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1.
Ann Surg Oncol ; 23(6): 1941-7, 2016 06.
Article in English | MEDLINE | ID: mdl-26842489

ABSTRACT

PURPOSE: Cytoreductive surgery/hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) for peritoneal carcinomatosis is a morbid endeavor. Despite improvement in perioperative management of these patients, there are subsets of patients requiring hospital readmission after discharge. We sought to identify variables associated with readmission rates for CRS/HIPEC. METHODS: We conducted a retrospective review of CRS/HIPEC cases at the University of Cincinnati between 1999 and 2014. Patient-, tumor-, and treatment-specific characteristics were evaluated. The association between patient- and outcome-specific variables for 30- and 90-day readmission were evaluated. RESULTS: Of 215 CRS/HIPEC patients, the 7-, 30-, and 90-day readmission rates were 9.8 % (n = 21), 14.9 % (n = 32), and 21.4 % (n = 46), respectively. The most common reasons for readmission within 90 days included abdominal pain (n = 14), intra-abdominal abscess (n = 9), malnutrition/failure to thrive (n = 8), and bowel obstruction (n = 7). The primary factor associated with readmission at all time points (7, 30, and 90 days) was the presence of an enterocutaneous fistula (p < 0.01). Six patients (2.8 %) had multiple readmissions; 3 of these had ECF. Factors not associated with higher admission rates included sex, age, race, operative blood loss, pancreatectomy or liver resection at the index operation, and postoperative complications of wound infection, line infection, and thromboembolic events. CONCLUSIONS: In patients undergoing CRS/HIPEC, readmission was primarily associated with poor pain control, malnutrition, and infectious complications. Patients with enterocutaneous fistula were also disproportionately readmitted multiple times. These data should inform clinicians about patients at high risk for readmission after CRS/HIPEC and encourage more comprehensive coordination of postdischarge planning and care for specific patient populations.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cytoreduction Surgical Procedures/adverse effects , Hyperthermia, Induced/adverse effects , Neoplasms/therapy , Patient Readmission/statistics & numerical data , Peritoneal Neoplasms/therapy , Postoperative Complications , Adolescent , Adult , Aged , Aged, 80 and over , Chemotherapy, Cancer, Regional Perfusion/adverse effects , Combined Modality Therapy , Female , Follow-Up Studies , Humans , Male , Middle Aged , Neoplasms/pathology , Peritoneal Neoplasms/secondary , Prognosis , Retrospective Studies , Risk Factors , Survival Rate , Young Adult
2.
J Med Chem ; 56(4): 1596-613, 2013 Feb 28.
Article in English | MEDLINE | ID: mdl-23327489

ABSTRACT

Five compounds displaying an unprecedented binding mode of chloroquine to ferrocene through the bridging of the cyclopentadienyl rings were studied alongside their monosubstituted ferrocene analogues and organic fragments. The antiplasmodial activity was evaluated against strains of the malaria parasite (Plasmodium falciparum). While the chloroquine-bridged ferrocenyl derivatives were less active than their five monosubstituted ferrocenyl analogues, they retained activity in the drug-resistant strains. The biological and physical properties were correlated to antiplasmodial activity. Intramolecular hydrogen bonding was associated with increased antiplasmodial action, but it is not the determining factor. Instead, balance between lipophilicity and hydrophilicity had a greater influence. It was found that calculated partition coefficient (log P) values of 4.5-5.0 and topological polar surfaces area (tPSA) values of ∼26.0 Å(2) give the best balance. The particular conformation, compact size, and lipophilicity/hydrophilicity balance observed in the bridged compounds provide them with the structural characteristics needed to escape the mechanisms responsible for resistance.


Subject(s)
Aminoquinolines/chemistry , Antimalarials/chemistry , Chloroquine/analogs & derivatives , Chloroquine/chemistry , Ferrous Compounds/chemistry , Aminoquinolines/chemical synthesis , Aminoquinolines/pharmacology , Antimalarials/chemical synthesis , Antimalarials/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Chloroquine/chemical synthesis , Chloroquine/pharmacology , Crystallography, X-Ray , Drug Resistance , Drug Screening Assays, Antitumor , Ferrous Compounds/chemical synthesis , Ferrous Compounds/pharmacology , Hemin/chemistry , Humans , Hydrogen Bonding , Hydrophobic and Hydrophilic Interactions , Metallocenes , Models, Molecular , Molecular Structure , Parasitic Sensitivity Tests , Plasmodium falciparum , Structure-Activity Relationship
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