N = 129), born < 37 weeks gestational age, between 1 January and 31 December 2015. Two binary logistic regression models  were constructed to identify predictors of preterm neonatal mortality. Roughly 12% of the infants died after being admitted to the NICU. The binary logistic regression (infant model) had an excellent fit (area under the curve (AUC): 0.904, misclassification rate: 11.7%) whilst the maternal binary logistic model had a fair fit (AUC: 0.698). Birth weight, length of time on the ventilator and obstetric complications proved to significantly influence the odds of preterm neonatal death. The estimated models show that improvement in neonatal as well as maternal variables has direct impact on preterm neonatal mortality.Preterm neonatal mortality contributes significantly to the high incidence of death among children under five years of age. Neonatal mortality also serves as an indicator of maternal health in society. The aim of the study is to examine the risk factors for preterm neonatal mortality at the neonatal intensive care unit (NICU) at Mount Hope Women’s Hospital in Trinidad and Tobago (MHWH). In this retrospective study, we included infants ( Preterm birth is a significant factor in mortality among children who are under five years, as well as the leading cause of neonatal mortality due to the complications associated with preterm births . PretermBlencowe et al. reported that not only is preterm birth a major cause of mortality, but also a major contributor to loss of human potential due to neonatal morbidities . There iPreterm birth can be classified based on gestational age as extremely preterm (less than 28 weeks), very preterm (between 28 and 32 weeks), moderate (between 32 and 34 weeks), and late preterm (34 to less than 37 weeks) . PretermThere have been a number of previous studies attempting to identify the risk factors associated with preterm birth in different countries. In a study conducted by Stoll et al. the rate of survival to discharge was directly proportional to gestational age . SimilarBin Pak and Horiuchi found no significant relationships between maternal factors  and preterm birth . HoweverA comparison analysis of child and infant mortality, including Latin America and the Caribbean, revealed that Trinidad and Tobago is falling behind its regional counterparts, even though these countries have smaller per capita incomes and lower per capita health . Table 1In Trinidad and Tobago, routine data on preterm births are usually not collected and if so, are rarely reported. This analysis will help in understanding the factors that are related to preterm neonatal mortality. Considering the high preterm rate as well as the relatively higher mortality, there is an urgent need to conduct a research that would guide medical practitioners, care-givers, policy-makers and the Government in drawing effective plans and in making informed decisions with regard to preterm neonatal morbidity and mortality.This study examined the neonates delivered at gestational age less than 37 weeks and admitted to Mount Hope Women’s Hospital in Trinidad and Tobago (MHWH) neonatal intensive care unit (NICU) for the period 1 January–31 December 2015. All medical variables were identified by their standard accepted and practiced usage. It must be noted that the data collection was manual in nature and not all the variables from other studies in the literature were available. In addition, sometimes the numbers were quite small. There were 151 preterm births, however, 129 complete birth records were available for the study. Perinatal and neonatal data were collected retrospectively from available patient records stored at MHWH using preformed data collection sheets by pediatric trained doctors.The neonatal variables incorporated gender (GEN), gestational age (GES), birth weight (BWG), necrotizing enterocolitis (NEC) , and the length of time on the ventilator (LTV), whilst the maternal variables were maternal age (MAT), gravidity (GRA) and obstetric complications (COM).p-value < 0.05 was taken as statistically significant. Confidence intervals were also calculated.The data were entered, coded and analyzed using SPSS  computer software program. Binary logistic regression was done. All variables listed above were binary with the exception of length of time on the ventilator. The Receiver Operating Characteristic (ROC) curve is a useful way to assess the performance of classification schemes in which there is one variable which is classified into two categories . The areEthical approval and clearance were obtained from the University of the West Indies as well as the North Central Regional Health Authority since this analysis used entirely registered data (CEC047/11/15). Furthermore, confidentiality and anonymity were assured by analyzing and disseminating the findings in aggregate.Preterm births (<37 weeks gestation) in this population consisted of 59% males and 41% females. Of these, 76 (59.7%) were moderate to late preterm (33 to <37 weeks), 43 (33.3%) were very preterm (28 to <32 weeks) and 9 (7.5%) were extremely preterm (<28 weeks). Birth weight ranged from 725 to 2900 g (standard deviation (SD): 485.6 g), maternal age from 17 to 43 years (SD: 6.6 years) and gravidity from 1 to 8 pregnancies (SD: 1.7 pregnancies).Among the neonates, the length of time on the ventilator ranged from 1 to 71 days. However, the length of stay ranged from 1 to 164 days (SD: 24.4 days) with an average of 21.7 days. Overall, 16 infants (12.4%) died before being discharged, and 11.6% (15) survived with disability evident at discharge.Among the maternal and neonatal variables considered, only neonatal variables were significantly correlated with preterm neonatal mortality i.e., birth weight, gestational age and respiratory distress syndrome. The results for the univariate analysis of maternal and neonatal characteristics of the subjects in relation with preterm neonatal mortality are summarized in The list of obstetric complications was also analyzed and is shown in Binary logistic regression was done to show the association between maternal and neonatal variables in relation to preterm neonatal mortality.p = 0.004) and very low to extremely low birth weight  were identified as significant risk factors for preterm neonatal mortality  = 1.09, Confidence Interval (CI): 1.03–1.15, ortality .The area under the ROC curve is 0.904 as shown in GEN = 0.1; GES = 0.1; BWG = 0.1; NEC = 0.1.The binary logistic regression model for the neonatal variables isp = 0.04) was the only significant risk factor for preterm neonatal mortality.The area under the ROC curve is 0.698 as shown in MAT = 0.1; COM = 0.1; GRA = 0.1.The binary logistic regression model for the maternal variables isThe investigation utilized the binary logistic regression and the study encompassed all neonates delivered at gestational age less than 37 weeks and admitted to the NICU at MHWH for the year 2015. There were 151 preterm births, however, 129 complete birth records were available for the study.The area under the ROC curve  is 0.904However, for the maternal model, the area under the ROC curve  is 0.698The results achieved from this single tertiary centre study will provide information about preterm neonatal mortality and will aid in achieving the millennium development goal of reducing under-five mortality by 2015 and beyond . Even thFinally, the research will hopefully provide relevant information that may serve as a starting basis for those who may wish to conduct further as well as longer term research, relating to preterm neonatal morbidity and mortality.p = 0.010) relative to birth weights between 1500 g and 2500 g is 2.74, i.e., the neonatal mortality is inversely proportional to birth weight. The latter result is similar to previous studies [Limitations of the study entailed its small sample size and the short time period of one year for the study. Nonetheless, this is the first step in the interpretation and statistical analysis of the data with relevance to the country of Trinidad and Tobago. The logistic regression model for the neonatal variables comprised of gender, gestational age, birth weight, necrotizing enterocolitis and the length of time on the ventilator. This study demonstrated that the log-odd value, β, for birth weights < 1500 g  increased the predicted counts of mortality by 1.09. Poor postnatal lung function resulted in both increase morbidity, and that increased length of time on the ventilator also having an adverse association with neonatal outcome.In 2007, the Institute of Medicine (U.S.) Committee reported that infants born before 30 weeks gestation lacked alveoli, as a result of underdeveloped lungs there was the need for assistance to breathe . The preAccording to a similarly represented study by Onuanaku et al., gender is not a significant predictor of neonatal mortality , this rep > 0.05)). This result may be driven by the considerably low neonatal deaths (n = 16) in our data set. However, the logit model predicted an 11% increase in mortality for neonates born with NEC relative to those without the disease.Although the leading cause of death in preterm births is NEC , our stuThe number of obstetric complications proved to be the only significant predictor of mortality in the maternal model . Yego et al. found that the risk of early neonatal death was higher for mothers who experienced PROM, haemorrhage and dystocia whereas the other cases of complications  had no significant effect . Our stup = 0.86) relative to mothers (age < 19) in association with neonatal mortality. Births to mothers between 19 and 35 years had a higher risk  of mortality compared to the reference category in this data set. This is indeed unusual and this may be an artifact of our small sample size. This study is preliminary in nature and provides the foundation for further work to address these perceived anomalies.According to Bin Pak and Horiuchi maternal age is not a neonatal mortality risk factor; our study also observed the same result . The stup = 0.77) as a determinant of preterm neonatal death, the latter results were also reported by Yego et al.According to Kurdi et al. preterm birth remains the most serious complication of multiple gestations . In our The strength of our analysis is the use of the outcome information collected before or around the time of birth. There are some limitations of the study: missing neonates’ records, the time period of one year and the consequent small sample size.A valuable extension to this study is to include other NICUs in Trinidad and Tobago. A longitudinal study will also be able to reveal trends. Furthermore, it will be interesting and useful for future studies to include individual obstetric complications especially those related to lifestyles. Finally, this study presents a snapshot of the present state of affairs at one of the hospitals in Trinidad and Tobago. We are cognizant of the fact that the results of the study cannot be generalized to the entire population of newborns in Trinidad and Tobago. However, the study does present sufficient information to make decision makers more aware of the factors that contribute to mortality in the NICU at MHWH. This can lend itself to better resource allocation and preventative measures being instituted.The neonatal variables birth weight and length time on the ventilator, as well as obstetric complications , proved to be risk factors of preterm neonatal mortality. However, gender, gestational age, necrotizing enterocolitis, maternal age and gravidity proved to be insignificant variables. Further work needs to be carried out to address these unusual occurrences.The neonatal and maternal models can be useful in providing useful descriptive information with regard to outcome expectations of the neonates admitted to the NICU at MHWH.


Postoperative pseudoaneurysm formation is one of the most feared complications of pancreatic leak following pancreaticoduodenectomy (PD). Surgical repair may be compromised due to a persistent enzymatic insult on the repaired vessel; therefore, preventive measures should be adopted. We report a case of ruptured hepatic artery pseudoaneurysm occurring 12 days following PD in a patient with a postoperative pancreatic fistula. Emergency surgery revealed that the pseudoaneurysm was situated at the point of surgical transfixation of the gastroduodenal artery. The pseudoaneurysm was successfully managed by under-running of the bleeding point combined with the direct application of hemostatic products to the bleeding surface (TachoSil and Tisseel to act as a barrier from the pancreatic secretions.


Neonatal sepsis is associated with abnormal neurodevelopmental outcomes but not with poor growth at 9 to 15 months of corrected age in LBW infants. This is a prospective cohort study involving 128 eligible preterm low-birth-weight (LBW) infants admitted during the period of 2013-2014 to the Durgabai Deshmukh Hospital and Research Center. All patients were followed up in the outpatient Department of Pediatrics. They were divided into the sepsis and nonsepsis group. A total of 94 infants were evaluated (40 in sepsis and 54 in nonsepsis group). At the age of 9–15 months, low-birth-weight infants with neonatal sepsis had an increased risk of neurodevelopmental disorders ). There is no statistically significant difference in the growth outcomes. Neonatal infections are associated with the abnormal neurodevelopmental outcomes in LBW infants but there was no significant difference at growth outcome at 9 to 15 months of corrected age between both groups.  Low-birth-weight (LBW) infants are at risk for poor growth and neurodevelopment outcome. In India, few studies are done showing the outcome between the very-low-birth-weight (VLBW) infants –3. In InIn year 2010, 15 million infants were born preterm worldwide. Out of these, 13 million were survived and 2.7% had moderate-to-severe neurodevelopment impairment . IntrautMany LBW and ELBW infants have at least 1 episode of early-onset or late-onset infection during their initial hospital stay. Neonatal infections and necrotizing enterocolitis (NEC) have been linked with an increased risk of neurodevelopment impairment in LBW survivors . HoweverIt is a prospective observational cohort study which is done in the year of January 2013 to December 2014 in Durgabai Deshmukh Hospital and Research Center, Hyderabad, India. All preterm LBW neonates with gestation ≤ 37 weeks born between January 2013 and December 2014 and discharged from the hospital were eligible for the study. Parental consent was obtained at the time of visit to the hospital for enrollment into the study for the long-term follow-up. The study was approved by the institute Ethical Committee. Infants with major congenital malformations, severe perinatal asphyxia (5 min Apgar < 4 and/or cord Ph < 7.0), and postneonatal meningitis or other CNS infections were excluded. A convenient sample size of 40 was taken due to financial and academic constraints. The study was continued till we got 40 neonates with sepsis.A total of 120 eligible preterm LBW infants (less than 37 weeks and birth weight ≤ 2500 grams) were admitted in the hospital. Five infants died in the NICU before discharge. Five babies had 5 min Apgar ≤ 5. Two infants were diagnosed to have meningitis and 2 infants required syndrome evaluation. Thus, a total of 106 infants were discharged alive from the NICU and were eligible for long-term follow-up. Of these, 44 babies had screen and/or culture positive sepsis and 62 babies were control group. After 9 to 15 months of corrected age 40 infants in sepsis and 54 infants in control group were evaluated. Four babies in the sepsis group and 8 babies in the control group are lost to follow-up.A total of 94 preterm infants with birth weight ≤ 2500 grams were available for analysis of outcome (40 in sepsis and 54 in nonsepsis group). All patients were born with less than 37 weeks of gestational age . These infants were followed up in a neurodevelopment center at the outpatient unit of the Department of Pediatrics.Growth is measured and depicted in terms of weight, length, and head circumference. Growth below the 5th centile when plotted on the Indian Academy of Pediatrics charts was considered as abnormal. For international comparison, growth below the 5th centile when plotted on the CDC functional growth charts was considered as abnormal see .Cerebral Palsy (CP). It is a group of permanent, but not unchanging, disorders of movement and/or posture and of motor function, which are due to a nonprogressive interference, lesion, or abnormality of the developing/immature brain as defined by Surveillance of Cerebral Palsy in Europe (SCPE) definition. CP is defined by the presence of any one of the following: hemiplegia or diplegia or quadriplegia and/or presence of dystonia as assessed during neurological examination. Visual Impairment. It is defined as blindness in one or both eyes or need for corrective lenses. Hearing Impairment. It is defined as requirement of hearing aids in one or both ears. Developmental Delay. It is defined as more than 2 delays in any sector on the Denver Developmental Screening Test II (DDST II).Tone Abnormalities. They are abnormal tone of any limb, either hypotonia or hypertonia requiring physiotherapy without gait abnormality and not qualifying for the definition of cerebral palsy.Osteopenia of Prematurity. It is defined as the presence of clinical features of rickets like Harrison sulcus, frontal bossing, wide anterior fontanel, and/or widening of wrist along with X-ray or biochemical changes . Hyperreactive Airway Disease. It is considered when there were at least two documented episodes of wheezing requiring inhaled steroids or bronchodilators with/without systemic steroids. Hospital Readmissions during Infancy. It is one or more admissions after discharge from the hospital for any illness.Gestational age was determined by first-trimester ultrasound scan. When the scan was not available it was based on mother's last menstrual period. The antenatal and perinatal details of enrolled infants were collected retrospectively from case files. This data included maternal demographic and clinical details and pregnancy related illnesses, antenatal steroid administration, and mode of delivery.Relevant neonatal data of all LBW babies including morbidity and mortality during the hospital stay was recorded in a predesigned proforma at the time of discharge from the hospital. Recorded data included birth weight, sex, and the need for resuscitation at birth and Apgar scores at 1 and 5 minutes. Incidence of Respiratory Distress Syndrome (RDS), Patent Ductus Arteriosus (PDA) clinical presentation or echocardiography proven for hemodynamically significant cases , sepsis 3), and Absolute Neutrophil Count (ANC) (<1000/mm3) and an Immature-to-Total neutrophil count (I : T ratio) > 0.2 with or without culture positivity. Elevated C reactive protein (CRP) (>10 mg/dL) is also included as marker of screen positive sepsis. The babies without culture positivity will be considered as screen positive sepsis.Sepsis is defined as having clinical suspicion with elevated White Blood Cells (WBC) count with predominance of immature granulocyte, polymorphonuclear cells (PMN) counts, depressed total White Blood Cell (WBC) count  and a Brain Stem Evoked Response Audiometry (BERA). At each visit babies were evaluated for growth and neurodevelopmental outcomes.At each visit growth was evaluated by measuring the weight and head circumference and length. Weight was recorded by an electronic weighing scale corrected up to 2 decimals. Length was measured using an Infantometer by extending the legs and keeping the ankle in neutral position. Head circumference was measured with a nonstretchable tape.Neurological assessment was done by Amiel Tison method. Developmental assessment was done using the Denver Development Screening Test II (DDST II) which assesses development in gross and fine motor, language, and social adaptive skills.t-test was used for continuous variables. Predictor variables associated with abnormal outcomes were also studied. Relative risks (95% CI) were calculated for primary and secondary outcomes.All the outcome variables were compared between the study and each of the control groups separately. Statistical analysis was performed by using the Statistical Package for the Social Sciences . Chi square test was used for categorical variables and independent Student Baseline data for 94 infants were included in the study; mean gestational age at birth was “SD + 2.03” weeks. Eighty-one (86.17%) infants were born through emergency caesarian section and 13 (13.82%) were born by spontaneous normal vaginal delivery. Eighty-one (86.17%) infants were given course of antenatal steroid. Seventy-seven (81.91%) were products of singleton pregnancies. Sixty-one (64.89%) infants were complicated by maternal hypertension. Oligohydramnios was present in 27 (28.72%) pregnancies, and seventeen (18.08%) babies were IUGR during pregnancy. Twenty-one (22.34%) infants were delivered prematurely because of preterm labor and 19 (20.21%) infants' mothers had preterm premature rupture of membrane. The above data is presented in Of 94 eligible LBW infants who were discharged alive from the hospital, median birth weight was 1883 grams (IQR1560–2360), and 46 (48.93%) were female infants. Fourteen infants (14.89%) had birth asphyxia (but Apgar > 5 at 5 min) requiring resuscitation, and 41 (43.61%) infants were diagnosed to have HMD. Fifty-four (57.44%) infants and 21 (22.34%) infants required CPAP and ventilator support during their NICU stay due to respiratory distress, respectively. Nineteen (20.21%) infants had NEC, 48 infants (51.06%) had features of shock requiring fluid bolus or inotropes support, 9 infants (9.57%) had hypoglycemia requiring intravenous dextrose infusion, 8 infants (8.5%) had seizures, and 14 infants (14.89%) received at least one blood transfusion for anemia. 11 infants (11.70%) were diagnosed to have clinical or 2D-Echo proven PDA, and, of these, 7 infants were treated with Indomethacin or oral Ibuprofen for PDA closure. Forty babies (42.55%) were diagnosed to have sepsis. Among them culture positive was seen in 24 infants (25.53%) and only screen positive sepsis was present in 16 infants (17.02%). The above data is presented in n = 94) the mean time to achieve full enteral feeds in the study group was 7.88 (SD ± 3.11) days. The mean duration of hospital stay was 17.67 (SD ± 10.63). The mean weight, mean head circumference, and mean length at discharge were 1999 (SD ± 114), 29.51 (SD ± 1.72), and 39.15 (SD ± 1.80), respectively. Seventeen infants (18.08%) had Retinopathy of Prematurity and of these 4 (23.52%) required laser therapy.Among the surviving infants (Twelve infants (12.76%) had abnormal BERA, and of these 4 (33%) required hearing aids. 30 (31.91%) babies had abnormal NSG at term corrected age. The above data is presented in Of the total 94 infants followed up at corrected age of 9 to 15 months, 40 infants had sepsis and 54 infants were without sepsis as control group. On comparing the sepsis group with control group the mean gestational age and mean birth weight were equal in sepsis group (mean GA 30.275 (SD ± 2.20) WK versus mean 31.25 (SD ± 1.86) Wk and mean birth wt 1706 (IQR1560–1880) gms versus mean birth wt 2060 (IQR 1650–2360) gms, resp.). The sex ratio and maternal variables such as PIH (67.5% versus 62.9%), gestational DM (15% versus 9.2%), hypothyroid (15% versus 18.1%), and APH (2.5% versus 7.4%) were similar in both the groups. The incidences of preterm PPROM (27.5% versus 14.8%), preterm labor (15% versus 27.7%), and antenatal oligohydramnios (32.5% versus 25.92%) were also similar in both the groups. Antenatal steroid coverage (90% versus 83.30%) and mode of delivery by LSCS were also similar in both groups (87.5% versus 85.18%). The resuscitation required in the septic group is significantly higher (30% versus 7.4%) as compared to control group. These data are presented in Tables Almost most of the neonatal morbidities were significantly higher in sepsis group, except HMD, CPAP, and HFO which were comparable in both groups. Tables During infancy, at 6 months of chronological age, 44 infants (46.80%) continued to be on exclusive breastfeeds, and 36 (38.29%) infants were on mixed feeds (breast feeds and formula milk). The median time of weaning or starting of solid supplements was 5 months of chronological age. In the majority of infants the weaning diet was a mixture of homemade diet and commercial weaning foods available in the market. The above data is presented in At the age of 9–15 months a total of 38 infants (40.42%) had abnormal neurological outcome, 7 (7.44%) had cerebral palsy, and 4 babies (4.2%) had deafness requiring hearing aids. 18 infants (19.1%) failed DDST II, 6 infants (6.3%) had squint, and 4 infants (4.2%) had blindness.p < 0.72). Also incidences of small head (<3rd centile in WHO growth charts) and short stature (<than 2 SD on WHO growth charts) in both the groups were comparable  had weight less than the 5th centile. Nine infants (9.5%) and 19 infants (20.21%) had head circumference and length less than the 5th centile, respectively . When plmparable .The abnormal neurological outcome constitutes the infants with cerebral palsy, infants requiring hearing aids, infants who failed DDST, and infants who had squint and blindness. Number of infants evaluated between 9 and 12 months in sepsis and control group was 26 (65%) and 33 (61.1%), respectively, and infants evaluated between 12 and 15 months in sepsis and control group were 14 (35%) and 21 (38.8%), respectively.p < 0.001). The data is presented in Comparing the outcomes between the two groups the outcome of abnormal neurological examination was significantly more in sepsis group than in control group  = 36.9%; p = 0.06) between the studies was significant and related to variations in patient characteristics, causative pathogens, and follow-up methods [In a systematic review and meta-analysis, comparing neurodevelopmental outcomes in VLBW infants exposed to culture-proven sepsis in the neonatal period with similar infants without sepsis, 15,331 infants were evaluated. Sepsis in VLBW infants was associated with an increased risk of one or more long-term neurodevelopmental impairments (odds ratio (OR) 2.09; 95% confidence interval (CI) 1.65 to 2.65) including cerebral palsy . Heterogeneity ( methods .p  0.014) as compared to control group; however in comparison with other studies there was no significant difference in OFC and length at 9 to 15 months as our study did not have power to pick up the difference.Mukhopadhyay et al.  conductep  0.001) and also found that there is a gap between the high technology and quality of medical care and loss of or no neurodevelopmental care for high risk neonates and infants in NICUs by specialties and nursing of long-term neurodevelopmental outcome for high risk neonates. Modi et al. [The premature infants are at risk of major and minor deficits such as cerebral palsy, cognitive and speech delays, motor and visual deficits, psychosocial and behavioural disorders and dysfunction at school. Soleimani et al.  conductei et al.  evaluateNeonatal sepsis are associated with abnormal neurodevelopmental outcomes but not with poor growth at 9 to 15 months of corrected age in LBW infants. However, these associations should be studied in different settings with larger sample sizes.


Apo A-I deficiency clinically shows low serum levels of HDL cholesterol and corneal opacity at a young age. Histopathological evaluations of affected corneas are not enough, and the mechanism of corneal opacity is still unclear.Tsukuba was identified. Histopathological examination of the corneal button after PKP showed numerous vesicles in the corneal stroma, which were more prominent in the deep stroma than in the shallow stroma. Collagen VI was observed in some of those vesicles.A 61-year-old woman suffered from blurred vision with a corneal opacity. She had significantly reduced serum levels of high-density lipoprotein cholesterol and Apo A-I, stenosis of the coronary arteries, and ischemic heart failure. On genetic examination, a homozygous mutation of Apo A-IWe experienced a rare case of corneal opacity due to Apo A-I deficiency. Our histopathological findings indicated that structural changes in corneal collagen fibrils contribute to the formation of stromal vesicles. Apo A-I is an essential component of HDL. Its deficiency is clinically detected by low serum levels of HDL cholesterol. Although different gene mutations of Apo A-I are reported –4, the tIn 2012, a 61-year-old woman with blurred vision presented with corneal opacity of the left eye. Her visual acuity was 20/40 OS and 20/20 OD. She had been diagnosed with HDL deficiency at the age of 46 years, 1997. but she had been off treatment for about 10 years. She had undergone PKP of the right eye for the same symptoms when she was 58 years old, 2009.The patient was the fourth of 8 siblings. A brother died in an accident and a sister died in childhood. None of her family members had been diagnosed with HDL deficiency, and there was no family history of consanguineous marriage. On physical examination, she had bilateral xanthomas of the eyelids and focal yellow skin discolorations in the cubital fossae of both forearms, but there was no tonsillar hypertrophy or Achilles tendon xanthoma.Tsukuba mutation, which is a single-nucleotide insertion of cytosine that alters the reading frame from codon 5 and produces a premature stop codon at codon 34  with undetectable Apo A-I (<5 mg/dL). Levels of Apo B and Apo E were slightly elevated . Serum triglyceride, total cholesterol, low-density lipoprotein cholesterol, and lecithin-cholesterol acyltransferase levels were within the normal limits. A genetic evaluation was performed as previously described , and shoOn slit-lamp examination, there was a diffuse corneal stromal opacity with a lucid zone in the left eye. Confocal microscopy  revealed high-intensity vesicles (10–100 μm in diameter) in the corneal stroma Fig. . In 2013The cornea showed normal thickness and there was no significant abnormality of the epithelium, Bowman’s layer, or the endothelium. There were numerous small vesicles in the corneal stroma Fig. , which wSince the PKP, the patient has been on regular medication with pitavastatin and tocopherol nicotinate and has had a normal lipid profile except for low serum HDL-cholesterol levels. In 2015, her current visual acuity is 20/25 OS and 20/20 OD and both corneal grafts have maintained good transparency.Iowa, are known to induce amyloidosis [Our patient demonstrated clinical findings typical to Apo A-I deficiency. Histopathologically, vesicles in the corneal stroma were significantly larger (10–100 μm in diameter) than those described in the report by Osakabe and colleagues (200 nm–2 μm in diameter) . Apo A-Iloidosis . HoweverCollagen VI is a major extracellular matrix protein, bridging cells to the surrounding connective tissue and organizing the three-dimensional tissue architecture. The mutations in the genes encoding Collagen VI chains result in several forms of inherited myopathies, decrease of stiffness in cartilage . It is aTo our knowledge, ours is the first report of a patient with confirmed mucoid degeneration and accumulations of collagen VI in the stromal vesicles. Our results suggest that structural changes in corneal collagen fibrils contribute to the formation of stromal vesicles.


Advanced levels of delivery room resuscitation in very low birth weight infants are reported to be associated with death and complications of prematurity. In resource limited settings, the need for delivery room resuscitation is often used as a reason to limit care in these infants.This was a review of delivery room resuscitation in very low birth weight infants born in a tertiary hospital in South Africa between 01 January 2013 and 30 June 2016. Outcomes included death and serious complications of prematurity. Advanced delivery room resuscitation was defined as the need for intubation, chest compressions or the administration of adrenaline.p < 0.001). Advanced delivery room resuscitation was significantly associated with a 5 minute Apgar score < 6 (OR 13.8 (95%CI 8.6–22.0), supplemental oxygen at day 28 (OR 2.2 (95% CI 1.4–3.9), metabolic acidosis (OR 2.3 (95% CI 1.1–4.8) and death (OR 1.9 95% CI 1.1–3.3). Other serious complications of prematurity were not associated with advanced delivery room resuscitation. Mortality was increased in infants with a low admission temperature (35.1 °C (SD 0.92) vs 36.1 °C (SD 1.4) (p < 0.001).A total of 1511 very low birth weight infants were included in the study. The majority (1332/1511 (88.2%) required oxygen in the delivery room. Face mask ventilation was needed in 45.2% (683/1511). Advanced delivery room resuscitation was only required in 10.6% (160/1511). More than half the infants who required advanced delivery room resuscitation died . Advanced delivery room resuscitation was required in significantly more infants <1000 grams at birth than those infants >1000 grams (83/539 (15.4%) vs 77/972 (7.9%) There was a high mortality rate associated with advanced delivery room resuscitation; however complications of prematurity were not increased in survivors..The need for advanced delivery room resuscitation alone should not be used as a predictor of poor outcome in very low birth weight infants. Survivors of advanced delivery room resuscitation should be afforded ventilatory support if required. Special care must be taken to avoid hypothermia in very low birth weight infants requiring resuscitation at birth. Perinatal asphyxia is an important cause of morbidity and mortality, especially in low and middle income countries. In a review in South Africa in 2007, one third of neonatal deaths were due to asphyxia – hypoxia . In termHypoxic ischaemic brain injury in preterm infants is less well defined than in their term counterparts; the extent and type of brain damage depends on brain immaturity, cellular vulnerability and the timing and intensity of the asphyxial insult . AdvanceSouth Africa is a middle income country with limited health funding and resources. There are insufficient neonatal ventilator facilities to provide mechanical ventilation to all those VLBWI who require it. In order to address this problem, mechanical ventilation was rationed to those VLBWI above 1000 grams at birth, based on the premise that extremely low birth weight infants (ELBWI) with a birth weight below 1000 grams have a poor outcome. More recently, however, there has been a move away from using a birth weight cut off alone for mechanical ventilation in VLBWI . AlthougResuscitation at birth has been reported to be associated with mortality in VLBWI in South Africa . There iThis study was conducted in the neonatal unit in a tertiary referral centre, between 01 January 2013 and 30 June 2016. All inborn VLBWI were included in the study. Infants with no record of resuscitation and those with lethal congenital abnormalities were excluded.Delivery room resuscitation was classified as none, oxygen only, positive pressure ventilation, endotracheal intubation, chest compressions and administration of adrenaline. “Oxygen only” referred to blow –by oxygen. If the infant did not respond to supplemental oxygen alone, oxygen would then be provided using positive pressure ventilation with a T piece resuscitator. An air oxygen blender was not available in the delivery room during the time of the study. A baby could have had all levels of intervention and was analysed accordingly. All VLBWI were wrapped in plastic wrap and resuscitated under a radiant warmer. The delivery room temperature was set at 25 °C.The study site was a tertiary referral centre for both high risk obstetric and neonatal cases. The neonatal unit comprised two areas – a neonatal intensive care unit (NICU) where mechanical ventilation was provided and a premature nursery where VLBWI were treated with surfactant and NCPAP. There were 32081 live births during the study period and the overall Caesarean section (C section) rate was 48.1%. Uncomplicated preterm labour alone was not an indication for C section. Elective C section referred planned delivery by C section e.g. for previous C section and malposition. Spinal anesthesia was routinely used during the study period. Primary indication for C section was recorded.Preterm deliveries were attended by an intern who was supervised by a registrar. An intern was a newly qualified doctor doing compulsory training in the paediatric unit, as part of a general practical training. A registrar was a doctor specializing in paediatrics. All registrars were completing a 4 year rotation in paediatrics and all had at least 18 months of paediatric experience prior to commencing the registrar rotation. Both registrars and interns were trained in neonatal resuscitation. The intern would initiate neonatal resuscitation and call the registrar for assistance as required. Resuscitation was initiated in all VLBWI irrespective of birth weight, unless there was a known diagnosis of intrauterine fetal death. Resuscitation could be discontinued after 10 minutes of asystole, in consultation with a senior member of staff.All VLBWI were admitted to a transitional delivery ward nursery for initial evaluation and stabilization; VLBWI were then transferred to the premature nursery or NICU as required. The duration of stay in the transitional nursery could last several hours before a bed in NICU or the premature nursery became available. Deaths that occurred in this transitional nursery or labour room were classified as delivery room deaths. Deaths that occurred within 12 hours of life included VLBWI who died in the delivery room, premature nursery or NICU. Due to limited resources (both staff and equipment), during the study period, surfactant and NCPAP were only provided to VLBWI weighing >750 grams at birth; mechanical ventilation was only provided to VLBWI > 900 grams at birth. A second dose of surfactant could be given if respiratory distress worsened in VLBWI <900 grams. There was no NCPAP or surfactant replacement therapy (SRT) available in the delivery room for resuscitation during the study period. The initial therapy for all VLBWI with respiratory distress syndrome (RDS) was SRT and NCPAP. The axillary temperature of all VLBWI was recorded on admission to the transitional nursery.All staff was trained in neonatal resuscitation according to the South African Neonatal Resuscitation Algorithm (SANRA) approved by the South African Resuscitation Council (www. resus.co.za) and the South African Paediatric Association. The SANRA is a single standardised protocol used for training all birth attendants – both nursing and medical. The SANRA states that intubation can be done at any point with a skilled operator, but most birth attendants in South Africa are midwives or junior doctors who are not skilled in endotracheal intubation. This protocol therefore emphasizes the need for proper face mask ventilation and de-emphasizes the need for intubation. Chest compressions were initiated prior to intubation and routine intubation for VLBWI was not recommended.This was a secondary analysis of an existing neonatal database, managed using Research Electronic Data Capture (REDCAP) software , hosted Data was analysed using IBM SPSS version 23. Continuous data was described using mean and standard deviation or median and range, as appropriate, according to the distribution of the data. Categorical variables were described using frequencies and percentages. Outcomes of interest were in hospital mortality or significant complications of prematurity including necrotising enterocolitis (NEC), ROP, IVH, supplemental oxygen at 28 days of life, postnatal steroids, RDS, SRT, NCPAP, mechanical ventilation, patent ductus arteriosus (PDA), neonatal sepsis, cystic periventricular leukomalacia (PVL). Diagnosis of PDA was confirmed on echocardiography by a cardiologist; NEC was defined as modified Bell stage 2 or 3  and IVH There were 2994 VLBWI admitted over the study period. There were 31 infants with congenital abnormalities, 11 infants had no recorded resuscitation, 1430 infants were born elsewhere and 11 infants had no recorded birth weight. The final sample therefore comprised 1511 VLBWI. The mean birthweight of VLBWI was1091.8 (SD260) grams and gestational age was 28.8 (SD 2.6) weeks. There were 539/1511 (35.7%) ELBWI. The majority of the VLBWI was female  and most were black . Other neonatal characteristics are shown in Table p < 0.001).Very few VLBWI did not require any DRR  and 10.6% (160/1511) received ADRR. The number of VLBWI in each level of DRR is shown in Table p < 0.001). Similarly, the gestational age of VLBWI who required ADRR was significantly less than those who did not (27.9 weeks (SD 2.7) vs 29.0 weeks (SD 2.7) p < 0.001). Other maternal and neonatal characteristics that were significantly associated with ADRR are shown in Table The mean birth weight of VLBWI who received ADRR was significantly lower than that of those who did not require ADRR (992.0 grams SD 255.4) vs 1105.1 grams (SD 256.3)  vs 1105.All other maternal and neonatal characteristics were not significantly associated with ADRR. In particular, admission temperature, NEC, ROP, PDA, IVH, cystic PVL, LOS, pneumothorax, pulmonary haemorrhage and the need for NCPAP or mechanical ventilation were not significantly associated with ADRR. The indication for C section was recorded in 649/961 67.5%) of VLBWI delivered by C section. There was no significant association between the indication for C section and the need for ADRR (see Table % of VLBWp < 0.001). There was no difference in mortality by gender – 210/685 (30.6%) males died compared to 229/822 (27.8%) females (p = 0.255). – The admission temperature of VLBWI who died was significantly lower than those who survived – 35.1 °C (SD 0.92) vs 36.1 °C (SD 1.4). (p < 0.001)Overall in- hospital mortality was 29.1% (439/1511); 78/439 (17.8%) of the deaths occurred in the delivery room. There were 87 of the 439 deaths (19.8%) that occurred within 12 hours of admission; the majority of these occurred within the delivery room . Significantly more ELBWI died compared to those with a birth weight > 1000 grams  (p < 0.001). More than half the VLBWI who required ADRR died .Mortality rates by level of resuscitation are shown in Fig. p < 0,001), lighter birth weight  and lower gestational age .Those VLBWI who required ADRR and died within the first 12 hours of admission were compared to those who survived for more than 12 hours. In this group, death within the first 12 hours was significantly associated with lower admission temperature  trial showed that BPD was significantly associated with ADRR .Admission hypothermia significantly increases the chance of death in very preterm infants , 20. In http://www.resus.co.za). Most birth attendants are midwives, so the training emphasises effective face mask ventilation, rather than intubation. In the SANRA, health workers who are not skilled in intubation are taught to intubate after chest compressions. Those VBLWI with RDS at birth would not be routinely intubated as NCPAP was the first line ventilatory support in the unit at the time of the study.In the present study, no major complications of prematurity, including ROP, NEC, IVH, cystic PVL, sepsis, pneumothorax, pulmonary haemorrhage or the need for ventilatory support were significantly associated with ADRR. This is in contrast to many other reports which have reported an increase in complications of prematurity in VLBWI who had ADRR –8. This Complications of prematurity were not increased in survivors of VLBWI who required ADRR. This suggests that survivors of ADRR should be provided with ventilatory support if required– the need for ADRR alone is not sufficient reason to ration care. Some other researchers have reported that the outcome of VLBWI following ADRR is not that bad. In a study from the Vermont Oxford Network in the late 1990s Finer et al. reported that most VLBWI undergoing ADRR survive and half did not have severe IVH . De MaurThere was a high mortality rate in VLBWI requiring ADRR in a tertiary centre with neonatal facilities. Although there is no available information, it is very probable that the mortality rate of VLBWI is even higher in non-tertiary centres where DRR may be sub-optimal. This emphasises the need for VLBWI to be delivered in a properly equipped tertiary centre, where possible. In addition, available staff in non-tertiary centres should be properly trained and equipped to carry out neonatal resuscitation.The retrospective nature of the study meant that some data was missing and could not be evaluated. More detailed information regarding the resuscitation e.g. dose of adrenaline, duration of chest compressions, number of attempts at intubation could not be evaluated. There was no record of the timing of cord clamping, so the effect of delayed cord clamping could not be determined. The benefit or otherwise of the seniority and experience of the attending staff members conducting the resuscitation could not be assessed. The number of VLBWI who had cranial sonars done was low due to resource constraints, so the incidence of IVH and PVL may be under estimated. Rates of death and complications are a poor proxy for the quality of resuscitation. A prospective study should be done to appraise the quality and effectiveness of DRR in VLBWI.The present study showed that mortality increased with advancing levels of delivery room resuscitation in VLBWI. Extremely preterm, small VLBWI were most likely to die after ADRR. Major complications of prematurity were not increased in those VLBWI who survived ADRR. All VLBWI who survive ADRR should be provided with ventilatory support if required; the results of the present study suggest that the need for ADRR alone is not sufficient reason to limit care in these infants in the study setting. The low complication rate, however, may be related to high mortality in this group of infants – improved survival may result in an increase in complications of prematurity. There must be careful monitoring of the outcome of VLBWI who are provided with ventilatory support.


To assess associations between unconventional natural gas development (UGD) and perinatal outcomes.We conducted a retrospective birth cohort study among 158,894 women with a birth or fetal death from November 30, 2010-November 29, 2012 in the Barnett Shale, in North Texas. We constructed three UGD-activity metrics by calculating the inverse distance-weighted sum of active wells within three separate geographic buffers surrounding the maternal residence: ≤½, 2, or 10-miles. We excluded women if the nearest well to her residence was >20 miles. Metrics were categorized by tertiles among women with ≥1 well within the respective buffer; women with zero wells ≤10 miles (the largest buffer) served as a common referent group. We used logistic or linear regression with generalized estimating equations to assess associations between UGD-activity and preterm birth, small-for-gestational age (SGA), fetal death, or birthweight. Adjusted models of fetal death and birthweight included: maternal age, race/ethnicity, education, pre-pregnancy body mass index, parity, smoking, adequacy of prenatal care, previous poor pregnancy outcome, and infant sex. Preterm birth models included all of the above except parity; SGA models included all of the above except previous poor pregnancy outcome.We found increased adjusted odds of preterm birth associated with UGD-activity in the highest tertiles of the ½- (odds ratio (OR) = 1.14; 95% confidence interval 1.03, 1.25), 2- , and 10-mile  metrics. Increased adjusted odds of fetal death were found in the second tertile of the 2-mile metric  and the highest tertile of the 10-mile metric . We found little indication of an association with SGA or term birthweight.Our results are suggestive of an association between maternal residential proximity to UGD-activity and preterm birth and fetal death. Quantifying chemical and non-chemical stressors among residents near UGD should be prioritized. Advancements in horizontal drilling and hydraulic fracturing have increased access to previously untapped natural gas reserves in shale formations. Unconventional natural gas development (UGD) is associated with several potential environmental hazards. The hydraulic fracturing process involves injecting a pressurized mixture of sand, water, and proprietary fracking fluid into wellbores, fracturing the rock and unlocking trapped hydrocarbons . FrackinResults of the few epidemiologic studies of the association between maternal residential proximity to UGD and perinatal outcomes are equivocal –21. AlthThis retrospective birth cohort study included women with a singleton birth or fetal death from November 30, 2010-November 29, 2012 in the 24-county Barnett Shale area , in North Texas. Birth and fetal death records were obtained from the Texas Department of State Health Services (TXDSHS) for 166,966 births and 866 fetal deaths. This study was approved by the Committee for Protection of Human Subjects at The University of Texas Health Science Center at Houston and the TXDSHS IRB.th percentile of the sex-specific weight for age distribution in our study sample. Preterm birth (yes/no) was defined as a live birth delivered before 37 completed weeks gestation. We identified fetal deaths from death records (yes/no). We obtained birthweight (g) from birth records and treated it as a continuous outcome.We corrected implausible birthweight for gestational age combinations for live births, according to methods previously described –25. For 2, 18.5–24.9 kg/m2, 25.0–29.9 kg/m2, 30.0–34.9 kg/m2, ≥35.0 kg/m2), infant sex, and previous poor pregnancy outcome . We also constructed the Adequacy of Prenatal Care Utilization Index  which captures timing of first prenatal visit and frequency of visits [Street-level geocoded location of maternal residence at birth was provided by TXDSHS  for the f visits . The ‘unf visits ), presumf visits .www.drillinginfo.com), a commercial site which maintains a national database of oil and gas well locations and characteristics (updated twice monthly) [We obtained UGD data from DrillingInfo (monthly)  on May 1monthly)  or produmonthly) . In thisWe constructed three separate exposure metrics by generating geographic buffers around each residence, at distances of ½, 2, and 10 miles. One-half mile was chosen on the basis of a previous risk assessment , 10 milea priori. We identified additional covariates separately for each outcome. Covariates which were statistically significantly (p<0.05) associated with the respective outcome were included in the final adjusted model. In this way, a common set of variables were included in all adjusted models for each outcome, irrespective of the UGD-metric, facilitating comparison across metrics. In addition to the a priori variables, education, parity, smoking status, infant sex, previous poor pregnancy outcome, and the Adequacy of Prenatal Care Utilization Index were included in models of birthweight and fetal death. The preterm birth models did not include parity and SGA models did not include previous poor pregnancy outcome.We used logistic regression to examine the relation between each UGD-activity metric and preterm birth, SGA, and fetal death and linear regression to examine the relation with birthweight. Given potential correlation among women within census-tracts, we applied generalized estimating equations to all models, assuming an exchangeable correlation structure and treating census tract as a random effect. We included maternal age, pre-pregnancy BMI, and maternal race/ethnicity in all models Given the association of maternal residential distance to the nearest major roadway with pregnancy outcomes in previous studies , we condWomen in this study were mostly young (31.5% were >30 years) with at least a high school education (79.1%) and did not smoke during pregnancy (95.6%) . HispaniThe proportion of women with ≥1 active UGD well near her residence during pregnancy varied by distance within which UGD was captured: 15.9% at ½ mile, 45.1% at 2 miles, and 75.8% at 10 miles. The median number of proximal wells during pregnancy increased with buffer size: three ≤½ mile, 28 ≤2 miles and 413 ≤10 miles. This divergence was more apparent at the extremes of the distribution: maximum wells ≤10 miles of the residence during pregnancy was >2,000, versus 32 wells ≤½ mile. We observed similar patterns in the distribution of IDW metrics .Crude associations between UGD-activity and preterm birth were largely null for each UGD-metric. After adjustment, we found increased odds of preterm birth associated with UGD-activity in the highest tertiles of the ½- (odds ratio (OR) 1.14; 95% confidence interval (CI) 1.03, 1.25), 2- , and 10-  mile metrics . The higWe found indication of weak inverse associations between UGD-activity and SGA within each distance in the crude models . Little nd tertile of the 2-mile metric . We observed the strongest association between UGD-activity and fetal death using the 10-mile metric. We observed increased adjusted odds of fetal death among women in each tertile of the 10-mile UGD-activity metric: 1st tertile OR 1.26 , 2nd tertile OR 1.22 , 3rd tertile OR 1.34 .Little evidence of association between UGD-activity and fetal death was observed in crude models . Though nd tertile of the ½- and 2-mile metrics, respectively. Infants born to women classified in the 1st and 3rd tertiles of the 10-mile metric had birthweights, on average, 7.36 g  and 6.56 g  less than infants of women in the referent group.Crude models between UGD-activity and birthweight revealed positive associations . HoweverNeither the additional adjustment for residential proximity to nearest major roadway nor season of conception resulted in meaningful changes to effect estimates  Tables.We found evidence of a moderate positive association between maternal residential proximity to UGD-activity and increased odds of preterm birth and a suggestive association with fetal death. Not surprisingly, we found that the characterization of UGD was dependent upon the distance within which activity was defined.rd tertile OR 0.91, 95% CI 0.85, 0.98) as well as a positive association with birthweight . The authors of that study defined UGD-activity based on active wells ≤10 miles of the maternal residence at any time during the child’s birth year. The authors also restricted the analysis to women in rural areas, given concerns of confounding by other sources of air pollution. A similar restriction was not feasible in the present study because the majority of UGD in the Barnett Shale occurs in urban/suburban areas. However, we did not observe meaningful changes in effect estimates when adjusting for proximity to the nearest major roadway, a marker for traffic-related air pollution.In contrast to our findings, a Colorado (CO) based study  reportednd , 3rd , and 4th  UGD-activity quartiles, but no association with SGA. Stacy et al. [Two studies of UGD and birth outcomes in Pennsylvania (PA) have conflicting results. Stacy et al.  employedy et al.  also fouy et al.  includedy et al. .Given key differences in drilling characteristics  as well as population characteristics, it is difficult to directly compare our results with previous studies’ findings. For example, there were 509 total active wells in the Stacy et al.  study anBoth air and water contamination have been linked with UGD-activity, including UGD in the Barnett Shale. For example, air pollution models indicate urban drilling is a significant contributor to ambient ozone in the Barnett Shale , which mEndocrine disruption has been suggested as a possible mechanism through which UGD-related contaminants may increase risk of adverse perinatal outcomes including stillbirth, preterm birth, and decreased birthweight , 41, 42.One of the strengths of this study was the large sample size, even when considering UGD-activity relatively close to women’s homes. Though it is a rare outcome, our large sample size allowed us to explore the association between UGD-activity and fetal death, which other studies have not considered. It is possible that women with preterm births or fetal deaths may be assigned lower values for UGD-activity than women with term births simply due to their shorter gestational periods. However, we anticipate that the result of any such bias would be toward the null. Because spatial autocorrelation can lead to biased estimates when using spatially derived data , we alsoThough the exposure metric utilized in this study was non-specific, our goal was not to examine risk related to any specific chemical. Rather, it was to examine effects of living near increased UGD-activity, which encompasses potential exposure to a multitude of chemical and non-chemical stressors, through a variety of pathways. Our use of proximity to UGD-activity assumes that women who reside near wells are more likely to be exposed (or to be exposed at higher levels) to these stressors than women living farther away. Still, there is some uncertainty regarding the ideal distance within which to capture UGD-activity.Prior studies evaluating maternal residential proximity to UGD and birth outcomes focused on UGD ≤10 miles of the maternal residence. However, we posit it may be more plausible for UGD-activity to affect perinatal outcomes  at a much smaller distance. Many air toxics, such as benzene, are highly volatile in the atmosphere and undergo degradation relatively quickly –thus emiWe found evidence of an association between maternal residential proximity to UGD-activity and preterm birth and limited evidence of an association with fetal death among a diverse population of women living near the Barnett Shale. Though there may be differences in air pollution emissions during completion and production phases of UGD drilling , 56, we S1 Table(DOCX)Click here for additional data file.S2 Table(DOCX)Click here for additional data file.


A short cervix in the second trimester of pregnancy is a risk factor for preterm birth. In specific patient cohorts, vaginal progesterone reduces this risk. Using 16S rRNA gene sequencing, we undertook a prospective study in women at risk of preterm birth  and preterm birth <34+0 weeks . In contrast, Lactobacillus crispatus dominance was highly predictive of term birth . Cervical shortening and preterm birth were not associated with vaginal dysbiosis. A longitudinal characterization of vaginal microbiota  was then undertaken in women receiving vaginal progesterone  versus controls (n = 42). Progesterone did not alter vaginal bacterial community structure nor reduce L. iners-associated preterm birth (<34 weeks).L. iners dominance of the vaginal microbiota at 16 weeks of gestation is a risk factor for preterm birth, whereas L. crispatus dominance is protective against preterm birth. Vaginal progesterone does not appear to impact the pregnancy vaginal microbiota. Patients and clinicians who may be concerned about “infection risk” associated with the use of a vaginal pessary during high-risk pregnancy can be reassured.The online version of this article (doi:10.1186/s40168-016-0223-9) contains supplementary material, which is available to authorized users. Lactobacillus species [Lactobacillus species; Lactobacillus crispatus (CST I), Lactobacillus gasseri (CST II), Lactobacillus iners (CST III), and Lactobacillus jensenii (CST V). CST IV describes microbial communities largely devoid of Lactobacillus species and enriched mainly in anaerobic bacteria (CST IV).Preterm birth before 37 weeks of gestation is now the leading cause of death among children under the age of five . An esti species , 9. Thes species . Assessm species –13. A coLactobacillus species [Lactobacillus species abundance and stability with advancing gestation and a decline in the number of women harboring microbial communities void of lactobacilli, with a dramatic change to reduced Lactobacillus dominance and increased diversity following estrogen withdrawal in the post-partum period [Lactobacillus spp. depletion and vaginal dysbiosis and poor pregnancy outcomes including preterm birth [L. iners dominance rather than dysbiosis for preterm birth risk in pregnancy [L. iners is a vaginal commensal that has relatively recently been shown to be associated with dysbiosis [The composition of vaginal CSTs appears to be influenced by endogenous hormones, fluctuating with menses , the use species . This sum period , 19. Therm birth , which arm birth . This marm birth , 23. Thirm birth , 24. Recregnancy . L. inerysbiosis , 27 and ysbiosis .The cervix serves as both a mechanical and chemical barrier to ascending bacteria . PrematuThe mechanism of action of vaginal progesterone in the prevention of preterm birth involves its capacity to promote anti-inflammatory and pro-relaxant pathways in the uterus thereby reducing uterine contractility –43. EndoLactobacillus spp. dominance and stability, given progesterone’s anti-inflammatory properties, and efficacy for preterm birth prevention. We therefore undertook a prospective study in women at high-risk of preterm birth to assess (1) the relationship between vaginal microbiota in the second trimester and the risk of preterm birth and (2) the impact of vaginal progesterone therapy on the vaginal microbiota in women with a short cervix.We hypothesized that progesterone supplementation would promote The study was approved by NHS National Research Ethics Service (NRES) Committee London - City and East REC 12/LO/2003), and all participants provided written, informed consent at enrolment. A workflow of the study is provided in Additional file 2/LO/2003+0 days) were prospectively recruited from the preterm surveillance clinics at two tertiary London maternity units between January 2013 and August 2014. At initial attendance of preterm surveillance clinics at 16 weeks of gestation, cervico-vaginal fluid was sampled from the posterior fornix under direct visualization, using a BBL™ CultureSwab™ MaxV Liquid Amies swab . The vaginal swabs were placed immediately on ice before being transferred and stored at −80 °C within 5 min of collection. A cervical length (CL) measurement was taken by transvaginal scan (TVS) in supine position, with an empty bladder, taking care to avoid undue pressure on the cervix. Metadata collected included gestation age at sampling, subsequent interventions for preterm birth, gestation at birth, BMI, ethnicity, and antibiotics within the week preceding sampling. Participation in this study did not influence subsequent clinical care or dictate preventative interventions  for preterm birth risk. For the duration of the study, both units employed a policy of CL screening every 3 weeks until 25 weeks, with the indication for intervention being a CL <25 mm at TVS measured at ≤23+6 weeks gestation. In this cross-sectional arm of the study, the choice of intervention for a short cervix (cerclage or progesterone) was at the discretion of the attending clinician.To investigate the association between the vaginal microbiome, cervical length, and preterm birth outcome, a cross-sectional cohort of singleton pregnancies at higher than normal risk of preterm birth , iatrogenic preterm birth, HIV positive women, and women who had had sexual intercourse or vaginal bleeding in the preceding 48 h. In the longitudinal study, any women receiving cervical cerclage in either the progesterone or control groups were excluded as this may adversely impact on vaginal microbiota [Eligibility criteria for participation in both cross-sectional and longitudinal studies included women with a singleton pregnancy and a prior spontaneous preterm birth <37 weekswww.arb-silva.de/) used for sequence alignment. Sequence classification was performed using the RDP database reference sequence files and the Wang method [n = 725) [DNA extraction from BBL™ CultureSwab™ was performed as previously described . Forwardg method  and taxog method  for specn = 725) .L. crispatus), II (L. gasseri), III (L. iners), IV , and V (L. jensenii) as described by Ravel et al. [Examination of statistical differences between vaginal microbiota was performed using the Statistical Analysis of Metagenomic Profiles (STAMP) software package . To clasl et al. .+0 weeks, 34+0 to 36+6 weeks, and ≥37+0 weeks, using a 2-way ANOVA.In the cross-sectional cohort, a total number of species observed and the Shannon index of alpha diversity were calculated and compared across gestation at birth: <34P value that is less sensitive to small sample sizes than alternative approaches such as Chi-squared (reference). Fisher’s exact test was also used to examine individual CST assignments . Gehan-Breslow-Wilcoxon test was used to compare pregnancy survival (duration of gestation) for CST I compared to CST III [Examination of the relationship between vaginal bacterial communities (or CSTs) and cervical length or preterm birth was assessed using a Fisher exact test as to provide an exact, robust  CST III .P values for each analysis [A logistic mixed-effects regression analysis incorporating gestational age at sample, maternal age, and BMI as fixed effects and ethnicity as a random effect was performed to assess the relationship between pregnancy outcome (birth <34 and >34 weeks) and CSTs as well as individual species abundance. Analyses were performed in R using ANOVA and the “glm”  R function to analyze the table of deviance for CSTs and for individual species (present in >5% of samples). Species abundances were log-transformed, adjusted for confounders, and false discovery rate adjustment (Benjamini-Hochberg) was applied to correct analysis .+0 weeks according to CST classification at 16-week sampling.Accuracy parameters, sensitivity (sens), specificity (spec), positive predictive values (PPV), and negative predictive values (NPV) were calculated for the prediction of preterm birth <34P value and F statistics) were calculated using ANOVA with Satterthwaite approximation for degrees of freedom. For each fixed-effects term, a false discovery rate adjustment (Benjamin-Hochberg) was applied to correct P values. All data and computational approaches used for this study are provided in additional information , and cohort  as fixed-effects and the anonymized patient ID as uncorrelated random-effect was used to assess the impact of progesterone intervention on CST distribution and relative abundance in species present in >5% of all samples. The contributions of fixed-effects terms . Rates of preterm birth <37+0 weeks were higher in Black women  than Caucasians  and Asians . Subsequent cervical shortening to below 25 mm occurred in 66% (91/161), all of whom went on to receive an intervention .A total of 161 pregnant women attending prematurity surveillance clinics for their first appointment , intermediate , and dysbiotic  or term birth . Of those women delivering preterm, 3/34 (9%) harbored a dysbiotic or intermediate microbiome at 16 weeks compared to 6/127 (5%) who delivered at term. Consistent with these findings, measurements of species richness , late preterm , and early preterm  delivery.Using hierarchical clustering analysis (HCA) of normalized genera taxonomy read counts, vaginal swab samples were classified into three categories; normal (>90% L. crispatus), II (L. gasseri), III (L. iners), IV (diverse species), and V (L. jensenii) , followed by CST III, , CST II ; CST V , and CST IV  was most abundant among Caucasian women (P = 0.008), while Black women had greater numbers of CST III   dominance  compared to those women with a CL >25 mm : I (ii) Fig. . The mos+0 weeks) compared those delivering late preterm (34+0 to 36+6 weeks) or at term (>37+0 weeks)  compared to late preterm (31%) and term . In contrast, L. crispatus dominance associated with subsequent term birth  and L. iners positively associated with delivery <34 weeks  Fig. , Table 2L. crispatus dominance (CST I) were Caucasian , but this was not significant. In those women delivering <34 with L. iners dominance (CST III), similar proportions were represented across ethnic groups . A total of 67 pregnant women were eligible and consented to recruitment, of which 25 were found to have a short CL <25 mm and received progesterone until 34 weeks of gestation. The remaining 42 women did not experience cervical shortening or receive any subsequent preventative intervention, and hence were used as controls. Demographics of the two groups were comparable although, as per study design, the mean CL at commencement of progesterone was significantly lower in the “short CL” than the “normal” control group  at comparable screening gestations . A total of 234 high vaginal samples were collected from longitudinal follow-up  at matched gestational ages among groups -dominated microbiome was associated with high stability throughout pregnancy with 92% (24/26) of women maintaining L. crispatus dominance across all sampling time points. In contrast, significantly lower stability was observed in the 23 women exhibiting a L. iners-dominated microbiome at the first sampling with 17 (74%) of these women experiencing a shift to an alternative CST at some stage during their pregnancy (P < 0.0001). Similar levels of CST-shifting were observed in those women receiving vaginal supplementation  and control patients  (P = 0.3).The dynamics of individual vaginal CSTs during pregnancy were then longitudinally assessed in both progesterone and control cohorts Fig. . RegardlL. gasseri, or any other species in the control compared to progesterone cohorts  of women who subsequently delivered <34 weeks of gestation compared to 24% (5/21) in women delivering >34 weeks. At delivery, L. iners dominance was observed in 50% (2/4) at 22 weeks and 100% (4/4) at 28 weeks  whereas bacterial dysbiosis is positively associated with preterm delivery (odds ratio 2.3) [Lactobacillus species  [L. crispatus is advantageous and associated with term delivery whereas L. iners is associated with increased risk of preterm delivery. Furthermore, L. iners is associated more specifically with a risk of early (<34 weeks) rather than late (34–37 weeks) preterm birth. High relative abundance of L. crispatus is highly specific for term birth, with a false positive rate (1 specificity) of just 3% in our population of women at high risk because of a previous preterm birth. In this population, second trimester dominance of L. iners carries a 67% detection rate  for preterm birth before 34 weeks; a screening sensitivity comparable to cervical length, the current and primary screening tool used for preterm birth surveillance [L. iners dominance in vaginal swab samples collected from 13 preterm births derived from a low-risk cohort of 111 pregnancies, and none of whom delivered before 33 weeks of gestation [Lactobacillus species and could not identify other pathobionts in the samples.A healthy vaginal microbiome in non-gravid and gravid subjects is often described as being synonymous with low bacterial diversity and ominance –66. Exam1.2–4.8) . Using ceillance , 68. Conestation . HoweverLactobacillus species and risk of subsequent preterm birth, our data indicate that Lactobacillus spp. depletion or vaginal dysbiosis in the second trimester does not appear to contribute to preterm birth risk. The role of early gestational vaginal dysbiosis in the pathology of preterm birth is controversial. In agreement with our findings, a recent longitudinal analysis of the vaginal microbiome by Romero and colleagues in 18 women experiencing preterm birth (<34 weeks gestation) reported no association between preterm birth and vaginal microbial dysbiosis when compared to controls experiencing term delivery (n = 72) [n = 15), which vaginal bacterial diversity does correlate with risk of preterm delivery [+3/7 days).While our study reveals a clear relationship between relative abundance of vaginal (n = 72) . However(n = 72) , 24. In (n = 72)  reporteddelivery . The cliOur presented data provide some suggestion that vaginal microbiota in Black women may not play as an important contributory role to preterm birth pathogenesis as Caucasians and Asians. We did not however have sufficient power to demonstrate the significance of this, but this may be worth examining in future studies.L. iners-dominated microbiome in the second trimester compared to women with an L. crispatus-dominated microbiome. L. iners has been reported as an intermediary between lactobacilli dominance and CST IV-associated states and is the predominant microbiome in peri-menopausal women as they transition through to postmenopausal dominance of anaerobic bacteria [L. iners and the maternal host likely provides a vaginal mucosal environment permissible to colonization by BV-associated pathogens, a setting in which it tolerates co-existence well [Lactobacillus species, L. iners also induces secretion of pro-inflammatory cytokines when human vaginal epithelial cells are observed in vitro, whereas L. crispatus does not [In our study, we also observed a high rate of CST-shifting in women with an bacteria . Interacnce well , 70. Unldoes not , 72.L. iners that promotes risk of early preterm birth, but because an L. iners-dominated vaginal microbiome has less stability, there is a tendency for transition to BV-associated CST-IV [L. iners is the prominent vaginal species following antibiotic treatment for BV [Lactobacillus species and concluded that it was BV rather than species of Lactobacillus that conferred the risk.Other evidence for a role of bacterial dysbiosis in the pathology of preterm birth includes the long recognized association between bacterial vaginosis (BV) and increased risk of preterm birth; however, evidence suggests that screening and treating BV in pregnancy reduces preterm delivery in certain cohorts , but notd CST-IV , 75. Indt for BV . Older sLactobacillus species in the context of reproductive health have revealed major species-specific differences in the capacity to prevent pathobiont colonization and viral infections [Lactobacillus spp. produce both the d- and l-lactic acid isomers [L. iners, an increased ratio of l to d-lactic acid has previously been shown to promote expression of vaginal extracellular matrix metalloproteinase inducer (EMMPRIN) and the activation of matrix metalloproteinase-8 (MMP8), which may subsequently modulate cervical integrity [L. crispatus, which instead preferentially excretes high levels of d-lactic acid and greater overall levels of lactic acid than L. iners [d-lactic acid are associated with L. crispatus dominance and enhanced trapping of HIV-1 virions in cervico-vaginal mucosa whereas low concentrations of d-lactic acid associated with L. iners dominance permits comparatively rapid diffusion of virions through cervico-vaginal mucosa [L. iners dominance of vaginal microbial communities during pregnancy may lead to the modulation of local tissue inflammation and remodeling pathways and to disruption of chemical and mechanical mucosal barriers protective against ascending infection and increase the risk of preterm birth. Such mechanisms may account for the observed association between L. iners dominance and a short cervical length (<25 mm) seen in our study at 16 weeks of gestation, which itself is highly specific for preterm birth [Recent investigations into the protective role of fections , 77, 78  isomers , the chintegrity . ConversL. iners . Apart frm birth .L. iners in the vagina during pregnancy, we postulated that any associated poor pregnancy outcomes might be attenuated by the anti-inflammatory actions of progesterone [Considering the potential pro-inflammatory roles played by esterone , 82. Hown = 34/161). The mean gestation at birth of 32+6 weeks within our preterm birth cohort, and a distribution of gestational ages ranging from 24 to 36 weeks, enabled the characterization of microbial profiles associated with both early (<34 weeks) and late (34 > 37 weeks) preterm birth, providing a broader observational base for microbial-host interactions in pregnancy. The primary limitation was the small number of women receiving progesterone (n = 25) and the lack of an equivalent control group with a short CL <25 mm not receiving any intervention or receiving a placebo. A short CL significantly increases subsequent preterm birth risk [A particular strength of our study is that we characterized the vaginal microbiome in a comparatively large patient cohort at high risk of preterm birth. This strength was demonstrated by a high spontaneous preterm birth rate (rth risk ; therefoLactobacillus species have differing associations with outcome in pregnancies at high risk of preterm birth. Detection of vaginal microbial composition in the early second trimester may be used to stratify preterm birth risk; L. crispatus dominance is highly predictive of term birth, while high L. iners relative abundance is associated with increased risk of preterm birth and warrants heighted surveillance. Increased diversity of vaginal microbiota at 16 weeks of gestation is not associated with increased risk of preterm birth. The use of progesterone therapy for preterm birth prevention does not appear to adversely affect the relative abundance of vaginal Lactobacillus species or species diversity, indicating that progesterone’s mode of action during pregnancy is likely not via modulation of vaginal microbial communities. Patients and clinicians who may be concerned about the “infection risk” associated with the use of vaginal pessaries during high-risk pregnancy can be reassured.Our data indicate that specific


Hydatid cyst is an endemic disease frequently localized to the liver. It is frequently observed in Southeast Europe, Middle East, and Turkey. Although the cyst rupture can occur spontaneously, it can also occur upon albendazole treatment. Its surgical treatment includes cystotomy, capitonnage, and wedge resection. A 56-year-old male immigrant was admitted with fever, pain, and cough. Albendazole treatment was initiated and elective surgery was planned. Upon his admission to emergency service, he was diagnosed with pneumonia, and a spontaneous cyst rupture was detected. Thoracotomy and cystotomy were performed. Bile leakage aspiration and lung wedge resection were also performed. Different surgical methods are used in the treatment of hydatid cysts depending on the localization and complications. Follow-up with antihelminthic drugs such as albendazole and mebendazole is recommended in medical treatment. Echinococcus granulosus which is most frequently seen in the liver, followed by the lungs [Hydatid cyst is a parasitic disease caused byhe lungs , 2. It ihe lungs , 4.Cyst hydatid may remain symptomless for years but also may show pressure symptoms due to the growth, rupture to the neighboring structures, or becoming contaminated with infection. In our case, the hepatic cyst hydatid, which did not cause anaphylaxis despite being ruptured, was treated.3 and C-reactive protein (CRP) 232 mg/dL tomography showed echinococcosis cyst (CE) 102 × 92 mm at the liver segments 6-7. Abdominal ultrasonography revealed a CE-4 type cystic lesion of 106 × 70 mm at the right lobe  13.000/mm Figures . He was  Figures . Cystoto leakage . RepeateHydatid cyst rupture can be spontaneous, iatrogenic, or traumatic. Rupture of hydatid cyst in diaphragmatic location is rare. Coughing, dyspnea, fever, hemoptysis, flank pain, chest pain, and secondary pneumonia with pressure to the neighboring bronchi can develop due to the pulmonary rupture of the hydatid cyst on the diaphragmatic surface of the liver .Bronchopneumonia, similar to our case, can develop due to hydatid cyst of the lung, or it can be asymptomatic. While secondary infections develop due to the rupture of the cyst (in 5–8% of the cases), if the cyst fluid enters to the blood circulation of the host, anaphylaxis and allergic reactions can occur –8.Primary lung hydatid cysts can be asymptomatic, as well as spontaneously ruptured or infected. Treatment options include surgical draining of the cyst, peeling of the germinative membrane, and, for inoperable patients, albendazole treatment . SpontanIn our case, capitonnage was not performed, since the cyst was close to diaphragmatic surface, and bile leakage was observed during follow-up. Later, wedge resection was performed in the lung, due to the localization of the cyst. Hydatid cyst in the liver was attached to the diaphragmatic surface and cystotomy was performed. Bile accumulation in the liver pouch occurred, as omentopexy was not performed. Bilious content was aspirated and the area was washed with saline. Albendazole treatment (800 mgr/day) was continued for three months.Spontaneous ruptures can occur due to trauma or increase in the pressure of the growing cyst . Upon itIn conclusion, a ruptured hydatid cyst may present asymptomatically or with an anaphylactic reaction. In symptomatic cases, depending on the organ where the cyst is located, surgical excision and capitonnage can be performed. Primary lesion at the dome of the liver can be ruptured into the lung through the diaphragmatic route. In such cases, wedge resection and cystotomy to the primary region are performed, and recurrences are followed with albendazole treatment.