Effectiveness of antibacterial prophylaxis during induction chemotherapy in children with acute lymphoblastic leukemia.

BACKGROUND: Pediatric patients receiving induction chemotherapy for newly diagnosed acute lymphoblastic leukemia (ALL) are at high risk of developing life-threatening infections. We investigated whether uniform antibacterial guidelines, including mandatory antibacterial prophylaxis in afebrile patients during induction, decreases the incidence of microbiologically documented bacteremia. METHODS: Between 2012 and 2015, 230 patients with newly diagnosed ALL (aged 1-21) were enrolled on Dana-Farber Cancer Institute ALL Consortium Protocol 11-001 (DFCI 11-001). Induction therapy, regardless of risk group, included vincristine, prednisone, doxorubicin, methotrexate, and PEG-asparaginase. Afebrile patients received fluoroquinolone prophylaxis at the initiation of induction and those presenting with fever received broad-spectrum antibiotics; antibiotics were continued until blood count recovery. Rates of documented bacteremias and fungal infections on DFCI 11-001 were compared to those on the predecessor protocol (DFCI 05-001), which included the same induction phase without antibiotic prophylaxis guidelines. RESULTS: Sixty-six (28.7%) patients received fluoroquinolone prophylaxis, the remaining patients received broad-spectrum antibiotics. Twenty-four (36.4%) patients on prophylaxis developed fever and seven (10.6%) developed bacteremia. The overall rate of infection during induction on DFCI 11-001 was lower than on DFCl 05-001 (14.3% vs. 26.3%, P < 0.0001) due to a decreased rate of bacteremia (10.9% vs. 24.4%, P < 0.0001). The rate of fungal infections (4.8% vs. 3.6%) and induction death (0.9% vs. 2%) was not significantly different. CONCLUSION: For children with newly diagnosed ALL, uniform antibiotic administration until blood count recovery, including fluoroquinolone prophylaxis for afebrile patients, reduced the incidence of bacteremia during the induction phase. Larger, randomized studies should be performed to confirm these findings.

Does interference with mucoperiosteum and palatal bone affect craniofacial growth? An experimental study in beagles.

This study was designed to assess the effects of raising mucoperiosteal flaps and exposing palatal bone at the time of palatoplasty. Using 62 beagle puppies as subjects, we tested the hypothesis that raising mucoperiosteal flaps does not interfere with craniofacial growth. We further hypothesized that the size of the area of bone exposed following palatoplasty does affect subsequent craniofacial growth. The animals were divided into four groups: two control groups (unoperated and unrepaired) and two experimental groups. In the first experimental group, two-flap palatoplasty was used to close the surgically induced palatal defect, leaving narrow strips (0 to 2.5 mm) of bone exposed lateral to the flaps. In the second group, one flap was raised to close the defect, leaving a wide area (5 to 6 mm) of palatal bone exposed on one side. Thirty-four direct craniometric measurements were analyzed. Animals that had elevation of both mucoperiosteal flaps with narrow strips of denuded bone on both sides had less severe craniofacial growth aberrations than those in which the defect was left unrepaired or was repaired with one mucoperiosteal flap leaving a wider area of bare bone exposed. These findings suggest that raising mucoperiosteal flaps is less detrimental to craniofacial growth than leaving large areas of exposed palatal bone.

The effects of lip repair with and without soft-tissue undermining and delayed palate repair on maxillary growth: an experimental study in beagles.

Undermining of the soft tissue on the surface of the maxilla at the time of cleft lip repair remains a controversial issue in cleft management. Using 64 eight-week-old beagles, we tested the hypothesis that lip repair with soft-tissue undermining contributes more to maxillofacial growth aberrations than lip repair without these additional procedures. Animals were assigned to four groups: unoperated controls, unrepaired controls, and two experimental groups (with and without undermining). Defects simulating cleft of the lip, alveolus, and palate were surgically created in the unrepaired and experimental animals. At 36 weeks of age, 11 measurements were made directly on the cleaned maxillae. Analysis revealed that all groups with surgically created defects were significantly different from normal; however, animals with undermining exhibited the greatest group deviation from normal. These findings reaffirm our earlier conclusions that undermining of the soft tissue on the surface of the maxilla is detrimental to maxillofacial growth.

Simultaneous cleft lip and palate repair: an experimental study in beagles.

This study was designed to test the hypothesis that simultaneous lip and palate repair results in more severe craniofacial growth aberrations than lip repair or palate repair performed separately. Seventy-six purebred beagles were divided into five groups. Two of these groups were controls (unoperated and unrepaired animals); the three remaining groups were experimental (in one group only the lip was repaired, in another only the palate was repaired, and in the last the lip and palate were repaired simultaneously). Cephalometric measurements were analyzed using univariate and multivariate statistical techniques. In multivariate analysis, stepwise multiple regression and discrimination were applied to precisely assess the effects of the various surgical procedures. The results of this study indicate that simultaneous lip and palate repair results in more severe craniofacial growth aberrations than lip repair or palate repair performed separately.

A comparative study of facial growth following lip and palate repair performed in sequence and simultaneously: an experimental study in beagles.

This study was designed to assess the effects of the commonly accepted sequence of cleft lip and palate repair on subsequent maxillofacial growth and to compare these effects with those resulting from simultaneous lip and palate repair. Using 62 eight-week-old normal beagles, we tested the hypothesis that sequential repair (lip first, palate second) of surgically induced lip and palate defects is less detrimental to maxillofacial growth than simultaneous repair of both surgically created defects. Animals were assigned to one of four groups: two control groups (unoperated and unrepaired) and two experimental groups. Defects simulating cleft of the lip, alveolus, and palate were surgically created in the unrepaired controls and in the experimental animals. In one experimental group, the lip and palate defects were repaired immediately and simultaneously. In the other experimental group--simulating current clinical practice--the lip defect was repaired first at the time that it was created, while closure of the palatal defect was delayed 4 weeks. After the animals were killed at 36 weeks of age, 11 maxillary variables were measured directly from cleaned skulls and analyzed by using univariate and multivariate techniques. Animals that had lip and palate defects closed in sequence had less severe maxillofacial aberrations than animals with simultaneously closed defects. Sequential closure of the defects also had identifiable effects on maxillofacial form. The growth aberrations observed among animals with sequential closure, however, are primarily attributable to surgical creation of the defects and not to the surgical repair. Delaying palate repair is less traumatic to the subsequent growth of the maxillary complex than simultaneous repair of lip and palate defects.

Relationship between the sequence of lip and palate repair and maxillary growth: an experimental study in beagles.

The present study was designed to evaluate the relationship between varying sequences of lip and palate repair and maxillary growth. To investigate this problem, an experimental study using beagles was conducted to assess the influence of three different sequences of lip and palate repair. The first sequence constitutes the commonly accepted approach of lip repair first, palate repair second. The second sequence was reversed: palate repair first, lip repair second. The third sequence consisted of simultaneous lip and palate repair. Using 70 eight-week-old beagles, we tested the following hypothesis: The sequence of lip repair first and palate repair second is less detrimental to maxillary growth than the other two sequences. The animals were assigned to two control groups (unoperated and unrepaired animals) and three experimental groups, in which three different sequences of repair were executed. Upon sacrifice, 11 maxillary variables were measured directly from cleaned skulls and analyzed by univariate and multivariate techniques. The most important finding from this analysis is that the commonly accepted sequence of cleft lip and palate repair (lip first, palate second) is less detrimental to maxillary growth than repairing the palate first and the lip second or simultaneous closure of both defects.

Multidisciplinary treatment results for patients with isolated cleft palate.

Fifty-eight patients with cleft palate only who had received treatment in the Department of Otolaryngology-Head and Neck Surgery at the University of Iowa were examined for treatment results. Forty-one (70.7 percent) of the 58 patients showed a syndrome or suggestive factors. An unusually high percentage (36 percent) of the 58 patients required secondary surgery for velopharyngeal dysfunction or showed indications for surgery at examination. Some but not all of the relatively low success rate appears related to surgical experience. Speech proficiency, hearing acuity, and dental status were within normal limits or nearly so. The 20 patients with pharyngeal flap surgery were doing well, with minimal indications of functional obstruction.

Results of multidisciplinary management of bilateral cleft lip and palate at the Iowa Cleft Palate Center.

Bilateral cleft of the lip and palate is by many standards the most complex and severe form of the defect. The complexity and severity of the defect require an unusual degree of cooperation among all specialists and especially between the surgeon and the orthodontist. There are no published findings that we know about in which comprehensive data from a number of disciplines are reported for the same group of bilateral cleft patients. Fifty randomly selected patients with bilateral complete clefts were examined by the Iowa team and two orthodontists from other institutions. The evaluations revealed that a large number of patients over the age of 10 have multiple residual problems requiring further treatment. Only 23 percent of the older patients studied were judged to have had treatment completed by the surgeon, speech pathologist, and orthodontist. It is very difficult to state whether the results obtained by our team can be considered satisfactory because there are no comparable studies that have attempted to evaluate the same parameters in multidisciplinary management.

Role of animal models in experimental studies of craniofacial growth following cleft lip and palate repair.

The present study was designed to examine the role of the animal model on investigations of craniofacial growth. Identical experimental protocols were followed using 6-week-old rabbits and 8-week-old beagles. Three groups were used for each species, two control groups and one experimental group. The groups within each experimental model were compared for lip pressure, occlusion, and cephalometrics. Statistical analyses including analyses of correlations were used to evaluate dimensional craniofacial relations. The results of this study revealed that dimensional relations were significantly different in rabbits and beagles despite the similarities observed in overall craniofacial growth aberrations. Analysis of the results does not allow strong conclusions about which animal model (rabbits or beagles) is more appropriate for studying craniofacial growth.

Periosteum in regeneration of palatal defects.

The influence of the periosteum on the regeneration of palatal bone was investigated in this study. Eighty, 8-week-old, purebred beagle dogs were assigned randomly to four groups: (1) unoperated dogs as a group control; dogs in which the mid-third of the palate was surgically removed and (2) left unrepaired (unrepaired controls); (3) repaired with mucosal flaps; (4) repaired with mucoperiosteal flaps. Five animals from each group were killed at 4, 6, 8, and 12 weeks after surgery and coronal sections examined under light microscopy. Among the animals with complete soft tissue healing, 8 of 12 dogs from Group 2, 11 of 20 from Group 3, and 10 of 19 from Group 4 showed complete bone regeneration. No significant differences were found overall in bone thickness and bone density measurements between Group 3 and Group 4. Histologically, a well-differentiated periosteum was present on the maxilla at 4 weeks, even in animals in which the periosteum had not been preserved in the original flap. These results suggest that maintaining the periosteum at surgical closure does not influence bone regeneration in beagles up to 12 weeks of age. We suggest that osteoprogenitor cells, migrating from the undisturbed local periosteum adjacent to the defect, were responsible for the new bone growth in our study.