Is glans penis width a risk factor for complications after hypospadias repair?

INTRODUCTION: Recent studies have suggested that a smaller glans penis size may be associated with a higher likelihood of complications after hypospadias repair. Accurate identification of risk factors other than the well-understood variable of meatal location would allow development of better prognostic models and individualized risk stratification. OBJECTIVE: To test the hypothesis that a smaller width of the glans penis predicts adverse outcomes after hypospadias surgery. METHODS: Prospectively recorded clinical data were reviewed from a single-institution registry of primary hypospadias repairs performed between 2011 and 2014. Follow-up records were examined for occurrence of complications. Urethroplasty complications were defined to include meatal stenosis, dehiscence, urethrocutaneous fistula, urethral stricture, and/or urethral diverticulum. The subset of meatal stenosis and dehiscence were regarded as glanular complications. Regression analyses were performed to determine association between glans width and occurrence of complications. Because pre-operative androgen stimulation is known to increase glans penis size, separate subgroup analyses were included of patients with and without pre-operative use of testosterone cream. RESULTS: A total of 159 patients met criteria for inclusion in the study cohort: 140 patients underwent a single-stage repair, while 19 patients had a two-stage repair. The median glans penis width was 15 mm (range 10-22). Eighty-four patients (53%) received testosterone cream pre-operatively and had a significantly wider glans penis than the 75 patients who did not (median 15.5 vs 14 mm; P < 0.001). Median clinical follow-up was 7 months (IQR 1-12), with a minimum time elapsed since surgery of 10 months at the time of chart review. Twenty-four patients (15%) had one or more urethroplasty complications, including 11 (7%) with glanular complications. Overall, there was no statistically significant association between glans width and urethroplasty complications (P = 0.26) or glanular complications (P = 0.90) (Summary Table). Subgroup analyses of patients with and without pre-operative testosterone also revealed no significant associations between glans width and complications. CONCLUSIONS: Glans penis width was not a risk factor for complications after hypospadias repair. This finding differs from the results of other recent studies and encourages further research into the value of measuring penile parameters in patients undergoing hypospadias repair.

A multicenter phase II study incorporating high-dose rituximab and liposomal doxorubicin into the CODOX-M/IVAC regimen for untreated Burkitt's lymphoma.

BACKGROUND: Despite improvement with intensive multi-agent chemotherapy, 2-year progression-free survival (PFS) rates for adults with high-risk Burkitt's lymphoma (BL) remains <55%. PATIENTS AND METHODS: We conducted a phase II trial for newly diagnosed classic BL utilizing liposomal doxorubicin (Adriamycin) in lieu of doxorubicin and incorporating intravenous rituximab (at 500 mg/m(2) twice/cycle) into the CODOX-M/IVAC regimen. Correlative analyses included paired serum and cerebrospinal fluid (CSF) rituximab levels and close examination of cardiac function. RESULTS: Among 25 BL patients, the median age was 44 years (23-70) and 4 patients were HIV positive. There were 20 high-risk and 5 low-risk patients. At baseline, 40% of high-risk patients had bone marrow involvement, 35% had bulky disease and 15% had central nervous system involvement. The overall response rate was 100% (complete remission 92%). At 34-month median follow-up, the 2-year PFS and overall survival (OS) rates for all patients were 80% and 84%, respectively (low-risk: both 100%; high-risk: 76% and 81%, respectively). Furthermore, the 2-year PFS, OS, and disease-specific survival (DSS) rates for high-risk, HIV-negative patients were 84%, 89% and 100%, respectively. Adverse events (AEs) appeared to be consistent with prior CODOX-M/IVAC data, although there were several grade 3 cardiac events noted (all declined ejection fraction without clinical symptoms). The mean serum rituximab levels at 24 h after cycles 1 and 3 for patients without relapse were 258 and 306 µg/ml, respectively, versus 131 and 193 µg/ml, respectively, for patients with early progression (P = 0.002 and 0.002, respectively). The mean CSF rituximab levels for all patients were 0.11 and 0.24 µg/ml, respectively, at cycle 1 (24/72 h), which equated to serum:CSF ratios of 0.05% and 0.20%, respectively. CONCLUSIONS: The integration of rituximab into CODOX-M/IVAC for adult BL was feasible and tolerable, while changes in cardiac function warrant continued examination. This regimen was associated with excellent survival rates for HIV-negative BL. Further investigation of the predictive value of serum rituximab is needed. Clinicaltrials.gov NCT00392990.

The significance of the ultrasound diagnostics in evaluation of the emboligenic pathogenesis of transient ischemic attacks.

The objective of this study was to examine the possibilities of ultrasound diagnostics in the evaluation of emboligenic pathogenesis of transient ischemic attacks (TIAs) and the frequency of specific origins of embolism. A total of 150 adult patients with TIA and 50 control patients, were examined by neurosonologic, echocardiographic and venous ultrasound examination. Emboligenic pathogenesis of TIA was established in 36.6% of patients. Microembolic signals were detected in 22.7% of the whole group, and 61.8% in emboligenic TIA subgroup. Artery-to-artery embolism from ulcerated plaque of the carotid arteries was found in 12.6% of patients, from the aortic arch atheroma in 3.3% and cardioembolism in 12.6% (atrial fibrillation 7.3%, atrial septal aneurysm 2%, mitral valve prolapse 2%, mechanical heart valve 0.7%, left atrium thrombus 0.7%). Paradoxic embolism with the patent foramen ovale was established in 6% of patients, and with the pulmonary right-to-left shunt in 2%. Correlation with controls showed significantly higher frequency of the ulcerated carotid plaque and frequency of microembolic signals in the TIA group (p < 0.05). The patients with potential sources of embolism had a greater risk of developing TIA than those without these sources.

An open-label, multicenter, phase II study of bevacizumab for the treatment of angiosarcoma and epithelioid hemangioendotheliomas.

BACKGROUND: To determine efficacy and safety of bevacizumab, a recombinant humanized antibody against vascular endothelial growth factor (VEGF), in the treatment of metastatic or locally advanced angiosarcoma and epithelioid hemangioendotheliomas. PATIENTS AND METHODS: In this single-arm phase II trial, 32 patients were enrolled and they received bevacizumab 15 mg/kg IV infusion in 21-day cycles. Patients had disease that was deemed not surgically resectable, Eastern Cooperative Oncology Group (ECOG) performance status of ≤1, adequate organ function and had not received any radiation treatment in the last 28 days. RESULTS: Of the 30 patients evaluated for efficacy and toxic effect, four (two angiosarcoma and two epithelioid hemangioendothelioma; 17%) had a partial response. Fifteen patients (11 angiosarcoma and 4 epithelioid hemangioendothelioma; 50%) showed stable disease with a mean time to progression of 26 weeks. Bevacizumab was well tolerated with only one grade 4 adverse event. Expected known toxic effects of the drug were manageable. CONCLUSION: Bevacizumab is an effective and well-tolerated treatment for metastatic or locally advanced angiosarcoma and epithelioid hemangioendotheliomas. Further phase III studies of bevacizumab in combination with other chemotherapeutic agents and/or radiation treatment are warranted.

Immunological stimuli change expression of genes and neutrophil function in fathead minnow Pimephales promelas Rafinesque.

Fathead minnows Pimephales promelas were exposed to lipopolysaccharide (LPS) and polyinosinic-polycytidylic acid [poly(I:C)] to observe immunological responses during simulated bacterial and viral challenge at the level of gene expression and granulocyte function. Complementary DNA libraries were created from LPS- and poly(I:C)-treated fish and c. 5000 expressed sequence tags (ESTs) were sequenced. The ESTs were subjected to BLASTx analysis and 1500 genes were annotated, grouped by function and 20 immune genes were selected for expression studies by real-time PCR. Lipopolysaccharide treatment significantly downregulated expression of interferon regulatory factor 2 binding protein 1 (nine-fold), Chemokine (C-X-C motif) ligand 12a (three-fold) and TNF-related apoptosis-inducing ligand, TRAIL (two-fold). In poly(I:C)-treated fish, a significant upregulation was observed for IFN-inducible and antiviral proteins belonging to the family of Mx proteins (73-fold) and chemokine CCL-C5a (28-fold). Blood neutrophil count was significantly increased in poly(I:C)-treated fish at 24 and 48 h post-injection. Neutrophil extracellular trap release and respiratory burst of kidney granulocytes were suppressed in poly(I:C)-treated fish, while degranulation of primary granules was not affected significantly by the treatment. The changes in gene expression and neutrophil function in P. promelas exposed to LPS and poly(I:C) support the use of this species as an alternative model for studies of pathogen effects on the innate immune system of fishes.

Rituximab-associated hepatitis B virus (HBV) reactivation in lymphoproliferative diseases: meta-analysis and examination of FDA safety reports.

BACKGROUND: Rituximab has been associated with hepatitis B virus reactivation (HBV-R). However, the characteristics and scope of this association remain largely undefined. METHODS: We completed a comprehensive literature search of all published rituximab-associated HBV-R cases and from the Food and Drug Administration (FDA) Adverse Event Reporting System (AERS) MedWatch database. Literature and FDA cases were compared for completeness, and a meta-analysis was completed. RESULTS: One hundred and eighty-three unique cases of rituximab-associated HBV-R were identified from the literature (n = 27 case reports, n = 156 case series). The time from last rituximab to reactivation was 3 months (range 0-12), although 29% occurred >6 months after last rituximab. Within FDA data (n = 118 cases), there was a strong signal for rituximab-associated HBV-R [proportional reporting ratio = 28.5, 95% confidence interval (CI) 23.9-34.1; Empiric Bayes Geometric Mean = 26.4, 95% CI 21.4-31.1]. However, the completeness of data in FDA reports was significantly inferior compared with literature cases (P < 0.0001). Among HBV core antibody (HBcAb(+)) series, the pooled effect of rituximab-based therapy showed a significantly increased risk of HBV-R compared with nonrituximab-treated patients (odds ratio 5.73, 95% CI 2.01-16.33; Z = 3.33, P = 0.0009) without heterogeneity (χ(2) = 2.12, P = 0.5473). CONCLUSIONS: The FDA AERS provided strong HBV-R safety signals; however, literature-based cases provided a significantly more complete description. Furthermore, meta-analysis of HBcAb(+) series identified a more than fivefold increased rate of rituximab-associated HBV-R.

[Anesthesiologic care of children with neurologic trauma].

Neurotrauma is a leading cause of childhood mortality. Physicians are in a continuous search for means to decrease mortality and morbidity caused by head injury. Treatment of these patients requires familiarity with both cerebral pathophysiology and actions of anaesthetic agents on brain. Early treatment of hypotension and hypoventilation would cut mortality rate by at least one third. Prevention of increased intracranial pressure is the best treatment for head injury. Anaesthetist, neurosurgeon and radiologist should all be members of a team which can secure timely diagnosis and treatment of an injured child. Paying attention to every detail is of huge significance. Treatment of the child in a pediatric trauma center or an accident and emergencies center for adults with both personnel and equipment capable for handling paediatric patients offers greater probability of survival.

Probability of bystander effect induced by alpha-particles emitted by radon progeny using the analytical model of tracheobronchial tree.

Radiation-induced biological bystander effects have become a phenomenon associated with the interaction of radiation with cells. There is a need to include the influence of biological effects in the dosimetry of the human lung. With this aim, the purpose of this work is to calculate the probability of bystander effect induced by alpha-particle radiation on sensitive cells of the human lung. Probability was calculated by applying the analytical model cylinder bifurcation, which was created to simulate the geometry of the human lung with the geometric distribution of cell nuclei in the airway wall of the tracheobronchial tree. This analytical model of the human tracheobronchial tree represents the extension of the ICRP 66 model, and follows it as much as possible. Reported probabilities are calculated for various targets and alpha-particle energies. Probability of bystander effect has been calculated for alpha particles with 6 and 7.69 MeV energies, which are emitted in the (222)Rn chain. The application of these results may enhance current dose risk estimation approaches in the sense of the inclusion of the influence of the biological effects.

Abdominal rectus muscle endometriosis after Cesarean section. Extrapelvic localization of endometriosis.

INTRODUCTION: Endometriosis is defined by the presence of functional endometrial tissue outside the uterus, where it is normally located. Endometriosis could has intra and extra pelvic localization. Abdominal endometriosis is the most common localization of extrapelvic endometriosis and is usually developed in the connective tissue surrounding the operation. Very rarely this could be found in the muscle tissue. The mechanical transplantation theory is responsible for the development of scar endometriosis. CASE REPORT: The patient, 35 years old, three years after caesarian section had an operation because of the assumption for the presence of front abdominal hernia, located at the place of previous section. The egg-sized tumor was removed from the abdominal rectus muscle and sent for PH and immunohistochemical analyses. The results showed endometriosis of the muscle with positive estrogen and progesterone receptors. One year after the operation, due to the repeated pains in the scar area, the treatment continued by GNRH analogues and control was performed by serial ultrasound and biochemical markers CA 125. CONCLUSION: Clinical diagnoses of scar endometriosis could be provided by an accurate anamnesis and physical, ultrasound and biochemical examinations. Scar endometriosis should always be considered when the symptoms are present in cyclic manner, hormone depending, mostly after gynecological operations and worsening during menstruation. The problem was diagnosed by pathohistological analyses (Fig. 4, Ref. 20).

[Results of epidemiological surveillance of hospital infections at the Clinic of Digestive System Surgery, CCS, in 2007].

INTRODUCTION: Nosocomial infections (NI) are significant medical problem in the countries worldwide. NI significance reflects in higher morbidity and mortality rates, and moreover, NIs add to longer stay and higher treatment costs. Based on data obtained from underdeveloped and developing countries, over 20% of hospitalized patients acquire some of NIs, while that proportion is 5% in developed countries. OBJECTIVE: A) to establish the frequency of noosocomial infections at the Clinic of Digestive System Diseases, b) determine the NI incidence in accord with anatomic localizations, c) evaluate the percentage prevalence of NI causes according to anatomic localizations, and d) review the problem of resistance of NI causative agents. MATERIAL AND METHODS: The study of NI incidence was calculated by Center for Diseases and Prevention (CDC) methodology. Sampling, cultivation, isolation, identification and sensitivity tests of cauosative agents to antimicrobial drugs, obtained from patient's material, were carried out by standard microbiological methods in Microbiological laboratory of the Emergency Center, Clinical Center of Serbia. All infections in patients hospitalized at the Clinic of Digestive System Surgery in 2007 were recorded. Data available from medical documentation as well as data obtained from interviews of medical personnel were analyzed. RESULTS: The incidence rates of patients with NI ranged from 1.7-3.4 per 1000 hospital days. Out of a total number of recorded nosocomial infections, surgical site infections accounted for 69%, blood infections 23% and urinary tract infections 6.8%. The most frequent causative agents of surgical site infections in the last year were as follows: Pseudomonas spp (19%), followed by Staphylococcus aureus and Klebsiella spp--(18%), Acinetobacter spp (13%), and Enterococcus spp (8%). Forty percent (40%) of all blood infections verified by laboratory tests in 2007 was caused by coagulase negative Staphylococcus spp (CNS), followed by Acinetobacter spp (18%). Enterococcus spp (11%), and Staphylococcus aureus (7%). The most frequent causative agents of urinary infections were: Escherichia coli (35%) and Enterococcus spp (29%). Over 80% of Staphylococcus aureus isolates were resistant to Methicillin (MRSA) and enterobacteria produced by beta lactamase were recorded (ESBL). CONCLUSION: Enforcement of epidemiological surveillance of nosocomial infections contributes to insight of severity of NI problem, recognition of resistance of causative agents to antibiotics and recommendation of specific preventive measures related to these infections.

[Fibro-osseous pseudotumor of the thumb. Report of a case]. / Pseudotumeur ostéofibreuse du pouce. A propos d'un cas.

Fibro-osseous tumor of the digits is an uncommon, benign condition with an excellent prognosis after local excision. Like myositis ossificans, clinical and histological features may mimic a malignant tumour, especially an extraskeletal osteosarcoma. A correct interpretation of clinical, radiological and histological data is a prerequisite to avoid misdiagnosis and unnecessary radical surgery (for example, amputation). We report the case of a 15-year-old boy who presented with a slow-growing mass of the left thumb, which turned out to be a fibro-osseous tumor on microscopic examination. A complete excision was performed without loss of function. Fifteen months postoperatively, there was no local recurrence.

[Management of cadaveric organ donors].

Because the supply of cadaveric organ donors is limited and their ICU management is complex, a multidisciplinary, well-coordinated, and institutionally supported approach to management is essential to ensure the maintenance of the current supply and to increase the future supply of organs and tissues that are suitable for transplantation. The potential organ donor is at high risk for instability as a direct consequence of the loss of physiologic homeostatic mechanisms that are dependent on functioning of the central nervous system. The keys to successful ICU management of the potential organ donor include a team approach that is focused on the anticipation of complications, appropriate physiologic monitoring, aggressive life support, with frequent reassessment and titration of therapy.

[Hemorrhagic shock].

Hemorrhagic shock is a condition produced by rapid and significant loss of blood which lead to hemodynamic instability, decreases in oxygen delivery, decreased tissue perfusion, cellular hypoxia, organ damage and can be rapidly fatal. Despite improved understanding of the pathophysiology and significant advances in technology, it remains a serious problem associated with high morbidity and mortality. Early treatment is essential but is hampered by the fact that signs and symptoms of shock appear only after the state of shock is well establish and the compensatory mechanisms have started to fail. The primary goal is to stop the bleeding and restore the intravascular volume. This review addresses the pathophysiology and treatment of haemorrhagic shock.

[Coagulopaty in associated with massive transfusion].

Massive hemorrhage is a formidable challenge for anesthesia care providers in the elective setting and poses even greater potential challenges in the trauma setting. In all this cases, the anesthesia care providers are faced with large-volume resuscitations that typically start with crystalloid and colloid and rapidly progress to blood and blood products. These large-volume replacement may cause coagulopathy, which can be difficult to manage in the setting of ongoing blood loss. Coagulopathy associated with massive transfusion is multifactorial event that results from hemodilution, hypothermia, the use of fractionated blood products and disseminated intravascular coagulation. Maintaining a normal body temperature is a first-line, effective strategy to improve hemostasis during massive transfusion. Treatment strategies include the maintenance of adequate tissue perfusion, the corection of anemia, and the use of hemostatic blood products.

Autologous non-myeloablative hematopoietic stem cell transplantation in patients with systemic sclerosis.

Autologous hematopoietic stem cell transplantation (HSCT) utilizing a myeloablative regimen containing total body irradiation has been performed in patients with systemic sclerosis (SSc), but with substantial toxicity. We, therefore, conducted a phase I non-myeloablative autologous HSCT study in 10 patients with SSc and poor prognostic features. PBSC were mobilized with CY and G-CSF. The PBSC graft was cryopreserved without manipulation and re-infused after the patient was treated with a non-myeloablative conditioning regimen of 200 mg/kg CY and 7.5 mg/kg rabbit antithymocyte globulin. There was a statistically significant improvement of modified Rodnan skin score whereas cardiac (ejection fraction, pulmonary arterial pressure), pulmonary function (DLCO) and renal function (creatinine) remained stable without significant change. One patient with advanced disease died 2 years after the transplant from progressive disease. After median follow-up of 25.5 months, the overall and progression-free survival rates are 90 and 70% respectively. Autologous HSCT utilizing a non-myeloablative conditioning regimen appears to result in improved skin flexibility similar to a myeloablative TBI containing regimen, but without the toxicity and risks associated with TBI.

Mobilization, harvesting and selection of peripheral blood stem cells in patients with autoimmune diseases undergoing autologous hematopoietic stem cell transplantation.

Peripheral blood stem cells (PBSC) were mobilized in 130 patients with autoimmune diseases undergoing autologous hematopoietic stem cell transplantation using cyclophosphamide 2 g/m(2) and either granulocyte colony-stimulating factor (G-CSF) 5 mcg/kg/day (for systemic lupus erythematosus (SLE) and secondary progressive multiple sclerosis, SPMS) or G-CSF 10 mcg/kg/day (for relapsing remitting multiple sclerosis (RRMS), Crohn's disease (CD), systemic sclerosis (SSc), and other immune-mediated disorders). Mobilization-related mortality was 0.8% (one of 130) secondary to infection. Circulating peripheral blood (PB) CD34(+) cells/microl differed significantly by disease. Collected CD34(+) cells/kg/apheresis and overall collection efficiency was significantly better using Spectra apheresis device compared to the Fenwall CS3000 instrument. Patients with SLE and RRMS achieved the lowest and the highest CD34(+) cell yields, respectively. Ex vivo CD34(+) cell selection employing Isolex 300iv2.5 apparatus was significantly more efficient compared to CEPRATE CS device. Circulating PB CD34(+) cells/microl correlated positively with initial CD34(+) cells/kg/apheresis and enriched product CD34(+) cells/kg. Mean WBC and platelet engraftment (ANC>0.5 x 10(9)/l and platelet count >20 x 10(9)/l) occurred on days 9 and 11, respectively. Infused CD34(+) cell/kg dose showed significant direct correlation with faster white blood cell (WBC) and platelet engraftment. When adjusted for CD34(+) cell/kg dose, patients treated with a myeloablative regimen had significantly slower WBC and platelet recovery compared to non-myeloablative regimens.

Characterization of a method for profiling gene expression in cells recovered from intact human prostate tissue using RNA linear amplification.

Coupling array technology to laser capture microdissection (LCM) has the potential to yield gene expression profiles of specific cell populations within tissue. However, remaining problems with linear amplification preclude accurate expression profiling when using the low nanogram amounts of RNA recovered after LCM of human tissue. We describe a novel robust method to reliably amplify RNA after LCM, allowing direct probing of 12K gene arrays. The fidelity of amplification was demonstrated by comparing the ability of amplified RNA (aRNA) versus that of native RNA to identify differentially expressed genes between two different cell lines, demonstrating a 99.3% concordance between observations. Array findings were validated by quantitative polymerase chain reaction analysis of a randomly selected subset of 32 genes. Using LCM to recover normal (N=5 subjects) or cancer (N=3) cell populations from intact human prostate tissue, three differentially expressed genes were identified. Independent investigators have previously identified differential expression of two of these three genes, hepsin and beta-microseminoprotein, in prostate cancer. Taken together, the current study demonstrates that accurate gene expression profiling can readily be performed on specific cell populations present within complex tissue. It also demonstrates that this approach efficiently identifies biologically relevant genes.