Testicular seminoma – unusual histology and staging with sub epithelial spread of seminoma along the vas deferans

BACKGROUND: The route of local and metastatic spread of testicular seminoma is well recognised and accepted. The spread is via lymphatics to the paraaortic nodes. CASE PRESENTATION: We present a case report of testicular seminoma in a 56 year old man with previously unreported histological findings. In this case seminoma tumour cells did not appear to have spread by the expected lymphatic route. There was no involvement of retro-peritoneal para-aortic lymph nodes. The tumour appeared to have spread directly along the vas deferans in the sub epithelial plane to the mesenteric lymph nodes. CONCLUSION: This type of seminoma tumour spread has not previously been described and it is not a recognised route for metastasis by seminoma tumour. In this case the macroscopic clinical appearance was of a stage I tumour with normal tumour markers. However, the pathological stage of the tumour was surprisingly increased to stage III on the basis of histology and CT radiological findings. We present the unusual histological findings. In view of this unusual histological finding we reinforce the need for accurate staging and for resection of the spermatic cord close to the deep inguinal ring. Accurate staging is crucial in planning the treatment and follow up of seminoma and determines the prognosis

Effects of gastroprotectant drugs for the prevention and treatment of peptic ulcer disease and its complications: a meta-analysis of randomised trials

Background: Gastroprotectant drugs are used for the prevention and treatment of peptic ulcer disease and might reduce its associated complications, but reliable estimates of the effects of gastroprotectants in different clinical settings are scarce. We aimed to examine the effects of proton-pump inhibitors (PPIs), prostaglandin analogues, and histamine-2 receptor antagonists (H2RAs) in different clinical circumstances by doing meta-analyses of tabular data from all relevant unconfounded randomised trials of gastroprotectant drugs. Background: Gastroprotectant drugs are used for the prevention and treatment of peptic ulcer disease and might reduce its associated complications, but reliable estimates of the effects of gastroprotectants in different clinical settings are scarce. We aimed to examine the effects of proton-pump inhibitors (PPIs), prostaglandin analogues, and histamine-2 receptor antagonists (H2RAs) in different clinical circumstances by doing meta-analyses of tabular data from all relevant unconfounded randomised trials of gastroprotectant drugs. Methods: We searched MEDLINE and Embase from Jan 1, 1950, to Dec 31, 2015, to identify unconfounded, randomised trials of a gastroprotectant drug (defined as a PPI, prostaglandin analogue, or H2RA) versus control, or versus another gastroprotectant. Two independent researchers reviewed the search results and extracted the prespecified outcomes and key characteristics for each trial. We did meta-analyses of the effects of gastroprotectant drugs on ulcer development, bleeding, and mortality overall, according to the class of gastroprotectant, and according to the individual drug within a gastroprotectant class. Findings: We identified comparisons of gastroprotectant versus control in 849 trials (142 485 participants): 580 prevention trials (110 626 participants), 233 healing trials (24 033 participants), and 36 trials for the treatment of acute upper gastrointestinal bleeding (7826 participants). Comparisons of one gastroprotectant drug versus another were available in 345 trials (64 905 participants), comprising 160 prevention trials (32 959 participants), 167 healing trials (28 306 participants), and 18 trials for treatment of acute upper gastrointestinal bleeding (3640 participants). The median number of patients in each trial was 78 (IQR 44·0–210·5) and the median duration was 1·4 months (0·9–2·8). In prevention trials, gastroprotectant drugs reduced development of endoscopic ulcers (odds ratio [OR] 0·27, 95% CI 0·25–0·29; p<0·0001), symptomatic ulcers (0·25, 0·22–0·29; p<0·0001), and upper gastrointestinal bleeding (0·40, 0·32–0·50; p<0·0001), but did not significantly reduce mortality (0·85, 0·69–1·04; p=0·11). Larger proportional reductions in upper gastrointestinal bleeding were observed for PPIs than for other gastroprotectant drugs (PPIs 0·21, 99% CI 0·12–0·36; prostaglandin analogues 0·63, 0·35–1·12; H2RAs 0·49, 0·30–0·80; phet=0·0005). Gastroprotectant drugs were effective in preventing bleeding irrespective of the use of non-steroidal anti-inflammatory drugs (phet=0·56). In healing trials, gastroprotectants increased endoscopic ulcer healing (3·49, 95% CI 3·28–3·72; p<0·0001), with PPIs more effective (5·22, 99% CI 4·00–6·80) than prostaglandin analogues (2·27, 1·91–2·70) and H2RAs (3·80, 3·44–4·20; phet<0·0001). In trials among patients with acute bleeding, gastroprotectants reduced further bleeding (OR 0·68, 95% CI 0·60–0·78; p<0·0001), blood transfusion (0·75, 0·65–0·88; p=0·0003), further endoscopic intervention (0·56, 0·45–0·70; p<0·0001), and surgery (0·72, 0·61–0·84; p<0·0001), but did not significantly reduce mortality (OR 0·90, 0·72–1·11; p=0·31). PPIs had larger protective effects than did H2RAs for further bleeding (phet=0·0107) and blood transfusion (phet=0·0130). Interpretation: Gastroprotectants, in particular PPIs, reduce the risk of peptic ulcer disease and its complications and promote healing of peptic ulcers in a wide range of clinical circumstances. However, this meta-analysis might have overestimated the benefits owing to small study bias

Bedside Availability of Prepared Oxytocin and Rapid Administration After Delivery to Prevent Postpartum Hemorrhage: An Observational Study in Karnataka, India

Postpartum hemorrhage is a leading cause of maternal death worldwide. Rapid provision of uterotonics after childbirth is recommended to reduce the incidence and severity of postpartum hemorrhage. Data obtained through direct observation of childbirth practices, collected in a study of the World Health Organization’s Safe Childbirth Checklist in Karnataka, India, were used to measure if oxytocin prepared for administration and available at the bedside before birth was associated with decreased time to administration after birth. This was an observational study of provider behavior: data were obtained during a baseline assessment of health worker practices prior to introduction of the Safe Childbirth Checklist, representing behavior in the absence of any intervention. Analysis was based on 330 vaginal deliveries receiving oxytocin at any point postpartum. Oxytocin was prepared and available at bedside for approximately 39% of deliveries. We found that advance preparation and bedside availability of oxytocin was associated with increased likelihood of oxytocin administration within 1 minute after delivery (adjusted risk ratio = 4.89, 95% CI = 2.61, 9.16), as well as with decreased overall time to oxytocin administration after delivery (2.9 minutes sooner in adjusted models, 95% CI = -5.0, -0.9). Efforts to reduce postpartum hemorrhage should include recommendations and interventions to ensure advance preparation and bedside availability of oxytocin to facilitate prompt administration of the medicine after birth

Celecoxib exerts protective effects in the vascular endothelium via COX-2-independent activation of AMPK-CREB-Nrf2 signalling

Although concern remains about the athero-thrombotic risk posed by cyclo-oxygenase (COX)-2-selective inhibitors, recent data implicates rofecoxib, while celecoxib appears equivalent to NSAIDs naproxen and ibuprofen. We investigated the hypothesis that celecoxib activates AMP kinase (AMPK) signalling to enhance vascular endothelial protection. In human arterial and venous endothelial cells (EC), and in contrast to ibuprofen and naproxen, celecoxib induced the protective protein heme oxygenase-1 (HO-1). Celecoxib derivative 2,5-dimethyl-celecoxib (DMC) which lacks COX-2 inhibition also upregulated HO-1, implicating a COX-2-independent mechanism. Celecoxib activated AMPKα(Thr172) and CREB-1(Ser133) phosphorylation leading to Nrf2 nuclear translocation. Importantly, these responses were not reproduced by ibuprofen or naproxen, while AMPKα silencing abrogated celecoxib-mediated CREB and Nrf2 activation. Moreover, celecoxib induced H-ferritin via the same pathway, and increased HO-1 and H-ferritin in the aortic endothelium of mice fed celecoxib (1000 ppm) or control chow. Functionally, celecoxib inhibited TNF-α-induced NF-κB p65(Ser536) phosphorylation by activating AMPK. This attenuated VCAM-1 upregulation via induction of HO-1, a response reproduced by DMC but not ibuprofen or naproxen. Similarly, celecoxib prevented IL-1β-mediated induction of IL-6. Celecoxib enhances vascular protection via AMPK-CREB-Nrf2 signalling, a mechanism which may mitigate cardiovascular risk in patients prescribed celecoxib. Understanding NSAID heterogeneity and COX-2-independent signalling will ultimately lead to safer anti-inflammatory drugs

Improving Adherence to Essential Birth Practices Using the WHO Safe Childbirth Checklist With Peer Coaching: Experience From 60 Public Health Facilities in Uttar Pradesh, India.

BACKGROUND: Adherence to evidence-based essential birth practices is critical for improving health outcomes for mothers and newborns. The WHO Safe Childbirth Checklist (SCC) incorporates these practices, which occur during 4 critical pause points: on admission, before pushing (or cesarean delivery), soon after birth, and before discharge. A peer-coaching strategy to support consistent use of the SCC may be an effective approach to increase birth attendants' adherence to these practices. METHODS: We assessed data from 60 public health facilities in Uttar Pradesh, India, that received an 8-month staggered coaching intervention from December 2014 to September 2016 as part of the BetterBirth Trial, which is studying effectiveness of an SCC-centered intervention on maternal and neonatal harm. Nurse coaches recorded birth attendants' adherence to 39 essential birth practices. Practice adherence was calculated for each intervention month. After 2 months of coaching, a subsample of 15 facilities was selected for independent observation when the coach was not present. We compared adherence to the 18 practices recorded by both coaches and independent observers. RESULTS: Coaches observed birth attendants' behavior during 5,971 deliveries. By the final month of the intervention, 35 of 39 essential birth practices had achieved >90% adherence in the presence of a coach, compared with only 7 of 39 practices during the first month. Key behaviors with the greatest improvement included explanation of danger signs, temperature measurement, assessment of fetal heart sounds, initiation of skin-to-skin contact, and breastfeeding. Without a coach present, birth attendants' average adherence to practices and checklist use was 24 percentage points lower than when a coach was present (range: -1% to 62%). CONCLUSION: Implementation of the WHO Safe Childbirth Checklist with coaching improved uptake of and adherence to essential birth practices. Coordination and communication among facility staff, as well as behaviors with an immediate, tangible benefit, showed the greatest improvement. Difficult-to-perform behaviors and those with delayed or theoretical benefits were less likely to be sustained without a coach present. Coaching may be an important component in implementing the Safe Childbirth Checklist at scale.Note: At the time of publication of this article, the results of evaluation of the impact of the BetterBirth intervention were pending publication in another journal. After the impact findings have been published, we will update this article on the effect of the intervention on birth practices with a reference to the impact findings

Lack of effect of lowering LDL cholesterol on cancer: meta-analysis of individual data from 175,000 people in 27 randomised trials of statin therapy

<p>Background: Statin therapy reduces the risk of occlusive vascular events, but uncertainty remains about potential effects on cancer. We sought to provide a detailed assessment of any effects on cancer of lowering LDL cholesterol (LDL-C) with a statin using individual patient records from 175,000 patients in 27 large-scale statin trials.</p> <p>Methods and Findings: Individual records of 134,537 participants in 22 randomised trials of statin versus control (median duration 4.8 years) and 39,612 participants in 5 trials of more intensive versus less intensive statin therapy (median duration 5.1 years) were obtained. Reducing LDL-C with a statin for about 5 years had no effect on newly diagnosed cancer or on death from such cancers in either the trials of statin versus control (cancer incidence: 3755 [1.4% per year [py]] versus 3738 [1.4% py], RR 1.00 [95% CI 0.96-1.05]; cancer mortality: 1365 [0.5% py] versus 1358 [0.5% py], RR 1.00 [95% CI 0.93–1.08]) or in the trials of more versus less statin (cancer incidence: 1466 [1.6% py] vs 1472 [1.6% py], RR 1.00 [95% CI 0.93–1.07]; cancer mortality: 447 [0.5% py] versus 481 [0.5% py], RR 0.93 [95% CI 0.82–1.06]). Moreover, there was no evidence of any effect of reducing LDL-C with statin therapy on cancer incidence or mortality at any of 23 individual categories of sites, with increasing years of treatment, for any individual statin, or in any given subgroup. In particular, among individuals with low baseline LDL-C (<2 mmol/L), there was no evidence that further LDL-C reduction (from about 1.7 to 1.3 mmol/L) increased cancer risk (381 [1.6% py] versus 408 [1.7% py]; RR 0.92 [99% CI 0.76–1.10]).</p> <p>Conclusions: In 27 randomised trials, a median of five years of statin therapy had no effect on the incidence of, or mortality from, any type of cancer (or the aggregate of all cancer).</p&gt

Survival from testicular cancer in England and Wales up to 2001

www.bjcancer.com For many years testicular cancer has been the prime example of the tumour that is chemocurable, even when metastatic. The disappointment in oncology is that these results have so far not been replicated in the more common solid tumours. Why this should be is not clear but germ-cell tumours retain sensitivity to chemotherapy in vitro and a number of mechanisms including reduced DNA repair capacity and proneness to apoptosis have been proposed (Mayer et al, 2003). Most patients with testicular cancer present after finding a lump in the testicle that may or may not be painful. A small proportion of patients present with symptoms of metastatic disease. With the exception of some patients with metastatic disease, initial treatment after first assessment is to remove the tumour by inguinal orchidectomy. Patients are staged by tumour marke

Initial steps towards an evidence-based classification system for golfers with a physical impairment

Purpose: The present narrative review aims to make a first step towards an evidence-based classification system in handigolf following the International Paralympic Committee (IPC). It intends to create a conceptual framework of classification for handigolf and an agenda for future research. Method: Pubmed was searched on three themes: “Classification in Paralympic sports”, “Performance determining factors in golf” and “Impact of impairments on golf performance”. IPC-regulations were gathered on the IPC-website and their official publications. Results: In developing a classification system conform IPC-regulations, the main challenge is to identify the activity limitation caused by the impairment, not influenced by training, talent or motivation. Timing, accuracy and control, work per joint, range of motion, balance and flexibility are important performance determining factors in abled-bodied golf and should be considered when determining activity limitations in handigolf. Only five articles on handigolf were found, mainly addressing the asymmetric golf movement. Based on the present review, a conceptual framework for classification was developed, while a future research agenda was designated. The conceptual framework presents factors that are essential for sports performance categorized under “technology”, “interface” and “athlete characteristics”. It also includes impairment related factors essential for determining eligibility and classification. Ideally, measures to be used during classification need to be resistant against training, natural development of the athlete’s talent and motivational changes. Conclusions: The conceptual framework and a multidimensional scientific research agenda will support further development of the knowledge base required for an evidence-based classification in handigolf, including multi-level analysis of player statistics, experimental analyses of biomechanics and modeling studies.Implications for Rehabilitation The main challenge in developing an evidence-based classification system conform IPC-regulations is defining eligibility criteria and sport classes based on activity limitation caused by only the impairment and not affected by training, talent and motivation. It is expected that a transparent classification system, a lively competition and admission to the Paralympic program will further promote participation in disabled golf. Timing, accuracy and control, work per joint, range of motion, balance and flexibility are of greater importance for golf performance in able-bodied golfers and expected to be of interest to incorporate in classification for handigolf. Side and level of amputation influence activity limitation in the asymmetric golf movement, and should be incorporated in classification. The proposed conceptual framework is fundamental to the research agenda that must further generate the knowledge-base to determine activity limitations caused by different impairments in handigolf and may serve as a guideline for other Paralympic sports in the development of evidence-based classification

Incidence, morbidity and mortality of patients with achalasia in England:findings from a study of nationwide hospital and primary care data

BackgroundAchalasia is an uncommon condition characterised by failed lower oesophageal sphincter relaxation. Data regarding its incidence, prevalence, disease associations and long-term outcomes are very limited.MethodsHospital Episode Statistics (HES) include demographic and diagnostic data for all English hospital attendances. The Health Improvement Network (THIN) includes the primary care records of 4.5 million UK subjects, representative of national demographics. Both were searched for incident cases between 2006 and 2016 and THIN for prevalent cases. Subjects with achalasia in THIN were compared with age, sex, deprivation tand smoking status matched controls for important comorbidities and mortality.ResultsThere were 10 509 and 711 new achalasia diagnoses identified in HES and THIN, respectively. The mean incidence per 100 000 people in HES was 1.99 (95% CI 1.87 to 2.11) and 1.53 (1.42 to 1.64) per 100 000 person-years in THIN. The prevalence in THIN was 27.1 (25.4 to 28.9) per 100 000 population. Incidence rate ratios (IRRs) were significantly higher in subjects with achalasia (n=2369) compared with controls (n=3865) for: oesophageal cancer (IRR 5.22 (95% CI: 1.88 to 14.45), p&lt;0.001), aspiration pneumonia (13.38 (1.66 to 107.79), p=0.015), lower respiratory tract infection (1.33 (1.05 to 1.70), p=0.02) and mortality (1.33 (1.17 to 1.51), p&lt;0.001). The median time from achalasia diagnosis to oesophageal cancer diagnosis was 15.5 (IQR 20.4) years.ConclusionThe incidence of achalasia is 1.99 per 100 000 population in secondary care data and 1.53 per 100 000 person-years in primary care data. Subjects with achalasia have an increased incidence of oesophageal cancer, aspiration pneumonia, lower respiratory tract infections and higher mortality. Clinicians treating patients with achalasia should be made aware of these associated morbidities and its increased mortality.</jats:sec