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Current regimens for the detection and surveillance of bladder cancer are invasive and have suboptimal sensitivity. Here, we present a novel high-throughput sequencing (HTS) method for detection of urine tumor DNA (utDNA) called utDNA CAPP-Seq (uCAPP-Seq) and apply it to 67 healthy adults and 118 patients with early-stage bladder cancer who had urine collected either prior to treatment or during surveillance. Using this targeted sequencing approach, we detected a median of 6 mutations per patient with bladder cancer and observed surprisingly frequent mutations of the PLEKHS1 promoter (46%), suggesting these mutations represent a useful biomarker for detection of bladder cancer. We detected utDNA pretreatment in 93% of cases using a tumor mutation–informed approach and in 84% when blinded to tumor mutation status, with 96% to 100% specificity. In the surveillance setting, we detected utDNA in 91% of patients who ultimately recurred, with utDNA detection preceding clinical progression in 92% of cases. uCAPP-Seq outperformed a commonly used ancillary test (UroVysion, P = 0.02) and cytology and cystoscopy combined (P ≤ 0.006), detecting 100% of bladder cancer cases detected by cytology and 82% that cytology missed. Our results indicate that uCAPP-Seq is a promising approach for early detection and surveillance of bladder cancer. Significance: This study shows that utDNA can be detected using HTS with high sensitivity and specificity in patients with early-stage bladder cancer and during post-treatment surveillance, significantly outperforming standard diagnostic modalities and facilitating noninvasive detection, genotyping, and monitoring. This article is highlighted in the In This Issue feature, p. 453

To characterize the phenotype of pediatric Bickerstaff’s brainstem encephalitis (BBE) and evaluate prognostic features in the clinical course, diagnostic studies, and treatment exposures. We systematically reviewed PubMed, Web of Science, and SCOPUS databases as well as medical records at the Lucile Packard Children’s Hospital to identify cases of pediatric BBE. Inclusion required all of the following criteria: age ≤ 20 years, presence of somnolence or alterations in mental status at the time of presentation or developed within 7 days of presentation, ataxia, and ophthalmoplegia. We reviewed 682 manuscripts, identifying a total of 47 pediatric BBE cases. We also describe five previously unreported cases. The phenotype of these pediatric patients was similar to previously published literature. Sixty-eight percent of patients demonstrated positive anti-GQ1b antibody titers, yet the presence of these antibodies was not associated with longer times to recovery. Patients with neuroimaging abnormalities featured a longer median time to recovery, but this was not statistically significant (p = 0.124). Overall, patients treated with any form of immunotherapy (intravenous immunoglobulin, steroids, or plasmapheresis) demonstrated shorter median time to resolution of symptoms compared to supportive therapy, although this trend was not statistically significant (p = 0.277). Post-hoc t tests revealed a trend towards use of immunotherapy against supportive care alone (p = 0.174). Our study identified clinical, radiologic, and treatment features that may hold prognostic value for children with BBE. The role of immunotherapy remains under investigation but may prove of utility with further, randomized controlled studies in this rare disease.

This study sought to investigate subclinical changes in blood pressure in patients with Down syndrome prior to the acute presentation of patients with moyamoya syndrome (MMS) and compares this to patients with only Down syndrome (DS). 31 patients with MMS treated at Stanford University Hospital were retrospectively reviewed. Three blood pressure recordings from periods 6-12 months, 12-18 months, and 18-24 months, were obtained for each patient. These recordings were then compared against a retrospectively identified cohort of children with only DS. Statistical analysis was performed using generalized linear models with generalized estimating equations to account for blood pressures obtained at multiple time points. Median blood pressure percentiles in patients with MMS and DS from further to closer time-points were noted to be 33.5% (15-52) at 18-24 months, 42% (28-61) at 12-18 months, and 69.5% (39-73) at 6-12 months, compared to 29.3% (21-48.3) average in the DS only controls. There was no significant difference between the 18-24 month and 12-18 month periods (p=0.094), although there was a significant difference between the 6-12 month period and both the 12-18 month period and 18-24 month period (p

Background The first reliable statistic data about perioperatory mortality were published in 1841 by the French Joseph-Francois Malgaigne (1806–1863): he referred to a mean mortality of 60% for amputations and this bad result was to be attributed mainly to hospital acquired diseases. The idea of “hospital acquired disease” although vague, included five infective nosologic entities, which at that time were diagnosed more frequently: erysipelas, tetan, pyemia, septicemia, and gangrene. Nonetheless, the suppuration with pus production was considered from most of the surgeons and doctors of that time as a necessary and unavoidable step in the process of wound healing. During the end of the eighteenth century, hospitals of the main European cities were transforming into aggregations of several wards, where the high concentration of patients created poor sanitary conditions and a consistent increase of perioperatory mortality. In 1865, Lister applied his first antiseptic dressing on the surface of an exposed fracture. These experimental attempts lead to an effective reduction of wound infections respect to the dressing with strings used previously. Discussion Lister's innovations in the field of wound treatment were based on two brand new concepts: germs causing rot were ubiquitarious and the wound infection was not a normal step in the process of wound healing. The concept of antisepsis was hardly accepted in the European surgical world: “Of all countries, Italy is the most indifferent and uninterested in experimenting this method, which has been so favorably judged from the greatest surgical societies in Germany”. This quotation from the young surgeon Giuseppe Ruggi (1844–1925) from Bologna comes from his article where he presented his first experiences on aseptic medications started the previous year in the Surgical Department of Maggiore Hospital in Bologna. In his report, Ruggi described the adopted technique and suggested that the medication should be extended to all the surgical patients of the hospital:“… this is needed to totally remove from the hospital all those elements of infection which grow in the wounds dressed with the old method”. The experimentation of this new dressing for the few treated cases was rigorous and concerned both the sterilization of surgical tools with the fenic acid (5%) and the shaving of the skin. Ruggi also observed that there was no correlation between the seriousness of the wound and its extension or way of healing: when “simple” cases that “should heal without complication” showed fever he often realized that “it was often due to a medication performed without following the rules for an accurate disinfection and dressing”. Ruggi thought that the fever was connected to “reabsorption of pyrogenic substances, which can be removed cleaning and disinfecting the wound” in cases of wounds not accurately dressed and rarely medicated. Frequent postoperative medications of the wound were able to eliminate the fever within 2 h. Ruggi's attitude toward the fine reasoning lead him to introduce the concept of immunodeficiency related to physical deterioration: “… patients treated for surgical disease may sometimes suffer from complications of medical conditions, which initially escape the most accurate investigations… The surgical operation could, in some cases, hold the balance of power”. Conclusions The obtained results, published in 1879, appear extremely interesting. As he wrote in 1898, for the presentation of his case record of more than 1000 laparotomies, he had started “… operating as a young surgeon without any tutor, helped only by his mind and what he could deduce from publications existing at the moment …”.

The CIAO Study (“Complicated Intra-Abdominal infection Observational” Study) is a multicenter investigation performed in 68 medical institutions throughout Europe over the course of a 6-month observational period (January-June 2012). Patients with either community-acquired or healthcare-associated complicated intra-abdominal infections (IAIs) were included in the study. 2,152 patients with a mean age of 53.8 years (range: 4–98 years) were enrolled in the study. 46.3% of the patients were women and 53.7% were men. Intraperitoneal specimens were collected from 62.2% of the enrolled patients, and from these samples, a variety of microorganisms were collectively identified. The overall mortality rate was 7.5% (163/2.152). According to multivariate analysis of the compiled data, several criteria were found to be independent variables predictive of patient mortality, including patient age, the presence of an intestinal non-appendicular source of infection (colonic non-diverticular perforation, complicated diverticulitis, small bowel perforation), a delayed initial intervention (a delay exceeding 24 hours), sepsis and septic shock in the immediate post-operative period, and ICU admission. Given the sweeping geographical distribution of the participating medical centers, the CIAO Study gives an accurate description of the epidemiological, clinical, microbiological, and treatment profiles of complicated intra-abdominal infections (IAIs) throughout Europe.

Background: Primary gastrointestinal stromal tumors (GISTs) are stromal tumors that arise from the gastrointestinal tract. Both surgical resection and molecular therapy are crucial in the treatment of these tumors. This study analyzes the outcomes of 151 patients with GIST treated at 3 institutions. These institutions comprise the GISTologist Study Group and provided follow-up data. Patients and Methods: 151 patients with primary GIST were admitted and treated at the St. Orsola-Malpighi University Hospital in Bologna, Italy, the Catholic University Hospital in Rome, Italy, and the Modena University Hospital and National Cancer Institute in Naples, Italy, over the past 11 years. Patient data as well as tumor and therapy variables were studied to identify factors predicting survival with a focus on the microscopic margins of resection. Results: All 151 patients had primary disease without metastasis and underwent complete resection of gross disease. The 5-year disease-free survival rate was 77%. Disease-free survival was predicted by tumor size, mitotic count, and margins of resection. Recurrence of disease after resection was predominantly intra-abdominal. Conclusions: Tumor size, mitotic count, and microscopic margins of resection predict disease-free survival in patients with primary GIST.

BACKGROUND The incidence of abdominal tuberculosis (TB) is increasing in western and developed countries. This pathology has several complications, including free intestinal perforation. The aim of this study was to analytically summarize all the pertinent literature discussing the various treatments for TB-related perforations. METHODS We reviewed the patient database of the Emergency Surgery Department of the Bologna University Hospital, checking the last 13 years. A retrospective review was conducted of all reported cases of intestinal perforation due to intestinal TB published through 3 March 2009. RESULTS 119 cases of abdominal TB presenting with intestinal perforation were published. There are no standardized guidelines regarding the surgical treatment. Of the 119 reported cases, 40 (33.6%) were treated with resection and anastomosis, 17 (14.2%) with direct sutures, 4 (3.3%) with a simple drain, and in 57, the treatment was not reported. CONCLUSION No clinical evidence has been available for analysis to discern the optimal surgical strategy for treating intestinal perforations induced by TB. The direct closure of the perforation typically correlates with poor morbidity and mortality results. The better treatment seems to be the surgical resection of the perforated part with anastomosis. However, pharmacological therapy remains the essential pillar of treatment.

The use of meshes to repair incisional hernias has been shown to reduce the recurrence rate, though it may increase the risk of surgical site infection. This is one of the most feared and devastating complications of surgical abdominal wall repair. The aim of this work is to describe a new surgical technique that was used to treat two patients suffering from chronic prosthesis infection. Additionally, the outcome of this procedure will be analyzed in terms of its safety, subsequent site infection and recurrence prevention. Two case reports are presented. The procedure was based on a wide surgical excision of the infected prosthesis and the surrounding tissues, plus abdominal wall repair with biological prosthesis. Both patients experienced an uneventful postoperative course. Infection of the surgical site resolved following the procedure and, after a mean follow-up of 36 months, no recurrences of the incisional hernia had occurred. This unique surgical technique not only proved to be safe, but it also solved the chronic prosthesis infection through its use of radical excision, without any postoperative complications or recurrence. This technique confirmed that biological pros theses can be used safely and effectively for implantation in sites of infection.

Contains fulltext : 110654.pdf (Publisher’s version ) (Open Access) ABSTRACT: The CIAO Study is a multicenter observational study currently underway in 66 European medical institutions over the course of a six-month study period (January-June 2012).This preliminary report overviews the findings of the first half of the study, which includes all data from the first three months of the six-month study period.Patients with either community-acquired or healthcare-associated complicated intra-abdominal infections (IAIs) were included in the study.912 patients with a mean age of 54.4 years (range 4-98) were enrolled in the study during the first three-month period. 47.7% of the patients were women and 52.3% were men. Among these patients, 83.3% were affected by community-acquired IAIs while the remaining 16.7% presented with healthcare-associated infections. Intraperitoneal specimens were collected from 64.2% of the enrolled patients, and from these samples, 825 microorganisms were collectively identified.The overall mortality rate was 6.4% (58/912). According to univariate statistical analysis of the data, critical clinical condition of the patient upon hospital admission (defined by severe sepsis and septic shock) as well as healthcare-associated infections, non-appendicular origin, generalized peritonitis, and serious comorbidities such as malignancy and severe cardiovascular disease were all significant risk factors for patient mortality.White Blood Cell counts (WBCs) greater than 12,000 or less than 4,000 and core body temperatures exceeding 38 degrees C or less than 36 degrees C by the third post-operative day were statistically significant indicators of patient mortality.

The CIAO Study is a multicenter observational study currently underway in 66 European medical institutions over the course of a six-month study period (January-June 2012).This preliminary report overviews the findings of the first half of the study, which includes all data from the first three months of the six-month study period.Patients with either community-acquired or healthcare-associated complicated intra-abdominal infections (IAIs) were included in the study.912 patients with a mean age of 54.4 years (range 4-98) were enrolled in the study during the first three-month period. 47.7% of the patients were women and 52.3% were men. Among these patients, 83.3% were affected by community-acquired IAIs while the remaining 16.7% presented with healthcare-associated infections. Intraperitoneal specimens were collected from 64.2% of the enrolled patients, and from these samples, 825 microorganisms were collectively identified.The overall mortality rate was 6.4% (58/912). According to univariate statistical analysis of the data, critical clinical condition of the patient upon hospital admission (defined by severe sepsis and septic shock) as well as healthcare-associated infections, non-appendicular origin, generalized peritonitis, and serious comorbidities such as malignancy and severe cardiovascular disease were all significant risk factors for patient mortality.White Blood Cell counts (WBCs) greater than 12,000 or less than 4,000 and core body temperatures exceeding 38°C or less than 36°C by the third post-operative day were statistically significant indicators of patient mortality.

Background Emergency surgery has become a neglected specialization in Europe and in many other parts of the world. In certain medical fields, emergency surgery isn't even considered an autonomous specialization. However every emergency surgeon must have a good formation in General Surgery but exist huge disparities between different European surgical formative systems. Methods An analysis of the main problems of the European surgical formative system was conducted. Results This discrepancy between formative systems is absolutely unacceptable and presents a notable hazard for the European Union, considering that surgical certifications are reciprocally recognized between programs within all European Union states. Conclusion Considering the increasing possibilities to move inside the European Union, is necessary to improve the European surgical formative system to warrant an uniform formation for all surgeons.

Peritoneal adhesions describe a condition in which pathological bonds form between the omentum, the small and large bowels, the abdominal wall, and other intra-abdominal organs. Different classification systems have been proposed, but they do not resolve the underlying problem of ambiguity in the quantification and definition of adhesions. We therefore propose a standardized classification system of adhesions to universalize their definition based on the macroscopic appearance of adhesions and their diffusion to different regions of the abdomen. By scoring with these criteria, the peritoneal adhesion index (PAI) can range from 0 to 30, unambiguously specifying precise adhesion scenarios. The standardized classification and quantification of adhesions would enable different studies to more meaningfully integrate their results, thereby facilitating a more comprehensive approach to the treatment and management of this pathology.