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Effects of bevacizumab on familial epistaxis caused by hereditary hemorrhagic telangiectasia

Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2021 May 7;56(5):436-441. doi: 10.3760/cma.j.cn115330-20201222-00939.

ABSTRACT

Objective: To observe the clinical effects of bevacizumab in the treatment of familial epistaxis caused by hereditary hemorrhagic telangiectasia (HHT). Methods: The data of 27 patients with familial epistaxis caused by HHT who were treated with bevacizumab intravenously from Beijing Anzhen Hospital, the First Clinical Center of Chinese People’s Liberation Army General Hospital and Binzhou Central Hospital between December 2016 and December 2019 were retrospectively analyzed. There were 14 males and 13 females, aged (55.3±11.2) years. The dose of bevacizumab was calculated according to the body weight of 5 mg/kg. The curative effect was observed one month after the first treatment. Visual analogue scale (VAS) was used to compare patients’ self-scores of systemic symptoms before and after treatment. Epistaxis severity score (ESS) was used to compare and analyze the six problems (including the frequency, duration, intensity, treatment demand, anemia and blood transfusion) of the patients before and after treatment. The changes of hemoglobin levels before and after treatment were compared. SPSS 20.0 statistical software was used to process the data. Results: Among the 27 patients at one month after the first bevacizumab treatment, 22 cases reported that the severity of epistaxis was improved significantly, and 5 cases reported that the treatment effect was not significant. The effective rate was 81.5% (22/27). The significant effect in 22 patients lasted for 5-24 months, with a median duration of 11.23 months. The VAS score of systemic symptoms decreased significantly compared with that before treatment (2.41±2.55 vs 8.19±1.47, t=9.708, P<0.01). The scores of six aspects and standardized scores of ESS were significantly decreased after treatment (epistaxis frequency: 1.78±1.22 vs 3.44±0.80, t=6.814, P<0.01; epistaxis duration: 0.85±0.91 vs 3.00±0.73, t=8.845, P<0.01; epistaxis intensity: 0.19±0.40 vs 1.00±0.00, t=10.696, P<0.01; treatment demand: 0.22 ± 0.42 vs 1.00±0.00, t=9.539, P<0.01; anemia: 0.41±0.50 vs 0.89±0.32, t=4.914, P<0.01; blood transfusion: 0.11±0.32 vs 0.41±0.50, t=3.309, P<0.01; ESS standardized score: 2.50±2.45 vs 7.60±1.30, t=9.344, P<0.01). The hemoglobin level after treatment was significantly higher than that before treatment ((105.48±24.31) g/L vs (73.07±23.71) g/L, t=6.864, P<0.01). Among the 27 patients, there were 8 cases of HHT1 (ENG gene) and 19 cases of HHT2 (ACVRL1 gene). The improvement duration of epistaxis in group HHT1 and group HHT2 was (4.76±5.12) months and (7.60±10.84) months, respectively, which was in group HHT2 longer than that of group HHT1, but there was no significant difference between the two groups (P>0.05). There was no significant difference in ESS scores between the two groups before and after treatment (P>0.05). Two female patients had amenorrhea after the first medication. All patients had no other adverse reactions and complications. Conclusion: Intravenous bevacizumab is significantly effective and safe in the treatment of familial epistaxis caused by HHT.

PMID:34010995 | DOI:10.3760/cma.j.cn115330-20201222-00939

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The impact of obstructive sleep apnea hypopnea syndrome on the perioperative and long-term outcome in patients with Stanford type A aortic dissection

Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2021 May 7;56(5):447-453. doi: 10.3760/cma.j.cn115330-20200716-00596.

ABSTRACT

Objective: To confirm the impact of obstructive sleep apnea hypopnea syndrome (OSAHS) on perioperative and long-term outcome in patients with Stanford type A aortic dissection. Methods: From June 2010 to July 2017, the clinical data of 91 patients with Stanford type A aortic dissection were analyzed. Among them, 51 patients with OSAHS were included in the study group and 40 patients without OSAHS were included in the control group. After 36 months follow-up, all-cause death was regarded as the end event. The clinical baseline data, perioperative period and 36 months survival rate of the two groups were compared. Kanplan-Meier method was used to describe the 36 month survival curve of the two groups. Cox proportional risk model was used to evaluate the risk ratio (HR) and 95%CI of 36 month survival rate. Results: The mortality rate during hospitalization was 5.9% (3 cases) in the study group and 5.0% (2 cases) in the control group, and the difference was not statistically significant (χ~2=0.03, P>0.05). The actual follow-up was (36.2±1.5) months, 88 cases were followed up and 3 cases were lost. The all cause mortality rate of 36 months was 27.5% (14/51)in the study group and 10.0%(4/40) in the control group, the difference was statistically significant (χ~2=4.30, P<0.05).By Cox proportional risk model analysis, 36 months after operation, the study group was compared with the control group after adjusting for age, male, bicuspid of aortic valve, chronic obstructive pulmonary disease, anemia, preoperative pericardial tamponade, postoperative organ dysfunction, preoperative LVEF, emergency operation, Sun’s operation, coronary artery bypass grafting, hypertension, cardiac arrhythmia, and advanced avulsion of distal aortic dissection The survival rate was lower, the difference was statistically significant (P<0.05).In addition to OSAHS, coronary artery bypass grafting and preoperative pericardial tamponade were also risk factors for the increase of 36 month mortality rate (HR=11.28,95%CI: 1.98-46.25, P=0.009; HR=9.08, 95%CI: 2.22-41.3, P=0.032). Conclusions: There was no significant difference in mortality during hospitalization in patients with Stanford A aortic dissection combined with OSAHS. The survival rate of 36 months after operation was lower than that of the control group.

PMID:34010997 | DOI:10.3760/cma.j.cn115330-20200716-00596

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A New Application of Gelatin Sponge in the Treatment of Hemifacial Spasm by Microvascular Decompression: A Technical Note

J Neurol Surg A Cent Eur Neurosurg. 2021 May 19. doi: 10.1055/s-0040-1720994. Online ahead of print.

ABSTRACT

OBJECTIVES: Microvascular decompression (MVD) for facial nerve remains the highly efficient hemifacial spasm (HFS) treatment. Nonetheless, a variety of cases have poor response to MVD. Using Teflon plus gelatin sponge in MVD seems to be a good solution. No existing study has examined the efficacy of using Teflon combined with gelatin sponge during MVD for HFS. Therefore, this study aimed to compare the efficacy of Teflon combined with gelatin sponge in HFS patients relative to that of Teflon alone.

PATIENTS AND METHODS: We retrospectively compared the follow-up results of patients treated with Teflon and gelatin sponge with those treated with Teflon alone previously. Six hundred and eighty-eight primary HFS patients undergoing surgery from January 2010 to January 2018 were retrospectively analyzed. Three hundred and forty-seven cases received simple Teflon, while 342 cases underwent Teflon combined with gelatin sponge.

RESULTS: In the Teflon plus gelatin sponge group, the incidences of facial palsy and hearing loss at 1 day, 1 year, and 2 years following surgery was significantly lower than those in the simple Teflon group. Differences in the success rates between Teflon plus gelatin sponge and the simple Teflon group were not statistically significant at 1 day, 1 year, and 2 years after surgery. The recurrence rate in the Teflon plus gelatin sponge group was significantly lower at 2 years.

CONCLUSION: For HFS patients undergoing MVD, using Teflon plus gelatin sponge can remarkably reduce the incidence of recurrence, facial palsy, and hearing loss compared with those using Teflon alone.

PMID:34010981 | DOI:10.1055/s-0040-1720994

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3D-FLAIR MRI findings in idiopathic sudden sensorineural hearing loss and the correlations with clinical features and prognosis

Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2021 May 7;56(5):424-430. doi: 10.3760/cma.j.cn115330-20200710-00574.

ABSTRACT

Objective: To explore the correlations of different appearances of labyrinthine 3D-FLAIR MRI with clinical features and prognosis in patients with idiopathic sudden sensorineural hearing loss (ISSNHL). Methods: Clinical data of patients with unilateral ISSNHL hospitalized from May 2017 to January 2019 were retrospectively analyzed. According to the results of 3D-FLAIR MRI, the patients were divided into three groups including hyperintense with absorption, hyperintense without absorption and normal. The differences and correlations among the three groups in clinical characteristics (gender, age, deafness side, duration, treatment days, dizziness/vertigo, basic diseases, vestibular function, deafness classification and typing) and prognosis were analyzed by SPSS 20.0 software. Results: Data were collected from 1 245 cases, including 739 (59.36%) with normal signal, 288 (23.13%) hyperintense without absorption, and 218 (17.51%) hyperintense with absorption. The side ratio, treatment days, dizziness/vertigo incidence, vestibular dysfunction, deafness classification and typing were different among the three groups (P<0.001). The incidence of right side was significantly higher in both the hyperintense with and without absorption groups than that in the normal. The vestibular dysfunction was more common in the hyperintense with absorption group than in the normal and hyperintense without absorption groups. It showed statistical differences in the dizziness/vertigo incidence, deafness classification, treatment days, and deafness typing compared between groups, which was the most significant in the hyperintense with absorption group, followed by the hyperintense without absorption group. There was no statistical difference in the total effective rate among the three groups (P=0.139), whereas a significant difference in the recovery rate (P<0.001). The prognosis was significantly correlated with duration, age, treatment days and dizziness/vertigo in the normal group (all P<0.001), correlated with duration and treatment days in the hyperintense with absorption group (both P<0.001), only correlated with the duration in the hyperintense without absorption group (P<0.001). Conclusion: 3D-FLAIR MRI manifestation is closely related to the clinical features and efficacy of ISSNHL. It is helpful to clarify the pathology of inner ear, which is expected to be a new imaging indicator for disease evaluation.

PMID:34010993 | DOI:10.3760/cma.j.cn115330-20200710-00574

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THE function and morphology study of eustachian tube based on sonotubometry and multi-slice spiral CT in normal subjects

Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2021 May 7;56(5):431-435. doi: 10.3760/cma.j.cn115330-20200810-00660.

ABSTRACT

Objective: In order to assess ET more comprehensively, sonotubometry (STM)combined with CT images were applied to investigate the opening features of eustachian tube (ET) in normal subjects. STM was also used as a monitor training ET opening maneuver and optimizing CT scan parameters. Methods: Following ET opening training monitored by STM, STM data of ET opening duration and maximum sound pressure from 13 healthy volunteers (10 males and 3 females, 22 to 26 years old) were acquired using maneuvers of swallowing and Valsalva in standing and supine positions. Two trials of CT scan, setting A (slice thickness 6.0 mm, manually simulated to 0.6 mm, reconstruction thickness 0.6 mm) for normal and Valsalva scans and setting B(slice thickness 0.4 mm,reconstruction thickness 0.4 mm)for Valsalva scan, were conducted in each subject. The bone area and cartilage area of ET were measured respectively in reconstructed CT images. Statistical software SPSS 19.0 was employed in data analysis. Results: The duration of ET opening and maximum sound pressure by Valsalva were longer and stronger than those by swallowing in both positions. For Valsalva maneuver, standing position resulted in longer ET opening duration compared to supine position (P<0.05). Under setting A, ET cartilage area was measured larger by Valsalva scan than by normal scan (P<0.05). By Valsalva scan, setting A captured larger ET cartilage area compared to setting B (P<0.05). CT setting B resulted in longer scan time in comparison to setting A (P<0.05). Conclusions: Techniques of STM in supine position plus CT scan under setting A can be combined by Valsalva passive ET opening. Not only the invisible ET lumen through routine CT scan can be illustrated, but also relevant ET open-close process is shown, therefore, this study provides the technique for ET research of function and structure.

PMID:34010994 | DOI:10.3760/cma.j.cn115330-20200810-00660

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Integrative genomic analysis of blood pressure and related phenotypes in rats

Dis Model Mech. 2021 May 1;14(5):dmm048090. doi: 10.1242/dmm.048090. Epub 2021 May 19.

ABSTRACT

Despite remarkable progress made in human genome-wide association studies, there remains a substantial gap between statistical evidence for genetic associations and functional comprehension of the underlying mechanisms governing these associations. As a means of bridging this gap, we performed genomic analysis of blood pressure (BP) and related phenotypes in spontaneously hypertensive rats (SHR) and their substrain, stroke-prone SHR (SHRSP), both of which are unique genetic models of severe hypertension and cardiovascular complications. By integrating whole-genome sequencing, transcriptome profiling, genome-wide linkage scans (maximum n=1415), fine congenic mapping (maximum n=8704), pharmacological intervention and comparative analysis with transcriptome-wide association study (TWAS) datasets, we searched causal genes and causal pathways for the tested traits. The overall results validated the polygenic architecture of elevated BP compared with a non-hypertensive control strain, Wistar Kyoto rats (WKY); e.g. inter-strain BP differences between SHRSP and WKY could be largely explained by an aggregate of BP changes in seven SHRSP-derived consomic strains. We identified 26 potential target genes, including rat homologs of human TWAS loci, for the tested traits. In this study, we re-discovered 18 genes that had previously been determined to contribute to hypertension or cardiovascular phenotypes. Notably, five of these genes belong to the kallikrein-kinin/renin-angiotensin systems (KKS/RAS), in which the most prominent differential expression between hypertensive and non-hypertensive alleles could be detected in rat Klk1 paralogs. In combination with a pharmacological intervention, we provide in vivo experimental evidence supporting the presence of key disease pathways, such as KKS/RAS, in a rat polygenic hypertension model.

PMID:34010951 | DOI:10.1242/dmm.048090

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Identifying Factors Affecting Outcomes in Scalp Replantation: A Systematic Review of the Literature

J Reconstr Microsurg. 2021 May 19. doi: 10.1055/s-0041-1729876. Online ahead of print.

ABSTRACT

INTRODUCTION: Replantation is the ideal treatment in traumatic scalp defects to provide immediate coverage with restoration of hair-bearing skin. However, data are limited to case reports and small case series. Comprehensive analysis of techniques and outcomes is not available. Our aim was to systematically analyze the available literature to better understand management and postoperative outcomes of patients undergoing scalp replantation.

METHODS: A systematic review of the PubMed, Cochrane, and EBSCO databases was performed in October 2019. Search terms included “replantation,” “replant,” “revascularized,” “revascularization,” “avulsion,” and “scalp.” Only papers reporting microvascular replantation of completely avulsed scalps, including case reports, were included. Review articles, non-English language articles, articles discussing nonreplant coverage, incomplete scalp avulsions, and articles discussing delayed scalp replantation were excluded. Data extracted included demographics, percent of scalp affected, mechanism, operative technique, and postoperative outcomes. Statistical analysis was performed using Mann-Whitney U tests, Kruskal-Wallis, and chi-squared tests.

RESULTS: From a total of 704 initial results, 61 studies were included for analysis comprising 149 scalps. Complete survival was achieved in 54.7%, partial survival in 38.9%, and failure in 6.7%. Total ischemia time greater than 12 hours was associated with complete replant failure. Arterial anastomoses appeared to protect against complete loss. The number of venous repairs, proportion of venous-to-arterial repairs, use of vein grafts, thromboprophylaxis, or intraoperative complications did not affect outcomes. Patients required significant volumes of blood products, which was associated with partial success. Salvage rate after unplanned return to the operating room was 60.0%. Normal hair growth was achieved in all surviving native scalp tissue.

CONCLUSION: Scalp replantations, while technically challenging, are the ideal treatment for scalp avulsions. Fortunately, these have high rates of success. And as a focal point of a patient’s appearance, this is invaluable in restoration of a sense of normalcy.

PMID:34010964 | DOI:10.1055/s-0041-1729876

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Rotational Thromboelastometry Derivative Fibrinogen-Platelet Ratio Predicts Thrombosis in Microsurgery

J Reconstr Microsurg. 2021 May 19. doi: 10.1055/s-0041-1727190. Online ahead of print.

ABSTRACT

BACKGROUND: Early detection of thrombotic events is of paramount importance for microsurgical procedures. Here, we present findings that underscore the value of rotational thromboelastometry (ROTEM) to aid in decision-making for pre- and postoperative anticoagulation, as well for patients with suspected hypercoagulability.

METHODS: We prospectively collected pre- and postoperative ROTEM values on all free flap cases at the University of California, San Francisco, from 2015 to 2016. Patient age, body mass index, comorbidities, operative reports, risk factors, thrombotic complications, and outcomes were collected from electronic medical records. Two-sample t-tests were used to compare ROTEM values between cohorts. Modeling for sensitivity, specificity, and accuracy was done for threshold fibrinogen-to-platelet ratio (FPR).

RESULTS: Of 52 patients who underwent free-tissue transfer, 15 had a thrombotic event either intraoperatively or postoperatively that required revision of the vascular anastomosis. Eight patients were clinically hypercoagulable preoperatively, seven of which had a thrombotic event. Several pre- and postoperative ROTEM values differed significantly between thrombotic and nonthrombotic cases. Preoperative (p = 0.027) and postoperative (p = 0.013) FPR were statistically significant when comparing the thrombotic to the nonthrombotic cohort. Threshold FPR ≥ 30 was the most sensitive and FPR ≥ 40 was the most specific.

CONCLUSION: Our study affirms other studies that established ROTEM as an effective predictive tool for thrombotic events during free-tissue transfer. However, a lower threshold for FPR improves catchment of thrombotic events and flap failure with acceptable sensitivity. Our results support the routine use of ROTEM for detecting hypercoagulability in patients who would potentially benefit from intervention to prevent thrombotic complications.

PMID:34010965 | DOI:10.1055/s-0041-1727190

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Longitudinal Milestone Assessment Extending Through Subspecialty Training: The Relationship Between ACGME Internal Medicine Residency Milestones and Subsequent Pulmonary and Critical Care Fellowship Milestones

Acad Med. 2021 May 18. doi: 10.1097/ACM.0000000000004165. Online ahead of print.

ABSTRACT

PURPOSE: The Accreditation Council for Graduate Medical Education (ACGME) milestones were implemented across medical subspecialties in 2015. Although milestones were proposed as a longitudinal assessment tool potentially providing opportunities for early implementation of individualized learning plans in fellowship, the association of subspecialty fellowship ratings with prior residency ratings remains unclear. This study aimed to assess the relationship between internal medicine (IM) residency milestones and pulmonary-critical care medicine (PCCM) fellowship milestones.

METHOD: A multicenter retrospective cohort analysis was conducted for all PCCM trainees enrolled in ACGME-accredited PCCM fellowship programs in 2017-2018 who had complete prior IM milestone ratings from 2014-2017. Only professionalism and interpersonal and communication skills (ICS) were included based on shared anchors between IM and PCCM milestones. Using a generalized estimating equations model, the association of PCCM milestones ≤ 2.5 during the first year of fellowship with corresponding IM subcompetencies was assessed at each time-point, nested by program. Statistical significance was determined using logistic regression.

RESULTS: The study included 354 unique PCCM fellows. For both ICS and professionalism subcompetencies, fellows with higher IM ratings were less likely to obtain PCCM ratings ≤ 2.5 during the first fellowship year. Each ICS subcompetency was significantly associated with future lapses in fellowship (ICS01: β = -0.67, P = 0.003; ICS02: β = -0.70, P = 0.001; ICS03: β = -0.60, P = 0.004) at various residency timepoints. Similar associations were noted for PROF03 (β = -0.57, P = 0.007).

CONCLUSIONS: Findings demonstrated an association between IM milestone ratings and low milestone ratings during PCCM fellowship. IM trainees with low ratings in several professionalism and ICS subcompetencies were more likely to be rated ≤ 2.5 during their first year in PCCM fellowship. This highlights a potential use of longitudinal milestones to target educational gaps at the beginning of PCCM fellowship.

PMID:34010863 | DOI:10.1097/ACM.0000000000004165

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Safety and Efficacy of Pegteograstim on Chemotherapy-induced Neutropenia in Children and Adolescents With Solid Tumors

J Pediatr Hematol Oncol. 2021 May 19. doi: 10.1097/MPH.0000000000002206. Online ahead of print.

ABSTRACT

PURPOSE: Pegteograstim (Neulapeg) is a recombinant human granulocyte colony-stimulating factor conjugated with methoxy-maleimide-polyethylene glycol. We conducted a single-arm study investigating its safety and noninferiority to conventional filgrastim in children and adolescents.

MATERIALS AND METHODS: Patients younger than 21 years with solid tumors were eligible for the study. Pegteograstim was administered on day 7 of the fourth chemotherapy cycle. Toxicities were monitored, and the change in absolute neutrophil count was compared with that of the historic control (conventional filgrastim). This trial was registered at ClinicalTrials.gov as NCT02787876.

RESULTS: Thirty-two patients were enrolled. Adverse events possibly related to pegteograstim were musculoskeletal pain (n=3), skin nodule (n=1), paroxysmal cough (n=1), urticaria (n=2), rash (n=1), and itching (n=1). These adverse events were all grade 1 or 2. Duration of neutropenia (ANC<500/µL) was shorter in the pegteograstim group compared with the historic control (median 6.5 vs. 10 d, P=0.004). The time from day 0 to neutrophil recovery (ANC>500/µL) was shorter in the pegteograstim group (median 15 vs. 18 d, P=0.003).

CONCLUSIONS: Pegteograstim is safe and shows comparable efficacy to conventional filgrastim in children and adolescents. Randomized controlled trials are needed to confirm its safety and efficacy.

PMID:34010932 | DOI:10.1097/MPH.0000000000002206