Longitudinal assessment of urinary PCA3 for predicting prostate cancer grade reclassification in favorable-risk men during active surveillance.

BACKGROUND: To assess the utility of urinary prostate cancer antigen 3 (PCA3) as both a one-time and longitudinal measure in men on active surveillance (AS). METHODS: The Johns Hopkins AS program monitors men with favorable-risk prostate cancer with serial PSA, digital rectal examination (DRE), prostate magnetic resonance imaging and prostate biopsy. Since 2007, post-DRE urinary specimens have also been routinely obtained. Men with multiple PCA3 measures obtained over ⩾3 years of monitoring were included. Utility of first PCA3 score (fPCA3), subsequent PCA3 (sPCA3) and change in PCA3 were assessed for prediction of Gleason grade reclassification (GR, Gleason score >6) during follow-up. RESULTS: In total, 260 men met study criteria. Median time from enrollment to fPCA3 was 2 years (interquartile range (IQR) 1-3) and from fPCA3 to sPCA3 was 5 years (IQR 4-6). During median follow-up of 6 years (IQR 5-8), 28 men (11%) underwent GR. Men with GR had higher median fPCA3 (48.0 vs 24.5, P=0.007) and sPCA3 (63.5 vs 36.0, P=0.002) than those without GR, while longitudinal change in PCA3 did not differ by GR status (log-normalized rate 0.07 vs 0.06, P=0.53). In a multivariable model including age, risk classification and PSA density, fPCA3 remained significantly associated with GR (log(fPCA3) odds ratio=1.77, P=0.04). CONCLUSIONS: PCA3 scores obtained during AS were higher in men who underwent GR, but the rate of change in PCA3 over time did not differ by GR status. PCA3 was a significant predictor of GR in a multivariable model including conventional risk factors, suggesting that PCA3 provides incremental prognostic information in the AS setting.

Burn injuries from the london suicide bombings: a new classification of blast-related thermal injuries.

In July 2005, four suicide bombers detonated explosive improvised high explosive devices (IEDs) in three separate underground carriages and a double decker bus in London, resulting in 56 deaths and 775 injured. This study aims to understand the mechanisms and patterns of burn injuries from high explosives, and the related factors that determine mortality. The types and patterns of burn injuries in survivors and fatalities in the confined underground train carriages and the bus were analysed, evaluating injury severity score and the victims' relative position from the detonation point. The data were sourced from collated police witness statements, hospital records, forensic post mortem examinations and forensic examinations at the scene. The detonation of an explosive device in a confined space causes complex injuries to the human body, resulting in blast-related direct thermal and radiant burns. Injury patterns and mortality were related to crowd density, enclosure design, position of the victims and proximity to the device. Suicide bombings using IEDs will result in direct thermal burns and radiant burns currently categorised in the quaternary (miscellaneous) blast injury group. We propose a classification of these burns following an analysis of the London bombing data with respect to burns in both the fatalities and survivors. Distance from the device, crowd density and environment influences these burns.

En juillet 2005, 4 kamikazes faisaient exploser leur engin artisanal dans 3 rames de métro et 1 autobus à impériale de Londres, faisant 56 morts et 775 blessés. Cette étude a pour but d'étudier les mécanismes et la physiopathologie des brûlures liées à une explosion ainsi que d'évaluer les facteurs associés de mortalité. Nous avons analysé le type et la localisation des brûlures, l'ISS selon la position des victimes par rapport à l'épicentre. Les données provenaient des témoignages recueillis par les forces de police, des dossiers médicaux, des autopsies et des analyses de site. Une explosion en milieu clos entraînent des lésions complexes parmi lesquelles des brûlures thermiques directes et par radiation. La topographie des lésions et la mortalité étaient en relation avec la densité humaine, la topographie du volume clos, la position des victimes et leur situation par rapport à l'épicentre. Les brûlures directes et par radiation sont actuellement catégorisées dans les blasts quaternaires. A la suite des attentats londoniens, nous proposons une classification de ces brûlures, influencées par la distance à l'épicentre, la densité humaine et l'environnement.

40 years of terrorist bombings - A meta-analysis of the casualty and injury profile.

INTRODUCTION: Terrorists have used the explosive device successfully globally, with their effects extending beyond the resulting injuries. Suicide bombings, in particular, are being increasingly deployed due to the devastating effect of a combination of high lethality and target accuracy. The aim of this study was to identify trends and analyse the demographics and casualty figures of terrorist bombings worldwide. METHODS: Analysis of the Global Terrorism Database (GTD) and a PubMed/Embase literature search (keywords "terrorist", and/or "suicide", and/or "bombing") from 1970 to 2014 was performed. RESULTS: 58,095 terrorist explosions worldwide were identified in the GTD. 5.08% were suicide bombings. Incidents per year are increasing (P<0.01). Mean casualty statistics per incidents was 1.14 deaths and 3.45 wounded from non-suicide incidents, and 10.16 and 24.16 from suicide bombings (p<0.05). The kill:wounded ratio was statistically higher in suicide attacks than non-suicide attacks, 1:1.3 and 1:1.24 respectively (p<0.05). The Middle East witnessed the most incidents (26.9%), with Europe (13.2%) ranked 4th. The literature search identified 41 publications reporting 167 incidents of which 3.9% detailed building collapse (BC), 60.8% confined space (CS), 23.5% open space (OS) and 11.8% semi-confined space (SC) attacks. 60.4% reported on suicide terrorist attacks. Overall 32 deaths and 180 injuries per incident were seen, however significantly more deaths occurred in explosions associated with a BC. Comparing OS and CS no difference in the deaths per incident was seen, 14.2(SD±17.828) and 15.63 (SD±10.071) respectively. However OS explosions resulted in significantly more injuries, 192.7 (SD±141.147), compared to CS, 79.20 (SD±59.8). Extremity related wounds were the commonest injuries seen (32%). DISCUSSION/CONCLUSION: Terrorist bombings continue to be a threat and are increasing particularly in the Middle East. Initial reports, generated immediately at the scene by experienced coordination, on the type of detonation (suicide versus non-suicide), the environment of detonation (confined, open, building collapse) and the number of fatalities, and utilising the Kill:Wounded ratios found in this meta-analysis, can be used to predict the number of casualties and their likely injury profile of survivors to guide the immediate response by the medical services and the workload in the coming days.

Prophylaxis for blood-borne diseases during the London 7/7 mass casualty terrorist bombing: a review and the role of bioethics.

The suicide bombings in London on 7 July 2005 resulted in a mass casualty situation. Over 50% of casualties were treated at the Royal London Hospital where clinicians witnessed large numbers of severely injured patients. In some casualties human biological foreign material was found embedded in the soft tissue originating from the suicide bombers or other casualties. This had the potential of placing individuals at risk of transmission of blood-borne diseases. Advances in the fields of medicine and biology have led to increased survivorship in the context of trauma and mass casualty incidents. This has resulted in the emergence of ethical scenarios surrounding patient management. A systematic review of the literature of the 7/7 bombings, and suicide bombings reported globally, where biological implantation is noted, was performed to examine the medicolegal issues arising during such attack. Twelve casualties with human tissue implanted were recorded in the 7/7 bombings. While all patients at risk were given prophylaxis based on recommendations by the Health Protection Agency, several ethical considerations surfaced as a result. In this paper, we compare the sequence of events and the management process of the victims of the 7/7 bombings and the evidence-based research regarding blood-borne infection transmission. Furthermore, it explores the ethical dilemmas, experienced by the senior author on 7/7, surrounding prophylaxis for blood-borne diseases and protocols to avoid confusion over best practice in future bombing incidents.

Heterotopic ossification in victims of the London 7/7 bombings.

Heterotopic ossification (HO) is the formation of bone at extraskeletal sites. Over 60% of amputees injured by improvised explosive devices in the recent conflict in Afghanistan have developed HO, resulting in functional impairment. It is hypothesised that a key aetiological factor is the blast wave; however, other environmental and medical risk factors, which the casualties have been exposed to, have also been postulated. The suicide terrorist bombings in London in 2005 resulted in many blast-related casualties, many of whom were managed by the Royal London Hospital. This cohort of severely injured patients whose injuries also included trauma-related amputations shared some, but not all, of the risk factors identified in the military population. We reviewed these patients, in particular to assess the presence or absence of military-established risk factors for the formation of HO in these casualties.

An estimate of hernia prevalence in Sierra Leone from a nationwide community survey.

PURPOSE: A large number of unrepaired inguinal hernias is expected in sub-Saharan Africa where late presentation often results in incarceration, strangulation, or giant scrotal hernias. However, no representative population-based data are available to quantify the prevalence of hernias. We present data on groin masses in Sierra Leone to estimate prevalence, barriers to care, and associated disability. METHODS: A cluster randomized, cross-sectional household survey of 75 clusters of 25 households with 2 respondents each was designed to calculate the prevalence of and disability caused by groin hernias in Sierra Leone using a verbal head-to-toe examination. Barriers to hernia repairs were assessed by asking participants the main reason for delay in surgical care. RESULTS: Information was obtained from 3,645 respondents in 1,843 households, of which 1,669 (46%) were male and included in the study. In total, 117 males or 7.01% (95% CI 5.64-8.38) reported a soft or reducible swelling likely representing a hernia with four men having two masses. Of the 93.2% who indicated the need for health care, only 22.2% underwent a procedure, citing limited funds (59.0%) as the major barrier to care. On disability assessment, 20.2% were not able to work secondary to the groin swelling. CONCLUSIONS: The results indicate groin masses represent a major burden for the male population in Sierra Leone. Improving access to surgical care for adult patients with hernias and early intervention for children will be vital to address the burden of disease and prevent complications or limitations of daily activity.

Human body projectiles implantation in victims of suicide bombings and implications for health and emergency care providers: the 7/7 experience.

INTRODUCTION: On 7 July 2005 four suicide bombings occurred on the London transport systems. In some of the injured survivors, bone fragments were embedded as biological foreign bodies. The aim of this study was to revisit those individuals who had sustained human projectile implantation injuries as a result of the bomb blasts at all scenes, review the process of body parts mapping and DNA identification at the scene, detail the management of such injuries and highlight the protocols that have been put in place for protection against blood borne pathogens. METHODS: We retrospectively reviewed 12 instances of victims who sustained human body projectile implantation injuries. The Metropolitan Police and forensic scientists identified the human projectiles using DNA profiling and mapped these on the involved carriages and those found outside. All human projectiles included were greater than 3 cm(2). RESULTS: Twelve cases had human projectile implantation injuries. Of these, two died at the scene and ten were treated in hospital. Projectiles were mapped at three of the four bomb blast sites. Our findings show that victims within a 2m radius of the blast had human projectile injuries. Eight of the allogenic bony fragments that were identified in the survivors originated from the suicide bomber. All victims with an open wound should have prophylaxis against hepatitis B and serum stored for appropriate action against HIV and hepatitis C infection. CONCLUSIONS: All victims following a suicide bombing should be assumed to have human body projectile implantation injuries with blood products or bony fragments. All immediate care providers should receive prophylaxis against hepatitis B virus and appropriate action should be taken against HIV and hepatitis C infection.

Can urine dipstick testing for urinary tract infection at point of care reduce laboratory workload?

AIM: The University Hospitals of Leicester NHS Trust microbiology laboratory receives 150 000 urine samples each year, approximately 80% of which prove to be culture negative. The aim of this study was to reduce the proportion of culture negative urines arriving in the laboratory, by producing local evidence based guidelines for the use of urine dipstick testing at point of care within the trust's three acute hospitals. METHODS: One thousand and seventy six unborated urine samples were dipstick tested at the point of care using an automatic strip reader. Quantitative results for the four infection associated markers-leucocyte esterase, nitrite, blood, and protein-were compared with the results of conventional laboratory microscopy and culture. RESULTS: The performance of different marker combinations was calculated against the routine laboratory methods. One hundred and seventy five (16.3%) samples were negative for all four markers. Of these dipstick negative samples, only three (1.7% of all true positives) were positive by culture. The absence of all four infection associated markers was found to have a greater than 98% negative predictive value and a sensitivity and specificity of 98.3% and 19.2%, respectively. CONCLUSIONS: A urinary dipstick testing algorithm for infection associated markers was derived for use in hospital patients to screen out negative urines. Two years after distributing the algorithm and promoting access to reagent strips and strip readers, a reduction in the urine workload has been seen against an otherwise increasing laboratory specimen load.

Salvage of right colon interposition by microsurgical venous anastomosis.

Venous insufficiency of a right colon interposition in esophageal reconstruction can be a fatal complication resulting in total failure. A case is presented of the salvage of the right colon interposition by additional microsurgical venous anastomosis to relieve the problem of venous stasis. The outcome was successful in a young patient with a complicated medical history.

Large villous adenoma of the duodenum.

A 27-year-old man, who had symptoms of gastric outlet obstruction, was found on endoscopy to have a large duodenal polyp which on histology was diagnosed as villous adenoma. The tumor was resected surgically and the patient remained asymptomatic until two years later.

Unusual features of Helicobacter (Campylobacter) pylori--associated gastritis in India. A study of 200 cases.

Helicobacter (Campylobacter) pylori has been cultured from the antral biopsies of 85-90% of patients of gastritis, gastric ulcer and duodenal ulcer at different centres. Studies conducted all over the world have firmly implicated this organism in the aetiology of active superficial gastritis and recurrences of duodenal ulcer. Two hundred patients with upper abdominal pain, distension, vomiting and/or haemetemesis were subjected to OGD scopy. In 163 of these patients there was endoscopic evidence of gastritis; in 24 there was DU; in 3, GU and in 10 it was normal. Diagnosis of H pylori infection was made by the rapid biopsy urease test which is nearly 100% specific and 98% sensitive. 170 out of 200 patients were positive for H pylori. Among these were 138 patients of gastritis (84.6%); 22 cases of DU (91.6%); 2 cases of GU (66.6%) and 8 in whom endoscopy was normal. Histological examination of the antral biopsy specimens showed mild to severe infiltration of mucosa with lymphocytes and plasma cells. None of the 170 H pylori positive cases showed polymorphonuclear infiltration which has been stressed repeatedly by most Western authors to be characteristic of "active" superficial gastritis associated with H pylori infection. Even in those with a history of dyspepsia of barely 4 weeks duration or less there was no PMN infiltration in the mucosa. Thus the local response to infection by H pylori of the gastric mucosa is different in Indian patients.

Association of peptic ulcer with Helicobacter pylori and the recurrence rate. A three year follow-up study.

Helicobacter pylori is associated with 70-100% of peptic ulcers. Relapse of infection has been shown to cause recurrences of ulcers in a large number of studies. We diagnosed 137 cases of peptic ulcer (121 DU; 16 GU) during a 3 year period. Of these, 117 were positive for H pylori. Sixty six of the 117 cases staying in the vicinity of the Hospital were followed up for a minimum period of 3 months upto a maximum period of 3 years. In 91 examinations there was relapse of H pylori infection and ulcer recurrence was seen in 58 (63%), whereas ulcer recurred only in 6 out of 61 examinations where H pylori had not relapsed (10%). The difference was highly significant by Chi square test. (P less than 0.001).

Relapse of Helicobacter pylori infection after different treatment regimens. A 3-month follow-up study.

Helicobacter pylori infection of gastric antrum is associated with a majority of cases of peptic ulcer (70-100%). Studies have shown that when this organism is eradicated, the recurrence of ulcer falls to less than one-third of those in whom the infection persists or relapses. Monotherapy with bismuth salts, tinidazone or amoxycillin has been shown to result in early relapse and recurrence of ulcers. However, dual or triple therapy regimens are more effective. We conducted a randomised controlled study using tripotassium dicitrato bismuthate (TDB) (10 patients); amoxycillin (combined with ranitidine for ulcer healing) (9 patients) and dual therapy with both amoxycillin and TDB (10 patients). Our study showed that relapse rates at the end of 3 months was significantly less if dual therapy with TDB and amoxycillin is used as compared to TDB alone (p less than 0.05).

Double-blind comparison of the safety and efficacy of famotidine with ranitidine in patients with endoscopically diagnosed peptic ulcer.

In a double-blind randomised trial, 40 patients with active gastric or duodenal ulcer were treated with a single nocturnal dose of famotidine 40 mg or ranitidine 300 mg for 4 to 8 weeks. Antacid tablets were allowed as additional treatment, only if needed, for pain relief. Endoscopy was repeated after 4 weeks, and if the ulcer had not healed at 6 and/or 8 weeks. Relief of upper gastro intestinal symptoms with which the patient presented and the number of antacid tablets consumed, if any, were recorded on weekly basis. Two patients in famotidine group and 5 patients in ranitidine group did not complete the therapy and were considered dropouts. At the end of therapy, ulcers in 100% of the patients receiving famotidine & 93% of patients receiving ranitidine were healed. This difference was not statistically significant. Relief from ulcer related symptoms was rapid in both the groups. None of the patients in either group reported side effects. Overall opinion of investigator was comparable for both the treatments; however, significantly (P = 0.0334) larger proportion (100%) of patients from famotidine group rated it as an excellent therapy compared to only 73% from ranitidine group. Famotidine provides excellent healing of ulcers and early relief of upper gastrointestinal symptoms in Indian patients with peptic ulcer.

Congenital duodenal stenosis. The duodenal cervix sign.

A case of congenital duodenal stenosis is reported complicated by recurrent pancreatitis. The diagnosis was not initially entertained because of the pancreatitis. The radiographic appearance on gastrointestinal series was unusual for pancreatitis. The finding of an anomalous celiac axis on arteriography suggested the possibility of other congenital anomalies. The diagnosis of congenital duodenal stenosis was confirmed at laparotomy. The obstruction was relieved with a duodenojejunostomy. Two year follow-up reveals the patient to be asymptomatic without recurrence of pancreatitis. This is the first endoscopic report of this lesion and the presence of the duodenal cervix sign should suggest the diagnosis of congenital duodenal stenosis.