A lysosomal enigma CLN5 and its significance in understanding neuronal ceroid lipofuscinosis.

Neuronal Ceroid Lipofuscinosis (NCL), also known as Batten disease, is an incurable childhood brain disease. The thirteen forms of NCL are caused by mutations in thirteen CLN genes. Mutations in one CLN gene, CLN5, cause variant late-infantile NCL, with an age of onset between 4 and 7 years. The CLN5 protein is ubiquitously expressed in the majority of tissues studied and in the brain, CLN5 shows both neuronal and glial cell expression. Mutations in CLN5 are associated with the accumulation of autofluorescent storage material in lysosomes, the recycling units of the cell, in the brain and peripheral tissues. CLN5 resides in the lysosome and its function is still elusive. Initial studies suggested CLN5 was a transmembrane protein, which was later revealed to be processed into a soluble form. Multiple glycosylation sites have been reported, which may dictate its localisation and function. CLN5 interacts with several CLN proteins, and other lysosomal proteins, making it an important candidate to understand lysosomal biology. The existing knowledge on CLN5 biology stems from studies using several model organisms, including mice, sheep, cattle, dogs, social amoeba and cell cultures. Each model organism has its advantages and limitations, making it crucial to adopt a combinatorial approach, using both human cells and model organisms, to understand CLN5 pathologies and design drug therapies. In this comprehensive review, we have summarised and critiqued existing literature on CLN5 and have discussed the missing pieces of the puzzle that need to be addressed to develop an efficient therapy for CLN5 Batten disease.

The impact of age and high-risk human papillomavirus (hrHPV) status on the prevalence of high-grade cervical intraepithelial neoplasia (CIN2+) in women with persistent hrHPV-positive, cytology-negative screening samples: a prospective cohort study.

OBJECTIVE: To establish the prevalence of high-grade cervical intraepithelial neoplasia (CIN2+) in women referred to colposcopy with persistent high-risk human papillomavirus (hrHPV) cytology-negative screening sample according to hrHPV genotype, age at referral and colposcopic performance. DESIGN: Prospective cohort study. SETTING: Single colposcopy clinic linked to a population-based screening programme. POPULATION: Women referred with persistent hrHPV cytology-negative routine screening samples. METHODS: Prospective study with descriptive statistics from a single colposcopy unit between June 2014 and July 2019. MAIN OUTCOME MEASURES: Prevalence of hrHPV genotypes and CIN2+, positive predictive value for colposcopic impression, and inadequate colposcopic examinations. RESULTS: A total of 3107 women were referred. Prevalence of CIN2+ was highest for persistent HPV16 infections (10.7%) compared with HPV18 (3.6%) or HPVO (4.7%). Prevalence of CIN2+ declined with age (25-34 years 14.2% to 55-64 years 1.1%) whereas the percentage of women with an inadequate colposcopic examination increased (25-34 years 0.9% to 55-64 years 29.5%). High-grade colposcopic impression fell over time during the study from 16.1 to 5.1%. The positive predictive value for colposcopic impression of CIN2+ was affected by hrHPV genotype (57.3% for HPV16 versus 32.1% for nonHPV16). The adjunctive use of electrical impedance spectroscopy detected an extra 42 cases of CIN2+, which was irrespective of hrHPV genotype. CONCLUSIONS: Primary hrHPV cervical screening increases detection of CIN2+; however, low specificity results in more women being referred to colposcopy with a low prevalence of CIN2+. Colposcopy performs poorly in some groups, particularly with HPVO infections and women over 50 years of age. An appropriate threshold for referral to colposcopy in primary hrHPV screening has not been established. TWEETABLE ABSTRACT: Low prevalence of CIN2+ in HPV-positive negative cytology samples. HPV genotype, age and prevalence of CIN2+ affect colposcopic performance.

Electric Rydberg-Atom Interferometry.

An electric analogue of the longitudinal Stern-Gerlach matter-wave interferometer has been realized for atoms in Rydberg states with high principal quantum number n. The experiments were performed with He atoms prepared in coherent superpositions of the n=55 and n=56 circular Rydberg states in a zero electric field by a π/2 pulse of resonant microwave radiation. These atoms were subjected to a pulsed inhomogeneous electric field to generate a superposition of momentum states before a π pulse was applied to invert the internal states. The same pulsed inhomogeneous electric field was then reapplied for a second time to transform the motional states to have equal momenta before a further π/2 pulse was employed to interrogate the final Rydberg state populations. This Hahn-echo microwave pulse sequence, interspersed with a pair of equivalent inhomogeneous electric field pulses, yielded two spatially separated matter waves. Interferences between these matter waves were observed as oscillations in the final Rydberg state populations as the amplitude of the pulsed electric field gradients was adjusted.

Prevalence of high-grade cervical intraepithelial neoplasia in women with persistent high-risk HPV genotypes and negative cytology.

INTRODUCTION: Primary HPV screening will be implemented into the English Cervical Screening Programme by 2019. Its impact upon women referred to colposcopy, with negative cytology but persistently positive high-risk HPV (hrHPV), remains unreported from UK Sentinel sites. HPV primary screening was introduced in Sheffield, UK in April 2013; this paper reports its impact on the service. METHODS: A retrospective cohort study was performed from June 2014 to July 2016 at the Jessop Wing Colposcopy Unit, Sheffield. UK. Data were obtained from the pathology and colposcopy databases and cross-referenced with case-notes and pathology results for women referred with persistently positive hrHPV, cytology negative samples. Patient demographics, hrHPV genotype, biopsy rates, histological diagnoses, management, and outcomes were collected and baseline statistics performed. RESULTS: During the study 1076 women were seen. Most frequent hrHPV genotypes were: hrHPV other, 41%; and HPV16, 33%. The majority (72%) were found to have normal colposcopy; 28% had an abnormal colposcopic assessment (11% low-grade; 11% high-grade; 6% inadequate). The majority were discharged (83%) and only 5% underwent LLETZ. No cancers were detected. High-grade cervical intraepithelial neoplasia (CIN) was found in 7%; overall risk of CIN2 was 1/29; 1/30 for CIN3. Presence of HPV16 was associated with a significantly higher risk of high-grade CIN; 1/9. CONCLUSION: This is the first study to report results for women referred to colposcopy with cytology negative, persistently positive hrHPV. Disease prevalence is low, although women with HPV16 have a significantly higher likelihood of high-grade disease compared to other HPV subtypes.

Influence of a triclosan toothpaste on periodontopathic bacteria and periodontitis progression in cardiovascular patients: a randomized controlled trial.

BACKGROUND AND OBJECTIVE: Triclosan/copolymer toothpaste is effective in controlling plaque and gingivitis and in slowing the progression of periodontitis. This study describes its influence on microbiological and clinical outcomes, over a 5-year period, in patients with established cardiovascular disease (CVD). MATERIAL AND METHODS: Four-hundred and thirty-eight patients were recruited from the Cardiovascular Unit at The Prince Charles Hospital, Brisbane, Australia, and randomized to triclosan or placebo groups. Six sites per tooth were examined annually for probing pocket depth and loss of attachment. These outcomes were analysed, using generalized linear modelling, in 381 patients who had measurements from consecutive examinations. Concurrent load of the periodontal pathogens Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum, Tannerella forsythia and Porphyromonas gingivalis was determined, using quantitative real-time PCR, in 437 patients with baseline plaque samples. Group comparisons were expressed as geometric means. The chi-square test was used to test for differences between the two groups of patients with regard to the proportion of patients with different numbers of bacterial species. RESULTS: There was no difference in general health or periodontal status between the groups at baseline. There was a significant reduction in the number of interproximal sites showing loss of attachment between examinations, by 21% on average (p < 0.01), in the triclosan group compared with the placebo group. The prevalence of patients with F. nucleatum and A. actinomycetemcomitans was high and remained relatively constant throughout the 5 years of the study. In contrast, the prevalence of T. forsythia and P. gingivalis showed more variability; however, there was no significant difference between the groups, at any time point, in the prevalence of any organism. A significant difference in the geometric means for P. gingivalis (p = 0.01) was seen at years 1 and 4, and for F. nucleatum (p = 0.01) and in the total bacterial load (p = 0.03) at year 2; however, these differences were not statistically significant following a Bonferroni correction for multiple comparisons. There was no difference between the groups in the geometric means for each organism at year 5. CONCLUSION: Within the limitations of the study, these data suggest that the use of triclosan/copolymer toothpaste significantly slowed the progression of periodontitis in patients with CVD but that it had little influence on key subgingival periodontopathic bacteria in these patients over the 5 years of the study.

Does LLETZ excision margin status predict residual disease in women who have undergone post-treatment cervical cytology and high-risk human papillomavirus testing?

OBJECTIVE: This study looks at the importance of large loop excision of the transformation zone (LLETZ) excision margins and residual cervical intraepithelial neoplasia (CIN) in women undertaking high-risk human papillomavirus (hrHPV) test of cure (TOC). METHODS: A retrospective cohort study with interval analysis performed June 2007 and June 2012 on all women undertaking treatment for CIN and subsequent hrHPV TOC 6 months post LLETZ. RESULTS: Final analysis group comprised 2093 women treated by LLETZ (1396 completely excised; 697 incompletely excised). 298 out of 1794 women (13%) were hrHPV positive at TOC. Thirty-six women who failed TOC and attended colposcopy had residual CIN. No statistically significant difference existed between the completely and incompletely excised groups with regards to the detection of residual CIN at 6 months post-treatment. There was no correlation of margins of excision with hrHPV status at TOC. The overall cure rate at TOC was 98%. CONCLUSIONS: TOC pathways recommend subsequent follow-up in primary care. This study identified no safety issues with TOC pathways. We can no longer assess histological failure rates at 12 months; we, therefore, recommend that this measure of treatment failure be redefined for post TOC women. It seems time to question the benefits of routine excision margins reporting, in the absence of invasion, for treated CIN. Future reporting needs to be reconsidered by the Royal College of Pathologists.

A national audit of standards of care for women with vulval conditions and survey of attitudes to nurse practitioners in vulval services in the UK.

This national audit assessed whether UK specialist vulval clinics adhere to the British Society of Vulval Diseases (BSSVD) document 'Standards of care for women with vulval conditions' published in 2013 and benchmarked clinician attitudes towards nurse practitioners in vulval services. Audit standards were based on the BSSVD guidance. All BSSVD and British Society for Colposcopy and Cervical Pathology or BSCCP members were surveyed via two electronic questionnaires. Results demonstrate that the majority of specialist vulval clinics in the UK are non-compliant with the standards set out for specialist vulval services. The majority of clinicians would support the introduction of clinical nurse specialists to vulval services, but there is need for development of a national training programme. In conclusion, significant improvements are required in provision of patient information, guidelines, access to multidisciplinary services, multidisciplinary team or MDT processes and data recording in UK specialist vulval services.

High-risk HPV platforms and test of cure: should specific HPV platforms more suited to screening in a 'test of cure' scenario be recommended?

OBJECTIVE: When the Sheffield screening laboratory changed the high-risk human papillomavirus (hrHPV) platforms from hybrid capture 2(®) (HC2; Digene Ltd) and to cobas 4800(®) (Roche) an unexpected and substantial increase in the number of cytology-negative/hrHPV-positive test-of-cure (ToC) samples after large loop excision of the transformation zone (LLETZ) was noted. We explore the potential reasons for these increased rates and discuss the implications this may have on the English NHS cervical screening programme (CSP). METHODS: A retrospective cohort study with interval analysis between June 2007 and June 2012. RESULTS: ToC was performed on 1530 women with HC2 and 396 with cobas 4800: 95.1% and 92.4% of women had negative cytology at ToC in the HC2 and cobas4800 testing period, respectively. Of these 13.9% and 27.8% tested positive for hrHPV in the HC2 and cobas 4800 group, respectively (P = <0.0001). No clinically significant increase in the number of cases of cervical intraepithelial neolpasia (CIN) was detected by the cobas4800 test in spite of doubling the number of cytology-negative/hrHPV-positive ToC samples. CONCLUSIONS: As far as we are aware, this is the first study reporting potential differences between different HPV platforms currently available in the English programme. The immediate impact of this increase in rates of hrHPV detection with cobas4800 is an increased number of colposcopy referrals to our service. The NHSCSP needs to assess whether this increase is acceptable and, if not, whether specific HPV platforms more suited to screening in a ToC scenario should be recommended.

The multidisciplinary colposcopy meeting: recommendations for future service provision and an analysis of clinical decision making.

OBJECTIVE: In 2004 the NHS Cervical Screening Programme (NHSCSP) recommended that multidisciplinary meetings should be incorporated into patient management. No data has been provided since then regarding its functionality or benefits. We aim to address this issue. DESIGN: Retrospective review. SETTING: Jessop Wing colposcopy multidisciplinary meeting (MDM), Sheffield, UK. POPULATION: All women referred to the MDM from September 2003 to September 2009. METHODS: Retrospective review of the colposcopy database (Sept 2003-Sept 2009), cross-referenced with multidisciplinary team (MDT) letters, patient notes and the hospital results reporting system. Baseline statistics were used for data analysis. MAIN OUTCOME MEASURES: Indications for MDT referral; concordance rates from cytopathology and histopathology review; concordance rates between MDT treatment decisions and final patient management. RESULTS: A total of 535 cases were discussed at 62 MDT meetings during the allocated study period. Discrepancy between referral cytology and cervix punch biopsy was the most common referral (49%). Cytology and histology review concurred with the initial reports in 75.8 and 97.8% of cases, respectively; the MDT decision was concordant with the final patient management in 97% of cases. The main reason for discordance (67%) resulted from patient factors. CONCLUSIONS: When significant discrepancies exist between colposcopy, cytology and histopathology, then MDT discussion seems pertinent as MDT discussion can lead to the avoidance of over-treatment. To improve timeliness of treatment, MDT meetings should occur at least monthly. The results of each case discussion should be recorded in the patient case notes, the minutes of each meeting should be circulated to all MDT members and a letter describing MDT recommendations must be sent to the colposcopist responsible for patient care.

Association of blood lactate concentration and outcome in foals.

BACKGROUND: Lactate concentration in blood or plasma ([LAC]) and change in [LAC] are associated with survival in sick foals. HYPOTHESIS: [LAC] and change in [LAC] over time are associated with survival at 96 hours and discharge in neonatal foals. Furthermore [LAC] and change in [LAC] over time correlate with blood culture results and blood pressure at admission. ANIMALS: Two hundred and twenty-five foals consecutively admitted to a Neonatal Intensive Care Unit. METHODS: Retrospective case review. Foals

Prospective evaluation of coagulation in critically ill neonatal foals.

BACKGROUND: Coagulopathy is a potentially underrecognized complication of sepsis and septic shock in critically ill neonatal foals. HYPOTHESIS: Critically ill neonatal foals have abnormalities in coagulation that are associated with disease severity and outcome. ANIMALS: Foals <72 hours old admitted to a neonatal intensive care unit. METHODS: Prospective, observational study. Blood was collected at admission, 24, and 48 hours for platelet count, prothrombin time, activated partial thromboplastin time, antithrombin activity and concentrations of fibrin degradation products, and fibrinogen in plasma from all foals. RESULTS: Sixty-three foals were enrolled and classified as Septic Shock (12), Septic (28), and Other (23). At least 1 abnormal value was found in 18/28 (64%) samples from the Septic Shock group, 66/85 (78%) from the Septic group, and 30/59 (51%) from the Other group (P= .01). Coagulopathy (3 or more abnormal values) was present in 7/28 (25%) samples in the Septic Shock group, 14/85 (16%) samples in the Septic group, and 3/59 (5%) samples in the Other group (P= .0028). Clinically detectable bleeding occurred in 8/12 (67%) Septic Shock cases, 11/28 (39%) Septic cases, and 3/23 (13%) Other cases (P= .009). Foals in Septic Shock were 12.7 times more likely to have clinical evidence of bleeding than those in the Other group (95% CI 2.3-70, P= .004). Treatment with fluids or plasma did not have a detectable effect on coagulation values. CONCLUSIONS AND CLINICAL IMPORTANCE: Coagulopathy commonly occurs in critically ill neonatal foals, especially those with sepsis and septic shock.

Diagnostic challenges in extrauterine epithelioid trophoblastic tumours: a report of two cases.

INTRODUCTION: Epithelioid trophoblastic tumour (ETT) is a rare condition with a paucity of cases reported in the literature. CASE REPORTS: We present two unusual cases of ETT. Both patients presented with markedly elevated hCG levels; one case presented with a mass in the gallbladder, the other with extensive metastases; and both patients died from disease. DISCUSSION: To gain a greater understanding of the nature and progression of this disease, reporting of cases in the literature should be thorough and contain detailed information on patient clinicopathological characteristics and treatment. To enable identification of prognostic factors, long-term follow up must also be reported because recurrence can be both late and complex.

Progression of periodontal disease and interleukin-10 gene polymorphism.

BACKGROUND AND OBJECTIVE: Interleukin-10 is a key immunoregulatory cytokine that may be of significance in the immunopathogenesis of chronic inflammatory diseases such as periodontal disease. Molecular genetic studies have defined a number of haplotypes that may be associated with differing levels of interleukin-10 secretion. The present study investigated the possible association between interleukin-10 gene polymorphism and periodontal disease progression. MATERIAL AND METHODS: Genomic DNA was obtained from 252 adults who were part of a prospective longitudinal study on the progression of periodontal disease in a general adult Australian population. Single nucleotide polymorphisms at positions -592 and -1082 in the interleukin-10 promoter were analysed using an induced heteroduplex methodology and used to determine interleukin-10 promoter haplotypes in individual samples. Periodontitis progression was assessed by measuring probing depths and relative attachment levels at regular intervals over a 5-year period. A generalized linear model was used to analyse the data, with age, gender, smoking status, interleukin-1 genotype and Porphyromonas gingivalis included as possible confounders. RESULTS: There was a significant (p approximately 0.02) main effect of interleukin-10 haplotypes, with individuals having either the ATA/ACC or the ACC/ACC genotype experiencing around 20% fewer probing depths of >or= 4 mm compared to individuals with other genotypes. Age and smoking had significant (p < 0.001) additional effects. CONCLUSION: These data suggest that the interleukin-10 genotype contributes to the progression of periodontal disease.

P53 and bcl-2 assessment in serous ovarian carcinoma.

The study objective was to determine the prognostic value of assessment of staining of p53 and bcl-2 in a well-selected group of serous ovarian carcinomas. Immunohistochemical detection was used to identify both p53 and bcl-2 positive tumors. One hundred thirty-two tumors were analyzed for positivity of staining, grade of staining intensity, and for p53 alone, percent expression rates. These were analyzed alongside traditional clinicopathologic parameters for their ability to predict overall survival (OS), disease-free survival (DFS), and response to chemotherapy (CR). Univariate COX analysis revealed percent p53 expression (P = 0.012) and p53 grade (P = 0.01) to be significant predictors of DFS. Neither the p53 nor bcl-2 measurement parameters were found significant for OS or prediction of CR. On multivariate analysis, incorporating clinicopathologic parameters, p53 parameters did not retain independent significance for any outcome measure. As in primary reported studies, bcl-2 was not found to be of clear independent prognostic value in this group of ovarian tumors. If mutation of p53 and its consequent overexpression is an early event in ovarian tumorigenesis, then p53 assessment may prove useful prognostically in the assessment of either low-grade ovarian carcinomas, as a possible indicator for progression, or in early-stage ovarian tumors, as a marker of tumor aggression or likelihood of recurrence. p53 analysis of a larger group of stage I ovarian tumors would be desirable to further explain the potential association with DFS.

The prognostic value of nuclear morphometric analysis in serous ovarian carcinoma.

The objective of this study was to determine whether nuclear morphometric data can predict survival, disease progression, and chemotherapeutic response in ovarian serous carcinoma. Nuclear morphometric parameters were determined from archival hematoxylin and eosin sections of 132 serous tumors. Clinicopathologic and morphometric parameters were evaluated as to their individual and independent prognostic value and prediction of chemotherapy response. Nuclear parameters were found to strongly correlate with extent of disease residuum, tumor grade, and FIGO stage. Univariate analysis revealed stage, grade, preoperative CA125, presence of ascites, extent of disease residuum, standard deviation of nuclear area (SDNA), nuclear perimeter (NP), SDNP, nuclear length (NL), nuclear breadth (NB), orthoferet, and equivalent diameter (ED) to be significant predictors of overall survival (OS) and disease-free survival (DFS). Grade, stage, extent of disease residuum, presence of ascites, SDNA, NP, NL, NB, and orthoferet were found to be significant predictors of chemotherapy response. Multivariate analysis revealed extent of disease residuum (P

A 5-year longitudinal study of Tannerella forsythia prtH genotype: association with loss of attachment.

BACKGROUND: Tannerella forsythia (previously T. forsythensis) in subgingival plaque has been recognized as a defined periodontal pathogen, but its mere presence may be insufficient for disease initiation and/or progression. The organism may produce a cysteine protease, encoded by the prtH gene, which may play a role in the transition from commensal organism to opportunistic pathogen. This study aimed to relate changes in the level of T. forsythia prtH genotype over a 5-year period to a concomitant loss of attachment. METHODS: Real-time polymerase chain reaction was used to quantify the level of the prtH gene in plaque samples from subjects with and without attachment loss (> or =2 mm in at least two sites) over a 5-year period. Clinical measures and subgingival plaque samples were obtained at yearly intervals. RESULTS: Baseline levels of the prtH genotype were significantly lower in the subjects without loss of attachment compared to those who lost attachment over 1, 2, 4, or 5 years. In the subjects with loss of attachment, the higher prtH levels at baseline were not maintained until the end of the observation period. CONCLUSION: Higher levels of the prtH genotype were associated significantly with future attachment loss.

Bacteremia in equine neonatal diarrhea: a retrospective study (1990-2007).

BACKGROUND: Bacteremia in sick foals is associated with survival, but the association of bacteremia and diarrhea is not reported. HYPOTHESIS: Neonatal foals with diarrhea will commonly be bacteremic. ANIMALS: One hundred and thirty-three neonatal foals. METHODS: Records of all foals <30 days of age presenting with diarrhea between January 1990 and September 2007 were reviewed. RESULTS: Sixty-six of 133 foals (50%) were bacteremic at admission, with 75 isolates from the 66 samples. The blood culture from a further 18 foals (13.5%) grew coryneform bacteria. Nine foals (6.8%) had 2 or more organisms grown on blood culture. One foal had 5 different organisms, interpreted as contamination. Forty-eight foals (36%) had no growth on admission blood cultures. No cultures isolated fungal organisms. Excluding coryneform bacteria, 43 isolates (57%) were Gram-negative organisms and 32 isolates (43%) were Gram-positive organisms. The most common isolate was Enterococcus spp. (22 isolates, 29%), followed by Pantoea agglomerans (13 isolates, 17%). IgG concentration at admission was not associated with blood culture status. Blood culture status was not associated with survival to hospital discharge. CONCLUSIONS AND CLINICAL IMPORTANCE: Bacteremia is common in neonatal foals with diarrhea. Decisions regarding antimicrobial selection should be made with these differences in mind.

Retrospective study of dystocia in mares at a referral hospital.

REASONS FOR PERFORMING STUDY: The period between the onset of dystocia and its resolution has an important bearing on fetal outcome. There are few published data on which to base decisions regarding optimum management of cases in practice. OBJECTIVES: To evaluate and compare the effects of a coordinated dystocia management protocol (CDMP) with that of a previous protocol of random management on time to resolution and outcome in both an emergency dystocia referral population of mares (referred emergency cases: EM) and in a population of mares residing in hospital due to high risk pregnancy (HRP) concerns that then experience dystocia at parturition. METHODS: Retrospective study performed at a university hospital referral centre of cases presenting from 1991-2004 divided into Group 1 (pre-CDMP) and Group 2 (CDMP). RESULTS: Medical records of 71 cases with dystocia were retrieved and data recorded. For referred emergency cases (EM), time from hospital presentation to resolution decreased significantly by 32 min (P = 0.03) after institution of CDMP. Survival rate of mares at discharge was 86%. Survival of EM foals was low, with 10% in Group 1 and 13% in Group 2, surviving to discharge. For EM foals delivered alive, survival to discharge was 30% and 43% in Groups 1 and 2, respectively. Median Stage II was significantly (P < 0.001) different at 71 and 282 min for EM foals delivered alive vs. those not alive at delivery, respectively. Median duration of Stage II was also significantly (P < 0.001) different between EM foals surviving and not surviving to discharge, at 44 and 249 min, respectively. Survival of HRP dystocia foals to discharge was 79%. CONCLUSIONS: Although CDMP reduced the time from presentation at the hospital to resolution significantly for EM, total duration of Stage II for EM was unchanged, as was foal outcome. POTENTIAL RELEVANCE: Very early referral of mares with dystocia to referral centres with dystocia management protocols may improve fetal outcome as increased duration of Stage II in the horse affects fetal outcome negatively.

Classification systems in Gestational trophoblastic neoplasia - Sentiment or evidenced based?

The classification system for Gestational trophoblastic neoplasia (GTN) has proved a controversial topic for over 100years. Numerous systems simultaneously existed in different countries, with three main rival classifications gaining popularity, namely histological, anatomical and clinical prognostic systems. Until 2000, prior to the combination of the FIGO and WHO classifications, there was no worldwide consensus on the optimal classification system, largely due to a lack of high quality data proving the merit of one system over another. Remarkably, a validated, prospectively tested classification system is yet to be conducted. Over time, increasing criticisms have emerged regarding the currently adopted combined FIGO/WHO classification system, and its ability to identify patients most likely to develop primary chemotherapy resistance or disease relapse. This is particularly pertinent for patients with low-risk disease, whereby one in three patients are resistant to first line therapy, rising to four out of five women who score 5 or 6. This review aims to examine the historical basis of the GTN classification systems and critically appraise the evidence on which they were based. This culminates in a critique of the current FIGO/WHO prognostic system and discussion surrounding clinical preference versus evidence based practice.