Biomechanical Performance of Biodegradable Screw Fixation in Mandibular Distraction Osteogenesis.

Internal distraction devices are commonly used in congenital micrognathia. The eventual need for device and screw removal can be challenging, requiring extensive dissection and disturbance of bone regenerate. Bioabsorbable poly-L-lactide (PLLA) screws, compared to traditional titanium screws, simplify device removal. Previous in vivo studies have found that the maximal compressive force generated by mandibular distraction is 69.4N. We hypothesized that PLLA screws could support these compressive/distraction forces. Ten mandibles were obtained from 5 canine cadavers. Paired mandibles from the same cadaver were each fixated to a mandibular distractor with eight screws (either titanium or PLLA). Devices were each set to 15 and 30 mm of distraction distance. Compression force of 80 N was then generated parallel to the axis of the distraction device. Distractor displacement was measured to detect any mechanical failure during this pre-set load. Finally, if no failure was observed at 80 N, a load-to-failure compression test was done in the PLLA group to determine the mechanical failure point. All distractors in both the titanium and PLLA screw groups withstood 80 N of compression without failure. When the load-to-failure test was performed in the PLLA group, the average device failure point was 172.8 N (range 148-196 N). Review of high-frame-rate video demonstrated that all failures occurred due to the PLLA screws breaking or falling out. Bioabsorbable PLLA screws can withstand compressive forces more than double that of the maximal in vivo forces needed during mandibular distraction. These screws may be an acceptable alternative for the fixation of internal mandibular distractors.

Colonic stenting for malignant obstructions-A review of current indications and outcomes.

BACKGROUND: Colonic stenting has emerged as preferred palliative treatment for left sided malignant obstructions. It shortens hospital stays, decreases healthcare cost, reduces permanent stoma rates, and expedites the start of chemotherapy. The role of stenting as a bridge-to-surgery remains unsettled. DATA SOURCE: For this paper the recommendations of the American and European society of gastroenterology and colorectal surgery were reviewed. We will discuss the benefits and risks of stenting in palliative setting and as bridge-to-surgery. Quality of life, hospital stay, and health care cost will also be considered. CONCLUSION: Non-traversable colon masses during endoscopy are considered a risk factor of development of intestinal obstruction but preventive stent placement in patients without obstructive symptoms is not recommended. The risk of technical or clinical failure is significant at 25%. If stent placement allows neoadjuvant chemotherapy, it may increase the rate of R0 resections. Perforations may raise local recurrence and mortality rates.

Randomized controlled trial of fractionated laser resurfacing on aged skin as prophylaxis against actinic neoplasia.

BACKGROUNDThe loss of insulin-like growth factor 1 (IGF-1) expression in senescent dermal fibroblasts during aging is associated with an increased risk of nonmelanoma skin cancer (NMSC). We tested how IGF-1 signaling can influence photocarcinogenesis during chronic UVB exposure to determine if fractionated laser resurfacing (FLR) of aged skin, which upregulates dermal IGF-1 levels, can prevent the occurrence of actinic keratosis (AK) and NMSC.METHODSA human skin/immunodeficient mouse xenografting model was used to test the effects of a small molecule inhibitor of the IGF-1 receptor on chronic UVB radiation. Subsequently, the durability of FLR treatment was tested on a cohort of human participants aged 65 years and older. Finally, 48 individuals aged 60 years and older with considerable actinic damage were enrolled in a prospective randomized clinical trial in which they underwent a single unilateral FLR treatment of one lower arm. Numbers of AKs/NMSCs were recorded on both extremities for up to 36 months in blinded fashion.RESULTSXenografting studies revealed that chronic UVB treatment with a topical IGF-1R inhibitor resulted in a procarcinogenic response. A single FLR treatment was durable in restoring appropriate UVB response in geriatric skin for at least 2 years. FLR resulted in sustained reduction in numbers of AKs and decreased numbers of NMSCs in the treated arm (2 NMSCs) versus the untreated arm (24 NMSCs).CONCLUSIONThe elimination of senescent fibroblasts via FLR reduced the procarcinogenic UVB response of aged skin. Thus, wounding therapies are a potentially effective prophylaxis for managing high-risk populations.TRIAL REGISTRATIONClinicalTrials.gov (NCT03906253).FUNDINGNational Institutes of Health, Veterans Administration.

Do contradictions in TQIP measures affect perceptions of quality. An analysis of TQIP definitions on quality outcomes for placement of ICP monitoring at a single level one trauma center.

BACKGROUND: TQIP quality measures as currently defined on occasion provide discordant conclusions. A recent TQIP report of an urban level one-trauma center suggested a low employment of ICP monitoring while also demonstrating aggressive implementation of ICP monitoring (ave. within 90 min of arrival). This apparent contradiction leads to the question; Does TQIP define correctly the patient cohort who would most benefit from ICP monitoring? METHODS: A retrospective IRB approved review of all patients reported to TQIP with severe TBI was performed at an ACS verified level one trauma center. All patients admitted to the TS during the TQIP study period were reviewed. Demographic data as well as AIS, ISS, GCS, injury type and outcomes were reviewed. Data were reported as aggregate. RESULTS: Trauma registry review determined 108 patients met the TQIP definition for severe TBI. Analysis of these patients revealed only 58%(63) met clinical criteria for severe TBI. In this group 45.4%(49) suffered non-survivable TBI. ICP monitoring was not initiated in this subgroup of patients. 42%(45) of the patients were determined to have mild to moderate TBI. In this cohort the initial GCS reported in the trauma registry overestimated the severity of the TBI in 19.4%(21) of the patients. ICP monitoring was initiated 29%(30) patients. The analysis would indicate 13%(14) would have benefited from ICP monitoring indicating an 15%(16) over utilization. The majority of these patients sustained meaningful neurologic recovery indicating a better-defined criterion may be necessary to determine when ICP monitoring is a quality indicator. CONCLUSION: This study indicates the current TQIP definition used to justify ICP monitoring appears to overestimate the number of patients who would benefit from ICP monitoring. The corrected quality analysis indicates an overutilization rather than an underutilization of ICP monitoring. Further study of the effect of definitions on quality measures should be considered.

Enhanced Platelet-Activating Factor Synthesis Facilitates Acute and Delayed Effects of Ethanol-Intoxicated Thermal Burn Injury.

Thermal burn injuries in patients who are alcohol-intoxicated result in greater morbidity and mortality. Murine models combining ethanol and localized thermal burn injury reproduce the systemic toxicity seen in human subjects, which consists of both acute systemic cytokine production with multiple organ dysfunction, as well as a delayed systemic immunosuppression. However, the exact mechanisms for these acute and delayed effects are unclear. These studies sought to define the role of the lipid mediator platelet-activating factor in the acute and delayed effects of intoxicated burn injury. Combining ethanol and thermal burn injury resulted in increased enzymatic platelet-activating factor generation in a keratinocyte cell line in vitro, human skin explants ex vivo, as well as in murine skin in vivo. Further, the acute increase in inflammatory cytokines, such as IL-6, and the systemic immunosuppressive effects of intoxicated thermal burn injury were suppressed in mice lacking platelet-activating factor receptors. Together, these studies provide a potential mechanism and treatment strategies for the augmented toxicity and immunosuppressive effects of thermal burn injury in the setting of acute ethanol exposure, which involves the pleotropic lipid mediator platelet-activating factor.

Radiation therapy generates platelet-activating factor agonists.

Pro-oxidative stressors can suppress host immunity due to their ability to generate oxidized lipid agonists of the platelet-activating factor-receptor (PAF-R). As radiation therapy also induces reactive oxygen species, the present studies were designed to define whether ionizing radiation could generate PAF-R agonists and if these lipids could subvert host immunity. We demonstrate that radiation exposure of multiple tumor cell lines in-vitro, tumors in-vivo, and human subjects undergoing radiation therapy for skin tumors all generate PAF-R agonists. Structural characterization of radiation-induced PAF-R agonistic activity revealed PAF and multiple oxidized glycerophosphocholines that are produced non-enzymatically. In a murine melanoma tumor model, irradiation of one tumor augmented the growth of the other (non-treated) tumor in a PAF-R-dependent process blocked by a cyclooxygenase-2 inhibitor. These results indicate a novel pathway by which PAF-R agonists produced as a byproduct of radiation therapy could result in tumor treatment failure, and offer important insights into potential therapeutic strategies that could improve the overall antitumor effectiveness of radiation therapy regimens.