Tumor burden score as a prognostic factor in patients with intermediate and locally advanced hepatocellular carcinoma undergoing liver resection: an attempt to extend resectability criteria.

BACKGROUND: Surgery is currently recommended as a curative treatment option for hepatocellular carcinomas (HCC) belonging to Barcelona Clinic Liver Cancer (BCLC) stage A only. This study aims to classify various BCLC groups as per Tumor Burden Score (TBS) in an attempt to identify patients who could benefit from resection. MATERIALS AND METHODS: A retrospective analysis of a prospectively maintained database of all patients operated for HCC between January 2010 and July 2022 was performed. TBS was defined as, TBS2 = (maximum tumor diameter)2 + (number of tumors)2. RESULTS: Two hundred and ninety-one patients who underwent resection were staged as per the latest BCLC (A = 219, B = 45, C = 27) staging. Patients were segregated into low (<7.3) and high (>7.3) TBS. With a median follow-up of 36.2 months, the median OS for stages, A and B in the low TBS group was 107.4 and 42.7 months respectively. Median OS was not reached for patients in the BCLC C stage. In patients with high TBS, the median OS for BCLC A, B and C was 42.3, 25.72, and 16.9 months respectively. CONCLUSION: TBS is a significant factor influencing survival in patients of HCC. TBS can be used to stratify patients in BCLC B and C stages and help select patients who would benefit from surgical resection to achieve good long-term survival with acceptable morbidity.

Standardizing Surgical Management of Retroperitoneal Sarcomas: Dawn of a New Surgical Subspeciality in India.

BACKGROUND: Retroperitoneal sarcomas are a complex and heterogenous group of tumors. An approach to these tumors should be guided by a clear understanding of the disease biology and anatomical principles, which mandates a dedicated multidisciplinary team approach at all steps of management. We present our experience of evolution as a high-volume sarcoma center with a dedicated multidisciplinary tumor board (the RP clinic) with consequent standardization of surgeries and management protocols. METHODS: A retrospective analysis of a prospectively maintained database for patients undergoing surgery from January 2011 to June 2023 was performed. Data were divided into the pre-clinic era (2011-2017) and post-clinic era (2018-2023). Survival curves were obtained using the Kaplan-Meier method, and the Chi-square test was used to test significance for categorical variables. Time trends were analyzed using the one-way analysis of variance (ANOVA) test. A p value ≤ 0.05 was considered significant. RESULTS: Overall, 254 patients were operated during this period; 36.6% of patients underwent surgeries in the pre-RP clinic era (6 years) and 63.3% in the post-RP clinic era (4.5 years). There was a statistically significant increase in the number of cases being operated per year, from an average of 16.3 in the pre-clinic era to 42.4 in the post-RP clinic era (p = 0.001). The post-RP clinic era also showed a significant increase in compartment and multivisceral resections (49% vs. 18.2%; p = 0.0001). CONCLUSIONS: Establishment of a dedicated multidisciplinary tumor board (RP clinic) resulted in standardization of management protocols, resulting in optimal oncological and surgical outcomes.

Outcomes of Robotic Surgery in a Single-institution, High-volume Hepatobiliary Oncology Unit.

Hepatobiliary surgery has traditionally been performed via an open approach. With the advent of robotic surgery, the minimal access approach in hepatobiliary oncology has gained impetus due to its technical superiority and favorable learning curve over laparoscopy. We present our experience with the Da Vinci Xi system in hepatobiliary oncology. This is a retrospective study from a prospectively maintained database. All patients who underwent surgery between June 2015 and July 2023 for suspected gallbladder cancer and primary or metastatic liver tumors were included. After excluding all inoperables and conversions, a total of 92 patients were included for analysis. There was a conversion rate of 15.6% (17 of 109 patients). Sixty-four (69.6%) patients underwent surgery for gallbladder-related pathologies that included 39 (60.9%) radical cholecystectomies, 24 (37.5%) simple cholecystectomies, and 1 (0.01%) revision cholecystectomy. Twenty-eight patients underwent surgeries for primary or metastatic liver tumors, which included 25 (92.9%) minor and 2 (7.1%) major hepatectomies. Significant morbidity (Clavien-Dindo grade III or more) was seen in 8 (8.6%). There was no postoperative mortality. In the group with gallbladder cancer, the median lymph nodal yield was 7 (2-22) in patients who underwent lymph nodal dissection. The median follow-up was 63.9 (0.49-100.67) (IQR = 37.76) months. The 5-year OS and DFS were 76.4 and 71.3%, respectively. Robotic hepatobiliary surgery is feasible and can be performed safely after adequate training. Patient selection is of utmost importance and is the key to establishing a robust robotic hepatobiliary oncosurgery program.

Role of Intraoperative Frozen Section Assessment of Proximal Bile Duct Margins and the Impact of Additional Re-Resection in Perihilar Cholangiocarcinomas.

Intraoperative frozen section (FS) analysis to assess the bile duct margin status is commonly used to assess the completeness of resection during surgery for perihilar cholangiocarcinoma (pCCA) resection. However, the impact of additional re-section on the long-term outcome after obtaining an initial positive margin remains unclear. Patients diagnosed as pCCA on preoperative imaging and subjected to curative intent surgery from May 2013 to June 2021 with a minimum follow-up of 2 years were included. Intraoperative FS analysis of the proximal bile duct margin was performed in all patients. A positive margin was defined by the presence of invasive cancer. Out of the 62 patients with a preoperative diagnosis of pCCA on imaging, 35 patients were included for final analyses after excluding patients with inoperable disease (on staging laparoscopy or local exploration) and other/benign pathology on the final histopathology report. Out of the 35 patients, patients with postoperative 90-day mortality were excluded from the final survival analysis. FS analysis revealed an initial positive margin in 10 (28.5%) patients. Among 10 patients who underwent re-resection to achieve negative proximal margins, only 5 patients achieved a negative margin (secondary R0). An initial positive margin was associated with poor long-term outcomes. Median disease-free survival (DFS) and overall survival (OS) were 16 and 19.6 months for patients with an initial positive margin, but 36 and 58.2 months for patients with an initial negative margin, respectively (p = 0.012). The median DFS and OS were significantly lower for those with secondary R0 as compared to primary R0 (16 vs. 36 months for DFS, p = 0.117 and 19.6 vs. 58.2 months for OS, p = 0.027, respectively). An intraoperative FS positive proximal hepatic duct margin dictates poor long-term outcomes for patients with resectable pCCA. Additional resection has a questionable benefit on survival, when a secondary negative margin is achieved.

Green Synthesis of Zinc Oxide Nanoparticles Using Ananas comosus Extract: Preparation, Characterization, and Antimicrobial Efficacy.

Background This study aimed to environmentally synthesize zinc oxide nanoparticles (ZnO-NPs) using Ananas comosus (AC) extract and evaluated their antimicrobial efficacy against Staphylococcus aureus, Streptococcus mutans, and Enterococcus faecalis. Methodology AC extract was combined with a zinc sulfate solution to synthesize ZnO-NPs. The NPs were characterized using UV-visible spectroscopy, Fourier transform infrared (FTIR) analysis, scanning electron microscopy (SEM), and energy-dispersive electron microscopy (EDX). Antimicrobial activity was assessed using the agar disc diffusion method against S. aureus, S. mutans, and E. faecalis. Results Green synthesis of ZnO-NPs with AC extract yielded NPs of different sizes and shapes. SEM analysis showed circular and conical NPs measuring up to 10 nm. EDX analysis confirmed the presence of zinc (Zn) and oxygen (O) particles. UV-visible spectroscopy indicated ZnO-NP formation with a peak at 290 nm. These NPs exhibited strong antimicrobial activity against S. aureus, with larger inhibition zones at higher concentrations, i.e., 15 mm at 100 µL. Whereas they showed low activity of 12 mm at 100 µL against S. mutans and showed no activity against E. faecalis. Conclusions Environmentally friendly synthesis of ZnO-NPs using AC extract provides an effective method for NP production. It exhibits strong antimicrobial activity against S. aureus, indicating the potential for targeted antimicrobial solutions in addressing associated infections.

Suspension culture on microcarriers and as aggregates enables expansion and differentiation of pluripotent stem cells (PSCs).

BACKGROUND AIMS: Human pluripotent stem cells (PSCs) hold a great promise for promoting regenerative medical therapies due to their ability to generate multiple mature cell types and for their high expansion potential. However, cell therapies require large numbers of cells to achieve desired therapeutic effects, and traditional two-dimensional static culture methods cannot meet the required production demand for cellular therapies. One solution to this problem is scaling up expansion of PSCs in bioreactors using culture strategies such as growing cells on microcarriers or as aggregates in suspension culture. METHODS: In this study, we directly compared PSC expansion and quality parameters in microcarrier- and aggregate-cultures grown in single-use vertical-wheel bioreactors. RESULTS: We showed comparable expansion of cells on microcarriers and as aggregates by day 6 with a cell density reaching 2.2 × 106 cells/mL and 1.8 × 106 cells/mL and a fold-expansion of 22- and 18-fold, respectively. PSCs cultured on microcarriers and as aggregates were comparable with parallel two-dimensional cultures and with each other in terms of pluripotency marker expression and retention of other pluripotency characteristics as well as differentiation potential into three germ layers, neural precursor cells and cardiomyocytes. CONCLUSIONS: Our study did not demonstrate a clear advantage between the two three-dimensional methods for the quality parameters assessed. This analysis adds support to the use of bioreactor systems for large scale expansion of PSCs, demonstrating that the cells retain key characteristics of PSCs and differentiation potential in suspension culture.

The effect of surface treatments of tooth on the shear bond strength of direct composite veneers: An in vitro scanning electron microscope study.

Background: The bond strength between tooth structure and restorative materials is critical for the long-term success of dental restorations. This study sought to determine how the shear bond strength (SBS) and type of bond breakdown were affected by the inclusion of sandblasting (SB) as a conditioning step before acid etching (AE). Materials and Methods: A total of 40 extracted human molars were split into two groups at random: intervention (SB followed by AE) and control (AE only). Composite resin cylinders were constructed on the tooth surface following the application of the bonding agent. A universal testing device was used to determine the SBS, and scanning electron microscopy was used to assess the kind of bond failure. Results: In comparison to the control group, the intervention group displayed a significantly higher SBS (P < 0.05). In contrast to the control group, which showed more adhesive failure at the tooth-resin interface, the intervention group also demonstrated a larger percentage of cohesive failure within the composite resin. Conclusion: As an extra conditioning step, AE after SB considerably increased the SBS between tooth structure and composite resin. The fact that the intervention group experienced a higher percentage of cohesive failure shows that this technique could boost the bond's longevity.

Endodontic retreatment efficacy with and without solvents: A systematic review.

Introduction: This systematic review investigates the crucial need for solvent use in root canal retreatment, as it effectively removes filling materials, reduces apical debris extrusion, and alleviates postoperative pain, ultimately enhancing treatment success. The review aims to assess the success rates, compare outcomes, explore benefits and drawbacks, and identify subgroups where solvent use may be more effective during root canal retreatment. Materials and Methods: The search was performed in PubMed Central, Scopus, Cochrane, LILAC, ScienceDirect, Google Search, Web of Science, and manually using the search items alone and in combination by means of PUBMED search builder. The studies were assessed for eligibility according to the eligibility criteria by two independent reviewers. Groups containing solvent with nonsolvent groups and randomized control trials were included and in vitro studies, retrospective studies, and animal studies were excluded from the study. Quality assessment was performed using the risk of bias (RoB) 2.0 tool. Results: Out of the 596 articles obtained, 14 were shortlisted for full-text reading and finally two articles were included in the study. The studies were assessed for quality, and data were extracted in a tabulated form. Overall RoB is low, but due to the lack of homogeneity, meta-analysis could not be conducted. Conclusion: The use of solvent does not cause any significant difference in the postoperative pain levels or analgesic intake for retrieval of gutta-percha in cases of root canal retreatment. Due to the limited number of studies available and the lack of clinician-related outcomes such as time taken to retrieve the gutta-percha, these results should be taken into consideration with caution.

Associations between school-related factors and mental health among transgender and gender diverse youth.

Transgender and gender diverse youth (TGD) report high rates of mental health concerns. However, there is reason to expect that among TGD youth there is variation in mental health experiences related to specific aspects of gender identity. Furthermore, although certain school characteristics are related to improved mental health for sexual minority youth, it is unclear whether the same school characteristics are associated with improved mental health for TGD youth and whether gender identity moderates the associations between school characteristics and mental health. Using baseline data from Project AVANT, a longitudinal study of TGD youth ages 14-18 years in the United States (N = 252), we report on several mental health outcomes (i.e., depression, anxiety, nonsuicidal self-injury, and PTSD), with attention to differences by gender identity. Secondly, we examined associations of three protective school-related factors (i.e., school-connectedness, presence of a Gay-Straight or Gender-Sexuality Alliance [GSA], and state mandated protections for sexual and gender minority students) with TGD youth mental health. TGD youth reported elevated levels of anxious and depressive symptoms, with nonbinary youth assigned female at birth reporting higher mean depressive symptoms relative to transgender females. Among the aggregate sample of TGD youth, 69.9% reported clinically significant anxiety, 57.9% reported clinically significant depression, 56.7% reported nonsuicidal self-injury, and 46.4% met screening criteria for posttraumatic stress disorder. Despite a small effect size, greater school-connectedness was significantly associated with fewer mental health concerns and gender identity moderated the association between school-connectedness and number of anxiety symptoms. Gender identity also moderated the association between presence of a GSA and number of anxious symptoms, depressive symptoms, and clinically significant depression, respectively. No significant associations of state-level protections and mental health outcomes were detected. Findings highlight the importance of improving mental health and fostering GSA-engagement and school-connectedness among TGD youth. Implications for school psychologists are discussed.

At the heart of the interoception network: Influence of the parasubthalamic nucleus on autonomic functions and motivated behaviors.

The parasubthalamic nucleus (PSTN), a small nucleus located on the lateral edge of the posterior hypothalamus, has emerged in recent years as a highly interconnected node within the network of brain regions sensing and regulating autonomic function and homeostatic needs. Furthermore, the strong integration of the PSTN with extended amygdala circuits makes it ideally positioned to serve as an interface between interoception and emotions. While PSTN neurons are mostly glutamatergic, some of them also express neuropeptides that have been associated with stress-related affective and motivational dysfunction, including substance P, corticotropin-releasing factor, and pituitary adenylate-cyclase activating polypeptide. PSTN neurons respond to food ingestion and anorectic signals, as well as to arousing and distressing stimuli. Functional manipulation of defined pathways demonstrated that the PSTN serves as a central hub in multiple physiologically relevant networks and is notably implicated in appetite suppression, conditioned taste aversion, place avoidance, impulsive action, and fear-induced thermoregulation. We also discuss the putative role of the PSTN in interoceptive dysfunction and negative urgency. This review aims to synthesize the burgeoning preclinical literature dedicated to the PSTN and to stimulate interest in further investigating its influence on physiology and behavior.

Outcomes of Transcarotid Versus Trans-Subclavian Transcatheter Aortic Valve Replacement: A Systematic Review and Meta-Analysis.

OBJECTIVES: This study aimed to perform the first meta-analysis of studies comparing transcarotid (TC) and trans-subclavian (TSc) transcatheter aortic valve replacement (TAVR). BACKGROUND: The safety and feasibility of a TC and a TSc approach for performing TAVR in patients with prohibitive femoral anatomy have been well described. The potential advantage of one approach over the other is yet to be ascertained. METHODS: A computerized literature search of key medical databases through September 2020 was performed. Randomized controlled trials (RCTs) and observational studies comparing TC and TSc TAVR with reported 30-day outcomes were considered. The primary endpoint was a composite of all-cause mortality, stroke, life-threatening, and/or major bleeding or major vascular complications. Statistical analysis using random-effects models to report the odds ratio (OR) with 95% confidence interval (CI) was performed. RESULTS: A total of 5 observational studies inclusive of 4164 patients (TC = 1788 and TSc = 2376) met the eligibility criteria. The average age of patients was 81.1 years. There was no difference in the occurrence of the composite endpoint between the groups at 30-days. A statistically insignificant trend towards higher rates of major vascular complications (OR 1.65; 95% CI 0.94-2.89; P = 0.08; I2 = 0%) and the need for permanent pacemaker placement was observed with the TSc approach. CONCLUSIONS: This meta-analysis of studies comparing TC and TSc TAVR showed similar 30-day outcomes between the 2 approaches. A notable trend towards higher rates of major vascular complications and the need for permanent pacemaker placement was observed with the TSc approach.

Cushing syndrome cardiomyopathy: an unusual manifestation of small-cell lung cancer.

Cushing syndrome is a rare cause of dilated cardiomyopathy and heart failure with reduced ejection fraction. Cases describing this association are scarce. We describe a patient presenting with acute heart failure, new cardiomyopathy, refractory hypokalaemia, severe hyperglycaemia, and uncontrolled hypertension who was found to have hypercortisolism secondary to an ectopic adrenocorticotropic hormone-secreting primary lung neoplasm. This case highlights the effects of hypercortisolism on the myocardium. The finding of a non-dilated cardiomyopathy in this case is unique because the majority of previously reported Cushing syndrome cardiomyopathy cases have described left ventricular dilatation or significant left ventricular hypertrophy. In addition, small-cell lung cancer with adrenocorticotropic hormone production causing Cushing syndrome cardiomyopathy is rare.

Treatment of Life-Threatening ACE-Inhibitor-Induced Angioedema.

Incidence of angioedema associated with angiotensin-converting enzyme inhibitors (ACE-I) has been estimated at 0.1%-2.2% of patients receiving treatment. Despite the potential severity of this disease state, standardized treatment is lacking. Traditional pharmacotherapy options include medications that target inflammatory mediators and the angiotensin pathway. However, because ACE-I-induced angioedema is caused by accumulation of bradykinin, these medications fail to target the underlying pathophysiology. Recently, novel therapies that target the kallikrein-bradykinin pathway have been studied. These include icatibant, ecallantide, C1 esterase inhibitors, and fresh-frozen plasma. Recent randomized controlled trials exhibit contradictory results with the use of icatibant. This is a focused review on traditional and novel treatment strategies for ACE-I-induced angioedema.

Elevated end-diastolic wall stress after acute myocardial infarction predicts adverse cardiovascular outcomes and longer hospital length of stay.

BACKGROUND: Acute myocardial infarction (MI) leads to ventricular remodeling in response to oxygen demand. Such changes include left ventricular (LV) dilatation and increased myocardial wall stress. Prior studies showed that wall stress is a vital parameter of cardiac remodeling. However, outcome data are lacking. We aim to investigate wall stress post-MI in relation to biomarkers of cardiac remodeling and cardiovascular outcomes. METHODS: Patients presenting with ST-elevation MI (STEMI) requiring primary percutaneous intervention (PCI) were enrolled prospectively. LVEF and volume-based end-diastolic (EDWS) and end-systolic (ESWS) wall stress were measured from predischarge echocardiograms. Serum samples were collected for measurement of serum biomarkers. We identified 81 patients meeting inclusion criteria (64% men, 36% women) with a mean age of 61. The primary outcome was major adverse cardiovascular events (MACE) defined as 1-year composite endpoint of cardiac mortality, recurrent MI, revascularization, or stroke. Length of hospitalization (LOH) was recorded. RESULTS: Major adverse cardiovascular events-positive patients (n = 12) had significantly higher EDWS levels (15.87 vs 12.33, P = 0.045), and galectin-3 levels (19.07 vs 11.75, P = 0.015), and lower LVEF (40.0% vs 48.4%, P = 0.023) compared to MACE-negative patients. Patients with LOH > 72 hours (n = 33) had significantly higher EDWS, galectin-3, and peak troponin, and lower LVEF compared to patients with LOH < 72 hours. EDWS positively correlated with LOH and galectin-3. EDWS was an independent predictor of MACE by binomial regression analysis. CONCLUSION: End-diastolic walls tress is a potential prognostic tool for risk stratifying STEMI patients, providing an assessment of the functional consequences of myocardial remodeling. It is predictive of MACE independent of LVEF, associated with longer hospitalizations, and correlates with galectin-3, a biomarker of cardiac remodeling.

The Therapeutic Potential of Blocking Galectin-3 Expression in Acute Myocardial Infarction and Mitigating Inflammation of Infarct Region: A Clinical Outcome-Based Translational Study.

INTRODUCTION: Increased galectin-3 is associated with ischemic cardiomyopathy, although its role in early remodeling post-myocardial infarction (MI) has not been fully elucidated. There are no data demonstrating that blocking galectin-3 expression would have an impact on the heart and that its relationship to remodeling is not simply an epiphenomenon. The direct association between galectin-3 and myocardial inflammation, dysfunction, and adverse cardiovascular outcomes post-MI was examined using clinical and translational studies. METHODS: We performed expression analysis of 9753 genes in murine model of acute MI. For galectin-3 loss of function studies, homozygous galectin-3 knock-out (KO) mice were subjected to coronary artery ligation procedure to induce acute MI (MI, N = 6; Sham, N = 6). For clinical validation, serum galectin-3 levels were measured in 96 patients with ST-elevation MI. Echocardiographic and angiographic parameters of myocardial dysfunction and 3-month composite outcome including mortality, recurrent MI, stroke, and heart failure hospitalization were measured. RESULTS: In the infarct regions of murine models, galectin-3 was a robustly expressed gene. Elevated galectin-3 expression strongly correlated with macrophage-mediated genes. Galectin-3 KO mice showed reduced myocardial macrophage infiltration after acute MI. Galectin-3 levels were higher in patients with early systolic dysfunction, and predicted 3-month major adverse cardiovascular events (area under the curve [AUC]: 0.917 ± 0.063; P = .001). CONCLUSIONS: Galectin-3 is directly associated with early myocardial inflammation post-MI and may represent a potential target for therapeutic inhibition.