Brain connectomics predict response to treatment in social anxiety disorder.

We asked whether brain connectomics can predict response to treatment for a neuropsychiatric disorder better than conventional clinical measures. Pre-treatment resting-state brain functional connectivity and diffusion-weighted structural connectivity were measured in 38 patients with social anxiety disorder (SAD) to predict subsequent treatment response to cognitive behavioral therapy (CBT). We used a priori bilateral anatomical amygdala seed-driven resting connectivity and probabilistic tractography of the right inferior longitudinal fasciculus together with a data-driven multivoxel pattern analysis of whole-brain resting-state connectivity before treatment to predict improvement in social anxiety after CBT. Each connectomic measure improved the prediction of individuals' treatment outcomes significantly better than a clinical measure of initial severity, and combining the multimodal connectomics yielded a fivefold improvement in predicting treatment response. Generalization of the findings was supported by leave-one-out cross-validation. After dividing patients into better or worse responders, logistic regression of connectomic predictors and initial severity combined with leave-one-out cross-validation yielded a categorical prediction of clinical improvement with 81% accuracy, 84% sensitivity and 78% specificity. Connectomics of the human brain, measured by widely available imaging methods, may provide brain-based biomarkers (neuromarkers) supporting precision medicine that better guide patients with neuropsychiatric diseases to optimal available treatments, and thus translate basic neuroimaging into medical practice.

Evaluating cytology for the detection of invasive cervical cancer.

OBJECTIVE: To assess the sensitivity, the number needed to screen (NNS) and the positive predictive value (PPV) of cervical cytology for the diagnosis of cancer by age in a screening population. METHODS: A retrospective cohort of women with invasive cervical cancer nested within a census of cervical cytology. All (c. 8 million) women aged 20-64 years with cervical cytology (excluding tests after an earlier abnormality). From April 2007 to March 2010, 3372 women had cervical cancer diagnosed within 12 months of such cytology in England. The sensitivity of cervical cytology to cancer, NNS to detect one cancer and predictive values of cytology were calculated for various 'referral' thresholds. These were calculated for ages 20-24, 25-34, 35-49 and 50-64 years. RESULTS: The sensitivity of at least moderate dyskaryosis [equivalent to a high-grade squamous intraepithelial lesion (HSIL) or worse] for cancer of 89.4% [95% confidence interval (CI) 88.3-90.4%] in women offered screening was independent of age. At all ages, women with borderline-early recall or mild dyskaryosis on cytology (equivalent to ASC-US and LSIL, respectively, in the Bethesda system) had a similar risk of cervical cancer to the risk in all women tested. The PPV of severe dyskaryosis/?invasive and ?glandular neoplasia cytology (equivalent to squamous cell carcinoma and adenocarcinoma/adenocarcinoma in situ, respectively, in the Bethesda System) were 34% and 12%, respectively; the PPV of severe dyskaryosis (HSIL: severe dysplasia) was 4%. The NNS was lowest when the incidence of cervical cancer was highest, at ages 25-39 years, but the proportion of those with abnormal cytology who have cancer was also lowest in younger women. CONCLUSIONS: The PPV of at least severe dyskaryosis (HSIL: severe dysplasia) for cancer was 4-10% of women aged 25-64 years, justifying a 2-week referral to colposcopy and demonstrating the importance of failsafe monitoring for such patients. The sensitivity of cytology for cervical cancer was excellent across all age groups.

Is the increased risk of preterm birth following excision for cervical intraepithelial neoplasia restricted to the first birth post treatment?

OBJECTIVE: To explore whether the increased risk of preterm birth following treatment for cervical disease is limited to the first birth following colposcopy. DESIGN: Nested case-control study. SETTING: Twelve NHS hospitals in England. POPULATION: All nonmultiple births from women selected as cases or controls from a cohort of women with both colposcopy and a hospital birth. Cases had a preterm (20-36 weeks of gestation) birth. Controls had a term birth (38-42 weeks) and no preterm. METHODS: Obstetric, colposcopy and pathology details were obtained. MAIN OUTCOME MEASURES: Adjusted odds ratio of preterm birth in first and second or subsequent births following treatment for cervical disease. RESULTS: A total of 2798 births (1021 preterm) from 2001 women were included in the analysis. The risk of preterm birth increased with increasing depth of treatment among first births post treatment [trend per category increase in depth, categories <10 mm, 10-14 mm, 15-19 mm, ≥20 mm: odds ratio (OR) 1.23, 95% confidence interval (95% CI) 1.12-1.36, P < 0.001] and among second and subsequent births post treatment (trend OR 1.34, 95% CI 1.15-1.56, P < 0.001). No trend was observed among births before colposcopy (OR 0.98, 95% CI 0.83-1.16, P = 0.855). The absolute risk of a preterm birth following deep treatments (≥15 mm) was 6.5% among births before colposcopy, 18.9% among first births and 17.2% among second and subsequent births post treatment. Risk of preterm birth (once depth was accounted for) did not differ when comparing first births post colposcopy with second and subsequent births post colposcopy (adjusted OR 1.15, 95% CI 0.89-1.49). CONCLUSIONS: The increased risk of preterm birth following treatment for cervical disease is not restricted to the first birth post colposcopy; it remains for second and subsequent births. These results suggest that once a woman has a deep treatment she remains at higher risk of a preterm birth throughout her reproductive life.

Associated Inosine to interferon: results of a clinical trial in multiple sclerosis.

BACKGROUND: Uric acid (UA) could act as a natural peroxynitrite scavenger with antioxidant properties. It has been proposed that hyperuricemia might protect against multiple sclerosis (MS). METHODS: Patients with relapsing-remitting MS starting treatment with interferon beta-1a 44 µg sc 3/week were randomly assigned to receive either inosine 3 g/day or placebo in a double-blind manner. Follow-up was 12 months. Outcome measures were adverse events and UA laboratory results. Secondary end point was clinical and radiological activity of MS. Relapse rates, percentage of patients without relapses, and progression to secondary MS (SPMS) were assessed. RESULTS: Thirty six patients were included. Two patients in the inosine group showed UA serum level above 10 mg/ml, and symptoms derived from renal colic not leading to hospital admission. Ten additional patients had asymptomatic hyperuricemia (>7 mg). Efficacy parameters (clinical and radiological) were similar between groups. No patient progressed to SPMS CONCLUSIONS: Inosine administration was associated with hyperuricemia and renal colic with no additional effect on MS. We cannot conclude inosine is a safe and well-tolerated drug. Doses of around 2 g/day may be more appropriate for future trials.

Neuroimagen del linfoma primario del sistema nervioso central en pacientes inmunodeprimidos / Neuroimaging in immunodeficient patients with primary CNS lymphoma of the brain

Objetivos: El linfoma primario del sistema nervioso central (LPSNC) es una entidad rara con un pronóstico fatal. Dado el aumento en el número de casos con inmunosupresión adquirida, nuestros objetivos son estudiar las características epidemiológicas y neurorradiológicas de aquellos pacientes inmunodeprimidos con diagnóstico de LPSNC con afectación cerebral e investigar si existen diferencias entre los pacientes con el virus de la inmunodeficiencia humana (VIH) positivo y negativo.Materiales y métodos: Se realizó un estudio descriptivo y retrospectivo de los pacientes inmunodeprimidos con afectación cerebral por LPSNC, diagnosticados durante los últimos 13 años en 2 hospitales de referencia. Se evaluaron múltiples variables. El nivel de significación estadística utilizado fue p < 0,05.Resultados: El grupo VIH-positivo tenía una media de edad de 36,82 ± 5,4 años, frente a los55,60 ± 21,43 años de los pacientes VIH-negativo (p < 0,022). Los pacientes VIH-positivo tuvieron una media de 1,27 ± 0,65 lesiones por paciente, mientras que en el grupo VIH-negativo fue de 2,60 ± 1,78 (p < 0,039). El 18,2% (n = 2) del grupo VIH-positivo y el 80% (n = 8) del grupo VIH-negativo presentaron lesiones homogéneas (p < 0,005). Ningún paciente VIH-positivo tuvo afectación del cuerpo calloso, pero el grupo VIH-negativo presentó un 50% (n = 5) de afectación(p < 0,012).Conclusiones: El LPSNC en pacientes inmunodeprimidos puede presentar múltiples características en las imágenes. Existen diferencias entre los pacientes VIH positivo y negativo, por lo que es importante reconocerlas para establecer un manejo y tratamiento diferente entre ambos grupos.

Purposes: Primary central nervous system lymphoma (PCNSL) is a rare tumour with poor prognosis. Due to the increased number of patients with acquired immunodeficiency, our purposes are to describe epidemiological and imaging findings in immunodeficient patients with PCNSL of the brain and to study the differences between HIV-positive and HIV-negative patients with PCNSL.Materials and methods: A retrospective, descriptive study was performed with immunodeficient patients diagnosed of PCNSL of the brain during the last 13 years in two reference hospitals. Twenty-one patients fulfilled the inclusion criteria. Multiple variables were evaluated. Significance was defined as p<0.05.Results: HIV-positive group was a mean age of 36,82±5,4 years and the mean age in HIV-negative group was 55,60±21,43 years (p<0,022). The mean number of lesions was 1,27±0,65 in HIV-positive group and 2,60±1,78 in HIV-negative group (p<0,039). The lesions were homogeneous in 18,2% (n=2) HIV-positive group and 80% (n=8) in HIV-negative group (p<0,005). No HIV-positive patient and 50% (n=5) of HIV-negative patients showed corpus callosum involvement (p<0,012).Conclusions: PCNSL in immunodeficient patients is associated with a large spectrum of radiological findings. There were differences between HIV-positive and HIV-negative patients, is important recognize these differences as the therapeutic management of these two groups vary.

Benefits and harms of cervical screening from age 20 years compared with screening from age 25 years.

BACKGROUND: To quantify the benefits (cancer prevention and down-staging) and harms (recall and excess treatment) of cervical screening starting from age 20 years rather than from age 25 years. METHODS: We use routine screening and cancer incidence statistics from Wales (for screening from age 20 years) and England (screening from 25 years), and unpublished data from the National Audit of Invasive Cervical Cancer to estimate the number of: screening tests, women with abnormal results, referrals to colposcopy, women treated, and diagnoses of micro-invasive (stage 1A) and frank-invasive (stage IB+) cervical cancers (under three different scenarios) in women invited for screening from age 20 years and from 25 years. RESULTS: Inviting 100,000 women from age 20 years yields an additional: 119,000 screens, 20,000 non-negative results, 8000 colposcopy referrals, and an extra 3000 women treated when compared with inviting from age 25 years. Screening from age 20 years prevents between three and nine frank invasive cancers and between 0 and 23 cancers in total (depending on the scenario). A cumulative increase of nine stage IB+ cancers corresponds to an annual rate increase of 0.9 per 100,000 women aged 20-29 years. CONCLUSIONS: To prevent one frank invasive cancer, one would need to do between 12,500 and 40,000 additional screening tests in the age group 20-24 years and treat between 300 and 900 women.

[Rectal tonsil or lymphoid follicular hyperplasia of the rectum]. / Amígdala rectal o hiperplasia folicular linfoide del recto.

The rectal tonsil is a reactive proliferation of lymphoid tissue located in the rectum. The morphology of the lymphoid proliferation of the colon is usually polypoid or, less commonly, nodular. Only in exceptional cases does lymphoid proliferation of the colon present as a mass in the rectum (rectal tonsil), although this is the most common presentation in middle-aged patients. It is important to be familiar with the rectal tonsil because in cases of exuberant growth it can be difficult to distinguish it from other types of masses. We present the case of rectal tonsil in a four-year-old girl. We describe the magnetic resonance imaging findings and review the literature.

Characteristics and screening history of women diagnosed with cervical cancer aged 20-29 years.

BACKGROUND: There was concern that failure to screen women aged 20-24 years would increase the number of cancers or advanced cancers in women aged 20-29 years. We describe the characteristics of women diagnosed with cervical cancer in England aged 20-29 years and examine the association between the period of diagnosis, screening history and FIGO stage. METHODS: We used data on 1800 women diagnosed with cervical cancer between April 2007 and March 2012 at age 20-29 from the National Audit of Invasive Cervical Cancers. RESULTS: The majority of cancers (995, or 62% of those with known stage) were stage 1A. Cancer at age 20-24 years was rare (12% of those aged 20-29 years), when compared with age 25 (24%) and age 26-29 years (63%); however, cancers in women aged 20-24 years tended to be more advanced and were more often of a rare histological type. For 59% of women under age 30, the cervical cancer was screen detected, most of them (61%) as a result of their first screening test. A three-fold increase in the number of cancers diagnosed at age 25 years was seen since the start of the study period. CONCLUSION: Cervical cancer at age 20-24 years is rare. Most cancers in women under age 30 years are screen detected as microinvasive cancer.

Review of cytology and histopathology as part of the NHS Cervical Screening Programme audit of invasive cervical cancers.

OBJECTIVE: To audit pathology slide reporting in the Cervical Screening Programme in England by reviewing cytology and histology slides from women subsequently diagnosed with invasive cervical cancer. METHODS: Between April 2007 and March 2010, 6113 women diagnosed with cervical cancer were identified. Cervical cytology and histology slides taken within 10 years of diagnosis were identified and where possible reviewed after a nationally agreed protocol. Reviewers were not blinded to the original reading of each sample. Most cytology samples before 2005 were conventional, most after 2007 liquid based. RESULTS: Of 13,745 cytology results from women developing cervical cancer, 55% were reviewed. The review result was identical for 55% of slides. Of 3759 originally normal slides, only 45% were normal on review: 11% were inadequate, 21% low grade (borderline or mild dyskaryosis) and 23% high grade (moderate dyskaryosis or worse). Of tests originally normal taken over 5.5 years before diagnosis, 14% were upgraded to high grade compared with 37% within 3.5 years of diagnosis. Of 5159 histology specimens recorded within 10 years of diagnosis of a cancer, 3895 were reviewed. Overall, 94% of samples reviewed retained the original diagnosis. One per cent (33/3012) of cancers were downgraded and 5% (6/112) of negative samples were upgraded to cancer upon review (four of which were taken within 2 months of diagnosis). In comparison, 15% (14/91) of cervical glandular intraepithelial neoplasia (CGIN) and 12% (38/314) of cervical intraepithelial neoplasia grade 3 (CIN3) were upgraded to cancer. CONCLUSIONS: In spite of the excellent quality of cytology in England, a high proportion of negative cytology taken up to three and a half years before diagnosis were considered to contain abnormal cells by reviewers informed of the subsequent cancer. Continuing these reviews, with a strong focus on education, will ensure a clear understanding of these slides and further reduce the risk of developing cervical cancer.

Effect of diindolylmethane supplementation on low-grade cervical cytological abnormalities: double-blind, randomised, controlled trial.

BACKGROUND: Cervical screening identifies many women with low-grade abnormalities. In vitro and in vivo studies have shown that diindolylmethane (DIM) could potentially halt (cervical) carcinogenesis. We report on a randomised controlled trial of the effect of DIM in women with low-grade cervical cytological abnormalities. METHODS: We conducted a pragmatic double-blind, randomised controlled trial of 150 mg DIM (from BioResponse DIM) or placebo daily for 6 months in women with newly diagnosed, low-grade cytological abnormalities. Randomisation was in the ratio 2 (DIM) to 1 (placebo). All women were invited for colposcopy at 6 months with biopsy of any abnormality. RESULTS: Of the 551 randomised women available for analysis, 9% on DIM and 12% on placebo had cervical intraepithelial neoplasia-2 (CIN2) or worse after 6-month supplementation (risk ratio (RR) 0.7 (95% confidence interval (CI): 0.4-1.2)), whereas 4.6% and 5.1%, respectively, had CIN3 or worse (RR 0.9 (95% CI: 0.4-2.0)). A total of 27.3% of women on DIM and 34.3% on placebo had no sign of disease (negative cytology, colposcopy and human papilloma virus (HPV) tests) at 6 months (RR 0.8 (95% CI: 0.6-1.0)). Of those HPV-positive at baseline, 69% (114 out of 166) of the DIM group were positive at 6 months compared with 61% (43 out of 71) of the placebo group: RR 1.1 (95% CI: 0.9-1.4). Diindolylmethane supplementation was well tolerated. CONCLUSION: The results suggest that short-term DIM supplementation (150 mg day(-1)) is well tolerated, but is unlikely to have an effect on cytology or HPV infection. Uncertainty remains regarding its effect on CIN2+.

Predicted impact of vaccination against human papillomavirus 16/18 on cancer incidence and cervical abnormalities in women aged 20-29 in the UK.

BACKGROUND: Human papillomavirus (HPV) vaccination has been approved in more than 90 countries and is being implemented in many of these. In the UK, vaccination for girls aged 12-13 with catch-up for girls up to age 18 was introduced in 2008, using the bivalent GSK vaccine (Cervarix). METHODS: We modelled the proportion of abnormal smears, cervical intraepithelial neoplasia grade 3 (CIN3) and invasive cancer, which will be prevented in women aged 20-29 in the UK as a result of HPV vaccination. RESULTS: It will take many years for the full benefit of vaccination to be achieved. The earliest effects will be seen in women aged 20-29. With 80% coverage in women aged 12-13, we project an eventual 63% reduction in invasive cancer, a 51% reduction in CIN3 and a 27% reduction in cytological abnormalities before age 30. The full effect in this age group will not be seen until 2025, although half of the benefit will be seen by 2019 in England, where screening starts at age 25. However in Scotland and Wales, where screening starts at age 20, 50% of the benefit for CIN3 and abnormal smears (but not cancer) will be seen earlier. CONCLUSION: Substantial reductions in disease can be anticipated by vaccination, but most of the benefit will not be apparent for at least another decade. High vaccine coverage is the key factor for achieving these benefits.