Low-Dose Allergen-Specific Immunotherapy Induces Tolerance in a Murine Model of Shrimp Allergy.

BACKGROUND: The efficacy and safety of allergen-specific immunotherapy (AIT) are highly dose-dependent. METHODS: We investigated the dosage effects of AIT and the underlying mechanisms in a murine model of shrimp hypersensitivity. BALB/c mice were sensitized with recombinant shrimp allergen rMet e 1 and challenged orally with a high dose of rMet e 1 to elicit an allergic response. These sensitized mice were then treated with a low (0.01 mg), medium (0.05 mg), or high dosage (0.1 mg) of rMet e 1 intraperitoneally before receiving a second oral challenge. The allergic responses and immunological changes in the gut were compared between animals receiving different dosages. RESULTS: We found that all sensitized mice that received rMet e 1 immunotherapy were desensitized, regardless of the dosage, and protected at the second oral challenge. Nevertheless, the mice in the high-dosage group experienced severe systemic reactions during the treatment phase. In contrast, regulatory T (Treg) cell-associated genes were upregulated only in the low- and medium-dosage groups, and Foxp3+ cells were more abundant in the gut lymphoid tissues than in the high-dosage group. CONCLUSIONS: Our results demonstrate that low-dosage immunotherapy favors the induction of local Foxp3+ Treg cells and the upregulation of regulatory cytokines. The safety advantages and long-term efficacy of low-dosage immunotherapy should be taken into consideration when developing immunotherapy dose schedules.

Up-regulation of microRNA-210 induces immune dysfunction via targeting FOXP3 in CD4(+) T cells of psoriasis vulgaris.

Psoriasis vulgaris (PV) is a chronic inflammatory and T cell-mediated autoimmune skin disease. An immune dysfunction that is manifested by abnormally activated T cells and defective regulatory T (Treg) cells may play an important role in the pathogenesis of PV. However, the precise mechanism of the immune dysfunction in PV patients still remains unclear. In this study, we found that miR-210 expression is increased significantly in CD4(+) T cells from patients with PV and confirmed that FOXP3 is a target gene of miR-210. We also found that overexpression of miR-210 inhibits FOXP3 expression and impairs the immunosuppressive functions of Treg cells in CD4(+) T cells from healthy controls. In contrast, inhibition of miR-210 increases FOXP3 expression and reverses the immune dysfunction in CD4(+) T cells from patients with PV. Our data demonstrates that increased miR-210 induces immune dysfunction via by FOXP3 in CD4(+) T cells from patients with PV.

Surgically assisted maxillary expansion imparts three-dimensional nasal change.

PURPOSE: The impact of surgically assisted maxillary expansion (SAME) on facial soft tissue structures has not been adequately studied using 3-dimensional (3D) objective analysis. The purpose of this study was to analyze nasolabial soft tissue after SAME using 3D photographic technology. MATERIALS AND METHODS: This was a retrospective cohort study of patients undergoing SAME in which pre- and postexpansion 3D photographs (3D VECTRA Photosystem, Canfield, Fairfield, NJ) were analyzed. Nasolabial anthropometric measurements were performed using the 3D postprocessing software (Mirror). A follow-up period of at least 6 months was required for final evaluation. Two observers verified the landmarks on each dataset before measuring. Statistical analysis involved the paired t test, the Simes correction for multiple comparisons, and repeated measures analysis of covariance (ANCOVA) to control for age, gender, and the time lag between pre- and postoperative assessments. RESULTS: Twelve patients (24 photogrammetric datasets) were included. The male-to-female ratio was 0.5 (mean age, 17.3 yr). Nasal changes after SAME showed significant increases (P < .05) in alar width (from 33.1 to 34.5 mm), sill width (from 9.2 to 9.7 mm), and columella projection (from 94.1 to 95.1 mm) after the Simes correction. ANCOVA showed a significant increase in alar base width. Distinct changes in nostril shape and dimension were found, but lacked statistical significance. CONCLUSION: Three-dimensional analysis shows widening of the alar width and alar base width after SAME. The magnitude of nasal change parallels that of expansion at the piriform aperture.

Wound healing complications with intraoperative brachytherapy for head and neck cancer: a unique form of radiation injury.

BACKGROUND: Intraoperative brachytherapy (IOBT) to the tumor bed coupled with surgery has been shown to increase survival and to improve locoregional disease control after head and neck tumor extirpation. Flap reconstruction attempts to restore patient anatomy, while also covering the radioactive implants. The purpose of this study was to better characterize the wound healing complications experienced by patients undergoing reconstruction in the setting of IOBT after tumor ablation, as well as to identify risk factors predicting complications and the need for reoperation. METHODS: A retrospective chart review of patients receiving IOBT for head and neck cancer at Yale-New Haven Hospital between 2005 and 2013 was conducted. Patient, tumor, treatment, and reconstructive details were recorded. The number and type of flap complications, as well as instances in which patients had to be taken back to the operating room, were documented. Bivariate and multivariate logistic regressions were performed to identify risk factors associated with the occurrence of 1 or more flap complications, as well as the need for reoperation. RESULTS: Ninety-three patients aged 31 to 93 years (mean, 64 ± 12 years) who underwent IOBT with flap reconstruction were included in the study. Of these, 94% had a prior history of radiation (external beam or previous IOBT). Overall, 48 (51.6%) patients experienced at least 1 flap complication, the most common of which was flap dehiscence (32% of patients). Thirty-two patients (34% of the cohort) had to be taken back to the operating room at least once for flap debridement or a revision procedure. On multivariate analysis, only the placement of mandibular hardware during flap reconstruction was significantly associated with the risk of developing any type of flap complication (odds ratio, 3.7; P = 0.009) or with subsequent return to the operating room (odds ratio, 3.9; P = 0.012). CONCLUSIONS: This study, the largest of its kind, demonstrated a very high complication rate for flaps used to cover brachytherapy implants in this patient cohort. However, many of the patient complications could be managed nonoperatively. Avoiding the use of mandibular hardware with IOBT suggests a method of reducing complications with reconstruction.

Does an elevated bony ridge along the course of the metopic suture equal metopic synostosis? Implications for management.

Metopic synostosis represents an increasingly prevalent form of nonsyndromic craniosynostosis. Premature fusion of the metopic suture classically results in trigonocephaly, hypotelorism, temporal narrowing, and a pronounced midline forehead ridge. However, as varying degrees of skull deformity exist, there is confusion regarding the appropriate management for an infant with a metopic ridge. We report on a 2-month-old infant with clinical manifestations of metopic synostosis but with a patent metopic suture documented on computed tomography scan. We examine the implications for management related to fusion of the suture, age of the patient, and severity of the head deformity.

A range of condylar hypoplasia exists in Treacher Collins syndrome.

PURPOSE: Temporomandibular joint malformation is a complex deformity in Treacher-Collins syndrome (TCS); however, it is not well characterized. This study aimed to better clarify this pathology by volumetrically assessing the mandibular condyle in patients with TCS compared with normal controls and the relative contribution of the condyle to hemimandibular volume. MATERIALS AND METHODS: A retrospective, cross-sectional analysis of pediatric patients with TCS and unaffected controls was performed. The study sample was comprised of Treacher Collins patients. The predictor variable in this study was disease status (TCS diagnosis vs control), and the outcome variable was condylar volume. Demographic information was collected, and 3-dimensional computed tomographic data were analyzed by computerized segmentation (Materialise). Volumes were obtained for TCS condyles and compared with age-matched controls using the Student t test. RESULTS: Three-dimensional computed tomographic scans were identified in 10 patients with TCS (20 sides) and 14 control subjects (28 sides). The TCS group included 4 female and 6 male patients (age, 0.3 to 213 mo; average age, 66.5 mo). The control cohort included 7 female and 7 male subjects (average age, 68.8 mo). Evaluation of the mandibular condyle showed that patients with TCS had a significantly smaller condylar volume than control patients (TCS, 178.28 ± 182.74 mm(3); control, 863.55 ± 367.20 mm(3); P < .001). Additional intragroup analysis showed no significant differences between the left and right condylar volumes in the TCS group (P = .267). In addition, the condyle for patients with TCS represented a smaller proportion of hemimandibular volume compared with controls (1.37% vs 4.19%, respectively; P < .001). CONCLUSIONS: The results of the this study suggest that condylar volumes are significantly smaller in patients with TCS compared with age-matched controls, and the condyle represents a smaller fraction of the total mandibular volume for patients with TCS than in unaffected children. In addition, there is considerable variability of condylar size in patients with TCS. These facts portend treatment decisions because a functional temporomandibular joint is necessary and may need to be reconstructed as a first stage before effective implementation of distraction procedures.

Effectiveness of Bundled Hyperpolypharmacy Deprescribing Compared With Usual Care Among Older Adults: A Randomized Clinical Trial.

Importance: Older patients using many prescription drugs (hyperpolypharmacy) may be at increased risk of adverse drug effects. Objective: To test the effectiveness and safety of a quality intervention intended to reduce hyperpolypharmacy. Design, Setting, and Participants: This randomized clinical trial allocated patients 76 years or older who used 10 or more prescription medications to a deprescribing intervention or to usual care (1:1 ratio) at an integrated health system with multiple preexisting deprescribing workflows. Data were collected from October 15, 2020, to July 29, 2022. Intervention: Physician-pharmacist collaborative drug therapy management, standard-of-care practice recommendations, shared decision-making, and deprescribing protocols administered by telephone over multiple cycles for a maximum of 180 days after allocation. Main Outcomes and Measures: Primary end points were change in the number of medications and in the prevalence of geriatric syndrome (falls, cognition, urinary incontinence, and pain) from 181 to 365 days after allocation compared with before randomization. Secondary outcomes were use of medical services and adverse drug withdrawal effects. Results: Of a random sample of 2860 patients selected for potential enrollment, 2470 (86.4%) remained eligible after physician authorization, with 1237 randomized to the intervention and 1233 to usual care. A total of 1062 intervention patients (85.9%) were reached and agreed to enroll. Demographic variables were balanced. The median age of the 2470 patients was 80 (range, 76-104) years, and 1273 (51.5%) were women. In terms of race and ethnicity, 185 patients (7.5%) were African American, 234 (9.5%) were Asian or Pacific Islander, 220 (8.9%) were Hispanic, 1574 (63.7%) were White (63.7%), and 257 (10.4%) were of other (including American Indian or Alaska Native, Native Hawaiian, or >1 race or ethnicity) or unknown race or ethnicity. During follow-up, both the intervention and usual care groups had slight reductions in the number of medications dispensed (mean changes, -0.4 [95% CI, -0.6 to -0.2] and -0.4 [95% CI, -0.6 to -0.3], respectively), with no difference between the groups (P = .71). There were no significant changes in the prevalence of a geriatric condition in the usual care and intervention groups at the end of follow-up and no difference between the groups (baseline prevalence: 47.7% [95% CI, 44.9%-50.5%] vs 42.9% [95% CI, 40.1%-45.7%], respectively; difference-in-differences, 1.0 [95% CI, -3.5 to 5.6]; P = .65). No differences in use of medical services or adverse drug withdrawal effects were observed. Conclusions and Relevance: In this randomized clinical trial from an integrated care setting with various preexisting deprescribing workflows, a bundled hyperpolypharmacy deprescribing intervention was not associated with reduction in medication dispensing, prevalence of geriatric syndrome, utilization of medical services, or adverse drug withdrawal effects. Additional research is needed in less integrated settings and in more targeted populations. Trial Registration: ClinicalTrials.gov Identifier: NCT05616689.

Low-dose radiation augments vasculogenesis signaling through HIF-1-dependent and -independent SDF-1 induction.

The inflammatory response to ionizing radiation (IR) includes a proangiogenic effect that could be counterproductive in cancer but can be exploited for treating impaired wound healing. We demonstrate for the first time that IR stimulates hypoxia-inducible factor-1α (HIF-1α) up-regulation in endothelial cells (ECs), a HIF-1α-independent up-regulation of stromal cell-derived factor-1 (SDF-1), as well as endothelial migration, all of which are essential for angiogenesis. 5 Gray IR-induced EC HIF-1α and SDF-1 expression was greater when combined with hypoxia suggesting an additive effect. While small interfering RNA silencing of HIF-1α mRNA and abolition of HIF-1α protein induction down-regulated SDF-1 induction by hypoxia alone, it had little effect on SDF-1 induction by IR, demonstrating an independent pathway. SDF-1-mediated EC migration in hypoxic and/or radiation-treated media showed IR induced strong SDF-1-dependent migration of ECs, augmented by hypoxia. IR activates a novel pathway stimulating EC migration directly through the expression of SDF-1 independent of HIF-1α induction. These observations might be exploited for stimulation of wound healing or controlling tumor angiogenesis.

Novel splint allowing concurrent midface and occlusal control during orotracheal intubation.

Occlusal splints are used in craniomaxillofacial surgery to control the dental-bearing bony structures of the midface and mandible. They are created to guide the mobile bone segments into position based on the ideal or planned dental and facial relationships. For conventional orthognathic cases and maxillofacial trauma scenarios involving the dentition, a nasal endotracheal tube is required, allowing the teeth to be closed into intermaxillary fixation. However, in situations where access to the nasal cavity is required, such as concurrent rhinoplasty, or when higher osteotomies involving the midface are performed requiring advancement or manipulation of the nasal region, the nasal tube needs to be converted into an oral tube (J Clin Anesth 2011;23:342). This requires time and inconvenience and is a potentially dangerous maneuver in the setting of existing surgical edema, fluids, and manipulation. We report on a novel oral splint design allowing for both intermaxillary fixation to be established using an oral endotracheal tube while allowing for manipulation of the midface via the nasal cavity and not requiring a tube change intraoperatively.

Improved correction of supraorbital rim deformity in craniosynostosis by the "tilt" procedure.

Orbital rim deficits are a feature of metopic, unilateral coronal, and bilateral coronal craniosynostosis. Several procedures have been developed to address this issue, but relapse to the preoperative hypoplastic deformity and stunted growth of the fronto-orbital region are common. The authors describe a technique modification of the conventional lateral canthal advancement referred to as the orbital rim "tilt" procedure, which aims to preserve inferior bony support for the orbital rim and create projection with optimal proclination of the fronto-orbital complex.

Cutaneous low-dose radiation increases tissue vascularity through upregulation of angiogenic and vasculogenic pathways.

BACKGROUND/AIMS: Neovascularization involves angiogenesis and vasculogenesis mediated by cytokines and soluble chemokines. The predominant stimulus is ischemia, however, recent data suggest that ionizing radiation (IR) has angiogenic potential. In this study we evaluated whether IR increases vascularity and perfusion in vivo. METHODS: In wild-type mice, a full-thickness, pedicled skin flap was created and isolated for localized irradiation at a dose of 5 Gy. Serial Doppler analysis of the flap was performed. The skin flaps were then harvested at various time points for vascularity and histologic analysis. Blood was concurrently harvested for serum and hematopoietic progenitor cell population analysis. RESULTS: IR to an ischemic flap augmented the angiogenic cytokines SDF-1 and VEGF. Serum MMP-9 and s-kit levels, which are critical for progenitor cell mobilization, were also increased. When hematopoietic progenitor cells were evaluated by Sca1+/Flk1+ cells, a correlate 2-fold increase was seen compared to controls. When the flaps were examined, both vascularity and perfusion were increased. CONCLUSION: In this study we demonstrate that local, low-dose IR upregulates angiogenic chemokines and results in progenitor cell mobilization to the systemic circulation. There is a resultant increase in the vascularity of the irradiated flap, suggesting that the pro-angiogenic effects of IR can be harnessed locally.

A universal carrier test for the long tail of Mendelian disease.

Mendelian disorders are individually rare but collectively common, forming a 'long tail' of genetic disease. A single highly accurate assay for this long tail would allow the scaling up of the Jewish community's successful campaign of population screening for Tay-Sachs disease to the general population, thereby improving millions of lives, greatly benefiting minority health and saving billions of dollars. This need has been addressed by designing a universal carrier test: a non-invasive, saliva-based assay for more than 100 Mendelian diseases across all major population groups. The test has been exhaustively validated with a median of 147 positive and 525 negative samples per variant, demonstrating a multiplex assay whose performance compares favourably with the previous standard of care, namely blood-based single-gene carrier tests. Because the test represents a dramatic reduction in the cost and complexity of large-scale population screening, an end to many preventable genetic diseases is now in sight. Moreover, given that the assay is inexpensive and requires only a saliva sample, it is now increasingly feasible to make carrier testing a routine part of preconception care.

Improved diabetic wound healing through topical silencing of p53 is associated with augmented vasculogenic mediators.

Diabetes is characterized by several poorly understood phenomena including dysfunctional wound healing and impaired vasculogenesis. p53, a master cell cycle regulator, is upregulated in diabetic wounds and has recently been shown to play a regulatory roles in vasculogenic pathways. We have previously described a novel method to topically silence target genes in a wound bed with small interfering (si)RNA. We hypothesized that silencing p53 results in improved diabetic wound healing and augmentation of vasculogenic mediators. Paired 4-mm stented wounds were created on diabetic db/db mice. Topically applied p53 siRNA, evenly distributed in an agarose matrix, was applied to wounds at postwound day 1 and 7 (matrix alone and nonsense siRNA served as controls). Animals were sacrificed at postwound days 10 and 24. Wound time to closure was photometrically assessed, and wounds were harvested for histology, immunohistochemistry, and immunofluorescence. Vasculogenic cytokine expression was evaluated via Western blot, reverse transcription-polymerase chain reaction, and enzyme-linked immunosorbent assay. The ANOVA/t-test was used to determine significance (p≤ 0.05). Local p53 silencing resulted in faster wound healing with wound closure at 18±1.3 d in the treated group vs. 28±1.0 d in controls. The treated group demonstrated improved wound architecture at each time point while demonstrating near-complete local p53 knockdown. Moreover, treated wounds showed a 1.92-fold increase in CD31 endothelial cell staining over controls. Western blot analysis confirmed near-complete p53 knockdown in treated wounds. At day 10, VEGF secretion (enzyme-linked immunosorbent assay) was significantly increased in treated wounds (109.3±13.9 pg/mL) vs. controls (33.0±3.8 pg/mL) while reverse transcription-polymerase chain reaction demonstrated a 1.86-fold increase in SDF-1 expression in treated wounds vs. controls. This profile was reversed after the treated wounds healed and before closure of controls (day 24). Augmented vasculogenic cytokine profile and endothelial cell markers are associated with improved diabetic wound healing in topical gene therapy with p53 siRNA.

Data Management and Summary Statistics with PLINK.

PLINK is a versatile program which supports data management, quality control, and common statistical computations on matrices of genomic variant calls, in a computationally efficient manner. In population genomics, it is frequently used to take care of the "basics," so they do not need to be reimplemented when a new type of analysis needs to be performed on such a matrix. I describe several of these basic operations, and discuss uses and pitfalls.

Dose-dependent effect of radiation on angiogenic and angiostatic CXC chemokine expression in human endothelial cells.

Blood vessel growth is regulated by angiogenic and angiostatic CXC chemokines, and radiation is a vasculogenic stimulus. We investigated the effect of radiation on endothelial cell chemokine signaling, receptor expression, and migration and apoptosis. Human umbilical vein endothelial cells were exposed to a single fraction of 0, 5, or 20 Gy of ionizing radiation (IR). All vasculogenic chemokines (CXCL1-3/5-8) increased 3-13-fold after 5 or 20 Gy IR. 20 Gy induced a marked increase (1.6-4-fold) in angiostatic CXC chemokines. CXCR4 expression increased 3.5 and 7-fold at 48 h after 5 and 20 Gy, respectively. Bone marrow progenitor cell chemotaxis was augmented by conditioned media from cells treated with 5 Gy IR. Whereas 5 Gy markedly decreased intrinsic cell apoptosis (0 Gy=16%+/-3.6 vs. 5 Gy=4.5%+/-0.3), 20 Gy increased it (21.4%+/-1.2); a reflection of pro-survival angiogenic chemokine expression. Radiation induces a dose-dependent increase in pro-angiogenic CXC chemokines and CXCR4. In contrast, angiostatic chemokines and apoptosis were induced at higher (20 Gy) radiation doses. Cell migration improved significantly following 5 Gy, but not 20 Gy IR. Collectively, these data suggest that lower doses of IR induce an angiogenic cascade while higher doses produce an angiostatic profile.

Evaluation of a Pharmacist-Managed Antidiabetic Deprescribing Program in an Integrated Health Care System.

BACKGROUND: In the elderly, use of medications may increase the propensity for adverse drug events due to alterations in pharmacokinetic and pharmacodynamic profiles from normal aging processes. Deprescribing is the planned and supervised process of dose reduction or discontinuation of medications that may lead to harm or are no longer beneficial. While there are studies detailing strategies to deprescribe medications such as benzodiazepines and antipsychotics in nursing homes or for patients with dementia, there is a lack of guidance to safely deprescribe chronic medications, such as antidiabetics, for older patients in the community setting. OBJECTIVE: To evaluate the risk of hypoglycemia and other outcomes of pharmacist-managed deprescribing on selected antidiabetic medications under the guidance of a standardized program compared with usual care within an integrated health care system. METHODS: This was a retrospective propensity score-matched cohort study. The pharmacist-managed deprescribing group included patients who were enrolled in the deprescribing program between July 1, 2016, and June 30, 2017. The usual care group included eligible patients who did not receive the deprescribing intervention and were matched to the deprescribing group using propensity score matching (PSM). Baseline demographics and clinical variables were used for matching. Patients were followed for 6 months or the end of membership or death, whichever occurred first. Primary outcome was the risk of hypoglycemia. Secondary outcomes included risk of hyperglycemia, proportion of patients at goal (A1c), change in A1c, change in monthly antidiabetic drug cost, and all-cause mortality. Outcomes were analyzed using descriptive statistics and multivariant regression or Cox proportional hazard models when appropriate. RESULTS: After PSM, 685 patients in the deprescribing group and 2,055 patients in the usual care group were similar in age, gender, weight, and comorbidity burden (mean [SD] age 82.4 [5.4] years, 48% female, mean [SD] weight 81.7 [19.2] kg, mean [SD] Charlson Comorbidity Index score 3.2 [1.6]). Compared with the usual care group, the deprescribing group had a lower risk of hypoglycemia (1.5% vs. 3.1%, P < 0.02; adjusted odds ratio 0.42, P < 0.01). As for the secondary outcomes, the deprescribing group had a greater change (SD) in A1c (0.3 [0.6] vs. 0.2 [0.7] P < 0.01) and lower all-cause mortality (2.3% vs 5.6%, P < 0.01; adjusted hazard ratio 0.35, P < 0.01). There were no differences observed in the risk of hyperglycemia, proportion of patients at goal A1c < 7%, and change in monthly antidiabetic drug costs between the 2 groups. CONCLUSIONS: There are currently no studies to our knowledge that evaluate the outcomes of a pharmacist-managed deprescribing program targeting antidiabetic medications. The results of our study showed that deprescribing of selected antidiabetics reduced the risk of hypoglycemia and may have mortality benefit in elderly patients with well-controlled type 2 diabetes, who are taking medications that can cause hypoglycemia. Further and longer studies are needed to validate these benefits. DISCLOSURES: No outside funding was provided to support this research study. The authors of this study have no actual or potential conflicts of interest to report. Parts of this study were presented in a nonreviewed resident poster at the Academy of Managed Care Pharmacy Managed Care and Specialty Pharmacy Annual Meeting; April 23-26, 2018; Boston, MA.

Design and implementation of population-based specialty care programs.

PURPOSE: The development, implementation, and scaling of 3 population-based specialty care programs in a large integrated healthcare system are reviewed, and the role of clinical pharmacy services in ensuring safe, effective, and affordable care is highlighted. SUMMARY: The Kaiser Permanente (KP) integrated healthcare delivery model allows for rapid development and expansion of innovative population management programs involving pharmacy services. Clinical pharmacists have assumed integral roles in improving the safety and effectiveness of high-complexity, high-cost care for specialty populations. These roles require an appropriate practice scope and are supported by an advanced electronic health record with disease registries and electronic surveillance tools for care-gap identification. The 3 specialty population programs described were implemented to address variation or unrecognized gaps in care for at-risk specialty populations. The Home Phototherapy Program has leveraged internal partnerships with clinical pharmacists to improve access to cost-effective nonpharmacologic interventions for psoriasis and other skin disorders. The Multiple Sclerosis Care Program has incorporated clinical pharmacists into neurology care in order to apply clinical guidelines in a systematic manner. The KP SureNet program has used clinical pharmacists and data analytics to identify opportunities to prevent drug-related adverse outcomes and ensure timely follow-up. CONCLUSION: Specialty care programs improve quality, cost outcomes, and the patient experience by appropriating resources to provide systematic and targeted care to high-risk patients. KP leverages an integration of people, processes, and technology to develop and scale population-based specialty care.

Gastrostomy Placement Rates in Infants with Pierre Robin Sequence: A Comparison of Tongue-Lip Adhesion and Mandibular Distraction Osteogenesis.

BACKGROUND: This study was conducted to compare the gastrostomy rates in infants with Pierre Robin sequence treated with tongue-lip adhesion or mandibular distraction osteogenesis. METHODS: This was a retrospective study of symptomatic plastic and reconstructive surgery patients treated over an 8-year period. The primary predictor variable was surgical intervention (tongue-lip adhesion or distraction osteogenesis). Secondary predictor variables were categorized as demographic and clinical factors. The primary outcome was the need for gastrostomy tube placement. Secondary outcomes were complication rates, costs, and length of stay. RESULTS: Thirty-one tongue-lip adhesion and 30 distraction osteogenesis patients were included in the study. The groups were statistically comparable with regard to demographic and clinical factors (p > 0.18). Gastrostomy rates were higher in patients who underwent tongue-lip adhesion (48 percent) versus those who underwent distraction osteogenesis (16.7 percent; p = 0.008). In an adjusted model, subjects undergoing tongue-lip adhesion were more likely to require gastrostomy tube for nutritional support (OR, 6.5; 95 percent CI, 1.7 to 25.2; p = 0.007). There were two major complications in the tongue-lip adhesion group and none in the distraction osteogenesis group. There were three minor complications in the tongue-lip adhesion group and five in the distraction osteogenesis group. Total operating room costs were higher for distraction osteogenesis (p = 0.05), and total hospital costs and length of stay were higher for tongue-lip adhesion (p < 0.05). CONCLUSIONS: Among infants with symptomatic Pierre Robin sequence, treatment by distraction osteogenesis is associated with a lower risk for gastrostomy placement for nutritional support. Hospital costs are higher for tongue-lip adhesion. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Pedicle versus free flap reconstruction in patients receiving intraoperative brachytherapy.

Introduction This study compared complication rates between pedicle flaps and free flaps used for resurfacing of intraoperative brachytherapy (IOBT) implants placed following head and neck tumour extirpation to help clarify the ideal reconstructive procedure for this scenario. Patients and methods A retrospective review of reconstructions with IOBT at our institution was conducted. Patient and treatment details were recorded, as were the number and type of flap complications, including re-operations. Logistic regressions compared complications between flap groups. Results Fifty free flaps and 55 pedicle flaps were included. On multivariate analysis, free flap reconstruction with IOBT was significantly associated with both an increased risk of having any flap complication (OR = 2.9, p = 0.037) and with need for operative revision (OR = 3.5, p = 0.048) compared to pedicle flap reconstruction. Conclusions In the setting of IOBT, free flaps are associated with an increased risk of having complications and requiring operative revisions.

Extensive sequencing of seven human genomes to characterize benchmark reference materials.

The Genome in a Bottle Consortium, hosted by the National Institute of Standards and Technology (NIST) is creating reference materials and data for human genome sequencing, as well as methods for genome comparison and benchmarking. Here, we describe a large, diverse set of sequencing data for seven human genomes; five are current or candidate NIST Reference Materials. The pilot genome, NA12878, has been released as NIST RM 8398. We also describe data from two Personal Genome Project trios, one of Ashkenazim Jewish ancestry and one of Chinese ancestry. The data come from 12 technologies: BioNano Genomics, Complete Genomics paired-end and LFR, Ion Proton exome, Oxford Nanopore, Pacific Biosciences, SOLiD, 10X Genomics GemCode WGS, and Illumina exome and WGS paired-end, mate-pair, and synthetic long reads. Cell lines, DNA, and data from these individuals are publicly available. Therefore, we expect these data to be useful for revealing novel information about the human genome and improving sequencing technologies, SNP, indel, and structural variant calling, and de novo assembly.