Background: Hearing loss (HL) is one of the most common sensory disorders, affecting over 5-8% of the world's population. Approximately half of HL cases are attributed to genetic factors. In hereditary deafness, about 75-80% is inherited through autosomal recessive inheritance, and common pathogenic genes include GJB2 and SLC26A4. Pathogenic variants in the SLC26A4gene are the leading cause of hereditary hearing loss in humans, second only to the GJB2 gene. Variants in the SLC26A4gene cause hearing loss, which can be non-syndromic autosomal recessive deafness (DFNB4, OMIM #600791) associated with enlarged vestibular aqueduct (EVA) or Pendred syndrome (Pendred, OMIM #605646). DFNB4 is characterized by sensorineural hearing loss combined with EVA or less common cochlear malformation defect. Pendred syndrome is characterized by bilateral sensorineural hearing loss with EVA and an iodine defect that can lead to thyroid goiter. Currently, it is known that EVA is associated with variants in the SLC26A4 gene and is a penetrant feature of SLC26A4-related HL. Predominant mutations in these genes differ significantly across populations. For instance, predominant SLC26A4 mutations differ among populations, including p.T416P and c.1001G>A in Caucasians, p.H723R in Japanese and Koreans, and c.919-2A>G in Han Taiwanese and Han Chinese. On the other hand, there has been no study of hearing loss related to SLC26A4 gene variants among Mongolians, which is the basis of our research. Aim: We aimed to identify the characteristics of the SLC26A4 gene variants in Mongolian people with Enlarged vestibular aqueduct and Mondini malformation. Materials and Methods: In 2022-2024, We included 13 people with hearing loss and enlarged vestibular aqueduct, incomplete cochlea (1.5 turns of the cochlea with cystic apex- incomplete partition type II- Mondini malformation) were examined by CT scan of the temporal bone in our study. WES (Whole exome sequencing) analysis was performed in the Genetics genetic-laboratory of the National Taiwan University Hospital. Results: Genetic analysis revealed 26 confirmed pathogenic variants of bi-allelic SLC26A4 gene of 8 different types in 13 cases, and c.919-2A>G variant was dominant with 46% (12/26) in allele frequency, and c.2027T>A (p.L676Q) variant 19% (5/26), c.1318A>T(p.K440X) variant 11% (3/26), c.1229C>T (p.T410M) variant 8% (2/26) ) , c.716T>A (p.V239D), c.281C>T (p.T94I), c.1546dupC, and c.1975G>C (p.V659L) variants were each 4% (1/26)- revealed. Two male children, 11 years old (SLC26A4: c.919-2A>G) and 7 years old (SLC26A4: c.919-2A>G:, SLC26A4: c.2027T>A (p.L676Q))had history of born normal hearing and progressive hearing loss. Conclusions 1. 26 variants of bi-allelic SLC26A4 gene mutation were detected in Mongolian people with EVA and Mondini malformation, and c.919-2A>G was the most dominant allele variant, and rare variants such as c.1546dupC, c.716T>A (p.V239D) were detected. 2. Our study shows that whole-exome sequencing (WES) can identify gene mutations that are not detected by polymerase chain reaction (PCR) or NGS analysis.

Background: Current regional anesthesia techniques used to anesthetize the intercostobrachial nerve (ICBN) for upper arm surgery either lack reliability or have increased procedural risks. Safer and more reliable regional anesthetic techniques are required to block the ICBN effectively. Here, we introduce a novel “axillary serratus anterior plane (A-SAP) block” for anesthetizing the ICBN to allow surgical anesthesia for upper arm arteriovenous fistula (UA-AVF) creation. Case: We present 3 cases involving a 79-year-old Chinese male, a 73-year-old Malay female, and a 38-year-old Chinese male, in which the A-SAP block was utilized in UA-AVF creation surgeries. In all 3 cases, the A-SAP block was performed in combination with a supraclavicular brachial plexus block. None of the patients required local anesthetic supplementation intraoperatively. Conclusions The A-SAP block reliably and safely anesthetized the ICBN for UA-AVF creation surgery and is a reliable alternative to higher-risk block techniques, such as paravertebral block or neuraxial block.

Background: Current regional anesthesia techniques used to anesthetize the intercostobrachial nerve (ICBN) for upper arm surgery either lack reliability or have increased procedural risks. Safer and more reliable regional anesthetic techniques are required to block the ICBN effectively. Here, we introduce a novel “axillary serratus anterior plane (A-SAP) block” for anesthetizing the ICBN to allow surgical anesthesia for upper arm arteriovenous fistula (UA-AVF) creation. Case: We present 3 cases involving a 79-year-old Chinese male, a 73-year-old Malay female, and a 38-year-old Chinese male, in which the A-SAP block was utilized in UA-AVF creation surgeries. In all 3 cases, the A-SAP block was performed in combination with a supraclavicular brachial plexus block. None of the patients required local anesthetic supplementation intraoperatively. Conclusions The A-SAP block reliably and safely anesthetized the ICBN for UA-AVF creation surgery and is a reliable alternative to higher-risk block techniques, such as paravertebral block or neuraxial block.

Objective: Patients with severe symptomatic aortic stenosis are assessed for coronary artery disease (CAD) prior to transcatheter aortic valve implantation (TAVI) with treatment implications. Invasive coronary angiography (ICA) is the recommended modality but is associated with peri-procedural complications. Integrating machine learning (ML)-based computed tomography-derived fractional flow reserve (CT-FFR) into existing TAVI-planning CT protocol may aid exclusion of significant CAD and thus avoiding ICA in selected patients. Materials and Methods: A single-center, retrospective study was conducted, 41 TAVI candidates with both TAVI-planning CT and ICA performed were analyzed. CT datasets were evaluated by a ML-based CT-FFR software. Beta-blocker and nitroglycerin were not administered in these patients. The primary outcome was to identify significant CAD. The diagnostic performance of CT-FFR was compared against ICA. Results: On per-patient level, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy were 89%, 94%, 80%, 97% and 93%, respectively. On per-vessel level, the sensitivity, specificity, PPV, NPV and diagnostic accuracy were 75%, 94%, 67%, 96% and 92%, respectively. The area under the receiver operative characteristics curve per individual coronary vessels yielded overall 0.90 (95% confidence interval 85%–95%). ICA may be avoided in up to 80% of patients if CT-FFR results were negative. Conclusion ML-based CT-FFR can provide accurate screening capabilities for significant CAD thus avoiding ICA. Its integration to existing TAVI-planning CT is feasible with the potential of improving the safety and efficiency of pre-TAVI CAD assessment.

Background: Current regional anesthesia techniques used to anesthetize the intercostobrachial nerve (ICBN) for upper arm surgery either lack reliability or have increased procedural risks. Safer and more reliable regional anesthetic techniques are required to block the ICBN effectively. Here, we introduce a novel “axillary serratus anterior plane (A-SAP) block” for anesthetizing the ICBN to allow surgical anesthesia for upper arm arteriovenous fistula (UA-AVF) creation. Case: We present 3 cases involving a 79-year-old Chinese male, a 73-year-old Malay female, and a 38-year-old Chinese male, in which the A-SAP block was utilized in UA-AVF creation surgeries. In all 3 cases, the A-SAP block was performed in combination with a supraclavicular brachial plexus block. None of the patients required local anesthetic supplementation intraoperatively. Conclusions The A-SAP block reliably and safely anesthetized the ICBN for UA-AVF creation surgery and is a reliable alternative to higher-risk block techniques, such as paravertebral block or neuraxial block.

Background: Current regional anesthesia techniques used to anesthetize the intercostobrachial nerve (ICBN) for upper arm surgery either lack reliability or have increased procedural risks. Safer and more reliable regional anesthetic techniques are required to block the ICBN effectively. Here, we introduce a novel “axillary serratus anterior plane (A-SAP) block” for anesthetizing the ICBN to allow surgical anesthesia for upper arm arteriovenous fistula (UA-AVF) creation. Case: We present 3 cases involving a 79-year-old Chinese male, a 73-year-old Malay female, and a 38-year-old Chinese male, in which the A-SAP block was utilized in UA-AVF creation surgeries. In all 3 cases, the A-SAP block was performed in combination with a supraclavicular brachial plexus block. None of the patients required local anesthetic supplementation intraoperatively. Conclusions The A-SAP block reliably and safely anesthetized the ICBN for UA-AVF creation surgery and is a reliable alternative to higher-risk block techniques, such as paravertebral block or neuraxial block.

A biosynthetic gene cluster for the bioactive fungal sesterterpenoids variecolin ( 1) and variecolactone ( 2) was identified in Aspergillus aculeatus ATCC 16872. Heterologous production of 1 and 2 was achieved in Aspergillus oryzae by expressing the sesterterpene synthase VrcA and the cytochrome P450 VrcB. Intriguingly, the replacement of VrcB with homologous P450s from other fungal terpenoid pathways yielded three new variecolin analogues ( 5- 7). Analysis of the compounds' anticancer activity in vitro and in vivo revealed that although 5 and 1 had comparable activities, 5 was associated with significantly reduced toxic side effects in cancer-bearing mice, indicating its potentially broader therapeutic window. Our study describes the first tests of variecolin and its analogues in animals and demonstrates the utility of synthetic biology for creating molecules with improved biological activities.

BACKGROUND:This study aimed to evaluate the discriminatory performance of 11 vital sign-based early warning scores(EWSs)and three shock indices in early sepsis prediction in the emergency department(ED). METHODS:We performed a retrospective study on consecutive adult patients with an infection over 3 months in a public ED in Hong Kong.The primary outcome was sepsis(Sepsis-3 definition)within 48 h of ED presentation.Using c-statistics and the DeLong test,we compared 11 EWSs,including the National Early Warning Score 2(NEWS2),Modified Early Warning Score,and Worthing Physiological Scoring System(WPS),etc.,and three shock indices(the shock index[SI],modified shock index[MSI],and diastolic shock index[DSI]),with Systemic Inflammatory Response Syndrome(SIRS)and quick Sequential Organ Failure Assessment(qSOFA)in predicting the primary outcome,intensive care unit admission,and mortality at different time points. RESULTS:We analyzed 601 patients,of whom 166(27.6%)developed sepsis.NEWS2 had the highest point estimate(area under the receiver operating characteristic curve[AUROC]0.75,95%CI 0.70-0.79)and was significantly better than SIRS,qSOFA,other EWSs and shock indices,except WPS,at predicting the primary outcome.However,the pooled sensitivity and specificity of NEWS2≥5 for the prediction of sepsis were 0.45(95%CI 0.37-0.52)and 0.88(95%CI 0.85-0.91),respectively.The discriminatory performance of all EWSs and shock indices declined when used to predict mortality at a more remote time point. CONCLUSION:NEWS2 compared favorably with other EWSs and shock indices in early sepsis prediction but its low sensitivity at the usual cut-off point requires further modification for sepsis screening.

BACKGROUND:This study aimed to evaluate the discriminatory performance of 11 vital sign-based early warning scores(EWSs)and three shock indices in early sepsis prediction in the emergency department(ED). METHODS:We performed a retrospective study on consecutive adult patients with an infection over 3 months in a public ED in Hong Kong.The primary outcome was sepsis(Sepsis-3 definition)within 48 h of ED presentation.Using c-statistics and the DeLong test,we compared 11 EWSs,including the National Early Warning Score 2(NEWS2),Modified Early Warning Score,and Worthing Physiological Scoring System(WPS),etc.,and three shock indices(the shock index[SI],modified shock index[MSI],and diastolic shock index[DSI]),with Systemic Inflammatory Response Syndrome(SIRS)and quick Sequential Organ Failure Assessment(qSOFA)in predicting the primary outcome,intensive care unit admission,and mortality at different time points. RESULTS:We analyzed 601 patients,of whom 166(27.6%)developed sepsis.NEWS2 had the highest point estimate(area under the receiver operating characteristic curve[AUROC]0.75,95%CI 0.70-0.79)and was significantly better than SIRS,qSOFA,other EWSs and shock indices,except WPS,at predicting the primary outcome.However,the pooled sensitivity and specificity of NEWS2≥5 for the prediction of sepsis were 0.45(95%CI 0.37-0.52)and 0.88(95%CI 0.85-0.91),respectively.The discriminatory performance of all EWSs and shock indices declined when used to predict mortality at a more remote time point. CONCLUSION:NEWS2 compared favorably with other EWSs and shock indices in early sepsis prediction but its low sensitivity at the usual cut-off point requires further modification for sepsis screening.

BACKGROUND:This study aimed to evaluate the discriminatory performance of 11 vital sign-based early warning scores(EWSs)and three shock indices in early sepsis prediction in the emergency department(ED). METHODS:We performed a retrospective study on consecutive adult patients with an infection over 3 months in a public ED in Hong Kong.The primary outcome was sepsis(Sepsis-3 definition)within 48 h of ED presentation.Using c-statistics and the DeLong test,we compared 11 EWSs,including the National Early Warning Score 2(NEWS2),Modified Early Warning Score,and Worthing Physiological Scoring System(WPS),etc.,and three shock indices(the shock index[SI],modified shock index[MSI],and diastolic shock index[DSI]),with Systemic Inflammatory Response Syndrome(SIRS)and quick Sequential Organ Failure Assessment(qSOFA)in predicting the primary outcome,intensive care unit admission,and mortality at different time points. RESULTS:We analyzed 601 patients,of whom 166(27.6%)developed sepsis.NEWS2 had the highest point estimate(area under the receiver operating characteristic curve[AUROC]0.75,95%CI 0.70-0.79)and was significantly better than SIRS,qSOFA,other EWSs and shock indices,except WPS,at predicting the primary outcome.However,the pooled sensitivity and specificity of NEWS2≥5 for the prediction of sepsis were 0.45(95%CI 0.37-0.52)and 0.88(95%CI 0.85-0.91),respectively.The discriminatory performance of all EWSs and shock indices declined when used to predict mortality at a more remote time point. CONCLUSION:NEWS2 compared favorably with other EWSs and shock indices in early sepsis prediction but its low sensitivity at the usual cut-off point requires further modification for sepsis screening.