Retrospective analysis based on a clinical grading system for patients with hepatic hemangioma: A single center experience.

BACKGROUND: The optimal approach for managing hepatic hemangioma is controversial. AIM: To evaluate a clinical grading system for management of hepatic hemangioma based on our 17-year of single institution experience. METHODS: A clinical grading system was retrospectively applied to 1171 patients with hepatic hemangioma from January 2002 to December 2018. Patients were classified into four groups based on the clinical grading system and treatment: (1) Observation group with score < 4 (Obs score < 4); (2) Surgical group with score < 4 (Sur score < 4); (3) Observation group with score ≥ 4 (Obs score ≥ 4); and (4) Surgical group with score ≥ 4 (Sur score ≥ 4). The clinico-pathological index and outcomes were evaluated. RESULTS: There were significantly fewer symptomatic patients in surgical groups (Sur score ≥ 4 vs Obs score ≥ 4, P < 0.001; Sur score < 4 vs Obs score < 4, χ² = 8.60, P = 0.004; Sur score ≥ 4 vs Obs score < 4, P < 0.001). The patients in Sur score ≥ 4 had a lower rate of in need for intervention and total patients with adverse event than in Obs score ≥ 4 (P < 0.001; P < 0.001). Nevertheless, there was no significant difference in need for intervention and total patients with adverse event between the Sur score < 4 and Obs score < 4 (P > 0.05; χ² = 1.68, P > 0.05). CONCLUSION: This clinical grading system appeared as a practical tool for hepatic hemangioma. Surgery can be suggested for patients with a score ≥ 4. For those with < 4, follow-up should be proposed.

Learning curve stratified outcomes after robotic pancreatoduodenectomy: International multicenter experience.

BACKGROUND: Robotic pancreatoduodenectomy is increasingly being implemented worldwide, with good results reported from individual expert centers. However, it is unclear to what extent outcomes will continue to improve during the learning curve, as large international studies are lacking. METHODS: An international retrospective multicenter case series, including consecutive patients after robotic pancreatoduodenectomy from 18 centers in 8 countries in Europe, Asia, and South America until December 31, 2019, was conducted. A cumulative sum analysis was performed to determine the inflection points for the feasibility (operative time and blood loss) and proficiency (postoperative pancreatic fistula grade B/C and major morbidity) learning curves. Outcomes were compared in 3 groups on the basis of the learning curve inflection points. RESULTS: Overall, 2,186 patients after robotic pancreatoduodenectomy were included. The feasibility learning curve was reached after 30-45 robotic pancreatoduodenectomy procedures and the proficiency learning curve after 90 robotic pancreatoduodenectomy procedures. These inflection points created 3 phases, which were associated with major morbidity (24.7%, 23.4%, and 12.3%, P < .001) but not 30-day mortality (2.1%, 2.0%, and 1.5%, P = .670). Other outcomes mostly continued to improve, including median operative time 432, 390, and 300 minutes (P < .0001), conversion 6.0%, 4.7%, and 2.7% (P = .002), bile leakage 7.2%, 4.1%, and 2.4% (P < .001), postpancreatectomy hemorrhage 6.5%, 6.1%, and 1.8% (n = 21) but not R0 resection (pancreatic ductal adenocarcinoma only) 78.5%, 73.9%, and 82.8% (P = .35), and 90-day mortality rate 3.1%, 3.5%, and 2.1% (P = .191). Centers performing >20 robotic pancreatoduodenectomies annually had lower rates of conversion, reoperation, and shorter median operative time as compared with centers performing 10-20 robotic pancreatoduodenectomies annually. CONCLUSION: This international multicenter study demonstrates that most outcomes of robotic pancreatoduodenectomy continued to improve during 3 learning curve phases without a negative effect on 90-day mortality. Randomized studies are needed in high-volume centers that have surpassed the first learning curves, to compare these outcomes with the open approach.

The effect of low-dose ketamine on electroencephalographic spectrum during gynecology surgery under desflurane anesthesia.

BACKGROUND: The perioperative administration of low-dose ketamine has shown potential in postoperative pain management, opioid sparing, and enhancing pain control. This study aimed to investigate the impact of low-dose ketamine on processed electroencephalography (EEG) signals during anesthesia. METHODS: Forty patients with American Society of Anesthesiologists physical status I-II undergoing elective gynecological surgery were enrolled. EEG monitoring was initiated upon induction of anesthesia. Anesthesia was maintained with desflurane and alfentanil immediately after induction. Fifteen minutes after induction, the ketamine group received a 0.3 mg/kg bolus followed by 0.05 mg/kg/h infusion until completion of surgery. The control group received equivalent saline. Postoperative assessments included pain score (visual analog scale), morphine usage, and quality of recovery. RESULTS: The ketamine group had significantly higher Patient State Index (PSi) values at 10, 20, and 30 minutes after ketamine administration compared to the controls. Ketamine administration led to significant alterations in EEG patterns, including reduced relative power in delta and theta frequency bands, and increased relative power in beta and gamma frequency bands at 10 minutes post-administration. Relative power in the alpha frequency band significantly decreased at 10, 20, and 30 minutes post-administration. However, there were no differences in intraoperative alfentanil consumption, postoperative morphine usage, and pain scores between the two groups. CONCLUSION: Low-dose ketamine administration during desflurane anesthesia led to notable changes in EEG patterns and PSi values. These findings provide valuable insights into the impact of ketamine on brain activity, and offer essential information for clinical anesthesiologists.

Paraneoplastic dermatomyositis and Hodgkin's lymphoma in a 14-year-old girl: a case report and literature review.

Background: Juvenile dermatomyositis (JDM) is a rare autoimmune myopathy whose main clinical manifestations include a characteristic rash, symmetrical proximal muscle weakness, and elevated muscle enzymes. While approximately one-third of adult patients with dermatomyositis (DM) develop malignancies, typically within a year of diagnosis, this phenomenon is not commonly observed in patients with JDM. In this study, we present a rare case of both JDM and Hodgkin's lymphoma (HL) diagnosed in an adolescent female patient. Case description: A 14-year-old girl with proximal muscle weakness and myalgia for 8 weeks was admitted to the hospital and ultimately received a diagnosis of DM. A thorough physical examination revealed enlarged lymph nodes on both sides of the cervical, and a lymph node biopsy was performed to diagnose HL. After she underwent radiotherapy and chemotherapy, her symptoms of both HL and DM were alleviated. Conclusion: The phenomenon of JDM as a paraneoplastic syndrome associated with HL is very rare. Thus, routine cancer screening for DM in adolescents is currently not recommended. The diagnosis of JDM requires a detailed physical examination, and further tumor screening is necessary for patients with unusual physical findings, such as atypical rashes, enlarged lymph nodes, and enlargement of the spleen and/or liver. Even if no malignancy is detected when JDM is diagnosed, long-term follow-up is necessary.

Lung ultrasound score evaluation of the effect of pressure-controlled ventilation volume-guaranteed on patients undergoing laparoscopic-assisted radical gastrectomy.

BACKGROUND: Laparoscopic-assisted radical gastrectomy (LARG) is the standard treatment for early-stage gastric carcinoma (GC). However, the negative impact of this procedure on respiratory function requires the optimized intraoperative management of patients in terms of ventilation. AIM: To investigate the influence of pressure-controlled ventilation volume-guaranteed (PCV-VG) and volume-controlled ventilation (VCV) on blood gas analysis and pulmonary ventilation in patients undergoing LARG for GC based on the lung ultrasound score (LUS). METHODS: The study included 103 patients with GC undergoing LARG from May 2020 to May 2023, with 52 cases undergoing PCV-VG (research group) and 51 cases undergoing VCV (control group). LUS were recorded at the time of entering the operating room (T0), 20 minutes after anesthesia with endotracheal intubation (T1), 30 minutes after artificial pneumoperitoneum (PP) establishment (T2), and 15 minutes after endotracheal tube removal (T5). For blood gas analysis, arterial partial pressure of oxygen (PaO2) and partial pressure of carbon dioxide (PaCO2) were observed. Peak airway pressure (Ppeak), plateau pressure (Pplat), mean airway pressure (Pmean), and dynamic pulmonary compliance (Cdyn) were recorded at T1 and T2, 1 hour after PP establishment (T3), and at the end of the operation (T4). Postoperative pulmonary complications (PPCs) were recorded. Pre- and postoperative serum interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α (TNF-α) were measured by enzyme-linked immunosorbent assay. RESULTS: Compared with those at T0, the whole, anterior, lateral, posterior, upper, lower, left, and right lung LUS of the research group were significantly reduced at T1, T2, and T5; in the control group, the LUS of the whole and partial lung regions (posterior, lower, and right lung) decreased significantly at T2, while at T5, the LUS of the whole and some regions (lateral, lower, and left lung) increased significantly. In comparison with the control group, the whole and regional LUS of the research group were reduced at T1, T2, and T5, with an increase in PaO2, decrease in PaCO2, reduction in Ppeak at T1 to T4, increase in Pmean and Cdyn, and decrease in Pplat at T4, all significant. The research group showed a significantly lower incidence of PPCs than the control group within 3 days postoperatively. Postoperative IL-1ß, IL-6, and TNF-α significantly increased in both groups, with even higher levels in the control group. CONCLUSION: LUS can indicate intraoperative non-uniformity and postural changes in pulmonary ventilation under PCV-VG and VCV. Under the lung protective ventilation strategy, the PCV-VG mode more significantly improved intraoperative lung ventilation in patients undergoing LARG for GC and reduced lung injury-related cytokine production, thereby alleviating lung injury.

Recommendations and guidance for herpes zoster vaccination for adults in Taiwan.

Herpes zoster (HZ) is a painful, vesicular, cutaneous eruption from reactivation of varicella zoster virus (VZV), which can lead to potentially debilitating complications. The lifetime risk of HZ is estimated to be 20%-30% in the general population, with an increased risk in the elderly and immunocompromised populations. The most effective strategy to prevent HZ and its complications is by vaccination. Two types of HZ vaccines, zoster vaccine live and recombinant zoster vaccine, have been approved for use. This guidance offers recommendations and suggestions for HZ vaccination in adults, aiming to reduce the disease burden of HZ and its complications. It is intended as a guide to first-line healthcare providers, but does not supersede clinical judgement when assessing risk and providing recommendations to individuals. The Working Group on Adult Immunization Practice was appointed by the Infectious Diseases Society of Taiwan (IDST) and recommendations were drafted after a full literature review, using the Grading of Recommendation, Assessment, Development and Evaluation (GRADE) system. The recommendations were reviewed and revised by expert review panels during a series of consensus meetings and endorsed by the IDST, Taiwan Association of Family Medicine, the Taiwanese Dermatological Association, the Taiwan Oncology Society, the Taiwan Society of Blood and Marrow Transplantation, the Transplantation Society of Taiwan, the Taiwan AIDS Society, and the Taiwan College of Rheumatology. This guidance describes the epidemiology of HZ and provides recommendations for HZ vaccination in adults with varying levels of risk, differing history of previous VZV infection and past varicella or zoster vaccinations.

Survival outcome and prognostic factors of remnant gastric cancer: a propensity score-matched analysis.

Background: Studies on survival and prognostic factors in individuals with remnant gastric cancer (RGC) after gastric cancer (GC) are rare. It is debatable whether prognosis of RGC after GC is worse than that of only primary GC (OPGC). The objective of this study is to compare the survival outcomes between post-GC RGC and OPGC undergoing surgical resection and to identify the prognostic factors of disease-specific survival (DSS) for RGC. Methods: We retrospectively collected data from the Surveillance, Epidemiology, and End Results (SEER) database among patients who underwent GC surgery in 1988-2020. Propensity score matching (PSM) was conducted to balance baseline characteristics. Kaplan-Meier (KM) survival analysis was performed to compare their overall survival (OS) and DSS. Multivariable Cox analyses were performed to identify the independent prognostic factors of DSS for post-GC RGC by estimating hazard ratios (HRs) with 95% confidence intervals (CIs). Results: There were 76 patients with RGC and 32,763 patients with OPGC included and analyzed. After balancing the baseline characteristics by PSM, no significant difference existed between OPGC and RGC groups in both OS (P=0.65) and DSS (P=0.28). Fixed-time analyses also showed no difference between the two groups for the 5-year (60.0%, RGC vs. 53.3%, OPGC, P=0.38) and 10-year DSS (56.7%, RGC vs. 48.3%, OPGC, P=0.34). Multivariable analysis revealed that area of lower income ($75,000+ vs. <$55,000, HR =0.21, 95% CI: 0.05-0.89, P=0.03), cardiac tumor [middle vs. cardia, HR =0.16, 95% CI: 0.03-0.77, P=0.02; distal vs. cardia, HR =0.10, 95% CI: 0.02-0.58, P=0.01; not otherwise specified (NOS) vs. cardia, HR =0.11, 95% CI: 0.03-0.51, P=0.004], deeper invasion (T3-4 vs. Tis-2, HR =5.19, 95% CI: 1.21-22.15, P=0.03), higher grade (G3 vs. G1-2, HR =7.35, 95% CI: 1.41-38.48, P=0.02) and not receiving chemotherapy (yes vs. no/unknown, HR =0.16, 95% CI: 0.04-0.60, P=0.007) were independent risk factors for postsurgical DSS in patients with post-GC RGC. Conclusions: The prognosis of post-GC RGC was comparable to that of OPGC following surgical resection. The independent prognostic factors for RGC are similar to those established for OPGC. Our findings suggest that RGC following first GC might be the same entity to OPGC and curative resection should be considered in selected patients.

Extraction Effects on Roselle Functionalities: Antioxidant, Antiglycation, and Antibacterial Capacities.

This study investigated the effects of certain roselle (Hibiscus sabdariffa Linnaeus) extraction methods on various functional properties, including the antioxidant and antiglycation capacities and bacterial growth inhibition. Roselle anthocyanins were extracted using water and ethanol solvents at different temperatures and concentrations. The results revealed that the extraction rate increased with higher temperatures and ethanol concentrations (p < 0.05). Ethanol extracts exhibited higher total organic acid and total anthocyanin contents compared to water extracts, while water extracts showed higher total saccharide, total polyphenol, and total flavonoid contents (p < 0.05). Furthermore, the water extracts demonstrated superior Trolox equivalent antioxidant capacity (TEAC) values, while the ethanol extracts exhibited better 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging ability, antiglycation capacity, and bacterial growth inhibition. A Pearson correlation analysis revealed strong associations between specific components and functional properties, such as a positive correlation between the total anthocyanin content and antiglycation capacity (R2 = 0.9862). A principal component analysis and agglomerative hierarchical clustering highlighted distinct clusters of water and ethanol extracts, indicating solvent-dependent variations in functional properties. This study assessed roselle extraction models for antioxidant, antiglycation, and antibacterial activities, which could be used for the development of functional alcoholic or non-alcoholic beverages.

Fungal Abscess of Anterior Nasal Septum Complicating Maxillary Sinus Fungal Ball Rhinosinusitis Caused by Aspergillus flavus: Case Report and Review of Literature.

Anterior nasal septum abscess is not a rare clinical disease entity. In terms of the etiologies of the disease, bacteria are obviously more common than fungi. Fungal culture and pathological examination are essential for diagnosis of a fungal abscess of the anterior nasal septum and the basis of prescription of antifungal agents. We report a 57-year-old male patient who came to our outpatient clinic due to refractory nasal congestion for 3 weeks despite receiving treatments by a local medical doctor. Radical surgery with postoperative adjuvant radiotherapy for the right buccal cancer was carried out 14 years ago. The patient has diabetes mellitus and the blood sugar level has been well controlled by oral hypoglycemic agents over the past several years. Computed tomography revealed an abscess in the anterior septum along with rhinosinusitis. Incision and drainage of the nasal septum abscess and functional endoscopic sinus surgery were carried out. Fungal culture and pathological examination confirmed a fungal abscess in the anterior nasal septum and fungal ball rhinosinusitis. Antibiotics and an antifungal agent were given, and the postoperative course was uneventful. A dialectical argument was made regarding the causal relationship between the fungal abscess of the anterior nasal septum and maxillary fungal ball sinusitis. A literature review of the previous case reports was carried out to elucidate the immune status of patients of this disease. In order to reach a rapid establishment of a fungal abscess of the anterior nasal septum, clinicians should keep this disease in mind and remain vigilant. An immuno-compromised status is more commonly found in patients with fungal abscess of the anterior nasal septum and is another important characteristic of this disease. Prompt diagnosis and effective treatment are equally important in patients with lower immune status of this kind, and the latter is based on the former.

Stimuli-Responsive mRNA Vaccines to Induce Robust CD8+ T Cell Response via ROS-Mediated Innate Immunity Boosting.

The messenger RNA (mRNA) vaccines hold great significance in contagion prevention and cancer immunotherapy. However, safely and effectively harnessing innate immunity to stimulate robust and durable adaptive immune protection is crucial, yet challenging. In this study, we synthesized a library of stimuli-responsive bivalent ionizable lipids (srBiv iLPs) with smart molecular blocks responsive to esterase, H2O2, cytochrome P450, alkaline phosphatase, nitroreductase, or glutathione (GSH), aiming to leverage physiological cues to trigger fast lipid degradation, promote mRNA translation, and induce robust antitumor immunity via reactive oxygen species (ROS)-mediated boosting. After subcutaneous immunization, esterase-responsive vaccine (eBiv-mVac) was rapidly internalized and transported into the draining lymph nodes. It then underwent fast decaging and self-immolative degradation in esterase-rich antigen-presenting cells, releasing sufficient mRNA for antigen translation and massive reactive quinone methides to elevate ROS levels. This resulted in broad activation of innate immunity to boost T cell response, prompting a large number of primed antigen-specific CD8+ T cells to circulate and infiltrate into tumors (>1000-fold versus unvaccinated control), thereby orchestrating innate and adaptive immunity to control tumor growth. Moreover, by further combining our vaccination strategy with immune checkpoint blockade, we demonstrated a synergism that significantly amplified the magnitude and function of antigen-specific CD8+ T cells. This, in turn, caused potent systemic antitumor efficacy and prolonged survival with high complete response rate in xenograft and metastasis models. Overall, our generalized stimuli-responsive mRNA delivery platform promises a paradigm shift in the design of potent vaccines for cancer immunotherapy, as well as effective and precise carriers for gene editing, protein replacement, and cell engineering.

Reduced-port robotic pancreaticoduodenectomy with optimized surgical field deployment: early results of single-site plus-two ports method.

BACKGROUND: The adoption of Robotic Pancreaticoduodenectomy (RPD) is increasing globally. Meanwhile, reduced-port RPD (RPRPD) remains uncommon, requiring robot-specific techniques not possible with laparoscopy. We introduce a unique RPRPD technique optimizing surgical field exposure. METHODS: Our RPRPD utilizes a single-site plus-two ports technique, facilitated by a single-port platform through a 5-cm incision. The configuration of robotic arms (arm1, arm2, arm3, and arm4) were strategically designed for optimal procedural efficiency, with the arms2 and arm3, alongside the assistant trocar, mounted on the single-port platform, while the arms1 and arm4 were positioned laterally across the abdomen. Drainage was established via channels created at the arm1 and arm4 insertion sites. A "gooseneck traction" was principally employed with the robotic instrument to prop up the specimen rather than grasp, improving the surgical field's visibility and access. Clinical outcomes of patients who underwent RPRPD performed between August 2020 and September 2023 by a single surgeon across two centers in Taiwan and Japan were reviewed. RESULTS: Fifty patients underwent RPRPD using the single-site plus-two ports technique. The gooseneck traction technique enabled goodsurgical field deployment and allowed for unrestricted movement of robotic arms with no collisions with the assistant instruments. The median operative time was 351 min (250-488 min), including 271 min (219-422 min) of console time and three minutes (2-10 min) of docking time. The median estimated blood loss was 80 mL (1-872 mL). All RPRPD procedures were successfully performed without the need for conversion to open surgery. Postoperative major morbidity (i.e., Clavien-Dindo grade ≥ IIIa) was observed in 6 (12%) patients and median postoperative hospital stay was 13 days. CONCLUSIONS: The single-site plus-two ports RPRPD with the gooseneck traction proves to be a safe, feasible option, facilitating surgical field visibility and robotic arm maneuverability.

Notopterygium Incisum Extract Promotes Apoptosis by Preventing the Degradation of BIM in Colorectal Cancer.

OBJECTIVE: Colorectal cancer (CRC), a prevalent malignancy worldwide, has prompted extensive research into anticancer drugs. Traditional Chinese medicinal materials offer promising avenues for cancer management due to their diverse pharmacological activities. This study investigated the effects of Notopterygium incisum, a traditional Chinese medicine named Qianghuo (QH), on CRC cells and the underlying mechanism. METHODS: The sulforhodamine B assay and colony formation assay were employed to assess the effect of QH extract on the proliferation of CRC cell lines HCT116 and Caco-2. Propidium iodide (PI) staining was utilized to detect cell cycle progression, and PE Annexin V staining to detect apoptosis. Western blotting was conducted to examine the levels of apoptotic proteins, including B-cell lymphoma 2-interacting mediator of cell death (BIM), B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (BAX) and cleaved caspase-3, as well as BIM stability after treatment with the protein synthesis inhibitor cycloheximide. The expression of BAX was suppressed using lentivirus-mediated shRNA to validate the involvement of the BIM/BAX axis in QH-induced apoptosis. The in vivo effects of QH extract on tumor growth were observed using a xenograft model. Lastly, APCMin+ mice were used to study the effects of QH extract on primary intestinal tumors. RESULTS: QH extract exhibited significant in vitro anti-CRC activities evidenced by the inhibition of cell proliferation, perturbation of cell cycle progression, and induction of apoptosis. Mechanistically, QH extract significantly increased the stability of BIM proteins, which undergo rapid degradation under unstressed conditions. Knockdown of BAX, the downstream effector of BIM, significantly rescued QH-induced apoptosis. Furthermore, the in vitro effect of QH extract was recapitulated in vivo. QH extract significantly inhibited the tumor growth of HCT116 xenografts in nude mice and decreased the number of intestinal polyps in the APCMin+ mice. CONCLUSION: QH extract promotes the apoptosis of CRC cells by preventing the degradation of BIM.

Periodontitis is an immune-related adverse event associated with immune checkpoint inhibitors: A multi-center cohort study.

Immune checkpoint inhibitors (ICIs) cause immune-related adverse events (irAEs) across various organ systems including oral health complications such as dry mouth and stomatitis. In this study, we aimed to determine the risk of periodontitis among patients on immune checkpoint inhibitors (ICIs) and to test the associations between ICI-associated periodontitis and other immune-related adverse events (irAEs). We performed a retrospective cohort study involving adult cancer patients between January 2010 and November 2021. Patients on an ICI were propensity score-matched to patients not on an ICI. The primary outcome was the occurrence of periodontitis. ICIs included programmed cell death 1 (PD-1) inhibitors programmed cell death ligand 1 (PD-L1) inhibitors, and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors. The risk of periodontitis following ICI use was derived through a Cox proportional hazard model and Kaplan-Meier survival analysis. Overall, 868 patients on an ICI were matched to patients not on an ICI. Among the ICI cohort, 41 (4.7 %) patients developed periodontitis. The incidence rate of periodontitis was significantly higher in patients on an ICI than in patients not on an ICI (55.3 vs 25.8 per 100 patient-years, incidence rate ratio = 2.14, 95 % CI = 1.38-3.33). Both the use of PD-L1 inhibitors (multivariate HR = 2.5, 95%CI = 1.3-4.7) and PD-1 inhibitors (multivariate HR = 2.0, 95%CI = 1.2-3.2) were associated with the risk of periodontitis. The presence of immune-related periodontitis was associated with better overall survival (not reached vs 17 months, log-rank p-value<0.001), progression-free survival (14.9 vs 5.6 months, log-rank p-value = 0.01), and other concomitant immune-related cutaneous adverse events. In conclusion, ICI was associated with an increased risk of periodontitis. Immune-related periodontitis as an irAE was associated with better cancer survival and concomitant cutaneous irAEs.

Loss of plasma fibrinogen contributes to platelet hyporeactivity in rats with septic shock.

INTRODUCTION: Dysregulated host response to infection causes life-threatening organ dysfunction. Excessive inflammation and abnormal blood coagulation can lead to disseminated intravascular coagulation (DIC) and multiple-organ failure in the late sepsis stages. Platelet function impairment in sepsis contributes to bleeding, secondary infection, and tissue injury. Platelet transfusion is considered in patients with sepsis with DIC and bleeding; however, its benefits are limited and of low quality. Fibrinogen plays a crucial role in platelet function, and establishing a fibrin network binds to activated integrin αIIbß3 and promotes outside-in signaling that amplifies platelet functions. However, the role of fibrinogen in sepsis-induced platelet dysfunction remains unclear. MATERIALS AND METHODS: We evaluated the effects of fibrinogen on platelet hyporeactivity during septic shock in adult male Wistar rats using lipopolysaccharide (LPS) injection and cecal ligation and puncture (CLP) surgery. Changes in the hemodynamic, biochemical, and coagulation parameters were examined. Platelet activation and aggregation were measured using whole-blood assay, 96-well plate-based aggregometry, and light-transmission aggregometry. Additionally, platelet adhesion, spreading, and fibrin clot retraction were evaluated. RESULTS: Rats with LPS- and CLP-induced sepsis displayed considerable decreases in plasma fibrinogen levels and platelet aggregation, adhesion, spreading, and clot retraction. The aggregation of platelets obtained from rats with sepsis was markedly augmented by fibrinogen supplementation. Additionally, fibrinogen administration improved platelet adhesion, spreading, and clot retraction in rats with sepsis. CONCLUSIONS: Fibrinogen supplementation could serve as a potential therapeutic intervention for alleviating platelet hyporeactivity in patients with sepsis and bleeding.

Prognostic utility of the geriatric nutritional risk index for head and neck cancer: Systematic review and meta-analysis.

We conducted a systematic review of the literature to assess the potential prognostic utility of geriatric nutritional risk index (GNRI) for head and neck cancer (HNC). We selected studies and extracted data after searching the Cochrane Library, EMBASE, and PubMed databases. The associations between GNRI and survival outcomes were explored by calculating hazard ratios (HRs) and 95% confidence intervals (CIs) through a random-effects meta-analysis. We included 11 studies that involved 2887 patients with HNC. The combined HR demonstrated significant associations of low GNRI with unfavorable progression-free survival (HR = 1.87, 95% CI = 1.32-2.65, p < 0.001) and overall survival (HR = 3.04, 95% CI = 2.30-4.03, p < 0.001). The association between the GNRI and overall survival persisted across various subgroups. The GNRI could serve as a valuable prognostic biomarker for patients with HNC. Low GNRI scores are significantly associated with unfavorable survival outcomes.

[Clinical Features and Prognosis of Patients with CD5+ Diffuse Large B-Cell Lymphoma].

OBJECTIVE: To analyze the clinical characteristics and prognosis of patients with CD5+ diffuse large B-cell lymphoma (DLBCL). METHODS: The clinical data of 161 newly treated DLBCL patients in Gansu Provincial Hospital from January 2013 to January 2020 were retrospectively analyzed. According to CD5 expression, the patients were divided into CD5+ group and CD5- group. The clinical characteristics and prognosis of the two groups were statistically analyzed. RESULTS: The median age of patients in CD5+ group was 62 years, which was higher than 56 years in CD5- group (P =0.048). The proportion of women in CD5+ group was 62.96%, which was significantly higher than 41.79% in CD5- group (P =0.043). The proportion of patients with IPI score > 2 in CD5+ group was 62.96%, which was higher than 40.30% in CD5- group (P =0.031). Survival analysis showed that the median overall survival and progression-free survival time of patients in CD5+ group were 27(3-77) and 31(3-76) months, respectively, which were both shorter than 30(5-84) and 32.5(4-83) months in CD5- group (P =0.047, P =0.026). Univariate analysis showed that advanced age, positive CD5 expression, triple or double hit at initial diagnosis, high IPI score and no use of rituximab during chemotherapy were risk factors for the prognosis of DLBCL patients. Further Cox multivariate regression analysis showed that these factors were also independent risk factors except for advanced age. CONCLUSION: CD5+ DLBCL patients have a worse prognosis than CD5- DLBCL patients. Such patients are more common in females, with advanced age and high IPI score, which is a special subtype of DLBCL.

Prognostic importance of modified geriatric nutritional risk index in oral cavity squamous cell carcinoma.

We probed the associations of preoperative modified geriatric nutritional risk index (mGNRI) values with prognosis in patients receiving surgery for oral cavity squamous cell carcinoma (OCSCC). This retrospective study analyzed the clinical data of 333 patients with OCSCC and undergoing surgery between 2008 and 2017. The preoperative mGNRI was calculated using the following formula: (14.89/C-reactive protein level) + 41.7 × (actual body weight/ideal body weight). We executed receiver operating characteristic curve analyses to derive the optimal mGNRI cutoff and employed Kaplan-Meier survival curves and Cox proportional hazard model to probe the associations of the mGNRI with overall survival (OS) and disease-free survival (DFS). The optimal mGNRI cutoff was derived to be 73.3. We noted the 5-year OS and DFS rates to be significantly higher in the high-mGNRI group than in the low-mGNRI group (both p < 0.001). A preoperative mGNRI below 73.3 was independently associated with unfavorable DFS and OS. A mGNRI-based nomogram was constructed to provide accurate OS predictions (concordance index, 0.781). Hence, preoperative mGNRI is a valuable and cost-effective prognostic biomarker in patients with OCSCC. Our nomogram facilitates the practical use of mGNRI and offers individualized predictions of OS.

In vivo selection in non-human primates identifies AAV capsids for on-target CSF delivery to spinal cord.

Systemic administration of adeno-associated virus (AAV) vectors for spinal cord gene therapy has challenges including toxicity at high doses and pre-existing immunity that reduces efficacy. Intrathecal (IT) delivery of AAV vectors into cerebral spinal fluid can avoid many issues, although distribution of the vector throughout the spinal cord is limited, and vector entry to the periphery sometimes initiates hepatotoxicity. Here we performed biopanning in non-human primates (NHPs) with an IT injected AAV9 peptide display library. We identified top candidates by sequencing inserts of AAV DNA isolated from whole tissue, nuclei, or nuclei from transgene-expressing cells. These barcoded candidates were pooled with AAV9 and compared for biodistribution and transgene expression in spinal cord and liver of IT injected NHPs. Most candidates displayed increased retention in spinal cord compared with AAV9. Greater spread from the lumbar to the thoracic and cervical regions was observed for several capsids. Furthermore, several capsids displayed decreased biodistribution to the liver compared with AAV9, providing a high on-target/low off-target biodistribution. Finally, we tested top candidates in human spinal cord organoids and found them to outperform AAV9 in efficiency of transgene expression in neurons and astrocytes. These capsids have potential to serve as leading-edge delivery vehicles for spinal cord-directed gene therapies.

Parsing patterns: Emerging roles of tissue self-organization in health and disease.

Patterned morphologies, such as segments, spirals, stripes, and spots, frequently emerge during embryogenesis through self-organized coordination between cells. Yet, complex patterns also emerge in adults, suggesting that the capacity for spontaneous self-organization is a ubiquitous property of biological tissues. We review current knowledge on the principles and mechanisms of self-organized patterning in embryonic tissues and explore how these principles and mechanisms apply to adult tissues that exhibit features of patterning. We discuss how and why spontaneous pattern generation is integral to homeostasis and healing of tissues, illustrating it with examples from regenerative biology. We examine how aberrant self-organization underlies diverse pathological states, including inflammatory skin disorders and tumors. Lastly, we posit that based on such blueprints, targeted engineering of pattern-driving molecular circuits can be leveraged for synthetic biology and the generation of organoids with intricate patterns.

Marine Prostanoids with Cytotoxic Activity from Octocoral Clavularia spp.

Octocoral of the genus Clavularia is a kind of marine invertebrate possessing abundant cytotoxic secondary metabolites, such as prostanoids and dolabellanes. In our continuous natural product study of C. spp., two previously undescribed prostanoids [clavulone I-15-one (1) and 12-O-deacetylclavulone I (2)] and eleven known analogs (3-13) were identified. The structures of these new compounds were elucidated based on analysis of their 1D and 2D NMR, HRESIMS, and IR data. Additionally, all tested prostanoids (1 and 3-13) showed potent cytotoxic activities against the human oral cancer cell line (Ca9-22). The major compound 3 showed cytotoxic activity against the Ca9-22 cells with the IC50 value of 2.11 ± 0.03 µg/mL, which echoes the cytotoxic effect of the coral extract. In addition, in silico tools were used to predict the possible effects of isolated compounds on human tumor cell lines and nitric oxide production, as well as the pharmacological potentials.