bluuebunny/crossref_metadata_2025 huggingface dataset:
The Influence of Concordant Complex Posture and Loading Rate on Motion Segment Failure
Authors: Schollum Meredith L. , Wade Kelly R. , Shan Zhi , Robertson Peter A. , Thambyah Ashvin , Broom Neil D.
Published: March 2018

Study Design.

Microstructural investigation of compression-induced herniation of a lumbar disc held in a concordant complex posture.

Objective.

To explore the significance of loading rate in a highly asymmetric concordant posture, comparing the mechanisms of failure to an earlier study using a nonconcordant complex posture.

Summary of Background Data.

A recent study with a nonconcordant complex posture (turning in the opposite direction to that which the load is applied) demonstrated the vulnerability of the disc to loading that is borne by one set of oblique-counter oblique fiber sets in the alternating lamellae of the annulus, and aggravated by an elevated loading rate. Given the strain rate–dependent properties of the disc it might be expected that the outcome differs if the posture is reversed.

Methods.

Forty-one motion segments from ovine 16 spines were split into two cohorts; adopting the previously employed low rate (40 mm/min) and surprise rate (400 mm/min) of loading. Both groups of damaged discs were then analyzed microstructurally.

Results.

With the lower rate loading the concordant posture significantly reduced the load required to cause disc failure than earlier described for nonconcordant posture (6.9 vs. 8.4 kN), with more direct tears and alternate lamella damage extending to the anterior disc. Contrary to this result, with a surprise rate, the load at failure was significantly increased with the concordant posture (8.08 vs. 6.96 kN), although remaining significantly less than that from a simple flexed posture (9.6 kN). Analysis of the damage modes and postures suggest facet engagement plays a significant role.

Conclusion.

This study confirms that adding shear to the posture lowers the load at failure, and causes alternate lamella rupture. Load at failure in a complex posture is not determined by loading rate alone. Rather, the strain rate–dependent properties of the disc influence which elements of the system are brought into play.

Level of Evidence: N/A
Intra-Abdominal Hypertension Is More Common Than Previously Thought: A Prospective Study in a Mixed Medical-Surgical ICU
Authors: Murphy Patrick B. , Parry Neil G. , Sela Nathalie , Leslie Ken , Vogt Kelly , Ball Ian
Published: March 2018

Objectives:

To determine the prevalence of intra-abdominal hypertension in mixed medical-surgical critically ill patients using modern definitions and measurement techniques. Secondarily to determine variables associated with intra-abdominal hypertension and ICU mortality.

Design:

A prospective observational study.

Setting:

Single institution trauma, medical and surgical ICU in Canada.

Patients:

Consecutive adult patients admitted to the ICU (n = 285).

Intervention:

Intra-abdominal pressure measurements twice a day during admission to the ICU.

Measurements and Main Results:

In 285 patients who met inclusion criteria, 30% were diagnosed with intra-abdominal hypertension at admission and a further 15% developed intra-abdominal hypertension during admission. The prevalence of abdominal compartment syndrome was 3%. Obesity, sepsis, mechanical ventilation, and 24-hour fluid balance (> 3 L) were all independent predictors for intra-abdominal hypertension. Intra-abdominal hypertension occurred in 28% of nonventilated patients. Admission type (medical vs surgical vs trauma) was not a significant predictor of intra-abdominal hypertension. Overall ICU mortality was 20% and was significantly higher for patients with intra-abdominal hypertension (30%) compared with patients without intra-abdominal hypertension (11%). Intra-abdominal hypertension of any grade was an independent predictor of mortality (odds ratio, 3.33; 95% CI, 1.46–7.57).

Conclusions:

Intra-abdominal hypertension is common in both surgical and nonsurgical patients in the intensive care setting and was found to be independently associated with mortality. Despite prior reports to the contrary, intra-abdominal hypertension develops in nonventilated patients and in patients who do not have intra-abdominal hypertension at admission. Intra-abdominal pressure monitoring is inexpensive, provides valuable clinical information, and there may be a role for its routine measurement in the ICU. Future work should evaluate the impact of early interventions for patients with intra-abdominal hypertension.
Elective Stoma Reversal Has a Higher Incidence of Postoperative Clostridium Difficile Infection Compared With Elective Colectomy: An Analysis Using the American College of Surgeons National Surgical Quality Improvement Program and Targeted Colectomy Databases
Authors: Skancke Matthew , Vaziri Khashayar , Umapathi Bindu , Amdur Richard , Radomski Michal , Obias Vincent
Published: March 2018

BACKGROUND:

Clostridium difficile infection is caused by the proliferation of a gram-positive anaerobic bacteria after medical or surgical intervention and can result in toxic complications, emergent surgery, and death.

OBJECTIVE:

This analysis evaluates the incidence of C difficile infection in elective restoration of intestinal continuity compared with elective colon resection.

DESIGN:

This was a retrospective database review of the 2015 American College of Surgeons National Surgical Quality Improvement Project and targeted colectomy database.

SETTINGS:

The intervention cohort was defined as the primary Current Procedural Terminology codes for ileostomy/colostomy reversal (44227, 44620, 44625, and 44626) and International Classification of Diseases codes for ileostomy/colostomy status (VV44.2, VV44.3, VV55.2, VV55.3, Z93.2, Z93.3, Z43.3, and Z43.2).

PATIENTS:

A total of 2235 patients underwent elective stoma reversal compared with 10403 patients who underwent elective colon resection.

INTERVENTION:

Multivariate regression modeling of the impact of stoma reversal on postoperative C difficile infection risk was used as the study intervention.

MAIN OUTCOME MEASURES:

The incidence of C difficile infection in the 30 days after surgery was measured.

RESULTS:

The incidence of C difficile infection in the 30-day postoperative period was significantly higher (3.04% vs 1.25%; p < 0.001) in patients undergoing stoma reversal. After controlling for differences in cohorts, regression analysis suggested that stoma reversal (OR = 2.701 (95% CI, 1.966–3.711); p < 0.001), smoking (OR = 1.520 (95% CI, 1.063–2.174); p = 0.022), steroids (OR = 1.677 (95% CI, 1.005–2.779); p = 0.048), and disseminated cancer (OR = 2.312 (95% CI, 1.437–3.719); p = 0.001) were associated with C difficile infection incidence in the 30-day postoperative period.

LIMITATIONS:

The study was limited because it was a retrospective database review with observational bias.

CONCLUSIONS:

Patients who undergo elective stoma reversal have a higher incidence of postoperative C difficile infection compared with patients who undergo an elective colectomy. Given the impact of postoperative C difficile infection, a heightened sense of suspicion should be given to symptomatic patients after stoma reversal. See at Video Abstract at http://links.lww.com/DCR/A553.
Open Surgical Incisions After Colorectal Surgery Improve Quality Metrics, But Do Patients Benefit?
Authors: Mullen Matthew G. , Hawkins Robert B. , Johnston Lily E. , Shah Puja M. , Turrentine Florence E. , Hedrick Traci L. , Friel Charles M.
Published: March 2018

BACKGROUND:

Surgical site infection is a frequent cause of morbidity after colorectal resection and is a quality measure for hospitals and surgeons. In an effort to reduce the risk of postoperative infections, many wounds are left open at the time of surgery for secondary or delayed primary wound closure.

OBJECTIVE:

The purpose of this study was to evaluate the impact of delayed wound closure on the rate of surgical infections and resource use.

DESIGN:

This retrospective propensity-matched study compared colorectal surgery patients with wounds left open with a cohort of patients with primary skin closure.

SETTINGS:

The American College of Surgeons National Quality Improvement Program Participant Use file for 2014 was queried.

PATIENTS:

A total of 50,212 patients who underwent elective or emergent colectomy, proctectomy, and stoma creation were included.

MAIN OUTCOME MEASURES:

Rates of postoperative infections and discharge to medical facilities were measured.

RESULTS:

Surgical wounds were left open in 2.9% of colorectal cases (n = 1466). Patients with skin left open were broadly higher risk, as evidenced by a significantly higher median estimated probability of 30-day mortality (3.40% vs 0.45%; p < 0.0001). After propensity matching (n = 1382 per group), there were no significant differences between baseline characteristics. Within the matched cohort, there were no differences in the rates of 30-day mortality, deep or organ space infection, or sepsis (all p > 0.05). Resource use was higher for patients with incisions left open, including longer length of stay (11 vs 10 d; p = 0.006) and higher rates of discharge to a facility (34% vs 27%; p < 0.001).

LIMITATIONS:

This study was limited by its retrospective design and a large data set with a bias toward academic institutions.

CONCLUSIONS:

In a well-matched colorectal cohort, secondary or delayed wound closure eliminates superficial surgical infections, but there was no decrease in deep or organ space infections. In addition, attention should be given to the possibility for increased resource use associated with open surgical incisions. See Video Abstract at http://links.lww.com/DCR/A560.
Determination of Tacrolimus Concentration and Protein Expression of P-Glycoprotein in Single Human Renal Core Biopsies
Authors: Krogstad Veronica , Vethe Nils T. , Robertsen Ida , Hasvold Grete , Ose Anne-Marthe D. , Hermann Monica , Andersen Anders M. , Chan Joe , Skauby Morten , Svensson My H. S. , Åsberg Anders , Christensen Hege
Published: March 2018

Background:

Tacrolimus (TAC) is currently the cornerstone of immunosuppressive protocols for renal transplant recipients. Despite therapeutic whole blood monitoring, TAC is associated with nephrotoxicity, and it has been hypothesized that intrarenal accumulation of TAC and/or its metabolites are involved. As TAC is a substrate of P-glycoprotein (P-gp), the expression and activity of this efflux transporter could influence the levels of TAC in renal tissue. The primary aim of this study was to develop and validate a method for quantification of TAC in tissue homogenates from single human renal core biopsies. The secondary aim was to provide measures of P-gp expression and of the demethylated metabolites of TAC in the same renal biopsy.

Methods:

Human renal tissue, with and without clinical TAC exposure, was used for method development and validation. Homogenates were prepared with bead-beating, and concentrations of TAC and its demethylated metabolites were analyzed with liquid chromatography tandem mass spectrometry after protein precipitation. A Western blot method was used for semiquantification of P-gp expression in the homogenates. The final methods were applied to renal core biopsies from 2 transplant patients.

Results:

The TAC assay showed within- and between-run mean accuracy between 99.7% and 107% and coefficients of variation ≤6.7%. Matrix effects were nonsignificant, and samples were stable for 3 months preanalytically when stored at −80°C. TAC concentrations in the renal core biopsies were 62.6 and 43.7 pg/mg tissue. The methods for measurement of desmethyl-TAC and P-gp expression were suitable for semiquantification in homogenates from renal core biopsies.

Conclusions:

These methods may be valuable for the elucidation of the pharmacokinetic mechanisms behind TAC-induced nephrotoxicity in renal transplant recipients.
Saving Lives and Preventing Injuries From Unjustified Protective Actions—Method for Developing a Comprehensive Public Protective Action Strategy for a Severe NPP Emergency
Authors: Callen J. , McKenna T.
Published: March 2018

During the response to the Fukushima Daiichi nuclear power plant (FDNPP) emergency, about 50 patients died during or shortly after an evacuation when they were not provided with the needed medical support. In addition, it has been shown that during the FDNPP emergency there were increases in mortality rates among the elderly due to long-term dislocation as a result of evacuation and relocation orders and an inability to stay in areas where residents were advised to shelter for extended periods. These deaths occurred even though the possible radiation exposure to the public was too low to result in radiation-induced deaths, injuries, or a meaningful increase in the cancer rate, even if no protective actions had been taken. These problems are not unique to the FDNPP emergency and would be expected if the recommendations of many organizations were followed. Neither the International Commission on Radiological Protection (ICRP), the U.S. Nuclear Regulatory Commission (NRC) nor the U.S Environmental Protection Agency (EPA) adequately take into consideration in their recommendations and analysis the non-radiological health impacts, such as deaths and injuries, that could result from protective actions. Furthermore, ICRP, NRC, EPA, and the U.S. Department of Homeland Security (DHS) call for taking protective actions at doses lower than those resulting in meaningful adverse radiation-induced health effects and do not state the doses at which such effects would be seen. Consequently, it would be impossible for decision makers and the public to balance all the hazards both from radiation exposure and protective actions when deciding whether a protective action is justified. What is needed, as is presented in this paper, is a method for developing a comprehensive protective action strategy that allows the public, decision makers, and others who must work together to balance the radiological with the non-radiological health hazards posed by protective actions, and to counter the exaggerated fear of radiation exposure that could lead to taking unjustified protective actions and adverse psychological, sociological, and other effects.
Reassessment of Resuspension Factor Following Radionuclide Dispersal: Toward a General-purpose Rate Constant
Authors: Marshall Shaun , Potter Charles , Medich David
Published: March 2018

A recent analysis of historical radionuclide resuspension datasets confirmed the general applicability of the Anspaugh and modified Anspaugh models of resuspension factors following both controlled and disastrous releases. While observations appear to have larger variance earlier in time, previous studies equally weighted the data for statistical fit calculations; this could induce a positive skewing of resuspension coefficients in the early time-period. A refitting is performed using a relative instrumental weighting of the observations. Measurements within a 3‐d window are grouped into singular sample sets to construct standard deviations. The resulting best-fit equations produce tamer exponentials, which give decreased integrated resuspension factor values relative to those reported by Anspaugh. As expected, the fits attenuate greater error among the data at earlier time. The reevaluation provides a sharper contrast between the empirical models and reaffirms their deficiencies in the short-lived timeframe wherein the dynamics of particulate dispersion dominate the resuspension process.
Development and Validation of the Realistic Anthropomorphic Flexible (RAF) Phantom
Authors: Lombardo Pasquale A. , Vanhavere Filip , Lebacq Anne L. , Struelens Lara , Bogaerts Ria
Published: March 2018

Voxel phantoms developed by segmenting computed tomography images are known to be more anatomically accurate than mathematical phantoms. However, due to their lack of flexibility and the complexity of voxel datasets, the use of voxel phantoms in dosimetry is often impractical. This paper describes the development of the realistic anthropomorphic flexible (RAF) polygonal mesh phantom, a novel phantom based on Boundary Representation (B-Rep) that merges anatomical accuracy and flexibility. Rather than using segmentation of tomography images, the modeling of the phantom’s organs was based on freely and commercially available anatomical atlases, ICRP 89, and recent medical literature. To validate the phantom, a high-resolution voxel version was created for the MCNPx transport code. The voxelized RAF phantom was validated by comparing it with the ICRP 110 male phantom for external irradiations with parallel beams of photons and electrons. Dose coefficients obtained from simulations with the RAF phantom were compared with those from ICRP Publication 116. Relevant differences in organ doses were found.
Joint American Nuclear Society and Health Physics Society Conference: Applicability of Radiation Response Models to Low Dose Protection Standards
Authors: Glines Wayne M. , Markham Anna
Published: March 2018

Seventy-five years after the Hanford Site was initially created as the primary plutonium production site for atomic weapons development under the Manhattan Project, the American Nuclear Society and the Health Physics Society are sponsoring a conference from 30 September through 3 October 2018, in Pasco, Washington, titled “Applicability of Radiation Response Models to Low Dose Protection Standards.” The goal of this conference is to use current scientific data to update the approach to regulating low-level radiation doses; i.e., to answer a quintessential question of radiation protection—how to best develop radiation protection standards that protect human populations against detrimental effects while allowing the beneficial uses of radiation and radioactive materials. Previous conferences (e.g., “Wingspread Conference,” “Arlie Conference”) have attempted to address this question; but now, almost 20 y later, the key issues, goals, conclusions, and recommendations of those two conferences remain and are as relevant as they were then. Despite the best efforts of the conference participants and increased knowledge and understanding of the science underlying radiation effects in human populations, the bases of current radiation protection standards have evolved little. This 2018 conference seeks to provide a basis and path forward for evolving radiation protection standards to be more reflective of current knowledge and understanding of low dose response models.
The use of National Weather Service Data to Compute the Dose to the MEOI
Authors: Vickers Linda
Published: March 2018

The Turner method is the “benchmark method” for computing the stability class that is used to compute the X/Q (s m−3). The Turner method should be used to ascertain the validity of X/Q results determined by other methods. This paper used site-specific meteorological data obtained from the National Weather Service. The Turner method described herein is simple, quick, accurate, and transparent because all of the data, calculations, and results are visible for verification and validation with published literature.
A Phase 3 Study of Micafungin Versus Amphotericin B Deoxycholate in Infants With Invasive Candidiasis
Authors: Benjamin Daniel K. , Kaufman David A. , Hope William W. , Smith P. Brian , Arrieta Antonio , Manzoni Paolo , Kovanda Laura L. , Lademacher Christopher , Isaacson Brigit , Jednachowski Deborah , Wu Chunzhang , Kaibara Atsunori , Walsh Thomas J.
Published: March 2018

Background:

Amphotericin B deoxycholate (AmB-D) is standard of care treatment for neonatal invasive candidiasis (IC). Micafungin (MCA) has broad-spectrum fungicidal activity against Candida spp. We compared the efficacy and safety of intravenous MCA with intravenous AmB-D and assessed the pharmacokinetics of MCA in infants >2–120 days of age with proven IC in a phase 3, randomized, double-blind, multicenter, parallel-group, noninferiority study (NCT00815516).

Methods:

Infants were randomized 2:1 to MCA (10 mg/kg/d) or AmB-D (1 mg/kg/d) for ≥21 days. Primary efficacy endpoint was fungal-free survival (FFS) 1 week after last study drug dose. MCA population pharmacokinetics included simulated area under the curve (AUC) at steady state and maximum plasma concentration after 2-hour infusion. AUC pharmacodynamic target exposure was 170 µg·h/mL.

Results:

Thirty infants received MCA (n = 20) or AmB-D (n = 10). The trial was terminated early because of slow recruitment. FFS was observed in 12 of 20 [60%; 95% confidence interval (CI): 36%–81%] MCA-group infants and in 7 of 10 (70%; 95% CI: 35%–93%) AmB-D-group infants. The most common treatment-emergent adverse events were anemia [MCA: n = 9 (45%); AmB-D: n = 3 (30%)] and thrombocytopenia [n = 2 (10%) and n = 3 (30%), respectively]. Model-derived mean AUC at steady state for MCA was 399.3 ± 163.9 µg·h/mL (95% prediction interval: 190.3–742.3 µg/mL); steady state and maximum plasma concentration after 2-hour infusion was 31.1 ± 10.5 µg/mL (95% prediction interval: 17.0–49.7 µg/mL). MCA exposures were above the AUC pharmacodynamic target exposure.

Conclusions:

Within the study limitations, infants with IC treated with MCA achieved similar FFS compared with AmB-D. Both agents were safe and well tolerated.
Antifungal Treatment and Outcome in Very Low Birth Weight Infants
Authors: Fortmann Ingmar , Hartz Annika , Paul Pia , Pulzer Ferdinand , Müller Andreas , Böttger Ralf , Proquitté Hans , Dawczynski Kristin , Simon Arne , Rupp Jan , Herting Egbert , Göpel Wolfgang , Härtel Christoph
Published: March 2018

Background:

The diagnostic proof of fungal infection in preterm infants is difficult. Antifungal treatment (AFT) is often initiated empirically when infants with suspected infection do not improve despite broad-spectrum antibiotic therapy. It was the aim of our study to determine the rate of exposure to empirical AFT in a large cohort of very low birth weight infants (VLBWI) of the German Neonatal Network and to address associated risks and outcomes.

Methods:

The epidemiologic database consisted of n = 13,343 VLBWI born in 54 German Neonatal Network centers between 2009 and 2015. AFT was defined as number of neonates who got any dose of at least one of the following antifungal drugs: fluconazole, amphotericin B, voriconazole and caspofungin (denominator: number of infants enrolled in German Neonatal Network) for treatment (not prophylaxis) of (suspected) fungal infection. Univariate and logistic regression analyses were used to identify risk factors for exposure to AFT and associated short-term morbidities and long-term outcomes at 5-year follow-up.

Results:

In our cohort, 724 out of 13,343 (5.4%) VLBWI were exposed to empiric AFT and had a mean gestational age of 25.7 (±2.1) weeks. Forty-four out of 13,343 (0.3%) had proven bloodstream infection with Candida spp. The main risk factors for exposure to AFT were gestational age, postnatal steroid treatment, need for abdominal surgery and use of carbapenems. Notably, AFT was associated with adverse outcomes such as bronchopulmonary dysplasia [adjusted odds ratio (OR): 1.9; 95% confidence interval (CI): 1.6–2.3; P < 0.001) and retinopathy of prematurity requiring intervention (adjusted OR: 1.69; 95% CI: 1.3–2.3; P <0.001) but not mortality. In the subgroup of infants available for 5-year follow-up (n = 895), exposure to AFT was associated with a risk for cerebral palsy (adjusted OR: 2.79; 95% CI: 1.11–7.04; P = 0.04) and intelligence quotient < 85 (adjusted OR: 2.07; 95% CI: 1.01–4.28; P = 0.049).

Conclusions:

A significant proportion of VLBWI is exposed to AFT, specifically those born <26 weeks. Exposed infants were found to have a higher risk for adverse outcomes, which may reflect their significant vulnerability in general. Given the observational design of our study, it remains unclear whether potential side effects of empirical or target AFT itself contribute to adverse outcome. Future studies need to include risk-based strategies and stewardship programs to restrict the use of antifungal management in VLBWI.
Fusobacterium necrophorum as an Emerging Pathogen of Acute Mastoiditis
Authors: Gelbart Miri , Bilavsky Efraim , Chodick Gabriel , Raveh Eyal , Levy Itzhak , Ashkenazi-Hoffnung Liat
Published: March 2018

Background:

Recent reports have reported an increase in the incidence of acute mastoiditis because of Fusobacterium necrophorum. However, the crude incidence and the specific clinical and laboratory characteristics of F. necrophorum mastoiditis in children have not been described. Our aim was to describe these features to identify high-risk patients.

Methods:

The electronic medical records of all children with acute mastoiditis at a tertiary medical center between July 2011 and December 2015 were analyzed. Using a stepwise logistic regression to identify independent risk factors for F. necrophorum, we formulated a predictive model.

Results:

F. necrophorum was identified in 13% (19/149) of mastoiditis cases with an identifiable agent. Its incidence increased 7-fold from 2.8% in 2012 to 20.4% in 2015 (P = 0.02). F. necrophorum infection had unique clinical, laboratory and prognostic features. The vast majority had complications and underwent surgical intervention. The predictive model used 4 parameters to define high-risk patients for F. necrophorum infection at admission: females, winter/spring season, prior antibiotic treatment and a C-reactive protein value >20 mg/dL (area under receiver operating characteristic curve 0.929).

Conclusions:

Clinicians should be aware of the increasing incidence of F. necrophorum mastoiditis and consider anaerobic cultures and specific anaerobic coverage in high-risk patients.
Bacterial Load and Molecular Markers Associated With Early-onset Group B Streptococcus
Authors: Seedat Farah , Brown Colin Stewart , Stinton Chris , Patterson Jacoby , Geppert Julia , Freeman Karoline , Tan Bee , Johnson Samantha Ann , Fraser Hannah , Uthman Olalekan A. , Robinson Esther R. , McCarthy Noel Denis , Clarke Aileen , Taylor-Phillips Sian
Published: March 2018

Background:

The natural history of neonatal group B Streptococcus (GBS) is poorly understood. Little is known about the bacterial factors influencing the transmission of GBS from mother to neonate, or the development of invasive early-onset GBS disease (EOGBS) in colonized neonates. We reviewed whether bacterial load and molecular markers are associated with GBS vertical transmission and progression to EOGBS.

Methods:

We searched Medline, Embase, Cochrane and Web of Science from inception to October 10, 2016, for observational studies in English. We also hand-searched reference lists of relevant publications and experts cross-checked included studies. Two reviewers independently screened studies, extracted data and appraised the quality of included studies using the Quality in Prognosis Studies tool. We conducted random-effects meta-analyses where possible and narratively synthesized the evidence in text and tables.

Results:

Seventeen studies were included from 1107 records retrieved from electronic databases and publication references. Meta-analyses of 3 studies showed that neonates colonized by serotype III had a higher risk of developing EOGBS than serotype Ia (pooled risk ratio: 1.51, 95% confidence interval: 1.12–2.03) and serotype II (risk ratio: 1.95, 95% confidence interval: 1.10–3.45). Eleven studies showed that in heavily colonized mothers, 2–3 times more neonates were colonized, and in heavily colonized neonates, up to 15 times more neonates had EOGBS, compared with light colonization. Most evidence was published before 2000 and was at risk of bias.

Conclusions:

Acknowledging the difficulty of natural history studies, well-controlled studies are needed to assess the predictive value of pathogen subtype and heavy load; they may be useful for better-targeted prevention.
A case of personal fitness tracker-assisted diagnosis of scabies
Authors: Baird Daniel , Kalus Andrea , Gardner Jennifer M.
Published: March 2018

Accelerometer-based personal fitness trackers are frequently used to record physical activity and sleep quality, and the sleep monitoring capabilities may allow accelerometry to aid in the diagnosis of disorders, which impact sleep, including dermatologic issues. We report a case of scabies in which data from a patient’s accelerometer-based fitness tracker recording sleep disturbances over time aided in the diagnosis.
Hyperpolarization-activated cyclic nucleotide–gated channels contribute to spontaneous activity in L4 C-fiber nociceptors, but not Aβ-non-nociceptors, after axotomy of L5-spinal nerve in the rat in vivo
Authors: Djouhri Laiche , Smith Trevor , Ahmeda Ahmad , Alotaibi Mohammad , Weng Xiechuan
Published: March 2018

Peripheral neuropathic pain associated with partial nerve injury is believed to be driven partly by aberrant spontaneous activity (SA) in both injured and uninjured dorsal root ganglion (DRG) neurons. The underlying ionic mechanisms are not fully understood, but hyperpolarization-activated cyclic nucleotide–gated (HCN) channels which underlie the excitatory Ih current have been implicated in SA generation in axotomized A-fiber neurons after L5-spinal nerve ligation/axotomy (SNL/SNA). Here, using a modified model of SNA (mSNA) which involves, in addition to L5-SNA, loose ligation of the L4-spinal nerve with neuroinflammation-inducing chromic gut, we examined whether HCN channels also contribute to SA in the adjacent L4-neurons. Intracellular recordings from L4-DRG neurons in control rats, and L4-DRG neurons in mSNA rats were made using in vivo voltage- and current-clamp techniques. Compared with control, L4 C-nociceptors and Aβ-low-threshold mechanoreceptors (LTMs) exhibited SA 7 days after mSNA. This was accompanied, in C-nociceptors, by a significant increase in Ih amplitude, the percentage of Ih-expressing neurons, and Ih activation rate. Hyperpolarization-activated cyclic nucleotide–gated channel blockade with ZD7288 (10 mg/kg, intravenously) suppressed SA in C-nociceptors, but not Aβ-LTMs, and caused in C-nociceptors, membrane hyperpolarization and a decrease in Ih activation rate. Furthermore, intraplantar injection of ZD7288 (100 μM) was found to be as effective as gabapentin (positive control) in attenuating cold hypersensitivity in mSNA rats. These findings suggest that HCN channels contribute to nerve injury–induced SA in L4 C-nociceptors, but not Aβ-LTMs, and that ZD7288 exerts its analgesic effects by altering Ih activation properties and/or causing membrane hyperpolarization in L4 C-nociceptors.
Bivalent ligand MCC22 potently attenuates nociception in a murine model of sickle cell disease
Authors: Cataldo Giuseppe , Lunzer Mary M. , Olson Julie K. , Akgün Eyup , Belcher John D. , Vercellotti Gregory M. , Portoghese Philip S. , Simone Donald A.
Published: March 2018

Sickle cell disease (SCD) is a chronic inflammatory disorder accompanied by chronic pain. In addition to ongoing pain and hyperalgesia, vaso-occlusive crises–induced pain can be chronic or episodic. Because analgesics typically used to treat pain are not very effective in SCD, opioids, including morphine, are a primary treatment for managing pain in SCD but are associated with many serious side effects, including constipation, tolerance, addiction, and respiratory depression. Thus, there is a need for the development of novel treatments for pain in SCD. In this study, we used the Townes transgenic mouse model of SCD to investigate the antinociceptive efficacy of the bivalent ligand, MCC22, and compared its effectiveness with morphine. MCC22 consists of a mu-opioid receptor agonist and a chemokine receptor-5 (CCR5) antagonist that are linked through a 22-atom spacer. Our results show that intraperitoneal administration of MCC22 produced exceptionally potent dose-dependent antihyperalgesia as compared to morphine, dramatically decreased evoked responses of nociceptive dorsal horn neurons, and decreased expression of proinflammatory cytokines in the spinal cord. Moreover, tolerance did not develop to its analgesic effects after repeated administration. In view of the extraordinary potency of MCC22 without tolerance, MCC22 and similar compounds may vastly improve the management of pain associated with SCD.
Wind-up in lamina I spinoparabrachial neurons: a role for reverberatory circuits
Authors: Hachisuka Junichi , Omori Yu , Chiang Michael C. , Gold Michael S. , Koerber H. Richard , Ross Sarah E.
Published: March 2018

Wind-up is a frequency-dependent increase in the response of spinal cord neurons, which is believed to underlie temporal summation of nociceptive input. However, whether spinoparabrachial neurons, which likely contribute to the affective component of pain, undergo wind-up was unknown. Here, we addressed this question and investigated the underlying neural circuit. We show that one-fifth of lamina I spinoparabrachial neurons undergo wind-up, and provide evidence that wind-up in these cells is mediated in part by a network of spinal excitatory interneurons that show reverberating activity. These findings provide insight into a polysynaptic circuit of sensory augmentation that may contribute to the wind-up of pain's unpleasantness.
Factors Associated With Self-Reported Concussion History in Middle School Athletes
Authors: Terry Douglas P. , Wojtowicz Magdalena , Cook Nathan E. , Maxwell Bruce A. , Zafonte Ross , Seifert Tad , Silverberg Noah D. , Berkner Paul D. , Iverson Grant L.
Published: March 2018

Objective:

Identifying personal characteristics associated with sustaining a concussion is of great interest, yet only a few have examined this in children. The purpose of this study was to examine the association between sex, neurodevelopmental disorders, health history, and lifetime history of self-reported concussion in 12- and 13-year-old athletes.

Design:

Cross-sectional study.

Setting:

Middle schools.

Participants:

Participants were 1744 twelve- and thirteen-year-old student athletes who completed preseason Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) testing, including a self-report questionnaire about previous concussions, developmental diagnoses, and previous medical treatment.

Independent Variables:

Age, sex, attention-deficit/hyperactivity disorder (ADHD), learning disabilities (LDs), and previous treatment for migraine.

Main Outcome Measures:

Self-reported history of concussion.

Results:

A minority of athletes (13.7%) reported previous concussions (1 concussion, n = 181; 2 concussions, n = 41; and 3+ concussions, n = 17). A small proportion reported a history of ADHD (4.4%), LD (2.8%) or migraine treatment (4.0%). Higher rates of self-reported previous concussions were associated with male sex [16.9% vs 9.1%; χ2(1) = 21.47, P < 0.001] and previous migraine treatment [31.9% vs 13.0%; χ2(1) = 20.08, P < 0.001]. There were no differences in self-reported concussion history between 12- and 13-year olds (P = 0.18) and those with/without ADHD (P = 0.41) or LDs (P = 0.06). The overall logistic regression model was statistically significant [χ2(5) = 42.01, P < 0.001] but explained only 4.3% of the variance. Previous treatment for migraine [P < 0.001, Exp(B) = 3.30] and male sex [P < 0.001, Exp(B) = 2.06] were independently associated with a self-reported concussion history, whereas age, LD, and ADHD were not (P's > 0.05).

Conclusions:

Male sex and previous migraine treatment were associated with higher rates of self-reported previous concussions in both independent and multivariate models in middle school athletes, whereas age, ADHD, and LDs were not.
Orthopedic Injuries in Professional Surfers: A Retrospective Study at a Single Orthopedic Center
Authors: Hohn Eric , Robinson Sean , Merriman Jarrad , Parrish Robin , Kramer Warren
Published: March 2018

Background:

Literature regarding surfing injuries is scarce and most studies report a high number of minor injuries. Recent literature suggests that musculoskeletal injuries are more common than previously reported. In the mid 2000s, competitive surfing has seen an increase in aerial maneuvers, as they have become more highly rewarded by the judging panel, which may be contributing to a change in injury patterns. Our goal was to evaluate orthopedic injuries in professional surfers.

Hypothesis:

Orthopedic injuries in professional surfers are diverse and have evolved with skill and technology.

Study Design:

Retrospective observational study.

Level of Evidence:

Level 4 Case Series.

Methods:

Medical records of professional surfers from a single orthopedic center between 1991 and 2016 were reviewed. Injuries sustained while surfing and chronic injuries related to surfing were included. Site of injury, diagnosis, and treatment were recorded along with demographic data.

Results:

In total, 163 injuries in 86 athletes were recorded. The median injury age was 28.5 years (range 12-62 years) and 92.6% of patients were male. The most frequently injured body parts were the knee (28.2%), ankle (22.1%), and shoulder (19%). Most knee injuries were of the medial collateral ligament at 49%, with 75% of ankle injuries being sprains, and in shoulder, 48% had instability, 42% had a rotator cuff tear, and 35% had a superior anterior–posterior labral tear. Lower extremity injuries primarily affected the surfers' back leg (72.5%). In all, 34.6% of all injuries required surgical intervention and involved shoulder injuries most the time.

Conclusions:

The most common orthopedic injuries in professional surfers involve the knee, ankle, shoulder, hip, and back. Surfers' rear extremities were preferentially injured which is the extremity responsible for power and torque. Shoulder injuries increased the probability of an operative intervention. Last, overuse injuries (femoral-acetabular impingement, rotator cuffs) occurred in the older surf population compared with more acute injuries (ankle sprains/fractures, anterior cruciate ligament tears) which is also consistent with time to surgery.
p16 Immunohistochemistry Is Not Always Required For Accurate Diagnosis of Grade 2 Squamous Intraepithelial Lesions
Authors: Sun Lulu , Zhang Lingxin , Krigman Hannah R. , Hagemann Ian S.
Published: March 2018

Objectives

Preinvasive squamous neoplasms of the lower genital tract are currently classified using a two-tier system (high- or low-grade squamous intraepithelial lesion) as directed by the Lower Anogenital Squamous Terminology (LAST) guidelines but may also be subclassified as intraepithelial neoplasia grade 1 (−IN1), −IN2, or −IN3. The LAST recommended that all diagnoses of −IN2 be supported by immunohistochemistry (IHC) for p16. We examined whether p16 and Ki-67 IHC are necessary to diagnose −IN2 when the lesion has obvious high-grade histology.

Materials and Methods

p16 and Ki-67 IHC were performed prospectively and retrospectively on vulvar, vaginal, and cervical specimens with an initial diagnosis of −IN2 based on hematoxylin and eosin morphology, and a final diagnosis was made after consensus review.

Results

Five of 46 prospective and four of 38 retrospective cases were p16 negative. The diagnosis of −IN2 was maintained in eight of these nine cases because of compelling high-grade squamous intraepithelial lesion histology. Overall, p16 and Ki-67 IHC altered the −IN2 diagnosis to a lower grade in only one of 84 cases (1.2%, <0.01%–7.1%). Moreover, p16 was positive in all cases where the preanalytic impression was of −IN2/3 (13/13).

Conclusions

p16 IHC lacks utility in cases of morphologically obvious −IN2, because the stain is positive in most cases. The LAST recommendation to use p16 IHC to support all diagnoses of −IN2 will result in performing the immunostain in many circumstances where it is not medically necessary. Among cases that are p16 negative, many have compelling high-grade morphology. The LAST perspective that the stain trumps histology may allow false-negative IHC results to prevail.
The aVOR App Increases Medical Students’ Competence in Treating Benign Paroxysmal Positional Vertigo (BPPV)
Authors: Dlugaiczyk Julia , Thiemer Michael , Neubert Christian , Schorn Bianca Anna , Schick Bernhard
Published: March 2018

Hypothesis:

Implementation of the “aVOR app” into teaching courses at medical school enhances students’ satisfaction with the course and increases their competence in treating benign paroxysmal positional vertigo (BPPV).

Background:

BPPV is often underdiagnosed and left untreated. One problem in teaching the management of BPPV to health care professionals is the lack of simulation-based training tools. The aVOR app (aVOR = angular vestibulo-ocular reflex) works as a bionic labyrinth that simulates the activation of the semicircular canals by rotational acceleration and the resulting vestibular evoked eye movements.

Methods:

In this prospective, randomized, controlled study, medical students at a university hospital were randomly assigned to two kinds of small instructional groups. Students of the control group (n = 67) practiced diagnostic and therapeutic maneuvers for BPPV on each other, while the participants of the study group (n = 46) used the aVOR app as a virtual patient in addition. At the end of the term, students were asked to arrange the steps of the canalith repositioning procedure in the correct order in a written test.

Results:

Quality of the teaching media was rated significantly better in the aVOR group (two-sided Mann–Whitney test: P < 0.00001). Significantly more students of the aVOR group than the control group arranged the steps of the canalith repositioning procedure correctly in the final exam (56.3% versus 25.9%, Fisher's exact test: P = 0.006).

Conclusion:

Implementation of the aVOR app as a virtual patient into small instructional courses is well adopted by medical students and increases their competence in treating BPPV.
Mathematical Representation of Standard Kt/V Including Ultrafiltration and Residual Renal Function
Authors: Sternby Jan
Published: March 2018

A new formula for calculating standard Kt/V from clinical data has been derived mathematically. It is based on using the relation between eKt/V and the pre- and postdialysis concentrations in order to find the steady state concentrations. The resulting expression for standard Kt/V depends on the treatment schedule (number, length, and spacing of treatments), residual renal function, and eKt/V and relative ultrafiltration volume of each individual treatment. These results include the effects of ultrafiltration and residual renal function also in the case with unequal treatments that may be arbitrarily distributed over the week. The new formula is found to agree, within small fractions of a percentage, with standard Kt/V from simulations of 3 and 5 days per week schedules. Several approximations are also suggested and their accuracies analyzed. It is shown that the use of the midweek eKt/V and ultrafiltration for all treatments of the week is an acceptable approximation. In the presence of residual renal function, the timing of the treatments is an important factor, and particularly in this case, the new formula shows improved accuracy over previously published formulas.
Endoscopic ultrasound-guided gallbladder drainage for acute cholecystitis with a lumen-apposing metal stent: a systematic review of case series
Authors: Manta Raffaele , Mutignani Massimiliano , Galloro Giuseppe , Conigliaro Rita , Zullo Angelo
Published: March 2018

Management of patients with acute cholecystitis unfit for surgery is challenging. Recently, endoscopic ultrasound (EUS)-guided gallbladder drainage with a lumen-apposing metal stent (LAMS) has been introduced for these patients. We performed a systematic review and pooled-data analysis in this field. A comprehensive review of case series on gallbladder drainage with EUS-guided LAMS placement was performed. Only case series with at least five patients were considered. The rates of technical success, clinical success, and adverse events were computed. Overall, nine case series with a total of 226 patients were identified. The stent was positioned successfully in 215 cases [95.1%, 95% confidence interval (CI)=92.3−98]. Clinical success was achieved in 207 patients, corresponding to a 91.6% (95% CI=88−95.2) rate at intention-to-treat analysis and 96.3% (95% CI=93.7−99) at per-protocol analysis. A total of 24 (10.6%) adverse events occurred, including 11 (4.9%) cases during the procedure, and 13 (5.7%) observed at follow-up (median=6 months; range: 2−12 months). A surgical approach was required in only 25% of patients with a major adverse event. No case of procedure-related death was reported. EUS-guided LAMS placement for gallbladder drainage in patients with acute cholecystitis not suitable for surgery is highly successful and acceptably safe.
The relationship between urinary genistein levels and serum alanine aminotransferase levels in adults in the USA: National Health and Nutrition Examination Survey 1999–2010
Authors: Marcelo Carolyn , Warwick Melissa , Marcelo Catherine , Malik Manpreet , Qayyum Rehan
Published: March 2018

Background

Genistein, a phytoestrogen with similarities to female sex hormones, has been shown to protect against oxidative stress and fibrosis in nonalcoholic fatty liver injury in animal studies. However, few studies have examined genistein’s effects on liver function in humans.

Participants and methods

We analyzed data from the National Health and Nutrition Examination Survey from 1999 to 2010. Individuals younger than 21 years, with viral hepatitis, or with serum alanine aminotransferase (ALT) at the extremes of distribution (5% on each extreme) were excluded. Urinary genistein was normalized by urinary creatinine levels. The relationship between normalized urinary genistein (nUG) and serum ALT was examined using linear regression models with and without adjustment for potential confounders, and the differential effect of sex was examined using an interaction term.

Results

Of the 9864 participants, 52% were female, 50% were White, 24% were elderly, 36% had hypertension, 12% had diabetes, and 8.1% were heavy alcohol drinkers. Serum ALT was significantly lower in the highest quartile compared with the lowest quartile of nUG (22.3 vs. 23.5 U/l; P<0.001). In adjusted models, individuals in the highest quartile had 0.75 U/l lower ALT levels than those in the lowest quartile (P=0.02). We found a significant difference in ALT levels between the lowest and highest quartiles of nUG in males, but not in females (difference in differences=1.77 U/l, interaction P=0.04).

Conclusion

We found a statistically significant association between higher nUG and lower serum ALT in males, but not in females. The sex-specific role of genistein in mitigating liver disease merits further study.