Higher Postoperative Mortality and Inferior Survival After Right-Sided Liver Resection for Perihilar Cholangiocarcinoma: Left-Sided Resection is Preferred When Possible.

BACKGROUND: A right- or left-sided liver resection can be considered in about half of patients with perihilar cholangiocarcinoma (pCCA), depending on tumor location and vascular involvement. This study compared postoperative mortality and long-term survival of right- versus left-sided liver resections for pCCA. METHODS: Patients who underwent major liver resection for pCCA at 25 Western centers were stratified according to the type of hepatectomy-left, extended left, right, and extended right. The primary outcomes were 90-day mortality and overall survival (OS). RESULTS: Between 2000 and 2022, 1701 patients underwent major liver resection for pCCA. The 90-day mortality was 9% after left-sided and 18% after right-sided liver resection (p < 0.001). The 90-day mortality rates were 8% (44/540) after left, 11% (29/276) after extended left, 17% (51/309) after right, and 19% (108/576) after extended right hepatectomy (p < 0.001). Median OS was 30 months (95% confidence interval [CI] 27-34) after left and 23 months (95% CI 20-25) after right liver resection (p < 0.001), and 33 months (95% CI 28-38), 27 months (95% CI 23-32), 25 months (95% CI 21-30), and 21 months (95% CI 18-24) after left, extended left, right, and extended right hepatectomy, respectively (p < 0.001). A left-sided resection was an independent favorable prognostic factor for both 90-day mortality and OS compared with right-sided resection, with similar results after excluding 90-day fatalities. CONCLUSIONS: A left or extended left hepatectomy is associated with a lower 90-day mortality and superior OS compared with an (extended) right hepatectomy for pCCA. When both a left and right liver resection are feasible, a left-sided liver resection is preferred.

Novel antiarthritic mechanisms of Azelaic acid against CFA-induced arthritis in rats by modulating pro- and anti-inflammatory cytokines network.

An immunologic system attacking the body's own tissues is a hallmark of autoimmune disorders, which encompass a wide range of unique conditions. Numerous essential biologic functions, including the regulation of the immune system, inflammation, cell division, and tissue repair, are carried out by cytokines. Natural compounds are an effective treatment for autoimmune illnesses by modulation of inflammatory cytokines and infiltration of leukocytes into the inflamed tissue. Here, anti-arthritic study was carried out using oral administration of Azelaic acid (AzA) for 28 days with doses (20, 40, and 80 mg/kg) in Complete Freund's Adjuvant (CFA) induced arthritis model. AzA ameliorated the adjuvant-induced arthritis by decreasing arthritic score, paw volume, improved body-weight alterations and serum levels of PGE2, 5-LOX and anti-ccp. AzA showed significant down regulation of NF-κB, COX-II, TNF-α, IL-17, IL-1ß, IL-6, and up regulation of IL4 and IL10. Hemoglobin and RBCs count remarkably increased and ESR, CRP, platelets, WBCs levels markedly reduced in post treatment. In addition, the weakened SOD (superoxide dismutase), Catalase (CAT), Glutathione (GSH) activity and the increased levels of malondialdehyde (MDA) were all reversed by AzA treatment. And showed improved radiographical and histologic alterations in the structure of the joints. Molecular docking studies targeting COX-II, iNOS, TNF-α, 5-LOX, IL4, IL10, IL-6, and IL-17 establish a correlation between theoretical and experimental results. Results showed that AzA inhibit pro-inflammatory cytokines (COX-II, TNF-α, 5-LOX, IL-17, NF-κB, IL-1ß, and IL-6) and increase anti-inflammatory cytokines, which supported the anti-arthritic and immunomodulatory potential of AzA.

Molecular insights of Eucalyptol (1,8-Cineole) as an anti-arthritic agent: in vivo and in silico analysis of IL-17, IL-10, NF-κB, 5-LOX and COX-2.

The monoterpene oxide, Eucalyptol (1,8-Cineole), a primary component of eucalyptus oil, has been evaluated pharmacologically for anti-inflammatory and analgesic activity. Current research aimed to evaluate Eucalyptol's anti-arthritic potential in a Complete Freund's adjuvant induced arthritis that resembles human rheumatoid arthritis. Polyarthritis developed after 0.1 mL CFA injection into the left hind footpad in rats. Oral administration of Eucalyptol at various doses (100, 200 and 400 mg/kg) significantly reduced paw edema, body weight loss, 5-LOX, PGE2 and Anti-CCP levels. Real-time PCR investigation showed significant downregulation of COX-2, TNF-α, NF-κB, IL-17, IL-6, IL-1ß and upregulation of IL-4 and IL-10 in Eucalyptol treated groups. Hemoglobin and RBCs counts significantly increased post-treatment with Eucalyptol while ESR, CRP, WBCs and platelets count significantly decreased. Eucalyptol significantly increased Superoxide Dismutase, Catalase and Glutathione levels compared to CFA-induced arthritic control however, MDA significantly decreased post-treatment. Further, radiographic and histopathological examination of the ankle joints of rodents administered Eucalyptol revealed an improvement in the structure of the joints. Piroxicam was taken as standard. Furthermore, molecular docking findings supported the anti-arthritic efficacy of Eucalyptol exhibited high binding interaction against IL-17, TNF-α, IL-4, IL-10, iNOS NF-κB, 5-LOX, and COX-2. Eucalyptol has reduced the severity of CFA induced arthritis by promoting anti-inflammatory cytokines for example IL-4, IL-10 and by inhibiting pro-inflammatory cytokines such as 5-LOX, COX-2, IL-17, NF-κB, TNF-α, IL-6 and IL-1ß. Therefore, Eucalyptol might be as a potential therapeutic agent because of its pronounced anti-oxidant and anti-arthritic activity.

Roles of Hydrogen Sulfide (H2S) as a Potential Therapeutic Agent in Cardiovascular Diseases: A Narrative Review.

Cardiovascular disease (CVD) stands as one of the leading causes of morbidity and mortality worldwide, and the continued search for novel therapeutics is vital for addressing this global health challenge. Over the past decade, hydrogen sulfide (H2S) has garnered significant attention in the field of medical research, as it has been proven to be a cardioprotective gaseous signaling molecule. It joins nitric oxide and carbon monoxide as endogenously produced gasotransmitters. As for its mechanism, H2S functions through the posttranslational addition of a sulfur group to cysteine residues on target proteins in a process called sulfhydration. As a result, the observed physiological effects of H2S can include vasodilation, anti-apoptosis, anti-inflammation, antioxidant effects, and regulation of ion channels. Various studies have observed the cardioprotective benefits of H2S in diseases such as myocardial infarction, ischemia-reperfusion injury, cardiac remodeling, heart failure, arrhythmia, and atherosclerosis. In this review, we discuss the mechanisms and therapeutic potential of H2S in various CVDs.

The importance of preclinical models in cholangiocarcinoma.

Cholangiocarcinoma (CCA) is an adenocarcinoma of the hepatobiliary system with a grim prognosis. Incidence is rising globally and surgery is currently the only curative treatment, but is only available for patients who are fit and diagnosed in an early-stage of disease progression. Great importance has been placed on developing preclinical models to help further our understanding of CCA and potential treatments to improve therapeutic outcomes. Preclinical models of varying complexity and cost have been established, ranging from more simplistic in vitro 2D CCA cell lines in culture, to more complex in vivo genetically engineered mouse models. Currently there is no single model that faithfully recaptures the complexities of human CCA and the in vivo tumour microenvironment. Instead a multi-model approach should be used when designing preclinical trials to study CCA and potential therapies.

Association Between Cervical Sagittal Alignment and Subaxial Paraspinal Muscle Parameters.

STUDY DESIGN: Retrospective review of prospectively collected data. OBJECTIVE: The authors aim to investigate the association between muscle functional group characteristics and sagittal alignment parameters in patients undergoing anterior cervical discectomy and fusion. SUMMARY OF BACKGROUND DATA: The relationship between the morphology of cervical paraspinal muscles and sagittal alignment is not well understood. MATERIALS AND METHODS: Patients with preoperative cervical magnetic resonance imaging and cervical spine lateral radiographs in standing position who underwent anterior cervical discectomy and fusion between 2015 and 2018 were reviewed. Radiographic alignment parameters included C2 to 7 lordosis, C2 to 7 sagittal vertical axis (SVA), C2 slope, neck tilt, T1 slope, and thoracic inlet angle. Muscles from C3 to C7 were categorized into four functional groups: sternocleidomastoid group, anterior group, posteromedial group, and posterolateral group (PL). A custom-written Matlab software was used to assess the functional cross-sectional area (fCSA) and percent fat infiltration (FI) for all groups. Multivariable linear regression analyses were conducted and adjusted for age, sex, and body mass index. RESULTS: A total of 172 patients were included. Regression analyses demonstrated that a greater C2 to 7 SVA was significantly associated with a greater FI of the anterior group from C3 to C5 and with a higher fCSA of the PL group at C3 to C4, and C6 to 7. A larger C2 slope was significantly correlated with a greater FI of the anterior group at C3 to C4 and a higher fCSA of the PL group from C3 to C5. CONCLUSION: This work proposes new insights into the complex interaction between sagittal alignment and cervical paraspinal muscles by emphasizing the importance of these muscles in sagittal alignment. The authors hypothesize that with cervical degeneration, the stabilizing function of the anterior muscles decreases, which may result in an increase in the compensatory mechanism of the PL muscles. Consequently, there may be a corresponding increase in the C2 to C7 SVA and a larger C2 slope.

Association between severity of the cervical foraminal stenosis and paraspinal muscle parameters in patients undergoing anterior cervical discectomy and fusion.

OBJECTIVE: The cervical multifidus and rotatores muscles are innervated by the posterior rami of the spinal nerves of the corresponding level, and it has been hypothesized that cervical foraminal stenosis (CFS) affecting the spinal nerves results in changes in these muscles. The purpose of this study was to evaluate the relationship between the severity of CFS and fat infiltration (FI) of the multifidus and rotatores muscles. METHODS: Patients who received preoperative cervical MRI, underwent anterior cervical decompression and fusion between 2015 and 2018, and met inclusion and exclusion criteria were included. Multifidus and rotatores muscles were segmented bilaterally from C3 to C7, and the percent FI was measured using custom-written MATLAB software. The severity of the CFS was assessed by the Kim classification. Multivariable linear mixed models were conducted and adjusted for age, sex, BMI, and repeated measures. RESULTS: In total, 149 patients were included. Linear mixed modeling results showed that a more severe CFS at C3-4 was correlated with a greater FI of the multifidus and rotatores muscles at C4 (estimate 0.034, 95% CI 0.003-0.064; p = 0.031), a more severe CFS at C4-5 was correlated with a greater FI of the multifidus and rotatores muscles at C5 (estimate 0.037, 95% CI 0.015-0.057; p < 0.001), a more severe CFS at C5-6 was correlated with a greater FI of the multifidus and rotatores muscles at C6 (estimate 0.041, 95% CI 0.019-0.062; p < 0.001) and C7 (estimate 0.035, 95% CI 0.012-0.058; p = 0.003), and a more severe CFS at C6-7 was correlated with a greater FI of the multifidus and rotatores muscles at C7 (estimate 0.049, 95% CI 0.027-0.071; p < 0.001). CONCLUSIONS: These results demonstrated level- and side-specific correlations between the FI of the multifidus and rotatores muscles and severity of CFS. Given the segmental innervation of the multifidus and rotatores muscles, the authors hypothesize that the observed increased FI could be reflective of changes due to muscle denervation from CFS.

Association Between Severity of Cervical Central Spinal Stenosis and Paraspinal Muscle Parameters in Patients Undergoing Anterior Cervical Discectomy and Fusion.

STUDY DESIGN: Retrospective study. OBJECTIVE: The aim of this study was to evaluate the association between severity and level of cervical central stenosis (CCS) and the fat infiltration (FI) of the cervical multifidus/rotatores (MR) at each subaxial levels. SUMMARY OF BACKGROUND DATA: The relationship between cervical musculature morphology and the severity of CCS is poorly understood. METHODS: Patients with preoperative cervical magnetic resonance imaging (MRI) who underwent anterior cervical discectomy and fusion (ACDF) were reviewed. The cervical MR were segmented from C3 to C7 and the percent FI was measured using a custom-written Matlab software. The severity of the CCS at each subaxial level was assessed using a previously published classification. Grade 3, representing a loss of cerebrospinal fluid space and deformation of the spinal cord > 25%, was set as the reference and compared to the other gradings. Multivariable linear regression analyses were conducted and adjusted for age, sex, and body mass index. RESULTS: 156 consecutive patients were recruited. A spinal cord compression at a certain level was significantly associated with a greater FI of the MR below that level. After adjustment for the above-mentioned confounders, our results showed that spinal cord compression at C3/4 and C4/5 was significantly associated with greater FI of the MR from C3 to C6 and C5 to C7, respectively. A spinal cord compression at C5/6 or C6/7 was significantly associated with greater FI of the MR at C7. CONCLUSION: Our results demonstrated significant correlations between the severity of CCS and a greater FI of the MR. Moreover, significant level-specific correlations were found. A significant increase in FI of the MR at the levels below the stenosis was observed in patients presenting with spinal cord compression. Given the segmental innervation of the MR, the increased FI might be attributed to neurogenic atrophy. LEVEL OF EVIDENCE: 3.

Helicobacter pylori outer membrane protein Q genotypes and their susceptibility to anti-adhesive phytotherapeutic agents / 中西医结合学报

<p><b>OBJECTIVE</b>Helicobacter pylori is a Gram-negative organism. Its outer membrane protein Q (HopQ) mediates host-pathogen interactions; HopQ genotypes 1 and 2 are found associating with gastroduodenal pathologies. The authors measured the anti-adhesion effects of the extracts of Abelmoschus esculentus, Zingiber officinale, Trachyspermum ammi, Glycyrrhiza glabra, Curcuma longa and Capsicum annum against HopQ genotypes and H. pylori cytotoxin-associated gene A (CagA).</p><p><b>METHODS</b>DNA was extracted by polymerase chain reaction of the HopQ genotypes (i.e., type 1, type 2 and CagA) from 115 H. pylori strains. The effect of the extracts from selected dietary ingredients was determined using a gastric adenocarcinoma cell line and a quantitative DNA fragmentation assay. The anti-adhesive effect of these extracts on H. pylori was tested using an anti-adhesion analysis.</p><p><b>RESULTS</b>C. annum, C. longa and A. esculentus showed prominent anti-adhesion effects with resultant values of 17.3% ± 2.9%, 14.6% ± 3.7%, 13.8% ± 3.6%, respectively, against HopQ type 1 and 13.1% ± 1.7%, 12.1% ± 2%, 11.1% ± 1.6%, respectively, against HopQ type 2. C. longa (93%), C. annum (89%) and A. esculentus (75%) had better anti-adhesive activity against H. pylori with HopQ type 1 compared to HopQ type 2 with respective values of 70%, 64% and 51%. Extracts of C. annum (14.7% ± 4.1%), A. esculentus (12.3% ± 4.1%) and Z. officinale (8.4% ± 2.8%) had an anti-adhesion effect against CagA-positive H. pylori strains compared to CagA-negative strains.</p><p><b>CONCLUSION</b>The anti-adhesion properties of the tested phytotherapeutic dietary ingredients were varied with HopQ genotypes. HopQ type 1 was found to be more sensitive to extracts of C. annum, C. longa and A. esculentus compared to the HopQ type 2 genotype.</p>

Antiacanthamoebic properties of natural and marketed honey in Pakistan

Objective To determine antiacanthamoebic activity of natural and marketed honey samples. Methods Natural honey samples were collected directly from the bee hive and marketed honey samples were purchased from the local market in Karachi, Pakistan. Both honey samples were tested for their flavonoid content (quercetin equivalent per gram of the extract) and phenolic content (gallic acid equivalent per gram). Furthermore, their antioxidant activity was determined by measuring 2,2-diphenyl-1-picrylhydrazyl. Using amoebistatic and amoebicidal assays, the effects of honey samples were tested against growth and viability of Acanthamoeba parasites. Results Natural honey exhibited potent amoebistatic and amoebicidal effects, in a concentration-dependent manner. Honey-treated Acanthamoeba castellanii showed loss of acanthopodia, following which amoebae detached, rounded up, reduced in size, decreased in cytoplasmic mass and they were observed floating in the culture medium. Importantly, honey-treated amoebae did not revive when inoculated in fresh growth medium, however, glycerol-treated amoebae exhibited viable trophozoite and active growth. In contrast, marketed honey samples varied in their efficacy against Acanthamoeba castellanii. The proportion of flavonoid, as determined by quercetin measurements and the proportion of phenolic, as determined by gallic acid measurements was higher in natural honey compared with marketed honey. Similarly, the antioxidant activity, as determined by 2,2-diphenyl-1-picrylhydrazyl scavenging activity was higher in natural honey vs. marketed honey. Conclusions This study shows that natural honey has antiacanthamoebic properties and possesses higher flavonoid, phenolic and antioxidant properties compared with the marketed honey. These findings are of concern to the public, health officials, and to the manufacturers regarding production of honey for medical applications.