Systematic review and meta-analysis of the pre-operative application of botulinum toxin for ventral hernia repair.

PURPOSE: Surgical repair of large hernia defects requires detailed pre-operative planning, particularly in cases with loss of domain. This situation often hampers mid-line reconstruction, even after component separation, when the size of the hernia is disproportional to the volume of the abdominal area. In this case, other strategies may be needed to place the viscera back into the abdominal cavity after reducing the hernia sac. The administration of botulinum toxin prior to the surgical procedure has been indicated as an adjunct for more complex cases. This results in stretching of the lateral musculature of the abdomen, allowing midline approximation. In addition, the application of botulinum toxin alone has been investigated as a means of downstaging in the management of ventral hernias, thereby precluding component separation and enabling primary closure of the midline by placement of mesh within the retromuscular space using the Rives Stoppa technique. METHODS: Systematic review of the literature for observational studies involving patients undergoing pre-operative application of botulinum toxin for ventral hernia repair was conducted according to the PRISMA guidelines. RESULTS: Advance of the lateral musculature of the abdomen by an average of 4.11 cm with low heterogeneity, as well as low rates of surgical site infection (SSI), surgical site occurrences (SSO) and recurrence, was shown. CONCLUSION: Pre-operative application of botulinum toxin for ventral hernia repair promoted an increase in the length of the lateral musculature of the abdomen which can help improve the outcomes of morbidity and recurrence.

Effect of passive smoking on thyroid function in infants.

OBJECTIVE: To evaluate the effect of passive smoking on thyroid function in infants. DESIGN AND METHODS: Cord serum tri-iodiothyronine (T3), free T3 (fT3), thyroxine (T4), free T4 (fT4), TSH, thyroxine binding globulin (TBG), thyroglobulin (TG) and cord plasma thiocyanate were measured at birth, and serum TG and thiocyanate after 1 year of life, in 18 infants born from parents who did not smoke (group A), in 18 infants with a father who smoked (group B) and in 18 infants with parents both being smokers (group C). RESULTS: No significant differences were observed in cord serum concentrations of T3, fT3, T4, fT4, TSH and TBG among the three groups. Median (range) TG concentrations (ng/ml) were 30.2 (5.0-102.0), 56.3 (20.5-208.0) and 76.0 (26.0-199.0) at birth (P=0.009 for groups A and B compared; P=0.0002 for groups A and C compared), and 14.9 (5.4-32.0), 19.5 (10.0-57.5) and 20.0 (14.0-40.7) at 1 year (P=0.017 for groups A and C compared), in the three groups respectively, and thiocyanate concentrations (mmol/l) were 3.3 (0.0-51.4), 12.9 (0.0-122.2) and 27.8 (3.3-184.5) at birth (P=0.015 for groups A and C compared), and 3.1 (0.0-32.7), 6.0 (0.0-47.3) and 20.3 (0.0-230.8) at 1 year (P=0.01 for groups A and C compared) in the three groups respectively. CONCLUSIONS: TG and thiocyanate concentrations at birth and at 1 year of age in infants of smoking parents are greater than in infants with non-smoking parents. These results indicate that the change in thyroid function as evaluated by serum TG concentrations observed at birth can persist at least for 1 year if the exposure to passive smoking from both parents is continued. Increased TG concentrations may be due to a direct effect of thiocyanate on the thyroid gland.

Transplantation of cord blood progenitor cells can promote bone resorption in autosomal recessive osteopetrosis.

Allogeneic BMT has been reported to be the only curative therapy for children with juvenile autosomal recessive osteopetrosis. We report the case of a 14-month-old child in whom bone resorption was observed after cord blood transplantation (CBT). The patient was given CBT from an unrelated newborn matched for five of six HLA antigens. At the time of transplantation, the child presented with neurological symptoms, with feeding problems and visual impairment. A successful engraftment of donor hematopoiesis was demonstrated and the child experienced grade I acute GVHD. Progressive bone clearing was achieved and a bone marrow trephine demonstrated signs of osteoclast function. Despite full engraftment and bone resorption, neurologic deterioration did not improve. This experience documents that CBT can promote the correction of juvenile osteopetrosis. The shorter time needed both to identify an unrelated donor and to perform the transplant, as well as the lower incidence of GVHD make this procedure more appealing than BMT in children lacking an HLA-compatible relative.

Hematopoietic and immune recovery after transplantation of cord blood progenitor cells in children.

Matched related cord blood transplantation (CBT) has been successfully used to rescue patients undergoing myeloablative therapy. However, few data are available on the kinetics of hematological and immunological reconstitution of CBT recipients. We have investigated the hematological engraftment and immune recovery following related CBT in three patients, with acute lymphoblastic leukemia, aged 10, 9 and 7 years and with a body weight of 31, 40 and 25 kg, respectively. All patients engrafted and none experienced acute or chronic graft-versus-host disease. The time needed to achieve granulocyte recovery was 13, 26 and 29 days, respectively and platelet recovery occurred in 28, 49 and 51 days. All patients presented a marked increase of HbF, the values observed being much greater than those documented in patients given marrow transplantation and comparable with those observed in normal children in the first year of age. The recovery of T cell immunity, as well as that of natural killer subpopulations, mimicked that described in BMT recipients, a quicker return of CD8+ T cells determining the characteristic inversion of CD4/CD8 ratio. An impressive increase in the percentage and absolute number of B lymphocytes, apparently not related to viral infections, was demonstrable in all three cases. These data suggest that CBT recipients can experience a slight delay in hematological recovery when compared with patients given BMT. The reconstitution of erythropoiesis seems to recapitulate the ontogenetic pattern and the kinetics of recovery of the immune system reproduce that observed after BMT with the peculiarity of B cell expansion in peripheral blood.

Does the emergence and persistence of donor-derived leukaemia-reactive cytotoxic T lymphocytes protect patients given an allogeneic BMT from recurrence? Results of a preliminary study.

The frequency of CTL precursors (CTLp) directed towards recipient-derived pre-transplant leukaemic blasts (LB) was measured in the peripheral blood of nine children with acute leukaemia and given BMT from either an HLA-identical sibling or a matched unrelated donor (MUD). Patients were evaluated at various time points between 1 month and more than 2 years after transplantation. A high frequency of donor-derived LB-reactive CTLp was detectable 2-6 months after BMT in all children and persisted for at least up to 18 months in the eight patients in haematological remission, while it rapidly declined in the only patient who relapsed. Generation of LB-reactive T cell clones obtained from some of these patients demonstrates that various T lymphocyte subsets, either HLA class I-restricted/TCR-dependent or HLA-unrestricted, contribute to this phenomenon. The in vitro GVL effect here described seems to be at least partially separated from GVHR, since no correlation was observed between the emergence of LB-reactive CTLp and the development and/or severity of GVHD. Development of LB-reactive CTL in the patients was independent of the frequency of these cells in the donor. These data suggest that donor-derived CTL activity specifically directed towards leukaemic blasts may develop in patients given allogeneic BMT and contribute to the maintenance of a state of haematological remission.

Characterisation of CTL directed towards non-inherited maternal alloantigens in human cord blood.

Allogeneic cord blood transplantation (CBT), especially from unrelated donors, is being increasingly used for treating paediatric patients with both malignant and non-malignant disorders. Recent clinical and experimental evidence suggests that human cord blood mononuclear cells (CBMC) may acquire in utero a state of tolerance towards non-inherited maternal antigens (NIMA). In order to better define this phenomenon, we measured, by means of a limiting dilution assay (LDA), the frequency of NIMA-specific CTL precursors (CTLp) in cord blood samples obtained from 13 healthy neonates. The immunophenotype of the effector cells recovered from LDA was also analysed. Data concerning both CTLp frequency and phenotype of effector cells were compared with those obtained stimulating CBMC with cells of paternal origin (NIPA) and adult PBMC with allogeneic targets. Results showed that cytotoxic cells directed towards cells of maternal origin could be detected in all cord blood samples tested. Phenotype analysis demonstrated that NIPA elicit the expansion of CD3+/CD8bright T cells, a phenotype associated with alloreactive CTL. By contrast, NIMA preferentially stimulated the expansion of CD3-/CD8dim+ cells, a phenotype associated with NK cells, which are known to be able, in certain clinical conditions, to kill allogeneic haematopoietic cells without causing GVHD. Thus, our results indicate that, when evaluated in a limiting dilution condition, NIMA-reactive cord blood cells are detectable and a preferential expansion of NK cells is observed.

Bacteriological and clinical efficacy of various antibiotics used in the treatment of streptococcal pharyngitis in Italy. An epidemiological study.

A total of 123 community paediatricians and 23 microbiology laboratories studied the clinical and bacteriological efficacy of treatment of group A streptococcal pharyngitis in Italy. Of 1065 patients, from whom Streptococcus pyogenes was isolated, 723 returned to follow up and of these 138 (19%) still had a positive throat culture. The erythromycin resistance (ER) rate was 23.7% with resistance phenotype distribution of: 31.7% constitutive (CR), 26.6% inducible (IR) and 41.7% efflux pump (M) resistance phenotype. All strains were susceptible to the beta-lactam agents tested. CR strains were highly resistant to all 14, 15 and 16 membered macrolides with the exception of rokitamycin which showed activity against 37.8% of isolates. All phenotype M and some IR isolates were susceptible to clindamycin, rokitamycin, josamycin and spiramycin; clarithromycin was active against a small percentage of strains belonging to the IR and M phenotype. Bacterial eradication was found in 85.5, 78.7 and 75.8% of the penicillin, macrolide and cephalosporin treated groups. Genotyping of strains showed that 8.7% of the 19% of cases classified as 'failed bacterial eradication' were due to recolonization with a different isolate, observed exclusively among beta-lactams treated patients. Clinical cure was achieved in a high percentage of cases, irrespective of the antibiotic prescribed, with the best clinical efficacy being found following therapy with amoxycillin and clarithromycin (90.9%).

Prevalence of respiratory syncytial virus infection in Italian infants hospitalized for acute lower respiratory tract infections, and association between respiratory syncytial virus infection risk factors and disease severity.

This study was designed to collect data on the prevalence of respiratory syncytial virus (RSV) infection in Italy in infants hospitalized for lower respiratory tract infections, and to evaluate which of the recognized risk factors might be associated with disease severity. Thirty-two centers throughout Italy participated in the study. Over a 6-month period (November 1,1999 to April 30, 2000), we evaluated all children < 2 years of age hospitalized for lower respiratory tract infections. All subjects were tested for RSV within 24 hr of hospitalization by using an immuno-enzymatic diagnostic test (Abbott Testpack, RSV). Logistic regression was used to identify the factors that might be associated with more severe disease or could increase the likelihood of RSV positivity in hospitalized infants. Out of a total of 1,232 children enrolled, 40.6% were found to be RSV-positive (RSV+). The peak of the RSV epidemic occurred in February, while the lowest prevalence of RSV positivity was seen in November (P < 0.05). A high proportion of study subjects had low birth weight and low gestational age. The clinical diagnosis at hospitalization was bronchiolitis in 66.7%, pneumonia in 15.3%, and wheezy bronchitis in 18.1%. In the bronchiolitis group, a higher prevalence of RSV+ was found in patients with gestational age or= 36 weeks (P < 0.04). No differences were found in the proportion of RSV+ patients in the three gestational age subgroups with pneumonia and wheezy bronchitis (P > 0.05, each comparison). Independent of the clinical diagnosis at admission, RSV infection was associated with more severe respiratory impairment. Environmental smoke exposure was higher in subjects with bronchiolitis than in those with wheezy bronchitis (P < 0.04), and RSV+ was positively related with the birth order (P < 0.05). The presence of older siblings and birth order plays an important role in RSV infection. The collected data show that, in Italy, RSV is an important cause of lower respiratory tract infection in infants. Gestational age, birth order, birth weight, and exposure to tobacco smoke affected the prevalence and severity of RSV-related lower respiratory tract disease.

Early predictors of neurodevelopmental outcome at 12-36 months in very low-birthweight infants.

We followed-up 71 preterm survivors, 36 (50.7%) females and 35 (49.3%) males, correlating the results of neurological examinations (NE) at 40 weeks of corrected gestational age (GA) and the cerebral ultrasound (US) diagnosis with the neurodevelopmental outcome at 12-36 months of life. All 34 children with normal NE at term presented adequate neurodevelopmental outcome; these subjects have a normal US scan or a scan that is pathologic for uncomplicated hemorrhage. Of the 6 children with pathologic NE, but a normal US, 3 (50%) had a normal outcome, while 2 (34%) had mild impairments and 1 (16%) grave neurodevelopmental deficits. Of the 31 subjects with pathologic NE and US, 12 (39%) showed a normal outcome, and 6 (19%) had mild and 13 (42%) grave neurodevelopmental deficits; signs of parenchymal lesions with or without periventricular hemorrhage were particularly correlated to US. We conclude that the combination of the results of NE at 40 weeks GA and brain US are useful in early neurodevelopmental prognosis in very low-birthweight infants.

Neurodevelopmental outcome in very low birth weight infants at 24 months and 5 to 7 years of age: changing diagnosis.

We describe the long-term development of 53 very low birth weight premature infants. The children were divided into 2 groups on the basis of ultrasound scan, and classified as: group I, patients with normal ultrasound scan or with uncomplicated hemorrhage; and group II, patients with complicated hemorrhage or only parenchymal lesions. Minor and major sequelae detected at 2 years of age were compared with those observed at 5 to 7 years. Our study confirms that most severely handicapped children are identified by age 2 years. Minor sequelae are more evident at 5 to 7 years and subjects with good outcome, as expressed by a McCarthy General Cognitive Index score > 80, present a discordant cognitive profile with verbal scores higher than performance scores. Therefore, we emphasize the importance of follow-up of very low birth weight premature infants until school age and stress that neonatal ultrasound scan diagnosis of parenchymal damage represents an important diagnostic tool in terms of both short- and long-term neurodevelopmental outcome.

Increased renal echogenicity in the neonate.

We report data on newborn infants with increased renal echogenicity observed at the Division of Neonatal Intensive Care of Pavia during a five-year period. Review of 1600 abdominal ultrasonic evaluations revealed 103 newborn infants (56 females and 47 males, with birth weight from 560 to 3700 g and gestational age from 25 to 42 weeks) whose kidneys showed increased echogenicity. Three patients with infantile polycystic kidney disease, two with renal candidiasis, three with dysplastic kidney and two with renal vein thrombosis showed diffuse hyperechogenicity. Three patients with hemolytic-uremic syndrome showed cortical hyperechogenicity. Increased medullary echogenicity was observed in 90 infants with renal disease secondary to perinatal asphyxia. In 76 of these patients the evaluation of renal echogenicity and the renal function improved, while in the remaining 14 newborns the renal alteration persisted until death.

Growing skull fractures of childhood. Case report and review of 132 cases.

Authors report a case of growing skull fracture, unusual complication of linear skull fracture in infancy and childhood. A review of 132 cases reported in literature is done with an analysis of general characteristics of this lesion. The most common localization is parietal (50%); clinical presentation is represented by development of seizures (54 cases), focal neurological deficit (57 cases) or loss of consciousness (50 cases). In 50% of cases interval time between head injury and first symptom varies between 1 day and 1 year. After the first year of age the 34.4% of patients develop seizures and 59% present loss of consciousness. Among patients from 1 day to 6 months of age, 46% develop seizures, 38% focal neurological deficit and 21% loss of consciousness. Asymptomatic presentation is more common in fronto-parietal or fronto-parieto-occipital localizations. In parieto-occipital and occipital localization (30 cases), 13 patients (43.3%) have seizures, 36.7% a focal neurological deficit and 60% loss of consciousness. In parieto-temporal localization there is a higher probability of seizures (62.5%) and loss of consciousness (62.5%). The long-term follow-up and the functional recovery in patients which undergo surgery is linked to the clinical presentation and early diagnosis.

Antenatal risk factors for germinal matrix hemorrhage and intraventricular hemorrhage in preterm infants.

OBJECTIVES: This study was designed to evaluate the effect of antenatal risk factors on the occurrence of germinal matrix hemorrhage or intraventricular hemorrhage in preterm infants. STUDY DESIGN: Antenatal factors were evaluated in 302 infants delivered between 24 and 33 completed weeks gestation. Ultrasonographic screening of intracranial hemorrhage was carried out in all the infants. The association between risk factors and neonatal intracranial hemorrhage was evaluated with both univariate and multivariate models. RESULTS: In stepwise logistic regression analysis, birthweight was a better predictor of neonatal germinal matrix hemorrhage than gestational age. Conversely, gestational age better predicted intraventricular hemorrhage than did birthweight. Risk factors for neonatal germinal matrix hemorrhage and intraventricular hemorrhage were dissimilar. A history of heavy (> 10 cigarettes/day) maternal smoking on admission increased the risk of germinal matrix hemorrhage three-fold (odds ratio = 3.35; 95% C.I. 1.24-9.07). Antenatal corticosteroid use reduced the risk of intraventricular hemorrhage by 76% (odds ratio = 0.24; 95% C.I. 0.09-0.61). Among patients with spontaneous preterm delivery or premature rupture of fetal membranes, the presence of labor was a significant effect modifier of the gestational-age associated risk of germinal matrix hemorrhage-intraventricular hemorrhage. CONCLUSIONS: Risk factors for neonatal germinal matrix hemorrhage are different from those for intraventricular hemorrhage. Most antenatal factors, especially those affecting fetal maturity, could influence the progression rather than the onset of intracranial hemorrhage.

Pharmacokinetics and clinical efficacy of indomethacin in premature infants with patent ductus arteriosus.

Despite a considerable amount of investigation, controversy continues concerning the use of indomethacin in inducing the closure of patent ductus arteriosus. This controversy may be attributable to differences in dosage, route of administration, postnatal age at treatment and the variable pharmacokinetics of the drug in premature infants. The pharmacokinetics and clinical efficacy of i.v. administered indomethacin in five premature infants with PDA were evaluated. There was considerable intersubject variability in the half life of elimination (63.1 +/- 38 h). This variability was mainly due to clearance (0.0086 +/- 0.0069 l/h/kg) rather than to distribution volume variability (0.54 +/- 0.27 l/kg). A reduction of half life was observed after the second dose, probably due to a maturation process. A permanent closure of the ductus was obtained in two patients after the first dose and in two patients after the second dose. The side-effects observed in our infants were transient and no long-term complication was attributable to this drug.

Review of experience with retinopathy of prematurity from the Pavia registry (1990-1993).

In this retrospective study we analysed the prevalence of retino-pathy of prematurity (ROP) and its sequelae in a sample of premature infants with birth weight less than 1500 grams. From 1 January 1990 to 31 October 1993, we studied 160 surviving premature infants with very low birth weight (< 1.500 g) referred to the Neonatal Intensive Care Unit of the I.R.C.C.S. Policlinico San Matteo, Pavia, Italy. Thirty percent of these infants suffered from ROP, and 13.7%, with severe ROP, underwent cryotherapy. These latter had very-very low birth weight (< 1.000 g) and low gestational age (< 28 weeks). Follow-up of 69 infants at 12 months for retinal sequelae, refraction defects, bin-ocular vision and ocular motility impairments gave the following results: 1) strabismus 20.3%; 2) > 3D hyperopia 3%; 3) myopia 30.4%; 4) > 5D myopia 3.7%. The incidence of refraction and ocular motility anomalies in patients with acute ROP with spontaneous remission was similar to that of unaffected premature infants. Conversely, in the patients treated with cryotherapy the incidence of strabismus and > 5D myopia was greater than for untreated infants: 30% vs 15.4% (n.s.) and 14.7% vs 0% (p = 0.05), respectively. Cryotherapy was successful in 91.9% of cases and in 37.8% of cases the cicatricial sequelae were limited to peripheral chorioretinal scars.

Assessment of peri-neonatal mortality and morbidity risk in twin pregnancy.

A case control study on peri-neonatal mortality and morbidity rates in 154 twin pregnancies has been performed. The mortality rates along with main neonatal morbidity factors were evaluated in relation to the birth weight and gestational age. The risk of death in peri-neonatal period was 17 times greater (relative risk 17.30) (p less than .00005) in newborns weighing less than 2000 g and about 15 times (r.r. 14.53) (p less than .00005) in twins born before 34th week of gestational age with respect to the controls. The Apgar score of the 2nd twin was lower than that of the 1st, both at 1' (p less than .05) and 5' (p less than .025). The development of HMD was strongly influenced by the gestational age when less than 34th week (r.r. 15.89) (p less than .00005). No difference in incidence was found between the newborns with gestational age between 34-37 weeks and those at term. The potential implications of these findings on obstetric and neonatologic treatment of LBW and VLBW twins was discussed.

[Pharmacokinetics of ceftriaxone in the first three month of life]. / Farmacocinetica del ceftriaxone nei primi tre mesi di vita.

The purpose of the study was to define more precisely ceftriaxone kinetic variations in neonates and infants during the first three months of life. Ceftriaxone pharmacokinetics were studied in 14 newborns and infants with gestational age ranging from 31 to 42 weeks and younger than three months of postnatal age. Ceftriaxone was administered as an intravenous bolus injection over 15 min at a dose of 50 mg/Kg every 24 hours, for a period of 7 to 28 days according to the bacterial diseases. 13 patients had normal renal function and one had a chronic renal insufficiency. Plasma and urine concentrations were measured by a specific HPLC assay. The mean plasma concentration was 180.7 +/- 19.9 ug/ml (mean +/- SD) 30 min after the beginning of the infusion. After 24 h the plasma value was 29.9 +/- 10.0 ug/ml. The mean elimination half-life (t1/2) was 19.9 h, the total clearance (CL) of the drug was 0.38 ml/min/Kg and the volume of distribution (Vd) was 0.32 l/Kg. About 52% of the administered dose was excreted unchanged in urine. In the patient with renal insufficiency we observed t1/2 = 38.9 h and CL = 0.10 ml/min/Kg. Only a slight accumulation of the drug (from 180.7 +/- 19.9 ug/ml to 223 +/- 15.5 ug/ml) was observed during multiple dosing. The volume of distribution and the plasma half-life were significantly correlated (negative correlation) to the postnatal age. There was no correlation between clearance and postnatal age. No side effects were observed in newborns and infants after administration of ceftriaxone.