The factors affecting mortality in intensive care unit of a burns center.

OBJECTIVE: To determine the characteristics of patients, mortality-affecting factors and mortality rate in follow-up burn-injured patients in an intensive care setting at a burns treatment centre. Methods: The retrospective study was conducted between May and November 2014 at Kocaeli Derince Training and Research Hospital Burn Treatment Centre, Kocaeli, Turkey, and comprised data from January 2008 to January 2013 of in-patients who had been treated at the intensive care unit. The therapy outcomes and the follow-up processes were evaluated. Data was analysed using SPSS 17. RESULTS: Of the 381 patients, 105(27.6%) were females and 276(72.4%) were males. The overall mean age was 28.4±21.1 years. There were 52(13.6%) mortalities, while 329(86.4%) survived. The mean total body surface area was 18.3±12.9% in those who survived compared to 52±24.3% in those who died (p<0.000). The highest rate of death was observed in those aged >66 years (p<0.000). The impact of flame burns on mortality was statistically significant (p<0.05). The impact of inhalation burns, suicide, abuse, operational requirements and systemic disease on mortality was statistically significant (p<0.05). CONCLUSIONS: Older age, higher total body surface area, flame burns, presence of inhalation burn, third degree burn, suicide attempt, presence of systemic disease, duration of prolonged mechanical ventilation and operation requirements were found to be poor prognostic factors for survival in burn patients.

Mini Anterior Incision versus Conventional Incision in Thyroid Operations.

OBJECTIVE: To analyse the results of mini anterior incision compared to conventional Kocher's incision in total thyroidectomy. STUDY DESIGN: Observational cohort study. PLACE AND DURATION OF STUDY: Department of General Surgery, Breast, and Endocrine Surgery Clinic, Ankara City Hospital, Turkey, from March 2019 to December 2019. METHODOLOGY: Four hundred and twenty-five patients who underwent total thyroidectomy (TT) were divided into two groups; 132 patients in group 1 (mini anterior incision group) and 293 patients in group 2 (conventional incision group). Patient examination and follow-up findings were obtained from the hospital information system software (HIS). A questionnaire to verify the satisfaction of patients on different parameters was also completed by the researcher. RESULTS: Mini anterior incision significantly reduced incision length, scar thickness, discharge time, time to get back to work (p <0.001, p <0.001, p = 0.027, and p = 0.006, respectively). There was also less pain in the neck or surgical area in group 1 and less explicit or inconspicuous scar (p = 0.001 and p <0.001, respectively). Patients in group 1 found their surgery more aesthetic (p = 0.001). Central lymph node dissection (CLND) was performed in 21.31% of the patients with thyroid cancer in group 1. CONCLUSION: More aesthetic results can be obtained by performing wound lip excision using a mini anterior incision. By using a mini anterior incision, CLND can be performed as effectively as with conventional incision in thyroid operations. KEY WORDS: Minimally invasive thyroid surgery, Mini anterior incision, Thyroidectomy, Cosmetic surgery.

External Validation of a Nomogram Developed for Predicting Overall Survival in Gastric Cancer Patients with Insufficient Number of Examined Lymph Nodes.

Objectives: Nomograms and scoring systems in gastric cancers have been mainly developed based on adequate lymph node (lN) dissections. This study aimed to perform external validation of a nomogram developed for predicting overall survival (OS) in gastric cancer patients with insufficient number of examined LNs (eLNs) and to evaluate its usability as compared with the 8th American Joint Committee on Cancer (AJCC)'s Tumor-Node-Metastasis staging system. Methods: Medical records of 262 patients undergoing complete surgical resection for gastric cancers and having pathologically confirmed diagnosis were retrospectively reviewed. The study included 104 (39.7%) patients (82 males, median age, 60.3 years) with insufficient number of eLNs (<16). The 5-year OS rate was calculated using the nomogram and according to the AJCC system. Results: The median follow-up period was 37.4 months (range: 0.9-122.9). Of the patients, 69 (66.3%) died and 35 (33.7%) achieved 5-year survival within the follow-up period. The nomogram and the AJCC system predicted OS were significantly lower in patients who died than in those who achieved 5-year survival (p<0.001 for both). According to the receiver operative characteristics-curve, the area under the curve for the nomogram (0.801; 95% CI, 0.715-0.887; p<0.001) was larger than that for the AJCC system (0.754; 95% CI, 0.659-0.849; p<0.001). Conclusion: The nomogram developed for gastric cancer patients with insufficient number of eLNs (<16) was effective in predicting 5-year OS in our cohort and was superior to the AJCC system.

Does Albumin Level Change the Strength of the Memorial Sloan Kettering Cancer Center Nomogram Used to Predict 5-year Survival in Patients with Colon Cancer?

OBJECTIVE: To test the efficacy of including albumin in the Memorial Sloan Kettering Cancer Center (MKSCC) nomogram (MSKCC+A) on predicting the overall survival. STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: Ankara Training and Research Hospital & Ataturk Training and Research Hospital, Turkey, in 2020, on patients who were operated between 2009 and 2014 to confirm the 5-year survival results. METHODOLOGY: Patients who underwent R0 resection for colon cancer were evaluated. For each patient in the cohort, the 5-year probability of survival was calculated and compared with actual, using the AJCC (American Joint Committee on Cancer), MSKCC and MSKCC+A estimation systems obtained using logistic regression. The performance of the estimation methods was evaluated by the ROC analysis. RESULTS: Two hundred and thirty-nine patients were studied. When the patients with more than 5-year overall survival were compared, the AJCC, MSKCC, and enhanced MSKCC survival scores were significantly higher. AUC = 0.699 for the AJCC staging system, AUC = 0.702 for the MKSCC nomogram, and AUC = 0.777 when the albumin level was added to the MKSCC system. CONCLUSIONS: The use of the MSKCC overall survival nomogram in patients with colon cancer appears useful for both clinicians and patients. The prognostic power of this calculator was found to be further enhanced by including the preoperative serum albumin level as an extra variable in the nomogram. KEY WORDS: Nomograms, Neoplasm grading, Survival, Colon cancer, Serum albumin.

Risks and prediction of postoperative hypoparathyroidism due to thyroid surgery.

We aimed to investigate the prevalence of postoperative hypoparathyroidism (PoH), the relevant factors, and predictors of transient or permanent hypoparathyroidism. The files of 352 patients who underwent bilateral total thyroidectomy alone or with central lymph node dissection and/or lateral neck dissection between June 1, 2019, and November 30, 2019, were retrospectively evaluated. Also, calcium and parathyroid hormone levels measured preoperatively and 4-6 h after surgery, follow-up examination results, and time to resolution of transient PoH were recorded. 16.48% (n = 58) of the surgical patients developed transient PoH and 3.98% (n = 14) developed permanent PoH. Length of hospital stay increased in patients who developed PoH (p < 0.001). Transient PoH developed less in patients who underwent parathyroid autotransplantation, while permanent PoH was not detected (p = 0.001). PoH development was not significantly correlated with nodule size as measured by preoperative thyroid ultrasonography (p = 0.944). Patients who had a serum PTH level ≤ 5.95 pmol/L 4-6 h after surgery had a greater risk of developing permanent PoH (OR 134.84, 95% CI 17.25-1053.82). PoH is more common in female gender and is not significantly correlated with nodule size. Parathyroid autotransplantation can prevent the development of PoH.

The diagnostic role of testicular fatty acid-binding protein in testicular ischemia: A randomized controlled experimental study. / El papel de la proteína testicular acido graso en la isquemia testicular: estudio experimental randomizado.

OBJECTIVE: To investigate the diagnostic value of testicular fatty acid-binding protein (T-FABP) in acute testicular ischemia and prolonged ischemia. METHODS: The study included a total of 28 prepubertal male Wistar-Hannover rats. The animals were randomly divided into 4 groups as torsion groups (group I; min 30; 7 rats, group II; min 120; 7 rats, group III; min 240; 7 rats) and control group (group IV; 7 rats). In each group, the left testis was separated from the gubernaculum by blunt dissection together with the tunica vaginalis and spermatic cord, and then exposed. In the control group, the blood samples and left testicular tissues were collected at min 240 after extraction. In torsion groups, the left testis was rotated together with its cord elements,720° in a clockwise direction for the induction of an extravaginal TT model. The blood samples were obtained at min 30, 120, and 240 in the torsion groups. Bilateral testicular tissues were collected via orchiectomy for histopathological examination in all groups. RESULTS: The mean plasma T-FABP level in group III (torsion, min 240) was significantly higher than those of other groups. The T-FABP level at min 240 had a sensitivity and specificity of 100% and 85%, respectively, at a cut-off value of 1.059. A significant difference was found between the torsion groups and the control group with regard to histopathological scores. CONCLUSIONS: The increased T-FABP levels in testicular ischemia seem to be correlated with testicular necrosis rather than acute ischemia.

OBJETIVO: Investigar el valor diagnostico de la proteína testicular acido graso (PTAG) en la isquemia testicular aguda y prolongada. MÉTODOS: El estudio involucró 28 ratas Wastar-Hannover varones prepuberales. Los animales fueron randomizados y divididos en 4 grupos: grupo torsión (grupo I; min 30; 7 ratas, grupo II; min 120; 7 ratas, grupo III; min 240; 7 ratas), grupo control (grupo IV; 7 ratas). En cada grupo, el testículo izquierdo fue separado del gubernáculo con disección, junto con la túnica vaginalis y el cordón espermático, y después fueron expuestos. En el grupo control, la extracción de sangre y tejido testicular izquierdo fueron recolectados a los 240 minutosde la extracción. En el grupo de torsión, el testículo izquierdo se rotó junto con los elementos del cordón espermático, 720 grados en la dirección de las agujas del reloj para la inducción de un modelo TT extravaginal. Las muestras de sangre fueron obtenidas a los 30 minutos, 120 y 240 minutos en los grupos torsión. Tejido testicular bilateral fue recogido vía orquiectomia para examen anatomopatológico en todos los grupos. RESULTADOS: El nivel medio de PTAG en el grupo III (torsión 240 min) fue significativamente superior a los demás grupos. El nivel de PTAG a los 240 minutos tuvo una sensibilidad y especificidad del 100% y 85%, respectivamente a un valor de corte de 1.059. Se encontró una diferencia significativa entre los grupos de torsión y control en relación a los "scores" anatomopatológicos. CONCLUSIONES: Los niveles elevados de PTAG en la isquemia testicular parecen correlacionados con la necrosis testicular más que con la isquemia aguda.

The diagnostic role of testicular fatty acid-binding protein in testicular ischemia: a randomized controlled experimental study / El papel diagnóstico de la proteína fijadora de ácidos grasos testiculares en la isquemia testicular: un estudio experimental controlado aleatorizado

Objetive: To investigate the diagnosticvalue of testicular fatty acid-binding protein (T-FABP) inacute testicular ischemia and prolonged ischemia.Methods: The study included a total of 28 prepubertal male Wistar-Hannover rats. The animals were randomly divided into 4 groups as torsion groups (group I;min 30; 7 rats, group II; min 120; 7 rats, group III; min240; 7 rats) and control group (group IV; 7 rats). In eachgroup, the left testis was separated from the gubernaculum by blunt dissection together with the tunica vaginalisand spermatic cord, and then exposed. In the controlgroup, the blood samples and left testicular tissues were collected at min 240 after extraction. In torsion groups,the left testis was rotated together with its cord elements,720° in a clockwise direction for the induction of an extravaginal TT model. The blood samples were obtainedat min 30, 120, and 240 in the torsion groups. Bilateraltesticular tissues were collected via orchiectomy for histopathological examination in all groups.Results: The mean plasma T-FABP level in group III (torsion, min 240) was significantly higher than those ofother groups. The T-FABP level at min 240 had a sensitivity and specificity of 100% and 85%, respectively, ata cut-off value of 1.059. A significant difference wasfound between the torsion groups and the control groupwith regard to histopathological scores.Conclusions: The increased T-FABP levels in testicular ischemia seem to be correlated with testicular necrosis rather than acute ischemia.(AU)

Objetivo: Investigar el valor diagnosticode la proteína testicular acido graso (PTAG) en la isquemia testicular aguda y prolongada.Métodos: El estudio involucro 28 ratas Wastar-Hannover varones prepuberales. Los animales fueron randomizados y divididos en 4 grupos: grupo torsión (grupoI; min 30; 7 ratas, grupo II; min 120; 7 ratas, grupoIII; min 240; 7 ratas), grupo control (grupo IV; 7 ratas).En cada grupo, el testículo izquierdo fue separado delgubernáculo con disección, junto con la túnica vaginalisy el cordón espermático, y después fueron expuestos.En el grupo control, la extracción de sangre y tejidotesticular izquierdo fueron recolectados a los 240 minutos de la extracción. En el grupo de torsión, el testículoizquierdo se rotó junto con los elementos del cordónespermático, 720 grados en la dirección de las agujasdel reloj para la inducción de un modelo TT extravaginal. Las muestras de sangre fueron obtenidas a los30 minutos, 120 y 240 minutos en los grupos torsión.Tejido testicular bilateral fue recogido vía orquiectomiapara examen anatomopatológico en todos los grupos.Resultados: El nivel medio de PTAG en el grupo III(torsión 240 min) fue significativamente superior a losdemás grupos. El nivel de PTAG a los 240 minutos tuvouna sensibilidad y especificidad del 100% y 85%, respectivamente a un valor de corte de 1.059. Se encontróuna diferencia significativa entre los grupos de torsión ycontrol en relación a los “scores” anatomopatológicos.Conclusiones: Los niveles elevados de PTAG enla isquemia testicular parecen correlacionados con lanecrosis testicular más que con la isquemia aguda.(AU)

Experimental Variables that Affect Human Hepatocyte AAV Transduction in Liver Chimeric Mice.

Adeno-associated virus (AAV) vector serotypes vary in their ability to transduce hepatocytes from different species. Chimeric mouse models harboring human hepatocytes have shown translational promise for liver-directed gene therapies. However, many variables that influence human hepatocyte transduction and transgene expression in such models remain poorly defined. Here, we aimed to test whether three experimental conditions influence AAV transgene expression in immunodeficient, fumaryl-acetoactetate-hydrolase-deficient (Fah -/-) chimeric mice repopulated with primary human hepatocytes. We examined the effects of the murine liver injury cycle, human donor variability, and vector doses on hepatocyte transduction with various AAV serotypes expressing a green fluorescent protein (GFP). We determined that the timing of AAV vector challenge in the liver injury cycle resulted in up to 7-fold differences in the percentage of GFP expressing human hepatocytes. The GFP+ hepatocyte frequency varied 7-fold between human donors without, however, changing the relative transduction efficiency between serotypes for an individual donor. There was also a clear relationship between AAV vector doses and human hepatocyte transduction and transgene expression. We conclude that several experimental variables substantially affect human hepatocyte transduction in the Fah -/- chimera model, attention to which may improve reproducibility between findings from different laboratories.

The Diagnostic Values of Ischemia-Modified Albumin in Patients with Acute Abdominal Pain and Its Role in Differentiating Acute Abdomen.

AIM: The aim of this study was to evaluate the diagnostic value of serum ischemia-modified albumin (IMA) levels in patients presenting to the emergency department with acute abdominal pain and its use in differentiating acute surgical abdomen. METHODS: This single-center prospective cross-sectional study included 334 adult patients who presented to the emergency department. These consisted of 194 patients (Group 1) with nontraumatic abdominal pain commencing in the preceding week, who were definitely diagnosed and either hospitalized in a specific department or planned for discharge, and a control group of 140 patients (Group 2). RESULTS: The mean IMA value of the patients diagnosed with acute appendicitis was statistically significantly higher than that of the control group. The mean IMA value of the patients diagnosed with acute appendicitis, ovarian pathologies, and gastritis-peptic ulcer was statistically significantly higher than that of the nonspecific abdominal pain group. CONCLUSION: Serum IMA levels can be used as a diagnostic marker in patients with acute appendicitis. Furthermore, serum IMA levels in patients presenting to the emergency department with abdominal pain may be indicative of patients requiring surgery or of complicated cases, particularly in terms of acute appendicitis and ovarian pathologies.

Evaluation of malignancy with thyroid imaging reporting and data system (TI-RADS) in thyroid nodules with persistent nondiagnostic cytology

Background/aim: We aimed to evaluate the utility of thyroid imaging reporting and data system (TI-RADS) in prediction of malignancy in thyroid nodules with persistent nondiagnostic (ND) cytology. Materials and methods: A total of 246 thyroid nodules which were surgically removed and had at least two fine-needle aspirations (FNAs) with ND cytology were included in this study. Ultrasonography features and TI-RADS scores were recorded. Results: Of 246 nodules, 218 (88.6%) had benign and 28 (11.4%) had malignant final histopathology. Frequencies of taller than wide shape, solidity, hypoechogenicity, microcalcifications, and presence of irregular borders were similar between benign and malignant nodules (P > 0.05). The number of nodules categorized as TI-RADS 3, 4a, 4b, and 4c were 12 (4.9%), 53 (21.5%), 104 (42.3%), and 77 (31.3%), respectively. There was not any nodule in TI-RADS 5 category. Malignancy rates of categories 3, 4a, 4b, and 4c were 0%, 13.2%, 9.6%, 14.3%, respectively. No significant differences were detected in TI-RADS categories between benign and malignant nodules (P > 0.05). Conclusion: In this study, we did not demonstrate any suspicious ultrasound (US) finding predictive for malignancy in thyroid nodules with persistent ND cytology and did not determine any difference between malignant and benign nodules regarding TI-RADS scores. Whereas, we found that thyroid nodules in 4a, 4b, and 4c TI-RADS categories had higher malignancy rates than those previously reported in ND cytology. We think that TI-RADS categories in thyroid nodules with persistent ND cytology can be helpful in treatment decision.

Synthetic mesh placement in the presence of abdominal infection: An experimental study of feasibility.

BACKGROUND: There are varying opinions on the feasibility of the placement of synthetic materials in contaminated surgical fields. The aim of this study was to investigate the outcomes of the use of a commercially available composite mesh in the presence of abdominal infection. METHODS: Twenty-four hours after the induction of experimental peritonitis, 20 rats were randomized into 2 groups of 10 subjects. After abdominal cleansing with a second laparotomy, the abdomen was closed with running sutures in the control group and the composite mesh was applied in the experimental group before closure. The rats were followed up for findings of sepsis, mortality, and wound infection. On the 28th day, the rats were sacrificed and evaluated for abdominal infection, abdominal adhesions, and bacterial growth in the mesh and tissue cultures. RESULTS: The mortality rate was 0% and 30% in the control and mesh groups, respectively (p=0.21), and the wound infection rate was 20% and 57.1% (p=0.162). In the mesh group, the adhesions were significantly more intense (p=0.018) and significantly more microorganisms proliferated in the tissue cultures (p=0.003). CONCLUSION: The significant increase in the intensity of adhesions and bacterial proliferation, as well as the higher rate of mortality and wound infection in the mesh group indicated that this composite mesh cannot be used safely in the repair of abdominal defects in the presence of abdominal infection.

Diagnostic accuracy of Thyroid Imaging Reporting and Data System in the prediction of malignancy in nodules with atypia and follicular lesion of undetermined significance cytologies.

OBJECTIVE: Thyroid Imaging Reporting and Data System (TIRADS) is a simple and reliable reporting system for the prediction of malignancy. We aimed to determine the role of TIRADS in the prediction of malignancy in subcategories of Bethesda Category III, atypia of undetermined significance (AUS) and follicular lesion of undetermined significance (FLUS). DESIGN & PATIENTS: A total of 461 nodules with AUS cytology in 450 patients and 179 nodules with FLUS cytology in 168 patients were included. Ultrasonography (US) features and postoperative histopathology results were documented. Every suspicious US feature was scored as 1 and 0 according to the presence or not, respectively. TIRADS category of each nodule was determined. RESULTS: In AUS subcategory, histopathologically malignant nodules had significantly different TIRADS categories compared to benign nodules (P = 0·001), but this was not the case in FLUS subcategory (P = 0·121). In AUS group, malignant nodules had significantly higher prevalance of microcalcification, hypoechogenicity and anteroposterior/transverse ratio than benign ones (P < 0·001, P < 0·001 and P = 0·003, respectively) and TIRADS categories of 4c and 5 were more frequent in malignant nodules (P < 0·05). Microcalcification, hypoechogenicity and TIRADS were found to be associated with malignancy in multivariate logistic regression analysis in this subcategory. TIRADS category ≥4c was associated with malignancy (AUC ± SE: 0·584 ± 0·028). In FLUS subcategory, there was no significant difference between histopathologically malignant and benign nodules with respect to suspicious US features (P > 0·05, all). CONCLUSION: TIRADS seems to be useful in predicting malignancy and planning further management in the AUS subcategory, but not quite so in the FLUS subcategory.

Effects of acetaminophen and mannitol on crush injuries in rats: An experimental study.

BACKGROUND: The present objective was to evaluate effects of acetaminophen and mannitol on renal function and histopathology in crush injuries. METHODS: Thirty-six rats weighing 370-400 g each were used. No surgery was performed on the first (control) group. The gastrocnemius muscle regions of each rat in the remaining 5 groups were compressed for 2 or 24 hours. In the 4th group, 100 mg/kg acetaminophen was intraperitoneally administered. In the 5th group, 1 g/kg mannitol was administered. In the 6th group, 100 mg/kg acetaminophen and 1 g/kg mannitol were administered. RESULTS: No statistically significant differences were observed among the treatment groups in terms of sodium, potassium, alanine aminotransferase (ALT), and average creatinine clearance values. Hydropic degeneration, tubular necrosis, presence of immunoperoxidase and myoglobin, tubulus epithelial cell degeneration, and presence of PAS-dyed material in tubular lumen was more prominently decreased in the acetaminophen group than the mannitol group. Improvement was observed in the group that was administered both drugs, compared to the mannitol-only group, though findings were still worse than those of the group administered acetaminophen only. CONCLUSION: In crush injuries, acetaminophen improves histopathological renal damage better than mannitol. When used in conjunction with mannitol, the toxic effect of acetaminophen on the liver is decreased.

To decide medical therapy according to ECG criteria in patients with supraventricular tachycardia in emergency department: adenosine or diltiazem.

UNLABELLED: The aim of this study is to investigate the effect of ECG criteria which are used for the distinction between AVNRT and AVRT for the choice of treatment in patients with Supraventricular Tachycardia (SVT). The 77 patients with narrow QRS complex SVT which was treated with Adenosine or Diltiazem in the Emergency Department were evaluated retrospectively. All 12-lead ECG during tachycardia were blindly reviewed according to ECG criteria (Pseudo-r` in V1, Pseudo-S-wave in the inferior leads, Visible P-wave, aVL notch) by a cardiologist and an emergency physician. In this study, while 59.6% of the patients returned to normal sinus rhythm (NSR) after the first dose 6 mg, 64.91% of them after the first dose 12 mg and 71.92% of them after the second dose of 12 mg adenosine, 95% of the patients returned to NSR after the 0.25 mg/kg diltiazem. The most visible ECG findings were visible P waves and the least visible ECG findings were Pseudo-S waves in the inferior leads. It was statistically significant between converted by adenosine to NSR and converted by diltiazem to NSR to the presence of visible P-wave and the aVL lead notch in their ECG findings. CONCLUSION: The rate of return to NSR through diltiazem was found higher than that of adenosine in narrow complex SVT patients. Also, diltiazem may be the first medication to be preferred in the presence of retrograt P wave and aVL notch in the ECG of the patients with narrow QRS complex stable SVT.

A comparison of the outcome of CPR according to AHA 2005 ACLS and AHA 2010 ACLS guidelines in cardiac arrest: multicenter study.

The aim of this study was to evaluate whether there is a difference in the return of spontaneous circulation (ROSC) and survival with sequel-free recovery rates between the patients who underwent cardiopulmonary resuscitation (CPR) according to 2005 and 2010 guidelines. This study was conducted in the Bakirköy Dr. Sadi Konuk and Kartal Lütfi Kirdar Training and Research Hospital between dates of October 2010 and 28 February 2011 after approval of Ethics Committee. In the first months of the study, CPR was performed according to AHA 2005 ACLS guidelines (Group-1), while CPR was performed according to AHA 2010 ACLS guidelines after November 2010 (Group-2). Patients were assessed for neurological deficit with Cerebral Performance Categories Scale. Mean age was found as 69.01±13.05 (minimum: 21, maximum: 92) in 86 patients included. Of the 33 patients underwent CPR in the Group 1, ROSC was achieved in 51.5%; and 6.1% of these patients were discharged. Of the 53 patients underwent CPR in the Group 2, ROSC was achieved in 37.7%; and 9.4% of these patients were discharged. Although the number of living patients in Group 2 was higher than Group 1, the difference was not found statistically significant (5 versus 2), (P>0.05). But, neurological outcomes were found better with 2010 compared to 2005 guidelines (3/7 versus 0/2 good cerebral performance). It was found that the 2005 CPR guidelines practices in ED were more successful than the 2010 CPR guidelines practices in ROSC, but less successful in the rate of discharge from hospital and neurological sequel-free discharge rate.

Rare etiological causes of iliofemoral deep venous thrombosis: Reports of 2 cases.

Deep venous thrombosis is frequently seen in lower extremities. However, when seen in the iliac level, mass effect of an underlying pathology must be considered. In this report, we present two cases with upper region deep venous thrombosis, which had underlying pathologies of appendicitis and non-Hodgkin lymphoma.

Modulation of CD8+ T cell responses to AAV vectors with IgG-derived MHC class II epitopes.

Immune responses directed against viral capsid proteins constitute a main safety concern in the use of adeno-associated virus (AAV) as gene transfer vectors in humans. Pharmacological immunosuppression has been proposed as a solution to the problem; however, the approach suffers from several potential limitations. Using MHC class II epitopes initially identified within human IgG, named Tregitopes, we showed that it is possible to modulate CD8+ T cell responses to several viral antigens in vitro. We showed that incubation of peripheral blood mononuclear cells with these epitopes triggers proliferation of CD4+CD25+FoxP3+ T cells that suppress killing of target cells loaded with MHC class I antigens in an antigen-specific fashion, through a mechanism that seems to require cell-to-cell contact. Expression of a construct encoding for the AAV capsid structural protein fused to Tregitopes resulted in reduction of CD8+ T cell reactivity against the AAV capsid following immunization with an adenoviral vector expressing capsid. This was accompanied by an increase in frequency of CD4+CD25+FoxP3+ T cells in spleens and lower levels of inflammatory infiltrates in injected tissues. This proof-of-concept study demonstrates modulation of CD8+ T cell reactivity to an antigen using regulatory T cell epitopes is possible.

Overcoming preexisting humoral immunity to AAV using capsid decoys.

Adeno-associated virus (AAV) vectors delivered through the systemic circulation successfully transduce various target tissues in animal models. However, similar attempts in humans have been hampered by the high prevalence of neutralizing antibodies to AAV, which completely block vector transduction. We show in both mouse and nonhuman primate models that addition of empty capsid to the final vector formulation can, in a dose-dependent manner, adsorb these antibodies, even at high titers, thus overcoming their inhibitory effect. To further enhance the safety of the approach, we mutated the receptor binding site of AAV2 to generate an empty capsid mutant that can adsorb antibodies but cannot enter a target cell. Our work suggests that optimizing the ratio of full/empty capsids in the final formulation of vector, based on a patient's anti-AAV titers, will maximize the efficacy of gene transfer after systemic vector delivery.

Cellular localization and characterization of cytosolic binding partners for Gla domain-containing proteins PRRG4 and PRRG2.

The genes encoding a family of proteins termed proline-rich γ-carboxyglutamic acid (PRRG) proteins were identified and characterized more than a decade ago, but their functions remain unknown. These novel membrane proteins have an extracellular γ-carboxyglutamic acid (Gla) protein domain and cytosolic WW binding motifs. We screened WW domain arrays for cytosolic binding partners for PRRG4 and identified novel protein-protein interactions for the protein. We also uncovered a new WW binding motif in PRRG4 that is essential for these newly found protein-protein interactions. Several of the PRRG-interacting proteins we identified are essential for a variety of physiologic processes. Our findings indicate possible novel and previously unidentified functions for PRRG proteins.

Mutations in ERK2 binding sites affect nuclear entry.

The MAPK ERK2 can enter and exit the nucleus by an energy-independent process that is facilitated by direct interactions with nuclear pore proteins. Several studies also suggest that the localization of ERK2 can be influenced by carrier proteins. Using import reconstitution assays, we examined a group of ERK2 mutants defective in known protein interactions to determine structural properties of ERK2 that contribute to its nuclear entry. ERK2 mutants defective in binding to substrates near the active site or to basic/hydrophobic docking (D) motifs were imported normally. Several ERK2 mutants defective in interactions with FXF motifs displayed slowed rates of nuclear import. The import-impaired mutants also showed reduced binding to a recombinant C-terminal fragment of nucleoporin 153 that is rich in FXF motifs. Despite the deficit revealed in some mutants via reconstitution assays, all but one of the ERK2 mutants accumulated in nuclei of stimulated cells in a manner comparable with the wild type protein; the mutant most defective in import remained in the cytoplasm. These results further support the idea that direct interactions with nucleoporins are involved in ERK2 nuclear entry and that multiple events contribute to the ligand-dependent relocalization of these protein kinases.