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Background: Efforts to address US liver transplant (LT) access inequities continue, yet disparities linked to candidate traits persist., Methods: Analyzing national registry data pre- and post-Acuity Circle (AC) policy, our study assessed the impact of low body surface area (BSA) on LT waitlist mortality. The outcomes of LT candidates listed in the pre-AC era (n = 39 227) and post-AC (n = 38 443) were compared for patients with low BSA (22.9% pre-AC and 23.3% post-AC)., Results: Fine-Gray competing risk models highlighted that candidates with low BSA had a lower likelihood of LT both pre-AC (hazard ratio [HR] 0.93; 95% confidence interval [CI], 0.92-0.95) and post-AC (HR 0.96; 95% CI, 0.94-0.98), with minimal improvement in waitlist mortality/dropout risk from pre-AC (HR 1.15; 95% CI, 1.09-1.21) to post-AC (HR 1.13; 95% CI, 1.06-1.19). Findings were mostly reaffirmed by Cox regression models incorporating the trajectory of Model for End-stage Liver Disease (MELD) scores as time-dependent covariates. Regions 3, 5, and 7 showed notable LT waitlist disparities among low BSA patients post-AC policy. Causal mediation analysis revealed that low BSA and the difference between MELD-sodium and MELD 3.0 (MELD_D, as a proxy for the potential impact of the introduction of MELD 3.0) largely explained the sex disparity in AC allocation (percent mediated 90.4)., Conclusions: LT waitlist disparities for female candidates persist, largely mediated by small body size. Although MELD 3.0 may reduce some disparities, further body size adjustments for in allocation models are justified., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: There has been an increase in the elderly patient population seeking care for pancreatic ductal adenocarcinoma (PDAC). This study aimed to delineate the effectiveness of therapeutic options in nonagenarians (aged 90-99 years) diagnosed with resectable PDAC., Methods: This study used the National Cancer Database to identify patients with nonmetastatic PDAC (stage I-III) from 2004 to 2021. The study compared median overall survival (mOS) using Kaplan-Meier curves among 5 treatment categories: surgery, surgery along with chemoradiation, chemotherapy alone, radiotherapy alone, and chemoradiation alone. Cox proportional hazards regression was used in multivariate analyses., Results: Of 459,174 patients, 793 aged ≥ 90 years had nonmetastatic PDAC. Of 793 patients, 245 (30.9 %) underwent chemotherapy alone, 296 (37.3 %) underwent radiotherapy alone, 162 (20.4 %) underwent chemoradiation alone, 58 (7.3 %) underwent curative-intent resection, and 32 (4.0 %) underwent surgery combined with chemoradiation. The mOS estimates in different treatment modalities were 9.5 months (95 % CI, 6.7-14.5) for surgery alone, 19.1 months (95 % CI, 2.4-64.3) for surgery combined with chemoradiation, 8.2 months (95 % CI, 7.2-9.2) for chemotherapy alone, 8.4 months (95 % CI, 7.6-9.6) for radiotherapy alone, and 11.2 months (95 % CI, 8.7-12.9) for chemoradiation alone (P < .001). In multivariate analysis, the odds of survival were better for patients who underwent surgery alone than for those who underwent chemotherapy alone, although the odds of survival did not significantly differ between patients who underwent radiotherapy alone and those who underwent chemoradiation alone. Nonetheless, surgery combined with chemoradiation was associated with decreased mortality risk compared with surgery alone (hazard ratio, 0.46; 95 % CI, 0.25-0.87; P = .02). Operative 30-day mortality rate was 8.8 %, and 90-day mortality rate was 17.8 %., Conclusion: Surgery combined with chemoradiation improved the survival of nonagenarians with PDAC compared with other therapies. However, only 1 in 25 patients received all 3 treatment components. Moreover, our study highlights a very high operative mortality rate in nonagenarians., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2024 Society for Surgery of the Alimentary Tract. Published by Elsevier Inc. All rights reserved.)

Aims: The screening of antimycobacterial benzo[ d ]thiazole-2-carboxamides against ATP-phosphoribosyl transferase (ATP-PRTase) was conducted. Materials & methods: The antitubercular potential of compounds  1 and 2 against ATP-PRTase was assessed through the determination of half maximal effective concentration (EC 50 ) and binding constant (K d ), as well as competitive inhibitory studies and studies of perturbation of secondary structure, molecular modeling and L-histidine complementation assay. Results & conclusion:  Compounds 1n and 2a significantly inhibited ATP-PRTase as evidenced by their EC 50 and K d  values and the perturbation of the secondary structure study. Compound 1n exhibited stronger competitive inhibition toward ATP compared with 2a . The inhibition of the growth of Mycobacterium tuberculosis by targeting the L-histidine biosynthesis pathway and molecular modeling studies further supported the inhibition of ATP-PRTase.

Tuberculosis is the second leading cause of deaths worldwide. The inadequacy of existing drugs to treat TB due to developed resistance and TB-HIV synergism urges for new anti-TB drugs. Seventy-two benzo[d]thiazole-2-carbanilides have been synthesized through CDI-mediated direct coupling of benzo[d]thiazole-2-carboxylic acids with aromatic amines using a three step methodology which includes a green protocol for synthesis of ethyl benzo[d]thiazole-2-carboxylates, precursor of the desired carboxylic acids. The compounds were evaluated in vitro for anti-tubercular activity against M. tuberculosis H 37 Rv (ATCC27294 strain). Thirty-two compounds exhibiting MIC values in the range of 0.78-6.25 μg/mL (1.9-23 μM) were subjected to cell viability test against RAW 264.7 cell lines and thirty compounds were found to be non-toxic (<50% inhibition). The most active compounds with MIC of 0.78 μg/mL (e.g., 4i, 4n, 4s, 4w, 6f, 6h, 6u, 7e, 7h, 7p, 7r and 7w) exhibit therapeutic index of 64. The structure activity relationship of the N-arylbenzo[d]thiazole-2-carboxamides has been established for anti-mycobacterial activity. Molecular docking suggests that the compounds 7w, 4i and 4n bind to the catalytic site of the enzyme ATP Phosphoribosyltransferase (HisG) and might be attributed to their anti-TB potential. These can serve as a new starting point for the development of anti-TB agents with therapeutic potential., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

The benzo[d]thiazol-2-yl(piperazin-1-yl)methanones scaffold has been identified as new anti-mycobacterial chemotypes. Thirty-six structurally diverse benzo[d]thiazole-2-carboxamides have been prepared and subjected to assessment of their potential anti-tubercular activity through in vitro testing against Mycobacterium tuberculosis H37Rv strain and evaluation of cytotoxicity against RAW 264.7 cell lines. Seventeen compounds showed anti-mycobacterial potential having MICs in the low (1-10) μM range. The 5-trifluoromethyl benzo[d]thiazol-2-yl(piperazin-1-yl)methanones emerged to be the most promising resulting in six positive hits (2.35-7.94 μM) and showed low-cytotoxicity (<50% inhibition at 50 μg/mL). The therapeutic index of these hits is 8-64. The quantitative structure activity relationship has been established adopting a statistically reliable CoMFA model showing high prediction (rpred(2)=0.718,rncv(2)=0.995)., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)