Endoscopic closure of gastrointestinal perforations and fistulas using the Ovesco Over-The-Scope Clip system at a tertiary care hospital center. / Cierre endoscópico de perforaciones y fístulas del tracto digestivo mediante el sistema «Over-the scope clip¼ (Ovesco), en un centro terciario.

INTRODUCTION AND AIM: Enteric perforations and fistulas are difficult to manage due to comorbidities, poor nutritional status, and anatomic challenges related to multiple interventions in those patients. The use of endoscopic methods as a nonsurgical approach is increasing. The aim of the present study was to describe the clinical experience with the use of the Ovesco Over-The-Scope Clip system in the closure of perforations, fistulas, and other indications in the digestive tract at a tertiary care hospital center. MATERIALS AND METHODS: A case series was carried out on patients that underwent lesion closure with the Ovesco clip, within the time frame of January 2015 to December 2017. RESULTS: The Ovesco clip was used for closure in 14 patients ranging in age from 21-90 years, with different indications: iatrogenic perforations; anastomotic leaks and fistulas; tracheoesophageal fistulas; and esophagogastric perforation. Technical success was achieved in 100% of the patients and clinical success in 78.57%. No complications were reported. CONCLUSIONS: The Ovesco Over-The-Scope Clip system is a safe and effective method for managing gastrointestinal acute perforations and fistulas.

Risk factors associated with post-hemorrhagic hydrocephalus among very low birth weight infants of 24-28 weeks gestation.

OBJECTIVE: Post-hemorrhagic hydrocephalus (PHH) is associated with morbidity and mortality among very low birth weight (VLBW) infants. This study aimed to determine risk factors for PHH among VLBW infants with peri-intraventricular hemorrhage (PIVH). STUDY DESIGN: This is a population-based cohort of VLBW infants of 24 to 28 weeks gestation, born in Israel from 1995 to 2012. Infants in whom a brain ultrasound was not performed before 28 days or with major congenital malformations were excluded. Univariate and multivariable analyses identified risk factors associated with PHH. RESULTS: The final study cohort comprised 2811 infants with grade 2 or higher PIVH, of whom 610 (21.7%) developed PHH. PHH was independently associated with PIVH severity, with bilateral grade 3 PIVH and PIVH grade 3 and contralateral grade 4 having the highest risks (odds ratio (OR) 12.2, 95% confidence interval (CI) 8.56 to 17.4 and OR 13.7, 95% CI 9.4 to 20.1, respectively). Unilateral grade 3 or 4 PIVH's had moderately increased risks of PHH (OR 3.50, 95% CI 2.26 to 5.42 and OR 3.79, 95% CI 2.35 to 6.12, respectively). PHH was independently associated with increasing gestational age (GA) and with neonatal morbidities including patent ductus arteriosus (OR 1.47, 95% CI 1.15 to 1.88 if medically treated and OR 3.01, 95% CI 2.11 to 4.29 if surgically treated), sepsis (OR 1.79, 95% CI 1.44 to 2.22) and necrotizing enterocolitis (OR 1.60, 95% CI 1.18 to 2.17). CONCLUSIONS: Among VLBW infants with PIVH, PHH was independently associated with PIVH severity group, increasing GA and acute neonatal morbidities. Unilateral grade 3 or 4 PIVH was associated with a moderate risk of developing PHH compared with bilateral severe hemorrhages.

Macrosomic newborns of non-diabetic mothers: anthropometric measurements and neonatal complications.

OBJECTIVE: To assess the association of anthropometric measurements with neonatal complications in macrosomic newborns of non-diabetic mothers. DESIGN: Retrospective cohort study. PATIENTS: All liveborn, singleton, full term newborns with birth weight ≥4000 g born to non-diabetic mothers at a tertiary medical centre in 1995-2005 (n=2766, study group) were matched to the next born, healthy, full term infant with a birth weight of 3000-4000 g (control group). Exclusion criteria were multiple birth, congenital infection, major malformations and pregnancy complications. INTERVENTION: Data collection by file review. OUTCOME MEASURES: Complication rates were compared between study and control groups and between symmetric and asymmetric macrosomic newborns, defined by weight/length ratio (WLR), Body Mass Index and Ponderal Index. RESULTS: The 2766 non-diabetic macrosomic infants identified were matched to 2766 control infants. The macrosomic group had higher rates of hypoglycaemia (1.2% vs 0.5%, p=0.008), transient tachypnoea of the newborn (1.5% vs 0.5%, p<0.001), hyperthermia (0.6% vs 0.1%, p=0.012), and birth trauma (2% vs 0.7%, p<0.001), with no cases of symptomatic polycythaemia, and only one case of hypoglycaemia. Hypoglycaemia was positively associated with birth weight. It was significantly higher in the asymmetric than the symmetric macrosomic newborns, defined by WLR (1.7% vs 0.3%, p<0.001). CONCLUSIONS: Macrosomic infants of non-diabetic mothers are at increased risk of neonatal complications. However, routine measurements of haematocrit and calcium may not be necessary. Symmetric macrosomic infants (by WLR) have a similar rate of hypoglycaemia as normal-weight infants. Thus, repeat glucose measurements in symmetric macrosomic infants are not justified.

The matrilin-3 VWA1 domain modulates interleukin-6 release from primary human chondrocytes.

OBJECTIVE: We previously demonstrated the ability of matrilin-3 to modulate the gene expression profile of primary human chondrocytes (PHCs) toward a state favoring cartilage catabolism. The structure within matrilin-3 responsible for the induction of these catabolic genes is unknown. Here, we investigated the potential of matrilin-3 (MATN3) and truncated matrilin-3 proteins, in both monomeric and oligomeric form, to stimulate interleukin (IL)-6 release in PHCs. METHODS: We expressed full-length matrilin-3 oligomers, matrilin-3 von Willebrand factor A (VWA) domain oligomers, matrilin-3 four epidermal growth factor (EGF) domain oligomers, matrilin-3 monomers without oligomerization domains, matrilin-3 VWA domain monomers, and matrilin-3 4EGF monomers. We then incubated PHCs in the absence or presence of full-length matrilin-3 or one of the truncated matrilin-3 proteins and finally determined the release of IL-6 in cell-culture supernatants. RESULTS: The addition of full-length matrilin-3 oligomers, matrilin-3 VWA domain oligomers, and, less pronounced, matrilin-3 monomers without oligomerization domains, and matrilin-3 4EGF-oligomers to the cell-culture medium led to a significant induction of IL-6 in PHCs. DISCUSSION: Based on recombinant expression of different matrilin-3 domains in both monomeric and oligomeric form, this work demonstrated that the VWA1 domain of matrilin-3 is primarily responsible for the induction of IL-6 release and that the oligomerization of the VWA1 domain markedly promotes its activity.

Long-term outcome following selective serotonin reuptake inhibitor induced neonatal abstinence syndrome.

OBJECTIVE: To assess the long-term neurodevelopment of children exposed in utero to selective serotonin reuptake inhibitors (SSRIs) that developed a neonatal abstinence syndrome (NAS). STUDY DESIGN: Neurodevelopmental evaluation was performed at the age of 2 to 6 years. Children who developed NAS were compared with those who did not using univariate and logistic regression analyses. RESULT: Thirty children with NAS and 52 without NAS participated in the study. Both groups were similar in mean cognitive ability (106.9±14.0 vs 100.5±14.6, P=0.12) and developmental scores (98.9±11.4 vs 95.7±9.9, P=0.21). However, there was a trend towards small head circumference in the NAS group (20 vs 6%, P=0.068). NAS was associated with an increased risk of social-behavior abnormalities (odds ratio (OR) 3.03, 95% confidence interval (CI) 1.07 to 8.60, P=0.04) and advanced maternal age (OR 1.12, 95% CI 1.00 to 1.25, P=0.04). CONCLUSION: Infants who developed NAS had normal cognitive ability, but were at an increased risk for social-behavioral abnormalities. Follow-up evaluation of symptomatic neonates should be considered.

Mortality of full-term infants during the first month of life in a tertiary care hospital.

OBJECTIVE: The neonatal mortality rate is disproportionately influenced by preterm infants and does not reflect the rate in full-term infants. Our objectives were to estimate the full-term neonatal mortality rate and to identify causes of death in full-term infants during the first month of life. STUDY DESIGN: A retrospective study of full-term infant deaths during a 6-year period from 2000 to 2005, in a tertiary medical center. RESULT: During the study period there were 44,703 full-term births and 31 deaths, representing a mortality rate of 0.69 per 1,000 live births. The main cause of death was congenital anomalies (64.5%), specifically cardiac anomalies. Other causes were chromosomal anomalies or syndromes (12.9%), labor complications (12.9%), infections (3.2%), congenital diseases (3.2%) and metabolic disorders (3.2%). CONCLUSION: The mortality rate of full-term infants may be lower than previous estimates. Efforts aimed at decreasing mortality among full-term infants should focus on prenatal diagnosis.

Bronchopulmonary dysplasia in very low birth weight infants is associated with prolonged hospital stay.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is associated with prolonged hospital length of stay (LOS) and delayed discharge home. OBJECTIVES: To evaluate the association between BPD and LOS and to assess the contribution of concomitant major morbidities on LOS among infants with BPD. STUDY DESIGN: A population-based observational study of very low birth weight (VLBW) infants born from 1995 through 2003. Multivariate analyses, adjusted for perinatal variables, assessed the association between BPD and concomitant morbidities on LOS. RESULTS: Of 10 134 survivors, 1926 (19.0%) had BPD. The adjusted LOS for infants with and without BPD was 84.1 days (95% CI, 82.8, 85.6) and 58.1 days (95% CI, 57.2, 59.0), respectively. Addition of a single concomitant morbidity increased mean LOS by 4 to 13 days. CONCLUSIONS: BPD is a major cause of increased length of hospitalization among VLBW infants. Preventive or therapeutic modalities are required to reduce the significant burden of this condition.

Effect of smoking on crevicular polymorphonuclear neutrophil function in periodontally healthy subjects.

BACKGROUND: Polymorphonuclear neutrophils (PMNs) represent the first line of cellular defences in the gingival crevice. Smoking, as probably the most important environmental risk factor for periodontitis, has been shown to adversely affect many neutrophil functions. OBJECTIVE: The aim of this study was to investigate the influence of smoking on PMN numbers and function in periodontally healthy smokers and non-smokers. METHODS: Sixty subjects were recruited: 15 non-smokers, 15 light smokers (< 5 cigarettes/day), 15 moderate smokers (5-15 cigarettes/day) and 15 heavy smokers (> 15 cigarettes/day). Full mouth plaque index, sulcus bleeding index and probing depths were measured. Crevicular washings were obtained from all subjects to harvest PMNs. Numbers of PMNs, percentage viability, and percentage phagocytosis of opsonized Candida albicans were recorded. RESULTS: Mean plaque scores and probing depths were (non-significantly) increased in smokers compared to non-smokers. Mean sulcus bleeding index scores were significantly lower in moderate (0.10 +/- 0.10) and heavy (0.07 +/- 0.11) smokers compared to non-smokers (0.14 +/- 0.13) (p < 0.05). Compared to non-smokers (1.73 +/- 1.08 x 10(6)/ml), the numbers of PMNs were higher in light (1.98 +/- 0.96 x 10(6)/ml) and moderate (2.03 +/- 1.43 x 10(6)/ml) smokers and were lower in heavy smokers (1.68 +/- 1.18 x 10(6)/ml), though there were no significant differences in PMN counts between the groups (p > 0.05). Percentage viability of PMNs was significantly lower in light (77.6 +/- 7.8%), moderate (76.5 +/- 8.2%) and heavy (75.0 +/- 6.5%) smokers compared to non-smokers (85.5 +/- 6.0%) (p < 0.05). Furthermore, the ability of PMNs to phagocytose was significantly impaired in light (58.3 +/- 4.1%), moderate (51.9 +/- 2.33%) and heavy (40.9 +/- 3.5%) smokers compared to non-smokers (74.1 +/- 4.1%) (p < 0.05), with evidence of a dose-response effect. CONCLUSION: Cigarette smoking adversely affected PMN viability and function in this periodontally healthy population.

Do hyperoxaemia and hypocapnia add to the risk of brain injury after intrapartum asphyxia?

BACKGROUND: Episodes of hyperoxaemia and hypocapnia, which may contribute to brain injury, occur unintentionally in severely asphyxiated neonates in the first postnatal hours. OBJECTIVE: To determine whether hyperoxaemia and/or hypocapnia during the first 2 hours of life add to the risk of brain injury after intrapartum asphyxia. METHODS: Retrospective cohort study in term infants with post-asphyxial hypoxic ischaemic encephalopathy (HIE) born between 1985 and 1995. Severe and moderate hyperoxaemia were defined as Pao(2) >26.6 and Pao(2) >13.3 kPa (200 and 100 mm Hg). Severe and moderate hypocapnia were defined as Paco(2) <2.6 and Paco(2) <3.3 kPa (20 and 25 mm Hg). Adverse outcome ascertained by age 24 months was defined as death, severe cerebral palsy, or any cerebral palsy with blindness, deafness, or developmental delay. With outcome as the dependent variable, multivariate analyses were performed including hyperoxaemic and hypocapnic variables, and factors adjusted for initial disease severity. RESULTS: Of 244 infants, 218 had known outcomes, 127 of which were adverse (64 deaths, 63 neurodevelopmental deficits). Multivariate analyses showed an association between adverse outcome and episodes of severe hyperoxaemia (odds ratio (OR) 3.85, 95% confidence interval (CI) 1.67 to 8.88, p = 0.002), and severe hypocapnia (OR 2.34, 95% CI 1.02 to 5.37, p = 0.044). The risk of adverse outcome was highest in infants who had both severe hyperoxaemia and severe hypocapnia (OR 4.56, 95% CI 1.4 to 14.9, p = 0.012). CONCLUSIONS: Severe hyperoxaemia and severe hypocapnia were associated with adverse outcome in infants with post-asphyxial HIE. During the first hours of life, oxygen supplementation and ventilation should be rigorously controlled.

Risk factors associated with candidaemia in the neonatal intensive care unit: a case-control study.

The incidence of candidaemia is steadily increasing in neonatal intensive care units (NICUs). Several neonatal risk factors for candidaemia have been identified, however, the number of cases in controlled studies is small and knowledge concerning maternal and perinatal risk factors is limited. The present study attempted to identify modifiable, independent maternal, perinatal and neonatal risk factors for candidaemia using a retrospective case-control study in the NICU of a tertiary-care paediatric medical centre. The study group consisted of 56 neonates admitted to the NICU between 1996 and 2000 who acquired candidaemia. The control group comprised the first infant admitted immediately after each study infant matched for gestational age (+/-10 days) and birthweight (+/-200 g). Potential maternal, perinatal and neonatal risk factors were compared between the groups using statistical methods and analysed by univariate and multivariate stepwise logistic regression models. The independent risk factors found to be significantly associated with increased risk of candidaemia were duration of ventilation and presence of bacteraemia before candidaemia. Maternal steroids had a significant protective effect. The positive predictive value using these three parameters was 78.38%. Maximizing in-utero steroid treatment in high-risk pregnancies, minimizing the days of mechanical ventilation and investment of efforts in prevention of bacteraemia may help to reduce the incidence of candidaemia in the NICU.

Disinfection with 10% povidone-iodine versus 0.5% chlorhexidine gluconate in 70% isopropanol in the neonatal intensive care unit.

AIM: The finding that 10% povidone-iodine skin disinfectant may compromise thyroid function in premature infants prompted its replacement with 0.5% chlorhexidine gluconate solution in 70% isopropanol. The objective of this study was to compare the incidence rates of true infection and contamination associated with the use of these two disinfectants in the neonatal intensive care unit. METHODS: The study population comprised two cohorts of infants admitted to our neonatal intensive care unit: 1) in 1992-1993 when only 10% povidone-iodine was used as a skin disinfectant, and 2) in 1995-1996 when only 0.5% chlorhexidine gluconate solution in 70% isopropanol was used. A retrospective chart review was conducted to determine whether all documented positive blood, CSF and suprapubic aspirate cultures indicated true infection or contamination. True infection was defined as clinical symptoms and/or laboratory abnormalities suggestive of sepsis, with positive blood, CSF or suprapubic aspirate cultures. RESULTS: 1146 infants were admitted during the study periods, 507 during the first period and 639 during the second. In the early group, 17.6% of infants had major malformations, 72.0% were premature and 25.2% had weights of < 1500 g. Corresponding percentages for the latter group were 16.0%, 80.6% and 32.9%, respectively. No statistically significant differences were found between the two research periods in rate of infants with positive blood cultures, true infections, or contamination. CONCLUSION: The use of 0.5% chlorhexidine gluconate solution in 70% isopropanol as a skin disinfectant is justified in neonatal intensive care units because it is not associated with an increased incidence of infections as opposed to 10% povidone-iodine and is devoid of detrimental effects.

Ocular toxicity and antenatal exposure to chloroquine or hydroxychloroquine for rheumatic diseases.

Chronic use of chloroquine and hydroxychloroquine inthe treatment of rheumatic disease carries a small risk of sight-threatening pigmentary retinopathy. To obtain safety data for its use in pregnancy, we did ophthalmic examinations in 21 children born to women who took these drugsduring pregnancy. Average daily maternal doses of the two drugs were 317 mg hydroxychloroquine and 332 mg chloroquine. The mean duration of gestational exposure was 7.2 months. No ophthalmic abnormality was detected in these children. Therapeutic use of these drugs during pregnancy may not pose a significant risk of ocular toxicity to offspring.

Non-protein bound dienogest in serum and salivary dienogest in women taking the oral contraceptives Certostat and Valette.

Dienogest (17 alpha-cyanomethyl-17-hydroxy-4,9-estradien-3-one) is the progestagen component of the oral contraceptives Certostat and Valette. In contrast to other 19-norsteroid progestagens like levonorgestrel, norethisterone, gestodene and 3-ketodesogestrel, dienogest does not bind to sexual hormone binding globulin (SHBG). The absent binding to SHBG results in a high portion of free, non-protein bound dienogest in serum. In female volunteers taking the oral contraceptives Certostat and Trisiston, the part of non-protein bound dienogest and levonorgestrel, respectively, in serum was determined by the method of centrifugal ultrafiltration. The portion of free dienogest was found to be 9.55 +/- 0.95% (m +/- SD, n = 13) of total serum dienogest. Free levonorgestrel constituted 0.97 +/- 0.14% (n = 12) of total serum levonorgestrel. In an investigation with 47 female volunteers taking Certostat, serum total dienogest was quantified by a specific radioimmunoassay and free dienogest in serum by centrifugal ultrafiltration. In the serum samples with dienogest concentrations in the range of 4.1-57.7 ng/ml, the part of free, non-protein bound dienogest was found to be 8.90 +/- 0.54% of serum total dienogest. There is a high correlation between serum total dienogest and free dienogest (r = 0.989). In another investigation with 20 female volunteers taking the contraceptive Valette, serum total dienogest and salivary dienogest were quantified by radioimmunoassay and free dienogest in serum by centrifugal ultrafiltration. In the serum samples with dienogest concentrations in the range of 7.5-50.6 ng/ml, the part of free, non-protein bound dienogest was 8.78 +/- 0.77% of serum total dienogest. Salivary dienogest constituted 7.99 +/- 0.94% of serum total dienogest showing a high correlation with serum free dienogest (r = 0.953) and serum total dienogest (r = 0.958). The high portion of non-protein bound compound in serum is a characteristic pharmacokinetic feature of dienogest.

A 2-step non-surgical procedure and systemic antibiotics in the treatment of rapidly progressive periodontitis.

BACKGROUND: In the last few years knowledge about periodontal infections has increased enormously, nevertheless practitioners are still seeking guidelines for suitable treatment concepts. METHODS: The aim of this study was to examine the effect of doxycycline, metronidazole, and clindamycin used adjunctively in a 2-step nonsurgical procedure in patients with rapidly progressive periodontitis (RPP). The first step included scaling, root planing, and polishing (SRP) in each quadrant using 4 to 5 visits. The second step included full-mouth enhanced root planing (RP) and wound dressing in 1 or 2 visits after SRP and the beginning of antibiotic therapy. Forty-eight patients (mean age 32.4 years) with generalized RPP, with an average of 16 sites with probing depths (PD) deeper than 8 mm, and high counts of Porphyromonas gingivalis were randomly assigned to 4 different groups: group 1 (doxycycline) n = 12, group 2 (metronidazole) n = 15, group 3 (clindamycin) n = 11, and group 4 (control group; no antibiotic treatment) n = 10. Clinical evaluations, including plaque index (PI), sulcus bleeding index (SBI), probing depth (PD), clinical attachment level (CAL), and bacteriological and crevicular cell sampling, were done at baseline (BL), 3 weeks after SRP, and 6 and 24 months after RP. RESULTS: After the first step (SRP), we observed an improvement of PI and SBI in all 4 groups, but did not see any statistically significant PD reduction 3 weeks after SRP compared to baseline. However, 6 and 24 months after the second step (RP) we observed a significantly greater reduction of PD in groups 2 and 3 and a significantly greater CAL gain in comparison to groups 1 and 4. After 24 months, the attachment level gain in group 1 and group 4 was less than 1.5 mm, and less than 1.0 mm in PD site categories 6 to 9 mm and >9 mm. PI showed no significant difference between the groups throughout the period after SRP until 24 months, compared to 3 weeks after SRP. SBI decreased most in the metronidazole and clindamycin groups. P. gingivalis and Actinobacillus actinomycetemcomitans were almost completely eradicated in these 2 groups 24 months after RP. In addition, the phagocytotic capacity of crevicular polymorphonuclear neutrophils was increased in groups 2 and 3 after the second step. CONCLUSIONS: The present results show that metronidazole and clindamycin are effective antibiotics when used adjunctively in a 2-step nonsurgical procedure of scaling and root planing in RPP patients.

Prognostic value of EEG in neonatal bacterial meningitis.

The contribution of electroencephalogram (EEG) findings early in the course of neonatal bacterial meningitis to the prediction of severe adverse outcome was assessed in a retrospective cohort study. Infants had known outcomes to 1 year of age and an EEG performed during the first week of illness. EEGs were subclassified as follows: overall EEG description, background activity, presence of positive rolandic sharp waves, presence of seizure activity, and presence of focal abnormal activity. EEG patterns predictive of severe adverse outcome were identified by univariate and multivariate analyses. Of 101 infants admitted with bacterial meningitis, 37 had an EEG performed. Of the 37 infants, 21 had adverse outcomes; nine infants died, and 12 infants had moderate or severe disability. EEG background activity and overall EEG description were identified as predictors of adverse outcome; multivariate analysis indicated that the latter was a stronger predictor (sensitivity 88%, specificity 90%). Infants with normal or mildly abnormal EEGs had good outcomes whereas those with moderate to markedly abnormal EEGs died or survived with adverse outcome. The accuracy of predictions increased when EEGs were repeated. In a high-risk population of infants with bacterial meningitis, moderate-to-markedly abnormal EEG reliably predicts adverse outcome.