a more rational approach to CE through a standardized ultrasound classification of echinococcal cysts , 2. HepaEchinococcus granulosus EIA IgG 92 AU ; HAT IgG 1: 1024 . Secondary extrahepatic dissociation of CE was excluded by abdominal CT and imaging of the lungs and brain.A 30-year-old Kurdish patient from Syria visited the Institute for Tropical Medicine in Berlin because of suspected CE of the liver. Ten days earlier, a cholecystectomy had been performed because of acute gallbladder hydrops due to the compression of the cystic duct by a large liver cyst. The surgeons decided against removal of the large cyst during the emergency surgery. When the patient visited our outpatient department, the imaging showed a typical CE1 liver cyst with a characteristic external echogenic wall and a size of 15.5 × 9.2 × 8.1 cm  therapy was started with a standard dose of 2 × 400 mg/day. After carefully examining all treatment options, we decided on a minimally invasive approach: a lockable 12-F drainage catheter  was percutaneously inserted into the liver cyst using a Seldinger approach inserted into the liver cyst and fixed to the skin with a suture Fig. . The ABZAnother 4 months later, the cyst cavity had narrowed to 5.0 cm and solidified into a CE4 cyst until last seen 23 months later. Thus, the ABZ therapy was ended. During the 23-month monitoring period to date, there has been no evidence of a relapse or occurrence of secondary CE .Larger uncomplicated CE1 and CE3a cysts can be treated with percutaneous treatments depending on their size , 4, 9. Padictory –22. TherCystic echinococcosis (CE) is a worldwide widespread zoonosis that has been included by the WHO into the list of Neglected Tropical Diseases (NTD). In this context, CE is classified as an "orphan disease" . CE mainIn non-endemic areas, CE mainly affects refugees and immigrants from rural areas, where the prevalence of CE can exceed 5% . In termConcluding, CE is a global zoonosis that requires a complex, stage-appropriate, multidisciplinary therapeutic approach. Optimal treatment of hepatic echinococcosis depends on the WHO staging through imaging Fig. . Surgica