Surgically Treated Femoral Neck Stress Fractures Are Likely to Result in Military Separation During Basic Combat Training.

BACKGROUND: Femoral neck stress fractures are a common condition affecting military service members, most noticeably during basic combat training. Previous studies have investigated the risk factors for femoral neck stress fracture development in basic trainees and outcomes associated with treatment; however, few studies have focused on operatively treated femoral neck stress fracture in the military trainee. Doing so would be important not only for the military, but also providers caring for athletes, such as distance runners, who have a heightened risk for femoral neck stress fracture development. QUESTIONS/PURPOSES: (1) What proportion of US Army trainees completing basic combat training at Fort Jackson, SC, USA, who undergo surgery for femoral neck stress fracture during basic training subsequently leave military service because of the injury? (2) What factors are related to the patient or the fracture are associated with a higher likelihood of military separation? (3) What factors on the initial MRI are associated with progression of the stress fracture extent? METHODS: A retrospective study of a longitudinally maintained database of stress injuries involving basic combat trainees from a single military post was reviewed over a 3-year period. Inclusion criteria included basic trainees undergoing surgery for a femoral neck stress fracture between January 2018 and June 2020 with a minimum of 1-year follow-up. Surgery was indicated for service members with complete and tension-sided femoral neck stress fractures and those with high risk compression-sided stress fractures, generally representing fractures involving more than 50% of the femoral neck width. Over the study period, 57 service members (51% [29 of 57] women with a mean age of 24 years) underwent surgery for a femoral neck stress fracture, and all 57 had a minimum of 1-year follow-up. Identified service members underwent independent data collection including injury and radiographic parameters based on chart and imaging review. Documented fracture line progression on repeat imaging was present in 39% of service members, with a mean fracture line progression of 55% of the femoral neck width. Service members were subdivided based upon the ability to return to military service at 1 year. Univariate analysis was performed using patient and injury variables to identify factors associated with the ability to return to military service. RESULTS: Overall, 58% (33 of 57) of service members who had a femoral neck stress fracture treated surgically underwent military separation. A higher proportion of service members who demonstrated fracture line progression leading to surgical treatment remained in the military (58% [14 of 24] versus 30% [10 of 33]; odds ratio 0.3 [95% confidence interval (CI) 0.1 to 0.9]; p = 0.03). With the numbers available, we found no other patient- or fracture-related variables associated with military separation, although we suspect we may have been underpowered on some of these comparisons, in particular gender (61% [20 of 33] of individuals separated after surgery for this injury were women compared with 38% [9 of 24] who were retained; OR 2.6 [95% CI 0.9 to 7.56]; p = 0.09). The extent of osseous edema on T1-weighted imaging in association with a hip effusion demonstrated a significant positive correlation with final fracture percentage (r = 0.62; p = 0.003). CONCLUSION: Military service members with a femoral neck stress fracture initially managed nonoperatively but with progression of the fracture line requiring surgical intervention were more likely to return to military duties and complete basic combat training, suggesting that early diagnosis of femoral neck stress fractures may be associated with better functional recovery after surgical treatment. Additionally, the extent of the osseous edema on initial MRI T1-weighted imaging sequences may help predict the final extent of femoral neck stress fractures on repeat imaging. Further investigations should incorporate patient-reported outcomes and further explore factors associated with fracture progression and the inability to return to active duty or sport. LEVEL OF EVIDENCE: Level III, therapeutic study.

Vitamin C to Pregnant Smokers Persistently Improves Infant Airway Function to 12†Months of Age: A Randomised Trial.

BACKGROUND: Vitamin C (500 mg·day-1) supplementation for pregnant smokers has been reported to increase newborn pulmonary function and infant forced expiratory flows (FEFs) at 3 months of age. Its effect on airway function through 12 months of age has not been reported. OBJECTIVE: To assess whether vitamin C supplementation to pregnant smokers is associated with a sustained increased airway function in their infants through 12 months of age. METHODS: This is a prespecified secondary outcome of a randomised, double-blind, placebo-controlled trial that randomised 251 pregnant smokers between 13 and 23 weeks of gestation: 125 to 500 mg·day-1 vitamin C and 126 to placebo. Smoking cessation counselling was provided. FEFs performed at 3 and 12 months of age were analysed by repeated measures analysis of covariance. RESULTS: FEFs were performed in 222 infants at 3 months and 202 infants at 12 months of age. The infants allocated to vitamin C had significantly increased FEFs over the first year of life compared to those allocated to placebo. The overall increased flows were: 40.2 mL·sec-1 for FEF75 (adjusted 95% CI for difference 6.6 to 73.8; p=0.025); 58.3 mL·sec-1 for FEF50 (95% CI 10.9 to 105.8; p=0.0081); and 55.1 mL·sec-1 for FEF25-75 (95% CI, 9.7 to 100.5; p=0.013). CONCLUSIONS: In offspring of pregnant smokers randomised to vitamin C versus placebo, vitamin C during pregnancy was associated with a small but significantly increased airway function at 3 and 12 months of age, suggesting a potential shift to a higher airway function trajectory curve. Continued follow-up is underway.

Oral Vitamin C (500 mg/d) to Pregnant Smokers Improves Infant Airway Function at 3 Months (VCSIP). A Randomized Trial.

Rationale: We reported a randomized trial demonstrating daily supplemental vitamin C to pregnant smokers significantly improved newborn pulmonary function tests. The current study tests these results in a new cohort using infant pulmonary function tests. Objectives: To determine if infants of pregnant smokers randomized to daily supplemental vitamin C would have improved forced expiratory flows (FEFs) at 3 months of age compared with those randomized to placebo, and to investigate the association of the α5 nicotinic acetylcholine receptor. Methods: A randomized, double-blind, placebo-controlled trial was conducted at three centers. Two hundred fifty-one pregnant smokers were randomized at 13-23 weeks of gestation: 125 randomized to vitamin C (500 mg/d) and 126 to placebo. Measurements and Main Results: The primary outcome was FEF75 at 3 months of age performed with the raised volume rapid thoracic compression technique (Jaeger/Viasys). FEF50 and FEF25-75 obtained from the same expiratory curves were prespecified secondary outcomes. The infants of pregnant smokers randomized to vitamin C (n = 113) had the following FEFs at 3 months of age compared with those randomized to placebo (n = 109) as measured by FEF75 (200.7 vs. 188.7 ml/s; adjusted 95% confidence interval [CI] for difference, -3.33 to 35.64; P = 0.10), FEF50 (436.7 vs. 408.5 ml/s; adjusted 95% CI for difference, 6.10-61.30; P = 0.02), and FEF25-75 (387.4 vs. 365.8 ml/s; adjusted 95% CI for difference, 0.92-55.34; P = 0.04). Infant FEFs seemed to be negatively associated with the maternal risk alleles for the α5 nicotinic acetylcholine receptor (rs16969968). Conclusions: Although the primary outcome of FEF75 was not improved after vitamin C supplementation to pregnant smokers, the predetermined secondary outcomes FEF50 and FEF25-75 were significantly improved. These results extend our previous findings and demonstrate improved airway function (FEF50 and FEF25-75) at 3 months of age in infants after vitamin C supplementation to pregnant smokers. Clinical trial registered with www.clinicaltrials.gov (NCT01723696).

High-Throughput Phenotyping Approach for Screening Major Carotenoids of Tomato by Handheld Raman Spectroscopy Using Chemometric Methods.

Our objective was to develop a rapid technique for the non-invasive profiling and quantification of major tomato carotenoids using handheld Raman spectroscopy combined with pattern recognition techniques. A total of 106 samples with varying carotenoid profiles were provided by the Ohio State University Tomato Breeding and Genetics program and Lipman Family Farms (Naples, FL, USA). Non-destructive measurement from the surface of tomatoes was performed by a handheld Raman spectrometer equipped with a 1064 nm excitation laser, and data analysis was performed using soft independent modelling of class analogy (SIMCA)), artificial neural network (ANN), and partial least squares regression (PLSR) for classification and quantification purposes. High-performance liquid chromatography (HPLC) and UV/visible spectrophotometry were used for profiling and quantification of major carotenoids. Seven groups were identified based on their carotenoid profile, and supervised classification by SIMCA and ANN clustered samples with 93% and 100% accuracy based on a validation test data, respectively. All-trans-lycopene and ß-carotene levels were measured with a UV-visible spectrophotometer, and prediction models were developed using PLSR and ANN. Regression models developed with Raman spectra provided excellent prediction performance by ANN (rpre = 0.9, SEP = 1.1 mg/100 g) and PLSR (rpre = 0.87, SEP = 2.4 mg/100 g) for non-invasive determination of all-trans-lycopene in fruits. Although the number of samples were limited for ß-carotene quantification, PLSR modeling showed promising results (rcv = 0.99, SECV = 0.28 mg/100 g). Non-destructive evaluation of tomato carotenoids can be useful for tomato breeders as a simple and rapid tool for developing new varieties with novel profiles and for separating orange varieties with distinct carotenoids (high in ß-carotene and high in cis-lycopene).

Hyperglycaemia induced by chronic i.p. and oral glucose loading leads to hypertension through increased Na+ retention in proximal tubule.

NEW FINDINGS: What is the central question of the study? Chronic glucose feeding accompanied by glucose injection (i.p.) causes sustained hyperglycaemia and hypertension in rats. The exact reason for the hypertension is not known. We explore some molecular pathways of the renal proximal tubule that might promote Na+ retention. What is the main finding and its importance? Development of hypertension was mediated by upregulation of the renal renin-angiotensin system and oxidative stress, acting via the Na+ -K+ -ATPase α1 -subunit in the proximal tubule, which appears to pump intracellular Na+ into the extracellular space, increasing Na+ reabsorption and blood pressure. Targeting the Na+ -K+ -ATPase α1 -subunit might provide a therapeutic strategy for treatment of hypertension. Feeding animals glucose-, fructose-, sucrose- and fat-enriched diets can lead to diet-induced hyperglycaemia, the severity of which largely depends on the types and concentrations of the nutrients used and duration of the dietary intervention. As a dietary intervention strategy, we adopted glucose-enriched diet and drinking water, with i.p. glucose injection at a dose previously determined to be effective to establish a sustained hyperglycaemia over a period of 2 weeks. We used four groups of Sprague-Dawley rats: control; glucose treated; glucose plus tempol treated; and glucose plus captopril treated. Blood glucose concentrations started to increase gradually from day 3, peaked (321 mg dl-1 ) at day 12 and remained at similar levels until the end of the study on day 14 in the glucose treated-group compared with the control group. In contrast, the tempol- and captopril-treated groups showed significantly high glucose concentrations only in the second week. The plasma insulin concentration was significantly increased in glucose-treated animals but not in tempol- and captopril-treated groups when compared with the control rats. We also observed elevated blood pressure in the glucose-treated group compared with the control group, which can be attributed to the increase in angiotensin II concentrations from 46.67 to 99 pg ml-1 (control versus glucose), increased oxidative stress in the cortical proximal tubule (PT), decreased urine flow, and increased expression and activity of the PT-specific α1 -subunit of Na+ -K+ -ATPase in the renal cortex, which is responsible for increased sodium reabsorption from epithelial cells of PT into the peritubular capillaries, leading to increased blood volume and eventual blood pressure. All these events were reversed in captopril- and tempol-treated animals.

Outcomes of biceps tenodesis in an active duty population.

Pathology affecting the long head of the biceps tendon and its insertion is a frequent cause of shoulder pain in the active duty military population. The purpose of this investigation was to evaluate functional outcomes of subpectoral biceps tenodesis in an active duty population. A retrospective case series of 22 service members who underwent biceps tenodesis was performed and Shoulder Pain and Disability Indexes (SPADI) and Disabilities of the Arm, Shoulder and Hand (DASH) scores were obtained preoperatively and at 6 months. Additionally, a review of each subject's physical profile was performed 6 months after surgery to determine continued physical limitations and one's ability to deploy. There was a statistically significant improvement in SPADI and DASH scores comparing preoperative versus postoperative outcomes. Although five subjects (22%) continued to have a restriction to performing push-ups on the Army Physical Fitness Test, all were deemed deployable from a physical standpoint. The results of this review suggest that active duty personnel undergoing biceps tenodesis have significant functional improvement at 6 months. Additionally, very few have long-term physical limitations or deployment restrictions.

Haemodynamic consequences of recurrent insulin-induced hypoglycaemia.

1. Recurring insulin-induced hypoglycaemia (RIIH) often occurs during the therapeutic management of insulin-dependent diabetes mellitus. Controversy currently exists in the literature as to the ability of insulin and/or hypoglycaemia to promote hypertension. Could insulin and/or hypoglycaemia promote adverse pressor effects? If so, under what conditions and through what mechanism? Thus, the present study was performed to evaluate the hypothesis that RIIH produces hypertension via induction of heme oxygenase (HO)-1, promoting a significant increase in endogenous carbon monoxide (CO). 2. Male Sprague-Dawley rats were treated for 2 weeks with varying doses of insulin (1, 3, 5, 7 and 9 U/kg, s.c.) or vehicle and fed normal rat chow or a zinc diet (1 mmol/L) for 2 weeks. Tail-cuff blood pressure, food intake and blood glucose states were monitored daily. 3. A dose-dependent decrease in blood glucose was observed in insulin-treated rats. Blood pressure was significantly elevated in rats treated with 9 and 7 U/kg insulin compared with those treated with other doses of insulin. However, there was no change in urine output among the groups. Feeding of a high-zinc diet to rats treated with 7 U/kg insulin and treatment with the HO-1 inhibitor zinc deuteroporphyrin 2,4-bis glycol (ZnDPBG; 20 mg/kg) after insulin injection resulted in a significant reduction in blood pressure compared with 7 U/kg insulin injection alone. In addition, HO-1 protein levels in the heart and kidney and endogenous CO levels were reduced in 7 U/kg insulin-treated rats fed the high-zinc diet compared with those treated with the same dose of insulin alone. 4. The results of the present study demonstrate that RIIH promotes hypertension and that restoration of normal CO levels with a high-zinc diet and ZnDPBG reduces blood pressure.

Evaluation of immediate postoperative complications and outcomes among military personnel treated for spinal trauma in Afghanistan: a cohort-control study of 50 cases.

STUDY DESIGN: Retrospective case-control study. OBJECTIVE: The objective of the study was to compare neurological outcomes and complication rates between a series of combat-injured patients treated in Afghanistan (AFG) and those treated at Landstuhl Regional Medical Center (LRMC). SUMMARY OF BACKGROUND DATA: At present, no studies have addressed the ideal timing and setting for surgical stabilization in combat-injured soldiers who sustain spinal trauma. METHODS: Soldiers who sustained spine injuries while deployed to Afghanistan and who underwent surgery in theater or at LRMC between 2010 and 2011 were identified. Demographic information, injury-specific data, neurological status, type of surgical intervention, postoperative complications, and need for additional surgery were abstracted for all patients. Neurological improvement was the primary dependent variable. Secondary variables included the risk of developing complications and the need for additional surgery. Statistical analysis was performed using t tests, and the Fisher exact test was used for categorical variables. RESULTS: Between 2010 and 2011, 30 individuals were treated in AFG, and 20 received surgery at LRMC. Neurological improvement occurred in 10% of AFG patients and 5% of those treated at LRMC. Complications occurred in 40% of AFG patients and in 20% of the LRMC group. Twenty-three percent of AFG patients required additional spine surgery after leaving Afghanistan. There was no statistical difference in neurological improvement between the AFG and LRMC groups (P=0.64). Soldiers who received surgery in AFG were at significantly increased risk of requiring additional procedures (P=0.03). CONCLUSIONS: Soldiers treated in theater did not have statistically higher rates of neurological improvement as compared with those treated at LRMC. Patients treated in-theater were at elevated risk for the need for additional surgery. This study is among the first to evaluate clinical outcomes after surgical intervention for war-related spinal trauma. LEVEL OF EVIDENCE: Level III (case-control).

Vitamin C supplementation for pregnant smoking women and pulmonary function in their newborn infants: a randomized clinical trial.

IMPORTANCE: Maternal smoking during pregnancy adversely affects offspring lung development, with lifelong decreases in pulmonary function and increased asthma risk. In a primate model, vitamin C blocked some of the in-utero effects of nicotine on lung development and offspring pulmonary function. OBJECTIVE: To determine if newborns of pregnant smokers randomized to receive daily vitamin C would have improved results of pulmonary function tests (PFTs) and decreased wheezing compared with those randomized to placebo. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind trial conducted in 3 sites in the Pacific Northwest between March 2007 and January 2011. One hundred fifty-nine newborns of randomized pregnant smokers (76 vitamin C treated and 83 placebo treated) and 76 newborns of pregnant nonsmokers were studied with newborn PFTs. Follow-up assessment including wheezing was assessed through age 1 year, and PFTs were performed at age 1 year. INTERVENTIONS: Pregnant women were randomized to receive vitamin C (500 mg/d) (n = 89) or placebo (n = 90). MAIN OUTCOMES AND MEASURES: The primary outcome was measurement of newborn pulmonary function (ratio of the time to peak tidal expiratory flow to expiratory time [TPTEF:TE] and passive respiratory compliance per kilogram [Crs/kg]) within 72 hours of age. Secondary outcomes included incidence of wheezing through age 1 year and PFT results at age 1 year. A subgroup of pregnant smokers and nonsmokers had genotyping performed. RESULTS: Newborns of women randomized to vitamin C (n = 76), compared with those randomized to placebo (n = 83), had improved pulmonary function as measured by TPTEF:TE (0.383 vs 0.345 [adjusted 95% CI for difference, 0.011-0.062]; P = .006) and Crs/kg (1.32 vs 1.20 mL/cm H2O/kg [95% CI, 0.02-0.20]; P = .01). Offspring of women randomized to vitamin C had significantly decreased wheezing through age 1 year (15/70 [21%] vs 31/77 [40%]; relative risk, 0.56 [95% CI, 0.33-0.95]; P = .03). There were no significant differences in the 1-year PFT results between the vitamin C and placebo groups. The effect of maternal smoking on newborn lung function was associated with maternal genotype for the α5 nicotinic receptor (rs16969968) (P < .001 for interaction). CONCLUSIONS AND RELEVANCE: Supplemental vitamin C taken by pregnant smokers improved newborn PFT results and decreased wheezing through 1 year in the offspring. Vitamin C in pregnant smokers may be an inexpensive and simple approach to decrease the effects of smoking in pregnancy on newborn pulmonary function and respiratory morbidities. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00632476.

The combat burst fracture study--results of a cohort analysis of the most prevalent combat specific mechanism of major thoracolumbar spinal injury.

INTRODUCTION: In 2009-2010, military physicians hypothesized that a new pattern of spinal injury had emerged, resulting from improvised explosive device assault on up-armored vehicles, associated with a high rate of point of first contact fracture and neurological injury-the combat burst fracture. We sought to determine the incidence of all thoracolumbar (TL) burst fractures and combat burst fractures in 2009-2010 as compared to two antecedent years. METHODS: A screening process identified all individuals who sustained TL burst fractures in the time-period studied. Demographics, injury-specific characteristics, mechanism of injury, surgical interventions and early complications were recorded. Incidence rates were calculated for the three time periods using total deployed troop-strength and number of LRMC combat admissions as denominators. The incidences of TL burst fractures within each year group and by mechanism were compared, and clinical characteristics and process of care were described. RESULTS: Between 2007-2010, 65 individuals sustained a TL burst fracture. The incidence of these injuries in 2009-2010 was 2.1 per 10,000 soldier-years and accounted for 3.0 % of LRMC combat-casualty admissions, a significant increase from 0.6 % and 1.1 % in 2007-2008 and 2008-2009, respectively (p ≤ 0.001). In 2009-2010, US soldiers were 3.4-4.6 times more likely to sustain a TL burst fracture compared to 2008-2009 and 2007-2008 (p < 0.001), and the most common mechanism of injury was IED vs. vehicle (65 %)-the combat burst fracture mechanism. Neurological deficits were present in 43 % of TL burst fractures and 1/3 were complete injuries. Spinal fixation was performed in 68 % overall and 74 % of combat burst fractures. CONCLUSIONS: There was a 3.4- to 4.6-fold increase in TL burst fractures in 2009-2010 compared to antecedent years. The primary driver of this phenomenon was the marked increased in combat burst fractures. Mitigating/preventing the mechanism behind this major spinal injury is a key research initiative for the US military. Level of Evidence III (Case-control).

Consensus and Equipose in the Management of Military Trainee Femoral Neck Stress Fractures: A Survey of Military Surgeons.

BACKGROUND: Femoral neck stress fractures (FNSFs) are a unique injury pattern not commonly treated in the civilian trauma population; however, it is particularly high with military trainees engaged in basic combat training. To date, no study has surveyed a population of military orthopedic surgeons on treatment preferences for military service members (SMs) with FNSF. QUESTIONS: We aim to evaluate the extent of clinical equipoise that exists in the management of these injuries, hypothesizing that there would be consensus in the factors dictating surgical and non-surgical intervention for FNSF. PATIENTS AND METHODS: A 27-question survey was created and sent to U.S. military orthopedic surgeon members of the Society of Military Orthopaedic Surgeons. The survey was designed in order to gather the experience among surgeons in treating FNSF and identifying variables that play a role in the treatment algorithm for these patients. In addition, seven detailed, clinical vignettes were presented to further inquire on surgeon treatment preferences. Binomial distribution analysis was used to evaluate for common trends within the surgeon's treatment preferences. RESULTS: Seventy orthopedic surgeons completed the survey, the majority of whom were on active duty status in the U.S. Military (82.86%) and having under 5 years of experience (61.43%). Majority of surgeons elected for a multiple screw construct (92.86%), however the orientation of the multiple screws was dependent on whether the fracture was open or closed. Management for compression-sided FNSF involving ≥50% of the femoral neck width, tension-sided FNSF, and stress fractures demonstrating fracture line progression had consensus for operative management. Respondents agreed upon prophylactic fixation of the contralateral hip if the following factors were involved: Complete fracture (98.57%), compression-sided fracture line >75% (88.57%), compression-sided fracture line >50-75% with hip effusion (88.57%), contralateral tension-sided fracture (87.14%), and compression-sided fracture line >50-75% (84.29%). An FNSF < 50% on the contralateral femoral neck or a hip effusion was indeterminate in surgeons indicating need for prophylactic fixation. Majority of surgeons (77.1%) utilized restricted toe-touch weight-bearing for postoperative mobility restrictions. CONCLUSIONS: Consensus exists for surgical and non-surgical management of FNSF by U.S. military orthopedic surgeons, despite the preponderance of surgeons reporting a low annual volume of FNSF cases treated. However, there are certain aspects in the operative and non-operative management of FNSF that are unanimously adhered to. Specifically, our results demonstrate that there is no clear indication on the management of FNSF when an associated hip effusion is involved. Additionally, the indications for surgically treating contralateral FNSF are unclear. LEVEL OF EVIDENCE: IV.

Modified Clavien-Dindo-Sink Classification System for operative complications in adult spine surgery.

OBJECTIVE: Currently there is no standardized mechanism to describe or compare complications in adult spine surgery. Thus, the purpose of the present study was to modify and validate the Clavien-Dindo-Sink complication classification system for applications in spine surgery. METHODS: The Clavien-Dindo-Sink complication classification system was evaluated and modified for spine surgery by four fellowship-trained spine surgeons using a consensus process. A distinct group of three fellowship-trained spine surgeons completed a randomized electronic survey grading 71 real-life clinical case scenarios. The survey was repeated 2 weeks after its initial completion. Fleiss' and Cohen's kappa (κ) statistics were used to evaluate interrater and intrarater reliabilities, respectively. RESULTS: Overall, interobserver reliability during the first and second rounds of grading was excellent with a κ of 0.847 (95% CI 0.785-0.908) and 0.852 (95% CI 0.791-0.913), respectively. In the first round, interrater reliability ranged from good to excellent with a κ of 0.778 for grade I (95% CI 0.644-0.912), 0.698 for grade II (95% CI 0.564-0.832), 0.861 for grade III (95% CI 0.727-0.996), 0.845 for grade IV-A (95% CI 0.711-0.979), 0.962 for grade IV-B (95% CI 0.828-1.097), and 0.960 for grade V (95% CI 0.826-1.094). Intraobserver reliability testing for all three independent observers was excellent with a κ of 0.971 (95% CI 0.944-0.999) for rater 1, 0.963 (95% CI 0.926-1.001) for rater 2, and 0.926 (95% CI 0.869-0.982) for rater 3. CONCLUSIONS: The Modified Clavien-Dindo-Sink Classification System demonstrates excellent interrater and intrarater reliability in adult spine surgery cases. This system provides a useful framework to better communicate the severity of spine-related complications.

Multifaceted approach toward mapping out the anticancer properties of small molecules via in vitro evaluation on melanoma and nonmelanoma skin cancer cells, and in silico target fishing.

Melanoma and nonmelanoma skin cancers are among the most prevalent and most lethal forms of skin cancers. To identify new lead compounds with potential anticancer properties for further optimization, in vitro assays combined with in-silico target fishing and docking have been used to identify and further map out the antiproliferative and potential mode of action of molecules from a small library of compounds previously prepared in our laboratory. From screening these compounds in vitro against A375, SK-MEL-28, A431, and SCC-12 skin cancer cell lines, 35 displayed antiproliferative activities at the micromolar level, with the majority being primarily potent against the A431 and SCC-12 squamous carcinoma cell lines. The most active compounds 11 (A431: IC50 = 5.0 µM, SCC-12: IC50 = 2.9 µM, SKMEL-28: IC50 = 4.9 µM, A375: IC50 = 6.7 µM) and 13 (A431: IC50 = 5.0 µM, SCC-12: IC50 = 3.3 µM, SKMEL-28: IC50 = 13.8 µM, A375: IC50 = 17.1 µM), significantly and dose-dependently induced apoptosis of SCC-12 and SK-MEL-28 cells, as evidenced by the suppression of Bcl-2 and upregulation of Bax, cleaved caspase-3, caspase-9, and PARP protein expression levels. Both agents significantly reduced scratch wound healing, colony formation, and expression levels of deregulated cancer molecular targets including RSK/Akt/ERK1/2 and S6K1. In silico target prediction and docking studies using the SwissTargetPrediction web-based tool suggested that CDK8, CLK4, nuclear receptor ROR, tyrosine protein-kinase Fyn/LCK, ROCK1/2, and PARP, all of which are dysregulated in skin cancers, might be prospective targets for the two most active compounds. Further validation of these targets by western blot analyses, revealed that ROCK/Fyn and its associated Hedgehog (Hh) pathways were downregulated or modulated by the two lead compounds. In aggregate, these results provide a strong framework for further validation of the observed activities and the development of a more comprehensive structure-activity relationship through the preparation and biological evaluation of analogs.

Identification of optimal control compartments for serial near-infrared spectroscopy assessment of lower extremity compartmental perfusion.

Near-infrared spectroscopy (NIRS) has shown promise in detecting ischemic changes in acute compartment syndrome. The objectives of this study were to 1) assess the correlation in NIRS values between upper and lower extremity control sites for bilateral lower extremity trauma and 2) investigate the effect of skin pigmentation on NIRS values. Forty-four volunteers (14 male, 30 female) were monitored over separate 1-hour sessions. NIRS leads were placed over leg and upper extremity compartments. Colorimeters were used to document skin pigmentation. NIRS values between corresponding contralateral compartments were extremely well correlated (r = 0.76-0.90). Upper extremity NIRS values were correlated to leg values in the following order: volar (r = 0.65-0.71), dorsal (r = 0.36-0.60), and deltoid (r = 0.42-0.51). A negative correlation was observed between melanin and NIRS values. Analogous leg compartments are the optimal site of control for each other. The volar forearm may be the best upper extremity control. Skin pigmentation may affect absolute NIRS values.

Effects of the COVID-19 booster vaccine on glycemia and insulin resistance in people with type 1 diabetes: A prospective pilot study.

AIMS: Inflammation can trigger hyperglycemia in people with type 1 diabetes (T1D). Vaccines purposefully intend to cause an acute immunogenic response, and booster vaccines may cause even more potent immunologic responses. However, the effects of vaccines on glycemic control and insulin requirements in the days immediately post-vaccination remains poorly understood. The aim of this study was to examine the changes in glycemic control and insulin usage immediately preceding and following a COVID-19 booster vaccine among adults with T1D. METHODS: In this prospective cohort study of adults with T1D, participants wore blinded Dexcom G6 Pro continuous glucose monitors for 10 days. After a baseline period, participants received a COVID-19 booster vaccine, and subsequent changes in glycemic indices were evaluated. RESULTS: Among the 21 enrolled participants, 38% received a Moderna and 62% Pfizer-BioNTech booster. Compared to baseline (162.9 ± 44.1 mg/dL), mean glucose was significantly increased at Day 2 (172.8 ± 47.0 mg/dL; p = 0.04) and Day 3 (173.1 ± 45.0 mg/dL; p = 0.02) post-vaccination. Insulin resistance was also increased on Day 2 (p = 0.03). There were no differences in outcome metrics between booster vaccine manufacturers. CONCLUSIONS: These results suggest that adults with type 1 diabetes may experience transient mild glycemic elevations after receiving a COVID-19 booster vaccination. Studies examining the effects of other vaccines are warranted.

Clinicopathological characteristics and molecular analyses of multifocal intraductal papillary mucinous neoplasms of the pancreas.

OBJECTIVE: To examine the clinicopathologic features and clonal relationship of multifocal intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. BACKGROUND: Intraductal papillary mucinous neoplasms are increasingly diagnosed cystic precursor lesions of pancreatic cancer. Intraductal papillary mucinous neoplasms can be multifocal and a potential cause of recurrence after partial pancreatectomy. METHODS: Thirty four patients with histologically documented multifocal IPMNs were collected and their clinicopathologic features catalogued. In addition, thirty multifocal IPMNs arising in 13 patients from 3 hospitals were subjected to laser microdissection followed by KRAS pyrosequencing and loss of heterozygosity (LOH) analysis on chromosomes 6q and 17p. Finally, we sought to assess the clonal relationships among multifocal IPMNs. RESULTS: We identified 34 patients with histologically documented multifocal IPMNs. Synchronous IPMNs were present in 29 patients (85%), whereas 5 (15%) developed clinically significant metachronous IPMNs. Six patients (18%) had a history of familial pancreatic cancer. A majority of multifocal IPMNs (86% synchronous, 100% metachronous) were composed of branch duct lesions, and typically demonstrated a gastric-foveolar subtype epithelium with low or intermediate grades of dysplasia. Three synchronous IPMNs (10%) had an associated invasive cancer. Molecular analysis of multiple IPMNs from 13 patients demonstrated nonoverlapping KRAS gene mutations in 8 patients (62%) and discordant LOH profiles in 7 patients (54%); independent genetic alterations were established in 9 of the 13 patients (69%). CONCLUSIONS: The majority of multifocal IPMNs arise independently and exhibit a gastric-foveolar subtype, with low to intermediate dysplasia. These findings underscore the importance of life-long follow-up after resection for an IPMN.

Preparing the lumbar intervertebral disk space for interbody procedures: a comparison between the traditional method and a new automated method.

STUDY DESIGN: Cadaveric laboratory study. OBJECTIVE: To quantify and compare automated disk-space preparation with traditional methods. SUMMARY OF BACKGROUND DATA: Removal of nucleus pulposus to prepare a disk space for interbody fusion is performed with various techniques. Our aim was to determine the safety and effectiveness of an automated technique in comparison to traditional methods and gauge its expected clinical application. METHODS: This study was conducted in 2 phases. In the phase 1 safety trial, ''maximal'' force was applied to an automated shaver against cadaveric annulus and endplates until flexion of the shaft caused the blades to bind. This simulated the risk of creating an incidental cortical or annular defect. In phase 2, 27 cadaveric lumbar disk spaces were randomized to traditional or automated preparation techniques through a standard transforaminal lumbar interbody fusion approach. Traditional method comprised the use of paddle shavers, pituitary rongeurs, and curettes. Automated technique involved insertion of an 8-mm paddle shaver, followed by straight and angled hand pieces to remove nucleus pulposus and endplate cartilage. Unintended cortical and annular breaches, preparation time, instrument insertions, percentage area of exposed endplate underlying the nucleus pulposus, and percentage volume of nuclear space cleared were measured and compared. RESULTS: In phase 1, ''maximal'' force applied for 10 seconds produced no full-thickness annular or cortical defects. In phase 2, automated technique produced fewer endplate cortical defects (3 vs. 7) and full-thickness annular breaches (0 vs. 1), required fewer instrument insertions (29 vs. 6; P<0.001), exposed more endplate (65% vs. 52%; P=0.037), and removed more nucleus pulposus volume (83% vs. 59%; P=0.01). CONCLUSIONS: Automated shaving decreased instrument insertions and prepared the disk space more effectively, with fewer cortical or annular defects. This technique holds promise for improved outcomes in spinal fusion surgery.

Recurrence of a giant cell tumor of the hand after 42 years: case report.

Giant cell tumors of bone in the hand are rare. We present a case of a recurrent giant cell tumor in the metacarpal 42 years after intralesional excision and autogenous bone grafting. The possibility of recurrent disease should be considered in the evaluation of any patient presenting with new onset of pain at the site of a previously addressed giant cell tumor. Management of these recurrent lesions should include wide excision with digit salvaging procedures or ray amputation owing to the high rates of treatment failures seen with marginal excision.

Growth Hormone-Releasing Hormone in Endothelial Inflammation.

The discovery of hypothalamic hormones propelled exciting advances in pharmacotherapy and improved life quality worldwide. Growth hormone-releasing hormone (GHRH) is a crucial element in homeostasis maintenance, and regulates the release of growth hormone from the anterior pituitary gland. Accumulating evidence suggests that this neuropeptide can also promote malignancies, as well as inflammation. Our review is focused on the role of that 44 - amino acid peptide (GHRH) and its antagonists in inflammation and vascular function, summarizing recent findings in the corresponding field. Preclinical studies demonstrate the protective role of GHRH antagonists against endothelial barrier dysfunction, suggesting that the development of those peptides may lead to new therapies against pathologies related to vascular remodeling (eg, sepsis, acute respiratory distress syndrome). Targeted therapies for those diseases do not exist.

Pectoralis Major Tendon Tears During Airborne Operations: Are These Injuries Isolated?

INTRODUCTION: Pectoralis major tendon tears are an injury pattern often treated in military populations. Although the majority of pectoralis major tendon tears occur during eccentric loading as in bench press weightlifting, military service members may also experience this injury from a blunt injury and traction force produced by static line entanglement during airborne operations. Although these injuries rarely occur in isolation, associated injury patterns have not been investigated previously. MATERIALS AND METHODS: After obtaining institutional review board approval, medical records were reviewed for all patients who underwent surgical repair of a pectoralis major tendon tear sustained during static line parachuting at a single institution. Radiology imaging, operative notes, and outpatient medical records were examined to determine concomitant injury patterns for each patient identified over a 4-year study period. RESULTS: Twenty-five service members met the study inclusion criteria. All patients underwent presurgical magnetic resonance imaging. Of these 25 service members, 10 (40%) presented with a total of 13 concomitant injuries identified on physical exams or imaging studies. The most common associated injuries were injuries to the biceps brachii and a partial tear of the anterior deltoid. Biceps brachii injuries consisted of muscle contusion proximal long head tendon rupture, proximal short head tendon rupture, partial muscle laceration, and complete muscle transection. Additional concomitant injuries included transection of coracobrachialis, a partial tear of the inferior subscapularis tendon, antecubital fossa laceration, an avulsion fracture of the sublime tubercle, and an avulsion fracture of the coracoid process. CONCLUSIONS: Military static line airborne operations pose a unique risk of pectoralis major tendon tear. Unlike the more common bench press weightlifting tear mechanism, pectoralis major tendon tears associated with static line mechanism present with a concomitant injury in 40% of cases, with the most common associated injury occurring about the biceps brachii. Treating providers should have a high index of suspicion for concomitant injuries when treating pectoralis major tendon tears from this specific mechanism of injury.