59th Medical Wing

Although specific bacteria, dental plaque, and age are associated with periodontal disease, there are currently no reliable predictors of periodontitis severity. Studies in twins have suggested a genetic contribution to the pathogenesis of periodontitis, but previous attempts to identify genetic markers have been unsuccessful. The pro-inflammatory cytokines interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF alpha) are key regulators of the host responses to microbial infection. IL-1 is also a major modulator of extracellular matrix catabolism and bone resorption. We report a specific genotype of the polymorphic IL-1 gene cluster that was associated with severity of periodontitis in non-smokers, and distinguished individuals with severe periodontitis from those with mild disease (odds ratio 18.9 for ages 40-60 years). Functionally, the specific periodontitis-associated IL-1 genotype comprises a variant in the IL-1B gene that is associated with high levels of IL-1 production. In smokers severe disease was not correlated with genotype. In this study, 86.0% of the severe periodontitis patients were accounted for by either smoking or the IL-1 genotype. This study demonstrates that specific genetic markers, that have been associated with increased IL-1 production, are a strong indicator of susceptibility to severe periodontitis in adults.

Advances in prehospital care and trauma resuscitation have enabled the early survival of many injured patients who previously had a high chance of dying at the accident scene or en route to the hospital. The change in the spectrum of injury severity, characterized by high-energy blunt trauma with multiple-organ injury and fractures, and the emergence of semiautomatic handguns with multiple penetrating wounds, present new challenges to all surgeons. In conventional trauma care, definitive control and repair of all injuries may be accomplished in the immediate postinjury setting; however, the physiologic derangements of the massive shock state caused by the aforementioned injury patterns often lead to a fully repaired but dead patient. In response to these catastrophic challenges, the concept of “damage control” as a treatment merely to control but not definitively repair injuries has arisen. This term was originally coined by the United States Navy, in reference to “the capacity of a ship to absorb damage and maintain mission integrity.”1 In the patient with multiple injuries who is exsanguinating, this has been paraphrased to indicate the sum total of the maneuvers necessary to ensure patient survival above all else. 2 Definitive control of hemorrhage by pressure is not new to surgery. Pringle first enunciated the principles of compression and hepatic packing for control of portal venous hemorrhage in 1908. 3 This was modified by Halsted, who inserted rubber sheets between the liver and packs to protect hepatic parenchyma. 4 Military experience in World War II and Vietnam discouraged this practice. 5 As early as 1963, however, Shaftan et al. observed that to limit the mortality of liver injury, both faster and better resuscitation and better treatment of the wounds were necessary. 6 In 1979, Calne et al. described four cases in which massive exsanguinating hemorrhage from the liver was temporarily controlled with gauze packing, enabling safe transfer and definitive management at a more appropriate institution. 7 In 1983, Stone and associates popularized the technique of truncation of laparotomy, establishment of intra-abdominal pack tamponade, and then completion of definitive surgical repair later, once coagulation had returned to an acceptable level. This proved to be lifesaving in previously nonsalvageable situations. 8 Damage control, abbreviated laparotomy specifically to salvage trauma patients with exsanguination, was described at several institutions almost simultaneously in the early 1990s. 9–11 Rotondo et al. found a remarkable salvage rate of over 70% in a limited number of patients treated with damage control for abdominal vascular injury and massive shock, hypothermia, and acidosis. Since then, damage control has gained widespread use throughout North America, Israel, and South Africa. Recently, a review by Rotondo and Zonies identified 961 damage control patients in the literature, with 50% mortality and 40% morbidity overall. 12 Subsequent reports have expanded this list to over 1,000 patients (Table 1). Table 1: Cumulative Review of Damage ControlDamage control as currently practiced has three separate components. The first is abbreviated resuscitative surgery for rapid control of hemorrhage and contamination. This is obtained as quickly as possible in the operating room, but traditional repairs are deferred in favor of rapid measures that control hemorrhage, restore flow where needed, and control or contain contamination. Intra-abdominal packing and temporary abdominal closure complete this truncated first and critical step (Part I). The patient is then moved to the intensive care unit, where Part II consists of ongoing core rewarming, correction of coagulopathy, fluid resuscitation and optimization of hemodynamic status, as well as reexamination to diagnose all injuries. When normal physiology has been restored, reexploration is undertaken for definitive management of injuries and abdominal closure (Part III). 9,13 Increases in firearm violence present a new source of challenge to which damage control techniques are often applicable. In one study from the United States in an urban setting, firearm-related homicide increased by 123% over 5 years, and the number of victims who died at the scene rose from 5% to 34%. This was despite the designation of six trauma centers in that county, reflecting a shift toward high-velocity, high-caliber weaponry. 14 It has been apparent in our clinical practice for some time that inner city street weaponry and wounding patterns are changing, with multiple-shot injury patterns becoming much more common. These patients often present with multicavitary sites of exsanguination, and damage control techniques have assumed a prominent role in their initial management. This article reviews the principles of damage control as a series of linked surgical maneuvers, designed to address the physiologic abnormalities first, followed by a secondary resuscitative phase, and then the definitive surgical procedures themselves. Though damage control was traditionally described for massive abdominal trauma with vascular injury, recent applications in the chest and even to peripheral vascular injury have been reported. 15–17 GENERAL CONSIDERATIONS AND SECONDARY RESUSCITATION The goal of the damage control approach is to preserve the living patient. The triad of hypothermia, acidosis, and coagulopathy in the patient with multiple injuries is often lethal; Ferrara et al. reported 90% mortality in patients with these findings requiring massive transfusion. 18 Rewarming, replacement of coagulation factors, and fluid and blood resuscitation are critical to counter this state. 11 Damage control encompasses this algorithm, emphasizing rapid but definitive hemostasis, closing all hollow viscus injuries or performing only essential bowel resections, and delaying the more traditional or standard reconstruction until after the patient has been stabilized and all physiologic parameters have been corrected. Primary Operation and Hemorrhage Control The initial damage control laparotomy (Part I) includes five components: control of hemorrhage, exploration, control of contamination, definitive packing, and rapid abdominal closure. 19 An important distinction should be made between resuscitative and therapeutic packing. Resuscitative packing with manual compression of a bleeding site is often used as an initial short-term (minutes) measure to control or minimize blood loss while repairing other higher priority injuries or “catching up.”20 Therapeutic packing, in contrast, provides tamponade of bleeding when it is surgically unmanageable or a coagulopathy has developed. This is used to enable a longer period of resuscitation, to give the body time to correct the metabolic derangements mentioned above, 21 and to access other means of definitive vascular control such as therapeutic angiography. The decision to truncate the procedure should be made early when, in the judgment of the surgeon, definitive repair is either likely to exceed the patient’s physiologic reserve or is technically impossible. 22 The indications for damage control have recently been described in six general categories (Table 2). 23 Critical variables include the surgeon’s ability to control hemorrhage, the severity of the injuries, and the presence of other associated injuries. Packing as a therapeutic procedure should be implemented well before massive blood loss (10–15 units of packed red blood cells) has occurred. 24,25 Other variables that have been identified as significant include severe injury (Injury Severity Score >35), hypotension (shock in excess of 70 minutes), hypothermia (temperature <34°C), coagulopathy (prothrombin time >19 seconds or partial thromboplastin time >60 seconds), and acidosis (pH <7.2). 5,26,27 With these caveats, the need for packing as a planned therapeutic approach can often be anticipated preoperatively. Packing does not take the place of vessel ligation or clamping. Most vessels can be rapidly isolated, repaired, ligated, or shunted if necessary. Once definitive vascular control is obtained, packing of all raw or dissected surfaces is done. Occasionally, with injury to the liver, pelvis, or large muscle beds, packing must be done and prompt angiography performed to control these intraparenchymal or intramuscular vessels. Regardless of the bleeding source, expeditious vascular control is of paramount importance. Without it, exsanguination is ensured. Table 2: Indications for the Damage Control ApproachHypothermia, Acidosis, and Coagulopathy: The Lethal Triad Hypothermia Thermal homeostasis depends on a balance between the factors governing heat loss—conduction, convection, evaporation, and radiation—and the body’s ability to generate and maintain metabolic energy. Heat loss begins at the moment of traumatic insult, and is exacerbated by extenuating circumstances such as shock and low perfusion, prolonged exposure, immobility of the acutely injured patient, and extremes of age. In the absence of a preemptive treatment approach, this process continues in the emergency department, where the patient is unclothed and left fully exposed, with a resultant patient–room temperature gradient of 15°C. In this setting, measurable temperature loss occurs in up to 92% of patients. 28,29 Clinically significant hypothermia is considered present when the core temperature is less than 35°C, 30 and temperature less than 34°C has been linked with a need for early therapeutic packing. 27 Hypothermia has been reported in 21% of all severely injured patients, and up to 46% of trauma victims requiring laparotomy leave the operating room hypothermic. 29,31 Clinically, hypothermic patients have significantly greater fluid, transfusion, vasopressor and inotropic requirements, resulting in higher incidences of organ dysfunction, mortality, and markedly prolonged intensive care unit stay. 31–35 Hypothermia itself may not be the cause of these conditions, but it reflects the magnitude of the original injury and the associated shock state. Passive external rewarming techniques include patient shivering and simple covering of the patient to minimize convective heat loss. Active external rewarming techniques include fluid-circulating heating blankets, convective warm air blankets, and radiant warmers. Paradoxically, the initial response to these techniques may be adverse, as fluid shifts and changes in vascular tone decrease venous return, lower blood pressure, and diminish cardiac output. The return of cold, acidotic blood to the central circulation may initially lower core temperature, and has been associated with ventricular fibrillation during rewarming. 36,37 Active core rewarming techniques include warmed airway gases, heated peritoneal or pleural lavage, warmed intravenous fluid infusion, and extracorporeal rewarming. Cold (i.e., room temperature) intravenous fluid administration has been invoked as the fastest way of accelerating hypothermia. 28 Countercurrent heat exchange mechanisms have enabled the rapid infusion of warmed banked blood products. 38 Extracorporeal rewarming techniques may be limited by the need for anticoagulation. Continuous arteriovenous rewarming, however, can be accomplished with a heparin-bonded circuit without a pump that may eliminate this limitation. This process is driven by the patient’s blood pressure; hence, its effectiveness is limited by hypotension. This technique can accomplish rewarming at a rate of 4° to 5°C per hour, which is far more efficient than the 1° to 2°C possible with other methods. Because warmed blood is sent directly to core organs, continuous arteriovenous rewarming rapidly increases core temperature by nonshivering thermogenesis, which may increase metabolic effectiveness. 36 Acidosis Acidosis associated with hypovolemic shock contributes to coagulopathic bleeding, which worsens the shock state. Correction requires not only control of hemorrhage but also optimization of oxygen delivery, blood and of cardiac output. a of resuscitative have been that conventional and venous oxygen and of coagulation factors and by fluid resuscitation, total and hypothermia, the severity of injury, shock, and metabolic acidosis may all to the of normal The clinical of coagulopathy is not by that other than the of factors and the number and of may be in the of Hypothermia in the patient to of and coagulation of the of these is by of and partial thromboplastin in hypothermic conditions, even where coagulation factors are to be is performed at than at the patient’s core temperature, and may the of in hypothermia to prolonged bleeding from a in in by temperature may also the and of despite the replacement of is often between and bleeding in patients who have massive transfusion, and the presence of hemorrhage in this is an for even with a in hypothermic has been to the of in the and of may also lead to is a simple that can coagulation abnormalities and give and that is not from coagulation the of with the coagulation from initial and to It is for use in the operating room, the of coagulopathy, and may be an early of the need for in patients with blunt of the damage control approach to coagulopathic bleeding have been an initial by et al. in in mortality with et al. have reported high survival damage control Subsequent reports have described both in a of trauma patients (i.e., and in general surgery patients. and the Increases in intra-abdominal pressure may circulation and organ perfusion, the and This can from abdominal trauma by or the use of abdominal return is by compression and of and lower In increased abdominal pressure, associated and a increase in all to diminish cardiac output. blood flow to the liver, and may all be and to the of may also from compression of the can vascular and this from increased abdominal pressure with resultant in and worsens Paradoxically, in this may with of the and of this is the of this but is well described in the surgical 70 packing as a damage control procedure can be a cause of significant abdominal with compression of the to In this setting, a patient should be returned to the operating room for of if of some of the laparotomy to decrease intra-abdominal pressure and to in perfusion, cardiac and In the absence of this packs should be left in place until the patient’s hemodynamic has acidosis has and coagulopathy has been corrected. In this should be accomplished to of the initial packing. may be appropriate if was initially as this may the of a for injury should be is and abdominal closure should be performed if has to this without CONSIDERATIONS The of for rapid abdominal in the trauma patient is made in one from process to In the presence of severe the initially to above the may be In our experience with patients with a access to the can be gained a approach, to and of and bowel from the of the The initial maneuvers on the should be rapid but and are quickly of the abdominal is performed to enable multiple laparotomy packing. This initial packing of the sites of bleeding, from vascular in penetrating injury, or liver in blunt bleeding is less common. this a large abdominal is to abdominal and to all on the surgical bleeding controlled with the packing or during initial exploration, an injury was found and controlled with or this is an time to the to with and source of bleeding has been then a vascular injury is a likely source, and should be by more The bowel is and the are to the and their or the surgical This is important in penetrating pack from the sites of injury, and 19 Control of hemorrhage is the and is accomplished by repair or ligation of vessels. Critical such as the or can be shunted for temporary of can be simple or vascular between tamponade of vascular and viscus injuries has been but in our experience is less applicable. may be necessary for completion of control and temporary for this is high abdominal or or tamponade as a temporary measure to increase blood viscus injury must be controlled as to limit and may be accomplished with or without Occasionally, the injured bowel with or is to contain temporary control of hemorrhage and is obtained, the decision to with definitive repair must be made in with the In the of hypothermia, acidosis, prolonged shock, or coagulopathy, the procedure should be truncated and the patient to the intensive care unit for The presence and of injuries must be when the patient’s physiologic the more injured patient with more severe requires less to be done at this initial are the for damage control packing, and should be to three pressure bleeding, pressure should and should be have as have described the use of or as an between and packing to pack at but have not found these to be necessary. closure of the packed is accomplished by rapid closure the the of abdominal and the and The massive associated with fluid resuscitation and in these patients may even closure impossible. of a or intravenous fluid to has been described as a temporary in this have described to the to preserve the for closure use only the is to or use the for temporary closure. use a modified approach by an surgical over the of the abdominal with its the are above the and the and at the of the An is over the and and to the of the and while the abdominal are toward the The of to the abdominal fluid to the and a to the the has been described as a with the damage control approach, have had such in our this The of are definitive organ repair and complete closure. The should be undertaken when the patient is with correction of hypothermia, acidosis, and may be necessary if is of ongoing hemorrhage than units of packed red blood in the early acidosis, or abdominal massive may limit abdominal closure at but closure has been described in over of of is essential at and access should be the safe use of in an has been this is not our have or in the patient be of our experience that of the abdominal may at closure or of is limited to cases in which is other for of to initially with total and reserve until a can be in the patient. of a damage control may be appropriate for to to for of fluid and at closure. at this the be but the a large is with planned repair to 12 and be a abdominal reconstruction is with the of an closure. to 3 is for of a 6 to 12 this from the and closure can be requiring muscle the physiologic of the patient who requires the damage control approach, it is not that the rate of and mortality is includes intra-abdominal and abdominal organ is described in to of patients, significantly to the mortality rate of to In patients laparotomy for hepatic injury, of have been to to control liver bleeding include ligation of bleeding partial and hepatic tamponade and have also been packing or tamponade is an procedure to control The need for this approach has been reported in to 5% of liver injuries. be the packs must pressure and that are bleeding are not to control by The is injured in abdominal trauma and may present as a source of The patient in with injury requires immediate and at are and 19 Occasionally, the temporary packing to tamponade of vessels until coagulopathy is at the packs are and are at the surgeon’s and injuries to the and are often associated with vascular injury in the patient in mortality is to The should be the and of injury The should then be and Definitive repair is undertaken at and may include or more injury in the exsanguinating patient is with by rapid if a normal is in the of other severe injuries should be packed than to more bleeding and An however, ongoing hemorrhage from an and for In some for hemorrhage or may be more appropriate and than injuries are to reconstruction in the patient both bleeding is and temporary control of can be with can be injury in the patient can also be temporarily with a or Definitive repair can be accomplished at and are to the management of the severely injured patient with can restore of the in fractures, and venous bleeding is with by When laparotomy the of the of is to pack the with gauze to tamponade, the laparotomy, and directly to angiography for to control In our these cases are and closure has been necessary to limit the of and with and temporary at sites more conventional to in the patient in in the can be accomplished with temporary if injury is ligation should be considered as an and may be should be performed in the of In the time and blood should be the way to temporary closure and after physiologic Packing the when severely injured has physiologic and is limited to the and The goal of abbreviated is to bleeding and restore a physiologic state. of the can often rapidly and control of air may be an way to control hemorrhage in penetrating The the is between or with a vessel and control of air This the need for injury can be treated with airway control at the site of injuries, may be but can be to with with an can be repairs are not in the patient in and rapid of the or is injury is treated by and injury to control hemorrhage and maintain flow to repair and are rapid such as and at are time to use in the cold, exsanguinating patient. vascular control tamponade the site has been injury in the is for the patient in Most and can be to the patient’s (Table of the or or external however, often significant damage or This should be for the of situations. must be to lower and laparotomy to An to ligation may be the rapid of temporary or venous and is for time and blood performing reconstruction in the patient in must ligation to The damage control approach can be in operating room by general surgeons. the first of laparotomy or with control of bleeding and contamination, packing, and closure is for where experience with these injuries may be or the necessary for resuscitation may be Once Part is the patient can be to a trauma or with and in the patient management and definitive repair of the injuries. Damage control is of as a lifesaving in patients with exsanguinating trauma and intra-abdominal injuries. The technique can be in a of injury and is appropriate in patients acidosis, hypothermia, and coagulopathy from The resuscitation is at normal physiology and oxygen coagulopathy, hypothermia, and acidosis. of abdominal must be to The and pack is the time to definitive repair and and to place closure with or without must be done with on the and the of the from several up to of patients this approach, the of intra-abdominal and organ are study is to more better for this is also to the of to of resuscitation, better of temporary and to limit intra-abdominal and or blunt organ and The use of procedures and the of the damage control approach of surgical for injuries

Pest and pathogen losses jeopardise global food security and ever since the 19(th) century Irish famine, potato late blight has exemplified this threat. The causal oomycete pathogen, Phytophthora infestans, undergoes major population shifts in agricultural systems via the successive emergence and migration of asexual lineages. The phenotypic and genotypic bases of these selective sweeps are largely unknown but management strategies need to adapt to reflect the changing pathogen population. Here, we used molecular markers to document the emergence of a lineage, termed 13_A2, in the European P. infestans population, and its rapid displacement of other lineages to exceed 75% of the pathogen population across Great Britain in less than three years. We show that isolates of the 13_A2 lineage are among the most aggressive on cultivated potatoes, outcompete other aggressive lineages in the field, and overcome previously effective forms of plant host resistance. Genome analyses of a 13_A2 isolate revealed extensive genetic and expression polymorphisms particularly in effector genes. Copy number variations, gene gains and losses, amino-acid replacements and changes in expression patterns of disease effector genes within the 13_A2 isolate likely contribute to enhanced virulence and aggressiveness to drive this population displacement. Importantly, 13_A2 isolates carry intact and in planta induced Avrblb1, Avrblb2 and Avrvnt1 effector genes that trigger resistance in potato lines carrying the corresponding R immune receptor genes Rpi-blb1, Rpi-blb2, and Rpi-vnt1.1. These findings point towards a strategy for deploying genetic resistance to mitigate the impact of the 13_A2 lineage and illustrate how pathogen population monitoring, combined with genome analysis, informs the management of devastating disease epidemics.

BACKGROUND: Current clinical practice guidelines (CPGs) for posttraumatic stress disorder (PTSD) offer contradictory recommendations regarding use of medications or psychotherapy as first-line treatment. Direct head-to-head comparisons are lacking. METHODS: Systemic review of Medline, EMBASE, PILOTS, Cochrane Central Register of Controlled Trials, PsycINFO, and Global Health Library was conducted without language restrictions. Randomized clinical trials ≥8 weeks in duration using structured clinical interview-based outcome measures, active-control conditions (e.g. supportive psychotherapy), and intent-to-treat analysis were selected for analyses. Independent review, data abstraction, and bias assessment were performed using standardized processes. Study outcomes were grouped around conventional follow-up time periods (3, 6, and 9 months). Combined effect sizes were computed using meta-analyses for medication versus control, medication pre-/posttreatment, psychotherapy versus control, and psychotherapy pre-/posttreatment. RESULTS: Effect sizes for trauma-focused psychotherapies (TFPs) versus active control conditions were greater than medications versus placebo and other psychotherapies versus active controls. TFPs resulted in greater sustained benefit over time than medications. Sertraline, venlafaxine, and nefazodone outperformed other medications, although potential for methodological biases were high. Improvement following paroxetine and fluoxetine treatment was small. Venlafaxine and stress inoculation training (SIT) demonstrated large initial effects that decreased over time. Bupropion, citalopram, divalproex, mirtazapine, tiagabine, and topiramate failed to differentiate from placebo. Aripiprazole, divalproex, guanfacine, and olanzapine failed to differentiate from placebo when combined with an antidepressant. CONCLUSIONS: Study findings support use of TFPs over nontrauma-focused psychotherapy or medication as first-line interventions. Second-line interventions include SIT, and potentially sertraline or venlafaxine, rather than entire classes of medication, such as SSRIs. Future revisions of CPGs should prioritize studies that utilize active controls over waitlist or treatment-as-usual conditions. Direct head-to-head trials of TFPs versus sertraline or venlafaxine are needed.

Emerging zoonoses threaten global health, yet the processes by which they emerge are complex and poorly understood. Nipah virus (NiV) is an important threat owing to its broad host and geographical range, high case fatality, potential for human-to-human transmission and lack of effective prevention or therapies. Here, we investigate the origin of the first identified outbreak of NiV encephalitis in Malaysia and Singapore. We analyse data on livestock production from the index site (a commercial pig farm in Malaysia) prior to and during the outbreak, on Malaysian agricultural production, and from surveys of NiV's wildlife reservoir (flying foxes). Our analyses suggest that repeated introduction of NiV from wildlife changed infection dynamics in pigs. Initial viral introduction produced an explosive epizootic that drove itself to extinction but primed the population for enzootic persistence upon reintroduction of the virus. The resultant within-farm persistence permitted regional spread and increased the number of human infections. This study refutes an earlier hypothesis that anomalous El Niño Southern Oscillation-related climatic conditions drove emergence and suggests that priming for persistence drove the emergence of a novel zoonotic pathogen. Thus, we provide empirical evidence for a causative mechanism previously proposed as a precursor to widespread infection with H5N1 avian influenza and other emerging pathogens.

BACKGROUND: Whether video laryngoscopy as compared with direct laryngoscopy increases the likelihood of successful tracheal intubation on the first attempt among critically ill adults is uncertain. METHODS: In a multicenter, randomized trial conducted at 17 emergency departments and intensive care units (ICUs), we randomly assigned critically ill adults undergoing tracheal intubation to the video-laryngoscope group or the direct-laryngoscope group. The primary outcome was successful intubation on the first attempt. The secondary outcome was the occurrence of severe complications during intubation; severe complications were defined as severe hypoxemia, severe hypotension, new or increased vasopressor use, cardiac arrest, or death. RESULTS: The trial was stopped for efficacy at the time of the single preplanned interim analysis. Among 1417 patients who were included in the final analysis (91.5% of whom underwent intubation that was performed by an emergency medicine resident or a critical care fellow), successful intubation on the first attempt occurred in 600 of the 705 patients (85.1%) in the video-laryngoscope group and in 504 of the 712 patients (70.8%) in the direct-laryngoscope group (absolute risk difference, 14.3 percentage points; 95% confidence interval [CI], 9.9 to 18.7; P<0.001). A total of 151 patients (21.4%) in the video-laryngoscope group and 149 patients (20.9%) in the direct-laryngoscope group had a severe complication during intubation (absolute risk difference, 0.5 percentage points; 95% CI, -3.9 to 4.9). Safety outcomes, including esophageal intubation, injury to the teeth, and aspiration, were similar in the two groups. CONCLUSIONS: Among critically ill adults undergoing tracheal intubation in an emergency department or ICU, the use of a video laryngoscope resulted in a higher incidence of successful intubation on the first attempt than the use of a direct laryngoscope. (Funded by the U.S. Department of Defense; DEVICE ClinicalTrials.gov number, NCT05239195.).

Previous analyses regarding effects of periodontal treatment on glycemic control included studies where causal association might not be assumed, or the results were reported non-quantitatively. We initiated this meta-analysis of 10 intervention studies to quantify the effects of periodontal treatment on HbA1c level among diabetic patients, to explore possible causes for the discrepant reports, and to make recommendations for future studies. Data sources were MEDLINE (January, 1980, to January, 2005), the EBMR, Cochrane Register, and bibliographies of the published articles. Three investigators extracted data regarding intervention, outcomes, and effect size. A total of 456 patients was included in this analysis, with periodontal treatment as predictor and the actual change in hemoglobin A1c level as the outcome. The weighted average decrease in actual HbA1c level was 0.38% for all studies, 0.66% when restricted to type 2 diabetic patients, and 0.71% if antibiotics were given to them. However, none was statistically significant.

BACKGROUND: Currently, there is little information available on the treatment and outcome of intraoperative periprosthetic humeral fractures that occur during shoulder arthroplasty. The purpose of this study was to report on the incidence, treatment, and outcome of, as well as the risk factors for, intraoperative periprosthetic humeral fractures. METHODS: Between 1980 and 2002, forty-five intraoperative periprosthetic humeral fractures occurred during shoulder arthroplasty at our institution. Twenty-eight fractures occurred during primary total shoulder arthroplasty, three occurred during primary hemiarthroplasty, and fourteen occurred during revision arthroplasty. Nineteen fractures involved the greater tuberosity, sixteen involved the humeral shaft, six involved the metaphysis, three involved the greater tuberosity and the humeral shaft, and one involved both the greater and lesser tuberosities. All patients were followed for a minimum of two years. At the time of the latest follow-up, outcomes were assessed, radiographs were examined, and relative risks were calculated. RESULTS: Over the twenty-two-year study period, the rate of intraoperative humeral fractures at our institution was 1.5%. All fractures healed at a mean of seventeen weeks. In the primary arthroplasty group (thirty-one patients), range of motion and pain scores improved significantly (p < 0.05) at the time of follow-up. In the revision arthroplasty group (fourteen patients), range of motion remained unchanged whereas pain scores improved significantly (p < 0.005). Transient nerve injuries occurred in six patients. Four fractures displaced postoperatively and were then treated nonoperatively; all four healed. Significant relative risks for intraoperative fracture were female sex, revision surgery, and press-fit implants (p < 0.05). CONCLUSIONS: The data from the present study suggest that although intraoperative humeral fractures are associated with a high rate of healing, there was a substantial rate of associated complications, including transient nerve injuries and fracture displacement. Significant risk factors for intraoperative fractures include female sex, revision surgery, and press-fit humeral implants.

BACKGROUND: Knowledge of the influence of age on laryngeal dimensions is essential for all practitioners whose interest is the pediatric airway. Early cadaver studies documented that the larynx is conically shaped, with the apex of the cone caudally positioned at the nondistensible cricoid cartilage. These dimensions change during childhood, as the larynx assumes a more cylindrical shape. The authors analyzed laryngeal dimensions during development to determine if this relationship continues in unparalyzed children in whom laryngeal muscles are tonically active. The authors determined the relationships between the vocal cord, sub-vocal cord, and cricoid ring dimensions and the influence of age on these relationships. METHODS: Infants and children undergoing magnetic resonance imaging with propofol sedation had determinations of the transverse and anterior-posterior (AP) dimensions of the larynx at the most cephalad level of the larynx (vocal cords) and the most caudad level (cricoid). Most patients had an additional measurement (sub-vocal cord) at a level between the vocal cords and the cricoid ring. Relationships were obtained by plotting age against laryngeal dimensions and the ratio of laryngeal dimensions at different levels within the larynx. RESULTS: The authors measured transverse and AP laryngeal dimensions in 99 children, aged 2 months-13 yr. The relationship between the transverse and AP dimensions at all levels of the larynx did not change during development. Transverse and AP dimensions increased linearly with age at all levels of the larynx. In all children studied, the narrowest portion of the larynx was the transverse dimension at the level of the vocal cords. Transverse dimensions increased linearly in a caudad direction through the larynx ( P< 0.001), while AP dimensions did not change relative to laryngeal level. The shape of the cricoid ring did not change throughout childhood. CONCLUSIONS: In sedated, unparalyzed children, the narrowest portions of the larynx are the glottic opening (vocal cord level) and the immediate sub-vocal cord level, and there is no change in the relationships of these dimensions relative to cricoid dimensions throughout childhood.

OBJECTIVE: To determine whether transition from tube to all oral feeding can be accelerated by the early introduction of oral feeding in preterm infants. It is hypothesized that this shortened transition time will lead to earlier attainment of all oral feeding. DESIGN: Twenty-nine infants (<30 weeks' gestation) were randomized to an intervention or control group. The intervention group (n = 13) was initiated to oral feeding 48 hours after achieving full tube feeding (120 kcal/kg/d), and the feeding progression followed a structured protocol. The oral feeding management of the control infants (n = 16) was left to the discretion of their attending physicians. Oral feeding progress was monitored for achievement of selected feeding milestones: achievement of first and all successful oral feedings. Feeding performance was assessed by overall transfer (percent volume transferred during a feeding/total volume offered) and rate of milk transfer (mL/min), which were measured from introduction of oral feeding to first successful oral feeding. RESULTS: Infants in the experimental group, when compared with their control counterparts, were introduced to oral feeding significantly earlier (31.1 +/- 1.3 vs 33.7 +/- 0.9 weeks' postmenstrual age, respectively) and attained all oral feeding significantly earlier as well (34.5 +/- 1.6 vs 36.0 +/- 1.5 weeks' postmenstrual age, respectively). The transition time from full tube feeding to all oral feeding was 26.8 +/- 12.3 days for the experimental group and 38.4 +/- 14.0 days for the control group. Both groups of infants demonstrated similar increase in overall transfer and rate of milk transfer from introduction of oral feeding until achievement of first successful oral feeding. CONCLUSIONS: Early introduction of oral feeding accelerates the transition time from tube to all oral feeding. This not only allows earlier attainment of all oral feeding, but it also provides practice opportunities that enhance the oral motor skills necessary for safe and successful feeding.

In studies of wild animals, one frequently encounters both count and mark-recapture-recovery data. Here, we consider an integrated Bayesian analysis of ring¿recovery and count data using a state-space model. We then impose a Leslie-matrix-based model on the true population counts describing the natural birth-death and age transition processes. We focus upon the analysis of both count and recovery data collected on British lapwings (Vanellus vanellus) combined with records of the number of frost days each winter. We demonstrate how the combined analysis of these data provides a more robust inferential framework and discuss how the Bayesian approach using MCMC allows us to remove the potentially restrictive normality assumptions commonly assumed for analyses of this sort. It is shown how WinBUGS may be used to perform the Bayesian analysis. WinBUGS code is provided and its performance is critically discussed.

In order to investigate the prevalence of tick-borne infectious agents among ticks, ticks comprising five species from two genera (Hemaphysalis spp. and Ixodes spp.) were screened using molecular techniques. Ticks (3,135) were collected from small wild-caught mammals or by dragging/flagging in the Republic of Korea (ROK) and were pooled into a total of 1,638 samples (1 to 27 ticks per pool). From the 1,638 tick samples, species-specific fragments of Anaplasma phagocytophilum (1 sample), Anaplasma platys (52 samples), Ehrlichia chaffeensis (29 samples), Ehrlichia ewingii (2 samples), Ehrlichia canis (18 samples), and Rickettsia rickettsii (28 samples) were amplified by PCR assay. Twenty-one pooled and individual tick samples had mixed infections of two (15 samples) or three (6 samples) pathogens. In addition, 424 spleen samples from small captured mammals (389 rodents, 33 insectivores, and 2 weasels) were screened for selected zoonotic pathogens. Species-specific DNA fragments of A. phagocytophilum (110 samples), A. platys (68 samples), E. chaffeensis (8 samples), E. ewingii (26 samples), E. canis (51 samples), and Rickettsia sp. (22 samples) were amplified by PCR assay. One hundred thirty small mammals had single infections, while 4, 14, and 21 striped field mice (Apodemus agrarius) had mixed infections of four, three, and two pathogens, respectively. Phylogenetic analysis based on nucleotide sequence comparison also revealed that Korean strains of E. chaffeensis clustered closely with those from China and the United States, while the Rickettsia (rOmpA) sequences clustered within a clade together with a Chinese strain. These results suggest that these agents should be considered in differential diagnosis while examining cases of acute febrile illnesses in humans as well as animals in the ROK.

Thirty-five cases of Babesia gibsoni infection and 11 cases of Babesia canis infection were diagnosed and treated in dogs at Kadena Air Base in Okinawa, Japan, between April 1979 and February 1980. Diagnosis was made by demonstrating the organisms in blood smears and by serologic examination, using an indirect fluorescent antibody test. Serologic findings correlated well with the occurrence of infection in mature dogs, but poorly in young (1- to 3-month-old) dogs. Although these 2 intraerythrocytic parasites were readily distinguishable on Giemsa-stained blood smears and by the indirect fluorescent antibody test, the clinical syndromes were similar. Most dogs were anorectic and depressed and were found to have regenerative anemia. Of 37 dogs tested, 31 were Coomb's test-positive, and most of these became Coombs' test-negative after treatment and disappearance of clinical signs. Specific treatment consisted predominantly of the use of diminazene aceturate. Pentamidine isethionate also used. Although these drugs were effective in halting and reversing the clinical progression of the disease, they usually were ineffective in clearing the blood of B gibsoni organisms, and relapses commonly occurred. Both drugs appeared to be more effective against B canis. It was concluded that some of the several hundred dogs arriving in the United States annually from Okinawa are carriers of B gibsoni, a parasite only recently discovered in North America.

STUDY DESIGN: Systematic review of the literature. OBJECTIVES: To develop a grading scale to judge the quality of randomized clinical trials (RCTs) and conduct a systematic review of the published RCTs that assess nonoperative treatments for patellofemoral pain syndrome (PFPS). BACKGROUND: Systematic reviews of the quality and usefulness of clinical trials allow for efficient synthesis and dissemination of the literature, which should facilitate clinicians' efforts to incorporate principles of evidence-based practice in the clinical decision-making process. METHODS AND MEASURES: Using a scale based on criteria in the Cochrane Collaboration Handbook, we sought to critically appraise the methodology used in RCTs related to the nonoperative management of PFPS, synthesize and interpret our results, and report our findings in a user-friendly fashion. A scale to assess the methodological quality of trials was designed and pilot tested for its content and reliability. Published RCTs identified during a literature search were then selected and rated by 6 raters. We used predefined cutoff scores to identify specific weaknesses in the clinical research process that need to be improved in future clinical trials. RESULTS: The quality scale we developed was demonstrated to be sufficiently reliable to warrant interpretation of the reviewers' findings. The percentage of trials that met a minimum level of quality for each specific criterion ranged from a low of 25% for the adequacy of the description of the randomization procedure to a high of 95% for the description and standardization of the intervention. CONCLUSIONS: Based on the results of trials exhibiting a sufficient level of quality, treatments that were effective in decreasing pain and improving function in patients with PFPS were acupuncture, quadriceps strengthening, the use of a resistive brace, and the combination of exercises with patellar taping and biofeedback. The use of soft foot orthotics in patients with excessive foot pronation appeared useful in decreasing pain. In addition, at a short-term follow-up, patients who received exercise programs were discharged earlier from physical therapy. Unfortunately, most RCTs reviewed contained qualitative flaws that bring the validity of the results into question, thus diminishing the ability to generalize the results to clinical practice. These flaws were primarily in the areas of randomization procedures, duration of follow-up, control of cointerventions, assurance of blinding, accountability and proper analysis of dropouts, number of subjects, and the relevance of outcomes. Also, given the limited number of high-quality clinical trials, recommendations about supporting or refuting specific treatment approaches may be premature and can only be made with caution.

In Brief Objective: The objective of this study is to characterize modern point-of-injury (POI) en-route care platforms and to compare mortality among casualties evacuated with conventional military retrieval (CMR) methods to those evacuated with an advanced medical retrieval (AMR) capability. Background: Following a decade of war in Afghanistan, the impact of en-route care capabilities from the POI on mortality is unknown. Methods: Casualties evacuated from POI to one level III facility in Afghanistan (July 2008–March 2012) were identified from UK and US trauma registries. Groups comprised those evacuated by a medically qualified provider-led, AMR and those by a medic-led CMR capability. Outcomes were compared per incremental Injury Severity Score (ISS) bins. Results: Most casualties (n = 1054; 61.2%) were in the low-ISS (1–15) bracket in which there was no difference in en-route care time or mortality between AMR and CMR. Casualties in the mid-ISS bracket (16–50) (n = 583; 33.4%) experienced the same median en-route care time (minutes) on AMR and CMR platforms [78 (58) vs 75 (93); P = 0.542] although those on AMR had shorter time to operation [110 (95) vs 117 (126); P < 0.001]. In this mid-ISS bracket, mortality was lower in the AMR than in the CMR group (12.2% vs 18.2%; P = 0.035). In the high-ISS category (51–75) (n = 75; 4.6%), time to operation was lower in the AMR than the CMR group (66 ± 77 vs 113 ± 122; P = 0.013) but there was no difference in mortality. Conclusions: This study characterizes en-route care capabilities from POI in modern combat. Conventional platforms are effective in most casualties with low injury severity. However, a definable injury severity exists for which evacuation with an AMR capability is associated with improved survival. The greatest opportunity to improve the survivability of wartime injury exists in the prehospital setting. This study examines US and UK point-of-injury en-route care capabilities aboard distinct rotary wing platforms in southern Afghanistan. Severely injured casualties evacuated aboard an advanced medical retrieval platform were associated with a lower mortality.

Noncompressible torso hemorrhage is a leading cause of death in trauma, with many patients dying before definitive hemorrhage control. Resuscitative endovascular balloon occlusion of the aorta (REBOA) is an adjunct than can be used to expand the window of salvage in patients with end-stage hemorrhagic shock. The aim of this study was to evaluate the effect of continuous and intermittent REBOA (iREBOA) on mortality using a highly lethal porcine model of noncompressible torso hemorrhage. Male splenectomized pigs (70-90 kg) underwent a laparoscopic liver injury (80% resection of left lobe) followed by a 10-min free-bleed period. Animals were then divided into three groups (n = 8) for a 60-min intervention phase (n = 8): continuous occlusion (cREBOA), iREBOA, or no occlusion (nREBOA). Groups then underwent whole blood resuscitation, damage control surgery, and further critical care. Endpoints were mortality and hemodynamic and circulating measures of shock and resuscitation. Systolic blood pressure (in mmHg) at the end of the free-bleed period for cREBOA, iREBOA, and nREBOA was 31 ± 14, 48 ± 28, and 28 ± 17, respectively (P = 0.125). Following the start of the intervention phase, systolic blood pressure was higher in the iREBOA and cREBOA groups compared with the nREBOA (85 ± 37 and 96 ± 20 vs. 42 ± 4; P < 0.001). Overall mortality for the cREBOA, iREBOA, and nREBOA groups was 25.0%, 37.5%, and 100.0% (P = 0.001). Resuscitative endovascular balloon occlusion of the aorta can temporize exsanguinating hemorrhage and restore life-sustaining perfusion, bridging critical physiology to definitive hemorrhage control. Prospective observational studies of REBOA as a hemorrhage control adjunct should be undertaken in appropriate groups of human trauma patients.

Investigation of the efficacy of pharmacologic agents affecting myocardial infarct size after coronary artery occlusion is complicated by the variability of collateral flow among experimental animals which results in variability of infarct size. To overcome this difficulty, we developed an autoradiographic method to delineate the ischemic area at risk of necrosis after coronary artery occlusion and we invetigated the potential protective effect of a calcium antagonist verapamil. The left anterior descending coronary arteries of 25 barbiturate-anesthetized dogs were occluded. Thirty minutes later, highly radioactive human albumin microspheres labeled with 99mTc were injected into the left atrium. One hour after coronary artery occlusion, dogs were randomized to control or treated groups; the latter received a 0.2 mg/kg loading dose and 0.6 mg/kg per hr maintenance dose of verapamil intravenously. Eight hours after coronary artery occlusion, the dogs were killed, the hearts were excised, and the left ventricle was sectioned parallel to the atrioventricular groove; infarct size was determined planimetrically after incubation in triphenyl tetrazolium chloride. The slices were then exposed to high-speed x-ray film with image-enhancing screens. The percentage of left ventricle that was ischemic, as determined by planimetry of autoradiographs, was similar in treated and control animals (36.6 +/- 2.0% compared to 37.3 +/- 2.8%, respectively). Of the ischemic area, 92.0 +/- 4.3% was infarcted in control animals and 70.5 +/- 5.1% was infarcted in treated animals (P < 0.01). Thus, this autoradiographic method using 99mTc-labeled human albumin microspheres is useful in delineating the area of ischemia after coronary artery occlusion and in evaluating the efficacy of pharmacologic agents designed to protect ischemic myocardium. Verapamil, administered 1 hr after coronary artery occlusion, is effective in limiting infarct size.

BACKGROUND: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a potentially lifesaving maneuver in the setting of hemorrhagic shock. However, emergent use of REBOA is limited by existing technology, which requires large sheath arterial access and fluoroscopy-guided balloon positioning. The objectives of this study were to describe a new, fluoroscopy-free REBOA system and to compare its efficacy to existing technology. An additional objective was to characterize the survivability of 60 minutes of REBOA using these systems in a model of hemorrhagic shock. METHODS: Swine (70-88 kg) in shock underwent 60 minutes of REBOA using either a self-centering, one component prototype balloon system (PBS, n = 8) inserted (8 Fr) and inflated without fluoroscopy or a two-component, commercially available balloon system (CBS, n = 8) inserted (14 Fr) with fluoroscopic guidance. Following REBOA, resuscitation occurred for 48 hours with blood, crystalloid, and vasopressors. End points included accurate balloon positioning, hemodynamics, markers of ischemia, resuscitation requirements, and mortality. RESULTS: Posthemorrhage mean arterial pressure (mm Hg) was similar in the CBS and PBS groups (35 [8] vs. 34 [5]; p = 0.89). Accurate balloon positioning and inflation occurred in 100% of the CBS and 88% of the PBS group. Following REBOA, mean arterial pressure increased comparably in the CBS and PBS groups (81 [20] vs. 89 [16]; p = 0.21). Lactate peaked in the CBS and PBS groups (10.8 [1.4] mmol/L vs. 13.2 [2.1] mmol/L; p = 0.01) 45 minutes following balloon deflation but returned to baseline by 24 hours. Mortality was similar between the CBS and PBS groups (12% vs. 25%, p = 0.50). CONCLUSION: This study reports the feasibility and efficacy of a novel, fluoroscopy-free REBOA system in a model of shock. Despite a significant physiologic insult, 60 minutes of REBOA is tolerated and recoverable. Development of lower profile, fluoroscopy-free endovascular balloon occlusion catheters may allow proactive aortic control in patients at risk for hemorrhagic shock and cardiovascular collapse.

The ultimate goal of implantable electrochemical, aptamer-based (E-AB) sensors is to enable the continuous and precise monitoring of clinically and physiologically important targets in the body for prolonged periods.

Although functional endoscopic sinus surgery is an effective means of treating patients with recurrent and refractory sinusitis, the procedure is not without risk of serious surgical complications. Preoperative computed tomography (CT) affords radiologists the opportunity to prospectively identify anatomic variants that predispose patients to major surgical complications; however, these critical variants are not consistently evaluated or documented on preoperative imaging reports. The purpose of this review is to illustrate important anatomic variants and landmarks on the preoperative sinus CT with a focus on those that predispose patients to surgical complications. These critical variants and landmarks can be quickly recalled and incorporated into the preoperative imaging report through the use of the mnemonic "CLOSE": Cribriform plate, Lamina papyracea, Onodi cell, Sphenoid sinus pneumatization, and (anterior) Ethmoidal artery. This approach will greatly enhance the value of the preoperative imaging report for referring otolaryngologists and help reduce the risk of surgical complications. (©) RSNA, 2016 Online supplemental material is available for this article.