bluuebunny/crossref_metadata_2025 huggingface dataset:
Microsurgical Clip Placement for a Giant Anterior Communicating Artery Aneurysm With Intraluminal Thrombus: 2-Dimensional Operative Video
Authors: Riechelmann Guilherme Salemi , da Costa Marcos Devanir Silva , Caramanti Ricardo Lourenço , Goiri Marcelo Augusto Acosta , Costa Bruno Lourenço , González-Echeverría Kléber , Chaddad-Neto Feres
Published: August 2018

Giant brain aneurysms account for approximately 5% of all intracranial aneurysms. Although treatment modalities can vary widely, none is ideal for every patient. Endovascular treatment is usually preferred, especially when the large size of the aneurysm limits visualization of the brain parenchyma and parent vessels that arise from the aneurysm, making surgical clip placement across the neck a difficult task. However, despite the higher chances of morbidity, microsurgery is an effective treatment modality due to lower recurrence rates. Surgically, a wide neck, calcifications, or atheroma are complicating factors to be considered while planning the best treatment. Thus, with an appropriate case selection, a favorable outcome is feasible in most cases. Here, we present the case of a 27-yr-old female who presented with a severe headache for 7 mo and 3 mo of progressive left temporal vision loss, which was confirmed by visual field perimetry using the Humphrey visual field analyzer. Magnetic resonance angiography and digital subtraction cerebral angiography showed an anterior communicating artery complex inferiorly and medially oriented aneurysm measuring 25.4 × 16.5 mm, with a 3 mm neck. It was fed by the right A1, associated with a hypoplastic left A1, incorporating the proximal right and left A2 segments, with an intraluminal thrombus and causing mass effect on the optic chiasm and hypothalamus. This video demonstrates the microsurgical steps required to perform this operation, through a right orbitozygomatic craniotomy. At a 3-mo follow-up, the patient was neurological intact without complaints.

 The patient signed the Institutional Consent Form, which allows the use of his/her images and videos for any type of medical publications in conferences and/or scientific articles.
Restored Self: A Phenomenological Study of Pain Relief by Cannabis
Authors: Lavie-Ajayi Maya , Shvartzman Pesach
Published: August 2018

Objective

To explore the subjective experience of pain relief by cannabis.

Design

Qualitative data were collected through in-depth semistructured interviews. Interview transcripts were analyzed using interpretative phenomenological analysis (IPA).

Subjects

Nineteen patients, aged 28 to 79, who were treated with medical cannabis under the supervision of a pain clinic in Israel.

Results

Three key themes that emerged from the analysis were explored: 1) the Sigh of Relief, describing the corporal sensation of using cannabis, including a sense of relaxation and reduction in pain; 2) the Return to Normality, describing the comprehensive effect of using cannabis, including an increased ability to sleep, focus, and function; and 3) the Side Effects of using cannabis.

Conclusions

We propose the term Restored Self to conceptualize the effect of medical cannabis. Restored Self is the experience of regaining one’s sense of self, sense of normality, and sense of control over one’s life.
Are Teaching Hospitals Treated Fairly in the Hospital-Acquired Condition Reduction Program?
Authors: Al Mohajer Mayar , Joiner Keith A. , Nix David E.
Published: August 2018

Purpose

To identify the factors associated with total Hospital-Acquired Condition Reduction Program (HACRP) score and with receiving a Centers for Medicare and Medicaid Services (CMS) penalty (1% reduction in payment to those hospitals in the lowest-performing quartile of HACRP scores) for fiscal years (FYs) 2015–2017 with a particular focus on trends over this period.

Method

The authors evaluated the following variables: (1) type of hospital (teaching vs. nonteaching); (2) disproportionate patient percentage; (3) case mix index (CMI); (4) number of staffed beds; (5) length of stay (LOS); (6) gross patient revenue; and (7) region, using data from CMS and the American Hospital Directory. They conducted multivariate linear and logistic regressions.

Results

A total of 2,249 hospitals were included. The mean total HACRP scores across hospitals for FY15, FY16, and FY17 were 5.38, 5.35, and 5.18, respectively. In FY15, 21.2% (476/2,249) of hospitals received a penalty compared with 22.6% (508/2,249) in FY16 and 31.3% (704/2,249) in FY17 (P < .001). The logistic regression model showed that teaching hospitals, larger hospitals (> 400 beds), hospitals with high CMI or long LOS, and hospitals in the Northeast and Western United States were more likely to receive a penalty. Teaching hospitals and larger hospitals did not improve their scores over time compared with nonteaching and small hospitals.

Conclusions

A reevaluation of the scoring methodology for the HACRP is needed. CMS could stratify hospitals into homogeneous categories and apply penalties to those that have the worst scores in each category.
Pharmacotherapy, Resource Needs, and Physician Recruitment Practices in Substance Use Disorder Treatment Programs
Authors: Knudsen Hannah K. , Brown Randy , Jacobson Nora , Horst Julie , Kim Jee-Seon , Collier Elizabeth , Starr Sanford , Madden Lynn M. , Haram Eric , Molfenter Todd
Published: August 2018

Objectives:

Effective pharmacological treatments for opioid use disorder (OUD) continue to be underutilized, particularly within specialty substance use disorder (SUD) treatment organizations. Few studies have examined whether specific practices to recruit prescribers, financial needs, and human resource needs facilitate or impede the implementation of pharmacotherapy.

Methods:

Surveys were completed by administrators from 160 treatment programs in Florida, Ohio, and Wisconsin. Respondents described availability of five pharmacotherapies for treating OUD, organizational resource needs, current use of physician recruitment practices, and buprenorphine treatment slots.

Results:

The mostly commonly available medications were injectable naltrexone (65.4%; n = 102), buprenorphine-naloxone (55.7%; n = 88), and tablet naltrexone (50.0%; n = 78). Adopters of each of the 5 pharmacotherapies reported significantly greater physician outreach than organizations that did not provide these medications. The mean number of buprenorphine slots was 94.1 (SD 205.9). There were unique correlates of adoption (ie, any slots) and availability (number of slots) of buprenorphine. Physician outreach activities were correlated with the likelihood of nonadoption, whereas medical resource needs (ie, needing more physicians to prescribe pharmacotherapy) and dedicated resources for physician recruitment were associated with the number of slots.

Conclusions:

Physician recruitment activities differentiated those organizations that had existing pharmacotherapy treatment capacity (ie, any slots) from those that had no capacity. Efforts to address the medical resource needs of treatment organizations, and also strategies that encourage organizations to devote resources to recruiting prescribers may hold promise for increasing access to these lifesaving treatments.
Addressing Workforce Needs for Medication Treatment of Opioid Use Disorder
Authors: Thomas Cindy Parks
Published: August 2018

Medication treatment of opioid use disorder (OUD) is recognized as an effective evidence-based treatment. It has been underused, in part due to challenges in recruiting and retaining a provider workforce that is able to prescribe and manage patients treated with OUD medications. A national goal should be: anyone with an OUD must have adequate access to a range of medications for treatment and support, provided in high-quality settings, and all programs receiving public or private funding should be so equipped. To accomplish this, it is important to understand what recruitment efforts are most successful, and what implementation strategies and service models are most effective. Building an adequate OUD treatment workforce, however, will require a system with adequate program resources and incentives, clinician and patient education to reduce stigma, limited regulatory burden, and adequate reimbursement and support high-quality services.
Nonmedical Use of Stimulants Is Associated With Riskier Sexual Practices and Other Forms of Impulsivity
Authors: Grant Jon E. , Redden Sarah A. , Lust Katherine , Chamberlain Samuel R.
Published: August 2018

Background:

This study sought to examine the occurrence of the nonmedical use of prescription stimulants (amphetamines and methylphenidate) in a university sample and their associated physical and mental health correlates, including potential relationships with risky sexual practices.

Methods:

A 156-item anonymous online survey was distributed via e-mail to a sample of 9449 university students. Current use of alcohol and drugs, psychological and physical status, and academic performance were assessed, along with questionnaire-based measures of impulsivity and compulsivity.

Results:

A total of 3421 participants (59.7% female) were included in the analysis. 6.7% of the sample reported current/recent nonmedical use of prescription stimulants, while an additional 5.8% reported misuse in the past. Nonmedical use of prescription stimulants was associated with lower grade point averages, and with taking a broad range of other drugs (including alcohol, nicotine, illicit substances, and consumption of caffeinated soft drinks). Nonmedical use of stimulants was also significantly associated with impulsivity (Barratt scale), prior treatment for substance use problems, and elevated occurrence of disordered gambling, post-traumatic stress disorder, and anxiety; but not depression symptoms or binge-eating disorder (though it was associated with using drugs to lose weight). The relationship with probable attention-deficit/hyperactivity disorder (ADHD) on screening was not significant but was numerically elevated. Finally, those using nonmedical prescribed stimulants were significantly more sexually active (including at a younger age), and were less likely to use barrier contraception.

Conclusions:

Nonmedical use of prescription stimulants is common in young adults and has profound public health associations including with a profundity of other drug use (licit and illicit), certain mental health diagnoses (especially gambling, anxiety, and post-traumatic stress disorder ), worse scholastic performance, and riskier sexual practices. The majority of people with nonmedical use of prescription stimulants do not have ADHD, and its link with current ADHD symptoms was less marked than for certain other disorders. Clinicians should screen for the misuse of prescription stimulants as they may be associated with a range of problematic behaviors. Risk of diversion (which may be higher for those living in shared accommodation and those with substance use disorder history) merits careful assessment before prescribing stimulant medication.
The Impact of Comorbidity Burden on Complications, Length of Stay, and Direct Hospital Costs After Minimally Invasive Transforaminal Lumbar Interbody Fusion
Authors: Khechen Benjamin , Haws Brittany E. , Bawa Mundeep S. , Patel Dil V. , Cardinal Kaitlyn L. , Guntin Jordan A. , Lalehzarian Simon P. , Singh Kern
Published: August 2018

Study Design.

A retrospective cohort.

Objective.

The aim of this study was to determine whether comorbidity as determined by Charlson Comorbidity Index (CCI) is associated with inpatient complication rate, length of stay (LOS), or direct hospital costs after minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF).

Summary of Background Data.

In the spine literature, comorbidity burden has been associated with an increased risk for complications, prolonged LOS, and greater hospital costs. Few studies have investigated the influence of comorbidity burden on these outcomes in minimally invasive spine surgery populations.

Methods.

A prospectively maintained surgical registry of patients undergoing primary, single-level MIS-TLIF was retrospectively reviewed. Patients were stratified by CCI and tested for association with preoperative demographics and perioperative characteristics using Chi-squared analysis or one-way analysis of variance for categorical and continuous variables, respectively. Complication rates, LOS, and direct hospital costs were compared between groups using a one-way analysis of variance.

Results.

Two hundred ninety-eight patients were included. About 19.8% had a CCI of 0, 41.3% had a CCI of 1 to 2, 27.2% had a CCI of 3 to 4, and 11.7% had a CCI ≥ 5. Elevated CCI was associated with older age, smoking, and insurance status. Elevated CCI was significantly associated with a greater total inpatient complication rate. Regarding LOS and total direct hospital costs, there were no associations identified. However, elevated CCI was associated with greater costs accrued in the intensive care unit, laboratory costs, and cardiology-related costs.

Conclusion.

Greater comorbidity burden as reflected by higher CCI was associated with increased postoperative complication rates following primary, single-level MIS-TLIF. However, this did not lead to prolongations in hospital stay or increased total direct hospital costs. This lack of association may suggest that the limited tissue trauma and operative exposure utilized in minimally invasive approaches may limit the utility of CCI as a predictor of surgical outcomes and costs.

Level of Evidence: 4
Postdischarge Major Adverse Cardiovascular Events of ICU Survivors Who Received Acute Renal Replacement Therapy
Authors: Park Sehoon , Lee Soojin , Kang Min Woo , Han Kyungdo , Kim Yaerim , An Jung Nam , Joo Kwon Wook , Lim Chun Soo , Kim Yon Su , Yoo Hai-Won , Kim Hyeongsu , Kim Dong Ki
Published: August 2018

Objectives:

Long-term risk of a major adverse cardiovascular events in ICU survivors who underwent acute renal replacement therapy requires further investigation.

Design:

Nationwide population-based study using the claims database of Korea.

Setting:

Index admission cases of ICU survivors in government-designated tertiary hospitals

Patients:

The study group consisted of ICU survivors who underwent acute renal replacement therapy, and the control group consisted of those without acute renal replacement therapy. Patients were excluded if they 1) were under age 20, 2) expired within 30 days after discharge, 3) received ICU care for less than 24 hours, 4) had a previous ICU admission, 5) had a history of major adverse cardiovascular event, or 6) had a major adverse cardiovascular event–related cardio/cerebrovascular diseases. The outcomes of the patients who received continuous renal replacement therapy were compared with those of patients who received only intermittent renal replacement therapy.

Interventions:

None.

Measurements and Main Results:

Information regarding patient characteristics and treatment modalities was collected and adjusted. The main outcome was major adverse cardiovascular event, including acute myocardial infarction, revascularization, and acute ischemic stroke. Patient mortality and progression to end-stage renal disease were also evaluated. We included 12,380 acute renal replacement therapy patients and 382,018 patients in the control group. Among the study group, 6,891 patients were included in the continuous renal replacement therapy group, and 5,034 in the intermittent renal replacement therapy group. The risks of major adverse cardiovascular event (adjusted hazard ratio, 1.463 [1.323–1.619]; p < 0.001), all-cause mortality (adjusted hazard ratio, 1.323 [1.256–1.393]; p < 0.001), and end-stage renal disease (adjusted hazard ratio, 18.110 [15.779–20.786]; p < 0.001) were higher in the acute renal replacement therapy patients than the control group. When we compared the continuous renal replacement therapy patients with the intermittent renal replacement therapy patients, the risk of major adverse cardiovascular event was comparable (adjusted hazard ratio, 1.049 [0.888–1.239]; p = 0.575).

Conclusions:

Clinicians should note the increased risk of a long-term major adverse cardiovascular event in acute renal replacement therapy patients and consider appropriate risk factor management. Significant difference in the risk of postdischarge major adverse cardiovascular event was not identified between continuous renal replacement therapy and intermittent renal replacement therapy.
Surgical skills assessment tools in gynecology
Authors: Clark Nisse V. , Pepin Kristen J. , Einarsson Jon I.
Published: August 2018

Purpose of review

The purpose of this review is to outline surgical skills assessment tools for the purpose of training and competency evaluation, with a focus on recent literature in gynecology.

Recent findings

Objective standardized surgical skills assessment tools are increasingly being explored in multiple surgical disciplines including gynecology. Several small studies in gynecology have validated procedure-specific checklists, global rating scales, and other surgical proficiency examinations in their ability to differentiate trainee skill level or correlate with other standardized tests. Few studies have included gynecologic surgeons in practice, and no studies have investigated their use in credentialing and maintenance of certification.

Surgical skills assessment tools may be a useful adjunct to gynecology training programs, with promising applications for practicing gynecologists.
How to Make Your Life Easier: Blepharoplasty Markings with Microsurgical Clamps
Authors: Ramella Vittorio , Stocco Chiara , Facchin Federico , Troisi Luigi , Papa Giovanni , Arnez Zoran Marij
Published: August 2018

Preoperative blepharoplasty markings might be challenging, especially for young surgeons. It takes experience to carefully evaluate the amount of skin excess that can be safely removed. In the current study, we explored the use of microsurgical vascular clamps as a novel and useful tool in the preoperative upper blepharoplasty markings; they made it possible to directly visualize the amount of skin to be removed, facilitating the surgeon (especially the young surgeon) preoperative markings process. In our series, 30 patients underwent upper blepharoplasty with preoperative application of microvascular clamps with satisfactory results.
Squid Ring Teeth–coated Mesh Improves Abdominal Wall Repair
Authors: Leberfinger Ashley N. , Hospodiuk Monika , Pena-Francesch Abdon , Ayan Bugra , Ozbolat Veli , Koduru Srinivas V. , Ozbolat Ibrahim T. , Demirel Melik C. , Ravnic Dino J.
Published: August 2018

Background:

Hernia repair is a common surgical procedure with polypropylene (PP) mesh being the standard material for correction because of its durability. However, complications such as seroma and pain are common, and repair failures still approach 15% secondary to poor tissue integration. In an effort to enhance mesh integration, we evaluated the applicability of a squid ring teeth (SRT) protein coating for soft-tissue repair in an abdominal wall defect model. SRT is a biologically derived high-strength protein with strong mechanical properties. We assessed tissue integration, strength, and biocompatibility of a SRT-coated PP mesh in a first-time pilot animal study.

Methods:

PP mesh was coated with SRT (SRT-PP) and tested for mechanical strength against uncoated PP mesh. Cell proliferation and adhesion studies were performed in vitro using a 3T3 cell line. Rats underwent either PP (n = 3) or SRT-PP (n = 6) bridge mesh implantation in an anterior abdominal wall defect model. Repair was assessed clinically and radiographically, with integration evaluated by histology and mechanical testing at 60 days.

Results:

Cell proliferation was enhanced on SRT-PP mesh. This was corroborated in vivo by abdominal wall histology, dramatically diminished craniocaudal mesh contraction, improved strength testing, and higher tissue failure strain. There was no increase in seroma or visceral adhesion formation. No foreign body reactions were noted on liver histology.

Conclusions:

SRT applied as a coating appears to augment mesh–tissue integration and improve abdominal wall stability following bridged repair. Further studies in larger animals will determine its applicability for hernia repair in patients.
Pyoderma Gangrenosum–like Wounds in Leukocyte Adhesion Deficiency: Case Report and Review of Literature
Authors: Simpson Andrew M. , Chen Karin , Bohnsack John F. , Lamont Matthew N. , Siddiqi Faizi A. , Gociman Barbu
Published: August 2018

Leukocyte adhesion deficiency (LAD) is a rare primary immunodeficiency characterized by impairment of leukocyte migration during an inflammatory response. LAD patients can experience recurrent neutrophilic wounds similar to pyoderma gangrenosum (PG), predominantly of the skin and mucosal surfaces. There have been only a few reports addressing the management of extensive, life-threatening wounds in LAD patients. We describe here both the systemic and local management employed to successfully treat a severe PG-like cutaneous lesion in the setting of LAD in a 9-year-old female. A comprehensive literature review was performed to identify previously reported similar cases. Under aggressive systemic and local management, the wound was stabilized and complete epithelialization was achieved in 8 months. Eight studies documenting 11 patients with LAD and PG-like lesions were identified in our review of the literature. The complexity of wounds associated with LAD requires an aggressive, multidisciplinary approach. Involvement of pediatrics, immunology, plastic surgery, infectious disease, and physical therapy is essential to obtaining a positive outcome. In the setting of LAD with PG-like lesions, the only viable option is allowing for closure by secondary epithelialization. This was achieved in our patient once the wound was stabilized with the systemic administration of infliximab and topical administration of tacrolimus.
Fingertip Necrosis due to Intravascular Use of Mephedrone: A Case Report
Authors: Francés Mónica , Fuertes Víctor , Casarrubios José M. , Navarro Carlos , Sánchez Olivia C. , Poza Estefania , Fernández-Palacios Javier
Published: August 2018

Mephedrone is a new synthetic cathinone-derived drug. It is a sympathomimetic drug, and its structure is similar to amphetamines, although its specific pharmacokinetics and metabolism remain unknown. We performed a literature search in PUBMED with the following key words: Mephedrone AND Necrosis AND Hand. No results were found. We performed a second literature search with the following key words: Mephedrone AND Physiopathology AND Side effects, obtaining a total of 7 articles that we read before writing this case report. We will present a case report of a 28-year-old man with distal ischemia in his left hand associated to intra-arterial drug use of mephedrone. The patient ended up having superficial necrosis involving skin and subcutaneous tissue in his thumb, which was treated with wound care. Good quality healing, full range of motion, and normal sensitivity were achieved. There are no previous publications related to any side effects secondary to its intravascular use. The ultimate mechanism producing this distal fingertip necrosis remains undefined.
SURGICAL MANAGEMENT OF FULL-THICKNESS MACULAR HOLE SUPERIMPOSED ON EXUDATIVE AGE-RELATED MACULAR DEGENERATION
Authors: Shif Olga A. , Katz Matthew S. J.
Published: August 2018

Background/Purpose:

We describe a case of full-thickness macular hole formation in a patient with exudative age-related macular degeneration after an intravitreal ranibizumab injection and its surgical management.

Methods:

This case is a retrospective, interventional case report.

Results:

A 77-year-old woman with bilateral exudative age-related macular degeneration and pre-existing retinal pigment epithelium tear developed a full-thickness macular hole after intravitreal ranibizumab. The macular hole was repaired successfully with pars plana vitrectomy, internal limiting membrane peel, and 16% C3F8 gas fill.

Conclusion:

To the best of our knowledge, this is the first reported case of full-thickness macular hole after a retinal pigment epithelium tear repaired successfully with vitrectomy, resulting in improved visual acuity.
Corneal Sensitivity After Ocular Surgery
Authors: Lum Edward , Corbett Melanie C. , Murphy Paul J.
Published: August 2018

The cornea is densely innervated with free nerve endings to provide a high level of sensitivity to foreign bodies or noxious substances. They also provide trophic support to the tissues of the cornea and facilitate their repair and replacement. Any reduction in the function of the nerve endings through disease, contact lens wear, or surgery may lead to corneal disease, damage, or reduced healing. Assessment of the corneal nerve function can be made by the use of specialized instruments (aesthesiometers) that stimulate the corneal nerves using different modalities—mechanical, chemical, and thermal. Each modality assesses the function of a different cohort of corneal nerve type. Ocular surgery, particularly corneal surgery, can produce significant damage to the corneal innervation. However, for the majority of surgical procedures, corneal sensation eventually returns to preoperative levels, given enough time. The principal exceptions to this are penetrating keratoplasty, epikeratophakia, and cryo-keratomileusis, where sensation rarely returns to normal. For all types of surgery, the pattern of corneal sensation loss and recovery depends on the type, depth, and extent of incision because these influence the number of nerve fibers severed, and on the healing response of the patient.
Research ethics dilemmas in thyroid disease
Authors: Rosenthal M. Sara , Angelos Peter , Schweppe Rebecca E.
Published: August 2018

Purpose of review

Since research ethics dilemmas frequently fall outside the purview of the Institutional Review Board (IRB), we present three unique recent research ethics cases in thyroidology that demonstrate research ethics dilemmas.

Recent findings

The cases presented raise questions surrounding epistemic/scientific integrity, publication ethics, and professional, and personal integrity.

Research ethics dilemmas that fall outside the purview of the IRB are appropriate for a Research Ethics Consultation, a common service in many large academic medical centers.
Parent‐child Agreement on Health‐Related Quality of Life in Children With Functional Constipation in Primary Care
Authors: van Summeren Jojanneke J.G.T. , Klunder Jan Willem , Holtman Gea A. , Kollen Boudewijn J. , Berger Marjolein Y. , Dekker Janny H.
Published: August 2018

Objective:

Functional constipation (FC) has a major impact on the health‐related quality of life (HRQoL) of children. The aim of this study was to evaluate parent‐child agreement on HRQoL in children (8–17 years) with FC in primary care.

Methods:

Children diagnosed with FC by their clinician were eligible. HRQoL was measured with the Defecation Disorder List (DDL, score 0–100), and the EuroQol‐5‐Dimension‐Youth Visual Analogue Scale (EQ‐5D‐Y‐VAS, scale 0–100). Parent‐child agreement was examined with discrepancy scores, intraclass correlation coefficients and Bland‐Altman plots.

Results:

Fifty‐six children, median age of 10 years (IQR 8–12) and their parents were included. Parent‐child agreement at a group level was good, with an intraclass correlation coefficient of 0.80 (95% confidence interval 0.67 to 0.88) for the DDL, and 0.78 (95% confidence interval 0.65 to 0.87) for the EQ‐5D‐Y‐VAS. Mean discrepancy scores for the DDL and EQ‐5D‐Y‐VAS were small: −2.6 and −2.9, implying that parents were slightly more positive about the HRQoL than their children. Bland‐Altman plots showed considerable discordance between individual parent‐child pairs. Limits of agreement were −19.7 and 14.6 for the DDL and −27.6 and 21.8 for the EQ‐5D‐Y‐VAS.

Conclusions:

There is good parent‐child agreement on HRQoL in children with FC at group level. However, a substantial number of parent‐child pairs differed considerably on their rating of the HRQoL of the child. Therefore, we recommend clinicians, if they want to have an impression of the impact of the FC on the HRQoL of the child, to ask both the child and the parent(s).
A Case of Allergic Broncopulmonary Aspergillosis Associated With Hematopoietic Stem Cell Transplantation Due to Chronic Granulomatous Disease
Authors: Malbora Baris , Aksoylar Serap , Ozdemir Hamiyet H. , Ozdemir Sinem , Kansoy Savas
Published: August 2018

Allergic bronchopulmonary aspergillosis is an immunologic pulmonary disorder caused by hypersensitivity to Aspergillus fumigatus. This disorder is most commonly seen in patients with poorly controlled asthma and cystic fibrosis. It is rarely reported in chronic granulomatous disease patients; however, there are no cases reported with hematopoietic stem cell transplantation in the English literature. Herein, we report a patient with chronic granulomatous disease who had hematopoietic stem cell transplantation and subsequently developed allergic bronchopulmonary aspergillosis.
Lepidic, Papillary Components and EGFR Mutations are Frequent in Patients With Lung Adenocarcinoma Who are Over 75 Years Old
Authors: Forest Fabien , Patoir Arnaud , Dal-Col Pierre , Da Cruz Vanessa , Camy Florian , Stachowicz Marie-Laure , Bayle-Bleuez Sophie , Fournel Pierre , Karpathiou Georgia , Péoc’h Michel
Published: August 2018

Treatment for lung adenocarcinoma frequently diverges from standard treatment in older patients. Clinical, pathologic, and molecular characteristics of lung cancer in patients over 75 years old have not been fully described. The aim of our work was to describe the rate of EGFR, KRAS, BRAF

V600
, and HER2 mutations, and ALK rearrangement and pathologic characteristics in patients with lung adenocarcinoma over 75, compared with patients below 75 years old. This is a retrospective study from 2 cohorts: a histopathologic cohort of all consecutively resected lung adenocarcinoma in our institution for patients over 75 (n=54, from 2006 to 2017) compared with patients below 75 years old (n=148, from 2014 to 2017) and a molecular cohort of all stage IIIb or IV lung adenocarcinoma from 2009 to 2017 (n=1611). Papillary and lepidic components were more frequently found in patients over 75 years old (P=0.046 and 0.0078, respectively). The rate of current smokers was lower in older patients (P<0.0001). EGFR mutations were more frequent in patients over 75 than in younger patients: 17% versus 8.1% (P<0.0001). The mutually exclusive KRAS mutation was more frequent in patients below 75 years old than in older patients: 25.8% versus 12.8% (P<0.0001). There was no difference for the proportion of the 2 most frequent EGFR mutations (exon 19 deletion and L858R mutation) (P=0.85) or KRAS-mutated codon (P=0.22) between tumors in younger or older patients. There was no statistically significant difference for the presence of BRAF

V600
, HER2 mutations, and ALK rearrangement (P=0.44, 0.71, and 1, respectively). Our work highlights the fact that EGFR mutations are more frequent in patients over 75 years old in our population. We can hypothesize that this difference might be mainly caused by the less frequent occurrence of tobacco-smoking–related lung cancers in the elderly and the presence of a lepidic or papillary component in this age group.
Immunohistochemistry in the Detection of Early Myocardial Infarction: Systematic Review and Analysis of Limitations Because of Autolysis and Putrefaction
Authors: Barranco Rosario , Ventura Francesco
Published: August 2018

The postmortem diagnosis of acute myocardial infarction is one of the main problems in forensic practice, especially in cases in which death occurs soon after (from minutes to a few hours) the onset of the ischemic damage. Several authors have highlighted the possibility to overcome the limits of conventional histology in this diagnosis by utilizing immunohistochemistry. In the present research, we examined over 30 scientific studies and picked out over 20 main immunohistochemical antigens analyzed with a view to enabling the rapid diagnosis of early myocardial infarction. The aim of our review was to examine and summarize all the principal markers studied to date and also to consider their limitations, including protein alteration because of cadaveric autolysis and putrefaction.
Beneficial Effect of Heat-induced Antigen Retrieval in Immunocytochemical Detection of Intracellular Antigens in Alcohol-fixed Cell Samples
Authors: Cizkova Katerina , Flodrova Pavla , Baranova Romana , Malohlava Jakub , Lacey Matthew , Tauber Zdenek
Published: August 2018

Immunohistochemistry and immunocytochemistry (ICC) play an irreplaceable role in research and diagnostics. It is well known that antigen retrieval (AR) can, as a technique, have beneficial outcomes on immunohistochemistry results when using formalin-fixed, paraffin-embedded tissue samples. The main purpose of AR is to break protein crosslinks which are formed during formalin fixation. Although AR was originally designed for formalin-fixed, paraffin-embedded samples, the usefulness of AR in ICC has been described in previous studies. Cytologic samples are often fixed in alcohol-based fixatives which does not lead to the formation of crosslinks. Therefore, alcohol-fixed samples can be successfully immunostained without AR. We investigated the effect of heat-induced antigen retrieval (HIAR) on alcohol-fixed HEK293 cell line samples and patient cytologic samples from thyroid gland obtained by fine needle aspiration technique. We compared indirect 2-step ICC staining results performed according to the protocol with or without HIAR in citrate buffer pH 6 for several antibodies. Utilizing HIAR against intracellular antigens has beneficial effects. Therefore, more diluted antibodies can be used for satisfactory results. However, surface antigens were probably damaged by HIAR treatment. We demonstrated evident changes in cell surface topography after HIAR treatment by atomic force microscopy. Staining specificity of patient samples improves and background staining is reduced, allowing higher dilutions of primary antibody. Improving staining specificity is necessary for accurate diagnostics. Although we have shown the beneficial effect of HIAR for immunostaining intracellular antigens, proper staining protocol should be tested on appropriate controls for individual antibodies.
Correlating Changes in the Epithelial Gland Tissue With Advancing Colorectal Cancer Histologic Grade, Using IHC Stained for AIB1 Expression Biopsy Material
Authors: Theodosi Angeliki , Glotsos Dimitris , Kostopoulos Spiros , Kalatzis Ioannis , Tzelepi Vassiliki , Ravazoula Panagiota , Asvestas Pantelis , Cavouras Dionisis , Sakellaropoulos George
Published: August 2018

Objective:

The objective of this study was to study the textural and color changes occurring in the epithelial gland tissue with advancing colorectal cancer (CRC), utilizing immunohistochemical stain for AIB1 expression biopsy material.

Material and Methods:

Clinical material comprised biopsy specimens of 67 patients with a diagnosis of CRC. Two experienced pathologists used H&E-stained material for grading CRC lesions and immunohistochemical (IHC) stain for AIB1 expression. Twenty six patients were diagnosed with grade I, 28 with grade II, and 13 with grade III CRC. Guided by pathologists, we selected the regions of interest from AIB1-digitized images of each patient, encompassing the epithelial gland, and we computed 69 features, quantifying textural and color properties of the AIB1-stained lesions. We evaluated the statistical differences between grades by means of the Wilcoxon statistical test for each feature, and we assessed changes in feature values with advancing tumor grade by means of the Point Biserial Correlation.

Results:

Statistical analysis revealed 14 single features, quantifying textural and color properties of the epithelial gland, which sustained statistically significant differences between LG-CRC and HG-CRC cases. These features were drawn from the gray-level image histogram, the cooccurrence matrix, the run length matrix, the discrete wavelet transform, the Tamura method, and the L*a*b color transform.

Conclusions:

A systematic statistical analysis of AIB1-stained biopsy material showed that high-grade CRC lesions contain higher intensity levels, appear coarser, are more homogeneous with smooth variation across the image, have lower contrast that is slowly varying across the image, have lower AIB1 staining, and have lower edges. A combination of textural and color attributes, evaluating image gray-tone distribution, textural roughness, inhomogeneity, AIB1 staining, and image coarseness should be considered in evaluating AIB1-stained CRC lesions.
LI-cadherin and CDX2: Useful Markers in Metastatic Gastrointestinal Adenocarcinoma Cells in Serous Cavity Effusion
Authors: Ma Haifen , Yu Jihong , Tang Jingjing
Published: August 2018

Objective:

The aim of this study was to investigate the expression and significance of liver-intestine cadherin (LI-cadherin) and CDX2 (caudal-type homeobox transcription factor 2) in cytology specimens of metastatic gastrointestinal adenocarcinoma in serous cavity effusion.

Materials and Methods:

The serous cavity effusion samples that were suspected of tumor metastasis in the last 5 years were made into paraffin-imbedded cell blocks, a total of 180 cases, including 97 cases of pleural effusion, 78 cases of ascites, and 5 cases of pericardial effusion. The expressions of LI-cadherin and CDX2 were detected by immunohistochemical staining in cell blocks and primary tumor tissues; thereafter, the specificity and sensitivity were analyzed.

Results:

The positive expressions of LI-cadherin and CDX2 in 63 cases of gastrointestinal adenocarcinoma cells were 65.1% (41/63), 61.9% (39/63), respectively. Of 11 cases of pancreaticobiliary duct cancers, only one case (9.09%) was weakly positive for LI-cadherin and CDX2 expressions, and 107 cases of non–digestive tract cancers were all negative. In 57 matched-pair samples of cell blocks and primary gastrointestinal adenocarcinoma tissues, the positive expressions of LI-cadherin and CDX2 were 64.9% (37/57), 61.4% (35/57), respectively, in cells, and 82.5% (47/57), and 77.2% (44/57), respectively, in tissues. Positive correlation was observed between the expressions of LI-cadherin and CDX2 in metastatic gastrointestinal adenocarcinoma cells (P<0.05). Both LI-cadherin and CDX2 expressions demonstrated positive correlation in cells with paired cancer tissues (P<0.05). The positive expression reached 80.7% with at least one positive marker in the total cell samples through combined detection of LI-cadherin and CDX2, increased by 15.8% and 19.3% compared with using either of the markers alone.

Conclusions:

Combined use of LI-cadherin and CDX2 can improve the accuracy in the diagnosis of metastatic adenocarcinoma cells in serous cavity effusion and provide some bases of histologic origin because of their high sensitivity and specificity.
Interleukin-1 Receptor Antagonist Is Associated With Pediatric Acute Respiratory Distress Syndrome and Worse Outcomes in Children With Acute Respiratory Failure*
Authors: Dahmer Mary K. , Quasney Michael W. , Sapru Anil , Gildengorin Ginny , Curley Martha A. Q. , Matthay Michael A. , Flori Heidi
Published: August 2018

Objectives:

To test whether plasma interleukin-1 receptor antagonist or variants within the gene encoding for interleukin-1ra (IL1RN), or proteins involved in regulating interleukin-1β levels or interleukin-1β response, are associated with pediatric acute respiratory distress syndrome or outcomes in mechanically ventilated children with parenchymal lung disease.

Design:

Prospective cohort study.

Setting:

Twenty-two PICUs participating in the multisite clinical trial, Randomized Evaluation of Sedation Titration for Respiratory Failure (U01 HL086622).

Subjects:

Children 2 weeks to 17 years old treated with invasive mechanical ventilation for acute airways and/or parenchymal lung disease.

Measurements and Main Results:

Three-hundred seventy-eight of 549 patients had pediatric acute respiratory distress syndrome; DNA and plasma were obtained from 523 of 549 and 480 of 549 patients, respectively. Plasma interleukin-1ra was highest on the day of intubation (day 0) and decreased over the subsequent 3 days (p < 0.0001). Interleukin-1ra level was higher in patients with pediatric acute respiratory distress syndrome than those without pediatric acute respiratory distress syndrome (p < 0.0001). Multivariable regression analysis of data across all days demonstrated a significant association of interleukin-1ra (odds ratio, 1.30; 95% CI, 1.10–1.52; p = 0.002) and day (p < 0.05) with pediatric acute respiratory distress syndrome, independent of age and Pediatric Risk of Mortality-III score. Analysis on individual days indicated that plasma interleukin-1ra levels were associated with pediatric acute respiratory distress syndrome on days 0 and 2, independent of age and Pediatric Risk of Mortality-III score (p = 0.04 and 0.003, respectively), however did not quite reach significance on days 1 and 3 (p = 0.06 and 0.07, respectively). Interleukin-1ra was independently associated with mortality on day 1 (p = 0.02). Interleukin-1ra also correlated with length of mechanical ventilation, measures of oxygenation, and PICU length of stay. No genetic variants were associated with pediatric acute respiratory distress syndrome.

Conclusions:

Plasma interleukin-1ra is associated with pediatric acute respiratory distress syndrome, PICU length of stay, length of mechanical ventilation, and mortality in children with acute respiratory failure requiring mechanical ventilation.
Belly Dancer Syndrome
Authors: Ossella Chiara , Dell'Omo Floriana , Zanetti Elena , Pestalozza Isabella Ferdinanda , Galizia Pierluigi , Tripodi Salvatore
Published: August 2018

Background

Belly dancer syndrome is a rare condition consisting of involuntary, repetitive, often rhythmic contractions of the diaphragm, causing undulating movements of the abdomen that recall those of a belly dancer. It is frequently associated with pain or discomfort in the upper abdomen or lower chest, but clinical symptoms are highly variable often resulting in late diagnosis. Very few pediatric cases have been reported, all of which were secondary to other conditions, and to our knowledge, no idiopathic cases of Belly Dancer Syndrome have been reported in children.

Case

We present the case of a 14-year-old girl who presented to the emergency department with sudden onset of abdominal pain. She was initially diagnosed and treated for pancreatitis because blood tests revealed very high lipase, but when jerky abdominal wall movements became pronounced, belly dancer syndrome was suspected. Full work-up included abdominal ultrasound, chest x-ray, electroencephalogram, electromyography, magnetic resonance imaging, and toxic screen, all of which were normal. She was treated successfully with oral diazepam and referred to a pediatric neuropsychiatrist.

Conclusions

Belly dancer syndrome is a rare condition often misdiagnosed owing to multiple presentations. Increased awareness is necessary to prevent late diagnosis and incorrect treatment.
Individual and Environmental Determinants of Late-Life Community Disability for Persons Aging With Cardiovascular Disease
Authors: Keeney Tamra , Jette Alan M.
Published: August 2018

Objective

The aim of the study was to estimate the prevalence of late-life community disability for adults 65 yrs and older with cardiovascular disease versus those without. This study also investigated the contributions of environmental and individual risk factors on late-life community disability for persons with cardiovascular disease.

Design

This is a secondary data analysis of the 2016 round of the National Health and Aging Trends Study. The study sample included community-dwelling Americans with cardiovascular disease (n = 1490) and without (n = 4819). Logistic regression was used to estimate associations between individual risk factors, environmental factors, and community disability for those with cardiovascular disease.

Results

Individuals with cardiovascular disease had a significantly higher prevalence of late-life community disability than those without (44.8% vs. 29.0%). For persons with cardiovascular disease, lack of transportation, home modification, and needing assistance with mobility increased the odds of community disability. Younger age and lower comorbidity were associated with decreased odds of community disability. When accounting for environmental factors in multivariate analyses, sex, race, and education were not significantly associated with community disability.

Conclusion

Late-life community disability is highly prevalent for persons aging with cardiovascular disease. Intervention strategies to deter late-life community disablement should focus on improving access to transportation and improving the community environment in which older adults live.
Protein Kinase C-Delta (PKCδ) Tyrosine Phosphorylation is a Critical Regulator of Neutrophil-Endothelial Cell Interaction in Inflammation
Authors: Soroush Fariborz , Tang Yuan , Guglielmo Kimberly , Engelmann Alex , Liverani Elisabetta , Patel Akruti , Langston Jordan , Sun Shuang , Kunapuli Satya , Kiani Mohammad F. , Kilpatrick Laurie E.
Published: August 2018

Background:

Neutrophil dysfunction plays an important role in inflammation-induced tissue injury. Previously, we identified protein kinase C-δ (PKCδ) as a critical controller of neutrophil activation and trafficking but how PKCδ is regulated in inflammation has not been delineated. PKCδ activity is regulated by tyrosine phosphorylation on multiple sites. Tyrosine155 is a key regulator of apoptosis and gene expression, but its role in proinflammatory signaling is not known.

Methods:

In-vitro studies – superoxide anion (O2
−) and neutrophil extracellular traps (NETs) were measured in bone marrow neutrophils (BMN) isolated from wild type (WT) and PKCδY155F knock-in mice (PKCδ tyrosine 155 → phenylalanine). Our novel 3D biomimetic microfluidic assay (bMFA) was used to delineate PKCδ-mediated regulation of individual steps in neutrophil adhesion and migration using WT and PKCδY155F BMN and mouse lung microvascular endothelial cells (MLMVEC). In-vivo studies – WT and PKCδY155F knock-in mice underwent sham or cecal ligation and puncture surgery and the lungs harvested 24 h post-surgery.

Results:

In vitro – PKCδY155F BMN had significantly reduced O2
− and NETs release compared with WT. WT BMN, but not PKCδY155F BMN, demonstrated significant adhesion and migration across tumor necrosis factor-activated MLMVEC in bMFA. PKCδ inhibition significantly reduced WT BMN adhesion and migration under low shear and near bifurcations, but had no effect on PKCδY155F BMN. In vivo – mutation of PKCδ tyrosine 155 significantly decreased neutrophil migration into the lungs of septic mice.

Conclusions:

PKCδ tyrosine 155 is a key phosphorylation site controlling proinflammatory signaling and neutrophil–endothelial cell interactions. These studies provide mechanistic insights into PKCδ regulation during inflammation.