bluuebunny/crossref_metadata_2025 huggingface dataset:
Reduction in Traumatic Spine Injuries in the Thoracic and Lumbar Spine With Percutaneous Versus Open Dorsal Stabilization
Authors: Rillig Jan , Keil Holger , Jung Matthias , Grützner Paul A. , Matschke Stefan , Kreinest Michael
Published: January 2020

Study Design:

Retrospective cohort study.

Objectives:

Doubts still remain whether a sufficient reduction of vertebral body fractures can be achieved if a percutaneous surgical approach is adopted. The aim of this retrospective cohort study was to analyze the reduction and perioperative complications using a percutaneous versus open surgical approach for dorsal stabilization.

Methods:

Patients suffering from a traumatic injury of the thoracic or lumbar spine who were treated with dorsal stabilization at our level 1 trauma center were included. From January 2007 through June 2009, only the open approach was used; from June 2009 through March 2014, only the percutaneous approach with a special reduction technique was used. Retrospectively, total reduction, perioperative and intraoperative data, and postoperative complications were analyzed.

Results:

Using the percutaneous (n=185) versus open surgical approach (n=91), the mean reduction over all spinal injuries was 7.7±6.6 versus 8.3±5.5 degrees, respectively. The mean operation time was 75.5±50.2 versus 71.5±41.9 minutes, respectively. There was no significant difference between the 2 treatment groups in terms of the total reduction (P=0.753) or operation time (P=0.814).

After the percutaneous and open surgical approach, 7 (3.8%) and 22 (24.2%) complications were documented. Complications requiring interventions were more frequent in the open treatment group.

Conclusions:

Percutaneous dorsal stabilization seems to be a good alternative to the traditional open surgical approach. The fracture’s reduction is similar, whereas severe complications are reduced and the operation time is not prolonged.

Level of Evidence:

Level III—retrospective cohort study.
Propensity Score Matching
Authors: Kane Liam T. , Fang Taolin , Galetta Matthew S. , Goyal Dhruv K.C. , Nicholson Kristen J. , Kepler Christopher K. , Vaccaro Alexander R. , Schroeder Gregory D.
Published: January 2020

Propensity score matching (PSM) is a commonly used statistical method in orthopedic surgery research that accomplishes the removal of confounding bias from observational cohorts where the benefit of randomization is not possible. An alternative to multiple regression analysis, PSM attempts to reduce the effects of confounders by matching already treated subjects with control subjects who exhibit a similar propensity for treatment based on preexisting covariates that influence treatment selection. It, therefore, establishes a new control group by discarding outlier control subjects. This new control group reduces the unwanted influences of covariates, allowing for proper measurement of the intended variable. An example from orthopedic spine literature is discussed to illustrate how PSM may be applied in practice. PSM is uniquely valuable in its utility and simplicity, but it is limited in that it requires the removal of data and works primarily on binary treatments. In addition to matching, the propensity score can be used for stratification, covariate adjustments, and inverse probability of treatment weighting, but these topics are outside the scope of this paper. Personnel in the orthopedic field would benefit from learning about the function and application of this method given its common use in the orthopedic literature.
Comparative Analysis of 2 Different Types of Titanium Mesh Cage for Single-level Anterior Cervical Corpectomy and Fusion in Terms of Postoperative Subsidence and Sagittal Alignment
Authors: Hur Jung-Woo , Ryu Kyeong-Sik , Ahn Stephen , Kim Jin-Sung , Chung Ho-Jung , Song Myung-Soo
Published: January 2020

Study Design:

This was a retrospective observatory analysis study.

Objective:

The objective of this study was to compare the differences in clinical and radiologic outcomes among patients who underwent anterior cervical corpectomy and fusion (ACCF) using titanium mesh cage (TMC) with end-caps and patients who underwent ACCF using TMC without end-cap.

Summary of Background Data:

TMC has been widely used as an effective treatment option for ACCF. However, the subsidence of TMC has been observed frequently in the early postoperative period in some cases, resulting in related clinical complications.

Materials and Methods:

Patients who underwent single-level ACCF using TMC from September 2008 to June 2014 at our institute were retrospectively reviewed. Patients treated with TMC with end-cap were classified as an end-cap group, while patients treated with TMC without end-cap classified as a control group. The round press-fit–type end-caps with 2.5-degree angulation were used at both ends of the cage for the end-cap group. Patients were followed postoperatively for a minimum of 36 months with radiologic evaluation.

Results:

The subsidence was lower in the end-cap group (4.3±3.6 vs. 4.8±3.0, P<0.01), with lower rates of severe subsidence (≥3 mm) than the control group (34.2% vs. 52.1%, P<0.01). Visual analogue scale (VAS) scores for neck pain and Neck Disability Index (NDI) was reported significantly less in the study group, which showed a positive correlation with lesser severe subsidence. Also, the characteristics of subsidence differed between the 2 groups. In the end-cap group, slippage type subsidence occurred, resulting in better sagittal alignment than that in the control group.

Conclusions:

For patients undergoing single-level ACCF, using TMC with end-cap provided better clinical results and similar fusion rate, compared with using TMC without end-cap. The end-cap decreased the severity of postoperative subsidence and related neck pain. Also, sagittal alignment was well preserved, suggesting it may contribute to cervical lordosis.
Prognostic significance of lactate dehydrogenase in cabazitaxel chemotherapy for castration-resistant prostate cancer: a multi-institutional study
Authors: Shiota Masaki , Nakamura Motonobu , Yokomizo Akira , Tomoda Toshihisa , Sakamoto Naotaka , Seki Narihito , Hasegawa Shuji , Yunoki Takakazu , Harano Masahiko , Kuroiwa Kentaro , Eto Masatoshi
Published: January 2020

This multi-institutional study aimed to identify prognostic factors for cabazitaxel treatment of castration-resistant prostate cancer (CRPC). This study included 74 Japanese patients with CRPC who were treated with cabazitaxel between 2014 and 2017. Associations between clinicopathological factors including serum markers and progression-free survival (PFS) and overall survival (OS) were investigated. On multivariate analysis, high Gleason score [≥9 vs. ≤7; hazard ratio (HR), 95% confidence interval (CI): 2.00 (1.01–4.34); P = 0.047], presence of pain [HR, 95% CI: 2.02 (1.14–3.58); P = 0.016], and lactate dehydrogenase (LDH) level [HR, 95% CI: 47.31 (3.79–577.49); P = 0.0019] were significantly associated with PFS. Similarly, number of docetaxel cycles [HR, 95% CI: 0.050 (0.0037–0.45); P = 0.0057], performance status [≥2 vs. 0; HR, 95% CI: 5.07 (1.57–16.24); P < 0.0001], and LDH level [HR, 95% CI: 2946 (50–420994); P = 0.0001] were significantly associated with OS. This study showed that LDH level is robustly prognostic for both PFS and OS in cabazitaxel chemotherapy for CRPC.
miR-21 modulates cisplatin resistance of gastric cancer cells by inhibiting autophagy via the PI3K/Akt/mTOR pathway
Authors: Gu Yifan , Fei Zhewei , Zhu Ronghua
Published: January 2020

Resistance to cisplatin (DDP) remains a major obstacle in the control of gastric cancer (GC) progression. A previous study revealed that microRNA-21 (miR-21) contributes to DDP resistance in GC cells via the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway. The aim of the current study was to explore the mechanisms underlying the cytoprotective function of miR-21. In this study, DDP-resistant GC cells were obtained by continuous exposure of human gastric adenocarcinoma cells to increasing concentrations of DDP. Western blot analysis was used to evaluate activation of the PI3K/Akt/mechanistic target of rapamycin kinase (mTOR) pathway. The level of miR-21 was altered by transfection of miR-21 mimic and inhibitor. Autophagy was assessed by detecting autophagosome formation, Beclin-1 and LC3 expression. An Annexin V-propidium iodide assay was performed to estimate the survival and death of GC cells. GC cells became refractory to the growth inhibition and apoptosis induced by DDP treatment, activation of Akt and mTOR were increased in DDP-resistant GC cells. Inhibition of autophagy decreased the sensitivity of GC cells to DDP, and autophagy induction produced the opposite effect. DDP-resistant GC cells expressed higher levels of miR-21 compared with the parent cells. Transfection of GC cells with miR-21 mimics contributed to restored DDP resistance by suppressing autophagy, while miR-21 inhibitor sensitized DDP-resistant GC cells by promoting autophagy. In conclusion, the results demonstrated that miR-21 is associated with DDP resistance in GC cells by inhibiting autophagy via the PI3K/Akt/mTOR pathway, and autophagy inducers could be therapeutic targets for the effective treatment of DDP resistance in GC.
Pressurized Intraperitoneal Aerosol Chemotherapy, a Palliative Treatment Approach for Patients With Peritoneal Carcinomatosis: Description of Method and Systematic Review of Literature
Authors: Winkler Carl S. , Sandhu Jaspreet , Pettke Erica , Merchea Amit , Fong Yuman , Kumara H.M.C. Shantha , Whelan Richard L.
Published: January 2020

BACKGROUND:

Peritoneal metastases arise in patients with a variety of primary cancers, and are associated with a poor prognosis. Systemic chemotherapy is the mainstay of treatment; however, the morbidity is considerable and the survival benefit is modest. Cytoreductive surgery and heated intraperitoneal chemotherapy is a potentially curative treatment available to a minority of patients; however, most develop recurrent disease. A novel palliative treatment for peritoneal metastases, pressurized intraperitoneal aerosol chemotherapy, has recently been introduced. Pressurized intraperitoneal aerosol chemotherapy utilizes an aerosol of chemotherapy in carbon dioxide gas. It is instilled into the abdomen under pressure via laparoscopic ports. No cytoreduction is performed. Pressurized intraperitoneal aerosol chemotherapy can be repeated at 6-week intervals. Oxaliplatin or cis-platinum and doxorubicin have been used to date.

OBJECTIVE:

This study aims to systematically review and evaluate the method, and the preclinical and early clinical results of pressurized intraperitoneal aerosol chemotherapy.

DATA SOURCES:

Medline and the Cochrane Library were the data sources for the study.

STUDY SELECTION:

Peer-reviewed series of greater than 10 patients, with sufficient patient data, through April 2019, were selected.

INTERVENTION:

Patients with peritoneal metastases underwent pressurized intraperitoneal aerosol chemotherapy.

MAIN OUTCOME MEASURES:

Patient dropout, histologic tumor response, adverse events, and 30-day mortality were the primary outcomes measured.

RESULTS:

A total of 921 patients with peritoneal metastases were brought to the operating room for pressurized intraperitoneal aerosol chemotherapy. The number of pressurized intraperitoneal aerosol chemotherapy treatments administered was as follows: 1 treatment, 862 (94%); 2 treatments, 645 (70%); and 3 treatments, 390 patients (42%). Initial laparoscopic access was not possible in 59 patients (6.4%). Common Terminology Criteria for Adverse Events grade 3 or higher were noted in 13.7% of the patients who, collectively, underwent a total of 2116 treatments. The 30-day mortality was 2.4% (22/921).

LIMITATIONS:

This study was limited by the heterogeneity of reported data and primary tumor types and by the lack of long-term survival data.

CONCLUSIONS:

Early clinical results are encouraging, but tumor-specific, prospective, randomized trials are needed to compare pressurized intraperitoneal aerosol chemotherapy to systemic chemotherapy. This method has yet to be introduced to the United States. It is another therapeutic option for patients with peritoneal metastases and will broaden the patient base for future clinical trials.
Population Pharmacokinetics of Vancomycin Under Continuous Renal Replacement Therapy Using a Polymethylmethacrylate Hemofilter
Authors: Yamazaki Shingo , Tatebe Mizuki , Fujiyoshi Masachika , Hattori Noriyuki , Suzuki Tatsuya , Takatsuka Hirokazu , Uchida Masashi , Suzuki Takaaki , Ishii Itsuko
Published: January 2020

Background:

Although continuous hemodiafiltration (CHDF) is often performed in critically ill patients during sepsis treatment, the pharmacokinetics of vancomycin (VCM) during CHDF with a polymethylmethacrylate hemofilter (PMMA-CHDF) have not been revealed. In this study, the authors aimed to describe the population pharmacokinetics of VCM in critically ill patients undergoing PMMA-CHDF and clarify its hemofilter clearance (CLhemofilter).

Methods:

This single-center, retrospective study enrolled patients who underwent intravenous VCM therapy during PMMA-CHDF at the intensive care unit of Chiba University Hospital between 2008 and 2016. A population analysis was performed, and CLhemofilter was assessed.

Results:

Twenty-five patients were enrolled. Median body weight (BW) and Sequential Organ Failure Assessment (SOFA) score were 63 kg and 15, respectively. Mean conditions for CHDF were 107.5 ± 18.3 mL/min for blood flow rate and 26.3 ± 6.3 mL/kg/h for effluent flow rate. The mean parameter estimates were distribution volume of the central compartment (V1), 59.1 L; clearance of the central compartment (CL1), 1.35 L/h; distribution volume of the peripheral compartment (V2), 56.1 L; and clearance of the peripheral compartment (CL2), 3.65 L/h. BW and SOFA score were significantly associated with V1 (P < 0.05) and CL1 (P < 0.05), respectively, and were thus selected as covariates in the final model. The estimated dosage of VCM to achieve a target area under the concentration–time curve/minimum inhibitory concentration ≥400 was 27.1 mg/kg for loading and 9.7 mg/kg every 24 hours for maintenance; these dosages were affected by BW and SOFA score. Mean CLhemofilter obtained from 8 patients was 1.35 L/h, which was similar to CL1.

Conclusions:

The authors clarified the pharmacokinetics and CLhemofilter of VCM in PMMA-CHDF patients. The PK of VCM in patients undergoing CHDF appeared to vary not only with the CHDF setting and BW but also with SOFA score.
Hot flashes are associated with altered brain function during a memory task
Authors: Maki Pauline M. , Wu Minjie , Rubin Leah H. , Fornelli Deanne , Drogos Lauren L. , Geller Stacie , Shulman Lee P. , Banuvar Suzanne , Little Deborah M. , Conant Rhoda J.
Published: January 2020

Objective:

Vasomotor symptoms (VMS) are associated with decreased memory performance and alterations in brain function. We conducted a preliminary examination of VMS and patterns of brain activity during a verbal memory task to provide insights into the VMS-related brain mechanisms that can contribute to memory problems in midlife women.

Methods:

Fourteen postmenopausal women (mean age 53.5, 64% African-American) with moderate-to-severe VMS (>35/wk) and not taking hormone therapy completed functional magnetic resonance imaging (fMRI) assessments during word encoding and recognition, 24-hour physiologic VMS monitoring, symptom questionnaires, and two verbal memory tests.

Results:

In regression analyses, a higher number of physiologic VMS, but not reported VMS, was associated with worse verbal memory on immediate and delayed logical memory (r = 0.53 and r = 0.72, P < 0.05). On fMRI assessments, a higher number of physiologic VMS, but not subjective VMS, was associated with greater activation in the left orbitofrontal cortex, left medial and superior frontal gyrus, right superior frontal gyrus, and right parahippocampal gyrus during the encoding task (P < 0.005). During the recognition task, physiologic VMS were associated with greater activation in the left medial and superior frontal gyrus, left parahippocampal gyrus and hippocampus, right medial and superior frontal gyrus, right parahippocampal gyrus and hippocampus (P < 0.005), and with decreased activation in the ventral medial prefrontal cortex (P < 0.005). Those associations were independent of symptoms and hormone levels.

Conclusions:

Preliminary data suggest that VMS may contribute to memory performance through effects on the hippocampus and prefrontal cortex. Larger studies are warranted to determine the robustness of these initial observations.

Video Summary:
http://links.lww.com/MENO/A508.
Safety of vaginal estrogens: a systematic review
Authors: Crandall Carolyn J. , Diamant Allison , Santoro Nanette
Published: January 2020

Objective:

This systematic review included clinical trials of Food and Drug Administration-approved vaginal estrogens. The primary objective of this systematic review was to examine the comparative safety of the Food and Drug Administration-approved vaginal estrogen preparations among postmenopausal women.

Methods:

We performed a PubMed search of the primary literature from January 1, 1966 to July 16, 2019 for English-language clinical trials. Manual review of retrieved citations identified additional citations.

Results:

Of 882 retrieved citations, 75 clinical trials met inclusion criteria. Maximum trial duration was 52 weeks. None of the trials predesignated breast or endometrial cancer, cardiovascular events, or venous thromboembolism as primary outcomes. Studies were not designed to rule out an increase in endometrial carcinoma risk with long-term use of vaginal estrogen. There were few head-to-head comparisons. Fifty trials examined serum sex steroid and gonadotrophin levels; assay methodologies varied. Serum estradiol levels were 11 pg/mL at baseline or during placebo use and increased to a mean of 30 pg/mL after treatment. Estradiol levels were usually highest during the first 12 weeks of treatment, and were higher for estrogen creams than for inserts or rings. The 22 trials of endometrial thickness and the 15 trials of endometrial biopsy did not clearly demonstrate endometrial proliferation after vaginal estrogen treatment, but data were limited, and studies did not always perform systematic endometrial biopsy.

Conclusions:

Newer low-dose estradiol rings, tablets, and inserts appear to induce the least increases in serum hormones, possibly indicating greater safety. Limited evidence in trials lasting up to 52 weeks suggest endometrial safety of vaginal estrogen use. Long-term trials are needed.

Video Summary:
http://links.lww.com/MENO/A513.
Endometrial safety and bleeding profile of a 17β-estradiol/progesterone oral softgel capsule (TX-001HR)∗
Authors: Mirkin Sebastian , Goldstein Steven R. , Archer David F. , Pickar James H. , Graham Shelli , Bernick Brian
Published: January 2020

Objective:

The aim of the study was to evaluate the effect of a single-capsule 17β-estradiol/progesterone (E2/P4), TX-001HR, on endometrial safety, to report on amenorrhea and bleeding patterns of users, and to identify predictors of amenorrhea.

Methods:

The REPLENISH trial (NCT01942668) evaluated use of TX-001HR in menopausal women (40-65 y) with vasomotor symptoms (VMS) and a uterus. Women were randomized to daily E2/P4 (mg/mg: 1/100, 0.5/100, 0.5/50, or 0.25/50), or placebo for 12 months. Incidence rate of endometrial hyperplasia was calculated from endometrial biopsies conducted at screening and study completion. Women reported bleeding and spotting in daily diaries. The number of bleeding and/or spotting days and the proportion of women with no bleeding or amenorrhea were compared between treatment and placebo using the Fisher exact test. Predictors of cumulative amenorrhea were assessed by univariate analyses.

Results:

Women (n = 1,835) who took at least one study dose comprised the safety population; 1,255 had baseline and 12-month biopsies and comprised the endometrial safety population. Incidence of endometrial hyperplasia was ≤0.36% with any dose of TX-001HR after 1 year of use (one-sided upper 95% confidence interval ≤4%). Cumulative amenorrhea (no bleeding/spotting) rates increased over time and were relatively high from cycle 1 to 13 with TX-001HR (56%-73%; placebo 79%; P < 0.05 except with 0.25/50 dose). Few vaginal bleeding adverse events (1.0%-4.6% TX-001HR vs 0.7% placebo) were reported and discontinuations due to bleeding were low (0.4%-1.4% vs 0%). Cumulative amenorrhea was significantly more frequent in older women, those further from their last menstrual period, and those with lower baseline E2 concentrations (all; P < 0.01).

Conclusions:

All doses of TX-001HR provided endometrial protection and were associated with an improved bleeding profile over time; older age, further last menstrual period, or lower baseline E2 may predict amenorrhea with TX-001HR.
Short rest between shifts and risk of hypertension in hospital workers
Authors: Cho Yun-Sik , Lee Seungho , Yoon Jin-Ha , Lee Jieun , Park Jae Bum , Lee Kyung-Jong , Jeong Inchul
Published: January 2020

Objectives:

Shift work is related to hypertension and other cardiovascular diseases, and short shift intervals of less than 11 h (quick returns) are reported to be related to health problems, including sleep disturbance and fatigue. However, its cardiovascular effect has rarely been examined. The purpose of this study was to investigate the relationship between quick returns, consecutive night shifts, and risk of hypertension in hospital workers.

Methods:

Data collected from a medical examination of 1372 nonhypertensive shift workers in a hospital were retrospectively followed up. Demographic factors (sex and age), lifestyle habits (smoking, alcohol use, exercise, and obesity), and work-related factors (working hours, shift work experience, consecutive night shifts, and quick returns status) were included in the analyses. Multivariate Cox proportional-hazard models were conducted to estimate hazard ratio and 95% confidence interval (CI).

Results:

The findings showed that quick returns was related to an increased risk of hypertension (hazard ratio, 95% CI: 1.88, 1.00–3.54), whereas consecutive night shifts were not. However, the risk of hypertension was significantly higher in workers with quick returns and 2–3 days of consecutive night shifts (3.33, 1.18–9.39) and those with quick returns and at least 4 days of consecutive night shifts (3.79, 1.22–11.76), compared with the reference group.

Conclusion:

The findings of this study indicate that short shift intervals and consecutive night shifts are related to an increased risk of hypertension in shift-working hospital workers.
Kidney-specific lymphangiogenesis increases sodium excretion and lowers blood pressure in mice
Authors: Balasubbramanian Dakshnapriya , Baranwal Gaurav , Clark Mary-Catherine C. , Goodlett Bethany L. , Mitchell Brett M. , Rutkowski Joseph M.
Published: January 2020

Objective:

Hypertension is associated with renal immune cell accumulation and sodium retention. Lymphatic vessels provide a route for immune cell trafficking and fluid clearance. Whether specifically increasing renal lymphatic density can treat established hypertension, and whether renal lymphatics are involved in mechanisms of blood pressure regulation remain undetermined. Here, we tested the hypothesis that augmenting renal lymphatic density can attenuate blood pressure in established hypertension.

Methods:

Transgenic mice with inducible kidney-specific overexpression of VEGF-D (’KidVD+’ mice) and KidVD− controls were administered a nitric oxide synthase inhibitor, l-NAME, for 4 weeks, with doxycycline administration beginning at the end of week 1. To identify mechanisms by which renal lymphatics alter renal Na+ handling, Na+ excretion was examined in KidVD+ mice during acute and chronic salt loading conditions.

Results:

Renal VEGF-D induction for 3 weeks enhanced lymphatic density and significantly attenuated blood pressure in KidVD+ mice whereas KidVD− mice remained hypertensive. No differences were identified in renal immune cells, however, the urinary Na+ excretion was increased significantly in KidVD+ mice. KidVD+ mice demonstrated normal basal sodium handling, but following chronic high salt loading, KidVD+ mice had a significantly lower blood pressure along with increased urinary fractional excretion of Na+. Mechanistically, KidVD+ mice demonstrated decreased renal abundance of total NCC and cleaved ENaCα Na+ transporters, increased renal tissue fluid volume, and increased plasma ANP.

Conclusion:

Our findings demonstrate that therapeutically augmenting renal lymphatics increases natriuresis and reduces blood pressure under sodium retention conditions.
Detection of Embedded Low-level Radioactive Shrapnel after the Explosion of a Radiological Dispersal Device in Radiological Emergency Imaging
Authors: Majewski Matthäus , Nestler Kai , Veit Daniel A. , Diekmeyer Birte , Waldeck Stephan , Port Matthias , Becker Benjamin V.
Published: January 2020

Concern about the threat of a terrorist attack with a Radiological Dispersal Device has increased considerably over the last few years, and this comes along with an immense challenge, especially regarding medical treatment of combined injuries with incorporated radioactive fragments. In such scenarios, the identification and surgical exploration of radioactive fragments is a major issue to prevent further radiation-induced effects like wound healing disorders, onset of acute radiation syndrome, and as a late-effect cancer. However, in a usual emergency setting, it is unclear how this task can be achieved. Within this study, we evaluated the feasibility of different radiological methods to identify and locate an incorporated radioactive fragment. We placed two different 137Cs sources and several non-radioactive fragments representing sham control samples within a human spine phantom. Standard emergency imaging procedures were performed, including plane radiography and different CT scans (64 row, 384 row dual energy, 320 row without iterative metal artifact reduction), respectively. Eight radiologists were blinded toward the results and asked to identify the radioactive fragments within the provided images. For both sources, correct identification was rather low (15.63%). Furthermore, none of the questioned radiologists (N = 0) stated that they were able to identify the radioactive shrapnel distinctly. Positive predictive value was accordingly low (15.63%). Most participants recommended a scintigraphy-based technique for identification (26.67%) rather than radiographic procedures (6.67%). Identification and location of incorporated small radioactive fragments with low energies by standard radiological procedures prior to surgical exploration is not promising. Nevertheless, procedures that can achieve this aim are needed direly in the case of a terrorist attack with a radiological dispersal device and should be available in an emergency department.
Gutted! Unraveling the Role of the Microbiome in Major Depressive Disorder
Authors: Bastiaanssen Thomaz F. S. , Cussotto Sofia , Claesson Marcus J. , Clarke Gerard , Dinan Timothy G. , Cryan John F.
Published: January 2020

Microorganisms can be found in virtually any environment. In humans, the largest collection of microorganisms is found in the gut ecosystem. The adult gut microbiome consists of more genes than its human host and typically spans more than 60 genera from across the taxonomic tree. In addition, the gut contains the largest number of neurons in the body, after the brain. In recent years, it has become clear that the gut microbiome is in communication with the brain, through the gut–brain axis. A growing body of literature shows that the gut microbiome plays a shaping role in a variety of psychiatric disorders, including major depressive disorder (MDD). In this review, the interplay between the microbiome and MDD is discussed in three facets. First, we discuss factors that affect the onset/development of MDD that also greatly impinge on the composition of the gut microbiota—especially diet and stressful life events. We then examine the interplay between the microbiota and MDD. We examine evidence suggesting that the microbiota is altered in MDD, and we discuss why the microbiota should be considered during MDD treatment. Finally, we look toward the future and examine how the microbiota might become a therapeutic target for MDD. This review is intended to introduce those familiar with the neurological and psychiatric aspects of MDD to the microbiome and its potential role in the disorder. Although research is in its very early days, with much yet to be the understood, the microbiome is offering new avenues for developing potentially novel strategies for managing MDD.
Comparison of Thickness-Function and Vessel Density-Function Relationship in the Superior and Inferior Macula, and in the Superotemporal and Inferotemporal Peripapillary Sectors
Authors: Holló Gábor
Published: January 2020

Précis:

In primary open-angle glaucoma (POAG), unlogged mean macular hemifield visual field sensitivity correlates significantly better with superficial capillary vessel density (VD) than with ganglion cell complex (GCC) thickness of the opposite macular hemifield.

Purpose:

The aim of this study was to compare the relationship of the spatially corresponding superficial retinal capillary VD and retinal thickness parameters with the corresponding visual field sensitivity, for the superior and inferior macula, and the superotemporal and inferotemporal peripapillary sectors, respectively.

Patients and Methods:

One eye of 27 POAG, 14 ocular hypertensive, and 9 healthy participants were subjected to optical coherence tomography angiography imaging with the Angiovue optical coherence tomography and Octopus G2 perimetry on the same day. Superior and inferior unlogged hemifield average macular sensitivity was correlated with the opposite macular hemifield VD and GCC thickness, respectively. Correlation of visual field cluster unlogged average sensitivity with the spatially corresponding sector VD and sector retinal nerve fiber layer thickness were compared for the superotemporal and inferotemporal peripapillary sector, respectively.

Results:

For all participants and the glaucoma population, the correlations for macular hemifield GCC were strong or very strong (r: 0.554 to 0.737, P<0.01). In these groups, the correlations for macular hemifield VD were all very strong (r: 0.823 to 0.838, P<0.0001) and significantly higher than the corresponding correlations for hemifield GCC (P≤0.050). No significant difference between the corresponding correlations was found in the combined normal and ocular hypertensive group for the macular hemifields, or in either population for the peripapillary sectors.

Conclusion:

Our results suggest that, in contrast to superotemporal and inferotemporal peripapillary sectors in which the thickness-function and VD-function relationships are similar, in POAG, for the macular hemifields, the VD-function relationship is stronger than the thickness-function relationship.
Changes in Prostaglandin-associated Periorbital Syndrome After Switch from Conventional Prostaglandin F2α Treatment to Omidenepag Isopropyl in 11 Consecutive Patients
Authors: Nakakura Shunsuke , Terao Etusko , Fujisawa Yasuko , Tabuchi Hitoshi , Kiuchi Yoshiaki
Published: January 2020

Purpose:

We evaluated the recovery of patients with PAPS for whom the treatment regimen switched from conventional prostaglandin F2α analogues to a new selective prostaglandin-EP2 agonist: omidenepag isopropyl.

Patients and Methods:

From November 2018 to July 2019, we prospectively evaluated 11 patients who had been using conventional PGF2α drugs. Digital photographs of the patients were taken before the start of omidenepag isopropyl therapy and ~3 and 6 months after. Three independent observers used the photographs to judged recovery according to the 5 signs of PAPS: deepening of the upper eyelid sulcus (DUES), flattening of the lower eyelid bags, upper eyelid ptosis, ciliary hypertrichosis, and periorbital skin hyperpigmentation.

Results:

The mean age of patients was 61, and 7 patients were female. The original PGF2α drugs were bimatoprost, latanoprost, travoprost, and tafluprost. The mean duration of PGF2α treatment was 65 months. PAPS signs were evaluated in 10 patients after 3 months and in all 11 patients after 6 months: After 3 and 6 months, DUES improved in 3 and 3 patients, respectively; flattening of the lower eyelid bags improved in 1 and 2 patients, respectively; upper eyelid ptosis did not improve in any patients; ciliary hypertrichosis improved in 0 and 2 patients, respectively; and eyelid pigmentation improved in 2 and 8 patients, respectively. The 3 patients who showed improvement in DUES at 6 months had all previously used bimatoprost.

Conclusions:

Some PAPS signs improved after patients started taking omidenepag isopropyl. Our findings will be useful for patients taking antiglaucoma eye drops.
Cutaneous Manifestations of Campylobacter jejuni Infection
Authors: Roberts Scott C. , Stone Samuel M. , Sutton Sarah H. , Flaherty John P.
Published: January 2020

A 51-year-old man with active follicular lymphoma presented with several days of erythematous skin nodules on all extremities 2 weeks after a self-limited diarrheal illness. All serum immunoglobulin levels were found to be low. Blood cultures grew Campylobacter jejuni. The patient was given 1 week of azithromycin with complete resolution of his skin nodules. The literature of skin manifestations seen in active C. jejuni infection is reviewed. The majority of cases occur in immunocompromised hosts, many with low or no serum immunoglobulin levels. Postulated mechanisms include a lack of secretory immunoglobulin A in intestinal mucosa predisposing susceptible patients to translocated enteric pathogens; however, the precise pathogenesis underlying cutaneous manifestations is unknown.
Strength Testing of Definitive Transtibial Prosthetic Sockets Made Using 3D-Printing Technology
Authors: Nickel Eric A. , Barrons Kyle J. , Owen Meredith K. , Hand Barry D. , Hansen Andrew H. , DesJardins John D.
Published: January 2020

Introduction

Unlike endoskeletal connectors and prosthetic feet, prosthetic sockets are not subjected to structural strength testing using internationally recognized test standards, such as International Organization for Standardization (ISO) 10328. Definitive prosthetic sockets fabricated in the traditional manner have been shown to be inconsistent in the ability to withstand the loads applied by these standards. Persistent concerns regarding the strength and durability of 3D-printed prosthetic sockets are a barrier to clinical adoption of 3D-printing technologies in prosthetic socket fabrication. To develop a robust prosthetic socket design based on 3D-printing technology, an iterative development process was used with integral validation testing using the ISO 10328 loading conditions performed independently by two testing centers.

Materials and Methods

Twenty-four 3D-printed transtibial prosthetic sockets were tested using ISO 10328 loading conditions designed to represent the greatest atypical elevated loads a 125-kg user would be expected to place on their prosthesis without failure (ultimate strength test at the P6 load level). Several design iterations and variations were tested. One socket of a design that withstood the ultimate strength loading was reprinted and subjected to cyclic testing, up to 3 million cycles. All tests were conducted under the forefoot loading condition (Condition II of the ISO 10328 standard), which generates greater moments at the distal end of the socket than the heel loading condition.

Results

Early socket designs were unable to withstand the ISO 10328 ultimate strength test to the P6 load level. Successive design improvements increased the strength until a robust final design was achieved. Variations of that final design for different suspension types and a different limb model demonstrated consistent performance. The final design was significantly stronger than the initial design (P = 1.35 × 10−7). The socket that was tested for durability completed the 3 million loading cycles at the P6 load level without damage and withstood the subsequent static proof loads.

Conclusions

An iterative design process with integral structural testing can result in strong, durable prosthetic sockets made using 3D-printing technology that may be robust to variations in limb size/shape and suspension type.
Liquid biopsy for cancer screening, diagnosis, and treatment
Authors: Smania Mary A.
Published: January 2020

The goal of precision medicine in an oncology context is to offer individuals and their families the most effective and efficient methods available to screen, diagnose, and plan treatment. Much like the rapidly expanding use of circulating free DNA testing to screen for chromosomal anomalies during pregnancy, circulating tumor DNA (ctDNA) can assess for degraded DNA fragments released into the blood by tumors. Also known as liquid biopsy (LB), this technology has the potential to improve cancer screening and postdiagnosis monitoring, but it can also provide genetic information about evolving tumor characteristics, allowing clinicians to pinpoint the most appropriate treatment options and monitor response in real time. Novel uses for ctDNA are emerging almost daily, and every provider should know at least that earlier diagnosis and more targeted therapy may now be possible for many different cancers because of LB. Patients expect their providers, including nurse practitioners, to have an understanding of genomics and when advances in genomics might directly benefit them. Liquid biopsy techniques have been rapidly adopted by the oncology community, with findings moving quickly into clinical care.
The effect of mycophenolate mofetil on platelet function
Authors: Knudsen Gustav H. , Nielsen Christian , Nielsen Camilla B. , Frederiksen Henrik , Vinholt Pernille J.
Published: January 2020

Mycophenolate mofetil (MMF) raises platelet counts in patients with primary immune thrombocytopenia. However, studies indicate that MMF inhibits collagen-induced platelet aggregation, potentially increasing bleeding risk following MMF therapy. The study evaluates the in-vitro effect of MMF on platelet function. Blood samples (n = 6) from healthy donors were incubated with vehicle, MMF or mycophenolic acid (MPA) at clinically relevant concentrations. Platelet aggregation was measured with flow cytometry and 96-well light transmission aggregometry (LTA). Using flow cytometry, we measured the expression of platelet CD49b, CD42b, CD42a, CD61 and CD41. Platelet activation was measured as the expression of P-selectin and the active form of the GPIIb/IIIa receptor following agonist stimulation. Agonists were: ADP, thrombin receptor-activating peptide, collagen, collagen-related peptide and U46619. The Platelet Function Analyzer-200 was used to measure global platelet function. MMF and MPA did not change platelet aggregation regardless of the agonist used. An exception was a significant, but minor decrease in collagen-induced platelet aggregation in samples with MMF (6 ± 3%, P = 0.02) and MPA (8 ± 4%, P = 0.01) compared with vehicle (22 ± 11%). However, this was not observed using the lesser sensitive LTA method. Compared with vehicle, MPA led to a significantly lower relative disposition of the surface collagen-receptor GPVI (7.8 ± 1.8 versus 8.8 ± 2.1 mean fluorescence intensity, P < 0.001). In all other platelet-related tests, neither MMF nor MPA showed any effect. In conclusion, MMF and MPA only had a minor effect on collagen-induced platelet aggregation, with MPA reducing the relative disposition of surface GPVI receptors.
Diurnal rhythm of blood pressure in patients with polycythemia vera
Authors: Akdi Ahmet , Özeke Özcan , Karanfil Mustafa , Ertem Ahmet Göktuğ , Yayla Çağri , Demirtaş Koray , Güney Tekin , Ünal Sefa , Selçuk Mehmet Timur
Published: January 2020

Aims

Polycythemia vera increases the risk of hypertension, but there is limited information about the effect on daily blood pressure fluctuations. This study aimed to demonstrate how diurnal blood pressure rhythm is affected in polycythemia vera patients.

Methods

Fifty (50) patients (33 men; mean age 48 ± 15 years) with a diagnosis of polycythemia vera and 51 age and sex-matched healthy subjects for the control group were prospectively evaluated. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were evaluated by ambulatory blood pressure monitoring (ABPM) as average 24-hour, daytime and nighttime measures.

Results

Average 24-hour SBP and DBP, daytime SBP and DBP were similar in both groups. However, nighttime SBP and DBP were significantly higher in the polycythemia vera group compared with the control group (125.3 ± 17.2 and 73.7 ± 12.2 vs. 118.9 ± 12.2 and 69.5 ± 8.5; P = 0.034 and P = 0.044). Both nocturnal SBP fall and nocturnal DBP fall were blunted in the polycythemia vera group compared with the control group (−6.9 ± 8.9 and −11.3 ± 12.2 vs. −11.6 ± 7.7 and −16.3 ± 12.0, respectively). Both hemoglobin and hematocrit levels were positively correlated with nocturnal SBP fall (r = 0.306, P = 0.002 and r = 0.355, P < 0.001; respectively) in all patients.

Conclusion

We found that the polycythemia vera group had significantly decreased nocturnal dipping compared with healthy controls. The SBP fall was also positively correlated with hemoglobin and hematocrit levels.
Serial anti-tuberculous immune responses during the follow-up of patients with tuberculous pleurisy
Authors: Zhang Bing-Yan , Yu Zhi-Min , Yang Qing-Luan , Liu Qian-Qian , Chen Hua-Xin , Wu Jing , Wang Sen , Shao Ling-Yun , Weng Xin-Hua , Ou Qin-Fang , Gao Yan , Zhang Wen-Hong
Published: January 2020

Little is known about the decay kinetics of interferon (IFN)-γ response and its influencing factors in tuberculous pleurisy. We enrolled thirty-two patients with tuberculous pleurisy prospectively and followed up at month 0, 6, and 9, at which time peripheral venous blood was drawn for interferon gamma release assay (IGRA) by means of QuantiFERON-TB Gold In-Tube (QFT-GIT). Demographic and clinical data were captured. To identify significant predictive factors influencing the IFN-γ response, multiple linear regression analyses were performed. Percentage of CD4+, CD8+, Vγ2Vδ2 T cells and Treg cells were measured by flow cytometry. The percentage of QFT-GIT-positive patients at baseline, month 6 and month 9 were 96.9% (30/32), 90.6% (29/32) and 84.4% (27/32), respectively. Quantitative IFN-γ response at baseline were significantly correlated with symptom duration (P = .003, R2 = 0.261) and age (P = .041, R2 = 0.132). Besides, the decreases of the IFN-γ response at month 6 and month 9 were positively correlated with the IFN-γ level at baseline. The dynamic tendency of the percentages of Treg cells was similar to the IFN-γ responses at each time-point. Quantitative IFN-γ response could be influenced by host immune status, instead of disease burden and anti-tuberculosis treatment. IGRA is probably not a useful biomarker of treatment efficacy in tuberculous pleurisy.
Association of Mycoplasma fermentans and the risk of HIV-1 infection
Authors: Liu Yi , Dong Yonghai , Wen Yinghao , Peng Siping , Liao Jie , Liu Yun
Published: January 2020

Background:

Previous studies have reported the association between Mycoplasma fermentans (M. fermentans) and the risk of human immunodeficiency virus 1 (HIV-1) infection, but the results were inconsistent. The present study aims to systematically review reported studies on M. fermentans and its association with HIV-1 infection, as well as to summarize the findings using a meta-analysis.

Methods:

Studies meeting the inclusion criteria in the PubMed, Embase, China National Knowledge Infrastructure, WanFang Data, and Chongqing VIP databases up to March 2019 were identified. Cochran Q and I
2 statistics were used to assess heterogeneity. Additionally, pooled odds ratio (OR) with 95% confidence intervals (CI) were calculated and displayed by Forest plots. Also, the funnel plot, Begg test, and Egger test were used to evaluate potential publication bias. In addition, the source of heterogeneity was investigated by subgroup and sensitivity analyses.

Results:

A total of 11 studies comprising 1028 HIV-1-positive patients and 1298 controls were ultimately included in this meta-analysis. Our results indicated that M. fermentans could increase the risk of HIV-1 infection among humans (OR = 3.66, 95%CI 1.26–10.64). Subgroup analysis showed that the risk of HIV-1 infection associated with M. fermentans was, based on the geographical distribution, 1.19 (95%CI 0.33–4.33) in Europe, 2.83 (95%CI 0.94–8.52) in United States, 11.92 (95%CI 3.93–36.15) in Asia; based on the source of the sample, 2.97 (95%CI 0.89–9.95) in blood samples, 4.36 (95%CI 1.63–11.68) in urine samples; based on the detection method, 2.80 (95%CI 0.72–10.96) with the polymerase chain reaction method, 5.54 (95%CI 1.21–25.28) with other detection methods; based on the source of controls, 1.91 (95%CI 0.53–6.89) in sexually transmitted diseases individuals, and 8.25 (95%CI 2.16–31.60) in health individuals.

Conclusion:

Our study revealed evidence of the association between M. fermentans and HIV-1 infection. Considering the heterogeneity, further studies are warranted to understand the relationship between M. fermentans and HIV-1 infection.
Towards ending the human immunodeficiency virus epidemic in the US
Authors: Olatosi Bankole , Siddiqi Khairul Alam , Conserve Donaldson Fadael
Published: January 2020

Human immunodeficiency virus (HIV) testing is important for prevention and treatment. Ending the HIV epidemic is unattainable if significant proportions of people living with HIV remain undiagnosed, making HIV testing critical for prevention and treatment. The Centers for Disease Control and Prevention (CDC) recommends routine HIV testing for persons aged 13 to 64 years in all health care settings. This study builds on prior research by estimating the extent to which HIV testing occurs during physician office and emergency department (ED) post 2006 CDC recommendations.

We performed an unweighted and weighted cross-sectional analysis using pooled data from 2 nationally representative surveys namely National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey from 2009 to 2014. We assessed routine HIV testing trends and predictive factors in physician offices and ED using multi-stage statistical survey procedures in SAS 9.4.

HIV testing rates in physician offices increased by 105% (5.6–11.5 per 1000) over the study period. A steeper increase was observed in ED with a 191% (2.3–6.7 per 1000) increase. Odds ratio (OR) for HIV testing in physician offices were highest among ages 20 to 29 ([OR] 7.20, 99% confidence interval [CI: 4.37–11.85]), males (OR 1.34, [CI: 0.91–0.93]), African-Americans (OR 2.97, [CI: 2.05–4.31]), Hispanics (OR 1.80, [CI: 1.17–2.78]), and among visits occurring in the South (OR 2.06, [CI: 1.23–3.44]). In the ED, similar trends of higher testing odds persisted for African Americans (OR 3.44, 99% CI 2.50–4.73), Hispanics (OR 2.23, 99% CI 1.65–3.01), and Northeast (OR 2.24, 99% CI 1.10–4.54).

While progress has been made in screening, HIV testing rates remains sub-optimal for ED visits. Populations visiting the ED for routine care may suffer missed opportunities for HIV testing, which delays their entry into HIV medical care. To end the epidemic, new approaches for increasing targeted routine HIV testing for populations attending health care settings is recommended.