bluuebunny/crossref_metadata_2025 huggingface dataset:
Anterior Pelvic Ring: Introduction to Evaluation and Management
Authors: Marecek Geoffrey S. , Scolaro John A.
Published: August 2018

The evaluation and management of pelvic ring injuries continues to evolve. Historic treatment was primarily nonsurgical, which yielded to open surgical treatment as the benefits of restoring pelvic anatomy and stability became clear. The development of percutaneous techniques for pelvic ring fixation enabled surgeons to reduce and stabilize certain injuries without the need for large open surgical dissections. Although percutaneous iliosacral screw fixation of sacral fractures and sacroiliac disruptions is the standard for most posterior pelvic ring injuries, the evaluation and treatment of anterior pelvic ring disruptions remains a controversial topic among surgeons who treat these injuries. Universally accepted indications for anterior pelvic ring stabilization do not exist, and there is little comparative data to support one surgical technique over another. In fact, some believe that for many injuries, the anterior ring rarely requires fixation after stable fixation of the posterior pelvic ring. The purpose of this work is to present a brief history on management of the anterior pelvic ring as a component of pelvic ring disruptions and briefly review the anatomy of the anterior pelvic ring. Finally, we will introduce the current techniques available for anterior pelvic reduction/stabilization and present information on evaluation of anterior ring stability as a means of guiding treatment.
The Use of External Fixation for the Management of the Unstable Anterior Pelvic Ring
Authors: Lee Christopher , Sciadini Marcus
Published: August 2018

The objective of this article was to highlight the indications and various methods of external fixation for management of the unstable anterior pelvic ring. Although most often used temporarily in the setting of significant hemorrhage from a pelvic ring fracture, external fixation remains an option for definitive stabilization of select pelvic ring injuries. Classically, the iliac crest frame has been used, although use of the supra-acetabular frame has gained favor due to its superior bone purchase and improved biomechanics. Common complications from external fixation include pin site infections, loss of reduction, and the “external fixator deformity.”
Minimally Invasive Endoscopic-Assisted Technique for Implant Removal After Pelvic Bridge Plating
Authors: Campbell Andrew , Dugarte Anthony , Ly Thuan V.
Published: August 2018

Subcutaneous internal plate fixation for anterior pelvic ring injuries has become more common, but implants require removal, usually by 12 weeks. The purpose of this article is to report a novel, minimally invasive, endoscopic-assisted technique for the removal of subcutaneous anterior pelvic plates safely and atraumatically without violating the underlying fascia.
Immediate Weight-Bearing Protocol for the Determination of Ankle Stability in Patients With Isolated Distal Fibular Fractures
Authors: Bonness Eric K. , Siebler Justin C. , Reed Lori K. , Lyden Elizabeth R. , Mormino Matthew A.
Published: August 2018

Objective:

To evaluate an alternative protocol for allowing immediate weight-bearing (WB) as tolerated in a functional walking boot in patients with a medial clear space (MCS) of less than 4 mm on nonstressed initial radiographs with subsequent WB radiographs at 1-week follow-up to determine if this can differentiate stable from unstable distal fibular fractures.

Design:

Retrospective case series.

Setting:

Level 1 trauma center.

Patients:

Seventy-nine patients who sustained an isolated distal fibular fracture with an MCS less than 4 mm on initial non–weight-bearing radiographs during a 6-year period.

Intervention:

Patients with MCS less than 4 mm on 1-week radiographs were treated nonoperatively. Patients with MCS greater than or equal to 4 mm were treated operatively.

Main Outcome Measurements:

Medial clear space measurements on WB ankle radiographs at the time of radiographic bony union.

Results:

Two of the 79 (2.5%) patients had an MCS greater than 4 mm at 1-week follow-up with WB radiographs and underwent operative fixation. The remaining 77 patients were treated nonoperatively. All 77 patients had an MCS less than 4 mm on WB radiographs at the time of radiographic healing.

Conclusion:

These results suggest that our immediate weight-bearing protocol may be an effective method for determination of functional ankle stability only in the setting of an isolated distal fibula fracture with MCS less than 4 mm. However, it should be cautioned that careful evaluation of WB radiographs for joint asymmetry and/or MCS widening is mandatory to avoid poor outcomes.

Level of Evidence:

Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Subscapularis Peel for Open Reduction and Internal Fixation of Proximal Humerus Fractures With a Head Split
Authors: Cherney Steven M. , Murphy Ryan A. , Achor Timothy S. , Choo Andrew M.
Published: August 2018

Proximal humerus fractures involving an articular head split are rare and complex injuries. In the elderly population, arthroplasty is the optimal treatment, whereas in younger patients, the utility of arthroplasty procedures is limited by concerns of long-term implant survival. As a result, open reduction and internal fixation is still often the first-line treatment option for head-splitting injuries. The traditionally described deltopectoral or anterolateral surgical approaches to the proximal humerus rely on indirect reduction and limited visualization of the articular fragments. We present a case series of younger patients with head-split proximal humerus fractures treated with open reduction and internal fixation through a deltopectoral approach with a subscapularis peel to improve humeral head visualization, reduction, and fixation. The improved reduction may lead to better long-term outcomes and reduce the need for additional surgical procedures. In addition, there were no cases of avascular necrosis in this series.
Association of Injury Energy Level and Neurovascular Injury Following Knee Dislocation
Authors: Stewart Robert J. , Landy David C. , Khazai Ravand S. , Cohen Joseph B. , Ho Sherwin S. , Dirschl Douglas R.
Published: August 2018

Objective:

To describe the associations between mechanism of injury energy level and neurovascular injury (NVI) following knee dislocation (KD) using a large representative sample of trauma patients and to examine risk factors within these groups.

Design:

Retrospective cohort study.

Setting:

Trauma centers participating in the American College of Surgeons National Trauma Data Bank.

Participants:

Adult patients with KD without lower extremity fracture.

Intervention:

Patients were grouped as ultra-low, low, or high-energy based on injury mechanism. Univariate/multivariate analyses assessed associations of energy level with NVI and of patient characteristics with NVI within energy-level groups.

Main Outcome Measurements:

Rate of nerve and blood vessel injury.

Results:

One hundred twenty-four patients with KD were identified; 181 sustained ultra-low-energy mechanisms, 275 low-energy, and 868 high-energy. Nerve injury occurred in 6% of ultra-low-energy injuries, 7% in low-energy, and 3% in high-energy (P = 0.03). Vessel injury occurred in 21% of ultra-low-energy injuries, 17% in low-energy, and 13% in high-energy (P = 0.01). On multivariate analyses, obesity was associated with nerve injury in the ultra-low-energy group (OR 4.9; 95% CI 1.0–24.0) but not with other energy levels. Obesity was also associated with vessel injury in the ultra-low-energy group (OR 4.0; 95% CI 1.6–9.7). Smoking, hypertension, and diabetes were not associated with NVI.

Conclusions:

NVI following KD is more common after lower energy-level mechanisms. Obesity is associated with NVI in lower energy-level mechanisms. Physicians should be vigilant in screening for NVI in the setting of KD even with seemingly benign mechanisms of injury, especially in patients with obesity.

Level of Evidence:

Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Wilhelm Schulthess, Pioneer in the Treatment of Spinal Deformities
Authors: Mazzotti Antonio , Tomba Patrizia , Perna Fabrizio , Stefanini Niccolò , Viganò Anna , Faldini Cesare
Published: August 2018

Wilhelm Schulthess was a pioneer in the treatment of spinal deformities. The Rizzoli Orthopedic Institute in Bologna, Italy, awarded him in 1911 for his work: “pathology and treatment of spinal deformities”. In this paper the Swiss Clinician is remembered through the documentation still preserved at the Rizzoli institute.
Cost-effectiveness of Balloon Kyphoplasty for Patients With Acute/Subacute Osteoporotic Vertebral Fractures in the Super-Aging Japanese Society
Authors: Takahashi Shinji , Hoshino Masatoshi , Yasuda Hiroyuki , Terai Hidetomi , Hayashi Kazunori , Tsujio Tadao , Kono Hiroshi , Suzuki Akinobu , Tamai Koji , Ohyama Shoichiro , Toyoda Hiromitsu , Dohzono Sho , Kanematsu Fumiaki , Hori Yusuke , Nakamura Hiroaki
Published: August 2018

Study Design.

A propensity score matching study.

Objective.

The aim of this study was to assess the cost-effectiveness of balloon kyphoplasty (BKP) in Japan.

Summary of Background Data.

Osteoporotic vertebral fracture (OVF) is a common disease in elderly people. In Japan, the incidence of painful OVF in 2008 was estimated as 880,000, and approximately 40% of patients with painful OVF are hospitalized due to the severity of pain. Japan is the front runner among super-aged societies and rising health care costs are an economic problem.

Methods.

BKP and nonsurgical management (NSM) for acute/subacute OVF were performed in 116 and 420 cases, respectively. Quality-adjusted life years (QALY) and incremental costs were calculated on the basis of a propensity score matching study. QALY was evaluated using the SF-6D questionnaire. Finally, using a Markov model, incremental cost-effectiveness ratios (ICERs) were calculated for 71 matched cases.

Results.

In the comparison between BKP and NSM, mean patients age was 78.3 and 77.7 years, respectively (P = 0.456). The BKP procedure cost 402,988 JPY more than NSM and the gains in QALY at the 6-month follow-up were 0.153 and 0.120, respectively (difference = 0.033). ICERs for 3 and 20 years were 4,404,158 JPY and 2,416,406 JPY, respectively. According to sensitivity analysis, ICERs ranged from 652,181 JPY to 4,896,645 JPY (4418–33,168 GBP).

Conclusion.

This study demonstrated that BKP is a cost-effective treatment option for OVF in Japan. However, the effect might be blunted in patients aged > 80 years. Further research is necessary to elucidate the cost-effectiveness of BKP in this population.

Level of Evidence: 4
Toxicities with targeted therapies after immunotherapy in metastatic melanoma
Authors: Grogan Nicole , Swami Umang , Bossler Aaron D. , Zakharia Yousef , Milhem Mohammed
Published: August 2018

Over the last decade, melanoma treatment has taken rapid strides with the advent of immunotherapies and targeted agents. With these new agents, there has been a significant improvement in patient survival. However, these new treatment options may sometimes lead to unanticipated side effects that make these treatments challenging to administer and monitor. In preclinical studies, BRAF and MEK inhibitors have shown to modulate tumor microenvironment and potentiate immunotherapies. Therefore, some patients who had prior treatment with immunotherapies can develop immune toxicities even with these targeted agents due to the long half-life of these monoclonal antibodies. Herein, we present our institutional experience with regard to these unexpected toxicities with targeted agents in patients who had previous treatment with immunotherapies. This case series lays out the various side effects along with details of their management, outcomes, and patient response.
Comparative Study of the Clinical Pathology, Immunophenotype, Epstein–Barr Virus Infection Status, and Gene Rearrangements in Adult and Child Patients With Hydroa Vacciniforme–Like Lymphoproliferative Disorder
Authors: Wen Peng-Fei , Zhang Min , Wang Ting-Ting , Liu Hong-Jie , Zhang Wen-Yan , Liu Wei-Ping , Wang Lin
Published: August 2018

Background:

Hydroa vacciniforme–like lymphoproliferative disorder (HVLPD) is a rare Epstein–Barr virus (EBV)-associated lymphoma that mainly affects children.

Objectives:

To examine the similarities and differences in the clinical pathological features, EBV infection status, and gene rearrangements in adults and children patients with HVLPD.

Methods:

We compared the clinical manifestations, histopathology, immunophenotypical features, EBV infection status, and T-cell receptor gene rearrangements in the adult and children HVLPD groups.

Results:

Clinical manifestations differed between children and adults groups. The children were characterized by blisters and severe facial swelling, whereas the adults were characterized by mild facial swelling and papules. Mosquito bite was significantly related to morbidity in the children group. Histologically, the number of mast cells in the adult group was greater than in the children group (P < 0.05). There were no significant differences in EBV infection status or TCR-γ gene rearrangements between 2 groups.

Conclusions:

There were differences in clinical pathology and prognosis between the 2 groups. A higher mast cell count and T-cell phenotype might be associated with a poor prognosis.
Undifferentiated Sarcoma as Intermediate Step in the Progression of Malignant Melanoma to Rhabdomyosarcoma: Histologic, Immunohistochemical, and Molecular Studies of a New Case of Malignant Melanoma With Rhabdomyosarcomatous Differentiation
Authors: Tran Tien Anh N. , Linos Konstantinos , de Abreu Francine B. , Carlson John Andrew
Published: August 2018

Malignant melanoma (MM) may display highly variable phenotypic diversity, sometimes associated with loss of immunohistochemical melanocytic markers and acquisition of nonmelanocytic lineage of differentiation. Primary cutaneous MM with rhabdomyosarcomatous differentiation is extremely rare with only 5 reported cases in the literature. To date, a chronological progression of a MM to rhabdomyosarcoma has not been conclusively documented. A 96-year-old man underwent a re-excision of an “atypical fibroxanthoma” of the forearm, which revealed a small lentigo maligna melanoma associated with a dominant dermal high-grade spindle cell nodule admixed with a population of malignant polygonal epithelioid cells. On immunohistochemical studies, the spindle cells were completely negative for all melanocytic markers, whereas a small population of polygonal neoplastic cells at the periphery was positive for Desmin and Myo-D1, supporting early rhabdomyosarcomatous transformation. Several subsequent re-excisions demonstrated merely nodules of malignant pleomorphic epithelioid cells with rhabdomyosarcomatous differentiation and devoid of melanocytic markers. In addition, both rhabdomyosarcomatous component and original MM displayed identical mutations. Therefore, the histologic, immunohistochemical, and molecular findings documented for the first time a chronological progression from an invasive MM to a pleomorphic rhabdomyosarcoma through an intermediate stage of undifferentiated sarcoma/atypical fibroxanthoma. Interestingly, subsequent recurrences of pure rhabdomyosarcomatous component displayed skip lesions/microsatellitosis, marked tumor-infiltrative lymphocytes, and rare junctional nests of rhabdomyosarcomatous cells in the epidermis, histologic features that were not described in primary cutaneous rhabdomyosarcoma and therefore could serve as morphologic clues to the diagnosis of rhabdomyosarcomatous transformation in an MM.
A New Histologic Pattern in 6 Biopsies From Early Frontal Fibrosing Alopecia
Authors: Miteva Mariya , Sabiq Samar
Published: August 2018

Frontal fibrosing alopecia (FFA) is an irreversible scarring alopecia with unknown etiology and no cure. The goal is to establish the diagnosis in the early stage, before developing a hairless band of atrophy involving the frontal, temporal scalp and sideburns. Pathology is rarely needed once the disease is clinically apparent. The classic histologic features include follicular dropout with the absence or atrophy of the sebaceous glands and lichenoid lymphohistiocytic infiltrate with concentric layered fibrosis at the upper follicular level. We describe a common pattern that was repeatedly seen in 6 horizontally sectioned scalp biopsies from patients with early presentation of FFA suspected on trichoscopy by the focal presence of peripilar casts around terminal hairs. All biopsies revealed overall preserved follicular architecture with average number of 11 vellus follicles, atrophy of the sebaceous glands, and perifollicular lymphohistiocytic infiltrate involving the outer root sheath of the vellus follicles (n = 5). There was no perifollicular fibrosis of the vellus follicles and no lichenoid inflammation and perifollicular fibrosis of the terminal follicles. This new pattern of “inflammatory vellus involvement” most likely corresponds to an early onset of the disease. The absence of the classic features in such biopsies from early FFA can lead to misdiagnosis.
Recurrence Risk After Up-to-Date Colon Cancer Staging, Surgery, and Pathology: Analysis of the Entire Swedish Population
Authors: Osterman Erik , Glimelius Bengt
Published: August 2018

BACKGROUND:

Developments in the quality of care of patients with colon cancer have improved surgical outcome and thus the need for adjuvant chemotherapy.

OBJECTIVE:

To investigate the recurrence rate in a large population-based cohort after modern staging, surgery, and pathology have been implemented.

DESIGN:

This was a retrospective registry study.

SETTINGS:

Data from patients included in the Swedish Colorectal Cancer Registry covering 99% of all cases and undergoing surgery for colon cancer stages I to III between 2007 and 2012 were obtained.

PATIENTS:

In total, 14,325 patients who did not receive any neoadjuvant treatment, underwent radical surgery, and were alive 30 days after surgery were included.

MAIN OUTCOME MEASURES:

Tumor and node classification and National Comprehensive Cancer Network–defined risk factors for recurrence were used to assess overall and stage-specific 5-year recurrence rates.

RESULTS:

The median follow-up of nonrecurrent cases was 77 months (range, 47–118 mo). The 5-year recurrence rate was 5% in stage I, 12% in stage II, and 33% in stage III patients. In patients classified as having pT3N0 cancer with no or 1 risk factor, the 5-year recurrence rates were 9% and 11%. Risk factors for shorter time to recurrence were male sex, more advanced pT and pN classification, vascular and perineural invasion, emergency surgery, lack of central ligature, short longitudinal resection margin, postoperative complications, and, in stage III, no adjuvant chemotherapy.

LIMITATIONS:

The registry does not contain some recently identified factors of relevance for recurrence rates, and some late recurrences may be missing.

CONCLUSIONS:

The recurrence rate is less than that previously observed in historical materials, but current, commonly used risk factors are still useful in evaluating recurrence risks. Stratification by pT and pN classification and the number of risk factors enables the identification of large patient groups characterized by such a low recurrence rate that it is questionable whether adjuvant treatment is motivated. See Video Abstract at http://links.lww.com/DCR/A663.
Age- and Bodyweight-dependent Allometric Exponent Model for Scaling Clearance and Maintenance Dose of Theophylline From Neonates to Adults
Authors: Tegenge Million A. , Mahmood Iftekhar
Published: August 2018

Background:

In population pharmacokinetic modeling, bodyweight is often incorporated as an important covariate using fixed (0.75) or single-exponent model. In recent years, several variations of allometric models have been suggested for the prediction of drug clearance across a wide age range. The objective of this study is to develop and evaluate single-exponent, bodyweight-dependent allometric exponent (BDE), age-dependent exponent (ADE), and segmented regression models for predicting clearance and maintenance dose of theophylline.

Methods:

The BDE model was described by the following equation:

JOURNAL/thdm/04.03/00007691-201810000-00014/inline-formula1/v/2023-08-14T203421Z/r/image-tiff

, where L × BW−M defines the BDE for clearance. The coefficient and the exponents L and M were estimated. The ADE model consisted of several empirical exponents based on age and ranged from 0.75 (children >5 years and adults) to 1.2 (premature neonates). Data for model development and validation were based on 52 subjects each.

Results:

All structural and statistical parameters were estimated with acceptable precision for single-exponent and BDE models (<30%); however, the BDE model was superior in describing theophylline clearance across a wide age range for the training data. The segmented regression model on log-transformed data also adequately described theophylline clearance. When models were evaluated with validation data, a single-exponent model overpredicted clearance and dosing rate in premature neonates and adults with a mean prediction error of ≥50%. For premature neonates and adults, mean clearance and dosing rate were predicted within a 30% prediction error using the BDE, ADE, and segmented models.

Conclusions:

This study demonstrates that the BDE, ADE, and segmented models performed better than a single-exponent model for predicting clearance and dose of theophylline across a wide age range.
A Survey of the Prevalence and Practice Patterns of Human Acellular Nerve Allograft Use
Authors: Azouz Solomon M. , Lucas Heather D. , Mahabir Raman C. , Noland Shelley S.
Published: August 2018

Background:

There have been many technical and scientific advances over the last decade in peripheral nerve surgery. Human acellular nerve graft (HANA) has become increasingly popular but current practice patterns among hand surgeons have yet to be defined. Coding practices may not have kept up with this innovation. A 26 question survey of hand surgeons was performed to evaluate the adoption of HANA, and current coding and billing practices. The survey was sent to hand surgeons trained in orthopedic, plastic, general, and neuro surgery. The survey was designed and implemented by the Mayo Clinic Survey Center.

Results:

Four hundred sixty-one responses to the survey were received. Most respondents currently use HANA (70%). Of those surgeons who do use HANA, nearly all use it less than 10 times per month (98%). There was no significant difference in the use of HANA across different specialties. There was a significant difference in HANA use depending on practice type with higher use by those in group private practice (57%) compared with academic practice (28%), solo practice (12%), and other practice environment (3%). There was a significant difference in HANA use depending on the number of years in practice. Those in practice less than 5 years used HANA the most (32%), followed by > 20 years in practice (27%), 6–10 years in practice (16%), 16–20 years in practice (14%), and 11–15 years in practice (11%). When asked the Current Procedural Terminology code they would use to bill for the procedure of choice, the most common response was 64910 (nerve repair with synthetic conduit or vein allograft).

Conclusions:

HANA has surpassed nerve conduit as the traditional gold standard in our study with nearly 70% of hand surgeons using HANA in their practice and a greater percentage of respondents choosing HANA as their first choice to repair as compared with nerve conduit, nerve autograft, or vein graft. There remains confusion regarding appropriate billing practices for the use of HANA. Due to its common use, a Current Procedural Terminology code should specifically designated for the use of HANA in the hand.
CENTRAL RETINAL VEIN OCCLUSION IN YOUNG INDIVIDUALS
Authors: Rothman Adam L. , Thomas Akshay S. , Khan Kirin , Fekrat Sharon
Published: August 2018

Purpose:

To compare the presentation and outcomes of patients younger than 50 years versus patients aged 50 years and older with central retinal vein occlusion (CRVO).

Methods:

This single-center retrospective study included patients with CRVO presenting between January 2009 and July 2016. Charts were reviewed and data were abstracted. Presenting and final clinical parameters, treatment burden, and predisposing factors for CRVO were compared between the two groups.

Results:

Thirty-six patients younger than 50 years and 233 patients aged 50 years and older at the time of CRVO onset were included. At presentation, younger patients had better visual acuity than older patients (20/80 vs. 20/224, P = 0.001) and a lower incidence of cystoid macular edema (54 vs. 79%, P = 0.001). Twenty-one of 36 (58%) younger patients had at least one identifiable nontraditional risk factor for CRVO. At final follow-up, younger patients received fewer total intravitreal injections (3.8 ± 5.8 at 34.2 months) compared with older patients (6.5 ± 8.8, at 37.6 months, P = 0.03) and had better final acuity (20/85 vs. 20/289, P = 0.004, respectively).

Conclusion:

Younger patients had better baseline and final acuities, a lower incidence of cystoid macular edema at presentation, and received fewer intravitreal injections than older patients. Workup for etiology of CRVO in younger patients may reveal nontraditional risk factors for CRVO.
SPONTANEOUS RESOLUTION OF OPTIC DISK PIT MACULOPATHY IN A CHILD AFTER A SIX-YEAR FOLLOW-UP
Authors: Benatti Eleonora , Garoli Elena , Viola Francesco
Published: August 2018

Purpose:

Optic disk pit (ODP) is a rare congenital abnormality of the optic nerve head that can lead to a maculopathy characterized mainly by serous retinal detachment. Optic disk pit maculopathy (ODP-M) in children is rare, and at present, the best management is still unknown. Long-lasting ODP-M can lead to organic amblyopia and photoreceptor damage, whereas surgical treatments are invasive and have an uncertain prognosis. We present a case of spontaneous resolution of ODP-M in a child who was monitored morphologically and functionally during a 6-year follow-up.

Methods:

Between January 2010 and January 2016, we conducted follow-up examinations by fundus photography, optical coherence tomography, and microperimetry.

Results:

At the first visit, a 12-year-old girl was asymptomatic with a visual acuity of 20/20 in both eyes. Optic disk pit maculopathy was observed, and the progression was monitored by follow-up optical coherence tomography. A progressive anatomical improvement with a spontaneous resolution of ODP-M occurred over a 2-year period. However, at the last follow-up visit, microperimetry showed a loss of threshold values of visual sensitivity.

Conclusion:

The combination of morphologic and functional evaluation over time can be useful to determine the best management of ODP-M, particularly in children for whom the conservative approach seems to be a valid alternative to surgery.
The Glaucoma Italian Pediatric Study (GIPSy): 3-Year Results
Authors: Quaranta Luciano , Biagioli Elena , Riva Ivano , Galli Francesca , Poli Davide , Rulli Eliana , Katsanos Andreas , Longo Antonio , Uva Maurizio G. , Oddone Francesco , Torri Valter , Weinreb Robert N.
Published: August 2018

Purpose:

To investigate the efficacy and safety of a treatment strategy with latanoprost and dorzolamide in primary pediatric glaucoma patients partially responsive to surgery.

Patients and Methods:

Children with primary pediatric glaucoma with postsurgical intraocular pressure (IOP) between 22 and 26 mm Hg were eligible. At baseline, patients were administered latanoprost once daily. Depending on IOP reduction, patients were allocated to continuation of latanoprost monotherapy or addition of dorzolamide twice daily, or switch to dorzolamide monotherapy 3 times daily. Patients in the dorzolamide monotherapy group with IOP reduction <20% from baseline were considered nonresponders. The primary endpoint was the percentage of responders. Study treatment continued for 3 years or until treatment failure.

Results:

A total of 37 patients (61 eyes) were analyzed. The mean age of the patients was 4.1 years (SD: 3.8). In total, 43 eyes were included in the efficacy analysis. A total of 33 eyes (76.7%; 95% confidence interval, 61.4-88.2) were considered responders: 19 on latanoprost monotherapy, 11 on the latanoprost/dorzolamide combination, and only 3 on the dorzolamide monotherapy. The efficacy of pharmacological treatment was inversely related to central corneal thickness at the time of surgery and the age at the time of surgery. IOP reduction was 9.7 mm Hg (SD: 2.6) for latanoprost, 8.4 mm Hg (SD: 1.5) for the latanoprost/dorzolamide combination, and 9.3 mm Hg (SD: 2.5) for the dorzolamide monotherapy. None of the patients was withdrawn because of adverse events.

Conclusions:

Latanoprost alone or in combination with dorzolamide is safe and highly effective in lowering IOP in children after surgery. Nonresponders were mainly patients with early presentation of the disease.
Inner Retinal Changes in Primary Open-Angle Glaucoma Revealed Through Adaptive Optics-Optical Coherence Tomography
Authors: Wells-Gray Elaine M. , Choi Stacey S. , Slabaugh Mark , Weber Paul , Doble Nathan
Published: August 2018

Purpose:

To examine the microstructural changes in the inner nuclear layer (INL) and ganglion cell layer (GCL) in a primary open-angle glaucoma (POAG) subject at 2 timepoints, 4 months apart.

Patients and Methods:

This case-control study (1 POAG subject and 1 normal control) used the single cell, 3-dimensional volumetric imaging capability of an adaptive optics-optical coherence tomography-scanning laser ophthalmoscopy system to examine the inner retina.

Results:

At the area of greatest glaucomatous change in the POAG subject [3-degrees temporal (T), 3-degrees inferior (I), right eye], the GCL was greatly thinned at both timepoints, yet retinal ganglion cell soma remained visible amid a meshwork of capillaries. Microcystic lesions in the INL were visible at both timepoints, ranging in diameter from 8 to 43 μm on day 1 to 11 to 64 μm at 4 months, with an average diameter increase of ∼124%. Small hyperreflective features (not seen in the contralateral eye or control subject) at a depth midway through the INL seemed correlated to the development of microcysts.

Conclusions:

We demonstrate the ability to image microcystic lesions early in their development and have quantified longitudinal changes. The presence of small hyperreflective structures at a layer midway through the INL seems to be a precursor to their formation and is a potential biomarker for assessing POAG severity and progression. The adaptive optics imaging system is also able to visualize retinal ganglion cells in this subject, despite severe thinning of the GCL.
Prospective Evaluation of XEN Gel Implant in Eyes With Pseudoexfoliative Glaucoma
Authors: Mansouri Kaweh , Gillmann Kevin , Rao Harsha L. , Guidotti Jacopo , Mermoud André
Published: August 2018

Purpose:

The main purpose of this study was to compare the safety and efficacy of XEN gel implant surgery in patients with pseudoexfoliative glaucoma (PEXG) and primary open-angle glaucoma (POAG).

Setting:

This was a prospective, interventional study in a tertiary glaucoma center.

Methods:

Fifty-seven eyes (43 patients) with POAG and 53 eyes (42 patients) with PEXG with uncontrolled intraocular pressure (IOP) despite medical treatment underwent combined XEN+cataract surgery or standalone XEN surgery. Mean IOP, mean number of medications at 1-year follow-up, needling rates, and incidence of adverse effects (AEs) were analyzed. Complete success, defined as an IOP <16 mm Hg without medications at 1 year, was also analyzed.

Results:

Combined XEN+cataract surgery was performed in 72% of POAG and 75% of PEXG eyes (P=0.674), the remainder underwent standalone XEN surgery. Patient characteristics were similar between the 2 groups except for higher age for the PEXG patients (78.5±8.5 vs. 71.3± 8.7 y; P<0.001). Mean medicated IOP was 19.8±5.8 (POAG) and 19.7±8.2 (PEXG) at baseline (P=0.98) and 13.9±4.6 (−29.8%) and 13.6±4.3 mm Hg (−31%) at 1 year (P=0.87), respectively (P<0.01). Mean medications dropped from 1.9±1.6 (POAG) and 2.0±1.3 (PEXG) preoperatively to 0.4±0.8 and 0.5±0.8, respectively at 1 year (P<0.001). A total of 42% (POAG) and 63% (PEXG) eyes achieved complete success (P=0.06) at 1 year. Needling was performed in 36.8% (POAG) versus 37.7% (PEXG) (P=0.923).

Conclusions:

The XEN gel implant as a standalone or combined procedure demonstrated similar efficacy and safety results in PEXG and POAG eyes.
Multi-OMICS analyses of frailty and chronic widespread musculoskeletal pain suggest involvement of shared neurological pathways
Authors: Livshits Gregory , Malkin Ida , Bowyer Ruth C.E. , Verdi Serena , Bell Jordana T. , Menni Cristina , Williams Frances M.K. , Steves Claire J.
Published: August 2018

Chronic widespread musculoskeletal pain (CWP) and frailty are prevalent conditions in older people. We have shown previously that interindividual variation in frailty and CWP is genetically determined. We also reported an association of frailty and CWP caused by shared genetic and common environmental factors. The aim of this study was to use omic approaches to identify molecular genetic factors underlying the heritability of frailty and its genetic correlation with CWP. Frailty was quantified through the Rockwood Frailty Index (FI) as a proportion of deficits from 33 binary health deficit questions in 3626 female twins. Common widespread pain was assessed using a screening questionnaire. OMICS analysis included 305 metabolites and whole-genome (>2.5 × 106 SNPs) and epigenome (∼1 × 106 MeDIP-seq regions) assessments performed on fasting blood samples. Using family-based statistical analyses, including path analysis, we examined how FI scores were related to molecular genetic factors and to CWP, taking into account known risk factors such as fat mass and smoking. Frailty Index was significantly correlated with 51 metabolites after correction for multiple testing, with 20 metabolites having P-values between 2.1 × 10−6 and 4.0 × 10−16. Three metabolites (uridine, C-glycosyl tryptophan, and N-acetyl glycine) were statistically independent and thought to exert a direct effect on FI. Epiandrosterone sulphate, previously shown to be highly inversely associated with CWP, was found to exert an indirect influence on FI. Bioinformatics analysis of genome-wide association study and EWAS showed that FI and its covariation with CWP was through genomic regions involved in neurological pathways. Neurological pathway involvement accounts for the associated conditions of aging CWP and FI.
Admissions Variables: Predictors of Physician Assistant Student Success
Authors: Honda Trenton , Patel-Junankar Dipu , Baginski Robert , Scott Rebecca
Published: August 2018

Purpose

Physician assistant (PA) programs have heterogeneous admissions processes, but limited information is available as to which preadmission variables are associated with the greatest PA program success. We assessed the associations between preadmission criteria and PA program outcomes while accounting for numerous potential confounders and potential cohort effects.

Methods

In a sample of 147 students from a single New England PA program, we used random intercept multiple regression models to examine the associations between 2 PA program outcomes—Physician Assistant National Certifying Examination (PANCE) scores and PA program grade point averages (GPAs)—and multiple predictors of interest, including undergraduate GPA; hours of paid, hands-on patient care experience; and undergraduate institution rank. Fully adjusted models additionally controlled for age and educationally or economically disadvantaged background.

Results

In fully adjusted models, a 1-unit increase in undergraduate GPA (54.55 ± 20.32, P = .012) and a 10% increase in preadmission clinical experience hours (18.32 ± 8.50, P = .033) were significantly associated with increased PANCE scores. When PA program GPA was examined as an outcome, only undergraduate GPA was significantly associated (0.15 ± 0.05, P = .004). Undergraduate institution rank was not a significant predictor in any model.

Conclusions

Undergraduate GPA and preadmission clinical experience hours were significant predictors of student outcomes in this small, retrospective cohort study. Undergraduate institution rank was highly nonsignificant in all models. These findings add to the burgeoning literature on admissions predictors of PA program success.
Tiotropium for asthma: A summary of current guidelines and a case study
Authors: Shedd Glenn Clinton , Blenis Robert Colin
Published: August 2018

Background and purpose:

The long-acting muscarinic antagonist tiotropium received an indication for the treatment of asthma from the FDA in 2015.

Methods:

This paper summarizes much of the published findings on tiotropium and asthma and explores the heterogeneity of the asthma population vis-à-vis recent changes in guidelines for management of COPD. The accompanying case study provides an illustration of how tiotropium might be added to a patient's regimen appropriately.

Conclusions and implications for practice:

Tiotropium has been shown in many studies to be beneficial to patients with asthma as an add-on medication. It should be considered as an agent by the clinician managing patients with both allergic and non-allergic asthma.
Insecure Attachment and Hypothalamus-Pituitary-Adrenal Axis Functioning in People With Eating Disorders
Authors: Monteleone Alessio Maria , Patriciello Giuseppina , Ruzzi Valeria , Fico Giovanna , Pellegrino Francesca , Castellini Giovanni , Steardo Luca , Monteleone Palmiero , Maj Mario
Published: August 2018

Objective

Childhood attachment experiences affect adult emotion regulation and ability to cope with stressors. Therefore, insecure attachment may influence the functioning of the hypothalamic-pituitary-adrenal (HPA) axis and a dysregulation of HPA axis has been found in insecure attached healthy individuals. The effects of attachment on HPA axis activity have never been investigated in eating disorders (EDs). Therefore, we assessed the relationships between insecure attachment and the cortisol awakening response (CAR) in adults with EDs.

Methods

Seventy-eight patients with EDs (43 with anorexia nervosa, 35 with bulimia nervosa) were recruited. They completed the Experience in Close Relationships questionnaire, which provides a rating of two insecure attachment dimensions (anxiety and avoidance) and collected saliva samples to measure the CAR. Differences in the CAR between groups with high and low attachment anxiety and between groups with high and low attachment avoidance were evaluated by repeated measures two-way analysis of variance.

Results

Patients with high attachment anxiety showed a reduced CAR compared with those with low attachment anxiety (F
1,76 = 7.31, p = .008). The CAR did not differ between the groups with high and low attachment avoidance (F
1,76 = 0.01, p = .93). Patients with high levels of insecure attachment showed a more severe eating-related psychopathology.

Conclusions

Our data show, for the first time, a specific association of the anxious attachment with the HPA axis activity in EDs and suggest a possible role of attachment in the biological vulnerability to stress of adult patients with EDs.
Fully Automated 10-Minute 3D CAIPIRINHA SPACE TSE MRI of the Knee in Adults
Authors: Del Grande Filippo , Delcogliano Marco , Guglielmi Riccardo , Raithel Esther , Stern Steven E. , Papp Derek F. , Candrian Christian , Fritz Jan
Published: August 2018

Objectives

The aim of this study was to test the hypothesis that magnetic resonance imaging (MRI) of the knee with 10-minute 3-dimensional (3D) controlled aliasing in parallel imaging results in higher acceleration (CAIPIRINHA) sampling perfection with application optimized contrast using different flip angle evolutions (SPACE) turbo spin echo (TSE) protocols can replace 20-minute 2-dimensional (2D) TSE standard-of-reference protocols for the diagnosis of internal derangement.

Materials and Methods

After internal review board approval and prospective informed consent, 100 symptomatic subjects underwent MRI of the knee at 3 T and 50 symptomatic subjects at 1.5 T, consisting of 10-minute 3D CAIPIRINHA SPACE TSE and 20-minute standard-of-reference 2D TSE protocols. Two fellowship-trained musculoskeletal radiologists assessed the studies in an anonymized and randomized fashion for structural abnormalities. Descriptive statistics, interreader reliability, intermethod concordance, diagnostic definitiveness, and interchangeability tests were applied. P values equal to or smaller than 0.01 were considered significant.

Results

The interchangeability analysis showed that the 3D MRI can replace the 2D MRI protocols, whereas a superiority of 3D MRI was suggested statistically for the detection of medial and lateral meniscal tears, cartilage defects, and bone marrow edema by significantly higher common pair exact match proportions of readers (P < 0.01, respectively).The overall interreader reliabilities were 89% of exact matches for 2D TSE (κ, 0.842) and 96% of exact matches for 3D TSE (κ, 0.941) (P < 0.01). There was good intermethod concordance (κ, 0.736; range, 0.579–1.000). The interreader reliability (2D TSE: κ, 0.748 [0.603–1.000]; 3D TSE: κ, 0.901 [0.797–1.000]) and diagnostic definitiveness were significantly higher for the 3D than 2D MRI (P < 0.01).

Conclusions

10-minute 3D CAIPIRINHA SPACE TSE MRI protocols can replace 20-minute 2D TSE standard-of-reference MRI protocols for the evaluation of internal derangement of the knee by producing similar results in individual patient diagnoses, whereas interpretations of 3D CAIPIRINHA SPACE TSE MRI examinations resulted in an overall higher interreader reliability, intermethod concordance, and reader definitiveness.
Organ-specific changes in vascular reactivity and roles of inducible nitric oxide synthase and endothelin-1 in a rabbit endotoxic shock model
Authors: Zhang Zi-Sen , Chen Wei , Li Tao , Liu Liang-ming
Published: August 2018

BACKGROUND

Hemorrhagic shock-induced changes in vascular reactivity appear organ-specific. In the present study, we examined the hypothesis that vascular reactivity induced by septic shock similarly displays organ-specific differences and is regulated by inducible nitric oxide synthase (iNOS) and endothelin-1 (ET-1).

METHODS

Endotoxic shock was induced in rabbits by administration of lipopolysaccharide (LPS) (1 mg/kg), and organ specificity of vascular reactivity of superior mesenteric artery (SMA), celiac artery (CA), and left renal artery (LRA) as well as the potential involvement of iNOS and ET-1 examined.

RESULTS

Vascular reactivity of SMA, CA, and LRA was increased at the early stages and decreased at the late stages after LPS administration. Superior mesenteric artery showed the greatest decrease in vascular reactivity in response to norepinephrine (NE) (34.9%) and acetylcholine (Ach; 32.3%), followed by LRA (NE, 33.7%; Ach, 30.5%) and CA (NE, 16.2%), whereas the relaxation reactivity of CA in response to Ach was increased to 159%. The mRNA and protein levels of iNOS and ET-1 in SMA, CA, and LRA were not affected at the early stages of endotoxic shock after LPS administration but significantly increased at the late stages. Expression levels were higher in SMA than CA and LRA and negatively correlated with the decrease in vascular reactivity. The iNOS and ET-1 inhibitors, aminoguanidine (20 mg/kg) and PD-142893 (0.02 mg/kg), respectively, induced significant improvements in vascular reactivity and organ perfusion and stabilized the hemodynamic parameters in rabbits subjected to endotoxic shock.

CONCLUSION

Changes in vascular reactivity during endotoxic shock are organ-specific. Differential expression patterns of iNOS and ET-1 in different blood vessels contribute to the organ specificity of vascular reactivity.

LEVEL OF EVIDENCE

Therapeutic study, level II.
Effects of driving distance and transport time on mortality among Level I and II traumas occurring in a metropolitan area
Authors: Karrison Theodore G. , Philip Schumm L. , Kocherginsky Masha , Thisted Ronald , Dirschl Douglas R. , Rogers Selwyn
Published: August 2018

BACKGROUND

The purpose of this study was to evaluate the effects of ambulance driving distance and transport time on mortality among trauma incidents occurring in the City of Chicago, a large metropolitan area.

METHODS

We studied individuals 16 years or older who suffered a Level I or II injury and were taken to a Level I trauma center. The outcome was in-hospital mortality, including those dead on arrival but excluding those deemed dead on scene. Driving distance was calculated from the scene of injury to the trauma center where the patient was taken. Transport time was defined as the time from scene departure to arrival at the trauma center. Covariates included injury severity measures recorded at the scene. Logistic regression and instrumental variable probit regression models were used to examine the association between driving distance, transport time, and mortality, adjusting for injury severity.

RESULTS

A total of 24,834 incidents were analyzed, including 1,464 deaths. Median driving distance was 3.9 miles, and median transport time was 13 minutes. Our findings indicate that increased driving distance is associated with a modest increase in mortality, with a covariate-adjusted odds ratio of 1.12 per 2-mile increase in distance (95% confidence interval [CI], 1.05–1.20). This corresponds to an increase in overall mortality of 0.26 percentage points per 2 miles (95% CI, 0.11–0.40). Using distance as an instrumental variable, we estimate a 0.51 percentage point increase in mortality per 5-minute increase in transport time (95% CI, 0.14–0.89).

CONCLUSION

We find a modest effect of distance on mortality that is approximately linear over a range of 0 to 12 miles. Instrumental variables analysis indicated a corresponding increase in mortality with increasing transport time. Limitations of the study include the possibility of unmeasured confounders and the assumption that distance affects mortality only through its effect on transport time.

LEVEL OF EVIDENCE

Prognostic study, level III.