bluuebunny/crossref_metadata_2025 huggingface dataset:
A Novel Derivation Predicting Survival After Primary Tumor Resection in Stage IV Colorectal Cancer: Validation of a Prognostic Scoring Model and an Online Calculator to Provide Individualized Survival Estimation
Authors: Tan Winson Jianhong , Dorajoo Sreemanee Raaj , Chee Madeline Yen Min , Tan Wah Siew , Foo Fung Joon , Tang Choong Leong , Chew Min Hoe
Published: August 2017

BACKGROUND:

A prognostic scoring model has been devised previously to predict survival following primary tumor resection in patients with metastatic colorectal cancer and unresectable metastases. This has yet to be validated.

OBJECTIVE:

The main objectives of this study are to validate the proposed prognostic scoring model and create an interactive online calculator to estimate an individual’s survival after primary tumor resection.

DESIGN:

Clinical data and survival outcomes of patients were extracted from a prospectively maintained database. Patients were categorized into good, moderate, or poor survivor groups based on the previously proposed scoring algorithm. Discrimination was assessed and recalibration was performed, with the recalibrated model implemented as an interactive Web application to provide individualized survival probability.

SETTINGS:

This study was conducted at a tertiary referral center.

PATIENTS:

The study included 324 consecutive patients with metastatic colorectal carcinoma and unresectable metastases who underwent primary tumor resection between January 2008 and December 2013.

MAIN OUTCOME MEASURES:

The primary outcome measured was overall survival.

RESULTS:

Three hundred twenty-four patients were included in the study. Median survival in the good, moderate, and poor prognostic groups was 56.8, 25.7, and 19.9 months (log rank test, p = 0.003). The κ statistic was 0.638 and R
2

D
was 0.101. Significant differences in survival were found between the moderate and good prognostic groups (HR, 2.79; 95% CI, 1.51–5.15; p = 0.001) and between poor and good prognostic groups (HR, 4.12; 95% CI, 1.98–8.55; p < 0.001). The model was implemented as an interactive online calculator to provide individualized survival estimation after primary tumor resection (http://bit.ly/Stage4PrognosticScore).

LIMITATIONS:

Selection bias and single-center data preclude the generalizability of the proposed model. Information regarding the severity or likelihood of developing symptoms from the primary tumor were also not accounted for in the prognostic scoring model proposed.

CONCLUSIONS:

The prognostic scoring model provides good prognostic stratification of survival after primary tumor resection and may be a useful tool to predict survival after primary tumor resection. See Video Abstract at http://links.lww.com/DCR/A330.
Laparoscopic Versus Open Lateral Lymph Node Dissection for Locally Advanced Low Rectal Cancer: A Subgroup Analysis of a Large Multicenter Cohort Study in Japan
Authors: Yamaguchi Tomohiro , Konishi Tsuyoshi , Kinugasa Yusuke , Yamamoto Seiichiro , Akiyoshi Takashi , Okamura Ryosuke , Ito Masaaki , Nishimura Yoji , Shiozawa Manabu , Yamaguchi Shigeki , Hida Koya , Sakai Yoshiharu , Watanabe Masahiko
Published: August 2017

BACKGROUND:

Mesorectal excision with lateral lymph node dissection is the standard treatment for locally advanced low rectal cancer in Japan. However, the safety and feasibility of laparoscopic lateral lymph node dissection remain to be determined.

OBJECTIVE:

The purpose of this study was to evaluate the safety and feasibility of laparoscopic versus open lateral lymph node dissection for locally advanced low rectal cancer.

DESIGN:

This was a retrospective cohort study using an exact matching method.

SETTING:

We conducted a multicenter study of 69 specialized centers in Japan.

PATIENTS:

Patients with consecutive midrectal or low rectal adenocarcinoma cancer stage II to III who underwent mesorectal excision with curative intent between 2010 and 2011 were recruited.

MAIN OUTCOME MEASURES:

Short-term and oncological outcomes were compared between the laparoscopic and open-surgery groups.

RESULTS:

Of the 1500 eligible patients, 676 patients who underwent lateral lymph node dissection were analyzed, including 137 patients who were treated laparoscopically and 539 patients who were treated with open surgery. After matching, the patients were stratified into laparoscopic (n = 118) and open-surgery (n = 118) groups. Operative times in the overall cohort were significantly longer (461 vs 372 min) in the laparoscopic versus the open-surgery group. In the laparoscopic group, the blood loss volume was significantly smaller (193 vs 722 mL), with fewer instances of blood transfusion (7.3% vs 25.5%) compared with the open-surgery group. The postoperative complication rates were 35.8% and 43.6% for the laparoscopic and open-surgery groups (p = 0.10). The 3-year relapse-free survival rates were 80.3% and 72.6% for the laparoscopic and open-surgery groups (p = 0.07).

LIMITATIONS:

The study was limited by its retrospective design and potential selection bias.

CONCLUSIONS:

Laparoscopic lateral lymph node dissection is safe and feasible for cancer stage II to III low rectal cancer and is associated with similar oncological outcomes as open lateral lymph node dissection. See Video Abstract at http://links.lww.com/DCR/A334.
Postoperative Chemoradiotherapy After Local Resection for High-Risk T1 to T2 Low Rectal Cancer: Results of a Single-Arm, Multi-Institutional, Phase II Clinical Trial
Authors: Sasaki Takeshi , Ito Yoshinori , Ohue Masayuki , Kanemitsu Yukihide , Kobatake Takaya , Ito Masaaki , Moriya Yoshihiro , Saito Norio
Published: August 2017

BACKGROUND:

After treatment with local excision for TNM stage I low rectal cancer, the risk of local recurrence is not only high for T2 lesions but also for T1 lesions with features of massive invasion to the submucosal layer and/or lymphovascular invasion.

OBJECTIVE:

The purpose of this study was to determine the efficacy of chemoradiotherapy combined with local excision in the treatment of T1 to T2 low rectal cancer.

DESIGN:

We conducted a prospective, single-arm, phase II trial.

SETTINGS:

This was a multicenter study.

PATIENTS:

From April 2003 to October 2010, 57 patients were treated with local excision after additional external beam irradiation (45 Gy) plus continuous 5-week intravenous injection of 5-fluorouracil (250 mg/m2 per day) at 10 domestic hospitals. Fifty-three patients had clinical T1N0 lesions, and 4 had T2N0 lesions in the low rectum, located below the peritoneal reflection.

MAIN OUTCOMES MEASURES:

The primary end point was disease-free survival at 5 years.

RESULTS:

The completion rate for full-dose chemoradiotherapy was 86% (49/57). Serious, nontransient treatment-related complications were not reported. With a median follow-up of 7.3 years after local excision, the 5-year disease-free survival rate was 94% for the 53 patients with T1 lesions and 75% for the 4 patients with T2 lesions. There were 2 local recurrences during the entire observation period. Anal function after local excision and chemoradiation were kept at almost the same levels as observed before treatment.

LIMITATIONS:

The study was limited by the small number of registered T2 rectal cancers, retrospective evaluations of quality of life, and the exclusion of poorly differentiated adenocarcinoma (a high-risk feature of T1 lesions).

CONCLUSIONS:

The addition of chemoradiotherapy to local excision of T1 rectal adenocarcinomas with poor prognostic features including deep submucosal invasion and lymphovascular invasion could improve on less favorable historic oncologic outcomes of local excision alone in this high-risk group for lymph node metastasis. See Video Abstract at http://links.lww.com/DCR/A421.
Is the Failure of Laparoscopic Peritoneal Lavage Predictable in Hinchey III Diverticulitis Management?
Authors: Greilsamer Tristan , Abet Emeric , Meurette Guillaume , Comy Michel , Hamy Antoine , Lehur Paul-Antoine , Venara Aurélien , Duchalais Emilie
Published: August 2017

BACKGROUND:

Laparoscopic peritoneal lavage is an alternative to sigmoid resection in Hinchey III diverticulitis (generalized purulent peritonitis). The main limitation of laparoscopic peritoneal lavage is the higher rate of reoperation for persistent sepsis in comparison with sigmoid resection.

OBJECTIVE:

The purpose of the current study was to identify risk factors for laparoscopic peritoneal lavage failure in patients who have Hinchey III diverticulitis.

DESIGN:

This was a retrospective multicenter study.

SETTINGS:

The study was conducted in 3 clinical sites in France.

PATIENTS:

From 2006 to 2015, all consecutive patients undergoing emergent surgery for diverticulitis were reviewed. All patients operated on with laparoscopic peritoneal lavage for laparoscopically confirmed Hinchey III diverticulitis were included.

MAIN OUTCOME MEASURES:

The main outcome was laparoscopic peritoneal lavage failure, defined as reoperation or death at 30 postoperative days.

RESULTS:

A series of 71 patients (43 men, mean age 58 ± 15 years) were operated on with laparoscopic peritoneal lavage for Hinchey III diverticulitis. Laparoscopic peritoneal lavage failed in 14 (20%) of them: 1 died and 13 underwent reoperations. No major complication (Dindo-Clavien score ≥3) occurred after reoperation. Immunosuppressive drugs (p = 0.01) and ASA grade ≥3 (p = 0.02) were associated with laparoscopic peritoneal lavage failure after univariate analysis. Multivariate analysis identified only immunosuppressive drug intake (steroids or chemotherapy for cancer) as an independent predictive factor. Mean length of stay was 14.9 days (5–67). At the end of the 30 first postoperative days, 12 (17%) patients had a stoma.

LIMITATIONS:

The study was limited by its retrospective nature and the small size of the cohort.

CONCLUSION:

Our results highlight immunosuppressive drug intake as a major risk factor for laparoscopic peritoneal lavage failure in patients who have Hinchey III diverticulitis. Immunosuppression and severe comorbidities (ASA ≥3) should be considered when selecting a surgical option in patients with Hinchey III diverticulitis. See Video Abstract at http://links.lww.com/DCR/A423.
Is MRI of the Liver Needed During Routine Preoperative Workup for Colorectal Cancer?
Authors: Kang Sung Il , Kim Duck-Woo , Cho Jai Young , Park Jihoon , Lee Kyung Ho , Son Il Tae , Oh Heung-Kwon , Kang Sung-Bum
Published: August 2017

BACKGROUND:

The clinical efficacy of gadoxetic acid–enhanced liver MRI as a routine preoperative procedure for all patients with colorectal cancer remains unclear.

OBJECTIVE:

The purpose of this study was to evaluate the efficacy of preoperative gadoxetic acid–enhanced liver MRI for the diagnosis of liver metastasis in patients with colorectal cancer.

DESIGN:

This was a retrospective analysis from a prospective cohort database.

SETTINGS:

All of the patients were from a subspecialty practice at a tertiary referral hospital.

PATIENTS:

Patients who received preoperative gadoxetic acid–enhanced liver MRI after CT and attempted curative surgery for colorectal cancer were included.

MAIN OUTCOME MEASURES:

The number of equivocal hepatic lesions based on CT and gadoxetic acid–enhanced liver MRI and diagnostic use of the gadoxetic acid–enhanced liver MRI were measured.

RESULTS:

We reviewed the records of 690 patients with colorectal cancer. Equivocal hepatic lesions were present in 17.2% of patients based on CT and in 4.5% based on gadoxetic acid–enhanced liver MRI. Among 496 patients with no liver metastasis based on CT, gadoxetic acid–enhanced liver MRI detected equivocal lesions in 15 patients and metastasis in 3 patients. Among 119 patients who had equivocal liver lesions on CT, gadoxetic acid–enhanced liver MRI indicated hepatic lesions in 103 patients (86.6%), including 90 with no metastasis and 13 with metastasis. Among 75 patients who had liver metastasis on CT, gadoxetic acid–enhanced liver MRI indicated that the hepatic lesions in 2 patients were benign, in contrast to CT findings. The initial surgical plans for hepatic lesions according to CT were changed in 17 patients (3%) after gadoxetic acid–enhanced liver MRI.

LIMITATIONS:

This study was limited by its retrospective design.

CONCLUSIONS:

The clinical efficacy of gadoxetic acid–enhanced liver MRI as a routine preoperative procedure for all patients with colorectal cancer is low, in spite of its high diagnostic value for detecting liver metastasis. However, this study showed gadoxetic acid–enhanced liver MRI was helpful in characterizing equivocal hepatic lesions identified in CT and could lead to change in treatment plans for some patients. See Video Abstract at http://links.lww.com/DCR/A420.
SIGNIFICANT REDUCTION OF BOTH PERIPAPILLARY AND SUBFOVEAL CHOROIDAL THICKNESS AFTER PANRETINAL PHOTOCOAGULATION IN PATIENTS WITH TYPE 2 DIABETES
Authors: Kang Hae Min , Lee Na Eun , Choi Jeong Hoon , Koh Hyoung Jun , Lee Sung Chul
Published: August 2017

Purpose:

To evaluate changes in peripapillary choroidal thickness (PCT) and subfoveal choroidal thickness (SFCT) after panretinal photocoagulation (PRP) for diabetic retinopathy.

Methods:

This retrospective interventional study included 59 treatment-naive eyes of 33 patients who underwent PRP and completed ≥12 months of follow-up. Peripapillary choroidal thickness and SFCT were measured at baseline and 1, 3, 6, and 12 months post-PRP. Differences between baseline and 12 months (ΔSFCT and ΔPCT) and percentage changes (ΔSFCT or ΔPCT/baseline × 100%) were determined.

Results:

Mean SFCT was 287.7 ± 76.7 μm (139.0–469.0 μm) at baseline and 225.8 ± 62.0 μm (102.5–379.5 μm) 12 months post-PRP (P < 0.001). Mean PCT was 161.2 ± 16.5 μm (75.3–308.1 μm) at baseline and 128.4 ± 41.8 μm (73.0–212.9 μm) 12 months post-PRP (P < 0.001). ΔSFCT was −61.3 ± 28.7 μm (−139.5 to −17.0 μm), and %SFCT was 21.2 ± 7.2% (6.8% to 36.1%). ΔPCT was −36.4 ± 23.2 μm (−149.1 to 5.4 μm), and %PCT was 22.4 ± 12.0% (2.5% to 62.6%). Diabetic retinopathy severity was the only factor significantly correlated with %SFCT (β = 0.500, P = 0.004) and %PCT (β = 0.152, P = 0.024).

Conclusion:

Both PCT and SFCT reduced significantly after PRP. Diabetic retinopathy severity was significantly correlated with post-PRP changes of peripapillary and SFCT.
Pain and itch outcome trajectories differ among European American and African American survivors of major thermal burn injury
Authors: Mauck Matthew C. , Smith Jennifer , Shupp Jeffrey W. , Weaver Mark A. , Liu Andrea , Bortsov Andrey V. , Lateef Bilal , Jones Samuel W. , Williams Felicia , Hwang James , Karlnoski Rachel , Smith David J. , Cairns Bruce A. , McLean Samuel A.
Published: August 2017

More than half of individuals experiencing major thermal burn injury (MThBI) receive an autologous skin graft (autograft), in which skin is removed from a healthy “donor” site and transplanted to the burn site. Persistent pain and itch at the graft site are major causes of suffering and disability in MThBI survivors. African Americans have a higher risk of MThBI, and in other clinical settings African Americans experience a greater burden of pain and itch relative to European Americans. However, to our knowledge, ethnic differences in skin graft site pain and itch outcomes after MThBI have not been assessed. We evaluated skin graft site pain and itch severity (0-10 Numeric Rating Scale [NRS]) over 1 year in a prospective multicenter cohort sample of African Americans and European Americans. In adjusted linear mixed models, African Americans experienced a slower rate of pain resolution in the acute phase of recovery (β = −0.05 vs −0.08 NRS points per day, P < 0.001), which resulted in a higher pain severity in the persistent phase of recovery (NRS mean difference = 1.21, 95% confidence interval [0.12-2.29]), although not statistically significant after correction for multiple comparisons. African Americans also experience greater itch severity in 6 weeks to 12 months after burn injury compared with European Americans (NRS mean difference = 1.86 [0.80-2.93]), which results from a faster rate of itch development in African Americans in the acute recovery phase after burn injury. Future studies may improve outcomes in African Americans and lead to new pathogenic insights that benefit all burn injury survivors.
Anatomical Relationship of the Middle Cranial Fossa Dura to Surface Landmarks of the Temporal Bone
Authors: Alhussaini Mohamed A. , Mattingly Jameson K. , Cass Stephen P.
Published: August 2017

Hypothesis:

The suprameatal crest and temporal line provides a reliable landmark to the middle fossa dura.

Background:

Surface anatomy of the temporal bone is used to guide mastoid surgery, but studies investigating these landmarks are limited. The aim of this study was to examine the anatomical relationship of the middle fossa dura to the temporal line.

Methods:

Thirty-two fresh hemicephalic temporal bones were prepared by drawing four lines along the mastoid including the suprameatal crest and temporal line (line 2), one line 5 mm superior to line 2 (line 1), and one 5 mm inferior to line 2 (line 3), and at Reid's base line (line 4). Four points were marked along these lines anterior to posterior 3 mm apart. A 1 mm bur was used to drill perpendicular to these points to examine the relationship to the middle fossa dura.

Results:

The dura was found inferior to line 2 in 6.3% at point 1, 6.3% at point 2, 9.4% at point 3, and 18.8% at point 4. The dura in line 1 was found inferior to point 1 in 52.1%, point 2 in 46.9%, point 3 in 56.3%, and point 4 in 62.5%. Only one specimen (3.1%) had dura lying inferior to line 3. No specimens were inferior line 4 at any point.

Conclusion:

The dura of the middle fossa lies superior the temporal line in >80% of specimens and at least 5 mm superior in nearly half. This indicates the temporal line or a line slightly inferior to this is reliably inferior the middle fossa dura.
Surgery With or Without Postoperative Radiation Therapy for Early-stage External Auditory Canal Squamous Cell Carcinoma: A Meta-analysis
Authors: Oya Ryohei , Takenaka Yukinori , Takemura Kazuya , Ashida Naoki , Shimizu Kotaro , Kitamura Takahiro , Yamamoto Yoshifumi , Uno Atsuhiko
Published: August 2017

Objective:

External auditory canal squamous cell carcinoma (EACSCC) is a rare disease with no standard treatment supported by high-level evidence. The aim of this study was to investigate EACSCC prognoses according to treatment modality and thus determine the optimal intervention for early-stage disease.

Data Sources:

PubMed, Scopus, and Ichushi-Web searches of the English and Japanese-language literature published between January 1, 2006 and December 31, 2016 were performed using the key words “external auditory canal cancer” and “temporal bone cancer.”

Study Selection:

Articles related to EACSCC that include the 5-year overall survival rate or individual patient data for histological types, follow-up periods, and final outcomes were enrolled.

Data Extraction:

Sex, age, Moody's modified Pittsburgh stage, type of treatment modality, type of operation, follow-up period, and 5-year survival rates were extracted.

Data Synthesis:

Twenty articles were used for the aggregate meta-analysis using a random-effects model, and 18 articles that reported 99 patients with early-stage EACSCC were used for the individual patient data meta-analysis.

Conclusion:

The 5-year overall survival rate of early-stage EACSCC was 77%. Postoperative radiation therapy (PORT) was performed in 45% of stage I patients and 68% of stage II patients. Survival analysis of all patients showed no differences between the surgery-only and PORT groups; however, PORT exhibited a better prognosis than surgery alone among patients with stage I disease (p = 0.003, log-rank test). This result indicated that PORT can be the standard therapy for stages I and II EACSCC.
The First Reported Case of Primary Intestinal-type Adenocarcinoma of the Middle Ear and Review of the Literature
Authors: Nader Marc-Elie , Bell Diana , Ginsberg Lawrence , DeMonte Franco , Gunn G. Brandon , Gidley Paul W.
Published: August 2017

Objective:

Adenocarcinoma of the middle ear is a rare entity that must be distinguished from other adenomatous tumors of the temporal bone. We present the first patient of an intestinal-type adenocarcinoma originating from the middle ear.

Patients:

A 58-year-old woman presented with an 8-year history of left otorrhea. Her middle ear effusions were quite thick and gummy. She underwent eight sets of pressure-equalization tubes within 3 years. In 2011, her physical examination identified a middle ear mass, and she underwent mastoidectomy. A middle ear adenoma was resected. She underwent an additional three mastoidectomies for recurrence, with pathology from the 4th mastoidectomy revealing a diagnosis of adenocarcinoma. Imaging, at that time, showed an extensive temporal bone and Eustachian tube tumor.

Interventions:

She underwent a left subtotal temporal bone resection, parotidectomy, infratemporal fossa resection, dural resection, and microvascular free flap reconstruction followed by postoperative proton beam radiotherapy.

Main Outcome Measures:

The final pathology report revealed intestinal-type adenocarcinoma.

Results:

Treatment was successful and the patient remains disease free 4 years later.

Conclusion:

This is the first report of an intestinal-type adenocarcinoma of the middle ear and temporal bone. This patient also illustrates the difficulty of accurate histologic diagnosis of adenomatous tumors of the middle ear.
Patulous Eustachian Tube Dysfunction: Patient Demographics and Comorbidities
Authors: Ward Bryan K. , Ashry Yehia , Poe Dennis S.
Published: August 2017

Objective:

The objective is to describe a large cohort of patients presenting with patulous Eustachian tube (pET) dysfunction.

Study Design:

Retrospective patient series.

Setting:

Tertiary referral center.

Patients:

All outpatient visits (2004–2016) that were assigned ICD9 code (381.7-Patulous Eustachian tube) were screened. Only patients with observed tympanic membrane movements during ipsilateral nasal breathing or acoustic reflex decay testing demonstrating transmitted nasal breathing were included (n = 190, n = 239 ears).

Main Outcome Measures:

Demographics and nasopharyngoscopy/otomicroscopy findings by comorbidities.

Results:

The majority (54%) was female and mean age of symptom onset was 38.0 (SD 20.0) years. Common symptoms included voice autophony (93%), breath autophony (92%), aural fullness (57%), pulsatile tinnitus (17%), and crackling or rumbling sounds (14%). Symptoms increased in frequency and duration with time (65%), were exacerbated with exercise (27%), and improved with placing the head in a dependent position (65%), sniffing (28%), upper respiratory infection (8%), and ipsilateral internal jugular vein compression (12%). In 52% pET was bilateral. Common comorbidities include environmental allergy (49%), weight loss (35%), laryngopharyngeal reflux (33%), anxiety (31%), autoimmunity (13%), and neuromuscular disease (8%). Allergy and anxiety patients were younger and more likely to have tonic contraction of the tensor veli palatini on exam (p < 0.05, χ
2). Allergy patients also had relief with sniffing and tympanic membrane retraction (p < 0.01, χ
2). Weight loss patients reported mean loss of 19.7 kg (SD 23.1), and were older, more rapidly diagnosed, and more likely to have persistent symptoms (p < 0.05). Initially, all patients were treated medically, with 47% eventually electing surgical intervention.

Conclusion:

pET is progressive, often bilateral, and possibly underdiagnosed. In this large series of pET, in addition to weight loss and chronic medical conditions, allergy and stress/anxiety were identified as novel risk factors. Most patients can be treated medically.
Duration of Eligibility Prior to Cochlear Implantation: Have We Made Any Progress?
Authors: Appelbaum Eric N. , Yoo Shannon S. , Perera Robert A. , Coelho Daniel H.
Published: August 2017

Objective:

The objective is to determine if eligibility (as defined as the duration of severe to profound hearing loss before cochlear implantation [CI]) has changed over the 30 years since Food and Drug Administration approval.

Data Sources:

English-language, peer-reviewed articles, theses, and trial data available through PubMed and Cochrane Library databases up until and including May 31, 2016.

Study Selection:

One thousand six unique articles were identified. Prospective studies that reported duration of severe/profound hearing loss before CI in adult patients were included. Retrospective studies, reviews, meta-analyses, articles reporting pediatric or mixed data, hybrid/electroacoustic CI, and articles from centers outside the United States were excluded. Seventy-one studies met inclusion criteria and were included for analysis.

Data Extraction:

Contributing authors independently reviewed included studies for data validity and applicability.

Data Synthesis:

Metaregression was used to assess the relationship between the year of publication and duration of hearing loss. To account for a possible age effect, a second model was estimated including mean age at the time of study as a covariate.

Conclusion:

A positive association between study year and the duration of hearing loss before implantation was found showing a 0.28-year increase in the duration of hearing loss for every increasing study year. Contrary to conventional assumption, duration of eligibility for CI appears to be increasing. Though the reasons for this are not clear, current strategies to increase both awareness and access to CI seem to be falling short.
Orthostatic Hypotension in Patients With Left Ventricular Assist Devices: Acquired Autonomic Dysfunction
Authors: Fudim Marat , Rogers Joseph G. , Frazier-Mills Camille , Patel Chetan B.
Published: August 2017

Contemporary left ventricular assist device (LVAD) technology uses nonphysiologic continuous flow to deliver blood into the circulation. This results in a reduction of pulsatility, which is implicated in some of the commonly associated side effects with LVAD therapy, including hypertension and gastrointestinal arterial-venous malformation with related bleeding. A less frequently observed side effect is orthostatic hypotension (OH) in patients supported with LVAD therapy. We present three cases of OH in patients with LVAD, followed by a discussion on how LVAD therapy may induce autonomic dysfunction.
Celecoxib-induced Liver Injury
Authors: Mukthinuthalapati Pavan K. , Fontana Robert J. , Vuppalanchi Raj , Chalasani Naga , Ghabril Marwan
Published: August 2017

Background:

Celecoxib is a widely prescribed nonsteroidal anti-inflammatory drug, and has been associated with rare instances of idiosyncratic drug-induced liver injury (DILI). The aim of this study is to describe and analyze the salient features of published cases of celecoxib DILI.

Materials and Methods:

A literature search using common terms for liver injury cross-referenced with celecoxib was undertaken from the year 2000 through June 2016. Identified cases were analyzed with respect to reported demographic and clinical data with descriptive.

Results:

Celecoxib DILI was reported in 18 patients with a median age of 54 years (range, 29 to 84) and 15 (88%) were female. The median daily dose was 200 mg (range, 200 to 533), and median duration and latency were 13 days (1 to 730) and 17 days (2 to 730), respectively. In 15 (83%) cases, DILI occurred after relatively short treatment duration, median of 12 days (1 to 42). Rash and immunoallergic features were noted in these patients, with peripheral or histologic findings of eosinophilia in 6 (40%). In 3 cases, DILI occurred after prolonged exposure (range, 152 to 730 d), none with immunoallergic features. The pattern of liver injury included hepatocellular (6), mixed (5), and cholestatic (4), and was unknown in 3 cases. Clinical outcomes included 2 (11%) requiring liver transplantation, 4 (22%) with chronic liver injury and recovery in 12 (67%) cases.

Conclusions:

Women are overrepresented in published reports of celecoxib DILI. Latency was short (<3 mo) in most patients but some subjects may present with DILI following prolonged celecoxib use. Although rare, celecoxib-DILI can have potentially life threatening consequences.
Using Skin Gene Markers for Estimating Early Postmortem Interval at Different Temperatures
Authors: Ali Mona Mohamed , Ibrahim Samah Fathy , Fayed Amel Ahmed
Published: August 2017

Many researches document long-term RNA persistence in a variety of tissues and its applicability in estimating the postmortem interval (PMI). Skin-specific mRNA marker, late cornified envelope 1C (LCE1C), was used to identified skin samples. Before using the LCE1C in criminal casework, its persistence and applicability for estimating PMI in different temperatures were tested. Twelve skin samples were collected from 6 patients, and 6 samples were kept at 24°C and others were kept at 40°C for 5 days. The expression levels of LCE1C mRNA are serially detected and quantified using real-time polymerase chain reaction. The expression levels of LCE1C were decreased with increasing the time interval in time-dependent manner, whereas changing the surrounding temperatures did not show any statistical significance. These results could suggest using LCE1C in estimation of PMI. Moreover, these encourage investigators and crime laboratories to know environmental conditions before interpreting the results.
Genomic Analysis of Pigmented Epithelioid Melanocytomas Reveals Recurrent Alterations in PRKAR1A, and PRKCA Genes
Authors: Cohen Jarish N. , Joseph Nancy M. , North Jeffrey P. , Onodera Courtney , Zembowicz Artur , LeBoit Philip E.
Published: August 2017

Pigmented epithelioid melanocytoma (PEM) is a rare cutaneous melanocytic tumor first described as epithelioid blue nevus in patients with the Carney Complex (CC). PEM was among the first established examples of an intermediate class of melanocytic tumors, including atypical Spitz tumors, with frequent metastasis to lymph nodes but only rare extranodal spread. Sporadic and CC-associated PEM are essentially histologically indistinguishable. A subset of PEM shows loss of cytoplasmic expression of the protein kinase A regulatory subunit alpha (PRKAR1A), a tumor suppressor gene mutated in 70% of families with CC. However, molecular studies of such tumors have been limited. Therefore, we used next-generation sequencing to assess 480 cancer-related genes and performed PrkaR1α immunohistochemistry on 13 cases morphologically consistent with PEM. Six cases demonstrated loss of PrkaR1α expression by immunohistochemistry. Three cases were “combined” PEM arising in association with a common nevus. These lesions harbored PRKAR1A genetic alterations in addition to BRAF mutations. Three “pure” PEM, not associated with a common nevus, showed no evidence of PRKAR1A genetic alterations despite loss of PrkaR1α expression. Two of these PEM demonstrated MAP2K1 in frame deletions. PrkaR1α protein expression was preserved in 7 cases. Two of these lesions revealed fusions of the gene encoding the protein kinase C alpha isoform (PRKCA) to 2 distinct partners (ATP2B4-PRKCA and RNF13-PRKCA). Two lesions may represent misdiagnosed “blue nevus with epithelioid features” as they demonstrated GNAQ hotspot mutations. A conceivable explanation, but one we do not favor is that rare PEM are caused by GNAQ mutations. No genetic aberrations were detected in 3 lesions. None of our 13 cases demonstrated TERT alterations or significant chromosomal copy number changes. These results further validate the concept of PEM as a distinctive intermediate/borderline melanocytic tumor, and also illustrate its molecular heterogeneity.
Paraduodenal Pancreatitis
Authors: Muraki Takashi , Kim Grace E. , Reid Michelle D. , Mittal Pardeep , Bedolla Gabriela , Memis Bahar , Pehlivanoglu Burcin , Freedman Alexa , Erbarut Seven Ipek , Choi Hyejeong , Kooby David , Maithel Shishir K. , Sarmiento Juan M. , Krasinskas Alyssa , Adsay Volkan
Published: August 2017

Clinicopathologic characteristics of paraduodenal (groove) pancreatitis (PDP) remain to be fully unraveled. In this study, 47 PDPs with preoperative enhanced images available were subjected to detailed comparative analysis in conjunction with pathologic findings. PDP were predominantly in males (3:1) with a mean age of 50 years, and 60% had a preoperative diagnosis of cancer. Mean lesional size was 3.1 cm. Three distinct subtypes were identified by imaging. Solid-tumoral (type-1) with groove-predominant (type-1A, 36%) forming a distinct solid band between the duodenum and pancreas often with histologic microabscesses (69% vs. 33% in others), and pancreas-involving (type-1B, 19%) forming a pseudotumoral mass spanning into the head-groove area, always diagnosed preoperatively as “cancer,” but often lacked parenchymal atrophy of the body (44% vs. 92%). Cyst-forming (type-2) had groove-predominant (type-2A, 15%), often accompanied by Brunner gland hyperplasia, and pancreas-predominant (type-2B, 15%) were in younger (mean: 44 y) females (57% vs. 18%) and had less alcohol/tobacco abuse (50/33% vs. 81/69%). Ill-defined (type-3; 15%) often had main pancreatic duct dilatation (mean: 5.6 vs. 2.8 mm). The capricious presentations of PDP could be attributed to variable effects of different mechanistic and precipitative etiopathogenetic factors such as disturbed accessory duct outflow (dilated Santorini duct, 87%), aggravated by alcohol (77%) with superimposed stasis in the main ampulla (previous cholecystectomy, 47%; choledocholithiasis, 9%), strictured Wirsung duct (68%), and some likely exacerbated by ischemia (hypertension [59%], tobacco abuse [64%], arteriosclerosis in the tissue [23%]). In conclusion, our study identified 3 distinct types of PDP and each may reflect different pathogenetic contributing factors.
An Intensive, Simulation-Based Communication Course for Pediatric Critical Care Medicine Fellows
Authors: Johnson Erin M. , Hamilton Melinda F. , Watson R. Scott , Claxton Rene , Barnett Michael , Thompson Ann E. , Arnold Robert
Published: August 2017

Objective:

Effective communication among providers, families, and patients is essential in critical care but is often inadequate in the PICU. To address the lack of communication education pediatric critical care medicine fellows receive, the Children’s Hospital of Pittsburgh PICU developed a simulation-based communication course, Pediatric Critical Care Communication course. Pediatric critical care medicine trainees have limited prior training in communication and will have increased confidence in their communication skills after participating in the Pediatric Critical Care Communication course.

Design:

Pediatric Critical Care Communication is a 3-day course taken once during fellowship featuring simulation with actors portraying family members.

Setting:

Off-site conference space as part of a pediatric critical care medicine educational curriculum.

Subjects:

Pediatric Critical Care Medicine Fellows.

Interventions:

Didactic sessions and interactive simulation scenarios.

Measurements and Main Results:

Prior to and after the course, fellows complete an anonymous survey asking about 1) prior instruction in communication, 2) preparedness for difficult conversations, 3) attitudes about end-of-life care, and 4) course satisfaction. We compared pre- and postcourse surveys using paired Student t test. Most of the 38 fellows who participated over 4 years had no prior communication training in conducting a care conference (70%), providing bad news (57%), or discussing end-of-life options (75%). Across all four iterations of the course, fellows after the course reported increased confidence across many topics of communication, including giving bad news, conducting a family conference, eliciting both a family’s emotional reaction to their child’s illness and their concerns at the end of a child’s life, discussing a child’s code status, and discussing religious issues. Specifically, fellows in 2014 reported significant increases in self-perceived preparedness to provide empathic communication to families regarding many aspects of discussing critical care, end-of-life care, and religious issues with patients’ families (p < 0.05). The majority of fellows (90%) recommended that the course be required in pediatric critical care medicine fellowship.

Conclusions:

The Pediatric Critical Care Communication course increased fellow confidence in having difficult discussions common in the PICU. Fellows highly recommend it as part of PICU education. Further work should focus on the course’s impact on family satisfaction with fellow communication.
Eosinophilic Cells, Autoimplants, Degree of Cellular Proliferation, and Adenofibroma Pattern are Important Histologic Findings in Ovarian Borderline Tumors
Authors: Karpathiou Georgia , Venet Melany , Chauleur Celine , Honeyman Fressia , Casteillo Francois , Peoc’h Michel
Published: August 2017

Ovarian borderline tumors can show histologic features, such as different degrees of cellular proliferation, eosinophilic cells, autoimplants, and adenofibromatous architecture, the importance of which is not known. The aim of the study was to describe these features and correlate them with clinical characteristics. Eighty-three ovarian borderline tumors were studied for the aforementioned features. These were correlated with clinicopathologic features. Epithelial proliferation was associated with the T stage in serous tumors (P=0.0009), but not in mucinous tumors (P=0.97). It was positively associated with bilateral tumors (P=0.01) and the presence of autoimplants (P<0.0001). It was associated with the presence of eosinophilic cells, as tumors with extensive eosinophilic cells had a mean proliferation of 80.7%, for those with no such cells it was 23.8% (P<0.0001), and for those with a limited presence of eosinophilic cells it was 48.7% (P=0.03). Cellular proliferation was not associated with the size of the tumor. An adenofibromatous architecture was associated with unilateral tumors (P=0.02) and showed a trend (P=0.08) with regard to T stage in serous tumors. It was not associated with the size of the tumor. The presence of autoimplants was marginally associated (P=0.07) with bilateral tumors and it was not associated with the size of the tumor or the T stage. The presence of eosinophilic cells was not associated with the T stage, the size of the tumor, or bilateral tumors. The degree of epithelial proliferation, autoimplants, adenofibromatous architecture, and the presence of eosinophilic cells are important features in ovarian borderline tumors.
Different Exposures to Risk Factors Do Not Explain the Inverse Relationship of Occurrence Between Cancer and Neurodegenerative Diseases
Authors: Prinelli Federica , Adorni Fulvio , Leite Maria Lea Correa , Pettenati Carla , Russo Antonio , Di Santo Simona , Musicco Massimo
Published: August 2017

Several studies reported that cancer is less frequent in persons with Alzheimer's and Parkinson's Diseases (AD/PD) and vice-versa. We evaluated whether a different distribution of known nongenetic risk factors for cancer and AD/PD, might explain their inverse relationship of occurrence. We nested 2 case-control studies in a subsample of a large cohort of 1,000,000 resident in Lombardy Region in Italy (n=1515), followed-up for cancer and AD/PD occurrence since 1991 until 2012. Conditional logistic regression was performed to determine the odds ratios (OR) and 95% confidence intervals (CI) of AD/PD in subjects with and without cancer and the risk of cancer in those with and without AD/PD. A total of 54 incident cases of AD/PD and 347 cancer cases were matched with 216 and 667 controls, respectively. After controlling for low education, obesity, history of hypertension, diabetes, dyslipidemia, physical activity, smoking habit, alcohol consumption, and dietary habit, cancer was found inversely associated with the risk of AD/PD (OR, 0.66; 95% CI, 0.32-1.38), and the risk of cancer in AD/PD was similarly reduced (OR, 0.42; 95% CI, 0.20-0.91). Different exposures to nongenetic risk factors of both diseases do not explain their competitive relationship of occurrence.
Ocean deoxygenation, the global phosphorus cycle and the possibility of human-caused large-scale ocean anoxia
Authors: Watson Andrew J. , Lenton Timothy M. , Mills Benjamin J. W.
Published: August 2017

The major biogeochemical cycles that keep the present-day Earth habitable are linked by a network of feedbacks, which has led to a broadly stable chemical composition of the oceans and atmosphere over hundreds of millions of years. This includes the processes that control both the atmospheric and oceanic concentrations of oxygen. However, one notable exception to the generally well-behaved dynamics of this system is the propensity for episodes of ocean anoxia to occur and to persist for 10
5
–10
6
years, these ocean anoxic events (OAEs) being particularly associated with warm ‘greenhouse’ climates. A powerful mechanism responsible for past OAEs was an increase in phosphorus supply to the oceans, leading to higher ocean productivity and oxygen demand in subsurface water. This can be amplified by positive feedbacks on the nutrient content of the ocean, with low oxygen promoting further release of phosphorus from ocean sediments, leading to a potentially self-sustaining condition of deoxygenation. We use a simple model for phosphorus in the ocean to explore this feedback, and to evaluate the potential for humans to bring on global-scale anoxia by enhancing P supply to the oceans. While this is not an immediate global change concern, it is a future possibility on millennial and longer time scales, when considering both phosphate rock mining and increased chemical weathering due to climate change. Ocean deoxygenation, once begun, may be self-sustaining and eventually could result in long-lasting and unpleasant consequences for the Earth's biosphere.

This article is part of the themed issue ‘Ocean ventilation and deoxygenation in a warming world’.
Ventilation variability of Labrador Sea Water and its impact on oxygen and anthropogenic carbon: a review
Authors: Rhein Monika , Steinfeldt Reiner , Kieke Dagmar , Stendardo Ilaria , Yashayaev Igor
Published: August 2017

Ventilation of Labrador Sea Water (LSW) receives ample attention because of its potential relation to the strength of the Atlantic Meridional Overturning Circulation (AMOC). Here, we provide an overview of the changes of LSW from observations in the Labrador Sea and from the southern boundary of the subpolar gyre at 47° N. A strong winter-time atmospheric cooling over the Labrador Sea led to intense and deep convection, producing a thick and dense LSW layer as, for instance, in the early to mid-1990s. The weaker convection in the following years mostly ventilated less dense LSW vintages and also reduced the supply of oxygen. As a further consequence, the rate of uptake of anthropogenic carbon by LSW decreased between the two time periods 1996–1999 and 2007–2010 in the western subpolar North Atlantic. In the eastern basins, the rate of increase in anthropogenic carbon became greater due to the delayed advection of LSW that was ventilated in previous years. Starting in winter 2013/2014 and prevailing at least into winter 2015/2016, production of denser and more voluminous LSW resumed. Increasing oxygen signals have already been found in the western boundary current at 47° N. On decadal and shorter time scales, anomalous cold atmospheric conditions over the Labrador Sea lead to an intensification of convection. On multi-decadal time scales, the ‘cold blob’ in the subpolar North Atlantic projected by climate models in the next 100 years is linked to a weaker AMOC and weaker convection (and thus deoxygenation) in the Labrador Sea.

This article is part of the themed issue ‘Ocean ventilation and deoxygenation in a warming world’.
High-latitude ocean ventilation and its role in Earth's climate transitions
Authors: Naveira Garabato Alberto C. , MacGilchrist Graeme A.  , Brown Peter J. , Evans D. Gwyn , Meijers Andrew J. S. , Zika Jan D.
Published: August 2017

The processes regulating ocean ventilation at high latitudes are re-examined based on a range of observations spanning all scales of ocean circulation, from the centimetre scales of turbulence to the basin scales of gyres. It is argued that high-latitude ocean ventilation is controlled by mechanisms that differ in fundamental ways from those that set the overturning circulation. This is contrary to the assumption of broad equivalence between the two that is commonly adopted in interpreting the role of the high-latitude oceans in Earth's climate transitions. Illustrations of how recognizing this distinction may change our view of the ocean's role in the climate system are offered.

This article is part of the themed issue ‘Ocean ventilation and deoxygenation in a warming world’.
Intron-containing RNA from the HIV-1 provirus activates type I interferon and inflammatory cytokines
Authors: McCauley Sean Matthew , Kim Kyusik , Nowosielska Anetta , Dauphin Ann , Yurkovetskiy Leonid , Diehl William Edward , Luban Jeremy
Published: August 2017

HIV-1-infected people who take drugs that suppress viremia to undetectable levels are protected from developing AIDS. Nonetheless, these individuals have chronic inflammation associated with heightened risk of cardiovascular pathology. HIV-1 establishes proviruses in long-lived CD4+memory T cells, and perhaps other cell types, that preclude elimination of the virus even after years of continuous antiviral therapy. Though the majority of proviruses that persist during antiviral therapy are defective for production of infectious virions, many are expressed, raising the possibility that the HIV-1provirus or its transcripts contribute to ongoing inflammation. Here we found that the HIV-1 provirus activated innate immune signaling in isolated dendritic cells, macrophages, and CD4+T cells. Immune activation required transcription from the HIV-1 provirus and expression of CRM1-dependent, Rev-dependent, RRE-containing, unspliced HIV-1 RNA. Ifrevwas providedin trans, all HIV-1 coding sequences were dispensable for activation except thosecis-acting sequences required for replication or splicing. These results indicate that the complex, post-transcriptional regulation intrinsic to HIV-1 RNA is detected by the innate immune system as a danger signal, and that drugs which disrupt HIV-1 transcription or HIV-1 RNA metabolism would add qualitative benefit to current antiviral drug regimens.
Molecular machinery of auxin synthesis, secretion, and perception in the unicellular chlorophyte algaChlorella sorokinianaUTEX 1230
Authors: Khasin Maya , Cahoon Rebecca R. , Nickerson Kenneth W. , Riekhof Wayne R.
Published: August 2017

Indole-3-acetic acid is a ubiquitous small molecule found in all domains of life. It is the predominant and most active auxin in seed plants, where it coordinates a variety of complex growth and development processes. The potential origin of auxin signaling in algae remains a matter of some controversy. In order to clarify the evolutionary context of algal auxin signaling, we undertook a genomic survey to assess whether auxin acts as a signaling molecule in the emerging model chlorophyteChlorella sorokinianaUTEX 1230.C. sorokinianaproduces the auxin indole-3-acetic acid (IAA), which was present in both the cell pellet and in the supernatant at a concentration of ~ 1 nM, and its genome encodes orthologs of genes related to auxin synthesis, transport, and signaling in higher plants. Candidate orthologs for the canonical AUX/IAA signaling pathway were not found; however, auxin-binding protein 1 (ABP1), an alternate auxin receptor, is present and highly conserved at essential auxin binding and zinc coordinating residues. Additionally, candidate orthologs for PIN proteins, responsible for intercellular, vectorial auxin transport in higher plants, were not found, but PILs (PIN-Like) proteins, a recently discovered family that mediates intracellular auxin transport, were identified. The distribution of auxin related gene in this unicellular chlorophyte demonstrates that a core suite of auxin signaling components was present early in the evolution of plants. Understanding the simplified auxin signaling pathways in chlorophytes will aid in understanding phytohormone signaling and crosstalk in seed plants, and in understanding the diversification and integration of developmental signals during the evolution of multicellular plants.