bluuebunny/crossref_metadata_2025 huggingface dataset:
PB2411 DETECTION OF PATERNALLY INHERITED MUTATION (IVS‐II‐I G → A) OF THALASSEMIA IN MATERNAL PLASMA BY USING DHPLC METHODS
Authors: Zafari M.
Published: June 2019

Background:

β‐ Thalassemia is the most common inheritable disease in the world. About 3% of populations (150 million persons) are β‐thalassemi carriers’, and they run 25% risk of having Thalassemia major baby in each pregnancy. Prenatal diagnosis (PND) if offered in many country for prevent Thalassemia, and it is a part of national prevention program by invasive methods, such as; chorionic villus sampling (CVS) at 11‐14 weeks gestation or amniocentesis (AC) from 15 weeks gestation.

Aims:

the purpose of this study was detection of paternally inherited mutation (IVS‐II‐I G → A) of Thalassemia in maternal plasma by using DHPLC methods with its assessments via sensitivity and specificity determinations for prenatal diagnosis of thalassemia major.

Methods:

Subjects included Iranian pregnant women who at risk of having fetuses with β‐thalassemia major. We focused exclusively on samples in which the father was carrier for IVS II‐I G → A mutation and the mother had been genotyped to carry another β‐globin gene mutation. 10 ml peripheral blood sample were obtained from 50 pregnant women. The CVS sample was obtained Trans abdominal puncture with a 23‐gauge needle under ultrasound guidance. The samples were analyzed by reveres dot blot analysis. We were masked as to the identity the samples with numerical coding system, so, these were examined in a blinded manner. Circulatory DNA was extracted from 200 μl of peripheral blood plasma with QIAamp DNA mini and blood kit (QIAGEN‐USA) according to the manufacture s instructions. The genomic DNA concentration was measured by NanoDrpe system (ND1000, USA) and electrophoresis. They stored at ‐20 c until used. At firs beta‐Globin gene fragments containing IVSII‐1(G > A) mutation was amplified with HRM real time PCR, also by using specific primers. DHPLC was performed on the WAVW fragment analysis system (Transgenomic Inc, USA) to detect the variants of beta globins’ gene mutation of Thalassemia. In order to generate the hetro& homoduplexes, we mixed an equal amount of HRM Real time PCR product of wild type and patients.

Results:

the sensivity, specifity of this method was 40. 62 and 61.12; also the PPV and NPV was 65% and 36.67% respectively.

Summary/Conclusion:

the specifity and NPV of DHPLC method is higher than specifity and PPV.
PB2415 HYDROXYUREA AN EFFECTIVE THERAPY TO AVOID SPLENECTOMY IN SICKLE CELL DISEASE AND THALASSEMIA: 15 YEARS EXPERIENCE IN SAUDI ARABIA
Authors: Jaouni S. Al
Published: June 2019

Background:

Background and Purpose: Spleen plays an important part in the immune system which helps the body fight infection and have a major role in children. Splenectomy have been decline in hemoglobin disorders in recent years.

Aims:

To assess the role of hydroxyurea if can eliminate the risk of splenectomy in sickle cell disease (SCD) and thalassemia in our medical center.

Methods:

Total of 84 patients enrolled in the study between 2003 to 2018 at King Abdulaziz University Hospital, Faculty of Medicine, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia, 24 sickle cell disease (SCD), 28 thalassemia major (TM) were suboptimal transfusion dependents and hypersplenism, 22 thalassemia inter media (TI).

Results:

Risk of splenectomy have been avoided in 23/24 SCD, 27/28 in TM and 22/22 in TI.

Summary/Conclusion:

Hydroxyurea is an effective and safe therapy can eliminate risk of splenectomy in SCD and thalassemia. Recent studies and meta analysis showed that hydroxyurea is safe and non‐carcinogenic.
PB2419 PEPTIDE CORRECTION OF OSMOTIC RESISTANCE DISORDERS IN INFLAMMATION
Authors: Golubeva M. , Umarova B. , Bondarenko N.
Published: June 2019

Background:

The development of inflammation is accompanied by a change in the rheology of the blood ‐ an increase in viscosity, aggregation, a decrease in the osmotic resistance of red blood cells, which indicates a change in the structure of their membrane. This leads to a change in the functional properties of red blood cells and impaired microcirculation. The search for new anti‐inflammatory drugs, devoid of side effects is relevant. Promising may be endogenous regulatory peptides of the glyproline family, which have a prophylactic and therapeutic effect in various pathological conditions.

Aims:

The aim of this study was to investigate changes in the osmotic resistance of erythrocytes in the dynamics of experimental peritonitis with the introduction of the peptide Pro‐Gly‐Pro (PGP).

Methods:

A pro‐inflammatory agent was used to simulate experimental peritonitis ‐ 40% sodium thioglyaolate solution 4 g/kg, administered intraperitoneally. The erythrocyte osmotic resistance (ORE) was determined 30 minutes, 2 and 18 hours after the induction of inflammation. The evaluation of the wholesale electricity market was carried out to determine the degree of hemolysis in hypotonic solutions of sodium chloride. The light transmittance was recorded on a photoelectrocalorimeter at a wavelength of 580 nm. All experiments were performed in accordance with the ethical principles and regulatory documents recommended by the ESF and the declaration of a humane attitude towards animals.

Results:

The development of inflammation is accompanied by a decrease in the osmotic resistance of erythrocytes. Statistically significant differences in the wholesale electricity market from control were observed 2 hours after the administration of the thioglycolate. The introduction of PGP peptide at a dose of 3.7 μm/kg before the induction of inflammation reduced pathological changes in the ORE. The percentage of hemolyzed cells decreased, the differences were significant in solutions with salt content of 0.4% and 0.3%. The peptide, introduced against the background of developed inflammation (1 hour and 45 minutes after the introduction of thioglycolate) did not have a corrective effect on the ORE.

Summary/Conclusion:

The results indicate the ability of PGP to exert a preventive protective effect on the erythrocyte membrane, preventing a decrease in the ORE.
PB2430 CHANGES OF TPA AND PAI‐1 IN PATIENTS WITH CORONARY ARTERY DISEASE.
Authors: Tyravska Y. , Lizogub V. , Vovk T. , Savchuk O.
Published: June 2019

Background:

Impaired fibrinolysis, with imbalance between the key enzyme of plasminogen to plasmin activation, tissue plasminogen activator (tPA), and its main endogenous inhibitor, plasminogen activator inhibitor‐1 (PAI‐1), is shown to play a crucial role in thrombi formation which is an essential process in acute coronary syndrome (ACS). Most studies exist regarding myocardial infarction (MI). Limited investigations include patients with unstable angina (UA). However, no data is found concerning types of UA, namely, new‐onset angina (NUA) and progressive angina (PUA). Consequently, we investigated concentrations of tPA, PAI‐1 and tPA/PAI‐1 ratio in patients with above‐mentioned types of coronary artery disease (CAD).

Aims:

to compare the concentration of tPA and PAI‐1, tPA/PAI‐1 ratio in patients with different types of CAD (including NUA and PUA).

Methods:

In this cross‐sectional study, we collected blood samples in 94 patients with CAD ‐ 10 patients with MI, 57 patients with UA (38 patients with PUA and 19 patients with NUA), 27 patients with chronic coronary disease (stable angina (SA)). Concentrations of tPA and PAI‐1 were determined by standart method ELISA. Ratio tPA/PAI‐1 was calculated. There were no significant difference between groups of patients with respect of age, gender and body mass index.

Results:

In our study, we observed significant difference in tPA concentration (p = 0,0001) and tPA/PAI‐1 ratio (p = 0,004). However, PAI‐1 did not differ significantly in groups (p = 0,326), though it tended to be higher in patients with ACS in comparison with SA (0,392 (0,324‐0,472) U/ml vs 0,321 (0,284‐0,456) U/ml, p = 0,100). Unexpectedly, we identified the highest PAI‐1 concentration in UA group.

Both tPA and tPA/PAI‐1 were significantly lower in ACS in contrast to SA (0,226 (0,173‐0,233) U/ml and 0,514 (0,432‐0,625) vs 0,234 (0,222‐0,295) U/ml and 0,619 (0,505‐0,997), p = 0,016 and p = 0,039, respectively).

We detected significantly lower tPA concentration and tPA/PAI‐1 in patients with UA in comparison with SA (0,219 (0,173‐0,230) U/ml vs 0,234 (0,222‐0,256) U/ml, p = 0,002, and 0,485 (0,427‐0,597) vs 0,619 (0,505‐0,811), p = 0,021, respectively).

Finally, we revealed significant difference in tPA concentration and tPA/PAI‐1 between NUA and PUA (p = 0,0001 and p = 0,001, respectively). Moreover, there were no difference between tPA concentration and tPA/PAI‐1 in MI and NUA (p = 0,071 and p = 0,756, respectively) as well as SA and PUA (p = 0,153 and p = 0,188, respectively). Additionally, the lowest tPA/PAI‐1 ratio was in NUA group.

Summary/Conclusion:

We have established imbalance between concentrations of tPA and PAI‐1 depending on CAD type. Thus, the highest thrombotic activity was detected in UA group while the lowest fibrinolytic activity was in NUA group. These findings call for further studies within types of UA as well as MI.

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PB2440 CHARACTERISTICS OF PATIENTS WITH CANCER TREATED FOR VENOUS THROMBOEMBOLISM IN GENERAL HOSPITAL DR. JOSIP BENČEVIĆ DURING FIVE YEARS
Authors: Holik H. , Coha B. , Peić A. Kovač , Pulanić D.
Published: June 2019

Background:

In the Republic of Croatia cancer is the second cause of mortality after cardiovascular disease. Patients with cancer have a 4 to 7‐fold higher risk of developing venous thromboembolism (VTE) and those who developed VTE have poorer survival than those without VTE. The greatest risk of developing VTE is present in pancreatic, brain, stomach and ovarian cancer, while the lowest risk is with breast and prostate cancer.

Aims:

Analyze characteristics of patients with cancer who were treated for VTE in General Hospital Dr. Josip Benčević for a period of five years.

Methods:

In the General Hospital Dr Josip Benčević ‐ location of Slavonski Brod longitudinal observational analyzes of patients with cancer and newly diagnosed VTE treated in hospital during 2011‐2015.

Results:

A total of 546 cases of VTE were diagnosed in the period of 5 years, out of which 134 (25%) patients with cancer. In patients with cancer and VTE (134) 46% were female while the median age was 67 years, ranging from 38 to 89 years. 87 (65%) patients had deep vein thrombosis (DVT), pulmonary embolism (PE) had a 34 (25%) while 13 (10%) patients had PE and DVT simultaneously. Cancer was only risk factor for development of VTE in 44 (33%) patients, while others had one or more additional risk factors; 51 patients (38%) were treated with possible thrombogenic chemotherapy, 36 (27%) had surgery within 6 months of diagnosis, 15 (11%) patients had sepsis and 18 (13%) were immobilized. A total of 27 (20%) patients died, 16 out of pulmonary embolism, 10 from cancer and 1 from sepsis as a main cause of death. The most common primary cancer sites were: lung 17%, colon and rectum 16%, haematological malignancies 11%, pancreas 9%, ovary 8%, prostate 7%, breast 6%, liver and gallbladder 6%, urinary bladder 5 % and stomach 4%.

Summary/Conclusion:

The results of our analysis are consistent with data from the literature on VTE incidence and the percentage of VTE caused by cancer. Distrubution of patients with cancer and VTE according to primary cancer site is also like data from literature – most cases were with lung and colon cancer who are the most common cases of cancer in our population while the most thrombogenic cancer in our study was pancreas. VTE prevention in patients with high risk of developing VTE is a priority in today's treatment. Strong adherence of the appropriate thromboprophylaxis is required to reduce the incidence of VTE in the cancer patients.
PB2441 DIRECT ORAL ANTICOAGULATION IN PATIENTS WITH MYELOPROLIFERATIVE NEOPLASMS: A SINGLE‐CENTER REAL‐LIFE EXPERIENCE
Authors: Raso S. , santoro M. , Napolitano M. , Mancuso S. , Accurso V. , Carlisi M. , Tarantino G. , Siragusa S.
Published: June 2019

Background:

The risk of developing a venous thromboembolic event (VTE) in Myeloproliferative Neoplasms (MPNs) accounts from 5 to 10‐fold the general population risk. According to recommendations of European Leukemia Net, patients affected by MPNs already diagnosed with VTE have to be considered at high risk for VTE recurrence. To date the standard treatment adopted for prevention and treatment of VTE in this setting of patients is represented by low molecular weight heparin (LMWH) and vitamin K antagonists (AVK). Recent data have demonstrated the noninferiority of direct oral anticoagulant (DOAC) drugs, when compared to LMWH, in preventing VTE recurrences in patients affected by cancer with an acceptable toxic profile. However, there are only scarce evidences on the safety and efficacy of DOACs in patients with hematological malignancies.

Aims:

Our aim is to collect real‐life data on the use, efficacy and safety of DOACs in patients with diagnosis of MPNs.

Methods:

Data from 51 patients affected by MPNs on anticoagulant therapies were collected. Of them, 27 were on treatment with AVK, 4 on LMWH and 20 on DOAC. Data from the 20 MPNs patients taking DOACs for treatment/prevention of VTE or atrial fibrillation (AF) were retrospectively collected in a specific database. Data were analyzed with descriptive statistic tools. Adverse events were graded according to the “Common Terminology Criteria – Adverse Events” (CTC‐AE) scale.

Results:

14/20 (70%) of the patients on treatment with DOAC have the indication for prevention of VTE recurrences and 6/20 (30%) for AF. Of the 20 patients, 5 were taking dabigatran, 6 rivaroxaban, 3 apixaban and 4 edoxaban. Of the 14 patients on anticoagulation treatment for prevention of VTE, 2 (14.3%) patients failed prevention and showed VTE recurrence: in one case, because of drug failure a second line prophylaxis therapy with warfarin was started; in the second case, failure was due to inadequate cytoreduction for MPN and the DOAC was not dropped. Bleeding was registered in three cases: 2 graded as first and 1 as second grade as per CTC AE classification. Grade 2 bleeding was resolved with dose reduction of anticoagulation treatment. None of the patient was concomitantly under antiplatelet therapy.

Summary/Conclusion:

Real life data from a single center experience on the use of DOAC in patients with MPN suggest that also in these setting of patients DOACs are safe. More extensive data collection is needed to confirm these preliminary findings.
PB2442 BRONCHOSCOPIC TREATMENT WITH FRESH FROZEN PLASMA AND TISSUE PLASMINOGEN ACTIVATOR FOR A CHILD WITH TYPE 1 PLASMINOGEN DEFICIENCY
Authors: Hangul M. , Tuzuner A. B. , Somekh I. , Klein C. , Patıroglu T. , Unal E. , Kose M.
Published: June 2019

Background:

Congenital plasminogen deficiency is a genetic disease with autosomal recessive inheritance pattern. Fibrous plaques that accumulate in the mucosal surfaces of oral cavity, eye and respiratory tract.

Aims:

We aimed to report the first bronchoscopic usage of fresh frozen plasma (FFP) and tissue plasminogen activator (t‐PA) for respiratory complications of a child with plasminogen deficiency.

Methods:

A child with plasminogen deficiency treated with FFP, t‐PA is reported.

Results:

A one‐year‐old male patient was admitted to the hospital for 1 week with cough and increased respiratory distress. Antibiotic therapy was started for bronchopneumonia.

From his medical history it was learned that he had lingous conjunctivitis, in addition a ventriculo‐peritoneal shunt was inserted due to hydrocephalus in the antenatal period. His parents were cousins. The patient had significant paracardiac infiltrations, linear infiltrations in the parenchyma of the chest x ray. The patient was thought to have plasminogen deficiency by clinical findings and his plasminogen level was found to be 14% (N: 70‐130%).

Type 1 plasminogen deficiency and related pulmonary involvement were considered. Bronchoscopy was performed. There were fibrin deposits in the trachea and bronchi. Recurrent pulmonary lavage was performed with FFP and t‐PA. Fibrin plugs occluding the bronchial cuffs were decreased and some of them disappeared.

The patient recovered from respiratory distress that required high flow oxygen therapy, and discharged. Homozygous frameshift mutation in the PLG gene was detected.

Summary/Conclusion:

In this case, it has been firstly reported that total pulmonary lavage treatment with FFP and t‐PA can be a useful treatment method for paitents with plasminogen deficiency in the English literature.
Development of the Diverse Standardized Patient Simulation Cultural Competence Education Strategy
Authors: Ozkara San Eda
Published: June 2019

This article describes the development of the diverse standardized patient simulation (DSPS) cultural competence education strategy, which is designed to improve students’ knowledge, skills, and attitudes with regard to providing culturally competent care. Development of the DSPS was guided by the Jeffreys’ Cultural Competence and Confidence model. As a carefully orchestrated educational intervention utilizing standardized patient pedagogy, the DSPS had content validity review and followed international guidelines and standards for design, implementation, evaluation, and standardized patient training. This strategy was integrated into a nine-credit, 15-week medical-surgical nursing course. A step-by-step description for the development of the DSPS is provided.
Effective Cerebral Perfusion Pressure: Does the Estimation Method Make a Difference?
Authors: Grüne Frank , Mik Egbert G. , Dieters Erik , Hoeks Sanne E. , Stolker Robert Jan , Weyland Andreas , Visser Gerhard H.
Published: June 2019

Introduction:

The effective cerebral perfusion pressure (CPPe), zero-flow pressure (ZFP), and resistance area product (RAP) are important determinants of cerebral blood flow. ZFP and RAP are usually estimated by linear regression analysis of pressure-velocity relationships of the middle cerebral artery. The aim of this study was to validate 4 other estimation methods against the standard linear regression method.

Methods:

In a previous study, electroencephalography, arterial blood pressure, and middle cerebral artery flow velocity were measured in patients during internal cardioverter defibrillator implantation procedures to determine the electroencephalography frequency ranges that represent ischemic changes during periods of circulatory arrest. In this secondary analysis, arterial blood pressure and middle cerebral artery flow velocity were used to estimate CPPe, ZFP, and RAP by 4 different methods—the 3-point intercept calculation (LR3, systolic/mean/diastolic) and methods described by Czosnyka (systolic/diastolic), Belford (mean/diastolic), and Schmidt (systolic/diastolic)—and compare them with the reference linear regression method. CPPe was calculated as the difference between mean arterial pressure and ZFP. The primary endpoint was the difference, correlation, and agreement of these differently estimated CPPe measurements.

Results:

In total, 174 measurements in 35 patients were collected under steady-state conditions before the first circulatory arrest phase during internal cardioverter defibrillator testing. CPPe, ZFP, and RAP measurements based on the 3-point intercept and Czosnyka calculation methods showed small mean differences, good agreement, low percentage errors, and excellent correlation when compared with the reference method. Agreement and correlation were moderate for the Belford method and unsatisfactory for the Schmidt method.

Conclusions:

CPPe, ZFP, and RAP measurements based on 2 alternative calculation methods are comparable to the linear regression reference method.
Cervical Laminectomy With or Without Lateral Mass Instrumentation
Authors: Kim Boaz Sungwhan , Dhillon Rana Singh
Published: June 2019

Study design:

Narrative review.

Background:

Cervical decompressive laminectomy is a common posterior approach for addressing multilevel cervical spondylotic myelopathy. However, there is a concern that cervical laminectomy can lead to kyphotic deformity with subsequent neurological decline. In this context, cervical laminectomy with fusion using lateral mass instrumentation has become increasingly utilized with the aim of reducing the risk of developing postoperative kyphotic deformity, which is thought to predispose to poorer neurological outcomes in the long term.

Objective:

To compare the evidence for stand-alone cervical laminectomy with laminectomy with posterior fusion in terms of clinical outcomes and the incidence of adverse events, particularly the development of postoperative cervical kyphosis.

Material and Methods:

Initial Medline search using MeSH terms yielded 226 articles, 23 of which were selected. An additional PubMed search and the reference list of individual papers were utilized to identify the remaining papers of relevance.

Results:

Cervical laminectomy both with and without fusion offers effective decompression for symptomatic multilevel cervical spondylotic myelopathy. The incidence of postlaminectomy kyphosis is lower following posterior fusion; however, there seems to be no clinical-radiologic correlation given that patients who develop postoperative kyphosis often do not progress to clinical myelopathy. Furthermore, there are specific additional risks of posterior instrumentation that need to be considered.

Conclusion:

In carefully selected patients with normal preoperative cervical sagittal alignment, stand-alone cervical laminectomy may offer acceptably low rates of postoperative kyphosis. In patients with preoperative loss of cervical lordosis and/or kyphosis, posterior fusion is recommended to reduce the risk of progression to postoperative kyphotic deformity, bearing in mind that radiologic evidence of kyphosis may not necessarily correlate with poorer clinical outcomes. Furthermore, the specific risks associated with posterior fusion (instrumentation failure, pseudarthrosis, infection, C5 nerve root palsy, and vertebral artery injury) need to be considered and weighed up against potential benefits.
Gluteus Maximus Transfer for Irreparable Hip Abductor Tendon Tears: Technique and Clinical Outcomes
Authors: Balazs George C. , Dooley Matt , Wang Dean , O’Sullivan Eilish , Gayle Lloyd B. , Kelly Bryan T.
Published: June 2019

Hip abductor tears are increasingly recognized as a common source of lateral hip pain. Primary repair has generally shown excellent results. However, where repair is not possible or advanced muscle atrophy is present, few reconstructive options are available. Here we present the technique and results of a simplified method for transfer of the gluteus maximus tendon to the greater trochanter. Patients undergoing gluteus maximus tendon transfer were identified from our institution hip preservation registry. Electronic health records, imaging, and clinical examination findings were recorded for each patient and analyzed. Preoperative and postoperative patient-reported outcome scores were also collected for each patient including the modified Harris Hip Score (mHHS), Hip Outcome Score-Activity of Daily Living Scale (HOS-ADL), Hip Outcome Score-Sports Scale (HOS-S), and the International Hip Outcome Tool (iHOT-33). Six patients met inclusion criteria. All patients exhibited a Trendelenburg gait before surgery, and mean hip abduction strength preoperatively was 3.8/5. At final clinical follow-up, all patients had 5/5 hip abduction strength on manual muscle testing. No patient experienced a surgical complication. Three of the 6 patients had complete resolution of their Trendelenburg gait. At mean 3.8 years follow-up, mean improvement in HOS-ADL was 16.91, HOS-Sport=24.71, mHHS=18.42, and iHOT-33=42.74.
Association of Elevated Plasma Interleukin-18 Level With Increased Mortality in a Clinical Trial of Statin Treatment for Acute Respiratory Distress Syndrome*
Authors: Rogers Angela J. , Guan Jiazhen , Trtchounian Anna , Hunninghake Gary M. , Kaimal Rajani , Desai Manisha , Kozikowski Lori-Ann , DeSouza Lesley , Mogan Susan , Liu Kathleen D. , Matthay Michael A. , Steingrub Jay , Wheeler Art , Yoon Joo Heon , Nakahira Kiichi , Choi Augustine M. , Baron Rebecca M.
Published: June 2019

Objective:

A high plasma level of inflammasome mediator interleukin-18 was associated with mortality in observational acute respiratory distress syndrome cohorts. Statin exposure increases both inflammasome activation and lung injury in mouse models. We tested whether randomization to statin therapy correlated with increased interleukin-18 in the ARDS Network Statins for Acutely Injured Lungs from Sepsis trial.

Design:

Retrospective analysis of randomized controlled clinical trial.

Setting:

Multicenter North American clinical trial, the ARDS Network Statins for Acutely Injured Lungs from Sepsis.

Patients:

Six hundred eighty-three subjects with infection-related acute respiratory distress syndrome, representing 92% of the original trial population.

Interventions:

Random assignment of rosuvastatin or placebo for up to 28 days or 3 days after ICU discharge.

Measurements and Main Results:

We measured plasma interleukin-18 levels in all Statins for Acutely Injured Lungs from Sepsis patients with sample available at day 0 (baseline, n = 683) and day 3 (after randomization, n = 588). We tested the association among interleukin-18 level at baseline, rising interleukin-18, and the impact of statin therapy on 60-day mortality, adjusting for severity of illness. Baseline plasma interleukin-18 level greater than or equal to 800 pg/mL was highly associated with 60-day mortality, with a hazard of death of 2.3 (95% CI, 1.7–3.1). Rising plasma interleukin-18 was also associated with increased mortality. For each unit increase in log2 (interleukin-18) at day 3 compared with baseline, the hazard of death increased by 2.3 (95% CI, 1.5–3.5). Subjects randomized to statin were significantly more likely to experience a rise in plasma interleukin-18 levels. Subjects with acute kidney injury, shock, low baseline interleukin-18, and those not receiving systemic corticosteroids were more likely to experience rising interleukin-18. Randomization to statin therapy was associated with rising in interleukin-18 in all of those subsets, however.

Conclusions:

Elevated baseline plasma interleukin-18 was associated with higher mortality in sepsis-induced acute respiratory distress syndrome. A rise in plasma interleukin-18 was also associated with increased mortality and was more common in subjects randomized to statin therapy in this clinical trial.
Combination Nivolumab/Ipilimumab Immunotherapy For Melanoma With Subsequent Unexpected Cardiac Arrest: A Case Report and Review of Literature
Authors: Khoury Zaid H. , Hausner Petr F. , Idzik-Starr Cynthia L. , Frykenberg Matthew R.A. , Brooks John K. , Dyalram Donita , Basile John R. , Younis Rania H.
Published: June 2019

The success of immunotherapy in the treatment of patients with advanced melanoma has paved the way for unprecedented successes in the treatment of many other malignancies. We present a case of extensively metastatic oral mucosal melanoma that responded successfully to combined immune checkpoint blockade with ipilimumab and nivolumab but developed multiple immune-related adverse events, including myocarditis, a rare event associated with immunotherapy of elderly melanoma patients. Though the acute myocarditis was managed successfully, the patient succumbed to sudden cardiac death. This case highlights the fact, that autoimmune carditis must be considered when working up the sudden onset of shortness of breath in patients on immune checkpoint blockade. After controlling the acute myocarditis with high-dose steroids, which should be tapered over 6 weeks, further cardiology care is needed, and a defibrillator might have to be implanted. Understanding the pathophysiology of immune-related adverse events could make cancer immunotherapy both more effective and safer.
Predictive Value of Preoperative Periocular Skin Cancer Measurements for Final Mohs Defect Size
Authors: Scofield-Kaplan Stacy M. , Jackson Colette , Gurney Troy , McDonnell Emma , Mancini Ronald
Published: June 2019

The preoperative periocular skin cancer measurements can assist in determining the post-Mohs defect size.

Purpose:

To evaluate the relationship between pre-Mohs skin cancer lesion measurements with the post-Mohs defect size in order to most accurately estimate post-Mohs defect size.

Methods:

This is a retrospective analysis of patients who underwent Mohs excision by one of 3 Mohs surgeons followed by reconstruction for basal cell carcinoma or squamous cell carcinoma of the eyelid. The study included all patients from January 2011 to May 2018 operated on by a single oculoplastic surgeon (R.M.) at the University of Texas Southwestern Medical Center. Maximum horizontal and vertical (H/V) dimensions were determined clinically by Mohs surgeons at the time of excision and photographs of the lesion and defect size were analyzed in order to determine the total area of the lesion preoperatively and the defect postoperatively with Image J using H/V dimensions and the area tracing function.

Results:

Forty-two patients with periocular skin cancers underwent Mohs resection followed by reconstruction. The Mohs defect was overall 4.88 times the size of the preoperative skin cancer measurement using maximum H/V dimensions by Mohs surgeons (p < 0.0001). When using Image J, the area of the Mohs defect was 6.5 times the size of the preoperative lesion (p < 0.0001) using both the maximum H/V dimensions and the area tracing function. There was a statistically significant difference between the Image J area tracing and area determined with H/V dimensions by both the Mohs surgeon and Image J.

Conclusions:

Postoperative Mohs defect size can be estimated based on maximum H/V dimensions clinically or with Image J technology. Image J digital photograph analysis using the area tracing function more accurately determines the pre-Mohs lesion size and the post-Mohs defect area when compared with standard maximum H/V measurements and digital photographic analysis of maximum H/V measurements with Image J.
Next-Generation Sequencing in Pancreatic Cancer
Authors: Shen Gong-Qing , Aleassa Essa M. , Walsh R. Matthew , Morris-Stiff Gareth
Published: June 2019

Pancreatic ductal adenocarcinoma (PDAC) is lethal, and the majority of patients present with locally advanced or metastatic disease that is not amenable to cure. Thus, with surgical resection being the only curative modality, it is critical that disease is identified at an earlier stage to allow the appropriate therapy to be applied. Unfortunately, a specific biomarker for early diagnosis has not yet been identified; hence, no screening process exists. Recently, high-throughput screening and next-generation sequencing (NGS) have led to the identification of novel biomarkers for many disease processes, and work has commenced in PDAC. Genomic data generated by NGS not only have the potential to assist clinicians in early diagnosis and screening, especially in high-risk populations, but also may eventually allow the development of personalized treatment programs with targeted therapies, given the large number of gene mutations seen in PDAC. This review introduces the basic concepts of NGS and provides a comprehensive review of the current understanding of genetics in PDAC as related to discoveries made using NGS.
KRAS in Cyst Fluid Obtained by Endoscopic Ultrasound–Fine-Needle Aspiration in Pancreatic Cystic Lesions
Authors: Faias Sandra , Pereira Luisa , Luís Ângelo , Cravo Marília , Dias Pereira António , Torres Joana
Published: June 2019

To evaluate the diagnostic accuracy of KRAS mutation in pancreatic cystic fluid and compare it with carcinoembryonic antigen and cytology, we identified studies with cyst fluid obtained by endoscopic ultrasound prior to surgery. We classified cysts as malignant, premalignant, and benign. A random-effects model was used for quantitative meta-analysis. Pooled sensitivities, specificities, and summary receiver operating characteristic curve analysis were conducted. We analyzed 16 studies, with 3429 patients, including 731 referred for surgery. Carcinoembryonic antigen was better for clinically significant cysts (premalignant and malignant) with sensitivity = 0.58 (95% confidence interval [CI], 0.53–0.65), specificity = 0.9 (95% CI, 0.76–0.97), and area under the curve (AUC) = 0.69. Cytology performed better in malignant cysts, with sensitivity = 0.37 (95% CI, 0.27–0.48), specificity = 0.96 (95% CI, 0.93–0.98), and AUC = 0.78. Isolated, KRAS mutation failed the diagnosis of malignant and significant cysts, with sensitivities = 0.43 (95% CI, 0.34–0.43) and 0.46 (95% CI, 0.42–0.51), specificities = 0.62 (95% CI, 0.56–0.68) and 0.97 (95% CI, 0.92–0.99), and AUCs = 0.56 and 0.53, respectively. Carcinoembryonic antigen and cytology are more accurate than KRAS. Additional studies are lacking to recommend KRAS as a single diagnostic test.
HPV-negative Tumors in a Swedish Cohort of Cervical Cancer
Authors: Kaliff Malin , Karlsson Mats G. , Sorbe Bengt , Bohr Mordhorst Louise , Helenius Gisela , Lillsunde-Larsson Gabriella
Published: June 2019

Despite the common perception that the human papilloma virus (HPV) is a requirement for the development of cervical cancer (CC), a considerable number of CCs test HPV negative. Presently, many countries are shifting to HPV primary CC screening, and it is of importance to increase the knowledge about the group of CCs that test HPV negative. The aim of this study was to reinvestigate a proportion of cervical tumors with a primary negative or invalid test result. Reinvestigation with repeated genotyping (targeting L1) was followed by analysis with an alternative target method (targeting E6/E7) on existing or additional tumor material. Consistently negative tumors were histologically evaluated, and cases with low or lacking tumor cell content, consistent invalid test results, or with suspicion of other than cervical origin were excluded. HPV-negative cases were thereafter subjected to immunohistochemistry (Cytokeratin 5, pan cytokeratin, protein 63, P16, and P53). The HPV-negative proportion could after reinvestigation be reduced by one-half (14%–7%). Additional positive samples were often detected in late polymerase chain reaction cycles, with an alternative (E6/E7) or the same (L1) target, or with a method using shorter amplicon lengths. Confirmed HPV negativity was significantly associated with worse prognosis, high patient age, longer storage time, and adenocarcinoma histology. Some of the HPV-negative cases showed strong/diffuse p16 immunoreactivity, indicating some remaining false-negative cases. False HPV negativity in this cohort was mainly linked to methodological limitations in the analysis of stored CC material. The small proportion of presumably true HPV-negative adenocarcinomas is not a reason for hesitation in revision to CC screening with primary HPV testing.
Innovative and Contemporary Interventions of Diaphragmatic Disorders
Authors: Black Matthew C. , Joubert Kyla , Seese Laura , Ocak Iclal , Frazier Aletta A. , Sarkaria Inderpal , Strollo Diane C. , Sanchez Manuel V.
Published: June 2019

The diaphragm is an inconspicuous fibromuscular septum, and disorders may result in respiratory impairment and morbidity and mortality when untreated. Radiologists need to accurately diagnose diaphragmatic disorders, understand the surgical approaches to diaphragmatic incisions/repairs, and recognize postoperative changes and complications. Diaphragmatic defects violate the boundary between the chest and abdomen, with the risk of herniation and strangulation of abdominal contents. In our surgical practice, patients with diaphragmatic hernias present acutely with incarceration and/or strangulation. Bochdalek hernias are commonly diagnosed in asymptomatic older adults on computed tomography; however, when viscera or a large amount of fat herniates into the chest, surgical intervention is strongly advocated. Morgagni hernias are rare in adults and typically manifest acutely with bowel obstruction. Patients with traumatic diaphragm injury may have an acute, latent, or delayed presentation, and radiologists should be vigilant in inspecting the diaphragm on the initial and all subsequent thoracoabdominal imaging studies. Almost all traumatic diaphragm injury are surgically repaired. Finally, with porous diaphragm syndrome, fluid, air, and tissue from the abdomen may communicate with the pleural space through diaphragmatic fenestrations and result in a catamenial pneumothorax or large pleural effusion. When the underlying disorder cannot be effectively treated, the goal of surgical intervention is to establish the diagnosis, incite pleural adhesions, and close diaphragmatic defects. Diaphragmatic plication may be helpful in patients with eventration or acquired injuries of the phrenic nerve, as it can stabilize the affected diaphragm. Phrenic nerve pacing may improve respiratory function in select patients with high cervical cord injury or central hypoventilation syndrome.
Interventional Therapies for Thoracic Duct Injury and Intractable Chylothorax
Authors: Novelli Paula M. , Chan Ernest G. , Frazier Aletta A. , Villa Sanchez Manuel
Published: June 2019

Injury to the thoracic duct with resultant chylothorax can cause significant patient morbidity and mortality. Conservative treatment strategies often fail to address the problem. Open surgical and percutaneous approaches are often required to manage patients with refractory chylothorax. This review describes in detail the major role of minimally invasive interventional therapies for thoracic duct (TD) injury. The review emphasizes strategies for identifying the TD on preprocedural imaging and describes various techniques for percutaneous access to the TD. The advantages and disadvantages of several approaches for accessing the duct are discussed. The technique of duct embolization is highlighted. The role of the minimally invasive percutaneous approach over open surgical approaches is discussed with a review of clinical outcomes, as reported in the literature. This review will also briefly discuss the surgical approach to TD ligation.
Imaging-guided Percutaneous Biopsy of Nodules ≤1 cm
Authors: Portela de Oliveira Eduardo , Souza Carolina A. , Inacio Joao R. , Abdelzarek Mohamed , Dennie Carole , Gupta Ashish , Bayanati Hamid
Published: June 2019

Objective:

Percutaneous biopsy of lung nodules is established as a safe procedure with high diagnostic yield and accuracy. Its role in the diagnosis of subcentimeter nodules is, however, less clear. The goal of this study was to evaluate diagnostic yield, accuracy, and safety of computed tomography (CT)-guided needle biopsy in the diagnosis of subcentimeter lung nodules.

Material and Methods:

A retrospective review of a prospectively maintained database over a 12-year period identified 133 eligible CT-guided needle biopsies of lesions ≤1 cm. Diagnostic yield and accuracy for the diagnosis of malignancy were calculated. Lesion features and procedure characteristics were assessed using univariate and multivariate logistic regression analysis to identify risk factors associated with biopsy failure and complications.

Results:

Biopsy specimens were adequate for diagnosis in 116/133(87%) cases; the diagnostic yield for malignant and benign lesions was 93% and 65%, respectively. Final benign diagnosis was the strongest independent risk factor for biopsy failure. In multivariate logistic regression, fine-needle aspiration was an independent risk factor for diagnostic failure. Core needle biopsy was an independent risk factor for pneumothorax, and core needle biopsy, number of passes, and age were independent risk factors for pneumothorax requiring tube drainage.

Conclusions:

CT-guided percutaneous needle biopsy had high diagnostic yield for the diagnosis of subcentimeter lung nodules with a similar complication rate to biopsy of larger lesions. Fine-needle aspiration may be an independent factor for diagnostic failure even for malignant lesions.
Will giant polar amphipods be first to fare badly in an oxygen-poor ocean? Testing hypotheses linking oxygen to body size
Authors: Spicer John I. , Morley Simon A.
Published: June 2019

It has been suggested that giant Antarctic marine invertebrates will be particularly vulnerable to declining O
2
levels as our ocean warms in line with current climate change predictions. Our study provides some support for this oxygen limitation hypothesis, with larger body sizes being generally more sensitive to O
2
reductions than smaller body sizes. However, it also suggests that the overall picture is a little more complex. We tested predictions from three different, but overlapping, O
2
-related hypotheses accounting for gigantism, using four Antarctic amphipod species encompassing a wide range of body sizes. We found a significant effect of body size, but also of species, in their respiratory responses to acutely declining O
2
tensions. The more active lifestyle of intermediate-sized
Prostebbingia brevicornis
was supported by a better respiratory performance than predicted by the oxygen limitation hypothesis alone, but consistent with the symmorphosis hypothesis. We suggest that giant polar amphipods are likely to be some of the first to fare badly in an O
2
-poor ocean. However, the products of past evolutionary innovation, such as respiratory pigments that enhance O
2
-transport and novel gas exchange structures, may in some species offset any respiratory disadvantages of either large or small body size.

This article is part of the theme issue ‘Physiological diversity, biodiversity patterns and global climate change: testing key hypotheses involving temperature and oxygen’.
A yeast optogenetic toolkit (yOTK) for gene expression control in Saccharomyces cerevisiae
Authors: An-adirekkun Jidapas (My) , Stewart Cameron J. , Geller Stephanie H. , Patel Michael T. , Melendez Justin , Oakes Benjamin L. , Noyes Marcus B. , McClean Megan N.
Published: June 2019

Optogenetic tools for controlling gene expression are ideal for tuning synthetic biological networks due to the exquisite spatiotemporal control available with light. Here we develop an optogenetic system for gene expression control and integrate it with an existing yeast toolkit allowing for rapid, modular assembly of light-controlled circuits in the important chassis organism Saccharomyces cerevisiae. We reconstitute activity of a split synthetic zinc-finger transcription factor (TF) using light-induced dimerization. We optimize function of this split TF and demonstrate the utility of the toolkit workflow by assembling cassettes expressing the TF activation domain and DNA-binding domain at different levels. Utilizing this TF and a synthetic promoter we demonstrate that light-intensity and duty-cycle can be used to modulate gene expression over the range currently available from natural yeast promoters. This work allows for rapid generation and prototyping of optogenetic circuits to control gene expression in Saccharomyces cerevisiae.
Horizontal transfer and gene loss shaped the evolution of alpha-amylases in bilaterians
Authors: Desiderato Andrea , Barbeitos Marcos , Gilbert Clément , Da Lage Jean-Luc
Published: June 2019

The subfamily GH13_1 of alpha-amylases is typical of Fungi, but it is also found in some unicellular eukaryotes (e.g. Amoebozoa, choanoflagellates) and non-bilaterian Metazoa. Since a previous study in 2007, GH13_1 amylases were considered ancestral to the Unikonts, including animals, except Bilateria, such that it was thought to have been lost in the ancestor of this clade. The only alpha-amylases known to be present in Bilateria so far belong to the GH13_15 and 24 subfamilies (commonly called bilaterian alpha-amylases) and were likely acquired by horizontal transfer from a proteobacterium. The taxonomic scope of Eukaryota genomes in databases has been greatly increased ever since 2007. We have surveyed GH13_1 sequences in recent data from ca. 1600 bilaterian species, 60 non-bilaterian animals and also in unicellular eukaryotes. As expected, we found a number of those sequences in non-bilaterians: Anthozoa (Cnidaria) and in sponges, confirming the previous observations, but none in jellyfishes and in Ctenophora. Our main and unexpected finding is that such fungal (also called Dictyo-type) amylases were also consistently retrieved in several bilaterian phyla: hemichordates (deuterostomes), brachiopods and related phyla, some molluscs and some annelids (protostomes). We discuss evolutionary hypotheses possibly explaining the scattered distribution of GH13_1 across bilaterians, namely, the retention of the ancestral gene in those phyla only and/or horizontal transfers from non-bilaterian donors.
SMNN: Batch Effect Correction for Single-cell RNA-seq data via Supervised Mutual Nearest Neighbor Detection
Authors: Yang Yuchen , Li Gang , Qian Huijun , Wilhelmsen Kirk C. , Shen Yin , Li Yun
Published: June 2019

Batch effect correction has been recognized to be indispensable when integrating single-cell RNA sequencing (scRNA-seq) data from multiple batches. State-of-the-art methods ignore single-cell cluster label information, but such information can improve effectiveness of batch effect correction, particularly under realistic scenarios where biological differences are not orthogonal to batch effects. To address this issue, we propose SMNN for batch effect correction of scRNA-seq data via supervised mutual nearest neighbor detection. Our extensive evaluations in simulated and real datasets show that SMNN provides improved merging within the corresponding cell types across batches, leading to reduced differentiation across batches over MNN, Seurat v3, and LIGER. Furthermore, SMNN retains more cell type-specific features, partially manifested by differentially expressed genes identified between cell types after SMNN correction being biologically more relevant, with precision improving by up to 841%.

Key Points

Batch effect correction has been recognized to be critical when integrating scRNA-seq data from multiple batches due to systematic differences in time points, generating laboratory and/or handling technician(s), experimental protocol, and/or sequencing platform.

Existing batch effect correction methods that leverages information from mutual nearest neighbors across batches (for example, implemented in SC3 or Seurat) ignore cell type information and suffer from potentially mismatching single cells from different cell types across batches, which would lead to undesired correction results, especially under the scenario where variation from batch effects is non-negligible compared with biological effects.

To address this critical issue, here we present SMNN, a supervised machine learning method that first takes cluster/cell-type label information from users or inferred from scRNA-seq clustering, and then searches mutual nearest neighbors within each cell type instead of global searching.

Our SMNN method shows clear advantages over three state-of-the-art batch effect correction methods and can better mix cells of the same cell type across batches and more effectively recover cell-type specific features, in both simulations and real datasets.