bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exposure to antithyroid drugs and ethylenethiourea and risk of thyroid cancer: a systematic review of the epidemiologic evidence
Authors: La Vecchia Carlo , Turati Federica , Negri Eva 
Published: January 2021

Introduction
The thyroid peroxidase inhibiting compounds methimazole, methylthiouracil, propylthiouracil, thiouracil (i.e. ‘antithyroid’ drugs) and ethylenethiourea have been associated to thyroid tumours in rodents. According to a systematic review by the International Agency for Research on Cancer (IARC) published in 2000, evidence for the human carcinogenicity was inadequate.

Methods
We performed an up-to-date systematic review of human epidemiological studies on the association between such compounds and thyroid cancer incidence or mortality.

Results
The literature research (1999–March 2020) identified four relevant articles. Considering also reports from the previous IARC review, this systematic review considered seven reports (five distinct studies) on antithyroid drugs and two on ethylenethiourea. As for antithyroid drugs, three reports based on different follow-ups gave results from a cohort of patients treated for hyperthyroidism in 1946–1964. In the earlier report, thyroid cancer incidence was higher in patients primarily treated with antithyroid drugs (3.2/1000) than in those originally treated with thyroidectomy (0.34/1000) or radioactive iodine (0.88/1000), which can be explained by the higher frequency of subsequent thyroidectomy, and hence the higher chance of cancer detection, in that group (30 vs. 0.5 and 1.2%). The two subsequent reports found no deaths from thyroid cancer among patients treated exclusively with antithyroid drugs through 1990 and 2014. A nested case-control study found an odds ratio (OR) of thyroid cancer of 2.79 [95% confidence interval (CI), 0.78–10.02, from a 2-year lag analysis] for ≥3 vs. no propylthiouracil prescriptions. The increased risk can be attributed to advanced diagnosis of an underlying cancer, as suggested by the stronger association observed in a no-lag analysis (OR, 8.03). In a historical cohort of newly diagnosed hyperthyroid patients, the hazard ratio for treatment with radioactive iodine vs. thionamides only was 0.45 (95% CI, 0.21–0.99), possibly due to the closer surveillance of patients receiving thionamides only. Two case-control studies did not find any association with the use of antithyroid drugs. As for ethylenethiourea, no thyroid cancer cases were found in a historical cohort of 1929 workers occupationally exposed in a 15-year period and no association with proxies of mancozeb exposure (a fungicide whose main metabolite is ethylenethiourea) was detected in a cohort of >236 000 farmers.

Conclusion
There is no evidence for a relevant role of either antithyroid drugs or ethylenethiourea on thyroid cancer.
Diagnostic and prognostic value of heat shock protein 90α in malignant melanoma
Authors: Zhang Tengteng , Li Qianqian , Zhang Yiyin , Wang Qianling , Wang Hui , Gu Kangsheng 
Published: January 2021

Malignant melanoma is one of the most common tumours of the skin. Heat shock protein 90α (HSP90α) has been applied in the auxiliary diagnosis of various malignancies, as a tumour marker. This study aims to evaluate diagnostic, therapeutic efficacy and prognostic value of plasma HSP90α levels in malignant melanoma. In this study, higher plasma HSP90α levels and abnormal rates were found in malignant melanoma patients than in healthy controls (92.63 vs. 51.84 ng/mL; P
< 0.001 and 68.30 vs. 8.30%; P < 0.001). Plasma HSP90α levels were higher with Breslow thickness >4 mm, a high Clark level (IV + V), abnormal serum lactate dehydrogenase (LDH), distant metastases occurrence and Ki-67≥30% (P < 0.05). The area under the curves (AUCs) of HSP90α was greater than LDH in the training (0.847 vs. 0.677) and validation (0.867 vs. 0.672) cohort. Meanwhile, the sensitivity (76.70%) and negative predictive values (78.80%) of HSP90α were higher. Plasma HSP90α levels were significantly reduced in objective response (81.05 vs. 37.26 ng/mL; P = 0.012) and disease control patients (84.16 vs. 47.05 ng/mL; P = 0.002) post-treatment. Patients with normal HSP90α levels had slightly longer progression-free survival (PFS) than those with abnormal levels (8.0 vs. 3.5 months; P = 0.096). Unfortunately, the trend was not statistically significant. In multivariable analysis, immunotherapy was an independent prognostic factor for PFS. Nevertheless, patients with normal HSP90α levels who received chemotherapy(±targeted therapy) without immunotherapy had significantly longer PFS than patients with abnormal levels (6.0 vs. 2.0 months; P = 0.008). Therefore, HSP90α can be used for auxiliary diagnosis and predict the responses to therapy in malignant melanoma patients.
EVALUATION OF THE EFFICACY OF POSTERIOR SCLERAL CONTRACTION IN THE TREATMENT OF MACULAR HOLE WITH RETINAL DETACHMENT IN HIGH MYOPIA
Authors: Ye Jie , Wu Yue , Zhu Shuangqian , Dong Liang , Qu Jia , Lu Fan , Xue Anquan 
Published: January 2021

Purpose:
To evaluate efficacy of posterior scleral contraction for macular hole with retinal detachment in high myopia.

Methods:
Seventy-three macular hole with retinal detachment eyes were treated with posterior scleral contraction. A strip was sent across inferior–temporal scleral surface to posterior pole, then two ends were led out from nasal-inferior to temporal-superior areas. It was tightened to contract posterior sclera with designed axial length shortening ([10% of preoperative axial length-0.5] mm) after aqueous humor was drained from anterior chamber. Recovery was classified as type I (retinal reattachment with MH bridged) and II (retinal reattachment without MH bridged). Follow-up duration was 25.3 ± 18.0 months.

Results:
Axial length was 30.01 ± 2.27 mm at preoperation and shortened by 2.57 ± 0.82 mm intraoperatively. At final postoperation, maintained axial length shortening was 1.87 ± 0.92 mm. Forty-six eyes (63.0%) recovered as type I, 26 eyes (35.6%) as type II, and 1 eye (1.4%) unrecovered. Postoperative best-corrected visual acuity (logarithm of minimal angle of resolution) was better than preoperative one (0.85 ± 0.50 [Snellen 20/125] vs. 1.11 ± 0.56 [Snellen 20/250], P < 0.001) with correlation (r = 0.662, P < 0.001) and consistency (Kappa = 0.34, P < 0.001) between two. Best-corrected visual acuity improvement did not differ between recovery types (P = 0.206).

Conclusion:
Macular hole with retinal detachment was successfully recovered by posterior scleral contraction with axial length shortening. Visual improvement was achieved, correlated, and consistent with preoperative best-corrected visual acuity while independent of recovery types.
OUTER RETINAL TUBULATION MAY RESULT FROM FIBROSED TYPE 2 NEOVASCULARIZATION
Authors: Janse van Rensburg Ernst , Ryu Christina L. , Rampakakis Emmanouil , Vila Natalia , Chan Errol W. , Chen John C. 
Published: January 2021

Purpose:
To investigate the role of Type 2 macular neovascularization with subsequent subretinal fibrosis in the pathogenesis of outer retinal tubulation (ORT).

Methods:
We conducted a retrospective cohort study of patients with stabilized inactive exudative macular degeneration who had been treated with intravitreal injections of antivascular endothelial growth factor agents. Baseline fluorescein and optical coherence tomography images were included. Macular neovascularizations (MNVs) were classified by type and size. Consecutive optical coherence tomography images analyzed for ORT development.

Results:
One hundred forty-four eyes of 134 patients were included in this study. Sixty eyes presented with pure Type 1 MNV. Eighty-four eyes presented with some Type 2 component of MNV. In total, evidence of ORT is shown in 55 (38%) eyes. In the Type 1 group, 6.7% developed ORT. Outer retinal tubulation developed in 61% of eyes with some Type 2 component of the MNV. Among eyes that developed ORT, 92.7% presented with some Type 2 component. In a multivariate analysis, Type 2 membranes on optical coherence tomography (22.2 [6.1–80.8]; P < 0.001), larger MNV size {>1 DA (5.1 [1.1–24.2]; P = 0.041) and >1.5 DA (9.0 [1.8–44.0]; P = 0.007)}, and presence of subretinal fibrovascular material (3.1 [1.1—8.5]; P = < 0.03) are associated with higher odds of ORT formation. Once the ORT is formed, fibrosis was observed directly underlying the ORT on SD-optical coherence tomography in 70.9% of cases.

Conclusion:
Type 2 membranes at presentation predict ORT formation. Fibrosis often underlies ORT. This suggests that contraction of Type 2 MNV-derived fibrosis may be important in ORT formation.
Incidence and complications of retained lens fragment in the anterior chamber after uneventful cataract surgery in a United Kingdom tertiary center
Authors: Matarazzo Francesco , Phylactou Maria , Aiello Francesco , Gallo Afflitto Gabriele , Yue Sim Sing , Maurino Vincenzo 
Published: January 2021

Purpose:
To analyze the outcomes of retained lens fragment (RLF) in the anterior chamber after uneventful cataract surgery.

Setting:
Moorfields Eye Hospital, NHS Foundation Trust, London, United Kingdom.

Design:
Retrospective, observational cross-sectional study.

Methods:
A single-center, retrospective review was performed to identify patients who underwent RLF removal after uneventful phacoemulsification surgery between October 2012 and November 2018; 122 eyes from 121 patients were identified. Patient characteristics, clinical findings, visual outcomes, and need for subsequent surgical procedure were recorded. Main outcomes were change in corrected distance visual acuity (CDVA), and number and risk factors associated with additional surgery following RLF removal.

Results:
One hundred twenty-two RLF over a total of 98 467 uneventful phacoemulsification surgeries were identified, with an incidence of 1 (0.124%) in 807 operations. The mean CDVA improved significantly after RLF removal from 0.32 to 0.26 logMAR (SD 0.26) (P = .001). Six eyes (4.9%) had persistent corneal edema that required endothelial keratoplasty (EK) after a mean of 13 months after RLF removal (SD 12 months; median 8; range 4 to 35). Risk factors for EK include α-receptor blocker use (odds ratio [OR], 6.75; 95% CI, 1.069, 42.63), increased interval (month) between cataract surgery and diagnosis of RLF (OR, 1.29; CI: 1.080, 1.541), increased interval between cataract surgery and RLF washout (OR, 1.28; CI, 1.075, 1.522), and RLF diagnosis on gonioscopy (OR, 10.60; CI, 1.885, 59.59).

Conclusions:
RLF is a rare complication of uneventful cataract surgery and appears more frequently in challenging cataract cases and myopic eyes. CDVA improved significantly after RLF removal, but approximately 1 in 20 eyes needed additional surgery–mainly EK for corneal decompensation.
Outcomes of manual small incision cataract surgery and phacoemulsification in eyes with chorioretinal coloboma
Authors: Shekhar Madhu , Pai Aruna , kumar Avitesh , R Sankaranathan , Prasad R Senthil , H S Bhanumathi , Wijesinghe Hiruni Kaushalya , Mishra Chitaranjan 
Published: January 2021

Purpose:
To evaluate outcomes of manual small-incision cataract surgery (MSICS) and phacoemulsification in eyes with chorioretinal coloboma.

Setting:
Tertiary eye center, South India.

Design:
Retrospective study.

Methods:
Electronic medical records of 71 patients with chorioretinal coloboma undergoing cataract surgery from January 2017 to December 2019 were evaluated. Demographics, corrected distance visual acuity (CDVA), slitlamp biomicroscopy findings, grade of cataract, type of coloboma and associated posterior segment pathology, outcomes of different surgical techniques and risk factors for poor visual outcomes, and intraoperative complications were analyzed.

Results:
Among the 78 eyes studied, 53.9% eyes achieved visual outcome of 20/40 or greater and 20.5% eyes achieved CDVA less than 20/200. For the MSICS group, the median preoperative CDVA was 1.78 (interquartile range [IQR] 1.08 to 2.60) logMAR), which improved to 0.60 (IQR 0.30-1.08) logMAR postoperatively. In phacoemulsification group, the CDVA improved from 0.78 (IQR 0.60-1.00) logMAR to 0.18 (IQR 0.18-0.30) logMAR. Statistically significant visual improvement was noticed in both groups (P < .001 in both). However, eyes that underwent phacoemulsification showed better visual recovery (P < .001). The mean age at presentation was 49.7 ± 10.8 years. MSICS was the most commonly performed surgery (61.54%), and 62 eyes had uneventful cataract surgery. Twelve eyes in MSICS group and 4 eyes in phacoemulsification group had intraoperative complications. Poor visual outcome was associated with male sex, microcornea, hard cataracts, and macular involvement of coloboma.

Conclusions:.
MSICS is an alternative to phacoemulsification in colobomatous eyes with advanced cataract. Hard cataract and microcornea were risk factors for intraoperative complications. Significant postoperative improvement in CDVA was noticed in both macula involved and macula not involved groups.
Preloaded injectors used in a clinical study: videographic assessment and laboratory analysis of injector nozzle damage
Authors: Khoramnia Ramin , Yildirim Timur M. , Weindler Jan , Naujokaitis Tadas , Dzhambazova Mariyana , Auffarth Gerd U. 
Published: January 2021

Purpose:
To evaluate quality and duration of implantation of 2 preloaded intraocular lens (IOL) injectors and assess postimplantation damage.

Setting:
The David J. Apple Center for Vision Research, Department of Ophthalmology, University of Heidelberg, Heidelberg, Germany.

Design:
Prospective, randomized, comparative study with laboratory investigation.

Methods:
Implantation videos and postuse injectors from 60 paired eyes of 30 bilateral cataract patients were included. Patient eyes were randomly assigned for implantation with 2 different preloaded injectors: the AutonoMe with a Clareon IOL (Alcon Laboratories, Inc.) and the iSert with a Vivinex IOL (Hoya Corp.). Videos were reviewed for events during the implantation procedure, and the duration of each step of implantation. Injector nozzles were examined under light and scanning electron microscopy. Damage was graded and correlated with the IOL power. Three months postoperatively IOLs were assessed for material changes.

Results:
IOL delivery was without any critical events in 60 of the 60 eyes. The implantation took 56 seconds with the AutonoMe and 44 seconds with the iSert (P < .05). Most AutonoMe injectors (29; 97%) showed no damage or slight deformation. In most of the iSert injectors (25; 80%), short or extended cracks were present, and damage lengths correlated with the IOL power. All IOLs were free of material changes, including glistenings, 3 months postoperatively.

Conclusions:
Both preloaded IOL injectors allowed a safe and convenient IOL delivery. Implantation of the Clareon IOL took, on average, slightly longer than that of the Vivinex IOL, mostly due to a slower IOL unfolding. The AutonoMe showed less nozzle tip damage than that of the iSert.
Comparative evaluation of once-daily and twice-daily dosing of topical bromfenac 0.09%: aqueous pharmacokinetics and clinical efficacy study
Authors: Titiyal Jeewan S. , Thangavel Rajeswari , Kaur Manpreet , Venkatesh Pradeep , Velpandian T. , Sinha Rajesh 
Published: January 2021

Purpose:
To evaluate aqueous pharmacokinetics of topical bromfenac 0.09% and compare clinical outcomes of once- and twice-daily dosing in phacoemulsification.

Setting:
Dr. R.P. Center for Ophthalmic Sciences, AIIMS, New Delhi, India.

Design:
Prospective interventional study.

Methods:
In phase I, single-drop aqueous pharmacokinetics of topical bromfenac was estimated at 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 12 hours, and 24 hours using liquid chromatography mass spectrometry in 60 eyes. In phase II, 45 eyes undergoing phacoemulsification were enrolled: group I (control, n = 15), group II (once-daily bromfenac, n = 14), and group III (twice-daily bromfenac, n = 16). Intraoperative pupillary miosis, postoperative anterior chamber (AC) flare, Summed Ocular Inflammation Score (SOIS), central macular thickness (CMT), and pain scores were assessed. Follow-up was performed at 1 day, 7 days, 28 days, and 90 days postoperatively.

Results:
Half-life of topical bromfenac was 3.6 hours, mean residence time 5.5 hours, and peak concentration (63.73 ng/mL) achieved after 2 hours. Aqueous concentration was more than inhibitory concentration (IC50) at 12 hours but not at 24 hours. Cumulative effect was observed with repeated dosing with aqueous levels more than IC50 in once-daily and twice-daily groups at 5 days. Significant intraoperative miosis was observed in group I. Pain score, AC flare, and SOIS were significantly more in group I (P < .001) and comparable in groups II and III at all timepoints. CMT was comparable in all groups; no case developed cystoid macular edema.

Conclusions:
Single-dose topical bromfenac did not maintain therapeutic aqueous concentration over 24 hours; however, cumulative effect was observed with repeated dosing. Clinical efficacy of once-daily and twice-daily dosing was comparable.
The effects of long-term menstrual pain on pain empathy in women with primary dysmenorrhea
Authors: Mu Junya , Wang Qiming , Dun Wanghuan , Yang Jing , Wang Ke , Zhang Ming , Liu Jixin 
Published: January 2021

Abstract
Primary dysmenorrhea (PDM) is not only a painful experience but also affects the psychological and affective states of women. Neuroimaging studies have revealed shared neural substrates for somatic and empathic pains in healthy subjects. However, little is known about the relationship between pain intensity and pain empathy in pain disorders. The cyclic nature of PDM makes it a unique model for investigating this issue during a patients' pain phase. To study how long-term pain modulates empathy for pain, T1-weighted magnetic resonance imaging scans were obtained in 39 PDM patients and 41 matched female healthy controls during menstruation. Subjects viewed static visual stimuli of the limbs submitted to painful and nonpainful stimulation to solicit empathy. The visual analogue scale for pain intensity and the Interpersonal Reactivity Index for empathic ability were also obtained. We found that women with PDM exhibited higher pain empathy compared with controls. The anterior insula and brain regions related to sensory discrimination with decreased gray matter volumes were not only shared but also acted as a mediator between pain intensity and pain empathy in PDM patients. In addition, the general linear modeling analysis revealed that long-term pain experience was a more important factor to pain empathy compared with pain intensity. This indicated that long-term pain may cause maladaptive brain structural plasticity, which may further affect psychological adjustment to bring patients more vivid pain when they witness suffering and distress in others.
A proteome signature for acute incisional pain in dorsal root ganglia of mice
Authors: Pogatzki-Zahn Esther M. , Gomez-Varela David , Erdmann Gerrit , Kaschube Katharina , Segelcke Daniel , Schmidt Manuela 
Published: January 2021

Abstract
After surgery, acute pain is still managed insufficiently and may lead to short-term and long-term complications including chronic postsurgical pain and an increased prescription of opioids. Thus, identifying new targets specifically implicated in postoperative pain is of utmost importance to develop effective and nonaddictive analgesics. Here, we used an integrated and multimethod workflow to reveal unprecedented insights into proteome dynamics in dorsal root ganglia (DRG) of mice after plantar incision (INC). Based on a detailed characterization of INC-associated pain-related behavior profiles, including a novel paradigm for nonevoked pain, we performed quantitative mass-spectrometry–based proteomics in DRG 1 day after INC. Our data revealed a hitherto unknown INC-regulated protein signature in DRG with changes in distinct proteins and cellular signaling pathways. In particular, we show the differential regulation of 44 protein candidates, many of which are annotated with pathways related to immune and inflammatory responses such as MAPK/extracellular signal-regulated kinases signaling. Subsequent orthogonal assays comprised multiplex Western blotting, bioinformatic protein network analysis, and immunolabeling in independent mouse cohorts to validate (1) the INC-induced regulation of immune/inflammatory pathways and (2) the high priority candidate Annexin A1. Taken together, our results propose novel potential targets in the context of incision and, therefore, represent a highly valuable resource for further mechanistic and translational studies of postoperative pain.
Assessing outcome in postoperative pain trials: are we missing the point? A systematic review of pain-related outcome domains reported in studies early after total knee arthroplasty
Authors: Bigalke Stephan , Maeßen Timo V. , Schnabel Kathrin , Kaiser Ulrike , Segelcke Daniel , Meyer-Frießem Christine H. , Liedgens Hiltrud , Macháček Philipp A. , Zahn Peter K. , Pogatzki-Zahn Esther M. 
Published: January 2021

Abstract
The management of acute postoperative pain remains suboptimal. Systematic reviews and Cochrane analysis can assist with collating evidence about treatment efficacy, but the results are limited in part by heterogeneity of endpoints in clinical trials. In addition, the chosen endpoints may not be entirely clinically relevant. To investigate the endpoints assessed in perioperative pain trials, we performed a systematic literature review on outcome domains assessing effectiveness of acute pain interventions in trials after total knee arthroplasty. We followed the Cochrane recommendations for systematic reviews, searching PubMed, Cochrane, and Embase, resulting in the screening of 1590 potentially eligible studies. After final inclusion of 295 studies, we identified 11 outcome domains and 45 subdomains/descriptors with the domain “pain”/“pain intensity” most commonly assessed (98.3%), followed by “analgesic consumption” (88.8%) and “side effects” (75.3%). By contrast, “physical function” (53.5%), “satisfaction” (28.8%), and “psychological function” (11.9%) were given much less consideration. The combinations of outcome domains were inhomogeneous throughout the studies, regardless of the type of pain management investigated. In conclusion, we found that there was high variability in outcome domains and inhomogeneous combinations, as well as inconsistent subdomain descriptions and utilization in trials comparing for effectiveness of pain interventions after total knee arthroplasty. This points towards the need for harmonizing outcome domains, eg, by consenting on a core outcome set of domains which are relevant for both stakeholders and patients. Such a core outcome set should include at least 3 domains from 3 different health core areas such as pain intensity, physical function, and one psychological domain.