bluuebunny/crossref_metadata_2025 huggingface dataset:
A bioassay system of autologous human endothelial, smooth muscle cells, and leukocytes for use in drug discovery, phenotyping, and tissue engineering
Authors: Ahmetaj‐Shala Blerina , Kawai Ryota , Marei Isra , Nikolakopoulou Zacharoula , Shih Chih‐Chin , Konain Bhatti , Reed Daniel M. , Mongey Róisín , Kirkby Nicholas S. , Mitchell Jane A.
Published: December 2019

Blood vessels are comprised of endothelial and smooth muscle cells. Obtaining both types of cells from vessels of living donors is not possible without invasive surgery. To address this, we have devised a strategy whereby human endothelial and smooth muscle cells derived from blood progenitors from the same donor could be cultured with autologous leukocytes to generate a same donor “vessel in a dish” bioassay. Autologous sets of blood outgrowth endothelial cells (BOECs), smooth muscle cells (BO‐SMCs), and leukocytes were obtained from four donors. Cells were treated in monoculture and cumulative coculture conditions. The endothelial specific mediator endothelin‐1 along with interleukin (IL)‐6, IL‐8, tumor necrosis factor α, and interferon gamma‐induced protein 10 were measured under control culture conditions and after stimulation with cytokines. Cocultures remained viable throughout. The profile of individual mediators released from cells was consistent with what we know of endothelial and smooth muscle cells cultured from blood vessels. For the first time, we report a proof of concept study where autologous blood outgrowth “vascular” cells and leukocytes were studied alone and in coculture. This novel bioassay has usefulness in vascular biology research, patient phenotyping, drug testing, and tissue engineering.
Pain Response to Open Label Placebo in Induced Acute Pain in Healthy Adult Males
Authors: Schneider Tobias , Luethi Julian , Mauermann Eckhard , Bandschapp Oliver , Ruppen Wilhelm
Published: December 2019

Background

Open label placebos with patient education are effective in reducing chronic pain, and recent studies on their effect on pain have established interest in this field. Nevertheless, data on their effect on acute pain are scarce, and on hyperalgesia and allodynia, absent. This study assessed the effect of open label placebos on acute pain in healthy adult males and the influence of placebo education.

Methods

Thirty-two healthy males were included in this prospective, randomized, assessor-blinded crossover, single-center study assessing pain intensities (via numeric rating scale), area of hyperalgesia (von Frey filament), and allodynia (dry cotton swab) in a pain model utilizing intracutaneous electrical stimulation. The authors compared the effect of intravenous open label placebo on pain compared to no treatment. The authors further examined the effect of placebo on hyperalgesia and allodynia, and the influence of education (short vs. detailed) before placebo application. Saliva cortisol concentrations were also measured.

Results

Pain ratings (median, first to third quartile) were 21% lower during placebo treatment compared to no treatment, 4.0 (3.2 to 4.9) versus 5.1 (4.7 to 5.4), respectively (P = 0.001). The areas of hyperalgesia and allodynia were lower during placebo treatment compared to no treatment (hyperalgesia, 30 cm2 [17 to 47] vs. 55 cm2 [42 to 68], P = 0.003; allodynia, 24 cm2 [11 to 39] vs. 45 cm2 [31 to 62], P = 0.007). This corresponds to reductions of 47%. The extent of placebo education had no effect on pain. Saliva cortisol decreased significantly over time and was under the limit of detectability in the majority of participants in postbaseline measurements in both treatment branches. Baseline cortisol was not associated with the placebo effect or strength applied of current to reach defined pain ratings.

Conclusions

Open label placebos might play a role in multimodal analgesic concepts.

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New
Weight-Based Estimation of Insertion Length of the Nasogastric Tube in Extremely Low Birth-Weight Infants
Authors: Kato Yuta , Hirata Katsuya , Oshima Yukari , Wada Kazuko
Published: December 2019

Background:

Nasogastric (NG) tubes are used in the neonatal intensive care unit (NICU) for various indications. However, evidence of the best practice for estimating the NG tube insertion length in extremely low birth-weight (ELBW) infants is limited.

Purpose:

To determine a weight-based estimation formula of NG tube length in ELBW infants.

Methods:

This prospective study was performed at a single-center level III neonatal intensive care unit. Low birth-weight infants admitted between May 2009 and May 2010 who required radiography for clinical reasons were included. Radiographs of participants whose current body weights (BWs) were less than 2500 g were reviewed, and the appropriate ideal insertion length of the NG tube adjusted based on radiographs and the infant's current BW was assessed. A regression model was used to determine the ideal insertion length of the NG tube with respect to the current BW.

Results:

Overall, 533 radiographs (152 patients weighing 422-2486 g) were analyzed. Among the patients, 246 had BWs less than 1000 g and 287 had BWs more than 1000 g. Formulas that predicted NG tube length (centimeters) were derived as follows: (5 × weight [kg] + 10 [BW < 1.0 kg]) or (3 × weight [kg] + 12.5 [1.0 < BW <2.5 kg]).

Implications for Practice:

The application of the weight-based formula for estimating the NG tube length derived from the present study together with commonly used morphological methods may improve the accuracy of the NG tube insertion procedure in ELBW infants.

Implications for Research:

Further studies in other cohorts are needed.
Postpartum Readmissions Among Women With Diabetes
Authors: Mourad Mirella , Wen Timothy , Friedman Alexander M. , Lonier Jacqueline Y. , D'Alton Mary E. , Zork Noelia
Published: December 2019

OBJECTIVE:

To estimate whether women with diabetes are at risk for 60-day postpartum readmissions and associated complications.

METHODS:

The Nationwide Readmissions Database from 2010 to 2014 was analyzed to determine risk for 60-day postpartum readmissions among women with type 1 diabetes mellitus (DM), type 2 DM, gestational diabetes mellitus (GDM), and unspecified DM compared with women with no diabetes. Secondary outcomes included evaluating risk for overall severe maternal morbidity during readmissions, as well as wound complications, acute diabetic complications such as diabetic ketoacidosis, venous thromboembolism, and hypertensive diseases of pregnancy. Billing data were used to ascertain both exposures and outcomes. Adjusted log-linear regression models including demographic, hospital, medical and obstetric, and hospital factors were performed with adjusted risk ratios (aRRs) and with 95% Cis as measures of association.

RESULTS:

Of an estimated 15.7 million delivery hospitalizations, 1.1 million occurred among women with diabetes, of whom 3.2% had type 1 DM, 9.1% type 2 DM, 86.6% GDM, and 1.1% unspecified diabetes. Compared with women without diabetes (1.5% risk for readmission), risk for readmission was significantly higher for women with type 1 DM (4.4%), unspecified diabetes (4.0%), type 2 DM (3.9%), and GDM (2.0%) (P<.01). After adjusting for hospital, demographic, medical, and obstetric risk factors, type 1 DM (aRR 1.77, 95% CI 1.69–1.87), type 2 DM (aRR 1.46, 95% CI 1.42–1.51), unspecified (aRR 1.73, 95% CI 1.59–1.89) and gestational diabetes (aRR 1.16, 95% CI 1.14–1.17) retained increased risk. Among women with diabetes public insurance, lower ZIP code income quartiles, and hospitals with high safety net burdens were associated with higher risk for readmission. In both unadjusted and adjusted analyses, all diabetes diagnoses were associated with readmissions for wound complications, hypertensive diseases of pregnancy, and severe maternal morbidity.

CONCLUSION:

Although overall risk for readmission is low, pregnancies complicated by pregestational diabetes in particular are at increased risk. Women in this high-risk group should receive coordinated care and be monitored closely in the postpartum period.
Pregnancy-Associated Atypical Hemolytic Uremic Syndrome
Authors: Gupta Megha , Govindappagari Shravya , Burwick Richard M.
Published: December 2019

OBJECTIVE:

To evaluate disease presentation, diagnosis, treatment, and clinical outcomes in pregnancy-associated atypical hemolytic uremic syndrome (aHUS).

DATA SOURCES:

We searched PubMed, MEDLINE, Cochrane Library, ClinicalTrials.gov, Web of Science, EMBASE and Google Scholar, from inception until March 2018.

METHODS OF STUDY SELECTION:

We included English-language articles describing aHUS in pregnancy or postpartum. The diagnosis of aHUS was characterized by hemolysis, thrombocytopenia, and renal failure and was distinguished from typical diarrhea-associated hemolytic uremic syndrome. Patients were excluded if individual data could not be obtained, the diagnosis was unclear, or an alternative etiology was more likely, such as thrombotic thrombocytopenic purpura or Shiga toxin–producing Escherichia coli. Reports were appraised by two reviewers, with disagreements adjudicated by a third reviewer.

TABULATION, INTEGRATION, AND RESULTS:

The search identified 796 articles. After review of titles, abstracts, and full text, we identified 48 reports describing 60 unique cases of pregnancy-associated aHUS, with 66 pregnancies. Twelve cases involved pregnancy in women with known aHUS, and 54 cases involved first-episode pregnancy-associated aHUS. Women with known aHUS, particularly those with baseline creatinine at or above 1.5 mg/dL, had a high rate of adverse pregnancy outcomes. For first-episode pregnancy-associated aHUS, diagnosis most often occurred postpartum (94%), after a cesarean delivery (70%), in nulliparous women (58%). Preceding obstetric complications were common and included fetal death, preeclampsia, and hemorrhage. Diagnosis was usually made clinically, based on the triad of microangiopathic hemolysis, thrombocytopenia, and renal failure. Additional testing included renal biopsy, complement genetic testing, and ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) testing. Treatment modalities included corticosteroids, plasma exchange, dialysis, and eculizumab. More women with first-episode pregnancy-associated aHUS achieved disease remission when treated with eculizumab, compared with those not treated with eculizumab (88% vs 57%, P=.02).

CONCLUSION:

Pregnancy-associated aHUS usually presents in the postpartum period, often after a pregnancy complication, and eculizumab is effective for achieving disease remission.

SYSTEMATIC REVIEW REGISTRATION:

PROSPERO, CRD42019129266.
Interpregnancy Weight Change and Hypertension During Pregnancy
Authors: Martínez-Hortelano Jose Alberto , Cavero-Redondo Iván , Álvarez-Bueno Celia , Sanabria-Martínez Gema , Poyatos-León Raquel , Martínez-Vizcaíno Vicente
Published: December 2019

OBJECTIVE:

To synthesize evidence regarding the association between interpregnancy weight change and hypertensive disorders of pregnancy.

DATA SOURCES:

MEDLINE, EMBASE, Cochrane Library, Web of Science, and ClinicalTrials.gov databases were systematically searched from the databases’ interception until April 2019. Search strategy included the terms: “interpregnancy,” “intergestational,” “hypertension” and “hypertensive disorders.”

METHODS OF STUDY SELECTION:

Studies that assessed the relationship between interpregnancy weight change and hypertensive disorders of pregnancy were included. Twelve studies and 415,605 women were included in this systematic review and meta-analysis. We used Mendeley reference manager during the review process. Odds ratios (ORs) for the most adjusted models reported by the included articles and the corresponding 95% CIs were calculated. The no weight change category defined by each study was used as the reference category.

TABULATION, INTEGRATION, AND RESULTS:

Overall, there was an increased risk of hypertensive disorders of pregnancy associated with interpregnancy weight gain (OR 1.37; 95% CI 1.21–1.53; I2=62.1%; P<.001). Additionally, interpregnancy weight loss was associated with lower risk of developing hypertensive disorders of pregnancy (OR 0.87; 95% CI 0.75–0.99; I2=54.9%; P=.01), Finally, meta-regression showed that interpregnancy weight gain was associated with a graded increase in the risk of hypertensive disorders of pregnancy.

CONCLUSION:

This systematic review and meta-analysis provides evidence that interpregnancy weight gain is associated with an increased risk of hypertensive disorders of pregnancy, gestational hypertension, and preeclampsia.

SYSTEMATIC REVIEW REGISTRATION:

PROSPERO, CRD42018103002.
Gottesfeld-Hohler Memorial Foundation Risk Assessment for Early-Onset Preeclampsia in the United States
Authors: Copel Joshua A. , Platt Lawrence D. , Hobbins John C. , Afshar Yalda , Grechukhina Olga , Mallampati Divya , Bromley Bryann , Caughey Aaron B. , Grobman William , Han Christina S. , Nicolaides Kypros , Pettker Christian , Saade George , Sibai Baha , Simhan Hygrav , Sonek Jiri , Werner Erika , Chescheir Nancy
Published: December 2019

Preeclampsia is responsible for significant maternal and neonatal morbidity and is associated with a substantial economic burden. Aspirin has been shown to be effective in decreasing the risk of preterm preeclampsia; however, there is no consensus on the target population for aspirin prophylaxis. In May 2018, the Gottesfeld-Hohler Memorial Foundation organized a working group meeting with the goal of identifying the optimal preeclampsia risk-assessment strategy and consequent intervention in the United States. The meeting brought together experts from the leading professional societies. We discussed available literature and trends in preeclampsia risk assessment, current professional guidelines for identifying women at risk for preeclampsia, prophylactic use of aspirin in the United States and Europe, cost-effectiveness data, and feasibility of implementation of different assessment tools and preventive strategies in the United States. We identified specific knowledge gaps and future research directions in preeclampsia risk assessment and prevention that need to be addressed before practice change.
Patient-Centered Outcomes After Modified Vestibulectomy
Authors: Das Deepanjana , Davidson Emily R. W. , Walters Mark , Farrell Ruth M. , Ferrando Cecile A.
Published: December 2019

OBJECTIVE:

To describe patient outcomes after modified vestibulectomy for vulvodynia.

METHODS:

This is a mixed-methods study of patients who had undergone modified vestibulectomy for vulvodynia at a tertiary care hospital from 2009 through 2016. Demographics, preoperative and postoperative examinations, symptoms, and treatments were obtained through retrospective review. Prospective semistructured interviews were conducted from 2018 through 2019 to address patient-reported changes in pain and sexual function. Qualitative analysis was performed using a grounded theory approach.

RESULTS:

Twenty-two patients underwent modified vestibulectomy from 2009 through 2016. Age ranged from 22 to 65 years and mean body mass index was 24.3±5.4. The majority of patients were premenopausal (57%), sexually active (68%), and partnered (76%). Postoperatively, data on pain improvement were retrieved on 18 patients, of which 17 (94%) reported improvement. Patients used pelvic floor physical therapy, medications, and lubricants both preoperatively and postoperatively. For the qualitative analysis, thematic saturation was achieved with 14 interviews. Of 14 participants interviewed, 13 (93%) reported improvement with pain after surgery, 11 (79%) reported satisfaction with surgery, 8 (57%) reported satisfaction with sexual function, and 11 (79%) reported recommending the surgery to others. The following lead themes were identified: vulvodynia symptoms significantly affect quality of life; there is difficulty and delay in diagnosis owing to lack of information and awareness among patients and health care providers; and surgical success and satisfaction are influenced by patient perceptions with sexual dysfunction often persisting despite vulvar pain improvement.

CONCLUSION:

Vulvodynia patients report improvement in pain and high overall satisfaction after modified vestibulectomy, but more variable long-term effects on sexual function.
Breast Cancer Screening During Lactation
Authors: Johnson Helen M. , Lewis Tiffany C. , Mitchell Katrina B.
Published: December 2019

Breast cancer is the most common malignancy among reproductive-aged women, and an increasing number of women are breastfeeding at the time of screening initiation. The literature was reviewed to identify evidence-based guidelines for breast cancer screening during lactation. Health care providers should consider routine age-related or high-risk screening; they should also discuss alternate surveillance strategies, including deferment until cessation of breastfeeding. Shared decision-making and individualized patient care should involve consideration of the limitations of current evidence. Lactation-related radiographic changes may make examination interpretation more challenging; preprocedure milk expression and use of particular supplemental imaging modalities can improve examination sensitivity. Despite these strategies, breastfeeding women may have higher rates of false-positive findings and therefore undergo more biopsies. However, given the increased risk of biologically aggressive breast cancers in postpartum women, these risks may be outweighed by the benefits of routine breast cancer screening for breastfeeding women.
Risk of Ankle Fusion or Arthroplasty After Operatively and Nonoperatively Treated Ankle Fractures: A Matched Cohort Population Study
Authors: Axelrod Daniel , Veljkovic Andrea , Zochowski Thomas , Marks Paul , Mahomed Nizar , Wasserstein David
Published: December 2019

Objectives:

To define the risk and incidence of post-traumatic ankle arthritis requiring ankle arthroplasty or fusion after ankle fracture in a large cohort and compare that rate to matched healthy patients from the general population.

Design:

Multiple databases were used to identify patients either treated surgically or nonsurgically for ankle fractures. Each patient was matched to 4 individuals from the general population (13.5 million) with no previous treatment for ankle fracture. Ankle fusion and replacement incidence was compared using the Kaplan–Meier analysis.

Main Outcome Measurement:

Incidence of arthroplasty or fusion in all patients managed for rotational ankle fractures.

Results:

We identified 44,133 and 88,266 patients who had undergone operative management of ankle fracture (OAF) or nonoperative management of ankle fracture (NOAF) by an orthopaedic surgeon, respectively. Three hundred six (0.65%) patients who had OAF eventually underwent fusion or arthroplasty after a median 2.8 and 6.9 years, respectively. Among NOAF, n = 236 (0.17%) patients underwent fusion or arthroplasty after a median of 3.2 and 5.6 years, respectively. Surgical treatment, older age, comorbidity, and postinjury infection significantly increased the risk of fusion/arthroplasty. Compared with matched controls, the risk of fusion/arthroplasty was not independent of time, following an exponential decay pattern. OAF patient risk of fusion/arthroplasty was >20 times the general population in the 3 years after injury and approached the risk of NOAF by 14 years.

Conclusions:

Compared with a matched control group, and after adjustment for medical comorbidity, rotational ankle fractures requiring surgical open reduction internal fixation increased the likelihood of arthroplasty or fusion by 3.5 times. This study allows for accurate prognostication of patient risk of arthroplasty or fusion, using patient- and injury-specific risk factors, both immediately after the initial injury and then subsequently during the follow up.

Level of Evidence:

Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.
Hospital and Surgeon Variation in Patient-reported Functional Outcomes After Lumbar Spine Fusion
Authors: Khor Sara , Lavallee Danielle C. , Cizik Amy M. , Bellabarba Carlo , Dagal Armagan , Hart Robert A. , Howe Christopher R. , Martz R. Dean , Shonnard Neal , Flum David R.
Published: December 2019

Study Design.

Statewide retrospective cohort study using prospectively collected data from the Spine Care and Outcomes Assessment Program, capturing ∼75% of the state's spine fusion procedures.

Objective.

The aim of this study was to estimate the variation in patient-reported outcomes (PROs) 1 year after elective lumbar fusion surgery across surgeons and hospitals; and to discuss the potential impact of guiding patient selection using a PRO prediction tool.

Summary of Background Data.

Despite an increasing interest in incorporating PROs as part of the move toward value-based payment and to improve quality, limited evidence exists on how PROs vary across hospitals and surgeons, a key aspect of using these metrics for quality profiling.

Methods.

We examined patient-reported functional improvement (≥15-point reduction in the Oswestry Disability Index [ODI]) and minimal disability (reaching ≤22 on the ODI) 1 year after surgery in 17 hospitals and 58 surgeons between 2012 and 2017. Outcomes were risk-adjusted for patient characteristics with multiple logistic regressions and reliability-adjusted using hierarchical models.

Results.

Of the 737 patients who underwent lumbar fusion (mean [SD] age, 63 [12] years; 60% female; 84% had stenosis; 70% had spondylolisthesis), 58.7% achieved functional improvement and 42.5% reached minimal disability status at 1 year. After adjusting for patient factors, there was little variation between hospitals and surgeons (maximum interclass correlation was 3.5%), and this variation became statistically insignificant after further reliability adjustment. Avoiding operation on patients with <50% chance of functional improvement may reduce current surgical volume by 63%.

Conclusion.

Variations in PROs across hospitals and surgeons were mainly driven by differences in patient populations undergoing lumbar fusion, suggesting that PROs may not be useful indicators of hospital or surgeon quality. Careful patient selection using validated prediction tools may decrease differences in outcomes across hospitals and providers and improve overall quality, but would significantly reduce surgical volumes.

Level of Evidence: 3
Surgical Treatment of Patients With Dual Hip and Spinal Degenerative Disease
Authors: Yang Daniel S. , Li Neill Y. , Mariorenzi Michael C. , Kleinhenz Dominic T. , Cohen Eric M. , Daniels Alan H.
Published: December 2019

Study Design.

Retrospective study.

Objective.

To determine how lumbar spinal fusion-total hip arthroplasty (LSF-THA) operative sequence would affect THA outcomes.

Summary of Background Data.

Outcomes following THA in patients with a history of lumbar spinal degenerative disease and fusion are incompletely understood.

Methods.

The PearlDiver Research Program (www.pearldiverinc.com) was used to identify patients undergoing primary THA. Patients were divided into four cohorts: 1) Primary THA without spine pathology, 2) remote LSF prior to hip pathology and THA, and patients with concurrent hip and spinal pathology that had 3) THA following LSF, and 4) THA prior to LSF. Postoperative complications and opioid use were assessed with multivariable logistic regression to determine the effect of spinal degenerative disease and operative sequence.

Results.

Between 2007 and 2017, 85,595 patients underwent primary THA, of whom 93.6% had THA without lumbar spine degenerative disease, 0.7% had a history of remote LSF, and those with concurrent hip and spine pathology, 1.6% had THA prior to LSF, and 2.4% had THA following LSF. Patients with hip and lumbar spine pathology who underwent THA prior to LSF had significantly higher rates of dislocation (aOR = 2.46, P < 0.0001), infection (aOR = 2.65, P < 0.0001), revision surgery (aOR = 1.91, P < 0.0001), and postoperative opioid use at 1 month (aOR: 1.63, P < 0.001), 3 months (aOR = 1.80, P < 0.001), 6 months (aOR: 2.69, P < 0.001), and 12 months (aOR = 3.28, P < 0.001) compared with those treated with THA following LSF.

Conclusion.

Patients with degenerative hip and lumbar spine pathology who undergo THA prior to LSF have a significantly increased risk of postoperative dislocation, infection, revision surgery, and prolonged opioid use compared with THA after LSF. Surgeons should consider the surgical sequence of THA and LSF on outcomes for patients with this dual pathology. Shared decision making between patients, spine surgeons, and arthroplasty surgeons is necessary to optimize outcomes in patients with concomitant hip and spine pathology.

Level of Evidence: 3
3D-printed Titanium Prosthetic Reconstruction of the C2 Vertebra
Authors: Hunn Samuel A.M. , Koefman Alex J. , Hunn Andrew W.M.
Published: December 2019

Study Design.

Three patients were treated at our center with patient-specific three-dimensional (3D)-printed titanium prostheses for the reconstruction of structurally compromised C2 vertebrae.

Objective.

To describe our surgical and device design approach to these clinical scenarios and evaluate their outcomes.

Summary of Background Data.

There are a limited but increasing number of case reports and series describing the use of 3D-printed prostheses for high cervical surgery.

Methods.

We have collated and reviewed three cases using patient-specific 3D-printed prostheses.

Results.

We report two cases arising from neoplastic destruction; one resulting from metastatic medullary thyroid carcinoma, and the other from multiple myeloma. We additionally describe a case of C2 compromise as a complication of rheumatoid arthritis. All patients included in this report achieved successful surgical outcomes and symptom relief without significant complication. Clinical and radiological follow-up has demonstrated good outcomes in all cases up to 14-months postprocedure.

Conclusions.

These cases describe successful use of custom 3D-printed prostheses for reconstruction of the anterior vertebral column through C2, and add to the emerging body of literature detailing the use of custom prostheses for complex spinal surgery.

Level of Evidence: 4.
Analysis of Heterogeneity in Survival Benefit of Immunotherapy in Oncology According to Patient Demographics and Performance Status
Authors: Butaney Mohit , Satkunasivam Raj , Goldberg Hanan , Freedland Stephen J. , Patel Sandip P. , Hamid Omid , Pal Sumanta K. , Klaassen Zachary , Wallis Christopher J.D.
Published: December 2019

Objectives:

Immunotherapy (IO) has become standard of care (SOC) for many advanced malignancies, although identifying patients likely to benefit remains difficult. We sought to assess whether demographic factors are associated with response to IO, compared with SOC systemic therapy, using stratified meta-analysis.

Methods:

A systematic review of MEDLINE, PubMed, Embase, and Scopus from inception to October 2, 2018. Randomized controlled trials comparing IO to SOC in patients with advanced solid organ malignancies were included if results were stratified by age, performance status (PS), or race, assessing overall survival (OS). Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for each group using random-effects models independently.

Results:

We identified 21 eligible randomized controlled trials, including 20 stratified by age, 17 by PS, and 4 by race. Patients with PS 0 (HR, 0.74; 95% CI, 0.63-0.86) and PS≥1 (HR, 0.75; 95% CI, 0.68-0.83) had similar OS benefits from IO compared with SOC (P=0.80). There was no difference on the basis of patient race (white vs. nonwhite) (P=0.46). IO demonstrated an OS benefit for younger (below 65 y: HR, 0.73; 95% CI, 0.65-0.82) and older (65 y and above: HR, 0.79; 95% CI, 0.71-0.88) patients with no difference between age groups (P=0.27). Among prespecified subgroup analyses, there was significant effect modification in 2 subgroups: younger patients in the first-line setting (P=0.03) and those receiving anti-CTLA-4 drugs (P=0.05).

Conclusions:

When examining OS using stratified meta-analysis, we did not demonstrate significant differences in IO efficacy according to patient age, PS or race, though data on race were sparse.
Curative Intent Radiotherapy Delivered Within the Last Year of Life
Authors: Tseng Yolanda D. , Mezheritsky Irina , Halasz Lia M. , Lo Simon S. , Loggers Elizabeth T.
Published: December 2019

Objectives:

We studied a cohort of cancer patients that underwent curative-intent radiation within the last year of life (LYOL). Given the unexpectedly short survival, we evaluated the proportion with relapsed/refractory disease, determined causes of death, and explored whether treatment intent was associated with aggressiveness of care at the end of life.

Materials and Methods:

We extracted and linked claims data and radiotherapy records for patients seen at a single academic institution that died between October 1, 2014, and September 30, 2015.

Results:

Among 870 cancer patients, 290 were irradiated within the LYOL, of which 287 had treatment intent recorded (101 curative-intent, 186 palliative-intent). The majority of curative-intent patients had hematologic malignancies and/or underwent transplant (44.6%), followed by head and neck (9.9%) and gastrointestinal malignancies (9.9%). Half (n=49; 48.5%) had relapsed/refractory disease at the time of curative-intent radiation, including 13 with metastatic disease. Tumor progression (n=65; 64.4%) was the most common cause of death, followed by treatment-related mortality (n=27; 26.7%), of which transplant/hematologic malignancy patients (n=19) were the majority. Compared with palliative-intent patients, curative-intent patients had significantly higher rates of chemotherapy use within 14 days of death (P=0.04), intensive care unit stay within 30 days of death (P<0.00001), and death in the intensive care unit (P=0.001).

Conclusions:

Cancer patients that receive curative-intent radiation in the LYOL appear to be heterogeneous and receive more aggressive care at the end of life compared with palliative-intent patients. Categorizing radiation as curative in patients with metastatic disease may reflect inappropriate decision-making among physicians. Additional studies are needed to understand how radiation oncologists categorize treatment as curative and whether prognostication models may help discriminate patients undergoing curative-intent radiation that have limited life expectancies.
Vital Status Ascertainment for a Historic Diverse Cohort of U.S. Women
Authors: Pollack Anna Z. , Hinkle Stefanie N. , Liu Danping , Yeung Edwina H. , Grantz Katherine L. , Mumford Sunni L. , Perkins Neil , Sjaarda Lindsey A. , Mills James L. , Mendola Pauline , Zhang Cuilin , Schisterman Enrique F.
Published: December 2019

Background:

Studies linking large pregnancy cohorts with mortality data can address critical questions about long-term implications of gravid health, yet relevant US data are scant. We examined the feasibility of linking the Collaborative Perinatal Project, a large multiracial U.S. cohort study of pregnant women (n = 48,197; 1959–1966), to death records.

Methods:

We abstracted essential National Death Index (NDI) (1979–2016) (n = 46,428). We performed a linkage to the Social Security Administration Death Master File through 2016 (n = 46,450). Genealogists manually searched vital status in 2016 for a random sample of women (n = 1,249). We conducted agreement analyses for women with abstracted data among the three sources. As proof of concept, we calculated adjusted associations between mortality and smoking and other sociodemographic factors using Cox proportional hazards regression.

Results:

We successfully abstracted identifying information for most of the cohort (97%). National Death Index identified the greatest proportion of participants deceased (35%), followed by genealogists (31%) and Death Master File (23%). Estimates of agreement (κ [95% confidence interval]) between National Death Index and Death Master File were lower (0.52 [0.51, 0.53]) than for National Death Index and genealogist (0.66 [0.61, 0.70]). As expected, compared with nonsmokers, smoking ≥1 pack per day was associated with elevated mortality for all vital sources and was strongest for National Death Index.

Conclusions:

Linking this historic cohort with mortality records was feasible and agreed reasonably on vital status when compared with other data sources. Such linkage enables future examination of pregnancy conditions in relation to mortality in a diverse U.S. cohort.
Corneal Injury Detection Using Apple iOS-Based Application Technology
Authors: Hakimi Amir A. , Heidari Andrew E.
Published: December 2019

Purpose:

To describe the feasibility of an attachment-free iOS-based cobalt blue light application to accurately detect corneal injury.

Methods:

Corneal epithelium from New Zealand White rabbits was removed by gentle scraping with a dulled scalpel or by using a classic biopsy punch (2 mm in diameter). Each cornea was then examined using a smartphone-enabled blue light after applying a fluorescein sodium ophthalmic strip. Photographs of each cornea before and after using the smartphone-based light were captured with a second smartphone device.

Results:

The iOS-based (Apple Inc., Cuptertino, CA) cobalt blue light effectively illuminated fluorescein dye in all ex vivo samples. Both circular punch biopsy and linear scalpel-induced corneal injuries were readily identified.

Conclusions:

The iOS-based cobalt blue light is a portable, low-cost, and effective alternative to commercially available cobalt blue lights.
Surgical Intervention of Periocular Infantile Hemangiomas in the Era of β-Blockers
Authors: Men Clara J. , Ediriwickrema Lilangi S. , Paik Ji Sun , Murdock Jennifer , Yen Michael T. , Ng John D. , Liu Catherine Y. , Korn Bobby S. , Kikkawa Don O.
Published: December 2019

For patients with periocular infantile hemangiomas with residual soft tissue deformity following propranolol therapy, surgical treatment plays an important role in improving functional and cosmetic outcomes with minimal side effects.

Purpose:

To examine the role of adjuvant surgical resection of infantile hemangiomas after systemic β-blocker therapy.

Methods:

This is a multicentered retrospective study. Standard protocol for oral propranolol was employed by the referring physicians. Ocular indications for surgery included ptosis obstructing the visual axis, high degrees of astigmatism causing amblyopia, or disfigurement from residual tumor. Patients underwent complete excision or debulking.

Results:

Eleven girls and 4 boys were surgically treated with mean operative age of 34.4 months. Patients were followed for a mean of 19.6 months after surgery. Four patients required surgical treatment due to an inability to tolerate medical therapy secondary to drug-related side effects (including bradycardia). The other 11 patients proceeded to surgery due to residual eyelid and orbital lesions despite medical treatment. All 15 patients underwent orbitotomy for residual hemangioma excision. Four patients also underwent simultaneous levator advancement at the time of excision. In all cases, there was resolution of ptosis with clearing of the visual axis. No complications were incurred during the surgical treatment and there were no hemangioma recurrences.

Conclusions:

This is the first study to report surgical management of periocular infantile hemangiomas recalcitrant to standard therapy in the β-blocker era. In patients with infantile hemangioma who have failed medical therapy, adjuvant surgical treatment still plays an important role. For patients with persistent tumor causing ocular sequelae, surgical intervention aimed at soft tissue debulking and ptosis repair can be successful in achieving excellent functional and aesthetic outcomes with minimal side effects.
Predictability of the Phenylephrine Test With Regard to Eyelid Skin Appearance in Patients Who Undergo Müller Muscle–Conjunctival Resection Without Blepharoplasty
Authors: Hauck Matthew J. , Steele Eric A. , Perry C. Blake
Published: December 2019

Purpose:

To evaluate the ability of preoperative phenylephrine testing to predict postoperative upper eyelid tarsal platform show in patients undergoing Müller muscle–conjunctival resection (MMCR) ptosis repair without concurrent blepharoplasty.

Methods:

A retrospective chart review was performed on 52 eyelids of patients who underwent MMCR without external skin incision. Photographs were reviewed to objectively and subjectively compare the results of phenylephrine testing to postoperative appearance. Only patients who underwent successful MMCR were included in the study. The authors defined successful MMCR as having a resulting marginal reflex distance within 1 mm of that predicted by phenylephrine testing. For objective analysis, the tarsal platform show was measured using computer software. For subjective analysis, 2 experienced examiners were asked to grade the correlation in appearance on a scale of 1–5 (1 being poor correlation and 5 being excellent correlation).

Results:

The mean tarsal platform show in the phenylephrine test photographs and the postoperative photographs was 3.8 and 3.63 mm, respectively (mean = 0.17; standard deviation = 0.71). The difference between the means was not statistically significant (p > 0.05). The mean difference in tarsal platform show between phenylephrine testing and postoperative was 0.17 mm (standard deviation = 0.71). The difference was not statistically significant (t[51] = 0.09; p > 0.05; 2 tailed). The mean subjective correlation score comparing phenylephrine testing photographs to postoperative photographs was 4.4 out of possible 5.

Conclusions:

Phenylephrine testing exhibits good predictability with regard to eyelid appearance after successful MMCR without external skin incision and, therefore, may assist the surgeon when trying to decide if blepharoplasty or eyelid crease formation is necessary at the time of MMCR.
Frontalis Linkage Without Intraoperative Eyelid Elevation for the Management of Myopathic Ptosis
Authors: Diniz Stefania B. , Akaishi Patricia M. , Cruz Antonio A. V.
Published: December 2019

Purpose:

To report the effect of frontalis linkage without intraoperative eyelid elevation for the management of myopathic ptosis.

Methods:

Retrospective analysis of 21 (42 eyelids) myopathic patients with bilateral ptosis who were operated between 1999 and 2017. All patients had orbicularis weakness and poor or absent Bell’s phenomenon. Surgery consisted of using an autogenous fascia sling to link the tarsal plate to the frontalis muscle without any degree of intraoperative eyelid elevation. The main outcome measures were margin reflex distance, brow height and degree of brow excursion and degree of lagophthalmos, and exposure keratitis.

Results:

After surgery, there were significant changes (p <0.0001) in both margin reflex distance and brow position. Mean margin reflex distance increased to 1.4 mm ± 1.34 DP and with full frontalis contraction, it reached 3.0 mm ± 1.73 DP, while mean brow position decreased 1.6 mm ± 1.59 SD, p < 0.0001. Postoperative lagophthalmos was not detected in 31 (74%) eyes. In the remaining 11 eyes (26%), lagophthalmos ranged from 1.2 to 5.2 mm (mean = 1.7 mm ± 0.74 DP). Mild inferior superficial keratitis was detected in 14 eyes (33.3%) of 7 patients only 3 of which had lagophthalmos. One patient needed additional surgery to correct unilateral eyelid retraction. Overall, 81.81% of the patients were pleased with the procedure.

Conclusions:

Myopathic ptosis can be alleviated with a minimal amount of lagophthalmos by just linking the tarsal plate to the frontalis muscle without lifting the eyelid margin intraoperatively.
Does Intraoperative Ketorolac Increase Bleeding in Oculoplastic Surgery?
Authors: Chang Minwook , Gould Adam , Gur Zvi , Buhbut Ortal , Hosalkar Hetal , Liu Catherine Y. , Korn Bobby S. , Kikkawa Don O.
Published: December 2019

Purpose:

To report adverse hemorrhagic outcomes in patients who received intravenous (IV) ketorolac during oculofacial plastic surgical procedures.

Methods:

The medical records of 111 consecutive patients who underwent lacrimal or orbital surgery, between the years 2016 and 2018, performed by a single surgeon under general anesthesia were retrospectively reviewed. Patients were excluded if they had history of a bleeding coagulopathy, anticoagulant use prior to surgery, or insufficient follow up. Patients were divided into 2 groups based on whether they received intravenous ketorolac. The primary outcome measure was the occurrence of a major postoperative bleeding event, and the secondary outcome measures were the evaluation of postoperative ecchymosis graded at 1 week after surgery and the incidence of persistent ecchymosis beyond 4 weeks.

Results:

A total of 111 patients were analyzed further, including 31 patients who received intraoperative IV ketorolac and 80 control patients who did not. The demographic characteristics between the 2 groups were similar. No major bleeding events occurred in either group. And there was no statistically significant difference between the 2 groups in terms of ecchymosis grade and the incidence of development of persistent ecchymosis. Comparing the subgroups of lacrimal and orbital cases, there was also no significance difference between these groups.

Conclusions:

This study suggests that intraoperative ketorolac use does not increase the risk of postoperative bleeding complications in oculofacial procedures. This alternative to opioids may assist with pain control and lessen the narcotic burden.
Basal Cell Carcinoma of the Eyelid With Metaplastic Bone Formation
Authors: Schaffer Lauren R. , Kim Hee Joon , Grossniklaus Hans E.
Published: December 2019

Basal cell carcinoma accounts for 90% of malignant tumors of the eyelid. Basal cell carcinoma has been reported to rarely occur in conjunction with osteoma cutis or bone formation in the skin. The mechanism of this secondary osteoma cutis has yet to be explained. Herein, the authors present the case of a 68-year-old woman with a rapidly enlarging basal cell carcinoma with secondary osteoma cutis of the left lower eyelid.
The Use of Anterograde Percutaneous Transluminal Coronary Angioplasty Balloons in Congenital Nasolacrimal Duct Obstruction: A Cost-Effective Alternative to the Traditional Dacryoplasty Balloons
Authors: Bothra Nandini , Gupta Nishi , Nowak Rafal , Ali Mohammad Javed
Published: December 2019

Purpose:

To assess the efficacy of commonly available coronary angioplasty balloon catheters as a low-cost alternative to the traditional dacryoplasty catheters in select patients of congenital nasolacrimal duct obstruction.

Methods:

A prospective, interventional study was performed between July 2018 and December 2018 in children with congenital nasolacrimal duct obstruction, who underwent balloon dacryoplasty using the coronary angioplasty balloon catheters (2.75 × 10 mm, SPALNO, Cardiomac, Haryana, India). The inclusion criteria were children ≥4 years of age, and/or previously failed probing and/or previous failed intubation. Parameters documented were demographics, techniques, costs, complications, and postoperative outcomes.

Results:

Twenty-three eyes of 22 children underwent balloon dacryoplasty using coronary angioplasty balloon catheters. The mean age of the patients was 4.33 years (range 1.5–10 years). The procedure was performed in 8 patients (8 eyes, 35%) as the primary procedure. The remaining 14 patients (15 eyes, 65%) had a history of probing, of which 4 eyes had it twice earlier. All eyes underwent balloon dacryoplasty as per standard protocols. The insertion profile and trackability of the coronary catheters were good. At a mean follow up of 6.17 months (range 1.5–9 months), anatomical and functional success was obtained in 87% cases (n = 20/23). No lacrimal passage trauma or injuries were noted during the procedure. The cost of coronary balloon catheter was approximately $60.

Conclusions:

The present pilot study has shown that outcomes of balloon dacryoplasty in patients with congenital nasolacrimal duct obstruction with coronary balloon catheters is comparable to that of traditional balloons and offers significant economic advantage for developing nations.
MiR-25 exerts cardioprotective effect in a rat model of myocardial ischemia-reperfusion injury by targeting high-mobility group box 1
Authors: Liu Qifang , Song Bo , Xu Min , An Yaping , Zhao Yidong , Yue Feng
Published: December 2019

Background:

We previously confirmed the targeting of high-mobility group box 1 (HMGB1) by miR-25. This project aims to further investigate whether miR-25 improves myocardial ischemia-reperfusion injury (IRI) in vivo by targeting HMGB1.

Methods:

A rat model of myocardial IRI was established by the ligation of the left anterior descending coronary artery for 45 minutes followed by 2, 4, or 6 hours reperfusion. The expression of miR-25, HMGB1, and apoptosis-related proteins in the myocardium was determined by quantitative real-time polymerase chain reaction (PCR) and western blotting. The activities of myocardial enzymes and the release of inflammatory cytokines were evaluated by enzyme-linked immunosorbent assay. Evans blue/triphenyltetrazolium chloride double staining was performed to assess infarct size. Myocardial apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling staining.

Results:

MiR-25 expression was significantly downregulated, while HMGB1 was highly expressed at the mRNA and protein levels in myocardial tissues after induction of the IRI model. MiR-25 agomir administration suppressed the expression of HMGB1 in myocardial tissues. Furthermore, administration of both miR-25 agomir and lentivirus-mediated short hairpin RNA (shRNA) interference targeting HMGB1 sh-HMGB1 resulted in reduced serum myocardial enzyme activities, cytokine secretion, and myocardial apoptosis during myocardial IRI.

Conclusion:

MiR-25 mitigated myocardial IRI-induced damage by targeting HMGB1.
Participating in Sports After Mitral Valve Repair for Primary Mitral Regurgitation: A Retrospective Cohort Study
Authors: Blanc Adrien , Lairez Olivier , Cariou Eve , Fournier Pauline , Poenar Ana Maria , Marcheix Bertrand , Cron Christophe , Grunenwald Etienne , Porterie Jean , Labaste François , Elbaz Meyer , Galinier Michel , Carrié Didier , Lavie-Badie Yoan
Published: December 2019

Objective:

Participating in either competitive or leisure sports is restrictive after surgical mitral valve repair (MVR). In this study, we examine the impact of sports on outcomes after MVR.

Design:

Retrospective cohort study.

Setting:

Patients aged 18 to 65 years who underwent a first-time MVR for primary mitral regurgitation (MR) in a tertiary care center.

Patients:

One hundred twenty-one consecutive patients were included in the study. The exclusion criteria were as follows: other concomitant procedures, early perioperative death or repeat intervention, noncardiac death or endocarditis during follow-up, and general contraindications for normal physical activity.

Assessment of Risk Factors:

Participation in sports was quantified by the number of hours per week during the past 6 months, classified according to the Mitchell classification and assessed with the International Physical Activity Questionnaire (IPAQ) short form.

Main Outcome Measures:

The primary composite endpoint was MVR failure defined as MR grade ≥2 or mean transmitral gradient ≥8 mm Hg, signs and symptoms of heart failure, or late-onset postoperative AF (>3 months).

Results:

The mean age was 50 ± 11 years, and there were 85 (71%) men. The median follow-up was 34 months [interquartile range (IQR): 20-50]. Fifty-six (46%) patients participated in sports regularly (median of 3 h/wk; IQR: 2-5). Twenty (17%) patients reached the primary composite endpoint with no correlation with participation in sports (P = 0.537), IPAQ categories (P = 0.849), in any of the Mitchell classification subgroups and a high level of participation in sports ≥6 hours (P = 0.679).

Conclusions:

Sports seem to be unrelated to the worst outcome after MVR.