Reasons for participation in a child development study: Are cases with developmental diagnoses different from controls?

BACKGROUND: Current knowledge about parental reasons for allowing child participation in research comes mainly from clinical trials. Fewer data exist on parents' motivations to enrol children in observational studies. OBJECTIVES: Describe reasons parents of preschoolers gave for participating in the Study to Explore Early Development (SEED), a US multi-site study of autism spectrum disorder (ASD) and other developmental delays or disorders (DD), and explore reasons given by child diagnostic and behavioural characteristics at enrolment. METHODS: We included families of children, age 2-5 years, participating in SEED (n = 5696) during 2007-2016. We assigned children to groups based on characteristics at enrolment: previously diagnosed ASD; suspected ASD; non-ASD DD; and population controls (POP). During a study interview, we asked parents their reasons for participating. Two coders independently coded responses and resolved discrepancies via consensus. We fit binary mixed-effects models to evaluate associations of each reason with group and demographics, using POP as reference. RESULTS: Participants gave 1-5 reasons for participation (mean = 1.7, SD = 0.7). Altruism (48.3%), ASD research interest (47.4%) and perceived personal benefit (26.9%) were most common. Two novel reasons were knowing someone outside the household with the study conditions (peripheral relationship; 14.1%) and desire to contribute to a specified result (1.4%). Odds of reporting interest in ASD research were higher among diagnosed ASD participants (odds ratio [OR] 2.89, 95% confidence interval [CI] 2.49-3.35). Perceived personal benefit had higher odds among diagnosed (OR 1.92, 95% CI 1.61-2.29) or suspected ASD (OR 3.67, 95% CI 2.99-4.50) and non-ASD DD (OR 1.80, 95% CI 1.50-2.16) participants. Peripheral relationship with ASD/DD had lower odds among all case groups. CONCLUSIONS: We identified meaningful differences between groups in parent-reported reasons for participation. Differences demonstrate an opportunity for future studies to tailor recruitment materials and increase the perceived benefit for specific prospective participants.

Impact of bodyweight-adjusted antimicrobial prophylaxis on surgical-site infection rates.

BACKGROUND: Antimicrobial prophylaxis (AMP) adjustment according to bodyweight to prevent surgical-site infections (SSI) is controversial. The impact of weight-adjusted AMP dosing on SSI rates was investigated here. METHODS: Results from a first study of patients undergoing visceral, vascular or trauma operations, and receiving standard AMP, enabled retrospective evaluation of the impact of bodyweight and BMI on SSI rates, and identification of patients eligible for weight-adjusted AMP. In a subsequent observational prospective study, patients weighing at least 80 kg were assigned to receive double-dose AMP. Risk factors for SSI, including ASA classification, duration and type of surgery, wound class, diabetes, weight in kilograms, BMI, age, and AMP dose, were evaluated in multivariable analysis. RESULTS: In the first study (3508 patients), bodyweight and BMI significantly correlated with higher rates of all SSI subclasses (both P < 0.001). An 80-kg cut-off identified patients receiving single-dose AMP who were at higher risk of SSI. In the prospective study (2161 patients), 546 patients weighing 80 kg or more who received only single-dose AMP had higher rates of all SSI types than a group of 1615 who received double-dose AMP (odds ratio (OR) 4.40, 95 per cent c.i. 3.18 to 6.23; P < 0.001). In multivariable analysis including 5021 patients from both cohorts, bodyweight (OR 1.01, 1.00 to 1.02; P = 0.008), BMI (OR 1.01, 1.00 to 1.02; P = 0.007) and double-dose AMP (OR 0.33, 0.23 to 0.46; P < 0.001) among other variables were independently associated with SSI rates. CONCLUSION: Double-dose AMP decreases SSI rates in patients weighing 80 kg or more.

Surveillance of surgical site infections by surgeons: biased underreporting or useful epidemiological data?

Surgical site infections (SSIs) significantly increase post-operative morbidity and mortality. SSI surveillance is an established monitoring tool and reduces SSI rates. The purpose of this study was to compare prospective in-hospital SSI surveillance (I) by the surgical staff and (II) additionally by an infection control team (ICT). The reference method (III) was defined by data generated by the surgical team, supplemented by the ICT and completed by post-discharge surveillance with a post-operative follow-up of one year representing the sum of all available resources. During 24 months, all consecutive inpatient procedures (N=6283) were prospectively recorded by the surgical staff until patients' discharge (I). SSI rates were compared with the surveillance performed by the ICT (II) and with the reference method (III). The overall SSI rate (reference method) was 4.7% (N=293), of which 187 (63.8%) were detected in-hospital and 106 (36.2%) after discharge. (I) The surgical staff detected 91/187 (48.7%) of in-hospital SSIs [91/293 (31.0%) of the reference], (II) the ICT an additional 96/187 (51.3%) during hospitalisation [96/293 (32.8%) of the reference]. Further cross-checking as performed in the visceral surgery department increased the surgeons' detection rate (I) to 59/105 (56.2%) of in-hospital SSIs [59/147 (40.1%) of the reference]. SSI surveillance by the surgical staff detects almost half of all in-hospital SSIs and has the potential to increase the detection rate by simple interventions such as cross-checking. Such a relatively inexpensive surveillance system is an option for hospitals without an ICT or for low risk surgical procedures. Moreover, trends in SSI rates can easily be detected, allowing early intervention.

[The patient with a stoma]. / Der Patient als Stomaträger.

After formation of a stoma patients quality of life can be compromised. This includes body image, capacity to work, leisure time and sexual activity. After leaving the hospital it is essential, that stoma patients are supported by professionals on the long run. This can be achieved by a network of stoma-care nurses, social workers and psychology professionals.

Encapsulation into sterically stabilised liposomes enhances the immunogenicity of melanoma-associated Melan-A/MART-1 epitopes.

Tumour-associated antigens (TAA)-specific vaccination requires highly immunogenic reagents capable of inducing cytotoxic T cells (CTL). Soluble peptides are currently used in clinical applications despite an acknowledged poor immunogenicity. Encapsulation into liposomes has been suggested to improve the immunogenicity of discrete antigen formulations. We comparatively evaluated the capacity of HLA-A2.1 restricted Melan-A/MART-1 epitopes in soluble form (S) or following inclusion into sterically stabilised liposomes (SSL) to be recognised by specific CTL, to stimulate their proliferation and to induce them in healthy donors' peripheral blood mononuclear cells (PBMC), as well as in melanoma-derived tumour-infiltrating lymphocytes (TIL). HLA-A2.1(+), Melan-A/MART-1-NA-8 melanoma cells served as targets of specific CTL in 51Cr release assays upon pulsing by untreated or human plasma-treated soluble or SSL-encapsulated Melan-A/MART-1 27-35 (M27-35) or 26-35 (M26-35) epitopes. These reagents were also used to stimulate CTL proliferation, measured as 3H-thymidine incorporation, in the presence of immature dendritic cells (iDC), as antigen-presenting cells (APC). Induction of specific CTL upon stimulation with soluble or SSL-encapsulated peptides was attempted in healthy donors' PBMC or melanoma-derived TIL, and monitored by 51Cr release assays and tetramer staining. Na-8 cells pulsing with SSL M27-35 resulted in a five-fold more effective killing by specific CTL as compared with equal amounts of S M27-35. Encapsulation into SSL also provided a partial (50%) protection of M27-35 from plasma hydrolysis. No specific advantages regarding M26-35 were detectable in these assays. However, at low epitope concentrations (

Phase I/II clinical trial of a nonreplicative vaccinia virus expressing multiple HLA-A0201-restricted tumor-associated epitopes and costimulatory molecules in metastatic melanoma patients.

We performed a phase I/II clinical trial in metastatic melanoma patients with an ultraviolet (UV)-inactivated nonreplicating recombinant vaccinia virus enabling the expression, from a single construct, of endoplasmic reticulum-targeted HLA-A0201-restricted Melan-A/MART-1(27-35), gp100(280-288), and tyrosinase(1-9) epitopes, together with CD80 and CD86 costimulatory proteins. Corresponding soluble peptides were used to boost responses and granulocyte-macrophage colony-stimulating factor was used as systemic adjuvant. Safety and immunogenicity, as monitored with in vitro-restimulated peripheral blood mononuclear cells by cytotoxic T lymphocyte precursor (CTLp) frequency analysis and tetramer staining, were specifically addressed. Of 20 patients entering the protocol, 2 had to withdraw because of rapidly progressing disease. Immune responses were evaluated in 18 patients (stage III, n = 5; stage IV, n = 13) and increases in specific CTLp frequencies were observed in 15. In 16 patients responsiveness against all 3 antigens could be analyzed: 7 (43%), including all stage III cases, showed evidence of induction of CTLs specific for the three epitopes, and 2 (12%) and 4 (25%), respectively, showed reactivity against two or one tumor-associated antigen. In three stage IV patients no specific CTL reactivity could be induced. Increases in CTLp frequency were detected mostly after viral vaccine injections. However, in a majority of patients final CTLp levels were comparable to initial levels. Tetramer characterization of Melan-A/MART-1(27-35)-specific CTLs during the protocol also suggested preferential expansion after recombinant virus administration. Vector-specific humoral responses, frequently undetectable in stage IV patients, did not appear to prevent tumor-associated antigen-specific CTL induction. Aside from a single occurrence of transient grade 3 leukopenia, no major clinical toxicity was reported. Seventeen of 18 patients completed the 3-month trial (one patient died before the last delayed-type hypersensitivity test). Three displayed regression of individual metastases, seven had stable disease, and progressive disease was observed in seven patients. This is the first report on the administration of a UV-inactivated recombinant vaccinia virus coexpressing five transgenes in cancer patients. The results described here, in terms of safety and immunogenicity, support the use of this reagent in active specific immunotherapy.

Perioperative detection of disseminated tumour cells is an independent prognostic factor in patients with colorectal cancer.

BACKGROUND: The objective of the present investigation was to assess the prognostic significance of disseminated tumour cells in peritoneal lavage, and peripheral and mesenteric venous blood in patients undergoing curative resection of colorectal cancer. METHODS: The prognostic impact of perioperative cytological and immunocytochemical detection of disseminated colorectal cancer cells was evaluated prospectively. Peritoneal lavage fluid, and peripheral and mesenteric venous blood from 53 consecutive patients undergoing curative surgery for colorectal cancer were analysed. The dichotomous results (positive versus negative) from the cytological and immunocytochemical analysis were used as a predictor along with other co-variates in proportional hazard regression models of disease-free and overall survival. RESULTS: Disseminated colorectal cancer cells were found in 13 of 53 patients (25 per cent) using cytology (CYT) and/or immunocytochemistry (ICC). The median follow-up at the time of the analysis was 37 months. In multivariate proportional hazard regression models CYT/ICC status was a significant predictor for disease-free (P = 0.002) and overall (P = 0.006) survival. CONCLUSION: Disseminated tumour cells detected by CYT and ICC represent an independent prognostic factor in patients undergoing surgery for colorectal cancer and may identify patients at high risk of recurrence.

Peritoneal mesothelioma after environmental asbestos exposure.

Mesothelioma are primary malignant neoplasms of the serous membranes. They usually involve the pleura and rarely the pericardium, the peritoneum and the tunica vaginalis testis. About 90% are associated with exposure to asbestos. The exposure is generally occupational, an environmental inhalation of asbestos and asbestiform fibers in areas in Turkey has been observed and presents a major health problem. This report of a patient from Anatolia with peritoneal mesothelioma after environmental exposure outlines the importance of considering this pathology in the differential diagnosis of a Turkish patient presenting with ascites.

[Malignant transformation of perianal Buschke-Löwenstein tumor. Extensive abdominoperineal rectum excision and reconstruction with transpelvic myocutaneous rectus abdominis muscle flap]. / Maligne entarteter perianaler Buschke-Löwenstein-Tumor. Ausgedehnte abdominoperineale Rektumamputation und Rekonstruktion mit transpelvinem myokutanem M.-rectus-abdominis-Lappen.

INTRODUCTION: The Buschke Löwenstein tumor (giant condyloma) in its perianal variant is an extremely rare disease caused by human papilloma virus. Although of histologically benign appearance, it infiltrates and destroys the surrounding tissue. There is a high risk of local recurrence and malignant transformation. The treatment of choice is wide surgical resection. CASE: A 56-year-old woman presented with perianal giant condyloma infiltrating the rectum and vagina. The extensive soft tissue defect resulting from wide resection was filled with a transpelvic myocutaneous rectus abdominis flap. Histology showed a squamous cell carcinoma arising in the Buschke Löwenstein tumor with clear resection margins. Therefore, the patient was irradiated locally after uneventful primary wound healing. CONCLUSION: A simultaneous reconstruction of a large pelvinoperineal soft tissue defect with the transpelvic myocutaneous rectus abdominis flap allows primary healing, accelerated rehabilitation, and safe adjuvant radiotherapy without risk of serious radiation damage to the small bowel by preventing it from protruding into the pelvic defect.

Immunogenicity of nonreplicating recombinant vaccinia expressing HLA-A201 targeted or complete MART-1/Melan-A antigen.

The effect on immunogenicity of different tumor T cell epitope formulations was evaluated in vitro using nonreplicating recombinant vaccinia vector expressing two forms of the melanoma-associated MART-1/Melan-A antigen. The first recombinant virus expressed a minigene encoding a fusion product between an endoplasmic reticulum (ER)-targeting signal and the HLA-A201 binding 27-35 peptide. The second viral construct encoded the complete MART-1/Melan-A protein. The capacity of HLA-A201 cells infected with either viral construct to generate and to stimulate MART-1/Melan-A 27-35 specific cytotoxic T-lymphocytes (CTL), was comparatively characterized. The results obtained here with a tumor antigen confirmed the capacity of vaccinia virus-encoded ER-minigene to generate a very strong antigenic signal. In cytotoxicity assays, recognition of target cells infected with high amounts of both recombinant viruses with activated specific CTL clones, resulted in similar lytic activity. With regard to calcium mobilization, TCR down-regulation, IFN-gamma release, and T cell proliferation assays, the targeted epitope elicited 10- to 1000-fold stronger responses. Remarkably, the immunogenic difference between the two formulations, in their respective capacity to generate CTL from naive HLA-A2 peripheral blood mononuclear cells in vitro as measured by tetramer detection, was lower (2- to 3-fold). Recombinant vectors expressing complete antigens have demonstrated their capacity to generate specific responses and such vaccines might take advantage of a broader potential of presentation. However, as demonstrated here for the HLA-A201-restricted MART-1/Melan-A immunodominant epitope, nonreplicative vaccinia virus expressing ER-targeted minigenes appear to represent a significantly more immunogenic epitope vaccine formulation.

Advanced breast biopsy instrumentation for the evaluation of impalpable lesions: a reliable diagnostic tool with little therapeutic potential.

OBJECTIVE: To assess the potential of advanced breast biopsy instrumentation (ABBI) to clarify the diagnosis of impalpable mammographic lesions and to remove the entire malignant lesions with clear margins. DESIGN: Prospective assessment in a consecutive series of patients. SETTING: University hospital, Basel, Switzerland. SUBJECTS: 139 patients presenting with 144 impalpable microcalcifications or solid nodular densities evident on screening and follow-up mammograms that were suspicious of malignancy. MAIN OUTCOME MEASURES: Feasibility, sensitivity, efficiency in obtaining definitive diagnoses in an outpatient clinic under local anaesthesia, feasibility of complete removal of a primary malignancy, and intervention-related morbidity. RESULTS: The ABBI procedure was successful in 135/144 (94%); an accurate diagnosis was made in 129/130 patients followed up (99%), sensitivity for malignant lesions was 31/32 (97%) and there were 2 complications (2%). Margins of the biopsy cylinder contained a malignant lesion in 26/31 (84%). CONCLUSIONS: Excisional biopsy using the ABBI system is a reliable diagnostic tool with a low morbidity. As in other published series margins were often not clear of tumour and therefore the therapeutic use of the ABBI procedure is limited.

[The Advanced Breast Biopsy Instrumentation (ABBI) for evaluation of mammographically suspicious, non-palpable findings of the breast: a reliable diagnosis with minor therapeutic potential]. / Die Advanced Breast Biopsy Instrumentation (ABBI) für die Evaluation mammographisch verdächtiger, nicht-palpabler Befunde der Brustdrüse: Eine zuverlässige Diagnostik mit geringem therapeutischen Potential.

BACKGROUND: Stereotactic biopsy techniques supersede conventional hook-wire localization followed by open excision to clarify the dignity of nonpalpable mammographic lesions. The advanced breast biopsy instrumentation (ABBI) allows stereotactically guided excision of a specimen up to 20 mm in diameter on an outpatient basis under local anaesthesia. METHODS: Demographic information, mammographic and pathological findings, complications, subsequent interventions and sensitivity as well as efficiency of a series of 144 planned ABBI procedures were documented (largest published single institution series). RESULTS: The ABBI procedure was successfully performed in 93.8% (135/144); accurate diagnosis was made in 99.3% (134/135), sensitivity for malignant lesions was 96.9% (31/32) and morbidity was 1.5%. Consistent with other published series margins of the biopsy cylinder containing a malignant lesion were involved in 83.9% (26/31). CONCLUSIONS: Excisional biopsy using the ABBI system is a reliable diagnostic tool with a low incidence of morbidity. The therapeutic use is of limited potential.

[Small breast carcinomas--less axillary surgery?]. / Kleine Mammakarzinome--weniger axilläre Chirurgie?

In view of introducing less invasive or selective axillary procedures for small breast cancers we investigated our own pT1 tumor patients. The incidence of pT1 carcinoma, the nodal involvement of pT1a, b and c, the axillary relapse and the overall survival were analyzed. From 1983 till 1997 185 consecutive patients have been treated for breast cancers with a diameter of < or = 20 mm. The survival data after Kaplan-Meier are based on a cohort of 117 patients with a median follow up of at least seven years. There were seven patients with a pT1a carcinoma, 30 with a pT1b and 148 with pT1c carcinoma. On an average 16 axillary lymph nodes were counted by the pathologists. The axillary involvement clearly depends on the size of the primary tumor: no nodal involvement in patients with pT1a carcinoma, 10% in patients with pT1b carcinoma and 30% in patients with pT1c carcinoma. Not one single axillary relapse was detected after this follow up time. The overall ten years survival for patients with pT1a was 100%, 91% for pT1b, but only 74% for pT1c carcinoma. Screening mammography is expected to detect more small breast cancers in pN0 stage. Risks and benefits of axillary dissection have to be carefully evaluated. Axillary involvement of small breast cancers is rare. Only a minority of patients will benefit from routine axillary lymphadenectomy, while the majority runs the risk of complications. The sentinel lymph node (SLN) procedure offers a selective approach to this dilemma.

Enhanced generation of cytotoxic T lymphocytes using recombinant vaccinia virus expressing human tumor-associated antigens and B7 costimulatory molecules.

In this work, we addressed the possibility to enhance the "in vitro" generation of CTLs recognizing tumor-associated antigens (TAAs) by using an inactivated recombinant vaccinia virus encoding B7.1 and B7.2 costimulatory molecules (rVV-B7.1/2). Antigen presenting cells (APCs) infected by rVV-B7.1/2 and pulsed with MART-1/Melan-A27-35 HLA-A2.1-restricted peptide induced significantly higher specific cytotoxic activity than peptide-loaded APCs infected by wild-type VV, both in VV-sensitized and naive donors. When APCs were infected with a rVV encoding both MART-1/Melan-A27-35 and B7-1/2 (rVV-B7.1/2-M), a significantly more effective CTL generation was observed as compared with cultures stimulated by APCs infected with a rVV encoding the TAA epitope only (rVV-M). These enhancing effects were detectable irrespective of a previous VV-specific sensitization. Most importantly, fibroblasts, devoid of antigen-presenting capacity upon peptide pulsing or infection with rVV-M, could be turned into effective APCs after infection by rVV encoding TAA epitopes and costimulatory molecules. In these experiments, by using separate recombinant viral constructs, we observed a predominant role of B7-1 as compared with B7-2 in the induction of TAA-specific CTLs. Taken together, our data indicate that replication-incompetent rVV encoding TAA epitopes and costimulatory molecules are able to induce highly effective generation of tumor-specific CTLs. Therefore, these vectors could represent valuable clinical tools for immunotherapy of melanoma patients.

[Superficial femoral vein as vascular graft in surgical therapy of mycotic aneurysm of the common iliac artery]. / Die Vena femoralis superficialis als Gefässersatz bei der chirurgischen Therapie eines mykotischen Aneurysmas der Arteria iliaca communis.

A 38-year-old polytoxicomanic male patient developed an occlusion of both popliteal arteries associated with an aneurysm of the right common iliac artery. A septic cause was suspected and an antimycotic therapy was instituted, but the diameter of the aneurysm increased to 3 cm during 6 months. Moreover, multiple periarterial abscesses occurred. The aneurysm was resected and the iliacal axis reconstructed in situ, using a superficial femoral vein interposition. Six months after operation, patency was confirmed by duplex sonography. Phlebodynamic examinations showed normal flow functions at the donor site.

[The Advanced Breast Biopsy Instrumentation (ABBI), a system for stereotactic excision of mammographically suspect nonpalpable findings in the breast]. / Die Advanced Breast Biopsy Instrumentation (ABBI), ein System zur stereotaktischen Exzision mammographisch verdächtiger nicht-palpabler Befunde der Brustdrüse.

Advanced Breast Biopsy Instrumentation (ABBI) allows radiologically guided stereotactic excision of non-palpable radiodense lesions with high accuracy. Tissue cylinders of 5, 10, 15 or 20 mm diameter and of variable lengths can be removed very accurately under local anaesthesia and on an outpatient basis. Thirty-six patients with suspicious clusters of microcalcifications (n = 29) and with round lesions (n = 7) of the breast were qualified for ABBI. We were able to perform the excisional biopsy in a total of 34 patients. The breast of one woman was too small to safely fit into the system and in another woman the lesion could not be visualized by the system. In 2/34 cases (6%), the excision was imprecise due to slight dislocation of the breast parenchyma by the advancing cylinder knife. In one case (3%), ABBI missed the target within a dense mastopathic breast. In all cases the excisions were well tolerated. No wound complications occurred and the cosmetic result was excellent. Histology revealed 28 benign (82%) and 6 malignant (18%) lesions. Among the 27 small microcalcifications there were 3 invasive carcinomas, 3 ductal carcinomas in situ (DCIS), 1 lobular hyperplasia, 14 mastopathies, 1 fibroadenoma, 1 duct papilloma and 4 calcifications in scars. Four of the 7 round-shaped lesions were found to be fibroadenomas, 1 lobular hyperplasia, and 2 mastopathies. With the ABBI system, non-palpable breast lesions can be precisely localized and excised.

Efficacy of specific aseptic precautions for preventing propofol-related infections: analysis by a quality-assurance programme using the explicit outcome method.

Specific aseptic precautions have been recommended for preventing infectious complications of propofol because its lipid base can support bacterial growth if contaminated. To study whether the precautions used at our institution prevent propofol-related infections, we retrospectively analysed the data covering 1 January, 1995 until 30 June, 1996 held in our quality-assurance database. The database contains prospectively collected, detailed and standardized information of each patient's risk factors, anaesthetic and surgical data, and postoperative outcome. Surgical patients who had received propofol for anaesthesia did not have a higher incidence of postoperative infection, thus demonstrating the efficacy of our aseptic precautions.