Risk Assessment of Sleep Disordered Breathing in Cleft Lip and/or Palate.

OBJECTIVE: Children with cleft lip and/or palate (CL/P) are at increased risk for Sleep Disordered Breathing (SDB), particularly Obstructive Sleep Apnea (OSA). At our institution, routine screening for SDB is performed using the Chevrin Pediatric Sleep Questionnaire (PSQ). This analysis is a practice audit looking at the outcomes of screening children with CL/P. DESIGN/SETTING/PATIENTS/PARTICIPANTS: A single-center, retrospective analysis was done of all non-syndromic patients with CL/P over the age of 36 months over a 4-year period. Children with known OSA were eliminated from analysis. MAIN OUTCOME MEASURES: Univariate logistic regression was used to assess predictors for SDB (PSQ score > 8) amongst various patient, disease, and treatment characteristics. Outcomes of those screened were tracked. RESULTS: Of the 239 patients in the study cohort, 43 (18%) had positive PSQs. These subjects were more likely to have class III dental occlusion with maxillary retrusion (OR = 2.65, 95% CI: 1.2-5.8, p = 0.02). There were no differences amongst age, type of cleft, Veau classification, BMI, or history of pharyngeal surgery. One third of the group did not complete recommended testing. Twenty-five subjects with positive sleep screening underwent subsequent polysomnography and 21 (84%) had OSA. CONCLUSION: Routine screening reveals a significant proportion of patients with CL/P with symptoms suggestive of OSA. While several patients did not complete confirmatory testing, those who completed a PSG had a high rate of identification of OSA. After excluding children with known OSA, patients with SDB are also likely to have class III dental occlusion and maxillary retrusion.

Assessment of Gender Disparities and Geographic Variations in Payments from Industry among Plastic Surgeons in the United States.

BACKGROUND: Various medical specialties have demonstrated gender disparities involving industry-supported payments. The authors sought to determine whether such disparities exist within plastic surgery. METHODS: Industry contributions to plastic surgeons practicing in the United States were extracted from the Centers for Medicare and Medicaid Services Open Payments 2013 to 2017 databases. Specialists' gender was obtained through online searches. Kruskal-Wallis tests compared payments (in U.S. dollars) by gender (overall and by payment category). Linear regression estimated the independent association of female gender with increased/reduced payments while controlling for state-level variations. RESULTS: Of 1518 plastic surgeons, 13.4 percent were female. Of $44.4 million total payments from the industry, $3.35 million were made to female plastic surgeons (p < 0.01). During the study period, female plastic surgeons received lower overall payments than male plastic surgeons [median, $3500 (interquartile range, $800 to $9500) versus $4160.60 (interquartile range, $1000 to $19,728.20); p < 0.01]. This trend persisted nationwide after normalizing for year [$2562.50/year (interquartile range, $770 to $5916.25/year) versus $3200/year (interquartile range, $955 to $8715.15/year); p = 0.02] and at the state level in all 38 states where there was female representation. Analysis of payment categories revealed that honoraria payments were significantly higher for male plastic surgeons [$4738 (interquartile range, $1648 to $16,100) versus $1750 (interquartile range, $750 to $4100); p = 0.02]. Within risk-adjusted analysis, female plastic surgeons received $3473.21/year (95 percent CI, $671.61 to $6274.81; p = 0.02) less than male plastic surgeons. CONCLUSIONS: Gender disparities involving industry payments exist in plastic surgery at both national and state levels. Factors contributing to this phenomenon must be explored to understand implications of this gap.

Effects of radiation and chemotherapy on adipose stem cells: Implications for use in fat grafting in cancer patients.

Autologous fat transplantation is a versatile tool in reconstructive surgery. Adipose-derived stem cells (ASCs) increase survival of fat grafts and thus are increasingly used for breast reconstruction in breast cancer patients. However, radiation and/or chemotherapy have been proposed to inhibit soft tissue regeneration in wound healing thus suggesting alteration in stem cell pathways. Therefore, elucidating effects of radiation and chemotherapy on ASCs is critical if one desires to enhance the survival of fat grafts in patients. This review outlines our work evaluating the function and recoverability of ASCs from radiation or chemotherapy patients, focusing specifically on their availability as a source of autologous stem cells for fat grafting and breast reconstruction in cancer patients. Even though evidence suggests radiation and chemotherapy negatively influence ASCs at the cellular level, the efficiency of the isolation and differentiation capacity did not appear influenced in patients after receiving chemotherapy treatment, although fat from radiated patients exhibited significantly altered ASC differentiation into endothelial-like cells. Further, the in vitro growth rates of patient's ASCs do not differ significantly before or after treatment. Taken together, these studies suggest ASCs as an important new tool for grafting and reconstruction even when radiation and chemotherapy treatment are involved.

Change in Initial Tympanostomy Tube Placement Timing Yields Decreased Burden of Care Without Increased Complications in Patients With Cleft Lip and Palate.

OBJECTIVE: To report a practice audit of the consequences of a change in protocol in the timing of placement of tympanostomy tubes in infants with cleft lip and palate. PARTICIPANTS: All children with a diagnosis of cleft lip and palate, treated between November 1998 and May 2006 under the old protocol, and between December 2012 and July 2016 under a new protocol. Under the old protocol, tympanostomy tubes were first inserted at the time of lip repair at around age 2 months. Under the new protocol, tympanostomy tubes were deferred until the time of palate repair around the age of 9 months. Children with syndromic diagnoses other than Stickler syndrome and Van der Woude syndrome, and children who failed newborn hearing screen were excluded. MAIN OUTCOME MEASURES: Incidence of otorrhea from birth to 6 months after palate repair and presence of hearing loss at ages 1 and 2. RESULTS: Deferral of tympanostomy tubes until the time of palate repair decreases the burden of care due to otorrhea as compared to early tympanostomy tubes at the time of lip repair. There was no significant difference in the incidence of hearing thresholds at or below 15 dB at age 1 or 2. CONCLUSIONS: Placement of tympanostomy tubes at the time of palate repair balances the goals of minimizing the adverse effects from middle ear effusion and minimizing the burden of care on our patients and their families.

Isolation and identification of adipose-derived stromal/stem cells from breast cancer patients after exposure neoadjuvant chemotherapy.

BACKGROUND: With recent research advances, adipose-derived stromal/stem cells (ASCs) have been demonstrated to facilitate the survival of fat grafts and thus are increasingly used for reconstructive procedures following surgery for breast cancer. Unfortunately, in patients, following radiation and chemotherapy for breast cancer suggest that these cancer treatment therapies may limit stem cell cellular functions important for soft tissue wound healing. For clinical translation to patients that have undergone cancer treatment, it is necessary to understand the effects of these therapies on the ASC's ability to improve fat graft survival in clinical practice. AIM: To investigate whether the impact on ASCs function capacity and recovery in cancer patients may be due to the chemotherapy. METHODS: ASCs were isolated from the cancerous side and noncancerous side of the breast from the same patients with receiving neoadjuvant chemotherapy (NAC) or not-receiving NAC. ASCs were in vitro treated with 5-fluorouracil (5-FU), doxorubicin (DXR), and cyclophosphamide (Cytoxan) at various concentrations. The stem cells yield, cell viability, and proliferation rates were measured by growth curves and MTT assays. Differentiation capacity for adipogenesis was determined by qPCR analysis of the specific gene markers and histological staining. RESULTS: No significant differences were observed between the yield of ASCs in patients receiving NAC treatment and not-receiving NAC. ASCs yield from the cancerous side of the breast showed lower than the noncancerous side of the breast in both patients receiving NAC and not-receiving NAC. The proliferation rates of ASCs from patients didn't differ much before and after NAC upon in vitro culture, and these cells appeared to retain the capacity to acquire adipocyte traits simile to the ASCs from patients not-receiving NAC. After cessation and washout of the drugs for another a week of culturing, ASCs showed a slow recovery of cell growth capacity in 5-FU-treated groups but was not observed in ASCs treated with DXR groups. CONCLUSION: Neoadjuvant therapies do not affect the functioning capacity of ASCs. ASCs may hold great potential to serve as a cell source for fat grafting and reconstruction in patients undergoing chemotherapy.

Histone Deacetylase Inhibitors Enhance Cytotoxicity Towards Breast Tumors While Preserving the Wound-Healing Function of Adipose-Derived Stem Cells.

INTRODUCTION: Paclitaxel improves the oncologic response of breast cancer resections; however, it may negatively affect the wound-healing potential of human adipose-derived stem cells (hASCs) for fat grafting and reconstructive surgery. Histone deacetylase inhibitors (HDACis) modify the epigenetic regulation of gene expression and stabilize microtubules similarly to paclitaxel, thus, creating a synergistic mechanism of cell cycle arrest. We aim to combine these drugs to enhance cytotoxicity towards breast cancer cells, while preserving the wound-healing function of hASCs for downstream reconstructive applications. METHODS: Triple negative breast cancer cells (MBA-MB-231) and hASCs (institutional review board-approved clinical isolates) were treated with a standard therapeutic dose of paclitaxel (1.0 µM) or with low-dose paclitaxel (0.1 µM) combined with the HDACi suberoylanilide hydroxamic acid or trichostatin A. Cell viability, gene expression, apoptosis, and wound-healing/migration were measured via methylthiazol tetrazolium assay, quantitative real-time polymerase chain reaction, annexin V assay, and fibroblast scratch assay, respectively. RESULTS: Combined HDACi and low-dose paclitaxel therapy maintained cytotoxicity towards breast cancer cells and preserved adipose-derived stem cell viability. Histone deacetylase inhibitor demonstrated selective anti-inflammatory effects on adipose-derived stem cell gene expression and decreased expression of the proapoptotic gene FAS. Furthermore, HDACi therapy did not increase relative apoptosis within hASCs. A scratch assay demonstrated enhanced wound healing among injured fibroblasts indirectly co-cultured with HDACi-treated hASCs. CONCLUSIONS: Combining HDACi with low-dose paclitaxel improved cytotoxicity towards breast cancer cells and preserved hASC viability. Furthermore, enhanced wound healing was observed by improved migration in a fibroblast scratch assay. These results suggest that the addition of HDACi to taxane chemotherapy regimens may improve oncologic results and wound-healing outcomes after reconstructive surgery.

Koenen tumors in tuberous sclerosis: a review and clinical considerations for treatment.

Koenen tumors, or periungual and subungual fibromas, are a benign, cutaneous manifestation of tuberous sclerosis. They are disfiguring, painful, and challenging to treat as they frequently recur. Various laser and chemical ablation techniques have been described with variable long-term results and there is limited published literature to suggest a standard treatment. Through a review of the available literature and a successful experience with a patient with lower extremity Koenen tumor, we present treatment considerations for managing these troublesome tumors.

Operative Nd:YAG laser plus postoperative hyperbaric oxygen reduces surgical morbidity after radical head and neck cancer surgery and complex reconstruction.

UNLABELLED: Complications after radical head and neck cancer surgery in irradiated patients are frequent and life-threatening. Hemorrhage, salivary fistulas, wound infections that expose the carotid sheath, among others, make these patients difficult management challenges in the ICU. We studied the effects of Nd:YAG laser surgery plus hyperbaric oxygen (HBO2) therapy on radical head and neck resections and complex reconstruction as a means of reducing postoperative morbidity and mortality. METHODS: 43 head and neck cancer patients were reviewed. Eight (STD) had standard surgery; 35 (YAG:HBO2) had Nd:YAG laser and postoperative HBO2. RESULTS: Age, staging, primary tumor site, sex, reconstruction procedure and transfusion did not differ between STD and YAG/HBO2. All STD and Nd:YAG/HBO2 patients were irradiated, median dosages 5,000 centi-Gray (cGy) and 7,000 cGy, respectively (p = 0.073). Median blood loss was 1,000 ml STD and 700 ml YAG/HBO2 (p = 0.046). There were no postoperative deaths. Major surgical site complications developed in 63% of the STD and 17% of the YAG/HBO2 patients (p = 0.017). All STD and 62% of YAG/HBO2 cancers recurred within 28 months of surgery (p = 0.152). Within the STD and YAG/HBO2 groups, 100% and 77% of deaths, respectively, were due to cancer. CONCLUSIONS: Combined Nd:YAG laser surgery and HBO2 reduces morbidity in radical head and neck cancer surgery. Recurrent disease and poor cancer survival remain common in this high-risk population.

The safety of pelvic surgery in the morbidly obese with and without combined panniculectomy: a comparison of results.

PURPOSE: The purpose of our study was to evaluate the benefit of panniculectomy combined with pelvic surgery in the morbidly obese patient. Previous literature has found this combined procedure in this particular patient population to have increased morbidity and that it was not beneficial. METHODS: A chart review was performed an all patients who underwent pelvic surgery with or without a panniculectomy between June 2004 and June 2005. Only morbidly obese patients (body mass index of >40 kg/m2) were included in the study. Factors evaluated were operative times, intraoperative blood loss, weight of pannus resection specimen, length of hospital stay, wound infection rate, and other complications. All data were analyzed using Levene test for equality of variances and the t test for the equality of means. RESULTS: Thirty-six patients had combined panniculectomy and abdominal hysterectomy, 14 had an abdominal hysterectomy without a panniculectomy. The mean operative times for the combined procedure was 3.4 hours versus 2.6 hours without panniculectomy. The mean estimated blood loss was 526 mL for the combined procedure (CP) and 536 mL for hysterectomy alone (HA). There were 2 wound infections in the CP group (5.6%) versus 3 in the HA group (21.4%). There was one wound dehiscence in the CP group (2.8%) and one in the HA group (7.1%). There was one inadvertent enterotomy in the HA group (7.1%) and none in the CP group. There were no statistical differences noted for any variable including patient body mass index, mean operative time, estimated blood loss, or rate of complications. CONCLUSIONS: Our findings, in contrast to previous findings, reveal that panniculectomy combined with pelvic surgery in the morbidly obese is a safe procedure that can decrease the incidence of intraoperative complications and postoperative wound complications without significantly increasing operative time or blood loss.

Pulse doppler and M-mode to assess viability of cardiac allografts using heterotopic femoral heart transplantation in rats.

Noninvasive assessment of heterotopic heart transplants using Doppler echocardiography was first described in two patients by Allen at Stanford in 1981. Since then, numerous experiments studying heterotopic heart transplantation in humans and large animals have confirmed its utility by employing either an intra-abdominal or cervical model. In rats, however, prior research investigating intra-abdominal heterotopic hearts has showed echocardiography to be ineffective. We have recently developed a new technique for heterotopic femoral heart transplantation in rats, which employs the novel use of trans-femoral echocardiography. Therefore, our goal was to re-examine the efficacy of echocardiography for detection of graft rejection.

Review of vascularized bone marrow transplantation: current status and future clinical applications.

In this review, we examine the applicability of the vascularized bone marrow transplant (VBMT) as an alternative to conventional bone marrow transplantation (BMT). As a new surgical approach, the VBMT is unique by transplantation of the stromal environment that eliminates the need for an engraftment period, provides critical signaling and modulatory functions, and may potentiate tolerance induction. Thus far, VBMT studies have demonstrated an absence of graft-versus-host disease (GVHD) and robust engraftment into nonmanipulated as well as irradiated recipients with evidence of immunological tolerance. Further investigation is needed to determine the applicability of VBMT as an alternative to BMT.

A new modified technique for heterotopic femoral heart transplantation in rats.

BACKGROUND: Abbott developed the first experimental accessory heart transplant rat model in 1964. This intra-abdominal model required a labor-intensive aortic anastomosis. In 1971, Heron modified the operation by using sutureless cervical vessel anastomoses. Rao and Lisitza developed a femoral heart accessory transplant model in 1985. Our goal was to improve this femoral model for the study of cardiac transplantation between both syngeneic and allogeneic rats. METHODS: ACI and Lewis rats weighing 150 to 350 g were used as donors and recipients (n = 12). The left common carotid and left pulmonary arteries were anastomosed to the femoral artery and vein in an end-to-end fashion, respectively. Improved modifications included the use of hemostatic vessel clips, heparinization of both donor and recipient, a ventricular prolene stay-suture for secure graft placement, and transfemoral echocardiography (TFE). Total operative time averaged 61 +/- 12 minutes. RESULTS: Femoral accessory transplanted hearts (FATHs) allowed easier pulse palpation and access for TFE versus previously described cervical and intra-abdominal models. This modification allows precise detection of acute graft rejection (AGR) and is defined as absent ventricular contraction in the presence of anastomostic patency. CONCLUSIONS: Our new modified technique for heterotopic femoral heart transplantation in rats is a relatively easily learned and reproduced procedure that allows superior allograft access for palpation and improved echocardiographic assessment. Femoral heterotopic heart transplantation remains an effective model for allograft transplantation study.

Effects of varying the monetary value of voucher-based incentives on abstinence achieved during and following treatment among cocaine-dependent outpatients.

AIMS: This study examined whether increasing the amount of abstinence achieved during outpatient treatment for cocaine dependence is an effective method for increasing longer-term cocaine abstinence. DESIGN: A two-condition, parallel groups, randomized controlled trial was conducted. SETTING: The trial was conducted in a university-based research clinic. PARTICIPANTS: A total of 100 cocaine-dependent outpatients participated in the trial. INTERVENTION: Participants were assigned randomly to receive treatment based on the community reinforcement approach (CRA) plus voucher-based incentives set at a relatively high monetary value (maximal value = $1995/12 weeks) or CRA with vouchers set at a relatively low monetary value (maximal value = $499/12 weeks). Vouchers were earned contingent on cocaine-negative urinalysis results during the initial 12 weeks of the 24-week outpatient treatment. MEASUREMENTS: Outcomes were evaluated using urine-toxicology testing, questionnaires and other self-report instruments. FINDINGS: Increasing voucher value increased the duration of continuous cocaine abstinence achieved during the 24-week treatment period. Point-prevalence cocaine abstinence assessed every 3 months throughout an 18-month follow-up period was greater in the high- than low-value voucher conditions. The duration of abstinence achieved during treatment predicted abstinence during follow-up, although that relationship weakened over time. CONCLUSIONS: Increasing the value of abstinence-contingent incentives during the initial weeks of treatment appears to represent an effective method for increasing during-treatment and longer-term cocaine abstinence, but the positive association of during-treatment abstinence with longer-term outcome dissipates with time.

From experimental rat hindlimb to clinical face composite tissue allotransplantation: historical background and current status.

The purpose of this article is to review the historical background and clinical status of composite tissue allotransplantation and to discuss the scientific evolution of clinical face transplantation. Composite tissue allotransplantation (CTA) rapidly progressed in the 1980s with the discovery of cyclosporine. Although the most success has been achieved with hand transplantation, others have made progress with allografts of trachea, peripheral nerve, flexor tendon apparatus, vascularized knee, larynx, abdominal wall, and most recently, partial face. The world's first partial face allotransplantation occurred in November 2005 in France. In April of 2006, there was a second performed in China. As of today, there are now multiple institutions with plans to attempt the world's first full facial/scalp transplant. Complete facial/scalp allotransplantation offers a viable alternative for unfortunate individuals suffering severe facial disfigurement and is a product of many decades of experimental research, beginning with rat hindlimb allografts.

Absence of graft-versus-host disease in the isolated vascularized bone marrow transplant.

An isolated vascularized bone marrow transplant (iVBMT) model was developed to study the contribution of the bone marrow component in a composite tissue allograft. We hypothesized that the iVBMT would be functional and cause graft-versus-host disease (GVHD) in a fraction of the recipients. Lewis iVBMT grafts were transplanted to Lewis-Brown Norway recipients. Animals were sacrificed at various times from 1 to 14 weeks. Polymerase chain reaction for microchimerism was performed on the host's marrow. No animals exhibited signs of GVHD at death. Histologic examination of the grafts showed a normal mix of hematopoietic and fatty elements and appeared to be functional. Tissues usually affected-tongue, ear, liver, and gut-also showed no evidence of disease. Polymerase chain reaction demonstrated microchimerism in both groups. These findings suggest that the vascularized bone marrow within a composite tissue allograft is not the component that causes GVHD; rather, it may serve an immunomodulatory function for tolerance induction.

An extraperitoneal isolated vascularized bone marrow transplant model in the rat.

An isolated vascularized bone marrow transplant (iVBMT) model was previously developed in the rat to specifically study the role of bone marrow and its environment in a composite tissue allotransplant. An extraperitoneal model was successfully created to avoid laparotomy and cross-clamping of the great vessels. The extraperitoneal iVBMT model consisted of a left donor femur that was harvested with its nutrient vessels, anastomosed to the right femoral vessels in a syngeneic host, and then placed subcutaneously in the abdominal wall. At explant, the graft vessels were grossly patent, and histology of the graft bones showed a viable marrow compartment. Polymerase chain reaction demonstrated peripheral chimerism in the recipients. This model is technically simple with minimal morbidity in the recipient animals. By using the iVBMT, future studies across semiallogeneic and allogeneic barriers will help define the role of the bone marrow compartment in composite tissue allotransplants to potentially induce immune tolerance.

Beyond easy answers: the plastic surgeon and prenatal diagnosis.

OBJECTIVE: To explore how plastic surgeons handle the issue of prenatal diagnosis of cleft lip and palate. DESIGN: Mail survey. PARTICIPANTS: The plastic surgeon listed as team contact in the team directory of the American Cleft Palate-Craniofacial Association was identified. In cases in which a plastic surgeon was not listed as a team contact, the first plastic surgeon listed as a team member was identified. A total of 211 surgeons were contacted. INTERVENTION: Each surgeon was mailed a survey asking for his/her experience in prenatal diagnosis for cleft conditions. Ethical issues concerning the surgeon's personal beliefs about abortion and the potential influence of the surgeon's presentation of information were explored. RESULTS: A 50% response rate was obtained. Eighty-five percent of respondents were experienced in prenatal counseling; 92% offer consults on a routine basis. Ninety-six percent indicated they did so because they felt it was helpful to families. Treatment (98%), appearance of clefts (96%), cleft etiology (94%), and associated problems (40%) were discussed most commonly. Termination was rarely discussed (5%). Of those who had not met with a family, 82% said they had never been asked to do so. Most respondents felt families sought consultation for information and rarely sought consultation to decide on abortion. The majority felt their personal beliefs about abortion did not influence their willingness to meet with parents. The majority of surgeons in both groups felt it was ethical to give an opinion on pregnancy termination if asked (55% of experienced surgeons, 44% of inexperienced surgeons); however, a significantly larger number of the surgeons who had not met with a family were unsure of their opinion. CONCLUSIONS: Prenatal counseling of parents of a fetus with cleft lip/palate is common among plastic surgeons. There is uniformity in the information discussed. There is no agreement among surgeons about the ethical issues of pregnancy termination and the surgeon's role in that discussion.