Survival outcomes of conversion surgery for metastatic pancreatic ductal adenocarcinoma after neoadjuvant therapy

Objective:To evaluate the survival outcomes of patients who underwent conversion surgery for metastatic pancreatic ductal adenocarcinoma(mPDAC)after neoadjuvant therapy(NAT)and to identify potential candidates that may benefit from this treat-ment strategy.Background:The role and eligibility population of conversion surgery for mPDAC remains controversial in the era of NAT.Methods:A consecutive cohort of patients diagnosed with mPDAC and treated with NAT followed by conversion surgery be-tween 2019 and 2021 were confirmed from a prospective database maintained by the Department of Pancreatic Hepatobiliary Surgery of Changhai Hospital.In accordance with residual metastases and technical resectability after NAT,patients were classi-fied as the complete pathological response of metastases(ypM0)resection group,residual metastases(ypM1)resection group,and exploration group.Median overall survival(mOS)was calculated using the Kaplan-Meier method,uni-and multivariable cox regression was performed to identify clinicopathological predictors of OS.Results:A total of 244 patients with mPDAC were identified from the prospective database,with 19(7.8%)patients who un-derwent ypM0 resection,22(9.0%)underwent ypM1 resection,and 23(9.4%)underwent explorative laparotomy.The mOS was 32.6 months for ypM0 resected patients,15.1 months for ypM1 resected patients,and 13.4 months for those who underwent explorative laparotomy(P<.001).Univariable and multivariable Cox regression analyses confirmed that ypM0 resection,normal-ization of preoperative CA19-9 levels,and continued adjuvant therapy were independent prognostic factors of conversion surgery for mPDAC after NAT.Subgroup analyses revealed that oligometastases and continued adjuvant therapy were associated with improved prognosis in the ypM1 resection group.Conclusion:In patients with mPDAC who underwent NAT followed by conversion surgery,the complete pathological response of metastases,normalization of preoperative CA19-9 levels,and continued adjuvant therapy were independent risk factors for prognosis.Patients with residual oligometastases after treatment were expected to prolong survival through resection.These patients may benefit from conversion surgery and should be potential candidates for this treatment strategy.

Reticular exploration of uranium-based metal-organic frameworks with hexacarboxylate building units

The rational reticular design of metal-organic frameworks(MOFs)from building units of known geometries is essential for enriching the diversity of MOF structures.Unexpected and intriguing structures,however,can also arise from subtle changes in the rigidity/length of organic linkers and/or synthetic conditions.Herein,we report three uranium-based MOF structures—i.e.,NU-135X(X=0,1,2)—synthesized from trigonal planar uranyl nodes and triptycene-based hexacarboxylate ligands with variable arm lengths.A new chiral 3,6-connected nuc net was observed in NU-1350,while the extended versions of the ligand led to 3-fold catenated MOFs(NU-1351 and NU-1352)with rare 3,6-connected cml-c3 nets.The differences in the topology of NU-1350 and NU-1351/NU-1352 could be attributed to the slight distortions of the shorter linker in the former from the ideal trigonal prism geometry to an octahedral geometry when coordinated to the trigonal planar uranyl nodes.

Hydrogen-Bonded Organic Frameworks:A Rising Class of Porous Molecular Materials

CONSPECTUS:Hydrogen-bonded organic frameworks(HOFs)are a class of porous molecular materials that rely on the assembly of organic building blocks by means of hydrogen-bonding interactions to form two-dimensional(2D)and three-dimensional(3D)crystalline networks.The reversible nature of the hydrogenbond formation endows HOFs with the attributes of solution processability and simple regeneration.High-quality single crystals of HOFs can be grown easily for unambiguous superstructure determination by single-crystal X-ray diffraction,which is crucial for the elucidation of superstructure−property relationships.During the past decade,considerable progress has been achieved in realizing stable HOFs with permanent porosities by focusing on the design of molecular building blocks in order to introduce rigidity,auxiliary[π···π]interactions,and interpenetration of their frameworks to sustain the extended networks.The applications of HOFs are far-reaching,spanning catalysis,energy,and biomedical products as well as the storage and separation of fine chemicals.In this Account,we,first of all,provide an overview of the chronological development of HOFs,starting from the seminal work by Marsh and Duchamp in 1969 on the crystal superstructure of the hydrogen-bonded networks of trimesic acid.We identify the development of novel hydrogen-bonding motifs such as diaminotriazine(DTA),the introduction of the concept of molecular tectonics,and the establishment of permanent porosity in HOFs as being some of the milestones,which incentivized the current burgeoning research endeavors on developing HOFs as multifunctional materials.This Account is focused primarily on surveying the strategies for constructing porous 3D HOFs based on organic building blocks with peripheral carboxyl groups.These strategies are presented in the following categories:(1)the polycatenation of 2D networks by trigonal building blocks to form global 3D frameworks,(2)the utilization of building blocks with 3D geometriestetrahedral and trigonal prismaticthat are predisposed to form 3D networks,and(3)the docking by shape-fitting of geometrically labile building blocks.We emphasize how the molecular geometry of the building blocks plays an important role in modulating the superstructures of extended frameworks so as to address specific applications.Recognizing that the in silico design of HOFs is the ultimate goal of researchers in this field,we also discuss the recent advances in superstructure prediction that lead to the formation of porous supramolecular crystals and assess the complications in implementing computational methods for HOFs with complex superstructures.We hope this Account will inspire the development of new supramolecular designs and creative approaches to crystal engineering that aid and abet the assembly of multifunctional HOFs with customizable properties.