bluuebunny/crossref_metadata_2025 huggingface dataset:
Cyclops lesions after ACL reconstruction using either bone-tendon-bone autograft or hamstring autograft: A retrospective cohort study
Authors: Pharr Zachary K. , Mascioli Anthony A. , Dickerson Andrew B. , Throckmorton Thomas W. , Azar Frederick M.
Published: November 2019

Background:

ACL reconstruction is commonly performed with either bone-patellar tendon-bone (BPTB) autograft or hamstring autograft, each of which has inherent advantages and disadvantages; to our knowledge, no study has compared the frequency of cyclops lesions between the two autografts. By focusing on cyclops lesions, a source of knee extension loss after ACL reconstruction, we aimed to expand the comparison between these two autograft options.

Methods:

A single-center, retrospective chart review identified 1,902 patients between the ages of 8 and 66 yr who had ACL reconstruction between January 1, 2000, and October 31, 2015. Of these, 1534 received a BPTB autograft and 368 a hamstring autograft. Cyclops lesions were confirmed by a second arthroscopy in patients treated for loss of full knee extension, and the occurrences with BPTB and hamstring autograft were compared.

Results:

Cyclops lesions occurred in 14 (0.91%) of 1,534 reconstructions with BPTB autografts and five (1.35%) of 368 with hamstring autografts (P=0.39); this difference was not statistically significant. Cyclops lesions occurred in five (0.44%) of 1125 males and 14 (1.44%) of 777 females (P=0.004). This was statistically significant, illustrating a more frequent occurrence of cyclops lesions in female patients than in male patients with a relative risk of 4 (CI 1.4-11).

Conclusions:

Bone-patellar tendon-bone and hamstring autografts both are viable options for ACL reconstruction. The occurrence of cyclops lesions is a potential complication that has not been previously compared between these two graft options. We found no statistically significant difference in the frequency of cyclops lesions between the two groups, minimizing any concern for an increased risk of a cyclops lesion when choosing BPTB autograft or hamstring autograft. Surgeons should be cognizant that the relative risk of a cyclops lesion is four times higher in female patients than in male patients with either graft.

Level of Evidence:

Level III.
Planning a Proximal Femoral Varus Osteotomy in Pediatric Orthopedics
Authors: Mifsud Maximillian , Buckingham Rachel , Theologis Tim
Published: November 2019

A proximal femoral osteotomy used typically to correct increased femoral anteversion and/or a valgus/varus neck-shaft angle, is one of the most commonly performed operations in pediatric orthopedics. Surgeons with limited experience with the procedure often find conceptualization of the technique to establish the angles of correction and the decision regarding plate angle, difficult. This short article seeks to clear that confusion and describe the technique in 4 simple steps.
Berberine inhibits proliferation and migration of colorectal cancer cells by downregulation of GRP78
Authors: Gong Chenxue , Hu Xiao , Xu Yingling , Yang Jinhuan , Zong Lei , Wang Cui , Zhu Ji , Li Zhuoyu , Lu Dezhao
Published: November 2019

Human colorectal cancer (CRC), a highly malignant and metastatic carcinoma, is resistant to many present anticancer therapies. The inhibition of tumor survival and growth through receptor suppression is a promising way to treat CRC. The study aimed to investigate the effect of a natural plant triterpenoid, berberine (BBR), on SW480 cells and whether its role is mediated by Glucose-regulated protein 78 (GRP78). MTT assay, wound healing assay, and Annexin V-FITC assay were used to measure the effect of BBR on the proliferation, migration, and apoptosis of SW480 cells, respectively. Immunofluorescence and western blotting were used to evaluate both the downregulation of BBR on GRP78 and the role of GRP78 in the effect of BBR on SW480 cells. Our results revealed that BBR inhibited the proliferation and migration, as well as induced the apoptosis of SW480 cells, in a dose-dependent manner. BBR induced the dose-dependent inhibition of cell proliferation in HT-29 cells. BBR inhibited the expression of GRP78 and its localization on the cell surface. Moreover, BBR inhibited the expression of Bax, Bcl-2, c-Myc, and Vimentin and up-regulated the cytokeratin expression in SW480 cells. In addition, we found that the effects of BBR on cell proliferation, migration, and apoptosis in SW480 cells were reversed by the overexpression of GRP78. Our findings demonstrated that BBR inhibited the proliferation and migration and induced the apoptosis of SW480 cells by downregulating the expression of GRP78, and targeting GRP78 might be a potential way to develop the effective anticancer therapy.
Targeted therapy clinical trials in ovarian cancer: improved outcomes by gene mutation screening
Authors: Guo Quan , Yang Qing , Li Jun , Liu Guipeng , Nikoulin Igor , Jia Steve
Published: November 2019

Epithelial ovarian cancer is the most common and leading cause of death for gynaecologic cancer in the western world. Current standard treatments with limited selection of chemotherapies cannot meet patients’ urgent needs. Novel targeted therapies may improve patients’ survival rate with less side effects that have been demonstrated by using approved medicines such as poly ADP-ribose polymerase and angiogenesis inhibitors. Many classes of targeted therapies impacting cell signalling pathways related to ovarian cancer tumorigenesis have been investigated in clinical trial studies. Gene mutation screening is a powerful tool for improvement of success rate of the trials for better patient selection and interpretation of clinical outcomes. Increasing number of patients are being screened for genetic alterations particularly in ‘basket’ trials that are offering new, genetic-oriented therapies to patients. Thus, in this review, we have searched databases of Pubmed and Clinicaltrials.gov for the past and current phase III and selected phase II ovarian cancer clinical trials with focus on gene profiling. Lessons from both successful and failed trials and implications of ongoing trials are discussed.
A case of pelvic giant cell tumor of bone, complete remission with denosumab: long duration of response
Authors: Bilgetekin Irem , Mammadkhanli Orkhan , Basal Fatma Bugdayci , Kandemir Olcay , Canbay Suat , Oksuzoglu Berna
Published: November 2019

Although giant cell tumor of bone has been considered as a disease with benign course, it can lead to bone destruction and serious morbidity. A 19-year-old case was presented with hip pain. There was a recurrence after 9 months of curative surgical resection and zoledronic acid use, and as surgical morbidity would be high, antiosteoclastic receptor activator of nuclear factor kappa B ligand inhibitor denosumab treatment was administered. She had a complete remission after 18 months of denosumab treatment. The important point in the present case is that it has been followed up without recurrence after around 42 months of denosumab use and 11 months of follow-up after the cessation of drug. In recurrent cases in which nonmetastatic surgery is not suitable, the use of denosumab decreases tumor progression. The duration of use in unresectable and advanced cases still remains unclear.
Corticosteroids as Adjunctive Therapy in the Treatment of Influenza: An Updated Cochrane Systematic Review and Meta-analysis
Authors: Lansbury Louise E. , Rodrigo Chamira , Leonardi-Bee Jo , Nguyen-Van-Tam Jonathan , Shen Lim Wei
Published: November 2019

Objectives:

Corticosteroids may be beneficial in sepsis, but uncertainty remains over their effects in severe influenza. This systematic review updates the current evidence regarding corticosteroids in the treatment of influenza and examines the effect of dose on outcome.

Data Sources:

Electronic databases (MEDLINE, EMBASE, CINAHL, LILACS, CENTRAL, and Web of Science) and trial registries were searched to October 2018 for randomized controlled trials, quasi-experimental designs, and observational cohort studies reporting corticosteroid versus no corticosteroid treatment in individuals with influenza.

Study Selection and Data Extraction:

Two researchers independently assessed studies for inclusion. Risk of bias was assessed using the Cochrane Risk of Bias tool (randomized controlled trials) or Newcastle-Ottawa Scale (observational studies). Where appropriate, we estimated the effect of corticosteroids by random-effects meta-analyses using the generic inverse variance method. Meta–regression analysis was used to assess the association of corticosteroid dose and mortality.

Data Synthesis:

We identified 30 eligible studies, all observational apart from one randomized controlled trial. Twenty-one observational studies were included in the meta-analysis of mortality, which suggested an adverse association with corticosteroid therapy (odds ratio, 3.90; 95% CI, 2.31–6.60; 15 studies; adjusted hazard ratio, 1.49; 95% CI, 1.09–2.02; six studies). Risk of bias assessment was consistent with potential confounding by indication. Pooled analysis of seven studies showed increased odds of hospital-acquired infection in people treated with corticosteroids (unadjusted odds ratio, 2.74; 95% CI, 1.51–4.95). Meta-regression of the effect of dose on mortality did not reveal an association, but reported doses of corticosteroids in included studies were high (mostly > 40 mg methylprednisolone [or equivalent] per day).

Conclusions:

Corticosteroid treatment in influenza is associated with increased mortality and hospital-acquired infection, but the evidence relates mainly to high corticosteroid doses and is of low quality with potential confounding by indication a major concern.
Alive and Ventilator Free: A Hierarchical, Composite Outcome for Clinical Trials in the Acute Respiratory Distress Syndrome*
Authors: Novack Victor , Beitler Jeremy R. , Yitshak-Sade Maayan , Thompson B. Taylor , Schoenfeld David A. , Rubenfeld Gordon , Talmor Daniel , Brown Samuel M.
Published: November 2019

Objectives:

Survival from acute respiratory distress syndrome is improving, and outcomes beyond mortality may be important for testing new treatments. The “ventilator-free days” score, is an established composite that equates ventilation on day 28 to death. A hierarchical outcome treating death as a worse than prolonged ventilation would enhance face validity, but performance characteristics and reporting of such an outcome are unknown. We therefore evaluated the performance of a novel hierarchical composite endpoint, the Alive and Ventilator Free score.

Design:

Using data from four Acute Respiratory Distress Syndrome Network clinical trials, we compared Alive and Ventilator Free to the ventilator-free days score. Alive and Ventilator Free compares each patient with every other patient in a win-lose-tie for each comparison. Duration of mechanical ventilation is only compared if both patients survived. We evaluated power of Alive and Ventilator Free versus ventilator-free days score under various circumstances.

Setting:

ICUs within the Acute Respiratory Distress Syndrome Network.

Patients:

Individuals enrolled in four Acute Respiratory Distress Syndrome Network trials.

Interventions:

None for this analysis.

Measurements and Main Results:

Within the four trials (n = 2,410 patients), Alive and Ventilator Free and ventilator-free days score had similar power, with Alive and Ventilator Free slightly more powerful when a mortality difference was present, and ventilator-free days score slightly more powerful with a difference in duration of mechanical ventilation. Alive and Ventilator Free less often found in favor of treatments that increased mortality and increased days free of ventilation among survivors.

Conclusions:

A hierarchical composite endpoint, Alive and Ventilator Free, preserves statistical power while improving face validity. Alive and Ventilator Free is less prone to favor a treatment with discordant effects on survival and days free of ventilation. This general approach can support complex outcome hierarchies with multiple constituent outcomes. Approaches to interpretation of differences in Alive and Ventilator Free are also presented.
Family Care Rituals in the ICU to Reduce Symptoms of Post-Traumatic Stress Disorder in Family Members—A Multicenter, Multinational, Before-and-After Intervention Trial*
Authors: Amass Timothy H. , Villa Gianluca , OMahony Sean , Badger James M. , McFadden Rory , Walsh Thomas , Caine Tanis , McGuirl Don , Palmisciano Amy , Yeow Mei-Ean , De Gaudio Raffaele , Curtis J. Randall , Levy Mitchell M.
Published: November 2019

Objectives:

To assess the feasibility and efficacy of implementing “Family Care Rituals” as a means of engaging family members in the care of patients admitted to the ICU with a high risk of ICU mortality on outcomes including stress-related symptoms in family members.

Design:

Prospective, before-and-after intervention evaluation.

Setting:

Two U.S. academic medical ICU’s, and one Italian academic medical/surgical ICU.

Subjects:

Family members of patients who had an attending predicted ICU mortality of greater than 30% within the first 24 hours of admission.

Interventions:

A novel intervention titled “Family Care Rituals” during which, following a baseline observation period, family members enrolled in the intervention phase were given an informational booklet outlining opportunities for engagement in care of the patient during their ICU stay.

Measurements and Main Results:

Primary outcome was symptoms of post-traumatic stress disorder in family members 90 days after patient death or ICU discharge. Secondary outcomes included symptoms of depression, anxiety, and family satisfaction. At 90-day follow-up, 131 of 226 family members (58.0%) responded preintervention and 129 of 226 family members (57.1%) responded postintervention. Symptoms of post-traumatic stress disorder were significantly higher preintervention than postintervention (39.2% vs 27.1%; unadjusted odds ratio, 0.58; p = 0.046). There was no significant difference in symptoms of depression (26.5% vs 25.2%; unadjusted odds ratio, 0.93; p = 0.818), anxiety (41.0% vs 45.5%; unadjusted odds ratio, 1.20; p = 0.234), or mean satisfaction scores (85.1 vs 89.0; unadjusted odds ratio, 3.85; p = 0.052) preintervention versus postintervention 90 days after patient death or ICU discharge.

Conclusions:

Offering opportunities such as family care rituals for family members to be involved with providing care for family members in the ICU was associated with reduced symptoms of post-traumatic stress disorder. This intervention may lessen the burden of stress-related symptoms in family members of ICU patients.
A Case of Triple-Negative Myasthenia Gravis Lambert-Eaton Overlap Syndrome With Negative Agrin and LRP-4 Antibodies
Authors: Maturana Miguel A. , Bertorini Tulio E. , Mei Lin , Pandhi Abhi , Mays William H.
Published: November 2019

A case of triple-negative myasthenia gravis Lambert-Eaton overlap syndrome with negative Agrin and LRP-4 antibodies. Myasthenia gravis (MG) is an autoimmune disorder that shares similar features with Lambert-Eaton myasthenic syndrome. The combined clinical and electrophysiological findings of MG and Lambert-Eaton myasthenic syndrome have been reported, these cases represent the so-called “myasthenia gravis Lambert-Eaton overlap syndrome” (MLOS). A total of 55 MLOS cases have been identified, 13 cases were reported before the acetylcholine receptor (AChR) antibody (ab) testing era, 14 during the AChR-ab era, 26 during the voltage-gated calcium channel (VGCC)-ab era, and 2 cases have been reported during the muscle-specific kinase (MuSK)-ab era, of these; only 1 patient tested negative for all 3 antibodies. New immunological markers have been identified in the study of MG [Agrin and the low-density lipopro-tein receptor-related protein 4 (LRP-4)]. We present a patient with MLOS who tested negative for all 5 (AChR, MuSK, VGCC, Agrin, and LRP-4) serologic markers.
What Is in the Literature
Authors: Bromberg Mark B.
Published: November 2019

This installment of what is in the literature is on amyotrophic lateral sclerosis (ALS). The pathophysiology of ALS remains open and the role of genes, a foothold into pathophysiology, but there are >22 genes identified, and the mechanisms are not known for any. Despite the lack of a firm understanding of pathophysiology, drug trials continue based on possible mechanisms, but no new drugs beyond riluzole and edaravone have been positive in phase 3 trials. There are a number of formal stem cell trials underway, and the results of a phase 2 trial are described. Major efforts to make trials more sensitive are being considered. There are a number of articles with helpful and practical findings for the diagnosis and management of ALS.
Monozygotic Twins Discordant for Kennedy Disease: A Case Report
Authors: Popescu Cyprian
Published: November 2019

Spinal and bulbar muscular atrophy or Kennedy disease (KD) is an X-linked recessive disorder caused by a pathogenic CAG expansion in the first exon of the androgen receptor. Proximal muscle atrophy, weakness, contraction fasciculations, bulbar involvement, and sensory disturbances are part of the clinical picture of KD. We report the unusual genetic and phenotypic expression in 2 monozygotic twins. Genetic analysis has shown abnormal expansion of CAG repeat in the first exon of the androgen receptor gene on chromosome X different between the twin brothers (44, respectively, 46) but with large phenotypical differences including onset age, evolution, and clinical features. Disease began at age 31 for the first brother, respectively, and at 56 years for the second one and consisted of muscle wasting and progressive impairment of walking. In addition, the second brother did not manifest bulbar involvement 3 years after clinical onset and has more sensory features. Besides classical EMG testing, we evaluate sensory participation in spinal and bulbar muscular atrophy with sudoscan device and confirmed the sensory deficit. We discussed epigenetic factors potentially involved in KD that could play a role in the phenotypical differences. To the best of our knowledge, this is the first case describing CAG trinucleotide repeats in monozygotic twins and also the first sudoscan diagnostic of sensory disturbances in Kennedy syndrome.
Distal Cervical Spondylotic Amyotrophy: Case Reports Demonstrating Clinical/Imaging Segmental Discrepancy
Authors: Bourque Pierre R. , Mobach Theo , Warman-Chardon Jodi , Breiner Ari
Published: November 2019

Monomelic pure motor amyotrophy may seem to be an ominous syndrome as it leads to consideration of motor neuron disease. We present a series of 3 very similar cases where unilateral pure distal lower motor neuron paresis and atrophy was limited to the C8-T1 myotomes, without long-tract signs. Electrodiagnostic studies were in keeping with a restricted anterior horn cell disorder. Neuroimaging showed very focal spinal cord compression at the C6-7 level. Two patients underwent surgical decompression. All 3 patients were improved or stable at follow-up. Distal spondylotic amyotrophy is characterized by equal involvement of thenar and hypothenar muscles, in contrast to amyotrophic lateral sclerosis or Hirayama disease. We discuss the striking 2-level discrepancy between imaging and clinical localization. Proposed explanations are arterial or venous compromise caudal to the site of compression. Anatomical variation such as a prefixed brachial plexus is unlikely. A similar imaging/clinical discrepancy has been documented in Hirayama disease and spondylotic myelopathy.
Significance of Asymptomatic Hyper Creatine-Kinase Emia
Authors: Finsterer Josef , Scorza Fulvio A. , Scorza Carla A.
Published: November 2019

Objectives:

Whether asymptomatic hyper-CKemia (AHCE) should prompt a thorough work-up for muscle disease or not is controversially discussed. This review aims at summarizing and discussing recent findings concerning the cause, frequency, evolution, and work-up of conditions manifesting as AHCE and normal or abnormal electromyography (EMG) respectively muscle biopsy.

Methods:

Systematic PubMed search.

Results:

There are numerous primary (hereditary) and acquired myopathies that manifest with permanent, recurrent, or temporary AHCE with/without myopathic EMG or muscle biopsy. AHCE particularly occurs at onset of these conditions, which include dystrophinopathies, myotilinopathies, calpainopathy, caveolinopathy, dysferlinopathy, central core disease, multicore disease, desminopathy, MD1, MD2, hypoPP, malignant hyperthermia susceptibility, Pompe disease, McArdle disease, myoadenylate deaminase-deficiency, CPT2-deficiency, mitochondrial disorders, or myopathy with tubular aggregates. Most likely, other primary myopathies manifest with AHCE as well, without having been reported. Patients with AHCE should be taken seriously and repeated CK determination must be conducted. If hyper-CKemia is persisting or recurrent, these patients should undergo an EMG and eventually muscle biopsy. If noninformative, genetic work-up by a panel or whole exome sequencing should be initiated, irrespective of the family history. Patients with AHCE should avoid excessive exercise, require sufficient hydration, require counseling with regard to the risk of malignant hyperthermia, and should inform anesthesiologists and surgeons about their condition before elective surgery.

Conclusions:

Recurrent AHCE should be taken seriously and managed with conventional work-up. If noninformative, genetic work-up should follow irrespective of the family history.
Oculopharyngeal Muscular Dystrophy, an Often Misdiagnosed Neuromuscular Disorder: A Southern California Experience
Authors: Goyal Namita A. , Mozaffar Tahseen , Chui Luis A.
Published: November 2019

Objective:

Oculopharyngeal muscular dystrophy (OPMD) is a rare neuromuscular disorder characterized by late-onset development of bilateral eyelid ptosis, ophthalmoparesis and dysphagia with further progression to proximal limb muscle weakness that is an under recognized condition. The mode of inheritance is usually autosomal dominant, but a recessive form has been reported. OPMD is caused by a short expansion of the alanine repeat (GCN trinucleotide) in the poly(adenylate)-binding protein nuclear1 (PABPN1) gene.

Methods:

We performed a retrospective review of undiagnosed cases that initially presented with ptosis, diplopia, dysphagia, muscle weakness, muscular dystrophy and/or myasthenia gravis from 2000 to 2015 at two institutions in Southern California.

Results:

Twenty-five patients were identified to have OPMD with genetic confirmation.

Conclusions:

Even though a rare condition, the prevalence is disproportionally frequent in certain ethnic groups and in certain regions; thus, we report our experience of OPMD patients in Southern California.
Mohs Micrographic Surgery for the Treatment of External Ear Melanoma: an Outcome Study
Authors: Puyana Carolina , Ham Paula , Tsoukas Maria M.
Published: November 2019

BACKGROUND

The external ear is composed of thin skin overlying cartilage making melanoma on the external ear difficult to resect while preserving the intricate anatomy. Although surgeons have achieved robust clinical outcomes for nonmelanoma and most recently melanoma skin cancers with Mohs micrographic surgery (MMS), there is still not enough evidence on the MMS application for external ear melanoma treatment.

OBJECTIVE

The authors examined survival outcomes in patients treated with MMS, narrow margin excision (NME), and wide margin excision (WME) for melanoma on the external ear.

METHODS

Data from the NCI SEER program was retrospectively analyzed. Patients who received surgical treatment on the external ear and had microscopically confirmed diagnosis of cutaneous melanoma were included in the study. The effect of different surgery types: MMS, NME, and WME, on melanoma survival was evaluated.

RESULTS

A total of 8,212 melanoma cases of the external ear performed during the years 2000 to 2015 were considered for analysis. There were no significant differences in survival comparing NME and WME with MMS.

CONCLUSION

Mohs micrographic surgery is at least equivalent to WME for the treatment of melanoma of the external ear.
Update and Review of Bleeding Considerations in Dermatologic Surgery: Anticoagulants and Antiplatelets
Authors: Iyengar Sanjana , Yeager Danielle G. , Cohen Joel L. , Ozog David M.
Published: November 2019

BACKGROUND

Bleeding is an unavoidable risk of dermatologic surgery. The risk may be higher in patients taking agents that affect hemostasis.

OBJECTIVE

The aim of this study was to provide an updated review of current anticoagulant and antiplatelet therapy available in the market and their associated risk of bleeding complications in cutaneous surgery.

MATERIALS AND METHODS

A review of PubMed and MEDLINE was performed to review the English-language medical literature.

RESULTS

Many anticoagulant and antiplatelet therapies exist. Several studies recommend the continued use of antiplatelet and anticoagulant medications in the perioperative period. Combination regimens and novel oral anticoagulants may be associated with an increased risk of bleeding.

CONCLUSION

An updated understanding of antiplatelet and anticoagulant agents is critical for the surgeon. Current evidence does not support the discontinuation of antiplatelet and anticoagulant agents in the perioperative period under most circumstances. However, relevant data on novel oral anticoagulant agents are still sparse, suggesting that a precautionary approach is warranted.
Depth Map for Face and Neck Deep Chemical Peel Resurfacing
Authors: Sterling J. Barton , Lee Kachiu C. , Wambier Carlos G. , Soon Seaver L. , Landau Marina , Rullan Peter P. , Brody Harold J.
Published: November 2019

BACKGROUND

Chemical peels are applied to the face and neck to improve rhytides and the photoaged appearance of the skin. Peels can be applied to different skin depths depending on the types of chemicals, the volume of solution, and the amount of pressure or friction applied. If a peel is applied too superficially, rhytides will not be removed. If a peel is applied too deeply, scarring or hypopigmentation could occur.

OBJECTIVE

To create face and neck depth maps for chemical peeling, which can guide safety when removing rhytides and improving the skin's appearance.

MATERIALS AND METHODS

A multicenter retrospective review of records was conducted of patients who underwent phenol–croton oil peeling, from January 1, 2018, to December 31, 2018. Information was collected on facial and neck cosmetic units peeled, peel formula and strength used, outcomes, and complications.

RESULTS

A total of 410 patients received deep peels. Two depth maps were created that corresponded to the most common patterns of deep chemical peel applications.

CONCLUSION

Different areas of the face and neck are treated with different chemical peel application depths to safely improve rhytides and appearance. Depth maps are created to balance safety and efficacy.
Point of View: Electrophysiological Endpoints Differ When Comparing the Mode of Action of Highly Successful Anti-arrhythmic Drugs in the CAVB Dog Model With TdP
Authors: van Weperen Valerie Y. H. , Bossu Alexandre , Vos Marc A.
Published: November 2019

In the anaesthetized, chronic atrioventricular block (CAVB) dog, ventricular ectopic beats and Torsade de pointes arrhythmias (TdP) are believed to ensue from an abrupt prolongation of ventricular repolarization and increased temporal dispersion of repolarization, quantified as short-term variability (STV). These TdP stop spontaneously or, when supported by substantial spatial dispersion of repolarization (SDR), degenerate into ventricular fibrillation. However, most studies involving ventricular arrhythmias do not quantify SDR by means of an electrophysiological parameter. Therefore, we reviewed the effects of 4 highly effective anti-arrhythmic drugs (flunarizine, verapamil, SEA-0400, and GS-458967) on the repolarization duration and associated STV. All drugs were tested as anti-arrhythmic strategies against TdP in CAVB dogs, their high anti-arrhythmic efficacy was defined as suppressing drug-induced TdP in 100% of the experiments. This comparison demonstrates that even though the anti-arrhythmic outcome was similar for all drugs, distinct responses of repolarization duration and associated STV were observed. Moreover, the aforementioned and commonly adopted electrophysiological parameters were not always sufficient in predicting TdP susceptibility, and additional quantification of the SDR proved to be of added value in these studies. The variability in electrophysiological responses to the different anti-arrhythmic drugs and their inconsistent adequacy in reflecting TdP susceptibility, can be explained by distinct modes of interference with TdP development. As such, this overview establishes the separate involvement of temporal and spatial dispersion in ventricular arrhythmogenesis in the CAVB dog model and proposes SDR as an additional parameter to be included in future fundamental and/or pharmaceutical studies regarding TdP arrhythmogenesis.
Sulodexide Improves Contraction and Decreases Matrix Metalloproteinase-2 and -9 in Veins Under Prolonged Stretch
Authors: Raffetto Joseph D. , Yu Wentao , Wang Xi , Calanni Fiorella , Mattana Paolo , Khalil Raouf A.
Published: November 2019

High pressure in the lower-limb veins is often associated with chronic venous insufficiency and varicose veins (VVs), making it important to search for the mechanisms and agents that control venous function. We have shown that protracted increases in venous stretch/wall tension reduce vein contraction and augment matrix metalloproteinase (MMP)-2 and -9. Also, MMP-2 and MMP-9 promote venodilation, a hallmark of VVs. Sulodexide (SDX) is a blend of glycosaminoglycans with efficient profibrinolysis and antithrombosis activities, but its actions on vein function and the mechanisms involved are unclear. We tested the hypothesis that SDX enhances venous contractile response by decreasing MMP expression/activity in veins subjected to protracted stretch. Rat inferior vena cava (IVC) rings were treated with SDX (0.001–1 mg/mL) or vehicle, equilibrated under control 0.5-g resting tension or protracted 2-g stretch for 18 hours, and the contractile response to 96-mM KCl and phenylephrine (Phe) in SDX-treated and nontreated veins was recorded. In IVC rings under control 0.5-g resting tension, SDX caused dose-dependent contraction, 96-mM KCl caused marked contraction (176-mg/mg tissue), and Phe caused dose-dependent contraction with a maximum (56-mg/mg tissue) at 10−5 M. In IVC subjected to protracted 2-g stretch, 96-mM KCl-induced contraction was reduced to 112 mg/mg and maximal Phe-induced contraction was decreased to 23 mg/mg. In IVC subjected to protracted 2-g stretch plus SDX, 96-mM KCl-induced contraction was restored to 228 mg/mg and maximal Phe-induced contraction was improved to 115 mg/mg. Gelatin zymography and Western blots revealed increases in MMP-2 and MMP-9 levels/gelatinolytic activity in veins subjected to protracted 2-g stretch and reversal to control levels in veins subjected to 2-g stretch plus SDX. Thus, SDX improves vein function and augments the contractile response in veins subjected to protracted stretch. The SDX-induced improvement of contraction and restoration of vein function appear to involve decreases in MMP-2 and MMP-9 and may contribute to the benefits of SDX in chronic venous insufficiency and VVs.
Management of Recessive Dystrophic Epidermolysis Bullosa in a Newborn with Porcine-derived Extracellular Matrix
Authors: Le Nicole K. , Billington Alicia , Harrington Michael , Seminario-Vidal Lucia
Published: November 2019

Epidermolysis bullosa is a debilitating dermatologic disorder affecting the adhesive capability between the epidermis and dermis. The severe recessive dystrophic variant is caused by mutations in COL7A1, the gene encoding type VII collagen which is the major structural protein of the anchoring fibrils linking these 2 skin layers.1 The management of recessive dystrophic epidermolysis bullosa (RDEB) remains complex with no curative therapy. We present herein the novel use of a porcinederived extracellular matrix dressing to effectively treat extensive erosions in a newborn.
Gallbladder and Biliary Disease in Pregnancy
Authors: BROWN KRISTINE E. , HIRSHBERG JONATHAN S. , CONNER SHAYNA N.
Published: November 2019

Diseases of the gallbladder and biliary tract are extremely common in developed nations. Because of the physiology of pregnancy, their incidence increases during gestation. This article represents a review of the existing literature on the entire spectrum of biliary disease. The physiology, clinical presentation, and diagnostic evaluation of a variety of conditions are reviewed. Historical and contemporary data regarding pregnancy implications and treatment options are discussed.
Treatment of Anemia in Transfusion-Dependent and Non-Transfusion-Dependent Lower-Risk MDS: Current and Emerging Strategies
Authors: Germing Ulrich , Oliva Ester N. , Hiwase Devendra , Almeida Antonio
Published: November 2019

Myelodysplastic syndromes (MDS) are a heterogeneous group of bone marrow disorders with a highly diverse clinical course. For lower-risk MDS patients, therapeutic objectives aim to correct chronic anemia and improve/maintain health-related quality of life (HRQoL). However, disease burden is often insufficiently recognized, and although some patients do not respond/lose response to standard treatment, many are treated late. This is the case for non-transfusion-dependent patients with symptomatic anemia, in whom delayed treatment initiation may lead to unnecessary morbidity. Current active treatment options for lower-risk MDS are limited. Standard care for lower-risk 5q deletion [del(5q)] MDS patients with anemia remains supportive, consisting of red blood cell (RBC) transfusions, iron chelation therapy, and treatment with erythropoiesis-stimulating agents (ESAs) in the case of low serum erythropoietin levels. Response rates to ESAs range from 15% to 63%, whereas 56% to 67% of patients with del(5q) MDS achieve RBC transfusion independence with lenalidomide. Treatment options for patients’ refractory to ESAs and/or lenalidomide, however, are limited. Frequent transfusions are associated with profound clinical, HRQoL, and economic consequences for transfusion-dependent patients. This review focuses on the multiple unmet clinical needs that exist in the treatment of anemia associated with lower-risk MDS and the current and future treatment options that may improve disease management and patient outcomes.
Is Acute Myeloblastic Leukemia in Children Under 2 Years of Age a Specific Entity? A Report from the FRENCH ELAM02 Study Group
Authors: Blais S. , Boutroux H. , Pasquet M. , Leblanc T. , Fenneteau O. , Gandemer V. , Bertrand Y. , Ducassou S. , Michel G. , Nelken B. , Petit A. , Cuccuini W. , Gouache E. , Renaut Marceau-A. , Baruchel A. , Lapillonne H. , Leverger G.
Published: November 2019

The clinical and biological characteristics of children under 2 years (infants) with acute myeloid leukemia (AML) are different from those of older children. We aimed to describe the specific characteristics of this population and the potential factors that influence the prognosis. We analyzed data concerning 438 children with newly-diagnosed AML treated in the ELAM02 protocol between March 2005 and December 2011, of which 103 were under 2 years old at diagnosis. The evaluation criteria were overall survival (OS) and event-free survival (EFS) of infants vs older children. The clinical and biological features were secondary criteria. Infants presented more frequent extra-medullary presentation than older children. They had a significantly higher proportion of skin lesions and central nervous system involvement (15% vs 3%, p < 0.0001 and 26% vs 12%, p = 0.0005, respectively). The global incidence of KMT2A rearrangements was nearly 55% for infants vs 11% for older children (p < 0.0001). Median 5-year OS was 70.4% for infants vs 71.4% for older children (p = 0.83). Five-year EFS was 67% for infants vs 58% for older children (p = 0.27). Infants with AML represent a cohort of patients with specific clinical and biological features. These remarkable differences had no significant impact on their outcome in the ELAM02 protocol.
Histologic Evaluation of Nonvisual Afferent Sensory Upper Eyelid Proprioception
Authors: Vrcek Ivan , Blumer Roland , Blandford Alex , Somogyi Marie , Durairaj Vikram , Blaydon Sean , Shore John , Amato Malena , Nakra Tanuj
Published: November 2019

The authors describe proprioception in the upper eyelid: A histologic analysis.

Purpose:

Recent research has suggested a possible role for proprioception in ipsilateral frontalis activation in the setting of ptosis; however, there has not been any robust histologic or anatomic evidence to support this theory. To further elucidate proprioceptive structures in the eyelid, this investigation uses validated histologic techniques to explore the presence of proprioceptive structures or afferent neural networks in the Levator Palpebrae Superioris (LPS) and Müller muscle.

Methods:

Müller muscle and LPS samples were evaluated by a laboratory with extensive experience with the histology of extraocular muscle proprioception. Immunofluorescence and confocal laser scanning microscopy were used to analyze the tissue samples.

Results:

Thirty-four Müller muscle samples and 10 LPS samples were analyzed. Golgi tendon bodies and muscle spindles were not identified in the Müller muscle and LPS samples. This result is expected in the Müller muscle given that these structures are not typically present in smooth muscle, but noteworthy in the skeletal muscle of the LPS. Previously undescribed synaptophysin-positive free nerve terminals within the intermuscular connective tissue of the Müller muscle were identified.

Conclusions:

The nerve terminals identified are anatomically consistent with free nerve endings present in the extraocular muscles that have been implicated in proprioception. These findings advance our current knowledge of the ultrastructure of Müller muscle and the LPS and suggest a possible mechanism for proprioception in the upper eyelid that may have a role in ipsilateral brow elevation in the setting of ptosis.
Long-Term Outcomes of StopLoss Jones Tubes for Epiphora in Patients With Early or Multiple Loss of Lester Jones Tubes
Authors: Timlin Hannah M. , Jiang Kailun , Mathewson Priscilla , Manta Alexandra , Rubinstein Tal , Ezra Daniel G.
Published: November 2019

Purpose:

Extrusion is the most common cause of failure in conventional Lester Jones tubes (LJTs). StopLoss Jones tubes (SLJTs) with distal flange are designed to reduce this complication. This study compared the survival of SLJTs with their prior LJTs and control patients with LJTs-only.

Methods:

Retrospective review of consecutive LJT or SLJT insertion between January 2014 and December 2016.

Results:

Twenty-eight eyes of 23 patients had 31 SLJTs. Before their SLJTs, these patients had 116 cumulative failed LJTs. Forty-seven eyes of 34 patients had 59 LJTs only. Fifty-two percent of SLJT group and 18% of LJT-only group had complex medial canthal conditions (p = 0.003). Compared to their previous LJTs, the SLJTs were less likely to extrude (3% SLJT vs. 64% prior LJT, p < 0.0001); there was no statistical difference in rates of sinking in (26% SLJT vs. 13% prior LJT, p = 0.0964). The median survival of LJTs in those who went on to have a SLJT was 3.5 months. SLJT insertion significantly lengthened the median survival to 26 months (p < 0.0001), comparable to the LJT-only group (25.5 months, p = 0.45). While extrusion was also the most common complication in the LJT-only group, this occurred only in 20% of eyes; tube failure from sink-in occurred in 14% of eyes.

Conclusions:

SLJTs, in patients prone to multiple or early prior LJT losses, can be used to rescue this group and allow them to regain a similar survival curve to the less complicated LJT-only group. Rates of tube extrusion are significantly reduced with the use of SLJT.
The Effect of Canthotomy on Blood Perfusion During the Repair of Lower Eyelid Defects
Authors: Berggren Johanna V. , Tenland Kajsa , Memarzadeh Khashayar , Sheikh Rafi , Hult Jenny , Lindstedt Sandra , Malmsjö Malin
Published: November 2019

Purpose:

Canthotomy is frequently used to mobilize extra tissue when repairing larger lower eyelid defects. The aim of this study was to explore the effect of canthotomy on blood perfusion and oxygen tension.

Methods:

Eight pigs underwent a wedge resection of the lower eyelid and canthotomy (with cantholysis involving the lateral palpebral artery). The wedge resection was performed 8, 6, and 4 mm from the canthotomy. Perfusion and oxygen tension were monitored in the eyelid between the wedge resection and canthotomy using laser Doppler velocimetry and a Clark electrode. Verapamil was administered, and measurements were also performed 12 hours after surgery, to investigate the possible effects of vasospasm

Results:

The wedge resection alone did not affect perfusion. Canthotomy led to a reduction in perfusion; being 60% when the length of remaining eyelid was 8 mm, 32% when it was 6 mm, and 24% when it was 4 mm. Similar results were observed for oxygen tension. Vasospasm did not affect the results.

Conclusions:

Canthotomy in combination with a wedge resection of the lower eyelid affects blood perfusion. A smaller length of remaining eyelid tissue will have less perfusion. This may not have any implications in cases of direct closure, but may play a role when the eyelid is to provide oxygen and nutrients to avascular grafts.
Intracapsular High-Grade Ductal Carcinoma In-Situ Ex Pleomorphic Adenoma of the Lacrimal Gland
Authors: Garakani Roya , Kersten Robert , Pekmezci Melike
Published: November 2019

Primary ductal adenocarcinoma of the lacrimal gland is an aggressive neoplasm and can be seen either as a de novo malignancy or in the setting of a carcinoma ex pleomorphic adenoma. Carcinoma ex pleomorphic adenoma carries an overall unfavorable outcome; however, prognosis depends on the type and grade of the malignant component, presence of retained myoepithelial component, and extend of invasion beyond the capsule. Herein, the authors describe a 78-year-old man diagnosed with an incidental, intracapsular, high-grade ductal adenocarcinoma in situ ex pleomorphic adenoma, who is free of disease at 9 months subsequent to complete resection. It is important to recognize the morphologic features of intraductal and intracapsular neoplasms to prevent unnecessary morbidities due to extensive surgical interventions or radiotherapy.

Morphologic features of intracapsular ductal carcinoma in situ ex pleomorphic adenoma, which shows better clinical outcomes with complete excision than its invasive counterpart.
Temporal Fat Pad Volume in Patients With Thyroid Eye Disease
Authors: Choudhary Maria M. , Zhang Kevin R. , Johnson Scott , Hwang Catherine J. , Chon Brian H. , Perry Julian D.
Published: November 2019

Purpose:

To determine whether thyroid eye disease (TED) is associated with a change in temporal fossa soft tissue volume.

Methods:

CT imaging studies were selected from patients with TED considering orbital decompression surgery and from an age-matched group of controls presenting to the Emergency Department for nontraumatic conditions requiring CT imaging. Measurements of the temporal fossa fat pad and soft tissue thickness were used as a proxy for volume and were performed using the zygomaticotemporal suture as a reference point. Categorical variables were described using frequencies and percentages, while continuous variables were described using medians and standard deviations. Chi-square tests were used to assess the relationship between gender and age group, while t-tests were used to examine the relationship between continuous variables and age group.

Results:

A total of 56 CT scans were evaluated, including scans from 28 patients with TED and 28 controls. The following measurements were found to be significantly larger in the TED population: left fat pad measured 5 mm above the zygomaticotemporal suture (p = 0.012), right fat pad measured 15 mm above the suture (p = 0.005), right soft tissue measured 15 mm above the suture (p = 0.026), left fat pad measured 15 mm above the suture (p = 0.006), and the left soft tissue measure 15 mm above the suture (p = 0.032).

Conclusions:

Thyroid eye disease is associated with an increase in temporal fossa fat pad and soft tissue volume. These findings suggest that TED disease may produce pan-facial changes rather than changes confined to the peri-orbital region.
Calcitonin Gene-Related Peptide in Blind, Painful Eyes
Authors: Godbout Erin E. , Lau Kevin W. , Adam Alejandro P. , Wladis Edward J.
Published: November 2019

Purpose:

To determine if calcitonin gene-related peptide (CGRP) is overexpressed in blind, painful eyes.

Methods:

This was a retrospective cross-sectional randomized control study conducted at a tertiary level hospital. Eight specimens of eyes enucleated by a single surgeon were included in the study. The control group patients underwent exenteration for cutaneous malignancy without intraocular involvement, while the case group was enucleated for management of blind, painful eye. Each eye was stained using immunohistochemistry for the expression of CGRP. Expression of CGRP was examined by counting the number of cells staining positive for CGRP in 5 consecutive ×40 fields in the choroid, iris, and cornea of each specimen.

Results:

The mean number of cells staining positively for CGRP in the choroid of blind, painful eye group was 45.5 (26.3) versus 5.5 (7.7) in nonpainful enucleated eyes. This difference was found to be statistically significant (p = 0.016). Comparison of iris and cornea did not reach statistical significance. Expression of CGRP was compared using a paired t test.

Conclusions:

This study demonstrates that CGRP is overexpressed in the choroid of enucleated blind, painful eyes. Modulation of this protein may represent a meaningful, nonsurgical therapeutic strategy to addressing the blind, painful eye.
The Mathematical Analysis of the Aesthetically Pleasing Eyelid
Authors: McDonnell Emma C. , Patel Sagar Y. , Scofield-Kaplan Stacy M. , Chaulk Alexandria , Stetler Jeffrey , Starks Victoria , Mancini Ronald
Published: November 2019

Purpose:

To analyze and quantify the characteristics and parameters of the eyelid and adnexa of males and females and correlate these findings to an aesthetically pleasing score.

Methods:

This is an Institutional Review Board approved study involving healthy male and female volunteers. The margin-to-reflex distance, palpebral fissure, inferior scleral show, tarsal platform show, and brow fat span were measured using Image J digital photographic analysis and the images were scored by 110 non-ophthalmologists. The eyelid parameters were compared between the groups with Student t tests and the total aesthetic score was correlated to the measured parameters with Pearson’s correlation coefficients (r). This study was HIPAA-compliant with protection of individually identifiable information.

Results:

Twenty male and 22 female participants were included and divided into 2 groups based on the aesthetic score. The average aesthetic score was 3.06 for males and 3.36 for females. None of the eyelid parameters were found to be significantly significant between the 2 male groups. In females, both inferior scleral show and tarsal platform show were significantly lower in the more aesthetic group. A greater margin-to-reflex distance correlated with increased aesthetic appeal. The ratio of brow fat span/tarsal platform show was not significantly different between the 2 female groups.

Conclusions:

Quantifying goals are important for the surgical and nonsurgical management of the eyelid and periorbita. Beauty is considered to be subjective and is comprised of various criteria. However, this study reveals that the female sex may have certain quantifiable goals for eyelid parameters that are considered more aesthetically pleasing.