bluuebunny/crossref_metadata_2025 huggingface dataset:
Nebulized Bacteriophages for Prophylaxis of Experimental Ventilator-Associated Pneumonia Due to Methicillin-Resistant Staphylococcus aureus
Authors: Prazak Josef , Valente Luca , Iten Manuela , Grandgirard Denis , Leib Stephen L. , Jakob Stephan M. , Haenggi Matthias , Que Yok-Ai , Cameron David R.
Published: April 2020

Objectives:

There is a need for alternative strategies to combat and prevent antibiotic-resistant bacterial infections. Here, we assessed the potential for bacteriophage prophylaxis in the context of experimental ventilator-associated pneumonia due to methicillin-resistant Staphylococcus aureus in rats.

Design:

Nebulized phages (aerophages) were delivered to the lungs of rats using a modified vibrating mesh aerosol drug delivery system. Animals were intubated and ventilated for 4 hours, at which point they were infected with methicillin-resistant S. aureus strain AW7 via the endotracheal tube, extubated, and then monitored for 96 hours.

Setting:

Ventilator-associated pneumonia.

Subjects:

Male Wistar rats.

Interventions:

A single application of aerophages prior to ventilation at one of two concentrations (~1010 plaque forming units/mL or ~1011 plaque forming units/mL).

Measurements and Main Results:

1) Animal survival at 96 hours, 2) enumeration of bacteria and phages in the lungs and spleen, and 3) lung tissue histopathology. Animals that received aerophages prior to ventilation and methicillin-resistant S. aureus challenge showed a higher survival rate compared with untreated controls (60% for animals that received 3 × 1010 plaque forming units; 70% for animals that received 3 × 1011 plaque forming units; 0% for controls; p < 0.01 for each treatment versus untreated). Surviving animals that received aerophage prophylaxis had fewer methicillin-resistant S. aureus in the lungs compared with untreated control animals that succumbed to pneumonia (1.6 × 106 colony forming units/g vs 8.0 × 108; p < 0.01).

Conclusions:

Prophylactically administered nebulized bacteriophages reduced lung bacterial burdens and improved survival of methicillin-resistant S. aureus infected rats, underscoring its potential in the context of ventilator-associated pneumonia.
Association of cardiovascular diseases with milk intake among general Chinese adults
Authors: Wang Xin-Yan , Liu Fang-Chao , Yang Xue-Li , Li Jian-Xin , Cao Jie , Lu Xiang-Feng , Huang Jian-Feng , Li Ying , Chen Ji-Chun , Zhao Lian-Cheng , Shen Chong , Hu Dong-Sheng , Zhao Ying-Xin , Yu Ling , Liu Xiao-Qing , Wu Xian-Ping , Gu Dong-Feng
Published: April 2020

Background:

The association of milk intake with cardiovascular disease (CVD) and cause-specific mortality remained controversial and evidence among the Chinese population was limited. We aimed to study the relationship between milk intake and CVDs among general Chinese adults.

Methods:

A total of 104,957 participants received questionnaire survey. Results of physical examination such as anthropometric measurements and biochemical tests during 2007 to 2008, demographic data and their information on milk intake were collected through standardized questionnaires. Cox proportional hazard regression models were used to calculate hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) of CVD incidence, cause-specific mortality and all-cause mortality related to milk intake. Restricted cubic splines (RCSs) were applied to examine dose-response associations.

Results:

Among the 91,757 participants with a median follow-up period of 5.8 years, we documented 3877 CVD cases and 4091 all-cause deaths. Compared with participants who never consumed milk, the multivariate-adjusted HRs (95% CIs) of CVD incidence for 1 to 150 g/day, 151 to 299 g/day, and ≥300 g/day were 0.94 (0.86–1.03) (P > 0.05), 0.77 (0.66–0.89) (P < 0.05), and 0.59 (0.40–0.89) (P < 0.05), respectively; each 100 g increase of daily milk intake was associated with 11% lower risk of CVD incidence (HR, 0.89; 95% CI: 0.85–0.94; P < 0.001), and 11% lower risk of CVD mortality (HR, 0.89; 95% CI: 0.82–0.97; P = 0.008) after adjustment for age, sex, residential area, geographic region, education level, family history of CVD, smoking, alcohol drinking, physical activity level, body mass index, and healthy diet status (ideal or not). RCS analyses also showed a linear dose-response relationship with CVD (P for overall significance of the curve <0.001; P for non-linearity = 0.979; P for linearity <0.001) and stroke (P for overall significance of the curve = 0.010; P for non-linearity = 0.998; P for linearity = 0.002) incidence, and CVD mortality (P for overall significance of the curve = 0.045; P for non-linearity = 0.768; P for linearity = 0.014) within the current range of daily milk intake.

Conclusions:

Daily milk intake was associated with lower risk of CVD incidence and mortality in a linear inverse relationship. The findings provide new evidence for dietary recommendations in CVD prevention among Chinese adults and people with similar dietary pattern in other countries.
Tacrolimus and ascomycin inhibit melanoma cell growth, migration and invasion via targeting nuclear factor of activated T-cell 3
Authors: Xiao Tian , Chen Wencong , Wang Shuangfeng , Huang Shiying , Chiang Chengyao , Zou Yongdong , Zhao Yongxiang , Zheng Duo
Published: April 2020

Melanoma is the most malignant form of skin cancer with high metastatic potential. Nuclear factor of activated T-cells (NFATs) are discovered as transcription factors that regulate the expression of proinflammatory cytokines and other genes during the immune response. Among five NFAT members, NFAT3 is exclusively not expressed in immune cells and its role in progression of different types of cancer remains controversial. Our previous study showed that NFAT3 was highly expressed in skin cancer compared with normal skin tissues and critical for melanoma cell survival and tumor growth. Here, we reported that knockdown of NFAT3 expression, as well as treatment with the calcineurin (CaN) inhibitors, tacrolimus (FK506) or ascomycin (FK520) inhibits melanoma cell migration and invasion, and also proliferation and colony formation. Mechanistic studies revealed that FK506 or FK520 blocked the nuclear translocation and reduced the transcriptional activity of NFAT3. These data support that the antimelanoma effect of FK506 and FK520 is partially mediated by inhibiting the oncogenic factor NFAT3, suggesting that therapeutics based on NFAT3 inhibition may be effective in clinical melanoma treatment.
Interpretation of Physiologic and Left Ventricular Assist Device Parameters: Implications for Physical Therapist Decision-Making
Authors: Shoemaker Michael J. , Veldman Sarah , Van Dam Ashley , Wainscott Teresa L.
Published: April 2020

As members of the interprofessional team caring for patients with left ventricular assist devices (LVADs), physical therapists need to be able to interpret whether a response to intervention is appropriate and anticipate the impact of changes of medical management to ensure adequate cardiac output to meet task demands, prevent syncope, and prevent suction events. This requires that physical therapist base decision-making on foundational physiologic and pathophysiologic principles and the way in which they are modified by the presence of an LVAD. Unfortunately, the product manuals in use for the most common LVADs do not address interpretation of mobility- and exercise-related LVAD and physiologic parameter changes. Numerous studies exist regarding LVAD and physiologic parameter changes with cardiopulmonary exercise testing, but none provide a singular framework that can be easily referenced by physical therapists to assist in mobilization- and intervention-related decision-making. The present clinical perspective therefore summarizes and synthesizes key concepts regarding interpretation of mobility- and exercise-related LVAD and physiologic parameter changes to help inform physical therapist clinical decision-making across the continuum of care.
Cis-acting regulatory elements regulating CYP3A4 transcription in human liver
Authors: Collins Joseph M. , Wang Danxin
Published: April 2020

The CYP3A4 enzyme is the most abundant drug-metabolizing enzyme in the liver, metabolizing ~50% of commonly used medications. CYP3A4 displays large interperson variability in expression and enzyme activity with unknown causes. This study aims to identify cis-acting regulatory elements controlling the transcription of CYP3A4, using chromatin conformation capture (4C and 3C assays), chromatin immunoprecipitation followed by quantitative PCR (ChIP-qPCR), clustered regularly interspaced short palindromic repeats (CRISPR)-mediated deletions of genomic regions and reporter gene assays in primary culture human hepatocytes and hepatic cell lines. 4C assays identified four regions (R1–R4) interacting with the CYP3A4 promoter, one of which overlaps with the previously identified upstream enhancers CLEM4/XREM (R2) while the other three are novel. ChIP-qPCR, reporter gene assays and CRISPR-mediated deletion experiments indicate regulatory roles for both R2 and R4. Interestingly, the deletion of R4 increased CYP3A4 while decreasing CYP3A43 expression, possibly due to competitive domain–domain interactions within the CYP3A cluster, supported by deletion of R4 increasing interaction between the CYP3A4 promoter and R2. We also identified a single nucleotide polymorphism rs62471956 within R4, with the variant allele A having increased transcriptional activity in a reporter gene assay. The rs62471956 A allele is associated with higher CYP3A43 expression and lower CYP3A4 expression in a cohort of 136 liver samples, further supporting the opposing effects of R4 on CYP3A4 and CYP3A43. rs62471956 is in complete linkage disequilibrium with CYP3A4*22, potentially contributing to reduced expression of CYP3A4*22. These results validate previously identified enhancers (CLEM4 and XREM) of CYP3A4 and demonstrate additional regulatory mechanisms underlying CYP3A4 transcriptional control via competitive domain–domain interactions within the CYP3A cluster.
Cervicovaginal lavage fluid zinc level as a marker of vaginal atrophy
Authors: Damjanovich Peter , Sipos Attila Gergely , Larson Kindra , Cunningham Tina D. , Takacs Peter , Kozma Bence
Published: April 2020

Objectives:

This study aimed to investigate the correlation between cervicovaginal fluid zinc levels and participants’ menopausal status and the presence of vulvovaginal symptoms of genitourinary syndrome of menopause.

Methods:

Women included in the study underwent a pelvic examination, collection of vaginal cytology, and cervicovaginal lavage was performed in a standardized fashion. The cervicovaginal lavage zinc content was determined. The vaginal health index was calculated, and the visual analog scale was obtained based on the participant's burning, itching, vaginal pain, dyspareunia, dryness, and dysuria.

Results:

One hundred twenty women participated in the study. Eighty-two participants were menopausal. The mean vaginal health index was 15 ± 6, while the total visual analog scale score was 14 ± 14. We found significant differences between cervicovaginal lavage zinc level and age group, menopausal status, presence of vaginal dryness, and vaginal atrophy. We also found a moderate positive correlation between Vaginal Maturation Value and cervicovaginal lavage zinc levels (r = 0.495, P value < 0.01) in the correlation analysis. However, in the multivariate regression model, including all significant factors, only vaginal atrophy remained significant.

Conclusions:

We found a significant association between vaginal atrophy (vaginal maturation value < 50) and cervicovaginal lavage zinc levels. Zinc levels of cervicovaginal lavage could be used as a new marker of vaginal atrophy.

Video Summary:
http://links.lww.com/MENO/A575.
Effect of Chinese herbal medicine on serum lipids in postmenopausal women with mild dyslipidemia: a randomized, placebo-controlled clinical trial
Authors: Nie Guangning , Yang Hongyan , Liu Jian , Cao Xiaojing , Cheng Fangping , Du Qiaolin , Wang Xiaoyun
Published: April 2020

Objective:

Previous studies have shown the association between menopause and dyslipidemia. This study was aimed to evaluate the effect of Chinese herbal medicine, tonifying kidney and descending turbidity (TKDT) granule, on serum lipid profiles in postmenopausal women with dyslipidemia.

Methods:

A double-blind randomized, placebo-controlled trial was conducted among 104 postmenopausal Chinese women with mild dyslipidemia. Participants were randomized into treatment group (n = 53) and control group (n = 51). The participants in the treatment group received TKDT granule once per day for 24 weeks, whereas the control group received placebo in the same manner. All participants were subjected to healthy lifestyle during the study. Serum lipid profiles, body weight, waist circumference, and safety indicators were measured both at baseline and 24 weeks after admission.

Results:

Compared with placebo, significant improvements in total cholesterol, low-density lipoprotein cholesterol, apolipoprotein-B (Apo-B), weight, and waist circumference in the TKDT group (P < 0.05) were observed after 24 weeks of treatment. Total cholesterol, low-density lipoprotein cholesterol, and Apo-B were decreased by 0.84 (0.77) mmol/L, 0.72 (0.77) mmol/L, and 0.12 (0.27) mmol/L, mean ± SD respectively. The weight, waist circumference, and body mass index were decreased by 4.07 (3.01) kg, 3.10 (2.95) cm, 1.60 (1.13), respectively. There were no significant differences in triglycerides, high-density lipoprotein cholesterol, and Apo-A between the two groups. Seven participants in the treatment group and six participants in the placebo group had mild or moderate adverse reactions.

Conclusion:

TKDT granule improved the lipid profile and reduced the related metabolic abnormalities in postmenopausal women with mild dyslipidemia based on lifestyle changes.
E-cigarette “Vape” Device Explosion Causing C Spine Fracture
Authors: Hagarty Sarah , Luo Jessica
Published: April 2020

Summary: Electronic cigarette (e-cigarette) use has grown exponentially since its introduction to the US market in 2007.1 Sales went largely unregulated until 2016, when the Food and Drug Administration expanded tobacco laws to encompass the manufacturing, distribution, and marketing of e-cigarette products.2
,
3 Production safety standards are still being established. Rechargeable lithium batteries used have been reported to combust. The US Fire Administration reported 195 cases of e-cigarette explosions and fires from 2009 to 2016. The proximity of the explosions can cause serious burns and facial trauma to the user.3
,
4 We present a case report of a 30-year-old woman with oral soft tissue and dental injuries, C1 fracture, and left vertebral artery dissection from an e-cigarette explosion.
Narrative-Based Practice
Authors: Burrai Francesco , Mettifogo Mariangela , Micheluzzi Valentina , Ferreira Flavia Emanuela , Pinna Leonardo , Magavern Emma Forton
Published: April 2020

Narrative-based practice has been developed to bring the health care aspects of illness and treatment closer to the psychosocial and life experiences of a patient. It gives value to the lived experience by using writing tools, spoken words, poetry, drawing, and photography. Nephrology has become one of the first health care fields, likely due to its large patient burden of both critical and chronic disease, to use narrative-based practice. The use of narrative-based practice in renal care explores the lived experience through structured and semistructured interviews with patients, caregivers, and health care providers. The principle topics discussed are the lack of a “disease identity” that would allow patients to identify themselves with a specific state of illness, the “uncertainty” of living with an illness characterized by continuous progression and regression, and the living with the “unspeakable” looming specter of death. This review highlights the powerful significance of qualitative knowledge gained with the narrative method. Increased awareness of these aspects of patients' lived experiences can help nurses improve the quality and effectiveness of the therapeutic relationship between patient and health care professional and may offer a promising approach, within this relationship, to decreasing patient feelings of isolation.
Diagnostic Performance of 68Ga-PSMA-11 Positron-emission-tomography/Computed-tomography in a Large Cohort of Patients with Biochemical Recurrence of Prostate Carcinoma
Authors: Hoffmann Manuela A. , Buchholz Hans-Georg , Wieler Helmut J. , Müller-Hübenthal Jonas , Trampert Ludwin , Richardsen Ines , Schreckenberger Mathias
Published: April 2020

Gallium-68 (68Ga) prostate-specific-membrane-antigen positron-emission-tomography/computed-tomography is a highly promising method for imaging primary and recurrent prostate cancer. These dual-modality imaging technologies enable whole-body functional and anatomical evaluation in a single session. This study investigated the performance of 68Ga-prostate-specific-membrane-antigen-11 positron-emission-tomography/computed-tomography for detecting prostate carcinoma in patients with rising prostate-specific-antigen after primary therapy. Six hundred sixty (660) patients with biochemical recurrence referred for positron-emission-tomography/computed-tomography with 68Ga-prostate-specific-membrane-antigen-11 were evaluated retrospectively. Prostate-specific-antigen-stratified cohorts of pathological scan results were analyzed, and relationships between prostate-specific-antigen kinetics and PSMA-positive tumor lesions were correlated. Gallium-68 prostate-specific-membrane-antigen-11 positron-emission-tomography/computed-tomography showed a pathological prostate-specific-membrane-antigen uptake in 76% (500 of 660 patients). Positive scans were positively associated with prostate-specific-antigen (p<0.001). For patients with prostate-specific-antigen <0.2 ng mL−1, the PSMA-positive tumor lesions rate was 41%. Patients with prostate-specific-antigen of 0.2–<0.5 ng mL−1, 0.5–<1.0 ng mL−1, 1.0–<2.0 ng mL−1, and 2.0–<5.0 ng mL−1 showed rates of 44.7%, 61.7%, 72.3%, 85.2%, respectively, and for prostate-specific-antigen of ≥5.0 ng mL−1 it increased to 94%. Prostate-specific-antigen velocity was also correlated with PSMA-positive tumor lesions (p<0.001). In contrast, no association was found for prostate-specific-antigen doubling time (p=0.74). PSMA-positive tumor lesions were significantly increased in patients with primary intermediate- (Gleason Score7) and high-risk (Gleason Score>7) vs. low-risk prostate cancer (Gleason Score<7) (p<0.001). Our data confirm the high performance of 68Ga-prostate-specific-membrane-antigen positron-emission-tomography/computed-tomography for the detection of recurrent prostate cancer. This may alter treatment planning and has been documented in other studies as well.
Corneal Biomechanical Changes After Uneventful Phacoemulsification in Patients With Type 2 Diabetes Mellitus and Patients Without Diabetes
Authors: Beato João N. , Esteves-Leandro João , Reis David , Falcão Manuel , Rosas Vítor , Carneiro Ângela , Falcão Reis Fernando
Published: April 2020

Purpose:

To compare corneal biomechanical changes after uneventful phacoemulsification cataract surgery between type 2 diabetic (DM) and nondiabetic patients.

Methods:

Forty-four diabetic (44 eyes) and 44 (44 eyes) age and sex-matched non-DM controls with age-related cataract were enrolled in this prospective observational study. Corneal hysteresis (CH), corneal resistance factor (CRF), and corneal-compensated intraocular pressure (IOPcc) were evaluated by using the ocular response analyzer; central corneal thickness was recorded by using the Pentacam HR. Patients were evaluated preoperatively and 1 and 6 months after surgery.

Results:

In the DM group, CH was observed to be significantly lower than preoperative value (9.8 ± 1.5 mm Hg) at 1 month (9.4 ± 1.2 mm Hg, P = 0.040), but not at the 6-month follow-up (9.6 ± 1.6 mm Hg, P = 0.437),whereas it did not change significantly in the non-DM group (preoperative 9.8 ± 1.3 mm Hg vs. 1 month 9.6 ± 1.1 mm Hg vs. 6 months 10.1 ± 1.1 mm Hg, P > 0.05). CRF was significantly lower than the preoperative values at 1 and 6 months in both groups (P ≤ 0.001). Postoperative CH change was significantly associated with preoperative CH (P < 0.001), preoperative IOPcc (P = 0.004), and IOPcc change (P < 0.001), whereas CRF change was only correlated with preoperative CRF (P < 0.001). There was a significant postoperative IOPcc reduction 6 months after surgery (P < 0.001) in both DM and non-DM groups; however, central corneal thickness was not found to significantly change in the postoperative period (P > 0.05).

Conclusions:

This study showed that phacoemulsification causes a significant and persistent decrease in intraocular pressure and CRF in both groups, whereas CH recovered to preoperative values, although more slowly in patients with diabetes.
Outcomes of Ipsilateral Simple Limbal Epithelial Transplantation, Tenonectomy, Mitomycin and Amniotic Membrane Transplantation for Treatment of Recurrent Pterygium
Authors: Trinh Tanya , Mimouni Michael , Mednick Zale , Einan-Lifshitz Adi , Cohen Eyal , Santaella Gisella , Sorkin Nir , Slomovic Allan
Published: April 2020

Purpose:

To report on the outcomes of recurrent pterygium treated by ipsilateral simple limbal epithelial transplantation (SLET), mitomycin, tenonectomy, and amniotic membrane transplantation.

Methods:

A retrospective, interventional study was conducted including all patients with recurrent pterygium who underwent SLET surgery under a single surgeon using ipsilateral donor tissue with a minimum 6-month follow-up at Toronto Western Hospital, Canada. Outcome measures included the following: recurrence rates, best spectacle–corrected visual acuity, and postoperative complications.

Results:

Ten eyes of 10 patients, aged 60.7 ± 18.5 years (range 23–79) with a mean follow-up time of 15.2 ± 10.0 months of which 50% (n = 5) were men, were included. Eight eyes (80%) had a history of 2 or less pterygium operations. Two patients had 3 and 5 previous pterygium operations, respectively. Concurrent limbal stem cell disease was noted in 6 eyes (60%). Average number of pterygium recurrences per eye was 1.9 ± 1.3 (range 1–5). Mean pre-op best-corrected visual acuity was 0.5 LogMAR (Snellen equivalent 20/60, range 20/20 to counting fingers). Best-corrected visual acuity remained the same or improved in 6 eyes (60%). Recurrence was noted in 1 eye (10%) with a history of 5 previous pterygium excisions and remained stable at the last follow-up. No patients required a second operation.

Conclusions:

Ipsilateral SLET with mitomycin, tenonectomy, and amniotic membrane transplantation is a novel technique to address recurrent pterygium. Concurrent limbal stem cell diseases are often present. Initial results demonstrate low recurrence. Visual improvement is modest. Stabilization of the ocular surface to improve vision is possible.
Adverse Events Following Immunization Among Children With Epilepsy
Authors: Top Karina A. , Righolt Christiaan H. , Hawken Steven , Donelle Jessy , Pabla Gurpreet , Brna Paula , Deeks Shelley L. , Smith Bruce , Wilson Kumanan , Mahmud Salaheddin M.
Published: April 2020

Background:

In children with epilepsy, fever and illness are known triggers for seizure; therefore, clinicians and parents could be concerned that immunization-induced inflammation and fever could also trigger seizures. We sought to estimate the risk of emergency department (ED) visit or hospitalization for epilepsy/seizure and all causes after immunization in children younger than 7 years of age with epilepsy.

Methods:

We conducted a self-controlled case series of children diagnosed with epilepsy before their 7th birthday and immunized from 2005 to 2015 in Ontario (population 14.2 million) and Manitoba (population 1.3 million), Canada, using administrative healthcare data. We estimated the age- and season-adjusted relative incidence (aRI) of epilepsy/seizure-related and all-cause ED visits/hospitalizations during various risk periods 0–28 days after inactivated and live immunizations versus a control period 35–83 days postimmunization. Estimates from each province were analyzed separately and then combined in a random-effects meta-analysis.

Results:

The combined risk of epilepsy/seizure-related hospitalization/ED visit was increased 0–2 days after inactivated vaccines (aRI = 1.5, 95% confidence interval: 1.1–1.9) and 7–10 days after live vaccines (aRI = 1.9, 1.4–2.7). For all-cause ED visit/hospitalization, the combined aRI estimate was 0.9 (0.8–1.2) 0–2 days after inactivated vaccines and 1.3 (1.1–1.5) 7–10 days after live vaccines.

Conclusions:

The risk of epilepsy/seizure-related ED visit/hospitalization was modestly increased among children with epilepsy during peak periods of fever and inflammation following inactivated and live vaccines. These risks must be balanced against the risk of complications from vaccine-preventable diseases.
Reduced Antibiotic Exposure by Serial Physical Examinations in Term Neonates at Risk of Early-onset Sepsis
Authors: Vatne Anlaug , Klingenberg Claus , Øymar Knut , Rønnestad Arild E , Manzoni Paolo , Rettedal Siren
Published: April 2020

Background:

Suspected early-onset sepsis (EOS) results in antibiotic treatment of a substantial number of neonates who are uninfected. We evaluated if an approach using serial physical examinations (SPEs) can reduce antibiotic exposure for suspected EOS in term neonates during the first 3 days of life, without affecting safety.

Methods:

Within a quality-improvement framework, SPEs for 24–48 hours for neonates with suspected EOS was implemented in the neonatal intensive care unit, Stavanger, Norway. The proportion of neonates ≥37 weeks gestation exposed to antibiotics, antibiotic therapy-days and the safety outcome time from birth to start antibiotics were compared between a baseline period (April 2014–February 2016), when a risk factor based approach was used, and a post-SPE-implementation period (January 2017–November 2018).

Results:

We included all term live born neonates (n = 17,242) in the 2 periods. There was a 57% relative reduction in neonates exposed to antibiotics; 2.9% in the baseline and 1.3% in the post-implementation period, P < 0.001. There was a 60% relative reduction in mean antibiotic therapy-days/1000 patient-days; from 320 to 129, P < 0.001, and a 50% relative reduction in time to initiate antibiotics in suspected EOS-cases, from median (interquartile range) 14 (5–28) to 7 (3–17) hours, P = 0.003. The incidence of culture-positive EOS remained unchanged. There were no infection-attributable deaths.

Conclusions:

Implementing SPE to guide empiric antibiotic therapy in term neonates with suspected EOS more than halved the burden of antibiotic exposure, without delay of antibiotic treatment of infected neonates or increased sepsis-related mortality.
Advances in Interventional Endoscopic Ultrasound (EUS)
Authors: Simons-Linares Carlos Roberto , Chahal Prabhleen
Published: April 2020

Endoscopic ultrasound (EUS) has become the therapeutic intervention of choice for multiple diseases and continues to evolve rapidly. Its increasing use has allowed the development and adaptation of multiple, revolutionary devices and tools. Currently, there is paucity of randomized clinical trials evaluating multiple EUS-guided interventions and the vast majority of published data is heterogenous. However, the available literature on EUS-guided therapeutic interventions continues to expand and demonstrate its safety, efficacy and cost effectiveness in carefully selected patients when performed by expert endosonographers. The future of interventional EUS appears to be bright!
Torsion in the Gravid and Nongravid Uterus: A Review of the Literature of an Uncommon Diagnosis
Authors: Ramseyer Abigail M. , Whittington Julie R. , Resendez Victoria A. , Whitcombe Dayna D. , Magann Everett F.
Published: April 2020

Importance

Uterine torsion is an uncommon but life-threatening clinical situation that requires a high index of suspicion for diagnosis.

Objective

The aim of this study was to review literature and determine the etiology, presentation, diagnosis, and management of uterine torsion in the gravid and nongravid patients.

Evidence Acquisition

A literature search was undertaken by our research librarian using the search engines PubMed and CINAHL. The search terms used were “uterine torsion” OR (uterus and torsion). The search was limited to the English language, but the years searched were unlimited.

Results

The search identified 177 articles, 91 of which are the basis for this review. There have been 41 cases or gravid uterine torsion, their characteristics, and symptoms published since 2006. Torsion is rare in nongravid patients, but can still occur.

Conclusion and Relevance

Uterine torsion is rare, can affect all ages, and can have significant implications for women. Prompt recognition allows for timely intervention and can mitigate harm.

Target Audience

Obstetricians and gynecologists, family physicians.

Learning Objectives

After completing this activity, the learner should be better able to diagnose uterine torsion in the gravid and nongravid uteri and identify causative factors if present; ascertain differences in uterine torsion presentation in gravid and nongravid patients; identify severity of symptoms from asymptomatic to acute; and implement a treatment plan based on the reduction of morbidity and mortality while considering fertility preservation.
Intraoperative Assessment of DIEP Flap Breast Reconstruction Using Indocyanine Green Angiography: Reduction of Fat Necrosis, Resection Volumes, and Postoperative Surveillance
Authors: Hembd Austin S. , Yan Jingsheng , Zhu Hong , Haddock Nicholas T. , Teotia Sumeet S.
Published: April 2020

Background:

This study aims to characterize the effect of laser-assisted indocyanine green fluorescence angiography on fat necrosis and flap failure in deep inferior epigastric artery perforator (DIEP) flap breast reconstruction.

Methods:

A retrospective review was performed on 1000 free flaps for breast reconstruction at a single center from 2010 to 2017. Indocyanine green angiography was used after completion of recipient-site anastomoses to subjectively assess for areas of hypoperfusion. A multivariable logistical analysis was conducted with 24 demographic and surgical factors and their effects on fat necrosis and flap failure.

Results:

Five hundred six DIEP flaps were included in the statistical analyses. Thirteen percent of flaps had fat necrosis. Indocyanine green angiography was used for 200 flaps and was independently associated with a decrease in the odds of fat necrosis (OR, 0.38; p = 0.004). There was no reduction in flap failure rates when using indocyanine green angiography (OR, 1.15; p = 0.85). However, there was a decrease in flap loss with increasing venous coupler diameter (OR, 0.031 per 1-mm increase; p = 0.012). The 84.9-g higher weight of resected tissue before inset without indocyanine green angiography versus the weight of the tissue resected with indocyanine green angiography was statistically significant (p = 0.01). Per single incident of fat necrosis, our cohort underwent an additional 0.69 revision procedures, 1.22 imaging studies, 0.77 biopsies, and 1.7 additional oncologic office visits.

Conclusion:

Intraoperative indocyanine green fluorescence angiography decreases the odds of fat necrosis, saves volume when flap trimming at inset, and can significantly reduce the postoperative surveillance burden in DIEP-based breast reconstruction.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
Dipeptidyl Peptidase-4 Inhibitor Reduces the Risk of Developing Hypertrophic Scars and Keloids following Median Sternotomy in Diabetic Patients: A Nationwide Retrospective Cohort Study Using the National Database of Health Insurance Claims of Japan
Authors: Suwanai Hirotsugu , Watanabe Ryo , Sato Munemori , Odawara Masato , Matsumura Hajime
Published: April 2020

Background:

Hypertrophic scars and keloids, which are abnormalities of fibrosis, often occur in surgical wounds; however, their exact cause and preventive measures are unknown. The administration of dipeptidyl peptidase-4 inhibitors to humans is expected to suppress fibrosis in wounds and minimize hypertrophic scar and keloid formation.

Methods:

This study aimed to verify the suppressive effect of dipeptidyl peptidase-4 inhibitors on the formation of hypertrophic scars or keloids using real world data from the National Database of Health Insurance Claims and Specific Health Checkups of Japan. It is a retrospective cohort study, and data were extracted from the National Database between April of 2013 and March of 2015. Patients who underwent median sternotomy were included in the study based on their claimed surgical codes. Subjects who were prescribed dipeptidyl peptidase-4 inhibitors constituted the treatment group; subjects who were not prescribed or administered dipeptidyl peptidase-4 inhibitors during that period constituted the nontreatment group.

Results:

Subjects included 5430 patients throughout Japan (3509 men and 1921 women). Of the 446 subjects who were treated with dipeptidyl peptidase-4 inhibitors within 1 year before the procedure, fewer than 10 (<2 percent) developed either hypertrophic scars or keloids. Of the 4984 subjects who were not treated, 152 (3.05 percent) were at significantly lower risk for hypertrophic scars and keloids (p = 0.04). A logistic regression analysis was performed to adjust for confounding factors, with history of hypertrophic scar formation as the explained variable.

Conclusion:

This study revealed that dipeptidyl peptidase-4 inhibitors suppress the onset of hypertrophic scars or keloids after surgery in humans.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
Recurrence in Patients Achieving Pathological Complete Response After Neoadjuvant Treatment for Advanced Pancreatic Cancer
Authors: Blair Alex B. , Yin Ling-Di , Pu Ning , Yu Jun , Groot Vincent P. , Rozich Noah S. , Javed Ammar A. , Zheng Lei , Cameron John L. , Burkhart Richard A. , Weiss Matthew J. , Wolfgang Christopher L. , He Jin
Published: April 2020

Objective:

The aim of this study was to characterize the patterns and treatment of disease recurrence in patients achieving a pathological complete response (pCR) following neoadjuvant chemoradiation for advanced pancreatic ductal adenocarcinoma (PDAC).

Summary of Background Data:

A pCR is an independent predictor for improved survival in PDAC. However, disease recurrence is still observed in these patients.

Methods:

Patients with advanced PDAC who were treated with neoadjuvant therapy and had a pCR were identified between 2009 and 2017. Overall survival (OS) was determined from the initiation of neoadjuvant, disease-free survival (DFS) from the date of surgery, and post-recurrence survival (PRS) from the date of recurrence. Factors associated with recurrence were analyzed using a Cox-regression model.

Results:

Of 331 patients with borderline resectable or locally advanced PDAC, 30 achieved a pCR following neoadjuvant treatment and pancreatectomy. The median DFS for pCR patients was 29 months and OS 76 months. Recurrence was observed in 14 patients. No clinicopathologic or treatment characteristics were associated with survival. The median PRS following recurrence was 25 months. Treatment following recurrence included chemotherapy, radiation or ablation, and surgical resection. Hepatectomy or completion pancreatectomy was accomplished in 2 patients that remain alive 13 and 62 months, respectively, following metastasectomy.

Conclusions:

A pCR following neoadjuvant therapy in patients with advanced PDAC is associated with remarkable survival, although recurrence occurs in about half of patients. Nevertheless, patients with pCR and recurrence respond well to treatment and survival remains encouraging. Advanced molecular characterization and longitudinal liquid biopsy may offer additional assistance with understanding tumor biologic behavior after achieving a pCR.
Does Obtaining a Diagnosis of Interstitial Cystitis/Bladder Pain Syndrome Improve Symptoms or Quality of Life? A Cross-sectional Questionnaire-Based Study
Authors: Volpe Katherine A. , Mandelbaum Rachel , Rodriguez Larissa V. , Özel Begüm Z. , Rolston Renee , Dancz Christina E.
Published: April 2020

Objectives

The aim of this study was to investigate whether receiving a clinical diagnosis of interstitial cystitis (IC) or bladder pain syndrome (BPS) improves patients’ symptoms, health-related quality of life (HRQOL), or ability to cope with their symptoms.

Methods

In this cross-sectional study, participants with self-reported IC/BPS completed an online questionnaire recalling their perceived change in symptoms after diagnosis and treatment. The questionnaire included demographic information, overall HRQOL measured on a visual analog scale (VAS), O’Leary-Sant Interstitial Cystitis Problem Index, the Urinary Impact Questionnaire, and questions regarding patient beliefs about diagnosis. HRQOL and symptom impact scales were compared before and after diagnosis and treatment. Demographic data, symptom data, and beliefs were examined for correlation with improvement in quality of life after diagnosis.

Results

A total of 1052 participants initiated the survey and were included in the analysis; most of them identified as female, non-Hispanic, and white (90%). Before symptom onset, median VAS HRQOL score was 87 (interquartile range [IQR], 77–95). Median scores nadired at 34 (IQR, 20–59) after symptom onset before diagnosis, but improved to 61 after diagnosis and treatment (IQR, 38–74; all P < 0.001). Scores remained stable after diagnosis and initiation of treatment with a median score of 65 at the time of survey (IQR, 37–80; P > 0.05). Age, insurance type, and improvement in scores on the symptom impact scale predicted improvement in HRQOL after diagnosis and treatment in the multivariable model.

Conclusions

Participants reported improvements on global and symptom-specific quality of life measures after diagnosis and treatment for IC/BPS.
Effectiveness of Botulinum Toxin for Treatment of Symptomatic Pelvic Floor Myofascial Pain in Women: A Systematic Review and Meta-analysis
Authors: Meister Melanie R. , Brubaker Allison , Sutcliffe Siobhan , Lowder Jerry L.
Published: April 2020

Objectives

The aims of the study were to systematically review the literature and to synthesize the evidence for the effectiveness of botulinum toxin injection to the pelvic floor muscles for treating pelvic floor myofascial pain in female patients.

Methods

This systematic literature search was performed in February 2018 and updated in September 2019. Articles were screened based on predefined criteria: (1) adult population, (2) female patients, (3) treatment of pelvic pain by transvaginal botulinum toxin injection into the pelvic floor, (4) published in English or English translation available, (5) study design including randomized controlled trials, cohort studies, and case series with more than 10 participants, and (6) quantitative report of pain scores. Nine studies were included in the primary analysis, and an unpublished study was included in a sensitivity analysis. A random effects model with robust variance estimation was used to estimate the pooled mean difference in patient-reported pain scores after botulinum toxin injection.

Results

A statistically significant reduction in patient-reported pain scores was noted at 6 weeks after botulinum toxin injection (mean difference, 20.3; 95% confidence interval, 11.7–28.9) and continued past 12 weeks (mean difference, 19.4; 95% confidence interval, 14.6–24.2). Significant improvement was noted in secondary outcomes including dyspareunia, dyschezia, and quality of life.

Conclusions

This systematic review and meta-analysis support the conduct of future, large-scale randomized controlled trials to determine the efficacy and optimize administration of botulinum toxin injections for treatment of pelvic floor myofascial pain and associated symptoms in women.
Liver Transplantation in Patients With Pretransplant Aspergillus Colonization: Is It Safe to Proceed?
Authors: Amin Arpit , Molina Alfonso , Quach Lisa , Ito Takahiro , McMillan Robert , DiNorcia Joseph , Agopian Vatche G. , Kaldas Fady M. , Farmer Douglas G. , Busuttil Ronald W. , Winston Drew J.
Published: April 2020

Background.

Patients with end-stage liver disease and pretransplant Aspergillus colonization are problematic for determining liver transplant candidacy and timing of transplantation because of concerns for posttransplant invasive aspergillosis.

Methods.

We performed a retrospective review of the medical and laboratory records of all adult patients (aged ≥18 y) who underwent liver transplantation with pretransplant Aspergillus colonization at the Ronald Reagan University of California, Los Angeles, Medical Center from January 1, 2010, to December 31, 2015.

Results.

A total of 27 patients who had Aspergillus colonization (respiratory tract 26, biliary tract 1) before liver transplantation were identified. Pretransplant characteristics included previous liver transplant (11 of 27, 40.7%), dialysis (22 of 27, 81.5%), corticosteroid therapy (12 of 27, 44.4%), intensive care unit stay (27 of 27, 100%), and median model for end-stage liver disease score of 39. Only 22.2% (6 of 27) received pretransplant antifungal agents (median duration, 5 d), whereas 100% (27 of 27) received posttransplant antifungal prophylaxis (voriconazole 81.4%, 22 of 27; echinocandin 14.8%, 4 of 27; voriconazole plus echinocandin 3.7%, 1 of 27) for median duration of 85 d. Posttransplant invasive fungal infection occurred in 14.8% (4 of 27; aspergillosis 3, mucormycosis 1). Both 6-month and 12-month survival were 66.7% (18 of 27), but only 1 death was due to fungal infection. Other causes of death were liver graft failure, intraabdominal complications, and malignancy.

Conclusions.

A substantial number of patients with pretransplant Aspergillus colonization can still undergo successful liver transplantation if they are otherwise suitable candidates and receive appropriate antifungal prophylaxis. Posttransplant outcome in these patients is determined mostly by noninfectious complications and not fungal infection. Pretransplant Aspergillus colonization alone should not necessarily preclude or delay liver transplantation.
Effect of ketamine on voltage-gated potassium channels in rat primary sensory cortex pyramidal neurons
Authors: Yin Jianyin , Fu Bao , Zhang Yu , Yu Tian
Published: April 2020

Ketamine is an intravenous anesthetic commonly used in clinical, which has sedative and analgesic effects. Potassium channels exert many physiological functions in excitable cells. Therefore, potassium channels may be one of the targets of ketamine. In this study, we used patch clamp to study the effects of ketamine on voltage-gated potassium channels in primary sensory cortex (S1) neurons. We recorded the outward potassium currents (IA) and delayed rectifier potassium currents (IK) separately. We found that ketamine both concentration-dependently inhibited IA currents and IK currents in S1 neurons. Ketamine (100 and 300 μM) induced a concentration-dependent hyperpolarizing shift in V
1/2, without affecting the slope factor (κ) or inactivation of IA. Ketamine induced a concentration-dependent hyperpolarizing shift in V
1/2 of IK, without affecting its κ. Ketamine (100 and 300 μM) did not alter the steady-state activation or its κ. Hence, ketamine inhibits IA and IK in a concentration-dependent manner in S1 pyramidal neurons. The inactivation of IA does not appear to be involved in the inhibitory effect of ketamine on IA. Ketamine inhibits IK mainly by speeding up the inactivation of IK in S1 pyramidal neurons.
Estimating the Final Epidemic Size for COVID-19 Outbreak using Improved Epidemiological Models
Authors: Ranjan Rajesh
Published: April 2020

Abstract

Final epidemic sizes of different geographical regions due to COVID-19 are estimated using logistic, SIR and generalized SEIR models. These models use different parameters which are estimated using non-linear fits from the available data. It is found that both SIR and generalized SEIR models give similar estimations for regions where curves show signs of flattening. A study of these models with data from China indicates that in such cases these estimates may be more reliable. However, recent trend indicate that unlike China, the decline in infection rate for the US and other European countries is very slow, and does not follow a symmetric normal distribution. Hence a correction is introduced to account for this very slow decline based on the data from Italy. The estimates with all these models are presented for the most affected countries due to COVID-19. According to these models, the final epidemic size in the US, Italy, Spain, and Germany could be 1.1, 0.22, 0.24 and 0.19 million respectively. Also, it is expected that curves for most of the geographical regions will flatten by the middle of May 2020.
Proteomics of protein trafficking byin vivotissue-specific labeling
Authors: Droujinine Ilia A. , Wang Dan , Hu Yanhui , Udeshi Namrata D. , Mu Luye , Svinkina Tanya , Zeng Rebecca , Branon Tess , Tabatabai Areya , Bosch Justin A. , Asara John M. , Ting Alice Y. , Carr Steven A. , Perrimon Norbert
Published: April 2020

Secreted interorgan communication factors encode key regulators of homeostasis. However, long-standing questions surround their origins/destinations, mechanisms of interactions, and the number of proteins involved. Progress has been hindered by the lack of methodologies for these factors’ large-scale identification and characterization, as conventional approaches cannot identify low-abundance factors and the origins and destinations of secreted proteins. We established anin vivoplatform to investigate secreted protein trafficking between organs proteome-wide, whereby engineered promiscuous biotin ligase BirA*G3 (a relative of TurboID) biotinylates all proteins in a subcellular compartment of one tissue, and biotinylated proteins are affinity-enriched and identified from distal organs using quantitative mass spectrometry. Using this platform, we identified 51 putative muscle-secreted proteins from heads and 269 fat body-secreted proteins from legs/muscles, of which 60-70% have human orthologs. We demonstrate, in particular, that conserved fat body-derived novel interorgan communication factors CG31326, CG2145, and CG4332 promote muscle activity. Our results indicate that the communication network of secreted proteins is vast, and we identified systemic functions for a number of these factors. This approach is widely applicable to studies in interorgan, local and intracellular protein trafficking networks, non-conventional secretion, and to mammalian systems, under healthy or diseased states.

One Sentence Summary

We developed anin vivoplatform to investigate protein trafficking between organs proteome-wide, provide a resource for interorgan communication factors, and determined conserved adipokines that affect muscles.