bluuebunny/crossref_metadata_2025 huggingface dataset:
Emergent airway management of the critically ill patient: current opinion in critical care
Authors: Sklar Michael C. , Detsky Michael E.
Published: September 2019

Purpose of review

To describe techniques to facilitate safe intubation in critically ill patients.

Recent findings

Despite advances in the treatment of critically ill patients, endotracheal intubation remains a high-risk procedure associated with complications that can lead to appreciable morbidity and mortality. In addition to the usual anatomical factors that can predict a difficult intubation, incorporating pathophysiological considerations and crisis resource management may enhance safety and mitigate risk. Enhancing preoxygenation with high-flow oxygen or noninvasive ventilation, the early use of intravenous fluids and/or vasopressors to prevent hypotension and videolaryngoscopy for first pass success are all promising additions to airway management.

Facilitating intubation by either sedation with paralysis or allowing patients to continue to breathe spontaneously are reasonable options for airway management. These approaches have potential advantages and disadvantages.

Recognizing the unique challenges of endotracheal intubation in critically ill patients is paramount in limiting further deterioration during this high-risk procedure. A safe approach to intubation focuses on recognizing risk factors that predict challenges in achieving an optimal view of the glottis, maintaining optimal oxygenation, and minimizing the risks and benefits of sedation/induction strategies that are meant to facilitate intubation and avoid clinical deterioration.
Individual resection and reconstruction of pelvic tumor with three-dimensional printed customized hemi-pelvic prosthesis
Authors: Han Qing , Zhang Kesong , Zhang Yong , Wang Chenyu , Yang Kerong , Zou Yun , Chen Bingpeng , Wang Jincheng
Published: September 2019

Rationale:

Pelvic tumor had great impact on patients’ quality of life. After tumor resection, how to accurately fill bone defect remained challenging for orthopedic surgeons. Due to lack of individual design, high incidence of prosthetic mismatching, and loosening were reported in pelvic reconstruction surgery with conventional modular prostheses. Nowadays, with rapid development of three-dimensional (3D) print technology, pelvic prostheses could be designed according to patients’ own anatomy. The objective of this study was to describe the application of 3D printed customized hemi-pelvic prosthesis for patients with pelvic tumor.

Patient concerns:

A 62-year-old female had developed severe right joint pain without obvious inducement from 5 months before she sought medical advice. Pain, swelling, and limited range of motion of right joint were founded during physical examination.

Diagnosis:

The patients were diagnosed as “right acetabulum metastatic carcinoma”

Intervention:

3D printed titanium alloy hemi-pelvic prosthesis was designed according the morphology of unaffected side hemi-pelvis and subsequently implanted in surgery to reconstruct the pelvis. 3D printed osteotomy guide and pelvic model were also manufactured and applied to improve accuracy of osteotomy and reduce operation time. X-Ray of pelvis, Harris score, musculoskeletal tumor society score (MSTS) and The MOS item short from health survey (SF-36) were recorded during the period of preoperation, 1, 3, 6, 12 months follow-up after operation.

Outcomes:

3D printed hemi-pelvic prosthesis matched precisely with pelvis and implanted successfully. There was no sign of prosthetic loosening within 12 months’ follow-up. No sign of peri-prosthetic infection from laboratory examination. Harris score, MSTS, and SF-36 were gradually increasing during follow-up period.

Lessons:

Satisfactory effect of pelvic reconstruction could be achieved by 3D printed hemi-pelvic prostheses. It also provided a promising way to the treatment of pelvic tumor in similar cases.
Bereavement practices employed by hospitals and medical practitioners toward attending funeral of patients
Authors: Kim Kwangtaek , Churilov Leonid , Huang Andrew , Weinberg Laurence
Published: September 2019

Objectives:

To ascertain bereavement practices offered by hospitals and medical practitioners (MPs), factors that influence the likelihood of MPs’ involvement in funeral attendance, the benefits and barriers to attendance to a patient's funeral as perceived by MPs and the rate of attendance to patients’ funeral by MPs.

Design:

MEDLINE (Ovid), Embase, PubMed, and Google Scholar were searched with a systematic search structure for randomized controlled trials, comparative observational studies, case series, cross-sectional studies, editorials, and letters. The search was limited to English only. The study was registered with Prospero (Registration Number: CRD42018095368).

Results:

A total of 381 articles were identified with 46 articles meeting the inclusion criteria. Of the 46, 16 were editorials and 12 were letters. Eighteen were cross-sectional studies conducted in the United States, Canada, Australia, Israel, and Ireland. Year of publication ranged from 1990 to 2017. Of these, 12 were quantitative, 3 were qualitative, and 3 were mixed-method studies. Two of the cross-sectional studies involved family members of deceased patients while others involved MPs. Bereavement practices offered by hospitals included memorial services, letters, and services provided by bereavement coordinators. Bereavement practices employed by MPs included answering or making phone calls, attending family meetings, and sending condolence letters. MPs’ attendance at a patient's funeral was influenced by MPs’ gender, age years of experience the medical specialty. Perceived benefits of MPs’ attendance at a patient's funeral included providing support to the family, extending the professional relationship, illustrating respect to the patient and the family, resolving guilt and personal growth. Barriers to the attendance included a lack of time, blurring of professional boundaries, personal discomfort with death, emotional arousal, and discouragement by colleagues. General practice had an attendance rate of 71%. Attendance rates for palliative care, oncology, and psychiatrists ranged from 63% to 81%, 7.1% to 67%, and 15% to 67%, respectively. Intensivists had an attendance rate of 22%.

Conclusion:

Several bereavement practices are provided by hospitals and MPs. Funeral attendance is an uncommon bereavement practice. MPs’ attitudes toward attending a patient's funeral are understudied in many specialties. Patient factors that influence MPs’ participation in bereavement practices are poorly understood.
Increased expression of miR-153 predicts poor prognosis for patients with prostate cancer
Authors: Bi Cheng-wei , Zhang Guo-ying , Bai Yu , Zhao Bin , Yang Hong
Published: September 2019

Deregulation of miR-153 has recently been observed in several common human cancer, while miR-153 serves an oncogene or tumor suppressive role in different cancer types. Previously, miR-153 has been identified to be overexpressed in prostate cancer. miR-153 played an important role in promoting proliferation of human prostate cancer cells and presented a novel mechanism of microRNA-mediated direct suppression of phosphatase and tensin homolog (PTEN) expression in prostate cancer cells. Until now, little is known about the clinical significance of miR-153 expression in prostate cancer.

The miR-153 expression in 143 pairs of prostate cancer and adjacent non-cancerous prostate tissues was measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis. Student t test was conducted for intergroup comparison. Pearson correlation test was used for correlation analysis. Survival curves were carried out by the Kaplan–Meier method and evaluated using the log-rank test. Multivariable Cox proportional hazard risk regression model was performed to screen the independent factor affected the prognosis of prostate cancer patients.

qRT-PCR analysis showed that the expression of miR-153 was significantly increased in the prostate cancer tissues in comparison with the adjacent noncancerous prostate tissues (P < .001). The high expression of miR-153 in prostate cancer tissues is closely correlated with aggressive clinical pathological parameters such as lymph node metastasis (P = .001); bone metastasis (P < .001); Gleason score (P < .001); and tumor-node-metastasis (TNM) stage (P < .001). Prostate cancer patients with a high expression of miR-153 had an evidently lower 5-year overall survival as compared with those with a low expression of miR-153 (P = .019). Notably, the multivariate Cox regression analysis indicated that miR-153 expression was an independent factor for predicting the 5-year overall survival of prostate cancer patients (hazard ratio [HR] = 2.481, 95% confidence interval [CI]: 1.582–10.727; P = .018).

Our study demonstrated that high miR-153 expression was significantly associated with a poor overall survival independently of other factors in prostate cancer. Therefore, miR-153 may be an available biomarker for prostate cancer prognosis.
Computed tomographic findings of macrolide-resistant Mycobacterium massiliense pulmonary disease and changes after antibiotic treatment
Authors: Yoon Hyun Jung , Chung Myung Jin , Koh Won-Jung , Jhun Byung Woo , Moon Seong Mi
Published: September 2019

The purpose of this study was to present the computed tomographic (CT) findings of lung abnormalities in macrolide-resistant Mycobacterium massiliense pulmonary disease and its changes in follow-up CT after antibiotic treatment.

Chest CT scans of patients with macrolide-resistant M massiliense pulmonary disease (n = 19) were retrospectively reviewed. Patients were treated with multidrug therapy, and sputum examinations were performed. Follow-up CT scans obtained during antibiotic treatment after detection of macrolide resistance were also reviewed, if available (n = 13). The CT scores at detection of macrolide resistance and at the last follow-up periods were also compared.

Of all patients with macrolide-resistant M massiliense pulmonary disease, 2 (11%) patients achieved sputum culture conversion during the follow-up period. The most common CT findings of M massiliense pulmonary disease at detection of macrolide resistance were bronchiectasis and bronchiolitis (n = 19, 100%), followed by consolidation (n = 16, 84%), cavities (n = 11, 58%), and nodules (n = 6, 32%). On the last follow-up CT, overall CT scores were increased in 8 (62%) of 13 patients, and total mean CT score was significantly increased (P = .021). For each CT pattern, the cavity showed the greatest increase in CT score (P = .027), followed by bronchiectasis (P = .038).

Common CT findings of macrolide-resistant M massiliense pulmonary disease were similar to those of pulmonary disease caused by other species of nontuberculous mycobacteria at presentation. However, in macrolide-resistant M massiliense pulmonary disease, serial CT scans showed deterioration with cavitary and bronchiectatic change in most patients despite multidrug antibiotic therapy.
Effects of a 12-week moderate-intensity exercise training on blood glucose response in patients with type 2 diabetes
Authors: Chiang Shang-Lin , Heitkemper Margaret McLean , Hung Yi-Jen , Tzeng Wen-Chii , Lee Meei-Shyuan , Lin Chia-Huei
Published: September 2019

Background:

The blood glucose response to moderate-intensity exercise remains unclear for patients with type 2 diabetes (T2DM). In addition, little is known about determinants of blood glucose response to a 12-week moderate-intensity exercise training. Therefore, this study aimed to explore trends in blood glucose in response to a 12-week moderate-intensity exercise training in patients with T2DM and to explore the predictors of post-exercise blood glucose (PEBG) and exercise-induced glucose response (EIGR).

Methods:

A prospective longitudinal study was conducted. Of the 66 participants with T2DM recruited from outpatient clinics of a medical center, 20 were eligible to enroll in a 12-week moderate-intensity exercise training. Participants were randomly assigned to 1 of 3 exercise times (morning, afternoon, or evening). Blood glucose were measured pre- and post-exercise. The EIGR was calculated by subtracting the PEBG from the before-exercise blood glucose (BEBG). Generalized estimating equations were used to examine the trends and predictors of PEBG and EIGR.

Results:

The BEBG declined progressively (β = −1.69, P < .001); while the PEBG (β = −0.18, P = .08) remained stable over time during the 12-week exercise training. Higher BEBG predicted higher (β = 0.53, P < .001) PEBG. Higher baseline maximum oxygen uptake (VO2max) contributed to a larger magnitude of EIGR; higher HgbA1c and BEBG predicted higher EIGR (β = 0.27, P = .02; β = 0.45, P < .001); afternoon or evening exercise predicted lower (β = −13.2, P = .04; β = −5.96, P = .005) EIGR than did morning exercise.

Conclusions:

A 12-week moderate-intensity exercise training appears safe for patients with T2DM. Time of day for exercise, baseline VO2max, and baseline metabolic control may influence the impact of exercise for individuals with T2DM. These findings provide considerations for design of optimal exercise training for T2DM patients.
Multiple intracranial and spinal cord syphilitic gummas in a human immunodeficiency virus-negative man with untreated syphilis
Authors: Shen Sisi , Yang Ruiyi , Wang Libo , Tang Liwei , Liu Bo
Published: September 2019

Rationale:

Multiple syphilitic gummas involving both the brain and spinal cord are quite rare. Central nervous system (CNS) syphilitic gummas are commonly misdiagnosed as CNS tumors, and clinical suspicion and diagnosis of a syphilitic gumma by physicians are vital to avoiding unnecessary surgeries. Our case emphasizes the importance of routine serologic syphilis tests and standard therapy with penicillin in patients with a CNS mass.

Patient concerns:

A 22-year-old previously healthy man presented with a 9-day history of progressive right lower limb weakness.

Diagnosis:

The diagnosis of gummatous neurosyphilis was based on positive serological, cerebrospinal fluid tests for syphilis and magnetic resonance imaging (MRI) findings, which revealed the presence of multiple dural-based enhancing masses with marked edema.

Interventions:

Therapy consisting of intravenous penicillin G at 24 million units daily divided into 6 doses were given for a total of 21 days, along with 3 weekly intramuscular injections of benzathine penicillin G (2.4 million units) to ensure that the syphilitic lesions in the CNS were adequately treated.

Outcomes:

Complete resolution of the lesions was observed on MRI over a 3-month period.

Lessons:

The importance of routine serologic syphilis tests and standard therapy with penicillin in patients with central CNS mass lesions is noted to avoiding unnecessary surgeries.
Elevated expression of MTDH predicts better prognosis of locally advanced HER-2 positive breast cancer patients receiving neoadjuvant chemotherapy plus trastuzumab
Authors: Wang Xinle , Cai Lijing , Ye Feng , Li Mengqi , Ma Li , Geng Cuizhi , Song Zhenchuan , Liu Yueping
Published: September 2019

Metadherin (MTDH), also known as astrocyte elevated gene-1 (AEG-1), is an oncoprotein closely related to the development of breast cancer. However, few studies have been done on the expression and clinical significance of MTDH in human epidermal growth factor receptor-2 (HER-2) positive breast cancer patients.

This study aimed to investigate the expression of MTDH in locally advanced HER-2 positive breast cancer, and evaluate the clinical significance of MTDH in predicting the prognosis of patients with HER-2 positive advanced breast cancer who received the neoadjuvant chemotherapy plus trastuzumab.

In 144 HER-2 positive breast cancer tissues, 79 cases showed high expression of MTDH and 65 cases showed low expression. The expression of MTDH in locally advanced HER-2 positive breast cancer tissues was correlated with TNM stage, lymph node metastasis, Miller-Payne (MP) grade, and pathologic complete response (pCR) status (P < .05), but was not correlated with patient age, estrogen receptor (ER) expression level, progesterone receptor (PR) expression level, and Ki-67 expression level (P > .05). Kaplan–Meier univariate analysis revealed a negative correlation between MTDH expression and the disease-free survival (DFS) and overall survival (OS) in the post-operative patients with locally advanced HER-2 positive breast cancer (log rank test: P < .001). By using the COX proportional hazard regression model, it was found that MTDH expression, TNM stage, lymph node metastasis, and Ki-67 expression were closely related to DFS in patients. The hazard ratio (HR) of high MTDH expression was 1.816 (95% CI: 1.165–2.829). In addition, MTDH expression, TNM stage, and lymph node metastasis were also closely related to the OS of patient. The HR of the high expression of MTDH was 2.512 (95% CI: 1.472–4.286). The expression of MTDH in tumor tissues of patients with HER2-positive locally advanced breast cancer was significantly elevated, which was related to the poor pathological features.

High MTDH expression was closely correlated with poor prognosis of patients and was an important factor affecting tumor progression.
Synthetic cannabinoid-associated coagulopathy secondary to long-acting anticoagulant rodenticides
Authors: Bahouth Mona N. , Kraus Peggy , Dane Kathryn , Plazas Montana Manuela , Tsao William , Tabaac Burton , Jasem Jagar , Schmidlin Holly , Einstein Evan , Streiff Michael B. , Shanbhag Satish
Published: September 2019

Synthetic cannabinoids have become increasingly popular drugs of abuse due to low cost and inability to detect these substances on routine drug screenings. In the United States, incidence of synthetic cannabinoid contamination with long-acting anticoagulant rodenticides (LAARs) resulting in coagulopathy and bleeding complications has been described.

We sought to describe the natural history, management approach, and outcomes of bleeding secondary to synthetic cannabinoid-associated LAAR toxicity in an observational case series of patients evaluated at an urban academic medical system.

We conducted an observational study of patients with suspected exposure to LAAR-contaminated synthetic cannabinoids and associated bleeding treated within the Johns Hopkins Health System.

In this 16 subject cohort, hematuria was the most common bleeding symptom at presentation. The majority of the cohort (75%) had international normalized ratio (INR) > 9.6 at presentation. Of the 13 patients with brodifacoum testing, 12/13 (92%) were positive. Twelve patients (75%) had at least 1 INR value below 2 within 24 hours of the first INR measurement. Of this cohort, 1/16 (6%) died in hospital. The median length of hospital stay was 4 days, (interquartile range = 3–6). The average cost of pharmacological treatment for coagulopathy during inpatient hospitalization was $5300 (range, $2241–$8086).

In patients presenting with unexplained coagulopathy it is important for emergency department providers to consider LAAR intoxication and consider formal testing for brodifacoum to assist with treatment planning. Use of a standardized management algorithm including intravenous/oral vitamin K, judicious use of blood products and close laboratory monitoring is essential to optimizing outcomes.
Clinical features and prognostic analysis of patients with chest wall chondrosarcoma
Authors: Gao Hongliang , Zhou Yuanxi , Wang Zhan , Zhao Renbo , Qian Shengjun
Published: September 2019

Chest wall chondrosarcoma is a rare malignant tumor of the bone. This study is aimed to identify the prognostic determinants of chest wall chondrosarcoma. We used the Surveillance, Epidemiology, and End Results (SEER) database to identify patients with chest wall chondrosarcoma from 1973 to 2015. Statistical analyses were performed using Kaplan–Meier method and Cox regression proportional hazards. A total of 779 patients were identified from the SEER database. The overall survival (OS) and cancer-specific survival (CSS) rates of the entire group at 10 years were 66.2% and 77.2%, respectively. On multivariate Cox regression, age ≤40 years, localized tumor stage, low tumor grade, surgery, and no radiotherapy were significantly associated with improved both OS and CSS. This study may help clinicians to predict survival of patients with chest wall chondrosarcoma and to provide appropriate treatment recommendations.
Mucosa-associated lymphoid tissue lymphoma of the accessory parotid gland presenting as a simple cheek mass
Authors: Hwang Jae Ha , Kim Dong Wan , Kim Kwang Seog , Lee Sam Yong
Published: September 2019

Rationale:

Mucosa-associated lymphoid tissue (MALT) lymphoma, also known as extranodal marginal zone B-cell lymphoma, usually occurs in the gastric mucosa, lung, lacrimal glands, and salivary glands. MALT lymphoma arising from the accessory parotid gland is extremely rare and can therefore be easily confused with other types of soft tissue masses.

Patient concerns:

A 56-year-old woman presented with a 1-month history of a mass on the left cheek. The mass was hard and nontender. She had a history of thymectomy 26 years ago due to myasthenia gravis.

Diagnosis:

A soft tissue tumor measuring 2.5 × 0.8 cm was identified in the left accessory parotid gland on ultrasonography and enhanced computed tomography (CT). Additionally, CT revealed enlargement of both lacrimal glands and an enhancing mass in the right retropharyngeal space. Under suspicion of a malignant soft tissue tumor, ultrasonography-guided fine needle aspiration biopsy was performed, with findings suggestive of marginal zone B-cell lymphoma of the accessory parotid gland.

Interventions:

The patient was transferred to the department of hematology for immunochemotherapy.

Outcomes:

The patient has received 6 cycles of rituximab with cyclophosphamide, vincristine, and prednisone chemotherapy. After 6-month follow-up, enhanced CT demonstrated complete remission. Now she is currently under periodic follow-up.

Lessons:

Physicians and surgeons should be aware that MALT lymphoma can occur in the accessory parotid gland. When this is suspected, careful history-taking, imaging workup, and biopsy are essential for accurate diagnosis and treatment.
Effects of low-intensity pulsed ultrasound on recovery of physical impairments, functional performance and quality of life after total knee arthroplasty
Authors: Munajat Munayati , Mohd Nordin Nor Azlin , Mohamad Yahya Nor Hamdan , Zulkifly Ahmad Hafiz
Published: September 2019

Introduction:

The presence of significant pain and swelling during the acute stage following total knee arthroplasty (TKA) may limit the patients’ ability to cooperate in intensive physiotherapy interventions. Low-intensity pulsed ultrasound is one of the modalities that can be used for acute pain and swelling management. However, only one study investigated the effect of this modality in patients with TKA. There is limited documentation of the effects of combining low-intensity pulsed ultrasound in TKA rehabilitation in the recovery of physical impairments and how these influence the recovery of function after TKA. Therefore, this study is proposed with the aim to evaluate the effects of low-intensity pulsed ultrasound as an adjunct to conventional physiotherapy on the recovery of physical impairments, functional performance and quality of life after TKA surgery.

Methods:

This is an assessor-blinded quasi-experimental study comparing two approaches of physiotherapy, namely pulsed ultrasound-added physiotherapy and conventional physiotherapy. Total number of participants with TKA required for this study will be calculated based on the result of a pilot study. Participants will be alternately allocated into either pulsed ultrasound-added physiotherapy group (low-intensity pulsed ultrasound and conventional physiotherapy) or control group (conventional physiotherapy). Pulsed ultrasound-added physiotherapy group will receive low-intensity pulsed ultrasound starting at post-operative day 2 (4–5 times for the first-week after surgery and 2–3 times a week for a further 2 weeks). Both groups will receive conventional physiotherapy 4 to 5 times for the first-week after surgery and 2 to 3 times a week for a further 11 weeks. This procedure and process will be tested and established in a pilot study. Primary outcomes of interest are pain level, swelling, active range of knee motion, and quadriceps strength. The secondary outcomes are functional performance and quality of life.

Discussion:

This study will fill the gaps in knowledge relating the benefits of including low-intensity pulsed ultrasound into conventional physiotherapy for patients with TKA.

Trial registration:

Australian New Zealand Clinical Trials Registry, ACTRN12618001226291
Mechanisms of alloimmunization in sickle cell disease
Authors: Hudson Krystalyn E. , Fasano Ross M. , Karafin Matthew S. , Hendrickson Jeanne E. , Francis Richard O.
Published: September 2019

Purpose of review

Red blood cell (RBC) transfusion is an important treatment for some complications of sickle cell disease (SCD). On the contrary, transfusion may lead to alloimmunization to RBC antigens, with such alloantibodies putting patients at risk for acute or delayed hemolysis, and increasing the difficulty of finding compatible RBCs. Patients with SCD are more susceptible to developing RBC alloantibodies than other multiply transfused patient populations, for reasons that are not completely understood. In this review, we summarize the available data about risk factors and underlying mechanisms associated with RBC alloimmunization in SCD.

Recent findings

Although RBC antigen matching between blood donors and transfusion recipients can decrease alloimmunization, complete matching at all loci is not feasible. Patients with SCD show evidence of increased inflammation at baseline and in times of illness. Resultant changes to the innate and adaptive immune systems presumably influence the development of RBC alloantibodies as well as RBC autoantibodies.

The inflammation and immune dysregulation associated with SCD may be therapeutic targets for preventing the formation of antibodies and/or for mitigating the dangers of existing RBC alloantibodies. As long as RBC transfusion therapy remains an important treatment for SCD, the quest to improve its safety profile will continue.
Herpes Simplex Virus Keratitis
Authors: Harris Karen D.
Published: September 2019

Herpes simplex virus (HSV) is a highly prevalent infection in the United States. One complication of HSV is HSV keratitis, an ocular HSV infection thought to be the leading cause of corneal blindness in the United States. Home care clinicians with knowledge of the signs and symptoms of HSV and HSV keratitis can aid in early detection and treatment of this potentially serious infection. This article discusses signs and symptoms of HSV keratitis, preventive measures, and treatment.
CDX2 Loss With Microsatellite Stable Phenotype Predicts Poor Clinical Outcome in Stage II Colorectal Carcinoma
Authors: Slik Khadija , Turkki Riku , Carpén Olli , Kurki Samu , Korkeila Eija , Sundström Jari , Pellinen Teijo
Published: September 2019

Current risk factors in stage II colorectal carcinoma are insufficient to guide treatment decisions. Loss of CDX2 has been shown to associate with poor clinical outcome and predict benefit for adjuvant chemotherapy in stage II and III colorectal carcinoma. The prognostic relevance of CDX2 in stage II disease has not been sufficiently validated, especially in relation to clinical risk factors, such as microsatellite instability (MSI) status, BRAF mutation status, and tumor budding. In this study, we evaluated the protein expression of CDX2 in tumor center and front areas in a tissue microarrays material of stage II colorectal carcinoma patients (n=232). CDX2 expression showed a partial or total loss in respective areas in 8.6% and 10.9% of patient cases. Patients with loss of CDX2 had shorter disease-specific survival when scored independently either in tumor center or tumor front areas (log rankP=0.012;P=0.012). Loss of CDX2 predicted survival independently of other stage II risk factors, such as MSI status and BRAF mutation status, pT class, and tumor budding (hazard ratio=5.96, 95% confidence interval=1.55-22.95; hazard ratio=3.70, 95% confidence interval=1.30-10.56). Importantly, CDX2 loss predicted inferior survival only in patients with microsatellite stable, but not with MSI-high phenotype. Interestingly, CDX2 loss associated with low E-cadherin expression, tight junction disruption, and high expression of ezrin protein. The work demonstrates that loss of CDX2 is an independent risk factor of poor disease-specific survival in stage II colorectal carcinoma. Furthermore, the study suggests that CDX2 loss is linked with epithelial-to-mesenchymal transition independently of tumor budding.
Incidental Detection of Pleomorphic Sarcoma on 68Ga-PSMA PET/CT in a Patient With Prostate Cancer
Authors: Mathew Boon , Agrawal Archi , Purandare Nilendu C. , Ramadwar Mukta , Menon Santosh , Bakshi Ganesh , Joshi Amit , Puranik Ameya , Shah Sneha , Rangarajan Venkatesh
Published: September 2019

68Ga prostate-specific membrane antigen (PSMA) PET/CT is used in the staging, evaluation of biochemical recurrence, and response assessment of patients with prostate cancer. In addition to the PSMA-expressing prostate cancer cells, Ga-PSMA binds to the neovasculaature of various other solid tumors and benign lesions. We report a case of a 72-year-old man with recently diagnosed adenocarcinoma of prostate, incidentally found to have pleomorphic sarcoma on the staging 68Ga-PSMA PET/CT.
Leveraging a Comprehensive Program to Implement a Colorectal Surgical Site Infection Reduction Bundle in a Statewide Quality Improvement Collaborative
Authors: McGee Michael F. , Kreutzer Lindsey , Quinn Christopher M. , Yang Anthony , Shan Ying , Halverson Amy L. , Love Remi , Johnson Julie K. , Prachand Vivek , Bilimoria Karl Y.
Published: September 2019

Objectives:

Our objective was to examine the implementation and associated clinical outcomes of a comprehensive surgical site infection (SSI) reduction bundle in a large statewide surgical quality improvement collaborative leveraging a multifaceted implementation strategy.

Summary Background Data:

Bundled perioperative interventions reduce colorectal SSI rates when enacted at individual hospitals, but the ability to implement comprehensive SSI bundles and to examine the resultant clinical effectiveness within a larger, diverse population of hospitals is unknown.

Methods:

A multifaceted SSI reduction bundle was developed and implemented in a large statewide surgical quality improvement collaborative through a novel implementation program consisting of guided implementation, data feedback, mentorship, process improvement training/coaching, and targeted-implementation toolkits. Bundle adherence and ACS NSQIP outcomes were examined preimplementation versus postimplementation.

Results:

Among 32 hospitals, there was a 2.5-fold relative increase in the proportion of patients completing at least 75% of bundle elements (preimplementation = 19.5% vs. postimplementation = 49.8%, P = 0.001). Largest adherence gains were seen in wound closure re-gowning/re-gloving (24.0% vs. 62.0%, P < 0.001), use of clean closing instruments (32.1% vs. 66.2%, P = 0.003), and preoperative chlorhexidine bathing (46.1% vs. 77.6%, P < 0.001). Multivariable analyses showed a trend toward lower risk of superficial incisional SSI in the postimplementation period compared to baseline (OR 0.70, 95% CI 0.49–10.2, P = 0.06). As the adherence in the number of bundle elements increased, there was a significant decrease in superficial SSI rates (lowest adherence quintile, 4.6% vs. highest, 1.5%, P < 0.001).

Conclusions:

A comprehensive multifaceted SSI reduction bundle can be successfully implemented throughout a large quality improvement learning collaborative when coordinated quality improvement activities are leveraged, resulting in a 30% decline in SSI rates. Lower superficial SSI rates are associated with the number of adherent bundle elements a patient receives, rendering considerable benefits to institutions capable of implementing more components of the bundle.
Comparative Efficacy of 9 Major Drugs for Postendoscopic Retrograde Cholangiopancreatography Pancreatitis: A Network Meta-Analysis
Authors: Lyu Yunxiao , Wang Bin , Cheng Yunxiao , Xu Yueming , Du Weibing
Published: September 2019

Background:

Postendoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is one of the most common complications after ERCP. The optimal drugs for reducing the risk of PEP are still unclear. This study aimed to compare the efficacy of 9 major drugs used worldwide for the prevention of PEP through a network meta-analysis.

Methods:

We conducted a systematic search of the literature up to October 2018 on PubMed, Embase, Web of Science, the Cochrane Central Library, and ClinicalTrials.gov. Randomized controlled trials (RCTs) comparing allopurinol, diclofenac, gabexate (GAB), glyceryl trinitrate (GTN), indomethacin, nafamostat, octreotide, somatostatin, and ulinastatin for protection against PEP were included.

Results:

Eighty-six randomized controlled trials involving 25,246 patients were included in this network meta-analysis. Results indicated that diclofenac, GAB, GTN, indomethacin, somatostatin, and ulinastatin were more effective than placebo with odds ratios ranging between 0.48 (95% credible interval, 0.26-0.86) for GAB and 0.61 (0.39-0.94) for somatostatin. However, allopurinol, nafamostat, and octreotide showed similar efficacy as placebo in reducing the risk of PEP. No significant differences were found in the efficacy between diclofenac, GAB, GTN, indomethacin, somatostatin, and ulinastatin. In terms of prognosis, GAB may be the most effective treatment (surface under the cumulative ranking curve=70.6%) and the least effective was octreotide (surface under the cumulative ranking curve=28%).

Conclusions:

Although our analysis suggests that GAB may be the most effective drug in preventing PEP, the limitations of our study warrants more high-quality head-to-head trials of these clinical drugs in the future.
Isolated Optic Perineuritis as the Presenting Sign of Sarcoidosis
Authors: Micieli Jonathan A. , Streutker Catherine J. , McIntyre Kieran
Published: September 2019

A 35-year-old healthy African-American woman presented with a 4-month history of gradual loss of vision in the right eye from an optic neuropathy. MRI of the orbits with gadolinium showed isolated thickening and enhancement of the right optic nerve sheath. Chest x-ray and CT-scan of the chest were performed and showed bilateral hilar and mediastinal lymphadenopathy. This was suggestive of sarcoidosis, and the diagnosis was confirmed with histopathology. The patient promptly recovered vision with high-dose corticosteroids; the thickening of the optic nerve sheath also regressed. Isolated optic nerve sheath thickening from sarcoidosis is rare and may mimic compressive optic neuropathies such as optic nerve sheath meningiomas. A systemic evaluation for systemic inflammatory etiologies should be considered in such cases.
Wolbachiainfection in Argentinean populations ofAnastrepha fraterculus sp1: preliminary evidence of sex ratio distortion by one of two strains
Authors: Conte CA , Segura DF , Milla FH , Augustinos AA , Cladera JL , Bourtzis K , Lanzavecchia SL
Published: September 2019

Background

Wolbachia,one of the most abundant taxa of intracellular Alphaproteobacteria, is widespread among arthropods and filarial nematodes. The presence of these maternally inherited bacteria is associated with modifications of host fitness, including a variety of reproductive abnormalities, such as cytoplasmic incompatibility, thelytokous parthenogenesis, host feminization and male-killing.Wolbachiahas attracted much interest for its role in biological, ecological and evolutionary processes as well as for its potential use in novel and environmentally-friendly strategies for the control of insect pests and disease vectors including a major agricultural pest, the South American fruit fly,Anastrepha fraterculusWiedemann (Diptera: Tephritidae).

Results

We usedwsp,16S rRNAand a multilocus sequence typing (MLST) scheme includinggatB,coxA,hcpA,fbpA, andftsZ genes to detect and characterize theWolbachiainfection in laboratory strains and wild populations ofA. fraterculusfrom Argentina. Wolbachiawas found in allA. fraterculusindividuals studied. Nucleotide sequences analysis ofwspgene allowed the identification of twoWolbachianucleotide variants (namedwAfraCast1_A andwAfraCast2_A). After the analysis of 76 individuals, a high prevalence of thewAfraCast2_A variant was found both, in laboratory (82%) and wild populations (95%). MLST analysis identified bothWolbachiagenetic variants as sequence type 13. Phylogenetic analysis of concatenated MLST datasets clusteredwAfraCast1/2_A in the supergroup A. Paired-crossing experiments among single infected laboratory strains showed a phenotype specifically associated towAfraCast1_A that includes slight detrimental effects on larval survival, a female-biased sex ratio; suggesting the induction of male-killing phenomena, and a decreased proportion of females producing descendants that appears attributable to the lack of sperm in their spermathecae.

Conclusions

We detected and characterized at the molecular level twowspgene sequence variants ofWolbachiaboth in laboratory and wild populations ofA. fraterculus sp.1 from Argentina. Crossing experiments on singly-infectedA. fraterculusstrains showed evidence of a male killing-like mechanism potentially associated to thewAfraCast1_A -A. fraterculusinteractions. Further mating experiments including antibiotic treatments and the analysis of early and late immature stages of descendants will contribute to our understanding of the phenotypes elicited by theWolbachiavariantwAfraCast1_A inA. fraterculus sp.1.
No evidence for differences in contrast of the grey-white matter boundary in Autism Spectrum Disorders: An open replication
Authors: Traut Nicolas , Fouquet Marion , Delorme Richard , Bourgeron Thomas , Beggiato Anita , Toro Roberto
Published: September 2019

The contrast of the interface between the cortical grey matter and the white matter is emerging as an important neuroimaging biomarker for several brain disorders. Differences in grey to white matter contrast could be related to abnormalities in neuronal migration or in intra-cortical myelination, and are an appealing biomarker for ASD. Two previous studies have reported differences in contrast between patients with autism spectrum disorder and non-autistic controls.

We aimed at replicating this finding using open data from the ABIDE initiative, phases 1 and 2, gathering data from 2,148 subjects from 26 different centres and on 764 individuals from the EU-AIMS project (6 different centres). We used multiple linear regression to study the effect of the diagnosis of ASD on contrast, and 3 different strategies for controlling for multiple comparisons. We did not find statistically significant differences in the EU-AIMS dataset, and those that we found in the ABIDE dataset were due to a single centre. All the code necessary to replicate our analyses has been made available open source:https://github.com/neuroanatomy/GWPC.
Four high-quality draft genome assemblies of the marine heterotrophic nanoflagellate Cafeteria roenbergensis
Authors: Hackl Thomas , Martin Roman , Barenhoff Karina , Duponchel Sarah , Heider Dominik , Fischer Matthias G.
Published: September 2019

The heterotrophic stramenopile Cafeteria roenbergensis is a globally distributed marine bacterivorous protist. This unicellular flagellate is host to the giant DNA virus CroV and the virophage mavirus. We sequenced the genomes of four cultured C. roenbergensis strains and generated 23.53 Gb of Illumina MiSeq data (99-282 × coverage per strain) and 5.09 Gb of PacBio RSII data (13-54 × coverage). Using the Canu assembler and customized curation procedures, we obtained high-quality draft genome assemblies with a total length of 34-36 Mbp per strain and contig N50 lengths of 148 kbp to 464 kbp. The C. roenbergensis genome has a GC content of ~70%, a repeat content of ~28%, and is predicted to contain approximately 7857-8483 protein-coding genes based on a combination of de novo, homology-based and transcriptome-supported annotation. These first high-quality genome assemblies of a Bicosoecid fill an important gap in sequenced Stramenopile representatives and enable a more detailed evolutionary analysis of heterotrophic protists.
Temporal scaling in developmental gene networks by epigenetic timing control
Authors: Nguyen Phuc H.B. , Pease Nicholas A. , Ng Kenneth K.H. , Irwin Blythe , Kueh Hao Yuan
Published: September 2019

During development, progenitors follow defined temporal schedules for differentiation, to form organs and body plans with precise sizes and proportions. Across diverse contexts, these developmental schedules are encoded by autonomous timekeeping mechanisms in single cells. These autonomous timers not only operate robustly over many cell generations, but can also operate at different speeds in different species, enabling proportional scaling of temporal schedules and population sizes. By combining mathematical modeling with live-cell measurements, we elucidate the mechanism of a polycomb-based epigenetic timer, that delays activation of the T-cell commitment regulatorBcl11bto facilitate progenitor expansion. This mechanism generates activation delays that are independent of cell cycle duration, and are tunably controlled by transcription factors and epigenetic modifiers. When incorporated into regulatory gene networks, this epigenetic timer enables progenitors to set scalable temporal schedules for flexible size control. These findings illuminate how evolution may set and adjust developmental speed in multicellular organisms.
Brain functional connectivity modulates social bonding in monogamous voles
Authors: López-Gutiérrez M. Fernanda , Gracia-Tabuenca Zeus , Ortiz Juan J. , Camacho Francisco J. , Young Larry J. , Paredes Raúl G. , Diaz Nestor F. , Portillo Wendy , Alcauter Sarael
Published: September 2019

Previous studies have related pair bonding in Microtus ochrogaster, the prairie vole, with plastic changes in several brain regions. However, their socially-relevant interactions have yet to be described. In this study, we used resting state magnetic resonance imaging to explore longitudinal changes in functional connectivity of brain regions associated with pair bonding. Male and female prairie voles were scanned at baseline, after 24 hours and two weeks of cohabitation with mating. Network based statistics revealed a common network with significant longitudinal changes including prefrontal and cortical regions, the hippocampus, the anterior olfactory nucleus, the lateral septum, the paraventricular nucleus, and the ventral tegmental area.

Furthermore, baseline functional connectivity of three sub-networks predicted the onset of affiliative behavior, and a relationship was found between partner preference with long-term changes in the functional connectivity between the medial amygdala and ventral pallidum. Overall, our findings revealed the association between network-level changes and social bonding.
Population-level sensitivity to landscape variables reflects individual-based habitat selection in a woodland bat species
Authors: Jan Pierre-Loup , Zarzoso-Lacoste Diane , Fourcy Damien , Baudouin Alice , Farcy Olivier , Boireau Josselin , Le Gouar Pascaline , Puechmaille Sébastien J. , Petit Eric J.
Published: September 2019

Understanding the relationship between habitat quality and population dynamics is fundamental for long-term management and range predictions in ecology. However, habitat quality is generally only investigated at the individual scale, as it is the case for the lesser horseshoe bat (Rhinolophus hipposideros), a species of conservation concern. Using a statistical modelling approach and census data of 94 lesser horseshoe bat colonies located in Brittany (France), we analysed the effect of landscape composition and configuration on the demographic components of surveyed maternity colonies (i.e. colony size, fecundity and growth rate), and compared our result to those provided by individual-based studies. Our results validated that the landscape in a 500-meter buffer around colonies (core foraging area) is crucial for population size and dynamics, and confirmed the positive influence of broadleaved woodland proportion on bat colony size. We revealed a positive effect of lakeshores and riverbanks on colony size and growth rate, underlying the importance of these habitats for the long-term conservation of this non-migratory forest species. Importantly, our results refine previous knowledge concerning the threat posed by the intensification of human activities (e.g. urbanization, agriculture, habitat fragmentation), and highlight the negative effect of large and regular patches of artificial and crop lands and of open land patches shape complexity on all demographic variables investigated. While our results support the dependence of population dynamics and associated conservation management to individual behaviour and sensitivity, environmental responses differed between the population metrics investigated, showing that efficient range prediction will require to fully grasp the complexity of the interaction between landscape and the different population dynamic parameters.
Modeling brain dynamics after tumor resection using The Virtual Brain
Authors: Aerts Hannelore , Schirner Michael , Dhollander Thijs , Jeurissen Ben , Achten Eric , Van Roost Dirk , Ritter Petra , Marinazzo Daniele
Published: September 2019

Brain tumor patients scheduled for tumor resection often face significant uncertainty, as the outcome of neurosurgery is difficult to predict at the individual patient level. Recently, computational modeling of brain activity using so-called brain network models has been introduced as a promising tool for this purpose. However, brain network models first have to be validated, before they can be used to predict brain dynamics. In prior work, we optimized individual brain network model parameters to maximize the fit with empirical brain activity. In this study, we extend this line of research by examining the stability of fitted parameters before and after tumor resection, and compare it with baseline parameter variability using data from healthy control subjects. Based on these findings, we perform the first “virtual neurosurgery” analyses to evaluate the potential of brain network modeling in predicting brain dynamics after tumor resection.

We find that brain network model parameters are relatively stable over time in brain tumor patients who underwent tumor resection, compared with baseline variability in healthy control subjects. In addition, we identify several robust associations between individually optimized model parameters, structural network topology and cognitive performance from pre-to post-operative assessment. Concerning the virtual neurosurgery analyses, we obtain promising results in some patients, whereas the predictive accuracy of the currently applied model is poor in others. These findings reveal interesting avenues for future research, as well as important limitations that warrant further investigation.