Selective intradural dorsal rhizotomy for persistent radicular leg pain: a contemporary series

Publication date: Available online 6 July 2018

Source: The Spine Journal

Author(s): Sierk H. Bakker, Niels A. van der Gaag, Godard C.W. de Ruiter, Mark P. Arts

Abstract

Background

Lumbar disc surgery for radicular leg pain is one of the most frequently performed spine procedures. In approximately 20% of patients poor outcome is achieved. The most complex cases have persistent leg pain without residual nerve root compression. Treatment for refractory cases is limited to medical pain management, spinal cord stimulation (SCS) and dorsal root ganglion stimulation (DRGS). For the latter two, fair to good results are obtained in only 50% of patients and costs and complication rates are high. An alternative surgical procedure is selective intradural dorsal rhizotomy (SIDR). This procedure has been largely abandoned, likely due to poor historic results and readily available modern alternatives.

Purpose

The goal of this paper is to report our results for SIDR for persistent monoradicular leg pain without residual nerve root compression and to compare the results to those of SCS.

Study design

Prospectively followed case series.

Patient sample

Consecutive patients with persistent monoradicular leg pain without residual nerve root compression.

Outcome measures

Visual Analogue Scale for leg pain, Roland Disability Questionnaire and Likert Scale for leg pain were recorded. Complications were documented and patients were asked if, in retrospect, they would undergo the procedure again.

Methods

In Haaglanden Medical Center, SIDR was performed on 8 consecutive patients with persistent monoradicular leg pain without residual nerve root compression between December 2013 and September 2017. Patients were followed prospectively and VAS for leg pain, Roland Disability Questionnaire and Likert Scale for leg pain were recorded at intake, 8 weeks and 1 year after surgery and yearly after that. Minimal clinically important differences (MCID) for VAS and RDQ were predefined. Means and ranges were calculated and due to the small sample size further analysis was limited to descriptive analysis.

Results

Mean follow-up was 20 months. VAS for leg pain improved from 80mm at intake to 34mm at latest follow-up. Five out of 8 patients (63%) had good Likert Scale outcome (complete or near complete recovery of leg pain). Patients scored 19,5 on the Roland Disability Questionnaire at intake and 12,7 at the end of follow-up. Four patients (57%) reached a MCID for VAS at 1 year post surgery and 1 reached borderline MCID. Five patients (71%) reached a MCID for RDQ at 1 year post surgery. Six patients (75%) would undergo the procedure again.

Conclusions

SIDR is a safe and effective procedure in strictly selected patients with persistent monoradicular leg pain without residual nerve root compression. Considering the high costs and complication rates of SCS, the results of this study warrant a randomized controlled trial comparing the cost-effectiveness of SIDR and SCS.

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Nonoperative Management of Perforated Hollow Viscera in a Palliative Care Unit

No abstract available

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Ten-year Outcomes of a Prospective Randomized Trial of Laparoscopic Gastric Bypass Versus Laparoscopic Gastric Banding

Objective: The primary endpoints of this study were long-term weight loss, morbidity, and changes in comorbidities and quality of life. Background: Bariatric surgery is an effective option for the treatment of severe obesity and its related comorbidities. However, few studies have reported on the long-term outcome (>5 yrs) of bariatric surgery. Methods: Between 2002 and 2007, 250 patients with a body mass index (BMI) of 35 to 60 kg/m2 were randomly assigned to undergo laparoscopic gastric bypass or laparoscopic gastric banding. After exclusions, 111 patients underwent gastric bypass and 86 patients underwent gastric banding. Factors predictive of improved weight loss were analyzed using multiple logistic regressions. Results: At baseline, the mean age was 43 ± 10 years and the mean BMI was 46.5 ± 5.6 kg/m2. At 10-year follow-up, the mean total body weight loss for the entire cohort was −37.5 ± 19.4 kg, −42.4 ± 19.6 kg for gastric bypass versus −27.4 ± 14.5 kg for gastric banding. Late reoperation was significantly higher after gastric banding compared with the gastric bypass group (31.4% vs. 8.1%, respectively, P

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Incidence of Adhesive Bowel Obstruction After Colon Cancer Surgery and its Risk Factors: A Nationwide Claim Study

Objective: To elucidate the incidence of adhesive postoperative bowel obstruction (PBO) after colon cancer surgery and its risk factors using nationwide claim data. Background: PBO has a significant impact on quality of life and medical costs after colectomy, though most of the literature consists of single-institution analyses. Methods: Data from 24,645 patients who underwent regional colectomy for colon cancer from 2010 to 2012 and had at least 3 years of follow up were obtained from the Health Insurance Review and Assessment Service database. Patients who required nasogastric tube insertion or bowel obstruction surgery more than 30 days after index colectomy were defined as having PBO. Results: A total of 3083 (12.5%) patients experienced at least one PBO episode within 3 years after surgery. Logistic regression analysis showed that significant risk factors for PBO were elderly (odds ratio, OR = 1.13), male (OR = 1.27), open colectomy (OR = 1.99), and low-volume institution (OR = 1.17). Among 3083 PBO patients, 50.7% experienced their 1st PBO during the 1st year after the index colectomy, and 7.8% experienced recurrence within 3 years after index colectomy. The 3-year cumulative incidences of PBO according to risk factors of elderly, male, open colectomy, and low-volume institution were 14.6%, 14.3%, 19.5%, and 15.1%, respectively. Conclusions: We report several independent risk factors for PBO and its incidence after regional colectomy for colon cancer. These results are informative for medical providers as patients who will or have had the procedure and could be useful baseline data for further research on the active prevention or treatment of PBO after colectomy.

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Small-world indices via network efficiency for brain networks from diffusion MRI

Abstract

The small-world architecture has gained considerable attention in anatomical brain connectivity studies. However, how to adequately quantify small-worldness in diffusion networks has remained a problem. We addressed the limits of small-world measures and defined new metric indices: the small-world efficiency (SWE) and the small-world angle (SWA), both based on the tradeoff between high global and local efficiency. To confirm the validity of the new indices, we examined the behavior of SWE and SWA of networks based on the Watts–Strogatz model as well as the diffusion tensor imaging (DTI) data from 75 healthy old subjects (aged 50–70). We found that SWE could classify the subjects into different age groups, and was correlated with individual performance on the WAIS-IV test. Moreover, to evaluate the sensitivity of the proposed measures to network, two network attack strategies were applied. Our results indicate that the new indices outperform their predecessors in the analysis of DTI data.

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Malignant granular cell tumor of the median nerve: a case report with a literature review of 157 cases

Abstract

Malignant granular cell tumors are an extremely rare, high-grade sarcoma with a schwannian phenotype and are composed of malignant granular cells with cytoplasmic lysosomal inclusion. To date, 157 cases of malignant granular cell tumors have been reported. We report the first case of a malignant granular cell tumor arising from the digital nerve to the median nerve in the palm, and we review the 157 previously reported cases and summarize the clinical profile, treatment, and outcome of this tumor. The median age, tumor size, and follow-up periods were 51 years, 6 cm, and 24 months respectively. With respect to the oncological result, 53 patients (33.8%) had no evidence for disease, 31 (19.7%) were alive with the disease, and 51 (32.5%) died because of the disease. Our case report indicates that rare malignant tumors can arise from the digital nerve to the median nerve in the palm, an anatomical site that is usually affected by benign lesions. Exhaustive discussions between surgeons and pathologists are necessary for the treatment of this rare malignant tumor.

https://ift.tt/2lWGo16

Cancers, Vol. 10, Pages 225: Geriatric Assessment in Older Patients with Acute Myeloid Leukemia

Cancers, Vol. 10, Pages 225: Geriatric Assessment in Older Patients with Acute Myeloid Leukemia

Cancers doi: 10.3390/cancers10070225

Authors: Kah Poh Loh Heidi D. Klepin

The incidence of acute myeloid leukemia (AML) increases with age, but the outcomes for older adults with AML are poor due to underlying tumor biology, poor tolerance to aggressive treatment, and the physiologic changes of aging. Because of the underlying heterogeneity in health status, treatment decisions are difficult in this population. A geriatric assessment (GA) refers to the use of various validated tools to assess domains that are important in older adults including physical function, cognition, comorbidities, polypharmacy, social support, and nutritional status. In older patients with cancer, a GA can guide treatment decision-making, predict treatment toxicity, and guide supportive care interventions. Compared to solids tumors, there is a relative lack of studies evaluating the use of a GA in older patients with AML. In this review, we will discuss the principles, common domains, feasibility, and benefits of GA, with a focus on older patients with AML that includes practical applications for clinical management.

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Surgical management of chronic genital lymphoedema

A 44-year-old man with a spinal cord injury was referred to a specialist urology service with a 7-year history of significant genital swelling. His condition had eluded diagnosis and was refractory to all previous treatments. The considerable swelling both impacted his quality of life and prevented the patient from adequately managing his neurogenic bladder. He was diagnosed with chronic idiopathic genital lymphoedema and underwent total scrotectomy, wide penile skin excision and split skin graft to the penile shaft. The patient made an excellent recovery. We present this unusual case with preoperative, intraoperative and postoperative images.

https://ift.tt/2IYmQlX

Case of hepatic portal venous gas in an infant with hypertrophic pyloric stenosis

Hepatic portal venous gas is the presence of gas within the portal vein and its branches. A 4-week-old male infant presented with 1-week history of non-bloody, non-bilious projectile emesis. Examination was significant for an olive-shaped mass in the abdomen. Bloodwork showed hypokalaemic metabolic alkalosis. Abdominal ultrasound and radiograph was significant for portal venous gas and did not meet radiographic criteria for pyloric stenosis. He underwent upper endoscopy, which showed a narrowed, hypertrophic pylorus. The child underwent pyloromyotomy with resolution of his emesis. Hepatic portal venous gas (HPVG) is very rare and can be seen in the setting of hypertrophic pyloric stenosis. It is believed that an increase in intraluminal dilation and pressure subsequently moves gas from the intestinal mucosa venous system and lymphatics into the portal veins. The presence of HPVG in a well-appearing patient can be benign and should not prompt further testing nor delay treatment.

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Renal cell carcinoma with level 2 IVC thrombus

Description

A 40-year-old male patient, a chronic smoker for the last 10 years, presented with oedema of the lower legs and gross painless haematuria of 2 months duration. He also gave history of weight loss and loss of appetite. Physical examination revealed a right abdominal mass. Complete blood haemogram was normal. A comprehensive metabolic evaluation including serum calcium levels, C-reactive protein, liver function and urinalysis was also found normal.

Multidetector CT scan showed a right renal tumour of size 8x8 cm involving upper and mid-pole with tumour thrombus extending from the renal vein (RV) into the infrahepatic inferior vena cava (IVC) (figure 1). CT angiography was further performed to confirm the vascularity and extent of RV thrombus as shown in figure 2.

Figure 1

Right renal cell carcinoma involving upper and mid-pole with tumour thrombus extending into infrahepatic inferior vena cava (IVC).

...

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CMV encephalitis in an immune-competent patient

After being admitted to hospital with atypical chest pain, a 61-year-old woman was noted to become lethargic and confused. She also developed global dysphasia. MRI was suggestive of encephalitis, and lumbar puncture was positive for cytomegalovirus (CMV) PCR. The patient was treated with intravenous ganciclovir and subsequent oral valganciclovir and she gradually made a reasonable recovery. While this infection is usually closely linked to immunosuppression, the patient was found to be HIV negative, and was not on any immunosuppressive therapy. Going through the patient's medical history revealed two possible risk factors which might have led to the development of CMV encephalitis: immunosuppression secondary to underlying poorly controlled diabetes mellitus; and previous admission to the intensive care unit which might have lead to CMV reactivation.

https://ift.tt/2KVUxGD

Monosomy 7 in Pediatric Myelodysplastic Syndromes

Myelodysplastic syndromes (MDS) in children and adolescents are a rare heterogeneous group of clonal stem cell disorders. Complete or partial loss of chromosome 7 constitutes the most common cytogenetic abnormality encountered in any type of childhood MDS, is associated with more advanced disease, and usually requires a timely allogeneic stem cell transplantation. This article provides insights into the current understanding of the genotype, phenotype, and clonal evolution patterns in pediatric MDS associated with loss of chromosome 7.

https://ift.tt/2lUSk3k

Introduction to Acquired and Inherited Bone Marrow Failure

Acquired aplastic anemia and inherited bone marrow failure syndromes both present with pancytopenia and must be distinguished because they have differences in treatment decisions and continued monitoring requirements. Advances in the genetic interrogation of patient samples have led to identification of inherited germline diseases and appreciation that patients with inherited bone marrow failure disorders may be normal in appearance with few expected clinical clues. Somatic mutations in aplastic anemia may have prognostic value. Hematopoietic stem cells from inherited marrow failure diseases can correct the proliferative defect and may develop further somatic mutations that progress to myelodysplastic syndrome or acute myeloid leukemia.

https://ift.tt/2zbLErm

Copyright

ELSEVIER

https://ift.tt/2lUGMNH

Acquired and Inherited Bone Marrow Failure Syndromes

Acquired aplastic anemia (AA) and inherited bone marrow failure syndromes (IBMFS) are rare disorders characterized by the failure of production of mature erythrocytes, leukocytes, and platelets by the bone marrow. Pancytopenia is the usual presentation of acquired AA, while the inherited diseases may predominantly affect one or more lineages and variably evolve into broad hematopoietic failure. AA has usually been considered a consequence of an abnormal immune response to infectious or toxic agents such as drugs or chemicals.

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Contents

Colin A. Sieff

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Bone Marrow Failure

HEMATOLOGY/ONCOLOGY CLINICS OF NORTH AMERICA

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Forthcoming Issues

Waldenström Macroglobulinemia

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Contributors

GEORGE P. CANELLOS, MD

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Myelodysplastic Syndrome, Acute Myeloid Leukemia, and Cancer Surveillance in Fanconi Anemia

Fanconi anemia (FA) is a DNA repair disorder associated with a high risk of cancer and bone marrow failure. Patients with FA may present with certain dysmorphic features, such as radial ray abnormalities, short stature, typical facies, bone marrow failure, or certain solid malignancies. Some patients may be recognized due to exquisite sensitivity after exposure to cancer therapy. FA is diagnosed by increased chromosomal breakage after exposure to clastogenic agents. It follows autosomal recessive and X-linked inheritance depending on the underlying genomic alterations. Recognizing patients with FA is important for therapeutic decisions, genetic counseling, and optimal clinical management.

https://ift.tt/2lWmfs4

Effects of therapeutic play on children undergoing cast-removal procedures: a randomised controlled trial

Objectives

To examine (1) the effectiveness of therapeutic play in reducing anxiety and negative emotional manifestations among children undergoing cast-removal procedures and (2) the satisfaction of parents and cast technicians with cast-removal procedures.

Design

A randomised controlled trial.

Setting

An orthopaedic outpatient department of a regional teaching hospital in Hong Kong.

Participants

Children (n=208) aged 3–12 undergoing cast-removal procedure were invited to participate.

Interventions

Eligible children were randomly allocated to either the intervention (n=103) or control group (n=105) and stratified by the two age groups (3–7 and 8–12 years). The intervention group received therapeutic play intervention, whereas the control group received standard care only. Participants were assessed on three occasions: before, during and after completion of the cast-removal procedure.

Outcome measures

Children's anxiety level, emotional manifestation and heart rate. The satisfaction ratings of parents and cast technicians with respect to therapeutic play intervention were also examined.

Results

Findings suggested that therapeutic play assists children aged 3–7 to reduce anxiety levels with mean differences between the intervention and control group was –20.1 (95% CI –35.3 to –4.9; p=0.01). Overall, children (aged 3–7 and 8–12) in the intervention groups exhibited fewer negative emotional manifestations than the control group with a mean score difference –2.2 (95% CI –3.1 to –1.4; p<0.001). Parents and technicians in the intervention group also reported a higher level of satisfaction with the procedures than the control group with a mean score difference of 4.0 (95% CI –5.6 to 2.3; p<0.001) and 2.6 (95% CI 3.7 to 1.6; p<0.001), respectively.

Conclusion

Therapeutic play effectively reduces anxiety and negative emotional manifestations among children undergoing cast-removal procedures. The findings highlight the importance of integrating therapeutic play into standard care, in particular for children in younger age.

Trial registration number

ChiCTR-IOR-15006822; Pre-results.

https://ift.tt/2MRm64x

Impact of social relationships on income-laughter relationships among older people: the JAGES cross-sectional study

Objectives

Laughter has a positive and quantifiable effect on certain aspects of health, and previous studies have suggested that income influences the emotion. However, it is unknown whether social relationship-related factors modify the association between equivalised income and laughter among older people. In the present study, we examined the relationship between equivalised income and the frequency of laughter. In addition, we examined the impact of social relationship-related factors on the association between equivalised income and frequency of laughter using a cross-sectional study design.

Design

Cross-sectional study and binomial regression analysis.

Setting

We sampled from 30 municipalities in Japan.

Participants

We examined 20 752 non-disabled Japanese individuals aged ≥65 years using data from the Japan Gerontological Evaluation Study.

Primary outcome

Frequency of laughter.

Results

Laughter increased significantly with an increase in equivalent income (p for trend <0.0001). Prevalence ratios (PR) for laughing almost every day were calculated according to quartile equivalised income after adjusting for age, instrumental activities of daily living, depression, frequency of meeting friends, number of social groups and family structure. The results revealed that PRs in Q4 (men; ≥24 420, women; ≥21 154) were 1.21 (95% CI 1.13 to 1.30) among men and 1.14 (95% CI 1.08 to 1.20) among women, as compared with Q1 (men; <12 041, women; <9518), respectively. After excluding participants with depression, the association remained significant. In addition, we found inadequate social relationships and living alone were associated with a lower frequency of laughter. In comparison with the lowest equivalent income with meeting friends less frequently and living alone, the PRs of the highest equivalent income with meeting friends frequently and living with someone were higher, respectively.

Conclusions

The results revealed a significant relationship between equivalent income and the frequency of laughter. Social relationships and family structure were also associated with the frequency of laughter.

https://ift.tt/2KT4uI6

Sexual behaviours and sexual health outcomes among young adults with limiting disabilities: findings from third British National Survey of Sexual Attitudes and Lifestyles (Natsal-3)

Objective

To explore whether the sexual behaviours and sexual health outcomes of young adults with self-reported disabilities that they perceive limit their activities ('limiting disability') differ from those without disability.

Design

Complex survey analyses of cross-sectional probability sample survey data collected between September 2010 and August 2012 using computer-assisted personal interviewing and computer-assisted self-interview.

Setting

British general population.

Participants

7435 women and men aged 17–34 years, resident in private households in Britain, interviewed for the third National Survey of Sexual Attitudes and Lifestyles.

Main outcome measures

Self-reported sexual behaviour and sexual health outcomes.

Results

Approximately 1 in 10 participants reported having a limiting disability. Sexual behaviours were similar between those with limiting disability and those without, with a few exceptions. Women and men with limiting disability were less likely to report having sexual partner(s) (past year, adjusted ORs (AORs) for age and social class: AORs: 0.71, 0.75, respectively). Women with limiting disability were more likely to report having same-sex partner(s) in the past 5 years (AOR: 2.39). Differences were seen in sexual health outcomes, especially among women; those with limiting disability were more likely to report having experienced non-volitional sex (ever, AOR: 3.08), STI diagnoses (ever, AOR: 1.43) and sought help/advice regarding their sex life (past year, AOR: 1.56). Women with limiting disability were also more likely to feel distressed/worried about their sex life than those without limiting disability (AORs: 1.61). None of these associations were seen in men.

Conclusions

Young adults with limiting disability, especially women, are more likely to report adverse sexual health outcomes than those without, despite comparatively few behavioural differences. It is important to ensure that people with disabilities are included in sexual health promotion and service planning, and targeted policy and programme interventions are needed to address negative sexual health outcomes disproportionally experienced by people with disabilities.

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Integrating culturally informed approaches into physiotherapy assessment and treatment of chronic pain: a pilot randomised controlled trial

Objective

To evaluate patient engagement with, and the feasibility of, a novel, culturally adapted physiotherapy pain management approach.

Design

A participant-blinded and assessor-blinded pilot randomised controlled trial.

Setting

Outpatient physiotherapy departments at two public hospitals and one district pain clinic.

Participants

Adults (n=48) with chronic musculoskeletal pain (daily pain >3 months), who self-identified as Mandaean, Assyrian or Vietnamese, were randomised to one of two physiotherapy treatment conditions.

Interventions

24 participants underwent combined group and individualised treatment described as 'culturally adapted physiotherapy', while 24 underwent evidence-informed 'usual physiotherapy care'. Both treatment arms consisted of up to 10 sessions over a 3-month period.

Outcome measures

Patient engagement was measured via participant attendance, adherence and satisfaction data. Secondary outcomes included clinical measures of pain severity, interference and suffering, physical function and negative emotional state.

Results

96% of participants undergoing culturally adapted physiotherapy completed treatment, compared with 58% of the usual physiotherapy group. For the culturally adapted group attendance (87%±18%) and adherence (68%±32%) were higher relative to usual care (68%±32% and 55%±43%). Satisfaction was similar for the culturally adapted (82.7%±13.4%) and usual care (79.3±17.3) groups. For secondary outcomes, a significant between-group effect for pain-related suffering in favour of the culturally adapted group was observed with a medium effect size (partial ² 0.086, mean 3.56, 95% CI 0.11 to 7), while results for pain severity, interference, physical function and negative emotional state were similar.

Conclusions

Aligning treatment with the beliefs and values of culturally and linguistically diverse communities enhances patient engagement with physiotherapy. These results support the feasibility of a larger, multisite trial to determine if improved engagement with culturally adapted physiotherapy translates to improved clinical outcomes.

Trial registration number

ACTRN12616000857404; Pre-results.

https://ift.tt/2KT49VQ

Cardiovascular mortality in a Western Asian country: results from the Iran Cohort Consortium

Objectives

Cardiovascular mortality in Western Asia is high and still rising. However, most data documented on risk prediction has been derived from Western countries and few population-based cohort studies have been conducted in this region. The current study aimed to present the process of pooling data and cardiovascular disease (CVD) mortality incidences for four Iranian cohorts.

Methods

From the Iran Cohort Consortium, the Golestan Cohort Study (GCS), Tehran Lipid and Glucose Study, Isfahan Cohort Study (ICS) and the Shahroud Eye Cohort Study (ShECS) were eligible for the current study since they had appropriate data and follow-up visits. Age-standardised CVD mortality rates were estimated for ages 40–80 and 40–65 years. Cox regression was used to compare mortalities among cohorts. Adjusted marginal rates were calculated using Poisson regression.

Results

Overall, 61 291 participants (34 880 women) aged 40–80 years, free of CVD at baseline, were included. During 504 606 person-years of follow-up, 1981 CVD deaths (885 women) occurred. Age-standardised/sex-standardised premature CVD mortality rates were estimated from 133 per 100 000 person-years (95% CI 81 to 184) in ShECS to 366 (95% CI 342 to 389) in the GCS. Compared with urban women, rural women had higher CVD mortality in the GCS but not in the ICS. The GCS population had a higher risk of CVD mortality, compared with the others, adjusted for conventional CVD risk factors.

Conclusions

The incidence of CVD mortality is high with some differences between urban and rural cohorts in Iran as a Western Asian country. Pooling data facilitates the opportunity to globally evaluate risk prediction models.

https://ift.tt/2MRXQ2k

Rationale and design of the improving Care for Cardiovascular Disease in China (CCC) project: a national registry to improve management of atrial fibrillation

Introduction

Inadequate management of patients with atrial fibrillation (AF) has been reported in China for anticoagulation therapy and treatment for concomitant diseases. An effective quality improvement programme has been lacking to promote the use of evidence-based treatments and improve outcome in patients with AF.

Methods and analysis

The Improving Care for Cardiovascular Disease in China-AF programme is a collaboration of the American Heart Association and the Chinese Society of Cardiology. This programme is designed to promote adherence to AF guideline recommendations and outcomes for inpatients with AF. Launched in February 2015, 150 hospitals are recruited by geographic-economic regions across 30 provinces in China. Each month, 10–20 inpatients with AF are enrolled in each hospital. A web-based data collection platform is used to collect clinical information for patients with AF, including patients' demographics, admission information, medical history, in-hospital care and outcomes, and discharge medications for managing AF. The quality improvement initiative includes monthly benchmarked reports on hospital quality, training sessions, regular webinars and recognitions of hospital quality achievement. Primary analyses will include adherence to performance measures and guidelines. To address intrahospital correlation, generalised estimating equation models will be applied. As of March 2017, 28 801 AF inpatients have been enrolled.

Ethics and dissemination

This study protocol was approved by the Ethics Committee of Beijing Anzhen Hospital, Capital Medical University. Results will be published in peer-reviewed medical journals.

Trial registration number

NCT02309398.

https://ift.tt/2KyCqup

Protocol of the randomised placebo controlled pilot trial of the management of acute sciatica (SCIATICA): a feasibility study

Introduction

Acute sciatica (symptom duration less than 4 weeks), a major cause of pain and disability, is a common presentation to medical practices and hospital emergency departments. Selective CT fluoroscopy transforaminal epidural steroid injection is often used with the hope of reducing pain and improving function. Recently, there has been interest in using systemic corticosteroids in acute sciatica. However, there is limited evidence to inform management of selective CT fluoroscopy transforaminal epidural steroid in subacute and chronic sciatica and there is no evidence in acute sciatica, even though the practice is widespread. There is also limited evidence for the use of systemic corticosteroids in acute sciatica. Furthermore, the management of selective CT fluoroscopy transforaminal epidural steroid versus systemic steroids has never been directly studied.

Methods and analysis

SCIATICA is a pilot/feasibility study of patients with acute sciatica designed to evaluate the feasibility of undertaking a blinded four-arm randomised controlled intervention study of (1) selective CT fluoroscopy transforaminal epidural steroid (arm 1), (2) selective CT fluoroscopy transforaminal epidural saline (arm 2), (3) 15 days tapering dose of oral steroids (arm 3) and (4) a sham epidural and oral placebo control (arm 4). This feasibility study is designed to evaluate head-to-head, route versus pharmacology of interventions. The primary outcome measure is the Oswestry Disability Index (ODI) at 3 weeks. Secondary outcome is the ODI at 48 weeks. Other outcomes include numerical rating scale for leg pain, Pain DETECT Questionnaire, quality of life, medication use, rescue procedures or surgery, and adverse events. Results of outcomes from this randomised controlled trial will be used to determine the feasibility, sample size and power calculations for a large multicentre study.

Ethics and dissemination

The study has been approved by South Eastern Sydney Local Health District Human Research Ethics Committee (HREC/15/331/POHW/586).

Trial registration number

NCT03240783; Pre-results.

https://ift.tt/2MRXMj6

Lifestyle, socioeconomic status and healthcare seeking among women with gynaecological cancer alarm symptoms: a combined questionnaire-based and register-based population study

Objectives

To determine the proportion of contacts to general practitioner (GP) with recent onset gynaecological cancer alarm symptoms (pelvic pain, postmenopausal bleeding, bleeding during intercourse or pain during intercourse) and to analyse the associations between lifestyle factors, socioeconomic status and GP contact for these symptoms.

Design

Cross-sectional survey combined with data from national registers.

Setting

The general Danish population.

Participants

A total of 25 866 non-pregnant women ≥20 years completed the survey. Women reporting at least one of four gynaecological alarm symptoms within the preceding 6 months form the study base (n=2957).

Results

The proportion of women reporting GP contact ranged from 21.1% (pain during intercourse) to 32.6% (postmenopausal bleeding). Women aged 60+ years had higher odds of reporting GP contact for at least one of the four gynaecological cancer alarm symptoms compared with those aged 20–39 years (OR 2.56, 95% CI 1.69 to 3.89), and immigrants had higher odds of reporting GP contact for at least one of the symptoms (OR 1.56, 95% CI 1.13 to 2.15) compared with ethnic Danish individuals. Among those reporting postmenopausal bleeding and/or bleeding during intercourse, women in the age group 60+ years had higher odds of reporting GP contact compared with those aged 20–39 years (OR 2.79, 95% CI 1.33 to 5.87). A high educational level (>12 years) was positively associated with reporting GP contact for postmenopausal bleeding and/or bleeding during intercourse compared with a low educational level (<10 years) (OR 2.23, 95% CI 1.19 to 4.19). No associations were found with lifestyle factors.

Conclusions

Few women contacted their GP with recent onset gynaecological cancer alarm symptoms. Higher age, being immigrant and higher educational level increased the odds of GP contact. Future studies should explore the reasons for these findings as this may aid in prompting early diagnosis and thereby improve the prognosis of gynaecological cancer.

https://ift.tt/2KyC1rT

Accuracy of colorectal cancer ICD-9-CM codes in Italian administrative healthcare databases: a cross-sectional diagnostic study

Objectives To assess the accuracy of International Classification of Diseases, Ninth Revision – Clinical Modification (ICD-9-CM) codes in identifying subjects with colorectal cancer.

Design

A diagnostic accuracy study comparing ICD-9-CM codes (index test) for colorectal cancers with medical chart (as a reference standard). Case ascertainment based on neoplastic lesion(s) within the colon/rectum and histological documentation from a primary or metastatic site positive for colorectal cancer.

Setting

Administrative databases from the Umbria region, Azienda Sanitaria Locale (ASL) Napoli 3 Sud (NA) region and Friuli Venezia Giulia (FVG) region.

Participants

We randomly selected 130 incident patients from each hospital discharge database, admitted between 2012 and 2014, having colorectal cancer ICD-9 codes located in primary position, and 94 non-cases, that is, patients having a diagnosis of cancer (ICD-9 140–239) other than colorectal cancer in primary position.

Outcome measures

Sensitivity, specificity and predictive values for 153.x code (colon cancer) and for 154.x code (rectal cancer).

Results

The positive predictive value (PPV) for colon cancer diagnoses was 80% for Umbria (95% CI 73% to 87%), 81% for NA (95% CI 73% to 88%) and 80% for FVG (95% CI 72% to 87%).

The sensitivity ranged from 98% to 99%, while the specificity ranged from 78% to 80% in the three units.

For rectal cancer, the PPV was 84% for Umbria (95% CI 77% to 90%), 80% for NA (95% CI 72% to 87%) and 81% for FVG (95% CI 73% to 87%). The sensitivities ranged from 98% to 100%, while the specificity estimates from 79% to 82%.

Conclusions

Administrative databases in Italy can be a valuable tool for cancer surveillance as well as monitoring geographical and temporal variation of cancer practice.

https://ift.tt/2MRXDfy

Exploration and characterisation of the phenotypic and genetic profiles of patients with early onset schizophrenia associated with autism spectrum disorder and their first-degree relatives: a French multicentre case series study protocol (GenAuDiss)

Introduction

Early-onset schizophrenia (EOS) is a rare and severe condition. A higher rate of neurodevelopmental abnormalities, such as intellectual or communication impairments as well as attention deficit hyperactivity disorder, is observed in EOS compared with adult-onset schizophrenia. Early signs of autism spectrum disorders (ASD) are present in about 30% of patients. Genetic abnormalities, including copy number variations, are frequent in neurodevelopmental disorders and have been associated to ASD physiopathology. Implicated genes encode proteins involved in brain development, synapses morphology and plasticity and neurogenesis. In addition, an increasing number of genetic abnormalities are shared by EOS and ASD, underlying the neurodevelopmental hypothesis of EOS.

The main objective of our study is to identify disease-causing genetic mutations in a cohort of patients affected by both EOS and ASD. Special attention will be paid to genes involved in neurodevelopmental pathways.

Methods and analysis

We describe a multicentric study in a paediatric population. The study started in April 2014. Inclusion criteria are: age 7–22 years, diagnosis of EOS with comorbid ASD and IQ >50; Parents and siblings are also enrolled. We perform psychiatric assessments (Mini International Neuropsychiatric Interview, Kiddie Schedule for Affective Disorders and Schizophrenia -Present and Lifetime Version, Positive and Negative Syndrome Scale and Scale for the Assessment of Negative Symptoms) together with neurocognitive evaluations (IQ, Trail Making Test A/B and verbal fluency). Then, we study variants of the coding part of DNA (exome), using next-generation sequencing process on trio (mother, father and child). Bioinformatics tools (RVIS and PolyPhen-2) are used to prioritise disease-causing mutations in candidate genes. The inclusion period will end in November 2019.

Ethics and dissemination

The study protocol was approved by the Local Ethic Committee and by the French National Agency for Medicines and Health Products Safety. All patients signed informed consent on enrolment in the study. Results of the present study should help to unravel the molecular pathology of EOS, paving the way for an early therapeutic intervention.

Trial registration number

NCT0256552; Pre-results.

https://ift.tt/2KD2CUL

Nonionic surfactants and their effects on asymmetric reduction of 2-octanone with Saccharomyces cerevisiae

In an aqueous buffer system, serious reverse and side reactions were found in the asymmetric reduction of 2-octanone with Saccharomyces cerevisiae. However, some nonionic surfactants added to the aqueous buffer s...

https://ift.tt/2KMyghT

18 F-NaF and 18 F-FDG as molecular probes in the evaluation of atherosclerosis

Abstract

The early detection of atherosclerotic disease is vital to the effective prevention and management of life-threatening cardiovascular events such as myocardial infarctions and cerebrovascular accidents. Given the potential for positron emission tomography (PET) to visualize atherosclerosis earlier in the disease process than anatomic imaging modalities such as computed tomography (CT), this application of PET imaging has been the focus of intense scientific inquiry. Although ¹⁸F-FDG has historically been the most widely studied PET radiotracer in this domain, there is a growing body of evidence that ¹⁸F-NaF holds significant diagnostic and prognostic value as well. In this article, we review the existing literature on the application of ¹⁸F-FDG and ¹⁸F-NaF as PET probes in atherosclerosis and present the findings of original animal and human studies that have examined how well ¹⁸F-NaF uptake correlates with vascular calcification and cardiovascular risk.

https://ift.tt/2KxyQR8

IL-6 mediates cross-talk between activated fibroblasts and tumor cells in the tumor microenvironment

The tumor microenvironment (TME) plays a major role in the pathogenesis of multiple cancer types, including upper-gastrointestinal (GI) cancers that currently lack effective therapeutic options. Cancer-associated fibroblasts (CAF) are an essential component of the TME, contributing to tumorigenesis by secreting growth factors, modifying the extracellular matrix, supporting angiogenesis, and suppressing anti-tumor immune responses. Through an unbiased approach, we have established that IL-6 mediates crosstalk between tumor cells and CAF not only by supporting tumor cell growth, but also by promoting fibroblast activation. As a result, IL-6 receptor (IL-6Rα) and downstream effectors offer opportunities for targeted therapy in upper-GI cancers. IL-6 loss suppressed tumorigenesis in physiologically relevant 3D organotypic and 3D tumoroid models and murine models of esophageal cancer. Tocilizumab, an anti-IL-6Rα antibody, suppressed tumor growth in vivo in part via inhibition of STAT3 and MEK/ERK signaling. Analysis of a pan-cancer TCGA dataset revealed an inverse correlation between IL-6 and IL-6Rα overexpression and patient survival. Therefore, we expanded evaluation of tocilizumab to head-and-neck squamous cell carcinoma patient-derived xenografts and gastric adenocarcinoma xenografts, demonstrating suppression of tumor growth and altered STAT3 and ERK1/2 gene signatures. We used small molecule inhibitors of STAT3 and MEK1/2 signaling to suppress tumorigenesis in the 3D organotypic model of esophageal cancer. We demonstrate that IL-6 is a major contributor to the dynamic crosstalk between tumor cells and CAF in the TME. Our findings provide a translational rationale for inhibition of IL-6Rα and downstream signaling pathways as a novel targeted therapy in oral-upper-GI cancers.

https://ift.tt/2NoDYoF

Replication stress drives constitutive activation of the DNA damage response and radioresistance in glioblastoma stem-like cells

Glioblastoma (GBM) is a lethal primary brain tumor characterized by treatment resistance and inevitable tumor recurrence, both of which are driven by a subpopulation of GBM cancer stem-like cells (GSC) with tumorigenic and self-renewal properties. Despite having broad implications for understanding GSC phenotype, the determinants of upregulated DNA damage response (DDR) and subsequent radiation resistance in GSC are unknown and represent a significant barrier to developing effective GBM treatments. In this study, we show that constitutive DDR activation and radiation resistance are driven by high levels of DNA replication stress (RS). CD133+ GSC exhibited reduced DNA replication velocity and a higher frequency of stalled replication forks than CD133- non-GSC in vitro; immunofluorescence studies confirmed these observations in a panel of orthotopic xenografts and human GBM specimens. Exposure of non-GSC to low-level exogenous RS generated radiation resistance in vitro, confirming RS as a novel determinant of radiation resistance in tumor cells. GSC exhibited DNA double strand breaks (DSB) which co-localized with 'replication factories' and RNA: DNA hybrids. GSC also demonstrated increased expression of long neural genes (>1Mbp) containing common fragile sites, supporting the hypothesis that replication/transcription collisions are the likely cause of RS in GSC. Targeting RS by combined inhibition of ATR and PARP (CAiPi) provided GSC-specific cytotoxicity and complete abrogation of GSC radiation resistance in vitro. These data identify RS as a cancer stem cell-specific target with significant clinical potential.

https://ift.tt/2tU9yCz

WHO Calls for Renewed Effort to Combat Chronic Disease

THURSDAY, July 5, 2018 -- The World Health Organization (WHO) Independent High-Level Commission has proposed six recommendations to address the growing epidemic of non-communicable diseases (NCDs), according to a report published online June 1 in...

https://ift.tt/2tU57Yr

NIH Warns of Increased Risk of Heat-Related Illness for Seniors

THURSDAY, July 5, 2018 -- Older adults are at significantly increased risk of heat-related illnesses, which can include heat stroke, heat edema, heat syncope, heat cramps, and heat exhaustion, according to the National Institutes of Health. Factors...

https://ift.tt/2u9dTkn

Hospitals Face $218B in Federal Payment Cuts From 2010 to 2028

THURSDAY, July 5, 2018 -- Cumulative reductions in federal payments to hospitals from 2010 to 2028 are estimated to reach $218.2 billion, according to a study commissioned by the Federation of American Hospitals and the American Hospital Association...

https://ift.tt/2tYR2c0

Patisiran, Inotersen Aid Hereditary Transthyretin Amyloidosis

THURSDAY, July 5, 2018 -- For patients with hereditary transthyretin amyloidosis with polyneuropathy, an investigational RNA interference therapeutic agent (patisiran) and a 2'-O-methoxyethyl-modified antisense oligonucleotide (inotersen), which...

https://ift.tt/2zdJyab

Patient Complaints Mainly About Rudeness, Rushing, Reproach

THURSDAY, July 5, 2018 -- Understanding patients' complaints about practice can be instructive for physicians, according to an article published June 6 in Physicians Practice. Based on e-mails received in relation to a previous article, author Sue...

https://ift.tt/2tZ74CV

Targeting IgE in allergic disease

Pascal Gasser | Alexander Eggel

https://ift.tt/2KMRvba

Patella fractures are not associated with an increased risk of mortality in elderly patients

Publication date: Available online 5 July 2018

Source: Injury

Author(s): Peter Larsen, Rasmus Elsoe

ABSTRACT

Introduction

The modern literature includes only limited information regarding mortality rates and cumulative survival following patella fractures. The aim was to report the 30-day, six-month, and one-year mortality of patients with patella fractures and compare this to the mortality of a matched reference population.

Methods

All patients who sustained a patella fracture in Denmark between 1996 and 2000 were included in the study. The survival status of these patients was monitored until 2015. We compare the mortality with a ten-fold reference population matched on age and gender without a prior patella fracture.

Results

6096 patients were treated for 6114 patella fractures. The mean age of patients was 48.9 years. The overall mortality rates at 30 days, six months, and one year were 0.7%, 1.8%, and 2.8%. The mortality rates for patients > 65 years at 30 days, six months, and one year were 1.3%, 3.9%, and 6.2%. The mortality rates for patients at ≤ 65 years at 30 days, six months, and one year were 0.4%, 0.9%, and 1.3%. Compared to the matched reference population, the relative risk of mortality in patients > 65 years at 30 days, six months, and one year were 1.9 (95% CI 1.2-2.9), 1.0 (95% CI 0.8-1.3), and 0.9 (95% CI 0.7-1.1).

Conclusion

The overall one-year mortality rate of patella fractures was 2.8% and this was increased to 6.2% in patients older than 65 years. In elderly patients above 65 years, the relative risk of death was 0.9, indicating that patella fractures in elderly patients were not associated with an increased mortality rate.

https://ift.tt/2KP4LvC

Intra-operative fluoroscopy time and radiation dose during Suprapatellar tibial nailing versus Infrapatellar tibial nailing

Publication date: Available online 5 July 2018

Source: Injury

Author(s): M. Williamson, E. Iliopoulos, R. Williams, A. Trompeter

Abstract

Background

Fractures of the tibial shaft are routinely managed with intramedullary nailing. An increasingly accepted technique is the suprapatellar extended leg method. The aim of this study was to investigate whether the suprapatellar tibial nailing technique offers shorter intraoperative fluoroscopy times and lower radiation doses when compared to the traditional infrapatellar technique.

Study Design and Methods

Data from 200 consecutive intramedullary tibial nailing operations in our level 1 Major Trauma Centre were retrospectively collected from a prospective database (January 2014 - December 2017). Only acute diaphyseal nailing procedures were included. The operations were performed by seven senior trauma consultants experienced in both suprapatellar and infrapatellar tibial nailing. The operations were divided into two groups: infrapatellar and suprapatellar. Intraoperative radiation time and dose data were collected.

Results

A total of 90 cases were included and analysed. The majority of the patients were male (82%). 37 operations were infrapatellar and 53 were suprapatellar. Independent samples t test revealed lower radiation time and dose for the suprapatellar group. The infrapatellar group had a mean radiation time of 129.7 ± 56.6 seconds versus 94.4 ± 47.9 seconds for the suprapatellar group. The infrapatellar group had a mean radiation dose (Dose Area Product) 53.6 ± 34.2 cGY.cm² versus 38.2 ± 26.7 cGY.cm² for the suprapatellar group. The difference in mean radiation time and mean radiation dose were both significant (p = 0.002 and p = 0.02 respectively).

Conclusions

Suprapatellar tibial nailing is an increasingly accepted technique in the management of tibial fractures. It is shown here that amongst surgeons experienced in both suprapatellar and infrapatellar nailing techniques, the suprapatellar approach trends towards lower use of intra-operative fluoroscopy as measured by time and dose and thus potentially lower radiation exposure to the operating surgeon, assistants and patient.

https://ift.tt/2KRbAtv

Pain after ortho-plastic reconstruction of lower limb injuries: The importance of standardizing analgesic management

Publication date: June 2018

Source: Injury, Volume 49, Issue 6

Author(s): Mark C. Kendall, Lucas J. Castro Alves

https://ift.tt/2KBIgev

Tetanus ‘Quick Stik’ – is the NHS missing a trick?

Publication date: June 2018

Source: Injury, Volume 49, Issue 6

Author(s): T. Welman, A.R. McKean, E. Duggan, S.M. Rahman, L.S.P. Moore, M. Horwitz

https://ift.tt/2KOf5AZ

Severe Vitamin D3 Deficiency in the Majority of Patients with Diabetic Foot Ulcers

Horm Metab Res
DOI: 10.1055/a-0648-8178

Diabetic foot ulcers are a severe complication in patients with diabetes mellitus. Vitamin D is associated with impaired β-cell function and insulin resistance, and is necessary for wound healing and bone metabolism. We measured the serum concentrations of 25-hydroxyvitamin D3 in 104 patients (63 inpatients, 41 outpatients) with diabetic foot ulcers and compared them to 99 healthy humans (control) and 103 patients with diabetes mellitus type 2 without diabetic foot ulcers. Calcium, creatinine, and parathyroid hormone were measured in patients with diabetic foot ulcers. The data were analysed together with glycosylated hemoglobin A1c and the severity of diabetic foot lesions according to the Armstrong classification. Levels of 25-hydroxyvitamin D3 were lower (11.8±11.3 ng/ml, p<0.001) in patients with diabetic foot ulcers (mean age 70±12 years) than in the control group (27.2±12.2 ng/ml). No difference was found between in- and outpatients. Fifty-eight (55.8%) of patients with diabetic foot ulcers had a severe 25-hydroxyvitamin D3 deficiency with levels below 10 ng/ml. Only 12% of the patients had 25-hydroxyvitamin D3 levels above 20 ng/ml. Secondary hyperparathyroidism was found in 27.9% of patients and 11.5% of the patients were hypocalcemic. There was a negative correlation (r=–0.241) (p<00.1) between Armstrong classification and 25-hydroxyvitamin D3 status. In conclusion, patients with diabetic foot syndrome are at high risk of 25-hydroxyvitamin D3 deficiency. Thus, any patient with diabetic foot syndrome should undergo 25-hydroxyvitamin D3 measurement and supplementation, if values are found to be decreased.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

https://ift.tt/2KyclM1

Use of Enteral Nutrition for Gastrointestinal Bleeding Prophylaxis in the Critically Ill: Review of Current Literature

Abstract

Purpose of Review

This review provides a comprehensive overview of the etiology of stress-related mucosal disease, current acid suppression therapy recommendations, and the role enteral nutrition may play in disease prevention.

Recent Findings

Recent literature indicates enteral nutrition may prevent complications of stress-related mucosal disease by increasing splanchnic blood flow, enhancing gastrointestinal motility, and promoting cellular immunity and integrity through local nutrient delivery.

Summary

Stress-related mucosal disease is a common complication of hospitalization in the critically ill which may lead to overt gastrointestinal bleeding and enhanced mortality. High-risk patients have historically been prescribed acid suppression therapy, though enteral nutrition may also have a role in disease mitigation.

https://ift.tt/2KR89D6

The Role of Nutrition in Cognitive Function and Brain Ageing in the Elderly

Abstract

Purpose of Review

The purposes of this review were to examine literature published over the last 5 years and to evaluate the role of nutrition in cognitive function and brain ageing, focussing on the Mediterranean diet (MeDi), Dietary Approaches to Stop Hypertension (DASH), and Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diets.

Recent Findings

Results suggest that higher adherence to a healthy dietary pattern is associated with preservation of brain structure and function as well as slower cognitive decline, with the MIND diet substantially slowing cognitive decline, over and above the MeDi and DASH diets.

Summary

Whilst results to-date suggest adherence to a healthy diet, such as the MeDi, DASH, or MIND, is an important modifiable risk factor in the quest to develop strategies aimed at increasing likelihood of healthy brain ageing, further work is required to develop dietary guidelines with the greatest potential benefit for public health; a research topic of increasing importance as the world's population ages.

https://ift.tt/2MSGl1W

Human Papillomavirus Seroprevalence and Association with Anal HPV Infection and Squamous Intraepithelial Lesions in Australian Gay and Bisexual Men

Background: Gay and bisexual men (GBM) are at disproportionately high risk of anal cancer. The precursor lesions, high-grade squamous intraepithelial lesions (HSIL), are very common and it is evident that not all HSIL progresses to cancer. The serologic response to anal human papillomavirus (HPV) in GBM has not been well characterized.

Methods: The Study of the Prevention of Anal Cancer is an ongoing cohort study of GBM ages 35 years and older. At six visits over three years, anal samples are collected for cytology, HPV DNA testing, and histology. Baseline serum was tested for HPV L1, E6, and E7 antibodies for 10 HPV types. Seroprevalence and associated predictors were analyzed.

Results: A total of 588 of 617 participants were included in this analysis. A total of 436 (74.2%) were seropositive for at least one of the 10 HPV types. Almost half had L1 antibodies to HPV6 (48.5%), over a third to HPV11 (36.4%) and HPV16 (34.5%). HIV-positive men were more likely to be HPV L1 seropositive. HSIL detection was highest among participants who were HPV serology and DNA positive. There was a borderline significant association between presence of HPV16 E6 antibodies and prevalent HSIL (OR = 2.97; 95% confidence interval, 0.92–9.60; P = 0.068).

Conclusions: HPV L1 seropositivity was common in this cohort of older GBM. These results suggest that HPV L1 seropositivity, in conjunction with anal HPV DNA detection, predicts concurrent HSIL. The apparent association between HPV16 E6 antibodies and prevalent HSIL is a finding with potential clinical significance that needs further exploration.

Impact: HPV seropositivity with concurrent DNA detection predicted anal HSIL detection. Cancer Epidemiol Biomarkers Prev; 27(7); 768–75. ©2018 AACR.

https://ift.tt/2zl4See

Fat Intake and Risk of Skin Cancer in U.S. Adults

Background: Fat intake has been associated with certain cancers, including colorectal, breast, and prostate cancers. However, literature on dietary fat and skin cancer has been limited.

Methods: We examined the association between fat intake and risk of skin cancer including cutaneous malignant melanoma, squamous cell carcinoma (SCC), and basal cell carcinoma (BCC) within two prospective studies: the Nurses' Health Study (NHS) and the Health Professionals Follow-up Study (HPFS). Dietary information on total, saturated, monounsaturated, polyunsaturated, omega-6, and omega-3 fat and cholesterol was repeatedly assessed generally every 4 years. Incident cases were identified by self-report. Diagnosis on melanoma and SCC was confirmed by pathologic records.

Results: A total of 794 melanoma, 2,223 SCC, and 17,556 BCC in the NHS (1984–2012) and 736 melanoma, 1,756 SCC, and 13,092 BCC in the HPFS (1986–2012) were documented. Higher polyunsaturated fat intake was associated with risk of SCC [pooled HR for highest vs. lowest quintiles, 1.16; 95% confidence interval (CI), 1.05–1.28; P_trend=0.001] and BCC (pooled HR, 1.06; 95% CI, 1.01–1.11; P_trend=0.01). Higher omega-6 fat intake was associated with risks of SCC, BCC, and melanoma. Omega-3 fat intake was associated with risk of BCC, but not with SCC or melanoma. No other fats were associated with melanoma risk. The associations were similar in women and men and by other skin cancer risk factors.

Conclusions: Polyunsaturated fat intake was modestly associated with skin cancer risk.

Impact: Further studies are needed to confirm our findings and to identify relevant biological mechanisms. Cancer Epidemiol Biomarkers Prev; 27(7); 776–82. ©2018 AACR.

https://ift.tt/2lXWac2

Telomere Length and Lung Cancer Mortality among Heavy Smokers

Background: Accumulating evidence suggests that short telomere length is associated with increased overall mortality, but the relationship with cancer mortality is less clear. We examined whether telomere length (global, and chromosome arm 5p- and 13q-specific) is associated with lung cancer mortality among cases from the β-Carotene and Retinol Efficacy Trial of heavy smokers.

Methods: Telomere length was measured on average 6 years before diagnosis for 788 lung cancer cases. Adjusted Cox proportional hazards models of all-cause and lung cancer–specific mortality were assessed for lung cancer overall and by histotype.

Results: Short telomere length was associated with increased mortality for small cell lung cancer (SCLC), particularly stage III/IV SCLC [HR and 95% confidence interval for shortest vs. longest telomere length tertile: 3.32 (1.78–6.21)]. Associations were strongest for those randomized to the active intervention and when telomere length was measured ≤5 years before diagnosis. All-cause mortality patterns were similar. Short chromosome 5p telomere length was suggestively associated with lung cancer mortality, but there was no association with chromosome 13q telomere length.

Conclusions: Our large prospective study suggests that among heavy smokers who developed lung cancer, short prediagnosis telomere length is associated with increased risk of death from SCLC.

Impact: This is the first study to examine telomere length and mortality in lung cancer cases by histotype. If the association between short telomere length and SCLC mortality is replicated, elucidation of mechanisms through which telomere length influences survival for this highly aggressive cancer may inform more effective use of telomere-targeted therapeutics. Cancer Epidemiol Biomarkers Prev; 27(7); 829–37. ©2018 AACR.

https://ift.tt/2u7RAMc

A Genetic Variant Located in miR-146b Promoter Region Is Associated with Prognosis of Gastric Cancer

Background: SNPs in the promoter region of miRNAs have been reported to be associated with cancer prognosis. Our previous study found that miR-146b had a strong correlation with the stage classification of gastric cancer and contributed to tumor progression. The current study was aimed at investigating whether an SNP located in the promoter region of miR-146b could affect the survival rate of gastric cancer.

Methods: Using bioinformatics tools, we identified one SNP (rs1536309) that is located in the miR-146b promoter. We genotyped this SNP site to assess its association with gastric cancer prognosis in 940 cases.

Results: We found that the dominant model of miR-146b rs1536309 was associated with a higher survival rate of gastric cancer. The association remained significant in the subgroup analysis by age (≤60), sex (male), tumor size (≤5 cm), histologic type (diffuse), lymph node metastasis (N0), distant metastasis (M0), and TNM stage (I/II).

Conclusions: Our results suggested that the miR-146b rs1536309 polymorphism may be a potential biomarker for the prognosis of gastric cancer.

Impact: This is the first evidence showing that patients carrying the miR-146b-5p rs1536309 CC/CT genotypes exhibited better survival than those carrying the TT genotype, suggesting the protective effect of the C allele in the prognosis of gastric cancer. Cancer Epidemiol Biomarkers Prev; 27(7); 822–8. ©2018 AACR.

https://ift.tt/2lXW5oK

Common Mitochondrial Haplogroups and Cutaneous Squamous Cell Carcinoma Risk

Background: Cutaneous squamous cell carcinoma (cSCC) is the second most common cancer in United States, and its incidence is substantially higher in men than women, but the reasons for the difference are unknown. We explored whether common mitochondrial DNA (mtDNA) haplogroups, which have been associated with cancer risk, and in particular squamous cell carcinoma risk arising in other organs, could explain this biological sex difference in cSCC susceptibility.

Methods: We performed a retrospective cohort study using data from the Genetic Epidemiology Research in Adult Health and Aging cohort composed of 67,868 non-Hispanic white subjects (7,701 cSCC cases and 60,167 controls). Genotype information on >665,000 SNPs was generated using Affymetrix Axiom arrays designed to maximize genome-wide coverage, and 102 high-quality mtDNA SNPs were used to determine mtDNA haplogroups. Associations between each mtDNA haplogroup and cSCC risk were evaluated by logistic regression analysis adjusting for age, sex, and population stratification using ancestry principal components.

Results: cSCC was more common in men (15.4% vs. 8.4% for women). Nine common mtDNA haplogroups (frequency ≥1%) were identified in addition to the most common haplogroup, H, used as the reference group. No association with cSCC risk was detected for any of the mtDNA haplogroups or overall or sex-stratified analyses.

Conclusions: Common mitochondrial variation is not associated with cSCC risk.

Impact: This well-powered study refutes the hypothesis that common mitochondrial haplogroups play a role in the differential sex predilection of cSCCs. Cancer Epidemiol Biomarkers Prev; 27(7); 838–41. ©2018 AACR.

https://ift.tt/2u7RxA0

Association of Coffee and Tea Intake with the Oral Microbiome: Results from a Large Cross-Sectional Study

Background: The oral microbiota play a central role in oral health, and possibly in carcinogenesis. Research suggests that coffee and tea consumption may have beneficial health effects. We examined the associations of these common beverages with the oral ecosystem in a large cross-sectional study.

Methods: We assessed oral microbiota in mouthwash samples from 938 participants in two U.S. cohorts using 16S rRNA gene sequencing. Coffee and tea intake were assessed from food frequency questionnaires. We examined associations of coffee and tea intake with overall oral microbiota diversity and composition using linear regression and permutational MANOVA, respectively, and with taxon abundance using negative binomial generalized linear models; all models adjusted for age, sex, cohort, body mass index, smoking, ethanol intake, and energy intake.

Results: Higher tea intake was associated with greater oral microbiota richness (P = 0.05) and diversity (P = 0.006), and shifts in overall community composition (P = 0.002); coffee was not associated with these microbiome parameters. Tea intake was associated with altered abundance of several oral taxa; these included Fusobacteriales, Clostridiales, and Shuttleworthia satelles (higher with increasing tea) and Bifidobacteriaceae, Bergeyella, Lactobacillales, and Kingella oralis (lower with increasing tea). Higher coffee intake was only associated with greater abundance of Granulicatella and Synergistetes.

Conclusions: In the largest study to date of tea and coffee consumption in relation to the oral microbiota, the microbiota of tea drinkers differed in several ways from nondrinkers.

Impact: Tea-driven changes to the oral microbiome may contribute to previously observed associations between tea and oral and systemic diseases, including cancers. Cancer Epidemiol Biomarkers Prev; 27(7); 814–21. ©2018 AACR.

https://ift.tt/2lXCxB7

Parents' Views on the Best and Worst Reasons for Guideline-Consistent HPV Vaccination

Background: Human papillomavirus (HPV) vaccination could prevent most HPV-associated cancers, but few U.S. adolescents are vaccinated according to guidelines. To inform efforts to counsel parents more effectively, we sought to quantify their views on the best and worst reasons for guideline-consistent HPV vaccination. We hypothesized that parents' views would differ according to their vaccination confidence.

Methods: We developed a best–worst scaling experiment to evaluate 11 reasons healthcare providers commonly give for HPV vaccination. The instrument was administered in 2016 via a national online survey to 1,177 parents of adolescents. Parents completed 11 choice tasks of 5 reasons each, indicating the best and worst reason in each task. We used conditional logistic regression to rank reasons for the sample overall and by vaccination confidence (low/high).

Results: Parents viewed cancer prevention as the best reason for HPV vaccination (P < 0.001). Other commonly endorsed reasons were preventing a common infection, having lasting benefits, or being a safe vaccine (all P < 0.001). Reasons viewed as worst were: It is a scientific breakthrough; I got it for my own child; and your child is due (all P < 0.001). Stratified analyses indicated small differences in how often parents with low versus high vaccination confidence endorsed messages (P < 0.001), but the two groups ranked reasons similarly overall.

Conclusions: Parents prioritized cancer prevention as the best reason for guideline-consistent HPV vaccination. Several other common reasons, including having vaccinated one's own child, may warrant additional testing.

Impact: Providers should emphasize cancer prevention when discussing HPV vaccination, as recommended by the Centers for Disease Control and Prevention, the President's Cancer Panel, and others. Cancer Epidemiol Biomarkers Prev; 27(7); 762–7. ©2018 AACR.

https://ift.tt/2zgq7xI

Anti-CA15.3 and Anti-CA125 Antibodies and Ovarian Cancer Risk: Results from the EPIC Cohort

Background: Neoplastic and non-neoplastic events may raise levels of mucins, CA15.3, and CA125, and generate antibodies against them, but their impact on epithelial ovarian cancer (EOC) risk has not been fully defined.

Methods: CA15.3, CA125, and IgG1 antibodies against them were measured in 806 women who developed EOC and 1,927 matched controls from the European Prospective Investigation of Nutrition and Cancer. Associations between epidemiologic factors and anti-mucin antibodies were evaluated using generalized linear models; EOC risks associated with anti-mucin antibodies, by themselves or in combination with respective antigens, were evaluated using conditional logistic regression.

Results: In controls, lower antibodies against both mucins were associated with current smoking; and, in postmenopausal women, higher levels with longer oral contraceptive use and later-age-at and shorter-interval-since last birth. Lower anti-CA15.3 antibodies were associated with higher body mass and, in premenopausal women, more ovulatory cycles. Higher anti-CA15.3 and anti-CA125 antibodies were associated with higher risk for mucinous EOC occurring ≥ 3 years from enrollment. Long-term risk for serous EOC was reduced in women with low CA125 and high anti-CA125 antibodies relative to women with low concentrations of both.

Conclusions: We found general support for the hypothesis that anti-mucin antibody levels correlate with risk factors for EOC. Antibodies alone or in combinations with their antigen may predict longer term risk of specific EOC types.

Impact: Anti-CA125 and anti-CA15.3 antibodies alone or in perspective of antigens may be informative in the pathogenesis of EOC subtypes, but less useful for informing risk for all EOC. Cancer Epidemiol Biomarkers Prev; 27(7); 790–804. ©2018 AACR.

https://ift.tt/2lXW04q

Immunohistochemical Expression of Cortactin and Focal Adhesion Kinase Predicts Recurrence Risk and Laryngeal Cancer Risk Beyond Histologic Grading

Background: Cortactin (CTTN) and the focal adhesion kinase (FAK) are two major candidate genes to, respectively, drive 11q13- and 8q24-associated aggressive behavior in various cancers. Recent evidence uncovered their clinical relevance in early stages of tumorigenesis as promising biomarkers for cancer risk assessment.

Methods: Using a multicenter validation study, CTTN and FAK expression was evaluated by immunohistochemistry (IHC) in a cohort of 109 patients with laryngeal precancerous lesions, and correlated with clinicopathologic parameters and laryngeal cancer risk. The pathophysiologic role of CTTN and FAK was further investigated using functional studies in cellular models.

Results: Positive CTTN and FAK expression (scores 2 and 3) was detected in 49 (41%) and 35 (32%) laryngeal dysplasias, respectively. Univariate Cox analysis showed that CTTN and FAK expression but not histologic grading was significantly associated with both recurrence risk and laryngeal cancer risk. Patients carrying strong CTTN- or FAK-expressing lesions (score 3) experienced the highest laryngeal cancer incidence (log-rank P < 0.001). In multivariate stepwise analysis, FAK expression [HR = 13.91; 95% CI, 4.82–40.15; P < 0.001] and alcohol consumption (HR = 2.22; 95% confidence interval, 1.17–4.20; P = 0.014) were significant independent predictors of laryngeal cancer development. Targeting FAK by either RNAi or pharmacologic inhibitors effectively blocked cell growth, colony formation, and invasion into 3D collagen matrices.

Conclusions: CTTN and FAK emerge as powerful predictors of laryngeal cancer risk and recurrence risk beyond histologic grading.

Impact: Our work supports the applicability of IHC CTTN and FAK as complementary markers for risk stratification in patients with laryngeal precancerous lesions. Cancer Epidemiol Biomarkers Prev; 27(7); 805–13. ©2018 AACR.

https://ift.tt/2u7LWtj

Geographic Differences in Baseline Prostate Inflammation and Relationship with Subsequent Prostate Cancer Risk: Results from the Multinational REDUCE Trial

Background: Prostate cancer incidence rates vary 25-fold worldwide. Differences in PSA screening are largely, but not entirely, responsible. We examined geographic differences in prevalence of histologic prostate inflammation and subsequent prostate cancer risk.

Methods: Seven thousand nonHispanic white men were enrolled in the REduction by DUtasteride of prostate Cancer Events (REDUCE) trial from Europe (n = 4,644), North America (n = 1,746), South America (n = 466), and Australia/New Zealand (n = 144). Histologic inflammation in baseline negative prostate biopsies was classified as chronic (lymphocytes/macrophages) or acute (neutrophils). Multivariable logistic regression was used to examine associations between region and prostate inflammation, and between region and prostate cancer risk at 2-year biopsy.

Results: Prevalence of prostate inflammation varied across region, with broadly similar patterns for acute and chronic inflammation. Relative to Europe, prevalence of acute inflammation was higher in North America [odds ratio (OR), 1.77; 95% confidence interval (CI), 1.51–2.08] and Australia/New Zealand (OR, 2.07; 95% CI, 1.40–3.06). Men from these regions had lower prostate cancer risk than Europeans at biopsy. Among North Americans, prevalence of acute inflammation was higher in Canada versus the United States (OR, 1.40; 95% CI, 1.07–1.83), but prostate cancer risk did not differ between these regions. Among Europeans, prevalence of acute inflammation was lower in Northern and Eastern (OR, 0.79; 95% CI, 0.65–0.97 and OR 0.62; 95% CI, 0.45–0.87, respectively), relative to Western Europe, and these men had higher prostate cancer risk at biopsy.

Conclusions: Prevalence of histologic prostate inflammation varied by region. Geographic differences in prostate inflammation tracked inversely with geographic differences in prostate cancer risk.

Impact: Characterization of premalignant prostate biology and the relationship with subsequent prostate cancer risk could inform prostate cancer prevention efforts. Cancer Epidemiol Biomarkers Prev; 27(7); 783–9. ©2018 AACR.

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Association between Nonsteroidal Anti-Inflammatory Drugs and Colorectal Cancer: A Population-Based Case-Control Study

Background: COX-2 overexpression may contribute to colorectal cancer occurrence. Aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) can reduce colorectal cancer recurrence, but the efficacy of primary prevention in Asian populations is still elusive. Thus, we examined the primary preventive efficacy of aspirin and NSAIDs on colorectal cancer incidence in Taiwan.

Methods: A nested case–control study was conducted using the National Health Insurance Research Database (NHIRD) in Taiwan. We identified patients with diagnosis of colorectal cancer from 2005 to 2013 in the Registry of Catastrophic Illness Patient Database. We selected patients without colorectal cancer from the Longitudinal Health Insurance Database as the controls and matched them with cases. NSAID exposure was defined as at least two prescriptions 13 to 48 months prior to the index date. Conditional logistic regression models were performed to evaluate the association between NSAID use and colorectal cancer.

Results: A total of 65,208 colorectal cancer cases and 65,208 matched controls were identified. Patients with aspirin use had a lower risk of colorectal cancer compared with nonusers [adjusted OR (AOR) = 0.94, 95% confidence interval (CI) = 0.90–0.99]. NSAID use was associated with lower incidence of colorectal cancer (AOR = 0.96; 95% CI = 0.92–1.00). When examining colon or rectal cancer, similar decreased risks were observed. Patients taking more cumulative days of NSAIDs use tended to experience a more protective effect on colorectal cancer, but no dose–response effects were noted.

Conclusions: Aspirin and NSAIDs were associated with a reduced risk of colorectal cancer development among a study cohort in an Asian population.

Impact: This study provided a possible chemoprevention for colorectal cancer in an Asian population. Cancer Epidemiol Biomarkers Prev; 27(7); 737–45. ©2018 AACR.

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Tumor-Infiltrating Lymphocytes and Colorectal Cancer Survival in African American and Caucasian Patients

Background: Compared with Caucasian Americans (CAs), African Americans (AAs) with colorectal cancer have poorer survival, especially younger-age patients. A robust lymphocytic reaction within colorectal cancers is strongly associated with better survival, but whether immune response impacts the disparity in colorectal cancer survival is unknown.

Methods: The study population was comprised of 211 histologically confirmed colorectal cancers at the Medical University of South Carolina (Charleston, SC; 159 CAs and 52 AAs) diagnosed between Jan 01, 2000, and June 30, 2013. We constructed a lymphocyte score based on blinded pathologic assessment of the four different types of lymphocytic reactions. Cox proportional hazards regression was used to evaluate the association between the lymphocyte score and risk of death by race.

Results: Colorectal cancers in AAs (vs. CAs) had a stronger lymphocytic reaction at diagnosis. A high lymphocyte score (vs. the lowest) was associated with better survival in AAs [HR 0.19; 95% confidence interval (CI), 0.04–0.99] and CAs (HR 0.47; 95% CI, 0.15–1.45). AAs with no lymphocytic reaction (vs. other categories) had poor survival HR 4.48 (1.58–12.7) whereas no difference was observed in CAs. The risk of death in AAs (vs. CA) was more pronounced in younger patients (HR 2.92; 95% CI, 1.18–7.22) compared with older (HR 1.20; 95% CI, 0.54–2.67), especially those with lymphocytic poor colorectal cancers.

Conclusions: The lymphocytic reaction in tumor impacted the racial disparity in survival.

Impact: Our results confirm the importance of the lymphocytic score on survival and highlight the need to fully characterize the immune environment of colorectal cancers by race. Cancer Epidemiol Biomarkers Prev; 27(7); 755–61. ©2018 AACR.

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Circulating Exosomal miR-27a and miR-130a Act as Novel Diagnostic and Prognostic Biomarkers of Colorectal Cancer

Background: Colorectal cancer is one of the most common cancers worldwide usually is associated with poor prognosis due to the advanced stage when diagnosed. This study aimed to investigate whether specific circulating exosomal miRNAs could act as biomarkers for early diagnosis of colorectal cancer.

Methods: A total of 369 peripheral blood samples were included in this study. In the discovery phase, circulating exosomal miR-27a and miR-130a were selected after synthetical analysis of two GEO datasets and TCGA database. The differential expression and diagnostic utility of miR-27a and miR-130a panel were validated using qRT-PCR and ROC curve analysis in subsequent training phase, validation phase, and external validation phase. The prognosis of circulating exosomal miR-27a and miR-130a were investigated using the Kaplan–Meier method.

Results: The expression of exosomal miR-27a and miR-130a in plasma significantly increased in colorectal cancer. The area under ROC curves (AUC) of miR-27a (miR-130a) were 0.773 (0.742) in the training phase, 0.82 (0.787) in the validation phase, and 0.746 (0.697) in the external validation phase. The combination of two miRNAs presented higher diagnostic utility for colorectal cancer (AUCs = 0.846, 0.898, and 0.801 for the training, validation, and external validation phases, respectively). Patients with colorectal cancer with high expression of circulating exosomal miR-27a or miR-130a underwent poorer prognosis.

Conclusions: We identified a circulating exosomal miRNAs panel for the detection of colorectal cancer.

Impact: The exosomal miR-27a and miR-130a panel in plasma may act as a noninvasive biomarker for early detection and predicting prognosis of colorectal cancer. Cancer Epidemiol Biomarkers Prev; 27(7); 746–54. ©2018 AACR.

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Highlights of This Issue

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Chemopreventive Efficacy of the Cyclooxygenase-2 (Cox-2) Inhibitor, Celecoxib, Is Predicted by Adenoma Expression of Cox-2 and 15-PGDH

Background: The Adenoma Prevention with Celecoxib (APC) Trial showed that cyclooxygenase-2 (Cox-2) inhibitor, celecoxib, decreased adenoma development in patients at high risk for colorectal cancer. A prospectively planned analysis of the APC Trial tested the hypothesis that expression of target enzymes in adenomas removed before beginning study treatment would identify individuals at high risk of adenoma development, and/or predict response to Cox-2 inhibition.

Methods: Pre-treatment adenomas were examined using immunohistochemistry to assess expression of Cox-2 (high vs. low) and 15-prostaglandin dehydrogenase (15-PGDH, presence vs. loss). The Mantel–Cox test evaluated whether these markers predicted benefit from celecoxib for reduction of adenoma detection.

Results: Patients whose pre-treatment adenomas demonstrated elevated Cox-2 achieved the greatest adenoma reduction with celecoxib treatment [RR, 0.37; 95% confidence interval (CI), 0.22–0.61; P = 0.0001]. This reduction was less in the low Cox-2 category (RR, 0.64; 95% CI, 0.56–0.73). Patients whose pre-treatment adenomas showed 15-PGDH loss had a similar treatment-associated reduction in adenoma detection (RR, 0.60; 95% CI, 0.52–0.69; P < 0.0001). In contrast, patients with intact tumor 15-PGDH expression did not significantly benefit from celecoxib (RR, 0.73; 95% CI, 0.47–1.12; P = 0.15). However, subset analysis suggested that this lack of response to celecoxib was confined to those patients with 15-PGDH intact tumors who were also using cardioprotective aspirin.

Conclusions: The expression of Cox-2 and 15-PGDH in pre-treatment adenomas provides predictive information in patients treated with celecoxib for prevention of colorectal adenomas.

Impact: The results of this study show that Cox-2 and 15-PGDH are characteristics of colorectal adenomas that may be used to predict nonsteroidal anti-inflammatory drug chemoprevention efficacy. Cancer Epidemiol Biomarkers Prev; 27(7); 728–36. ©2018 AACR.

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Circadian Misalignment and Hepatocellular Carcinoma Incidence in the United States

Background: Circadian misalignment may increase the risk of developing hepatocellular carcinoma (HCC). The aim of this study was to examine the association between distance from time zone meridian, a proxy for circadian misalignment, and HCC risk in the United States adjusting for known HCC risk factors.

Methods: Surveillance, Epidemiology, and End Results (SEER) provided information on 56,347 HCC cases diagnosed between 2000 and 2014 from 16 population-based cancer registries in the United States. Distance from time zone meridian was estimated using the location of each SEER county's Center of Population in a geographic information system. Poisson regression with robust variance estimation was used to calculate incidence rate ratios (IRRs) and 95% confidence intervals (CIs) for the association between distance from time zone meridian and HCC risk adjusting for individual-level age at diagnosis, sex, race/ethnicity, year of diagnosis, SEER registry, and county-level prevalence of health conditions, lifestyle factors, shift work occupation, socioeconomic status, and demographic and environmental factors.

Results: A 5-degree increase in longitude moving east to west within a time zone was associated with a statistically significant increased risk for HCC (IRR, 1.07; 95% CI, 1.01–1.14, P = 0.03). A statistically significant positive association was observed among those <65 years old, while no association was observed among individuals ≥65 years old (P_{for interaction} < 0.01).

Conclusions: Circadian misalignment from residing in the western region of a time zone may impact hepatocarcinogenesis.

Impact: Circadian misalignment may be an independent risk factor for HCC. Cancer Epidemiol Biomarkers Prev; 27(7); 719–27. ©2018 AACR.

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Impact of a structured yoga program on blood pressure reduction among hypertensive patients: study protocol for a pragmatic randomized multicenter trial in primary health care settings in Nepal

Hypertension control remains a major global challenge. The behavioral approaches recommended for blood pressure reduction are stress reduction, increased exercise and healthy dietary habits. Some study finding...

https://ift.tt/2NtBUM7

Phenolic profile, anti-inflammatory, antinociceptive, anti-ulcerogenic and hepatoprotective activities of Pimenta racemosa leaves

Pimenta racemosa tree has many traditional uses where its leaves are used as herbal tea for treatment of flatulence, gastric disorder, osteoarthritis, colds and fever in addition to its analgesic and anti-inflamm...

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High-Throughput Screening Identifies Kinase Inhibitors That Increase Dual Adeno-Associated Viral Vector Transduction In Vitro and in Mouse Retina

Human Gene Therapy, Ahead of Print.


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Water exchange colonoscopy increases adenoma detection rate: a systematic review with network meta-analysis of randomized controlled studies

Water-aided colonoscopy techniques (water immersion, WI; water exchange, WE) have shown different results regarding adenoma detection rate (ADR). We determined the impact of WI and WE on ADR and other procedural outcomes versus gas (air, AI; carbon dioxide, CO2) insufflation colonoscopy.

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Diagnostic criterion of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP): absence of papillae

Pedro Weslley Rosario MD pedrowsrosario@gmail.com

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Telocytes as possible precursors of PDGFRA-mutant gastrointestinal mesenchymal tumors

(See Fig..)

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Telocytes as possible precursors of PDGFRA-mutant gastrointestinal mesenchymal tumors—reply

We are pleased that Ricci et al. have provided supporting evidence for our hypothesis that the telocyte, the only CD34- and PDGFRA-positive cell of the stomach and intestines [1], is the cell of origin of inflammatory fibroid polyps (IFPs). IFPs arising sporadically or syndromically predominantly have a gain-of-function mutation within the PDGFRA gene and are CD34 and PDGFRA positive.

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https://ift.tt/2lXsJah

Anti-ADAM17 monoclonal antibody MEDI3622 increases IFNγ production by human NK cells in the presence of antibody-bound tumor cells

Abstract

Several clinically successful tumor-targeting mAbs induce NK cell effector functions. Human NK cells exclusively recognize tumor-bound IgG by the FcR CD16A (FcγRIIIA). Unlike other NK cell activating receptors, the cell surface density of CD16A can be rapidly downregulated in a cis manner by the metalloproteinase ADAM17 following NK cell stimulation in various manners. CD16A downregulation takes place in cancer patients and this may affect the efficacy of tumor-targeting mAbs. We examined the effects of MEDI3622, a human mAb and potent ADAM17 inhibitor, on NK cell activation by antibody-bound tumor cells. MEDI3622 effectively blocked ADAM17 function in NK cells and caused a marked increase in their production of IFNγ. This was observed for NK cells exposed to different tumor cell lines and therapeutic antibodies, and over a range of effector/target ratios. The augmented release of IFNγ by NK cells was reversed by a function-blocking CD16A mAb. In addition, NK92 cells, a human NK cell line that lacks endogenous FcγRs, expressing a recombinant non-cleavable version of CD16A released significantly higher levels of IFNγ than NK92 cells expressing equivalent levels of wildtype CD16A. Taken together, our data show that MEDI3622 enhances the release of IFNγ by NK cells engaging antibody-bound tumor cells by blocking the shedding of CD16A. These findings support ADAM17 as a dynamic inhibitory checkpoint of the potent activating receptor CD16A, which can be targeted by MEDI3622 to potentially increase the efficacy of anti-tumor therapeutic antibodies.

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Endometrial tuberculosis among patients undergoing endometrial biopsy at Tikur Anbesa specialized hospital, Addis Ababa, Ethiopia

Female genital tuberculosis (FGTB) is known to cause severe tubal disease leading to infertility and its incidence closely parallels with the overall prevalence of tuberculosis (TB) in a community. Its magnitu...

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Comparison of qPCR and culture methods for group B Streptococcus colonization detection in pregnant women: evaluation of a new qPCR assay

Streptococcus Group B (GBS) colonization in pregnant women is the most important risk factor for newborn disease due to vertical transmission during delivery. GBS colonization during pregnancy has been implicated...

https://ift.tt/2zkEcKC

Medical treatment of cystic echinococcosis: systematic review and meta-analysis

Cystic echinococcosis (CE) is a well-known neglected parasitic disease. However, evidence supporting the four current treatment modalities is inadequate, and treatment options remain controversial. The aim of ...

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The relation of secondary sex ratio and miscarriage history with Toxoplasma gondii infection

Toxoplasma gondii is a protozoan parasite with worldwide distribution, infecting a broad-range of humans and warm-blooded animals. In the current study, role of this parasite on secondary sex ratio and risk of mi...

https://ift.tt/2zfXWPs

High Patient Burden With Moderate-to-Severe Atopic Dermatitis

THURSDAY, July 5, 2018 -- Patients with moderate/severe atopic dermatitis (AD) have higher patient-reported burden than those with mild AD, regardless of disease control, according to a study published online July 3 in JAMA Dermatology. Eric L....

https://ift.tt/2lXrs31

Increase in Prevalence of Peds HTN With New Definitions

THURSDAY, July 5, 2018 -- Incorporation of new pediatric hypertension definitions recently published in a clinical practice guideline (CPG) has increased the prevalence of pediatric hypertension in a population of high-risk youth, according to a...

https://ift.tt/2zcNWGq

Viruses ID'd As Most Common Cause of Meningitis in U.K. Adults

THURSDAY, July 5, 2018 -- Viruses are the most commonly identified cause of meningitis among U.K. adults, according to a study published online June 29 in The Lancet Infectious Diseases. Fiona McGill, Ph.D., from the University of Liverpool in the...

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1996 to 2013 Saw Large Increase in Diabetes Spending

THURSDAY, July 5, 2018 -- In 2013, $101 billion was spent in the United States on diabetes, almost a three-fold increase since 1996, according to a study published in the July issue of Diabetes Care. Ellen Squires, M.P.H., from the University of...

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Patients Comfortable With Doctors Having Tattoos, Piercings

THURSDAY, July 5, 2018 -- Patients do not appear to mind if doctors have tattoos or piercings, according to a study published online July 2 in the Emergency Medicine Journal. Marissa Cohen, M.D., from St. Luke's University Health Network in...

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Anticonvulsants Seem to Be Ineffective for Low Back Pain

THURSDAY, July 5, 2018 -- Anticonvulsant drugs are ineffective for chronic low back pain and can cause harm, despite a recent increase in prescribing, according to a review published online July 3 in CMAJ, the journal of the Canadian Medical...

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Marriage May Protect Against Cardiovascular Disease

THURSDAY, July 5, 2018 -- Marital status may influence cardiovascular disease (CVD) risk and prognosis after CVD, according to a review published online June 19 in Heart. Chun Wai Wong, from the University of Keele in the United Kingdom, and...

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For Postpartum Hemorrhage, Carbetocin Similar to Oxytocin

THURSDAY, July 5, 2018 -- For women after vaginal birth, heat-stable carbetocin is non-inferior to oxytocin for prevention of blood loss of at least 500 ml or use of additional uterotonic agents, according to a study published online June 27 in the...

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Characterization of Glycoproteins with the Immunoglobulin Fold by X-Ray Crystallography and Biophysical Techniques

We present approaches for the biophysical and structural characterization of glycoproteins with the immunoglobulin fold by biolayer interferometry, isothermal titration calorimetry, and X-ray crystallography.

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Identification of phenol- and p-cresol-producing intestinal bacteria by using media supplemented with tyrosine and its metabolites

ABSTRACT

To identify intestinal bacteria that produce phenols (phenol and p-cresol), we screened 153 strains within 152 species in 44 genera by culture-based assay using broth media supplemented with 200 µM each of tyrosine and its predicted microbial metabolic intermediates (4-hydroxyphenylpyruvate, DL-4-hydroxyphenyllactate, 3-(p-hydroxyphenyl)propionate, 4-hydroxyphenylacetate and 4-hydroxybenzoate). Phenol-producing activity was found in 36 strains and p-cresol-producing activity in 55 strains. Sixteen strains had both types of activity. Phylogenetic analysis based on the 16S rRNA gene sequences of strains that produced 100 µM or more of phenols revealed that 16 phenol producers belonged to the Coriobacteriaceae, Enterobacteriaceae, Fusobacteriaceae and Clostridium clusters I and XIVa; four p-cresol-producing bacteria belonged to the Coriobacteriaceae and Clostridium clusters XI and XIVa; and one strain producing both belonged to the Coriobacteriaceae. A genomic search for protein homologs of enzymes involved in the metabolism of tyrosine to phenols in 10 phenol producers and four p-cresol producers, the draft genomes of which were available in public databases, predicted that phenol producers harbored tyrosine phenol-lyase or hydroxyarylic acid decarboxylase, or both, and p-cresol producers harbored p-hydroxyphenylacetate decarboxylase or tyrosine lyase, or both. These results provide important information about the bacterial strains that contribute to production of phenols in the intestine.

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Case of chronic pain after laparoscopic percutaneous extraperitoneal closure in an adolescent girl with inguinal hernia in which open repair was effective

Asian Journal of Endoscopic Surgery, EarlyView.


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Surgical outcomes of laparoscopic cholecystectomy for acute cholecystitis in elderly patients

Asian Journal of Endoscopic Surgery, EarlyView.


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Laparoscopic repair of a large perineal hernia after laparoscopic abdominoperineal resection: A case report

Asian Journal of Endoscopic Surgery, EarlyView.


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Minimally invasive abdominal and left thoracic approach for esophagogastric junction adenocarcinoma with esophageal diverticulum: A case report

Asian Journal of Endoscopic Surgery, EarlyView.


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Small bowel obstruction due to internal hernia caused by the ureter after laparoscopic radical cystectomy and ileal conduit: A case report

Asian Journal of Endoscopic Surgery, EarlyView.


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Graft use in the treatment of large and massive rotator cuff tears: an overview of techniques and modes of failure with MRI correlation

Abstract

Despite technical advances, repair of large or massive rotator cuff tears continues to demonstrate a relatively high rate of failure. Rotator cuff repair or superior capsular reconstruction (SCR) using a variety of commercially available grafts provides a promising option in patients with tears that may be at high risk for failure or otherwise considered irreparable. There are three major graft constructs that exist when utilizing graft in rotator cuff repair or reconstruction: augmentation at the rotator cuff footprint, bridging, and SCR. Each construct has a unique appearance when evaluated using postoperative magnetic resonance imaging (MRI), and each construct has unique sites that are predisposed to failure. Understanding the basic principles of these constructs can help the radiologist better evaluate the postoperative MRI appearance of these increasingly utilized procedures.

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Reply: A novel MCM3AP mutation in a Lebanese family with recessive Charcot-Marie-Tooth neuropathy

Sir,

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A novel MCM3AP mutation in a Lebanese family with recessive Charcot-Marie-Tooth neuropathy

Sir,

https://ift.tt/2MPRrVf

CytoTECHnology: The benefits of technology in teaching

Cancer Cytopathology, EarlyView.


https://ift.tt/2u7RWCy

HPV RNA in situ hybridization can inform cervical cytology‐histology correlation

Cancer Cytopathology, EarlyView.


https://ift.tt/2lXVkw5

Dr. Alan S. Rabson, Long-Time NCI Deputy Director and Cancer Research Stalwart, Dies

Many in the cancer research and NIH community are mourning the loss of long-time NCI senior leader Alan Rabson, M.D., who passed away on July 4, at the age of 92. His career spanned 6 decades, including research on tumor virology and cancer pathology and senior NCI leadership roles.

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Cancer prevalence in Pakistan: meta-analysis of various published studies to determine variation in cancer figures resulting from marked population heterogeneity in different parts of the country

Abstract

Background

Pakistan's population is ethnically diverse with distinct ethnic groups inhabiting various parts of the country. Cancer statistics obtained from specific regions populated by distinct ethnic groups may vary considerably. There is no national cancer registry. To determine whether there are indeed significant statistical differences in cancer incidence and prevalence, data was recorded from different parts of Pakistan based on the ethnic composition of the population in those parts.

Methods

Ten papers (original articles) on cancer incidence and prevalence in Pakistan published in the last two decades were selected from PubMed and Google Scholar. Meta-analysis of findings of these studies was performed using Meta-analysis of Observational Studies in Epidemiology (MOOSE) checklist. χ²-based I² test was used for evaluating heterogeneity and Forest plots were generated for calculating unadjusted prevalence estimates. Oral, gastric, prostate, breast, and colorectal cancers were selected for meta-analysis. I² values of 75% or greater indicated high heterogeneity.

Results

All five types of cancer selected for meta-analysis (performed on studies carrying similar statistical weights) showed extremely high heterogeneity with I² values of 99.7% for oral cancer, 98.6% for prostate cancer, 98.3% for gastric cancer, 99.8% for breast cancer, and 85.4% for colorectal cancer. p values for all cancers were highly statistically significant.

Conclusions

Our findings show that the prevalence rates of different cancer types demonstrate marked variation in different studies depending on the place of origin of the study and dominant ethnic group in that region, and these variations are highly statistically significant. A national cancer registry needs to be established as soon as possible.

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Prognostic factors in patients with metastatic spine tumors derived from lung cancer—a novel scoring system for predicting life expectancy

Abstract

Background

Recently, molecule-targeting and bone-modifying agents have improved the treatment outcomes of lung cancer-derived metastatic spine tumors. Therefore, the prognostic factors for such tumors were examined, and novel scoring systems for predicting the life expectancy of patients with such tumors were proposed.

Methods

In 207 patients with lung cancer-derived metastatic spine tumors (surgery 49; conservative therapy 158), we retrospectively examined the factors that influenced the post-treatment survival time (age, sex, the affected site, pathology, general condition, the number of extraspinal bone metastases, the number of spinal metastases, the presence/absence of major internal organ metastasis, paralysis state, the total Tokuhashi score, the serum alkaline phosphatase level, the serum carcinoembryonic antigen level, molecule-targeting drug treatment, and bone-modifying agent treatment). Based on the results, we devised novel scoring systems for predicting the prognosis of such patients.

Results

Univariate analyses showed that the pathology of the primary lung tumor, the patient's general condition and paralysis state, and the presence/absence of molecule-targeting drug treatment significantly influenced survival. We performed a Cox regression analysis of these four factors and developed criteria for a novel scoring system based on the patient's general condition and paralysis state, which exhibited significance in the regression analysis. A retrospective review indicated that the consistency rate between predicted life expectancy and actual survival was 67.3%. When criteria based on the four factors that exhibited significance in the univariate analyses were adopted, the consistency rate was 76.2%.

Conclusion

The patient's general condition and paralysis state, the pathology of the primary lung tumor, and molecule-targeting drug treatment influenced survival among patients with lung cancer-derived metastatic spine tumors. Novel scoring systems based on these four factors were proposed.

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Review of the possible association between thyroid and breast carcinoma

Abstract

Background

Thyroid and breast cancer are two of the malignant diseases with highest incidence in females. Based on clinical experience, breast and thyroid cancer often occur metachronously or synchronously. Therefore, thyroid and breast cancer might share some common etiological factors. The relationship between these diseases has attracted substantial attention, and because these two glands are both regulated by the hypothalamic-pituitary axis, such a relationship is not surprising. A study of this relationship will be useful for obtaining a better understanding of the mechanism by which these two malignancies co-occur.

Main body

This study reviewed the progress in research on the roles of iodine intake, folate metabolism, obesity, gonadal hormones, and thyroid hormone in thyroid and breast cancer. These studies evaluating the etiological roles of these factors in linking breast and thyroid cancer might also improve our understanding and identify new therapeutic approaches, such as sodium/iodide symporter-mediated radioiodine therapy and thyroid-stimulating hormone receptor antagonists, for breast cancer. In addition, some specific treatments for each cancer, such as radiotherapy for breast cancer or radioactive iodine therapy for thyroid cancer, might be risk factors for secondary malignances, including breast and thyroid cancer.

Conclusions

Studies of the precise relationship between the co-occurrence of breast and thyroid cancer will certainly improve our understanding of the biological behaviors of these two malignancies and direct evidence-based clinical practice.

https://ift.tt/2MPyh1K