bluuebunny/crossref_metadata_2025 huggingface dataset:
Knowledge of Clinical Trial Availability and Reasons for Nonparticipation Among Adolescent and Young Adult Cancer Patients
Authors: Shnorhavorian Margarett , Doody David R. , Chen Vivien W. , Hamilton Ann S. , Kato Ikuko , Cress Rosemary D. , West Michele , Wu Xiao-Cheng , Keegan Theresa H.M. , Harlan Linda C. , Schwartz Stephen M.
Published: September 2016

Purpose of the Study:

Adolescent and young adult (AYA) cancer patients are underrepresented in clinical trials, but the reasons for this phenomenon are unknown.

Patients And Methods:

Questionnaire and medical record data from 515 AYA cancer patients (21 acute lymphocytic leukemia [ALL], 201 germ cell tumor, 141 Hodgkin lymphoma, 128 non-Hodgkin lymphoma, 24 sarcoma) from a population-based study were analyzed. We used multivariable models to determine characteristics associated with patient knowledge of the availability of clinical trials for their cancer. Reasons for not participating in a trial were tabulated.

Results:

In total, 63% of patients reported not knowing whether a relevant clinical trial was available, 20% reported knowing that a clinical trial was not available, and 17% reported that a trial was available. Among patients reporting an available trial, 67% were recommended for enrollment. Knowing about the availability of clinical trials was associated with having ALL (odds ratio=2.9, 95% confidence interval=1.1, 7.8). Reporting that a clinical trial was available was positively associated with having ALL, Hodgkin lymphoma, non-Hodgkin lymphoma and sarcoma (relative to germ cell tumor) and working full-time or in school full-time (odds ratio=2.6, 95% confidence interval=1.0, 6.7). Concerns about involvement in research (57%) and problems accessing trials (21%) were the primary reasons cited for not enrolling among patients who knew that a trial was available.

Conclusions:

Improvement in AYA cancer patient clinical trial enrollment will require enhancing knowledge about trial availability and addressing this population’s concerns about participating in medical research.
Stereotactic Ablative Radiotherapy (SABR) for Large Renal Tumors
Authors: Correa Rohann J.M. , Rodrigues George B. , Chen Hanbo , Warner Andrew , Ahmad Belal , Louie Alexander V.
Published: September 2016

Objectives:

Metastatic renal cell carcinoma represents a clinical scenario where aggressive treatment to the primary tumor (ie, cytoreductive nephrectomy) is associated with a survival benefit. We hypothesized that stereotactic ablative radiotherapy (SABR) could be a safe alternative local modality for inoperable metastatic renal cell carcinoma patients. Our study objectives were to report on technical considerations, toxicity, and clinical outcomes of our institutional experience with renal SABR.

Materials and Methods:

Patients who underwent renal SABR at our institution between January 2008 and June 2015 were reviewed. Toxicity was quantified using the Common Terminology Criteria for Adverse Events version 4.0. Radiographic response was evaluated using the Response Evaluation Criteria in Solid Tumors classification. Median overall survival and follow-up were calculated using the Kaplan-Meier and reverse Kaplan-Meier methods, respectively.

Results:

We identified 11 patients that met study criteria. SABR was directed to the tumor or whole kidney in 5 fractions to a dose of 25 to 40 Gy. Median tumor diameter and planning target volume were 9.5 cm (range, 7.5 to 24.4) and 819.3 cm3 (range, 313.4 to 5704.3), respectively. Median follow-up was 3.9 years (95% confidence interval, 0.6-4.9). Five cases of grade 1 toxicity were reported. In the patient with the largest target, grade 2 diarrhea and probable grade 3 nausea were observed. In patients with available follow-up imaging (7/11), stable disease (n=5), partial response (n=1), and progressive disease (n=1) were observed. Median overall survival was 20.4 months (95% confidence interval, 2.30-N/A).

Conclusions:

In this small cohort, renal SABR was delivered with minimal toxicity. A prospective study is underway at our institution to determine maximum tolerable and optimal dosing (NCT02264548).
Evaluating Candidacy for Hypofractionated Radiation Therapy, Accelerated Partial Breast Irradiation, and Endocrine Therapy After Breast Conserving Surgery
Authors: Manyam Bindu V. , Tendulkar Rahul , Cherian Sheen , Vicini Frank , Badiyan Shahed N. , Shah Chirag
Published: September 2016

Purpose/Objective(s):

After breast conserving surgery, adjuvant radiation therapy represents the standard of care for most patients. However, multiple options exist beyond standard fractionated whole breast irradiation including hypofractionated whole breast irradiation (HFRT), accelerated partial breast irradiation (APBI), and endocrine therapy (ET) alone, which can limit treatment duration, and potentially reduce morbidity and cost. Limited data are available on the percentage of patients eligible for these alternatives; therefore, a Surveillance Epidemiology and End Results (SEER) analysis was performed to assess candidacy for these alternative options in women with early stage breast cancer.

Materials and Methods:

Women treated for breast cancer between the years of 2010 and 2012 were identified in the SEER database. Patients with unknown staging, metastatic disease, T3/T4 disease, and ≥N1 disease were excluded. Patients were defined as eligible for HFRT based on the American Society for Radiation Oncology (ASTRO) consensus guidelines and randomised trial testing intensity modulated and partial organ radiotherapy following breast conservation surgery for early breast cancer (IMPORT LOW) trial criteria, APBI based on the ASTRO, American Brachytherapy Society and the Groupe Européen de Curiethérapie of European Society for Therapeutic Radiotherapy and Oncology (GEC-ESTRO) consensus guidelines, and GEC-ESTRO APBI and IMPORT LOW trial criteria, and ET alone based on the Cancer and Leukemia Group B 9343 and Post-operative Radiotherapy in Minimum Risk Elderly II inclusion criteria.

Results:

A total of 108,484 women with early stage breast cancer who met the aforementioned inclusion criteria were identified. Of these patients, 86,896 (80.1%) were eligible for HFRT based on ASTRO consensus guidelines and 81,459 (75.0%) based on IMPORT LOW trial criteria. Regarding APBI, 44,797 (41.2%), 81,020 (74.6%), 81,020 (74.6%) were eligible according to ASTRO, ABS, GEC-ESTRO consensus guidelines, respectively, 97,301 (89.7%) patients according to the GEC-ESTRO trial criteria, and 81,459 (75.0%) patients according to the IMPORT LOW trial criteria. For ET alone, 23,006 (21.2%) were eligible according to Cancer and Leukemia Group B 9343 criteria and 42,104 (38.8%) according to Post-operative Radiotherapy in Minimum Risk Elderly II criteria.

Conclusions:

This SEER analysis demonstrates that a substantial proportion of women with early stage breast cancer are eligible for HFRT, APBI, or ET alone after breast conserving surgery according to consensus guidelines and prospective trial criteria. With incorporation of additional pathologic, dosimetric, and chemotherapy data, quality assurance pathways may use such data to help ensure patients are receiving appropriate risk stratified treatment recommendations.
Vessel Caliber in Normal Tension and Primary Open Angle Glaucoma Eyes With Hemifield Damage
Authors: Rao Aparna , Agarwal Komal , Mudunuri Harika , Padhy Debananda , Roy Avik K. , Mukherjee Sujoy
Published: September 2016

Purpose of the Study:

The purpose of the study was to evaluate retinal vessel diameter in age-matched normal tension glaucoma (NTG) and primary open angle glaucoma (POAG) eyes with hemifield involvement.

Methods:

Fundus photographs of patients with hemifield defect, good visibility of retinal nerve fiber layer defect, and vessels were compared with 30 controls. One eye of each patient (28 NTG and 30 POAG) was randomly chosen for analysis using Image J software by different clinicians at 2 levels. The structural parameters analyzed included retinal nerve fiber layer defect width, diameter of vessels (superotemporal or inferotemporal artery and superotemporal or inferotemporal vein).

Results:

The average superotemporal artery diameter was similar in NTG (71±16.8 µm), POAG (79±26.6 µm), and controls (82±14.1 µm), P=0.2 with similar pattern seen for other vessels. The affected quadrant in all eyes and those with disc hemorrhage (n=8) did not have significantly different arteries and veins diameter as compared with the unaffected quadrant in that eye. No relation of artery or vein diameter with retinal nerve fiber layer defect width or clinical variables in NTG or POAG eyes was seen on multivariate regression analysis.

Conclusions:

The vessel diameter was not significantly different in the affected and unaffected quadrants of age and severity-matched NTG and POAG eyes with hemifield structural and functional defect as reported in earlier studies. These results point toward the possibility that vascular diameter changes may not be the cause for glaucomatous changes.
Central Field Index Versus Visual Field Index for Central Visual Function in Stable Glaucoma
Authors: Rao Aparna , Padhy Debananda , Mudunuri Harika , Roy Avik K. , Sarangi Sarada P. , Das Gopinath
Published: September 2016

Objective:

To compare the variability of central field index (CFI) versus visual field index (VFI) in stable glaucoma with central fixation involvement.

Materials and Methods:

For this retrospective study, we identified multiple visual fields (VFs) of patients with repeatable central fixation involvement on Humphrey VFs (24-2 and 10-2 program) which were stable (clinically and on VFs) over a very short period of 2 to 3 months. The VFI and CFI were calculated as described in earlier reports. We graded the fields as early [mean deviation (MD)>−6 dB], moderate (−6.1 to −12 dB), and severe glaucoma (<−12 dB) based on MD on 24-2 program. The variability of CFI and VFI between visits and across different severity of glaucoma was compared. Relation of the divergence to field indices and clinical parameters were assessed.

Results:

The intervisit difference for VFI was greater than CFI ranging from −4% to 9% versus −1% to 8% in early (P=0.9), −13% to 18% versus −6% to 17% (P=0.056) in moderate, and −21% to 19% versus −9% to 9% (P<0.001) in severe glaucoma. The CFI within each group had narrower range than VFI with maximum range in severe glaucoma (33% to 95%). The divergence of CFI from VFI started at MD 24-2 beyond (worse) −10 dB. This difference between CFI and VFI was associated significantly with number of points with P<1% on 24-2 (R
2=80.3%).

Conclusions:

CFI is less variable than VFI in stable eyes with fixation involvement especially in severe glaucoma indicating need for incorporating CFI calculation for monitoring advanced disease in eyes with central defects.
Pain quality descriptors in community-dwelling older adults with nonmalignant pain
Authors: Thakral Manu , Shi Ling , Foust Janice B. , Patel Kushang V. , Shmerling Robert H. , Bean Jonathan F. , Leveille Suzanne G.
Published: September 2016

This study aimed to characterize the prevalence of various pain qualities in older adults with chronic nonmalignant pain and determine the association of pain quality to other pain characteristics namely: severity, interference, distribution, and pain-associated conditions. In the population-based MOBILIZE Boston Study, 560 participants aged ≥70 years reported chronic pain in the baseline assessment, which included a home interview and clinic exam. Pain quality was assessed using a modified version of the McGill Pain Questionnaire (MPQ) consisting of 20 descriptors from which 3 categories were derived: cognitive/affective, sensory, and neuropathic. Presence of ≥2 pain-associated conditions was significantly associated with 18 of the 20 pain quality descriptors. Sensory descriptors were endorsed by nearly all older adults with chronic pain (93%), followed by cognitive/affective (83.4%) and neuropathic descriptors (68.6%). Neuropathic descriptors were associated with the greatest number of pain-associated conditions including osteoarthritis of the hand and knee. More than half of participants (59%) endorsed descriptors in all 3 categories and had more severe pain and interference, and multisite or widespread pain than those endorsing 1 or 2 categories. Strong associations were observed between pain quality and measures of pain severity, interference, and distribution (P < 0.0001). Findings from this study indicate that older adults have multiple pain-associated conditions that likely reflect multiple physiological mechanisms for pain. Linking pain qualities with other associated pain characteristics serve to develop a multidimensional approach to geriatric pain assessment. Future research is needed to investigate the physiological mechanisms responsible for the variability in pain qualities endorsed by older adults.
Musculoskeletal complaints while growing up from age 11 to age 14: the PIAMA birth cohort study
Authors: Picavet H. Susan J. , Berentzen Nina , Scheuer Ninotsjka , Ostelo Raymond W.J.G. , Brunekreef Bert , Smit Henriette A. , Wijga Alet
Published: September 2016

For musculoskeletal complaints (MSCs) among adults, several risk factors are known, but the most important determinant is an earlier episode of MSCs. Research has shifted to younger ages, showing a high prevalence of MSCs among children and adolescents. Our purpose was to evaluate the prevalence of MSCs among those growing up from age 11 to 14 and to explore the role of several sociodemographic, growth and development, psychosocial, and lifestyle factors. Data collected at age 11 (n = 2651) and age 14 (n = 2522) in the ongoing Dutch Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort study were used. Analyses included multiple logistic regression analyses using stepwise backward selection. The 1-year prevalence of any MSCs for at least 1 month increased from 15.8% at age 11 to 24.4% at age 14, and this was also found for upper extremity complaints (from 4.7% to 7.6%), back complaints (from 2.7% to 9.3%), and lower extremity complaints (from 11.9% to 14.7%). More MSCs were found among girls, those with sports injuries, those with sleeping problems, and those with daytime tiredness, although complaints at age 11 were by far the most important factor associated with MSCs at age 14 for all pain sites. This study showed that MSC is already common at an early age and that already at age 14 the factor with the strongest association is an earlier episode of MSCs. Sleeping problems and tiredness may also play a role in the early development of MSCs, either as determinant or as a consequence.
Celiac Disease is Misdiagnosed Based on Serology Only in a Substantial Proportion of Patients
Authors: Vavricka Stephan R. , Stelzer Teresa , Lattmann Jaqueline , Stotz Matthias , Lehmann Romina , Zeitz Jonas , Scharl Michael , Misselwitz Benjamin , Pohl Daniel , Fried Michael , Tutuian Radu , Fasano Alessio , Schoepfer Alain M. , Rogler Gerhard , Biedermann Luc , Greuter Thomas
Published: September 2016

Background:

Although the diagnostic process in celiac disease (CeD) has been addressed in several international guidelines, little is known about the actual proceeding in current clinical practice. This study investigated the initial presentation, the diagnostic process, follow-up evaluations, and adherence to a gluten-free diet in CeD patients in a real-life setting in Switzerland from a patient’s perspective.

Methods:

We performed a large patient survey among unselected CeD patients in Switzerland.

Results:

A total of 1689 patients were analyzed. The vast majority complained of both gastrointestinal and nonspecific symptoms (71.5%), whereas 1.8% reported an asymptomatic disease course. A total of 35.8% CeD patients were diagnosed by a nongastroenterologist. The diagnostic process differed between nongastroenterologists and gastroenterologists, with the latter more often using duodenal biopsy alone or in combination with serology (94.7% vs. 63.0%) and nongastroenterologists more frequently establishing the diagnosis without endoscopy (37.0% vs. 5.3%, P<0.001). Follow-up serology after 6 months was performed only in half of all patients (49.4%), whereas 69.9% had at least 1 follow-up serology within the first year after diet initiation. About 39.7% had a follow-up endoscopy with duodenal biopsies (after a median of 12 mo; range, 1 to 600 mo). The likelihood of receiving any follow-up examination was higher in patients initially diagnosed by a gastroenterologist.

Conclusions:

A significant proportion of CeD patients are diagnosed by nongastroenterologists. Under the diagnostic lead of the latter, more than a third of the patients receive their diagnosis on the basis of a positive serology and/or genetics only, in evident violation of current diagnostic guidelines, which may lead to an overdiagnosis of this entity.
Linkages Between Patient-centered Medical Homes and Addiction Treatment Organizations
Authors: D’Aunno Thomas , Pollack Harold , Chen Qixuan , Friedmann Peter D.
Published: September 2016

Background:

To meet their aims of providing comprehensive and coordinated care, patient-centered medical homes (PCMHs) need to coordinate services for individuals with substance use disorders. Yet, the 14,000 addiction treatment (AT) organizations across the United States that provide services for more than 1 million individuals daily are generally ill-prepared to work with PCMHs (eg, AT organizations often lack electronic health records).

Objectives:

To examine the extent to which AT organizations have formal linkages through contracts with PCMHs; to identify key dimensions of linkages between PCMHs and AT organizations (eg, shared use of electronic health records); to identify characteristics of AT organizations and their environments associated with these linkages.

Materials and Methods:

We draw on data from a 2014 nationally representative survey of directors and clinical supervisors from 695 AT organizations (n=1390 survey respondents).

Results:

Thirty-eight percent of patients across the nation are receiving treatment in AT organizations linked by contracts to PCMHs. This number increases to 51% in states that expanded Medicaid (vs. only 6.2% of patients in non-Medicaid expansion states). Yet, the great majority of linkages are relatively weak; they do not include the exchange of patient information. Results from multivariable analyses show that larger, nonprofit and publicly owned AT organizations, as well as those located in the northeast and in states that expanded Medicaid coverage, are more likely to have contracts with PCMHs.

Conclusions:

Without stronger linkages between AT organizations and PCMHs or the development of other models that integrate services, individuals with substance abuse disorders may continue to receive uncoordinated care.
A Race to the Top? Competitive Pressure and Magnet Adoption Among US Hospitals 1997–2012
Authors: Richards Michael R. , Lasater Karen , McHugh Matthew
Published: September 2016

Background:

Care quality continues to be a focal point within US health care. One quality innovation is the Magnet recognition program for hospitals, which is a nurse-driven initiative emphasizing care and patient-safety improvements. To date, Magnet hospitals have been associated with better outcomes, but their distribution is highly uneven. Relatedly, little research has characterized what factors drive Magnet adoption (eg, competitive pressure from other hospitals).

Objective:

To examine if hospitals respond to more competing hospitals becoming Magnets by also becoming Magnet institutions.

Research Design:

We use longitudinal data from the American Hospital Association, 1997–2012, and estimate hospital-level fixed-effect regressions to capture the association between Magnet adoption among competitors and a hospital’s own likelihood of becoming a Magnet. We also explore heterogeneity in the relationships according to a hospital’s standing within its market.

Results:

Having more competitors become Magnets strongly predicts that a given hospital seeks Magnet recognition; yet, a hospital’s market position and prevailing competition levels are moderating influences.

Conclusions:

A large literature links Magnet hospitals with better outcomes for patients and nurses, and more recent evidence suggests a business case for becoming a Magnet. We find evidence that hospitals seem motivated by competitive pressure, which suggests economic considerations in the decision to invest in costly care improvements.
A review of postsurgical dysphagia in nonmalignant disease
Authors: Vansant Mathew B. , Kunduk Melda , McWhorter Andrew J.
Published: September 2016

Purpose of review

This article reviews current literature regarding postsurgical dysphagia in nonmalignant disease examining the current recommendations, risk factors, and potential implications.

Recent findings

Surgical interventions including anterior cervical spine surgery, thyroidectomy, laryngeal and pulmonary, cardiac, esophageal and fundoplication, gastric and bariatric, and posterior fossa surgeries are known to result in swallowing dysfunction. Postsurgical dysphagia may increase the length of hospitalization, overall cost, risk of pneumonia, and time to oral intake. There are limited prospective research studies examining postsurgical dysphagia and poorly understood causes. The results are unclear regarding severity, symptom type, duration, and treatment outcomes of postsurgical dysphagia.

The life-changing and life-threatening nature of dysphagia make this an important factor to consider and discuss with patients and families. Both acute and late-onset dysphagia may become chronic if left untreated. Presurgery and postsurgery swallow studies should be considered for cervical spine, thyroid, lung, gastric, cardiac, and surgeries involving the cranial nerves. Future research should examine postsurgical dysphagia in a prospective manner using established and reliable methods of measurement to parse out causal factors and more accurate prevalence rates for each surgical intervention and population.
Pharyngoesophageal diverticuli: diagnosis, incidence and management
Authors: Little Ryan E. , Bock Jonathan M.
Published: September 2016

Purpose of review

Pharyngoesophageal diverticuli such as Zenker's diverticulum are relatively rare diseases that may have a significant impact on a patient's quality of life. Open surgical techniques have historically been the mainstay of treatment for Zenker's diverticuli and remain the preferred approach for many surgeons operating on Killian–Jamieson diverticuli (KJD) and pharyngoceles. However, advances in technology in recent decades have allowed for the development of successful endoscopic surgical techniques for the management of these conditions.

Recent findings

Endoscopic management of Zenker's diverticulum with carbon dioxide laser-assisted diverticulotomy or endoscopic stapler-assisted diverticulostomy has gained wide acceptance in recent years. This is based on studies showing high rates of successful outcomes, low rates of complications and shorter operative time with an associated impact on overall cost and patient recovery. Endoscopic management of KJD and pharyngoceles has recently been described, but remains controversial with many surgeons preferring open surgical approaches for the ability to identify and protect the recurrent laryngeal nerve.

Open and endoscopic techniques are accepted for the treatment of Zenker's diverticulum with open approaches remaining the traditional technique for management of non-Zenker's diverticulum. Further investigation of endoscopic approaches for management of KJD is necessary to assess safety and efficacy.
The differential diagnosis of Rickettsia prowazeki infection
Authors: Vanya Melinda , Hajdu Edit , Szucs Zoltan , Szili Karoly
Published: September 2016

Introduction:

We describe a rare case of Rickettsia prowazeki infection in male prisoners.

Objective:

Our aim was to demonstrate a case of R. prowazeki infection in male prisoners presenting fever, dermatitis, and significant weight loss.

Case:

We report the cases of male prisoners, aged 46, who developed progressive dermatitis, fever, and weight loss. Due to dermatitis and 38.4°C fever, we transferred the prisoners to the Department of Dermatology and Allergology, University of Szeged. The examination of the antigen test was negative for Plasmodium vivax, and biopsy was performed to exclude the vasculitis. For the potentially autoimmune cause of disease choloquine, antihistamine, methyl-prednisolone treatment was ordered. The dermaticological symptoms had progressed; therefore, we sent the patients to the Department of Infectology of Szeged and St Laszlo Hospital for further diagnosis.

The serological tests were positive for R. prowazeki. Following 10-day course of doxycycline treatment, the patients displayed a significant clinical improvement.

Conclusion:

According to our knowledge, this is the first study to report the case of R. prowazeki in Central Europe.
Facilitators of and Barriers to Gastric Cancer Screening Among Korean Americans
Authors: Sin Mo-Kyung , Kim Il-Ho
Published: September 2016

Background:

Gastric cancer is the most highly prevalent cancer among Korean Americans, occurring at a higher rate than among other Asian Americans and non-Latino Whites. However, little is known about the culturally specific barriers to gastric cancer screening among Korean Americans.

Objective:

The aim of this study was to explore facilitators of and barriers to gastric cancer screening among Korean Americans.

Methods:

In this qualitative focus group study, a convenience sample of 50 Korean Americans aged 21 to 75 years was recruited from the Puget Sound area of Washington with the assistance of Korean churches. Five focus groups of 6 to 8 and 1 focus group of 13 were conducted in a church, a café, and an apartment community center. The focus group discussions lasted approximately 30 minutes to 1 hour. Directed content analysis was used to analyze the data.

Results:

Facilitators included exposure to Korean media, history and prevalence of gastric problems, perceptions concerning positive aspects of the healthcare system in South Korea, physician recommendations, technology, and church health fair. Barriers included a lack of knowledge, finance/lack of health insurance, fear of test results, perceptions of an inconvenient American healthcare system, a lack of knowledge of American healthcare providers on culturally related health risks, a dislike of medical procedures, and no preventive measures.

Conclusions:

Sociocultural facilitators and barriers add new knowledge in a field with scarce information available.

Implications for Practice:

The study findings lay the groundwork for developing culturally relevant interventions that enhance healthcare providers’ awareness while empowering Korean Americans to prevent gastric cancer.
NRASQ61R Mutation-specific Immunohistochemistry Also Identifies the HRASQ61R Mutation in Medullary Thyroid Cancer and May Have a Role in Triaging Genetic Testing for MEN2
Authors: Reagh Jessica , Bullock Martyn , Andrici Juliana , Turchini John , Sioson Loretta , Clarkson Adele , Watson Nicole , Sheen Amy , Lim Grace , Delbridge Leigh , Sidhu Stan , Sywak Mark , Aniss Ahmad , Shepherd Phillip , Ng Daniel , Oei Paul , Field Michael , Learoyd Diana , Robinson Bruce G. , Clifton-Bligh Roderick J. , Gill Anthony J.
Published: September 2016

A quarter of patients with medullary thyroid carcinoma (MTC) have germline mutations in the RET proto-oncogene indicating MEN2. Therefore genetic testing is recommended for all patients presenting with MTC. Approximately 40% of MTCs have somatic RET mutations. Somatic mutations in the RAS genes are the next most common driver mutations and appear to be mutually exclusive with germline RET mutation. The single most common somatic RAS mutation is HRASQ61R (c.182A>G), reported in 4.6% to 11% of all MTCs. Mutation-specific immunohistochemistry (IHC) initially developed to identify the NRASQ61R mutation in melanoma (clone SP174) has proven highly sensitive and specific. Because the amino acid sequences for the HRAS and NRAS proteins at codon 61 are identical, we postulated that SP174 IHC would also identify the somatic HRASQ61R mutation. IHC with SP174 was performed on a tissue microarray of 68 patients with MTC including 13 (22.8%) with molecularly confirmed MEN2. Seven (10.3%) MTCs demonstrated positive staining. Six of these patients had already undergone germline RET mutation testing as part of clinical care and were all confirmed to be wild type, excluding the diagnosis of MEN2. All SP174 immunohistochemically positive MTCs were proven to have HRASQ61R mutation (and lack KRASQ61R and NRASQ61R) by Sanger sequencing. All MEN2 patients showed negative staining. We conclude that IHC with SP174 is highly specific for the HRASQ61R mutation in MTC. Because current data suggest that this mutation is mutually exclusive with germline RET mutation, IHC may also have a role in triaging formal genetic testing for MEN2.
Robotic Pancreaticoduodenectomy: Operative Steps (With Video)
Authors: Memeo Riccardo , Tzedakis Stylianos , de Blasi Vito , Dehlawi Ammar , Untereiner Xavier , Rodriguez Maylis , Mutter Didier , Marescaux Jacques , Pessaux Patrick
Published: September 2016

Robotic pancreaticoduodenectomy represents actually an emerging procedure for robot-assisted surgery. Considering complexity, extensive dissection, and difficult restoration of the digestive continuity, it remains a challenge for surgeons. The embedded video (Supplemental Digital Content 1, http://links.lww.com/SLE/A146) reports our standardized technique for robotic pancreaticoduodenectomy. In conclusion, robotic pancreaticoduodenectomy is feasible and can be safely performed. Further evaluation with clinical trials is required to validate its real benefits.
Sensitivity and Specificity of Fractal Analysis to Distinguish Between Healthy and Pathologic Rectal Mucosa Microvasculature Seen During Colonoscopy
Authors: Gryglewski Andrzej , Henry Brandon M. , Mrozek Marian , Żelawski Marcin , Piech Krzysztof , Tomaszewski Krzysztof A.
Published: September 2016

Purpose:

Conventional endoscopy is limited by human capability to recognize and to differentiate pathology. Fractal analysis of blood vessels has been used in other organs, such as the retina, but never before to supplement colonoscopy. The aim of this study was to assess whether it is possible to differentiate between healthy and pathologic rectal mucosa using fractal analysis of the mucosal microvascular architecture seen during colonoscopic examination (Supplemental Digital Content 1, http://links.lww.com/SLE/A145).

Methods:

A total of 300 consecutive patients, 133 females and 167 males with a mean age of 49.1 (±11.3) years, undergoing endoscopy were included in the prospective cohort study. Colonoscopy of the sigmorectal region was performed, and then analyzed with computer-assisted image fractal analysis.

Results:

Fractal analysis of mucosal vasculature allowed for differentiation between healthy and pathologic rectal mucosa, as well as different pathologies (P<0.0001). The sensitivity of fractal analysis to diagnose rectal neoplasia was 92.8% to 96.4%, while the specificity was 91.9% to 98.5% depending on the fractal parameter. The sensitivity of fractal analysis to diagnose rectal colitis was 84.2% to 92.1%, while the specificity was 95.0% to 96.0%, depending on the fractal parameter.

Conclusions:

Computer-assisted fractal analysis allows for differentiation between healthy and pathologic rectal mucosa, as well as between different mucosal pathologies, seen during colonoscopy. Fractal analysis improves the sensitivity and specificity of colonoscopy to aid in the diagnosis of neoplasia or colitis, and should be included in the screening and surveillance of these pathologies.
Caregivers burden in palliative care patients: a problem to tackle
Authors: Veloso Verónica Inés , Tripodoro Vilma Adriana
Published: September 2016

Purpose of review

To revise the family caregiver's burden concept and to understand the implications for the patient, family and healthcare system. We analyzed recent literature in three main areas: the role of family caregiver at the end of life, the family caregiver's burden and the involvement of social care networks.

Recent findings

The family caregiver often accepts the caring as a natural action, presumably imposed by the society. A recent review described seven main roles of care which, according to family system and society, consist of different tasks and activities. To assume this role is not stress free. It is likely to develop a ‘burden’ by the assumed task.

Family members who are close to the patient may play the role of caregiver, well-being enhancer, diversity of tasks fulfiller, minimizer and managing suffering, palliative care facilitator and responsible for the continuity of care, apprentice and participant of health teams. The family caregiver often gives priority to the problems of his dependent family member, becoming almost ‘invisible’ to the health system. It should also be consider the relevance of this issue into future bereavement process. Considering all these aspects, the family caregiver is often considered by the healthcare teams as ‘overall tasks’ performers’.
Efficacy of FemiScan Pelvic Floor Therapy for the Treatment of Urinary Incontinence
Authors: Segal Shimon , Morse Abraham , Sangal Purnima , Hirsch Nathan , Kohli Neeraj
Published: September 2016

Objectives

Pelvic floor muscle training can be effective in alleviating urinary incontinence; however, women need instruction, motivation, and feedback to gain optimal benefit from pelvic rehabilitation. The Food and Drug Administration–approved FemiScan Pelvic Floor Therapy System uses office electromyography and an in-home programmable device to provide training, motivation, and feedback between office visits. This study was undertaken to document the outcomes of women who completed an MD-supervised program using the FemiScan Pelvic Floor Therapy System.

Methods

In this chart review, women with urinary incontinence, who completed the 8-visit protocol, were included in the analysis. We collected patient demographics, electromyographic measurements, and responses to subjective questions about the status of their urinary incontinence symptoms.

Results

Two hundred fifteen (60%) of 361 patients who started treatment with FemiScan completed the 8-visit protocol. No adverse events were reported. The mean age was 54.4 ± 12.7 years. There was a statistically significant increase in the mean maximal response comparing the first and final electromyographic measurements obtained during the first and last electromyography office visits. The left side (15.9 ± 10.2 μV vs 28.0± 15.2 μV, P < 001) and the right side (16.6 μV vs 28.2 μV, P < 0.001) were analyzed separately in peak electromyographic measurements between the first and final visits. Seventy-five percent considered their symptoms at least 80% improved with 45% reporting complete subjective cure. Urinary Distress Inventory 6 results confirmed the subjective report with a statistical significant improvement comparing the first and last visit (9.47 ± 3.66 vs 2.71 ± 3.58, P < 001).

Conclusions

FemiScan appears to be a safe and effective treatment for urinary incontinence with concomitant increased pelvic floor electromyographic activity.
Risk Factors for Microscopic Hematuria in Women
Authors: Richter Lee A. , Lippmann Quinn K. , Jallad Karl , Lucas Joelle , Yeung Jennifer , Dune Tanaka , Mellano Erin , Weissbart Steven , Mete Mihriye , Kim Ja-Hong , Gutman Robert
Published: September 2016

Objectives

The objective of this study was to determine the risk factors that may contribute to the diagnosis of microscopic hematuria (MH) in women.

Methods

This multicenter case-control study reviewed cases of women presenting to Female Pelvic Medicine & Reconstructive Surgery sites with MH from 2010 to 2014. Microscopic hematuria was defined as 3 or more red blood cells per high power field in the absence of infection as indicated in the American Urologic Association guidelines. Controls were matched to cases in a 1:1 ratio and chart review of 10 risk factors was performed (urethral caruncle, pelvic organ prolapse, vaginal atrophy, personal or family history of nephrolithiasis, prior prolapse or incontinence surgery, past or current smoking, chemical exposure, family history of urologic malignancy, prior pelvic radiation, and prior alkylating chemotherapy). Odds ratios were performed to assess risk factors.

Results

There were 493 cases and 501 controls from 8 Female Pelvic Medicine & Reconstructive Surgery sites. Current smoking, a history of pelvic radiation, and a history of nephrolithiasis were all significant risk factors for MH (P < 0.05). Vaginal atrophy, menopausal status, and use of estrogen were not found to be risk factors for MH (P = 0.42, 0.83, and 0.80, respectively). When stratifying the quantity of MH, women with increased red blood cells per high power field were more likely to have significant findings on their imaging results.

Conclusions

Our findings suggest that the risk factors for MH in women are current smoking, a history of pelvic radiation, and a history of nephrolithiasis.
Outcomes of Sacral Neuromodulation in Patients with Prior Surgical Treatment of Stress Urinary Incontinence and Pelvic Organ Prolapse
Authors: Bartley Jamie M. , Ramirez Verity , Killinger Kim A. , Boura Judith A. , Gupta Priyanka , Gaines Natalie , Gilleran Jason P. , Peters Kenneth M.
Published: September 2016

Objectives

The aim of this study was to evaluate the efficacy of sacral neuromodulation in patients with prior stress urinary incontinence (SUI) or pelvic organ prolapse (POP) surgery.

Methods

Women in our prospective neuromodulation database were evaluated. Patients with a history of prior SUI/POP surgery were compared to those without. Medical records at baseline were reviewed, and primary outcome was defined as moderate/marked improvement on Global Response Assessment (GRA) at 3 months. Secondary outcomes were measured using bladder diaries and Overactive Bladder Symptom Severity (OABq-SS)/health-related quality of life (HRQOL). Data were analyzed with Pearson χ2 test, Fisher exact test, Wilcoxon rank-sum test, and repeated-measures analyses.

Results

Of 210 subjects, 108 (51%) had prior SUI/POP surgery. Patients with SUI/POP surgery had more prior hysterectomies. At 3 months, there was no difference between groups on GRA outcomes. On the bladder diary, both groups had improvement in median voids per 24 hours, urgency severity, and urge incontinence over 2 years. On the GRA, fewer patients in the SUI/POP group were treatment responders at 12 and 24 months. For urinary urgency, a few in this group were moderately/markedly improved at 6 months, and a higher proportion are reported still leaking urine at 6 and 12 months. Similar proportions in each group reported moderate/marked improvement in leaking. Satisfaction was similar between groups. The OABq-SS/HRQOL scores improved, and there was no difference between the groups.

Conclusion

Sacral neuromodulation improves bladder symptoms in women with prior SUI/POP surgery, but response may be slightly less in those with prior surgery due to underlying bladder or pelvic floor issues.
Re-Treatment With Ethambutol After Toxic Optic Neuropathy
Authors: Bouffard Marc A. , Nathavitharana Ruvandhi R. , Yassa David S. , Torun Nurhan
Published: September 2016

There are no data in the literature regarding the safety of re-treatment with ethambutol for recurrent mycobacterial infection after prior ethambutol-induced optic neuropathy. We describe a patient who developed optic neuropathy attributed to ethambutol, recovered fully after drug withdrawal, and tolerated a 14-month long re-treatment 10 years later without developing recurrent optic neuropathy.
StereoGene: Rapid Estimation of Genomewide Correlation of Continuous or Interval Feature Data
Authors: Stavrovskaya Elena D. , Niranjan Tejasvi , Fertig Elana J. , Wheelan Sarah J. , Favorov Alexander , Mironov Andrey
Published: September 2016

Motivation

Genomics features with similar genomewide distributions are generally hypothesized to be functionally related, for example, co-localization of histones and transcription start sites indicate chromatin regulation of transcription factor activity. Therefore, statistical algorithms to perform spatial, genomewide correlation among genomic features are required.

Results

Here, we propose a method, StereoGene, that rapidly estimates genomewide correlation among pairs of genomic features. These features may represent high throughput data mapped to reference genome or sets of genomic annotations in that reference genome. StereoGene enables correlation of continuous data directly, avoiding the data binarization and subsequent data loss. Correlations are computed among neighboring genomic positions using kernel correlation. Representing the correlation as a function of the genome position, StereoGene outputs the local correlation track as part of the analysis. StereoGene also accounts for confounders such as input DNA by partial correlation. We apply our method to numerous comparisons of ChIP-Seq datasets from the Human Epigenome Atlas and FANTOM CAGE to demonstrate its wide applicability. We observe the changes in the correlation between epigenomic features across developmental trajectories of several tissue types consistent with known biology, and find a novel spatial correlation of CAGE clusters with donor splice sites and with poly(A) sites. These analyses provide examples for the broad applicability of StereoGene for regulatory genomics.

Availability

TheStereoGeneC++ source code, program documentation, Galaxy integration scripts and examples are available from the project homepagehttp://stereogene.bioinf.fbb.msu.ru/

Contact

favorov@sensi.org

Supplementary information

Supplementary data are available online.
Functional consequences of pre- and postsynaptic expression of synaptic plasticity
Authors: Costa Rui Ponte , Mizusaki Beatriz E.P. , Jesper Sjöström P. , van Rossum Mark C. W.
Published: September 2016

Growing experimental evidence shows that both homeostatic and Hebbian synaptic plasticity can be expressed presynaptically as well as postsynaptically. In this review, we start by discussing this evidence and methods used to determine expression loci. Next, we discuss functional consequences of this diversity in pre- and postsynaptic expression of both homeostatic and Hebbian synaptic plasticity. In particular, we explore the functional consequences of a biologically tuned model of pre- and postsynaptically expressed spike-timing-dependent plasticity complemented with postsynaptic homeostatic control. The pre- and postsynaptic expression in this model predicts 1) more reliable receptive fields and sensory perception, 2) rapid recovery of forgotten information (memory savings) and 3) reduced response latencies, compared to a model with postsynaptic expression only. Finally we discuss open questions that will require a considerable research effort to better elucidate how the specific locus of expression of homeostatic and Hebbian plasticity alters synaptic and network computations.
Condensin I-mediated mitotic chromosome assembly requires association with chromokinesin KIF4A
Authors: Takahashi Motoko , Wakai Toshifumi , Hirota Toru
Published: September 2016

The chromokinesin KIF4A has been implicated in shaping mitotic chromosomes, but its functional relationship to condensin complexes remains controversial. Here, we found that, in mitosis, KIF4A associates with condensin I but not with condensin II. Mutational analyses indicated that the enrichment of condensin I to chromosomal axes depends on its association with KIF4A in a way that likely involves its motor activity. Remarkably, this interaction is required for condensin I to confer physiological properties to chromosomes. These observations provide an insight into how condensin I is enriched at chromosomal axes and underscore the significance of axial structure in organizing mitotic chromosomes.
Genetic ablation of Smoothened in pancreatic fibroblasts increases acinar–ductal metaplasia
Authors: Liu Xin , Pitarresi Jason R. , Cuitiño Maria C. , Kladney Raleigh D. , Woelke Sarah A. , Sizemore Gina M. , Nayak Sunayana G. , Egriboz Onur , Schweickert Patrick G. , Yu Lianbo , Trela Stefan , Schilling Daniel J. , Halloran Shannon K. , Li Maokun , Dutta Shourik , Fernandez Soledad A. , Rosol Thomas J. , Lesinski Gregory B. , Shakya Reena , Ludwig Thomas , Konieczny Stephen F. , Leone Gustavo , Wu Jinghai , Ostrowski Michael C.
Published: September 2016

The contribution of the microenvironment to pancreatic acinar-to-ductal metaplasia (ADM), a preneoplastic transition in oncogenic Kras-driven pancreatic cancer progression, is currently unclear. Here we show that disruption of paracrine Hedgehog signaling via genetic ablation of Smoothened (Smo) in stromal fibroblasts in a KrasG12D mouse model increased ADM. Smo-deleted fibroblasts had higher expression of transforming growth factor-α (Tgfa) mRNA and secreted higher levels of TGFα, leading to activation of EGFR signaling in acinar cells and increased ADM. The mechanism involved activation of AKT and noncanonical activation of the GLI family transcription factor GLI2. GLI2 was phosphorylated at Ser230 in an AKT-dependent fashion and directly regulated Tgfa expression in fibroblasts lacking Smo. Additionally, Smo-deleted fibroblasts stimulated the growth of KrasG12D/Tp53R172H pancreatic tumor cells in vivo and in vitro. These results define a non-cell-autonomous mechanism modulating KrasG12D-driven ADM that is balanced by cross-talk between Hedgehog/SMO and AKT/GLI2 pathways in stromal fibroblasts.
Binding of nuclear factor κB to noncanonical consensus sites reveals its multimodal role during the early inflammatory response
Authors: Kolovos Petros , Georgomanolis Theodore , Koeferle Anna , Larkin Joshua D. , Brant Lilija , Nikolicć Miloš , Gusmao Eduardo G. , Zirkel Anne , Knoch Tobias A. , van Ijcken Wilfred F. , Cook Peter R. , Costa Ivan G. , Grosveld Frank G. , Papantonis Argyris
Published: September 2016

Mammalian cells have developed intricate mechanisms to interpret, integrate, and respond to extracellular stimuli. For example, tumor necrosis factor (TNF) rapidly activates proinflammatory genes, but our understanding of how this occurs against the ongoing transcriptional program of the cell is far from complete. Here, we monitor the early phase of this cascade at high spatiotemporal resolution in TNF-stimulated human endothelial cells. NF-κB, the transcription factor complex driving the response, interferes with the regulatory machinery by binding active enhancers already in interaction with gene promoters. Notably, >50% of these enhancers do not encode canonical NF-κB binding motifs. Using a combination of genomics tools, we find that binding site selection plays a key role in NF-κΒ–mediated transcriptional activation and repression. We demonstrate the latter by describing the synergy between NF-κΒ and the corepressor JDP2. Finally, detailed analysis of a 2.8-Mbp locus using sub-kbp-resolution targeted chromatin conformation capture and genome editing uncovers how NF-κΒ that has just entered the nucleus exploits pre-existing chromatin looping to exert its multimodal role. This work highlights the involvement of topology in cis-regulatory element function during acute transcriptional responses, where primary DNA sequence and its higher-order structure constitute a regulatory context leading to either gene activation or repression.