bluuebunny/crossref_metadata_2025 huggingface dataset:
A Simple Tool Using AM-PAC “6-Clicks” to Measure Value Added in Acute Care Physical Therapy: The Therapy Value Quotient
Authors: Hull Brian L. , Thut M. Cathy
Published: May 2018

Background and Purpose:

Acute physical therapy practitioners and leaders continue to search for a practical method to measure value. The purpose of this case report is to introduce the Therapy Value Quotient and its simple yet effective use of Activity Measure for Post-Acute Care Inpatient Mobility Short Form, also known as “6-Clicks,” and common payroll data to measure changes in value added to patient care.

Case Description:

Health care service value should be measured by outcomes produced divided by the cost of services to produce those outcomes. Although acute physical therapy practice continues to progress toward consistent outcome measurement, widespread application of outcomes to quantify value is rare. This lack of value measurement leaves acute care practitioners' value measured primarily in terms of how many units or visits a therapist can code in a certain number of hours worked. Unfortunately, quantities of units or visits are not synonymous with value. Acute care managers and practitioners need a viable and easy-to-use tool that requires minimal data entry and uses existing, easily accessible payroll and electronic health record data.

Outcomes:

The goal of this project was to create a value calculation with commonly used systems (payroll, electronic health record) data and Activity Measure for Post-Acute Care Inpatient Mobility Short Form data to quantify value. Minimizing manual data entry decreases errors and improves real-time calculations. The purposely minimized design of the equation allows clinicians and managers freedom to create highest-value processes that achieve the maximal value added.

Discussion:

The Therapy Value Quotient can help managers and clinicians investigate and measure value-adding tactics while improving care delivery and efficiency instead of simply increasing the number of procedures per hour worked.
Integrating Population Health Data on Violence Into the Emergency Department: A Feasibility and Implementation Study
Authors: Levas Michael N. , Hernandez-Meier Jennifer L. , Kohlbeck Sara , Piotrowski Nancy , Hargarten Stephen
Published: May 2018

Geocoded emergency department (ED) data have allowed for the development and evaluation of novel interventions for the prevention of violence in cities outside of the United States. First implemented in Cardiff, United Kingdom, collection of these data provides public health agencies, community organizations, and law enforcement with place-based information on assaults. The purpose of this study was to assess the feasibility of translating this model within the electronic medical record (EMR) in the United States. A new EMR module based on the Cardiff Model was developed and integrated into the existing ED EMR. Data were collected for all patients reporting an assaultive injury upon arrival to the ED. Emergency department nurses were subsequently recruited to participate in 2 surveys and a focus group to evaluate the implementation and to provide qualitative feedback to enhance integration. Nurses completed EMR questions in 98.2% of patients reporting to the ED over the study period. More than 90% of survey respondents were satisfied with their participation, and most felt that the questions were useful for clinical care (79/70%), were integrated well into workflow (89/90%), and were congruent with the ED and hospital goals and mission (93/98%). Focus group themes centered on ED culture, external factors, and internal workflow. It is feasible to implement place-based, assault-related injury-specific questions into the EMR with minimal disruption of workflow and triage times. Nurses, as key members of the ED team, are receptive to participating in the collection of population health data that may inform community violence prevention activities.
Evaluation of Clinical Outcomes with Phosphodiesterase-5 Inhibitor Therapy for Right Ventricular Dysfunction After Left Ventricular Assist Device Implantation
Authors: Roberts Katherine L. , Shuster Jerrica E. , Britt Nicholas S. , Balsara Keki R. , Graetz Thomas J. , Helwani Mohammad , Itoh Akinobu , Tellor Bethany R.
Published: May 2018

Few studies have evaluated the use of phosphodiesterase-5 inhibitors (PDE5-i) for right ventricular (RV) dysfunction after left ventricular assist device (LVAD) implantation. The study purpose was to examine the impact of postoperative inpatient PDE5-i therapy on clinical outcomes in patients with LVADs. This single-center, retrospective cohort study screened 445 LVAD recipients between January 2011 and May 2015 for eligibility. Subjects receiving post-LVAD PDE5-i were compared with those who did not. The primary outcome was the proportion of all-cause hospital readmission at 30 days. Additional outcomes assessed included duration of intravenous inotrope or inhaled epoprostenol therapy, length of stay, duration of mechanical ventilation, overall survival, and improvement in the degree of postoperative RV dysfunction. Comparative analyses were performed before and after propensity score (PS) matching. Three-hundred and eighteen patients were included; 208 received post-LVAD inpatient PDE5-i and 110 patients did not. There was no difference in the rate of readmission at 30 days before or after PS matching. No significant differences were found between groups with regard to inotrope or epoprostenol duration, lengths of stay, duration of mechanical ventilation, overall survival, or improvement in the degree of RV dysfunction after PS matching. In the current study, the use of PDE5-i for adjunctive treatment of post-LVAD RV dysfunction was not associated with improved clinical outcomes.
Structural brain abnormalities in Cushing's syndrome
Authors: Bauduin Stephanie E.E.C. , van der Wee Nic J.A. , van der Werff Steven J.A.
Published: May 2018

Purpose of review

Alongside various physical symptoms, patients with Cushing's disease and Cushing's syndrome display a wide variety of neuropsychiatric and cognitive symptoms, which are indicative of involvement of the central nervous system. The aim of this review is to provide an overview of the structural brain abnormalities that are associated with Cushing's disease and Cushing's syndrome and their relation to behavioral and cognitive symptomatology.

Recent findings

In this review, we discuss the gray matter structural abnormalities found in patients with active Cushing's disease and Cushing's syndrome, the reversibility and persistence of these changes and the white matter structural changes related to Cushing's syndrome. Recent findings are of particular interest because they provide more detailed information on localization of the structural changes as well as possible insights into the underlying biological processes.

Active Cushing's disease and Cushing's syndrome is related to volume reductions of the hippocampus and in a prefrontal region involving the anterior cingulate cortex (ACC) and medial frontal gyrus (MFG). Whilst there are indications that the reductions in hippocampal volume are partially reversible, the changes in the ACC and MFG appear to be more persistent. In contrast to the volumetric findings, changes in white matter connectivity are typically widespread involving multiple tracts.
Prevalence and incidence of hepatitis delta in patients with chronic hepatitis B in Spain
Authors: Aguilera Antonio , Trastoy Rocio , Rodríguez-Calviño Javier , Manso Tamara , de Mendoza Carmen , Soriano Vicente
Published: May 2018

Background

Hepatitis delta virus (HDV) is a defective agent that only replicates in the presence of the hepatitis B virus. Accordingly, HDV acquisition may occur as superinfection of HBsAg+ carriers or following acute dual HDV and hepatitis B virus exposure. Herein, we examined the global and incident rates of HDV infections in Spain.

Patients and methods

The presence of anti-HDV antibody and new HDV superinfections was examined in all HBsAg+ patients who attended one large tertiary outclinic in Spain since year 2000. Anti-HDV antibodies were tested repeatedly every 5 years in those previously negative.

Results

During a median follow-up of 12 years, 478 individuals were diagnosed as HBsAg+. Overall, 64.4% were male, median age was 55 years, 88.1% were native Spaniards, 6.5% were coinfected with HIV, and 7.3% were reactive for hepatitis C virus (HCV) antibodies.

A total of 19 (4%) patients had anti-HDV antibody at first diagnosis. There were no further HDV seroconversions. Most anti-HDV+ patients were male (n=12), former injection drug users (n=13), and native Spaniards (n=16). Coinfection with HIV was found in six, and 12 had HCV antibodies. Interestingly, three of seven women with delta hepatitis were foreigners (Asian or African), denied injection drug use, were younger than 40 years old, and negative for both HCV and HIV.

Conclusion

The prevalence of chronic hepatitis delta is currently very low (<5%) among chronic HBsAg+ carriers in Spain, with lower rates in recent years. Moreover, new incident HDV infections were not seen in 478 chronic hepatitis B carriers since year 2000, following drastic declines in injection drug use.
Recommendations for Diagnosis and Management of Autoimmune Pancreatitis in Childhood
Authors: Scheers Isabelle , Palermo Joseph J. , Freedman Steven , Wilschanski Michael , Shah Uzma , Abu‐El‐Haija Maisam , Barth Bradley , Fishman Douglas S. , Gariepy Cheryl , Giefer Matthew J. , Heyman Melvin B. , Himes Ryan W. , Husain Sohail Z. , Lin Tom K. , Liu Quin , Lowe Mark , Mascarenhas Maria , Morinville Veronique , Ooi Chee Y. , Perito Emily R. , Piccoli David A. , Pohl John F. , Schwarzenberg Sarah J. , Troendle David , Werlin Steven , Zimmerman Bridget , Uc Aliye , Gonska Tanja
Published: May 2018

Objectives:

Autoimmune pancreatitis (AIP) represents a complex immune‐mediated pancreas disorder. Pediatric AIP (P‐AIP) is rare. We have recently summarized the characteristic features of P‐AIP. We now aim to develop recommendation statements to standardize the diagnostic and therapeutic approach to P‐AIP and facilitate future research in the field.

Methods:

A panel of pediatric gastroenterologists participating in the International Study Group of Pediatric Pancreatitis: In search for a cuRE was formed to discuss and then vote on 15 recommendation statements. A consensus of at least 80% was obtained following 3 voting rounds and revision of the statements.

Results:

We have now generated 15 statements to help standardize the approach to diagnosis and management of P‐AIP.

Conclusions:

The first P‐AIP recommendation statements developed by the International Study Group of Pediatric Pancreatitis: In search for a cuRE group are intended to bring standardization to the diagnosis and treatment of this rare childhood disorder. These statements may help guide a uniform approach to patient care and facilitate future research studies.
Cognitive Profile of Children With Intracranial Germ Cell Tumor According to Tumor Location
Authors: Coutinho Virginie , Dellatolas Georges , Castaignede-Lalande Clemence , Longaud-Vales Audrey , Kieffer Virginie , Guerrini-Rousseau Lea , Grill Jacques , Valteau-Couanet Dominique , Dufour Christelle
Published: May 2018

Purpose:

The purpose of this study was to evaluate the long-term cognitive sequelae and to describe the neuropsychological profile of patients with intracranial germ cell tumors according to tumor location (pineal or suprasellar site).

Patients and Methods:

Forty-five children treated at Gustave Roussy between 1991 and 2010 were assessed with neuropsychological tests to measure IQ, memory, visuospatial, motor, and executive skills at a mean delay of 4.2 years after diagnosis. All patients have received chemotherapy associated with surgery in 17 cases. Thirty-nine patients received, radiotherapy (focal 27, focal plus ventricles 8, craniospinal 4). Twenty-three patients had 2 IQ assessments with a mean delay of 4.1 years between the first and second.

Results:

Full scale IQ was preserved, with higher verbal IQ than other IQ indexes. Visuospatial, fine-motor, and executive difficulties were present in a significant proportion of patients. Visuospatial and fine-motor deficits were significantly associated with oculomotor difficulties, more present in the pineal than in the suprasellar group. No cognitive decline was observed between the first and the second IQ assessment.

Conclusions:

Overall cognitive abilities were preserved in children treated for central nervous system germ cell tumor.
Composite Adrenocortical Carcinoma and Neuroblastoma in an Infant With a TP53 Germline Mutation: A Case Report and Literature Review
Authors: Tang Yue-Jia , Yu Ting-Ting , Ma Jing , Zhou Ying , Xu Min , Gao Yi-Jin
Published: May 2018

Li-Fraumeni syndrome is a kind of hereditary cancer predisposition syndromes, and is caused by TP53 gene mutation. Adrenocortical carcinoma (ACC) is commonly described as the most closely related tumor with this disease. Here, we present a case of a male infant with composite ACC and neuroblastoma who inherited a TP53 gene mutation from his mother, a 20-year-old carrier without any tumor to date. This TP53 gene mutation may be pathogenic and lead to composite malignancies of ACC and neuroblastoma.
Hemophagocytic Lymphohystiocytosis Associated With Type Ia Glycogen Storage Disease
Authors: Düzenli Kar Yeter , Özdemir Zeynep C. , Kiral Eylem , Kiliç Yildirim Gonca , Dinleyici Ener Ç. , Bör Özcan
Published: May 2018

Background:

Hemophagocytic lymphohystiocytosis (HLH) is characterized by fever, splenomegaly, pancytopenia, and elevated levels of triglycerides and ferritin. These signs and symptoms are common to other metabolic diseases.

Observation:

A 5-month-old female infant, who presented with fever, respiratory distress, massive hepatomegaly, and bicytopenia, was diagnosed as having HLH and chemotherapy was initiated. The patient was negative for familial HLH gene mutations. Respiratory distress and laboratory findings improved rapidly after starting chemotherapy. However, there was no improvement in the massive hepatomegaly and she experienced hypoglycemic episodes. In addition, her family history included a cousin with glycogen storage disease (GSD). On the basis of the findings, the patient was diagnosed as having type Ia GSD. There are no previous reports of HLH secondary to GSD type Ia in the literature.

Conclusions:

Congenital metabolic diseases should be considered in the differential diagnosis of children with HLH.
Adherence to American Cancer Society Guidelines on Nutrition and Physical Activity in Female Cancer Survivors
Authors: Park So-Hyun , Knobf M. Tish , Kerstetter Jane , Jeon Sangchoon
Published: May 2018

Background

The American Cancer Society (ACS) publishes guidelines on nutrition and physical activity to minimize health risks in cancer patients and survivors. Studies show that high adherence to such guidelines is associated with a decrease in overall cancer incidence and mortality. However, there are sparse data on adherence to the ACS guidelines in cancer survivors.

Objective

The aim of this study was to describe adherence to the ACS guidelines in female cancer survivors who participated in an exercise intervention trial for 1 year.

Methods

Perimenopausal and early postmenopausal female cancer survivors (n = 154) participated in a randomized controlled trial that examined the efficacy of an aerobic-resistance exercise intervention. In addition to body mass index and alcohol, diet and physical activity data were collected with 4-day diet records and the International Physical Activity Questionnaire. A scoring system was used to determine adherence to the ACS guidelines, with scores ranging from 0 (no adherence) to 8 (highest adherence).

Results

Mean total adherence scores for ACS guidelines for all intervention and control condition participants, most of whom had breast or gynecological cancers, were 4.2 (baseline), 4.9 (6 months), and 4.8 (12 months), suggesting moderate adherence. Physical activity levels improved in both groups; however, no significant change was observed for adherence to weight, dietary, or alcohol intake guidelines for either group.

Conclusion

Findings indicate only partial adherence to the ACS guidelines, even for motivated cancer survivors participating in an exercise intervention study.

Implications for Practice

Further research is needed regarding strategies and interventions to improve adherence to ACS guidelines.
Management and Outcome of Pediatric Patients With Transient Small Bowel–Small Bowel Intussusception
Authors: Melvin Jennifer E. , Zuckerbraun Noel S. , Nworgu Chijindu R. , Mollen Kevin P. , Furtado Andre D. , Manole Mioara D.
Published: May 2018

Objective

The aim of this study was to assess the management and outcomes of healthy pediatric patients diagnosed radiologically with transient and benign small bowel–small bowel intussusception (SB-SBI).

Methods

Retrospective cohort study of healthy patients 0 to 18 years of age who presented to a children's hospital emergency department from January 1, 2005, to June 30, 2015, and had transient and benign SB-SBI characterized by spontaneous resolution (ie, transient), diameter of less than 2.5 cm, no lead point, normal bowel wall thickness, nondilated proximal small bowel, and no colonic involvement (ie, benign radiographic features). Charts were reviewed for demographics, clinical presentation, radiologic studies obtained, outcomes, and further management. Medical and radiologic records were also reviewed for 1 year after presentation for any subsequent pathologic diagnoses.

Results

Sixty-eight patients were included in our study, with a total of 87 episodes of transient and benign SB-SBI on initial or follow-up examination. Overall, 39 patients (57%) were admitted to the hospital, and 38 patients (56%) had a surgical consultation. Twenty-four patients (35%) had further radiologic studies obtained, including computed tomography scans, esophagogastroduodenoscopy, Meckel’s scan, barium swallow studies, and magnetic resonance imaging. All studies were negative for concerning pathology including apparent lead points. None of the patients required surgical intervention or had any complications.

Conclusions

Transient and benign SB-SBIs with reassuring radiologic and clinical features diagnosed in healthy pediatric patients are likely incidentally found and are unlikely to be associated with a pathologic lead point.
Insufficient and Scant Endometrial Samples: Determining Clinicopathologic Outcomes and Consistency in Reporting
Authors: Goebel Emily A. , McLachlin C. Meg , Ettler Helen C. , Weir Michele M.
Published: May 2018

There are no widely accepted pathologic criteria for reporting endometrial samples with limited tissue and no consensus on the clinical follow-up of patients with these samples. Our study compares clinicopathologic outcomes and determines reporting consistency for these samples. This was done in 3 parts: (1) retrospective chart review of all patients with reported insufficient or scant endometrial samples from 2010 to 2013 at our center to determine repeat sampling and final pathologic diagnosis; (2) survey of gynecologists about their practice for managing patients with these samples; (3) blind review of 99 cases of previously reported scant or insufficient samples in which 4 reviewers separately reassigned cases as scant, insufficient, or diagnostic. Agreement was determined across reviewers. For part (1): 1149 patients had insufficient (49%) or scant (51%) samples with no significant difference in repeat biopsy rate (33% vs. 31%; P=0.33). Final diagnosis of uterine malignancy was higher in patients with a previous insufficient sample than with scant (19% and 9%, respectively), but this was not statistically significant. For part (2): among gynecologists surveyed, 4 of 5 reported managing patients with insufficient or scant samples similarly. For part (3): complete consensus across raters occurred in 57% of cases (Fleiss κ, 0.4891). Similar repeat biopsy rates between scant and insufficient samples suggest that our clinicians choose similar management for both terminologies. As such, distinction between insufficient and scant samples may not be necessary in pathologic reporting. Given the malignancy outcomes, both groups merit repeat sampling in the appropriate context.
Comprehensive Surgical Staging in Stage 1 Clear Cell and Endometrioid Ovarian Carcinomas: Is it Necessary?
Authors: Padhy Radha R. , Savage Johanna , Kurman Robert J.
Published: May 2018

The objective of this article was to evaluate the presence of occult metastasis after comprehensive surgical staging of clear cell ovarian carcinoma (CCC) and endometrioid ovarian carcinoma (EMCA) that appeared to be confined to the ovary at time of surgery. Between 1998 to 2016, 85 patients with CCC and EMCA were identified who were comprehensively staged and felt to be stage 1 intraoperatively. Of the 85 patients who underwent surgical staging, 4 (4.7%) had omental and dense pelvic side-wall tumor adhesions. On final pathology, 67 (79%) patients were diagnosed as stage 1A of which 29 (43%) patients were upstaged to 1C1 due to intraoperative rupture. The remaining 18 (21%) patients were staged as 1C2/1C3. The 1- and 5-yr disease-free survival for pathology stage 1A tumors was 94% and 76%, respectively, and for 1C2/1C3 tumors was 100% and 75%, respectively. Among patients who received adjuvant chemotherapy, the 5-yr disease-free survival was near equal for pathology stage 1A and 1C2/1C3 groups (73% vs. 74%), with a lower 5-yr disease-free survival for CCC compared with EMCA (72% vs. 78%). There were 16 (19%) recurrences with 12 being pathology stage 1A. Of these 12 patients, 9 (75%) had CCC of which 2 received adjuvant chemotherapy. Even in the presence of dense adhesions (4.7%), the likelihood of extraovarian disease in CCC and EMCA confined to the ovary was very low. Accordingly, the findings in this study indicate that comprehensive surgical staging for what appears to be stage 1 CCC and EMCA may provide no benefit in detecting occult disease that would upstage the tumor.
Immunohistochemical Analysis of Somatostatin Receptors in Endometriosis Tissue Samples: A Retrospective Study
Authors: Fastrez Maxime , Marchisello Camille , Rassy Marc , Rozenberg Serge , Sirtaine Nicolas
Published: May 2018

Three types of endometriosis are described: superficial peritoneal endometriosis (SPE), ovarian endometrioma (OMA), and deep infiltrating endometriosis (DIE). The expression of somatostatin receptors (SSTR1, 2, and 5) in human endometrial tissue and its ectopic form has been previously studied and may be different in each type of endometriosis. The aim of this study was to assess the immunohistochemical expression of SSTR1, 2, and 5 in tissue samples of SPE, OMA, and DIE. We performed a retrospective analysis in the pathology department database. Patients aged <50 yr and diagnosed with endometriosis have been identified and sorted into 3 groups according to their endometriosis type: SPE, OMA, and DIE. For each selected patient, formalin-fixed paraffin-embedded blocks were retrieved in order to make new sections to be incubated with polyclonal rabbit antibodies anti-SSTR1, 2, and 5. Receptor status was considered as positive on the sections when >50% of the cells showed immunostaining. Seventy-six patients were included in the analysis. SSTR1 and 5 were expressed in 95.4% and 77.2% of SPE, respectively, in 95.8% and 83.3% of OMA, respectively, and in 100% and 80% of DIE, respectively. There was no significant difference between SPE, OMA, and DIE with regard to the SSTR1 (P=0.5) and SSTR5 (P=0.9) expression. We observed a significant difference between SPE (9.0%), OMA (16.6%), and DIE (63.3%) with regard to SSTR2 expression (P<0.05). The present study identifies 2 different immunohistochemical patterns of endometriosis lesions with regard to their SSTR expression: SSTR1+/SSTR2−/SSTR5+ for SPE and OMA, and SSTR1+/SSTR2+/SSTR5+ for DIE.
Augmented Reality–Guided Lumbar Facet Joint Injections
Authors: Agten Christoph A. , Dennler Cyrill , Rosskopf Andrea B. , Jaberg Laurenz , Pfirrmann Christian W.A. , Farshad Mazda
Published: May 2018

Objectives

The aim of this study was to assess feasibility and accuracy of augmented reality–guided lumbar facet joint injections.

Materials and Methods

A spine phantom completely embedded in hardened opaque agar with 3 ring markers was built. A 3-dimensional model of the phantom was uploaded to an augmented reality headset (Microsoft HoloLens). Two radiologists independently performed 20 augmented reality–guided and 20 computed tomography (CT)–guided facet joint injections each: for each augmented reality–guided injection, the hologram was manually aligned with the phantom container using the ring markers. The radiologists targeted the virtual facet joint and tried to place the needle tip in the holographic joint space. Computed tomography was performed after each needle placement to document final needle tip position. Time needed from grabbing the needle to final needle placement was measured for each simulated injection. An independent radiologist rated images of all needle placements in a randomized order blinded to modality (augmented reality vs CT) and performer as perfect, acceptable, incorrect, or unsafe. Accuracy and time to place needles were compared between augmented reality–guided and CT-guided facet joint injections.

Results

In total, 39/40 (97.5%) of augmented reality–guided needle placements were either perfect or acceptable compared with 40/40 (100%) CT-guided needle placements (P = 0.5). One augmented reality–guided injection missed the facet joint space by 2 mm. No unsafe needle placements occurred. Time to final needle placement was substantially faster with augmented reality guidance (mean 14 ± 6 seconds vs 39 ± 15 seconds, P < 0.001 for both readers).

Conclusions

Augmented reality–guided facet joint injections are feasible and accurate without potentially harmful needle placement in an experimental setting.
Falciform Ligament Artery Uptake on 99mTc MAA Planning Scan Before 90Y SIRT Confirmed by Retrospective SPECT/MRI Fusion
Authors: Große Hokamp Nils , Kobe Carsten , O’Donnell James K. , Gupta Amit
Published: May 2018

Selective internal radiation therapy using 90Y spheres is a treatment option for patients with primary or secondary liver cancer. To avoid complications, screening using 99mTc macroaggregated albumin is performed to identify lung shunting and extrahepatic depositions. For the latter, deposition after the anterior abdominal wall is frequently attributed to a patent falciform artery, although the vessel itself is rarely visible on SPECT/CT scans. We demonstrate that retrospective SPECT/MRI fusion clearly attributes the nuclide accumulation to a patent falciform artery. During selective internal radiation therapy, ice packs were placed on the anterior abdominal wall, resulting in a complication-free treatment.
Elongated Appearance of Meckel’s Diverticulum on 99mTcO4 Scintigraphy
Authors: Wu Ha , Zhao Ruifang , Song Zai , Kung B.T. , Zhao Xiaofei
Published: May 2018

A Meckel’s scintigraphy using 99mTcO4 was performed in a 9-year-old boy. The images revealed an elongated abnormal radiotracer accumulation in the right abdomen, which was confirmed as Meckel diverticulum combined with an omphalomesenteric cyst.
Chemokine Receptor CXCR4−Targeted PET/CT With 68Ga-Pentixafor Shows Superiority to 18F-FDG in a Patient With Waldenström Macroglobulinemia
Authors: Luo Yaping , Pan Qingqing , Feng Jun , Cao Xinxin , Li Fang
Published: May 2018

A 69-year-old woman diagnosed with Waldenström macroglobulinemia (WM) was referred for 18F-FDG and 68Ga-Pentixafor PET/CT for evaluation of the disease. Extensive involvement of WM with intense radioactivity in the bone marrow and lymph nodes was found in 68Ga-Pentixafor PET/CT. However, in 18F-FDG PET/CT, the lesions showed significantly lower tracer uptake. Given the superiority of 68Ga-Pentixafor in detecting WM lesions to 18F-FDG in this patient, 68Ga-Pentixafor PET/CT might be a promising imaging modality in assessment of tumor burden of WM in future studies.
Effects of End-Tidal Carbon Dioxide-Guided Fluid Resuscitation on Outcomes in a Cecal Ligation and Puncture Induced Rat Model of Sepsis
Authors: Xu Jing , Zheng Guanghui , Wu Liangliang , Fang Xiangshao , Wang Yue , Jiang Longyuan , Ling Qin , Yang Zhengfei , Tang Wanchun
Published: May 2018

Cecal ligation and puncture (CLP) was used to cause severe sepsis in male Sprague–Dawley rats. There are four groups in this study: sham (n = 5), CLP (n = 10), end-tidal carbon dioxide (ETCO2) (n = 10), and mean arterial pressure (MAP) (n = 10). In ETCO2 group, fluid resuscitation (FR) began when ETCO2 at most 25 mmHg. In MAP group, FR began when MAP at most 100 mmHg. Electrocardiogram, aortic pressure, core temperature, and ETCO2 values were recorded at baseline, 2, 4, 6, 8, 10, and 12 h post-CLP. Lactate level, cardiac output (CO), perfused small vessel density (PSVD), and microvascular flow index (MFI) were assessed at the same time points as above. The results showed that MAP, CO, and ETCO2 gradually decreased after CLP. After FR, MAP, ETCO2, and CO in the ETCO2 group increased compared with the MAP group 12 h after CLP (all P < 0.05). Lactate level remains high in MAP group while decreasing in the ETCO2 group 8 h post-CLP. Both PSVD and MFI deteriorated after CLP in CLP group, though significantly improved in the ETCO2 group 8 h post-CLP. The average survival time in the ETCO2 group was significantly greater than MAP group (14.95 ± 3.90 h vs. 11.15 ± 1.76 h; t = 2.804, P = 0.012). Moreover, ETCO2 showed a negative correlation with lactic acid levels and a positive correlation with CO, PSVD, and MFI. In conclusion, ETCO2 can guide FR implement and improve outcomes of severe sepsis in CLP-inducted rat model. ETCO2 might be a potential index to guiding early FR in severe sepsis.
Oncological and Survival Outcomes in Watch and Wait Patients With a Clinical Complete Response After Neoadjuvant Chemoradiotherapy for Rectal Cancer
Authors: Dattani Mit , Heald Richard J. , Goussous Ghaleb , Broadhurst Jack , São Julião Guilherme P. , Habr-Gama Angelita , Perez Rodrigo Oliva , Moran Brendan J.
Published: May 2018

Objective:

The aim of this study was to evaluate the oncological and survival outcomes of a Watch and Wait policy in rectal cancer after a clinical complete response (cCR) following neoadjuvant chemoradiotherapy.

Background:

The detection of a cCR after neoadjuvant treatment may facilitate a nonoperative approach in selected patients. However, the long-term safety of this strategy remains to be validated.

Method:

This is a systematic review of the literature to determine the oncological outcomes in Watch and Wait patients. The primary outcome was the cumulative rate of local regrowth, success of salvage surgery, and incidence of metastases. We also evaluated survival outcomes. A pooled analysis of manually extracted summary statistics from individual studies was carried out using inverse variance weighting.

Results:

Seventeen studies comprising 692 patients were identified; incidence of cCR was 22.4% [95% confidence interval (CI),14.3–31.8]. There were 153 (22.1%) local regrowths, of which 96% (n = 147/153) manifested in the first 3 years of surveillance. The 3-year cumulative risk of local regrowth was 21.6% (95% CI, 16.0–27.8). Salvage surgery was performed in 88% of patients, of which 121 (93%) had a complete (R0) resection. Fifty-seven metastases (8.2%) were detected, and 35 (60%) were isolated without evidence of synchronous regrowths; 3-year incidence was 6.8% (95% CI, 4.1–10.2). The 3-year overall survival was 93.5% (95% CI, 90.2–96.2).

Conclusion:

In rectal cancer patients with a cCR following neoadjuvant chemoradiotherapy, a Watch and Wait policy appears feasible and safe. Robust surveillance with early detection of regrowths allows a high rate of successful salvage surgery, without an increase in the risk of systemic disease, or adverse survival outcomes.
MRI of non-Alzheimer's dementia: current and emerging knowledge
Authors: Filippi Massimo , Agosta Federica
Published: May 2018

Purpose of review

The correct classification of non-Alzheimer's dementia is crucial to study disease mechanisms, predict disease progression and test disease-specific treatments. Brain atrophy assessment with morphometric MRI is currently the gold standard for in-vivo localization of neurodegeneration. Structural and functional connectivity biomarkers are becoming increasingly available. This review emphasizes the potential applications of MRI in the main non-Alzheimer's dementia such as dementia with Lewy bodies (DLB) and frontotemporal dementia (FTD).

Recent findings

MRI can predict co-occurrence of Alzheimer's disease pathology in DLB patients and pathological subtypes in patients with FTD. Innovative applications of brain connectivity are providing neural substrates explaining the network-dependent spread of pathology in non-Alzheimer's dementia. Advanced MRI can be relevant in characterizing the temporal sequence of the earliest functional and structural brain changes in individuals at risk for neurodegenerative non-Alzheimer's diseases.

Morphometric MRI is clinically applied at an individual level for the differentiation between Alzheimer's and non-Alzheimer's dementia and may help in predicting underlying pathology, which will be critical for the success of disease-modifying therapies. Longitudinal, multimodal MRI studies are required to demonstrate whether advanced magnetic resonance techniques can be reliable outcome measures to monitor disease progression in clinical trials, starting from the presymptomatic stage.
Loss of glutathione redox homeostasis impairs proteostasis by inhibiting autophagy-dependent protein degradation
Authors: Guerrero-Gómez David , Mora-Lorca José Antonio , Sáenz-Narciso Beatriz , Naranjo-Galindo Francisco José , Muñoz-Lobato Fernando , Parrado-Fernández Cristina , Cedazo-Minguez Ángel , Link Christopher D. , Neri Christian , Sequedo María Dolores , Vázquez-Manrique Rafael P. , Fernández-Suárez Elena , Goder Veit , Pané Roser , Cabiscol Elisa , Askjaer Peter , Cabello Juan , Miranda-Vizuete Antonio
Published: May 2018

In the presence of aggregation-prone proteins, the cytosol and endoplasmic reticulum (ER) undergo a dramatic shift in their respective redox status, with the cytosol becoming more oxidized and the ER more reducing. However, whether and how changes in the cellular redox status may affect protein aggregation is unknown. Here, we show that C. elegans mutants lacking glutathione reductase gsr-1 gene enhance the deleterious phenotypes of heterologous human as well as endogenous worm aggregation-prone proteins. These effects are phenocopied by the GSH depleting agent diethyl maleate. Additionally, gsr-1 mutants abolish the nuclear translocation of HLH-30/TFEB transcription factor, a key inducer of autophagy, and strongly impair the degradation of the autophagy substrate p62/SQST-1::GFP, revealing glutathione reductase may have a role in the clearance of protein aggregates by autophagy. Blocking autophagy in gsr-1 worms expressing aggregation-prone proteins results in strong synthetic developmental phenotypes and lethality, supporting the physiological importance of glutathione reductase in the regulation of misfolded protein clearance. Furthermore, impairing redox homeostasis in both yeast and mammalian cells induces toxicity phenotypes associated with protein aggregation. Together, our data reveal that glutathione redox homeostasis may be central to proteostasis maintenance through autophagy regulation.
Rapid sex-specific evolution of age at maturity is shaped by genetic architecture in Atlantic salmon
Authors: Czorlich Y. , Aykanat T. , Erkinaro J. , Orell P. , Primmer CR.
Published: May 2018

Understanding the mechanisms by which populations adapt to their environments is a fundamental aim in biology. However, it remains challenging to identify the genetic basis of traits, provide evidence of genetic changes and quantify phenotypic responses. Age at maturity in Atlantic salmon represents an ideal trait to study contemporary adaptive evolution as it has been associated with a single locus in thevgll3region, and has also strongly changed in recent decades. Here, we provide an empirical example of contemporary adaptive evolution of a large effect locus driving contrasting sex-specific evolutionary responses at the phenotypic level. We identified an 18% decrease in thevgll3allele associated with late maturity (L) in a large and diverse salmon population over 36 years, induced by sex-specific selection during the sea migration. Those genetic changes resulted in a significant evolutionary response in males only, due to sex-specific dominance patterns andvgll3allelic effects. Thevgll3allelic and dominance effects differed greatly in a second population and were likely to generate different selection and evolutionary patterns. Our study highlights the importance of knowledge of genetic architecture to better understand fitness trait evolution and phenotypic diversity. It also emphasizes the potential role of adaptive evolution in the trend toward earlier maturation observed in numerous Atlantic salmon populations worldwide.
Comparison of the 3-D patterns of the parasympathetic nervous system in the lung at late developmental stages between mouse and chicken
Authors: Watanabe Tadayoshi , Nakamura Ryo , Takase Yuta , Susaki Etsuo A , Ueda Hiroki R , Tadokoro Ryosuke , Takahashi Yoshiko
Published: May 2018

Although the basic schema of the body plan is similar among different species of amniotes (mammals, birds, and reptiles), the lung is an exception. Here, anatomy and physiology are considerably different, particularly between mammals and birds. In mammals, inhaled and exhaled airs mix in the airways, whereas in birds the inspired air flows unidirectionally without mixing with the expired air. This bird-specific respiration system is enabled by the complex tubular structures called parabronchi where gas exchange takes place, and also by the bellow-like air sacs appended to the main part of the lung. That the lung is predominantly governed by the parasympathetic nervous system has been shown mostly by physiological studies in mammals. However, how the parasympathetic nervous system in the lung is established during late development has largely been unexplored both in mammals and birds. In this study, by combining immunocytochemistry, the tissue-clearing CUBIC method, and ink-injection to airways, we have visualized the 3-D distribution patterns of parasympathetic nerves and ganglia in the lung at late developmental stages of mice and chickens. These patterns were further compared between these species, and three prominent similarities emerged: (1) parasympathetic postganglionic fibers and ganglia are widely distributed in the lung covering the proximal and distal portions, (2) the gas exchange units, alveoli in mice and parabronchi in chickens, are devoid of parasympathetic nerves, (3) parasympathetic nerves are in close association with smooth muscle cells, particularly at the base of the gas exchange units. These observations suggest that despite gross differences in anatomy, the basic mechanisms underlying parasympathetic control of smooth muscles and gas exchange might be conserved between mammals and birds.
Effects of Parkinson’s disease and dopamine on digit span measures of working memory
Authors: Grogan John Patrick , Knight Lisa Emily , Smith Laura , Irigoras Izagirre Nerea , Howat Alexandra , Knight Brogan Elizabeth , Bickerton Anastasia , Isotalus Hanna Kristiina , Coulthard Elizabeth Jane
Published: May 2018

Rationale

Parkinson’s disease (PD) impairs working memory (WM) - the ability to maintain items in memory for short periods of time and manipulate them. There is conflicting evidence on the nature of the deficits caused by the disease, and the potential beneficial and detrimental effects of dopaminergic medication on different WM processes.

Objectives

We hypothesised that PD impairs both maintenance and manipulation of items in WM and dopaminergic medications improve this in PD patients but impair it in healthy older adults.

Methods

We tested 68 PD patients ON and OFF their dopaminergic medication, 83 healthy age-matched controls, and 30 healthy older adults after placebo and levodopa administration. We used the digit span, a WM test with three components (forwards, backwards and sequence recall) that differ in the amount of manipulation required. We analysed the maximum spans and the percentage of lists correctly recalled, which probe capacity of WM and the accuracy of the memory processes within this capacity, respectively.

Results

PD patients had lower WM capacity across all three digit span components, but only showed reduced percentage accuracy on the components requiring manipulation (backwards and sequence spans). Dopaminergic medication did not affect performance in PD patients. In healthy older adults, levodopa did not affect capacity, but did impair accuracy on one of the manipulation components (sequence), without affecting the other (backwards).

Conclusions

This suggests a non-dopaminergic deficit of maintenance capacity and manipulation accuracy in PD patients, and a potential “overdosing” of intact manipulation mechanisms in healthy older adults by levodopa.
Inhibitory and excitatory mechanisms in the human cingulate-cortex support reinforcement learning
Authors: Bezalel Vered , Paz Rony , Tal Assaf
Published: May 2018

The dorsal anterior cingulate cortex (dACC) is crucial for motivation, reward- and error-guided decision-making, yet its excitatory and inhibitory mechanisms remain poorly explored in humans. In particular, the balance between excitation and inhibition (E/I), demonstrated to play a role in animal studies, is difficult to measure in behaving humans. Here, we used magnetic-resonance-spectroscopy (1H-MRS) to examine these mechanisms during reinforcement learning with three different conditions: high cognitive load (uncertainty); probabilistic discrimination learning; and a control null-condition. Subjects learned to prefer the gain option in the discrimination phase and had no preference in the other conditions. We found increased GABA levels during the uncertainty condition, suggesting recruitment of inhibitory systems during high cognitive load when trying to learn. Further, higher GABA levels during the null (baseline) condition correlated with improved discrimination learning. Finally, excitatory and inhibitory levels were correlated during high cognitive load. The result suggests that availability of dACC inhibitory resources enables successful learning. Our approach establishes a novel way to examine the contribution of the balance between excitation and inhibition to learning and motivation in behaving humans.
Testing Darwin’s hypothesis about the most wonderful plant in the world: The Venus flytrap’s marginal spikes are a ‘horrid prison’ for moderate-sized insect prey
Authors: Davis Alexander L. , Babb Matthew H. , Lee Brandon T. , Martin Christopher H.
Published: May 2018

Botanical carnivory is a novel feeding strategy associated with numerous physiological and morphological adaptations. However, the benefits of these novel carnivorous traits are rarely tested. Here, we used field observations and lab experiments to test the prey capture function of the marginal spikes on snap traps of the Venus flytrap (Dionaea muscipula). Our field and laboratory results suggested surprisingly inefficient capture success: fewer than 1 in 4 prey encounters led to prey capture. Removing the marginal spikes decreased the rate of prey capture success for moderate-sized cricket prey by 90%, but this effect disappeared for larger prey. The nonlinear benefit of spikes suggests that they provide a better cage for capturing more abundant insects of moderate and small sizes, but may also provide a foothold for rare large prey to escape. Our observations support Darwin’s hypothesis that the marginal spikes form a ‘horrid prison’ that increases prey capture success for moderate-sized prey, but the decreasing benefit for larger prey is unexpected and previously undocumented. Thus, we find surprising complexity in the adaptive landscape for one of the most wonderful evolutionary innovations among all plants. These findings further enrich our understanding of the evolution and diversification of novel trap morphology in carnivorous plants.
Neural plasticity following surgical correction of strabismus in monkeys
Authors: Pullela Mythri , Ağaoğlu Mehmet N. , Joshi Anand C. , Ağaoğlu Sevda , Coats David K. , Das Vallabh E.
Published: May 2018

The preferred treatment for correcting strabismus in humans involves the surgical manipulation of extraocular muscles (EOM). Although widely practiced, this treatment has varying levels of success and permanence, possibly due to adaptive responses within the brain or at the muscle. We investigated neural plasticity following strabismus surgery by recording responses from cells in the oculomotor and abducens nuclei before and after two monkeys with exotropia (divergent strabismus) underwent a strabismus correction surgery that involved weakening of the lateral rectus (LR) and strengthening of the medial rectus (MR) muscle of one eye. Eye movement and neuronal data were collected for a period of 6-10 months after surgery during a monocular viewing smooth-pursuit task. These data were fit with a first-order equation and resulting coefficients were used to estimate the population neuronal drive (ND) to each EOM of the viewing and deviated eyes. Surgery resulted in an~70% reduction in strabismus angle in both animals that reverted towards pre-surgical misalignment by about 6 months after treatment. In the first month after surgery, the ND to the treated MR reduced in one animal and ND to the LR increased in the other animal, both indicating active neural plasticity that reduced the effectiveness of the treatment. Although these neuronal drive changes resolved by 6 months, we also found evidence for an inappropriate peripheral muscle adaptation that limited the effectiveness of surgery over the long term. Outcome of strabismus correction surgery could be improved by identifying ways to enhance ‘positive’ adaptation and limit ‘negative’ adaptation.

Significance statement

This is the first study of its kind to longitudinally follow behavioral and neural responses before and after a typical strabismus correction surgery in a monkey model for strabismus. We show the nature of muscle and neuronal plasticity that follows strabismus correction surgery.
MiR-29b-1-5p is altered in BRCA1 mutant tumours and is a biomarker in basal-like breast cancer
Authors: Milevskiy Michael J.G. , Sandhu Gurveen K. , Wronski Anna , Korbie Darren , Brewster Brooke L. , Shewan Annette , Edwards Stacey L. , French Juliet D. , Brown Melissa A.
Published: May 2018

Depletion of BRCA1 protein in mouse mammary glands results in defects in lactational development and increased susceptibility to mammary cancer. Extensive work has focussed on the role of BRCA1 in the normal breast and in the development of breast cancer, the cell of origin for BRCA1 tumours and the protein-coding genes altered in BRCA1 deficient cells. However, the role of non-coding RNAs in BRCA1-deficient cells is poorly understood. To evaluate miRNA expression in BRCA1 deficient mammary cells, RNA sequencing was performed on the mammary glands of Brca1 knockout mice. We identified 140 differentially expressed miRNAs, 9 of which were also differentially expressed in human BRCA1 breast tumours or familial non-BRCA1 patients and during normal gland development. We show that BRCA1 binds to putativecis-elements in promoter regions of the miRNAs and regulates their expression, and that four miRNAs (miR-29b-1-5p, miR-664, miR-16-2 and miR-744) significantly stratified the overall survival of basal-like tumours. Importantly the prognostic value of miR-29b-1-5p was higher in significance than several commonly used clinical biomarkers. These results emphasize the role of Brca1 in modulating expression of miRNAs and highlights the potential for BRCA1 regulated miRNAs to be informative biomarkers associated with BRCA1 loss and survival in breast cancer.