bluuebunny/crossref_metadata_2025 huggingface dataset:
Placental Growth Factor Testing to Assess Women With Suspected Preeclampsia: A Multicentre, Pragmatic, Stepped-wedge Cluster-randomized Controlled Trial
Authors: Duhig K.E. , Myers J. , Seed P.T. , Sparkes J. , Lowe J. , Hunter R.M. , Shennan A.H. , Chappell L.C.
Published: February 2020

(Lancet. 2019;393:1807–1818)

Approximately 3% of singleton pregnancies are affected by preeclampsia, which can be difficult to diagnose as many women are asymptomatic. Hypertension and increased urinary protein excretion are common factors used to establish the diagnosis, but there are challenges in testing and observing both of these features. The pathophysiology of preeclampsia involves angiogenic factors, and low circulating maternal placental growth factor (PlGF) concentrations have been found to be useful in the diagnosis of preeclampsia with high sensitivity and negative predictive value. However, this potential tool for diagnosing preeclampsia should first be tested in a real-world setting to understand both its practical benefits and challenges. This study aimed to determine whether a preeclampsia diagnosis could be more quickly reached in women with suspected preeclampsia by incorporating measurement of the PlGF circulating concentration into an already established clinical management algorithm. The study also investigated the effect of using this diagnostic approach on maternal and perinatal outcomes.
Comparison of the Potency of Phenylephrine and Norepinephrine Bolus Doses Used to Treat Postspinal Hypotension During Elective Cesarean Section
Authors: Mohta M. , Dubey M. , Malhotra R.K. , Tyagi A.
Published: February 2020

(Int J Obst Anesth. 2019;38:25–31)

Vasopressors to manage hypotension after spinal anesthesia are commonly used in obstetric patients. Phenylephrine has been considered the vasopressor of choice for many years, but it can result in reflex bradycardia and an associated fall in cardiac output. Norepinephrine is another potent vasopressor that has significant chronotropic effects that should limit bradycardia. However, there is little information about the preferred dose for managing postspinal hypotension in obstetric patients or its potency ratio compared with phenylephrine. This study aimed to calculate the 95% and 50% effective doses (ED95 and ED50) of both drugs and their potency ratio when administered as a bolus for the treatment of spinal-induced hypotension in women undergoing elective cesarean section.
Right Heart Masses Demonstrated by Echocardiography in a Patient With Amniotic Fluid Embolism During Labour
Authors: Maack K.H. , Munk K. , Dahl K. , Jørgensen H.H. , Christiansen A. , Helmig R.B.
Published: February 2020

(Acta Anaesthesiol Scand. 2018;62(1):134–137)

This case report described a patient in active labor after an oral misoprostol induction. While initial vital signs of the patient and fetus were normal, membranes unexpectedly ruptured and the patient became unresponsive. The maternal pulse was not detected in the operating room, so care providers delivered a live male infant by cesarean section to facilitate resuscitation of the patient. Ultrasound imaging showed the inferior vena cava contained large masses protruding into the right atrium, through the tricuspid valve and into the right ventricle. Cardiovascular circulation was restored 12 minutes after cardiovascular collapse, and epinephrine was administered to assist with circulation stabilization. Observation through echocardiography showed the masses gradually disappeared and the right ventricle became a normal size again. Because of a high volume of blood loss, care providers performed a red blood cell and plasma transfusion before the patient was transferred to the intensive care unit (ICU). Disseminated intravascular coagulation was suspected and later confirmed through blood analyses.
Case 25-2019: A 41-Year-Old Pregnant Woman With Abdominal Pain
Authors: Saillant N.N. , Kilcoyne A. , Fagenholz P.J. , Lui R. , Krystel-Whittemore M.
Published: February 2020

(N Engl J Med. 2019;381(7):656–664)

A 41-year-old women presented to the emergency room at 36 weeks and 3 days of gestation, complaining of abdominal pain. The pain was in the right lower quadrant and described as sharp and constant. She rated the pain at 8 on a 0 to 10 scale, with 10 indicating the most severe pain. The patient had had 4 previous pregnancies—2 were uncomplicated vaginal deliveries and 1 ended in spontaneous abortion. For her current pregnancy, her initial prenatal visit was normal and prenatal follow-up had been uneventful. Her obstetrician referred her to the clinic, where a transabdominal and transvaginal ultrasonography indicated no abnormal fetal findings. The patient was referred to another hospital’s emergency department.
Gonorrhea-positive sinus cultures in a 15-year-old with allergic fungal sinusitis
Authors: Donner Kimberly , Kou Yann-Fuu , Tomkies Anna , Rakheja Dinesh , Mitchell Ron B. , Shah Gopi
Published: February 2020

This article describes a patient with gonorrhea in sinus cultures and allergic fungal sinusitis. A multidisciplinary team was assembled to deliver the results to the minor patient and her family and provide support and resources for long-term care.
Historical Perspective of Proactive and Reactive Regulations of E-cigarettes to Combat Nicotine Addiction
Authors: Gholap Vinit , Halquist Matthew S.
Published: February 2020

Cigarettes and electronic cigarettes (e-cigarettes) are major sources of exposure to nicotine, an addictive chemical. Although these products are being regulated by the Food and Drug Administration (FDA) under the Tobacco Control Act, specifications about the nicotine content in these products have not been established yet. In e-cigarettes, nicotine concentration ranges from 0 to > 50mg/mL, and the recent e-cigarette devices provide control to change nicotine flux for higher nicotine delivery. Due to the lack of robust regulations in manufacturing, distribution and marketing, e-cigarettes have already infiltrated the market with youth appealing flavors and devices. As a result, the country is facing a youth epidemic of e-cigarette use. The unregulated nicotine levels in both cigarettes and e-cigarettes can lead to repeated and overexposure of nicotine to youth which can lead to the addiction and detrimental effects on their cognitive functions. Over the past decade, the corrective measures being taken by the FDA for cigarette and e-cigarette regulations also should focus on nicotine exposure levels. Before it is too late to prevent youth from lifetime addiction to nicotine, it is important to address the issues of nicotine concentration, nicotine flux and the e-cigarette device regulations while offering adults with smoking disorder less harmful alternatives to cigarettes.
Minimally Invasive Medial Plate Osteosynthesis of High-Energy Pediatric Tibia Fractures
Authors: Murphy Michael , Killen Cameron , Lynch Kyle , Cohen Joseph , Summers Hobie , Stover Michael , Lack William
Published: February 2020

Objectives:

We report on the largest series to date of minimally invasive medial plate osteosynthesis of high-energy tibia fractures in skeletally immature patients.

Design:

Retrospective.

Setting:

Level 1 trauma center.

Patients:

Skeletally immature patients with high-energy tibia fractures treated with minimally invasive medial plate osteosynthesis between 2006 and 2017. We identified 28 fractures in 26 patients.

Main Outcome Measure:

We reviewed the record for patient, injury, and treatment factors as well as for complications and reoperation. We assessed the relationships between age, implant selection, and implant removal using χ2 and t test analyses.

Results:

Mean age was 12 years (4–15) with OTA/AO classifications including 42A (18), 42B (6), and 42C (4). There were 10 open fractures (1 type I, 2 type II, and 7 type III). Mean follow-up was 37.6 months (minimum 7). Mean time to full weight-bearing and union was 2 and 3 months, respectively. Plate stock (2.7, 3.5, and 4.5 mm) and length (6–20 holes) varied independent of age, P = 0.19. There were 2 superficial infections, one 15 mm leg length discrepancy, and one case of fasciotomy at the time of plate fixation for trauma-related compartment syndrome. Implant removal was more likely in younger patients (10.9 vs. 13.2 years, P = 0.04) and not associated with plate stock, P = 0.97. There were no neurovascular injuries, losses of reduction, or rotational deformities. Angulation was universally <5 degrees in the coronal plane and <10 degrees in the sagittal plane.

Conclusions:

Minimally invasive medial plate osteosynthesis of high-energy pediatric tibia fractures may be performed with a low rate of complications and should be considered in this select patient population with multiple injuries, high-energy mechanisms, and significant soft-tissue trauma.

Level of Evidence:

Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
90-day Readmission Rates for Single Level Anterior Lumbosacral Interbody Fusion
Authors: Elia Christopher J. , Arvind Varun , Brazdzionis James , von Glinski Alexander , Schell Benjamin A. , Pierre Clifford A. , Ogunlade John , Chapman Jens R. , Oskouian Rod J.
Published: February 2020

Study Design.

Nationwide Readmissions Database Study.

Objective.

To investigate the patterns of readmissions and complications following hospitalization for elective single level anterior lumbobsacral interbody fusion.

Summary of Background Data.

Lumbar interbody spine fusions for degenerative disease have increased annually in the United States, including associated hospital costs. Anterior lumbar interbody fusions (ALIFs) have become popularized secondary to higher rates of fusion compared with posterior procedures, and preservation of posterior elements. Prior national databases have sought to study readmission rates with some limitations due to older diagnosis and procedure codes. The newer 2016 International Classification of Diseases Tenth Revision, Clinical Modification (ICD-10 CM) includes more specification of the surgical site.

Methods.

We utilized the 2016 United States Nationwide Readmissions Database (NRD), this nationally representative, all-payer database that includes weighted probability sample of inpatient hospitalizations for all ages. We identified all adults (≥ 18 yrs) using the 2016 ICD-10 coding system who underwent elective primary L5-S1 ALIF and examined rates of readmissions within 90 days of discharge.

Results.

Between January and September 2016, a total of 7029 patients underwent elective stand-alone L5-S1 ALIF who were identified from NRD of whom 497 (7.07%) were readmitted within 90 days of their procedure. No differences in sex were appreciated. Medicare patients had statistically significant higher readmission rates (47.69%) among all payer types. With respect to intraoperative complications, vascular complications had statistically significant increased odds of readmission (OR, 3.225, 95% CI, 0.59 –1.75; P = 0.0001). Readmitted patients had higher total healthcare costs.

Conclusion.

The 90-day readmission rate following stand-alone single level lumbosacral (L5-S1) ALIF was 7.07%. ALIF procedures have increased in frequency, and an understanding of the comorbidities, age-related demographics, and costs associated with 90-day readmissions are critical. Surgeons should consider these risk factors in preoperative planning and optimization.

Level of Evidence: 3
Duration and Dosage of Opioids After Spine Surgery
Authors: Hills Jeffrey M. , Carlile Catherine R. , Archer Kristin R. , Wick Joseph B. , Butler Marjorie , Daryoush Joshua , Khan Inamullah , Call Richard , Devin Clinton J. , Pennings Jacquelyn S.
Published: February 2020

Study Design.

Longitudinal Cohort Study

Objective.

The aim of this study was to determine whether duration of postoperative opioids is associated with long-term outcomes, and if initial postoperative opioid dosage is associated with opioid cessation after spine surgery.

Summary of Background Data.

Preoperative opioid use is associated with poor outcomes, but little evidence exists regarding the implications of opioid dosage and duration after spine surgery.

Methods.

Data from our state's prescription drug database was linked to our prospective clinical spine registry to analyze opioid dispensing and outcomes in elective surgical spine patients between 2010 and 2017. Patients were stratified based on preoperative chronic opioid use and multivariable regression was used to assess associations between duration of postoperative opioids and outcomes at one year, including satisfaction, chronic opioid use, and meaningful improvements in pain, disability, and quality of life. In a secondary aim, a Cox proportional hazards model was used to determine whether initial postoperative opioid dosage was associated with time to opioid cessation.

Results.

Of 2172 patients included, 35% had preoperative chronic opioid use. In patients without preoperative chronic opioid use, a postoperative opioid duration of 31 to 60 days was associated with chronic opioid use at 1 year (adjusted odds ratio [aOR]: 4.1 [1.7–9.8]) and no meaningful improvement in extremity pain (aOR: 1.8 [1.3–2.6]) or axial pain (aOR: 1.6 [1.1–2.2]); cessation between 61 and 90 days was associated with no meaningful improvement in disability (aOR: 2 [1.3–3]) and dissatisfaction (aOR:1.8 [1–3.1]). In patients with preoperative chronic opioid use, postoperative opioids for ≥90 days was associated with dissatisfaction. Cox regression analyses showed lower initial postoperative opioid dosages were associated with faster opioid cessation in both groups.

Conclusion.

Our results suggest that a shorter duration of postoperative opioids may result in improved 1-year patient-reported outcomes, and that lower postoperative opioid dosages may lead to faster opioid cessation.

Level of Evidence: 2
Effects of Specific Exercise Therapy on Adolescent Patients With Idiopathic Scoliosis
Authors: Liu Delong , Yang Yunlin , Yu Xuexiang , Yang Jingfan , Xuan Xiaoling , Yang Junlin , Huang Zifang
Published: February 2020

Study Design.

A prospective controlled cohort study.

Objective.

The aim of this study was to explore the interventional effect of exercise therapy on idiopathic scoliosis (IS) and identify an optimal intervention window.

Summary of Background Data.

Early conservative treatment is helpful for IS. In addition to bracing, current evidence suggests that exercise can play an important role.

Methods.

We included 99 patients with IS who were treated at the Guangdong Xinmiao Scoliosis Center from August 2013 to September 2017. The inclusion criteria were: new IS diagnosis, Cobb angle 10° to 25°, Risser 0 to 3 grade, only treated with the Xinmiao treatment system (XTS; >3 days/week, >1 h/day), and follow-up >1 year. Patients were divided into three age groups: A, <10 years (n = 29); B, 10 to 12 years (n = 24); and C, 13 to 15 years (n = 46). The percentages of curve improvement (Cobb angle decrease ≥5°), stability (Cobb angle change × ±5°), and progression (Cobb angle increase ≥5°) were compared.

Results.

The groups showed significant differences for major curve correction, Risser sign, first referral, and final follow-up of the main curve (all P < 0.05). The major curve in group A decreased significantly by 6.8° (44% correction), compared to 3.1° (18% correction) and 1.5° (9% correction) in groups B and C, respectively. In group A, 69.0% (20/29) had curve improvement, 27.6% (8/29) stabilized and 3.4% (1/29) progressed. In group B, 45.8% (11/24) improved, 50% (12/24) stabilized, and 4.2% (1/24) progressed. In group C, 26.1% (12/46) improved, 63.0% (29/46) stabilized, and 10.9% (5/46) progressed. There was also a significant difference in final Risser grade among the groups (P < 0.05).

Conclusion.

For IS patients with Cobb angles between 10° and 25°, our exercise protocol can effectively control or improve curve progression. Younger patients with a lower Risser grade are most likely to respond.

Level of Evidence: 2
Activation of muscarinic acetylcholine receptor 1 promotes invasion of hepatocellular carcinoma by inducing epithelial-mesenchymal transition
Authors: Zhang Liang , Wu Li-Li , Huan Hong-Bo , Wen Xu-Dong , Yang Da-Peng , Chen Dong-Feng , Xia Feng
Published: February 2020

Hepatocellular carcinoma is the second leading cause of cancer-related death worldwide. Neural regulation plays an important role in the development of hepatocellular carcinoma, and activation of sympathetic nervous system can promote the migration and invasion of cancer cells. However, little research has been conducted on how the vagus nerve influences hepatocellular carcinoma. In this study, we found that the expression of vesicular acetylcholine transporter, a biomarker of vagus nerve, was associated with hepatocellular carcinoma patients’ clinicopathological characteristics by immunohistochemistry. Further, activation of muscarinic acetylcholine receptor 1 (M1R) promoted HepG2 and SMMC-7721 cells migration and invasion and epithelial-mesenchymal transition via PI3K/Akt pathway. Moreover, inhibition of M1R by antagonist or shRNA suppressed hepatocellular carcinoma cells migration and invasion in vitro and in vivo, inhibited epithelial-mesenchymal transition and PI3K/Akt pathway. Therefore, these results indicate that activation of M1R promotes invasion of hepatocellular carcinoma through epithelial-mesenchymal transition and PI3K/Akt pathway.
Frequency and Cause of Readmissions in Sepsis Patients Presenting to a Tertiary Care Hospital in a Low Middle Income Country
Authors: Arshad Ainan , Ayaz Ahmed , Haroon Mian Arsam , Jamil Bushra , Hussain Erfan
Published: February 2020

Objectives:

Hospital readmissions are known to be common after sepsis but unfortunately, in a developing country like Pakistan, very little is known of the frequency or cause of these readmissions in sepsis patients and even less about how they can be prevented. To our knowledge, this is the first-ever long-term follow-up study in a developing country in which frequency and cause of readmissions are being evaluated in sepsis patients.

Design:

This retrospective study evaluated sepsis patients admitted at the Aga Khan University Hospital in 2017. Outcome measures included in-hospital mortality and readmission within 180 days.

Setting:

Aga Khan University Hospital, Karachi, Pakistan.

Subjects:

Four-hundred thirty-nine sepsis patients.

Interventions:

None.

Measurements and Main Results:

Respiratory infections were the most common cause of sepsis (172 [39%]) followed by urinary tract infections (86 [20%]). Mortality in sepsis was 42% (183/439) and associated risk factors included ICU admission (odds ratio, 1.57; 95% CI, 1.05–2.35; p = 0.027), malignancy(odds ratio, 3.50; 95% CI, 1.70–7.19; p = 0.001), acute kidney injury (odds ratio, 1.86; 95% CI, 1.25–2.77; p = 0.002), septic shock (odds ratio, 4.75; 95% CI, 3.04–7.35; p = 0.001), and serum lactate greater than or equal to 4 mmol (odds ratio, 5.11; 95% CI, 3.00–8.73; p = 0.001). Of the 256 patients that survived, 31% (79/256) were readmitted within 180 days. Infections accounted for 67% (53/79) of these readmissions. Half of these infections were new infections while an additional 26% were unclear since cultures were negative in at least one of the hospitalizations.

Conclusions:

We concluded that mortality rates in sepsis are alarmingly high and even those who manage to survive are still at a great risk of getting readmitted due to a new infection in the near future. Given the limited resources available in developing countries, prevention of these infections should be given utmost importance. Unfortunately, reliable interventions to identify high-risk patients for readmissions are still inadequately characterized. Hence, we hope this study becomes a platform for larger multicenter studies in developing countries for early prediction of potential readmissions and developing precise interventions to prevent them.
Comparison of cell salvage with one and two suction devices during cesarean section in patients with placenta previa and/or accrete: a randomized controlled trial
Authors: Chen Hong , Tan Hua , Luo Pei-Xin , Shen Yi-Fang , Lyu Chang-Cheng , Qian Xiao-Wei , Chen Xin-Zhong
Published: February 2020

Background

Cell salvage has recently been recommended for obstetric use in cases with a high risk of massive hemorrhage during cesarean section (CS). However, limited data are available to support the use of one suction device to collect lost blood. This study aimed to investigate the volume of red blood cells (RBCs) salvaged and the components of amniotic fluid (AF) in blood salvaged by one suction device or two devices during CS in patients with placenta previa and/or accrete.

Methods

Thirty patients with placenta previa and/or accrete undergoing elective CS in the Women's Hospital of Zhejiang University School of Medicine were recruited for the present study from November 1, 2017 to December 1, 2018. The patients were randomly assigned to one of the two groups according to an Excel-generated random number sheet: Group 1 (n = 15), in which only one suction device was used to aspirate all blood and AF, and Group 2 (n = 15), in which a second suction device was mainly used to aspirate AF before the delivery of the placenta. Three samples of blood per patient (pre-wash, post-wash, and post-filtration) were collected to measure AF components. The salvaged RBC volumes were recorded. Continuous data of pre-wash, post-wash, and post-filtration samples were analyzed by using one-way analysis of variance with Tukey's test for multiple comparisons, or Kruskal-Wallis test with Dunn test for multiple comparisons. Comparisons of continuous data between Group 1 and Group 2 were conducted using Student's t test or Mann-Whitney U test.

Results

The salvaged RBC volume was significantly higher in Group 1 than that in Group 2 (401.6 ± 77.2 mL vs. 330.1 ± 53.3 mL, t = 4.175, P < 0.001). In both groups, squamous cells, lamellar bodies, and fat were significantly reduced by washing (all P<0.001) and squamous cells were further reduced by filtering (P < 0.001). Squamous cells were found in six post-filtration samples (three from each group). Lamellar bodies and fat were completely removed by filtering. Insulin-like growth factor binding protein 1, alpha-fetoprotein, albumin, lactate dehydrogenase, and potassium were significantly reduced post-wash (all P < 0.05), with no further significant reduction after filtration in either group (all P > 0.05). The mean percentage of fetal RBCs post-filtration was (1.8 ± 0.8)% with a range of 1.0% to 3.5% and (1.9 ± 0.9)% with a range of 0.7% to 4.0% in Groups 1 and 2, respectively, showing no significant difference between the two groups (U = 188.5, P = 0.651).

Conclusion

Cell salvage performed by one suction device could result in higher volume of salvaged RBCs and can be used safely for CS in patients with placenta previa and/or accrete when massive hemorrhage occurs.

Trial registration number

ChiCTR-INR-17012926, http://www.chictr.org.cn/ Chinese Clinical Trial Registry.
Nipple-sparing Mastectomy and Ptosis: Using a Free Nipple Graft with Tissue Expander Reconstruction
Authors: Ghidei Luwam , Bansil Hannah A. , Stuckey Ashley , Pandya Sonali , Edmonson David , Michaud Pierre , Gass Jennifer
Published: February 2020

Background:

Nipple-sparing mastectomies are increasingly offered to women with breast cancer given the evidence for oncologic safety and improved cosmetic outcomes. Women with significant ptosis are often excluded due to potential nipple malposition and increased risk of nipple ischemia. The use of a harvested free nipple graft may allow women with ptosis to conserve their nipple -areolar complex.

Methods:

This is an IRB approved retrospective study of breast cancer patients at an academic center with ptosis who underwent free-nipple graft mastectomies with a single plastic surgeon and 5 dedicated breast surgeons from 2014-2017. The primary outcomes were free nipple graft viability and the need for revision. Secondary outcomes included post-operative complications.

Results:

Fourteen women with ptosis underwent skin and nipple-sparing mastectomy with breast reconstruction involving use of harvested free-nipple graft. More than half of the women were diagnosed with early-stage invasive breast cancer (42% stage 1, 14% stage 2). Four women underwent mastectomy for prophylaxis or other benign reasons. All of the women had significant ptosis during the pre-operative evaluation (57% grade 2 ptosis, 36% grade 3 ptosis, and 7% uncategorized), with an average BMI of 30. None were active smokers. In the postoperative period, one had partial nipple necrosis in combination with skin flap necrosis and positive margin (7%). Other complications included infection (14%) and hypopigmentation (14%). All nipples lost sensation and full projection.

Conclusions:

This is a novel approach using a free nipple graft with a skin envelope reducing mastectomy and immediate expander-based reconstruction. This successful approach allows women with ptosis to undergo nipple-sparing mastectomy with preservation of the nipple -areolar complex.
Impact of Immediate Surgical Reconstruction Following Wide Local Excision of Malignant Head and Neck Melanoma
Authors: Hu Allison C. , Lee Seung Ah , Clark Emily G. , Yamamoto Maki , Jakowatz James G. , Evans Gregory R. D.
Published: February 2020

Background:

The role of surgical reconstruction following melanoma extirpation is well recognized. Although technical considerations depend on patient anatomy and surgeon preference, the optimal timing of reconstruction remains unclear. This study aims to evaluate clinical and oncologic outcomes in melanoma extirpation followed by immediate reconstruction.

Methods:

We retrospectively identified patients who underwent immediate reconstruction following head and neck melanoma excision at our institution between January 2013 and December 2016. Demographic and clinical characteristics, operative variables, and outcome data were extracted.

Results:

Overall, 197 patients (male 70.6%) underwent excision followed by immediate reconstruction. Of the 70 patients with a history of cutaneous malignancy, 46 (65.7%) had a prior melanoma and 26 (37.1%) had 2 or more types of skin cancers. Of the 202 lesions resected, 138 (68.3%) were invasive, whereas 64 (31.7%) were in situ. The most frequent anatomic location involved was the cheek (34.2%), followed by scalp (31.2%). Reconstruction technique varied, with 116 (57.4%) lesions repaired by adjacent tissue transfer, 24 (11.9%) by full-thickness skin graft, 23 (11.4%) by complex primary closure, 17 (8.4%) by split-thickness skin graft, and 22 (10.9%) by more than 1 technique. On postoperative pathologic assessment, 2 patients had positive margins and 5 experienced local recurrence (mean follow-up: 2.3 years). In an unadjusted bivariate analysis, history of melanoma (P = 0.015) was significantly associated with local recurrence.

Conclusions:

Reconstruction at time of excision is an oncologically safe approach for the management of patients with malignant melanoma. A prior history of melanoma may be associated with local recurrence.
The brave new world of genetic testing in the management of the dyslipidaemias
Authors: Nawawi Hapizah Md , Chua Yung-An , Watts Gerald F.
Published: February 2020

Purpose of review

With the exception of familial hypercholesterolaemia, the value of genetic testing for managing dyslipidaemias is not established. We review the genetics of major dyslipidaemias in context of clinical practice.

Recent findings

Genetic testing for familial hypercholesterolaemia is valuable to enhance diagnostic precision, cascade testing, risk prediction and the use of new medications. Hypertriglyceridaemia may be caused by rare recessive monogenic, or by polygenic, gene variants; genetic testing may be useful in the former, for which antisense therapy targeting apoC-III has been approved. Familial high-density lipoprotein deficiency is caused by specific genetic mutations, but there is no effective therapy. Familial combined hyperlipidaemia (FCHL) is caused by polygenic variants for which there is no specific gene testing panel. Familial dysbetalipoproteinaemia is less frequent and commonly caused by APOE ε2ε2 homozygosity; as with FCHL, it is responsive to lifestyle modifications and statins or/and fibrates. Elevated lipoprotein(a) is a quantitative genetic trait whose value in risk prediction over-rides genetic testing; treatment relies on RNA therapeutics.

Genetic testing is not at present commonly available for managing dyslipidaemias. Rapidly advancing technology may presage wider use, but its worth will require demonstration of cost-effectiveness and a healthcare workforce trained in genomic medicine.
Atrial fibrillation in patients with heart failure with preserved ejection fraction
Authors: Aldaas Omar M. , Malladi Chaitanya L. , Hsu Jonathan C.
Published: February 2020

Purpose of review

To review the shared pathology of atrial fibrillation and heart failure with preserved ejection fraction (HFpEF) and the prognostic, diagnostic, and treatment challenges incurred by the co-occurrence of these increasingly prevalent diseases.

Recent findings

Multiple risk factors and mechanisms have been proposed as potentially linking atrial fibrillation and HFpEF, with systemic inflammation more recently being invoked. Nonvitamin K oral anticoagulants, left atrial appendage occlusion devices, and catheter ablation have emerged as alternative treatment options. Other novel pharmacological agents, such as neprilysin inhibitors, need to be studied further in this patient population.

Atrial fibrillation and HFpEF commonly co-occur because of their shared risk factors and pathophysiology and incur increased morbidity and mortality relative to either condition alone. Although the presence of both diseases can often make each diagnosis difficult, it is important to do so early in the disease course as there are now a variety of treatment options aimed at improving symptoms and quality of life, slowing disease progression, and improving prognosis. However, more research needs to be performed on the role of catheter ablation in this population. Novel pharmacologic and procedural treatment options appear promising and may further improve the treatment options available to this growing population.
Treating Uncomfortable Contact Lens Wear With Orthokeratology
Authors: Duong Kim , McGwin Gerald , Franklin Quentin X. , Cox Jared , Pucker Andrew D.
Published: February 2020

Objectives:

Many contact lens (CL) users permanently discontinue wear because of ocular dryness and discomfort. This study aimed to determine whether refitting symptomatic soft CL wearers in to orthokeratology could improve ocular symptoms and signs.

Methods:

This was a prospective, 3-month, open-label study of symptomatic (Contact Lens Dry Eye Questionnaire [CLDEQ-8] ≥12) soft CL wearers who were between the ages of 18 and 45 years. All subjects were refit into orthokeratology CLs (Emerald, Euclid Systems). The following tests were completed: CL history, Standardized Patient Evaluation of Eye Dryness (SPEED) questionnaire, CLDEQ-8, CLDEQ-4, logarithm of the minimum angle of resolution visual acuity, pupil size, refractive error, slit-lamp biomicroscopy, noninvasive tear break-up time, tear meniscus height, phenol red thread, conjunctival staining, corneal aesthesiometry, and corneal topography.

Results:

Twenty-nine of 40 qualifying subjects (age=24.43±4.62 years) completed the study. No significant differences were detected between completed and noncomplete subjects. Completed subjects had significantly better CLDEQ-8, CLDEQ-4, and SPEED scores at 3 months compared with baseline. Completed subjects had significantly better conjunctival staining scores and flatter keratometry values at 1 month compared with baseline.

Conclusions:

Although not all symptomatic soft CL wearers were able to be refit into orthokeratology, subjects who were wearing orthokeratology at 3 months had a significant and clinically meaningful improvement in ocular symptoms. Additional work is needed to determine the mechanism leading to improved comfort because few clinical signs were changed after switching to orthokeratology.
The Antimicrobial Activity of Multipurpose Disinfecting Solutions in the Presence of Different Organic Soils
Authors: Yamasaki Katsuhide , Mizuno Yohei , Kitamura Yoshiyuki , Willcox Mark
Published: February 2020

Objective:

During use, contact lens disinfecting solutions are exposed to tears and clinical microbial isolates. The current study was designed to test the performance of several disinfecting solution in the presence of organic soils or clinical isolates.

Methods:

Standard and clinical isolates were exposed to the disinfecting solutions in the presence or absence of different organic soils. The number of microbial cells killed during disinfection was established by growing cells after disinfection on agar plates.

Results:

The disinfecting activity of the povidone-iodine or hydrogen peroxide solutions was not affected by the organic soils or clinical isolates. The presence of yeast organic soil did not affect the performance of the disinfecting solutions when tested with standard microbial strains, but the addition of a model tear organic soil significantly reduced the disinfecting activity of the solutions containing various combinations of polyhexamethylene biguanide, polyquaternium-1, alexidine, and myristamindopropyl dimethylamine especially when tested against the standard fungal strains (reducing the effectiveness by between 0.5–4 log10) or the clinical bacterial isolates (reducing the effectiveness by between 0.5–3.5 log10). One disinfecting solution that contained polyquaternium-1 and myristamindopropyl dimethylamine had very poor activity against the clinical bacterial isolates in the absence or presence of either organic soil.

Conclusions:

Povidone-iodine or hydrogen peroxide disinfecting solutions are not affected by organic soils and are very active against clinical bacterial isolates. Disinfecting solutions containing combinations of polyhexamethylene biguanide, polyquaternium-1, alexidine, and myristamindopropyl dimethylamine are affected by model tear organic soil and may have poor activity against clinical isolates.
Central Retinal Vessel Trunk Caliber Changes After Short-term Intraocular Pressure Elevation
Authors: Zhang Qi , Lin Cai Xia , Yang Hongli , Chen Jian Dong , Jonas Jost B. , Wang Ya Xing
Published: February 2020

Precis:

After a short-term intraocular pressure (IOP) elevation, the central retinal vein caliber may be widened at lower IOP rise levels, while be compressed at higher IOP rise values.

Purpose:

The purpose of this study was to investigate changes in the calibers of the central retinal vein trunk (CRVT) and central retinal artery trunk (CRAT) trunk during a short-term elevation of IOP.

Methods:

A prospective observational study. Acute primary angle-closure suspects underwent a dark room prone provocative test (DRPPT) for 2 hours. Before and at the end of the test, tonometry, swept-source optical coherence tomography, and nonmydriatic fundus photography were performed. The calibers of the CRVT and CRAT were measured on the fundus photos taken at baseline and at the end of the DRPPT.

Results:

The study included 101 eyes (61 individuals; mean age: 54.8±9.3 y; range: 30 to 70 y) which showed an increase in IOP by 9.6±9.0 mm Hg (range: 2.3 to 46.7 mm Hg). From baseline to the end of the DRPPT, the mean CRVT caliber increased from 101.8±25.9 to 107.7±26.6 μm (P<0.001), while the CRAT caliber did not differ significantly (110.3±24.2 vs. 109.7±21.5 μm; P=0.54) during the test. The CRVT widening was larger in the subgroup with IOP rise of <6 mm Hg than in the subgroup with an IOP rise of 6 to 15 mm Hg, while in the subgroup with an IOP rise of >15 mm Hg the CRVT caliber did not change significantly (P=0.20) during the test.

Conclusions:

A physiological short-term IOP rise at lower levels of IOP elevation led to a widening of the CRVT, while at higher IOP values, the further IOP-rise may have compressed the retinal vein. Because of higher intraluminal pressure values, the retinal artery diameters were not affected by the IOP-rise.
Pericardium Patch Graft (Tutoplast) for Bleb Repair and Bleb Remodelling After Nonpenetrating Filtering Surgery: 6-Month Outcomes
Authors: Niegowski Laëtitia J. , Bravetti Giorgio E. , Gillmann Kevin , Mansouri Kaweh , Mermoud André
Published: February 2020

Purpose:

The purpose of this study was to evaluate the outcome of pericardium patch graft (Tutoplast) as an adjuvant to either bleb repair or bleb reduction after nonpenetrating filtering surgery.

Methods:

Retrospective study, at a tertiary glaucoma center. Bleb revision with Tutoplast positioning was performed either for bleb repair to treat early leaks or hypotony with maculopathy, either for bleb reduction to improve ocular pain, discomfort, burning, foreign body sensation, tearing, and fluctuations of visual acuity. Intraocular pressure (IOP), best corrected visual acuity, number of antiglaucoma medications, and postoperative complications were analyzed postoperatively at 1 week, 1, 3, 6 months, and compared with the preoperative baseline. Surgical success was defined as achieving an IOP between 8 and 16 mm Hg.

Results:

Six-month data were available from 15 eyes of 15 patients; mean patient age was 69.6±11.7 (66.7% male). Bleb revision was necessary for 10 patients due to bleb dysesthesia (bleb reduction), and in 5 patients due to leaking filtering bleb (bleb repair). The success rate was 73.3% at 6 months, with a significant IOP increase from 4.9±2.2 mm Hg preoperatively to 12.7±3.5 mm Hg at 6 months (P=0.0001), and a concomitant rise of best corrected visual acuity from 0.5±0.3 to 0.6±0.3 (P=0.2871). To control IOP, antiglaucoma medications were needed for 3 patients (20%) at 6 months. Overall, 3 patients (20%) required additional bleb revision for persistent hypotony, and 1 patient underwent a subsequent glaucoma surgery (transscleral cyclodestruction).

Conclusion:

Pericardium patch graft (Tutoplast) is a safe and effective adjuvant for bleb revision due to bleb dysesthesia of leaking filtering bleb after nonpenetrating filtering surgery.
A New Technique of iPhone 11 Pro Max Smartphone-aided Angle Video and Standstill Image Documentation
Authors: Pujari Amar , Behera Aswini K. , Agarwal Divya , Sihota Ramanjit , Dada Tanuj
Published: February 2020

In this report, the authors highlight 2 effective and simple techniques of video documentation of the anterior chamber angle using the newer generation iPhone, iPhone 11 Pro Max. In these techniques, we also used a commercially available macro lens with the phone. The patient positions his/her chin on a slit-lamp biomicroscope as done during a routine slit-lamp examination. The first observer places the gonioscope over the patient’s eye and projects a thin slit beam of light of the slit-lamp biomicroscope along the superior or inferior Gonio mirror. A second observer records the anterior chamber angle findings using the macro lens clipped smartphone after bringing it closer to the eye of the patient. In the phone, the video mode is selected after opening the phone’s camera application. In the subcategory of video mode, 1× or the wide-angle mode is chosen. Under 1× mode, the magnification is further increased to 3× to document high-quality imaging findings of angle. Similarly, in the second technique, the slit (streak) light beam of the direct ophthalmoscope was used that completely circumvented the need for a slit lamp as a source of light.
Trabeculectomy With Extended Subscleral Tunnel Versus Conventional Trabeculectomy in the Management of POAG: A 1-Year Randomized-controlled Trial
Authors: Allam Riham S.H.M. , Raafat Karim A. , Abdel-Hamid Rehab M.
Published: February 2020

Precis:

This clinical trial compares a modified trabeculectomy technique [extended subscleral tunnel (ESST)] with conventional trabeculectomy [subscleral trabeculectomy (SST)] in terms of success rate and bleb morphology. ESST showed comparable results, with lower incidence of bleb-related complications and need for postoperative antiglaucoma medications.

Background:

To evaluate the outcome of modified trabeculectomy with extended subscleral tunnel “ESST” versus conventional subscleral trabeculectomy “SST” in the management of uncontrolled primary open-angle glaucoma.

Participants and Methods:

This is a randomized clinical trial of 40 eyes (40 patients) divided into 2 equal groups. In the first group, a conventional SST with adjuvant 0.3% mitomycin-C was performed. In the second group, the ESST group, an additional 1.00 mm wide longitudinal scleral groove was dissected and excised in the center of the deep scleral bed extending 1.00 mm beyond the posterior margin of the flap. Patients were examined on days 1, 7, 14, 30, 90, 180, and at 1 year, with a special focus on intraocular pressure and bleb morphology. Postoperative ultrasound biomicroscopy was performed to evaluate the surgical area.

Results:

Both groups showed a significant reduction in intraocular pressure, with the ESST group showing significantly lower values on days 7, 14, 30, 90, and 180 (P=0.001, 0.004, 0.026, 0.001, and 0.048), but no significant differences on day 1 and at 1 year (P=0.06 and 0.07). The need for postoperative antiglaucoma medications was significantly lower in the ESST group (P=0.043). Visually significant cataract and bleb related complications were more in the SST group (P=0.044 and <0.001). Significantly more eyes in the ESST group showed normal bleb vascularity and wider extent.

Conclusions:

ESST offers a guarded posterior flow with a success rate comparable to that of conventional SST. ESST could minimize bleb-related complications and bleb-dysesthesia with better long-term bleb morphology and vascularity. It could also minimize the need for further adjuvant postoperative antiglaucoma medications.
High Frequency of Aichivirus in Children With Acute Gastroenteritis in Iran
Authors: Taghinejad Mohammad , Ghaderi Mostafa , Mousavi-Nasab Seyed Dawood
Published: February 2020

Background:

Initially, detection and isolation of Aichivirus as a new member of Picornaviridae family was documented in Japan. Aichivirus species belongs to genus Kobuvirus, including 3 genotypes A, B and C. In previous studies, it has been suggested that Aichivirus infect humans by fecal-oral route. To establish an investigation for the occurrence of Aichivirus among pediatric patients involved to acute gastroenteritis, we developed a reverse transcription quantitative polymerase chain reaction assay for detection and quantification of Aichivirus in stool specimens.

Material and Methods:

In this study, a total of 160 stool samples from September 2018 to May 2019 were collected from pediatric patients presenting with acute gastroenteritis in Karaj hospital, Iran. After viral RNA extraction, the reverse transcription quantitative polymerase chain reaction was performed to amplify the 3CD junction region of Aichivirus genome and viral load was assessed. Aichivirus genomic RNA was detected in 13/160 (8.1%) of stool samples. The highest Aichivirus detection rate was in December (30.7%). The maximum viral load was determined to be 3.9 × 108 copies/g in one sample obtained from a 1-month-old patient. The co-infection of Aichivirus with salivirus and saffold virus was also assessed by reverse transcription quantitative polymerase chain reaction, among which frequent mixed infections by 2 or more viruses were identified.

Conclusions:

This is the first documentation of Aichivirus detection in stool samples that demonstrates Aichivirus has been circulating among Iranian pediatric patients.
Genetic hypothesis for the developmental origins of health and disease theory
Authors: Zhao Xinzhi
Published: February 2020

The developmental origins of health and disease theory states that environmental stresses during the early stages of life influence health and risk of developing non-communicable diseases throughout the lifespan of an individual. Developmental plasticity is thought to be a possible underlying mechanism. Here, I discuss a contrasting but complementary genetic hypothesis regarding the developmental origins of health and disease theory: crosstalk between the genomes of the parents and offspring is responsible for shaping and adapting responses to environmental stresses, regulating early growth and predisposition to non-communicable diseases. Genetic variants that are beneficial in terms of responses to early life stresses may have pleiotropic detrimental effects on health later in life, which may change the allele frequencies driven by selection on a population level. Genetic studies on the cohort of children born after assisted reproduction could provide insight regarding the genetic mechanisms of the developmental origins of health and disease theory.
Mutation profiles of classic myeloproliferative neoplasms detected by a customized next-generation sequencing-based 50-gene panel
Authors: Huang Xiu , Wu Jiawei , Deng Xuan , Xu Xiao , Zhang Xinju , Ma Weizhe , Hu Tingting , Yang Jianmin , Guan Ming , Tang Gusheng
Published: February 2020

Objective:

A sequencing panel consisting of 50 genes was customized to reveal the potential molecular land-scapes of essential thrombocytosis, polycythemia vera, and primary myelofibrosis in Chinese patients with myeloproliferative neoplasm (MPN).

Methods:

Sixty-five MPN patients (38 with essential thrombocytosis, 21 with polycythemia vera, and 6 with primary myelofibrosis), including 12 triple-negative patients, were recruited and were screened for their mutational spectrum using next-generation sequencing technology in this retrospective observational study. This study was approved by the Institutional Review Board of Changhai Hospital, Naval Military Medical University, China.

Results:

In addition to the typical driver mutations in
JAK2
,
CALR
, and
MPL
, pathogenic mutations in 15 other genes were frequently detected among the 65 patients with MPN. The 15 mutated genes were
TET2, EZH2, ASXL1, MIR662, MLH1, MLH3, SF3B1, MSH6, BARD1, DNMT3A, KIT, MSH2, RUNX1, TP53
, and
NRAS
in this order according to the mutational frequency detected. The average number of mutated genes was 1.2 genes per patient, while in the 12 triple-negative patients with MPN (ie, patients that lack the
JAK2
,
CALR
, or
MPL
mutations), at least one of the 15 pathogenic mutations was detected for each patient. Interestingly, 4 single nucleotide polymorphisms (rs4858647, rs9376092, rs58270997, rs621940) that might be correlated to individual susceptibility to myeloproliferative neoplasm were identified among the 65 patients. We also found that single nucleotide polymorphism and/or single nucleotide variation mutations occurred in multiple loci of mismatch repair-related genes, which might contribute to the development of MPN.

Conclusion:

Our study confirms the importance of the previously known MPN relative genes and, more importantly, provides some new and potentially valuable information about mutations associated with MPNs.
Public Health Surveillance for the Prevention of Pesticide-Related Illness in Illinois
Authors: Kyeremateng-Amoah Emmanuel , Friedman Lee , Wahl Michael , Forst Linda
Published: February 2020

Objectives:

There is no pesticide related illness (PRI) surveillance program in Illinois. This study examines the quality of state-based data sources for their ability to inform public health surveillance on PRI.

Methods:

We estimated the counts of PRI by probabilistic data linkage of hospital discharge, emergency department, and poison center databases from 2010 to 2015. We characterized identified PRI cases.

Results:

We identified 3867 unique cases of PRI and 6269 asymptomatic pesticide exposures. Out of the 3867 PRI cases, there were 1319 emergency department visits and 321 hospitalizations. We identified 13 deaths and 1640 major or moderate effects from PRI. Over half of ingestion related exposures occurred in children aged 0 to 4 years. Workers’ compensation and Emergency Medical Service data were unusable.

Conclusion:

An effective public health surveillance on PRI requires reliable state data sources and cost-effective methods of assembling data from multiple sources.