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Systematic analysis of copy number variants of uncertain significance partially overlapping with the haploinsufficient or triplosensitive genes in clinical testing

Ann Med. 2023;55(2):2276824. doi: 10.1080/07853890.2023.2276824. Epub 2023 Nov 2.

ABSTRACT

Background: Copy number variants of uncertain significance (VUS) has brought much distress for patients and great counselling challenges for clinicians. Of these, a special type of VUS (HT-VUS), harbouring one or both breakpoints within the established haploinsufficient or triplosensitive genes, were considered to be more likely to cause clinical effects compared with other types of VUS.Methods: We retrospectively evaluated the properties and clinical significance of those HT-VUS samples in clinical testing for chromosome microarray analysis (CMA).Results: A total of 7150 samples were selected for HT-VUS screening, and 75 (1.05%) subjects with 75 HT-VUS were found. The majority of these HT-VUS were heterozygous duplications and chromosome X had the most HT-VUS. The prevalence of HT-VUS was 0.90% (28/3116) for prenatal low-risk samples, 1.18% (26/2196) for prenatal high-risk samples, 1.37% (10/728) for postnatal samples and 0.99% (11/1110) for early pregnancy loss samples. However, the incidence of HT-VUS was not statistically different between different groups.Conclusions: HT-VUS (deletions or duplications) involving introns and HT-VUS (duplications) including terminal coding exons (either the first or last exons) might be clinically neutral. Our study will be helpful for both interpretation and genetic counselling in the future.

PMID:37917952 | DOI:10.1080/07853890.2023.2276824

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Representation of Women Authorship in the Top 5 Transplantation Journals in the United States

Transplantation. 2023 Nov 2. doi: 10.1097/TP.0000000000004844. Online ahead of print.

ABSTRACT

BACKGROUND: In the United States, only 13% of transplant surgeons are women. We evaluated gender distribution and trends of American authorship over the past 10 y in high-impact solid organ transplantation journals to gain insight into the current status of women authorship in transplantation.

METHODS: Original articles from 2012 to 2021 from the 5 highest-impact solid organ transplantation journals were extracted from Scopus. First and last author’s gender was predicted using Genderize.io. Data of first and last authors, article type and topic, location, citation, and funding metrics were analyzed. Chi-square, logistic regression, and trend tests were performed where appropriate. Statistical significance was set at <0.05.

RESULTS: Women’s first and last authorship increased over time among all journals. There was an increase in women first authors in the American Journal of Transplantation and in senior women authors in Liver Transplantation and Transplantation. Significant differences in gender authorship in lung, intestine, pancreas, general, and islet cell transplantation were found. Women’s last authorship was associated with 1.69 higher odds of having a woman first author when adjusting for year and journal. There was an increase in the rate of women’s first and last author collaborations over the years. Women last authors had 1.5 higher odds of being funded by the National Institutes of Health over the years.

CONCLUSIONS: Despite an increase in women transplant surgeons and physicians, the gap in women authorship in transplantation persists. Women’s last authorship was associated with higher odds of having a woman first author, pointing to the importance of mentorship for women joining the transplant academia.

PMID:37917944 | DOI:10.1097/TP.0000000000004844

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Intravenous Calcium to Decrease Blood Loss During Intrapartum Cesarean Delivery: A Randomized Controlled Trial

Obstet Gynecol. 2023 Nov 3. doi: 10.1097/AOG.0000000000005441. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate whether prophylactic administration of 1 g of intravenous calcium chloride after cord clamping reduces blood loss from uterine atony during intrapartum cesarean delivery.

METHODS: This single-center, block-randomized, placebo-controlled, double-blind superiority trial compared the effects of 1 g intravenous calcium chloride with those of saline placebo control on blood loss at cesarean delivery. Parturients at 34 or more weeks of gestation requiring intrapartum cesarean delivery after oxytocin exposure in labor were enrolled. Calcium or saline placebo was infused over 10 minutes beginning 1 minute after umbilical cord clamping in addition to standard care with oxytocin. The primary outcome was quantitative blood loss, analyzed by inverse Gaussian regression. Planned subgroup analysis excluded nonatonic bleeding, such as hysterotomy extension, arterial bleeding, and occult placenta accreta. We planned to enroll 120 patients to show a 200-mL reduction in quantitative blood loss in planned subgroup analysis, assuming up to 40% incidence of nonatonic bleeding (80% power, α<0.05).

RESULTS: From April 2022 through March 2023, 828 laboring parturients provided consent and 120 participants were enrolled. Median blood loss was 840 mL in patients allocated to calcium chloride (n=60) and 1,051 mL in patients allocated to placebo (n=60), which was not statistically different (mean reduction 211 mL, 95% CI -33 to 410). In the planned subgroup analysis (n=39 calcium and n=40 placebo), excluding cases of surgeon-documented nonatonic bleeding, calcium reduced quantitative blood loss by 356 mL (95% CI 159-515). Rates of reported side effects were similar between the two groups (38% calcium vs 42% placebo).

CONCLUSION: Prophylactic intravenous calcium chloride administered during intrapartum cesarean delivery after umbilical cord clamping did not significantly reduce blood loss in the primary analysis. However, in the planned subgroup analysis, calcium infusion significantly reduced blood loss by approximately 350 mL. These data suggest that this inexpensive and shelf-stable medication warrants future study as a novel treatment strategy to decrease postpartum hemorrhage, the leading global cause of maternal morbidity and mortality.

CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT05027048.

PMID:37917943 | DOI:10.1097/AOG.0000000000005441

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Measure of Auditory Working Memory Span Using Monosyllabic Word Recognition Test in Young Adults With Normal Hearing: A Preliminary Study

Am J Audiol. 2023 Nov 2:1-13. doi: 10.1044/2023_AJA-23-00090. Online ahead of print.

ABSTRACT

PURPOSE: Measuring working memory at hearing clinics is important. This study attempted to develop a test protocol that measures auditory working memory using a standardized monosyllabic word list in Korean Speech Audiometry (KSA).

METHOD: We included 25 young adults with normal hearing in this study. Participants conducted word recognition and word span tests concurrently using the KSA monosyllabic word lists. We designed four test conditions according to the presence or absence of background noise and word recall order: quiet-forward (QF), quiet-backward (QB), noise-forward, (NF), and noise-backward (NB). We implemented digit span tests in the Korean Wechsler Adult Intelligence Scale-IV (K-WAIS-IV) to determine the validity of the working memory outcomes.

RESULTS: Word recognition scores of QF and QB were significantly higher than those of NF and NB. The percentages of correctly recalled words and word recall span scores were highest in QF and lowest in NB. Overall, the Pearson correlation and multiple regression statistics showed that our word span test outcomes for QB and NF were highly associated with digit span scores on the K-WAIS-IV.

CONCLUSION: Our proposed test protocol showed the possibility of measuring auditory working memory and monosyllabic word recognition simultaneously by validating the results with K-WAIS-IV outcomes.

PMID:37917922 | DOI:10.1044/2023_AJA-23-00090

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Self-Reported Symptoms of Vertigo and Imbalance Are Prevalent Among Adults With Chronic Moderate-Severe Traumatic Brain Injury: A Preliminary Analysis

Am J Audiol. 2023 Nov 2:1-6. doi: 10.1044/2023_AJA-23-00100. Online ahead of print.

ABSTRACT

PURPOSE: Dizziness and imbalance are common symptoms during the acute phase of traumatic brain injury (TBI). However, there is evidence to suggest that these symptoms persist into the chronic phase of injury. Few prospective studies have examined the frequency and type of dizziness and imbalance in adults with chronic moderate-severe TBI. The aim of this preliminary analysis was to investigate the prevalence of these symptoms in adults with chronic moderate-severe TBI.

METHOD: Twenty-four adults with chronic moderate-severe TBI and a group of 19 age-, sex-, and education-matched noninjured comparison participants were recruited. Self-reported dizziness and imbalance were measured using a modified version of a standard case history form. Significant associations between group (TBI group or noninjured comparison [NC] participants) and self-reports of dizziness, imbalance, and related symptoms (endorsed “yes” or “no”) were explored.

RESULTS: The TBI group most reported lightheadedness (75%), vertigo (38%), and imbalance and/or falling (46%). The most common related symptom reported by the TBI group was headache (63%) and nausea (46%). Significant associations revealed that the TBI group responded “yes” in higher percentages than the NC group across all categories (dizziness, imbalance, and related symptoms). There were no statistically significant relationships among dizziness, imbalance, or headache symptoms within the TBI group.

CONCLUSIONS: These preliminary findings suggest that dizziness and imbalance are prevalent in adults with chronic moderate-severe TBI. Persistent vertiginous symptoms may point to an underlying vestibular impairment. However, further research is needed to characterize vestibular function in chronic moderate-severe TBI.

PMID:37917920 | DOI:10.1044/2023_AJA-23-00100

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Hyperacusis Diagnosis and Management in the United States: Clinical Audiology Practice Patterns

Am J Audiol. 2023 Nov 2:1-12. doi: 10.1044/2023_AJA-23-00118. Online ahead of print.

ABSTRACT

PURPOSE: Hyperacusis often leads to debilitating psychosocial consequences, but there is no standard protocol for its diagnosis and management in the United States. In this study, we surveyed U.S. clinical audiologists to understand their education and clinical practices surrounding the evaluation and treatment of hyperacusis.

METHOD: An online survey was distributed to clinical audiologists across the United States. Survey responses were quantified using descriptive statistics and inductive content analysis.

RESULTS: Hyperacusis definitions and clinical practice patterns varied widely across the 102 respondents. Respondents cited a lack of education and training as the primary barrier to effective audiological diagnosis and management of hyperacusis, with most respondents reporting ≤ 5 hr of hyperacusis education. Other primary barriers to effective audiological management of hyperacusis included time constraints, reimbursement, poor sensitivity and specificity of available diagnostic tools, and poor efficacy of available treatments and management strategies. Most respondents (82.5%) agreed that audiologists are the primary professionals who are responsible for implementing hyperacusis interventions. However, 63.3% of respondents reported that their clinic does not have a hyperacusis management protocol, and 80.0% routinely recommend treatment that is outside their scope of practice to implement (cognitive behavioral therapy).

CONCLUSIONS: Clinical audiologists in the United States do not receive uniform education on hyperacusis, and they report multiple barriers to its evidence-based diagnosis and management. Effective hyperacusis management necessitates a multidisciplinary approach. The information obtained via this survey will pave the way toward the refinement of interprofessional education programs and the development of systematic, evidence-based clinical protocols for hyperacusis.

SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.24431188.

PMID:37917915 | DOI:10.1044/2023_AJA-23-00118

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Correlation Between ICU Admission Time and Long-Term Mortality in Elderly Critically Ill Patients

Altern Ther Health Med. 2023 Nov 3:AT8865. Online ahead of print.

ABSTRACT

OBJECTIVE: The the intensive care unit (ICU), also known as intensive care medicine department and intensive intensive care unit, is a medical place for centralized treatment of critical diseases and continuous monitoring and treatment. To investigate the relationship between the length of intensive care unit (ICU) admission and long-term mortality in elderly critically ill patients.

METHODS: A total of 2694 critically ill ICU patients admitted to Xianning First People’s Hospital from April 2017 to April 2021 were selected. Inclusion criteria including: age ≥ 60 years; meet the diagnostic criteria for critical illness; admission to ICU ≥ 24h. According to admission time, patients were divided into 1684 patients admitted during working hours and 1010 patients admitted during non-working hours. The relationship between the admission time of ICU patients and long-term mortality was taken as the dependent variable. The evaluation was performed using the Acute Physiology and Chronic Health Status Assessment Scale (APACHE II score). Epidemiological questionnaire was used to investigate the status of time to hospital and mortality, and the independent risk factors affecting time to hospital and mortality were analyzed by univariate and multivariate analysis. SPSS 26.0 statistical software was used for analysis and processing.

RESULTS: Among 2694 critically ill patients in ICU, 1010 patients were hospitalized during non-working hours, with an admission rate of 37.49%. The acute physiology and chronic health evaluation (APACHE) II score of non-working hours was 19.91±6.62, which is significantly higher than that of working hours (18.21±6.42) (P < .05). The mortality rates of ICU patients hospitalized during non-working hours and during working hours accounted for 30.10 % and 19.71% of all patients, respectively, with statistical significance (P < .05). Comparing the mortality rates of the two groups at different time periods, there was a significant difference between the two groups (P < .05). In order to influence the independent variables of ICU mortality (non-occurrence = 0, occurrence = 1), the significant factors of univariate analysis were included in the logistic regression equation. Time of admission, combined cardiopulmonary disease, APACHE II score, nurse workload and other factors were independent risk factors for ICU mortality.

CONCLUSION: Out-of-hours admission is associated with an increased risk of death and is associated with changes in ICU organizational structure. Therefore, sending patients to ICU in time migh help improve their life.

PMID:37917912

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Effects of Glutathione Tablets on Ferroptosis Pathway and Oxidative Stress-Related Indexes in Serum of Patients Undergoing Sevoflurane Inhalation General Anesthesia and Its Clinical Significance

Altern Ther Health Med. 2023 Nov 3:AT9641. Online ahead of print.

ABSTRACT

OBJECTIVE: To explore the effect of glutathione on serum oxidative stress, inflammatory reaction, and brain injury in patients with Sevoflurane inhalation general anesthesia based on iron metabolism pathway.

METHODS: From January 2018 to January 2023, 120 patients undergoing Sevoflurane inhalation anesthesia in Xingtai Third Hospital were divided into a control group and an observation group. The control group was given routine treatment, and the observation group patients were given oral glutathione tablets 2 weeks before anesthesia based on the control group. Relevant basic data of patients were collected 3 days before operation (T0), 1 day after the operation (T1), 3 days (T2), and 7 days (T3) respectively, and the serum oxidative stress indicators of patients in each group were measured by ELISA: SOD, MDA, GSH, Hif-1α, ferroptosis related indicators: SIRT3, GPX4; related inflammatory indicators: IL-1β, TGF-β, IL-33; neuronal injury related proteins: MBP, NGF, and statistical analysis of the data.

RESULTS: There was no significant difference in general conditions and operation time between the two groups (P > .05). Compared with the control group, the observation group showed significant differences in oxidative stress indicators: SOD in the observation group at T1, SOD, and Hif-1α in the observation group at T2, and SOD, MDA, GSH and Hif-1α in the observation group at T3. 1α, there were significant differences compared with the indicators of the control group at the same time (P < .001). In terms of inflammatory factor indicators, compared with the control group, there were significant differences in IL-1β at T1, TGF-β, and IL-33 at T2, and IL-1β, TGF-β and IL-33 at T3. (P < .001). In terms of ferroptosis indicators, compared with the control group, there were significant differences in SIRT3 at T1, SIRT3, and GPX4 at T2, and SIRT3 and GPX4 at T3 (P < .001). In terms of nerve injury-related proteins, in patients, MBP levels were negatively correlated with SIRT3 (r=-0.8979, P < .0001), MBP levels were positively correlated with GPX4 (r=0.528, P < .0001), and NGF levels were positively correlated with SIRT3 (r=0.8979, P < .0001), NGF level was negatively correlated with GPX4 (r=0.528, P < .0001).

CONCLUSION: Glutathione tablets can alleviate sevoflurane-induced ferroptosis and oxidative stress by elevating GPX4 protein levels, and glutathione tablets have an ameliorative effect on brain injury in patients with sevoflurane inhalation anesthesia.

PMID:37917909

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The Application Value of Esketamine and Dexmedetomidine in Preventing Postoperative Delirium and Hyperalgesia in Elderly Patients with Thoracic Anesthesia

Altern Ther Health Med. 2023 Nov 3:AT8067. Online ahead of print.

ABSTRACT

OBJECTIVE: Our aim was to evauate the application value of esesketamine and dexmedetomidine in preventing postoperative hyperalgesia in elderly patients who received thoracic anesthesia.

METHODS: A total of 94 elderly patients who underwent thoracic anesthesia in Sanmen People’s Hospital from January 2021 to October 2022 were selected and divided into a dexmedetomidine group (n = 47) and an esketamine group (n = 47) by the random number table method. All patients were continuously received intravenous (IV) remifentanil. In the dexmedetomidine group, dexmedetomidine 0.7 μg/kg was administered IV, followed by 0.2 to 0.5 μg/kg/h to maintain anesthesia, while in the esketamine group, esketamine 0.5 mg/kg was given IV 20 min after induction of anesthesia was completed.

RESULTS: Visual analogue scale (VAS) scores in the esketamine group were lower than in the dexmedetomidine group at 1, 6, 12 and 24 h postoperatively (P < .05), and Ramsay sedation scores were not statistically different from those in the dexmedetomidine group (P > .05). At 3 d postoperatively, the Mini-Mental State Examination (MMSE) scores in the dexmedetomidine group were lower than 1 d preoperatively; at 5 d postoperatively, the negative mood and Pittsburgh Sleep Quality Index (PSQI) scores were significantly higher in both groups than 1 d preoperatively; at 14 d postoperatively, the PSQI scores were higher in both groups than 1 d preoperatively, and there was no statistical difference between the negative mood scores at 1 d before surgery (P > .05). At 5 d postoperatively in the esketamine group, the negative mood scores were lower than in the dexmedetomidine group at 5 d postoperatively and the PSQI scores at 5 and 14 d postoperatively were lower than in the dexmedetomidine group (P < .05).

CONCLUSION: Both esketamine and dexmedetomidine can be used to prevent postoperative delirium and nociceptive hypersensitivity after anesthesia in elderly patients with thoracic surgery. However, esketamine is superior to dexmedetomidine in analgesic effect, improvement of negative mood and sleep and stabilization of intraoperative hemodynamics, leading to better effect in preventing delirium and hyperalgesia after anesthesia.

PMID:37917895

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Study of 2,881 Nasal Bone Fractures using Multivariate Analysis

Altern Ther Health Med. 2023 Nov 3:AT8863. Online ahead of print.

ABSTRACT

OBJECTIVE: This retrospective cohort study is aimed to provide a certain reference for the clinical prevention and treatment of nasal bone fracture, and further formulated a more perfect diagnosis and treatment plan.

METHODS: In detailed cases, 2881 patients with nasal bone fracture were recorded. Its general clinical data, cause of injury, fracture site, and fracture typing were collected through the database. All hospitalized patients admitted to the Ninth People’s Hospital Affiliated to the School of Medicine of Shanghai Jiao Tong University with integrated medical records could be retrospectively included from June 2013 to July 2018 and comprehensively analyzed for their gender, age, fracture type and cause of injury.

RESULTS: The sex ratio of nasal bone fracture was 2.44:1. The most patients with nasal bone fracture were 19-29 years old (35.6%). The injury rate of traffic accidents was the highest, 33.8%, followed by violent strikes, 24.1%. Statistical analysis showed that the number of patients with nasal bone combined with maxillary frontal bone fracture and type II nasal bone fracture was significantly higher than other fracture types. Logistic multiple regression analysis showed that the relative risk of nasal bone fracture in men was lower (odds ratio, OR = 0.807, P < .05), and the risk of nasal bone fracture decreased with age (OR = 0.978, P < .001). Compared with car accident injury, the relative risk of simple nasal bone fracture comes from violence, exercise or collision [OR = 1.244, P < .05; OR = 1.410, P < .05; OR = 1.453, P < .05]).

CONCLUSION: Given these findings, it’s evident that nasal bone fractures exhibit distinct patterns based on individual characteristics, causes of trauma, and injury site, and relevant strategy research should be conducted.

PMID:37917892