Patient-Reported Quality of Life for Osteoradionecrosis Reconstruction in the Head and Neck: A Longitudinal Framework and Risk Factors.

BACKGROUND: Osteoradionecrosis (ORN) is an aggressive sequela of head and neck cancer, treatment of which focuses on functional restoration and quality-of-life (QoL). This study aims to identify risks for poor QoL in ORN reconstruction and build a chronologic, longitudinal framework for QoL. METHODS: A prospective database of reconstructions performed by the senior author was reviewed from 2015-2023. QoL metrics (University of Washington [UWQoL]v4) were prospectively administered prior to surgery, one year post-operatively, and each yearly follow-up. RESULTS: 56 ORN patients were included (average 58.2years, mean 6,412Gy radiation). Reconstruction commonly was achieved with the fibula(55.4%) and anterolateral-thigh flaps(37.5%). The total complication rate was 23.2%, median 10.7mo post-operatively.Both "health-related QoL in comparison with prior to cancer diagnosis" (62.5 vs 43.5;p=0.030) and "Overall QoL during the past 7-days" (50.5 vs 41.7;p=0.029) were higher post-ORN reconstruction than before. Physical-QoL was higher pre-cancer reconstruction (79.0) than prior to ORN reconstruction (50.6;p<0.001) and following reconstruction (52.5;p=0.001). Social-emotional function was higher following ORN reconstruction compared to pre-reconstruction (68.7 vs 59.6;p=0.010).On multi-variate analysis, both post-operative social-emotional and physical function were impacted by betelnut use (p=0.038;p=0.025). Poor improvement in QoL from pre to post-ORN reconstruction were affected by maxilla involvement (p=0.048), fistula (p=0.004), and hardware issues (p=0.001). CONCLUSIONS: Our longitudinal experience trended decline in QoL at ORN diagnosis with gradual improvement following reconstruction, with eventual social-emotional, pain, anxiety, chewing, and global-QoL significantly improved following surgery. Betelnut was a risk factor for poor post-operative QoL. Maxillary involvement, post-op fistula and hardware issues were risks for non-improvement in QoL.

Clinical characteristics and risk factors of severe COVID-19 in hospitalized neonates with omicron variant infection: a retrospective study.

BACKGROUND: Reports on coronavirus disease 2019 (COVID-19) in neonates are limited, especially in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) Omicron variant. This study aims to analyze the clinical characteristics and identify risk factors associated with severe COVID-19 in neonates infected with Omicron variant. METHODS: The study population was represented by neonates with COVID-19, who were admitted to The Affiliated Children's Hospital of Xi'an Jiaotong University in northwest China, from December 10, 2022 to January 20, 2023. Chinese Center for Disease Control and Prevention (CDC) announced that all local COVID-19 cases were infected with Omicron variant during the study period. Clinical and laboratory data were collected retrospectively. We used logistic regression analysis to investigate the risk factors for severe COVID-19, and derived odds ratios (ORs) and the corresponding 95% confidence intervals (CIs). RESULTS: A total of 108 neonates, with median age of 18.1 days (interquartile range 9.4-23.0), were affected by COVID-19, of whom 84 had a mild disease, while 24 a severe one (22.2%). Of them, 6.5% were premature. No deaths were observed in the study population. The most common clinical manifestations were fever (88.9%) and cough (55.6%), with 5 cases (4.6%) complicated by pneumonia. 4 cases (3.7%) received respiratory support, including 2 cases of high-flow oxygen and 2 cases of continuous positive airway pressure. Gestational age at birth (OR: 0.615; 95% CI: 0.393-0.961), neutrophil count (NEU) (OR:0.576; 95% CI : 0.344-0.962) and lymphocyte count (LYM) (OR: 0.159; 95% CI: 0.063-0.401) were independent risk factors for severe COVID-19. The combination of NEU and LYM had the largest receiver operating characteristic area under the curve [0.912 (95% CI:0.830-0.993)] for identifying severe COVID-19, with a sensitivity of 0.833 and a specificity of 0.917. CONCLUSIONS: The general presentations and outcomes of neonatal COVID-19 caused by Omicron variant were not severe, and very few patients required respiratory support. The simultaneous decrease in NEU and LYM can be used to identify severe infection.

The Past, Present, and Future of Perforator Flaps in Head and Neck Surgery.

A perforator is a vessel that travels through muscle and perfuses the skin. Perforator flaps require intramuscular dissection and can be used as pedicled or free flap. With improved understanding of microvasculature, they can be tailored to have multiple skin paddles, multiple components, or shaped to conform to any defect. Reliable perforator flap-based reconstruction is a meticulous microvascular technique, ultimately allowing the surgeon to harvest any flap in a freestyle fashion and transplant to any recipient vessel. New technologies improve the safety and reproducibility of this type of reconstruction.

Free Latissimus Dorsi Flaps in Head and Neck Reconstruction at a Modern High-Volume Microsurgery Center.

BACKGROUND: Over the past two decades, with the introduction of the perforator flap concept and advances in flap dissections, lower extremities have emerged as the preferred soft tissue flap donor sites. As a modern and high-volume microsurgical center, and the senior author being one of the pioneers and advocates for the use of lower extremity flap donor sites, we aim to investigate the role of latissimus dorsi (LD) free flap in head and neck reconstruction within our current practice. METHODS: All free LD flaps used for head and neck reconstruction performed by a single surgeon between January 2010 and June 2023 were reviewed for their indications and immediate and short-term outcomes. RESULTS: A total of 1,586 head and neck free flap reconstructions were performed, and 33 free LD flaps were identified. The patients' median age was 53 (interquartile range [IQR] 48.5-63.5) years. Twenty-nine (87.9%) flaps were used to reconstruct oro-maxillo-facial and four (12.1%) flaps were used to reconstruct scalp defects. Most patients had prior radiation (n = 28, 84.8%), neck dissection (n = 24, 72.7%), and multiple previous head and neck flap reconstructions with a median of 3.0 (IQR 3.0-3.5) previous flaps. Six (18.2%) LD flaps were used to replace failed flaps from other donor sites. No major complications such as total flap failure or takebacks, and no need for vein grafts but three (9.1%) had flap marginal necrosis. Other complications included one flap dehiscence (3.0%), one orocutaneous fistula (3.0%), two wound infections (6.1%), three plate exposures (9.1%), and three patients who developed local recurrence (9.1%). The median patient follow-up time was 16 (IQR 5-27) months. CONCLUSION: This retrospective study demonstrates the role of LD free flap in head and neck reconstruction as a reliable and versatile backup soft tissue flap when workhorse flaps from lower extremity donor sites are either unavailable or unsuitable.

Hierarchical supramolecules composed of starch-based nanocluster aggregates with light-responsive mechanical strain for remotely rapid and precise actuation.

Hierarchical supramolecular systems, characterized by nanoscale sensitivity and macroscopic tangible changes, offer promising perspectives for the design of remotely controllable, rapid, and precise actuation materials, serving as a potential substitution for non-intelligent and complex actuation switches. Herein, we reported on the disassembly of orderly and rigid starch helical covalent structures, and their subsequent reassembly into a hierarchical supramolecular gel composed of nanocluster aggregates, integrating supramolecular interactions of three different scales. The incorporation of photo-sensitive FeIIITA, a complex of trivalent iron ions and tannic acid, significantly enhances the photo-responsive strain capacity of the hierarchical supramolecular gel. The supramolecular gel exhibits its features in a rapid light-responsive rate of hardness and viscosity, enabling the actuation of objects within 22 s under light exposure when employed as a remote actuation switch. Meanwhile, this actuation mechanism of the hierarchical supramolecular gel also has a promising perspective in precise control, identifying and actuating one of the two objects in distances of 0.8 mm even smaller scales. Our work provides a reliable reference for replacing complex actuation switches with intelligent materials for remote, rapid, and accurate actuation, and offers valuable insights for actuation in harsh and vacuum outdoor environments.

Quality-of-Life Outcomes in Oral Cancer Patients Reconstructed With Double Free Flaps: A Preoperative and Postoperative Assessment.

PURPOSE: This study aimed to evaluate quality of life (QOL) in patients with locally advanced oral cancer who underwent surgical resection followed by simultaneous double free flap reconstruction. METHODS: Institutional database was reviewed from 2015 to 2021 and prospectively collected University of Washington Quality of Life data that were extracted for patients who met the inclusion criteria. Mean, composite, and best percentage scores were computed. Wilcoxon signed rank test was used to analyze differences between groups. RESULTS: Thirteen patients completed the assessment, all of them being male with a mean follow-up of 2.2 ± 1.2 years. Most common double free flap combination was fibula osteoseptocutaneous flap and anterolateral thigh flap (n = 11). Improvement in pain ( P = 0.01) domain score with decline in speech ( P = 0.01) and taste ( P = 0.02) was noted along with an overall decline in QOL ( P = 0.001) after cancer diagnosis. A decrease in physical function was seen postoperatively. Chewing and saliva were the most cited postoperative patient-reported domain affecting QOL. CONCLUSIONS: In double free flap reconstructed patients, in the postoperative phase, pain scores improved, whereas speech and taste scores declined. The overall health-related QOL declined compared with before cancer diagnosis.

Sequential free fibula transfers: Quality of life and systematic review.

BACKGROUND: Successive osteoseptocutaneous fibula transfers for jaws reconstruction are rare but important options. This study contributes patient-reported and clinical outcomes, as well as systematically reviews all existing reports. METHODS: All sequential fibula transfers performed by the senior author were reviewed from a prospectively managed database, including University of Washington quality of life (UWQoL). Systematic review was conducted in PubMed and Cochrane databases for similar publications. RESULTS: Eighteen patients (average age 51.5 years) received sequential fibulas (mean 4.7 years between reconstructions). Secondary fibulas more often had benign indications (72.2% vs. 33.3%, p = .04), most commonly osteoradionecrosis (38.9%). At a mean follow-up of 30.5 months, the average interincisal distance increased from 21.8 to 27.6 mm, and 92.3% tolerated an oral diet following the second fibula. Eight patients completed the UW-QoL before and after the second fibula, and three prior to the first fibula. Composite physical function was significantly decreased from 96.7 prefibula reconstruction to 63.3 following the first (p < .001) and 64.2 after the second fibula (p < .001). There were no differences in other domains. The systematic review yielded six articles reporting 56 patients (mean 39 months between fibulas). Secondary fibulas were performed for repeat malignancy (45%) and osteoreadionecrosis (39%), resulting in elevated tube feeding from 20% following the first to 39% following the second, but overall high quality of life in two studies. CONCLUSIONS: Sequential osteoseptocutaneous fibula reconstructions of jaws are often performed for benign indications such as osteoradionecrosis. Overall function and QoL are comparable with those following the first fibula transfer.

Efficacy and safety of precision-guided transjugular extrahepatic portosystemic shunt (TEPS) in the management of cavernous transformation of the portal vein with portal hypertension: a case series.

BACKGROUND AND AIMS: Performing a Transjugular intrahepatic portal system shunt (TIPS) in patients with portal vein cavernous transformation (CTPV) poses significant challenges. As an alternative, transjugular extrahepatic portal vein shunt (TEPS) may offer a potential solution for these patients. Nonetheless, the effectiveness and safety of TEPS remain uncertain. This case series study aimed to evaluate the efficacy and safety of TEPS in treating patients with CTPV portal hypertension complications. METHODS: The study encompassed a cohort of 22 patients diagnosed with CTPV who underwent TEPS procedures. Of these, 13 patients manifested recurrent hemorrhagic episodes subsequent to conventional therapies, 8 patients grappled with recurrent or refractory ascites, and 1 patient experienced acute bleeding but refused endoscopic treatment. Comprehensive postoperative monitoring was conducted for all patients to rigorously evaluate both the technical and clinical efficacy of the intervention, as well as long-term outcomes. RESULTS: The overall procedural success rate among the 22 patients was 95.5% (21/22).During the TEPS procedure, nine patients were guided by percutaneous splenic access, three patients were guided by percutaneous hepatic access, five patients were guided by transmesenteric vein access from the abdomen, and two patients were guided by catheter marking from the hepatic artery. Additionally, guidance for three patients was facilitated by pre-existing TIPS stents. The postoperative portal pressure gradient following TEPS demonstrated a statistically significant decrease compared to preoperative values (24.95 ± 3.19 mmHg vs. 11.48 ± 1.74 mmHg, p < 0.01).Although three patients encountered perioperative complications, their conditions ameliorated following symptomatic treatment, and no procedure-related fatalities occurred. During a median follow-up period of 14 months, spanning a range of 5 to 39 months, we observed four fatalities. Specifically, one death was attributed to hepatocellular carcinoma, while the remaining three were ascribed to chronic liver failure. During the follow-up period, no instances of shunt dysfunction were observed. CONCLUSIONS: Precision-guided TEPS appears to be a safe and efficacious intervention for the management of CTPV.

Evaluation of models to predict prognosis in patients with advanced hepatocellular carcinoma treated with TACE combined with apatinib.

BACKGROUND: The HAP, Six-and-Twelve, Up to Seven, and ALBI scores have been substantiated as reliable prognostic markers in patients presenting with intermediate and advanced hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE) treatment. Given this premise, our research aims to assess the predictive efficacy of these models in patients with intermediate and advanced HCC receiving a combination of TACE and Apatinib. Additionally, we have conducted a meticulous comparative analysis of these four scoring systems to discern their respective predictive capacities and efficacies in combined therapy. METHODS: Performing a retrospective analysis on the clinical data from 200 patients with intermediate and advanced HCC, we studied those who received TACE combined with Apatinib at the First Affiliated Hospital of the University of Science and Technology of China between June 2018 and December 2022. To identify the factors affecting survival, the study performed univariate and multivariate Cox regression analyses, with calculations of four different scores: HAP, Six-and-Twelve, Up to Seven, and ALBI. Lastly, Harrell's C-index was employed to compare the prognostic abilities of these scores. RESULTS: Cox proportional hazards model results revealed that the ALBI score, presence of portal vein tumor thrombus (PVTT, )and tumor size are independent determinants of prognostic survival. The Kaplan-Meier analyses showed significant differences in survival rates among patients classified by the HAP, Six-and-Twelve, Up to Seven, and ALBI scoring methods. Of the evaluated systems, the HAP scoring demonstrated greater prognostic precision, with a Harrell's C-index of 0.742, surpassing the alternative models (P < 0.05). In addition, an analysis of the area under the AU-ROC curve confirms the remarkable superiority of the HAP score in predicting short-term survival outcomes. CONCLUSION: Our study confirms the predictive value of HAP, Six-and-Twelve, Up to Seven, and ALBI scores in intermediate to advanced Hepatocellular Carcinoma (HCC) patients receiving combined Transarterial Chemoembolization (TACE) and Apatinib therapy. Notably, the HAP model excels in predicting outcomes for this specific HCC subgroup.

Evaluating Head and Neck Reconstruction Outcomes Proves Difficult-Seeking Improvement in Reporting.

This Viewpoint advocates for the improvement of the quality of head and neck reconstruction studies through accurate depictions of the defect and reconstruction performed.

Evolution of free flap reconstruction in the upper extremity: perspective from a tertiary plastic and reconstructive institution.

Soft tissue reconstruction of the upper extremity requires consideration of wound bed status, varied anatomic composition, future function and tissue match, whether in thickness, pliability or involvement of other tissue components. Of the options available, microvascular free tissue flaps allow maximal customizability with the avoidance of long-term donor site morbidity. Free tissue transfers have evolved, given increased surgical proficiency, from direct vessel-based flaps to septocutaneous vessel-based flaps, to musculocutaneous perforator flaps, and most recently to free-style free flaps. With increases in technical complexity come limitless alternatives. We documented the progression of free flap upper extremity reconstruction in recreating form and function of the upper extremity. The foundations laid should allow surgeons the freedom and versatility to choose the most faithful restoration of the defect and produce the best functional and aesthetic results.

Liver abscess after drug-eluting bead transarterial chemoembolization for hepatic malignant tumors: Clinical features, pathogenesis, and management.

AIM: The study aimed to investigate the clinical features, incidence, pathogenesis, and management of liver abscess after drug-eluting bead transarterial chemoembolization (DEB-TACE) for primary and metastatic hepatic malignant tumors. METHODS: From June 2019 to June 2021, patients with liver abscess after DEB-TACE for primary and metastatic hepatic malignant tumors were reviewed and evaluated at our hospital. Demographic and clinical data, radiological findings, management approaches, and prognosis were retrospectively analyzed. RESULTS: In total, 419 DEB-TACE procedures were carried out in 314 patients with primary and metastatic liver tumors at our medical center. Twelve patients were confirmed to have liver abscesses after DEB-TACE through clinical manifestations, laboratory investigations, and imaging. In this study, the incidence of liver abscess was 3.82% per patient and 2.86% per DEB-TACE procedure. After percutaneous drainage and anti-inflammatory treatments, 10 patients recovered, and the remaining 2 patients died due to direct complications of liver abscess, such as sepsis and multiple organ failure. The mortality rate of liver abscesses after DEB-TACE was 16.7% (2/12). CONCLUSION: The incidence of liver abscess after DEB-TACE is relatively high and can have serious consequences, including death. Potential risk factors could include large tumor size, history of bile duct or tumor resection, history of diabetes, small DEB size (100-300 µm). Sensitive antibiotics therapy and percutaneous abscess aspiration/drainage are effective treatments for liver abscess after DEB-TACE.

Value of salivary gland imaging based on deep learning and Delta radiomics in evaluation of salivary gland injury following 131I therapy post thyroid cancer surgery / 中华核医学与分子影像杂志

Objective:To explore the value of salivary gland imaging based on deep learning and Delta radiomics in assessing salivary gland injury after 131I treatment in post-thyroidectomy thyroid cancer patients. Methods:A retrospective analysis on 223 patients (46 males, 177 females, age(47.7±14.0) years ) with papillary thyroid cancer, who underwent total thyroidectomy and 131I treatment in Affiliated Hospital of Guilin Medical University between December 2019 and January 2022, was conducted. All patients underwent salivary gland 99Tc mO 4- imaging before and after 131I therapy. The patients were categorized according to salivary gland function based on 99Tc mO 4- imaging results (normal salivary gland vs salivary gland injury), and divided into training and test sets in a ratio of 7∶3. A ResNet-34 neural network model was trained using images at the time of maximum salivary gland radioactivity and those based on background radioactivity counts for structured image feature data. The Delta radiomics approach was then used to subtract the image feature values of the two periods, followed by feature selection through t-test, correlation analysis, and the least absolute shrinkage and selection operator( LASSO) algorithm, to develop logistic regression (LR), support vector machine (SVM), and K-nearest neighbor (KNN) predictive models. The diagnostic performance of 3 models for salivary gland function on the test set was compared with that of the manual interpretation. The AUCs of the 3 models on the test set were compared (Delong test). Results:Among the 67 cases of the test set, the diagnostic accuracy of 3 physicians were 89.6%(60/67), 83.6%(56/67), and 82.1%(55/67) respectively, with the time required for diagnosis of 56, 74 and 55 min, respectively. The accuracies of LR, SVM, and KNN models were 91.0%(61/67), 86.6%(58/67), and 82.1%(55/67), with the required times of 12.5, 15.3 and 17.9 s, respectively. All 3 radiomics models demonstrated good classification and predictive capabilities, with AUC values for the training set of 0.972, 0.965, and 0.943, and for the test set of 0.954, 0.913, and 0.791, respectively. There were no significant differences among the AUC values for the test set ( z values: 0.72, 1.18, 1.82, all P>0.05). Conclusion:The models based on deep learning and Delta radiomics possess high predictive value in assessing salivary gland injury following 131I treatment after surgery in patients with thyroid cancer.

Research progress of vagus nerve in regulation of inflammatory response in sepsis / 中华危重病急救医学

The vagus nerve, as an important "guardian" of the body, is involved in the steady-state regulation of cardiovascular, respiratory, gastrointestinal digestion and endocrine systems. Recent studies have shown that the vagus nerve plays an important regulatory role in inflammatory response via the inflammatory reflex, which is closely related to the fact that the afferent and efferent fibers of the vagus nerve can sense and regulate inflammation, respectively. The pathophysiological mechanism of sepsis is based on the dysregulation of immune response, and it is often initiated by the excessive inflammatory response of the innate immune system. In recent years, in order to expand intervention strategies for the immune dysregulation of sepsis, researchers have made many efforts on regulating the inflammatory response of the vagus nerve in sepsis. This article focuses on the mechanism of vagus nerve-mediated inflammatory reflex and the regulatory role of vagus nerve in inflammatory response of sepsis, in order to reveal new therapeutic strategies for the treatment of sepsis.

Reflections on improving drug success rates with AIDD and CADD / 中国药科大学学报

@#Abstract: The rapid advancements in artificial intelligence (AI) and computational sciences, particularly through the introduction of artificial intelligence drug design (AIDD) and computer-aided drug design (CADD) technologies, have revolutionized pathways in drug development. These include techniques such as natural language processing, image recognition, deep learning, and machine learning. By employing advanced algorithms and data processing techniques, these technologies have significantly enhanced the efficiency and success rate of R&D processes. In drug discovery, AI technologies have accelerated the identification of drug targets, screening of candidate drugs, pharmacological assessments, and quality control, effectively reducing R&D risks and costs. This article delves into the application of AIDD and CADD in drug development, analyzing their roles in enhancing the success rates and efficiencies of drug design, exploring their future trends, and addressing the potential challenges.

Classification of Atretic Small Antral Follicles in the Human Ovary.

The reproductive lifespan in humans is regulated by a delicate cyclical balance between follicular recruitment and atresia in the ovary. The majority of the small antral follicles present in the ovary are progressively lost through atresia without reaching dominance, but this process remains largely underexplored. In our study, we investigated the characteristics of atretic small antral follicles and proposed a classification system based on molecular changes observed in granulosa cells, theca cells, and extracellular matrix deposition. Our findings revealed that atresia spreads in the follicle with wave-like dynamics, initiating away from the cumulus granulosa cells. We also observed an enrichment of CD68+ macrophages in the antrum during the progression of follicular atresia. This work not only provides criteria for classifying three stages of follicular atresia in small antral follicles in the human ovary but also serves as a foundation for understanding follicular degeneration and ultimately preventing or treating premature ovarian failure. Understanding follicular remodeling in the ovary could provide a means to increase the number of usable follicles and delay the depletion of the follicular reserve, increasing the reproductive lifespan.

Association of hepatitis B virus DNA levels with efficacy and safety outcomes in patients with hepatitis B virus-associated advanced hepatocellular carcinoma receiving tyrosine kinase inhibitor plus anti-PD-1 antibody: a multicenter propensity-matched study.

BACKGROUND: The efficacy and safety of tyrosine kinase inhibitors (TKIs) combined with anti-PD-1 antibodies (α-PD-1) in advanced hepatocellular carcinoma (HCC) with high hepatitis B virus (HBV) DNA levels (>500 IU/mL) remain unclear. METHODS: We retrospectively assessed patients from seven medical institutions diagnosed with HBV-related HCC, undergoing treatment with TKIs and α-PD-1 in conjunction with antiviral therapies. Based on HBV-DNA levels, patients were categorized into either high (HHBV-DNA, >500 IU/mL) or low HBV-DNA (LHBV-DNA, ≤500 IU/mL) cohorts Propensity score matching (PSM) was used to minimize baseline imbalance between groups. RESULTS: 149 patients were included, with 66 patients exhibiting HBV-DNA > 500 IU/mL and 83 patients presenting HBV-DNA ≤ 500 IU/mL. Compared with the LHBV-DNA cohort, the HHBV-DNA cohort had a greater incidence of serum HBeAg positivity, tumor diameter ≥ 10 cm, and vascular invasion. Following PSM, 57 individuals were enrolled in each group. Oncological outcomes were comparable between HHBV-DNA and LHBV-DNA cohorts before and after PSM. Before PSM, the median PFS and OS were 6.1 months and 17.5 months in the HHBV-DNA cohort and 6.7 months and 19.3 months in the LHBV-DNA cohort (all P > 0.05). After PSM, the median PFS and OS were 6.0 months and 19.5 months in the HHBV-DNA cohort and 6.0 months and 17.1 months in the LHBV-DNA cohort, respectively (all P > 0.05). Safety profiles were equivalent across cohorts with no fatal incidents reported. Seven patients (4.7 %) had HBV reactivation. 1 (0.7 %) from HHBV-DNA and 6 (4.0 %) from LHBV-DNA (P = 0.134). Only one patient developed HBV-related hepatitis. CONCLUSIONS: The effectiveness and safety of TKIs plus α-PD-1 in advanced HCC with HBV-DNA > 500 IU/mL were not compromised in the context of concomitant antiviral therapy.